[Managing the pandemic-relocation concept for COVID-19 intensive care patients and non-COVID-19 intensive care patients in Baden-Württemberg]. / Die Pandemie bewältigen ­ Verlegungskonzept von COVID-19-Intensivpatienten und Non-COVID-19-Intensivpatienten in Baden-Württemberg.

BACKGROUND: A sharp rise in COVID-19 infections threatened to lead to a local overload of intensive care units in autumn 2020. To prevent this scenario a nationwide relocation concept was developed. METHODS: For the development of the concept publicly available infection rates of the leading infection authority in Germany were used. Within this concept six medical care regions (clusters) were designed around a center of maximum intensive care (ECMO option) based on the number of intensive care beds per 100,000 inhabitants. The concept describes the management structure including a structural chart, the individual tasks, the organization and the cluster assignment of the clinics. The transfers of intensive care patients within and between the clusters were recorded from 11 December 2020 to 31 January 2021. RESULT: In Germany and Baden-Württemberg, 1.5% of patients newly infected with SARS-CoV­2 required intensive care treatment in mid-December 2020. With a 7-day incidence of 192 new infections in Germany, the hospitalization rate was 10% and 28-35% of the intensive care beds were occupied by COVID-19 patients. Only 16.8% of the intensive care beds were still available, in contrast to 35% in June 2020. The developed relocation concept has been in use in Baden-Württemberg starting from 10 December 2020. From then until 7 February 2021, a median of 24 ± 5/54 intensive care patients were transferred within the individual clusters, in total 154 intensive care patients. Between the clusters, a minimum of 1 and a maximum of 15 (median 12.5) patients were transferred, 21 intensive care patients were transferred to other federal states and 21 intensive care patients were admitted from these states. The total number of intensive care patients transferred was 261. CONCLUSION: If the number of infections with SARS-CoV­2 increases, a nationwide relocation concept for COVID-19 intensive care patients and non-COVID-19 intensive care patients should be installed at an early stage in order not to overwhelm the capacities of hospitals. Supply regions around a leading clinic with maximum intensive care options are to be defined with a central management that organizes the necessary relocations in cooperation with regional and superregional rescue service control centers. With this concept and the intensive care transports carried out, it was possible to effectively prevent the overload of individual clinics with COVID-19 patients in Baden-Württemberg. Due to that an almost unchanged number of patients requiring regular intensive care could be treated.

The JAK1/2 inhibitor ruxolitinib in patients with COVID-19 triggered hyperinflammation: the RuxCoFlam trial.

Dysregulated hyperinflammatory response is key in the pathogenesis in patients with severe COVID-19 leading to acute respiratory distress syndrome and multiorgan failure. Whilst immunosuppression has been proven to be effective, potential biological targets and optimal timing of treatment are still conflicting. We sought to evaluate efficacy and safety of the Janus Kinase 1/2 inhibitor ruxolitinib, employing the previously developed COVID-19 Inflammation Score (CIS) in a prospective multicenter open label phase II trial (NCT04338958). Primary objective was reversal of hyperinflammation (CIS reduction of ≥25% at day 7 in ≥20% of patients). In 184 patients with a CIS of ≥10 (median 12) ruxolitinib was commenced at an initial dose of 10 mg twice daily and applied over a median of 14 days (range, 2-31). On day 7, median CIS declined to 6 (range, 1-13); 71% of patients (CI 64-77%) achieved a ≥25% CIS reduction accompanied by a reduction of markers of inflammation. Median cumulative dose was 272.5 mg/d. Treatment was well tolerated without any grade 3-5 adverse events related to ruxolitinib. Forty-four patients (23.9%) died, all without reported association to study drug. In conclusion, ruxolitinib proved to be safe and effective in a cohort of COVID-19 patients with defined hyperinflammation.

International registry on the use of the CytoSorb® adsorber in ICU patients : Study protocol and preliminary results.

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.

Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs.

We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glycerol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.

Effects of selective iNOS inhibition on gut and liver O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

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.

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.

Effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX-30 on intestinal O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

Sepsis may lead to deranged thromboxane-prostacyclin ratio with consecutive organ dysfunction. Because of the suggested role of the gut in the pathogenesis of septic shock and multiple organ failure, we investigated the effects of the novel dual thromboxane synthase inhibitor and receptor antagonist DTTX-30 (TRASI) on intestinal tissue perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxemia. Before, 12, 18, and 24 h after starting continuous i.v. endotoxin (LPS), we measured portal venous (PV) blood flow, intestinal oxygen extraction (iO2ER), intracapillary hemoglobin O2 saturation (HbO2%) of the ileal wall, intramucosal ileal PCO2, PV lactate-pyruvate (L-P) ratio, and plasma levels of thromboxane and prostacyclin. Treatment with TRASI (0.12 mg/kg i.v. bolus injection followed by an infusion of 0.29 mg/kg/h) initiated after 12 h of LPS infusion markedly reduced the plasma thromboxane levels and attenuated the LPS-induced fall in systemic vascular resistance, resulting in hemodynamic stabilization. TRASI did not influence the LPS-induced increase in PV blood flow nor intracapillary HbO2%, thus reflecting unchanged microcirculatory O2 availability and decreased iO2ER, possibly because of reduced O2 requirements. Nevertheless, TRASI prevented the LPS-induced increase in the PV L-P ratio, attenuated the progression of the ileal mucosal-arterial PCO2 gap, and tended to attenuate the gradual fall of PV pH. Hence, compounds like TRASI may beneficially influence LPS-related derangements of gut energy metabolism.

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

OBJECTIVE: To 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. DESIGN: Descriptive laboratory investigation. SUBJECTS: 7 volunteers. INTERVENTION: Primed 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 microgram/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 RESULTS: Glucose production increased from 14.1 +/- 1.2 to 21.5 +/- 2.0 mumol/kg/min (p < 0.05) after 80 min of adrenergic stimulation and then decreased again to 17.9 +/- 1.2 mumol/kg/min after 240 min. Leucine and ketoisocaproate (KIC) fluxes were 2.3 +/- 0.2 and 2.6 +/- 0.2 mumol/kg/min, respectively, at baseline and gradually decreased to 1.8 +/- 0.2 and 2.2 +/- 0.1 mumol/kg/min, respectively, after 240 min of adrenaline infusion (both p < 0.05). Alanine flux increased from 3.7 +/- 0.5 to 6.9 +/- 0.9 mumol/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 mumol/kg/min during adrenaline (p < 0.05). CONCLUSIONS: Adrenaline 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.

Is it feasible to monitor total hepatic blood flow by use of transesophageal echography? An experimental study in pigs.

OBJECTIVES: Total hepatic venous blood flow is determined by the common hepatic arterial blood flow and the venous outflow from stomach, spleen, pancreas, small intestine, and bowel, collected by the portal vein, and thus represents overall splanchnic perfusion. We investigated whether transesophageal echography (TEE) can provide a method for bedside assessment of hepatic venous blood flow useful as a noninvasive method for measuring splanchnic perfusion in clinical practice. DESIGN AND SETTING: Experimental study in 15 anesthetized and ventilated pigs in an animal research laboratory. INTERVENTIONS: TEE-derived calculations of hepatic venous blood flow were compared with liver blood flow measurements using perivascular ultrasound flow probes surgically positioned on portal vein and common hepatic artery. Parameters were determined at baseline and after modulating splanchnic perfusion by either PEEP maneuver (15 cmH2O) or intravenous epinephrine (0.1 microgram kg-1 min-1). MEASUREMENTS AND RESULTS: Diameter (d) and velocity time integral (VTI) of all three hepatic veins were determined by TEE, heart rate (HR) was derived from electrocardiography and flow subsequently calculated as Q = pi.(d/2)(2).0.57.VTI.HR. Regression analysis of matched TEE and flow probe values showed a significant linear relationship (r2 = 0.698). Bias analysis revealed a systematic underestimation of liver blood flow by TEE, possibly due to use of 0.57 as correction factor for mean velocity, while changes in liver blood flow were reliably detected. CONCLUSION: TEE offers a noninvasive approach for monitoring hepatic perfusion and may be used in patients.

Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia.

OBJECTIVE: To investigate the effects of nicotinamide (NIC), an inhibitor of poly(ADP-ribose) synthetase (PARS), on intestinal and liver perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Animal laboratory in a university hospital. SUBJECTS: Sixteen pigs, divided into two groups: nine endotoxemic animals without therapy (CON); seven animals treated with NIC. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia continuous i.v. infusion of NIC (10 mg/kg per hour) was administered until the end of the experiment. MEASUREMENTS AND RESULTS: All animals developed hyperdynamic circulation with sustained increase in cardiac output and progressive fall in mean arterial pressure. NIC maintained blood pressure without affecting CO. Hepato-splanchnic macrocirculation was not modified by the treatment. Nevertheless, although NIC attenuated the progressive rise of ileal mucosal-arterial PCO2 gap, it failed to improve portal venous L/P ratio, a marker of the overall energy state of the portal venous drained viscera. Similarly, neither the increased hepatic venous L/P ratio nor the simultaneous drop in hepatic lactate uptake were influenced by NIC. CONCLUSIONS: Although NIC maintained hemodynamic stabilization during long-term endotoxemia, it was unable to improve LPS-induced deterioration of the hepato-splanchnic energy metabolism. More potent and selective PARS inhibitors are needed to elucidate the role of a PARS-dependent pathway in a clinically relevant models of sepsis.

Hepatic O2 exchange and liver energy metabolism in hyperdynamic porcine endotoxemia: effects of iloprost.

OBJECTIVE: To compare the effects of a 12 h continuous infusion of iloprost, a stable prostacyclin analogue, on hepatic blood flow (Qliv), O2 exchange, and energy metabolism during a 24 h hyperdynamic, porcine endotoxemia with volume resuscitation alone. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-eight domestic pigs: 16 animals during endotoxemia with volume resuscitation alone (ETX), 12 with endotoxemia, volume resuscitation, and treatment with iloprost (ILO). INTERVENTIONS: Endotoxemia was initiated by continuous infusion of E. coli lipopolysaccharide. Animals were resuscitated with hetastarch, aimed at maintaining a MAP of > 60 mmHg. After 12 h of endotoxemia, iloprost was administered for 12 h in the treatment group, titrated to avoid pharmacologically induced hypotension (MAP < 60 mmHg). MEASUREMENTS AND RESULTS: Iloprost significantly increased Qliv, with no effect on hepatic O2 delivery. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface, as well as HbScO2 frequency distributions--a measure of microcirculatory O2 availability--remained unchanged. Treatment with iloprost, however, significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased endogenous glucose production (EGP) rate, iloprost restored EGP to normal at the end of the experiment. CONCLUSIONS: Thus, in a clinically relevant model of human sepsis, iloprost did not produce potential adverse effects but rather ameliorated hepatic metabolic disturbances and, thereby, hepatic energy balance.

Increased ileal-mucosal-arterial PCO2 gap is associated with impaired villus microcirculation in endotoxic pigs.

OBJECTIVE: To investigate whether an increased ileal-mucosal-arterial PCO2 gap (delta PCO2) during hyperdynamic porcine endotoxemia is associated with impaired villus microcirculation. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal research laboratory. ANIMALS: Twenty-two domestic pigs. INTERVENTIONS: After baseline measurements, anesthetized and ventilated pigs received continuous i.v. endotoxin (ETX, n = 12) for 24 h or placebo (SHAM, n = 10). MEASUREMENTS AND RESULTS: Before, as well as 12 and 24 h after, the start of endotoxin or saline portal venous blood flow (QPV, ultrasound flow probe) and lactate/pyruvate ratios (L/P), the ileal-mucosal-arterial delta PCO2 (fiberoptic sensor) and bowel-wall capillary hemoglobin O2 saturation (%Hb-O2-cap, remission spectrophotometry) were assessed together with intravital video records of the ileal-mucosal microcirculation (number of perfused/heterogeneously perfused/unperfused villi) using orthogonal polarization spectral imaging (CYTOSCAN A/R) via an ileostomy. At 12 and 24 h endotoxin infusion, about half of the evaluated villi were heterogeneously or unperfused which was paralleled by a progressive significant increase of the ileal-mucosal-arterial delta PCO2 and portal venous L/P ratios, whereas QPV as well as both the mean %Hb-O2-cap and the %Hb-O2-cap frequency distributions remained unchanged. By contrast, in the SHAM-group, mucosal microcirculation was well-preserved, and none of the other parameters were influenced. CONCLUSIONS: We conclude that an increased ileal-mucosal-arterial delta PCO2 during porcine endotoxemia is related to impaired villus microcirculation. A putative contribution of disturbed cellular oxygen utilization resulting from "cytopathic hypoxia" may also assume importance.

Hepatic oxygen exchange and energy metabolism in hyperdynamic porcine endotoxemia: effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX30.

OBJECTIVE: We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30. INTERVENTIONS: Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg-1 followed by 12 h continuous infusion of 0.29 mg kg-1 per h. MEASUREMENTS AND RESULTS: DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1 alpha with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well. CONCLUSIONS: DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance.

Effects of xylitol on carbohydrate and protein metabolism after trauma and during sepsis.

INTRODUCTION: Total parenteral nutrition (TPN) after trauma and during sepsis has two major goals. One is the reduction of increased protein catabolism, the second is to avoid hyperglycemia and enhanced hepatic gluconeogenesis. Glucose and xylitol differ in their utilization rates after trauma and during sepsis. Whole-body glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects on hepatic glucose production and protein sparing, we conducted two animal and two clinical studies. METHODS: For the analysis of glucose and protein turnover radioactive and stable isotope techniques were applied. In burned rats primed constant infusions of 6-[3H]-glucose, 1-[14C]-alanine, 3-[14C]-alanine and U-[14C]-acetate were used to determine whole body glucose turnover, gluconeogenesis from C3-precursors and alanine flux. In septic rats nitrogen balance was calculated after determination of 24-hour-urine nitrogen content measured by micro-Kjeldahl digestion. 24-hour urinary 3-methyl-histidine excretion was analysed by amino acid autoanalyser. In human studies hepatic glucose production and urea synthesis rates were measured using primed continuous infusions of [6,6-d2]-glucose and [2-N15]-urea, respectively. RESULTS: In the first trauma model we demonstrated that hypocaloric xylitol in contrast to glucose significantly reduced hepatic glucose production and gluconeogenesis from C3-carbons. In the septic rat exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated nitrogen retention and lower 3-methyl-histidine excretion. In two studies on surgical intensive care patients we were able to confirm these nitrogen sparing properties of xylitol. Hepatic glucose production and urea synthesis rates were significantly reduced during xylitol infusion after trauma, whereas equicaloric glucose had no effects. In septic patients xylitol led to significant lower lactate concentrations and gluconeogenesis rates than isocaloric glucose. DISCUSSION: In animal as well as in human studies hypocaloric xylitol and the mixture of glucose/xylitol (1:1) were more efficient in preserving body protein than glucose alone. Hepatic gluconeogenesis was significantly reduced when compared to isocaloric glucose. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg BW/d by xylitol. During long-term TPN a glucose/xylitol mixture (1:1) in a dosage of 6 g/kg BW/d is recommended together with amino acids and, if necessary, lipids.

Catecholamines in the treatment of septic shock: effects beyond perfusion.

OBJECTIVE: To review the metabolic effects of sympathomimetic agents in the septic patient. DATA SOURCES: A review of articles reported on the metabolic effects of the commonly used sympatho-mimetic agents in the critically ill patient. SUMMARY OF REVIEW: Sepsis and septic shock are clinically charcterized mainly by derangements of cardiocirculatory function. Mainstay therapeutic interventions for haemodynamic stabilisation are adequate volume resuscitation and vasoactive agents. These, however, may be linked with additional effects on energy balance and cell metabolism. As well as the haemodynamic effects, specific metabolic effects need to be considered for optimal vasopressor treatment during severe sepsis and septic shock. This review highlights the typical haemodynamic and metabolic alterations associated with the commonly used sympathomimetic drugs in these conditions. CONCLUSIONS: Sepsis and septic shock are linked with profound metabolic alterations. An additional impact of vasoactive therapy on metabolism has to be taken into account when using these agents to treat severe sepsis and septic shock.

[Gastric mucosal tonometry: more than splanchnic circulation and oxygenics]. / Magenmukosa-Tonometrie: Mehr als Splanchnikusperfusion und Sauerstoffkinetik.

The tonometric measurement of the arterial-intramucosal PCO2-difference and the calculation of the intramucosal pH is currently the only parameter which is available in the clinical routine for the assessment of perfusion, oxygen kinetics and metabolic activity of the patho-splanchnic region. Since this region with its unique both parallel and serial blood supply net comprises several organs with different metabolic performance, among which moreover the synthetic activity of the liver has to be taken into account, tonometric data have to be interpreted independently from blood flow and oxygen transport and uptake in this region. In fact, tonometry is an integrative parameter for perfusion, oxygenation and cellular energy balance. Therefore, it more completely reflects the complex anatomical and physiological conditions.

[Changes in various metabolic parameters following bloodletting]. / Veränderungen verschiedener Stoffwechselumsätze nach Aderlass.

OBJECTIVE: We investigated hypovolaemia induced by bloodletting, accompanied by statistically significant, but clinically irrelevant increase of heart rate together with unchanged blood pressure, with regard to hepatic glucose production as well as alanine and glycerol turnover rates. METHODS: Healthy male volunteers (n = 18) were bled 15 ml/kg body weight over 20 min and remained hypovolaemic for 60 minutes. Heart rate was recorded by ECG and blood pressure by an oscillometric device. Before and after bloodletting hepatic glucose production as well as alanine and glycerol turnover rates were determined using the stable isotopes 6.6-D2-glucose, 15N-alanine and D5-glycerol as tracers. Simultaneously, the blood concentrations of adrenaline, noradrenaline, free fatty acids and glycerol were measured. RESULTS: Bleeding did not change the mean arterial blood pressure, but increased the heart rate significantly from 61 +/- 9 to 70 +/- 13 1/ min. Noradrenaline levels increased significantly from 1.16 +/- 0.41 to 2.15 +/- 0.69 nmol/l. Hepatic glucose production (HGP) as well as alanine (AlaTO) and glycerol turnover (GlyTO) decreased significantly during hypovolaemia. HGP fell from 2.72 +/- 0.29 to 2.56 +/- 0.28 mg/kg/min, AlaTO from 0.71 +/- 0.27 to 0.53 +/- 0.25 mg/kg/min and GlyTO from 4.9 +/- 2.1 to 3.8 +/- 1.4 mumol/kg/min, respectively. The blood levels of adrenaline, free fatty acids and glycerol did not change during the study. DISCUSSION: In respect of clinical signs, the cardiovascular status of the volunteers was stable after bleeding. In contrast, the decrease of HGP as well as the drop in alanine and glycerol turnover rates might be interpreted as a sign of an altered functional status of single organs, induced by changes of regional perfusion.