A low dose of the sedative dexmedetomidine given at night may prevent delirium in critically ill ICU patients, according to research. Researchers report on what is believed to be the first investigation to identify a drug to prevent adults from developing delirium in the ICU.
The study was led by Dr Yoanna Skrobik, a clinician-scientist at McGill University Health Centre in Canada who conducted the first studies of delirium in the critically ill and whose research has shown that delirium prolongs hospital stay and increases mortality. "In other studies, dexmedetomidine has been associated with lower delirium prevalence rates than other sedatives," Skrobik said. "But whether dexmedetomidine might actually prevent delirium was not clear."
The study enrolled 100 ICU patients at two hospitals, one in Quebec, the other in Boston. The patients did not have delirium at the time of ICU enrolment. Half the patients were randomly assigned to receive intravenous dexmedetomidine; the other half were infused with the placebo. Neither the patients nor the ICU health care team knew which arm of the trial the patients were in.
The study found that compared to the placebo arm, those receiving dexmedetomidine during their ICU stay: were more likely to remain free of delirium throughout their ICU stay: 80% vs 54%; spent more days free of delirium in the ICU: 8 vs 6 days; and were less likely, if in pain, to experience severe pain: 44% vs 66%.
The authors expected that dexmedetomidine would also improve sleep quality. A previous study of a select group of critically ill patients found that to be the case. In the current study, however, there was no difference in sleep quality between the two groups, as assessed by a self-reported questionnaire.
Skrobik said that the sleep findings should be interpreted in light of two caveats: sleep in the ICU is almost always abnormal, and no validated instrument exists to identify when an ICU patient is experiencing normal vs abnormal sleep.
There was also no difference in length of ICU stay or hospital stay, or in ICU mortality. However, a reduction in opiate requirements confirmed other studies describing dexmedetomidine's potential to relieve pain.
"We believe this is a practice-altering study and that dexmedetomidine should be used with patients at high risk for delirium," Skrobik said.
Rationale: Dexmedetomidine is associated with less delirium than benzodiazepines, and better sleep architecture than either benzodiazepines or propofol; its effect on delirium and sleep when administered at night to patients requiring sedation remains unclear. Objectives: To determine if nocturnal dexmedetomidine prevents delirium and improves sleep in critically ill adults. Methods: This two-center, double-blind, placebo-controlled trial randomized 100 delirium-free critically ill adults receiving sedatives to receive nocturnal (21:30 to 6:15h) intravenous dexmedetomidine (0.2 mcg/kg/min, titrated by 0.1 mcg/kg/min every 15 minutes until a goal RASS = -1 or maximum rate of 0.7 mcg/kg/min was reached) or placebo until ICU discharge. During study infusions, all sedatives were halved; opioids were unchanged. Delirium was assessed using the Intensive Care Delirium Screening Checklist every 12 hours throughout the ICU admission. Sleep was evaluated each morning by the Leeds Sleep Evaluation Questionnaire (LSEQ). Measurements and Main Results: Nocturnal dexmedetomidine (versus placebo) was associated with a greater proportion of patients who remained delirium-free during the ICU stay [dexmedetomidine [40 (80%) of 50 patients] vs. placebo [27 (54%) of 50 patients] (RR = 0.44, 95% CI, 0.23 to 0.82, p=0.006). The average LSEQ score was similar [MD 0.02; 95% CI, 0.42 to 1.92] between the 34 dexmedetomidine (average 7 assessments/patient) and 30 placebo (6/patient) group patients able to provide ≥ 1 assessment. Incidence of hypotension, bradycardia or both did not differ significantly between groups. Conclusions: Nocturnal administration of low-dose dexmedetomidine in critically ill adults reduces the incidence of delirium during the ICU stay; patient-reported sleep quality appears unchanged. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01791296.
Yoanna Skrobik, Matthew S Duprey, Nicholas S Hill, John W Devlin