From the Guidelines
Propofol is a highly effective sedative medication that should be used with caution due to its potential for respiratory depression, hypotension, and propofol infusion syndrome, and its administration should be guided by the most recent clinical practice guidelines, such as those published in 2013 1.
Key Characteristics of Propofol
- Propofol is an IV sedative that binds to multiple receptors in the central nervous system, including GABAA, glycine, nicotinic, and M1 muscarinic receptors, resulting in sedative, hypnotic, anxiolytic, amnestic, antiemetic, and anticonvulsant properties 1.
- It has a rapid onset of action, typically within 30-60 seconds, and a short duration of effect, lasting 4-8 minutes, making it ideal for short procedures 1.
- The standard induction dose is 1.5-2.5 mg/kg, followed by maintenance infusions of 4-12 mg/kg/hr as needed 1.
Side Effects and Contraindications
- Common side effects include hypotension, pain at injection site, respiratory depression, and temporary apnea 1.
- Less common effects include propofol infusion syndrome (with prolonged high-dose use), allergic reactions, and paradoxical excitation 1.
- Propofol is contraindicated in patients with allergies to egg or soybean oil, as it contains these components 1.
Clinical Use and Monitoring
- Propofol should be administered by trained healthcare providers with appropriate monitoring equipment due to its potential for rapid respiratory depression and cardiovascular effects 1.
- The medication should be used with caution in patients with baseline respiratory insufficiency and/or cardiovascular instability, as it can exacerbate these conditions 1.
- Propofol infusion syndrome is a rare but potentially life-threatening condition that can occur with prolonged high-dose use, and its signs and symptoms include worsening metabolic acidosis, hypertriglyceridemia, hypotension, and arrhythmias 1.
From the FDA Drug Label
Propofol is an intravenous general anesthetic and sedation drug for use in the induction and maintenance of anesthesia or sedation. The mechanism of action, like all general anesthetics, is poorly understood However, propofol is thought to produce its sedative/anesthetic effects by the positive modulation of the inhibitory function of the neurotransmitter GABA through the ligand-gated GABAA receptors. Undesirable side effects, such as cardiorespiratory depression, are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in infusion rates. The hemodynamic effects of propofol injectable emulsion during induction of anesthesia vary. If spontaneous ventilation is maintained, the major cardiovascular effect is arterial hypotension (sometimes greater than a 30% decrease) with little or no change in heart rate and no appreciable decrease in cardiac output Induction of anesthesia with propofol injectable emulsion is frequently associated with apnea in both adults and pediatric patients.
Effects of Propofol:
- Cardiovascular effects: arterial hypotension, decreased cardiac output
- Respiratory effects: apnea, decrease in spontaneous minute ventilation, increase in carbon dioxide tension
- Neurological effects: sedation, anesthesia, positive modulation of GABA receptors
- Other effects: decrease in intraocular pressure, decrease in systemic vascular resistance
Key Considerations:
- Propofol should be titrated against the response of the patient until the clinical signs show the onset of anesthesia
- An adequate interval (3 minutes to 5 minutes) must be allowed between dose adjustments in order to assess clinical effects
- Rapid bolus doses should not be used, especially in elderly, debilitated, or ASA-PS III or IV patients, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation 2
- The concurrent administration of potent inhalational agents during maintenance with propofol injectable emulsion has not been extensively evaluated, but can be expected to increase the anesthetic or sedative and cardiorespiratory effects of propofol injectable emulsion 2
- The concomitant use of valproate and propofol may lead to increased blood levels of propofol, and the dose of propofol should be reduced when co-administering with valproate 2
From the Research
Overview of Propofol
- Propofol is a phenolic derivative with sedative and hypnotic properties, structurally unrelated to other sedative/hypnotic agents 3, 4.
- It has been used extensively as an anaesthetic agent, particularly in procedures of short duration, and has been investigated as a sedative in the intensive care unit (ICU) 3.
- Propofol provides sedation and hypnosis in a dose-dependent manner, with rapid onset and short duration of action 3, 4.
Clinical Efficacy
- Propofol has been shown to provide satisfactory sedation and good haemodynamic stability in mechanically ventilated patients in the ICU 3, 4.
- It has been compared to midazolam in several studies, with results showing that propofol provides similar or better sedation and faster recovery times 3, 4.
- Propofol has also been used in patients with head trauma, where it has been shown to reduce or maintain intracranial pressure 4.
Safety Profile
- Propofol has been associated with both antiarrhythmic and proarrhythmic effects, and can cause hypertriglyceridaemia with prolonged infusions 4, 5.
- Propofol infusion syndrome (PRIS) is a rare but serious complication that can occur with prolonged use of propofol 5.
- Strict aseptic technique must be used when handling propofol to prevent accidental extrinsic microbial contamination 4.
Comparison to Other Sedatives
- Propofol has been compared to fentanyl-midazolam combinations in several studies, with results showing that propofol provides better intubating conditions and faster recovery times 6, 7.
- Remifentanil-propofol combinations have been shown to be superior to fentanyl-midazolam combinations in terms of ventilation time and length of ICU stay 7.