Sevoflurane is a fluorinated derivative of methyl isopropyl ether. The chemical name is fluoromethyl 2, 2, 2-trifluoro-1-(trifluoromethyl) ethyl ether and its structural formula is as follows:

F3C

H C OCH2F

F3C

Description

Sevoflurane is a nonflammable and non-explosive liquid administered by vaporization. It is a clear, colorless, nonpungent liquid. At least 300ppm of water is present to provide protection from environmental Lewis acids. No other additives or chemical stabilizers are utilized. It is miscible with ethanol, ether, chloroform and petroleum benzene and is slightly soluble in water. Sevoflurane has the following physical and chemical properties:

Mean Component/Gas Partition Coefficients at 25oC for polymers commonly used in medical applications:

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, aluminium, nickel-plated brass, chrome-plated brass, or copper beryllium alloy. Chemical degradation can occur upon exposure of inhaled anaesthetics to CO2 absorbent within the anaesthesia machine. When used as directed with fresh absorbents, degradation of sevoflurane is minimal, and degradants are undetectable or non-toxic. Sevoflurane degradation and subsequent degradant formation are enhanced by increasing absorbent temperature, desiccated CO2 absorbent (especially potassium hydroxide-containing, e.g. Baralyme), increased sevoflurane concentration and decreased fresh gas flow. Sevoflurane can undergo alkaline degradation by two pathways. The first results from the loss of hydrogen fluoride with the formation of pentafluoroisopropanyl fluoromethyl ether (PIFE or more commonly known as Compound A). The second 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, non-genotoxic, rapidly glucoronidated, 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 (e.g. Baralyme ), the formation of formaldehyde, methanol, carbon monoxide, Compound A and perhaps some of it's degradants, Compounds B, C and D may occur.

Pharmacology

Pharmacodynamics

Sevoflurane has been demonstrated to be a fast-acting, non-irritating anaesthetic agent in a variety of animal species and in humans. Administration has been associated with a smooth, rapid loss of consciousness during inhalation induction and a rapid recovery following discontinuation of anaesthesia. Induction is accomplished, with a minimum of excitement or of signs of upper respiratory irritation, no evidence of excessive secretions within the tracheobronchial tree and no central nervous system stimulation. In paediatric studies in which mask induction was performed, the incidence of coughing was statistically significantly lower with sevoflurane than with halothane. The times for induction and recovery were also reduced in these patients. Like other potent inhalational anaesthetics, sevoflurane depresses respiratory function and blood pressure in a dose-related manner. Sevoflurane has been demonstrated to be an appropriate agent for use in neurosurgery, caesarean section, coronary artery bypass surgery and in non-cardiac patients at risk for myocardial ischaemia. The adrenaline-induced arrhythmogenic threshold for sevoflurane is comparable to that of isoflurane and higher than that of halothane. Studies in dogs have demonstrated that sevoflurane does not reduce collateral myocardial perfusion. In clinical studies, the incidence of myocardial ischaemia and myocardial infarction in patients at risk for myocardial ischaemia was comparable between sevoflurane and isoflurane.

Animal studies have shown that regional blood flow (e.g., 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 intra-cranial pressure and preserves CO2 responsiveness. Sevoflurane does not affect renal concentrating ability, even after prolonged anaesthetic exposure of up to approximately 9 hours. For MAC equivalents for sevoflurane for various age groups, see Dosage and Administration section. As with other halogenated agents, minimum alveolar concentration (MAC) decreases with age and with the addition of nitrous oxide.

Pharmacokinetics

The low solubility of sevoflurane in blood would suggest that 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 (washin) value at 30 minutes for sevoflurane was 0.85. The FA/FAO (washout) value at 5 minutes was 0.15.

The effects of sevoflurane on the displacement of medicines from serum and tissue proteins have not been investigated. Other fluorinated volatile anaesthetics have been shown to displace medicines 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 medicines that are highly bound and have a small volume of distribution (e.g. phenytoin).

The rapid pulmonary elimination of sevoflurane minimizes the amount of anaesthetic available for metabolism. In humans <5% of sevoflurane absorbed is metabolized to hexafluoroisopropanol (HFIP), with release of inorganic fluoride and carbon dioxide (or a one carbon fragment). Once formed HFIP is rapidly conjugated with glucuronic acid and eliminated. No other metabolic pathways for sevoflurane have been identified. It is the only fluorinated volatile anaesthetic that is not metabolized to trifluoroacetic acid.

Fluoride ion concentrations are influenced by the duration of anaesthesia, the concentration of sevoflurane administered, and the composition of the anaesthetic gas mixture. Inorganic fluoride concentrations peak within two hours of the end of sevoflurane anaesthesia and return to baseline concentrations within 48 hours post anaesthesia. Approximately 7% of adults evaluated for inorganic fluoride concentrations in Abbott clinical studies experienced concentrations greater than 50 M; no clinically significant effect on renal function was observed in any of these individuals (see Interactions With Other Medicines - Inducers of CYP2E1). The defluorination of sevoflurane is not inducible by barbiturates.

Contraindications

Sevoflurane should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents (e.g. history of hepatotoxicity, usually including elevated liver enzymes, fever, leukocytosis and/or eosinophilia temporally related to anaesthesia with one of these agents) or with known or suspected genetic susceptibility to malignant hyperthermia.

Precautions

Sevoflurane should be administered only by persons trained in the administration of general anaesthesia. Facilities for maintenance of a patent airway, artificial ventilation and oxygen enrichment and circulatory resuscitation must be immediately available. Since levels of anaesthesia may be altered easily and rapidly, only vaporizers specifically calibrated for sevoflurane should be used. Hypotension and respiratory depression increase as anaesthesia 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. During maintenance of anaesthesia, increasing the concentration of sevoflurane produces dose-dependent decreases in blood pressure. Excessive decrease in blood pressure may be related to depth of anaesthesia and in such instances may be corrected by decreasing the inspired concentration of sevoflurane. As with all anesthetics, maintenance of haemodynamic stability is important to the avoidance of myocardial ischaemia in patients with coronary artery disease. The recovery from general anaesthesia should be assessed carefully before patients are discharged from the post-anesthesia care unit.

Replacement of Desiccated CO2 Absorbents

Rare cases of extreme heat, smoke, and/or spontaneous fire in the anaesthesia machine have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent, specifically those containing potassium hydroxide (e.g. Baralyme). 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 Further Information) 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 anaesthesia machine using desiccated CO2 absorbents and maximum sevoflurane concentrations (8%) for extended periods of time (>2 hours). Concentrations of formaldehyde observed at the anaesthesia 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 colour indicator of most CO2 absorbents does not necessarily change as a result of desiccation. Therefore, the lack of significant colour change should not be taken as an assurance of adequate hydration. CO2 absorbents should be replaced routinely regardless of the state of the colour indicator.

Compound A

The LC50 of compound A in Wistar rats was 1050-1090ppm in animals exposed for 1 hour and 400-420ppm in animals exposed for 3 hours (median lethal concentrations were approximately 1070 and 330-490ppm, respectively). In rats exposed to 30, 60, or 120ppm of Compound A in a 8-week chronic toxicity study (24 exposures, 3 hours/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 Compound A via nose-only inhalation exposure in an open system (25, 50, 100 or 200ppm [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 114ppm 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 medicine, 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 (b-lyase) involved in haloalkene nephrotoxicity is ten-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 anaesthesia circuit with soda lime as the CO2 absorbent was 15 ppm in paediatrics 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 anaesthesia circuit did not exceed 1.5 ppm. Inhalation exposure to Compound B at concentrations of up to 2400 ppm (0.24%) for 3 hours resulted in no adverse effects on renal parameters or tissue histology in Wistar rats.

Malignant Hyperthermia

In susceptible individuals, potent inhalation anaesthetic 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 non-specific signs may also appear during light anaesthesia, acute hypoxia, hypercapnia and hypovolemia. In clinical trials, one case of malignant hyperthermia was reported. In addition, there have been post-marketing reports of malignant hyperthermia. Some of these reports have been fatal. Treatment of malignant hyperthermia includes discontinuation of triggering agents (e.g. sevoflurane), administration of intravenous dantrolene sodium (consult prescribing information for intravenous dantrolene sodium for additional information on patient

management), and application of supportive 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.

Hyperkalaemic Cardiac Arrest in Paediatric Patients

Use of inhaled anaesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in paediatric 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 creatine 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 hyperkalaemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.

Carcinogenicity /Mutagenicity

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.

Use in Pregnancy

Reproduction studies in rats and rabbits at doses up to 1 MAC have revealed no evidence of impaired fertility or harm to the foetus due to sevoflurane. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, sevoflurane should be used during pregnancy only if clearly needed. The safety of sevoflurane has been demonstrated in a clinical trial of anaesthesia for caesarean section. The safety of sevoflurane in labor and vaginal delivery has not been demonstrated. Sevoflurane, like other inhalational agents, has relaxant effects on the uterus with the potential risk for uterine bleeding. Clinical judgment should be observed when using sevoflurane during obstetric anaesthesia.

Use in Lactation

It is not known whether sevoflurane is excreted in human milk. Because many medicines are excreted in human milk, caution should be exercised when sevoflurane is administered to a nursing woman.

Paediatric Use

The use of sevoflurane has been associated with seizures. Many of these have occurred in children and young adults starting from 2 months of age, most of whom had no predisposing risk factors. Clinical judgment should be exercised when using sevoflurane in patients who may be at risk for seizures (see Adverse Effects).

Elderly

MAC decreases with increasing age. The average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old.

Renal Impairment

Because of the small number of patients with renal insufficiency (baseline serum creatinine greater than 1.5 mg/dL) studied, the safety of sevoflurane administration in this group has not been fully established. Therefore, sevoflurane should be used with caution in patients with renal insufficiency.

Hepatic Impairment

Very rare cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported from postmarketing 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 Effects). It has been reported that previous exposure to halogenated hydrocarbon anaesthetics, especially if the interval is less than 3 months, may increase the potential for hepatic injury.

Neurosurgery

In patients at risk for elevations of intracranial pressure (ICP), sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers such as hyperventilation.

Seizures

Rare cases of seizures have been reported in association with sevoflurane use (see Precautions - Paediatric Use and Adverse Effects).

Adverse Effects

Clinical Trials

As with all potent inhaled anesthetics, sevoflurane may cause dose-dependent cardio- respiratory 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 anaesthesia, which may be due to inhalational anaesthetic, other agents administered intra-operatively or post-operatively and to the patient's response to the surgical procedure. The most frequent adverse events (> 10%) considered to be probably related to sevoflurane administration overall were: nausea, vomiting, increased cough and hypotension. In adult patients the most frequent adverse events (> 10%) were: nausea, vomiting and hypotension. In elderly patients the most frequent adverse events (> 10%) were: hypotension, nausea and bradycardia. In pediatric patients, the most frequent adverse events (> 10%) were: vomiting, agitation, increased cough, and nausea. The type, severity and frequency of adverse events in sevoflurane patients were comparable to adverse events in reference medicine patients. All events, at least possibly related to sevoflurane from clinical trials, are displayed in the Table below by MedDRA System Organ Class, Preferred Term and frequency. The following frequency groupings 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.

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Summary of Most Frequent Adverse Drug Reactions in Sevoflurane Clinical Trials
System Organ Class	Frequency	Adverse Effects
Psychiatric disorders	Very Common	Agitation
Cardiac disorders	Common	Somnolence Dizziness Headache
Vascular disorders	Very Common Common Uncommon	Bradycardia Hypotension Tachycardia Hypertension Atrioventricular block complete
Respiratory, thoracic and mediastinal disorders	Very Common Common	Cough Respiratory disorder Laryngismus
Gastrointestinal disorders	Very Common Common	Nausea Vomiting Increased salivation
General disorders and administration site conditions	Common	Chills Pyrexia
Investigations	Common	Blood glucose elevation Liver function test abnormal White blood cell count elevation Fluoride increased
Injury, poisoning and procedural complications	Common	Hypothermia

In clinical studies administration of sevoflurane has not been associated with any clinically significant effect on liver or kidney function in a wide variety of patient populations including children, adults, elderly, renally impaired, hepatically impaired, obese, patients undergoing cardiac bypass surgery, patients treated with aminoglycerides or metabolic inducers, patients exposed to repeat surgeries, patients undergoing surgeries 6 hours in duration.

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Post Marketing Experience

Adverse events have been spontaneously reported during post-approval use of sevoflurane. These events are reported voluntarily from a 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.

Summary of Post-Marketing Adverse Drug Events
System Organ Class	Adverse Events
Immune system disorders	Anaphylactic reaction * * * Anaphylactoid reaction Hypersensitivity * * *
Nervous system disorders	Convulsion Dystonia
Cardiac disorders	Cardiac arrest #
Respiratory, thoracic and mediastinal disorders	Bronchospasm Dyspnoea * * * Wheezing * * *
Hepato-biliary disorders	Hepatitis Hepatic failure Hepatic necrosis
Skin and subcutaneous tissue disorders	Rash * * * Urticaria Pruritus Dermatitis contact * * * Swelling Face * * *
General disorders and administration site conditions	Hyperthermia malignant Chest discomfort * * *
* * * May be associated with hypersensitivity reactions, particularly in association with long-term occupational exposure to inhaled anaesthetic agents # There have been very rare postmarketing reports of cardiac arrest in the setting of sevoflurane use.

Seizure-like activity may occur on extremely rare occasions following sevoflurane administration. Reported events were of short duration and there was no evidence of any abnormality during emergence from anaesthesia or in the postoperative period

Interactions With Other Medicines

Sevoflurane has been shown to be safe and effective when administered concurrently with a wide variety of agents commonly encountered in surgical situations such as central nervous system agents, autonomic medicines, smooth muscle relaxants, anti- infective agents including aminoglycosides, hormones and synthetic substitutes, blood derivatives and cardiovascular medicines including epinephrine [1]. 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 cytochrome P450 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 of Fluoride Ion).

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.

Neuromuscular Blocking Agents

As with other inhalational anaesthetic agents, sevoflurane affects both the intensity and duration of neuromuscular blockade by non-depolarizing muscle relaxants. When used to supplement alfentanil-N2O anaesthesia, 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 suxamethonium chloride and the duration of depolarizing neuromuscular blockade has not been studied. Dosage reduction of neuromuscular blocking agents during induction of anaesthesia 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 non-depolarizing 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 non-depolarizing muscle relaxants, (2) during maintenance of anaesthesia, the dose of non-depolarizing muscle relaxants is likely to be reduced compared to that during N2O/opioid anaesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation.

Dosage and Administration

The concentration of sevoflurane being delivered from a vaporizer during anaesthesia should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane.

Premedication

Premedication should be selected according to the needs of the individual patient, and at the discretion of the anaesthetist.

Induction

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 intravenous 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 anaesthesia, inspired concentrations of up to 8%

sevoflurane usually produces surgical anaesthesia in less than two minutes in both adults and children.

Maintenance

Surgical levels of anaesthesia may be sustained with concentrations of 0.5 - 3% sevoflurane with or without the concomitant use of nitrous oxide (see table).

Elderly: As with other inhalation agents, lesser concentrations of sevoflurane are normally required to maintain anaesthesia.

Emergence

Emergence times are generally short following sevoflurane anaesthesia. Therefore, patients may require post-operative pain relief earlier.

Hepatic impairment

Sevoflurane is effective and well-tolerated when used as the primary agent for the maintenance of anaesthesia in patients with impaired hepatic function, Child-Pugh Class A and B. Sevoflurane did not exacerbate pre-existing hepatic impairment.

Renal impairment

Overdosage

In the event of 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.

Presentation and Storage Conditions

Sevoflurane should be stored at room temperature (Below 30degC). Sevoflurane has been demonstrated to be stable for the period defined by the expiration dating on the label. Sevoflurane is packaged in 100 mL * or 250 mL amber-coloured bottles.

Medicine Classification

Name and Address

New Zealand Date of Preparation

22 November 2012 Version 06 [i] International Medical Datasheet Update - Navarro R et al. Humans anaesthetised with sevoflurane or isoflurane have similar arrhythmic response to epinephrine. Anaesthesiology 1994 Mar; 80 (3): 545-9.

Physical / Chemical Property	Value
Boiling Point at 760 mm Hg	58.6degC
Specific Gravity at 20degC	1.520-1.525
Vapor pressure in mm Hg * *	157 mm Hg at 20degC 197 mm Hg at 25degC 317 mm Hg at 36degC
* *The equation for calculated vapor pressure in mm Hg: Log 10 P vap =A+B/T Where: A = 8.086; B = -1726.68; T = degC + 273.16degK (Kelvin)

Blood / Gas	0.63-0.69
Water / Gas	0.36
Olive Oil / Gas	47.2-53.9
Brain / Gas	1.15

Polymer	Mean Component/Gas Partition Coefficients at 25degC
Conductive rubber	14.0
Butyl rubber	7.7
Polyvinyl chloride	17.4
Polyethylene	1.3

MAC Values for Adults and Paediatric Patients According to Age
Age of Patient (Years)	Sevoflurane in Oxygen	Sevoflurane in 65% N 2 0/35% 0 2
0 - 1 months *	3.3%
1 - <6 months	3.0%
6 months - <3 years	2.8%	2.0% @
3 - 12	2.5%
25	2.6%	1.4%
40	2.1%	1.1%
60	1.7%	0.9%
80	1.4%	0.7%
* Neonates are full-term gestational age. MAC in premature infants has not been determined.
@ In 3 - <5 1 - <3 [1] year old paediatric patients, 60% N 2 0/40% 0 2 was used.

Sevorane TM

Name of the Medicine

Chemical Structure

F3C

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