Propofol injection 2%
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Emulsion for injection or infusion containing 1g propofol per 50ml (2%).
Drugs List
Therapeutic Indications
Uses
Induction and maintenance of anaesthesia
Sedation for surgical and diagnostic procedures
Sedation of ventilated patients receiving intensive care
Induction and maintenance of general anaesthesia in adults and children over 3 years.
Sedation of ventilated patients over 16 years receiving intensive care.
Sedation for surgical and diagnostic procedures in adults and children over 3 years.
Not licensed for all indications in all age groups.
Dosage
This monograph relates only to the specific indications of the 2% 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.
Some manufacturers state that propofol 2% may be administered for a maximum period of 7 days.
Propofol has no analgesic properties and therefore supplementary analgesic agents are generally required in addition.
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.
Adults
Doses should be adjusted according to the response of the patient. For patients aged over 55 years, see Elderly section.
Patients of ASA grades 3 and 4 or debilitated patients may require further reductions in dose and dose rate.
Induction of general anaesthesia
Some manufacturers state propofol 2% may be used to induce anaesthesia by intravenous infusion but only in those patients who will receive propofol 2% for maintenance of anaesthesia.
Propofol 2% should be titrated (approximately 1ml to 2ml (20 to 40mg) every 10 seconds against the response of the patient until the clinical signs show the onset of anaesthesia. Most adult patients are likely to require 1.5mg/kg to 2.5mg/kg of propofol 2%. The total dose required can be reduced by lower rates of administration (1ml/minute to 2.5ml/minute (20mg/minute to 50mg/minute)).
In patients of American Society of Anaesthesiologists (ASA) grades 3 and 4, especially those with cardiac impairment, lower rates of administration should be used (approximately 1ml (20mg) every 10 seconds). A suggested dose for debilitated patients is 1mg/kg to 1.5mg/kg.
Maintenance of anaesthesia
The required rate of administration varies considerably between patients, but rates in the region of 4mg/kg/hour to 12mg/kg/hour usually maintain satisfactory anaesthesia. A suggested reduced rate for debilitated patients is 3mg/kg/hour to 6mg/kg/hour.
Some manufacturers state that administration should be by continuous infusion only, others indicate bolus injection is also suitable.
Sedation of ventilated patients during intensive care
It is recommended that propofol 2% be given by continuous infusion when used to provide sedation for ventilated patients undergoing intensive care. The infusion rate should be adjusted according to the depth of sedation required, but rates in the region of 0.3mg/kg/hour to 4mg/kg/hour should achieve satisfactory sedation. Rates of infusion greater than 4mg/kg/hour are not recommended.
It is recommended that blood lipid levels be monitored should propofol be administered to patients thought to be at particular risk of fat overload. Administration of propofol should be adjusted appropriately if the monitoring indicates that fat is being inadequately cleared from the body. If the duration of sedation is in excess of 3 days, lipids should be monitored in all patients. If the patient is receiving other intravenous lipid concurrently (e.g. Total Parenteral Nutrition) a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the propofol 2% formulation. 1ml of propofol 2% contains approximately 0.1g of fat.
Administration of propofol by a 'Diprifusor' TCI system is not recommended for sedation during intensive care.
Sedation for surgical and diagnostic procedures
Most patients will require 0.5mg/kg to 1mg/kg over 1 to 5 minutes for onset of sedation.
Maintenance of sedation may be accomplished by titrating propofol 2% infusion to the desired level of sedation (most patients will require 1.5mg/kg/hour to 4.5mg/kg/hour). In addition to the infusion, bolus administration of 10mg to 20mg may be used if a rapid increase in depth of sedation is required.
Administration of propofol by a 'Diprifusor' TCI system is not recommended for sedation for surgical and diagnostic procedures.
Elderly
Patients of ASA grades 3 and 4 or debilitated patients may require further reductions in dose and dose rate.
Induction of general anaesthesia
In elderly patients, the dose requirement for induction of anaesthesia with propofol 2% is reduced. The reduction should take into account the physical status and age of the patient. The reduced dose should be given at a slower rate and titrated against the response.
A suggested dose in patients aged over 55 years is 1mg/kg to 1.5mg/kg at a rate of 20mg every 10 seconds until response.
Maintenance of anaesthesia
When propofol 2% is used for maintenance of anaesthesia, the rate of infusion should be reduced (e.g. a suggested reduction rate is 3mg/kg/hour to 6mg/kg/hour).
Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardio-respiratory depression.
See 'Dosage, Adult' section.
Sedation of ventilated patients during intensive care
When propofol is used for sedation, the rate of infusion should be reduced. Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardio-respiratory depression.
See 'Dosage, Adult' section.
Sedation for surgical and diagnostic procedures
When propofol 2% is used for sedation the rate of infusion should also be reduced. Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardio-respiratory depression. Alternatively propofol 1% may be used.
See 'Dosage, Adult' section.
Children
Propofol 2% is not recommended in children aged less than 3 years of age.
Administration of propofol by a 'Diprifusor' TCI system is not recommended in children. Lower dosage is recommended for children of ASA grades 3 and 4.
Induction of general anaesthesia
When used to induce anaesthesia in children, it is recommended that propofol 2% be given by slow infusion until the clinical signs show the onset of anaesthesia. The dose should be adjusted for age and/or weight.
Some manufacturers state that most patients over the age of 8 years require approximately 2.5mg/kg body weight for induction of anaesthesia. In younger children, dose requirements may be higher (2.5mg/kg to 4mg/kg body weight).
The following alternative dosing schedule may be suitable:
Children 17 to 18 years: 1.5mg/kg to 2.5mg/kg by intravenous infusion, at a rate of 20mg to 40 mg every 10 seconds until response.
Children 3 to 17 years: 2.5mg/kg to 4mg/kg by intravenous infusion, administered slowly until response.
Children under 3 years: Contraindicated.
Maintenance of anaesthesia
Some manufacturers state that for most patients over the age of 3 years that administration rates between 9mg/kg/hour to 15mg/kg/hour (administered by intravenous infusion) usually results in satisfactory anaesthesia. Some manufacturers also state that propofol 2% may be given by repeated intravenous bolus injection for the maintenance of anaesthesia.
The following alternative dosing schedule may be suitable:
Children 17 to 18 years: 4mg/kg/hour to 12mg/kg/hour by continuous intravenous infusion, adjusted according to response.
Children 3 to 17 years: 9mg/kg/hour to 15mg/kg/hour by continuous intravenous infusion, adjusted according to response.
Sedation of ventilated patients during intensive care
Manufacturers state safety has not been demonstrated for children under 16 years of age.
The following alternative dosing schedule may be suitable:
Child 16 to 18 years:
0.3mg/kg/hour to 4mg/kg/hour by continuous intravenous infusion, adjusted according to response.
Sedation for surgical and diagnostic procedures for children over 3 years
For onset of sedation, most paediatric patients require 1mg/kg to 2mg/kg of propofol 2%.
Maintenance of sedation can be achieved by titrating propofol 2% infusion to the desired level of sedation (most patients require 1.5mg/kg/hour to 9mg/kg/hour).
Maintenance of sedation for surgical and diagnostic procedures
The following alternative dosing schedule may be suitable:
Children 17 to 18 years: 1.5mg/kg/hour to 4.5mg/kg/hour by intravenous infusion for the maintenance of sedation. If a rapid increase in sedation is required, 10mg to 20mg by intravenous injection (using 0.5% or 1% propofol) may be given to supplement the infusion.
Children 3 - 17 years: 1.5mg/kg/hour to 9 mg/kg/hour by intravenous infusion, adjusted according to response.
Additional Dosage Information
Some manufacturers advise on target propofol concentrations.
Induction and maintenance of anaesthesia
Target propofol concentration should be titrated against the response of the patient in order to achieve the depth of anaesthesia required.
In adult patients under 55 years of age, anaesthesia can usually be induced with target propofol concentrations in the region of 4microgram/ml to 8microgram/ml. An initial target of 4microgram/ml is recommended in premedicated patients and in unpremedicated patients an initial target of 6microgram/ml is advised. Induction time with these targets is generally within the range of 60 to 120 seconds. Higher targets will allow more rapid induction of anaesthesia but may be associated with more pronounced haemodynamic and respiratory depression.
A lower target concentration should be used in patients over the age of about 55 years and in patients of ASA grades 3 and 4. The target concentration can then be increased in steps of 0.5microgram/ml to 1microgram/ml at intervals of 1 minute to achieve a gradual induction of anaesthesia.
Supplementary analgesia will generally be required and the extent to which target concentrations for maintenance of anaesthesia can be reduced will be influenced by the amount of concomitant analgesia administered. Target propofol concentrations in the region of 3microgram/ml to 6microgram/ml usually maintain satisfactory anaesthesia.
The predicted propofol concentration on waking is generally in the region of 1microgram/ml to 2microgram/ml and will be influenced by the amount of analgesia given during maintenance.
Sedation of ventilated patients during intensive care
A target blood propofol concentration in the range of 0.2microgram/ml to 2micrograms/ml has been suggested. Administration should begin at the lower end of this range which should be titrated against the response of the patient in order to achieve the desired depth of sedation.
Administration
Administration by intravenous infusion or intravenous injection.
Administration by repeated bolus injection is not recommended by the majority of manufacturers.
Some manufacturers state that propofol 2% may be administered for a maximum period of 7 days.
In order to reduce pain on initial injection, lidocaine may be injected immediately prior to the injection of propofol 2%.
When propofol 2% is used to maintain anaesthesia, it is recommended that equipment such as syringe pumps or volumetric infusion pumps should always be used to control infusion rates.
Microbiological filters are not recommended. If infusion sets with filters are used, these must be lipid permeable.
Contraindications
Children under 3 years
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
Some brands contain EDTA which may deplete zinc stores after prolonged use
Resuscitation facilities must be immediately available
To be administered by anaesthetist or a doctor trained in intensive care
Monitor blood lipid concentration if sedation exceeds 3 days
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
Some manufacturers states that propofol 2% should not be used for induction and maintenance of anaesthesia in children aged under 3 years, sedation during intensive care in children aged under 16 years or sedation for surgical and diagnostic procedures in children under 3 years.
Hypotension may occur and occasionally requires the use of intravenous fluids and a reduced rate of administration of propofol during the period of anaesthetic maintenance.
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 or other severe myocardial diseases 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 2%. 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.
Administration of propofol should be adjusted appropriately if the monitoring indicates that fat is being inadequately cleared from the body. If the patient is receiving other intravenous lipid concurrently (e.g. Total Parenteral Nutrition) a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the propofol 2% formulation, 1ml of propofol 2% contains approximately 0.1g of fat.
Some brands contain EDTA. EDTA is a chelator of metal ions, including zinc. The need for supplemental zinc should be considered during prolonged administration of propofol, particularly in patients predisposed to zinc deficiency, such as those with burns, diarrhoea and/or major sepsis.
Not recommended for use in electroconvulsive therapy.
Caution is advised where a procedure requires repeated doses or prolonged use of propofol (beyond three hours) in children under three years due to potential risk of neurotoxicity.
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, rhabdomyolysis, 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.
Propofol is contraindicated during pregnancy by some manufacturers. 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.
Animal studies indicate a risk of neurotoxicity following prolonged use (beyond three hours) or repeated doses of propofol.
Lactation
Use propofol with caution during breastfeeding.
The manufacturers recommend that mothers should stop breastfeeding and discard breast milk for 24 hours after administration of propofol. When a combination of anaesthetic agents is used for a procedure, extra caution is advised and follow the recommendations for the most problematic medication.
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: Diprivan 2%. AstraZeneca UK Limited. Revised April 2019.
Summary of Product Characteristics: Propofol-Lipuro 2%. B. Braun. Revised May 2017.
Summary of Product Characteristics: Propoven 2%. Fresenius Kabi. Revised November 2018.
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: 16 October 2019
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
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