Karl Träger

Glucose and urea production and leucine, ketoisocaproate and alanine fluxes at supraphysiological plasma adrenaline concentrations in volunteers

ObjectiveTo determine the magnitude and time course of adrenergic effects on metabolism in volunteers and possible implications for the use of sympathomimetics in the critically ill.DesignDescriptive laboratory investigation.Subjects7 volunteers.InterventionPrimed continuous infusions of stable isotope tracers ([15N2]-urea, [6,6-D2]-glucose, [methyl-D3]-L-leucine, [15N]-L-alanine) were used. After isotopic steady state had been reached an infusion of adrenaline (0.1 μg/kg/min) was administered (4 h). Isotopic enrichment was measured using gas chromatography-mass spectrometry and the corresponding rates of appearance were calculated.Measurements and main resultsGlucose production increased from 14.1±1.2 to 21.5±2.0 μmol/kg/min (p<0.05) after 80 min of adrenergic stimulation and then decreased again to 17.9±1.2 μmol/kg/min after 240 min. Leucine and ketoisocaproate (KIC) fluxes were 2.3±0.2 and 2.6±0.2 μmol/kg/min, respectively, at baseline and gradually decreased to 1.8±0.2 and 2.2±0.1 μmol/kg/min, respectively, after 240 min of adrenaline infusion (bothp<0.05). Alanine flux increased from 3.7±0.5 to 6.9±0.9 μmol/kg/min (p<0.05) after 80 min of adrenergic stimulation. Urea production slightly decreased from 4.8±0.9 to 4.3±0.8 μmol/kg/min during adrenaline (p<0.05).ConclusionsAdrenaline induced an increase in glucose production lasting for longer than 240 min. The decrease in leucine and KIC flux suggests a reduction in proteolysis, which was supported by the decrease in urea production. The increase in alanine flux is therefore most likely due to an increase in de-novo synthesis. The ammonia donor for alanine synthesis in peripheral tissues and the target for ammonia after alanine deamination in the liver remain to be investigated. These results indicate that adrenaline infusion most probably will not promote already enhanced proteolysis in critically ill patients. Gluconeogenesis is an energy consuming process and an increase may deteriorate hepatic oxygen balance in patients.

PEEP and hepatic metabolic performance in septic shock

Sir: Septic shock is accompanied by enhanced splanchnic 02 consumption, which may result in regional hypoxia due to a mismatch between splanchnic O 2 supply and demand. Ventilation with positive end-expiratory pressure (PEEP) may reduce cardiac output and thereby impair hepatic [1, 2] and, possibly, overall splanchnic blood flow, but little is known about the effects of PEEP on hepatic metabolism in septic shock. A surrogate for hepatic perfusion and oxygenation can be obtained by measuring hepatic venous 02 saturation (ShvO2) [3]. Since positive pressure ventilation has been demonstrated to impair lidocaine kinetics [4], we investigated whether the PEEP-induced fall in global blood flow is accompanied by impaired ShvO 2 as well as simultaneous alterations in metabolic performance. Hepatic metabolic performance was estimated by assessing hepatic glucose production (HGP), an organ-sepcific highly O2-demanding metabolic pathway. We included 15 consecutive patients with septic shock who had all been treated prior to the study to achieve the targets defined by Shoemaker et al. (DOz>600 ml/min per m 2, C1 >_ 4 l/rain per m z, VO2> 160 ml/min per m 2) by volume expansion, packed red cells, and dobutamine (5 -12 ~tm/kg per min); oxygen delivery and consumption prior to 8 0 -

Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs: effects on intestinal oxygen exchange and energy balance.

OBJECTIVES To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. DESIGN Prospective, randomized, experimental study with repeated measures. SETTING Investigational animal laboratory. SUBJECTS Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. INTERVENTIONS Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. MEASUREMENTS AND MAIN RESULTS ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal PCO2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. CONCLUSIONS Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.

Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series.

The use of cardiopulmonary bypass (CPB) in cardiothoracic surgery results in a well-known activation of the immunologic response. In some cases, however, this triggered immunologic response may be excessive, leading to a severe systemic inflammatory response syndrome (SIRS) and induced organ dysfunction. For example, patients frequently develop hemodynamic instability with hypotension and low systemic vascular resistance. To date, different therapeutic approaches, such as steroids, have been tried to control this maladaptive postoperative SIRS response, yet definitive proof of clinical efficacy is missing. A new cytokine adsorber device (CytoSorb; CytoSorbents) may be a useful approach to control hyperinflammatory systemic reactions by reducing a broad range of proinflammatory cytokines and other inflammatory mediators. This may, in turn, help to reestablish a physiologic immune response and help to restore deranged clinical parameters in these patients. In this retrospective case series study, we describe 16 cardiac surgery patients following prolonged CPB with post-CPB SIRS and subsequent acute kidney injury, who were then treated with hemoadsorption using CytoSorb in combination with continuous renal replacement therapy (CRRT). Treatment of patients with CytoSorb who presented with severe post-CPB SIRS resulted in a reduction of elevated cytokine levels, which was associated with a clear stabilization of deranged hemodynamic, metabolic, and organ function parameters. Treatment was well tolerated and safe, with no device-related adverse events occurring. CytoSorb therapy combined with CRRT is a potentially promising new treatment approach to achieve hemodynamic stability, cytokine reduction, and improved organ function in cardiac surgery patients who develop post-CPB SIRS.

Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs

We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.

Cytokine Reduction in the Setting of an ARDS-Associated Inflammatory Response with Multiple Organ Failure

A 45-year-old male was admitted to our hospital with a small bowel obstruction due to torsion and was immediately scheduled for surgical intervention. At anesthesia induction, the patient aspirated and subsequently developed a severe SIRS with ARDS and multiple organ failure requiring the use of ECMO, CRRT, antibiotics, and low dose steroids. Due to a rapid deterioration in clinical status and a concurrent surge in inflammatory biomarkers, an extracorporeal cytokine adsorber (CytoSorb) was added to the CRRT blood circuit. The combined treatment resulted in a rapid and significant reduction in the levels of circulating inflammatory mediators. This decrease was paralleled by marked clinical stabilization of the patient including a significant improvement in hemodynamic stability and a reduced need for norepinephrine and improved respiratory function as measured by PaO2/FIO2, ventilator parameters, lung mechanics, and indirect measures of capillary leak syndrome. The patient could be discharged to a respiratory weaning unit where successful respiratory weaning could be achieved later on. We attribute the clinical improvement to the rapid control of the hyperinflammatory response and the reduction of inflammatory mediators using a combination of CytoSorb and these other therapies. CytoSorb treatment was safe and well tolerated, with no device-related adverse effects observed.

Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series

Introduction Infective endocarditis is a serious disease condition. Depending on the causative microorganism and clinical symptoms, cardiac surgery and valve replacement may be needed, posing additional risks to patients who may simultaneously suffer from septic shock. The combination of surgery bacterial spreadout and artificial cardiopulmonary bypass (CPB) surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyperinflammatory state frequently associated with compromised hemodynamic and organ function. Hemoadsorption might represent a potential approach to control the hyperinflammatory systemic reaction associated with the procedure itself and subsequent clinical conditions by reducing a broad range of immuno-regulatory mediators. Methods We describe 39 cardiac surgery patients with proven acute infective endocarditis obtaining valve replacement during CPB surgery in combination with intraoperative CytoSorb hemoadsorption. In comparison, we evaluated a historical group of 28 patients with infective endocarditis undergoing CPB surgery without intraoperative hemoadsorption. Results CytoSorb treatment was associated with a mitigated postoperative response of key cytokines and clinical metabolic parameters. Moreover, patients showed hemodynamic stability during and after the operation while the need for vasopressors was less pronounced within hours after completion of the procedure, which possibly could be attributed to the additional CytoSorb treatment. Intraoperative hemoperfusion treatment was well tolerated and safe without the occurrence of any CytoSorb device-related adverse event. Conclusions Thus, this interventional approach may open up potentially promising therapeutic options for critically-ill patients with acute infective endocarditis during and after cardiac surgery, with cytokine reduction, improved hemodynamic stability and organ function as seen in our patients.

Elimination Rates of Electrolytes, Vitamins, and Trace Elements during Continuous Renal Replacement Therapy with Citrate Continuous Veno-Venous Hemodialysis: Influence of Filter Lifetime

Background/Aims: During continuous renal replacement therapy, relevant losses of nutritional substrates, vitamins, and trace elements via the filter may occur. We investigated filter lifetime efficiency during a 72-h treatment period. Methods: This prospective study included 40 patients undergoing citrate continuous veno-venous hemodialysis (CVVHD). The elimination rates were measured at 24, 48, and 72 h. To assess the influence of filter lifetime, we determined substrate loss every 24 h over a 72-h interval. Results: Filter lifetime did not affect the loss of ionized calcium, inorganic phosphate, magnesium, zinc, folic acid, and vitamin B12. Nevertheless, we did observe clinically significant loss of ionized calcium and inorganic phosphate during CVVHD that required supplementation. Conclusions: CVVHD leads to significant loss of ionized calcium and inorganic phosphate that is independent of the filter lifetime.

Kasuistik mit Literaturübersicht – Protamingabe bei Patientin mit Fischeiweißallergie

Protamine is a protein mainly used to reverse anticoagulant effects of heparin during cardiac or vascular surgery with extracorporeal circulation. Adverse events after protamine administration are rare but if they occur they can be catastrophic. Based on a case report with an elective cardiac surgery patient with known allergy to fish, we discuss the related events and risk factors for an adverse reaction after protamine. The patient management and its outcome are presented.

Extracorporeal membrane oxygenation and cytokine adsorption

Extracorporeal membrane oxygenation (ECMO) is an increasingly used technology for mechanical support of respiratory and cardio-circulatory failure. Excessive systemic inflammatory response is observed during sepsis and after cardiopulmonary bypass (CPB) with similar clinical features. The overwhelming inflammatory response is characterized by highly elevated pro- and anti-inflammatory cytokine levels. The excessive cytokine release during the overwhelming inflammatory response may result in multiple organ damage and failure. During ECMO therapy activation of complement and contact systems occur which may be followed by cytokine release. Controlling excessively increased cytokines may be considered as a valuable treatment option. Hemoadsorption therapy may be used to decrease cytokine levels in case of excessive inflammatory response and due to its unspecific adsorptive characteristics also substances like myoglobin, free hemoglobin or bilirubin. Controlling pro-inflammatory response with hemoadsorption may have positive impact on the endothelial glycocalix and also may be advantageous for maintenance of the vascular barrier function which plays a pivotal role in the development of tissue edema and oxygen mismatch. Hemoadsorption therapy seems to offer a promising new option for the treatment of patients with overwhelming inflammatory response leading to faster hemodynamic and metabolic stabilization finally resulting in preserved organ functions.