Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy

Atterbury, Colin E.; Maddrey, Willis C.; Conn, Harold O.

doi:10.1007/bf01072921

Cited by 249 publications

(167 citation statements)

References 12 publications

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“…We used the NCT-A, a stanExclusion criteria were the following: 1) active, major complicadardized psychometric test, for the diagnosis of SHE. 9,11,40 The availtions of portal hypertension, such as gastrointestinal hemorrhage, ability of four validated parallel forms of NCT-A and the inclusion hepatorenal syndrome, or spontaneous bacterial peritonitis; 2) acute of a trial run of a simpler form of NCT-A before the first use of the superimposed liver injury; 3) serious nonhepatic diseases such as test at the randomization point was the most reliable way of ensuring decompensated heart failure and/or respiratory failure, decompenthat learning effects were minimized. sated diabetes mellitus, renal insufficiency, or electrolyte imbalVenous Ammonia Concentration.…”

Section: Therapeutic Endpointsmentioning

confidence: 99%

“…Patients who met the following inclusion criteria Inclusion criteria were checked at a nonfixed time point at the assessed at the randomization (day 01) were eligible for the study: time of randomization (day 01) before any treatment or superim-1) chronic (persistent), manifest HE (mental state grade I or II, ac-posed protein load. Therefore, these parameters could not be used cording to the West-Haven criteria 9,11,40 developed spontaneously as baseline parameters for the analysis of primary and secondary without existence of specified precipitating factors or SHE (mental response variables. The baselines of postprandial NH 4 / , NCT-A, and state grade 0 and an NCT-A performance time ú 30 seconds); 9,11,40 HE-grading used in efficacy analyses were obtained after the first 2) hyperammonemia (venous ammonia concentration ú 50 mmol/ OA-or placebo-infusion (day 0; 1:00 PM).…”

Section: Therapeutic Endpointsmentioning

confidence: 99%

“…Therefore, these parameters could not be used cording to the West-Haven criteria 9,11,40 developed spontaneously as baseline parameters for the analysis of primary and secondary without existence of specified precipitating factors or SHE (mental response variables. The baselines of postprandial NH 4 / , NCT-A, and state grade 0 and an NCT-A performance time ú 30 seconds); 9,11,40 HE-grading used in efficacy analyses were obtained after the first 2) hyperammonemia (venous ammonia concentration ú 50 mmol/ OA-or placebo-infusion (day 0; 1:00 PM). From this point of view, L); 9,11 and 3) cooperative, hospitalized, adult patients with histologithe therapeutic effects after 2, 4, and 7 days of treatment will be cally proven cirrhosis or overt, clinically proven cirrhosis confirmed analyzed for these parameters at postprandial time points (1:00 PM).…”

Section: Therapeutic Endpointsmentioning

confidence: 99%

“…Because of this, no metric test for the assessment of mental function in cirrhotic patients with HE. 9,11,40 Psychometric tests were performed at significant improvements in comparison with placebo could be shown regarding mental state gradation and ammoniathe same time as the postprandial ammonia measurement and the evaluation of the patient's mental state. The aim was lowering in patients with initially existing SHE.…”

Section: Adverse Events and Adverse Drug Reactionsmentioning

confidence: 99%

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Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo-controlled, double-blind study

et al. 1997

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prandial venous ammonia concentrations in the OAOne hundred twenty-six patients with cirrhosis, hytreated group showed improvements in comparison perammonemia (ú50 mmol/L), and chronic (persistent) with placebo. In addition, venous fasting blood ammonia hepatic encephalopathy (HE), which developed spontaconcentration (P õ .01), mental state gradation (P õ neously without the existence of known precipitating .001), and PSEI (P õ .01), which includes the mental state factors, were enrolled in a randomized, double-blind, gradation, NCT-A time, and postprandial venous ammoplacebo-controlled clinical trial of intravenously adminnia in this trial, improved to a much higher degree in Hepatic encephalopathy (HE) is one of the major complicapresented are based on the total study sample (intent-to-tions of cirrhosis. Five years after the diagnosis of cirrhosis, treat analysis), which included 63 patients in the placebo the probability of developing at least one episode of this spegroup and 63 patients in the OA group. Of the 126 pa-cific form of decompensated cirrhosis is in the range of 26%. 1 tients, 114 met all the criteria for inclusion and com-Once clinical decompensation has occurred, however, the pleted the trial and treatment as outlined in the protocol prognosis (16% 1 to 22% 2 probability of survival at 5 years) (treated-per-protocol analysis). During baseline, the pla-compared with a survival probability of 55% 2 to 70% 1 in circebo and treatment groups were homogeneous with re-rhotic patients without HE is very poor. 1,2 Therefore, prevengard to mental states, NCT-A performance time, fasting tion and effective treatment of HE may have important progvenous blood ammonia levels, and Child-Pugh criteria. nostic implications in cirrhotic patients. Although a slight improvement occurred in the placeboHyperammonemia 3,4 by a variety of postulated mechagroup, NCT-A performance times (P õ .001) and post-nisms 3-8 is felt to be one of the primary pathogenetic factors in the development of HE. 8 The majority of therapeutic measures currently in use are therefore directed at reducing blood Abbreviations: HE, hepatic encephalopathy; SHE, subclinical hepatic encephalopathy; ammonia levels, 9-13 mainly by diminishing enteric ammonia OA, L-ornithine-L-aspartate; GS, glutamine synthetase; NCT-A, number connection test A; PSEI, portal systemic encephalopathy index.production. Otherwise, it is known that liver and muscle play From the 1 Martin-Luther-University Halle-Wittenberg, Department of Internal Median important part within the ammonia detoxification system, cine, Halle;

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Section: Therapeutic Endpointsmentioning

confidence: 99%

Section: Therapeutic Endpointsmentioning

confidence: 99%

Section: Therapeutic Endpointsmentioning

confidence: 99%

Section: Adverse Events and Adverse Drug Reactionsmentioning

confidence: 99%

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Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo-controlled, double-blind study

et al. 1997

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“…23 Other antimicrobials, including metronidazole and vancomycin, have been studied to a more limited extent than neomycin. 24,25 …”

Section: Antimicrobial Agents For Hepatic Encephalopathymentioning

confidence: 99%

Management of Overt Hepatic Encephalopathy

Sharma

2015

Journal of Clinical and Experimental Hepatology

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Hepatic encephalopathy (HE) is an important complication of cirrhosis with significant morbidity and mortality. Management of HE primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as non-absorbable disaccharides, antimicrobial agents like rifaximin and L-ornithine L-aspartate. The non-absorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and in primary and secondary prophylaxis of HE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Rifaximin is effective in treatment of HE and recent systemic reviews found it comparable to disaccharides and is effective in secondary prophylaxis of HE. H epatic encephalopathy (HE) is a complex neuropsychiatric syndrome, which may complicate acute, chronic liver failure or patients with portal-systemic shunting. It is characterized by changes in mental state including a wide range of neuropsychiatric symptoms ranging from minor signs of altered brain function to deep coma. 1,2 It is one of the commonest indications for admission in intensive care unit in patients with advanced cirrhosis. There were over 40 000 patients hospitalized in the United States alone for a primary diagnosis of HE, resulting in total charges of approximately $932 million. Data in other countries are lacking, hence it causes a huge burden financially to the patient and society. 3 The West Haven Criteria are most often used to grade HE, with scores ranging from I-IV (IV being coma). However, it is a challenge to diagnose patients with minimal hepatic encephalopathy (MHE) or grade 1 HE; so it might be practical to combine these entities and name them covert HE for clinical use and overt HE to patients with grade II to IV. 1,4,5 One of the major tenets of the pathophysiology of HE is hyperammonemia that results from an increased nitrogenous load from the gastrointestinal tract and reduced urea synthesis both due to portal-systemic shunting and decreased urea hepatic synthesis. Brain and skeletal muscle neither remove nor produce ammonium in normal conditions, but they are able to seize ammonium during hyperammonemia, releasing glutamine. Ammonia is produced both by bacterial degradation of amines, aminoacids, purines, and urea as well as enterocytic glutaminase activity that converts glutamine to glutamate and ammonia. 6,7 Astrocytes play an important role in the pathogenesis of HE with consequences for neuronal function. Astrocytes have the ability to eliminate ammonia by the synthesis of glutamine through amidation of glutamate by the enzyme glutamine synthetase Hyperammonemia leads to the accumulation of glutamine within astrocytes, which exerts an osmotic stress that causes astrocytes to take in water and swell. 8,9 This article reviewed the clinical impact, pathogenesis, and management of overt HE in patients with cirrhosis. Articles published between January 1960 and November 2013 were acquired through a MEDLINE search of different combi...

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Blindness Induced by Double-blindedness

Conn¹

1981

Arch Intern Med

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Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy

Cited by 249 publications

References 12 publications

Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo-controlled, double-blind study

Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo-controlled, double-blind study

Management of Overt Hepatic Encephalopathy

Blindness Induced by Double-blindedness

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