Propofol

Registered South African indications:

• Induction and maintenance of general anaesthesia
• Sedation
• Conscious sedation

Contraindications

South African recommendations

1% IV injection or infusion

• Known hypersensitivity to the active substance propofol or to any of the excipients listed
• Propofol contains soybean oil and should not be used in patients who are hypersensitive to peanut or soya
• Children under the age of 3 years
• Appropriate care should be applied in patients with disorders of fat metabolism, patients predisposed to fat embolism, and in other conditions where lipid emulsions must be used cautiously
• Fat metabolism may be disturbed in conditions such as renal insufficiency, uncompensated diabetes mellitus, certain forms of liver insufficiency, metabolic disorders, severe trauma including long-bone and multiple fractures, and sepsis
• Neonates and premature infants
• Propofol must not be used for sedation of patients less than 16 years of age in the intensive care unit
• Propofol must not be used for sedation of children of all ages with croup or epiglottitis receiving intensive care

2% IV infusion

• Hypersensitivity to propofol or to any of the excipients
• Patients who are hypersensitive to peanut or soya as propofol 2% contains soya oil
• Children under the age of 3 years
• Patients of 16 years of age or younger for sedation in intensive care
• For the sedation of children of all ages with croup or epiglottitis receiving intensive care
• Pregnant women

Recommendations in other jurisdictions

• Hypersensitivity to the active substance, soybeans, peanuts, or to any of the other ingredients of the emulsion
• For the sedation of patients aged 16 years or younger as part of intensive care
• As anaesthesia in children under 3 years of age (2%)

Cautions

• Pregnancy (1%) (South African recommendations)
• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding
• Renal impairment
• Hepatic impairment 
• Cardiac dysfunction 
• Respiratory impairment
• Hypovolaemic
• Debilitated patients
• Acute alcohol consumption (within 8 hours of procedure)
• Seizure disorder
• Disorders of fat metabolism
• Electroconvulsive treatment
• Mitochondrial disease
• Administration by individual conducting the diagnostic or surgical procedure
• Prolonged use
• Predisposition to zinc deficiency
• Serious neurological injury 
• Sepsis
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Induction and maintenance of general anaesthesia
- As part of a balanced anaesthetic technique

Induction

• IV:1%: Unpremedicated and pre-medicated patients: <55 years: Initial: 1.5-2.5mg/kg (0.15-0.25ml/kg) (approx. 4ml every 10sec), as a slow bolus or infusion titrated against the response of the patient until clinical signs show onset of anaesthesia; Total dose required can be reduced by lower rates of admin. (20-50mg/min [2-5ml/min]); ≥55 years: Requirement is generally less; In patients of ASA Grades 3 and 4: Lower rates of admin. should be used approx. 20mg (2ml), every 10sec
• IV: 2%: Unpremedicated and pre-medicated patients: <55 years: Initial: 1.5-2.5mg/kg (0.075-0.125ml/kg) (approx. 40mg every 10sec), as an infusion titrated against the response of the patient until clinical signs show onset of anaesthesia; Total dose required can be reduced by lower rates of admin. (20-50mg/min [1-2.5ml/min]); ≥55 years: Requirement is generally less; In patients of ASA Grades 3 and 4: Lower rates of admin. should be used approx. 20mg (1ml), every 10sec 

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Propofol 2% should be used to induce anaesthesia by infusion and only in those patients who will receive propofol 2% for maintenance of anaesthesia

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Maintenance

• IV: 1%: 4-12mg/kg/hr (0.4-1.2ml/kg/hr), as an infusion usually maintains satisfactory anaesthesia; Average rate of administration varies between patients; Slightly higher rates of admin. may be required for 10-20min after induction of anaesthesia; As a guide, increments of 25-50mg (2.5-5ml), given as repeat boluses may be used
• IV: 2%: 4-12mg/kg/hr (0.2-0.6ml/kg/hr), as an infusion usually maintain satisfactory anaesthesia; Slightly higher rates may be required for 10-20min post induction

Sedation
- Of ventilated patients receiving intensive care, for up to 72hrs

1% and 2%

• IV: 0.3-4mg/kg/hr, as an infusion should achieve satisfactory sedation for up to 72hrs; Adjust infusion rate according to the depth of sedation required

- For surgical and diagnostic procedures

• IV: 2%: Initial: 0.5-1mg/kg, as an infusion over 1-5min to initiate sedation; Maintenance: 1.5-4.5mg/kg/hr, titrated to the desired level of sedation; In addition to the infusion: 10-20mg, given as a bolus may be used if a rapid increase in the depth of sedation is required; Patients in ASA Grades 3 and 4: Rate of admin. and dosage may need to be reduced

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Rates above 4mg/kg/hr are not recommended for sedation in adults during intensive care

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Conscious sedation
- For surgical and diagnostic procedures, provided there are adequate facilities for monitoring haemodynamic and oxygenation parameters and if administered by a qualified anaesthetist

• IV: 1%: Initial: 0.5-1mg/kg, as an infusion over 1-5min to initiate sedation; Maintenance: 1.5-4.5mg/kg/hr, titrated to the desired level of sedation; In addition to the infusion: 10-20mg, given as a bolus may be used if a rapid increase in the depth of sedation is required; Patients in ASA Grades 3 and 4: Rate of admin. and dosage may need to be reduced

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Propofol 1% can be used undiluted or diluted (can be diluted with 5% dextrose intravenous infusion only, in PVC infusion bags or glass infusion bottles. Propofol 2% must be used undiluted; It can be infused from glass bottles, plastic syringes, or pre-filled syringes. Use drop counters, syringe pumps, or volumetric infusion pumps for controlling infusion rates

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Bolus injection of propofol 2% is not recommended

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To provide sedation for surgical and diagnostic procedures rates of administration should be individualised and titrated to clinical response

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1%: A single infusion of propofol must not exceed 6 hours for general anaesthesia or 12 hours for intensive care sedation. The syringe or giving set and any unused portions should be discarded after the designated time. For general anaesthesia these should be discarded at the end of the surgical procedure, or at 6 hours, whichever is the sooner, and replaced as appropriate
2%: A single infusion of propofol must not exceed 12 hours for both general anaesthesia or intensive care sedation. At the end of the surgical procedure or at 12 hours, whichever is the sooner, both the reservoir of propofol 2% and the infusion line must be discarded and replaced as appropriate. The syringe or giving set and any unused portions should be discarded after the designated time

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If propofol 1% or 2% is transferred to a syringe or other container prior to administration, the handling procedures for “General anaesthesia” should be followed and the product should be discarded, and administration lines changed after 6 hours

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Supplementary analgesic agents are required in addition to propofol where analgesia is required 

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Where general anaesthesia with propofol is used simultaneously with a regional anaesthetic technique, lower doses of propofol may be required

Paed. forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Induction and maintenance of general anaesthesia
- As part of a balanced anaesthetic technique

Younger than 3 years

• Contraindicated

3 years and older

Induction

• IV: 1%: Admin. slowly until clinical signs indicate the onset of anaesthesia; Adjust the dose according to age/weight; Most patients >8 years: Likely to require approx. 2.5mg/kg body weight; Between 3-8 years: The requirement may be higher; Initial dose: 3mg/kg body weight; If necessary, additional doses in steps of 1mg/kg body weight can be administered; Increased risk (ASA Grades III and IV): Lower dosages are recommended due to lack of clinical experience
• IV: 2%: Admin. slowly until clinical signs indicate the onset of anaesthesia; Adjust the dose according to age/weight; Most patients >8 years: Likely to require approx. 2.5mg/kg (0.125 ml/kg), for induction; Between 3-8 years: The requirement may be higher; In patients of ASA Grades 3 and 4: Lower doses are recommended

Maintenance

• IV: 1%: Rate of admin. varies significantly between patients: 9-15mg/kg/hr (0.9-1.5ml/kg/hr), as an infusion or repeat bolus injections usually achieve satisfactory anaesthesia
• IV: 2%: Rate of admin. varies significantly between patients: 9-15mg/kg/hr (0.45-0.75ml/kg/hr), as an infusion usually achieve satisfactory anaesthesia

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Propofol 1% must not be used for sedation in children below 16 years of age, as its safety and efficacy have not been demonstrated. Propofol 1% is not recommended for conscious sedation in children, as safety and efficacy have not been demonstrated

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Propofol 2% is not recommended for sedation in children, as its safety and efficacy have not been demonstrated

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Propofol 1% can be administered via infusion or repeat bolus injection as needed to maintain the desired depth of anaesthesia

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Propofol 2% must be used undiluted and is not recommended for bolus injection. Use equipment such as drop counters, syringe pumps, or volumetric infusion pumps for controlling infusion rates. Propofol 2% can be infused from glass bottles, plastic syringes, or pre-filled syringes

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1%: A single infusion of propofol must not exceed 6 hours for general anaesthesia or 12 hours for intensive care sedation. The syringe or giving set and any unused portions should be discarded after the designated time. For general anaesthesia these should be discarded at the end of the surgical procedure, or at 6 hours, whichever is the sooner, and replaced as appropriate
2%: A single infusion of propofol must not exceed 12 hours for both general anaesthesia or intensive care sedation. At the end of the surgical procedure or at 12 hours, whichever is the sooner, both the reservoir of propofol 2% and the infusion line must be discarded and replaced as appropriate. The syringe or giving set and any unused portions should be discarded after the designated time

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If propofol 1% or 2% is transferred to a syringe or other container prior to administration, the handling procedures for “General anaesthesia” should be followed and the product should be discarded, and administration lines changed after 6 hours

Pregnancy

South African recommendations

• 1%: Caution; not recommended
• 2%: Contraindicated
• Propofol should not be used in pregnancy
• Propofol crosses the placenta and may be associated with neonatal depression. Propofol should not be used for obstetric anaesthesia
• Propofol has been used, however, during termination of pregnancy in the first trimester

Recommendations in other jurisdictions

• Caution; positive evidence of risk in animals studies
• The safety of propofol during pregnancy has not been proven and therefore, Propofol should only be used during pregnancy if absolutely necessary
• Propofol  crosses the placenta and may be associated with the depression of vital functions in newborns
• Propofol can be employed as anaesthesia in the case of termination of pregnancy
• High dosages (more than 2.5mg propofol/kg body mass for induction or 6mg propofol/kg of body mass per hour for maintenance of anaesthesia) should be avoided
• Studies in animals have shown reproductive toxicity

Breastfeeding

• Caution; not recommended
• Studies of breastfeeding mothers showed that small quantities of propofol are excreted in human milk. Women should therefore not breastfeed for 24 hours after the administration of propofol. Milk produced during this period should be discarded

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache 
• Epileptiform movements
• Unconsciousness
• Involuntary movements
• Euphoric mood
• Drug abuse
• Drug dependence  

Cardiovascular Disorders

• Bradycardia
• Pulmonary oedema
• Cardiac arrhythmia 
• Cardiac failure
• Hypotension  
• Thrombosis
• Phlebitis

Gastrointestinal Disorders

• Nausea and vomiting 
• Pancreatitis

Hepatobiliary Disorders

• Hepatomegaly  

Genitourinary Disorders

• Discolouration of urine
• Renal failure
• Sexual disinhibition

Endocrine and Metabolic Disorders

• Metabolic acidosis
• Hyperkalaemia
• Hyperlipidaemia 

Musculoskeletal Disorders

• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Injection site pain
• Tissue necrosis 

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis

• Central nervous system depressants 
• Rifampicin

• Vital signs

Propofol produces its sedative and anaesthetic effects by the positive modulation of the inhibitory function of the neurotransmitter gamma aminobutyric acid (GABA) through the ligand-gated GABA-A receptors.

Injection (per ml) 10mg

• B Braun Propol 1% (B Braun)
• Diprivan 1% (AstraZeneca) originator
• Fresenius Propoven (Fresenius)
• Milsia 1% (Biotech Laboratories)
• Provive 1% (Dezzo)
• Propofol 1% Fresenius (Fresenius) originator

Injection (per ml) 20mg

• Diprivan 2% (AstraZeneca) originator
• Propofol 2% Fresenius  (Fresenius) originator
• Propofol MCT/LCT 2 % Fresenius (Fresenius)