Diamox Results in Urine: General and Specific Lessons from the DIABOLO Acetazolamide Trial

The trial of acetazolamide to reduce duration of mechanical ventilation in COPD patients was published in JAMA this week.  I will use this trial to discuss some general principles about RCTs and make some comments specific to this trial.

My arguable but strong prior belief, before I even read the trial, is that Diamox (acetazolamide) is ineffectual in acute and chronic respiratory failure, or that it is harmful.  Its use is predicated on a "normalization fallacy" which guides practitioners to try attempt to achieve euboxia (normal numbers).  In chronic respiratory acidosis, the kidneys conserve bicarbonate to maintain normal pH.  There was a patient we saw at OSU in about 2008 who had severe COPD with a PaCO2 in the 70s and chronic renal failure with a bicarbonate under 20.  A well-intentioned but misguided resident checked an ABG and the patient's pH was on the order of 7.1.  We (the pulmonary service) were called to evaluate the patient for MICU transfer and intubation, and when we arrived we found him sitting at the bedside comfortably eating breakfast.  So it would appear that if the kidneys can't conserve enough bicarbonate to maintain normal pH, patients can get along with acidosis, but obviously evolution has created systems to maintain normal pH.  Why you would think that interfering with this highly conserved system to increase minute ventilation in a COPD patient you are trying to wean is beyond the reach of my imagination.  It just makes no sense.

This brings us to a major problem with a sizable proportion of RCTs that I read:  the background/introduction provides woefully insufficient justification for the hypothesis that the RCT seeks to test.  In the background of this paper, we are sent to references 4-14.  Here is a summary of each:

4.)  A review of metabolic alkalosis in a general population of critically ill patients
5.)  An RCT of acetazolamide for weaning COPD patients showing that it doesn't work
6.)  Incidence of alkalosis in hospitalized patients in 1980
7.)  A 1983 translational study to delineate the effect of acetazolamide on acid base parameters in 10 paitnets
8.)  A 1982 study of hemodynamic parameters after acetazolamide administration in 12 patients
9.)  A study of metabolic and acid base parameters in 14 patients with cystic fibrosis 

10.) A retrospective epidemiological descriptive study of serum bicarbonate in a large cohort of critically ill patients

11.)  A study of acetazolamide in anesthetized cats

12 - 14).  Commentary and pharmacodynamic studies of acetazolamide by the authors of the current study