Biomaterial Database

Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease. 2001

P W Jones, and M Greenstone

Division of Physiological Medicine, St George's Hospital Medical School, Cranmer Terrace, Tooting, London, UK, SW17 ORE. pjones@sghms.ac.uk

BACKGROUND Carbonic anhydrase inhibitors such as acetazolamide cause a mild metabolic acidosis and may stimulate breathing. Some patients with severe chronic obstructive pulmonary disease (COPD) develop chronic hypercapnic ventilatory failure. In theory, they may benefit from use of these drugs with a fall in arterial carbon dioxide level (PCO2) and a rise in arterial oxygen (PO2). OBJECTIVE To determine the effectiveness and safety of acetazolamide in the treatment of hypercapnic ventilatory failure due to COPD SEARCH STRATEGY: The Cochrane Register of Controlled Clinical Trials was searched along with Medline, Embase, Central and CINAHL for relevant randomised control trials. METHODS Trials were included in the review provided they were placebo controlled, carried out in patients with stable chronic ventilatory failure due to COPD. METHODS Data were extracted and analysed by two reviewers (PJ and MG) and agreement was reached by consensus. Where data could be aggregated they were analysed using a fixed efefcts model and reported as a weighted mean difference (WMD) and its associated 95% confidence interval (95% CI). RESULTS Four trials were included in the review. Of these, two were randomised parallel studies, one was a crossover study and the other had a sequential design. A total of 84 patients were involved. Study quality was mixed and the studies were short (typically two weeks). All studies showed a similar direction and size of effect. In the randomised parallel studies, acetazolamide caused a metabolic acidosis and produced a non-significant fall in PCO2 (WMD -0.41 kPa; 95% CI -0.91, 0.09; N=2) and a significant rise in PO2 (WMD 1.54 kPa; 95% CI 0.97, 2.11; N=2). One study reported an improvement in sleep but there were no data concerning outcomes such as health status, symptoms, exacerbation rate, hospital admissions or deaths. Side effects were reported infrequently. CONCLUSIONS Acetazolamide can produce a small increase in arterial PO2 and fall in PCO2. These conclusions are drawn from a few small short studies that were not all of high quality. It is not known whether this physiological improvement is associated with clinical benefit.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D012131	Respiratory Insufficiency	Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)	Acute Hypercapnic Respiratory Failure,Acute Hypoxemic Respiratory Failure,Hypercapnic Acute Respiratory Failure,Hypercapnic Respiratory Failure,Hypoxemic Acute Respiratory Failure,Hypoxemic Respiratory Failure,Respiratory Depression,Respiratory Failure,Ventilatory Depression,Depressions, Ventilatory,Failure, Hypercapnic Respiratory,Failure, Hypoxemic Respiratory,Failure, Respiratory,Hypercapnic Respiratory Failures,Hypoxemic Respiratory Failures,Respiratory Failure, Hypercapnic,Respiratory Failure, Hypoxemic,Respiratory Failures
D002257	Carbonic Anhydrase Inhibitors	A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.	Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D002986	Clinical Trials as Topic	Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.	Clinical Trial as Topic
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006935	Hypercapnia	A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood.
D000086	Acetazolamide	One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)	Acetadiazol,Acetazolam,Acetazolamide Sodium, (Sterile),Acetazolamide, Monosodium Salt,Ak-Zol,Apo-Acetazolamide,Diacarb,Diamox,Diuramide,Défiltran,Edemox,Glauconox,Glaupax,Huma-Zolamide,Ak Zol,AkZol,Apo Acetazolamide,ApoAcetazolamide,Huma Zolamide,HumaZolamide
D029424	Pulmonary Disease, Chronic Obstructive	A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.	Airflow Obstruction, Chronic,COAD,COPD,Chronic Airflow Obstruction,Chronic Obstructive Airway Disease,Chronic Obstructive Lung Disease,Chronic Obstructive Pulmonary Disease,Chronic Obstructive Pulmonary Diseases,Airflow Obstructions, Chronic,Chronic Airflow Obstructions