Propofol vs midazolam for sedation in acutely ill mechanically ventilated children (PROPOSE): A randomized controlled trial

Acutely ill children aged 1 – 12 years mechanically ventilated in PICU and expected to remain ventilated for at least 12 hours will be randomized to receive either propofol infusion (1 to 4 mg/kg/hr) or midazolam infusion (2 to 4 mcg/kg/min) for sedation. Level of sedation will be assessed using the Richmond Agitation Sedation Scale (RASS). Target RASS score for the day will be determined before starting the study drug and every morning at daily sedation holidays. RASS score will be assessed every 30 minutes till the target RASS is reached and then every 2 hourly or more frequently if needed. Infusion of the study drug will be continued till a maximum of three days or until sedation was no longer required, whichever occurs earlier. Sedation holidays will be given daily for 2 hours (8 am to 10 am) in all children, unless contraindicated. Fentanyl infusion at 2 to 4 mcg/kg/hr will be used for analgesia in both groups. All other treatment modalities including ventilation management and weaning, cardiovascular support and monitoring, etc will be similar in both groups, as per standard unit protocols. The primary outcome of the study is the percentage of time spent in the targeted sedation level in the first 72 hours after randomization. The secondary outcomes are need for top-up doses of midazolam, propofol, fentanyl, and vecuronium, 28 day ventilator free days, length of PICU and hospital stay, 28 day mortality, treatment failure rate, incidence of extubation failure, incidence of adverse events related to sedation, and incidence of occurrence of iatrogenic withdrawal syndrome and ICU delirium. Patients will be followed up till 28 days after randomization or death whichever is earlier.