PROPOFOL - AN OVERVIEW OF ITS PHARMACOLOGY AND A REVIEW OF ITS CLINICAL EFFICACY IN INTENSIVE-CARE SEDATION

Propofol is a phenolic derivative that is structurally unrelated to ot her sedative hypnotic agents. It has been used extensively as an anaes thetic agent, particularly in procedures of short duration. More recen tly it has been investigated as a sedative in the intensive care unit (ICU) where it produces sedation and hypnosis in a dose-dependent mann er: Propofol also provides control of stress responses and has anticon vulsant and amnesic properties. Importantly, its pharmacokinetic prope rties are characterised by a rapid onset and short duration of action. Noncomparative and comparative trials have evaluated the use of propo fol for the sedation of mechanically ventilated patients in the ICU (p ostsurgical, general medical, trauma). Overall, propofol provides sati sfactory sedation and is associated with good haemodynamic stability. It produces results similar to or better than those seen with midazola m or other comparator agents when the quality of sedation and/or the a mount of time that patients were at adequate levels of sedation are me asured. Patients sedated with propofol also tend to have a faster reco very (time to spontaneous ventilation or extubation) than patients sed ated with midazolam. Although most studies did not measure time to dis charge from the ICU, propofol tended to be superior to midazolam in th is respect. In a few small trials in patients with head trauma or foll owing neurosurgery, propofol was associated with adequate sedation and control of cerebral haemodynamics. The rapid recovery of patients aft er stopping propofol makes it an attractive option in the ICU, particu larly for patients requiring only short term sedation. In short term s edation, 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 poten tial for hyperlipidaemia and the development of tolerance to its sedat ive effects, and because of the reduced need for rapid reversal of dru g effects in long term sedation, the usefulness of propofol in long te rm 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 child ren, trials examining cerebral and haemodynamic outcomes following lon g term administration and in patients with head trauma and, importantl y, pharmacoeconomic investigations to determine those situations where propofol is cost effective. In the meantime, propofol is a well estab lished treatment alternative to benzodiazepines and/or other hypnotics or analgesics when sedation of patients in the ICU is required. In pa rticular, propofol possesses unique advantages over these agents in pa tients requiring only short term sedation.