Outcomes Research in Review

Nocturnal Dexmedetomidine for Prevention of Delirium in the ICU

Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-dose nocturnal dexmedetomidine prevents ICU delirium. A randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2018;197:1147-1156.



Study Overview

Objective. To determine if nocturnal dexmedetomidine prevents delirium and improves sleep in critically ill patients.

Design. Two-center, double-blind, placebo-controlled, randomized, trial.

Setting and participants. This study was conducted in the intensive care units (ICU) at 2 centers in North America between 2013 and 2016. Adults admitted to the ICU and receiving intermittent or continuous sedatives and expected to require at least 48 hours of ICU care were included in the study. Exclusion criteria were presence of delirium, severe dementia, acute neurologic injury, severe bradycardia, hepatic encephalopathy, end-stage liver disease, and expected death within 24 hours.

Intervention. Patients were randomized 1:1 to receive nocturnal dexmedetomidine (0.2–0.7 mcg/kg/hr) or dextrose 5% in water. Patients, clinicians, bedside nurses, and all study personnel were blinded to study drug assignment throughout the study. All sedatives were halved before the study drug was administered each evening. As-needed intravenous midazolam was used while titrating up the study drug. Study drug was administered nightly until either ICU discharge or an adverse event occurred. Decisions regarding use of other analgesic and sedative therapy, including opioids, oral benzodiazepines, acetaminophen, and nonsteroidal anti-inflammatory drugs, were left to the discretion of the clinician. Sleep-promoting agents such as melatonin or trazodone were not allowed.

Main outcome measures. The primary outcome was the proportion of patients who remained free of delirium during their critical illness. Secondary outcomes included ICU days spent without delirium; duration of delirium; sleep quality; proportion of patients who ever developed coma; proportion of nocturnal hours spent at each Richmond Agitation and Sedation Scale (RASS) score; maximal nocturnal pain levels; antipsychotic, corticosteroid, and oral analgesic use; days of mechanical ventilation; ICU and hospital stay duration; and ICU and hospital mortality.

Main results. 100 patients were randomized, with 50 patients in each group. 89% of patients were mechanically ventilated, and the Prediction of Delirium in ICU (PRE-DELIRIC) score [1] was 54 in the dexmedetomidine group and 51 in the placebo group. Continuous propofol and fentanyl infusion at randomization was used in 49% and 80%, respectively. Duration of median ICU stay was 10 days in the dexmedetomidine group and 9 days in the placebo group. More patients in the dexmedetomidine group (40 of 50 patients [80%]) than in the placebo group (27 of 50 patients [54%]) remained free of delirium (relative risk [RR], 0.44, 95% confidence interval {CI} 0.23 to 0.82; P = 0.006). The median (interquartile range [IQR]) duration of the first episode of delirium was similar between the dexmedetomidine (IQR 2.0 [0.6–2.7] days) and placebo (2.2 [0.7–3.2] days) groups (P = 0.73). The average Leeds Sleep Evaluation Questionnaire score also was similar (mean difference, 0.02, 95% CI 0.42 to 1.92) between the 2 groups. Incidence of hypotension or bradycardia did not differ significantly between the groups.

Conclusion. Nocturnal administration of low-dose dexmedetomidine in critically ill adults reduces the incidence of delirium during the ICU stay, and patient-reported sleep quality appears unchanged.

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