Upload
zinnia
View
58
Download
0
Embed Size (px)
DESCRIPTION
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 - PowerPoint PPT Presentation
Citation preview
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
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