Reports of death with use of propofol (Diprivan) for nonprocedural (long-term) sedation and literature review.

PROPOFOL (Diprivan; AstraZeneca Pharmaceuticals, Wilmington, DE) has been marketed in the United States since November 1989. To date, there have been numerous case reports, case series, studies, and commentaries from researchers in various countries regarding adverse reactions and death in pediatric and adult patients to whom propofol was prescribed primarily for nonprocedural (long-term) sedation, although adverse events have been reported for anesthesia and procedural sedation as well. Many of the above have focused on “propofol infusion syndrome,” a cardiovascular and metabolic derangement that has been described in both pediatric and adult patients sedated with propofol. Sedation with propofol in children has been controversial because of these reports and since the announcement in 2001 of a trend toward statistical significance of a concentration-dependent increase in 28-day mortality in propofol-treated patients in a randomized controlled clinical trial of 327 pediatric patients. In this trial, the group who received standard sedation with lorazepam had 4% mortality, those treated with 1% propofol had 8% mortality, and those receiving 2% propofol (not approved in the United States) had 11% mortality despite a similarity in Pediatric Risk of Mortality scores for the three groups. These results led to a product labeling change that stated, “While causality has not been established, Diprivan injectable emulsion is not indicated for sedation in pediatric patients until further studies have been performed to document its safety in that population.” Nevertheless, propofol has been used for sedation in children and adults because it has a rapid onset and a short duration of action once discontinued, although a slightly longer recovery has been reported after more than 12 h of infusion. This article provides a review and analysis of US reports of death after pediatric and adult sedation with propofol that were submitted to the Food and Drug Administration (FDA) and entered into its postmarketing drug safety database. Published reports and studies are also included for comparison with the postmarketing reports.