Thirty-five trials were included (participants ranged from 32 to 20,211). Most (23) trials were single centre studies and all except one had a parallel design (one was a cross-over trial). Twelve trials had adequate randomisation, 13 had adequate allocation concealment, four had blinded outcome assessment and 31 had loss to follow-up less than 10%. Only one trial satisfied all quality criteria.
Blood and blood saving strategies (seven trials, 1,374 participants)
Two trials evaluated blood product administration but found no significant differences in mortality (both trials), microvascular bleeding or coagulation (one trial each). Five trials evaluated methods of reducing allogeneic blood use. Cell salvage at 24 hours significantly reduced transfusion (one trial) and blood substitute significantly reduced red blood cell requirements (three trials). PolyHeme significantly increased prolonged prothrombin time and activated partial thromboplastin time, but there was an imbalance in these outcomes at baseline (one trial). Two out of four blood substitute trials reported mortality and found no significant differences.
Mechanical and surgical management (two trials, 257 participants)
One trial evaluated the use of pneumatic anti-shock garments for traumatic injury and found a trend towards increased mortality with the garments. The other evaluated vascular control of renal vessels during surgery for kidney injury and found no effect for intra-operative blood loss. Neither trial found any difference in transfusion requirements or reported on coagulation.
Intravenous fluids for resuscitation (18 trials, 3,394 participants)
Twelve trials compared different resuscitation fluids (full details reported in paper). Six reported fluid administration strategies. One trial found significant reductions in mortality at 24 hours and 30 days with hypertonic saline dextran but this was not seen in six other trials of the same intervention. One trial of continuous arteriovenous rewarming also found a significant reduction in 24 hour mortality but not at discharge. One trial reported a significant increase in acute respiratory distress syndrome after albumin administration. One trial found a significant difference in infection rates following Plasma Protein Fraction infusion. There were no differences for multi-organ failure (two trials). One trial found a significant reduction in red blood count use at one hour with pentastarch, another throughout resuscitation with hypertonic solutions, and a third in the first hour after use of a rapid infuser. Three trials reported significant improvements in clotting parameters. Ten out of 12 trials found no differences in transfusion requirements.
Pharmaceutical agents (eight trials, 21,689 participants)
Three trials evaluated antifibrinolytics (two aprotinin, one tranexamic acid), four publications (from three trials) evaluated recombinant factor VIIa and two trials evaluated novel drugs (a bactericidal protein and a monoclonal antibody). All trials reported mortality and one assessing tranexamic acid found significant reductions in all-cause mortality and death from bleeding. For recombinant factor VIIa, one trial found a significant reduction in multi-organ failure rates in blunt trauma patients surviving more than 48 hours and one trial found a significant reduction in acute respiratory distress syndrome. Two other trials also found significant reductions in acute respiratory distress syndrome. This treatment also led to significant reductions in red blood cell use in blunt trauma and coagulopathic patient subgroups and greater numbers of massive transfusions if their post study prothrombin time remained elevated at one hour.