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Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in intensive care unit patients

Introduction

Metabolic alkalosis is a well-known acid–base derangement in the ICU. Treatment with the carbonic anhydrase inhibitor acetazolamide is indicated in selected cases. According to the quantitative physicochemical approach described by Stewart, correction of serum pH due to carbonic anhydrase inhibition in the proximal tubule cannot be explained by excretion of bicarbonate. pH is exclusively mediated by three independent variables: pCO2, total concentration of weak acids, and the difference between dissociated anions and cations (SID). We therefore studied the mechanism of action of acetazolamide in critically ill patients with a metabolic alkalosis according to the Stewart approach.

Methods

The study was approved by the local ethics committee and the need for informed consent waived. Fifteen consecutive ICU patients with metabolic alkalosis (pH > 7.48 and HCO3 > 28 mmol/l) were treated with a single administration of 500 mg acetazolamide intravenously. Serum levels of strong ions, creatinine, lactate, weak acids, pH and pCO2 were measured at 0, 12, 24, 48 and 72 hours. Main strong ions of the urine (sodium, chloride and potassium) and pH were measured at 0, 3, 6, 12, 24, 48 and 72 hours. Strong ion difference (SID), strong ion gap (SIG) and the Na–Cl effect were calculated. Effects of acetazolamide were analyzed by comparing baseline variables and the time-dependent changes by one-way analysis of variance for repeated measures.

Results

Eighty-seven percent of patients were mechanically ventilated and 47% were treated with diuretics. Ventilator settings and diuretic dose were not changed during the study period. Mean APACHE II score was 21 (range 12–30) and hospital mortality was 20% (SMR 0.57). Correction of serum pH (7.49 ± 0.01 to 7.46 ± 0.01; P = 0.001) was maximal at 24 hours and sustained during the observation period. The parallel decrease in pCO2 was not significant (5.7 ± 0.2 to 5.3 ± 0.2 kPa, P = 0.08). Also, there was no significant change in the total concentration of weak acids. Serum SID significantly decreased during the observation period (41.5 ± 1.3 to 38.0 ± 1.0 mEq/l, P = 0.03) due to an increase in serum chloride (105 ± 1.2 to 110 ± 1.2 mmol/l, P < 0.0001). There was a very strong relation between the serum SID and the Na–Cl effect (R2 = 0.99, P = < 0.001) The decrease in serum SID was explained by a significant increase in the urinary excretion of sodium without chloride in the first 24 hours (urinary [Na]/[Cl] 1.3 ± 0.3 to 2.5 ± 0.5, P = 0.02).

Conclusions

A single dose of acetazolamide effectively corrects metabolic alkalosis in critically ill patients by decreasing the serum SID. This effect is completely explained by the increased renal excretion ratio of sodium/chloride, resulting in an increase in serum chloride.

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Pickkers, P., Moviat, M. & Van der Hoeven, H. Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in intensive care unit patients. Crit Care 9, P411 (2005). https://doi.org/10.1186/cc3474

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Keywords

  • Carbonic Anhydrase
  • Intensive Care Unit Patient
  • Excretion Ratio
  • Weak Acid
  • Acetazolamide