Russel J Roberts

Introduction: We hypothesized that delirium symptoms may respond differently to antipsychotic therapy. The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the database of a randomized, double-blind, placebo-controlled study comparing quetiapine (Q) or placebo (P), both with haloperidol rescue, for critically ill patients with delirium. Methods: Data for 10 delirium symptoms from the eight-domain, intensive care delirium screening checklist (ICDSC) previously collected every 12 hours were extracted for 29 study patients. Data between the Q and P groups were compared using a cut-off P- value of ≤0.10 for this exploratory study. Results: Baseline ICDSC scores (5 (4 to 7) (Q) vs 5 (4 to 6)) (median, interquartile range (IQR)) and % of patients with each ICDSC symptom were similar in the two groups (all P > 0.10). Among patients with the delirium symptom at baseline, use of Q may lead to a shorter time (days) to first resolution of symptom fluctuation (4 (Q) vs. 14, P = 0.004), inattention (3 vs. 8, P = .10) and disorientation (2 vs. 10, P = 0.10) but a longer time to first resolution of agitation (3 vs. 1, P = 0.04) and hyperactivity (5 vs. 1, P = 0.07). Among all patients, Q-treated patients tended to spend a smaller percent of time with inattention (47 (0 to 67) vs. 78 (43 to 100), P = 0.025), hallucinations (0 (0 to 17) vs. 28 (0 to 43), P = 0.10) and symptom fluctuation (47 (19 to 67) vs. 89 (33 to 00), P = 0.04] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness (26% (13 to 63%) vs. 14% (0 to 33%), P = 0.17]. Conclusions: Our exploratory analysis suggests that quetiapine may resolve several intensive care unit (ICU) delirium symptoms faster than the placebo. Individual symptom resolution appears to differ in association with the pharmacologic intervention (that is, P vs Q, both with as needed haloperidol). Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes.

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.