Clinical Evidence Does Not Support the use of Liposomal Bupivacaine, Leaving Patients Without Adequate Post-Surgical Pain Control

The 72-Hour Window for Post-Surgical Pain

Postoperative pain continues to be inadequately managed in a surprising proportion of patients and is associated with numerous negative clinical, patient-reported, and health economic outcomes.1-2 Moreover, poorly controlled acute pain after surgery has been consistently shown to be a predictive factor for the development of chronic pain. More effective analgesic/anesthetic perioperative measures may help prevent the adverse consequences of poorly controlled pain, including its transition to persistent pain and the associated dependence upon opioids.

Pain control following surgery is a priority for both the patient and the physician. Post-surgical pain control helps speed the patient’s recovery and reduces chances of complications, such as pneumonia, blood clots and opioid addiction. Pain needs to be managed carefully, with the patient and healthcare provider working together to come up with the right plan. Post surgical pain often extends beyond the duration of analgesia from a single administration of a local anesthetic like bupivacaine hydrochloride, both for periarticular and single shot nerve block. Current multimodal techniques generally provide adequate pain control for the first 24 hours or so; however, significant rebound effect can occur when these methods wear off (often when the patient has been rapidly discharged from an ambulatory surgery center).

A long sought-after goal is the ability to extend the duration of analgesia to 72 hours and beyond to prevent the rebound effect. Various adjuvants have been proposed but currently none have been approved to extend analgesia beyond 24 hours.3-6

Liposomal bupivacaine was developed with the goal of achieving that sought after 72-hour duration of postsurgical analgesia.7-8 The manufacturers hoped to accomplish this by encasing standard bupivacaine within a liposomal carrier to achieve a sustained release over time. In theory, this should provide a sustained release of bupivacaine. The pharmacokinetic data demonstrates that slow release of bupivacaine from liposomal carriers can be detected for 48 hours and beyond. However, the analgesic duration cannot be inferred from the time of bupivacaine detectability within the blood. The literature surrounding the supposed benefits of liposomal encapsulation has not supported the hypothesis of extended duration of analgesia.

Multiple reports in the peer-reviewed literature show no clinical difference between liposomal bupivacaine and standard bupivacaine with regard to duration of analgesia- both only achieve approximately 24 hours of postsurgical analgesia.9-11

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References:

  1. Rawal, Narinder, Current issues in postoperative pain management. European Journal of Anaesthesiology: March 2016 – Volume 33 – Issue 3 – p 160-171
  2. Nalini Vadivelu, MD Sukanya Mitra, MD, and Deepak Narayan, MD: Recent Advances in Postoperative Pain Management. Yale J Biol Med ;2010 Mar; 83(1): 11-25.
  3. Hussain N, Grzywacz VP, Ferreri CA, Atrey A, Banfield L, Shaparin N, Vydyanathan A: Investigating the efficacy of dexmedetomidine as an adjuvant to local anesthesia in brachial plexus block: A systematic review and meta-analysis of 18 randomized controlled trials. Reg Anesth Pain Med 2017; 42:184–96
  4. Abdallah FW, Brull R: Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: Asystematic review and meta-analysis. Br J Anaesth 2013; 110:915–25
  5. Albrecht E, Vorobeichik L, Jacot-Guillarmod A, Fournier N, Abdallah FW: Dexamethasone is superior to dexmedetomidine as a perineural adjunct for supraclavicular brachial plexus block: Systematic review and indirect meta-analysis. Anesth Analg 2019; 128:543–54 84.
  6. Hussain N, Van den Langenbergh T, Sermer C, Fontes ML, Atrey A, Shaparin N, Sawyer TR, Vydyanathan A: Equivalent analgesic effectiveness between perineural and intravenous dexamethasone as adjuvants for peripheral nerve blockade: A systematic review and meta-analysis. Can J Anaesth 2018; 65:194–206
  7. Bramlett K, Onel E, Viscusi ER, Jones K: A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee 2012; 19:530–6 27.
  8. Abildgaard JT, Chung AS, Tokish JM, Hattrup SJ: Clinical efficacy of liposomal bupivacaine: A systematic review of prospective, randomized controlled trials in orthopaedic surgery. JBJS Rev 2019; 7:e8
  9. Ilfeld BM, Gabriel RA, Eisenach JC: Liposomal bupivacaine infiltration for knee arthroplasty: Significant analgesic benefits or just a bunch of fat? Anesthesiology 2018; 129:623–6
  10. Hamilton TW, Athanassoglou V, Mellon S, Strickland LH, Trivella M, Murray D, Pandit HG: Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev 2017; 2:CD011419
  11. Abildgaard JT, Chung AS, Tokish JM, Hattrup SJ: Clinical efficacy of liposomal bupivacaine: A systematic review of prospective, randomized controlled trials inorthopaedic surgery. JBJS Rev 2019; 7:e8
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