Liposomal Bupivacaine as a Foundation for Multimodal Analgesia in the Postoperative Setting

Case

A 50-year-old male with a history of benign prostatic hyperplasia (BPH), chronic obstructive pulmonary disease (COPD), and type 2 diabetes mellitus is admitted for a laparoscopic colectomy. The patient’s surgeon requests a pharmacy consultation to develop a multimodal, opioid-sparing pain control regimen.

Answer

Opioids have been the foundation of a multimodal approach to pain control for many years. In a study by Kessler and colleagues, 98% of patients undergoing a surgical procedure received an opioid-based pain regimen.¹ In a separate study, Apfelbaum and associates found that more than 50% of patients experienced an opioid-related adverse event (ORAE) within 2 weeks of surgery.² It is estimated that ORAEs increase hospital costs by approximately $4700 per admission and extend length of stay by 3 days.³

Due to the potential for ORAEs to cause serious harm and even death, the Joint Commission (JC) issued a sentinel event alert in August 2012.⁴ In this alert, the JC identified comorbidities that increased hospitalized patients’ risk for oversedation and respiratory depression. Postsurgical status, especially following upper abdominal or thoracic surgery, appears on the list. While the case at hand does not qualify as upper abdominal or thoracic surgery, the patient’s surgery and COPD put him into a high-risk category for respiratory complications, and his BPH puts him at risk for urinary retention secondary to opioids.

To avoid opioid-related complications, many practitioners are moving toward nonopioid analgesia. Crews recommended a 3-step approach to pain management: (1) acetaminophen, non-steroidal anti-inflammatories, cyclooxygenase-2 inhibitors, and local anesthetics utilized for mild to moderate pain; (2) intermittent opioid injections used for moderate to severe pain; and (3) peripheral nerve blocks and additional opioids for breakthrough pain.⁵ Employing this approach manages pain at a variety of levels via multiple mechanisms, while also reducing opioid use and associated ORAES.

Most local anesthetics have a relatively short duration of action compared with the duration of pain control necessary. For example, bupivacaine has a duration of action between 2 and 9 hours after local administration, while many patients have postoperative pain for 48 to 72 hours.⁶ The use of elastomeric pumps for continuous local administration of anesthetics has been trialed. While these devices provide good local pain control, they are not without issues. One disadvantage is that multiple pumps may be necessary to cover larger incision sites, while another is infection risk associated with indwelling devices.

A more recent means of extending the duration of bupivacaine was encapsulation in liposomes. By encapsulating bupivacaine into liposomes, the duration of action was extended for up to 72 hours, bringing patients to the end of the most painful postoperative period. Multiple studies^7-9 have demonstrated significant reduction in opioid use following local administration of liposomal bupivacaine at procedure close. In addition, Candiotti and colleagues⁹ showed a 24-hour reduction in length of stay following laparoscopic colectomy. These authors also showed a 33% reduction in ORAEs favoring the liposomal bupivacaine group. Finally, although not statistically significant, total hospitalization costs were also reduced in the liposomal bupivacaine group by $1784.

While liposomal bupivacaine carries the same adverse event profile as bupivacaine, it is important to note some additional precautions with its use. Administration of other amide-type local anesthetics (eg, lidocaine) may disrupt the liposome and can cause an immediate release of bupivacaine. It is recommended that liposomal bupivacaine be administered at least 20 minutes after lidocaine administration. It should also be noted that liposomal bupivacaine has not been studied in patients younger than 18 years.¹⁰

Based on this patient’s medical history and the physician’s request for an opioid-sparing regimen, this patient should receive liposomal bupivacaine infiltration at procedure close, with a concomitant opioid bolus regimen as needed for breakthrough pain. On the basis of the literature reviewed, a liposomal bupivacaine—based regimen should provide adequate pain control and could reduce the incidence of ORAEs, shorten length of stay, and decrease hospitalization cost.

Brian Faley, PharmD, BCPS, received his doctor of pharmacy degree from the Philadelphia College of Pharmacy of the University of the Sciences in Philadelphia in May 2004. He went on to complete a residency specializing in emergency medicine and toxicology at the Ernest Mario School of Pharmacy of Rutgers University and Robert Wood Johnson University Medical Center in June 2005. Currently, Dr. Faley is the clinical pharmacist for the emergency trauma department at Hackensack University Medical Center in Hackensack, New Jersey. His practice and research interests include emergency medicine, toxicology, disaster management, and pain management.

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References

• Kessler ER, Shah M, Gruschkus SK, Raju A. Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes. Pharmacother. 2013;33(4):383-391.
• Apfelbaum, JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003;97(2):534-540.
• Odera GM, Gan TJ, Johnson BH, Robinson SB. Effect of opioid-related adverse events on outcomes in selected surgical patients. J Pain Palliat Care Pharmacother. 2013;27(1):62-70.
• The Joint Commission. Safe use of opioids in hospitals. Joint Commission Sentinel Event Alert. 2012;49:1-5. www.jointcommission.org/assets/1/18/SEA_49_opioids_8_2_12_final.pdf. Accessed February 24, 2014.
• Crews JC. Multimodal pain management strategies for office-based and ambulatory procedures. JAMA. 2002;288(5):629-632.
• Bupivacaine. Lexi-Drugs [online database]. Hudson, OH: Lexi-Comp, Inc. Accessed February 24, 2014.
• Gorfine SR, Onel E, Patou G, Krivokapic KV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo controlled trial. Dis Colon Rectum. 2011;54(12):1552-1559.
• Golf M, Daniels SE Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam bupivacaine (extended-release bupivacaine local anesthetic) in bunionectomy. Adv Ther. 2011;28(9):776-788.
• Candiotti KA, Sands LR, Lee E, et al. Liposomal bupivacaine for postsurgical analgesia in adult patients undergoing laparoscopic colectomy: results from prospective phase IV sequential cohort studies assessing health economic outcomes. Curr Ther Res. 2014;76:1-6.
• EXPAREL [prescribing information]. Parsippany, NJ: Pacira Pharmaceuticals, Inc; 2011. Accessed February 24, 2014.