|The bed is on fire|
The Eurotherm3235 trial was stopped early because of concerns of harm or futility. This trial enrolled patients with traumatic brain injury (TBI) and elevated intracranial pressure (ICP) and randomized them to induced hypothermia (which reduces ICP) versus standard care. There was a suggestion of worse outcomes in the hypothermia group. I know that the idea that we can help the brain with the simple maneuver of lowering body temperature has great appeal and what some would call "biological plausibility" a term that I henceforth forsake and strike from my vocabulary. You can rationalize the effect of an intervention any way you want using theoretical biological reasoning. So from now on I'm not going to speak of biological plausibility, I will call it biological rationalizing. A more robust principle, as I have claimed before, is biological precedent - that is, this or that pathway has been successfully manipulated in a similar way in the past. It is reasonable to believe that interfering with LDL metabolism will improve cardiovascular outcomes because of decades of trials of statins (though agents used to manipulate this pathway are not all created equal). It is reasonable to believe that intervening with platelet aggregation will improve outcomes from cardiovascular disease because of decades of trials of aspirin and plavix and others. It is reasonable to doubt that manipulation of body temperature will improve any outcome because there is no unequivocal precedent for this, save for warming people with hypothermia from exposure - which basically amounts to treating the known cause of their ailment. This is one causal pathway that we understand beyond a reasonable doubt. If you get exposure, you freeze to death. If we find you still alive and warm you, you may well survive.