POSTOPERATIVE &

CRITICAL CARE
MEDICINE

2016 Г.
VITEBSK STATE MEDICAL UNIVERSITY
Content
Postoperative acute pain management.................................................................................................2
Basic pain management guidelines................................................................................................2
Pain assessment and mechanism of pain.......................................................................................2
Analgesic modalities.......................................................................................................................4
Nonpharmacologic measures.........................................................................................................4
Pharmacologic measures................................................................................................................4
IV patient-controlled analgesia.......................................................................................................8
Patient-controlled epidural analgesia...........................................................................................10
Fluid and Electrolyte Balance...............................................................................................................13
Fluid compartments.....................................................................................................................13
Clinical evaluation of fluid status..................................................................................................14
Fluid therapy................................................................................................................................15
Fluid replacement therapy...........................................................................................................18
Blood replacement therapy..................................................................................................................21
Blood products.............................................................................................................................21
Nutrition in Perioperative and Critical Care..........................................................................................24
Basic nutritional needs.................................................................................................................24
How to feed the patient...............................................................................................................26
Complications of nutritional support............................................................................................28
Acid-Base Homeostasis........................................................................................................................31
Normal Acid-Base Physiology.......................................................................................................31
Metabolic Acidosis........................................................................................................................32
Metabolic Alkalosis.......................................................................................................................39
Respiratory acidosis......................................................................................................................43
Respiratory alkalosis.....................................................................................................................46
Sources.................................................................................................................................................48
Postoperative acute pain management
The Joint Commission mandates that all patients have the right to adequate
assessment and management of pain. Better pain control, depending on the agent(s) and
modalities used, leads to benefits not only in terms of cardiovascular and respiratory
complications but also in endocrine, immunologic, gastrointestinal, and hematologic
outcomes. Other reasons to control pain in the postoperative setting are that patients are
often more concerned about being in pain than they are about the primary reason for being
in the hospital, quality of recovery is improved, and acute pain may become persistent if not
treated properly.

Basic pain management guidelines

Listen to and believe the patient: Pain is always subjective, and the provider must
accept the patient’s report of pain. Assess the patient’s level of pain and degree of pain relief
using appropriate tools on a regular basis. A multimodal approach for managing pain is
always better than using a single modality to its limit. This approach may include both
pharmacologic and nonpharmacologic measures and allows for the best possible analgesia
with the lowest incidence of side effects. Always discuss the analgesic plan with the patient
and family, understand the patient’s expectations of pain management, and offer reasonable
goals for the therapy. If pain is present most of the time or expected to last for an extended
period of time (e.g., longer than a few weeks), dose around-the-clock or with long-acting
agents. As-needed (PRN) dosing of immediate-release agents is also needed for
breakthrough pain. If pain is intermittent or expected to last a short time (e.g., less than a
couple of weeks) then PRN dosing of immediate-release agents can be used. Communication
with the patient’s primary care provider regarding the discharge analgesic plan is helpful,
especially if there has been an alteration to a chronic analgesic regimen. Ensure that the
patient has adequate follow-up for the effectiveness of the analgesic regimen and the
development of possible side effects on discharge from the hospital, as well as a plan for a
taper off analgesics; if the patient was not on chronic analgesics before.

Pain assessment and mechanism of pain

It is important to ask the patient about his or her prior analgesic history, what
therapies have either worked or not worked in the past, as well as if he or she was taking
any analgesic agents prior to admission, and, if so, the exact doses. Ask about all the
locations where the patient is experiencing pain and any radiation from the primary
location(s). Have the patient rate the intensity of the pain using scales appropriate to the
patient and situation. The most commonly used measurement tools for intensity of pain in
the postoperative setting are the single-dimension scales. A frequently used variation of this
scale is the verbal numeric scale. Patients are asked to verbally state a number between 0
and 10, where 0 is “no pain at all” and 10 is “the worst pain imaginable,” to correspond to
their present pain intensity. Variations of the single-dimension scales that may be of benefit
in elderly or cognitively impaired populations are scales that use drawn faces ranging from a
content-looking smiling face to a distressed-looking face (e.g., Faces Pain Scale or Wong–
Baker Faces Scale) instead of relying on the patient choosing a number for his or her pain.
The benefits of single-dimension scales are that they are quick and easy to use – this
is important in the acute setting, where repeated measures are needed over a brief period of
time. One disadvantage of single-dimension scales is that they attempt to assign a single
value to a complex, multidimensional experience. Another disadvantage is that patients can
never know if the present experience is the “worst.” A final disadvantage is that these scales
have a ceiling at the uppermost end, so if a value of “10” is chosen and the pain worsens, the
patient officially has no way to express this change. To choose the correct therapy for
treating pain, the underlying mechanism or generator of the pain needs to be determined.
One of the best ways to make this determination is to have the patient use adjectives to
describe the character of the pain (e.g., aching, burning, dull, electric-like, sharp, shooting,
stabbing, tender, throbbing). In the postoperative period it is still important to determine
the impact of the pain on the patient’s functional ability. Specifically, does the pain affect the
patient’s ability to cough, get out of bed, and ambulate while in the hospital?

Figure 1. Mechanisms of pain.

Analgesic modalities
It is important to remember that pain can be helped with nonpharmacologic
measures. In general, the scientific data on the use of these measures are limited; however,
most of the measures have little risk, and, if the patient believes that the therapy is going to
help, then it is likely to be of at least some benefit, due to the cognitive and affective nature
of pain. In terms of pharmacologic measures, many different agents are available in three
basic categories: non-opioid analgesics, opioids, and adjuvant analgesics. There is no one
correct way to treat a patient in pain. It is best to individualize therapy for each patient,
developing a regimen that uses a multimodal approach with the addition or alteration of
agents when pain control is inadequate and an adjustment or diminishing of agents as the
pain resolves.

Nonpharmacologic measures
Application of cold (to reduce inflammation) or heat (to reduce spasms) to muscles or
joints is a commonly employed technique, but the evidence for an actual analgesic benefit is
mixed. Hypnosis has been shown to reduce pain associated with medical procedures;
however, it requires specific training and time to administer. Transcutaneous electrical nerve
stimulation (TENS) has shown conflicting results in terms of an analgesic benefit in the acute
setting, but it has been shown to reduce the need for pharmacologic analgesics. There is
limited evidence of a benefit in the acute setting for relaxation and guided imagery.
Acupuncture and electro-acupuncture have been shown to be of benefit in the acute setting
both to improve pain and to reduce common side effects of opioid analgesics; however, they
require specific training and time to administer.

Pharmacologic measures
Table 2 lists some of the available nonopioid analgesics. Ketorolac is available in the
intravenous (IV) form for patients who are unable to take anything by mouth. Other than
asking the patient if a particular agent has worked or not worked in the past, it is not
possible to determine which opioid may work best for a given patient.
Figure 2. Table Select nonopioid analgesics.

Whenever possible, the enteral route of administration is best as it is the easiest

route and offers the most stable pharmacokinetics. If the enteral route is not available or if
adequate analgesia is not able to be obtained in a timely manner, then IV administration
should be used. Intramuscular administration is not recommended because it is painful and
has variable pharmacokinetics.
With a competent patient, the use of an IV patient-controlled analgesia (PCA) has
been demonstrated to offer the best overall pain management option (see sections on PCA
later). The pronounced individual variability in opioid response, combined with changes in
responsiveness over time, mandates individualization of opioid doses based on a continuing
process of assessment (analgesia and adverse effects) and dose titration.
Table 3 lists the recommended starting doses for moderate to severe pain in the
opioid-naive patient. There are, however, some agents that should not be used, at least first-
line, in the postoperative setting.
Figure 3.Table 3. Recommended starting doses of opioids for adults over

Codeine is not a good first choice because it is possible that approximately 10% to
20% of the population does not have an active form of the enzyme (i.e., cytochrome P450
2D6) necessary to convert codeine into the active drug, morphine.
Morphine is relatively contraindicated in patients with severe renal insufficiency due
to the accumulation of the metabolite morphine-6-glucuronide, which can lead to sedation
and respiratory depression.
Meperidine is not recommended as its active metabolite, normeperidine, can
accumulate in a day or two to levels that cause nervous system excitation (tremors, muscle
twitching, convulsions). In addition, it causes a strong euphoric feeling, especially when given
as an IV push, and it usually causes more nausea than do other agents.
Hydrocodone use needs to be monitored closely because of the acetaminophen
component in the available preparations that can lead to acetaminophen toxicity. Also, non-
medical uses of hydrocodone combination preparations lead to emergency department
visits more frequently than any other pharmaceutical agent.
If a patient is not receiving enough pain relief at a given dose, increase the dose by
25% to 50%. If a patient is having pain before the next dose is due, reduce the interval
and/or increase the dose. Rotation from one opioid to another may be necessary in several
circumstances. The first situation is when a few attempts have been made at increasing the
dose of an opioid and the patient is still not receiving any pain relief, in this case, rotation to
a different opioid may provide better analgesia. A second situation is one in which a patient
is having intolerable side effects; again, rotation to a different opioid may provide a better
side effect profile. A third situation occurs when a particular opioid is not available by the
route of administration required in a given patient. A fourth situation would occur if a
patient has been on an opioid for an extended period of time and is demonstrating signs of
tolerance to the analgesic effects, again, rotation to a different opioid may provide better
analgesia, usually at less than the expected equianalgesic dose due to incomplete cross-
tolerance, which means that the patient will not be “as tolerant” to the new opioid agonist
as he or she was to the one previously taken. Thus, when converting between opioids, for
any of the reasons mentioned above, the calculated equianalgesic dose of the new agent
must be reduced by 25% to 75% to prevent oversedation and/or respiratory depression.
Transdermal fentanyl is not appropriate for acute pain, especially in opioid-naive
patients. There is a black box warning against its use in the acute setting due to the risk of
severe respiratory depression from the delayed peak effect of the drug as the pain level
decreases. It is intended for use in patients who are already tolerant to opioids of
comparable potency.
Methadone is not appropriate as the first-line agent in the acute setting, especially in
opioid-naive patients. Its use requires an understanding of the unique pharmacology of the
drug, especially its extended duration of action and its dose-dependent potency. Also, as it
takes a few days to reach a stable plasma concentration, patients will need to be followed
closely to monitor for effectiveness and side effects. It must also be realized that methadone
is a racemic mixture of a µ-agonist and an N-methyl-d-aspartate (NMDA) antagonist, which
makes patients have a lesser degree of analgesic tolerance development.

Acute pain in the opioid-tolerant patient

In patients with chronic pain on opioids, post-surgical pain adds to the pain burden,
thus opioid use can be expected to be higher than just replacement of what the patient was
on before coming in to the hospital, and can be significantly higher than in opioid-naive
patients. More pain complaints and higher pain scores should be expected. Discussion of
reasonable goals and expectations of analgesic therapy with the patient is crucial. These
patients often know what agents have either worked or not worked for them in the past.
The use of multimodal therapy in this patient population is especially important.
IV patient-controlled analgesia
IV PCA is an excellent therapy for the maintenance of already established analgesia.
Therefore, if a patient is in moderate to severe pain, health care provider-delivered doses of
an opioid must be used to reach an acceptable level of analgesia first because the
incremental dosing of a PCA will not allow patients to achieve comfort in a reasonable period
of time.
PCA may be used in any patient requiring IV opioids provided that he or she is alert,
oriented, and able to understand how to use the equipment appropriately.
PCA parameters. All PCA machines allow for the setting of the following parameters:
demand (bolus) dose, lockout interval, hourly limit, continuous (basal) infusion, and rescue
(loading) dose.
Demand (bolus) dose. The demand dose is the amount of opioid that the patient
receives each time he or she activates the machine. The appropriate choice for the amount
of the demand dose should be small enough so that side effects are minimized yet large
enough to provide effective analgesia.
Lockout interval. The lockout interval is the amount of time following a successfully
delivered demand dose during which the patient can administer no further opioid even if the
system is activated. Lockout intervals between 5 and 10 minutes are commonly used. Even
though the time to peak effect for certain opioids may be longer, there do not appear to be
any data suggesting that any specific time is more or less effective or safe, regardless of the
opioid chosen.
Hourly limit. An hourly limit sets the maximum amount of opioid that can be
administered in the given time period. The proposed purpose for this setting is to add a level
of safety to the system; however, no data support this claim. An hourly limit is automatically
determined by the setting of a demand dose and lockout interval. The use of an hourly limit
less than the predetermined limit based on bolus dose and lockout interval does not make
logical sense, as the patient would be able to get a dose of opioid on schedule for only a part
of every given time period and then not be able to receive anything for the remainder of the
time period.
Continuous (basal) infusion. A continuous infusion delivers a set amount of opioid
every hour without the need for the patient to activate the system. Continuous infusions are
not commonly used, as no documented benefits have been shown for most patients.
Continuous infusions are not recommended in high-risk populations such as elderly patients,
opioid-naive patients, patients concomitantly using other sedatives, and patients with
obstructive sleep apnea or morbid obesity. The use of continuous infusions increases the
overall opioid consumption and has been identified as an independent risk factor for
respiratory depression. Continuous infusions have not been shown to improve patient
satisfaction or pain rating scores, and they do not decrease the frequency of demand dose
use. It may appear to make sense to use a continuous infusion at night when the patient is
sleeping and therefore unable to activate the PCA; however, studies have shown that
nighttime basal infusions do not improve sleep or analgesia. Continuous infusions may be
needed in opioid-tolerant patients, especially those who are chronically taking continuous-
release agents. If the patient cannot take his or her usual doses of opioid enterally, then a
continuous infusion should be used. Determine an IV equivalent for the amount of opioid
that the patient takes in a day (taking into account incomplete crosstolerance if switching to
a different agent), divide this amount by 24 hours, and administer as the hourly continuous
infusion rate.
Rescue (loading) dose. Rescue doses are specific amounts of opioid delivered by a
health care provider that are generally in excess of the patient’s demand dose given when
the level of analgesia from the PCA is inadequate. These doses can also be administered at
the initiation of PCA therapy to initially achieve an adequate level of analgesia at which point
they are more commonly referred to as loading doses. Patients may require a rescue dose
for a variety of reasons while they are on a PCA. There may be brief periods of increased
nociceptive input beyond the ability of the demand dose to be effective (e.g., dressing
changes). If patients forget to or cannot use the PCA for a period of time (e.g., long period of
sleep) they may get behind on their analgesia and require a larger amount of opioid to catch
up.
PCA monitoring. Although there are no actual guidelines for how to monitor patients
on PCA, a recent statement by the Anesthesia Patient Safety Foundation (APSF) offered
recommendations. The APSF advocates the use of continuous monitoring of oxygenation
(i.e., pulse oximetry) and ventilation in patients receiving PCA. The reason for monitoring
both oxygenation and ventilation is that pulse oximetry has reduced sensitivity as a monitor
of hypoventilation when supplemental oxygen is administered. Therefore, when
supplemental oxygen is used, monitoring of ventilation should be undertaken with a
technology designed to assess breathing or estimate arterial carbon dioxide concentrations.
Continuous monitoring is most important for high-risk patients (e.g., patients with
obstructive sleep apnea, morbidly obese patients) but likely should be applied to all patients.

Patient-controlled epidural analgesia

Although this section focuses on the use of patient-controlled epidural analgesia
(PCEA) for the postoperative patient, the concepts can be used in other settings as well (e.g.,
women in labor, cancer patients). APCEA may be used in any patient requiring epidural
analgesia provided that he or she is alert, oriented, and able to understand how to use the
equipment appropriately.
PCEA parameters. All PCEA machines allow for the setting of the same parameters as
described for a PCA.
Demand (bolus) dose. The optimal demand dose for PCEA is not known but is usually
set at 2 to 4 ml. There is no information that a particular demand dose works best with a
certain analgesic regimen.
Lockout interval. Lockout intervals between 10 and 20 minutes are commonly used.
These times are more in line with the peak effect of the analgesics than are the lockout
intervals used for PCA.
Hourly limit. If an hourly limit is used it should be the amount mathematically
determined by the choice of demand dose, lockout interval, and continuous infusion rate.
This determination will ensure that the patient receives analgesics continuously.
Continuous (basal) infusion. Continuous infusions are commonly used for PCEA
management. Continuous infusions are usually started at 4 to 6 ml per hour with the usual
upper limit of 14 ml per hour. Height of the patient does not appear to be a determinant of
the correct infusion rate. There are some data to suggest that weight is positively correlated
and age is negatively correlated with PCEA requirements. It is the location of the surgery,
however, that appears to have the strongest correlation with PCEA requirements in that
thoraco-abdominal operations need higher rates than do lower extremity surgeries. This
increased anesthetic requirement is likely a function of the number of dermatomes that
need to be covered.
PCEA analgesic agents. There does not appear to be a clearly superior regimen for
use in PCEA devices. Local anesthetics are the most commonly used analgesic agents.
Classically, bupivacaine is the most commonly used local anesthetic due to its relative
resistance to tachyphylaxis. The cardiotoxicity of bupivacaine has led some practitioners to
the use of levobupivacaine or ropivacaine instead.

The next most common agents used for PCEA therapy are the opioids. They are
commonly used in combination with a local anesthetic. There seems to be no benefit of
administering lipophilic opioids (i.e., fentanyl or sufentanil) solely via the epidural route. The
site of action of lipophilic opioids when given epidurally is not clear. Studies looking at the
efficacy of fentanyl and sufentanil given epidurally versus IV are contradictory. Most studies
measuring the plasma concentrations of these opioids when given via an epidural or IV have
shown no difference in levels, thus suggesting that the major site of action is not at the
spinal cord but rather due to systemic absorption. Hydrophilic opioids (i.e., morphine or
hydromorphone), in contrast, maintain high cerebrospinal fluid levels for an extended period
of time and therefore can act at the opioid receptors in the spinal cord.
Other agents have been studied as adjuvant medications added in combination with
local anesthetics and/or opioids for epidural use; however, they are not used extensively in
most clinical practices. This is likely because the studies are limited and show equivocal
results. The major proposed benefits are improved analgesia and an analgesic sparing effect
(i.e., the ability to use lower concentration of the other agents, specifically local anesthetics
and opioids). A major concern with the addition of clonidine has been an increased incidence
of hypotension and sedation. Use of epinephrine has shown improved analgesia with
activity, although it may lead to an increased incidence of motor block. Epinephrine use also
has been shown to reduce plasma concentrations of lipophilic opioids by allowing them to
remain in the neuraxis for long enough to actually bind to the opioid receptors in the spinal
cord. The concern with neostigmine is that, when used for intrathecal administration, a
dose-dependent incidence of nausea and vomiting occurs as well as sedation but epidural
use does not seem to have the same increased incidence of nausea and vomiting, and only
minimal sedation occurs, if at all. Also, when neostigmine is started preoperatively it may
provide some degree of a preemptive analgesic effect.
PCEA complications/side effects. Epidural infusions are associated with complications
related to the placement of epidural catheters and medications used. The incidence of
serious, permanent neurologic complications is exceedingly rare, and data comprise mostly a
handful of case reports. The incidence of spinal hematoma has classically been thought to be
1:150,000 in the presence of normal coagulation, although recent studies have suggested
that it may be more common. The incidence of epidural hematoma formation in a patient
who is anticoagulated is not known, but it is estimated at 1:3000 in patients receiving
therapeutic low-molecular-weight heparin. Epidural abscess incidence is not known but is
considered rare (at most 0.05%). Risk factors for abscess formation may be longer times of
having the epidural in place (possibly >6 days) as well as use in immunocompromised
patients. Intrathecal or intravascular migration of an epidural catheter is estimated at
approximately 0.2%, although it is likely much less frequent. The incidence of premature
catheter dislodgement is estimated at approximately 6%. The major side effects due to local
anesthetics in epidurals are hypotension, central nervous system (CNS) toxicity, and motor
block. The probability of hypotension from an epidural does not rise above 1% to 2% until
the spread of the epidural is beyond 14 sympathetic dermatomes. In most instances, the
band of analgesia, plus another 6 dermatomes for the spread of the sympathetic blockade
beyond the analgesic level, is less than 14 dermatomes. The major mechanism by which an
epidural might cause hypotension is through decreased venous return (preload) from
reduced venous capacitance; therefore, the most appropriate treatment is increasing cardiac
preload by increasing intravascular volume. Hence, hypotension is rarely seen in the supine
normovolemic patient. Thus it is often the fluid status of the patient that is more of a
causative factor than the epidural itself. This is evidenced by the fact that stopping the
epidural infusion in a patient often does not improve blood pressure unless the pain
becomes so great that a large sympathetic response occurs.
CNS toxicity (seizures) from systemic accumulation of local anesthetics is obviously
based on the total amount of the drug used over time and has an estimated incidence of
0.01% to 0.1%. Motor block of the lower extremities is estimated at less than 3% when lower
concentrations of local anesthetic are used and greater than approximately 25% with higher
concentrations. The incidence of nausea and/or vomiting with opioid containing PCEA
therapy is estimated at between 4% and 15%, although higher incidences have also been
reported. The incidence of severe pruritus is between 2% and 17%, with the incidence of any
degree of pruritus likely being well over 50%. Sedation is reported to occur in approximately
15% of patients. Respiratory depression is estimated to occur in 0.1% to 0.4% of patients. A
higher incidence (approaching 1.5%) of respiratory depression is seen in some studies using
morphine.
Fluid and Electrolyte Balance
Despite the fact that fluid replacement therapy is one of the most fundamental
elements of the anesthetic and critical care of patients, it remains one of the most difficult.
Because of a lack of clear data there are no precise rules for the amount, timing, or type
(crystalloid vs. colloid or which type of either) of fluid replacement, nor for the hematocrit
target for RBC replacement. To further complicate the issue it is not clear on which
monitoring parameter the volume given should be based, especially if invasive monitoring is
not used.

Fluid compartments
Understanding the general composition of the fluid compartment is the first step in
the optimal management of fluids, electrolytes, and acid–base status in the operative and
critically ill patient. The multiple fluid compartments are separated by semipermeable
membranes through which water can move freely. The total body water (TBW) ranges from
50% (females) to 60% (males) of body mass, is distributed differentially among body tissues,
and is divided into the following compartments:
 Intracellular water is approximately 66% of the TBW (40% of the body mass)
 Extracellular water is approximately 34% of the TBW (20% of the body mass) and can be
further divided:
 Intravascular water is made up of plasma and is approximately 8% of TBW (5%
of the body mass).
 Extravascular water is composed of lymph, interstitial fluid, bone fluid, fluids
of the various body cavities, and mucosal secretory fluids, and represents
approximately 25% of TBW (15% of the body mass).
Movement of water is determined by osmotic and hydrostatic pressure differences.
The movement of water directly from tissue into the vasculature and the control of the flux
by the relative hydrostatic and osmotic pressures in the two compartments was originally
hypothesized by Ernest Starling in 1896.
Oncotic pressure (osmotic pressure in the intravascular compartment) is the result of
negatively charged intravascular proteins to which vascular membranes are impermeable or
positive ions that are associated with the negatively charged proteins. Albumin is the protein
mainly responsible for the oncotic pressure (two-thirds of the total).
Clinical evaluation of fluid status
One goal of the evaluation is to determine the presence of hypovolemia or
hypervolemia before the surgical procedure begins. Patients presenting in septic shock,
those who may have undergone a bowel preparation preoperatively, or those who are
otherwise physiologically deranged may be hypovolemic. Both hypovolemia and
hypervolemia are associated with significant risks. Signs of hypo- and hypervolemia are
summarized in tables below.
Signs Fluid loss (percentage of body weight)
5% 10% 15%
Mucous membrane Dry Very dry Parched
Sensorium Norma Lethargic Obtunded
Orthostatic changes None Present Marked
Heart rate >15 bpm↑
Blood pressure >10 mm Hg↓
Urinary flow rate Mildly decreased Decreased Markedly decreased
Pulse rate Normal or increased Increased>100 Markedly
bpm increased>120 bpm
Blood pressure Normal Mildly decreased Decreased
with respiratory
variation
Figure 4. Signs and symptoms of hypovolemia

Early signs Late signs

 Pitting edema – presacral in the  Tachycardia
bedridden patient or pretibial in the  Pulmonary crackles, wheezing,
ambulatory patient cyanosis, and pink, frothy
 Increased urinary flow pulmonary secretions

Figure 5. Signs and symptoms of hypervolemia

In addition, certain laboratory values, while very nonspecific, may help in assessment
of volume status. For example, a high hematocrit, or plasma [Na +] may indicate a total body
water deficit. A high blood urea nitrogen, a base deficit, a low mixed venous PO2, or urine
output may indicate an inadequate cardiac output. A low central venous or pulmonary
artery pressure, and a high pulse rate suggest inadequate intravascular volume.
In addition, indirect signs, such as the response of blood pressure to changes in
patient positioning or positive pressure ventilation, the change in stroke volume to positive
pressure ventilation or the vasodilating or negative inotropic effects of anesthetics, may aid
in the assessment of volume status. Although it is true that all the above signs may be
helpful in the aggregate and when combined with other findings, it must be remembered
that they are nonspecific and are altered by drugs used in the perioperative period and the
physiologic effects of surgical stress.

Fluid therapy
Perioperative fluid therapy includes the replacement of:
 Preexisting fluid deficits.
 Normal losses (maintenance requirements).
 Surgical wound losses (including blood losses).
Evaluation of preexisting fluid deficit.
The constitutive daily losses of water and electrolytes are usually replaced by a
maintenance fluid intake, calculated according to the data listed in tables below. Calculation
of estimated hourly fluid needs is shown in Fig.7.

Daily water loss

Insensible water losses:
Normal losses by skin and lungs: 600–800 ml/d
Sensible water losses:
From kidney and gastrointestinal tract: 1700 ml/d
Figure 6. Daily water loss

Hourly maintenance fluid replacement (based on body weight)

Body weight Fluid
0–10 kg 4 ml/kg/h
For the next 11–20 kg Add 2 ml/kg/h
For each kg above 20 kg Add 1 ml/kg/h for each kg above 20 kg
Figure 7. Hourly maintenance fluid replacement

Preoperative fluid deficits should also take into account fluid deficits due to the
conditions listed in Fig.8. Electrolytes are usually replaced by administration of salt solutions.
Although intraoperative glucose replacement is not routinely recommended, the protein-
sparing effect of parenteral glucose is one of the goals of basic glucose intravenous therapy
in critically ill patients. Administration of at least 100 g/d of glucose reduces protein loss by
more than one half. As a caloric source supplement, glucose intake should range from 100 to
200 mg/kg/h.

Fluid losses in various clinical situations

Abnormal fluid losses:
 Preoperative bleeding
  Vomiting
 Diuresis
Occult losses:
 Traumatized tissues
 Infected tissues
 Ascites
Increased insensible losses due to:
 Hyperventilation
 Fever
 Sweating
Figure 8. Fluid losses in various clinical situations

Maintenance requirements.
Patients often present for surgery after an overnight fast without any fluid intake.
This does not reduce blood volume. The presumed fluid deficit is proportional to the
duration of the fast. This deficit can be estimated by multiplying the normal maintenance
rate as shown in Table 7 by the length of the fasting period.
For example, for the average 70-kg person fasting for 8 hours, this amounts to
(40+20+50) ml/h×8 hours, or 880 ml. (In reality, this deficit will be significantly less as a
result of normal renal conservation, though replacement of this amount is routine in
practice.) Ideally, all deficits should be replaced preoperatively in all patients. The fluids used
should be similar in composition to the fluids lost. With fever, each degree above 98.6◦ F
(37◦ C) requires one to add 2.5 ml/kg/d for an increase in insensible losses. It should be
realized, however, that crystalloids are physiologically distributed over the entire
extracellular space. This implies that up to 80% of the fluid administered will leave the
intravascular compartment (over a time course on the order of 30minutes). However, the
final distribution of the fluids will depend somewhat on the state of intravascular volume
when it was given.

Surgical fluid losses.

Evaporative and redistributive losses Intraoperative fluid losses are mainly the result
of evaporation and internal redistribution of body fluids. Evaporative losses classically have
been assumed to be directly proportional to the surface area of the exposed surgical wound
and the duration of the surgical procedure, leading to gross overestimation of intraoperative
fluid requirements and overhydration. Experiments using humidity chambers indicate that
evaporative losses in adults undergoing extensive abdominal procedures merely increase to
about 1 ml/kg/h. Redistribution appears to be related to the extent of surgical trauma.
Internal redistribution of fluids is often called “third spacing” because large amounts of fluid
are sequestered into the interstitial space or translocated into anatomic spaces, such as the
bowel lumen. This occurs with burns, extensive injuries, surgical dissections, or peritonitis
but is also directly proportional to the amount of fluids infused. Lastly, significant losses of
lymphatic fluid may occur during extensive retroperitoneal dissections.

Classical procedural classification of redistribution and evaporative surgical fluid

Scale of surgery Additional fluid reguirement
Minimal (herniorrhaphy) 1–2 ml/kg
Moderate (appendectomy) 2–4 ml/kg
Severe (colectomy) 4–8 ml/kg
Figure 9. Classical procedural classification

Blood loss.
Monitoring and estimating blood loss (table below) is important for guiding fluid
therapy and blood product transfusions. Selection of the type of intravenous solution
depends on the surgical procedure and the expected blood loss:
 Minimal blood loss and fluid shifts: maintenance solutions
 All other procedures: lactated Ringer’s solution
Methods for estimating blood losses
Empiric measurements Laboratory
Measurement of blood in the surgical suction Serial hematocrit or hemoglobin may be useful
container (adjusted to account for the volume during long procedures or when estimates are
of irrigating solutions) difficult (their concentrations reflect the ratio of
Visual estimation of the blood on surgical
blood cells to plasma, not necessarily blood
sponges and laparotomy pads (“laps”):
loss; rapid fluid shifts and intravenous
Fully soaked sponge (4×4) holds 10 ml of blood
replacement affect measurements)
Soaked “lap” holds 100–150 ml of blood (the
size of laparotomy pads may vary considerable
among institutions)
More accurate estimates are possible if sponges
and laparotomy pads are weighed before and
after use. This is especially important when
large numbers are used or, for example, in
pediatric patients.
Figure 10. Methods for estimating blood losses.
Fluid replacement therapy.
Fluid replacement therapy should optimize cardiac preload and ensure adequate
tissue oxygenation. It may consist of infusions of crystalloids, colloids, or a combination of
both. The correct choice of fluid replacement therapy depends on the source and type of
fluid that has been lost. In practice it is not known where the losses come from or their
composition. Therefore, typically half-normal solutions are sometimes preferred for
replacement of insensible losses and isotonic fluids (normal saline, lactated Ringer’s or
colloids) are preferred for all other deficits.
Crystalloid solutions.
Crystalloid solutions are electrolyte solutions of low molecular weight ions (salts)
dissolved in water, with or without glucose. These solutions may be isotonic, hypotonic, or
hypertonic. Crystalloid solutions are very inexpensive. They rapidly equilibrate with and
distribute in the extracellular fluid space, expanding the interstitial space more than the
intravascular volume. Crystalloids are used for maintenance and usually for the initial
resuscitation fluid in the operative setting. Because administration of large amounts of saline
often leads to a metabolic acidosis due to hyperchloremia, lactated Ringer’s is the most
common choice. In selecting between lactated Ringer’s and saline, the patient’s sodium-to-
chloride ratio and the acid–base balance should be considered. Lactated Ringer’s solution
contains potassium and should be used with caution in patients with hyperkalemia or renal
failure. Because they contain calcium, Ringer’s solutions should not be used to dilute citrated
blood products.
Colloid solutions.
Colloid solutions contain high molecular weight substances, such as proteins and
large glucose polymers dissolved in a solute. Most colloid solutions are dissolved in isotonic
saline but are available also as isotonic glucose and nonglucose solutions, as well as
hypertonic saline solutions. For the most part, in healthy patients they remain intravascular
and help maintain the oncotic pressure. Although the intravascular half-life of a crystalloid
solution is 30 minute to 1.5 hours, most colloid solutions have intravascular half-lives of 4 to
6 hours.
Types of colloids
Dextrose starches (dextran) – improves blood flow in the microcirculation by decreasing blood
viscosity.
Dextran 70 (Macrodex; Pharmacia, Piscataway, NJ) – average molecular weight of 70,000. Dextran
40 (Rheomacrodex; Pharmacia) – average molecular weight of 40,000
 Dose: shock – 10 ml/kg infused rapidly; 20 ml/kg maximum 1st 24 h;
10 ml/kg maximum beyond 24 h
First-generation HES: Hetastarch – 6% solution with an average molecular weight of 450,000 Da,
molar substitution 0.7, C2/C6ratio 6:1
Dose: volume expansion – 500–1000 ml (1500 ml/d maximum, 20 ml/kg/h rate)
Second-generation HES: pentastarch – 6% solution with average molecular weight of 264,000 Da,
molar substitution 0.45, C2/C6ratio 5:1
Dose: volume expansion: 500–2000 ml (2000 ml/d maximum, 20 ml/kg/h rate)
HES 130/0.4 (Voluven; Fresenius Kabi, Bad Hmburg, Germany): 6% solution
with mean molecular weight 130,000 Da, molar substitution 0.4, C2/C6ratio 9:1
Dose: volume expansion: 500–2000 ml (3500 ml/d maximum, 20 ml/kg/h rate)
HES, hydroxyethyl starch.
Figure 11. Types of colloids

Colloid solutions should be used cautiously in patients with bleeding disorders,

congestive heart failure, or renal disease with oliguria or anuria. The primary difference
between Hetastarch and Pentastarch is that the latter has less variability in molecular size in
addition to having a smaller average molecular size. The larger molecules contained in
Hetastarch, of several million daltons and higher, are taken up by phagocytes in the
reticuloendothelial system and are never metabolized or excreted. That is why the limit of
units of Hetastarch is a lifetime limit. A reasonable molecular analogy is asbestos. Despite
theoretical advantages and some demonstrated physiologic benefits in a few small studies,
several large, multicenter randomizedand observational cohort trials have failed to
demonstrate any outcome advantage from colloid solutions over crystalloids.

Adverse effects associated with colloids

Colloid Adverse effects
Dextran Antiplatelet effect (decreased aggregation), prolonged bleeding time,
interference with blood typing, allergic reactions, renal failure
Hetastarch High doses (>1 L) may cause coagulation abnormalities (reduction in
factor VIII and vWF, prolonged PTT). Newer formulations – i.e. third-
generation HES 130/0.4 (Voluven; Fresenius Kabi, Bad Homburg,
Germany) show improved safety profiles due to lower molecular size.
Albumin Expensive; relatively short intravenous half-life
HES, hydroxyethyl starch; PTT, partial thromboplastin time; vWF, von Willebrand factor
Figure 12. Adverse effects associated with colloids

Several types of colloid solutions are available for clinical use, including:
 Blood-derived colloids: albumin (5% and 25% solutions) and plasma protein fraction
(5%). (Plasma protein fraction contains α –and β -globulins in addition to albumin and
may lead to allergic, hypotensive reactions.)
 Synthetic colloids: dextrose starches and gelatins (table 11). Gelatins are associated with
histamine-mediated allergic reactions and are not available in the United States.
Although isotonic saline and colloid-containing solutions both have been used to
replace extracellular fluid deficits, controversy exists regarding the use of colloid versus
crystalloid fluids for fluid resuscitation. There are two possible theoretical advantages of a
colloid-containing solution over fluid repletion with saline:
 More rapid plasma volume expansion, because the colloid solution remains in the
vascular space (replacing an intravascular volume deficit with crystalloids generally
requires three to four times the volume needed when compared with colloids)
 Less risk of pulmonary edema, because dilutional hypoalbuminemia will not occur.
However, as noted earlier, randomized controlled trials and systematic meta-
analyses have failed to demonstrate any advantage in terms of pulmonary complications or
survival for using colloid-containing solutions. Crystalloid (usually lactated Ringer’s if large
volumes are given quickly) solutions are therefore generally preferred. The solutions seem to
be at least as safe and effective as colloid-containing solutions while costing much less. At
the same time, it is important to keep in mind that rapid administration of large amounts of
crystalloids (>4–5L) is associated with significant tissue edema. Marked tissue edema may
impair oxygen transport, tissue healing, and return of bowel function following major
surgery.

Blood replacement therapy

Blood products
Blood component administration carries a significant risk of infectious, toxic, and
immunologic complications. All clinicians must be familiar with indications and alternatives
to decrease the risks of this therapy.

Red blood cells

Red blood cells (RBCs) are given to improve oxygen (O2)-carrying capacity and do not
contain viable platelets or significant amounts of coagulation factors or neutrophils. All RBC
transfusions must be ABO compatible. RBC units are stored at 1◦ to 6◦C to decrease
metabolism and inhibit bacterial growth. A unit of RBCs (often referred to as “packed” red
cells) is prepared from whole blood using a closed sterile system. First, approximately 450 ml
of whole blood is collected from a screened volunteer donor into a bag containing 63 ml of a
citrate-phosphate-dextrose (CPD) anticoagulant preservative. The donated whole blood unit
may then be processed to produce one RBC unit, one platelet concentrate, and one unit of
fresh frozen plasma (FFP). To generate a unit of RBCs, a whole blood unit is centrifuged to
separate the RBCs from the plasma. Most of the plasma is then expressed from the unit,
leaving about 180 (160–275) ml of RBCs, 30 ml of residual plasma, and 30 ml of CPD solution.
Such a CPD RBC unit has a volume of about 250 ml and a hematocrit (Hct) of 70% to 80%,
and may be stored for up to 21 days.

Leucocyte-reduced red blood cells

Patients who have a history of febrile nonhemolytic transfusion reactions, require
cytomegalovirus-negative blood, are at risk for HLA alloimmunization, or are receiving an
exchange transfusion should receive leukocyte-depleted RBCs. These RBC units are prepared
with special filters that remove ≥ 99.99% of white blood cells (WBCs) prior to storage.
Leukoreduction is usually effective in preventing febrile nonhemolytic transfusion reactions
and also has been shown to be effective in decreasing platelet alloimmunization and
cytomegalovirus transmission. The filtration system used will remove some portion of the
other cellular components present but the RBC unit should still have a therapeutic efficacy
equal to at least 85% of the original component. Leukoreduction does not prevent graft-
versus host disease (GVHD).

Washed red blood cells

Patients who have a history of severe reaction to transfusion, such as anaphylactoid
reactions, should receive washed RBCs. RBCs are washed using 0.9% sodium chloride to
remove almost all IgA (99%) and other plasma proteins and WBCs. This may not be sufficient
to prevent hypersensitivity reactions, so blood collected from an IgA-deficient donor may be
needed to support an IgA-immunized patient. Because units are typically washed using an
open system, washed products must be transfused within 4 hours of preparation. The wash
process reduces RBC content by approximately 20%.

Platelets
Platelet transfusions are indicated to prevent or treat bleeding in patients with
qualitative or quantitative platelet deficiencies. Platelet concentrates (“random donor
platelets”) are derived from donated whole blood. First, a whole blood unit is gently
centrifuged (“soft spin”) to produce a bag of platelet-rich plasma (PRP) plus one unit of RBCs
(see earlier). The PRP is centrifuged a second time (“hard spin”) to produce a platelet
concentrate plus one unit of plasma. The platelet concentrate is resuspended in 40 to 70 ml
of plasma and should contain a minimum of 5.5×10 11 platelets. Platelet concentrates are
stored at room temperature (20◦–24◦C) with continuous gentle agitation for up to 5 days.
Platelet metabolic activity continues during storage; agitation of platelet units facilitates gas
exchange and helps preserve the pH of the unit. Because platelets are stored at room
temperature, bacterial growth may occur during storage. Rarely, septic transfusion reactions
are observed, particularly in immunocompromised recipients. Platelet concentrates are
usually pooled into packs of four to six units of platelets for transfusion in adults. Pooling
requires entry into the sterile units, so platelet concentrates are required to be transfused
within 4 hours of pooling. Low numbers of RBCs are present in platelet concentrates. Rarely,
Rh sensitization may be induced if an Rh-positive platelet unit is transfused to an Rh-
negative recipient, but sensitization can be prevented by administering Rh immune globulin.

Fresh frozen plasma

FFP is prepared by centrifuging a unit of whole blood. One unit of FFP has a volume of
approximately 225 ml (200–250 ml) and contains all clotting factors in normal concentrations
(1 IU/ml), as well as fibrinogen. FFP is frozen within 8 hours of collection to avoid
degradation of coagulation factors (particularly the labile factors V and VIII). ABO-compatible
FFP is generally used, but transfusing ABO-compatible FFP is not required. FFP is the primary
source of replacement coagulation factors for patients with multiple factor deficiencies, and
is the component most prone to inappropriate use. Indications for the use of FFP include
correction of bleeding due to factor deficiencies (when specific factor concentrates are not
available) and states in which multiple factor deficiencies must be corrected (e.g., massive
hemorrhage and transfusion, DIC, hepatic failure, acute reversal of warfarin therapy). These
deficiencies should be demonstrated by abnormal coagulation studies (prothrombin time
[PT] or activated partial thromboplastin time. Minor prolongations of the PT and aPTT (<1.5
× the mean of normal range), volume expansion, and nutritional support are not indications
for FFP transfusion. Reversal of warfarin should be treated with vitamin K rather than FFP,
unless more urgent correction is required (e.g., for ongoing hemorrhage). There are
advantages and disadvantages to using Vitamin K versus FFP. The latter has the associated
transfusion risks, but its action is essentially instantaneous and it permits the easy
reestablishment of anticoagulation with warfarin. With Vitamin K, there is no transfusion
risk; however, its action requires hours to be manifest. In addition, a patient given Vitamin K
becomes temporarily very resistant to warfarin, and this resistance decreases gradually over
a period of weeks. Therefore, it becomes very difficult to establish a constant anticoagulant
effect with warfarin for weeks following a dose of Vitamin K. One milliliter of FFP per
kilogram of patient weight will raise most clotting factors by approximately 1%, so one unit
of FFP will raise factor levels in a 70-kg adult by about 3%. In clinically significant
coagulopathy, one to two units of FFP likely is inadequate. The amount of FFP needed
depends on the patient’s clotting factor levels, levels needed to achieve a therapeutic effect,
whether or not the patient is bleeding, and the patient’s blood volume.

Cryoprecipitate
Cryoprecipitate is a concentrate prepared by thawing FFP at 1◦to 6◦C and isolating
and refreezing the cold-insoluble precipitate that forms. Each unit of cryoprecipitate
contains about 80 units each of factor VIII and von Willebrand factor and about 200 mg of
fibrinogen, as well as lesser quantities of fibronectin and factor XIII. When needed, the unit is
thawed, suspended in normal saline, and often pooled for administration. It must be used
within 6 hours of thawing or, if pooled, within 4 hours. Compatibility testing is not needed,
nor is ABO or Rh type specificity, although in infants, specificity is often observed if trace
amounts of A or B isoagglutinins are present (because of their small blood volume).
Historically, cryoprecipitate was used for hemophilia and von Willebrand’s disease, although
now virus-inactivated factor concentrates are preferred. It is primarily used for control of
bleeding with hypofibrinogenemia, such as acute DIC with bleeding. Each unit should raise
the fibrinogen level in an adult by 0.1 mg/kg/dl.
Nutrition in Perioperative and Critical Care
Basic nutritional needs
Maintenance of normal body mass, composition, structure, and function requires the
periodic intake of water, energy substrates, and specific nutrients. Nutrients that cannot be
synthesized from other nutrients are characterized as “essential.” Remarkably, relatively few
essential nutrients are required to form the thousands of compounds that make up the
body. Known essential nutrients include 8–10 amino acids, 2 fatty acids, 13 vitamins, and
approximately 16 minerals.
Energy is normally derived from dietary or endogenous carbohydrates, fats, and
protein. Metabolic breakdown of these substrates yields the adenosine triphosphate
required for normal cellular function. Dietary fats and carbohydrates normally supply most
of the body’s energy requirements. Dietary proteins provide amino acids for protein
synthesis; however, when their supply exceeds requirements, amino acids also function as
energy substrates.
The metabolic pathways of carbohydrate, fat, and amino acid substrates overlap;
such that some interconversions can occur through metabolic intermediates (see Figure 13).
Excess amino acids can therefore be converted to carbohydrate or fatty acid precursors.
Excess carbohydrates are stored as glycogen in the liver and skeletal muscle. When glycogen
stores are saturated (200–400 g in adults), excess carbohydrate is converted to fatty acids
and stored as triglycerides, primarily in fat cells. During starvation, the protein content of
essential tissues is spared. As blood glucose concentration begins to fall during fasting,
insulin secretion decreases, and counter regulatory hormones, such as glucagon, increase.
Hepatic and, to a lesser extent, renal glycogenolysis and gluconeogenesis are enhanced. As
glycogen supplies are depleted (within 24 h), gluconeogenesis (from amino acids) becomes
increasingly important. Only neural tissue, renal medullary cells, and erythrocytes continue
to utilize glucose—in effect, sparing tissue proteins. Lipolysis is enhanced, and fats become
the principal energy source. Glycerol from the triglycerides enters the glycolytic pathway,
and fatty acids are broken down to acetyl-coenzyme A (acetyl-CoA). Excess acetyl-CoA
results in the formation of ketone bodies (ketosis). Some fatty acids can contribute to
gluconeogenesis. If starvation is prolonged, the brain, kidneys, and muscle also begin to
utilize ketone bodies efficiently.
Figure 13. Important metabolic pathways in hepatocytes.

The previously well-nourished patient undergoing elective surgery could be fasted for
up to a week postoperatively without apparent adverse effect on outcomes, provided fluid
and electrolyte needs are met. The usefulness of nutritional repletion in the immediate
postoperative period is not well defined, but likely relates to the degree of malnutrition,
number of nutrient deficiencies, and severity of the illness/injury.
Moreover, the optimal timing and amount of nutrition support following acute illness
remain unknown. On the other hand, malnourished patients may benefit from nutritional
repletion prior to surgery. Modern surgical practice has evolved to an expectation of an
accelerated recovery. Accelerated recovery programs generally include early enteral feeding,
even in patients undergoing surgery on the gastrointestinal tract, so prolonged periods of
postoperative starvation are no longer common practice. All well-nourished patients should
receive nutritional support after 5 days of postsurgical starvation, and those with ongoing
critical illness or severe malnutrition should be given nutritional support immediately. The
malnourished patient presents a different set of issues, and such patients may benefit from
both preoperative and early postoperative feeding. Clearly, the healing of wounds requires
energy, protein, lipids, electrolytes, trace elements, and vitamins. Depletion of any of these
substrates may delay wound healing and predispose to complications, such as infection.
Nutrient depletion may also delay optimal muscle functioning, which is important for
supporting increased respiratory demands and early mobilization of the patient.
The resting metabolic rate can be measured (but often inaccurately) using indirect
calorimetry (known as a metabolic cart) or by estimating energy expenditure using standard
nomograms (such as the Harris–Benedict equation), yielding an approximation of daily
energy requirements. Alternatively, a simple and practical approach assumes that patients
require 25–30 kcal/kg daily. The weight is usually taken as the ideal body weight or adjusted
body weight. Even though nutritional requirements can increase greatly above basal levels
with certain conditions (eg, burns), the more often relevant reason for determining the daily
requirements is to ensure that patients are not unnecessarily overfed. In this regard, obese
patients require adjusting the body weight based on the degree of obesity to prevent
overfeeding.

How to feed the patient

Enteral nutrition generally refers to any method of feeding that uses the
gastrointestinal (GI) tract to deliver part or all of a person's caloric requirements. It can
include a normal oral diet, the use of liquid supplements or delivery of part or all of the daily
requirements by use of a tube (tube feeding).
Parenteral nutrition (PN) is feeding a person intravenously, bypassing the usual
process of eating and digestion. The person receives nutritional formulae that contain
nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals. It is
called total parenteral nutrition (TPN) or total nutrient admixture (TNA) when no significant
nutrition is obtained by other routes. It may be called peripheral parenteral nutrition (PPN)
when administered through vein access in a limb, rather than through a central vein.
After total parenteral nutrition (TPN) was established as a feasible approach for
feeding patients lacking a functional gut, physicians extended the practice of TPN to many
circumstances where “logic” and “clinical experience” suggested that it would be better than
EN. For example, one such indication was in the patient with acute pancreatitis, where, in
the 1970s, many clinicians thought that a period of TPN would put the gut and pancreas at
“rest,” allowing for resolution of pain and weight loss. Unfortunately, “logic” and “clinical
experience” were incorrect.
Now, the worldwide consensus expressed in clinical practice guidelines is that
patients with acute pancreatitis (and indeed all others with functioning guts) will have worse
outcomes if TPN is provided, rather than EN. Today, the indications for TPN are narrow and
include patients who cannot absorb enteral solutions (small bowel obstruction, short gut
syndrome, etc.); partial PN may be indicated to supplement EN, in cases in which EN cannot
fully provide for nutritional needs. In the latter circumstance, recent evidence suggests that
the decision to add supplemental PN should be made only after a week’s time in previously
well-nourished patients. In short, EN should be the primary mode of nutritional support,
and PN should be used when EN is not indicated, not tolerated, or insufficient. There was a
time when nearly every physician who took care of critically ill patients was in the position of
frequently ordering TPN for patients. This is no longer the case, given that EN is now so
much more widely employed. As a consequence, many hospitals and health systems insist
that a nutrition support team take responsibility for those rarer patients who require TPN.
In general, patients with critical illness should undergo whatever initial
hemodynamic resuscitation they require before initiation of nutritional support (either EN or
PN). Absorption, distribution, and metabolism of nutrients require tissue blood flow, oxygen,
and carbon dioxide removal. Adequate tissue blood flow requires an adequately resuscitated
patient. Nutrient delivery to ischemic tissues may cause tissue damage by increasing carbon
dioxide and oxidant production while consuming energy. Patients with critical illness who
require EN will usually require placement of a feeding tube. Feeding tubes may be placed in
to the stomach in patients with adequate gastric emptying and low risk of aspiration. In
patients with delayed gastric emptying or those at high risk of aspiration, feeding tubes are
best placed in to the small intestine. Ideally, the tip of such tubes will be sited within the
small intestine, either by transpyloric placement of a nasoenteraltube or directly in to the
jejunum during abdominal surgery (via a percutaneous route), reducing the likelihood of
gastric distention and regurgitation. Patients, who are unable to eat, but require EN over
long periods, will often undergo percutaneous endoscopic placement of gastrostomy (PEG)
tubes (the tips of such tubes can be placed distal to the pylorus). One should confirm that
the tips of all feeding tubes are appropriately placed before initiating feeds to reduce the
likelihood that EN solutions will be accidentally infused, say, in to the tracheobronchial tree
or abdominal cavity.
TPN will generally require that a venous access line be placed with the catheter tip in
the superior vena cava. Peripheral PN can support the nutritional requirements of the
patient, but necessitates the use of larger volumes of fluids due to the requirement for lower
osmolarities than used with central PN and increases the risk of phlebitis. The line or port
through which the TPN solution will be infused should be dedicated to this purpose, if
possible, and strict aseptic techniques should be employed for insertion and care of the
catheter.

Complications of nutritional support

Diarrhea is a common problem with enteral feedings and may be related to either
hyperosmolarity of the solution or lactose intolerance. Gastric distention is another
complication that increases the risk of regurgitation and pulmonary aspiration; the use of
duodenal or jejunostomy tubes should decrease the likelihood of gastric distention.
Complications of TPN are either metabolic or related to central venous access.
Bloodstream infections associated with central and peripheral venous lines remain a major
concern, particularly in the patient with critical illness and immunocompromised states.
Overfeeding with excess amounts of glucose can increase energy requirements and
production of carbon dioxide; the respiratory quotient can be >1 because of lipogenesis.
Overfeeding can lead to reversible cholestatic jaundice. Mild elevations of serum
transaminases and alkaline phosphatase may reflect fatty infiltration of the liver as a result
of overfeeding.

Complications of total parenteral nutrition.

Catheter-related complications
Pneumothorax
Hemothorax
Chylothorax
Hydrothorax
Air embolism
Cardiac tamponade
Thrombosis of central vein
Bloodstream infection
Metabolic complications
Azotemia
Hepatic dysfunction
Cholestasis
 Hyperglycemia
- Hyperosmolar coma
- Diabetic ketoacidosis
Excessive CO2 production
Hypoglycemia (due to interruption of infusion)
Metabolic acidosis or alkalosis
Hypernatremia/Hyperkalemia
Hypokalemia/Hypocalcemia/Hypophosphatemia
Hyperlipidemia
Pancreatitis
Fat embolism syndrome
Anemia
Vitamin D, K, or B-12 deficiency
Essential fatty acid deficiency
Hypervitaminosis A
Figure 14. Complications of total parenteral nutrition.

ESPEN Guidelines on Parenteral Nutrition: Intensive care 2009. Summary.

Subject Recommendations
Indications Patients should be fed because starvation or underfeeding in ICU patients is
associated with increased morbidity and mortality. All patients who are not
expected to be on normal nutrition within 3 days should receive PN within 24
to 48 h if EN is contraindicated or if they cannot tolerate EN.
Requirements ICU patients receiving PN should receive a complete formulation to cover their
needs fully. During acute illness, the aim should be to provide energy as close
as possible to the measured energy expenditure in order to decrease negative
energy balance. In the absence of indirect calorimetry, ICU patients should
receive 25 kcal/kg/day increasing to target over the next 2–3 days.
Supplementar All patients receiving less than their targeted enteral feeding after 2 days

y should be considered for supplementary PN.

PN with EN
Carbohydrates The minimal amount of carbohydrate required is about 2 g/kg of glucose per
day. Hyperglycemia (glucose>10 mmol/L) contributes to death in the critically
ill patient and should also be avoided to prevent infectious complications.
Reductions and increases in mortality rates have been reported in ICU patients
when blood glucose is maintained between 4.5 and 6.1 mmol/L. No
unequivocal recommendation on this is therefore possible at present. There is a
higher incidence of severe hypoglycemia in patients treated to the tighter
limits.
Lipids Lipids should be an integral part of PN for energy and to ensure essential fatty
acid provision in long-term ICU patients. Intravenous lipid emulsions (LCT, MCT
 or mixed emulsions) can be administered safely at a rate of 0.7 g/kg up to 1.5
g/kg over 12 to 24 h. The tolerance of mixed LCT/MCT lipid emulsions in
standard use is sufficiently documented.
Amino Acids When PN is indicated, a balanced amino acid mixture should be infused at
approximately 1.3–1.5 g/kg ideal body weight/day in conjunction with an
adequate energy supply. When PN is indicated in ICU patients the amino acid
solution should contain 0.2–0.4 g/kg/day of glutamine (e.g. 0.3–0.6 g/kg/day
alanyl-glutamine dipeptide)
Micronutrients All PN prescriptions should include a daily dose of multivitamins and of trace
elements.
Route A central venous access device is often required to administer the high
osmolarity PN mixture designed to cover the nutritional needs fully.
Peripheral venous access devices may be considered for low osmolarity (<850
mOsmol/L) mixtures designed to cover a proportion of the nutritional needs
and to mitigate negative energy balance. If peripherally administered PN does
not allow full provision of the patient’s needs then PN should be centrally
administered
Mode PN admixtures should be administered as a complete all-in-one bag
Figure 15. ESPEN Guidelines on Parenteral Nutrition 2009
Acid-Base Homeostasis
Normal acid- base balance depends on the cooperation of at least two vital organ
systems: the lungs and the kidneys. The gastrointestinal (GI) tract also is involved in many
acid-base disturbances. Multiorgan system involvement , therefore, provides the
backdrop for the acid- base disorders commonly seen in critically ill patients.

Normal Acid-Base Physiology

Normal biochemical and physiologic function requires that the extracellular pH
be maintained within a very narrow range. Although the “normal” range of pH in
clinical laboratories is 7.35 to 7.45 pH units, the actual pH in vivo varies considerably
less. This tight control is maintained by a complex homeostatic mechanism involving
buffers and the elimination of volatile acid by respiration. The principal extracellular buffer
system is the carbonic acid/bicarbonate pair. The equilibrium relationships of the
components of this system are illustrated as follows:

From these relationships, the Henderson-Hasselbalch equation is derived:

In this equation, αCO2 is the solubility coefficient of CO2 (0.03), and pK is the
equilibrium constant for this buffer pair. Rearrangement yields the Henderson equation:

It is apparent from this equation that disturbances in the proton

concentration of the extracellular fluid (ECF) (and blood) may be due to perturbation
in the numerator, the denominator, or both. Disturbances that affect the PCO2
primarily are called respiratory disturbances, and those that affect the HCO3−primarily are
called metabolic. Acid- base homeostasis depends on compensation for a primary
disturbance. Compensation for a respiratory disturbance is metabolic, and compensation
for a metabolic disturbance is respiratory. Furthermore, it is clear from the previous
equations that in order to mitigate the change in proton concentration or pH , the
direct ion of the compensation must be the same as the direct ion of the primary
disturbance. Thus, consumption of bicarbonate will be accompanied by
hyperventilation and a consequent reduction in PCO2. A simple acid- base disturbance is
considered to consist of the primary disturbance and its normal compensation. A
complex acid- base disturbance consists of more than one primary disturbance. In order
to detect complex acid- base disturbances, one must be familiar with both the
direction and magnitude of normal compensation (shown in Table below). More than
one metabolic disturbance may coexist (e.g., metabolic acidosis and metabolic
alkalosis), but only one respiratory disturbance is possible at a time.

Figure 16. Expected Compensation for Simple Acid-Base Disorders

Metabolic Acidosis
Definition and Classification
A metabolic acidosis is a process that , if unopposed, would cause acidemia (a
high hydrogen ion concentration, or low pH , of the blood) by reducing the
extracellular bicarbonate concentration. The extracellular bicarbonate concentration may
be reduced by either addition of acid and consequent consumption of bicarbonate, or
by primary loss of bicarbonate. An adult eating a normal diet generates 16,000 to
20,000 mmol of acid a day . Almost all of that acid is in the form of carbonic acid, resulting
from CO2 and water generation in the metabolism of carbohydrates and fats. Individuals
with normal ventilatory capacity eliminate this prodigious acid load through the lungs,
thus the term volatile acid. The remainder of the daily acid load, about 1 mmol/kg
body weight per day , derives from metabolism of phosphate- and sulfate rich protein
(yielding phosphoric and sulfuric acid). These nonvolatile or fixed acids are buffered,
primarily by extracellular bicarbonate under normal circumstances. The kidneys are
responsible for regenerating the consumed bicarbonate by secreting hydrogen ions
(protons) in the distal nephron. These secreted protons must be buffered in the tubule
lumen in order to allow elimination of the daily fixed acid load within the physiologic
constraint of the minimum urinary pH. The urinary buffers are composed of the filtered
sodium salts of the phosphoric acid and ammonia, which is synthesized in the
proximal tubule and acidified in the collecting duct to form ammonium (NH4+). Under
conditions of acid loading, the normal kidney reabsorbs all the filtered bicarbonate in
the proximal tubule. Urinary net acid excretion therefore comprises phosphoric acid
(so- called titratable acidity , because it is quantified by titrating the urine with alkali to
pH 7.40) and ammonium, less any excreted bicarbonate.
Many factors modify the kidney’s capacity to regulate acid- base balance. For
example, renal ammonia-genesis is stimulated by acidemia, and inhibited by alkalemia,
and thus participates in a homeostatic feedback loop. Hyperkalemia inhibits and
hypokalemia stimulates renal ammonia-genesis. Hypokalemia further stimulates acid
secretion by activating the Na+-H+exchanger in the proximal tubule and the H+/K+-
ATPase in the collecting duct. Finally, aldosterone stimulates both proton and K+ secret
ion in the collecting duct. For these reasons, hypokalemia tends to perpetuate a metabolic
alkalosis, and hyperkalemia a metabolic acidosis. Metabolic acidosis can be caused by
excessive product ion of fixed acid, decreased renal secret ion of fixed acid, or loss of
bicarbonate, either through the kidney or through the intestine. The net effect of any of
these processes is a reduction in the blood bicarbonate concentration. The plasma anion
gap helps to distinguish among the various causes of metabolic acidosis. Of course,
because of charge neutrality , the sum of the concentration of all cat ions in the
plasma is equal to the sum of all the anions. By convent ion, however, the anion gap is
defined as the difference between the plasma sodium concentration and the sum of the
bicarbonate and chloride concentrations. It represents the concentration of anions that
are normally unmeasured by a basic metabolic chemistry panel. The anion gap normally is
about 8 mmol/L, but it varies widely according to the methods employed by the clinical
chemistry laboratory. The anion gap is composed mainly of albumin, along with
phosphates, sulfates, and organic anions. There are two important pit falls in the
interpretation of the anion gap. First , because the anion gap is proportional to the
plasma albumin concentration, hypoalbuminemia (common in critically ill patients) will
lower the “baseline” anion gap (by approximately 2.5 mmol/L for each g/dL decline
in the albumin concentration). Thus, profound hypoalbuminemia may falsely lower the
anion gap, and thus mask a high anion gap acidosis. Second, alkalemia increases the
anion gap by causing lactate generation and by titrating plasma buffers, most notably
albumin. (Thus, in respiratory alkalosis, the bicarbonate concentration will be low in
compensation, and the anion gap may be elevated, giving a false impression of a
high anion gap metabolic acidosis by inspect ion of the electrolytes alone.) If
bicarbonate is lost (e.g., through diarrhea), or hydrochloric acid is gained (e.g., renal
tubular acidosis or administration of unbuffered amino acid solutions), the bicarbonate
concentration falls with a commensurate increase in the plasma chloride
concentration; thus the anion gap is unchanged. If, on the other hand, bicarbonate is
lost in buffering an organic acid such as lactic acid or a ketoacid, the decrement in
the bicarbonate concentration is more or less matched by an increase in the anion
gap. These processes are illustrated in Figure below. (The generation of hyperchloremic and
anion gap (AG) acidoses. Blocks represent the ionic composition of the plasma, cations (+) to
the left and anions (−) to the right. In each of the panels (A and B), the bar to the left
represents the basal or normal state. The AG is shown in red. A, The change in the ionic
composition of the plasma when hydrochloric acid is added. The chloride concentration
increases as bicarbonate is consumed. B, The effect of addition of an organic acid such as
lactic acid, in which case the bicarbonate is consumed and the AG increases proportionately.
Cl, chloride; H2CO3, carbonic acid; Na, sodium; NaHCO3, sodium bicarbonate.)
Figure 17. Anion Gap.

Table on fig.18 lists the causes of hyperchloremic metabolic acidosis. Two diagnoses
are of particular interest in the critical care arena. First is the posthypocapnic metabolic
acidosis, in which bicarbonate falls in compensation for a chronic respiratory alkalosis. When
“normal” ventilation is restored, the pH falls until bicarbonate can be retained, giving
the appearance of a hyperchloremic metabolic acidosis. This emphasizes the importance
of observation over time in the analysis of acid-base status. The second entity of interest is
a so-called dilutional hyperchloremic acidosis. This is seen in patients who are rapidly
resuscitated with large volumes of isotonic saline solution. The acidosis traditionally has
been attributed to dilution of blood bicarbonate. Analysis based on physical-chemistry
principles may better explain the phenomenon (see later).

Causes of Hyperchloremic Metabolic Acidosis

Extrarenal Loss of Base:
 Diarrhea
 Pancreatic fistula
 Ureteral diversion
Extrarenal Gain of Acid:
 Ammonium chloride
 Hydrochloric acid
 Sodium chloride
 Renal Loss of Base:
 Type II renal tubular acidosis
 Posthypocapnic state
 Excretion of organic anions (bicarbonate precursors)
 Toluene inhalation (glue sniffing)
 Diabetic ketoacidosis
Renal Acid Excretory Defect:
 Type IV renal tubular acidosis
 Chronic kidney disease
 Hypoaldosteronism
 Urinary tract obstruction
 Type I renal tubular acidosis
 Sickle cell nephropathy
 Lupus nephritis
 Renal transplant

The differential diagnosis of high anion gap metabolic acidosis is limited (Box
57.2 ). The most common cause in critically ill patients is a lactic acidosis. The causes of
lactic acidosis are numerous. As shown in Box 57.3 , they are divided into type A
(imbalance between tissue oxygen demand and supply) and type B (impaired oxygen
utilization). Diabetic ketoacidosis (DKA) and intoxications (Chapter 68) are discussed
elsewhere. Two causes of high anion gap acidosis recently added to the differential
diagnosis, and of particular relevance to intensivist, are pyro glutamic acidosis and
intoxication with propylene glycol.
Cause of High Anion Gap Metabolic Acidosis:
 Ketoacidosis
o Diabetic
o Alcoholic
o Starvation
 Intoxications
o Methanol
o Ethylene glycol
 o Propylene glycol
o Salicylate
o Pyro glutamic acidosis
 Lactic acidosis (see later)
 Uremic acidosis

Causes of Lactic Acidosis

Type A (Tissue Oxygen Supply : Demand Mismatch)
Decreased tissue oxygen delivery
 Shock
 Hypoxemia
 Severe anemia
 Carb on monoxide poisoning
Increased tissue oxygen demand
 Grand mal seizure
 Extreme exercise
Type B (Impaired Tissue Oxygen Utilization)
 Sepsis/systemic inflammatory response syndrome
 Diabetes mellitus
 Malignancy
 Thiamine deficiency
 Inborn errors of metabolism
 Human immunodeficiency virus infection
 Malaria
 Drugs/toxins: Ethanol, Metformin, Zidovudine, Didanosine, Stavudine, Lamivudine,
Zalcitabine, Salicylate, Propofol, Niacin, Isoniazid, Nitroprusside, Cyanide,
Catecholamines, Cocaine, Acetaminophen, Streptozotocin, Sorbitol/fructose,
Carboplatin, Entecavir, Linezolid
 Liver failure

Pyro glutamic acid is a metabolic intermediate in the γ- glutamyl cycle, one product of
which is glutathione. Pyroglutamic acidosis may be congenital (caused by one of
several enzyme deficiencies) or acquired. The acquired syndrome may be caused by
acetaminophen (which depletes glutathione, leading to uninhibited pyroglutamic acid
synthesis), β- lactam antibiotics, or glycine deficiency . The acidosis may be profound
and the anion gap greater than 30 mmol/L. Definitive diagnosis is made by urinary
screen for organic acids. In practice, however, circumstantial evidence suggests the
acquired syndrome and the diagnosis is supported by a favorable response to
appropriate intervention. Propylene glycol is a solvent for medications, many of which
are commonly infused intravenously in critically ill patients, such as lorazepam,
nitroglycerin, etomidate, and phenytoin. Propylene glycol is metabolized by alcohol-
dehydrogenase to lactic acid. High anion gap acidosis has been associated with high-
and even low - dose infusions, particularly of lorazepam. Thus, development of a high
anion gap acidosis in a critically ill patient should prompt a search for a source of
propylene glycol, because withdrawal of the agent ill promptly alleviate the acidosis.

Consequences of Acidemia
It has been generally accepted that severe acidemia (pH < 7.20) is associated with
a variety of deleterious effects. Of particular concern are the cardiovascular effects,
including pressure- resistant arterial vasodilation, venoconstriction, diminished
myocardial contractility , and impaired hepatic and renal perfusion. (Some controversy
exists as to which of these effects are directly caused by acidemia.) A predisposition
to malignant arrhythmias has been reported in vitro and in animal models. Finally,
numerous metabolic derangements have been attributed to the effect of acidemia on
key enzymes in metabolic pathways, resulting in sympathetic hyperactivity with
diminished catecholamine responsiveness; insulin resistance and suppressed glycolysis; and
reduced hepatic lactic acid uptake and metabolism.

Treatment of Metabolic Acidosis

Treatment of metabolic acidosis is aimed at reversing the adverse
consequences of acidemia. Treatment of hyperchloremic metabolic acidosis is
straightforward. In cases of acute metabolic acidosis, treatment depends on successful
therapy of the underlying cause (e.g., diarrhea) and correct ion of the bicarbonate
deficit , usually in the form of sodium bicarbonate. One can estimate the bicarbonate
deficit as follows:
The difficulty in accurately estimating this value arises from two factors: First , the
apparent volume of distribution of bicarbonate varies more than two fold  from 50%
of body weight to 100% of body weight   and is inversely proportional to the initial
bicarbonate concentration. Second, there are often many simultaneous processes in a
critically ill patient that tend to ameliorate or ex acerb ate the metabolic acidosis,
such as vomiting, shock, and liver failure. In order to avoid overshoot alkalemia, it is
prudent to estimate the volume of distribution to be 50% of the body w eight and to
target an increase in the bicarbonate concentration of no more than 8 mmol/L over 12 to
24 hours. Sodium bicarbonate generally is considered to be the alkalinizing agent of
choice for severe acidemia. Alternative alkalinizing agents such as citrate, acetate, and
lactate, which under normal circumstances are oxidized in the liver to bicarbonate, should
not be used to treat acidemia in patients with suspected or confirmed hepatic
impairment or circulatory compromise. The sodium bicarbonate should be administered
as a continuous infusion, the concentration of which should be guided by the patient's
serum sodium concentration. Bolus inject ion of undiluted ampules of sodium bicarbonate
(1000 mmol/L) should be used with great restraint and only in patients with the
most severe acidemia because of the risk of hyperosmolality. Large volumes of any
bicarbonate solution can lead to volume overload, a reduction in the ionized calcium
concentration and increased generation of CO2. This last effect will tend to cause a
respiratory acidosis in patients with ventilatory insufficiency . Plasma electrolytes and
blood gases must be monitored frequently to guide adjustments in the composition of
the solution and its rate of infusion. Tris (hydroxymethyl) aminomethane, or THAM, is an
amino alcohol that buffers without generating CO2. I t has the advantage, therefore, of
avoiding a superimposed respiratory acidosis. It has been used successfully in animals
and humans with various metabolic acidoses. It is eliminated by the kidney , and thus
should be used with caution in the setting of renal insufficiency . Risks include
hyperkalemia, hypoglycemia, and hepatic necrosis (in neonates). The treatment of choice
for lactic acidosis is reversal of the underlying cause of the acidosis. Pending
resolution of the underlying disorder, however, the intensivist is often confronted with
an unstable patient who is profoundly acidemic. Treatment at this stage is
controversial. The debate has focused on the potentially deleterious effects of
bicarbonate administration in lactic acidosis. In addition to the effects mentioned
earlier , bicarbonate in animal models of lactic acidosis has been associated with
increased lactate generation, reduction in intracellular pH , increased venous PCO2 ,
and reduction in cardiac output .

Metabolic Alkalosis
Definition and Classification
Metabolic alkalosis is a process leading to accumulation of extracellular bicarbonate that, if
unopposed, will result in an increase in the plasma pH (alkalemia). It can be caused either
by a gain of bicarbonate or a loss of fixed acid from the ECF . The causes of
metabolic alkalosis have been described. In its pure form, it is accompanied by
hypoventilation (CO2 -retention). From a pathophysiologic perspective, metabolic
alkalosis is divided into those factors that generate the alkalosis and those factors that
maintain or perpetuate it. Metabolic alkalosis is generated by addition of bicarbonate to
the blood. This can occur either by loss of acid from the body or by addition of
exogenous alkali. Loss of acid may be from the stomach (e.g., vomiting or nasogastric
suction) or kidney. Renal acid loss is enhanced by a high rate of sodium delivery to the
distal nephron, high circulating mineralocorticoid levels, potassium depletion, and high
rates of ammoniagenesis. Because of the kidney 's prodigious ability to excrete
bicarbonate, however, addition of bicarbonate to the blood is not sufficient to cause
a sustained metabolic alkalosis. Some mechanism(s) to maintain the alkalosis must prevail.
The most common mechanism contributing to the maintenance of metabolic alkalosis is
volume depletion, either absolute or relative (e.g., congestive heart failure), which (1)
reduces glomerular filtration, (2) enhances tubular bicarbonate reabsorption, and (3)
causes secondary hyperaldosteronism, further enhancing urinary acidification. Another
common perpetuating factor is potassium depletion, which stimulates proton secretion
at several sites along the nephron. Patients with metabolic alkalosis and signs of
volume expansion—especially hypertension—usually have excess mineralocorticoid as
the explanation for the metabolic alkalosis. Aldosterone and glucocorticoids (other than
dexamethasone) stimulate renal loss of acid and potassium, and thereby generate and
maintain the alkalosis. Most cases of clinically significant metabolic alkalosis are
maintained by loss of chloride or potassium. Although total body sodium (and hence,
volume) derangements are not directly responsible for the generation and
maintenance of the metabolic alkalosis, potassium and chloride depletion are
commonly seen in settings of volume depletion or excess. Therefore, from a clinical
standpoint , it is useful to approach the patient with metabolic alkalosis centering on
the history and physical examination, with special attention to the ECF volume status,
followed by sequential analysis of blood chemistries.
Causes of Metabolic Alkalosis
Intravascular Volume Depletion, Absolute or “Effective”
Gastrointestinal acid loss (vomiting or nasogastric suction, Villous adenoma, chloride diarrhea)
Renal acid loss (diuretics (loop, thiazide), Bartter syndrome, Gitelman syndrome)
Magnesium depletion
Posthypercapnic state
Congestive heart failure
Hepatic cirrhosis/ascites
Intravascular Volume Expansion
Renal artery stenosis
Accelerated hypertension
Renin- secreting tumor
Primary aldosteronism
Cushing syndrome or disease
Exogenous mineralocorticoid
Apparent mineralocorticoid excess syndrome
Liddle syndrome
Renal insufficiency
Exogenous alkali load
Milk- alkali syndrome

One entity unique to critically ill patients is posthypercapnic metabolic alkalosis. This
syndrome is caused by abrupt treatment (usually with tracheal intubation and
mechanical ventilation) of a chronic respiratory acidosis. The renal bicarbonate
retention that compensated for the chronic respiratory acidosis persists (because of
volume depletion) after restoration of a normal PCO2, resulting in the high pH and
high plasma bicarbonate characteristic of metabolic alkalosis. The key to the diagnosis is
the history and sequential analysis of blood chemistries.

Clinical Consequences
Alkalemia in critically ill patients is associated with increased mortality rate.
Patients with combined metabolic and respiratory alkalosis have a higher mortality
rate than those with respiratory alkalosis alone, and mortality rate in alkalemia is
roughly proportional to the pH. Although no causal relationship between alkalemia and
mortality rate has been established, the pathophysiology of alkalemia is far from
benign. First, metabolic alkalosis suppresses ventilation, causing CO2 retention and relative
hypoxemia. Second, alkalemia acutely increases hemoglobin's oxygen affinity (Bohr effect).
Third, respiratory alkalosis causes vasoconstriction, particularly in the cerebral circulation.
All these processes tend to decrease tissue oxygen delivery. (Note that chronic alkalemia
inhibits 2,3- di-phospho-glycerate synthesis, allowing normalization of the
oxyhemoglobin desaturation curve, mitigating tissue hypoxia to some extent.) These
alterations in tissue oxygen delivery could be responsible at least in part for some
of the clinical manifestations of metabolic alkalosis. Because alkalemia causes a decrease
in ionized calcium concentration , many of the neuromuscular manifestations of
metabolic alkalosis overlap with those of hypocalcemia, including paresthesias, tetany,
and a predisposition to seizures. The acutely diminished tissue oxygen delivery to the brain
may contribute to initial confusion and obtundation seen with metabolic alkalosis. Metabolic
alkalosis often is accompanied by hypokalemia and hypomagnesemia. Thus, there is an
association between alkalosis and arrhythmias, but an independent effect of the alkalosis
on cardiac arrythmogenesis has not been established. Increases in blood lactate
concentration may occur in patients with metabolic alkalosis due to up-regulation of
phosphofructokinase and thus glycolysis, and because of tissue hypoxia (see earlier ).
With severe metabolic alkalosis (arterial pH above 7.55), the tissue hypoxia may be
so marked that compensatory hypoventilation will be overridden by hypoxic drive,
resulting in a normal to low arterial PCO2 and elevated blood lactate levels (so- called
“lactic alkalosis”).

Treatment
Treatment of metabolic alkalosis entails correcting the factor(s) responsible for its
maintenance and, if possible, correcting the factor that generated the alkalosis. Once
the underlying diagnosis is clear, therapy is usually straightforward. If the metabolic
alkalosis is maintained by chloride depletion and ECF volume contract ion, the
intravascular volume should be restored to normal, usually with intravenous isotonic
saline. Potassium should be given, as KCl, to replace any deficits , because potassium
depletion perpetuates the metabolic alkalosis. If nasogastric suction cannot be stopped,
acid loss can be reduced by the use of H2b lockers and proton pump inhibitors. Treating
patients with metabolic alkalosis in the setting of volume overload and diminished
effective circulating volume (e.g., congest iv e heart failure, hepatic cirrhosis) is more
challenging, because saline infusion is contraindicated. Unless hyperkalemia is present ,
chloride should be replenished with KCl supplementation. In rare cases of concurrent
hyperkalemia, acetazolamide (a carbonic anydrase inhibitor) may be of benefit as it
produces a bicarbonate diuresis. Acetazolamide should be avoided in patients with
hypokalemia, because the alkaline diuresis will cause renal potassium wasting. Another
potential complication of acetazolamide administration, particularly in patients with
impending ventilatory failure, is worsening of hypercapnia owing to inhibition of red
blood cell carbonic anhydrase and impaired CO2 transport. Hydrochloric acid infusion,
as a 0.1 to 0.25 N solution, has been used with success in patients with severe
metabolic alkalosis (pH > 7.55 and systemic instability such as encephalopathy or
cardiac arrhythmia) refractory to conventional measures. Correct ion of the metabolic
disturbances has been reported with infusion of 0.25N HCl at 100 mL /hour over about 12
hours. Extreme care must be taken to ensure that the infusion catheter is properly
positioned within the vena cava, because the solution is highly caustic. Plasma
chemistries must be monitored frequently in order to avoid overcorrection. If renal
function is severely impaired or medical therapy is not possible, hemodialysis against
a low - bicarbonate bath may be used. In states of primary mineralocorticoid excess, an
aldosterone antagonist such as spironolactone should be used until the underlying
abnormality can be corrected. Other potassium- sparing diuretics, such as amiloride
and triamterene, are useful as well and are essential in managing the rare patient with
Liddle syndrome.

Respiratory acidosis
Respiratory acidosis is defined as a primary increase in PaCO2. This increase drives the
reaction

to the right, leading to an increase in [H+] and a decrease in arterial pH. For the reasons
described above, [HCO3−] is minimally affected. PaCO2 represents the balance between CO2
production and CO2 elimination:
 CO2 is a byproduct of fat and carbohydrate metabolism. Muscle activity, body
temperature, and thyroid hormone activity can all have major influences on CO2 production.
Because CO2 production does not appreciably vary under most circumstances, respiratory
acidosis is usually the result of alveolar hypoventilation (see Table). In patients with a limited
capacity to increase alveolar ventilation, however, increased CO2 production can precipitate
respiratory acidosis.

Acute Respiratory Acidosis

The compensatory response to acute (6–12 h) elevations in PaCO2 is limited.
Buffering is primarily provided by hemoglobin and the exchange of extracellular H+ for Na+
and K+ from bone and the intracellular fluid compartment. The renal response to retain
more bicarbonate is acutely very limited. As a result, plasma [HCO3−] increases only about 1
mEq/L for each 10 mm Hg increase in PaCO2 above 40 mm Hg.

Chronic Respiratory Acidosis

“Full” renal compensation characterizes chronic respiratory acidosis. Renal
compensation is appreciable only after 12–24 hr and may not peak until 3–5 days. During
that time, the sustained increase in PaCO2 has been present long enough to permit maximal
renal compensation. During chronic respiratory acidosis, plasma [HCO3−] increases
approximately 4 mEq/L for each 10 mm Hg increase in PaCO2 above 40 mm Hg.

Treatment of Respiratory Acidosis

Respiratory acidosis is treated by reversing the imbalance between CO2 production and
alveolar ventilation. In most instances, this is accomplished by increasing alveolar
ventilation. Measures aimed at reducing CO2 production are useful only in specific instances
(eg, dantrolene for malignant hyperthermia, muscle paralysis for tetanus, antithyroid
medication for thyroid storm, and reduced caloric intake in patients receiving enteral or
parenteral nutrition). Potential temporizing measures aimed at improving alveolar
ventilation (in addition to controlled mechanical ventilation) include bronchodilation,
reversal of narcosis, or improving lung compliance (diuresis). Severe acidosis (pH <7.20), CO2
narcosis, and respiratory muscle fatigue are indications for mechanical ventilation. An
increased inspired oxygen concentration is also usually necessary, as coexistent hypoxemia is
common. Intravenous NaHCO3 is rarely necessary, unless pH is <7.10 and HCO3− is <15
mEq/L. Sodium bicarbonate therapy will transiently increase PaCO2:
 Buffers that do not produce CO2, such as Carbicarb TM or tromethamine (THAM), are
theoretically attractive alternatives; however, there is almost no evidence showing that they
have greater efficacy than bicarbonate. Carbicarb TM is a mixture of 0.3 M sodium
bicarbonate and 0.3 M sodium carbonate; buffering by this mixture mainly produces sodium
bicarbonate instead of CO2. Tromethamine has the added advantage of lacking sodium and
may be a more effective intracellular buffer. Patients with a baseline chronic respiratory
acidosis require special consideration. When such patients develop acute ventilatory failure,
the goal of therapy should be to return PaCO2 to the patient’s “normal” baseline.
Normalizing the patient’s PaCO2 to 40 mm Hg will produces the equivalent of a respiratory
alkalosis. Oxygen therapy must also be carefully controlled, because the respiratory drive in
these patients may be dependent on hypoxemia, not PaCO2. “Normalization” of PaCO2 or
relative hyperoxia can precipitate severe hypoventilation.

Causes of respiratory acidosis

Alveolar hypoventilation
 Central nervous system depression
o Drug-induced
o Sleep disorders
o Obesity hypoventilation (Pickwickian) syndrome
o Cerebral ischemia
o Cerebral trauma
 Neuromuscular disorders
o Myopathies
o Neuropathies
 Chest wall abnormalities
o Flail chest
o Kyphoscoliosis
 Pleural abnormalities
o Pneumothorax
o Pleural effusion
 Airway obstruction
 o Upper airway
 Foreign body
 Tumor
 Laryngospasm
 Sleep disorders
o Lower airway
 Severe asthma
 Chronic obstructive pulmonary disease
 Tumor
 Parenchymal lung disease
o Pulmonary edema
 Cardiogenic
 Noncardiogenic
o Pulmonary emboli
o Pneumonia
o Aspiration
o Interstitial lung disease
 Ventilator malfunction
Increased CO2 production
 Large caloric loads
 Malignant hyperthermia
 Intensive shivering
 Prolonged seizure activity
 Thyroid storm
 Extensive thermal injury (burns)

Respiratory alkalosis
Respiratory alkalosis is defined as a primary decrease in PaCO2. The mechanism is
usually an inappropriate increase in alveolar ventilation relative to CO2 production. Plasma
[HCO 3−] usually decreases 2 mEq/L for each 10 mm Hg acute decrease in PaCO2 below 40
mm Hg. The distinction between acute and chronic respiratory alkalosis is not always made,
because the compensatory response to chronic respiratory alkalosis is quite variable: plasma
[HCO3−] decreases 2–5 mEq/L for each 10 mm Hg decrease in PaCO2 below 40 mm Hg.
Treatment of Respiratory Alkalosis
Correction of the underlying process is the only treatment for respiratory alkalosis.
For severe alkalemia (arterial pH >7.60), intravenous hydrochloric acid, arginine chloride, or
ammonium chloride may be indicated.

Causes of Respiratory Alkalosis

Central stimulation
 Pain
 Anxiety
 Ischemia
 Stroke
 Tumor
 Infection
 Fever
 Drug-induced
 Salicylates
 Progesterone (pregnancy)
 Analeptics (doxapram)
Peripheral stimulation
 Hypoxemia
 High altitude
 Pulmonary disease
o Congestive heart failure
o Noncardiogenic pulmonary edema
o Asthma
o Pulmonary embolism
 Severe anemia
Unknown mechanism
 Sepsis
 Metabolic encephalopathies
Iatrogenic
 Ventilator-induced
Figure 18. Causes of Respiratory Alkalosis
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