Sevoflurane (Inhalation-Systemic)


VA CLASSIFICATION
Primary: CN201

Commonly used brand name(s): Sevorane; Ultane.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anesthetic (general)—

Indications

Accepted

Anesthesia, general—Sevoflurane is indicated for the induction and maintenance of general anesthesia in adult and pediatric patients during inpatient or outpatient surgery. Often, sevoflurane is used with other medications to induce or supplement anesthesia {01} {65}.

Unaccepted
Sevoflurane does not have analgesic activity at subanesthetic concentrations and is not recommended as an analgesic {02}.


Pharmacology/Pharmacokinetics

Note: Concentration-response relationships for inhalation anesthetics are described in terms of the minimum alveolar concentration (MAC), which is defined as the alveolar concentration that prevents movement in 50% of patients after surgical skin incision. The MAC decreases with pregnancy, hypothermia, hypotension, increasing age, and concurrent use of other central nervous system (CNS) depressants, including other inhalation anesthetics. Average MAC values for sevoflurane (vaporized in oxygen) are 3.3%, 3%, 2.6%, 1.7%, and 1.4% for neonates, and patients 1 to 6 months, 25 years, 60 years, and 80 years of age, respectively {01}. While MAC is commonly used to compare the concentration-response relationships for inhalation anesthetics, the AD 95 (the dose preventing 95% of patients from moving in response to skin incision) is more clinically relevant in dosing patients with inhalation anesthetics, if the inhalation anesthetic is used alone {03}. Often, inhalation anesthetics are used in combination with other agents to supplement anesthesia.


Physicochemical characteristics:

Chemical group—
    A halogenated hydrocarbon (methyl ethyl ether) anesthetic.
Molecular weight—
    200.06 {04}


Other characteristics
    MAC in oxygen for adults 40 years of age: 2.1% {01}.
    Blood-to-gas partition coefficient (37 °C [98.6 °F]): 0.63 to 0.69 {01}.
    Brain-to-gas partition coefficient (37 °C [98.6 °F]): 1.15 {01}.
    Oil-to-gas partition coefficient (37 °C [98.6 °F]): 47 to 54 {01}.

Mechanism of action/Effect:

The precise mechanism by which inhalation anesthetics produce loss of perception of sensations and unconsciousness is not known. Inhaled anesthetics act at many areas in the CNS. The Meyer-Overton theory suggests that the site of action of inhalation anesthetics may be the lipid matrix of neuronal membranes or other lipophilic sites. Anesthetics may cause changes in membrane thickness, which in turn affect the gating properties of ion channels in neurons. Interference with the hydrophobic portion of neuronal ion channel membrane proteins may be an important mechanism {05} {06}.


Other actions/effects:


Cardiovascular system effects:

Sevoflurane has several effects that serve to lower blood pressure. It depresses cardiac function, decreases cardiac contractility, and decreases peripheral vascular resistance {01} {07} {08} {66} in a manner similar to that of isoflurane {66}. These effects are dose-related; increasing the concentration of sevoflurane during maintenance of anesthesia results in a dose-dependent decrease in blood pressure {01} {07}. The effect of sevoflurane on the coronary arteries and the potential for “coronary steal” has been investigated in dogs. Sevoflurane administration to chronically instrumented dogs resulted in a reduced ratio of occluded/normal and stenotic/normal coronary artery flows. However, the ratios returned to normal when the arterial blood pressure and heart rate were restored to conscious values {67}.

Sevoflurane has little effect on heart rate or rhythm. At clinically useful doses, sevoflurane does not increase heart rate or myocardial oxygen consumption {07} {10} {11} {63}. At higher concentrations, sevoflurane may increase heart rate {66}. A study on the effects of sevoflurane on the arrhythmic response to epinephrine suggests that sevoflurane does not greatly sensitize the myocardium to the arrhythmogenic effect of catecholamines {09}.



CNS:

Electroencephalogram (EEG): Sevoflurane causes a dose-dependent decrease in EEG activity. In dogs and rabbits, EEG burst suppression occurs at doses of 1 MAC or higher {12} {13} {63}. Although sevoflurane is not believed to be epileptogenic, case reports describe clonic and tonic seizure-like movements and clinically silent electrical seizures during induction of anesthesia {14} {15} {73}.

Effect on intracranial pressure: Sevoflurane did not impair cerebral autoregulation of blood flow when studied in patients with ischemic cerebrovascular disease {16}. However, sevoflurane has the potential to increase intracranial pressure {12}.



Neuromuscular effects:

Sevoflurane impairs neuromuscular conduction and decreases muscle contractility. Sevoflurane may produce sufficient muscle relaxation to allow some types of surgery to be performed without a neuromuscular blocker {17} {63}.



Respiratory system effects:

Respiration: Sevoflurane depresses ventilation in a dose-dependent manner, with apnea occurring between 1.5 and 2 MAC. Surgical stimulation changes the threshold at which apnea occurs {18}. Sevoflurane increases carbon dioxide tension and decreases ventilatory response to increased carbon dioxide concentrations {19} {63}.

Effects on the airway: Sevoflurane results in a low incidence of respiratory irritation as evidenced by a low incidence of breath-holding, coughing, increased salivation, and laryngospasm during induction {01} {20} {21} {22}.


Absorption:

Sevoflurane is rapidly absorbed into the circulation via the lungs. Its solubility in the blood is low; for a given concentration of sevoflurane in the gas phase, only a small amount dissolved in the blood is necessary to achieve equilibrium between the alveolar partial pressure and the arterial partial pressure {01} {23}.

Biotransformation:

Approximately 5% of the sevoflurane dose is metabolized, primarily by cytochrome P450 2E1, with release of inorganic fluoride and carbon dioxide {24} {25} {26}. The plasma inorganic fluoride concentration is increased to > 95 mcg per dL (mcg/dL) (50 micromoles per L [micromoles/L]) following surgery of long duration {27} {28}.

Time to peak concentration:

The alveolar concentration of sevoflurane increases rapidly toward the inspired concentration. The ratio of alveolar concentration to inspired concentration increases more rapidly with nitrous oxide and desflurane than with sevoflurane but more rapidly with sevoflurane than with isoflurane and halothane {23}.

Time to peak effect:

Onset of anesthesia—Sevoflurane has a favorable rate of increase of the ratio of alveolar concentration to inspired concentration. When sevoflurane is used alone and is administered by conventional technique, induction is accomplished in 2 minutes. This time can be reduced by the addition of nitrous oxide or the use of a vital capacity breath technique. With the use of a vital capacity breath technique, induction can be accomplished in about 1 minute {29} {30}.

Duration of action:

Time to recovery—Recovery after discontinuation is rapid but is subject to interpatient variability. Recovery time is affected by the administered concentration and other CNS depressants used concurrently. Emergence from sevoflurane is more rapid than emergence from isoflurane, but less rapid than from desflurane {68}. Spontaneous eye opening, response to simple commands, extubation, and orientation are more quickly achieved with sevoflurane than with isoflurane {68}. However, time to later recovery events (walking, tolerating oral fluids, voiding, and home readiness) does not differ between isoflurane and sevoflurane or desflurane and sevoflurane {20} {31} {68}.

Elimination:
    Rapidly eliminated via exhalation. The metabolite is conjugated with glucuronic acid and eliminated via the urine. Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride. Up to 50% of fluoride is taken up into the bone. As compared to the half-life in healthy individuals, the fluoride ion half-life is prolonged in patients with renal function impairment (33 hours versus 21 hours) and slightly prolonged in patients with hepatic function impairment {01}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other halogenated ether hydrocarbons may be sensitive to sevoflurane also {01}.

Carcinogenicity

Studies have not been done {01}.

Mutagenicity

No mutagenic effect was observed in the Ames test. No chromosomal aberrations were induced in cultured mammalian cells. Problems in humans have not been documented {01}.

Pregnancy/Reproduction
Fertility—
Reproduction studies performed in rats and rabbits at doses of up to 1 minimum alveolar concentration (MAC) revealed no evidence of impaired fertility.

Pregnancy—
Sevoflurane crosses the placenta. Adequate and well-controlled studies have not been done in humans {01}.

Studies in pregnant rabbits and rats at doses of 0.3 MAC, the highest nontoxic dose, revealed no fetal damage {01}.

FDA Pregnancy Category B {01}.


Labor and delivery—

The safety of sevoflurane in labor and vaginal delivery has not been established. Sevoflurane was used as part of general anesthesia in 61 women undergoing elective cesarean section {01} {32} {69} {70} {71}. There was no harmful effect in any mother or neonate. There was no difference between sevoflurane and isoflurane in recovery characteristics, Apgar score, or Neurological and Adaptive Capacity Score {32}. In one study two of sixteen patients had poor spontaneous uterine contractions after receiving sevoflurane {69}.

Breast-feeding

It is not known if sevoflurane is distributed into breast milk. However, because of rapid washout, sevoflurane concentrations in milk are predicted to be below those found with other anesthetics. The concentrations of sevoflurane in milk are thought to be of no clinical importance 24 hours after anesthesia {01}.

Pediatrics

Due to its lack of pungency, sevoflurane is widely used in Japan for induction of anesthesia in pediatric patients. As compared to halothane, sevoflurane for induction is associated with a higher incidence of excitation {33}. In one study, this led to a longer time to intubation with sevoflurane {33}. The longer time to intubation was not seen in two other studies, perhaps due to differences in the speed with which maximum concentrations of anesthetic were reached {34} {35}.

Pediatric patients require a higher concentration of sevoflurane for maintenance of general anesthesia than that required by adults {01}.

Sevoflurane is associated with a higher incidence of emergence excitation in children than is halothane, perhaps due to earlier emergence and the resultant earlier experience of pain in children receiving sevoflurane {33} {36} {63}.


Geriatrics


MAC decreases with increasing age. The average concentration of sevoflurane to achieve MAC in a patient 80 years of age is approximately 50% of that required in a patient 20 years of age {01} {03}.

Older adults may be slower than younger adults in achieving full cognitive recovery from general anesthesia with sevoflurane {78}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Many of the following interactions have not been reported with sevoflurane. However, because they have been reported with other halogenated hydrocarbon anesthetics, the possibility of a significant interaction with sevoflurane must be considered.

Alcohol, chronic use    (anesthetic requirement may be increased; induction of cytochrome P450 2E1 hepatic enzymes increases the extent of metabolism of sevoflurane, increasing the production of inorganic fluoride {25})


» Aminoglycosides, systemic or
Anesthetics, parenteral-local or
Bacitracin or
» Capreomycin or
» Citrate-anticoagulated blood, massive transfusions of or
» Clindamycin or
Colistimethate sodium or
Colistin or
Lidocaine, systemic or
» Lincomycin, systemic or
» Neuromuscular blocking agents or
» Polymyxins, systemic or
Procaine, systemic or
Tetracyclines or
Trimethaphan (large doses)    (neuromuscular blocking activities of these medications may be additive to that of sevoflurane, with the degree of potentiation increasing as the concentration of sevoflurane is increased {37})


Amiodarone    (concurrent use with inhalation anesthetics may potentiate hypotension and increase the risk of atropine-resistant bradycardia {50} {82})


Antimyasthenics    (antimyasthenics may decrease the neuromuscular blocking activity of halogenated hydrocarbon anesthetics; also, the neuromuscular blocking activity of the anesthetic may interfere with the efficacy of antimyasthenics; neuromuscular blockade with vecuronium during sevoflurane anesthesia may be more difficult to reverse with neostigmine than when similar blockade is produced during isoflurane anesthesia {38})


Beta-adrenergic blocking agents, including ophthalmics    (severe hypotension may result because beta-blockade reduces the ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli {60})


Catecholamines, such as dopamine, epinephrine, or norepinephrine    (sevoflurane may cause some sensitization of the myocardium to the effects of catecholamines, increasing the risk of arrhythmias; this is similar to isoflurane's effect on the myocardium; sevoflurane sensitizes the myocardium much less than does halothane {09} {73})


CNS depression–producing medications, other, including those commonly used for preanesthetic medications, or induction or supplementation of anesthesia (see Appendix II )    (may cause increased CNS depression, respiratory depression, and/or hypotension, decrease the anesthetic requirement, and prolong the recovery from anesthesia {01})


Hypotension-producing medications (see Appendix II )    (hypotensive effects may be potentiated when these medications are used concurrently with an inhalation anesthetic)


Isoniazid and other cytochrome P450 2E1 hepatic enzyme inducers    (enzyme induction increases the extent of metabolism of sevoflurane, increasing the production of inorganic fluoride {41} {42}; increased plasma fluoride concentrations have been associated with renal function impairment with other volatile inhalation anesthetics)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]), serum and
Aspartate aminotransferase (AST [SGOT]), serum and
Bilirubin, serum, indirect and
Lactate dehydrogenase, serum    (values may be transiently increased; the increases are dose-related {27} {43} {44})


Blood urea nitrogen (BUN) and
Creatinine, serum and
Fluoride, serum    (concentration may be increased {01} {27} {28} {43} {45} {46})


Glucose, serum    (concentration may be increased {01})


Leukocytes    (counts may be increased {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Malignant hyperthermia, history of    (possible increased risk of malignant hyperthermia with sevoflurane {01}; malignant hyperthermia has been associated with the use of sevoflurane in both children and adults {47} {48} {49})


» Sensitivity to halogenated ether anesthetic agents    (possible increased risk of sensitivity to sevoflurane {01}; although not yet reported with sevoflurane, cases of immune-mediated hepatitis have been reported with similar inhalation anesthetics {79})


Risk-benefit should be considered when the following medical problems exist
Familial periodic paralysis or
Muscular dystrophy or
Myasthenia gravis or
Myasthenic syndrome or
Other neuromuscular disease leading to muscle weakness    (the neuromuscular blocking activity of sevoflurane may increase the risk of severe muscle weakness in patients with these conditions; although use of an inhalation anesthetic with substantial neuromuscular blocking activity may be safer than [and eliminate the need for] a neuromuscular blocking agent in these patients, caution is recommended {61})


Head injury or
Increased intracranial pressure or
Intracranial lesions, space-occupying    (sevoflurane may increase intracranial pressure to the same extent that isoflurane may {01} {12}; in a study on ten patients with ischemic cerebrovascular disease, carbon dioxide response and cerebral autoregulation were maintained under 0.88 MAC anesthesia {16})


Hepatic function impairment    (in patients with mild to moderate hepatic function impairment, administration of sevoflurane resulted in prolonged terminal disposition of fluoride, as evidenced by longer inorganic fluoride half-life than that observed in patients with normal hepatic function; there is no published clinical experience with use of sevoflurane in patients with severe hepatic function impairment {01})


Pulsed dye laser therapy for portwine stain    (sevoflurane anesthesia is associated with portwine stain fading and subsequent early termination of pulsed dye laser treatment, resulting in inadequate treatment of the stain; the incidence of portwine stain fade with sevoflurane is significantly higher than the incidence of fade with halothane, enflurane, or isoflurane {51})


Renal function impairment    (extended anesthesia with sevoflurane is associated with hyperfluorinemia; with methoxyflurane, hyperfluorinemia in excess of 95 mcg per dL [mcg/dL] [50 micromoles per L (micromoles/L)] has been associated with renal function impairment; a tendency toward decreased urine concentrating ability and increased urinary excretion of N-acetyl-beta-glucosaminidase [NAG] has been associated with the use of sevoflurane {40} {72}; serum fluoride concentrations in excess of 95 mcg/dL [50 micromoles/L] achieved with the use of sevoflurane have not been associated with frank renal failure {27} {28} {33} {45} {52} {53} {74}; reaction of sevoflurane with carbon dioxide [CO 2] absorbents is associated with the formation of compound A, a nephrotoxin in rats {54} {64}; the toxicity of compound A has not been established in humans {55}; although causality could not be established, transient nonoliguric renal failure was reported after a 25-year-old burn patient with previously normal renal function received sevoflurane three times within 2 weeks for debridement of burned tissue {39}; caution is recommended in patients with renal function impairment because of limited studies done in this patient population {80} {81})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


Note: Various organizations, including medical specialty societies, and institutions have established standards for the preprocedural, intraprocedural, and postprocedural care, evaluation, and monitoring of patients receiving various forms of anesthesia. The following recommendations represent the minimum standards established by the American Society of Anesthesiologists for monitoring the status of patients receiving general anesthesia. Individual patients may require additional monitoring. {62}

» Blood pressure and
» Body temperature and
» Cardiac/pulse rate and
» Cardiac rhythm and
» Pulse oximetry and
» Respiratory and ventilatory status    (continuous monitoring is advisable during anesthetic administration; respiratory depression and excessive decreases in blood pressure may be related to the depth of anesthesia and may be corrected by decreasing the inspired concentration of sevoflurane {62})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent (greater than 3%)
During induction by mask (adult patients)
    
Airway obstruction{01}
    
bradycardia{01}
    
breath-holding{01}
    
cough, increased{01}
    
hypotension{01}
    
laryngospasm{01}

During induction by mask (pediatric patients)
    
Breath-holding{01}
    
cough, increased{01}
    
hypotension{01}
    
tachycardia{01}

During induction by mask (adult and pediatric patients)
    
Agitation{01}

During maintenance and recovery (adult and pediatric patients)
    
Bradycardia{01}
    
excitement{33}{74}{83}
    
hypotension{01}


Incidence less frequent (1 to 3%)
During induction by mask (adult patients)
    
Tachycardia{01}

During induction by mask (pediatric patients)
    
Apnea{01}
    
laryngospasm{01}

During maintenance and recovery (adult and pediatric patients)
    
Breath-holding{01}
    
fever{01}
    
hypertension{01}
    
hypothermia{01}
    
laryngospasm{01}
    
tachycardia{01}


Incidence rare (less than 1%)
    
Acidosis{01}
    
arrhythmias{01}
    
bronchospasm{01}
    
hypoxia{01}
    
malignant hyperthermia{01}
    
seizures{14}{15}
    
syncope{01}
    
wheezing{01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent (greater than 3%)
During maintenance and recovery (adult and pediatric patients)
    
Cough{01}
    
dizziness{01}
    
drowsiness{01}
    
nausea{01}
    
salivation, increased{01}
    
shivering{01}
    
vomiting{01}


Incidence less frequent (1 to 3%)
During maintenance and recovery (adult and pediatric patients)
    
Headache{01}






Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The clinical effects of an overdose of sevoflurane represent an extension of its therapeutic effects. Some respiratory effects of increased depth of anesthesia (for example, respiratory depression and apnea) do not present difficulties if assisted or controlled ventilation is being used during the procedure. The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute effects
    
Apnea {18}{19}
    
bradycardia {07}{10}
    
cardiac arrest {01}{07}
    
circulatory collapse{01}{07}
    
circulatory depression {01}{07}
    
decreased cardiac contractility{08}
    
decreased peripheral vascular resistance{01}{07}
    
hypotension{01}{07}
    
respiratory depression {18}{19}


Treatment of overdose
Discontinuing sevoflurane, maintaining a patent airway, initiating assisted or controlled ventilation with oxygen, and maintaining adequate cardiovascular function with general measures of circulatory support {01}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Sevoflurane (Inhalation-Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to sevoflurane or other halogenated ether anesthetics

Pregnancy—Sevoflurane crosses the placenta
Other medications, especially aminoglycosides (systemic), capreomycin, citrate-anticoagulated blood (massive transfusions of), clindamycin, lincomycin, neuromuscular blocking agents, or polymyxins (systemic)
Other medical problems, especially a history of or genetic susceptibility to malignant hyperthermia

Proper use of this medication

Proper dosing

Precautions after receiving this medication
» Possibility of psychomotor impairment following anesthesia; for 24 hours following anesthesia, avoiding driving or performing other tasks requiring alertness and coordination

» Avoiding use of alcohol or other CNS depressants within 24 hours following anesthesia, unless specifically prescribed or otherwise authorized by physician or dentist


Side/adverse effects
Notifying physician if cough, dizziness, drowsiness, nausea, increased salivation, shivering, vomiting, or headache occurs or persists after discharge


General Dosing Information
Sevoflurane is to be administered only by trained anesthesiologists or nurse anesthetists {83}. Equipment and personnel for support of ventilation must be immediately available {01}.

The dosage of sevoflurane must be individualized according to surgical requirements; concurrent use of adjuvant medications and/or nitrous oxide; and patient variables, especially age. Anesthetic requirements are increased in young children and decreased in geriatric patients {03} {33} {35} {36}.

The dosage requirement for neuromuscular blockers may change with sevoflurane anesthesia. The dose of neuromuscular blocker administered for endotracheal intubation should not be decreased, because delayed intubation may result {01}. During maintenance of anesthesia with sevoflurane, the dose of neuromuscular blocker is likely to be lower than that required during anesthesia maintained with nitrous oxide and opioid agents {01}. Neuromuscular blockade with vecuronium during sevoflurane anesthesia may be more difficult to reverse with neostigmine than when similar blockade is produced during isoflurane anesthesia {38}.

Sevoflurane has a nonpungent odor and is associated with a low incidence of respiratory irritability, making it suitable for mask induction {01} {33} {35} {36} {63}.

Sevoflurane may be vaporized in a flow of oxygen or a nitrous oxide–oxygen mixture {01}. 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. Fresh gas flow rates below 2 L per minute (L/min) are not recommended {01}. A concern in low-flow systems is accumulation of compound A, a substance produced when sevoflurane interacts with carbon dioxide absorbents (e.g., soda lime or barium hydroxide) {56} {64}. Compound A has been found to be a dose-dependent nephrotoxin in rats {54} {75} {77}. The toxicity of compound A in humans has not been established.

During the maintenance of anesthesia, increasing the concentration of sevoflurane produces dose-dependent decreases in blood pressure. These hemodynamic changes may occur rapidly with sevoflurane due to its relative insolubility in blood. Excessive respiratory depression or decreases in blood pressure may be related to the depth of anesthesia and may be corrected by decreasing the inspired concentration of sevoflurane {01}.

No specific premedication is indicated or contraindicated with the use of sevoflurane. The decisions regarding premedication should be based on the judgment of the health care professional {01}.

Safety considerations for handling this medication
Acute overexposure of operating room personnel to sevoflurane may cause headache, dizziness, and, in extreme cases, unconsciousness.

The results of some epidemiological studies suggest a link between chronic exposure of operating room personnel to low concentrations of inhalation anesthetics (waste anesthetic gases [WAGs]) and increased health problems, including reproductive problems (increases in spontaneous abortions, stillbirths, and possibly birth defects) {57} {58}. Although a causal relationship has not been established, measures to minimize exposure are recommended {57} {58}. Such measures include maintaining adequate general ventilation in the operating room, using a well-designed and well-maintained scavenging system, and, by employment of careful work procedures and routine equipment maintenance, minimizing leaks and spills while the anesthetic is in use {57} {58}.

Although no specific work exposure limit has been established for sevoflurane, the National Institute for Occupational Safety and Health Administration has recommended an 8-hour, time-weighted average limit of 2 parts per million (ppm) for halogenated anesthetic agents in general. The limit for halogenated anesthetics coupled with nitrous oxide is 0.5 ppm {01}.

For treatment of adverse effects
Recommended treatment consists of the following

   • For malignant hyperthermic crisis—Discontinuation of possible triggering agents (such as inhalation anesthetics or succinylcholine), managing increased oxygen requirement, cooling the patient, and correcting fluid and electrolyte imbalances and metabolic acidosis. Dantrolene can be administered by rapid intravenous injection (see Dantrolene [Systemic] monograph) {01}.


Inhalation Dosage Forms

SEVOFLURANE

Usual adult dose
Anesthetic (general)


Inhalation, vaporized in a flow of oxygen or nitrous oxide and oxygen:
Induction—Dosage must be individualized according to patient response {01}.

Maintenance—Dosage must be individualized according to patient response. Surgical levels of anesthesia usually can be achieved with concentrations of 0.5 to 3% sevoflurane with or without concomitant use of nitrous oxide {01}.


Note: Anesthetic requirements decrease with increasing age. Minimum alveolar concentration (MAC) values for sevoflurane in oxygen are 2.6% for patients 25 years of age, 2.1% for patients 40 years of age, 1.7% for patients 60 years of age, and 1.4% for patients 80 years of age. Geriatric patients require lower doses of sevoflurane for induction and maintenance of anesthesia {01} {03}.



Usual pediatric dose
Anesthetic (general)


Inhalation, vaporized in a flow of oxygen or nitrous oxide and oxygen:
Induction—Dosage must be individualized according to patient response {01}.

Maintenance—Dosage must be individualized according to patient response. Surgical levels of anesthesia usually can be achieved with concentrations of 0.5 to 3% sevoflurane with or without concomitant use of nitrous oxide {01} {33} {36}.


Note: Anesthetic requirements decrease with increasing age. MAC values for sevoflurane in oxygen are 3.3% for neonates, 3% for infants less than 6 months of age, 2.8% for infants and children 6 months to 3 years of age, and 2.5% for children 3 to 12 years of age. MAC in premature neonates has not been determined {01}.
MAC in adolescents has not been determined. The adolescent dose for other inhalation anesthetics is slightly higher than the dose for adult patients {73} {81}.



Usual geriatric dose
Anesthetic (general)
Geriatric patients require lower doses of sevoflurane for induction and maintenance of anesthesia {01} {03}. See Usual adult dose.


Product(s) usually available:
U.S.—


[Ultane{01}]

Canada—


[Sevorane{65}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {01}.

Stability:
Stable at room temperature {01}. No discernible degradation occurs in the presence of acid or heat {01}. The only known degradation reaction in the clinical setting is through direct contact with carbon dioxide absorbents such as soda lime {01}. This reaction produces pentafluoroisopropenyl fluoromethyl ether, also known as compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether, also known as compound B {01}. The concentration of the degradants is inversely correlated with fresh gas flow rate {01} {56}.

With sevoflurane, unlike with desflurane, enflurane, and isoflurane, degradation of the anesthetic during use does not result in significant production of carbon monoxide {59}.



Revised: 12/11/1998



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  1. Panel comment, 2/96.
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