Schweickert 2009.

Methods	Parallel‐group RCT
Participants	104 sedated medical ICU patients ≥18 years who had been on mechanical ventilation for less than 72 hours, who were expected to continue for at least 24 hours, and who met criteria for baseline functional independence Exclusion criteria consisted of rapidly‐developing neuromuscular disease, cardiopulmonary arrest, irreversible disorders with 6‐month mortality estimated at more than 50%, raised intracranial pressure, absent limbs, or enrolment in another trial Age (median, in years): intervention group 58; control group 54 Percentage male: intervention group 41%; control group 58%
Interventions	Intervention: physical and occupational therapy co‐ordinated with daily interruption of sedatives consisting of: 1. passive range of motion for all limbs in unco‐operative participants (10 repetitions in all cardinal directions); 2. if interaction achieved, active assisted and active range of motion exercises in the supine position; 3. advancement to bed mobility activities including transferring to upright sitting; 4. participation in activities of daily living (ADL) and exercise, encouraging increased independence with functional tasks; and 5. transfer training, pre‐gait exercise and walking. Control: daily interruption of sedatives with physical and occupational therapy delivered as ordered
Outcomes	Functional outcomes at hospital discharge, duration of delirium, ventilator‐free days compared with standard care
Notes	2‐centre trial Time to first physiotherapy session was 1.5 days in the intervention group and 7.4 days in the control group; rates and timing of physical and occupational therapy in the control group may have been affected and the control group could have been at disadvantage No funding
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "computer generated, permuted block randomisation scheme was used"
Allocation concealment (selection bias)	Low risk	Quote: "consecutively numbered, sealed, opaque envelope"
Blinding (performance bias and detection bias) Neuromuscular analysis	Low risk	Quote: "the nature of the intervention prevented any blinding from patients and health care providers", "therapists who undertook patient assessments were blinded to treatment assignment" Comment: Review authors judge that blinding outcome assessors is probably sufficient to avoid substantial risk of bias
Blinding (performance bias and detection bias) Mortality	Low risk	Comment: Review authors judge that blinding outcome assessors was sufficient to avoid bias
Blinding (performance bias and detection bias) Other secondary outcomes	High risk	Quote: "the nature of the intervention prevented any blinding from patients and health care providers"… "Decisions about sedation initiation or reinitiation, extubation, and ICU and hospital discharge were not controlled by protocol and might have been affected by knowledge of the intervention" Comment: Unblinding could have introduced bias
Incomplete outcome data (attrition bias) Neuromuscular outcome	High risk	Quote: "Data were analysed by an intention‐to‐treat approach. Patients who died during the study were assigned scores of 0 for ventilator‐free days, strength testing (MRC examination and hand grip), ADL total, walk distance, and Barthel Index score." Comment: adequate imputation performed but this involved a substantial amount of data
Incomplete outcome data (attrition bias) Mortality	Low risk	Quote: "All 104 patients were included in the analysis"
Incomplete outcome data (attrition bias) Other secondary outcomes	Low risk	Quote: "All 104 patients were included in the analysis"
Selective reporting (reporting bias)	Low risk	Comment: The study protocol is available at www.clinicaltrials.gov. The paper reports all the prespecified outcome measures
Diagnostic criteria for CIP/CIM	Low risk	Comment: MRC sum‐score was used
Other bias	Low risk	The study appears to be free of other bias