MAC values of sevoflurane decrease with age, from 3.3% in neonates and 2.5% in infants and young adults to 1.58% to 2.05% in middle-aged adults and 1.45% in adults who are more than 70 years old ^{26– 31} . In the presence of 65% nitrous oxide in the inspired gas mixture, MAC values for sevoflurane decrease by about 50% in adults ³² .

Gender does not influence the MAC of sevoflurane, but there is some evidence suggesting that ethnic factors may play a role: MAC values reported in US studies were consistently higher (2.05% to 2.6%) ^{5, 32} than those reported for Japanese adults (1.58% to 1.71%) ^{30, 31} .

As for the volatile anesthetic uptake, distribution and elimination are best described by a five-compartment mammillary model ³³ . This model consists of the lungs, the vessel-rich group of organs, muscle, fat adjacent to the vessel-rich organs, and peripheral fat. In general, an inverse relationship exists between the blood/gas partition coefficient of a volatile anesthetic and the time required for the inspired and alveolar concentrations to reach equilibrium. Sevoflurane has a low blood/gas partition coefficient (0.69), resulting in a swifter equilibration of the alveolar-to-inspiratory fraction (F _A/F _I ratio) than with enflurane and isoflurane but slightly slower than with nitrous oxide and desflurane ^{33, 34} .

Because of its pleasant odor and the absence of irritation to the airways, sevoflurane can be used for inhalational induction both in children and in adults ³⁵ . Studies have shown that induction is as rapid as ^{36, 37} or even swifter than ^{38– 40} with halothane.

Elimination of a volatile anesthetic is also related to its blood solubility. Between 95% and 98% of sevoflurane is eliminated through the lung. The driving force for this elimination is the difference in partial pressures between the inspired gas mix and the pulmonary capillary blood. In humans, 2% to 5% of the absorbed dose of sevoflurane is metabolized by the liver, resulting in the formation of inorganic fluoride and the organic fluoride metabolite hexafluoroisopropanol ⁴¹ . The latter is conjugated with glucuronic acid and excreted rapidly via the kidneys. The biotransformation of sevoflurane occurs predominantly through cytochrome P450(CYP)2E1 ^{42, 43} . Serum inorganic fluoride concentrations after sevoflurane anesthesia are dose-dependent, reaching 10 to 20 µmol/L after 1 to 2 MAC hours and up to 20 to 90 µmol/L with prolonged exposure ⁴¹ . Although most studies could not show nephrotoxic effects after sevoflurane anesthesia ⁴⁴ , some controversial reports ⁴⁵ of mild renal dysfunction after the use of sevoflurane resulted in a recommendation by the US Food and Drug Administration for caution in the use of sevoflurane in patients with coexisting renal disease. Interestingly, the majority of data report no differences in pharmacokinetics between patients with and those without kidney diseases ^{46, 47} . Percutaneous losses account for less than 1% of the total uptake of sevoflurane ⁴⁸ .

A decrease in ventilation leading to apnea at concentrations of between 1.5 and 2.0 MAC can be observed. The ventilatory depression with sevoflurane is the result of a combination of central depression of medullary respiratory neurons ⁴⁹ and depression of diaphragmatic function ⁵⁰ and contractility ⁵¹ .

Sevoflurane provides bronchodilation and attenuates bronchial smooth muscle constriction by histamine or acetylcholine and can be safely used in patients with asthma ²¹ . Hypoxic pulmonary vasoconstriction is inhibited by sevoflurane in a dose-dependent manner and is not mediated by cyclo-oxygenase ^{21– 23} .

Sevoflurane decreases blood pressure in a dose-dependent manner by decreasing total peripheral resistance. At clinically relevant concentrations, cardiac output is usually preserved ^{21– 23} . Heart rate remains unchanged or even decreases. Coronary blood flow remains preserved and regional blood flow to other vascular beds appears to be maintained at least when systemic hemodynamics are preserved. For sevoflurane (unlike for desflurane), no sympathetic nervous system activation is observed ^{21– 23} . Although sevoflurane has been reported to prolong the QT and the QTc interval ⁵² , it has no effect on the normal cardiac conduction pathways and therefore is considered a safe agent that can also be used in cardiac electrophysiological procedures ²⁵ .

Sevoflurane is a cerebral vasodilator. In neurosurgical patients, sevoflurane decreased middle cerebral artery flow velocity and caused no epileptiform electroencephalogram activity and no increase of intracranial pressure ⁵³ . Cerebral autoregulation is maintained at low concentrations of sevoflurane ⁵⁴ , but higher doses seem to decrease autoregulatory capacity ⁵⁵ .

There seems to be no significant difference in sevoflurane pharmacokinetics between children and adults ²⁴ . Because of its pleasant odor, lack of airway irritation, and maintenance of stable hemodynamics, sevoflurane is the agent of choice for mask induction. In general, complications upon emergence are infrequent, although some studies mention a significantly higher incidence of excitement/agitation with sevoflurane ^{69, 70} . However, this observation has been linked to the fact that the prompt recovery from anesthesia with sevoflurane also facilitates earlier awareness of postoperative pain ^{69, 71} . This causal relationship was confirmed in a number of studies demonstrating that adequate pain treatment was associated with significantly fewer episodes of emergence agitation ^{72, 73} .

Ambulatory surgery has increased rapidly in recent years and this has put an emphasis on the use of short-acting drugs in anesthetic practice, allowing fast recovery and early mobilization. Differences in early recovery between sevoflurane, desflurane, and propofol have been reported to be small but in favor of the inhaled anesthetics ⁷⁴ , although the clinical implications of these small differences are debatable. Postoperative nausea and vomiting are higher with volatile anesthetics than with propofol, but adequate anti-emetic prophylaxis can prevent or blunt this side effect.

The prevalence of obesity is increasing dramatically, not only in industrialized countries but also in developing ones. As a consequence, we encounter a growing number of morbidly obese patients who need different types of surgery. Obese patients are traditionally reported to have slower emergence from anesthesia because of a delayed release of volatile anesthetics from the excess fat tissue. However, comparable recovery times have been reported in obese and non-obese subjects after anesthetic procedures lasting 2 to 4 hours ⁷⁵ .

The new inhalation drugs have a much lower lipid solubility compared with the older volatile anesthetic agents, resulting in a more rapid and consistent recovery profile ⁷⁶ . For sevoflurane, no significant differences in F _A/F _I ratio have been observed, but the wash-out curve—that is, the alveolar-to-expiratory fraction (F _A/F _AO ratio)—was reported to be slower in obese patients compared with non-obese patients. However, 5 minutes after sevoflurane discontinuation, no differences in wash-out were observed between obese and non-obese patients ⁷⁷ . Several studies have compared kinetic profiles of sevoflurane and desflurane. Some studies observed more rapid emergence from anesthesia with desflurane but this was not confirmed in other studies (reviewed in 78). Finally, an advantage of sevoflurane in this setting is that it allows progressive induction of anesthesia via face mask ⁷⁹ .

The finding in the late 1990s that sevoflurane was capable of limiting the extent of myocardial infarction after myocardial ischemia triggered a new research direction investigating potential cardioprotective effects of volatile anesthetic agents. Experimental studies have clearly indicated that volatile anesthetic agents are capable of protecting the myocardium against the consequences of ischemia-reperfusion injury by decreasing the extent of myocardial damage, decreasing the extent of reperfusion injury, and better preserving myocardial function. Subsequent research was directed toward unraveling the underlying mechanisms and intracellular pathways of these cardioprotective effects ^{80– 85} .

Although the experimental evidence of cardioprotection with volatile anesthetic agents was quite straightforward, the implications for clinical practice remain a point of debate. The potential cardioprotective effects related to the use of volatile anesthetics were first explored in the setting of cardiac surgery. In coronary artery surgery patients, the results of preconditioning protocols were conflicting: some authors demonstrated a protective effect whereas others failed to observe such an effect. Later, it became clear that this might be attributed to the preconditioning protocol used. It also seems that the administration of the volatile anesthetic agent throughout the entire procedure results in a more pronounced protective effect than when administered intermittently. It is beyond the scope of this review to discuss these studies in detail. The interested reader is referred to a number of reviews on the topic ^{86– 95} .

For non-cardiac surgery, the potential clinical implication of the cardioprotective properties of volatile anesthetics is even more debatable. One small study in vascular surgery patients observed a lower incidence of cardiac complications in patients treated with sevoflurane compared with those anesthetized with propofol ⁹⁶ . Others, however, observed no difference in the extent of myocardial damage when comparing a volatile anesthetic regimen with a total intravenous regimen ^{97, 98} . This clearly indicates that only in the presence of myocardial ischemia/reperfusion injury can a potential beneficial effect of volatile anesthetics be expected ⁹⁹ . Interestingly, in the study by Lurati Buse and colleagues ⁹⁸ , in which 385 patients were randomly assigned to receive anesthesia with either sevoflurane or propofol, the incidences of perioperative myocardial ischemia were comparable (40.8% in the sevoflurane group and 40.3% in the propofol group). Within 12 months, 14 patients had a major cardiac event in the sevoflurane-treated group (7.6%) and 17 in the propofol-treated group (8.5%). However, given that a potential cardioprotective effect of volatile anesthetic agents relates to a modulation of the extent of myocardial ischemia/reperfusion injury, the analysis of the major cardiac events needs to be focused on the occurrence of these events in the subgroup of patients who had perioperative myocardial ischemia. To further clarify this issue, the authors performed an additional analysis of their data. They found that the incidence of major cardiac complications in patients with evidence of perioperative myocardial ischemia was similar in both groups: 8 out of 67 patients (11.9%) in the sevoflurane group and 9 out of 72 patients (12.9%) in the propofol group. The remaining 6 and 8 patients with postoperative major cardiac complications had not shown any evidence of perioperative myocardial ischemia (Seeberger M, unpublished observations).

Clinical studies on the protective effects of sevoflurane on other organ systems are scarce and limited to a small number of patients. Three studies from the same group suggest protective effects after liver ^{100, 101} and lung ¹⁰² ischemia with sevoflurane, but the potential implications on long-term outcome remain to be established.