Abstract
Although better pain management has guided policies for opioid use over the past few decades, evidence is limited regarding how patterns of use are associated with the risk of potentially avoidable opioid-related adverse events. To estimate the risk of harms associated with opioid dose and duration of use, and to ascertain whether the risk is modified by treatment indication and age. This ad hoc cohort study followed up patients who were enrolled in a cluster randomized trial of medication reconciliation between October 1, 2014, and November 30, 2016, 12 months after they were discharged from the McGill University Health Centre in Montreal, Quebec, Canada. To be eligible for this study, patients needed to have filled at least 1 opioid prescription 3 months after discharge. Patients with a history of using methadone or buprenorphine were excluded. Data analyses were performed between February 1, 2019, and February 28, 2020. Time-varying measures of opioid use included current use, daily morphine milligram equivalent (MME) dose, cumulative and continuous use duration, and type of ingredients in prescription opioids used. Hospitalization records, dispensed prescriptions records, and postdischarge interviews were used to evaluate adherence to the opioid prescriptions after discharge. Opioid-related emergency department visits, hospital readmissions, or all-cause death. Outcomes were ascertained using provincial medical services claims and hospitalization databases. Of 3486 participants in the cluster randomized trial (mean [SD] age of 69.6 [14.9] years; 2010 men [57.7%]), 1511 patients were included in this ad hoc cohort study. Among those with at least 1 opioid dispensation, 241 patients (15.9%) experienced an opioid-related emergency department visit, hospital readmission, or death. Results from marginal structural Cox proportional hazards regression models showed more than a 2-fold increase in the risk of opioid-related adverse events associated with a cumulative use duration of more than 90 days (adjusted hazard ratio, 2.56; 95% CI, 1.25-5.27) compared with 1 to 30 days. A 3-fold risk increase was found with a mean daily dose higher than 90 MME (adjusted hazard ratio, 3.51; 95% CI, 1.58-7.82) compared with 90 MME or lower. This study found an association between risk of adverse health care events and higher opioid doses and longer treatment duration. This finding can inform policies for limiting opioid duration and dose to attenuate the risk of avoidable morbidity.
Highlights
Over the past 20 years, opioid prescribing and average prescription volumes continued to increase in the United States and Canada.[1,2] Opioids remain the main treatment for cancer pain, as recommended by the World Health Organization.[3]
Results from marginal structural Cox proportional hazards regression models showed more than a 2-fold increase in the risk of opioid-related adverse events associated with a cumulative use duration of more than 90 days compared with 1 to 30 days
A 3-fold risk increase was found with a mean daily dose higher than 90 milligram equivalent (MME) compared with 90 MME or lower
Summary
Over the past 20 years, opioid prescribing and average prescription volumes continued to increase in the United States and Canada.[1,2] Opioids remain the main treatment for cancer pain, as recommended by the World Health Organization.[3]. In the 2010s in North America, opioid use increased by nearly 100%,4 with acute pain being the most common indication.[5,6] These patterns in prescription opioids have been accompanied by higher rates of opioid-related morbidity and mortality.[4,7] Nonfatal opioid-related outcomes have been reported in older adults, even when the drugs were used as directed.[8,9] the long-term benefits are uncertain given that even short-term use may lead to greater predisposition to adverse events.[10] Longer trials have shown less pain relief with opioids, possibly because of pain tolerance or opioid-induced hyperalgesia.[11] This response may play a role in an escalation in the dose and potency of opioids, which subsequently may be associated with higher risk for adverse reactions. No opioid trial has followed up patients for longer than 6 months,[12] and most observational studies have examined only the association between the initial dose of opioid prescriptions and the duration of subsequent use.[13,14,15]
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