The Role of Opioids in Spine Surgery

Even during this global pandemic, we have continued to prioritize addressing the opioid crisis,” began FDA Commissioner Stephen M. Hahn, M.D. after the FDA announced a new rule requiring labeling on opioid medication to recommend that healthcare professionals have a discussion with patients about the availability of naloxone to reverse the effects of an opioid overdose. Hahn continued, “Today’s action can help further raise awareness about this potentially life-saving treatment for individuals that may be at greater risk of an overdose and those in the community most likely to observe an overdose.”

“While most surgical specialties use opioids as part of post-operative pain management, orthopedic surgeons have historically prescribed opioids at a higher rate than other specialists. A 2020 study published in Surgery Open Science (“The opioid prescribing practices of surgeons: A comprehensive review of the 2015 claims to Medicare Part D”) investigated the opioid prescribing rates among specialties using 2015 Medicare Part D data. The researchers found that 48.6% of prescriptions written by orthopedic surgeons were for opioids. The rate of opioid vs other drug prescriptions was significantly higher for orthopedic surgeons than nearly all other surgical specialties.

As Hahn mentioned, steps to control the opioid crisis cannot relent due to concerns of the COVID-19 pandemic. Research and physician education are important parts of the effort to change prescription writing behavior. The August issue of The Spine Journal dedicated substantial space to studies attempting to shed light on the necessity of opioids, and how to anticipate and identify those most likely to succumb to addiction and opioid abuse. In addition to multiple studies on opioids, the issue’s editorial announced the publication of a supplement in the Journal of Bone and Joint Surgery containing research presented at a November 2019 Symposium on Pain Management Research.

The case series, “Opioid-free spine surgery: a prospective study of 244 consecutive cases by a single surgeon,” published by a group at Vanderbilt University Medical Center, tested whether opioids could be avoided completely for elective spine surgery.”

Richard A. Berkman, M.D. performed 244 spine surgeries that were stratified into less invasive or more invasive procedures for analysis. The first cohort of 66 patients were given the option of receiving opioids as needed, but were not scheduled to receive opioids. The second cohort of 178 patients were only given opioids in extreme cases of ‘breakthrough pain.’” Pain was measured at discharge, and one week and one month after surgery.

There was no significant difference in pain scores between the first and second cohorts at any time point after surgery. The rate of opioid use after surgery was significantly associated with both preoperative opioid use (those not taking opioids before surgery were less likely to take them after surgery), and whether they were in the first or second cohorts (those in the first were significantly more likely to use opioids after surgery).

The invasiveness of the procedure was not significantly associated with opioid use after surgery. The study provides evidence that efforts to wean patients off of opioids before surgery, and to not voluntarily provide opioids can lead to lower rates of opioid use without increased levels of postoperative pain.

Another study in the issue, “How does preoperative opioid use impact postoperative health-related quality of life scores for patients undergoing lumbar microdiscectomy?” investigated preoperative opioid use and did not find a difference in outcomes after lumbar microdiscectomy whether the patient used opioids before surgery or not. This study, however, did not report post-operative opioid use rates.

Also published in the issue, the study titled “Are preoperative depression and anxiety associated with patient-reported outcomes, health care payments, and opioid use after anterior discectomy and fusion?” found that anxiety and depression are associated with many negative outcomes after anterior cervical discectomy and fusion (ACDF) procedures.

The researchers at Johns Hopkins University found that preoperative diagnoses of depression or anxiety were associated with increased rates of multiday hospitalization, 90-day readmission, revision within 2 years, and postoperative opioid use. Additionally, depression resulted in a 2-year health care payment cost increase of $5,915. Anxiety resulted in an increase of $4,471 for the same measure. Interestingly, similar metrics on a shorter-term basis were not significantly increased.

Finally, a group at Stanford University developed a screening tool to predict postoperative opioid use. The publication, “A predictive-modeling based screening tool for prolonged opioid use after surgical management of low back and lower extremity pain,” describes the development of a model using data from MarketScan databases, a source covering about 50% of the American employer-insured population, and 40% of American retirees.

The study authors used 80% of the data to develop 7 models, and tested the models on the remaining 20% of the data. They found that the regression-based models offered the highest area under the curve (AUC) (0.835-0.847), a measure of the model’s accuracy, and relatively high sensitivity (74.9%-76.5%). The model identified high preoperative opioid use, number of days with an active opioid prescription and number of dosage increases between postoperative days 15-30 as the three strongest predictors of increased long-term opioid use.

The models also identified the number of dosage decreases in the 30-day postoperative period as the strongest negative indicator of long-term opioid use. The model is available online.

One strategy to reduce opioid use is through the use of non-opioid pain medications. Options range from over-the-counter drugs such as acetaminophen and ibuprofen to other prescription medications like gabapentinoids. Other drugs and drug combinations are currently in development, such as ZYNRELEF, which is a combination drug from Heron Therapeutics, Inc.

ZYNRELEF contains bupivacaine, a local anesthetic, with a low dose of the NSAID, meloxicam. The company recently announced positive news for the drug from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). Its two phase 3 studies found that ZYNRELEF significantly reduced pain and opioid use through 72 hours compared to bupivacaine alone.

Use of the drug after surgery also significantly increased the proportion of patients who required no postoperative opioids. It was tolerated as well as placebo or bupivacaine. The positive opinion from CHMP, recommending the drug for treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults, will be reviewed by the European Commission.

“Obtaining a positive opinion from the CHMP for ZYNRELEF is a major regulatory milestone and confirms the superiority of ZYNRELEF over bupivacaine solution, the current standard of care,” said Barry Quart, Pharm.D., president and chief executive officer of Heron. “We believe that the CHMP’s positive opinion of ZYNRELEF is an important step forward to help improve the lives of patients across the EU by significantly reducing the proportion of patients who experience severe pain after surgery.”

The company is currently awaiting decisions from the U.S. FDA and Health Canada after responding to questions from the regulatory bodies earlier this summer.

The conclusions of these studies aren’t necessarily surprising. In general, those who use opioids more before surgery will continue to do so after as well. But what is somewhat counterintuitive is that this is one of the few factors that actually predict long-term opioid use, more so than postoperative pain scores or invasiveness of the procedure.

In short, giving patients opioids leads patients to want or need more opioids. While more evidence will be helpful, it is fairly clear that there is much referring physicians and surgeons can already do to reduce opioid prescriptions through patient education, use of alternative pain-relief medication, and stopping the practice of sending everyone home with a prescription for an opioid drug.