Gabapentin as an adjunct to multimodal pain management following scrotal surgery

Recent studies in perioperative pain management have sought to identify opioid-sparing interventions that mitigate risks associated with opioid misuse, abuse, and accidental ingestion (1-8). This is particularly relevant in male infertility procedures where perioperative opioid prescribing has been shown to be associated with new persistent opioid use (9). Several opioid-related harm reduction efforts have been implemented in urology, including improved stewardship with opioid prescribing, use of novel local anesthetics, administration of perioperative oral or parenteral non-opioid pain medication, and interventions aimed at improving disposal of leftover opioid medication (1,3,6,10-12). In a recent trial published in the Journal of Urology, Punjani et al. report the results of a placebo-controlled, double-blind randomized trial assessing gabapentin’s efficacy in reducing pain and opioid utilization following scrotal surgery (13).

In addition to a multimodal pain regimen involving celecoxib, acetaminophen, and a local peripheral nerve block with bupivacaine, the authors randomized patients undergoing predominantly male infertility procedures to receive gabapentin or placebo orally within 2 hours of surgery followed by scheduled gabapentin orally for 3 days or an identical placebo. The authors should be commended for successfully conducting a double-blind, placebo-controlled trial in the perioperative setting. The authors found that the addition of gabapentin improved short-term pain scores postoperatively but did not alter opioid utilization or patient satisfaction with pain control.

As acknowledged by the authors, strengths of this study relate to its inherent design and research question. The authors adopted a methodologically rigorous study design, addressed unexpected variations in data collection, and answered a question that is highly relevant for surgeons performing scrotal surgery. In addition to the strengths identified in the paper, there are additional valuable aspects of the study worth noting. The trial boasts extensive postoperative data collected multiple times each day through postoperative day (POD) 7. These data offer insight into the natural history of pain following scrotal surgery, thereby providing potential points of intervention for pain management in future studies. Another strength was the administration of gabapentin pre- and postoperatively. Gabapentin, similar to other medications that modulate nociceptive pain signaling, may have improved efficacy in decreasing hyperalgesia postoperatively if given prior to iatrogenic insult (2). In this study, gabapentin was well-tolerated and had few adverse side effects, reinforcing its potential role in pain management following scrotal surgery. Moreover, gabapentin is an inexpensive and widely accessible medication that, if effective, could be feasibly incorporated into nearly any surgical practice, even those in resource-limited settings. Amidst ongoing national shortages in medical supplies, the identification of easily accessible and efficacious therapies is essential.

The authors note several limitations to the study including the heterogeneity of procedure type, incomplete data, and lack of medication compliance data. However, there are additional limitations that should be discussed, as they may influence whether gabapentin should be considered an effective therapy for managing perioperative pain following scrotal surgery and whether these findings are generalizable to other centers.

First, variability in the timing of self-reported pain score data collection may have influenced the findings, especially given that comparisons were made in relation to POD0 pain scores. For example, patients who submitted POD0 pain data in the recovery room may have submitted data prior to gabapentin’s onset of action (~2–3 hours with immediate release formulations) given that most of the included procedures take less than 2 hours to perform (14).

Second, differences in POD0 pain scores may be attributed to differences in pain management in the post anesthesia care unit (PACU) where anesthesia (rather than surgical) teams oversee medication administration, or differences in the effectiveness of the peripheral nerve block between arms. Patients in both arms received a peripheral nerve block with bupivacaine, which has a faster onset of action, more robust effect on targeting neuropathic and incisional pain, and longer duration (6–10 hours) than gabapentin (14). Patients receiving a peripheral nerve block with bupivacaine during scrotal procedures (without celecoxib or gabapentin) typically had minimal-to-no pain on the day or surgery (10). This suggests that any differences in pain scores on POD0 between arms were unlikely to be due to gabapentin alone.

Third, although the authors report a statistically significant reduction in pain scores that meet the threshold for minimal clinically important differences, objective pain scores in both arms are low. It is unclear whether the observed 1-point difference in pain scores among patients who are already experiencing minimal pain with the existing multimodal pain regimen justifies the routine addition of gabapentin. Additionally, pain is highly subjective and difficult to standardize between individuals. As such, it would have been beneficial to compare mean differences in pain scores from POD0 to POD7, with each participant acting as their own comparator rather than comparing mean pain scores between study arms on each postoperative day.

Lastly, the mean number of oxycodone pills consumed is higher than what is considered necessary for pain management following these procedures and more than double what was reported by the authors in a previous trial assessing celecoxib following similar procedures (15). Assuming higher need for pain medication in the first few days after surgery, the mean consumption of 13 pills of 5 mg oxycodone in each arm translates to opioid use every 6 hours through POD3–4. The high utilization of opioid medication in both arms may therefore have attenuated any benefit of gabapentin. The study participants’ opioid use is surprising considering roughly 2% of adolescent patients require opioid medication after POD3 for scrotal procedures (10,16). Many centers have successfully implemented opioid-free or heavily opioid-restricted (<10 pills of 5 mg oxycodone) protocols following major abdominal operations, such as robotic-assisted radical prostatectomy, without compromising patient satisfaction or pain scores, suggesting that shifts towards opioid-free or opioid-restricted treatment protocols should be implemented (1,6,17). Furthermore, it does not appear that there was standardization in the number of oxycodone pills prescribed empirically to patients following their procedure. This is relevant because studies have demonstrated that patients prescribed higher quantities of opioid medication are more likely to utilize higher morphine equivalents of opioid medication (4). Thus, discrepancies in the size of the opioid prescription may have attenuated differences in opioid utilization postoperatively.

When taken together, this trial provides reassuring data that gabapentin is well-tolerated in the postoperative period following scrotal procedures. Despite the limitations discussed above, gabapentin use was associated with significantly improved short-term pain scores. Future research should prioritize assessing the efficacy of gabapentin within the context of opioid-sparing protocols for outpatient scrotal surgery.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Andrology and Urology. The article has undergone external peer review.

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2024-704/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2024-704/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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