Hypothermia after Cardiac Arrest Protocol
Reviewed by the Critical Care Committee 2015
Patient Selection:
1. Those post out-of-hospital cardiac arrest with documented original rhythms
ventricular tachycardia or ventricular fibrillation.
[Induced hypothermia after PEA, asystolic, or in-hospital arrest has not been fully
studied, but may be applied at the discretion of the treating physicians].
2.
Those with return of spontaneous circulation within 60 minutes of arrest.
3. Those in coma at the time of cooling.
[Coma is defined as: Glascow Coma Scale less than or equal to 8 ].
Absolute Exclusion Criteria:
1. Preexisting code status of DO NOT RESUSCITATE and/or DO NOT INTUBATE.
2. Pregnancy
[Negative urine HCG is required prior to initiation of protocol on female patients
younger than 55 years old]
3. Sustained hypotension
[Defined as: SBP < 80 mmHg or MAP < 50 mmHg for greater than 30 minutes
despite vasopressor support]
4. Patients with known CNS hemorrhage.
[CT scan must be performed on arrival to rule out intracerebral hemorrhage]
5. Absolute body temperature of less than 30 C / 86 F.
Relative Exclusion Criteria:
1. For patients < 17 years of age, pediatric telephone consult recommended.
2. Greater than 6 hours after cardiac arrest.
3. Systemic infection/sepsis.
1/8/2008
4. Clinical suspicion of head trauma.
[CT scan must be performed on arrival to rule out intracerebral hemorrhage]
11
5. Patients with a known bleeding diathesis, or with active ongoing bleeding.
[Check PT/PTT, fibrinogen, D-dimer at admission. Note – patients may receive
chemical thrombolysis, antiplatelet agents, or anticoagulants if deemed
necessary in the treatment of the primary cardiac condition]
6. For patients being treated with warfarin (Coumadin) – consider reversal.
7. No existing multi-organ dysfunction syndrome, severe sepsis, or comorbidities
with minimal chance of meaningful survival independent of neurological status.
8. Drug intoxication known to cause CNS depression (i.e. opiates,
benzodiazepines, lithium, anti-epileptics, etc.).
Goal
If criteria are met, the patient is cooled using the induced hypothermia protocol for 24
hours at goal temperature of 33° Celsius (91.4° F). The target time to reach the
temperature goal is 6-8 hours. The 24 hour time period is from the time of initiation of
cooling (i.e. NOT the time the target temperature is reached).
Background
Approximately 80% of cardiac arrest survivors remain in a coma. Of those who awaken,
full neurological recovery is rare. Under ideal temperature and health conditions, the
oxygen available to the brain is depleted within 20 seconds once blood flow is
interrupted. Oxygen depletion leads to depletion of ATP and glucose stores within 5
minutes. Anaerobic metabolism leads to the buildup of lactic acid. Furthermore, ATP is
used to maintain membrane stability. Loss of ATP leads to ion equilibration between the
extracellular and intracellular environments within 10 minutes. Fluxes in calcium are
known to cause the release and activation of a large number of damaging enzymes and
neurotransmitters.
If perfusion and oxygenation are restored within 20 minutes, membrane stability and ion
gradients are quickly restored. (Of note, CNS ischemia of greater than 1 hour is
considered irreversible.) Leukotriene levels, however, remain elevated for up to 24 hours
after reperfusion, partly explaining the 20% - 40% of normal perfusion seen after
ischemia. Within 30 seconds of reperfusion, oxygen free radicals are released and
begin interacting with lipids and macromolecules, causing the greatest amount of
neuronal damage.
Under normal circumstances, the brain is highly dependent on protein synthesis and
turnover. Immediately after an ischemic insult, during a time of high metabolic need,
protein synthesis is suppressed and remains suppressed, leading to apoptosis.
Two cardinal studies were published in the New England Journal of Medicine in 2002
demonstrating the effects of mild induced hypothermia (MIH) as a neuroprotective
treatment modality following cardiac arrest. The first study, a four-centered Australian
21
prospective controlled trial, included 77 patients with out-of-hospital cardiac arrest. This
study cooled patients pre-hospital to a goal core temperature of 33 degrees within 2
hours after return of circulation and maintained this for 12 hours. Primary end point was
good cerebral function at discharge based on ability to be discharged to home or
rehabilitation center. The second study, a randomized control trial conducted at nine
centers in five European countries, included 273 patients with witnessed in-hospital
(N=10) or out-of-hospital cardiac arrest. This study cooled patients to 32-34 degrees
Celsius over 24 hours. The primary end point was good cerebral function six months
after cardiac arrest (defined as either normal cerebral function or adequate function to
live independently and work part-time). Secondary end points were complications within
seven days of cardiac arrest or death within six months after cardiac arrest.
Bernard SA, Gray TW, Buist MD et al. Treatment of comatose survivors of out-ofhospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346: 557–
63.
The Hypothermia after Cardiac Arrest (HACA) study group. Mild therapeutic
hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J
Med 2002; 346: 549–56.
Summary of results:
Hypothermia Normothermia
p value
Favorable neurological outcome
Bernard et al.
49% (21/43) 26% (9/34)
0.046
HACA Study Group
55% (75/136) 39% (54/137)
0.009
(n=273, normal to adequate cerebral function allowing patient to live independently and
to work, at least, part-time)
Mortality
Bernard et al.
51% (22/43) 68% (23/34)
RR 0.76; NNT=6
HACA Study Group
41% (56/137) 55% (56/138) RR 0.74; p=0.02
Adverse Events
Bernard et al
No difference in adverse events
HACA Study Group
No significant difference, but 22% more overall
More PNA with NNH=12, bleeding NNH=14, Sepsis NNH=16
It is known that hypothermia decreases oxygen demand and cellular metabolism – two
processes leading to neuronal destruction during and after ischemic insult. The studies
listed above demonstrate that hypothermia decreases the chance of death and
increases the chance of neurological recovery after resuscitation from cardiac arrest.
These studies prompted the publication of recommendations by the International Liaison
Committee on Resuscitation (ILCOR) in 2003 for the therapeutic application of MIH in
unconscious adult patients with spontaneous circulation after out-of-hospital cardiac
arrest. A review of the evidence resulted in Level 1 recommendations for hypothermia
in Ventricular Fibrillation and prompted clinicians to consider other primary rhythms that
lead to arrest.
Nolan JP, Morley PT, Vanden Hoek TL, Hickey RW. Therapeutic hypothermia
after cardiac arrest. An advisory statement by the advanced life support task
force of the international liaison committee on resuscitation. Circulation 2003;
108: 118–21.
31
Earlier research conducted in the field that also lends support to the effectiveness of
induced hypothermia in comatose survivors of cardiopulmonary arrest:
Bernard SA, et al. Clinical trial of induced hypothermia in comatose survivors of out-ofhospital cardiac arrest. Ann Emerg Med 1997;30:146-53
YanagawaY, et al. Preliminary clinical outcome study of mild resuscitative hypothermia
after out-of-hospital cardiopulmonary arrest. Resuscitation.1998;39:61-6
Nagao, et al. Cardiopulmonary cerebral resuscitation using emergency cardiopulmonary
bypass, coronary reperfusion therapy, and mild hypothermia in patients with cardiac
arrest outside the hospital. J Am Coll Cardiol. 2000;36;776-83
Zeiner A. Mild resuscitative hypothermia to improve neurologic outcome after cardiac
arrest: a clinical feasibility trial. Stroke. 2000; 31:86-94
41
Complications associated with hypothermia/rewarming
Hypothermia is associated with shivering, decrease in oxygen delivery, tachycardia
which progresses to bradycardia, arrhythmias, coagulopathy, diuresis, electrolyte
imbalances, hypoglycemia secondary to decreased insulin secretion, metabolic acidosis,
lactic acidosis, and increased amylase. The maintenance phase of the hypothermia
guideline is designed to address many of these issues.
Rewarming is associated with: hypotension, decrease in CVP, and hyperkalemia.
Before rewarming begins, the patient should be fully fluid resuscitated.
Potassium should be followed every 4 hours and ACP checked every 1 hour and
as needed.
51
The following are suggested guidelines based on published data described in the
preceding pages for the use of mild induced hypothermia in post ventricular
tachycardia/ventricular fibrillation cardiac arrest patients. Any use of these guidelines
that do not meet the inclusion and exclusion criteria as presented below is done at the
discretion of the attending of record.
Protocol
Patient selection:
 Resuscitated post out-of-hospital VF or VT cardiac arrest
[Use of MIH for in-hospital cardiac arrest or non-VT/VF cardiac arrest has not
been adequately studied, however, implementation of this protocol in such cases
is at the discretion of the attending of record. Please document rhythm and
location of patient at time of arrest.]
Document rhythm
_________
Location at time of arrest
_________
 Return of spontaneous circulation < 60 minutes after arrest
Time from arrest to ROSC _________
 Coma
Glascow Coma Scale  8
_________
Glascow Coma Scale
Eye Opening:
Spontaneous with blinking
Opening to verbal stimuli
To pain only
No response
4
3
2
1
Motor response:
Moves to command
Moves purposefully to pain
Withdraws from pain
Flexion to pain
Extension to pain
No response
6
5
4
3
2
1
Verbal Response:
Oriented
Confused but answering questions
Inappropriate words
Incomprehensible speech
No Speech
5
4
3
2
1
Absolute exclusions:
 Preexisting code status DO NOT RESUSCITATE and/or DO NOT INTUBATE
 Pregnant
Urine HCG results
_________
 Sustained hypotension (SBP < 80 mmHg or MAP < 50 mmHg)  30 minutes
despite vasopressor support)
 Absolute body temperature < 30 C / 86 F
 Known CNS hemorrhage
CT scan results
_________
61
Relative exclusions:
 Patients < 17 years of age, pediatric telephone consult with Children’s Hospital
pediatrician on-call recommended
 Greater than 6 hours after cardiac arrest
 Systemic infection/sepsis
 Clinical suspicion of head trauma
 Patients with a known bleeding diathesis, or with active ongoing bleeding
 Patients being treated with warfarin (Coumadin) – consider reversal
 No existing multi-organ dysfunction syndrome, severe sepsis, or comorbidities
with minimal chance of meaningful survival independent of neurological status
 Drug intoxication known to cause CNS depression (i.e. opiates,
benzodiazepines, lithium, anti-epileptics, etc.)
71
Initiation of the Protocol:
Procedures and Labs on arrival: Time _________
 Urine HCG
 CBC
 *Acute Care Profile  PT/INR and PTT
 Mg
 Phos
 Lactate
 Cardiac Enzymes
 Cortisol
 Blood Cultures
 Urine Culture
 Sputum Culture
*Exact temperature must be recorded on the label and when ordering every ACP as
results are adjusted significantly in the laboratory for temperature
 ECG
 Place arterial line
 CT scan to rule out CNS hemorrhage
 Record temperature Q60 minutes on Critical Care flowsheet using 2 of the
following methods: (please indicate which methods are being used)
 Foley temperature probe
 Rectal probe
 Tympanic temperature probe
 Pulmonary Artery Catheter temperature probe
 Other
 Goal MAP > 90 mmHg (preferably) using IVF and vasopressors if needed
 Insulin protocol for goal serum glucose < 150 mg/dL
81
Patient Comfort:
Pain
 Fentanyl
 Loading dose: ________mcg IVP (suggested 50 – 100 mcg)
 Continuous gtt: ________mcg/hr (FRACC Pain Score goal = 0)
 Morphine
 Start at ________ mg/hr (titrate to FRACC Pain Score goal = 0)
Sedation
RASS goal of “Deep Sedation” -4
RASS: Richmond Agitation Sedation Score
+4
Combative
Combative, violent, immediate danger to staff
+3
Very Agitated
Pulls or removes tubes or catheters, aggressive
+2
Agitated
Frequent nonpurposeful movements, fights ventilator
+1
Restless
Anxious, apprehensive, movements not aggressive or vigorous
0
Alert and Calm
-1
Drowsy
Not fully alert but has sustained awakening to voice
-2
-3
-4
Light Sedation
Moderate Sedation
Deep Sedation
-5
Unarousable
Briefly awakens to voice ( 10 seconds)
Movement or eye opening to voice (no eye contact)
No response to voice; movement or eye opening to
physical stimulation
No response to voice or physical stimulation
 Propofol (avoid if hypotensive)
 Start at 5 mcg/kg/hr then titrate to RASS -4 (max 80 mcg/kg/hr)
 Midazolam
 Loading dose: _________ mg IVP (suggest 2 – 6 mg IV push)
 Continuous gtt: _________ mg/hr titrate to RASS –4 (max 8mg/hr)
 Lorazepam
 Loading dose: _________mg IVP (suggest 2 – 6 mg IV push)
 Continuous gtt: _________mg /hr titrate to RASS –4 (max 8mg/hr)
 Dexmedetomidine
 Loading dose: ____________(suggest 1 mcg/kg over 10 minutes)
Note: The loading dose may be omitted if patient is either being converted from
another sedative and/or patient is adequately sedated or there are concerns for
hemodynamic compromise.

Continuous gtt: ____________ (dose range 0.2 to 1.5 mcg/kg/hour;
titrate every 30 minutes)
91
Shivering
Shivering can occur during active cooling, warming or throughout the period of
“Therapeutic Temperature Management”.
 Shivering can cause a dramatic increase in myocardial oxygen demand (as high
as 200 – 400 %)
 Shivering and fever both cause significant increases in cerebral oxygen demand
and consumption and may increase ischemia to the penumbra.
 Shivering must be aggressively treated if present.
Monitoring:
Utilize the Bedside Shiver Assessment Scale (BSAS).
Assessed and documented hourly.
Assess for shivering in the masseter muscles initially. To assess, rest finger
tips of both hands along the ridge of the mandible. A humming will be felt.
Bedside Shivering Assessment Scale (BSAS)
Score Shivering Status
Description
Action
0
None
No Shivering
None needed
1
Mild
Shivering localized to the neck/thorax only,
Monitor closely, initiate
palpable mandible vibration, or artifact on ECG counter-warming
measures (step 1)
2
Moderate
Intermittent involvement of the upper
Escalate anti-shivering
extremities, +/- thorax
interventions to maintain
BSAS ≤ 1 (step 2)
3
Severe
Generalized shivering, involves gross
Bolus sedation and
movements of the trunk and upper and lower
escalate anti-shivering
extremities
interventions to maintain
BSAS ≤ 1 (step 2 and 3)
Step 1: Counter Warming Measures
 Counter-Warming Methods:
 Place socks on the patient’s hands and feet
 Apply Bair Hugger to patient, cover arms, legs, hands, feet
 Set Temperature to HIGH
 Cover head with a hat or blanket
 Warm Face - tent
Step 2: Pharmacologic Agents
 Acetaminophen 650 mg every 4 hours PR or NG
 Magnesium 2 gm IV every 3 hours prn if Magnesium < 1.8 OR
 Magnesium infusion 0.5 – 1 gm/hour (if serum level < 1.8)
 Demerol 25 mg IV Q4H PRN shivering
(check creatinine clearance)
 Sedation bolus and/or infusion titration as ordered
101
Step 3: Paralysis
Paralysis
Prior to the use of any paralytic agent, the patient’s pain must be well controlled
and adequate sedation must have been achieved.
DO NOT PARALYZE A PATIENT WHO IS NOT ADEQUATELY
SEDATED
Once sedation has been achieved, initiate train of four (TOF).
There are numerous techniques that are designed to test the depth of
neuromuscular blockade using peripheral nerve stimulation; however,
the TOF approach is considered to be the easiest and most reliable
method for the ICU setting.1 Four equal electrical charges are delivered
every 0.5 s from the nerve stimulator device that is attached to leads
overlying a superficial nerve, usually the ulnar or facial nerve, and the
contraction of the innervated muscle (ie, the adductor pollicis or
obicularis occuli muscle, respectively) is graded subjectively by
palpation or observation. Guidelines1 support the titration of NMBAs, so
that one to two of four twitches are present when the nerve is
stimulated. No twitches would indicate a deep paralytic state and 4
would indicate a light paralytic state.
[1
Murray, MJ, Cowen, J, DeBlock, H, et al (2002) Clinical practice
guidelines for sustained neuromuscular blockade in the adult critically ill
patient. Crit Care Med 30,142-156]
 Vecuronium
 Loading dose: 0.05 – 0.1 mg/kg (goal TOF 1 of 4)
 Maintenance dose: 0.8 – 1.7 mcg/kg/minute
 Nimbex (Cisatracurium)
Note: Recommended for patients with liver and renal impairment


Loading dose: 0.15 to 0.2 mg/kg IV bolus (goal TOF 1 of 4)
Maintenance dose: 1 to 3 mcg/kg/min
 Train of Four initiated at start of infusion.
 Train of Four to be assessed and documented every four hours and with
rate changes of the paralytic infusion.
Mark electrode placement for ongoing assessment. Monitor paralysis
using Train of Four with goal therapy 1 of 4.
 At 33 C (91.4 F), turn paralytic OFF for one hour and re-assess need. If
not shivering, leave the paralytic off
111
Cooling:
Note: Avoid bathing during hypothermia portion of the protocol.
 Arctic Sun
[Cannot be used for patients with BSA >2.4 m2. If BSA >2.4 m2, then use
cooling blankets and ice packs as described below.]





NO Potassium replacements 8 hours before initiation of rewarming
Place cooling pads around patient’s torso and legs.
[For patients weighing 45 – 100 kg (100 – 220 lbs) use a standard
pad kit consisting of 4 pads. For patients weighing >100 kg, use 1
or 2 additional pads.]
Set cooling device to AUTOMATIC MODE.
Begin cooling to goal temperature of 33C (91.4F) to be reached
as quickly as possible.
Begin rewarming 24 hours after the initiation of cooling.
 Manual Cooling Method
 Place 2 cooling blankets on patient. One under patient and one on
top of patient. The cooling blankets should have sheets between
them and the patient. Cooling blankets should NOT have direct
contact with patient’s skin.
 Place ice packs in the following areas: groin, axilla, around chest
(not on chest), and sides of neck.
 Goal temperature is 33C (91.4F).
 Once temperature reaches 34C (93.2F), remove ice packs to
prevent over shooting the goal temperature. Maintain goal
temperature using cooling blankets. Ice packs may be replaced as
needed.
 Begin rewarming 24 hours after the initiation of cooling.
121
Procedures and Labs at 6 hours after initiation of cooling: Time _________
 CBC
 Phos
 PT/INR and PTT
 *ACP
 Cardiac Enzymes
 Mg
 Lactate
*Exact temperature must be recorded on the label and when ordering every ACP as
results are adjusted significantly in the laboratory for temperature
 Lacralube to eyes
 Skin care – check for burns caused by cooling apparatus
Procedures and Labs at 12 hours after initiation of cooling: Time _________
 CBC
 Phos
 PT/INR and PTT
 ACP
 Cardiac Enzymes
 Mg
 Lactate
 Blood Cultures
*Exact temperature must be recorded on the label and when ordering every ACP as
results are adjusted significantly in the laboratory for temperature
 ECG
 Skin care – check for burns caused by cooling apparatus
Procedures at 16 hours after initiation of cooling:
 Stop all potassium containing medications and/or infusions
Time _________
Procedures and Labs at 18 hours after initiation of cooling: Time _________
 CBC
 Phos
 PT/INR and PTT
 ACP
 Cardiac Enzymes
 Mg
 Lactate
*Exact temperature must be recorded on the label and when ordering every ACP as
results are adjusted significantly in the laboratory for temperature
 Skin care – check for burns caused by cooling apparatus
Procedures and Labs at 24 hours after initiation of cooling: Time _________
 CBC
 Phos
 PT/INR and PTT
 ACP
 Cardiac Enzymes
 Mg
 Lactate
*Exact temperature must be recorded on the label and when ordering every ACP as
results are adjusted significantly in the laboratory for temperature
 Skin care – check for burns caused by cooling apparatus
131
Re-Warming:
Stop all potassium containing medications/infusions 8 hours before initiation of
rewarming.
Re-warming at 24 hours after initiation of cooling: Time_________
 Controlled rewarming with the Arctic Sun
 Begin re-warming at a maximum rate of 0.25ºC per hour (0.45ºF per hour)
or 1.0C over 4 hours.
 Set goal temperature to 37C (98.6F) and program machine to maintain
this temperature for 48 hours.

Discontinue paralytic agents at core temperature of 36C (96.8F).
Paralytics should be discontinued BEFORE sedatives.
 Titrate sedative agents down to comfort/vent compliance once a TOF 4/4
is reached.
 Passive rewarming
 Begin passive re-warming at a maximum rate of 0.25ºC per hour (0.45ºF
per hour) or 1.0C over 4 hours.
 Do not exceed this rate as the potential for significant complications
(arrhythmias, status epilepticus and rebound hyperthermia) increases.
 Goal temperature is 36C (96.8F). Temperatures above 37C (98.6F)
should not be tolerated. Use acetaminophen 650 mg PO Q6 hours for
temperature >36.5C. If unable to maintain temperature <36.5C, use
cooling blankets as well.
 Discontinue paralytic agents at core temperature of 36C (96.8F).
Paralytics should be discontinued BEFORE sedatives.
 Titrate sedative agents down to comfort/vent compliance once a TOF 4/4
is reached.
Procedures and Labs:
1 hour after initiation of re-warming:
Time ________
 *ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
*Exact temperature must be recorded on the label and when ordering every ACP as
results are adjusted significantly in the laboratory for temperature
 Shivering Assessment using BSAS
2 hours after initiation of re-warming:
Time ________
 * ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
141
3 hours after initiation of re-warming:
Time ________
 * ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
4 hours after initiation of re-warming:
Time ________
 Potassium
 * ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
5 hours after initiation of re-warming:
Time ________
 * ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
6 hours after initiation of re-warming:
Time ________
 * ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
7 hours after initiation of re-warming:
Time ________
 * ACP  Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
8 hours after initiation of re-warming:
Time ________
 * ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
9 – 14 hours after initiation of re-warming:
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS every hour until target temperature of 37 º C
(98.6 º F) is reached
14 hours after initiation of re-warming:
Time ________
 * ACP
 Vital Signs (heart rate, blood pressure, temperature, O2 sat)
 Shivering Assessment using BSAS
151
Normo-thermia Maintenance
 Maintain a target temperature of 37 º C (98.6 º F) for the next 48 hours.
Fever Management:
1. Routine treatments for fever have been implemented:
 Tylenol
 Ibuprohpen
 Regular cooling blanket or cool packs to axilla and groin
 The patient has been fully cultured prior to initiation of cooling.
2. If above measures are not effective:
 Set Arctic Sun to a goal temperature of 37 C (98.6 F)
161
Appendex 1:
Hypothermia Re-Warming Guide
*Re-warm at 0.45 degrees Fahrenheit per hour
Approximate re-warming time is 16 hours
Hour
Time
Actual Temp
Goal Temp
Start time:
91.4
Hour 1
91.8
Hour 2
92.3
Hour 3
92.7
Hour 4
93.2
Hour 5
93.6
Hour 6
94.1
Hour 7
94.5
Hour 8
95.0
Hour 9
95.4
Hour 10
95.9
Hour 11
96.3
Hour 12
Hour 13
96.8
(Paralytic Off)
97.2
Hour 14
97.7
Hour 15
98.1
Hour 16
98.6
Water Temp
171