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Targeted therapeutic mild hypercapnia after resuscitated cardiac arrest: a Phase III multi-centre randomised controlled trial

Cardiac arrest is a common and catastrophic event with substantial human and financial costs. Approximately 10,000 people die from cardiovascular disease every year in Ireland. It is estimated that 5,000 of these deaths are from a sudden cardiac arrest.
It is well recognised that cardiac arrest leads to brain injury. However, what is not widely appreciated is that, even 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.
Arterial carbon dioxide tension (PaCO2) is the major physiological regulator of cerebral blood flow. A likely mechanism responsible for sustained early hypoperfusion relates to impaired cerebrovascular auto-regulation. Such impaired auto-regulation may make even a normal arterial carbon dioxide tension (PaCO2) insufficient to achieve and maintain adequate cerebral perfusion and, consequently, cerebral oxygenation. However, an increased PaCO2 (hypercapnia) markedly increases cerebral blood flow. Moreover, arterial carbon dioxide is modifiable and, as such, is a potential therapeutic target.
Patients experiencing sustained brain hypoxia require treatment in the Intensive Care Unit and have frequently associated poorer outcomes. Therefore a targeted treatment to improve blood flow could potentially improve clinical morbidity and mortality in this common condition and potentially reduce the costs associated with expensive sustained Intensive Care Admissions.
The TAME Cardiac Arrest Trial is a definitive phase III multi-centre randomised controlled trial in resuscitated cardiac arrest patients. Conducted by world-class investigators, this trial will determine whether targeted therapeutic mild hypercapnia (TTMH) during mechanical ventilation improves neurological outcome at 6 months compared to standard care (targeted normocapnia).
Supported by compelling preliminary data, significant improvements in patient outcomes are achievable with this proposed simple and cost free therapy. Recruiting 1,700 patients, 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 thousands of Irish and Australian citizens, transform clinical practice and yield major economic gains worldwide.