Prevention and Management of Acute Chest Syndrome Without Automated Red Cell Exchange Among Patients With Sickle Cell Disease Not Requiring <scp>ICU</scp> Care: A Systematic Review and Network Meta‐Analysis

Acute chest syndrome (ACS) is a severe complication of sickle cell disease (SCD) associated with significant morbidity and mortality, necessitating optimized prevention and management strategies for improved patient outcomes. This review does not evaluate red blood cell exchange, as no randomized controlled trials meeting our inclusion criteria reported outcomes for this intervention. A thorough literature review identified interventions for ACS in SCD patients. Seventeen randomized controlled trials (RCTs) underwent assessment using the Cochrane Risk of Bias 2 tool, and a frequentist network meta-analysis was conducted to compare interventions. The use of hydroxyurea and simple transfusion was associated with a lower proportion of patients who developed ACS during the study period compared with standard care (RR: 0.42, 95% CI [0.20-0.86]; RR: 0.31, 95% CI [0.12-0.75], respectively). Intravenous dexamethasone was associated with a lower risk of persistent fever, reduced need for blood transfusion, and shorter durations of both opioid and oxygen therapy, as well as a shorter in-hospital stay (p < 0.01 for all comparisons). When compared with standard care, hydroxyurea was associated with reduced requirement for blood transfusion (RR: 0.17, 95% CI [0.04, 0.73]), with a similar association observed for intravenous dexamethasone (RR: 0.19, 95% CI [0.05, 0.77]). No significant associations were identified between any treatment and rates of hospitalization or readmission. This study offers insights into ACS treatment efficacy and safety in SCD patients. Hydroxyurea and transfusion strategies demonstrated the strongest evidence for reducing acute chest syndrome risk. Corticosteroids were associated with improved inpatient outcomes in predominantly pediatric populations, but concerns regarding potential rebound pain and rehospitalization warrant cautious interpretation. Larger trials are required before routine steroid use can be broadly recommended.