While patients may be newly exposed to opioids during medical and surgical hospitalization and the prescription of opioids at discharge is common,1-5 prescribers of opioids at discharge may not intend to initiate long-term opioid (LTO) use. By understanding the frequency of progression to LTO use, hospitalists can better balance postdischarge pain treatment and the risk for unintended LTO initiation.
Estimates of LTO use rates following hospital discharge in selected populations1,2,4-6 have varied depending on the population studied and the method of defining LTO use.7 Rates of LTO use following incident opioid prescription have not been directly compared at medical versus surgical discharge or compared with initiation in the ambulatory setting. We present the rates of LTO use following incident opioid exposure at surgical discharge and medical discharge and identify the factors associated with LTO use following surgical and medical discharge.
Veterans Health Administration (VHA) data were obtained through the Austin Information Technology Center for fiscal years (FYs) 2003 through 2012 (Austin, Texas). Decision support system national data extracts were used to identify prescription-dispensing events, and inpatient and outpatient medical SAS data sets were used to identify diagnostic codes. The study was approved by the University of Iowa Institutional Review Board and the Iowa City Veterans Affairs (VA) Health Care System Research and Development Committee.
We included all patients with an outpatient opioid prescription during FY 2011 that was preceded by a 1-year opioid-free period.7 Patients with broadly accepted indications for LTO use (eg, metastatic cancer, palliative care, or opioid-dependence treatment) were excluded.7
We included all outpatient prescription fills for noninjectable dosage forms of butorphanol, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxycodone, oxymorphone, pentazocine, and tramadol. Consistent with the Centers for Disease Control and Prevention and VA/Department of Defense guidelines, LTO use was defined conceptually as regular use for >90 days. Operationalizing this definition to pharmacy refill data was established by using a cabinet supply methodology,7 which allows for the construction of episodes of continuous medication therapy by estimating the medication supply available to a patient for each day during a defined period based on the pattern of observed refills. LTO use was defined as an episode of continuous opioid supply for >90 days and beginning within 30 days of the initial prescription. While some studies have defined LTO use based on onset within 1 year following surgery,5 the requirement for onset within 30 days of initiation was applied to more strongly tie the association of developing LTO use with the discharge event and minimize various forms of bias that are introduced with extended follow-up periods.
Patients were classified as being medical discharges, surgical discharges, or outpatient initiators. Patients with an opioid index date within 2 days following discharge were designated based on discharge bed section; additionally, if patients had a surgical bed section during hospitalization, they were assigned as surgical discharges. Demographic, diagnosis, and medication exposure variables that were previously associated with LTO use were selected.8,9 Substance use disorder, chronic pain, anxiety disorder, and depressive disorder were based on International Classification of Diseases, 9th Revision (ICD-9) codes in the preceding year. The use of concurrent benzodiazepines, skeletal muscle relaxants, and antidepressants were determined at opioid initiation.10 Rural or urban residence was assigned by using the Rural-Urban Commuting Area Codes system and mapped with the zip code of a veteran’s residence.11
Bivariate and multivariable relationships were determined by using logistic regression. The multivariable model considered all pairwise interaction terms between inpatient service (surgery versus medicine) and each of the variables in the model. Statistically significant interaction terms (P < .05) were retained, and all others were omitted from the final model. The main effects for variables that were involved in a significant interaction term were not reported in the final multivariable model; instead, we created fully specified multivariable models for surgery service and medicine service and reported odds ratios (ORs) for the main effects. All analyses were conducted by using SAS version 9.4 (SAS Institute Inc, Cary, North Carolina).
Days’ supply was associated with LTO use in a dose-dependent fashion relative to the reference category of ≤7 days: OR of 1.24 (95% CI, 1.12-1.37) for 8 to 14 days; OR of 1.56 (95% CI, 1.39-1.76) for 15 to 29 days; and OR of 2.59 (95% CI, 2.35-2.86) for 30 days (Table 2). LTO risk was higher among patients with an estimated dose of ≥15 morphine equivalents per day (MED) compared with those with doses of <15 equivalents (OR = 1.11; 95% CI, 1.02-1.21); patients who received >45 MED were at the greatest risk (OR = 1.70; 95% CI, 1.49-1.94).
The observation that subsequent LTO use occurs more frequently in discharged medical patients than surgical patients is consistent with the findings of Calcaterra et al.1 that among patients with no surgery versus surgery during hospitalization, opioid receipt at discharge resulted in a higher adjusted OR (7.24 for no surgery versus 3.40 for surgery) for chronic opioid use at 1 year. One explanation for this finding may be an artifact of cohort selection in the study design: patients with prior opioid use are excluded from the cohort, and prior use may be more common among surgical patients presenting for elective inpatient surgery for painful conditions. Previous work suggests that opioid use preoperatively is a robust predictor of postoperative use, and rates of LTO use are low among patients without preoperative opioid exposure.6
Demographic characteristics associated with persistent opioid receipt were similar to those previously reported.5,8,9 The inclusion of medication classes indicated in the treatment of mental health or pain conditions (ie, antidepressants, benzodiazepines, muscle relaxants, and nonopioid analgesics) resulted in diagnoses based on ICD-9 codes being no longer associated with LTO use. Severity or activity of illness, preferences regarding pharmacologic or nonpharmacologic treatment and undiagnosed or undocumented pain-comorbid conditions may all contribute to this finding. Future work studying opioid-related outcomes should include variables that reflect pharmacologic management of comorbid diagnoses in the cohort development or analytic design.
The strongest risk factors were potentially modifiable: days’ supply, dose, and concurrent medications. The measures of opioid quantity supplied are associated with subsequent ongoing use and are consistent with recent work based on prescription drug–monitoring data in a single state14 and in a nationally representative sample.15 That this relationship persists following hospital discharge, a scenario in which LTO use is unlikely to be initiated by a provider (who would be expected to subsequently titrate or monitor therapy), further supports the potential to curtail unintended LTO use through judicious early prescribing decisions.
We assessed only opioids that were supplied through a VA pharmacy, which may lead to the misclassification of patients as opioid naive for inclusion and an underestimation of the rate of opioid use following discharge. It is possible that differences in the rates of non-VA pharmacy use differ in medical and surgical populations in a nonrandom way. This study was performed in a large, integrated health system and may not be generalizable outside the VA system, where more discontinuities between hospital and ambulatory care may exist.
The initiation of LTO use at discharge is more common in veterans who are discharged from medical than surgical hospitalizations, likely reflecting differences in the patient population, pain conditions, and discharge prescribing decisions. While patient characteristics are associated with LTO use, the strongest associations are with increasing index dose and days’ supply; both represent potentially modifiable prescriber behaviors. These findings support policy changes and other efforts to minimize dose and days supplied when short-term use is intended as a means to address the current opioid epidemic.
The work reported here was supported by the Department of Veterans Affairs Office of Academic Affiliations and Office of Research and Development (Dr. Mosher and Dr. Hofmeyer), and Health Services Research and Development Service (HSR&D) through the Comprehensive Access and Delivery Research and Evaluation Center (CIN 13-412) and a Career Development Award (CDA 10-017; Dr. Lund).
The authors report no conflict of interest in regard to this study. The authors had full access to and take full responsibility for the integrity of the data. All analyses were conducted by using SAS version 9.2 (SAS Institute Inc, Cary, NC). This manuscript is not under review elsewhere, and there is no prior publication of the manuscript contents. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The study was approved by the University of Iowa Institutional Review Board and the Iowa City Healthcare System Research and Development Committee.