Hypothermia in post cardiac arrest scenario

Rationale-

In acute stage-

  • Cerebral ischemia leads to increased “glutamate” in the neuronal cells leading to permanent neuronal hyper-excitation followed by cell death. This persistent stage of neuronal hyper-excitation leads to release of “NO” and other reactive oxygen species resulting in free radical cell damage and death. Hypothermia decreases the GLUTAMATE receptor expression and prevents the stage of persistent hyper-excitation, thereby decreases cell death.

  • It also decreases the metabolic demand of the body and may compromise for a state of low metabolic fuel supply consistent with post cardiac arrest scenario.

In sub-acute stage-

  • Decrease Inflammation: - Hypothermia causes decreased astrocyte and microglia cell activation. It decreases the pro-inflammatory mediators.

  • Inhibits Apoptosis: - Hypothermia decreases pro-apoptotic mediator expression, increases anti-apoptotic mediators and increases P53 expression and enhances tissue repair. 

  • Decrease damage to Blood Brain Barrier (BBB): - Hypothermia prevents the expression of “Metalloproteinase” and thereby limit damage to BBB.

  • Decrease Cerebral Oedema: - Hypothermia decreases NO synthesis.

Advantages-

  • Decreased pro-inflammatory response and limit brain damage.

  • Limit damage to BBB

  • Limit cerebral edema

  • Anticonvulsant activity 

 

Disadvantages-

  • CVS- Bradycardia, arrhythmia (prolong QTc), shock due to low cardiac output

  • Immunological- More susceptible to infection due to decreased immunity

  • Pharmacology-Altered drug metabolism and clearance- may need less dose than normal, increased drug toxicity with normal dosing

  • Hematological- Coagulopathy- Decreased rate of fibril synthesis, deranged platelet activation, Increased blood viscosity and hematocrit 

  • Metabolic-Hyperglycemia, shivering

Evidence-

Bernard etal 2002,included post VF arrest patients, enrolled patients to hypothermia (temp 33oC for 12 hours) vs no hypothermia, demonstrated a good neurological outcome, ARR 23% and NNT of 4.5. Though it was small trial with issues of concealment bias, but it represented the setting stone for hypothermia post cardiac arrest.

The MCRC HACA trial [Hypothermia After Cardiac arrest (2002)] found an ARR of 24% of poor neurological outcome and a NNT of 4.

A Cochrane review in 2016 including the TTM trial, concluded that therapeutic hypothermia(Temp<340C) provided a better neurological outcome (moderate quality evidence). They also demonstrated a 30% survival benefit in hypothermia group compared to no cooling. No significant increase in complication (i.e pneumonia, hypokalemia).

Most recent evidence- TTM trial, 2013

Nielsen et al, 36 ICUS in Europe and Australia, MCRCT

Compared 33 oC with 36 oC.

Exclude patients who are coagulopathic, suspected or proven intra-cranial bleed, pregnant and who presented with asystole.

Target achieved in less than 6hours, targeted temp is maintained for 36 hrs and rewarming done at 0.250C per hour.

No significant difference in mortality at 180 days, no difference in neurological outcome.

The higher temp group had a lesser duration of mechanical ventilation, episodes of hypokalemia. Interestingly there was no difference in outcome demonstrated when shockable is compared to non-shockable rhythm.

The major issue with the trial was a very short time for commencement of CPR (<1min) which raises the question whether patients presenting with a longer delay in CPR may have a better outcome with a TTM of 330C.

 

Guideline statement-

-Cool to 32-340C (89.6-93.20F) for 12-24 hours

- Class 1, Level B- evidence

Comatose patients (Lack of meaningful response to verbal commands) with VF/VT OHCA

-Class 2, Level B evidence OHCA, for other rhythms 

Should include in management of both shockable & non-shockable rhythm cardiac arrest though there is paucity of evidence for non-shockable rhythm cardiac arrest.

  • ARC-2016- Recommends TTM (32-360C) for at least 24 hours for all post cardiac arrest comatose patients (Shockable, non-shockable, OHCA or IHCA).

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