Acetazolamide improves central sleep apnea in heart failure

Since sleep apnea is associated with heart failure, patients who take a single dose of acetazolamide - a mild diuretic and respiratory stimulant - before going to bed exhibit less sleep apnea, improved blood oxygen levels and fewer daytime symptoms of sleepiness.

The results of the double-blind, placebo-controlled study appear in the second issue for January 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Shahrokh Javaheri, M.D., of the Pulmonary Service in the Department of Veterans Affairs Medical Center and Department of Medicine at the University of Cincinnati College of Medicine in Cincinnati, Ohio, studied 12 male patients with stable heart failure who had more than 15 episodes per hour each night of sleep apnea (breathing pauses during sleep lasting 10 seconds or more.)

In heart failure, the quantity of blood pumped each minute by the heart is insufficient to meet the body's requirements for oxygen and nutrients.

In the past, acetazolamide's principal use has been to help treat breathing irregularities and sleep apneas occurring at high altitude.

According to the authors, the 12 patients with stable heart failure were randomized to a double-blind cross-over protocol with either acetazolamide or placebo, taken one hour before bedtime over the course of six nights. There was a two-week washout period between the two study segments--acetazolamide and placebo.

"An important finding of the double-blind study was the significant improvement in patient perception of improved sleep quality, waking up more refreshed, with less daytime fatigue and sleepiness while taking acetazolamide, compared with placebo," said Dr. Javaheri.

The average age of the patients was 66. There were no significant patient differences in body mass index levels, blood pressure or heart rate during the two phases of the study.

Each patient underwent a sleep test, an analysis of blood gases as well as a pH study (a test of acidity or alkalinity), a measurement of serum electrolytes, a pulmonary function test, plus other measurements at the start of the study and at the completion of each arm (acetazolamide and placebo).

"We hypothesize that with long-term drug therapy, as sleep-related breathing disorders improve, it may be reflected in an improvement in cardiac function that will further improve periodic breathing, resulting in a positive feedback cycle," said Dr. Javaheri. "Improvement in sleep apnea may assist cardiac function by a variety of mechanisms such as improved oxygenation."

The author points out that since the short-term efficacy of the drug has been documented, more long-term studies are needed to measure patient cardiac function, quality of life and the levels of norepinephrine in the plasma and urine. (Norepinephrine is a hormone used to maintain blood pressure and to treat cardiac arrest.)