CUMULATIVE DRUG INTERACTION BURDEN IN INTENSIVE CARE PATIENTS: ASSOCIATION WITH POLYPHARMACY AND CLINICAL OUTCOMES

Ahmet FIRAT, Selahattin Buğra KURTOĞLU

Türk Yoğun Bakım Dergisi - 2026;24(3):194-202

Department of Intensive Care, Aksaray Training and Research Hospital, Aksaray, Türkiye

 

Objective: Potential drug-drug interactions (pDDIs) are common in intensive care units (ICUs), but whether they independently contribute to adverse clinical outcomes remains unclear because of their close association with polypharmacy. This study evaluated the associations of cumulative pDDI burden and medication burden with clinical outcomes in medical and surgical ICU patients. Materials and Methods: This retrospective cohort study included 270 adult patients admitted to the medical and surgical intensive care units between January and December 2025. Potential drug-drug interactions were identified using the Lexicomp(R) database, and the cumulative number of unique pDDIs was calculated for each patient throughout the ICU stay. Multivariable logistic and linear regression analyses were performed to examine the associations of medication burden and cumulative unique pDDI burden with in-hospital mortality, hospital length of stay, and ICU length of stay. Results: Of the 270 patients, 57.0% were admitted to medical ICUs and 43.0% to surgical ICUs. Patients in medical ICUs had higher APACHE II scores, a greater proportion of high-risk pDDIs, and higher in-hospital mortality than those in surgical ICUs (24.7% vs. 9.5%; p=0.001), whereas the total number of medications and the cumulative number of unique pDDIs were similar between the groups. In multivariable analyses, the total number of medications remained an independent predictor of in-hospital mortality and longer hospital and ICU stays. Although the cumulative number of unique pDDIs was associated with in-hospital mortality when evaluated in a separate multivariable model, this association was no longer significant after adjustment for the total number of medications. Conclusion: Although cumulative pDDI burden was associated with adverse clinical outcomes in univariable analyses, this association was largely explained by overall medication burden. These findings highlight the importance of considering overall medication burden when interpreting the clinical relevance of pDDIs in critically ill patients.