Bulger 2010.

Methods	RCT Parallel design Multicentre
Participants	Total number of randomised participants: 1331 Inclusion criteria: blunt mechanism of injury; ≥ 15 years of age; GCS score ≤ 8; ineligibility for enrolment in the haemorrhagic shock cohort Exclusion criteria: known or suspected pregnancy; < 15 years of age; out‐of‐hospital cardiopulmonary resuscitation; administration of > 2000 mL of crystalloid or any amount of colloid or blood products prior to enrolment; severe hypothermia (28 °C); drowning; asphyxia because of hanging; burns on > 20% of TBSA; isolated penetrating head injury; inability to obtain IV access; > 4 h between receipt of dispatch call to study intervention Participant condition: traumatic brain injury Baseline characteristics Colloids group Age, mean (SD): 38.5 (± 18.6) years Gender, M:F: 86:273 BP, mean (SD): SBP: 141.2 (± 33.1) mmHg Crystalloids group (NS) Age, mean (SD): 39.5 (± 19.2) years Gender, M:F: 156:426 BP, mean (SD): SBP: 139.1 (± 33.1) mmHg Crystalloids group (HS) Age, mean (SD): 38.6 (± 17.3) years Gender, M:F: 64:277 BP, mean (SD): SBP: 136.9 (± 33.5) mmHg Country: USA and Canada Setting: 11 regional clinical centres
Interventions	Colloids group Participants: n = 373; losses = 14 (5 did not meet inclusion criteria; 3 met an exclusion criterion; 4 had no IV access; 1 fluid bag sterility broke; 1 EMS responder unsure of inclusion/exclusion criteria); analysed = 359 Details: 7.5% saline in 6% dextran 70; 250 mL Additional details: single bolus; all conducted out‐of‐hospital; participants may have been given fluid before attendance of study personnel but must have only received < 2 L of crystalloid and no colloid, mannitol or blood products Crystalloids group (NS) Participants: n = 603; losses = 21 (8 did not meet inclusion criteria; 4 had inadequate time to administer; 2 met an exclusion criterion; 4 had no IV access; 2 fluid bag sterility broke; 1 EMS responder unsure of inclusion/exclusion criteria); analysed = 582 Details: 0.9% saline; 250 mL Additional details: same as colloid group Crystalloids group (HS) Participants: n = 355; losses = 14 (5 did not meet inclusion criteria; 1 met an exclusion criterion; 6 had no IV access; 1 fluid bag sterility broke; 1 EMS responder unsure of inclusion/exclusion criteria); analysed = 341 Details: 7.5% saline; 250 mL Additional details: same as colloid group
Outcomes	Outcomes measured/reported: 6‐month neurologic status (Glasgow Outcome Score); 28‐day survival; survival to discharge; ICP; interventions required to manage intracranial hypertension; fluid and bolus requirements in first 24 h; physiologic parameters of organ dysfunction; 28‐day ARDS‐free survival; MODS; nosocomial infections Outcomes relevant to the review: mortality (28 days)
Notes	Funding/declarations of interest: National Heart, Lung and Blood Institute plus partners Study dates: May 2006‐May 2009 Study terminated after futility criteria met at 6 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly generated numeric code used at central location
Allocation concealment (selection bias)	Low risk	Randomisation scheme conducted externally and all personnel unaware of allocation
Blinding of participants and personnel (performance bias): mortality	Low risk	Quote: "Study fluids were provided in identical intravenous bags and shipped to a single distribution center, where they were labelled with a randomly generated numeric code" Participants, caregivers, and outcome assessors were blinded to treatment
Blinding of outcome assessment (detection bias): mortality	Low risk	Participants, caregivers, and outcome assessors were blinded to treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Mortality data reported for 359/373 (HSD), 341/355 (HS), and 582/603 (NS). < 5% dropout/loss in each group
Selective reporting (reporting bias)	Low risk	Prospective clinical trials registration: NCT00316004. All outcomes were prespecified
Baseline characteristics	Low risk	Baseline characteristics appear comparable
Other bias	Low risk	No other sources of bias identified