Oral Administration of an Antibiotic (Norfloxacin) May Help Treat the Cardiac and Circulatory Complications of Liver Failure

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The summary below is from the full report titled "The Effect of Selective Intestinal Decontamination on the Hyperdynamic Circulatory State in Cirrhosis. A Randomized Trial." It is in the 5 August 2003 issue of Annals of Internal Medicine (volume 139, pages 186-193). The authors are B. Rasaratnam, D. Kaye, G. Jennings, F. Dudley, and J. Chin-Dusting.

What is the problem and what is known about it so far?

Advanced liver failure affects many organs in addition to the liver. For example, when the liver fails, the circulatory system reacts by relaxing the muscular coating that surrounds blood vessels. This allows blood vessels to open wider, causing blood to flow more rapidly through the vessels. As a result, to maintain blood pressure at safe levels, the heart must beat faster and the amount of blood pumped by the heart (the cardiac output) must increase. This altered condition of the circulatory system, known as a "hyperdynamic circulatory state," puts a dangerous strain on the heart and may cause death. Certain types of bacteria cause this problem when they invade the bloodstream. Doctors have speculated that the circulatory changes that accompany liver failure occur because the liver, which normally removes bacteria that leak into the bloodstream from the bowel, can no longer perform this function. Until now, no effective treatment has been available for the hyperdynamic circulatory state that accompanies liver failure.

Why did the researchers do this particular study?

To find out whether oral administration of norfloxacin (an antibiotic that kills bacteria in the bowel) could block the effects of liver failure on the circulatory system.

Who was studied?

14 men with alcohol-related liver disease (cirrhosis) who were compared to 14 healthy male volunteers of the same age.

How was the study done?

Participants with cirrhosis were randomly assigned to receive either norfloxacin capsules or placebo capsules (that looked exactly like norfloxacin) for 28 days. Neither the patient nor the doctor knew which capsule was being taken. After 28 days of treatment, the capsules were switched; the participants who had taken norfloxacin were given placebo and those who had taken placebo were given norfloxacin for another 28 days. At the end of each treatment period, a blood sample was drawn in participants with cirrhosis to test for the presence of bacterial products in the bloodstream (endotoxins) and for the level of natural chemicals that maintain blood pressure. In addition, the researchers measured cardiac output and kidney function. Normal volunteers underwent studies only once and received no medication.

What did the researchers find?

Measurements in normal participants were compared with the results in cirrhotic participants who took norfloxacin or placebo. When cirrhotic persons took norfloxacin capsules, blood pressure improved, blood flow through the vessels became more normal, and cardiac output decreased slightly (but not significantly). Norfloxacin had no effect on how well the kidneys were working.

What were the limitations of the study?

The researchers could not confirm the exact way that norfloxacin caused the circulatory changes that they observed. Additional factors must be involved in producing the hyperdynamic circulatory state because norfloxacin did not completely block its manifestations.

What are the implications of the study?

Oral administration of norfloxacin may be helpful in treating a dangerous side effect of liver failure.