Mortality Associated with Intensive Care Unit Admission and Mechanical Ventilation in Adults with Acute Chest Syndrome: A Systematic Review.

Background and Objectives: Acute chest syndrome (ACS) is the leading cause of sickle cell disease (SCD)-related mortality (~25% of deaths). A subset of patients develops severe respiratory compromise requiring intensive care unit (ICU) admission or mechanical ventilation (MV), a high-risk group with widely variable reported mortality. This review aimed to determine the mortality rates, ICU/hospital length of stay, and reported complications among adult SCD patients with ACS admitted to the ICU or placed on MV. Materials and Methods: This PRISMA 2020-compliant systematic review was prospectively registered on PROSPERO (CRD420261295111). Cochrane Library, PubMed, Web of Science, ScienceDirect, EBSCOhost, and Scopus were searched without date restriction. Due to substantial clinical and methodological heterogeneity, the pre-specified meta-analysis was replaced by a narrative synthesis. Methodological quality was assessed using the Newcastle-Ottawa Scale. Results: Eight studies were included (one multicenter prospective cohort, two national database studies, three single-center cohorts, and one before-after antimicrobial stewardship study). In-hospital mortality ranged from 0.95% to 3.8%; overall mortality including follow-up reached 12.9% in a dedicated ICU cohort, a distinct endpoint from in-hospital death. Mechanical ventilation was the strongest indicator of mortality, with odds ratios of 67.53 (MV < 96 h) and 8.73 (MV ≥ 96 h) in the largest national cohort. Tricuspid regurgitant jet velocity ≥3 m/second was associated with cor pulmonale, invasive ventilation, and all immediate hospital deaths in one severe cohort. Documented bacterial infection was uncommon (10-20% of episodes), despite frequent antibiotic use, and procalcitonin-guided discontinuation safely reduced antibiotic exposure. All eight included studies were rated high quality on the Newcastle-Ottawa Scale (score ≥ 7/9). Conclusions: Mechanical ventilation, pulmonary hypertension/cor pulmonale, and comorbidity burden are the most consistent markers of poor outcome in ACS. The findings support early recognition, severity-based respiratory support, and antimicrobial stewardship, but should be interpreted cautiously given the substitution of narrative synthesis for meta-analysis, heterogeneous populations, and the geographic concentration of the included studies.