An extended paIn relief trial utilizing the infiltration of a long-acting Multivesicular liPosome foRmulation Of bupiVacaine, EXPAREL (IMPROVE): a Phase IV health economic trial in adult patients undergoing ileostomy reversal

Journal of Pain Research Dovepress open access to scientific and medical research O ri g inal R esearch Journal of Pain Research downloaded from https://www.dovepress.com/ by 146.200.5.46 on 29-Jun-2020 For personal use only. Open Access Full Text Article An extended paIn relief trial utilizing the infiltration of a long-acting Multivesicular liPosome foRmulation Of bupiVacaine, EXPAREL (IMPROVE): a Phase IV health economic trial in adult patients undergoing ileostomy reversal This article was published in the following Dove Press journal: Journal of Pain Research 17 July 2013 Number of times this article has been viewed Jorge E Marcet 1 Valentine N Nfonsam 2 Sergio Larach 3 Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; 2 Department of Surgery, University of Arizona Cancer Center, Tucson, AZ, USA; 3The Center for Colon and Rectal Surgery, Florida Hospital Cancer Institute, Orlando, FL, USA 1 Correspondence: Jorge E Marcet Department of Surgery, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL, USA Tel +1 813 844 4545 Fax +1 813 844 1920 Email submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/JPR.S46467 Powered by TCPDF (www.tcpdf.org) Background: Opioid analgesics are effective for postsurgical pain but are associated with opioid-related adverse events, creating a significant clinical and economic burden. Gastrointestinal surgery patients are at high risk for opioid-related adverse events. We conducted a study to assess the impact of an opioid-sparing multimodal analgesia regimen with liposome bupivacaine, compared with the standard of care (intravenous [IV] opioid-based, patientcontrolled analgesia [PCA]) on postsurgical opioid use and health economic outcomes in patients undergoing ileostomy reversal. Methods: In this open-label, multicenter study, sequential cohorts of patients undergoing ileostomy reversal received IV opioid PCA (first cohort); or multimodal analgesia including a single intraoperative administration of liposome bupivacaine (second cohort). Rescue analgesia was available to all patients. Primary outcome measures were postsurgical opioid use, hospital length of stay, and hospitalization costs. Incidence of opioid-related adverse events was also assessed. Results: Twenty-seven patients were enrolled, underwent the planned surgery, and did not meet any intraoperative exclusion criteria; 16 received liposome bupivacaine-based multimodal analgesia and eleven received the standard IV opioid PCA regimen. The multimodal regimen was associated with significant reductions in opioid use compared with the IV opioid PCA regimen (mean, 20 mg versus 112 mg; median, 6 mg versus 48 mg, respectively; P , 0.01), postsurgical length of stay (median, 3.0 days versus 5.1 days, respectively; P , 0.001), and hospitalization costs (geometric mean, $6482 versus $9282, respectively; P = 0.01). Conclusion: A liposome bupivacaine-based multimodal analgesic regimen resulted in statistically significant and clinically meaningful reductions in opioid consumption, shorter length of stay, and lower inpatient costs than an IV opioid-based analgesic regimen. Keywords: surgery, ileostomy, multimodal analgesia, opioid-related adverse events, hospitalization cost, length of stay Introduction The efficacy of opioid analgesics has led to their widespread adoption as the main component of perioperative and postsurgical pain control regimens.1,2 However, opioidrelated adverse events (ORAEs) create a significant clinical and economic burden in the postsurgical setting, including increased per-patient cost and length of stay (LOS).1–3 One 10-year study of admissions at a single hospital found that ORAEs were associated Journal of Pain Research 2013:6 549–555 549 © 2013 Marcet et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress Journal of Pain Research downloaded from https://www.dovepress.com/ by 146.200.5.46 on 29-Jun-2020 For personal use only. Marcet et al with a 16% increase in hospitalization costs and a 0.5-day increase in LOS.1 The risk and impact of ORAEs, including postoperative ileus and intestinal obstruction, appear to be dose-related and particularly severe in patients undergoing gastrointestinal (GI) surgery.4–9 Among patients undergoing ileostomy reversal, the overall rate of postsurgical complications (including ORAEs) is high, with reported complication rates ranging from 17% to 37%.10–20 GI motility complications (including postoperative ileus and intestinal obstruction or small bowel obstruction) are among the most frequent complications of ileostomy reversal, with reported rates of 5%–12%.11–17,19,20 Perioperative opioid use is likely to exacerbate the burden of GI motility and other complications.4–6,8 In a retrospective study of 279 patients who underwent elective colorectal surgery, Barletta et al6 showed that intravenous (IV) hydromorphone doses of as little as 2 mg per day were associated with about a 10-fold increase in postoperative ileus (odds ratio [OR] 9.9; 95% confidence interval [CI] 1.2 to 82.2; P = 0.03) compared with lower doses, and a median 1-day increase in length of hospital stay (5 days versus 4 days; P , 0.001). Conversely, a reduction in perioperative opioid use may be expected to reduce the risk of postoperative ORAEs, including those related to GI motility. Liposome bupivacaine is a multivesicular liposomal formulation of the local anesthetic bupivacaine (EXPAREL®; Pacira Pharmaceuticals, Inc; Parsippany, NJ, USA), designed to extend the duration of analgesia with a single administration. It is currently indicated for administration into the surgical site to produce postsurgical analgesia.21 In clinical studies involving five different surgical settings, the intraoperative administration of a single dose (range, 66 to 532 mg) of liposome bupivacaine has been shown to be well tolerated and to provide analgesia for up to 72 hours after administration.22,23 In addition to providing extended analgesia, liposome bupivacaine also increased the time to first opioid use and reduced the use of opioids overall.22,24 A series of open-label Phase IV studies (designated the PaIn Relief Trial Utilizing the Infiltration of a Long-Acting Multivesicular LiPosome FoRmulation Of BupiVacaine, EXPAREL [IMPROVE]) was designed to evaluate the impact of an opioid-sparing multimodal analgesic regimen incorporating liposome bupivacaine compared with opioid-based patient-controlled analgesia (PCA) on clinically meaningful and economically impactful postsurgical outcomes in three models of GI surgery (open colectomy, laparoscopic colectomy, and ileostomy reversal). Cohen25 previously reported results from a single-center open colectomy study, in which 550 Powered by TCPDF (www.tcpdf.org) submit your ma (...truncated)