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 45678. 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 49. In patients, NAC has been shown to increase the cardiac index and oxygen delivery in fulminant hepatic failure and in septic shock 4610. 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.

All patients were included after written informed consent of legislative and ethical committee approval. For continuous cardiovascular monitoring a fiber optic, pulmonary artery flotation catheter (Baxter Swan-Ganz^® Intelicath™ continuous cardiac output thermodilution catheter 139H – 7.5 French; Baxter/Edwards Critical-Care, Irvine, California, USA) and a radial artery catheter were inserted. After adequate fluid resuscitation, norepinephrine was titrated to maintain the mean arterial pressure between 70 and 90 mmHg. All patients were mechanically ventilated and received a continuous infusion of the analgesic sedatives fentanyl and flunitrazepam. The mechanical ventilation was pressure controlled (Servo 900 C; Siemens, Solna, Sweden), and ventilator settings were not altered during the study period. All patients were normoventilated (arterial carbon dioxide tension = 35–45 Torr). None of the patients had a change in body temperature > 0.5°C during the study period, as documented by continuous monitoring of a catheter thermistor.

Blood was collected and hemodynamic measurements were performed 1 hour before and 1 hour after NAC injection. Patients received 150 mg/kg body weight NAC as an intravenous bolus injection over 15 min. Each hemodynamic measurement included the heart rate and cardiovascular pressures with reference to the midaxillary line. The hemodynamic measurements were immediately followed by the withdrawal of mixed venous and radial artery blood samples. Part of each sample was immediately analyzed for arterial and mixed venous oxygen and carbon dioxide tensions (ABL 300; Radiometer, Copenhagen, Denmark), along with arterial and mixed venous hemoglobin content and oxygen saturation (Hemoximeter OSM-3; Radiometer).

An intravenous bolus of 1 mg/kg body weight lidocaine was injected 1 hour before and 1 hour after NAC administration. Blood samples to determine the MEGX test were taken before and 15 min after lidocaine injection. The serum concentration of the lidocaine metabolite MEGX was determined by means of a fluorescence polarization immunoassay (Abbott GmbH, Wiesbaden, Germany). MEGX concentration values measured before lidocaine administration were subtracted from concentrations measured after 15 min, and the results were reported as serum MEGX concentrations (ng/ml). Blood samples were centrifuged at 4650 × g for 10 min, and serum was stored at -80°C until analysis.

The measurements of bilirubin, aspartate aminotransferase, alanine aminotransferase and serum lactate were analyzed as part of the clinical routine (Clinical Chemistry Department).

Proton magnetic resonance spectroscopy (¹H-MRS) measurements for measurement of lactate liver intensities were acquired at a 1.5 Tesla clinical scanner (Magnetom Vision; Siemens) with a stimulated echo acquisition mode sequence. A fast imaging procedure was performed prior to spectroscopy using a technique involving a gradient echo sequence, fast low angle shot (FLASH 2D), while the breath was held for several seconds. In these images a volume of interest of 64 ml resolution was positioned in the liver parenchyma of the right lobe. A localized shimming procedure was performed. The number of acquisitions was 256. We used echo times of 135 ms and 270 ms, respectively, to differentiate between the fatty acid signal and the lactate signal at 1.35 ppm. This was necessary as both signals consist of almost identical resonance frequencies but have different phase angles at varied echo times. Evaluation of the spectra was performed by means of the LC Model program 15 and data are expressed in arbitrary units that correspond to micromoles per liter. The liver perfusion measurement was performed with the gadolinium-enhanced proton magnetic resonance (MR) imaging method 1617.

Five septic shock patients were evaluated. Septic shock was defined according to the criteria for septic shock of the American College of Chest Physicians Consensus Conference 18. All patients were studied within the first 24 hours of the onset of sepsis. Acute Physiology and Chronic Health Evaluation II 19 and Multiple Organ Dysfunction 20 scores were recorded. Basic patient characteristics, scores, outcome data, laboratory parameters and hemodynamic-related and ventilator-related data for each patient are presented in Table 1. The results for liver perfusion, liver lactate signal intensity and MEGX serum concentrations are shown in Figs 1,2,3, respectively.

The most important results of this report were threefold. There was a median decrease of 89% in lactate signal intensities in liver tissues, although the plasma lactate did not change markedly. Second, there was an increase in liver perfusion after NAC application and, finally, there was an improvement in liver function measured by the MEGX plasma concentration.

This report has shown, for the first time, that NAC decreases liver lactate signal intensities and increases perfusion measured by MR imaging and spectroscopy. The MEGX formation improved in all patients, probably due to a NAC-induced improvement in regional perfusion.

None declared.

• N-acetylcysteine decreases liver lactate signal intensities in magnetic resonance spectroscopy

• N-acetylcysteine increases liver perfusion measured by magnetic resonance imaging

• N-acetylcysteine improves MEGX formation

¹H-MRS = proton magnetic resonance spectroscopy; MEGX = monoethylglycinexylidide; MR = proton magnetic resonance; NAC = N-acetylcysteine; PaO₂/FiO₂ = partial arterial oxygen tension/inspirator oxygen fraction.