Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation

Faisy, Christophe; Mokline, A; Sanchez, Olivier; Tadié, Jean‐Marc; Fagon, Jean-Yves

doi:10.1007/s00134-010-1795-7

Cited by 43 publications

(42 citation statements)

References 12 publications

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“…During the weaning process, β 2 -agonists or furosemide was administered by attending physicians as indicated. In our ICU, the criteria for extubation were also standardized in a written protocol detailed elsewhere [10]. …”

Section: Methodsmentioning

confidence: 99%

“…It has been established that a single 500-mg daily dose of ACET reverses metabolic alkalosis over 72 hours in intubated patients with COPD or asthma as effectively as multiple doses of 250 mg [9]. However, a recent study has shown that ACET administration at a daily dose of 500 mg during the weaning period of COPD patients with mixed or pure metabolic alkalosis only moderately diminishes serum HCO 3 - levels, without changing either partial pressure of carbon dioxide (PaCO 2 ) levels or minute ventilation [10]. The lack of effectiveness of ACET on respiratory mechanics could be due to alterations in ACET pharmacodynamics [10].…”

Section: Introductionmentioning

confidence: 99%

“…However, a recent study has shown that ACET administration at a daily dose of 500 mg during the weaning period of COPD patients with mixed or pure metabolic alkalosis only moderately diminishes serum HCO 3 - levels, without changing either partial pressure of carbon dioxide (PaCO 2 ) levels or minute ventilation [10]. The lack of effectiveness of ACET on respiratory mechanics could be due to alterations in ACET pharmacodynamics [10]. Indeed, ACET pharmacodynamics in ICU patients has received little attention, especially in mechanically ventilated COPD patients.…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

2011

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IntroductionAcetazolamide is commonly given to chronic obstructive pulmonary disease (COPD) patients with metabolic alkalosis. Little is known of the pharmacodynamics of acetazolamide in the critically ill. We undertook the pharmacodynamic modeling of bicarbonate response to acetazolamide in COPD patients under mechanical ventilation.MethodsThis observational, retrospective study included 68 invasively ventilated COPD patients who received one or multiple doses of 250 or 500 mg of acetazolamide during the weaning period. Among the 68 investigated patients, 207 time-serum bicarbonate observations were available for analysis. Population pharmacodynamics was modeled using a nonlinear mixedeffect model. The main covariates of interest were baseline demographic data, Simplified Acute Physiology Score II (SAPS II) at ICU admission, cause of respiratory failure, co-prescription of drugs interfering with the acid-base equilibrium, and serum concentrations of protein, creatinin, potassium and chloride. The effect of acetazolamide on serum bicarbonate levels at different doses and in different clinical conditions was subsequently simulated in silico.ResultsThe main covariates interacting with acetazolamide pharmacodynamics were SAPS II at ICU admission (P = 0.01), serum chloride (P < 0.001) and concomitant administration of corticosteroids (P = 0.02). Co-administration of furosemide significantly decreased bicarbonate elimination. Acetazolamide induced a decrease in serum bicarbonate with a dose-response relationship. The amount of acetazolamide inducing 50% of the putative maximum effect was 117 ± 21 mg. According to our model, an acetazolamide dosage > 500 mg twice daily is required to reduce serum bicarbonate concentrations > 5 mmol/L in the presence of high serum chloride levels or coadministration of systemic corticosteroids or furosemide.ConclusionsThis study identified several covariates that influenced acetazolamide pharmacodynamics and could allow a better individualization of acetazolamide dosing when treating COPD patients with metabolic alkalosis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

2011

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“…For example, Faisy et al found that a single intravenous dose of acetazolamide (500 mg daily) effectively reduced serum bicarbonate values in patients with metabolic alkalosis, but did not improve PaCO 2 or respiratory parameters such that COPD patients could be more rapidly weaned from mechanical ventilation. 7 Mazur et al found that a single 500-mg intravenous dose of acetazolamide was as effective as multiple 250 mg doses in reversing non-chlorideresponsive metabolic alkaloses in mechanically ventilated asthma/ COPD patients, but they did not specifically assess clinical end points. 8 This latter study argues for less aggressive treatment with acetazolamide, which, in turn, would lessen the occurrence of electrolyte disorders such as hyperchloremic, hypokalemic metabolic alkalosis.…”

Section: Metabolic Alkalosismentioning

confidence: 98%

Acetazolamide

Kassamali

Sica

2011

Cardiology in Review

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Acetazolamide is the only carbonic anhydrase inhibitor with significant diuretic effects. It is readily absorbed and undergoes renal elimination by tubular secretion. Its administration is ordinarily marked by a brisk alkaline diuresis. Although carbonic anhydrase inhibitors are proximal tubular diuretics (where the bulk of sodium re-absorption occurs), their net diuretic effect is modest in that sodium re-absorption in more distal nephron segments offsets proximal sodium losses. Acetazolamide use is limited by both its transient action and the development of metabolic acidosis with extended administration. Acetazolamide can, however, correct the significant metabolic alkalosis which occasionally occurs with loop diuretic therapy.

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“…In summary, we found that this recent study (1), confirms the results of two retrospective, case-control studies (3,7) and one randomized clinical trial (8) published on the same subject. The conclusions of all these studies (1,3,7,8) were in severe exacerbation of COPD requiring intensive care admission and invasive MV, metabolic alkalosis occurs frequently in this group of patients who frequently receive therapies for cardiac and respiratory failures (steroids, diuretics, etc.). Moreover, these studies suggest that systemic ACET therapy in this specific condition is not helpful to reduce the duration of MV and to make the weaning process easier.…”

mentioning

confidence: 99%

Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease: still far from the truth?

Bahloul¹,

Ammar²,

Bouattour³

et al. 2017

J. Thorac. Dis.

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In this study, Rialp Cervera et al.(1) have randomly assigned patients with chronic obstructive pulmonary disease (COPD) or obesity hypoventilation syndrome (OHS) with acute respiratory failure requiring mechanical ventilation (MV) <72 h to receive either acetazolamide 500 mg or placebo. All patients had initial bicarbonate >28 mmol/L and pH >7.35. Test-treatment, ACTZ 500 mg or placebo, was daily administered if pH >7.35 and bicarbonate >26 mmol/L. Clinical, respiratory and laboratory parameters were recorded on a daily basis.This was a multicenter, randomized, placebo-controlled, phase III, double-blind study held in seven intensive care units in Spain. Patients with COPD or OHS, requiring invasive MV due to acute respiratory failure for less than 72 h and who showed metabolic alkalosis with pH >7.35 and with plasmatic bicarbonate >28 mmol/L, while being on invasive MV, were consecutively included from November 2011 to February 2014. Forty seven patients (36 men) were randomized as ACTZ (+) or placebo: 23 patients in placebo group, and 24 in ACTZ (+) group. There were no significant differences between groups in comorbidities, baseline characteristics or arterial blood gases at inclusion. At inclusion, SOFA score, proportion of patients with noninvasive ventilation (NIV) failure before inclusion, reason of invasive MV, laboratory serum tests, blood gas analysis and respiratory parameters did not show any significant differences between groups.This study (1) showed no significant decreases in the duration of MV and weaning, or in the length of ICU and hospital stay with acetazolamide treatment compared with placebo in intubated patients with COPD or OHS and metabolic alkalosis. Moreover, patients treated with acetazolamide showed a significant reduction in bicarbonate concentration and PaCO 2 values at discontinuation of MV, with 33% of them having recovered from their metabolic alkalosis, whereas no patient in the placebo group did so. Moreover, respiratory rate and minute volume did not show any significant differences throughout the MV period although minute volume tended to increase over time in the acetazolamide group [minute volume 9.7 (8.9-10.4) vs. 10.6 (9.2-12.0) L/min, P=0.26].In conclusion, this study showed that in severe exacerbation of COPD or OHS requiring intensive care admission and invasive MV, despite the fact that acetazolamide is used to reverse metabolic alkalosis, this therapy does not help reduce the duration of MV and/or make the weaning process easier.Nevertheless, this study-as mentioned by authorssuffers from many limitations. First, a sample size of 98 patients was estimated to have a power of 80% with an alpha error of 5% to detect a 3-day difference between groups in the duration of MV. However, the study was stopped prematurely due to slow patient recruitment. In fact, only 47 patients were included in the study, 23 patients in the placebo group and 24 in the acetazolamide one. Consequently, this study did not detect any significant J Thorac Dis 2017;9(6):1393-1395 jtd.amegroups....

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Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation

Abstract: ACET used at the dosage of 500 mg per day reduces metabolic alkalosis but has no benefit in terms of improving PaCO(2) or respiratory parameters in weaning COPD patients from mechanical ventilation.

Cited by 43 publications

References 12 publications

Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

Acetazolamide

Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease: still far from the truth?

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