Liposome bupivacaine (EXPAREL®) for extended pain relief in patients undergoing ileostomy reversal at a single institution with a fast-track discharge protocol: an IMPROVE Phase IV health economics trial

Journal of Pain Research Dovepress open access to scientific and medical research S hort R eport Journal of Pain Research downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Open Access Full Text Article Liposome bupivacaine (EXPAREL®) for extended pain relief in patients undergoing ileostomy reversal at a single institution with a fast-track discharge protocol: an IMPROVE Phase IV health economics trial This article was published in the following Dove Press journal: Journal of Pain Research 26 July 2013 Number of times this article has been viewed Jon D Vogel Department of Colorectal Surgery, Cleveland Clinic, Digestive Disease Institute, Department of Colorectal Surgery, Cleveland, OH, USA Correspondence: Jon D Vogel Department of Colorectal Surgery, Cleveland Clinic Main Campus, Mail Code A30, 9500 Euclid Avenue, Cleveland, OH, USA 44195 Tel +1 216 444 3540 Fax +1 216 445 8627 Email submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/JPR.S46950 Powered by TCPDF (www.tcpdf.org) Background: Postoperative opioid use following ileostomy reversal procedures contributes to postoperative ileus. We assessed the impact of a liposome bupivacaine-based, opioid-sparing multimodal analgesia regimen versus a standard opioid-based analgesia regimen on postsurgical opioid use. We also assessed health economic outcomes in patients undergoing ileostomy reversal at our institution, which employs an enhanced recovery discharge protocol. Methods: In this single-center, open-label study, patients undergoing ileostomy reversal received postsurgical pain therapy via multimodal analgesia that included a single intraoperative administration of liposome bupivacaine or opioid-based patient-controlled analgesia (PCA) with intravenous morphine or hydromorphone. Rescue analgesia (intravenous [IV] opioids and/or oral opioid + acetaminophen) was available to all patients. Primary efficacy measures included postsurgical opioid use, hospital length of stay (LOS), and hospitalization costs. Secondary measures included: time to first rescue opioid use; patient satisfaction with analgesia; additional medical intervention; and opioid-related adverse events. Results: Forty-three patients were enrolled and met eligibility criteria (IV opioid PCA group = 20; liposome bupivacaine-based multimodal analgesia group = 23). Postsurgical opioid use was significantly less in the multimodal analgesia group compared with the IV opioid PCA group (mean [standard deviation]: 38 mg [46 mg] versus 68 mg [47 mg]; P = 0.004). Postsurgical LOS betweengroup differences (median: 3.0 days versus 3.8 days) and geometric mean hospitalization costs (US $6,611 versus US$6,790) favored the multimodal analgesic group but did not achieve statistical significance. Median time to first opioid use was 1.1 hours versus 0.7 hours in the multimodal analgesia and IV opioid PCA groups, respectively; P = 0.035. Two patients in the multimodal analgesia group and one in the IV opioid PCA group experienced opioid-related adverse events. Conclusion: A liposome bupivacaine-based multimodal analgesic regimen reduced postoperative opioid consumption in patients undergoing ileostomy reversal under a fast-track discharge protocol. A reduction of 21% in LOS (0.8 days) was noted which, although not statistically significant, may be considered clinically meaningful given the already aggressive fast-track discharge program. Keywords: surgery, ileostomy, multimodal analgesia, opioid-related adverse events, hospitalization cost, length of stay Introduction The rates of major and minor postoperative complications following ileostomy reversal procedures are reported to range between 22% and 33%.1–6 The incidence of small Journal of Pain Research 2013:6 605–610 © 2013 Vogel, 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. 605 Dovepress Journal of Pain Research downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Vogel bowel obstruction or postoperative ileus following ileostomy reversal may be as high as 12%.5–8 Further, a meta-analysis of 48 ileostomy reversal studies found that 7.2% of patients experienced bowel obstruction, more than one-third of whom (2.5%) required surgical intervention.9 Postoperative opioid use has been clearly identified as a predictor of gastrointestinal (GI) motility problems following abdominal surgery.10–13 The overall length of hospital stay (LOS) for patients undergoing ileostomy reversal varies widely in published reports; typical durations range between 4 days and 10 days.4,14,15 In recent years, there has been a trend toward use of enhanced or “fast-track” discharge protocols to reduce LOS in patients undergoing this procedure, predicated primarily on reducing the time to achieve tolerance of oral liquid/food intake and improved GI function.3,14,16–18 Recently, liposome bupivacaine (EXPAREL®; Pacira Pharmaceuticals, Inc, Parsippany, NJ, USA), a long-acting liposomal formulation of bupivacaine, has been made available for postsurgical analgesia. Liposome bupivacaine is indicated for administration into surgical sites to produce postsurgical analgesia.19 Clinical studies across a range of surgical settings demonstrated that a single intraoperative administration of liposome bupivacaine was well tolerated and provided postsurgical analgesia for up to 72 hours.20–22 These studies also showed that liposome bupivacaine extended the time to first opioid use and reduced per-patient opioid use overall.20,21 In the first published study from an ongoing series of liposome bupivacaine evaluations (designated IMPROVE, for Extended PaIn Relief Trial Utilizing the Infiltration of a Long-Acting Multivesicular LiPosome FoRmulation Of BupiVacaine, EXPAREL®), liposome bupivacaine, as part of a multimodal analgesic regimen, was compared with opioid-based patient-controlled analgesia (PCA) in patients undergoing open colectomy. This open-label, single-center study demonstrated that liposome bupivacaine-based multimodal analgesia led to significant reductions in hospital LOS, total cost of hospitalization, and postsurgical opioid use when compared with opioid-based PCA.23 The current study, part of the IMPROVE series, was a comparison of liposome bupivacaine-based multimodal analgesia with opioid-based PCA, with respect to total opioid burden and health economic outcomes in adult patients undergoing ileostomy reversal at an institution that already had an aggressive patient discharge protocol. Methods This was a Phase IV, prospective, single-center, open-label, sequential study designed to evaluate the efficacy, safety, 606 Powered by TCPDF (www.tcpdf.org) submit your manuscript | www.dovepress.com Dovepress and health economic outcomes associated with a multimodal analgesia regimen inclu (...truncated)