Key Findings
- Purpose
To evaluate whether intravenous (IV) diphenhydramine use is associated with new-onset acute chest syndrome (ACS) among adults hospitalized for vaso-occlusive episodes (VOE), while adjusting for inpatient opioid exposure. - Population (Model)
Retrospective cohort study of 477 adults with sickle cell disease hospitalized for VOE at three hospitals in the Bronx, New York, between January 2020 and January 2024. Patients presenting with ACS on admission were excluded. Of the cohort, 207 patients (43%) received IV diphenhydramine and 47 patients (10%) developed ACS during hospitalization. - Headline Result
After adjustment for opioid exposure, IV diphenhydramine was not associated with ACS at either 1–50 mg/day (adjusted OR 0.81, 95% CI 0.39–1.68; P = .57) or >50 mg/day (adjusted OR 0.52, 95% CI 0.18–1.49; P = .22). Similarly, IV diphenhydramine was not associated with ICU transfer or hospital length of stay. In contrast, higher daily opioid exposure, measured as morphine milligram equivalents (MME), was significantly associated with ACS (OR 1.03; P < .01) and longer hospital stays (OR 1.05; P < .01). - Why It Matters
Concerns have persisted that IV diphenhydramine, particularly when administered alongside opioids, may contribute to respiratory complications during VOE admissions. In this study, no significant association was observed between IV diphenhydramine use and ACS, ICU transfer, or length of stay after adjustment for opioid exposure. The observed relationship between higher opioid requirements and ACS suggests that opioid dose may reflect greater disease severity or could contribute to respiratory outcomes, as discussed by the authors.
- Evidence Gaps & Limitations
This retrospective study cannot establish causality. The authors note temporal ambiguity between diphenhydramine administration and ACS onset, the possibility of unmeasured confounding related to VOE severity, and limited generalizability beyond the Bronx, New York hospitals included in the study. Additional prospective studies are needed to further evaluate the role of antihistamines and opioid exposure during VOE hospitalizations.
Source: Journal of Sickle Cell Disease- “Diphenhydramine is not associated with poor outcomes among hospitalized people with sickle cell disease”
Regulatory & Guideline Watch
Prior National Heart, Lung, and Blood Institute guidance has favored oral rather than IV antihistamines when feasible because of concerns regarding sedation, particularly when combined with opioid therapy. This study found that IV diphenhydramine was not associated with ACS, ICU transfer, or length of stay after adjustment for opioid exposure, providing additional observational data relevant to ongoing discussions about inpatient VOE management.