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Effect of opioids and benzodiazepines on clinical outcomes in patients receiving palliative care: an exploratory analysis

Boland, Jason W.; Allgar, Victoria; Boland, Elaine G.; Oviasu, Osaretin; Agar, Meera; Currow, David C.; Johnson, Miriam J.


Jason W. Boland

Victoria Allgar

Elaine G. Boland

Osaretin Oviasu

Meera Agar

David C. Currow


Background: Medications for symptom management in palliative care have associated, but poorly understood, harms. Drug-related harms have important clinical implications, may impact on patients’ compliance and contribute to symptoms. Objective: To explore the longitudinal relationship between oral morphine equivalent daily dose (MEDD) and oral diazepam equivalent daily dose (DEDD) with functional, cognitive and symptom outcomes. in patients receiving palliative care. Design: Secondary longitudinal analysis of cancer decedents (n=235) from a palliative care randomised controlled trial with multiple outcome measures. At each time-point, MEDD and DEDD were calculated. Multilevel modelling was used to investigate independent associations between MEDD and DEDD, and cognitive and gastrointestinal symptoms, quality of life, performance status and survival. Setting/Subjects: Participants were recruited from a specialist palliative care programme in Southern Adelaide, were expected to live ≥48 hours, had pain in the previous three months and a baseline Folstein Mini-Mental Status Examination score ≥25. Results: Cognitive and gastrointestinal symptoms, performance status, and quality of life worsened over time. In the adjusted multilevel analysis, statistically significant relationships remained between MEDD/DEDD and worsening performance status (p=0.001), DEDD and gastrointestinal effects (p<0.001), MEDD and quality of life (p<0.022). Conclusions: Commonly used palliative medications were associated with deteriorating performance status. The lack of association between MEDD with gastrointestinal or cognitive symptoms underlines that these associations are not inevitable with close attention. This analysis highlights the importance of including other medications as confounders when exploring medication-related harms. An understanding of the risk-benefit balance of medications is needed to maximise net benefits for patients.


Boland, J. W., Allgar, V., Boland, E. G., Oviasu, O., Agar, M., Currow, D. C., & Johnson, M. J. (2017). Effect of opioids and benzodiazepines on clinical outcomes in patients receiving palliative care: an exploratory analysis. Journal of palliative medicine, 20(11), 1274-1279.

Acceptance Date Apr 26, 2017
Online Publication Date Jun 1, 2017
Publication Date Nov 1, 2017
Deposit Date May 8, 2017
Publicly Available Date Jun 6, 2018
Journal Journal of palliative medicine
Print ISSN 1096-6218
Electronic ISSN 1557-7740
Publisher Mary Ann Liebert
Peer Reviewed Peer Reviewed
Volume 20
Issue 11
Pages 1274-1279
Keywords Opioids; Benzodiazepines; Palliative; Cancer; Symptoms; Disease trajectory; Survival; Quality of life; Adverse medication events
Public URL
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Copyright Statement ©2018 University of Hull
Additional Information This is the accepted manuscript of an article published in Journal of palliative medicine, 2017. The version of record is available at the DOI link in this record.


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