Propofol. An overview of its pharmacology and a review of its clinical efficacy in intensive care sedation

Abstract

Propofol is a phenolic derivative that is structurally unrelated to other sedative hypnotic agents. It has been used extensively as an anaesthetic agent, particularly in procedures of short duration. More recently it has been investigated as a sedative in the intensive care unit (ICU) where it produces sedation and hypnosis in a dose-dependent manner. Propofol also provides control of stress responses and has anticonvulsant and amnesic properties. Importantly, its pharmacokinetic properties are characterised by a rapid onset and short duration of action. Noncomparative and comparative trials have evaluated the use of propofol for the sedation of mechanically ventilated patients in the ICU (postsurgical, general medical, trauma). Overall, propofol provides satisfactory sedation and is associated with good haemodynamic stability. It produces results similar to or better than those seen with midazolam or other comparator agents when the quality of sedation and/or the amount of time that patients were at adequate levels of sedation are measured. Patients sedated with propofol also tend to have a faster recovery (time to spontaneous ventilation or extubation) than patients sedated with midazolam. Although most studies did not measure time to discharge from the ICU, propofol tended to be superior to midazolam in this respect. In a few small trials in patients with head trauma or following neurosurgery, propofol was associated with adequate sedation and control of cerebral haemodynamics. The rapid recovery of patients after stopping propofol makes it an attractive option in the ICU, particularly for patients requiring only short term sedation. In short term sedation, propofol, despite its generally higher acquisition costs, has the potential to reduce overall medical costs if patients are able to be extubated and discharged from the ICU sooner. Because of the potential for hyperlipidaemia and the development of tolerance to its sedative effects, and because of the reduced need for rapid reversal of drug effects in long term sedation, the usefulness of propofol in long term situations is less well established. While experience with propofol for the sedation of patients in the ICU is extensive, there are still areas requiring further investigation. These include studies in children, trials examining cerebral and haemodynamic outcomes following long term administration and in patients with head trauma and, importantly, pharmacoeconomic investigations to determine those situations where propofol is cost effective. In the meantime, propofol is a well established treatment native to benzodiazepines and/or other hypnotics or analgesics when sedation of patients in the ICU is required. In particular, propofol possesses unique advantages over these agents in patients requiring only short term sedation.