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Chapter: Clinical Anesthesiology: Clinical Pharmacology: Pharmacological Principles

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Sevoflurane - Clinical Pharmacology of Inhalation Anesthetics

Like desflurane, sevoflurane is halogenated with fluorine. Sevoflurane’s solubility in blood is sligh-tly greater than desflurane (λb/g 0.65 versus 0.42).

SEVOFLURANE

Physical Properties

Like desflurane, sevoflurane is halogenated with fluorine. Sevoflurane’s solubility in blood is sligh-tly greater than desflurane (λb/g 0.65 versus 0.42) (see Table 8–3). 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 dis-continuation and a more rapid emergence com-pared with isoflurane (although not an earlier discharge from the post-anesthesia care unit). Sevoflurane’s modest vapor pressure permits the use of a conventional variable bypass vaporizer.


Eects on Organ Systems

A. Cardiovascular

Sevoflurane mildly depresses myocardial contractil-ity. 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, cardiac output is not maintained as well as with isoflurane or desflurane. Sevoflurane may prolong the QT interval, the clinical signifi-cance 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 cerebral blood flow. High con-centrations 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 of children following an inhalation induction.

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 main-taining 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) metabolizes sevoflurane 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 pretreat-ment. 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 sevoflu-rane, yet clinically significant renal 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, flu-oromethyl-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.

Most studies have not associated sevoflurane with any detectable postoperative impairment of renal function that would indicate toxicity or injury. Nonetheless, some clinicians recommend that fresh gas flows be at least 2 L/min for anesthet-ics lasting more than a few hours and that sevoflu-rane not be used in patients with preexisting renal dysfunction. Sevoflurane can also be degraded into hydro-gen 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 deg-radation process by adding water to sevoflurane during the manufacturing process and packaging it in a special plastic container. The manufacturer has also distributed a “Dear Provider” letter warning of isolated incidents of fire in the respiratory circuits of anesthesia machines with desiccated CO2 absorbent when sevoflurane was used.

Contraindications

Contraindications include severe hypovolemia, sus-ceptibility to malignant hyperthermia, and intracra-nial hypertension.

Drug Interactions

Like other volatile anesthetics, sevoflurane potenti-ates NMBAs. It does not sensitize the heart to cate-cholamine-induced arrhythmias.

 

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