Race 2012

Physiology of neuromuscular transmission 1 Anitha Shenoy
BASIC SCIENCE LECTURES
RACE 2012 Ramachandra Anesthesia Continuing Education


01 PHYSIOLOGY OF NEUROMUSCULAR TRANSMISSION
Professor Anitha Shenoy

Kasturba Medical College,
Manipal
Introduction Acetyl choline released from the nerve fibre crosses

the cleft and reaches the receptor. The postjunctional
Muscle relaxants are an integral part of modern
membrane also consists of sodium channels situated
general anesthetic techniques requiring endotracheal
perijunctionally. The acetyl choline receptor is a flower
intubation. Although intermediate acting drugs are
shaped structure with five petal like subunits. Each
in use today virtually eliminating the market for the
subunit is a protein molecule with definite configura-
longer acting drugs, neuromuscular blockade can be
tion. The acetyl choline receptor can take one of three
the cause of life-threatening problems due to residual
forms; the normal mature form, fetal immature form and
relaxant effect. It is therefore essential for the anes-
the abnormal form. The normal mature form has two
thesiologist to have a good understanding of the basic
alpha, one beta, one delta and one epsilon units and is
physiology and pharmacology and the factors that may
termed high conductance channel. The fetal form has
exist in pathological states.
a gamma unit instead of the epsilon unit and is a low
Anatomy and physiology of neuromuscular junc- conductance channel. The abnormal receptor has five
tion alpha 7 subunits.
The neuromuscular junction consists of the motor Acetyl choline released from the nerve ending
nerve fibre ending in a fray of fibrils on to the muscle crosses the cleft, reaches the receptor and combines
membrane. Each motor nerve divides into many fibrils with it. When both the alpha subunits are occupied
innervating several muscle fibres enabling contraction by acetyl choline, the channel opens and permits
of all the innervated units together in response to a passage of sodium across the channel. This sodium
nerve impulse. An electrical impulse originates in the influx produces depolarization of the muscle membrane
nerve cell and is transmitted to the nerve ending. The which then spreads across the entire membrane and
nerve ending contains acetyl choline synthesized and contraction occurs. The acetyl choline is released very
stored in vesicles. Acetyl choline is synthesized from quickly from the receptor and destroyed by acetyl cho-
acetate and choline in the presence of the enzyme linesterase present in the cleft to acetate and choline.
choline acetyl transferase in the nerve ending. These These are recycled into the nerve ending to produce
molecules are then packaged in vesicles some of which fresh acetyl choline.
are positioned near the synapse (readily releasable
Depolarising neuromuscular blockade
pool) and others in the cytoplasm (reserve pool). In
response to a stimulus, calcium ion channels in the Succinyl choline is the only clinically available
nerve ending open permitting entry of calcium into the depolarising muscle relaxant. The succinyl choline
nerve ending. This calcium influx triggers the docking molecule is two molecules of acetyl choline attached
of the acetyl choline vesicles with the nerve membrane back to back and hence behaves like acetyl choline
opposite the synapse and releases the neurotransmit- at the neuromuscular junction. It attaches itself to the
ter into the junction. acetyl choline receptor and produces depolarisation.
The main difference between their actions is that the
The nerve ending is separated from the muscle
action of succinyl choline is prolonged as it is not easily
membrane by a small distance called the cleft. The
destroyed like acetyl choline. Continued depolarisation
muscle membrane at the synapse is folded creating
results in what is termed ‘accommodation blockade’.
primary and secondary clefts. Acetyl choline recep-
This is better understood with a closer look at the so-
tors (nicotinic type) are situated at the top of the clefts.
dium channel itself.

The initial fasciculations seen with succinyl cho-

line are due to the effects of succinyl choline on the
prejunctional acetyl choline receptors causing repetitive
firing and release of neurotransmitter. These fascicula-
tions cause muscle pains postoperatively, prominently
seen in young and muscular males. Abolition or at-
tenuation of the fasciculations may be achieved by
using precurarisation (using a small dose, one-tenth
of intubating dose, of nondepolarising muscle relaxant
Figure 1: Sodium channels and their configurations:
3 min before injection of succinyl choline), self taming
a) The resting state b) Activated state c) Inactivated
(using a small dose, about one-tenth of intubating
state. v – Voltage dependent gate; t – Time depen-
dose, of succinyl choline 3 min before injection of the
dent gate.
full dose), prior injection of intravenous lignocaine, or
using a larger dose of thiopentone. None of these are
The acetyl choline receptor channel exists in three effective in all cases. Both precurarisation and self-
forms: a resting state, an active state and an inactive taming techniques are probably mediated through the
state (Figure 1). It has two gates inside it, one is a volt- block of prejunctional receptors. The intubating dose of
age dependent gate and the other a time dependent succinyl choline subsequently given must be increased
gate. In the resting state, the time dependent gate is (1.5 mg/kg as against 1 mg/kg without pretreatment)
kept open and the voltage dependent gate closed. if these techniques are used. Beware of bradycardia/
With the arrival of the electrical impulse, the voltage cardiac arrest that may be associated with self taming
dependent opens allowing sodium to pass through. (akin to second dose of succinyl choline) and pretreat-
The voltage dependent gate remains open as long as ment with atropine is advised. Precurarisation is thus
the electrical stimulus is present. However, the time a better technique. Occasionally, patients might feel
dependent gate closes soon and the channel goes weakness and diplopia even with the precurarisation
into an inactive state. The channel can be reactivated dose of nondepolarising muscle relaxant. In such
only after the membrane potential is reset when the cases, immediate induction of anesthesia is advised.
voltage dependent gate closes and the time dependent The effects of succinyl choline on the neuromuscular
gate opens again returning the receptor to its resting junction are terminated when the drug diffuses away
state. from the neuromuscular junction down a concentra-
Succinyl choline combines with the acetyl choline tion gradient into the plasma and gets metabolised by
receptor and produces continuous depolarisation. plasma cholinesterase.
Initially, both the time dependent and the voltage de- Nondepolarising (competitive) blockade
pendent gates are open but later the time dependent
gate closes and stops further passage of sodium ions. Nondepolarising muscle relaxants combine with
The voltage dependent gate continues to remain open the alpha subunit of the acetyl choline receptor. Even if
(depolarised state) as long as succinyl choline remains one of the subunits is occupied by the nondepolariser,
combined with the receptor (unlike acetyl choline, which it prevents acetyl choline from combining with both the
is swiftly metabolised). Thus, the receptor goes into an alpha subunits, thus preventing depolarisation. Thus,
inactivated state. The sodium channels at the junction for every two molecules of acetyl choline required to
and at the peri-junctional area remain inactivated and open the channel, one molecule of nondepolarising
the muscle becomes flaccid. This type of blockade muscle relaxant is sufficient to prevent opening of the
produced by succinyl choline is called Phase I block channel. The ratio of nondepolarising muscle relaxant
or ‘accommodation’ block. to acetyl choline required to affect the receptor is 1:2.
As the nondepolarising muscle relaxant gets metabo-
lised, there are a relatively larger number of acetyl cho-

line molecules available and depolarisation can take Channel block

place. This type of blockade is called competitive type
In this type of blockade, the drug binds to the
of blockade.
receptor either at the mouth preventing its opening
Abnormal actions on the neuromuscular junction (closed channel blockade) or inside the channel with
their actions increasing with repeated opening of the
Several drugs such as volatile anesthetics, pro-
channel (open channel or use dependent blockade).
caine and ketamine can affect neuromuscular trans-
Closed channel blockade is the likely mechanism of
mission not by their direct actions on the acetyl choline
prolongation of neuromuscular blockade by tricyclic
receptor but indirectly through the lipid matrix altering
antidepressants whereas open channel blockade is
binding characteristics of the receptor or affecting its
the likely mechanism for potentiation of blockade by
channel. The former is called desensitisation and the
antibiotics, quinidine, steroids or local anesthetics.
latter, channel blockade.
Phase II block
This type of blockade is known to occur with either
repeated boluses or prolonged infusion of depolarising
muscle relaxants. Development of phase II block de-
pends on dose of the drug, concurrent administration of
inhalation anesthetics and other drugs and the type of
muscle. In patients with atypical pseudocholinesterase,
phase II block can occur even with a single dose of suc-
cinyl choline. The causes could be prejunctional, where
in there is depletion of the neurotransmitter (block of
synthesis and release of acetyl choline), postjunctional
receptor desensitisation or effects on the sodium potas-
Figure 2: Various states of the nicotinic acetyl choline
sium ATPase pump. With prolonged depolarisation, so-
receptor. The top row shows (A) the acetyl choline
dium influx and potassium efflux continues and there is
receptor in the resting state, with the agonist near the
a disruption in the ionic composition of the membrane.
receptor, (B) agonists combined with receptor but chan-
Calcium also enters through the open channels and
nel not yet open and (C) with the channel open and
can cause distortion in the receptors. Neuromuscular
activated state. The bottom row shows (D) the receptor
monitoring during phase II block shows a picture akin
not combined with agonist but inactive (desensitised)
to nondepolarising blockade and there are instances of
and (E) with agonist and in desensitised state. All states
successful reversal with anticholinesterases. However,
of the receptor are said to be in dynamic equilibrium.
the reversal is not always predictable and it is advisable
Desensitisation not to attempt reversal with anticholinesterases.
In this type of blockade, the drug combines with Junctional and extrajunctional receptors
the receptor but does not result in opening of the chan-
The mature nicotinic acetyl choline receptor is
nel (Figure 2). It also prevents acetyl choline from acti-
always junctional receptor, i.e., it is situated only at the
vating the receptor. Thus, the receptor is desensitised
neuromuscular junction. The fetal, immature receptors
to the effects of acetyl choline. Both depolarisers and
differ in that they have one gamma subunit instead of
nondepolarisers can produce desensitisation. Other
the epsilon subunit. They are also distributed through-
drugs used during anesthesia such as volatile anesthet-
out the muscle membrane (Table 1). As the fetus grows
ics, local anesthetics, antibiotics, thiopentone, ketamine
and muscles become innervated, nerve growth factors
and even neostigmine can cause desensitisation.
(neuregulin, agrin and even insulin) released from the

nerve cell cause mature isoforms of the receptor to be tors. This explains why a denervated muscle resistant
synthesised and inserted into the junctional area of the to nondepolarisers (e.g., burns, upper and lower
muscle membrane. At birth, acetyl choline receptors motor lesions, prolonged immobilisation, prolonged
are present mainly at the neuromuscular junction. exposure to nondepolarising muscle relaxants). Since
there are so many channels available, the presence of
There is yet another acetyl choline receptor called
succinyl choline and even its metabolite, choline can
the alpha 7 receptor which is a pentamer consisting of
produce depolarisation, massive efflux of potassium
only alpha subunits. These are mainly extrajunctional,
and life-threatening hyperkalemia. This explains why
i.e., scattered over the muscle membrane but are not
a denervated muscle is sensitive to depolarisers. Such
excluded from the junction. Acetyl choline (or succinyl
a reaction may be seen in certain congenital muscle
choline) can bind to any of the alpha subunits and pro-
dystrophies also. Since the dystrophies may not be
duce depolarisation. Since the receptor contains five
apparent before the child is two years old, the risk
alpha subunits, even if three subunits are occupied by
of eliciting such an abnormal reaction in a child less
a nondepolariser, two more alpha subunits are avail-
than two years old (undiagnosed muscle dystrophy)
able for acetyl choline to bind and produce depolarisa-
is always present. That is the reason succinyl choline
tion. In a denervated muscle, there is a change in the
should not be used for intubation in children less than
receptor type from mature to immature receptors as
two years old unless a strong indication such as full
well as insertion of a multitude of the alpha 7 recep-
stomach exists.
Table 1: Comparison of mature and immature nicotinic cholinergic receptors
Mature receptor Immature receptor
Protein subunits 2 alpha, 1 beta, 1 delta and 1 2 alpha, 1 beta, 1 delta and 1
epsilon unit gamma unit
Half life 2 weeks 24 hours
Channel width Wider Narrow
Channel open time Short Long (2 – 10 fold longer)
Effect of depolarisers Less sensitive than immature One tenth to one hundredth of the
receptor dose may be sufficient for
depolarisation
Effect of nondepolarisers Sensitive (the drug is more More resistant than mature
potent) receptor
In the newborn, the postjunctional membrane has tanic stimulation or train-of-four stimulation is mediated
fewer folds, fewer receptors and the cleft between the through these prejunctional receptors. Nondepolarisers
nerve ending and the muscle membrane is wide. This block action of acetyl choline on these receptors and
is similar to that seen in myasthenia gravis (autoanti- show fade. Succinyl choline does not react with these
bodies against nicotinic receptors cause a reduction receptors and does not show fade.
in their number). Neonates are described as miniature
Antagonism of neuromuscular blockade
myasthenics. Both are very sensitive to nondepolaris-
ing muscle relaxants. The child is about two years old This is usually achieved using anticholinest-
when all the receptors are mature. erases, clinically used is neostigmine. Administration
of neostigmine prevents degradation of acetyl choline
Acetyl choline receptors are also present on the
by acetyl cholinesterase, allows its accumulation at
prejunctional nerve membrane and are morphologically
the neuromuscular junction and antagonizes non-
different from postjunctional receptors. They are alpha3
depolarising (competitive) neuromuscular blockade.
beta2 type (α3β2 type). The feedback mechanisms for
Cyclodextrins are other group of drugs currently avail-
release of acetyl choline are mediated through the
able (e.g., sugammadex) which act by direct binding
prejunctional receptors. The fade seen in response to ti-
by chemical interaction. These drugs are small, cyclic

polysaccharides synthesized from bacteria. It binds postjunctional occupation by nondepolarisers results

steroidal muscle relaxants with very high affinity and in fade. The appearance of fade depends on the extent
inactivates them. of nondepolarising neuromuscular block as well as the
frequency of tetanic stimulation. Tetanic stimulation is
Monitoring of neuromuscular blockade
very painful in the unanesthetised patient and is used
Neuromuscular blockade may be monitored us- clinically only with assessment using post-tetanic count
ing a peripheral nerve stimulator. The common modes under anesthesia.
used are the train-of-four, tetanic stimulation, post-
Post-tetanic stimulation: A tetanic stimulus (50 Hz for
tetanic stimulation and double burst stimulation. Depo-
5 s) followed by post-tetanic stimulation demonstrated
larising and nondepolarising muscle relaxants produce
post-tetanic potentiation with nondepolarisers and no
different patterns of neuromuscular blockade.
such response with depolarisers. Post-tetanic potentia-
Train of four: A series of four supramaximal stimuli at tion is due to increased mobilisation of acetyl choline
2 Hz are given over 2 s to a peripheral nerve and the following an initial decrease in acetyl choline release
responses of the muscle/s supplied by the nerve are from the prejunctional membrane.
observed clinically (visually and tactile response). All
Post-tetanic count (PTC): To assess profound depth
responses are strong and equal in height before neu-
of neuromuscular blockade (beyond 90% block), a te-
romuscular blockade. Train of four stimulation should
tanic stimulus is followed by single twitch stimulation at
not be repeated in more than once every 10 - 20 s.
1 Hz may be used. The number of responses to these
Nondepolarising block: The responses fade in height single twitches is counted. If none are present, signi-
with increasing doses followed by disappearance of fies 100% block. As neuromuscular blockade recovers,
the fourth, third, second and lastly the first response the number of responses increases. There may be
as 75%, 80%, 90% and 100% receptors are blocked. inter-drug variations in the time taken to recovery from
Thus, with increasing degree of block, a fade is seen. appearance of certain number of post-tetanic twitches.
The ratio of the height of the fourth response to the first Appearance of 8 – 12 responses corresponds to ap-
response may also be used to monitor the degree of pearance of the first twitch to the train-of-four response
neuromuscular blockade. The advantage of TOF ratio is with intermediate-acting muscle relaxants (atracurium
that a preoperative control is not required for assessing faster than vecuronium). A PTC of 0 may be aimed at
the degree of neuromuscular blockade. when no movement is desirable during surgery as in
Depolarising block: This is characterised by reduced ophthalmological or neurosurgery. Tetanic stimulation
twitch height of all four responses depending on the should not be performed more than once every six
dose. After an intubating dose of succinyl choline all minutes. Too frequent stimulation may actually result
four twitches disappear and with recovery, all four in local antagonism of neuromuscular blockade (due
responses gradually increase in height. There is no to increased mobilisation of acetyl choline). This may
fade. not reflect the extent of neuromuscular blockade in the
rest of the body.
Tetanic stimulation: A supramaximal stimulus is given
continuously for 5 s, (usually at 50 Hz). Normally, this Double burst stimulation: This consists of two short
kind of stimulus releases a large amount of acetyl bursts of 50 Hz stimulation separated by 750 ms.
choline and causes sustained contraction. This is Each burst may consist of two or three stimuli lasting
because the amount of acetyl choline released is in 20 ms. The tactile response to these two bursts is
excess of that required to produce effective contraction. assessed for presence of fade. Good correlation has
In the presence of nondepolarisers, a tetanic stimulus been found between TOF ratio and fade with double
causes increased release of acetyl choline and then burst stimulation. Tactile sensation of fade is better felt
its depletion. This prejunctional effect in addition to with DBS than train of four when the block is between
40 and 50%.

Different sites of monitoring and their signifi- Recommended reading

cance
1) Martyn JAJ. Neuromuscular physiology and pharmacol-
Different muscle groups have different degrees ogy. In: Miller RD, ed. Miller’s anesthesia. New York:
of sensitivity to muscle relaxants. Abdominal muscles, Churchill Livingstone; 2010.p.345-60.
upper airway muscles, corrugator supercilii muscles
2) Naguib M, Lien CA. Pharmacology of muscle relaxants
are most sensitive to muscle relaxants. Blockade at
and their antagonists. In: Miller RD, ed. Miller’s anesthe-
the corrugator supercilii correlates best with that at the
sia. New York: Churchill Livingstone; 2010.p.859-911.
laryngeal and abdominal muscles. Diaphragm is said
to be most resistant to muscle relaxants and although 3) Appiah-Ankam J, Hunter JM. Pharmacology of neu-
the onset of action of muscle relaxants is earlier in the romuscular blocking drugs. Continuing education in
diaphragm as compared to adductor pollicis muscle, anesthesia, critical care and pain. 2004; 4:2-7.
recovery is also earlier in the diaphragm. 4) Padmaja D, Mantha S. Monitoring of neuromuscular
junction. Indian J Anaesth 2002; 46:279-88.

Physiology of cerebral protection 9 Satyajeet Misra
01 PHYSIOLOGY OF CEREBRAL PROTECTION
Assistant Professor Satyajeet Misra

Sree Chitra Tirunal Institute for
Medical Sciences and Technology
Trivandrum
The objectives of this lecture will be to review the cardiac, vascular or orthopedic surgery), traumatic
factors contributing to focal and global ischemia within brain injury, acute stroke, severe systemic hypotension
the biochemical cascade and explain in detail about in extremes of age, cardiac arrest etc. Although the
the various protection strategies in the perioperative brain weighs only 2% of the body weight, it accounts for
period. 20% of the body’s oxygen consumption (Table 1). Most
of the cerebral metabolic rate for oxygen (CMRO2) is for
Review of the physiological variables
maintenance of neuronal activity, i.e. neurotransmis-
The brain is the organ most vulnerable to ischemic sion (approx. 55%) with the rest of oxygen being utilized
injury, especially in the perioperative period. Anesthesi- for basal metabolic activity of the neuronal cells (45%).
ologists may be faced with a number of situations where In the healthy state, cerebral blood flow (CBF) is tightly
the brain is at risk, for e.g., surgical procedures (neuro, coupled to the CMRO2 (neurovascular coupling).
Age MAP (mm Hg) ICP (mm Hg) CBF (mL/100 CMRO2
gm/min) (ml/100gm/min)
Premature 35-45 <3 5-30 1-2
Newborns 45-55 2-5 30-40 2-3
Infants 70-75 3-7 50-80 4-5
School children 75-80 5-12 85-100 3.5-5
Adults 90-100 8-15 45-50 3.5
Table 1: Age dependent physiological variables. Note the tight coupling of CBF to CMRO2 which is
highest in school children
Local by-products of metabolism like K+, H+, lac- ischemia, the CBF is held constant between a MAP of
tate, adenosine etc may play a part in flow-coupling. In 50-150 mm Hg, principally by a myogenic mechanism
addition, glutamate, which is released with excessive of the smooth muscles of the cerebral arterioles (with
neuronal activity results in synthesis and release of decrease in MAP, the cerebral vasculature dilates
nitric oxide (NO), which is a potent cerebral vasodilator and with increase in MAP, the vasculature constricts;
and plays an important role in flow coupling. Gray mat- mathematically, flow = pressure/resistance) (Figure 1).
ter, where the neuronal cells and synapses are located This phenomenon is lost in disease states, where the
has a blood flow of approximately 60-80 mL/100gm/ circulation becomes pressure-passive (i.e. hypotension
min, while, subcortical white matter, which contains causes vascular collapse and hypertension causes
the fibre tracts has a blood flow of 20-25 mL/100 gm/ more vasodilatation). The neurogenic regulation of CBF
min. is by cholinergic, adrenergic and VIP-ergic systems of
extra and intra-axial origin. To summarize, a change
The cerebral perfusion pressure (CPP) is deter-
in cerebral metabolism but not perfusion pressures will
mined by the difference of the mean arterial pressure
alter the CBF in the normal brain. Other physiological
(MAP) and the intracranial pressure (ICP). Autoregula-
variables affecting CBF are the PaCO2, PaO2 and he-
tion is an important phenomenon of the cerebral vascu-
matocrit and anesthetics.
lature, wherein, in adults without focal or global cerebral

baseline) and PaO2 > 300 mm Hg results in a 10-30%

reduction in CBF. Hematocrit, the most important factor
of blood viscosity can also affect CBF. In healthy sub-
Newborns ~ 10ml/100g/min jects, variation of hematocrit within the normal range of
Infants and school children ~ 50-100ml/100g/min 33-45 % causes minimal changes in CBF. In the setting
Cerebral Blood Flow
Adults ~ 45ml /100g/min

of ischemia, a hematocrit level of 30-34% is recom-
mended to optimize CBF. Anesthetics also affect CBF
in complex manner (Table 2). In general, intravenous
anesthetics, with the exception of ketamine, generally
preserve the flow-coupling and reduce both CBF and
CMRO2. Although volatile anesthetics cause cerebral
New borns ~ 30 mmHg New borns ~ ? mmHg vasodilatation, below 1 MAC they generally preserve
Adults ~ 60 mmHg Adults ~ 160 mmHg
the flow-coupling by causing a decrease in CMRO2
with minimal increases in CBF. However, > 1.5 MAC,
Mean Arterial Pressure the predominant effect is vasodilatation with increases
in CBF which coupled with decreases in CMRO2, may
Figure 1: Cerebral autoregulation. Since pressure lead to luxury perfusion (perfusion in excess of require-
= flow x resistance, therefore, for flow to remain ment).
constant, as pressure changes, so does resistance.
In intact autoregulation, resistance changes in
the same direction as pressure, i.e., as MAP goes
up, so does the vascular resistance and vice-
versa. In impaired autoregulation, it changes in
the opposite direction, i.e. with increase in MAP,
resistance decreases and the cerebral vasculature
dilates and thus results in increase in CBV and ICP.
Conversely, when MAP falls, the vessels collapse
leading to a decrease in CPP. In newborns, upper
limit of autoregulation is not known.
CO2 vasoreactivity refers to the vasoconstriction
of cerebral vessels to hypocapnia and vasodilatation
to hypercapnia (opposite to the effect of CO2 on the
vasculature in other organs). Between 20-80 mm Hg of
PaCO2, CBF is affected linearly by changes in PaCO2
(Figure 2). CO2 vasoreactivity may be abolished in Figure 2: Linear reactivity of the cerebral vascu-
disease states, though autoregulation is usually im- lature to arterial CO2, i.e. as the PaCO2 increases,
paired first. Unlike PaCO2, a change in PaO2 between the cerebral vasculature dilates and vice-versa.
50-300 mm Hg does not cause significant changes in This relation is usually preserved even in impaired
CBF. However, hypoxemia (arterial PaO2 < 50 mm Hg) autoregulation, which formed the basis for earlier
results in an exponential increase of CBF (upto 400% of use of hypocapnia to constrict the cerebral blood
vessels to decrease ICP.

Drug Vessel tone CPP CBF CMRO2 Autoregulation CO2

reactivity
Propofol Vasoconstriction +/- - - Intact Intact
Thiopentone Vasoconstriction +/- - - Intact Intact
Ketamine Vasodilatation - + + Intact Intact
Dexmedetomidine Vasoconstriction - - - Intact Intact
Isoflurane Vasodilatation - + - Impaired Intact
Sevoflurane Vasodilatation - + - Impaired Intact
Desflurane Vasodilatation - - - Impaired Intact
Table 2: Effect of anesthetics on CPP, autoregulation and CO2 reactivity. +/- denotes no change,+
denotes increase, - denotes a fall and (+) denotes minimal rise and (-) denotes minimal fall. Note that
volatile anesthetics cause cerebral vasodilatation and cause impaired autoregulation, thus decreasing
CPP, but CO2 reactivity is still preserved. Note that volatile anesthetics tend to uncouple
flow-metabolism > 1.5 MAC.
The ICP, which is one of the important determi- tracranial volume cause minimal changes in ICP.
nants of the CPP, is mainly influenced by the volume However, increased elastance (change in pres-
of the various intracranial compartments (brain tissue sure/ change in volume) or decreased compliance
volume 80%, blood volume 10% and cerebrospinal (change in volume/change in pressure) is seen
fluid volume 10%) (Figure 3). According to the Munroe- in the ischemic brain with minimal alterations in
Kellie hypothesis, since the cranium has a fixed volume, volume causing massive increases in ICP (Munro-
an increase of any one component has to be balanced Kellie doctrine).
by a decrease in the volume of another component, or Disruptive consequences of focal and global ce-
else the ICP will increase. In general, the relation of rebral ischemia
cerebral blood volume (CBV) (approx. 5 ml/100 gm) is
parallel to changes of CBF. However, the magnitude of Neuronal cells are near obligate glucose users.
change in CBV is less than the magnitude of change In the presence of oxygen, glucose undergoes me-
in CBF. In addition, CBF and CBV may vary indepen- tabolism to pyruvate and this generates 38 moles of
dent of each other in ischemia, where CBV increases adenosine tri-phosphate (ATP)/mol of glucose. ATP
significantly whereas CBF is decreased. is a high energy phosphate that in turn is utilized by
the mitochondria for performing the cellular and meta-
bolic functions of the neuronal cells. In the absence
of oxygen, neuronal cells switch over to anaerobic
metabolism which results in glucose being metabolized
to lactate with a limited generation of ATP (2 moles/
mol of glucose). This ATP is insufficient to meet the
high energy requirements of neuronal cells and thus,
the ATP stores are quickly depleted during ischemia.
During ischemia, 3 main cellular events occur. Initially,
a large efflux of K+ from the cells occurs with influx of
Na+ & Cl- into the cells. This results in depolarization
of neuronal cells (anoxic depolarization). The second
event is large releases of the excitatory neurotransmit-
ter glutamate due to the anoxic depolarization. The
third event is activation of amino-3-hydroxy-5-methyl-
Figure 3: Intracranial pressure-volume elastance 4-isoxazole proprionic acid (AMPA) and n-methyl-d-
relationship. In the normal brain, changes in in- aspartate (NMDA) receptors due to further neuronal
depolarization by the high glutamate levels. These In the immediate period following an acute focal
receptors further increase the intracellular concentra- ischemic injury, there exist 3 distinct zones within the
tions of sodium and calcium. Glutamate also increases brain (Figure 4). The first is the ischemic core where
the release of calcium from intracellular stores, and the the cells are irreversibly dead (CBF < 6 ml/100 gm/
damage resulting from supranormal concentrations of min). The zone next to the ischemic core is the pen-
glutamate is called excitotoxicity. umbra (“almost dark”), where, the cells are stunned but
potentially viable (6-15 ml/100gm/min). The last is the
High cytosolic Ca2+ (increased influx, decreased
penlucida (“almost light”), where the cells are able to
efflux and release from other intracellular structures
tolerate flows of 15-23 ml/100gm/min without manifest-
like endoplasmic reticulum) triggers a number of events
ing any long term sequelae of the ischemic episode.
that lead to ischemic damage, notably by increasing
The aim of neuroprotection is to rescue the cells in the
the activity of proteases and phospholipases, which
penumbra /penlucida zone by targeting the various
in turn increase the level of free fatty acids such as
putative pathways involved in neuronal cell death.
arachidonic acids and free radicals. Free radicals
damage proteins and lipids and further interfere with Neuroprotection
membrane function. Continued buildup of lactate and
By definition, treatment initiated before onset of
H+ ions worsen the intracellular environment and result
ischemia, to modify intra-ischemic cellular and vascular
in more free radical formation. During reperfusion, free
biologic responses to deprivation of energy supply so
radicals are generated due to oxidation of arachidonic
as to increase the tolerance of neuronal cells to the
acid which results in intense vasoconstriction which
ischemic insult is neuroprotection. In contrast, neuro
worsens the ischemic insult. The subsequent cellular
rescue is the treatment initiated after occurrence of an
death and necrosis initiates an inflammatory cascade
ischemic insult in order to mitigate the secondary ef-
which worsens the neuronal damage. In addition, there
fects of the primary event. Most of the neuroprotection
also occurs a genetically programmed cell death result
practiced in the clinical scenario actually represents
known as apoptosis, wherein cell death occurs without
neuro rescue. Such treatment may be divided into non-
lysis. Proteins that lead to apoptotic cell death are
pharmacological and pharmacological treatment.
called caspases and blockade of caspases has been
shown to block apoptosis. (i) Non-pharmacological neuroprotection
Since the outcome of ischemic brain injury can
be worsened by hypotension, hypovolemia, hy-
poxia, hypocapnia or anemia, maintenance of
physiological variables within normal limits is the
goal.
(a) MAP: Since the ICP rises in the injured brain,
the target should be to maintain MAP so as
to provide a CPP of at least 60 mm Hg. In
the absence of invasive ICP monitoring, it is
reasonable to maintain a MAP of around 90
Figure 4: Concept of ischemic penumbra zone. mm Hg (systolic blood pressure of 120 mm
The core represents CBF below a critical level (< 6 Hg). Excessive increases in MAP should be
ml/100 gm/min), where cell death is inevitable. This avoided as this has been found to increase
is surrounded by an area called “penumbra” where the incidence of ARDS. In case the ICP is
the cells are functionally impaired but potentially monitored and found to be high (> 20 mm
viable (CBF between 6-15 ml/100 gm/min). Over Hg), additional measures like drainage of
time, the ischemic core grows at the expense of CSF, decompressive craniectomy etc may
the penumbra. be considered to improve the CPP. Conduct

of anesthesia should be smooth with particu- compared to those resuscitated with 100%
lar care to avoid fluctuations of blood pres- O2. Thus, the goal of mechanical ventilation,
sure during periods of induction, emergence, if instituted should be to maintain a PaCO2
application of skull pins (in neurosurgery) of approximately 35 mm Hg and a SpO2 of
etc. > 95% with the lowest FiO2.
(b) Ventilation: Although hypocapnia had been (c) Glucose: While deprivation of glucose in
used in the past in the belief that some the presence of oxygen results in neuronal
amount of cerebral vasoconstriction limits necrosis, its presence in the absence of
the CBV and thus decreases ICP, this de- oxygen is even worse. Although the ratio-
crease in CBV and ICP is at the expense of nale for this paradox is unclear, it is now
decreased CBF and decreased perfusion. believed that in the absence of oxygen,
In addition, vessel calibre is reset during glucose undergoes anerobic metabolism,
prolonged hypocapnia with return of ICP with generation of lactate resulting in intra-
to previous values. Finally, normocapnia cellular acidosis which amplifies the severity
after hypocapnia produces an exaggerated of the deleterious cascade initiated by the
increase in vessel diameter with increase ischemic insult. Whether the hyperglycemia
in CBV and ICP. In the event hypocapnia is a stress response to neuronal injury is not
(PaCO2 of 28-30 mm Hg) is required, for e.g. known, but smaller infarct size has been
in impending tentorial herniation or in severe observed in animal models of tight sugar
parenchymal edema, it is preferable to have control. In humans too, better neurological
a monitor to measure the cerebral perfusion outcome has been seen in stroke patients
like SjVO2 or near infrared spectroscopy with admission hyperglycemia in whom the
(NIRS) or brain tissue oximetery (PbO2), so blood sugar was tightly regulated. As such,
that critical decreases in CBF that further normoglycemia (blood glucose < 130 mg/
worsen tissue ischemia can be prevented. dL) should be the goal.
Regarding oxygenation, it makes sense that (d) Hemoglobin: Since substrate delivery
since O2 delivery is the primary failure, in- is limited during an ischemic attack, it is
creasing the oxygen content of the ischemic important to optimize hemoglobin concen-
tissues should improve outcome. In fact, trations to improve oxygen delivery. While
cerebral tissue hypoxia is an independent high hematocrit is definitely harmful as it
predictor of neuronal cell death. In animal promotes capillary sludging due to increased
models of focal ischemia, both normobaric viscosity and decreases flow, lower levels
as well as hyperbaric hyperoxemia have of hematocrit may compromise oxygen
been associated with smaller infarct sizes. delivery even if they improve flow second-
However, canine models of global ischemia ary to the improved rheology. Therefore, a
have been associated with a worse outcome target hematocrit of approximately 30-34%
with hyperoxemia presumably due to greater should be maintained in patients at risk or
peroxidation of lipids and greater genera- with neurological injury.
tion of free radicals during the reperfusion
(e) Temperature: One of the important aspects
phase. In humans, no recommendations
of neuroprotection in the last decade has
exist for the use of hyperbaric oxygen for
been the re-emergence of hypothermia.
neuroprotection and data regarding the use
In the past, the benefits of hypothermia
of normobaric hyperoxemia is limited. In
were attributed solely to a reduction in tis-
neonates resuscitated with 40% O2, there
sue metabolism and thus, the goal was to
was quicker recovery of APGAR scores as

decrease the temperature as much as pos- infection. The inflammatory reaction in the
sible, often to deep hypothermia (18-200C). brain is in contrast to the systemic immuno-
However, the deleterious effects of deep suppression that is seen in patients of acute
hypothermia like arrhythmias, coagulopathy, stroke, who have increased risk of infection
infections precluded any advantage vis-à-vis like pneumonia etc. Thus, strict infection
the effects of reduction in temperature de- control by adherence to aseptic techniques
pendent metabolism. But continued animal and proper and rationale use of antibiotics
experiments clearly paved the path for use of is often warranted in these patients.
mild-moderate hypothermia (32-350C) as an
(ii) Pharmacological neuroprotection
armamentarium in neuroprotection. This was
due to the fact that apart from decreasing tis- Traditionally, pharmacological neuroprotection
sue metabolism, mild-moderate hypothermia has been achieved with anesthetics. The rationale
was found to decrease the inflammatory for this is simple. By decreasing the neurotrans-
mediators associated with ischemia. More mitter activity, anesthetics tend to decrease the
importantly, this was achieved without the CMRO2 and thus, enhance the ability of the
harmful effects of severe hypothermia. The neuronal cells to withstand ischemia. What is
greatest benefit is seen in out-of-hospital important to understand is that neurotransmitter
comatose survivors of cardiac arrest due activity only accounts for 55% of CMRO2 with
to ventricular fibrillation and in neonatal the remaining 45% due to the intrinsic metabolic
hypoxic-encephalopathy. Results in trau- activity of the neuronal cells. Thus, even at burst
matic brain injury have not been very en- suppression doses of the anesthetics (i.e. cortical
couraging and the practice of hypothermia electrical silence or isoelectric EEG), the maximal
in the intraoperative mileau especially in suppression of CMRO2 is not more than 50%,
intracranial aneurysm surgery has not because metabolic activity is still ongoing (this is
shown to be of benefit. Nevertheless, while suppressed only by hypothermia). The second
mild-moderate hypothermia may be applied limitation is while the rationale for neuroprotection
in certain situations, it is more important to with anesthetics is attractive, most of the benefits
prevent hyperthermia (core temp. > 370C) are seen in focal (e.g. acute stroke, transient oc-
by use of analgesics, antipyretics etc, as all clusion of MCA etc) but not global ischemia (e.g.
the deleterious processes of ischemia are cardiac arrest).
accelerated due to hyperthermia.
The third and the most important limitation is that
(f) Positioning: A 300 head up position often the benefits of anesthetics have been demon-
improves venous drainage and is helpful in strated in the in-vitro or in the experimental animal
reducing ICP. However, exaggerated eleva- lab environments, but have not been conclusively
tions of the head should be avoided as it can demonstrated in humans. Finally, none of the an-
result in pooling of blood in the extremities esthetics have been shown to be of post-ischemic
with a consequent decrease in the perfusion benefit even in experimental animals, i.e. there
pressures. Similarly endotracheal tubes was no benefit when the anesthetic agent was
should be secured by taping and not tying as administered after ischemia. Thus, pharmaco-
it can obstruct venous return from the head logical neuroprotection continued to evolve with
and neck.
investigators looking at non-anesthetic agents as
(g) Infection control: Most patients with well. This review will encapsulate both anesthetic
ischemic neuronal injury are susceptible to as well as non-anesthetic pharmacological neu-
roprotection.

Anesthetic neuroprotection CMRO2 and by an anti-apoptotic mechanism, but

the doses used in the experimental lab are much
(a) Barbiturates: Barbiturates have been used
higher than what is clinically used.
for more than 30 years for pharmacological
neuroprotection. Main action of barbiturates is (c) Volatile anesthetics: Most of the recent work
by decreasing the neurotransmitter activity and of anesthetic pharmacological neuroprotection
thus CMRO2. In animal models of focal ischemia, is focussed on volatile anesthetics. There are
barbiturates have been found to be beneficial. several attractive reasons for this. Experimental
However, this benefit has not been demonstrated work with isoflurane and sevoflurane has shown
in models of global ischemia. The main problem of that volatile anesthetics act through the pathway
barbiturate coma in humans is two-fold. First, the of “anesthetic preconditioning”. Simply put, they
dose that is required for isoelectric EEG hinders precondition the neuronal cells in such a manner
with the neurological assessment of patients, that the cells are able to withstand a more lethal
in addition to prolonging sedation and delaying period of ischemia. In essence, they increase
recovery. Second, these doses compromise the the intracellular concentration of Ca2+ to a small
MAP and this in turn may lead to worsening of the degree by acting on IP3 receptors. This sub acute
intra-neuronal ischemic mileau. Modified dose of increase in Ca2+ concentrations activates vari-
thiopentone for neuroprotection is a loading dose ous intracellular signal pathways which encode
of 5-10 mg/kg followed by an infusion dose of 3-5 protective genes. Thus, the cell memorizes this
mg/kg/hr with maintenance of hemodynamics by event. Subsequent massive increases in intrac-
volume infusion or inotropic support. Probably by ellular Ca2+ during an ischemic episode brings
reducing the frequency of seizures, thiopentone into play the protective factors encoded during
decreases the ICP and thus cerebral edema. the earlier exposure to the volatile anesthetics
and prevents apoptosis, necrosis and cell death.
(b) Other hypnotics: Propofol, etomidate, ketamine
Therefore, apart from their effects on decreasing
have all been tried as anesthetic neuroprotection
synaptic activity, volatile anesthetics regulate the
but are quite limited in their efficacy. Propofol
intracellular concentration of calcium and limit the
works in a manner similar to thiopentone and
ischemic damage.
reduces the CMRO2 by reducing synaptic neu-
rotransmission. In addition, propofol is an anti- Both isoflurane and sevoflurane have been shown
oxidant and has some free radical scavenging to be of benefit in experimental animals with focal
action and thus, is the only hypnotic that displays neurological injury; in the clinical scenario, sevo-
some post-ischemic benefit in laboratory animals, flurane would be expected to be a better choice
although this has not been seen in humans. given the fact that it causes the least increase in
However, there are no dose-dependent studies of cerebral vasodilatation. In addition, volatile anes-
propofol in the setting of neuroprotection. Etomi- thetics have been shown to have anti-apoptotic
date is not used for neuroprotection as evidence properties. One important consideration in the
suggests that it may inhibit NO synthase and thus use of volatile anesthetics for neuroprotection is
worsen the ischemic injury. Although Ketamine that higher doses (> 1.5 MAC for isoflurane) tend
is a potent glutaminergic inhibitor at the NMDA to be associated with a worse outcome due to
receptor level (NMDA receptor antagonist), there post-ischemic seizures, hypotension etc as com-
is no evidence to suggest that it may improve pared to lower doses (1-1.5 MAC for isoflurane).
outcome after neurological insult. In fact, there are Xenon is an inert gas that acts as an inhalational
no established reports of dose-related neuropro- anesthetic (MAC of 1 achieved with an inspired
tection even in experimental animals. Lidocaine concentration of 70-90%). Xenon has also been
also has been shown to be of limited efficacy in found to precondition the brain and provide neu-
providing neuroprotection principally by reducing roprotection; the principal site of action is believed

to be NMDA receptor antagonism. It has been and others showing no benefit. In clinical trials of
shown to be of some post-ischemic benefit also, the L-type Ca2+ blocker, nimodipine in patients
i.e., neuroprotection has been demonstrated with acute ischemic stroke and aneurysmatic or
when xenon is administered after an ischemic traumatic SAH, a favourable outcome is seen only
episode. However, optimal dose-response stud- if administration of nimodipine commences within
ies are not available and the agent is very costly. the first 12 hours following onset of symptoms.
Experimental use with helium seems encourag- Problems of Ca2+ channel blockers include in-
ing. Nitrous oxide is not used for neuroprotection duced arterial hypotension which may potentially
as it is associated with increased ICP and CBV. reverse any benefit in terms of neuroprotection.
Non-anesthetic neuroprotection (c) Erythropoietin: Erythropoietin is expressed in
many areas of the brain including the cortex,
Because so many putative processes are involved
hippocampus, internal capsule with its receptors
in the ischemic cascade, agents used for non-anes-
being expressed by neuronal cells. Hypoxia or
thetic pharmacological neuroprotection are intended
ischemia is an important driving force behind the
to target specific processes in the cascade. However,
expression of erythropoietin, suggesting that it is
most of the trials are abandoned and very few agents
a part of the self regulatory mechanism to mitigate
are used clinically. This summary will only focus on
the ischemic injury. Multiple animal studies of focal
the most relevant agents with a brief mention of the
and traumatic neuronal ischemia have confirmed
others.
that systemic application of erythropoietin stimu-
(a) NMDA receptor antagonists: Since activation of lates neurogenesis and activates anti-apoptotic,
NMDA receptors by glutamate leading to increase anti-oxidant and anti-inflammatory signalling. A
in intracellular Ca2+ plays a key role in amplifica- single centre study investigating 80 patients with
tion of the ischemic cascade, targeting the NMDA aneurysmatic SAH has found that 90,000 IU of
receptor is an attractive option. Other than mag- recombinant erythropoietin seemed to decrease
nesium however, most of the other NMDA antago- the severity of vasospasm and the incidence of
nists have been shown to be of no benefit and delayed cerebral ischemia.
may even cause harm. Apart from NMDA receptor
(d) Glucocorticoids: Proposed mechanisms of
antagonism, magnesium also decreases entry of
glucocorticoids in ischemic brain injury is by free
calcium into cells via a voltage gated mechanism.
radical scavenging and inhibition of membrane
In addition, vasodilatation may provide some
stabilization. No evidence of benefit has been
benefit in post SAH vasospasm. Despite this, a
shown in patients with global ischemic arrest and
landmark trial of magnesium sulphate infusion in
insufficient data exists in focal ischemic arrest.
patients with acute stroke failed to detect a benefit
Furthermore, animal studies have clearly shown
in terms of improved outcome, though a later trial
that glucocorticoids increase plasma glucose con-
in patients with aneurismal SAH demonstrated a
centrations in global ischemia and thus may cause
lower incidence of vasospasm as well as a lower
harm. Some beneficial evidence of Methylpred-
incidence of delayed ischemic complications in
nisolone has been demonstrated in patients with
those patients with vasospasm.
acute traumatic spinal cord injury when treatment
(b) Ca2+ channel blocker: Proposed mechanism of has been initiated early (< 8 hours) with duration
neuroprotection by Ca2+ channel blocker include of 48 hours.
cerebral vasodilatation, prevention of vasospasm,
(e) Statins: Statins are HMG CoA reductase inhibi-
reduced intracellular Ca2+ influx and modulation of
tors which, apart from their lipid lowering action,
free fatty acid metabolism. However, the results of
have a variety of “pleiotropic” actions that include
animal models are rather contradictory, with some
attenuation of vascular inflammation, improved
studies showing benefit following focal ischemia

endothelial cell function, stabilization of athero- formation of peroxynitrite and hydroxyl ions and
sclerotic plaques and inhibition of platelet aggre- releases NO in cytotoxic concentrations. Lubelu-
gation. Despite its proven efficacy in cardiac sur- zol, is an S-isomer of 3,4 di-fluroro-benzothiazole
gery, efficacy of statins in treating aneurysmatic that down regulates the glutamate activated NOS
SAH remains equivocal and is not recommended pathway and thus has been found to limit infarct
at this point of time. size in animal models of ischemia but these
results have not been validated by a Cochrane
(f) Antiepileptics: Phenytoin and fosphenytoin are
meta-analysis of 5 trials on 3510 stroke patients
used to decrease the frequency of post-ischemic
on either functional outcome or mortality in Lube-
seizures which may worsen the ICP and the cel-
luzol treated patients.
lular edema. In addition, fosphenytoin also has
some Na+ channel blocking action that limits the (i) Anti-excitotoxicity, anti-inflammatory and
entry of Ca2+ into cells. anti-oxidant interventions: Glutamate and
aspartate are known excitatory amines which
(g) Osmodiuretics: According to the “Lund” con-
result in increase in intracellular Ca2+ concen-
cept, autoregulation is impaired in the injured
trations. Infusion of competitive NMDA recep-
brain and thus, instead of increasing the MAP
tor antagonist selfotel has been shown to limit
to maintain CPP, the ICP should be reduced
infarct size in animal models. Trials with AMPA
to maintain CPP. Both mannitol and hypertonic
receptor antagonists are mostly abandoned due
saline (7.5%) are used to decrease the ICP by
to concerns of safety. Similarly, till date no trials
decreasing the CBV and promoting absorption
have been conclusively able to demonstrate the
of CSF, by creating an osmotic gradient in the
utility of anti-inflammatory agents in patients with
plasma which helps in mobilization of extracellular
neuronal injury. No clinical benefit of anti-oxidant
fluid across the gradient. In addition, mannitol is
therapy has been demonstrated in patients with
also a free radical scavenger. Plasma osmolarity
ischemic neuronal injury. Phase III clinical trials
should not be increased beyond 320 mOsm/L as
with the non-glucocorticoid aminosteroid tiralazad
it may precipitate acute tubular necrosis in the
mesylate, a potent inhibitor of oxygen free radical
kidney. Concerns of rebound hypertension after
induced lipid peroxidation failed to show any neu-
discontinuation of mannitol exist in the presence
roprotective benefit in patients with acute ischemic
of defective blood brain barrier or for treatment >
injury due to SAH, acute stroke or traumatic brain
4 days. Hypertonic saline has the advantage of
injury.
“smaller volumes” and more consistent decreases
in ICP as compared to mannitol. (j) Calpain and Caspase inhibitors: Calpains are
proteases that break down and digest cell pro-
(h) Nitric oxide: NO is a messenger molecule that
teins, i.e. cause necrosis. Basically Calpain is an
affects a variety of intracellular processes and is
inactive enzyme that becomes active during times
produced during conversion of L-Arginin to citrullin
of stress. Blocking the activity of this enzyme by
by the enzyme NO-synthase (NOS). Three iso-
inhibitors is more welcome than blocking gluta-
forms of NOS have been indentified; constitutive
mate which is required by the brain in minimal
NO-synthase isoforms I (neuronal NOS, nNOS)
concentrations. Calpain inhibitors have been used
& III (endothelial NOS, eNOS) are present in neu-
within a window period of 3-6 hours following
rons, astrocytes and endothelial cells, whereas
ischemic neuronal insult. Caspases are a family
inducible NOS (iNOS) is present in macrophages
of proteases that signal apoptosis or programmed
and leucocytes. During ischemic conditions, NO
cell death. Inhibition of caspase-3 (“killer enzyme”)
exerts both positive as wells as negative effects on
by minocycline has been shown to be of some
neuronal function. eNOS dilates cerebral vessels
benefit in animal models of neuronal ischemia.
and improves CBF, whereas iNOS contributes to

(k) Hormones: Difference in outcome of traumatic may be carried out as late as 6 hours after a focal isch-
brain injury between men and women stimulated emic episode and upto 2 days after a global ischemic
research into sex hormones. Both estrogen and episode.
progesterone offer neuroprotection by anti-apop-
Conclusion
totic and anti-oxidant properties and possibly by
decreasing excitotoxicity (progesterone). A holistic approach is required to manage patients
at risk of ischemic encephalopathy. Since numerous
(l) Ischemic pre and postconditioning: The con-
targets exist in the pathophysiological cascade of focal
cept behind ischemic preconditioning is that a
and global cerebral ischemia, no one treatment has
sub-lethal brief period of ischemia will “condition”
been found to be superior to another. But because so
the neuronal cells to a lethal ischemic insult. First
many potential pathways exist, it also gives the care
seen in the myocardium, this phenomenon has
provider the opportunity to target multiple variables in
been documented in the brain as well. Shortly af-
order to optimize outcome. Since most of the pharma-
ter “preconditioning” (early preconditioning which
cological factors in neuroprotection have not trans-
starts within minutes) or after a delay (delayed
lated into acceptable standards of care, it becomes
preconditioning which starts after hours to days),
even more imperative for the physician to control and
the brain develops tolerance towards the same or
optimize the physiological variables that could affect
even a different ischemic insult. In the precondi-
functional neuro outcome and patient morbidity and
tioning cascade, transcription factors are activated
mortality.
that ultimately modulate gene expression. This
leads to synthesis of new proteins or modification Thus, the focus should be on maintaining normo-
of existing proteins that act as effectors in enhanc- tension, normovolemia, normoglycemia, normoxia, nor-
ing the resistance of neurons to ischemia. Thus, mocapnia and preventing hyperthermia and infections.
tolerance induced by preconditioning affects Although nimodipine is useful in aneurysmatic SAH,
various functions like metabolic, immunologic, no convincing recommendation exists for magnesium
membrane ion-channel activity etc. This in turn and statins as neuroprotectants. The use of steroids
minimizes damage, improves substrate delivery and hypothermia and other measures like triple- H
and energy utilization during an ischemic event. therapy (hypertension, hypervolemia and hemodilution
in intracranial aneurysm surgery) and recombinant
Classical preconditioning has been tried with an-
erythropoietin are not indicated in patients at risk for
esthetic agents, molecules like glutamate or caspase,
cerebral ischemia in the perioperative period.
inflammatory cytokines and nicorandil (K+ channel
opener). References
In the clinical context, transient ischemic attacks 1. Fakuda S, Warner DS. Cerebral protection. Br J An-
(TIA) is analogous to ischemic preconditioning and aesth 2007;99:10-7
would be expected to provide a benefit against sub- 2. Klein KU, Engelhard K. Perioperative neuroprotection.
sequent stroke in terms of reduced severity. However, Best Pract Res Clin Anaesthesiol 2010;24:535-49
recent clinical studies have not been able to demon-
3. Sturgess J, Matta B. Brain protection: current and future
strate an improved outcome in stroke patients with a
options. Best Pract Res Clin Anaesthesiol 2008;22:167-
prior history of TIA.
76
Postconditioning refers to conditioning the cell
4. Vincent JL, Berré J. Primer of medical management of
after the actual ischemic event and is achieved by slow
severe brain injury. Crit Care Med 2005; 33: 1392-9
intermittent reperfusion of tissues after opening up of
an occluded vessel; this has been shown to reduce the 5. Knowlden P, Hunt K. Clinical neuroprotection and
infarct size after experimental stroke. Postconditioning secondary neuronal injury mechanisms. Anesthesia
and Intensive Care Med 2008;9:184-6

Respiratory Physiology and Anesthesia 19 Pankaj Kundra
01 RESPIRATORY PHYSIOLOGY AND ANAESTHESIA
Professor Pankaj Kundra

J.I.P.M.E.R.
Pondicherry
It is interesting to note how anaesthesia can af- • Influences on respiratory centres (Figure 1)
fect respiration in a spontaneously breathing patient.
ο Cortical influences: Voluntary controls:
However, balanced anaesthetic techniques that involve
conscious decisions to change the rate and
muscle paralysis are commonly employed. To under-
depth of breathing associated with speaking,
stand the effect of anaesthesia on respiration requires
singing, coughing, etc.
understanding of normal respiratory physiology which
includes the integration of respiratory control through ο Neural influences:
respiratory centres, chemoreceptors, upper airway (a) Medullary rhythmicity centre with its auto-
and interplay of airway pressures and muscles (lung rhythmic inspiratory and expiratory neurons
mechanics). sets the basal ventilation rate adjusted to the
Normal respiratory physiology level of activity and metabolic demands of
the body at any given moment.
• Respiratory centres control of breathing:The
ventral respiratory group (VRG) and the dorsal (b) Pontine respiratory centre neurons limit
respiratory group (DRG) within the medullary inspiratory duration by sending inhibitory
rhythmicity area cooperate to establish the pattern signals to the medullary rhythmicity area
for spontaneous ventilation and basal rate of ven- reducing duration of inspiratory impulses
tilation which may be adjusted by impulses from causing shorter cycles which increases
related respiratory control centres in the pons; the ventilation rate; these pontine respiratory
ventral respiratory group (VRG) contains both in- neurons receive input from higher brain
spiratory and expiratory neurons; the autorythmic centres and peripheral receptors, and their
inspiratory neurons stimulate the diaphragm and output fine tunes the breathing rhythm dur-
external intercostals for approximately 2 seconds ing activities such as speaking, sleeping, or
to cause inspirations and then the antagonistic ex- exercising.
piratory neurons fire for approximately 3 seconds (c) Proprioceptive stretch receptors in the
to permit passive or stimulate active expirations; lungs, pleura, and thoracic wall convey
thereby inspiratory and expiratory neurons coop- information about the degree of the filling of
erate in a negative feedback control relationship, the lungs and overfilling will cause a reflex
setting the basic rhythm of respiration (spontane- decrease in the strength of inspirations
ous ventilation, resting or tidal breathing); the dor-
ο Chemical influences: Changing levels of
sal respiratory group (DRG) neurons are involved
oxygen, carbon dioxide, hydrogen ion and
in altering the pattern for ventilation in response
bicarbonate ion in the blood are detected
to the physiological needs of the body for O2 and
and this visceral sensory information is
CO2 exchange and for blood acid-base balance;
routed to the hypothalamus and medulla
these neurons stimulate neurons in the ventral
where it stimulates or inhibits the action of
respiratory group (VRG) to achieve those effects;
components of the respiratory centre of the
they are responsive to sensory information from
brain
chemoreceptors and mechanoreceptors.

Figure1
Effect of Anesthesia on Respiratory Physiology is produced by the action on respiratory centre

rather than a slight effect on peripheral chemore-
Control of Breathing: Anaesthetic agents influence
ceptors.
rate, rhythm and intensity of discharge from respira-
tory centres. • Intravenous Agents: They produce brief stimula-
tion on induction which increases tidal volume,
Effect on respiratory drive: Most anaesthetic
inspiratory flow and frequency. This is abruptly
agents:
followed by a fall in ventilatory drive, accompa-
• Increase respiratory frequency by shortening in- nied by fall in tidal volume, inspiratory flow and
spiratory and to a larger extent expiratory time. sometimes a period of apnoea. Propofol abolishes
the response to hypoxaemia and is a potent
• Tidal volume is depressed, as is ventilator re-
depressor of chemoreceptor activity and upper
sponse to PaCO2.
airway reflexes. Ketamine is less depressant and
• There is active contraction of abdominal muscles produces greater inspiratory flows and marked
during expiration and there may be paradoxical expiratory braking. Opioids prolong the expiratory
inward movement of the ribcage in early inspira- pause and produce slowing of respiratory rate and
tion. obtund the response to rising PaCO2. They sup-
• Volatile Agents: Response to hypoxaemia dimin- press REM sleep and therefore, increase rebound
ished by low conc. of volatile agents. This effect REM that occurs when they are discontinued.

Benzodiazepines decrease chemosensitivity in Ketamine maintains airway patency by promoting

premedicant dose. Airway obstruction is a major muscle activity. Reflex responses occur in the upper
risk, especially in elderly. Adrenergic agonists airway where laryngospasm and apnoea responses
produce sedation and have shown to increase the to stimulation are common and a deep anesthesia is
response to elevations in PaCO2 so reducing the required if coughing, laryngospasm or bronchospasm
gradient of the ventilation response CO2 curve, occur on stimulation. Propofol in particular is effective
but not the resting response. in overcoming upper airway reflexes.
Effect of Chemoreceptors Effect of anesthesia on respiratory muscles
Peripheral and central chemoreceptors provide General anesthesia can affect the tone or strength
inputs to the respiratory centres. Sleep affects the of the respiratory muscles which is evident by the fall
changes which would normally be produced by the in FRC during the first 15 – 20 sec. after induction of
action of the chemoreceptors on the medulla, allowing anesthesia. FRC is reduced during anesthesia em-
PaCO2 to rise by 1-2 mm Hg in non-REM sleep and ploying a spontaneous breathing technique or positive
increasing the apnoeic threshold. REM sleep results pressure ventilation with paralysis.
in increased airway resistance and decreased upper
airway tone, potentially increasing the risk of upper
airway obstruction.
• Ventilation – PaO2 response curve: Ventilation
begins to increase at a PaO2 of 50 – 60 mm Hg
at rapidly at 32 mm Hg. Sudden acute hypoxia
stimulates ventilation within a few seconds.
• Ventilation – PaCO2 response curve: The re-
sponse is slower than that of hypoxaemia but
is linear up to high values of PaCO2. Ventilation
gets depressed when PaCO2 is between 97 and
195 mm Hg. The response curves have the same
gradient but are displaced to the left in acidosis.
Figure 2
Opioids and inhalational agents displace the curve
to the right and flatten the gradient. The gradient Postural effect on FRC is seen even in awake
of the response curve for a given pH is steeper subjects. Moving from upright to supine position
in hypoxaemia. decreases FRC by 700 ml. Anaesthesia decreases
FRC by another 300 – 500 ml. There is a fall in rib
Effect of anesthesia on the upper airway
cage volume of around 300 ml after induction of an-
The muscles of the upper airway keep it patent. aesthesia with propofol, but no change in abdominal
The dilator muscles maintain patency and constrictors compartment volume suggesting that the position and
are involved in swallowing. In a conscious patient airway shape of diaphragm is less affected than those of the
remains patent even at -60 cm H2O intrathoracic pres- rib cage. In the paralyzed ventilated patient and dur-
sures. During sleep this falls to -13 cm H2O. Anesthesia ing anaesthesia with spontaneous breathing, there is
lowers the tone of upper airway muscles and further a significant cephalad displacement of the dome of
promotes airway occlusion. Topical anesthesia of the diaphragm. Therefore, changes in lung volume are
upper airway increases airway resistance and makes likely to be due to a fall in chest wall tone with or with-
collapse more likely. Benzodiazepines, barbiturates, out fall in diaphragmatic tone (Figure 2). Fall in FRC
halothane reduce the activity of the nerves supplying can result in atelectasis which occurs by 3 methods: (i)
the upper airway more than they affect the diaphragm. Absorption of gases blocked behind blocked airways;

(ii) compression; and (iii) loss of surfactant. A decrease (dead space). During anaesthesia these two extremes
in lung volume will reduce traction on air passages and are more prevalent than in awake subjects. This is
lead to narrowing of bronchi and bronchioles leading confirmed by the finding of an increased spread of V/Q
to increased airway resistance, airway collapse and ratios during anaesthesia.
atelectasis. This results in reduced compliance and
Hypoxic pulmonary vasoconstriction (HPV): HPV
increased work of breathing. Compression atelectasis
normally reduces blood flow in areas of atelectasis, to
would occur particularly in lung bases if there was a
promote matching of ventilation and perfusion. Vola-
reduction in diaphragmatic tone allowing the pressure
tile agents impair HPV as alveolar anaesthetic conc.
in the posterior upper abdomen to be transmitted to
rises. For example, HPV is reduced by 50% by 1 MAC
the lower posterior lung units.
halothane and 20% by isoflurane.
Closing volume (CV): It is lung volume at which small
Effect of Regional Anaesthesia
airways collapse. CV > FRC in neonates and the over
40 years olds. Anaesthesia reduces FRC close to or The effects depend on the extent of the blockade.
below the CV in those in the middle age range. The Blocks that affect all lumbar and thoracic segments
effect is increased at extreme of age, obesity and even decrease inspiratory capacity by 20% and reduce
in those with abnormally high FRC, but poor lung elas- expiratory reserve to almost zero. Expiratory muscle
ticity and high resistance. This cause airway closure strength is greatly reduced during the action of lum-
and alveolar collapse. bar spinal anaesthesia, temporarily reducing cough
efficiency. V/Q mismatch is close to normal situation.
Ventilation Perfusion Mismatch
Overall mortality is reduced by 1/3rd in patients under-
Changes in lung volume and airway patency going local anaesthesia. This is due, at least in part,
cause a mismatch of lung ventilation and perfusion. to the significant reduction in respiratory complications
The V/Q ratio may be very low or zero in areas that including pulmonary emboli, respiratory depression and
are perfused but not ventilated, or extremely high in pneumonia after surgery.
those areas where there is ventilation but no perfusion

Vaporizers 23 Aruna Parameswari
01 VAPORIZERS
Professor Aruna Parameswari

Srmc, Chennai.
OUTLINE Vapor and gases

Introduction Every substance has its unique critical tempera-
ture above which it exists only as a gas, irrespective
Physics and laws of vaporization
of how much pressure is applied to it. At or below this
Factors affecting vaporization of a liquid critical temperature, it can exist in both its liquid and
Classification of vaporizers gaseous forms; the latter is called a vapor. Thus, a
vapor is the gaseous phase of a substance which is
Hazards of vaporizers
a liquid at room temperature and atmospheric pres-
Safety features in vaporizers sure.
Specific vaporizers Vapor pressure
Conclusion When a volatile liquid is kept inside a container

closed to atmosphere, molecules of liquid break away
Introduction
from the surface (due to their kinetic energy) and
Volatile inhalational agents have been in use enter the space above, forming a vapor. The vapor
from the dawn of anesthesia; from the Schimmelbusch exerts a pressure on its surroundings, which is known
masks to modern electronically controlled vaporizers. as vapor pressure. Some of the molecules that have
Vaporizers are an integral part of modern-day anes- escaped while moving freely in the gaseous state will
thesia, allowing the delivery of safe concentrations of collide with the surface of the liquid and re-enter it.
volatile anesthetic agent. Eventually, there will occur an equilibrium in which the
Most of the inhalational anesthetic agents in use number of molecules re-entering the liquid equals the
today are liquids under normal conditions and must be number leaving it. At this stage, the vapor pressure is
converted into vapors before they can be used. at a maximum for the temperature of the liquid and so
is called the saturated vapor pressure (SVP).
A vaporizer is an instrument designed to:
a) facilitate the conversion of a liquid anesthetic into
its vapor form and
b) add a controlled amount of this vapor to the fresh
gas flow.
The purpose of the vaporizer is thus to deliver
reliably an accurate, adjustable concentration of an-
esthetic vapor.
Physics
For safe administration of inhalational agents us-
ing vaporizers, it is essential to understand the physics
behind vaporization: vapors and gases, saturated vapor
pressure, boiling point, heat of vaporization, specific
Fig.1. SVP increases non-linearly with
heat and thermal conductivity. temperature

If heat is supplied to the container, the equilibrium anesthetic. SVP is a measure of the volatility of the
will be shifted so that more molecules enter the vapor liquid anesthetic in the carrier gas: after equilibration
phase and the vapor pressure will rise. If heat is taken between the carrier gas and the liquid anesthetic,
away from the system, more molecules will enter the the concentration of highly volatile anesthetics (e.g.
liquid state and the vapor pressure will be lowered. It is isoflurane) in the gas will be higher than that of poorly
meaningless, therefore, to talk about vapor pressure of volatile anesthetics (e.g. methoxyflurane).
a liquid without specifying the temperature. However,
Anesthetics with a high SVP will require a smaller
the relationship between SVP and temperature is non-
proportion of the total gas flowing through the vaporizer
linear (Fig.1). Vapor pressures of the commonly used
to pass through the vaporizing chamber to produce a
anesthetic agents at 20°C are shown in Table.1.
given concentration than will anesthetics with a low
The concentration of anesthetic vapor in a gas is given SVP.
by the equation:
It follows that it can be extremely dangerous to
Gas concentration = Vapor pressure / Ambient pres- deliver anesthetics from vaporizers for which they were
sure not designed.
For example, at 200C, the concentration of gas in a Boiling point
sevoflurane-vaporizing chamber (assuming it is satu-
At a certain temperature, the boiling point, liquid
rated) will be:
molecules can enter their vapor phase within the liquid,
Sevoflurane concentration = 160/760 = 21% creating bubbles of saturated vapor that rise to the
surface and break free. Below this temperature, any
In order to give clinically useful concentrations of
formation of a bubble would be instantly crushed by
the agent, we dilute this with fresh gas.
the greater atmospheric pressure. Thus, boiling point
Vapor pressure depends only on the liquid and the of a liquid is the temperature at which the saturated
temperature vapor pressure is equal to the atmospheric pressure.
The most important factor governing vaporizer The lower the atmospheric pressure, the lower the boil-
design is the saturated vapor pressure (SVP) of the ing point. The boiling points of some commonly used
anesthetic agents at sea level are shown in Table.1.
Agent Boiling point (°C, 760 mmHg) SVP (torr, 20°C)

Halothane 50.2 243
Enflurane 56.5 175
Isoflurane 48.5 238
Desflurane 23.5 664
Sevoflurane 58.5 160
Table.1 Boiling point and saturated vapor pressure of some common agents
CONCENTRATION OF GASES called the partial pressure of that gas. The total pres-
sure of the mixture is the sum of the partial pressures
Two methods are used commonly to express the
of the constituent gases.
concentration of a gas or vapor: partial pressure and
volumes percent. Volume percent
Partial pressure It is the number of units of volume of a gas in re-

lationship to a total of 100 units of volume for the total
A mixture of gases in a closed container will exert
gas mixture. Volumes percent expresses the relative
a pressure on the walls of the container. The part of
ratio of gas molecules in a mixture, whereas partial
the pressure exerted by any one gas in the mixture is
pressure expresses an absolute value.

Partial pressure/total pressure = Volumes percent vaporization (the latter being exacerbated at
/ 100 high gas flow rates). As temperature decreases,
the output of the vaporizer will decrease. These
Although gas and vapor concentrations are most
problems can be overcome by Temperature sta-
commonly expressed in volumes percent, patient up-
bilization and temperature compensation.
take and the level of anesthesia are directly related
to partial pressure but only indirectly to volumes per- Temperature stabilization: Construction of the vapor-
cent. izer using materials with high specific heat capacity
and thermal conductivity provides a heat sink, allowing
Heat of vaporization
heat to move rapidly between the vaporizing chamber
Latent heat of vaporization is the number of and the atmosphere. Plenum vaporizers are made of
calories needed to convert 1 g of liquid to vapor, without dense metals, while the Oxford Miniature vaporizer (a
temperature change in the remaining liquid. Thus, the draw-over vaporizer) uses glycol as a heat sink.
temperature of the remaining liquid will drop as vapor-
Temperature compensation: This is dealt with sepa-
ization proceeds, lowering vapor pressure, unless this
rately under vaporizer classification
is prevented.
• Time
Specific heat is the number of calories needed
to increase the temperature of 1 g of a substance by Vaporization causes the liquid anesthetic to cool
1 degree C. Manufacturers select materials for vapor- since heat is lost because of the latent heat of
izer construction with high specific heats to minimize vaporization of the anesthetic. Therefore, the
temperature changes associated with vaporization. output concentration will tend to fall over time.
Thermal conductivity - a measure of how fast a • Gas flow rate

substance transmits heat. High thermal conductivity is
Changes in carrier gas flow rate may affect vapor-
desirable in vaporizer construction.
izer output by:
Factors affecting vaporizer output
− Altering the proportion of the total gas flow
• Flow through the vaporizing chamber that passes through the vaporizing cham-
Varying the proportion of gas passing through the ber.
vaporizing chamber and bypass is the method by
− Altering the efficiency of vaporization. For
which vaporizer output is controlled.
example, at high flow rates, the gas leaving
• Efficiency of vaporization/ surface area of the the vaporizing chamber will tend to be less
liquid gas interface saturated (since the gas spends less time in
the chamber), so the output of the vaporizer
The greater the surface area of the liquid anes-
will tend to fall.
thetic agent exposed to the fresh gas, more is the
vaporization of the liquid agent. Vaporizers may • Carrier gas composition
incorporate a system of wicks and channels in
The composition of the carrier gas may affect
the vaporizing chamber to improve efficiency of
vaporizer output by:
vaporization and increase the output concentra-
tion of anesthetic − Changes in the viscosity and density of the
gas mixture affecting the proportion of the
• Temperature
total flow that passes through the vaporizing
The SVP of an agent decreases with decreasing chamber. The viscosities of air and nitrous
temperature. Changes in agent temperature can oxide are lower than those of oxygen. In
occur for two reasons – fluctuations in ambient the variable bypass vaporizers, the char-
temperature and the loss of the latent heat of acteristic of the flow splitting valve results

in decreased gas flow through the vapor- B). Based on the method of vaporization
izing chamber, and hence reduced output,
- Flow over
when using air and especially nitrous oxide
compared with 100% oxygen. This effect is - Bubble through
however, not clinically significant. - Injection
Ambient pressure C). Based on the method of temperature compensa-
Saturated vapor pressure is solely a function of tion
temperature. Therefore, if ambient pressure is reduced, - Mechanical thermo compensation
the (constant) SVP becomes a greater proportion of the
- Supplied heat
total (reduced) pressure, and the output concentration
(in volumes %) rises. The change in the agent concen- - Computerized thermo compensation
tration in the delivered gas flow can be calculated by:
D). Based on the location of the vaporizer
cal
P - Plenum
Agent %1 = Agent %cal x
1
P - low Resistance
Where agent %1 is the agent concentration at the E). Based on the agent specificity
present ambient pressure, P1 is the present ambient - Agent specific
pressure, Pcal is the atmospheric pressure at which
- Multiple agent
vaporizer was calibrated and agent %cal is the agent
% delivered at the calibrated atmospheric pressure. Method of regulating output concentration
But the partial pressure of the agent will not The vapor pressures of most anesthetic agents
change with change in ambient pressure and since it at room temperature are much greater than the partial
is the partial pressure that determines level of anes- pressure required to produce anesthesia. To produce
thesia, the clinical effect of change in ambient pressure clinically useful concentrations, a vaporizer dilutes
is insignificant and the vaporizer can be used in the saturated vapor in one of several ways. Depending on
same way at high altitude, sea level or under hyperbaric this, vaporizers can be classified as :
conditions.
A) Variable bypass vaporizer
This, however, does not apply to the desflurane
The gas that flows through the vaporizer is split
Tec 6 vaporizer. The Tec 6 vaporizer is pressurized to
so that some of the gas flows through the vaporiz-
2 atm; there is no compensation for ambient pressure
ing chamber (the part of the vaporizer that contains
and thus the concentration delivered in the fresh gas
the liquid anesthetic agent) and the remainder goes
flow is stable, regardless of ambient pressure. Thus,
through a bypass (without passing through the vapor-
the dial setting must be increased to maintain partial
izing chamber) to the Vaporizer outlet. Both gas flows
pressure of the agent at high altitudes.
(flow through the vaporizing chamber and the bypass)
Classification of vaporizers join downstream of the vaporizing chamber where gas
exits the vaporizer at the desired concentration.
Vaporizers are classified based on various methods.
Some of the most commonly used methods are: The ratio of the bypass gas to the vaporizing
chamber is called the splitting ratio.
A). Based on regulating the output concentration
Splitting ratio = Gas going through the bypass/
- Variable bypass
Gas going through the vaporizing chamber
- Measured flow
The splitting ratio depends on the ratio of re-
- Electronic vaporizers sistance in the two pathways. The resistance in turn

depends on the size of the variable (adjustable) orifice The splitting ratio may also depend on the total
which is present at the inlet of old vaporizers and at the flow to the vaporizer.
outlet of modern vaporizers.
Conc./Agent Halothane Enflurane Isoflurane Sevoflurane

1% 46:1 29:1 44:1 25:1
2% 22:1 14:1 21:1 12:1
3% 14:1 9:1 14:1 7:1
Table 2 : Gas flow splitting ratios for different agents
B) Measured flow vaporizers be done by using baffles or spiral tracks to lengthen

the gas pathways over the liquid. Another method is to
In these vaporizers, the vaporizer heats the an-
employ wicks that have their bases in the liquid anes-
esthetic agent to a temperature above its boiling point
thetic agent. The liquid moves up the wick by capillary
(so it behaves as a gas) and this is then metered into
action. (Fig. 2 a and b)
the fresh gas flow. A measured flow is sent by a sepa-
rate oxygen flow meter to pass to the vaporizer with
the output being at saturated vapor pressure for the
anesthetic agent. In order to dilute this otherwise lethal
concentration, output from that flow meter is combined
with gas passing from the main flow meter.
Some of the older Measured-flow vaporizers
include Copper kettle, Verni-trol and Metomatic vapor-
izers.
The modern example of a measured flow vapor-
izer is the desflurane Tec 6 vaporizer.
C) Electronic vaporizers
In these vaporizers, a computer calculates the car-
rier gas flow that needs to pass through the vaporizing
chamber in order to produce the desired anesthetic
gas/vapor concentration.
Another type of electronic vaporizers withdraws
a calculated amount of liquid agent from the agent Fig. 2a: Flow over Vaporizer
bottle and injects that liquid into the breathing system Fig. 2b: Flow over Vaporizer with wicks and
or fresh gas flow. The amount of liquid that is injected baffles
is adjusted to achieve the desired anesthetic concen-
2. Bubble through
tration.
The carrier gas is bubbled through the liquid an-
Vaporization methods
esthetic agent. A known amount of the liquid anesthetic
1. Flow over agent is then injected into the fresh gas flow. (Fig.3)
A stream of carrier gas passes over the surface
of the liquid i.e. it “FLOWS OVER” the surface of the
liquid. Increasing the area of the gas liquid interface
enhances the efficiency of the vaporization. This can

the vaporizing chamber. The rod is attached only at

the base of the brass jacket, which has a higher coef-
ficient of expansion. The outer surface of the jacket is
immersed in liquid anesthetic agent in the vaporizing
chamber. As the aforementioned liquid cools, the brass
jacket contracts more than the Invar, which is pushed
upwards into the bypass, restricting the flow of gas.
(Fig. 4c and d)
Fig. 3 : Bubble through vaporizer
3. Temperature compensation
Energy in the form of heat is lost as liquid is va-
porized and the liquid temperature falls. This results
in fall in saturated vapor pressure which decreases
the vaporizer output. Methods have been employed
to maintain constant vapor output with fluctuation in
liquid anesthetic temperature.
a) Mechanical compensation
This is done by altering the splitting ratio as tem-
perature changes so that the percentage of carrier
gas that is directed through the vaporizing chamber is
increased or decreased. With fall in temperature, the
thermal element restricts the bypass flow causing more
carrier gas to pass through the vaporizing chamber and
the opposite occurs as the temperature increases.
(c)
Two types of mechanical compensation are normally
used: Fig. 4 : Two different types of mechanical ther-
mocompensation
The first consists of two dissimilar metals or alloys
b) Supplied heat
placed back to back (i.e a bimetallic strip). As the two
metals have different rates of expansion and contrac- An electric heater can be used to supply heat
tion with temperature, the device has the ability to to a vaporizer and maintain it at a desired constant
‘bend’. It can therefore be used to vary the degree of temperature.
occlusion in the aperture of the gas channel (usually c) Computerized thermocompensation
the bypass) and thus alter the flow of carrier gases
Temperature compensation is achieved by com-
through it. (Fig.4a and b)
puter control.
In the second arrangement, the bimetallic device
4. Based on resistance
consists of a central rod made of Invar, a metal alloy
with a low coefficient of expansion, sitting inside a brass Plenum Vaporizers have high resistance and
jacket, the top part of which is attached to the roof of therefore require a pressurized source to provide a flow

of gas. They are usually placed outside the breathing maximal with large pressure swings, low flows and a
circuit (VOC or “vaporizer out of circuit” configuration), low dial setting. Modern vaporizers are relatively im-
on the back bar of the anesthetic machine, downstream mune (older vaporizers are certainly not immune) due
of the flow meters. Most of the modern vaporizers are to check valves between the vaporizer outlet and the
plenum vaporizers. common gas outlet, smaller vaporizing chambers, or
tortuous inlet chambers. Any of these design features
Draw-over vaporizers require a sub-atmospheric
prevent gas which has left the vaporizers from re-
pressure distal to the vaporizer, to ‘draw’ the fresh gas
entering it. (Fig.5)
flow through. This is typically the patient’s own respi-
ratory effort, so they require a low internal resistance.
This type of vaporizer is most useful when pressurized
gas sources are not available. They are not as ac-
curate as plenum vaporizers owing to such variable
flow rates, but can be used within the breathing circuit
(VIC or “vaporizer in circuit” configuration). Examples
include the ether vaporizer EMO and the OMV (Oxford
Miniature vaporizer).
Effect of altered barometric pressure
Most vaporizers are calibrated at sea level. Since Fig. 5 : Elongation of the inflow channel prevents
they can be used in hyperbaric chamber or at high alti- saturated vapor from reaching the bypass
tudes where atmospheric pressure is low, it is important
Pressurising effect
to know how they will perform when barometric pres-
sure is changed. The ASTM (American Society of Test- This is a decrease in concentration of the vapor-
ing and Materials) requires that the effect of changes in izer output when the overall pressure (that is, both in the
ambient pressure on Vaporizer performance be stated bypass and the vaporizing chamber) in the vaporizer is
in the accompanying documents. raised. The mechanism is that the partial pressure of
vapor generated is dependent solely on temperature,
Effect of rebreathing
and therefore at a high internal pressure, the vapor
Rebreathing causes a difference between vapor- forms less of the fractional composition of the number
izer setting and inspired concentration. With significant of molecules. Consequently, when the gas expands to
rebreathing, only an agent analyzer can provide an atmospheric pressure at the common gas outlet, the
accurate value of the inspired agent concentration. delivered concentration of the vapor will be less than
that intended. The effect is maximal with large vapor-
Effect of intermittent back pressure
izing chambers at high flows and high pressures.
Pumping effect
Hazards and safety features of contemporary va-
It is due to the effect of intermittent back pressure porizers
transmitted from the breathing circuit due to positive
Hazards
pressure ventilation or use of the oxygen flush valve. It
can increase vaporizer output. The surge in back pres- • Incorrect agent
sure forces gas in the back bar (which is not saturated
• Tipping
with vapor) back into the vaporizing chamber, and the
gas in the vaporizing chamber (which is saturated with • Simultaneous inhaled agent administration
vapor), retrogradely into the bypass channel. When the • Reliance on breath by breath gas analysis rather
pressure subsequently falls, the forward flow increases than preventive maintenance
the concentration of the delivered vapor. The effect is
• Overfilling

• Leaks The ASTM (American Society of Testing and

Materials) machine standard recommends that a va-
• Electronic failure
porizer designed for a single agent to be fitted with a
Safety features permanently attached agent specific device to prevent
Important safety features include: accidental filling with a wrong agent.
• Keyed fillers In addition to preventing a vaporizer from being

filled with a wrong agent, these systems may reduce
• Low filling port
the air pollution associated with filling or draining a
• Secured vaporizers (less ability to move them vaporizer.
about minimizes tipping)
Types (Fig.6)
• Interlocks
Funnel fill system
• Concentration dial increases output in all when
Keyed fill system
rotated counterclockwise (as seen from above)
Quick fill system
Filling systems
Easy fill system
There are a number of filling systems available.
Many are designed to allow a vaporizer to be refilled Desflurane specific filling system
only with a specific agent. Some systems are specific
to one vaporizer manufacturer only.
KEYED FILL SYSTEM SCREW FILL SYSTEM QUIK FIL SYSTEM
Fig 6: Different types of filling systems

Fig 8b. Select-a-tec mounting system.
Interlock devices
Interlock (vaporizer exclusion) systems prevent
Fig.7. Bottle adaptors that are colour coded more than one vaporizer from being turned ON at a
time.(Fig. 9 AND 10)
Vaporizer mounting systems
Permanent mounting
Permanent mounting means that tools are re-
quired to remove or install a vaporizer on the anes-
thesia machine. Advantages include less chances of
physical damage and leaks. Disadvantages include not
having enough mounting locations to accommodate all
vaporizers and difficulties in removing a malfunctioning
vaporizer.
Detachable mounting
These are standard on most of the modern an-
esthesia machines. They allow the Vaporizer to be
mounted and removed without the use of tools. Select Fig.9a. Select-a-tec in Datex Ohmeda
– a – tec system (Fig.8 a and b) and a similar system
from Drager Medical are widely used and Vaporizers
cannot be interchanged between these two systems.
Fig 8a. Select-a-tec mounting system. Fig.9b.Datex Ohmeda Interlock

to 390C, raising its SVP to 1460 mm Hg, that is nearly

2 atm. In addition to providing a stable SVP, this high
pressure removes the need for a pressurized carrier
gas- instead, the fresh or diluents gas is entirely sepa-
rate from the vaporizing chamber.
Fig.11. Schematic diagram of the TEC 6 vaporizer

Newer vaporizers
The GE Aladin cassette vaporizer
The vaporizer system used in the GE Anesthesia
Delivery Unit (ADU), is unique in that the single elec-
tronically controlled vaporizer is designed to deliver
five different inhaled anesthetics including halothane,
isoflurane, enflurane, sevoflurane, and desflurane. The
Vaporizer system consists of a permanent internal con-
trol unit housed within the ADU and an interchangeable
Aladin agent cassette which contains anesthetic liquid.
The Aladin cassettes are color keyed to their respective
Fig.10. North American Drager interlock system
anesthetic agent, and are also magnetically coded so
Tec 6 desflurane vaporizer that the Aladin system can identify which anesthetic
Desflurane has two physical properties, making cassette has been inserted. Though very different in
it unsuitable for use with a conventional vaporizer. external appearance, the functional anatomy of the
First, it has a very high SVP (664 mm Hg at 20⁰C). A Aladin cassette vaporizer (Fig. 12) is very similar to
conventional vaporizer would require high fresh gas that of the Dräger vapor 19.n, 20.n and the GE/Datex-
Ohmeda Tec 4, Tec 5, and Tec 7 vaporizers.
flows to dilute it to within clinically useful concentrations,
making it uneconomical.
Secondly, it has a low boiling point (23.5⁰C). At
room temperature, it will intermittently boil resulting in
large fluctuations in agent delivery. When boiling, there
will be excessive agent delivery; however, it will then
cool due to a large loss of latent heat of vaporization,
resulting in an exponential decrease in SVP and under
delivery of agent.
The Ohmeda Tec 6 overcomes these problems Fig. 12 : Aladdin cassette and a cutaway cassette
by using an electrical filament that heats the desflurane showing the lamellae

The Aladin system is functionally similar to these A fixed restrictor is located in the bypass chamber,
conventional Vaporizers because like them, it con- and it causes flow from the Vaporizer inlet to split into
sists of a bypass chamber and Vaporizing chamber. two flow streams (Fig. 14). One stream passes through
The heart of the Aladin system is the electronically the bypass chamber, and the other portion enters the
regulated flow control valve located in the Vaporizing inlet of the vaporizing chamber and passes through a
chamber outlet. This valve is controlled by a central one-way check valve. The presence of this check-valve
processing unit (CPU). The CPU receives input from is unique to the Aladin system. This one-way valve
multiple sources including the concentration control prevents retrograde flow of the anesthetic vapor back
dial, a pressure sensor located inside the Vaporizing into the bypass chamber. Its presence is crucial when
chamber, a temperature sensor located inside the delivering desflurane if the cassette temperature is at
Vaporizing chamber, a flow measurement unit located or above the boiling point for desflurane (22.8°C). A
in the bypass chamber, and a flow measurement unit precise amount of vapor-saturated carrier gas passes
located in the outlet of the Vaporizing chamber. The past the flow control valve, which is electronically regu-
CPU also receives input from the flow meters regard- lated by the CPU. This flow then rejoins the bypass flow
ing the composition of the carrier gas. Using data from and is directed to the outlet of the vaporizer. During
these multiple sources, the CPU is able to precisely operating conditions in which high fresh gas flow rates
regulate the flow control valve to attain the desired and/or high dial settings are used, large quantities of
Vapor concentration output. Appropriate electronic anesthetic liquid are rapidly vaporized. As a result of
control of the flow control valve is essential to the proper vaporative cooling, the temperature of the remaining
function of this Vaporizer. liquid anesthetic and the vaporizer cassette decrease.
To offset this cooling effect, the Aladin system is
equipped with a fan which forces warmed air from an
“agent heating resistor” across the cassette (the sump
for the vaporizer) to raise its temperature when neces-
sary. The fan is activated during two common clinical
scenarios: (1) when rapidly increasing the desflurane
concentration, and (2) during inductions using high
sevoflurane concentrations.
Drager DIVA Vaporizer
The Drager DIVA (Direct injection of vapor anes-
thetic) vaporizer (Fig.15.a) is a measured-flow type of
vaporizer requiring a separate air supply. Integrated
into the Zeus anesthetic machine, it can form part
of a closed anesthetic system. It utilizes closed-loop
feedback control to determine the amount of volatile
agent allowed through a closing valve into a heated
vaporization chamber; (Fig. 15.b.) this then passes
either directly into the breathing system or through a
mixing chamber into the fresh gas flow. The control unit
monitors the pressure of volatile agent in the vaporizing
Fig. 13 : Diagram of an Aladin cassette, 1 = lamel- chamber, the fresh gas flow, and the target-expired
lae, 2 = metal plate, 3 = inflow back valve, 4 =
volatile concentration, to ascertain the amount of
outflow back valve, 5 = temperature sensor, 6 =
handle, 7 = filling system, 8 = ball valve, 9 = air volatile agent required to be released to maintain the
channel, 10 = cassette ID magnets, 11 = liquid desired concentration at the patient end. Thus, quan-
level window titative closed-system anesthesia can be realized.

Fig.14. Working principle of the ADU
Conclusion
Knowledge of the principles of operation of va-
porizers is essential to the proper understanding of
their functions. Modern plenum vaporizers, if used as
intended by the manufacturers are (apart from recom-
mended service schedules) maintenance free devices
that provide accurate concentrations of vapor over the
range of conditions encountered in everyday clinical
practice. Future developments may occur in conjunc-
tion with the discovery of novel volatile anesthetic
agents and there is the possibility of closed systems,
Fig.15a. DIVA (Direct injection of vapor where vaporizer control may be linked directly to patient
anesthetic) vaporizer parameters via feedback mechanisms.
Recommended reading
1. Jerry A Dorsch, Susan E Dorsch. Understanding
anesthesia equipment. Fifth edition. Lippincott
Williams and Wilkins: 121 – 189.
2. Andrew J Davey, Ali Diba. Ward’s Anaesthetic
Equipment. Fifth edition. Elsevier Saunders: 65
Fig. 15.b. Schematic drawing of the DIVA
– 89.
metering system

3. Young J, Kapoor V. Principles of anaesthetic 6. Hendrickx et al. The ADU Vaporizing Unit: A New
Vaporizers. Anesth Int Care Med 2010;11:140- Vaporizer. Anesth Analg 2001;93:391-5.
143.
7. Baum JA. New and alternative delivery concepts
4. Boumphrey S, Marshall N. Understanding Vapor- and techniques. Best Pract Res Clin Anaesthesiol
izers. CEACCP 2011; 11(6):199-203. 2005;19(3):415-428.
5. Schober P, Loer SA. Closed system anaesthesia
– historical aspects and recent developments. Eur
J Anaesthesiol 2006; 23:914-920.

Autonomic Nervous System - What Anesthesiologist
needs to know? 36 Akilandeswari M
01 AUTONOMIC NERVOUS SYSTEM - WHAT ANESTHESIOLOGIST

NEEDS TO KNOW?
Associate Professor, Akilandeswari M

Srmc, Chennai.
The autonomic nervous system plays a crucial role thoracic (T1) and the third lumbar (L3) level . These
in maintaining the homeostasis of the internal mileu in fibers make synaptic connections in the 22 pairs of
response to the dynamic variations of the physiological ganglia termed the bilateral sympathetic chain. The
variables in day to day life. However this constancy preganglionic fiber has several potential destinations
can be disturbed after regional and general anesthesia once it enters a paravertebral ganglion. (FIG.1)
due to the alteration in autonomic tone and reflexes.
The use of intravenous and inhaled anesthetics may
cause hypotension directly through vascular smooth
muscle dilation and cardiac depression. The drugs
and therapeutic maneuvers used to restore physiologic
equilibrium directly target ANS effector sites. The co-
existing medical illness affecting autonomic nervous
system integrity can further lead to wide flucatuations in
hemodynamics ultimately influencing the perioperative
morbidity and mortality. So understanding the anatomy,
physiology and the pathophysiological changes caus-
ing autonomic alterations in the intraoperative period
is imperative to decide on the choice of drugs during
the intraoperative period so that there are minimal
perturbations from the baseline parameters.
The autonomic nervous system (ANS) is com- Figure 1 The pathways of sympathetic
posed of 2 anatomically and functionally distinct divi- preganglionic fibres.
sions, the sympathetic system and the parasympathetic
• it can synapse with one or more sympathetic
system. Both systems are tonically active providing
neurons in the ganglion
some degree of nervous input to a given tissue at all
times. Therefore, the frequency of discharge of neurons • ascend or descend in the paravertebral chain
in both systems can either increase or decrease, im- and synapse with neurons at other levels
proving its ability to more precisely regulate a tissue’s • synapse in the ganglion with a postganglionic
function. fiber that leaves the paravertebral chain
Sympathetic nervous system (SNS) • join a somatic nerve and travel to an effector
The primary relay or integration region is the site (e.g. blood vessels)
medullary vasomotor center, which integrates neural • synapse with an intermediate ganglion cell or
information fromthe central autonomic network (CAN) with a prevertebral ganglion cell.
and peripheral sensors.The CAN consists of four pri-
mary areas: the cerebral cortex, amygdala, hypothala- The ratio of preganglionic fibers to postganglionic
mus, and medulla and receives input from peripheral fibers is about 1:20 and this divergence of the pregan-
visceral and somatic receptors. The SNS consists of glionic neuron results in coordinated sympathetic
preganglionic fibers that arise from the intermediolat- stimulation to tissues throughout the body. The end
eral column and exit the spinal cord between the first organs innervated by the SNS include eyes, secretory

organs (including the sweat glands), heart, blood ves- sacral region of the spinal cord exit the CNS and join
sels, adrenal medulla, abdominal and pelvic viscera, together to form the pelvic nerves. These nerves inner-
and piloerector muscles. vate the viscera of the pelvic cavity (eg, lower half of the
large intestine and organs of the renal and reproductive
Parasympathetic system
systems). Because the terminal ganglia are located
The preganglionic neurons of the parasympathetic within the innervated tissue, there is typically little
system arise from several nuclei of the brainstem and divergence in the parasympathetic system compared
from the sacral region of the spinal cord (segments S2- to the sympathetic system. In many organs, there is a
S4). The axons of the preganglionic neurons are quite 1:1 ratio of preganglionic fibers to postganglionic fibers.
long compared to those of the sympathetic system and Therefore, the effects of the parasympathetic system
synapse with postganglionic neurons within terminal tend to be more discrete and localized, compared to the
ganglia which are close to or embedded within the sympathetic system where a more diffuse discharge is
effector tissues.The preganglionic neurons that arise possible.
from the brainstem exit the CNS through the cranial
Neurotransmitters of the autonomic nervous
nerves. (Fig.2) The occulomotor nerve (III) innervates
system
the eyes, the facial nerve (VII) innervates the lacrimal
gland, the salivary glands and the mucus membranes The two most common neurotransmitters re-
of the nasal cavity; the glossopharyngeal nerve (IX) leased by neurons of the ANS are acetylcholine and
innervates the parotid (salivary) gland; and the vagus norepinephrine. Neurotransmitters are synthesized in
nerve (X) innervates the viscera of the thorax and the the axon varicosities and stored in vesicles for subse-
abdomen (eg, heart, lungs, stomach, pancreas, small quent release. Nerve fibers that release acetylcholine
intestine, upper half of the large intestine, and liver). are referred to as cholinergic fibers. These include all
The physiological significance of this nerve is clearly preganglionic fibers of the ANS, both sympathetic and
illustrated by its widespread distribution and the fact parasympathetic systems; all postganglionic fibers of
that 75% of all parasympathetic fibers are in the vagus the parasympathetic system; and sympathetic post
nerve. The preganglionic neurons that arise from the ganglionicfibers innervating sweat glands. Nerve fibers
that release norepinephrine are referred to as adren-
ergic fibers. Most sympathetic postganglionic fibers
release norepinephrine. (Fig.3)
Figure 3. The neurotransmitters of autonomic

Figure 2. Organisation and distribution of the
nervous system
autonomic nervous system

The cells of the adrenal medulla are considered by any of these neurotransmitters is determined by
modified sympathetic postganglionic neurons. Instead the receptor distribution in a particular tissue and the
of a neurotransmitter, these cells release hormones biochemical properties of the cells in that tissue, spe-
into the blood. Approximately 20% of the hormonal cifically, the second messenger and enzyme systems
output of the adrenal medulla is norepinephrine and present within the cell.
the remaining 80% is epinephrine. The effect caused
Features Acetylcholine Norepinephrine Epinephrine
Site of release All post ganglionic Most sympathetic Adrenal medulla
neurons of postganglionic neurons; (80% of secretion)
parasympathetic adrenal medulla
system. (20% of secretion)
All preganglionic fibres
of autonomic system.
Postganglionic neurons
of sympathetic system
supplying sweat glands
Receptor Nicotinic , muscarinic ɲ1,ɲ 2, ɴ1 ɲ1,ɲ 2, ɴ1, ɴ2

Termination of Enzymatic degradation Reuptake into nerve Metabolic
Activity by cholinesterase terminals. transformation by
Diffusion out of synaptic catechol-O-methyl-
cleft. transferase
Metabolic within liver.
transformation by
monoamine oxidase.
Acetylcholine binds to 2 types of cholinergic present in the motor end plate and the N2 neuronal
receptors. Nicotinic receptors are found at autonomic receptors are found at the autonomic ganglia and in
ganglia, neuromuscular junction and in the central the CNS. The muscarinic receptors are of 5 types and
nervous system. They mediate excitatory responses they evoke excitatory response except M2 and M4 that
and are divided in two types. The N 1 receptors are mediate the inhibitory responses.
Cholinergic Pharmacology
Target Localization Effect Agonist Antagonist
Nicotinic (N)N Autonomic Fast depolarization succinylcholine Trimethaphan
ganglia, of postganglionic
CNS neuron
Nicotinic (N)M Neuromuscular Motor end-plate Succinylcholine Tubocurarine
junction (NMJ) depolarization, vecuronium
muscle contraction
Muscarinic (M1) CNS, autonomic Attention, memory, Oxotremorine, Scopolamine,
Ganglia arousal cevimeline, Pirenzepine
xanomeline
Muscarinic (M2) CNS, heart (SA Reduced HR, AV Carbachol, Scopolamine,
and nodal pilocarpine Atropine
AV node) Conduction iptratrophium
Muscarinic (M3) Smooth muscle, Smooth muscle Cevimeline, Atropine,
exocrine glands contraction, Pilocarpine iptratrophium
increased glandular
secretions
Muscarinic (M4) CNS Cognition Xanomelin Atropine,
pirenzepine
Muscarinic (M5) CNS Atropine

Anticholinergic drugs
Drug Sedation HR GI tone Airway Mydriasis Duration

secretion iv im
Atropine + ++ -- – + 15–30 min 2–4hrs
Scopalamine +++ –/+ - --- +++ 30–60 min 4–6 hrs
Glycopyrolate 0 ++ --- --- 0 2–4 h 6–8 h
Atropine and scopolamine are tertiary amines

and can easily cross the placenta and the blood–brain
barrier into the brain. Glycopyrrolate is a quaternary
amine and does not crossthe blood–brain barrier.
Their anticholinergic function is due primarily to the L
stereoisomer, although the drugs contain equal parts
of both L and the D isomers. Low doses of atropine
and scopolamine exert their effects within the CNS,
augmenting vagal outflow, which may result in bra-
dycardia. At the usual clinical doses atropine acts at
peripheral muscarinic receptors to block the action of
ACh, thereby increasing heart rate and pupil size while
reducing secretory gland activity, which results in both
Figure 4 Negative feed back mechanism of
an antisialogogue effect and anhydrosis.
alpha adrenoreceptor
Adrenergic receptors
β adrenoceptors.
There are 2 classes of adrenergic receptors al-
The β1 receptors are predominant in the heart
pha and beta. The alpha adrenoceptors exist at both
located primarily in the sinoatrial and atrioventricular
presynaptic andh postsynaptic neuro effector junction
node, myocardium, ventricular conduction system
sites throughout the human body and are involved in
with a few number of β2 receptors in the same. Both
cardiovascular regulation, metabolism, consciousness
subtypes of beta receptors on the heart are excitatory
and nociception.The alpha1 receptors are more widely
and stimulation leads to an increase in cardiac activity.
distributed on the effector tissues compared to alpha
The normal ratio of β1 and β2 recetors in the heart is
2 receptors and classified as alpha1A, alpha1B and
3:1.
alpha1D. They play a major role in regulating the arte-
riolar tone. The β2 adrenergic receptors are found on smooth
muscle of blood vessel, bronchi, uterus and bladder in
Alpha 2 receptor stimulation results in ‘‘pre-
several organ systems. These receptors tend to be in-
synaptic inhibition’’ causing decrease in the release
hibitory and cause relaxation of the smooth muscle.
of further norepinephrine from the post ganglionic
sympathetic neuron. (Fig.4)They cause contraction of The β3 receptors are present in the omentum,
vascular smooth muscle via postsynaptic receptors. brown fat and they mediate lipolysis, thermogenesis
Central effects include sedation, anxiolysis, analgesia, and the glucose uptake. Stimulation of β of receptor
and modulation of sympathetic and parasympathetic leads to an increase in intracellular cyclic AMP resulting
outflow from the CNS. The alpha 2 receptors are clas- in an excitatory or an inhibitory response depending
sified as alpha 2A, 2B and 2C. Both Alpha 1 and alpha on the type of cell.
2 receptors have equal affinity for norepinephrine. The α adrenoceptors respond to catecholamines
with an order of potency: norepinephrine ≥ epineph-

rine >> isoproterenol. Their order of potency on isoproteranol in failing heart by activating the β2 effects
β-adrenoceptors is isoproterenol > epinephrine ≥ of the drug. The number of beta receptors change sig-
norepinephrine. nificantly in relation to the amount of norepinephrine
levels and the response is as fast as 30 minutes follow-
In severe heart failure, the ratio of β1 and β2 is
ing the receptor blockade. So withdrawal of β blockers
altered to 3:2 due to down regulation of the β1 recep-
can lead to increase in receptor density resulting in
tors. The inotropic response is stimulated by the use
tachycardia.
Adrenergic receptor classification, location and their physiological effects
Type of receptor Location Response Dominance
ɲ1 Smooth muscle of blood Vasoconstriction Adrenergic
vessels
Bladder Contraction Adrenergic
Intestine Contraction Cholinergic
Liver and skeletal muscle Glycogenolysis Adrenergic
ɲ2 Platelets Aggregation Adrenergic
Sympathetic nerve endings Decrease Adrenergic
norepinephrine release
Blood vessel Vasoconstriction Adrenergic
Pancreatic ɴ cell ՝ insulin release Adrenergic
ɴ1 Heart ՛force , rate of Cholinergic
contraction and
excitability
Sympathetic nerve endings ՛NA release Adrenergic
Renal JG apparatus ՛renin release Adrenergic
Salivary gland Amylase release Cholinergic
ɴ2 Smooth muscle of Vasodilation Adrenergic
blood vessel, bronchi, uterus, Relaxation
bladder.
Heart force , rate of Cholinergic
contraction is
increased
Skeletal muscle hypokalemia Cholinergic
Pancreatic ɴ cell increase insulin Adrenergic
release
ɴ3 Fat Thermogenesis Adrenergic
Subcutaneous tissue lipolysis
Adrenergic pharmacology Epinephrine

The naturally occurring catecholamines include The actions of epinephrine at α and β receptors
norepinephrine, epinephrine and Dopamine. They act are dose dependent. At low doses (0.015 mcg/min/
on α and β receptors with dose-dependent actions of kg), β1 and β2 actions predominate producing includ-
dopamine on both dopaminergic and adrenergic recep- ing increased heart rate, cardiac output, contractility,
tors. and conduction and vasodilatation which turns pre-

dominantly to alpha effects at higher doses. The bolus Dopamine

dose for pressure support is 2-8mcgs intravenously,
Dopamine, an endogenous central neurotrans-
and 0.2mg/kg IV in cardiovascular collapse, asystole
mitter, is the immediate precursor to norepinephrine
and arrest rhythms. Selective β2 agonist effects of
in the catecholamine synthetic pathway. At low doses
epinephrine at 0.05 mcg/kg/min iv activates the so-
(0.5 to 3mcg/ kg/min), stimulation of dopaminergic D1
dium potassium pump in the skeletal muscle leading
postsynaptic receptors concentrated in the coronary,
to uptake of potassium in to the cell. It is very potent
renal, mesenteric, and cerebral beds and D2 presyn-
renal vasoconstrictor than nor epinephrine.
aptic receptors present in the vasculature and renal
Norepinephrine administration results in dose-depen- tissues promotes vasodilation and increased blood flow
dent hemodynamic effects on α- and β-adrenoceptors. to these tissues. At intermediate doses (3 to10 mcg/ kg/
At low doses, (0.05-08 mcg/kg/min) β1 actions predomi- min), dopamine weakly binds to β1- adrenergic recep-
nate and cardiac output and blood pressure increase. tors, promoting norepinephrine release and inhibiting
Larger doses of norepinephrine cause further increases reuptake in presynaptic sympathetic nerve terminals,
in blood pressure via arterial and venous smooth which results in increased cardiac contractility and
muscle contraction from α1-adrenoceptor stimulation. chronotropy, with a mild increase in SVR. At higher
It is used in the treatment of hypotension seconadary infusion rates (10 to 20 mcg/kg / min), α1-adrenergic
to neurogenic shock, sepsis. receptor mediated vasoconstriction dominates.
Table. The effect of catecholamines on the adreno receptors
Drug IV infusion ɲ1 ɴ1 ɴ2 DA
Dose
(mcg/min per kg)
Epinephrine
0.015 0 ++++ ++++
0.03–0.15 ++ ++++ ++++ 0
0.15–0.30 +++
Norepinephrine
0.1 +++++ +++ + 0
Dopamine
0.5–2 0 ++++
2-10 ++++ ++++ ++++
10
10-20 ++++ ++++
Isoproterenol
0.015mcg 0 ++++ ++++ 0
Dobutamine
5mcg + ++++ ++ 0
+ + + + - potent action, 0 - no effect, + - mild effect.

The synthetic catecholamines include isoprotere- It does not release nor epinephrine and acts by direct
nol, dobutamine and dopexamine. stimulation of β1 receptors and is the preferred drug in
chronic heart failure and low output state secondary to
Isoproterenol
infarction. There can be down regulation of receptors
It is the most potent activator at β1 and β2 receptors secondary to chronic administration of Dobutamine
with nil alpha effects. It increases the HR, myocardial infusion for more than 72hrs.
contractility, automaticity with decreased diastolic pres-
Noncatecholamine sympathomimetic amines
sures. The myocardial oxygen needs are increased and
there is no compensatory slowing of heart rate as the Ephedrine is commonly used non catecholamine
mean arterial pressures are not increased. sympathomimetic .The action of ephedrine is consid-
ered both direct activation of β1 receptors and indirectly
Dobutamine
it competes with norepinephrine for local reuptake, thus
Dobutamine is a cardio selective inotrope with resulting in elevated concentrations of norepinephrine
predominant β1 effects with minimal actions at the α at receptor sites. Ephedrine can reduce broncho-
and β2 effects. The drug has positive inotropic effect constriction by β2 agonism. In addition, ephedrine
with minimal increase in HR than with isoproterenol.

decreases renal and splanchnic blood flow, stimulates Autonomic reflexes

the CNS (e.g. increases MAC), and is associated with
Baroreceptor reflex
tachyphylaxis after extended use.
The baroreceptor reflexes continuously modulate
Amphetamines, amphetamine, mephenter-
the tonic activity of the ANS and operate as a rapid
mine, and metaraminol are synthetic vasopres-
control system to adjust cardiac output and peripheral
sors with predominately indirect actions on α- and
resistance to maintain arterial pressure around a ho-
β-adrenoceptors.
meostatic “set point.”
Alpha 1 receptor agonist
Arterial baroreceptors
Phenylephrine and methoxamine are selective
Mechanoreceptors located in the arch of the aorta
alpha 1 receptor agonist. It is used when vasoconstric-
and in the carotid sinus continually sense the prevailing
tion is needed and the cardiac output is adequate. The
blood pressure and send inhibitory information to the
duration of action is 5-10mins after bolus intravenous
vasomotor center. Efferent responses are directed to
injection of 40-100mcgs. This vasopressor can be use-
the heart, kidney, adrenal medulla, and the peripheral
ful in reversing ‘tet spells’ (right-to-left shunt) in patients
vasculature. Reflex changes in vascular resistance
with tetralogy of Fallot.
are mediated by efferent sympathetic nerve activity,
Alpha 2 receptor agonist whereas reflex heart rate responses are primarily me-
diated through the parasympathetic nervous system.
Agonists of alpha 2 -adrenoceptors include the
The carotid baroreceptor reflex is primarily involved
imidazolines (clonidine), phenylethylamines, and ox-
in controlling heart rate and the aortic baroreceptor
aloazepines. They decrease sympathetic outflow from
reflex preferentially regulates peripheral sympathetic
the CNS and reduce local norepinephrine release at
outflow.
nerve terminals. Other actions α2 agonists include va-
soconstriction via postsynaptic adrenoceptors, cardiac Low-pressure cardiopulmonary baroreceptor
antiarrhythmic effects, decreased cerebral blood flow, reflex
and inhibition of insulin and growth hormone secre-
Receptors in the atria and ventricles of the hu-
tion. Side effects of α2 agonists include bradycardia,
man heart (especially the veno-atrial junction) send
sedation, and dry mouth. Bradycardia occurs through
afferent signalsthrough the vagal nerves that mediate
a centrally mediated enhancement of vagal outflow.
a tonic restraint on sympathetic outflow. For example,
Dexmedetomidine, the (+)-stereoisomer of the when hemorrhage or orthostatic stress reduces cen-
imidazolidine compound medetomidine, is highly selec- tral venous pressure, these receptors are unloaded,
tive for α2-adrenoceptors. It is seven times more potent and sustained reflex increases in sympathetic outflow
for alpha 2 than alpha 1-adrenoceptors. Dexmedeto- are directed to the skeletal muscle and splanchnic
midine has strong analgesic, sedative, and anxiolytic vascular beds. The heart rate does not change, be-
actions. cause this low-pressure baroreflex is initiated before
any detectable decrease in systemic blood pressure
Sympatholytic drugs can block this sympathetic
occurs, suggesting that the arterial baroreceptors are
adrenergic system are three different levels.
not involved in the efferent response. This selective
Peripheral sympatholytic drugs such as alpha- peripheral sympathoexcitation from unloading of low-
adrenoceptor and beta-adrenoceptor antagonists block pressure baroreceptors provides the first line of defense
the influence of norepinephrine at the effector organ against hypotension when blood volume is reduced and
(heart or blood vessel). Ganglionic blockers interrupt therefore plays an important role in maintaining blood
impulse transmission at the sympathetic ganglia. Cen- pressure homeostasis.
trally acting sympatholytic drugs that block sympathetic
The chemosensitive receptors in the ventricle
activity within the brain.
send information to the central nervous system via

vagal pathways and elicit an inhibition of and periph- Intravenous induction agents
eral sympathetic nerve traffic and vagal stimulation.
1. Thiopentone depresses the vasomotor centre and
This reflex is classically termed the ‘Bezold-Jarisch
the sympathetic outflow resulting in pooling of
reflex’.
blood in the capacitance vessels. But the cardiac
Impact of anesthesia on the autonomic nervous output is minimally altered after thiopentone as the
system barareceptor reflexes are not suppressed which
results in compensatory tachycardia to counter
An intact baroreflex might lessen hemodynamic
the fall in blood pressure. The administration of
swings in the perioperative period. Surgical stimulation
centrally acting antihypertensives and beta an-
or blood volume loss leads to changes in blood pres-
tagonists can impair the barareceptor responses
sure that would be efficiently opposed or corrected by
and accentuate hypotension. Sympathetic reflex
baroreflex compensatory mechanisms. A reduction in
activation from stimulation of laryngeal and tra-
baroreflex “gain”or sensitivity would impair the compen-
cheal receptors is not fully suppressed by barbi-
satory response and result in greater hemodynamic
turates in clinically used dosages.
fluctuations. Vagally mediated bradycardia can result
from sretching the peritoneal cavity or other noxious 2. Propofol inhibits the sympathetic vasoconstric-
visceral stimuli, pressure on the contents of the orbit, tor activity in vascular smooth muscle causing
and volatile anesthetic mask induction in pediatric decrease in BP.The depression of baroreceptor
patients may cause increased vagal discharge and reflex activity and the sympathetic system results
severe bradycardia. in the predominance of vagal activity causing
bradycardia inspite of hypotension. It markedly
Inhalational agents
decreases SNS basal activity as well as the abil-
The inhalational agents produce dose dependent ity of the sympathetic nervous system to respond
suppression of the baroreceptor reflex. to hypotensive challenges. So vasopressors are
Halothane profoundly attenuates the barorecep- needed to correct fall in BP after propofol.
tor reflexes. Isoflurane preserves the baroreceptor 3. Ketamine causes direct stimulation of the CNS
reflex sensitivity up to 1% end tidal levels explaining eliciting increased sympathetic nervous system
the reason for tachycardia at even low minimal con- outflow for the cardiovascular stimulatory ef-
centration. Desflurane produces a massive surge in fects. It also increases the concentration of cat-
sympathetic activity and is not advisable as the sole echolamines in blood and it inhibits the uptake of
agent for anesthetic induction of patients with coronary norepinephrine in the post ganglionic neurons.
artery disease or any patient where increases in HR or The co administaration of inhalational agents
blood pressure are undesirable. depresses the sympathetic outflow from the CNS
Breathing nitrous oxide 60% does not inhibit reflex preventing the cardiovascular stimulating effects
sympathetic responses. Hence the enhanced sympa- of ketamine.
thetic function permitted by adding nitrous oxide to an 4. Benzodiazepines decrease baseline SNS activ-
anesthetic regimen may provide an improved hemody- ity and the ability to respond to arterial pressure
namic profile. Nitrous oxide, counteracts sympathetic changes. A combination of benzodiazepines with
nervous system (SNS) depression of volatile anesthet- opioids typically results in profound reduction of
ics when both drugs are administered simultaneously. SNS activity associated with decreases in sys-
This mechanism explains that similar anesthetic depths temic vascular resistance and arterial pressure.
can be achieved with less cardiovascular depression These cardiovascular changes are even more
by co-administration of nitrous oxide–volatile anesthetic pronounced when SNS activity is increased, e.g.
compared with administration of a volatile anesthetic during cardiac failure.
alone.

5. Etomidate preserves both sympathetic efferent to have CAN should be tested for cardiac stress before
activity and sympathetic reflex activation to hy- undertaking an exercise program.
potension and is the ideal drug for induction even Orthostatic hypotension is defined as a fall in BP
in patients with minimal cardiac reserve. of 30 mm Hg systolic or 10 mm Hg diastolic BP in re-
Autonomic neuropathy sponse to a postural change from supine to standing.
Symptoms include weakness, faintness, dizziness,
Autonomic failure occurs in approximately 1 in
visual impairment, and even syncope after a change
1,000 people and manifest with striking and paradoxic from a lying to a standing posture. Orthostatic hypoten-
responses to variety of physiologic and pharmacologic sion is due to damage to the efferent sympathetic
stimuli. Autonomic failure may be secondary to other vasomotor fibres.
diseases, such as diabetes mellitus, amyloidosis, or
Orthostatic tachycardia and bradycardia syn-
bronchogenic carcinoma, or be due to a primary auto-
dromes
nomic disorder such as multiple system atrophy (MSA)
such as Shy-Drager syndrome. Symptoms such as feeling faint or dizzy, circu-
moral paresthesia, and headache occur on change
Autonomic nervous system requires intact afferent
from a supine to an erect position. This may be due
and efferent limbs. Afferent neurons detect changes
to postural tachycardia syndrome (POTS), inappropri-
in blood pressure, temperature, and the myriad other
ate sinus tachycardia, neurocardiogenic syncope, or
vital processes controlled by the autonomic nervous
abnormalities in baroreceptor function. The hallmark
system, and communicate these changes centrally, and of these abnormalities is the absence of a fall in BP
efferent neurons engage effector systems to perturb or with standing, but a tachycardia or bradycardia with
restore homeostasis. Dysfunction of the afferent limb is the change in posture.
typically associated with labile hypertension, as seen in
baroreflex failure, particularly during the postoperative Silent myocardial ischemia
period after endarterectomy or other neck surgeries Autonomic neuropathy is the strongest predictor
affecting the carotid sinus nerve. of myocardial ischemia and they present with cough,
nausea and vomiting, dyspnea, tiredness, and ECG
Clinical manifestations of cardiac autonomic neu-
changes.
ropathy (CAN)
CAN may be associated with abnormalities in
Resting tachycardia and fixed heart rate are
LV systolic and particularly diastolic function in the
the late manifestations of neuropathy and reflect the
absence of cardiac disease in diabetic patients. Heart
parasympathetic failure in diabetic patients. Resting
failure is, common in patients in the presence of neu-
heart rates of 90 to 100 bpm and occasional heart rate ropathy, without evidence of coronary artery disease
increments up to 130 bpm occur. The highest resting or LV dysfunction.
heart rates have been found in patients with parasym-
pathetic damage, occurring earlier in the course of CAN Orthostatic and tilt-table testing
than sympathetic nerve function. In combined vagal Blood pressure and heart rate are measured twice
and sympathetic involvement, the rate returns toward in the supine position. The patient then is instructed to
normal but remains elevated. A fixed heart rate that is stand for 5 min. Blood pressure and heart rate are again
unresponsive to moderate exercise, stress, or sleep determined at 1, 3, and 5 min in the upright position.
indicates complete cardiac denervation. In autonomic failure, there may be little or no increase
in heart rate even though the blood pressure may de-
Exercise intolerance
crease more than 50 mmHg on the upright position.
Autonomic dysfunction impairs exercise toler-
Valsalva maneuver
ance, reduces response in heart rate and blood pres-
sure (BP), and blunts increases in cardiac output in The test is performed by blowing through a closed
response to exercise. Diabetic patients who are likely mouthpiece with a tiny leakage (16-gauge hole) to

maintain 40 mmHg for approximately 15 seconds. It breaths/min, the heart rate is monitored by EKG or
tests several components of the baroreflex arc. The ANSCORE device. A difference in heart rate of > 15
cardiovascular response has been subdivided into four beats/min is normal and < 10 beats/min is abnormal,
phases. R-R inspiration/R-R expiration > 1.17.
During phase I, there is a transient increase in Diastolic blood pressure response to isometric
BP secondary to the sudden increase in intrathoracic exercise
pressure being transmitted to the aorta.
The subject squeezes a handgrip dynamometer
In phase II, as continued strained expiration is to establish a maximum. Grip is then squeezed at 30%
maintained, venous return is reduced and cardiac maximum for 5 min. The normal response for diastolic
output decreases. This produces a decrease in blood blood pressure is a rise of > 16 mmHg in the other
pressure with reflex tachycardia. arm.
With the release of increased intrathoracic pres- The cold pressor test evaluates efferent sympathetic
sure, blood pressure abruptly decreases during phase function. It is carried out by placing the hand in a basin
III. filled with 50% ice and 50% water for approximately 1
During phase IV, there is a marked rise in blood min. The normal average response is an increment of
pressure that exceeds basal levels. This blood pressure 20 mmHg in systolic blood pressure. The blood pres-
overshoot is the result of both an increase in cardiac sure increase is blunted in patients with autonomic
output and peripheral vascular resistance. failure.
In patients with autonomic failure, the normal Deep breathing evaluates the vagal function on heart
tachycardia in phase II is blunted or absent and the rate modulation during slow inhalation for 5 s and ex-
phase IV blood pressure overshoot seen in normal halation for 5 s over 90 s. The sinus arrhythmia ratio
people also fails to occur. The ratio is derived from of the longest to the shortest interval is attenuated in
the maximal HR generated by the Valsalva maneuver those with autonomic failure.
divided by the lowest HR following the maneuver and
Hyperventilation tests the sympathetic response
should be > 1.2. The Valsalva maneuver increases
during deep and rapid (one breath per second) breath-
intrathoracic pressure as well as intraocular and
ing for 30 s to counteract the hypocapnea-induced
intracranial pressure. There is a risk of intraocular
systemic vasodilation. A significant decrease in blood
hemorrhage and lens dislocation during this
pressure indicates autonomic failure.
maneuver.
The thermoregulatory sweat test and the quantitative
Heart rate response to standing
sudomotor axon reflex test both determine the sweat
During continuous EKG monitoring, the R-R in- gland function and the integrity of efferent cholinergic
terval is measured at beats 15 and 30 after standing. sympathetic nervous system function. Sweating ab-
The initial HR responses to standing consist of a tachy- normalities are common in autonomic disorders; large
cardia at 3 and 12 seconds followed by a bradycardia areas of anhidrosis are found in patients with autonomic
at 20 seconds. The 30:15 ratio is normally > 1.03.The neuropathy due to various causes.
initial cardioacceleration is an exercise reflex, while the
subsequent tachycardia and bradycardia are baroreflex Perioperative management strategies for auto-
mediated. The 30:15 ratio (R-R interval at beat 30)/ nomic failure
(R-R interval at beat 15), has been recommended as The management must focus on ensuring hemo-
an index of cardiovagal function. dynamic stability perioperatively with adequate hydra-
Beat-to-beat heart rate variation tion, maintenance of euvolemia, and optimization of
pharmacologic treatment. Simple maneuvers such as
With the patient at rest and supine (no over-
raising or lowering the head of the bed have proven
night coffee or hypoglycemic episodes), breathing 6

to be helpful in ameliorating orthostatic symptoms for apnea could result in wide blood pressure variations
patients with autonomic failure. Hypotension during in patients with autonomic imbalance. The vocal cord
anesthesia is readily responsive to small doses of α1 dysfunction with coexisting gastroparesis predisposes
adrenoreceptor agonist, phenylephrine. them to the risk of aspiration upon induction of anes-
thesia.
Drug interactions in patients with autonomic fail-
ure Blood pressure control
The liver blood flow can decrease as much as The loss of cardiovascular reflexes in autonomic
30% with upright posture resulting in decreased hepatic failure predisposes patients to lifethreatening changes
clearance of drugs such as lidocaine. When patients in blood pressure in the intraoperative period. Acute
with orthostatic hypotension are receiving intravenous changes in blood volume (such as may be seen with
lidocaine, the plasma drug levels are almost twice as rapid saline infusion or with rapid blood loss) can result
high while seated versus supine, and this change in in a substantial increase or decrease in blood pres-
posture can occasionally result in a toxic seizure de- sure.
spite an unchanged infusion rate. A relatively fixed heart rate in response to car-
The response to various cardiovascular vasode- diovascular stimuli is characteristic in these patients.
pressor drugs also may be exaggerated, whereas the Bradycardia in patients with autonomic failure may not
response to other vasoactive agents is unpredictable. respond to atropine (because vagal tone is already
diminished in these patients), and alternatives such as
Tyramine infusion results in a slight increase in blood
isoproterenol or a temporary pacemaker is preferable
pressure in pure autonomic failure and normal pressor
in them.
response in MSA, whereas norepinephrine infusion
elicits an exaggerated pressor response in pure auto- Supine hypertension is present in more than half
nomic failure. of patients with autonomic failure and they present with
systolic blood pressure more than 200 mmHg. These
Ephedrine has lesser effect on blood pressure in-
increased pressures occur despite extremely low levels
crease due to mixed stimulation of adrenergic receptors
of both plasma norepinephrine and plasma renin activ-
and there is a concurrent increase in mean heart rate
ity. Even minor physical and pharmacologic perturba-
mediated by β1-receptors stimulation. As it enhances
tions in these patients may increase or decrease blood
release of norepinephrine from the postganglionic
pressure and/or cardiac output to dangerous levels.
neurons, it might only be effective in patients with
residual sympathetic activity and capacity to release This condition may complicate surgery when pa-
norepinephrine. tients are supine that is reversed by changing position
(reverse Trendelenburg) or judicious use of antihy-
Clonidine has a paradoxic action in cases of pertensive agents such as transdermal or intravenous
pure autonomic failure, instead of the typical central nitroglycerin without causing unwanted hypotension..
sympatholytic effect and blood pressure reduction. The Prone position during surgery as an alternative to the
stimulation of the postsynaptic α2-adrenergic and pos- traditional supine position is known to obstruct venous
sibly some α1 adrenergic receptors may predominate return and may result in hypotension.
over the presynaptic receptors on the norepinephrine-
The maintenance of baroreflex control of the cir-
depleted neurons. Therefore, doses above 0.2 mg
culation serves as a crucial counter regulatory mecha-
clonidine can occasionally increase blood pressure
nism in the face of surgical blood loss. Anesthetic
significantly.
agents can suppress the residual capacity to release
Airway management catecholamines and can induce diminished baroreflex
Apnea occurs in patients with autonomic dysfunc- gain, which further compromises pressor response
tion due to impaired central regulation of respiration during surgery. The response to pressor agents are
during anesthesia. The hypercapnea secondary to also unpredictable.

Ventilation autonomic tone. It assesses the variability of the time

intervals between cardiac contractions with reference
The inability of these patients to increase cardiac
to the mean values. A decrease in the HR variability
output through sympathetic activation makes them
is an independent predictor of morbidity and mortality
exquisitely sensitive to the effects of positive pressure
in critically ill patients and interventions to increase
ventilation on venous return and cardiac output. They
parasympathetic activity should be targeted. The use
are less tolerant of the pneuomoperitoneum associ-
of alpha 2 agonists in patients with CAD undergoing
ated with laparascopic procedures. Using smaller tidal
both cardiac and non cardiac surgery has resulted in
volumes and volume loading to control hypotension
an improved cardiac morbidity rate that might be at-
would be appropriate.
tributed to their effect of improving cardiovagal tone.
Hyperventilation and the resulting decrease in
blood carbon dioxide levels causes a rapid decrease in
blood pressure conversely, hypercapnea (such as can
be seen with hypoventilation or increased dead space
ventilation) can rapidly increase blood pressure 20
mmHg or more. Hence the blood pressure in patients
with autonomic failure can be partially be modulated
by manipulation of minute ventilation.
The inability to sweat in response to increase in
temperature and the absence of vasoconstriction in
response to hypothermia makes them vulnerable to
both intraoperative hyperthermia and hypothermia.
Constipation, due to decreased gastrointestinal HRV can be assessed either by calculation of
motility, and fecal incontinence are common in patients indices based on statistical analysis of R-R intervals
with autonomic failure resulting in inadequate bowel (time-domain analysis). Spectral analysis involves de-
preparation for colon surgery. Use of narcotics postop- composing the series of sequential R-R intervals into a
eratively may exacerbate the already sluggish intestinal sum of sinusoidal functions of different amplitudes and
motility and result in intestinal pseudoobstruction and frequencies. The power spectrum of HRV has been
toxic megacolon. shown to consist of 3 major peaks:
A thorough preoperative assessment, ideal choice (1) very-low frequency component (below 0.04 Hz),
of drug with individual titration of drug dosages and which is related to fluctuations in vasomotor tone
optimization of volume status along with the anesthetic associated with thermoregulation .
considerations mentioned above should be done in (2) Low-frequency (LF) component (around 0.1
patients with dysautonomia coming for surgery. Hz),which represents the so-called 10-s rhythm
Monitoring of ANS (Mayer waves) associated with the baroreceptor
reflex
Analysis of heart rate variability – A monitor to
evaluate autonomic tone (3) high frequency (HF) component (around 0.25 Hz),
which is related to respiratory activity.
The measurement of autonomic tone in the pe-
rioperative period helps in identifying the imbalance The very-low-frequency heart rate fluctuations are
prior to the end organ damage in high risk surgical pa- thought to be mediated primarily by the sympathetic
tients. The heart rate variability measurement offers a system, and the LF fluctuations are predominantly
diagnostic tool reflecting parasympathetic function and under sympathetic control with vagal modulation. The
variability in BP reflects the sympathetic component in HF fluctuations are under parasympathetic control.

Conclusion 2. David Glick. Autonomic nervous system. Basics of

anesthesia (sixth edition). Ronald D Miller, Manuel C
It is important to consider the functional status of
Pardo:66-75
the ANS and the autonomic sympathovagal balance
of our surgical patients and manipulate the autonomic 3. Norman Calvey, Norton Williams.Drugs and the
control effectively for better outcome in terms of peri- autonomic nervous system. Pharmacology for the
operative morbidity and mortality. The choice of drugs anesthetists;5 th edition:246-71
and the anesthetic technique should be based on an 4. Hossam I. Mustafa, Joshua P. Fessel, John Barwise.
individual risk benefit ratio so that there are no wide Dysautonomia Perioperative Implications.Anesthesi-
hemodynamic disturbances in the intraoperative period olgy 2012; 116:205–15
there by maintaining the autonomic balance in the
intraoperative period. In addition the anesthesiologist 5. Martin Neukirchen, Peter Kienbaum Sympathetic
should be aware of the issues surrounding autonomic Nervous System Evaluation and Importance for
neuropathy in orderto anticipate and possibly prevent Clinical General Anesthesia. Anesthesiology 2008;
perioperative complications. The future lies in develop- 109:1113–31
ing and use of intraoperative monitor which continously 6. Aaron I. Vinik, Dan Ziegler. Diabetic Cardiovascular
assesses the autonomic tone prior to the fluctuations in Autonomic Neuropathy. Circulation 2007, 115:387-
hemodynamics so that end organ damage is averted 397
earlier.
7. Alain Deschamps , André Denault. Analysis of heart
References rate variability: a useful tool to evaluate autonomic tone
1. Christofer D Barth, Thomas J Ebert. Autonomic nervous in the anesthetized patient. Can j anesth 2008 55:( 4):
system. Foundations of Anesthesia (Second Edition); 208–213
2006: Pages 403-17

Pharmacokinetics of Intravenous Drug Infusion 50 Naheed Azhar
01 PHARMACOKINETICS OF INTRAVENOUS DRUG INFUSION
Associate Professor Naheed Azhar

Vellore Medical College
Vellore
Pharmacokinetic models are mathematical de- Pharmacokinetic parameters

scriptions of how the body “disposes” of drugs. Phar-
Volume of distribution
macokinetics provides a mathematical basis to assess
the time course of drugs and their effects in the body. The volume of distribution (Vd) has no direct
It enables the following processes to be quantified: physiological meaning; it is not a ‘real’ volume and is
usually referred to as the apparent volume of distribu-
Absorption
tion. It is defined as that volume of plasma in which the
Distribution total amount of drug in the body would be required to
be dissolved in order to reflect the drug concentration
Redistribution
attained in plasma. If the drug has a large Vd that does
Metabolism not equate to a real volume, e.g. total plasma volume,
Excretion this suggests that the drug is highly distributed in tis-
sues. On the other hand, if the Vd is similar to the total
These pharmacokinetic processes, often referred
plasma volume this will suggest that the total amount of
to as ADRME, determine the drug concentration in the
drug is poorly distributed and is mainly in the plasma.
body when medicines are prescribed. A fundamental
The central volume of distribution (V1) describes
understanding of these parameters is required to de-
an apparent volume in a model that assumes that
sign an appropriate drug regimen for a patient. The
some tissues behave the same as plasma. Volume
effectiveness of a dosage regimen is determined by
of distribution at steady-state (Vdss) describes the
the concentration of the drug in the body. Ideally, the
apparent volume into which a drug will disperse during
concentration of drug should be measured at the site of
a prolonged infusion; it is the sum of all the compart-
action of the drug; that is, at the receptor. However, ow-
ment volumes in the model describing a drug’s kinetic
ing to inaccessibility, drug concentrations are normally
behaviour (V1, V2 and V3 in the three-compartment
measured in whole blood from which serum or plasma
model shown in). Movement of drug between different
is generated. It is assumed that drug concentrations in
compartments (distribution/redistribution) is determined
these fluids are in equilibrium with the drug concentra-
by the concentration gradient between compartments
tion at the receptor.
and the inter-compartmental clearance.
The measured drug concentrations in plasma or
Half-life
serum are a combination of bound and free drug that
are in equilibrium with each other. In routine clinical The time required to reduce the plasma concentra-
practice, serum drug level monitoring and optimisation tion to one half its initial value is defined as the half-life
of a dosage regimen require the application of clinical (t1/2).
pharmacokinetics. A variety of techniques is available
for representing the pharmacokinetics of a drug. The
most usual is to view the body as consisting of com-
partments between which drug moves and from which
elimination occurs. The transfer of drug between these
compartments is represented by rate constants where k is the “rate constant”.

This parameter is very useful for estimating how administered then all drugs will change from showing a
long it will take for levels to be reduced by half the first-order process to a zero-order process, for example
original concentration. It can be used to estimate for in an overdose situation.
how long a drug should be stopped if a patient has
Clearance
toxic drug levels, assuming the drug shows linear one-
compartment pharmacokinetics. Drug clearance (CL) is defined as the volume of
plasma in the vascular compartment cleared of drug
The rate of a reaction or process is defined as the
per unit time by the processes of metabolism and ex-
velocity at which it proceeds and can be described as
cretion. Clearance for a drug is constant if the drug is
either zero-order or first-order kinetics.
eliminated by first-order kinetics. Drug can be cleared
Zero-order reaction by renal excretion or by metabolism or both. Clearance
is the product of the first-order elimination rate constant
If the amount of the drug, is decreasing at a
(k) and the apparent volume of distribution (Vd).
constant rate, then the rate of elimination can be de-
scribed as the zero-order rate constant. The reaction CL total = k Vd
proceeds at a constant rate and is independent of the
Elimination rate constant
concentration of the drug present in the body. Drugs
that show this type of elimination will show accumula- Elimination is a non-specific term describing
tion of plasma levels of the drug and hence nonlinear any process that removes drug from plasma. There
pharmacokinetics. are several processes contributing to elimination:
distribution describes elimination attributable to a
drug temporarily being taken up by tissue other than
plasma; redistribution is the release of such temporary
stores back to plasma; and excretion the processes
that permanently removes a drug from the plasma.
Excretion is therefore a combination of metabolism
(producing metabolites) and excretion of unchanged
drug (e.g. from the kidneys or lungs). Metabolism to
active products may prolong duration of action, thus
altering the relationship between plasma concentration
of a drug and pharmacodynamic activity.
Clearance attributable to excretion describes
removal of drug from the body. Rate of elimination
First-order reaction
from one compartment to another is the product of
If the amount of drug is decreasing at a rate that concentration in the compartment from which drug is
is proportional to the amount of drug remaining in the being eliminated, and inter-compartmental clearance.
body, then the rate of elimination of the drug can be Rate of excretion is the product of central compartment
described as first-order rate constant.The reaction concentration and clearance. The relative importance
proceeds at a rate that is dependent on the concen- of distribution and excretion in removing a drug from,
tration of the drug present in the body. Most drugs and redistribution returning a drug to, plasma is central
used in clinical practice at therapeutic dosages will to our understanding of how plasma concentration
show first-order rate processes. In drugs that show a changes during and after infusion. These changes will
first-order elimination process as the amount of drug then be reflected in the effect compartment, but with a
administered increases, the body is able to eliminate time-lag. Modelling is a mathematical tool used to pre-
the drug accordingly and accumulation will not occur. dict the way in which plasma concentration varies over
However, if you continue to increase the amount of drug time. Each drug requires its own model as it is fitted

to observed drug behaviour. The three-compartment amount of drug eliminated in that same period. At
model for propofol will not be the same as that for steady state the plasma concentrations of the drug
fentanyl or remifentanil. If a drug has a CL of 2L/h, (Cssp ) at any time during any dosing interval, as well
this tells you that 2 litres of the Vd is cleared of drug as the peak and trough, are similar. The time to reach
per hour. If the Cp is 10 mg/L, then 20 mg of drug is steady-state concentrations is dependent on the half-
cleared per hour life of the drug under consideration
Hysteresis Intravenous infusion
The plasma concentration after an intravenous Some drugs are administered as an intravenous
bolus peaks nearly instantaneously in the plasma infusion rather than as an intravenous bolus
concentration but additional time is required for the
drug concentration in the brain to rise sufficiently to
induce unconsciousness. This delay between peak
plasma concentration and peak concentration at the
effect site is called hysteresis. Hysteresis is the clinical
manifestation of the fact that plasma is not the site of
anesthetic action, only the mechanism of transport.
Multiple doses
Some drugs may be used clinically on a single-
dose basis, although most drugs are administered
continually over a period of time. When a drug is
administered at a regular dosing interval (orally or IV),
the drug accumulates in the body and the serum con-
centration will rise until steady-state conditions have
Following a continuous infusion, the plasma
been reached, assuming the drug is administered again
concentrations will increase with time until the rate of
before all of the previous dose has been eliminated
elimination (rate out) equals the rate of infusion (rate in)
and will then remain constant. The plateau concentra-
tion, i.e. Cssp, is the steady-state concentration. Steady
state will be achieved in 4–5 times the t 1/2. That is 4 to
5 half lives or 3 time constants. When a constant infu-
sion is stopped, the drug concentrations in the plasma
decline in an exponential manner
Loading dose
The time required to obtain steady-state plasma
levels by IV infusion will be long if a drug has a long
half-life. It is, therefore, useful in such cases to admin-
ister an intravenous loading dose to attain the desired
drug concentration immediately and then attempt to
Steady state maintain this concentration by a continuous infusion.
Steady state occurs when the amount of drug To estimate the loading dose (LD), where Cssp
administered (in a given time period) is equal to the is the final desired concentration,

Accurate intravenous drug delivery requires ad-

justing the dose for accumulation of drug in peripheral
tissues
Pharmacokinetic models
These are hypothetical structures that are used
to describe the fate of a drug in a biological system
following its administration.
One-compartment model
is zero. As the infusion continues, C increases, initially

quickly, but then more slowly, as the rate of excretion
is initially slow but increases with increasing plasma
concentration. Thus, plasma concentration increases in
a negative exponential fashion. Equilibrium is reached
when input = output. The input rate is f mg min−1 and
output is the rate of excretion, giving f = Cl × C mg min−1.
Thus the concentration at equilibrium is determined
by the ratio of the infusion rate to the clearance of the
drug (C = f /Cl mg ml−1). The plasma concentration will
remain unchanged as long as the infusion rate is held
constant.
The body is depicted as a kinetically homoge-
neous unit assumes that the drug achieves instanta- Bolus-primed continuous infusion
neous distribution throughout the body and that the If an infusion is started at the rate needed to
drug equilibrates instantaneously between tissues. achieve the required plasma concentration it would take
Thus the drug concentration–time profile shows a about three time constants (or five half-lives) to reach
monophasic response i.e. it is monoexponential that concentration. This is usually too long for most
Constant rate infusion circumstances where infusions are needed. Instead, a
bolus dose of drug is given and the infusion started at
When an i.v. infusion is started at a constant rate our calculated rate. The size of the bolus dose should
of f mg min−1 in a simple one-compartment model, there be enough to fill the volume of distribution; for the
is no drug present initially, so plasma concentration (C)

simple one-compartment model this would be Ce/V,

where Ce is the required equilibrium concentration.
Stopping the infusion
If the infusion is stopped after reaching equilib-
rium, the decline in plasma concentration for this simple
model will follow a simple single exponential curve.
The time constant will be that for excretion. The decay
curve will have the same time constant (and half-life) for
both constant and bolus-primed infusions, even if the
infusion is stopped before equilibrium is reached. This
is because, in this simple model, the handling of drug
by the body can be described as a single exponential
process, and, independent of the duration of infusion,
it will always take the same time for the plasma con-
centration to halve.
Two-compartment model
The two-compartment model resolves the body
into a central compartment and a peripheral compart-
ment these compartments have no physiological or
anatomical meaning, it is assumed that the central
compartment comprises tissues that are highly per-
fused such as heart, lungs, kidneys, liver and brain.
The peripheral compartment comprises less well-
perfused tissues such as muscle,fat and skin. A
The drug concentration–time profile shows a
two-compartment model assumes that, following drug
curve but the log drug concentration–time plot shows
administration into the central compartment, the drug
a biphasic response there is a rapid decline in the drug
distributes between that compartment and the periph-
concentration owing to elimination from the central
eral compartment. However, the drug does not achieve
compartment and distribution to the peripheral compart-
instantaneous distribution, i.e. equilibration, between
ment then a slow decline as the drug gets eliminated.
the two compartments.
Hence during this rapid initial phase the drug concentra-
tion will decline rapidly from the central compartment,
rise to a maximum in the peripheral compartment, and
then decline.
Multicompartment model
In this model the drug distributes into more than
one compartment and the concentration–time profile
shows more than one exponential. Each exponential
on the concentration–time profile describes a compart-
ment.

The central compartment has a volume V1 and to drug concentration. By using this hydraulic model
the peripheral compartments volumes V2 and V3. The we can follow the processes that decrease drug con-
sizes of these vary from drug to drug and are influenced centration over time after bolus injection. Initially, drug
by physiochemical properties of the drug such as flows from the central compartment to both peripheral
lipid solubility. The rate constants for elimination from compartments via intercompartmental clearance and
plasma: k10 represents excretion, and k12 and k13 repre- completely out of the model via metabolic clearance.
sent distribution to compartments 2 and 3, respectively.
In addition, k21 and k31 represent movement of a drug
back into the central compartment once concentration
gradients are reversed. Clearances: attributable to
excretion (V1 · k10) and inter-compartmental clearances
between compartments 1 and 2 (V1 · k12 = V2 · k21) and
1 and 3 (V1 · k13 = V3 · k31). A drug may only enter and
leave the model through the central compartment. The
presence of three distinct phases after bolus injection
is a defining characteristic of a mammillary model with
three compartments. It is possible to develop hydraulic
models for intravenous drugs. In this model, there are
three tanks corresponding (from left to right) to the
slowly equilibrating peripheral compartment, the central
compartment (the plasma, into which drug is injected), Because there are three places for drug to go, the
and the rapidly equilibrating peripheral compartment. concentration in the central compartment decreases
The horizontal pipes represent intercompartmental very rapidly as represented by the solid line due to
clearance or (for the pipe draining onto the page) redistribution to the rapidly equilibrating compartment
metabolic clearance. The volumes of each tank cor- called the “rapid-distribution” phase. At the transition
respond to the volumes of the compartments for the between the solid line and the dashed line, there is
drug. The cross-sectional areas of the pipes correlate a change in the role of the most rapidly equilibrating
with fentanyl systemic and intercompartmental clear- compartment. At this transition, a second “slow-distri-
ance. The height of water in each tank corresponds bution” phase (dashed line in Fig) that is characterized

by movement of drug into more slowly equilibrating concentration in the brain to rise sufficiently to induce
tissues and return of drug to plasma from the most unconsciousness. This delay between peak plasma
rapidly equilibrating tissues. the concentration in the concentration and peak concentration at the effect site
central compartment falls below the concentration in is called hysteresis. Hysteresis is the clinical manifesta-
the rapidly equilibrating compartment, and the direction tion of the fact that plasma is not the site of anesthetic
of flow between them is reversed. The terminal phase action, only the mechanism of transport. Drugs exert
(dotted line in Fig) is a straight line when plotted on their pharmacologic effect in the biophase, which is also
a semilogarithmic graph. The terminal phase is often called the “effect site.” Physically, the biophase is the
called the “elimination phase” because the primary immediate milieu in which the drug acts on the body,
mechanism for decreasing drug concentration during including membranes, receptors, and enzymes.
the terminal phase is elimination of drug from the body.
The concentration of drug in the biophase cannot
Once the concentration in the central compartment falls
be measured for two reasons. First, it is usually inac-
below both the rapidly and slowly equilibrating compart-
cessible, at least in human subjects. Second, even if
ments (dotted line), the only method of decreasing the
we could take tissue samples, the drug concentration in
plasma concentration is metabolic clearance, the drain
the microscopic environment of the receptive molecules
pipe. Return of drug from both peripheral compartments
would not be the same as the concentration measured
to the central compartment greatly slows the rate of
in, for example, homogenated brain. Although it is
decrease in plasma drug concentration.
not possible to actually measure drug concentration
It is assumed for modelling purposes that the link in the biophase, we can characterize the time course
between pharmacokinetics and pharmacodynamics is of drug effect by using rapid measures of drug effect.
through the concentration of drug at the effector site. For neuromuscular blockers, the twitch response is
The effect compartment is not included in the model, an ideal measure of effect. For opioids and hypnotics,
as it does not remove a significant amount of drug from the measure of effect is more challenging. Analgesia
the plasma. However, there is a half-life for equilibra- and Hypnosis are subjective measures that are diffi-
tion (t1/2 keo) resulting in a time-lag before concentration cult to monitor and quantify moment by moment. The
changes in plasma are reflected in the effect compart- time course for equilibration between plasma and the
ment. This produces a delay in both onset and offset biophase is determined by using the spectral edge of
of pharmacodynamic effect when infusion rates are the EEG as the measure of effect. The BIS seems
changed. to have reasonable close correlation between brain
concentration of these drugs.
All pharmacokinetic parameters take constant
values only for a given patient under a given set of clini- Action of drug at the Biophase is determined by
cal circumstances; as soon as pathological processes the time for peak effect of a drug at effector site( ke0)
affect the body, these parameters will change. This is and the time required for the biophase concentration
of particular relevance when considering the behaviour to reach 50% of the plasma concentration (t ½ ke0) can
of drugs given by continuous infusion in critically ill be calculated as 0.693/ke0. After a bolus dose, the time
patients. to peak biophase concentration is a function of both
plasma pharmacokinetics and ke0.
Pharmacodynamic considerations
t ½ keo = 0.693/ keo , the rate constant for transfer of drug
The biophase
from the site of drug effect to the environment.
The plasma concentration after an intravenous
The time to peak effect (ke0) and the t ½ ke0 for
bolus peaks nearly instantaneously in the plasma con-
several intravenous anesthetics has been estimated
centration but additional time is required for the drug

Drug Time to Peak Drug Effect ke0 t ½ ke0 after a Bolus Dose (min)
(min)
Fentanyl 3.6 4.7
Alfentanil 1.4 0.9
Sufentanil 5.6 3.0
Remifentanil 1.6 1.3
Propofol 2.2 2.4
Thiopentone 1.6 1.5
Midazolam 2.8 4.0
Etomidate 2.0 1.5
Dose implications of the biophase coincides with endotracheal intubation. However, for
a slower induction in which a nondepolarizing neuro-
The delay in onset has important clinical implica-
muscular blocking drug is used, it may be appropriate
tions. After a bolus, the plasma concentration peaks
to choose an opioid with a slower onset of drug effect
nearly instantly and then declines steadily. The effect-
to coincide with the peak effect of the muscle relaxant.
site concentration starts at zero and increases over
In this case, a bolus of fentanyl or sufentanil at the time
time until it equals the descending plasma concentra-
of induction may be more appropriate.
tion. The plasma concentration continues to decline,
and after the moment of identical concentrations, the
gradient between plasma and the effect site favours
removal of drug from the effect site, and the effect-site
concentration decreases. The rate at which the effect
site rises toward the peak after a bolus dictates how
much drug must be injected into plasma to produce a
given effect. For alfentanil, its rapid plasma effect-site
equilibration (large ke0) causes the effect-site concen-
tration to rise rapidly, with a peak produced in about
90 seconds. At the time of the peak, about 60% of the
alfentanil bolus has been distributed into peripheral
tissues or eliminated from the body. For fentanyl, the
effect site concentration rises much more slowly and
peaks 3 to 4 minutes after the bolus. At the time of the
peak, more than 80% of the initial bolus of fentanyl has The time to peak effect for the commonly used
been distributed into tissues or eliminated. As a result of opioids is shown above
slower equilibration with the effect site, relatively more Knowing ke0 (or time to peak effect) also improves
fentanyl than alfentanil must be injected into plasma, titration of the drug by identifying the time at which the
which makes the rate of offset of drug effect after a clinician should make an assessment of drug effect.
fentanyl bolus slower than after an alfentanil bolus. For example, midazolam has a slow time to peak effect,
This difference in pharmacokinetics suggests that and repeat bolus doses should be spaced at least 3 to
ke0 must be incorporated into dosing strategies. For 5 minutes apart to avoid inadvertent overdosing.
rapid onset of effect, a drug with a large ke0 (short t ½ Designing dosing regimens
ke0 ) should be chosen.
Bolus dose calculations
For example, for rapid-sequence induction, al-
fentanil or remifentanil may be the opioid of choice The definition of concentration is amount divided
because the peak opioid effect-site concentration by volume. Rearrangement of the definition of concen-
tration can help to find the amount of drug required

to produce any desired concentration for a known of drug effect. The size of this volume can readily be
volume calculated from the observation that the plasma and
effect-site concentrations are the same at the time of
Amount = CT x Volume, where CT is the desired or
peak effect:
“target” concentration. The problem with applying this
concept to anesthetic drugs is that there are several Vdpe = Bolus Amount / Cpe where Cpe is the plasma
volumes: V1 (central compartment), V2 and V3 (the concentration at the time of peak effect.
peripheral compartments), and Vdss, the sum of the
Rearranging the equation by substituting CT, the
individual volumes. V1 is usually much smaller than
target concentration (which is the same in plasma and
Vdss, and thus it is tempting to say that the loading dose
the effect site at the moment of peak effect), for Cpe to
should be something between CT × V1 and CT × Vdss.
calculate the size of the initial bolus:
The C50 for fentanyl, combined with thiopental
Loading Dose = CT x Vdpe
for intubation, is approximately 3 ng/mL. The V1 and
Vdss for fentanyl are 13 and 360 L, respectively. An The Vdpe for fentanyl is 75 L. To achieve a peak
appropriate dose of fentanyl to attenuate the hemo- fentanyl effect-site concentration of 3.0 ng/mL requires
dynamic response is between 39 μg (3 ng/mL × 13 L) 225 μg, which produces a peak effect in 3.6 minutes.
and 1080 μg (3 ng/mL × 360 L). A fentanyl bolus of This is a much more reasonable dosing guideline than
39 μg achieves the desired concentration in plasma the previous recommendation of a dose between 39
for an initial instant, but plasma levels almost instantly and 1080 μg.
decrease below the desired target. Levels at the effect Volume of distribution at the time of peak effect
site will never be close to the desired target concentra-
tion of 3 ng/mL. A fentanyl bolus of 1080 μg, produces Drug V1 (L) Vdpe (L)
a marked overshoot in plasma levels that persists for Fentanyl 12.7 75
Alfentanil 2.19 5.9
hours. Plasma is not the site of drug effect. The ke0 of an
Sufentanil 17.8 89
intravenous anesthetic helps design a dosing regimen
Remifentanil 5.0 17
that yields the desired concentration at the site of drug Propofol 6.7 37
effect. Overdosing is avoided by selecting a bolus that Thiopentone 5.6 14.6
produces the desired peak concentration at the effect Midazolam 3.4 31
site.
This introduces the concept of Vdpe, the appar- The target concentration in the effect site is the
ent volume of distribution at the time of peak effect, same as the target concentration in plasma at steady
or pseudo-equilibration between plasma and the site state. The target concentration is influenced by patient
physiology, surgical stimulation, and concurrent drug
administration. When using an opioid and hypnotic
combination dose is set so as to properly account
for the synergy between them. To achieve an effec-
tive target concentration, the conventional teaching
of administering a loading dose calculated as target
concentration times volume of distribution, followed by
a maintenance rate calculated as target concentration
times clearance, is inaccurate. The initial loading dose
may be calculated as the target concentration times
the volume of distribution at peak effect. Maintenance
rates must initially account for distribution of drug in
peripheral tissues and are turned down to the target
concentration times clearance only after equilibration
with peripheral tissues.

Maintenance infusion rates
To maintain a given target concentration, CT, drug

must be delivered at the same rate that it is exiting the
body, the rate at which drug exits the body is systemic
clearance, ClS, times the plasma concentration.
= CT x Cls
For drugs with multicompartmental pharmacoki-
netics, which includes all of the intravenous drugs
used in anesthetic practice, drug is distributed into the For example, to maintain a fentanyl concentration
peripheral tissues as well as cleared from the body. of 1.5 ng/mL, the appropriate rates are 4.5 μg/kg/hr at
The rate of distribution into tissues changes over time 15 minutes, 3.6 μg/kg/hr at 30 minutes, 2.7 μg/kg/hr at
as the tissues equilibrate with plasma. So the above 60 minutes, 2.1 μg/kg/hr at 120 minutes, and 1.5 μg/
calculation is correct only after the peripheral tissues kg/hr at 180 minutes. Infusion rates are appropriately
have fully equilibrated with plasma, which requires adjusted based on the clinical judgement of the surgical
many hours. At all other times, this maintenance infu- circumstances.
sion rate underestimates the infusion rate to maintain Another recent approach to manually determine
a target concentration. Because the net flow of drug infusion rates for maintenance of anesthesia to a de-
into peripheral tissues decreases over time, the infu- sired target concentration is through the application of
sion rate required to maintain any desired concentra- concepts involving the use of a slide rule. As described
tion must also decrease over time. The infusion rates by Bruhn and colleagues, the bolus dose required
at different times necessary to maintain any desired to reach a given target plasma concentration is the
concentration of various anesthetic drugs has been product of the (weight-related) distribution volume and
well established. required concentration. Similarly, the infusion rate at a
particular time point is the product of target concentra-
tion, body weight, and a correction factor that depends
on the time elapsed from the start of the initial infusion.
When compared with computer simulation programs,
this manual device performed within an acceptable
degree of accuracy (within 7% of the simulated target
concentration) for a single target concentration and
decreased in accuracy (within 20%) when applied to
changing target concentrations.

Recovery from anesthesia movement, hypertension, release of catecholamines)

to a particular stimulus (e.g., incision, intubation, sternal
Recovery from anesthesia is determined by the
spreading) in 50% of patients
pharmacokinetic principles that govern the rate of
decrease in drug from the effect compartment once The C50 for depression of the electroencephalo-
drug administration is terminated, as well as by the gram (EEG) is the steady-state serum concentration
pharmacodynamics of the drug. The rate at which that causes a 50% slowing of the maximal EEG is used
drug decreases is dependent on both elimination and for all IV anesthetics, except for midazolam, where the
redistribution of the drug from the central compartment, C50 is associated with 50% activation of the EEG. The
which in turn varies according to the duration for which C50 for skin incision is the steady-state plasma concen-
the drug has been administered. tration that prevents a somatic or autonomic response
in 50% of patients. The C50 for loss of consciousness
Drug potency
is the steady-state plasma concentration for absence
The pharmacokinetics and pharmacodynamics of of a response to a verbal command in 50% of patients.
inhaled anesthetics is defined by an well established The C50 for spontaneous ventilation is the steady-state
entity called MAC. The pharmacodynamics of intrave- plasma concentration associated with adequate spon-
nous anesthetics is reported in terms of C50, the con- taneous ventilation in 50% of patients
centration that produces 50% of the maximum possible
Steady state concentrations of pre-defined effects
drug effect. C50 could mean several end points includ-
of several drugs has been studied
ing, drug concentration that prevents response (e.g.,
Drug C50 for C50 for C50 for C50 for C50 for MEAC
EEG Incision Loss of Spont Isoflurane
Depression /Painful consciousness Vent MAC
stimuli reduction
Propofol 3–4 4-8 2-3 1.33 - -
(μg/ml)
Thiopentol 15 – 20 35 - 40 8 - 16 - - -
(μg/ml)
Midazolam 250 - 350 - 125 - 250 - - -
(ng/ml)
Alfentanil 500 - 600 200 - 300 - 170 - 230 50 10 - 30
(ng/ml)
Fentanyl 6 - 10 4-6 - 2-3 1.7 0.5 - 1
(ng/ml)
Sufentanil 0.5 – 0.75 0.3 – 0.4 - 0.15 – 0.2 0.15 0.025 –
(ng/ml) 0.05
Remifentanil 10 - 15 4-6 - 2-3 1.2 0.5 - 1
(ng/ml)
MEAC is the minimum effective plasma concentration for several end points: loss of response to intubation,
providing post-operative analgesia. loss of response to intraoperative stimulation, and
emergence from anesthesia. The most profound
C50 for combination of drugs has also been defined
stimulation was tracheal intubation, and abolition of
like alfentanil in the presence of 66% nitrous oxide for
that stimulus required a propofol concentration of at
several noxious stimuli. Vuyk and colleagues charac-
least 2 μg/mL.
terized the interaction between propofol and alfentanil

Context-sensitive half-time
The plasma concentration to decrease by 50%
from an infusion that maintains a constant concen-
tration has been termed the “context-sensitive
half-time” with the context being the duration of the
infusion.
On stopping an infusion, three possible processes
contribute to a decline in plasma concentration: dis-
tribution to the second and third compartments, and
excretion. The relative contributions of these to the
initial decline in plasma concentration vary according
to the duration of the infusion. The longer the infusion,
the lower the concentration gradients between plasma
The relationship between opioids and hypnotics
(central compartment) and compartments 2 and 3, so
on the C50, the concentration of drug associated with
the lower the contribution of distribution to elimina-
50% of maximum effect, has been examined. The
tion. After a very short infusion, plasma concentration
interaction between two drugs describes a surface in
will fall to half the initial concentration in a very short
which each drug has its own axis and the third axis is
time, due to the combined effects of distribution and
the effect from any combination of the two drugs. The
excretion. If the infusion runs to equilibrium, there is
relationship is depicted between the three-dimensional
no contribution from distribution and elimination occurs
response surfaces and the more commonly shown
only by excretion, which is opposed by re-distribution
relationship in two dimensions between the C50 of
from peripheral compartments. Thus, the longest time
two drugs. Minto and colleagues published “response
for plasma concentrations to halve will occur following
surfaces” for combinations of midazolam-alfentanil,
equilibrium when, with some drugs such as fentanyl,
propofol-alfentanil, and midazolam-propofol associated
it may come close to terminal elimination half-life. For
with loss of response to verbal command.
infusions of intermediate duration, the time for the
plasma concentration to halve will be between these
two extreme values. This ‘halving time’ is known as
the context-sensitive half-time where the ‘context’
is the duration of the infusion.
The time for plasma concentration to halve again
(i.e. from a half to a quarter of the concentration on
stopping the infusion) is longer than the context-sen-
sitive half-time, so these are not half-lives (which are
constants) but half-times. The time to reach maximum
context-sensitive half-time depends largely on (Vdss)and
rate constant for re-distribution; it is shortest for drugs
with a low (Vdss)and low rate constant for redistribution
(e.g. remifentanil) and longest for large (Vdss)and high
rate constant for redistribution (e.g. fentanyl).
Continuous infusions of propofol, alfentanil, fenta-
nyl and remifentanil are used commonly in anesthesia.
Not only do they have very different context-sensitive
half-times, but they also show very different patterns of

changes in context-sensitive half-time as infusion time term is the context-sensitive decrement time in which
increases. Propofol has a context-sensitive half-time the decrement in concentration is specifically noted, as
that varies between 3 min for a very short infusion to is the compartment where the decrease is modeled
about 18 min after a 12-h infusion. This relatively small (plasma or effect site). For example, the relationship
variation in context-sensitive half-time, despite a large between infusion duration and time required for a 70%
V3, occurs because excretion is rapid compared with decrease in fentanyl effect-site concentration is the
redistribution. For weak acids and bases, the degree of “context-sensitive 70% effect-site decrement time.”
ionization influences pharmacokinetics. The lower pKa To awaken a patient we have to decide when to ter-
of alfentanil (6.4) compared with fentanyl (8.5) means minate the infusion. The decrease in concentration
that the concentration of the un-ionized, diffusible form necessary for recovery, the duration of the infusion (the
of alfentanil is 100 times greater than that of fentanyl. context), and the context-sensitive effect-site decre-
This accounts for its rapid onset-time and short t1/2 keo. ment time required for the necessary decrease need
For modelling purposes, alfentanil has a smaller central to be factored. Context-sensitive decrement times are
compartment volume, a very much lower (Vdss)and a fundamentally different from the elimination half-life.
lower clearance than fentanyl. As a result of these With monoexponential decay, each 50% decrease in
differences, fentanyl has a shorter context-sensitive concentration requires the same amount of time, and
half-time than alfentanil for short infusions (<2 h). How- this time is independent of how the drug is given. This is
ever, alfentanil reaches its maximum context-sensitive not true for the context-sensitive half-time. First, as the
half-time after just 90 min, so has a very much shorter name is intended to imply, the time needed for a 50%
context-sensitive half-time than fentanyl after very long decrease is absolutely dependent on how the drug was
infusions. Fentanyl becomes a very long acting drug if given, with infusion duration being the context to which
given at high infusion rates for many hours because it the name refers the time needed for a 50% decrease
has a large V3 and redistribution is rapid , thus plasma is absolutely dependent on how the drug was given,
concentrations are maintained despite rapid excretion. with infusion duration being the context to which the
Remifentanil has a relatively constant context-sensitive name refers.
half-time. This is because clearance attributable to
Infusion devices
excretion (ester hydrolysis) is very high and (Vdss) is
much smaller than for other opioids. Manual delivery
When an infusion of an intravenous anesthetic
is administered, the infusion regimen can be con-
trolled by a variety of mechanisms varying from the
simple devices like Dial-a-Flow to complex computer-
controlled infusion pumps. Simplicity of mechanical
design, however, is not necessarily correlated with
ease of use. The most commonly used pumps for
administration of intravenous anesthetics are posi-
tive displacement syringe pumps that use a variety
of mechanisms. An important advance has been the
introduction of a calculator feature within the pump
so that the clinician can set the weight of the patient,
the drug concentration, and the infusion rate in dose/
A 50% reduction in drug concentration appears unit weight/unit time and the pump will then calculate
to be necessary for recovery after the administration the infusion in volume/unit time. These pumps also
of most intravenous hypnotics at the termination of permit simple application of a staged infusion scheme
surgery. Depending on circumstances, decreases other (e.g., the two-stage approach of Wagner by allowing
than 50% may be clinically relevant. A more general

a loading dose and a maintenance infusion rate to be in their response to a given drug dose or concentration,
programmed into the pump. Numerous syringe pumps and it is therefore essential to titrate to an adequate
also now include automated recognition of syringe drug level for each individual patient. Drug concentra-
size. Intravenous anesthetics via conventional infusion tions required to provide adequate anesthesia also vary
pumps must be delivered in doses based on integrated according to the type of surgery (e.g., surface surgery
pharmacokinetic-pharmacodynamic models. However, versus upper abdominal surgery). The end of surgery
it is the patient’s response, demonstrating adequate or requires lower drug levels, and hence titration often
inadequate anesthesia, that ultimately determines the involves judicious lowering of the infusion rate toward
rate of drug administration. Individuals vary markedly the end of surgery to facilitate rapid recovery.
Manual infusion schemes
If the infusion rate proves to be insufficient to Therefore, the infusion scheme should be tailored to
maintain adequate anesthesia, both an additional provide peak concentrations during these brief periods
loading (bolus) dose and an increase in infusion are of intense stimulation. An adequate drug level for en-
required to rapidly raise the plasma (biophase) drug dotracheal intubation is often achieved with the initial
concentration. Various interventions also require loading dose, but for procedures such as skin incision,
greater drug concentrations, usually for brief periods a further bolus dose may be necessary. This level of
(e.g., laryngoscopy, endotracheal intubation, skin inci- precision can be achieved by using TCI devices. Such
sion) devices go beyond simple calculator pumps to the cre-
ation of pumps with automated drug delivery.
Automated Delivery

• CCIP – Computer Controlled Infusion Pump.

The acronym TCI (Target Controlled Infusion) is
now used as a broader term to describe the technique
for the continuous control of the concentration in blood
or plasma of infused drug. TCI involves the use of a
microprocessor to manage the pump. Instead of setting
an infusion rate in terms of mg/kg/h, the anaesthetist
enters the following:
• Body weight of the patient
Definition of Target Controlled Infusion (TCI) • Age of the patient
When applied to anesthesia,TCI is an infusion Required blood concentration of the drug (= target
system which allows the anesthetist to select the target blood concentration in μg/ml).
blood concentration required for a particular effect, and
then to control depth of anesthesia by adjusting the
requested target concentration.
Target controlled infusion (TCI) is a logical ap-
proach to the development of improved administration
techniques for an intravenous anesthetic agent. TCI is
based on an understanding of the agent’s pharmacoki-
netic properties.
Choosing a drug and a pharmacokinetic model
The basic rationale for Target Controlled Infusion
(TCI) of an intravenous anesthetic agent is to enable
the anaesthetist to alter the depth of anesthesia in as
simple a manner as using standard volatile anesthetics
delivered via calibrated vaporizers. With TCI, induc-
Based on computer simulation and a direct com-
tion and maintenance are a continuous process with
parison of predicted values with measured values
a single agent unlike the separate use of an intrave-
obtained from a study in which the same infusion
nous agent for induction and an inhalational agent for profile was used in all patients the “Marsh” model was
maintenance. Researchers have referred to the basic selected for the development of ‘Diprifusor. Other
concept of utilising a pharmacokinetic model and mi- models available for Propofol TCI include Schneider
croprocessor (= computer) to control an infusion pump, model, Shafer, Gepts, Kirkpatrick, Cock-shott and
by the following acronyms: Tackley models. For the opioids, a better consensus
• CATIA – Computer Assisted Total Intravenous exists than for propofol, and so only one model for re-
Anesthesia mifentanil (‘Minto’), sufentanil (‘Gepts’), and alfentanil
(‘Maitre’) has been selected for use in commercially
• TIAC – Titration of Intravenous Agents by
available TCI systems.
Computer
Standardisation and validation of pharmacokinetic
• CACI – Computer Assisted Continuous Infu- parameters are essential for the clinical application of a
sion TCI system. Marsh model parameters are as follows

V1 Volume of central compartment 228 ml kg-1

k10 Elimination rate constant from the central compartment 0.119 min -1
keo Elimination rate constant from the effect compartment 0.26 min -1
INTERCOMPARTMENTAL DISTRIBUTION RATE CONSTANTS
k12 FROM V1 TO V2 0.114 min -1
k21 FROM V2 TO V1 0.055 min -1
k13 FROM V1 TO V3 0.0419 min -1
k31 FROM V3 TO V1 0.0033 min -1
Induction time is related to the speed of injection. Target blood concentrations of propofol should
For instance, with a fixed dose of 2.5 mg/kg, mean be titrated against the response of the patient in order
induction time was 30.8 seconds with an injection to achieve the depth of anesthesia required
time of 20 seconds and 58.4 seconds with an injection
• In adults (under 55 years of age), anesthesia
time of 80 seconds. The anesthetic endpoint of loss of
can usually be induced with target concentra-
consciousness (loss of response to verbal or tactile
tions of 4 to 8 μg/ml
stimuli) occurred in 50% of patients with plasma con-
centrations (Cp50 or EC50) ranging from 2.7 to 3.4 μg/ • In premedicated patients, an initial target
ml. Infusion rates have been adjusted manually within concentration of 4 μg/ml is advised
a typical range of 4 to 12 mg/kg/h. A linear relationship • In unpremedicated patients an initial target
between the infusion rate of propofol and steady-state concentration of 6 μg/ml is advised
blood concentrations has been demonstrated; with
• Induction time with these targets is generally
continuous infusions of 3, 6 or 9 mg/kg/h for at least
within the range of 60 to 120 seconds
2 hours, blood concentrations were 2.1, 3.6 and 5.9
μg/ml. Measurements of blood concentrations during • A lower initial target concentration should be
recovery after propofol infusion have demonstrated used in patients over the age of about 55 years
that patients awaken when concentrations are in the and in patients of ASA grades III or IV.
region of 1 to 2 μg/ml.
Maintenance target concentration in TCI marsh protocol
Patient type Mean maintenance target concentration

Healthy adult patient 3.5 – 5.3 ȝg/ml
ASA 1 & 2
Cardiac patient 2.8 – 3.4 ȝg/ml
ASA 2, 3 & 4
Age > 55 years 3.5 ȝg/ml
Development of concept and terminology • “Communication” system between “control unit”

Key components – basic software and hardware and infusion pump
• Pharmacokinetics – a validated model with spe- • User interface for input of patient data and target
cific parameters for drug blood concentration
• Algorithm(s) to control infusion rate Considerations for development of a commercial

system
• “Control unit” i.e. software and microprocessors
for above • Standardisation of the pharmacokinetic model for
a particular drug
• Infusion pump

• Validation of the system software and production The TCI system maintains the blood concentration
processes until a new target is set by the anaesthetist. TCI is not
a system for the complete computer control of anes-
• Safety mechanisms in the unlikely event of mal-
thesia. When using TCI, the anaesthetist adjusts the
function of components
target blood concentration of drug and titrates to clini-
• Integration of basic software and hardware with cal effect. A TCI system is a convenient tool to assist
infusion pump to provide a reliable and portable the anaesthetist in adjusting the depth of anesthesia.
unit Control still rests with the anaesthetist, who uses clini-
• User interface to be as simple to operate as the cal signs or more sophisticated means of monitoring.
controls of a vaporizer Titration of the target concentration and therefore
• Convenient syringe presentation of drug the depth of anesthesia is rapid and predictable with a
TCI system. Target concentration is readily increased
• Documentation (e.g. prescribing information, user
in anticipation of stimulating events (e.g. placement of
guides) for drug and device
laryngeal mask airway or surgical incision). Similarly,
• Automatic recognition device for correct drug target concentration can be readily decreased to tailor
identification and usage the level of anesthesia needed towards the end of
surgery. With TCI, there is a constantly changing dis-
Software in the microprocessor incorporates a
play of calculated (or predicted) blood concentration.
pharmacokinetic model and a specific set of parameters
The system may also provide information on the time
for the drug to be infused. The microprocessor continu-
required to reach the desired target concentration.
ously calculates the variable infusion rates required to
achieve a predicted blood concentration. An algorithm Some systems have the facility to display the
controls the operation of the infusion pump so that propofol concentration calculated to exist at the
infusion rates are altered automatically to achieve this effect-site in the brain which helps address the issue
blood concentration. of hysteresis. Some TCI systems have the facility to

display predictive information about the time required to • Weight of patient

achieve a lower calculated concentration if the infusion
• Target concentration.
were to be stopped (decrement time). The anesthetist
can then easily modify drug administration to optimise Benefits of TCI
the speed of recovery. When an infusion is interrupted Clinical benefits of TCI
(e.g. for a change of syringe), a TCI system may make
• Short time to recovery
automatic compensation. When infusion stops, the
system continues to predict the blood concentration. • Low incidence of PONV
Infusion rates do not need to be calculated when using
• Short time to discharge
a TCI system.
Economic effects
The anesthetist simply selects a target blood con-
centration. The system makes continuous calculations • Saves nursing time in the recovery room
and controls the rate of drug infusion so as to achieve • Limits the need for anti-emetic therapy
and maintain the requested target concentration – and
• Allows patients an early return to work
the desired level of anesthesia.
Convenience in use
The initial target concentration required to induce
anesthesia is selected according to age, ASA status, Practical aspects
premedication and supplementary analgesic admin- • Simple to operate
istration. Response to the initial target concentration
may be used as a guide to subsequent requirements, • Easy to titrate the level of anesthesia
including during the maintenance phase. TCI allows the • Displays calculated blood or plasma concen-
anaesthetist to make small (e.g. 0.1 μg/ml) as well as trations
large changes (e.g. 1 μg/ml) to target concentration at
• Compensates for interrupted infusion
any time. Stimulating events (e.g. surgical incision) may
be anticipated by increasing the target concentration. • Avoids the need for time-consuming calcula-
Decreases in target concentrations may be required in tions
response to events such as a fall in blood pressure.
• Continuous process from induction through to
The default setting of target concentration is 4 μg/ maintenance
ml.
• Control of anesthesia
• Effect-site concentration (calculated)
• Theoretical aspects
• Time to target (calculated)
• Good control of depth of anesthesia
• Time to lower target (calculated decrement
• Gives stable anesthesia
time)
• Improved control of cardiovascular and respira-
• Patient details (inputted age and weight). A
tory parameters
control knob is used to dial up the following
inputs: • Induction phase can be used to predict main-
tenance effects
• Age of patient

CLINICAL LECTURES


Controversies in Obstetric Anesthesia 70 Sunanda Gupta
01 CONTROVERSIES IN OBSTETRIC ANESTHESIA
Prof and Head, Sunanda Gupta

RNT Medical College,
Udaipur
Controversies in obstetric anesthesia and anal- to better maternal satisfaction, reduced breakthrough
gesia are difficult to resolve due to several reasons. pain without increasing the epidural local anesthetic
Ethical considerations often preclude the initiation of consumption. The introduction of background auto-
prospective, randomized studies so that most authors mated mandatory bolus to a PCEA , demonstrated a
have to rely on retrospective studies of patient records, local anesthetic sparing effect and a reduction in the
disregarding selection bias and the multiplicity of un- incidence of manual rescue boluses, while another
controlled variables. Juxtaposition of animal studies, technique of ‘programmed intermittent mandatory epi-
although allowing for more controlled variables, is dural bolus’ with PCEA regimen is said to be superior
again not clinically applicable due to species differ- to the former technique in terms of reducing local an-
ences and the drug dose chosen. However, for the esthetic consumption and incidence of breakthrough
clinician, a review of the available information may be pain.
of assistance, which can highlight new hypothesis and
Prolongation of labour
areas for future research though a consensus on man-
agement of controversial areas is difficult. This review Epidural analgesia was considered to be associ-
will address some of the controversial issues related ated with a prolongation of first stage of labor by an
to labour analgesia and anesthesia during caesarean average of 42 min and a prolongation of the second
section. stage of labour by an average of 14min. The recent Co-
chrane review 2010, found no evidence of a significant
I. Obstetric analgesia
difference in prolongation of the first stage between
Maintaining neuraxial analgesia neuraxial and non-neuraxial analgesia outcome (WMD
23.81 minutes, 95% CI -18.88 to 66.51). Length of sec-
Many different techniques to maintain epidural
ond stage of labour was found to be longer in eleven
labour analgesia with a view to improve analgesia,
trials involving 3580 women where women with epidural
reduce breakthrough pain, reduce physician workload
analgesia had a statistically significant longer second
and decrease local anesthetic consumption have been
stage of labour as compared to women receiving non
introduced in recent times. A PCEA combined with a 4
neuraxial analgesia (WMD 15.55 minutes, 95% CI 7.46
ml/hr background infusion has been found to produce
to 23.63, 11 trials, 3580 women).
fewer episodes of visual analogue pain scores > 4 ⁄ 10
and fewer boluses requested and delivered . Incidence of instrumental delivery
However, there is still no clear consensus as to The rate of instrument-assisted vaginal delivery
the ideal background infusion rates as higher infusion is of concern because it is consistently associated with
rates of >5ml/h are found to be efficient in terms of a higher rate of serious perineal laceration, which has
PCEA efficiency but lead to greater local anesthetic been implicated as a risk factor for later fecal inconti-
consumption. Another recent development is the use nence. Instrument-assisted vaginal deliveries have also
of computer-integrated PCEA, which enables a PCEA been linked to higher rates of birth injuries. The most
pump, connected to a computer, to titrate the back- recent randomized trial found an increase in the rate of
ground infusion rate based on PCEA demands. It has deliveries involving forceps from 3 percent in the opioid
been found that as labour progresses, the requirement group to 12 percent in the epidural- analgesia group.
of CI-PCEA (computer integrated patient controlled However, the reason for this increase with epidural
epidural analgesia) infusion rates is increased, leading analgesia remains unclear. One hypothesis is that the

motor blockade may prevent the mother from push- CSE for initiation of labour analgesia and FHR
ing and thereby necessitate the use of instruments. abnormalities
Epidural analgesia is also associated with a higher
Newer techniques that have established them-
frequency of the occiput posterior position of the fetus at
selves may not be quite as superior as they are initially
delivery, which, if causal, could represent a mechanism
thought to be, but are still followed in some centres
by which epidural analgesia contributes to the higher
as per the institutional protocols and specific indica-
rate of instrument-assisted delivery. It is also possible
tions. Several investigators have described episodes
that the presence of an epidural block may sometimes
of fetal heart rate (FHR) abnormalities following the
decrease the obstetrician’s threshold for performing
spinal injection of analgesic solutions. The investiga-
instrument-assisted deliveries, as well as for allowing
tors showed that the use of CSE analgesia was an
instrument-assisted delivery for the purposes of teach-
independent predictor of uterine hypertonus and that
ing residents. In the most recent Cochrane analysis
the only predictor of FHR abnormalities was an in-
2010, seventeen trials, involving 6162 women, reported
crease of 10 mmHg or more in baseline uterine tone.
this outcome. The risk of instrumental delivery was
The authors also demonstrated that a decrease in
greater in the women randomized to epidural analgesia
visual analogue pain scores independently predicted
compared with women randomized to non-epidural
a simultaneous occurrence of FHR abnormalities and
analgesia while there was no evidence of a statistically
uterine hypertony. The pathophysiological explanation
significant difference in the risk of caesarean section.
for this phenomenon has been ascribed to the spinal
Incidence of caesarean section block-induced rapid onset of analgesia, which results in
a sudden drop in plasma adrenaline and b-endorphins
Studies have consistently demonstrated an in-
but not of noradrenaline and oxytocin. The unopposed
crease in the rate of caesarean deliveries, with great
action of nor adrenaline leads to a decrease in utero-
variations in physician specific rates of CD as well as
placental circulation with FHR abnormalities.
the age of the parturient, suggesting that management
practices may have an important role. In the Cochrane Intrathecal administration of 2.5 mg bupivacaine
analysis, 2010 twenty trials, involving 6534 women, alone has been found to provide acceptable labour
reported this outcome. They found no increase in the analgesia within 5 min and for more than 30 min and
risk of CD (RR 1.07, 95% CI 0.93 to 1.23) for cervical at this dose, spinal bupivacaine does not cause sig-
dystocia, when comparing neuraxial and non neuraxial nificant motor blockade, maternal hypotension and
forms of analgesia. Therefore the question of whether fetal bradycardia. Initiating an epidural infusion that
the use of epidural analgesia for pain relief during contains opioids within 30 min following spinal injection,
labour increases the rate of caesarean deliveries in comparison to 60 min or more, has been shown to
performed because of a failure of labour to progress, reduce the incidence of breakthrough pain and to be
remains unanswered. However, on analyzing the risk safe. Taking this inference into consideration, perhaps
of CD for fetal distress among parturients with neuraxial a CSE with subarachnoid injection of local anesthetic
and non neuraxial analgesia in the Cochrane analysis without opioids followed by early initiation of epidural
2010, ten trials, involving 4421 women, reported this analgesia could provide satisfactory pain relief while
outcome. The point estimate showed a 42% increase minimising the risks of opioid-induced transient fetal
in the relative risk of caesarean section for fetal distress bradycardia. Further research to explore this theory is
in the epidural group with the confidence intervals close still awaited.
to statistical significance (RR 1.42, 95% CI 0.99 to
PDPH following CSE
2.03). On the contrary, the incidence of CD for dysto-
cia showed no significant difference between the two Although “common sense” may dictate that the
groups. incidence of PDPH should be more frequent with the
CSE technique because of the intentional dural punc-
ture, it has been established that the incidence of PDPH

is not greater with CSE. It has been suggested that of several nonrandomized trials are consistent with
the anesthesiologist may be more meticulous during these findings. Therefore, current data do not support
CSE placement, which may lead to a lower incidence a relation between a new onset of back pain and the
of accidental dural puncture, while the introduction of use of epidural analgesia during labor.
subarachnoid opioid may “provide prophylaxis” against
Infectious complications of neuraxial analgesia
the development of PDPH. It is also possible that the
epidural local anesthetic increases subarachnoid pres- Controversy has centred around infectious
sure, which may decrease the incidence of headache complications and their source, following neuraxial
following the CSE technique. analgesia, which though rare, may prove devastating.
The centers for disease control and prevention (CDC)
Effect on maternal temperature
in 2010, reported 5 cases of bacterial meningitis after
Labor epidural analgesia is associated with a intrapartum spinal analgesia, which underlined the
time-related maternal temperature increase or fever. importance of anesthesia practice. Out of these 4
Traditionally, it has been assumed that epidural analge- cases were attributed to droplet transmission directly
sia could attenuate hyperventilation and reduce lower from oropharynx or through contamination of sterile
body sweating through sympathetic blockade. Thus, equipment. Significantly the anesthesiologists involved
loss of heat dissipation during epidural analgesia may in the cases were implicated. This underscores the
allow heat retention especially under circumstances of importance of not only wearing a surgical mask, but
heightened energy production during labor. A recent also ensuring a proper fit covering the mouth and nose,
study, in which the incidence of fever at 4 h in the pa- changing masks between cases as recommended by
tients receiving intermittent epidural bolus injections ASA. Further directives include use of chlorhexidine
was significantly lower than those receiving continu- (preferably with alcohol) to paint the back, remove all
ous infusion provided further support for this assump- jewelry (rings, watches, bangles) wearing a mask, cap,
tion. Because women receiving boluses had a lower gloves with all aseptic precautions. Additional recom-
dermatome level than those in the infusion group, the mendations include sterile occlusive dressing at the
authors assumed intermittent recovery of dermatome catheter insertion site and limiting disconnection and
blockade level during analgesia might promote heat reconnection of neuraxial delivery systems.
loss and thus prevent fever (a physiological basis for
Pharmacogenetics
fever)
Pharmacogenetics, or the study of how genes
CSE has been found to show a significant in-
impact on the response to drugs, offers the potential to
crease in intrapartum temperature as compared to
tailor medications to each individual’s genetic profile.
non neuraxial analgesia in 14% vs none. The rationale
Some insight has been given into the genetic compo-
behind this increase is a theoretical imbalance between
nent of the analgesic response to intrathecal opioids
heat production and dissipation and on a disturbance
given in labor. While the way to routine genetic testing
in the central thermoregulation. However, this fever
to guide analgesic therapy is still a long one, a true
is not indicative of any increase in risk of maternal or
pharmacogenetic effect of the μ-opioid receptor gene
neonatal infection.
has been demonstrated that explains differences in
Back pain analgesic requirements observed routinely in obstetric
anesthesia practice. A significant increase in sensitivity
Many parturient women are concerned that
to the analgesic effect of intrathecal fentanyl in labor-
epidural analgesia may lead to back pain. A recent
ing women carrying a common variant of the μ-opioid
randomised trial studied 385 nulliparous parturient
receptor gene was shown. This demonstration of a 1.5
women for 12 months after delivery. No difference in
to 2-fold difference in analgesic requirement according
the incidence of backache could be demonstrated be-
to genotype is clinically relevant, because provision of
tween women who were randomly assigned to receive
optimal labor analgesia remains a challenge, with a
epidural analgesia and those who were not. The results

need to reduce doses and minimize opioid-related side Intravenous ergometrine 0.2–0.5 mg given slowly
effects. If confirmed in other clinical settings and with or by intramuscular injection, in the absence of contrain-
other opioids, use of μ-opioid receptor genotyping may dications, is the currently recommended second-line
improve the provision of analgesia in the not-too-distant therapy, Many clinicians use 15-methyl prostaglandin
future. F2ά, 250–500 μg intramyometrially, but this agent is
II. Obstetric anesthesia not licensed for administration via this route. Current
guidelines stipulate that 250 μg should be given intra-
Oxytocin administration
muscularly, repeated every 15 min to a maximum of
The administration of oxytocin is associated eight doses, as the last resort. In preeclampsia, the
with significant maternal, fetal, and neonatal adverse best second-line agent is misoprostol, since ergot
events. Maternal arrhythmias, hypotension, uterine alkaloids are contraindicated, and prostaglandin F2ά
hyperstimulation and hyponatremia, fetal decreases may be hazardous.
in oxygen saturation (SaO2) related to contraction
Cricoid pressure to prevent regurgitation
frequency, and neonatal seizures, hyperbilirubinemia,
or retinal hemorrhage have been reported following Standard practice for patients undergoing ce-
oxytocin use. In an effort to improve patient safety, sarean delivery under general anesthesia is rapid se-
practitioners have questioned the high-dose, non- quence induction (RSI) with cricoid pressure, by which
standardized oxytocin practices currently in use. In passively regurgitated gastric contents are prevented
non-laboring women undergoing cesarean delivery, from entering the pharynx and trachea. The ability
a ‘ceiling effect’ of oxytocin 5 IU is witnessed, beyond of the manoeuvre to prevent regurgitation has been
which no further improvement in uterine tone and blood demonstrated in cadavers, but its efficacy in saving
loss is observed; in laboring women, high doses of oxy- life is difficult to establish. The mechanism allowing
tocin did not obviate the need for additional uterotonic aspiration of gastric contents is a four-stage process:
agents. Interestingly, a small loading dose of oxytocin
(ED 90 = 0.35 IU) has been determined to be sufficient 1. A full stomach, either from eating or from delayed
in producing adequate uterine contractions during gastric emptying, due to stress or systemic opioid
elective cesarean deliveries in non-laboring women; a administration.
similarly low loading dose (ED 90 = 2.99 IU) is required 2. Reflux, a known problem in late pregnancy.
in laboring women.
3. Regurgitation of esophageal contents into the
Current recommendations for uterotonics in estab-
pharynx, once the upper oesophageal sphincter
lished uterine atony
relaxes during induction of anesthesia.
The British National Formulary (BNF), the
4. Aspiration, which can occur with loss of laryngeal
American College of Obstetricians and Gynecologists
reflexes and before the airway is secured by a
(ACOG), and the Society of Obstetricians and Gy-
cuffed tracheal tube.
necologists of Canada (SOGC) provide guidance for
cesarean deliveries accompanied with a postpartum Little can be done about (2), correctly applied
hemorrhage (PPH), indicating that a range from 5 IU cricoid pressure can only prevent (3) and swift and
to 40 IU can be used; further, the SOGC suggests that skilled intubation is designed to cope with (4). Passing
oxytocin 10 IU can be given as an i.v. push in these an oro- or naso-gastric tube preoperatively to empty the
conditions. stomach or induce vomiting before anesthesia could
In view of down-regulation of oxytocin receptors be more effective than cricoid pressure as a means of
following prior exposure to oxytocin, there should be a preventing aspiration of stomach contents. In selected
low threshold for the use of uterotonics with a different cases, the use of RSI may prove a greater risk to the
mechanism of action, such as ergometrine, and pros- patient (severe cardiomyopathy, incipient rupturing an-
taglandins F2 ά and E1, in cases of established uterine eurysm) than a slowly titrated induction with or without
atony. cricoid pressure.

Wedge to prevent aortocaval compression siderably, but a minority of women may have particular
susceptibility even at these levels. Calvache JA et al.
Maternal cardiovascular compromise and fetal
2011 established that the use of right lumbar–pelvic
distress in supine position and their relief in full lateral
wedge was not effective in reducing the incidence of
position are well recognized. The systematic use of
hypotension during spinal anesthesia for cesarean sec-
lateral table tilt or pelvic tilt to reduce supine aortocaval
tion. Patients in whom the wedge was used had higher
compression during CS was developed in 1972 by
systolic blood pressure values during the first 5min of
Crawford and is now ingrained in obstetric anesthetic
anesthesia and fewer episodes of nausea. The risk of
practice. Crawford designed a wedge shaped cushion
hypotension remains substantial.
upper surface of which was arbitrarily angled at 15º.
Other potentially less precise means are, air filled 3 litre Post-spinal hypotension: fluids or vasopressors?
fluid bags or rolled sheets and lateral tilt of the whole
Maternal hypotension following spinal anesthesia
operating table. There is a strong suggestive evidence
may impair uteroplacental perfusion evidenced by
that lateral tilt as used in routine practice, does not
decreased umbilical arterial pH values among infants
relieve aortocaval compression completely. There are
born to mothers who received spinal versus general or
also reports of severe maternal cardiovascular collapse
epidural anesthesia. To maintain hemodynamic stabil-
during CS in women who were apparently adequately
ity, fluid loading is advocated as one of the strategies
tilted. There is also variability in the susceptibility to
following spinal anesthesia. Colloids or crystalloids,
aortocaval compression. An increase in heart rate
both have been administered as a preload (before
indicates reduced venous return from superior vena
spinal anesthesia) or as a coload (started as the
cava compression and this effect persists in spite of
spinal anesthetic is dosed and continued while it is
‘standard’ pelvic tilt. The lateral position was associ-
developing), but there is no effect on the subsequent
ated with less hypotensive episodes and less use of
incidence of maternal hypotension or the requirement
ephedrine than the 12degree tilt position. No significant
of vasopressors to manage post spinal hypotension. It
difference in cardiac output between patients placed
has been further found that regardless of fluid compo-
supine or with measured left or right lateral tilt of 5º and
sition or timing of the fluid, approximately 60% of the
12.50 was found, although mean values were lowest in
elective CS patients require vasopressors to maintain
the supine and right tilt positions. This is an important
hemodynamic stability.
finding as it could make anesthesiologists discount
inadequate tilt as a cause of hypotension or collapse Among the two vasopressors frequently pre-
in a pregnant woman. ferred in the obstetric patients, evidence proves that
ephedrine crosses the placenta to a greater extent and
Fetal effects of maternal position follow the trend
undergoes less early metabolism and redistribution
found in maternal cardiovascular effects such that
than phenylephrine (a direct alpha-adrenergic agonist)
lesser degrees of tilt are comparable to supine whereas
causing direct fetal metabolic acidosis which has made
large tilt angles are similar to lateral position. There was
ephedrine less desirable as a first-line treatment. The
no difference in fetal heart rate patterns after regional
proposed mechanism is that direct fetal beta-adrenergic
analgesia in women managed supine with measured
stimulation increases anaerobic glycolysis and causes
300 lateral tilt compared to those who laboured in the
a hyper metabolic state.
lateral position. However, significant fetal problems,
may develop in a small minority of women who have Phenylephrine has emerged as the favored va-
persisting severe aortic compression with this amount sopressor to prevent and treat maternal hypotension
of tilt, that will be relieved on turning to the full lateral following spinal anesthesia. It has been proved to be
position. Thus, to summarize inferior vena caval com- more effective and faster in restoring baseline MAP,
pression is demonstrable upto 12.5 - 150 of lateral tilt reduced maternal cardiac output and heart rate back
and aortic compression upto 300. The use of 150 of tilt towards baseline values when compared to ephed-
at CS and 300 during labour reduces the effects con- rine, which further increases both the heart rate and

cardiac output. However, when using phenylephrine, delivery under general anesthesia. Recently intrave-
if the heart rate decreases below baseline, then car- nous infusions of MgSO4, have been used along with
diac output is likely to be reduced as well, so further anesthetic induction to evaluate its effects on intraop-
doses of phenylephrine should be withheld, reduced erative awareness.. BIS scores have been found to be
or replaced with ephedrine. Another advantage of us- significantly reduced with infusion rates of 45mg/kg (as
ing phenylephrine, if co-administered with oxytocin, is bolus) followed by 15mg/kg/h.
that it halves the usual 50% drop in systemic vascular
Antenatal MgSO4 has also been found to reduce
resistance following oxytocin, thus providing greater
the risk of cerebral palsy for infants born before 34
maternal hemodynamic stability, and allowing more
weeks of gestation as also improving neurological
generous oxytocin dosing.
outcome at discharge for term neonates with severe
ED95 of intrathecal dose of bupivacaine in obese perinatal asphyxia, who received 250mg/kg of Mg
parturients for LSCS within 6hrs of birth followed by three doses repeated
every 24 hrs. The role of magnesium in providing
Obesity is a problem that obstetric anesthesi-
cerebral protection is likely to be due to its likely role
ologists are encountering with increasing frequency.
in relieving oxidative stress and excitotoxicity due to
Whether obese parturients who undergo spinal anes-
excessive glutamate stimulation of preoligodendrocytes
thesia for cesarean section (CS) require more, less,
in the periventricular white matter through several
or the same dose of local anesthetic as non obese
mechanisms.
parturients is an important question to be answered.
Many investigators feel that morbidly obese parturients Transfusion strategy in obstetric hemorrhage
(women with a body mass index >40) require lower
Most transfusion strategy protocols recommend
doses of intrathecal local anesthetics than nonobese
early administration of clotting factors in an effort to
women. Carvalho et al, 2011, concluded that morbidly
avoid the “bloody vicious cycle” of acidosis, hypo-
obese and nonobese parturients do not respond differ-
thermia and coagulopathy, as treatment of hemorrhage
ently to modest bolus doses of intrathecal bupivacaine.
with only RBC transfusion worsens the coagulopathy
They also recommended that doses < 10 mg not be
by diluting coagulation factors and platelets. Recently,
used for a single-shot spinal technique in obese women
there has been a trend towards giving more clotting
and the bupivacaine dose not be reduced in this popu-
products earlier, mimicking the whole blood strategy
lation. They emphasized that doses of >15mg should
used by the armed forces. It has been suggested that
not be used in obese women as the mathematically
increasing the ratio of clotting products to packed red
extrapolated value for ED95 had not been evaluated for
cells, to a ratio of 1:2 or even 1:1, might be one method
safety. The authors also suggested that obese women
of preventing coagulopathy. The risk of DIC can be
may be best suited to a combined spinal-epidural,
reduced by avoiding the precipitant factors such as
epidural, or continuous spinal technique since they
shock, hypothermia and acidosis.
seem to have a more variable response to intrathecal
dosing. Another important finding of the study was that Suggested reading
adequate initial sensory levels obtained with low doses 1. Carvalho,B; Collins, J; Drover, DR; Atkinson Ralls L.
of bupivacaine do not guarantee adequate anesthesia and Riley ET. ED(50) and ED(95) of Intrathecal Bupiva-
throughout surgery There is still no evidence-based caine in Morbidly Obese Patients Undergoing Cesarean
reason to lower anesthetic dose for single-shot spinal Delivery. Anesthesiology. 2011;114(3):529–35
anesthesia for CS solely on the basis of body mass
2. Gupta S. Controversies in obstetric anesthesia. Ind J
index.
Anaesth.2005;49(3):180-89.
New role of MgSO4 in LSCS
3. Anim-Somuah M, Smyth RMD, Howell CJ. Epidural
Obstetric procedures are known to carry a high versus non-epidural or no analgesia in labour. Co-
risk of maternal awareness especially during caesarean chrane Database of Systematic Reviews 2005, Issue

4. Copyright © 2010 The Cochrane Collaboration. 6. Toledo P. What is new in obstetric anesthesia? The
Published by JohnWiley & Sons, Ltd. 2011 Gerard W Ostheimer lecture. Anaesth. An-
alg.2011; 113(6):1450-58.
4. Calvache,JA; Munõz,MF; Baron, FJ. Hemodynamic
effects of a right lumbar–pelvic wedge during spinal 7. Bacterial meningitis after intrapartum spinal anesthesia-
anesthesia for cesarean section International Journal NY and Ohio,2008-2009. MMWR Morb Mortal Wkly
of Obstetric Anesthesia (2011) 20, 307–311 Rep 2010;59:65-9.
5. Mhyre JM. What’s new in obstetric anesthesia? Inter- 8. Loubert C, Hinova A, Fernando R. Update on modern
national J Obs Anaesth. 2011;20:149-159. neuraxial analgesia in labour: a review of literature of
last 5 years. Anesthesia 2011; 66:191-212.

Anesthesia for Bariatric Surgery 77 Rajeshwari
01 ANESTHESIA FOR BARIATRIC SURGERY
Rajeshwari
It is a well known fact that the incidence of obesity hypertrophy diminishes, producing systolic dysfunction
is on the increase. European figures are at 15-20%; (obesity cardiomyopathy). Reduced LV compliance
in the US, more than 30% adults and nearly 20% in the face of volume overload leads to increased
children between ages 2-19 years are obese; while in LVEDP and pulmonary edema ( diastolic dysfunction,
India, thanks to poverty, the figures are around 10% failure).
in the general population. However, obesity in the
Morbidly obese have very limited mobility and may
‘upper middle class’ is nearly 30% for men and 50%
appear asymptomatic even in the presence of signifi-
for women! Ideal body weight (IBW) is defined as the
cant cardiac disease. They may be sleeping upright
weight for a particular height associated with the lowest
and may deny any history of orthopnea or paroxysmal
mortality rate. It is calculated (in kg) as height (in cm)
nocturnal dyspnea. Reduced exercise tolerance is
-100 for males and height (in cm) – 105 for females.
manifest even if the patient is simply asked to walk
The body mass index (BMI) is the standard for defining
the length of the ward; assuming the supine position
extent of excess weight and is calculated as kg/ (height
results in orthopnea and even cardiac arrest.
in cm) 2. BMI of 20-25 is normal; 26-30, overweight;
above 30, obese; >35, morbidly obese (MO); and > Hypertension
55, super morbidly obese. Obese individuals have an HT is mild to moderate in the majority (50-60%)
increased incidence of cardiovascular disease, arthri- of patients and severe in 5-10%. Hyperinsulinemia,
tis, diabetes and malignancy. Bariatric or weight-loss a frequent finding, aggravates HT by sympathetic
surgery is presently a treatment option for the morbidly stimulation and sodium retention. Insulin resistance
obese, and the results are spectacular in the majority increases the pressor activity of norepinephrine and
of patients. angiotensin 2. OSA (see below) contributes to HT due
Pathophysiology of obesity to the repetitive increase in sympathetic tone associ-
ated with arousal. LVH is found in nearly 20% patients
Changes in organ systems consequent to obesity
with OSA.
which have significant anesthetic implications include
the cardiovascular, the respiratory system and the air- Respiratory system
way. Obstructive sleep apnea (OSA) occurs as a sequel Obese individuals need to increase their minute
to altered airway anatomy, and obesity hypoventilation ventilation (MV) to meet the increased oxygen require-
syndrome (OHS) is seen in obese individuals with ment at rest. They have increased work and energy
chronic pulmonary disease. cost of breathing. Significant reductions are seen in
Cardiovascular system (CVS) FRC, VC and TLC due to increase in chest wall and
intra abdominal fat. These reductions occur expo-
Changes in the CVS dominate the causes of mor-
nentially with increasing BMI. Reduced FRC leads to
bidity and mortality in morbid obesity. They manifest
airway closure during tidal ventilation, resulting in V/Q
as hypertension (HT), ischemic heart disease (IHD)
mismatch, shunt and hypoxemia. Induction of anesthe-
and cardiac failure. Increase in blood volume leads to
sia reduces FRC further; obese individuals therefore
increased cardiac output. This initially leads to stretch-
tolerate apnea very poorly and desaturate rapidly. This
ing and increased wall stress of the left ventricle (LV),
fact has led to various technical modifications during
producing eccentric hypertrophy. LVH also occurs due
induction including the use of ‘ramped’ position (see
to HT. Gradually the capacity of the overfilled LV to
below).

Obstructive sleep apnea (OSA) block and ventricular dysrhythmia. These may account
for nocturnal angina/MI observed in these patients.
OSA is characterized by heavy snoring interrupted
Hypoxemia, hypoxic pulmonary vasoconstriction and
by periods of apnea and arousal. It is defined as the
increased intrathoracic pressures lead to the develop-
occurrence of episodes of cessation of airflow lasting
ment of pulmonary arterial hypertension (PAH). This
more than 10 seconds during sleep (more than 5 per
accounts for 70% of RVH seen in OSA. Chronic OSA
hour). Hypopnea (defined as hypoventilation with fall
is associated with hypoxemia, hypercapnia, PAH and
of SpO2 by > 4%) also is part of the symptom complex.
cardiac dysrhythmias. These patients are frequently
Severity of OSA is traditionally classified by the apnea-
dependent on hypoxic drive for normal breathing.
hypopnea index (AHI) graded during polysomnography
(PSG): mild, 5-15; moderate, 15-30; and severe, >30. However, many MO patients may not be aware
OSA is present in nearly 50-70% of morbidly obese that they snore, and observer reliability of apnea may
patients. be misleading. Although PSG is the gold standard for
diagnosing and quantifying OSA, it may not be practical
There is an inverse relationship between obesity
or feasible for all patients. Brodsky (2011) recommends
and pharyngeal wall thickness. Relaxation of the upper
that all MO patients should be presumed to have OSA
airway muscles during sleepÆ collapse of soft-walled
and managed accordingly. Clinical scoring systems
pharynx between uvula and epiglottis. Excess fat in
(STOP-BANG, Berlin questionnaire) may be used
the pharynx narrows the pharynx and also changes
as alternatives for diagnosis in the absence of PSG.
its shape. The upper airway is also compressed by
However these cannot quantify severity of OSA.
external fat; neck circumference is seen to correlate
well with severity of snoring. OSA disturbs normal sleep OSA patients are extremely sensitive to opioids
due to ventilatory effort-induced arousal and causes and have airway problems at induction and extubation.
deprivation of deep, restorative sleep. This results It is important to make a definitive diagnosis so as to
in daytime sleepiness, headaches, fatigue, nocturnal plan pre operative CPAP, analgesia, extubation and
enuresis, personality changes, decreased cognitive post operative care.
and intellectual function and behavioral changes.
OSA is also an independent risk factor for the
OSA is the major concern for anesthesiologists metabolic syndrome.
involved in bariatric (and other procedures in MO)
Patients diagnosed to have moderate or severe OSA
due to the effects produced on the cardiopulmonary
should undergo a period of CPAP therapy prior to
system. During sleep, repeated falls in PaO2 result
elective surgery. CPAP produces results as below:
in bradycardia, long sinus pauses, 20 degree heart
Duration of CPAP Effect

2 weeks Corrects abnormal ventilatory drive
3 weeks Increases LVEF in CHF
4 weeks Reduced BP, HR, 35% increase in EF
4-6 weeks Reduced tongue volume and increased pharyngeal space
8 weeks Reduction in CV risk, morning HT
3-6 months Reduction in PAH
OSA patients receiving preoperative CPAP have dyspnea, respiratory symptoms, cardiac symptoms,
been reported to have fewer perioperative complica- exercise tolerance). Scoring systems like STOP BANG
tions than their untreated counterparts. can be used to screen for OSA (Snoring, Tiredness,
Observed apnea, blood Pressure, BMI, Age, Neck
Pre operative evaluation: Clinical
circumference, Gender). BMI, blood pressure should
This will include relevant history (snoring, OSA, be documented.
diabetes, previous anesthetics, h/o difficult intubation,

Airway examination: there is a wide discrepancy in

the reported incidence of difficult intubation (DI). Ju-
vin (2003) and Shiga (2005) reported an incidence of
about 16% in patients with BMI >35. However Brodsky
reported the incidence as 3%. This difference has
been attributed to improved positioning in the latter
series. Standard clinical tests are not useful to predict
with absolute certainty the probability of DI. Juvin et
al stated that Modified Mallampati Score (MMPS) III/
IV had low specificity and sensitivity and poor predic-
tive value. Brodsky stated that a neck circumference
of 40 cm was associated with a 5% probability of DI,
and 60 cm with a probability of 35%. Wu correlated a
large thyromental distance and caudad displacement
of the hyoid (seen on lateral neck x-ray) with difficult
laryngoscopy necessitating videolaryngoscopy. There
is, however, a strong correlation between DI and OSA.
Further, obesity is a factor in 37% injury claims related
to airway management at induction of anesthesia. OSA,
a short, thick neck and DI are related to each other.
More recently, MMP score >3 and male gender have
been seen to correlate with DI; BMI, OSA and neck
circumference did not.
It is prudent to make a thorough airway exami-
nation and make all relevant measurements (Fig 1), Laboratory and radiology
and also obtain a lateral view of the neck to see the
Complete blood count, serum biochemistry are
position of the hyoid and amount of pre tracheal soft
carried out; optimization of blood sugar values; x-ray
tissue. The decision of awake intubation should be an
chest, neck, ECG, long lead II, Echocardiogram form
individualized one, based on the extent of anticipated
the other investigations. For chronic obesity and OSA
difficulty and the skill of the operator.
arterial blood gas analysis, room air SpO2 are required
Fig 1 to plan intra and post operative management.
Induction and maintenance of anesthesia
The operating room needs to be specially pre-
pared for bariatric procedures. An appropriate table
capable of bearing 400lbs, with arm extensions and foot
support, should be available. Personnel in adequate
numbers and a transferring blanket should be ready.
DVT prophylaxis stockings and pump and adequate
padding material will be added perquisites.
The large chest and trunk tower over the head if
the obese patient is put in the supine or in the ‘sniff-
ing’ position used for standard laryngoscopy (Fig 2). If
the head and shoulders are supported by appropriate

pads and pillows the tragus and sternal angle can be

brought on a nearly level plane. This position, known
as ‘ramping’, has several advantages:
1. Improves laryngoscopic view
2. The gradient for passive regurgitation is re-
duced
3. The ‘safe apnea’ time is increased.
In addition, 25-300 reverse Trendelenburg tilt
and manual PEEP of 10 cm H2O, or NIPPV during pre
oxygenation achieve similar results. Pre oxygenation
is vital and should be performed with 10 l/min oxygen Fig.2
flow with PEEP or NIPPV as mentioned above.
Rapid sequence induction may be individualized
rather than routine. Actual incidence of clinically sig-
nificant aspiration has not been demonstrated.
Multiple options for securing the airway should
be available. It is a good idea to have an extra person
experienced in managing difficult airway especially in
the presence of significant co morbidities like OSA and
IHD. Occasionally mask ventilation is extremely difficult
and may require two-person mask ventilation (Fig 3).
The ILMA or Proseal offer good intermediate choices
for difficult mask ventilation. The added advantage of
the ILMA is that it allows ventilation during attempts at
intubation.
Managing the airway in the morbidly obese is a After tracheal intubation an oro-gastric drainage
daunting undertaking since CICV situation cannot be tube is placed in the stomach.
predicted by usual clinical methods. In case of any Drug choices and dosing
doubt it is safest to proceed with awake intubation after
Propofol is the agent of choice for induction. Both
thorough airway topicalization.
propofol and thiopentone are given according to LBW
Fig.2 (ideal body weight+ 20% of IBW). Propofol infusion
is based on a ‘corrected’ weight (IBW +40% excess
weight), Suxamethonium is given as 1 mg/kg TBW.
Plasma cholinesterase levels increase with TBW. The
non-depolarizing relaxants are administered according
to IBW; TBW dosing delays recovery. Similarly, fen-
tanyl, alfentanil, sufentanil and remifentanil are given
according to LBW, as TBW dosing leads to overdosage.
Antibiotics are dosed based on LBW.
Maintenance
The low blood-gas solubility of desflurane fa-
cilitates speed of emergence and re-establishment of

reflexes. Clinical significance of more rapid emergence BIS and entropy monitoring are frequently used to ac-
is not very clear. Studies comparing desflurane, sevo- curately titrate depth of anesthesia, given the difficulties
flurane and propofol infusion have failed to find signifi- in deciding correct doses in these patients.
cant differences between techniques. A small series
Monitoring of the neuromuscular junction is use-
on obese patients undergoing minor peripheral surgery
ful in precise titration of muscle relaxant. Inadequate
found lesser disturbance of pulmonary function at 24
relaxation reduces pneumoperitoneal space, ‘grips’ the
hours with desflurane compared to propofol infusion.
long bariatric instruments, and makes intra-abdominal
Clonidine (pre-operative and morning of surgery) manipulation difficult. Equally, it is important to ensure
and dexmedetomidine (0.2μg/kg/min) are gaining popu- that the effect of relaxant is on the wane by the end of
larity due to their opioid-sparing action. Dexmedetomi- surgery, so that tracheal extubation is safe.
dine may cause hypotension and require treatment.
In patients with poor peripheral venous access,
Intra operative oxygenation insertion of a central venous catheter (CVC) is a good
option. Use of ultrasound helps to locate and cannulate
VC and alveolar recruitment maneuvers result in
the internal jugular/ subclavian without arterial or other
improved intra operative oxygenation, less atelectasis,
injury.
shorter PACU stay and less respiratory complica-
tions. The recruitment maneuver consists of providing Extubation and post operative care
escalating levels of PEEP in 5 cm increments up to a
Airway difficulties at extubation tend to be under-
maximum airway pressure of 40-42 cm H2O, continue
appreciated. Nearly 70% airway claims have been
for 10 breaths and reduce PEEP back to basal levels.
related to extubation. Careful attention should therefore
Recruitment can cause hypotension due to high intra
be paid to emergence. It is advisable to achieve the
thoracic pressures, especially in conjunction with the
same position as was maintained during intubation,
steep reverse Trendelenburg positions used during
along with equipment for airway rescue. The patient
bariatric surgery.
should be fully awake, demonstrate adequate muscle
Intra abdominal pressure should be limited to strength and follow oral commands. Adequate tidal
≤15 cm H2O. Pressures ≥ 20 cm H2O result in caval volumes should be generated and airway reflexes brisk.
compression and reduction in cardiac output. Residual neuromuscular blockade should be reversed.
The patient is maintained in a semi-upright position. A
The gastric bougie
recruitment maneuver at this stage is useful in short-
Atraumatic insertion of the wide bougie and its term improvement of oxygenation.
careful manipulation are necessary to guide the sur-
Immediate NIPPV after extubation may be more
geon in gastric stapling. The orogastric tube is removed
beneficial than after arrival in the ICU.
before inserting the bougie. Since the table is nearly
vertical during this maneuver, the anesthesiologist has Many patients want to assume the lateral decubi-
to stand on a footrest and support the endotracheal tus position after extubation. Lateral decubitus position,
tube while inserting and retracting the bougie. combined with upper body elevation, improves mainte-
nance of, and increases pharyngeal airway diameter.
Monitoring
It is important to resume CPAP if the patient
Standard monitoring protocols (ECG, NIBP, SpO2)
was using it pre operatively. CPAP reduces risk of
are followed. Special consideration should be given to
re-intubation, ICU stay, pneumonia and sepsis. CPAP
co morbidities. NIBP monitoring is a challenge. The
does not increase surgical complications (anastomotic
massive conical upper arms lead the cuff to slip off. A
leak), but improves oxygenation.
low threshold for invasive BP monitoring is encouraged.
Not only are accurate BP readings obtained, in addition, In patients with severe OSA it may be advisable
ABG sampling can be performed in the post operative to electively extubate the trachea in the PACU after
period to monitor patients with OHS and OSA.
a few hours or even overnight, which would permit with local anesthetic forms the mainstay. Thoracic
administration of analgesia without fear of respiratory epidural analgesia is recommended for open bariatric
depression and loss of airway. surgery.
Analgesic management Outpatient bariatric surgery
In this patient subgroup with altered respiratory Although series of laparoscopic gastric banding
mechanics, tendency towards arterial hypoxemia and (LGB) as outpatients has been reported, nearly 35%
CO2 retention, IV boluses or infusions of narcotics patients required overnight admission. There are cur-
are not recommended or used. Multimodal analgesia rently no recommendations to perform bariatric surgery
with NSAIDs along with generous port site infiltration on outpatient basis.

Anesthesia for Kidney Transplant 83 Meenakshisundaram A L
01 ANESTHESIA FOR KIDNEY TRANSPLANT
Professor Meenakshisundaram A L
Thanjavur Medical College
Thanjavur
Introduction Allocation and timing

Kidney transplant is indicated for patients with Allocation of grafts is based on both matching of
ESRD caused by glomerular disease, diabetes mel- the grafts to recipients and a waiting list system, with
litus, hypertensive kidney disease, polycystic kidney special priority given to children to minimize the impact
disease and tubulo interstitial disease of CRF on growth.
Matching Timing of the transplant is important as future
Matching of the organ to recipient can be divided graft function is directly related to warm ischemic
into three phases: time (harvest and transplant time), cold ischemic time
(storage time, especially if greater than 24 hours),
Blood type matching
transplanted graft perfusion and pre-donation graft
Using the four major blood types A, B, AB and O state. Living donation is a scheduled event and allows
as with blood transfusion. optimal preparation of the donor and recipient alongside
Tissue matching minimizing organ preservation time.
This relates to genetic matching between donors Pathophysiologic manifestations of CRF

and recipients. Currently six specific antigens called Hypervolemia
major histo-compatibility complex, are defined in
each donor and recipient. The best compatibility is a Total body contents of Na and water are increased
six-antigen match between donor and recipient. This in CRF which may manifest as increase in weight gain.
match occurs 25 percent of the time between siblings This can be masked by decrease in lean body mass.
and occasionally at random in the general population. Diuretic resistance to loop diuretics can be overcome
Long term outcomes relate to matching, with six antigen by combining it with metolazone, which acts by inhibit-
match having best outcome, then 5 antigen match and ing the Na-Cl Co transporter of the distal convoluted
so on. However, immunosuppressant medications have tubule.
improved to the extent that even poor tissue matches
Acidemia
now appear to respond and survive similarly.
The patients with CRF have reduced ability to
Crossmatching
produce ammonia. The CRF patients have non anion
Very sensitive and final test performed on a kidney gap acidosis initially which progresses to large anion
donor and recipient. The technique allows definition of gap acidosis as the disease advances with recipro-
how a transplant recipient may respond to particular cal decrease in plasma HCO3.The acidemia could be
cells or proteins of the donor kidney. This has allowed corrected by hemodialysis. The patient with chronic
for possible detection of a recipient who would reject metabolic acidosis with partial respiratory compensa-
an organ. A negative crossmatch means the recipient tion (hypocapnia) can develop established acidosis
has not responded to the donor and the transplant can on normocarbia because of standard mechanical
go ahead. A positive cross match means the recipi- ventilation in the periop period. For these patients if
ent has responded to the donor and the transplanted
opioids are given in the post operative period for pain
kidney is likely to be rejected. Recent advances have
relief it can further increase CO2 and increase acidosis.
seen progress in successful transplantation across a
Worse still this acidosis can aggravate pre existing
positive crossmatch.
hyperkalemia in CRF.

Hyperkalemia matocrit . Further, it avoids RBC transfusion, reduces

the requirement for hospitalization and decreases
Potassium excretion in GIT is augmented in CRF.
cardiovascular mortality by about 30%.
Hyperkalemia can occur in protein catabolism, hemoly-
sis, hemorrhage, transfusion of stored RBCs, metabolic Clotting defects manifested by prolongation of
acidosis and exposure to drugs that inhibit potassium bleeding time due to decreased activity of platelet factor
entry into cells or secretion in distal nephrons. 3, abnormal platelet aggregation and adhesiveness and
impaired prothrombin consumption. The platelet factor
Cardiac manifestations
abnormality can be corrected by dialysis but bleeding
Cardiovascular manifestations are the predomi- time can even be prolonged in dialyzed patients,which
nant cause of death in patients with ESRD. Acute can be managed by desmopressin, cryoprecipitate,
myocardial infarction, cardiac arrest of unknown etiol- conjugated estrogens, blood transfusions and eryth-
ogy, cardiac arrhythmia and cardiomyopathy account ropoietin.
for greater than 50% of deaths in patients on dialysis.
Central Nervous system
Hypertension is a common complication of CRF which
may be due to hypervolemia (responds to diuretics) or Drowsiness, memory loss, myoclonus, stupor and
hyperreninemia (not responding to diuretics) or altera- coma can occur in ESRD. Peripheral and autonomic
tions in blood levels of vasoactive substances result- neuropathy can coexist in CRF.
ing in local and systemic changes in vascular tone.
GI tract
LVH and dilated cardiomyopathy occurs in response
to increase in intravascular volume and after load. Uremia causes delayed gastric emptying and
Accelerated atherosclerosis is due to disordered fat hence all patients posted for surgery should be consid-
and glucose metabolism, pericarditis can also occur ered to have full stomach irrespective of the period of
in CRF. The accumulation of uremic toxins reduce starvation. Gastric volume greater than 0.4ml/kg were
myocardial performance. found in 50% of diabetic uremic patients and hence
rapid sequence induction to be considered in diabetic
Pulmonary manifestations
uremic patients when compared to non diabetics.
Unique “low pressure” pulmonary edema can oc-
Immunological
cur in CRF due to increased permeability of alveolar
capillary membranes with normal or mildly elevated Immunosuppression is prevalent in ESRD and
intra cardiac and pulmonary capillary wedge pressure. hence incidence of infection is increased. Antibiotics
Radiologically it will have a “butterfly wing” distribution and barrier nursing are to be practiced in ESRD and
of peripheral vascular congestion. It could be managed during renal transplant immunosuppressive drugs are
by dialysis. needed.
Hematologic manifestations Effect of drugs in CRF
CRF causes normochromic, normocytic anemia Opioids: Morphine metabolism and elimination is
and would be noticed when GFR is decreased to 30ml/ very much prolonged and it may lead to respiratory
minute. It is due to decreased erythropoietin produc- depression. It is not preferable in CRF. Pethidine and
tion or iron deficiency. Iron deficiency may be related nor pethidine are excreted by kidney and hence they
to blood loss from repeated laboratory testing, blood are also not preferable in CRF as CNS toxicity due to
retention in the dialyzer or GI bleed. norpethidine is very much prolonged.
Anemia (normochromic normocytic ) requires Fentanyl and remifentanil pharmacodynamics and

treatment with iron, darbopoietin alfa and human pharmacokinetics are not altered by CRF. Alfentanil
recombinant erythropoietin which can restore the he- and sufentanil may have exaggerated effects but delay
in recovery usually does not occur.

Inhaled anesthetics of rocuronium is increased in renal failure because of

increase in the volume of distribution with no change
Because of reductions in renal blood flow, loss
in clearance.
of renal autoregulation, neurohumoral and neuroen-
docrine responses the inhaled anesthetics reversibly Reversal Agents
depress renal function, GFR, renal blood flow and urine
Excretion of all the cholinesterase inhibitors (Neo-
output.
stigmine, Pyridistigmine and edrophonium) is delayed
All modern inhalational agents are suitable in CRF in CRF more than the elimination of muscle relaxants.
as the elimination is by the lungs. The safety of desflu- So, if recurarization occurs, it may be due to some other
rane and sevoflurane usage in CRF is confirmed. cause, such as an interaction of the residual muscle
relaxant with an antibiotic or a diuretic. It would be bet-
Intra venous anesthetics
ter if the use of relaxants and reversal agents is done
Thiopentone: Highly protein bound and is a weak acid. with the help of a nerve stimulator in CRF.
In CRF, the albumin concentration would be reduced
Antihypertensives
and as such increased free fraction of thiopentone
exerts greater effect. As it is a weak acid, in acidosis More than 90% of thiazides and 70% of frusemide
due to CRF the unionized fraction would be more and are excreted by the kidneys and have prolonged dura-
hence more effect. (28% free fraction in CRF compared tion of action in CRF. Propranalol (liver metabolism),
to 15% normal). esmolol (biodegraded by esterases in the cytosol of
RBCs) are not affected by CRF. Calcium channel block-
Propofol: Does not affect renal function and hence
ers (liver metabolism) and nitroglycerin (less than 1%
preferred in CRF. Prolonged infusion of propofol in
unchanged excretion in urine) are also safe. Sodium ni-
CRF produces green urine because of the presence
troprusside is less safe because of thiocyanate toxicity
of phenols in the urine.
as it is excreted in urine and even normally the half life
Benzodiazepines exert profound effect (diaz- of thiocyanate is more than 4 days. The elimination half
epam). As inhaled anesthetics depend on pulmonary life of hydralazine is prolonged in uremic patients.
excretion, inhalation induction has definitely an edge
Vasopressors
over intravenous induction in uremia (CRF).
Alpha adrenergic stimulator phenylephrine would
Muscle relaxants
be effective but cause interference in renal circulation.
Succinylcholine is safe if the patient has under- It would be better to try volume expansion during hy-
gone dialysis within 24 hours preoperatively. It should potension in CRF than drug therapy and if drug therapy
be used only if the serum potassium is within normal is needed β- adrenergic agonists (increase myocardial
limits otherwise hyperkalemia induced by the drug may irritability) or dopamine should be used.
be dangerous.
Preoperative assessment
Atracurium and vecuronium are safe but the dura-
Pre operative assessment should concentrate on
tion of action of vecuronium is prolonged in CRF (half
renal function and also about the coexisting diseases.
life of 83 minutes vs 52 minutes) as 30 % vecuronium
The intravascular volume should be optimal before in-
is eliminated by the kidneys. Atracurium is safer as it
duction which can be estimated by comparing patient’s
is metabolized by Hoffman elimination (pH dependant
weight with their “dry weight”, which hemodialysis pa-
enzyme independent elimination). Cis atracurium which
tients usually know. Patients undergoing hemodialysis
is cis isomer of atracurium is also safe.
may have fluid removed just before surgery for optimal
The action of short acting drug mivacurium fluid management. But these patients can develop
(metabolized by plasma pseudocholinesterase) is hypotension during induction due to hypovolemia.
prolonged by 10 to 15 minutes due to decrease in Hypokalemia and residual anticoagulation are other
plasma cholinesterase activity.The elimination half life problems of recent hemodialysis. Electrolyte concentra-
tions particularly potassium and HCO3 concentrations predictable depth of anesthesia. No difference was
are to be measured. Potassium should be kept below found in a study comparing balanced anesthesia with
6 meq/liter before surgery. opioid and inhalation agents with TIVA using propofol
and opioids.
Preop cardiac assessment by way of ECG and
stress test for young, non diabetic or stress echocar- Normal saline or Ringer lactate can be used but
diogram with cardiac catheter for long standing disease some studies made out higher rates of severe hyper-
and diabetic patients. Non invasive screening tests to kalemia and metabolic acidosis in the Ringer lactate
analyze CAD in ESRD are performed preoperatively group.
even though there is no evidence based consensus on
ESRD patients are to be considered as full stom-
this score.
ach patients especially with diabetes and hence acid
Perioperative beta blockade provide significant aspiration prophylaxis and/or rapid sequence induction
risk protection from major cardiac events in high risk is to be considered. Stress response to laryngoscopy
patients but some studies have questioned the safety and intubation are to be minimized as pre existing
of these drugs especially in diabetes. hypertension may precipitate myocardial ischemia.
Esmolol and fentanyl/remifentanil are preferred in this
Diabetic patients have higher incidence of auto-
regard.
nomic neuropathy manifested by increase in heart rate
and blood pressure than in non diabetic ESRD patients. The use of succinyl choline is not absolutely con-
Type 2 diabetics would have a combination of visceral traindicated in ESRD as hyperkalemia is not a concern
obesity, atherogenic dyslipidemia, hypertension and if serum potassium is below 5 mEq/liter at the time of
insulin resistance. This combination increases the risk induction. Atracurium and cisatracurium are preferred
of CAD. nondepolarizing muscle relaxants
The last intake of oral hypoglycemic drugs is to Desflurane, isoflurane and sevoflurane are pre-
be noted. It should be avoided on the day of surgery ferred inhalation agents. The production of nephro-
to avoid hypoglycemia under anesthesia. Brittle insulin toxic fluoride ions and compound A with sevoflurane
dependent patients with decreased insulin levels can anesthesia has not compromised the renal function in
develop ketosis and intraoperative acidosis. majority of studies.
Coagulation status is to be ascertained by his- Fentanyl, sufentanil, alfentanil and remifentanil
tory of bleeding and by checking coagulation profile. are preferred perioperative analgesics. Morphine and
Grouping and cross matching is to be done although pethidine are avoided.
blood transfusion is seldom necessary.
Hypotension may occur when the iliac vessels are
Premedication addressing both anxiety and the unclamped and it should be avoided as the graft func-
increased incidence of gastric paresis and reflux in tion depends on adequate perfusion. But α-adrenergic
this patient population should be considered. A state vasoconstrictors like phenylephrine should be the last
of immunosuppression is induced immediately after resort as the transplanted organ seems to be more
anesthesia, just prior to the operation. Immunosup- sensitive to sympathomimetics and likely to compro-
pression is continued in the postoperative period also. mise RBF to the transplanted kidney.
Antibiotics are also given before incision.
Urine output after transplant is to be ensured by
Perioperative management checking mechanical impingement of the graft, vessel
or ureter and by irrigating Foley catheter to remove clots
Whilst transplant surgery has been carried out
or tissues. An intraoperative ultrasound may be used to
under regional anesthesia initially, general anesthesia
assess vascular flow and mannitol, loop diuretics and
with paralysis and controlled ventilation is the current
dopamine could be used for renal preservation. Use
method of choice to provide stable hemodynamics and
of dopamine is questioned in several studies.

Mannitol has protective effect on the renal tubu- Frusemide given as a bolus prior to reperfusion, in a
lar cells and is usually administered to donors before varying dose depending on local protocol (40 –250mg)
recovery and to recipients just before unclamping is aimed at inducing diuresis, promoting urine flow in
the arterial blood flow. In this way mannitol prevents the graft and so avoiding oliguria. This can occasionally
ischemic injury and produces osmotic diuresis in the promote massive diuresis resulting in difficult fluid man-
transplanted kidney. It is administered in low dose as agement post operatively. Mannitol as an intravascular
0.25 to 0.5mg/Kg. Loop diuretics increase the urine volume expander and osmotic diuretic is given with
output and preventing oliguria (400ml/day) is a signifi- the aim of promoting renal blood flow. Again given as
cant achievement. a bolus before reperfusion at a dose of 0.25 – 0.5 g/
kg depending on local protocol, prevents reperfusion
Use of dopamine is not substantiated by studies and
injury.
its agonist fenaldopam is under trial.
Postoperative management
Monitoring
The vast majority of patients will be woken up
Standard monitoring as defined by Indian Soci-
and extubated post operatively. After leaving recovery
ety of Anesthesiologists in 2011 at Mumbai, should
they are nursed in high dependency areas. The aim of
be practiced as routine for all transplant surgeries
a warm, well-perfused patient, that was initiated pre-
and special monitoring like CVP, IAP, TEE should be
operatively, continues in the post-operative period.
reserved for select patients with co morbid conditions.
Fluid regimes are often variable, taking into account the
The status of hemodialysis shunts and fistulas should
previous hour’s urine volume and changes in CVP.
be monitored during positioning and intra operatively
to confirm the presence of a thrill and to document In an otherwise stable patient, oliguria should trig-
patency. ger surgical review and consideration of urgent Doppler
imaging of the grafts blood supply.
CVP to be kept between 10-15 mm of Hg to op-
timize cardiac output and renal blood flow. Immediate Analgesia is often provided by an intra-operative
graft function has been associated with blood volume bolus of fentanyl followed postoperatively by regular
greater than 70 mL/Kg and a plasma volume greater paracetamol and fentanyl. Patient Controlled Analgesia
than 45mL/Kg. protocols, if available, are well tolerated in this group.
Due to their potential renal toxicity, non-steroidal anti
Reversal should be monitored with nerve stimu-
inflammatory drugs should be avoided.
lators and urine output is to be monitored even in the
post operative period. REFERENCES
Operative management 1. Collins B, Johnston T. Renal Transplanation: Urology;
Oct 2009
Future graft function is directly influenced by
transplanted graft perfusion. The general aims are to 2. Salifu M, Otah K; Perioperative Management of the
keep the patients warm and well perfused, maintain an patient with chronic renal failure: Jan 2008.
adequate mean arterial pressure and optimizing fluid 3. UK transplant statistics: www.uktransplant.org.uk
status. The optimal CVP at the point of reperfusion
4. Peters T; RENALIFE 2001 Special edition; Vol 17.
has been debated, previously aggressive fluid load-
ing and a CVP >15mmHg had been recommended. 5. Rang, S; West, N; Howard, J; Cousins, J: Anesthesia
Subsequent evidence suggest a CVP of 7-9 mmHg for Chronic Renal Disease and Renal
may offer equally good graft function but have a lower
Transplantation: European Association of Urology and
risk of volume overload. European Board of Urology Update series (2006): 246-
Other drugs are often used intra-operatively to 256
try to improve graft function. Different units have dif- 6. De Gasperi A, Narcisi S, et al. Periopertive fluid man-
ferent protocols and the evidence to support their use agement in kidney transplantation: is volume overload
is not strong. Most commonly used are dopamine, still mandatory for graft function? Transplant Proc 2006;
furosemide and mannitol. 38:807-9
Dopamine given as an infusion from induction, 7. Millers Anesthesia –Seventh Edition
in a low dose infusion (typically 0.5 – 3 mcg/kg/min).

Role of Goal Directed Therapy in High Risk
Non Cardiac Surgery 88 Lakshmi Kumar
01 ROLE OF GOAL DIRECTED THERAPY IN HIGH RISK

NON CARDIAC SURGERY
Amrita Institute of Medical Sciences and Lakshmi Kumar

Research Centre,
Cochin
Introduction: Concept of goal directed therapy Oxygen is the substrate used in mitochondria for
aerobic metabolism, the ratio of oxygen consumed
Recent advances in surgery and postoperative
to oxygen delivered (VO2/DO2) is called the oxygen
care have reduced the morbidity associated with
extraction ratio (OER). The OER increases as the sup-
surgery, however there are certain groups where the
outcomes are poor. Several scoring indexes like the ply of oxygen decreases until a critical value of DO2
ASA, Goldman’s scoring index, POSSUM and Shoe- when anaerobic metabolism begins to occur. In critical
maker’s criteria have attempted to identify the patients illnesses the ability of the tissues to increase the OER
at high risk and introspection to improve the outcomes is limited making anaerobic metabolism more likely. An
in this group by objective measures and hemodynamic inadequate DO2 is suggested by an increase in OER
variables adjustment. reflected by a low SCV02.
However measures to improve the outcomes by Major surgery is associated with a significant
alteration of hemodynamic variables has not come into systemic inflammatory response and this in itself is
acceptance. Goal directed therapy (GDT) describes the associated with an increase in oxygen demand. If a
use of cardiac output and other parameters to guide patient is unable to achieve this due to cardiopulmonary
intravenous and fluid therapy. This module is derived disease, then there will be a degree of tissue dysoxia,
from the initial investigations of Emanuel Rivers et al which in the face of increased metabolic demand can
who applied this GDT to patients presenting in the ER lead to cellular dysfunction and ultimately organ dys-
within 6 hours after the onset of sepsis. He concluded function, failure and death.
from his study on 260 such patients that when in addi- Complications and death following surgery have
tion to the standard care ( maintenance of mean arterial been shown to be associated with reduced DO2 and
pressure > 65 mm Hg, urine output > 0.5 ml/kg/hr, CVP VO2 or a surrogate, the central venous oxygen satu-
> 8-10 mm Hg), the additional variable of SCVO2 > 70 % ration (ScvO2).Reduced perfusion of the gut has also
reduced the mortality from 46.5% to 30.5%.(1) been implicated in post-operative organ dysfunction,
Pearse et al (2) have suggested criteria for the due to disruption of the gut endothelial barrier with
identification of the high risk surgical patients. These leakage of endotoxin into the circulation, activating
‘high-risk’ patients have a poor outcome primarily due multiple inflammatory pathways
to their inability to meet the oxygen transport demands
DO2 is determined by the cardiac output (CO) and
imposed on them by the nature of the surgical response
the arterial content of oxygen.(CaO2). Hence increas-
during the peri-operative period. It has been shown that
ing DO2 is achieved by increasing CO and or CaO2.
by targeting specific hemodynamic and oxygen trans-
As dissolved oxygen is small, CaO2 is increased by
port goals at any point during the perioperative period,
increasing the arterial oxygen saturation and or the
the outcomes of these patients can be improved.
hemoglobin concentration. Therefore the cardiac output
This goal directed therapy includes the use of fluid is the variable that is most readily manipulated in order
loading and inotropes, in order to optimize the preload, to increase DO2, and this is usually performed using
contractility and after load of the heart whilst maintain- fluids and inotropes to improve blood flow. It is worth
ing an adequate coronary perfusion pressure. Despite mentioning that DO2 commonly measured is a global
the benefits seen, it remains a challenge to implement measurement whereas it is probable that regional,
this management due to difficulties in identifying these organ-specific or microcirculatory areas are the ones
patients, scepticism and lack of resources. with compromised oxygenation. Nevertheless, it has

been shown repeatedly that augmenting global DO2 Identification of the high-risk patient has implica-
is beneficial. tions on management throughout the peri-operative
period. Defining high risk can be subjective and a
The extrapolation of this GDT in perioperative
variety of screening tests and scores have been used.
patients was introduced by Boyd et al. In their study
It has been suggested that a patient with an individual
of 107 surgical patients, 54 patients were randomized
mortality risk of greater than 5% or undergoing a pro-
to receive supranormal oxygen delivery as measured
cedure carrying 5% mortality be defined as a high-risk
by a pulmonary artery catheter. In this the study group
surgical patient3 .The table below is a simplified criteria
received a DO2 greater than 600 ml/min facilitated by
for identifying high risk patients.
the addition of an infusion of dopexamine. The results
showed a 75% reduction in mortality (5.7% vs 22.2 %) The P-POSSUM score (Portsmouth Physiologic
and a halving of the mean number of complications and Operative Severity Score enumeration of Mortal-
(0.68 % vs 1.35%) in the patients randomised to the ity), pre-operative risk stratification by the American
protocol group. Society of Anesthesiologists (ASA) score, and cardiac
risk scoring by Goldman Index, Detsky Index and Lee’s
Identification of the group targeted to receive
Index have been used.
GDT
Clinical criteria for high risk surgical patients

1 Severe cardiac /respiratory illness resulting in functional limitation
2 Extensive surgery for carcinoma involving bowel anastomosis
3 Acute massive blood loss > 2.5 litres
4 Age more than 70 yrs with moderate functional limitation of more than one organ system
5 Septicemia (positive cultures/septic focus)
6 Respiratory failure (PaO2 < 60 mmHg on FiO2 0.4, PaO2 /FiO2 < 150,ventilation > 48 hrs
7 Acute abdominal catastrophe
8 Acute renal failure( urea > 20 mmol/L, creatinine >260 mmol/L
9 Surgery for abdominal aortic aneurysm
Methods of achieving targets in goal directed the CVP may not reliably predict intravascular status
therapy in raised intra abdominal pressures, arrhythmias, with
the use of PEEP or in obstructive airways.
1. Optimum fluid level.
In the late 20th century, the pulmonary artery
2. Adequate cardiac output.
catheter (PAC) was extensively used. The rationale in
3. Supranormal oxygen delivery(DO2 , SCVO2) the use of the pulmonary artery catheter was a more
4. Oxygen extraction ratio > 27% accurate assessment of the volume status commensu-
rate to the LV function. The ability to ensure a DO2 that
5. Mean arterial pressure > 65 mm Hg (Inotropes
was supramaximal to ensure that oxygen debt does not
dobutamine)
occur at the tissue level. In addition the PAC has been
6. Urine output > 0.5 ml/kg/hr criticized that the PCWP and the ventricular response is
a curvilinear relationship that the PAOP approximating
7. Hemoglobin above 9.0 gms%
the LVEDP is presumptuous and that changes in the
What is an optimum fluid level and what monitor LV compliance are common in the critically ill.
can be reliably used to document this?
Sandham et al4 conducted a randomized con-
The central venous catheter has been long used to trolled trial comparing goal directed therapy in elderly
guide the fluid status of the individual. However recent patients, 60 years and older belonging to ASA grades
studies have challenged the usefulness of the CVP in 3 or 4, who electively or emergently underwent a major
predicting fluid responsiveness in a patient. In addition, surgery. The goals of directed treatment were in the

order of priority, an oxygen-delivery index of 550 to deviation of the arterial pressure ( σ AP) which is pro-
600 ml per minute per square meter of body-surface portional to the pulse pressure.
area, a cardiac index of 3.5 to 4.5 liters per minute per
The flotrac is simple and easy to use and needs
square meter, a mean arterial pressure of 70 mm Hg,
no calibration. The cardiac output is derived as the area
a pulmonary-capillary wedge pressure of 18 mm Hg,
under the curve and the systemic vascular resistance
a heart rate of less than 120 beats per minute, and a
derived from the CVP and cardiac output. The oxygen-
hematocrit of more than 27 percent. Assessment of the
ation indices (DO2 & DO2 I) can also be derived. The
achievement of these goals was based on the highest
flotrac is dependent upon the integrity of the arterial
value obtained. Suggested therapy for the achievement
tracing and is unsuitable in peripheral vasoconstriction
of the goals included, in order of priority, fluid loading,
and shock states. The SVV is reliable only in mechani-
inotropic therapy, vasodilator therapy, vasopressors for
cally ventilated patients without spontaneous breathing
hypotension, and blood transfusion for a hematocrit of
and is unreliable in the presence of arrhythmias.
less than 27 percent.
Meyer et al (5) randomized 60 high risk patients
1994 patients underwent randomization, 997 in
undergoing abdominal surgery into two groups, one
each group. The primary end point mortality was similar
receiving standard care and the other hemodynamic
in both groups (77 in the standard care and 78 in GDT).
optimization using cardiac index directed optimization
There was a higher incidence of pulmonary embolism
protocols using the flotrac (Vigileo) as the intervention
( 8 vs 0) in the GDT. The lengths of ICU stay in both
for cardiac ouput measurements. The standard care
the groups were similar at 10 days. The 6 month and
group had a MAP > 65 - 90 mm Hg, CVP between
12 month survivals were similar in both groups; the
8 - 12mmHg and urine output > 0.5 ml/kg/hr. In the
investigators concluded that there was no benefit in
intervention group, the cardiac index was maintained
the use of the PAC in the high risk elderly patients
above 2.5 L/min, and SVV monitoring to regulate the
undergoing surgery.
use of dobutamine or fluids accordingly. The median
Is the PAC still the gold standard in CO monitoring duration of hospital stay was significantly reduced
or are there other less invasive methods of mea- in the GDT-group with 15 (12 - 17.75) days versus
surements of cardiac output and oxygenation? 19 (14 - 23.5) days (P = 0.006) and fewer patients
developed complications than in the control-group [6
In the last decade, there has been at trend towards
patients (20%) versus 15 patients (50%), P = 0.03].
dynamic measurements of pressure versus static
The total number of complications was reduced in the
measurements. The dynamic parameters were derived
GDT group (17 versus 49 complications).The authors
after the passive leg raising test to determine the fluid
concluded that goal directed therapy using an arterial
responsiveness in hypotension. Monitoring equipment
waveform derived cardiac output improved outcomes
incorporated pulse pressure variations (LiDCO &
in high risk surgical patients.
PICCO) and stroke volume variations for determina-
tion of fluid status. In addition, oxygen delivery indices, Pulse power analysis is based on the theory that
measures of systemic vascular resistance and EPLW fluctuations of blood pressure about the mean are di-
have been incorporated in improved hemodynamic rectly related to the stroke volume (SV) ejected into the
monitoring. arterial system .The accuracy of this system is affected
by the non linear compliance of the arterial wall, the
The Flotrac (Vigileo) is a simple tool for assessment
wave reflection, efficiency of the transducer systems
of stroke volume variation (SVV) to predict fluid re-
and the aortic outflow which is continuous versus the
sponsiveness in surgery. This equipment has a unique
inflow that is pulsatile.
sensor and a processing unit. The flotrac analyses the
arterial trace 100 times per minute over 20 seconds. The LiDCO plus (Cambridge, UK) system is coupled
The data points are integrated with the patients demo- to a lithium dilution system, a technique first described
graphic profile and is used to calculate the standard by Linton et al in 1993. Either central or peripheral ve-

nous access may be used in addition to a peripheral catheter, typically placed in the femoral artery. Alter-
arterial line, to which a disposable lithium sensitive natively, the radial, axillary, or brachial artery may be
sensor is attached. The sensor membrane contains used; however, longer catheters are required to ad-
an ionophore which is selectively permeable to lithium. equately assess the aortic pressure wave signal from
The membrane voltage is related to the plasma lithium more distal sites.
concentration using the Nernst equation. The voltage is
The calibration is repeated to obtain a calibration
amplified and digitalized for analysis. Sodium supplies
factor for calculation of continuous CO, intrathoracic
the baseline voltage in the absence of lithium.
blood volume (ITBV) and extravascular lung water
The LiDCO plus monitor requires CO calibration (EVLW). Global end-diastolic volume (GEDV) is also
every 8 hours in addition to calibration after episodes measured and, together with ITBV, is representative
of hemodynamic instability. During calibration, isotonic of cardiac preload and EVLW. EVLW, comprising
lithium chloride (150mM) is given intravenously (0.02 intracellular, interstitial, and intra-alveolar water, is
to 0.04 mmol/kg). CO is derived from the dose and the measured intermittently using transpulmonary TD as
area under the concentration-time curve. Since lithium a means of quantifying pulmonary edema. Systolic
is only distributed in the plasma fraction of blood, for pressure variation and stroke volume variation (SVV)
the determination of CO, blood flow is determined by provide information about volume status in mechani-
dividing plasma flow by 1-packed cell volume, assessed cally ventilated patients.
on the basis of hemoglobin.
The accuracy of analysis is influenced by vas-
The accuracy of the Pulse CO algorithm may be cular compliance, aortic impedance, and peripheral
compromised in aortic reconstruction, regurgitation, arterial resistance. It is also influenced by arrhythmias,
use of balloon pump, arrhythmias, peripheral vaso- increased EVLW and aortic insufficiency. The pulse
constriction, inaccurate sodium and hemoglobin mea- contour analysis was found to correlate well with the
surements. In addition, a 1g/dl change in hemoglobin thermodilution based PA catheter derived CO in several
will contribute to an artifactual 4% change in cardiac surgeries including CABG.
output. Pearse et al have shown that the use of the
Esophageal doppler (ED) utilizes a flexible probe, at
LiDCO in high risk patients has contributed to improved
the tip of which is a transducer (4MHz continuous or
perioperative outcome.
5MHz pulsed wave). The probe may be left in place
Pulse contour analysis for CO measurement is for days to weeks in intubated, sedated, mechanically
based on the hypothesis that the area under the curve ventilated patients. When advanced to the mid-thoracic
of the systolic part of the arterial pressure waveform level, ideally between the 5th and 6th thoracic vertebrae,
is proportional to the stroke volume (SV). The area the device is parallel to and thus able to measure blood
under the systolic portion of the arterial pulse wave flow velocity in the descending aorta. It is assumed that
(measured from the end of diastole to the end of the the aorta is a cylinder and flow is calculated by multiply-
ejection phase) divided by the aortic impedance gives ing the cross-sectional area (CSa) by the velocity (Vf ).
a measure of the stroke volume, which multiplied by SV changes can be used to guide fluid administration.
the heart rate gives the cardiac output. ED also has the capability of determining the corrected
time flow (FTc), which is the systolic flow time corrected
The PiCCO system (PULSION Medical Systems)
for an HR of 60/min. This value, which represents the
is the first pulse contour device to be introduced into
time from the beginning of the aortic waveform upstroke
clinical practice external manual calibration of the sys-
to its return to baseline, is used as a measure of cardiac
tem is performed via transpulmonary thermodilution(TD)
preload. Good correlation with other techniques, such
every eight hours, or up to hourly during periods of
as pulmonary artery occlusion pressure, along with
hemodynamic instability. Blood temperature changes
improved outcomes has been documented.
from a thermo-indicator solution injected via a central
venous catheter are detected by a thermistor-tipped

End points of goal directed therapy
Identify the High Risk Surgical Patient- establish functional Capacity
Optimum managment of chronic disease and acute physiology
Institute flow monitoring and goal directed therapy pre & intraoperatively
ICU - ensure adequate oxygenation and hematocrit- Flow Monitoring
Oxygen delivery goals/tissue perfusion Goals (DO2 I > 600 ml/min/m2 & CI > 4.5 l/min/m2)
Current Evidences in the use of GDT Monitoring of Cardiac output : There is a trend to-
wards minimally invasive cardiac output monitoring and
Targeting a SCVO2 of greater than 70% in the
dynamic indices of variation in cardiac output(6) .Main-
postoperative period resulted in lesser morbidity and
tenance of cardiac output by fluid boluses of crystalloid
improved postoperative outcomes in surgical patients.
or colloid targeting the SCVO2 is recommended. If an
What measures should be taken to attain this target
inotrope is needed then dobutamine is the drug of
SCVO2? The SCVO2 measured at any time is a bal-
choice used in doses up to 20mcg/kg/min.Dopexamine
ance between oxygen delivery and utilisation and can
in a low dose was believed to improve outcomes in
be influenced by surgery, anesthesia, hemorrhage,
patients undergoing abdominal surgery, but Davies et
myocardial ischemia shivering etc. The Collaborative
al in a randomized study of dopexamine versus saline
study Group suggested that a higher target of 75%
in 124 patients with lowered anaerobic thresholds found
may be required in patients undergoing abdominal
no difference in outcomes or mortality.
surgery and that the SCVO2 decreases significantly
after surgery, hence more insights may emerge on Fluid Strategy in GDT: While the guidelines by Rivers
the most appropriate value targeted after surgery in suggest a liberal fluid administration strategy, the man-
the future. agement in post surgical patients may need caution.
Excess use of fluids particularly crystalloids is known
Role of central venous to arterial carbon dioxide
to e associated with bowel edema, and postoperative
difference: Futier and colleagues (7) conducted a sec-
ileus and prolonged postoperative recovery. Lobo et al
ondary analysis in a study involving 70 adult patients
randomized 88 patients undergoing abdominal surgery
(ASA I to III), undergoing major abdominal surgery,
to a restrictive group that received 4ml/kg/hr and the
and treated with an individualized goal-directed fluid
conventional group received 12 ml/kg/hour of Ringer’s
replacement therapy. All patients were managed to
lactate solution. A minimally invasive technique was
maintain a respiratory variation in peak aortic flow ve-
used to continuously monitor stroke volume and oxygen
locity below 13%. A total of 34% of patients developed
delivery index (DO2 I) in both groups. Dobutamine was
postoperative complications. They concluded that the
administered as necessary, and fluid challenges were
this difference in carbon dioxide (P(cv-a)CO2) was
used to test fluid responsiveness to achieve the best
significantly larger in the group with complications with
possible DO2 I during surgery and for 8 hours postop-
5 mmHg as the most predictive threshold value.
eratively. The study showed that while the DO2 I were
While SCVO2 reflects important changes in O2 similar in both groups, the complications were signifi-
delivery in relation to O2 needs during the periopera- cantly lesser in the restrictive than in the control group
tive period, a P(cv-a)CO2 < 5 mmHg might serve as a (20% vs 41.9%). They concluded that the preemptive
complementary target to SCVO2 during GDT to identify use of GDT targeting DO2 I with fluids, dobutamine and
persistent inadequacy of the circulatory response in a restrictive fluid policy resulted in improved outcomes
face of metabolic requirements when an SCVO2 ≥71% in the elderly undergoing major surgery.(8)
is achieved.

Conclusion 4. Sandham D.J, Hull R.D,Brant R.F et al. A randomised

Controlled Trial of the use of the Pulmonary Artery
Morbidity and mortality are high in some groups
Catheter in High Risk Surgical Patients.NEJM, January
of patients, particularly elderly patients with low cardio
2, 2003, Vol #, 48 , No1.
respiratory reserves who undergo extensive noncardiac
surgery. Perioperative alterations in DO2 are closely 5. Mayer A, Boldt J, Mengistu A et al: Goal Directed Intra-
correlated to the development of multi organ failure and Operative therapy based on Autocalibrated Arterial
death. Several studies outlined above have convinc- pressure waveform analysis reduces the Length of Hos-
ingly shown improvements in outcome with GDT in the pital stay in High risk Surgical patients. A randomised
postoperative period. Controversies on the exact target controlled study. Critical care 2010.
value of SCVO2 and the choice and amount of fluid 6. Lee A.J,Cohn H.J, Ranasinghe S.J:Cardiac Output
continue and need to be tailored to individual cases. assessment by Invasive and Minimally Invasive Tech-
Insight into the concepts of oxygen delivery and niques. Anesthesiology Research and Practice. Vol
tissue utilization have strengthened the postoperative 2011.Article ID475151.
care of the high risk groups of patients. 7. Futier E,Robin E,Jabaudon M,etal: Central venous
References Oxygen Saturation and Venous to Arterial Carbon
dioxide difference a a Complementary tool for Goal
1. Rivers E,Nguyen B, Havsted S, et al. Early Goal Di-
directed Therapy in High Risk surgery. Critical Care
rected Therapy in the treatment of severe sepsis and
2010:14:R193.
Septic Shock. NEJM Nov 8,2001.Vol 345.No:19.
8. Lobo M.S,Ronchi S.L,Oliviera E.N et al:Restrictive
2. Pearse R, Dawson D, Fawcett J et al: Early Goal Di-
Strategy of Intra-Operative Fluid Maintenance dur-
rected therapy after Major Surgery reduces complica-
ing Optimisation of Oxygen Delivery Reduces Major
tions and Duration of Hospital Stay. Critical care 2005,9:
Complications after High Risk surgery. Critical care
R 687-693.
2011:15;R226.
3. Nicholas L, Hamilton M, Rhodes A: Clinical Review.
Goal Directed therapy in High Risk Surgical Patients.
Critical care 2009;13 :231.

Anesthesia for Patients with Valvular Heart
Disease for Non Cardiac Surgery 94 Ranjith Karthekeyan B
01 ANESTHESIA FOR PATIENTS WITH VALVULAR HEART

DISEASE FOR NON CARDIAC SURGERY
Associate Professor Ranjith Karthekeyan B
SRMC,
Chennai
Valvular heart disease (VHD) is characterized by decrease flow. With regurgitant lesions, the goal is to
damage to or a defect in one of the four heart valves: reduce or minimize regurgitant transvalular flow; with
the mitral, aortic, tricuspid or pulmonary. VHD is found stenotic lesions, the goal is to maximize and enhance
in 4% of patients over the age of 65 in the developed stenotic transvalular flow.
world. The mitral and aortic valves are the ones most
Causes
frequently affected by valvular heart disease. Normal
cardiac valves permit unidirectional blood flow without There are many different types of valve disease;
causing obstruction or regurgitation, trauma to blood some types can be present at birth (congenital), while
elements, thromboembolism, or excessive mechani- others may be acquired later in life.
cal stress on the valve and heart. In VHD, the valves • Rheumatic fever may cause valvular heart dis-
become too narrow and hardened (stenotic) to open ease.
fully, or are unable to close completely (incompetent)
• Bacterial endocarditis, an infection of the inner
disrupting this relationship.
lining of the heart muscle and heart valves (endo-
VHDs affect cardiac function mainly by causing cardium), is a cause of valvular heart disease.
abnormal loading conditions. Common to all VHDs is
• High blood pressure and atherosclerosis may
an initial period of compensation of the cardiac cham-
damage the aortic valve.
bers to maintain normal cardiac output in the face of
abnormal loading conditions. With the progress of the • A heart attack may damage the muscles that
disease however, compensation reaches a maximum control the heart valves.
and decompensation and cardiac failure follows. VHD
• Heart valve tissue may degenerate with age.
is frequently encountered by the anesthesiologists.
Maintaining cardiovascular stability with optimal he- • Other disorders such as carcinoid tumors, rheu-
modynamic parameters and adequate systemic per- matoid arthritis, systemic lupus erythematosus, or
fusion pressure during the anesthetic management of syphilis may damage one or more heart valves.
patients with valvular heart disease can be extremely • Methysergide, a medication used to treat migraine
challenging. With the high incidence and severity of headaches, and some diet drugs may promote
complications in this subgroup of patients, a concise valvular heart disease.
understanding of all relevant factors affecting myocar-
dial performance with valvular pathology is necessary. • Radiation therapy (used to treat cancer) may be
The goal in VHDs is to maintain the compensatory associated with valvular heart disease.
mechanisms intact. Important factors that govern blood • Other causes of valve disease include: coronary
flow across a valve include: a) valve area; b) square artery disease, cardiomyopathy (heart muscle
root of the hydrostatic pressure gradient across the disease), hypertension, aortic aneurysms, and
valve; and c) duration of flow whether systole or di- connective tissue diseases
astole. The valve area of many regurgitant lesions
In this review we will consider the circulatory
changes in response to loading conditions (preload,
pathophysiology of mitral and aortic valves disease, as
afterload) whereas valve area with stenotic lesions
these represent the majority of patients with valvular
is generally fixed. Larger values of these factors will
heart disease.
increase transvalvular flow; reducing these factors will

Mitral stenosis (MS) sure and volume upstream of the valve. Initially the left
atrium dilates keeping the pulmonary artery pressure
Etiology
low. As disease progresses, pulmonary artery pressure
Mitral stenosis is usually a delayed complication increases and medial hypertrophy develops result-
of rheumatic fever and usually becomes functionally ing in chronic reactive pulmonary hypertension. The
significant within 2 decades. Most patients (66%) are right heart hypertrophies to pump against a pressure
female. Majority of them have combined stenosis overload, then fails. Secondary pulmonary / tricuspid
and regurgitation lesion (40%) than isolated stenosis regurgitation develops. . The left ventricle functions
(25%). normally but is small and poorly filled.
Pathyophysiology Normal valve surface area 4 – 6 cm2
As mitral valve orifice area decreases, the left Symptom free until 1.5 – 2.5 cm2
atrial-ventricular pressure gradient must increase,
Moderate stenosis 1 – 1.5 cm2
causing atrial dilation with fibrillation in 30% - 70% of
patients depending on patient age. Mitral valve stenosis Severe stenosis <1 cm2,
under fills the left ventricle and increases both pres-
Critical stenosis < 0.8 cm2
Obstruction to LA emptying
Difficulty in LV
filling LA pressure Change in LA
function
Pulmonary venous pressure
Perivascular edema Pulmonary artery pressure

Luminal narrowing
Reversal of pulmonary Cardiac Stable with mild

blood flow output symptoms
Severe pulmonary
Pulmonary compliance hypertension
Work of breathing
Pulmonary vascular resistance
RV overload
Mitral stenosis Tricuspid regurgitation
The Gorlin formula for determination of the mitral valve Therefore, TPG = (CO/ DFT) . 2
area is as follows:
TPG = transvalvular pressure gradient, TFR =
transvalvular flow rate, CO = cardiac output, DFT =
diastolic filling time. Rapid heart rates, especially with
where 0.85 is the mitral orifice constant atrial fibrillation, decrease diastolic filling time and mark-
TPG α (TFR)2 . edly decrease cardiac output. An increased trans-mitral
pressure gradient – leads to pulmonary congestion.LV
TFR = CO/ DFT. filling is optimised by a slow heart rate.

Mitral valve replacement should generally be per- Investigations

formed when patients are symptomatic and the valve
• ECG: P mitrale (left atrial enlargement) if sinus
area is less than approximately 1.5 cm2. Percutaneous
rhythm. Atrial fibrillation may be present.
balloon valvuloplasy may be an alternative to surgery,
and may be particularly valuable in the high-risk patient • CXR: valve calcification. Large left atrium (lateral
who needs an urgent noncardiac procedure. film). Double shadow behind heart on PA film.
Splaying of the carina. Kerley B lines indicating
Pressure volume loop
pulmonary congestion.
• Echocardiography: Measures the gradient and
valve area. Pulmonary hypertension is likely if
the left atrial pressure is chronically above 25
mm Hg.
Treatment
When symptoms of mild mitral stenosis develop, diuret-
ics - can decrease the left atrial pressure and relieve
symptoms.
If atrial fibrillation develops - heart rate control may be
achieved with digoxin, β-blockers, calcium channel
blockers, or a combination of these medications.
Anticoagulation - is required in patients with mitral
Due to the restriction of flow from the left atrium
stenosis and atrial fibrillation because the risk of em-
to the ventricle, patients with significant mitral stenosis
bolic stroke in such patients is about 7% to 15% per
have reduced LVEDV and LVEDP. Stroke volume also
year.
is reduced. The actual LV performance is relatively
normal. The limitation of stroke volume in these patients Warfarin - is administered to a target international
is entirely due to inadequate filling of the LV. normalized ratio (INR) of 2.5 to 3.0.
History Surgical correction of mitral stenosis is indicated

when symptoms worsen and pulmonary hypertension
• Dyspnea, hemoptysis, recurrent bronchitis
develops.
Examination
Anesthetic considerations
• Mitral facies - malar flush on cheeks
HR- keep slow to allow for diastolic filling; avoid sinus
• Peripheral cyanosis tachycardia. Treat tachycardia aggressively with beta
blockers.
• Signs of right heart failure (elevated JVP, he-
patomegaly, peripheral edema, ascites) Rhythm - sinus rhythm; Immediate cardioversion if
atrial fibrillation occurs peri-operatively
Tapping apex beat, loud first heart sound, open-
ing snap (if in sinus rhythm) and low pitched diastolic Preload - maintain to help with left ventricular filling;
murmur heard best at the apex with the bell of the excess preload may cause pulmonary edema.
stethoscope.
Afterload- SVR should be maintained; avoid decreases
Opening Snap in SVR; avoid increases in PVR. Hypoxia, hypercarbia,
lung hyperexpansion, or nitrous oxide, can worsen right
heart failure.
S1 S2

Contractility-maintain to provide adequate cardiac causes. Secondary MR is caused by functional lesions

output of the myocardium such as ischemia, infarction, dilated
cardiomyopathy, or endocarditis- chronic causes.
Oversedation should be avoided, and supplemen-
tal oxygen in the preoperative period by nasal cannula Pathophysiology
may be beneficial. Premedication should be light to
The pathophysiology of MR is volume overload
avoid an acute decrease in preload or the possibility
of the LV the circulatory compensation is peripheral
of sedation with resultant hypoxemia and hypercapnia.
vasodilatation to promote forward rather than backward
Avoidance of an anticholinergic should be considered
flow. As much as 50% of the left ventricular volume
to minimize tachycardia. Due to the inherent limitation
flows into a massively dilated left atrium through the
of preload reserve across a stenotic valve, inotropic
incompetent mitral valve before the aortic valve opens.
drug infusion with dobutamine or epinephrine may
Left ventricular ejection fraction is therefore supranor-
be necessary to maintain stroke volume as long as
mal. With chronic MR the LA dilates over decades,
tachycardia is avoided. Anticipate bleeding complica-
maintaining a low left atrial pressure until late in the
tions from chronic anticoagulation in patients with atrial
disease and thereby avoiding pulmonary congestion.
fibrillation.
As the regurgitant fraction exceeds 60% of the stroke
Mitral regurgitation (MR) volume, forward cardiac output becomes compromised
and symptoms of “forward” heart failure (fatigue, weak-
Etiology
ness) occur. Acute mitral regurgitation (from papillary
Mitral regurgitation (MR) is the most commonly en- muscle rupture, for example) occurs in a heart where
countered valve lesion in modern clinical practice(5). Pri- the LA cannot rapidly dilate to accommodate the regur-
mary MR results from abnormalities of the mitral valve, gitated blood. As a result there is a rapid increase in LA
subvalvular apparatus, or cardiac skeleton caused by pressure and LVEDP. This can cause acute pulmonary
myxomatous degeneration, rheumatic disease, fenflu- edema, pulmonary hypertension, and RV dysfunction
ramine diet suppressants (>90 day medication) – acute or failure
Volume overload of LA
Volume overload of LV
LA dilation
Early Late
Normal LA
LV filling Fiber size pressures Contractility
Stroke volume BP and CO
Cardiac output and BP
Reflexive arteriolar
maintained
constriction
SVR
Forward flow Regurgitation
LA pressure Pulmonary
congestion
Mitral regurgitation

The amount of MR depends on the pressure Examination

gradient between the left ventricle and atrium, the
• Displaced and forceful apex (the more severe
mitral valve orifice size, afterload and the duration
the regurgitation the larger the ventricle)
of systole. A moderately increased heart rate (>90
bpm) decreases the time for regurgitation in systole • Soft first heart sound, apical pansystolic mur-
and decreases the time for diastolic filling reducing LV mur radiating to the axilla, loud third heart
overload. Because systolic ejection is partly into the low sound
pressure LA, the ejection fraction is a poor indicator of
LV function – an LVEF less than 50% means severe
S1 S2
dysfunction. Onset of symptoms of forward heart failure
is associated with a very high 5 year mortality .A reduc- • Atrial fibrillation
tion in left ventricular ejection fraction below 60% or an
Investigations
increase in end-systolic dimension exceeding 45 mm
indicates the need for surgical intervention with valve • ECG: left atrial enlargement. Atrial fibrilla-
repair or replacement. The presence of MR has been tion.
identified as a strong positive predictor of subsequent • CXR: left atrial and left ventricular enlarge-
morbidity and mortality after myocardial infarction. ment. Mitral annular calcification.
Pressure volume loop • Echocardiography assesses the degree of
regurgitation. It may also show thrombus in the
enlarged left atrium. (Transesophageal echo
particularly useful as mitral valve close to the
esophagus). Since total stroke volume con-
sists of both forward and regurgitant volumes,
ejection fraction values may overestimate left
ventricular contractility.
Anesthetic considerations
Goals
Heart rate -High normal
Rhythm – maintain sinus rhythm
showing markedly increased left ventricular end- Preload - maintained
systolic and end-diastolic volumes, along with some
increase in left ventricular end-diastolic pressure. The Afterload – avoid increase in afterload, maintain
eccentric hypertrophy of the ventricle allows preserva- low SVR, Low PVR
tion of forward stroke volume by increasing total stroke Contractility – maintained, avoidance of myocar-
volume. Blunting of the LV pressure increase during dial depression.
LV contraction occurs secondary to rapid early runoff
of LV volume into the low-pressure left atrium MR may be a hemodynamic emergency requir-
ing immediate surgery. Forward cardiac output is best
History
when the heart is full and reasonably fast, and the blood
• Fatigue, weakness, pressure is low-normal. Determination of the optimal
end-diastolic volume or pressure is difficult without a
• Dyspnea
PAC or TEE, and may require observing the response
to a fluid load. Bradycardia is associated with an in-

crease in ventricular size leading to valvular dilatation overcome the stenosis, but aortic pressures are normal.
and an increase in regurgitant fraction, so should be Because of the decreased compliance, LV filling during
avoided. Maintain a low “afterload” as determined by diastole depends on adequate preload as well as atrial
blood pressure. Patients with MR often require inotropic contraction. While the latter contributes less than 20%
assistance to accomplish these hemodynamic goals in of filling in the normal heart, it may contribute twice this
the face of general anesthesia. In advanced disease amount in AS.
pulmonary hypertension is common thus avoid factors
This phase of AS is termed “mild” stenosis with
that increase pulmonary artery pressure (hypoxia,
physiologic compensation. As the aortic valve area
hypercarbia, high inspiratory pressures, acidosis).
diminishes below 1 cm- down to 0.5 cm the stenosis
Premedication should be used judiciously because
is termed “moderate.” Patients begin to develop symp-
oversedation can lead to hypercapnia and marked
toms as the heart struggles to maintain flow through the
increases in pulmonary vascular resistance. Nitric ox-
narrowing lesion. The increased work of the heart in
ide, as a specific pulmonary artery dilator, may have
association with decreased compliance and increased
an important role in the management of patients with
LVEDP results in angina and myocardial ischemia due
reversible pulmonary hypertension. Hyperventilation is
to increased oxygen demand and wall tension in the
a second therapeutic modality available for selectively
hypertrophied left ventricle. 30% of patients who have
dilating the pulmonary vasculature without affecting the
aortic stenosis with normal coronary arteries have an-
patient’s systemic blood pressure. Prostaglandin E1
gina. Upto 50% of patients may have significant CAD.
also has been used but is accompanied by a decrease
Sub-endocardial ischemia may exist as coronary blood
in systemic pressure. Anesthetic agents that lead to
supply does not increase in proportion to the muscular
decreased contractility should be avoided. High-dose
hypertrophy.
narcotic relaxant anesthetics are used most com-
monly. Obstruction to LV ejection
Aortic stenosis Pressure overload
Etiology Early LV mass Later
Congential - bicuspid aortic valve (2%). Acquired LV compliance Fibrosis, contractility

due to rheumatic heart disease or valve calcification Contractility maintained
(most common). Incidence is high in males. Nearly half
Preload mechanism LV dilation
of all men over the age of 85 years have aortic sclerosis
with significant stenosis in 4%. An increased incidence Atrial “booster pump”
with aging is secondary to greater mechanical stress Maintenance of normal SV SV

over time as well as longer risk factor exposure. These
patients are generally older, hypertensive males with
Aortic stenosis
a prior history of smoking, diabetes, and hypercholes-
terolemia.
Aortic valve area
Pathophysiology
Normal 2.6 - 3.5 cm2
The gradual process of narrowing of the aortic
orifice leads to concentric left ventricular hypertrophy Mild 1.2 – 1.8 cm2
and a reduction in left ventricular compliance – the Moderate 0.8 – 1.2 cm2
myocardium becomes thick, the end-diastolic pressure
Significant 0.6 .0.8 cm2
(LVEDP) rises, whereas the LV end-systolic volume
stays relatively normal. As the pressure gradient Critical < 0.6 cm2
across the aortic valve develops, stroke volume is
preserved by an increase in LV systolic pressures to

LV-Aortic Gradient Examination

Mild 12 – 25 mmHg • Slow rising pulse with narrow pulse pressure
Moderate 25 - 40 mmHg • Ejection systolic murmur maximal at the 2nd inter-
costal space, right sternal edge radiating to the
Significant 40-50 mmHg
neck
Critical > 50 mmHg
Primary risk factors for AS are aortic jet flow ve-
locity > 4.5m/sec and left ventricular ejection fraction S1 S2
<50%. Other associated factors include patient age
(>50 years old), the extent of aortic calcification, and Investigations
the annual serial progression of change in aortic flow • ECG will show left ventricular hypertrophy and
velocity (>0.3 m/sec/yr). Recently, the severity of AS strain (with secondary ST-T wave abnormali-
and left ventricular dysfunction have been correlated ties)
with serum levels of brain natriuretic hormone. Hyper-
tension produces an additive load on left ventricular • CXR remains normal until the left ventricle begins
ejection and requires aggressive management. to fail. Post stenotic dilatation of the aorta and a
calcified aortic annulus may be seen.
• An echocardiogram will enable calculation of
valve gradient (see above) and a quantitative as-
sessment of left ventricular performance. Aortic
blood flow velocity increases proportionately with
AS severity so that patients can be followed by
periodic echocardiographic examinations.
• Cardiac catheterisation may be used to estimate
the gradient across the valve. It will also give
information about any concurrent coronary artery
disease.
Treatment
• CHF
Digoxin
showing markedly elevated left ventricular systolic
pressure, elevated end-systolic and end-diastolic vol- Sodium restriction
umes, and increased diastolic pressure. Small doses of diuretics
History • Surgical intervention
• Angina, Valve replacement is recommended when the
• Breathlessness valve area is less than 0.8 cm. Percutaneous balloon
valvuloplasty is possible in selected patients. Symp-
• Syncope
tomatic patients for elective non-cardiac surgery should
• Cardiac failure have aortic valve replacement first as they are at great
Symptoms do not correlate well to the severity of risk of sudden death perioperatively (untreated severe
stenosis; some patients with small valve areas can be symptomatic stenosis has a 50% one year survival).
asymptomatic. Asymptomatic patients for major elective surgery as-

sociated with marked fluid shifts (thoracic, abdominal, Aortic Regurgitation

major orthopedic) with gradients across the valve > 50
Etiology
mmHg should have valve replacement considered prior
to surgery. Asymptomatic patients for intermediate or Causes of primary aortic regurgitation (AR) in-
minor surgery generally do well if managed carefully. clude diseases that affect the aortic leaflets such as
rheumatic heart disease, endocarditis. With rheumatic
Anesthetic Considerations
disease there may be combined stenosis and regurgi-
Goals tation. Secondary aortic regurgitation is due to aortic
dissection and connective tissue disorders that dilate
HR- Maintain low HR (70-80) to control oxygen utili-
the aortic root (tertiary syphilis, Marfan’s syndrome
zation and prevent myocardial ischemia; severe bra-
and ankylosing spondylitis), trauma, and appetite
dycardia is associated with decreased cardiac output
suppressant medications as well as aortic root pathol-
because stroke volume is fixed; avoid bradycardia
ogy secondary to annulo aortoectasia from aging and
Rhythm- maintain sinus rhythm. SVT require cardio- chronic hypertension. The latter mechanism is most
version common.
Preload- Maintain or increase to provide adequate filling Pathophysiology
and cardiac output
The pathophysiology of AR is combined pressure
Afterload- Maintain to keep coronary perfusion pres- and volume overload, which significantly increases
sure stable; avoid sudden increases or decreases in wall stress during both systole and diastole. volume
SVR. overload of the left ventricle secondary to the regurgi-
Contractility- maintained tant volume per se. The left ventricle generates a very
large stroke volume, aided by peripheral dilatation,
spinal and epidural anesthesia are contraindicated in
to make up for the backwards flow through the aortic
patients with severe aortic stenosis due to a decreased
valve during diastole. Pressure overload results from
SVR.
systemic hypertension as a result of increased total
Elevated filling pressures and sinus rhythm are aortic stroke volume ejected during systole The heart
required to fill the non-compliant left ventricle. Properly rate is usually elevated as this reduces the proportion
timed atrial contractions contribute as much as 40 % to of time spent in diastole (when regurgitation occurs).
left ventricular preload in patients with aortic stenosis With severe, compensated AR the regurgitant flow may
(normal = 20%). Rhythms other than sinus may pro- exceed 20 L/min, giving a total cardiac output of 25 L/
duce a critical reduction in cardiac output as impaired min. The left ventricle adapts with eccentric hypertrophy
filling of the left ventricle causes a fall in stroke volume. where sarcomeres are laid down in series and myofi-
Tachycardia is detrimental as it may produce ischemia. brils elongate thereby preserving ventricular diastolic
Premedication should be light, and chest pain in the compliance. Once preload reserve is exhausted and
preoperative period should be managed with supple- the hypertrophic response with eccentric hypertrophy
mental oxygen and no nitrates because of venodilation. becomes inadequate, any further increase in afterload
Systemic hypotension causing a reduction in coronary can reduce stroke volume and ejection fraction, thereby
perfusion pressure should be vigorously managed with causing symptoms of exertional angina and congestive
careful volume replacement and/or a vasoconstrictor failure.
such as phenylephrine .Postoperatively, effective pain
The regurgitant volume depends directly on the
management is essential as it avoids catecholamine
regurgitant orifice area, the square root of the diastolic
induced tachycardia and hypertension and the risk of
pressure gradient across the valve, and the diastolic
cardiac ischemia and patients should be appropriately
time interval. Theoretically, increasing heart rate should
monitored until fluid shifts have stabilized.
improve net forward flow by decreasing the diastolic
time interval. However, any reduction in regurgitant

volume/beat is offset by the increase in beats/min so

that total regurgitant volume/min remains constant.
LVvolumeoverload
Fiberlength,LVvolume
EFmaintained
Velocityofinjection Lowoxygencost
Rapidofwalltension
Later
Increasedwalltension,Mass
Stiffness Contractility
LApressure Strokevolume
Changeinfunctioncurve
Aortic insufficiency


Loop A, from a patient with acute aortic insuf- Anesthetic considerations

ficiency, shows moderately elevated left ventricular
HR- Avoid bradycardia; mild tachycardia - an increase
systolic and diastolic volumes as well as an increase in
(10-15 beats) causes shortening of diastolic phase
ventricular volume during ventricular relaxation. Loop
which decreases the regurgitant fraction and increases
C, from a patient with chronic aortic insufficiency, shows
cardiac output
markedly increased systolic and diastolic volumes but
lower end-diastolic pressure. Rhythm- sinus rhythm preferred
History Preload- maintain or increase to maximize forward

cardiac output and maintain blood pressure
• Dyspnea, secondary to pulmonary conges-
tion Afterload- decrease afterload to favor forward cardiac
output (keep moving forward); avoid sudden increase
• Palpitations
in afterload
Examination
Contractility- maintain, avoid myocardial depression.
• Widened pulse pressure due to increased sys-
Most patients tolerate spinal or epidural provided in-
tolic pressure; decreased diastolic pressure.
travascular volume is maintained
• Collapsing (‘waterhammer’) pulse. Corrigan’s
Vasodilators by lowering afterload increase for-
Sign - visible neck pulsation. De Musset’s
ward flow, decrease left ventricular size and enhance
Sign - head nodding. Quincke’s Sign - visible
ejection fraction. Unlike AS, patients with severe
capillary pulsations in the nail beds
regurgitant disease may live many years; the amount
Diastolic murmur loudest in the 2nd intercostal of regurgitation alone is not indicative of the stage
space at the right sternal edge of disease. The appearance of symptoms follows a
rise in LVEDP and progressive LV dysfunction, which
may not be reversible. Once shortness of breath be-
gins to occur, mortality is common within 2-4 years.
S1 S2 Asymptomatic patients usually tolerate non-cardiac
surgery well. Patients with a functional capacity less
Investigations
than 4 MET’s (unable to climb a flight of stairs or walk
• CXR shows cardiomegaly with a boot shaped on level ground at greater than 6 km/hr) need to be
heart considered for valve replacement surgery first. Treat
• ECG shows the voltage criteria for left ven- SVT / atrial fibrillation if associated with hypotension
tricular hypertrophy promptly with synchronized DC cardioversion. Persis-
tent bradycardia can be treated with beta-agonists.
• Echocardiography gives qualitative analysis
Intra-arterial pressure monitoring is useful for major
of the degree of regurgitation
surgery. Acute afterload reduction can be beneficial if
Treatment combined with preload augmentation. Premedication
is often associated with venodilation and a reduction
Once symptomatic, death can occur within 5 years
in heart rate which may not be an advantage. While
unless lesion is surgically repaired.
reductions in contractility are undesirable in almost all
Digitalis, diuretics and afterload reduction (ACE in- valvular disease conditions, for AR the maintenance
hibitors) for chronic cases (eventual surgical repair). of adequate preload and reduced afterload are most
Inotropes (dopamine, dobutamine) and vasodila- important. When using vasodilator drugs this must be
tor for severe, chronic aortic regurgitation (requires kept in mind: nitroglycerin may be of little or no benefit,
surgery) while nitroprusside or other arterial dilators significantly
improve forward flow and reduce LVEDP. Maximizing

forward cardiac output with the correct balance of af- Aortic stenosis and mitral stenosis. Pathophysiologi-
terload reduction and preload augmentation is difficult cally, the progression of the disease follows a course
to gauge without a PAC. The period of emergence similar to that seen in patients with pure mitral stenosis
which is associated with pain and hypertension is of with development of pulmonary hypertension and,
particular concern, as this may be associated with an eventually, RV failure. Symptomatology is primarily
acute rise in LVEDP and pulmonary edema. Unlike referable to the pulmonary circuit, including dyspnea,
AS where the reduction in blood pressure may be life hemoptysis, and atrial fibrillation. This combination of
threatening, epidural or spinal anesthesia may be a valvular heart disease may lead to underestimation of
good choice for appropriate patients and surgeries in the severity of the aortic stenosis because the aortic
patients with compensated AR. valve gradient may be relatively low because of low
aortic valvular flow. Such a combination of lesions can
I. Mixed valvular lesions. For all mixed valvular be extremely serious because of the limitations of blood
lesions, management decisions emphasize flow at two points.
the most severe or the most hemodynamically
significant lesion.
1. Hemodynamic management
LV Heart Contractile Systemic Pulmonary

preload rate state vascular vascular
resistance resistance
Mitral Ĺ Ļ Maintain Ĺ Ļ
stenosis
alone
Aortic Ĺ Ļ Maintain Ĺ Maintain
stenosis
alone
Typical Ĺ Ļ Maintain Ĺ Ļ
management
for combined
lesion
a. The best hemodynamic management for a pa- concentration should be supplied to minimize
tient with both aortic and mitral stenosis includes pulmonary vasoconstriction.
preload augmentation, normal-to-low heart b. Aortic stenosis and mitral regurgitation. This
rates, and preservation of contractility. Due combination is relatively rare but should be sus-
to the high risk of decreased coronary perfusion, pected in patients with aortic stenosis who also
systemic vascular resistance must be increased have left atrial enlargement with atrial fibrillation.
whenever the diastolic perfusion pressure falls. Mitral regurgitation can be exacerbated by LV
All agents or conditions that might augment dysfunction due to severe aortic stenosis. In this
pulmonary vascular resistance must be aggres- situation, the mitral valve does not require replace-
sively avoided. PCO2 should be maintained in ment, and the mitral regurgitation regresses after
the low-to-normal range, and a high inspired O2 the aortic valve is replaced.


stenosis
alone
Mitral Ĺ,Ļ Ĺ Maintain Ļ Ļ
regurgitation
alone
Typical Ĺ Maintain Maintain Maintain Ļ
management
for combined
lesion
2. In managing these patients, the hemody- rate should be kept at least in the normal range,
namic requirements for aortic stenosis and and tachycardia should be avoided at all costs.
mitral regurgitation are contradictory. Because Contractility should not be depressed, and condi-
aortic stenosis most frequently will lead tions or pharmacologic agents that increase pul-
these patients into deadly intraoperative monary vascular resistance should be avoided.
situations, it should be given priority when
C. Aortic stenosis and aortic regurgitation. The
managing the hemodynamic variables.
combination of aortic regurgitation and aortic
stenosis is not well tolerated because it provides
Preload augmentation normally is beneficial
the LV with both severe pressure and volume
and, for coronary perfusion, maintenance of at
overloading. These stresses lead to major in-
least normal afterload is desirable. Obviously,
creases in myocardial O2 consumption (MvO2)
increased systemic vascular resistance may hurt
and, as might be expected, angina pectoris is an
forward flow, but the stenotic aortic valve provides
early symptom with this combination. Once symp-
the primary impedance to forward flow no matter
tomatology develops, the prognosis is similar to
what the systemic vascular resistance is. Heart
that of pure aortic stenosis.

stenosis
alone
Aortic Ĺ Ĺ Maintain Ļ Maintain
regurgitation
alone
Typical Ĺ Maintain Maintain Maintain Maintain
management
for combined
lesion

2. Normally, augmentation of preload is beneficial vascular resistance should be augmented when-

for both aortic stenosis and aortic regurgitation. ever systemic pressures begin falling to preserve
However, the hemodynamic requirements for coronary blood flow. Maintaining a normal heart
afterload and heart rate for these two lesions rate, contractility, and pulmonary vascular resis-
are contradictory. Generally, maintaining a tance will help stabilize the patient.
hemodynamic profile consistent with aortic
D. Aortic regurgitation and mitral regurgitation.
stenosis is logical because compromise of this
The combination of aortic and mitral regurgitation
lesion intraoperatively is potentially more deadly
occurs frequently, and this combination can cause
than increasing the aortic regurgitation. Despite
rapid clinical deterioration.
the risk of decreasing cardiac output, systemic

regurgitation
alone
Aortic Ĺ Ĺ Maintain Ļ Maintain
regurgitation
alone
Typical Ĺ Ĺ Maintain Ļ Maintain
management
for combined
lesion
2. The hemodynamic requirements of aortic regur- E. Mitral stenosis and mitral regurgitation. Rheu-
gitation and mitral regurgitation are similar. The matic mitral stenosis rarely is pure and commonly
primary problem is providing adequate forward exists in conjunction with mitral regurgitation.
flow and peripheral circulation. The development When dealing with patients with combined mi-
of acidosis leading to peripheral vasoconstriction tral stenosis and mitral regurgitation, decisions
and increased impedance to LV outflow can lead concerning hemodynamic management must
to rapid clinical deterioration. Therefore, keeping consider which lesion is predominant. As a rule
the systemic vascular resistance relatively low of thumb, normalization of afterload, heart rate,
while maintaining adequate perfusion pressure and contractility, while avoiding agents or condi-
is the fine clinical balance needed until cardio- tions that lead to reactive pulmonary constriction
pulmonary bypass can be initiated. and providing adequate preload, leads to optimal
hemodynamic stabilization.


Mitral Ĺ Ļ Maintain Maintain Ļ
stenosis
alone
regurgitation
alone
Typical
management
Maintain maintain
for combined Ĺ Maintain Maintain
lesion

Anesthetic Management of Congenital
Diaphragmatic Hernia (CDH) 108 M Subrahmanyam
01 ANESTHETIC MANAGEMENT OF CONGENITAL

DIAPHRAGMATIC HERNIA (CDH)
HOD of Anesthesia, Rainbow Hospitals M Subrahmanyam
Axon Anesthesia Associates
Hyderabad
Introduction referred to as Bochdalek hernia in honor of Victor Boch-

dalek’s contribution to the field. In 1977, extracorporeal
Congenital diaphragmatic hernia (CDH) usu-
membrane oxygenation (ECMO) was introduced as a
ally presents as a life threatening emergency which
treatment for neonates with respiratory failure refrac-
requires rapid resuscitation; correction of acidosis,
tory to conventional care, and its application in the field
fluid deficit, thermoregulation etc. CDH occurs in ap-
of CDH has increased the survival rate of infants born
proximately 1:2500 to 1:5000 live births, with a male to
with CDH according to some authors.
female ratio of 2:1. Left diaphragm is more often (>85%)
involved than right. Survival rates for isolated CDH in Pathophysiology of CDH
the best centres of the world vary between 60-70%. In
The spectrum of clinical presentation varies,
around 40% cases there are associated anomalies,
depending upon the period of lung invasion and pul-
further decreasing survival.
monary agenesis. Contrary to earlier thought, it is now
History believed that the primary pathology is the pulmonary
hypoplasia, which leads to developmental defect in
The first description of CDH was in 1679 by La-
the diaphragm, leading to herniation of the abdominal
zarus Riverius who incidentally noted a CDH during
viscera into the pleural cavity. This causes mediastinal
a postmortem examination of a 24-year-old person.
shift with consequent effects. Presentation depends on
In 1848, Victor Alexander Bochdalek, a professor
the development of pulmonary hypoplasia and pulmo-
of anatomy at Prague, described both right and left
nary vasculature.
posterolateral CDH. To this day, CDH commonly is

There are fewer alveoli, thickened alveolar walls, Another variation of this index is the O/E LHR or the
increased interstitial tissue, and markedly diminished observed/expected LHR.
alveolar air space and gas exchange surface area.
Outcomes can be predicted as follows
There are a reduced number of vessels, adventitial
thickening, medial hyperplasia, and peripheral exten- • Fetuses with an O/E LHR less than 15% have
sion of the muscle layer into the smaller intra-acinar virtually no chance to survive, such that the hy-
arterioles. Although both lungs are affected, the ipsi- poplasia is extreme. The liver is typically up in
lateral one is affected more so than the contralateral these cases. Morbidity rates in these patients are
one. These morphologic changes only become obvi- unknown, given the few reported cases.
ous when the lung becomes functional at birth. They • Fetuses with an O/E LHR from 15% to 24.9% have
lead to variable degrees of respiratory insufficiency severe pulmonary hypoplasia. Their predicted
and pulmonary hypertension (PH). Reduced air space survival rate is less than 20%, less if the liver is up.
and vascular bed lead to hypoxia, hypercarbia, and The rate of bronchopulmonary dysplasia (BPD)
PH.The abnormal vasculature is also more sensitive to in the (rare) survivors is greater than 75%.
pulmonary vasoconstriction, which worsens PH, further
• Fetuses with an O/E LHR between 26% and 35%
increasing the right-to-left shunt. This leads to a vicious
(irrespective of the liver position) and those with
cycle preventing gas exchange of the shunted blood in
an O/E LHR between 36% and 45% and liver up
addition to increasing acidosis and hypoxia.
have moderate hypoplasia. They have a predicted
Prenatal diagnosis survival rate around 50% (range:30%–60%). The
The cornerstone of better outcome is a bet- rate of BPD is around 30%.
ter prenatal diagnosis of the condition. Not only the • Fetuses with an O/E LHR between 36% and
diagnosis but also the staging of the disease based 45% with liver down and those with an O/E LHR
on various parameters helps in gauging prognosis of greater than 45% have mild hypoplasia and are
the baby and in extremely poor prognosis cases, fetal likely (>75%) to survive. In the latter group, the
termination may be offered. But as per current Indian rate of BPD is around 10%.
law, termination is allowed only up-to 20 weeks of
Currently MRI lung volumetry is also used as a
gestation, irrespective of the condition of fetus.
tool to predict the outcome, as a lesser lung volume
The predictors looked for in a fetal scan ante- means a worser disease.
natally are: polyhydramnios, intrathoracic stomach or
Assessment of severity of pulmonary hypoplasia
liver, abdominal circumference, lung/transverse thorax
ratio and lung-to-head ratio (LHR). • PAO2 - PaO2 > 500 mmHg breathing 100% O2 –
predicts non survival
The lung-thorax transverse area ratio (LT ratio),
is calculated by a simple ratio of right and left lung • 400-500 mmHg - survival uncertain
area to thorax area in a cardiac four-chamber view, to • <400 mmHg; has better prognosis
assess the severity of the pulmonary hypoplasia. LT
ratio of less than 0.25 indicates that the fetus has a • Cardiac catheterization, echocardiography, color
severely hypoplastic lung and requires close attention doppler, pulmonary angiography
to determine the timing of delivery. • Bohn’s index prognosticates information as ‘ven-
The currently used indicator of severity is the tilatory index’ (V.I.) :
LHR or the Lung to Head ratio. Here the ratio of the mean airway pressure X respiratory rate= V.I
contra-lateral lung volume to the head circumference
• Neonate with PaCO2 < 40 mmHg and V.I < 1000
is taken. A ratio of less than 1.4 is bad and a ratio
always survive
of less than 1.0 shows severe pulmonary hypoplasia.

• While PaCO2 > 50 mmHg, V.I <1000 or PaCO2 < • Pre-ductal SaO2 > 85%
40 mmHg, V.I > 1000 usually die.
• Ventilation off HFOV and shifted to conventional
Signs and symptoms ventilation
• Cyanosis and tachypnea • Blood pressure stabilized with minimal ino-
tropes
• Scaphoid abdomen, barrel chest, bowel sounds
heard in the chest To achieve the above a lot of hard work is needed
which starts from the moment of the delivery. In many
• Heart sounds heard on right hemithorax (apparent
centres, pre-natal diagnosis is established and the de-
dextrocardia)
livery can happen in a planned way in a higher tertiary
• Absent breath sounds on left side chest centre which can manage these cases (case load of >
• CXR confirms gas filled bowel in the left hemitho- 10 per year). A senior neonatologist should be present
rax with mediastinal shift at delivery. Normal delivery can be allowed, followed by
immediate intubation of the child. The aim at delivery
• Radio opaque dye through the nasogastric tube is to avoid the breathing / gasping of the baby as this
may delineate the bowel in the chest results in air ingestion into the stomach and bowels,
Preoperative management / optimization further worsening the oxygenation. Some centres
(Japanese) ensure a deeply sedated baby using a GA
• Assess associated anomalies for LSCS with a high dose opioid and intubating the
• Optimise oxygenation and hemodynamics, using depressed neonate.
appropriate ventilator strategies and inotropes After the initial intubation and resuscitation, the
(details below) baby is shifted to NICU, where the baby is ventilation
• Ensure normothermia using conventional ventilation. “Gentle ventilation’
protocols with minimal airway pressure, minimal or
• Correct metabolic acidosis and respiratory acido-
no muscle paralysis and with permissive hypercapnia
sis prior to surgery
and minimal sedation with fentanyl infusion reduces
• Venous access adequate sized. Neck veins barotrauma and volutrauma.
preserved for ECMO in centres were this facility
If pre-ductal SaO2 of 85% is not achieved with
is available. Umblical or femoral veins can be
100% O2 (or if peak pressures are exceeding 25 cm
used.
H2O), HFOV (High Frequency Oscillatory Ventilation)
• Use of vasodilators - tolazoline, prostacycline, is used. HFOV uses a very low tidal volume and a very
dipyridamole, nitric oxide high rate. The variable to control here is the rate (given
as Hertz) which varies from 1-5 hertz (1 hertz=60/min)
• Minimize sympathetic discharge by high dose
and the mean pressure, which should not exceed 13
opioids
cm H2O. The FiO2 is adjusted separately.
• Nasogastric suction for gastric decompression
Other advances which help in stabilizing the child
• Transport to OT with manual ventilation and ECG, include the use of ECMO (Extra Corporeal Membrane
SpO2 monitoring. Oxygenation) and Vasodilators. ECMO is an off-shoot
of a cardiac bypass mechanism. Here the patient’s
Preoperative stabilization
blood is drawn typically through a femoral artery and
It is now internationally agreed that surgical cor- oxygenated through a membrane oxygenator and re-
rection should never be an ‘emergency’. It is always turned via the umbilical or femoral vein. ECMO is used
better to stabilize the child for a few hrs to days till the in very few advanced centres of the world. There is no
following are achieved conclusive proof that ECMO has increased the survival
rates in CDH babies.

In cases of severe pulmonary hypertension, nitric The balloon is typical placed in the 26 th-28th
oxide has been used as also prostacycline etc. Nitric week and removed by the 34th week, antenatally. If
oxide is an endothelial derived relaxing factor. It is a se- emergency delivery is needed, the balloon is removed
lective pulmonary vasodilator with no effect on systemic immediately after birth.
circulation. In circulation, it is immediately inactivated
on exposure to hemoglobin. A special equipment is Anesthetic considerations
needed to deliver nitric oxide, which is usually given Most babies are shifted while on a ventilator usu-
at an inhaled concentration of 20-80 ppm. ally with arterial and central lines as well as multiple
In-utero management advances infusion pumps. Shifting can be hazardous and care
has to be taken. In the OT, the temperature is set at
Since the mid 1990s, there have been attempts
at tracheal obstruction (TO) to improve lung maturity. about 25 degrees Celcius, an overhead warmer may
In brief, the action mechanism takes advantage of a also be used. The baby is paralysed and a dose of
physiologic process through which lung growth and fentanyl 2mcg/kg is given. IPPV is with pressure con-
maturation are steered. During fetal life, the lung se- trolled mode, with a peak pressure of 20-25cm H2O.
cretes fluid, stenting the fetal airways under pressure, Inhalational agent we prefer is sevoflurane set to 1 MAC
as long as the glottis is closed. During fetal breathing, and Air/O2 mixture is used without N2O. The inotropes
the glottis opens and the pressure gradient is lev- are adjusted to achieve a mean arterial pressure of
eled. These cyclic pressure changes are essential to 40-45 mmHg.
balanced lung growth and maturation. Prenatal TO
prevents egress of lung fluid, which increases airway Monitoring
pressure, causing proliferation, increased alveolar Pulse oxymeter both above/below the nipple for
air space, and maturation of pulmonary vasculature. preductal and postductal SpO2 (the aim is to achieve
TO also has a potentially deleterious effect; when
85-90% SaO2 pre-ductal), ECG, invasive blood pres-
sustained, it reduces the number of type II cells and
sure (preferable), capnography, precordial/oesopha-
surfactant expression. This can be alleviated by in
geal stethoscope, temperature, CVP, Airway pressure,
utero release, a concept that was captured by the term
plug-unplug sequence. Tracheal occlusion was initially FiO2.
done by hysterotomy of the mother. Now, percutaneous Surgical Correction
techniques have been perfected, FETO (percutaneous
Fetoscopic Endoluminal Tracheal Occlusion) using lo- Repair of hernia is not a surgical emergency un-
cal anesthesia (see figures below). less the contents of hernia are incarcerated. As men-
tioned before a preoperative stabilization is preferred
and only a stable baby is shifted to OT, typically in 2-7
days post delivery.
Though traditionally an open (thoracotomy or
laparotomy) procedure was done, many centres are
now doing the repair thoracoscopically. This puts an
Fig 1: Balloon in the trachea, MRI Image of the same additional burden of air insufflations and further hypoxia
in some neonates. Also, maintainence of normocarbia
is a problem and acceptance of moderate hypercarbia
is safe.
At the end of the procedure, elective ventilation is
continued in NICU for a few more days till the sponta-
neous efforts of the baby improve and all parameters
become normal.
Fig 2: Schematic representation of the FETO procedure

Prognosis 3. Deprest J, Jani J, Lewi L, et al. Fetoscopic surgery:

encouraged by clinical experience and boosted by
Mortality depends on the reappearance of fetal
instrument innovation. Semin Fetal Neonatal Med
circulation due to pulmonary hypoplasia, associated
2006;11: 398–412.
congenital anomalies, inadequate pre operative prepa-
ration, pneumothorax, MODS etc. With current best 4. Jani JC, Nicolaides KH, Gratacos E, et al. Fetal
management practices (without ECMO), survival rates lung-to-head ratio in the prediction of survival in
over 70% are possible. severe left-sided diaphragmatic hernia treated by
fetal endoscopic tracheal occlusion (FETO). Am J
Even those who survive should be monitored for
Obstet Gynecol 2006;195:1646–50.
complications like pulmonary, gastric reflux, develop-
mental delays etc. 5. Gallot D, Coste K, Francannet C, et al. Antenatal
detection and impact on outcome of congenital
References and Suggested Reading
diaphragmatic hernia: a 12-year experience in
1. Deprest JA et al. Changing Perspectives on the Auvergne (France). Eur J Obstet Gynecol Reprod
Perinatal Management of Isolated Congenital Biol 2005;125:202–5.
Diaphragmatic Hernia in Europe. Clin Perinatol 36
6. Khan A, Lally K. The role of extracorporeal mem-
(2009) 329–347
brane oxygenation in the management of infants
2. King H and Booker PD. Congenital diaphragmatic with congenital diaphragmatic hernia. Semin Peri-
hernia in the neonate. Continuing Education in An- natol 2005;29:118–22.
esthesia, Critical Care & Pain | Volume 5 Number
7. Logan JW, Cotten CM, Goldberg RN, et al. Me-
5 2005
chanical ventilation strategies in the management
of congenital diaphragmatic hernia. Semin Pediatr
Surg 2007; 16:115–25.

Perioperative Management of Difficult
Airway in a Parturient 113 Arvind Palanisamy
01 PERIOPERATIVE MANAGEMENT OF DIFFICULT

AIRWAY IN A PARTURIENT
Brigham and Women’s Hospital Arvind Palanisamy
Harvard Medical School
Boston, USA
Incidence of difficult airway in pregnancy ternal coagulopathy, failed epidural/spinal anesthesia,

and perceived lack of time for a neuraxial technique
Historically, the incidence of difficult airway in
are commonly cited, and these reasons are unlikely
obstetrics is consistently cited to be approximately
to ever change. In addition, the rising incidence of
1 in 250-300 cases, a rate that is 8-fold higher than
morbid obesity in pregnancy (which makes neuraxial
in the general population.(1, 2) However other studies,
techniques highly challenging) and advanced maternal
from institutions that perform general anesthesia for
age (along with serious medical problems that might
obstetrics more frequently, report a remarkably lower
preclude a neuraxial technique) are likely to either
difficult intubation rate of approximately 1 in 1500.(3)
maintain or increase the rate of general anesthesia
Perhaps, there is some element of truth in the ad-
use. Furthermore, neuraxial techniques are not without
age, ‘Practice Makes Perfect’. So, how do we ensure
complications either. In fact, a recent closed claims
residents get adequate training in obstetric general
analysis suggests that complications secondary to
anesthesia? Should we do more emergent cesarean
neuraxial techniques during labor and delivery are on
deliveries under general anesthesia? The answers are
the rise. Taken together, obstetric general anesthesia is
complicated.
unlikely to disappear and, therefore, it is imperative that
One reason for concern is that the overall inci- residents get adequate exposure during their training.
dence of general anesthesia use in pregnancy is on So, what is it about the obstetric airway that makes it
the wane. Widespread adoption of neuraxial techniques a challenge?
for labor and delivery has caused a drastic reduction
Airway changes during pregnancy and labor
in the use of general anesthesia for cesarean delivery.
Numerous retrospective studies have suggested that Airway management in a pregnant patient can
this is the case; for example, in a single tertiary-care be challenging due to a multitude of reasons. Though
institution, the general anesthesia rates for cesarean anatomical and physiological changes of pregnancy
delivery dwindled from 7.2% to < 1% over a period are primarily responsible for the perceived difficulty,
of 15 years.(4, 5) Though this decline in general anes- the contribution of a stressful operating room environ-
thesia use is accompanied by a welcome decrease ment and sub-optimal patient positioning during an
in maternal mortality, the significant implication right emergency cesarean delivery should not be forgotten.
now is the lack of resident training in obstetric general To facilitate easy understanding, these factors can be
anesthesia. The reasons for the use of emergent gen- classified as either direct (pregnancy-related) or indirect
eral anesthesia have not changed: fetal distress, ma- (environmental) as summarized as follows.

Direct Factors Indirect Factors

Easily traumatized airway: Fluid retention and
capillary engorgement causes a highly vascular Stressful environment: The highly charged and
and friable mucosa. This can result in bleeding emotional nature of emergency cesarean delivery
and edema even after minimal airway can result in impaired judgment and erroneous
manipulation and compound the risk of a difficult decision-making.
6
airway.
Difficult laryngoscopy: Increase in the Suboptimal patient positioning: Lack of
transverse and anteroposterior diameters of the attention to patient positioning due to the
thoracic cavity increases the substernal angle emergent nature of surgery, and presence of left
from 70 to 105 degrees and causes an expanded uterine displacement and surgical drapes may
7
resting position of the thoracic cage. This, add to the perceived difficulty in airway
alongside an increase in breast tissue during management.
pregnancy, restricts laryngoscope
maneuverability.
Rapid desaturation: A combination of decreased Complexity of decision-making: Though safe
functional residual capacity (FRC) and enhanced management of the pregnant mother is of
oxygen demand places the parturient at a risk for essence, the presence of a distressed fetus adds
8
rapid desaturation during intubation apnea. another layer of complexity in the decision-making
algorithm.
Failure to recognize a changing airway class
during labor: Multiple studies have demonstrated
that labor, per se, consistently upgrades the
9, 10
Mallampatti airway classification.
Evaluation of the obstetric airway Does the airway class change further during labor and
delivery?
The most crucial element in planning an anes-
thetic technique is ‘preparation’. Alongside a thorough Airway Changes in Labor: To answer this interesting
and focused medical and obstetric history, an airway question, Kodali et al(9) used two separate methods to
examination is an integral component of preoperative assess airway changes during labor and delivery. First,
preparation. Unlike general surgical patients with ‘static’ the authors documented the traditional airway class
airways, the obstetric airway changes ‘dynamically’ pre-labor and post-delivery using standardized pho-
both during pregnancy, and more significantly, during tography in 61 parturients. The authors demonstrated
labor. a significant increase in Mallampati airway class at the
two time points. Specifically, the airway class increased
Airway changes during pregnancy: Pilkington et.
by one grade in 20 subjects (33%), and by two grades
al(11) performed a longitudinal study in 242 pregnant
in 3 subjects (5%). Strikingly, at the end of the study
women to evaluate airway changes during the course
there were 8 subjects with Class 4 airways despite
of pregnancy with 12 and 38 weeks of gestation as
starting the study with none. In the second study,
the time points for airway evaluation. Using standard-
the authors used acoustic reflectometry to document
ized photographs to document the Mallampati class,
oropharyngeal volume changes during labor and de-
the authors elegantly showed a 34% increase in the
livery in an additional 21 laboring women. There were
incidence of Class 4 airways between 12 and 38
significant decreases in oral volume, and pharyngeal
weeks, a change that was significantly correlated with
area and volume immediately after labor and delivery.
weight gain during pregnancy. These findings made
Interestingly, neither the duration of labor nor the total
the authors summarise that progressive fluid retention
volume of fluids administered seemed to correlate with
may, in part, be responsible for the changes in airway
the airway changes. Boutonnet et. al(10) extended the
class. The clinically relevant question then becomes:

study further and evaluated airway class changes in 87 rescue device after failed endotracheal intubation.13-15
pregnant women starting at the 8th month of pregnancy, Furthermore, most anesthesiologists are facile with
and re-assessed them at the time of epidural catheter LMA use and it is perhaps not surprising that the LMA
placement, 20 min after delivery, and 48 h postpartum. is incorporated into most difficult airway algorithms.
This study not only confirmed Kodali et. al’s findings When two well-directed attempts at intubation have
but also revealed that the airway changes were not failed, or if the SpO2 is < 90%, it is advisable to con-
fully reversed even at 48 h after delivery. But do these sider an extraglottic airway device such as the LMA as
airway changes during pregnancy increase the difficulty early as possible. Though an LMA with an esophageal
of intubation in the obstetric patient? conduit such as LMA Proseal is theoretically preferred,
attempts to obtain it should not delay airway manage-
Usefulness of Mallampati classification in obstet-
ment – a classic LMA is probably just as good. A few
rics: Basaranoglu et. al(12) attempted to answer this
caveats need to be kept in mind when placing an
question by analyzing five predictors of difficult intuba-
LMA after unsuccessful intubation attempts: transient
tion (Mallampati airway class, sternomental distance,
release of cricoid pressure to ensure optimal seating of
thyromental distance, interincisor gap, atlantoocciptal
the cuff, ensuring a deep plane of anesthesia because
extension) in 239 pregnant women at the time of
considerable time may have elapsed since administra-
emergency cesarean delivery. The same anesthe-
tion of the intravenous induction agent, and ensuring
siologist completed these measurements as well as
that the airway is clear of blood from traumatic intuba-
the subsequent laryngoscopy grading. Using logistic
tion attempts. Failure to recognize these factors may
regression analysis, the authors showed that no single
result in severe laryngospasm and a ‘Cannot Intubate,
test, including Mallampati class, or a combination of
Cannot Ventilate’ (CICV) situation necessitating a sur-
tests had an acceptable positive predictive value. Also,
gical airway.
these authors predict that 79% of all difficult intubations
will be missed using these assessment tools. Though Role of video laryngoscopes
thought provoking, this study suffers from investiga-
Video laryngoscopes (VL) provide unparalleled
tor bias in that the same anesthesiologist made all
visualization of the glottis, superior illumination, and a
the measurements. In addition, it is unclear how long
favorable viewing angle as the line-of-sight is close to
these patients labored for, and how these elaborate
the tip of the laryngoscope.(16) Specifically, video laryn-
measurements were made in the setting of emergent
goscopes have been shown to enhance Cormack and
general anesthesia. Nevertheless, this study behooves
Lehane laryngeal grades both in simulators as well as
us to search for other possible predictors of difficult
in live subjects. Though promising, it is unclear if the
intubation in pregnancy.
use of VL decreases the incidence of difficult intubation.
Role of airway adjuncts In fact, numerous case series and randomized studies
report enhanced laryngoscopy views but do not clearly
Securing the airway with a cuffed endotracheal
show a decrease in difficult intubation. These studies
tube is often considered the gold standard for manage-
notwithstanding, video laryngoscopes offer a viable
ment of a pregnant airway during cesarean delivery.
alternative to direct laryngoscopy in patients with a dif-
Though ideal, one should not lose sight of the forest
ficult airway. But, how useful are they in the pregnant
for the trees. The underlying principle of managing a
patient?
pregnant airway is to prevent hypoxia by all means
possible, and this entails placement of any device that Despite the burgeoning popularity of VL devices
facilitates air exchange. in difficult airway management, there are no published
randomized studies to support its use in pregnancy.
Among airway rescue devices, the laryngeal
Given the emergent nature of obstetric general anes-
mask airway (LMA) remains the most widely studied.
thesia, it is unlikely that randomized, controlled trials
It has been successfully used as a primary anesthetic
will ever be performed. However, taking cues from their
technique in elective cesarean deliveries and as a

successful use in the management of difficult airway in assigned a direct laryngoscopy grade. Sequentially,
morbidly obese patients, it seems reasonable to use the monitor was switched on to ascertain the video
these devices in obstetric anesthesia. In fact, Dhonneur laryngoscopy grade. In this small case series, almost all
et. al(17) reported the successful use of the Airtraq VL in patients with conventional laryngoscopy grades 2 and
the management of difficult intubation in two morbidly 3 became grade 1 after conversion to video laryngos-
obese women. Furthermore, an unpublished study copy, confirming that VL offers superior visualization
from the United Kingdom demonstrated enhancement even in obstetric patients. At our institution, we routinely
of laryngeal grades with a video laryngoscope in 27 use VL (with or without a bougie) for management of the
pregnant women undergoing general anesthesia for potentially difficult airway in the parturient. Moreover,
cesarean delivery.(18) Following induction of general if general anesthesia is warranted in any case, we
anesthesia, the anesthetist attempted intubation with a encourage the residents to use a VL to get acquainted
video laryngoscope (with the monitor switched off) and with a potentially useful fallback technique.
Algorithm for the Anticipated Difficult Airway 19

Algorithm for the unanticipated difficult airway (20)

REFERENCES 11. Pilkington S, Carli F, Dakin M J, et al. Increase in Mal-

lampati score during pregnancy. Br J Anaesth 1995;
1. Barnardo P D, Jenkins J G. Failed tracheal intubation in
74: 638-642.
obstetrics: a 6-year review in a UK region. Anesthesia
2000; 55: 690-694. 12. Basaranoglu G, Columb M, Lyons G. Failure to predict
difficult tracheal intubation for emergency caesarean
2. Samsoon G L, Young J R. Difficult tracheal intubation:
section. Eur J Anaesthesiol; 27: 947-949.
a retrospective study. Anesthesia 1987; 42: 487-490.
13. Han T H, Brimacombe J, Lee E J, Yang H S. The
3. Rocke D A, Murray W B, Rout C C, Gouws E. Relative
laryngeal mask airway is effective (and probably safe)
risk analysis of factors associated with difficult intuba-
in selected healthy parturients for elective Cesarean
tion in obstetric anesthesia. Anesthesiology 1992; 77:
section: a prospective study of 1067 cases. Can J
67-73.
Anaesth 2001; 48: 1117-1121.
4. Tsen L C, Pitner R, Camann W R. General anesthesia
14. Keller C, Brimacombe J, Lirk P, Puhringer F. Failed
for cesarean section at a tertiary care hospital 1990-
obstetric tracheal intubation and postoperative respira-
1995: indications and implications. Int J Obstet Anesth
tory support with the ProSeal laryngeal mask airway.
1998; 7: 147-152.
Anesth Analg 2004; 98: 1467-1470, table of contents.
5. Palanisamy A, Mitani A A, Tsen L C. General anes-
15. Halaseh B K, Sukkar Z F, Hassan L H, Sia A T, Bushnaq
thesia for cesarean delivery at a tertiary care hospital
W A, Adarbeh H. The use of ProSeal laryngeal mask
from 2000 to 2005: a retrospective analysis and 10-year
airway in caesarean section--experience in 3000 cases.
update. Int J Obstet Anesth; 20: 10-16.
Anaesth Intensive Care; 38: 1023-1028.
6. Munnur U, de Boisblanc B, Suresh M S. Airway prob-
16. Niforopoulou P, Pantazopoulos I, Demestiha T, Koud-
lems in pregnancy. Crit Care Med 2005; 33: S259-
ouna E, Xanthos T. Video-laryngoscopes in the adult
268.
airway management: a topical review of the literature.
7. Thomson K J, Cohen M E. Studies on the circulation Acta Anaesthesiol Scand; 54: 1050-1061.
in pregnancy II. Vital Capacity observations in normal
17. Dhonneur G, Ndoko S, Amathieu R, Housseini L E,
pregnant women. . Surg Gynecol Obstet 1938; 66:
Poncelet C, Tual L. Tracheal intubation using the Airtraq
591-603.
in morbid obese patients undergoing emergency cesar-
8. Alaily A B, Carrol K B. Pulmonary ventilation in preg- ean delivery. Anesthesiology 2007; 106: 629-630.
nancy. Br J Obstet Gynaecol 1978; 85: 518-524.
18. Gray K, Lucas N, Robinson P N, Loughman B. A case
9. Kodali B S, Chandrasekhar S, Bulich L N, Topulos G series of successful videolaryngoscopic intubations
P, Datta S. Airway changes during labor and delivery. in obstetric patients. O 13. Jersey, UK: OAA Annual
Anesthesiology 2008; 108: 357-362. Meeting Abstract, 2009.
10. Boutonnet M, Faitot V, Katz A, Salomon L, Keita H. Mal- 19. Kuczkowski K M, Reisner L S, Benumof J L. Airway
lampati class changes during pregnancy, labour, and problems and new solutions for the obstetric patient. J
after delivery: can these be predicted? Br J Anaesth; Clin Anesth 2003; 15: 552-563.
104: 67-70.
20. Mhyre J M, Healy D. The unanticipated difficult intuba-
tion in obstetrics. Anesth Analg; 112: 648-652.

FOCUS SESSIONS


PDPH – Prevention and Management 121 Venkatesh S
01 PDPH – PREVENTION AND MANAGEMENT
Associate Professor, Venkatesh S

Srmc, Chennai.
History mater have contested this classical description of the

anatomy of the duramater. These studies describe the
In August 1898, Karl August Bier, a German
dura mater as consisting of collagen fibres arranged
surgeon first described the symptoms associated with
in several layers parallel to the surface. Each layer or
postdural puncture headache. Bier surmised that the
lamellae consists of both collagen and elastic fibres
headache was attributable to loss of CSF. By the early
that do not demonstrate specific orientation. The outer
1900s, there were numerous reports in the medical
or epidural surface may indeed have dural fibres ar-
literature of the application of spinal anesthesia using
ranged in a longitudinal direction, but this pattern is not
large spinal needles. Headache was reported to be
repeated through successive dural layers. Recent mea-
a complication in 50% of subjects. At that time, the
surements of dural thickness have also demonstrated
headache was believed to resolve within 24 h.
that the posterior dura varies in thickness, and that the
In 1951, Whitacre and Hart developed the pencil- thickness of the dura at a particular spinal level is not
point needle. Developments in needle design since that predictable within an individual or between individuals.
time have led to a significant reduction in the incidence Dural perforation in a thick area of dura may be less
of post-dural puncture headache. However, dural punc- likely to lead to a CSF leak than a perforation in a thin
ture headache still remains a disabling complication of area, and may explain the unpredictable consequences
needle insertion into the subarachnoid space. of a dural perforation.
Pathophysiology of dural puncture Cerebrospinal fluid
Anatomy of the spinal dura mater CSF production occurs mainly in the choroid
The spinal dura mater is a tube extending from plexus, but there is some evidence of extrachoroidal
the foramen magnum to the second segment of the production. About 500 ml of CSF is produced daily (0.35
sacrum. It contains the spinal cord and nerve roots ml/min). The CSF volume in the adult is approximately
that pierce it. The duramater is a dense, connective 150 ml, of which half is within the cranial cavity. The
tissue layer made up of collagen and elastic fibres. The CSF pressure in the lumbar region in the horizontal
classical description of the spinal dura mater is of col- position is between 5 and 15 cm H2O. On assuming
lagen fibres running in a longitudinal direction. Clinical the erect posture, this increases to over 40 cm H2O.
teaching based upon this view of the dura recommends The pressure of the CSF in children rises with age, and
that a cutting spinal needle be orientated parallel rather may be little more than a few cm H2O in early life.
than at right angles to these longitudinal dural fibres. Duramater and response to trauma
Orientating the needle at right angles to the parallel
The consequences of perforation of the spinal or
fibres, it was said would cut more fibres. The cut dural
cranial dura are that there will be leakage of CSF. Neu-
fibres, previously under tension, would then tend to
rosurgical experience of dural perforation is that even
retract and increase the longitudinal dimensions of the
minor perforations need to be closed, either directly or
dural perforation, increasing the likelihood of a post
through the application of synthetic or biological dural
spinal headache. Clinical studies had confirmed that
graft material. Failure to close the dural perforation may
post dural puncture headache was more likely when
lead to adhesions, continuing CSF leak, and the risk of
the cutting spinal needle was orientated perpendicular
infection. Experimental studies shows that deliberate
to the direction of the dural fibres. However, recent
dural defects in the cranial dura of dogs took approxi-
light and electron microscopic studies of human dura

mately one week to close. The closure was facilitated CSF, and intracranial blood is constant. The conse-
through fibroblastic proliferation from surrounding quence of a decrease in CSF volume is a compensatory
tissue and blood clot. The study also noted that dural increase in blood volume. The venodilatation is then
repair was promoted by damage to the pia arachnoid, responsible for the headache.
the underlying brain and the presence of blood clot.
Incidence
It is therefore possible that a spinal needle carefully
placed in the subarachnoid space does not promote It is related to the size and design of the spinal
dural healing, as trauma to adjacent tissue is minimal. needle used, the experience of the personnel perform-
Indeed, the observation that blood promotes dural ing the dural puncture, and the age and sex of the
healing agrees with Gormley’s original observation patient.
that bloody taps were less likely to lead to a post-dural Needle quality
puncture headache as a consequence of a persistent
Reducing the size of the spinal needle has made
CSF leak.
a significant impact on the incidence of post-spinal
Needle tip deformation and dural perforation headache. The incidence is ~ 40% with a 22G needle;
It has been proposed that contact with bone dur- 25% with a 25G needle; 2%-12% with a 26G Quincke
ing insertion may lead to spinal needle tip deformation. needle; and < 2% with a 29G needle. However, techni-
Damaged needle tips could lead to an increase in the cal difficulties leading to failure of the spinal anaesthetic
size of the subsequent dural perforation. Recent in vivo are common with needles of 29G or smaller. In 1951,
studies have demonstrated that the cutting type spinal Whitacre and Hart introduced the atraumatic spinal
needle is more likely to be deformed after bony contact needle. This design offered the handling characteristics
than comparable sized pencil-point needles. of larger needles with a low incidence of post-spinal
headache. Needle modifications since that time, such
Consequences of dural puncture
as the Sprotte and Atraucan needles, promise further
Puncture of the dura has the potential to allow reductions in post spinal headache.
the development of excessive leakage of CSF. Excess
Diagnostic lumbar puncture
loss of CSF leads to demonstrable reduction in CSF
volume. After the development of post dural puncture The acceptance of small gauge needles for diag-
headache, the presence of a CSF leak has been con- nostic lumbar puncture has been slow to develop
firmed with radionuclide cisternography, radionuclide Neurologists still believe that adequate flow of
myelography, manometric studies, epiduroscopy and CSF can only be achieved with spinal needles of 22G
direct visualization at laminectomy. The adult suba- or greater.
rachnoid pressure of 5-15 cm H2O is reduced to 4.0
Obstetrics
cm H2O or less. The rate of CSF loss through the dural
perforation is generally greater than the rate of CSF The parturient is at particular risk of dural punc-
production (0.35 ml/min), particularly with needle sizes ture and the subsequent headache because of their
larger than 25G. Although the loss of CSF and lowering sex, young age, and the widespread application of
of CSF pressure is not disputed, the actual mechanism epidural anesthesia. In parturients receiving epidural
producing the headache is unclear. There are two pos- anesthesia, the incidence of dural puncture is between
sible explanations. First, the lowering of CSF pressure 0 and 2.6%. The incidence is inversely related to the
causes traction on the intracranial structures in the experience of the anesthesiologist, and is said to be
upright position. These structures are pain sensitive, reduced by orientation of the needle bevel parallel to
leading to the characteristic headache. Secondly, the the dural fibres. Loss of resistance to air confers a
loss of CSF produces a compensatory venodilatation higher risk of dural puncture than loss of resistance to
(Monro-Kellie doctrine). The Monro-Kellie doctrine, or fluid. After a dural puncture with a 16G Tuohy needle,
hypothesis, states that the sum of volumes of the brain, up to 70% of subjects will report symptoms related

to low CSF pressure. Despite the high incidence of Quincke type is the standard needle with a medium
headache consequent upon dural puncture with a cutting bevel and the orifice at the needle tip. In 1926,
Tuohy needle, the anesthesiologist needs to consider Greene proposed a needle tip design with a non-cutting
a differential diagnosis, as intracranial haematoma, or edge that would separate the dural fibres to avoid post-
tumour presenting with similar symptoms to, or in as- dural puncture headache. In 1951, the Whitacre needle
sociation with, a post-dural puncture headache have was introduced and, in 1987, the Sprotte needle. The
been described. generic term for these needles is pencil-point or atrau-
Children matic, though in truth they are neither. The Whitacre
needle has a diamond shaped tip, and the Sprotte
Post dural puncture headache is reported as
needle tip is conical. The orifice is up to 0.5 mm from
uncommon in children. Although low CSF pressure or
the needle tip. Clinical and laboratory studies have
other physiological differences have been proffered as
confirmed that pencil-point needles produce fewer post
reasons to explain the low incidence in children, it is
dural puncture headaches than medium bevel cutting
likely that a low reporting rate is the explanation.
needles. However, there are disadvantages. Paresthe-
Prevention sia has been observed with the pencil-point needles.
Spinal needles have undergone numerous modi- The reason may lie in the distance from the tip of the
fications in recent years, the aim being to reduce the needle to the orifice. The tip has to be passed at least
incidence of dural puncture headache. The principal 0.5 mm into the subarachnoid space before the orifice
factor responsible for the development of a dural enters the subarachnoid space. The tip then has the op-
puncture headache is the size of the dural perforation. portunity to impinge upon the stretched cauda equina.
Other factors such as the shape of the dural perforation Giving credence to this hypothesis, paresthesia is un-
and the orientation of the spinal needle have a less common with the short bevel needles or the Atraucan
significant role. needle. The problem of low CSF flow and paresthesia
Needle size seen with the pencil-point needles has promoted the
search for novel needle designs. The Atraucan has
Large spinal needles will clearly produce large
recently been marketed. It has an orifice at the tip of
dural perforations where the likelihood of a dural
the needle. The Atraucan has a narrow cutting tip and
puncture headache is high. Conversely, the smaller
an atraumatic bevel. Initial reports of these needles
needles produce small dural perforations with a lower
are promising as regards ease of use and low dural
incidence of headache. Fine gauge spinal needles, 29G
puncture headache rate.
or smaller, are technically more difficult to use, and for
spinal anesthesia at least, are associated with a high Operator skill level and fatigue
failure rate. A balance has to be struck between the
It has been suggested that the incidence of in-
risks of dural puncture headache and technical failure.
advertent dural puncture during epidural anesthesia
25G, 26G and 27G needles probably represent the
is inversely related to operator experience. However,
optimum needle size for spinal anesthesia.
sleep deprivation, operator fatigue and the effect of
Needle orientation night work may be a confounding variable producing
There are many clinical, and laboratory, studies the higher incidence of inadvertent dural puncture in
that lend credence to the hypothesis that perpendicular junior personnel performing epidural analgesia.
orientation of the bevel of a spinal or epidural needle Presentation of dural puncture headache
leads to a reduction in the incidence of post-dural
puncture headache. Onset
Needle design Headache and backache are the dominant symp-

toms that develop after accidental dural puncture.
Over the years since Quincke and Bier, a large
Ninety per cent of headaches will occur within 3 days
number of needle designs have been introduced. The
of the procedure, and 66% start within the first 48 h.

Rarely, the headache develops between 5 and 14 days and brain stem; obliteration of the basilar cisterns; and
after the procedure. Headache may present immedi- enlargement of the pituitary gland. CT myelography,
ately after dural puncture. However, this is rare, and retrograde radionuclide myelography, cisternography,
its occurrence should alert the physician to alternative or thin section MRI can be used to locate the spinal
causes. source of the CSF leak.
Symptoms Differential diagnosis
Headache is the predominant, but not ubiquitous The diagnosis of post-dural puncture headache is
presenting complaint. The headache is described as frequently clear from the history of dural puncture and
severe, searing and spreading like hot metal. The com- the presence of a severe postural headache. How-
mon distribution is over the frontal and occipital areas ever, it is important to consider alternative diagnosis
radiating to the neck and shoulders. The temporal, as serious intracranial pathology may masquerade
vertex and nuchal areas are reported less commonly as as a post dural puncture headache. Clinicians should
the site of discomfort, although neck stiffness may be remember that intracranial hypotension can lead to
present. The pain is exacerbated by head movement, intracranial hemorrhage through tearing of bridging
and adoption of the upright posture, and relieved by dural veins, and a delay in diagnosis and treatment
lying down. An increase in severity of the headache can be dangerous. Diagnoses that may masquerade
on standing is the sine qua non of post-dural puncture as post dural puncture headache include intracranial
headache. Other symptoms associated with dural tumours, intracranial haematoma, pituitary apoplexy,
puncture headache include nausea, vomiting, hearing cerebral venous thrombosis, migraine, chemical or
loss,tinnitus, vertigo, dizziness and paresthesia of the infective meningitis, and nonspecific headache. It
scalp, upper and lower limb pain. Visual disturbances has been estimated that 39% of parturients report
such as diplopia or cortical blindness have been re- symptoms of a headache unrelated to dural puncture
ported. Cranial nerve palsies are not uncommon. Two following delivery. The largest follow-up of post-dural
cases of thoracic back pain without headache have puncture headache is still that of Vandam and Dripps
been described. Neurological symptoms may precede in 1956.They reported that 72% of headaches resolved
the onset of grand mal seizures. Intracranial subdural within 7 days, and 87% had resolved in 6 months. The
haematomas, cerebral herniation and death, have duration of the headache has remained unchanged
been described as a consequence of dural puncture. since that reported in 1956. In a minority of patients
Unless a headache with postural features is present, the headache can persist. Indeed, case reports have
the diagnosis of post-dural puncture headache should described the persistence of headache for as long as
be questioned, as other serious intracranial causes for 1-8 yr after dural puncture. It is interesting to note that
headache must be excluded. even post-dural puncture headaches of this duration
have been successfully treated with an epidural blood
Diagnosis
patch.
The history of accidental or deliberate dural
Treatment
puncture and symptoms of a postural headache, neck
ache and the presence of neurological signs, usually Overview
guide the diagnosis. Where there is doubt regarding the
The literature regarding the treatment of post-
diagnosis of post dural puncture headache, additional
dural puncture headache often involves small numbers
tests may confirm the clinical findings. A diagnostic
of patients, or uses inappropriate statistical analysis.
lumbar puncture may demonstrate a low CSF opening
Studies observing the effects of treatments in post-dural
pressure or a `dry tap’, a slightly raised CSF protein,
puncture headache often fail to recognize that, with no
and a rise in CSF lymphocyte count. An MRI may
treatment, over 85% of postdural puncture headaches
demonstrate: diffuse dural enhancement, with evidence
will resolve within 6 weeks.
of a sagging brain; descent of the brain, optic chiasm,

Psychological puncture site; and (iii) control the cerebral vasodilata-

tion.
It is important both from a clinical and medico-legal
point of view, to discuss the possibility of headache A number of therapeutic agents have been sug-
before a procedure is undertaken that has a risk of this gested for the management of post-dural puncture
complication. Even so, this discussion will not prepare headache. The main problem in choosing the most
the patient for the sensations he or she feels should the appropriate one is the lack of large, randomized, con-
headache develop. Obstetric patients are particularly trolled clinical trials.
unfortunate should they develop this complication, as
they expect to feel well and happy and to be able to look DDAVP, ACTH
after their new baby. It is important to give the mother a A report in 1964 identified 49 methods for treating
thorough explanation of the reason for the headache, post spinal headache. There appears to be no limit to
the expected time course, and the therapeutic options the imagination of physicians in treatments offered for
available.
post spinal headache. However, there is a lack of sta-
Simple tistical data to support their ideas. Regarding DDAVP
Bed rest has been shown to be of no benefit. (desmopressin acetate), intramuscular administration
Supportive therapy such as rehydration, acetamino- before lumbar puncture was not shown to reduce the
phen, non-steroidal anti-inflammatory drugs, opioids, incidence of post dural puncture headache. ACTH (ad-
and anti-emetics may control the symptoms and so renocorticotrophic hormone) has been administered as
reduce the need for more aggressive therapy, but do an infusion, but inadequate statistical analysis prevents
not provide complete relief. assessment of the value of ACTH.
Posture Caffeine
If a patient develops a headache, they should be Caffeine is a central nervous system stimulant
encouraged to lie in a comfortable position. The patient that amongst other properties produces cerebral vaso-
will often have identified this, without the intervention constriction. It is available in an oral and i.v. form. The
of an anesthesiologist. There is no clinical evidence oral form is well absorbed with peak levels reached in
to support the maintenance of the supine position 30 min. Caffeine crosses the blood brain barrier and
before or after the onset of the headache as a means the long half-life of 3-7.5 h allows for infrequent dos-
of treatment. The prone position has been advocated, ing schedules. The most frequently quoted work on
but it is not a comfortable position for the post-partum
the treatment of post dural puncture headache with
patient. The prone position raises the intra abdominal
caffeine is that of Sechzer. He evaluated the effects of
pressure, which is transmitted to the epidural space and
one or two 0.5 g doses of i.v. caffeine on subjects with
may alleviate the headache. A clinical trial of the prone
established post-dural puncture headache. There are
position following dural puncture failed to demonstrate
some statistical and methodological flaws in this study,
a reduction in post dural puncture headache.
but it was concluded that i.v. caffeine is an effective
Abdominal binder therapy for post-dural puncture headache.
A tight abdominal binder raises the intra-abdomi- Dose
nal pressure. The elevated intra-abdominal pressure is
transmitted to the epidural space and may relieve the The dose now recommended for the treatment of
headache. Unfortunately, tight binders are uncomfort- post-dural puncture headache is 300-500 mg of oral
able and are seldom used in current practice. There or i.v. caffeine once or twice daily. One cup of coffee
are few units that would recommend this approach. contains about 50-100 mg of caffeine and soft drinks
contain 35-50 mg. The LD50 for caffeine is of the order
Pharmacological treatment
of 150 mg/kg. However, therapeutic doses have been
The aim of management of post-dural puncture associated with central nervous system toxicity, and
headache is to: (i) replace the lost CSF; (ii) seal the atrial fibrillation.

Mode of action patch as the standard against which to evaluate alterna-

tive methods to treat post-dural puncture headache.
It is assumed that caffeine acts through vaso-
constriction of dilated cerebral vessels. If cerebral Technique
vasodilatation were the source of the pain, cerebral
The presence of fever, infection on the back,
vasoconstriction might limit the pain experienced. In-
coagulopathy, or patient refusal are contraindications
deed, it has been demonstrated that caffeine causes
to the performance of an epidural blood patch. As
a reduction in cerebral blood flow, but this effect is not
a precautionary measure, a sample of the subject’s
sustained. Caffeine therapy is simple to administer
blood should be sent to microbiology for culture. With
compared with the technical skills required to perform
the patient in the lateral position, the epidural space
an epidural blood patch. Were caffeine as successful
is located with a Tuohy needle at the level of the sup-
as suggested by previous reports, it would no doubt
posed dural puncture or an intervertebral space lower.
be widely advocated. However, a North American
The operator should be prepared for the presence of
hospital survey of the treatment of post-dural puncture
CSF within the epidural space. Up to 30 ml of blood is
headache identified that most hospital practitioners had
then taken from the patient’s arm and injecting slowly
abandoned the use of caffeine as they had found it
through the Tuohy needle. Should the patient describe
ineffective. The effects of caffeine on post-dural punc-
lancinating pain of dermatomal origin the procedure
ture headache seem, at best, temporary. In addition,
must be stopped. There is no consensus as to the
caffeine is not a therapy without complications, and
precise volume of blood required. Most practitioners
does not restore normal CSF dynamics, thus leaving
now recognise that the 2 to 3 ml of blood originally
the patient at risk from the serious complications as-
described by Gormley is inadequate, and that 20-30
sociated with low CSF pressure.
ml of blood is more likely to guarantee success. Larger
Sumatriptan volumes, up to 60ml,have been used successfully in
cases of spontaneous intracranial hypotension. At the
The treatment for migranous headaches has
conclusion of the procedure, the patient is asked to lie
focused on modification of cerebral vascular tone.
still for one or, preferably, 2 h, and is then allowed to
Sumatriptan is a 5-HT1D receptor agonist that promotes
walk.
cerebral vasoconstriction, in a similar way to caffeine.
Sumatriptan is advocated for the management of mi- Contraindications include those that normally ap-
graine and recently, for post-dural puncture headache. ply to epidurals, but include a raised white cell count,
There have been only a few case reports where su- pyrexia and technical difficulties. Limited experience
matriptan was used successfully to manage post-dural with HIV- positive patients suggest that it is acceptable
puncture headache. However, a recent controlled trial providing no other bacterial or viral illnesses are ac-
found no evidence of benefit from Sumatriptan for tive. Epidural blood patch following diagnostic lumbar
the conservative management of post-dural puncture puncture in the oncology patient raises the potential
headache. for seeding the neuroaxis with neoplastic cells. One
case has been reported of a successful patch without
Epidural blood patch
complications, and one case where the risks of central
History nervous system (CNS) seeding of leukaemia were con-
After the observation that `bloody taps’ were as- sidered to outweigh the benefits of an epidural blood
sociated with a reduced headache rate, the concept of patch.
the epidural blood patch has developed. The theory is The blood patch
that the blood, once introduced into the epidural space,
Using either radiolabelled red cells or an MRI
will clot and occlude the perforation, preventing further
scan, several studies have reported the degree of
CSF leak. The high success rate and the low incidence
spread of the epidural blood patch. After injection, blood
of complications have established the epidural blood
is distributed caudally and cephalad regardless of the

direction of the bevel of the Tuohy needle. The blood blood patch, a large retrospective study over a 12-year
also passes circumferentially around to the anterior period found that subsequent epidural analgesia was
epidural space. The thecal space is compressed and successful in >96% of patients. Prophylactic epidural
displaced by the blood. In addition, the blood passes blood patch in parturients, where the incidence of post-
out of the intervertebral foramina and into the paraver- dural puncture headache is high is an attractive option.
tebral space. The mean spread of 14 ml of blood is six Prophylactic patching has generally been dismissed as
spinal segments cephalad and three segments caudad. ineffective, but the evidence is conflicting. A controlled
Compression of the thecal space for the first 3 h, and trial in post-myelogram headaches, and one after spi-
a presumed elevation of subarachnoid pressure, may nal anesthesia and after unintentional dural puncture
explain the rapid resolution of the headache. Com- with an epidural needle, have confirmed the benefit
pression of the thecal sac is not, however, sustained of prophylactic patching. Those studies that have not
and maintenance of the therapeutic effect is likely to supported the use of prophylactic patching may have
be attributable to the presence of the clot eliminating used insufficient blood for the patch. The pressure
the CSF leak. It has been observed that CSF acts as gradient between the thecal and epidural space may be
a procoagulant, accelerating the clotting process. At high immediately after dural puncture and lead to patch
7-13 hours, there is clot resolution leaving a thick layer separation from the site of the perforation. Blood patch-
of mature clot over the dorsal part of the thecal sac. ing at that time may therefore need a greater volume
Animal studies have demonstrated that 7 days after of blood to produce a successful patch compared with
the administration of an epidural blood patch, there is a late patch, where the CSF pressure may be lower.
widespread fibroblastic activity and collagen formation.
Chronic headache
Fortunately, the presence of blood does not initiate
an inflammatory process and there is no evidence of Patients may present with features of a post-spinal
axonal edema, necrosis or demyelination. headache never having received an epidural or spinal
injection. A report of six such cases, with headaches
Outcome
that had been present between 1 and 20 yr, showed
The technique has a success rate of 70-98% if complete relief of headache following lumbar epidural
carried out more than 24 h after the dural puncture. If blood patch. It is interesting to speculate that these
an epidural blood patch fails to resolve the headache, headaches may have been attributable to unidentified
repeating the blood patch has a similar success rate. spontaneous intracranial hypotension.
Failure of the second patch and repeating the patch
Epidural saline
for a third or fourth time has been reported. However,
in the presence of persistent severe headache, an Concerns have been expressed about the poten-
alternative cause should be considered. tial danger of an autologous epidural blood patch for
the treatment of post-dural puncture headache. The
Complications
immediate resolution of the headache with a blood
Immediate exacerbation of symptoms and radicu- patch is attributable to thecal compression raising the
lar pain have been described. These symptoms do not CSF pressure. An epidural injection of saline would,
persist and resolve with the administration of simple in theory, produce the same mass effect, and restore
painkillers. Long term complications of epidural blood normal CSF dynamics. As saline is a relatively inert
patch are rare. A single case report of an inadvertent and sterile solution, epidural saline bolus or infusion
subdural epidural blood patch described non-postural, appears to be an attractive alternative. Regimens
persistent headache and lower extremity discomfort. that have been advocated include: (i) 1.0-1.5 litre of
The issue of the effect of the blood patch on the suc- epidural Hartmann’s solution over 24 h, starting on
cess of subsequent epidurals has been addressed the first day after dural puncture; (ii) up to 35 ml/hr of
in few studies. Though case reports describe limited epidural saline or Hartmann’s solution for 24-48 h, or
spread of epidural analgesia after previous epidural after development of the headache; (iii) a single 30 ml

bolus of epidural saline after development of headache response that would promote the healing process. The
and (iv) 10-120 ml of saline injected as a bolus via the evidence for the administration of epidural dextran to
caudal epidural space. treat post-dural puncture headache is not proven and
the theoretical argument to justify its use is poor.
Advocates of an epidural saline bolus or infusion
maintain that the lumbar injection of saline raises epi- Epidural, intrathecal and parenteral opioids
dural and intrathecal pressure. Reduction in the leak
A number of authors have advocated the use
would allow the dura to repair. However, observations
of epidural, intrathecal or parenteral morphine; the
of the pressures produced in the subarachnoid and epi-
majority of these reports are either case reports or in-
dural space show that, despite a large rise in epidural
adequately controlled trials. Some of the studies used
pressure, the consequent rise in subarachnoid pres-
epidural morphine after the onset of headache, others
sure maintains the differential pressure across the dura.
used epidural or intrathecal morphine as prophylaxis or
The pressure rise is also not sustained and is dissipated
in combination with an intrathecal catheter. A controlled
within 10 min. The saline may induce an inflammatory
trial of intrathecal fentanyl as prophylaxis found no
reaction within the epidural space, promoting closure
evidence of a reduction in the incidence of post-spinal
of the dural perforation. Histological studies have not
headache after dural puncture with a 25-gauge spinal
demonstrated an inflammatory response following epi-
needle.
dural dextran 40 administration. There is no reason to
suppose that epidural saline is more likely to accelerate Fibrin glue
dural healing through a pro-inflammatory action than Alternative agents to blood, such as fibrinous glue,
dextran 40. Thus, there are no studies that are able to have been proposed to repair spinal dural perforations.
demonstrate either a sustained rise in CSF pressure Cranial dural perforations are frequently repaired suc-
or accelerated closure of the dural perforation after the cessfully with it. In the case of lumbar dural perforation,
administration of epidural saline. the fibrin glue may be placed blindly or using CT-guided
Whilst there are many case reports describing percutaneous injection. There is, however, a risk of
the success of epidural saline, comparative trials with the development of aseptic meningitis with this proce-
epidural blood patches have not demonstrated the long- dure.
term efficacy of epidural saline placement. It is difficult Intrathecal catheters
to conclude from the evidence therefore, that epidural
After accidental dural perforation with a Tuohy
saline administration will restore normal CSF dynamics.
needle, it has been suggested that placement of a
The administration of large volumes of epidural saline
spinal catheter through the perforation may provoke an
may result in intraocular haemorrhages through a pre-
inflammatory reaction that will seal the hole. Evidence
cipitous rise in intracranial pressure. Epidural dextran,
to support this claim is conflicting. The mean age of the
despite the paucity of evidence to support epidural
patients in some of the trials has been >50 yr, where
saline, some observers have considered the epidural
the rate of post-dural puncture headache is low. Some
administration of dextran 40. Those studies that recom-
trials have used spinal micro-catheters, 26G-32G; oth-
mend dextran 40, either as an infusion or as a bolus,
ers have placed 20G epidural catheters through an 18G
conclude that the high molecular weight and viscosity
Tuohy needle. Histopathological studies in animals and
of dextran 40 slows its removal from the epidural space.
humans with long-term intrathecal catheters confirm
The sustained tamponade around the dural perforation
the presence of an inflammatory reaction at the site
allows spontaneous closure. However, it is unlikely that
of the catheter. Comparison between the effects of
dextran 40 will act any differently to saline in the epidu-
a catheter left in situ for 24 h and for several days or
ral space. Any pressure rise within the subarachnoid
weeks would seem inappropriate. If, after accidental
space would, like saline, be only transient. Histological
dural puncture with a Tuohy needle, the insertion of an
inspection of the epidural space after administration of
intrathecal catheter reduced the post-dural puncture
dextran 40, does not demonstrate any inflammatory

headache rate, then it would be worth considering. reasoning. Gormley’s observation that bloody taps
However, neurological complications, such as cauda were less likely to give rise to headaches, though prob-
equina syndrome and infection, should preclude the ably incorrect, has led to the widespread application of
use of intrathecal catheters. blood patching for the treatment of post-dural puncture
headache. The benefit of prophylactic blood patching is
Surgery
not so clear but deserves consideration in those most
There are case reports of persistent CSF leaks, at risk from a headache, such as the parturient,and
that are unresponsive to other therapies, being treated after accidental dural perforation with a Tuohy needle.
successfully by surgical closure of the dural perforation. There are occasions when blood patches appear to
This is clearly a last resort treatment. be ineffective in treating the headache. It is wise to
Conclusion consider other causes of the headache before applying
alternative therapeutic options.
Post-dural puncture headache is a complication
that should not to be treated lightly. There is the po- References
tential for considerable morbidity, even death. In the • Miller’s anesthesia-7th edition
majority of cases, the problem will resolve spontane-
• Chestnut’s textbook of obstetric Anesthesia-3rd edi-
ously. In some patients, the headache lasts for months
tion
or even years. Therapies that have been offered have
not always arisen through the application of logic or • British Journal of Anesthesia-91 (5): 718±29 (2003)

Monitoring Depth of Anesthesia 130 Manjushree Ray
01 MONITORING DEPTH OF ANESTHESIA
Institute of Postgraduate Medical Education Manjushree Ray

& Research
Kolkata
Anesthesia is a state of drug induced uncon- though electrophysiological studies have shown that
sciousness in which patient neither perceives nor muscle relaxant do affect the depth of anesthesia
recalls noxious stimulation. Depth of anesthesia is probably by inhibiting the projection of sensory input to
defined as drug induced probability of non response CNS. Awareness during anesthesia is defined as post
to a stimulus calibrated against strength of stimulus operative recall of events occurring under general an-
and the difficulty in suppressing response. American esthesia. Incidence is about 0.1 - 0.2 % in general non
Society of Anesthesiologists Task Force in a review high risk surgery(2). The risk increases in emergency
on ‘Practice Advisory for Intraoperative Awareness surgery, cardiac surgery, intra operative hypotension-
and Brain Function Monitoring(1) defined depth of shock, and caesarean section. Despite a variety of
anesthesia or depth of hypnosis as a continuum of available monitoring methods, awareness is difficult to
progressive central nervous system depression and recognize while it is occurring in intra operative period.
decreased responsiveness to stimulation. Components No intra operative monitoring system has 100% sen-
of depth of anesthesia are analgesia, hypnosis, amne- sitivity and specificity. The consensus to detect intra
sia and blockade of autonomic response. Interesting to operative awareness is to interview the patient in post
note that muscle relaxation which is an integral part of operative period with Modified Brice questionnaire.
general anesthesia has nothing to do with the depth,
Methods of monitoring of intra operative awareness
Subjective method Objective method

A: Clinical parameters A: Lower esophageal contractility
x Autonomic response (LOC)
x Somatic response B: Heart rate variability (HRV)
B: Isolated forearmtechnique C: Electrophysiological based monitor
x Spontaneous EEG
x Processed EEG Parameters
Median Frequency (MF)
Spectral Edge Frequency (SEF)
Bis-spectral Index (BIS)
x EMG Study
x Mid Latency Auditory Evoked
Response(MLAER)
x Narcotrend
x SNAP II, Patients State index (PSI),
Cerebral State Monitor (CSM)
x Entropy
D: Functional Near Infrared Spectroscopy
E: Position Emission Tomography
F: Ultrasensitive Super conductive Quantum
Interference Device (SQUIDS)

Subjective parameters of intra operative monitoring Patient movement

of depth of anesthesia
It is one of the commonest monitor to detect ad-
A) Clinical criteria: equacy of anesthesia.
Autonomic response: For volatile anesthetic agents, it is predicted by

MAC. MAC-awake < MAC-incision < MAC -intubation<
1. Hemodynamic parameters: blood pressure and MAC-BAR. In unstimulated patients both explicit and
heart rate implicit memory may be absent at end-tidal concentra-
tion of inhalational agents equal to MAC-awake. During
2. ECG change: degree of respiratory sinus arrhyth- induction with intra venous agents, the clinical end point
mia. of hypnotic dose is guided by -
3. Pupil size. • Loss of verbal responsiveness,
4. Respiratory: rate and depth of tidal volume • Loss of eyelid reflex,
5. Other autonomic responses like sweating, tearing, • Loss of corneal reflex,

salivation, flushing. • Absence of movement in response to squeezing
Somatic response: the trapezius muscle.
Body movements, swallowing, coughing, grimac- But as they possess a little analgesic properties,
ing or opening of eyes. the intravenous anesthetic agents cannot eliminate
movement in response to surgical noxious stimulus.
Patient response to surgical stimulus (PRST) scoring system
Index Condition Score

Systolic Blood Pressure (P) < Control + 15 0
< Control + 30 1
> Control + 30 2
Heart Rate (R) < Control + 15 0
< Control + 30 1
> Control + 30 2
Sweating (S) Nil 0
Skin moist 1
Visible beads of sweat 2
Tear (T) No excess tear in open eye 0
Excess tear in open eyes 1
Tear over flowing 2
Limitations of Clinical methods response not only involve CNS but is also medi-
ated by spinothalamic tract and adrenal medullary
• Patient movement does not represent the effect of
reflex spinal arc. During organ harvesting from
anesthetic in CNS, as the main site of anesthetic
brain dead patients, hemodynamic response
induced inhibition of motor response to noxious
have shown to have occurred in response to skin
stimulus is spinal cord not brain. Opioids strongly
incision.
inhibit movement during anesthesia, though they
have little role in preventing awareness when used Isolated forearm technique (IFT)
as single agent even in high dose.
A purposeful movement in response to verbal
• Autonomic responses are nonspecific and they command indicates light anesthesia. In this method
may be modified by pharmacodynamic interaction a tourniquet is placed on an arm of the patient before
of other various anesthetic and non anesthetic administration of a muscle relaxant and inflated above
drugs. It is assumed that hemodynamic stress systolic pressure to exclude its effect. The arm is there-

fore free to move during anesthesia. Ischemia has to that the anesthetic agents either directly or indirectly
be prevented by periodically releasing the tourniquet, first act on the brain stem and then probably inhibit the
usually before topping up the muscle relaxant. Patient cerebral cortex via ascending efferent projections from
may then be asked to move his fingers to check ad- the midbrain. The special analysis of HRV revealed 3
equacy of depth of anesthesia. components: 1) Low frequency fluctuations; believed
to be circadian. 2) Medium frequency fluctuations; at-
Limitations
tributed to baroreceptor reflex. 3) High frequency fluc-
1) Non specific startle response may be interpreted tuations. Various studies have shown that the level of
as consciousness. respiratory sinus arrhythmia (RSA) reflects the level of
2) The levels of anesthesia needed to prevent anesthetic depth. Reduction in RSA during anesthesia,
movements in patients using IFT are significantly together with increase in RSA during recovery. In addi-
higher than those routinely used, since the advent tion, surgical stimulation during light anesthesia elicits
of muscle relaxant. a greater increase on RSA than seen during lightening
anesthesia alone.
3) Patients have reported that they heard commands
to move the isolated arm, but were unable to do Electrophysiological approach to monitor ad-
so, even though nerve stimulator suggested that equacy of anesthesia
the arm was not paralyzed. • Spontaneous EEG
4) It does not predict wakefulness reliably. • Various processed EEG like Median frequency(MF),
5) Arm cannot be torniqueted more than 20 min. Spectral edge frequency(SEF), Bis spectral index
(BIS)
Objective parameters of intra operative monitoring
of depth of anesthesia – • EMG study
Lower esophageal contractility (LOC) • Brain stem evoked responses most useful
of which is median latency auditory evoked
The non-striated muscles in the lower half of
response(MLAER).
esophagus retain non-propulsive spontaneous con-
tractions, mediated via vagal motor nuclei and reticular • Narcotrend
activating system in the brain stem and this activity • SNAP II, Patient state index (PSI), Cerebral state
can be seen even after full skeletal muscle paralysis monitor (CSM),
by neuromuscular blocking agents. Measurements of
• Entropy – State entropy and response entropy
LOC therefore, provide two prime derivatives.
Spontaneous EEG
Spontaneous lower esophageal contractions
(SLOC): The frequency of these movements is in- It is a noninvasive monitor of cerebral activity in
creased as the dose of the anesthetic is reduced. unconscious patient and is related to cerebral blood
flow and metabolism.
Provoked lower esophageal contractions: pulsatile
response to brief inflation of small balloon at distal part Common rationale: Anesthetic depth modifies
of esophagus. Amplitude of response decreases as spontaneous cortical EEG changes towards slowing,
depth of anesthesia increases. synchronization and loss of randomness. But, the raw
EEG is difficult to interpret for its complexity in signal.
Limitation: The response is nonspecific and is bet-
Almost all anesthetic drugs have some effect on EEG
ter predictor of movement to noxious stimulus than
pattern but the effects are not identical. Besides many
awareness.
other variables, such as temperature and carbon
Heart rate variability (HRV): dioxide tension, affect interpretation of the electroen-
Recent research using animal models have shown cephalogram.

Processed EEG functions

Raw EEG signal are digitalised and processed
using a mathematical technique called Fourier analy-
sis and power spectrum is calculated from individual
component. As for MF and SEF, their utility as a moni-
tor to detect a particular state of anesthesia is limited.
In some study, they were found to be associated with
opioid requirement during general anesthesia.
Bis spectral index
It is a FDA approved EEG based monitoring sys-
tem to detect anesthetic depth.
It assesses the hypnotic component of anesthesia.
Mechanism
Display parameters in BIS monitor:
It is a statistical system to analyse EEG and com-
pute an index ranging from 0 to 100 to quantify level of The BIS reading: A processed numeric value that cor-
CNS depression where 0 is an isoelectric EEG and 100 relates with the level of hypnosis. It is derived from the
is fully awake state. The main variables incorporated preceding 15 to 30 seconds of EEG measurements.
in the algorithm are The range is 0 (flat line EEG) to 100 (awake).
1) Frequency and power spectrum of the EEG, SQI: The signal quality (S/Q) index indicates the quality
of the EEG signal and is primarily based on impedance
2) The amount of burst suppression, and
and artefact.
3) The degree of synchronization of the EEG.
EMG: The electromyograph (EMG) indicator displays
The EEG was processed by removing high and power from muscles in decibels in the frequency range
low frequency artefacts, electrocardiographic signals, of 70 to 110 Hz. The range is 30 to 55 dB.
pacemaker spikes, eye blinks, wandering baseline, and
EEG: The EEG display presents a filtered EEG wave-
interference by alternating current. The EEG data were
form shown in trend graph.
then analyzed by three different approaches: Fourier
spectral analysis, bispectral analysis, and time domain SR: Suppression ratio displays the percentage that an
analysis. Time domain analysis was used to character- isoelectric (flat line) condition exists over the prior 63
ize burst suppression (seen at a BIS value of less than seconds. The range is 0% to 100%. At BIS index val-
40) and isoelectricity.The EEG was smoothed across ues below 40, the index is determined primarily by the
the power spectrum and bispectrum by using a mov- degree of ‘‘suppression’’ or isoelectricity of the EEG.
ing average. The analysis then examined the degree Burst Count number: (when a BIS Extend Sensor
of beta or high frequency (14 to 30 Hz), the amount is in use).
of low-frequency synchronization, and the presence
Anesthetic drugs and BIS score
of fully or nearly suppressed periods (i.e. isoelectric
signal). The algorithm to determine the relative weight- Commonly used hypnotics such as midazolam,
ing in the final calculation of the BIS value (0 to 100) propofol, isoflurane, sevoflurane, and desflurane re-
involved performing a multivariate statistical analysis. duces BIS value in predictable manner when admin-
The monitor uses a sensor to transmit EEG signals from istered systematically for induction and maintenance
the patient to a digital signal converter, which digitizes of anesthesia. And this decrease correlates well with
the signal and sends it to the monitor for processing clinical sedation grading scale such as MOAA/S(3).
and analysis

Halothane at equipotent doses results in higher • Better hemohodynamic profile in intra operative
BIS values than isoflurane or sevoflurane. Transient period
paradoxical response to increased isoflurane has been
• Better and early recovery(8)
reported. Studies suggest that nitrous oxide given in
concentrations of up to 70% has minimal effect on the • Drug cost.
BIS. The dissociative anesthetic ketamine produces • Some studies it is found to be directly related to
excitatory effects on the EEG. Ketamine doses that increased long term mortality(9)
create unresponsiveness (0.25 to 0.5 mg/kg) did not
BIS index values correlate to the reduction in ce-
change the BIS. Etomidate is associated with increased
rebral metabolic rate measured from positron emission
muscle activity upon induction and thus may falsely
tomographic scanning during administration of hypnotic
elevate BIS. Studies have demonstrated an effect of
drugs(10). The BIS correlates well with the level of the
muscle relaxants in deepening depth of anesthesia.
responsiveness (responsiveness scores of modified
The most bizarre was the study by Messner and as-
observer’s assessment of alertness/sedation level).
sociates, in which awake volunteers (the investigators
themselves) received succinylcholine with no hypnotic Pitfalls and caveats
and the BIS decreased.(4) Reversal of muscle relaxation
• Conditions associated with spuriously high BIS
can also change the amount of EMG activity and influ-
value – spontaneous EMG activity, electrical ar-
ence the monitor. Beta blocker such as esmolol can
tefacts like, electro cautary, artificial pacemaker,
also alter the BIS in some studies. BIS is not affected
electrical equipments, high impedence due to
by low dose of opioids, so the target BIS needs to be
poor contact ,
selected based on anesthetic technique. Thus, in the
absence of opioids or analgesics, BIS should be 25 to • Conditions associated with spuriously low BIS
35; with the use of opioid or analgesic supplementation, value – cerebral ischemia or hypo perfusion,
BIS can be 45 to 60. drugs (esmolol, epinephrine, muscle relaxants
like pancuronium or),elderly.
BIS interpretation
• N2O upto 70% conc, ketamine, xenon has no
Recall of words or pictures is depressed at BIS
effect on BIS.
values of 70 to 75. Explicit recall is significantly dimin-
ished as BIS decreases below 70, and a BIS of 40 to • It is much a measure of hypnotic component
60 correlates with general anesthesia rather to predict movement in response to pain.
Clinical utility Pediatric depth of anesthesia monitoring
• Prevention of awareness: BIS maintained within The normal EEG in children differs significantly
a range of 40 to 60, there is a consistent 80% from the adult EEG and undergoes age-related chang-
reduction in the occurrence of awareness both es during development. From infancy to adulthood the
in general and high risk populations(5). amplitude of the EEG decreases and the frequency
spectrum shifts to higher frequencies. But the conven-
• The BIS monitor, designed to measure the hyp-
tional BIS monitors are claimed to represent the depth
notic component of an anesthetic regimen, has
of anesthesia for children as young as 1 year of age,
been shown to predict loss of consciousness and
when pediatric sets are used.
movement in response to surgical skin incision
and loss of recall with good probability under Bispectral Index Monitoring in Critical Care
certain clinical conditions(6) Bispectral index (BIS) monitoring is new to critical
• Drug titration: BIS index (keeping around 50) is care. Until recently, sedation has been assessed indi-
found to reduce hypnotic drug consumption by rectly, primarily by using vital signs and less commonly
20–30%(7) by using subjective sedation scales. Because of the

limitations of these subjective assessment tools, over now being used in critical care. Optimizing the assess-
sedation and under sedation remain major challenges ment and management of sedation and analgesia, BIS
to critical care setting. The BIS, an objective measure monitors provide information clinically relevant to the
of sedation traditionally used in general anesthesia, is adjustment of dosages of sedating medications.
Over Sedation Under Sedation

x Patient unable to participate in x Anxiety, agitation
care x Ĺ Costs, nursing time
x Delayed weaning x Ĺ Use of neuromuscular blocking
x Ventilator associated pneumonia agents
x Ĺ Unnecessary testing x Ĺ Risk of recall/ awareness
x Ĺ ICU & hospital stay x Unpleasant events
x Ĺ Costs x Ĺ Unintended medical device
removal
Use of a BIS monitor reduces cost of sedation and Other recently developed monitors used to detect
decreases the frequency of over sedation in the ICU. intra operative sedation
In the Critical Care setting, the BIS Monitor is com- Narcotrend

monly used to allow objective assessment of sedation
The Narcotrend (MonitorTechnik, Bad Bramstedt,
during:
Germany) is an EEG monitor designed to measure
• Mechanical ventilation • Barbiturate coma • Bedside the depth of anesthesia. It has been developed at the
procedures • Neuromuscular blockade. University Medical School of Hannover, Germany,
has been commercially available for 5 years and has
In some studies, BIS, could not be validated as a
meanwhile received US Food and Drug Administration
tool suitable for monitoring sedation in a heterogeneous
approval(12). The Narcotrend algorithm is based on
group of surgical ICU patients(11). BIS values should be
pattern recognition of the raw electroencephalogram
interpreted cautiously in patients with known neurologi-
(EEG) and classifies the EEG traces into different
cal disorders, in those taking psychoactive medica-
stages: A (awake), B (Sedated), C (light anesthesia)
tions and in children less than 1 year old. A reduction
D ( General anesthesia) E (General anesthesia with
in cerebral blood flow or cerebral oxygen supply may
deep sedation) and F( GA with burst suppression).
result in a reduced BIS value. Patients with unilateral
The Narcotrend stages D or E are assumed equivalent
brain injuries may manifest asymmetric BIS values.
to BIS values between 64 and 40 indicating general
Preliminary research suggests that BIS values may
anesthesia(13). Multiple clinical and validation studies
be lower on the injured side. Natural sleep cycles may
are available for the Narcotrend monitor, including
affect the hypnotic level. In the REM sleep pattern, the
comparisons with the BIS monitor (Aspect Medical
low amplitude / high frequency EEG patterns may be
Systems, Natick, USA).
similar to those in the awake state, but with co-existing
hypotonia and eyeball movement artefacts. Entropy
Seizure related EEG is typically comprised of Entropy was originally defined as a physical con-
higher frequency activity that can increase the BIS cept related to the amount of disorder in a system. In
value. Presence of pacemaker may alter BIS falsely. measuring depth of anesthesia, it is another method
Currently, reliance on the BIS alone for sedative man- of interpreting complex EEG and EMG pattern. Three
agement is not recommended. sensors attached to the patients head provide electro-
encephalography (EEG) and frontal electromyogram

(FEMG) readings which are analysed to produce a measured independently and continuously. These
score of 0-100 for response entropy (RE: response to metrics have been correlated with neural activity by
stimuli), a score of 0-91 for state entropy (SE: depth numerous studies and provide a map of cognitive func-
of sedation) and 0-100% for burst suppression indication (an optical topograph). Assessment for depth of
tion (an isolectric state). A regular signal where the anesthesia is based on ongoing studies in measuring
wavelength and amplitude are constant over time, level of brain activation of patients under anesthesia in
would have a low entropy value and a signal with an response to stimuli such as sensory effects in operating
irregular wavelength and amplitude, a higher entropy room, pain, pharmacological agents, etc.
value. The lower the patient’s entropy value, the more
Position emission tomography (PET)
sedated they are.
It has been used in limited studies. PET scanning
Auditory evoked response
revealed that propofol anesthesia has a widespread
The early cortical (mid latency) auditory evoked suppressive effect on cerebral metabolism.(14). This
response appears to be the most promising evoked approach may lead to the adoption of a standard, ab-
response as a monitor of depth of anesthesia. Both solute scale of anesthetic depth; against which other
inhaled and intravenous anesthetics affect auditory- measures can be calibrated. However, it is an invasive
evoked potentials in a similar and dose-dependent method and cannot be used in routine cases.
manner. The typical AEP response to increasing
Ultra sensitive super conducting quantum interfer-
anesthetic concentrations is increased latency and
ence device (SQUIDS)
decreased amplitude of the various waveform compo-
nents. Muscle relaxants do not affect auditory evoked It is a non-invasive method, which measures
responses. functional activity of brain. Although expensive at
present, this may provide the ultimate monitor to the
Similar to BIS, auditory evoked potentials pro-
anesthesiologists. It is capable of determining not just
duces the A-Line Autoregressive Index (AAI), which is
anesthetic depth but also awareness, anoxia, ischemia
scaled from 0 to 100. Surgical anesthesia is suggested
and unusual pathology.
when AAI is in the range of 15 to 25.
Acknowledgement : I Sincerely thank Dr. Suvadip Sen
Surface electromyography
for his help in preparation of this lecture notes.
The frontalis muscle has been chosen because of
References:
its innervations by visceral efferent fibres of the facial
nerve and its lesser sensitivity to the effects of muscle 1. Practice Advisory for Intraoperative Awareness and
relaxants. Tonic activity decreases during induction Brain Function Monitoring. A Report by the American
of anesthesia and increases with emergence. So, it is Society of Anesthesiologists Task Force on Intraopera-
more likely to represent patient movement in response tive Awareness. Anesthesiology 2006; 104:847–64.
to inadequate analgesia. However, electromyography 2. Sebel PS, Bowdle TA, Ghoneim MM, Rampil IJ, Padilla
values vary widely among patients. RE, Gan TJ, Domino KB: The incidence of awareness
Functional near infrared spectroscopy during anesthesia: A multicenter United States study.
Anesth Analg 2004; 99:833–9.
Functional near-infrared (fNIR) technology re-
lies on optical techniques derived from the physical 3. Glass PS, Bloom M, Kearse L, Rosow C, Sebel P,
principles of light absorption and reflectance to detect Manberg P. Bispectral analysis measures sedation
changes in the hemodynamic response of the cortex and memory effects of propofol, midazolam, isoflurane,
to brain activation. fNIR uses near infrared spectros- and alfentanil in health volunteers. Anesthesiology.
copy to continuously track hemodynamic and thereby 1997;86: 836-47.
metabolic changes in the brain. Oxygenated and de- 4. M. Messner, U. Beese, J. Romstöck, M. Dinkel, and
oxygenated hemoglobin levels of cerebral blood are K. Tschaikowsky. The bispectral index declines during

neuromuscular block in fully awake persons. Anesth 15.

Analg. 2003; 97:488-91.
9. Cohen NH. Anesthetic depth is not (yet) a predictor of
5. PS Myles, K Leslie, J McNeil, A Forbes, MTV Chan. mortality! Anesth Analg. 2005 Jan;100(1):1-3.
Bispectral index monitoring to prevent awareness dur-
10. Bowdle TA. Depth of Anesthesia Monitoring; Anesthe-
ing anesthesia: the B-Aware randomised controlled
siol Clin. 2006 Dec;24(4):793-822.
trial. Lancet. 2004;363:1757-1763
11. Frenzel D, Greim CA, Sommer C, Bauerle K, Roewer
6. Sebel PS, Lang E, Rampil IJ, White PF, Cork R,
N. Is the bispectral index appropriate for monitoring the
Jopling M, Smith NT, Glass PS, and Manberg P. A
sedation level of mechanically ventilated surgical ICU
multicenter study of bispectral electroencephalogram
patients? Intensive Care Med. 2002;28:178–183
analysis for monitoring anesthetic effect. Anesth Analg.
1997;84:891-9. 12. 10. Kreuer S, Wilhelm W. The Narcotrend monitor. Best
Pract Res Clin Anaesthesiol. 2006 Mar;20(1):111-9.
7. Kelly SC. “clinical application for BIS monitoring.” In
monitoring level of consciousness during anesthesia 13. 11. Kreuer S, Biedler A, Larsen R, Schoth S, Altmann
& sedation: a clinical guide to the Bispectral index. S, Wilhelm W. The Narcotrend--a new EEG moni-
Newton: Aspect medical system, 2003. tor designed to measure the depth of anesthesia. A
comparison with bispectral index monitoring during
8. Gan TJ, Glass PS, Windsor A, Payne F, Rosow C,
propofol-remifentanil-anesthesia. Anaesthesist. 2001
Sebel P, Manberg P. Bispectral index monitoring allows
Dec;50(12):921-5.
faster emergence and improved recovery from propo-
fol, alfentanil, and nitrous oxide anesthesia. BIS Utility 14. Alkire MT, Barker SJ, Haier RJ, et al. A position emis-
Study Group. Anesthesiology. 1997 Oct;87(4):808- sion tomography study of cerebral metabolism in a
volunteer during propofol anest

Management of ARDS - What works? 138 Renuka M K
01 MANAGEMENT OF ARDS - WHAT WORKS?
Assistant Professor, Renuka M K

SRMC, Chennai
Acute lung injury (ALI)/acute respiratory distress Ventilator induced lung injury (VILI)
syndrome (ARDS) represent the most severe form
Several types of lung injury are associated with
of pulmonary organ dysfunction driven by systemic
mechanical ventilation. High levels of inspired oxygen
inflammation, with a significant increase in morbidity can cause oxidant injury in the airways and lung
and mortality. parenchyma of animals, and oxygen toxicity is a
Essentially all patients with acute lung injury (ALI) concern in humans. The toxic threshold is still debated
or acute respiratory distress syndrome (ARDS) require and may be variable depending on many factors, in-
mechanical ventilatory assistance to support gas ex- cluding pre existing lung disease that may offer some
change and reduce the work of breathing associated protection. High alveolar oxygen concentrations can
with the lung impairment. Clinicians are sometimes also result in absorption atelectasis. It is generally
challenged to maintain acceptable gas exchange desirable to reduce fraction of inspired oxygen (FiO2)
to below 0.60, and it is assumed that FiO2 of 0.40
while avoiding harmful mechanical ventilation prac-
can be safely tolerated for extended periods, but FiO2
tices. Unfortunately, this life-sustaining support may
should be reduced to the lowest level that maintains
actually cause further lung damage and possibly lead
acceptable oxygenation. In patients with ARDS, other
to increased mortality. However many lung protective
triggers of VILI are likely more important in causing
strategies have been proposed after complete evalu-
pulmonary damage.
ation of the patient.
Gross extra-alveolar air (barotrauma) is associ-
Initial evaluation
ated with high ventilating pressure and alveolar over-
Patients with severe ARDS are at high risk for distension, although it can occur at modest pressures in
death and should be identified using a lung injury the presence of pre-existing lung injury. This air can find
score of 3 and evaluated for an underlying cause its way to the pleural space and subcutaneous tissue,
of ALI (especially sepsis, pneumonia, pancreatitis, as well as to the mediastinal, pericardial, and vascular
transfusion associated lung injury) and treated prompt- spaces. The incidence of barotrauma appears to be
ly. This evaluation includes a meticulous examination low when alveolar inflation pressures are kept below
to look for occult sources of sepsis (e.g., deep soft 35 cm H2O.
tissue infections) and appropriate diagnostic testing The parenchymal lung injury and gas distribution
(e.g., sterile samples for microbiological culture). If an associated with ALI/ARDS is heterogenic in nature.
underlying cause is not identified, then an alternative Using computed tomography of the chest, Gat-
diagnosis (e.g., diffuse alveolar hemorrhage) should tinoni and colleagues described three general lung
be considered, because some of these diagnoses “regions”: a region of normal lung tissue, primarily
can be treated with immunosuppressive agents. This in the nondependent areas; a region of densely con-
evaluation may require invasive diagnostic testing. In solidated, fluid-filled, or atelectatic tissue, primarily in
addition, it may be helpful to perform transthoracic or the dependent areas; and a region that is collapsed
trans-esophageal echocardiography to evaluate right during expiration but recruitable during inspiration. In
and left ventricular function, cardiac filling pressures, severe ARDS, the healthy lung areas that receive most
and the presence or absence of right heart failure and of the tidal ventilation may be reduced to one-third of
a patent foramen ovale. normal or more, resulting in the term “baby lung” to
describe the adult ARDS lung.

The mammalian lung is maximally inflated to As pressure continues to be applied the slope of
total lung capacity at a transpulmonary pressure of the inflation curve becomes steeper, suggesting better
30 to 35 cm H2O. Animal studies have demonstrated compliance and easier inflation. When the lung is near
that regional over inflation can result in a stretch injury maximal inflation, the slope of the curve becomes flat-
(volutrauma), which does not manifest as an air leak ter, suggesting the end of tidal recruitment and then
but rather as diffuse alveolar damage, similar to what overdistension. For a given pressure, the lung is at a
is seen in ARDS. This injury is most likely to occur in higher volume on deflation than it was during inflation.
the normal lung regions, as delivered volume goes to This volume difference (hysteresis) is to a large degree
the area of least resistance and elastance. Injury can dependent on surfactant function, the degree of lung
also occur when lung units are allowed to repeatedly impairment, and recruitability; less hysteresis is seen
open and collapse with tidal ventilation (atelectrauma). with more normal function and/or less recruitment po-
Both volutrauma and atelectrauma can trigger release tential. Two goals and management strategies during
of inflammatory mediators and bacterial translocation, mechanical ventilation are to (1) avoid overdistending
which may incite end-organ failure (biotrauma) and lung units by limiting the inflation volume and pres-
possibly increased mortality. sure, and (2) avoid repetitive opening and collapse
by applying adequate positive end expiratory pressure
Lung protective ventilation
(PEEP). Ideally, ventilation would take place in a “zone
Protecting the lung from injury is a balancing act of safety” on the deflation limb of the PV curve. The
between opening and maintaining the patency of as challenge is how to accomplish this.
many lung units as possible to support oxygenation
Initial ventilatory support in ALI/ARDS
while ventilating (stretching) the lung units as gently as
possible to support carbon dioxide removal and blood It is generally accepted that the primary ventilator
pH balance. strategy for patients with ALI/ARDS should be the one
reported in 2000 by the National Institutes of Health
Fig. 1 shows the inflation and deflation pressure-volume
ARDS Network, which to date is the only ventilator-
(PV) relationship of an ARDS lung. Initially modest
related therapy showing a benefit regarding mortal-
pressure is required to overcome the critical opening
ity.
pressure of lung units and allow volume to inflate the
lung. Tidal volume (VT) is targeted to 6 mL/kg of predict-
ed body weight (PBW). Volume-controlled ventilation
(VCV) in the continuous mandatory ventilation (assist-
control) mode was used in the study and is generally
recommended, but pressure control ventilation (PCV)
can be used provided VT is monitored and maintained
at approximately 6 mL/kg PBW.
End-inspiratory plateau pressure (Pplat) should
be maintained at 30 cm H2O or less. If necessary, VT
is reduced as low as 4 mL/kg with a commensurate
increase in rate, up to a maximum of 35 breaths/min.
The set rate is adjusted to maintain a ventilation pH
goal of 7.30 to 7.45, but care is taken to minimize
auto-PEEP.
Initially a FiO2 of 1.0 and PEEP of 8 to 12 cm H2O
Fig1. Pressure-volume curve derived from a patient are used, and then adjusted subsequently. Oxygen-
with ARDS. FRC, functional residual capacity; LIP, ation targets are a partial pressure of oxygen (PaO2)
lower inflection point; UIP, upper inflection point. of 55 to 80 mm Hg or oxygen saturation (SpO2) of

88% to 95%. The Pplat threshold of 30 cm H2O can PEEP i s s e t a s per the ARDSnet tables, while
be exceeded if: (1) FiO2 is 1.0 and VT is 4 mL/kg, to some clinicians prefer to individualize the PEEP titra-
allow further increases in PEEP, and (2) pH is less than tion. It appears that for patients with less severe lung
7.15 despite buffering, to allow a larger VT.VT can also injury the low-PEEP table from the ARDSnet study
be increased as high as 8 mL/kg to address ventilator is most appropriate. In patients with severe ARDS and
asynchrony, provided Pplat is below threshold; other- refractory hypoxemia, either the higher-PEEP table or
wise sedation is considered. individualizing the PEEP to respiratory mechanics may
be beneficial.
Refractory hypoxemia
Lower PEEP, Higher FiO2 Table
Some patients remain hypoxemic despite this ini-
tial management strategy. Depending on the degree of FiO2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
blood gas derangement, clinicians try alternative strat- PEEP 5 5 -8 8-10 10 10-14 14 14-18 1824
egies rather than wait. In addition to increasing FiO2,
the ventilator response to hypoxemia is generally to Higher PEEP, Lower FiO2 Table
increase mean airway pressure (Pmean) by increasing FiO2 0.3 0.4 0.5 0.5 –0.8 0.8 0.9 1.0
PEEP, lengthening inspiratory time (with an inspiratory PEEP 5 -14 14-16 16 -18 20-22 22 22 22-24
pause in volume control ventilation or preferably directly
using PCV), and increasing ventilating pressure. Es- Recruitment maneuvers and high PEEP
tablishing an adequate PEEP level should be the first
A recruitment maneuver (RM) and high PEEP
step, because minimizing atelectrauma should be as
intend t o aerate.
high a priority as improving oxygenation.
Collapsed and hooded alveoli, which may im-
PEEP
prove oxygenation, decrease ventilator induced lung
There have been 5 recent meta-analyses attempt- injury from the shear stress of repetitive opening and
ing to determine whether a high- PEEP strategy has closing of alveoli, and improve respiratory system
better outcomes than a low-PEEP strategy. None of compliance in some patients. To do so, recruitment
these studies reported a mortality difference. maneuvers use brief periods in which airway pressures
Individualized PEEP approaches include pres- are elevated and sustained at levels that are higher
sure volume loops, esophageal balloon manometry, than those that result from tidal ventilation.
and the stress index. Many ventilators have the ability High airway pressures may subject noncollapsed
to perform a slow- flow (<10 L/min constant flow) or a l v e o l i to overinflation, decreased alveolar fluid
pressure-step change PV loop to assess lower (LIP) clearance, and additional ventilator-associated lung
and upper (UIP) inflection points on the inspiratory injury or may cause hemodynamic compromise.
limb of the curve. It has been suggested that PEEP be
RM with high PEEP or high PEEP alone should
set to 2 cm H2O above LIP and that inflation pressure
be considered early in the management o f severe
remain below UIP. PV loop is influenced by increased
ARDS with life-threatening h y p o x e m i a if plateau
pleural and abdominal pressure (i.e., altered chest wall
airway pressures are 30 cm H2O. RMs is not conducted
compliance). Although evidence of improved outcome
in patients who are in shock, who have pneumotho-
is lacking, there is much interest in using esophageal
rax, or in those with focal disease. Adequate volume
pressure (Pes) manometry to calculate transpulmonary
resuscitation and sedation s h o u l d b e g i v e n to
pressure (Ptp = Palv - Pes) at end-exhalation to set
ensure patient–ventilator synchrony. It is important to
PEEP, as well as at end-inspiration to provide a ratio-
assess for improvement in oxygenation and compliance
nale for using higher than recommended plateau pres-
immediately after the intervention and again within
sures. The stress index uses the shape of the ventilator
6 to 12 hrs. If there i s no improvement, then do
pressure-time waveform, during constant inspiratory
not repeat RM. Also, abort the procedure if worsened
flow, to reflect tidal recruitment and overdistension.

hypoxemia or hypotension develops. If dead-space recruitment and improve oxygenation. Ventilation is

ventilation increases after the RM, then this suggests achieved with an oscillating piston that creates cycles
alveolar overdistension; therefore, the PEEP should be of pressure above and below the mean airway pres-
decreased. sure at a high frequency (180 –900/min), resulting in
small tidal volumes (between 1 and 2.5 mL/kg).
A recent systematic review analyzed 40 studies
that evaluated RMs. The sustained inflation method Several small retrospective studies of HFOV
(ie, continuous positive airway pressure [CPAP] of in patients with ARDS and severe hypoxemia and/
35–50 cm H2O for 20–40 seconds) was used most or elevated plateau airway pressures have revealed
often (45%), followed by high pressure control (23%), significant improvements in oxygenation and suggested
incremental PEEP (20%), and a high VT/sigh that early initiation may be associated with better out-
(10%). Oxygenation was significantly increased after comes, especially in pediatric patients.
an RM (106 vs 193 mm Hg) but was generally short
Potential disadvantages are hemodynamic dete-
lived.
rioration, barotraumas, or the need for heavy seda-
Current evidence suggests that that RMs should tion and neuromuscular blockade to reduce ventilator
not be routinely used on all ARDS patients unless asynchrony. In a large clinical trial, HFOV was not
severe hypoxemia persists. RMs might be used as a associated with more frequent episodes of intractable
rescue maneuver to overcome severe hypoxemia, to hypotension, air leak, or mucous plugging.
open the lung when setting PEEP, or following evidence
HFOV is recommended early in the course of
of acute lung derecruitment such as a ventilator circuit
severe ARDS for patients with severe hypoxemia and/
disconnect.
or elevated plateau airway pressures. HFOV should
Prone positioning not be used in patients with shock, severe airway
Prone positioning can promote recruitment of obstruction, intracranial hemorrhage, or refractory
dependent, atelectatic lung regions most affected by barotraumas; it must be used cautiously with severe
ALI/ ARDS by relieving external compressive forces, acidosis, because CO2 excretion may be limited.
thus improving ventilation- perfusion matching Partial liquid ventilation
without subjecting lungs to high airway pressures.
Partial liquid ventilation (PLV) with perfluorocar-
Although prone positioning has failed to demon- bons which was proposed as a method to open lung
strate a survival benefit in hundreds of patients enrolled units has gone out of vogue as it was associated with
in four randomized, clinical trials, the two trials that more complications like pneumothorax, hypoxia and
placed patients prone for 20 hrs per day did report hypertensive episodes.
beneficial trends in mortality rate.
Strategy for refractory cases
Data from randomized trials reveal infrequent
local complications (e.g., facial edema, conjunctival Extracorporeal life support (ECLS)
hemorrhage, and pressure ulcers) and those attribut- ECLS for severe ALI/ARDS uses a veno-venous
able to turning (e.g., dislodging of catheters and life-support circuit that removes blood from the patient
endotracheal and thoracostomy tubes). and circulates it through a membrane oxygenator to
Placing patients prone for a total of at least 20 hrs relieve the lungs from their main function of gas
per day seems to be associated with greater benefit; exchange and allow the lungs to heal. In general,
however, intermittent change the supine position there a r e two types of ECLS that h a v e been used
may be necessary for nursing care and procedures. to manage ARDS: extracorporeal membrane o x y -
g e n a t i o n (ECMO), a high-flow extracorporeal
High-frequency oscillatory ventilation membrane-oxygenation circuit, and extracorporeal
High-frequency oscillatory ventilation (HFOV) carbon dioxide removal, a low-flow, mostly extra-
uses high mean airway pressure to achieve lung corporeal CO2 removal circuit.

The use of ECLS is associated with significant hypoproteinemic patients with lung injury, though data
risks, mostly because of the need for anticoagulation on outcomes is still lacking.
and large indwelling vascular access. Commonly
When considering how to translate the results of
reported complications include clots in circuit, hemor-
the FACTT into clinical practice, it is important to note
rhage at cannulation sites, and infection.
only patients who were not experiencing cardiopulmo-
ECMO or possibly extracorporeal carbon dioxide nary shock were managed by the protocol. If the mean
removal is considered when patients are refractory to arterial pressure is 60 mm Hg or the patient requires
previously mentioned therapies. ECMO or extracorpo- therapy with vasopressors (other than dopamine at a
real carbon dioxide removal should be performed as dose of 5 mcg/kg/min), fluid management is left to
part of a protocol at experienced medical centers. the judgment of the managing physician. Thus, the
finding that a conservative fluid management strategy
Pharmacotherapy
was associated with better outcomes in this study does
Fluid management not imply that patients who are in shock ought to have
The Acute Respiratory Distress Syndrome Net- fluids restricted. Second, the mean time from ICU ad-
work Fluid and Catheter Treatment Trial (FACTT) mission to protocol implementation was approximately
reported that a conservative fluid management strat- 43 hours.
egy, compared with a fluid liberal strategy, increased A simplified version of the fluid management
the mean number of ventilator-free days in patients protocol (Table 1)was generated by the ARDSnet
with ALI (14.6 vs 12.4 days, respectively; p < 0.001). subsequently which provides useful targets for the
In addition to this beneficial effect on outcomes, the monitoring of intravascular pressure and urine output,
study found that the conservative fluid strategy did not and suggests therapies to help reach those goals
increase the incidence of renal failure or the develop- once the patient has been out of shock for at least 12
ment of shock. Other studies have demonstrated that hours.
albumin and furosemide therapy may be beneficial in
*CVP central venous pressure; PAOP pulmonary artery occlusion pressure; MAP mean arterial pressure.
Patients must have had a MAP of 60 mm Hg without requiring vasopressors for at least 12 h before this
protocol is initiated.
†Furosemide dosing: begin with a 20-mg bolus, 3 mg/h infusion, or last known effective dose. Double each
subsequent dose until the goal is achieved (oliguria reversal or intravascular pressure target), with a maxi-
mal dose of 160-mg bolus or 24 mg/h. Do not exceed 620 mg/d. If the patient has heart failure, treatment
with dobutamine may be considered. Diuretic therapy should be withheld for patients with renal failure,
which is defined as dialysis dependence, oliguria with a serum creatinine level of 2 mg/dL, or oliguria
with a serum creatinine level of 2 mg/dL but with urinary indices indicative of acute renal failure.
‡Fluid bolus: 15 mL/kg crystalloid (round to nearest 250 mL) or 1 unit of packed RBCs or 25 g of albu-
min.

Surfactant replacement the ARDS network investigators in 180 subjects with

persistent ARDS revealed that subjects started on
Surfactant replacement therapy was proposed
steroids after 14 days of diagnosis had an increased
as an adjunctive and anti inflammatory treatment in
mortality rate.
ARDS. Surfactant abnormalities were one of the first
pathophysiologic abnormalities described in patients Buffering agents
with ARDS. A large randomised, controlled clinical trial
Although permissive hypercapnea is a well ac-
testing the efficacy of aerosolized surfactant replace-
cepted practice, severe respiratory acidosis may deter
ment showed no benefit on oxygenation or survival.
physicians from achieving the target of a low-volume,
Inhaled nitric oxide low pressure l u n g protective ventilation strategy.
The urge to increase tidal volumes when plateau air-
Inhaled nitric oxide (NO) induces vasodilatation in
way pressures are above target or when tidal volumes
aerated portions o f the lung, which may cause blood
are already at 6 mL/kg should be resisted, because
flow to redistribute toward ventilated areas, which
it may contribute to additional ventilator associated
results in improved oxygenation. It may also attenu-
lung injury.
ate the activation of polymorphonuclear leukocytes
and platelet aggregation. However, when dissolved Sodium bicarbonate infusions are commonly
in alveolar fluid, NO may react with reactive oxygen used in critical care units to manage life threatening
species to form reactive nitrogen species, which can acidosis, but during the buffering process, CO2 is
be cytotoxic to epithelial cells. released, which raises the partial pressure of CO2.
In patients with impaired ventilation, this phenomenon
Several randomized clinical trials have failed to
may worsen acidosis.
show a survival benefit for inhaled NO when compared
to conventional mechanical ventilation alone. Approxi- For life-threatening respiratory acidosis, tris-
mately 60% of patients demonstrate improvement in hydroxymethly aminomethane may be considered
oxygenation, which may last up to 4 days. if there is no renal dysfunction. Trishydroxymethyl
aminomethane (THAM) is a nonbicarbonate buffer
Inhaled NO should be considered only in pa-
that does not increase CO2 production and in a small
tients with life threatening hypoxemia that failed
observational study improved pH and PaCO2 in patients
previous interventions. Initiate inhaled NO at 1 ppm
with ALI/ARDS and severe acidosis. THAM infusion is
and titrate up every 30 mins until an improvement in
contraindicated in patients with renal insufficiency; its
oxygenation is observed, but not to exceed 10 ppm. If
risks include volume overload, hypoglycemia, and hy-
there i s no immediate r e s p o n s e , then g r a d u a l l y
perkalemia. The dose is based on the base deficit and
discontinue its use. If there is a response, then the
glucose and potassium levels should be monitored.
dose should be decreased daily to the lowest dose
necessary to maintain the target oxygenation and Renal replacement therapies may be considered
should not be used for longer than 4 days. to assist with management of acidosis, particularly if
other indications for renal replacement exist. If life
Glucocorticoids
threatening acidosis persists, then tidal volumes can
Theoretically, glucocorticoids could halt the probe increased by 1 to 2 mL/kg, and the patient s h o u l d
gression to severe and persistent ALI/ARDS by inhibit- be considered promptly for extracorporeal life support
ing neutrophil activation, fibroblast proliferation, and (ECLS).
collagen deposition. Large clinical trials of steroids
Enteral omega-3 fatty acid, γ-linolenic acid, and
in this population h a v e suggested an increased
antioxidant supplementation
incidence of serious neuromyopathic events in steroid-
treated patients but no increased risk for infection as The damage caused by reactive oxygen species
long as strict infection surveillance is implemented. A (ROS) to matrix and cellular proteins, lipids, and nucleic
subgroup analysis from the largest trial performed by acids is a central component of the pathogenesis of ALI/

ARDS. Superoxide (O2 ) and hydrogen peroxide (H2O2) References

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L u n g P ro t e c t i v e S t r a t e g i e s :W h a t W
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lung injury. N Engl J Med 2006; 354:2564 –2575
care with lung protective strategy, more focused clinical
trials on sicker patients with higher predicted mortality
such as a P/F ratio < 200 and shock, are awaited.

Clearing the Cervical Spine in Trauma 145 A S Arunkumar
01 CLEARING THE CERVICAL SPINE IN TRAUMA
Professor, A S Arunkumar
SRMC, Chennai
Introduction The objective of cervical spine clearance is to im-

prove the efficiency and accuracy of the entire trauma
More than 13 million patients with trauma who are
assessment process. This should ideally happen with
at risk for cervical-spine injury present to the emergency
in the emergency room itself, but in certain instances
rooms in the United States and Canada every year.
this may not be possible, for eg; a hemodynamically
(1)
Very few of these patients have a cervical-spine
unstable patient with other major injuries requiring
fracture. However most of these patients get cervical
urgent attention. In such scenarios the process of cervi-
radiography done to rule out a cervical spine injury mak-
cal spinal clearance may be done after the patient has
ing it an expensive low yield inefficient testing method.
become more stable and spinal immobilization must
On the contrary approximately 5-10% of unconscious
continue until the cervical spine is cleared.
patients who present to the ED as the result of a motor
vehicle accident or fall have a major injury to the cervi- Pre requisites for clearance of cervical spine
cal spine. This seemingly divergent scenario, viz need
Two basic principles are applied to clear the cervi-
to obviate unnecessary time consuming investigations
cal spine.
at the same time ensuring that a potentially devastat-
ing spinal injury is not missed makes it imperative 1) A meaningful clinical examination is mandatory
for physicians taking care of these patients to be well before cervical spine clearance .This entails a
versed with decision rules that help in making the right fully lucid patient. (GCS = 15, nothing less!).
diagnosis. 2) Alert, oriented patients should be assessed in
Most cervical spine fractures occur predominantly respect to the presence or absence of symptoms.
at two levels. One third of injuries occur at the level of While doing this the patient should not be intoxi-
C2, and one half of injuries occur at the level of C6 or cated or have any other injury that can distract
C7. Most fatal cervical spine injuries occur in upper the patient from symptoms in the cervical spine.
cervical levels, either at cranio-cervical junction C1 or Based on the above blunt trauma patients can be
C2. Simultaneous cervical spine injuries occur easily divided into three groups -
in patients with head trauma.
A) Alert asymptomatic patients
Definition and objective
B) Alert symptomatic patients
Cervical spine clearance in trauma is defined as
C) Obtunded or unconscious patients
reliably ruling out the presence of cervical injury in a
patient who does not have a spinal injury. It is not in- Clinical decision rules
tended to detect, classify or determine the appropriate
A clinical-decision rule is derived from original
treatment of a cervical spine injury. It is only intended
research and is defined as a decision-making tool that
to declare if an injury is present nor not. This process
incorporates three or more variables from the history,
requires a complete clinical examination and some
examination, or simple tests. Two decision rules have
times additional imaging studies. This should be done
been developed independently to permit more selec-
as early as possible so as to prevent unnecessary im-
tive ordering of cervical-spine radiography and faster
mobilization and consequent problems. However the
clearance of cervical spine thereby enabling better
focus is not on how quickly this is done, but as to how
economy of radiology use and reduced morbidity by
accurately this process is completed.
avoiding unnecessary prolonged immobilization.

a) The National Emergency X-Radiography Utiliza- thought by the clinician to be producing pain suf-
tion Study (NEXUS) Low-Risk Criteria (NLC) in- ficient to distract the patient from a second (neck)
clude five items (Table 1) and were first described injury. Such injuries may include, but are not lim-
in 1992.(2, 3) ited to, any long-bone fracture; a visceral injury
requiring surgical consultation; a large laceration,
Table 1
degloving injury, or crush injury; large burns; or
The NEXUS low risk criteria (NLC) (2) any other injury causing acute functional impair-
Cervical-spine radiography is indicated for ment. Physicians may also classify any injury as
patients with trauma unless they meet all of distracting if it is thought to have the potential
the following criteria to impair the patient’s ability to appreciate other
injuries
i) No posterior midline cervical-spine
tenderness ¶ b) Canadian C-Spine (cervical-spine) Rule (CCR),
ii) No evidence of intoxication § for use with alert patients in stable condition.4
iii) A normal level of alertness †
This rule is based on three high-risk criteria, five
iv) No focal neurologic deficit ƈ
v) No painful distracting injuries. ¥ low-risk criteria, and the ability of patients to rotate
their necks (Fig 1)
¶ Midline posterior bony cervical-spine tenderness

is present if the patient reports pain on palpation
of the posterior midline neck from the nuchal ridge
to the prominence of the first thoracic vertebra, or
if the patient evinces pain with direct palpation of
any cervical spinous process.
§ Patients should be considered intoxicated if they
have either of the following: a recent history pro-
vided by the patient or an observer of intoxication
or intoxicating ingestion, or evidence of intoxica-
tion on physical examination such as an odor of
alcohol, slurred speech, ataxia, dysmetria, or other
cerebellar findings, or any behavior consistent
with intoxication. Patients may also be considered
to be intoxicated if tests of bodily secretions are
positive for alcohol or drugs that affect the level
of alertness.
† An altered level of alertness can include any of
the following: a Glasgow Coma Scale score of 14
or less; disorientation to person, place, time, or
events; an inability to remember three objects at
five minutes; a delayed or inappropriate response
For patients with trauma who are alert (as indicated by a score of 15
to external stimuli; or other findings. on the Glasgow Coma Scale) and in stable condition and in whom
cervical-spine injury is a concern, the determination of risk factors
ƈ A focal neurologic deficit is any focal neurologic guides the use of cervical spine radiography. A dangerous mecha-
nism is considered to be a fall from an elevation ≥3 ft or 5 stairs; an
finding on motor or sensory examination.
axial load to the head (e.g., diving); a motor vehicle collision at high
speed (>100 km/hr) or with rollover or ejection; a collision involving
¥ No precise definition of a painful distracting injury motorized recreational vehicle; or a bicycle collision. A simple rear-
is possible. This category includes any condition

end motor vehicle collision excludes being pushed into oncoming with a partial or complete neurologic deficit is assumed
traffic, being hit by a bus or a large truck, a rollover, and being hit by
a high-speed vehicle
to have a spine injury, and thereby always requires
imaging. Throughout this process, the physician must
Fig.1.Canadian C Spine Rule strictly adhere to all precautionary spine immobilization
For alert patients with trauma who are in stable techniques, even if the initial examination suggests a
condition, the CCR is superior to the NLC with respect complete neurologic deficit.
to sensitivity and specificity for cervical-spine injury (5) C) Obtunded or unconscious patients
(Table 2)
Definitive clearance is not feasible in this group
because of the patient’s inability to undergo a reliable
clinical examination. Adjunctive imaging in this group
can detect obvious cervical injury, but it cannot defini-
tively rule it out, even if it is negative. Strict adherence
to basic principles of cervical spine external support
and/or stabilizing precautions is recommended in this
group of patients. Even if the cervical spine imaging is
Table 2 Sensitivity, Specificity, and Negative Pre- negative, some suggest that cervical spine stabilizing
dictive Value of the Two Rules for 162 Cases of precautions be continued till the patient can be reliably
“Clinically Important” Injury among 7438 Patients examined clinically.
5
Clinical clearance of cervical spine
The above two decision rules can be applied to The prerequisites mentioned earlier must be met
the three groups of patients described earlier to reliably before an attempt at clinical clearance of cervical spine
rule out cervical spine injury. is made.
A) Alert asymptomatic patients History
These patients can be reliably cleared by clini- The history should provide a detailed account of the
cal examination alone without imaging (i.e., no plain following
radiography, computed tomography (CT), magnetic
resonance imaging (MRI), etc.) by using any of the • The events and patient’s condition from immedi-
above decision criteria. Successfully clinically cleared ately postinjury up to the time of presentation to
patients do not require further diagnostic measures, hospital.
and cervical spine precautions can be discontinued. • The mechanism of injury. ( High risk vs low risk
The reliability of cervical spine clearance by physical mechanisms).(High speed vs low speed, direct
examination of the alert patient has been corroborated vs indirect mechanisms)
by a number of studies.6
• Past history with specific focus on cervical spine
B) Alert symptomatic patients pathology.
Alert patients who demonstrate symptoms of neck Special attention must be paid to elderly patients
pain, tenderness, neurologic deficit and decreased even if the injury is seemingly minor as these patients
mobility on physical examination require additional are prone to cervical spinal injury.
diagnostic assessment to effectively clear the cervical
Physical examination
spine. This group also includes patients with a dis-
tracting injury. Additional diagnostic studies typically The physical examination can be accomplished
consist of three-view radiography (anteroposterior, only in patients who demonstrate a GCS of 15. Initial
lateral, open-mouth odontoid) and may also require cervical spine examination consist of a static assess-
adjunctive CT or MRI. An alert patient who presents ment performed with the external cervical support in

place, the neck not manipulated, and the patient in a view alone is typically considered to be insufficient with
supine posture. Look for tenderness, focal spasm or a sensitivity of 74 to 86% among patients with cervical
neurological deficits spine injury.
Once the above maneuvers are successfully The major limitation of plain radiography is its in-
cleared the second phase consists of dynamic evalu- ability to reliably delineate injuries at the occipitocervical
ation done with the external supports removed and cervicothoracic junctions in many patients. The
efficacy of cervical X-rays is highly dependent on the
− Voluntarily neck flexion– extension, rotation, and
quality of the views obtained; however the emergency
lateral bending. Patient should be able to perform
cervical radiographs are frequently inadequate. In one
this without pain or a change in the patient’s neu-
study 94% of the errors leading to missed or delayed
rologic status.
diagnosis of cervical spine injuries were the result of the
− If the patient remains asymptomatic after these failure to obtain adequate cervical spine radiographs.
maneuvers, the patient may be permitted to sit or (7)
stand upright
Lateral view
With a conclusively normal physical examination
A technically acceptable lateral view shows all 7
in both the static and dynamic phases of assessment,
vertebral bodies and the cervicothoracic junction. The
the cervical spine can be clinically cleared without
X-ray must include the base of skull to T1. Anything
adjunctive diagnostic modalities.
less is inadequate. Frequently the inferior cervical spine
If the patient exhibits any pain or change in neu- is not visible due to the shoulders overlying the area.
rological status during the above process then replace Repeat views can be done with downward traction of
the collar to maintain neck stabilization and proceed the arms or the ‘swimmers ‘views. Failing this a CT
with further evaluation. scan should be obtained.
Radiographic evaluation for cervical spine clear- The lateral films should be assessed using 5
ance lines – 4 longitudinal (Fig 2 A,B) and the lines of con-
The following groups of patients need to undergo ra- vergence (Fig 2 C)
diological evaluation
i) Patients who complain about neck pain or tender-
ness
ii) Patients who exhibit neurologic deficits
iii) Patients who do not complain about neck pain
or tenderness but have significant distracting
injuries
iv) Patients with an altered sensorium from head
injury or intoxication
Plain radiography
The accepted standard radiological series cur-
rently consists of a full cervical series (FCS), which
includes anteroposterior, lateral, and open-mouth
odontoid views as the minimum projections neces-
sary for maximum specificity and sensitivity. The first Fig .2A. Normal lateral projection shows the rela-
radiograph to obtain is a single lateral view. The lateral tionships of anterior, posterior, and spinolaminar
lines and prevertebral

Fig. 2 B. Arrows denote soft-tissue line, the dashed Fig 2C. The lines of convergence are drawn down
line is the anterior body line, the stippled line de- the spinous processes and should converge pos-
notes the posterior body line and the dot-dash line teriorly
is the spino-laminar line Anteroposterior view
The first line is that of the soft tissue anterior to This is the least useful view from a clinical stand-
the spinal column. The soft tissue should be less than point.
half the vertebral body width from C1 to C5, and less
than a full body width at C6 and below. A straight line should connect the spinous pro-
cesses bisecting the cervical spine. (Fig 3). If this is
The second line connects the anterior margins not seen, a rotation injury may be present.
of all the vertebrae and is referred to as the anterior
contour line.
The third line should connect the posterior aspect
of all vertebrae in a similar way and is referred to as
the posterior contour line.
The fourth line should connect the bases of the
spinous processes and is referred to as the spinolami-
nar contour line.
Each of these lines should form a smooth lordotic
curve. A bony or ligamentous injury may be present if
disruption is seen in the contour lines.
Further lines are drawn down the spinous process
which should converge posteriorly. Should there be di-
vergence, a posterior column disruption is suspected.
(Fig 2C)
Fig 3. AP X-ray indicating normally aligned
The integrity of the bodies and disc heights should spinous processes
also to be assessed.

Open mouth odontoid view (Fig 4) CT and MRI

This view is used to evaluate an area that is dif- Computer tomography (CT) is useful in delineating
ficult to visualize in the cross-table lateral view. bony structures. CT is indicated should there be poor
The most important structural relationship to visualisation on X-ray such as at the cervico-thoracic
evaluate in this view is alignment of the lateral masses junction or a high index of suspicion of an atlanto-axial
of C1 with respect to the odontoid process. injury. CT can be especially effective in the evaluation
of the upper cervical spine (occiput through C3). In
Masses should be bilaterally symmetric with the
obtunded patients CT has been found to be more sensi-
dens and odontoid process and must be checked for
tive than plain X Rays in detecting spinal injuries.8 CT
fractures or lateral displacement.
is ineffective in detecting some ligamentous injuries.
Assess symmetry of the interspace between C1
MRI is an effective imaging tool for the detection
and C2.
of neural, ligamentous, or disk injury. It is an excellent
modality for assessing the soft tissue. MRI is primarily
indicated for those patients who present with neurologic
deficit for assessment of concomitant spinal cord injury
or assessment of occult ligamentous injury.
Currently the American College of Orthopedics
recommends routine cervical spine CT screening
instead of plain X Rays The American College of
Radiology has stated that CT and MRI are the most
appropriate modalities for cervical spine evaluation in
the obtunded trauma patient
Fig 4 Open mouth Odontoid view showing fracture Important take home messages
of dens
Cervical spine injury should be assumed to be
Dynamic Flexion extension views (Fig 5) present in all patients of trauma until cleared and spinal
immobilization procedures followed.
Should the initial X-rays be normal but there is
clinical concern, dynamic views can be useful. This can Routine rigid neck immobilization is the standard
only be done in the fully alert co operative patient. The recommended for all trauma patients until spine is
patient should perform the motion and not be forced in cleared.
any way. If there is pain while performing the procedure
Cervical spine clearance becomes the focus of
this should be abandoned. These views may unmask
the evaluation, only after “ABCs” of resuscitation have
instability not readily visible on the static views.
been addressed. Cervical spine evaluation can be
safely deferred as long as cervical immobilization is
diligently maintained.
Patients who are awake, alert, sober, and neu-
rologically intact, have no neck pain or midline tender-
ness are extremely unlikely to have an acute C-spine
fracture or instability. Radiography is not indicated in
these patients if they are able to move their neck side
to side without any pain.
Patients, who are awake, alert, neurologically
Fig 5. Normal flexion-extension views demonstrat- intact, cooperative, but do have neck pain or midline
ing good range of motion
tenderness should undergo three-view radiography References

(lateral, AP, open-mouth odontoid) of the C-spine. If
1. McCaig LF, Ly N. National Hospital Ambulatory Medical
C- spine is not adequately visualized on plain X Rays
Care Survey: 2000 emergency department summary.
then axial CT images of suspicious areas need to be
Advance data from vital and health statistics. No. 326.
obtained.
cHyattsville, Md.: National Center for Health Statistics,
Patients who have an altered level of conscious- 2002. (DHHS publication no. (PHS) 2002-1250 02-
ness or cannot describe their symptom should have 0259.)
Lateral, AP, and open-mouth odontoid films with CT
2. Hoffman JR, Schriger DL, Mower W, Luo JS, Zucker M.
supplementation. If all relevant imaging is normal the
Low-risk criteria for cervical spine radiography in blunt
collar can be removed after appropriate evaluation by
trauma: a prospective study. Ann Emerg Med 1992;21:
a doctor skilled in the management of spine-injured
1454-60.
patients.
3. Mahadevan S, Mower WR, Hoffman JR, Peeples N,
When there is doubt leave the collar on.
Goldberg W, Sonner R. Interrater reliability of cervical
Patients who have neurologic deficits (quad- spine injury criteria in patients with blunt trauma. Ann
riplegia or paraplegia) should be evaluated quickly Emerg Med 1998;31:197-201.
and taken off the backboard as soon as possible. A
4. Stiell IG, Wells GA, Vandemheen K, et al. The Canadian
paralyzed patient who is allowed to lie on a hard board
C-Spine Rule for radiography in alert and stable trauma
for more than 2 h is at high risk for developing serious
patients. JAMA 2001;286:1841-8.
pressure sores.
5. Stiell IG, Clement C M, McKnight R D et al. The
Trauma patients who require emergent surgery
Canadian C-Spine Rule versus the NEXUS Low-
before a complete workup of the spine can be accom-
Risk Criteria in Patients with Trauma. N Engl J Med
plished should be transported and moved carefully
2003;349:2510-8.
with the assumption than an unstable spine injury is
present. The collar should be left on and the patient 6. Bachulis BL, Long WB, Hynes GD, Johnson MC Clini-
log-rolled. cal indications for cervical spine radiographs in the trau-
matized patient. Am J Surg (1987) 153(5):473–478
Soft collars permit 75% of normal neck move-
ment. Rigid collars reduce flexion and extension to 7. Davis JW, Phreaner DL, Hoyt DB, Mackersie RC The
about 30% normal and rotation and lateral movement etiology of missed cervical spine injuries. J Trauma
to about 50%. The best immobilization method is to (1993) 34:342–346.
secure patient to a hard board from the head to feet, 8. Schenarts PJ, Diaz J, Kaiser C, Carrillo Y, Eddy V, Mor-
place sandbags at either side of the head and put a ris JA Prospective comparison of admission computed
rigid collar around the neck. This decreases movement tomographic scan and plain films of the upper cervical
to about 5% of normal. spine in trauma patients with altered mental status. J
Trauma (2001) 51:663–668

Intraoperative hypoxemia 152 S Ponnambala Namasivayam
01 INTRAOPERATIVE HYPOXEMIA
Professor of Anesthesiology S Ponnambala Namasivayam

Govt. Stanley Medical College & Hospital
Chennai
1. Introduction • Step wise pattern of reduction in partial

pressure of oxygen from atmospheric air
The term hypoxemia is used to describe ‘defective
through alveolar air, arterial blood, and
oxygenation of arterial blood’. Defective oxygenation,
capillary blood to the cell mitochondrial
even for a brief period of few minutes, may lead onto
level is known as Oxygen cascade. PiO2
irreversible organ damage eg. hypoxic brain death.
149 mmHg; PAO2- 100-105 mmHg; PaO2
Maintaining adequate oxygenation of the patient is
-95-100 mmHg; PcvO2 – 40 mmHg.
one of the prime responsibilities of an anesthesiologist
during the perioperative period. American Society of • When the oxygen supply at the mitochon-
Anesthesiologists (ASA) has included monitoring of drial level goes low, aerobic metabolism
oxygenation as a basic standard of monitoring during stops and anaerobic metabolism takes over
anesthesia. (Pasteur point).
2. Basic concepts of oxygenation • Oxygen is carried in the blood in two forms.
(i) In combination with hemoglobin (ii) In
Certain basic concepts of physiology are dis-
dissolved form in plasma.
cussed here to refresh our knowledge about oxygen-
ation which may be useful to understand intra operative • Oxygen flux is the amount of oxygen that
hypoxemia. leaves the left ventricle per minute.
• Atmospheric air contains 21% of oxygen O2 flux = cardiac output X {(Hb x 1.34 X SaO2/
100) + (0.003X PaO2)}
• Oxygen is manufactured in industries by
fractional distillation of liquid air. • About 1000 ml of oxygen leaves the left
ventricle per minute. This is the amount of
• Oxygen can also be prepared (90-96% O2)
oxygen delivered to the tissues (DO2). Out of
with O2 concentrators, using Zeolite as a mo-
which about 250 ml is utilised by the tissues.
lecular sieve to adsorb nitrogen from air.
750 ml of oxygen returns to the right atrium.
• Oxygen is stored either (i) as a cryogenic Oxygen Extraction Ratio (O2ER) is 0.25.
liquid in containers at low pressures or (ii)
• Arterial O2 content of the blood (CaO2)
as a compressed gas in cylinders at high
pressures. CaO 2= (Hb X 1.34X SaO 2) + (0.003 X
PaO2)
• Oxygen is supplied from the central supplies
to the operation theatres through gas pipe Normal value = 200 ml/ Litre of blood
line distribution system
• Venous O2 Content of the blood (CvO2)
• Terminal units of central pipeline system may
CvO2 = (Hb X 1.34 X SvO2) + (0.003 X
be wall outlets, ceiling mounted hoses, ceil-
PvO2)
ing mounted pendants or ceiling columns.
Normal value = 150 ml/ L of blood
• Anesthesia machine receives oxygen either
(i) from central supply through a hose con- • Oxygen consumption by the body (VO2)
nected to the terminal unit or (ii) from O2 VO2= Q X (CaO2 –CvO2)
cylinders attached to the machine.

Q= Cardiac output (5L) • PaO2, SaO2, CaO2
= 5 X (200 -150) = 250 ml Of the three values used for assessing blood
oxygen levels, absolute value is provided only by the
Normal value= 250ml
CaO2 (units ml O2/dl). This is because CaO2 is the only
• Oxygen extraction ratio (O2ER) value that incorporates the hemoglobin content.
This refers to how much oxygen delivered • PO2: SO2nomogram
to the tissues is taken up.
PaO2 (mmHg) SpO2(%)
O2ER = VO2/ DO2
120 100
= 250ml/1000ml
110 98
= 0.25
92 97
Normal value= 0.2 – 0.3l
80 96
• DO2- VO2 relationship
74 95
Reduction in oxygen delivery will not cause a
69 94
reduction in oxygen consumption. Up to a critical
level (critical dysoxia point), oxygen extraction ratio 66 93
increases from 0.2- 0.3 to 0.5- 0.6 to maintain the VO2.
63 92
After the critical point is reached reduction in DO2 will
cause a reduction in VO2. i.e. oxygen consumption 60 91
becomes supply dependent. 58 90
Normal value= 250ml 56 89
• Partial pressure of oxygen in blood (PO2) 51 86
Oxygen molecules dissolved in plasma (not bound 47 83
to hemoglobin) are free to impinge on the measuring
40 75
oxygen electrode. This “impingement” of free O2 mol-
ecules is reflected as the partial pressure of oxygen. 27 50
Bound oxygen molecules are no longer free to impinge
• Oxygen Dissociation curve is a graphical rep-
on the measuring electrode. Since PaO2 reflects only
resentation showing the relationship between
free oxygen molecules dissolved in plasma and not
oxygen saturation (SO2) and oxygen tension (PO2)
those bound to hemoglobin, PaO2 cannot tell us “how
in the blood.
much” oxygen is in the blood.
• Hypoxia is a condition in which the body as a
• Saturation of oxygen (SaO2)
whole (generalised hypoxia) or a region of the
Binding sites for oxygen are the heme groups, the body (tissue hypoxia) is deprived of adequate
Fe++ porphyrin portions of the hemoglobin molecule. oxygen supply. Here, O2 supply to the tissues
There are four heme sites, and hence four oxygen does not meet with the metabolic demands. The
binding sites, per hemoglobin molecule. Heme sites oc- term hypoxia may be used to describe a situation
cupied by oxygen molecules are said to be “saturated” either inside the body or outside the body (e.g.
with oxygen. The percentage of all the available heme hypoxic gas mixture).
binding sites saturated with oxygen is the hemoglobin
• Hypoxemia is a condition in which there is de-
oxygen saturation (in arterial blood, the SaO2).
fective oxygenation of the blood. Usually it is
described as decreased oxygen tension in the

arterial blood (PaO2< 60mmHg). However, during I) Problems with the O2 delivery system may be
hypoxemia, there is also a reduction in arterial at the level of central O2 supply, pipeline distribution
oxygen saturation (SaO2), arterial oxygen content system, anesthesia machine, ventilator or endotracheal
(CaO2) and central venous oxygen saturation tube.
(ScvO2). Alveolar oxygen tension may or may not
A] Problems at the level of central O2 supplies:
be normal depending on the cause of hypoxemia.
In hypoxemia, Alveolar-arterial oxygen tension (i) Liquid O2 tank may be filled with nitrogen or
difference [P (A-a) O2] is normal. argon
• Although the definitions vary, many a times, the (ii) Incorrect tanks may be placed at the central
terms hypoxia and hypoxemia are used inter- supply manifold
changeably. (iii) Decreasing O2 level at the liquid O2 tank
• Hypoxemia may be categorised as (iv) Gas leak at the manifold
Mild Hypoxemia (arterial saturation is less than (v) Inadequate pressure at the central supply
normal but still < 80%),
(vi) Empty cylinders
Moderate Hypoxemia (PaO2: 60-80%) and
(vii) Depleted cylinders
Severe Hypoxemia (PaO2< 60%)
(viii) Failure to change to secondary supply or
• There are several ways of classifying the causes reserve supply when primary supply fails
of hypoxia. One such classification is (i) hypoxic
hypoxia (ii) anemic hypoxia (iii) stagnant hypoxia (ix) Failure of master alarm system
and (iv) histotoxic hypoxia. B] Problems at the level of pipeline distributing sys-
(i) Hypoxic hypoxia: insufficient O2 reaching the tem:
blood. (i) Leak in the O2 pipelines
(ii) Anemic hypoxia: decreased oxygen carrying (ii) Contamination of Gases
capacity of blood (low Hb or altered Hb )
(iii) Cross connection of pipelines (during con-
(iii) Stagnant hypoxia: decreased blood flow to struction or repair)
the tissues
(iv) Not connecting O2 hose to the terminal unit
(iv) Histotoxic hypoxia: impaired utilisation of
(v) Connecting wrong hose to the terminal unit
oxygen by the tissues.
of O2 pipeline
3. Intra operative hypoxemia : Causes
(vi) Not connecting the O2 hose to the anesthesia
The causes of intra operative hypoxemia are machine
many. Often one or more of these causes may coexist
(vii) Connecting wrong hose to the O2 yoke
and there may be considerable overlapping of mecha-
nisms which ultimately result in arterial hypoxemia. A (viii) Inadvertent switching of Schrader adapter
systematic approach is essential for identifying the on piped lines
cause and to treat it. (ix) Terminal units labelled wrongly
For practical purposes the causes of hypoxemia may (x) Wrong outlet connectors installed
be classified into two.
C] Problems at the level of O2 cylinders attached to
I) Problems with the O2 delivery system the anesthesia machine:
II) Problems with the patient. (i) Empty cylinders

(ii) Depleted cylinders (vi) Cuff herniation

(iii) Substitution of non-oxygen cylinder at the (vii) Cuff rupture
O2 yoke (viii) Tube obstructing opening of right upper lobe
(iv) Erroneously filled O2 cylinder bronchus
(v) Insufficiently opened cylinder II) Hypoxemia due to problems with the patient
D] Problems at the level of the anesthesia ma- Intra operative hypoxemia may occur because of
chine: the usual changes that occur during anesthesia or due
to intra operative complications.
(i) Incorrect setting of flow meter
A] Hypoventilation:
(ii) Use of fine O2 flow meter instead of course
flow meter A spontaneously breathing anesthetised patient
may hypo ventilate due to drug induced respiratory
(iii) Crack in the O2 flow meter tubes depression (sedatives, narcotics). In a patient who is
(iv) Transposition of rota meter tubes paralysed and ventilated, hypoventilation may occur
due to inadequate IPPV.
(v) Leak in the machine
B] Reduced functional residual capacity:
E] Problems at the level of the anesthesia ventilator:
Induction of anesthesia causes a reduction in
(i) Incorrect ventilator setting FRC by 15- 20%. Maximum reduction in FRC occurs
(ii) Low tidal volume within the first few minutes of induction. Reduction in
FRC is seen equally in both spontaneous breathing and
(iii) Low respiratory rate controlled ventilation. The decrease in FRC continues
(iv) Inadequate minute volume in the post operative period also. The reduction in FRC
is more in obese patients. Application of PEEP may
(v) Power failure
compensate the decrease in FRC.
(vi) Driving gas failure C] Increased airway resistance:
(vii) Disconnection of tubing During anesthesia, increase in airway resistance
(viii) Wrong connection of tubing may occur due to i) reduction in FRC ii) decrease in
calibre of airways iii) endotracheal intubation (ETT
(ix) Failure to switch on the ventilator
decreases the size of the trachea by 30- 50%) iv)
(x) Failure to résumé ventilation after a period anesthesia apparatus iv) pharyngeal obstruction (e.g.
of purposeful apnoea snoring) in an unintubated patient. v) laryngospasm vi)
obstruction of ETT by secretions, kinking, cuff hernia-
F] Problems at the level of the anesthesia circuit:
tion vii) bronchospasm.
(i) Disconnection (most common cause)
D] Atelectasis:
(ii) Leak
Atelectasis is a condition of alveolar collapse. It
G] Problems at the level of endotracheal tube: may be micro atelectasis, macro atelectasis or lobar
collapse depending on the degree of alveolar collapse.
(i) Esophageal intubation
This leads to V/Q mismatch, R-L shunting and arterial
(ii) Endobroncheal intubation hypoxemia. Atelectasis may occur due to airway se-
cretions, compression by packs, wedge and prolonged
(iii) Accidental extubation
surgical procedures in unusual positions. Auscultation
(iv) Tube kinking may reveal crepitations with diminished air entry. PEEP
(v) Tube obstruction may be useful in such situation.

E] Absorption atelectasis: I] Poor oxygen delivery to the tissues:

Alveolar collapse can occur when the patient is Systemic hypo perfusion (hypovolemia)
getting high FiO2. When PAO2 rises, the rate at which O2
Embolus
moves from the alveoli to the capillary blood increases.
When the absorption rate is more than the inspired flow Sepsis – acute lung injury
of gases, the lung unit collapses. Absorption atelectasis
Local problems (cold limb, Reynaud phenomenon,
occurs when FiO2 is high; V/Q is low; time of exposure
sickle cell disease)
of lung unit low V/Q ratio to high FiO2 is long and CvO2
is low. J] Increased oxygen demand:
F] Diffusion Defect: Malignant hyper pyrexia

Even though adequate oxygen is supplied to the Shivering
alveoli, there may be a defect at the alveolar level which
Sepsis.
prevents its absorption into blood. This may occur with
thickened alveolar membrane, thickening of air-blood 4. Intra operative hypoxemia during specific
interface (alveolar-capillary block), inflammation, situations
edema, fibrosis or loss of alveolar surface area. E.g.
Hypoxemia can occur any time during anesthesia,
sarcoidosis and emphysema.
induction, maintenance or reversal. It can occur preop-
G] Shunt: eratively, intra or postoperatively. It can occur during
(i) Inadequate ventilation: intubation or extubation. Hypoxemia may develop dur-
ing general anesthesia or regional anesthesia. It may
Absorption atelectasis occur in unintubated as well as intubated patients. It
Airway secretions-blockage of alveoli may develop in spontaneously breathing patients or
controlled ventilation patients. It can occur in children,
Pulmonary aspiration
young adults or elderly patients. It may occur due to
Pulmonary edema pre-existing conditions or due to intra operative compli-
Inhibition of HPV-vasodilators (SNP, NTG) cation. Hypoxemia can occur during any type of surgical
procedures. Certain specific situations are given below
(ii) Inadequate perfusion:
although the list is not complete.
ASD/ VSD
Hypoxemia during Laparoscopic surgery is very
Patent foramen ovale common. The mechanism of hypoxemia during lap-
Pulmonary embolism aroscopic surgery may be
H] Inhibition of hypoxic pulmonary vasoconstriction (i) Pre-existing conditions:

(HPV): Cardio-pulmonary dysfunction
When PAO2 decreases in a region of lung pulmo- Morbid obesity
nary vasoconstriction occurs at that particular region.
This hypoxic pulmonary vasoconstriction is a protective (ii) Hypoventilation:
phenomenon. HPV diverts blood flow from the hypoxic Patient position
regions of the lung to better ventilated normoxic regions
thus decreasing V/Q mismatch maintaining PaO2. Pneumoperitoneum
Inhibition of HPV may lead on to arterial hypoxemia. Tracheal tube obstruction
Factors which inhibit HPV are inhaled anesthetics,
Inadequate ventilation
vasodilators (SNP, NTG), hypocapnia, hypothermia
and thromboembolism.

(iii) Intrapulmonary shunting: by the presence of air in the pleural cavity and lung
collapse. X-ray chest may not be always possible in
Decreased FRC
the intra operative setup. Prompt diagnosis is essential
Endobronchial intubation because tension pneumothorax collapses the lung; gas
Pneumothorax exchange is compromised; severe arterial hypoxemia
occurs. Immediate intervention should be done by in-
Emphysema (subcutaneous/mediastinal) serting an i.v. cannula in the second intercostal space
Pulmonary aspiration of gastric contents at the midclavicular line. Definite treatment is with an
intercostal drainage.
(iv) Reduced cardiac output:
Pulmonary edema
Haemorrhage (trocar injury)
Pulmonary edema may result from i) increase in
IVC compression preload (Fluid overload). ii) Decrease in myocardial
Impaired venous return contractility (CCF) iii) Increase in capillary perme-
ability (sepsis, ARDS, neurogenic pulmonary edema,
Arrhythmia (hypercarbia or inhaled anesthet-
high altitude pulmonary edema) iv) Negative pressure
ics)
pulmonary edema (relief of upper airway obstruction).
Myocardial depression (drug induced/acido- During early stages, fluid accumulation occurs in the
sis) interstitial space. Airway pressure increases. Lung
compliance decreases. In the later stages, fluid floods
Reduced cardiac output
into the alveoli. Management is aimed at identifying the
CO2 embolism cause and treating it. Steps are taken to decrease the
When hypoxemia occurs during laparoscopic preload, improve the myocardial contractility, restore
surgery, make the operating table and patient straight; normal sinus rhythm, treat sepsis, increase FiO2 and
give 100% O2. Release pneumo-peritoneum. Switch apply PEEP.
off the volatile anesthetics. Check the tube position; Hypoxemia in Children
find out the cause of hypoxemia. In cases of refractory
Neonates and infants are prone for more rapid
hypoxemia or high air way pressure, convert to open
desaturation during Anesthesia.
procedure. In patients with pulmonary dysfunction,
pre-op ABG may be done and intra-operative radial 1. Small diameter of airways increases the airway
catheterisation may be considered. resistance. (Resistance is inversely proportional
to the radius raised to the forth power.
Pneumothorax
2. Chest wall and airway are highly complaint. Nega-
Pneumothorax may develop in polytrauma tive intra thoracic pressures partly maintained.
patients, chest trauma patients, in emphysematous Each breath is accompanied by functional airway
patients during IPPV, after central venous cannula- closure.
tion (IJV/SCV), after supraclavicular brachial plexus
3. Oxygen consumption is 2-3 times as high as in
block. Spontaneously breathing patient may present
adults.
with dyspnea, tachycardia, tachypnea and hypoten-
sion. In a patient who is on controlled ventilation, lung 4. In premature infants work of breathing is 3 times
compliance decreases; reservoir bag becomes tight; that of the adult.
peak airway pressure increases. Chest expansion is 5. Children acquire type 1 muscle fibres in respira-
decreased. There is diminished air entry on ausculta- tory muscles only at the age of 2. Only type 1
tion and hyper resonance on percussion. The condition muscle fibres are capable of repeated exercise.
may be confused with bronchospasm or hyperinflation Hence neonates & premature infants go in for
in COPD patients. Chest X-ray confirms the diagnosis early fatigue & apnoea.

6. Premature infants have deficient surfactant. They preoxygenation is less effective in obese patients.
are prone for Respiratory Distress Syndrome. *Time for desaturation after safe apnoea (Apnoeic
oxygenation reserve) is reduced. *FRC is further re-
7. Because of the difference in the airway anatomy,
duced in supine position and still further decreased
there may be intubation difficulty. Mask ventilation
with induction of anesthesia.*Airway resistance is
is also difficult. Endo bronchial intubation and ac-
increased. *Obese patients are prone for pulmonary
cidental extubation are possible.
aspiration of gastric contents. *They are more sensitive
Hypoxemia in Parturients to depressant effects of hypnotics and opioids. *Par-
Pregnant women have a reduced FRC by 20%. enteral or neuraxial opioids carry potential fatal/near
Oxygen reserve is decreased. Oxygen consumption fatal respiratory misadventure. There may be associ-
is increased by 20 %. Parturients are more prone for ated cardiovascular abnormalities, COPD, pulmonary
precipitous fall in PaO2 even after a brief period of ap- hypertension,RVH, RVF, corpulmunale etc.
noea. (Failed endotracheal intubation is more common Following factors should be considered
in obstetric patients than in surgical patients). Difficulty
Preoperative polysomnography. (Definitive diag-
in intubation, delayed intubation and pulmonary aspi-
nosis for obstructive sleep apnoea syndrome is poly-
ration of gastric contents may worsen the situation.
somnography), supine room air SpO2, room air ABG,
regional anesthesia is preferable.Preoxygenation is a
pulmonary function test,preop respiratory preparation
must before induction of GA. Rapid sequence intuba-
(cessation of smoking, antibiotics,bronchodilators,
tion with Sellick’s maneuver is to be done. In case of
breathing exercises); antacid premedication; avoid-
failed intubation, algorithm for failed intubation should
ance of sedative premedication; awake intubation;
be followed and alternate plan for oxygenation should
induction and recovery inupright position; post op
be readily available. Oxygenation should be monitored
semi-recumbent position; intense post op monitoring
continuously.
and nursing care; oxygen therapy alone may not be
Hypoxemia in elderly patients sufficient. Prophylactic CPAP/ BiPAP may be neces-
Elderly patients coming for anesthesia are more sary; early mobility.
prone for hemoglobin desaturation Hypoxemia during one lung ventilation
1. Compromised respiratory system: loss of lung Hypoxemia occurs in almost all cases during
elastin, reduced thoracic compliance, reduced one lung ventilation. The reason for hypoxemia is
alveolar surface area, increased residual volume, ventilation-perfusion mismatch, because the non
loss of vital capacity, impaired efficiency of gas –dependent lung is not ventilated but continues to get
exchange, increased work of breathing perfused. Following are the measures taken to main-
2. Compromised cardio-vascular system tain oxygenation during OLV.i) Two lung ventilation as
long as possible. ii) High FiO2= 1.0 iii) Begin OLV with
3. There is decreased requirement of I.V.induction
Vt=10mi/kg iv) Adjust RR so that PaCO2=40mmhg v)
agents, opioids, benzodiazepines and inhalational
Monitor oxygenation and ventilation continuously. If
agents
severe hypoxemia persists, vi) Non-dependent lung
4. Prolonged drug effect is seen after sedatives, CPAP vii) Dependent lung PEEP vii) Intermittent two
narcotics, and muscle relaxants. lung ventilation viii) Clamp pulmonary artery as soon
as possible. Other causes of hypoxemia should not
Hypoxemia in obese patients / bariatric surgery
be forgotten (e.g.) Depleted O2 supply, malposition
Hypoxemia in obese patients is due to* Difficult or obstruction of DLT, decreased cardiac output or
mask ventilation * difficult laryngoscopy *difficult intu- conditions which increase O2 consumption (shivering,
bation *Decreased lung volumes and capacities FRC, Hyperthermia)
ERV, VC. ERV is the only oxygen reserve. Hence

Hypoxemia during orthopaedic procedures to post-dialysis hypoxemia which is similar in patients

with or without lung disease. iii) Reduction in intra
Hypoxemia is not uncommon during or after or-
vascular volume and cardiac output can also cause
thopaedic surgical procedures.
hypoxemia. However, the main reason for hypoxemia
The possible causes may be, is hypoventilation. PAO2 decreases; P (A-a) O2 does
1. Difficulty in intubation in cases of ankylosing not change; PACO2increases. This should be born in
spondylitis, rheumatoid arthritis, fracture cervical mind when a patient on dialysis comes for anesthesia
spine, prior cervical spine fusion and congenital especially for short surgical procedures under LA with
deformities of cervical spine. spontaneous breathing. Treatment is with oxygen.
2. Unusual positions during surgery: (eg. Hypoxemia in liver disease

prone,sitting, lateral decubitus, fracture table). Hypoxemia is common in chronic liver disease
ETT migration,kinking,dislodgement. patients e.g. cirrhosis of liver. Reasons: i) Ascites and
3. Lateral position for prolonged periods may pro- pleural effusion may interfere with gas exchange by
duce dependent lung hypoventilation. restricting ventilation. ii) Many of these patients smoke;
COPD may produce V/Q mismatch and abnormal gas
4. Upper airway edema in long procedures may
exchange. iii) Repeated episodes of pneumonia. iv)
result in post-operative respiratory dysfunction.
CLD patients have a decreased HPV response. Hence,
5. Associated rib injury in polytrauma patients. there is increased blood flow to poorly ventilated lung
units. iv) High cardiac output is seen in CLD patients.
6. Pulmonary embolism. (Fat, thrombus, bone ce-
The transit time in pulmonary capillaries is less and thus
ment, bone marrow, air)
the O2 uptake is low. Poor DLCO is seen in cirrhotic
– Up to 75% of fracture femur patients may patients.
develop DVT
Hypoxemia at high altitude
– 10-15% of patients with long bone fracture
Anesthesiologists who work at high altitudes
develop fat embolism
above the sea level should be aware of decrease in
– Hypoxemia due to bone cement embolism PaO2. This is because of the low barometric pressure
may persist for 5 days post operatively. and proportionately lower PiO2. One should be aware
7. Pneumothorax may develop after supraclavicu- of this when resuscitating and transporting a patient in
lar brachial plexus block for upper limb surgical aircraft.
procedures. Diffusion hypoxia (Fink’s effect)
8. Major blood loss or fluid overload. Diffusion hypoxia occurs at the end of general
9. Hypoventilation due to sedatives during regional anesthesia when N2O: O2 is switched off and when
anesthesia. the patient is allowed to breathe air. Nitrous oxide is
31 times more soluble than nitrogen. For every one
10. Transient fall in CVO2 is seen after tourniquet molecule of nitrogen entering into blood from alveoli,
release. 31 molecules of nitrous oxide enters into alveoli from
Hypoxemia in renal disease blood. The alveolar oxygen is diluted and hypoxemia
results. This is more common during the first 5-10
Arterial hypoxemia may be observed during or
minutes of recovery. Administration of 100% O2 is es-
after dialysis. It is seen with both acetate and bicarbon-
sential to overcome the situation.
ate dialysates. Mechanism: i) Hypoventilation: Acetate
removes the carbon dioxide load and bicarbonate dialy- 5. Hypoxemia - diagnosis
sis suppresses the respiratory drive due to an increase During early days of anesthesia, defective oxy-
in bicarbonate. ii) V/ Q mismatch may also contribute genation of the patient was identified by cyanosis and
dark blood in the surgical field. Cyanosis occurs when • Expose the chest, breathing circuit and all
the deoxygenated hemoglobin is > 5g/100 ml. Ap- airway connections.
preciation of bluish discolouration of skin and mucus
• Give 100% O2 (FiO2=1.0)
membrane is a subjective phenomenon. Cyanosis is
usually observed when the Hb saturation is <85%. This • Hand ventilate (Switch off anesthesia ventila-
corresponds to a PaO2 of 45-50 mm Hg in adults and tor); Give few large breaths; Get the feel of
35- 40 mm Hg in infants. Cyanosis may be observed the bag.
when there is no hypoxemia e.g. methemoglobinemia
• Confirm FiO2. If the FiO2 is not at the set
/ sulphemoglobinemia. Cyanosis may not be apparent
level,
in the presence of anemia or peripheral vasoconstric-
tion. Look at cylinder colour code.
Appreciation of dark blood is again a subjective Whether the cylinder has O2 or is it de-
phenomenon. Sometimes it may be too late to appre- pleted.
ciate dark blood. By the time dark blood is observed,
Confirm that the pipe line connections are
irreversible damage would have already occurred.
all right.
Several monitors are used now to detect hypox-
If in doubt about the gas in the cylinder or
emia. Pulse oximeter is the most commonly used one.
if there is doubt about cross connection of
Other monitors include, oxygen analyser (FiO2 monitor),
ABG, ScvO2, Other monitors which may be useful in pipelines - Use a separate cylinder supply
identifying the cause of hypoxemia are capnography, Consider replacing the anesthesia machine
airway pressure monitorand ECG. with another one
ASA monitoring standards As a last resort, think of disconnecting the
Standard I states that a qualified anesthesia pro- machine and ventilate with an AMBU bag.
vider will be present with the patient throughout the • Confirm the ETT position.
anesthetic.
Auscultate and confirm bilateral equal air
Standard II states that the patient’s oxygenation, entry
ventilation, circulation, and temperature will be continu-
ally monitored. Rule out endobronchial intubation
Assessment of oxygenation involves two parts: Rule out ETT kinking, obstruction (secre-
tions, mucus, blood or foreign body). Insert
(i) Measurement of inspired gas with an oxygen
a suction catheter or bougie or FOB. Re-
analyzer and
move the secretions. Consider changing the
(ii) Assessment of hemoglobin saturation with ETT.
a pulse oximeter and observation of skin
• Check whether the ventilator pattern is cor-
colour.
rect.
O2 analyser placement: The sensor should be placed
on the inspiratory side of the system. The sensor should Hand ventilate rather than using a ventila-
be upright or tilted slightly to prevent moisture from ac- tor.
cumulating on the membrane. The junction between the Use a Bain’s circuit instead of circle sys-
cable and the sensor should not be under strain. tem.
6. Hypoxemia management Try a self-inflating bag (AMBU bag).
Management of hypoxemia is aimed at identifying Consider using a mask instead of ETT.
the cause and treating it. General measures include
the following. • Find out the exact site of leak or block.

• Decreased FRC: Hypoxic guard

Hyper inflate gently with PEEP. O2 proportionating devices (O2 ratio monitor
controller/ Link 25 system),
• Absorption atelectasis:
O2 flow meter tubes placed downstream
Decrease FiO2
Check valve to prevent flow of gases from
Remove secretions.
the machine to the cylinder or pipeline.
• Increased airway resistance (bronchos-
Minimum mandatory O2 flow
pasm):
• Cylinder should always be kept closed when
Deepen anesthesia
pipeline is use. Cylinder should be used as
Add volatile anesthetics (halothane/ sevo- a reserve in case if pipeline supply fails.
flurane)
• Pressure gauge (cylinder or pipeline) should
Stop the precipitating drug (Histamine re- be observed repeatedly during use.
leasing drug like atracurium)
• Always use FiO2 monitor
Salbutamol nebulisation
• Careful check-up should be carried out after
Inj. Aminophylline 5mg/kg bolus followed by installation, alteration, repair of pipelines and
0.5-1mg/kg/hr infusion. after construction & civil work.
• R-L shunt: • Master alarm system should be installed and
Cardio vascular support maintained to warn about depletion of central
O2 supply.
Increase SVR: Lifting the legs, vasopressors
(noradrenaline), IVF. • Ensure correct placement of ETT.
Decrease PVR: Remove PEEP, avoid high • ASA monitoring standards should be fol-
intra thoracic pressure, maximise FiO2 , nitric lowed.
oxide. • Adequate pre-operative investigations and
• Hypovolemia: IVF, Blood assessment.
• Increased O2 demand: Give 100% O2. • Proper pre-operative preparation of patient
• Pneumothorax: ICD • Optimisation of co-morbid conditions.
• Methemoglobinemia: 100% O2, Inj. Methyl- • Continuous vigilance is the price of safety.
ene blue1-2 mg i.v. • High degree of suspicion is to be main-
7. Hypoxemia – prevention tained.
• Before every anesthetic, anesthesia machine 8. Conclusion

check-up should be properly carried out. Intra operative hypoxemia is an emergency situ-
This should include check-up for emergency ation which requires immediate intervention. It is a life
ventilation system, high pressure system, threatening situation if the hypoxemia is severe, rapid
low pressure system, scavenging system, and sustained. Hypoxemia is better prevented than
breathing system, manual and automatic treated. When hypoxemia occurs, it should be promptly
ventilating system and monitoring system. diagnosed and properly managed.
• Use anesthesia machine with
O2 pressure failure alarm

Recent Advances in Labour Analgesia 162 Sunil T Pandya
01 RECENT ADVANCES IN LABOUR ANALGESIA
Head of Anesthesia, Pain and Critical Care, Sunil T Pandya

Prerna Anesthesia and Critical Care Services,
Fernandez Hospital, Hyderabad
The following write up has been obtained “ With the clinicians to minimize the failure rates and many
the permission of Editorial Board , IJA” have updated novel drug delivery modalities like PCEA and computer
few advances since then! integrated PCEA has contributed to over all maternal
satisfaction and safety.
Abstract
Introduction
The advances in the field of labour analgesia
has tread a long journey from the days of ether and “The delivery of the infant into the arms of a con-
chloroform in 1847 to the present day practice of com- scious and pain-free mother is one of the most exciting
prehensive programme of labour pain management and rewarding moments in medicine” Moir Pain relief
using evidence based medicine. in labour has always been surrounded with myths and
controversies, hence providing effective and safe anal-
Newer advances include introduction of newer
gesia during labor has remained an ongoing challenge.
techniques like combined spinal epidurals, low dose
Historically, the era of obstetric anesthesia began with
epidurals facilitating ambulation, pharmacological
James Young Simpson, when he administered ether
advances like introduction of remifentanil for patient
to a woman with a deformed pelvis during childbirth.
controlled intravenous analgesia, introduction of
His concept of ètherization of labour’ was strongly
newer local anesthetics and adjuvants like ropivacaine,
condemned by critics! The religious debate over the
levobupivacaine, sufentanil, clonidine, neostigmine,
appropriateness of anesthesia for labour (1) continued
use of inhalational agents like sevoflourane for pa-
till 1853, when John Snow administered chloroform to
tient controlled inhalational analgesia using special
Britain’s Queen Victoria during the birth of her eighth
vaporizers, all have revolutionized the practice of pain
child, Prince Leopold (2).
management in a laboring parturients. Technological
advances like usage of ultrasound to localize epidu- JY Simpson also proposed that, “Medical men
ral space in difficult cases minimizes failed epidurals may oppose for a time the super-induction of anes-
and introduction of novel drug delivery modalities like thesia in parturition, but they will oppose it in vain; for
patient controlled epidural analgesia pumps, com- certainly our patients themselves will force use of it
puter integrated drug delivery pumps have improved upon the profession. The whole question is, even now,
overall maternal satisfaction rate and have enabled one merely of time.” This time came in 1950’s when
us to customize a suitable analgesic regimen for each neuraxial techniques were introduced for pain relief in
parturient. labour and during the last two decades (13), there have
been several advances that lead to comprehensive
Recent randomized controlled trials and Cochrane
and evidence based management of labour pain.
studies have concluded that association of epidurals
with increased cesarean section and long term back Modern neuraxial labour analgesia reflects a shift
ache remains only a myth. Studies have also shown in obstetrical anesthesia thinking away from a simple
that the newer low dose regimes does not have sta- focus on pain relief towards a focus on the overall
tistically significant impact on the duration of labour, quality of analgesia (14). The International Association
breast feeding and also reduce instrumental delivery for the Study of Pain (IASP) declared 2007-2008 as the
rates thus improving maternal and fetal safety. ‘‘Global Year against Pain in Women – Real Women,
Real Pain’’. The focus was to study both the acute pain
Advances in medical technology like usage of
and chronic pain in women. Labour pain was found to
ultrasound for localizing epidural space have helped

a good study model for treating acute pain. Increasing cians as a sole anesthetic for labour pains is not safe,
knowledge of the physiology and pharmacotherapy of as the laboring often require anesthetic dosages that
pain, and the development of obstetric anesthesia as may compromise the airway. Further the benzodiaz-
a subspecialty has improved the training in obstetric epines used to counteract delirium can cause neonatal
anesthesia leading to overall improvement in the quality respiratory depression. Its usage in labour should be
of labour pain relief. discouraged.
In many countries today, the availability of regional Fentanyl is a highly lipid soluble synthetic opioid
analgesia for labour is considered a reflection of stan- with analgesic potency 100 times that of morphine and
dard obstetric care. According to the 2001 survey, the 800 times that of pethidine (5). Its rapid onset of action
epidural acceptance is up to 60% in the major mater- within 2-3 minutes after intravenous route with short
nity centers of US. National Health Service Maternity duration of action and with no major metabolites makes
Statistics of 2005–2006 in U.K reported that one third it superior for labour analgesia. It can be administered
of the parturients chose epidural analgesia.. In our in boluses of 25-50 micrograms every hourly or as a
country, the awareness is still lacking and except few continuous infusion of 0.25 micrograms per Kg per
centers, which run a comprehensive labour analgesia hour. Because of is pharmacokinetics and pharma-
programme, the national awareness or acceptance of codynamics, it is suitable to be administered by PCA
pain relieving options for women in labour virtually does (Patient controlled intravenous analgesia).
not exist.
Tramadol is a pethidine like synthetic opioid
Methods of pain relief in labour having low affinity for mu receptors. Its potency is
Non pharmacological methods 10% that of morphine. It has no clinically significant
respiratory depression at usual doses of 1-2 mg per
Transcutaneous electrical nerve stimulation
Kg body weight. Onset of action is within 10 minutes
(TENS), continuous support in labour, touch and mas-
after intramuscular administration and the duration
sage, water bath, intradermal sterile water injections,
lasts approximately for 2-3 hours. Claahsen-van der
acupuncture and hypnosis, all may be beneficial for
Grinten (6) demonstrated high placental permeability
the management of pain during labour (3). However,
for tramadol, however, neonates possess complete
the number of women studied has been small and
hepatic capacity to metabolize tramadol. Compared
there have been no proven scientific data analysis of
with pethidine mothers receiving tramadol had higher
the quality of pain relief offered by these techniques.
pain scores, thus cross over to alternate methods of
There is some evidence suggesting that water immer-
relief is very common.
sion during the first stage of labour reduces the use of
epidural analgesia. A lack of data for some compari- Butorphanol is an opioid with agonist-antagonist
sons prevented robust conclusions. properties that resemble those of pentazocine. It of-
fers analgesia with sedation. It is five times as potent
Parenteral narcotics
as morphine and 40 times as potent as pethidine. The
Systemic opioids have been used since 1840s dose of butorphanol is 2 mg to 4 mg intramuscularly.
and are the most widely used medications for labour Butorphanol 2 mg produces respiratory depression
analgesia. similar to that with morphine 10 mg or pethidine 70 mg;
Pethidine (meperidine), an opioid agonist, is the however, there is a ceiling for respiratory depression
most frequently used opioid world wide. Its effect on at higher doses with butorphanol (7). It is not frequently
progress is contentious. Sosa et al (4) have concluded used for labour analgesia as it produces more seda-
that pethidine should not be administered in parturients tion.
with cervical dystocia, as there is no benefit and a Remifentanil
greater risk of neonatal adverse outcome.
Remifentanil is an ultra-short acting synthetic
Intravenous ketamine, promoted by some clini-
potent opioid. It has a rapid onset of action and is

readily metabolized by plasma and tissue esterases dependent mother (9).

to an inactive metabolite. The effective analgesia half-
For reversing maternal respiratory depression,
life is 6 minutes, thus allowing effective analgesia for
the dose is 0.4 mg intravenously. It should be noted
consecutive uterine contractions. It readily crosses
that it also reverses the analgesic action. The half life
placenta, but is extensively metabolized by the fetus.
of naloxone is shorter and may require repeat admin-
Because of its pharmacokinetic profile, this agent has
istration if the duration of action of narcotic is longer.
advantage over other opioids for labour PCA.
Inhalational methods
The recommended dose of remifentanil is intra-
venous bolus of 20 micrograms with a lock out interval Only agent that has survived the test of time is
of 3 minutes on the PCA pump. In a study by Novelli nitrous oxide (Entonox), which is administered as 50:50
et al (8), on the efficacy and safety of intravenous infu- mixtures of oxygen and nitrous oxide. Other agents
sion of remifentanil in 205 parturients, remifentanil that have been tried in recent years are sevoflurane
was administered as a continuous infusion. The initial (Sevox), isoflurane and enflurane, the volatile anes-
infusion of 0.025 micrograms per kg per minute was thetic agents.
increased in a stepwise manner to a maximum dose Entonox
of 0.15 microgram per Kg per minute. Maternal pain,
A systemic review of the use of entonox in labour (10)
other maternal and fetal variables, side effects, and
concluded that entonox is certainly not a potent anal-
satisfaction were recorded. The mean (±sd) visual
gesic; studies suggest beneficial effects on parturients
analog score before the start of the infusion was 9.4 ±
if the method of inhalation is properly followed. Places
1.2 cm and decreased to 5.1 ± 0.4 cm after 5 min and
where neuraxial techniques are not practiced, and in
3.6 ± 1.5 cm after 30 min.
parturient with short labour, entonox inhalation is a
Most studies concluded that maternal monitoring useful method. Obstetric Anesthesia Association, UK
during intravenous PCA with remifentanil should be one (2005) guidelines states that entonox is being phased
to one as maternal hypoventilation is more common out from UK in view if poor analgesic efficacy and en-
and there are more episodes of oxygen saturation fall- vironmental pollution.
ing to < 94% on pulse oximetry. However it is a prom-
Sevox – Patient controlled inhalation analgesia
ising solution in women requesting labour analgesia,
(PCIA)
when neuraxial techniques are contraindicated.
Sevoflurane is a volatile inhalational agent com-
Opioid antagonists
monly used during general anesthesia. Because of its
Naloxone is the opioid antagonist of choice for short onset and offset of action, it appears to be the
reversing the neonatal effects of maternal opioid ad- best suited inhalational agent for labour analgesia and
ministration. It should be noted that there is no benefit can be administered as patient controlled inhalation
to maternal administration of naloxone during labour anesthesia (PCIA) (11). It is used in the concentration of
or just before delivery. It is best to administer directly 0.8% with oxygen and needs specialized equipment.
to new born if there is any neonatal respiratory depres- Further, there is a concern for environmental pollution
sion. The dose of naloxone for reversing neonatal and maternal amnesia and loss of protective airway
respiratory depression is 0.1 ml per Kg. Administra- reflexes. Larger studies are needed to assess the
tion of naloxone is not recommended during primary incidence of maternal compromise.
steps of neonatal resuscitation. The preferred route of
Regional analgesia in labour
administration is intravenous. Intramuscular route is ac-
ceptable if intravenous access is not available, although Central neuraxial analgesia is the most versatile
the absorption is delayed. Endotracheal administra- method of labour analgesia and the gold standard tech-
tion of naloxone is not recommended. Naloxone may nique for pain control in obstetrics currently available(12).
precipitate a withdrawal in the newborn of the opioid Use of neuraxial techniques has increased dramatically

in the last 20 years especially in the west and few dedi- ment of techniques (sequential CSEA) and availability
cated centers in India. It is unlikely that this will change of newer drugs and adjuvants. The technological ad-
soon, as compared to other techniques; satisfaction of vances have facilitated the various modalities of novel
birth experience is greater with neuraxial techniques. drug delivery systems like patient controlled infusion
regimes and newer randomized controlled trials have
There have been several exciting advances in
helped to solve several controversies associated with
the field of neuraxial analgesia (15, 16) in terms of refine-
neuraxial analgesia. They advances are tabulated as
Table 1: Recent advances in neuraxial analgesia
1. Technical advances
a. Combined spinal epidural analgesia
b. Continuous spinal analgesia using micro catheters
c. Ambulatory epidurals, concept of MLAV and MLAD*, Low dose and ultra low dose
epidurals
2. Pharmacological advances
a. Ropivacaine, levobupivacaine
b. Newer opioids: sufentanil, remifentanyl
c. Adjuvants : clonidine & neostigmine
3. Technological advances
a. Availability of Ultrasound to facilitate localization of epidural space, minimizing failures
b. Patient controlled epidural analgesia regimes
4. Newer insights into myths & controversies associated with neuraxial techniques
a. Effect and timing of epidural on cesarean section, maternal and neonatal outcome, breast
feeding
b. With holding the dose in the second stage of labor
c. Intrathecal placement of epidural catheter for reducing the incidence of PDPH in the
event of inadvertent dural puncture
d. Role of CT scans and MRI in detecting complications associated with neuraxial blocks
*MLAV: Minimal local anesthetic volume, MLAD: Minimal local anesthetic dose
Technical advances A review of the complications associated with CSE

has concluded that CSE is as safe a technique as a
Combined spinal epidural analgesia (CSEA) tech-
conventional epidural technique and is associated with
nique and low dose epidural regimes
greater patient satisfaction. There were no differences
With the evolution of sequential “needle-through- in maternal satisfaction, mode of delivery, ability to
needle” combined spinal epidural technique, it can be ambulate between CSEA and epidural techniques(17, 18).
used safely to provide labour analgesia. It combines Side effects and complications, however, can occur and
the rapid, reliable onset of profound analgesia result- includes pruritus, nausea and vomiting, hypotension,
ing from spinal injection with the flexibility and longer uterine hyper stimulation and fetal bradycardia and ma-
duration of epidural techniques (16). ternal respiratory depression. Fetal bradycardia is more
The CSEA kit spinal needle is fine pencil point pronounced with intrathecal sufentanil, perhaps due to
needle that comes with a locking device, which mini- its associated decrease in maternal catecholamines,
mizes post dural puncture headache and failed spinals. may precipitate uterine hyper tonicity and fetal bra-
Use of the spinal opioids provides immediate analgesia dycardia (19,20). However, several recent reports have
without producing any motor block, thus producing an found neither an increase in these complications nor
ambulatory block. The epidural catheter is activated increased cesarean section rate.
with low dose mixtures of opioid and local anesthetics; OAA (Obstetric Anaesthetists Association, UK)
hence, the ability to walk is not impaired. guidelines in 2005 (21) restrict the use of CSE as a rou-

tine and are indicated only in certain specific situations, Continuous epidural infusion of dilute local anes-
like very early stage of labour where local anesthetics thetic with opioid
are avoided, advanced stages of labour where rapid Continuous dilute low dose mixtures have been
analgesia is desirable and difficult epidurals, as CSEA, a major advance during the last few years. The dos-
reduces the failure rate of epidurals. ages recommended for labour analgesia is 0.0625%
Low dose epidural regimes bupivacaine with 2mcg / ml of fentanyl, infusing at 10-12
ml/Hr (28). Maternal and neonatal drug concentrations
With the emerging concept of low dose and have been tested and have been demonstrated to be
minimal local anesthetic dose and volumes (MLAD safe for both mother and neonate. These infusions
and MLAV), all present day labour epidurals are low have provided better pain relief but at the cost of more
dose epidurals. Traditionally, a high concentration numbness and motor blockade and more break through
(0.2% - 0.25%) of local anesthetic has been used to top-ups, thus the total dosage of local anesthetic is
maintain labour epidural analgesia. In the last decade, higher, when compared to PCEA or intermittent bolus
the concentration of local anesthetic used to main- methods.
tain labour epidural analgesia has been decreasing Patient controlled epidural analgesia (PCEA)
(0.0625% - 0.125%). The use of low concentration of
PCEA is a novel method of drug delivery system;
local anesthetic has reduced the total dose of local
provide several advantages, including the ability to
anesthetic used, as well as the side effects, such as reduce the drug dosage. Self-control and self-esteem
motor blockade (22, 23). may be vital for a positive experience in childbirth.
Using an up-down sequential allocation method, PCEA achieves both; thus, it is a useful alternative for
Gordon Lyons et al (24) in their comparative study s maintenance regime.
sought to determine the minimum local analgesic The ideal PCEA regimen is controversial. Lim
volume (MLAV) and minimum local analgesic dose and Cecelia et al (29) in their study demonstrated that,
(MLAD) of an initial bolus of epidural bupivacaine demand-only PCEA (5-mL bolus, 15-min lockout inter-
0.125% and 0.25%. MLAV of bupivacaine 0.125% was val) resulted in less local anesthetic consumption but
13.6 mL (95% CI 12.4–14.8) versus 9.2 mL (95% CI an increased incidence of breakthrough pain, higher
6.9–11.5) for bupivacaine 0.25% (P = 0.002). Hence, pain scores, shorter duration of effective analgesia,
and lower maternal satisfaction, when compared with
by reducing concentration, equivalent labor analgesia
PCEA with background infusion (5-mL bolus, 10–12-
was achieved with a significant reduction in dose of
min lockout interval, and 5–10 mL/h infusion)
bupivacaine. Such reductions in dose without compro-
mising analgesic efficacy provide a greater margin of Computer integrated PCEA (CI-PCEA)
safety and allow fine-tuning of labor analgesia. An RCT Lim et al. (30) reported another adaptation of epidu-
on combined obstetric mobile epidural trial (COMET) ral delivery pump technology. Their center has devel-
published in Lancet in 2001 by UK study group con- oped a computer-integrated PCEA system (CI-PCEA)
cluded that low-dose epidural analgesia resulted in that controls background infusion rates depending on
significantly more vaginal delivery (25, 26). the previous hour’s demand boluses. This randomized
trial compared a standard PCEA technique of 0.1%
Maintenance of intrapartum neuraxial analgesia ropivacaine with fentanyl administered as bolus-only
Maintenance of intrapartum analgesia is either by patient demand to the CI-PCEA technique that
done by intermittent manual boluses or through patient initiated an infusion algorithm with changing infusion
controlled or continuous epidural infusion pumps. Sev- rates depending on demand boluses. Despite patients
eral studies addressed technical aspects of neuraxial with the CI-PCEA technique receiving background
infusions, the hourly consumption of ropivacaine was
anesthetic delivery systems (27).

no different from that of the standard group. These were higher in those receiving levobupivacaine. Motor
studies illustrate that there is room for improvement block was greater with bupivacaine than with levobupi-
in administering epidural medication, especially for vacaine.
women with prolonged labors.
Alpha-2 agonist, clonidine and cholinesterase
Continuous spinal analgesia with micro catheters inhibitor, neostigmine have been used as adjuvants for
labour analgesia (33, 34). Both the drugs possess com-
The Food and Drug Administration (FDA) have
mon mechanism of action that can be beneficial. They
restricted use of spinal micro catheters due to an
can be administered either epidurally or via intrathecal
association with cauda equina syndrome. The FDA
route. Spinal clonidine, in doses of 100-200 mcg, pro-
authorized a large randomized, double-masked (31),
duces excellent labour analgesia of short duration, but
multicenteric study to evaluate the safety of continuous
at the cost of more sedation and hypotension. Spinal
intrathecal labor analgesia using a 28-gauge catheter
clonidine in doses of 50 mcg administered with bupiva-
versus continuous epidural labor analgesia. The results
caine, sufentanil mixture, significantly prolonged labour
of the trial were able to rule out the association of this
analgesia (197 compared to 137min) without producing
technique with neurologic injury. The study concluded
serious adverse effects. It has also been used with
that, providing intrathecal labor analgesia with sufen-
ropivacaine- fentanyl and was found to prolong the
tanil and bupivacaine via a 28-gauge catheter has an
duration. However the need of ephedrine requirement
incidence of neurologic complication less than 1%, and
was more in clonidine group. Also the fetal heart rate
produces better initial pain relief and higher maternal
abnormalities were more in the clonidine group.
satisfaction, but is associated with more technical dif-
ficulties and catheter failures compared with epidural Dewandre et al in their study 2010 (35), concluded
analgesia, also the CSA kit is more expensive, hence that, hypotension occurs more frequently when clo-
not routinely recommended. nidine is added to epidural ropivacaine instead of an
equi analgesic dose of sufentanil. Therefore, clonidine
There have been few studies using single shot
cannot be recommended for routine administration for
spinal analgesia using intrathecal morphine (300 to
labour epidural analgesia. Clonidine is not approved
400 mcg) with local anesthetic. The analgesia is not
for use in obstetric patients in the United States.
satisfactory during the advanced stage of labour and
incidence of nausea and pruritus are unacceptably Use of ultrasound to study neuraxial anatomy and
high, hence not routinely recommended. localize epidural space
Newer local anesthetics and adjuvants – clonidine Ultrasound imaging of the spine has recently been
and neostigmine proposed to facilitate identification of the epidural space
and predict difficult spine score, especially in women
The availability of newer local anesthetics like
with abnormal lumbosacral anatomy (scoliosis) and
ropivacaine and levobupivacaine have contributed to-
those who are obese. Jose Carvalho et al (36), in their
wards the increased maternal safety in terms of being
study, found a good level of success in the ultrasound-
less cardio toxic after an inadvertent intravenous injec-
determined insertion point, and very good agreement
tion. However, the dosage used for labour analgesia,
between ultrasound depth (UD) and needle depth (ND).
cardio toxicity is not a major issue. The recent study
They also concluded that proposed ultrasound single-
comparing these two drugs over bupivacaine, offers
screen method, using the transverse approach, can
no added advantage and five times more expensive to
be a reliable guide to facilitate labor epidural insertion.
that of bupivacaine. M. C. Atieńzar and Parlance (32)
Thus epidural failure rate can be minimized in patients
in their randomized study comparing levobupivacaine,
with difficult backs.
ropivacaine and bupivacaine with fentanyl for labour
analgesia, concluded that all three regimens were ef- Acoustic puncture assist device (APAD), acoustic
fective during first stage of labor although pain scores signal based identification of epidural space is also
known to reduce the learning curve.

Newer insights into myths & controversies After the above evidence and several other meta
analyzed studies: ACOG committee revised their
Increased rate of operative and instrumental deliv-
statement, no longer endorsing a delay and explicitly
ery: Is epidural the cause?
disavowing consideration of fear of increasing the risk
Cochrane Database Systemic trials have em- of cesarean delivery. ACOG and ASA (American Soci-
phasized that Epidural analgesia had no statistically ety of Anesthesiologists) have also jointly emphasized
significant impact on the risk of caesarean section. In that there is no need to wait arbitrarily till the cervical
two different meta-analyses of randomized trials, com- dilation has reached 4-5 cm and endorsed a statement
paring patients with and without epidural, caesarean that `Maternal request is a sufficient indication for pain
delivery was clearly not associated with epidural anal- relief in labour” (41).
gesia, which showed that there is no direct relationship
of epidural and increased caesarean section (38). Early vs. delayed pushing
Use of neuraxial analgesia, however, is known Delayed pushing has been advocated in parturients
to prolong the duration of labour on an average by an under neuraxial blockade. Passive descent should be
hour. The association of occipito posterior position, encouraged along with delayed and monitored pushing
augmentation with oxytocin and instrumental deliv- during birth, to safely and effectively increase spon-
ery is relatively higher in patients receiving epidural taneous vaginal births, decrease instrument-assisted
analgesia. However, use of low dose mixtures has deliveries, and shorten pushing time (42). The PEOPLE
reduced the overall incidence of these undesirable (Pushing Early or Pushing Late with Epidural) Study also
adverse effects. In a large randomized trial involving supported delayed pushing for a better outcome (43).
1,054 patients (Comparitive obstetric mobile epidural Withholding the epidural top up in the second
trial, COMET study), the introduction of a low dose of stage
epidural infusion was associated with a 25% decrease
in instrumental vaginal delivery (25). Many centers discontinue epidural analgesia late
in labour to improve a woman’s ability to push and
Timing of epidural during labour: Epidural taken reduce the rate of instrumental delivery. But in the
early vs. late randomized controlled trials of epidurals discontinued
Most observational studies shows higher rate of late in labour compared with continuation of the same
cesarean delivery when epidural is initiated early in epidural protocol until birth (462 participants) the
labour. The ACOG (ACOG Statement in 2000 – Evalua- reduction in instrumental delivery rate was not statisti-
tion of Cesarean Delivery)) had suggested that epidural cally significant(44). However, there was statistically
analgesia may be delayed until a cervical dilation of 4-5 significant increase in inadequate pain relief when the
cm is reached based on a study published by Thorp JA epidural was stopped (22% versus 6%, RR 3.68, 95%
et al (39) (A randomized, controlled, prospective trial. Am CI 1.99 to 6.80).
J Obstet Gynecoln1993, 169:851-858) and few other
Vaginal birth after cesarean and epidural
studies.
Task force guidelines 2007 jointly issued by ASA
However, the small degree of difference in cervical
and SOAP (Society of Obstetric Anesthesiologists and
dilation between early and late groups (approximately
perinatologists) recommends, neuraxial techniques
1 cm) is an important limitation of these trials. Wong
being offered to patients attempting vaginal birth after
et al (40), in their landmark RCT of nearly 750 primi-
previous cesarean delivery. For these patients, it is also
gravid women in early labour concluded no difference
appropriate to consider early placement of a neuraxial
in operative delivery of cesarean rates when neuraxial
catheter that can be used later for labor analgesia, or
analgesia was administered early in labour (2 cm) vs.
for anesthesia in the event of operative delivery.
a group where epidural analgesia was administered
late in labour (4-5 cm). Another study that used con- Epidural and breast-feeding
ventional epidural also had similar conclusions.

The effect of epidural analgesia on breastfeed- in case of inadvertent dural puncture reduces the inci-
ing continues to appear in the lay press, in part due to dence of PDPH. Studies have also shown prophylactic
conflicting reports in the scientific literature. Several use of parenteral cosyntropin (IV) after an unintentional
studies and trials failed to demonstrate significant wet tap helps in reducing the need for the epidural blood
association between epidural and lactation failure or patch. There have been few case reports of occipital
less successful breast-feeding attempts (45). Further nerve block that has helped in relieving PDPH. Epidu-
studies are needed in this area to assess the strength ral blood patch is still the gold standard in treatment
and impact of any association if any. of severe PDPH, when conservative measures fail,
however it has a risk for recurrent wet tap, repeat blood
Backache and epidural
patch, back ache, seizures etc. The clinicians need to
In two recent randomised trials, there were no understand its limitations and mandates documented
significant differences in the incidence of long-term back counseling as there are medico legal concerns as well!
pain between women who received epidural pain relief The treating anesthesiologist has to rule out other
and women who received other forms of pain relief (37). secondary serious causes of orthostatic postpartum
Maternal pyrexia and the newborn headache (46, 47).
Epidural analgesia in non obstetrical patients Advances in management and treatment of com-
is generally associated with slight decrease in body plications following neuraxial blocks
temperature secondary to peripheral vasodilation Lipid rescue for treating local anesthetic toxicity
and redistribution of heat from core to periphery. In after an inadvertent intravenous injection was a new
contrast, observational and randomized studies in discovery. Weinberg et al in their animal study model
obstetric patients demonstrate that epidural analgesia published in anesthesiology in 2008 concluded that all
during labour is associated with maternal pyrexia and the metrics of resuscitation were much better with lipid
increased neonatal sepsis workup. The exact cause of infusion, which chelates bupivacaine from systemic
maternal pyrexia is not known. The temperature rise circulation effectively and stabilizes hemodynamics
generally is never above 1 0C with epidural, sometimes better, compared to that epinephrine (Anesthesiology
observed in women with long labours. Always rule 2008; 108:907–13).
out and treat any underlying cause if the temperature
Newer mechanisms of nerve injuries were studied
rise is more than 1 0C. Irrespective of the cause, any
by Claudio et al (Current concepts in anesthesiology,
pyrexia during the intrapartum period needs to be
Sept 2006), pressures generated during epidural injec-
aggressively treated with hydration, antipyretics and
tion were found tobe in the range of 15-20 psi, and in
other appropriate measures. Intrapartum pyrexia due
10% of patients, they were found to be around 30 psi.
to epidural does not warrant evaluation for neonatal
11psi is the break point for permanent nerve injury in
sepsis (45). Further studies are needed to determine the
case of intraneural nerve injections. Hence this was a
criteria for performing workups for sepsis in infants of
revelation that no injection or top-ups to be given when
low risk women who deliver infants at term.
the patient experiences pain or par aesthesia during
Postdural puncture headache (PDPH) injection, a very important risk management strategy.
The use of small-bore “atraumatic” spinal needles The infective complications (meningitis) following
will reduce the incidence of PDPH in patients receiving CSEA, which were reported high during initial obser-
CSE to approximately 1% or less. It was suggested vational studies, still remains inconclusive. Presently,
that the incidence of unintentional dural puncture is it is stated that infective complications are no more
less in CSE patients than in patients receiving conven- than what is being reported with other neuraxial tech-
tional epidurals as the spinal needle may be used for niques.
verification of correct placement of the epidural needle.
Insertion of epidural catheter more than 5cm inside the
Intrathecal placement of conventional epidural catheter

epidural space can cause knotting and looping of cath- should be in place. The practicing anesthesiologist
eters in the epidural space. Fluoroscopy or radiograph should practice and believe in holistic approach rather
may not be helpful in locating the catheter. Computed than concentrating only on neuraxial techniques!
tomography (CT) helps in locating the knotted or torn
epidural catheter. Literature reports a case of catheter
1. Cohen J. Doctor James Young Simpson, Rabbi Abra-
knot in the epidural space as well as a loop within the
ham De Sola, and Genesis, 1996. Chapter 3, verse
inter laminar ligamentum flavum between L3 and L4
16. Obstet Gynecol; 88:895-8
visualized by computed tomography (48).
2. Snow J. On administration of chloroform in during par-
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3. Penny P, MaryAnn O’Hara; 2002. Nonpharmaco-
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Weaning Stratergies for the Difficult
to Wean Patient 173 Palepu B Gopal
01 WEANING STRATERGIES FOR THE DIFFICULT TO WEAN PATIENT
Consultant, Critical Care Medicine, Palepu B Gopal

Apollo Health City & Axon Anesthesia Associates
Hyderabad
Mechanical ventilation is the definitive solution of Pathophysiology of failed or difficult weaning

first priority for respiratory failure of various etiologies.
Lung is pump, which fails when the work load
For every priority that we exercise, we pay a price as
which it endures to pump air, exceeds capacity of its
well. Out of all the complications that the patient faces
motors, which are respiratory muscles. This is true for
as a consequence of mechanical ventilation, probably
both spontaneous ventilation and during weaning from
the most worrisome is weaning failure. As soon as we
mechanical ventilation. This can happen due to various
decide to institute mechanical ventilation in a patient
reasons. There may be need for increase ventilation
and inform the relatives, the first question we face is
as in increased carbon dioxide production. Sometimes
whether he is going to come out of ventilator. Their
there is increased dead space, necessitating dispropor-
fears are not unfounded. About 15% of patients on
tionate ventilation. Neurological and metabolic condi-
mechanical ventilation experience difficulty to come
tions may result in increased respiratory drive. These
out of the same.
situations will increase work of breathing and result in
We are duty bound to answer this important ques- either ventilatory or respiratory failure.
tion from worried relatives. In this effort we are guided
Etiological illness necessitating critical care man-
by various trials and guidelines, which attempted to
agement and consequent complications, such as neu-
predict difficult weaning and solutions to this complex
romuscular deficit, poor nutritional status, pulmonary
problem. We have to be aware that we are weaning the
sequelae, cardiac status, hospital acquired infections,
patient, not the ventilator. For this the anesthesiologists,
fatigue, side effects of drugs and emotional and mental
pulmonologists and intensive care specialists need to
status, form a ready and unfortunate recipe of difficult
understand the physiological, pathological, mechanical,
weaning.
psychological and pharmacological factors influencing
difficult weaning and find scientific and evidence based Difficult weaning is nothing but continued respira-
solutions for this vexing problem. tory failure with all the aforementioned factors added.
All the principles of treating respiratory failure naturally
Neither ventilation nor weaning is a one man
apply in this situation as well. Among these, we need
process and one needs to develop a team approach
to identify reversible reasons for prolonged mechanical
along with nurses, respiratory therapists, nutritionists
ventilation, such as inadequate respiratory drive, inabil-
and pharmacologists to successfully wean-off a difficult
ity of the lungs to carry out gas exchange effectively,
patient from mechanical ventilation. The terms wean-
psychological dependency and inspiratory fatigue, and
ing, liberation and discontinuation have been variously
institute proven measures to overcome the same.
used to describe the process of freeing the patient from
ventilator.

Potential causes of weaning failure
Consequences of failed/delayed weaning

We clearly understand that mechanical ventilation such complications are not only prolonged by failed or
has complications such as ventilator associated lung delayed weaning, but new problems crop up as well.
injury (VILI), ventilator associated pneumonia (VAP), A failed weaning and extubation will subsequently lead
need for continued sedation, diaphragmatic fatigue, to reintubation of patients trachea, sometime in not so
thromboembolic episodes and gastrointestinal bleed- optimum circumstances. This will consequently prolong
ing. It is also well recognised that increased duration ICU and hospital stay with its financial implication and
of ventilation is associated with increased mortality. All also lead to increase morbidity and mortality. This has
been clearly shown in various studies as sited below:
Relationship between hospital mortality and time

between extubation and reintubation

Strategies to address weaning difficulties Difficult weaning: failure to tolerate the initial SBT
with a need upto three SBTs or upto seven days for
There are no magic formulae or modalities to man-
successful weaning.
age difficult weaning. Prevention is better than cure.
Preventing a weaning failure requires a periodic clinical Prolonged weaning: a failure of atleast three SBTs
follow up of the patient and a critical and continued and more than seven days for successful weaning.Upto
evaluation of patient’s readiness for weaning. Several 30% of patients have difficult or prolonged weaning with
indices and studies utilizing these indices are avail- consequent increase in mortality and morbidity.
able. Various strategies to deploy various measures to Unless there is evidence for clearly irreversible
optimize both the patient and ventilator modality have disease, a patient requiring prolonged ventilation
been proposed and studied. should not be considered permanently ventilator-
Reversible causes of weaning failure dependent until 3 months of weaning attempts have
failed.
There are several causes of weaning failure and
some solutions for the same. Increased ventilatory Readiness Testing
demand as suggested by minute volume above 15L/ This the process to identify that respiratory failure
min can be addressed by reducing CO2 production by has partially or completely resolved, respiratory muscle
suppressing fever, decreasing dead space, treating function has improved, and patient is possibly ready to
sepsis and reducing carbohydrate load. Increased air- breathe spontaneously. Two thirds of patients identified
way resistance (>15-20cm H2O) gives rise to increased with readiness testing tolerate weaning from ventilator
resistive load on the lungs. This can be reduced by successfully.
brochodilator or steroid adminstration, proper tracheal
Criteria used to determine readiness for trials of
toilet and placing appropriate sized endotracheal tube.
spontaneous breathing
The increased elastic load of lungs and chest wall is
suggested by decreasing compliance and clinical ex- 1. PaO2/FiO2 ratio -150 or SaO2 - 90% on FiO2 - 40%
amination including chest x-ray. Diuretics to decrease and PEEP 5 cm H2O
excess lung water, drainage of pleural fluid, gastric 2. Hemodynamic stability (no or low-dose vasopres-
decompression with NG tube and brochodilators will sor medications)
reduce the magnitude of elastic load. Neuromuscular
Additional Criteria (optional criteria)
incapacity as evidence by maximum inspiratory pres-
sures (MIP) of less than -20 to -30 cm H2O can be 1. Weaning parameters: respiratory rate - 35
treated by electrolyte correction, adequate nutrition and breaths/min, spontaneous tidal volume - 5 mL/
minimizing neuromuscular blocker usage. Reduced kg, negative inspiratory force -20 to -25 cm H2O,
ventilatory drive is indicated by unexplained hyper- f/Vt < 105.
capnia and reduced respiratory rate. Proper sedation
2. Hemoglobin 8–10 mg/dL
algorithm combined with correction of metabolic alkalo-
sis can alleviate this situation. Systematically following 3. Core temperature 38–38.5°C
these issues putting in a concerted clinical drill will go 4. Mental status - awake and alert or easily arous-
a long way in preventing difficult weaning situation. able
New stratification of weaning has been sug- Trial of spontaneous breathing
gested
Once readiness testing is positive, spontaneous
Simple weaning: Those who tolerate first spontane- breathing trial (SBT) has to be undertaken. SBT can
ous breathing trial (SBT) successfully and extubated be performed on pressure support (PS) < 7 mm Hg,
without difficulty. continuous positive airway pressure (CPAP) or through
a T-piece. Pressure support has been attributed with

counterbalancing the resistive workload offered by en- patients are ready to breathe on their own earlier than
dotracheal tube. Likewise CPAP can improve ventilator detected by conventional criteria. Patients randomized
triggering in presence of significant intrinsic PEEP. A to a daily awakening trial followed by an SBT (vs SBT
third modality, automatic tube compensation (ATC) alone) experienced increased time of mechanical ven-
has been introduced. ATC adjusts PS levels based on tilation, decreased time in coma, decreased ICU and
tube characteristics. Randomised control trials (RCT) hospital length of stay, and improved survival at1 year.
have compared PS to T-piece and showed all these Therefore, the improved outcome of combining a daily
techniques have equivalent efficacy in weaning. awakening trial and SBT resulted from patients being
awake and ready for extubation once they passed the
Spontaneous breathing trial protocol
SBT. Pro BNP, glucose levels and positive fluid bal-
Inform the patient regarding the process and his ance were some of the other factors which had positive
participation, that weaning is about to begin. Obtain influence on weaning outcome.
baseline value and monitor vital signs, respiratory
Signs of failing SBT
pattern, gas exchange, and ECG for any rhythm dis-
turbance. Ensure a calm atmosphere, avoid sedation. Objective criteria
With patient in recumbent position, connect patient
• SaO2 < 0.90 or PaO2 < 60 mm Hg on FiO2 >
to T-piece or PS or ATC, with PEEP, with adequate
0.40–0.50 or PaO2/FiO2 <150
flow. This process can last upto 2 hours. The criteria
to assess patient tolerance during SBTs are respira- • Increase in PaCO2 by >10 mm Hg or decrease
tory pattern, gas exchange, hemodynamic stability and in pH >0.10
patient comfort. The tolerance of SBTs lasting 30 to • Respiratory rate >35 breaths/min
120 minutes should prompt for ventilator discontinua-
• Heart rate>140 beats/min or an increase > 20%
tion and possible extubation. The SBT trial should be
of baseline
done on a daily basis for all ventilated patients.
• Systolic BP < 90 mm Hg or > 160 mm Hg or
One fifth to one third patients fail their initial trial.
change of > 20% from baseline
A thorough survey of reversible and irreversible factors
should be undertaken in such patients. Hypoxemia is an Subjective criteria
unusual cause for weaning failure, another underlying
• Signs of increased work of breathing, including
mechanism for failure should be sought. Depressed
thoracoabdominal paradox or excessive use of
central respiratory drive (over sedation, neurologic pro-
accessory respiratory muscles
cess) can delay weaning. Indeed, as a consequence of
capacity-load imbalance, patients with weaning failure • Other signs of distress such as diaphoresis or
usually manifest elevated respiratory drive, detected agitation
by an elevated airway occlusion pressure. Excessive Weaning predictors
load may be imposed by the endotracheal tube, heat
and moisture exchange devices, or the ventilator tub- Several weaning predictors have been suggested
ing and valves. Intrinsic factors are more commonly by various studies and in various literature sources.
responsible. Measurements of oxygenation and dead space, PaO2/
FiO2, PAO2/PaO2, dead space (Vd/Vt) estimation,
In a novel ABC trial (Awakening and Breathing simple tests of respiratory load and muscular capacity,
Controlled Trial), Girard et al successfully used SBT negative inspiratory force (maximal inspiratory pres-
screening criteria without including standard weaning sure), respiratory system compliance and resistance,
predictors. They used very liberal oxygenation criteria minute ventilation, maximal voluntary ventilation, vital
(oxygen saturation measured by pulse oximetry, > 88% capacity, respiratory frequency, tidal volume, tests that
on FiO2 <0.5; PEEP < 8 cm H2O) finding that > 50% integrate more than one measurement, f/Vt, esopha-
tolerated the resulting SBT, strongly indicating that geal pressure measurements, calculating oxygen cost

of breathing, work of breathing, measuring gastric difficulty of COPD patients. The mode of SIMV with PS
intramucosal pH are some of these measures, none has been found superior to T-piece alone in weaning
of which have been proved superior to each other in of COPD patients resulting in shorter weaning period
various studies. Complex index calculations such as and reduced ventilator time.
CROP index (compliance, respiratory rate, oxygen-
There are various computer drive algorithmic
ation, pressure) have been validated in some RCTs.
protocols with closed loop systems in development,
One of the strongest predictors of successful weaning
which take into consideration factors like respiratory
was nurse: patient ratio in ICU.
rate, tidal volume and end tidal carbon dioxide and give
Modes of progressive weaning feed back to ventilator to either slow down or hasten
the process of weaning. There are limited preliminary
There has always been debate about the modes
studies supporting this type of approach.
of weaning, period of weaning and interval between
unsuccessful SBTs. There are no evidences to prove Various modalities such as volume support, vol-
that multiple SBTs are superior to single SBT per day. ume assured pressure support and adaptive support
One SBT fails it is strongly recommended that the ventilation have been studied and proved to be superior
patient should be given rest on ventilator mode with to existing modes by RCTs.
adequate support. Now the intensivist will be faced
Weaning protocols
with choice of another SBT or progressive weaning.
SIMV alone is not a good mode to wean the patient There are several protocols suggested for wean-
with prolonged ventilation. SIMV becomes effective in ing. The following is one of the widely followed such
giving muscle rest only when pressure support is added protocols:
to it. This is especially effective in cases of weaning

There have been several studies involving nurs- patient, pneumonia as cause for mechanical ventila-
ing and respiratory therapy teams utilising a protocol tion, higher severity of illness (APACHE II) at the time
based approach to weaning. There is no conclusive of extubation, use of continuous IV sedation, abnormal
evidence and agreement that protocol based approach mental status, delirium, semi recumbent positioning,
is superior to clinical judgement and flexibility and infrequent transport out of ICU for procedures, and im-
dividualized approach. proper physician and nurse staffing.
Non-invasive ventilation Various strategies have been proposed for pre-
venting extubation failure. ABG measurement at the
Several studies have proved the value of non-
end of SBT has not been proved effective predictor
invasive ventilation as an immediate adjunct to post
for successful extubation. Weaning predictors also
extubation after a difficult weaning. In an eligent study,
performed poorly in predicting extubation success.
Nava et al have studies the outcome of two hypercapnic
Cuff-leak test can be assessed by identifying an audible
respiratory failure groups who failed T-piece trial, one
air leak when the endotracheal tube balloon is deflated
with gradual pressure support weaning and other group
which can be quantified as the difference between the
with postextubation NIV support. The NIV group had
inspired and expired tidal volume during assist-control
significant reduction in duration of ventilation, length
ventilation. Some studies have demonstrated that
of ICU stay and 60-day survival. Another study found
systemic corticosteroids can reduce post extubation
in its interim analysis that NIV in the post-extubation
stridor, especially in high-risk patients. The ability to
period resulted in shorter ICU stay, shorter duration of
protect the airway also depends on cough strength and
ventilation, shorter hospital stay, fewer tracheostomies,
volume of respiratory secretions. Mental status is also
higher ICU survival and a lower incidence of nosoco-
important. NIV plays a role in modulating the post-
mial pneumonias and consequent sepsis episodes.
extubation status as well. While some RCTs support
Though a subsequent RCT did not confirm these
the positive influence of post-extubation RCT in high
results, a meta analysis of five studies did support the
risk extubations, there is lack of unanimous acceptance
use of NIV in difficult weaning situation especially in
to this modality. Lastly, good mental status and lack
COPD patients.
of delirium play a very important role in preventing
Sedation protocols reintubation.
There is good evidence that proper sedation proto- Tracheostomy
col leading to decrease in sedation also decreases the
Tracheostomy should be considered in patients
length of ventilation. Over sedation should be avoided
requiring prolonged MV. Tracheostomy may benefit the
by limiting the use of continuous infusions, utilizing
patient to reduce level of sedation, lower the resistance
sedation assessment scoring and daily cessation of
and improve respiratory mechanics, derive psycho-
sedative infusions. In contrast, at least one study found
logical benefit by allowing him to eat, drink and com-
that a sedation protocol did not hasten weaning from
municate non-verbally. The tracheostomised patient’s
mechanical ventilation.
participation in physical therapy further enhances his
Extubation emotional status and aides in recovery.
The natural consequence of a successful weaning In conclusion, preventing factors giving rise to dif-
is extubation. About 10-15% of extubated patients fail ficult weaning situation is the key to this vexed problem.
weaning and will require reintubation within 24 – 72 If we consistently remember that it is patient whom we
hours. Reintubation increases mortality, prolongs ICU are weaning and not the ventilator, the focus returns to
and hospital stay and leads to longer acute care with the former. Individualization of various protocols along
consequent complication. We need to identify risk fac- with application of various modalities will reduce the
tors for extubation failure to avoid this situation. These load of non-weanable patients on the unit and pave
are medical, pediatric, geriatric or multidisciplinary ICU way for better outcomes.

Suggested Reading 3. Girard TD, Kress JP, Fuchs BD, et al. Effi cacy and
safety of a paired sedation and ventilator weaning
1. Boles JM, Bion J, Connors A. Weaning from mechani-
protocol for mechanically ventilated patients in intensive
cal ventilation. Eur. Respir J 2007;29: 1033 -1056
care (Awakening and Breathing Controlled trial): a ran-
2. MacIntyre NR, Cook DJ, Ely EW Jr. Evidence based domised controlled trial. Lancet 2008; 371:126–134
guidelines for weaning and discontinuing ventilatory
4. Trevisan CE, Vieira SR. Noninvasive mechanical venti-
support: a collective task force facilitated by ACCP,
lation may be useful in treating patients who fail wean-
AARC and ACCCM. Chest 2001;120(suppl): 375S
ing from invasive mechanical ventilation: a randomized
-395S
clinical trial. Crit Care 2008 Apr 17
5. Scott K Epstein. Weaning from mechanical ventilation.

ACCP Crit Care Med Brd Rev. 20th edition: 213-226

HOW I DO IT?


Anesthetic Management of a patient with
Subarachnoid Haemorrhage for Cerebral Aneurysm
Clipping 182 Grace Korula
01 ANESTHETIC MANAGEMENT OF A PATIENT WITH SUBARACHNOID

HAEMORRHAGE FOR CEREBRAL ANEURYSM CLIPPING
Prof & Head, Grace Korula

Neuroanesthesia,
CMCH, Vellore
Aneurysms are degenerative, acquired structures of consciousness. The spread of blood through the
that become progressively more common with aging. subarachnoid space causes headache, meningism,and
The most common age at presentation is the sixth subsequent development of hydrocephalus. Blood clots
decade. Aneurysms develop mostly at vascular bifur- and adhesions hinder the free spread of blood through
cations, because of the turbulent flow at such sites. the subarachnoid space, supporting the formation of
With an increase in the size of the aneurysm, wall intracerebral haematomas. The blood (by oxyhemoglo-
compliance decreases and tension increases render- bin and its breakdown products) in the subarachnoid
ing the aneurysm increasingly susceptible to rupture. space is likely to contribute to the aetiology of cerebral
In the absence of rupture, the aneurysm may grow in vasospasm. The amount and location of blood seem
size to 2 cm in diameter (giant aneurysm). The vast to correlate with the incidence of cerebral vasospasm.
majority of aneurysms (80–90%) are located in the The expanding mass effect of the haemorrhage and
anterior (carotid) circulation, the anterior and poste- the development of brain edema and hydrocephalus
rior communicating, and the middle cerebral artery. contribute to increase in ICP. Soon after SAH, ICP may
The remaining 10–20% are located in the posterior approach systemic blood pressure. This phase is of
(vertebro-basilar) circulation. The great majority of an- short duration (possibly only minutes) and thought to
eurysms are saccular, less than one inch in maximum be the limiting factor in further leakage of blood from
diameter. The necks of giant aneurysms with sizes the aneurysm.
up to 10cm are often thick and brittle so that clipping
Autoregulation of cerebral blood flow
is much less likely to be successful than with smaller
aneurysms. Fusiform aneurysms are elongate, cigar SAH is usually accompanied by a decrease in ce-
shaped arterial enlargements commonly associated rebral blood flow and cerebral metabolic rate. Cerebral
with severe atherosclerosis. Aneurysmal SAH carries autoregulation is frequently impaired. The degree of
a 30 day mortality rate of 45%. An estimated one-third impairment correlates with the neurological condition.
of survivors remain moderately to severely disabled. The combination of a shift in the cerebral autoregulation
The three main predictors of mortality and dependence curve to the right and cerebral vasospasm may cause
are impaired level of consciousness on admission, delayed cerebral ischemic deficits. This underlines the
advanced age, and large volumes of blood on initial importance of an adequate cerebral perfusion pressure
cranial computed tomography. in the overall management of SAH, and is an argument
against the liberal use of intraoperatively induced hy-
Pathophysiology
potension.
Since saccular aneurysms are by far the most
Cerebrovascular CO2 reactivity
common aneurysms, and since they are usually located
at vessel bifurcations in the subarachnoid space, it The reactivity of the cerebral vasculature to
follows that most hematomas following rupture are changes in arterial carbon dioxide tension is usually
located in the subarachnoid space. During rupture of preserved during SAH. CO2 reactivity becomes im-
the aneurysm, free communication exists between paired only in patients with poor neurological condition.
intra-arterial and subarachnoid spaces. The sudden Thus in most cases of SAH, hyperventilation would
increase in regional intracranial pressure (ICP) to a remain an option to treat increased intracranial pres-
level equal to that of systemic arterial pressure is the sure and cerebral blood volume temporarily.
cause of sudden onset of severe headache and loss

Biochemical and hematological changes

The most common abnormality after subarachnoid to standardize clinical assessment and to estimate the
hemorrhage is hyponatremia, which usually progresses prognosis. In general, the higher the clinical grade, the
after a few days and will be maximal a week or two more likely are cerebral vasospasm, elevated ICP,
following the bleeding. Clinical grading scales such impaired cerebral autoregulation, impaired vascular
as the one of Hunt and Hess (Table 1) or the World CO2 reactivity, cardiac arrhythmias and dysfunction,
federation of neurological surgeons (Table 2) are used hypovolemia, and hyponatremia.
Table 1. Hunt and Hess grading scale for SAH

Grade Clinical Presentation
I Asymptomatic or minimal headache & slight nuchal rigidity
II Moderate to severe headache, nuchal rigidity, no neurological deficit other than cranial
nerve palsy.
III Drowsiness, confusion, or mild focal deficit.
IV Stupor, moderate to severe hemiparesis, and possibly early decerebrate rigidity and
vegetative disturbances.
V Deep coma, decerebrate rigidity and moribund appearance.
Table 2. World Federation of Neurological Surgeons Grading Scale for Aneurismal SAH.
Grade GCS score Motor deficit
I 15 Absent
II 13 or 14 Absent
III 13 or 14 Present
IV 7 - 12 Present or absent
V 3-6 Present or absent
Major Complications of SAH hypomagnesaemia and ECG abnormalities. General

measures in the prophylaxis of cerebral vasospasm
The major complications of SAH include re-
include administration of nimodipine, mild sedation,
bleeding, cerebral vasospasm leading to immediate
positive fluid balance, and avoidance of hypotensive
and delayed cerebral ischemia, hydrocephalus, cardio-
episodes and hyponatraemia.
pulmonary dysfunction, and electrolyte disturbances.
Non-neurological complications of SAH (e.g. anaemia, Cranial CT without contrast is the initial diagnos-
hypertension, hypotension, hyperglycaemia, electrolyte tic tool in all cases of suspected SAH. As the findings
disorders, cardiac insufficiency, and arrhythmias) de- suggestive of SAH can be subtle, and as subarachnoid
velop in more than half of patients and adversely affect blood degrades quickly and is almost completely re-
outcome. absorbed within10 days of SAH, the CT needs to be
interpreted by an experienced Neuroradiologist as soon
Cerebral vasospasm
as possible after the onset of sudden severe headache,
Cerebral vasospasm usually develops 3- 12 days and immediately in case of impaired consciousness.
after SAH, lasts on average 2 weeks, and affects 60- 70 The amount of blood on a CT without contrast can be
% of patients with SAH. It frequently results in cerebral described by Fischer four point scale. It is the best
ischemia, and is the major cause of morbidity and predictor of cerebral vasospasm and overall patient
mortality after SAH. SAH is frequently accompanied outcome.
by hyponatremia, hypokalemia, hypocalcaemia, and

Table 3. Fisher grading scale of cranial computerized tomography (CCT)

Grade Findings on CCT
1 No subarachnoid blood detected
2 Diffuse or vertical layers <
╬ 1mm
3 Localized clot and/or vertical layer >1mm
4 Intracerebral or intraventricular clot with diffuse or no subarachnoid
hemorrhage.
Table 4. Initial investigations for suspected SAH.

Investigation Comment
Full blood count *R/o anemia and leucocytosis

Coagulation screen *R/o coagulopathy
Serum urea and electrolytes Hyponatremia, common after SAH
Serum glucose Hyperglycemia, associated with poor outcome
Serum magnesium Hypomagnesemia, common and associated with poor outcome after
SAH
Chest-x-ray *R/O pulmonary edema and aspiration
12- lead ECG ST- segment changes common after SAH,*R/o cardiac arrhythmias
and ischemia
Noncontrast *CCT As soon as possible (with in 24 hrs) after the onset of sudden severe
headache
Lumbar puncture If noncontrast **CCT is normal in case of suspected SAH
CT angiography If SAH confirmed by **CCT or lumbar puncture
*R/o, rule out; **CCT, cranial computerized tomography
Occlusion therapy of cerebral aneurysm Clipping of aneurysm

Occlusion of the aneurysm after SAH is usually Clipping of an unruptured aneurysm has been as-
attempted either surgically (‘clipping’) or endovascularly sociated with overall procedural morbidity and mortality
by detachable coils (‘coiling’). The decision on whether rates of 4.0–10.9% and 1.0–3.0%, respectively.
occlusion of the aneurysm is indicated is based on pa-
Perioperative anesthetic management
tient age, World Federation of Neurological Surgeons
grade, co-morbidity, SAH onset time, and the anatomy Preoperative evaluation
of the aneurysm. The main rationale for early interven- Clinical signs and lab investigations as described
tion is the prevention of re-bleeding and possibly a above is reviewed before surgery. Preoperative ECG
reduction in the incidence of cerebral vasospasm by changes suggestive of electrolyte disturbances or
the removal of blood from the subarachnoid space. All myocardial injury may be frequently found in patients.
ruptured aneurysms in patients with Hunt and Hess However, in most cases, urgent surgery is indicated
grades I–IV are generally treated within 72 h. and takes priority over additional preoperative cardiac
testing. It may be safest to consider any cardiac symp-

toms and ECG abnormalities as reflecting true cardiac Brain relaxation

damage, and to adjust the perioperative anesthetic
Optimal brain relaxation and reduction in brain
management accordingly
bulk help surgical exposure, reduce the forces required
Premedication for brain retraction, and facilitate clipping of the aneu-
As with all areas of anesthetic practice, pre- rysm. Both goals are usually achieved by providing
medication needs to be individualized. No drug can an adequate CPP, avoiding episodes of hypotension
be considered the drug of choice in all situations. The and hypertension, administering the appropriate
risk of an anxious patient becoming hypertensive (pos- anesthetic drugs at appropriate doses and concentra-
sibly causing the aneurysm to rupture) needs to be tions, and maintaining normoventilation and adequate
balanced against that of respiratory depression. The oxygenation. In addition, pharmacological treatment
decision for or against any premedication, the choices of increased ICP or brain swelling is achieved using
of the type and the dose of the premedication drug will mannitol in a dose of between 0.25 and 2 g/kg body
depend on clinical grade, ICP level, respiratory status, weight. Frusemide is an alternative to mannitol. It’s
co-morbidity, and chronic medication. Nimodipine mechanism of action in causing a decrease in ICP is
administered for prophylaxis or treatment of cerebral unrelated to its diuretic effect, but may include reduced
vasospasm and any infusion of a vasoactive drug ad- CSF formation, and water and ion movement across
ministered to maintain an adequate CPP need to be the blood–brain barrier. The therapeutic effect of a
continued uninterrupted. combination of mannitol and frusemide on ICP and
brain bulk is consistently larger and more prolonged
Monitoring
than that of either drug alone. However the combined
Standard monitoring usually includes 5-lead therapy can cause large losses of free water and elec-
ECG, continuous intra-arterial pressure, pulse oxim- trolytes. Thus, very close monitoring of intravascular
etry, capnography, urinary output, body temperature, volume, electrolytes, acid- base, and serum osmolality
and neuromuscular block. Central venous catheter is are required.
usually inserted for guidance of intravascular volume
and for the injection of potent cardiovascular drugs. Decreasing the volume of CSF using a lumbar
Elderly patients with clinically relevant co-morbidity subarachnoid or ventriculostomy catheter is an effec-
(particularly cardio-respiratory) and expected surgi- tive means of reducing brain bulk and may become
cal difficulties may require additional cardiovascular necessary to achieve satisfactory brain relaxation.
monitoring. ICP monitoring is particularly helpful in During and after placement of the catheter, extreme
the blood pressure management during induction of care must be taken to avoid acute drainage of a large
anesthesia and in the postoperative management volume of CSF leading to brain ‘sagging’. The trans-
of patients who remain unconscious after surgery. mural pressure gradient of the aneurysm may increase
Cortical somatosensory-evoked potential (SSEP) and abruptly causing re-bleed.
brainstem auditory-evoked potential (BAEP) can be Conduct of anesthesia
used to monitor cerebral function. SSEP monitoring
has mostly been used during aneurysm surgery in The principal goals of the anesthetic manage-
the territory of both anterior and posterior cerebral ment for aneurysm surgery include (1) control of the
circulation, whereas BAEP monitoring has been used transmural pressure gradient (TMPG) of the aneurysm,
during operations in the territory of the vertebral-basilar (2) preservation of adequate CPP and oxygen delivery,
circulation. Detection of cerebral ischemia by evoked (3) avoidance of large and sudden swings in ICP, (4)
potential monitoring may lead to adjustments in surgical providing conditions that allow optimal surgical expo-
technique (e.g. removal or replacement of a vascular sure with least brain retraction, and (5) allowing rapid
clip) and hemodynamic management (e.g. increasing awakening of the patient. The intensity of nonsurgical
blood pressure to augment collateral perfusion during and surgical stimuli varies tremendously throughout the
temporary or permanent vessel occlusion). procedure. Laryngoscopy, tracheal intubation, position-

ing of the patient, placement of the pin head-holder, to CO2 is mostly preserved with all anesthetic drugs.
and raising of the bone flap are highly stimulating As prolonged hyperventilation may cause cerebral
interventions. The resultant hemodynamic stimula- ischaemia, transient and moderate hyperventilation
tion can cause a dangerous increase in the TMPG of should only be considered in patients with increased
the aneurysm with the associated risk of rupture of ICP. It should not be routinely used to counteract the
the aneurysm. In contrast, little or no stimulus exists cerebro-vasodilatory effects of volatile anesthetics
once the dura is open, with the potential for hypoten- (including N2O). The benefits of increased, positive,
sion. Sufficient doses of hypnotics (thiopentone or end-expiratory pressure on respiratory function need to
propofol), opioids, non-depolarizing neuromuscular be carefully balanced against the risk of increased ce-
blocking agents and infiltration of the scalp with local rebral venous pressure and impaired cerebral venous
anesthetic at the sites of pin placement will suppress drainage secondary to the PEEP-induced increase in
an inordinate blood pressure response to the various central venous pressure. The resulting increase in ce-
interventions. If hypotension is present during optimal rebral blood volume is of particular concern in patients
depth of anesthesia and hypovolaemia is excluded, with decreased cerebral compliance and increased
vasoactive drugs should be administered to increase ICP. In such patients, PEEP should be used very re-
the blood pressure. strictively.
One practical approach is to aim for a moderate Temporary occlusion
(approximately 20%) initial reduction in baseline blood
A reduction in systemic arterial pressure de-
pressure during induction of anesthesia, administer
creases the TMPG of the aneurysm and thereby
drugs that abolish or blunt the hypertensive response
the wall stress of the aneurysm. This may facilitate
to laryngoscopy and tracheal intubation (e.g. esmolol,
preparation and clipping of the aneurysm, and help
labetalol, and preservative free i.v.lignocaine), and then
control bleeding should rupture of the aneurysm occur.
proceed with tracheal intubation. Yet another approach
However, induced systemic hypotension is no longer
is to try to balance the baseline risk of inadequate cere-
used routinely in clipping of aneurysms, because it may
bral perfusion against that of rupture of the aneurysm,
critically impair overall cerebral perfusion, especially in
based on the patient’s clinical grade. Usually, patients
the presence of hypovolaemia, and has been associ-
with clinical grades I and II have normal ICP and do
ated with adverse outcome and a higher incidence of
not exhibit acute ischaemic deficits. These patients
severe cerebral vasospasm. Local hypotension at the
can be expected to tolerate a >20% transient decrease
site of the aneurysm can be established by temporary
in CPP without becoming acutely ischaemic, thereby
clipping of the artery feeding the aneurysm. The dura-
considerably decreasing the risk of rupture of the an-
tion of temporary occlusion should not exceed 15–20
eurysm. In contrast, patients with poor clinical grades
min, because this is associated with a decrease in brain
often have increased ICP, decreased CPP, and signs
PO2 and an increase in brain PCO2, and seems to be
and symptoms of cerebral ischaemia. These patients
the critical threshold for the development of postopera-
are less likely to tolerate even transient episodes of
tive cerebral ischaemic events. During such temporary
hypotension, and the duration and the degree of hy-
clipping, blood pressure should be maintained at or
potension must be kept to a minimum. At the same
even slightly above baseline values to ensure adequate
time, the increased ICP decreases the TMPG of the
collateral blood flow. Close communication with the
aneurysm and, thus, partially protects the aneurysm
neurosurgeon is important, because with the removal of
from rupture. In these patients, it might be justified to
the temporary clip, the unsecured aneurysm is exposed
accept a slightly higher TMPG in exchange for reducing
to a high shear stress.
the higher risk of cerebral ischaemia.
Induced hypothermia
Respiratory management
The randomized, prospective International Hypo-
Usually, normoventilation is the goal. With the
thermia Aneurysm Trial did not find a beneficial effect of
possible exception of N2O, cerebrovascular reactivity
induced mild (330C) intraoperative hypothermia during Recovery

aneurysm surgery. In clinical practice, passive cooling
After surgery, patients should be responsive to
usually leads to some degree of hypothermia. It is tol-
verbal command as soon as possible to allow early
erated, as long as it does not interfere with immediate
neurological assessment and decisions regarding
postoperative extubation and awakening. If clipping
diagnostic (e.g. CT and angiography) and therapeutic
of a giant aneurysm (<2 cm in diameter) is planned
(e.g. initiation of treatment for cerebral vasospasm)
(especially when located close to the brainstem), use
interventions. Various anesthetic drug combinations at
of cardiopulmonary bypass, complete circulatory arrest,
various dosages allow reasonably rapid and smooth
and profound hypothermia (>220C) may be neces-
awakening. If emergence from anesthesia is unexpect-
sary.
edly delayed or a new neurological deficit is present
Intraoperative aneurysm rupture upon awakening, CT or angiography may be used to
rule out intracerebral haematoma or occlusion of a
Intraoperative aneurysm rupture carries a high
blood vessel. In some centres, radiological assessment
morbidity and mortality. It may occur at any time dur-
is part of standard intraoperative practice.
ing the procedure, associated mostly with an abrupt
increase in the TMPG of the aneurysm (as a conse- Definition of what constitutes an ‘adequate’
quence of either a sudden increase in blood pres- blood pressure range during and immediately after
sure or an abrupt decrease in ICP) or with surgical emergence from anesthesia is difficult and should be
manipulation. It is to be expected that rupture of an agreed upon between anesthetist and neurosurgeon. A
aneurysm with an open skull and dura carries a better 20–30% increase in blood pressure above preoperative
prognosis than a rupture occurring during induction of baseline values poses the risk of intracranial haemor-
anesthesia. The incidence of aneurysm rupture varies rhage and oedema. Such a degree of hypertension
with size and location of the aneurysm, and with surgi- should be prevented by the prophylactic administra-
cal experience. Frank intraoperative rupture occurred tion of the appropriate type and dose of analgesic,
in approximately 11% of patients with previously rup- anti-emetic, anti-shivering or anti-hypertensive drugs.
tured aneurysm (compared with an incidence of 1.2% In patients at increased risk of cerebral vasospasm, a
in previously unruptured aneurysms). The choice of 10–20% increase in blood pressure above preoperative
acute interventions will depend on the size of the leak/ baseline values may be of benefit. Patients with preop-
rupture, the completeness of the dissection of the an- erative Hunt and Hess grades III or IV or intraoperative
eurysm and thus the surgeon’s direct access to it, and complications should not be extubated immediately
the feasibility of temporary occlusion of blood vessels after operation. Critically ill patients frequently require
proximally and distally to the aneurysm. The primary intensive postoperative cardiopulmonary and general
hemodynamic goal during rupture of an aneurysm is supportive care. Early tracheotomy should be con-
maintenance of normovolaemia. Temporary occlusion sidered in stuporous or comatose patients with poor
of cerebral arteries proximal and distal to the aneurysm medium term prognosis. It can shorten the duration
is an effective means of gaining control over ruptured and decrease the depth of sedation, and it can hasten
aneurysms. The blood pressure management during weaning from mechanical ventilation, allowing earlier
rupture of an aneurysm is controversial. On the one neuro-rehabilitation.
hand, a transient decrease in MAP to 40–50 mm Hg
Post operative vasospasm
decreases wall shear stress, reduces bleeding, and
facilitates surgical orientation, exposure, and clipping. Triple – H therapy
On the other hand, in the presence of clinically relevant Triple-H therapy (hypertension, hypervolaemia,
blood loss, the combination of hypotension and hypo- and haemodilution) is usually started in patients with
volaemia may result in profound cerebral ischaemia. an increase in transcranial doppler velocities (as a
Thus, temporary vessel occlusion is the preferred reflection of cerebral vasospasm), the development
technique to gain control over a ruptured aneurysm. of neurological deficits, or both. The therapeutic goal

of triple-H therapy is to increase CBF, increase CPP, siologist. Successful management requires adequate
and improve the rheological blood characteristics. For knowledge of pathophysiology, complications of SAH
this purpose, systolic arterial pressure is increased (by and meticulous care in maintaining homeostasis and
administration of i.v. fluid or cardiovasoactive drugs) to adequate CPP throughout all phases of anesthesia
approximately 160–200 mm Hg in clipped aneurysms; and in the postoperative period.
central venous pressure is maintained at 8–12 mm Hg
References
(or pulmonary artery wedge pressure at 15–18 mm Hg);
and haematocrit is decreased to approximately 0.3– Al-Shahi R, White PM, Davenport RJ, Lindsay KW.
0.35. Most neurosurgeons consider triple-H therapy Subarachnoid haemorrhage. Br Med J 2006; 333:
contraindicated in patients with unclipped aneurysm. 235–40
Although triple-H therapy is regarded by some as the Bendok BR, Getch CC, Malisch TW, Batjer HH. Treat-
most effective treatment of cerebral vasospasm (be- ment of aneurismal subarachnoid hemorrhage. Semin
cause it reverses neurological symptoms associated Neurol 1998; 18: 521–31
with cerebral vasospasm in up to 70% of patients), its
Brisman JL, Song JK, Newell DW. Cerebral aneurysms.
efficacy in reducing the incidence of delayed ischae-
N Engl J Med 2006; 355: 928–39
mic neurological deficits and death after SAH remains
unproven; it does not seem to reduce the incidence Cottrell JE, Robustelli A, Post K, Turndorf H. Furo-
of delayed ischaemic neurological deficits, and it may semide- and mannitol-induced changes in intracranial
actually increase mortality pressure and serum osmolality and electrolytes. An-
esthesiology 1977; 47: 28–30
Conclusion
Bryce K Weir. Intracranial Aneurysms and A-V malfor-
Clipping of intracranial aneurysm is one of the
mations In Textbook of Neuroanesthesia, Ed Maurice
most challenging operations faced by a neuroanesthe-
s. Albin.

Anesthetic Management of a Jehovah’s Witness For
Redo Total Hip Replacement 189 J Balavenkatasubramanian
01 ANESTHETIC MANAGEMENT OF A JEHOVAH’S WITNESS

FOR REDO TOTAL HIP REPLACEMENT
Senior Consultant J Balavenkatasubramanian
Ganga Medical Centre & Hospital,
Coimbatore
“Jehovah” is a personal name and refers to the cated either due to loosening or infection of an existing
almighty God and Creator of the universe. This is total hip arthroplasty. The patient usually presents to
shown at Psalm 83:18, according to the King James the surgeon with pain and progressive difficulty with
version of the Bible: “That men may know that thou, ambulation. Pain is often due to loosening but oc-
whose name alone is JEHOVAH, art the most high casionally due to infection. Occasionally the patient
over all the earth.” can present with clinical signs of a septic joint or even
Introduction systemic bactremia and sepsis. Yet another indication
of revision THR is inward protrusion of the acetabular
Jehovah’s Witnesses is a millenarian restora- component into the pelvis.
tionist christian denomination with nontrinitarian beliefs
distinct from mainstream christianity. They refuse As anesthesiologist it is pertinent to discuss
military services and blood transfusion. Hence when with the surgeons the surgical plan Regardless of the
they present for a surgical procedure like total hip ar- cause, revision THR is technically more demanding
throplasty (THR), they pose a definite challenge. The to the surgeon than the initial replacement and hence
anticipated blood loss in redo THR is approximately involves more surgical time and more blood loss. This
1.5 to 2 litres. Hence perioperative strategies have to is especially true with cemented total hip, because the
be devised to adopt measures for blood conservation methylmethacrylate must be removed so that a new
in the intraoperative and postoperative period. cemented or porous coated non cemented femoral
component has a chance to get solid purchase to avoid
A total hip replacement is a surgical procedure
loosening. If the revision is to correct a fractured femur
whereby the diseased cartilage and bone of the hip
or pelvic protrusion of the acetabulum, the amount of
joint is surgically replaced with artificial materials. The
reconstruction will result in an even greater anticipated
normal hip joint is a ball and socket joint. The socket is a
blood loss.
“cup-shaped” bone of the pelvis called the acetabulum.
The ball is the head of the thigh bone (femur). Total Preoperative preparation
hip joint replacement involves surgical removal of the • Preoperative assessment: special emphasis on
diseased ball and socket and replacing them with a hemoglobin level and coagulation profile.
metal ball and stem inserted into the femur bone and
an artificial plastic cup socket. The metallic artificial ball • Preoperative medications: patients are started on
and stem are referred to as the “prosthesis”. Upon in- iron, folic acid and B12.
serting the prosthesis into the central core of the femur, • Preoperative omission of antiplatelets and anti-
it is fixed with a bony cement called methylmethacry- coagulant medications
late. Alternatively, a “cementless” prosthesis is used
which has microscopic pores that allow bony ingrowth • If preoperative hemoglobin is less than 10mgs%
from the normal femur into the prosthesis stem. This preoperative erythropoietin to be considered
“cementless” hip is felt to have a longer duration and is Preinduction preparation
considered especially for younger patients. In THR, the
• Antifibrinolytics: Our drug of choice is tranexamic
average blood loss is around 1 litre but it is considerably
acid 10mg/kg body weight just before induction.
more in revision THR.
Second dose of 10mg/kg repeated after 3 hours
In revision THR, the estimated loss would be and the third dose of 10mg/kg repeated after 3
around 2 litres or more. Revision THR is usually indi- hours.

• Intravenous paracetmol: 1gm administered at in- Anestheisa techniques

duction. This aids in decreasing the perioperative
The chosen anesthetic technique must allow for
opioid usage atleast by 40% and hence the side
long surgical duration. Only the best hip revision sur-
effects of the opioids.
geon can accomplish revision of both components of
• Intravenous ramosetron for PONV a total hip, including cement removal, within the time
constraint of a one shot spinal anesthesia with a long
• Intravenous dexamethasone 8mg both for PONV
acting local anesthetic agent such as bupivacaine.
and as a part of multimodal analgesia
Hence the following options have to be considered.
• Time out is practised pre induction where the The surgical duration might exceed 3 hours and the
patients identity and the side to be operated is patient profile should allow us to decide if we need to
confirmed. supplement GA as many of them might not tolerate
• Two 18 G cannula are inserted in peripheral lateral position for that long.
veins. • Combined spinal epidural anesthesia
• One multilumen central line placed • Hypotensive epidural anesthesia - Niegel Sher-
• Intra arterial line as we plan deliberate hypoten- rock Technique
sion in these patients • General anesthesia + epidural anesthesia
• Informed consent explaining about the conse- • General anesthesia + continuous femoral block
quences of the blood loss which would not be
• General anesthesia
replaced.
Combined spinal epidural anesthesia
• Intermittent pneumatic compression devise for
both the lower limbs. • My technique of choice - Needle through needle
• Online fluid warmer and blood warmer. Hypo- • Preferred level - L2-3
thermia enhances the oozing and hence the blood
• Local anesthetic - Bupivacaine/ Ropivacaine
loss.
• Adjuvant - Clonidine intrathecal - 15-30 micro-
Position
gram
The surgical approach to total hip arthroplasty
• Target MAP - 60mmHg
starts with the selection of the patients position and the
type of incision to be made. The choices range from The addition of intrathecal clonidine aids in de-
anterior approach involving osteotomy of the greater creasing the MAP to around 60mmHg which consider-
trochanter of femur to the posterior approach cross- ably decreases the amount of intra operative blood loss.
ing the gluteal mass and approaching the hip without The possible bradycardia that could occur could be
trochanteric osteotomy. The preferred position would readily treated. A very useful technique for Jehovah’s
be lateral. This would considerably decrease the intra- witness
operative blood loss. But while using the lateral position Hypotensive epidural anesthesia ( Niegel Sherrock
one of the most important role to the anesthesiologist Technique)
is to give a true lateral position and use various devices
Widely practised in North America Combined
to prevent side to side movement of the patient on the
spinal epidural anesthesia is administered. The level
table. Also the surgeon might seek our help to verify
of spinal block is checked. Following this epidural bo-
the true lateral position so as to avoid placing the new
lus local anesthetics are administered until the T1-4
femoral prosthesis in an anteverted position that would
spinal level is blocked. Intra-arterial line is placed.
be likely to dislocate if the patient’s back is not verti-
Noradrenaline drip at a concentration of 4 microgram/
cal.
ml is instituted. The target MAP is kept between 55 to

60mmHg. The noradrenaline drip and the epidural bo- would be very handy. We will reinfuse the washed
luses are titrated to keep the MAP at the desired level. packed cells to the patient. If cell salvage is used with
The greatest advantage of this technique is it produces devices that use heparin, the possibility of systemic
very minimal blood loss and gives a very clear surgical heparinisation must be evaluated, because not all
field, this aids in decreasing the duration of surgery and heparin is removed with washing. We need to monitor
also aids in the cement to set very well. the activated clotting time and if needed we use anti-
dote protamine.
General anesthesia+ epidural anesthesia
Surgical causes of intra operative challenge to
The advantage of GA in these patients is the com-
anesthesiologist
fort achieved as redo surgeries last for nearly 2 hours,
and patients develop shoulder pain of the dependent 1. In revision hip, the approach to the hip joint can
side. If GA is administered the agents of choice would be much difficult due to scarring
be either sevoflurane or desflurane or intravenous
2. Blood loss from raw bone surfaces can be profuse
anesthesia with propofol.
and continuous during cement removal
General anesthesia+ continuous femoral block
3. Fracture of femoral shaft can be a major event
Continuous femoral block provides excellent during cement removal from the femoral canal.
perioperative analgesia and in patients in whom there It greatly enhances the bleeding and the surgical
is difficulty in administering neuraxial block due to de- time owing to the need for repair of the fracture
generative changes of the spine, it would be a good of the femur with wires, cables and plates
alternative.
4. Loss of bone from the loosening and secondary
General anesthesia osteoporosis can necessitate a custom, long
–stem prosthesis, this procedure necessitates
In stand alone general anesthesia, it becomes
the use of more reaming and more cement and
imperative to decrease the MAP either with the aid
more blood loss
of the inhalational agents or use specific therapeutic
agents like vasodilators- nitroglycerine, nitroprusside 5. The potential for systemic absorption of methyl
or beta blockers. methacrylate monomer is much greater during
revision hip and can have a magnified systemic
Advantages of regional anesthesia in revision
effect is greater blood loss has left the patient
THR
hypovolemic.
1. Total blood loss is less, due to decrease blood
Post operative blood loss
pressure and local vasodilatation.
It is imperative to keep a close watch on the blood
2. Lower incidence of DVT, related to improved fi-
loss in the postoperative period especially in revision
brinolysis secondary to more rapid restoration to
THR as there is considerable blood lost in the first 24
preoperative levels of antithrombin III or improved
hours through the drainage tubes.
flow in venous circulation
Postoperative concerns
3. There is less incidence of acute cognitive dysfunc-
tion • Pain relief: Multimodal analgesia is the norm of
the day.
4. A better neutrophil activity
We use the following regimen:
Auto transfusion or cell savers
Intravenous Pracetamol 1 gram 6th hourly
Intra operative cell salvage would be ideal in
these patients provided they are not infected cases. If + intravenous morphine infusion, titrated/PCA
these patients accept cell salvage method this option

+ regional Analgesia- infusion either epidural or of blood from soft tissue bleeding. The bulk of this
continuous femoral bleeding will happen within the early postoperative
period.
+ pregabalin/ gabapentin
• We need to verify the integrity of the sciatic nerve
• DVT prophylaxsis: Intermittent pneumatic com-
as a priority, as sciatic nerve is just posterior to
pression device from zero hours to a minimum of 3
the bulk of the dissection.
days into the postoperative period. Low molecular
weight Heparin, our choice is enoxaparin 40mg Conclusion
sc od
Revision total hip arthroplasty in a Jehovah’s
• Blood loss: The majority of total hip replacement witness patient is a real challenge. However preopera-
procedures will involve the placement of a gravity tive optimisation, intra operative blood conservative
or vacuum assisted drainage device. The place- strategies, choosing surgical techniques that would
ment of the prosthesis greatly decreases blood decrease the blood loss and focussed postoperative
loss, however we can still expect 500 to 800 ml care would aid in the smooth conduct of a challenging
clinical scenario.

Perioperative acute pain management in infants
and children 193 Vrushali Ponde
01 PERIOPERATIVE ACUTE PAIN MANAGEMENT

IN INFANTS AND CHILDREN
Vrushali Ponde
Although pain management in neonates, infants Pharmacology

and children is undergoing an overhaul, multiple stud-
The World Federation of Societies of Anesthesi-
ies have suggested that pain in children continues to
ologists (WFSA) Analgesic Ladder has been developed
be under-treated post-operatively. Hence I personally
to treat acute pain. Initially, the pain can be expected
feel privileged to write on this in a hope that young
to be severe and may need controlling with strong
generations gets more conscious about pediatric pain
analgesics in combination with local anesthetic blocks
and gets an insight into the options notwithstanding the
and peripherally acting drugs.
environment in which they might practise.
The purpose of this write up is to inspire the
reader’s thoughts towards this subject, which is influ-
encing today’s pediatric anesthesia world over. This is
reflected the latest issue of pediatric anesthesia issue to
pediatric regional anesthesia. To treat pain it is impera-
tive to understand its intensity. There are numerous
pain score methods for assessment of postoperative
pain in children, One of the most standard scale used to
assess postoperative pain in children is given below
Children and infants postoperative pain scale
(CHIPPS) -The following behaviours are given scores Non-opioid analgesics Paracetamol
of 0 to 2 as indicators of the level of pain experi- NSAIDs, including COX-
2 inhibitors
enced: Gabapentin, pregabalin2
• Crying Weak opioids Codeine
Tramadol
• Facial expression Paracetamol combined
with codeine or tramadol
• Posture of the trunk Strong opioids Morphine
Diamorphine
• Posture of the legs Pethidine
• Motor restlessness Oxycodone
Adjuvants Ketamine
The scoring system can be found in: Buttner W, Clonidine
Finke W. Analysis of behavioural and physiological
parameters for the assessment of postoperative anal- Routes of administration
gesic demand in newborns, infants and young children:
Several routes of drug administration are available in
a comprehensive report on seven consecutive studies.
children:
Paediatr Anaesth 2000;10(3):303-18.
Oral and rectal routes are the most commonly used
Modalities of perioperative pain management in
children - Pharmacological Intravenous infusions
- Regional blocks

Epidural/peripheral nerve infusions • Adverse effect: Doses less than 150mg/kg/day

have only rarely been associated with hepato-
- Repeated doses
toxicity, but the use of maximum doses for more
- Continuous infusion by syringe-drivers, me- than 5 days is not recommended
chanical or electronic devices
• “Suppol” suppository:
- Patient controlled administration is also used
Available 80 mg and 170 mg
usually in children over 5-6 years old
20 mg/kg child dose
Sublingual transdermal or transmucosal routes
• Comments : Should be combined with NSAID
Wound infiltration
and/or opioids or loco-regional analgesia for
The subcutaneous route is also used for pain moderate to severe pain in children.
management, and is particularly important for provid-
NSAIDS
ing analgesia in patients with burns or in chronic and
terminally ill patients where veins are at a premium. This group of drugs act through their inhibition of
prostaglandin biosynthesis. They work by inhibition of
Intramuscular administration should be avoided,
the enzyme cyclo-oxygenase (COX), which have two
not only because of pain and the psychological impact
distinct isoforms: the constitutive isoform, COX-1, and
(sometimes children feel pain because of fear of the
the inducible isoform, COX-2. COX-1 activation leads
needle), but also because drug absorption and the
the production of prostacyclin, which when released
timing of clinical effect can be unpredictable.
by the endothelium is antithrombogenic and when re-
Non-opioid analgesics leased by the gastric mucosa is cytoprotective. COX-2,
Paracetamol / Acetaminophen: discovered 6 years ago, is induced by inflammatory
stimuli and cytokines in migratory and other cells. The
• Paracetamol has analgesic and antipyretic prop-
anti-inflammatory actions of NSAIDs are due to inhibi-
erties but little anti-inflammatory effect. It is well
tion of COX-2, whereas the unwanted side-effects, such
absorbed orally and is metabolised almost entirely
as irritation of the stomach lining, are due to inhibition
in the liver. It has few side effects in normal dos-
of COX-1. Drugs that have the highest COX-2 activity
age and is widely used for the treatment of minor
and a more favorable COX-2 : COX-1 activity ratio will
pain. It causes hepatotoxicity in overdosage by
have a potent anti-inflammatory activity with fewer side-
overloading the normal metabolic pathways with
effects than drugs with a less favorable COX-2 : COX-1
the formation of a toxic metabolite. This is a low
activity ratio. The identification of selective inhibitors of
potency analgesic when used alone but much
COX-2 will therefore lead to advances in therapy.
more effective in combination with NSAIDS and/
or opioids. Following are the drugs frequently used in pediatric
practice:
• Administration
• Ibuprofen is frequently chosen for mild to moder-
(i) Intravenous: Start 30 min before the end of
ate pain. It is available in a liquid form adminis-
surgery.
tered orally to younger children.
(ii) Oral administration as soon as possible.
On set of action: 30 to 60 min
• Duration: as long as required. maximum daily
Dose:1-6 months: 5 mg/kg qds,
doses as 60mg/kg/day in the neonatal period (15
mg/kg qds) 1-2 years: 50 mg tds or qid
• Plasma levels are very dependant on route of 2-7 years: 100 mg tds
administration, high initial doses being required >7 years: 200 mg tds
when it is given rectally.

Max dose 40 mg/kg/day ketorolac: 0.5mg/kg 6 hourly (only IV form)

Administration diclofenac: 1-2 mg/kg 6 hourly for maximum 4 days
Intravenous: administration should start at least 30-60 Comments: Can be added to the pre-medication.
min before the end of surgery. Can be used in association with paracetamol and/
or opioids or local regional analgesia for moderate to
Oral administration: should start as soon as possible.
severe pain.
Duration: 3-5 days.
Doses of analgesic agents in children
Suppositories (diclofenac 12.5 and 25 mg)
Doses of analgesic agents suitable for use in
Dosage examples (i) Conventional NSAIDs include: children are shown in
Drug Route
Diclofenac Oral, rectal 1 mg/kg/8h
Ibuprofen Oral 10 mg/kg/8h
Ketorolac IV / continuous infusion 0.5 mg/kg/8h
Rectal 40 mg/kg; followed
by 30 mg/kg/8h
Oral 20 mg/kg; followed

Paracetamol by 30 mg/kg/8h
Newborn, rectal 20 mg/kg and

30 mg/kg/12h
Newborn, oral 30 mg/kg and

20 mg/kg/8h
Opioid analgesic (ii) Intramuscular.

These drugs act at receptors within the central (iii) Oral administration as soon as possible - dose 1
nervous system. Initially three distinct receptor groups mg/kg qid
were described (mu, kappa and sigma) on the basis
Monitor pain, sedation, respiratory rate and side
of their binding characteristics. The opioid drugs have
effects.
differing affinities for these receptors and are described
by their receptor affinities. Thus morphine and related Comments: Tramadol reduces serotonin and norepi-
compounds are known as mu agonists. nephrine reuptake and is a weak opioid agonist. In
analgesic efficiency, 100 mg tramadol is equivalent to
Weak opioid - Tramadol
5-15 mg morphine
Administration:
(i) Intravenous: inject slowly (risk of high incidence
of nausea and vomiting).

Drug dose
Drug Dose
Newborn 0.02 mg/kg/8h
Morphine Newborn (for continuous infusion) 5-15 ȝg/kg/h
Children 0.05-0.1 mg/kg/6h
Children (for continuous infusion) 0-30 ȝg/kg/h
surgery 2-10 ȝg/kg
Fentanyl ICU 2-5 ȝg/kg/h
Oral transmucosal fentanyl 15-20 ȝg/kg
citrate lollipop
Remifentanil Surgery 0.5-1 ȝg/kg/min
ICU 0.1-0.05 ȝg/kg/min
Codeine: Mainly used in combination with 0.5-1 mg/ Benefits of regional blocks
kg/4h paracetamol (suppositories or syrup)
Pain relief
Note: Although pethidine and pentazocine (0.5mg/kg) Reduction in general anesthetic requirement
Might reduce neurotoxicity of general anesthetic
are available in India and still used to date, remifentanil
agents
is not yet a part of our opioid drugs. Reduced need for postoperative ventilatory support
Regional analgesia in children Physiological benefits
Positive impact on hormonal stress response
Themed issue ‘Pediatric Regional Anesthesia’ – Gastrointestinal function
starting 2012 with a bang! gives comprehensive read Reduction in intraoperative blood loss
about this subject. Host-defense mechanisms
Economics benefits
The benefits of regional analgesia for children
The choice of regional technique has to minimally
include safety, and efficacy with no increased risk when
invasive and maximally effective. The dictum is to go
compared with general anesthesia alone but requires
as peripheral as possible. For example, a penile block
technical expertise. Children should faster recovery,
instead of caudal epidural or a sciatic nerve block rather
shorter ICU stay, and reduced ventilator requirement
than a lumbar epidural for unilateral foot surgery.
when supplemented with regional anesthesia. The
spectrum of autonomic, hormonal, metabolic, immuno- Any regional technique that can be performed in
logic/inflammatory, and neurobehavioral consequenc- adults can be practised in a child.
es caused due to surgical stress can be decreased by The regional block procedures than can be per-
regional anesthesia. Hence every surgery performed formed in neonates, infants and adults are
in children could be and should be supplemented by
a regional block for the advantages it offers.

Regional procedure Age Modality

Central neuraxial blocks:
Caudal epidural Neonates Loss of resistance
Lumbar epidural Infants Nerve stimulation
Thoracic epidural Children Ultrasound guidance
Head face and neck blocks:
Supraorbital Infants Surface landmarks
Infraorbital Children Ultrasound guidance
Submental
Occipital nerve
Upper extremity blocks:
Interscalene Neonates(in exceptional Nerve stimulation
Subclavian perivascular situations e.g ischemia of hand) Ultrasound guidance
Infraclavicular Infants
axillary Children
Paravertebral block Neonates Nerve stimulation
Infants Ultrasound guidance
Children
Lower extremity:
Lumbar plexus blocks Infants Nerve stimulation
Femoral nerve block Children Ultrasound guidance
Sciatic block with different
approaches
Abdominal wall blocks Neonates
Infants Ultrasound guidance
Children
Local infiltration Neonates
Infants Under direct vision.
Children
Note: Almost all the single shot blocks can be con- Practical difficulties in perioperative pain man-
verted into continuous techniques agement in very small children remain, such as the
judgment of pain itself a primary care taker is helpful
With the introduction of ultrasound there has
at such occasions. Alas there are many other factors
been a definite resurgence of abdominal wall blocks
such as hunger, thirst, unfamiliar environment that
such as rectus sheath, ilioinguinal, iliohypogastric, and
could make a child uncomfortable in postoperative
transverse abdominal plane block in children. Newer
period, this experience could be made evangelizing
drugs such as clonidine and dexmedetomidine have
by incorporating bright walls, toys, drawing material
a role to play in perioperative pain management more
etc when possible.
as adjuvants rather than as a primary modality.
Pediatric anesthesia 22 (2012) 1–2, is an issue
dedicated to pediatric regional anesthesia and I urge
you all to read this without fail.

Principles and Practice of One Lung Anesthesia 198 Mukul Kapoor
01 PRINCIPLES AND PRACTICE OF ONE LUNG ANESTHESIA
Director Anesthesiology Mukul Kapoor

Pushpanjali Crosslay Hospital,
Ghaziabad
Thoracic Anesthesia has always been a chal- the majority of patients in clinical practice. However,
lenging sub-speciality. Till the advent of the concept in some patients, severe hypoxaemia may occur. OLV
of One Lung Ventilation (OLV) for lung isolation, se- is required for a number of thoracic procedures, such
cretion draining or retaining positions, like the Parry as lung, oesophageal, aortic, or mediastinal surgery.
Brown position, were resorted too. In 1936, Magill For successful management of OLV, it is important to
achieved bronchial blockade using a long tube with highlight factors affecting the outcome of these cases
an inflatable cuff at its distal end that was advanced ie the physiological effects of lateral decubitus position
alongside a single-lumen endotracheal tube. OLV re- for thoracic surgery, pain associated with a thoracic
mains one of the more challenging techniques of daily incision, trauma to the lung tissue and resection of
anesthetic practice. Today OLV is a safe technique in parts of lung (Fig 1).
Fig 1: Problems associated with Thoracic Anesthesia
Physiology of lateral decubitus position and one West described the normal distribution of ventilation
lung ventilation and gravity dependent perfusion in the lung. The dis-
tribution of ventilation/perfusion (V/Q) at the different
When the anesthetised patient is moved from
gravity related lung zones; referred to as West’s zones,
the supine to the lateral decubitus position, significant
vary as per the fig 2. The salient features of West’s
alterations in the matching of ventilation and perfusion
description are:
occur. A brief review of the changes in ventilation and
lung perfusion follows and is essential for the under- • Blood flow is determined by gravity and is greatest
standing of the perturbations seen with OLV. in dependent lung areas; spontaneous ventilation
goes mostly to dependent areas because of dia-
Normal distribution of ventilation/perfusion and
phragmatic activity, or if ventilation is controlled
ventilation-perfusion ratio: Regional pulmonary
goes to the areas of least resistance (usually
perfusion and ventilation are spatially heterogenous.
non-dependent segments)

• Though apical alveoli are largest (due to the trac-

tion and weight of lung parenchyma), in the upright
lung with spontaneous ventilation, both ventilation
and perfusion are greatest near the diaphragm;
thus they are reasonably well-matched
• Positive pressure ventilation tends to ventilate
non-dependent lung regions
• In supine position, or to a greater extent if supine
and paralyzed or anesthetised (lack of diaphrag-
matic activity), the weight of the abdominal con-
tents restricts ventilation of the bases
Fig 2: Zones of West

Ventilation and perfusion in lateral decubitus posi-
tion awake, chest closed, breathing spontaneously:
Blood flow and ventilation to the dependent lung are
greater than to the non-dependent lung. Thus the
dependent lung is similar to the dependent areas of
the upright lung (near the diaghragm) under normal
conditions (Fig 3).
Fig 3: Ventilation & Perfusion in decubitus position, closed chest, spontaneous breathing
Ventilation and perfusion in lateral, awake, breath- inadequate because of a serious V/Q mismatch. This
ing spontaneously, with an open chest: Complica- occurs because there is no impediment to essentially
tions of mediastinal shift and paradoxical breathing oc- all ventilation going to the non-dependent (open, “up”)
cur. If controlled, positive pressure ventilation through lung (Fig 4).
a standard ETT is used, oxygenation may still be

Fig 4: Ventilation and Perfusion in Lateral, awake, breathing spontaneously, with an open chest
Ventilation and perfusion in lateral decubitus posi- compliance) by mediastinum, cephalic movement of
tion, anesthetized, with a closed chest: Dependent the abdominal organs via the flaccid diaphragm and
lung continues to receive more perfusion than non- exaggerated flexed (jackknife) position, with or without
dependent lung. Ventilation if spontaneous will still be chest rolls to free the axillary contents. The nonde-
directed to the dependent lung; however, with the in- pendent lung moves from an initially high, flat position
duction of anesthesia and controlled ventilation, most of to the lower, steep part of the curve. This results in
the tidal volume (VT) will go to the non-dependent lung an improved compliance for the non-dependent lung.
(least resistance). Approximately 55% of VT is delivered Although the anesthetised state results in atelectasis
to the non-dependent lung. GA with paralysis results in and a net loss of total FRC, the nondependent lung’s
both lungs moving down on the pressure-volume curve FRC may actually increase in the lateral position to
compared with the awake state (Fig 5). The dependent approximately 1.5 that of the dependent lung. These
lung moves from an initial, favourable position on the are the major alterations determining the distribution
steep portion of the curve to a position on the lower, flat of ventilation in the anesthetized patient in the lateral
portion of the curve, implying a reduction in functional position. Although gravity may have an effect on the
residual capacity (FRC) and compliance. The change distribution of ventilation during spontaneous ventilation
is due to the dependent lung being compressed (with in the lateral decubitus position, it has no significant
loss of FRC) and its excursion limited (decrease in effect during positive pressure ventilation.
Fig 5: Ventilation and Perfusion in lateral decubitus position, anesthetized, with a closed chest

Ventilation and perfusion in lateral decubitus posi- est degree of V/Q mismatch. Collapsing one lung for
tion, anesthetized, paralyzed, chest open: Depen- surgery compounds the problem. These effects are
dent lung continues to receive more perfusion than the more pronounced in patients with non-diseased col-
non-dependent lung, but more ventilation goes to the lapsed lung eg carcinoma esophagus, thoracic aortic
non-dependent lung (Fig 6). This causes the great- surgery.
Fig 6: Ventilation and Perfusion in lateral decubitus position, anesthetized, paralyzed, chest open
Factors helping counter effects of decubitus posi- and can reduce blood flow upto 50% in absence
tion of inhibiting factors. Hypocapnia reduces HPV and
Certain physiological and surgical factors help thus normocapnia recommended. Secretions,
counter the ill effects of decubitus position. These ac- transudates, compression of non-ventilated lung
tive and passive mechanisms help minimize the V/Q create hypoxic areas & reduce shunting. Systemic
mismatch: vasodilators like inhalational anesthetics, NTG,
SNP, dobutamine, Ca antagonists and beta-2
• Surgical compression & retraction of the operated agonists, inhibit regional HPV. Systemic vasocon-
lung passively redirects blood by kinking pulmo- strictors like catecholamines, dopamine, ephed-
nary arteries rine and phenylepherine, constrict non-hypoxic
There is a 10% gravity dependant decrease in vessels preferentially and reduce redistribution
dependant lung perfusion in ventilated lung.
• Progressive atelectasis due to mechanical com- Techniques of separating the lungs

pression reduces perfusion of non-dependant OLV is generally accomplished in two different
lung ways. The first involves the use of a double lumen en-
• Situation of obligatory R-L trans-pulmonary shunt dobronchial tube (DLT). The second method involves
created with an increase in A-aDO2 blockade of a main-stem bronchus to allow lung col-
lapse distal to the occlusion (bronchial blockers).
• Hypoxic pulmonary vasoconstriction (HPV) in
non-ventilated lung is the major factor reducing • Double lumen endobronchial tubes (DLT)
effects of lung isolation. HPV is an autoregula- • Single lumen tube and endobronchial blocker
tory compensatory mechanism, which diverts
blood flow from an atelectatic lung by increasing • Integrated-torque control blocker (Univent
pulmonary vascular resistance. HPV however tube)
may not be important in severely diseased lung, • Stand alone blocker (Fogarty arterial em-
as blood is chronically shunted. HPV response bolectomy catheter)
is best seen when PA pressure is normal as the
• Hybrid wire-guided endobronchial Blocker
response is attenuated if PA pressure is high or
(Arndt endobronchial system)
low. HPV is maximum within 15 min of hypoxia

• Endobronchial intubation with single lumen • Tracheobronchial tree disruption especially over-
tube inflated bronchial cuff
Double lumen endobronchial tubes : Most widely Bronchial Blockers: Bronchial blockers are making
used means of achieving lung separation and one-lung a comeback. A blocker is effectively a balloon on a
ventilation. DLTs are preferred because they: suction catheter and is placed under direct or fibreop-
tic vision into the bronchus. The trachea is intubated
• require a lesser degree of skill to insert than bron-
with a single lumen tube and the blocker may pass
chial blockers or single-lumen bronchial tubes
within or outside the tracheal tube. When the blocker
• allow conversion back and forth from OLV to two- is inflated, that lung will not be ventilated. The ‘suction
lung ventilation catheter’ element passing to the tip allows the isolated
• allow suctioning of both lungs lung to deflate, or suctioning. A blocker might therefore
be used instead of a DLT in a patient, be used when
• allow CPAP to be applied to the non-dependent
it would be difficult to insert a DLT (difficult intubation
lung
or paediatric) or when the airway anatomy is not suit-
• Left sided DLTs are mostly used because of able for a DLT. A blocker may also allow continued
problems associated with proper positioning of inflation of one lobe of the operated lung, for example
right-sided DLT to ensure that right upper lobe is if placed in the right bronchus intermedius, will allow
well ventilated. In case clamping of left main bron- right upper lobe ventilation when the operation is on
chus is necessary (Lt Pneumonectomy), the DLT the lower lobe. Advantages and disadvantage of use of
cuffs are deflated and the DLT withdrawn into the bronchial blockers are highlighted as Table 1 while the
trachea and tracheal cuff reinflated so that both advantages and disadvantages of individual Bronchial
lumens ventilate the right lung. Left sided DLTs blockers are highlighted in Table 2. Levine has defined
are contraindicated only if the left main bronchus the characteristics of the ideal blocker as:
stenosed, distorted or infiltrated by tumour.
• A balloon shape to stabilise it in the bronchus
Contraindications to use of DLT with low pressure/high volume inflation charac-
teristics
• Carinal or proximal bronchial mainstem lesions
• Be flexible and easy to manipulate into main stem
• Full stomach
or lobar bronchus
• Small patients
• Have a channel for deflation and suction distal to
• Difficult upper airway anatomy balloon
• Critically ill (ie., can’t break PEEP) • Be adaptable for use internal or external to stan-
Complications of DLTs dard tracheal tube
• Traumatic larnygitis • Have a wide variety of sizes for adult and paedi-
atric use
Table 1: Advantages and Disadvantages of Bronchial Blockers
Advantages Disadvantages
Reusable bronchial blocker Use a bronchoscope to place the catheter (need skills)
For selective ventilation in children < 12 yrs Tend to dislodge during manipulation – with disastrous
consequences
Blocker balloon requires a high distending pressure,
easily slips out of the bronchus into the trachea,
obstructing ventilation and losing the seal between the
two lungs

Table 2: Advantages and disadvantages of various bronchial blockers
Device Advantage Disadvantage

Fogarty Critically ill intubated patients who Not designed as a bronchial
catheter require OLV blocker
Small bronchus No communicating channel
Nasotracheal intubation Difficult to seal an air leak with the
Tracheostomized patients who single-lumen endotracheal tube
require OLV connector
No guidewire device
Potential for inclusion in stapling
line
Torque Control Difficult airways requiring OLV 8.5–9.0 mm ID sizes tied fit to
Blocker Selective lobar blockade pass through vocal cords
Univent Tracheostomized patients requiring Enclosed channel of 2.0 mm (not
OLV enough lumen to aspirate
Rapid sequence induction that secretions)
requires OLV More expensive
Robotic (cardiac, thoracic or Potential for inclusion in the
oesophageal surgery) stapling line
Arndt blocker Critically ill intubated patients who Requires a large single lumen
require OLV endotracheal tube >7.5-mm ID
Selective lobar blockade Opening center channel of 1.4
Difficult airways and OLV (oral or mm (not enough to aspirate)
nasotracheal) Longer time to collapse the lung
Tracheostomized patients Potential for inclusion in the
Robotic (cardiac, thoracic, or stapling line
oesophageal surgery)
Fogarty arterial embolectomy catheter is a device the stapling line, especially when used as a selective
designed specifically as a vascular tool; however, it lobar blocker.
has been used successfully for bronchial blockade
to achieve lung isolation. Fogarty occlusion catheter
can be advanced through the lumen of a single-lumen
endotracheal tube and can be used as a rescue device
when difficulties to position a right- or left-sided DLT
are encountered in patients. By advancing the Fogarty
catheter inside the endobronchial or endotracheal lu-
men of a DLT, lung isolation can be obtained (Fig 7).
The disadvantages of the Fogarty occlusion catheter
are that it is made of natural rubber latex, which is con-
traindicated in patients with latex allergy; there is a no
communicating channel, therefore suction or oxygen
insufflation is not possible; there is a lack of guidewire
device; and air leak from the breathing circuit can be A-Fogarty catheter, B-proximal swivel elbow port for
a common problem, specifically when the Fogarty fibreoptic bronchoscope, C-bronchoscope swivel
catheter is placed inside the single lumen endotracheal connector to breathing circuit and D-9Fr sheath with
tube. However, this problem can be prevented when integral haemostasis valve and side port clamped off
the Fogarty is placed externally to the endotracheal
Fig 7: Fogarty Embolectomy catheter inside a 9 Fr
tube. Complications reported its use for OLV include
venous sheath passed through the swivel connec-
airway rupture by forced introduction of the Fogarty
tor of the endotracheal tube
with the stylet in place and potential for inclusion in

Single lumen endotracheal tube with enclosed

torque control bronchial blocker (Univent) In 1982,
Inoue et a1 introduced a single-lumen endotracheal
tube with incorporated bronchial blocker so that when
OLV is no longer needed the tube can be left in situ
(for postoperative mechanical ventilation). The Univent
and its newest version, the Torque Control Blocker
Univent (TCBU), have a shape similar to that of a stan-
dard endotracheal tube. Within the Univent, there is a
channel enclosing a moveable bronchial blocker that
can be used to block the left, the right or any specific
secondary bronchi. The enclosed bronchial blocker is
made of flexible non-latex material, and has a flexible
shaft (TCBU) easy to guide into a bronchus. It has a
high-pressure, low-volume cuff. The TCBU has two
compartments, a large lumen for air/oxygen passage
through the anesthesia breathing circuit, and a small
lumen in the middle of the enclosed and movable bron-
chial blocker. Conventional endotracheal tube place-
ment is performed, and then a fiberoptic bronchoscope
is passed and the enclosed bronchial blocker advanced
into the targeted bronchus ie the bronchus of the surgi-
cal side, where the lung collapse occurs. An advantage
of the Univent is its utility in patients in whom the airway
is considered difficult for direct laryngoscopy and dur- Fig 8: Univent Tube
ing unanticipated difficult endotracheal intubation. The Wire-guided endobronchial blocker (Arndt blocker)
Univent has been used in tracheostomy patients who is an independent bronchial blocker attached to a 7 or
require OLV and as a selective lobar blocker to improve 9F catheter available in 65 and 78cm lengths. Inner
oxygenation. The Univent tube has been effective with lumen of the catheter measures 1.4 mm in diameter.
different modalities of ventilation including jet ventilation Near the distal end of the catheter, there are side holes
during sleeve pneumonectomy. It can be converted (Murphy eye) incorporated to facilitate lung deflation. It
to a conventional single-lumen endotracheal tube by has a high volume, low-pressure cuff with an elliptical or
deflating and withdrawing the bronchial blocker. The spherical shape (Rt vs Lt). The inner lumen contains a
Univent tube is shown as Fig 8. Complications reported flexible nylon wire passing through the proximal to the
with its use are: distal end and which it exits as a small flexible wire-loop.
• Failure to achieve lung separation The wire-loop is coupled with the fiberoptic broncho-
scope and serves as a guide wire (Fig 9). Proper ETT
• Inclusion of the enclosed bronchial blocker into
should be used. For placing the endobronchial blocker
the stapling line
through the endotracheal tube a fiberoptic broncho-
• Inflation of bronchial blocker cuff near the tracheal scope is used and the wire-guide is looped to direct
lumen producing a respiratory arrest the blocker into a main stem bronchus. The fiberoptic
bronchoscope has to be advanced far enough so that
Development of severe hypoxemia with the po-
the Arndt blocker will enter the bronchus while it is
tential risk of negative-pressure pulmonary edema.
being advanced. Once the deflated cuff is below the
Malposition and dislodgement of the bronchial blocker
entrance of the bronchus, the fiberoptic bronchoscope
while turning the patient into decubitus position

is withdrawn. The cuff is fully inflated with 2–3 mL of Overcoming hypoxia during OLV
air, if selective lobar blockade is attempted and with
There is significant V/Q mismatching in the lateral
5–8 mL of air if total bronchial blockade is attempted.
decubitus position during two-lung ventilation. The
For right main-stem bronchus blockade, it can be ad-
cause of hypoxemia during OLV is due to an increase
vanced independent of the wire-loop, under fiberoptic
in the physiological shunt through both the ventilated
visualization. The wire-loop can then be withdrawn
and non-ventilated lungs. Although HPV is effective
to convert the 1.4-mm channel into a suction port to
at maintaining PaO2 when the volume of lung that is
expedite lung collapse.
atelectatic is intermediate (30%–70%), as occurs dur-
ing OLV, many factors attenuate the HPV response
during surgery. Onset of hypoxemia begins approxi-
mately 5-10 minutes after initiating OLV and reaches its
maximal level by 15 minutes. This corresponds to the
time it takes for the oxygen to be absorbed completely
from closed cavities when blood flow is sustained.
During OLV, the patients should be receiving
FiO2 of 0.95–1.0 (using 0.95 may decrease the amount
of absorption atelectasis in areas of low V/Q). Once
adequate oxygenation has been sustained beyond
the expected time for hypoxemia to develop (at least
15 minutes), lower levels of oxygen may be utilized,
guided by pulse oximetry and/or arterial blood gases.
The most common cause of hypoxemia seen in clinical
practice is a malpositioned DLT. When the saturation
begins to fall, the patient should be removed from the
ventilator and hand ventilation should be instituted for
better assessment of lung compliance. A decrease
in compliance may indicate that the tube has slipped
distally and occluded the upper lobe bronchus leading
to an increased shunt and desaturation. The position
of the tube should be assessed and repositioned by
FOB. Using the FOB, remove any secretions, another
common cause of desaturation. Other causes of hy-
poxemia during OLV that need to be ruled out include
Fig 9: Arndt Blocker with guide-wire looped over
a light plane of anesthesia and bronchospasm. Deep-
fibreoptic bronchoscope
ening the anesthetic and administering bronchodilator
Limitations and complications: therapy should help improve gas exchange. If any of
• Shearing of balloon when the blocker was re- the above is not identified as the cause of the hypoxae-
moved through the multi-port blocker side. mia, then therapies directed at reducing the increased
physiologic shunt. The options for treating hypoxaemia
• More prone to dislodgment after turning the patient
are summarized as Table 3. The principles of therapy
into a lateral position than TCBU
to manage hypoxia are based on:

Table 3: Options in treating hypoxaemia during OLV
• Large tidal volumes Traditionally, the ventilatory the level of intrinsic PEEP is high or if excessive
parameters used during OLV were the same as external PEEP is added. Compared with the tradi-
those used during two-lung ventilation. It was tional large VT and volume-controlled ventilation,
become a common practice to set the ventilator the application of small VT and PEEP through
to deliver 10–12 ml/kg during OLV and maintain pressure-controlled ventilation is associated with
minute ventilation by adjusting the respiratory a lower incidence of postoperative lung dysfunc-
rate. Optimal ventilation and oxygenation is VT tion and satisfactory gas exchange.
for OLV at 7 mL/kg with respiratory rate of 20
• CPAP to the non-ventilated, upper lung has
breaths per minute (respiratory rate is adjusted to
been shown to be an effective method of treating
maintain an EtCO2 of 30-40 mm Hg). In patients
hypoxaemia during OLV and is considered the
undergoing major pulmonary resection or pneu-
first-line therapy. CPAP of 10 cm H2O to the non-
monectomy, post-pneumonectomy pulmonary
ventilated lung, with zero end-expiratory pressure
edema (PPPE) may occur. Although the etiology
to the dependent lung, was the most effective
of PPPE is unknown barotrauma/volutrauma,
way of improving oxygenation and decreasing
complement activation, and cytokine activation/
shunt flow through the collapsed lung during OLV.
release have been postulated as causes of PPPE.
Oxygen insufflation of to the non-ventilated lung
In addition, the use of large tidal volumes (10 mL/
without pressure fails to improve oxygenation.
kg) has been associated with the development of
The method in which CPAP is applied to the non-
intrinsic PEEP that may not be recognized. This
dependent lung is to allow the non-dependent
could lead to over distension and lung injury if
lung to deflate from a tidal volume inflation us-

ing CPAP 2 cm H2O for 5 minutes followed by Who have low dependent lung volumes, the ap-
an increase of CPAP to 5 cm H2O. Low level of plication of PEEP has been shown to be beneficial.
CPAP is effective at improving hypoxemia without However, if PEEP is applied during OLV with large tidal
impairing surgical exposure more than 90% of volumes to the dependent lung, alveoli may become
the time when proper tube position is confirmed. over distended causing intra-alveolar vascular com-
CPAP may also improve hypoxemia by diverting pression and worsening V/Q mismatch. The presence
more blood flow to the ventilated lung (improving of intrinsic PEEP must be suspected in all patients dur-
V/Q) due to an increase in vascular resistance ing OLV. If the level of intrinsic PEEP is too high, which
in the non-ventilated lung. The breathing system may cause over distension of the lung and a reduction
required to deliver CPAP to the non-ventilated in cardiac output, therapies that may reduce it include
lung is shown as Fig 10. adjusting the ventilator (decrease in VT, respiratory
rate, and I:E time ratio), treating bronchospasm, clear-
• PEEP The application of PEEP to the dependent
ing secretions, or applying extrinsic PEEP.
lung is intended to restore FRC, recruit alveoli,
and improve gas exchange. Studies in which • Other techniques
dependent lung PEEP has been studied have
• When these maneuvers fail to improve oxy-
reported mixed results. Selective application of
genation, or when severe hypoxemia occurs,
PEEP to the dependent lung in patients
two-lung ventilation should be resumed and
manual ventilation started
• Intermittent reinflation of the nondependent
lung may be necessary to maintain adequate
oxygenation
• For patients undergoing a pneumonectomy,
the surgeon may clamp the pulmonary artery
to improve V/Q matching
• Differential lung CPAP / PEEP simultane-
ously
• High frequency jet ventilation to both lungs
• In patients with significant restrictive pul-
monary disease (preoperative FVC < 77%
predicted) pressure controlled ventilation is
superior to volume controlled ventilation (10
ml/kg)
New approaches
Modification of pulmonary blood flow during OLV:
Inhaled nitric oxide (iNO) is a potent, short acting
pulmonary vasodilator, which is supplied only to the
dependent ventilated lung during OLV and to regions
of high ventilation within that lung. It has been studied
in several studies and interestingly has little effect on
oxygenation except perhaps in those patients with a
Fig 10: Breathing System to deliver CPAP during low PaO2 pre-iNO treatment. Another agent, almitrine,
OLV an intravenously administered pulmonary vasoconstric-

tor, prevents or limits OLV induced decreases in PaO2. pneumonectomy, to prevent right heart failure and ill
Almitrine infusion, 8mcg/kg/min started at initiation of effects of AF.
OLV, reduces the fall in the arterial oxygen tension by
The overall mortality rate after pneumonectomy is
>50%. No changes in CO or PVR were seen with this
7-12% in large studies. The causes being pneumonia,
dose of almitrine.
sepsis, cardiac causes, DVT/PE etc. Combination of
Reducing post lung resection morbidity/mortality respiratory distress and hypoxemia, with diffuse shad-
owing on CXR in the absence of cardiac dysfunction,
15-40% patients develop an arrhythmia, usually
pneumonia, sepsis or aspiration in the post-op period
atrial fibrillation, on the second or third postop day. This
is indicative of post-resection pulmonary edema. This is
is more common in older patients and is associated with
more common and serious complication after pneumo-
a longer hospital stay and increased mortality. Factors
nectomy (2-4%), with a mortality >50%. The possible
associated with the development of AF are ischemic
mechanisms for its development are fluid overload,
changes on ECG, cardiac enlargement, abnormal
abnormal lymphatic drainage, increased capillary per-
preoperative exercise test, intra-operative hypoten-
meability and right ventricular dysfunction.
sion, post-operative pulmonary edema, right-sided
operation and pneumonectomy. It may be indicative To conclude, OLV is most frequently utilized to
of poor cardiovascular reserve. Avenues of research provide a quiet field for the performance of many dif-
are whether this represents sympathetic stimulation or ferent surgical procedures. In some patients, severe
raised pulmonary artery pressures. Relative sympa- hypoxemia may result, mandating the implementation
thetic stimulation may result from intra-operative dam- of special therapies to ensure adequate oxygenation.
age to parasympathetic pathways. Epidural analgesia The technique of management of OLV is based on
with bupivacaine is associated with lower incidence achieving a goal of maintaining adequate gas exchange
and duration of arrhythmia than morphine. A number and protecting the ventilated lung from potential over
of centers routinely administer digoxin, to patients post- distension and injury.

PRO AND CON


Third Space – The Fact 211 M Vasanthi
01 THIRD SPACE – THE FACT
Professor and HOD, M Vasanthi

Kilpauk Medical College,
Chennai
Introduction procedures or trauma. According to this traditional

interpretation, fluid trapped within the classical third
In humans, approximately 60% of the total body
space is lost permanently for extra-cellular exchange.
mass is water. The intracellular fluid comprises two-
In order to nevertheless maintain the functional extra-
thirds of the body water. The remaining one-third –
cellular volume (fECV), the traditional perioperative
about 15 l in the normal weighted adult – comprises
fluid excess was considered an inevitable therapeutic
the extracellular volume (ECV, namely 20% of the total
reaction by generations of anesthesiologists.
body mass) consisting of the plasma (about 3 l), the
interstitial space (about 12 l) and small amounts of the The physiologic basis: why does fluid stay within
so called transcellular fluids such as gastrointestinal the vasculature?
secretions, cerebrospinal fluid and ocular fluid. The
Two thirds of human body fluid is located in the
latter are considered to be anatomically separated and
intracellular compartment. The remaining extracel-
not in dynamic equilibrium with the interstitial space
lular space is divided into blood plasma and interstitial
and the plasma, in which water and small solutes can
space. Both compartments communicate across the
easily be exchanged. The ‘third space’, nothing more
vascular barrier to enable exchange of electrolytes and
than a perception so far, has functionally been allocated
nutriments as the basis for cell metabolism.
to this trans-cellular compartment.
The positive intravascular pressure continuously
The ‘third space’: the theory behind the story
forces blood toward the interstitial space. Under physi-
Previous works have systematically divided the ologic conditions, large molecules, such as proteins and
third space into anatomical and non-anatomical parts. colloids, cannot cross the barrier in relevant amounts,
Anatomical losses are considered to be pathological which is a necessity for the regular function of circula-
fluid accumulations within the interstitial space which, tion. Otherwise, the intravascular hydrostatic pressure
together with the plasma, forms the ‘functional’ extra- would lead to uncontrollable loss of fluid toward the
cellular volume (fECV). The physiological fluid shift interstitial space and disseminated tissue edema .
between the intravascular and interstitial space is
In 1896, Ernest Starling suggested an interstitial
considered to contain only small amounts of protein
colloid osmotic pressure far below the intravascular
and small molecules, limited by an intact vascular
pressure. The concentration gradient across the vas-
barrier. As long as it is quantitatively managed by the
cular barrier generates a flow, which is directed into
lymphatic system, a physiological shift does not cause
the vasculature and opposes the hydrostatic pressure
interstitial edema. An overload of the lymphatic system,
resulting in an only low filtration per unit of time.
for example, by high volumes of iatrogenic fluid, can
principally be resolved contemporarily through redistri- According to the Starling principle, only the en-
bution and urinary output. Non anatomical losses, by dothelial cell line is responsible for the vascular barrier
contrast, formally represent the classical third-space function. In a rat microvessel model, it has been shown
shift, a part of the extracellular space functionally and that the interstitial colloid osmotic pressure was nearly
anatomically separating from the rest. Therefore, these 70% to intravascular osmotic pressure without causing
fluids are considered to now be part of the ‘non-func- interstitial edema, which is in contrast to the Starling’s
tional’ extra-cellular volume (nfECV). This separation concept, suggesting an only minor role for the interstitial
is believed to be caused primarily by major surgical protein concentration.

The endothelial glycocalyx plays a pivotal role Third, iatrogenic hypervolemia can lead to glyco-
in this context. Every healthy vascular endothelium is calyx degradation and cause an extensive shift of fluid
coated by transmembrane syndecans and membrane- and proteins toward the tissue. The pathologic shift
bound glyicans containing heparan sulfate and chon- affects all intravenous fluids. Opposed to the common
droitin sulfate side chains, which together constitute believe that, in contrast to crystalloids, colloids would
the endothelial glycocalyx. Bound plasma proteins, stay within the vasculature, a volume-effect >90%
solubilized glycosaminoglycans, and hyaluronan are only when a tetra starch solution was infused titrated
loading the glycocalyx to the endothelial surface layer to the actual intravascular volume loss. Administered
(ESL), which is subject of a periodic constitution and as a bolus in a normovolemic patient, two thirds of
degradation. Under physiologic conditions, the ESL the infused volume left the vasculature immediately.
has a thickness of approximately 1 micrometre and Volume resuscitation with colloids obviously requires
binds approximately 800 ml of blood plasma, so plasma careful titration to current losses to avoid a remarkable
volume can be divided into a circulating and noncircu- protein shift toward the interstitial space. Based on the
lating part. Accordingly, the glycocalyx seems to act as double-barrier concept, hypoproteinemia even intensi-
a molecular filter, retaining proteins and increasing the fies a vascular barrier dysfunction and promotes tissue
oncotic pressure within the endothelial surface layer. A edema formation. Perioperative fluid shifting is reflected
small space between the anatomical vessel wall and the in clinical data published two decades ago. Lowell et
ESL remains nearly protein-free. Thus, fluid loss across al. showed a weight gain of more than 10% in >40% of
the vascular barrier is limited by an oncotic pressure patients admitted to the intensive care unit after major
gradient within the ESL. Starling’s classic principle was surgery. This increase of body weight, representing
therefore modified to the “double-barrier-concept” interstitial edema, correlated strongly with mortality.
in which not only the endothelial cell line but primarily
Dehydration or hypovolemia?
the endothelial surface layer constitutes the vascular
barrier. Dehydration, affecting primarily the extravas-
cular compartment, and acute hypovolemia are two
Types of fluid shifts
different diagnoses and deserve different therapeutic
Type 1, occurring always and even if the vascular considerations. Urine production and insensible per-
barrier is intact, represents the physiologic, almost spiration cause a loss of colloid-free fluid, which, due
protein-free shift out of the vasculature. Occasionally to redistribution between intravascular and extravas-
it emerges at pathologic amounts. cular space, does normally not impair the intravascular
compartment directly. Thus, the resulting dehydration
Type 2, the pathologic shift is caused by dysfunc-
has to be treated by refilling the extravascular space
tion of the vascular barrier.
and replacing further losses by crystalloid administra-
In contrast to type 1, fluid crossing the barrier tion . In contrast, acute hypovolemia at first affects the
contains proteins close to plasma concentration. This intravascular compartment.
shift has basically three reasons.
Because crystalloids distribute freely between
First,surgical manipulation increases capillary interstitial and intravascular space, they are not suitable
protein permeability excessively. Interstitial fluid raised for volume resuscitation in acute hypovolemia. Lost
approximately 10% during realization of an enteral colloids and proteins cause a decreased intravascular
anastomosis in a rabbit without any fluids being infused. oncotic pressure, which would be aggravated by ad-
Concomitant administration of 5 ml/kg of crystalloid ministration of colloid-free intravenous fluid and would
infusion even doubled this edema. enforce the formation of interstitial edema. Thus, fluids
Second, reperfusion injury and inflammatory that mainly remain within the vasculature and maintain
mediators compromise the vascular barrier. oncotic pressure are needed to treat acute loss of
plasma volume effectively: colloids.

Goals and strategies for perioperative volume cardiac output guided fluid management reduced hos-
replacement pital stay and lessened complication rate. Additionally,
interleukin-6 response was attenuated in a colorectal
In the past, various studies were published that
surgery study using a doppler-optimized goal-directed
favored individual concepts of perioperative volume
fluid management. It has reported a reduced time of
management strategies. Most of them originated from
mechanical ventilation and intensive care unit stay in
perioperative care and focused primarily on the treat-
cardiac surgery patients using the global end-diastolic
ment in the operating room. Of course, those strategies
volume index and cardiac output to manage volume
impact postoperative ICU treatment as well. “restrictive”
administration. The extravascular lung water index may
strategies were compared with “permissive” or “liberal”
be a useful tool for GDT, too, and is subject of current
ones. However, commonly accepted definitions of “re-
discussion. Furthermore, goal-directed fluid therapy
strictive” or “liberal” fluid strategies do not exist, mak-
reduces inflammation, morbidity, and mortality not only
ing those studies nearly incomparable. Investigators
in severe sepsis and septic shock, but also in patients
normally labeled their traditional standard fluid regimen
who undergo major surgery.
the “standard” group and compared it with their own
restrictive fluid administration model. “Liberal” in one Conclusions
study was already “restrictive” in the other trial and
Consolidated findings regarding the endothelial
fluid administration followed rigid schemas or differ-
surface layer led to a new comprehension of the vas-
ent goals. Additionally, endpoints of the given studies
cular barrier. Starling’s principle was adjusted to the
varied from postoperative vomiting, pain, or tissue
“double-barrier concept” and the mechanisms of ESL
oxygenation to bowel recovery time, which de facto
alteration in critically ill patients seem to play a major
rules out a comparison. One of the most cited stud-
role in tissue edema formation. Because glycocalyx
ies in this regard is the work of Brandstrup et al., who
diminution leads to an increased capillary permeabil-
demonstrated that perioperative fluid restriction (2740
ity, fluid loss toward the interstitial space, commonly
vs. 5388 ml) reduced the incidence of anastomotic
considered to be a loss toward the “third space,” is
leakage, pulmonary edema, pneumonia, and wound
one major consequence of ESL degradation. Studies
infection in 141 patients undergoing major colorectal
concerning fluid and volume therapy prove an adverse
surgery without increasing renal failure rate. Interest-
effect of tissue edema formation on organ function and
ingly, a closer look at the infusion protocol reveals a
mortality. Therefore, knowledge of the consequences
comparison between crystalloid versus colloid fluid
of infusing different types of crystalloids and colloids
administration. The restrictive group received mainly
during physiologic and pathologic states is necessary.
colloids, whereas the liberal group was treated exclu-
Furthermore, fluid and volume administration are two
sively with crystalloids. All of those studies have in
different therapies for two different diagnoses. Dehy-
common that no hemodynamic goals were set, which
dration resulting from urine loss, preoperative fasting,
is in contrast to the “goal-directed-therapy (GDT)
and insensible perspiration requires fluid administration
approach” known most prominently from the study by
primarily based on crystalloid infusions. Intravascular
Rivers et al., in which the authors used central venous
volume deficit, i.e., acute hypovolemia, resulting in a
pressure, mean arterial pressure, serum lactate, and
decreased cardiac output requires volume replace-
mixed venous oxygen saturation as goals to optimize
ment, where colloid administration appears meaningful,
the early treatment in septic patients.
although current clinical data are not finally consistent.
Further peri and postoperative studies in surgical The right amount of administered volume should be
patients underline the importance of “functional” hemo- titrated “goal directed” using a strategy based on
dynamic goals to improve patients’ outcome. In a meta- macro-hemodynamic parameters of flow and vol-
analysis encasing four prospective randomized trials, ume.

Third Space – A Fiction 214 Anand K
01 THIRD SPACE – A FICTION
Assistant Professor Anand K

SRM Medical College Hospital & Research Centre,
Chennai.
For a long time, investigations in perioperative Tracer-dilution techniques are based on the principle
fluid therapy focused mainly on the choice of fluid to of applying a known amount of a suitable tracer into
administer (colloid vs crystalloid) and later on the com- the scanned fluid compartment and measuring the
position of crystalloids. Perioperative fluid management concentration of the tracer within this compartment
involved administering liberal quantity of fluids to com- after an adequate equilibration interval. The volume
pensate for insensible perspiration, fasting and third can be calculated from the formula,
space losses. This resulted in extreme positive balance
Volume = Amount Added-Amount Lost / Measured
and such excess fluid accumulated interstitially. Nei-
Concentration.
ther pathophysiology nor clinical outcome of “liberal”
fluid therapy had been systematically investigated
until recently. The pathophysiology of the liberal fluid
therapy, overwhelming evidences accumulating from
numerous trials disproving third space are presented
in this article.
Evolution of concept of third space loss
In 1960’s, numerous trials were conducted in
dogs subjected to haemorrhage, which showed bet-
ter survival with liberal administration of fluids, far
exceeding blood loss. The concept of third space
losses was proposed at the same time to explain the
need for excessive fluids. The same concept was Fig.1. Composition of the body compartments
used in resuscitating wounded soldiers in Vietnam,
where better survival rate among patients treated with
excessive fluids served as indirect evidence to prove The results of estimation of fECV depends on
existence of third space1. No researches with proper 1) Type of tracers
methodologies were done then and same concept was
extended to surgical patients without solid evidence. Two different types of tracers are utilised in the
Recent evidences from well conducted clinical trials measurement of the ECV:
have documented side complications of hypervolemia • Organic tracers (Sucrose, Inulin)
as a result of iatrogenic overloading and this has lead
to questioning the very concept of third space. • Salts (82Br, 35SO4, 22Na, Thiocyanate)
The “third” space – Result of flawed clinical trials 2) Suitable equilibration interval
Classical third space losses have never been • A sample withdrawn before full equilibration
measured directly and actual location of the lost fluid is achieved will show a falsely high con-
remains unclear (Fig 1)2. The studies which postulated centration of the tracer and consequently a
third space losses quantified these losses by measur- falsely small volume of distribution.
ing functional extracellular volume (fECV) before and • The equilibration time is different for different
after surgery through tracer dilution techniques 3,4. tracers

• The equilibration time is changing with fluid Pathophysiology of third space losses
overload, hypovolemia and following sur-
Traditionally third space has been described as
gery.
functionally separated part of extracellular compart-
3) Sample methods ment which cannot be localized but primarily consumes
fluid in the perioperative context. It is currently no
The single sample method
more than a myth to explain the otherwise apparently
• In this method full equilibration should be unexplainable third space fluid shifting. The second
attained before sampling. view suggests sticking to scientifically proven fact that
• The volume of distribution is calculated from fluid shifts perioperatively from functional extracellular
the concentration in a single sample. compartment to interstitial space. The resultant inter-
stitial edema is a relevant and acknowledged clinical
The multiple sample method
problem, affecting patient outcome16. Fluid shifting can
• Sampling is continued until full equilibration be classified as physiological and pathological ones -
is achieved
• Physiological type I shifting represents
• The volume of distribution is calculated from protein free shift across an intact vascular
the observed individual equilibration curve. barrier, due to crystalloid hypervolemia.
Serious concerns have been raised over type of • Pathological type II shift is protein rich due
tracer used, sampling times and equilibration times to damage to vascular endothelium.
allowed in these trials5. The limitations of these tracers
Recent evidences, especially with respect to
are that bromide enters red blood cells and is excreted
endothelial glycocalyx, conclusively proves the above
in bile, whereas sulphate is bound to plasma compo-
fact.
nents and accumulates in the liver, in the kidneys or
during shock in muscular tissue. Equilibration times to Every healthy vascular endothelium is coated
measure fECV have been reported to be up to 3 h for on the luminal side by an endothelial glycocalyx (Fig
the sulphate and over 10 h for the bromide tracer6, 7. 2)17-19. The endothelial glycocalyx plays a major role in
An important prerequisite for using tracer kinetics for vascular barrier function, preventing leucocyte adhe-
volume measurements is a steady state concentra- sion, platelet aggregation, decreasing inflammation
tion, which is difficult in perioperative period. Also all and tissue edema. As per Starling’s principle, water
the studies claiming existence of third space used retention within vascular compartment is due to signifi-
sulphate tracer in combination with single sample or cant inward directed colloid oncotic pressure gradient
few samples after 20-30 min of equilibration8-11. This between intravascular and interstitial spaces. However
leads to erroneous estimation of high concentration of it has now been shown that the effective colloid oncotic
tracer in plasma, hence apparently contracted fECV. pressure difference opposing filtration was 70% of the
luminal osmotic pressure, although intravascular colloid
As expected, trials measuring fECV with mul-
osmotic pressure was equal to that of interstitial space.
tiple samples and longer equilibration times found an
Hence transcapillary fluid loss seems to be limited by
unchanged or increased fECV12-15. Hence data from
an oncotic pressure gradient across endothelial glyco-
properly conducted trials do not support existence of
calyx, a structure unknown to Starling. Therefore the
third space.
classic Starling’s law needs to be updated, keeping
endothelial glycocalyx in mind.

Organ system Complications

Cardiovascular system Myocardial ischemia, arrhythmia,
cardiac failure
Pulmonary system Decreased functional residual
capacity and diffusing capacity,
postoperative hypoxemia,
pneumonia, respiratory failure
Gastrointestinal system Gut edema, enteric nutritional
intolerance, prolonged ileus,
translocation of endotoxin or
bacteria leading to sepsis
Renal system Renal failure secondary to
abdominal compartment
syndrome
Coagulation Crystalloids – hypercoagulation
Fig 2: Electron microscopic picture of Colloids (Starch) - decrease in
coagulation
Endothelial glycocalyx
Tissue oxygenation Impaired wound healing,
An intact endothelial glycocalyx is mandatory for anastomotic leakage, paralytic
ileus
a functioning vascular barrier16.Ischemia, reperfusion
injury, proteases, tumor necrosis factor, atrial natriuretic In a landmark multicenter study, Brandstrup
peptide(ANP) can degrade endothelial glycocalyx. Sur- B et al investigated 141 patients undergoing major
gical stress can release these inflammatory mediators colorectal surgery. They demonstrated that periopera-
and iatrogenic acute hypervolemia can trigger release tive intravenous fluid restriction (mean 2740 vs. 5388
of ANP. ml) significantly reduced the incidence of major and
In order to prevent perioperative interstitial ede- minor complications, such as anastomotic leakage,
ma, it is critical to protect endothelial glycocalyx. As pulmonary edema, pneumonia and wound infec-
Anesthesiologists, we cannot do much about primary tion21. Nisanevic et al found decreased postoperative
damage by surgical trauma, but avoidance of iatrogenic morbidity, including a shortened hospital stay, under
acute hypervolemia to avoid type II fluid shifting is defi- a protocol-based, more restrictive fluid therapy. Their
nitely possible. Intentional prophylactic overloading to patient group was more heterogeneous, consisting of
prevent post induction hypotension should no longer be 152 patients scheduled for mixed abdominal surgery22.
considered state of the art, in light of above findings. Holte and Kehlet recently recommended avoiding fluid
overload in major surgical procedures as a conclusion
Merits of restrictive fluid therapy in perioperative
of a systematic review of 80 randomised clinical trials23.
period
Hence overwhelming evidence points towards com-
Current standard fluid therapy is not evidence plications of iatrogenic hypervolemia and disproving
based. The postoperative weight gain of 3 -7 kilograms the concept of third space losses.
noted in major surgeries represents a genuine fluid
Conclusion
overload. Various complications of iatrogenic fluid
overloading are tabulated below20 The classical third space is purely fictional and
current evidences do not support existence of such
an entity. The perioperative fluid shifting to interstitial
space due to iatrogenic hypervolemia is pathological
and should be avoided whenever possible. Since
perioperative fluid therapy has a direct bearing on
outcome, both hypovolemia and hypervolemia should
be avoided.

REFERENCES 13. Breckenridge IM, Digerness SB & Kirklin JW. Increased

extracellular fluid after open intracardiac operation.
1. Brandstrup B. Dry or wet-which is the best for your
Surgery Gynecology & Obstetrics 1970; 131: 53–56.
patient? SAJAA 2008;14(1):32-6.
14. Pacifico AD, Digerness S & Kirklin JW. Acute alterations
2. Brandstrup B. Fluid therapy for the surgical patient. Best
of body composition after open intracardiac operations.
Practice & Research. Clinical Anesthesiology 2006;
Circulation 1970; 41: 331–341.
20:265–283.
15. Kragelund E. Changes of the apparent 3HOH, 82Br,
3. Shires T, Williams J, Brown F: Acute change in extracel-
125I human albumin and 51Cr red blood cell dilution
lular fluids associated with major surgical procedures.
volumes before, during and after operation in human
An Surg 1961; 154: 803-10
subjects. Annals of Surgery 1970; 172: 116–124.
4. Roth E, Lax LC, Maloney JV: Ringer`s lactate solution
16. Jacob M, Chappell D, Rehm M. The third space – fact
and extracellular fluid volume in the surgical patient: A
or fiction? Best practice and research clinical Anesthe-
critical analysis. Ann Surg 1969; 169: 149-64.
siology 2003:23;145-157.
5. Brandstrup B, Svensen C, Engquist A. Hemorrhage and
17. Chappell D, Jacob M, Hofmann-Kiefer K et al. Hydro-
operation cause a contraction of the extracellular space
cortisone preserves the vascular barrier by protecting
needing replacement – evidence and implications? A
the endothelial glycocalyx. Anesthesiology 2007; 107:
systematic review. Surgery 2006; 139: 419–432.
776–784.
6. Newton WT, Pease HD & Butcher Jr. HR. Sodium and
18. Pries AR, Secomb TW & Gaehtgens P. The endothelial
sulfate distributions in dogs after hemorrhagic shock.
surface layer. Pflugers Archiv 2000; 440: 653–666.
Surgical Forum 1969; 20: 1–2.
19. Rehm M, Zahler S, Lotsch M et al. Endothelial glycoca-
7. Reid DJ. Intracellular and extracellular fluid volume
lyx as an additional barrier determining extravasation
during surgery. British Journal of Surgery 1968; 55:
of 6% hydroxyethyl starch or 5% albumin solutions in
594–596.
the coronary vascular bed. Anesthesiology 2004; 100:
8. Roberts JP, Roberts JD, Skinner C et al. Extracellular 1211–1223.
fluid deficit following operation and its correction with
20. Holte H,Sharrock N.E, Kehlet H. Pathophysiology and
Ringer’s lactate. A reassessment. Annals of Surgery
clinical implications of perioperative fluid excess. British
1985; 202: 1–8.
Journal of Anesthesia 2002: 89 (4): 622-32.
9. Carrico CJ, Coln CD, Lightfoot SA et al. Extracellular
21. Brandstrup B, Tonnesen H, Beier-Holgersen R et al.
fluid volume replacement in hemorrhagic shock. Surgi-
Effects of intravenous fluid restriction on postoperative
cal Forum 1963; 14: 10–12.
complications: Comparison of two perioperative fluid
10. Shires T, Coln D, Carrico J & Lightfoot S. Fluid therapy regimens: a randomized assessor-blinded multicenter
in hemorrhagic shock. Archives of Surgery 1964; 88: trial. Annals of Surgery 2003; 238: 641–648.
688–693.
22. Nisanevich V, Felsenstein I, Almogy G et al. Effect
11. Fukuda Y, Fujita T, Shibuya J & Albert SN. The of intraoperative fluid management on outcome after
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Anesthesia and Analgesia 1969; 48: 831–838.
23. Holte K & Kehlet H. Fluid therapy and surgical out-
12. Breckenridge IM, Digerness SB & Kirklin JW. Validity comes in elective surgery: a need for reassessment in
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Inhalational Induction of Anesthesia Is The Best
Method Of Induction In Children - Pro 218 Neerja Bhardwaj
01 INHALATIONAL INDUCTION OF ANESTHESIA IS THE BEST

METHOD OF INDUCTION IN CHILDREN - PRO
Professor Neerja Bhardwaj
PGIMER,
Chandigarh
Introduction of the child as in starting an IV line avoiding the

psychological trauma of fear of needles. The
Induction of anesthesia is one of the most impor-
technique of “inflating a balloon” is usually an
tant events of putting a child to sleep. The technique
interesting experience for most of the children
of induction – whether inhalational or intravenous,
especially if they are premedicated. While using
depends on individual preferences. However the ease
sevoflurane a child can be made to sit on OT table
of induction – stormy vs. peaceful and relaxed has a
or in lap or even lie down if he desires to do so.
bearing on the preference of child for future anesthesia
The time taken to make a child sleep is only 3 – 4
experience. Also the method of induction may have
breaths with use of 8% sevoflurane. The sight of
an impact on the generation of perioperative anxiety
the needle makes a child uncooperative 90% of
– a risk factor for negative personality changes in the
the time even if the skin is effectively anesthetized
postoperative period.
with EMLA cream. In addition EMLA cream appli-
An ideal induction should be painless, smooth, cation produces vasoconstriction making venous
quick, and friendly for patient and medical staff, easily cannulation difficult. Also removing the pain of
accepted by the child, safe, without causing cardio- cannulation does not eliminate the anticipated
respiratory instability and postoperative complications. fear of pain related to cannulation. Even if a child
Based on my more than 20 years of experience in the is willing for a single prick of an IV cannula can
field of anesthesia,I consider inhalational induction to you guarantee the subsequent painlessness when
be the best for children as it meets most of the points using an IV induction agent propofol even with
of an ideal induction agent. The inhalational agents use of IV lignocaine? This can make subsequent
available for pediatric use are halothane, sevoflurane anesthetic in children traumatic making him unco-
(most commonly used), isoflurane and desflurane com- operative.(2) Aguilera et al showed that the level of
pared to availability of only induction agents – propofol anxiety was higher during IV induction compared
and thiopentone. However since the introduction of to inhalational induction.(3) Using thiopentone is
sevoflurane, inhalational induction of anesthesia has painless but it is likely to prolong recovery espe-
become very safe, rapid and generally pleasant. The cially in short procedures. In addition securing an
various reasons for labeling inhalational induction with IV line is not always easy in a chubby child, cold
sevoflurane in children as perfect are: weather – vasoconstricted veins and in children
1) Inhalational anesthetics on their own satisfy the who have undergone multiple surgeries – difficult
four pillars of anesthesia. They induce loss of con- veins and thin veins.
sciousness with limited response to pain, confer 3) Sevoflurane is usually administered as 8% con-
amnesia, blunt reflex responses and potentiate centration, however it can be given incrementally
muscle relaxants. In contrast intravenous (IV) – observing its effect and making dose adjust-
anesthetics ensure a complete anesthetic by use ments. Also the effect is reversible when the agent
of different drugs with different pharmacokinetic is switched off. An IV induction agent is usually
and pharmacodynamic effects.(1) given as a bolus based on body weight, with the
2) Inhalational induction is a painless but a smelly result that once injected it cannot be retrieved.
technique. If a child says I don’t want an injection 4) Inhalational induction does not cause any adverse
and don’t want pain this is the technique which is reactions or they are very infrequent. Bradycar-
desirable. It does not require any physical restraint
dia and hypotension are common side effects of 8) Inhalational anesthetics are the primary induc-
induction agents but are more common with IV tion agents for children with normal and difficult
induction agents as they are injected rapidly un- airways, foreign body in the airway, epiglottitis,
like the incremental dose of inhalational agent. an anterior mediastinal mass and asthma. When
Therefore sevoflurane does not cause any car- combined with hyperventilation, inhalational an-
diorespiratory effect and its safety is supported by esthetics provide excellent conditions for neuro-
the peri-operatve cardiac arrest registry findings.(4) surgery. Intravenous induction without a muscle
Propofol has been implicated in cardiac arrest in relaxant may be used for some of these condi-
children and also is responsible for propofol infu- tions; it is not the preferred technique because of
sion syndrome after prolonged infusion in ICU.(5) risk of apnea. Inhalational induction is standard of
care for difficult airway because it can be used as
5) Delivery of inhalational anesthetics to the lungs
a single agent and capable of rapid emergence if
provides a rapid delivery of drug to the brain in
the airway at any point becomes difficult to man-
infants and children. The intravenous agents are
age.
diluted in the venous circulation before passing
through the heart to reach the brain and other ves- Side effects of inhalational agents
sel rich groups. Owing to this pharmacology the
1) Movement during IV cannulation after inhalational
induction is comparatively faster with inhalational
induction with sevoflurane occurs frequently. This
compared to IV agents.
is because of low blood solubility of sevoflurane
6) It is easy to estimate blood tension of inhalational and its less potency which makes induction a little
anesthetics noninvasively by measuring maximum less fast. This can be addressed by keeping high
deliverable concentrations from the vaporizer and concentration for some time along with nitrous
breath by breath measurement of the inspired oxide before attempting cannulation.(6)
and expired inhalational concentrations. On the
2) Sevoflurane causes epileptiform activity especially
other hand intravenous agents demonstrate
if combined with hyperventilation. The significance
excessive inter-individual variability and cannot
of this is unclear and no grand mal seizure has
be estimated. Also the depth of anesthesia can
been reported.(7,8)
be assessed during inhalational anesthesia by
measuring the end tidal partial pressure of the 3) Emergence delirium does tend to occur more
anesthetic, an indirect measure of the brain partial frequently with sevoflurane but even intravenous
pressure of the anesthetic. agent can produce delirium. Also the delirium is
self-resolving and not remembered by the child.
7) Recovery after inhalational anesthetics is rapid
It is not harmful to the child but distressing to the
because it depends solely on exhaling the anes-
parents. It can be prevented or treated with small
thetic and their metabolism does not contribute
dose of propofol, opioid, dexmedetomidine, or
significantly to their elimination. The end tidal
clonidine.(9,10)
anesthetic gas monitoring permits a breath-by-
breath progress of the speed of recovery after dis- 4) Postoperative nausea and vomiting (PONV)
continuing these anesthetics. However recovery occurs more frequently (20%) with inhalational
after intravenous agents depends on redistribution agents. This can be treated with dexamethasone
and hepatic degradation of the drugs which is or ondansetron.
much slower than exhalation of inhaled anesthet- Contraindications of inhalational anesthesia
ics which may be impaired in the presence of
In certain conditions inhalational agents are con-
some disease states. With propofol, the greater
traindicated. These include malignant hyperthermia,
the duration of administration, the greater is the
conditions requiring rapid sequence induction and
recovery time because of this metabolism.
congenital myopathies including central core disease,

Duchenne’s muscular dystrophy, Wernig–Hoffman 6) Schwartz D, Connelly NR, Gutta S et al. Early intra-
disease. venous cannulation in children during sevoflurane
induction. Pediatr Anesth 2004; 14: 820–4.
REFERENCES
7) Akeson J, Didriksson I. Convulsions on anesthetic
1) Lerman J, Johr M. Inhalational anesthesia vs total in-
induction with sevoflurane in young children. Acta
travenous anesthesia (TIVA) for pediatric anesthesia.
Anaesth Scand 2004; 48: 405–7.
Pediatr Anesth 2009; 19: 521 – 34.
8) Vakkuri A, Yli-Hankala A, Sarkela M et al. Sevoflurane
2) Zielinska M, Holtby H. Pro – con debate: intravenous vs
mask induction of anesthesia is associated with epilep-
inhalation induction of anesthesia in children. Pediatr
tiform EEG in children. Acta Anaesth Scand 2001; 45:
Anesth 2011; 21: 159 – 68.
805–9.
3) Aguilera I, Patel D, Meakin G et al. Perioperative
9) Cravero J, Surgenor S, Whalen K. Emergence agita-
anxiety and postoperative behavioural disturbances in
tion in paediatric patients after sevoflurane anesthesia
children undergoing intravenous or inhalation induction
and no surgery: a comparison with halothane. Paediatr
of anesthesia. Pediatr Anaesth 2003; 13: 501–7.
Anaesth 2000; 10: 419–24.
4) Bhananker SM, Ramamoorthy C, Geiduschek JM et
10) Sikich N, Lerman J. Development and psychometric
al. Anesthesia-related cardiac arrest in children: up-
evaluation of the pediatric anesthesia emergence
date from the Pediatric Perioperative Cardiac Arrest
delirium scale. Anesthesiology 2004; 100: 1138–45.
Registry. Anesth Analg 2007; 105: 344–50.
5) Kam PCA, Cardone D. Propofol infusion syndrome.

Anesthesia 2007; 62: 690–701.

Inhalational induction of Anesthesia is the Best
Method of Induction in Children - Con 221 Anju Grewal
01 INHALATIONAL INDUCTION OF ANESTHESIA IS THE BEST

METHOD OF INDUCTION IN CHILDREN - CON
Professor, Anju Grewal
Dayanand Medical College & Hospital,
Ludhiana
Introduction tempted. This is attributed to the reduced solubility

of sevoflurane in blood resulting in decreased speed
Children of all ages except neonates or infants
of induction of anesthesia with sevoflurane than with
< 3 months of age, get distressed with fear during
halothane.(4)
induction due to unfamiliar environment, or / and
parental separation, resulting in abnormal postopera- On the other hand pain during injection espe-
tive behavior and lifelong fears from anesthesia. The cially when using propofol can be severe. This can
ideal induction should be painless, smooth, quick, and be minimized by using topical anesthetic like EMLA,
friendly for both the child and medical staff. The induc- Ametop cream and LAT gel. EMLA cream has the
tion technique should be safe and not cause circulatory disadvantage of a long pre-application time (≥ 1 hr)
or respiratory instability, nor should it be associated and causes vasoconstriction which can make IV can-
with postoperative complications such as emergence nulation difficult in an already difficult patient subset.
delirium or postoperative behavioral disturbance.(1) Ametop offers advantage of shorter application time,
but the hyperemia caused by it, can be severe and few
The technique used depends on a number of
case of anaphylaxis has be reported. LAT gel offers
factors including the child’s developmental age, un-
a distinct advantage of shorter <30min of application
derstanding and ability to cooperate, and previous
times.(1,5-7)
experiences, the presence of a parent and the interac-
tion of these factors with the child’s underlying medical The pain of propofol injection can also be reduced
or surgical conditions. Other patient factors which can by use of lidocaine up to 1 ml of 1% solution – 0.05–0.1
affect the choice of induction method include a dif- ml/Kg followed by gentle squeezing a child’s limb just
ficult airway, full stomach, absence of available veins, above the point when a vein catheter is inserted.(8)
etc(2)
Current literature indicates that >60% children
In support of intravenous induction of anesthesia suffer from anxiety in the preoperative period mainly
due to fear of parental separation and unfamiliar envi-
A. Needle phobia vs fear of mask
ronment and therefore induction of anesthesia can be
Traditionally inhalational anesthesia has been the highly stressful for a majority of pediatric population.(1,9)
preferred technique, as a lot of emphasis has been laid The most important strategy is preoperative prepa-
on needle phobia among children, however children ration in order to reduce the anxiety and fear. Both
have an equal share of fears, both for needles and pharmacological and non-pharmacological methods
mask. should be employed. Pharmacological Methods include
use of midazolam (anxiolytic and amnesic effects), or
True fear or aversion of mask has been evidenced clonidine (sedative, anesthetic sparing, analgesic &
to be enhanced especially after multiple exposures to sympatholytic).(1,2)
inhalational induction of anesthesia. Przybylo et al.(3)
have presented eight children demonstrating a real Among the various non-pharmacological methods,
mask fear which developed even after one exposure parental presence during anesthesia induction remains
to inhalational induction of anesthesia. till date a contentious and controversial issue. On one
hand though it may assist during mask /intravenous
Moreover movement has been reported during induction of a small child, it can be detrimental if the
sevoflurane anesthesia when i.v. access was at-

parent themselves distract both anesthesiologists and emergence. Rapid onset of action is independent from
children due their own anxieties and fears. The level alveolar ventilation. At a given plasma concentration,
of anxiety of the parents has a significant impact on the hypnotic effects are rapidly obtained; and much
the child. Studies have observed persistent behavioral faster deepening of anesthesia is possible with propofol
problems lasting to 6 months after operation in children compared with an inhalational agent. Propofol Ke0 (the
with an anxious parent than a child with a calm parent, plasma–effect–site equilibration rate constant) is larger
while a previous study showed that presence of par- reflecting rapid transfer and equilibration with effector
ents with low anxiety trait decreases the anxiety level site thereby depicting rapid onset of action.(1,2,4,20)
of children at induction.(1,2,9-11) In a Cochrane Review
Recovery after brief anesthesia with TIVA may be
on non-pharmacological interventions for assisting the
as rapid , whereas recovery after prolonged anesthesia
induction of anesthesia in children, 5 of 8 published
with TIVA is likely much more protracted, when using
studies did not show any difference in anxiety or co-
propofol based regimes due to the pharmacokinetic
operation of children on entering the induction area or
profile of propofol in children.(1)
during induction. (1,12-16 )Hence only parents who partici-
pate actively to provide beneficial distraction are useful Postoperative agitation is common in preschool
during the induction process, however their presence children after sevoflurane, desflurane, and isoflurane
does not preclude use of premedication.(1,2) anesthesia. Parents often rate it as the most distress-
ing event and even may express concerns regarding
Use of clowns in preoperative or induction areas
presence of any neurological damage.21 Furthermore
has been found to allay anxiety, however it did delay
studies have shown higher incidence of postoperative
procedures and interfered in the relationship between
behavioral changes in children receiving sevoflurane
the child and medical personnel.(1,17)Other distracters
anesthesia.(1, 4, 22)
in the form of computers and videos, hypnosis, music,
or showing parents a short video demonstrating a pe- Emergence from propofol anesthesia is smooth
diatric mask induction have been observed to have a and devoid of any excitatory or seizure like activity.
positive influence on postoperative behavioral score Rather propofol is indicated for control of sevoflurane
of their children, but there are no equivalent studies induced postoperative agitation.
preparing the child for painless intravenous induction.
(1,2,18,19) D. Hemodynamic profile
B. Indications for intravenous induction Sudden hypotension, and bradycardia can oc-
cur, but can be avoided by careful titration using small
It is indicated in all age groups especially if a pre- increments. Apnea and arrhythmias occur after sevo-
viously established intravenous catheter is present, in flurane induction, particularly if a large concentration
those with potential cardiovascular instability, and those is administered after a midazolam premedication.(1, 4)
who need a rapid-sequence induction because of a full
stomach. Other indications of intravenous induction E. Airway
include epilepsy, child posted for neurosurgical pro-
Propofol has been found to be less irritating to
cedures with high risk of cerebral ischemia, malignant
the airways and results in a significantly decreased
hyperthermia, muscular dystrophy, Wernig–Hoffman
incidence of laryngospasm. Desflurane and Isoflurane
disease, absence of appropriate delivery systems like
have been associated with higher incidence of airway
remote peripheral locations as it is independent from
irritability (due to its pungent odor), breath-holding,
airway instrumentation.(1,2,4)
coughing, excessive salivation and laryngospasm.
C. Induction and emergence characteristics Apnea following propofol induction can be prevented
by careful titration, thereby preserving spontaneous
Intravenous anesthetics produce rapid and respiration.(1, 2,4)
smooth loss of consciousness with rapid and peaceful

F. Antiemetic properties derdosage or overdosage of intravenous agents

immediately. Furthermore, no mechanism avail-
Vomiting is a major cause of postoperative dis-
able to detect a disconnection in the i.v. line (1) or
comfort in children above the age of 2-3 years and
s.c. infiltration of intravenous agents.
rated by parents as the most relevant outcome criteria.
It is also one of the main reason for admission after 4. Dosing regimens for propofol are variable in
outpatient surgery.(1) children, with very large inter-individual blood
concentrations. Use of propofol in small neonates
Propofol has antiemetic activities even at very low
in the first few weeks of life is contraindicated.
doses and has been found to be effective in preventing
vomiting early after surgery.(23) Avoiding inhalational 5. Prolonged infusions of propofol are not recom-
agents is considered to be one of several options, or mended for the fear of development of PRIS
even the primary option for preventing postoperative (Propofol infusion syndrome). PRIS has been
vomiting.(1,2,4) reported after short-term sedation and after
anesthetics of 2½ and 6 h duration in children.
G. Special advantage in situations like head
Therefore careful vigilance is needed while keep-
trauma, spinal cord monitoring, rigid or flexible
ing the total dose low. Monitoring in form of blood
bronchoscopy
gases, lactate levels is also indicated if procedure
Propofol does not suppress evoked potentials, are exceeding >3hrs duration.
reduces brain metabolism and cerebral blood flow,
References
thereby allowing for an easier control of raised intracra-
nial pressure. Hence it is better suited for neurosurgical 1. Marzena Zielinska, Helen Holtby, Andrew Wolf.
procedures and spinal cord monitoring during such Pro–con debate: intravenous vs inhalation induc-
procedures.(1,2) tion of anesthesia in children. Pediatric Anesthe-
sia 2011; 21(2):159-168.
H. No theatre contamination
2. Ghazal EA, Mason LJ , Coté CJ. Preoperative
No concerns regarding workplace contamination
Evaluation, Premedication, and Induction of Anes-
as it is a non-pollutant to the theatre environment,
thesia. In: A Practice of Anesthesia for Infants and
whereas inhalational anesthetics have been implicated
Children . Coté CJ, Lerman J, Todres ID editors.
in depletion of ozone layer which is mainly attributed
Philadelphia, Saunders. 2009 :36-60
to nitrous oxide.(1)
3. Przybylo HJ, Tarbell SE, Stevenson GW. Mask
Few demerits of intravenous induction(1,2,4)
fear in children presenting for anesthesia: aver-
1. Higher levels of anxiety especially even after sion, phobia or both? Pediatr Anesth 2005; 15:
simple sighting of needles despite well local an- 366–370.
esthesia of IV cannulation site.
4. Lerman J, Johr M. Inhalational anesthesia vs
2. Hypotension, bradycardia and apnea which are total intravenous anesthesia (TIVA) for pediatric
seen with bolus doses of propofol can be avoided anesthesia. Pediatr Anesth 2009; 19: 521 – 34
by using small incremental titrated doses under
5. O’Brien L, Taddio A, Lyszkiewicz DA et al. A criti-
careful monitoring
cal review of the topical anesthetic amethocaine
3. Actual blood and brain concentrations of propofol (Ametop) for pediatric pain. Paediatr Drugs 2005;
(or any other drug) cannot be accurately measured 7: 41–54.
in real time noninvasively. Thus agent analysis is
6. Kemp C. LET gel effective for pain relief. AAP
not commercially available for i.v. drugs, therefore
News 1999; 15: 2.
we cannot be warned by any alarms about un-

7. O’Connor G, Mullarkey C. Topical anesthesia in of anesthesia in children. Evidence-Based Child

children: reducing the need for specialty referral. Health: A Cochrane Review Journal 2011; 6
Eur J Emerg Med 2010; 17: 97–100 (1):71-134
8. Aitkenhead AR. Intravenous anesthetic agents. 17. Golan G, Tighe P, Dobija N et al. Clowns for the
In: Aitkenhead AR, Smith G, Rowbotham DJ, prevention anxiety in children: a randomized con-
eds. Textbook of Anesthesia, 5th edn. Churchill trolled trial. Pediatr Anesth 2009; 19: 262–266.
Livingstone: London, 2007: 34–51
18. Patel A, Schieble T, Davidson M et al. Distraction
9. Aydin T, Sahin L, Algin C et al. Do not mask the with a hand–held video game reduces pediatric
mask: use it as a premedicant. Pediatr Anesth preoperative anxiety. Pediatr Anesth 2006; 16:
2008; 18: 107–112. 1019–1026.
10. Kain ZN, Mayes LC, Caldwell-Andrews AA et 19. McEwen A, Moorth C, Quantock C et al. The
al. Predicting which children benefit most from effect of videotaped preoperative information on
parental presence during induction of anesthesia. parental anxiety during anesthesia induction for
Pediatr Anesth 2006; 16: 627–634. elective pediatric procedures. Pediatr Anesth
2007; 17: 534–539
11. Bevan JC, Johnston C, Haig MJ et al. Preop-
erative parental anxiety predicts behavioral and 20. Jeleazcov C, Ihmsen H, Schmidt J et al. Phar-
emotional responses to induction of anesthesia macodynamic modelling of the bispectral index
in children. Can J Anaesth 1990; 37: 177–182. response to propofol-based anesthesia during
general surgery in children. Br J Anaesth 2008;
12. Kain ZN, Mayes LC, Wang SM. Parental presence
100: 509–516.
during induction of anesthesia versus sedative
premedication: which intervention is more effec- 21. Mayer J, Bolt J, Rohm KD et al. Desflurane anes-
tive? Anesthesiology 1998; 89: 1147–1156. thesia after sevoflurane inhaled induction reduces
severity of emergence agitation in children under-
13. Kain ZN, Mayes L, Carmico L et al. Parental pres-
going minor ear nose-throat surgery compared
ence during induction of anesthesia: a random-
with sevoflurane induction and maintenance.
ized controlled trial. Anesthesiology 1996; 84:
Anesth Analg 2006; 102: 400–404.
1060–1067.
22. Bal N, Saricaoglu F, Uzun S et al. Perioperative
14. Kain ZN, Caldwell-Andrews AA, Mayes LC et al.
anxiety and postoperative behavioural distur-
Family-centered preparation for surgery improves
bances in children: comparison between induc-
preoperative outcomes in children: a random-
tion techniques. Eur J Anaesthesiol 2006; 23:
ized controlled trial. Anesthesiology 2007; 106:
470–475.
65–74.
23. Trame`r M, Moore A, McQuay H. Propofol anes-
15. Palermo TM, Tripi PA, Burgess F. Parental pres-
thesia and postoperative nausea and vomiting:
ence during anesthesia induction for outpatient
quantitative systematic review of randomized con-
surgery in infants. Paediatr Anaesth 2000; 10:
trolled studies. Br J Anaesth 1997; 78:247–255.
487–491.
24. Gan TJ, Meyer TA, Apfel CC et al. Society for
16. Peggy Yip, Philippa Middleton, Allan M Cyna,
ambulatory anesthesia guidelines for the man-
Alison V Carlyle. Cochrane Review: Non-pharma-
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cological interventions for assisting the induction
Anesth Analg 2007; 105: 1615–1628

Prone position surgeries can be done under
Neuraxial Block alone - Pro 225 Bhimeshwar M V
01 PRONE POSITION SURGERIES CAN BE DONE UNDER

NEURAXIAL BLOCK ALONE - PRO
Professor Bhimeshwar M V
Sarojini Devi Eye Hospital
Osmania Medical College
Hyderabad
Objectives of the presentation and reduced left ventricular compliance secondary to
increased thoracic pressure. Obstruction to the IVC
1. The effect of prone position on various systems
is also a known effect of the prone position and is ex-
and their implications in intra op period.
acerbated by the degree of abdominal compression,
2. Safety of regional anesthesia alone in prone posi- leading to decreased cardiac output and increased
tion. bleeding, venous stasis, and consequent thrombotic
3. The ease of resuscitation in case of adverse complications.
events and critical incidents. In addition to the above two physiological changes
Introduction of the prone position there is an increased sympa-
thetic response to change in position and anesthetic
The prone position of patients during anesthesia technique influences the degree to which such change
has been described used, and developed as a result occurs. Careful positioning is therefore essential to
of requirement to provide operative access for a wide minimize these risks.
variety of surgical procedures. In the prone position
the patient is positioned with the face downwards. Physiological effects on the respiratory system
This position is used in surgeries on the back, PCNL, Lung Volumes :
pilonidal sinuses, repair of tendo achilles and other
An increase in the FRC is a consistent finding
surgeries. However the prone position is associated
when a patient is moved from the supine to the prone
with predictable changes in physiology and also a
position. This is attributed to the reduction of the ce-
number of complications. In order to use the prone
phalad pressure on the diaphragm and reopening of
position safely it is mandatory that we understand
the atelectatic segments of the lung.
both the physiological effects and complications of the
prone position, anticipate the risks associated with this Distribution of pulmonary blood flow :
position, and minimize the complications. Providing an-
Though earlier studies demonstrated the redistri-
esthesia to a patient in prone position has always been
bution of pulmonary blood flow to dependant lung areas
debatable; though the scales were tilted more towards
when the patient were moved from supine to prone
general anesthesia, neuraxial block alone could be
position ; recent studies showed the regional perfusion
the anesthetic technique of choice, provided no other
is preferentially directed towards dorsal lung areas
contraindications for regional anesthesia exists in the
regardless of the position. Human studies showed the
patient.
uniform distribution of pulmonary blood flow in prone
Physiological effects of the prone position position. These studies also show that gravity has a
minimal role in determining regional blood flow.
Cardiovascular system
Distribution of ventilation:
The two most important physiological findings of
the prone position in the cardiovascular system are In the prone position there is an improvement in
reduction in the cardiac index (CI) and obstruction to the gas exchange due to redistribution of lung ventila-
the inferior vena cava. tion. Evidence suggests that pulmonary vascular and
bronchiolar architecture are more important than gravity
The reduction to the CI has been attributed to
in determining the ventilation and perfusion distribution
reduced venous return, direct effects on arterial fillings,
in supine and prone positions.

Complications associated with prone position prone position with the head rotated. This is probably
1. Injury to CNS: due to stretching of the salivary ducts leading to stasis
and acute swelling.
Injury to CNS is a catastrophic complication of the
prone position. These injuries could be due to arterial e) Shoulder dislocation:
occlusion; venous occlusion; air entrainment: cervical Shoulder dislocation can occur with prone posi-
spine injury or the effects of undiagnosed space oc- tion due to distribution of pressure. Isolated cases
cupying lesion. of shoulder joint pain have been reported in patients
2. Injury to peripheral nervous system : operated in prone position
Injury to peripheral nerves can occur in any posi- Indirect pressure injuries
tion due to nerve ischemia from undue stretching or
a) Macroglossia and oropharyngeal swelling:
direct pressure. It is sensible to assess the patient
ability to tolerate the proposed operative position while These are common occurrences in the prone
the patient is awake. position and the proposed mechanisms is excessive
flexion of the head and presence of a tracheal tube
3. Pressure injuries:
can cause kinking and obstruction of IJV in the neck
These occur as a result of application of pressure which in turn obstructs venous drainage from lingual
to dependent parts of the body. These pressure injuries and pharyngeal veins.
can either be direct or indirect (pressure or occlusion
of vascular supply). b) Mediastinal compression:
Direct pressure injuries This complication can occur in a patient with con-
genital anatomical abnormalities or after cardiothoracic
a) Pressure necrosis of the skin:
surgery.
This is a common cause of anesthesia related
c) Visceral ischemia:
injury which can occur in the prone position. Hence
close attention to positioning of the face, ears, breasts, Hepatic ischemia and pancreatitis have been
genitalia and other dependent areas to prevent pres- reported following prone position due to compression
sure sores or skin necrosis. Pressure injury is regarded on the abdominal organs.
as a recognized hazard.
d) Avascular necrosis of femoral head:
b) Contact dermatitis:
Is documented in patient undergoing surgery
Contact dermatitis of the face with periorbital in the prone position and is attributed to deliberate
and lip swelling after undergoing surgery with head
hypotension and increased venous pressure leading
placed in the prone positioner, which is made of flexible
to intraosseous hypertension and ischemia of femoral
polymethane foam to support the face during prone
head.
surgery by moulding around the eyes, nose and mouth,
was documented. e) Peripheral vessel occlusion:
c) Tracheal compression: The prone position can cause compression and
Tracheal compression can occur during surgery in occlusion of a number of peripheral vessels like axillary
the prone position, because of a reduced anteroposte- artery, external iliac artery etc.
rior diameter of the chest, which resulted in compres- f) Limb compartment syndrome and rhabdomy-
sion of the trachea between the spine and sternum. olysis:
d) Salivary gland swelling: Was documented in patients undergoing surgery
‘Anesthesia Mumps’ which is a bilateral painful in the prone position.
swelling of the submandibular gland after surgery in the

Ophthalmic injury All the complications that occur in the prone po-
sition are not because of the position but because of
Post operative visual loss (POVL) is relatively rare,
the failure to identify since the patient is unconscious
but the two injuries that are commonly described are
under general anesthesia and cannot tell the anesthe-
ischemic optic neuropathy and central retinal artery oc-
siologists of the signs and symptoms of that particular
clusion. Other complication which have been observed
complications. However this is not the case with re-
in the prone, anesthetised patient include supra orbital
gional anesthesia. Since the patient is conscious he
neuropraxia, transient and permanent ophthalmoplegia
will be in a position to alert the anesthesiologist of the
or cavernous sinus thrombosis. Central retinal vein oc-
impending complications that can take place and the
clusion, painful orbital compartment syndrome, bilateral
anesthesiologists take preventive measures; who is
close angle glaucoma, keratoconjunctival surgery and
otherwise unaware of the impending risk and there are
post operative chemosis. Opthalmic complications are
no monitoring devises for all the complications that can
recognised in patients who have been prone under
occur in a patient in prone position. So a conscious
GA and can be devastating. Hence preop counsel-
patient is himself / herself a reliable monitor to the
ing should be undertaken to understand POVL as a
anesthesiologist of the impending complication of the
potential risk.
prone position.
Embolic complications
In addition to this it is well documented that ac-
These could be venous gas embolism or non cidental extubation are common in the prone position
gaseous embolism. Venous gas embolism can occur and can be fatal if not recognized early. In addition to
because of increased negative pressure gradient be- this there are documented data which showed repeated
tween right atrium and veins at the operative site. Non tracheal tube obstruction as a result of secretions drain-
gaseous emboli like fat, cement or bone fragments are ing under gravity, and tube obstruction by inspissated
documented. secretion, which will not be seen if the techniques of
Regional anesthesia for prone position anesthesia is regional.
Regional anesthesia for prone position is being Management of cardiac arrest in prone position
increasingly used because of the various advantages Conventional teaching has been that on the oc-
this techniques has over GA. However these are currence of life threatening adverse event, the patient
certain concerns with RA namely : a) Ascent of block should be returned to supine position and this clearly
in prone position b) What if the RA fails and c) What has advantage in terms of access to the airway, pre-
happens in a critical event. cordium and familiarity. But this may not always be
However the various benefits of the RA are: possible especially when there is instrumentation of
the back. However chest compression are possible
1. Multiple indications
in the prone position and may generate higher systolic
2. Ease of performing RA BP and improves compression ventilation. In addition
patients can be defibrillated in the prone position with
3. Reduces the likelihood of joint injury / pressure
lateral pad position.
injury of upper limbs
Conclusion
4. Reduces the eye injuries
To conclude, there are several procedures which
5. Improved patient satisfaction
are done in the prone position like surgery on lower
6. Good post op analgesia back, PCNL, pilonidal sinus regions, tendo achilles
7. Reduced lower limb venous thrombosis and repair and many more. All these procedures can be
performed under regional anesthesia if there are no
8. Avoids a GA contraindications for RA as RA has several advantages

over GA, especially in the prone position which is asso- 7. Reverse CPR: a pilot study of CPR in the prone position
ciated with several avoidable complications. Since the Resuscitation. 2003 Jun;57(3):279-85
patient is conscious he will be in a position to alert the 8. Cardiopulmonary resuscitation in prone position: a
anesthesiologist about the impending catastrophe. In simplified method for outpatients. J Chin Med Assoc.
addition accidental extubation and tracheal tube blocks 2006 May;69(5):202-6.
are avoided, in RA which are very common with prone
position. Hence RA alone the technique of choices for 9. Successful defibrillation in the prone position BJA 2009
prone surgeries if there is no contraindication for RA Sep;21(6):408-13.
otherwise. 10. Greenberg R, Tymms A. Alert for perioperative visual
References loss: an unusual presentation of an orbital haeman-
gioma during spinal surgery. Anaesth Intensive Care
1. H.Edgcombe et al. Anesthesia in the prone position,
2003; 31: 679–82
British Journal of Anesthesia 100 (2): 165–83 (2008)
11. Halfon MJ, Bonardo P, Valiensi S, et al. Central retinal
2. Practice Advisory for perioperative visual loss associ-
artery occlusion and ophthalmoplegia following spinal
ated with spine surgery: a report by the American So-
surgery. Br J Ophthalmol 2004; 88: 1350–2
ciety of Anesthesiologists Task Force on perioperative
blindness. Anesthesiology 2006; 104: 1319–28 12. Goettler CE, Pryor JP, Reilly PM. Brachial plexopathy
after prone positioning. Crit Care 2002; 6: 540–2
3. Cheng MA, Sigurdson W, Tempelhoff R, Lauryssen C.
Visual loss after spine surgery: a survey. Neurosurgery 13. Jain V, Bithal PK, Rath GP. Pressure sore on malar
2000; 46: 625–30; discussion 30–1 prominences by horseshoe headrest in prone position.
Anaesth Intensive Care 2007; 35: 304–5
4. Alexianu D, Skolnick ET, Pinto AC, et al. Severe hy-
potension in the prone position in a child with neurofi- 14. Jeon YT, Park YO, won Hwang J, Lim YJ, Oh YS, Park
bromatosis, scoliosis and pectus excavatum presenting HP. Effect of head position on postoperative chemosis
for posterior spinal fusion. Anesth Analg 2004; 98: after prone spinal surgery. J Neurosurg Anesthesiol
334–5 2007; 19: 1–4
5. Brimacombe J, Keller C. An unusual case of airway 15. Jericho BG, Skaria GP. Contact dermatitis after the
rescue in the prone position with the ProSeal laryngeal use of the PronePositioner. Anesth Analg 2003; 97:
mask airway. Can J Anaesth 2005; 52: 884 1706–8
6. Brown J, Rogers J, Soar J. Cardiac arrest during 16. Loewenthal A, De Albuquerque AM, Lehmann-Meurice
surgery and ventilationin the prone position: a case C, Otteni JC. Efficacy of external cardiac massage in
report and systematic review. Resuscitation 2001; 50: a patient in the prone position. Ann Fr Anesth Reanim
233–8 1993; 12: 587–9

Prone Position Surgeries Can Be Done Under
Neuraxial Block Alone - Con 229 Maheshbabu B V
01 PRONE POSITION SURGERIES CAN BE DONE UNDER

NEURAXIAL BLOCK ALONE - CON
Associate Professor Maheshbabu B V

Rangaraya Medical College,
Kakinada
The prone or ventral decubitus position is used abdomen hangs free, the loss of functional residual
primarily for surgical access to the posterior fossa of capacity is less in the prone position than in either the
the skull, the posterior spine, the buttocks and perirectal supine or the lateral position.
area, and the lower extremities.
Relatively ↑FRC but no change in FEV1(3)
Effect of prone position on different systems (1)
• Upright and conscious - supine, anaesthetized,
Respiratory system and paralyzed: FRC ↓44%
Prone positioning has a broadly positive effect • Upright and conscious - prone, anaesthetized and
on the respiratory system provided that abdominal paralyzed FRC ↓12%
compression is avoided. Functional residual capacity
Visco- elastic properties of the chest wall - resis-
(FRC) and arterial oxygen tension both increase. This
tance ↑20% but is of no clinical significance. Reduction
is partly the reason why prone positioning has been
of cephalad pressure on the diaphragm and the reopen-
used in intensive care settings for patients with poor
ing of atelectatic segments - FRC ↑ (relatively).
lung function – often secondary to acute lung Injury.
It is most likely that changes in ventilation and perfu- Cardiovascular system
sion result in better V/Q matching, and thus improved The most important feature of turning a patient
arterial oxygen tension. Alveolar ventilation is more prone under anesthesia is a drop in cardiac output.
homogeneously distributed in the prone than in the Cardiac index in one study dropped by an average of
supine position (2). 24%. This is mainly as a result of decreasing stroke
If the thorax is supple or compliant, the body volume with little change in heart rate. Of the three fac-
weight of an anesthetised, prone patient compresses tors involved in cardiac output (preload, afterload and
the anterior posterior diameter of relaxed chest. If the contractility), it seems likely that decreased preload is
particular prone position in use allows the pressure of the most important factor, because of the compression
the abdominal viscera to be sufficient to force in dia- of the inferior vena cava (IVC) reducing venous return
phragm cephalad, the lung is shortened along its long to the heart. Increased intrathoracic pressure also
axis. When both the dorso-ventral and the cephalo- decreases the venous return.
caudal dimensions of the lung decreased, and in the When the IVC is itself obstructed, blood uses
presence of the relative vascular congestion of a zone a collateral return route – the vertebral wall venous
3 of west et al, the compliance of the compacted prone plexuses. As prone positioning is often used for spinal
lung can be anticipated to decrease. The result of de- surgery, this can cause increased bleeding in the surgi-
creased pulmonary compliance in a poorly positioned, cal field. Several Studies(4,5,6) assessed hemodynamic
prone, anesthetized patient is either an increased work response to prone position
of spontaneous ventilation or the need for higher infla-
• ↓ Stroke volume, ↓ Cardiac index
tion pressures during positive pressure ventilation.
• ↑SVR, ↑PVR
Proper positioning can retain more nearly normal
pulmonary compliance by minimizing the cephalad shift • HR, PAOP, Right atrial pressure: no change in the
of the diaphragm caused by compressed abdominal prone positioning during general anesthesia.
viscera. If the patient is properly arranged so that the

Complications associated with prone position(3) ciplinary approach for the control of pain or providing
balanced anesthesia and hence we cannot accept
Injuries to central nervous system
that neuraxial blockade alone is sufficient for prone
These injuries can be caused by different surgeries.
mechanisms—arterial occlusion, venous occlusion,
Risks or disadvantages of neuraxial blockade alone
air entrainment, cervical spine injury, or the effect of
for prone surgeries
undiagnosed space-occupying lesions.
1) Potential for high blocks and associated complica-
Injury to the peripheral nervous system
tions
Peripheral nerve injury may occur in patients
2) Limited access to air way
under anesthesia in any position and is thought to be
the end result of nerve ischemia from undue stretching 3) Uncomfortable position for long periods (very
or direct pressure. particularly in obese patients). If they are liberally
sedated, excessive dose of sedatives can pro-
Pressure Injuries
duce deep sedation and respiratory depression
These injuries can be thought of as being the leading to hypoxia. It is well documented that there
result of either direct pressure or indirect pressure will be variable response to benzodiazepines and
(when the injury occurs as a result of pressure on, or other sedative agents in different patients. Even
occlusion of, the vascular supply). small doses can produce excessive sedation and
Direct Injuries - Pressure necrosis of the skin, shoulder respiratory depression in some individuals. If
dislocation etc. this happens in prone patients, they may require
respiratory support and even repositioning. The
Indirect Injuries - macroglossia and oropharyngeal
prone position presents special risks for morbidly
swelling, visceral ischemia etc.
obese patients, whose respiration is already com-
Ophthalmic Injuries – Post operative visual loss(7) promised, and who may be difficult to reposition
quickly. High level neuraxial blockade and deep
The types of injury are
sedation will further worsen this condition. In fact,
1) Posterior ischemic optic neuropathy there is an increased incidence of failed blocks
(PION) in obese patients compared with similar, normal
2) Anterior ischemic optic neuropathy (AION) weight patients(8).
3) Central Retinal artery occlusion (CRAO) 4) May require repositioning during critical events
during the course of the surgery.
Distribution of injury – relative incidence - PION-60%;
AION-20%; CRAO-11% & undefined neuropathy-9%. 5) Inconvenient if neuraxial blockade fails or the
Only CRAO is associated with direct pressure on the duration is not sufficient for the completion of
globe. 90% of reported cases of POVL are not associ- surgery. If epidural is planned, the relaxation
ated with globe compression. Prolonged hypotension may not be sufficient enough for proper surgical
and reduced optic nerve perfusion pressure are con- exposure.
sidered as important etiologic factors for POVL. 6) For surgeries for posterior cranial fossa and other
Embolic Complications - Venous gas embolism, intra cranial lesions, general anesthesia is man-
Non-gaseous embolisms datory. Awake craniotomies are not feasible and
practicable for all the cases.
All these complications can be prevented to a
major extent by careful handling of the patient’s neck, 7) Surgical access is hindered when the patient
proper padding of the pressure points and taking care breaths spontaneously and increased muscle
of the eyes. This is an era of multi-model or poly-dis- tone (like in Georgia prone position) increases

bleeding and impair the surgical field even alone to tolerate tracheal compression under spontane-
more. ous breathing and they need tracheal intubation and
preferably controlled ventilation.
8) Neuraxial blockade has a limited effect on in-
flamed spinal nerve roots. Precautions to be taken during general anesthesia
to avoid the complications
9) When hypobaric solutions of local anesthetics are
used, the level of the blockade is unpredictable. 1) If reinforced endotracheal tubes are used and
properly secured, the problems of compression
10) The cardiovascular complications of prone posi-
and accidental extubation can be totally pre-
tion like decreased venous return (preload) lead-
vented.
ing to decreased cardiac output & CI are further
aggravated by neuraxial blockade. 2) If the doses of I.V induction agents like propofol
and thiopentone are properly titrated or co-induc-
11) In patients under neuraxial blockade in prone
tion is planned, there will not be any undesirable
position, work of breathing increases in spontane-
hemodynamic changes.As the cardiac output
ous ventilation and this depends on the level of
decreases in prone position, the doses of propofol
blockade.
and thiopentone may be reduced.
12) Prolonged surgeries in prone position under
3) Proper positioning of the neck like in neutral posi-
neuraxial blockade alone will produce lot of
tion will prevent the complications of traction of
stress and anxiety for both the surgeon and the the plexuses, cord compression etc.
anesthesiologist.
4) Proper padding and gentle handling of the patient,
13) Patients with polytrauma, very particularly with while turning to prone position can prevent pres-
facial injuries, air way must be protected and pa- sure problems and peripheral nerve injuries.
tient should be subjected to general anesthesia
only. 5) Proper application of pads and prevention of direct
pressure on the eye balls and limited usage of
14) Deliberate hypotension technique can be used crystalloid I.V fluids will prevent eye injuries and
to minimize blood loss during major surgeries in facial edema.
prone position under general anesthesia only.
Desirable degree of hypotension cannot be pro- Care must be taken to ensure that
duced in patients under neuraxial blockade, as • Abdomen is as free as possible.
this effect is further aggravated in them.
• Minimize direct chest compression or at least
Sadrolsadat SH, Mahdavi AR,Moharari RS et al (9) lower chest compression.
conducted a prospective trail comparing the technique
• Arms are kept either neutral at side or not > 90
of spinal and general anesthesia for lumbar disc
degrees abducted.
surgery and concluded that spinal anesthesia is not
preferable to general anesthesia. • Minimize dependent legs or use slight trendelen-
burg position.
Inci Kara, Jale Bengu Celik, Bahar OC et.al (10)
in their study - Comparison of spinal and general • Proper padding.
anesthesia in lumbar disc Surgery, concluded that By taking these precautions, the complications of
there was no significant difference as far as bleeding general anesthesia can be prevented and prone surger-
is concerned in between the patients operated under ies can be safely undertaken. In this modern anesthesia
the spinal anesthesia and general anesthesia. There practice, multi model approach is preferable, rather
were some reported cases of tracheal compression than following one technique only to render better pa-
in proneposition surgeries (11, 12). It will be very difficult tient care. Hence, the idea of neuraxial blockade alone
and unpleasant for a patient under neuraxial blockade for prone-position surgeries is not recommended.

References
1) H.Edgcombe.K.carter and S.Yarrow-Anesthesia in the 7) Lee et.al –Anesthesiology 2006 :105:652-9.
prone position-British Journal of Anesthesia100(2):165-
8) Regional anesthesia and obesity-Jerry Ingrande, Jay
83(2008)
B.Brodsky and Hendrikus J.M . Lemmens ; Current
2) Gattinoni L , Pelosi P,Valenza F,Mascheroni D:Patient opinion In Anesthesiology 2009,22:683-686
positioning in acute respiratory failure, Principles and
9) Sadrolsadat SH, Mahdavi AR, Moharari RS, Khajavi
practice of mechanical ventilation.Edited by Tobin
MR, Khashayar P, Najafi A, Amirjamshidi A
M.New York,Mc Graw Hill,2004.pp1067-76
A prospective randomized trial comparing the technique
3) Pelosi P and L. Gattinoni et al 1997-Respiratory Sys-
of spinal and general Anesthesia for Lumbar disc sur-
tem mechanics in sedated , paralysed, morbidly obese
gery , a study of 100 cases .Surg Neurol 2009;71:60-
patients,J.Appl.Physiol.83;811-818
65
4) Backofen JE, Schauble JF. Hemodynamic changes
10) Inci KARA, Jale Bengu CELIK et.al-Comparison of
with prone positioning during general anesthesia. An-
spinal and general anesthesia in lumbar disc surgery
esthesia Analgesia 1995; 64: 194
-2001,volume 28, number 4, pages 487-496
5) Wadsworth R. et al. The effect of four different surgi-
11) Mesrobian RB, Epps JL. Midtracheal obstruction after
cal prone positions on cardiovascular parameters in
Harrington rod placement in a patient with Marfan’s
healthy volunteers. Anesthesia. 1996 Sep;51(9):819-
syndrome.Anesth Analg 1986; 65: 411–3
22
12) Kai Y, Yamaoka A, Irita K, Zaitsu A, Takahashi S.
6) Sudheer PS et al.. Hemodynamic effects of the prone
Transient tracheal obstruction during surgical correc-
position: a comparison of propofol total intravenous
tion of scoliosis in apatient with Marfan’s syndrome.
and inhalation anesthesia. Anesthesia, 2006 Feb;61(2):
Masui 1995; 44: 868–73
138–141)

VIDEO SESSIONS


Basic Echocardiography in Clinical Anesthesia 235 Thomas Koshy
01 BASIC ECHOCARDIOGRAPHY IN CLINICAL ANESTHESIA
Professor, Cardiac Anesthesiology Thomas Koshy

Sree Chitra Tirunal Institute for Medical
Sciences and Technology
Trivandrum
Echocardiography – the use of ultrasound to ex- structures. From these reflections, distance, velocity
amine the heart is a safe, powerful, non-invasive and and density of objects within the chest are derived.
painless technique. The introduction of transesopha- Forming the image interaction of ultrasound waves
geal echocardiography (TEE) has provided a new with tissues
acoustic window to the heart and mediastinum. High-
The formation of an ultrasonic image is depen-
quality images of most cardiovascular structures can
dent upon wave reflections occurring at the interfaces
be obtained readily. TEE has revolutionized cardiac
between different media. The strength of reflection at
anesthesia and has become increasingly important
an interface depends upon the difference in acoustic
in the management of patients in the ICU and during impedance between the two media. For example, a
certain non-cardiac surgical procedures as well. As blood-fat interface produces a stronger reflection than
we view the field of echocardiography in the current a blood-muscle interface, because there is a greater
decade, it is almost impossible to conceive of a state- difference in density between blood and fat than be-
of-the-art cardiac OR without an echo machine. tween blood and muscle.
How echo helps in OR/ ICU When an ultrasound wave is propagated through
• Augment preoperative evaluation a living tissue, it is partly absorbed, partly reflected,
and partly scattered. Attenuation refers to the loss of
• Surgical decision planning ultrasound power as it transverses tissue. Ultrasound
• Evaluation of surgical results reflection, scattering and absorption are responsible
for tissue attenuation. A high percentage of ultrasound
• Hemodynamic assessment/ Differential diagnosis is absorbed by the tissues and is converted to heat,
of hypotension the higher the frequency the greater the absorption.
TEE is associated with a long learning curve The greater the ultrasound reflection and scattering,
because the complexities of transducer positioning, the less ultrasound energy is available for penetration
imaging sector alignment and the three dimensional and resolution of deeper structures. Water, blood and
cardiac anatomy, that are not familiar to most begin- muscle have low tissue impedance resulting in low ul-
ners. trasound attenuation, whereas air and bone have very
high tissue ultrasound impedance, limiting the ability
Physics of ultrasound of ultrasound to transverse these structures. Because
Basic principles sound waves travel through soft tissue at a constant
velocity, the length of time for the ultrasound beam
In TEE, the heart and great vessels are insonated to be returned back to the tranducer can be used to
with ultrasound from probe inside the esophagus, calculate the precise distance between the tranducer
which is sound above the human audible range (fre- and the object being interrogated.
quency above 20.000 Hz). Frequency within the range
Ultrasonic transducers
of human hearing (20-20,000 Hz) are referred to as
audio frequencies, while those above this range are A transducer is a device that converts energy
referred to as ultrasonic frequencies. Echocardiography from one form into another. Ultrasonic transducers
machines commonly operate in the frequency range use piezoelectric crystals to emit and receive high-
of 2-10 million cycles per second (2-10MHz). The frequency sound waves. These transducers convert
ultrasound is partially reflected by the cardiovascular electrical energy from the ultrasound instrument into

acoustic energy when transmitting, and they convert the gap between the aortic valves during diastole
acoustic energy reflected from the tissues into electri- within the cardiac cycle. Because M-mode images are
cal energy, that is used by the instrument to form the updated 1000 times per second, they provide greater
image. temporal resolution than 2D echo, thus, more subtle
A transducer with a mechanism to sweep the changes in motion or dimension can be appreciated.
ultrasound beam automatically in a fan-like fashion is The ultrasound signal should be aligned perpendicu-
called a mechanical sector scanner. In a phased array larly to the structure being examined. Finer analysis
scanner, the ultrasonic beam is formed and steered of valve motion or thickness and motion of cardiac
by firing an array of small closely spaced transducer chambers are best done in this view.
elements in a sequence. A TEE probe typically has 64 Two-dimensional echo (2D echo)
elements. (fig 1)
The acquired image which resembles an anatomic
section of the heart is easily interpreted (fig 3). This
2D echo image (“live” real image) is obtained by rapid,
repetitive scanning along many different radii within
an area in the shape of a fan (sector). Information
on structures and motion in the plane of a 2D scan is
updated 30 to 60 times per second.
Fig 1: A pediatric TEE probe inside the esophagus

in the OR
Imaging techniques
M MODE
This is the most basic form of ultrasound imaging.
In this mode, the density and position of all tissues in
the path of a narrow ultrasound beam (i.e., along a
single line) are displayed (fig 2). M-mode is not currently
used as a primary imaging mode because only a very
limited part of the heart is being observed. However
this mode is useful for the precise timing of events
Fig 3:2D TEE image of the left ventricle in diastole

and systole
Doppler ultrasound
Doppler echo uses the reflection of ultrasound by
Fig 3: A TEE M-mode image taken across the aortic moving red blood cells. The reflected ultrasound has a
root (box like structure) having regurgitation. Note frequency shift relative to the transmitted ultrasound,

determined by the velocity and direction of blood flow.

The Doppler effect is defined as the apparent change
in the frequency of waves occurring when the source
and observer are in motion relative to each other, with
frequency increasing when the source and observer
approach each other and decreasing when they move
apart. To obtain sufficient signal strength and pen-
etration for a good Doppler signal, higher ultrasonic
intensity levels and lower frequencies are used than
for 2-D imaging.
All modern echo machines combine Doppler capa-
bilities with 2D imaging facilities. After the desired view
Fig 4: Pulse wave Doppler of the mitral inflow
of the heart has been obtained by 2D echo, the Doppler
beam, represented by a cursor, is superimposed on the Continuous wave doppler
2D image. The operator positions the cursor as parallel Two crystals are used-one transmitting continu-
as possible to the assumed direction of blood flow. In ously and one receiving continuously. This technique
clinical practice, a deviation from parallel of up to 20 is useful for measuring high velocities but its ability to
degrees can be tolerated, because this only results in localize precisely a flow signal is limited since the signal
an error of 6% or less. can originate at any point along the length or width of
Doppler echo is used to measure the severity of the ultrasound beam.
valvular stenosis, quantify valvular regurgitation and it Color flow doppler
can also show intracardiac shunts. Doppler technol-
ogy is usually used in three different ways to measure Color flow doppler uses pulsed-wave technology
blood velocities: pulse wave, continuous wave and to measure blood flow velocity at multiple sites. Here
color flow. real time blood flow is displayed within the heart as
colors, while also showing 2D images in black and
Pulsed wave doppler white. The velocities and directions of blood flow are
This allows a flow disturbance to be localized or color encoded. Color flow doppler velocities away from
blood velocity from a small region to be measured (fig the transducer are in blue, those towards it in red.
4). A single crystal is used to transmit an ultrasound Transthoracic echo
signal and then to receive after a pre-set time delay.
There is a limit to the maximum velocity that can be Routine echocardiography examination begins
accurately detected, before a phenomenon known as with transthoracic two-dimensional (2D) scanning from
‘aliasing’ occurs usually at velocities in excess of 2 four standard transducer positions: the parasternal, api-
m/s cal, subcostal (subxiphoid), and suprasternal windows.
The parasternal and apical views usually are obtained
with the patient in the left lateral decubitus position and
the subcostal and suprasternal notch views, with the
patient in the supine position. From each transducer
position, multiple tomographic images of the heart rela-
tive to its long and short axes are obtained by manually
rotating
Transesophageal echo
Trans thoracic echocardiogram views are par-
ticularly difficult to obtain in patients with obesity,

emphysema, or abnormal chest wall anatomy because flexes the tip of the probe to the left or to the right (lateral
bone, fat and air containing lung interfere with ultrasonic flexion). This facility (lateral flexion) may not be avail-
penetration. To avoid these problems, TEE transduc- able in pediatric probe because of the size limitation.
ers were developed. They are mounted on modified All modern TEE probes are multiplane as compared
probe similar to those used for upper gastrointestinal to older biplane probes and the scanning plane can
endoscopy. Sound waves emitted from an esophageal be rotated from 00 to 1800. At 00 the sector scan lies
transducer only have to pass through the esophageal in the transverse image plane and runs perpendicular
wall and the pericardium to reach the heart, improving to the shaft of the probe. At 900 the sector scan lies in
image quality and increasing the number of echocardio- the longitudinal or vertical plane and runs parallel to
graphic windows. Other advantages of TEE include the the shaft of the probe.
stability of the transducer position and the possibility of
A transducer icon which indicates the degrees
obtaining continuous recordings of cardiac activity for
of imaging sector rotation is located at the upper right
extended periods of time (for e.g. during cardiac sur-
hand corner of the image display. It allows tracking
gery). Majority to TEE probes uses ultrasound between
the degrees of forward or backward multiplane angle
3.5 and 7 MHz. Two types of probes are available in
rotation.
the market. The adult probe has a shaft length of 100
cm and a diameter of around 12 mm. This can be Preparation for TEE examination
introduced in patients up to 20-25 Kgm. The pediatric Anesthesiologists may need to insert the TEE
probe measures approximately 7 mm in diameter and probe in awake or anesthetized patients. In both
the company recommends its use in patients weighing scenarios, the probe needs to be well lubricated.
upto 4 Kgm. One needs to be very careful in patients with history
Movements of the TEE probe of dysphagia, hemetemesis, operations on GIT and
cervical spine disease. Introduction of TEE probe into
The TEE probe produces a 900 imaging sector
the esophagus in intubated patients under general
which can be directed by a variety of maneuvers (fig
anesthesia may be difficult at times and alternative
5). The shaft of the probe may be advanced into or
maneuvers are described in literature. An awake patient
withdrawn from the esophagus and turned to the right
must be fasting for at least 4-6 hours before the pro-
(clockwise) or to the left (anticlockwise). The tip of the
cedure. Blood pressure and heart rate are measured.
probe may be anteflexed (anteriorly) or retroflexed
Dentures and oral prostheses should be removed.
(posteriorly) by rotating the large control wheel on the
Airway, oxygen delivery system, bite guard, suction,
handle of the probe. Rotating the small control wheel
standard crash cart should be immediately available.
An intravenous access is generally established before
TEE examination.
Premedication
Awake patients are usually premedicated for the fol-
lowing reasons:
• Topical anesthesia: of oropharynx and hard and
soft palates diminishes gag reflex. It can be pro-
duced by an aerosol local anesthetic like lidocaine
solution or viscous lidocaine.
• Sedation: is carried out intravenously to decrease
anxiety and discomfort, with administration of a
sedative belonging to the benzodiazepines group
Fig 5: Movements of the TEE probe (e.g. diazepam or midazolam).

• Drying agents: lessen salivary and gastrointesti- The apex of the sector scan is shown at the top
nal secretions reducing the risk of aspiration (e.g. of the echo screen, which displays posterior cardiac
glycopyrrolate) structures (parts closer to the probe in the esophagus).
In the transverse imaging plane (transducer at 00), the
• Antibiotics: help prevent infective endocardi-
left of the image is towards patient’s right, and the right
tis in selected high-risk patients. The issue of
of the image is towards the patient’s left. In the vertical
endocarditis prophylaxis during TEE remains
image plane (900), the left side of the image is inferior
controversial. Since the procedure is similar to
and points towards the patient’s feet and right side of
that of endoscopic examinations, there may be
the image is anterior and points towards the patient’s
some merit to administering bacterial endocarditis
head.
prophylaxis.
Centering the image
Technique of introduction
Once we centre a cardiac structure in one image
The pharynx is anesthetized with a topical an-
plane, it will continue to remain there as the trans-
esthetic spray. The patient is placed in the left lateral
ducer is rotated from 00 to 1800 facilitating the three-
position and the neck slightly flexed to allow better
dimensional assessment of that particular structure.
oropharyngeal entry. Introduction of the probe can also
To centre a structure in the transverse imaging plane
be performed with the patient in the supine position and
(00 rotation), the shaft of the probe should be turned
if necessary in the upright sitting position. A bite guard
to the left or to the right so that the structure of interest
is essential to allow manipulation and protection of the
is aligned in the middle of the display. If the probe is
TEE probe. Distal portion of the transducer is coated
in the vertical image plane (900 rotation) advancing or
with lubricating jelly. The echographer passes the probe
withdrawing the probe will achieve the same result.
tip through the bite guard and over the tongue maintain-
ing it in the midline. The tip is advanced until resistance Standard views and systematic examination
is encountered, then the patient is asked to swallow
Patient details are usually entered and the ma-
and with gentle forward pressure the transducer is
chine controls are adjusted for optimal resolution before
advanced into position behind the heart. When TEE
starting the examination. Images are collected at four
procedure is over, the precautions that should be taken
depths:
by the patient include not to drink any hot liquid until
oropharyngeal anesthesia has worn off (1-2 hours), • Upper esophageal
not to eat until gag reflex returns (1-4 hours) and not • Mid esophageal
to drive for 12 hours (if a sedative was given).
• Transgastric
Standard image display
• Deep transgastric
It is imperative that an examiner be comfortable
The American Society of Echocardiography and
with imaging sector orientation and the resulting image
the Society of Cardiovascular Anesthesiologists had
display. These are key concepts. Mastering them will
published guidelines for comprehensive intraopera-
allow to predict the images which will result from the
tive multiplane TEE examination. They recommend
various probe manipulations and to display a desired
20 standard images. They are shown below (fig 6).
cross-section.

Fig 6: Standard images for a systematic TEE examination
Various views and images will be presented in the depth, and then the probe is manipulated to orient the
conference. The great majority of images are obtained imaging plane to obtain the desired cross-sectional im-
at mid esophageal and transgastric levels. The goal is age. This is achieved by watching the image develop
not to get all 20 views in all patients. The goal is to elu- as the probe is manipulated, rather than by relying on
cidate the structure and function of the heart and great the depth markers on the probe or the multiplane angle
vessels. The transducer is first moved into the desired icon.

Mid esophageal views

The mid-esophageal (ME) views fall into two
groups: ME aortic views and ME ventricular views.
Mid-esophageal aortic views
These views image the aortic valve and proximal
ascending aorta. Six views are obtained at this level:
ME aortic valve short axis (SAX), ME aortic valve long
axis (LAX), ME right ventricle inflow-outflow view, ME
bicaval view, ME ascending aorta SAX and ME as-
cending aorta LAX. The aortic root, aortic valve cusps,
inter atrial septum, right ventricle, tricuspid valve, and
the vena cavae are assessed with these views. (fig
7)
Fig 7: Important mid esophageal aortic views
Mid-esophageal ventricular views
Fig 8: Commonly used mid esophageal ventricular views
These views (four-chamber, two-chamber, com- is further advanced into the stomach and anteflexed
missural, and LAX) are important in the assessment of (to keep it apposed to the diaphragmatic surface of the
mitral valve, left ventricle, inter ventricular septum and stomach) to develop the transgastric (TG) views (fig
both atrium (fig 8). Progressive rotation of the trans- 9). The five views (TG mid SAX, TG two chamber, TG
ducer from the four-chamber view (00) to long-axis view basal SAX, TG LAX, TG RV inflow) obtained at this level
(1300) allows visualization of all segments of anterior are useful in the assessment of the mitral valve and left
and posterior mitral leaflets and a complete evaluation and right ventricles. In particular the transgastric mid
of left ventricular wall motion. SAX view is very commonly used by the anesthesiolo-
Transgastric views gists in the assessment of LV function, ejection fraction
and volume status.
From the mid-esophageal position the TEE probe

Fig. 9: Transgastric and deep transgastric views
To obtain deep TG LAX view, the probe is

advanced further into the stomach and then slowly
withdrawn with tip sharply anteflexed until it contacts
the diaphragmatic surface of stomach wall. This view
shows all four cardiac chambers, aortic valve and the
left ventricular outflow tract. Since the ultrasound beam
is parallel to the blood flow through the aortic valve, this
image is ideal for estimation of velocity through the AV
and cardiac output.
Descending thoracic aorta, aortic arch views
TEE can image both aortic arch and descending
aorta with four standard views (Upper esophageal
aortic arch SAX & LAX, Descending aortic SAX & LAX)
(fig 10).
Fig 10: Long axis and short axis views of aortic

arch and descending aorta

Indications • Intraoperative use for endocarditis when preop-

erative testing was inadequate or extension of
Intraoperative TEE imaging enabled anesthesiolo-
infection to perivalvular tissue is suspected
gists and surgeons to diagnose myocardial ischemia
confirm the adequacy of valve reconstruction and other • Preoperative use in unstable patients with sus-
surgical repairs, determine the cause of hemodynamic pected thoracic aortic aneurysms, dissection, or
disorders and other intraoperative complications, and disruption who need to be evaluated quickly
provide diagnostic information that could not be ob-
• Intraoperative assessment of aortic valve function
tained preoperatively. Real-time access to this informa-
in repair of aortic dissections with possible aortic
tion has enabled surgeons to correct inadequate repairs
valve involvement
before patients leave the operating room, has reduced
the need for reoperation, and has facilitated the preven- • Intraoperative evaluation of pericardial window
tion and early treatment of perioperative complications. procedures
Anesthesiologists use TEE increasingly to evaluate
• Use in intensive care unit for unstable patients
and treat unstable patients in OR as well as ICU, as
with unexplained hemodynamic disturbances,
it provides important hemodynamic parameters. TEE
suspected valve disease, or thromboembolic
examination is generally safe, but manipulation of the
problems (if other tests or monitoring techniques
probe can compress important neighbouring structures
have not confirmed the diagnosis or patients are
or produce injuries.
too unstable to undergo other tests)
Recommendations for performing TEE are
Category II indications
intended for those anesthesiologists who use TEE,
rather than for all anesthesiologists. The recommen- • Perioperative use in patients with increased risk
dations are divided into three categories based on the of myocardial ischemia or infarction
strength of supporting evidence or expert opinion that
• Perioperative use in patients with increased risk
the technology improves clinical outcomes. Category I
of hemodynamic disturbances
indications are supported by the strongest evidence
or expert opinion; TEE frequently is useful in improv- • Intraoperative assessment of valve replacement
ing clinical outcomes in these settings and often is
• Intraoperative assessment of repair of cardiac
indicated. Category II indications are supported by
aneurysms
weaker evidence and expert consensus; TEE may be
useful in improving clinical outcomes in these settings. • Intraoperative evaluation of removal of cardiac
Category III indications have little current scientific or tumors
expert support; TEE infrequently is useful in improving • Intraoperative detection of foreign bodies
clinical outcomes in these settings, and appropriate
indications are uncertain. • Intraoperative detection of air emboli during car-
diotomy, heart transplant operations, and upright
Category I indications neurosurgical procedures
• Intraoperative evaluation of acute, persistent, and
• Intraoperative use during intracardiac thrombec-
life-threatening hemodynamic disturbances in
tomy
which ventricular function and its determinants are
uncertain and have not responded to treatment • Intraoperative use during pulmonary embolec-
tomy
• Intraoperative use in valve repair
• Intraoperative use for suspected cardiac trauma
• Intraoperative use in congenital heart surgery for
most lesions requiring cardiopulmonary bypass • Preoperative assessment of patients with suspect-
ed acute thoracic aortic dissections, aneurysms,
• Intraoperative use in repair of hypertrophic ob-
or disruption
structive cardiomyopathy

• Intraoperative use during repair of thoracic aor- • Left atrial pressure

tic dissections without suspected aortic valve
• Left ventricular end diastolic pressure
involvement
• Cardiac output
• Intraoperative detection of aortic atheromatous
disease or other sources of aortic emboli • Stenotic valve orifice areas
• Intraoperative evaluation of pericardiectomy, • Regurgitant valve orifice areas

pericardial effusions or evaluation of pericardial Complications
surgery
Complications resulting from TEE can be separated
• Intraoperative evaluation of anastomotic sites into two groups:
during heart and/or lung transplantation
1. Injury from direct trauma to the airway and
• Monitoring placement and function of assist de- esophagus
vices
• Esophageal bleeding, burning, tearing
Category III indications
• Dysphagia
• Intraoperative evaluation of myocardial perfusion,
• Laryngeal discomfort
coronary artery anatomy, or graft patency
• Bacteremia
• Intraoperative use during repair of cardiomyopa-
thies other than hypertrophic obstructive cardio- • Vocal cord paralysis
myopathy 2. Indirect effects of TEE
• Intraoperative use for uncomplicated endocarditis • Hemodynamic and pulmonary effects of
during noncardiac surgery airway manipulation
• Intraoperative monitoring for emboli during ortho- • Distraction from patient
pedic procedures
Contraindications
• Intraoperative assessment of repair of thoracic
Absolute contraindications to TEE in intubated pa-
aortic injuries
tients include esophageal stricture, diverticula, tumor,
• Intraoperative use for uncomplicated pericardi- recent suture lines and known esophageal interruption.
tis Relative contraindications include symptomatic hiatal
• Intraoperative evaluation of pleuropulmonary hernia, esophagitis, coagulopathy, esophageal varices,
diseases and unexplained upper gastrointestinal bleeding.
• Monitoring placement of intraaortic balloon Safety guidelines

pumps, automatic implantable cardiac defibrilla- To ensure continued safety of TEE, the follow-
tors, or pulmonary artery catheters ing points may be noted. The TEE probe should be
inspected prior to each insertion for cleanliness and
• Intraoperative monitoring of cardioplegia admin-
structural integrity. It should be inserted gently and if
istration
resistance is met, the procedure should be aborted.
Hemodynamic parameters The image is frozen when not in use and the probe
TEE allows the anesthesiologist to obtain multiple should be left in the neutral, unlocked position to pre-
hemodynamic parameters to guide in the care of the vent prolonged pressure on the esophageal mucosa.
patient. Some of them are listed below. Conclusion
• Right ventricular systolic pressure TEE has become the cornerstone in the non-
• Pulmonary artery diastolic pressure invasive diagnostic evaluation and monitoring of

patients with suspected cardiovascular diseases or 6. Practice guidelines for perioperative TEE: Anesthesiol-
hemodynamic instability. Further TEE is an image ogy 1996:84:986-1006
based technology and is best learned through printed 7. Koshy T, Vijayakumar A, Sinha PK. Unrecognized de-
materials, video loops and regular hands-on training. scending thoracic aortic compression by transesopha-
References geal echocardiographic probe in an infant undergoing
cardiac surgery – Its recognition and prevention. J or
1. Sidebotham D, Merry A, Legget M (eds):Practical
Cardiothorac Vasc Anesth 2006;21:727-729.
perioperative transoesophageal echocardiography,
Philadelphia, Butterworth Heinemann, 2003 8. Sinha PK, Koshy T: Reverse Sellick’s Maneuver for
Transesophageal Echocardiographic Probe Place-
2. Khan RA, Sherna SK, Konstadt SN: Intraoperative
ment- J Cardiothorac Vasc Anesth 2007;21:626-628.
Echocardiography in Kaplan JA (ed): Kaplan’s cardiac
Anesthesia, Philadelphia, Saunders Elsevier, 2006, pp 9. Koshy T, Kumar B, Sinha PK: Transesophageal
437-488 echocardiography and Anesthesiologist. Indian Journal
of Anesthesia 2007;51:324-333
3. Shanewise JS, Cheung AT, Aronson S et al: ASE/SCA
guidelines for performing a comprehensive intraopera- 10. Side CD, Gosling RG. Non-surgical assessment of
tive multiplane TEE examination. Anesthesia Analgesia cardiac function. Nature 1971; 232: 335-6.
1999;89:870884
11. DiMagno EP, Buxton JL, Regan PT et al. Ultrasonic
4. Kaddoura S (ed): Echo made easy, Philadelphia, endoscope. Lancet 1980; 1: 629-31.
Churchill Livingstone, 2002
12. Souquet J, Hanrath P, Zitelli L, et al. Transesophageal
5. Szokol JW, Murphy GS: Transesophageal echocar- phased array for imaging the heart. IEEE Trans Biomed
diographic monitoring of hemodynamics in Vender JS, Eng 1982; 29: 707-12.
Szokol JW, Murphy G (eds): International Anesthesiol-
13. Kneeshaw JD. Transesophageal echocardiography in
ogy Clinics, Philadelphia, Lippincott Williams & Wilkins,
the operatng room. Br J Anaesth 2006; 97: 77-84.
2004, pp 59-81

BREAKFAST SESSIONS


Acid Base Physiology 248 Lakshmi Kumar
01 ACID BASE PHYSIOLOGY
Amrita Institute of Medical Sciences, Lakshmi Kumar

Kochi
The body maintains a homeostasis between the excreted by the kidney. The above total for net fixed
acid produced and excreted to maintain a pH between acid production excludes the lactate produced by the
7.36 -7.44. A number of regulatory mechanisms exist body each day as the majority of the lactate produced
that keep the balance. is metabolized and is not excreted so there is no net
lactate requiring excretion from the body.For acid-base
The pH of the body is kept in control by 3 systems.
balance, the amount of acid excreted per day must
1. The chemical acid - base buffering system that equal the amount produced per day. The routes of
combines with the body fluids and will immediately excretion are the lungs (for CO2) and the kidneys (for
keep the pH under control. the fixed acids). Each molecule of CO2 excreted via
2. The respiratory center that regulates the removal the lungs results from the reaction of one molecule of
of volatile carbon-dioxide as a gas in the expired bicarbonate with one molecule of H+. The H+ remains
air from the plasma and regulates bicarbonate in the body as H2O.
from the body fluids through the pulmonary cir- Buffer systems in the body
culation. This response occurs within minutes.
A buffer is a solution containing substances that
3. The kidneys that adjust the acidity and alkalinity has the ability to minimize changes in pH when an acid
of the urine and thereby regulate the pH of the or base is added to it.
blood. This response can take as long as several
The major buffer system in the ECF is the CO2-
hours or days but is a more powerful regulatory
bicarbonate buffer system. This is responsible for about
system.
80% of extracellular buffering. It is the most important
The metabolic balance in the body is a balance ECF buffer for metabolic acids but it cannot buffer
between acids and bases. The acids are classified respiratory acid-base disorders.The components are
as volatile acids (carbon- dioxide as bicarbonic acid) easily measured and are related to each other by the
and fixed acids. Carbon dioxide is the end-product of Henderson-Hasselbalch equation.
complete oxidation of carbohydrates and fatty acids.
pH = pKa + log10 ( [HCO3] / 0.03 x pCO2)
It is called a volatile acid meaning in this context it can
be excreted via the lungs. The pKa value is dependent on the temperature,
[H ] and the ionic concentration of the solution. It has a
+
The fixed acids are usually referred to by their
value of 6.099 at a temperature of 370C and a plasma
anion (lactate, phosphate, sulphate, acetoacetate or
pH of 7.4. At a temperature of 300C and pH of 7.0, it has
beta-hydroxybutyrate). Fixed acids are produced due
a value of 6.148. For practical purposes, a value of 6.1
to incomplete metabolism of carbohydrates ( lactate),
is generally assumed and corrections for temperature,
fats (ketones) and protein ( sulphate, phosphate). Net
pH of plasma and ionic strength are not used except
production of fixed acids is about 1 to 1.5 mmoles of
in precise experimental work.
H+ per kilogram per day: about 70 to 100 mmoles of
H+ per day in an adult. This non-volatile acid load is pH = 6.1 + log ( [HCO3] / 0.03 pCO2 ).

The bicarbonate buffer system is an effective buffer system despite having a low pKa because the
body also controls pCO2
Site Buffer System Comment
ISF Bicarbonate For metabolic acids
Phosphate Not important
Protein Not Important
Blood Bicarbonate For metabolic acids
Hemoglobin Important for carbon dioxide
Protein Minor buffer
Phosphate Concentration low
ICF Proteins Important buffer
Phosphate Important Buffer
Urine Phosphate For titratable acidity
Ammonia For ammonium ion
Bone Calcium carbonate Metabolic acidosis
The other buffer systems in the blood are the They are accessible and easy to determine. Blood
protein and phosphate buffer systems. These are the gas machines measure pH and pCO2 directly and
only blood buffer systems capable of buffering respira- the [HCO3] is then calculated using the Henderson-
tory acid-base disturbances as the bicarbonate system Hasselbalch equation.
is ineffective in buffering changes in H+ produced by Bone also acts as a buffer as the carbonate and
itself. The phosphate buffer system is not an important phosphate salts present in the bone particularly in
blood buffer as its concentration is too low. The con- prolonged metabolic acidosis. Bone matrix contains
centration of phosphate in the blood is so low that it is hydroxyapatite crystals that account for nearly 65%
quantitatively unimportant. Phosphates are important of the bone volume. Bone contains carbon dioxide as
buffers intracellularly and in urine where their concen- bicarbonate and this can be substituted for phosphate
tration is higher. Hemoglobin is an important blood and hydroxyl in the apatite crystals. The mechanism
buffer particularly for buffering CO2. Protein buffers by which bone acts as a buffer is by ionic exchange or
in blood include hemoglobin (15mg/dl) and plasma by dissolution of bone crystal.
proteins (70g/l). Buffering is by the imidazole group of
the histidine residues which has a pKa of about 6.8. Respiratory regulation
This is suitable for effective buffering at physiological The respiratory regulation refers to the alterations
pH. Hemoglobin is quantitatively about 6 times more in the pH secondary to the changes in ventilation.
important then the plasma proteins as it is present Carbon-Dioxide is lipid soluble and crosses the cell
in about twice the concentration and contains about membranes rapidly and changes in ventilation will very
three times the number of histidine residues per mol- rapidly effect changes in pH.
ecule. Deoxyhemoglobin is a more effective buffer
The two key equations that establish this relation-
than oxyhemoglobin and this change in buffer capacity
ship are
contributes about 30% of the Haldane effect. The major
factor accounting for the Haldane effect in CO2 trans- 1. Alveolar ventilation – Arterial pCO2 relationship.
port is the much greater ability of deoxyhemoglobin to Changes in alveolar ventilation are inversely re-
form carbamino compounds. lated to the changes in arterial carbon dioxide.
The buffer systems which participate in defence of PaCO2 ∞ VCO2/ VA

acid-base changes are in equilibrium with each other.
Alternatively, PaCO2 = 0.863 x (V CO2/VA)
There is after all only one value for [H+] at any moment.
This is known as the isohydric principle. 2. Henderson- Hasselbalch equation
pH = pKa + log { [HCO3] / (0.03 x pCO2) }
Conventionally, the components of the bicarbon-
ate system ([HCO3] and pCO2) alone are measured. or

Henderson equation:[H+] = 24 x (pCO2 / HCO3). ton pump). Filtered HCO3- cannot cross the apical
The lungs are responsible for the excretion of carbon membrane of the PCT cell. Instead it combines with
dioxide and nearly 12,000 to 13,000 mmol/day is ex- the secreted H+ to produce CO2 and H2O. The CO2 is
creted. lipid soluble and easily crosses into the cytoplasm of
the PCT cell. In the cell, it combines with OH- to pro-
Kidney regulation
duce bicarbonate. The HCO3-crosses the basolateral
The kidneys in contrast are responsible for the membrane via a Na+-HCO3- symporter. This symporter
excretion of fixed acid which although account for a is electrogenic as it transfers three HCO3- for every
smaller amount of 70 -100 mmol/l is still crucial as there one Na+. In comparison, the Na+-H+ antiporter in the
are no alternative. The other major role by the kidneys apical membrane is not electrogenic because an equal
is the reabsorption of the filtered bicarbonate of about amount of charge is transferred in both directions.
4000-5000 mmol/day.
The functions of the proximal tubule is bicarbon- The basolateral membrane also has an active
ate reabsorption and ammonium ion production. Daily Na+-K+ ATPase (sodium pump) which transports 3
filtered bicarbonate equals the product of the daily Na+ out per 2 K+ in. This pump is electrogenic in a
glomerular filtration rate (180 l/day) and the plasma direction opposite to that of the Na+-HCO3- symporter.
bicarbonate concentration (24 mmol /l). Also the sodium pump keeps intracellular Na+ low which
sets up the Na+ concentration gradient required for the
This is 180 x 24 = 4320 mmols/day (4000 to 5000
H+-Na+ antiport at the apical membrane.The H+-Na+ an-
mmols/day).
tiport is an example of secondary active transport.
About 85 to 90% of the filtered bicarbonate is The net effect is the reabsorption of one molecule of
reabsorbed in the proximal tubule and the rest is reab- HCO3- and one molecule of Na+ from the tubular lumen
sorbed by the intercalated cells of the distal tubule and into the blood stream for each molecule of H+ secreted.
collecting ducts. The reactions that occur are outlined This mechanism does not lead to the net excretion of
in the diagram. Effectively, H+ and HCO3- are formed any H+ from the body as the H+ is consumed in the
from CO2 and H2O in a reaction catalysed by carbonic reaction with the filtered bicarbonate in the tubular lu-
anhydrase. The H+ leaves the proximal tubule cell men. The four major factors which control bicarbonate
and enters the PCT lumen by 2 mechanisms, Na-H reabsorption are luminal bicarbonate concentration,
antiporter (major route) and also by H+ - ATPase (pro- luminal flow rate, arterial pCO2 and angiotensin II.

An increase in any of these four factors causes The pKa for ammonium is so high (about 9.2) that
an increase in bicarbonate reabsorption. Parathyroid both at extracellular and at intracellular pH, it is present
hormone also has an effect: an increase in hormone entirely in the acid form NH4+. Most of the ammonium
level increases cAMP and decreases bicarbonate is involved in cycling within the medulla. About 75% of
reabsorption. the proximally produced ammonium is removed from
the tubular fluid in the medulla so that the amount of
Ammonium (NH4) is produced predominantly
ammonium entering the distal tubule is small. The thick
within the proximal tubular cells. The major source is
ascending limb of the loop of Henle is the important
from glutamine which enters the cell from the peritubu-
segment for removing ammonium. The ammonium
lar capillaries (80%) and the filtrate (20%). Ammonium
level in the DCT fluid is low because of removal in the
is produced from glutamine by the action of the enzyme
loop of Henle and the ammonium levels in the med-
glutaminase. Further ammonium is produced when the
ullary interstitium are high (and are kept high by the
glutamate is metabolised to produce alpha-ketoglu-
recycling process via the thick ascending limb and the
tarate. This molecule contains 2 negatively-charged
late PCT).
carboxylate groups so further metabolism of it in the
cell results in the production of 2 HCO3- anions. Distal tubular mechanism
This is a low capacity, high gradient system which
accounts for the excretion of the daily fixed acid load
of 70 mmols/day. The processes involved are:
1. Formation of titratable acidity (TA)
2. Addition of ammonium (NH4+) to luminal fluid
3. Reabsorption of remaining Bicarbonate
Regulation of renal H+ excretion
The major factors which regulate renal bicarbonate
reabsorption and acid excretion are:
1. Extracellular volume
Volume depletion is associated with Na+ retention
and this also enhances HCO3 reabsorption. Converse-
ly, ECF volume expansion results in renal Na+ excretion
and secondary decrease in HCO3 reabsorption.
2. Arterial pCO2
An increase in arterial pCO2 results in increased
renal H+ secretion and increased bicarbonate reabsorp-
tion. The converse also applies. Hypercapnia results in
an intracellular acidosis and this results in enhanced
H+ secretion. This renal bicarbonate retention is the re-
nal compensation for a chronic respiratory acidosis.
3. Potassium & Chloride deficiency
Potassium has a role in bicarbonate reabsorp-
tion. Low intracellular K+ levels result in increased
HCO3 reabsorption in the kidney. Chloride deficiency

is extremely important in the maintenance of a meta- no fixed acids. The CO2 diffuses out of the liver and
bolic alkalosis because it prevents excretion of the reactions in red cells result in production of H+ and
excess HCO3 ( the bicarbonate instead of chloride is HCO3-.
reabsorbed with Na+ to maintain electro neutrality).
The metabolism of various organic anions in the
4. Aldosterone & cortisol (hydrocortisone) liver results in consumption of H+ and regeneration of
the extracellular bicarbonate buffer.
Aldosterone at normal levels has no role in renal
regulation of acid-base balance. Aldosterone depletion These anions may be:
or excess does have indirect effects. High aldoster-
1. Exogenous ( citrate in blood transfusion, acetate
one levels result in increased Na+ reabsorption and
and gluconate from plasmalyte 148 solution, lac-
increased urinary excretion of H+ and K+ resulting in a
tate from Hartmann’s solution)
metabolic alkalosis.
2. Endogenous ( lactate from active glycolysis or
5. Phosphate excretion
anaerobic metabolism, keto-acids produced in
Phosphate is the major component of titratable the liver)
acidity. The amount of phosphate present in the distal
If the endogenous production of these anions is
tubule does not vary greatly. Consequently, changes in
followed by later consumption in the liver then there is
phosphate excretion do not have a significant regula-
no net production of acid or base because the H+ pro-
tory role in response to an acid load.
duced (from the dissociation of the acid) is consumed
6. Reduction in GFR when the anion is subsequently metabolized by the
liver.
It has recently been established that a reduction
in GFR is a very important mechanism responsible for When these organic anions are exogenously ad-
the maintenance of a metabolic alkalosis. The filtered ministered (eg in intravenous fluids), administration of
load of bicarbonate is reduced proportionately with a the anion (the conjugate base) without any H+ occurs
reduction in GFR. because the cation involved is Na+. Any subsequent
metabolism of these anions in the liver will consume
7. Ammonium
H+ and result in excess bicarbonate production. As an
The kidney responds to an acid load by increasing example, a metabolic alkalosis can result after a mas-
tubular production and urinary excretion of NH4+. The sive blood transfusion when the citrate anticoagulant
mechanism involves an acidosis-stimulated enhance- is metabolized to bicarbonate. The important point to
ment of glutamine utilization by the kidney resulting in note is how some of these anions (eg lactate, acetate)
increased production of NH4+ and HCO3- by the tubule are used in IV crystalloid solutions as a bicarbonate
cells. This is very important in increasing renal acid source (though this is indirect of course as the bicar-
excretion during a chronic metabolic acidosis. bonate is only produced when they are metabolized in
Role of the liver in acid base metabolism the body).
1. Carbon dioxide production from complete oxida- The key point to remember is that lactic acid is
tion of substrates. an acid but lactate is a base. The administration of
lactate in Hartmann’s solution can never result in a
2. Metabolism of organic acid anions (such as lac-
lactic acidosis because it is a base and not an acid.
tate, ketones and amino acids)
The solution contains sodium lactate and not lactic acid.
3. Metabolism of ammonium. The lactate anion is the conjugate base of lactic acid
and represents potential bicarbonate and not potential
4. Production of plasma proteins (mainly albumin).
H +.
Complete oxidation of carbohydrates and fat
which occurs in the liver produces carbon dioxide but

Endogenous lactate Ketones

Some excess lactate is normally produced in Keto-acids such as acetoacetate are produced
certain tissues and ‘spill over’ into the circulation. This in hepatic mitochondria due to incomplete oxidation
lactate can be taken up and metabolized in various of fatty acids. The ketones are released into the blood
tissues (myocardium) to provide energy. Only in the stream and metabolized in the tissues muscle). Hepatic
liver and the kidney the lactate can be converted back production of ketoacids produces H+ and the oxida-
to glucose (gluconeogenesis) as an alternative me- tion of the keto-anion in the tissues consumes H+ and
tabolism to carbon dioxide. The glucose may re-enter thereby regenerates the HCO-3 which had buffered it
the blood and be taken up by cells (muscle cells). This in the blood stream.
glucose-lactate-glucose cycling between the tissues is
The liver is the major producer of plasma proteins
known as the Cori cycle. Typically there is no net lactate
as nearly all except the immunoglobulins are produced
production which is excreted from the body. The renal
here. Albumin synthesis accounts for 50% of all hepatic
threshold for lactate is relatively high and normally all
protein synthesis and has the following functions:
the filtered lactate is reabsorbed in the tubules.
1. It is the major unmeasured anion in the plasma
The total amount of lactate involved is large
which contributes to the normal value of the anion
(1,500 mmols/day) in comparison to the net fixed acid
gap
production (1 to 1.5 mmols/kg/day). The metabolism
of lactate in the liver indirectly eliminates the H+ pro- 2. Extracellular buffer for CO2 and fixed acids
duced subsequent to the tissue production of lactate. 3. Abnormal levels can cause a metabolic acid-base
Lactic acidosis will result if this hepatic metabolism is disorder.
not adequate.
The above described mechanisms are the body’s
Metabolism of lactate sourced from IV Hartmann’s responses to maintain equilibrium in acid base balanc-
solution also results in a net consumption of H+, but as es. The changes occur with disorders of the respiratory
this lactate was associated with Na+, the overall result and the metabolic state and compensations occur to
is a net bicarbonate production. Effectively, metabolism keep the pH within the normal range.
of this lactate results in generation of an equivalent
References:
amount of bicarbonate. The situation is similar with
metabolism of citrate and gluconate in other IV fluids. 1. Oh’s Intensive Care Manual. Fifth Edition. Butterworth
Heinemann pg 873-884
2. Acid base Book.www.anesthesiamcq.com

Ultrasound in Anesthesia Practice – Its Role
in Nerve Blocks 254 TVS Gopal
01 ULTRASOUND IN ANESTHESIA PRACTICE – ITS ROLE

IN NERVE BLOCKS
Consultant Anesthesiologist TVS Gopal

Axon Anesthesia Associates
Hyderabad
Introduction (American Society of Regional Anesthesia) and the

ESRA (European Society of Regional Anesthesia),
NM Denny and William Harrop-Griffiths, in an
has dedicated a section of the journal to ultrasound
editorial in the British Journal of Anesthesia in 2005,
guided blocks, and an entire edition to review of
wrote thus - “successful regional anesthesia depends
evidence in favor of ultrasound guidance for blocks.
on deposition of the right drug, in the right dose, in
the right place!”. In pursuit of this simplistic goal, The Basics of Ultrasound
practitioners of regional anesthesia used landmark
Complex details of ultrasound physics and
based, and paresthesia seeking techniques to begin
machines are beyond the comprehension of the
with. Later, in an effort to improve success rates,
author, and the purview of this article. We anesthetists
peripheral nerve stimulation to elicit twitch of a muscle
need to know basic physics pertaining to ultrasound
supplied by the nerve that is to be blocked, was
image generation, image optimization, and image
employed. Instances of block failure, either despite
interpretation. We also need to know that ultrasound
muscle twitch, or failure to elicit the muscle twitch,
machines have transformed from being bulky and
even with peripheral nerve stimulation persisted,
cart-based, to sleek, light-weight and hand held.
giving credence to limitations with this guidance
technique. The advent of ultrasound, as a guidance • Any sound exceeding 20,000 Hz is ultrasound
tool, has redefined the practice of regional anesthesia • Ultrasound is mechanical sound energy that is
owing to the ability to visualize nerves and surrounding transmitted through a medium as a longitudinal
structures, the advancing needle, and the spread of wave with alternating areas of compression and
local anesthetic solution in real time. rarefaction
History
La Grange and colleagues were the first to
use an ultrasonographic blood flow detector to
locate the subclavian artery for the performance of
a supraclavicular brachial plexus block in 1978. As
ultrasound technology at that time was limited, this
was, however, an indirect application. The first reported
series of direct visualization of the suprclavicular
brachial plexus was by Stephen Kapral et al, in 1994.
Thereafter, significant improvements in technology
spurred the popularity of ultrasound amongst the • Piezoelectric crystals that line the patient end of
anesthetic community for peripheral nerve blockade, the transducer, upon stimulation by an electric
and, at present, for neuraxial blocks as well. charge, generate the ultrasound wave
There has been a surge in publications of
ultrasound guidance for various peripheral and
central neuraxial blocks, in adults and children, and
also parturients. The Regional Anesthesia and Pain
Medicine Journal, the official publication of the ASRA

• Resolution is the ability of the machine to

differentiate two closely related structures as
distinctly separate
• Time Gain Compensation (TGC) amplifies

returning echoes from deeper structures so as
to present a homogenous image
• Optimisation of image includes selection of the

right transducer (high frequency for superficial
• Properties of ultrasound waves include frequency, nerves, and low frequency, for deeper nerves),
measured as Hertz, wavelength, velocity of the adequate sterile gel / betadine / saline for
sound wave (velocity is least in air, low in liquids, acoustic coupling, adjusting ‘focus’, gain and
and highest in solids), and amplitude depth
• Doppler is a principle that permits quantification

of blood flow in vessels
• Modes of imaging include A(Amplitude)- Mode

(hardly used currently), M(Motion)- Mode, and
the B(Brightness)- Mode. The B - Mode is most
commonly used
• As waves travel deeper into biological tissue, Needle insertion & transducer manipulation
they are ‘attenuated’, i.e. lose heat. Higher the
• The transducer is rendered sterile before placing
frequency, more the attenuation, therefore, lesser
the same in the field for performance of the
the penetration
block
It is important to remember that • The transducer is placed on the patients skin to
High frequency = high spatial resolution but limited ensure total contact to avoid ‘air’ artifact, while
depth of penetration applying the right ‘pressure’ so that there is no
Low frequency = greater depth of penetration but compression, or displacement of superficial
lower spatial resolution structures
• The transducer, both emits the ultrasound beam, • Basic movements of the transducer include
and receives the wave reflected from the imaged ‘Alignment’, ‘Rotation’, and ‘Tilting’ to visualize
tissue, also called the ‘echo’ the nerve, optimize the image, and to visualize
the advancing needle in real time
• The nerves can be viewed in transverse (short)

axis, or, in longitudinal (long) axis. For all practical
purposes, short axis imaging is used for nerve
blocks

Therapy) Joint Committee guidelines for ultrasound

guided regional anesthesia that were published in the
Regional Anesthesia and Pain Medicine Journal in
2009, this technology is particularly useful for patients
with:
• Obscure anatomical landmarks
• Suspected or established coagulopathy
• Neural pathology
• Severe extremity trauma

• The needle can be inserted in line with the
transducer beam (in plane technique), or at right The Joint Committee enlisted 10 tasks that are helpful
angles to the ultrasound beam (out of plane tech- in performing an ultrasound guided nerve block.
nique). These include:
• Visualize key landmark structures, viz. blood

vessels, muscles, fascia and bone
• Identify the nerves or plexus on short axis

imaging
• Confirm normal anatomy and recognize anatomic

variations
• Plan for a needle approach that avoids

unnecessary tissue trauma
• Maintain an aseptic technique with respect to the

transducer
• Follow the needle under real time visualization

Successful ultrasound guided nerve as it advances to the target
blockade depends on the acquisition of three core
• Consider a secondary confirmation technique,
competencies; first –‘know what to look for’, second
such as nerve stimulation
– ‘know what you are looking at’, and third – ‘know
where the needle tip is’. Knowledge of sonoanatomy • When the needle tip is presumed to be in the
and interpretation of ultrasound images can be learnt correct position, inject a small volume of local
through attending dedicated workshops, self study, anesthetic. If spread of solution is not visualized,
observing experts at work, and practice of scanning presume that the needle tip is either intravascular,
on self and volunteers. or out of the imaging plane
Ultrasound guidance for regional anesthesia • Ensure visualization of the entire volume of local
anesthetic while being injected
Ultrasound is used for anatomic evaluation
and to facilitate the performance of both peripheral and • Maintain traditional safety guidelines, viz. pres-
neuraxial blocks. As per the ASRA (American Society ence of resuscitation equipment, frequent aspira-
of Regional Anesthesia & Pain Medicine) and ESRA tion, intravascular test dosing, standard monitor-
(European Society of Regional Anesthesia & Pain ing and patient response, during the procedure

COMMONLY PERFORMED NERVE BLOCKS WITH ULTRASOUND GUIDANCE

------------------------------------------------------------------------------------------------------
Upper Extremity Lower Extremity Other
------------------------------------------------------------------------------------------------------
Interscalene Post. Lumbar Plexus Ilioinguinal
Supraclavicular Femoral Iliohypogastric
Infraclavicular Saphenous Rectus Sheath
Axillary Gluteal Sciatic Neuraxial-Spinal
Mid-humeral Subgluteal Sciatic Neuraxial-Epidural
Forearm-Median Sciatic-Popliteal Neuraxial-Caudal
Forearm-Ulnar Common Peroneal Pediatric Blocks
Forearm-Radial Tibial Paravertebral
Suprascapular Ankle-Tibial Sympathetic Ganglia
Blocks
Deep Cervical Ankle-Deep Peroneal Trigger Point Injections
Ankle-Sural
Ant. & Post. Obturator
----------------------------------------------------------------------------------------------------
Advantages: Sheath and Transverse Abdominis Plane (TAP)

blocks in neonates and infants are being performed
Ultrasound guided regional blocks are superior in
with greater ease under visualization, and add a new
that:
dimension to post operative analgesia, especially
• Block onset time is faster when caudal block is contra indicated, as in the case
• The quality of block is better of spinal dysraphism. Ultrasound guidance for regional
blocks in pediatric patients offer precision, safety and
• Complication rates are lower
operator comfort.
• Time for block decreases with practice
Of late, there has been increasing interest in
• Lower volumes of local anesthetic required ultrasound assistance for neuraxial blocks. Though
anesthetists are more proficient with performance of
• More effective as teaching tool
neuraxial blocks when compared to peripheral nerve
• Improves practice of regional anesthesia blocks, the procedure is essentially ‘blind’, and, when
• Improves acceptance by surgeons and patients faced with a difficult back, failure and complications
ensue. Pre procedural scanning with ultrasound of
In pediatric patients, the challenges of regional the lumbar spine provides valuable information for the
anesthesia include injection into perineural spaces placement of spinals and epidurals, by determining:
in close proximity to vital structures such as veins,
arteries, and pleura etc, performance of procedure • The exact inter space at which the puncture will
under general anesthesia/sedation masking warning be performed
signals, and the need to limit local anesthetic volumes • The ideal inter space (clear sono anatomy)
to less than toxic doses. The small body surface area
• The midline of the inter space
in these patients lends itself to excellent scanning
images of relatively superficial structures by high • The angle of insertion
resolution ultrasound probes specifically designed for
• The depth to epidural space
use in pediatric population. This advantage applies
also to neuraxial blocks in this age group. Rectus • Any spinal abnormalitites

In 2008, the National Institute for Health and training with ultrasound and increasing publications
Clinical Excellence (NICE) in the UK issued guidelines will decrease traditional dependence on fluoroscopy
regarding the placement of epidurals under ultrasound and CT guidance.
guidance. Thomas Grau et al, in various publications
Over the years, ultrasound machine resolution
over a span of ten years, established the accuracy
has improved, machines have become smaller, hence,
of ultrasound in estimating depth to the epidural
easily transportable, and costs have been dropping as
space from the skin, in parturients, and the overall
a result of competition and enhanced patronage by the
reduction in both the number of attempts, and needle
anesthetic community. Though the capital investment
redirections while performing epidurals.
of the ultrasound machine is higher in comparison
With regard to interventional procedures in chronic to the peripheral nerve stimulator, due to improved
pain medicine, ultrasound has the obvious advantage block ergonomics, running costs are comparable. In
over fluoroscopy due to absence of ionizing radiation addition, the ultrasound machine can be utilized by
to both clinician and patient. Reports suggest that the anesthesiologist for central venous cannulation,
ultrasound guidance for selective cervical root block arterial cannulation, transthoracic echocardiograms
and stellate ganglion block are superior. With practice, (eyeballing), lung ultrasound (as per the blue protocol
injection of facet joint, paraspinal injections of the advocated by Dr Lichtenstein), and FAST (Focused
lumbar spine, sacroiliac joint, pyriformis muscle and Assessment with Sonography for Trauma).
pudendal nerve injections will be facilitated. Formal

WORKSHOPS


Advanced Trauma Life Support 261
01 ADVANCED TRAUMA LIFE SUPPORT
T V Ramakrishnan
Initial management and resuscitation of trauma • Lack of definitive diagnosis should never impede
patients the application of an indicated treatment
Trauma is a leading cause of death in the first • A detailed history is not a prerequisite to begin
four decades of life. The trauma team can play a ma- the evaluation of an acutely injured patient.
jor role in reducing the incidence of death in trauma The main steps in the early management of trauma
patients. are
Death from trauma has a trimodal distribution • Primary survey
First peak (non-salvageable) • Resuscitation (a & b go hand-in-hand)
Death occurs within seconds to minutes and is • Reassessment of ABC
usually due to laceration of the brainstem, heart, aorta
• Secondary survey
and other large vessels. Salvage after injury in this
instance is difficult and possible only in urban settings The team
with large well-equipped hospitals. Local facilities and staffing will determine the mem-
Second peak (salvageable) bership of the trauma team. An ideal trauma team
consists of the following members:
Death occurs within minutes to hours due to
diverse injuries such as SDH, hemopneumothorax, • Trauma Team Leader
splenic lacerations, fractures and significant blood • Airway doctor
loss. This group comprises of a large number of sal-
• Procedure / circulation doctor
vageable patients. The focus of this course will es-
sentially be on the management of these patients. • Airway nurse
Third peak • Procedure / circulation nurse
Death occurs from days and weeks after the ini- • Scribe nurse
tial injury and is due to sepsis, multiple organ failure. • Orthopaedic registrar
Advances in ICU management and improvement in
• Ward person
management will bring down the mortality rate in this
group. • Radiographer
Certain basic principles need to be clearly un- • Social Worker
derstood in the early management of trauma. The team should assemble in advance of the pa-
• Treat the greatest threat to life first tient’s admission and check all necessary equipment
and medications.

• Deterioration in the emergency department.

• Age >70 years with chest injury.
• Pregnancy >24 weeks with torso injury.
Mechanism / history
• Motor vehicle crash with ejection.
• Pedal cyclist, motorcyclist or pedestrian hit by
vehicle >30 km/h.
• Fall >5 metres.
• Fatality in same vehicle.
• Interhospital trauma transfer meeting activation
criteria.
Universal precautions
All persons attending a trauma call are obliged
to fully protect themselves, wearing eye protection,
gloves, mask and appropriate gowns. Adequate eye
Trauma team activation criteria
protection means wearing a curved eye shield or full
Criteria are based on specific anatomical injuries facial shield. Both should be available in the resuscita-
and physiological parameters that indicate actual in- tion area. Eyeglasses alone are not adequately protec-
stability or mechanism of injury that identifies a patient tive. Disposable fluid-resistant gowns must be used to
at high risk. A certain number of “false alarms” are protect body and clothing from fluid contamination and
required to ensure that potentially unstable patients or splashes. If contaminated, they must be thrown away.
patients with occult injury are not under triaged. Gloves must be used as with all other patient contact.
Anatomical Hypoallergenic gloves should be available for those
with a latex allergy.
• Injury to two or more body regions.
All blood and body fluids should be considered as
• Fracture to two or more long bones.
being infectious. All precautions must be in place before
• Spinal cord injury. attending a patient. Barrier protection is an individual
responsibility and the trauma team leader must also
• Amputation of a limb.
ensure that team members are adequately protected.
• Penetrating injury to head, neck, torso, or proximal Those without adequate protection should not be per-
limb. mitted in the trauma bays. Occasionally, patients are
• Burns >15% BSA in adults, >10% in children or brought in after exposure to various chemicals and
airway burns. environmental hazards. This situation also mandates
careful attention to team member protection from
• Airway obstruction.
exposure to these potentially hazardous substances.
Physiological Special protective equipment (eg. filtration masks)
must be available in the resuscitation room for this
• Systolic blood pressure <90mmHg or pulse >130
purpose.
bpm.
All sharp wastes to be disposed in designated
• Respiratory rate <10 or >30 per minute.
containers immediately after use.
• Depressed level of consciousness.

Obtain immediate follow up in event of a needle • Noisy breathing is a good indicator for airway
stick/sharps or splash injury as per the hospital needle obstruction.
stick protocol.
If cervical spine injury is ruled out, a triple airway
Primary survey maneuver consisting of head tilt, chin lift and jaw thrust
should be performed with suctioning of the mouth to
The objective of a primary survey is to identify life
clear the airway. In unconscious patients an oropharyn-
and limb threatening injuries. The assessment is with
geal airway or endotracheal intubation may be required
the ABCDE.
with C-spine protection. Unintentional movement
A – Airway with in-line cervical spine immobilisa- of the cervical spine during orotracheal intubation is
tion minimised by in-line stabilisation of the neck, provided
B – Breathing by the assistant.
C – Circulation with hemorrhage control Neck
D – Disability (neurological status, as expressed Once the airway is made patent, the neck is
by the patient) quickly examined for wounds, tracheal positioning,
venous distention, surgical emphysema and crepitus.
E – Exposure of the entire body (looking for oc- Then the C-spine is stabilised with semi-rigid collar,
cult injury) sand bags and tape.
Resuscitation “A clear distinction must be made between ad-
Resuscitation is the step that is performed when equate airway and adequate breathing”.
any component of primary survey appears unstable. B - Breathing and Ventilation
A - Airway with cervical spine protection Airway patency alone does not ensure adequate
• Patency of the airway is assessed first by looking ventilation. Adequate gas exchange is mandatory. If
for foreign bodies, facial and mandibular fractures the patient cannot maintain adequate tissue oxygen-
or tracheal / laryngeal injuries that may result in ation in spite of adequate O2 then artificial ventilation
airway obstruction must be instituted. Inspection, palpation and ausculta-
tion of the patient’s chest are to be followed as the type
• Cervical spine injury must be suspected in all
of breathing pattern can provide clues about the pres-
cases of trauma especially with an altered level
ence of injury. Some common causes of inadequate
of consciousness or evidence of injury above the
ventilation are:
level of the clavicle.
Bilateral Unilateral
1. Obstruction of the upper respiratory 1. Intubation of right main bronchus

tract 2. Pneumothorax
3. Hemothroax
2. Leak between face and mask 4. Foreign body in main bronchi
5. Lung contusion
The immediate life threatening thoracic conditions must centesis in the 2nd intercostal space using 14
be noted and treated immediately. G needle
• Airway obstruction - must be relieved • Open chest wounds – must be dressed
• Tension pneumothorax – needle thoraco- • Massive hemothroax – chest drain in 5th

intercostal space anterior to the mid-axillary pressure, decreased urine output, decreased level of
line. consciousness.
• Flail chest - internal pneumatic fixation by • External pressure is applied to obvious sites
intubation and positive pressure ventilation / of bleeding
operative fixation of ribs.
• Two wide bone 14-16 G peripheral lines should
C - Circulation and hemorrhage control be started immediately
Haemorrhage is the predominant cause of death • Tourniquets should not be used except in
in trauma. “Treatment of bleeding is to control it”. traumatic amputation of an extremity
Observations that provide information about the circula-
• An initial fluid bolus of 2L of NS can be rushed
tory status are increased pulse, increased respiratory
and the patient’s condition reassessed.
rate, increased capillary refill time, skin pallor, cold and
clammy extremities, decreased BP, decreased pulse • If hypotension persists then blood must be
administered.
Responses to fluid resuscitation
Parameters Rapid response Transient response No response

Vital Signs Return to normal Transient Remain abnormal
improvement
Recurrent of 3 BP &
1 HR
Estimated blood Minimal (10-20%) Moderate & ongoing Severe (>40%)
loss (20-40%)
Need for more Low High High
crystalloids
Need for blood Low Moderate to high Immediate
Blood preparation Types & cross match Type specific Emergence blood
release
Need for operative Possibly Likely High Likely
intervention
The patient’s response to initial fluid resuscita- An altered level of consciousness indicates the
tion is the key to determining subsequent therapy. need for immediate re-evaluation of the patient’s oxy-
genation, ventilation and perfusion status. If hypoxia
D - Disability
and hypovolemia are excluded, changes in level of
A rapid neurological evaluation should be per- consciousness should be considered to be of trau-
formed as a part of the primary survey. The level of matic CNS origin until proved otherwise.
consciousness is assessed using the AVPU scale.
E - Exposure & Environment
Detailed neurological examination is reserved
for the secondary survey. Exposure of the entire body is required to look
for any occult blood. Prevent hypothermia by cover-
A – Alert
ing the patient with warm blankets after examination.
V – Response to verbal stimuli
Indications for a definitive airway
P – Response to pain
Airway : Obstructed airway, inade-
U – Unresponsive quate gas reflex

Breathing : Inadequate breathing O2 sat- It may well be said that secondary survey is
uration less than 90% “tubes and fingers in every orifice”
Circulation : Inadequate circulation, sys- History

tolic BP<75mmHg despite A detailed history consisting of
adequate fluid resuscitation.
A – Allergies
Disability : Coma, GCS < 8/15
M – Medications
Environment : Hypothermia, core temp < 330 C
P – Past medical history / pregnancy
Resuscitation
L – Last meal
Aggressive resuscitation and management of
Head & face
life threatening injuries as they are identified are es-
sential to maximize patient survival. The adequacy of Scalp lacerations are probably the commonest
resuscitation is monitored by head injury seen in the emergency department. They
tend to bleed profusely because of abundant vascu-
Airway : Pulse oximetry / capnography
lar supply. Apply direct pressure to control any bleed-
Breathing : Respiratory Rate / ABG / capnog- ing. Check the continuity of the cranium with a gloved
raphy hand, palpating gently with the fingertips. Be aware
Circulation : Assessing perfusion by BP / pulse of small puncture wounds of the scalp, which may in-
dicate penetrating injury of the brain.
/ temp / CVP / urine output
The Glasgow Coma Scale (GCS), a frequently
Disability : Pupils / AVPU, GCS
used neurological assessment tool is currently con-
Environment : Core temperature sidered ideal for documenting and monitoring head
Secondary survey injured patients. The nose & ears are assessed for
bleeding and leaking of CSF. Inspect the mouth for
Does not begin until the primary survey (ABCDE) lacerations, broken teeth, vomitus or conditions that
is completed, resuscitative efforts are well-established have the potential to compromise the airway. The
and the patient is demonstrating normalisation of vital neck is immobilised until cervical spine films are re-
signs. ported as normal.
The secondary survey is a systemic comprehen- Thorax
sive evaluation of all organ failure.
Examination of the thorax is done by review-
These include: ing the findings of the primary survey. Auscultate
• A detailed medical history for breath sounds high on the anterior chest wall for
pneumothorax and posterior bases for hemothroax. If
• Head to toe evaluation intubated check endotracheal tube placement. Inter-
• Complete neurological examination costal drainage tubes may be necessary in the pres-
ence of pneumo / hemothorax.
• Investigations like focussed assessment with
sonography for trauma / diagnostic peritoneal Abdomen
lavage (FAST / DPL) A thorough examination is done by inspection,
• Radiological evaluation palpation, percussion and auscultation. Exposed
bowel is covered with warm saline soaked swabs to
• Laboratory studies avoid hypothermia and fluid loss.
• Formulate management plan Focussed assessment with sonography for
trauma FAST and Diagnostic peritoneal lavage (DPL)

help us to assess the type and severity of injury and Signs of spinal cord Injury
plan further management.
• Hypotension and bradycardia
Signs of uretheral Injury
• Decreased motor power and sensation below
Presence of blood at external urethral meatus, the lesion
bruising of scrotum or perineum and a high riding
• Decreased anal sphincter tone
prostate.
• Priapism
Signs of renal Injury
They may present event without any other signs
Flank pain, flank mass, flank bruising and hema-
of external injury
turia.
The compensatory mechanism in patients with
Signs of liver and splenic injury
hypovolemic shock like tachycardia and peripheral
Fracture of lower ribs on the right side may indi- vasoconstriction are absent in patients with spinal
cate liver injury and on the left side splenic injury. Pa- cord injuries. This is because of loss of sympathetic
tient will be hemodynamically unstable and abdominal tone as well as disruption of the cardio accelerator
tenderness will be present. fibers.
Rectal examination Pain relief
Sphincter tone, presence of rectal damage, pel- The relief of pain is an important aspect in trauma.
vic fractures, prostate position and blood in faecal Intramuscular injections must be avoided. Judicious
residue are all to be noted. use of IV narcotics and anxiolytics are recommended
to achieve the desired level of patient comfort and re-
Extremities: Long bone fractures can cause consid-
lief of anxiety while avoiding respiratory depression,
erable blood loss. Fracture of femur and humerus
the masking of subtle injuries or changes in patient’s
can cause 1.5 to 2 litres of blood loss.
status.
• Palpate for tenderness, crepitus and deformi-
Revised trauma score
ties.
Helps to quickly assess the severity of injury.
• Quality and integrity of pulses distal to the frac-
Adding scores of systolic BP, GCS and respiratory
ture site are noted to rule out vascular injuries
rate gives us the RTS.
• Suspected fractures and dislocations are splint-
ed for reducing pain and for further radiographic
and diagnostic evaluation.
Revised trauma score
Score Systolic BP GCS RR
4 >90 13-15 10-29

3 76-89 9-12 >29
2 50-75 6-8 5-9
1 1-49 4-5 1-4
0 0 3 0

Interpretation notes (chart) are the critical link that allows each carer
to know the plans of each involved consultant. Without
• Normal - > 12
detailed notes, care can become fragmented - creat-
• Significant injury - <9 ing delays, errors and potentially increasing patient
• Moribund - 0 morbidity.
• Lesser the score, poorer is the outcome • Ensure all notes in the patient’s chart are written
clearly with a detailed plan for investigations and
Resuscitation room documentation treatment.
All members of the trauma team must carefully • Write the date and time with each note.
make notes regarding injuries found and interventions
required during the resuscitative phase of care. The • Contact subspecialty consultants directly if there
trauma team leader completes the detailed trauma as- is conflict or confusion about another team’s plan
sessment form based on information obtained during for investigations or management.
primary and secondary surveys. The surgical registrar • Write down laboratory results in the notes.
makes detailed notes and diagrams of injuries found
• Ensure all radiographs are reviewed and note the
during the secondary survey and makes additional
name of the consultant radiologist who reviewed
notes about any interventions required.
them along with the results in the patient notes.
The other critical information gatherer is the scribe Others will then not need to waste their time and
nurse who makes detailed notes whilst the resuscita- that of another (or the same) radiologist to learn
tion is in progress. The details and times is a critically the same thing.
important element of trauma care. Accuracy, speed and
Summary
detail are absolute requirements. It is important that the
trauma team leader reviews all information at the end The injured patient must be evaluated rapidly
of the secondary survey including the trauma series of and thoroughly. The doctor must develop treatment
x-rays and, after reviewing the findings with the trauma priorities for the overall management of the patient, so
registrar, trauma fellow and any subspecialty consul- that no steps in the process are omitted. An adequate
tants, formulates and documents a detailed plan for patient history and accounting of the incident are impor-
patient investigation and care. Whilst recognising that tant in evaluating and managing the trauma patient.
trauma care is a dynamic process and priorities change
Bibliography
based on changes in the patient, it is still important to
document these changes and the consequent changes • Advanced Trauma Life Support for Doctors. In-
to a plan of investigation or treatment. Good trauma structor Course Manual Book 1 - Seventh Edition,
patient care and management often requires input and 2005, American College of Surgeons, Chicago
treatment from numerous subspecialists. The patient’s • Comprehensive Trauma Life Support for Doctors
2010

Perioperative Arrhythmias 268
01 PERIOPERATIVE ARRHYTHMIAS
Raju P S N, Ranjith Karthekeyan B

Thamarai, Harishbabu
Cardiac arrhythmias are a significant cause of manifestation of their heart disease. The addition of
morbidity and mortality in the perioperative period. The transient imbalance (e.g., ischemia, catecholamines, or
incidence of intraoperative dysrhythmias depends on electrolyte abnormalities) may be all that is necessary
the definition (e.g., any dysarrhythmia vs. only poten- to trigger lethal ventricular tachydysrhythmias.
tially dangerous ones), continuous surveillance versus
Diagnosis of dysrhythmias
casual observation, patient characteristics, and the
nature of surgery. While the incidence of perioperative The first principle in managing arrhythmias is to
arrhythmias is extremely high (up to 70% ), only 1.6% of treat the patient rather than the electrocardiogram.
these will require clinically significant management(1). Accordingly, one must first decide whether the prob-
lem is an arrhythmia or an artifact and whether the
Physiologic Impact
cardiac rhythm is sufficient to account for the patient’s
The ventricular rate and duration of tachydys- problem. The next step is to establish the urgency of
rhythmias and myocardial functional impairment are treatment. Clinical assessment includes evaluation of
the most important factors determining outcomes. pulse, blood pressure, peripheral perfusion, and the
Rapid ventricular rates with tachycardia can cause presence of myocardial ischemia and congestive heart
diastolic encroachment, reduce cardiac output, and failure. If the patient loses consciousness or becomes
result in hypotension or myocardial ischemia. Chronic hemodynamically unstable in the presence of a tachyar-
tachycardia may produce cardiomyopathy and cardiac rhythmia other than sinus tachycardia, prompt electrical
failure. Bradydysrhythmias, especially with loss of atrial cardioversion is indicated. If the patient is stable, there
transport function, may impact severely on patients with is more time to establish the diagnosis and decide on
systolic or diastolic ventricular dysfunction. Cardiac out- the most appropriate course of treatment.
put more than doubled after atrial pacing for overdrive
The goals of antiarrhythmic therapy depend on
suppression of AV junctional rhythm (AVJR) in some
the type of rhythm disturbance. The initial goal must
patients with presumed left ventricular dysfunction(2).
always be to establish hemodynamic stability. The first
Genesis of dysrhythmias treatment of tachyarrhythmias is to slow the ventricular
response. In the case of problematic bradyarrhythmias,
Perioperative dysrhythmias are more likely to
ventricular rate must be increased. The next goal is to
occur in patients with structural heart disease (WPW
restore sinus rhythm, if possible. If restoration of sinus
syndrome, congenital and valvular heart disese,
rhythm cannot be achieved, prevention of complica-
myocardial infarction, and cardiomyopathies) and the
tions becomes an issue.
initiating factor is often transient imbalance (electrolyte
or metabolic imbalance, tracheal intubation, ischemia, Tachyarrhythmias are usually classified according
hypoxia, hypercarbia, and central vascular catheters). to anatomical origin, as supraventricular or ventricular.
Therefore, structural heart disease and imbalance Supraventricular arrhythmias include sinus tachycardia,
provide a substrate for reentry, triggered activity, or atrial flutter and fibrillation, ectopic atrial tachycardia,
abnormal automaticity(3). For example, patients with multifocal atrial tachycardia, junctional tachycardia,
chronic coronary artery disease have elements of atrioventricular (A-V) nodal reentrant tachycardias, and
normal and abnormal conduction interacting with non- accessory pathway reciprocating tachycardias. Ventric-
uniform myocardial refractoriness. They also may have ular arrhythmias consist of premature ventricular beats,
occasional or frequent ventricular extrasystoles as a ventricular tachycardia, and ventricular fibrillation. It is

useful to consider tachyarrhythmias from a treatment 2. Establish the relationship between the P Wave
standpoint, dividing them into those that traverse the and QRS Complex
A-V node and those that do not. Tachyarrhythmias tra-
If there are more P waves than QRS complexes,
versing the A-V node include atrial flutter and fibrillation,
then A-V block is present. If there are more QRS
automatic (ectopic) atrial tachycardia, multifocal atrial
complexes than P waves, the rhythm is junctional
tachycardia, A-V nodal reentry, and A-V reciprocating
or ventricular in origin. If the relationship is 1:1, then
tachycardias. Tachyarrhythmias that do not traverse
measurement of the PR interval (or RP interval) can
the A-V node include preexcited atrial arrhythmias
provide useful diagnostic clues.
(with antegrade conduction through a bypass tract),
ventricular tachycardia, and ventricular fibrillation. The 3. Examine the QRS morphology
clinical import of this classification is that the ventricular A narrow QRS complex (>0.12 msec) indicates
response of the tachycardias which traverse the A-V a supraventricular arrhythmia. A wide QRS complex
node can be controlled by pharmacologically altering can be present with either ventricular tachycardia or
A-V nodal conduction. When the arrhythmias do not supraventricular tachycardia with preexisting bundle-
use the A-V node, drugs that slow A-V nodal conduc- branch block, aberrant ventricular conduction, or ante-
tion can be dangerous. grade conduction via an accessory A-V connection.
Tachycardia diagnosis: A 12-lead electrocardiogram 4. Search for other clues
with a long rhythm strip and a previously obtained
The clues to look for depend on the situation.
12-lead electrocardiogram for comparison are ideal;
Carotid sinus massage (and other vagal maneuvers)
barring that, a long rhythm strip of a lead in which P
increase A-V block and can either break a supraven-
waves are visible is preferred. The approach can be
tricular tachycardia or bring out previously undetected
outlined by using the following four steps. A systematic
flutter waves. Any patient with a ventricular rate of
approach to electrocardiographic (ECG) diagnosis can
exactly 150 beats/min should be suspected of having
improve the accuracy and likelihood of success with
atrial flutter with 2:1 A-V block. A rate >200 beats/min
subsequent management.
in an adult should raise the suspicion of an accessory
1. Locate the P Wave pathway. In the presence of a wide complex tachy-
Is a P Wave Visible? If no P waves are present cardia, A-V dissociation is diagnostic of ventricular
and the QRS complexes are irregular, the rhythm is tachycardia. Capture beats (supraventricular conduc-
most likely atrial fibrillation. A regular narrow QRS tion with a narrow QRS complex) make aberration
complex tachycardia without discernible P waves is unlikely and favor a ventricular origin of wide QRS
most likely caused by A-V nodal reentry. Recordings complexes. The presence of fusion beats (which result
obtained from esophageal or intracardial leads can from simultaneous ventricular activation via ventricular
provide useful information about atrial activity. How fast and supraventricular sources) likewise suggests ven-
are the P waves? In adults, sinus tachycardia usually tricular tachycardia. Certain QRS morphologies favor
occurs at a rate between 100 and 180 beats/min. Atrial ventricular tachycardia over aberration.
tachycardias and A-V nodal reentrant tachycardias Pharmacologic management
usually present with rates from 140 to 220 beats/min.
Antidysrhythmic action
Rates between 260 and 320 beats/min are most likely
to represent atrial flutter. Cellular mechanisms for clinical cardiac dys-
rhythmias include altered normal automaticity of pri-
What is the morphology of the P Waves? Normal
mary and latent pacemakers, abnormal automaticity
P waves are upright in leads I, II, aVF, and V4-V6. Au-
in partially depolarized fibers, triggered activity from
tomatic atrial tachycardia often presents with negative
early or delayed after depolarizations, and reentry.
P waves in one or more of these leads.
Antidysrhythmic drugs oppose these mechanisms by

altering pacemaker currents, reducing intracellular Examples of perioperative dysrhythmias with likely
Ca2+ overload, affecting Ca2+ plateau or K+ repolariza- mechanism, desired antidysrhythmic drug action, and
tion currents, or producing alterations in conduction useful drugs are listed in table 1.
and refractoriness that are nonconductive to reentry.
Table 1: Examples of perioperative dysrhythmias with likely mechanism, desired antidysarhythmic drug
action, and useful drugs
CCB=calcium channel blockers (diltiazem, verapamil), AChE=anticholinesterase inhibitors (edrophoni-

um), DAD/EAD=delayed/early afterdepolarizations, VT=ventricular tachycardia. * By reversing coronary
spasm and/or opposing calcium current contributing to pacemaker potential. † Not if patient is known to
have ventricular preexcitation. ‡ Temporary pacing is safe and more reliable.
Antiarrhythmic drugs tential, and Class Ic (flecainide, propafenone) do not

affect the duration of the action potential.
Drugs that modify the rhythm and conduction of
the heart are used to prevent cardiac arrhythmias. All Class II drugs
such drugs may aggravate or produce arrhythmias These antisympathetic drugs prevent the effects
and they may also depress ventricular contractility of catecholamines on the action potential. Most are
and must, therefore, be used with caution. There are β-adrenergic antagonists. Cardioselective β-blockers
more than 30 antiarrhythmic drugs. They are classi- (β1) include metoprolol, atenolol, and acebutalol.
fied according to their effect on the action potential
Class III drugs
(Vaughan Williams’ classification). Dosing, indica-
tions, and precautions for these specific parenteral These prolong the action potential and do not af-
drugs used for acute management of dysrhythmias fect sodium transport through the membrane. There
are summarized in Table 2 & 3. are two major drugs in this class; amiodarone and so-
talol. Sotalol is also a β-blocker.
Class I drugs
Class IV drugs
These are membrane-depressant drugs that re-
duce the rate of entry of sodium into the cell. They The non-dihydropyridine calcium antagonists
may slow conduction, delay recovery or reduce the that reduce the plateau phase of the action poten-
tial are particularly effective at slowing conduction in
spontaneous discharge rate of myocardial cells. Class
nodal tissue. Verapamil and diltiazem are the most
Ia drugs (e.g. disopyramide) lengthen the action po-
important drugs in this group.

Table 2: Specific antidysrhythmic drugs suitable for parenteral use in acute dysrhythmia management,
along with Vaughan Williams class action, dosing, indications, and precautions.
PSVT=paroxysmol supraventricular tachycardia, WPW= Wolff Parkinson White syndrome, AV=atrio

ventricular, SND=sinus node dysfunction, CLQTS=congenital long QT interval syndrome, Sch= succi-
nylcholine, COPD= chronic obstuctive pulmonary disease.

Table 3: Suggested doses, indications, and precautions for miscellaneous drugs that can be adminis-
tered iv for diagnosis or management of perioperative dysrhythmias.
PSVT=paroxysmol supraventricular tachycardia, WPW= Wolff Parkinson White syndrome, AV=atrio

ventricular, CAD= coronary artery disease, GI=gastrointestinal, SND=sinus node dysfunction,
CLQTS=congenital long QT interval syndrome, BB, CCB=β or calcium channel blockers.
Pacing and cardiac electroversion Temporary cardiac pacing
Cardiac pacing and electroversion (cardiover- Epicardial, transvenous (endocardial), transcuta-

sion or defibrillation) have advantages over drugs for neous, and transesophageal routes are used for tem-
the management of perioperative dysrhythmias. Their porary pacing. Epicardial, endocardial, or transesopha-
therapeutic effect is more prompt, and the “dose” (i.e., geal leads are also useful for ECG diagnosis because
of their proximity to myocardium. Epicardial, atrial,
pacing mode, rate, current) is easier to titrate than
ventricular, or dual‐chamber pacing is used in cardiac
with drugs. Also, drugs may not produce the desired
surgery to increase heart rate, suppress bradycardia-
effect or aggravate dysrhythmias. Finally, drug effects
dependent tachycardia, overdrive escape rhythms,
may last longer than required. Nonetheless, there are suppress atrial or ventricular extrasystoles, and to
recognized disadvantages to pacing, including risk of terminate reentrant SVT or atrial flutter(4). Atrial or
sepsis, hemorrhage, or direct myocardial injury with dual‐chamber is preferred to ventricular pacing to
invasive methods, stimulation of tachydysrhythmias, preserve atrial transport function. Endocardial atrial,
and inability to pace some patients. ventricular or dual‐chamber pacing is used for most
other temporary pacing.

Noninvasive transcutaneous pacing (TCP) is used pause, sino‐atrial block, and sinus arrest. These
if invasive pacing is not feasible or is impractical. Cur- rhythms may produce symptoms or result in the emer-
rent adult advanced cardiac life support guidelines gence of alternative pacemakers, producing a variety
emphasize early use of TCP in emergency cardiac of ECG observations, including wandering atrial pace-
care, but results are discouraging when not instituted maker or paroxysmal atrial tachycardia. In perioperative
early after cardiac arrest. Limitations include 1) non- settings, these disturbances are often transient and
physiologic (ventricular) pacing, 2) inability to capture often caused by autonomic imbalance as the result
in some patients, 3) restricted access (sterile fields, pa- of an intervention (spinal or epidural anesthesia, lar-
tient position), and 4) discomfort in conscious patients. yngoscopy, surgical stimulation, and so on) or by the
Transesophageal (TE) pacing probes are approved for effects of drugs on the sinus node or perinodal tissue.
atrial pacing. These rhythms require management if bradycardia
compromises end‐organ perfusion. β1 agonists are
Cardiac electroversion
more reliable and longer acting than antimuscarinic
Cardiac electroversion includes cardioversion agents for increasing rate. Cardiac pacing is effective
(synchronized shocks) and defibrillation (nonsyn- and may be initiated by either the transesophageal or
chronized shocks). Both use high‐energy capacitor transvenous route(5). Patients scheduled for surgery
discharges to simultaneously depolarize a sufficient who are known to have symptoms attributable to
mass of myocardium to terminate dysrhythmias. Car- bradydysrhythmias associated with SND may have
dioversion is not indicated for automatic or triggered a prophylactic temporary pacemaker inserted before
tachydysrhythmias (especially with digitalis) because induction of anesthesia.
it merely resets the cycle of automaticity or triggered
Management of the combination of bradycardia
activity and may initiate VF. The lowest possible energy
with paroxysmal tachydysrhythmias (bradytachy syn-
shocks should be used to reduce the risk of myocardial
drome) is more challenging. Chronotropic drugs used
injury. External shocks of 25–50 J (internal, 5–20 J) will
to manage or prevent bradycardia may aggravate or
terminate most SVT or VT, although 50–200 J (internal,
produce more frequent episodes of sinus tachycardia
10–50 J) is needed for atrial flutter‐fibrillation. Current
or tachydysrhythmias (often atrial flutter or fibrillation).
for defibrillation (external, 200–360 J; internal, 5–50
Treatment in these patients may include a beta‐block-
J) is higher because far more myocardium should be
er for suppression of sinus tachycardia or appropriate
depolarized.
antidysrhythmic drug for tachydysrhythmias and a per-
Specific dysrhythmias manent pacemaker for management of bradycardia.
Patients requiring oral antidysrhythmics should Atrial tachycardia
be continued on therapy until the time of surgery.
Atrial tachycardia is a supraventricular tachycardia
Consultation is advised for patients who require
that originates in atrial muscle and does not include
pacing‐cardioverter devices (PCD) to suppress or
the sinus node or AV node. Uniform atrial tachycardia
terminate tachydysrhythmias. Initial management for
(UAT) is characterized by a single P‐wave morphol-
perioperative dysrhythmias does not differ from other
ogy, whereas multiform atrial tachycardia (MAT) has
acute circumstances. With life‐threatening circula-
three or more distinct P‐wave morphologies. Heart
tory compromise, prompt pacing or electroversion is
rates may range from 100–250 beats/min, and there
required. Obvious imbalance should be corrected and
may be rate‐dependent PR interval variation. Varying
management provided for underlying heart disease.
degrees of AV block may be present with fast heart
Specific antidysrhythmic drugs are used to suppress
rates, especially in patients receiving digitalis or other
dysrhythmias and prevent recurrences.
drugs that increase AV node refractoriness and con-
Sinus node dysfunction duction time.
Bradydysrhythmias associated with sinus node Postulated mechanisms for UAT and MAT are
dysfunction (SND) include sinus bradycardia, sinus similar and include enhanced normal or abnormal au-

tomaticity or triggered activity within the atrium. These paroxysmal supraventricular tachycardia (PSVT). Si-
mechanisms result in an incessant tachycardia with nus node and intraatrial reentry (mechanisms for PAT
variation in rate depending on autonomic tone. When discussed previously) account for the remainder. APs
reentry is the cause (UAT), onset and termination of are electrophysiologically similar to atrial muscle and
tachycardia are paroxysmal. can manifest or concealed. Manifested APs conduct
Management of atrial tachycardia is twofold. First, anterogradely during sinus rhythm to preexcite the
controlling the ventricular rate, and second, identifying ventricles (short PR interval, delta wave). Patients with
and removing the cause whenever possible. Short WPW syndrome have preexcitation and paroxysmal
bursts of tachycardia (unless very frequent) gener- tachycardias. Concealed APs conduct retrogradely
ally do not require specific drug management. When during orthodromic AP reentry tachycardia but not an-
definitive management is indicated, an intravenous terogradely to cause preexcitation. AP reentry accounts
beta‐blocker or CCB may be tried. These agents will for up to 80%, atrial fibrillation for 15–30%, and atrial
reduce the ventricular rate and may suppress tachycar- flutter up to 5% of tachydysrhythmias in patients with
dia. Unless caused by reentry, atrial tachycardias are WPW. 90 to 95% of AP reentry is of the orthodromic
not likely to be terminated by pacing or cardioversion. variety.
If digitalis intoxication is the cause, Fab antibodies are Paroxysmal supraventricular tachycardia caused
indicated. Amiodarone, flecainide, and magnesium by the common form of AV node and orthodromic AP
(especially with hypomagnesemia) have been reported
reentry is characterized by its abrupt onset after a
to terminate some types of atrial tachycardia.
premature beat of atrial origin. The P wave of the pre-
AV junctional rhythm disturbances mature beat initiating tachycardia usually has a different
morphology than those during tachycardia. PSVT also
AV junctional rhythm is a nonparoxysmal, narrow
terminates suddenly, often followed by a brief period
QRS rhythm with retrograde or nonapparent P waves
and a rate less than 70 beats/min. If faster, usually less of asystole or bradycardia. Finally, PSVT is a regular
than 130 beats/min, it is termed accelerated AVJR or tachycardia with rates between 120 and 300 beats/min,
nonparoxysmal AV junctional (or nodal) tachycardia. and most patients are children or young adults without
An important cause for accelerated AVJR is digitalis heart disease.
toxicity, recognized by regularization of the ventricular Paroxysmal supraventricular tachycardia in pa-
rate in patients with atrial fibrillation. Accelerated AVJR tients without syndrome: After vagal maneuvers,
occurs in up to 10% of patients with acute myocardial drugs that increase AV node refractoriness (adenosine,
infarction and also in patients having cardiac surgery or CCB, esmolol, and other beta‐blockers) are preferred
with acute rheumatic fever. Esmolol has been effective initial therapy for any narrow QRS PSVT or PAT result-
treatment in some patients having coronary revascular- ing from SA node or atrial reentry. With circulatory insuf-
ization, possibly because ischemia and catecholamines ficiency, prompt cardioversion is advised. Adenosine
contributed to AVJR. Atropine or ephedrine may restore is preferred by some for initial drug treatment of PSVT
sinus rhythm in some patients, although these drugs because it: 1) has efficacy comparable with CCB; 2)
may have no effect or may accelerate AVJR in others. is shorter‐acting; 3) does not cause cardiovascular
Therefore, temporary pacing is advised, especially
collapse or ventricular fibrillation if administered to
in patients with ischemic heart disease. AVJR and
a patient with VT or preexcited atrial tachycardia 4)
accelerated AVJR are suppressed by atrial or dual-
has little effect on AP in patients with orthodromic AP
chamber overdrive pacing. With increased coronary
reentry tachycardia; and 5) can slow retrograde AP
perfusion, it is usually possible to terminate pacing
or AV node conduction to terminate antidromic AV
within a short timespan.
reentry PSVT.
Paroxysmal supraventricular tachycardia
Narrow QRS paroxysmal supraventricular tachy-
AV node and accessory pathways (AP) reentry, cardia in patients with Wolff‐Parkinson‐White
in about equal proportions, account for 85–90% of syndrome: Caution is advised with using digitalis,

diltiazem, or verapamil as a single drug for initial treat- by diastolic encroachment and loss of atrial transport
ment of narrow QRS PSVT in patients known to have function. There is an approximate 5% annual risk of
the WPW syndrome. All can accelerate the ventricular thromboembolism in patients with paroxysmal or recent
rate with atrial flutter or fibrillation, and some patients onset (< 48 h) atrial fibrillation not receiving anticoagu-
will develop atrial flutter or fibrillation during treatment lant therapy. Patients at increased risk are those with
for orthodromic AP re-entry PSVT. Otherwise, initial rheumatic heart disease, sick sinus syndrome, mural
treatment is similar to that for PSVT in patients with- thrombi, left atrial enlargement, hypertension, left ven-
out WPW (i.e., vagal maneuvers, adenosine, beta- tricular dysfunction, and aged >75 yr. Anticoagulation is
blockers, and cardioversion). advised for 3 or 4 weeks before elective DC cardiover-
sion for all patients with atrial fibrillation of >2 days or
Wide QRS paroxysmal supraventricular tachycar-
unknown duration.
dia in patients with Wolff‐Parkinson‐White syn-
drome: Antidromic AP reentry PSVT is a preexcited Atrial pacing is not feasible in patients with atrial
(wide QRS) tachycardia with rates up to 250 beats/min. fibrillation. Ventricular pacing is used for those with
Differential diagnosis includes all other causes for wide deleterious bradycardia. DC cardioversion (usually
QRS tachycardia, including preexcited atrial tachycar- 100–200 J) is the most effective method to convert atrial
dias, any SVT with aberrant ventricular conduction, or fibrillation to sinus rhythm. It is most likely to be suc-
ventricular tachycardia. Intravenous procainamide or cessful with paroxysmal or recent onset atrial fibrillation
amiodarone are initial drugs of choice for termination and small heart size. Rarely are class Ia drugs used
of known antidromic AP re-entry PSVT or wide QRS for this purpose today, although they are prescribed to
tachycardia in a patient with patient, unless the patient prevent recurrences. Class Ic drugs, amiodarone, but
needs immediate cardioversion. not sotalol, are also effective for preventing recurrences
of atrial fibrillation (6).
Atrial Flutter
Beta‐Blockers, diltiazem, or verapamil, alone
Atrial flutter is a paroxysmal disturbance, usually
or with digoxin, are used for acute ventricular rate
lasting only minutes to hours before changing to sinus
reduction with atrial fibrillation. In patients with fast ven-
rhythm or atrial fibrillation. Flutter waves, best seen in
tricular rates and hemodynamic compromise, prompt
leads II, III, aVF, and V1, often have a saw‐tooth ap-
cardioversion is advised. Procainamide, amiodarone
pearance with no isoelectric line. The ratio of atrial to
flecainide, and propafenone are used to prevent recur-
conducted beats is either fixed or variable. Atrial flutter
rences. Any of these drugs may chemically convert
is seen commonly in patients with chronic pulmonary
some episodes of paroxysmal atrial fibrillation in those
disease, open heart surgery, dilated cardiomyopathy,
with WPW and in other patients (7).
inflammatory conditions affecting the heart, ethanol
intoxication, and thyrotoxicosis. With circulatory com- Ventricular premature beats and non‐sustained
promise, cardioversion (usually 50 J or less) or rapid tachycardia (NSVT)
atrial pacing (type I atrial flutter) is preferred initial
A distinction is made between ventricular prema-
management. Prophylaxis is achieved with class Ia,
ture beats (VPB), NSVT, and sustained VT (lasting
Ic or III drugs in diseased heart patients.
longer than 30 s). Sustained VT is usually a manifesta-
Atrial Fibrillation tion of structural heart disease, has an adverse hemo-
dynamic effect, and is managed with antidysrhythmic
Atrial fibrillation is paroxysmal or chronic and is
drugs or antibradycardia pacing to prevent recurrences.
the most common tachydysrhythmia in patients with
VPB and NSVT can occur without heart disease, often
the sick sinus syndrome. Other associations include
are hemodynamically inconsequential, and do not
hypertension, chronic pulmonary disease, coronary
necessarily require antidysrhythmic drug treatment.
and other structural heart disease, and after cardio-
thoracic surgery. Paroxysmal atrial fibrillation may be Suggested treatment priorities: When and how
poorly tolerated in patients with heart disease caused VPB or NSVT should be managed in perioperative

circumstances is uncertain, even for patients having because of possible hypotension with these drugs. With
cardiac surgery. Appearance and frequency of PVB circulatory collapse, immediate cardioversion followed
or NSVT are probably insufficient criteria on which to by intravenous lidocaine is recommended. The initial
base the decision to manage with antidysrhythmics. shock should be 200 J, followed by 300 and 360 J if
Other factors to consider are hemodynamic impact, necessary. If lidocaine suppresses SMVT after DC
underlying pathophysiology, adequacy of treatment for conversion, the drug should be infused continuously.
concurrent disease, and whether VPB or NSVT initiate If it fails to suppress SMVT, then bretylium or procain-
more ominous dysrhythmias. amide should be administered, followed by continuous
infusion of whichever drug is effective. For refractory
Treatment: Specific drug management for VPB or
cases, amiodarone should be considered.
NSVT is with beta‐blockers (especially with adrener-
gic stress), lidocaine, and procainamide. An exception Polymorphic Ventricular Tachycardia and Torsades
is rare, repetitive, idiopathic monomorphic VT, for which de Pointes
verapamil and adenosine are effective. Specific man- Polymorphic ventricular tachycardia (PMVT) in the
agement should probably not be provided for chronic absence of QT interval prolongation is PMVT and that
PVB and NSVT in patients with structural heart dis- with QT interval prolongation is torsades de pointes
ease, unless they increase in frequency or duration, (TdP). PMVT and TdP are characterized by continu-
are associated with circulatory compromise, or initiate ously changing, wide QRS complexes in any single
sustained dysrhythmias. Finally, the occurrence of ECG lead. The rate is often 100–200 beats/min, and
frequent VES or NSVT in patients not known to have prognosis is more ominous compared with SMVT. Al-
cardiac disease should alert anesthesiologists to occult though PMVT or TdP faster than 200 beats/min can be
disease, myocardial ischemia, imposed physiologic associated with hemodynamic collapse and degenera-
imbalance, or drug toxicity. tion into VF, the majority of episodes terminate spon-
taneously. Initial management for PMVT and SMVT
Sustained monomorphic ventricular tachycardia
are similar. Because PMVT often occurs in association
With sustained monomorphic VT (SMVT), uniform, with coronary disease, indicated management for this
widened QRS complexes (longer than 0.12 s) occur at is necessary (e.g., nitroglycerine, beta‐blockers, cir-
rates between 100 and 250 beats/rain for more than culatory assist devices, acute revascularization, and so
30s. SMVTs slower than 100 and faster than 250 beats/ on). However, if it is uncertain whether the patient has
min are accelerated idioventricular rhythm and ventricu- QT interval prolongation, then MgSO4 should be tried.
lar flutter, respectively. At least 90% of patients with If PMVT is associated with bradycardia, isoproterenol
SMVT have coronary artery disease with severe left (not with ischemic heart disease) or temporary pacing
ventricular dysfunction caused by a previous infarction. should be considered.
Acute ischemia, which often causes polymorphic VT Torsades de pointes can occur with acquired or
or VF, seldom produces SMVT. SMVT usually occurs congenital QT interval prolongation and management
late after infarction (more than 48–96 h) and is more differs. With acquired QT prolongation (bradycardia‐
likely a result of reentry. Aside from SMVT with chronic or pause‐dependent TdP), temporary pacing or iso-
coronary disease, other associations include dilated, proterenol (not with ischemic heart disease) to increase
hypertrophic, and infiltrative cardiomyopathies. the heart rate to 100–120 beats/min is part of acute
Initial management of SMVT depends on the rate management. In addition, causes for QT interval pro-
and duration of tachycardia, tolerance, and the extent of longation should be removed. MgSO4 is very effective in
underlying heart or other major organ system disease. suppressing pause‐dependent TdP. Antidysrhythmic
Identifiable imbalance should be managed. For patients drugs that do not increase the QT interval (class IB,
not in danger of imminent circulatory collapse, treatment bretylium) are used in refractory cases.
is started with lidocaine. If this is unsuccessful, some For TdP with congenital QT interval prolonga-
prefer DC cardioversion to bretylium or procainamide tion (adrenergic‐dependent TdP), beta‐blockers

and antidysrhythmic drugs that do not prolong the QT tomic or functional impairment. AV heart block (AVHB)
interval are used for initial and preventive therapy. Left is diagnosed when: 1) supra‐ventricular impulses
cervicothoracic sympathectomy is considered for pa- are conducted to the ventricles with delay (1st degree
tients whose symptoms are not controlled with beta- AVHB, PR greater than 0.21 s in adults or 0.18 s in
blockers. Antidysrhythmic drugs that prolong the QT children); 2) some but not all impulses are conducted
interval are contraindicated. If bradycardia precludes (2nd degree AVHB); or 3) no impulses are conducted
management with beta‐blockers, then temporary pac- (complete or 3rd degree AVHB). Second degree AVHB
ing may be required. Finally, because gene mutations is subdivided as type I (Wenckebach) and type II (Mo-
affecting inactivation of Na+ and K+ currents have been bitz) block. With type I or II block, respectively, there
linked to congenital QT prolongation, future therapy is progressive or no PR interval prolongation before
(e.g., K+ channel openers pinacidil and nicorandil) may dropped beats.
target these defects (8).
Fascicular block is block of the left anterior or
Ventricular flutter and fibrillation posterior fascicles (LAF, LPF) of the left bundle branch
Ventricular fibrillation (VF) is the most common (LBB) or the right bundle branch (RBB). Bifascicular
cause of sudden cardiac death. Up to 75% of victims heart block is block of any two of these fascicles. LBB
have coronary disease, and VF commonly develops block or RBB with LAF block are by far most common
after VT. The distinction between ventricular fibrillation types of bifascicular block. Although complete heart
and flutter (collectively, VF) is moot because both are block is often preceded by bifascicular block, progres-
incompatible with life, and management is the same. sion to complete heart block is not common.
P and T waves are absent in the surface ECG leads. By far the most common cause for acquired
Fibrillatory waveform amplitude is coarse at the onset chronic AVHB is idiopathic, progressive fibrosis of
of fibrillation and becomes fine as the VF persists. Fine the conducting system (Lev’s or Lenegre’s disease).
fibrillation identifies patients with worse survival rates Although acute myocardial infarction is an important
and may be misdiagnosed as asystole. cause of transient AV heart block, chronic coronary dis-
The only effective management for VF is defibril- ease infrequently produces persistent AV heart block.
lation with transthoracic shocks of 200–360 J delivered Volatile anesthetics may produce transient high‐grade
as soon as possible after presumptive diagnosis of AV block with CCB or amiodarone (9). Also, although
VF. Time should not be wasted administering drugs beta‐blockers depress AV node conduction, this ac-
to improve defibrillation success. Lidocaine, brety- tion highly depends on prevailing adrenergic tone. The
lium, procainamide, and amiodarone are used only potential for additive effects appears greatest with en-
to prevent recurrences of VF. A precordial thump is flurane and halothane compared with isoflurane (data
occasionally effective in terminating VF, but should for desflurane and sevoflurane are not available). The
be attempted only if a defibrillator is not available im- American College of Cardiology and American Heart
mediately because chest thumps may convert some Association Joint Task Force Committee on pacemaker
VT to VF. Initial success with defibrillation depends on implantation has published guidelines for permanent
the duration of VF. If present for only a few seconds to pacing in adults and children and temporary pacing in
minutes and if fibrillatory waves are coarse, initial suc- those with acute myocardial infarction(10). Emphasis is
cess is high. Conversely, with continued VF and fine placed on concurrence of symptoms with bradycardia
fibrillatory waves, defibrillation is more difficult. Also, if as a result of heart block or sinus node dysfunction,
VF continues for more than 4 min, there may be irre- especially in children. As for temporary perioperative
versible damage to the brain and other vital organs. pacing, pacing is indicated whenever bradycardia
caused by heart block threatens vital organ perfu-
Heart block
sion. Temporary pacing should also be considered
Atrioventricular (AV) heart block is a temporary or for bradycardia‐dependent tachydysrhythmias (e.g.,
permanent conduction disturbance resulting from ana- torsades de pointes). Finally, stand‐by ventricular

pacing should be available for patients with LBB block rhythm: feasibility as prophylaxis in 200 anesthetized
who require a pulmonary artery catheter for periopera- adults and hemodynamic effects of treatment. J Car-
tive monitoring. diothorac Vasc Anesth, 1993. 7(4): p. 436-41.
Summary 3. Atlee, J.L., Perioperative Cardiac Dysrhythmias: Diag-

nosis and Management. Anesthesiology, 1997. 86(6):
Cardiac dysrhythmias are common during anes-
p. 1397-1424.
thesia and surgery and occur in patients with structural
heart disease or normal hearts. The inciting or ag- 4. Waldo, A.L., et al., Temporary cardiac pacing: applica-
gravating factor is often physiologic imbalance unique tions and techniques in the treatment of cardiac arrhyth-
to perioperative settings (e.g., anesthetic or adjuvant mias. Prog Cardiovasc Dis, 1981. 23(6): p. 451-74.
drugs, adrenergic stress, acid‐base or electrolyte 5. Pattison, C.Z., et al., Transesophageal indirect atrial
imbalance, hypoxia, hypercapnia). If so, it is important pacing for drug-resistant sinus bradycardia. Anesthe-
to correct or remove such imbalance. Not only may this siology, 1991. 74(6): p. 1141-4.
be sufficient therapy, but it also will enhance indicated
specific treatment with drugs or devices. 6. Nattel, S., Newer developments in the management
of atrial fibrillation. Am Heart J, 1995. 130(5): p. 1094-
There are important limitations to treatment with 106.
anti‐dysrhythmic drugs. Among these is prodysrhyth-
mia, whereby antidysrhythmics may paradoxically 7. Kerin, N.Z., K. Faitel, and M. Naini, The efficacy of
aggravate dysrhythmias. Others are adverse drug intravenous amiodarone for the conversion of chronic
interactions, troublesome side effects, and cardiovas- atrial fibrillation. Amiodarone vs quinidine for conversion
cular depression. Therefore, to reduce complications of atrial fibrillation. Arch Intern Med, 1996. 156(1): p.
with treatment, the Sicilian Gambit’s pathophysiologic 49-53.
compared with more empiric approaches to drug selec- 8. Moss, A.J., et al., ECG T-wave patterns in genetically
tion has been stressed. With the Gambit’s approach, distinct forms of the hereditary long QT syndrome.
drugs are targeted at specific, vulnerable parameters Circulation, 1995. 92(10): p. 2929-34.
affecting the genesis of dysrhythmias (e.g., beta-
9. Atlee, J.L., 3rd, et al., Conscious state comparisons of
receptor, L‐type Ca2+ channels, Na+ and K+ currents).
the effects of the inhalation anesthetics and diltiazem,
Finally, although cardiac pacing is useful for prevention
nifedipine, or verapamil on specialized atrioventricular
and management, current technology is too invasive
conduction times in spontaneously beating dog hearts.
and costly for routine use. However, expected improve-
Anesthesiology, 1988. 68(4): p. 519-28.
ments with noninvasive technology will make pacing
increasingly attractive as a therapeutic modality. 10. Epstein, A.E., et al., ACC/AHA/HRS 2008 Guidelines for
Device-Based Therapy of Cardiac Rhythm Abnormali-
References
ties: A Report of the American College of Cardiology/
1. Forrest, J.B., et al., Multicenter study of general an- American Heart Association Task Force on Practice
esthesia. II. Results. Anesthesiology, 1990. 72(2): p. Guidelines (Writing Committee to Revise the ACC/
262-8. AHA/NASPE 2002 Guideline Update for Implantation
2. Atlee, J.L., 3rd, et al., Transesophageal atrial pacing of Cardiac Pacemakers and Antiarrhythmia Devices)
for intraoperative sinus bradycardia or AV junctional Developed in Collaboration With the American Asso-
ciation for Thoracic Surgery and Society of Thoracic
Surgeons. J Am Coll Cardiol, 2008. 51(21): p. e1-62.

PG DEBATE


CASE DISCUSSIONS


Hydrocephalus for Ventriculoperitoneal shunt N.Krishnan
repair 283 Aruna Subash
01 HYDROCEPHALUS FOR VENTRICULOPERI-

TONEAL SHUNT REPAIR
Additional Professor N.Krishnan
Govt Stanley Medical College, Aruna Subash
Chennai.
1. Describe the normal CSF circulation path- volume of the cranial vault is fixed once the su-
way? tures of the skull have become fused, by 2 years
of age. However, in infants even though the
Pathway: lateral ventricles- foramen of Monro-
volume of the vault can expand if the increase in
third ventricle- aqueduct of Sylvius - fourth
intracranial contents occurs gradually, such as in
ventricle- foramina of Magendie and Luschka
congenital hydrocephalus, this accommodation
- subarachnoid space over brain and spinal
has a maximum limit which once exceeded will
cord - reabsorption into venous sinus blood via
lead to an increase in ICP.
arachnoid granulations.
Brain tissue (80%) the largest component of the
2. What are the causes of hydrocephalus?
cranial contents may be pathologically enlarged
Hydrocephalus is the enlargement of the ventri- by the presence of a space occupying lesion
cles from increased production of CSF, decreased which is of insidious onset may lead to a gradual
absorption by the arachnoid villi or obstruction of increase in ICP.
the CSF pathways. Hydrocephalus is classified
Cerebral blood flow (CBF) (10%)affects cerebral
as communicating (non obstructive) or non com-
blood volume (CBV), intracranial volume, and, in
municating (obstructive). The classical distinction
turn, intracranial pressure (ICP). Cerebral blood
between obstructive and communicating hydro-
flow is higher in children compared to adults (100
cephalus is less useful clinically as the cause of
vs 50 ml/100g/min). It is coupled to the metabolic
reduced absorption of CSF in communicating
demands of the normal brain and regulated via
hydrocephalus is usually functional obstruction
oxygen requirement, PaCO2 and intracerebral
at the arachnoid villi (e.g. by blood or protein).
acidosis.
Surgical treatment for hydrocephalus involves
Auto regulation allows for a relatively constant
insertion of a drainage system to shunt CSF from
blood flow across a wide range of arterial pres-
the brain to another site in the body. Most children
sures which can be as low as 40 mmHg in small
with hydrocephalus will have some degree of
children. The “margin of safety” is narrower as the
intracranial hypertension. In patients with severe
infant is less well able to compensate for acute
intracranial hypertension, it may be necessary
hypo or hypertension.
for the surgeon to tap the shunt to remove some
of the CSF. Prevention of any further increase in Response to hyperventilation (low PaCO2) in
intracranial contents is vital as this increase may infants may be brisk, but with a risk of inducing
precipitate herniation. Rapid removal of CSF can cerebral ischemia with extremely low PaCO2 (<
also be a problem causing ventricular arrhyth- 20 mmHg).Therefore hyperventilation should only
mias, epidural or subdural hemorrhage. be used as a short term measure when ICP is
dangerously high, prior to more definitive treat-
2. What are the components in head that causes
ment. Hypertension in infants may present risk
intracranial pressure ?
of intracranial hemorrhage.
The cranial contents consist of brain tissue (80%),
All inhalational anesthetics increase CBF and CBV
blood (10%) and cerebrospinal fluid (10%). The
by producing vasodilatation

Cerebrospinal fluid (CSF) (10%) is continu- Symptoms and signs of increased ICP : vom-
ously produced by the choroid plexus, and after iting, poor feeding, inappropriate sleepiness,
circulating through the ventricles is absorbed at irritability, drowsiness, fullness or increased ten-
the arachnoid villi. The arachnoid villi act as one sion of the fontanelles , metopic, coronal, sagittal,
way valves between the subarachnoid space and lambdoid suture splaying, increasing head
and the dural sinuses. CSF acts as a cushion circumference, and limited up-gaze or forced
that protects the brain from shocks and supports down-gaze (sun setting sign). Infants and young
the venous sinuses (primarily the superior sagit- children often do not exhibit the traditional signs
tal sinus, opening when CSF pressure exceeds of intracranial hypertension such as Cushing’s
venous pressure). It also plays an important role response hypertension and bradycardia, dilation
in the homeostasis and metabolism of the central of the pupils, and papilledema. If present, these
nervous system. In children the rate of produc- signal severe progression with poor outcomes.
tion of CSF is 0.2-0.4 ml/min with around 250 ml
Long term increases in ICP can impair neurologi-
produced and absorbed per day and at any given
cal development, whilst in the acute setting, high
time around 70 ml is present in the head. Any
ICP can cause distortion of the cerebral contents
interruption to normal flow, increased production
through the foramen magnum - “coning” – leading
or decreased re-absorption of CSF can manifest
to coma, respiratory arrest and death.
itself as hydrocephalus which may lead to raised
ICP. 6. What are the various treatment methods avail-
able to decrease intracranial pressure?
4. Define cerebral perfusion pressure ?
To decrease cerebral blood volume
Cerebral perfusion pressure is defined as the
difference between the mean arterial pressure Hyperventilation
(MAP) and the sum of intracranial pressure and 30° head elevation in neutral position
the central venous pressure (CVP).
Administration of barbiturates
We can increase CPP by either
Administration of paralytic agents
• By increasing MAP (with fluids, vasoconstrictors
Administration of sedative agents
or inotropes) .
Prevention of hyperthermia
• By reducing ICP (hyperventilation, mannitol, seda-
tion and analgesia). To decrease brain bulk and cerebrospinal fluid
(CSF)
• By reducing CVP (head up position, head midline,
avoiding obstruction of venous drainage of neck Osmotic diuretic (mannitol)
with central lines or tight endotracheal tapes).
Loop diuretic (furosemide)
ICP- normal value -The normal range of ICP in
Glucocorticoid steroids (dexamethasone)
neonates is 2-4 mmHg (7-15 mmHg in adults).
At ICP > 20mmHg focal ischemia occurs. At ICP Acetazolamide to decrease CSF production
>50 mmHg global ischemia occurs. Intraventricular drainage of CSF
5. How do you diagnose a raised ICP in chil- Surgical resection of a selected cerebral lobe or
dren? brain tumor
The infant skull is not fully ossified and is more To decrease intracranial volume
compliant (viscoelastic) than the adult skull and
has the ability to expand at the open fontanelles Surgical decompression of adjacent brain (ie,
and nonfused sutures. lobectomy)

Extensive decompressive craniectomy and dural of raised intracranial pressure, past medical his-
expansion to allow for cerebral swelling. tory, current medication (e.g. anticonvulsants,
acetazolamide,furosemide), allergies and last oral
7. Explain various causes for hydrocephalus?
intake. Examination should include assessment
(1) Congenital of the airway, cardio respiratory and neurologi-
Aqueductal stenosis, cal systems, which in cases of raised ICP may
demonstrate reduced level of consciousness and
Myelomeningocele,
therefore increased risk of pulmonary aspiration.
Arnold-Chiari malformation, Volume status should be determined as prolonged
vomiting and dehydration may necessitate intra-
Spina bifida,
venous fluid preoperatively.
Dandy-Walker syndrome,
Examine to the possibility of comorbidities
Mucopolysaccharidoses (with obliteration of with anesthetic implications like
the subarachnoid space),
Congenital heart disease can produce hypoxia
Achondroplasia (with occipital bone over- and cardiovascular collapse
growth).
H/o prematuriy and postop apnea
(2) Acquired
Recurrent respiratory tract infection and its laryngo
IVH and bronchospasm
Space-occupying lesions, H/o anticonvulsant drugs and its effect on hepatic
Infections (abscess and meningitis). drug metabolism
8. What are the surgical management of hydro- Hyperkalemia with suxamethonium,if any dener-
cephalus? vation injury
The shunt provides a route for the CSF to drain Difficult intubation and ventilation due to cranio-
and decreases ICP. The proximal end is placed facial abnormality
in the ventricle and the distal end at a site where Problems due to hypothalamic and pituitary prob-
the CSF can be absorbed (most commonly peri- lems.
toneum but atria and pleura are also used).
Problems of malignant hyperthermia, respiratory
1. Ventriculoperitoneal shunt and cardiovascular failure due to neurological
2. ventriculoatrial shunt disease.
3. Ventriculopleural shunt 10. What are the investigations you will order?
4. ventriculojugular shunt Blood results should be reviewed to ascertain

the level of hemoglobin and clotting function so
5. ventriculostomy that appropriate blood products can be ordered
Ventriculoperitoneal shunting: This procedure as indicated. Urea and electrolytes should be
is by far the most common procedure for CSF checked if medical problems or drug treatment
diversion. The abdomen should be able to absorb suggest that they may be abnormal and require
the excess spinal fluid. attention perioperatively. Neuroimaging studies
(ie, head displacement CT, ultrasonography, or
9. How will you assess a baby coming for VP
MRI) are critical to facilitate proper treatment.
Shunt?
The preoperative visit is an essential component
of any anesthetic technique. History suggesting
11. How will you manage a sudden neurologic not be used as it can increase ICP. Muscle relax-
detoriation? ation can be achieved with the use of a neuro-
muscular blocking agent (NMB). Suxamethonium
Sudden neurologic deterioration in the pediatric
can be used if the risk of aspiration outweighs
patient must be treated quickly with emergency
the problems of transient increases in ICP, hy-
endotracheal intubation, muscle relaxation, hyper-
perkalemia if associate with denervation injuries.
ventilation with ETCO2 monitoring, administration
Otherwise non-depolarising NMB are preferable.
of cerebral protective drugs (e.g., barbiturates)
Patients on chronic anticonvulsant therapy will
diuretics (e.g., mannitol, furosemide) until emer-
require larger doses of muscle relaxants and nar-
gency surgical reduction of the ICP is achieved.
cotics because of induced enzymatic metabolism
Control of the ICP is sometimes accomplished by
of these agents. Child should be hyperventilated
a direct needle puncture of the lateral ventricle
to reduce PaCO2 level. Hypercarbia should be
and aspiration of CSF.
avoided as it causes cerebral vasodilation and
12. Comment on the premedication you will give may worsen raised ICP especially in combination
to a patient coming for VP shunt? with laryngoscopy and airway manipulation.
Sedative premedication should be avoided in pa- 13. Comment on the position you will choose to
tients suspected of increase in ICP. These drugs intubate for this patient?
might further embarrass respiration, because
Congenital hydrocephalus may have distorted the
hypercarbia and cerebral vasodilatation, and lead
anatomy of the skull which can make manage-
to tonsillar herniation Preoperative sedation may
ment of the airway more difficult. Often a pillow
be indicated as intense crying or screaming or
placed under the body of the neonate can facilitate
fighting can cause significant elevations in ICP.
laryngoscopy. The lumbar menigocoele should
Sedation with oral midazolam is preferable as less
be protected with a ring to avoid undue raise in
respiratory depression or change in PaCO2 has
intracranial pressure and possibility of rupture.
reported shown with oral midazolam premedica-
tion in children .Other medications such as opi- The airway should be secured by intubation of
oids and thiopental cause respiratory depression the trachea with an appropriate sized tracheal
and should be used with caution in patients with tube. This should be a reinforced (armoured)
elevated ICP. Ketamine should be avoided as tube if available but a standard tube can be used
it increases both cerebral blood flow (CBF) and providing this information is communicated to the
cerebral metabolic rate and will elevate ICP. surgeon, as the tube will be more likely to kink dur-
ing positioning. The tube should be firmly secured
13. How will you induce this patient?
with waterproof tape and dressing and the eyes
The patient’s neurological status and coexisting should be padded and taped.
medical issues will guide the choice of anesthetic
14. How will you position this patient for surgery
induction.
and what problems you expect?
Intravenous induction allows for rapid control of
For ventriculoperitoneal shunt surgery the position
the airway in emergency situations if the patient is
is supine. The head is turned to the contralateral
not fasted and if no difficulties with the airway have
side of the site of insertion of the shunt. Neck
been anticipated. This may be achieved using a
flexion may result in migration of the endotracheal
suitable induction agent in a carefully titrated sleep
tube to the main stem bronchus. Neck flexion
dose (proprofol 2-4 mg/kg, thiopentone 3-5 mg/
may occlude the jugular vein impeding venous
kg). Hypotension should be avoided because of
drainage and increasing intracranial volume and
the risk of decreasing cerebral perfusion pressure
pressure. Extra care should be exercised with
(CPP) in the face of raised ICP. Ketamine should
securing the endotracheal tube in this position.

A roll of towel can be placed under the shoulders 16. Explain about intraoperative maintenance of
to facilitate a straight line from the ear/neck to the anesthesia?
abdomen for tunnelling of the shunt. The eyes
Anesthesia can be maintained with a volatile
should be protected from drying and injury.
agent and a mixture of oxygen and air. All volatile
15. What are the monitors you will need for doing anesthetics can cause cerebral vasodilation and
this case? increase ICP. Isoflurane and sevoflurane appear
to have minimal effects on CBF and cerebrovas-
Routine monitors:
cular reactivity to CO2 in concentrations of 0.5-1.5
The precordial stethoscope minimum alveolar concentrations. The aim is to
Electrocardiogram maintain CPP until the raised ICP is relieved by
positioning of the VP shunt. To do this hypoten-
Pulse oximeter,
sion should be avoided and minute ventilation
EtCO2 controlled to maintain normocarbia (end tidal CO2
4-4.5 kPa) to optimise CPP and avoid increases
Noninvasive blood pressure
in ICP. Positive end-expiratory pressure (PEEP)
Esophageal stethoscope should be minimised to avoid venous congestion
Temperature probe in the head but may be used if there are difficulties
in maintaining oxygenation.The most stimulating
A peripheral nerve stimulator to monitor the de- parts of the surgery include the initial incision and
gree of neuromuscular blockade. tunnelling under the skin. A short acting opioid,
Special Monitors: such as fentanyl (1-3 mcg/kg) or remifentanil (1
mcg/kg), or increased depth of anesthesia, can
• Monitoring for Venous air embolism (VAE)
be used to attenuate the increase in heart rate
may occur during craniotomy in infants because
and ICP.
of the head position and surgical approach. The
head of a small child is large in relation to the 17. Which anesthetic agents decrease brain
rest of the body, causing it to lie above the heart, CMRO2?
even in the supine position. In addition, the head Propofol, etomidate, thiopental, volatile anesthet-
of the bed is often elevated to facilitate drainage ics and to a lesser extent benzodiazepines, lido-
of blood and CSF during operation. Pressure caine and nitrous oxide decrease brain CMRO2.
within the superior sagittal sinus decreases as the Opioids do not decrease CMRO2.
head is elevated, increasing the likelihood of VAE.
Patients who have a patent ductus arteriosus or 18. How does mannitol influence intracranial pres-
foramen ovale are also at risk for paradoxical air sure?
embolism through these defects. Consequently, Intracranial volume is reduced by the increased
precordial doppler ultrasonography is used in osmolality caused by mannitol in the blood pulling
conjunction with ETCO2 sampling and direct mea- water out of the brain compartment. Mannitol is
surement of arterial blood pressure for detecting also a weak vasodilator and causes a transient
and assessing treatment of VAE. increase in cerebral blood volume. The overall
• ICP monitoring facilitates the achievement of affect of mannitol is to decrease ICP.
preset physiologic and biochemical goals and the 19. What effect does PaCO2 have on intracranial
assessment of patients’ response to therapy. pressure?
PaCO 2 causes cerebral vasodilation and in-
creases cerebral blood flow by 2-4% per mm Hg

increase in PaCO2 within the range of 20 and 80 In patients with existing intracranial hypertension,
mm Hg. The increased CBF leads to increased drugs may be used to reduce ICP like furosemide,
intracranial blood volume resulting in an increase a loop diuretic, is often used to induce diuresis
in ICP. and decrease cerebrospinal fluid production.
Hyperosmolar therapy with mannitol or hypertonic
20. Explain about temperature maintenance in
saline (3%) is often used.
these patients?
Blood and blood component therapy use is guided
Temperature control is an important consideration
by the degree of blood loss, starting hematocrit
in the management. Mild to moderate hypothermia
level, and blood coagulation studies.
may be neuroprotective and may be therapeutic
in the presence of ischemia or hypoxia. In infants, 22. Explain about extubation in this child?
reduced body temperature will have markedly
The goals for emergence include prompt awaken-
increased oxygen consumption, decreased drug
ing to aid early assessment of neurologic func-
metabolism, increased lactate production and
tion, hemodynamic stability, minimal coughing
metabolic acidosis, peripheral vasoconstriction,
or straining on the endotracheal tube to avoid
and shift of the oxy-hemoglobin dissociation curve
intracranial hypertension and bleeding. Patients
to the left, prolonged emergence from anesthesia,
may receive fentanyl before emergence.
coagulopathy, immunodeficiency and derange-
ment in serum glucose metabolism. Severe At the end of the procedure neuromuscular block-
hypothermia may result in cardiac arrhythmias. ade can be antagonized using neostigmine (50
mcg/kg) combined with an anticholinergic (e.g.
21. Explain about your fluid management?
atropine 25 mcg/kg).
The goal of fluid management is maintenance of
Most patients can be extubated once awake,
cerebral perfusion, which usually translates into
avoiding hypercarbia, and with a technique which
maintenance of isovolemia, iso-osmolarity, and
minimizes the risk of aspiration - lateral posi-
iso-oncotic blood volume.
tion.
Fluid restriction and diuretic therapy may lead to
Alternatively extubate the trachea when the patient
hemodynamic instability and even cardiovascu-
is still deeply anesthetized if there is no contrain-
lar collapse if sudden blood loss occurs during
dication (e.g., intraoperative catastrophe, loss of
surgery. Therefore, normovolemia should be
airway reflexes, poor preoperative condition).
maintained through the procedure. Normal saline
is commonly used as the maintenance fluid during If the patient’s awakening is delayed and no
neurosurgery because it is mildly hyperosmolar anesthetic cause can be determined, the pres-
(308 mOsm/kg), and it theoretically attenuates ence of a neurologic issue can be revealed by a
brain edema. However, rapid infusion of normal computed tomographic (CT) scan before tracheal
saline (30 mL/kg/h) is associated with hyperchlo- extubation.
remic acidosis. 23. Explain about your plan for post operative
Hyperglycaemia is associated with worse brain care?
injury after ischemia; therefore, dextrose admin- Post-operative analgesia can be provided by
istration is not used routinely. Infants, particularly a combination of infiltration of local anesthetic
those who are pre-term, are at higher risk for such as bupivicaine 0.25% (0.5-0.75 ml/kg) and
hypoglycaemia. This group should have blood paracetamol (15 mg/kg) either intravenous or per
glucose measurements taken during long proce- rectum. High doses of long acting opioids should
dures and dextrose administered if indicated. be avoided because of potential detrimental ef-
fects on conscious level.

The patient should be monitored in a suitable REFERENCES:

environment by those familiar with paediatric
1. Smith: anesthesia for infants & children
neurosurgical cases and able to carry out regular
neurological observations. Respiratory dysfunc- 2. Cote: a practise of anesthesia for infants & children
tion may occur in the postoperative period. There 3. Paediatric neuroanesthesia: anesthesiology clin n am
may also be airway obstruction secondary to 20 (2002) 389– 404
either edema or cranial nerve injury and apnea
4. Current management of medical neurology
from injury to the respiratory control center in the
brain stem. 5. Anesthesia for neurosurgery in infants and children
jayant k. Deshpande, m.d.

Scoliosis Correction 290 Balabhaskar
01 SCOLIOSIS CORRECTION
Professor Balabhaskar
Scoliosis Correction Effect of scoliosis on respiratory and cardiovas-

cular system
A 20 year female was diagnosed to have deformity
in the back since birth which is progressively increasing Scoliosis of the spine and the rib deformity are re-
causing limitation of routine activity. She has dyspnea sponsible for the adverse effects on respiratory and
on mild to moderate exertion. On evaluation, she is thin cardiovascular systems(1) (fig1).
built, body weight is 35 kg, and has thoracic scoliosis
with the concavity facing the left side. The heart rate is
100/minute, BP of 100/70mm of Hg. The breath holding
time is less than 10 seconds, RR-22/min at rest with
normal vesicular breath sounds bilaterally. The CVS
examination revealed a soft systolic murmur in the
pulmonary area.
The patient is planned for scoliosis correction with
instrumentation and osteotomy.
Investigations
Hb-10gms%
Chest X-ray-thoracic scoliosis with Cobb’s angle of
60o Fig (1) Scoliosis and Cobb Angle
Echocardiogram shows normal LV function with moder- Relevant details available in this case:
ate pulmonary artery hypertension.
- Idiopathic thoracic scoliosis, Cobb angle is 60°
Pulmonary function test shows 40% of predicted vital
- Progressive over 20 years since birth
capacity and shows restricted type of defect.
- Dyspnea on mild to moderate exertion, heart rate
Discussion
100/minute, BP 100/70 mm of Hg
Effect of scoliosis on respiratory and cardiovascular
- Breath holding time <10 seconds, RR-22/min at
system
rest with normal vesicular breath sounds bilater-
Concerns in prone position ally
Planning for blood conservation strategies - Soft systolic murmur in the pulmonary area
Spinal cord blood supply and monitors to assess spinal - PFT : Restrictive Pattern, VC 40% of predicted
cord integrity
- Echo: moderate pulmonary artery hypertension.
Wake up test-its role and complications
Scoliosis and respiratory system
Post op ventilator strategies and pain relief
A restrictive pattern of lung disease results in
scoliosis with reduction in chest volume.
- The reduced lung compliance and restrictive pat-

tern are inversely related to the angle of curvature Sabrazes’s breath holding test (Voluntary Apnoeic
(Cobb Angle). Angles more than 60°- 65° are as- Pause) (Jean Sabrazes,1902) is the time for which a
sociated with significant respiratory manifestations. person can hold his/her breath, after a deep inspira-
tion. It reflects the cardio-pulmonary reserve of the
- Intercostal muscles act at a mechanical disad-
patient. Values are - Normal: 25-30 Seconds (VC of
vantage because of the chest cage deformity
atleast 3.5 l (M), 3.0 l (F)),< 20 Secs : Decreased CP
and there is reduction in total lung capacity and
reserve, ≤ 10-15 secs : VC is 1500 ml or less. Breath
vital capacity (VC is greatly reduced). Reduction
holding in the present case is < 10 secs. and the VC
in vital capacity to less than 40% predicts need
is 40% predicted. (Other tests that can be performed
for post-operative ventilation.
are Schneider’s Match blowing test, expiratory time on
- Total lung capacity, functional residual capac- auscultation over trachea, De Bono’s Whistle, Cough
ity (FRC), inspiratory capacity, and expiratory Test, Hand held spirometer / bed side Peak flow meter,
reserve volume are all decreased. etc.) PFTs show a restrictive pattern in the present
- Unless there is coexisting obstructive airway dis- case, discussed above.
ease, the ratio of the forced expiratory volume in Scoliosis and cardiovascular system(2,3)
1 second to the forced vital capacity (FEV1/FVC)
There is increase in pulmonary vascular resistance
is normal.
due to effects of scoliosis, by several mechanisms.
- Inspiratory force falls to 70% of normal values due
1. Compression of the lungs by rib cage impairs
to impaired inspiratory muscle contraction due to
normal development of pulmonary vascular bed
chest deformity.
and causes alveolar collapse. Blood is forced
- Small tidal volume and tachypnea reduce the work through high resistance extra-alveolar vessels.
of breathing but increase dead space ventilation
2. Prolonged hypoxia with hypoventilation and V-Q
and alveolar hypoventilation.
mismatch precipitates irreversible vasoconstric-
- Hypoxemia results because of ventilation-perfu- tion and pulmonary hypertension.
sion abnormalities. Reduced oxygen tension with
3. Studies of asymptomatic adolescents with idio-
a normal carbon dioxide tension is common but
pathic scoliosis indicate that cardiopulmonary
as the disease progresses, ventilation-perfusion
abnormalities may develop parallel to, rather than
abnormalities worsen with increased ventilator
in response to structural changes.
requirements and eventual respiratory failure.
Normal pulmonary vascular resistance is 50-140
- Hypoxia, hypercapnea and pulmonary vasocon-
dynes/s/cm5 and PHT is associated with values more
striction result in irreversible pulmonary vascular
than 240 dynes/s/cm5(also expressed as Wood units-
changes and pulmonary hypertension.
divide the above by 80). Pulmonary hypertension is a
In neuromuscular associated scoliosis, lesser de- hemodynamic and pathophysiological condition defined
grees (<30°) of angulation are associated with severe as an increase in mean pulmonary arterial pressure
impairment. If marked scoliosis is present before 8 (PAP) ≥25 mmHg at rest as assessed by right heart
years of age, alveolar development will be arrested. catheterization (normal mean PAP at rest-14±3 mmHg,
SCOLIOSIS⇒Reduced lung volumes, V-Q Abnor- with an upper limit of normal of 20 mmHg) (3).The defi-
malities, Reduced chest wall compliance, Increased nition of PH on exercise as a mean PAP >30 mmHg
pulmonary vascular resistance ⇒ HYPOXEMIA as assessed by right heart catheterization is not sup-
ported by published data. Clinically, patient goes into
HYPOXEMIA⇒ Increased ventilatory requirements,
gradual increases in breathlessness and hypoxia due
Compensation, Failed compensation and progression
to increased pulmonary vascular resistance. Respira-
⇒ Hypoxia, Hypercarbia ⇒RESPIRATORY FAILURE,
tory infections, bacterial or viral promote pulmonary
DEATH

congestion and precipitate symptoms. Pulmonary hy- Problems of positioning may relate to anatomical
pertension (PH) & Right heart enlargement (RVH) are effects related to head and neck, eyes, upper limbs,
followed by cardiac failure. Initial respiratory findings in ears and physiological effects (abdomen, air embo-
scoliosis include a loud pulmonic second sound (P2), lism).
indicating elevated pulmonary artery pressures. P2 is
Head and neck : Excessive flexion or extension
louder than the aortic second sound (A2) in the pul-
should be avoided; it should be possible to inspect
monic area, which remains louder as the stethoscope
face and eyes easily, as the position may be altered
is moved down toward the apex of the heart. Increased
during surgery. Care is necessary when cervical spine
pulmonary pressures result in systolic murmer at the
abnormalities accompany scoliosis in some subtypes.
pulmonary area. An audible right ventricular fourth heart
Endotracheal tube kinking or dislodgement is a risk.
sound (S4) and a tricuspid regurgitant murmur may be
heard, becoming more prominent as the right ventricle Eyes : Corneal abrasion may occur; they should be
dilates. If the pulmonary valve ring also dilates, a Gra- taped & closed securely.Application of lubricants may
ham Steele pulmonary insufficiency murmur may result. be useful. Supraorbital nerve injury due to pressure
In patients with advanced disease, a right ventricular effect should be avoided. Pressure on the eyes may
third heart sound (S3) can be heard and is associated cause thrombosis of the central retinal artery producing
with a poor prognosis. Advanced right heart failure is loss of vision or blindness. Unilateral eye blindness is
associated with jugular venous distention, oedema and reported with use of horseshoe-type head rest.
ascites. ECG evidences appear late and are not reliable Ears : Injury and ischemia to ear may occur and hence
(RVH, ‘p’pulmonale, RV strain pattern, dysrrhythmias). checked frequently during the procedure. Necrosis
RVH and PH are better diagnosed by echocardiography of the dependent ear cartilage may occur if pinna is
and is performed if physical findings are suspicious. doubled up on itself.
25% of patients with idiopathic scoliosis have an api-
Upper extremities: Brachial plexus may be stretched
cal systolic murmer of mitral valve prolapse (MVP);
if arms are abducted above the head beyond 90°,
echocardiography is a diagnostic tool for MVP and the
leading to brachial plexus palsy. Ample space between
identification and grading of pulmonary hypertension.
the thoracic bolster of the frame and the axilla avoids
Scoliosis is associated with increased incidence compression of axillary sheath. Ulnar nerve may be
of congenital heart diseases; coarctation and cyanotic pressed at the elbow and adequate padding must be
heart disease are more common, possibly due to a provided. Arterial or venous occlusion of the upper
common embryonic insult. There may be complex extremity is a possibility.
patterns of blood flow and residual disturbances even
Lower extremities: Peroneal and lateral femoral
after definitive repair. There is a high incidence of MVP
cutaneous nerve injury due to pressure should be
which may indicate a systemic soft tissue collagen
anticipated and adequate padding provided.
defect. Presence of CHDs with MVP necessitates use
of infective endocarditis prophylaxis. Abdomen : Compression by operating frame (Relton-
Hall frame) or misplaced padding can impair ventilation
Concerns in prone position
and increase bleeding due to increased venous pres-
Posterior spinal fusion is the most common sur- sure. Diaphragmatic excursions remain efficient and
gical technique performed with the patient positioned paravertebral venous congestion is reduced.
prone, neck slightly flexed, and arms anteriorly flexed
Venous Air Embolism (VAE) : Large amount of bone
and abducted. Chest and iliac crest are supported by
exposure with the surgical site above the level of heart
chest rolls to leave the abdomen free. If proper care is
predisposes to air embolism. Prompt diagnosis and
not taken during positioning, significant adverse effects
management can reduce mortality. Wound must be
may ensue.
flushed with saline, nitrous oxide discontinued and
vasopressors administered.

Planning for blood conservation strategies (2,4,5) (Ho+Hf) / 2 or = EBV x (HbO-Hbf) divided by
(HbO+Hbf) / 2
Relevant details available in this case:
Eg: For a 25 kg. patient with 12gm% Hb and36%
- Body weight - 35 kg
Hct, with average target Hb of 9 gm% and Hct of
- Hb - 10gms 27%:
- BP - 100/70mmof Hg Estimated blood volume (EBV) = 25x70=1750
- Cobb’s angle of 60o ml.
Blood loss during spinal instrumentation and fu- Based on the above formulae, amount withdrawn
sion occurs with decortication and is proportional to = 500 ml., which is replaced by equal amounts
number of vertebral levels decorticated and surgical of colloids or 3 times volume of crystalloids or a
time. Blood transfusions are usually needed. combination of both.
Complications associated with homologous blood In the present case (if the patient refuses ho-
transfusion, transfusion reactions, transmission of mologous blood) : 35kg patient with 10 gm% Hb,
infections, isoimmunisation, hepatitis, etc., must be if target Hb is fixed at 9 gm%,
borne in mind. Autologous transfusions avoid these EBV = 35x70 = 2450 ml, amount withdrawn =
problems. Homologous blood transfusions may be 2450 x (10-9)/(10+9)/2 = 250 ml (appr).
needed, however, in young children and those with
Replacement: 750 ml of crystalloid or 250 ml col-
overall poor status.
loid can be given.
Various strategies can be used to reduce blood loss and
Preoperative donation and isovolemic hemodilu-
to conserve the blood in the perioperative period:
tion can be carried out in the same patient as long
a. Preoperative donation: This is initiated about 4 as the starting Hb and Hct levels are in acceptable
weeks preoperatively, allowing 4-7 days between range.
donations; 4 units or more can be collected, de-
c. Intra operative blood salvage: 50% to 60% of
pending on need and patient’s hemoglobin status
the red blood cells lost can be recovered, concen-
and stored at 4°C.
trated, washed, and returned to the patient using
b. Intra operative isovolemic hemodilution: commercially available autotransfusion devices
Crystalloids can be infused before incision with (Cell Savers). Platelets and plasma are however,
a targeted hematocrit (Hct) of 25%-28% and not part of the collection.
then removing blood aseptically and storing it in
d. Induced hypotension: Moderate induced hy-
anticoagulated bags: this reduces blood viscos-
potension with normovolemic hemodilution can
ity and promotes organ perfusion. Isovolemic
bring down transfusion requirements by 50% and
hemodilution also reduces red cell loss during
shorten operating times. Mean arterial pressure
surgery. Intravascular volume is maintained by
(MAP) is lowered to 65 mm Hg using inhalational
replacing the blood with three times the volume of
agents (halothane, enflurane, isoflurane) or use of
a balanced saline solution, or an equal volume of
drugs such as trimetaphan, nitroglycerin (NTG),
colloid. Intraoperatively, the previously withdrawn
sodium nitroprusside (SNP). Halothane is arrhyth-
blood is replaced as needed.
mogenic and greater depressant of myocardium
If preoperative Hb and Hct are known, target Hb than the other agents. Since all inhalational agents
and Hct is fixed at 9-10 gm% and 25-28% respec- produce a dose dependent deterioration of SSEP
tively; amount of blood that can be drawn can be waveforms, they are of limited use in this regard.
calculated. SNP is reliable but is associated with tolerance,
Amount withdrawn = EBV x (Ho-Hf) divided by tachyphylaxis, toxicity and rebound hypertension.

NTG maintains or increases spinal cord blood flow loss.

but not as effective in maintaining the targeted
h. Pharmacologic agents: Aminocaproic acid
BP. The rebound hypertension and the reflex
(Synthetic lysine analogs) and aprotinin (poly-
tachycardia can be avoided by preadministration
peptide with serine protease inhibitor activity)
of a dose of beta blocker or ACE inhibitor.
and tranexamic acid (inhibitor of plasminogen
Spinal cord ischemia and neurologic deficits may activation) have been tried with some success.
be a risk in presence of preoperative hyperten- Recombinant factor VIIa has been reported to
sion, hypocapnoea, intraoperative MAP < 60 prevent and/or treat severe bleeding during spine
mmHg, rapid falls in BP and anaemia. surgery.
Benefits-risks must be weighed before instituting In the present case,with 10gm% and BP of
induced hypotension. 100/70 mmHg. (MAP 80 mm Hg), preoperative
collection is not a desirable option. Pre-operative
e. Patient Positioning: Keeping the abdomen free
homologous transfusion is beneficial, followed, if
avoids epidural venous engorgement and thus
necessary by intraoperative isovolemic hemodi-
bleeding. Muscle relaxants and adequate depths
lution and if facilities are available, cell salvage.
of anesthesia aid in reducing intra-abdominal
Collection from drainage bags from thoracotomy
pressure.
and use of induced hypotension to 65mmHg MAP
f. Ventilation: IPPV is maintained but PEEP is using NTG and proper positioning and ventilation
avoided to promote venous return. are other measures which can be used in the
g. Subcutaneous infiltration before skin incision: present case.
Use of adrenaline (1:500,000) can decrease blood
Spinal cord blood supply and monitors to assess spinal cord integrity
Fig 2. Spinal cord blood supply

Spinal cord blood supply and monitors to assess Blood flow is affected by arterial oxygen and carbon
spinal cord integrity dioxide tensions-hypocapnoea reduces blood flow and
hypercapnoea and hypoxia cause vasodilatation and
The spinal cord is supplied by one anterior and
increased flow.
two posterolateral arteries that run along the length
of the spinal cord and the radicular arteries that are Monitors to assess spinal cord integrity
segmental and enter the vertebral foramina, reaching
Spinal cord may be injured during the corrective
the spinal cord along with nerve roots.
surgery for scoliosis, mostly because of distraction of
Anterior spinal artery with the radicular arteries cord by instrumentation, disruption of arterial supply or
supply the anterior two thirds of the spinal cord. Anterior compression due to hematoma; direct surgical injury
spinal artery ischemia causes loss of motor function, is not common. Risk is more in severe cases (angle
pain and temperature sensation. >120°), congenital variety, kyphosis and preexisting
neuromuscular deficit. Rate of paraplegia (Complete or
Anterior spinal artery (ASA) is a single vessel
Partial) is around 0.26%, combined anterior/posterior
formed by the joining of the terminal segments of each
procedures having higher rate of spinal cord injuries
vertebral artery. It descends in the median fissure of the
compared to either anterior or posterior procedures.
cord. A series of 6 to 8 anterior radicular arteries arising
Hence, intraoperative compromise of spinal cord func-
from vertebral, thyrocervical, costocervical, intercostal,
tion needs to be detected early and reversed early.
and iliac vessels supply the ASA at various levels along
Maintenance of oxygenation & blood pressure, correc-
the length of the cord. The largest radicular artery is
tion of other precipitating factors and lastly, if there is
the radicularis magna (artery of Adamkiewicz), which
no improvement, adjustment or removal of the instru-
supplies the anterior spinal artery in the thoracolumbar
mentation has to be tried. Following are the specific
region of the cord. It arises between T9-T12 in 60%,
techniques for assessing spinal cord integrity:
T5-T8 in 14% and below L1in 26% of cases. The magna
may supply one quarter to one half of the blood supply 1. For integrity of dorsal column pathways: Soma-
to cord. tosensory evoked potentials (SSEPs) and
Blood flow is caudad, upto midcervical parts of 2. For integrity of ventral / motor pathways: The
the cord whereas it is cephalad in thoracic regions, intraoperative wake-up test and Motor evoked
presumably because the radicularis magna is the potentials (MEPs)
major source here. Wide distances between radicular
3. Electromyograms are used to monitor nerve root
arteries position creates ‘watershed’ areas which are
injury during pedicle screw placement and nerve
at risk for ischemia, especially in upper thoracic and
decompressions.
lumbar regions. One such frequently observed area is
between T4-T9. Somatosensory evoked potentials (SSEPs)
The paired posterior spinal arteries arise from The posterior columns of the spinal cord receive
posterior inferior cerebellar arteries, and descend along sensory information from the periphery and pass them
the posterolateral aspect of the cord. Between 25-40 on to the cerebral cortex. A continual assessment of
posterior radicular arteries supplement the posterior this pathway is SSEP monitoring. Repeated electrical
vessels. The posterior arteries supply only the dorsal stimuli are applied to a peripheral nerve such as poste-
columns and have widespread anastomosis. Hence, rior tibial nerve at the ankle or the median nerve at the
injury to one of them will not necessarily result in isch- wrist and the evoked response over the cerebral cortex
emia. and subcortical regions are analysed using standard
scalp EEG electrodes. SSEPs are good predictors of
Spinal cord blood flow autoregulates between
normal postoperative sensory function. The dorsal
60 to 150 mmHg mean arterial pressures. MAP below
column pathways (proprioception and vibration), per-
the lower level may result in ischemia. Autoregulation
is affected by trauma, surgery and anesthetic agents. fused by posterior spinal artery are monitored, leaving

the motor pathway supplied by anterior spinal artery MEP monitoring has potential for adverse effects,
unmonitored. including cognitive deficits, seizures, bite injuries,
intraoperative awareness, scalp burns, and cardiac
An increase in the latency (10%-15% or more),
arrhythmias. Bite block is advised during MEP monitor-
a decrease in the amplitude (>50%), or a complete
ing to prevent tongue biting and dental damage. MEP
loss of the evoked potential is considered indicative of
monitoring should be avoided in patients with active
surgical injury or ischemia until proved otherwise. As
seizures, vascular clips in the brain, and cochlear
discussed already, sensory function (and SSEPs) are
implants.
preserved because the posterior columns receive their
blood supply from the posterior spinal arteries. Hence, Wake up test - its role and complications (2,4,5)
information from SSEPs must be supplemented by ad-
The wake-up test, first described by Vauzelle
ditional tests (wake-up test or MEPs) to monitor spinal
(1973), is used to assess integrity of motor pathways
cord function during scoliosis surgery.
and is performed by bringing the patient to lighter
It is important to remember that SSEPs may be planes of anesthesia, sufficient to allow the patient to
modified by other factors as well. Cortical (not sub- follow commands. The test is performed once instru-
cortical) SSEP amplitude and latency are affected by mentation is in place or when monitoring indicates
hypercarbia, hypoxia, hypotension and hypothermia. A abnormality.
decrease in MAPs below levels of cerebral autoregula-
Patients are informed of this step preoperatively
tion and hematocrits below 15% will affect both SSEPs
and reassured that only minimal pain will be felt and
and MEPs.
that once they move their hands and feet, anesthesia
All volatile anesthetics reduce the amplitude and will be deepened.
increase the latency of cortical SSEPs in a dose de-
Surgeon should notify atleast 30 minutes in ad-
pendent manner (not subcortical).Effective SSEPs can
vance, so that bolus injections of relaxants or opioids
be obtained with 0.75% to 1% concentration (with 60%
are avoided prior to awakening. During this period,
N2O). Nitrous oxide produces a decrease in amplitude
volatile anesthetic is discontinued, allowing for gradual
in SSEPs without an increase in latency. Among the
awakening. Narcotic infusions may be continued till 5
IV agents (propofol, benzodiazepines, droperidol,
minutes before wake up. N2O is withdrawn and patient
etomidate, ketamine, barbiturates, narcotics), narcot-
ventilated by hand. (Meanwhile, wound may be covered
ics probably have the least effect on SSEPs; muscle
with wet packs to avoid VAE with spontaneous deep
relaxants have no effect on SSEPs.
ventilation). Ideally no reversal of muscle relaxants is
Motor evoked potentials (MEPs) performed, leaving patient partially paralysed but able
to make limited but detectable movements of the hands
Integrity of the anterior (motor) pathways is tested
and feet(allowing at least three twitches on train-of-four
by transosseous electrical stimulation of the motor
stimulation).The patient is first instructed to squeeze
cortex using scalp electrodes, or by stimulation of the
the anesthesiologist’s hand, confirming that he is re-
anterior columns using epidural electrodes; conduction
sponsive, and then asked to move his feet and toes.
of these stimuli through the motor pathways is moni-
Patients usually respond within 5 minutes.
tored as peripheral nerve impulses, electromyographic
signals, or actual limb movements. As with SSEPs, If patient does not move hands or feet, 20 micro-
MEPs are very sensitive to N2O and potent inhalational grams increments of naloxone may be administered
agents, while subcortical SSEPs are more resistant. until response is obtained. This step may be needed
MEPs are also profoundly affected by benzodiazepines if narcotic boluses are used and not with infusions.
and thiopental, while ketamine may enhance MEPs. If hand movements are elicited but not feet, N2O is
Muscle relaxants will affect the intensity of the motor restarted and distraction on rod is released one notch,
response, which may lead to confusion interpreting and test repeated. If still no response is obtained, other
MEPs.

causes for paraplegia such as hematoma must be or severe gas exchange abnormalities such as
considered. Once test is elicited, anesthesia is quickly CO2 retention.
deepened with small doses of propofol (0.5 mg/kg) and
e. MV needs to be continued in those with central
muscle relaxant.
or peripheral causes of muscle weakness (Duch-
Complications of wake-up test: Recall is unusual enne’s muscular dystrophy, familial dysautono-
but is rarely viewed as unpleasant. Pain, excessive mia, severe cerebral palsy).
movement during wake-up, accidental extubation in
f. Residual effects of opioids or relaxants may cause
the prone position, myocardial ischemia, self-injury,
hypoventilation or apnoea, especially if associated
dislodgment of instrumentation, removal of IV and IA
with pre operative neuromuscular disease. Post-
lines, VAE with vigorous breathing are some of the
operative pneumothorax is also a risk. Incentive
complications. Wake-up test is difficult to perform in
spirometry, coughing and deep breathing should
young children or mentally deficient patients.
be encouraged to reduce risk of atelectasis and
Post-operative ventilator strategies and pain re- pneumonia.
lief
Although the long-term effect of scoliosis repair
Relevant details available in this case: is to halt the decline in respiratory function, pulmonary
function acutely deteriorates for 7 to 10 days after
- Preoperatively, had limitation of routine activity,
surgery.
dyspnea on mild to moderate exertion
Extubation
- Heart rate : 100/minute
Usual parameters for extubation are checked to
- Breath holding time : <10 seconds, RR-22/min at
decide on extubation (VC >10 mL/kg, VT >3 mL/kg,
rest
Spontaneous F < 30/min, inspiratory force > -30 cm
- CVS : Soft systolic murmur in pulmonary area H2O). Most posterior spinal fusion patients (with ac-
- Echo : Moderate PAH ceptable preoperative VC values) & most patients with
adolescent idiopathic scoliosis (with mild to moderate
- PFT : Restrictive pattern, VC 40% of predicted
pulmonary function abnormalities) can be extubated
immediately after surgery.
Post-operative ventilation Post-operative pain relief (4, 6)
Need for post-operative ventilation can be decided Patients experience considerable pain after mul-
considering following factors: tilevel spinal fusions with instrumentation.
a. Based on preoperative status in majority of pa- - Narcotic infusions may be continued but should
tients (clinical and investigative findings) be used judiciously with the goal of providing
adequate analgesia and to allow coughing and
b. Cobb Angles more than 65°are associated with
incentive spirometry without excessive respiratory
significant respiratory manifestations (in present
depression.
case-60°)
- For narcotic-tolerant patients, subanesthetic
c. In neuromuscular associated scoliosis, lesser
doses (0.2 mg/kg bolus, then 2 μg/kg/hr) of ket-
degrees (<30°) of angulation are associated with
amine has been found to be useful after posterior
severe impairment
spine fusions.
d. Reduction in V C to less than 40% predicts need
- Epidural Analgesia:
for post operative mechanical ventilation (MV).
MV should be continued in patients with severe Epidural catheter can be placed intraoperatively
restrictive lung defects (VC < 30% of predicted) by the surgeon.

Catheter can be placed at a level above the inci- References :

sion for lumbar fusions.
1. Enid R Kafer. Respiratory and cardiovascular functions
Two catheters, one towards the upper segments in scoliosis and the principles of anesthetic manage-
and another towards lower segments can be used ment.Anesthesiology.1980:52; 339-351
for effective analgesia with opioids and LAs. Two
2. Spinal surgery; Orthopedic Anesthesia ed. Denise J
catheters at different levels may overcome the
Wedel. 1993. Churchill Livingstone.;165-189
poor spread of epidural solutions.
3. Guidelines for the diagnosis and treatment of pulmonary
- NSAIDs may be used and benzodiazepines for
hypertension. Task Force for the Diagnosis and Treat-
muscle spasms may be beneficial.
ment of Pulmonary Hypertension of the European Soci-
- Intrapleural infusions of local anesthetics or opi- ety of Cardiology (ESC) and the European Respiratory
oids Society (ERS), endorsed by the International Society
of Heart and Lung Transplantation (ISHLT). European
- For procedures involving extensive spinal levels,
Heart Journal (2009) 30, 2493–2537
intrathecal morphine (2–5 μg/kg) administered
during surgery has been shown to provide reliable 4. Michael K Urban. Anesthesia for orthopedic surgery.
postoperative pain control. In Miller’s Anesthesia; Ed. Ronald D Miller; 7th edition;
Elsevier-Churchill;Livingstone;2010;2254-57
- Multimodal Analgesia: Multimodal technique
allows for effective analgesia with reduced risk of 5. Ralph L Bernstein, Andrew D Rosenberg. Manual of
respiratory depression. Epidural analgesia allow Orthopedic anesthesia and related pain syndromes;
patient-controlled epidural anesthesia infusions Churchill Livingston.1993;339-371
of local anesthetics and narcotics. Intrathecal
6. Anand H. Kulkarni, Ambareesha M. Scoliosis and An-
morphine (2–5 μgkg-1) during surgery may be
esthetic Considerations Indian Journal of Anesthesia
supplemented by PCA morphine.
2007; 51 (6): 486-495

Anesthetic Management of Tetralogy of Fallot Naheed Azhar
for Non Cardiac Surgery 299 Mahesh Vakamudi
01 ANESTHETIC MANAGEMENT OF TETRALOGY OF FALLOT

FOR NON CARDIAC SURGERY
Mahesh Vakamudi Naheed Azhar
Prof. & Head Associate Professor
SRMC, Vellore Medical College,
Chennai. Vellore.
A 4 year old boy who was diagnosed to have a main pulmonary artery (PA), or even in the peripheral
Tetralogy of Fallot was admitted for dental extraction. pulmonary arteries. Elevated pressures in the right
The child is on T. Propronalol 10 mg OD along with ventricle from right ventricular outflow obstruction and
iron and folic acid supplements as per the cardiologist’s exposure to systemic pressure from the overriding aorta
advice. lead to compensatory right ventricular hypertrophy.
On examination, central cyanosis present with What other diseases produce cyanosis in the first
clubbing of digits in all four limbs. The heart rate is year of life?
83/min, BP - 98/65 mm of Hg. Cardiac examination re-
Any condition that results in right-to-left shunting will
vealed an ejection systolic murmur over the left second
produce cyanosis. The classic cyanotic congenital
intercostal space close to the sternum and a single sec-
heart lesions are the 5 Ts:
ond heart sound. There were no peripheral signs of in-
fective endocarditis. The child is alert and well-oriented. • TOF
Laboratory examination revealed Hb-16gms%. • Transposition of the great arteries
Echocardiography confirmed the diagnosis of Tetralogy
• Truncus arteriosus
of Fallot. No vegetations were seen.
• Tricuspid atresia
Discussion
• Total anomalous venous return
• Pathophysiology and hemodynamic changes
Other cardiac lesions that lead to cyanosis are:
• Preoperative preparation of this child in relation
to its cardiac condition • Single ventricle
• Management of cyanotic spells • Hypoplastic left heart syndrome
• Intraoperative management • Double outlet right ventricle
• Postoperative care • Single atrium
What is Tetralogy of Fallot (TOF)? • Pulmonic stenosis (PS) or atresia
A congenital heart defect composed of four char- Describe the pathophysiology of TOF.
acteristics (a) large ventricular septal defect (VSD),
The main characteristic of TOF is cyanosis. Cy-
(b) right ventricular outflow obstruction, (c) over riding
anosis can result from three separate mechanisms:
aorta, and (d) right ventricular hypertrophy. The com-
(a) inadequate pulmonary blood flow, (b) right-to-left
plex of anatomic malformations results from an anterior
shunting, or (c) intrinsic pulmonary disease. In TOF, cy-
displacement of the conoseptum towards the right
anosis results from a right-to-left shunt at the level of the
ventricle creating a mal-alignment, VSD and a narrow-
ventricles and inadequate pulmonary blood flow. Be-
ing of the outflow tract of the right ventricle (RV). The
cause of the right ventricular outflow obstruction, blood
aorta is displaced anteriorly, straddling the muscular
ejected from the right ventricle crosses the VSD and
septum and arising from both ventricles (over riding of
enters the over riding aorta. This reduces the amount
aorta). The obstruction to outflow of the right ventricle
of pulmonic blood flow available for oxygenation and
usually involves the infundibulum of the right ventricle
adds desaturated blood to the systemic circulation
but can arise from the pulmonic valve, its annulus, the
leading to cyanosis. Pressures in the right ventricle

are near or equal to systemic pressure. The pressure shunt. The spasm can be treated with beta block-
load on the right ventricle causes the compensatory ers, with volume, and by deepening the level of
right ventricular hypertrophy. The degree of shunting anesthesia to decrease catecholamine levels.
across the VSD is proportional to the relationship of Morphine can be given to diminish the hyperpneic
PVR to systemic vascular resistance (SVR). Pulmonary response.
resistance is mostly fixed but can vary with activity. SVR
• Decrease in SVR
is variable. Decreases in SVR or increases in PVR will
worsen the degree of cyanosis. This will favor right-to-left shunting through the
VSD. Treatment is volume administration to en-
What are hypercyanotic spells? How are they
sure adequate filling of the right ventricle and an
treated?
alpha - adrenergic agonist to increase the SVR.
Hypercyanotic spells or “tet spells” are paroxys- SVR can also be increased by flexing the legs
mal episodes in which the cyanosis acutely worsens. or by compressing the abdominal aorta directly.
Crying, feeding, or defecating can bring on these epi- Children will squat during a hypercyanotic spell
sodes. The common pathway for all these activities is to increase their SVR and cause a decrease in
an increase in right-to-left shunting. Three mechanisms the right-to-left shunt.
can explain the increase in shunt:
To summarize
• Increase in PVR
• High FiO2 → pulmonary vasodilator → ↓ PVR
This is associated with a reduction in pulmonary
• Hydration (fluid bolus) → opens RVOT
blood flow and increase in right-to-left shunt.
Treatment is to lower PVR through hyperventila- • Morphine (0.1mg/kg/dose) → sedation,↓ PVR
tion with 100% O2 and bicarbonate administration • Ketamine → ↑ SVR, sedation, analgesia → ↑
to temper the effects of acidosis on PVR. PBF
• Dynamic outflow obstruction • Phenylephrine (1mcg/kg/dose) → ↑ SVR
Tachycardia, hypovolemia and increased myo- • β-blockers (Esmolol 100-200mcg/kg/min) → ↓HR,
cardial contractility can cause infundibular spasm. -ve inotropy → improves flow across obstructed
Similar to an increase in PVR, spasm decreases valve &↓ infundibular spasm
blood flow into the PA and worsens right-to-left
What syndromes can be associated with TOF?
Syndrome Lesion Cardiac Lesion Comments

Syndromes with Airway Issues and CHD
Micrognathia, possible difficult
CHARGE association VSD, ASD, PDA, TOF
airway
Maxillary and mandibular
Goldenhar's
VSD, PDA, TOF, CoA hypoplasia, C-spine anomalies—
syndrome
difficult intubation
Miller-Dieker Microdeletion
TOF, VSD,PS
syndrome 17p13.3
Coloboma, heart, choanal
VSD, ASD, PDA,
CHARGE association atresia, retardation, genital
TOF
and ear anomalies

What are the commonly associated anomalies with ο Central shunt: artificial tube graft between
TOF? the aorta and PA
Associated cardiac anomalies are: Other shunts such as the Waterston and Potts
shunts are of historic interest now.
• Multiple muscular VSDs (about 3% to 15%)
Definitive surgical correction.
• Right-sided aortic arch (25%)
About 70% of patients with TOF with PS require
• Atrial septal defect (ASD) (9%)
surgery within the first year of life. In the past, children
• Persistent left superior vena cava (8%) underwent placement of a systemic-pulmonary shunt
• Abnormalities in the coronary arterial origin and followed by a definitive repair at an older age. As sur-
distribution (5%) gical and anesthetic techniques improved, corrective
surgery was undertaken at a younger age. Currently,
• PDA (4%) most patients with TOF have a full correction between
• Partial anomalous pulmonary venous drainage the ages of 2 to 10 months. The diagnosis of TOF is
(1%) made at or soon after birth. The infants are followed
until evidence of hypercyanotic episodes occur and
What are the significant variables in TOF? then referred for surgery. A push had been made for
The variables in TOF are the location and degree neonatal correction of this disease, but the increased
of right ventricular outflow obstruction and the size of surgical morbidity and mortality did not support surgery
the VSD. These factors, coupled with the relationship at that early age.
of PVR to SVR, all influence the amount of right-to-left The definitive correction of TOF requires CPB
shunting. The right ventricular outflow obstruction and includes closure of the VSD with a patch, a right
can range from mild to complete (TOF with pulmonary ventriculotomy with division of muscle bundles, and
atresia). The location of the obstruction can be any- enlargement of the RV outflow tract. The outflow
where along the right ventricular outflow-infundibulum, augmentation is done with a pericardial patch that
pulmonic valve, the annulus of the pulmonic valve, the can include the outflow tract, valve annulus, and even
main PA, or in the branch or peripheral pulmonary arter- extend onto the main and branch pulmonary arteries.
ies. VSD size can limit the amount of blood shunted into The closure of the VSD is completed with a patch that
the aorta. Infants with less shunt and smaller degrees closes the defect and leaves the aorta arising from only
of cyanosis have improved outcomes. the left ventricle. Nothing is done to the overriding aorta.
What techniques or surgical procedures are avail- Following correction, the pressures in the right ventricle
able for treating TOF? should be at least half of the systemic pressure.
Palliative procedures The only contraindication to a repair after the

first 2 months of life is an anomalous origin of the
• Balloon dilatation of the pulmonic valve can be
right coronary artery. In this case a shunt procedure
performed during catheterization.
is done initially, followed by reconstruction with RV to
• Systemic-pulmonary arterial shunts PA conduit at a later date.
ο Classic Blalock-Taussig shunt: anastomosis Patients with TOF with pulmonary atresia require
of the right or left subclavian artery to the a more complex correction involving reconstruction
PA of their pulmonary arteries with multiple surgeries as
ο Modified Blalock-Taussig shunt: artificial well as closure of the VSD. Initially the outflow tract
tube graft between the right or left subclavian obstruction is relieved, the VSD is left open, and the
artery and pulmonary arteries pulmonary circulation is reconstructed in a unifocal-
ization procedure. The concept of unifocalization is

to use the largest of the aortopulmonary collaterals patients need to be addressed. Recent respiratory
to “build” right and left pulmonary arteries. The newly tract infection and the presence of loose teeth should
constructed pulmonary arteries can be connected to be noted.
the right ventricle with homograft, allowing flow from
Hematocrit is frequently elevated in cyanotic pa-
the right ventricle into the pulmonary arteries and to
tients and intraoperative phlebotomy can be used to
help them grow. Eventually, the VSD is closed and
prevent the problems associated with polycythemia.
any residual outflow tract stenosis is relieved. When
Chest radiographs demonstrate a boot-shaped heart
necessary a valved homograft is interposed between
secondary to right ventricular hypertrophy and concave
the RV and the PA.
PA segment.
Preoperative assessment should include?
An extensive cardiac evaluation to identify other
A preanesthesia history and physical examination, congenital anomalies is prudent. Cardiac catheteriza-
accompanied by appropriate laboratory data, are vital. tion can provide information on PVR, the ratio of pulmo-
Special attention is directed to information pertaining nary blood flow to systemic blood flow (Qp:Qs), and de-
to hypercyanotic spells—frequency, severity, and gree of valvar PS. Angiography will display the coronary
methods to treat them. Weight gain, growth, develop- and PA anatomy, pulmonary collateral circulation, and
ment, and level of activity can indicate the severity of other cardiac anomalies. Much of this information can
the cardiac disease. An understanding of the patient’s be gathered from transthoracic echocardiography.
medications and their effects is also necessary. In Should all cardioactive drugs be continued upto
addition, common preoperative problems for pediatric surgery?
Cardiac drug class Interactions Considerations

Consider withholding AM dose, or
reducing dosage, in hypotensive
Angiotensin-
Hypotension with induction of general patients; avoid fixed dose
converting enzyme
anesthesia induction regimens with drugs
inhibitors
having a profound vagomimetic
effect
Acute withdrawal can precipitate tachycardia
and arrhythmias; can potentiate hypotension Continue in the perioperative
ȕ-Blockers
with volatile anesthesia; can decrease period
response to inotropic agents
Calcium channel May augment the negative inotropic and Continue in the perioperative
blockers chronotropic effects of volatile anesthesia period
Hypovolemia/hypokalemia;may augment effect
Diuretics Discontinue preoperatively
of neuromuscular blocking agents
Can be proarrhythmic with inotropes,
electrolyte disturbances; high Avoid electrolyte imbalance
Antiarrhythmics catecholaminergic states; can interact with Avoid drugs that are
other antiarrhythmics and precipitate proarrhythmic. Monitor carefully
bradycardia
Reduces perioperative shivering, ischemia, Continue into the perioperative
Į2-Agonists
anesthetic and analgesic requirements period with appropriate monitoring

What NPO guidelines do you follow and what pre- Is infective endocarditis prophylaxis mandated?
medication do you give?
High risk - Previous infective endocarditis, prosthetic
General NPO guidelines can be followed. The heart valves, complex congenital cyanotic heart dis-
child is allowed any solid food and particulate fluid ease, surgically constructed systemic or pulmonary
(like milk, formula, or breast milk) up to 6 hours before conduits
surgery and clear liquids up to 2 hour before surgery.
Moderate risk - Non-cyanotic heart disease not men-
Fasting guidelines for pediatric patients tioned elsewhere, Mitral valve prolapse with valvular
regurgitation
Fasting Time (hr)
Age Milk and Solids Clear Liquids Negligible risk - Isolated secundum ASD, 6 months
<6 months 4 2 after surgical repair of ASD, VSD or ligation of PDA
6-36 months 6 3 Mitral valve prolapse without regurgitation, physi-

ological, functional or ìnnocent’ heart murmurs, cardiac
>36 months 8 3
pacemakers
Oral premedication is recommended in children
Yes. Antibiotics should be administered intrave-
who suffer from hypercyanotic spells. Midazolam 0.5
nously before induction, if possible. In the event that
to 1.0 mg/kg can be given by mouth 10 to 20 minutes
intravenous access is obtained after induction, antibi-
before induction in children older than 9 months or
otics should be given as soon as possible. In patients
pentobarbital 2 to 4 mg/kg 45 minutes before induction
with no known allergies, cefazolin 25 mg/kg is appro-
in children older than 6 months. Alternative drugs like
priate. If there is a penicillin or cephalosporin allergy,
ketamine, mepredine have been tried. An anticholin-
vancomycin 20 mg/kg over 1 hour can be substituted.
ergic agent, atropine 0.1 to 0.15 mg/kg by mouth, can
Antibiotics should be repeated after separation from
prevent bradycardia associated with some anesthetic
inductions. Propranolol should be continued up to and CPB.
including the day of surgery.
Single dose 30-60 min before

dental procedure
Situation Drug Adults Children
Oral Amoxicillin 2g 50 mg/kg
Unable to take oral medication Ampicillin or 2 g IM/IV 50 mg/kg IM/IV
Cefazolin/ceftriaxone 1 g IM/IV 50 mg/kg IM/IV
Allergic to penicillins/oral Cephalexin or 2g 50 mg/kg IM/IV
Clindamycin or 600 mg 20 mg/kg IM/IV
Azithromycin/clarithromycin 500 mg 15 mg/kg
Allergic to penicillins/unable to take
Cefazolin/ceftriaxone or 1 g IM/IV 50 mg/kg IM/IV
oral medication
Clindamycin 600 mg 20 mg/kg
Which emergency drugs will you prepare? dition, phenylephrine 2 to 10 mcg/kg and propranolol
10 to 50 mcg/kg should be available to assist in the
Standard emergency drugs for pediatric cardiac
treatment of hypercyanotic spells. Infusions should be
case should be available. Epinephrine 10 mcg/kg,
readily available if inotropic support is necessary in the
atropine 20 mcg/kg, calcium chloride 10 mg/kg. In ad-

postbypass period. Dopamine, dobutamine, isoprotere- • Decrease PVR to maintain or improve pulmonary
nol, epinephrine, or phosphodiesterase inhibitors are blood flow. Hypercarbia, hypoxia, light anesthesia,
all useful in these cases. atelectasis, polycythemia, acidosis, and elevated
airway pressures increase PVR. Hypocarbia, ane-
What monitoring will be necessary for such a
mia, alkalosis, high oxygen concentrations, and
patient?
deep anesthesia decrease PVR. PVR can also
Standard monitoring includes be decreased using drugs such as nitroglycerin,
• Electrocardiogram (ECG) sodium nitroprusside, phentolamine, tolazoline,
prostaglandin E1, or inhaled nitric oxide.
• Pulse oximetry. Because pulse oximeters require
pulsatile flow to work properly, the probe should • Favor mild myocardial depression and euvolemia
be placed on the hand opposite to the side of the because they can help prevent or limit a hyper-
proposed shunt. Appropriate care in placing the cyanotic spell. Most volatile anesthetics provide
pulse oximeter will prevent a loss of signal dur- some myocardial depression with halothane hav-
ing shunt placement. Occasionally, two sites are ing the most pronounced effect.
selected—one probe on an upper extremity and • Slow heart rate to reduce the likelihood of in-
a second probe on a lower extremity. fundibular spasm.
• Blood pressure. An automated blood pressure cuff If intravenous access is present, induction can
can be used during induction. After endotracheal be accomplished with ketamine (2 mg/kg) or fentanyl
intubation, an arterial line can be placed if deemed (25 mcg/kg). An intravenous induction is faster in pa-
necessary. The need for this line is surgeon and tients with a right-to-left shunt because peak receptor
patient dependent. The site of arterial cannulation site concentrations are attained faster. If intravenous
should avoid arteries affected by the current pro- access is absent, induction can be accomplished with
cedure or previous shunts. An arterial line allows an intramuscular injection of ketamine (4 mg/kg) espe-
for continuous blood pressure measurement and cially in patients in whom a mask induction would be
access for arterial blood gas sampling. frightening. The option of a mask induction with oxygen
• End-tidal carbon dioxide. This helps determine and halothane or sevoflurane is always a possibility,
correct placement of the endotracheal tube and keeping in mind that a significant right-to-left shunt
assists in managing ventilation. may delay induction. Once the induction is completed
and intravenous access is established, vecuronium
• Rectal and esophageal temperature
or pancuronium (0.2 mg/kg) can be given to facilitate
• Urine output endotracheal intubation. Maintenance of anesthesia is
accomplished with oxygen, volatile anesthetic agents,
At least one, but preferably two, large bore intra-
intravenous opiates, and benzodiazepines. An appro-
venous line(s) are placed after induction.
priately sized endotracheal tube should be placed ac-
What are the goals of the anaesthetic technique in cording to the size and age of the patient. Intravenous
a patient with TOF? tubing must be meticulously checked to ensure that no
The main goal of induction in a cyanotic patient air bubbles enter the patient’s circulation.
is to establish a necessary level of anesthesia without How would you manage an uncorrected patient for
increasing the right-to-left shunt. The stress of the noncardiac surgery?
induction can lead to a hypercyanotic spell. The objec-
The management of a patient with TOF undergo-
tives are to:
ing noncardiac surgery is directed at prevention of hy-
• Maintain SVR. Avoid drugs that decrease SVR percyanotic spells. A complete history of the frequency,
and treat decreases in blood pressure promptly severity, and causes of hypercyanotic spells as well as
with vasoconstrictors. the methods used to treat them are important. Hemat-

ocrit, shunt fraction, and overall health of the patient are degree of hypoxemia, the presence of acidosis, and
essential pieces of information. The severity of resting serial hematocrits. Keep in mind the location of shunts
cyanosis and the hematocrit can indicate severity of when placing the blood pressure cuff or arterial line.
the right-to-left shunt. Risk is increased in patients with
Can Inhalational Induction be safely performed in
more severe cyanosis or with hypercyanotic episodes.
TOF?
Patients who have a systemic-to-pulmonary artery
shunt have a lower risk. Inhalation inductions are generally well received
and tolerated by most children. An inhalation induction
Anesthetic goals are the same as if the procedure
with sevoflurane can easily and safely be performed
was cardiac surgery—maintain SVR and improve
even in cyanotic patients such as those with tetralogy
pulmonary blood flow. Be prepared to treat a tet spell
of Fallot. In these patients, who are at risk for right-to-
aggressively with fluids, negative inotropes, oxygen,
left shunting and systemic desaturation, oxygenation
hyperventilation, and vasoconstrictors.
is well maintained with a good airway and ventilation
Monitoring should be standard. A noninvasive despite halothane-induced reduction in systemic
blood pressure cuff is sufficient for most routine cases, arterial pressure. Skilled airway management and ef-
but longer or more complex cases warrant arterial ficiency of ventilation are equally essential components
access. Arterial blood gas analysis can assess the of anesthetic induction.
What are the Factors affecting pulmonary vascu-
lar resistance (PVR)?
Decrease in PVR Increase in PVR

Increasing PaO2 Sympathetic stimulation
Hypocarbia Light anesthesia
Alkalemia Pain
Minimizing intra-thoracic pressure Acidemia
Spontaneous ventilation Hypoxia
Normal lung volumes Hypercarbia
High frequency and jet ventilation Hypothermia
Avoidance of sympathetic stimulation Increased intrathoracic pressure
Deep anesthesia Controlled ventilation
Pharmacological methods PEEP
Isoprenaline Atelectasis
Phosphodiesterase III inhibitors
Prostaglandin (Pg) infusion (PgE1 and PgI2)
Inhaled nitric oxide
What is the effect of anesthetic agents on pulmo- Halothane and sevoflurane are both considered
nary vascular resistance (PVR)? safe for inhalation induction. They both decrease SVR
but have a small effect on PVR. Sevoflurane is less of
Barbiturates have a vasodilating effect, lowering
a myocardial depressant than halothane.
both SVR and PVR.
Desflurane and isoflurane decrease SVR in a
Ketamine has been shown to decrease PVR in
dose-dependent manner and are mild myocardial de-
adults but not in children. Its sympathomimetic effect
pressants. Desflurane at higher concentrations (above
helps in maintaining SVR, and it is considered one of
6%) is associated with increased sympathetic stimula-
the safest induction techniques for a cyanotic patient.
tion, which can be detrimental in TOF. Both volatile
Narcotics provide good hemodynamic stability agents have a very pungent odor and have been as-
without altering PVR. Fentanyl and sufentanil are used sociated with laryngospasm and bronchospasm, during
for maintenance of anesthesia because they blunt the inhalational induction, can be used for maintenance of
sympathetic stress response. anesthesia.
Nitrous oxide does not increase PVR in infants, to reach the thoracic epidural space. A combination
but 100% oxygen is preferred to avoid hypoxemia. of bupivacaine and fentanyl, or bupivacaine and mor-
phine, can be used as an infusion and with the dose
How are hypercyanotic spells managed during
adjusted as needed. For the postoperative period, an
anesthesia?
infusion of 0.10% bupivacaine plus fentanyl 2 mcg/mL
Hypercyanotic spells manifest with a sudden is given at a rate of 0.3 mL/kg/hour.
decrease in the oxygen saturation. Without quick
If anticoagulation is planned, placement of a spinal
intervention, they can progress to bradycardia and
or epidural anesthetic should occur soon after intuba-
systemic hypotension. Treatment is to increase the
tion to maximize the time before anticoagulation. The
depth of anesthesia, hyperventilate with 100% oxygen,
most common side effects of neuraxial narcotics are
administer volume, increase SVR with phenylephrine,
nausea, vomiting, and pruritus. Hypotension associated
and decrease infundibular spasm with beta-blockers.
with use of epidural local anesthetics in adults is very
Sodium bicarbonate should be considered to treat any
uncommon in children. The risk of epidural hematoma
ensuing metabolic acidosis.
is small. The epidural catheter should be removed only
Can regional anesthesia be used alone or with GA after return of normal coagulation parameters postop-
in a patient with TOF? eratively.
Use of regional anesthesia techniques in children What are the requirements for extubation?
seems to be more effective in inhibiting the stress
Extubation following an elective procedure can
response associated with surgery than intravenous
usually be accomplished soon after the completion of
narcotics. Spinal injection of narcotics and/or local
surgery. Spontaneous ventilation with normal blood
anesthetics achieves an excellent pain relief allowing
gases, normothermia, adequate pain control, and
extubation in the operating room after procedures that
stable hemodynamics are required before extubation.
do not require CPB. A combination of local anesthetic
Extubation is usually performed in the operating room
and narcotic given in the caudal or epidural space at
or soon after arrival in the intensive care unit.
the beginning of the case can dramatically decrease
the amount of total narcotic required for the case. In emergency surgeries the patient may be un-
stable before surgery. The probability of hemodynamic,
Continuous epidural infusion during surgery
metabolic, and pulmonary problems is high. As such,
attenuates the stress response and helps optimize
extubation in these patients should wait until resolution
analgesia in the postoperative period. In children,
of these issues. Other important issues to be consid-
epidural catheters can be easily inserted through the
ered are postoperative bleeding, the need for inotropic
sacrococcygeal membrane and advanced 16 to 18 cm
support, and cardiac and pulmonary function.

Anesthetic management of transurethral resection Venkatachalam T
of prostrate 307 Aruna Parameswari
01 ANESTHETIC MANAGEMENT OF TRANSURETHRAL

RESECTION OF PROSTRATE
Professor, MMC, Chennai. Venkatachalam T

Professor,SRMC, Chennai. Aruna Parameswari
1. What is the nerve supply of the prostate? 3. What are the features of an ideal irrigating
solution?
The nerve supply to the prostate arises from the
prostatic plexus, which originates from the inferior hy- The ideal irrigation fluid should be
pogastric plexus, and carries both sympathetic fibres
• Transparent (for good visibility)
from T11 to L2 and parasympathetic fibres from S2 to
S4. Pain fibres from the prostate, prostatic urethra, and • Electrically non-conductive (to prevent dispersion
bladder mucosa originate primarily from sacral nerves of the diathermy current)
S2 to S4. Pain signals from bladder distension travel • Isotonic
with sympathetic fibres and have their origin in T11- L2.
• Non-toxic
The sensation of stretch in the bladder (proprioception)
is carried by the parasympathetic fibres of S2 – S4. • Non-hemolytic when absorbed
2. What is the function of the irrigation fluid in • Non-metabolized and excreted rapidly when ab-
TURP? sorbed
The bladder is continuously irrigated with fluid to • Easy to sterilize
facilitate clear vision of the surgical field, to distend the
• Inexpensive (given the large volume that is neces-
operative site and to wash away blood and dissected
sary)
tissue debris.
Solutions Osmolality Advantages Disadvantages
(mOsm/L)
Distilled water 0 Improved visibility Hemolysis
Hemoglobinemia
Hemoglobinuria
Hyponatremia
Glycine (1.5%) 200 Less likelihood of TURP Transient postoperative visual
Glycine (1.2%) 175 syndrome loss syndrome
Hyperammonemia
Hyperoxaluria
Sorbitol 165 Same as glycine Hyperglycemia, possible
(3.3%) lactic acidosis
Osmotic diuresis
Mannitol (5%) 275 Isosmolar solution Osmotic diuresis
Not metabolized Possibility of acute
intravascular volume
expansion
Cytal 178 Same as sorbitol and Same as sorbitol and
mannitol mannitol
Glucose 139 Less likelihood of TURP Hyperglycemia
(2.5%) syndrome
Urea (1%) 167 Less likelihood of TURP -
syndrome

4. Name some irrigating solutions that have could be responsible for the transient blindness seen in
been used with their advantages and disad- these patients. The redistribution half life of glycine is 6
vantages. min and the terminal half-life which is dose-dependent
varies from 40 min to several hours. Hyperoxaluria
Prostate has a rich blood supply and venous drain-
from metabolism of glycine into oxalate and glycolate
age is via the large, thin-walled sinuses adjacent to the
has been proposed as a mechanism of renal failure in
capsule. If the irrigating fluid infusion pressure exceeds
susceptible patients with the use of glycine.
the venous pressure during a TURP procedure, the lush
venous plexus of the prostate may allow intravascular 5. What is the amount of irrigation solution that
absorption of the irrigating fluid. gets absorbed during TURP? How can exces-
sive fluid absorption be avoided?
Absorption of any irrigating solution can cause
overhydration , volume overload and pulmonary edema Factors that predict the amount of irrigation fluid
and all but the balanced salt solutions cause dilutional absorption during a TURP procedure include the num-
hyponatraemia. ber and size of open venous sinuses (large blood loss
implies a large number of open veins and a potential for
Hypotonicity makes distilled water an unaccept-
irrigation absorption), duration of resection, hydrostatic
able irrigating solution as intravascular absorption of
pressure of the irrigating fluid (height of the container
distilled water (with an osmolality of 0 mOsm/L) in large
of irrigating solution above the surgical table), and
quantities causes dilutional hyponatremia, intravascu-
venous pressure at the irrigant-blood interface. Mas-
lar hemolysis, hemoglobinemia, hemoglobinuria and
sive absorption is more likely if intravesicular pressure
renal failure. So, distilled water is no longer used as
increases above 30 mm Hg. Usually, 10 – 30 ml of
an irrigating solution for TURP. It is only used as an
irrigation solution gets absorbed per minute of resec-
irrigating solution for procedures without the possibility
tion time. 5 – 20% of patients will absorb > 1 litre. Low
of absorption, like cystoscopy.
venous pressure, e.g., if the patient is hypovolaemic
Solutions are made purposely hypotonic to pre- or hypotensive favours absorption of irrigation solution.
serve their transparency. Nearly isotonic solutions Capsular perforation, or bladder perforation, allows a
used include balanced electrolyte solutions (Ringer’s large volume of irrigation fluid into the peritoneal cavity,
Lactate), sorbitol (3.5%), mannitol (5%), Cytal (a from where it is rapidly absorbed.
mixture of sorbitol 2.7% and mannitol 0.54%), glycine
To avoid excessive fluid absorption, procedural
(1.2% and 1.5%), urea (1%) and glucose (2.5 – 4%).
guidelines include limiting resection time to < 1 hour,
The conductivity of balanced electrolyte solutions such
and suspending the irrigating fluid bag no more than
as Ringer’s Lactate interferes with electrocautery and
30 cm above the operating table at the beginning and
disperses electrical current from the resectoscope,
15 cm in the final stages of resection. If intravesical
potentially posing a risk to patient and surgeon. Sorbitol
pressure is kept below 15 cm H2O, absorption virtually
and glucose cause significant hyperglycaemia.
ceases. Leaving a rim of tissue on the capsule until near
Glycine, a non-essential amino acid, is normally the end of the procedure, where it can either be left (if
metabolized by oxidative transformation in the liver and signs of TURP syndrome are evident) or removed all
kidneys into glyoxylic acid and ammonia. Accumulation at once, may reduce the time that a large number of
of ammonia can lead to depressed mental status and prostatic sinuses are open and thus capable of absorb-
coma. Glycine can also cause negative hemodynamic ing fluid.
changes and visual disturbances, including blurred vi-
6. How long is irrigation continued after the sur-
sion and transient blindness. Visual disturbances due to
gery and what irrigating solution is used?
glycine are likely because of a peripheral mechanism,
such as brainstem or cranial nerve inhibition and a A 3 lumen catheter is inserted at the end of the
neurological pathway disturbance, rather than cerebral operation, to allow continuous irrigation for upto 24
edema. An inhibitory action of glycine on the retina hours after the operation using normal saline.

7. What are the indicators of volume gain during lithotomy position is also associated with reduced tidal
TURP? volume and functional residual capacity, decrease in
vital capacity, decrease in pulmonary compliance and
The most widely used indicator of volume gain is
increases the likelihood of gastric regurgitation. Cardiac
the serum sodium dilution or breath alcohol level. Etha-
preload may increase. Nerve injuries to the common
nol 1% can be added to the irrigation solution and the
peroneal, sciatic and femoral nerves are likely.
patient’s breath is tested for ethanol every few minutes.
A positive test indicates a significant quantity of fluid Resumption of the supine position from lithotomy
has been absorbed. Other methods follow volumetric could result in venous stasis in the lower limbs and fall
fluid balance, CVP trend, plasma electrolyte concentra- in blood pressure, at the end of the procedure.
tions (e.g. magnesium and calcium), irrigation solutes
Surgery related
(glycine, sorbitol), transthoracic impedance change
and the patient’s weight gain. The potential problems during TURP are:
8. What are the anesthetic concerns in a patient Intraoperative

posted for TURP? • TURP syndrome
Patient related • Hemorrhage
Patients are usually elderly, and may have co- • Myocardial ischemia
existing diseases involving various organ systems. In
• Hypothermia
one large series, the average age of the patient was 69
years and only 23% did not have a significant medical • Prostatic capsular perforation
condition before surgery. In this study, the most com-
• Bladder or urethral perforation
mon associated medical conditions were: Pulmonary
(14.5%), gastrointestinal (13.2%), myocardial infarction • Penile erection
(12.5%), cardiac arrhythmias (12.4%), renal insuf- Postoperative
ficiency (9.8%) and diabetes (9.8%).
• TURP syndrome
Pre-operative assessment should include a de-
• Bladder spasm
tailed history and physical examination. Laboratory
investigations should include a complete blood count, • Ongoing bleeding
renal function test, electrolytes, electrocardiograph and
• Clot retention
chest radiograph, if indicated. Special attention should
be paid to the cardiovascular status, especially heart • Deep venous thrombosis
failure, as fluid absorption increases the risk. Chronic • Myocardial ischemia/infarction
prostatic hypertrophy may cause obstructive renal in-
• Postoperative cognitive impairment
sufficiency. Urine analysis is mandatory to exclude a
urinary tract infection, as this, if left untreated, increases 9. What is TURP syndrome?
the risk of postoperative septicemia. Blood grouping
The TURP syndrome is essentially a clinical di-
and cross matching is needed for anemic patients and
agnosis based upon a constellation of symptoms and
those suspected of having large prostates on examina-
signs associated with excessive absorption of irrigat-
tion and ultrasound scan.
ing fluid into the circulation. The irrigation fluid either
Positioning related gains direct intravascular access (through the prostatic
venous plexus), or is more slowly absorbed from the
TURP is done in the lithotomy position which in
retroperitoneal and perivesical spaces. It comprises
elderly patients with osteoarthritis or prosthetic joints
acute changes in intravascular volume, plasma solute
is associated with positioning difficulties and increased
concentrations, and osmolality, and direct effects of the
risk of musculoskeletal injury and pressure sores. The

irrigation fluid used. The effects are proportional to the reflex bradycardia. It can also lead to acute cardiac
volume of irrigating solution absorbed. The presenta- failure and pulmonary edema.
tion is not always uniform, and milder cases may be
Rapid equilibration of hypotonic fluid with the
unrecognized. Other types of endoscopic surgery that
extracellular fluid compartment may precipitate sud-
require the use of irrigation solution, e.g. hysteroscopy,
den hypotension in association with hypovolemia.
may also give rise to a syndrome like the TURP syn-
Hypotension and hypovolemia may be compounded
drome.
by the sympathetic block of spinal anesthesia.
Mild-moderate TURP syndrome may occur in
Solute changes
1-8% of patients. The overall mortality is 0.2-0.8%. It
may present as early as 15 min after resection starts Hyponatraemia and Hypoosmolality
or as late as 24 h after operation. This is because the Acute changes in plasma sodium concentration
patient’s serum sodium concentration and osmolal- and osmolality predominantly affect the central nervous
ity may continue to decrease for some time after the system. Acute hyponatraemia is initially produced by
procedure, because much irrigant is slowly absorbed the dilutional effect of a large volume of absorbed irriga-
from the perivesicular and retroperitoneal spaces. tion fluid, but later is caused by natriuresis. It can cause
The syndrome is due to intravascular volume headache, altered level of consciousness, nausea,
changes and/or solute changes. vomiting, seizures, coma and death. The cardiovascu-
lar effects of severe hyponatraemia include negative
Volume changes
inotropy, hypotension and dysrhythmias. The signs and
Acute volume changes predominantly affect the symptoms of acute hyponatraemia are related to the
cardiovascular system, causing hypertension with serum sodium level:
Serum NaЀ level CNS Changes ECG Changes

120 Confusion, restlessness Possible widening of QRS complexes
115 Somnolence, nausea Widened QRS complex, Elevated ST segment, T wave
inversion
110 Seizures, coma Ventricular tachycardia or fibrillation
Hypoosmolality is more important than hypona- cerebral edema and raised intracranial pressure, which
traemia in causing CNS disturbances. This is to be results in bradycardia and hypertension by the Cush-
expected because the blood brain barrier, with an ef- ing’s reflex.
fective pore size of 8 Å, is essentially impermeable to Hence, serum sodium concentration should be
sodium but freely permeable to water. The Nernst equa- measured in conjunction with serum osmolality.
tion predicts that a moderate decrease in extracellular
sodium concentration only minimally alters membrane The classic triad of symptoms of TURP syndrome
excitability. Patients who are hyponatraemic but have a under regional anesthesia include increase in both
normal osmolality are likely to be asymptomatic. Rapid systolic and diastolic pressures associated with an
reduction in plasma osmolality overwhelms neuronal increase in pulse pressure, bradycardia and mental
compensatory mechanisms. Free water is absorbed status changes.
into the brain parenchyma, causing water intoxication, Signs and symptoms of TURP syndrome
CVS and RS CNS Metabolic Other
Hypertension Agitation/Confusion Hyponatremia Hypo-osmolality
Dysrhythmias Seizures Hyperglycinemia Hemolysis
Congestive heart failure Coma Hyperammonemia
Pulmonary edema and Visual disturbances
hypoxemia (blindness)
Myocardial infarction

Hyperammonemia Later, the patient may develop respiratory dis-

tress, pulmonary edema, hypoxia, nausea, vomiting,
Hyperammonemia due to metabolism of glycine
confusion, convulsions and coma. Glycine may also
may contribute to alteration in CNS function; however,
directly depress the myocardium. NMDA receptor activ-
the exact role of hyperammonemia in TURP syndrome
ity is potentiated by glycine, which paradoxically may
remains unclear. In the treatment of hyperammone-
precipitate encephalopathy and seizures. Magnesium
mia, the methods for limiting the increase of plasma
(whose plasma level may also be reduced through
ammonia concentration when glycine irrigants are
dilution) exerts a negative control on the NMDA recep-
used include L-arginine, which acts in the liver by pre-
tor and also has a membrane stabilizing effect, and
venting hepatic release of ammonia and accelerating
magnesium therapy should be considered as part of
ammonia conversion to urea. The time necessary to
the therapy for seizures in TURP syndrome.
deplete endogenous arginine stores may be as little as
12 hours, which approximates preoperative fast time. 5. Describe the management of TURP syn-
Prophylactic administration of intravenous L-arginine drome.
can markedly moderate the rise in blood ammonia
If TURP syndrome is suspected, surgery must be
concentration. Doses between 4 g (20 mmol) infused
abandoned as soon as possible and intravenous fluids
over 3 minutes and 38 g (180 mmol) infused over 120
stopped. Treatment should involve supporting respira-
minutes have been recommended. The osmolality of
tion (administering 100% oxygen, intubation and venti-
10% L-arginine solution is 950 mOsm/kg.
lation, if necessary) and the circulation (using inotropes
Hyperglycinemia and vasopressors). Bradycardia and hypotension
should be treated with atropine and adrenergic drugs.
Glycine is a major inhibitory neurotransmitter like
IV anticonvulsants should be used to control seizures
γ-amino butyric acid (GABA) in the spinal cord and mid-
and IV magnesium therapy should be considered in
brain and may have a significant role in higher cortical
refractory seizures.
neurotransmission. It can cause encephalopathy due
to its role as an inhibitory neurotransmitter and due to Blood should be obtained and tested for sodium,
facilitation of excitatory neurotransmission in the brain osmolality and hemoglobin and arterial blood gas
through an allosteric activation of the NMDA recep- analysis. 12 lead ECG should be obtained.
tor.
Diuretic therapy (IV Furosemide 40 mg) is only
When glycine 1.5% is used as the irrigation fluid, recommended to treat acute pulmonary edema caused
early features of this syndrome include restlessness, by the transient hypervolemia. Furosemide worsens
headache, tachypnea and a burning sensation in the hyponatraemia, but is effective in removing free water.
face and hands. Visual disturbances including transient Mannitol causes less sodium loss than loop diuretics.
blindness can occur. Normal plasma glycine levels
Hypertonic saline (3%) is indicated to correct se-
are 13 – 17 mg/L, whereas levels of 1029 mg/L were
vere hyponatraemia, if serum sodium < 120 mmol/L,
measured during one episode of blindness. Patient with
or if severe symptoms develop. The rate of correction
visual disturbances present with sluggish or fixed and
should be slow (not > 1 mmol/L/h in the first 24 h) at
dilated pupils and total loss of light/dark discrimination.
< 100 ml/h. The amount needed is calculated as fol-
Atropine or hyponatremia and cerebral edema may
lows:
contribute to these visual disturbances. Patients with
cortical blindness, however, lose all visual sensation Calculate total body water as 0.6 x body weight (kg),
(light perception and the blink reflex) but retain the e.g. for a 70 kg man, TBW = 42 litre
papillary responses to light and accommodation. There- 2 x TBW is the number of milliliters of NaCl 3% which
fore, glycine appears to affect the retinal physiological will raise serum [Na] by 1 mmol/L;
condition independent of cerebral edema caused by
e.g. 2 x 42 = 84 ml of NaCl 3% over 1 hour will raise
hypo-osmolality.
serum sodium by 1 mmol/L
Too rapid a correction may lead to hypervolemia, and tends to mitigate intraoperative fluid overload.
cerebral edema and central pontine myelinolysis due to However, when the block dissipates, venous capacity
rapid increases in plasma osmolality. As demyelination acutely decreases, and circulatory overload can occur.
can occur in extrapontine areas as well, the disease is The lower CVP associated with RA may increase the
also referred to as “osmotic demyelination syndrome”. absorption of irrigation fluid.
The demyelination is the result of excessive shrinkage
In addition, the incidence of deep vein thrombosis
of brain cells after rapid hydration with hyperosmolar
is decreased with regional anesthesia. This is because
solution as the brain cells have extruded important
RA decreases the hypercoagulable tendency in the
osmoles to compensate for the hypotonicity. Correc-
postoperative period due to modulation of the neuroen-
tion to normal serum sodium level is not indicated: the
docrine response to tissue injury.
aim should be clinical improvement. Hypertonic saline
should be administered through a large vein. Satisfactory regional anesthesia for TURP
involves achieving an anesthetic block level that in-
Invasive monitoring of arterial and central venous
terrupts sensory transmission from the prostate and
pressures is very helpful in managing patients with
bladder neck, and blocks the uncomfortable sensation
large fluid shifts. Transferring the patient to an ICU
of distension of the urinary bladder. A sensory level
after operation is advised as TURP syndrome may
of T10 is required for this. Sensory levels above T9
worsen later as fluid may continue to be absorbed.
should not be sought because the capsular sign (i.e.,
Monitoring of hemoglobin, sodium and osmolality has
pain on perforation of the prostatic capsule) would not
to be extended into the post-operative period.
be present should perforation occur.
Visual disturbance caused by glycine typically
Subarachnoid anesthesia is preferred generally
resolves fully within 24 hours and requires no treatment.
over continuous epidural anesthesia, because it is
Patient assurance is vital to allay anxiety.
technically easier to perform in elderly patients, the
6. What is the choice of anesthetic technique for duration of the surgery is generally not very long and
TURP? the incomplete block of sacral nerve roots that occa-
sionally occurs with the extradural technique is usually
Spinal anesthesia is regarded as the technique
avoided with subarachnoid anesthesia.
of choice for TURP. It offers several advantages over
general anesthesia. It provides adequate anesthesia Treatment of hypotension under spinal anesthe-
for the patient, good relaxation of the pelvic floor and sia should be with vasopressors rather than with fluid
the perineum for the surgeon; the signs and symptoms administration, to reduce the risk of fluid overload. For
of fluid overload can be recognized early because the patients with small glands, where the operative time
patient is awake; accidental bladder perforation is also will be less, combining local anesthetics with intrathecal
recognized easily if the spinal level is limited to T10 opioids like fentanyl helps in decreasing the incidence
because the patient would experience abdominal or of hypotension with subarachnoid block.
shoulder pain.
However, general anesthesia can be administered
The amount of operative blood loss is also lesser safely in patients with contraindications to spinal anes-
with regional anesthesia (RA). The decrease in blood thesia.
loss is due to the decrease in systemic blood pressure
Limited TURP in high-risk patients can be per-
secondary to the sympathetic blockade of RA and also
formed using local infiltration of the perineum and
due to the decreased peripheral venous pressure that
the prostatic fossa. However, the quality of operative
results in reduced bleeding from the prostatic venous
analgesia is inferior to a spinal anesthetic.
sinuses.
Routine intraoperative monitoring of ECG, blood
Another advantage of RA is that the sympathetic
pressure, oxygen saturation, end-tidal CO2 and tem-
block that it produces increases venous capacitance
perature is mandatory. High risk patients should have

invasive arterial and central venous pressures moni- If primary fibrinolysis is suspected, aminocaproic acid
tored, as indicated. may be effective when given intravenously in a dose of
4 – 5 g in the first hour, followed by 1g/h. Tranexamic
Antibiotics should be administered prior to instru-
acid 15 – 25 mg/kg may also reduce the volume of
mentation of the urinary tract, to prevent bacteremia.
hemorrhage.
The prostate harbors many bacteria, which can be a
source of intraoperative and postoperative bacteremia If bleeding becomes uncontrollable, the procedure
through the prostatic venous sinuses. This risk is further should be terminated as quickly as possible, and a
increased by the presence of an indwelling urinary Foley catheter should be passed into the bladder and
catheter. Manifestations of septicemia include fever, traction applied to it. The catheter’s inflated balloon
chills, tachycardia, hypotension and cardiovascular exerts lateral pressure on the prostatic bed and reduces
collapse. Intraoperative endotoxemia can occur even bleeding.
in patients with negative preoperative urine cultures
8. Why does hypothermia occur in TURP?
despite routine antibiotic prophylaxis.
Significant absorption of cold irrigating fluids
Administration of hypotonic intravenous fluids
(stored at room temperature) may lead to a decrease
should be avoided. 0.9% saline is preferred to Lactated
in the patient’s body temperature and cause shiver-
Ringer’s solution due its higher sodium content and
ing. The use of warm irrigating solutions can prevent
tonicity.
this. It has been shown that warming of fluids does
7. How is bleeding assessed during TURP? not increase bleeding through vasodilation. Forced
air warming devices can be used intraoperatively to
Hypertrophied prostate is highly vascular and
maintain normothermia, in addition to warming irrigation
operative bleeding during TURP can be significant. It
fluids.
is difficult to quantify blood loss during TURP due to
the large volume of irrigating solution used. The blood 9. How can perforation be recognized intraop-
loss is approximately 2 – 5 ml/min of resection time or eratively?
20 – 50 ml/g of resected prostate. These guidelines are
Bladder perforation during TURP can be second-
only rough estimates and the patient’s vital signs and
ary to overdistension with irrigation fluid or contact
serial hematocrit values should be monitored to assess
of the bladder wall with the surgeon’s resectoscope.
better the blood loss and the need for transfusion.
Signs and symptoms of bladder perforation include
Factors associated with excessive bleeding in- bradycardia, hypotension, restlessness, diaphoresis,
clude a large gland, extensive resection (> 40 – 60g nausea, abdominal pain, dyspnea, shoulder pain and
of prostate chippings), co-existing infection, prolonged hiccups. Extraperitoneal perforation may be manifested
surgery (> 1 h), and the presence of a preoperative as pain in the periumbilical, inguinal or suprapubic area.
urinary catheter. Intraperitoneal bladder perforation, a less frequent
event, may cause symptoms related to diaphragmatic
Because adrenergic receptors are abundant in
irritation (pain referred to the upper part of the abdo-
prostate tissue, the use of adrenergic agonists would
men, precordial area, shoulder region or neck).
cause vasoconstriction of prostatic blood vessels and
a decrease in blood loss. Regional anesthesia offers the advantage of a
conscious patient, so that bladder perforation can be
Abnormal bleeding after TURP occurs in less than
recognized early.
1% of cases. It is due to systemic fibrinolysis secondary
to plasmin, as the prostate releases tissue plasmino- 10. What are the postoperative problems?
gen activator that converts plasminogen into plasmin.
Postoperative pain is not usually severe, although
It could also be due to disseminated intravascular
discomfort from bladder spasm or from the urinary
coagulation triggered by the systemic absorption of re-
catheter may occur. Catheter pain may be treated
sected prostate tissue, which is rich in thromboplastin.
with lidocaine gel and bladder spasm can be treated
with muscarinic receptor antagonists (hyoscine bu- 2. Barash PG. Clinical Anesthesia. 6th edition. Lippincott,
tylbromide). Clot retention may occur after operation, Williams & Wilkins, 2009.
particularly if irrigation is inadequate and may lead to 3. Gravenstein D. Transurethral resection of the prostate
bladder overdistension, which is painful and may pre- (TURP) syndrome: A review of the pathophysiology and
cipitate severe bradycardia due to vagal stimulation. management. Anesth Analg 1997;84:438-46.
Mechanical measures such as flushing the bladder or
milking the catheter may be successful, but occasion- 4. O’Donnell AM and Foo I TH. Anaesthesia for transure-
ally the patient may need to be taken back to theatre thral resection of the prostate. CEACCP 2009;9(3):92-
for evacuation of a bladder hematoma. 96.
RECOMMENED READING 5. Mebust WK et al. Transurethral prostatectomy: imme-

diate and postoperative complications. A co-operative
1. Miller RD. Miller’s Anesthesia. 7th edition. Churchill
study of 13 participating institutions evaluating 3,885
Livingstone, 2010.
patients. J Urol 1989;141:243-7.

Neerja Bhardwaj
Bronchiectasis for lung resection 315 Mukul kapoor
01 BRONCHIECTASIS FOR LUNG RESECTION
Neerja Bhardwaj
Mukul kapoor
A 40 year old man came with complaints of cough or to surgery, an estimate of respiratory function
with expectoration, and breathlessness on mild exertion in all three areas–lung mechanics, parenchymal
for the past one year. He is a known case of pulmonary function and cardiopulmonary interaction–should
tuberculosis ten years back and was treated for it with be made. These includes spirometry – measuring
antituberculous drugs. He is a known smoker for the forced expiratory volume at first second (FEV1),
past 20 years. No other history of co-morbid illness. blood gas analysis, diffusing capacity of the lung
Effort tolerance - able to climb one flight of stair case for carbon monoxide (DLCO), maximal voluntary
ventilation, quantitative lung scan, quantitative
General examination revealed pallor and club-
computed tomography based on indication and
bing pulse rate-100/ minute, BP-100/60mmHg, RR-20/
cardiopulmonary exercise test. The following
minute, breath holding time 10 seconds. Weight 45Kg
figure shows the “3 legged stool” of preoperative
RS-Right infra axillary and infrascapular coarse creps
assessment.
(+), CVS-S1S2 heard.
Lab investigations: Hb-9 gms%, TC-12,000cells/mm3,
DC- P-50 %, L-40%, M-5%, E -3%, platelet count-
2,50,000 cells/mm3, serum creatinine - 0.9 mg/dl.
Chest X-ray - Honey comb opacities in the right lower
zone and haziness in the left mid and lower zones.
C.T thorax shows – Rt lower lobe fibrocalcific lesion
and bronchiectatic changes of Rt lower lobe with mul-
tiple cystic lucencies. Pulmonary function tests shows
marked restrictive pattern.
Discussion
• Further evaluation of this patient and optimisa-
tion
• Prediction of post operative pulmonary status 2. How will one optimise this patient preopera-
tively?
• Physiology of one lung ventilation
One can improve preoperative lung function by
• Various lung isolation techniques - merits and
the following methods:
demerits
• Cessation of smoking: The optimal timing
• Problems with DLT tube placement
for smoking cessation preoperatively is un-
• Ventilator strategies known but it should be stopped as early as
possible.
• Post op analgesia and intensive care
• Improvement of nutrition to prevent increase
Question and answer
in need for postoperative ventilation and
1. How will you evaluate this patient further? length of hospital stay.
The best assessment of respiratory function is by • Physical therapy is standard intervention
knowing the patient’s level of physical activity. Pri- for improving preoperative respiratory func-
Neerja Bhardwaj
tion. These include incentive spirometry and is a predictor of average risk for complications.
breathing exercises. Similarly, a postoperative DLCO value of 40% is
currently used to distinguish between normal and
• Medical therapy consisting of inhaled bron-
higher risk lung resection patients. However, the
chodilators, beta-2-agonists, anticholinergics
recent ERS/ESTS guidelines suggest that both
and if needed antibiotics.
limits should be lowered to 30%. If calculation of
3. How can one predict postoperative pulmonary the postoperative lung function shows borderline
status? values, the patients should perform a cardiopul-
If the patient has a FEV1 value after a broncho- monary exercise test. The exercise test is used
dilator of less than 2 litres or less than 50% of to stress the entire cardiopulmonary and oxygen
the predicted value then he is at risk when a delivery system in order to assess the functional
pneumonectomy is planned. Similarly, a 60% reserve that can be expected after pulmonary
predicted value of the diffusing capacity of the lung resection. Exercise capacity, expressed as the
for carbon monoxide (DLCO) or a 50% predicted maximal oxygen uptake (VO2 max) is lower in
value of maximal voluntary ventilation (MVV), is patients who develop clinically relevant complica-
risky if the patient has to undergo pneumonec- tions after lung resection. Patients with a preop-
tomy. If the patient is scheduled for lobectomy, erative V˙O2 max greater than 20 ml/kg/min are
FEV1 value greater than 1.5 litres, corresponding not at increased risk for complications or death.
approximately to 60% of the predicted value, is While patients with a preoperative V˙O2 max
considered as a well tolerated lower limit. A blood lower than 10 ml/kg/min show a very high risk for
gas analysis is indicated in this patient since postoperative complications or death. Moreover,
he has dyspnea on mild exertion and produc- a preoperative V˙O2 max lower than 15 ml/ kg/
tive cough. Preoperative hypoxemia with arterial min indicates an increased risk of perioperative
oxygen saturation (SaO2) less than 90% has been complications. In older people, short people, and/
associated with an increased risk of postopera- or female patients who may have normal predicted
tive complications. An arterial partial pressure of absolute values below 15 ml/kg/min, the V˙O2 max
carbon dioxide (PaCO2) value greater than 45 may be expressed as percentage of the predicted
mm Hg, is not considered as an independent risk value and the threshold of V˙O2 max for surgical
factor for increased perioperative complications. intervention can be set between 50% and 60%
In addition to estimate the likely post resection pul- of predicted without excess surgical mortality.
monary reserve a quantitative lung scan, using 4. Explain in short the physiology of one lung
either inhaled radioactive xenon gas for ventilation ventilation?
or 99mTechnetium macroaggregated albumin for
When the patient is in the upright position, both
assessing blood flow may be required. This allows
ventilation and perfusion are greater in the more
the calculation of the functional remaining paren-
dependent versus the less dependent portions of
chyma after surgery and the predicted post resec-
the lungs. However, the gravitational gradient of
tion FEV1 value. However, the estimates are less
blood flow exceeds the gradient of ventilation, re-
precise for patients who will undergo lobectomy
sulting in a spectrum of ventilation perfusion ratios
compared with pneumonectomy. Quantitative
(V/Q). In the normal lungs, this ratio varies from
computed tomography provides comparable
0.6 at the bases to 3.3 at the apices, with a mean
results to those obtained by perfusion lung scan-
value of 0.8. Thoracic surgery usually requires
ning in predicting postoperative lung function and
unilateral lung deflation and placing the patient in
is also a reliable tool to predict post resection lung
a lateral decubitus position. In a spontaneously
function, in patients undergoing a lobectomy. An
breathing patient, the dependent hemidiaphragm
estimated postoperative FEV1 greater than 40%
undergoes greater excursion (doming effect)

Neerja Bhardwaj
than the nondependent hemidiaphragm does, is a decrease in blood flow to the nondependent
favoring ventilation of the dependent lung. The lung. The primary mechanism for the redirection
induction of anesthesia and muscle paralysis do of blood flow is hypoxic pulmonary vasoconstric-
not cause a significant change in the distribution tion (HPV). Without HPV, severe hypoxia will
of blood flow but have an important impact on the result from SLV. The phenomenon of HPV starts
distribution of ventilation and cause a significant immediately and both alveolar carbon dioxide
decrease in functional residual capacity (FRC). tension and the blood pH level modulate the
Muscle paralysis and intermittent positive pres- HPV response. While hypocapnia and alkalosis
sure ventilation abolish the doming effect and decrease HPV and cause vasodilatation, hy-
increase the nondependent lung ventilation. Also, percapnia and metabolic acidosis enhance the
ventilation to the dependent lung is impeded by vasoconstrictor response. Mixed venous oxygen
the compression of the dependent hemithorax by tension (PvO2) also modifies the extent of HPV.
the mediastinum and abdominal contents. High PvO2 decreases HPV, low PvO2 mildly in-
creases HPV, and HPV is maximal when alveolar
The initiation of SLV causes considerable change
PO2 is approximately 20 to 40 mm Hg.
in the distribution of ventilation and perfusion.
Ventilation of the dependent lung is increased, 5. What are various lung isolation techniques
while ventilation of the nondependent lung ceas- available for use? What are their advantages
es. and disadvantages?
On initiation of SLV with an inspired oxygen frac- The current options for one lung ventilation include
tion (FiO2) of 1.0, the partial pressure of oxygen double lumen tubes and bronchial blockers.
(PaO2) values drops from approximately 400 mm
• Double lumen tubes: are polyvinyl chloride tubes
Hg to a nadir of 200 mm Hg at 20 to 30 minutes.
which are disposable with high volume, low pres-
The major cause of this hypoxemia is the pulmo-
sure cuff, a fixed curvature, without carinal hook
nary arteriovenous shunt of the deoxygenated
and a colored (blue) bronchial cuff with difference
blood through the upper nonventilated lung. With
in design for left/right. Available in sizes 26 F, 28
the initiation of SLV and consequent nondepen-
F, 32 F, 35 F, 37 F, 39 F, 41 F.
dent lung atelectasis and alveolar hypoxia, there
• Bronchial blocker: Available as Univent tube and
Arndt blocker.
The table below compares the above tubes keeping in mind their advantages and disadvantages.
Double lumen tube Bronchial blocker

Advantages
Large lumen facilitates suctioning Easy recognition of anatomy
Best device for absolute lung separation Best device for patients with
difficult airway
Conversion from 2 to 1 lung ventilation No cuff damage during
easy and reliable intubation
Disadvantages
Difficulty in selecting proper size Small channel for suction
Difficult to place during laryngoscopy Problematic to convert from 1 to
2 then to 1 lung ventilation
Damage to tracheal cuff High maintenance device –
possibility of dislodgement or
loss of seal
Major tracheobronchial injuries

Neerja Bhardwaj
6. Innumerate the problems with DLT place- 7. Which ventilator strategies are available for
ment? use in OLV?
The various problems which can occur during During OLV FiO2 of 1.0 is used to avoid hypoxemia.
placement of DLT are: malpositioning, require- Insufflation of oxygen into a selective bronchus,
ment of multiple tube changes, prolonged periods application of PEEP to dependent lung, CPAP to
of hypoxia/hypoventilation, lung trauma and lung the non-dependent lung are some of the ventila-
contamination. The various malpositions which tory strategies used. Intermittent nondependent
can occur include – tube accidently enters to the lung ventilation using small tidal volumes, and
side opposite the desired main stem bronchus, high-frequency jet ventilation or high-frequency
DLT may be passed too far down into the right percussive ventilation is successful in treating
or left side bronchus or it may not be inserted far hypoxemia during one-lung ventilation without
enough and a right sided DLT may obstruct the impeding surgical exposure. The following table
right upper lobe orifice. All these can be taken care gives guidelines for ventilatory management of a
of using FOB to confirm the site of placement. patient undergoing OLV.
8. What monitoring techniques are required dur- including dizziness, nausea, and vomiting, as well
ing major thoracic surgery? as dose-dependent sedation and respiratory de-
pression. The non-opioids commonly used include
NSAIDs and acetoaminophen. They are useful
only as a supplement to epidural anesthesia and
to decrease opioid demand. They can lead to
inhibition of platelet function, fluid retention and
dyspepsia.
Intravenous patient-controlled analgesia
(PCA) is a technique that allows the patient to
self-administer small intravenous boluses of an-
algesics like potent opioids at frequent intervals
using a special PCA pump. However the side
9. What are the various options for postoperative
effects of opioids remain the same.
analgesia?
Thoracic epidural analgesia - is a preferred
Thoracotomy is a very painful procedure and
analgesic technique in thoracic surgery. It reduces
requires pain management to prevent respiratory
intraoperative anesthetic and analgesic require-
complications and to perform intense physical
ments and provides efficient post-thoracotomy
exercises. The various options available are:
pain control. Local anesthetic agents and opioids
Systemic analgesics – opioids and non-opioids are most commonly applied through an epidural
can be administered via IV and IM routes. The catheter. It has been shown that the combina-
opioids generally used include morphine, fentanyl tion of both substances provides the possibility
and pethidine. Opioids may cause side-effects, of reducing the respective concentrations and is

Neerja Bhardwaj
superior to the sole application of opioids, particu-

larly for analgesia during mobilization. In contrast
to the lipophilic opioids, fentanyl, sufentanil, and
alfentanil, which are more rapidly absorbed from
the CSF, hydrophilic opioids such as morphine
remain in the CSF for a longer time. After single
injections this may have the advantage of a longer
duration of analgesia, but also carries a higher
potential risk of delayed respiratory depression
as a result of rostral spread. The thoracic route
of administration is superior to the lumbar route in
view of analgesia, lower limb weakness and car- References
dioprotective effects of the sympatholysis when
1. Slinger P. Update on anesthetic management for pneu-
local anesthetic agents and lipophilic opioids are
monectomy. Curr Opin Anesthesiol 2009; 22: 31 – 7.
administered.
2. Chetta A, Tzani P, Marangio E, Carbognani P, Bobbio
Interpleural analgesia – its benefit in thoracic
A, Olivieri D. Respiratory effects of surgery and pul-
surgery is controversial. The problems associated
monary function testing in the preoperative evaluation.
with its use include loss of analgesia because
Acta Biomed 2006; 77; 69-74.
of local anesthetic getting removed via drains,
systemic toxicity because of high concentration 3. Behr J. Optimizing preoperative lung function. Curr
of local anesthetics and no improvement of post- Opin Anesthesiol 2001; 14: 65 – 9.
surgery lung function. 4. Azad SC. Perioperative pain management in patients
Extrapleural paravertebral analgesia – provides undergoing thoracic surgery. Curr Opin Anesthesiol
good pain relief and preservation of pulmonary 2001; 14: 87 – 91.
function. Important side-effects such as hypoten- 5. Cohen E. Management of one lung ventilation. Anes-
sion, urinary retention, nausea, and vomiting ap- thesiol Clin N Am 2001; 19: 475 – 95.
pear to be less frequent with paravertebral block
6. Tzani P, Chetta A, Olivieri D. Patient assessment and
than with thoracic epidural analgesia.
prevention of pulmonary side-effects in surgery. Curr
10. How does one predict whether patient will Opin Anesthesiol 2011; 24: 2 – 7.
require mechanical ventilation postopera-
7. Ishikawaa S, Lohsera J. One-lung ventilation and
tively?
arterial oxygenation. Curr Opin Anesthesiol 2011; 24:
24 – 31.

Brief Overview of Inhalation and Intravenous Neerja Bhardwaj,
Induction of Anesthesia in Children 320 Anju Grewal
BRIEF OVERVIEW OF INHALATION AND INTRAVENOUS
INDUCTION OF ANESTHESIA IN CHILDREN
Neerja Bhardwaj
Anju Grewal
Introduction Inhalational mask induction techniques in older

pediatric patients:
There are a variety of techniques for inducing
general anesthesia. Pediatric anesthesiologists need 2. “Steal induction” technique: It is used if the
to make a choice between two recommended methods: child is already asleep on arrival in the operating room
inhalational or intravenous. We have briefly summa- and aims at not disturbing the child any further. This
rized the salient points of inhalation and intravenous atraumatic technique involves priming the circuit with
induction techniques and agents used in children and N2O in O2, and gradually bringing the mask gently near
tabulated the advantages and disadvantages together the child’s face until it is tightly applied to the face.
for quick review by the postgraduate student: Sevoflurane or halothane is introduced in increas-
Inhalational Induction ing concentrations after the child has been breathing
N2O for 1 to 2 minutes. Adequate monitoring must be
Inhalational anesthesia is the most common
instituted as soon as possible, and the child is then
method of inducing anesthesia in children as inhala-
transferred to the operating table. However, if the
tional anesthetics are effective, reliable, safe, easy to
deliver, stable and without major end-organ sequelae. child suddenly awakens during the induction it can be
Psychologically atraumatic induction of anesthesia also severely traumatic psychologically to the child.(2,4)
requires excellent communication skills on the part of 3. The single-breath induction is especially appeal-
the anesthesiologists seeking cooperation from the ing to children who desire to fall sleep “really fast”
child.1 While inhalational mask induction can be used with a face mask but requires a very cooperative child
easily in infants younger than 10 to 12 months, it may who can follow instructions. Thus it works best with
pose problems in an older child, where a good premedi- older children, although some cooperative 3 year old
cation has an important role for successful atraumatic can also be anesthetized with this technique. Before
induction. The major barrier in inhalation induction is beginning, the anesthesiologist should demonstrate
fear of mask experienced by nearly all ages. This can
using an unattached face mask and the child should be
be overcome to great extent by employing differing
coached through a mock induction on how to “breathe
techniques as per the age, degree of sedation and
in the biggest breath possible” and then “breathe out
cooperative abilities of the child.(1,2,3)
completely.” Before induction, the circuit and reservoir
Inhalational mask induction techniques in Infants bag are primed with 70% N2O in O2 and the maximum
1. Hand or finger technique: Few children or in- concentration of concentration of halothane or sevo-
fants would not allow mask anywhere near them for flurane that is possible. This is achieved by running
various reasons or fears. These children or infants can modest fresh gas flows through the circuit and inter-
be anesthetized by placing the elbow of the breathing mittently emptying the reservoir bag manually into
circuit between the anesthesiologist’s fingers, and then the scavenger system (i.e., with the circuit occluded).
cupping one’s hands below the chin. The cupped hands Once the circuit is primed with inhalation agent at high
act as a reservoir and gently cover the mouth. Nitrous concentration, the distal end of the circuit is occluded
oxide followed by sevoflurane can be added gradually. (to avoid contaminating the operating room) and the
Alternatively the little finger can be used to soothe the child is instructed to take a deep breath of room air
child by placing it in the mouth of young infants and the and to exhale all the air and hold expiration. The face
face mask is then gently advanced to their nose and mask is then placed securely over the child’s mouth
mouth.(2,4) and nose while he or she is instructed to take in the

“deepest breath ever” and “hold it, now just breathe dence of bradycardia, hypotension, and arrhythmias is
normally.” Loss of consciousness, as noted by loss of reported with halothane. Hence sevoflurane has largely
the eyelash reflex, results soon after this vital capacity replaced halothane by sevoflurane for inhalation induc-
breath (2,4) tion of anesthesia. However apnea and arrthymias may
occur after a sevoflurane induction, particularly if a
4. Distraction & or restraint technique: Used when
large concentration is administered after a midazolam
the child is reluctant to lie on the operating table but
premedication. Manual ventilation for a brief period
has ability to follow instructions. In this technique the
and if necessary, reducing the inspired sevoflurane
child is allowed to sit in the lap of his/her parents or
concentration, are usually all that is required to main-
anesthesiologists and then use either gentle restraint
tain anesthesia and facilitate return of spontaneous
and distraction in form of blowing balloons or making
respiration.(1,2)
mountains on the monitor (EtCO2 curves) or any other
distracters like soft toys etc along with primed scented Movement has been reported during sevoflurane
mask and circuit are applied gently till the child loses anesthesia when i.v. access was attempted , it is im-
consciousness. It is also important to have an experi- perative to maintain a large inspired concentration of
enced individual in front of the child and parent to hold sevoflurane (and continue 70%nitrous oxide) early dur-
onto the child as induction proceeds and help place ing the induction and to be patient before establishing
the child on the operating room table after successful i.v. access.(1,2)
induction.
In contrast to halothane, sevoflurane does not
Hypnosis has also been used successfully to increase the myocardial sensitivity to epinephrine.2,4
distract children. Hypnosis is an altered state of con- Halothane sensitizes the heart to catecholamines, and
sciousness with highly focused attention, based on the ventricular arrhythmias may commonly be seen, espe-
principle of dissociation.[336] Age appropriate scenarios cially during periods of hypercapnia or light anesthesia.
and fantasy stories can be used to produce a state of However if bigeminy or short bursts of ventricular
hypnosis which absorbs children in a state of inner ab- tachycardia occur, then either of the following can be
sorption and reduced awareness of immediate physical employed: (1) hyperventilation (to reduce the PaCO2)
surroundings and experiences. (2,4) (2) deepening of the halothane anesthesia, or (3)
change to an alternate potent inhalation agent.2,5 There
Comparative characteristics of inhalation induction
is no role for intravenous lidocaine to treat these ar-
with sevoflurane vs halothane vs desflurane
rhythmias.(2,6,7)
Five inhalational anesthetics are available for use
A decreased time to loss of the eyelash reflex
today in children: sevoflurane, isoflurane, desflurane,
and a decreased incidence of excitement during the
halothane, and nitrous oxide. The current ether anes-
induction was observed when nitrous oxide was added
thetics have limited cardiorespiratory depression, no
to the breathing mixture in a 1:1 ratio with oxygen.(2)
neurotoxicity and minimal risk for hepatorenal toxicity.
Spontaneous respiration is easy to maintain with an Agitation or excitement in early induction (shortly
inhalational anesthetic; the decrease in tidal volume is after loss of eyelash reflex) with sevoflurane has
offset by an increase in respiratory rate. Ether anesthet- been observed. In addition, minor seizure-like activity
ics depress the circulation in a dose-dependent manner characterized by muscular rigidity and uncoordinated
that is easily reversible by decreasing the anesthetic movements of arms and legs occasionally occurs.2,8,9
concentration, and/or administering atropine and fluids. This emergence agitation is self-limiting (10-20 min
(2)
duration) and occurs mainly in preschool children. A
small dose of propofol, opioid, dexmedetomidine, or
Sevoflurane is the most commonly used agent
clonidine may be administered to prevent emergence
for inhalation induction as it is safe, with incremental
delirium. No long-lasting neurologic or electroencepha-
dosing, rapid in onset. Small increases in heart rate
lographic sequelae due to the use of sevoflurane in
are observed with sevoflurane whereas a greater inci-

children have been reported. The odds ratio for sevo- Nearly all intravenous anesthetic agents have
flurane compared to halothane is 2.2. (1,2) A recent meta been used with specific concerns for use of propofol
analysis revealed that all intravenous agents show a in neonates. Clinically, in healthy patients older than
lower incidence of postoperative emergence agitation, six months, satisfactory anesthesia can be obtained by
and that midazolam premedication does not prevent infusing propofol and co-administering opioids: a bolus
it.(10) dose of propofol is followed by a continuous infusion
of 13 mg/kg/h for 10 min, then 11 mg/kg/h for 10 min
Desflurane and also isoflurane is very pungent
then 9 mg/kg/h thereafter.
and causes significant airway irritation, with inhalation
induction attempts resulting in severe laryngospasm Compared to manual control, computer-controlled
(49%), coughing, increased secretions, breath-holding syringe drivers allow TCI and facilitate the drug ad-
and hypoxemia.2,8 Hence, desflurane is not recom- ministration, but they are not yet widely available for
mended for inhalation induction in children but may children. In addition to the evaluation of the clinical
be used safely for maintenance of general anesthesia signs, cerebral pharmacodynamic feedback, such
when the trachea has been intubated.(2) as BIS, may be especially useful as the predictability
of plasma propofol concentrations with the classical
Intravenous induction
pharmacokinetic models is limited in children.(1-4)
Intravenous induction is usually reserved for older
Thus propofol anesthesia offers advantages of
children, those who request an intravenous induction,
rapid onset, better preservation of spontaneous breath-
those with a previously established intravenous cath-
ing, lower incidence of laryngospasm, less need for
eter, those with potential cardiovascular instability, and
airway manipulations and more importantly a rapid and
those who need a rapid-sequence induction because
peaceful emergence with no postoperative vomiting
of a full stomach.
Table 4-9 Doses & Characteristics of Commonly Used Intravenous Induction Agents (2,4)
Adverse Special use /
Drug Dose Pharmacokinetics
effects Advantages
Thiopental 5.0-8.0 mg/kg The beta-elimination half-
neonates need a life of thiopental in
smaller dose neonates is twice that in
3 to 4 mg/kg their mothers (15 vs. 7
hours), so a single dose
may produce excessively
long effects in neonates
Methohexital 1.0-2.5 mg/kg Larger doses Infrequently used
cause skeletal
muscle
hyperactivity &
myoclonic
movements.
Pain at the
injection site is
common
Also associated
with hiccups
Propofol 2.5-3.5 mg/kg The early distribution half- Pain on However, in
life is about 2 minutes, injection - can general, at a given
Induction dose and the elimination half- be minimized plasma
life is about 30 minutes by use of concentration, the


effects Advantages
varies with age lidocaine (0.5 to hypnotic effects are
Clearance is very large 1.0 mg/kg) rapidly
In children, higher doses (2.3 ± 0.6 L/min) and while applying obtained; and much
of propofol are required exceeds liver blood flow tourniquet faster deepening of
mainly because of pressure anesthesia
increased distribution proximal to the is possible with
from plasma to peripheral injection site for propofol compared
compartments. Due to its relatively low 30 to 60 with an inhalational
context-sensitive half- seconds before agent
time, it can be used as an injecting the
infusion in TIVA. propofol Lower incidence of
airway-related
Propofol infusions < 4mg/ Propofol has problems (e.g.,
Kg/Hr, for less than 48 been laryngospasm),
hours considered safe associated with more rapid
cardiac arrest emergence, and a
However long term in children lower incidence of
infusion need to avoided during nausea & vomiting
due to development of two notable
PRIS scenarios: useful for pediatric
prolonged patients undergoing
In neonates and in infusions in nonoperating room
younger infants, propofol infants and procedures such as
clearance children in computed
is decreased because of intensive care tomography (CT),
immaturity of the hepatic unit (ICU) and MRI, radiotherapy,
enzyme system. in neonates at bone marrow
induction of biopsy, upper and
anesthesia. lower
gastrointestinal
endoscopy, and
The context-sensitive lumbar puncture.
half-life increases more in Use of
children, so that rapid continuous or Rapid and peaceful
awakening is not a repeated recovery
predominant feature of intermittent
TIVA in children administration
of propofol in
the first weeks
of life is not
recommended
in neonates
Etomidate 0.2-0.3 mg/kg Myoclonic provides marked
movements are cardiovascular
associated with stability
etomidate
administration; Useful in children
this agent can with
suppress cardiomyopathy or
adrenal steroid those who are
synthesis,and it hypovolemic after
causes pain on trauma
injection.


effects Advantages
Ketamine 1.0-2.0 mg/kg Ketamine is a useful induction

Dose should be myocardial agent for children
reduced in cases depressant that with cardiovascular
of severe can result in instability,
hypovolemia systemic especially in
hypotension in hypovolemic states,
children who or for those who
already are cannot tolerate a
maximally reduction in
compensating systemic vascular
with resistance, such as
endogenous those with aortic
catecholamines stenosis or
congenital heart
disease in whom
the balance
between pulmonary
and systemic blood
flow is vital for
maintaining
cardiovascular
homeostasis.
Ketamine is
associated with
increased
oropharyngeal
secretions,
psychomimetic side
effects
(hallucinations,
nightmares), and
postoperative
nausea and
vomiting.
administration of an
antisialagogue and
midazolam is
recommended to
attenuate these
side effects.

COMPARISON OF ADVANTAGES AND DISADVANTAGES OF INHALATION VS INTRAVENOUS

INDUCTION(1-4)
S.No. INHALATION INDUCTION INTRAVENOUS INDUCTION

1 Can be used in all children, however more Can be used in all age groups especially if a
useful in small children. previously established intravenous catheter is present,
Inhalational anesthetics are the primary in those with potential cardiovascular instability, and
induction agents for children with normal those who need a rapid-sequence induction because
and difficult airways, foreign body in the of a full stomach.
airway, epiglottitis, an anterior mediastinal Other indications of intravenous induction include
mass and asthma epilepsy, malignant hyperthermia, child posted for
neurosurgical procedures with high risk of cerebral
ischemia
Can be used in peripheral locations, it is independent
from airway instrumentation
Though intravenous induction has been the mainstay for rapid sequence induction, however infants
with pyloric stenosis are anesthetized by inhalational anesthesia without adverse outcomes.
2 Only a few absolute contraindications Use of propofol in small neonates in the first few
exist, for e.g., malignant hyperthermia, weeks of life is contraindicated. Similarly prolonged
muscular dystrophy, Wernig–Hoffman infusions of propofol are not recommended for the
disease and the absence of appropriate fear of development of PRIS (Propofol infusion
delivery systems syndrome).
Induction of anesthesia in children with PRIS has been reported after short-term sedation and
right to left shunts may be slower, hence after anesthetics of 2½ and 6 h duration in children
not the method of choice
3 Potent inhalational anesthetics satisfy all In contrast, intravenous anesthetic agents
four pillars to varying degrees. They such as propofol induce anesthesia, may cause
induce loss of consciousness (with limited amnesia, partially blunt autonomic reflex responses
response to pain), confer amnesia, blunt and do not potentiate muscle relaxants
reflex responses, and potentiate Ketamine has an added advantage of an excellent
muscle relaxants. analgesic
The four pillars of general anesthesia are loss of consciousness ś amnesia, analgesia, ablation or
blunting of autonomic reflex responses, and muscle relaxation.
4 Painless and smooth induction of Rapid and smooth loss of consciousness with rapid
anesthesia emergence. Rapid onset of action independent from
the alveolar ventilation.
At a given plasma concentration, the hypnotic effects
are rapidly obtained and much faster deepening of
anesthesia is possible with propofol compared with an
inhalational agent
Pain on injection of propofol can be alleviated by
addition of lidocaine.
5 I.V access can be secured after induction I.V. access needed prior to induction, which can be
Avoids psychological trauma of needles, fearful and painful
however fear of masks does occur Needle pain can be minimized by use of EMLA, LAT
Movement has been reported during gel, Ametop cream
sevoflurane anesthesia when i.v. access
was attempted. This is attributed to the
reduced solubility of sevoflurane in blood
resulting in decreased speed of induction
of anesthesia with sevoflurane than with
halothane
However the key to avoid phobia & fears and achieve smooth induction of anesthesia is
use of good premedication, distracters & positive contributions from parents/ clowns etc

6 Requires provider skills to manage the Needs provider skills in IV cannulation & bag and
airway with a bag and mask mask ventilation
7 Apnea and arrythmias may occur after a Can be titrated in small increments to maintain stable
sevoflurane induction, particularly if a hemodynamic profile.
large concentration is administered Sudden hypotension, bradycardia, apnea can occur,
after a midazolam premedication. but can be avoided by careful titration
8 Better safety margin in marginal / difficult Careful titration needed so that apnea does not occur
airway and spontaneous respiration is maintained
Rapid emergence can be life saving if the
airway becomes difficult to manage with a
bag and mask
9 Desflurane and isoflurane have been Propofol has been found to be less irritating to the
associated with higher incidence of airway airways and results in a decreased incidence of
irritability (due to its pungent odor), laryngospasm
breath-holding, coughing, excessive Propofol compromises airway patency and respiration
salivation and laryngospasm in children and may cause transient apnea. If airway
Sevoflurane and Halothane produce less obstruction/apnea occurs, the chin lift maneuver
airway irritability and better conditions for augments the patency of the upper airway & BMV
laryngeal mask airway insertion maintains oxygenation
10 Dosing of inhalational agents is simple: by Dosing regimens for propofol are variable in children,
measuring the end tidal concentrations as with very large inter-individual blood concentrations of
an estimate of the blood concentrations, propofol, three to fivefold greater than for inhalational
the pharmacokinetic process can be anesthetics
followed breath by breath in each
individual patient
11 Steady-state measures of potency can be Actual blood and brain concentrations of propofol (or
measured during inhalational anesthesia any other drug) cannot be accurately measured in real
by measuring the end-tidal partial time noninvasively
pressure of the anesthetic (an indirect
measure of the brain partial pressure of Monitoring the hypnotic state by adding
the anesthetic) EEG-based monitors will probably soon become
standard in pediatric anesthesia practice
Hence, agent analyzers can estimate the
depth of anesthesia during inhalational
anesthesia
12 Depth of anesthesia monitors do not Depth of anesthesia monitor required, as awareness
function well in young children and may occur twice as frequently as during inhalational
especially during sevoflurane anesthesia anesthesia
13 Agent analysers are more user friendly Less familiarity with target-controlled infusion (TCI)
systems and EEG-based hypnotic monitoring
14 As maximum deliverable concentrations Such agent analysis is not commercially available for
from the vaporizer and breath by- i.v. drugs. Hence we cannot be warned by any alarms
breath measurement of the inspired and about underdosage or overdosage of intravenous
expired inhalational concentrations, can agents immediately.
be monitored, a safety net is available Furthermore, no mechanism available to detect a
during inhalational induction disconnection in the i.v. line or s.c. infiltration of
intravenous agents
15. Seizures: Sevoflurane induction using Methohexital & etomidate have been associated with
higher concentrations >5 vol% have been excitatory myoclonic movements. However
found to be associated with epileptiform thiopentone and propofol have been associated with
EEG activity in young children which was smooth and rapid induction with no excitatory or
exaggerated in association with seizure like activity
hyperventilation

16 Recovery after both brief and prolonged Recovery after brief anesthesia with TIVA may be as
inhalational anesthetics is rapid rapid , whereas recovery after prolonged anesthesia
with TIVA is likely much more protracted
17 Potential for emergence delirium exists Improved quality of emergence from anesthesia.
more so with sevoflurane and desflurane Potential for emergence agitation is minimal
Excitation during induction can occur in Intravenous and rectal inductions are less distressing
bigger children to children than inhalational induction.
Though self limiting, it is more common
with sevoflurane. Studies have observed
an increase in behavioral changes in
postoperative period such as fear of dark,
difficulty in getting the child to bed, desire
of sleeping with parents in children when
sevoflurane was used as an induction
agent.11,12
Higher levels of anxiety during intravenous induction but greater behavioral disturbances in the
inhalational group have been reported in a study by Aguilera et al.13
Even in pain-free patients, postoperative agitation is common in preschool children after
sevoflurane, desflurane, and isoflurane anesthesia. The most evident option to prevent
postoperative agitation is to avoid inhalational agents for maintenance. Use of propofol for
maintenance increases the child’s comfort, and parental satisfaction(14,15)
18 Postoperative nausea and vomiting occur Propofol has antiemetic activities even at very low
with a background rate of about 20% after doses and has been found to be effective in
inhalational anesthesia preventing vomiting early after surgery Thus
intravenous anesthesia is the recommended
technique for tonsillectomy and squint surgery
Vomiting is a major cause of postoperative discomfort in children above the age of 2-3 years and
rated by parents as the most relevant outcome criteria. It is also one of the main reason for
admission after outpatient surgery . Avoiding inhalational agents is considered to be one of several
options, or even the primary option for preventing postoperative vomiting. (16)
19 Inhalational anesthetic agents are not Propofol anesthesia is best suited for MRI or CT
best suited for anesthesia in remote scans and for radiotherapy due to ease of
locations due to the need for airway administration, avoidance of airway instrumentation
manipulations and high incidence of due to preservation of spontaneous breathing,
emergence agitation minimal side effects and rapid recovery
20 Evoked potentials are suppressed or even Propofol does not suppress evoked potentials,
abolished by inhalational agents. reduces brain metabolism and cerebral blood flow,
Inhalational agents are thus not an ideal thereby allowing for an easier control of raised
agent for neurosurgical procedures intracranial pressure. Hence it is better suited for
neurosurgical procedures and spinal cord monitoring
during such procedures
21 Inhalational agents cannot be Intravenous anesthesia is the method of choice for
administered during transtracheal jet rigid or flexible bronchoscopy.
ventilation.
22 Can have environmental impact of No concerns regarding workplace contamination as it
depleting the ozone layer which is mainly is a nonpollutant to the theatre environment.
attributed to nitrous oxide
CONCLUSION
Each form of induction can be used based on the Ideally if no contraindications exist, then an
patient’s age, underlying medical condition, especially inhalation induction with Sevoflurane followed by
presence or absence of malignant hyperthermia etc maintenance with intravenous agents like propofol
and requirements of the type of surgical procedure. would be most suitable for brief procedures. However

for most prolonged surgeries, a low flow desflurane 7. Navarro R, Weiskopf RB, Moore MA, et al: Humans
maintenance would be a better choice as PRIS remains anesthetized with sevoflurane or isoflurane have simi-
a theoretical risk during prolonged administration of lar arrhythmic response to epinephrine. Anesthesiol-
propofol, Infusion pumps and BIS (though not reliable) ogy 1994; 80:545
would be needed to assure amnesia, and the cost per 8. Zwass MS, Fisher DM, Welborn LG, et al: Induction
kg after several hours increases for intravenous anes- and maintenance characteristics of anesthesia with
thesia in comparison to inhalational anesthetics.1,3 desflurane and nitrous oxide in infants and children. An-
A good preoperative preparation, premedication, esthesiology 1992; 76:373-378
availability of airway equipment and adequate peri- 9. Butler LD, Symons BK, Henderson SL, et al: Hypnosis
operative monitoring is essential for safe and smooth reduces distress and duration of an invasive medical
administration of either or a combination of anesthesia procedure for children. Pediatrics 2005; 115:e77-
strategies. Thus a judicious combination of the two e85.
methods can be used to minimize complications of both
in context to patient characteristics, type of procedures 10. Dahmani S, Stany I, Brasher C et al. Pharmacologi-
among children of all age groups. cal prevention of sevoflurane- and desflurane-related
emergence agitation in children: a meta-analysis of
REFERENCES published studies. Br J Anaesth 2010; 104: 216–223.
1. Lerman J, Jo¨ hr M. Pro-con Debate. Inhalational anes- Epub 2010 Jan 3.
thesia vs total intravenous anesthesia (TIVA) for pedi-
11. Watson A, Visram A. Children’s preoperative anxiety
atric anesthesia. Pediatr Anesth 2009; 19: 521–534.
and postoperative behaviour. Pediatr Anaesth 2003;
2. Ghazal EA, Mason LJ , Coté CJ. Preoperative Evalu- 13: 188–204.
ation, Premedication, and Induction of Anesthesia.
12. Bal N, Saricaoglu F, Uzun S et al. Perioperative anxiety
In: A Practice of Anesthesia for Infants and Children
and postoperative behaviouraldisturbances in children:
. Coté CJ, Lerman J, Todres ID editors. Philadelphia,
comparison between induction techniques. Eur J An-
Saunders. 2009 :36-60
aesthesiol 2006; 23: 470–475
3. Marzena Zielinska, Helen Holtby, Andrew Wolf. Pro–
13. Aguilera I, Patel D, Meakin G et al. Perioperative
con debate: intravenous vs inhalation induction of
anxiety and postoperative behavioural disturbances in
anesthesia in children. Pediatric Anesthesia 2011;
children undergoing intravenous or inhalation induction
21(2):159-168.
of anesthesia. Pediatr Anaesth 2003;13: 501–507.
4. Charles J. Coté. Pediatric Anesthesia. In: Ronald D.
14. Bortone L, Ingelmo P, Grossi S et al. Emergence agita-
Miller, Lars I. Eriksson, Lee A. Fleisher, , Jeanine P.
tion in preschool children: double-blind, randomized,
Wiener-Kronish, and William L. Young editors. Miller’s
controlled trial comparing sevoflurane and isoflurane
Anesthesia, 7th Edition:USA: Churchill Livinstone El-
anesthesia. Paediatr Anaesth 2006; 16: 1138–1143.
sevier; 2010:2565-77.
15. Uezono S, Goto T, Terui K et al. Emergence agitation
5. Rolf N, Cote CJ: Persistent cardiac arrhythmias in
after sevoflurane versus propofol in pediatric patients.
pediatric patients: effects of age, expired carbon diox-
Anesth Analg 2000; 91: 563–566.
ide values, depth of anesthesia, and airway manage-
ment. Anesth Analg 1991; 73:720-724 16. Gan TJ, Meyer TA, Apfel CC et al. Society for am-
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6. Johnston RR, Eger II EI, Wilson C: A comparative in-
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halothane in man. Anesth Analg 1976; 55:709-712.

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Physiology of neuromuscular transmission 1 Anitha Shenoy

BASIC SCIENCE LECTURES

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

01 PHYSIOLOGY OF NEUROMUSCULAR TRANSMISSION

Professor Anitha Shenoy

Introduction Acetyl choline released from the nerve fibre crosses

RACE 2012 Ramachandra Anesthesia Continuing Education

The initial fasciculations seen with succinyl cho-

RACE 2012 Ramachandra Anesthesia Continuing Education

line molecules available and depolarisation can take Channel block

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

polysaccharides synthesized from bacteria. It binds postjunctional occupation by nondepolarisers results

RACE 2012 Ramachandra Anesthesia Continuing Education

Different sites of monitoring and their signifi- Recommended reading

RACE 2012 Ramachandra Anesthesia Continuing Education

01 PHYSIOLOGY OF CEREBRAL PROTECTION

Assistant Professor Satyajeet Misra

RACE 2012 Ramachandra Anesthesia Continuing Education

baseline) and PaO2 > 300 mm Hg results in a 10-30%

Adults ~ 45ml /100g/min

RACE 2012 Ramachandra Anesthesia Continuing Education

Drug Vessel tone CPP CBF CMRO2 Autoregulation CO2

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

Anesthetic neuroprotection CMRO2 and by an anti-apoptotic mechanism, but

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

01 RESPIRATORY PHYSIOLOGY AND ANAESTHESIA

Professor Pankaj Kundra

RACE 2012 Ramachandra Anesthesia Continuing Education

Effect of Anesthesia on Respiratory Physiology is produced by the action on respiratory centre

RACE 2012 Ramachandra Anesthesia Continuing Education

Benzodiazepines decrease chemosensitivity in Ketamine maintains airway patency by promoting

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

Professor Aruna Parameswari

OUTLINE Vapor and gases

Specific vaporizers Vapor pressure

Conclusion When a volatile liquid is kept inside a container

RACE 2012 Ramachandra Anesthesia Continuing Education

Agent Boiling point (°C, 760 mmHg) SVP (torr, 20°C)

Partial pressure It is the number of units of volume of a gas in re-

RACE 2012 Ramachandra Anesthesia Continuing Education

Thermal conductivity - a measure of how fast a • Gas flow rate

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

Conc./Agent Halothane Enflurane Isoflurane Sevoflurane

B) Measured flow vaporizers be done by using baffles or spiral tracks to lengthen

RACE 2012 Ramachandra Anesthesia Continuing Education

the vaporizing chamber. The rod is attached only at

Fig. 3 : Bubble through vaporizer

RACE 2012 Ramachandra Anesthesia Continuing Education

RACE 2012 Ramachandra Anesthesia Continuing Education

• Leaks The ASTM (American Society of Testing and

• Keyed fillers In addition to preventing a vaporizer from being

KEYED FILL SYSTEM SCREW FILL SYSTEM QUIK FIL SYSTEM

Fig 6: Different types of filling systems

RACE 2012 Ramachandra Anesthesia Continuing Education