By Greg Gipson 8/30/13

Vasopressin, steroids, and epinephrine and

neurologically favorable survival after in-hospital

cardiac arrestMentzelopoulos, et al.

By Greg Gipson8/30/13

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

The cardiac arrest problem

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

http://www.heart.org/HEARTORG/

http://www.kingcounty.gov/health/ems

AHA 2010 algorithm◦ CPR◦ Shock◦ Drugs

Epi 1mg q3-5min Vasopressin 40 IU

Amio 300mg Repeat 150mg

◦ Return of spontaneous circulation (ROSC)

Standard of care

American Heart Association, http://www.heart.org/HEARTORG/, accessed 8/27/13

http://www.heart.org/HEARTORG/

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

Challenging the Status Quo

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

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

Study Design

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.

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

Protocol


No ROSC by 5th cycle◦ Follow European

resuscitation guidelines

◦ Epi 1mg q3-5min

◦ Option: Amio, atropine, magnesium

Protocol

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

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

Protocol


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

Outcomes

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.

Power calculations◦ N=244

ITT Tested

◦ Normality◦ Heterogeneity

Analysis


Analysis methods◦ Chi2 or Fischer exact◦ T-tests◦ Linear-mixed model◦ Logistic regression◦ Multivariate Cox

Results


Figure 1

Comparable baseline characteristics

Results


Results


MAP higher on days 1, 2, 4, 5, 10 post resuscitation

ScvO2 higher on days 1, 2, 4-10 post resuscitation

Results


More organ failure free days and ventilator free days in treatment group

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

Results


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

Discussion

Papastylianou A, Mentzelopoulos S. Current pharmacological advances in the treatment of cardiac arrest. Emergency Medicine International 2012,815857;9.

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

Discussion

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

http://mcatprep4free.blogspot.com/2011/08/antidiuretic-hormone-adh.html

http://mcatprep4free.blogspot.com/2011/08/antidiuretic-hormone-adh.html

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

Discussion

Patel G, Balk R. Systemic steroids in severe sepsis and septic shock. American Journal of Respiratory and Critical Care Medicine. 2012;2:133-139Skyschally 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

http://images.ddccdn.com/drp/images/12/80007201.jpg

VSE◦ ↑ ROSC◦ ↑ Survival and neurologic outcomes◦ ↑ Hemodynamics◦ ↓ Organ failure◦ ? Corticosteroid complications

↑ Insulin use ↔ Hyperglycemia

Summary

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?

Discussion

Questions

By Greg Gipson 8/30/13

Documents

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