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

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 [>or=] 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 [>or=] 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.

Figure 1

Timing of each PRIS-defining clinical manifestation relative to the start of propofol therapy initiation and admission APACHE II score among the 11 patients who developed PRIS. APACHE = acute physiology and chronic health evaluation; PRIS = propofol-relation infusion syndrome.

Figure 2

PRIS clinical manifestations. (a) Frequency of PRIS clinical manifestations and risk factors among all patients receiving propofol (n = 1017). (b) Frequency of specific cardiac and renal PRIS clinical manifestations among all patients receiving propofol (n = 1017). PRIS = propofol-relation infusion syndrome.

Figure 3

Total number of new-onset PRIS clinical manifestations among all patients receiving propofol (n = 1017). PRIS = propofol-relation infusion syndrome.

Figure 4

Cumulative average number of new-onset PRIS clinical manifestations per patient by the day of propofol therapy received among all patients receiving propofol (n = 1017). PRIS = propofol-relation infusion syndrome.