Drugs List

Therapeutic Indications

Uses

Induction of anaesthesia
Sedation for surgical and diagnostic procedures

Induction of general anaesthesia in adults and children over 1 month.

Induction of sedation for surgical and diagnostic procedures in adults and children over 1 month.

Short term sedation for surgical and diagnostic procedures, alone or in combination with local or regional anaesthesia, in adults only.

Not licensed for all indications in all age groups.

Administration

Administered by intravenous injection or by intravenous infusion. For infusion, suitable infusion control devices should be used (e.g. volumetric pump).

The manufacturer states that propofol 0.5% may be administered for a maximum period of 1 hour.

In order to reduce pain on initial injection, propofol 0.5% may be mixed with preservative-free lidocaine injection 1%.

Microbiological filters are not recommended. If infusion sets with filters are used, these must be lipid permeable.

Contraindications

Neonates

Precautions and Warnings

Severe obesity
Breastfeeding
Cardiac impairment
Disorder of lipid metabolism
Epileptic disorder
Hepatic impairment
Hypotension
Hypovolaemia
Pregnancy
Raised intracranial pressure
Renal impairment
Respiratory impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains arachis (peanut oil), soya or soya derivative
Resuscitation facilities must be immediately available
To be administered by anaesthetist or a doctor trained in intensive care
Monitor blood lipid concentration in all patients at risk of fat overload
Monitor cardio-respiratory function
Monitor patients for hypotension,airway obstruction, oxygen desaturation
Potential for drug abuse
Discontinue immediately if signs of Propofol Infusion Syndrome occur
Increases risk of relative vagal overactivity
Onset of convulsions may be delayed-caution especially after day surgery
Not licensed for all indications in all age groups
Avoid alcohol before and at least 8 hours after administration
Breastfeeding: Do not breastfeed & discard milk for 24 hours after therapy

Use with caution in patients with epilepsy as there may be an increased risk of seizures. The administration rate of propofol should be reduced in these patients. An epileptic patient should have received antiepileptic medication before anaesthesia is induced.

Convulsions have been reported in both those with and without a history of epilepsy. Use with caution after day surgery, since the onset of convulsions can be delayed. Such reactions can occur hours or even days after termination of propofol administration. Propofol should be used with caution when used to sedate patients undergoing procedures where spontaneous movements are particularly undesirable e.g. ophthalmic surgery. Extreme care is required in surgery of the mouth, pharynx or larynx and in patients with acute circulatory failure (shock) or fixed cardiac output.

Before propofol is administered, hypovolaemia, cardiac impairment, circulatory depression or respiratory impairment should be corrected if possible. Patients with severe cardiac impairment should be treated with extreme caution and under intensive monitoring.

An adequate period is needed prior to discharge of the patient to ensure full recovery after use of propofol 0.5%. The development of period of post-operative unconsciousness may be accompanied by an increase in muscle tone following treatment with propofol. This may or may not be preceded by a period of wakefulness.

Concomitant use of other central nervous system depressants e.g. alcohol, other general anaesthetics, opioid analgesics will result in accentuation of their sedative effects. Respiratory or cardiovascular depression may occur when propofol is given along with other central nervous system depressants. Concomitant use of benzodiazepines, parasympatholytic agents and other anaesthetics has been reported to prolong the anaesthesia and to reduce the respiration rate.

Intravenous administration of an anticholinergic agent before induction, or during maintenance of anaesthesia should be considered, especially in situations where vagal tone is likely to predominate, or when propofol is used in conjunction with other agents likely to cause bradycardia. The risk of relative vagal over activity may be increased because propofol lacks vagolytic activity which has been associated with reports of bradycardia (occasionally profound) and also asystole.

If the patient is receiving other intravenous lipid concurrently, a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the propofol 0.5% formulation, 1ml of propofol 0.5% contains approximately 0.1g of fat.

Severely obese patients require higher doses of propofol to produce an adequate effect. There may consequently be an increased risk of haemodynamic effects in these patients.

Propofol used for sedation in intensive care units has been associated with a combination of metabolic derangements and organ system failure known as Propofol Infusion Syndrome. Symptoms of Propofol Infusion Syndrome include metabolic acidosis, rhabomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, cardiac arrhythmia, Brugada-type ECG and rapidly progressive cardiac failure. Risks include decreased oxygen delivery to tissues, serious neurological injury, sepsis, high doses or combination with vasoconstrictors, steroids and/or inotropes. Propofol must be immediately discontinued if the above symptoms occur.

Pregnancy and Lactation

Pregnancy

Use propofol with caution during pregnancy.

The manufacturer does not recommend using propofol during pregnancy. However, Schaefer (2007) concludes that propofol may be used in obstetrics to initiate anaesthesia for operations during pregnancy and labour. Newborns should be observed for a depressive effect on the breathing if used in labour. Doses above 2.5mg/kg for induction of anaesthesia or 6mg/kg/hour for maintenance of anaesthesia should not be exceeded.

At the time of writing, the safety of propofol administration during human pregnancy has not been established. Propofol crosses the placenta with blood cord levels at term approximately 70% those of maternal blood. As propofol crosses the placenta it may be associated with neonatal respiratory depression, particularly in the third trimester. Embryonic toxicity studies in rats and rabbits showed no teratogenic effects and suggest low risk.

Lactation

Use propofol with caution during breastfeeding.

The manufacturer recommend that mothers should stop breastfeeding and discard breast milk for 24 hours after administration of propofol.

Propofol enters breast milk in small amounts and with a short half life of 30 to 60 minutes is not expected to be absorbed by the infant in significant amounts (Schaefer). The percentage of propofol excreted into breast milk, when compared to placental transfer, is considered negligible.

Side Effects

Anaphylaxis
Angioedema
Apnoea
Arrhythmias
Asystole
Bradycardia
Bronchospasm
Brugada ECG pattern
Cardiac failure
Convulsions
Cough
Discolouration of urine
Disinhibition
Dyskinesia
Dystonia
Erythema
Euphoria
Fever
Flushing
Headache
Hepatomegaly
Hiccups
Hyperkalaemia
Hyperlipidaemia
Hypersensitivity reactions
Hyperventilation
Hypotension
Local pain
Metabolic acidosis
Myoclonus
Nausea
Opisthotonos
Pancreatitis
Phlebitis
Pulmonary oedema
Quincke's oedema
Renal failure
Respiratory depression
Rhabdomyolysis
Sensation of cold
Shivering
Spontaneous movements
Tachycardia
Thrombosis
Tissue damage
Unconsciousness
Vertigo
Vomiting

Presentation

Emulsion for injection or infusion containing 100mg propofol per 20ml (0.5%)

Drugs List

Therapeutic Indications

Uses

Induction of anaesthesia
Sedation for surgical and diagnostic procedures

Induction of general anaesthesia in adults and children over 1 month.

Induction of sedation for surgical and diagnostic procedures in adults and children over 1 month.

Short term sedation for surgical and diagnostic procedures, alone or in combination with local or regional anaesthesia, in adults only.

Not licensed for all indications in all age groups.

Dosage

This monograph relates only to the specific indications of the 0.5% propofol injection or infusion.Different strength preparations of propofol are available for other specific uses and the separate monographs should be consulted for further information.

Circulatory and respiratory functions should be monitored constantly (e.g. ECG, pulse rate). Facilities for the maintenance of a patent airway, for artificial ventilation, oxygen enrichment and other resuscitation facilities must be immediately available at all times.

The manufacturer states that propofol 0.5% may be administered for a maximum period of 1 hour.

Individual requirements vary and the recommended dosages are only a guide. Smaller doses are indicated in ill, shocked or debilitated patients and in significant hepatic impairment.

Propofol has no analgesic properties and therefore supplementary analgesic agents are generally required in addition.

Adults

Elderly

Children

Neonates

Additional Dosage Information

Administration

Administered by intravenous injection or by intravenous infusion. For infusion, suitable infusion control devices should be used (e.g. volumetric pump).

The manufacturer states that propofol 0.5% may be administered for a maximum period of 1 hour.

In order to reduce pain on initial injection, propofol 0.5% may be mixed with preservative-free lidocaine injection 1%.

Microbiological filters are not recommended. If infusion sets with filters are used, these must be lipid permeable.

Contraindications

Neonates

Precautions and Warnings

Severe obesity
Breastfeeding
Cardiac impairment
Disorder of lipid metabolism
Epileptic disorder
Hepatic impairment
Hypotension
Hypovolaemia
Pregnancy
Raised intracranial pressure
Renal impairment
Respiratory impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains arachis (peanut oil), soya or soya derivative
Resuscitation facilities must be immediately available
To be administered by anaesthetist or a doctor trained in intensive care
Monitor blood lipid concentration in all patients at risk of fat overload
Monitor cardio-respiratory function
Monitor patients for hypotension,airway obstruction, oxygen desaturation
Potential for drug abuse
Discontinue immediately if signs of Propofol Infusion Syndrome occur
Increases risk of relative vagal overactivity
Onset of convulsions may be delayed-caution especially after day surgery
Not licensed for all indications in all age groups
Avoid alcohol before and at least 8 hours after administration
Breastfeeding: Do not breastfeed & discard milk for 24 hours after therapy

Use with caution in patients with epilepsy as there may be an increased risk of seizures. The administration rate of propofol should be reduced in these patients. An epileptic patient should have received antiepileptic medication before anaesthesia is induced.

Convulsions have been reported in both those with and without a history of epilepsy. Use with caution after day surgery, since the onset of convulsions can be delayed. Such reactions can occur hours or even days after termination of propofol administration. Propofol should be used with caution when used to sedate patients undergoing procedures where spontaneous movements are particularly undesirable e.g. ophthalmic surgery. Extreme care is required in surgery of the mouth, pharynx or larynx and in patients with acute circulatory failure (shock) or fixed cardiac output.

Before propofol is administered, hypovolaemia, cardiac impairment, circulatory depression or respiratory impairment should be corrected if possible. Patients with severe cardiac impairment should be treated with extreme caution and under intensive monitoring.

An adequate period is needed prior to discharge of the patient to ensure full recovery after use of propofol 0.5%. The development of period of post-operative unconsciousness may be accompanied by an increase in muscle tone following treatment with propofol. This may or may not be preceded by a period of wakefulness.

Concomitant use of other central nervous system depressants e.g. alcohol, other general anaesthetics, opioid analgesics will result in accentuation of their sedative effects. Respiratory or cardiovascular depression may occur when propofol is given along with other central nervous system depressants. Concomitant use of benzodiazepines, parasympatholytic agents and other anaesthetics has been reported to prolong the anaesthesia and to reduce the respiration rate.

Intravenous administration of an anticholinergic agent before induction, or during maintenance of anaesthesia should be considered, especially in situations where vagal tone is likely to predominate, or when propofol is used in conjunction with other agents likely to cause bradycardia. The risk of relative vagal over activity may be increased because propofol lacks vagolytic activity which has been associated with reports of bradycardia (occasionally profound) and also asystole.

If the patient is receiving other intravenous lipid concurrently, a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the propofol 0.5% formulation, 1ml of propofol 0.5% contains approximately 0.1g of fat.

Severely obese patients require higher doses of propofol to produce an adequate effect. There may consequently be an increased risk of haemodynamic effects in these patients.

Propofol used for sedation in intensive care units has been associated with a combination of metabolic derangements and organ system failure known as Propofol Infusion Syndrome. Symptoms of Propofol Infusion Syndrome include metabolic acidosis, rhabomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, cardiac arrhythmia, Brugada-type ECG and rapidly progressive cardiac failure. Risks include decreased oxygen delivery to tissues, serious neurological injury, sepsis, high doses or combination with vasoconstrictors, steroids and/or inotropes. Propofol must be immediately discontinued if the above symptoms occur.

Pregnancy and Lactation

Pregnancy

Use propofol with caution during pregnancy.

The manufacturer does not recommend using propofol during pregnancy. However, Schaefer (2007) concludes that propofol may be used in obstetrics to initiate anaesthesia for operations during pregnancy and labour. Newborns should be observed for a depressive effect on the breathing if used in labour. Doses above 2.5mg/kg for induction of anaesthesia or 6mg/kg/hour for maintenance of anaesthesia should not be exceeded.

At the time of writing, the safety of propofol administration during human pregnancy has not been established. Propofol crosses the placenta with blood cord levels at term approximately 70% those of maternal blood. As propofol crosses the placenta it may be associated with neonatal respiratory depression, particularly in the third trimester. Embryonic toxicity studies in rats and rabbits showed no teratogenic effects and suggest low risk.

Lactation

Use propofol with caution during breastfeeding.

The manufacturer recommend that mothers should stop breastfeeding and discard breast milk for 24 hours after administration of propofol.

Propofol enters breast milk in small amounts and with a short half life of 30 to 60 minutes is not expected to be absorbed by the infant in significant amounts (Schaefer). The percentage of propofol excreted into breast milk, when compared to placental transfer, is considered negligible.

Side Effects

Anaphylaxis
Angioedema
Apnoea
Arrhythmias
Asystole
Bradycardia
Bronchospasm
Brugada ECG pattern
Cardiac failure
Convulsions
Cough
Discolouration of urine
Disinhibition
Dyskinesia
Dystonia
Erythema
Euphoria
Fever
Flushing
Headache
Hepatomegaly
Hiccups
Hyperkalaemia
Hyperlipidaemia
Hypersensitivity reactions
Hyperventilation
Hypotension
Local pain
Metabolic acidosis
Myoclonus
Nausea
Opisthotonos
Pancreatitis
Phlebitis
Pulmonary oedema
Quincke's oedema
Renal failure
Respiratory depression
Rhabdomyolysis
Sensation of cold
Shivering
Spontaneous movements
Tachycardia
Thrombosis
Tissue damage
Unconsciousness
Vertigo
Vomiting

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: October 2019

Reference Sources

Committee on Safety of Medicines. Propofol and delayed convulsions. Current Problems in Pharmacovigilance (1992) 35: 2.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Injectable Medicines Administration Guide, 2nd edition (2007) UCL NHS Foundation Trust. Blackwell Publishing, Oxford.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale,T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Propofol-Lipuro 0.5%. B. Braun. Revised May 2017.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 September 2017

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
Propofol. Last revised: August 14, 2012
Last accessed: November 28, 2012