Liposome Bupivacaine for Postsurgical Analgesia in Adult Patients Undergoing Laparoscopic Colectomy: Results from Prospective Phase IV Sequential Cohort Studies Assessing Health Economic Outcomes.

Current Therapeutic Research 76 (2014) 1–6 Contents lists available at ScienceDirect Current Therapeutic Research journal homepage: www.elsevier.com/locate/cuthre Liposome Bupivacaine for Postsurgical Analgesia in Adult Patients Undergoing Laparoscopic Colectomy: Results from Prospective Phase IV Sequential Cohort Studies Assessing Health Economic Outcomes☆ Keith A. Candiotti, MD1,n, Laurence R. Sands, MD2, Edward Lee, MD3, Sergio D. Bergese, MD4, Alan E. Harzman, MD5, Jorge Marcet, MD6, Anjali S. Kumar, MD7, Eric Haas, MD8 1 Department of Anesthesiology, University of Miami Leonard Miller School of Medicine, Miami, Florida Department of Surgery, University of Miami School of Medicine, Miami, Florida 3 Department of Surgery, Albany Medical College, Albany, New York 4 Department of Anesthesiology and Neurological Surgery, Wexner Medical Center, The Ohio State University, Columbus, Ohio 5 Department of Surgery, Division of Colon and Rectal Surgery, Wexner Medical Center, The Ohio State University, Columbus, Ohio 6 Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, Florida 7 Department of Surgery, Section of Colon and Rectal Surgery, MedStar Washington Hospital Center, Washington, DC 8 Colorectal Surgical Associates, Ltd, LLP, Houston, Texas 2 a r t i c l e in fo a b s t r a c t Article history: Accepted 2 December 2013 Background: Opioid-based postsurgical analgesia exposes patients undergoing laparoscopic colectomy to elevated risk for gastrointestinal motility problems and other opioid-related adverse events (ORAEs). The purpose of our research was to investigate postsurgical outcomes, including opioid consumption, hospital length of stay, and ORAE risk associated with a multimodal analgesia regimen, employing a single administration of liposome bupivacaine as well as other analgesics that act by different mechanisms. Methods: We analyzed combined results from 6 Phase IV, prospective, single-center studies in which patients undergoing laparoscopic colectomy received opioid-based intravenous patient-controlled analgesia (PCA) or multimodal analgesia incorporating intraoperative administration of liposome bupivacaine. As-needed rescue therapy was available to all patients. Primary outcome measures were postsurgical opioid consumption, hospital length of stay, and hospitalization costs. Secondary measures included time to first rescue opioid use, patient satisfaction with analgesia (assessed using a 5-point Likert scale), and ORAEs. Results: Eighty-two patients underwent laparoscopic colectomy and did not meet intraoperative exclusion criteria (PCA n ¼ 56; multimodal analgesia n ¼ 26). Compared with the PCA group, the multimodal analgesia group had significantly lower mean total postsurgical opioid consumption (96 vs 32 mg, respectively; P o 0.0001) and shorter median postsurgical hospital length of stay (3.0 vs 4.0 days; P ¼ 0.0019). Geometric mean costs were $11,234 and $13,018 in the multimodal analgesia and PCA groups, respectively (P ¼ 0.2612). Median time to first rescue opioid use was longer in the multimodal analgesia group versus PCA group (1.1 hours vs 0.6 hours, respectively; P¼ 0.0003). ORAEs were experienced by 41% of patients receiving intravenous opioid PCA and 8% of patients receiving multimodal analgesia (P ¼ 0.0019). Study limitations included use of an open-label, nonrandomized design; small population size; and the inability to isolate treatment-related effects specifically attributable to liposome bupivacaine. Conclusions: Compared with intravenous opioid PCA, a liposome bupivacaine-based multimodal analgesia regimen reduced postsurgical opioid use, hospital length of stay, and ORAEs, and may lead to improved postsurgical outcomes following laparoscopic colectomy. & 2013. The Authors. Published by Elsevier Inc. All rights reserved. Key Words: hospitalization cost laparoscopic colectomy length of stay multimodal analgesia opioid-related adverse events surgery ☆ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. n Address correspondence to: Keith A. Candiotti, MD, Department of Anesthesiology, University of Miami Leonard M. Miller School of Medicine, 1611 NW 12th Ave, Central 300, Miami Beach, FL 33136. E-mail address: (K.A. Candiotti). Introduction As a result of their demonstrated efficacy, opioid analgesics continue to be the foundation for most postsurgical pain management regimens; however, opioid-related adverse events (ORAEs) exact a high toll in morbidity, hospital length of stay (LOS), and 0011-393X/$ - see front matter & 2013. The Authors. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.curtheres.2013.12.001 2 K.A. Candiotti et al. / Current Therapeutic Research 76 (2014) 1–6 hospitalization costs.1 Patients undergoing gastrointestinal (GI) surgery appear to be especially vulnerable to exacerbation of GI motility problems (postoperative ileus and small bowel obstruction).2,3 The management of postsurgical pain has been the focus of increasing attention during the past 3 decades; consensus recommendations for more effective postsurgical analgesia have been developed and published by government, regulatory, and medical organizations.4–7 Despite these efforts, improvement in reducing the incidence and severity of postsurgical pain has been slow. Patient surveys conducted during the past 2 decades have failed to demonstrate improvement over time, consistently reporting high incidences of postoperative pain ( 4 75% of surgical patients), with most affected patients describing their pain as moderate, severe, or extreme.8–10 The application of laparoscopic techniques in colectomy procedures has helped reduce postsurgical morbidity, pain severity, and LOS, although postsurgical pain remains a significant driver of prolonged recovery time.11 In the context of laparoscopic colectomy, multimodal analgesia has been shown to reduce postsurgical opioid use, pain, time to resumption of a normal diet, and LOS, in comparison with conventional intravenous (IV) opioidbased patient-controlled analgesia (PCA).12–14 Moreover, guidelines issued by the American Society of Anesthesiologists strongly endorse the use of multimodal analgesia in the perioperative setting whenever possible.4 Multimodal analgesic techniques involve the use of 2 or more analgesic drugs that act by different mechanisms delivered by the same or different routes of administration to improve pain control and minimize ORAEs.4,15 Liposome bupivacaine is a long-acting liposomal formulation of bupivacaine indicated for injection into the surgical site to produce postsurgical analgesia. In clinical studies involving a range of different surgical settings, liposome bupivacaine has been well tolerated and show (...truncated)