Therapeutic hypothermia after cardiac arrest May 6,2010 Damascus Ashraf Altarifi,MD,FCCP Consultant...
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Transcript of Therapeutic hypothermia after cardiac arrest May 6,2010 Damascus Ashraf Altarifi,MD,FCCP Consultant...
Therapeutic hypothermia after cardiac arrest
May 6,2010Damascus
Ashraf Altarifi,MD,FCCPConsultant 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.
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.
Outcome of in-hospital cardiac arrest National Registry of Cardiopulmonary Resuscitation (NRCPR)
of 14720 in-hospital arrests with 17% hospital discharge.
– 16% of patients had V Fib as initial rhythm with 34% hospital discharge
105 patients with in-hospital arrests reviewed.44% survived the arrest and 22% survived to discharge
Better prognosis
– Cardiac etiology
– V Tach or V Fib The only predictor of hospital survival was absence for need
of endotracheal intubations 76% of patients had good neurologic outcome (CPC 1)
Internal Medicine Journal 34 ; 398 - July 2004
Cardiac arrest in the ICU
Causes of arrest– Metabolic
disturbances 29%– Shock 26%– Hypoxemia 23%– Cardiac ischemia
11%– Brain death 7%– PE 2%
Initial rhythms– Asystole 47%– Brdycardia
followed by asystole 29%
– PEA 18%– V Fib/V Tach 6%
Hospital survival is 11%Critical care, 2001
Mode of death after admission to ICU post cardiac arrest
Intensive care medicine, 2004
0
10
20
30
40
50
60
70
80
MOFNeurologic complications
shock
VF/VT PEA/asyst
Cerebral performance categories after cardiac arrest
CPC 1 Good awake alert, May have mild psycho-cognitive dysfunction
CPC 2 Moderate awake, alert. May have weakness or dysarthria but able to do ADL.
CPC 3 Severe conscious, dependent on others. May have dementia or minimal communication
CPC 4 Coma Unconscious, Persistent Vegetative State
CPC 5 Brain death
Critical Care Medicine: Volume 24(2S) Supplement February 1996 pp 69S-80S
Overall performance after cardiac arrest
OPC 1 Good CPC 1,capable of normal life, no other organ disability
OPC 2 Moderate CPC 2 or disability from another organ dysfunction.Can work under special conditions.
OPC 3 Severe CPC 3 or severe disability from another organ. Dependent on others.
OPC 4 Vegetative Persistent Vegetative State OPC 5 Death
Critical Care Medicine: Volume 24(2S) Supplement February 1996 pp 69S-80S
Benson et al,Anesth Analg 1959; 38: 423-8.
Comatose survivors Asystole or VF 31-32°C Cooling until
neurologic recovery(3 hours to 8 days)
Water-filled blanket
0
10
20
30
40
50
60
Favorable neurologicrecovery
%
Hypothermia (n=12)
Normothermia (n=7)
The Use of Hypothermia After Cardiac Arrest
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
– Rewarming over 8 hrs
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549-556.
3351assessed
3246 ineligible
30Not included
275 enrolled
137hypothermia
138 normothermia
HACA Study Group
Neurologic outcome Pittsburgh cerebral performance category scale
Cerebral Performance Category (CPC)
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
Positive Outcomes
Negative Outcomes
Hypothermia for Coma After Cardiac Arrest
Hypothermia
Normothermia
P 0.02
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 = 192Normo = 179
Combined Data (3 studies)
Favorable Neuro– Hypothermia = 53%
(102/192)– Normothermia = 35% (63/116)
Chi Square Testing:
p < 0.0005
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 in-hospital 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
Interruption of Cerebral Blood Flow
Hypoxia-Ischemia
Resuscitation
Reperfusion Injury
Pathogenesis of Hypoxic-Ischemic Cerebral Injury
Mechanismsischemia
glutamate release
oxygen-free radicals
calcium shifts
mitochondrial dysfunction
reperfusion
excitotoxicity
inflam. cascades
Cell Death
blood brain barrier disruption & cerebral edema
hypothermia
lower metabolic rate
less oxygen consumption
Geocadin RG, Koenig MA, Jia X et al. Management of brain injury after resuscitation from cardiac arrest. Neurol Clin. 2008;22:487-506.
Effects of Hypoxia-Ischemia on Carbohydrate and Energy Metabolism-Anaerobic Glycolysis
Brain Glycogen Lactate production Phosphocreatine Brain Glucose ATP Tissue acidosis
HYPOTHERMIA: Mechanisms of Ischemic Neuroprotection
Profound reduction of active and basal cellular energy requirements
Reduced excitotoxic neurotransmitter release Reduced oxygen free radical production Improved BBB stability Decreased “ischemic depolarizations” in the
penumbra Protection against cytoskeletal proteolysis Decreased neutrophil infiltration Decreased cytokine and leukotriene production
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 12-
24h• Stop all sedation when normal body temperature is
achieved
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
Cold IV Fluids
Polderman 2005– 110 patients, 2-3L over
50 min– 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°CImprovements in MAP, renal function, no pulmonary edema
Polderman. Crit Care Med 2005;33:2744Bernard. 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?
Critical Care
(n=33)
Cardiology
(n=64)
Emergency
Medicine
(n=109)
All respondents
(n=263)
Yes No
5% 95%
11% 89%
29% 71%
13% 87%
Use of Therapeutic Hypothermia by Clinical Specialty
Not enough data
Haven’t considered it
Not in ACLS guidelines
Too technically difficult
Current methods cool too slow
Unsatisfactory initial attempts
0% 10% 20% 30% 40% 50%
Reason for nonuse- Percentage of respondents
49%
32%
32%
19%
9%
4%
Reasons Against Use of Hypothermia as a Therapeutic Tool
Cooling Technique
Cooling blankets
Ice / cold liquid packing
Ice / cold liquid gastric lavage
IV cooling catheter
Cooling mist
Other method
0% 10% 20% 30% 40% 50%
Cooling technique Percentage of respondents
50%
15%
13%
2%
2%
17%
Different ScenarioNew patient April 18
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 20 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