In a multicenter RCT of 1241 patients with septic shock, hydrocortisone plus fludrocortisone significantly reduced 90-day mortality compared to placebo (43.0% vs. 49.1%; P = 0.03) and improved ICU discharge, hospital discharge, and 180-day mortality rates. The intervention accelerated vasopressor weaning (17 vs. 15 vasopressor-free days; P < 0.001) and organ failure resolution (14 vs. 12 organ-failure-free days; P = 0.003). Hyperglycemia was more common, but serious adverse events were similar. These findings support hydrocortisone use for septic shock requiring vasopressors.

This pragmatic, cluster-randomized, multiple-crossover trial evaluated 15,802 critically ill adults admitted to five ICUs and compared the use of balanced crystalloids (lactated Ringer’s or Plasma-Lyte A) versus saline (0.9% sodium chloride) for intravenous fluid administration. The primary outcome was a composite of major adverse kidney events (MAKE) within 30 days, including death, new renal-replacement therapy, or persistent renal dysfunction. The incidence of MAKE was significantly lower in the balanced crystalloids group (14.3%) compared to the saline group (15.4%) with a marginal odds ratio of 0.91 (95% CI, 0.84–0.99; P=0.04). Secondary outcomes, including in-hospital mortality and new renal-replacement therapy, showed nonsignificant trends favoring balanced crystalloids. The study concluded that balanced crystalloids modestly reduced the risk of adverse kidney outcomes compared to saline in critically ill adults.

In a multicenter RCT of 488 patients with septic shock and severe acute kidney injury, early initiation of renal replacement therapy (RRT) within 12 hours did not improve 90-day mortality compared to delayed initiation after 48 hours (58% vs. 54%; P = 0.38). Delayed RRT resulted in more RRT-free days (16 vs. 12 days; P = 0.006). Early RRT led to higher RRT use (97% vs. 62%; P < 0.001). These findings support delaying RRT unless emergent indications are present.

In a multicenter RCT of 706 patients with acute MI and cardiogenic shock, culprit-lesion-only PCI significantly reduced the composite outcome of 30-day mortality or renal replacement therapy (45.9% vs. 55.4%; RR 0.83, 95% CI 0.71–0.96, P = 0.01) and 30-day mortality alone (43.3% vs. 51.6%; RR 0.84, 95% CI 0.72–0.98, P = 0.03) compared to multivessel PCI. Renal replacement rates and secondary outcomes were similar. Culprit-lesion-only PCI with staged revascularization is supported as the preferred approach.

In a multicenter RCT of 1010 patients with moderate to severe ARDS, lung recruitment with PEEP titration by best respiratory-system compliance increased 28-day mortality compared to a low-PEEP strategy (55.3% vs. 49.3%; HR 1.20, 95% CI 1.01–1.42, P = 0.041). Secondary outcomes included higher 6-month mortality, fewer ventilator-free days, and increased risk of pneumothorax and barotrauma. Routine use of recruitment maneuvers is not supported, though subgroups may warrant further investigation.

In a multicenter RCT of 321 patients with catecholamine-resistant vasodilatory shock, angiotensin II significantly improved mean arterial pressure compared to placebo (69.9% vs. 23.4%; P < 0.001) and improved cardiovascular SOFA scores (−1.75 vs. −1.28; P = 0.01). Mortality at 28 days was not significantly different (46% vs. 54%; P = 0.12). While angiotensin II effectively raises blood pressure, further research is needed to assess its impact on patient-centered outcomes before widespread adoption.

In a multicenter RCT of 380 patients with severe sepsis but not septic shock, early hydrocortisone use did not significantly reduce progression to septic shock within 14 days compared to placebo (21.2% vs. 22.9%; P = 0.70). Mortality, secondary infections, weaning failure, and muscle weakness were similar between groups, though hyperglycemia was more common with hydrocortisone (90.9% vs. 81.5%; P = 0.009). These findings do not support routine early hydrocortisone use in severe sepsis.

In a multicenter RCT of 409 septic shock patients, early vasopressin use (titrated up to 0.06 U/min) did not improve kidney failure–free days compared to norepinephrine (median 9 vs. 13 days; difference −4 days, 95% CI −11 to 5). Vasopressin was associated with reduced renal replacement therapy (25.4% vs. 35.3%; difference −9.9%, 95% CI −19.3% to −0.6%) but no difference in mortality or serious adverse events. These findings do not support vasopressin as first-line therapy over norepinephrine, though potential benefits warrant further study.

In a multicenter RCT of 620 critically ill patients with severe acute kidney injury, early initiation of renal replacement therapy (RRT) did not improve 60-day mortality compared to delayed initiation (48.5% vs. 49.7%; P = 0.79). Nearly half of the delayed group avoided RRT entirely. Early RRT was associated with higher rates of catheter-related bloodstream infections (10% vs. 5%; P = 0.03). Findings support delaying RRT initiation unless clear indications are present.

In a multicenter RCT of 310 ICU patients with nonhypercapnic acute hypoxemic respiratory failure, high-flow oxygen therapy did not significantly reduce 28-day intubation rates compared to standard oxygen or noninvasive ventilation (38% vs. 47% and 50%; P = 0.18). However, high-flow oxygen improved ventilator-free days (24 vs. 22 vs. 19; P = 0.02) and lowered 90-day mortality (HR 2.01 vs. standard, P = 0.046; HR 2.50 vs. NIV, P = 0.006). Further large-scale studies are needed.

In a multicenter RCT of 895 critically ill patients, permissive underfeeding (40–60% of calorie goals) did not reduce 90-day mortality compared to standard feeding (27.2% vs. 28.9%; RR 0.94, 95% CI 0.76–1.16; P = 0.58). Secondary outcomes, including ICU- and ventilator-free days, were similar. Post-hoc analysis suggested lower renal replacement therapy rates with permissive underfeeding (7.1% vs. 11.4%; P = 0.04). Permissive underfeeding is safe but does not offer clear survival benefits.

In a multicenter RCT of 1260 patients with septic shock, early goal-directed therapy (EGDT) did not reduce 90-day mortality compared to usual care (29.5% vs. 29.2%; P = 0.90). EGDT required greater treatment intensity, with more fluids, vasopressors, and transfusions, but showed no benefit in organ support, ICU/hospital stay, or quality of life. EGDT increased costs without cost-effectiveness. These findings support focusing on adequate fluid resuscitation and early antibiotics rather than strict EGDT protocols.