Does the available data support the use of liposomal bupivacaine for analgesia during vasectomy and vasectomy reversal procedures?

Introduction
Vasectomy is a safe and effective form of contraception that is undertaken by approximately half a million men in the United States each year.1 The procedure is commonly performed by urologists in the outpatient setting and involves isolating and occluding the vas deferens.2 Vasectomies are reversible, and reversals are requested by approximately 6% of patients.3

Effective perioperative pain management is crucial for patients undergoing vasectomy.2,4 The American Urological Association vasectomy guideline recommends local analgesia with or without oral sedation.4 However, intravenous sedation or general anesthesia can also be considered, especially for patients who cannot tolerate the procedure otherwise or if the vas is particularly difficult to isolate.2 Recommendations for pain management during vasectomy are based on expert opinion, as evidence surrounding optimal analgesic strategies in this setting is limited.4

Liposomal bupivacaine
Local analgesics commonly recommended in the literature for use during vasectomy include bupivacaine and lidocaine.2,4 Lidocaine has a quicker onset of action (~1 minute) but its effects only last for 0.5 to 2 hours without the addition of epinephrine.5 Conversely, bupivacaine has a slightly longer onset (~2 to 10 minutes) but its effects last for 2 to 4 hours. Bupivacaine has high lipid solubility and is highly bound to protein, characteristics which improve analgesic potency and duration of action, respectively. Bupivacaine is also available in several formulations, including a conventional solution for injection as well as a liposomal suspension for injection (Exparel®).6,7 All bupivacaine products can be used for perioperative local analgesia, but pivotal trials for these products did not specifically include patients undergoing vasectomy or vasectomy reversal.7 In comparison to conventional bupivacaine, liposomal bupivacaine carries the advantage of liposome technology that slowly disintegrates in-vivo, resulting in a sustained release of bupivacaine and prolonged analgesic effects (half-life, 9 to 34 hours).6 The pharmacological advantages of liposomal bupivacaine make this product a popular choice among surgeons. However, the liposomal formulation is associated with a significant cost increase compared to the conventional formulation.8

Studies describing the use of liposomal bupivacaine for perioperative analgesia in patients undergoing vasectomy or vasectomy reversal are summarized below.

Literature review
A retrospective chart review evaluated postoperative pain following penoscrotal surgery in 32 consecutive patients who received liposomal bupivacaine (266 mg/20 mL suspension diluted with 10 to 20 mL of injectable saline) via local infiltration at the operative site.9 Surgical procedures included placement of inflatable penile protheses (n= 22), vasectomy and/or hydrocelectomy (n=8), and circumcision/phalloplasty (n=2). Postoperative pain scores and opioid consumption were compared to a similar cohort of patients that did not receive liposomal bupivacaine. Authors reported that liposomal bupivacaine significantly reduced immediate and delayed postoperative pain intensity scores, delayed the time to first postoperative opioid use, and reduced total postoperative opioid consumption. No adverse events were reported. This study was published as an abstract, therefore, limited information was provided with regards to the study methodology, and no numerical results were provided. Importantly, patients were not stratified by procedure type, therefore, efficacy outcomes for patients undergoing vasectomy are uncertain.

A second retrospective study described andrological office-based procedures (using local analgesia only) and operating room procedures (using general or monitored anesthesia care) from 2014 to 2016.10 Liposomal bupivacaine diluted with normal saline to a final volume of 80 mL was administered via local infiltration at the beginning of the following procedures: vasectomy reversal (n=32), hydrocelectomy (n=24), testicular and microepididynal sperm aspiration (n= 24), circumcision (n=10), testicular and microepididymal sperm aspiration (n=9) spermatocelectomy (n= 4), orchiectomy (n=3), micro testicular microepididymal (n=2), testicular prosthesis (n=2), malleable penile prothesis (n=1), penile plication (n= 1), varicocelectomy (n= 1). For vasectomy reversal, 5 mL was used on the incision, 5 to 10 mL on each vas, and 5 to 10 mL on each testicular cord. Other forms of perioperative systemic analgesia were also allowed, and for patients undergoing vasectomy reversal, analgesia included acetaminophen, midazolam, and oxycodone. This study lacks specific outcome data regarding the effects of liposomal bupivacaine on perioperative outcomes. Nonetheless, the author group recommended liposomal bupivacaine for vasectomy reversal based on their experience, stating that alternative local analgesics such as lidocaine or non-liposomal bupivacaine do not provide a sufficient duration or depth of analgesia, respectively. Authors also cautioned against diluting liposomal bupivacaine beyond 60 to 80 mL due to loss of efficacy in the scrotum and penis.

Conclusion
Analgesia is an important concern for patients undergoing vasectomy and vasectomy reversal, but recommendations regarding preferred analgesics are limited.2,4 There is interest in using liposomal bupivacaine for vasectomy procedures due to this agent’s longer duration of action compared to other local anesthetics. However, the relatively higher cost of this agent compared to conventional local anesthetics may be restrictive.8 Two published retrospective studies have reported the use of liposomal bupivacaine in patients undergoing vasectomy.9,10 The first study found improved postoperative pain scores and reduced opioid consumption in a mixed population of patients undergoing penoscrotoal surgery who received liposomal bupivacaine compared to other local analgesics.9 The second study described the use of liposomal bupivacaine in patients undergoing andrological procedures in the ambulatory and inpatient setting.10 The author group recommended liposomal bupivacaine for vasectomy reversal based on their experience with the agent. Additional studies that compare conventional local analgesics with liposomal bupivacaine in vasectomy and vasectomy reversal are needed to make more robust conclusions about the superiority of liposomal bupivacaine in this setting.

References

  1. Zhang X, Eisenberg ML. Vasectomy utilization in men aged 18-45 declined between 2002 and 2017: Results from the United States National Survey for Family Growth data. Andrology. 2022;10(1):137-142. doi:10.1111/andr.13093
  2. Rogers MD, Kolettis PN. Vasectomy. Urol Clin North Am. 2013;40(4):559-568. doi:10.1016/j.ucl.2013.07.009
  3. Hua V, Chen L, Lundy S, Vij S. Vasectomy reversal search trends and advertising in the United States. J Urol. 2022 May;CME1(PD20-12):e2558. doi:10.1097/JU.0000000000002558.12
  4. Sharlip ID, Belker AM, Honig S, et al. Vasectomy: AUA guideline. J Urol. 2012;188(6 Suppl):2482-2491. doi:10.1016/j.juro.2012.09.080
  5. Gibbs MA, Wu T. Local and Regional Anesthesia. In: Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH, eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th ed. McGraw Hill; 2020. Accessed January 06, 2023. https://accessmedicine-mhmedical-com.proxy.cc.uic.edu/content.aspx?bookid=2353&sectionid=218707802
  6. Package insert. Pacira; 2018.
  7. Micromedex Solutions [database online]. Truven Health Analytics; 2023. Accessed January 06, 2023. http://www.micromedexsolutions.com/
  8. McCann ME. Liposomal bupivacaine: effective, cost-effective, or (just) costly? Anesthesiology;2021;134(2):139-142 doi:10.1097/ALN.0000000000003658
  9. Tapscott L and Hakim L. Bupivavaine extended-release liposome injectable suspension for postoperative pain management in penoscrotal urologic surgery. J Urol. 2013;189(4s):e501.
  10. Alom M, Ziegelmann M, Savage J, Miest T, Köhler TS, Trost L. Office-based andrology and male infertility procedures-a cost-effective alternative. Transl Androl Urol. 2017;6(4):761-772. doi:10.21037/tau.2017.07.34

Prepared by:
Salimata Ndir, PharmD Candidate Class of 2023
University of Illinois at Chicago College of Pharmacy

Reviewed by:
Katherine Sarna, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

February 2023

The information presented is current as January 5, 2022. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.