by greg gipson 8/30/13. out-of-hospital ◦ us survival rate 11.4% ◦ king county survival rate...

Vasopressin, steroids, and epinephrine and

neurologically favorable survival after in-hospital

cardiac arrest

Mentzelopoulos, 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

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

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

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.

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

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.

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

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.

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

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.

Figure 1

Comparable baseline characteristics

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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

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.

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

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.

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

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

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