Therapeutic hypothermia

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Background

  • Determination of Neurologic Prognosis is unreliable before at least 72 hours after ROSC
    • Do not neuroprognosticate until 72 hours post rewarming.
  • Greatest benefit in out-of-hospital V-fib, though may help in other dysrhythmias[1]
  • Two most likely mechanisms of action:
    • Reduces cerebral metabolism by 6-8% per degree C
    • Reduces oxygen free radical production and lipid peroxidation
  • Cooling to 32-34ºC in initial studies, current studies suggest 36ºC equally beneficial[2]
  • Treatment should be initiated immediately after ROSC
    • Patient may be cooled concurrently with cardiac catheterization
  • Cooling should occur prior to CT scan if there is need for intracranial pathology workup
  • AHA recommends 12-24 hrs of cooling
  • NNT of ~6
  • Pediatrics[3][4]
    • Two large RTCs for TH, one in out-of-hospital and another in in-hospital arrests
    • Therapeutic hypothermia does not appear to provide a survival or improved neurological benefit[5]
      • In both studies, no difference in survival, function at 12 months post-arrest, blood product use, infection rates

Indications

Contraindications/Exclusions

Cooling

  • Cool to 32-34ºC as soon as possible (within 4 hours)
    • Strict maintenance of temperature at 36ºC may have similar benefits
  • Initiate rewarming 24 hrs after target temperature was reached
  • Cooling methods
    • Maintain at 32-34ºC with 2 cooling blankets to sandwich the pt, with sheets covering the blankets to protect skin
    • Alternatively, use heat exchange device (Icy Cath) or 4°C IVF at 30 cc/kg over 30 min
    • Cooling pads on the thighs and abdomen (Arctic Sun)
    • Supplement with ice packs to groin, chest, axillae, neck until 34ºC reached
  • Prevention of shivering and paralysis
    • Use benzodiazepines
    • Paralytics only if needed, and ensure patient fully sedated

Maintenance

Sedation

  • Fentanyl bolus 50 mcg IV every hour as needed for pain
  • Fentanyl IV infusion NSS
  • Propofol IV infusion
  • Lorazepam IV infusion
  • Lorazepam bolus 1mg IV every 2 hours as needed for agitation

Shivering

  • Prevention of shivering is important to avoid warming and needless oxygen consumption
  • May require train of four monitor with goal of 1-2/4 twitches with neuromuscular blockade
  • Lower doses of NMB work against shivering
  • Higher doses of NMB used to paralyze the diaphragm in these scenarios:
    • Need to decrease O2 consumption
    • Decrease plateau pressures
    • Hypoxemia is present
  • Consider meperidine q2hrs[7][8]:
    • 50mg for normal renal function
    • 25mg if CrCl < 30ml/min
  • Pancuronium IV infusion
    • Initiate before initiating cooling. Dosing recommendations: 0.1mg/kg loading dose followed by a continuous infusion of 0.33-2 mcg/kg/minute
    • Do not use in patients with renal and/or hepatic insufficiency
  • Cisatracurium for renal/hepatic impairment
    • 0.2mg/kg IV bolus
    • Followed by infusion at 1 mcg/kg/min, max of 3 mcg/kg/min
  • Columbia University anti-shivering protocol
Columbia shivering protocol.PNG

Rewarming

  • If severe dysrhythmia/BP instability/bleeding develops, rewarm
  • Discontinue K infusions (extracellular K increases)
  • Keep paralytic and sedative until rewarmed
  • Slow rewarm at 0.5°C to target of 36°C

General Management

Other Concerns

  • Head of bed at 30 degrees
  • Goal MAP 80 - 100 mmhg
  • Check skin q2-6 hrs for cold injury
  • Maintain normoglycemia
    • Do not treat hyperglycemia aggressively, as enzymatic functions are decreased at low temperatures, and rebound hypoglycaemia possible with rewarming
  • Replete K, Mg, Phos, Ca (hypothermia induced diuresis is expected)
  • Common unconcerning ECG findings during cooling - Osborne wave, HR < 40 bpm
  • Consider continuous EEG within 6 hrs, no later than 12 hrs after onset of cooling
  • Stress dose steroids for adrenal insufficiency
  • ?Seizure prophylaxis

Labs

  • ABG q6 hrs for duration of hypothermia
  • CBC, Coags, BMP, Mg, Phos q6 hrs for duration of hypothermia
    • Expect decreased K, Ca, Mg, Phos during, and rebound at rewarming
    • Hyperglycemia as metabolism slows at low temperature and body develops insulin resistance
  • Troponins, CK-MB q6 hrs x2 days
  • Lipase, LFTs (if abnormal, no need to intervene unless persistent after rewarming)
  • Other - Cortisol, UA, Pan-cultures, tox screen

ABG Interpretation

  • Rewarm ABG to 37C for analysis (controversial)
  • A warmed ABG from a hypothermic patient will show a higher PaO2, higher PaCO2, and a lower pH than that actually present in the patient’s blood in vivo
    • PaO2 is decreased by 5 mmHg for each degree below 37C
    • PaCO2 is decreased by 2 mmHg for each degree below 37C
    • Change in pH = 0.015 pH units per degree C change in temperature
      • If measured pH is 7.360 at 37C, then the pH at 34C is calculated as follows:
        • pH = [7.360 + (37-34)(0.015)] = 7.405

Monitoring

  • ECG q8 rule out ACS
  • Arterial line
  • Foley with temperature probe
  • CVP, ScvO2

Imaging

  • Consider head CT
  • Consider CTPE study

Other Considerations

  • GI prophylaxis
  • Modify prophylactic heparin or LMWH dosing as there is hypothermic coagulopathy[9]
    • No clear best way for monitoring of anticoagulation until further studies
    • Consider modified dosing:
      • Heparin 40 units IV bolus
      • Followed by 7 u/kg/hr during TH with scheduled repeated coags, plus or minus heparin levels

Disposition

  • ICU admission

External Links

See Also

Hypothermia Cardiac Arrest Links

References

  1. Nolan, et al. Therapeutic HypothermiaAfter Cardiac Arrest. Circulation. 2003; 108: 118-121.
  2. Nielsen N, et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. N Engl J Med. 2013; 369:2197-2206. DOI: 10.1056/NEJMoa1310519
  3. Moler FW et al. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. N Engl J Med 2017; 376:318-329January 26, 2017.
  4. Moler FW et al. Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children. N Engl J Med 2015; 372:1898-1908May 14, 2015.
  5. Mosler FW, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Eng J Med. 2015; 372:1898-1908.
  6. Song et al. Safely completed therapeutic hypothermia in postpartum cardiac arrest survivors. Am Jour Emer Med. June 2015. Volume 33, Issue 6, Pages 861.e5–861.e6.
  7. Choi HA, Ko SB, Presciutti M, et al. Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol. Neurocrit Care. 2011; 14(3):389-394.
  8. Fox Chase Cancer Center. Therapeutic HypothermiaProtocol. University of Pennsylvania. https://www.med.upenn.edu/resuscitation/docs/protocols/FoxChaseCancerCenterTherapeuticHypothermiaOrderSetafterCardiacArrest-latestrevision8-4-11.doc
  9. Wahby KA et al. Heparin dosing in critically ill patients undergoing therapeutic hypothermia following cardiac arrest. Resuscitation. 2014 Apr;85(4):533-7.