Therapeutic Hypothermia after Cardiac Arrest
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Transcript Therapeutic Hypothermia after Cardiac Arrest
Therapeutic hypothermia
after cardiac arrest
April 19,2013
Khartoum-Sudan
Ashraf Altarifi,MD,FCCP
Consultant Intensivist and Pulmonologist
King Faisal Specialist Hospital and Research
Center
Riyadh, Saudi Arabia
Case presentation
65 year old male patient with hx of
DM,HTN was found unresponsive at
home
Patient taken to ER, found to be in
asystole.
Patient intubated, CPR done for 25
minutes with return of pulse and blood
pressure. Pt in sinus rhythm but
requiring inotropes.
Neuro exam
Pt unresponsive, pupils non reactive.
No spontaneous movements in arms
or legs.
2 hours later ,Pt develops myoclonic
jerks.EEG negative for seizures.
Patient started on sedation
Common Scenario!
Three weeks later patient remained
comatosed in a persistent vegetative
state.GCS 4/15.Tracheostomy done.
Patient develops ventilator associated
pneumonia.
Patient develops respiratory failure,
septic shock, and renal failure.
Patient dies 27 days after the initial
cardiac arrest.
Magnitude of Sudden
Cardiac Arrest in the US
Stroke
Lung Cancer
Breast Cancer
AIDS
167,366
157,400
40,600
42,156
Sudden
cardiac
arrest
claims more
lives each
year than
these other
diseases
combined
450,000
Sudden
Cardiac
Arrests
#1 Killer in
the U.S.
Cardiopulmonary resuscitation on TV
97 episodes of ER, Chicago Hope and Rescue
911 reviewed
60 incidents of Cardiac arrest observed
Etiology of cardiac arrest 55% trauma,28%
cardiac
75% of patients survived the immediate arrest
68% survived to hospital discharge
10 cases had miraculous recovery when
physicians gave up hope.
Almost all patients surviving had normal
neurolgic and functional outcome.
NEJM 1996 :334 (1578-82)
Real life outcome of cardiac
arrests
Survival usually defined as survival to
hospital discharge.
Varies greatly between different EMS
systems.
Varies according to downtime prior to
resuscitation.
Varies according to initial rhythm.
Epidemiology of Out of
Hospital cardiac arrests
• Cardiac arrest is common
– 295,000 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 Circulation 2010;Jan
26:e12-13
EMS systems have improved
outcome of cardiac arrests
3 Critical Interventions
Save Lives in Cardiac Arrest
Bystander CPR
– Chest compressions only
Minimally interrupted CPR by EMS
– “Cardiocerebral resuscitation”
Modern post-resuscitation care
– Therapeutic hypothermia
– Cardiac and hemodynamic support
From what do they die…?
Cause of Death in
OHCA
9%
Anoxic
brain
damage
Cardiac
23%
68%
Cause of death in IHCA
51%
23%
Anoxic
brain
damage
Cardiac
26%
MOSF
MOSF
Laver. Intensive Care Med 2004;30:2126
Cerebral performance
categories after cardiac arrest
CPC 1
Good
CPC 2
Moderate
CPC 3
Severe
CPC 4
Coma
CPC 5
Brain death
awake alert, May have
mild psycho-cognitive
dysfunction
awake, alert. May have
weakness or dysarthria
but able to do ADL.
conscious, dependent on
others. May have
dementia or
minimal communication
Unconscious, Persistent
Vegetative State
Critical Care Medicine: Volume 24(2S) Supplement February 1996 pp 69S-80S
Overall performance
after cardiac arrest
OPC 1
OPC 2
OPC 3
OPC 4
OPC 5
Good
CPC 1,capable of normal
life, no other organ disability
Moderate CPC 2 or disability from another
organ dysfunction.Can work
under special conditions.
Severe
CPC 3 or severe disability from
another organ. Dependent on
others.
Vegetative Persistent Vegetative State
Death
Critical Care Medicine: Volume 24(2S) Supplement February 1996 pp 69S-80S
Can the outcome of
cardiac arrest be
improved?
Anesthesia and Analgesia 1959;38 (6): 423
The Use of Hypothermia After Cardiac Arrest
60
Comatose survivors
Asystole or VF
31-32°C
Cooling until
neurologic recovery
(3 hours to 8 days)
Water-filled blanket
50
40
% 30
20
10
0
Favorable neurologic
recovery
Hypothermia (n=12)
Normothermia (n=7)
Benson et al,Anesth Analg 1959; 38: 423-8.
Mild Therapeutic Hypothermia to
Improve the Neurologic Outcome
After Cardiac Arrest (HACA)
Patients with witnessed cardiac arrest from VF
or pulseless VT, 18-75 years of age, estimated
5-15 minutes to attempted resuscitation, and
less than 60 minutes from collapse to
restoration of spontaneous circulation (ROSC).
275 patients of 3,551 cardiac arrests screened
were eligible for the study (8%)
137 patients randomized to receive
hypothermia (32-34°c) for 24 hours
Dr. Fritz Sterz, Vienna, Austria, and The Hypothermia After Cardiac Arrest
Study Group, N Engl J Med 2002; 346:549-556
HACA Study Group
Randomized trial 2002 -Hypothermia vs
Normothermia
Methods
– Inclusion - OOHCA due to VF
– Exclusion – Cardiogenic shock
Hypothermia group
– 32°C - 34°C
– Cooled for 24 hrs
3246
ineligible
3351
assessed
30
Not included
137
hypothermia
275
enrolled
138
normothermia
– Rewarming over 8 hrs
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac
arrest. N Engl J Med. 2002;346:549-556.
HACA Study Group
Neurologic outcome
Pittsburgh cerebral performance category scale
Cerebral Performance Category (CPC)
Positive
Outcomes
Negative
Outcomes
CPC 1
Good cerebral performance
CPC 2
Moderate cerebral disability
CPC 3
Severe cerebral disability
CPC 4
Coma or vegetative state
CPC 5
Brain death
HACA study: results
Bladder Temperature in the Normothermia and Hypothermia Groups.
Hypothermia for Coma After Cardiac Arrest
P 0.02
Hypothermia
Normothermia
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac
arrest. N Engl J Med. 2002;346:549-556.
Mild Therapeutic Hypothermia to
Improve the Neurologic Outcome
After Cardiac Arrest (HACA)
Mortality at 6 months was 41% in the
hypothermia group and 55% in the
normothermia group
55% of hypothermia group and 39% of
normothermia group had a favorable
neurologic outcome (good recovery or
moderate disability) p value 0.009
Complication rate did not differ
significantly between the two groups
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac
arrest. N Engl J Med. 2002;346:549-556.
Treatment of Comatose Survivors
of OOH Cardiac Arrest with
Induced Hypothermia
77 patients with cardiac arrest due to VF,
with ROSC but coma, randomized to
hypothermia or normothermia
Patients excluded if the age of men was
less than 18, and women less than 50, or
cardiogenic shock
Hypothermia to 33 degrees begun within
two hours and continued for 12 hours with
cold packs.
Bernard et al,N Engl J Med 2002; 346:557-563
Treatment of Comatose Survivors of
OOH Cardiac Arrest with Induced
Hypothermia
Survival was 21/43 of the hypothermia
group (49%) vs. 9/34 treated with
normothermia (25%) p = 0.01
Good outcome (normal or with minimal
or moderate disability) was 49% in
hypothermia group and 26% in the
normothermia p = 0.046
Bernard et al. (Australia), N Engl J Med 2002; 346:557-563
Favorable Neuro Outcome
:All three studies combined
Benson 1959
– 50% with Hypo (12)
– 15% with Normo (7)
HACA 2002
– 55% with Hypo (137)
– 39% with Normo (138)
Bernard 2002
– 49% with Hypo (43)
– 25% with Normo (34)
Total patients:
Hypo = 192
Normo = 179
Combined Data (3 studies)
Favorable Neurologic outcome
– Hypothermia
– Normothermia
p < 0.0005
=
=
53% (102/192)
35% (63/116)
ILCOR Advisory Statement
Unconscious adult patients with ROSC
after out-of-hospital VF cardiac arrest
should be cooled to 32°C - 34°C for 12 - 24
hours
Possible benefit for other rhythms or inhospital cardiac arrest
2005 AHA guidelines for ACLS
and post CPR care
In a select subset of patients who were initially
comatose but hemodynamicaly stable after a
witnessed VF arrest of presumed cardiac
etiology, active induction of hypothermia was
beneficial. Thus, unconscious adult patients
with ROSC after out-of-hospital cardiac arrest
should be cooled to 32°C to 34°C for 12 to 24
hours when the initial rhythm was VF (Class
IIa). Similar therapy may be beneficial for
patients with non-VF arrest out of hospital or for
in-hospital arrest (Class IIb).
2005 AHA guidelines, Circulation, 2005
Possible mechanisms for
clinical benefit
Pathogenesis of Hypoxic-Ischemic Cerebral Injury
Interruption of Cerebral Blood Flow
Hypoxia-Ischemia
Resuscitation
Reperfusion Injury
Mechanisms
hypothermia
lower
metabolic rate
less oxygen
consumption
reperfusion
ischemia
glutamate
release
excitotoxicity
inflam. cascades
calcium
shifts
mitochondrial
dysfunction
oxygen-free
radicals
Cell Death
blood brain barrier
disruption & cerebral
edema
Geocadin RG, Koenig MA, Jia X et al. Management of brain injury after resuscitation
from cardiac arrest. Neurol Clin. 2008;22:487-506.
How to apply
hypothermia
It is not that
complicated!!
Four Modes of Heat Transfer
Conduction
– Cold water immersion
Radiation
– Cold room
Convection
– Fans (do not use for infection control
purposes)
Evaporation
– Sweating
Basics of Therapeutic
Hypothermia: Three 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
– Rewarming
• Most dangerous period: hypotension, brain swelling,
• Goal is to reach normal body temperature over 1224h
• Stop all sedation when normal body temperature is
achieved
Induction: how to cool
Commercial cooling devices
– External (surface cooling) systems
• Hydrogel heat exchange pads
• Cold water circulating through plastic “suit”
• Cold water immersion : ? safety data
– Invasive (catheter based) systems
• Heat exchange catheter in SVC or IVC
• Plastic or metalic heat-exchange catheter
Devices
Medivance ARCTIC SUN
Cold IV Fluids
Polderman 2005
Bernard 2003
– 110 patients, 2-3L over
50 min
– 36.9°C to 34.6°C, MAP
increased by
15mmHg, no
pulmonary edema
- 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
Maintainance: how to cool
Monitor core temperature
– Bladder, esophagus, or central
venous/pulmonary arterial
Ice packs and cooling mats
– Effective, but difficult to control rate of
temperature change
– Overcooling is dangerous
Endovascular cooling allows for gradual
reduction in temp, maintainence at desired
temp and prevents over cooling
Management of shivering
Neuromuscular blockade
– Vecuronium bolus 0.1mg/kg prn BSAS>2
– Cisatricurium in renal failure
Propofol
Alpha blockade
– Dexmedetomidine infusion or clonidine
Scheduled acetaminophen, buproprion
Meperidine or fentanyl
Focal counterwarming
Magnesium infusion (serum level
3mg/dl)
Re-warming
If using surface cooling: Use passive re-warming
Remove Ice packs
Stop cold IV fluids
If using endovascular cooling: set temperature
rise at 0.3-0.5 degrees per hour
Avoid rapid re-warming
Re-warming
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
Side Effects of hypothermia
Toxicity increases with increased duration &
intensity of cooling
Four categories of toxicity:
– Cardiovascular
• Arrhythmia
– Hematologic
• Platelet dysfunction, coagulopathy
– Immunologic
• Impaired neutrophil function leading to increased infection
– Metabolic
• Hypokalemia, hyperglycemia, ileus, pancreatitis
• Re-warming: SIRS physiology?
Hypothermia Questions
How quickly?
– ASAP, but at least within 6 hours of event
– Longer the delay, the longer hypothermia must be
continued to provide protection
How cold?
– At least 35oC core temperature but not lower than 32oC
– Temp < 30 degrees leads to more complications
How to cool? Use NSAID?
– Blanket cooling not effective in adults; intravascular
cooling with bolus of iced RL or NS is effective
– Selective head cooling may benefit neonates
Hypothermia Questions
How long to cool?
– At least 12 hours; 24 hours probably better
How to rewarm?
– Worse outcome if rewarm rapidly
– Management of shivering/stress response
Which patients should be cooled?
– Only comatose adults after ROSC who are
“hemodynamically stable”
– Should cooling start in the field or at the referring
hospital?
Hypothermia Questions
How to monitor cooling?
– Bladder, rectal or blood temperature? Brain
temperature?
How should we manage shivering?
– If use NMB, need to monitor EEG
– Sub-clinical seizures may be more common than
clinically recognized – should we load with
anticonvulsants?
How to adjust medications in the hypothermic
patient
Are there useful biomarkers?
Use of Therapeutic Hypothermia
survey
Yes 13%
No 87%
Use of Therapeutic Hypothermia
by Clinical Specialty
Yes
Critical Care
29%
(n=33)
Cardiology
(n=64)
No
71%
11%
89%
5%
95%
Emergency
Medicine
(n=109)
All respondents
(n=263)
13%
87%
Reasons Against Use of
Hypothermia as a Therapeutic Tool
Reason for nonuse-
Percentage of respondents
0%
Not enough data
10%
20%
30%
40%
50%
49%
Haven’t considered it
32%
Not in ACLS guidelines
32%
Too technically difficult
19%
Current methods cool too slow
9%
Unsatisfactory initial attempts
4%
Cooling Technique
Cooling technique
Percentage of respondents
0%
Cooling blankets
Ice / cold liquid packing
Ice / cold liquid gastric lavage
IV cooling catheter
Cooling mist
Other method
10%
20%
30%
40%
50%
50%
15%
13%
2%
2%
17%
KFSH Hypothermia protocol
Different Scenario
New patient March 12
55 year old male s/p gastric bypass surgery with
hx of pyloric stenosis
Massive aspiration leading to respiratory then
cardiac arrest.
CPR done for 14 minutes
Pt admitted to ICU. Hypothermia protocol
applied
Within 48 hours, pt fully awake, follows
commands
Extubated day 5.
Take home messages
Strong evidence that mild hypothermia
is neuro-protective after return of
spontaneous circulation.
Fever is detrimental post resuscitation
(and for any neuro patient)
Hypothermia is underutilized so far but
should be included in post resuscitaion
care of cardiac arrest victims
Thank you
CHAIN OF SURVIVAL
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