Adult: In surgical and diagnostic procedures: Initially, 6-9 mg/kg/hr infused over 3-5 minutes. Alternatively, 0.5-1 mg/kg via slow injection over 1-5 minutes. Maintenance: 1.5-4.5 mg/kg/hr via infusion. Additional 10-20 mg incremental bolus inj as 1% emulsion may be given if rapid increase in the depth of sedation is required. As 1% or 2% emulsion: In intensive care setting: Induction and maintenance: 0.3-4 mg/kg/hr via infusion over 5 minutes. Rate of administration may be individualised and titrated based on desired depth of sedation. Elderly: As 1% or 2% emulsion: Induction: Same as adult dose. Avoid rapid bolus inj. Maintenance: 80% of adult dose. Individualise dosage according to response. Child: As 1% emulsion for >1 month or as 2% emulsion for >3 years: In surgical and diagnostic procedures: 1-2 mg/kg given via infusion. Dose and rate of administration is adjusted according to the required depth of sedation and clinical response. Maintenance: 1.5-9 mg/kg/hr via infusion. May be supplemented with up to 1 mg/kg via bolus inj as 1% emulsion if rapid increase of depth of sedation is required.
Intravenous Induction and maintenance of general anaesthesia
Adult: As 1% emulsion given via IV inj or infusion or as 2% emulsion given via infusion: Induction: 40 mg every 10 seconds, titrated until clinical response is achieved. Usual dose: 1.5-2.5 mg/kg. Maintenance: 4-12 mg/kg/hr continuous infusion. Alternatively, 25-50 mg intermittent bolus inj of 1% emulsion. Target-controlled infusion (TCI) delivery system may also be used based on target blood concentrations, refer to detailed product guideline. Elderly: Induction: 20 mg every 10 seconds until onset of induction. Maintenance: 3-6 mg/kg/hr. Child: As 1% emulsion for >1 month given via infusion or intermittent bolus inj or as 2% emulsion for >3 years given via infusion: Induction: 2.5-4 mg/kg. Maintenance: 9-15 mg/kg/hr.
Contraindications
Sedation in ICU setting in children <16 years.
Special Precautions
Patient with lipid metabolism disorders such as hypertriglyceridaemia or pancreatitis, or risk of fat overload; cardiac impairment; pulmonary insufficiency or respiratory depression; increased intracranial pressure or impaired cerebral circulation; hypovolaemia, unstable haemodynamics, abnormal low vascular tone (e.g. sepsis); risk factors for PRIS (e.g. decreased oxygen delivery, sepsis, serious cerebral injury). Patient predisposed to zinc deficiency (e.g. diarrhoea, major sepsis, burns). ASA grade 3 or 4, debilitated and epileptic patient. Renal and hepatic impairment. Children and elderly. Pregnancy and lactation. Avoid abrupt discontinuation; taper infusion dose to prevent withdrawal (for prolonged infusions). Not recommended for obstetric anaesthesia including caesarean section deliveries.
Adverse Reactions
Significant: ECG effects (e.g. QT shortening/prolongation), hypertriglyceridaemia, hypotension, injection-site reaction, perioperative myoclonus (e.g. convulsions, opisthotonos), involuntary movement, Rarely, postoperative unconsciousness with or without an increase in muscle tone, anaphylaxis, hypersensitivity reactions Cardiac disorders: Cardiac arrhythmia, low cardiac output, tachycardia. Gastrointestinal disorders: Nausea, vomiting. Metabolism and nutrition disorders: Respiratory acidosis. Nervous system disorders: Headache. Psychiatric disorders: Depression, confusion. Respiratory, thoracic and mediastinal disorders: Cough, laryngospasm. Skin and subcutaneous tissue disorders: Rash, pruritus. Vascular disorders: Hypertension. Potentially Fatal: Propofol-related infusion syndrome (PRIS) (e.g. lactic acidosis, hyperlipidaemia, hyperkalaemia, rhabdomyolysis). Abuse and dependence.
Patient Counseling Information
This drug may impair ability to drive or operate machinery.
Monitoring Parameters
Monitor cardiac input, blood pressure, oxygen saturation (during monitored anaesthesia care sedation); ABG (prolonged infusions). Monitor signs and symptoms of PRIS. Monitor serum triglycerides prior to initiation of therapy for ICU sedation and every 3-7 days thereafter; zinc level after 5 days of treatment.
Overdosage
Symptoms: Cardiovascular and respiratory depression. Management: Provide artificial ventilation with oxygen for respiratory depression. Reposition patient by raising the legs and lowering the head; increase IV fluids flow rate or administering plasma expanders and pressor agents to manage cardiovascular depression.
Drug Interactions
Additive sedative/anaesthetic and cardiorespiratory depressant effect with other CNS depressants. Profound hypotension with rifampicin. Valproate may increase serum levels of propofol.
Food Interaction
Enhanced sedative effect with alcohol.
Action
Description: Mechanism of Action: Propofol is a short-acting, liphophilic general anaesthetic. . It is thought to produce sedative/anaesthetic effects through positive modulation of inhibitory function of the neurotransmitter GABA through the GABAA receptors and possibly reduced glutamatergic activity through NMDA receptor blockade. Onset: 9-51 seconds (average: 30 seconds). Duration: 3-10 minutes. Pharmacokinetics: Distribution: Crosses the placenta, enters breastmilk (small amounts). Volume of distribution: 2-10 L/kg; 60 L/kg (10-day infusion). Plasma protein binding: 97-99%. Metabolism: Metabolised in the liver to water-soluble sulfate and glucuronide conjugates. Excretion: Via urine (Approx 88% as metabolites, 40% as glucuronide metabolite); faeces (<2%). Elimination half-life: Initial: 40 minutes; Terminal: 4-7 hours, 24-72 hours (10-day infusion).
Chemical Structure
Propofol Source: National Center for Biotechnology Information. PubChem Database. Propofol, CID=4943, https://pubchem.ncbi.nlm.nih.gov/compound/Propofol (accessed on Jan. 23, 2020)
N01AX10 - propofol ; Belongs to the class of other general anesthetics.
References
Anon. Propofol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 24/05/2019.Buckingham R (ed). Propofol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 24/05/2019.Diprivan Emulsion for Injection (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 24/05/2019.
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