Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Noninvasive ventilation in acute hypoxemic respiratory failure: A systematic review and meta-analysis.

PURPOSE: Evaluate current recommendation for the use of noninvasive ventilation (Bi-level positive airway pressure- BiPAP modality) in hypoxemic acute respiratory failure, excluding chronic obstructive pulmonary disease. METHODS: Electronic searches in MEDLINE, Web of Science, Clinical Trials, and The Cochrane Central Register of Controlled Clinical Trials. We searched for randomized controlled trials comparing BiPAP to a control group in patients with hypoxemic acute respiratory failure. Endotracheal intubation and death were the assessed outcomes. RESULTS: Of the 563 studies found, nine met the inclusion criteria for this systematic review. The pooled RR (95% CI) for intubation in patients with acute pulmonary edema (APE)/community acquired pneumonia (CAP) and in immunosuppressed patients (cancer and transplants) were 0.61 (0.39-0.84) and 0.77 (0.60-0.93), respectively. For Intensive Care Units (ICU) mortality, the RR (95% CI) in patients with APE/CAP was 0.51 (0.22-0.79). The heterogeneity was low in all comparisons. CONCLUSIONS: NIV showed a significant protective effect for intubation in immunosuppressed patients (cancer and transplants) and in patients with APE/CAP. However, the benefits of NIV for other etiologies are not clear and more trials are needed to prove these effects.