In a multicenter RCT of 7000 critically ill patients, resuscitation with 6% HES (130/0.4) did not significantly reduce 90-day mortality compared to saline (18% vs. 17%; P = 0.26). HES increased the need for renal replacement therapy (7.0% vs. 5.8%; P = 0.04, NNH = 83) and acute kidney injury (38.0% vs. 34.6%; P = 0.005) and was associated with more adverse events, including pruritus and rash. These findings suggest HES should not be used for fluid resuscitation in critically ill patients.

In a multicenter RCT of 804 patients with severe sepsis, fluid resuscitation with 6% HES (130/0.42) significantly increased the composite outcome of 90-day mortality or dependence on dialysis compared to Ringer's acetate (51% vs. 43%; P = 0.03, NNH = 13). HES also increased the need for renal replacement therapy (22% vs. 16%; P = 0.04, NNH = 17). These findings strongly discourage the use of HES for resuscitation in septic ICU patients.

This multicenter, open-label RCT compared trophic enteral feeding (20 kcal/h) with full enteral feeding (25–30 kcal/kg/day) over 6 days in 1000 mechanically ventilated patients with ARDS (PaO₂/FiO₂ <300). Ventilator-free days (14.9 vs. 15, p=0.89), 60-day mortality (23.2% vs. 22.2%, p=0.77), and infectious complications were similar. Trophic feeding reduced gastrointestinal intolerance (gastric residuals 2.2% vs. 4.9%, p<0.001). Findings support initiating early enteral feeding with escalation as tolerated.

This multicenter, double-blinded RCT evaluated early neuromuscular blockade with cisatracurium in 340 patients with moderate to severe ARDS (PaO₂/FiO₂ <150). Adjusted 90-day mortality was lower in the cisatracurium group (HR 0.68, 95% CI 0.48–0.98, p=0.04), though crude mortality was not significantly different (31.6% vs. 40.7%, p=0.08). Subgroup analysis suggested benefits in patients with PaO₂/FiO₂ <120 (30.8% vs. 44.6%, p=0.04). Limitations include reduced statistical power. Findings support early neuromuscular blockade in severe ARDS.

In a multicenter RCT of 1679 patients with shock, dopamine did not significantly reduce 28-day mortality compared to norepinephrine (52.5% vs. 48.5%; P = 0.10). Dopamine caused more arrhythmias (24.1% vs. 12.4%; P < 0.001) and was associated with higher mortality in cardiogenic shock (subgroup P = 0.03). Norepinephrine was more effective in maintaining target blood pressure. Findings support norepinephrine as the preferred first-line vasopressor for all shock types.

In a multicenter RCT of 1508 critically ill patients with acute kidney injury, higher-intensity dialysis (40 ml/kg/hour) did not improve 90-day mortality compared to lower-intensity dialysis (25 ml/kg/hour) (44.7% in both groups; P = 0.99). Need for RRT at 90 days and subgroup outcomes, including severe sepsis, were similar. Hypophosphatemia was more common with high-intensity therapy. These findings do not support routine use of higher-intensity renal replacement therapy.

In a multicenter RCT of 6104 ICU patients, intensive glucose control (81–108 mg/dL) increased 90-day mortality compared to conventional control (<180 mg/dL) (27.5% vs. 24.9%; P = 0.02) and significantly raised the risk of severe hypoglycemia (6.8% vs. 0.5%; P < 0.001). Secondary outcomes, including ICU/hospital length of stay and organ support days, were similar. Findings support targeting blood glucose <180 mg/dL in critically ill patients to avoid harm associated with intensive glucose control.

In a multicenter RCT of 778 patients with septic shock, low-dose vasopressin did not significantly reduce 28-day mortality compared to norepinephrine (35.4% vs. 39.3%; P = 0.26). Subgroup analysis suggested potential benefit in less severe septic shock but not in severe cases. Vasopressin showed no differences in adverse events, organ dysfunction-free days, or renal replacement therapy needs. These findings support vasopressin as a catecholamine-sparing agent rather than a mortality-reducing therapy.

In a multicenter RCT of 499 patients with septic shock, hydrocortisone did not improve 28-day mortality compared to placebo (34.3% vs. 31.5%; P = 0.51), regardless of response to a corticotropin test. However, hydrocortisone significantly hastened shock reversal (3.3 vs. 6.9 days; P < 0.001). Hydrocortisone was associated with increased hyperglycemia (85% vs. 72%) and superinfections (33% vs. 26%). These findings suggest hydrocortisone may benefit select patients but do not support routine corticotropin testing.

In a multicenter RCT of 1460 critically ill patients, epoetin alfa did not significantly reduce RBC transfusion rates (46% vs. 48.3%; P = 0.34) or overall 29-day mortality (8.5% vs. 11.4%; HR 0.79, 95% CI 0.56–1.10). Hemoglobin levels were higher with epoetin alfa (1.6 g/dL vs. 1.2 g/dL; P < 0.001), but thrombotic events increased (16.5% vs. 11.5%; P = 0.008). In trauma patients, 29-day mortality improved (3.5% vs. 6.6%; NNT = 32). Routine use is not recommended; further research is needed in trauma patients.

This randomized, double-blind trial investigated low-dose extended methylprednisolone infusion versus placebo in 91 patients with early severe ARDS (<72 h). Methylprednisolone significantly improved lung function, with more patients achieving a 1-point reduction in lung injury score (69.8% vs. 35.7%, p=0.002) and successful extubation by day 7 (54.0% vs. 25.0%, p=0.01). Secondary outcomes favored treatment, including reduced ICU mortality (20.6% vs. 42.9%, p=0.03), shorter ICU stays (7 vs. 14.5 days, p=0.007), and lower infection rates (15.9% vs. 28.6%, p=0.0002). Findings suggest potential benefits of methylprednisolone in early severe ARDS, warranting larger trials for confirmation.

In a multicenter RCT of 1000 patients with ALI/ARDS, a conservative fluid strategy did not significantly reduce 60-day mortality compared to a liberal strategy (25.5% vs. 28.4%; P = 0.30). However, it improved oxygenation index, lung injury scores, ventilator-free days (14.6 vs. 12.1; P < 0.001), and ICU-free days (13.4 vs. 11.2; P < 0.001). Conservative fluid management did not increase shock or dialysis use, supporting its use to enhance lung recovery and reduce ICU dependency in ALI/ARDS patients.