Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium: The REDUCE Randomized Clinical Trial.

Importance: Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium. Objective: To determine whether prophylactic use of haloperidol improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017. Interventions: Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride. Main Outcome and Measures: The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. Results: All 1789 randomized patients (mean, age 66.6 years [SD, 12.6]; 1099 men [61.4%]) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, -3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference, 0 days, 95% CI, 0-0 days for all 3 measures). The number of reported adverse effects did not differ between groups (2 [0.3%] for the 2-mg haloperidol group vs 1 [0.1%] for the placebo group). Conclusions and Relevance: Among critically ill adults at high risk of delirium, the use of prophylactic haloperidol compared with placebo did not improve survival at 28 days. These findings do not support the use of prophylactic haloperidol for reducing mortality in critically ill adults. Trial Registration: clinicaltrials.gov Identifier: NCT01785290.

Lung transplantation for ventilator-dependent respiratory failure.

INTRODUCTION: Lung transplantation of patients on mechanical ventilation is controversial, but successful transplantation of these patients has been reported. This report describes our institutional experience with lung transplantation of mechanically ventilated patients since 2003. METHODS: A retrospective cohort study was performed of all adult patients who underwent transplantation between October 2003 and October 2007. The patients on mechanical ventilation before transplantation were compared with patients without mechanical ventilation before transplantation. Survival, intensive care unit and hospital length of stay, post-transplant mechanical ventilation days, and primary graft function were analyzed. RESULTS: Before transplantation, 15 patients received mechanical ventilation for a median of 20 days (range, 5-90 days); of these, 13 underwent transplantation, and 2 died waiting for transplantation. The control group comprised 70 patients. Time on the transplantation waiting list was significantly shorter for the study group vs the control group. The 2 groups did not differ in survival, post-transplantation hospital time, and primary graft dysfunction scores at 0, 24, 48 and 72 hours after transplantation. Median time of mechanical ventilation after transplantation and median length of stay in the intensive care unit stay were longer in the study group. CONCLUSION: The survival rate and post-operative clinical course of patients undergoing transplantation while receiving mechanical ventilation for respiratory failure suggest that these patients can be considered for lung transplantation. Despite a longer time on post-operative mechanical ventilation and length of ICU stay, outcome is similar to that of other lung transplant candidates.