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May - 2018

   

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Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium

Y Skrobik, M Duprey, N Hill, J Devlin Am J Resp Crit Care Med, 2018, 197(9);1147-1156

Comment

The intersection between sleep, sedation, critical illness and delirium remains important and unsolved. Could dexmedetomidine, used as a nocturnal agent, improve sleep and reduce delirium?

This prospective phase II RCT;

  • Randomized 100 delirium-free critically ill adults receiving sedatives to receive nocturnal (9:30 p.m. to 6:15 a.m.) intravenous dexmedetomidine (0.2 μg/kg/h, titrated by 0.1 μg /kg/h every 15 min until a goal Richmond Agitation and Sedation Scale score of −1 or maximum rate of 0.7 μg/kg/h was reached) or placebo until ICU discharge. 
  • During study infusions, all sedatives were halved; opioids were unchanged. 
  • Delirium assessed using the Intensive Care Delirium Screening Checklist every 12 hours 
  • Sleep evaluated each morning by the Leeds Sleep Evaluation Questionnaire.
  • Baseline data similar, 62 yrs age, 72% medical, 40% receiving no sedation at enrolment, 90% ventilated, 2-days in ICU prior to enrolment
  • Average maximum dex rate was 0.5 ug/kg/hr, fewer dex patients received fentanyl infusions (94% vs 76%)and their propofol use was lower (22 vs 35 uk/kg/min)
  • Primary outcome: Nocturnal dexmedetomidine associated with greater proportion of patients who remained delirium-free during ICU 80% vs 54%, RR 0.44; 95% CI 0.23–0.82; P = 0.006
  • Dex group spent lower proportion of study days in coma (p=0.009), greater proportion of study days at rASS score of -1 or greater (55% vs 24%, p<0.0001).
  • Pain similar during nocturnal period
  • Leeds Sleep Evaluation Questionnaire score not different  
  • Incidence of hypotension, bradycardia, or both did not differ 

 

In conclusion nocturnal administration of low-dose dexmedetomidine in critically ill adults was associated with less ICU delirium, days spent with coma, and opiate requirements. Sleep and adverse events did not differ.


 

Abstract

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 (9:30 p.m. to 6:15 a.m.) intravenous dexmedetomidine (0.2 μg/kg/h, titrated by 0.1 μg /kg/h every 15 min until a goal Richmond Agitation and Sedation Scale score of −1 or maximum rate of 0.7 μg/kg/h 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.

Measurements and Main Results: Nocturnal dexmedetomidine (vs. 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]; relative risk, 0.44; 95% confidence interval, 0.23–0.82; P = 0.006). The average Leeds Sleep Evaluation Questionnaire score was similar (mean difference, 0.02; 95% confidence interval, 0.42–1.92) between the 34 dexmedetomidine (average seven assessments per patient) and 30 placebo (six per patient) group patients able to provide one or more assessments. 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.

 

May


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