Post-resuscitation care of the
cardiac arrest survivor
David Seder MD
Maine Medical Center
Director of Neurocritical Care
Disclosures
• No financial conflicts
• ALL applications
described are offlabel!
• Grant support from
MMC NSI and MRC
http://www.neurocriticalcare.org
http://www.hypothermianetwork.com/INTCAR.htm
Epidemiology of OHCA
Circulation 2010;Jan 26:e12-13
• Cardiac arrest is common
– 295,000 OHCA per year in US
• 23% VF
• 31% Bystander CPR
– Median survival all rhythms 7.9%, VF 21%
– Prior to hypothermia
– Best EMS systems: ie: Seattle 1998-2001 (resuscitated)
• 17.5% survival to hospital discharge
• 34% VT/VF subgroup
– Since hypothermia (2006-2011 data)
– MMC 6 month survival with GNO
– Overall 30.6% (includes 55% PEA & Asystole)
– 58% VT/VF subgroup
– IHCA adults: 19% (despite 95% witnessed or monitored)
• A small increase in % survival
may result in a large increase in
the total number of hospitalized
patients…
3 Critical Interventions Save Lives
in Cardiac Arrest
• Bystander CPR
– Chest compressions only
• Minimally interrupted CPR by EMS
– “Cardiocerebral resuscitation”
• Ventilation kills
• Modern post-resuscitation care
– Therapeutic hypothermia
– Cardiac and hemodynamic support
From what do they die…?
Cause of Death in
OHCA
Cause of death in IHCA
9%
23%
51%
23%
68%
HIE
Cardiac
MOSF
26%
HIE
Cardiac
MOSF
Laver. Intensive Care Med 2004;30:2126
Mechanisms of brain injury in
circulatory arrest
• Primary Injury:
– “Energy failure” due to ATP depletion
• Secondary injury:
– Loss of transcellular electrolyte gradients
• Ca+, Na+, Cl- enter, K+ exits cell
• Water follows Na+ into cells causing cytotoxic edema
– Lipid peroxidases damage membranes
– Neurotransmitter release causes excitotoxicity
– Activation of apoptotic pathways
– Microvascular thrombosis
– Reperfusion injury
6-72h
Other secondary injury…
• Uncontrolled seizure activity
• Hypotension, hypoperfusion
– Postresuscitation syndrome
– ICP crisis
– Autoregulatory failure
•
•
•
•
Fever
Re-arrest
Hypoxia
Derangements of glucose
metabolism
Neurology 2008;72:744
Cardiac arrest associated brain
injury “CAABI”
• “No flow” affects the
most metabolically
active areas of brain
– Cortex
– Basal ganglia
– Cerebellum
• “Low flow” affects the
watershed areas
between vascular
territories
75 yo man OHCA 4-2010
• Unwitnessed arrest
• VF on EMS arrival
• 35 minutes CPR
and resuscitation
• Therapeutic
hypothermia
• 108h after ROSC,
GCS 4
• CMO at family
request
Shrunken eosinophilic neuron
(anoxic neuron) is the hallmark
of HIE
Pseudolaminar
necrosis
http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html
Anesthesia and Analgesia 1959;38 (6): 423
Anesthesia and Analgesia 1959;38 (6): 423
Clinical evidence for TH after CA
• Largest RCT of TH in
OHCA survivors
– 275 patients
randomized to TH or
routine care
– Europe 1996-2001
• Absolute 16% increase
in chance of a good
neurological outcome
• Absolute 14% decrease in
6 month mortality
N Engl J Med 2002;346:549-56
Clinical evidence for TH after CA
N Engl J Med 2002;346:549-56
Clinical evidence for TH after CA
New Engl J Med 2002; 346:557-63
• Australian
Randomized clinical
trial conducted 19961999
• Randomized on
alternating days to TH
or routine care
• TH: good outcome
49%, routine care
good outcome: 26%
(p=0.046)
Nonrandomized data
Polderman. Lancet 2008, 371:1955-1969.
Lausanne
• 55 VT/VF OHCA
treated with TH 20022004
• Compared to
historical controls
1999-02
• Similar DT, severity of
illness
• CPC 1-2: 56% vs.
26% pre-TH
Effect of the implementation of a therapeutic hypothermia protocol
on neurological outcome after out-of-hospital VF/VT arrest
-Crit Care Med 2006;34:1865
Acta Anaesthesiol Scand. 2009 Aug;53(7):926-34
Only 10% patients with OHCA
will meet RCT criteria for TH
•The decision to
initiate TH is usually
based on clinical
judgement of risk
and benefit, not on
proof!
Risks
• Infections
• Bleeding
• Need for
sedation
N Engl J Med 2002;346:549-56
Benefits
• Strongly neuroprotective
• Decreased mortality
• Better neurological
outcome
What are the risks?
• More infections
– Lung
• Trends toward
more bleeding*
• Electrolyte shifts
• Clinically
insignificant
bradycardia
• Changes in drug
metabolism
HCASG. NEJM 2002;346:549-56
TH after Cardiac Arrest
•
Clinical criteria for therapeutic hypothermia
–
No more than 8 hours have elapsed since the
return of spontaneous circulation.
Encephalopathy is present, typically defined as the
patient being unable to follow verbal commands.
There is no life-threatening infection or bleeding.
Aggressive care is warranted and desired by the
patient or the patient’s surrogate decision-maker
–
–
–
•
•
Terminal underlying disease
Impending cardiopulmonary collapse
If you use those criteria…
• VT/VF
– 46% of volume (MMC 2007-2010)
• Many patients are non-cardiac
• Outcomes are worse
• But some of those patients will do well…
Why treat all arrests?
• 28 yo woman
• 17 and 12 year old
admitted with massive
near-hanging patients
PE after long air flight
– Both treated in PICU
– IHCA – PEA
– Inter-arrest
thrombolysis
– 23 minutes of CPR
at MMC 2011
– Both extensor
posturing on ICU
admission
– CPC 1: receive
Christmas Card
annually
– Both CPC 1 on
hospital discharge
What do I treat with therapeutic
hypothermia?
• Cardiac Arrest
• Hepatic encephalopathy with cerebral
edema
• Near hanging
• Neonatal asphyxia
• Elevated ICP, all causes
• Severe (Hunt and Hess IV-V) SAH with
cerebral edema
Post-resuscitation care
• The brain injury is the leading cause of
death, and must be addressed,
but…
• Hemodynamic support is a critical element
of the neurological resuscitation
Postresuscitation syndrome
Curr Op Crit Care 2004;10:208-212
Myocardial dysfunction after CA
Kern. J Am Coll Cardiol 1996;28:232-40
Laurent. J Am Coll Cardiol 2002;40:2110-6
• Experimental model
• 10-15m arrest &
defibrillation
• Acute decrease in
LVEF
• Resolved with 48h
• In humans, echo
verifies this peaks at
24h, improves at 2448h.
In humans, hypotension after
CA is poorly tolerated
• 102 patients/1 year with
ROSC after CA
– Retrospective evaluation
• SBP < 100mmHg on two
episodes within first 6
hours independently
associated with death
– Careful correction for SOI
– OR 3.5 poor outcome
Resuscitation 2008;79:410-6.
•National Inpatient Sample
-1+ episodes of SBP<90 within
60 minutes ICU arrival
•Hypotension in first hour
independently associated
with death – OR death 2.69
Crit Care Med 2009;37:2895-903
Post-arrest hypertension in humans
• Retrospective review of 1,234 patients in
the Brain Resuscitation Clinical Trials
(BRCT) II and III databases
– Higher systolic pressure at 5, 10, 20, and 60
minutes was associated with good
neurological outcome
– Relationship preserved after controlling for
age, gender, arrest time, CPR time, and
comorbid conditions
Crit Care Med 1999;27(S):A29
ICP and CPP after CA
50.00%
46.4%
39%
45.00%
• 84 consecutive CA
survivors in Paris
received extradural
bolts
• High incidence ICP
and CPP crisis
• No patients with ICP
peaks over 25 mmHg
survived with GNO
40.00%
35.00%
30.00%
21.4%
25.00%
Day One
20.00%
15 . 0 0 %
10 . 0 0 %
5.00%
0.00%
ICP>15
80.00%
ICP>25
CPP<50
73.6%
70.00%
56%
60.00%
50.00%
40.00%
Day Two
26.3%
30.00%
20.00%
10 . 0 0 %
0.00%
ICP>15
ICP>25
CPP<50
Intensive Care Med 1991;17:392
BP Goals after CA
• Cerebral perfusion concerns balanced
against risks to the heart
• No randomized human data to support
inducing hypertension
• Europe tends to favor empiric MAP 80-90
• Blood pressure can be titrated to specific
hemodynamic endpoints, or to directly
measured CNS targets
Hyperoxia after Cardiac Arrest
• Project Impact
database 20012005
• 6326 patients
with cardiac
arrest
• Evaluated ABG
within 24h of the
arrest
JAMA 2010;303:2165
3 groups…
• First ABG
• Hypoxia:
– PaO2<60mmHg
• Normoxia
– PaO2 60299mmHg
• Hyperoxia
– PaO2>300mmHg
JAMA 2010;303:2165
Hyperoxia after Cardiac Arrest - 2
•
•
•
•
NZ/Australia
125 ICUs
Worst ABG
3 groups
– Hypoxia:
• PaO2<60mmHg
– Normoxia
• PaO2 60-299mmHg
– Hyperoxia
• PaO2>300mmHg
• 12,108 patients
– 73% hypoxia
– 15.9% normoxia
– 9.7% hyperoxia
Hyperoxia in post-resuscitation CA
care questioned!
• “Normoxic resuscitation”
• “Lowest FiO2 to generate an SpO2 of 95-99%
• Received consideration in new AHA and ACLS
guidelines
• Turn down the FiO2 if tolerated!
(but be careful)
Crit Care Med 2009;37 (Suppl):S211-S222.
How to cool…
Baltimore, 1955
Portland, Maine, 2006
Holzer. New Engl J Med 2010;363:1256-64
Basics of Therapeutic Hypothermia
• There are 3 phases of treatment:
– Induction
• Rapidly bring the temperature to 32-34C
• Sedate with propofol or midazolam during TH
• Paralyze to suppress heat production
– Maintenance
• maintain the goal temperature at 33C
• Standard 12-24 hours (optimal duration is unknown)
• Suppress shivering
– De-cooling (rewarming)
• Most dangerous period: hypotension, cerebral edema, seizures
• Goal is to reach normal body temperature over 12-24h
• Stop sedation when normal body temperature is achieved
Starting cooling early is better
• Start
cooling
ASAP!
• For every
hour delay
to onset of
cooling,
mortality
increased
by 20%!!
• 125 patients
randomized to
prehospital vs ED
cooling
• Good outcome in VT
pts cooled in the field
– 20/29 vs 10/22 (P=0.15)
• No safety concerns
• Average temp at ED
arrival differed by only
1ºC
Circulation. 2007;115(24):3064-70.
Cold IVF
• Polderman 2005
– 110 patients, 2-3L over 50’
– 36.9°C to 34.6°C, MAP
increased by 15mmHg,
no pulmonary edema
Bernard 2003
- 22 patients 30cc/kg LR at 4°C
over 30 min: 35.5°C to 33.8°C
Improvements in MAP, renal
function, no pulmonary edema
Polderman. Crit Care Med 2005;33:2744
Bernard. Resuscitation 2003;56:9
Cold IVF
• 2-3L of Ringers or Saline at 4C decreases
body temperature
– No effect on LVEF by echo
– Improved hemodynamic indices
Kim. Circulation 2005;112:715
Induction: how to cool
• Monitor core temperature
– Bladder, esophagus, or central venous/pulmonary
arterial
• Cold fluid
– 30cc/kg LR or 0.9%NS over 30 minutes
• 2-2.5C temperature reduction
– No adverse cardiovascular results
– Rare to cause pulmonary edema
• Ice packs and cooling mats
– Effective, but difficult to control rate of temperature
change
– Overcooling is dangerous
Induction: how to cool
• Commercial cooling devices
– Servo mechanism varies temperature of
circulating water or air (prevents overcooling)
– External (surface cooling) systems
• Hydrogel heat exchange pads
• Cold water circulating through plastic “suit”
• Cold water immersion – awaiting safety data
– Invasive (catheter based) systems
• Heat exchange catheter in SVC or IVC
• Plastic or metalic heat-exchange catheter
Shivering
• Drives up systemic
metabolic rate
– Increased CO2 production
– Increased O2 consumption
– Major cardiac stressor
• Drives up cerebral oxygen
consumption
– Favors ischemia
• Uncomfortable
Stroke. 2008 Dec;39(12):3242-7.
Management of shivering
• Neuromuscular blockade
– Must give sedation, first!!
– Vecuronium bolus 0.1mg/kg prn for shivering
• Meperidine or fentanyl
• Propofol
• Alpha blockade
– Dexmedetomidine infusion or clonidine
• Scheduled acetaminophen
• Focal counterwarming
• Magnesium infusion (serum level 3-4mg/dl)
De-cooling
• Vasodilation causes hypotension
– May require several liters IVF
• More shivering during this phase
• Inflammation increases at higher temperature
– “post-resuscitation” syndrome
• Increased ICP
• Watch for hyperkalemia
– Primarily problematic in renal failure
• SEIZURES
Hospital size and CA outcome
>109,000 patients
in the NIS
Mortality was lower at urban, teaching, and large hospitals
Intensive Care Med 2009;35(3):505-11
CA volume vs outcomes
• 4674 patients from 39
hospitals
• Overall mortality was
56.8%
– Not all patients comatose
• After adjusting for age
and severity of illness,
institutional mortality
ranged from 46% to 68%
• Annual case volume
strongly associated with
outcome
Resuscitation. 2009 Jan;80(1):30-4
CA System of Care
• Primary CA centers
– Initial cardiopulmonary
stabilization
– STEMI and neurological
evaluation
– Initiation of hypothermia
– Rapid transfer to
comprehensive center if
appropriate
– Function as a community
resource to train EMS, lay
public in bystander “hands
only” CPR
• Comprehensive CA centers
– Receive patients from primary
centers
– Therapeutic hypothermia
protocols, pathway,
equipment, expertise
– Cardiac revascularization and
advanced hemodynamic
support
– Neurology consultation and
EEG capacity
– Organ donation interface and
grief counseling
– Resource for primary centers
MaineHealth CA
Guideline
Summary (1)
• Basic care of the CA survivor in 2011
includes:
– Rapid consideration and early initiation of
therapeutic hypothermia
– Aggressive hemodynamic support including
PCI when appropriate
– Suppression of shivering and other AEs
– Treatment in an experienced center with
appropriate resources
Summary (2)
• Using an aggressive care paradigm
including therapeutic hypothermia,
hemodynamic support, and quality ICU
care, can expect better OHCA outcomes
– All rhythms: 30-40% good neurological
outcome
– VT/VT: 50-65% good neurological outcome
– PEA/Asystole 13-25% good neurological
outcome
Discussion
Horstmann et al. Brain
atrophy in the aftermath of
cardiac arrest. NEUROLOGY
2010;74:306-312
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