When Hell Freezes Over: Trials of Temperature Manipulation in Critical Illness

The bed is on fire

Two articles published online ahead of print in the NEJM last week deal with actual and attempted temperature manipulation to improve outcomes in critically ill patients.

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.

Enrolling Bad Patients After Good: Sunk Cost Bias and the Meta-Analytic Futility Stopping Rule

Four (relatively) large critical care randomized controlled trials were published early in the NEJM in the last week.  I was excited to blog on them, but then I realized they're all four old news, so there's nothing to blog about.  But alas, the fact that there is no news is the news.

In the last week, we "learned" that more transfusion is not helpful in septic shock, that EGDT (the ARISE trial) is not beneficial in sepsis, that simvastatin (HARP-2 trial) is not beneficial in ARDS, and that parental administration of nutrition is not superior to enteral administration in critical illness.  Any of that sound familiar?

I read the first two articles, then discovered the last two and I said to myself "I'm not reading these."  At first I felt bad about this decision, but then that I realized it is a rational one.  Here's why.