Randomized trial comparing daily interruption of sedation and nursing-implemented sedation algorithm in medical intensive care unit patients

Abstract

Introduction: Daily interruption of sedation (DIS) and sedation algorithms (SAs) have been shown to decrease mechanical ventilation (MV) duration. We conducted a randomized study comparing these strategies.

Methods: Mechanically ventilated adults 18 years old or older in the medical intensive care unit (ICU) were randomly assigned to DIS or SA. Exclusion criteria were severe neurocognitive dysfunction, administration of neuromuscular blockers, and tracheostomy. Study endpoints were total MV duration and 28-day ventilator-free survival.

Results: The study was terminated prematurely after 74 patients were enrolled (DIS 36 and SA 38). The two groups had similar age, gender, racial distribution, Acute Physiology and Chronic Health Evaluation II score, and reason for MV. The Data Safety Monitoring Board convened after DIS patients were found to have higher hospital mortality; however, no causal connection between DIS and increased mortality was identified. Interim analysis demonstrated a significant difference in primary endpoint, and study termination was recommended. The DIS group had longer total duration of MV (median 6.7 versus 3.9 days; P = 0.0003), slower improvement of Sequential Organ Failure Assessment over time (0.70 versus 0.23 units per day; P = 0.025), longer ICU length of stay (15 versus 8 days; P < 0.0001), and longer hospital length of stay (23 versus 12 days; P = 0.01).

Conclusion: In our cohort of patients, the use of SA was associated with reduced duration of MV and lengths of stay compared with DIS. Based on these results, DIS may not be appropriate in all mechanically ventilated patients.

Trial registration: ClinicalTrials.gov NCT00205517.

Figure 1

The sedation algorithm used in this study. gtt, drop; MRICU, medical respiratory intensive care unit; prn, as necessary (pro re nata); q, every; qd, each day (quaque die); RASS, Richmond Agitation-Sedation Scale.

Figure 2

Kaplan-Meier survival curve of total duration of mechanical ventilation (MV) for patients treated by daily interruption of sedation (thick line) and sedation algorithm (thin line) (P = 0.0003).

Figure 3

Mixed-model repeated measures comparison of Richmond Agitation-Sedation Scale (RASS) score over the course of mechanical ventilation in patients treated by daily interruption of sedation (solid line) and sedation algorithm (dashed line). The group treated by daily interruption of sedation had higher RASS scores (P = 0.049). Individual measurements are shown (× for sedation algorithm and ▪ for daily interruption of sedation).

Figure 4

Sequential Organ Failure Assessment (SOFA) over time for the group of patients treated by daily interruption of sedation and sedation algorithm. The individual scores are represented for each group (▪ for daily interruption of sedation and × for sedation algorithm); the lines represent the composite SOFA for each group (thick line for daily interruption of sedation; dashed line for sedation algorithm). The SOFA improved more rapidly for the sedation algorithm group (P = 0.025). MV, mechanical ventilation.