Background: Sickle cell disease (SCD) is associated with frequent hospitalizations and significant morbidity. Polysubstance use introduces additional clinical challenges, potentially influencing treatment decisions and outcomes. However, disparities in inpatient care for SCD patients with polysubstance use remain underexplored. This study aimed to evaluate whether hospitalized SCD patients with documented polysubstance use exhibit differences in baseline characteristics, morbidity burden, and receipt of standard treatments compared to those without polysubstance use.

Methods: We conducted a retrospective cross-sectional analysis of the National Inpatient Sample (2016–2020), identifying SCD-related hospitalizations using ICD-10 codes. Cohorts were stratified by documented polysubstance use. We compared demographic, socioeconomic, and clinical variables, including age, sex, insurance type, income quartile, comorbidity burden (Charlson Comorbidity Index), and geographic distribution. Clinical outcomes and treatments including transfusions, dialysis, mechanical ventilation, vasopressor use, and exchange transfusion were assessed. Categorical comparisons used chi-squared tests, continuous variables used t-tests (significance at p<0.05), and logistic regression was performed to identify independent predictors of polysubstance use.

Results: Among >900,000 weighted SCD hospitalizations, patients with polysubstance use were older on average (36.3 vs 30.3 years, p<0.001), had a higher Charlson Comorbidity Index (1.38 vs 1.16, p<0.001), and experienced longer lengths of stay (5.22 vs 5.06 days, p<0.001). Polysubstance users were disproportionately male (52.2% vs 65.5% female in non-users, p<0.001), more likely to reside in low-income ZIP codes (55.4% vs 47.6%, p<0.001), and more often relied on Medicare or Medicaid. Clinical complications were more prevalent in polysubstance users, including higher rates of acute kidney injury (10.2% vs 7.3%, p<0.001), sepsis (6.0% vs 4.6%, p<0.001), multiorgan failure (23.7% vs 18.3%, p<0.001), venous thromboembolism (3.8% vs 2.8%, p<0.001), pain crisis (49.4% vs 40.5%, p<0.001), and chronic kidney disease (10.7% vs 9.4%, p<0.001). Despite this increased morbidity burden, there were no significant differences in key inpatient treatments such as transfusion rates (16.0% vs 16.1%, p=0.232), dialysis use (1.1% both groups, p=0.796), mechanical ventilation (1.6% both groups, p=0.706), and vasopressor use (0.3% both groups, p=0.209). Exchange transfusion rates were slightly lower in polysubstance users (15.3% vs 15.5%, p=0.013).Conclusion: Hospitalized SCD patients with documented polysubstance use demonstrate significantly higher rates of clinical complications and greater overall comorbidity burden. However, they receive comparable rates of standard inpatient treatments, including transfusion and dialysis, suggesting potential disparities in care delivery that may not fully account for their increased complexity and morbidity. These findings underscore the need for targeted strategies to ensure equitable treatment and management for SCD patients with polysubstance use disorders.

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2025
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