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泮托拉唑治疗有胃肠出血风险的ICU患者
Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU


Mette Krag ... 其他 • 2018.12.06

泮托拉唑未降低ICU内有胃肠出血风险患者的90死亡率

 

赵言玮*†,赵洁‡,杨军†

†上海嘉会国际医院住院部;‡上海嘉会国际医院重症监护室

*通讯作者

 

在ICU成人患者中预防性使用质子泵抑制剂,例如泮托拉唑,对患者是否有益,是近年来ICU领域的一个热点话题。评估该问题的SUP-ICU(重症监护病房应激性溃疡预防)临床试验结果近日发表于《新英格兰医学杂志》(NEJM1

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摘要


背景

常对重症监护病房(ICU)患者采取措施预防胃肠道应激性溃疡,但其风险和获益尚不清楚。

 

方法

在欧洲这项多中心、平行组、盲法试验中,我们将因急性病被收入ICU(即被收入ICU属于非计划),并且有胃肠出血风险的患者随机分组,在ICU住院期间,接受每日40 mg泮托拉唑(质子泵抑制剂)或安慰剂静脉给药治疗。主要结局为截至随机分组后90日时的死亡。

 

结果

本研究总共纳入3,298例患者;1,645例被随机分配至泮托拉唑组,1,653例被随机分配至安慰剂组。研究获得了3,282例患者(99.5%)的主要结局数据。90日时,泮托拉唑组510例患者(31.1%)和安慰剂组499例患者(30.4%)死亡(相对危险度,1.02;95%置信区间[CI],0.91~1.13;P=0.76)。在ICU住院期间,泮托拉唑组21.9%的患者和安慰剂组22.6%的患者发生了至少1起临床重要的事件(由临床重要的胃肠出血、肺炎、艰难梭菌感染或心肌缺血构成的复合事件;相对危险度,0.96;95% CI,0.83~1.11)。在泮托拉唑组和安慰剂组中,临床重要的胃肠出血发生率分别为2.5%和4.2%。两组90日内出现感染或严重不良反应的患者数量,以及无生命支持情况下的生存天数百分比相似。

 

结论

在有胃肠出血风险的ICU成人患者中,泮托拉唑组患者和安慰剂组患者90日的死亡率和发生的临床重要事件数量相似(由丹麦创新基金[Innovation Fund Denmark]等资助;SUP-ICU在ClinicalTrials.gov注册号为NCT02467621)。





作者信息

Mette Krag, M.D., Ph.D., Søren Marker, M.D., Anders Perner, M.D., Ph.D., Jørn Wetterslev, M.D., Ph.D., Matt P. Wise, M.D., Ph.D., Joerg C. Schefold, M.D., Frederik Keus, M.D., Ph.D., Anne B. Guttormsen, M.D., Ph.D., Stepani Bendel, M.D., Ph.D., Mark Borthwick, M.Sc., Theis Lange, Ph.D., Bodil S. Rasmussen, M.D., Ph.D., Martin Siegemund, M.D., Helle Bundgaard, M.D., Ph.D., Thomas Elkmann, M.D., D.M.Sc., Jacob V. Jensen, M.D., Rune D. Nielsen, M.D., Lisbeth Liboriussen, M.D., Morten H. Bestle, M.D., Ph.D., Jeanie M. Elkjær, M.D., Dorte F. Palmqvist, M.D., Minna Bäcklund, M.D., Ph.D., Jon H. Laake, M.D., Ph.D., Per M. Bådstøløkken, M.D., Juha Grönlund, M.D., Ph.D., Olena Breum, M.D., Akil Walli, M.D., Robert Winding, M.D., Susanne Iversen, M.D., Inge-Lise Jarnvig, M.D., Jonathan O. White, M.D., Björn Brand, M.D., Martin B. Madsen, M.D., Lars Quist, M.D., Klaus J. Thornberg, M.D., Anders Møller, M.D., Jørgen Wiis, M.D., Anders Granholm, B.M.Sc., Carl T. Anthon, M.D., Tine S. Meyhoff, M.D., Peter B. Hjortrup, M.D., Ph.D., Søren R. Aagaard, M.D., Jo B. Andreasen, M.D., Ph.D., Christina A. Sørensen, M.D., Pernille Haure, M.D., Jacob Hauge, M.D., Alexa Hollinger, M.D., Jonas Scheuzger, M.D., Daniel Tuchscherer, M.D., Thierry Vuilliomenet, M.D., Jukka Takala, M.D., Ph.D., Stephan M. Jakob, M.D., Ph.D., Marianne L. Vang, M.D., Kim B. Pælestik, M.D., Karen L.D. Andersen, M.D., Iwan C.C. van der Horst, M.D., Ph.D., Willem Dieperink, Ph.D., Jesper Fjølner, M.D., Cilia K.W. Kjer, B.M.Sc., Christine Sølling, M.D., Ph.D., Christoffer G. Sølling, M.D., Ph.D., Johanna Karttunen, M.D., Matt P.G. Morgan, M.D., Ph.D., Brit Sjøbø, R.N., Janus Engstrøm, B.Sc., Birgit Agerholm-Larsen, Ph.D., and Morten H. Møller, M.D., Ph.D. for the SUP-ICU trial group*
From the Department of Intensive Care (M.K., S.M., A.P., I.-L.J., J.O.W., B.B., M.B.M., L.Q., K.J.T., A.M., J. Wiis, A.G., C.T.A., T.S.M, P.B.H., M.H.M.), Copenhagen Trial Unit, Center for Clinical Intervention Research (J. Wetterslev, J.E.), and the Department of Neurointensive Care (R.D.N, C.S.), Rigshospitalet, Bispebjerg and Frederiksberg Hospital (D.F.P.), and the Section of Biostatistics (T.L.), University of Copenhagen, Copenhagen, Center for Research in Intensive Care (M.K., S.M., A.P., J. Wetterslev, B.S.R., T.L., B.A.-L., M.H.M.), Aalborg University Hospital, Aalborg University, Aalborg (B.S.R., S.R.A., J.B.A., C.A.S., P.H., J. Hauge), Randers Hospital, Randers (H.B., M.L.V., K.B.P., K.L.D.A.), Aarhus University Hospital, Nørrebrogade (T.E., J.F.), and Aarhus University Hospital, Skejby (O.B.) — both in Aarhus, Zealand University Hospital, Køge (J.V.J., C.K.W.K.), Viborg Hospital, Viborg (L.L., C.G.S.), Nordsjællands Hospital, University of Copenhagen, Hillerød (M.H.B.), Holbæk Hospital, Holbæk (J.M.E.), Zealand University Hospital, Roskilde (A.W.), Herning Hospital, Herning (R.W.), and Slagelse Hospital, Slagelse (S.I.) — all in Denmark; the Center for Statistical Science, Peking University, Beijing (T.L.); University Hospital of Wales, Cardiff (M.P.W., M.P.G.M.), and Oxford University Hospitals NHS Foundation Trust, Oxford (M. Borthwick) — both in the United Kingdom; Inselspital, Bern University Hospital, University of Bern, Bern (J.C.S., J.T., S.M.J.), and Basel University Hospital, Basel (M.S., A.H., J.S., D.T., T.V.) — both in Switzerland; University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (F.K., I.C.C.H., W.D.); Haukeland University Hospital, University of Bergen, Bergen (A.B.G., B.S.), and Oslo University Hospital (J.H.L.) and Akershus University Hospital (P.M.B.), Oslo — all in Norway; and Kuopio University Hospital, Kuopio (S.B., J.K.), Helsinki University Hospital, Helsinki (M. Bäcklund), and Turku University Hospital, Turku (J.G.) — all in Finland. Address reprint requests to Dr. Perner at the Department of Intensive Care, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark, or at anders.perner@regionh.dk. *A list of the members of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial group is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Cook DJ, Griffith LE, Walter SD, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care 2001;5:368-375.

2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43:304-377.

3. Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Crit Care Med 1999;27:2812-2817.

4. Krag M, Perner A, Wetterslev J, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med 2015;41:833-845.

5. Barletta JF. Histamine-2-receptor antagonist administration and gastrointestinal bleeding when used for stress ulcer prophylaxis in patients with severe sepsis or septic shock. Ann Pharmacother 2014;48:1276-1281.

6. Krag M, Perner A, Wetterslev J, et al. Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries. Acta Anaesthesiol Scand 2015;59:576-585.

7. Barletta JF, Lat I, Micek ST, Cohen H, Olsen KM, Haas CE. Off-label use of gastrointestinal medications in the intensive care unit. J Intensive Care Med 2015;30:217-225.

8. Krag M, Perner A, Wetterslev J, Wise MP, Hylander Møller M. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med 2014;40:11-22.

9. Cook D, Guyatt G. Prophylaxis against upper gastrointestinal bleeding in hospitalized patients. N Engl J Med 2018;378:2506-2516.

10. MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 2014;174:564-574.

11. Charlot M, Ahlehoff O, Norgaard ML, et al. Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study. Ann Intern Med 2010;153:378-386.

12. Krag M, Perner A, Møller MH. Stress ulcer prophylaxis in the intensive care unit. Curr Opin Crit Care 2016;22:186-190.

13. Krag M, Perner A, Wetterslev J, et al. Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial. Trials 2016;17:205-205.

14. Krag M, Perner A, Wetterslev J, et al. Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan. Acta Anaesthesiol Scand 2017;61:859-868.

15. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309-332.

16. International conference on harmonisation: guidance on statistical principles for clinical trials: availability — FDA. Notice. Fed Regist 1998;63(179):49583-49598.

17. Fergusson D, Aaron SD, Guyatt G, Hébert P. Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ 2002;325:652-654.

18. Kahan BC, Morris TP. Improper analysis of trials randomised using stratified blocks or minimisation. Stat Med 2012;31:328-340.

19. Le Gall J-R, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993;270:2957-2963.

20. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 1996;22:707-710.

21. Jakobsen J, Tamborrino M, Winkel P, et al. Count data analysis in randomised clinical trials. J Biom Biostat 2015;6:227-227.

22. Alhazzani W, Alshamsi F, Belley-Cote E, et al. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med 2018;44:1-11.

23. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 2018;378:797-808.

24. Ridgeon EE, Bellomo R, Aberegg SK, et al. Effect sizes in ongoing randomized controlled critical care trials. Crit Care 2017;21:132-132.

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