Perioperative Opioids, the Opioid Crisis, and the Anesthesiologist

Daniel B. Larach, M.D., M.S.T.R., M.A.; Jennifer M. Hah, M.D., M.S.; Chad M. Brummett, M.D

Disclosures

Anesthesiology. 2022;136(4):594-608. 

In This Article

Postoperative Considerations

Postoperative Order Sets and "Automatic" Opioid Administration

Evidence exists that in-hospital opioid use is highly associated with postdischarge opioid use.[109,110] In addition, elimination of standing orders for opioids from post–cesarean section order sets has been shown to decrease postoperative opioid consumption and discharge opioid prescribing.[111] Further research is warranted into whether changes in postanesthesia care unit opioid order sets can have a similar influence on postoperative opioid consumption and persistent use in other cohorts. It has been posited that limiting intraoperative opioids may lead to increased postoperative opioid use, which would be counterproductive.[106] However, changes in postanesthesia care unit opioid administration in concert with changes in hospital ward and discharge opioid prescribing by surgical services represent a more attractive opportunity for anesthesiologists to improve short- and long-term opioid outcomes when compared with intraoperative opioid elimination.

Educational and Behavioral Interventions

Educational and behavioral interventions initiated or coordinated by anesthesiologists or other members of the perioperative care team provide an avenue to curb postoperative opioid use.[112] For example, carpal tunnel surgery patients who reviewed a one-page sheet that (1) recommended trialing nonopioid therapy before using prescribed opioids, (2) assessed opioid abuse risk factors and current opioid prescriptions, (3) provided education on the anticipated duration of opioid consumption after surgery, and (4) set expectations that the lowest opioid dose would be prescribed exhibited significantly decreased opioid consumption (mean 1.4 pills vs. 4.2 pills) over the first 3 postoperative days compared with a group that did not receive the educational intervention, without a significant difference in pain scores.[113] In another trial, arthroscopic rotator cuff repair patients randomized to an intervention group watched a 2-min narrated video and read a handout detailing the risks of opioid overuse and abuse. Overall, a statistically significant 42% reduction in opioid consumption was reported in the 3 months after surgery with no differences in pain.[114] However, a third randomized trial in which total hip or knee arthroplasty patients at risk for opioid-related harms were provided brochures detailing expectations for opioid use and pain control after surgery, rationale for opioid use after surgery, postoperative opioid tapering expectations, and opioid-related adverse effects found no significant reduction in the amount of opioids dispensed in the 90 days after surgery.[115] While these data are not conclusive, anesthesiologists may consider formal or informal discussions related to postoperative opioid use in the preoperative holding area.

Behavioral interventions can be delivered to guide postoperative opioid tapering. In a randomized trial of motivational interviewing and guided opioid tapering support compared to usual care alone administered to patients who had undergone total hip or knee arthroplasty, patients randomized to the intervention were instructed to decrease their total daily opioid dose by 25% every 7 days while monitoring for pain and adverse effects.[116] Patients randomized to a taper experienced a 62% increase in the incidence of return to baseline opioid use after surgery (hazard ratio, 1.62; 95% CI, 1.06 to 2.46; P = 0.03), and a 53% increase in the incidence of complete postoperative opioid cessation (hazard ratio, 1.57; 95% CI, 1.01 to 2.44; P = 0.05) with no adverse effects on the duration of pain or patient-reported recovery. The intervention was delivered via phone calls weekly from 2 to 7 weeks postoperatively and then monthly up to 1 year until patient-reported opioid cessation. However, patients receiving the motivational interviewing and guided tapering support intervention required an average of only three calls, demonstrating the feasibility of future scale-up of this intervention. Future research on interventions to promote postoperative opioid cessation and opioid tapering among high-risk patients is warranted as these patients are less likely to fit into the framework of conservative opioid prescribing. The increase in use and reimbursement of telehealth amid the COVID-19 pandemic further facilitates such access for transitional pain services.[117,118]

Behavioral interventions provide a promising avenue to limit postoperative opioid use and encourage postoperative opioid cessation. In a small randomized controlled clinical trial, patients assigned to a digital behavioral health intervention stopped opioids 5 days sooner without differences in self-reported pain when compared to a digital health information control group.[93] However, further research is needed to develop interventions specific to those at highest risk, including those with anxiety, chronic pain, or opioid tolerance. Web- and smartphone-based interventions are attractive, as they address some of the cost and access barriers to in-person behavioral treatments.

Perioperative Management of Patients With Opioid use Disorder

The anesthesiologist's intersection with the opioid crisis is most apparent when encountering a patient with a history of opioid use disorder. Opioid use disorder results in substantial morbidity and mortality, including opioid-related overdoses.[119] It is associated with multiple comorbidities including psychiatric diagnoses, human immunodeficiency virus, and hepatitis C.[120] The prevalence of this condition is estimated to be anywhere from 0.8 to 4.6% nationwide.[20,21] Given the rapidly changing landscape of treatment to address the opioid crisis, anesthesiologists should be aware of the various U.S. Food and Drug Administration (Silver Spring, Maryland)–approved opioid use disorder treatment formulations and considerations for perioperative opioid management. Currently, three medications (buprenorphine, methadone, and naltrexone) are Food and Drug Administration–approved to treat opioid use disorder in various formulations. All these treatments have demonstrated reductions in illicit opioid use and mortality, yet most patients with opioid use disorder do not receive any of them.[121–128]

Acute pain management in patients receiving opioid use disorder treatment can be particularly challenging given the heightened postoperative opioid requirements for pain control. However, rigorous research to inform evidence-based management is lacking, with most recommendations derived from expert opinion and case reports.[129–131] Based on observational studies, continuation of buprenorphine and methadone opioid use disorder treatment after surgery may reduce supplemental opioid needs.[129] Further, suboptimal pain management in patients receiving methadone may trigger disengagement from care and serious downstream effects of possible relapse, overdose, or suicide.[129,130]

Buprenorphine is a partial μ-opioid receptor agonist and antagonist at the κ- and δ-opioid receptors. Given its high affinity for the μ receptor, buprenorphine competitively displaces other μ receptor agonists and can reduce opioid binding by 80 to 95% at clinical dose ranges.[132] Given these considerations, older algorithms recommended the discontinuation of buprenorphine before major surgery to allow for adequate analgesia from traditional μ agonists. However, preoperative discontinuation of buprenorphine may result in increased pain and higher opioid requirements.[130] Adequate pain control has been described with concomitant use of full opioid agonists with continuation of buprenorphine treatment. Rather than complete discontinuation, buprenorphine doses may be tapered to a lower dose so that analgesia can be achieved with a full opioid agonist while maintaining treatment to minimize the risks of relapse. A potential target for buprenorphine dose reductions has been suggested as 8 to 12 mg daily of the sublingual tablet.[132] Although patients receiving methadone for opioid use disorder treatment have not demonstrated an increased risk of relapse with concomitant use of other opioid analgesics, the same has not been demonstrated among patients receiving buprenorphine, and continued surveillance after surgery is warranted.[132] In general, buprenorphine can be restarted 12 to 24 h after the last dose of a short-acting opioid or 24 to 48 h after the last dose of a long-acting opioid if it had been discontinued.

Methadone, a full μ-opioid receptor agonist with N-methyl-D-aspartate antagonist and serotonin and norepinephrine reuptake inhibition properties, is administered as a daily oral medication by certified specialty clinics.[133–135] When prescribed for opioid use disorder treatment, patients receiving methadone are less likely to experience euphoria from heroin abuse.[130] Surgical patients can be instructed to take their usual methadone dose on the day of their scheduled procedure. Additional immediate-release opioids may be prescribed for the acute pain. Given the heightened risk of relapse, discontinuation of methadone is not generally recommended.[130]

Naltrexone is approved by the U.S. Food and Drug Administration for the treatment of both opioid use disorder and alcohol use disorder and acts as a competitive opioid antagonist at the μ-opioid receptor.[130] The oral formulation was found to be no more effective than placebo but continues to be prescribed more frequently than the injectable formulation. This medication blocks the euphoria, analgesia, and sedation from opioid agonists. Some authors have suggested discontinuing naltrexone preoperatively with the last dose 2 to 3 days before surgery for the oral formulation, and 30 days before surgery for the injectable extended release formulation.[130] Before restarting naltrexone after surgery, patients should not be taking opioid agonists for at least 7 to 10 days, as this will precipitate acute opioid withdrawal if administered to a patient actively using opioids. In the event that preoperative naltrexone discontinuation is not feasible (e.g., emergency surgery), nonopioid analgesics, nonpharmacologic treatment, and regional anesthetic techniques can be considered.[130] For surgeries in which opioids will not be required or can be avoided for perioperative care, there is no need to alter the naltrexone management. Of note, new longer-acting formulations of naltrexone are being trialed that would make such care coordination nearly impossible. Close communication with the patient's addiction specialist and surgeon will be required in such a situation.

Regardless of the perioperative management strategy chosen for opioid use disorder treatment, all patients receiving such therapy can be considered for perioperative multimodal analgesia, regional anesthesia techniques, and specialist referrals when needed (addiction medicine, psychiatry, and pain medicine). The patient's addiction provider should be engaged in all decision-making, and patients and their families must understand the plan and be engaged in decision-making. Discharge planning should include a clear transition plan back to the maintenance treatment.

Influencing Surgeon Prescribing Practices

Opioids. Anesthesiologists can serve as a resource for surgical colleagues regarding postdischarge prescribing. Multiple studies have demonstrated that the amount of opioid prescribed can be greatly reduced from traditional norms without adversely impacting patient-reported pain, satisfaction, or refill requests.[54,56,109] While early analyses show that policy interventions have not led to meaningful decreases in opioid prescriptions,[136,137] the implementation of surgery-specific prescribing recommendations offers more promise.[55,138,139] To facilitate this, opioid prescribing guidelines for many common surgeries are available at www.opioidprescribing.info, along with specific counseling recommendations such as setting expectations; encouraging nonopioid pain medication use; and describing adverse effects, appropriate versus inappropriate use, and safe disposal.[140] These evidence-based prescribing recommendations from the Opioid Prescribing Engagement Network at the University of Michigan (Ann Arbor, Michigan) were created from patient-reported outcomes from health systems throughout the state of Michigan. Implementation of these recommendations in a cohort of more than 11,000 patients across 43 centers led to a significant decrease in postdischarge opioid prescribing without increases in pain or reduction in satisfaction.[55] These recommendations are updated approximately three times per year based on new data; postsurgical prescribing recommendations are also available from other large academic centers (e.g., Johns Hopkins Medicine [Baltimore, Maryland] and the Mayo Clinic [Rochester, Minnesota]).[141,142] Ensuring that our surgical colleagues are aware of prescribing recommendations should be considered part of anesthesiologists' roles as complete perioperative physicians. As noted in the section "Excess Opioid Prescribing," postsurgical prescribing by anesthesiologists is the norm in several other countries.

Naloxone. Naloxone, an opioid receptor antagonist, has been shown to be effective in treating opioid overdose when administered in intravenous, intramuscular, and intranasal forms.[143] Naloxone prescribing increased nationally between 2014 to 2017, but only approximately 2% of patients with risk factors for opioid-related overdose received a naloxone prescription.[144] While these data were not specific to perioperative care, one can assume the rates of postoperative prescribing of naloxone were the same or lower. Costs between the different formulations and delivery systems vary widely.[145] Most recommend intranasal formulations of naloxone given higher patient acceptance compared to injectable formulations. Anesthesiologists should assist in identifying patients with risk factors for opioid overdose such as obesity and co-prescribed benzodiazepines.[146,147] Given that evaluation for these risk factors is a routine part of the preoperative evaluation, anesthesiologists are well placed to identify patients who would benefit from naloxone prescription and communicate this to surgeons.

Conclusions

Anesthesiologists have a unique opportunity to show value in the healthcare system by positively impacting the devastating opioid epidemic. A wide variety of surgeries have been linked with excess opioid prescribing and the development of new persistent postoperative opioid use. Although continued research is required to clarify the relationship between perioperative opioid use and concrete opioid-related harms, there are several practical steps anesthesiologists can take to improved acute and chronic postoperative outcomes. Furthermore, there is a pressing need to develop a personalized approach to perioperative opioid-related risk stratification, management, and the prevention of persistent postsurgical pain.

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