Acetazolamide: a second wind for a respiratory stimulant in the intensive care unit?
34
Citation
54
Reference
10
Related Paper
Citation Trend
Abstract:
Patients with chronic obstructive pulmonary disease (COPD) are affected by episodes of respiratory exacerbations, some of which can be severe and may necessitate respiratory support. Prolonged invasive mechanical ventilation is associated with increased mortality rates. Persistent failure to discontinue invasive mechanical ventilation is a major issue in patients with COPD. Pure or mixed metabolic alkalosis is a common finding in the intensive care unit (ICU) and is associated with a worse outcome. In patients with COPD, the condition is called post-hypercapnic alkalosis and is a complication of mechanical ventilation. Reversal of metabolic alkalosis may facilitate weaning from mechanical ventilation of patients with COPD. Acetazolamide, a non-specific carbonic anhydrase inhibitor, is one of the drugs employed in the ICU to reverse metabolic alkalosis. The drug is relatively safe, undesirable effects being rare. The compartmentalization of the different isoforms of the carbonic anhydrase enzyme may, in part, explain the lack of evidence of the efficacy of acetazolamide as a respiratory stimulant. Recent findings suggest that the usually employed doses of acetazolamide in the ICU may be insufficient to significantly improve respiratory parameters in mechanically ventilated patients with COPD. Randomized controlled trials using adequate doses of acetazolamide are required to address this issue.Keywords:
Acetazolamide
Carbonic anhydrase inhibitor
Respiratory alkalosis
Alkalosis
The development of blood ionic changes could be precipitated in acid-base disorder and subsequent treatment. As technology for detecting circulating ionized Mg²? (the most interesting form with respect to physiological and biological properties) is now available in veterinary clinical medicine. This present study investigated the changes of whole blood ionized Mg²? correlated with acute metabolic and respiratory alkalosis in rodent model. Metabolic alkalosis was induced by intravenous infusion with NaHCO₃ and mechanical hyperventilation was applied for respiratory alkalosis. We founded that the blood ionized Mg²? could be reversibly decreased by the NaHCO₃-induced acute metabolic alkalosis but irreversibly increased by the mechanical hyperventilation-induced respiratory acidosis and respiratory acidosis. We suggested that the potential change in blood suggested that the potential change in blood ionized Mg²? should be counted in treatment of acid-base disorders.
Respiratory alkalosis
Respiratory acidosis
Alkalosis
Acid–base homeostasis
Cite
Citations (6)
Acetazolamide is an option for hypochloremic metabolic alkalosis, but there are limited reports in children.To describe the acetazolamide regimen and outcomes in critically ill children with metabolic alkalosis.This was a descriptive, retrospective study of patients <18 years of age who received ≥3 doses of acetazolamide for metabolic alkalosis (ie, pH > 7.45 and bicarbonate [HCO3] > 26 mEq/L). Patients receiving other treatments for metabolic alkalosis within 24 hours of acetazolamide were excluded. The primary objective was to identify the mean dose and duration of acetazolamide. Secondary objectives were to determine the number of patients with treatment success (ie, serum HCO3 22-26 mEq/L) and occurrence of adverse events.Thirty-four patients were included for analysis, the median age was 0.25 years (range = 0.05-12 years). The acetazolamide regimen included a mean dose of 4.98 ± 1.14 mg/kg for a mean number of 6.1 ± 5.3 (range = 3-24) doses. The majority (70.6%) received acetazolamide every 8 hours. Treatment success was achieved in 10 (29.4%) patients. Statistically significant differences were noted between the pre-acetazolamide and post-acetazolamide pH and HCO3, 7.51 ± 0.05 versus 7.37 ± 0.05 (P < .001) and 39.4 ± 6.1 mEq/L versus 31.4 ± 7.5 mEq/L (P < .001), respectively.This is the first study to evaluate acetazolamide dosing for metabolic alkalosis in children with and without cardiac disease. Acetazolamide treatment resulted in improved HCO3, but the majority of patients did not achieve our definition of treatment success. Future studies should elucidate the optimal acetazolamide regimen.
Acetazolamide
Alkalosis
Cite
Citations (15)
We hypothesized that inhibition of carbonic anhydrase in the central nervous system by acetazolamide should limit the rise in cisternal cerebrospinal fluid (CSF) [HCO3-] observed in metabolic alkalosis. To test this hypothesis, isosmotic isonatremic metabolic alkalosis was produced in two groups of anesthetized, paralyzed, and mechanically ventilated dogs (8 in each group). Group II animals received 50 mg/kg of acetazolamide intravenously 1 h before induction of metabolic alkalosis of 5-h duration. Renal effects of acetazolamide were eliminated by ligation of renal pedicles. In both groups cisternal CSF [Na+] remained relatively constant during metabolic alkalosis. In group I CSF [Cl-] decreased 3.6 and 8.2 meq/l, respectively, 2.5 and 5 h after induction of metabolic alkalosis. Respective increments in CSF [HCO3-] were 3.4 and 6.0 meq/l. In acetazolamide-treated dogs, during metabolic alkalosis, increments in CSF [HCO3-] (4.8 and 7.2 meq/l, respectively, at 2.5 and 5 h) and decrements in CSF [Cl-] (9.1 and 13.3 meq/l) were greater than those observed in group I. We conclude that, in dogs with metabolic alkalosis and bilateral ligation of renal pedicles, acetazolamide impairs CSF regulation of HCO3- and Cl- ions; acetazolamide not only failed to impede HCO3- rise but actually appeared to increase it. The mechanisms for these observations are discussed.
Acetazolamide
Alkalosis
Respiratory alkalosis
Cite
Citations (11)
Acetazolamide, a carbonic anhydrase (CA) inhibitor, was used to normalize metabolic alkalemia. A dosage of acetazolamide for normalizing metabolic alkalemia has not yet been experimentally determined. The dosage of acetazolamide for this purpose is experimentally calculated in this paper. The correlation between various concentration of acetazolamide mixed with blood and the base excess (BE) levels in blood at the start of normalizing metabolic alkalosis was studied in vitro. The change rate of the BE level was calculated from BE levels noted before and after tonometry of the blood with and without acetazolamide. A dosage of acetazolamide which can cause the change rate of the BE level to decrease is considered to be an effective dosage. Metabolic alkalosis in vitro was produced by adding bicarbonate into the blood. An effective dosage of acetazolamide for metabolic alkalemia of which the BE range was from 0 to + 30 mEq/liter was calculated. CA activities in the kidney and the blood of dogs administered acetazolamide were examined. The effective dosage of acetazolamide obtained from in vitro experiments inhibited the CA activities not only in the blood but also in the kidneys. An effective dosage of acetazolamide to normalize a BE of + 10 mEq/liter in vitro was converted into about 7-12 mg/kg in vivo. This dosage inhibited the red blood cell carbonic anhydrase (RCA) activity to 20-40%, whereas the normal physiological variation range is 25%. An effective dosage of acetazolamide in the blood did not proportionally increase with an increase of HCO3- during severe alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetazolamide
Alkalosis
Acid–base homeostasis
Carbonic anhydrase inhibitor
Bicarbonate
Cite
Citations (0)
Background: Acetazolamide has been used for diuretic-induced metabolic alkalosis, but the preferred dose, route, and frequency of administration remain unknown. Objective: The purpose of this study was to characterize dosing strategies and determine the effectiveness of intravenous (IV) and oral (PO) acetazolamide for patients with heart failure (HF) with diuretic-induced metabolic alkalosis. Methods: This was a multicenter, retrospective cohort study comparing the use of IV versus PO acetazolamide in patients with HF receiving at least 120 mg of furosemide for the treatment of metabolic alkalosis (serum bicarbonate CO 2 ≥32). The primary outcome was the change in CO 2 on the first basic metabolic panel (BMP) within 24 hours of the first dose of acetazolamide. Secondary outcomes included laboratory outcomes, such as change in bicarbonate, chloride, and incidence of hyponatremia and hypokalemia. This study was approved by the local institutional review board. Results: IV acetazolamide was given in 35 patients and PO acetazolamide was given in 35 patients. Patients in both groups were given a median of 500 mg of acetazolamide in the first 24 hours. For the primary outcome, there was a significant decrease in CO 2 on the first BMP within 24 hours after patients received the IV acetazolamide (−2 [interquartile range, IQR: −2, 0] vs 0 [IQR: −3, 1], P = 0.047). There were no differences in secondary outcomes. Conclusion and Relevance: IV acetazolamide resulted in significantly decreased bicarbonate within 24 hours of administration. IV acetazolamide may be preferred to treat diuretic-induced metabolic alkalosis in patients with HF.
Acetazolamide
Alkalosis
Cite
Citations (5)
Objective To analyze the acid-base imbalance of 21 SARS patients hospitalized in our hospital. Methods The Specimens of femoral arterial blood from patients with SARS were detected by gas-electrolyte analysis instrument. The simple acid-base imbalance was determined according to the values of PaCO3, HCO3- and pH; then whether it was mixed acid-base imbalance was assessed by counting these parameters according to the formula of acid-base imbalance; subsequently, based on the values of AC and Cl-↑of blood, whether it was trio acid-base imbalance was judged. Results (l)The acid-base imbalance of respiratory alkalosis was dominant type. (2)The mixed acid-base imbalance was more often found than simple one. (3)It was short of respiratory acidosis, respiratory acidosis and metabolic alkalosis, metabolic acidosis and metabolic alkalosis and trio acid-base imbalance. Conclusion The clinical characters of SARS are severity of patient' s condition, rapid deterioration of state of illness, with high fever, and the decrease of CO2 and HCO3- in blood caused by overventilation. The blood will tend to alkalosis, and the respiratory alkalosis happens easily with shorter compensation period,then the mixed acid-base imbalance may be resulted fast.
Respiratory alkalosis
Alkalosis
Respiratory acidosis
Acid–base imbalance
Respiratory compensation
Acid–base homeostasis
Base (topology)
Acid–base reaction
Arterial pH
Base excess
Cite
Citations (0)
Objective:To explore the types,characteristics and causes of alkalosis in critically ill patients.Methods:The clinical data,1 470 determinations of arterial blood gases and electrolytes in 868 critically ill patients were analyzed.Results:The types of alkalosis were ranked as following:respiratory alkalosis (868 determinations,45 44%),metabolic alkalosis (362 determinations,24 63%),respiratory alkalosis plus metabolic alkalosis (270 determinations,18 37%),triple acidbase disorders with respiratory alkalosis (102 determinations,6 94%),and respiratory acidosis plus respiratory alkalosis (68 determinations,4 63%).PaO 2 values below 8 kPa (1 kPa=7.5 mmHg) were obtained in 773 determinations (52.59%).The mechanism associated with the occurrence of alkalosis was multifactorial in these patients.Conclusions:Alkalosis occurred frequently in critically ill patients.The most common form was respiratory alkalosis with type Ⅰ respiratory failure.The primary disease might result in respiratory alkalosis and hypoxemia in patients with normal respiratory function,and incorrect treatment seems to be responsible for the occurrence of metabolic alkalosis.Triple acidbase disorders with respiratory alkalosis may frequently appear in critically ill patients with multiple organ dysfunction.
Respiratory alkalosis
Alkalosis
Respiratory acidosis
Pulmonary gas pressures
Cite
Citations (0)
Acetazolamide
Alkalosis
Bicarbonate
Base excess
Acid–base imbalance
Acid–base homeostasis
Cite
Citations (43)
Extracellular plasma pH (pHe) of nephrectomized male or female Sprague‐Dawley rats was changed by infusion of either sodium bicarbonate or HCl to predetermined values in the pH rangc of 7.53–7.14, and then held constant for 2 h. Intracellular pH (pHi) of the liver, heart, brain, and two skeletal muscle groups as calculated from the distribution of 14 C‐labelled DMO (5.5‐dimethyl‐2,4‐oxazolidinedione) was compared to corresponding tissues of a control group and rats treated with the carbonic anhydrase inhibitor acetazolamide (Diamox). When compared to control, changes of the extracellular pH in malr or fcmalr rats were followed by similar effects on pHi in the investigated tissues. At the same extracellular pH three were no statistical differences between pHi values of HC1 or acetazolamide treated rats, though thc arterial Pco 2 following acetazolamide administration was significantly increased when compared to control or thr corresponding HCl group. This study shows that administration of acetazolamide or HCl rcsrilts in a dosrdependent decrease of plasma and tissue pH, and that both agents may be used as a logical and safe therapy during severe metabolic alkalosis in rats.
Acetazolamide
Alkalosis
Carbonic anhydrase inhibitor
Intracellular pH
Bicarbonate
Acid–base homeostasis
Cite
Citations (12)
Acetazolamide is a carbonic anhydrase inhibitor normally used to reduce intraocular pressure in glaucoma. Metabolic alkalosis may be partially corrected by the use of acetazolamide. The most common cause of metabolic alkalosis on the ICU is usually the result of furosemide administration.
Acetazolamide
Carbonic anhydrase inhibitor
Cite
Citations (0)