Anesthesia

Stages of Anesthesia (ExpertMD)

1. Analgesia
a. Patient is awake
b. Amnesia (anterograde) – no memory with regards to events after administering anesthetic
agents
2. Excitation and Delirium
a. Hyperactive – instability of vital signs, spasms, seizures, irregular RR
3. Surgical Anesthesia
a. Regular VS
b. Surgeon can start operation
4. Respiratory Depression
a. Depression of Medulla, cessation of heartbeat (cardiac arrest)

General Anesthesia
 Site of action: Central Nervous System
 Concentration is measured in partial pressure
 Potency is measured in MAC (Mean Alveolar Concentration); prevent movement in 50% of patients
 Onset of action depends on
o Blood gas coefficient (Ostwald coefficient); conc in blood vs conc in alveolar gas
 Whatever is in the lungs goes to the blood
 Whatever is in the blood goes to the brain
o Respiratory Rate
 Higher lipophilicity = higher ability to cross neuronal membrane = higher potency

Mechanism of Action

 Increase GABA (inhibitory)

 Decrease glutamate (excitatory)

ADRs:

 CNS depression
 Respiratory depression
 CV depression
 Smooth muscle relaxation = vasodilation = hypotension

Inhaled Anesthetics
 Isoflurane is the most potent of the volatile anesthetics in clinical use, desflurane is the least soluble,
and sevoflurane is the least irritating to the airways.
 Nitrous oxide (N2O) can expand a pneumothorax to double or triple its size in 10 to 30 minutes, and
washout of N2O can lower alveolar concentrations of oxygen and carbon dioxide, a phenomenon called
diffusion hypoxia.
  Sevoflurane is the most commonly used anesthetic in the pediatric population based on its relative lack
of pungency when inhaled and its relative speed of emergence. These beneficial attributes outweigh
the emergence agitation associated with the use of sevoflurane in pediatric patients.
 The vascular system delivers blood to three physiologic tissue groups: the vessel-rich group (VRG), the
muscle group, and the fat group. The VRG includes the brain, heart, kidney, liver, digestive tract, and
glandular tissues.
 The CNS tissues of the VRG are referred to as tissues of desired effect. The tissues of the muscle and
fat groups comprise the tissues of accumulation. Anesthetic is delivered most rapidly to the VRG
because of high blood flow

Halothane
 Hepatotoxic

All Fluranes are NEPHROTOXIC

But not contraindicated in renal patients

Methoxyflurane
 Slow onset but most potent

Isoflurane
 is a halogenated methyl ethyl ether that is a clear, nonflammable liquid at room temperature and has a
high degree of pungency.
 It is the most potent of the volatile anesthetics in clinical use, has great physical stability, and
undergoes essentially no deterioration during storage for up to 5 years or on exposure to sunlight.
 It has become the “gold standard” anesthetic since its introduction in the 1970s.
 There was a brief period of controversy concerning the use of isoflurane in patients with coronary
disease because of the possibility for coronary “steal” arising from the potent effects of isoflurane on
coronary vasodilation. In clinical use, however, this has been, at most, a rare occurrence.
 Contraindicated in patients with pheochromocytoma due to catecholamine release

Desflurane and Isoflurane BOTH CAUSE REFLEX TACHYCARDIA

Desflurane
 Desflurane is the most pungent of MAC-equivalent volatile anesthetics and, if administered via the
facemask, results in coughing, salivation, breath holding, and laryngospasm.
 Desflurane causes bronchoconstriction and is contraindicated in asthmatics
 is a fluorinated methyl ethyl ether that differs from isoflurane by just one atom:
 less potency (the minimum alveolar concentration [MAC] of desflurane is five times higher than
isoflurane).
 One of the advantages of desflurane is the near-absent metabolism to serum trifluoroacetate. This
makes immune-mediated hepatitis a rare occurrence.
 In extremely dry CO2 absorbers, desflurane (and to a lesser extent isoflurane, enflurane, and
sevoflurane) degrades to form carbon monoxide.
 Desflurane has the lowest blood:gas solubility of the potent volatile anesthetics; moreover, its fat
solubility is roughly half that of the other volatile anesthetics.
 Thus, desflurane requires less downward titration in long surgical procedures to achieve a rapid
emergence by virtue of decreased tissue saturation. This may be particularly advantageous in the
morbidly obese patient.4
  Desflurane has been associated with tachycardia and hypertension when used with minimal opioids
and, in select cases, myocardial ischemia when used in high concentrations or when rapidly increasing
the inspired concentration.

Sevoflurane
 is a sweet smelling, completely fluorinated methyl isopropyl ether.
 Its vapor pressure is roughly one-fourth that of desflurane and it can be used in a conventional
vaporizer.
 The blood:gas solubility of sevoflurane is second only to desflurane in terms of potent volatile
anesthetics.
 Sevoflurane is approximately half as potent as isoflurane, and some of the preservation of potency,
despite fluorination, is because of the bulky propyl side chain on the ether molecule.
 Its pleasant odor, lack of pungency, and potent bronchodilating characteristics make sevoflurane
administration via the facemask for induction of anesthesia in both children and adults a reasonable
alternative to IV anesthetics.
 Sevoflurane is half as potent a coronary vasodilator as isoflurane, but is 10 to 20 times more vulnerable
to metabolism than isoflurane.
 The metabolism of sevoflurane results in inorganic fluoride but has not been associated with renal
concentrating defects.
 Unlike other potent volatile anesthetics, sevoflurane is not metabolized to trifluoroacetate; rather, it is
metabolized to an acyl halide (hexafluoroisopropanol). This does not stimulate formation of antibodies
associated with hepatitis.

Xenon
 is an inert gas occurring naturally in air at 0.05 parts per million (ppm).
 Xenon has received considerable interest in the last few years because it has many characteristics
approaching those of an “ideal” inhaled anesthetic.
 It has a quick onset and offset, minimal effects on the cardiovascular and neural systems, and it is not a
trigger for malignant hyperthermia (MH).
 It is not a pollutant or an occupational hazard, and does not add to global warming or the greenhouse
gas effect.
 Its blood:gas partition coefficient is 0.115, and unlike the other potent volatile anesthetics (except
methoxyflurane), xenon provides some degree of analgesia.
 This action is likely due to N-Methyl-d-aspartate (NMDA) receptor inhibition. The MAC of xenon in
humans is 71%, which might prove to be a limitation.
 It is nonexplosive, nonpungent, and odorless, and thus can be inhaled with ease. In addition, it does not
produce significant myocardial depression or alter coronary blood flow.6 Because of its scarcity and
high cost related to extraction by fractional distillation of the atmosphere, its role as a replacement for
current lower cost anesthetics remains uncertain. It may have potential for neuroprotection in select
settings via its inhibitory action of the NMDA receptor glycine site.

Nitrous oxide
 Fast onset but least potent
 ADRs: coughing, respiratory irritation, laughing
  a sweet-smelling, nonflammable gas of low potency (MAC =104%), and is relatively insoluble in blood.
 It is most commonly administered as an anesthetic adjuvant in combination with opioids or volatile
anesthetics during the conduct of general anesthesia.
 Unlike the potent volatile anesthetics in clinical use, N2O does not produce significant skeletal muscle
relaxation, but it does have modest analgesic effects.
 Despite a long track record of use, controversy has surrounded N2O in four areas:
o its role in postoperative nausea and vomiting;
o its potential toxic effects on cell function via inactivation of vitamin B12;
o its adverse effects related to absorption and expansion into air-filled structures and bubbles;
o and lastly, its effect on embryonic development.
 The most valid and most clinically relevant concern is the ability of N2O to expand air-filled spaces
because of its greater solubility in blood compared to nitrogen. This might explain the increased
postoperative nausea and vomiting (PONV) associated with N2O use since closed gas spaces reside in
the middle ear and bowel. Other closed spaces may occur as a result of disease or surgery, such as a
pneumothorax.
o Seventy-five percent N2O can expand a pneumothorax to double or triple its size in 10 and 30
minutes, respectively.
o Air-filled cuffs of pulmonary artery catheters and endotracheal tubes also expand with the use of
N2O, possibly causing tissue damage via increased pressure in the pulmonary artery or
trachea, respectively.

IV Anesthetics and Adjuvants

 Faster onset because route is IV
 Used for the induction of anesthesia

Propofol
 Aka milk of amnesia
 Short acting, inc. GABA mediated inhibition
 ADR: CNS, CV depression, Metabolic Acidosis (PRIS)
 One of the most frequently used intravenous anesthetics on the market today (Fig. 19-5; Table 19-2).
 Its pharmacokinetic profile presents a desirable rapid onset, a predictable context-sensitive half-time,
and a rapid emergence from anesthesia.
 Additionally, a favorable side-effect profile and antiemetic property allow for a wide spectrum of uses,
including induction and maintenance of general anesthesia, intensive care unit (ICU) sedation, and as a
sedative-hypnotic in a variety of outpatient procedures.
 The lipid emulsion comes in a familiar milky white consistency, and can be stored at room temperature
without any significant degradation.
 Propofol is primarily metabolized by the liver, and subsequently its inactive and water-soluble
metabolites are excreted by the kidneys. A small amount of unmetabolized propofol is excreted in both
urine and feces, but that is considered negligible (<3%). Despite the primary mechanism of metabolism,
liver and kidney disease have not been noted to alter pharmacokinetics of propofol significantly.
 The mechanism by which the unconscious state is attained by induction doses of propofol is
complicated and not fully understood. Primarily, it occurs via enhancement of GABA inhibitory
pathways. Other neuroreceptors have been linked to propofol activity, including α-adrenergic receptors
and Nmethyl-D-aspartate (NMDA) receptors. Alteration of the central cholinergic transmission by
propofol may also play a role in achieving a state of unconsciousness.
 Initial low doses of propofol produce sedation, but at increased doses a state of paradoxical excitation
may occur, where a patient is disinhibited, has unpredictable movement, broken speech, and is not
 readily arousable. A further increase in dose of propofol leads to loss of consciousness, apnea, relative
relaxation of muscles, loss of brainstem reflexes, and subsequently necessitates airway support.
 Similar to other intravenous anesthetics, the changes in electroencephalogram (EEG) pattern with
propofol are dependent on the depth of anesthesia achieved. At lower sedative doses, a characteristic
increase in β-wave activity is common. After an induction dose, initial stages of general anesthesia are
reached, and the EEG pattern often resembles that of deep non-REM sleep, with progressively
increased low-frequency and high-amplitude activity. This ultimately means that β-wave activity
decreases, with a simultaneous increase in α and δ activity.
 Propofol has specific antioxidant properties, and its function as a free radical scavenger has been
hypothesized to play a role in preventing injury during neurodegenerative processes such as stroke and
trauma. Other protective mechanisms have been hypothesized, including attenuation of excitotoxic
glutamate pathways that lower the likelihood of programmed neuronal apoptosis, and its overall anti-
inflammatory effects (e.g., decreasing TNF-α).
 Propofol is generally considered an anticonvulsant
 The loss of consciousness attributed to propofol can be partially reversed
 by the central cholinomimetic properties of physostigmine.21 This drug has
 been used in the treatment of emergence delirium, and presumably the
 mechanism of propofol reversal is similar.

Thiopental
 Barbiturate (Enhance GABA mediated Chloride channel opening; prolongs duration; Barbidurate)

Midazolam
 Increase the frequency of opening of GABA mediated chloride channel

Ketamine
 Only Anesthetic agent that is a CV STIMULANT (Hypertension)
 NMDA Antagonist
 Dissociative anesthesia

What is Malignant Hyperthermia?

 Bizarre ADR
 Not dose related
 High fever, rigidity of muscles, acidosis
 Trigger: All anesthetics esp succinylcholine
o Exception: Xenon
 Dantrolene (muscle relaxant); calcium channel blocker; antidote for MH

Board Exam Recalls

 Droperidol + Fentanyl = Neuroleptanalgesia

 Droperidol + Fentanyl + NO2 = Neuroleptanesthesia
Local Anesthetics
Physiology of Sensation

 Sensation is an ascending pathway

 Smaller fiber diameter = faster blocking