Citations

Rationale: Neuromuscular blocking agents (NMBAs) show potential benefits on mortality and other complications of acute respiratory distress syndrome (ARDS) in adult patients. Evidence-based decisions and processes ensure appropriate use of neuromuscular blockade in adult patients with ARDS. Objectives: The objective of these guidelines was to develop evidence-based recommendations for the administration of NMBAs in critically ill adult patients with ARDS. Design: The American College of Critical Care Medicine Board convened a 21-member multidisciplinary panel of experts in critical care medicine, nursing, respiratory therapy, pharmacology, surgery, neurology, and anesthesiology. The panel included two expert methodologists specialized in developing evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guidelines development including task force selection and voting. Methods: The panel members identified and formulated five Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and assessed the certainty of the evidence using the GRADE methodology. We used the GRADE evidence-to-decision framework to formulate the recommendations. Results: The panel generated two conditional recommendations. One recommendation is to use NMBAs in adults with ARDS with Pa o 2 /F io 2 less than 150. For the other recommendations, there was equipoise in the recommendation for and against using titratable vs. fixed-dose NMBA dosing, a monitoring-based strategy for assessing depth of sedation and analgesia in adults with ARDS before initiating or while receiving neuromuscular blockade, and administration of NMBAs for patients who are proned, due to overall lack of evidence in critically ill patients and due to considerations of patient safety and experience concerns. Conclusions: These guidelines provide additional perspectives on the use of NMBA in patients with ARDS, recognizing that institutional and patient-specific considerations must help to guide the decision-making process.

OBJECTIVES: Acute hypoxemic respiratory failure in immunocompromised patients remains the leading cause of admission to the ICU, with high case fatality. The response to the initial oxygenation strategy may be predictive of outcome. This study aims to assess the response to the evolutionary profiles of oxygenation strategy and the association with survival. DESIGN: Post hoc analysis of EFRAIM study with a nonparametric longitudinal clustering technique (longitudinal K-mean). SETTING AND PATIENTS: Multinational, observational prospective cohort study performed in critically ill immunocompromised patients admitted for an acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1547 patients who did not require invasive mechanical ventilation (iMV) at ICU admission were included. Change in ventilatory support was assessed and three clusters of change in oxygenation modality over time were identified. Cluster A: 12.3% iMV requirement and high survival rate, n = 717 patients (46.3%); cluster B: 32.9% need for iMV, 97% ICU mortality, n = 499 patients (32.3%); and cluster C: 37.5% need for iMV, 0.3% ICU mortality, n = 331 patients (21.4%). These clusters demonstrated a high discrimination. After adjustment for confounders, clusters B and C were independently associated with need for iMV (odds ratio [OR], 9.87; 95% CI, 7.26–13.50 and OR, 19.8; 95% CI, 13.7–29.1). CONCLUSIONS: This study identified three distinct highly performing clusters of response to initial oxygenation strategy, which reliably predicted the need for iMV requirement and hospital mortality.

Importance Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings. Objective To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine. Evidence Review A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor ( The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine ) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate. Findings In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria. Conclusions and Relevance Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

BACKGROUND: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. METHODS: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subjects who were immunocompromised and with ARF admitted to the ICU. Subjects with solid tumors admitted to the ICU with ARF were included in the analysis. RESULTS: Among the subjects from the EFRAIM cohort, 529 subjects with solid tumors (32.8%) were included in the analysis. At ICU admission, the median (interquartile range) Sequential Organ Failure Assessment score was 5 (3–9). The types of solid tumor were mostly lung cancer ( n = 111, 21%), breast cancer ( n = 52, 9.8%), and digestive cancer ( n = 47, 8.9%). A majority, 379 subjects (71.6%) were full code at ICU admission. The ARF was caused by bacterial or viral infection ( n = 220, 41.6%), extrapulmonary sepsis ( n = 62, 11.7%), or related to cancer or treatment toxicity ( n = 83, 15.7%), or fungal infection ( n = 23, 4.3%). For 63 subjects (11.9%), the ARF etiology remained unknown after an extensive diagnostic workup. The hospital mortality rate was 45.7% ( n = 232/508). Hospital mortality was independently associated with chronic cardiac failure (odds ratio 1.78, 95% CI 1.09–2.92; P = .02), lung cancer (odds ratio 2.50, 95% CI 1.51–4.19; P < .001), day 1 Sequential Organ Failure Assessment score (odds ratio 1.97, 95% CI 1.32-2.96; P < .001). ARF etiologies other than infectious, related to cancer, or treatment toxicity were associated with better outcomes (odds ratio 0.32, 95% CI 0.16–0.61; P < .001). CONCLUSIONS: Infectious diseases remained the most frequent cause of ARF in subjects with solid tumors admitted to the ICU. Hospital mortality was related to severity at ICU admission, previous comorbidities, and ARF etiologies related to non-malignant causes or pulmonary embolism. Lung tumor was also independently associated with higher mortality.

ABSTRACT Background: The routine use of empiric combination therapy with aminoglycosides during critical illness is associated with uncertain benefit and increased risk of acute kidney injury. This study aimed to assess the benefits of aminoglycosides in immunocompromised patients with suspected bacterial pneumonia and sepsis. Methods: Secondary analysis of a prospective multicenter study. Adult immunocompromised patients with suspected bacterial pneumonia and sepsis or septic shock were included. Primary outcome was hospital mortality. Secondary outcomes were needed for renal replacement therapy (RRT). Mortality was also assessed in neutropenic patients and in those with confirmed bacterial pneumonia. Results were further analyzed in a cohort matched on risk of receiving aminoglycosides combination. Results: Five hundred thirty-five patients were included in this analysis, of whom 187 (35%) received aminoglycosides in addition to another antibiotic effective against gram-negative bacteria. Overall hospital mortality was 59.6% (58.3% vs. 60.3% in patients receiving and not receiving combination therapy; P = 0.71). Lack of association between mortality and aminoglycosides was confirmed after adjustment for confounders and center effect (adjusted OR 1.14 [0.69–1.89]) and in a propensity matched cohort (adjusted OR = 0.89 [0.49–1.61]). No association was found between aminoglycosides and need for RRT (adjusted OR = 0.83 [0.49–1.39], P = 0.477), nor between aminoglycoside use and outcome in neutropenic patients or in patients with confirmed bacterial pneumonia (adjusted OR 0.66 [0.23–1.85] and 1.25 [0.61–2.57], respectively). Conclusion: Aminoglycoside combination therapy was not associated with hospital mortality or need for renal replacement therapy in immunocompromised patients with pulmonary sepsis.