Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study

TLDR

Propofol can cause a potentially fatal infusion syndrome (PRIS), but its incidence remains unknown. This prospective multicenter study seeks to quantify the incidence and clinical manifestations of PRIS in critically ill adults to guide future comparative sedative trials. The investigators monitored 1,017 patients from 11 academic centers who received propofol for ≥24 h, recording daily the presence of 11 PRIS‑associated signs and risk factors derived from 83 published case reports. PRIS occurred in 1.1 % of patients (11/1,017), typically after 3 days, with higher APACHE II scores but similar propofol duration and ICU stay, indicating an incidence slightly above 1 % despite a conservative definition.

Abstract

Abstract Introduction While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol. Methods Critically ill adults from 11 academic medical centers administered an infusion of propofol for [>/=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS. Results Among 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>/=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use ( P = 0.43) and ICU length of stay ( P = 0.82) were similar. Conclusions Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.