Propofol is indicated for:

• Induction and maintenance of general anesthesia.
• Sedation in intensive care settings.
• Sedation during surgical and diagnostic procedures.

Propofol is a highly lipid-soluble, short-acting intravenous general anesthetic. It produces rapid onset of anesthesia, typically within 30 to 60 seconds. Recovery is usually quick, with most patients regaining consciousness without confusion or nausea and becoming fully oriented within a few minutes. Patients are often ready for discharge within a few hours. Unlike many other anesthetic agents, propofol does not significantly accumulate in the body during maintenance dosing, making it particularly suitable for prolonged sedation in intensive care.

Its pharmacokinetics can be described by a three-compartment model: rapid distribution from blood to tissues (half-life 2–3 minutes), rapid metabolic clearance (half-life 30–60 minutes), and a slower terminal phase involving elimination from less-perfused tissues. Its rapid onset is due to its high lipid solubility, allowing it to easily cross the blood-brain barrier and act on the central nervous system. Propofol is metabolized in the liver into inactive glucuronide and sulfate conjugates, which are excreted through urine. The dose, blood concentration, and duration of anesthesia are closely related.

Propofol is a sedative-hypnotic agent used for the induction and maintenance of anaesthesia or sedation. Intravenous administration of a therapeutic dose of propofol produces rapid onset of hypnosis with minimal excitation, typically within about 45 seconds from the start of injection (corresponding to one arm–brain circulation time). The mechanism of action involves enhancement of the inhibitory activity of the neurotransmitter gamma-aminobutyric acid (GABA) via GABA-A receptors. Propofol is a highly lipid-soluble, short-acting intravenous general anaesthetic. Induction of anaesthesia usually occurs within 15–45 seconds in most patients. Recovery is generally rapid, with patients regaining consciousness quickly and typically without confusion or nausea. Most individuals become fully oriented within a few minutes and are usually fit for discharge within a few hours. Unlike many other anaesthetic agents, propofol does not significantly accumulate during maintenance dosing, making it particularly suitable for sedation in intensive care settings.

Propofol demonstrates features that distinguish it from other agents:

• The clinical advantages of MCT/LCT formulations are superior compared to conventional LCT or MCT emulsions.
• Propofol technology results in approximately 30% less free, lipophilic, and low water-soluble drug fraction, which is associated with reduced pain on injection compared to aqueous formulations.
• It remains the only formulation proven to significantly reduce pain at the injection site.

Adults:

Induction of general anaesthesia: The dosage of Propofol should be titrated individually against the response of the patient. The ordinary initial dosage in adults is 40 mg (4 ml) by slow intravenous bolus injection at intervals of 10 seconds until the clinical signs show the onset of anaesthesia. The ordinary induction dose in healthy patient below 55 years of age is 2.2–2.5 mg/kg. A dose of 1.0–1.5 mg/kg is often sufficient for older patient. Lower doses, most often 20 mg (2 ml) at intervals of 10 seconds, are recommended for patient of ASA grades 3 and 4.

Maintenance of general anaesthesia: Anaesthesia can be maintained by administering Propofol either by continuous infusion or by repeat bolus injections to maintain sufficient anaesthesia.

Continuous infusion: The required rate of infusion varies considerably between patients. At the onset of anaesthesia (during roughly the first 10–20 minutes), some patient may require a slightly higher infusion rate (8–10 mg/kg/h). However, sufficient anaesthesia is normally achieved by infusing 4–6 (up to 12) mg/kg/h of Propofol. Repeat bolus injections: 25–50 mg (2.5–5.0 ml) bolus injections, depending on response.

Sedation during intensive care: A bolus injection of 1.0–2.0 mg/kg should be given first, followed by continuous infusion adjusted according to required degree of sedation. An infusion rate of 0.3–4 mg/kg/h is usually sufficient.

Sedation for surgical and diagnostic procedures: Dosages shall be adjusted individually. Sufficient sedation for surgical and diagnostic procedures can usually be achieved by administering initially 0.5–1 mg/kg during 1–5 minutes, and maintained by continuous at a rate of 1–4.5 mg/kg/h. Bolus doses of 10–20 mg can be given in addition, should deeper sedation be suddenly required. Lower doses of Propofol are often sufficient for patient of ASA grades 3 and 4.

Children:

Propofol is not recommended for use in children less than 3 years of age as its safety has not been demonstrated.

Induction of general anaesthesia: Dosage of Propofol in children shall be adjusted for weight and age. The mean induction dose in children over 8 years is 2.5 mg/kg, given by slow intravenous injection until the clinical signs show the onset of anaesthesia. Younger children may need slightly higher doses of propofol per kilogram of weight. Lower dosages are recommended for children of ASA grades 3 and 4.

Maintenance of general anaesthesia: Anaesthesia can be maintained by administering Propofol either by continuous infusion or by repeat bolus injections. Dosage shall be adjusted individually, but an infusion rate of 9–15 mg/kg/h is usually sufficient to achieve satisfactory anaesthesia.

Sedation during intensive care, surgical diagnostic procedures: Propofol is not recommended for sedation in children as its efficacy and safety have not been demonstrated. Although no causal relationship has been established, serious adverse events (including fatalities) have been reported in cases, where propofol has been used against recommendations. Adverse events have most commonly been seen in children with respiratory tract infections given doses in excess of those recommended for adults.

Administration

Method of administration: In order to reduce pain on injection, the induction dose of propofol may be mixed immediately before injection into the plastic syringe with lidocaine injection 10 mg/ml injection, in a ratio of 1 part of lidocaine injection for 20 parts of Propofol.

Propofol can be administered either undiluted or diluted for infusion. Before injection or dilution, each ampoule or vial shall be inspected for any irregularity. Should any changes be observed, the product shall not be used. Suitable equipment shall be used to ensure correct rate of infusion. Volumetric infusion pumps and syringe pumps, for example, are suitable for this purpose. The ordinary infusion set used alone is not sufficient to prevent accidental overdosage reliably enough.

Compatibility: Propofol may be diluted only with 5% dextrose infusion. Dilution shall not exceed 1 in 5 (containing 2 mg/ml Propofol) and shall be prepared in a PVC infusion bag or glass infusion bottle. If a PVC infusion bag is used, the bag should be full and the dilution be prepared by withdrawing a volume of infusion fluid and replacing it with an equal volume of Propofol. Special attention shall be paid to preparing the dilution aseptically, immediately before administration. Any diluted solution shall be used within 6 hours of preparation. Any remaining solution shall be discarded.

Propofol can be safely used with spinal and epidural anesthesia, as well as with premedications, muscle relaxants, inhalational anesthetics, and analgesics without significant incompatibility. When used alongside local anesthetic techniques, reduced doses of propofol may be sufficient. At clinical doses, propofol does not suppress adrenocortical hormone production. However, concurrent administration with opioids may enhance respiratory depression.

Propofol is contraindicated in patients with known hypersensitivity to propofol or any component of the formulation.

Local: Propofol is generally well tolerated. The most common adverse effect is pain at the injection site, which can be minimized by mixing with lidocaine or administering into larger veins. Thrombosis and phlebitis are rare.

General: Hypotension and temporary apnea may occur during induction, especially in patients with poor health status. Rarely, seizures, involuntary movements, dystonic reactions, and pulmonary edema have been reported. During recovery, headache, nausea, and occasionally vomiting may occur, along with transient impairment of consciousness. Hypersensitivity reactions such as anaphylaxis, bronchospasm, edema, and facial redness have been observed. Cardiac arrest has been reported in some cases. Long-term use may cause harmless green or reddish-brown urine discoloration due to metabolites. Altered sexual behavior may also occur.

Due to limited clinical data, propofol should not be used during pregnancy. It crosses the placenta and is therefore not recommended for obstetric anesthesia. Safety in breastfeeding women has not been established.

Propofol should be administered only by specialists trained in anaesthesiology or under their direct supervision. The physician performing a surgical or diagnostic procedure should not be responsible for administering propofol. Adequate resuscitation facilities must be readily available in the treatment area in case of complications. During administration, patients should be continuously monitored for early signs of hypotension, airway obstruction, hypoventilation, or inadequate oxygenation. Particular care is required in patients receiving propofol sedation for procedures without assisted ventilation. Caution is advised when using propofol in patients with cardiac, respiratory, renal, or hepatic impairment. Patients with hypovolaemia or poor general condition are also at increased risk. As propofol does not possess vagolytic activity, bradycardia and even asystole may occur. The use of an anticholinergic agent prior to induction and during maintenance of anaesthesia should be considered, especially when propofol is combined with other agents that may induce bradycardia or in conditions where vagal tone is predominant. Since propofol is formulated as a lipid emulsion, caution is necessary in patients with severe disorders of fat metabolism, such as pathological hyperlipidaemia. If propofol is administered in situations where excessive fat intake may pose a risk, blood lipid levels should be monitored and the dosage adjusted accordingly. When other parenteral lipid emulsions are given concurrently, the lipid content of propofol (0.1 g/mL) should be included in the total fat intake calculation.

In patients with epilepsy, propofol may increase the risk of convulsions. Propofol does not provide adequate analgesia on its own; therefore, additional analgesic agents should be administered as required. Full recovery from general anaesthesia must be ensured before discharge. It should also be considered that residual effects of general anaesthesia may impair the patient’s ability to understand or follow postoperative instructions.

Pediatric Use: Not recommended for children under 3 years due to lack of established safety.

Overdose may lead to cardiorespiratory depression. Management includes airway support, oxygen-assisted ventilation, and cardiovascular support such as positioning, vasopressors, or fluid therapy if required.

General intravenous anesthetic

Store below 25°C. Do not freeze. Discard any unused portion.