1. HYPOTHERMIA POST CARDIAC ARREST 2011
M. Nelson January 2011

2. OBJECTIVES History Pathophysiology
Changes & Side Effects During Hypothermia
Indications/Exclusions
Overview of the UOHI Protocol

3. HISTORY
The concept of induced hypothermia in medicine has ebbed and flowed through the years. Benson et al (1959) studied hypothermia post cardiac arrest in humans and showed decreased mortality. Lack of sufficient evidence kept hypothermia from general acceptance.
Using mild hypothermia post cardiac arrest to preserve neurological function came to the forefront with the publishing of two landmark trials in the NEJM in 2002.

4. HISTORY
Both studies cooled out of hospital survivors of ventricular fibrillation and ventricular tachycardia arrests to 32°C-34°C for hours. They showed decreased mortality and improved neurological function.
After these studies were published, ILCOR and AHA recommended the use of therapeutic hypothermia post cardiac arrest. The beneficial results of these studies have subsequently been supported by other studies.

6. HISTORY
Despite this evidence, the use of hypothermia is limited at best even though survival of out of hospital cardiac arrest is very poor. Less than ½ of the victims who develop ROSC and survive to hospital leave the hospital alive and, in most cases, the cause of death is anoxic brain injury.

7. CARDIAC ARREST – WHAT HAPPENS?
ROSC
Depletes ATP in 4 min. failure of Na/K and Ca pumpscellular depolarization & injury
CEREBRAL BLOOD FLOW ALTERATION
first 5-30 minHyperemia
then cerebral hypoperfusion (about 50% of normal) for up to 12 hrs
ISCHEMIA
Activates inflammatory cascade – inflammatory cytokines likely contribute to cerebral edema
Lipolysis free fatty acidsfree oxygen radicalsApoptosis
Cerebral microvascular occlusions
from thrombi formed during arrest
Impaired cerebral reflow
ADDITIONAL NEURON DEATH

8. CARDIAC ARREST – WHAT HAPPENS?
Brain injury occurs at 2 time points:
Ischemia which activates multiple inflammatory and proapoptotic pathways
&
Reperfusion which increases neuronal injury by alterations in blood flow autoregulation, production of reactive oxygen species and more excitotoxic injury

9. CARDIAC ARREST – WHAT HAPPENS?
Reperfusion Injury

10. MANIFESTATIONS OF BRAIN INJURY
Coma
Seizures
Myoclonus
Cognitive dysfunction
Persistent vegetative state
Secondary Parkinsonism
Cortical or spinal stroke
Brain death

11. HYPOTHERMIA – HOW DOES IT WORK?
The many processes that cause brain injury are temperature dependant – fever stimulates the destructive pathways and mild to moderate hypothermia can block or mitigate these processes.
Other reasons for TH: severe traumatic brain injury, stroke, hepatic failure, spinal chord injury, and MI(in heart hypo may decrease area of injury, promote epicardial flow,  myocardial O2 demand, and preserve intracellular high energy phosphate stores.

12. PROTECTIVE EFFECTS OF MILD TO MODERATE HYPOTHERMIA.
Critical Care Medicine. Therapeutic Temperature Management: State of the Art in the Critically Ill. 37(7) Supplement:S186-S202, July 2009.
DOI: /CCM.0b013e3181aa5241

13. HYPOTHERMIA – THE PROCEDURE
The process of hypothermia involves cooling a patient to a prescribed temperature (32-34°C), for a period of time (12-24 hours) and then allowing the patient to rewarm or decool gradually.
The goal temperature, how quickly to cool, how to cool, how long to stay at target temperature, how slow to rewarm, these remain moving targets as further research becomes available.

14. HYPOTHERMIA – THE PROCEDURE
The 2005 American Heart Association guidelines regarding the use of hypothermia post cardiac arrest are summarized as follows:
Unconscious patients with ROSC after out-of- hospital cardiac arrest should be cooled to 32-34°C from hrs when the initial rhythm was VF (class lla)
May be beneficial for patients with non VF arrest or in-hospital arrest (class llb)
Hemodynamically stable patients post ROSC with spontaneous mild hypothermia should not be actively rewarmed

15. HYPOTHERMIA – THE PROCEDURE
Cardiac arrests from VF or VT have the most favorable results with hypothermia. Asystole and PEA are much less positive.
Most of the literature suggests cooling to a temperature of 33°C and to remain at that temperature for 24 hours.
Many animal studies have shown that starting cooling as soon as possible and attempting to reach target temperature quickly is the most effective procedure.

16. HYPOTHERMIA – THE PROCEDURE
However, many centres have had positive results even when the initiation of cooling and attainment of target temperature have been delayed. This suggests that hypothermia should be inclusive rather than exclusive and that other factors, such as age, likely play a role.

17. THE OTTAWA EXPERIENCE In 2008, the stats for Ottawa (pop.~ 900,000):
400 VSA patients in field due to cardiac arrest
61% had “cease resuscitation” order
39% were transported to the ED
18% continued resuscitation efforts in ED
14% were admitted to hospital
8% survived to discharge
Justin Maloney

19. HYPOTHERMIA – CHANGES & SIDE EFFECTS
Hypovolemia: from cold diuresis which can result in hypotension
Cardiovascular changes: BP, CVP, mixed venous saturation;  HR, CO
ECG changes: Bradycardia, PR & QT intervals, wide QRS complex; arrhythmias when temp 30°C (a.fib at 30°C, VT/VF at 28°C)
Electrolyte disorders: K, Mg, P, Ca (risk of hyperkalemia in warming)
HR is the factor most related to cardiac output (25-40% with TH). Generally, in metabolic rate is =or than the  in CO.
Myocardial contractility dependent on the HR – if HR allowed to  with T, systolic function usually  (may have mild diast. dysfcn. If artificially HR myocardial contractility decreases significantly.
CVP usually. systemic arterial resistance, slight in BP from vasoconstriction (but not in cerebral arteries) – this would theoretically help those patients who develop SIRS
ARRHYTHMIAS: don’t allow to go below 30. myocardium at deep hypo is less responsive to antiarrhythmics

20. HYPOTHERMIA – CHANGES & SIDE EFFECTS
Hypocoagulation/risk of bleeding: thrombocytopenia
Shivering: warming, O2 consumption, metabolic demands and intracranial pressure
Risk of Infections: inflammatory response is suppressed by cooling
Hyperglycemia: Hypothermia suppresses insulin release and causes insulin resistance
Skin Problems: from vasoconstriction, immobilization and immune suppression

21. HYPOTHERMIA – CHANGES & SIDE EFFECTS
Lab Changes: amylase, liver enzymes, lactate, ketonic acid, and glycerol; WBC & platelets; mild hematocrit; mild acidosis
Prolonged Drug Clearance: Delays metabolism & clearance of sedatives, NMBAs, anticonvulsants, & analgesics

22. INDICATIONS
Cardiac Arrest Patients with less than 30 minutes down time
Down time is defined as time of cardiac arrest to initiation of ACLS
Cardiac arrest patients who are not responding appropriately to verbal commands
Hemodynamically stable
VT, VF; consider PEA & Asystole

23. EXCLUSIONS Unwitnessed cardiac arrest with no CPR 15 minutes
More than 30 minutes from arrest to ACLS
Refractory shock despite treatment with IV fluids and vasopressors
Persistent or repeated episodes of cardiac arrhythmias
Refractory hypoxia (O2 sat less than 85% for more than 15 min despite adequate ventilation)
Severe coagulopathy with evidence of bleeding

24. METHODS OF COOLING Ice Packs Cooled IV fluids (4°C)
Trans Nasal Evaporative Cooling
Commercial Surface Cooling Intravascular Cooling Cooling
Methods aimed at convection and conduction to T.
Older pt tend to cool faster:less effective temp regulation
Younger patients need more opiates and sedatives
Obese patients will take more time to cool

25. UOHI PROTOCOL Patient Selection STEMI versus non STEMI Blood Work
Baseline assessment including VS, Neuro, Skin, RASS, TOF
Insert nasopharyngeal temperature probe, oral gastric tube & foley catheter
Central Venous Access & arterial line
Ensure second temperature source: foley, PA line, tympanic

26. UOHI PROTOCOL Set target temperature to 33°C
IV Sufentanil & IV Propofol
Neuromuscular blockade with IV Cisatacurium to maintain TOF at 2:4 and to suppress shivering
Maintain target temperature at 33°C for 24 hours
Temperature, VS, NVS (pupils), TOF q1h – maintain MAP of ≥ 65
Bedside Shivering Assessment Scale

27. UOHI PROTOCOL Monitor for frostbite q2h & prn Counterwarming as needed
Routine blood work: ABGs, K, Mg, glucose
IV/SC Heparin, IV Insulin, Artificial tears eye ointment
After 24 hours at target temperature, begin rewarming or “decooling”
Use Arctic Sun to warm 0.25°C per hour
Discontinue NMBA at start of warming
Rapid rewarming post cardiac surgery has been shown to jugular venous O2 sat indicating brain hypoxia – less jug desats are seen with slower rewarming

28. UOHI PROTOCOL
Maintain temperature  37°C for 48 hours after rewarming has begun
Continue sedation & analgesia till temperature is 36°C and TOF is 4:4
When TOF is 4:4, wean analgesia
Wean sedation last
Hyperthermia (T≥ 37.5°C) in the first 72 hours of ROSC is independently associated with a poor outcome regardless of the cause. Even with a mild T, more severe derangements of cerebrovascular reactivity has been seen

30. CHANGES & SIDE EFFECTS SHIVERING
Happens on induction at T of 35.5 and generally stops when temperature is  than 33.5
Older people tend to shiver less
Counterwarming: can help to lower the shivering threshold by countering the feedback loop from the skin temperature to the hypothalmic thermoregulation centre;
focal or body
Shivering in the awake patient can  O2 consumption by between %
Shivering has been linked to morbid cardiac events & adverse outcome if occurs in post op phase.

31. CHANGES & SIDE EFFECTS SHIVERING
To Block Or Not To Block: We have routinely used NMBA; problem has been that the TOF becomes unreliable so more difficult to titrate; Sedation and analgesia are needed even without NMBA
Pros
- very effective, does not cause hypotension
Cons
- Brain continues to try to make body shiver, may mask seizures, prolonged paralysis  risk of polyneuropathy
Must make sure patients are sufficiently sedated when using NMBA.
Loss of protective effect of hypo can be lost if patients are not adequately sedated (with or without NMBA)

32. CHANGES & SIDE EFFECTS SHIVERING Bedside Shivering Assessment Scale
0: None – no shivering
1: Mild – localized to neck/thorax, may only
be seen on ECG
2: Moderate – intermittent involvement of
upper extremities +/- thorax
3: Severe – generalized shivering or sustained
upper extremity shivering
Maintain Normal Magnesium Level

33. CHANGES & SIDE EFFECTS CARDIOVASCULAR Hypotension
We have not seen cold diuresis, hypotension has generally been due to cardiogenic shock prior to induction and vasodilation on rewarming
Ensure adequate fluid volume prior to rewarming
Arrhythmias
Bradycardia, bradycardia and more bradycardia
Usually we have not needed to treat; if have BP or MAP, or urine output, will treat with IV Dopamine
If want PA line & hemodynamics need to use iced injectate.

34. CHANGES & SIDE EFFECTS ELECTROLYTE DISORDERS & HYPERGLYCEMIA
Potassium & phosphate shift intracellularly during cooling and extracellularly during warming
Magnesium for shivering
IV Insulin continuous infusion is used frequently for glucose
HYPOCOAGULATION/BLEEDING
This has not been an issue for us even with the STEMI patients on Plavix and possibly IV Heparin

35. CHANGES & SIDE EFFECTS INFECTION
About 50% of our patients have developed pneumonia due to ?aspiration, VAP
Use rotation mode of the Total Care Bed, HOB at least 30 degrees, chlorhexidine mouthwash
We do not use prophylactic antibiotics
SKIN PROBLEMS
Pads are easy to get on & off to check
Positioning/rotation

36. CHANGES & SIDE EFFECTS PROLONGED DRUG CLEARANCE
May also have renal or hepatic dysfunction from prolonged cardiac arrest affecting metabolism & elimination for ? Amount of time
Use minimal doses for desired effect
Choice of drugs – which is best?

37. SEIZURES
Some form of continuous EEG monitoring is suggested especially if NMBA are used.
The other option is Bispectral Index
Monitoring.

38. QUESTIONS?

39. Bernard, S. (2009). Hypothermia after cardiac arrest
Bernard, S. (2009). Hypothermia after cardiac arrest. Critical Care Medecine 37(7Suppl.), S227-S233.
Chamorro, C.,et al. (2010). Anesthesia and analgesia protocol during therapeutic hypothermia after cardiac arrest: A systemic Review. Anesthesia and Analgesia 110(5),
Geocadin, R.G., et al. (2008). Management of brain injury after resuscitation from cardiac arrest. Neurologic Clinics 26,
Hirsch, K.G., et al. (2009). Management of brain injury after cardiac arrest. Continuum Lifelong Learning Neurology 15(3),
ILCOR Consensus Statement (2008). Post-cardiac arrest syndrome. Circulation 118,
Polderman, K.H., et al. (2009). Therapeutic Hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods. Critical Care Medicine 37(3),
Polderman, K.H. (2009). Mechanism of action, physiological effects, and complications of hypothermia. Critical Care Medicine 37(7 Suppl.), S186-S202
Seder, D.B. (2009). Methods of cooling: Practical aspects of therapeutic temperature management. Critical Care Medicine 37(7 Suppl.), S211-S222
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