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Levodopa Administration Timing During Hospitalization: Associations With Intensive Care Unit Exposure and Documented Access Type

Year: 2026

Type: preprint

Abstract: Background Levodopa is time-critical in hospitalized Parkinson disease. Whether dosing fidelity depends on care setting or documented access status is unclear. Objectives To quantify levodopa dosing fidelity, test ICU exposure with clustering-aware methods, and test whether documented access type is associated with delayed or omitted dosing. Methods Retrospective cohort study using MIMIC-IV (2011-2022). Adults with Parkinson disease and ≥1 scheduled levodopa dose contributed 1,665 admissions and 39,322 doses. ICU exposure was tested with a patient-clustered GEE model. Among ICU-exposed doses, access type (normal, tube feeding, parenteral nutrition, NPO) was modeled in one fully adjusted model and tested for specificity, restricted to the ICU, against an active-comparator medication (statins). Results Of 39,322 doses, 79.8% were on time by the primary 60-minute definition; a symmetric ±15-minute definition classified 68.8% as mistimed. ICU exposure was not associated with delayed or omitted dosing after clustering (patient-clustered OR, 0.87; 95% CI, 0.74-1.01). Among ICU-exposed doses, NPO was associated with delayed or omitted dosing (adjusted OR, 1.89; 95% CI, 1.36-2.62) and tube feeding with lower odds (adjusted OR, 0.62; 95% CI, 0.42-0.92; P < .001). The comparator medication showed a directionally consistent but inconclusive interaction (OR, 1.27-1.28; 92 patients). A route-order association was not observed among immediate-release formulations (OR, 0.72; 4 patients). Conclusions ICU admission alone was not associated with dosing unreliability after clustering. Among ICU-exposed doses, access type, not a single pooled category, was associated with dosing reliability; a comparator-medication check, valid only in the ICU, was directionally consistent but inconclusive.

Source: medRxiv

DOI: 10.64898/2026.08.17.26360596

Authors: Alon Gorenshtein, Mark Katson, Yosef Adiniaev, Eyal Klang, Oved Daniel

Institutions: Beth Israel Deaconess Medical Center, Harvard University, Tel Aviv Sourasky Medical Center

Language: English

Topic: Patient Safety and Medication Errors

Subfield: Emergency Medical Services

Field: Health Professions

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Harvard Catalyst, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Center for Advancing Translational Sciences