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.

Validation of an automated surveillance approach for drain-related meningitis: a multicenter study.

OBJECTIVE Manual surveillance of healthcare-associated infections is cumbersome and vulnerable to subjective interpretation. Automated systems are under development to improve efficiency and reliability of surveillance, for example by selecting high-risk patients requiring manual chart review. In this study, we aimed to validate a previously developed multivariable prediction modeling approach for detecting drain-related meningitis (DRM) in neurosurgical patients and to assess its merits compared to conventional methods of automated surveillance. METHODS Prospective cohort study in 3 hospitals assessing the accuracy and efficiency of 2 automated surveillance methods for detecting DRM, the multivariable prediction model and a classification algorithm, using manual chart review as the reference standard. All 3 methods of surveillance were performed independently. Patients receiving cerebrospinal fluid drains were included (2012-2013), except children, and patients deceased within 24 hours or with pre-existing meningitis. Data required by automated surveillance methods were extracted from routine care clinical data warehouses. RESULTS In total, DRM occurred in 37 of 366 external cerebrospinal fluid drainage episodes (12.3/1000 drain days at risk). The multivariable prediction model had good discriminatory power (area under the ROC curve 0.91-1.00 by hospital), had adequate overall calibration, and could identify high-risk patients requiring manual confirmation with 97.3% sensitivity and 52.2% positive predictive value, decreasing the workload for manual surveillance by 81%. The multivariable approach was more efficient than classification algorithms in 2 of 3 hospitals. CONCLUSIONS Automated surveillance of DRM using a multivariable prediction model in multiple hospitals considerably reduced the burden for manual chart review at near-perfect sensitivity.

Extracerebral organ dysfunction in the acute stage after aneurysmal subarachnoid hemorrhage.

In patients with aneurysmal subarachnoid hemorrhage (SAH), secondary complications are an important cause of morbidity and case fatality. Delayed cerebral ischemia and hydrocephalus are important intracranial secondary complications. Potentially treatable extracranial complications are also frequently observed, and some are related to the occurrence of delayed cerebral ischemia and outcome. In addition to the occurrence of an inflammatory response and metabolic derangements, cardiac and pulmonary complications are the most common extracranial complications. This article provides an overview of the most common extracranial complications in patients with SAH and describes their effects on outcome and delayed cerebral ischemia.

The simplified acute physiology score to predict outcome in patients with subarachnoid hemorrhage.

OBJECTIVE: Current prognosticators for patients with subarachnoid hemorrhage (SAH) do not take into account signs of extracerebral organ dysfunction. This may explain the only moderate predictive value of these prognosticators. We assessed the prognostic value of the simplified acute physiology score (SAPS) II in SAH patients. METHODS: In a retrospective cohort study of 148 consecutive SAH patients, we related the SAPS II calculated within 24 hours after admission to clinical and initial computed tomographic imaging characteristics using the Mann-Whitney U test. We compared the prognostic value of the SAPS II with that of the World Federation of Neurosurgical Surgeons score, the patient's age, and the amount of blood showing in computed tomographic imaging for the occurrence of delayed cerebral ischemia using Cox proportional hazards modeling or, for poor outcome (death or dependence), logistic regression modeling. RESULTS: In the univariate analysis, the SAPS II was the strongest prognosticator; in the multivariate model, the SAPS II was the only independent predictor for outcome (odds ratio, 1.08; 95% confidence interval, 1.06-1.11]). Patients in the highest tertile of SAPS II had a significantly higher risk of poor outcome than those in the lowest tertile (odds ratio, 30.9; 95% confidence interval, 9.9-96.7]). The SAPS II was also the only independent predictor for the occurrence of delayed cerebral ischemia (hazard ratio, 1.020; 95% confidence interval, 1.002-1.039]). CONCLUSION: The SAPS II is a useful and reliable prognosticator in SAH patients. This score may provide more information than specific SAH scales in predicting poor outcome or the occurrence of delayed cerebral ischemia in some circumstances.