Sevoflurane is a nonflammable liquid anesthetic agent administered by vaporization. It is a fluorinated derivative of methyl isopropyl ether.
Sevoflurane is identified chemically as fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether and has a molecular weight of 200.05.
Sevoflurane is a clear, colorless, liquid. Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform and petroleum benzene, and it is slightly soluble in water.
Sevoflurane has the following physical and chemical properties:
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Sevoflurane is nonflammable and non-explosive as defined by the requirements of International Electrotechnical Commission 601-2-13.
Sevoflurane is stable when stored under normal room lighting conditions. No discernible degradation of sevoflurane occurs in the presence of strong acids or heat. Sevoflurane is not corrosive to stainless steel, brass, aluminum, nickel-plated brass, chrome-plated brass or copper beryllium alloy.
Chemical degradation can occur upon exposure of inhaled anesthetics to carbon dioxide (CO2
) absorbent within the anesthesia machine. When used as directed with fresh absorbents, degradation of sevoflurane is minimal and degradants are undetectable or nontoxic. Sevoflurane degradation and subsequent degradant formation are enhanced by increasing absorbent temperature, desiccated CO2
absorbent (especially potassium hydroxide-containing), increased sevoflurane concentration and decreased fresh gas flow. Sevoflurane can undergo alkaline degradation by 2 pathways. The 1st results from the loss of hydrogen fluoride with the formation of pentafluoroisopropanyl fluoromethyl ether (PIFE or more commonly known as compound A). The 2nd pathway for degradation of sevoflurane occurs only in the presence of desiccated CO2
absorbents and leads to the dissociation of sevoflurane into hexafluoroisopropanol (HFIP) and formaldehyde. HFIP is inactive, nongenotoxic, rapidly glucuronidated, cleared and has toxicity comparable to sevoflurane. Formaldehyde is present during normal metabolic processes. Upon exposure to a highly desiccated absorbent, formaldehyde can further degrade into methanol and formate. Formate can contribute to the formation of carbon monoxide, in the presence of high temperature. Methanol can react with compound A to form the methoxy addition product compound B. compound B can undergo further HF elimination to form Compounds C, D and E. With highly desiccated absorbents, especially those containing potassium hydroxide, the formation of formaldehyde, methanol, carbon monoxide, Compound A and perhaps some of its degradants, Compounds B, C and D may occur.
Lewis Acid Degradation:
At least 300 ppm of water is added as a Lewis acid inhibitor. No other additives or chemical stabilizers are utilized.
Pharmacology: Pharmacodynamics: In a variety of animal species including man, sevoflurane has been demonstrated to be a fast-acting, non-irritating agent. Administration has been associated with a smooth, rapid loss of consciousness during inhalational induction and a rapid recovery following discontinuation of anesthesia.
Induction is accomplished, with a minimum of excitement or signs of upper respiratory irritation, no evidence of excessive secretions within the tracheobronchial tree and no central nervous system (CNS) stimulation. In pediatric studies in which mask induction was performed, the incidence of coughing was statistically significantly lower with sevoflurane than with halothane.
Like other potent inhalational anesthetics, sevoflurane depresses respiratory function and blood pressure in a dose-related manner.
In both dogs and humans, the epinephrine-induced arrhythmogenic threshold for sevoflurane was comparable to that of isoflurane and higher than that of halothane. Studies in dogs have demonstrated sevoflurane does not reduce collateral myocardial perfusion. In clinical studies, the incidence of myocardial ischemia and myocardial infarction in patients at risk for myocardial ischemia was comparable between sevoflurane and isoflurane.
Animal studies have shown regional blood flow (eg, hepatic, renal, cerebral circulations) is well-maintained with sevoflurane. In both animal studies (dogs, rabbits) and clinical studies, changes in neurohemodynamics (intracranial pressure, cerebral blood flow/blood flow velocity, cerebral metabolic rate for oxygen and cerebral perfusion pressure) were comparable between sevoflurane and isoflurane. Sevoflurane has minimal effect on intracranial pressure (ICP) and preserves CO2 responsiveness.
Sevoflurane does not affect renal concentrating ability, even after prolonged anesthetic exposure, up to approximately 9 hrs.
Minimum Alveolar Concentration (MAC): The MAC is the concentration at which 50% of the population tested does not move in response to a single stimulus of skin incision. For MAC equivalents of sevoflurane for various age groups, (see Dosage & Administration).
The MAC of sevoflurane in oxygen was determined to be 2.05% for an adult 40 years of age. As with other halogenated agents, MAC decreases with age and with the addition of nitrous oxide.
Clinical Studies: Efficacy: Numerous clinical studies have been conducted with sevoflurane as the anesthetic agent for pediatric and adult patients. The results have shown sevoflurane provides smooth, rapid induction of, as well as rapid emergence from, anesthesia.
Sevoflurane was associated with faster times to induction and to such recovery events as emergence, response to command and orientation compared to reference drugs.
Adult Anesthesia: Mask Induction: In adult studies in which mask induction was performed, sevoflurane was demonstrated to provide smooth and rapid induction of anesthesia.
Maintenance: In 3 outpatient and 25 inpatient studies involving 3591 adult patients (2022 sevoflurane, 1196 isoflurane, 111 enflurane, 262 propofol) sevoflurane was demonstrated to be an effective agent for the maintenance of anesthesia.
Sevoflurane was demonstrated to be an appropriate agent for use in neurosurgery, Cesarean section, patients undergoing coronary artery bypass surgery (CABG) and noncardiac patients at risk for myocardial ischemia.
Pediatric Anesthesia: In 2 outpatient and 3 inpatient studies involving 1498 pediatric patients (837 sevoflurane, 661 halothane), sevoflurane was demonstrated to be an effective agent for the induction and maintenance of anesthesia.
Mask Induction: In pediatric studies in which mask induction was performed, the induction time was statistically significantly shorter and the incidence of coughing was statistically significantly lower with sevoflurane than with halothane.
Safety: Clinical studies were conducted in a wide variety of patient populations (children, adults, elderly, renally and hepatically impaired, obese, patients undergoing cardiac bypass surgery, patients treated with aminoglycosides or metabolic inducers, patients exposed to repeat surgeries, patients undergoing surgeries ≥6 hrs in duration). The results of evaluations of laboratory parameters (eg, SGPT, SGOT, alkaline phosphatase, total bilirubin, serum creatinine, BUN) as well as investigator-reported incidence of adverse events relating to hepatic and renal function, demonstrated sevoflurane did not have a clinically significant effect on liver or kidney function, nor did it exacerbate preexisting renal or hepatic impairment within these study populations (see Precautions and Adverse Reactions). These studies also demonstrated there were no statistically significant differences between sevoflurane and reference agents in the proportions of patients showing changes in any clinical chemistry parameter.
The impact on renal function was comparable among sevoflurane and the reference drugs, between types of anesthesia circuits, among flow rates and between patients with or without inorganic fluoride concentrations ≥50 μm.
The incidence of renal dysfunction was <1% for both sevoflurane (0.17%) and reference drugs (0.22%; isoflurane, halothane, enflurane, propofol) in comparative studies. This overall incidence is consistent with that of a general surgical population. In all cases, an alternate cause or reasonable explanation existed for the renal dysfunction.
Hepatically Impaired: During clinical development, sevoflurane was effective and well tolerated when used as the primary agent for the maintenance of anesthesia in patients with impaired hepatic function, Child-Pugh class A and B, sevoflurane did not exacerbate pre-existing hepatic impairment.
For hepatic adverse events seen in post-marketing experience see Precautions-Hepatic and Adverse Reactions.
Renally Impaired: Sevoflurane was evaluated in renally impaired patients with baseline serum creatinine ≥1.5 mg/dL (130 μmole/L). Based on the incidence and magnitude of changes in serum creatinine concentrations, sevoflurane did not further deteriorate renal function.
Pharmacokinetics: Solubility: The low solubility of sevoflurane in blood would suggest alveolar concentrations should rapidly increase upon induction and rapidly decrease upon cessation of the inhaled agent. This was confirmed in a clinical study where inspired and end-tidal concentrations (FI and FA) were measured. The FA/FI, (wash-in) value at 30 min for sevoflurane was 0.85. The FA/FAO (washout) value at 5 min was 0.15.
Distribution: The effects of sevoflurane on the displacement of drugs from serum and tissue proteins have not been investigated. Other fluorinated volatile anesthetics have been shown to displace drugs from serum and tissue proteins in vitro. The clinical significance of this is unknown. Clinical studies have shown no untoward effects when sevoflurane is administered to patients taking drugs that are highly bound and have a small volume of distribution (eg, phenytoin).
Metabolism: The rapid pulmonary elimination of sevoflurane minimizes the amount of anesthetic available for metabolism. In humans <5% sevoflurane absorbed is metabolized via cytochrome P450 2E1 isoform to hexafluorisopropanol (HFIP), with release of inorganic fluoride and CO2 (or a 1 carbon fragment). Once formed HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane have been identified. It is the only fluorinated volatile anesthetic which is not metabolized to trifluoroacetic acid.
Fluoride Ion: Fluoride ion concentrations are influenced by the duration of anesthesia, the concentration of sevoflurane administered and the composition of the anesthetic gas mixture.
The defluorination of sevoflurane is not inducible by barbiturates.
Approximately 7% of adults evaluated for inorganic fluoride concentrations in the Abbott Clinical Program experienced concentrations >50 μm; no clinically significant effect on renal function was observed in any of these individuals (see Inducers of CYP2E1 under Interactions).
Toxicology: Preclinical Safety Data: Sevoflurane has a low order of acute toxicity in rats, mice, rabbits, dogs and monkeys. Anesthesia induction was smooth and rapid, with no struggling, signs of gasping or other undesirable reactions. Deaths from exposure to lethal concentrations were due to respiratory arrest. Exposure was not associated with any specific organ toxicity or developmental toxicity in laboratory animals.
Fischer 344 rats were anesthetized within 2-3 min after start of exposure to sevoflurane (1.4%) for up to 10 hrs. There were no functional or morphologic defects following administration of sevoflurane.
In a segment I reproduction study, sevoflurane had no significant effects on male or female reproductive capabilities at exposure concentrations of up to 1 MAC (2.2%). Segment II and III studies in rats indicate sevoflurane is not a selective developmental toxicant.
Compound A: In Wistar rats, the LC50 of Compound A was 1,050-1,090 ppm in animals exposed for 1 hr and 400-420 ppm in animals exposed for 3 hrs (median lethal concentrations were approximately 1070 and 330-490 ppm, respectively). In rats exposed to 30, 60 or 120 ppm of Compound A in an 8-week chronic toxicity study (24 exposures, 3 hrs/exposure), no apparent evidence of toxicity was observed other than loss of body weight in females on the last study day.
Sprague-Dawley rats were administered with Compound A via nose-only inhalation exposure in an open system [25, 50, 100 or 200 ppm (0.0025-0.02%) of Compound A]. Control groups were exposed to air. The threshold, at which reversible alterations in urinary and clinical parameters indicative of renal changes (concentration-dependent increases in BUN, creatinine, glucose, protein/creatinine ratios and N-acetyl-glucosamidase/creatinine ratios) were observed, was 114 ppm of Compound A. Histological lesions were all reversible.
Since the uptake of inhalational agents in small rodents is substantially higher than in humans, higher levels of drug, Compound A (degradant of sevoflurane) or 2-bromo-2-chloro-1,1-difluoro ethylene (BCDFE) (degradant/metabolite of halothane) would be expected in rodents. Also the activity of the key enzyme (β-lyase) involved in haloalkene nephrotoxicity is 10-fold greater in the rat than it is in humans.
Compound A concentrations are reported to increase with increasing absorber temperature, increasing sevoflurane concentrations and with decreasing fresh gas flow rates. It has been reported that the concentration of Compound A increases significantly with prolonged dehydration of Baralyme. In the clinical situation, the highest concentration of compound A in the anesthesia circuit with soda lime as the CO2 absorbent was 15 ppm in pediatrics and 32 ppm in adults. However, concentrations to 61 ppm have been observed in patients attached to systems with Baralyme as the CO2 absorbent. The level of Compound A at which toxicity occurs in humans is not known. Although exposure to sevoflurane in low flow systems is limited, there has been no evidence of renal dysfunction attributable to Compound A.
Compound B: In the clinical situation, the concentration of Compound B detected in the anesthesia circuit did not exceed 1.5 ppm. Inhalation exposure to Compound B at concentrations of up to 2,400 ppm (0.24%) for 3 hrs resulted in no adverse effects on renal parameters or tissue histology in Wistar rats.
Carcinogenesis: Studies on carcinogenesis have not been performed. No mutagenic effect was noted in the Ames test and no chromosomal aberrations were induced in cultured mammalian cells.
Induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.
Premedication: Premedication should be selected according to the need of the individual patient and at the discretion of the anesthesiologist.
The concentration of sevoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane.
Dosage should be individualized and titrated to the desired effect according to the patient's age and clinical status. A short-acting barbiturate or other IV induction agent may be administered followed by inhalation of sevoflurane. Induction with sevoflurane may be achieved in oxygen or in combination with oxygen-nitrous oxide mixtures. For induction of anesthesia, inspired concentrations of up to 8% sevoflurane usually produces surgical anesthesia in <2 min in both adults and children.
Maintenance: Surgical levels of anesthesia may be sustained with concentrations of 0.5-3% sevoflurane with or without the concomitant use of nitrous oxide (see Nitrous Oxide under Interactions). (See Table 3.)
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Emergence: Emergence times are generally short following sevoflurane anesthesia. Therefore, patients may require postoperative pain relief earlier.
Minimum alveolar concentration decreases with increasing age. The average concentration of sevoflurane to achieve MAC in an 80 years of age is approximately 50% of that required in a 20 years of age.
In the event of apparent overdosage, the following action should be taken: discontinue administration of sevoflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen and maintain adequate cardiovascular function.
Sevoflurane should not be used in patients with known or suspected genetic susceptibility to malignant hyperthermia.
Sevoflurane should not be used in patients with known or suspected sensitivity to sevoflurane or to other halogenated inhalational anesthetics (e.g. history of hepatotoxicity, usually including elevated liver enzymes, fever, leukocytosis and/or eosinophilia temporally related to anesthesia with one of these agents).
Sevoflurane should be administered only by persons trained in the administration of general anesthesia. Facilities for maintenance of a patent airway, artificial ventilation and oxygen enrichment and circulatory resuscitation must be immediately available.
The concentration of sevoflurane being delivered from a vaporizer must be known exactly. As volatile anesthetics differ in their physical properties, only vaporizers specifically calibrated for sevoflurane should be used. The administration of general anesthesia must be individualized based on the patient's response. Hypotension and respiratory depression increase as anesthesia is deepened.
Isolated reports of QT prolongation, very rarely associated with Torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering sevoflurane to susceptible patients.
Isolated cases of ventricular arrhythmia were reported in pediatric patients with Pompe's disease.
Caution should be exercised when administering general anesthesia, including sevoflurane to patients with mitochondrial disorders.
Hepatic: Very rare case of mild, moderate and severe postoperative hepatic dysfunction or hepatitis with or without jaundice have been reported in post-marketing experiences.
Clinical judgment should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction (see Adverse Reactions).
It has been reported that previous exposure to halogenated hydrocarbon anesthetics, especially if the interval is <3 months, may increase the potential to hepatic injury.
Malignant Hyperthermia: In susceptible individuals, potent inhalation anesthetic agents, including sevoflurane, may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. The clinical syndrome is signaled by hypercapnia and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia, acute hypoxia, hypercapnia and hypovolemia.
In clinical trials, 1 case of malignant hyperthermia was reported.
In addition, there have been post-marketing reports of malignant hyperthermia. Some of these have been fatal.
Treatment of malignant hyperthermia includes discontinuation of triggering agents (eg, sevoflurane), administration of IV dantrolene sodium and application of supportive therapy (consult prescribing information of IV dantrolene sodium for additional information on patient management), and application of support therapy. Such therapy includes vigorous efforts to restore body temperature to normal, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base abnormalities. Renal failure may appear later and urine flow should be monitored and sustained if possible.
Preoperative Hyperkalemia: Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
General: During maintenance of anesthesia, increasing the concentration of sevoflurane produces dose-dependent decreases in blood pressure. Excessive decrease in blood pressure may be related to depth of anesthesia and in such instances may be corrected by decreasing the inspired concentration of sevoflurane.
As with all anesthetics, maintenance of hemodynamic stability is important to the avoidance of myocardial ischemia in patients with coronary artery disease.
The recovery from general anesthesia should be assessed carefully before patients are discharged from the post-anesthesia care unit.
Although recovery of consciousness following sevoflurane administration generally occurs within minutes, the impact on intellectual function for 2 or 3 days following anesthesia has not been studied. As with other anesthetics, small changes in moods may persist for several days following administration (see Effects on the Ability to Drive and Use Machines).
Replacement of Desiccated CO2 Absorbents: Rare cases of extreme heat smoke; and/or spontaneous fire in the anesthesia machine have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent, specifically those containing potassium hydroxide. An unusually delayed rise or unexpected decline of inspired sevoflurane concentration compared to the vaporizer setting may be associated with excessive heating of the CO2 absorbent canister.
An exothermic reaction, enhanced sevoflurane degradation and production of degradation products (see Description) can occur when the CO2 absorbent becomes desiccated such as, after an extended period of dry gas flow through the CO2 absorbent canisters. Sevoflurane degradants (methanol, formaldehyde, carbon monoxide and Compounds A, B, C and D) were observed in the respiratory circuit of an experimental anesthesia machine using desiccated CO2 absorbents and maximum sevoflurane concentrations (8%) for extended periods of time (≥2 hrs). Concentrations of formaldehyde observed at the anesthesia respiratory circuit (using sodium hydroxide containing absorbents) were consistent with levels known to cause mild respiratory irritation. The clinical relevance of the degradants observed under this extreme experimental model is unknown.
When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced before administration of sevoflurane. The color indicator of most CO2 absorbents does not necessarily change as a result of desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. Carbon dioxide absorbents should be replaced routinely, regardless of the state of the color indicator.
Renal Impairment: Because of the small number of patients with renal insufficiency (baseline serum creatinine >1.5 mg/dL) studied, the safety of sevoflurane administration in this group has not yet been fully established. Therefore, sevoflurane should be used with caution in patients with renal insufficiency.
Neurosurgery: In patients at risk for elevations of ICP, sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers eg, hyperventilation.
Seizures: Rare cases of seizures were reported in association with sevoflurane (see Pediatric Use as follows and Adverse Reactions).
Drug Abuse and Dependence: None known.
Effects on Ability to Drive and Use Machines: Patients should be advised that performance of activities requiring mental alertness, such as, operating a motor vehicle or hazardous machinery, may be impaired for some time after general anesthesia.
Use in pregnancy & lactation: Pregnancy Category B: Reproduction studies in rats and rabbits at doses up to 1 MAC have revealed no evidence of impaired fertility or harm to the fetus due to sevoflurane. There are no adequate and well-controlled studies in pregnant women; therefore, sevoflurane should be used during pregnancy only if clearly needed.
Labor and Delivery: In a clinical trial, the safety of sevoflurane was demonstrated for mothers and infants when used for anesthesia during cesarean section. The safety of sevoflurane in labor and vaginal delivery has not been demonstrated.
Sevoflurane, like, other inhalational agents, has relaxant effect on the uterus with the potential risk of uterine bleeding. Clinical judgment should be observed when using sevoflurane during obstetric anesthesia.
It is not known whether sevoflurane or its metabolites is excreted in human milk. Due to the absence of documented experience, women should be advised to skip breastfeeding for 48 hrs after administration of sevoflurane and discard milk produce during this period.
As with all potent inhaled anesthetics, sevoflurane may cause dose-dependent cardiorespiratory depression. Most adverse events are mild or moderate in severity and transient in duration. Nausea and vomiting have been observed in the postoperative period, common sequelae of surgery and general anesthesia, which may be due to inhalational anesthetic, other agents administered intraoperatively or postoperatively, and to the patient's response to the surgical procedure.
As with potent inhaled anesthetics, sevoflurane may cause dose-dependent cardiorespiratory depression. Most adverse events are mild or moderate in severity and transient in duration. Nausea and vomiting have been observed in the postoperative period, common sequelae of surgery and general anesthesia, which may due to inhalational anesthetic, other agents administered intra-operatively or postoperatively, and to the patient's response to the surgical procedure. The most commonly reported adverse reactions were as follows: Adult Patients:
Hypotension, nausea and vomiting.
Bradycardia, hypotension and nausea.
Agitation, cough, vomiting and nausea.
All events, at least possibly related to sevoflurane from clinical trials are listed in Table as follows by MedDRA System Organ Class, Preferred Term and frequencies. The following frequency grouping are used: very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1,000 and <1/100); rare (≥1/10,000 and <1/1,000); very rare (<1/10,000) including isolated reports. The type, severity and frequency of adverse events in sevoflurane patients were comparable to adverse events in reference-drug patients. (See Table 4.)
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ADR Post-Marketing Experience:
Adverse events have been spontaneously reported during post approval use of sevoflurane. These events are reported voluntarily from population of an unknown rate of exposure. Therefore, it is not possible to estimate the true incidence of adverse events or establish a causal relationship to Sevoflurane exposure. (See Table 5.)
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Sevoflurane has been shown to be safe and effective when administered concurrently with a wide variety of agents commonly encountered in surgical such as, CNS agents, autonomic drugs, skeletal muscle relaxants, anti-infective agents including aminoglycosides, hormones and synthetic substitutes, blood derivatives and cardiovascular drugs, including epinephrine.
Barbiturates: Sevoflurane administration is compatible with barbiturates as commonly used in surgical practice.
Benzodiazepines and Opioids: Benzodiazepines and opioids are expected to decrease the MAC of sevoflurane in the same manner as with other inhalational anesthetics. Sevoflurane administration is compatible with benzodiazepines and opioids as commonly used in surgical practice.
Inducers of CYP2E1: Medicinal products and compounds that increase the activity of CYP450 isoenzyme CYP2E1 such as isoniazid and alcohol, may increase the metabolism of sevoflurane and lead to significant increases in plasma fluoride concentrations (see Pharmacology: Pharmacokinetics under Actions).
Nitrous Oxide: As with other halogenated volatile anesthetics, the MAC of sevoflurane is decreased when administered in combination with nitrous oxide. The MAC equivalent is reduced approximately 50% in adult and approximately 25% in pediatric patients (see Dosage & Administration).
Neuromuscular Blocking Agents: As with other inhalational anesthetic agents, sevoflurane affects both the intensity and duration of neuromuscular blockade by nondepolarizing muscle relaxants. When used to supplement alfentanil-N2O anesthesia, sevoflurane potentiates neuromuscular block induced with pancuronium, vecuronium or atracurium. The dosage adjustments for these muscle relaxants when administered with sevoflurane are similar to those required with isoflurane. The effect of sevoflurane on succinylcholine and the duration of depolarizing neuromuscular blockade has not been studied.
Dosage reduction of neuromuscular blocking agents during induction of anesthesia may result in delayed onset of conditions suitable for endotracheal intubation or inadequate muscle relaxation because potentiation of neuromuscular blocking agents is observed a few minutes after the beginning of sevoflurane administration.
Among nondepolarizing agents, vecuronium, pancuronium and atracurium interactions have been studied. In the absence of specific guidelines: (1) for endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants; and, (2) during maintenance of anesthesia, the dose of nondepolarizing muscle relaxants is likely to be reduced compared to that during N2O/opioid anesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation.
Store at temperature not exceeding 30°C.
N01AB08 - sevoflurane ; Belongs to the class of halogenated hydrocarbons. Used as general anesthetics.
Inhalation vapour liqd (wet formulation, clear, colorless) 250 mL.