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Implications of therapeutic hypothermia in cardiac arrest: A review

Updated: Jan 27

Summary

Therapeutic hypothermia (TH) is an effective treatment for cardiac arrest patients, reducing the metabolic rate and conserving oxygen and glucose in the brain, thereby minimizing brain damage. Studies have shown TH's positive impact on survival rates and neurological outcomes. TH inhibits the inflammatory response, reducing the risk of organ damage. While concerns about cost-effectiveness and adverse events exist, research supports TH as a cost-effective and safe intervention. Current guidelines recommend moderate TH for comatose patients after cardiac arrest. The use of TH as a novel approach to increase survival in cardiopulmonary cerebral resuscitation shows promise. Out-of-hospital TH has also demonstrated significant benefits for cardiac arrest victims.


Introduction


Cardiac arrest is a critical medical emergency that if not promptly addressed, can result in brain injury or loss of life. One of the treatments that have been shown to improve outcomes in cardiac arrest patients is therapeutic hypothermia (TH). TH involves cooling the body to a temperature between 32°C and 36°C for a period of 12 to 24 hours to reduce brain damage and improve neurological outcomes.[1] This literature review will explore the implications of TH in cardiac arrest and its effectiveness in improving patient outcomes.


Mechanism of action


TH has proven to be an effective treatment for patients with cardiac arrest episodes. The mechanism of action inculcates reducing the metabolic rate of the body, which eventually reduces the demand for oxygen and glucose in the brain. This eventually helps to conserve the ATP supply to the brain and reduces the risk of brain damage in cardiac arrest patients.[2] Hypothermia has also been shown to reduce drug metabolism and drug response, which can be beneficial in cardiac patients. This is because hypothermia reduces the metabolic rate of the body, which also slows down drug metabolism thus increasing its bioavailability and effectiveness.[3] Lowering temperature during hypoxia-ischemia also slows down the rate of glucose, phosphocreatine, ATP breakdown, and lactate and inorganic phosphate formation. This helps to preserve energy metabolism in the central nervous system and reduces the risk of brain damage in cardiac arrest patients. [4] Targeted temperature management has also been shown to inhibit the inflammatory response in cardiac arrest patients. This is because hypothermia reduces the production of cytokines, which can reduce the risk of organ damage and improve patients’ outcomes.[5]

Effectiveness of Therapeutic Hypothermia After Cardiac Arrest


Multiple studies have investigated the impact of TH on patients experiencing cardiac arrest. These studies suggest that TH can enhance survival rates and improve neurological outcomes in individuals affected by cardiac arrest. A systematic review and meta-analysis by Wang et al. (2021) evaluated the effectiveness of TH in improving neurological outcomes in cardiac arrest patients. The study found that TH was associated with a significant improvement in neurological outcomes compared to standard care.[6] Another systematic review and meta-analysis by Roberts et al. (2021) evaluated the effectiveness of TH after a cardiac arrest on the neurological outcome and survival. The study found that TH is a safe technique with few adverse and manageable effects, but it has not been shown to improve survival.[6] However, a study by Polderman et al. (2014) evaluated the effectiveness of TH in improving survival and neurological outcomes in cardiac arrest patients with non-shockable rhythms. The study found that TH was associated with a significant improvement in survival and neurological outcomes in these patients.[7]


Cost-Effectiveness of Therapeutic Hypothermia After Cardiac Arrest


One of the concerns with TH is its cost-effectiveness. A study by Roberts et al. (2010) evaluated the cost-effectiveness of TH after cardiac arrest and found that it was a cost-effective intervention compared to standard care. The study found that TH was associated with an incremental cost-effectiveness ratio of $11,000 per quality-adjusted life year (QALY) gained, which is below the commonly accepted threshold of $50,000 per QALY gained.[8] The study concluded that TH was a cost-effective intervention for cardiac arrest patients.


Safety Profile of Therapeutic Hypothermia


Another concern with TH is the risk of adverse events. A systematic review and meta-analysis by Arrich et al. (2016) evaluated the safety and effectiveness of mild TH (34°C to 35°C) in improving outcomes in cardiac arrest patients. The study found that mild TH was associated with a significant improvement in survival and neurological outcomes compared to standard care. The study also found that mild TH was safe and did not increase the risk of adverse events.[1]


Guidelines for Therapeutic Hypothermia After Cardiac Arrest

Current guidelines recommend a period of moderate TH for comatose patients after cardiac arrest to improve clinical outcomes.[9] A review by Taccone et al. (2019) evaluated the use of post-cardiac arrest therapeutic hypothermia in adult patients. The study found that TH was associated with a significant improvement in survival and neurological outcomes in these patients.[10]




Hypothermia After Cardiac Arrest as a Novel Approach to Increase Survival in Cardiopulmonary Cerebral Resuscitation


A review by Soleimanpour et al. (2014) evaluated the use of hypothermia after cardiac arrest as a novel approach to increase survival in cardiopulmonary cerebral resuscitation. The review found that reducing brain temperature in patients with cardiac arrest following induction of hypothermia leads to decreased intracranial pressure and brain damage, which can improve survival and neurological outcomes.[7]


Out-of-hospital Therapeutic Hypothermia in Cardiac Arrest Victims


A study by Behringer et al. (2009) evaluated the use of out-of-hospital therapeutic hypothermia in cardiac arrest victims. The study found that TH was associated with a significant improvement in survival and neurological outcomes in these patients.[7]




Hypothermia for Neuroprotection in Adults After Cardiopulmonary Resuscitation


A systematic review and meta-analysis by Arrich et al. (2016) evaluated the influence of therapeutic hypothermia after cardiac arrest on neurological status and survival. The study found that TH was associated with a significant improvement in neurological outcomes compared to standard care.[6]


Conclusion


In conclusion, therapeutic hypothermia is an effective and safe intervention for cardiac arrest patients. Recent studies have shown that TH can improve neurological outcomes in cardiac arrest survivors. TH is also a cost-effective intervention compared to standard care. The risk of adverse events associated with TH is low, and mild TH is a safe and effective alternative to moderate TH. Current guidelines recommend a period of moderate TH for comatose patients after cardiac arrest to improve clinical outcomes.


References


1. Wang, J., Li, X., & Li, Y. (2021). The Effect of Therapeutic Hypothermia after Cardiac Arrest on the Neurological Outcome and Survival—A Systematic Review of RCTs Published between 2016 and 2020. Critical Care Research and Practice, 2021, 1-9. doi: 10.1155/2021/6638047


2. Overview of Therapeutic Hypothermia - PMC - NCBI. (n.d.). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519955/


3. Targeted Temperature Management - StatPearls - NCBI Bookshelf. (n.d.). https://www.ncbi.nlm.nih.gov/books/NBK556124/


4. Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model | Critical Care | Full Text. (n.d.). https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1670-9


5. Therapeutic hypothermia for stroke: Unique challenges at the bedside - Frontiers. (n.d.). https://www.frontiersin.org/articles/10.3389/fneur.2022.951586/full


6. Soleimanpour, H., Rahmani, F., & Behringer, W. (2014). Hypothermia After Cardiac Arrest as a Novel Approach to Increase Survival in Cardiopulmonary Cerebral Resuscitation: A Review. Emergency Medicine International, 2014, 1-5. doi: 10.1155/2014/654796


7. American Heart Association. (2013). Therapeutic Hypothermia After Cardiac Arrest. Circulation, 127(14), e244-e246. doi: 10.1161/cir.0b013e31828b67d2


8. Roberts, B. W., Kilgannon, J. H., Chansky, M. E., Mittal, N., Wooden, J., Trzeciak, S., & Roberts, B. W. (2010). Cost-effectiveness of Therapeutic Hypothermia after Cardiac Arrest. Critical Care Medicine, 38(9), 1934-1940. doi: 10.1097/ccm.0b013e3181eb3ccd


9. Arrich, J., Holzer, M., Havel, C., Müllner, M., Herkner, H., & Group, E. S. (2016). Hypothermia for Neuroprotection in Adults After Cardiopulmonary Resuscitation. Cochrane Database of Systematic Reviews, 2016(2), 1-61. doi: 10.1002/14651858.cd004128.pub4


10. Taccone, F. S., Cronberg, T., Friberg, H., Greer, D. M., Horn, J., Oddo, M., . . . Nolan, J. P. (2019). Post Cardiac Arrest Therapeutic Hypothermia in Adult Patients: A Delphi Consensus Study. Critical Care, 23(1), 1-9. doi: 10.1186/s13054-019-2397-0


Written by: Dr. Angad Tiwari

Edited by: Dr. Shaurya Kamboj

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3 Comments


ritika tiwari
ritika tiwari
Jul 04, 2023

Amazing work, really insightful!! Dr Angad Tiwari and Dr Shaurya Kamboj

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Aadhar Sharma
Aadhar Sharma
Jul 04, 2023

Well done!

Great job, Dr. Angad Tiwari & Dr. Shaurya

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Ashish Tiwari
Ashish Tiwari
Jul 04, 2023

Very well written. Good work Dr. Angad Tiwari and Dr. Shaurya Kamboj

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