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By Greg Gipson 8/30/13

Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest Mentzelopoulos , et al. By Greg Gipson 8/30/13. The cardiac arrest problem. Out-of-hospital US survival rate 11.4% King County survival rate 52% In-hospital

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By Greg Gipson 8/30/13

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  1. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrestMentzelopoulos, et al. By Greg Gipson 8/30/13

  2. The cardiac arrest problem • Out-of-hospital • US survival rate 11.4% • King County survival rate 52% • In-hospital • Estimated 6.7 per 1000 admissions • 200,000 patients/year • Neurologic damage • Survival to discharge 24.2% • Still room for improvement American Heart Association, http://www.heart.org/HEARTORG/, accessed 8/27/13 EMS 2012 Annual Report, available at www.kingcounty.gov/health/ems, accessed 8/27/13

  3. Standard of care AHA 2010 algorithm • CPR • Shock • Drugs • Epi 1mg q3-5min • Vasopressin 40 IU • Amio 300mg • Repeat 150mg • Return of spontaneous circulation (ROSC) American Heart Association, http://www.heart.org/HEARTORG/, accessed 8/27/13

  4. Challenging the Status Quo Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest • Previous trial showed benefit • RCT, single center, n=100 • ↑ROSC, ↑survival to discharge, similar ADEs • Neurologically survival ≠ survival • Further investigate treatment algorithm • Published: JAMA - July 2013 Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279. Mentzelopoulos S, Zakynthinos S, Tzoufi M, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest

  5. Study Design • RC, DB, PC, parallel-group, MC • Pharmacists randomized • Sept 1, 2008 – Oct 1, 2010 • 3 Greek tertiary care hospitals • N=268 consecutive patients • Exclusion • <18 y/o, terminal illness, DNR, exsanguination, arrest before admission, IV steroids, previous enrollment/exclusion Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  6. Protocol • Cardiac arrest! • Begin CPR (30:2) • Intervention q 3 minutes, x 5 times • Tx: Vasopressin 20 IU and epi 1mg • Control: Saline placebo and epi 1mg • First cycle ONLY • Tx: Methyprednisolone 40mg IV • Control: Saline placebo Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  7. Protocol • No ROSC by 5th cycle • Follow European resuscitation guidelines • Epi 1mg q3-5min • Option: Amio, atropine, magnesium Nolan JP, Deakin CD, Soar J. European resuscitation council. European resuscitation council guidelines for resuscitation 2005: Section 4, Adult advanced life support. Resuscitation. 2005;37(suppl 1):@39-S86

  8. Protocol • 4 hours post resuscitation • Postresuscitation shock? • Tx: Hydrocortisone 300 mg/d CI, ≤ 7 days, then taper • Unless AMI, then ≤ 3 days • Control: Saline infusions • Could receive open-label hydrocortisone Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  9. Outcomes • Primary • ROSC x ≥20 minutes • Survival to discharge w/ CPC 1 or 2 • Secondary • Atrial pressure 20 min post ROSC • Atrial pressure + ScvO2 (days 1-10) • Organ failure free days (days 1-60) • Corticosteroid complications • Hyperglycemia, infection, PUD, paresis Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279. Grenvik A, Safar P. Eds: Brain failure and resuscitation, Churchill Livingstone, New Yortk, 1981; 155-184.

  10. Analysis • Power calculations • N=244 • ITT • Tested • Normality • Heterogeneity • Analysis methods • Chi2 or Fischer exact • T-tests • Linear-mixed model • Logistic regression • Multivariate Cox Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  11. Results • Figure 1 Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  12. Results • Comparable baseline characteristics Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  13. Results Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  14. Results Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  15. Results Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  16. Results Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  17. Results Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  18. Results Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  19. Results • MAP higher on days 1, 2, 4, 5, 10 post resuscitation • ScvO2 higher on days 1, 2, 4-10 post resuscitation Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  20. Results • More organ failure free days and ventilator free days in treatment group Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  21. Results • Adverse events from corticosteroids • Tx group • Used more insulin (p<0.001) • No difference in hyperglycemia (>180mg/dL, p=0.88) • No other ADEs reported Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279.

  22. Discussion • Epinephrine • Adrenergic agonist • Vasoconstriction • ↑Cerebral perfusion • ↑Coronary perfusion • ↑HR, ↑CO • ↑Cerebral perfusion • ↑Coronary perfusion • ↑Myocardial O2 consumption • Effect attenuated in hypoxia and acidosis • T1/2 = 2-3 min • Peak concentration ~90 sec Papastylianou A, Mentzelopoulos S. Current pharmacological advances in the treatment of cardiac arrest. Emergency Medicine International 2012,815857;9.

  23. Discussion • Vasopressin • Vasopressin receptor agonist (V1,2,3) • V1 – Vasoconstriction • ↑ Cerebral perfusion • V2 – Antidiuresis (distal convoluted tubule, medullary collecting duct) • V3 – Insulin, ACTH, temp, BP, memory (anterior pituitary, islet cells) • Survivors show low vasopressin levels • T1/2 = 10-35 min • Data shows: Vasopressin = Epi Papastylianou A, Mentzelopoulos S. Current pharmacological advances in the treatment of cardiac arrest. Emergency Medicine International 2012,815857;9. Image from: MCAT Review, http://mcatprep4free.blogspot.com/2011/08/antidiuretic-hormone-adh.html, Accessed 8/28/13

  24. Discussion • Corticosteroids • Use is controversial • Adrenal dysfunction possible in shock • Not standard of practice for cardiac resuscitation • ↑ effect of epinephrine • ↑ effect of vasopressin • ↑ myocardial function post arrest • Other possibly beneficial effects • Anti-inflammatory • Increase fluid volume • ADEs Patel G, Balk R. Systemic steroids in severe sepsis and septic shock. American Journal of Respiratory and Critical Care Medicine. 2012;2:133-139 Skyschally A, Haude M, Dorge H, et al. Glucocorticoid treatment prevents progressive myocardial dysfunction resulting from experimental coronary microembloism. Circulation 2004;109(19):2337-2342. Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest. JAMA 2013;310(3):270-279. Image from: http://images.ddccdn.com/drp/images/12/80007201.jpg, Accessed 8/28/13

  25. Summary • VSE • ↑ ROSC • ↑ Survival and neurologic outcomes • ↑ Hemodynamics • ↓ Organ failure • ? Corticosteroid complications • ↑ Insulin use • ↔ Hyperglycemia

  26. Discussion • Can we safely apply these results to a US population? • Should we repeat this trial in King County? • What will the next AHA ACLS guidelines recommend? • Will they incorporate this data?

  27. Questions

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