Abstract
Background Opioid use is common in end-stage renal disease (ESRD) patients. However, safety of individual opioids and concomitant benzodiazepine use has not been studied. Objective To study the epidemiology of opioid and concomitant benzodiazepine use in ESRD population. To study the clinical safety profile of individual opioids in patients on hemodialysis. Design Retrospective analysis of the U.S. Renal Data System. A comprehensive review of the current literature was performed to update currently used opioid safety classification. Participants ESRD patients ≥18 years on hemodialysis who were enrolled in Medicare A and B and Part D between 2006 and 2012, excluding those with malignancy. Main Measures Hospital admission with diagnosis of prescription opioid overdose within 30, 60, and 90 days of prescription; death due to opioid overdose. Results Annually, the percentage of patients prescribed any opioid was 52.2%. Overall trend has been increasing except for a small dip in 2011, despite which the admissions due to opioid overdose have been rising. 30% of those who got a prescription for opioids also got a benzodiazepine prescription. 56.5% of these patients received both prescriptions within a week of each other. Benzodiazepine use increased the odds of being on opioids by 3.27 (CI 3.21–3.32) and increased the odds of hospitalization by 50%. Opioids considered safe such as fentanyl and methadone were associated with 3 and 6 folds higher odds of hospitalization within 30 days of prescription. Hydrocodone had the lowest odds ratio (1.9, CI 1.8–2.0). Conclusions Concurrent benzodiazepine use is common and associated with higher risk of hospitalization due to opioid overdose. Possible opioid-associated hospital admission rate is 4-5 times bigger in ESRD population than general population. Current safety classification of opioids in these patients is misleading, and even drugs considered safe based on pharmacokinetic data are associated with moderate to very high risk of hospitalization. We propose a risk-stratified classification of opioids and suggest starting to use them in all ESRD patients.
Highlights
Pain is a distressing symptom in patients with end-stage renal disease (ESRD), affecting over 50% of population [1,2,3,4]
It has a negative impact on multiple patient outcomes such as quality of life, depression, and adherence to dialysis [5, 6] that are strongly associated with higher morbidity and mortality [7]
We looked at hospital admissions due to prescription opioid overdose within 30, 60, and 90 days of an opioid prescription. e limitation of this method was that the codes for opioid overdose did not indicate if the overdose happened due to intentional self-harm, accidental overdose, or due to deteriorating renal function without adjustment of opioid dosage
Summary
Pain is a distressing symptom in patients with end-stage renal disease (ESRD), affecting over 50% of population [1,2,3,4]. The categorical classification is largely derived from small pharmacokinetic studies done on dialysis patients or case reports, and it lacks the safety demonstrations for their long-term clinical use. These guidelines do not provide any guidance regarding the concomitant use of benzodiazepines, which could be a marker for substance use, and known risk factors for increased hospitalizations and mortality in general population. We propose a risk-stratified classification of opioids and suggest starting to use them in all ESRD patients
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