IV diphenhydramine is not associated with poor outcomes among hospitalized people with sickle cell disease.

Abstract Among people living with sickle cell disease (SCD), acute chest syndrome (ACS) is a potentially life-threatening complication that may occur during inpatient care for vaso-occlusive episodes (VOE). Some data suggest that IV diphenhydramine, a centrally-acting anti-histamine used to treat opioid-induced pruritis, may be associated with development of ACS. Using data from our electronic health record, we determined whether use of IV diphenhydramine was associated with new ACS, after controlling for inpatient opioid use. We performed a multi-center retrospective cohort study which included adults >21 years old admitted for VOE between January 2020 and January 2024. The primary endpoint was new onset ACS, defined as a negative initial emergency department chest X-ray followed by subsequent imaging showing pulmonary consolidation and at least one relevant clinical symptom (e.g. fever, cough, chest pain, or shortness of breath). The secondary endpoints were the requirement of increased level of care (ICU transfer) and hospital length of stay. Using three reviewers, we extracted data into a standardized and piloted instrument. We randomly selected 100 charts for double data extraction to determine reliability of our process. Opioid exposure was standardized to oral morphine milligram equivalents per day (MME/day), calculated for the entire admission or, among patients who developed ACS, prior to the diagnosis. We built multivariable logistic regression models to assess primary and secondary outcomes and report these results using odds ratios (OR) with p values. P< 0.05 was considered statistically significant. We included 477 patients in our analysis. 10% of patients developed ACS. 43% of patients received IV diphenhydramine. Use of IV diphenhydramine was not associated with ACS (OR 1.00, p=0.66), need for transfer to ICU (OR 1.79, p=0.23), or hospital length of stay (OR 0.86, p=0.52). Morphine milligram equivalents (MME/day) was associated with ACS (OR 1.03, p<0.01) and increased hospital length of stay (OR 1.05, p<0.01). Despite some indication in the published literature of the opposite, use of IV diphenhydramine was not associated with acute chest syndrome in patients with sickle cell disease. However, the incidence of acute chest syndrome was associated with higher MME/day.