Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest

  • End date
    Dec 24, 2022
  • participants needed
  • sponsor
    Australian and New Zealand Intensive Care Research Centre
Updated on 24 January 2021
carbon dioxide
traumatic brain injury


The TAME Cardiac Arrest trial will study the ability of higher arterial carbon dioxide (PaCO2) levels to reduce brain damage, comparing giving patients 'normal' to 'slightly higher than normal' blood PaCO2 levels and assessing their ability to return to normal life-tasks. It will be the largest trial ever conducted in heart attack patients in the intensive care unit. This therapy is cost free and, if shown to be effective, will improve thousands of lives, transform clinical practice, and yield major savings.


Cardiac arrest is a common and catastrophic event with substantial human and financial costs. It is well understood that cardiac arrest leads to brain injury. However, what is not widely appreciated is that, after circulation has been restored, cerebral hypoperfusion continues. Ongoing cerebral vasoconstriction and cerebral hypoxia has been demonstrated using technologies that include positron emission tomography, ultrasound, jugular bulb oxygen saturation and cerebral oximetry.

A likely mechanism responsible for sustained early cerebral hypoperfusion relates to impaired cerebrovascular auto-regulation. Such impaired cerebral auto-regulation may make even a normal arterial carbon dioxide tension (PaCO2) (the major physiological regulator of cerebral blood flow) insufficient to achieve and maintain adequate cerebral perfusion and, consequently, cerebral oxygenation. However, PaCO2 is the major determinant of cerebral blood flow and an increased PaCO2 (hypercapnia) markedly increases cerebral blood flow. Moreover, arterial carbon dioxide is modifiable and, as such, is a potential therapeutic target.

The TAME Cardiac Arrest Trial is a definitive phase III multi-centre randomised controlled trial in resuscitated cardiac arrest patients. This trial will determine whether targeted therapeutic mild hypercapnia (TTMH) applied during the first 24 hours of mechanical ventilation in the intensive care unit (ICU) improves neurological outcome at 6 months compared to standard care (targeted normocapnia (TN).

Supported by compelling preliminary data, significant improvements in patient outcomes are achievable with this proposed simple and cost free therapy. Recruiting 1,700 patients, for multiple sites in many countries, this will be the largest trial ever conducted involving resuscitated cardiac arrest patients admitted to the ICU. If the TAME Cardiac Arrest Trial confirms that TTMH is effective, its findings will improve the lives of many, transform clinical practice and yield major economic gains worldwide.

Condition Out-of-Hospital Cardiac Arrest, out-of-hospital cardiac arrests, out of hospital cardiac arrest
Treatment Targeted therapeutic mild hypercapnia, Targeted normocapnia (Standard care)
Clinical Study IdentifierNCT03114033
SponsorAustralian and New Zealand Intensive Care Research Centre
Last Modified on24 January 2021


Yes No Not Sure

Inclusion Criteria

Adult (age 18 years or older)
Out-of-hospital cardiac arrest of a presumed cardiac or unknown cause
Sustained ROSC - defined as 20 minutes with signs of circulation without the need for chest compressions
Unconscious (FOUR-score motor response of <4, not able to obey verbal commands after sustained ROSC) (Appendix D)
Eligible for intensive care without restrictions or limitations
Within <180 minutes of ROSC

Exclusion Criteria

Unwitnessed cardiac arrest with an initial rhythm of asystole
Temperature on admission <30oC
On ECMO prior to ROSC
Obvious or suspected pregnancy
Intracranial bleeding
Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy
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