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John Benz
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NAC and the liver
N-acetylcysteine Decreases Lactate Signal Intensities in Liver Tissue and Improves Liver Function in Septic Shock Patients, as Shown by Magnetic Resonance Spectroscopy: Extended Case Report
Posted 03/31/2004
Ortrud Vargas Hein; Renate ?hring; Andreas Schilling; Michael Oellerich; Victor W Armstrong; Wolfgang J Kox; Claudia Spies
Abstract and Introduction
Abstract
Background: N-acetylcysteine (NAC) has been shown to improve splanchnic blood flow in experimental studies. This report evaluates the effects of NAC on liver perfusion and lactate signal intensities in the liver tissue of septic shock patients using proton magnetic resonance imaging and spectroscopy. Furthermore, the monoethylglycinexylidide (MEGX) test was used to investigate hepatic function.
Methods: Five septic shock patients received 150 mg/kg body weight NAC as an intravenous bolus injection over 15 min. Lidocaine was injected both prior to and following NAC administration in order to determine MEGX formation. Measurements (hemodynamics, oxygen transport-related variables, blood samples for lactate, liver-related markers) were performed 1 hour before and 1 hour after NAC injection. In addition to the proton magnetic resonance imaging patients received two proton magnetic resonance spectra, one prior to and one 30 min subsequent to the onset of the NAC infusion at a 1.5 Tesla clinical scanner, for measurement of liver perfusion and liver lactate signal intensity.
Main Findings: Following NAC infusion, the lactate signal intensity in the liver tissue showed a median decrease of 89% (11?99%), there was a median increase in liver perfusion of 41% (-14 to 559%), and the MEGX serum concentration increased three times (1.52?5.91).
Conclusions: A decrease in the lactate signal intensity in the liver tissue and an increase in the MEGX serum concentration and in liver perfusion might indicate improved liver function as a result of NAC administration. Patients with compromised hepatosplanchnic function, such as patients with septic shock due to peritonitis, may therefore benefit from NAC therapy.
Introduction
In septic shock, the vasoconstriction in splanchnic vessels is disproportionally greater than in other vascular beds and may persist despite the presence of normal systemic hemodynamic measurements.[1] Takala and Ruokonen found, in spite of normal global cardiopulmonary physiology, that inadequate perfusion and oxygenation of the splanchnic region increases the risk of Multiple Organ Dysfunction Syndrome.[2] The gut is described as the 'motor' of Multiple Organ Dysfunction Syndrome.[3]
N-acetylcysteine (NAC), a precursor of glutathione synthesis, can exert important antioxidant cytoprotective effects and anti-inflammatory effects.[4-8] When endotoxic shock occurred, there was a significant increase in the absolute mesenteric blood flow but not in the fractional blood flow (i.e. hepatic flow index/cardiac index) following NAC administration.[4,9] In patients, NAC has been shown to increase the cardiac index and oxygen delivery in fulminant hepatic failure and in septic shock.[4,6,10] Devlin and colleagues showed in a recent study that the indocyanine green elimination in patients with hepatic dysfunction increased after NAC administration.[11] It is not clear, however, whether the increase in elimination rate is related to an increased hepatosplanchnic perfusion or to a better hepatic function.[12]
The aim of this report was therefore to investigate whether the administration of NAC improves liver function and liver blood flow in septic shock patients. Owing to the fact that splanchnic dysoxia is usually presumed in sepsis,[13] we focused on the measurement of lactate in the liver tissue accumulating following cell dysfunction.[14] Furthermore, the monoethylglycinexylidide (MEGX) test was used to investigate hepatic function.
Ortrud Vargas Hein1, Renate ?hring2, Andreas Schilling2, Michael Oellerich3, Victor W Armstrong3, Wolfgang J Kox1, Claudia Spies1
1Department of Anesthesiology and Intensive Care Medicine Charit?, Campus Mitte, Humboldt University Berlin, Germany
2Department of Neurology, Benjamin Franklin Medical Center, Free University Berlin, Germany
3Department of Clinical Chemistry, Georg-August University G?ttingen, Germany
