In a multicenter RCT of 6997 ICU patients, resuscitation with 4% albumin showed no significant difference in 28-day mortality compared to saline (20.9% vs. 21.1%; P = 0.87). Secondary outcomes, including ICU and hospital length of stay, were also similar. Subgroup analysis suggested worse outcomes with albumin in patients with traumatic brain injury (24.5% vs. 15.1%; P = 0.009, NNH = 11). Findings support avoiding albumin in TBI patients, with no overall benefit over saline for general ICU resuscitation.

In a multicenter RCT of 256 patients with submassive PE, alteplase plus heparin significantly reduced the composite outcome of in-hospital death or clinical deterioration requiring treatment escalation compared to heparin alone (11% vs. 24.6%; P = 0.006; NNT = 7). This was primarily driven by reduced need for secondary thrombolysis. No significant differences were observed in mortality (3.4% vs. 2.2%; P = 0.71) or major bleeding (0.8% vs. 3.6%; P = 0.29). Further studies are needed before routine use can be recommended.

In a multicenter RCT of 300 patients with septic shock, hydrocortisone combined with fludrocortisone reduced 28-day mortality in corticotropin non-responders compared to placebo (53% vs. 63%; P = 0.02) and hastened vasopressor withdrawal (57% vs. 40%; P = 0.001). Adverse event rates were similar between groups. While this study supports corticosteroids in septic shock, more recent trials, such as the CORTICUS study, emphasize steroids' role in shock reversal without a survival benefit and negate the need for corticotropin testing.

In a multicenter trial of 275 patients resuscitated from cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia (32–34°C for 24 hours) significantly improved favorable neurologic outcomes at 6 months (55% vs. 39%; P = 0.009) and reduced mortality (41% vs. 55%; P = 0.02) compared to normothermia. Complication rates were similar between groups. These findings established hypothermia as a standard of care in post-cardiac arrest management to improve neurologic recovery and survival.

In a single-center RCT of 263 patients with severe sepsis, early goal-directed therapy (EGDT) significantly reduced in-hospital mortality compared to standard care (30.5% vs. 46.5%; P = 0.009) and improved APACHE II scores during the first 72 hours. However, subsequent trials (ProCESS, ARISE, and ProMISE) demonstrated no mortality benefit of strict EGDT when early fluid resuscitation and antimicrobial therapy were adequately implemented, suggesting these components are key to sepsis management.

This multicenter RCT evaluated the impact of low tidal volume ventilation (6 mL/kg, plateau pressure ≤30 cmH₂O) versus traditional higher tidal volume (12 mL/kg, plateau pressure ≤50 cmH₂O) on mortality and ventilator-free days in 861 patients with acute lung injury or ARDS. Low tidal volume reduced in-hospital mortality (31.0% vs. 39.8%, p=0.007) and increased ventilator-free days (12±11 vs. 10±11, p=0.007). Despite single blinding, this landmark trial established low tidal volume ventilation as the standard of care.

In a multicenter RCT of 838 ICU patients, restrictive transfusion strategy (Hb 7–9 g/dL) showed no significant difference in 30-day mortality compared to a liberal strategy (Hb 10–12 g/dL) (18.7% vs. 23.3%; P = 0.11). Restrictive transfusion reduced cardiac events (13.3% vs. 21%; P < 0.01) and hospital mortality (22.2% vs. 28.1%; P = 0.05). Subgroup benefits were noted in younger and less acutely ill patients. Findings support a transfusion threshold of <7 g/dL, except in active cardiac ischemia.