In a multicenter RCT of critically ill patients with severe AKI (KDIGO 3), a more-delayed RRT strategy (initiated only upon mandatory indications or BUN >140 mg/dL) did not increase RRT-free days compared to a delayed strategy (BUN >112 mg/dL or >72 hours oliguria) (median 12 days for both; P = 0.93). Mortality at 60 days was higher with the more-delayed strategy (HR 1.65, 95% CI 1.09–2.50, P = 0.018). Early RRT initiation within 72 hours is recommended.

This multicenter RCT evaluated high-dose 24-hour tranexamic acid infusion versus placebo in 11,937 adults with acute gastrointestinal bleeding. Death from bleeding within 5 days was similar (3.7% vs. 3.8%; RR 0.99, 95% CI 0.82–1.18). Tranexamic acid increased venous thromboembolic events (0.8% vs. 0.4%; RR 1.85, 95% CI 1.15–2.98) and seizures (0.6% vs. 0.4%; RR 1.73, 95% CI 1.03–2.93). Secondary outcomes, including rebleeding and all-cause mortality, were comparable. Findings indicate no mortality benefit with tranexamic acid and highlight safety concerns, warranting further subgroup analyses.

In a multicenter RCT, no sedation did not reduce 90-day mortality compared to light sedation (42.4% vs. 37.0%; P = 0.65) in mechanically ventilated patients. Secondary outcomes, including ventilator-free and ICU-free days, were similar. Non-sedation reduced thromboembolic events (0.3% vs. 2.8%) but increased accidental extubations (8.9% vs. 4%). These findings support targeting light sedation (RASS -2 to 1) with daily interruptions rather than no sedation

In a multicenter RCT of 2463 elderly patients with vasodilatory shock, targeting permissive hypotension (MAP 60–65 mmHg) did not significantly reduce 90-day mortality compared to standard care (41% vs. 43.8%; ARD −2.85%, 95% CI −6.75 to 1.05; P = 0.15). Vasopressor exposure was lower in the permissive hypotension group. Subgroup analysis suggested potential mortality benefit in patients with chronic hypertension. Permissive hypotension appears safe and may be a reasonable approach in elderly patients.

In a multicenter RCT of 277 patients with moderate to severe ARDS, dexamethasone significantly increased ventilator-free days (12.3 vs. 7.5 days; P < 0.0001) and reduced 60-day mortality (21% vs. 36%; P = 0.0047; NNT = 7) compared to standard care. Adverse events were similar between groups. Findings support dexamethasone use in ARDS, especially cases related to sepsis or pneumonia. Further research is needed for ARDS of other etiologies, such as trauma.

In a multicenter RCT of 581 comatose survivors of cardiac arrest due to non-shockable rhythm, moderate hypothermia (33°C) significantly improved 90-day survival with favorable neurological outcomes compared to normothermia (10.2% vs. 5.7%; P = 0.04; NNT = 22). Ninety-day mortality (81.3% vs. 83.2%) and adverse events were similar between groups. These findings support the use of therapeutic hypothermia in non-shockable cardiac arrest patients to improve neurologic outcomes.

In a multicenter RCT of 1006 patients with moderate to severe ARDS (PaO₂/FiO₂ <150), 48-hour continuous cisatracurium infusion with deep sedation did not reduce 90-day mortality compared to usual care with lighter sedation (42.5% vs. 42.8%; P = 0.93). Secondary outcomes, including ventilator-free and ICU-free days, were also similar. Routine neuromuscular blockade is not supported and should be reserved for select cases, such as ventilator asynchrony or high respiratory effort.

In a multicenter RCT of 2003 critically ill adults, adding intermittent pneumatic compression to pharmacologic thromboprophylaxis did not significantly reduce proximal deep vein thrombosis incidence compared to pharmacologic thromboprophylaxis alone (3.9% vs. 4.2%; P = 0.74). Secondary outcomes, including venous thromboembolism and 90-day mortality, were also similar. Findings do not support routine use of pneumatic compression in ICU patients receiving anticoagulant prophylaxis.

In a multicenter RCT of 424 patients with septic shock, targeting capillary refill time for resuscitation did not significantly reduce 28-day mortality compared to lactate-targeted resuscitation (34.9% vs. 43.4%; P = 0.06). Capillary refill-targeted resuscitation improved organ dysfunction at 72 hours (SOFA score 5.6 vs. 6.6; P = 0.045). Secondary outcomes, including mechanical ventilation- and vasopressor-free days, were similar. Findings suggest capillary refill targeting is a safe alternative but does not clearly improve mortality.

In a multicenter RCT of 566 ICU patients with hypoactive or hyperactive delirium, haloperidol and ziprasidone did not significantly reduce days alive without delirium or coma compared to placebo (7.9 vs. 8.7 vs. 8.5 days; P = 0.26). Secondary outcomes, including survival and time to mechanical ventilation freedom, were also similar. Findings suggest haloperidol or ziprasidone do not improve delirium duration in critically ill patients with acute respiratory failure or shock.

This multicenter RCT assessed early ECMO versus conventional mechanical ventilation in 249 severe ARDS patients (PaO₂/FiO₂ <50 for >3 hours or <80 for >6 hours, or pH <7.25 with PaCO₂ >60 mmHg for >6 hours). Early ECMO did not significantly reduce 60-day mortality (35% vs. 46%, p=0.09) but reduced treatment failure (35% vs. 58%, p<0.001). ECMO group had more bleeding events (46% vs. 28%) but no ischemic strokes. Study limitations include early termination, high crossover rates, and underpowering. Findings suggest no definitive mortality benefit of early ECMO, with secondary benefits warranting further investigation.

This multicenter, double-blind RCT investigated hydrocortisone versus placebo in 3,658 mechanically ventilated patients with septic shock requiring vasopressors. There was no difference in 90-day mortality (27.9% vs. 28.8%, p=0.50). Hydrocortisone reduced shock resolution time (3 vs. 4 days, p<0.001), ICU discharge time (10 vs. 12 days, p<0.001), mechanical ventilation cessation time (6 vs. 7 days, p<0.001), and transfusion rates (37% vs. 41.7%, p=0.004). Findings support hydrocortisone use for vasopressor-dependent septic shock to expedite recovery.