Therapeutic hypothermia


 * Associate Editor(s)-In-Chief: ; Priyamvada Singh, M.B.B.S. [mailto:psingh@perfuse.org]

Overview
Brain temperature during the first 24 hours after resuscitation from cardiac arrest has a significant effect on survival and neurological recovery. Fever (Tmax) during the first 48 hours is associated with a decreased chance of good neurological recovery (OR 2.26 [1.24, 4.12] for each 1°C over 37°C). Cooling to 32-34°C for 24 hours decreases chance of death (OR 0.74 [0.58, 0.95]) and increases chance of good neurological recovery (OR 1.40 [1.08,1.81]). Cooling to 32-34°C for 12 hours increases chance of good neurological recovery (OR 2.65 [1.02, 6.88]).

Mechanism of Effects

 * Hypothermia activates the sympathetic nervous system causing vasoconstriction and shivering.
 * Shivering increases O2 consumption by 40-100%.
 * Sedatives, opiates, and neuromuscular blockers can counteract these responses and enhance the effectiveness of active cooling.
 * However, initiating paralysis in a patient who is already hypothermic should be avoided as it can result in a precipitous drop in core body temperature.
 * Elderly patients will cool more quickly than younger or obese patients.
 * Hypothermia shifts the oxyhemoglobin curve to the left and may result in decreased O2 delivery.
 * However, the metabolic rate is also lowered, decreasing O2 consumption / CO2 production, cardiac output and cerebral blood flow.
 * Ventilator settings may need to be adjusted due to decreased CO2 production, using temperature corrected blood gases.
 * Hypothermia initially causes sinus tachycardia, then bradycardia. With temp <30º C there is an increased risk for arrhythmias. With temp <28º C there is an increased risk for ventricular fibrillation. The severely hypothermic myocardium (<30°C) is less responsive to defibrillation and medications. Therefore it is extremely important to keep temp >30ºC.
 * Hypothermia can induce coagulopathy which is treatable with platelets and FFP.
 * Hypothermia-induced diuresis is to be expected and should be treated aggressively with fluid and electrolyte repletion. Magnesium, phosphorus and potassium should be monitored closely and maintained in the normal (because it will rebound to very high) range.
 * Decreased insulin secretion and sensitivity leads to hyperglycemia, which should be treated aggressively.
 * Re-warming too rapidly can cause vasodilation, hypotension, and rapid electrolyte shifts.

Eligibility Criteria for Post-Cardiac Arrest Therapeutic Hypothermia

 * Meets eligibility criteria for Post-Cardiac Arrest Care Pathway
 * Comatose at enrollment with a Glasgow Coma Motor Score <6 pre-sedation (i.e., patient doesn’t follow commands)
 * No other obvious reasons for coma
 * No uncontrolled bleeding
 * Hemodynamically stable with no evidence of:
 * Uncontrollable dysrhythmias
 * Severe cardiogenic shock
 * Refractory hypotension (MAP <60 mm Hg) despite preload optimization and use of vasoactive medications


 * No existing, multi-organ dysfunction syndrome, severe sepsis, or comorbidities with minimal chance of meaningful survival independent of neurological status

Other indications
Therapeutic hypothermia is an active area of research. Many trials are underway to see its possible benefits in conditions other than post-cardiac arrests like:


 * Traumatic brain injury - Benefits are seen in patients with elevated intra cranial pressure, and those treated with long-term hypothermia. However, studies on pediatrics population found an increase in rates of pulmonary hypertension and seizures in pediatric patients treated with therapeutic hypothermia


 * Traumatic spinal cord injury


 * Acute stroke


 * Pediatric cardiac arrest


 * Neonatal hypoxic ischemic encephalopathy

Therapeutic goals
Therapeutic hypothermia is practiced in many tertiary hospitals. The treatment goals followed in most of them are:


 * Goal temperature- 32-34 degree celsius
 * Active cooling for 24 hours.
 * Rapid achievement of cooling temperature (within 3-4 hours)
 * Rewarming
 * Slow rewarming (may take 8-10 hours) is preferred over rapid rewarming as the latter may cause dilatation of the vessel and result in hypotension
 * It can be achieved by discontinuation of methods used for cooling like cooling blankets, ice and drugs
 * Continuous blood pressure monitoring should be done to avoid development of hypotension
 * It should be started 24 hours after the time of initiation of cooling
 * Slow rewarming @ 0.3-0.5ºC/hr
 * Target rewarming temperature 36°C

Contraindications

 * Prolonged arrest time (> 60 minutes)
 * Thrombocytopenia or other coagulopathies (hypothermia may impair the clotting factors)
 * Pregnancy (Therapeutic hypothermia can potentially be performed on pregnant female in consultation with OB/Gyn)
 * Major surgery within 14 days (it may increase risk of infections and bleeding in this group of patients)
 * Sepsis and other systemic infections (decreased immune function due to hypothermia)
 * Coma from other causes like drug intoxication
 * Patients who have signed a 'Do not resuscitate'(DNR)

Surface cooling with ice packs

 * Head, neck, axilla, and groin are preferred sites (these areas have good heat exchange)
 * Advantage - Inexpensive
 * Disadvantages
 * Difficulties in achieving and maintaining rapid rates of cooling
 * Variable and unpredictable rates of cooling

Blankets or surface heat-exchange device and ice

 * During cooling phases blankets, the cooling device's (heat-exchange pads) and ice packs are applied. Ice packs are removed once target temperature is achieved. The temperature is maintained with blanket or heat exchange pads.
 * Disadvantages
 * Difficulties in achieving and maintaining rapid rates of cooling
 * Variable and unpredictable rates of cooling

Surface cooling helmet

 * The helmet has a solution of aqueous glycerol that helps in achieving hypothermia.
 * Disadvantage - Slow, unpredictable attainment of target temperature

Catheter based internal cooling methods / Endovascular heat-exchange catheters

 * Devices available: Celsius Control System and Cool Line System
 * Placed in femoral vein
 * Advantages
 * Both endovascular cooling and rewarming are faster
 * Good at maintaining target temperature
 * Low rates of complications
 * Minimization of shivering
 * Decreased need for chemical paralysis

Infusion of cold fluids

 * Achieved by infusion of normal saline or lactated Ringer solution
 * Advantage - Rapid cooling
 * Disadvantage - rate of cooling is unpredictable
 * No increased risks of pulmonary edema, cardiac arrhythmias or other major complications was found,.

Complications

 * Arrhythmias
 * Sepsis
 * Bleeding, coagulopathy
 * Electrolytes disturbances
 * Shivering