Drugs List

Therapeutic Indications

Uses

Anaesthesia - general - inhalation

Induction and maintenance of general anaesthesia.

Dosage

Due to the complexity and specialist nature of anaesthesia, specific dosing information on this agent is not included. When using this agent specialist literature, national guidelines and Trust policies should be consulted, to ensure appropriate dosage and assessment of all relevant patient factors.

Administration

For inhalation only using a vaporiser specifically calibrated for use with sevoflurane, with oxygen or oxygen plus nitrous oxide as the carrier gas.

Contraindications

History of fever due to halogenated anaesthesia
Predisposition to malignant hyperthermia
History of hepatic impairment due to halogenated anaesthesia
History of jaundice due to halogenated anaesthesia
History of leucocytosis due to halogenated anaesthesia
Long QT syndrome
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Predisposition to increased intracranial pressure
Predisposition to seizures
Breastfeeding
Coronary arteriosclerosis
Electrolyte imbalance
Haemodynamic instability
Hepatic disorder
Hepatic impairment
History of torsade de pointes
Hypotension
Hypovolaemia
Known or suspected mitochondrial disorder
Myasthenia gravis
Neuromuscular disorder
Pregnancy
Renal impairment

Correct electrolyte disorders before treatment
Advise patient not to drive or operate machinery within 24-48 hours of dose
Anti-arrhythmic therapy should be available
A patent airway and adequate oxygenation must be maintained
May interact with dry carbon dioxide absorbents - do not allow to dry out
Resuscitation facilities must be immediately available
To be administered by anaesthetist or a doctor trained in intensive care
Perform ECG before and during treatment
Monitor for malignant hyperthermia
Monitor respiratory function
Monitor serum electrolytes
Repeated exposure (especially < 3 months) linked to severe hepatotoxicity
May aggravate/provoke arrhythmias
May cause hyperkalaemia
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Reduce dose if arterial blood pressure falls significantly
Discontinue if malignant hyperthermia occurs

Hypotension and respiratory depression increase as the level of anaesthesia deepens.

Caution is advised in patients with renal impairment, as safety in these patients has not been established.

Caution is advised in patients with underlying hepatic conditions or taking medicines known to affect hepatic function, as post-operative hepatotoxcity has been reported rarely.

Consider using techniques to lower intra-cranial pressure (e.g hyperventilation) in patients at risk of intra-cranial pressure elevation.

Seizures have been reported in children, young adults and older adults, with or without predisposing risk factors. The depth of anaesthesia should be limited in children. In patients with predisposing risk factors, use of EEG may be considered.

Before patients leave the recovery room, their recovery from general anaesthesia should be carefully assessed, as rapid emergence from anaesthesia is generally seen with sevoflurane, early relief of postoperative pain may be required. Rapid emergence in children may be associated with agitation and a lack of co-operation.

The risk of hyperkalaemia and/or cardiac arrhythmias may be increased in patients with latent or overt neuromuscular disease, particularly Duchenne muscular dystrophy. Rapid treatment of hyperkalaemia and cardiac arrhythmias is advised in all patients. Investigation for latent neuromuscular disease is advised in patients with no prior history.

Pregnancy and Lactation

Pregnancy

Use sevoflurane with caution in pregnancy.

Animal studies have shown sevoflurane to have teratogenic potential, but at the time of writing there is limited published experience concerning the use of sevoflurane during human pregnancy. Caution is required in obstetric anaesthesia because sevoflurane has a relaxing effect on the uterus which could increase the risk of uterine bleeding. All anaesthetics have the potential to cause respiratory depression in newborns, and the manufacturer states that sevoflurane should only be used during pregnancy if clearly necessary.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use sevoflurane with caution in breastfeeding.

It is not known whether sevoflurane or its metabolites are excreted in human milk, and the effect on a nursing infant is unknown. Based on it's low molecular weight, it is likely that sevoflurane is excreted into breast milk, but Briggs (2015) suggests the risk to a nursing infant is low. The manufacturer recommends suspending breast-feeding and discarding breast milk for 48 hours after administration, however LactMed states that no waiting period or discarding of milk is necessary.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Acute renal failure
Agitation
Anaphylactic reaction
Anaphylactoid reaction
Apnoea
Arrhythmias
Asthma
Atrial fibrillation
Blood glucose disturbances
Bradycardia
Bronchospasm
Cardiac arrest
Cardio-respiratory depression
Chest discomfort
Chills
Complete AV block
Confusion
Contact dermatitis
Convulsions
Cough
Dizziness
Dyspnoea
Dystonia
Elevated serum potassium
Extrasystoles
Facial swelling
Fever
Glycosuria
Headache
Hepatic failure
Hepatic necrosis
Hepatitis
Hypersalivation
Hypersensitivity reactions
Hypertension
Hypotension
Hypothermia
Hypoxia
Increase in creatinine
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Increased serum inorganic fluoride
Laryngospasm
Leucocytosis
Leucopenia
Malignant hyperthermia
Nausea
Pruritus
Pulmonary oedema
Rash
Respiratory disorders
Somnolence
Tachycardia
Torsades de pointes
Twitching
Urinary retention
Urticaria
Vomiting
Wheezing

Presentation

Volatile liquid for inhalation containing sevoflurane.

Drugs List

Therapeutic Indications

Uses

Anaesthesia - general - inhalation

Induction and maintenance of general anaesthesia.

Dosage

Due to the complexity and specialist nature of anaesthesia, specific dosing information on this agent is not included. When using this agent specialist literature, national guidelines and Trust policies should be consulted, to ensure appropriate dosage and assessment of all relevant patient factors.

Administration

For inhalation only using a vaporiser specifically calibrated for use with sevoflurane, with oxygen or oxygen plus nitrous oxide as the carrier gas.

Contraindications

History of fever due to halogenated anaesthesia
Predisposition to malignant hyperthermia
History of hepatic impairment due to halogenated anaesthesia
History of jaundice due to halogenated anaesthesia
History of leucocytosis due to halogenated anaesthesia
Long QT syndrome
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Predisposition to increased intracranial pressure
Predisposition to seizures
Breastfeeding
Coronary arteriosclerosis
Electrolyte imbalance
Haemodynamic instability
Hepatic disorder
Hepatic impairment
History of torsade de pointes
Hypotension
Hypovolaemia
Known or suspected mitochondrial disorder
Myasthenia gravis
Neuromuscular disorder
Pregnancy
Renal impairment

Correct electrolyte disorders before treatment
Advise patient not to drive or operate machinery within 24-48 hours of dose
Anti-arrhythmic therapy should be available
A patent airway and adequate oxygenation must be maintained
May interact with dry carbon dioxide absorbents - do not allow to dry out
Resuscitation facilities must be immediately available
To be administered by anaesthetist or a doctor trained in intensive care
Perform ECG before and during treatment
Monitor for malignant hyperthermia
Monitor respiratory function
Monitor serum electrolytes
Repeated exposure (especially < 3 months) linked to severe hepatotoxicity
May aggravate/provoke arrhythmias
May cause hyperkalaemia
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Reduce dose if arterial blood pressure falls significantly
Discontinue if malignant hyperthermia occurs

Hypotension and respiratory depression increase as the level of anaesthesia deepens.

Caution is advised in patients with renal impairment, as safety in these patients has not been established.

Caution is advised in patients with underlying hepatic conditions or taking medicines known to affect hepatic function, as post-operative hepatotoxcity has been reported rarely.

Consider using techniques to lower intra-cranial pressure (e.g hyperventilation) in patients at risk of intra-cranial pressure elevation.

Seizures have been reported in children, young adults and older adults, with or without predisposing risk factors. The depth of anaesthesia should be limited in children. In patients with predisposing risk factors, use of EEG may be considered.

Before patients leave the recovery room, their recovery from general anaesthesia should be carefully assessed, as rapid emergence from anaesthesia is generally seen with sevoflurane, early relief of postoperative pain may be required. Rapid emergence in children may be associated with agitation and a lack of co-operation.

The risk of hyperkalaemia and/or cardiac arrhythmias may be increased in patients with latent or overt neuromuscular disease, particularly Duchenne muscular dystrophy. Rapid treatment of hyperkalaemia and cardiac arrhythmias is advised in all patients. Investigation for latent neuromuscular disease is advised in patients with no prior history.

Pregnancy and Lactation

Pregnancy

Use sevoflurane with caution in pregnancy.

Animal studies have shown sevoflurane to have teratogenic potential, but at the time of writing there is limited published experience concerning the use of sevoflurane during human pregnancy. Caution is required in obstetric anaesthesia because sevoflurane has a relaxing effect on the uterus which could increase the risk of uterine bleeding. All anaesthetics have the potential to cause respiratory depression in newborns, and the manufacturer states that sevoflurane should only be used during pregnancy if clearly necessary.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use sevoflurane with caution in breastfeeding.

It is not known whether sevoflurane or its metabolites are excreted in human milk, and the effect on a nursing infant is unknown. Based on it's low molecular weight, it is likely that sevoflurane is excreted into breast milk, but Briggs (2015) suggests the risk to a nursing infant is low. The manufacturer recommends suspending breast-feeding and discarding breast milk for 48 hours after administration, however LactMed states that no waiting period or discarding of milk is necessary.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Acute renal failure
Agitation
Anaphylactic reaction
Anaphylactoid reaction
Apnoea
Arrhythmias
Asthma
Atrial fibrillation
Blood glucose disturbances
Bradycardia
Bronchospasm
Cardiac arrest
Cardio-respiratory depression
Chest discomfort
Chills
Complete AV block
Confusion
Contact dermatitis
Convulsions
Cough
Dizziness
Dyspnoea
Dystonia
Elevated serum potassium
Extrasystoles
Facial swelling
Fever
Glycosuria
Headache
Hepatic failure
Hepatic necrosis
Hepatitis
Hypersalivation
Hypersensitivity reactions
Hypertension
Hypotension
Hypothermia
Hypoxia
Increase in creatinine
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Increased serum inorganic fluoride
Laryngospasm
Leucocytosis
Leucopenia
Malignant hyperthermia
Nausea
Pruritus
Pulmonary oedema
Rash
Respiratory disorders
Somnolence
Tachycardia
Torsades de pointes
Twitching
Urinary retention
Urticaria
Vomiting
Wheezing

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Sevoflurane. AbbVie Laboratories Limited. Revised March 2018.
Summary of Product Characteristics: Sevoflurane. Piramal Healthcare UK Limited. Revised August 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 April 2018

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Sevoflurane. Last revised: 26 April, 2016
Last accessed: 20 April 2018