Anesthetics Inhalation : SEVOFLURANE

Physical Properties Like desflurane, sevoflurane is halogenated with fluorine. Sevoflurane’s solubility
in blood is slightly greater than desflurane (λb/g 0.65 versus 0.42) (see Table 8–1). Nonpungency and
rapid increases in alveolar anesthetic concentration make sevoflurane an excellent choice for
smooth and rapid inhalation inductions in pediatric and adult patients. In fact, inhalation induction
with 4% to 8% sevoflurane in a 50% mixture of nitrous oxide and oxygen can be achieved within 1
min. Likewise, its low blood solubility results in a rapid fall in alveolar anesthetic concentration upon
discontinuation and a more rapid emergence compared with isoflurane (although not an earlier
discharge from the postanesthesia care unit). Sevoflurane’s modest vapor pressure permits the use
of a conventional variable bypass vaporizer. Effects on Organ Systems A. Cardiovascular Sevoflurane
mildly depresses myocardial contractility. Systemic vascular resistance and arterial blood pressure
decline slightly less than with isoflurane or desflurane. Because sevoflurane causes little, if any, rise
in heart rate, cardiacoutput is not maintained as well as with isoflurane or desflurane. Sevoflurane
may prolong the QT interval, the clinical significance of which is unknown. QT prolongation may be
manifest 60 min following anesthetic emergence in infants. B. Respiratory Sevoflurane depresses
respiration and reverses bronchospasm to an extent similar to that of isoflurane. C. Cerebral Similar
to isoflurane and desflurane, sevoflurane causes slight increases in CBF and intracranial pressure at
normocarbia, although some studies show a decrease in CBF. High concentrations of sevoflurane
(>1.5 MAC) may impair autoregulation of CBF, thus allowing a drop in CBF during hemorrhagic
hypotension. This effect on CBF autoregulation seems to be less pronounced than with isoflurane.
Cerebral metabolic oxygen requirements decrease, and seizure activity has not been reported. D.
Neuromuscular Sevoflurane produces adequate muscle relaxation for intubation following an
inhalation induction, although most practitioners will deepen anesthesia with various combinations
of propofol, lidocaine, or opioids; administer a neuromuscular blocker prior to intubation; or a
combination of these two approaches. E. Renal Sevoflurane slightly decreases renal blood flow. Its
metabolism to substances associated with impaired renal tubule function (eg, decreased
concentrating ability) is discussed below. F. Hepatic Sevoflurane decreases portal vein blood flow,
but increases hepatic artery blood flow, thereby maintaining total hepatic blood flow and oxygen
delivery. It is generally not associated with immune-mediated anesthetic hepatotoxicity
Biotransformation & Toxicity The liver microsomal enzyme P-450 (specifically the 2E1 isoform)
metabolizessevoflurane at a rate one-fourth that of halothane (5% versus 20%), but 10 to 25 times
that of isoflurane or desflurane and may be induced with ethanol or phenobarbital pretreatment.
The potential nephrotoxicity of the resulting rise in inorganic fluoride (F − ) was discussed earlier.
Serum fluoride concentrations exceed 50 μmol/L in approximately 7% of patients who receive
sevoflurane, yet clinically significant kidney dysfunction has not been associated with sevoflurane
anesthesia. The overall rate of sevoflurane metabolism is 5%, or 10 times that of isoflurane.
Nonetheless, there has been no association with peak fluoride levels following sevoflurane and any
renal concentrating abnormality. Alkali such as barium hydroxide lime or soda lime (but not calcium
hydroxide) can degrade sevoflurane, producing another proven (at least in rats) nephrotoxic end
product (compound A, fluoromethyl-2,2-difluoro-1- [trifluoromethyl]vinyl ether). Accumulation of
compound A increases with increased respiratory gas temperature, low-flow anesthesia, dry barium
hydroxide absorbent (Baralyme), high sevoflurane concentrations, and anesthetics of long duration.
We are not aware of a study that has associated sevoflurane with any detectable postoperative renal
toxicity or injury. Nonetheless, some clinicians recommend that fresh gas flows be at least 2 L/min
for anesthetics lasting more than a few hours. Sevoflurane can also be degraded into hydrogen
fluoride by metal and environmental impurities present in manufacturing equipment, glass bottle
packaging, and anesthesia equipment. Hydrogen fluoride can produce an acid burn on contact with
respiratory mucosa. The risk of patient injury has been substantially reduced by inhibition of the
degradation process by adding water to sevoflurane during the manufacturing process and
packaging it in a special plastic container. Isolated incidents of fire in the respiratory circuits of
anesthesia machines with desiccated CO2 absorbent have been reported when sevoflurane was
used. Contraindications Contraindications include severe hypovolemia, susceptibility to malignant
hyperthermia, and intracranial hypertension. Drug Interactions Like other volatile anesthetics,
sevoflurane potentiates NMBAs. It does not sensitize the heart to catecholamine-induced
arrhythmias.