Reade 2009.

Methods	RCT comparing haloperidol vs dexmedetomidine in facilitating extubation for patients with severe agitation Study took place in a single 20‐bed ICU (mixed medical and surgical) at a university hospital in Australia
Participants	Participants included 20 (N = 10 haloperidol, median age 68.5 (IQR 43 to 78) years, 80% male; N = 10 dexmedetomidine, median age 52 (IQR 42 to 69) years, 90% male) mechanically ventilated, critically ill patients who could not be extubated because their level of agitation (e.g. RASS score ≥ 2) required such a high dose of sedative drug (40% haloperidol group delirious at enrolment, 30% dexmedetomidine, using ICDSC ≥ 4; 100% haloperidol group at least subsyndromal delirium at enrolment, 80% dexmedetomidine, using ICDSC ≥ 0) Study enrolment between April 2006 and August 2008
Interventions	Participants received dexmedetomidine, started as an intravenous infusion of 0.2 to 0.7 mcg/kg/h (option of providing a loading dose of 1.0 μg/kg IV over a 20‐minute period), or haloperidol, started as an intravenous infusion of 0.5 to 2.0 mg/h (option of providing a loading dose of 2.5 mg). Nurses adjusted infusion rates as necessary (re‐assessing at least every 4 hours), with the aim of minimizing psychomotor agitation and achieving a RASS score of 0. Treatment was continued for as long as was deemed necessary by the treating physician, including following extubation. There was no strict protocol outlining the titration of either drug. Dexmedetomidine was not available in the hospital's formulary; once it was stopped, it could not be restarted. Haloperidol could however be administered for as long as needed The bedside nurse was responsible for transitioning the patient from mechanical to spontaneous ventilation as early as possible and through assessments done every 4 hours
Outcomes	Primary Time from start of study drug to extubation Secondary efficacy outcomes Time from start of study drug to ICU discharge Time to attain satisfactory sedation score Need for additional sedative and analgesic drugs Secondary safety outcomes Change in QTc interval Duration and rate of vasopressor or inotropic support Re‐intubation
Notes	Funding was provided by Australian College of Critical Care Nurses Australian and New Zealand College of Anaesthetists Dexmedetomidine was supplied free of charge by the manufacturer, Hospira, which had no other involvement in the study Registration Study was registered at clinicaltrials.gov under NCT00505804 Study authors were contracted and clarifications were provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A computer‐generated random‐number sequence was used. Numbered envelopes contained a card indicating allocation
Allocation concealment (selection bias)	Low risk	Participants were allocated via numbered envelopes into which a card indicating patient allocation had been placed according to a computer‐generated random numbers sequence
Blinding of participants and personnel (performance bias) All outcomes	High risk	The study used an open‐label study design. Clinical personnel were not blinded to the study drug
Blinding of outcome assessment (detection bias) All outcomes	High risk	The study used an open‐label study design and was not blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomized participants were included in the analysis. No eligible participants' relatives refused consent, and no patients were lost to follow‐up. 1 participant in the haloperidol group stopped the drug at physician request
Selective reporting (reporting bias)	Low risk	All outcomes reported in methods were included in results. Data presented for all participants were included in the analysis
Other bias	Low risk	Dexmedetomidine was supplied free of charge by the manufacturer, Hospira, which had no other involvement in the study