Temperature control after cardiac arrest

After a cardiac arrest, a patient who stays in a coma may be treated in intensive care with controlled body temperature. The TTM2 trial compared two ways of doing it in 1900 adults in a coma after a cardiac arrest outside hospital, of presumed cardiac or unknown cause: cooling to 33 degrees C and then controlled rewarming, or keeping a normal temperature and treating any fever early. After 6 months, deaths were about equal (50% with cooling, 48% with normothermia), and heart rhythm problems that affected circulation were more common with cooling (24% against 17%).

  • Intervention
  • In this atlas

Overview

Technical summary

The TTM2 abstract says targeted temperature management is recommended for patients after cardiac arrest but that the supporting evidence is of low certainty. The trial's comparator was targeted normothermia with early fever treatment, so the trial compares two temperature targets and does not test the absence of temperature management.

About this intervention

Type
Procedure
Mechanism
Cooling to 33 degrees C followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature of 37.8 degrees C or higher), as defined in TTM2.

Claims and evidence

Context Comatose adults resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause (TTM2)

Recipient
Adult
Population
Adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause (abstract wording). 1900 were randomly assigned and 1850 were evaluated for the primary outcome. The registry adds: unconscious with a FOUR-score below M4, stable return of spontaneous circulation for 20 minutes, eligible for intensive care without restrictions, and inclusion within 180 minutes of return of spontaneous circulation.
Care setting
Not stated in the abstract; the abstract gives no setting.
Geography
Registry locations in 14 countries; the registry also lists Luxembourg and the Netherlands as removed countries.
Life stage
Adults (abstract); the registry minimum age is 18 years and it gives no maximum age.
Follow-up
The primary outcome was death from any cause at 6 months (abstract). The registry gives 180 days.
Eligibility: 7 inclusion criteria; 6 exclusion criteria
Included
  • Out-of-hospital cardiac arrest (registry)
  • Presumed cardiac cause of the arrest (registry); the abstract says presumed cardiac or unknown cause
  • Unconscious with a FOUR-score below M4, not obeying verbal commands (registry)
  • Stable return of spontaneous circulation (20 minutes) (registry)
  • Eligible for intensive care treatment without restrictions (registry)
  • Inclusion within 180 minutes of return of spontaneous circulation (registry)
  • Age 18 years or older (registry)
Excluded
  • Unwitnessed cardiac arrest with an initial rhythm of asystole (registry)
  • Temperature on admission below 30 degrees C (registry)
  • On ECMO before return of spontaneous circulation (registry)
  • Obvious or suspected pregnancy (registry)
  • Intracranial bleeding (registry)
  • Severe chronic obstructive pulmonary disease with long-term home oxygen therapy (registry)
  • Effect Interventional Certainty not assessed

    In TTM2, an open-label trial with blinded assessment of outcomes, 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause were randomly assigned to targeted hypothermia at 33 degrees C followed by controlled rewarming, or to targeted normothermia with early treatment of fever (body temperature of 37.8 degrees C or higher). The primary outcome was death from any cause at 6 months. A total of 1850 patients were evaluated for it: 465 of 925 patients (50 percent) in the hypothermia group had died, as compared with 446 of 925 (48 percent) in the normothermia group (relative risk with hypothermia 1.04; 95 percent confidence interval 0.94 to 1.14; P=0.37). Of the 1747 patients whose functional outcome was assessed, 488 of 881 (55 percent) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score of 4 or more), as compared with 479 of 866 (55 percent) in the normothermia group (relative risk 1.00; 95 percent confidence interval 0.92 to 1.09). Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group (24 percent vs 17 percent, P<0.001); the incidence of other adverse events did not differ significantly. The authors conclude that targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia.

    Applies to Adult
    • Adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause (abstract wording). 1900 were randomly assigned and 1850 were evaluated for the primary outcome. The registry adds: unconscious with a FOUR-score below M4, stable return of spontaneous circulation for 20 minutes, eligible for intensive care without restrictions, and inclusion within 180 minutes of return of spontaneous circulation.
    • Not stated in the abstract; the abstract gives no setting.
    • Registry locations in 14 countries; the registry also lists Luxembourg and the Netherlands as removed countries.
    • Adults (abstract); the registry minimum age is 18 years and it gives no maximum age.
    Follow-up The primary outcome was death from any cause at 6 months (abstract). The registry gives 180 days.
    Certainty method
    Not assessed
    Limitations
    Abstract of the 2021 report only; the full text was not read (NEJM pages return HTTP 403 to scripts). The comparator was targeted normothermia with early treatment of fever, not an absence of temperature management, so the trial does not test whether managing temperature at all matters. The registry lists masking as TRIPLE but its description says the clinical team was not blinded to allocation; the abstract says open-label with blinded outcome assessment. 1850 of the 1900 randomized patients were evaluated for the primary outcome. The abstract names the Swedish Research Council and others as funders. PubMed lists no erratum for this record.
    Last checked
    2026-10-15
    Next evidence check due
    Not scheduled
    Sources and citations (21)
    1. Background Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    2. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    3. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    4. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    5. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    6. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    7. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    8. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    9. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    10. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    11. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    12. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    13. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    14. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    15. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    16. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    17. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    18. Supports Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    19. Background Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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    20. Background Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

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      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.
    21. Background Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) fetched 2026-10-15 through NCBI E-utilities. No PMC copy is listed. The full text and the version of record were not fetched (NEJM pages return HTTP 403 to scripts). · Published 2021-06-17 · DOI: 10.1056/NEJMoa2100591 · PMID: 34133859

      Locator
      Abstract, CONCLUSIONS, sentence 2
      How it applies
      The authors' conclusion in the abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      3d492d428372f6c023d3222d13d0effef2ab05fbf054da69978f394b011e99bf
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (PubMed disclaimer, fetched 2026-10-15 as ck-pubmed-disclaimer.html, hash only). Short factual quotations under 25 words, with the citation. Public text is quote, following Ben's decision of 2026-10-13 (medical-atlas-core issue 2) for PubMed and other NLM records.

Clinical links

Each link reports what one cited claim says about one population. "Evaluated for" means studied, not shown to work. These links do not show that anything is effective or right for you.

Record details

Record id
cardio:temperature-control-after-arrest
Content hash
9c3a42d6d6e158b5f03851dee4dcbba7633db9db89addbeb24c2cc385baa0c4e