Nassar 2014.

Methods	Single‐centre, randomized controlled trial. Setting: low nurse staffing ICU (developing country) with 6 beds, an academic tertiary hospital Country: Brazil Groups: intermittent sedation vs. daily interruption Period: January 2009 to December 2011
Participants	Sample size: 60 (30/30) Included Patients requiring mechanical ventilation within the last 24 hours and expected to need mechanical ventilation for more than 24 hours Excluded Patients younger < 18 years Pregnant women Needing deep levels of sedation (intracranial hypertension, status epilepticus, hypothermia after cardiac arrest, severe asthma exacerbations, and severe hypoxaemic respiratory failure (PaO₂/FiO₂ ratio < 50) Not expected to survive for more than 6 months Previous cognitive impairment (for example, advanced dementia) Previous participation in the trial Missing: not reported, all patients accounted for in flowchart.
Interventions	Intervention: daily interruption of continuous sedative and opioid infusion. This group received midazolam/propofol at the discretion of the attending physician to reach the sedation goal which was having the patient awake or easily aroused with gentle stimulus. Every morning at 7.00 am the sedation was stopped. If the patient was agitated or could not follow commands, the infusion was restarted at half dose. Control: intermittent sedation. The intermittent sedation group would be kept without continuous infusion of sedatives. Agitation and pain were treated and delirium was treated with haloperidol. If the patient was still uncomfortable midazolam/propofol infusion was started and interruption of the sedation would be attempted in the next shift In both groups. The goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4 (calm, easily aroused or awakened with verbal stimuli). Midazolam or propofol was used at the discretion of the attending physician.
Outcomes	Primary Ventilator‐free days in 28 days Secondary ICU mortality Hospital mortality Incidence of delirium Delirium‐ and coma‐free days in 7 days Nurse workload Self‐extubation Psychological distress 6 months after ICU discharge Delirium measured by: CAM‐ICU Adverse events: self‐extubations (2/1), accidental removal of catheters (1/2)
Notes	Conclusion: there were no differences in ventilator‐free days within 28 days between daily interruption and intermittent sedation; and no difference in the incidence of delirium. Authors calculated that a sample size of 106 patients would be required to detect a mean difference of 2 days of mechanical ventilation. The trial was stopped prematurely due to slow inclusion. The 2 interventions are very similar. Funding: not stated Conflict of interest: the authors declare that they have no competing interests Study number: NCT00824239. Contact with authors: none
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random selection of opaque sealed envelopes from a box with 120 envelopes
Allocation concealment (selection bias)	Low risk	Concealed by random selection of opaque sealed envelopes
Incomplete outcome data (attrition bias) All outcomes	Low risk	Groups were well balanced
Selective reporting (reporting bias)	Low risk	All outcomes in the online protocol (NCT00824239) were reported
Other bias	High risk	The trial was not sufficiently powered to show 1 intervention superior to the other
Blinding of participants and personnel (performance bias) All outcomes	High risk	Attending clinicians were aware of which group the included patients were allocated to
Blinding of outcome assessment (detection bias) All outcomes	High risk	Research staff were aware of which group the included patients were allocated to.