More than 1.9 million Americans are estimated to have a prescription opioid use disorder.1 A diagnosis of opioid use disorder is based on evidence of impaired control in avoiding use, social impairment, risky use, spending a significant time obtaining and using opioids, diminishing returns or tolerance to opioids and withdrawal symptoms that occur after stopping or reducing use.1 Treatment for opioid use disorder with bupenorphine therapy increased by 52% from 2012 to 2016.2 The misuse of opioids contributes to tens of thousands of deaths each year; in 2016 overdose deaths associated with opioids surpassed death from motor vehicle crashes.1,3 In the February 2018 issue of the APSF Newsletter, patient- and practice-based risk factors for opioid-induced ventilatory impairment (OIVI) were discussed.4 Identifying patient risk factors can be challenging, but there is a tool available to help anesthesia professionals and other perioperative clinicians identify patients with prior and current opioid use—prescription drug monitoring programs (PDMPs). This article reviews the relationship of prior opioid use to OIVI (including the concept of differential tolerance) and discusses how perioperative clinicians may utilize PDMPs to better identify patients in whom opioid tolerance may contribute to risk for OIVI.
|Table 1: Factors* included in Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (RIOSORD)15|
|Has the patient received care for any of the following health conditions in the past 6 months?
Does the patient consume any of the following?
Does the patient currently consume a prescribed opioid dose greater than or equal to 100 mg morphine equivalents per day on a regular basis?†
|*Each factor is associated with a different number of points or risk contribution in the RIOSORD.
†Reported in prescription drug monitoring programs.
RIOSORD was validated in both Veterans Health Administration (VHA)14 and non-VHA15 populations.
This table uses risk factors from the non-VHA validation study.
National trends in opioid prescription and opioid abuse
The acute rise in medical opioid prescriptions over the past two decades has driven an increasing prevalence of potentially opioid-tolerant and opioid-dependent individuals presenting for procedural care.3,5 Over the past ten years, there are mixed data regarding trends in prescription opioid use. National opioid prescription rates peaked in 2012, and there has been a slight decrease in the number of prescriptions and prescribed dosages since then. However, data show that prescribed duration of therapy slightly increased from 2006 to 2016; the percentage of opioid prescriptions for a greater than 30-day supply increased from 17.6% to 27.3% from 2006 to 2016.5 From 2013 to the present, the percentage of prescriptions for >30-day supply has decreased slightly, but not enough to offset the net 9% increase since 2006.5
Prevalence of preoperative opioid use
Rates of preoperative opioid use vary across surgical populations and are higher than in the general public. In Canada, 18.5% of patients presenting for ambulatory surgery were taking opioids preoperatively.6 A U.S. study of patients undergoing spinal fusion had significant variability in the use of preoperative chronic opioid therapy, with the majority (71.7%, 1,787/2,491) using some preoperative opioids (58.5% with long-term, 24.5% with episodic use, 5.3% with short-term use).7 These studies suggest geographic and procedure-related variation as well as methodological variation in defining chronic exposure.7,8
Preoperative opioid use and pain create significant challenges for the perioperative clinician. Preoperative opioid use predicts uncontrolled pain, increased costs, and poor satisfaction after orthopedic and general surgery.9-12 Retrospective studies suggest a correlation between chronic or preexisting opioid use with an increased likelihood of in-hospital respiratory depression requiring intervention and subsequent catastrophic injury.13 Research validating the Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (RIOSORD) suggests that opioid-tolerant patients are at significant risk for OIVI relative to patients without a history of opioid prescriptions and/or opioid tolerance.14,15 For example, a patient taking short-acting morphine in excess of 100-mg morphine equivalents per day would score 18 points on the 146-point RIOSORD scale, corresponding to a 29.8% probability of OIVI. If that same patient were to also have a substance use disorder (abuse or dependence), this risk jumps to 83.4%.15 Table 1 details the patient factors that contribute to the RIOSORD. Over the past decade, treatment for opioid misuse has increased, as have opioid prescribing rates.5 Given the risk for OIVI in this population, heightened provider awareness is paramount.
Relevance of Preoperative Opioid Use to OIVI
A recent review estimates that the incidence of postoperative OIVI is approximately 0.5%.16 In one study included in this review, opioid dependence or abuse contributes to OIVI with an odds ratio of 3.1 (95% CI:2.7-3.6), and previous substance abuse and chronic pain strongly predict opioid overdose.17,18 Preadmission substance abuse history, opioid exposure, and benzodiazepine exposure are major predictors in the aforementioned RIOSORD.14,15 While these retrospective studies are compelling, prospective studies are still needed to adequately characterize risk factors for OIVI.
Differential Tolerance: A Potential Mechanism for OIVI in This Population
It may be counterintuitive that opioid tolerance is associated with a higher risk of OIVI. However, tolerance of opioid-induced analgesia does not correlate with tolerance to OIVI.19,20 This may be related, in partto the finding that opioid-dependent patients may exhibit impaired hypercapnic ventilatory response even in the absence of acute opioid exposure.21 Continued opioid administration or dose escalation potentiates opioid-induced respiratory depression and sedation and may reflect differential tolerance.16 In closed-claims analysis, sedation was identified as a preceding symptom of OIVI in 62% of the events.4 Animal studies demonstrate differential tolerance develops within a matter of hours of initial opioid exposure suggesting a potential issue for opioid-naïve individuals.22
Lee et al. discuss the potential challenges of implementing a comprehensive OIVI risk factor checklist.4 Still, a standardized approach for identifying key patient factors, such as preoperative opioid use, may be useful in developing analgesic strategies that account for differential risk of OIVI. One such approach is PDMPs, which may aid clinicians in identifying those patients who either have previously used or are actively using opioids or benzodiazepines (another RIOSORD risk factor14), and who may be subsequently at higher risk for perioperative OIVI.
Prescription Drug Monitoring Programs (PDMPS)
PDMPs are state-administered monitoring programs that detail pharmacy-dispensed controlled substances shortly after the medication is released to the patient. Currently enacted in all 50 states, PDMPs (also called prescription monitoring programs—PMPs) provide a mechanism for identifying preoperative opioid and benzodiazepine use. Aberrant behaviors such as frequent opioid prescriptions from multiple prescribers suggest prescription misuse or overuse, and these patterns would be identifiable from PDMP records. Methadone dispensed by methadone clinics represents a blind spot, as it does not typically appear in PDMPs, but several states have proposed such inclusion to their state legislatures. Another reported pending addition to state-run PDMPs is the inclusion of Emergency Medical Services administration of naloxone.
Despite being run by states, there is a mechanism for sharing information across PDMPs. The PMP InterConnect® program of the National Association of Boards of Pharmacy (NABP) enables the 45 enrolled states to view prescribing data of the other NABP participant states.23 This InterConnect® system may allow for regulatory bodies and clinicians to identify those patients seeking care from multiple providers in states with separate PDMPs.
The Impact of PDMPS on Opioid Prescribing
PDMPs may reduce opioid overdose deaths and curb opioid prescribing rates via heightened clinician awareness of high-risk use including misuse or diversion. For instance, Florida saw a 25% reduction in oxycodone-caused mortality after PDMP implementation and other states have seen similar trends.24 Registration and use mandates as well as use exemptions are state-specific. Mandating health care professionals register for PDMP use significantly reduced opioid prescribing rates in adopting states, yet mandating clinicians use the PDMP for specific care scenarios did not create incremental reduction when combined with registration mandates or implemented independently.25 This suggests provider awareness of PDMPs via registration enables appropriate prescribing and suggests that use mandates may have too narrow of a scope to impact measurable changes in prescribing data.25
The clinical utility and impact of PDMP review by perioperative clinicians, however, is unknown and is a topic for future study. High-value utilization requires awareness of the PDMPs existence and capabilities, the current national trends in opioid use and misuse, and the clinical relevance of ongoing opioid use and addiction as factors in perioperative outcomes.
The PDMP: A Valuable Tool for Perioperative Care?
When the state of Illinois amended its controlled substance act requiring all clinicians to register to use the PDMP, relevance for many anesthesia professionals and intensivists was unclear, because both groups rarely prescribe post-hospital opioids. However, there are several reasons that PDMPs may be useful to perioperative clinicians.
First, PDMPs can be used to evaluate a patient’s preoperative or preadmission opioid exposure and potential for tolerance, misuse, or dependence. Preoperative clinics could use the PDMP to identify and guide candidates for preoperative opioid weaning or increased monitoring on the day of surgery. PDMPs also facilitate gathering information that may be unobtainable due to the emergent or urgent nature of presentation, as in a trauma setting.
Second, they may help in the creation of analgesic regimens for opioid-tolerant patients, who are at risk for severe, uncontrolled, and persistent pain. While recommended by multi-society postoperative pain guidelines, comprehensive preoperative evaluation of patient’s pain or psychiatric history varies substantially in practice,26 and PDMP review could constitute part of this history taking. Recognizing a pattern of frequent prescriptions from multiple providers or longstanding benzodiazepine prescriptions may suggest potential complexity in pain management,11,15,18 and might inform clinicians about the appropriate analgesic choices or the decision to obtain an early acute pain service consultation. Additionally, patients may not always be forthcoming due to fear of stigma, fear of legal consequences, or other concerns. PDMPs, while not comprehensive, provide information that may not be disclosed.
Third, discussion with patients of prescription data found in the PDMP may identify potential discrepancies or instances in which patients filled but did not take a prescription. Such instances can provide valuable and relevant information such as potential side effects, intolerance, or inefficacy when exposed to that medication previously reflecting occult pharmacogenomic issues or potential safety issues.
Finally, partial opioid receptor agonist/antagonists such as buprenorphine also appear in the PDMP. Identifying use of these agents facilitates broadened treatment planning and possible case deferral for possible cessation of such therapy prior to more painful surgery. Importantly, the presence of such medication suggests potential ongoing medication-assisted treatment for addiction, a comorbidity known to increase the risk of in-hospital respiratory failure.14
While far from a standard of care, the supplementary information offered by PDMPs may improve the quality of care provided to patients with preoperative opioid use, tolerance, or misuse. Moving forward, integration of PDMP data into electronic health records in a dynamic fashion (as opposed to the “flat” or read-only formatting most in use today) will enable the use of clinical decision support tools that may help in further mitigating risk of OIVI and improve analgesia for opioid-tolerant patients.
Prescription drug monitoring programs may offer a novel, supplementary data source for gathering important patient information for perioperative treatment planning and risk stratification. The multidisciplinary discussion of PDMP data preoperatively can guide preoperative patient preparation and education, perioperative pain care, postoperative and postdischarge monitoring and patient follow-up. The value of such utilization relies on provider recognition of the prevalence and significance of preoperative opioid use and misuse and the specific relationship between these factors and perioperative outcomes.
Dr. Dickerson is Director of the Acute Pain Service and Assistant Professor in the Department of Anesthesia & Critical Care at the University of Chicago.
Dr. Dickerson has no financial disclosures.
- Han B, Compton W, Blanco W, et al. Prescription opioid use, misuse, and use disorders in U.S. adults: 2015 national survey on drug use and health. Ann Int Med 2017;167:293-301.
- IMS Institute for Healthcare Informatics. Use of opioid recovery medications: recent evidence on state level buprenorphine use and payment types. 2016. https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/use-of-opioid-recovery-medications.pdf. Accessed 4/1/2018.
- Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15-4927, NSDUH Series H-50). 2015. https://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf. Accessed 4/1/2018.
- Lee L, Posner K, Domino K. We should focus on “when” as well as “whom” to monitor for postoperative opioid-induced ventilator impairment. APSF Newsletter 2018:32:59–60.
- Centers for Disease Control and Prevention. Annual surveillance report of drug-related risks and outcomes—United States, 2017. Surveillance Special Report 1. 2017. https://www.cdc.gov/drugoverdose/pdf/pubs/2017cdc-drug-surveillance-report.pdf. Accessed 4/1/2017.
- Wilson JL, Poulin PA, Sikorski R, et al. Opioid use among same-day surgery patients: prevalence, management and outcomes. Pain Res Manag 2015;20:300–304.
- Deyo RA, Hallvik SE, Hildebran C, et al. Use of prescription opioids before and after an operation for chronic pain (Lumbar Fusion Surgery). Pain 2018. Publish Ahead of Print: MAR 2018 DOI: 10.1097/j.pain.0000000000001202
- Jain N, Phillips FM, Weaver T, et al. Preoperative chronic opioid therapy: a risk factor for complications, readmission, continued opioid use and increased costs after one- and two-level posterior lumbar fusion. Spine (Phila Pa 1976). 2018 Mar 20. doi: 10.1097/BRS.0000000000002609. [Epub ahead of print].
- Zywiel MG, Stroh DA, Lee SY, et al. Chronic opioid use prior to total knee arthroplasty. J Bone Joint Surg Am 2011;93:1988–1993.
- Cron DC, Englesbe MJ, Bolton CJ, et al. Preoperative opioid use is independently associated with increased costs and worse outcomes after major abdominal surgery. Ann Surg 2017;265:695–701.
- Ip HY, Abrishami A, Peng PW, et al. Predictors of postoperative pain and analgesic consumption: a qualitative systematic review. Anesthesiology 2009;111: 657–677.
- Schwenkglenks M, Gerbershagen HJ, Taylor RS, et al. Correlates of satisfaction with pain treatment in the acute postoperative period: results from the international PAIN OUT registry. Pain 2014;155:1401–1411.
- Lee LA, Caplan RA, Stephens LS, et al. Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology 2015;122:659–665.
- Zedler B, Xie L, Wang L, et al. Development of a risk index for serious prescription opioid-induced respiratory depression or overdose in veterans’ health administration patients. Pain Medicine 2015;16:1566–1579.
- Zedler BK, Saunders WB, Joyce AR, et al. Validation of a screening risk index for serious prescription opioid-induced respiratory depression or overdose in a US Commercial Health Plan Claims Database. Pain Medicine 2018;19:68–78.
- Gupta K, Prasad A, Nagappa M, et al. Risk factors for opioid-induced respiratory depression and failure to rescue: a review. Curr Opin Anaesthesiol 2018;31:110–119.
- Menendez ME, Ring D, Bateman BT. Preoperative opioid misuse is associated with increased morbidity and mortality after elective orthopaedic surgery. Clin Orthop Relat Res 2015;473:2402–2412.
- Cauley CE, Anderson G, Haynes AB, et al. Predictors of in-hospital postoperative opioid overdose after major elective operations: a nationally representative cohort study. Ann Surg 2017;265:702–708.
- Hayhurst CJ, Durieux ME. Differential opioid tolerance and opioid-induced hyperalgesia: a clinical reality. Anesthesiology 2016;124:483–488.
- Athanasos P, Smith CS, White JM, et al. Methadone maintenance patients are cross-tolerant to the antinociceptive effects of very high plasma morphine concentrations. Pain 2006;120:267–275.
- Teichtahl H, Wang D, Cunnington D, et al. Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients. Chest 2005;128:1339–1347.
- Ling GS, Paul D, Simantov R, et al. Differential development of acute tolerance to analgesia, respiratory depression, gastrointestinal transit and hormone release in a morphine infusion model. Life Sci 1989; 45:1627–36.
- NABP PMP InterConnect: The Only National Network of State-Based PMPs. https://nabp.pharmacy/initiatives/pmp-interconnect/. Accessed 4/4/2018.
- Delcher C, Wagenaar AC, Goldberger BA, et al. Abrupt decline in oxycodone-caused mortality after implementation of Florida’s Prescription Drug Monitoring Program. Drug Alcohol Depend 2015;150:63–68.
- Wen H, Schackman BR, Aden B, et al. States with prescription drug monitoring mandates saw a reduction in opioids prescribed to medicaid enrollees. Health Aff (Millwood). 2017;36:733–741.
- Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. The Journal of Pain 2016;17:131–157.