1. Therapeutic Hypothermia After Cardiac Arrest
Angelita Ramos, RN, BSN
Michelle Margerum, RN, BSN
Sonam Norbu, RN, BSN

2. Objectives Discuss cardiac arrest, therapeutic hypothermia (TH)
Review goals of therapy
Discuss guidelines of therapeutic hypothermia post- cardiac arrest, indications and contraindications
Discuss clinical evidence for TH
Discuss mechanism of action, pathophysiology of hypothermia post cardiac arrest
Review cooling methods/procedure
Review treatment protocols

3. Case Scenario TJ, a 65 year old African-American Male
Hx CAD, CHF, DM-type 2, HTN, COPD
Patient called 911 for SOB
Witnessed cardiac arrest at the scene with initial rhythm VTach
Defibrillated x2 with
ROSC
Intubated at the scene
Total down time 15 min

4. Case Scenario Cont. BP 100/50 HR 126 ST RR 12 SPO2 100% on 100% FiO2
GCS 5
Intubated
Head CT negative

5. To cool or not to cool
Does this patient meet the criteria for induced hypothermia post cardiac arrest ?????

6. Why should we cool

7. Cardiac Arrest Abrupt loss of cardiac function
Statistical Update
Out of hospital cardiac arrest (OHCA)
In hospital cardiac arrest (IHCA)
Incidence
Survival rate
2013
359,400
9.5%
209,900
23.9%
2012
382,800
11.45
23.1%
Abrupt loss of cardiac function
Cardiac arrest is the leading cause of death in North America
330,000 deaths per year in the US
Leading cause of neurologic injury
1/3rd of survivors have irreversible cognitive dysfunction
Erb, Hravnak & Rittenberger, 2012; AHA statistical Update, 2013

8. Cardiac Arrest
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9. Historical Perspective
Fourth and fifth century BC: Hippocrates advised snow and ice packing to reduce hemorrhage
1700: Dr. Currie used cold water therapy for the treatment of several clinical disorders
1803: Covering a patient with snow hoping for the resuscitation in Russia
1812: Hypothermia (HT) was used for numbing before limb amputation in Russia
1937: Dr. Fay adopted HT as an attempt to prevent cancer cells from multiplying

10. History Cont.
1950: Biglow introduced moderate hypothermia (28 °C to 32 °C) during cardiac surgeries in animals to protect the brain
1958: The first reported use of TH for comatose patients after cardiac arrest by use of HT as compared to normothermia
2002: Two prospective RCT were conducted in Australia and Europe of patients with anoxic brain injury after OHCA
2002: Recommendation of TH by the International Liaison Committee on Resuscitation (ILCOR) and subsequently the American Heart Association (AHA)

11. TH Post Cardiac Arrest
Inducing hypothermia in patients after ROSC following a cardiac arrest
Initiated ASAP with a target core temperature of 32° to 34° C for 12 to 24 hours
Decreases reperfusion injury
Preserves cerebral function
Decreases ischemic injury

12. AHA Guidelines
Post VF/VT arrest patients who are unresponsive with a ROSC after OHCA should be cooled to 32 to 34° C ( ° F) for 12 to 24 hours (Level of evidence Ib)
IHCA of any initial rhythms or OHCA with an PEA/asystole (Level of Evidence IIb)
Active rewarming should be avoided in comatose patients who spontaneously develops a mild hypothermia (>32 °C) during the first 48 hours after ROSC (Level of Evidence IIIc)

13. Inclusion Criteria for TH
Witnessed arrest
Post-cardiac arrest patient regardless of initial rhythm with ROSC within 60 min of initiation of ACLS
Within 6 hours following cardiac arrest
Maximum down time = 15 minutes
Comatose state GCS ≤ 5
Intubated

14. Exclusion Criteria for TH
Intracranial hemorrhage
Major surgery within 14 days
Severe systemic infection/sepsis
Preexisting coagulopathies
Pregnancy
DNR status/terminal illness
Drug induced coma
MAP <60mmHg for > 30 min after ROSC
Temperature < 30 °C (86F)
GCS > 5

15. Alternative Applications of TH
Traumatic brain injury
Acute liver failure
Aortic arch repair
Cardiac bypass surgery

16. Clinical Trials

17. Clinical Data The Hypothermia after Cardiac Arrest Study Group
Large randomized, controlled trial of 275 patients in nine centers in five European countries
Comparison of mild hypothermia (n=137) with standard normothermia (n=138) in patients in patients who suffered cardiac arrest due to ventricular fibrillation

18. Clinical Data Secondary Endpoints Primary Endpoint
Favorable neurologic outcome within six months after cardiac arrest
Pittsburgh cerebral-performance category of 1 (good recovery); 2 (moderate disability); 3 (severe disability); 4 (vegetative state), and 5 (death)
Overall mortality at six months and the incidence of complications during the first seven days
Severe bleeding; pneumonia; sepsis; pancreatitis; renal failure; pulmonary edema; seizures; arrhythmias; and pressure sores

19. Clinical Data-Treatment
All patients received standard intensive care per protocol
Patients randomly assigned to the hypothermia group were cooled to a target temperature of 32°C to 34°C with the use of an external cooling device
Temperature was maintained at 32°C to 34°C for 24 hours from the start of cooling
Followed by passive rewarming, over a period of 8 hours

20. Clinical Data-Results
A total of 75 of the 136 patients (55 percent) in the hypothermia group had a favorable neurologic outcome, as compared with 54 of the 137 (39 percent) in the normothermia group (risk ratio 1.40; 95 percent confidence interval, 1.08 to 1.81).
Mortality at six months was 41% in the hypothermia group and 55% in the normothermia group (risk ratio 0.74; 95% Confidence interval, 0.58 to 0.95)
The Hypothermia after Cardiac Arrest Study Group (2002). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. New England Journal of Medicine, 346(8), doi: /NEJMoa012689

21. Clinical Data
Cochrane Database review: systematic review and meta-analysis of RCT’s to assess the effectiveness of TH in patients after cardiac arrest
Main outcomes: neurologic outcome, survival, and adverse events
Conclusions: Mild TH improves survival and neurologic outcomes after cardiac arrest
The feasibility of TH in non-VF cardiac arrest has been confirmed, but studies have not yet shown a survival or neurological benefit
Poor prognosis associated with asystole is one possible reason for this observation
Arrich J, Holzer M, Havel C, Müllner M, Herkner H. (2012); Delhaye, C., Mahmoudi, M., & Waksman, R. (2011)

22. Pathophysiology and Mechanism of Action
ICE ICE BABY
Pathophysiology and Mechanism of Action

23. Hypothermia

24. Mild Hypothermia Moderate Hypothermia Severe
Confusion, impaired judgement, slurred speech
Tachycardia, ↑CO
Tachypnea
Cold diuresis
↑Hct, ↓platelet, WBC, ↑coagulopathy
Ileus, pancreatitis, gastric stress ulcers
↑ metabolic rate, hyperglycemia
Increased shivering
Lethargy, loss of pupillary reflex, EEG abnormalities
Progressive bradycardia, ↓CO, arrhythmias, J wave on ECG
Altered GI drug metabolism
↓metabolic rate, hyper-or hypoglycemia
Decreased shivering
Decline in EEG activity, coma, loss of ocular reflex
↓in BP and CO
VF and systole
Pulmonary edema, apnea
↓renal perfusion, oliguria, anuria
Patient appears dead, “pseudo-rigor mortis”
Kobeissi, Z., Zimmerman J. L. (2015). Hypothermia. In J.B Hall, G.A Schmidt, & J.P.Kress (Eds.), Principles of Critical Care, 4e.

25. Hypothermia

26. Mechanism of Action of TH
There are several hypothesis about the neuroprotective effects of TH
1954- hypothermia could lower cerebral oxygen consumption in dogs by ~ 7%
Abella, B. S., & Leary, M. ( 2015). Therapeutic hypothermia. In J. B. Hall , G. A. Schmidt, & J. P. Kress (Eds.). Principles of critical care, (4e).

27. Reperfusion Injury
Reperfusion injury occurs after restoration of oxygen to the brain
During reperfusion the immune system releases proinflammatory mediators: TNF-, interleukin-1, neutrophils, and macrophages
Leads to cell death
Therapeutic hypothermia can reduce the quantities and effects of these mediators
Lee, R. & Asare, K. (2010). Therapeutic hypothermia for out-of-hospital arrest. American Journal of Heath-System Pharmacy, 67,

28. MOA
This process leads to:
Accumulation of oxygen free radials
Activation of degradative enzymes
Cellular death
Therapeutic hypothermia helps to prevent this cascade of reactions by promoting cell membrane stability during oxygen deprivation
Lee, R. & Asare, 2010; Scirica, B. M. (2013)

29. Mechanism of Action

30. Reperfusion Injury
Reperfusion injury occurs after restoration of oxygen to the brain
During reperfusion the immune system releases proinflammatory mediators: TNF-, interleukin-1, neutrophils, and macrophages
Leads to cell death
Therapeutic hypothermia can reduce the quantities and effects of these mediators
Scirica, B. M. (2013). Therapeutic hypothermia after cardiac arrest. Circulation, 127,

31. Let the cooling BEGIN….

32. Treatment Protocols
Goal: Achieving the target temperature degrees C as quickly as possible.
Start cooling process ASAP.
For every hour delay to onset of cooling, mortality increased by 20%.
Can be achieved within 3-4 hrs of initiaing cooling.
Effective hypothermia treatment can be less than 24 hours if initiated rapidly after ROSC.
With long duration of cardiac arrest and delayed initiation of hypothermia, treatment for 48 hrs is needed to achieve good neurological outcomes.
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

33. Treatment Protocols
Preparation: Shivering, the body’s attempt at maintaining temp homeostasis, is a concern when trying to chieve a hypothermic state.
Do not actively rewarm patients who are spontaneously hypothermic
Treatment can be continued while in PCI laboratory and ICU
Place an arterial line early for BP monitoring
Continuous core temp monitor should be used: Esophageal, rectal or bladder temp
Several cooling system including liquid or get heat transfer and endovascular systems incorporate a temp probe
A secondary temp device should be used to monitor temp as well
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

34. Treatment Protocols Methods: Medication
Patient comfort and sedation:
Narcotic nalgesia-morphine or fentanyl
Sedation-midazolam or propofol
Paralysis to prevent shivering: Buspirone and meperidine
Train-of-four method
Cold saline infusion
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

35. Treatment Protocols
External cooling with cooling blanket or suface heat ex-change device
Eligibility should be confirmed, and materials should be gathered
Obtain 2 cooling blankets and cables
Alternatively, place heat-exchange pads on the patient
Pack the patient in ice (groin, axillae, side of neck)
Monitor VS and oxygen saturation
Once a temp below 34 degrees C is reached, remove ice bags, and the cooling blanket or heat-exchange device
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

36. Treatment Protocols Supportive therapy
A mean arterial pressure (MAP) goal of more than 80 mmhg is preferred from a cerebral perfusion standpoint.
Placing the head of the bed at 30 degrees.
Monitor the patient for arrhythmia associated with hypothermia
Hematolohic testing recommendation include:
CBC, Chem 7, PTT, troponin, and ABG
K+ values less than 3.5 mEq/L should be treated while patient is being cooled.
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

37. Treatment Protocols Supportive therapy (cont.)
Elevated serum glucose is deleterious to the injured brain.
PCO2 should be maintained in the reference range (35-45 mm Hg)
Skin care should be checked every 2-6 hrs for thermal injury caused by cold blankets.
Regularly check the patient’s temp with a secondary temp monitoring device when cooling.
Do not provide nutrition to the patient during initiation, maintenance, or rewarming phase of the therapy.
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

38. Treatment Protocols Controlled rewarming
Rewarming of the patient is begun 24 hrs after the initiation of cooling.
Rewarming phase may be the most critical, as constricted peripheral vascular beds start to dilate.
Peripheral hyperemia may cause hypotension.
Literature recommends rewarming slowly at a temp of degrees C every hour.
Rewarming will take approximately 8 hrs.
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

39. Cooling Methods Cooling methods include the following:
Surface cooling with ice packs
Suface cooling with blankets or surface heat-exchange device and ice
Surface cooling helmet
Internal cooling methods using catheter-based technoogies
Internal cooling methods using infusion of cold fluids.
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

40. Cooling Methods Surface cooling with ice packs
This method is inexpensive and represents an appropriate way to initiate cooling.
It can be messy and is less than optimal in the rate of cooling and target tem maintaenance.
In addition to ice packs, evaporate cooling fans has been used.

41. Cooling Methods
Suface cooling with blankets or surface heat-exchange device and ice
Conventional surface cooling balnkets are also suboptimal because of poor surface contact with the patient’s skin. However, a combination of water-circulating cooling device and ice packs
are effective at rapidly cooling patients
and are fair at maintaining target temp.

42. Cooling Methods Surface cooling helmet
The soft bonnetlike helmet contained a solution of aqueous glycerol that facilitated heat exchange.

43. Cooling Methods
Internal cooling methods using catheter-based technoogies
Two devices are currently available for use: Celsius Control System and Cool Line System. These technologies are also referred to as endovascular heat-exchange catheters. Heat exchange occurs between cooled saline that passes through the heat exchange portion of the catheter and the blood that flows over the outer surface of the catheter.
Endovascular cooling and rewarming is
reported to be faster and better at
maintaining target temperature.

44. Cooling Methods Internal cooling methods using infusion of cold fluids
Many have studied the effect of cold fluid infusion for the induction of mild-to-moderate hypothermia in humans.
The rates of induction are variable but otherwise considered to be rapid.
Cold fluid infusion with concomitant use of cooling blankets has also been shown to be efficacious.
Typical infusion volume is either 30 mL/kg or 2 L of fluid using either normal saline or lactated Ringer solution.

45. How to (BE) Cool? Cooling Procedure Set up cooling monitors
Monitor core temp: foley cath with temp probe or rectal temp probe
Cooling device
Internal: Alsius cooling catheter-set rate for max cooling, set target temp to 33 °C
External: turn down room temp, ice packs to neck, axilla, groin, torso, 2 cooling blankets-one above and one below the patient, set to 4° C
Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, Retrieved from

46. How to (BE) Cool? Cold IV therapy Medications
30 ml/kg of cold LR or NS 0.9% over mins ASAP post arrest
Will give 2.25 C temp reduction
Medications
For hypotension
500 cc NS 0.9% bolus q hr 3X doses for MAP below 70
Norepinephrine drip, titrate to keep MAP above 80
Dopamine drip, for MAP below 70, titrate to keep MAP mmHg
If need to increase CO
Dobutamine drip, titrate to maximum rate of 10 mcq/kg/min

47. How to (BE) Cool? Medications (cont) For comfort Sedation Shivering
Fentanyl IVP
Fentanyl drip
Morphine (monitor closely BP)
Sedation
Versed (use with caution in renal failure patient)
Propofol Drip
Shivering
Demerol
Nimbex – start at 3 mcq/kg/min, to maintain train of foru (TOF) 2/4
Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, Retrieved from

48. Stages of Therapeutic Hypothermia
Three phases of therapeutic hypothermia
Induction or initiation of cooling
Refers to the rapid cooling of the patient by means of either invasive or noninvasive techniques.
Maintenance
Refers to the period during which the patient is kept at the target temperature of 32 to 34 degrees C.
Rewarming or De-cooling
Begin 18 to 24 hrs after the initiation of cooling. May be passive or actively manage.
Erb, J.L., Hravnak, M., & Rittenberger, J., Therapeutic Hypothermia After Cardiac Arrest. American Journal of Nursing, 112 (7), 38-44

49. Induction Phase Obtained head CT
Record an initial temperatures - rectal is the best
Central line, peripheral IV or an intravascular cooling catheter
Baseline labs: CBC and electrolytes
Initiate sedation or paralytic medications
Shivering- must give sedation first!!!
Transfer appropriate critical care unit
Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, Retrieved from

50. Maintenance Phase
During the maintenance phase, controlling the patient’s temperature within the patient’s temp the target range: degrees C (core temp 33 degrees C)
Monitor blood glucose: mg/dl
Monitor BP MAP: mmHg
This phase can last up to hours
from the time the target temp is
reached (depending on facility protocol)
Suppress shivering!!!
Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, Retrieved from

51. Rewarming Phase
Rewarming begins 12 to 24 hours after the initiation of cooling.
Rewarm slowly at a rate of degrees C every hour
Remove cooling blankets (and all ice )
One method is to set the water temperature in the cooling device to 35°C, then increase the water temperature by 0.5°C every 1-2 hours until a stable core body temperature of 36°C has been reached for 1 hour
Maintain the paralytic agent and sedation until the patient’s temperature reaches 35°C
Monitor the patient for hypotension secondary to vasodilation r/t rewarming
D/C potassium infusion
Avoid hyperthermia
Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from

52. Potential Adverse Effects
Fluid and electrolytes imbalances
Arrhythmias
Insulin resistance
Shivering
Coagulation problems
Pain and sedation management
Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, Retrieved from

53. Summary

54. Conclusion
Studies have shown that therapeutic hypothermia is an effective method for improving neurologic outcomes of patients after out-of-hospital cardiac arrest after VF
The AHA/ILCOR states unconscious adult patients with spontaneous circulation 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.
Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest
Established guidelines can improve the quality of TH and effective post-resuscitation care

55. QUESTIONS

56. QUESTIONS
1. Hourly monitoring of blood glucose is recommended in the cooling phase because hypothermia leads to increased insulin resistance and decreased pancreatic activity leading to:
a. Hyperglycemia
b. Hypoglycemia
c. Normal blood glucose level
d. Unchanged glucose level
2. How does therapeutic hypothermia work in cardiac arrest?
a. It reduces the brain tissue oxygen demand and slows metabolism.
b. It increases intracellular acidosis and increase cerebral perfusion.
c. It increases the brain tissue oxygen demand and increases metabolism.

57. QUESTIONS Cont.
3. What has been shown to increase the survival after cardiac arrest?
Immediate recognition and activation of emergency response system, early CPR with emphasis on chest compression, rapid defibrillation, effective advanced life support, integrated post-cardiac arrest care including therapeutic hypothermia.
Therapeutic hypothermia, early CPR.
Early CPR with emphasis on chest compression, effective advanced life support.
4. What clinical manifestation would you not see with moderate hypothermia?
Decreased shivering
Loss of ocular reflex
Cold diuresis
Hallucinations

58. QUESTION Cont.
5. What is not an exclusion criterion for post-cardiac arrest therapeutic hypothermia?
DNR
Uncontrollable bleeding
Glasgow Motor Score < 5
Significant trauma
12 hours since return of spontaneous breathing

59. References
Abella B.S., Leary M (2015). Therapeutic Hypothermia. In Hall J.B., Schmidt G.A., Kress J.P. (Eds), Principles of Critical Care, 4e. Retrieved from Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from Arrich J, Havel C, Holzer M, Herkner H. Prehospital versus in-hospital initiation of mild therapeutic hypothermia for survival and neuroprotection after out-of-hospital cardiac arrest. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD DOI: / CD AHA Statistical Update, Heart Disease and Stroke Statistics-2-13 Update, A Report From the American Heart Association. Circulation, doi: /CIR.0B013E AD Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, Retrieved from Delhaye, C., Mahmoudi, M. & Waksman, R. (2012). Hypothermia therapy: Neurological and cardiac benefits. Journal of the American College of Cardiology, 59(3). doi: /j.jace Erb, J.L., Hravnak, M., & Rittenberger, J., Therapeutic Hypothermia After Cardiac Arrest. American Journal of Nursing, 112 (7), Field, J.M., Hazinski, M.F., Sayre, M.R., Chameides, L., Schexnayder, S.M., Hemphill, R., …Vanden Hoek., T.L., (2010). Part 1: Executive Summary. American Heart Association Guidelines on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, , doi: /CIRCULATIONAHA

60. References
Gardner,G., & MacDonald, S., Caring for Patients Receiving Therapeutic Hypothermia Post Cardiac Arrest in the Intensive Care Unit. Canadian Journal Of Cardiovascular Nursing, 23(3), 15-17
Field, J.M., Hazinski, M.F., Sayre, M.R., Chameides, L., Schexnayder, S.M., Hemphill, R., …Vanden Hoek., T.L., (2010). Part 1: Executive Summary. American Heart Association Guidelines on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, , doi: /CIRCULATIONAHA
Karnatovskaia, L.V., Wartenberg, K. E., & Freeman, W. D., (2014). Therapeutic Hypothermia for Neuroprotection. Neurohospitalist, 4(3), doi: /
Kobeissi, Z., Zimmerman J. L. (2015). Hypothermia. In J.B Hall, G.A Schmidt, & J.P.Kress (Eds.), Principles of Critical Care, 4e. Retrieved from
Lee, R. & Asare, K. (2010). Therapeutic hypothermia for out-of-hospital arrest. American Journal of Heath-System Pharmacy, 67, doi: /ajhp090626
Scirica, B.M. (2015). Therapeutic Hypothermia After Cardiac Arrest. Circulation, doi: /CIRCULATIONAHA
The Hypothermia after Cardiac Arrest Study Group (2002). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. New England Journal of Medicine, 346 (8), doi: /NEJMoa012689