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Wu D, Bai X, Lee P, Yang Y, Windsor J, Qian J. A systematic review of NSAIDs treatment for acute pancreatitis in animal studies and clinical trials. Clin Res Hepatol Gastroenterol 2021; 44S:100002. [PMID: 33602483 DOI: 10.1016/j.clirex.2019.100002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 08/08/2019] [Accepted: 08/26/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently given to patients with acute pancreatitis (AP) for controlling pain, but their efficacy in treating AP, particularly in reducing systemic complications, remains unclear. AIM The aim of our study was to evaluate the efficacy of NSAIDs in treating AP and its systematic complications. METHODS Two independent reviewers screened articles from MEDLINE, Embase and Cochrane and scored the quality of each study according to the CAMARADES 10-item quality checklist or the Jadad scale. Five endpoints were chosen to evaluate the effect of NSAIDs in animal studies: amylase and lipase levels, proinflammatory cytokines, oxidative damage, histopathological changes, and mortality rate. Meanwhile, in clinical studies, endpoints, such as proinflammatory cytokines, pain relief, systematic complications, mortality, and adverse events were used. RESULTS A total of 36 studies out of 17,845 were identified and included. Of these 36 studies, only 5 were clinical trials involving 580 patients, and the remaining 31 were animal studies with 1623 rats or mice. 24 studies focused on the treatment of AP with NSAIDs and 12 on AP-associated systematic complications. Both preclinical and clinical studies showed that NSAIDs may have beneficial effects against AP-related injuries. 9 of the 14 preclinical studies stated that NSAIDs reduced the serum amylase level significantly, and 6 of 7 showed that NSAIDs lowered the lipase level markedly. 17 experimental studies all demonstrated that NSAIDs reduced the inflammation. Histopathological examinations indicated that NSAIDs significantly improved the histopathological damages. Similarly, clinical evidence showed that NSAIDs are effective in suppressing proinflammatory cytokines, relieving pain, ameliorating systematic complications and reducing mortality. In the included 5 clinical studies, serious adverse events associated with NSAIDs were rarely reported. CONCLUSION This systematic review shows that NSAIDs are a potential treatment for AP-related injuries based on the current preclinical and clinical evidences.
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Affiliation(s)
- Dong Wu
- Department of Gastroenterology, Translational Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Xiaoyin Bai
- Department of Gastroenterology, Translational Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Peter Lee
- Division of Gastroenterology, Department of Medicine, Hospital of the University of Pennsylvania, PA, USA
| | - Yingyun Yang
- Department of Gastroenterology, Translational Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - John Windsor
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Park Road, Auckland, New Zealand
| | - Jiaming Qian
- Department of Gastroenterology, Translational Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
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Chai XQ, Ma J, Xie YH, Wang D, Chen KZ. Flurbiprofen axetil increases arterial oxygen partial pressure by decreasing intrapulmonary shunt in patients undergoing one-lung ventilation. J Anesth 2015; 29:881-6. [PMID: 26272250 DOI: 10.1007/s00540-015-2060-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 07/20/2015] [Indexed: 11/24/2022]
Abstract
PURPOSES In the present study, we investigated whether flurbiprofen axetil (FA) alleviates hypoxemia during one-lung ventilation (OLV) by reducing the pulmonary shunt/total perfusion (Q s/Q t) ratio, and examined the relationship between the Q s/Q t ratio and the thromboxane B2 (TXB2)/6-keto-prostaglandin F1α (6-K-PGF1α) ratio. METHODS Sixty patients undergoing esophageal resection for carcinoma were randomly assigned to groups F and C (n = 30 for each group). FA and placebo were administered i.v. 15 min before skin incision in groups F and C, respectively. The partial pressure of arterial oxygen (PaO2) was measured and the Q s/Q t ratio was calculated. Serum TXB2, 6-K-PGF1α, and endothelin (ET) were measured by radioimmunoassay. The relationship between TXB2/6-K-PGF1α and Q s/Q t was investigated. RESULTS Compared with group C, PaO2 was higher and the Q s/Q t ratio was lower during OLV in group F (P < 0.05). After treatment with FA, both serum TXB2 and 6-K-PGF1α decreased significantly (P < 0.05) but the TXB2/6-K-PGF1α ratio increased significantly (P < 0.01). Increases in the TXB2/6-K-PGF1α ratio were correlated with reductions in the Q s/Q t ratio during OLV in group F (r = -0.766, P < 0.01). There was no significant difference in serum ET between groups F and C. CONCLUSIONS Treatment with FA reduced the Q s/Q t ratio and further increased the PaO2 level during OLV, possibly due to upregulation of the vasoactive agent TXB2/6-K-PGF1α ratio.
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Affiliation(s)
- Xiao-Qing Chai
- Department of Anesthesiology, Affiliated Provincial Hospital of Anhui Medical University, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
| | - Jun Ma
- Department of Anesthesiology, Affiliated Provincial Hospital of Anhui Medical University, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China
| | - Yan-Hu Xie
- Department of Anesthesiology, Affiliated Provincial Hospital of Anhui Medical University, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China
| | - Di Wang
- Department of Anesthesiology, Affiliated Provincial Hospital of Anhui Medical University, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China
| | - Kun-Zhou Chen
- Department of Anesthesiology, Affiliated Provincial Hospital of Anhui Medical University, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China
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Pezzilli R, Morselli-Labate AM, Corinaldesi R. NSAIDs and Acute Pancreatitis: A Systematic Review. Pharmaceuticals (Basel) 2010; 3:558-571. [PMID: 27713268 PMCID: PMC4033969 DOI: 10.3390/ph3030558] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2010] [Revised: 02/11/2010] [Accepted: 03/09/2010] [Indexed: 12/14/2022] Open
Abstract
The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In addition, these drugs have also been used to prevent post-endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand, there are several reports indicating that NSAIDs may be the actual cause of acute pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text papers published in from January 1966 to November 2009 on the use of NSAIDs in acute pancreatitis were collected; the literature search was also supplemented by a review of the bibliographies of the papers evaluated. Thus, in this article, we will systematically review the current literature in order to better illustrate the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis and iii) their efficacy for pain relief in the acute illness of the pancreas.
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Affiliation(s)
- Raffaele Pezzilli
- Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
| | - Antonio Maria Morselli-Labate
- Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
| | - Roberto Corinaldesi
- Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
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Liu H, Li Y, Wang L, Chen H, Guan J, Zhou Z. Aggravation of acute pancreatitis by heparan sulfate in mice. Scand J Gastroenterol 2009; 44:626-32. [PMID: 19194821 DOI: 10.1080/00365520902745047] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Systemic inflammatory response syndrome (SIRS) is responsible for pancreatitis-associated mortality, but its initiating events are poorly understood. Possible candidates may be endogenous substances, which have previously been shown to mediate inflammatory responses. The aim of this study was to investigate whether SIRS could be exaggerated by heparan sulfate (HS) in acute pancreatitis (AP). MATERIAL AND METHODS AP was induced in mice by cerulein injection and HS was administered one hour after the final cerulein injection. The severity of pancreatitis was assessed by serum amylase activity, pancreatic edema, and pancreatic myeloperoxidase (MPO) activity. Systemic inflammation was evaluated by assessing lung injury and by measuring serum levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. Cytokine levels were also measured in pancreas and lung tissues. RESULTS HS did not worsen the pancreatic injury induced by cerulein. In contrast, HS exacerbated the systemic inflammation as measured by augmented lung MPO activity, increased lung TNF-alpha and IL-6 levels, and elevated serum IL-6 levels. CONCLUSIONS Our results indicate a potential role for HS in propagating pancreatic inflammation from a local process to a systemic response and thus suggest the possibility that blockade of HS might improve the outcome of SIRS in AP.
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Affiliation(s)
- Hongxiang Liu
- Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, China
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Intravenous flurbiprofen axetil accelerates restoration of bowel function after colorectal surgery. Can J Anaesth 2008; 55:414-22. [DOI: 10.1007/bf03016307] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Bhatia M, Sidhapuriwala JN, Sparatore A, Moore PK. Treatment with H2S-releasing diclofenac protects mice against acute pancreatitis-associated lung injury. Shock 2008; 29:84-88. [PMID: 17621252 DOI: 10.1097/shk.0b013e31806ec26] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Hydrogen sulfide (H(2)S) is a naturally occurring gas that has been shown to be a potent vasodilator. Diclofenac is a nonsteroidal anti-inflammatory drug and has been shown to have anti-inflammatory, analgesic, and antipyretic activity. ACS15 is an H(2)S-releasing derivative of diclofenac. Little is known about its effectiveness as an anti-inflammatory drug. In this report, we describe the effect of diclofenac and its H(2)S-releasing derivative on acute pancreatitis and associated lung injury in the mouse. Acute pancreatitis was induced in mice by hourly i.p. injections of cerulein. Diclofenac and ACS15 were administered either 1 hour before or 1 hour after starting cerulein injections, and the severity of acute pancreatitis and associated lung injury was assessed. The severity of acute pancreatitis was determined by hyperamylasemia, neutrophil sequestration in the pancreas (pancreatic myeloperoxidase activity), and pancreatic acinar cell injury/necrosis on histological examination of pancreas sections. The severity of acute pancreatitis-associated lung injury was assessed by neutrophil sequestration in the lungs (lung myeloperoxidase activity) and by histological examination of lung sections. ACS15, given prophylactically and therapeutically, significantly reduced lung inflammation without having any significant effect on pancreatic injury. These results suggest the usefulness of H(2)S-releasing nonsteroidal anti-inflammatory drugs as potential treatments for pancreatitis-associated lung injury.
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Affiliation(s)
- Madhav Bhatia
- Department of Pharmacology and Cardiovascular Biology Research Group, National University of Singapore.
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Zhang JX, Dang SC, Qu JG, Wang XQ. Ligustrazine alleviates acute renal injury in a rat model of acute necrotizing pancreatitis. World J Gastroenterol 2006; 12:7705-9. [PMID: 17171804 PMCID: PMC4088057 DOI: 10.3748/wjg.v12.i47.7705] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal injury in a rat model of acute necrotizing pancreatitis (ANP).
METHODS: A total of 192 rats were randomly divided into three groups: control (C group), ANP without treatment (P group), and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6, 12 h subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. T group was infused sodium taurocholate as above, and 0.6% ligustrazine was then administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr) concentrations were measured for the evaluation of renal function. The effects of ligustrazine on the severity of renal injury were assessed by renal function, TXA2/PGI2 and histopathological changes. Renal blood flow was determined by the radioactive microsphere technique (RMT).
RESULTS: Compared with control group, the renal blood flow in P group was decreased significantly. Serious renal and pancreatic damages were found in P group, the BUN and Cr levels were elevated significantly, and the ratio of TXA2 to PGI2 was increased at 2, 6 and 12 h. Compared with P group, the blood flow of kidney was elevated significantly at 6 and 12 h after induction of ANP, the renal and pancreatic damages were attenuated, and the BUN and Cr levels were decreased significantly, and the ratio of TXA2 to PGI2 was decreased at 6 and 12 h in T group.
CONCLUSION: Microcirculatory disorder (MCD) is an important factor for renal injury in ANP. Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and kidney.
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Affiliation(s)
- Jian-Xin Zhang
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
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Cosen-Binker LI, Binker MG, Cosen R, Negri G, Tiscornia O. Influence of nitric oxide-donating nonsteroidal anti-inflammatory drugs on the evolution of acute pancreatitis. Shock 2006; 25:190-203. [PMID: 16525359 DOI: 10.1097/01.shk.0000192122.91166.a8] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Microcirculatory disturbances and leukocyte activation are main events in the pathogenesis of acute pancreatitis (AP) that is characterized by inflammatory up-regulation. Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) regulate vascular function and mitigate inflammation. To investigate the influence of NO-NSAIDs on AP. AP was induced by the biliopancreatic duct outlet exclusion-closed duodenal loops model. Treatment with NO-flurbiprofen, NO-ibuprofen, NO-aspirin, or their parental drugs was done (i) 1 h before, (ii) 1 h after, (iii) 1 h before and 4 h after, or (iv) 4 h after surgery. The degree of severity was evaluated using biochemical and histopathological analyses. NO-NSAIDs given before and during the first hour of the noxia decreased blood levels of amylase, lipase, C-reactive protein, IL-6, IL-10, heat shock protein 72, prostaglandin E2 inactive metabolite, and 8-isoprostane, as well as pancreatic and lung myeloperoxidase and cyclooxygenase. Acinar and fat necrosis, hemorrhage, and leukocyte infiltrate were also reduced. The best protection was achieved when treatment was performed 1 h before and 4 h after triggering AP. NO-flurbiprofen was the most effective drug. AP severity was significantly ameliorated by NO-NSAIDs being the administration time essential to achieve optimal pancreatic protection that may result to be useful in the prevention of postendoscopic severe AP.
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Affiliation(s)
- Laura Iris Cosen-Binker
- Programa de Estudios Pancreáticos, Hospital de Clínicas, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
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