Acetazolamide for the Management of Chronic Metabolic Alkalosis in Neonates and Infants

Tam, Benjamin; Chhay, Annie; Yen, Lilly; Tesoriero, Linda; Ramanathan, Rangasamy; Seri, István; Friedlich, Philippe

doi:10.1097/mjt.0b013e31825e792c

Cited by 9 publications

(7 citation statements)

References 14 publications

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“…Similar efficacy was noted in a neonatal ICU population of 90 patients with alkalosis in response to chronic respiratory insufficiency. 47 After 24 hours of therapy with ACTZ, the serum bicarbonate value decreased from 29.5 + 3.7 to 26.9 + 3.8 mEq/L, and the base excess decreased from 10.0 + 3.4 to 4.8 + 4.0 mEq/L. No significant differences in other electrolytes, blood urea nitrogen, and urine output were noted, except for an increased serum chloride and creatinine.…”

Section: Treatment Algorithm and Optionsmentioning

confidence: 86%

“…19,44,45 Clinical investigations have demonstrated the relative efficacy of ACTZ in correcting alkalosis in neonates, infants, and children with and without cardiac disease. [46][47][48][49] In a retrospective review of 34 pediatric patients (median age 0.25 years) who received at least three doses of ACTZ to treat metabolic alkalosis (pH !7.45 and bicarbonate !26 mEq/L), there was a change in the preversus the post-ACTZ pH and serum bicarbonate from 7.51 + 0.05 to 7.37 + 0.05 and 39.4 + 6.1 to 31.4 + 7.5 mEq/L. Acetazolamide dosing averaged 5 mg/kg/dose and was administered every eight hours (70% of the patients).…”

Section: Treatment Algorithm and Optionsmentioning

confidence: 99%

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Metabolic Alkalosis in the Pediatric Patient: Treatment Options in the Pediatric ICU or Pediatric Cardiothoracic ICU Setting

Tobias

2020

World J Pediatr Congenit Heart Surg

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Metabolic alkalosis is characterized by the primary elevation of the serum bicarbonate concentration with a normal or elevated partial pressure of carbon dioxide. Although there may be several potential etiologies in the critically ill patient in the pediatric or cardiothoracic intensive care unit, metabolic alkalosis most commonly results from diuretic therapy with chloride loss. In most cases, the etiology can be determined by a review of the patient’s history and medication record. Although generally innocuous with limited impact on physiologic function, metabolic alkalosis may impair central control of ventilation, especially when weaning from mechanical ventilation. The following manuscript presents the normal homeostatic mechanisms that control pH, reviews the etiology of metabolic alkalosis, and outlines the differential diagnosis. Options and alternatives for treatment including pharmacologic interventions are presented with a focus on these conditions as they pertain to the patient in the pediatric or cardiac intensive care unit.

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Section: Treatment Algorithm and Optionsmentioning

confidence: 86%

Section: Treatment Algorithm and Optionsmentioning

confidence: 99%

Metabolic Alkalosis in the Pediatric Patient: Treatment Options in the Pediatric ICU or Pediatric Cardiothoracic ICU Setting

Tobias

2020

World J Pediatr Congenit Heart Surg

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“…The decrease in brain pH associated with CA inhibition was paralleled by an increase in blood P co 2 , with no change in blood HCO 3 − concentration for a period of 2–4 h. Thus the main antiseizure mode of action of the CAIs in the present study is based on the respiratory acidosis resulting from the inhibition of blood‐borne and vascular CA isoforms. The wide use of AZA in the neonatal and pediatric populations 31–33 suggests a high safety level of this drug for repurposing it for the treatment of neonatal seizures as an add‐on to PhB, and perhaps as an adjunct in future clinical trials with some other antiseizure drug.…”

Section: Introductionmentioning

confidence: 99%

Carbonic anhydrase inhibitors suppress seizures in a rat model of birth asphyxia

et al. 2021

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Objective Seizures are common in neonates recovering from birth asphyxia but there is general consensus that current pharmacotherapy is suboptimal and that novel antiseizure drugs are needed. We recently showed in a rat model of birth asphyxia that seizures are triggered by the post‐asphyxia recovery of brain pH. Here our aim was to investigate whether carbonic anhydrase inhibitors (CAIs), which induce systemic acidosis, block the post‐asphyxia seizures. Methods The CAIs acetazolamide (AZA), benzolamide (BZA), and ethoxzolamide (EZA) were administered intraperitoneally or intravenously to 11‐day‐old rats exposed to intermittent asphyxia (30 min; three 7+3 min cycles of 9% and 5% O2 at 20% CO2). Electrode measurements of intracortical pH, Po2, and local field potentials (LFPs) were made under urethane anesthesia. Convulsive seizures and blood acid‐base parameters were examined in freely behaving animals. Results The three CAIs decreased brain pH by 0.14–0.17 pH units and suppressed electrographic post‐asphyxia seizures. AZA, BZA, and EZA differ greatly in their lipid solubility (EZA > AZA > BZA) and pharmacokinetics. However, there were only minor differences in the delay (range 0.8–3.7 min) from intraperitoneal application to their action on brain pH. The CAIs induced a modest post‐asphyxia elevation of brain Po2 that had no effect on LFP activity. AZA was tested in freely behaving rats, in which it induced a respiratory acidosis and decreased the incidence of convulsive seizures from 9 of 20 to 2 of 17 animals. Significance AZA, BZA, and EZA effectively block post‐asphyxia seizures. Despite the differences in their pharmacokinetics, they had similar effects on brain pH, which indicates that their antiseizure mode of action was based on respiratory (hypercapnic) acidosis resulting from inhibition of blood‐borne and extracellular vascular carbonic anhydrases. AZA has been used for several indications in neonates, suggesting that it can be safely repurposed for the treatment of neonatal seizures as an add‐on to the current treatment regimen.

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“…Diuretic use alters electrolyte balances, potentially leading to hypochloremia and alkalosis. 1 Metabolic alkalosis can have further untoward effects, including neuromuscular and cardiovascular complications and compensatory hypoventilation due to hypercarbia. As a result, metabolic alkalosis may increase the duration, or time to wean off, of mechanical ventilation.…”

Section: Introductionmentioning

confidence: 99%

“…2 It has also been shown that acetazolamide can resolve metabolic alkalosis, while increasing serum chloride levels, in neonates and infants with chronic respiratory insufficiency. 1 The evidence is controversial regarding acetazolamide's utility in pediatric cardiac patients. 2,5 Other options for correcting hypochloremia include sodium chloride, potassium chloride, 6 and ammonium chloride, 7 but these are not without ramifications for other electrolytes.…”

Section: Introductionmentioning

confidence: 99%

Use of Arginine Hydrochloride in the Treatment of Metabolic Alkalosis or Hypochloremia in Pediatric Patients

Sierra¹,

Hernandez²,

Parbuoni³

2018

The Journal of Pediatric Pharmacology and Therapeutics

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Dosing of arginine for treatment of hypochloremia or metabolic alkalosis is laborious and has inherent variability in dose selection. The primary objective of this study was to determine the efficacy of arginine in the treatment of metabolic alkalosis and hypochloremia. Secondary objectives were to determine an optimal dose, route, and frequency for arginine administration in the treatment of these conditions. METHODS This single center, retrospective, descriptive study was conducted in children who received arginine for treatment of hypochloremia or metabolic alkalosis. Treatment success was assessed by measuring serum chloride and bicarbonate concentrations after arginine administration. RESULTS Of the 464 orders analyzed, 177 met inclusion criteria in 82 unique patients. Fifty percent (n = 81) of arginine administrations used to manage hypochloremia saw normalization of abnormal chloride levels, and 83% (n = 62) of arginine administrations used to treat metabolic alkalosis saw normalization of abnormal bicarbonate levels. Patients who received arginine to resolve hypochloremia were statistically significantly more likely to have their hypochloremia resolve if they used alternative dosing methods compared to established dosing methods (76 vs. 5, p = 0.001). However, this relationship was not seen for patients with metabolic alkalosis (11 vs. 51, p = 1.000). The median percentage of calculated daily dose of arginine needed for resolution of hypochloremia was 59% and was 35% for metabolic alkalosis. CONCLUSIONS Arginine is effective to improve metabolic alkalosis and hypochloremia. Established dosing methods are not more effective than other methods in resolving metabolic alkalosis or hypochloremia. Further prospective studies are warranted to validate these results.

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Acetazolamide for the Management of Chronic Metabolic Alkalosis in Neonates and Infants

Cited by 9 publications

References 14 publications

Metabolic Alkalosis in the Pediatric Patient: Treatment Options in the Pediatric ICU or Pediatric Cardiothoracic ICU Setting

Metabolic Alkalosis in the Pediatric Patient: Treatment Options in the Pediatric ICU or Pediatric Cardiothoracic ICU Setting

Carbonic anhydrase inhibitors suppress seizures in a rat model of birth asphyxia

Use of Arginine Hydrochloride in the Treatment of Metabolic Alkalosis or Hypochloremia in Pediatric Patients

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