|Year : 2015 | Volume
| Issue : 1 | Page : 1-2
What is new in critical illness and injury science? Acetazolamide in decompensated respiratory failure!
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
|Date of Web Publication||2-Mar-2015|
Department of Pathophysiology and Transplantation, University of Milan, Via Festa del Perdono 3, Milan
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Colombo J. What is new in critical illness and injury science? Acetazolamide in decompensated respiratory failure!. Int J Crit Illn Inj Sci 2015;5:1-2
|How to cite this URL:|
Colombo J. What is new in critical illness and injury science? Acetazolamide in decompensated respiratory failure!. Int J Crit Illn Inj Sci [serial online] 2015 [cited 2020 Jan 20];5:1-2. Available from: http://www.ijciis.org/text.asp?2015/5/1/1/152293
Invasively ventilated patients with chronic obstructive pulmonary disease (COPD) are at a high risk of prolonged mechanical ventilation. ,
Age, severity of illness, associated diseases such as pneumonia, cardiac dysfunction, and metabolic alkalosis (MA) are associated with persistent weaning failure. 
Situations of chronic respiratory acidosis are usually associated with MA. It is due to the metabolic compensation of respiratory acidosis (there is a linear relationship between increasing bicarbonate and progressive increase in PaCO2, with a slope of about 0.7) and to treatments such as diuretics, steroids, nasogastric suctioning, or low-salt diets.
The raised bicarbonate level buffers the effect of the raised arterial carbon dioxide level (PaCO2), reducing the drive to breathe associated with the respiratory acidosis and causing alveolar hypoventilation. 
Furthermore, MA itself is associated with impairment of hypoxic pulmonary vasoconstriction, alterations in oxyhemoglobin dissociation, reduced cardiac output, cardiac dysrhythmias, and increased mortality. 
From a pathophysiological point of view, restoring the physiological pH or even inducing a mild metabolic acidosis should cause a favorable shifts in the oxygen-dissociation curve and a stimulation of chemoreceptors, which in turn induces an increase in minute ventilation. 
Acetazolamide (ACET), a nonspecific carbonic anhydrase (CA) inhibitor, is one of the drugs employed to reverse MA. 
In this issue, we publish the results of a case-control study designed to evaluate the impact of ACET in COPD exacerbation requiring IMV.
ACET promotes renal excretion of bicarbonate along with strong cations by inhibition of CA IV in the proximal tubules. The mild metabolic acidosis that results can be explained both by the Henderson-Hasselbalch equation (the loss of bicarbonate determines the fall in pH) and by the physicochemical approach described by Stewart (the decrease in SID, due to a renal excretion of sodium without chloride, resulting in a relative increase in serum chloride, determines the decrease in pH)  ACET acts also on CA II, which plays a role in regulating gas exchange in the lung and in the erythrocyte and might modulate the activity of slowly adapting pulmonary stretch receptors (SARs), which seem to play a role in the control of respiratory rate and tidal volume. 
In last years, ACET was proposed as an adjunctive treatment for ventilatory failure due to COPD.
250-500 mg of ACET induce an increase in minute ventilation by 10% to 20% in healthy subjects and an increase in oxygen saturation of hemoglobin by 3% to 6% in subjects with hypoxemia. ,
The study published in this issue concluded that 500 mg per day of ACET reverses MA, reduces PaCO 2 but has no effects on PaO 2 /FiO 2 ratio and the duration of mechanical ventilation, ICU mortality and ICU staying.
These results match with previously published clinical trials. ,, Currently, ACET given to patients with both COPD and MA appears to be only a cosmetic.
We can speculate on why ACET is, for the moment, only a cosmetic and not a therapy.
First of all, the tissue compartmentalization of CA isoforms and the low selectivity of ACET may explain, in part, the complexity of the effect of the drug in patients with COPD and, in turn, might explain why the efficacy of ACET is so moderate in the critically ill patient with COPD. Another possible explanation is that the usually employed doses of the drug are insufficient to improve the clinical situation.
An alternative reason could be that the factors other than MA are more important during discontinuation from mechanical ventilation.
From the literature, we can say with certainty that ACET is well tolerated and has few side effects. This must be the starting point for testing the efficacy of higher dose ACET in COPD and to develop and test drugs modulating specific CA isoenzimes.
The stakes are high and the physiopathological prerequisites for success are solid: Based on what we know, we need to create new paths.
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