提示: 手机请竖屏浏览!

肾上腺素治疗院外心脏停搏的随机试验
A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest


Gavin D. Perkins ... 心脑血管疾病 • 2018.08.23
相关阅读
• 日本的公用除颤设备和院外心脏停搏关系的研究 • 旁观者实施的心肺复苏术和除颤与患者更好的远期结局相关 • 院外心脏停搏后旁观者施救与患者的1年结局研究

摘要


背景

由于对使用肾上腺素治疗院外心脏停搏心存顾虑,因此国际复苏联络委员会(International Liaison Committee on Resuscitation)要求进行安慰剂对照试验,以确定使用肾上腺素治疗这类患者是否安全有效。

 

方法

在英国进行的一项随机、双盲试验纳入了8,014例院外心脏停搏患者,五家国民保健服务(National Health Service)急救中心的急救医士给予患者肠外肾上腺素(4,015例患者)或盐水安慰剂(3,999例患者),并联合标准治疗。主要结局为30日时的生存率。次要结局包括至出院时有良好神经系统结局的生存率,良好神经系统结局的定义为改良Rankin量表(评分范围为0[无症状]~6分[死亡])评分≤3分。

 

结果

30日时,肾上腺素组130例患者(3.2%)和安慰剂组94例患者(2.4%)生存(未校正的生存的比值比,1.39;95%置信区间[CI],1.06~1.82;P=0.02)。在至出院时有良好神经系统结局的生存患者比例方面,无证据表明两组有显著差异(4,007例患者中的87例[2.2%] vs. 3,994例患者中的74例[1.9%];未校正的比值比,1.18;95% CI,0.86~1.61)。出院时,肾上腺素组发生重度神经功能损害(改良Rankin量表评分为4分或5分)的生存者比安慰剂组多(126例患者中的39例[31.0%] vs. 90例患者中的16例[17.8%])。

 

结论

在院外心脏停搏的成人中,肾上腺素组的30日生存率显著高于安慰剂组,但由于肾上腺素组中较多的生存者有重度神经功能损害,因此良好神经系统结局的发生率无显著组间差异(由英国国家健康研究所[U.K. National Institute for Health Research]等资助;在英国随机对照试验注册库注册号为ISRCTN73485024)。 





作者信息

Gavin D. Perkins, M.D., Chen Ji, Ph.D., Charles D. Deakin, M.D., Tom Quinn, M.Phil., Jerry P. Nolan, M.B., Ch.B., Charlotte Scomparin, M.Sc., Scott Regan, B.A., John Long, Anne Slowther, Ph.D., Helen Pocock, M.Sc., John J.M. Black, M.B., B.S., Fionna Moore, M.B., B.S., Rachael T. Fothergill, Ph.D., Nigel Rees, M.Sc., Lyndsey O’Shea, B.Sc., Mark Docherty, M.Sc., Imogen Gunson, M.Sc., Kyee Han, M.B., B.S., Karl Charlton, B.Sc., Judith Finn, Ph.D., Stavros Petrou, Ph.D., Nigel Stallard, Ph.D., Simon Gates, Ph.D., and Ranjit Lall, Ph.D. for the PARAMEDIC2 Collaborators*
From the Warwick Clinical Trials Unit (G.D.P., C.J., C.S., S.R., J.L., S.P., S.G., R.L.) and Warwick Medical School (A.S., N.S.), University of Warwick, Coventry, University Hospitals Birmingham (G.D.P.) and the Cancer Research U.K. Clinical Trials Unit, University of Birmingham (S.G.), Birmingham, South Central Ambulance Service NHS Foundation Trust, Otterbourne (C.D.D., H.P., J.J.M.B.), Southampton Respiratory Biomedical Research Unit, National Institute for Health Research, Southampton (C.D.D.), Kingston University and St. George’s, University of London (T.Q.), and the London Ambulance Service NHS Trust, (F.M., R.T.F.), London, Bristol Medical School, University of Bristol, Bristol, and Royal United Hospital, Bath (J.P.N.), Oxford University Hospitals NHS Foundation Trust, Oxford (J.J.M.B), South East Coast Ambulance Service, Crawley (F.M.), Welsh Ambulance Services NHS Trust, Swansea (N.R., L.O.), West Midlands Ambulance Service NHS Foundation Trust, Brierley Hill (M.D., I.G.), and North East Ambulance Service NHS Foundation Trust, Newcastle Upon Tyne (K.H., K.C.) — all in the United Kingdom; and Curtin University, Perth, WA (J.F.), and Monash University, Melbourne, VIC (J.F.) — both in Australia. Address reprint requests to Dr. Perkins at Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom, or at paramedictrial@warwick.ac.uk. *A complete list of collaborators in the PARAMEDIC2 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics — 2018 update: a report from the American Heart Association. Circulation 2018;137(12):e67-e492.

2. Gräsner JT, Lefering R, Koster RW, et al. Corrigendum to “EuReCa ONE — 27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe” [Resuscitation 105 (2016) 188-195]. Resuscitation 2016;109:145-146.

3. Perkins GD, Travers AH, Berg RA, et al. Adult basic life support and automated external defibrillation: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation 2015;95:e43-e69.

4. Soar J, Callaway CW, Aibiki M, et al. Advanced life support: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation 2015;95:e71-e120.

5. Perkins GD, Cottrell P, Gates S. Is adrenaline safe and effective as a treatment for out of hospital cardiac arrest? BMJ 2014;348:g2435-g2435.

6. Callaway CW. Epinephrine for cardiac arrest. Curr Opin Cardiol 2013;28:36-42.

7. Larsson PT, Wallén NH, Egberg N, Hjemdahl P. Alpha-adrenoceptor blockade by phentolamine inhibits adrenaline-induced platelet activation in vivo without affecting resting measurements. Clin Sci (Lond) 1992;82:369-376.

8. Ristagno G, Tang W, Huang L, et al. Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation. Crit Care Med 2009;37:1408-1415.

9. Lin S, Callaway CW, Shah PS, et al. Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation 2014;85:732-740.

10. Loomba RS, Nijhawan K, Aggarwal S, Arora RR. Increased return of spontaneous circulation at the expense of neurologic outcomes: is prehospital epinephrine for out-of-hospital cardiac arrest really worth it? J Crit Care 2015;30:1376-1381.

11. Kleinman ME, Perkins GD, Bhanji F, et al. ILCOR scientific knowledge gaps and clinical research priorities for cardiopulmonary resuscitation and emergency cardiovascular care: a consensus statement. Resuscitation 2018;127:132-146.

12. Perkins GD, Quinn T, Deakin CD, et al. Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest (PARAMEDIC-2): trial protocol. Resuscitation 2016;108:75-81.

13. Monsieurs KG, Nolan JP, Bossaert LL, et al. European Resuscitation Council guidelines for resuscitation 2015. 1. Executive summary. Resuscitation 2015;95:1-80.

14. Perkins GD, Jacobs IG, Nadkarni VM, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein Resuscitation Registry templates for out-of-hospital cardiac arrest. Resuscitation 2014;96:328-340.

15. Nolan JP, Soar J, Cariou A, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines for post-resuscitation care 2015: section 5 of the European Resuscitation Council guidelines for resuscitation 2015. Resuscitation 2015;95:202-222.

16. Haywood K, Whitehead L, Nadkarni VM, et al. COSCA (Core Outcome Set for Cardiac Arrest) in adults: an advisory statement from the International Liaison Committee on Resuscitation. Resuscitation 2018;127:147-163.

17. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. 6. Advanced cardiovascular life support: section 6: pharmacology II: agents to optimize cardiac output and blood pressure. Circulation 2000;102:Suppl:I-129–I-135.

18. Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL. Effect of adrenaline on survival in out-of-hospital cardiac arrest: a randomised double-blind placebo-controlled trial. Resuscitation 2011;82:1138-1143.

19. Ong MEH, Perkins GD, Cariou A. Out-of-hospital cardiac arrest: prehospital management. Lancet 2018;391:980-988.

20. Berdowski J, Beekhuis F, Zwinderman AH, Tijssen JG, Koster RW. Importance of the first link: description and recognition of an out-of-hospital cardiac arrest in an emergency call. Circulation 2009;119:2096-2102.

21. Hasselqvist-Ax I, Riva G, Herlitz J, et al. Early cardiopulmonary resuscitation in out-of-hospital cardiac arrest. N Engl J Med 2015;372:2307-2315.

22. Kitamura T, Kiyohara K, Sakai T, et al. Public-access defibrillation and out-of-hospital cardiac arrest in Japan. N Engl J Med 2016;375:1649-1659.

23. Deakin CD, Yang J, Nguyen R, et al. Effects of epinephrine on cerebral oxygenation during cardiopulmonary resuscitation: a prospective cohort study. Resuscitation 2016;109:138-144.

24. Casas AI, Geuss E, Kleikers PWM, et al. NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage. Proc Natl Acad Sci U S A 2017;114:12315-12320.

25. Busl KM, Greer DM. Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms. NeuroRehabilitation 2010;26:5-13.

26. Hoke RS, Chamberlain D. Skeletal chest injuries secondary to cardiopulmonary resuscitation. Resuscitation 2004;63:327-338.

27. Nolan JP, Ferrando P, Soar J, et al. Increasing survival after admission to UK critical care units following cardiopulmonary resuscitation. Crit Care 2016;20:219-219.

28. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med 2004;30:2126-2128.

29. Nichol G, Brown SP, Perkins GD, et al. What change in outcomes after cardiac arrest is necessary to change practice? Results of an international survey. Resuscitation 2016;107:115-120.

30. Morrison LJ, Visentin LM, Kiss A, et al. Validation of a rule for termination of resuscitation in out-of-hospital cardiac arrest. N Engl J Med 2006;355:478-487.

31. Fried TR, Bradley EH, Towle VR. Assessment of patient preferences: integrating treatments and outcomes. J Gerontol B Psychol Sci Soc Sci 2002;57:S348-S354.

32. Hanger HC, Fogarty B, Wilkinson TJ, Sainsbury R. Stroke patients’ views on stroke outcomes: death versus disability. Clin Rehabil 2000;14:417-424.

33. Angelos MG, Butke RL, Panchal AR, et al. Cardiovascular response to epinephrine varies with increasing duration of cardiac arrest. Resuscitation 2008;77:101-110.

34. Kudenchuk PJ. Early epinephrine in out-of-hospital cardiac arrest: is sooner better than none at all? Resuscitation 2013;84:861-862.

35. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016;353:i1577-i1577.

36. Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med 2008;359:21-30.

服务条款 | 隐私政策 | 联系我们