The online version of this article (doi:10.1186/1471-230X-14-102) contains supplementary material, which is available to authorized users.
Potential competing interest: The authors declare that they have no competing interest.
TS contributed to the study design, literature search and selection, data extraction and analysis, and writing the draft. YN, SS, and TN contributed to the literature search and selections, data extraction and analysis. All authors read and approved the final manuscript.
The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of protease inhibitors intravenously administered to prevent pancreatitis-associated complications.
We updated our previous meta-analysis with articles of randomized controlled trials published from January 1965 to March 2013 on the effectiveness of protease inhibitors for acute pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and Japana Centra Revuo Medicina was conducted. In addition, Internet-based registries (ClinicalTrials.gov, controlled-trials.com, UMIN, JMACCT, and JAPIC) were used to search for on-going clinical trials. Furthermore, references of review articles and previously published meta-analyses were handsearched. The main outcome of interest was the overall mortality rate from acute pancreatitis.
Seventeen trials were selected for analysis. Overall, protease inhibitors did not achieve a significant risk reduction in mortality (pooled risk difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10) did not show a significant effect of protease inhibitors to prevent death (pooled RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality) revealed a significant risk reduction.
The present meta-analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis.
Cavallini G, Frulloni L, Bassi C, Gabbrielli A, Castoldi L, Costamagna G, De Rai P, Di Carlo V, Falconi M, Pezzilli R, Uomo G, ProInf-AISP Study Group: Prospective multicentre survey on acute pancreatitis in Italy (ProInf-AISP): results on 1005 patients. Dig Liver Dis. 2004, 36: 205-211. 10.1016/j.dld.2003.11.027. CrossRefPubMed
Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA: Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev. 2010, 20: CD002837-
Brownfield E: Pain management. Making Healthcare Safer: A Critical Analysis of Patient Safety Practices. AHRQ Evidence Report/Technology Assessment Number 43. http://www.ahrq.gov/clinic/ptsafety/pdf/chap37.pdf,
Takeda K, Matsuno S, Sunamura M, Kakugawa Y: Continuous regional arterial infusion of protease inhibitor and antibiotics in acute necrotizing pancreatitis. Am J Surg. 1996, 17: 394-398. CrossRef
Takeda K, Yamauchi J, Shibuya K, Sunamura M, Mikami Y, Matsuno S: Benefit of continuous regional arterial infusion of protease inhibitor and antibiotic in the management of acute necrotizing pancreatitis. Pancreatol. 2001, 1: 668-673. 10.1159/000055879. CrossRef
Imaizumi H, Kida M, Nishimaki H, Okuno J, Kataoka Y, Kida Y, Soma K, Saigenji K: Efficacy of continuous regional arterial infusion of a protease inhibitor and antibiotic for severe acute pancreatitis in patients admitted to an intensive care unit. Pancreas. 2004, 28: 369-373. 10.1097/00006676-200405000-00003. CrossRefPubMed
Piaścik M, Rydzewska G, Milewski J, Olszewski S, Furmanek M, Walecki J, Gabryelewicz A: The results of severe acute pancreatitis treatment with continuous regional arterial infusion of protease inhibitor and antibiotic: a randomized controlled study. Pancreas. 2010, 39: 863-867. 10.1097/MPA.0b013e3181d37239. CrossRefPubMed
ClinicalTrials.gov: available from http://clinicaltrials.gov
Controlled-trials.com: available from http://www.controlled-trials.com
UMIN: Japan: University Hospital Medical Information Network, available from http://www.umin.ac.jp/ctr/index-j.htm
JMACCT: Japan Medical Association Clinical Trial Registry, available from https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS01/JMACTRS01.aspx?kbn=4
JAPIC: Japan Pharmaceutical Information Center. available from http://clinicaltrials.jp/user/cte_main.jsp
Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P, Montori V, Akl EA, Djulbegovic B, Falck-Ytter Y, Norris SL, Williams JW, Atkins D, Meerpohl J, Schünemann HJ: GRADE guidelines: 4. Tating the quality of evidence-study limitations (risk of bias). J Clin Epidemiol. 2011, 64: 407-415. 10.1016/j.jclinepi.2010.07.017. CrossRefPubMed
Light RJ, Pilemer DB: Summing up: the science of reviewing research. 1984, Cambridge, MA: Harvard University Press
Stata/SE 11 for Windows. 2009, College Station, Texas: Stata Corporation
Ryall RJ: Discussion on acute pancreatitis with a report on a clinical trial of trasylol. Anglo Ger Med Rev. 1966, 3: 274-283. PubMed
Baden H, Jordal K, Lund F, Zachariae F: A double-blind controlled clinical trial of Trasylol. Preliminary results in acute pancreatitis and in prophylaxis against postoperative pancreatitis. Acta Chir Scand Suppl. 1967, 378: 97-102. PubMed
Möller C, Stjernvall L: Clinical trial with Trasylol against acute pancreatitis. Ann Chir Gynaecol Fenn. 1969, 58: 296-299. PubMed
Baden H, Jordal K, Lund F, Zachariae F: Prophylactic and curative action of Trasylol in pancreatitis. A double-blind trial. Scand J Gastroenterol. 1969, 4: 291-295. PubMed
Death from acute pancreatitis. M.R.C. multicentre trial of glucagon and aprotinin. Lancet. 1977, 2: 632-635.
Gauthier A, Gillet M, Di Costanzo J, Camelot G, Maurin P, Sarles H: Controlled therapeutic trial of aprotinin and glucagon in acute pancreatitis. Gastroenterol Clin Biol. 1978, 2: 777-784. PubMed
Imrie CW: Medical treatment of acute pancreatitis. Gastroenterology. 1978, 75: 766-767. PubMed
Kirsch A, Werner U, Heinze D: Proteinase inhibiting agents and glucagon in acute pancreatitis. Zentralbl Chir. 1978, 103: 291-303. PubMed
Soergel KH: Medical treatment of acute pancreatitis: what is the evidence?. Gastroenterology. 1978, 74: 620-628. PubMed
Morbidity of acute pancreatitis: the effect of aprotinin and glucagon. Gut. 1980, 21: 334-339.
Freise J, Melzer P, Schmidt FW, Horbach L: Gabexate mesilate in the treatment of acute pancreatitis. Results of a Hannover multicenter double-blind study with 50 patients. Z Gastroenterol. 1986, 24: 200-211. PubMed
Goebell H: Multicenter double-blind study of gabexate mesilate (Foy) given intravenously in low dose in acute pancreatitis [Abstract]. Digestion. 1988, 40: 83-
Harada H, Miyake H, Ochi K, Tanaka J, Kimura I: Clinical trial with a protease inhibitor gabexate mesilate in acute pancreatitis. Int J Pancreatol. 1991, 9: 75-79. PubMed
Cicardi M, Testoni P, Bergamaschini L, Guzzoni S, Cugno M, Buizza M, Bagnolo F: Antiproteasic activity of C1 inhibitor. Therapeutic perspectives. Ann Ital Med Int. 1994, 9: 180-182. PubMed
Chen HM, Chen JC, Hwang TL, Jan YY, Chen MF: Prospective and randomized study of gabexate mesilate for the treatment of severe acute pancreatitis with organ dysfunction. Hepatogastroenterology. 2000, 47: 1147-1150. PubMed
Plint AC, Moher D, Morrison A, Schulz K, Altman DG, Hill C, Gaboury I: Does the CONSORT checklist improve the quality of reports of randomized controlled trials? A systematic review. Med J Aust. 2006, 185: 263-267. PubMed
Uetani K, Nakayama T, Ikai H, Yonemoto N, Moher D: Quality of reports on randomized controlled trials conducted in Japan: evaluation of adherence to the CONSORT statement. Inter Med. 2009, 48: 307-313. 10.2169/internalmedicine.48.1358. CrossRef
Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC: Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974, 139: 69-81. PubMed
- Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II