Context  Protocolized sedation and daily sedative interruption are 2 strategies to minimize sedation and reduce the duration of mechanical ventilation and intensive care unit (ICU) stay. We hypothesized that combining these strategies would augment the benefits.
Objective  To compare protocolized sedation with protocolized sedation plus daily sedation interruption in critically ill patients.
Design, Setting, and Patients  Randomized controlled trial of 430 critically ill, mechanically ventilated adults conducted in 16 tertiary care medical and surgical ICUs in Canada and the United States between January 2008 and July 2011.
Intervention  Continuous opioid and/or benzodiazepine infusions and random allocation to protocolized sedation (n = 209) (control) or to protocolized sedation plus daily sedation interruption (n = 214). Using validated scales, nurses titrated infusions to achieve light sedation. For patients receiving daily interruption, nurses resumed infusions, if indicated, at half of previous doses. Patients were assessed for delirium and for readiness for unassisted breathing.
Main Outcome Measure  Time to successful extubation. Secondary outcomes included duration of stay, doses of sedatives and analgesics, unintentional device removal, delirium, and nurse and respiratory therapist clinical workload (on a 10-point visual analog scale [VAS]).
Results  Median time to successful extubation was 7 days in both the interruption and control groups (median [IQR], 7 [4-13] vs 7 [3-12]; interruption group hazard ratio, 1.08; 95% CI, 0.86-1.35; P = .52). Duration of ICU stay (median [IQR], 10 [5-17] vs 10 [6-20]; P = .36) and hospital stay (median [IQR], 20 [10-36] vs 20 [10-48]; P = .42) did not differ between the daily interruption and control groups, respectively. Daily interruption was associated with higher mean daily doses of midazolam (102 mg/d vs 82 mg/d; P = .04) and fentanyl (median [IQR], 550 [50-1850] vs 260 [0-1400]; P < .001) and more daily boluses of benzodiazepines (mean, 0.253 vs 0.177; P = .007) and opiates (mean, 2.18 vs 1.79; P < .001). Unintentional endotracheal tube removal occurred in 10 of 214 (4.7%) vs 12 of 207 patients (5.8%) in the interruption and control groups, respectively (relative risk, 0.82; 95% CI, 0.36-1.84; P = .64). Rates of delirium were not significantly different between groups (53.3% vs 54.1%; relative risk, 0.98; 95% CI, 0.82-1.17; P = .83). Nurse workload was greater in the interruption group (VAS score, 4.22 vs 3.80; mean difference, 0.41; 95% CI, 0.17-0.66; P = .001).
Conclusion  For mechanically ventilated adults managed with protocolized sedation, the addition of daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay.
Trial Registration  clinicaltrials.gov Identifier: NCT00675363