Postcardiac Arrest Therapeutic Hypothermia

It’s April 2011 and time for @EBMedicineʼs Emergency Medicine Practice monthly review. This month the focus on the hottest of hot topics, therapeutic hypothermia.

Constantine M. (2011).Current Evidence In Therapeutic Hypothermia For Postcardiac Arrest Care. Emergency Medicine Practice, 13(4). [Abstract and subscription link]

Therapeutic Hypothermia (TH) or “Induced Hypothermia” is a treatment whereby a patient is deliberately cooled to between 32-33.9 °C (90-93°F), particularly following cardiac arrest. The aim is to reduce hypoperfusion (and reperfusion) injury post-arrest, especially to the brain, but also to other organ systems (including heart, liver, kidney). Despite initially being studied in out-of-hospital VF or VT arrest, it should be considered for all who develop return of spontaneous circulation (ROSC) following other types of cardiac arrest. TH may also be considered for hypoxic arrest or traumatic brain injury. In the early research, temperatures below 30°C (86°F) were associated with greater adverse effects, and the term “moderate therapeutic hypothermia” has been used to describe the above temperature range.

So, what are some of the insights can we can glean from this month’s review? Yep, that’s right, it’s time for a good ole LITFL Q&A review…


Q1. What are the current indications and contraindications for therapeutic hypothermia?

Inclusion and exclusion criteria vary between institutions.

The following are suggested inclusion criteria:

  • Post cardiac arrest (any cause)
  • ROSC < 30 mins from team arrival
  • Time < 6 hours from ROSC
  • Patient is comatose
  • MAP >= 65mmHg

Exclusions may include:

  • Advanced directive stipulating DNR (absolute)
  • Traumatic arrest
  • Active bleeding (including intracranial)
  • Pregnancy, recent major surgery, severe sepsis

Q2. What is the mechanism of post-arrest organ injury (aka postcardiac arrest syndrome)?

Postcardiac arrest syndrome was once thought to be generally related to production of free radicals, although the pathophysiology is more complex. Hypoperfusion and ischaemia cause a cascade of events — disruption of homeostasis, free radical formation and protease activation among other things. The disruption may continue for hours or days. Hypothermia may slow down this cascade.

There are four main clinical considerations in postcardiac arrest syndrome.

  1. Postcardiac Arrest Brain Injury —
    Disruption on both a micro- and macro- circulatory levels may result in either ischaemia or hyperaemia.
  2. Postcardiac arrest myocardial dysfunction —
    Although the heart initially becomes hyperkinetic, likely due to circulating catecholamines, global hypokinesis often follows.
    Usually resolves within 72 hours.
  3. Systemic Ischaemia/Reperfusion Response —
    The response of the body is similar to the septic shock with activation of the immune and complement systems, and release of inflammatory cytokines and a wide range of cellular responses.
  4. Persistent precipitating pathology —
    The cause of the arrest may continue to impact physiological parameters.

Q3. When should TH be initiated?

Once a patient is considered suitable for TH, it should be commenced as soon as possible.

Most cardiac arrests occur outside of hospital, and paramedical services are increasingly initiating cooling. This should be continued (or initiated if not already), in the Emergency Department and through to the Intensive Care Unit. Clearly this requires a co-ordinated approach.

Cooling can be done via external means (ice packs, cooling blankets) or internal means (Cold IV fluids at 4°C (39°F)).

Q4. What are the phases of TH?

There are 3 phases: Induction, Maintenance and Rewarming


  • Aim to reduce the core body temperature to between 32-34°C (90-93°F) – within 6 hours


  • Maintain core body temperature for 12-24 hours.


  • Either controlled or passive rewarming to normothermia 37°C (98.6°F)
  • 0.2-0.5°C (0.5-1°F) per hour – over 8-12 hours

Q5. What are the benefits of TH?

There were two randomized controlled trials of TH, published in 2002. Bernard, et al looked at 77 patients, with an Absolute Risk Reduction (ARR) for death or severe disability of 23%, number needed to treat (NNT) was 4.5. The Hypothermia After Cardiac Arrest Group looked at 273 patients, with an ARR for unfavourable neurological outcome of 24%, and NNT of 4. The Cochrane Database’s systematic review in 2009 found an NNT of 5 to 7.

Hence, there is a good likelihood that TH improves the outcome in about 1 in 5 patients (or 6, according to Cochrane and Aspirin and thrombolysis for MI pale in comparison.

Q6. What electrolyte or metabolic abnormalities are common with TH?

On top of the precipitating disease pathology, TH may independently alter the patients’ physiology.

Potassium and magnesium levels are seen to drop, and should be replaced. Other normal findings are low WCC, and high PT/APPT and LFTs, which do not require treatment. Blood gas analysis may show low pH and HCO3- and high pCO2 and pO2. These values may or may not be temperature adjusted,  depending on your blood-gas analyser.

Drug metabolism is generally slowed, leading to increased half-life, and hence drug accumulation.

Q7. What ECG and cardiac changes occur with TH?

Patients may become bradycardic, hypotensive and drop their cardiac output (which is thankfully matched by reduced metabolic demand). AF is common, although severe dysrhythmias are more common below 30°C (86°F). Other ECG changes in hypothermia include prolongation of the PR, QRS and QT intervals, as well as Osborne waves (or J-waves).

Q8. What other problems are there with TH?

TH may induce cold diuresis, leading to volume loss.

Although coagulopathy  and platelet dysfunction is a known side effect of hypothermia, there has been no observed difference in adverse bleeding events following TH, even in those who underwent PCI or thrombolysis in the immediate post-arrest period. Furthermore, in patients with intracerebral bleeding, TH has not been shown to increase morbidity or mortality.

Aspirin, thrombolysis and other anticoagulation methods should therefore be used if indicated.

Shivering occurs at a core temperature of approx 35.5°C (96°F) and may be counterproductive to induction of cooling. Treatment includes adequate sedation, followed by muscle paralysis if needed.

Additional references

  • Arrich J, Holzer M, Herkner H, Müllner M. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database of Systematic Reviews 2009. PMID: 19821320
  • Bernard SA, Gray TW, Buist MD et al. Treatment of comatose survivors of out-of -hospital cardiac arrest with induced hypothermia. N Eng J Med 2002;346:557-63 PMID: 11856794
  • Bernard SA, Smith K, Cameron P, et al. Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest, a randomized controlled trial. Circ. 2010; 122:737-42. PMID: 20679551
  • Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009; 37[S]: S186-S202. PMID: 19535947
  • Hypothermia after cardiac arrest study group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Eng J Med 2002;346:549-56. PMID: 11856793
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  1. Ainslie says

    Thanks G. Why didn’t I commission you to summarise all topics for me before I started the fellowship marathon? Bit late now … clinicals in one week! A