The aim of this substudy was to evaluate the effect of different temperature targets on the neurological outcome of patients who suffered out-of-hospital cardiac arrest (OHCA). The neurological outcome was assessed using the cerebral performance category (CPC) scale, which is a widely used tool to measure the level of brain function and disability after cardiac arrest . The CPC scale ranges from 1 to 5, where 1 indicates good recovery and 5 indicates brain death. A good neurological outcome was defined as having a CPC score of 1 or 2, while a poor neurological outcome was defined as having a CPC score of 3, 4 or 5. The CPC score was determined for each patient according to the protocol of the Targeted Temperature Management (TTM) trial, which was a multicenter randomized controlled trial that compared two temperature targets (33ÂC and 36ÂC) for post-cardiac arrest care .
The TTM trial was a landmark study that challenged the previous evidence on therapeutic hypothermia for cardiac arrest patients. The trial compared two different temperature targets, both intended to prevent fever, which is known to be harmful for the brain after ischemia. The trial found no difference in mortality or neurological outcome between the two groups, suggesting that the benefit of therapeutic hypothermia may not be related to the degree of cooling, but rather to the avoidance of hyperthermia .
However, the TTM trial had some limitations that may have affected its results. For example, the trial included patients with both shockable and non-shockable rhythms, who may have different responses to temperature management. The trial also used a relatively short duration of cooling (28 hours) and a rapid rewarming rate (0.5ÂC per hour), which may have reduced the potential neuroprotective effect of hypothermia. Moreover, the trial did not control for other aspects of post-cardiac arrest care, such as hemodynamic optimization, glucose control, and sedation, which may have confounded the outcome .
Therefore, further research is needed to determine the optimal temperature target and duration for cardiac arrest patients. A recent trial, called TTM2, compared targeted hypothermia at 33ÂC with targeted normothermia with early treatment of fever in 1900 patients with coma after out-of-hospital cardiac arrest of presumed cardiac or unknown cause. The trial found no difference in death or functional outcome at 6 months between the two groups, confirming the findings of the TTM trial . However, the TTM2 trial also had some limitations, such as a high rate of crossover between the groups, a low adherence to the temperature protocol, and a lack of blinding of the intervention. Moreover, the trial did not address the question of whether therapeutic hypothermia may be beneficial for specific subgroups of patients, such as those with longer duration of cardiac arrest or worse neurological status at admission .
One of the unresolved questions in the field of temperature management for cardiac arrest patients is whether there are specific subgroups of patients who may benefit more from therapeutic hypothermia than others. Previous trials have mainly focused on patients with shockable rhythms, such as ventricular fibrillation or pulseless ventricular tachycardia, who have a better prognosis than patients with non-shockable rhythms, such as asystole or pulseless electrical activity. However, some observational studies have suggested that therapeutic hypothermia may also improve the outcome of patients with non-shockable rhythms .
Another possible subgroup of interest is patients with longer duration of cardiac arrest or worse neurological status at admission. These patients have a higher risk of hypoxicâischemic brain injury and may benefit more from the neuroprotective effect of therapeutic hypothermia. However, the evidence for this hypothesis is limited and inconsistent. Some studies have found that therapeutic hypothermia may be more effective in patients with longer time to return of spontaneous circulation or lower Glasgow Coma Scale score , while others have found no interaction between these factors and temperature management .
Therefore, further trials are needed to identify the optimal candidates for therapeutic hypothermia among cardiac arrest patients. Such trials should be adequately powered and stratified to detect potential differences in outcome between subgroups based on initial rhythm, duration of cardiac arrest, neurological status at admission, and other relevant factors. Moreover, such trials should use standardized protocols for temperature management and other aspects of post-cardiac arrest care, and ensure adequate blinding and adherence to the intervention . 29c81ba772