Lowering body temperature during the first hours after cardiac arrest reduces neurologic injury by disrupting pathological cellular events and cascades that might lead to secondary brain injury. Randomized trials demonstrated that therapeutic hypothermia early after cardiac arrest reduces mortality and improves outcome. Based on preliminary results, it was postulated that a shorter delay to target temperature would further improved outcome. However, those early results were not verified in following randomized trials. Thus, the question if time or delay to therapeutic hypothermia matter in patients resuscitated from cardiac arrest...
Well, it seems unlikely that delay to treatment would be beneficial. On the other hand, it may be that there is an important time period (say 36 hours) where people who are cooled later are still cool (say if you have a 24 hour protocol), than people who are cooled early. My suspicion is that is the explanation for failure to see an effect of lower time to target (that lower time to target, coupled with longer overall cooling would actually be better),
I wonder how many of these studies control for patient who were relatively hypothemic at the time ROSC was achieved. We are reviewing our experience with abotu 200 post cardiac arrest hypothermia patients and in looking at time to acheive hypothermia target we are finding the baseline temp is of course a confounding factor. Being hypothermic at time ROSC was acheived might be considered protective in some situations in which cooling was achieved very rapidly such as the classice example of near drowning, but in garden variety cardiac arret reflects longer down time and may be confounder.
I totally agree that so far we do not have good data about faster/early is better. Nevertheless especially for device advertisement this a key point. Often the advantage of endovascular catethers is supposed to be faster cooling compared to external cooling forgetting about the risk of access site bleeding or infections. In our hypothermia patients we found no postive correlation with starting temperature or time to target temp (32-34 °C). Maybe we need another multicentre study to get this clear.
Dear Michael, dear Ingo,
thank you both very much for sharing your experience and your preliminary data. It seems more than important to perform prospective multicenter trials in this context. Regarding the possible confounders (e.g., baseline temperature, length of CPR, ...) it would be interesting to know how your results (Michael) are influenced after adjusting the multivariable analysis.
Once again - thank you for your contributions and best regards
Raoul
This is a little out of my field of expertise, but don't forget that in ischemia different parts of the brain are differently affected by hypoxia partly due to their different metabolic rates. I would therefore expect that faster cooling would be most beneficial to the areas that typically suffer the most from ischemia, and if there are any drawbacks from faster cooling, the benefit / risk ratio might be worse in the areas that are not quickly harmed by ischemia.
This is an important point from Daniel - thank you. This is also mirrored by preliminary data from a study at the JHH where "post mortem" neuropathologic exams of ICU patients who died from different non-neurologic critical illnesses revealed that especially cortical and hippocampal areas are susceptible; however - independent from the duration of marked arterial hypotension (MAP
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