Day-of-Surgery Gabapentinoids and Prolonged Opioid Use

A Retrospective Cohort Study of Medicare Patients Using Electronic Health Records

Jessica C. Young, PhD; Nabarun Dasgupta, PhD; Brooke A. Chidgey, MD; Til Stürmer, MD, PhD; Virginia Pate, MS; Michael Hudgens, PhD; Michele Jonsson Funk, PhD

Disclosures

Anesth Analg. 2021;133(5):1119-1128. 

In This Article

Discussion

Our analysis of preoperative gabapentinoid exposure in a cohort of Medicare patients undergoing major therapeutic surgical procedures at a large integrated health care delivery system found that 21.0% of patients were administered preoperative gabapentinoids. The observed risk of prolonged opioid use during the 90 days after surgery was relatively low, at 0.91%. The surgeries with the highest proportion of patients receiving preoperative gabapentinoids were colorectal resection, hip arthroplasty, knee arthroplasty, and hysterectomy.

Use of preoperative gabapentinoids increased throughout the study period, while the observed risk of prolonged opioid use decreased, suggesting that prescribing behaviors for perioperative pain management changed throughout the study period. The decreasing trend of prolonged opioid use was more dramatic in the gabapentinoid-exposed group compared to those who did not receive preoperative gabapentinoids. However, following IPTW adjustment, we did not find that gabapentinoids were associated with a reduced the risk of prolonged opioid use. Given the wide CI (adjRR, 1.19 [95% CI, 0.67–2.12]), neither a protective nor a harmful effect can be ruled out.

While many past studies have found a reduction in opioid consumption in the first 24–48 hours following surgery among patients who receive preoperative gabapentinoids, a recent systematic review found no clinically significant analgesic effect for perioperative gabapentinoid use.[4] Our study also did not find that preoperative gabapentinoids were associated with a reduction in the risk of postsurgical prolonged opioid use. A randomized controlled trial (RCT) conducted among patients undergoing a similar mix of surgeries found that perioperative gabapentin promoted opioid cessation (HR, 1.24 [95% CI, 1.00–1.54]). While we focused on gabapentinoids administered on the day of surgery, the RCT continued gabapentin administration for 72 hours following surgery. The mean age of patients in the RCT was also 16 years younger than patients in the current study (56.7 vs 72.7), and opioid cessation was based on self-report instead of prescription data. Further research into the potential impact of postsurgical gabapentinoids on the safety and efficacy of gabapentinoid use on opioid consumption following surgery is warranted.

Making causal inference in nonrandomized settings requires the assumption of no uncontrolled founding, an assumption that is impossible to verify and difficult to obtain in practice. While we controlled for potential confounding variables using propensity score methods, there likely remains unmeasured confounding that was not accounted for in these analyses. We were unable to measure the dosage of opioids administered perioperatively due to limitations in data availability for intravenously administered medications during surgery. Preoperative opioid use could be a proxy for preoperative pain and may also play a role in the amount of opioids prescribed postoperatively. We were unable to assess and account for potential differences in preoperative opioid administration. Unmeasured confounding may also be present due to changes in practice and increased caution with opioid prescribing during this study period. We controlled for time trends using 6-month increments as well as additional dates when ERAS protocols were put into place; however, it is possible that there remains residual confounding by elements associated with calendar time. While we conducted a stratified analysis splitting the surgeries into 2 time periods, a larger sample size allowing for more granular stratifications of calendar time and other factors for which the association may differ, such as surgical procedure, would be informative in future work.

This study used EHR data from a large integrated health care system. These data provide clinical details including inpatient medication orders; preoperative pain scores; patient status on admission; and patient details including BMI, smoking, and alcohol history, which are often unavailable in large population-based epidemiologic studies. However, the current data include only information for care provided and medication orders from a single health care system (which could contribute to underestimation of opioid use) and do not include pharmacy fulfillment information (which could contribute to overestimation of opioid use). To address this, we linked a subset of the cohort to Medicare claims data, conducted probabilistic bias analyses addressing potential misclassification of prolonged opioid use in the EHR data, and found that estimates remained above the null.

We also required that patients had 90 days of follow-up after surgery. Overall, 0.3% of patients died within 90 days after surgery, and examination of medical records found no evidence that any of the deaths were opioid related. This study was limited to patients age ≥65 years undergoing surgery in a single health system in the southeastern United States. Results may not be generalizable to younger populations or other systems and regions with differing surgical and prescribing practices. However, older patients represent an understudied and vulnerable population of interest, and these findings add to the limited evidence of the association of preoperative gabapentinoids on postsurgical opioid use.

Currently, the use of presurgical gabapentinoids has been recommended by diverse professional societies. However, gabapentinoid use for surgical pain is considered off-label use, and in 2019, the FDA issued a warning and labeling updates to address risks of breathing difficulties in patients who use gabapentinoids, particularly in combination with opioids.[5] Overall, we did not find that presurgical gabapentinoids were associated with a reduction in risk of prolonged opioid use. Given the limited clinical evidence supporting off-label effectiveness, caution is needed when prescribing these medications.[25,26] Attempts to reduce opioid abuse by shifting prescribing toward different drugs for pain management have the potential of unintentionally creating new avenues of abuse.[27,28] The off-label use of these medications to manage surgical pain should be carefully balanced against known harm, and more research is needed to understand the efficacy and safety of preoperative gabapentinoid use.

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