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The Effect of Selective Intestinal Decontamination on the Hyperdynamic Circulatory State in Cirrhosis: A Randomized Trial

Brindhesha Rasaratnam, , MBBS, FRACP; David Kaye, , MBBS, FRACP, PhD; Garry Jennings, , MBBS, FRACP, MD; Francis Dudley, , MBBS, FRACP, MD; and Jaye Chin-Dusting, PhD
[+] Article and Author Information

From Alfred Hospital and Baker Medical Research Institute, Prahran, Victoria, Australia.


Ann Intern Med. 2003;139(3):186-193. doi:10.7326/0003-4819-139-3-200308050-00008
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Chronic peripheral vasodilatation is the hallmark hemodynamic abnormality in cirrhosis and has important prognostic implications. Decreased mean arterial pressure and systemic vascular resistance are independently associated with a poorer prognosis in cirrhotic patients (1), and splanchnic and peripheral vasodilatation contribute to the pathogenesis of portal hypertension and ascites production (1213). Although no clinical studies have been done, correcting the factors that are central to the development of systemic vasodilatation may improve the clinical course of patients with cirrhosis.

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Figure 1.
Flow chart of the study design.

In effect, there were two separate studies: a cross-sectional study of the physiologic differences between cirrhotic patients and healthy controls and a randomized crossover study of treatment in cirrhotic patients. A study day consisted of 1) forearm venous occlusion plethysmography; 2) cardiac output measurements; 3) mean arterial pressure assessment; 4) hepatic venous pressure gradient measurement; 5) glomerular filtration rate; and 6) blood sampling for complete blood count, renal function, liver function tests, renin and aldosterone levels, and endotoxin level.

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Figure 2.
End points before and after treatment with norfloxacin for plasma endotoxin levels (A), mean artrial pressure (B), forearm blood flow (C), forearm vascular resistance (D), and cardiac output (E).black circlesmiddle horizontal lineupper and lower horizontal lines

The dotplot of points represent individual changes ( ) as well as mean change ( ; values are stated below the dotplots) and 95% CIs ( ) for each respective end point. All measurements represent 14 patients, with the exception of endotoxin, which represents 13 patients.

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Figure 3.
End points before and after treatment with norfloxacin for systemic vascular resistance (A), hepatic venous pressure gradient (B), renin level (C), aldosterone level (D), and inulin clearance (E).black circlesmiddle horizontal lineupper and lower horizontal lines−1−1

The dotplot of points represent individual changes ( ) as well as mean change ( ; values are stated below the dotplots) and 95% CIs ( ) for each respective end point. All measurements represent 14 patients, with the exception of renin, which represents 13 patients. To convert renin levels to ng · L · s , multiply by 0.2778. To convert aldosterone levels to ng/dL, divide by 27.74. To convert inulin clearance to mL/s, multiply by 0.0167.

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Summary for Patients

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

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.

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