In a multicenter trial of 553 critically ill children requiring non-invasive respiratory support post-extubation, HFNC (50.5 hrs) failed to demonstrate non-inferiority to CPAP (42.9 hrs) for time to liberation from respiratory support (adjusted HR 0.83; 1-sided 97.5% CI, 0.70–∞). Secondary 180-day mortality was higher with HFNC (5.6% vs. 2.4%). Findings suggest CPAP may be preferred for post-extubation respiratory support in young childre

In a phase II trial of esmolol for septic shock, no significant differences were found in norepinephrine-equivalent dose, time to shock reversal, or inflammatory markers (except lower CRP in the esmolol group). Reduced oxygen consumption was noted in a subset of esmolol patients. While prior studies suggested improved hemodynamics and mortality benefits, this trial highlights the need for a large, well-powered RCT to evaluate patient-centered outcomes of esmolol in septic shock.

In a multicenter RCT of 432 patients with hemorrhagic shock and hypotension, pre-hospital resuscitation with blood products (PRBC and lyophilized plasma) did not significantly improve composite outcomes of mortality or impaired lactate clearance compared to normal saline. Individual components of the composite outcome also showed no difference. Findings suggest no advantage of blood products over saline for pre-hospital resuscitation in this setting.

In a multicenter RCT of 5037 critically ill patients, balanced multielectrolyte solution (BMES) did not significantly reduce mortality (21.8% vs. 22.0%) or the need for renal replacement therapy (12.7% vs. 12.9%) compared to saline. Serum creatinine changes were similar between groups. Findings suggest no clinical advantage of BMES over saline for critically ill patients, though limitations warrant consideration in specific contexts.

In a multicenter RCT of 172 comatose cardiac arrest survivors, intensive anti-seizure treatment to suppress rhythmic/periodic EEG activity did not improve poor neurologic outcomes at 3 months (90% vs. 92%; P = not significant) compared to standard care. Mortality was similarly high (80% vs. 82%). The anti-seizure group had longer ICU stays and ventilation duration, with >80% of patients experiencing serious adverse events in both groups. Findings do not support aggressive EEG suppression in this population.

In a phase IIb RCT of 121 patients with large vessel occlusion acute ischemic stroke who achieved successful reperfusion after thrombectomy, adjunct intra-arterial alteplase improved the likelihood of excellent neurological outcomes (mRS 0-1 at 90 days: 59.0% vs. 40.4%; P = statistically significant). These findings are promising but require validation in larger trials before altering clinical practice.

In a multicenter RCT of 1273 hospitalized patients with COVID-19-related acute hypoxemic respiratory failure, CPAP reduced the composite outcome of tracheal intubation or 30-day mortality compared to conventional oxygen therapy (36.3% vs. 44.4%; absolute difference −8%, 95% CI −15% to −1%; P = 0.03). HFNO showed no significant difference compared to COT (44.3% vs. 45.1%). Adverse events were higher with CPAP. CPAP may improve outcomes, while HFNO needs further investigation due to underpowering.

In a multicenter RCT of 1102 critically ill patients, the use of a bougie for intubation did not improve first-attempt success rates compared to a stylet (80.4% vs. 83.0%). Rates of severe hypoxemia (11.0% vs. 8.8%) and complications, including esophageal intubation (0.7% vs. 0.9%) and pneumothorax (2.5% vs. 2.7%), were similar. Findings suggest no advantage of bougie over stylet for first-attempt intubation under these conditions. Current practice remains unchanged.

In a randomized trial of 397 adult patients with out-of-hospital cardiac arrest, intravenous or intraosseous calcium administration did not improve sustained return of spontaneous circulation (19% vs. 27%; P = 0.09) compared to saline. Survival at 30 days (5.2% vs. 9.1%; P = 0.17) and favorable neurological outcomes (3.6% vs. 7.6%; P = 0.12) were also lower in the calcium group. The trial was stopped early due to potential harm. Calcium should not be administered in this setting.

In a multicenter RCT of 512 patients with in-hospital cardiac arrest, vasopressin plus methylprednisolone significantly improved return of spontaneous circulation (42% vs. 33%; RR 1.30, 95% CI 1.03–1.63; P = 0.03) compared to placebo. However, there was no difference in 30-day survival (9.7% vs. 12%; P = 0.48) or favorable neurologic outcomes (7.6% vs. 7.6%; P > 0.99). The study demonstrates short-term benefit but lacks evidence for long-term outcomes, and findings are unlikely to alter ACLS recommendations.

This multicenter RCT assessed whether lower tidal volume ventilation (≤3 mL/kg) with extracorporeal CO₂ removal (ECCO₂R) improves 90-day mortality in acute hypoxemic respiratory failure compared to conventional ventilation (6 mL/kg). Among 412 patients, in-hospital mortality was similar (41.5% vs. 39.5%, p=0.68), but ventilator-free days were fewer (7.1 vs. 9, p=0.02). Serious adverse events, including intracranial hemorrhage, were more common with ECCO₂R. The trial, underpowered due to early termination, does not support ECCO₂R use and highlights potential harm.

In a multicenter RCT of 11,052 critically ill patients, the use of balanced solution (Plasma-Lyte 148) did not significantly reduce 90-day mortality compared to saline (26.4% vs. 27.2%; HR 0.97, 95% CI 0.90–1.05; P = 0.47). AKI requiring RRT and other secondary outcomes were similar. Subgroup analysis showed higher mortality with balanced fluids in traumatic brain injury patients. Findings suggest saline is safe for ICU patients, with balanced fluids avoided in traumatic brain injury.