Induced Therapeutic Hypothermia

Aka: Induced Therapeutic Hypothermia, Therapeutic Hypothermia, Targeted Temperature Management

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II. Indications: Post-Cardiac Arrest Care

  1. Class I indications (AHA)
    1. Comatose patients (GCS<8) with STEMI
    2. Comatose patients with ROSC after witnessed Cardiac Arrest from Ventricular Fibrillation, pulseless VT
  2. Class 2B Indications
    1. Comatose patients (GCS<8) with ROSC after witnessed Cardiac Arrest from nonshockable rhythm
  3. No guidelines outside of non-pregnant adults
    1. Case reports only to date for induced Hypothermia for post-arrest pregnant women
    2. Children appear to benefit in post-arrest with Ventricular Fibrillation or Ventricular Tachycardia
      1. Good expert opinion support for induced Hypothermia in this cohort
    3. Newborns with hypoxic-ischemic encephalopathy
      1. Consider Sarnat Criteria to aid decision to start induced Hypothermia
  4. Unclear efficacy
    1. Subarachnoid Hemorrhage as a cause of Cardiac Arrest
      1. Induced Hypothermia is neuroprotective and may decrease Intracranial Pressure
      2. Efficacy similar to Hypertonic Saline or Mannitol
      3. Increased bleeding risk is minimized if core Temperature goal adjusted to 35 C (95 F)

III. Contraindications

  1. Comatose before Cardiac Arrest
  2. Multiple Traumatic injuries (Risk of bleeding)
  3. Intracranial Hemorrhage
  4. Exsanguination, Coagulopathy or recent major surgery with significant bleeding risk
  5. Hypotension requiring multiple Vasopressors
  6. Hemodynamically unstable (e.g. MAP <60 mmHg for >30 min)
  7. Severe Sepsis
  8. Acute Respiratory Distress Syndrome (ARDS)
  9. Significant QT Prolongation (QTc >550 ms)
  10. Initial core Temperature <30 C

IV. Mechanisms

  1. Cardioprotective
    1. Decreased Myocardial Infarction size
    2. Decreased myocardial metabolic demands
  2. Neuroprotective
    1. Decreased cerebral metabolism and neuroexcitatory mediators
    2. Improved Glucose Metabolism
    3. Decreased Oxygen Consumption (decreases 8% for every 1 C cooled)
    4. Inhibits inflammatory cascade (decreased free radicals, pro-inflammatory Cytokines)
    5. Decreased brain edema and Seizure risk

V. Precautions

  1. No evidence-based standardized guidelines for cooling protocol
  2. Start protocol as early as possible following Return of Spontaneous Circulation (ROSC)
    1. In one study, every hour of delay in starting Hypothermia protocol was associated with a 20% increase in mortality
    2. Mooney (2011) Circulation 124(2): 206-14 [PubMed]
  3. Transfer post-arrest patients to larger tertiary centers
    1. Initiate external cooling prior to transfer
    2. Best maintenance of core Temperature target, even when target is near normal at 36 C
    3. Larger centers have available equipment, practiced protocols to maintain consistent Temperature
    4. Post-arrest care is complex, multidisciplinary and an intensive use of resources

VI. Protocol: Cooling Initiation and Maintenance

  1. Onset and duration
    1. Start immediately following ROSC (preferably within 4 hours, at minimum within 6-8 hours of arrest)
    2. Pre-hospital cooling has not been shown to be beneficial
      1. Kim (2013) JAMA 311(1): 45-52 [PubMed]
    3. Typically goal Temperature achieved within 1-2 hours
    4. Continue for at least 12-14 hours (typically 24-48 hours in most protocols)
  2. Cooling techniques
    1. Cooled saline at 4 C (40 F) at 30 cc/kg over 30 minutes (2 Liters in a 70 kg adult)
      1. Drops Body Temperature 1-2 degrees/hour
      2. Continue cooled saline at maintenance until at hypothermic target
      3. Measured core Temperature lags actual by 20 minutes (caution at Temperature<35 C)
    2. Ice bags applied to bilateral side of neck, with bilateral axilla and groin
    3. Noninvasive methods are as effective as endovascular catheters initially
      1. However may require invasive cooling to maintain Hypothermia
      2. Transfer to a facility specializing in post-arrest care
  3. Goal core Temperature
    1. Non-trauama: 32 to 34º Celsius (89.6 to 93º F)
      1. Temperature of 32-33º C is preferred in non-Trauma patients
      2. Do not cool a patient to <32 C due to Arrhythmia risk
    2. Non-Trauma proposed new target: 36 C (experimental)
      1. Large study demonstrated no difference between 36 C and 33 C outcomes
      2. Target of 36 C may be preferred as easier to maintain than 33 C and less hemodynamic instability
      3. Orman and Weingart in Herbert (2014) EM:Rap 14(4):7-8
      4. Nielsen (2013) N Engl J Med 369(23): 2197-206 [PubMed]
    3. Trauma: 35 C (95 F)
      1. Do not drop Temperature below 35 C in Trauma patients (due to bleeding risk)
    4. Subarachnoid Hemorrhage: 35 C (95 F)
      1. Goal per neurosurgery recommendation
      2. Re-target core Temperature if cooled below 35 C (95 F) prior to Subarachnoid Hemorrhage diagnosis
        1. Avoid rapid transition to warmer core Temperature
        2. Allow core Temperature to rise 0.25 degrees per hour until 35 C (95 F)
  4. Prevent shivering (increases Body Temperature)
    1. Requires paralysis, sedation and Opioid Analgesics to prevent shivering
    2. Increase sedation (Propofol, Midazolam)
    3. Add Dexmedetomidine
    4. Consider Opioids
    5. Consider Magnesium 4 gram bolus (increases the shivering threshold)
  5. Monitoring
    1. Temperature monitoring (every 15 min)
      1. Pre-transfer to post-arrest unit
        1. Intermittent rectal probe
      2. Post-arrest ICU care (or if transfer is delayed for hours)
        1. Esophageal or Bladder probe (far preferred over rectal probe)
        2. Esophageal Temperature probes are inserted in similar fashion to Nasogastric Tube
          1. Positioning of probe is 2-3 inches above the xiphoid process
    2. Monitor Electrolytes and coagulation tests every 3-4 hours
      1. Anticipate significant diuresis with induced Hypothermia
      2. Risk of Hypovolemia and Electrolyte disturbance
      3. Labs at 4 hours after cooling started and then every 4 hours
        1. Serum Potassium (goal >4.0)
        2. Serum Magnesium
        3. Serum Phosphorus
        4. Blood Glucose 140-180 mg/dl
        5. Venous Blood Gas or Arterial Blood Gas
        6. Other periodic labs (CBC with Platelets, PT/INR, PTT)
    3. Monitor for Arrhythmia
      1. Avoid causes of Prolonged QT Interval due to Medication
      2. Expect Sinus Bradycardia
    4. Blood Pressure
      1. Arterial Line monitoring is preferred (typically initiated at tertiary, post-arrest center)
      2. Target mean arterial pressure >65 mmHg (and ideally >80 mmHg), and SBP >90 mmHg
    5. Ventilation
      1. Maintain a normal pH and pCO2 (40-45 mmHg)
      2. Maintain Oxygen Saturation >94%
    6. Other measures
      1. Routine skin care

VII. Protocol: Decooling

  1. Decool at 0.25 C per hour until core Temperature >37 C (typically over 12 or more hours)
  2. Replace fluids and Electrolytes as needed
  3. Discontinue paralytic and wean sedation as able
  4. Extubate when able
  5. Maintain MAP >65 mmHg (and ideally >80 mmHg), and SBP >90 mmHg
  6. Avoid hyperthermia

VIII. Efficacy

  1. Targeted Temperature Management (prevent hyperthermia or fever) is key
    1. Aggressive Hypothermia to <33 C does not have better outcomes than 36 C
    2. Protective effects appear more related to the prevention of fever or hyperthermia
    3. Neilson (2013) N Engl J Med 369: 2197-2206 [PubMed]
  2. Children: No signficant favorable data to support Therapeutic Hypothermia over preventing fever
    1. Reasonable to treat adolescents as adults
    2. Most important to prevent fever in the first 4-5 days (targeted temp between 36 to 37.5 C)
    3. Moler (2015) N Engl J Med 372(20): 1898-908 +PMID: 25913022 [PubMed]
    4. Change (2016) Resuscitation 105:8-15 +PMID:27185217 [PubMed]
  3. Number Needed to Treat following VFib or pulseless VT arrest: 6
  4. Improved neurologic outcomes following Ventricular FibrillationCardiac Arrest
    1. (2002) N Engl J Med 346(8):549-56 [PubMed]
    2. Bernard (2002) N Engl J Med 346(8): 557-63 [PubMed]
  5. Limited observational studies to date demonstrate no benefit in Cardiac Arrest non-shockable rhythm (PEA, Asystole)
    1. Dumas (2011) Circulation 123(8): 877-886 [PubMed]

IX. Adverse Effects: Hypothermia related

  1. Shivering (see above)
  2. Frostbite
  3. Hypoglycemia
  4. Renal effects
    1. Serum Potassium abnormalities
    2. Cold diuresis
  5. Bleeding
    1. Impaired Platelet function and Clotting Factor function
    2. Bleeding risk in Trauma at core Temperature <35 C (95 F) and especially <32 C (89.6 F)
  6. Slower hepatic metabolism
    1. Consider altering drug doses and frequency
  7. Theoretical effects (but has not been shown to have Clinically Significant effects)
    1. Bradycardia, decreased Cardiac Output and increased Systemic Vascular Resistance
    2. Decreased cellular and Humoral Immunity
  8. Other effects
    1. Altered Drug Metabolism

X. References

  1. (2016) CALS Manual, 14th Ed., 1:37
  2. Mattu in Herbert (2013) EM:Rap 13(8): 1-2
  3. Stefanos and Swaminathan in Herbert (2016) EM:Rap 16(11):17-8
  4. Winters et al in Herbert (2013) EM:Rap 13(7): 9-10
  5. Weingart and Orman in Herbert (2014) EM:Rap 14(1): 9-10
  6. Seder (2009) Crit Care Med 37: S211-22 [PubMed]

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