O-3 Opioids, benzodiazepines, anti-cholinergic load and clinical outcomes in patients with advanced cancer

Abstract

Background Medications used to manage symptoms in patients with cancer have associated, but poorly understood, harms. The aim of this study was to explore the temporal relationship between oral morphine equivalent daily dose (MEDD), oral diazepam equivalent daily dose (DEDD) and the daily anti-cholinergic load (ACL) with cognitive and gastrointestinal symptoms, performance status, quality of life and survival in patients receiving palliative care. Methods Secondary longitudinal analysis of cancer decedents (n=235) from a palliative care trial with multiple outcome measures. At each time-point MEDD, DEDD and ACL were calculated. Multilevel modelling was used to investigate independent associations between MEDD, DEDD and ACL, and cognitive and gastrointestinal symptoms, quality of life, performance status and survival. Results Cognitive and gastrointestinal symptoms, performance status, and quality of life worsened over time. In the adjusted multilevel analysis significance remained for worsening performance status (MEDD, p=0.001; DEDD, p<0.001; ACL p=0.035) and shorter time to death (MEDD, p<0.001; ACL, p<0.01). Conclusion Commonly used palliative medications were associated with deteriorating performance status and shorter time to death. This analysis highlights the importance of adjusting for other variables, including other medication when exploring medication-related harms. An understanding of the risk-benefit balance of medications is needed to maximise net benefit for patients. Future work to delineate interactions between classes of drugs and drug-related harms and to evaluate early assessment and management of side-effects is needed in order to maximise net benefit.