259-L01 Therapeutic Hypothermia Post Cardiac Arrest · 2014. 12. 2. · hypothermia post cardiac arrest. • Learning Objectives 2: Breakdown and evaluate the pharmacotherapy considerations

Update in Therapeutic Hypothermia Post Cardiac Arrest

Allison Forni, PharmD, BCPSClinical Pharmacy Specialist

UMass Memorial Medical Center, Worcester MA

Learning Objectives

• Learning Objective 1: Describe controversies on who, how, and when to initiate therapeutic hypothermia post cardiac arrest.

• Learning Objectives 2: Breakdown and evaluate the pharmacotherapy considerations for patients requiring therapeutic hypothermia.

Patient Case

• AS is a 92 yo male suffering a cardiac arrest at SNF due to respiratory failure. The patient was down for unknown period of time. Bystander CPR was initiated, EMS arrived 4 minutes after call, presenting rhythm was asystole. Patient received 1 round of epinephrine and atropine and had ROSC 5 minutes after EMS arrival. Patient transferred to BWH ED, initial GCS 3 (no sedatives given), in sinus tachycardia.

What elements of this patient case make the application of TH

controversial?

Cardiac Arrest

Loss of cerebral perfusion

Anaerobic glycolysis

Depolarization

ATP depletion, intracellular acidosis

Normalization of blood flow

Free oxygen radical

generation

Inflammatory response

Ischemic Insult Reperfusion

Targeted Temperature Management (TTM) as a treatment modality for cardiac arrest

• History

• Clinical practice of TTM should specify:• A description of the

intended temperature profile

• The thermoregulatory interventions used to achieve the target

• The actual performance of the TTM strategy

• The primary and secondary outcomes that the TTM intended to achieve

Temperature Effect

36°C Increased activity attempting to warm up, skin pale, numb, and waxy, muscles tense, fatigue, and signs of weakness.

34°C–35°C Uncontrolled intense shivering, still alert but movements uncoordinated, and pain and discomfort due to coldness.

31°C–33°C Shivering slows or stops, muscles stiffen, mental confusion, apathy, speech slowed and slurred, breathing slower and shallow, and drowsiness.

31°C Skin cold, pupils dilated, extreme weakness, slurred speech, exhausted, denies problems, resists help, gradual loss of consciousness,and progressive respiratory arrest and arrhythmias.

Nunnally ME. CCM 2011; 29(5): 1113‐1125

2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest

© 2014 American Society of Health-System Pharmacists 1

Rationale for TTM

• Post‐ischemic effects are temperature dependent

• Increased temperature enhances harmful effects of free radicals and activates NMDA receptors

Peberdy MA et al. Circulation 2010, 122:S768‐S786Nunnally ME et al. CCM 2011; 29(5): 1113‐1125Castren M, et al. Acta Anaesthesiol Scand 2009; 53: 280‐288.

Critical Care Consensus Recommendations:“The jury STRONGLY RECOMMENDS targeted

temperature management to a target of 32°C–34°C as the preferred treatment (vs. unstructured temperature management) of out‐of‐hospital adult cardiac arrest

victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular

tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation,

moderate quality of evidence).”

AHA recommendation:“We recommend that comatose (ie, lack of

meaningful response to verbal commands) adult patients with ROSC after out‐of‐hospital VF cardiac arrest should be cooled to 32°C to 34°C (89.6°F to 93.2°F) for 12 to 24 hours (Class I, LOE B). Induced hypothermia also may be considered for comatose adult patients with ROSC after in‐hospital cardiac arrest of any initial rhythm or after out‐of‐hospital cardiac arrest with an initial rhythm of pulseless electric activity or asystole (Class IIb, LOE B).”

Physiologic effects of TTM

Protective• Reduce cerebral metabolism

• Reduce cerebral blood flow

• Reduce ion pump dysfunction and neuroexcitation

• Reduce mitochondrial injury

• Decrease intracellular acidosis and intracranial hypertension

• Decrease free radical production

• Decrease apoptosis

Deleterious• Cardiovascular effects

• Glucose and electrolyte abnormalities

• Reduction in GI motility

• Coagulopathy

• Immunosuppression

Bernard SA, et al. NEJM 346: 557‐563. 2002;

Side Effects of TTM

Biochemical and Hematologic Values

Urine output

Electrolyte loss

Insulin secretion

Insulin sensitivity

Creatinine Clearance

Platelet count

Platelet aggregation

Infection

Cardiac Effects

VT/VF

Cardiac Output

Bradycardia

HACA Investigators. NEJM 2002; 346(8): 549‐556.

Patients 275 enrolledDifferences= DM, CV disease, bystander CPRExclusion Criteria

77 randomizedNo differences in baseline characteristicsExclusion Criteria

Intervention 32-34ºC by bladder temp with surface cooling over 24hrs (cooled over 4hrs, warmed over 8hrs)

33ºC within 2 hrs of ROSC and maintained for 12hrs with active rewarming over 6 hrs

Endpoints Primary= favorable neurologic outcome at 6 months

Primary= neurologic outcome at discharge

Bernard SA, et al. NEJM 346: 557‐563. 2002.

Randomized Controlled Trials

Patient Case


What else do you want to know about

this patient?

Is this patient a candidate for TH?



Who

What

When

How

Why

Patient Selection

• Variability in:

• Initial rhythm

• Witnessed vs unwitnessed

• In hospital vs out of hospital

• Time to BLS

• Total ischemic time

Comatose lack of meaningful response to verbal commands

Return of spontaneous circulation

McNicol DR et al. Circulation 2012; 26(21) Supplement

• Time since ROSC

• Baseline body temperature

• Etiology of arrest

• Hemodynamic parameters

• Exclusion criteria

HACA Investigators. NEJM 2002; 346(8): 549‐556.

Complications during THWho

What

When

How

Why

Time Course of TH

• Time to initiation

• Time to achievement of target temperature

Nielsen N et al. Acta Anaesthesiol Scand 2009; 53: 926‐943Wolff B et al. International Journal of Cardiology 2009; 133: 223–228

Goal: To reduce the patient’s body temperature to goal as quickly as possible• Rapid induction reduces risk for side

effects• Patient management problems

Goal: To tightly control the patients core body temperature with a maximum fluctuation of 0.2‐0.5º Celcius• Increased stability of the patient

but longer‐term side effects

Induction Maintenance Reversion

Polderman KH, et.al Critical Care Med 2009.37(3);1101‐1120.

Maintain controlled

normothermia

Goal: To rewarm the patient in a slow and controlled fashion at 0.2 to 0.5 º Celsius per hour Risks associated with speed of

rewarming

? hrs0 hrs ? hrs

Duration of TH



Who

What

When

How

Why

Timing of TH

In hospital vs out of hospital

Out‐of hospital patients are generally well or at least

physiologically well compensated before cardiac arrest

whereas hospitalized patients are heterogeneously ill

Nielsen N et al. Acta Anaesthesiol Scand 2009; 53: 926‐943Nunnally ME et al. CCM 2011; 29(5): 1113‐1125Wolff B et al. International Journal of Cardiology 2009; 133: 223–228

Time since ROSC

The relationship between the onset of hypothermia and the

resulting neuroprotection is unclear

Effect of Presenting Rhythm

TH and favorable outcome:Nonshockable rhythm

• Retrospective cohort study of patients with a witnessed out of hospital cardiac arrest with an initial rhythm of PEA or asystole

TH and unfavorable outcome:Shockable vs Nonshockable rhythm

Testori C et al. Resuscitation 2011; 82: 1162‐1167.Terman SW et al. CCM 2014; 42: 2225‐2234.

• Retrospective cohort study of patients with a witnessed out of hospital cardiac arrest treated with TH

Who

What

When

How

Why

Which of the following should be considered when selecting a

technique for cooling:

Speed of induction

Maintenance of a narrow temperature range

Ability to provide controlled rewarming

All of the above

Ideal Technique for Cooling

• Ideal technique:

• Rapid temperature reduction

• Cooling of target organs• Maintain temperature in a narrow range

• Controlled rewarming

• Easy transport and use during CPR• Easy to use during routine care



Temperature Management• Cold fluids (4ºC)

• 30‐40 mL/kg

• Limitations: poor for maintenance, overcooling, volume

• Ice packs and cooling blankets

• Advantages: low cost

• Limitations: low cooling rate, skin damage, temperature maintenance, nursing care

• Hydrogel‐coated cooling pads

• Advantages: temperature maintenance, use with routine care

• Limitations: high cost, skin complications (rare)

• Intravascular devicesSeder DB, et al. CCM 2009; 37(7): S211‐S222.

Temperature Induction & Maintenance

Hoedemaekers CW et al. Critical Care 2007; 11(4): 1‐9.

Overcooling

Temperature # ptsTotal n=32

< 32 C 20

< 31 C 9

< 30 C 4

• Survival to hospital discharge:

• 30 % temp < 32 C

• 58% temp > 32 C

• NS

Retrospective chart review at 3 large teaching hospitals

Target temperature 32‐34 CUtilized surface cooling techniques

Merchant RM et al. CCM 2006; 34 (12): S490

The target temperature for TH is well defined:

Yes

No

Retrospective chart review of 828 adult patients following a witnessed out of hospital cardiac arrest with a GCS < 8 at

admission. Evaluated the effects of spontaneuousnormothermia (< 37.5 C) comparded with mild TH.

Horburger D et al CCM 2012; 40: 2315‐2319.

Normothermia vs Hypothermia

International trial in 36 ICUs that randomly assigned 950 unconscious adult patients to a target temperature

of 33 C or 36 C following cardiac arrest

Outcome 33C group

36 C group

P value

≥ 1 serious ADE 93% 90% 0.09

Hypokalemia 19% 13% 0.02

Nielson N et al. NEJM 2013



Who

What

When

How

Why

Outcomes following cardiac arrest have improved over time:

True

False

Cardiac Arrest Outcomes

• Survival to hospital discharge has improved over time• For all rhythms

• 2000 13.7%• 2009 22.3%

• Rates of clinically significant neurologic disability (CPC score at discharge, >1) among survivors has decreased over time• For all rhythms

• 2000 32.9%• 2009 28.1%

• Early recognition, resuscitation, postresuscitation care

Girota S et al. N Engl J Med 2012;367:1912‐20.

Patient Case


What elements of this patient case make the application of TH

controversial?

Key Takeaways

• Key Takeaway #1

• Clinical Controversy regarding the application of TTM exists in multiple areas including who, what, when, how, and why

• Key Takeaway #2

• The strongest grade of recommendation is given for out‐of‐hospital adult cardiac arrest patients with a first registered rhythm of ventricular fibrillation or pulseless ventricular tachycardia who are unconscious after ROSC



Pharmacotherapy Considerations in Management of Therapeutic

Hypothermia: focus on shivering and glucose

Paul M. Szumita, PharmD, BCPSClinical Pharmacy Practice Manager

Director Critical Care Pharmacy Residency ProgramBrigham & Women’s Hospital, Boston, MA

Objective

• Breakdown and evaluate the pharmacotherapy considerations for patients requiring therapeutic hypothermia wit a focus on shivering management and glucose management

Complications of TH• Infection/pneumonia• bleeding• Acid/base• Shivering/not meeting target temperature• Electrolytes (Potassium, magnesium, phosphate)• Glucose management• Hemodynamics (Bradycardia and hypotension)• Mechanical ventilation• Pharmacokinetic alterations• Seizure and myoclonus

Empey PE, et al. Crit Care Med. 2013 Oct;41(10):2379‐87. Perbet, S, et al. Am J Respir Crit Care Med. Vol 184.2011: 1048–1054, 2011Geurts M, et al. Crit Care Med. 2014 Feb;42(2):231‐42. Mikkelsen M, et al. Crit Care Med. 2013 Jun;41(6):1385‐95.Noyes AM, Lundbye JB. J Intensive Care Med. 2013 Dec 25. [Epub ahead of print]

Yes

No

Not formalized

Not sure

Does your institution have a protocol for prevention, assessment and management of shivering?

Shivering• Involuntary oscillatory

skeletal muscle activity• Shivering “threshold” is ~1°C

below the vasoconstriction threshold

• Activates autonomic and hemodynamic responses

• Increases the resting energy expenditure and caloric consumption

• Typically happens in the induction phase

• Once in maintenance of TH shivering less frequently a complication

Seder DB, Van der Kloot TE. Crit Care Med . 2009; 37: S211‐22Badjatia N, Strongilis E, et al. Stroke 2008; 39: 3242‐4Logan A, et al. Crit Care Nurse. 2011 Dec;31(6):e18‐30.

Park SM, et al. Crit Care Med. 2012 Nov;40(11):3070‐82.

• Frequent assessment is key • Pharmacologic and non‐

pharmacologic strategies can be used to prevent and treat shivering

• Non‐pharm• Head and hand warming• Warming blankets

• Pharm: Neuromuscular blockers, opioids and sedative use and higher magnesium levels have been associated with significant reductions in shivering

Thermoregulatory Defenses

Sessler DI. CCM 2009; 37(7): S203‐S210

Threshold (Celsius)

38

37

36

35

Sweating Constriction Shivering

Men

Women



Induction

Phase

Maintenance

Phase

Rewarming

Phase

Maintenance of Normothermia

24 hrs

0 hrs 72 hrs

Shivering

Goal: To rewarm the patient in a slow and controlled fashion at 0.2 to 0.5 º Celsius per hour Risks associated with

speed of rewarming Maintain normothermia

with cooling pads for 48 hours after rewarming

TimelineShivering assessment

• Bedside Shivering Assessment Scale• 0 = none

• No shivering noted on palpitation of masseter, neck or chest wall

• 1 = Mild• Shivering localized to the neck and/or thorax only

• 2 = Moderate• Shivering involves gross movement of the upper extremities

• 3 = Severe • Shivering involves gross movement of the trunk and upper and lower extremities

Badjatia N, Strongilis E, et al. Stroke 2008; 39: 3242‐47

Propofol

Midazolam

Dexmedetomidine

Neuromuscular blocker with a sedative

Which primary agent is the primary sedative agent used to management of shivering at your institution?

Medication used to Manage Shivering

• Magnesium• Opioids

• Remifentanil• Meperidine• Fentanyl• Morphine

• Dexmedetomidine • Clonidine• Propofol• Neuromuscular blockers• Ketamine• Midazolam• buspirone

Bjelland T, et al. Intensive Care Med (2012) 38:959–967

Controversies and Questions

• What agent or combination of agents to has the best outcomes?

• Should all patients get NMB?

• How deep should we sedate the patients?

Light vs. Deep Sedation on clinical outcomes and mental health after critical illness

p = 0.03

p =0.47

p = 0.02

Significant patient characteristics/metrics/outcomes

Light Deep P value

PTSD score ICU discharge*

52 57 0.39

PTSD score 4wks post ICU*

46 56 0.07

*Data presented in mean †Data presented as n (%) of Event Scale-Revised PTSD

Single center, prospective, open label trial of 137 ICU patients requiring mechanical ventilation randomized to light (Ramsey 1‐2) or deep (Ramsey 3‐4) sedation at Geneva Hospital Switzerland. Extensive exclusion criteria, removing high risk patients and those with baseline cognitive dysfunction.

Treggiari MM, et al. Crit Care Med. 2009 Sep;37(9):2527‐34.



Moderate Level of Sedation/Analgesia May be Appropriate… however

• Moderate level of sedation/analgesia is possible with minimal need for NMB

• In healthy volunteers; cooling has been achieved in conscious patients

• However:

• Lower requirements for sedatives have been associated with worse outcomes in some studies

• May be a marker of poor neurologic outcomes (patients are worse off to begin with)

• NMB MAY be associated with better outcomes….May TL, et al. Neurocrit Care. 2014 Jun 25. [Epub ahead of print]

Testori C, et al. Crit Care. 2011;15(5):R248.Burjek, NE, et al. Crit Care Med. 2014 May;42(5):1204‐12

Salciccioli JD, et al. Resuscitation. 2013 Dec;84(12):1728‐33.

Neuromuscular blockers: to add or not?• Shivering is associated with better outcomes observationally• Shivering patients are more likely to receive NMB; therefore selection bias may explain

• Continuous or bolus?• Bolus was associated with:

• Quicker to target temp• Less total exposure to NMB• Equal time in TOF

• Many believe NMB should be used for breakthrough shivering only due to side effects of NMB

• Perhaps a X1 dose at induction (future study)Noyes AM, Lundbye JB. J Intensive Care Med. 2013 Dec 25. [Epub ahead of print}Jurado LV, et al. Pharmacotherapy. 2011 Dec;31(12):1250‐6. Noyes AM, Lundbye JB. J Intensive Care Med. 2013 Dec 25. [Epub ahead of print

Magnesium Therapy

• Reduces shivering thresholds

• Produces peripheral vasodilation and increases cooling rates

• Has antiarrhythmic properties

• Some animal data indicate added neuroprotection

Zweifler RM, Voorhees ME, et al. Stroke 2004; 35: 2331‐34

Patient Case

• AS 92 yo male suffering cardiac arrest at SNF due to respiratory failure. Patient was down for unknown period of time. Bystander CPR initiated, EMS arrived 4 minutes after call, presenting rhythm was asystole. Patient received 1 round of epinephrine and atropine and had ROSC 5 minutes after EMS arrival. Patient transferred to BWH ED, initial GCS 3 (no sedatives given), in sinus tachycardia.

• Pt on propofol and fentanyl infusion• 2 hours into cooing pt temp is 35 degrees with shivering score of 2

Increase Propofol and fentanyl infusions

bolus NMB

Start dexmedetomidine

Continuous NMB

For AS what would you do to treat the current shivering?

Example Prevention and Management of Shivering Strategy

• Prevention• Non‐pharmacologic

• Warm hand, head and heating blanket• Magnesium bolus 4‐6 grams X1 (run over 4 hours)• Low dose opioid and propofol infusions

• Frequent assessment with bedside shivering scale• Treatment of breakthrough

1. Simultaneous Bolus opioid and propofol drip titration Q 10 min X3

2. NMB bolus Q10 min X33. NMB infusion (refractory only)

• Turn off infusions during rewarming



Glucose During TH

• Hyperglycemia is associated with (observational) increase in poor outcomes

• Neurologic

• Mortality

• Hyperglycemia and hypoglycemia are common

• Hyperglycemia typically during cooling

• Hypoglycemia during rewarming

Daviaud F, et al. Intensive Care Med. 2014 Jun;40(6):855‐62. Kim SH, et al. Am J Emerg Med. 2014 Aug;32(8):900‐4 . Forni AA et al. Crit Care Med. Dec 20124(12):1‐328.

Same IV insulin protocol as other ICU patients

Same IV insulin protocols as other ICU patients with a few provisions

Different IV insulin protocol

Not sure

How does your institution manage hyperglycemia during Therapeutic Hypothermia?

Guidelines from Professional Organizations on ICU Blood Glucose (BG) Goal

Year Organization Patient Population

BG Treatment Threshold

(mg/dL)

BG Target

(mg/dL)

BG Hypoglycemia

Definition(mg/dL)

Updated since NICE-

SUGAR, 2009

2009 AACE and ADA ICU patients 180 140–180 <70 Yes

2013 Surviving Sepsis Campaign

ICU patients 180 <180 Not stated Yes

2009 Institute for Healthcare Improvement

ICU patients 180 <180 <40 Yes

2012American College of Critical Care Medicine (ACCM)

ICU 150

<150 (Trauma)

<180(Stroke+)

<70 Yes

2013 American College of Physicians ICU patient Not stated 140–200 Not stated Yes

2008 American Heart Association

ICU patients with ACS

180 90–140 Not stated No

Kavanagh BP et al. N Engl J Med. 2010; 363:2540-6.Qaseem A et al. Ann Intern Med. 2011; 154:260-7.

Jacobi J. Crit Care Med. 2012; 40:3251-76.Finfer S et al. N Engl J Med. 2009; 360:1283-97.

IV Insulin in the ICU Setting

Jacobi J. Crit Care Med. 2012; 40:3251‐76.Moghissi ES et al. Diabetes Care. 2009; 32:1119‐31.

Antihyperglycemic Therapy

InsulinRecommended

Oral Antidiabetic DrugsNot generally recommended

IV Insulin

Critically ill patients in the ICU

SC Insulin

Non‐critically ill patients

Ins, n 2 3 4 6 7 7 7 8 9 9 9 8 9 9 10 10 9 9 8 9 9 9 8 8 8 6 5 5 5 5 5 5 5 5 5 5 3

BG, n 2 5 7 7 6 7 9 7 10 10 9 9 9 9 11 10 10 8 11 10 10 11 9 11 9 9 10 11 8 7 7 7 7 7 5 5 4

Forni AA et al. Crit Care Med. 40(12):1‐328, December 2012

Managing Hyperglycemia during TH

• No consensus on “how to manage” hyperglycemia specifically related to TH

• Is the typical 180 mg/dL or below appropriate for these patients?

• Typically require high doses of insulin during cooling

• Insulin requirements lower during rewarming



Example Strategy for Managing Glucose during TH

• Initiate IV insulin when glucose is greater than 200mg/dl

• Do not exceed 50 units insulin / hour • Stop continuous intravenous insulin when glucose levels drop to less than 200 mg/dl, unless type 1 diabetes mellitus

• If patient has type 1 diabetes, continue IV insulin at a rate of 0.5 units/hour

• Check glucose every 30 minutes if glucose < 80 mg/dl until rewarming complete and glucose stabilized > 100 mg/dl

Potassium

• TH increases urine output (wasting of K) and pushes K into the cell during cooling

• Potassium replacement:

• Consider replete potassium to maintain levels >4.0 mEq/L

• Typically discontinue K+ repletion 4 hours prior to rewarming, unless K+ is less than 3.5

• Potassium levels may continue to be elevated hours past re‐warming and require continued frequent electrolyte monitoring

Alterations in Medication Pharmacokinetics

• Metabolism • Altered temperature= altered enzyme activity

• Conformational shape changes at receptor site

• Less activation or inactivation of drug and metabolite

• Prolongation of prodrug conversion to active drug

• Higher serum concentrations of active compounds which result in toxic effects

• Accumulation of metabolites

• Elimination• Biliary clearance

• Impaired hepatic blood flow

• Renal clearance

• Renal blood flow decreased

• Impaired CrCL during maintenance and effect reversed upon rewarming

• Increased UOP thought to be due

to impaired tubular secretion Tortorici MA, et al. CCM 2007; 35: 2196‐2204.

• Absorption • Slow rate of availability

• Onset delay

– Prolongation of time to Cmax

• Reduction in gastric motility causes variability with oral dosage formulations

• Distribution• Vd dependent upon:

– Blood flow redistribution

– Blood pH increases and pCO2 decreases

• Drugs with pKa of 7‐8 are most affected during IH

– Alterations in protein binding

– Lipid solubility

– Tissue binding capacityArpino PA and Greer DM. Pharmacotherapy 2008; 28(1): 102‐111.

Empey PE, et al. Crit Care Med. 2013 Oct;41(10):2379‐87.

Example ‐ Patient Monitoring Guideline

• Seizure v myoclonus• EEG (goal less than 18

hours from admission)

• BIS in the rare case of NMB• Not reliable for sedative

drip titration

• TOF in the rare case of NMB• Baseline• Continue sedation until a

4/4 TOF is achieved

• RASS• Goal RASS ‐4 to ‐5 prior to

cooling

• Temperature• 2 methods of

measurement

• Shivering assessment scales

• Electrolytes, glucose, coagmonitoring

• Hemodynamic• Heart rate (bradycardia

common)• If clinical bradycardia, can warm to 93‐95 to see clinical effect

• MAP (goal > 90)• CVP (goal greater than 8

typically)

Badjatia N,et al. Stroke 2008;39:3242‐3247.

Quality Metrics ‐ Example

Times Minutes Goal

Downtime <15 min

ROSC to TH initiation <60 min

ROSC to ICU

ROSC to target temperature <300 min

ED to ICU time

TH initiation to target temperature <240 min

ICU to target temperature <180 min

Arctic Sun to target temperature <180 min

ICU to EEG <18 hours

Hypoglycemia occur? None

Breakthrough shivering meds given? List meds

Therapeutic hypothermia after cardiac arrest guideline Core

Management

• Patient selection• Cooling and rewarming process• Shivering• Electrolyte repletion• Hemodynamics and ventilation• Glucose management• Seizure and myoclonus• Prognosis



Key Takeaways• Key Takeaway #1

• Shivering is common complication leading to delays to target temperature. Prevention, regular assessment and management strategies are imperative.

• Key Takeaway #2

• Hyper and hypoglycemia are common during and cooling, maintenance and rewarding and are associated with poor outcomes.

QUESTIONS?



Documents

259-L01 Therapeutic Hypothermia Post Cardiac Arrest · 2014. 12. 2. · hypothermia post cardiac arrest. • Learning Objectives 2: Breakdown and evaluate the pharmacotherapy considerations