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

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          Abstract

          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 = 56; multimodal analgesia n = 26). Compared with the PCA group, the multimodal analgesia group had significantly lower mean total postsurgical opioid consumption (96 vs 32 mg, respectively; P < 0.0001) and shorter median postsurgical hospital length of stay (3.0 vs 4.0 days; P = 0.0019). Geometric mean costs were $11,234 and $13,018 in the multimodal analgesia and PCA groups, respectively ( P = 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; P=0.0003). ORAEs were experienced by 41% of patients receiving intravenous opioid PCA and 8% of patients receiving multimodal analgesia ( P = 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.

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          Most cited references18

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          A clinical pathway to accelerate recovery after colonic resection.

          To investigate the feasibility of a 48-hour postoperative stay program after colonic resection. Postoperative hospital stay after colonic resection is usually 6 to 12 days, with a complication rate of 10% to 20%. Limiting factors for early recovery include stress-induced organ dysfunction, paralytic ileus, pain, and fatigue. It has been hypothesized that an accelerated multimodal rehabilitation program with optimal pain relief, stress reduction with regional anesthesia, early enteral nutrition, and early mobilization may enhance recovery and reduce the complication rate. Sixty consecutive patients undergoing elective colonic resection were prospectively studied using a well-defined postoperative care program including continuous thoracic epidural analgesia and enforced early mobilization and enteral nutrition, and a planned 48-hour postoperative hospital stay. Postoperative follow-up was scheduled at 8 and 30 days. Median age was 74 years, with 20 patients in ASA group III-IV. Normal gastrointestinal function (defecation) occurred within 48 hours in 57 patients, and the median hospital stay was 2 days, with 32 patients staying 2 days after surgery. There were no cardiopulmonary complications. The readmission rate was 15%, including two patients with anastomotic dehiscence (one treated conservatively, one with colostomy); other readmissions required only short-term observation. A multimodal rehabilitation program may significantly reduce the postoperative hospital stay in high-risk patients undergoing colonic resection. Such a program may also reduce postoperative ileus and cardiopulmonary complications. These results may have important implications for the care of patients after colonic surgery and in the future assessment of open versus laparoscopic colonic resection.
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            Opioid-related adverse drug events in surgical hospitalizations: impact on costs and length of stay.

            Opioid analgesics remain a mainstay in the treatment of pain associated with surgical procedures. Such use is associated with adverse drug events (ADEs). To investigate the impact of opioid-related ADEs on total hospital costs and length of stay (LOS) in adult surgical patients. This was a retrospective matched cohort study using data from computerized medical records. ADE cases were prospectively detected using computerized surveillance and verified by pharmacists. Surgical patients treated at LDS Hospital in Salt Lake City from January 1, 1998, to December 31, 2003, were included. The primary outcomes were costs and hospital LOS associated with opioid-related ADEs and the relationship of opioid dose to ADE events. Patients experiencing opioid-related ADEs had significantly increased median total hospital costs (7.4% increase; 95% CI 3.83 to 10.96; p < 0.001) and increased median LOS (10.3% increase; 95% CI 6.5 to 14.2; p < 0.001) compared with matched non-ADE controls. The increased costs attributable to ADEs, by surgery type, were general surgery ($676.51; 95% CI 351.50 to 1001.50), orthopedics ($861.50; 95% CI 448.20 to 1274.80), and obstetrics/gynecology ($540.90; 95% CI 281.40 to 800.40). Similarly, increased LOS attributable to ADEs, by surgery type, were general surgery (0.64 days; 95% CI 0.40 to 0.88), orthopedics (0.52 days; 95% CI 0.33 to 0.71), and obstetrics/gynecology (0.53 days; 95% CI 0.33 to 0.72). Higher doses of opioids were associated with increased risk of experiencing ADEs (OR 1.3; 95% CI 1.07 to 1.60; p = 0.01). Opioid-related ADEs following surgery were associated with significantly increased LOS and hospitalization costs. These ADEs occurred more frequently in patients receiving higher doses of opioids.
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              Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting.

              Assess comparative efficacy of liposome bupivacaine administered at doses ≤266 mg and bupivacaine HCl administered at doses ≤200 mg for postsurgical analgesia.
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                Author and article information

                Contributors
                Journal
                Curr Ther Res Clin Exp
                Curr Ther Res Clin Exp
                Current Therapeutic Research, Clinical and Experimental
                Elsevier
                0011-393X
                1879-0313
                27 December 2013
                27 December 2013
                December 2014
                : 76
                : 1-6
                Affiliations
                [1 ]Department of Anesthesiology, University of Miami Leonard Miller School of Medicine, Miami, Florida
                [2 ]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
                Author notes
                [* ]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. KCandiot@ 123456med.miami.edu
                Article
                S0011-393X(13)00036-2
                10.1016/j.curtheres.2013.12.001
                3994919
                25031661
                b491c5bc-f7bd-4876-80bd-f6e37ca559be
                © 2013 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 2 December 2013
                Categories
                Article

                hospitalization cost,laparoscopic colectomy,length of stay,multimodal analgesia,opioid-related adverse events,surgery

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