What is the appropriate dosing for Propofol (propofol) infusion?

From the Guidelines

Propofol infusion for sedation should be initiated at a dose of 5-50 mcg/kg/min (0.3-3 mg/kg/hr) and titrated to the desired level of sedation, with careful monitoring of patient response and vital signs, as recommended by the most recent and highest quality study 1. When administering propofol, it is essential to consider the patient's individual needs and medical history, as well as the potential risks and side effects associated with the drug.

• The loading dose for propofol is typically 1-2.5 mg/kg administered slowly over 1-2 minutes before starting the continuous infusion.
• Elderly, critically ill, or hemodynamically unstable patients generally require lower doses, starting at 5-10 mcg/kg/min.
• Propofol works by enhancing GABA activity in the brain, causing rapid sedation with a quick onset (30-60 seconds) and short recovery time.
• The drug is lipophilic and redistributes quickly, allowing for rapid awakening when discontinued.
• However, propofol can cause hypotension, respiratory depression, and pain at the injection site, and there is a risk of propofol infusion syndrome (PRIS) with prolonged administration of high doses (> 70 μg/kg/min) 1.
• To minimize the risk of PRIS, it is crucial to monitor patients closely for signs and symptoms such as worsening metabolic acidosis, hypertriglyceridemia, hypotension, and arrhythmias, and to discontinue the infusion promptly if suspected.
• Airway management equipment should always be readily available, and consideration should be given to administering the drug through a large vein with concurrent IV fluids to minimize pain and hypotension.
• According to the study published in Critical Care Medicine in 2013 1, the incidence of PRIS with propofol infusions is approximately 1%, and mortality from PRIS is high (up to 33%), making early recognition and discontinuation of propofol critically important.

From the FDA Drug Label

Adult Patients In adults, anesthesia can be maintained by administering propofol injectable emulsion by infusion or intermittent IV bolus injection The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections. Continuous Infusion Propofol injectable emulsion 100 mcg/kg/min to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery Maintenance by infusion of propofol injectable emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 mcg/kg/min to 200 mcg/kg/min) for the first 10 to 15 minutes Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 mcg/kg/min to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.

The appropriate dosing for Propofol (propofol) infusion is:

• Initial infusion rate: 100 mcg/kg/min to 200 mcg/kg/min
• Initial period (10-15 minutes): 150 mcg/kg/min to 200 mcg/kg/min
• Maintenance rate: 50 mcg/kg/min to 100 mcg/kg/min
• Adjustment: Infusion rates should be decreased 30% to 50% during the first half-hour of maintenance and adjusted to clinical responses 2.

For ICU sedation, the recommended dosing is:

• Initiation: 5 mcg/kg/min to 10 mcg/kg/min, increased by increments of 5 mcg/kg/min to 10 mcg/kg/min until desired level of sedation is achieved
• Maintenance: 5 mcg/kg/min to 50 mcg/kg/min, adjusted to clinical responses 2.

It is essential to titrate to clinical response and adjust the infusion rate according to the patient's condition and response to minimize undesirable cardiorespiratory depression 2.

From the Research

Appropriate Dosing for Propofol Infusion

The appropriate dosing for propofol infusion is a critical consideration to minimize the risk of propofol infusion syndrome (PRIS) and other complications.

• The recommended dose of propofol infusion varies, but experts suggest that doses ≥83 μg/kg/min or treatment duration ≥48 h are associated with an increased risk of developing PRIS 3.
• Another study recommends avoiding doses exceeding 4-5 mg/kg/h for long periods (>48 h) to minimize the risk of PRIS 4.
• A review of the literature suggests that PRIS can occur with lower doses and after shorter durations of sedation, and that steroids, vasopressors, and low carbohydrate intake may act as triggering factors 5.
• In patients with refractory status epilepticus, the use of propofol infusion has been associated with significant mortality and morbidity, particularly with prolonged use of large doses 6.
• A study comparing incremental bolus versus continuous infusion of propofol for deep sedation/general anesthesia during dentoalveolar surgery found that both groups received a mean maintenance dose of propofol exceeding 6 mg/kg/hr, but the continuous infusion group received a statistically greater maintenance dose 7.

Key Considerations

• Monitor patients closely for early signs of PRIS, including metabolic acidosis, cardiac dysfunction, hypertriglyceridemia, and rhabdomyolysis 3.
• Avoid using propofol infusion in susceptible patients, and consider alternative sedative agents 5.
• When using prolonged sedation with propofol, monitor arrhythmia and serum triglyceridemia levels closely 5.