Propofol in patients needing long-term sedation in intensive care: an assessment of the development of tolerance - A pilot study

Objective: To evaluate the possible development of tolerance in patients sedated with propofol in intensive care for more than 5 days. Design: An open within patient noncomparative pilot study. Setting: The intensive care unit of a hospital in the UK. Patients: Twenty-three patients who were expected to need sedation with propofol for more than 5 days were included; of these, 11 were sedated continuously for between 5 and 10 days. Interventions: Propofol was infused continuously at about 0.5-4 mg/kg per h to provide sedation at level 3 on the Ramsay scale (drowsy or asleep, responds easily to commands). Alfentanil was infused at a rate of about 0.5 mu g/kg per min. Measurements and results: Patients with a statistically significant increase in both infusion rate and blood concentration were considered to show tolerance, those that required an increasing infusion rate and constant (or decreasing) blood concentration were said to show increased clearance, and those that required constant (or decreasing) infusion rates and blood concentrations were classed as showing no tolerance. Of the 11 patients who were sedated for more than 5 days, three showed tolerance and three showed increased clearance while five showed no tolerance. The desired sedation level was achieved for the majority of the time for patients sedated between 5 and 10 days (mean 73-90 %). There was some suggestion of a relationship between improving health (decreasing APACHE II scores) and the need for increased infusions of propofol. Conclusions: Although there were insufficient data to reach firm conclusions, the possibility of some relationship between the increasing need for propofol and improving condition in patients needing longer term intensive care cannot be ruled out.