Randomized controlled trial of interrupted versus continuous sedative infusions in ventilated children.

OBJECTIVE: To compare daily interruption vs. continuous sedative infusions in mechanically ventilated children with respect to lengths of mechanical ventilation and intensive care unit stay.
DESIGN: Prospective randomized controlled trial.
SETTING: Pediatric intensive care unit of a tertiary care teaching and referral hospital. PATIENTS: One hundred two patients mechanically ventilated for >48 hrs.
INTERVENTIONS: Patients were randomized to receive either continuous (group 1) or interrupted (group 2) sedative infusion (midazolam bolus of 0.1 mg/kg, followed by infusion, to achieve a Ramsay score of 3-4). Each patient in group 2 had daily interruption of infusion at 8:00 AM till he/she became fully awake (response to verbal commands) or so agitated/uncomfortable that he/she needed restarting of infusion (whichever was earlier) at a dose 50% less than the previous dose. Primary outcome variables were the lengths of mechanical ventilation and intensive care unit stay, while the number and percentage of days awake on sedative infusions, frequency of adverse events, and total dose of sedatives required were the secondary outcome variables.
MEASUREMENTS AND MAIN RESULTS: Of the 102 patients included in the study, 56 were randomized into the continuous sedation protocol and 46 into the interrupted sedation protocol. Both were statistically similar with respect to demography, primary diagnosis, severity of illness score (Pediatric Risk of Mortality I and III), indication for mechanical ventilation, and initial ventilatory variables except that the patients under the interrupted arm had lower peak inspiratory pressure and positive end-expiratory pressure requirements at the start of ventilation (p = .002 and p = .028, respectively). The mean (SD) length of mechanical ventilation in the interrupted sedation protocol was significantly less than that in the continuous sedation protocol (7.0 ± 4.8 days vs. 10.3 ± 8.4 days; p = .021). Similarly, the difference in the median duration of pediatric intensive care unit stay was significantly less in the interrupted sedation as compared to the continuous sedation protocol (10.7 days vs. 14.0 days; p = .048). The mean total dose of midazolam and the total calculated cost of midazolam in the former were significantly less compared to those of the latter (7.1 ± 4.7 mL vs. 10.9 ± 6.9 mL, p = .002; 4827 ± 5445 rupees vs. 13,865 ± 25,338 rupees, p = .020). The frequencies of adverse events in both the groups were however similar.
CONCLUSION: The length of mechanical ventilation, duration of intensive care unit stay, total dose of midazolam, and average calculated cost of the therapy were significantly reduced in the interrupted as compared to the continuous group of sedation.

RCT Entities:   Population Interventions Outcomes