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Targeted Temperature Management After Cardiac Arrest—Commentary

3/16/2017 Diane M. Birnbaumer, MD, Professor of Medicine, Emeritus, David Geffen School of Medicine at UCLA; Senior Clinical Educator, Department of Emergency Medicine, Harbor-UCLA Medical Center

Current guidelines recommend considering the use of targeted temperature management (ie, controlling the core temperature to a target temperature typically between 33 and 36° C) for both adult and pediatric patients who were resuscitated after suffering cardiac arrest and remain comatose. However, a recent article published in the New England Journal of Medicine (1) suggests this intervention may be futile in children who suffer in-hospital cardiac arrest.     

In a trial involving 37 children’s hospitals, hospitalized children between the ages of 48 hours and 18 years resuscitated after suffering in-hospital cardiac arrest who remained comatose were randomized to therapeutic hypothermia (target temperature 33° C) or therapeutic normothermia (target temperature 36.8° C). The study was terminated early due to futility after results in 329 children showed no benefit in survival at 12 months and no significant differences in neurologic outcomes. No significant differences in adverse events were found between the groups. 

The concept of targeted temperature management after cardiac arrest has been a hot topic since 2002 when two small studies suggested improved neurologic outcomes after its use in adult patients remaining comatose after resuscitation from out-of-hospital cardiac arrest (OOHCA—2, 3). These promising results led to the rapid integration of this intervention into guidelines for post-resuscitation treatment. Since the initial enthusiasm, however, subsequent studies, including a larger randomized trial in adults, showed minimal benefit of this treatment on either mortality or neurologic outcomes (4, 5).  Most OOHCA data in children consist of case series or database reviews, but a 2015 study by Moler et al of 295 children with OOHCA showed no benefit of therapeutic hypothermia in these patients (6). The current study by Moler et al suggests it also is not useful in children with in-hospital cardiac arrest.

So, should targeted temperature management be removed from post-resuscitation treatment guidelines in adults and children? Maybe not yet. As a sole intervention, results appear disappointing, but when integrated as part of an optimal post-resuscitation treatment protocol that includes percutaneous coronary intervention (when indicated), optimized oxygenation and blood pressure, glucose monitoring, and rapid intervention in cases of suspected infection, it may be useful. In fact, focusing on temperature management, in particular, preventing hyperthermia, may prove to be the most important aspect of temperature control in these patients. And while critics cite adverse outcomes such as pneumonia and other infections in these patients as an argument against its use, data suggest that the increased risk of pneumonia does not have a significant impact on outcomes. 

For now, guidelines continue to recommend targeted temperature management in these patients and, as such, should continue to be used. As more studies address efficacy, however, keep an eye out for changes in guidelines if further studies continue to suggest this intervention is useless. 

References

  1. Moler FW, Silverstein FS, Holubkov R, et al: Therapeutic hypothermia after in-hospital cardiac arrest in children. N Engl J Med 376:318–329, 2017,
  2. The Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556, 2002.
  3. Bernard SA, Gray TW, Buist MD, et al: Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563, 2002.
  4. Nielsen N, Wetterslev J, Cronberg T, et al: Targeted temperature management at 33° C versus 36° C after cardiac arrest. N Engl J Med 369;2197–2206, 2013.
  5. Lilja G, Nielsen N, Friberg H, et al:  Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33° C versus 36° C.  Circulation 131:1340–1349, 2015.
  6. Moler FW, Silverstein FS, Holubkov R, et al:  Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med 372:1898–1908, 2015.
 
Diane Birnbaumer

Targeted Temperature Management After Cardiac Arrest—Commentary

3/16/2017 Diane M. Birnbaumer, MD, Professor of Medicine, Emeritus, David Geffen School of Medicine at UCLA; Senior Clinical Educator, Department of Emergency Medicine, Harbor-UCLA Medical Center

Current guidelines recommend considering the use of targeted temperature management (ie, controlling the core temperature to a target temperature typically between 33 and 36° C) for both adult and pediatric patients who were resuscitated after suffering cardiac arrest and remain comatose. However, a recent article published in the New England Journal of Medicine (1) suggests this intervention may be futile in children who suffer in-hospital cardiac arrest.     

In a trial involving 37 children’s hospitals, hospitalized children between the ages of 48 hours and 18 years resuscitated after suffering in-hospital cardiac arrest who remained comatose were randomized to therapeutic hypothermia (target temperature 33° C) or therapeutic normothermia (target temperature 36.8° C). The study was terminated early due to futility after results in 329 children showed no benefit in survival at 12 months and no significant differences in neurologic outcomes. No significant differences in adverse events were found between the groups. 

The concept of targeted temperature management after cardiac arrest has been a hot topic since 2002 when two small studies suggested improved neurologic outcomes after its use in adult patients remaining comatose after resuscitation from out-of-hospital cardiac arrest (OOHCA—2, 3). These promising results led to the rapid integration of this intervention into guidelines for post-resuscitation treatment. Since the initial enthusiasm, however, subsequent studies, including a larger randomized trial in adults, showed minimal benefit of this treatment on either mortality or neurologic outcomes (4, 5).  Most OOHCA data in children consist of case series or database reviews, but a 2015 study by Moler et al of 295 children with OOHCA showed no benefit of therapeutic hypothermia in these patients (6). The current study by Moler et al suggests it also is not useful in children with in-hospital cardiac arrest.

So, should targeted temperature management be removed from post-resuscitation treatment guidelines in adults and children? Maybe not yet. As a sole intervention, results appear disappointing, but when integrated as part of an optimal post-resuscitation treatment protocol that includes percutaneous coronary intervention (when indicated), optimized oxygenation and blood pressure, glucose monitoring, and rapid intervention in cases of suspected infection, it may be useful. In fact, focusing on temperature management, in particular, preventing hyperthermia, may prove to be the most important aspect of temperature control in these patients. And while critics cite adverse outcomes such as pneumonia and other infections in these patients as an argument against its use, data suggest that the increased risk of pneumonia does not have a significant impact on outcomes. 

For now, guidelines continue to recommend targeted temperature management in these patients and, as such, should continue to be used. As more studies address efficacy, however, keep an eye out for changes in guidelines if further studies continue to suggest this intervention is useless. 

References

  1. Moler FW, Silverstein FS, Holubkov R, et al: Therapeutic hypothermia after in-hospital cardiac arrest in children. N Engl J Med 376:318–329, 2017,
  2. The Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556, 2002.
  3. Bernard SA, Gray TW, Buist MD, et al: Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563, 2002.
  4. Nielsen N, Wetterslev J, Cronberg T, et al: Targeted temperature management at 33° C versus 36° C after cardiac arrest. N Engl J Med 369;2197–2206, 2013.
  5. Lilja G, Nielsen N, Friberg H, et al:  Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33° C versus 36° C.  Circulation 131:1340–1349, 2015.
  6. Moler FW, Silverstein FS, Holubkov R, et al:  Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med 372:1898–1908, 2015.