One of the major goals in caring for critically ill patients is to liberate them from mechanical ventilation. Sedatives used to facilitate mechanical ventilation are often short-acting, but can accumulate with prolonged use, renal and/or hepatic dysfunction.1 Daily interruption of sedatives and nursing-implemented sedation titration protocols are two strategies to minimize excessive sedation and reduce the duration of mechanical ventilation and intensive care unit (ICU) stay.2,3 However, use of these strategies in clinical practice have been inconsistent.4,5 The objective of the SLEAP study was to determine the impact of combining both strategies on the duration of mechanical ventilation.
Across 16 medical and surgical ICUs in Canada and the United States, 430 critically ill, mechanically ventilated adults were randomized to either daily sedation interruption plus protocolized sedation or protocolized sedation alone. Nurses used a standardized protocol to titrate continuous infusions of opioids (morphine, fentanyl, or hydromorphone) and/or benzodiazepines (midazolam, or lorazepam) to achieve a target Sedation-Agitation Scale (SAS) score of 3 or 4 or Richmond Agitation Sedation Scale (RASS) score of -3 to 0. Sedation needs were assessed hourly. In the intervention group, the bedside nurse interrupted benzodiazepine and opioid infusions daily and assessed for wakefulness (SAS 4 to 7 or RASS -1 to 4) and the ability to follow commands. If needed, the infusions were resumed at half the previous dose and titrated as per protocol. Patients in both arms were evaluated daily by respiratory therapists on readiness for unassisted breathing. If a spontaneous breathing trial was passed, the treating physician made the decision whether to extubate.
The median time to successful extubation was 7 days in both groups (median[IQR] 7[4-13] vs. 7[3-12]; hazard ratio 1.08 (95% CI 0.86-1.3); p=0.52). There was no significant difference between groups in ICU or hospital lengths of stay, hospital mortality, rates of unintentional device removal, delirium, or ICU neuroimaging. Patients in the daily interruption group received higher mean daily doses of benzodiazepines (102 vs. 82 mg/d midazolam equivalents; p=0.04) and opioids (1780 vs. 1070 mcg/d fentanyl equivalents; p<0.001). Mean sedation scores achieved per patient were similar in the 2 groups, but nursing workload was significantly higher in the interruption group (mean VAS score 4.22 vs. 3.80; mean difference 0.41 (95% CI 0.17-0.66); p=0.001). No significant difference in respiratory therapist workload was reported.
These unexpected findings may be due to a number of factors. First, the nurse-implemented sedation protocol targeted a lighter level of sedation compared to previous trials.3,6 The benefit of daily sedative interruption to minimize sedation may therefore depend on the baseline usual care. Second, surveys have found reluctance to interrupt sedative infusions due to concerns for patient discomfort, respiratory distress and safety.7 The open-label design of the trial may have allowed reservations from the ICU staff to influence results.
In conclusion, critically ill patients receiving mechanical ventilation and nurse-implemented sedation protocol targeting light sedation, the addition of daily sedative interruption did not reduce the duration of mechanical ventilation, and may increase sedative and analgesic use and nurse workload.
While the addition of daily interruption did not reduce the duration of mechanical ventilation, it should be noted that the protocol that was utilized in this study is adjusted on an ...