Revisión del Artículo y la literatura disponible

1. ToxicologyJournal Club Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial Resuscitation. 2011 Sep;82(9):1138-43. Epub 2011 Jul 2. Juan Pablo Peña Diaz, MD Medicina de Urgencias

2. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Effect of adrenaline on survival in out-of-hospital cardiac arrest: Ian G. Jacobs, Judith C. Finn, George A. Jelinek, Harry F. Oxer, Peter L. Thompson

3. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Cardiovascular disease caused the dead of 15 million people in 1996 (29 % global mortality) Ischemic Heart Disease: 7 million/people/year Risk for Sudden Death: 5 to 7 times Incidence in USA: 95.7 per 100,000 person years Becker L, Larsen MP, Eisenberg MS. Incidence of cardiac arrest during self-transport for chest pain. Ann EmergMed. 1996 Dec;28(6):612-6 Nichol G, Thomas E, Callaway CW, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 2008;300:1423–31. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD. Heart Disease and Stroke Statistics 2010 Update: A report from the American Heart Association. Circulation. 2011;123

4. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias AMI: 295.000 people die before hospital arrival (70%) 55% to 60% were attended by EMS Commonest cardiac arrest rhythm: VF / VT (23% a 30%) Survival to hospital discharge: < 7% Becker L, Larsen MP, Eisenberg MS. Incidence of cardiac arrest during self-transport for chest pain. Ann EmergMed. 1996 Dec;28(6):612-6.

5. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias OnlyClass I Evidence Closed-chest cardiacmassage. JAMA. 1960 Jul 9;173:1064-7.

6. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Routine use of adrenaline (epinephrine) in treating cardiac arrest has been recommended for over half a century Firstdescribed in 1906:

7. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias JAMA. 1968 Jan 22;203(4):255-60.

8. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Ann Emerg Med September 1984 (Part 2);13:840-843

9. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Weconcludethatepinephrineproduces a significantdose-dependent vasopressor responseduring CPR in humanbeings. Thisfindingsupports work in animal modelsandanecdotalreports in humanbeings, indicatingthat doses ofepinephrinethat are higherthanthosecurrentlyrecommendedmaybeneededduring late CPR in humanbeings. AnnEmergMed , September 1989;18:920-926

10. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Resus, 1.995 EMS setting Observational Prospective 417: Adrenaline 786: No Adrenaline AuthorizedbyMedicaldispatcher

12. 681 epinephrine phaseAIM: Evaluatethe incremental benefit of introducing intravenous epinephrine in the out-of-hospital setting on the survival outcomes of cardiac arrest patients

13. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias There was no significant difference in survival to discharge, adjusted for rhythm; return of circulation or survival to admission There was a minimal increase in scene time in the epinephrine phase (10.3 minutes versus 10.7 minutes) Conclusion: We were unable to establish a significant survival benefit with the introduction of IV epinephrine to an EMS system

14. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Objective: To determine whether removing intravenous drug administration from an ACLS protocol would improve survival to hospital discharge after out-of-hospital cardiacarrest. Prospective Randomized Controlled Non Blinded JAMA. 2009;302(20):2222-2229

16. 433 were in the ACLS with no access to IV drug administration group- Survivalto hospital discharge was 10.5% for the IV vs 9.2% for the no IV drug administration group (P=.61) - Hospital admission with ROSC 32% vs 21%, (P.001) - Survival with favorable neurological outcome 9.8% vs 8.1% (P=.45) - Survival at 1 year 10% vs8%(P=.53)

17. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Despite adrenaline being universally considered “standard of care” in the treatment of cardiac arrest there has never been a randomized placebo-controlled trial to establish its efficacy.

18. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Methods

19. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Study patients and setting:

20. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias

21. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Perth

22. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias All calls for ambulances throughout WA are received centrally and ambulances dispatched by the ambulance service communication centre located in Perth. All ambulances in Perth and larger regional centres in WA are staffed by career PMDs where their scope of clinical care is governed by specific SJA-WA clinical practice guidelines.

23. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias The management of cardiac arrest is based on the recommendations of the Australian Resuscitation Council - Defibrillationwith a manual Defibrillator - Securing the airway (TT or LMA)- No drugs were administered

25. Placebo (sodiumchloride 0.9%)Out-of-hospital cardiac arrest patients attended by SJA-WA EMS

27. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias The study was approved by the of the and waiver (disclaim) of consent was granted

29. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Afterarrivalto hospital, treatingED clinicians were unaware of drug assignment and managed the patient as per their usual clinical practice (Guidelines) Data collection Manually recorded by the paramedic Clinically reviewed and data manually entered into the SPSS statisticalpackage These form the WA Ambulance Service Cardiac Arrest Registry CPC scores are derived from medical chart, the reviewer was blinded to the study group allocation

30. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Statisticalanalysis The sample size required for the study was 2213 patients per group This was derived on a baseline survival to hospital discharge of 5% with an absolute improvement in survival of 2%, alpha 0.05 (two tailed) and power of 80% A total patient enrollment of 5.000 was planned to account for losses to follow-up.

31. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Patient and study characteristics were described using proportions and means, with differences assessed using Pearson’s chi-square and t-test (or Mann–Whitney) for categorical and continuous data respectively Ambulance time intervals were described using means, medians and interquartile ranges (IQR). Odds ratios (OR) and 95% confidence intervals were derived for primary and secondaryoutcomes.

32. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Logistic regression was used to adjust for potential confounders on the treatment effect of the study Drug It was planned ‘a priori’ to conduct subgroup analysis of primary and secondary outcomes by shockable versus non-shockable initial cardiac arrest rhythm Analysis was performed on an intention to treat basis and per protocol basis using SPSS statistical software version 17 All statistical tests were two sided with a significancelevel of 0.05.

33. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Studyprofile

34. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias

35. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Patients administered adrenaline the likelihood of achieving ROSC pre-hospital was 3.4 times greater than for those receiving placebo (23.5% versus 8.4%; OR 3.4; 95% CI 2.0–5.6)

36. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Adrenaline was associated with a significant increase in the proportion of patients admitted from the ED to hospital (25.4% versus 13.0%; OR 2.3; 95% CI 1.4–3.6).

37. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias More thantwicethenumber of patients who received adrenaline survived to hospital discharge, but this failed to reach statistical significance (4.0% versus 1.9%; OR 2.2; 95% CI 0.7–6.3)

38. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Good neurological outcome (CPC 1 or 2) was achieved in 14 out of the 16 survivors. The two unfavourable neurological outcomes (one CPC = 3 and one CPC = 4) occurred in theadrenalinegroup.

39. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Treatment effect of adrenaline on prehospital ROSC was more marked in non-shockable rhythms (OR 6.9; 95% CI 2.6–18.4) than shockable rhythms (OR 2.4; 95% CI 1.2–4.5)

40. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Adjusted models Little change in the effect of adrenaline on ROSC or survival to hospital discharge The presence of an initial shockable rhythm was the only other factor associated with the likelihood of pre-hospital ROSC A younger age and an initial shockable rhythm was also associated with improved survival to hospital discharge

42. For both shockable and non-shockable initial cardiacarrest rhythms we observed significantly better outcomes interms of ROSC and hospital admission with the use of adrenaline.

43. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Whatthisstudydemonstrates is that the administration of resuscitation drugs during out of hospital cardiac arrest is associated with improvements in short termsurvival. Thisstudy“clearlydemonstrates the superiority of adrenaline over placebo in achieving ROSC” All the studies published to date have employed less robust study designs, used adrenaline doses much lower than recommended for cardiac arrest or compared larger doses of adrenaline againstunprovenstandarddoseadrenalineregimes.

44. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Thisisanout-of-hospital study, theinfluence of post resuscitation care interventions (therapeutic hypothermia, managing underlying cause, organ perfusion and oxygenation) on survival to hospital discharge are recognised

45. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Limitations Failure to achieve an adequatesample size Despite having obtained approvals for the study, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating Adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns.

46. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Theextensivebarriersassociated with trialling interventions deemed “standard of care” where clinical equipoise clearly exists serves only to ensure such interventions remain unproven The findings of this study are clinically important in that it establishes efficacy for the continued use of adrenaline in cardiac arrest as currently recommended, however numerous questions remain unanswered …

47. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias What is the optimal dose ? When is the moment for adrenaline during cardiacarrest ?

48. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Robert R Attaran & Gordon A Ewy Future Cardiology. July 2010, Vol. 6, No. 4, Pages 473-482 Vasopressor drugs will be more effective with wider adoption of strategies that delay the inevitable deterioration that accompanies untreated or suboptimally treated cardiac arrest.

49. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias Cardiac arrest survival rates are mutable Michael R. Sayre Resuscitation 82 (2011) 1257– 1258 Measurement of survival to hospital discharge following out of-hospital cardiac arrest should be expected of all EMS systems. EMS systems should publicly report their hospital discharge survival rates to their political leaders and the citizens they serve as well as the EMS professionals and hospital staffs caring for those patients.

50. Effect of adrenaline on survival in out-of-hospital cardiac arrest ToxicologyJournal Club Juan Pablo Peña Diaz, MD / Medicina de Urgencias ThankYou !