Preoperative Opioid Use and Mortality After Minor Outpatient Surgery | Addiction Medicine | JAMA Surgery | JAMA Network
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Figure.  Adjusted 90-Day Mortality by Preoperative Opioid Use
Adjusted 90-Day Mortality by Preoperative Opioid Use

Procedures included varicose vein removal, hemorrhoidectomy, laparoscopic cholecystectomy, transurethral prostate surgery, thyroidectomy, parathyroidectomy, carpal tunnel release, umbilical hernia repair, and inguinal hernia repair. Mortality was adjusted for age, sex, race, Medicaid eligibility, type of surgery, Charlson Comorbidity Index, history of tobacco use, mental health disorders, pain disorders, hospitalization in prior year, stay in skilled nursing facility in prior year, concurrent fill of benzodiazepine, and frailty index.

Table.  Clusters by Preoperative Opioid Use
Clusters by Preoperative Opioid Use
1.
Yoshikawa  A, Ramirez  G, Smith  ML,  et al.  Opioid use and the risk of falls, fall injuries and fractures among older adults: a systematic review and meta-analysis.   J Gerontol A Biol Sci Med Sci. Published online February 4, 2020. doi:10.1093/gerona/glaa038Google Scholar
2.
Tang  R, Santosa  KB, Vu  JV,  et al.  Preoperative opioid use and readmissions following surgery.   Ann Surg. Published online March 13, 2020. doi:10.1097/SLA.0000000000003827PubMedGoogle Scholar
3.
Vu  JV, Cron  DC, Lee  JS,  et al.  Classifying preoperative opioid use for surgical care.   Ann Surg. 2020;271(6):1080-1086.PubMedGoogle ScholarCrossref
4.
Orkaby  AR, Nussbaum  L, Ho  YL,  et al.  The burden of frailty among U.S. veterans and its association with mortality, 2002-2012.   J Gerontol A Biol Sci Med Sci. 2019;74(8):1257-1264. doi:10.1093/gerona/gly232PubMedGoogle ScholarCrossref
5.
Ray  WA, Chung  CP, Murray  KT, Hall  K, Stein  CM.  Prescription of long-acting opioids and mortality in patients with chronic noncancer pain.   JAMA. 2016;315(22):2415-2423. doi:10.1001/jama.2016.7789PubMedGoogle ScholarCrossref
6.
Hilliard  PE, Waljee  J, Moser  S,  et al.  Prevalence of preoperative opioid use and characteristics associated with opioid use among patients presenting for surgery.   JAMA Surg. 2018;153(10):929-937. doi:10.1001/jamasurg.2018.2102PubMedGoogle ScholarCrossref
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    1 Comment for this article
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    Premature to take action (to recommend weaning opioids) based on this study
    Richard Saitz, MD, MPH | Boston University School of Public Health and Boston Medical Center
    The association between opioid prescription fills and 90-day postoperative mortality certainly is worth understanding--it is a hypothesis generating study.

    But it seems more likely than not, that the association is a result of confounding by indication. Adjusting for comorbidity, surgery type and frailty is not enough to outweigh the likelihood that people prescribed opioids are very different from those who are not, in ways likely associated with mortality. And the modest size odds ratio confidence intervals (based on small numerators) overlap with no convincing trend. We do not know causes of death—were they opioid-related in some way? The
    data are inadequate to assume the association is causal.

    Without knowing indications, risks, and benefits of preoperative prescription fills, what if anything the surgery had to do with presumed opioid-related mortality, and with the other limitations of the study, it is premature to recommend opioid “weaning” prior to surgery, or any other action, other than judicious prescribing for appropriate indications with appropriate monitoring.
    CONFLICT OF INTEREST: Dr Saitz reports grants from National Institutes of Health; non-financial support from Alkermes, grants from National Institute on Alcohol Abuse and Alcoholism, grants from National Institute on Drug Abuse, grants from Philadelphia College of Osteopathic Medicine, grants from Burroughs Wellcome Fund, personal fees from American Society of Addiction Medicine, American Medical Association, Checkup & Choices, National Council on Behavioral Healthcare, Kasier Permanente, UpToDate/Wolters Kluwer, Yale University, National Committee on Quality Assurance, University of Oregon, Oregon Health Sciences University, RAND Corporation, Leed Management Consulting/Harvard Medical School, Partners, personal fees from Beth Israel/Deaconess Hospital, American Academy of Addiction Psychiatry, Group Health Cooperative, travel support from International Network on Brief Interventions for Alcohol and Other Drugs (INEBRIA), travel funds from Systembolaget, personal fees from Smart Recovery, personal fees from Karolinska Institutet, from Institute for Research and Training in the Addictions, Medical Malpractice Expert Witness, Charles University, Prague, Brandeis University, and Massachusetts Medical Society outside the submitted work; and President, International Society of Addiction Journal Editors; research consulting to ABT Corporation (not remunerated), Physician at Boston Medical Center, Boston, MA. Editor of a book published by Springer, Editor in Chief Journal of Addiction Medicine, Editorial Board of J Addictive Diseases and Addiction Science and Clinical Practice and Substance Abuse, and associate Editor, JAMA.
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    Research Letter
    October 21, 2020

    Preoperative Opioid Use and Mortality After Minor Outpatient Surgery

    Author Affiliations
    • 1Section of Plastic Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor
    • 2Michigan Opioid Prescribing Engagement Network, Ann Arbor
    • 3Department of Biomedical Engineering, University of Utah, Bountiful
    • 4Division of Pain Medicine, Department of Anesthesia, University of Michigan Health System, Ann Arbor
    • 5Section of Transplantation, Department of Surgery, University of Michigan Health System, Ann Arbor
    JAMA Surg. 2020;155(12):1169-1171. doi:10.1001/jamasurg.2020.3623

    Among older patients, opioid analgesics are associated with falls, fractures, and respiratory complications.1 Although the effect of preoperative opioid exposure on postoperative events has been described,2 little is known about its effect on mortality. As the proportion of older individuals undergoing surgery is rising, we sought to evaluate the risk of preoperative opioid exposure on all-cause mortality after outpatient surgery.

    Methods

    Using a 20% national sample of Medicare beneficiaries, we examined individuals 65 years or older who underwent outpatient surgical procedures between January 1, 2009, and September 30, 2015, with continuous enrollment in Medicare Parts A, B, and D at least 12 months prior to and 3 days after their discharge date. This study was deemed exempt by the institutional review board at the University of Michigan.

    Our primary outcome was 90-day mortality after surgery. We defined preoperative opioid use as pharmaceutical fills in the year prior to surgery including dose, duration, proximity to surgical date, and continuity of fills. We classified preoperative opioid use as naive, low, medium, and high (Table).3 We used logistic regression to examine all-cause mortality and preoperative opioid use adjusting for medical comorbidities, surgery type, and frailty.4 Statistical analyses were performed using Stata version 15.1 (StataCorp), SAS version 9.4 (SAS Institute), and R version 4.0.1 (R Foundation for Statistical Computing). Statistical significance was set at 2-tailed P value less than .05. Analysis began September 2019 and ended March 2020.

    Results

    In total, there were 99 125 patients included for analysis. Of these, 54 582 (55.06%) were male. Overall 90-day postoperative mortality was 0.48% (471 of 99 125). Preoperative opioid use was correlated with an increased mortality within 90 days after surgery (Figure), and patients with high preoperative opioid exposure were more likely to die within 90 days after outpatient surgery compared with opioid-naive patients (adjusted odds ratio, 1.68; 95% CI, 1.16-2.44), even after controlling for type of surgery. Medium preoperative opioid users also had higher rates of 90-day mortality compared with opioid-naive patients (adjusted odds ratio, 1.30; 95% CI, 1.01-1.67). Mortality did not differ between opioid-naive patients and patients with low preoperative opioid exposure.

    Discussion

    Opioid analgesics are effective in managing acute pain but are associated with important risks, particularly among older adults.5 Among Medicare beneficiaries, we observed higher mortality among individuals undergoing outpatient surgery who had greater preoperative exposure.

    While guidelines exist for long-term opioid therapy, guidelines for the management of acute pain have only recently emerged, and few consider the potential risks of preoperative opioid exposure. Postoperative prescribing guidelines for common surgical procedures released by professional societies have largely focused on pain management among opioid-naive patients, with less direction regarding preoperative opioid exposures. Nonetheless, current opioid use is correlated with higher perioperative risk,6 and future studies that examine the mechanisms by which opioids mediate postoperative outcomes are necessary to tailor preoperative screening.

    Our study is limited, and we cannot capture opioid use outside of claims. Furthermore, there are likely unmeasured factors that contribute to mortality that we cannot account for. However, our findings highlight the need to address preoperative opioid exposure to ensure a safe postoperative recovery. Patients who use opioids preoperatively may not only require higher doses of opioids for postoperative pain control because of tolerance, but are also more vulnerable to opioid-related adverse events, such as respiratory complications, readmissions, and mortality.2 Going forward, for patients with high opioid exposure, opioid weaning prior to surgery could optimize postoperative care. Other strategies to mitigate opioid-related risk could include coprescribing with naloxone, avoidance of benzodiazepines, delaying discretionary procedures, and encouraging the use of opioid alternatives for pain management. Implementation of these strategies could help reduce the risk of mortality after outpatient surgery, improving the safety of surgical care.

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    Article Information

    Corresponding Author: Jennifer F. Waljee, MD, MPH, MS, Section of Plastic Surgery, Department of Surgery, University of Michigan Health System, 1500 E Medical Center Dr, Ann Arbor, MI 48109 (filip@med.umich.edu).

    Accepted for Publication: July 11, 2020.

    Published Online: October 21, 2020. doi:10.1001/jamasurg.2020.3623

    Author Contributions: Dr Waljee had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Santosa, Lai, Oliver, Brummett, Englesbe, Waljee.

    Acquisition, analysis, or interpretation of data: Santosa, Lai, Oliver, Hu, Brummett, Waljee.

    Drafting of the manuscript: Santosa, Lai, Oliver, Waljee.

    Critical revision of the manuscript for important intellectual content: Lai, Hu, Brummett, Englesbe, Waljee.

    Statistical analysis: Lai, Hu.

    Obtained funding: Brummett, Waljee.

    Administrative, technical, or material support: Oliver, Brummett.

    Supervision: Santosa, Brummett, Englesbe, Waljee.

    Conflict of Interest Disclosures: Dr Brummett reports personal fees from Heron Therapeutics and Alosa Health for consulting outside the submitted work. No other disclosures were reported.

    Funding/Support: This study was supported by the National Institutes of Health, National Institute on Drug Abuse (grant R01DA042859) awarded to Drs Waljee and Brummett.

    Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Disclaimer: The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

    References
    1.
    Yoshikawa  A, Ramirez  G, Smith  ML,  et al.  Opioid use and the risk of falls, fall injuries and fractures among older adults: a systematic review and meta-analysis.   J Gerontol A Biol Sci Med Sci. Published online February 4, 2020. doi:10.1093/gerona/glaa038Google Scholar
    2.
    Tang  R, Santosa  KB, Vu  JV,  et al.  Preoperative opioid use and readmissions following surgery.   Ann Surg. Published online March 13, 2020. doi:10.1097/SLA.0000000000003827PubMedGoogle Scholar
    3.
    Vu  JV, Cron  DC, Lee  JS,  et al.  Classifying preoperative opioid use for surgical care.   Ann Surg. 2020;271(6):1080-1086.PubMedGoogle ScholarCrossref
    4.
    Orkaby  AR, Nussbaum  L, Ho  YL,  et al.  The burden of frailty among U.S. veterans and its association with mortality, 2002-2012.   J Gerontol A Biol Sci Med Sci. 2019;74(8):1257-1264. doi:10.1093/gerona/gly232PubMedGoogle ScholarCrossref
    5.
    Ray  WA, Chung  CP, Murray  KT, Hall  K, Stein  CM.  Prescription of long-acting opioids and mortality in patients with chronic noncancer pain.   JAMA. 2016;315(22):2415-2423. doi:10.1001/jama.2016.7789PubMedGoogle ScholarCrossref
    6.
    Hilliard  PE, Waljee  J, Moser  S,  et al.  Prevalence of preoperative opioid use and characteristics associated with opioid use among patients presenting for surgery.   JAMA Surg. 2018;153(10):929-937. doi:10.1001/jamasurg.2018.2102PubMedGoogle ScholarCrossref
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