Cardiac arrest is a common and catastrophic event with substantial human and financial costs. It is well established that cardiac arrest leads to brain injury. However, what is not widely appreciated is that, after circulation has been restored, cerebral (brain) hypoperfusion (inadequate blood supply) continues. Ongoing cerebral vasoconstriction (blood vessel constriction) and cerebral hypoxia (inadequate oxygen) has been demonstrated using imaging and metabolic technologies including positron emission tomography, ultrasound, jugular bulb oxygen saturation and cerebral oximetry. A likely mechanism responsible for sustained early cerebral hypoperfusion relates to impaired cerebrovascular autoregulation which is the ability of the brain to maintain its own perfusion. 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. PaCO2 is the major determinant of cerebral blood flow and an increased PaCO2 (hypercapnia) markedly increases cerebral blood flow. Arterial carbon dioxide is modifiable and, as such, is a potential therapeutic target. The TAME Cardiac Arrest Trial is a 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 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 simple and cost-free therapy. Recruiting 1,700 patients, for multiple sites in many countries, this will be one of the largest trial ever conducted involving resuscitated cardiac arrest patients admitted to ICU. If the TAME Cardiac Arrest Trial confirms that TTMH is effective, its findings will improve the lives of many patients, transform clinical practice and yield major economic gains worldwide.
The primary objective of this study is to determine whether targeted therapeutic mild hypercapnia (TTMH) improves neurological outcome at 6 months compared to standard care (targeted normocapnia) (TN).
Professor Glenn Eastwood