ROSC!
Now what??!!
An EMS Guide to the Management of
Post Cardiac Arrest Syndrome
Jay Lance Kovar, MD, FACEP
Montgomery County Hospital District
PHI Air Medical Texas
Objectives
o Review
o Background and Epidemiology of Cardiac Arrest Survival
o Detail
o Pathophysiology of Post Cardiac Arrest Syndrome
o Discuss
o Monitoring, Therapeutic Strategies, and Protocols they apply to the
Pre-Hospital Environment
o Propose
o Integrated EMS Protocols for Improved Intact Neurologic
Survivability
Background
o 1966
Nat'l Academy Sciences Nat'l Research Council on
CPR
describes ABCD’s
o 1972
Dr Valdimir Negovsky “The Second Step”
o Advances in CPR and cardiac care has not resulted in improved
survivability in 50 years
o Post Cardiac Arrest Syndrome
o Brain Injury
o Myocardial Dysfunction
o Systemic Ischemia/Reperfusion Response
o Unresolved Pathological Process
Background
o Barriers to Optimal Outcomes
oMultiple Teams/Hand-0ffs
oWide variation in Treatments (multicenter trials)
oEarly Prognostication Inaccuracies < 72 hrs
oResearch focus on ROSC
oImproved ROSC
w/o Improved Survival
Epidemiology
o Early Mortality rates after ROSC varies greatly between
studies, regions, and hospitals indicating variability in Post
Cardiac Arrest Care
o Advances in Critical Care over past 5 decades fails to produce
improved outcomes
o Data Definition Confusion
o ROSC
o Mortality Location
o OOH/IH
o Mortality Time
Epidemiology
o Physiologic Phases of Post Cardiac Arrest Care
o Immediate = 0-20 minutes
o CPR interventions
o Early = 20 minutes – 6 to 12 hours
o Early interventions most effective
o Intermediate = 6 to 12 hours – 72 hours
o Aggressive management of Injury pathways
o Recovery = beyond 3 days
o Prognostication Reliable
o Outcomes Predictable
Epidemiology
o Mortality Rates Inadequate
o Neurologic and Functional
Outcomes
o Cerebral Performance Category
Epidemiology
Quality of Life?
o Limitation and Withdrawal of Therapy
o 63% made DNR, 43% withdrew Therapy in Early and
Intermediate time periods << Prognostic period
o Can better Care w/i 72 hours result in improved Survivability
or increased Organ Donation and Quality?
Pathophysiology
o Unique Process involving Multiple Organ Systems
o Ischemic Injury
o Additional Damage During and After Reperfusion
o Additive to PreArrest Pathology
o Post Cardiac Arrest brain Injury
o Post Cardiac Arrest Myocardial Dysfunction
o Systemic Ischemia/Reperfusion Response
o Persistent Precipitating Pathology (P5)
Brain Injury
o 68% OOH Mortality 23% IH Mortality
o Limited Tolerance of Ischemia
o Unique Reperfusion Response post ROSC lasting Hours to
Days
o Excitotoxicity
o Disrupted Ca++ Homeostasis
o Free Radical Formation
o Pathologic Protease Cascades
o Activation of Cell Death Pathways
Brain Injury
o Protracted Injury Phase opens Broad Therapeutic Window
o Cerebral Perfusion becomes dependent upon CePP not
Autoregulation or Neuronal Activity
o Migratory Intravascular Thrombosis with CPR > 15 minutes (No
Reflow)
o Hyperemic Flow increases Edema
o Luxuriant Hyperperfusion
o Excessive Oxygen Free radical Formation
Brain Injury
o Global CBF is reduced but adequate to meet Oxidative Metabolic
Demands in first 48 hours
o Transient Edema common post Arrest but rarely increases ICP
o Delayed Edema attributable to Ischemic Neurodegradation
o Pyrexia
o – Poor Outcome Increases with each degree > 370C
o Hyperglycemia
o – Common and Potentially Mitigated with Insulin Rx
o Seizures
o – Associated with Worst Prognosis
o -- Caused by and Exacerbates Injury
Myocardial Dysfunction
o Responsive to Therapy and Reversible
o Detectible within minutes of ROSC
o Decreased EF (stunned)
o Increased LVEDP (stiff)
o Coronary Blood Flow Normal = Myocardial Stunning
o Nadir @ 8 Hrs, Improve @ 24 Hrs, Normal @ 72+ Hrs
o Dobutamine improves LVEF and Diastolic Dysfunction
Systemic Response
o CPR generates poor Cardiac Output, O2 delivery ,and
MetaboliteClearance
o Oxygen Debt leads to Endothelial Activation and Systemic
Inflammation
o Predictive of MOSF and Death
o Common Sepsis Features
o Adrenal Insufficiency
o Responsive to Therapy and Reversible
o Early Goal Directed Therapy may Optimize Outcomes
Persistent Pathology
o Precipitating or Contributory Pathology
o ACS
o AMI >50% OOH Adult Arrests
o 48% Acute Coronary Occlusion w/o apparent STEMI
o Biomarker Specificity Reduced yet 96% Sensitive for AMI
Persistent Pathology
o Precipitating or Contributory Pathology
o Pulmonary Embolism
o Up to 10% Incidence in Sudden Death
o Unknown ROSC Rate
o COPD, Asthma, or Pneumonia
o Pulmonary Function often Worsens post ROSC
o Brain Injury and Edema more common after Asphyxic Arrest
o Sepsis
o Infections more common cause of In Hospital Arrests
o Toxins
o Environmental
Therapeutic Strategy
o Critical Care Standards for EMS and ED
o Time Sensitive
o Account for In/Out of Hospital Settings
o Sequential care by multiple Diverse Teams
o Accommodate Spectrum of patients
o Awake, Stable to Unstable Comatose
October 2007
Out-of-Hospital Cardiac Arrest Survival after the Sequential Implementation
of 2005 AHA Guidelines for Compressions, Ventilations, and Induced
Hypothermia
J. Brent Myers, MD MPH Medical Director Wake County EMS System
11.6%
16
14
12
10
8
6
8.2%
P<0.05*
7.3%
4.6%
4
2
0
Baseline
New CPR
* when compared with baseline
ITD
Hypo
I want a new drug
• A study of ventricular fibrillation victims, 75% of the surviving patients
had a return of spontaneous circulation without injection of a
vasopressor; the remaining 25% of patients who required a vasopressor
indicated that, if basic life support does not restore spontaneous
circulation, the general outcome is most probably poor.
Bunch TJ, White RD, Gersh BJ, Meverden RA, Hodge DO, Ballman KV, Hammill SC, Shen WK, Packer DL: Long-term outcomes of out-of-hospital cardiac arrest after successful early
defibrillation.
N Engl J Med 2003, 348:2626-2633.
• Accordingly, once advanced cardiac life support drugs are necessary,
rescuers need to understand that the chance the patient will be
discharged from the hospital is <10%
Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH: A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary
resuscitation.
N Engl J Med 2004, 350:105-113.
Epinephrine
• employed in CPR for 100 years
• dosage "lumps together" of all etiologies despite differencesin
myocardial energetics, postresuscitation function, neurological
lesions, and mortality between ventricular fibrillation and other
etiologies of arrest
• ACLS dose of 1 mg bolus results in dosevariability corresponding
to 10 µg/kg in a 100-kg person but 25 µg/kg in a 40-kg person.
• increases myocardial oxygen consumption during
cardiopulmonary resuscitation
• increases the likelihood of cardiac failure after restoration of
spontaneous circulation via diastolic dysfunction
• "But if you don't have a smashing alternative to the drug, you
often just keep using it."
Vasopressin
• successfully resuscitated cardiac-arrest patients found to have
higher endogenous vasopressin levels than those patients who die
• vasopressin increases blood pressure differently in the body,
constricting the vessels in nonvital organs and dilating the blood
vessels in the brain and in the heart
• vasopressin appears to work best when ischemia is substantial
• typically used only as alternative – and late
• Vasopressin is an orphan drug
• Is marketing of vasopressin essential to the drug being used by
emergency physicians treating cardiac-arrest patients?
Vasopressin versus continuous adrenaline during experimental cardiopulmonary resuscitation
Resuscitation, Volume 62, Issue 1, Pages 61-69 2004
J.Johansson, R.Gedeborg, S.Rubertsson
• Objective:
– To evaluate the effects of a bolus dose of vasopressin compared to continuous adrenaline
(epinephrine) infusion on vital organ blood flow during cardiopulmonary resuscitation (CPR).
• Results:
– Vasopressin generated higher cortical cerebral blood flow (P<0.001) and lower cerebral
oxygen extraction (P<0.001) during CPR compared to continuous adrenaline.
– Coronary perfusion pressure during CPR was higher in vasopressin-treated pigs (P<0.001) and
successful resuscitation was achieved in 12/12 in the vasopressin group versus 5/12 in the
adrenaline group (P=0.005).
• Conclusions:
– In this experimental model, vasopressin caused a greater increase in cortical cerebral blood
flow and lower cerebral oxygen extraction during CPR compared to continuous adrenaline.
Furthermore, vasopressin generated higher coronary perfusion pressure and increased the
likelihood of restoring spontaneous circulation.
Effects of epinephrine and vasopressin on end-tidal carbon dioxide tension and mean arterial blood pressure in
out-of-hospital cardiopulmonary resuscitation: an observational study
Stefan Mally , Alina Jelatancev and Stefek Grmec
Centre for Emergency Medicine Maribor, Ljubljanska 5, 2000 Maribor, Slovenia
Critical Care 2007, 11:R39doi:10.1186/cc5726
• 1 mg of epinephrine intravenously every three minutes only vs vasopressin/epinephrine group
40 units of vasopressin intravenously only or followed by 1 mg of epinephrine every three
minutes during CPR. Values of end-tidal carbon dioxide and MAP were recorded, and data were
collected according to the Utstein style.
• Results
– Final end-tidal carbon dioxide values and average values of MAP in patients with
restoration of pulse were significantly higher in the vasopressin/epinephrine group (p <
0.01). End-tidal carbon dioxide values as well as MAP at admission to the hospital were
associated with survival at 24 hours and improved hospital discharge.
– In the vasopressin group, significantly more pulse restorations and a better rate of survival
at 24 hours were observed (p < 0.05). Subgroup analysis of patients with initial asystole
revealed a higher hospital discharge rate when vasopressin was used (p = 0.04).
– Neurological outcome in discharged patients was better in the vasopressin group (p = 0.04).
• Conclusion
– End-tidal carbon dioxide and MAP are strong prognostic factors for the outcome of out-ofhospital cardiac arrest. This combination vasopressor therapy improves restoration of
spontaneous circulation, short-term survival, and neurological outcome. In the subgroup of
patients with initial asystole, it improves the hospital discharge rate.
A Comparison of Vasopressin and Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation
Volker Wenzel, M.D., Anette C. Krismer, M.D., H. Richard Arntz, M.D., Helmut Sitter, Ph.D., Karl H.
Stadlbauer, M.D., Karl H. Lindner, M.D., for the European Resuscitation Council Vasopressor during
Cardiopulmonary Resuscitation Study Group
• Methods
– 40 IU ofvasopressin vs 1 mg of epinephrine, followed by additional treatment with
epinephrine if needed.
• Results
– A total of 1186 patients.
– Among patients with asystole, however, vasopressin use was associated with
significantly higher rates of hospital admission (29.0 percent, vs. 20.3; P=0.02) and
hospital discharge (4.7 percent vs. 1.5 percent, P=0.04).
– Among patients in whom spontaneous circulation was not restored with the two
injections of the study drug, additional treatment with epinephrine resulted in
significant improvement in the rates of survival to hospital admission and hospital
discharge in the vasopressin group, but not in the epinephrine group (hospital
admission rate, 25.7 percent vs. 16.4 percent; P=0.002;
– hospital discharge rate, 6.2 percentvs. 1.7 percent; P=0.002).
– Cerebral performance was similar in the two groups.
• Conclusions The effects of vasopressin were similar to those of epinephrine in
the management of ventricular fibrillation and pulseless electrical activity, but
vasopressin was superior to epinephrine in patients with asystole. Vasopressin
followed by epinephrine may be more effective than epinephrine alone in the
treatment of refractory cardiac arrest.
Combination vasopressin/epinephrine does not improve cardiac-arrest
outcomes
"The lack of superiority of combination therapy over epinephrine alone, regardless
of the patient subgroup, suggests it may be futile to add vasopressin to
epinephrine during cardiopulmonary resuscitation with advanced cardiac life
support,"
Dr Pierre-Yves Gueugniaud et al,July 3, 2008 New England Journal of Medicine.
• Investigators assigned 1442 adults to 1 mg of epinephrine and 40 IU of
vasopressin and 1452 adults to 1 mg of epinephrine alone, with the
combination of drugs repeated if spontaneous circulation was not restored
within three minutes after the first administration. Patients were subsequently
given additional epinephrine alone if needed.
• The combination therapy with vasopressin and epinephrine did not result in
any significant improvement over epinephrine alone. The rates of survival to
hospital admission, return of spontaneous circulation, survival to hospital
discharge, survival at one year, and neurologic recovery at discharge were
similar in both treatment arms.
• Gueugniaud and colleagues point out that very few patients in their study had
ventricular fibrillation—less than 10% in both treatment arms—and this
"precludes a definitive conclusion against the use of vasopressin."
• Survivorship to hospital discharge average 2% for both groups
Repeat?
Repeated Administration of Vasopressin but Not Epinephrine Maintains Coronary Perfusion
Pressure After Early and Late Administration During Prolonged Cardiopulmonary
Resuscitation in Pigs
Volker Wenzel, MD; Karl H. Lindner, MD; Anette C. Krismer, MD; Egfried A. Miller, BS; Wolfgang G.
Voelckel, MD; Werner Lingnau, MD
Question
Should vasopressin be injected during CPR
based on results from a subgroup analysis
and retrospective studies?
“The pragmatic answer is yes.
Basic life support saves the 'best' cardiac
arrest patients; any subsequent advanced
cardiac life support intervention has a
decreasing likelihood to restore spontaneous
circulation over time. Vasopressin should
therefore be employed rapidly if initial
epinephrine does not restore spontaneous
circulation. Our strategy is to alternate
between an initial injection of 1 mg
epinephrine i.v. and a subsequent injection
of 40 IU vasopressin i.v. every 3–5 minutes
during CPR “
Vasopressin combined with epinephrine during cardiac
resuscitation: a solution for the future?
Volker Wenzel Karl H Lindner
Department of Anesthesiology and Critical Care Medicine,
Innsbruck Medical University, Austria
Critical Care 2006, 10:125doi:10.1186/cc4846
Steroids
• Here we go again
• Methylprednisolone
– Enhances contractile function of heart during and after myocardial
ischemia
– Enhances contractile function of peripheral arteries during
endotoxemia
– Within 30 to 60 minutes
• Myocardial dysfunction and vasoplegia are key components
of post-resuscitation shock
Vasopressin, Epinephrine, and Corticosteroids for In-Hospital Cardiac Arrest
Mentzelopoulos, et al. Arch Internal Med; vol 1 Jan 12, 2009
• Single center, prospective trial 100 consecutive patients.
• 20 IU Vaso + 1mg Epi + 40mg Methylprednisolone and
Hydrocortisone taper vs. STD 1 mg Epi for up to 5 CPR cycles
• ROSC 81% vs. 52% p=.003
• Survival to D/C 30% vs. 0%
• Hymodynamics and Svo2 improved
• Less MOSF
• Independent of Induced Therapeutic Hypothermia
Monitoring
o General EMS capabilities
o
o
o
o
o
Pulse Oximetry
Capnography
EKG, Continuous Monitoring
Core Temperature
Mean Arterial Pressure Targets
o Advanced
o Biomarkers
Oxygenation
o 100% Oxygen
o Good for CPR/ROSC
o Bad post ROSC
o Hyperoxia in early reperfusion harms Post-Ischemic Neurons
o 100% FIO2 in 1st Hour post ROSC Worsened Outcome over
Immediate Adjustment to 94-96%
Ventilation
o Autoregulation is dysfunctional yet Cerebrovascular
Changes to PACO2 Preserved
o Hyperventilation may cause Vasoconstriction and Further
Ischemia
o Hypoventilation/Hypoxia/Hypercarbia elevates ICP and
Metabolic Acidosis
o Adjust Rate and Tidal Volume to keep PACO2 near Normal
Optimal Hemodynamics
o Balance Oxygen Delivery and Demands
o Should be Achieved in the Early Post Arrest Phase
o Optimize (Not Maximize)
o Preload
o PaO2
o Afterload
o Contractility
o Systemic Oxygen Utilization
Optimal Hemodynamics
o Post Cardiac Arrest Syndrome shares Characteristics with
Sepsis
o EGDT in Post Cardiac Arrest Syndrome
o Optimal MAP?
o > 100 mmHg w/i 5 minutes of ROSC Bad
o Cerebral perfusion dependant on MAP in Early Phase
o No Reflow Phenomenon may require 90-100 mmHg Range
o AMI or Myocardial Stunning maybe better at 65-75 mmHg Range
Optimal Hemodynamics
o Post Cardiac Arrest Syndrome shares Characteristics with
Sepsis
o EGDT in Post Cardiac Arrest Syndrome
o Optimal CVP 8 – 12 mmHg
o Relative Intravascular Volume Depletion Exists post ROSC
o Account for Pathologies causing Elevated CVP’s
o Cardiac Tamponade
o RV Infarct
o PE
o Tension PTX
Circulation Support
o Hemodynamic instability manifests as Dysrhythmias,
Hypotension, and poor Stroke Volume/Output
o Early Reperfusion is Best AntiArhythmic Therapy
o Optimize RV Filling Pressures 8 -12 mmHG
o 3.5 – 6.5 Lt First 24 hours
o Inotropes/Vasopressors After Volume Correction
o Pressor Dependence up to 72 hours
o Select Inotropes by BP, HR, CO, and SvO2
o Dopamine??
Therapeutic Hypothermia
o The Only Post Cardiac Arrest Therapy Show to Increase Survival
o Ongoing Evaluation of benefit in Patient Populations, Induction
Techniques, Target Temperature, Duration of Therapy, and
Rewarming Techniques.
o Benefit Related to Time of Initiation of Therapy
o Induction
o IV Fluids and Cooling Pads
o Maintenance
o Cooling Pads and Catheters
o ReWarming
Therapeutic Hypothermia
Sedation and Paralysis
o Indicated for Failure to return to Awake Status w/i 5-10
minutes Post ROSC
o Sedation reduces oxygen Consumption
o Opoids and Hypnotics Required
o EEG Monitoring for Sustained Neuromuscular Blockade
Seizures
o Increases Cerebral Metabolism 3 Fold
o Exclude ICH & Electrolyte Imbalance
o Myoclonus
o Difficult to Control
o Phenytoin Ineffective
o Clonazepam most Effective
o Improved Outcomes with Hypothermia despite Severe post
Arrest Status Epilepticus
Prognostication
o Pre-Cardiac Arrest Factors
o Many Factors Associated with Poor Outcome
o Advanced Age
o Race
o Poor Pre-Arrest health
o Diabetes
o Sepsis
o Metastatic cancer
o Renal failure
o Homebound Status
o Stroke
o APACHE II & III Scores
o None are Reliable Predictors
Prognostication
o Intra-Cardiac Arrest Factors
o Factors Associated with Poor ROSC
o Time To CPR
o Duration of CPR
o Quality of CPR
o Maximum ETCO2 < 10 mmHg
o Asystole
o Non cardiac Causes
o None are Reliable Predictors Post ROSC
Prognostication
o Post–Cardiac Arrest Factors
o Retention of Neurologic Function Immediately after ROSC
Best Predictor
o Absence of Neurologic Function Immediately after ROSC is
Not a Reliable predictor of Poor Outcome
o Reliable Predictors occur at 72 Hours
Prognostication
In the Age of Hypothermia
o Therapeutic Hypothermia Improves Survival and Functional
Outcome for 1 in every 6 Cardiac Arrest Survivors treated
(NNT=6)
o Alters Progression of Neurological Injury
o Changes the Evolution of Recovery
o Changes in Timing and Interpretations are Needed
o Do Not Withdraw Support Prematurely
Implementation
o Clinical Guidelines Don’t Change Practice
o Barriers
o Structural
o Human and Financial Resources
o Organizational
o Leadership
o Scientific
o Personal
o Intellectual
o Attitudinal
o Motivation
o Environmental
o Political
o Economic
o Cultural
o Social
Implementation
Protocol changes
drop/downplay Epi
Vasopressin early and repeat
accept Pox 96-98%
Follow eTCO2
Aim for MAP 65-95mmHg
Volume resuscitate
Dobutamine over Dopamine
Induce Hypothermia
Educate colleagues
Demand Outcomes
Transport to Resuscitation
centers
Questions
o What Will You Do Different Monday?