By Greg Gipson
8/30/13
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Out-of-hospital
◦ US survival rate 11.4%
◦ King County survival rate 52%
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In-hospital
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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
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
Vasopressin, steroids, and epinephrine and
neurologically favorable survival after inhospital 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
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RC, DB, PC, parallel-group, MC
◦ Pharmacists randomized
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Sept 1, 2008 – Oct 1, 2010
3 Greek tertiary care hospitals
N=268 consecutive patients
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Exclusion
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◦ <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.
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Cardiac arrest!
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Begin CPR (30:2)
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Intervention q 3 minutes, x 5 times
◦ Tx: Vasopressin 20 IU and epi 1mg
◦ Control: Saline placebo and epi 1mg
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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.
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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
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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.
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Primary
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Secondary
◦ ROSC x ≥20 minutes
◦ Survival to discharge w/ CPC 1 or 2
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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.
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Power calculations
◦ N=244
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ITT
Tested
◦ Normality
◦ Heterogeneity
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Analysis methods
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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.
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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.
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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.
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, 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, 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, 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, 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, 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.
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
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.

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.

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.
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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.
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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
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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
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VSE
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↑ ROSC
↑ Survival and neurologic outcomes
↑ Hemodynamics
↓ Organ failure
? Corticosteroid complications
 ↑ Insulin use
 ↔ Hyperglycemia
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
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?