Background: Extubation failure is an important issue in ventilated patients and its risk factors remain a matter of research. We conducted a systematic review and meta-analysis to explore factors associated with extubation failure in ventilated patients who passed a spontaneous breathing trial and underwent planned extubation. This systematic review was registered in PROPERO with the Registration ID CRD42019137003. Methods: We searched the PubMed, Web of Science and Cochrane Controlled Register of Trials for studies published from January 1998 to December 2018. We included observational studies involving risk factors associated with extubation failure in adult intensive care unit patients who underwent invasive mechanical ventilation. Two authors independently extracted data and assessed the validity of included studies. Results: Sixty-seven studies (involving 26,847 participants) met the inclusion criteria and were included in our meta-analysis. We analyzed 49 variables and, among them, we identified 26 factors significantly associated with extubation failure. Risk factors were distributed into three domains (comorbidities, acute disease severity and characteristics at time of extubation) involving mainly three functions (circulatory, respiratory and neurological). Among these, the physiological respiratory characteristics at time of extubation were the most represented. The individual topic of secretion management was the one with the largest number of variables. By Bayesian multivariable meta-analysis, twelve factors were significantly associated with extubation failure: age, history of cardiac disease, history of respiratory disease, Simplified Acute Physiologic Score II score, pneumonia, duration of mechanical ventilation, heart rate, Rapid Shallow Breathing Index, negative inspiratory force, lower PaO₂/FiO₂ ratio, lower hemoglobin level and lower Glasgow Coma Scale before extubation, with the latest factor having the strongest association with extubation outcome. Conclusions: Numerous factors are associated with extubation failure in critically ill patients who have passed a spontaneous breathing trial. Robust multiparametric clinical scores and/or artificial intelligence algorithms should be tested based on the selected independent variables in order to improve the prediction of extubation outcome in the clinical scenario.

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk–benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26–41) versus 29% (IQR: 17–38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14–1.90 versus 1.00 (95% CI: 0.87–1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08–1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80–1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09–1.93] vs. 1.09 [95% CI: 0.93–1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.