Therapeutic hypothermia has been used since the days of Hippocrates who advised using snowpacks for wounded soldiers.[1] Other wartime surgeons found when wounded soldiers were placed near the campfire, they had a higher likelihood of dying compared to those in colder areas.1 Fast forward to the 1930s, reports of drowning victims surviving after long periods of asphyxia piqued the interest of researchers to determine what role inducing hypothermia may play surrounding cardiac care.1
The intentional use of inducing hypothermia has been utilized during cardiac surgery since the 1950s due to the protective benefits against hypoxic-ischemic brain injuries.[2] This has led to researchers exploring the benefits of using targeted temperature management in patients post cardiac arrest, or in patients who lack a heart rhythm causing a loss of all heart function.[3]
Cardiac arrest is when the heart stops beating and can cause a person to stop breathing and become unconscious.3 Over the years there have been many trials with varying results when it comes to inducing hypothermia for cardiac arrest patients, also called targeted temperature management, and patient outcomes.
Today’s article reviews some of these trials, their limitations, as well as implications for clinical application of temperature management after cardiac arrest.
What is Targeted Temperature Management and How is it Done?
Targeted temperature management (TTM) is the practice of quickly reducing the body core temperature from 32°C to 34°C in an effort to reduce neurological damage post cardiac event. TTM involves three phases: induction, maintenance, and rewarming.1
There are different TTM methods including:1
- Conventional cooling – involves using ice packs around the patient and infusing cold saline through a peripheral IV.
- Surface cooling – blankets or pads that have cold air or fluid circulating through them are wrapped around the patient.
- Core cooling - involves infusing cold saline through central venous access (the most effective method).
What Does the Research Say About Targeted Temperature Management?
A 2013 trial of 950 patients who experienced out-of-hospital cardiac arrest and arrived to the ICU unconscious found no benefit in inducing therapeutic hypothermia.4 The targeted temperatures compared were 33°C and 36°C and there was no difference in 180-day mortality or neurological function.[4]
In 2021, a similar trial explored the benefit of therapeutic hypothermia in 1,900 patients with coma after an out-of-hospital cardiac arrest.[5] The goal was also 33°C for the hypothermia group.
The two outcomes measured were death at six-months and functional assessment using the modified Rankin scale. Like the 2013 trial, there were no benefits regarding mortality or function in the hypothermia group.5
Also worth noting, arrhythmias were more common in the hypothermia group.5
When looking at ventricular fibrillation patients that had been resuscitated after cardiac arrest and were not unconscious or in coma, a small study of 136 patients found a benefit in therapeutic hypothermia reducing mortality and improved neurological outcome.[6] At six months, mortality for the hypothermia group was 41%, and 55% of these patients had favorable neurological outcomes. This is compared to 55% mortality and only 39% favorable neurological function for the normothermia group.6
One of the most recent studies, the HYPERION trial in 2019, found using targeted therapeutic hypothermia in nonresponsive patients after a cardiac arrest with a non-shockable rhythm led to favorable outcomes.[7] This trial also looked at neurological function 90-days post event as well as mortality. Neurological function was measured using the cerebral performance category score. Patients in the therapeutic hypothermia group (33°C) had higher performance scores at 90 days although there was no difference in 90-day mortality.7
Although benefits were found in the HYPERION trial, it was considerably smaller compared to some of the others with only 581 participants.7
Temperature Management Challenges Post Cardiac Arrest
There are risks associated with TTM which must be considered when determining the best plan for a patient. Existing cardiac dysfunction can be amplified with the drastic core temperature change and arrhythmias can happen post resuscitation.1 There is also a risk of cold-induced diuresis.1
Electrolyte abnormalities often happen during the initial and rewarming phases of TTM, and there can be an increased risk of infection due to the suppression of natural pro-inflammatory actions.1
The Future of Temperature Management for Cardiac Arrest Patients
While rapidly decreasing body temperature has been shown to be effective in mice, the trouble has been finding a way to reduce the body temperature in human trials as quickly as in animal trials.2 There are also other variables including comorbidities and whether the patient had a shockable versus non-shockable rhythm to consider.2
The International Liaison Committee on Resuscitation (ILCR) is a forum of international groups including the American Heart Association and the European Resuscitation Council, and they make recommendations around resuscitation efforts.
Their 2015 report recommends attempting TTM for patients who have experienced cardiac arrest, with a targeted temperature of around 33°C.2 However, due to additional research, the committee shifted their recommendation from inducing hypothermia to only actively preventing fever for 72 hours post cardiac event.2
Due to the varied results from trials surrounding temperature management, there is a clear need for additional research to determine how beneficial it is for patients post cardiac arrest. There is also a need for initial studies regarding active fever reduction methods as a potential alternative to TTM that has fewer risks of unwanted effects.
Summary
- Inducing hypothermia has been used in medicine for hundreds of years to reduce death post trauma, support cardiac surgery and, most recently, to try and reduce the risk of brain damage post cardiac arrest.
- Although many trials have been done surrounding this topic, there is still no solid evidence targeted temperature management is consistently beneficial to patients.
- Because of the risks associated with targeted temperature management and the lack of consistent benefits shown in trials, more research is needed to determine the role it plays in post cardiac arrest patient care.
- A similar topic, currently lacking sufficient research, is whether or not actively preventing fever in patients post cardiac arrest could be beneficial – a practice currently recommended by the ILCR guidelines.
References
[1] Omairi, A & Pandey, S. (2022). Targeted temperature management. National Library of Medicine: StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK556124/. Accessed March 5, 2023.
[2] Sandroni, C, Natalini, D, & Nolan, J. (2022). Temperature control after cardiac arrest. Critical Care, 26:361.
[3] Mayo Clinic. (2023). Sudden cardiac arrest. Mayo Clinic: Patient Care & Health Information. https://www.mayoclinic.org/diseases-conditions/sudden-cardiac-arrest. Accessed March 5, 2023.
[4] Nielsen, N et al. (2013). Targeted temperature management at 33°C versus 36°C after cardiac arrest. The New England Journal of Medicine, 369:2197-2206.
[5] Dankiewicz et al. (2021). Hypothermia versus normothermia after out-of-hospital cardiac arrest. The New England Journal of Medicine, 384:2283-2294.
[6] Holzer, M. (2002). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. The New England Journal of Medicine, 246:549-556.
[7] Lascarrou, JB et al. (2019). Targeted temperature management for cardiac arrest with nonshockable rhythm. The New England Journal of Medicine, 381:2327-2337.