Daily sedative interruption versus intermittent sedation in mechanically ventilated critically ill patients: a randomized trial

Abstract

Background: Daily sedative interruption and intermittent sedation are effective in abbreviating the time on mechanical ventilation. Whether one is superior to the other has not yet been determined. Our aim was to compare daily interruption and intermittent sedation during the mechanical ventilation period in a low nurse staffing ICU.

Methods: Adult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge.

Results: A total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P = 0.160). There were also no differences in ICU mortality (40 versus 23.3%, P = 0.165), hospital mortality (43.3 versus 30%, P = 0.284), incidence of delirium (30 versus 40%, P = 0.472), self-extubation (3.3 versus 6.7%, P = 0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not different between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P < 0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P < 0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay.

Conclusions: There was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses.

Trial registration: ClinicalTrials.gov Identifier: NCT00824239.

Keywords: Conscious sedation; Critical care and outcome assessment; Mechanical ventilation; Sedation.

Figure 1

Assessment and randomization.

Figure 2

Kaplan-Meier plot of length of mechanical ventilation.

Figure 3

Drug dosages of both groups up to the fifth day after mechanical ventilation initiation. Panel (A) shows the median dosage of fentanyl of all 60 patients (P < 0.001 for time interaction and P = 0.015 for group interaction); panel (B) shows the median dosage of midazolam of all 60 patients (P = 0.025 for time interaction and P = 0.002 for group interaction); panel (C) shows the median dosage of propofol of all 60 patients (P = 0.124 for time interaction and P = 0.549 for group interaction); panel (D) shows the median dosage of fentanyl of patients who used fentanyl in at least one day during the first five days after ICU admission (P = 0.729 for time interaction and P = 0.021 for group interaction); panel (E) shows the median dosage of midazolam of patients who used midazolam in at least one day during the first five days after ICU admission (P = 0.299 for time interaction and P = 0.169 for group interaction); and panel (F) shows the median dosage of propofol of patients who used propofol in at least one day during the first five days after ICU admission (P = 0.907 for time interaction and P = 0.641 for group interaction).

Figure 4

Physiologic variables of both groups up to the fifth day after mechanical ventilation initiation. Panels (A) (mixed model fixed effects P = 0.412 for time interaction and P = 0.202 for group interaction) and (D) (mixed model fixed effects P = 0.047 for time interaction and P = 0.608 for group interaction) show the maximal and minimal heart rate; panels (B) (mixed model fixed effects P < 0.001 for time interaction and P = 0.566 for group interaction) and (E) (mixed model fixed effects P < 0.001 for time interaction and P = 0.524 for group interaction) show the mean arterial blood pressure; and panels (C) (mixed model fixed effects P = 0.462 for time interaction and P = 0.801 for group interaction) and (F) (mixed model fixed effects P = 0.991 for time interaction and P = 0.259 for group interaction) show the respiratory rate.

Figure 5

Respiratory variables of both groups up to the fifth day after mechanical ventilation initiation. Panel (A) shows the peak pressure of all patients (P = 0.002 for time interaction and P = 0.549 for group interaction); panel (B) shows the driving pressure of all patients (P = 0.456 for time interaction and P = 0.549 for group interaction); panel (C) shows the median dosage of propofol of all patients (P = 0.001 for time interaction and P = 0.929 for group interaction); panel (D) shows the driving pressure of all patients (P = 0.549 for time interaction and P = 0.001 for group interaction); panel (E) shows the PaO₂/FiO₂ (P/F) ratio of the patients (P = 0.002 for time interaction and P = 0.793 for group interaction); and panel (F) shows the PaCO₂ of all patients (P = 0.151 for time interaction and P = 0.334 for group interaction). *P < 0.05 versus intermittent sedation group, Mann-Whitney post hoc test. #P < 0.05 versus first day of the same group, Mann-Whitney post hoc test.