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The TAME Cardiac Arrest Trial is a 1700 patient pragmatic, parallel group, randomised controlled trial evaluating the effect of mild hypercapnia in resuscitated patients post cardiac arrest. This study is coordinated by the ICC-CTN and ANZICS-RC.

Background and Rationale

Cardiac arrest is a common and dramatic event with major human and financial consequences. It is well understood that cardiac arrest leads to brain ischemia from lack of blood flow to the brain, and reperfusion injury following resuscitation. However, what is not widely appreciated is that, even after resuscitation, a state of poor blood flow to the brain known as cerebral hypoperfusion persists. This continued poor blood flow has been repeatedly shown to happen by many complex technologies (positron emission tomography, brain vessel ultrasound, jugular bulb oxygen saturation and cerebral oximetry).

A likely reason for cerebral hypoperfusion, and resultant cerebral hypoxia, after the heart has been restarted, is impaired cerebrovascular autoregulation; a reduction in brain blood vessel ability to adjust blood flow to meet the needs of the brain. Such impaired brain vessel auto-regulation may make even a normal arterial carbon dioxide tension (PaCO2) (the major factor that normally controls cerebral blood flow) unable to achieve and maintain best brain blood flow and oxygen levels. This may have an impact on neurological recovery and function. However, an increased PaCO2 (hypercapnia) can still increase brain blood flow in cardiac arrest patients. In this way, arterial carbon dioxide can be increased above normal levels to hopefully deliver best brain blood flow and brain recovery in patients admitted to the intensive care unit after a cardiac arrest.

Primary Aim

Supported by strong preliminary studies(1, 2, 3, 4), the TAME Cardiac Arrest Trial is a phase III multi-centre randomised controlled trial among resuscitated, mechanically ventilated out-of-hospital cardiac arrest patients admitted to ICU.

The TAME trial aims to determine whether increasing arterial carbon dioxide (PaCO2) to above normal levels [so-called targeted therapeutic mild hypercapnia (TTMH)] during the first 24 hours following resuscitated cardiac arrest, improves brain recovery at 6 months compared to current standard care [targeted normocapnia (TN)].

If the TAME Cardiac Arrest Trial confirms that TTMH is effective, its findings will improve the lives of many and transform clinical practice.

Study Design

The TAME Cardiac arrest study is a phase III multi-centre randomised controlled trial of mechanically ventilated out-of-hospital cardiac arrest patients admitted to ICU who are randomized to receive either TTMH or TN.

Primary Outcome

The primary outcome is the proportion of patients with a favorable neurological outcome at 6 months post-intervention as assessed by the Glasgow Outcomes Scale extended (GOSE).

Secondary Outcomes

Secondary outcomes of the trial include:

  • Mortality at ICU discharge, hospital discharge and at 6 months after randomisation

  • Functional recovery assessed using the modified Rankin scale and the Cerebral Performance Category  at 6 months after randomisation

  • Cognitive functional recovery assessed using the Montreal Cognitive Assessment (MoCA-blind); Informant Questionnaire on Cognitive Decline (IQCODE); Symbol Digit Modalities Test (SDMT) and 30-second chair test at 6 months after randomisation

  • Quality of life assessed by the EQ-5D-5L scale at 6 months after randomisation

  • Safety as determined as the proportion of pre-defined adverse events occurring between groups 

  • Health economic evaluation to determine differences in groups in Quality Adjusted Life Years (QALYs) at 6 months after randomisation

Participant Recruitment

TAME will screen and recruit 1,700 out-of-hospital cardiac arrest patients in multiple sites across several countries according to the following inclusion and exclusion criteria:

Inclusion criteria

  1. Adult (age ≥18 years or older)

  2. Out-of-hospital cardiac arrest of a presumed cardiac or unknown cause

  3. Sustained ROSC – defined as 20 minutes with signs of circulation without the need for chest compressions

  4. Unconscious (FOUR-score motor response of <4, not able to obey verbal commands after sustained ROSC)

  5. Eligible for intensive care without restrictions or limitations

  6. Within <180 minutes of ROSC

Exclusion criteria

  1. Unwitnessed cardiac arrest with an initial rhythm of asystole

  2. Temperature on admission <30oC

  3. On ECMO prior to ROSC

  4. Obvious or suspected pregnancy

  5. Intracranial bleeding

  6. Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy

Link to trial registration:

ClinicalTrials.gov - NCT03114033


TAME has begun screening and recruitment at several sites in Australia and Europe with more sites to commence soon.


  1. Eastwood GM, Young PJ, Bellomo R. The impact of oxygen and carbon dioxide management on outcome after cardiac arrest. Curr Opin Crit Care 2014;20:266-72

  2. Vaahersalo J, Bendel S, Reinikainen M, et al. Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest. Crit Care Med 2014;42:1463-70

  3. Eastwood GM, Tanaka A, Bellomo R. Cerebral oxygenation in mechanically ventilated early cardiac arrest survivors: The impact of hypercapnia. Resuscitation 2016;102:11-16

  4. Eastwood GM, Schneider AG, Suzuki S, et al. Targeted therapeutic mild hypercapnia after cardiac arrest. Resuscitation 2016;104:83-90.

Trial Coordination:

This study is coordinated by the ICC-CTN and ANZICS-RC.


For more information contact Kate Ainscough, the TAME project manager: This email address is being protected from spambots. You need JavaScript enabled to view it.