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Wang J, Long W, Qi Z, Liao Y, Li J. Analgesics use and risk of pancreatitis: result from the UK Biobank. Clin Res Hepatol Gastroenterol 2025:102616. [PMID: 40403927 DOI: 10.1016/j.clinre.2025.102616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 05/13/2025] [Accepted: 05/19/2025] [Indexed: 05/24/2025]
Abstract
BACKGROUND Pancreatitis, an inflammatory pancreatic disorder, arises from various etiologies including alcohol, tobacco, and drug use. Although the initiation of pancreatitis has been strongly linked to several medications, the association between analgesic use and pancreatitis risk remains ambiguous in population-based studies. METHODS This prospective cohort study involved 324,982 participants from the UK Biobank. Multivariable-adjusted Cox proportional-hazards models were conducted to evaluate the longitudinal association between incident pancreatitis risk and analgesics use, encompassing opioids, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, antimigraine preparations, and the mix. Subgroup and sensitivity analyses were conducted to assess the potential effects of baseline factors. RESULTS Over a median follow-up of 13.70 years, 2,303 cases of pancreatitis were identified. In the fully adjusted model, analgesics utilization increased the risk of pancreatitis (HR 1.13, 95% CI 1.04-1.23), acute pancreatitis (AP) (HR 1.11, 95% CI 1.01-1.22), and chronic pancreatitis (CP) (HR 1.25, 95% CI 1.00-1.56) (All the above p <0.05). Furthermore, participants who used opioids presented the highest risk of pancreatitis (HR 1.85, 95% CI 1.49-2.31, p <0.001), and the mixed group (HR 1.35, 95% CI 1.21-1.51, p <0.001) followed. Compared to the no analgesics group, the risk of both AP and CP also increased in the opioids and the mixed group. Subgroup analysis indicated that the impact of analgesics utilization on the pancreatitis risk may vary with certain covariates, such as age, cholelithiasis, etc. (p-interaction <0.05). CONCLUSION In this large population-based prospective cohort, analgesics utilization, particularly opioids and mixed analgesics, was linked to an increased risk of pancreatitis.
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Affiliation(s)
- Jiayi Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Wanxin Long
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Zehong Qi
- Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha 410078, China
| | - Yangjie Liao
- Department of Gastroenterology, Changde Hospital, Xiangya School of Medicine, Central South University (The first people's hospital of Changde city), Changde 415000, China
| | - Jingbo Li
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, China..
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Zeng J, He H, Song Y, Wei W, Han Y, Su X, Lyu W, Zhao J, Han L, Wu Z, Wang Z, Wei K. Adjuvant non-opioid analgesics decrease in-hospital mortality in targeted patients with acute pancreatitis receiving opioids. Eur J Gastroenterol Hepatol 2025; 37:263-271. [PMID: 39919002 PMCID: PMC11781558 DOI: 10.1097/meg.0000000000002868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/22/2024] [Indexed: 02/09/2025]
Abstract
OBJECTIVES Opioid administration in acute pancreatitis (AP) exacerbates its severity, prompting concerns regarding the increased requirement for intensive care and its potential impact on patient survival. We aimed to elucidate the influence of analgesic patterns on mortality among patients with AP hospitalized in the ICU. METHODS We included 784 patients (198 receiving opioid monotherapy and 586 receiving opioid polytherapy) from the Medical Information Mart for Intensive Care database. The primary outcome was in-hospital mortality. Propensity score matching was used to account for baseline differences. We used Kaplan-Meier survival curves and multivariate regression models to indicate survival discrepancies and potential associations. RESULTS Polytherapy group exhibited prolonged hospital survival (79.8 vs. 57.3 days, P < 0.001); polytherapy was associated with decreasing in-hospital mortality adjusted for confounders (HR = 0.49, 95% CI: 0.26-0.92; P = 0.027). Stratification analysis indicated that patients receiving adjunctive acetaminophen had prolonged hospital survival (opioid vs. opioid + acetaminophen, P < 0.001; opioid vs. opioid + NSAIDs + acetaminophen, P = 0.026). Opioid polytherapy benefited patients with APACHE III scores >83 and those with mean oral morphine equivalent >60 mg/day (HR = 0.17, 95% CI: 0.1-0.3, P < 0.001 and HR = 0.32, 95% CI: 0.2-0.52, P < 0.001, respectively). CONCLUSION Our findings suggest that an opioid-based analgesic regimen offers a survival advantage for patients with AP, particularly those in critical condition or with concerns about opioid use. This approach provides a viable clinical strategy for pain management. Further randomized clinical trials are warranted to validate these results.
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Affiliation(s)
- Jiahui Zeng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Hairong He
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Yiqun Song
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Wanzhen Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Yimin Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Xinhao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Weiqi Lyu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Jinpeng Zhao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Liang Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Zheng Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Zheng Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Kongyuan Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
- Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, People’s Republic of China
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
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Lucocq J, Joseph N, Knoph CS, Abu-El-Haija M, Scheers I, Drewes AM, Pandanaboyana S. Analgesia in paediatric acute pancreatitis: A scoping systematic review. J Pediatr Gastroenterol Nutr 2025; 80:203-208. [PMID: 39563649 DOI: 10.1002/jpn3.12418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/28/2024] [Accepted: 09/08/2024] [Indexed: 11/21/2024]
Abstract
OBJECTIVE Acute pancreatitis (AP) is a common paediatric condition, yet there is little data to support optimal analgesic practice. The aim of this scoping review was to report analgesic practice, investigate trends in analgesic strategy and evaluate the impact of analgesic modality on outcomes. METHODS A systematic search of Medline, Embase, CENTRAL, Pubmed Central and Google Scholar was performed by two independent investigators. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. RESULTS Three retrospective cohort studies, all conducted in North America, reported on analgesic practice in paediatric AP. The studies included 658 patients (median age, 12 years; female sex, 57%; non-biliary aetiology, 85.9%). Overall, analgesia was administered in 67% of patients, including opioids in 59.5% (43.8%-71.4%). Rates of acetaminophen (17.9% and 77.7%) and non-steroidal anti-inflammatory drugs (7.7% and 40.2%) were reported in two studies. Two studies reported reducing rates of opioid administration or reduced duration of opioid administration since 2017 and 2014, respectively. One study did not find any correlation between opioid administration and sociodemographic factors, length of stay or admission to intensive care units. No studies reported on complications or quality of life. No studies investigated non-medical modalities. There were no long-term data on analgesic use post-discharge. CONCLUSIONS Opioids are the mainstay of pain treatment in paediatric AP in North America. However, factors that influence the analgesic type, the impact of analgesic modality on the post-pancreatitis outcome and long-term analgesic use constitute a knowledge gap. Future studies are needed to inform analgesic use in paediatric AP.
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Affiliation(s)
- James Lucocq
- Department of General Surgery, NHS Lothian, Edinburgh, UK
| | - Nejo Joseph
- Palmerston North Hospital, Health New Zealand, Midcentral, Palmerston North, New Zealand
| | - Cecilie Sigaard Knoph
- Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University, Aalborg, Denmark
| | - Maisam Abu-El-Haija
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, College of Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
| | - Isabelle Scheers
- Paediatric Gastroenterology and Hepatology, Centre for Rare Pancreatic Diseases, Cliniques universitaires Saint-Luc, Woluwe-Saint-Lambert, Belgium
| | - Asbjorn M Drewes
- Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University, Aalborg, Denmark
| | - Sanjay Pandanaboyana
- HPB and Transplant Unit, Freeman Hospital, Newcastle Hospitals and NHS Foundation Trust, Newcastle Upon Tyne, UK
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
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Fliss B, Krishnarajah K, Ebert L, Wunder C, Franckenberg S. The Correlation of Bile Duct Dilatation in Postmortem Computed Tomography of Lethal Intoxication Cases for Different Drug Types-A Retrospective Study. Med Sci (Basel) 2024; 12:65. [PMID: 39584915 PMCID: PMC11587109 DOI: 10.3390/medsci12040065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 10/27/2024] [Accepted: 11/06/2024] [Indexed: 11/26/2024] Open
Abstract
PURPOSE To assess (I) whether, in autopsy-proven lethal intoxications with opiates/opioids, a dilatation of the common bile duct (CBD) is still visible in postmortem computed tomography (PMCT) and (II) if a dilatation of the CBD might also be measurable for other substance groups (e.g., stimulants, hypnotics, antipsychotics, etc.). METHODS We retrospectively measured the CBD using PMCT in cases with lethal intoxication (n = 125) and as a control group in cases with a negative toxicological analysis (n = 88). Intoxicating substances were classified into the subgroups (opiates, opioids, stimulants, hypnotics, antipsychotics, gasses, and others). Significance between the study and control groups was tested with the Mann-Whitney U test, and correlations were examined by using crosstables. RESULTS There was a statistically significant difference between the CBD diameters in the intoxication group overall, when compared to the CBD diameter in the control group (p < 0.001). For both subgroups of "opiates" and "opioids", there was a strong statistically significant difference between the CBD diameter (being wider) in those groups compared to the control group (both p = 0.001). For the three subgroups "hypnotics", "stimulants", and "psychotropic drugs", there was no statistically significant difference between the CBD diameters in the intoxication subgroups when compared with the control group. The other subgroups were too small for statistical analysis. CONCLUSION A dilated common bile duct in postmortem computed tomography might be used as an indication for a lethal opioid or opiate intoxication only in regard to the specific case circumstances or together with other indicative findings in a postmortem investigation.
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Affiliation(s)
- Barbara Fliss
- Institute of Legal Medicine, Johannes-Gutenberg University Mainz, 55131 Mainz, Germany
| | | | - Lars Ebert
- Zurich Forensic Science Institute, 8010 Zurich, Switzerland;
| | - Cora Wunder
- Institute of Legal Medicine, Johannes-Gutenberg University Mainz, 55131 Mainz, Germany
| | - Sabine Franckenberg
- Institute of Forensic Medicine, University of Zurich, 8057 Zurich, Switzerland (S.F.)
- Diagnostic and Interventional Radiology, University Hospital of Zurich, University of Zurich, 8091 Zurich, Switzerland
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Jahangir S, Khatua B, Smichi N, Rajalingamgari P, Narayana Pillai A, Summers MJ, McFayden B, Kostenko S, Gades NM, Singh VP. Buprenorphine affects the initiation and severity of interleukin-induced acute pancreatitis in mice. Am J Physiol Gastrointest Liver Physiol 2024; 327:G16-G24. [PMID: 38651230 DOI: 10.1152/ajpgi.00083.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/19/2024] [Accepted: 04/19/2024] [Indexed: 04/25/2024]
Abstract
Acute pancreatitis (AP) is a common disease with no targeted therapy and has varied outcomes ranging from spontaneous resolution to being lethal. Although typically painful, AP can also be painless. Various agents, including opioids, are used for pain control in AP; the risks and benefits of which are often debated. As experimental AP in mice is used to study the efficacy of potential therapies, we studied the effect of a commonly used opioid, buprenorphine, on the initiation and progression of AP. For this, we administered extended-release buprenorphine subcutaneously before inducing the previously established severe AP model that uses interleukins 12 and 18 (IL12,18) in genetically obese (ob/ob) mice and compared this to mice with AP but without the drug. Mice were monitored over 3 days, and parameters of AP induction and progression were compared. Buprenorphine significantly reduced serum amylase, lipase, pancreatic necrosis, and AP-associated fat necrosis, which is ubiquitous in obese mice and humans. Buprenorphine delayed the AP-associated reduction of carotid artery pulse distention and the development of hypothermia, hastened renal injury, and muted the early increase in respiratory rate versus IL12,18 alone. The site of buprenorphine injection appeared erythematous, inflamed, and microscopically showed thinning, loss of epidermal layers that had increased apoptosis. In summary, subcutaneous extended-release buprenorphine interfered with the induction of AP by reducing serum amylase, lipase, pancreatic and fat necrosis, the worsening of AP by delaying hypotension, hypothermia, while hastening renal injury, respiratory depression, and causing cutaneous injury at the site of injection.NEW & NOTEWORTHY Extended-release buprenorphine interferes with the initiation and progression of acute pancreatitis at multiple levels.
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Affiliation(s)
- Sarah Jahangir
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
| | - Biswajit Khatua
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
| | - Nabil Smichi
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
| | | | | | - Megan J Summers
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
| | - Bryce McFayden
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
| | - Sergiy Kostenko
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
| | - Naomi M Gades
- Department of Comparative Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
| | - Vijay P Singh
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States
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Aprea F, Millan Y, Tomás A, Campello GS, Calvo RN, Granados MDM. Percutaneous Fluoroscopic-Guided Celiac Plexus Approach: Results in a Pig Cadaveric Model. Animals (Basel) 2024; 14:1478. [PMID: 38791695 PMCID: PMC11117265 DOI: 10.3390/ani14101478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/12/2024] [Accepted: 05/14/2024] [Indexed: 05/26/2024] Open
Abstract
Celiac plexus block (CPB) and neurolysis (CPN) are used for pain management in people suffering from abdominal tumours or chronic pancreatitis. The fluoroscopically guided approach common in human medicine has not been described in veterinary settings. The aim of this study was to describe a fluoroscopic approach to the celiac plexus (CP) in fresh pig cadavers. Twelve animals were included in the procedure. Cadavers were positioned in sternal position and, under fluoroscopic guidance, a Chiba needle was inserted parasagittal at 6 cm from the spinal midline at the level of the last thoracic vertebra. From the left side, the needle was directed medio-ventrally with a 45° angle towards the T15 vertebral body; once the vertebral body was contacted, the needle was advanced 1 cm ventrally towards the midline. Iodinated contrast was injected to confirm the location. Following this, 2 mL of dye (China ink) was injected. A laparotomy was performed, and dyed tissue was dissected and prepared for both histochemical and immunohistochemical techniques. In 10 out of 12 samples submitted for histological evaluation, nervous tissue belonging to CP was observed. Fluoroscopy guidance allows for feasible access to the CP in swine cadavers in this study. Further studies are warranted to determine the efficacy of this technique in swine and other veterinary species.
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Affiliation(s)
| | - Yolanda Millan
- Department of Comparative Pathology, School of Veterinary Medicine, University of Cordoba, 14071 Cordoba, Spain
| | - Anna Tomás
- Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), 07120 Palma, Spain; (A.T.); (G.S.C.)
| | - Gemma Sempere Campello
- Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), 07120 Palma, Spain; (A.T.); (G.S.C.)
| | - Rocio Navarrete Calvo
- Animal Medicine and Surgery Department, School of Veterinary Medicine, University of Cordoba, 14071 Cordoba, Spain; (R.N.C.); (M.d.M.G.)
| | - Maria del Mar Granados
- Animal Medicine and Surgery Department, School of Veterinary Medicine, University of Cordoba, 14071 Cordoba, Spain; (R.N.C.); (M.d.M.G.)
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Shirai H, Tsukada K. Understanding bacterial infiltration of the pancreas through a deformable pancreatic duct. J Biomech 2024; 162:111883. [PMID: 38064997 DOI: 10.1016/j.jbiomech.2023.111883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/20/2023] [Accepted: 11/22/2023] [Indexed: 01/16/2024]
Abstract
Tiny amount of bacteria are found in the pancreas in pancreatitis and cancer, which seemed involved in inflammation and carcinogenesis. However, bacterial infiltration from the duodenum is inhibited by the physical defense mechanisms such as bile flow and the sphincter of Oddi. To understand how the bacteria possibly infiltrate the pancreas through a deformable pancreatic duct, influenced by the periodic contractions of the sphincter of Oddi, a mathematical model of bacterial infiltration is developed that considered large deformation, fluid flow, and bacterial transport in a deformable pancreatic duct. In addition, the sphincter's contraction wave is modeled by including its propagation from the pancreas toward the duodenum. Simulated structure of the deformed duct with the relaxed sphincter and simulated bile distribution agreed reasonably well with the literature, validating the model. Bacterial infiltration from the duodenum in a deformable pancreatic duct, following the sphincter's contraction, is counteracted by a gradual peristalsis-like deformation of the pancreatic duct, due to an antegrade contraction wave propagation from the pancreas to the duodenum, Parametric sensitivity analysis demonstrated that bacterial infiltration is increased with lower bile and pancreatic juice flow rate, greater contraction amplitude and frequency, thinner wall thickness, and retrograde contraction wave propagation. Since contraction waves following retrograde propagation are increased in patients with common bile duct stones and pancreatitis, they may possibly be factors for continuum inflammation of pancreas. (224 words).
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Affiliation(s)
- Hiroaki Shirai
- Graduate School of Science and Technology, Keio University, 3-14-1 Hiyoshi Kohoku-ku, Yokohama-shi, Kanagawa 223-8522, Japan.
| | - Kosuke Tsukada
- Graduate School of Science and Technology, Keio University, 3-14-1 Hiyoshi Kohoku-ku, Yokohama-shi, Kanagawa 223-8522, Japan; Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi Kohoku-ku, Yokohama-shi, Kanagawa 223-8522, Japan
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Boyev A, Prakash LR, Chiang YJ, Childers CP, Jain AJ, Newhook TE, Bruno ML, Arvide EM, Dewhurst WL, Kim MP, Ikoma N, Lee JE, Snyder RA, Katz MHG, Tzeng CWD, Maxwell JE. Postoperative Opioid Use Is Associated with Increased Rates of Grade B/C Pancreatic Fistula After Distal Pancreatectomy. J Gastrointest Surg 2023; 27:2135-2144. [PMID: 37468733 DOI: 10.1007/s11605-023-05751-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/03/2023] [Indexed: 07/21/2023]
Abstract
BACKGROUND Clinically relevant postoperative pancreatic fistula (CR-POPF) is a major source of morbidity after distal pancreatectomy. This study examined the association between postoperative opioid use and CR-POPF in the context of opioid-sparing postoperative care. METHODS A case-control study was performed on consecutive patients who underwent distal pancreatectomy between October 2016 and April 2022 at a single institution. Patients who developed CR-POPF were compared to controls. Multivariable regression modeling was used to identify factors associated with CR-POPF. RESULTS A total of 281 patients underwent 187 open, 20 laparoscopic, and 74 robotic-assisted operations. The rate of CR-POPF was 21% (n = 58). CR-POPF rate declined from 32 to 8% over the study period (p < 0.001). Median oral morphine equivalents (OME) administered on POD 0-1 and 0-3 were 94 and 129 mg, respectively, in patients who did not develop a fistula versus 130 and 180 mg in those who did (both p ≤ 0.001). POD 0-3 OME (OR 1.11, p = 0.044) was independently associated with increased odds of CR-POPF, with each additional 50 mg (equivalent to 10 tramadol pills) increasing the relative risk by 11% and absolute risk by 2%. CONCLUSION Early postoperative opioid use after distal pancreatectomy was associated with increased odds of CR-POPF. Decreasing perioperative opioid use through enhanced postoperative management is a low-cost and generalizable approach that may reduce rates of CR-POPF after distal pancreatectomy.
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Affiliation(s)
- Artem Boyev
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Christopher P Childers
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Anish J Jain
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Morgan L Bruno
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Elsa M Arvide
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Whitney L Dewhurst
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Rebecca A Snyder
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Jessica E Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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Sotoudehmanesh R, Ali Asgari A, Bagheri M, Rahimi R. Opium Effects on Pancreatobiliary System in Opium Abusers Evaluated by Endoscopic Ultrasonography. Middle East J Dig Dis 2023; 15:231-234. [PMID: 38523890 PMCID: PMC10955991 DOI: 10.34172/mejdd.2023.351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 07/20/2023] [Indexed: 03/26/2024] Open
Abstract
Background: Opium use is a significant social and public health issue. There are numerous effects of opium documented as affecting the pancreatobiliary system. The aim of the study was to assess the pancreatobiliary changes in patients with opium addiction by endoscopic ultrasonography (EUS). Methods: During the study period, consecutive patients who were referred for EUS of submucosal upper gastrointestinal lesions were included. The history of opium addiction and clinical symptoms were recorded prospectively. Diameters of the common bile duct (CBD), pancreatic duct (PD), size of the ampulla of Vater, and gallbladder abnormalities were evaluated using EUS. Results: A total of 254 patients (53.1% male, mean age of 55.4±14.2 years) were studied. A history of opium addiction was present in 56 patients (22.0%). Choledocholithiasis was found in two patients (3.6%) and one control (0.5%) patient (P=0.06). Gallbladder stones were found in 13 opium-addict (23.2%) and 16 control (8.1%) patients (P=0.002). The mean diameter of the CBD, size of the ampulla of Vater (P<0.001), and PD (P=0.04) were all significantly greater in patients with opium addiction. Conclusion: Dilation of the biliary and PDs is seen more commonly in patients addicted to opium. However, the clinical implications of these findings need to be further evaluated in future studies.
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Affiliation(s)
- Rasoul Sotoudehmanesh
- Liver and Pancreaticobiliary Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Ali Asgari
- Liver and Pancreaticobiliary Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Bagheri
- Liver and Pancreaticobiliary Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Roya Rahimi
- Liver and Pancreaticobiliary Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Manrai M, Dawra S, Singh AK, Jha DK, Kochhar R. Controversies in the management of acute pancreatitis: An update. World J Clin Cases 2023; 11:2582-2603. [PMID: 37214572 PMCID: PMC10198120 DOI: 10.12998/wjcc.v11.i12.2582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/22/2023] [Accepted: 03/29/2023] [Indexed: 04/25/2023] Open
Abstract
This review summarized the current controversies in the management of acute pancreatitis (AP). The controversies in management range from issues involving fluid resuscitation, nutrition, the role of antibiotics and antifungals, which analgesic to use, role of anticoagulation and intervention for complications in AP. The interventions vary from percutaneous drainage, endoscopy or surgery. Active research and emerging data are helping to formulate better guidelines. The available evidence favors crystalloids, although the choice and type of fluid resuscitation is an area of dynamic research. The nutrition aspect does not have controversy as of now as early enteral feeding is preferred most often than not. The empirical use of antibiotics and antifungals are gray zones, and more data is needed for conclusive guidelines. The choice of analgesic is being studied, and the recommendations are still evolving. The position of using anticoagulation is still awaiting consensus. The role of intervention is well established, although the modality is constantly changing and favoring endoscopy or percutaneous drainage rather than surgery. It is evident that more multicenter randomized controlled trials are required for establishing the standard of care in these crucial management issues of AP to improve the morbidity and mortality worldwide.
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Affiliation(s)
- Manish Manrai
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | - Saurabh Dawra
- Department of Medicine and Gastroenterology, Command Hospital, Pune 411040, India
| | - Anupam K Singh
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Daya Krishna Jha
- Department of Gastroenterology, Army Hospital (Research and Referral), New Delhi 11010, India
| | - Rakesh Kochhar
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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Beheshti Namdar A, AkbariRad M, Farzaneh Far M, Ahadi M, Hosseini SM, Firoozi A, Shoraka O, Ataee Karizmeh M, Moodi Ghalibaf A. Addiction and the Risk of Common Bile Duct Stones: A 4-Year Retrospective Population-Based Study in Mashhad, Iran. ADDICTION & HEALTH 2023; 15:100-104. [PMID: 37560391 PMCID: PMC10408761 DOI: 10.34172/ahj.2023.1382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 09/12/2022] [Indexed: 08/11/2023]
Abstract
BACKGROUND As a common digestive disorder, choledocholithiasis can have serious consequences, including death. Given that opioids have been shown to contribute to the spasm of Oddi's sphincter, which results in biliary stasis in the common bile duct (CBD), it is likely that opioids can also raise the prevalence of choledocholithiasis. In this regard, this study aimed to investigate how common opium addiction was among choledocholithiasis patients in Mashhad, Iran. METHODS The current retrospective observational study was conducted on 599 patients with choledocholithiasis who underwent endoscopic retrograde cholangiopancreatography (ERCP), utilizing information gathered at the Ghaem hospital in Mashhad, Iran, between 2011 and 2015. Patient data were collected from files and records using certain criteria such as gender, opium addiction, hepatic enzymes (AST, ALT, ALP), plasma levels of total bilirubin, and direct bilirubin. The size of the CBD stones as well as the correlation between the gallbladder and CBD stones were calculated. FINDINGS From among 599 patients included, 345 (57.6%) were female and 254 (42.4%) were male. Moreover, 195 patients (32.2%) had opiate addictions. The size of the CBD stone was correlated with the patient's age (r=0.17, P=0.001). The average stone measured 12.22±3.32 mm. There were notable differences in the mean size of the CBD stone (P<0.001) between addicted and non-addicted cases; specifically, the mean CBD stone size in addicted cases was 12.715.13 mm while it was 12.34.33 mm in non-addicted cases. CONCLUSION This study showed patients with CBD stones have a higher rate of opium addiction compared to the general population, indicating a possible link between the two conditions.
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Affiliation(s)
- Ali Beheshti Namdar
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mina AkbariRad
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Farzaneh Far
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mitra Ahadi
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mousalreza Hosseini
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abdollah Firoozi
- Pharmacist, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Omid Shoraka
- Medical Doctor, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehdi Ataee Karizmeh
- Student Research Committee, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - AmirAli Moodi Ghalibaf
- Student Research Committee, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
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The Association Between Opioid Use and Opioid Type and the Clinical Course and Outcomes of Acute Pancreatitis. Pancreas 2022; 51:523-530. [PMID: 35835104 DOI: 10.1097/mpa.0000000000002052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Basic science studies suggest that opioids aggravate disease severity and outcomes in acute pancreatitis. We sought to determine the association of opioid use and opioid type with the clinical course and outcome of acute pancreatitis. METHODS In this retrospective single-center observational study, we included all adult patients admitted with acute pancreatitis between 2008 and 2021. Patients were classified into 3 groups based on analgesia type: morphine, noonmorphine opioid, and nonopioid. RESULTS We included 2308 patients. Of the patients, 343 (14.9%) were treated with morphine, 733 (31.8%) were treated with nonmorphine opioids, and 1232 (53.4%) patients were in the nonopioid group. The incidence of 30-day mortality did not differ significantly between study groups: 3.9%, 2.9%, and 4.4% in the nonopioid, nonmorphine-opioid, and morphine groups, respectively ( P = 0.366).In multivariate analysis, the composite end point consisting of 30-day mortality, invasive ventilation, emergent abdominal surgery, and need for vasopressors was significantly more likely to occur in the morphine group than in the nonopioid group (adjusted odds ratio, 1.69; 95% confidence interval, 1.1-2.598; P = 0.01). CONCLUSIONS Mortality among acute pancreatitis patients did not differ significantly between patients receiving morphine, nonmorphine opioids, and nonopioids. However, morphine treatment was associated with higher rates of some serious adverse events.
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Hayashi Y, Shimeno K, Tamura S, Naruko T. Severe sphincter of Oddi spasm after cryoballoon ablation: a case report of an unusual complication after atrial fibrillation ablation. Eur Heart J Case Rep 2022; 6:ytac082. [PMID: 35224440 PMCID: PMC8867818 DOI: 10.1093/ehjcr/ytac082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 11/11/2021] [Accepted: 02/02/2022] [Indexed: 12/05/2022]
Abstract
Background Perioesophageal vagal nerve (VN) injury after atrial fibrillation (AF) ablation remains an important complication. The VN provides parasympathetic innervation to the majority of the abdominal organs—including the stomach and the sphincter of Oddi (SO)—and regulates smooth muscle contraction. We present an unusual case of SO spasm induced by VN injury after cryoballoon ablation (CBA). Case summary A 71-year-old woman presented to our institution with paroxysmal AF. The patient had a history of cholecystectomy and SO dysfunction. She had undergone CBA for AF. Immediately after the procedure, the patient developed epigastric pain. Computed tomography showed dilation of the intra- and extrahepatic bile ducts, with the diameter of the common bile duct measuring ∼15.6 mm. Blood tests on postoperative Day 1 revealed severely elevated aminotransferase levels (aspartate aminotransferase, 3156 U/L; alanine aminotransferase, 2084 U/L; lactate dehydrogenase, 2279 U/L; total bilirubin 1.7 mg/dL). Discussion It is known that VN denervation induces SO spasms. The right and left vagal trunks descend alongside the oesophagus, forming a perioesophageal plexus and innervating most of the gastrointestinal organs. In our case, SO spasm was induced as a result of the perioesophageal plexus injury caused by CBA. Underlying SO dysfunction and post-cholecystectomy also played an important role. Coupled with the absence of the gallbladder, which is the reservoir of bile juice and coordinator of SO, SO spasm caused severe elevation of the bile duct pressure. Care should be taken when performing AF ablation with regards to the stomach and the SO.
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Affiliation(s)
- Yusuke Hayashi
- Department of Cardiology, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan
| | - Kenji Shimeno
- Department of Cardiology, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan
| | - Shota Tamura
- Department of Cardiology, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan
| | - Takahiko Naruko
- Department of Cardiology, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan
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Abstract
The pancreatic enzymes lipase and amylase serve important functions in digestion/absorption of fats and polysaccharides. Measurement of these enzymes is often used in the emergency department to rule out acute pancreatitis in patients with nonspecific abdominal pain. In acute pancreatitis, serial measurements of plasma lipase and amylase typically follow a predictable temporal pattern of rise-and-fall kinetics: lipase levels rise within 4 to 8 hours, crest at 2× to 50× the upper reference limit at 24 hours, and decline to normal concentrations in 7 to 14 days. In situations in which the duration and magnitude of pancreatic enzyme elevation are more transient, clinicians should consider alternative causes for enzyme elevation. In this case report, incidental discovery of elevated lipase in an African American baby girl who ingested oxycodone resulted in additional laboratory and radiological work-up. Stronger awareness of exogenous influences on gastrointestinal motility may have prevented the need for further testing in this patient.
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Affiliation(s)
- Iván González
- Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri
| | - Stephen Roper
- Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri
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IL-10-1082G>A polymorphism, use of opioids and age affect the course of acute pancreatitis. Eur J Gastroenterol Hepatol 2021; 32:178-185. [PMID: 32804849 DOI: 10.1097/meg.0000000000001875] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE We aimed to determine the association of two of the most important functional polymorphisms of IL-8 and IL-10 with the clinical course and outcome of acute pancreatitis. METHOD Ninety-three patients with acute pancreatitis were genotyped for IL-8-251T>A and IL-10-1082G>A using PCR-RFLP. The severity of the disease was determined based on the Atlanta Classification system. RESULTS In patients treated with opioids, the odds for severe form of acute pancreatitis, its complications, and death were increased. Advanced age was associated with higher odds of organ/multiple organ failure and other systemic complications. Multivariate logistic regression analyses confirmed the observed effect of age and use of opioids, and revealed higher odds for the development of severe form of acute pancreatitis [P = 0.017, odds ratio (OR): 4.324, 95% confidence interval (CI): 1.305-14.323], its complications in general (P = 0.011, OR: 4.936, 95% CI: 1.442-16.897), pancreatic necrosis (P = 0.032, OR: 3.922, 95% CI: 1.122-13.707) and systemic inflammatory response syndrome (P = 0.037, OR: 3.838, 95% CI: 1.085-13.583) in the absence of IL-10-1082G>A variant allele. The effect of IL-8 -251T>A on acute pancreatitis severity or mortality was not detected. CONCLUSION Our study suggests the IL-10 -1082A allele as a protective factor in acute pancreatitis. Opioid analgesics treatment in acute pancreatitis is associated with severity, complications and mortality, while advanced age increases the risk of systemic complications.
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Increased Risk of Acute Pancreatitis with Codeine Use in Patients with a History of Cholecystectomy. Dig Dis Sci 2020; 65:292-300. [PMID: 31468265 DOI: 10.1007/s10620-019-05803-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 08/12/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy. AIMS To assess the association between codeine use and acute pancreatitis in patients with a previous cholecystectomy. METHODS We conducted a retrospective nested case-control study using the 2005-2015 MarketScan® Commercial Claims and Encounters Database. The cohort included patients aged 18-64; cohort entry began 365 days after cholecystectomy. Odds ratios (ORs) and 95% CIs for acute pancreatitis hospitalization were estimated comparing use of codeine with non-use of codeine. In a secondary analysis, use of codeine was compared with an active comparator: use of non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS Of the 664,083 patients included in the cohort, 1707 patients were hospitalized for acute pancreatitis (incidence 1.1 per 1000 person-years) and were matched to 17,063 controls. Compared with non-use of codeine, use of codeine was associated with an increased risk of acute pancreatitis (OR 2.67; 95% CI 1.63, 4.36), particularly elevated in the first 15 days of codeine use (OR 5.37; 95% CI 2.70, 10.68). Compared with use of NSAIDs, use of codeine was also associated with an increased risk of acute pancreatitis (OR 2.64; 95% CI 1.54, 4.52). CONCLUSION Codeine is associated with an increased risk of acute pancreatitis in patients who have previously undergone cholecystectomy; greater clinician awareness of this association is needed.
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18
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Billington S, Shoner S, Lee S, Clark-Snustad K, Pennington M, Lewis D, Muzi M, Rene S, Lee J, Nguyen TB, Kumar V, Ishida K, Chen L, Chu X, Lai Y, Salphati L, Hop CECA, Xiao G, Liao M, Unadkat JD. Positron Emission Tomography Imaging of [ 11 C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporin A. Clin Pharmacol Ther 2019; 106:1056-1066. [PMID: 31102467 DOI: 10.1002/cpt.1506] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 04/25/2019] [Indexed: 01/16/2023]
Abstract
Using positron emission tomography imaging, we determined the hepatic concentrations and hepatobiliary transport of [11 C]rosuvastatin (RSV; i.v. injection) in the absence (n = 6) and presence (n = 4 of 6) of cyclosporin A (CsA; i.v. infusion) following a therapeutic dose of unlabeled RSV (5 mg, p.o.) in healthy human volunteers. The sinusoidal uptake, sinusoidal efflux, and biliary efflux clearance (CL; mL/minute) of [11 C]RSV, estimated through compartment modeling were 1,205.6 ± 384.8, 16.2 ± 11.2, and 5.1 ± 1.8, respectively (n = 6). CsA (blood concentration: 2.77 ± 0.24 μM), an organic-anion-transporting polypeptide, Na+ -taurocholate cotransporting polypeptide, and breast cancer resistance protein inhibitor increased [11 C]RSV systemic blood exposure (45%; P < 0.05), reduced its biliary efflux CL (52%; P < 0.05) and hepatic uptake (25%; P > 0.05) but did not affect its distribution into the kidneys. CsA increased plasma concentrations of coproporphyrin I and III and total bilirubin by 297 ± 69%, 384 ± 102%, and 81 ± 39%, respectively (P < 0.05). These data can be used in the future to verify predictions of hepatic concentrations and hepatobiliary transport of RSV.
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Affiliation(s)
- Sarah Billington
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.,Drug Metabolism and Pharmacokinetics, Vertex Pharmaceuticals (Europe) Ltd., Abingdon-on-Thames, UK
| | - Steven Shoner
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Scott Lee
- Inflammatory Bowel Disease Program, University of Washington, Seattle, Washington, USA
| | - Kindra Clark-Snustad
- Inflammatory Bowel Disease Program, University of Washington, Seattle, Washington, USA
| | - Matthew Pennington
- Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, Washington, USA
| | - David Lewis
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Mark Muzi
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Shirley Rene
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Jean Lee
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Tot Bui Nguyen
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
| | - Vineet Kumar
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
| | - Kazuya Ishida
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.,Pharmacokinetics and Drug Metabolism, Amgen, Cambridge, Massachusetts, USA
| | - Laigao Chen
- Early Clinical Development, Worldwide Research and Development, Pfizer Inc., Cambridge, Massachusetts, USA
| | - Xiaoyan Chu
- Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey, USA
| | - Yurong Lai
- Department of Drug Metabolism, Gilead Sciences, Inc., Foster City, California, USA
| | - Laurent Salphati
- Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California, USA
| | - Cornelis E C A Hop
- Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California, USA
| | - Guangqing Xiao
- Drug Metabolism and Pharmacokinetics, Biogen, Cambridge, Massachusetts, USA.,Department of Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA
| | - Mingxiang Liao
- Department of Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA
| | - Jashvant D Unadkat
- Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
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Kowalsky SJ, Zenati MS, Dhir M, Schaefer EG, Dopsovic A, Lee KK, Hogg ME, Zeh HJ, Vollmer CM, Zureikat AH. Postoperative narcotic use is associated with development of clinically relevant pancreatic fistulas after distal pancreatectomy. Surgery 2018; 163:747-752. [DOI: 10.1016/j.surg.2017.10.042] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 10/02/2017] [Accepted: 10/24/2017] [Indexed: 02/08/2023]
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Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr 2018; 66:159-176. [PMID: 29280782 PMCID: PMC5755713 DOI: 10.1097/mpg.0000000000001715] [Citation(s) in RCA: 149] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. CONCLUSIONS This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.
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Imam MZ, Kuo A, Ghassabian S, Smith MT. Progress in understanding mechanisms of opioid-induced gastrointestinal adverse effects and respiratory depression. Neuropharmacology 2017; 131:238-255. [PMID: 29273520 DOI: 10.1016/j.neuropharm.2017.12.032] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 12/18/2017] [Accepted: 12/19/2017] [Indexed: 02/06/2023]
Abstract
Opioids evoke analgesia through activation of opioid receptors (predominantly the μ opioid receptor) in the central nervous system. Opioid receptors are abundant in multiple regions of the central nervous system and the peripheral nervous system including enteric neurons. Opioid-related adverse effects such as constipation, nausea, and vomiting pose challenges for compliance and continuation of the therapy for chronic pain management. In the post-operative setting opioid-induced depression of respiration can be fatal. These critical limitations warrant a better understanding of their underpinning cellular and molecular mechanisms to inform the design of novel opioid analgesic molecules that are devoid of these unwanted side-effects. Research efforts on opioid receptor signalling in the past decade suggest that differential signalling pathways and downstream molecules preferentially mediate distinct pharmacological effects. Additionally, interaction among opioid receptors and, between opioid receptor and non-opioid receptors to form signalling complexes shows that opioid-induced receptor signalling is potentially more complicated than previously thought. This complexity provides an opportunity to identify and probe relationships between selective signalling pathway specificity and in vivo production of opioid-related adverse effects. In this review, we focus on current knowledge of the mechanisms thought to transduce opioid-induced gastrointestinal adverse effects (constipation, nausea, vomiting) and respiratory depression.
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Affiliation(s)
- Mohammad Zafar Imam
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia; UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Andy Kuo
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Sussan Ghassabian
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Maree T Smith
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia; School of Pharmacy, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia.
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Barshop K, Staller K. Eluxadoline in irritable bowel syndrome with diarrhea: rationale, evidence and place in therapy. Ther Adv Chronic Dis 2017; 8:153-160. [PMID: 29090081 PMCID: PMC5638229 DOI: 10.1177/2040622317714389] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 05/17/2017] [Indexed: 12/31/2022] Open
Abstract
Irritable bowel syndrome (IBS) is the most common gastrointestinal (GI) disorder worldwide, however treatment options for diarrhea-predominant IBS (IBS-D) remain limited. Eluxadoline, a µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, was recently approved for the treatment of IBS-D. A novel compound first described in 2008, eluxadoline was shown to normalize GI transit, with a subsequent phase I demonstrating its safety and tolerability in healthy adults. In 2016, two randomized, double-blind, placebo-controlled phase III trials studying eluxadoline use at 75 mg and 100 mg twice daily over 26 weeks demonstrated a significant improvement in stool consistency and many global symptoms of IBS. However, the data did not demonstrate a significant advantage over placebo using the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) endpoints for abdominal pain. Safety and tolerability data, pooled from both phase II and III studies, suggest that eluxadoline is generally well tolerated with the most common adverse events (AEs) occurring in approximately 3-8% of patients and included nausea, constipation, and abdominal pain. The most common serious adverse event (SAE) is pancreatitis, which had a 0.4% incidence. Recent US FDA reports reporting severe pancreatitis and sphincter of Oddi dysfunction after short-term use of eluxadoline in patients without a gallbladder has added a history of cholecystectomy as an important contraindication. Eluxadoline is also contraindicated in patients with a history of biliary duct obstruction, sphincter of Oddi dysfunction, active alcohol abuse, history of pancreatitis or known pancreatic duct obstruction, severe hepatic impairment, severe or chronic constipation, or known mechanical gastrointestinal obstruction. As a new drug to enter the IBS-D market, the place of eluxadoline in the hierarchy of IBS treatments is still to be determined. In this article, we review the development and clinical trial data behind the approval of eluxadoline with a focus on safety data and its use in clinical practice.
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Affiliation(s)
- Kenneth Barshop
- Department of Internal Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - Kyle Staller
- Division of Gastroenterology, Center for Neurointestinal Health, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
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Poulsen JL, Brock C, Grønlund D, Liao D, Gregersen H, Krogh K, Drewes AM. Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350. Dig Dis Sci 2017; 62:3156-3166. [PMID: 28986667 DOI: 10.1007/s10620-017-4784-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 09/27/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. AIMS To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. METHODS A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. RESULTS Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). CONCLUSION Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.
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Affiliation(s)
- Jakob Lykke Poulsen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000, Aalborg, Denmark.,Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
| | - Debbie Grønlund
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000, Aalborg, Denmark
| | - Donghua Liao
- GIOME Academia, Department of Clinical Medicine, Aarhus University, Nordre Ringgade 1, 8000, Aarhus, Denmark
| | - Hans Gregersen
- GIOME, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong
| | - Klaus Krogh
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000, Aalborg, Denmark. .,Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark.
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Camilleri M, Lembo A, Katzka DA. Opioids in Gastroenterology: Treating Adverse Effects and Creating Therapeutic Benefits. Clin Gastroenterol Hepatol 2017; 15:1338-1349. [PMID: 28529168 PMCID: PMC5565678 DOI: 10.1016/j.cgh.2017.05.014] [Citation(s) in RCA: 106] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Accepted: 05/02/2017] [Indexed: 02/07/2023]
Abstract
The use of opioid medications on both an acute and chronic basis is ubiquitous in the United States. As opioid receptors densely populate the gastrointestinal tract, symptoms and side effects can be expected in these patients. In the esophagus, dysmotility may result, manifesting with dysphagia and a syndrome indistinguishable from primary achalasia. In the stomach, a marked delay in gastric emptying may occur with postprandial nausea and early satiety. Postoperatively, particularly with abdominal surgery, opioid-induced ileus may ensue. In the colon, opioid-induced constipation is common. A unique syndrome termed narcotic bowel syndrome is characterized by chronic abdominal pain often accompanied by nausea and vomiting in the absence of other identifiable causes. With the recognition of the important role of opioids on gastrointestinal function, novel drugs have been developed that use this physiology. These medications include peripheral acting opioid agonists to treat opioid-induced constipation and combination agonist and antagonists used for diarrhea-predominant irritable bowel syndrome. This review summarizes the most recent data in these areas.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Anthony Lembo
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - David A Katzka
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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25
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Boothby LA, Wang LJ, Mayhew S, Chestnutt L. Academic Detailing of Meperidine at a Teaching Hospital. Hosp Pharm 2017. [DOI: 10.1177/001857870303800111] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Meperidine (Demerol) is an opiate analgesic that is not considered first-line therapy for most pain management indications because of concerns about its safety and efficacy. Inpatient data from a 417-bed community teaching hospital revealed high use of meperidine in oral, IM, and IV forms. A multifaceted academic detailing approach was employed to change prescribing behavior and decrease meperidine use. This approach included conducting two concurrent Medication Use Evaluations; Grand Rounds presentations for pharmacy staff, nurses, and medical residents; solicitation of opinion leaders; pocket and table-top cards; newsletter articles; and provision of pharmaceutical care. Comparing the number of meperidine doses dispensed per adjusted patient day before and after the intervention, use was reduced by 0.0966 doses per patient (P < 0.05: 95% CI, 0.0955 to 0.0977). The number of patients receiving meperidine was reduced by 2.43% (P < 0.05: 95% CI, 1.97 to 2.88). This translates into a relative reduction of 29.5% in patients receiving meperidine and a relative reduction of 31% in meperidine doses dispensed per patient after academic detailing initiatives vs before. Eighty-five percent of standard orders were changed to improve therapy; these changes included converting meperidine to morphine or hydromorphone, decreasing cumulative acetaminophen daily dosages, using controlled-release and immediate-release opioids for pain management when oral therapy was tolerated, and combining modalities with different mechanisms of action for synergy and to decrease potential adverse effects from larger dosages of single entities. Academic detailing of meperidine resulted in short-term changes in prescribing patterns and decreased meperidine use at this institution. Long-term implications for pain management have not yet been assessed.
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Affiliation(s)
- Lisa A Boothby
- Drug Information, Columbus Regional Drug Information Center, Columbus Regional Healthcare System
| | - Lih-Jen Wang
- Clinical Pharmacy Services, Department of Pharmacy, Columbus Regional Healthcare System
| | - Susan Mayhew
- Pharmacy Education, Department of Pharmacy, Columbus Regional Healthcare System
| | - Lynn Chestnutt
- Quality Management, Department of Pharmacy, Columbus Regional Healthcare System
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Safety of Eluxadoline in Patients with Irritable Bowel Syndrome with Diarrhea. Am J Gastroenterol 2017; 112:365-374. [PMID: 27922029 PMCID: PMC5318664 DOI: 10.1038/ajg.2016.542] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 10/01/2016] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Eluxadoline is a mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist, approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D). This analysis evaluated the safety and tolerability of eluxadoline 75 and 100 mg twice daily (BID) in one Phase 2 (IBS-2001) and two Phase 3 (IBS-3001 and IBS-3002) studies. METHODS Adults with IBS-D (Rome III criteria) were randomized to placebo or eluxadoline (75 or 100 mg) BID for 12 (IBS-2001), 26 (IBS-3002), or 52 (IBS-3001) weeks. Safety data were pooled. Adverse events (AEs) were assessed, with special focus on opioid-related AEs, including suspected sphincter of Oddi spasm (SOS) events. RESULTS 2,776 patients were included in the enrolled set; the safety set comprised 2,814 patients, based on actual treatments received. The most frequent AEs in the placebo and eluxadoline 75 and 100 mg groups were constipation (2.5, 7.4, and 8.1%, respectively) and nausea (5.0, 8.1, and 7.1%, respectively); discontinuation due to constipation was uncommon (0.3, 1.1, and 1.5%, respectively). Ten SOS events (10/1,839; 0.5%) occurred in eluxadoline-treated patients, manifesting as acute abdominal pain with elevated aminotransferases or lipase, or pancreatitis; all occurred in patients without a gallbladder. Eight of these events occurred with the higher dose of eluxadoline, within 1 week of initiation of therapy, and all resolved with eluxadoline discontinuation. There were five events independently adjudicated as pancreatitis not associated with SOS, three of which were associated with heavy alcohol use. CONCLUSIONS Eluxadoline was well tolerated in Phase 2 and 3 trials, with constipation and nausea the most common AEs. Consistent with the known adverse effects of opioid agonists, clinically apparent SOS events were observed in eluxadoline-treated patients. All occurred in patients without a gallbladder and the majority were observed in patients on the higher dose of eluxadoline, suggesting a possible association.
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Afghani E, Lo SK, Covington PS, Cash BD, Pandol SJ. Sphincter of Oddi Function and Risk Factors for Dysfunction. Front Nutr 2017; 4:1. [PMID: 28194398 PMCID: PMC5276812 DOI: 10.3389/fnut.2017.00001] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 01/10/2017] [Indexed: 12/14/2022] Open
Abstract
The sphincter of Oddi (SO) is a smooth muscle valve regulating the flow of biliary and pancreatic secretions into the duodenum, initially described in 1887 by the Italian anatomist, Ruggero Oddi. SO dysfunction (SOD) is a broad term referring to numerous biliary, pancreatic, and hepatic disorders resulting from spasms, strictures, and relaxation of this valve at inappropriate times. This review brings attention to various factors that may increase the risk of SOD, including but not limited to: cholecystectomy, opiates, and alcohol. Lack of proper recognition and treatment of SOD may be associated with clinical events, including pancreatitis and biliary symptoms with hepatic enzyme elevation. Pharmacologic and non-pharmacologic approaches are discussed to help recognize, prevent, and treat SOD. Future studies are needed to assess the treatment benefit of agents such as calcium-channel blockers, glyceryl trinitrate, or tricyclic antidepressants in patients with SOD.
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Affiliation(s)
| | - Simon K. Lo
- Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS. Eluxadoline for Irritable Bowel Syndrome with Diarrhea. N Engl J Med 2016; 374:242-53. [PMID: 26789872 DOI: 10.1056/nejmoa1505180] [Citation(s) in RCA: 221] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Effective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist), in patients with IBS with diarrhea. Methods We randomly assigned 2427 adults who had IBS with diarrhea to eluxadoline (at a dose of 75 mg or 100 mg) or placebo twice daily for 26 weeks (IBS-3002 trial) or 52 weeks (IBS-3001 trial). The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days from weeks 1 through 12 and from weeks 1 through 26. Results For weeks 1 through 12, more patients in the eluxadoline groups (75 mg and 100 mg) than in the placebo group reached the primary end point (IBS-3001 trial, 23.9% with the 75-mg dose and 25.1% with the 100-mg dose vs. 17.1% with placebo; P=0.01 and P=0.004, respectively; IBS-3002 trial, 28.9% and 29.6%, respectively, vs. 16.2%; P<0.001 for both comparisons). For weeks 1 through 26, the corresponding rates in IBS-3001 were 23.4% and 29.3% versus 19.0% (P=0.11 and P<0.001, respectively), and the corresponding rates in IBS-3002 were 30.4% and 32.7% versus 20.2% (P=0.001 and P<0.001, respectively). The most common adverse events associated with 75 mg of eluxadoline and 100 mg of eluxadoline, as compared with placebo, were nausea (8.1% and 7.5% vs. 5.1%), constipation (7.4% and 8.6% vs. 2.5%), and abdominal pain (5.8% and 7.2% vs. 4.1%). Pancreatitis developed in 5 (2 in the 75-mg group and 3 in the 100-mg group) of the 1666 patients in the safety population (0.3%). Conclusions Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women, with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily. (Funded by Furiex Pharmaceuticals, an affiliate of Allergan; IBS-3001 and IBS-3002 ClinicalTrials.gov numbers, NCT01553591 and NCT01553747 , respectively.).
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Affiliation(s)
- Anthony J Lembo
- From Harvard Medical School, Boston (A.J.L.); Geisel School of Medicine at Dartmouth, Hanover, NH (B.E.L.); Texas Tech University Health Sciences Center, El Paso (M.J.Z.); School of Medicine, Temple University, Philadelphia (R.S.); and Furiex Pharmaceuticals, Morrisville, NC (L.S.D., D.A.A., J.M.D., G.M., R.L., L.T., P.S.C.)
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Poulsen JL, Brock C, Olesen AE, Nilsson M, Drewes AM. Evolving paradigms in the treatment of opioid-induced bowel dysfunction. Therap Adv Gastroenterol 2015; 8:360-72. [PMID: 26557892 PMCID: PMC4622283 DOI: 10.1177/1756283x15589526] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.
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Affiliation(s)
- Jakob Lykke Poulsen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - Anne Estrup Olesen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - Matias Nilsson
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, DK-9000 Aalborg, Denmark
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Angelis CD, Marietti M, Bruno M, Pellicano R, Rizzetto M. Endoscopic ultrasound in common bile duct dilatation with normal liver enzymes. World J Gastrointest Endosc 2015; 7:799-805. [PMID: 26191344 PMCID: PMC4501970 DOI: 10.4253/wjge.v7.i8.799] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/23/2014] [Accepted: 05/27/2015] [Indexed: 02/05/2023] Open
Abstract
In recent years, the description of isolated bile duct dilatation has been increasingly observed in subjects with normal liver function tests and nonspecific abdominal symptoms, probably due to the widespread use of high-resolution imaging techniques. However, there is scant literature about the evolution of this condition and the impact of endoscopic ultrasound (EUS) in the diagnostic work up. When noninvasive imaging tests (transabdominal ultrasound, computed tomography or magnetic resonance cholangiopancreatography) fail to identify the cause of dilatation and clinical or biochemical alarm signs are absent, the probability of having biliary disease is considered low. In this setting, using EUS, the presence of pathologic findings (choledocholithiasis, strictures, chronic pancreatitis, ampullary or pancreatic tumors, cholangiocarcinoma), not always with a benign course, has been observed. The aim of this review has been to evaluate the prevalence of disease among non-jaundiced patients without signs of cytolysis and/or cholestasis and the assessment of EUS yield. Data point out to a promising role of EUS in the identification of a potential biliary pathology. EUS is a low invasive technique, with high accuracy, that could play a double cost-effective role: identifying pathologic conditions with dismal prognosis, in asymptomatic patients with negative prior imaging tests, and excluding pathologic conditions and further follow-up in healthy subjects.
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Turkmen S, Buyukhatipoglu H, Suner A, Apucu HG, Ulas T. Prior cholecystectomy predisposes to acute pancreatitis in codeine-prescribed patients. Int J Crit Illn Inj Sci 2015; 5:114-5. [PMID: 26157656 PMCID: PMC4477388 DOI: 10.4103/2229-5151.158416] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
In this paper, we report a case of drug-induced pancreatitis just after taking a pain pill including a low-dose combination of acetaminophen and codeine. Codeine-induced pancreatitis has been rarely reported, however, well-established. The proposed mechanism for codeine-induced pancreatitis is by increasing Oddi sphincter pressure. However, the clinically important point is that the codeine-induced pancreatitis is seen almost only in the cholecystectomized patients due to lacking of its reservoir capacity. Codeine is commonly used alone or in combination in pain medicine. Therefore, it is fairly important to question whether a patient underwent cholecystectomy when a physician decides to prescribe codeine-included preparations.
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Affiliation(s)
- Serdar Turkmen
- Department of Cardiology, Sanko University School of Medicine, Gaziantep, Turkey
| | - Hakan Buyukhatipoglu
- Department of Internal Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Ali Suner
- Department of Internal Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Haci Gokhan Apucu
- Department of Internal Medicine, Necip Fazil Metropolitan Hospital, Kahramanmaras, Turkey
| | - Turgay Ulas
- Department of Internal Medicine, Harran University School of Medicine, Sanliurfa, Turkey
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Abstract
Acute pancreatitis is most frequently of biliary or alcoholic origin and less frequently due to iatrogenic (ERCP, medication) or metabolic causes. Diagnosis is usually based on abdominal pain and elevation of serum lipase to more than three-times the normal limit. Acute pancreatitis can either resolve quickly following an oedematous swelling or present as a severe necrotizing form. A major risk is the systemic inflammatory response syndrome (SIRS), which can cause multi-organ failure. Prediction of disease course is initially difficult, thus necessitating immediate therapy and regular re-evaluation. In order to prove or exclude biliary genesis, abdominal ultrasonography should first be performed and endoscopic ultrasound may also be required. Primary therapy includes rapid and correctly dosed fluid substitution. Biliary pancreatitis requires causal treatment. In the case of cholangitis, stone extraction must be performed immediately; in the absence of cholangitis, it might be advisable to wait for spontaneous stone clearance. Timely cholecystectomy is necessary in all cases of biliary pancreatitis.
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Tabner A, Johnson G. Codeine: An Under-Recognized and Easily Treated Cause of Acute Abdominal Pain. Am J Emerg Med 2015; 33:1847.e1-2. [PMID: 25983269 DOI: 10.1016/j.ajem.2015.04.082] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Accepted: 04/11/2015] [Indexed: 11/30/2022] Open
Abstract
We present 2 cases of acute abdominal pain secondary to oral codeine that resolved after the administration of intravenous naloxone.
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Affiliation(s)
- Andrew Tabner
- Emergency Department, Royal Derby Hospital, Derby DE22 3NE, United Kingdom.
| | - Graham Johnson
- Emergency Department, Royal Derby Hospital, Derby DE22 3NE, United Kingdom
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Poulsen JL, Brock C, Olesen AE, Nilsson M, Drewes AM. Clinical potential of naloxegol in the management of opioid-induced bowel dysfunction. Clin Exp Gastroenterol 2014; 7:345-58. [PMID: 25278772 PMCID: PMC4179399 DOI: 10.2147/ceg.s52097] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Opioid-induced bowel dysfunction (OIBD) is a burdensome condition which limits the therapeutic benefit of analgesia. It affects the entire gastrointestinal tract, predominantly by activating opioid receptors in the enteric nervous system, resulting in a wide range of symptoms, such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation. The majority of studies evaluating OIBD focus on constipation experienced in approximately 60% of patients. Nevertheless, other presentations of OIBD seem to be equally frequent. Furthermore, laxative treatment is often insufficient, which in many patients results in decreased quality of life and discontinuation of opioid treatment. Novel mechanism-based pharmacological approaches targeting the gastrointestinal opioid receptors have been marketed recently and even more are in the pipeline. One strategy is prolonged release formulation of the opioid antagonist naloxone (which has limited systemic absorption) and oxycodone in a combined tablet. Another approach is peripherally acting, μ-opioid receptor antagonists (PAMORAs) that selectively target μ-opioid receptors in the gastrointestinal tract. However, in Europe the only PAMORA approved for OIBD is the subcutaneously administered methylnaltrexone. Alvimopan is an oral PAMORA, but only approved in the US for postoperative ileus in hospitalized patients. Finally, naloxegol is a novel, oral PAMORA expected to be approved soon. In this review, the prevalence and pathophysiology of OIBD is presented. As PAMORAs seem to be a promising approach, their potential effect is reviewed with special focus on naloxegol's pharmacological properties, data on safety, efficacy, and patient-focused perspectives. In conclusion, as naloxegol is administered orally once daily, has proven efficacious compared to placebo, has an acceptable safety profile, and can be used as add-on to existing pain treatment, it is a welcoming addition to the targeted treatment possibilities for OIBD.
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Affiliation(s)
- Jakob Lykke Poulsen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark ; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - Anne Estrup Olesen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark ; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - Matias Nilsson
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark ; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Abstract
Although the incidence of acute pancreatitis among children is less than that in adults, the physical and psychosocial impact on children and their families can be overwhelming. Pancreatitis is manifested as pain accompanied by a host of other complex issues. These issues are manifested more markedly when the patient has additional concomitant diagnoses. Pain management, liver function tests, amylase and lipase levels, endocrine and exocrine functionality, and recognition of systemic inflammation are especially important. Management after discharge from the hospital is often an ongoing stress for these patients and families, and multiple admissions to the intensive care unit may be necessary for feeding and pain complications. Presented in the context of an actual clinical case at a 500-bed tertiary care pediatric hospital, this patient’s scenario illustrates the importance of ensuring adequate nutrition, maintaining hydration, providing appropriate pain management, and preventing infection and thromboembolic events.
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Affiliation(s)
- Chris Kramer
- Chris Kramer is a registered nurse in the pediatric intensive care unit at Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
| | - Alvin Jeffery
- Alvin Jeffery is an education specialist in the Center for Professional Excellence/Education at Cincinnati Children’s Hospital Medical Center
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Zhou P, Li T, Su R, Gong Z. Effects of thienorphine on contraction of the guinea pig sphincter of Oddi, choledochus and gall bladder. Eur J Pharmacol 2014; 737:22-8. [PMID: 24830319 DOI: 10.1016/j.ejphar.2014.04.044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/17/2014] [Accepted: 04/17/2014] [Indexed: 02/07/2023]
Abstract
Opioid analgesics are widely believed to cause spasm of the bile duct sphincter and so impede bile flow. Thienorphine is a partial opioid agonist that is a good candidate for the treatment of opioid dependence; however, to date, no studies have reported the effects of thienorphine on the function of the biliary tract. This study examined the in vivo effects of thienorphine on the guinea pig isolated sphincter of Oddi, choledochus and gall bladder and on bile flow. The area under the curve (AUC) of isolated sphincter of Oddi was not influenced by thienorphine or buprenorphine, whereas morphine increased the AUC of the isolated sphincter of Oddi in a concentration-dependent manner. Thienorphine and buprenorphine concentration-dependently decreased the AUC of isolated choledochus, while morphine increased the AUC of isolated choledochus. Thienorphine had no effect on the contractile amplitude or basal tension of isolated gall bladder muscle strips. In contrast, buprenorphine and morphine increased the contractile basal tension of isolated gall bladder muscle strips in a concentration-dependent manner. Thienorphine (0.01-1.0mg/kg) had no significant inhibitory effect on bile flow. However, morphine (1.0-10mg/kg) and buprenorphine (1.0mg/kg) significantly inhibited bile flow. The maximum inhibition of bile flow by buprenorphine was 63.9±12.9% and by morphine was 74.1±11.3%. In summary, thienorphine has little influence on the guinea pig isolated sphincter of Oddi, choledochus and gall bladder or on bile flow, which may result in a lack of adverse biliary colic effects.
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Affiliation(s)
- Peilan Zhou
- Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing 100850, China.
| | - Tingting Li
- Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing 100850, China.
| | - Ruibin Su
- Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing 100850, China.
| | - Zehui Gong
- Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing 100850, China.
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Common bile duct dilatation in drug users with chronic hepatitis C is associated with current methadone use. J Addict Med 2014; 8:53-8. [PMID: 24394497 DOI: 10.1097/adm.0000000000000006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES Dilatation of the common bile duct (CBD) can be an ominous sign for malignancy of the pancreatobiliary tract; however, it has also been described as a presumably harmless side effect of opioid use. We investigated the prevalence and determinants of CBD dilatation among drug users receiving methadone maintenance therapy in the Netherlands. METHODS A cross-sectional study was conducted in a prospectively studied and well-defined cohort of drug users with chronic hepatitis C virus infection, attending the Public Health Service of Amsterdam, the Netherlands. Patients underwent abdominal ultrasonography as part of pretreatment screening. A multivariable logistic regression model was used to analyze potential demographic and drug use-related determinants of radiological CBD dilatation. RESULTS Between September 2004 and December 2011, 222 hepatitis C virus-infected drug users were evaluated. Dilatation of the CBD was found in 50 of 222 patients (22.5%), with a median diameter of 8.0 mm (interquartile range, 7.0 to 10.0; n = 43). Dilatation was associated with current use of methadone (adjusted odds ratio = 20.50; 95% confidence interval, 2.79 to 2.61 × 10(3)), independent of the current methadone dose, and with age per 10-year increase (adjusted odds ratio = 1.68; 95% confidence interval, 1.06 to 2.71). Regular use of heroin in the 6 months before ultrasonography was not found to be associated with dilatation. CONCLUSIONS Dilatation of the CBD is common in drug users under methadone treatment and seems to be a harmless side effect of opioid agonists.
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Sharma SS, Ram S, Maharshi S, Shankar V, Katiyar P, Jhajharia A, Sardava V, Bhardwaj H. Pancreato-biliary Endoscopic Ultrasound in Opium Addicts Presenting with Abdominal Pain. Endosc Ultrasound 2013; 2:204-207. [PMID: 24949397 PMCID: PMC4062278 DOI: 10.4103/2303-9027.121247] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Accepted: 08/29/2013] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE Asymptomatic dilatation of bile duct and symptomatic sphincter of Oddi dysfunction have been reported in opium addicts. Except one case report, there is no report in the literature on endoscopic ultrasound (EUS) study of pancreato-biliary system in opium addicts. The aim of the present study was to report the EUS features of pancreato-biliary system in opium addicts presenting with abdominal pain. PATIENTS AND METHODS A total of 15 opium addicts presenting with upper abdominal pain and dilated common bile duct (CBD) and or pancreatic duct (PD) on abdominal ultrasound were included in this study. EUS findings of pancreato-biliary system were analyzed in these patients. RESULTS All the 15 patients were males (mean age 53.3 years) presented with upper abdominal pain. Mean duration of opium addiction was 20.1 years. On EUS CBD was dilated in all the patients while PD was dilated in six patients. Gall bladder, liver and pancreatic parenchyma was normal in all these patients. Surface area of papilla of Vater (SPV) was increased in 12 patients. CONCLUSION Opium addiction causes obstruction at ampulla and produces dilatation of bile duct and PD. Bile duct dilatation was seen in all the patients while PD dilatation was seen in few patients. Increase in SPV was a peculiar finding and appears to be as a result of direct effect of opium on ampulla.
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Affiliation(s)
- Shyam Sundar Sharma
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
| | - Seva Ram
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
| | - Sudhir Maharshi
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
| | - Vijay Shankar
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
| | - Prashant Katiyar
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
| | - Ashok Jhajharia
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
| | - Vimal Sardava
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
| | - Hemendra Bhardwaj
- Department of Gastroenterology, S.M.S. Medical College, Jaipur, Rajasthan, India
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Determinants of second-order bile duct visualization at CT cholangiography in potential living liver donors. AJR Am J Roentgenol 2013; 200:1028-33. [PMID: 23617485 DOI: 10.2214/ajr.11.8364] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE The purpose of this article is to investigate the determinants of second-order bile duct visualization at CT cholangiography in living potential liver donors. MATERIALS AND METHODS We retrospectively identified 143 potential living liver donors (83 men and 60 women; mean age, 37 years) evaluated with CT cholangiography, which included a slow infusion of iodipamide meglumine with CT acquisition 15 minutes after biliary contrast agent administration. Two readers independently scored the visualization of the second-order bile duct branches on a previously established 4-point scale (0 = not seen, 1 = faintly seen, 2 = well seen, and 3 = excellent visualization). Multivariate analysis was used to investigate the correlation between visualization scores and potential determinants of second-order bile duct opacification, specifically age, body mass index, creatinine level, total and direct bilirubin levels, alkaline phosphatase level, aspartate aminotransferase level, alanine aminotransferase level, patient maximum linear width, CT noise, and hepatosplenic attenuation difference at unenhanced CT. RESULTS The mean (± SD) second-order bile duct visualization scores were 2.35 ± 0.66 and 2.55 ± 0.60 for readers 1 and 2, respectively. In the multivariate analysis, the only independent predictors of reduced second-order bile duct visualization were higher alkaline phosphatase level (p = 0.01) and higher CT noise (p = 0.02). CONCLUSION Higher serum alkaline phosphatase level and higher CT noise in potential living liver donors indicate a higher risk of poor second-order bile duct visualization at CT cholangiography.
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Malviya A, Negi N, Mandora M, Yadav JK. Perioperative status and complications in opium addicts in Western rajasthan. Indian J Surg 2012; 73:346-51. [PMID: 23024539 DOI: 10.1007/s12262-011-0324-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2010] [Accepted: 03/23/2011] [Indexed: 11/26/2022] Open
Abstract
Opium addiction is rampant in Western Rajasthan and probably has the highest number of opium addicts in the world. The study envisages upon the presentation, diagnosis and various postoperative complications in surgically ill opium addicts vis-à-vis non addicts. The study is purported to benefit clinicians dealing with opium addict patients. The prospective cohort study was conducted at Mahatma Gandhi Hospital, Jodhpur between December 2004 and February 2006 and included cohorts of 71 opium addict and 50 non-addict patients admitted in various surgical wards. The study focused on presentation and the post-surgical complications encountered in these patients vis-à-vis others. The results thus obtained were evaluated statistically (mean±SD, SEM, two tailed t test, chi-square test), p value of <0.05 was considered as significant. A thorough comparative analysis revealed that opium addict patients had a significantly higher incidence of postoperative respiratory, cardiovascular, systemic and local complications. The requirement of analgesics and duration of hospital stay were also significantly higher as compared to control group. The work concludes that opium addicts suffer a much higher degree of postoperative morbidity as compared to non-addicts.
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Affiliation(s)
- Ajay Malviya
- Department of Surgery, Dr. S.N. Medical College, Jodhpur, Rajasthan India
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Cruz-Santamaría DM, Taxonera C, Giner M. Update on pathogenesis and clinical management of acute pancreatitis. World J Gastrointest Pathophysiol 2012; 3:60-70. [PMID: 22737590 PMCID: PMC3382704 DOI: 10.4291/wjgp.v3.i3.60] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2011] [Revised: 05/22/2012] [Accepted: 06/12/2012] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP), defined as the acute nonbacterial inflammatory condition of the pancreas, is derived from the early activation of digestive enzymes found inside the acinar cells, with variable compromise of the gland itself, nearby tissues and other organs. So, it is an event that begins with pancreatic injury, elicits an acute inflammatory response, encompasses a variety of complications and generally resolves over time. Different conditions are known to induce this disorder, although the innermost mechanisms and how they act to develop the disease are still unknown. We summarize some well established aspects. A phase sequence has been proposed: etiology factors generate other conditions inside acinar cells that favor the AP development with some systemic events; genetic factors could be involved as susceptibility and modifying elements. AP is a disease with extremely different clinical expressions. Most patients suffer a mild and limited disease, but about one fifth of cases develop multi organ failure, accompanied by high mortality. This great variability in presentation, clinical course and complications has given rise to the confusion related to AP related terminology. However, consensus meetings have provided uniform definitions, including the severity of the illness. The clinical management is mainly based on the disease´s severity and must be directed to correct the underlying predisposing factors and control the inflammatory process itself. The first step is to determine if it is mild or severe. We review the principal aspects to be considered in this treatment, as reflected in several clinical practice guidelines. For the last 25 years, there has been a global increase in incidence of AP, along with many advances in diagnosis and treatment. However, progress in knowledge of its pathogenesis is scarce.
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Sommer CM, Schwarzwaelder CB, Stiller W, Schindera ST, Heye T, Stampfl U, Bellemann N, Holzschuh M, Schmidt J, Weitz J, Grenacher L, Kauczor HU, Radeleff BA. Dual-energy CT-cholangiography in potential donors for living-related liver transplantation: improved biliary visualization by intravenous morphine co-medication. Eur J Radiol 2011; 81:2007-13. [PMID: 21696902 DOI: 10.1016/j.ejrad.2011.05.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2011] [Revised: 05/10/2011] [Accepted: 05/13/2011] [Indexed: 11/24/2022]
Abstract
PURPOSE To prospectively evaluate whether intravenous morphine co-medication improves bile duct visualization of dual-energy CT-cholangiography. MATERIALS AND METHODS Forty potential donors for living-related liver transplantation underwent CT-cholangiography with infusion of a hepatobiliary contrast agent over 40 min. Twenty minutes after the beginning of the contrast agent infusion, either normal saline (n=20 patients; control group [CG]) or morphine sulfate (n=20 patients; morphine group [MG]) was injected. Forty-five minutes after initiation of the contrast agent, a dual-energy CT acquisition of the liver was performed. Applying dual-energy post-processing, pure iodine images were generated. Primary study goals were determination of bile duct diameters and visualization scores (on a scale of 0 to 3: 0--not visualized; 3--excellent visualization). RESULTS Bile duct visualization scores for second-order and third-order branch ducts were significantly higher in the MG compared to the CG (2.9±0.1 versus 2.6±0.2 [P<0.001] and 2.7±0.3 versus 2.1±0.6 [P<0.01], respectively). Bile duct diameters for the common duct and main ducts were significantly higher in the MG compared to the CG (5.9±1.3 mm versus 4.9±1.3 mm [P<0.05] and 3.7±1.3 mm versus 2.6±0.5 mm [P<0.01], respectively). CONCLUSION Intravenous morphine co-medication significantly improved biliary visualization on dual-energy CT-cholangiography in potential donors for living-related liver transplantation.
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Affiliation(s)
- C M Sommer
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany.
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Puylaert M, Kapural L, Van Zundert J, Peek D, Lataster A, Mekhail N, van Kleef M, Keulemans YCA. 26. Pain in chronic pancreatitis. Pain Pract 2011; 11:492-505. [PMID: 21676159 DOI: 10.1111/j.1533-2500.2011.00474.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic pancreatitis is defined as a progressive inflammatory response of the pancreas that has lead to irreversible morphological changes of the parenchyma (fibrosis, loss of acini and islets of Langerhans, and formation of pancreatic stones) as well as of the pancreatic duct (stenosis and pancreatic stones). Pain is one of the most important symptoms of chronic pancreatitis. The pathogenesis of this pain can only partly be explained and it is therefore often difficult to treat this symptom. The management of pain induced by chronic pancreatitis starts with lifestyle changes and analgesics. For the pharmacological management, the three-step ladder of the World Health Organization extended with the use of co-analgesics is followed. Interventional pain management may consist of radiofrequency treatment of the nervi splanchnici, spinal cord stimulation, endoscopic stenting or stone extraction possibly in combination with lithotripsy, and surgery. To date, there are no randomized controlled trials supporting the efficacy of radiofrequency and spinal cord stimulation. The large published series reports justify a recommendation to consider these treatment options. Radiofrequency treatment, being less invasive than spinal cord stimulation, could be tested prior to considering spinal cord stimulation. There are several other treatment possibilities such as endoscopic or surgical treatment, pancreatic enzyme supplementation and administration of octreotide and antioxidants. All may have a role in the management of pain induced by chronic pancreatitis.
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Affiliation(s)
- Martine Puylaert
- Department of Anesthesiology and Multidisciplinary Pain Centre, Ziekenhuis Oost-Limburg, Genk, Belgium
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The Effects of Morphine–Neostigmine and Secretin Provocation on Pancreaticobiliary Morphology in Healthy Subjects: A Randomized, Double-blind Crossover Study Using Serial MRCP. World J Surg 2011; 35:2102-9. [DOI: 10.1007/s00268-011-1162-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Park S, Choi GS, Jung J, Cho G, Shin E, Lim C, Kim H, Song OP. Clinical Efficacy of Pretransplant Magnetic Resonance Cholangiography of Donor for Living Donor Liver Transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2010. [DOI: 10.4285/jkstn.2010.24.4.311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- SeungWan Park
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
| | - Gyu-seong Choi
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
| | - JunChul Jung
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
| | - Gyuseok Cho
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
| | - EungJin Shin
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
| | - ChulWan Lim
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
| | - HyungChul Kim
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
| | - Ok-Pyung Song
- Department of Surgery, Sunchunhyang University Bucheon Hospital, Suncheonhyang University College of Medicine, Bucheon, Korea
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Takemura Y, Furuta S, Hirayama S, Miyashita K, Imai S, Narita M, Kuzumaki N, Tsukiyama Y, Yamazaki M, Suzuki T, Narita M. Upregulation of bradykinin receptors is implicated in the pain associated with caerulein-induced acute pancreatitis. Synapse 2010; 65:608-16. [DOI: 10.1002/syn.20880] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2010] [Accepted: 09/23/2010] [Indexed: 01/01/2023]
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Koo HC, Moon JH, Choi HJ, Hwang KH, Maeng HJ, Kim HK, Park JK, Hong SJ, Cheon YK, Cho YD, Lee JS, Lee MS. Effect of transdermal fentanyl patches on the motility of the sphincter of oddi. Gut Liver 2010; 4:368-72. [PMID: 20981215 DOI: 10.5009/gnl.2010.4.3.368] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2010] [Accepted: 03/31/2010] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND/AIMS Pain is one of the most troublesome symptoms of pancreatitis. Transdermal fentanyl patches (TFPs) are long-acting analgesics with a reduced risk of dependency. This prospective study evaluated the effect of TFPs on sphincter of Oddi (SO) motility for the management of pain in pancreatitis. METHODS SO manometry (SOM) was performed using triple-lumen catheters anterogradely inserted through the percutaneous transhepatic route during cholangioscopy in 16 patients. The basal pressure, amplitude, and frequency of the SO were assessed before and after applying a TFP at 24 hour at doses of 25 and 12.5µg/hr, respectively. RESULTS Two of 16 patients receiving a 25µg/hr. TFP were excluded because of adverse side effects (headache and/or nausea). The mean basal pressure, amplitude, and frequency of SOM did not change significantly in the 25µg/hr TFP group (n=4 patients). Parameters of SO function also did not significantly change in the 12.5µg/hr TFP group (n=11 patients). CONCLUSIONS TFPs below a dose of 25µg/hr may not affect the motility of the SO. Administration of TFPs at lower dosages seems to be a safe analgesic treatment for the pain control of patients with pancreatitis without affecting the function of the SO.
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Affiliation(s)
- Hyun Cheol Koo
- Digestive Disease Center, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon and Seoul, Korea
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Rezaee A, Narouie B, Ghasemi-Rad M, Nosair E, Mohebi F, Sharareh Sanei Sistani. Is Opioid Addiction a Sufficient Predicting Factor for Common Bile Duct Dilatation? A Sonographic Study. JOURNAL OF DIAGNOSTIC MEDICAL SONOGRAPHY 2010; 26:137-142. [DOI: 10.1177/8756479310366470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/25/2024]
Abstract
In the absence of hepatobiliary symptoms, opioid consumption has been shown to cause dilatation of the common bile duct (CBD). The main objective of this study was to measure with sonography CBD diameters in opioid addicts as compared with nonaddicts. The research was done on 208 individuals; 104 were opioid addicts using various routes of administration (inhalation, oral, or intravenous), and 104 had no history of addiction (control group). All patients underwent abdominopelvic sonography, and the internal diameters of the proximal part of the CBD were recorded. The average CBD diameter in the control group was 4.13 ± 1.14 mm, which significantly increased to 8.16 ± 2.54 mm in the case group. A significant increase in the average diameter of CBD in the case group with the oral route was 10.7 ± 2.26 mm, compared with 7.5 ± 1.64 mm and 7.6 ± 3.05 mm, respectively, for those using inhalation and intravenous routes. The diameter of CBD was age dependent. The dilatation of the CBD detected by sonography occurring in opioid addicts in all age groups was attributed principally to the effect of opioids. Oral administration of opioid caused the highest dilatation effect on CBD.
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Affiliation(s)
- Ahmad Rezaee
- Zahedan University of Medical Sciences, Zahedan, Iran
| | - Behzad Narouie
- Ali-ebne-Abitaleb Hospital, Zahedan University of Medical Sciences, Iran,
| | | | - Emad Nosair
- University of Sharjah, Sharjah, United Arab Emirates
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Muddana V, Whitcomb DC, Papachristou GI. Current management and novel insights in acute pancreatitis. Expert Rev Gastroenterol Hepatol 2009; 3:435-44. [PMID: 19673630 DOI: 10.1586/egh.09.27] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Acute pancreatitis (AP) is a common and potentially lethal acute inflammatory process. Approximately 10-20% of patients develop a severe course and suffer systemic inflammatory response and/or pancreatic necrosis (PNec). To date, there is no single biomarker proven to perform better than clinical judgment in predicting severe AP. The available prognostic clinical scoring systems are used primarily for research purposes. Management of AP is limited to supportive care and treatment of complications when they develop. Patients with mild AP require regular ward admission, fluid administration, bowel rest and pain management. Patients with signs of severe AP should be identified early and admitted promptly to an intensive-care unit. Nutrition support via nasojejunal feedings should be initiated. Sterile PNec is managed conservatively. Infected PNec requires minimally invasive debridement via endoscopic or surgical approaches. The lack of scientific advancements in the management of AP reflects the limited understanding of the early pathogenetic mechanisms and our moderate-to-poor ability to predict severe course at the time of admission.
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Affiliation(s)
- Venkata Muddana
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PA 15219, USA
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