We have previously demonstrated that non-selective nitric oxide synthase (NOS) inhibition did not reverse the LPS-induced deterioration of hepato-splanchnic energy status in porcine endotoxic shock. Therefore, this study investigated the effect of selective inducible NOS (iNOS) inhibition using 1400 W on intestinal and liver perfusion, O2 kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia, continuous intravenous infusion of 1400 W was started until the end of the experiment and was titrated to maintain mean blood pressure (MAP) at baseline levels. Twelve, 18, and 24 h after starting LPS, we measured hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal as well as hepatic venous lactate/pyruvate ratios, and endogenous glucose production rate. Expired NO and plasma nitrate levels were assessed as a measure of NO production. 1400 W decreased LPS-induced increase in expired NO and allowed for the maintenance of MAP without modification of cardiac output. Despite unchanged regional macrocirculation, 1400 W prevented the progressive rise of ileal mucosal-arterial PCO2 gap, significantly improved the LPS-induced impairment of hepato-splanchnic redox state, and blunted the decline in liver lactate clearance. Increased glucose production rate was not influenced. Thus, the selective iNOS inhibition with 1400 W prevented circulatory failure and largely attenuated otherwise progressive LPS-induced deterioration of intestinal and hepatocellular energy metabolism.
To study the influence of positive endexpiratory pressure (PEEP) ventilation on metabolic parameters with specific regard to liver metabolism.Prospective experimental study on the effects of PEEP ventilation on hemodynamic and gas exchange as well as metabolic parameters, i.e. hepatic glucose production, arterial, hepatic and portal venous insulin, glucagon, free fatty acid (FFA), glycerol, beta-hydroxybutyrate and lactate concentrations.Experimental Laboratory Unit of the University Hospital.10 Labrador Beagle dogs (18-22 kg) were studied.Animals were ventilated with PEEP of 0, 7.5, 15, and 0 mm Hg, each level lasting 2 h.PEEP 15 significantly increased heart rate from 110(70) to 220(55) beats/min and decreased cardiac output from 2.5 (2.0) to 1.5 (0.8) l/min. This was associated with significant increases in mean pulmonary artery pressure, pulmonary artery occlusion pressure, portal and hepatic venous pressure, whereas mean systemic pressure did not change. While whole-body oxygen consumption and respiratory quotient remained constant, whole-body oxygen delivery significantly decreased from 456(266) to 294(168) ml/min during PEEP 15 concomitant to augmented whole-body oxygen extraction (from 27(34) to 51(33)%). Oxygen extraction from the splanchnic organs increased from 41(31) to 81(30)%. Hepatic venous oxygen tension (PhvO2) and hemoglobin oxygen saturation (ShvO2) during PEEP 15 decreased from 41(18) to 28(47) mm Hg and from 60(31) to 18(66)%, respectively. Hepatic glucose production was significantly stimulated from 3.44(1.44) to 3.92(1.83) mg/kg/min at PEEP 15. Arterial and portalvenous glucagon/insulin ratios did not change. FFA and glycerol concentrations depending on PEEP levels were significantly higher in the hepatic artery and portal vein than in the hepatic vein. Compared to portal venous and arterial hepatic concentrations, hepatic venous beta-hydroxybutyrate significantly increased with rising PEEP levels.Low values of PhvO2 and ShvO2 during PEEP 15 gave evidence for hypoxia of the liver. This was associated with a stimulated hepatic glucose production rate accompanied by enhanced hepatic uptake and utilization of FFA serving as fuel substrates. As the rate of gluconeogenesis is a major determinant of hepatic oxygen consumption these metabolic effects of PEEP ventilation have to be considered during states of critical illness.
Our aim is to report the results of the 'liver indication' subset of patients in the CytoSorb International Registry.Structured data were recorded. Treatment characteristics and changes from T1 (start of hemoadsorption) to T2 (termination) were evaluated with a special focus on bilirubin, C-reactive protein, procalcitonin, interleukin-6, platelet levels, SOFA scores, mortality, and subjective assessment by the attending physicians.Until January 2021, from the total 1434 patients, 109 (age: 49.2 ± 17.1 years, 57.8% males) received treatment for hyperbilirubinemia. APACHE II-predicted mortality was 49.6 ± 26.8%. In the study, 91% of patients were alive at the termination of hemoadsorption and improvement was observed by the physicians in 75 cases. Overall, 65 (59.6%) patients died in the hospital, and 60 (55.0%) died in the ICU. Patients received a median of two treatments for a median of 43 h (interquartile range: 24-72 h) in total. Serum bilirubin levels reduced significantly to -4.6 (95% CI: -6.329 to -2.8) mg/dL. Thrombocytopenia was reported in four patients as an adverse event.We report the largest case series on hemoadsorption for 'liver indication' from the CytoSorb International Registry. The finding of significant bilirubin removal observed in our study could have substantial impact in designing and executing further studies on the effects of hemoadsorption in liver dysfunction, which are certainly warranted.
The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and “other” reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).
