1. Hypothermia Post Cardiac Arrest
Mazen Kherallah, MD, FCCP
Infectious Disease and Critical Care Medicine

2. Magnitude of Sudden Cardiac Arrest in the US
167,366
Stroke
450,000
Sudden cardiac arrest claims more lives each year than these other diseases combined
Sudden Cardiac Arrests
Lung Cancer
157,400
#1 Killer in the U.S.
One sudden death every 80 seconds
Breast Cancer
40,600
AIDS
42,156
1 U.S. Census Bureau, Statistical Abstract of the United States: 2001.
2 American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures 2001.
Heart and Stroke Statistical Update, American Heart Association.
4 Zheng Z. Circulation. 2001;104:

3. EMS systems have improved outcome of cardiac arrests

4. Survival Rates of Different Setting Cardiac Arrests
Internal Medicine Journal 34 ; 398  - July 2004
Critical care, 2001
Acta Anesthesiologica ,Aug 2006

5. Survival According to Initial Rhythm
Critical care medicine 1999

6. Outcome of cardiac arrest improved slowly over the years
Critical Care Medicine, 1999

7. Cerebral Energy Requirements
CMRO2: 3.5 cc O2/min/100 g
CMR glucose: 5.5 mg/min/100 g
Activation Metabolism
55-60%
Residual Metabolism
40-45%
60%
Barash 749, top left
40%
Barash, Cullen, Stoelting. Clinical Anethesia, 5th Ed. Lippincott Williams & Wilkins, 2006; p 751.

8. Global Ischemia

9. Ischemic
Cascade
CN 184
Cucchiara, Black, Michenfelder. Clinical Neuroanesthesia, 2nd Ed. Churchill Livingstone, 1998; p 184.

10. Neuro-Protection? Maintain blood flow
Maintain ATP levels by reducing CMR
Blocking Na and Ca influx
Scavenge free radicals
Block release/receptors for excitatory amino acids
Delay membrane failure & apoptotic processes
Inhibiting proteins that activate or contribute to damage (proteases, phospholipases, certain kinases)
Activating proteins that induce repair or rescue
Barash table 27-4, p 751
Barash, Cullen, Stoelting. Clinical Anethesia, 5th Ed. Lippincott Williams & Wilkins, 2006; p 751.

11. Hypothermia

12. Beneficial Effects of Hypothermia
Decrease in cerebral metabolism
Maintains integrity of membranes
Preserves ion homeostasis
Decreases excitatory AA release
Decrease Ca influx
Decrease lipid peroxidation
Decrease free radical formation
Decrease nitric oxide synthase activity
CN 202, CABG anes 2001

13. CMRO2 & Temperature
Miller. Miller’s Anesthesia, 6th Ed, Vol 1. Elsevier Churchill Livingstone, 2005; p 816.

14. Therapeutic Hypothermia Post Resuscitation

15. Therapeutic Hypothermia
1st reported use of therapeutic hypothermia in TBI in 1943.
1st reported use as a protective adjunct to neurosurgery in 1955.
IHAST

16. The Use of Hypothermia After Cardiac Arrest
Comatose survivors
Asystole or VF
31-32°C
Cooling until neurologic recovery (3 hours to 8 days)
Water-filled blanket
Benson DW, Williams GR Jr, Spencer FC, Yates AJ. Anesth Analg 1959; 38:

18. Michael Holzer N Engl J Med 2002;346:549-56
Vienna, Austria

19. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome After Cardiac Arrest (HACA)
Inclusions:
Exclusion:
Witnessed cardiac arrest,
Ventricular fibrillation or nonperfusing ventricular tachycardia
Presumed cardiac origin of the arrest
Age of 18 to 75 years
Estimated interval of 5 to 15 minutes from the patient’s collapse to the first attempt at resuscitation
Interval of no more than 60 minutes from collapse to restoration of spontaneous circulation.
Tympanic-membrane temperature below 30°C
Comatose state before the cardiac arrest
pregnancy
Response to verbal commands after ROSC
Evidence of hypotension; MAP< 60 mm Hg for more than 30 minutes after ROSC
Evidence of hypoxemia: O2 Sat <85% for more than 15 minutes after ROSC
Terminal illness that preceded the arrest
Preexisting coagulopathy.
The Hypothermia after Cardiac Arrest Study Group, . N Engl J Med 2002;346:

20. 275/3,551 (8%) Pts s/p Witnessed V-fib Arrest
Mild Therapeutic Hypothermia to Improve the Neurologic Outcome After Cardiac Arrest (HACA)
275/3,551 (8%) Pts s/p Witnessed V-fib Arrest
Multicenter RCT, Blinded assessment outcome.
Hypothermia (32-34 oC) x 24 hrs
137 Patients
normothermia (37-38 oC)
138 Patients
Primary endpoint: favorable neuro outcome* w/in 6 mo
Secondary: 6 mo mortality & 7 day complication rate.
* Pittsburgh cerebral-performance category, 1 [good recovery] or 2 [moderate disability]
The Hypothermia after Cardiac Arrest Study Group, . N Engl J Med 2002;346:

21. Bladder Temperature in the Normothermia and Hypothermia Groups
The Hypothermia after Cardiac Arrest Study Group, . N Engl J Med 2002;346:

22. Neurologic Outcome and Mortality at Six Months
The Hypothermia after Cardiac Arrest Study Group, . N Engl J Med 2002;346:

23. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome After Cardiac Arrest (HACA)
The Hypothermia after Cardiac Arrest Study Group, . N Engl J Med 2002;346:

24. Cumulative Survival in the Normothermia and Hypothermia Groups
The Hypothermia after Cardiac Arrest Study Group, . N Engl J Med 2002;346:

25. Bernard et al. N Engl J Med 2002; 346:557-563
Melbourne, Australia

26. Treatment of Comatose Survivors of OOH Cardiac Arrest with Induced Hypothermia
Multicenter rCT 77 Pts who remained unconscious s/p out of hospital cardiac arrest scene).
Randomized (by day) to hypothermia group (33 oC 2 hrs after return of spont circulation maintained for 12 hours) or normothermia.
Bernard, S. et al. N Engl J Med 2002;346:

27. Treatment of Comatose Survivors of OOH Cardiac Arrest with Induced Hypothermia
Bernard, S. et al. N Engl J Med 2002;346:

28. Favorable Neuro Outcome: Three Studies
Chi SquareTesting:
p <
308 Patients

29. Conclusion…
In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality.

30. ILCOR Advisory Statement
Unconscious adult patients with ROSC after out-of-hospital VF cardiac arrest should be cooled to 32°C - 34°C for hours
Possible benefit for other rhythms or in-hospital cardiac arrest
On the strength of these studies, the International Liaison Committee on Resuscitation published recommendations supporting the use of induced hypothermia after resuscitation from cardiac arrest. Given the large numbers of patients suffering cardiac arrest each year, even a small impact in survival and favorable neurologic outcome would lead to important gains for thousands of patients.

31. 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

32. How to apply hypothermia
It is not that complicated!!

33. Hypothermia Protocol Indications: Initiation: Degree of Hypothermia
Only comatose adults after ROSC who are “hemodynamically stable”
Initiation:
ASAP, but at least within 6 hours of event
Degree of Hypothermia
32-35oC core temperature
Duration:
At least 12 hours; 24 hours probably better

34. How to Cool: Four Modes of Heat Transfer
Conduction
Cold water immersion
Radiation
Cold room
Convection
Fans (do not use for infection control purposes)
Evaporation
Sweating

35. How to Cool: Hypothermia Protocol
Blanket cooling not effective in adults;
Intravascular cooling with bolus of iced RL or NS is effective
Surface SURFACE COOLING
SubZero, Aquamatic (conventional water-circulating)
Polar Air (forced air convection cooling)
Arctic Sun (“adhesive hyrogel, water circulating)
MTRE (tight wrap water circulating)

37. HOW TO COOL: Hypothermia Protocol
ENDOVASCULAR CATHETER COOLING
Radiant
Alsius
Innercool (metallic)

38. Monitoring: Mild/Moderate Hypothermia Protocol (33° C)
Endotracheal intubation
Sedation: fentanyl & midazolam
Paralysis: vecuronium 0.1 mg/kg PRN
Thermistors: bladder, rectal, esophageal, or blood temperature, ? Brain temperature
Radial artery and internal jugular lines
Intraparenchymal ICP & temperature monitor
Insulin drip for BS >180 mg/dl
Hypokalemia <3.4 mEq/l replaced

39. Monitoring: Mild/Moderate Hypothermia Protocol
ABGs at room temp (alpha-stat)
Vasopressors to keep CPP >70 mm Hg
ICP >20 mm Hg treated per protocol
Feedings held x 48 hours
Cultures/antibiotics as indicated
Passive controlled rewarming (0.5° / hr)
Active cooling is maintained at 36.5°C thereafter for 24 hrs to avoid “overshoot”
Need to adjust medications during hypothermia?

40. Example of Anti-Shivering Protocol
Focal Counterwarming
Feet and hands
Face
Body (Bear Hugger)
Buspirone 20 q8H
Meperidine mg q4H
Alt: dexmendetomidine, fentanyl, propofol
If use NMB, need to monitor EEG
Sub-clinical seizures may be more common than clinically recognized – should we load with anticonvulsants?

41. Detrimental Effects of Hypothermia
Circulatory: afterload, 3rd spacing, viscosity, diuresis, hypovolemia, hypotension
Cardiac: shivering, cardiac output, arrhythmias
Pulmonary: pulm edema
Neurologic: ICP w/ rewarming, affects neuromonitoring
Coagulation: plt dysfxn, fibrinolysis, bleeding
Metabolic: shifts O2 dissociation curve left, metabolic acidosis, respiratory alkalosis, Hypokalemia, hyperglycemia, ileus, drug metab
Immunologic: leuk mobility & phagocytosis
CN 202

42. Use of Therapeutic Hypothermia by Clinical Specialty
Critical Care
(n=33)
Cardiology
(n=64)
Emergency
Medicine
(n=109)
All respondents
(n=263)
Yes No
5% %
11% %
29% %
13% %
When broken down by specialty, respondents in Critical Care were most likely to have used this method of treatment, compared to respondents in Emergency Medicine or Cardiology (p<0.05).

43. Reasons Against Use of Hypothermia as a Therapeutic Tool
Reason for nonuse -
Percentage of respondents
0% % % % % %
Not enough data
49%
Haven’t considered it
32%
Not in ACLS guidelines
32%
When offered possible reasons why they had not used this modality
49% felt that there was not enough data
32% had not considered this treatment option
32% did not use it because it wasn’t part of ACLS guidelines
28% felt that cooling methods themselves presented an impediment – 19% felt that current methods were technically too difficult or cumbersome
9% felt that current methods were too slow to cool patients effectively.
Too technically difficult
19%
Current methods cool too slow 9%
Unsatisfactory initial attempts 4%

44. Cooling Technique Cooling technique Percentage of respondents
0% % % % % %
Cooling blankets
50%
Ice / cold liquid packing
15%
Ice / cold liquid gastric lavage
13%
Among physicians who had used therapeutic hypothermia, results showed that methods employed where consistent with recent publications on cooling as a treatment modality.
The published treatment techniques, namely cooling blankets or ice/cold liquid packing, were used by 65% of respondents.
Additionally, 13% of respondents used ice/cold liquid gastric lavage.
A further cohort of physicians (17%) reported use of “other methods”; for simplicity, our survey did not allow elaboration on this point.
IV cooling catheter 2% 2%
Cooling mist
17%
Other method

45. 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

46. Critical Care is A Promise
ان الله يحب العبد اذا عمل عملا أن يتقنه

47. If you are admitted to our ICU after cardiac arrest:
You will get cooled

48. كل نفس ذائقة الموت أجل كتاب لكل Thank You سورة آل عمران - آية 185
سورة آل عمران - آية 185
أجل كتاب لكل
سورة الرعد – آية38
Thank You