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.

[Postoperative acute mitral regurgitation. Unexpected finding after minor non-cardiac surgery]. / Akute perioperative Mitralklappeninsuffizienz. Unerwarteter Befund nach nichtkardiochirurgischem Bagatelleingriff.

This report describes the case of a 59-year-old man who was scheduled for general anesthesia with propofol, sufentanil and sevoflurane for removal of a metal implant. The patient was classified as American Society of Anesthesiologists (ASA) II status because of an asymptomatic mitral valve prolapse and medically treated arterial hypertension. During induction of narcosis a pulsoxymetrically measured inadequate increase in oxygen saturation after preoxygenation was noticed and a moderate respiratory obstruction occurred intraoperatively, but anesthesia was uneventfully completed and the patient was extubated. However, 3 h later the patient developed severe dyspnea, hypoxia, tachycardia and arterial hypotension. Physical examination revealed a new grade 4/6 systolic murmur radiating to the axilla and X-ray showed bilateral pulmonary edema. Neither electrocardiographic nor biochemical manifestations of acute myocardial infarction were identified but transthoracic echocardiography revealed fluttering of the posterior leaflet of the mitral valve with grade III regurgitation and dilation of the left atrium. Coronary angiography was normal and left ventriculography confirmed severe mitral regurgitation. Mitral valve repair was successfully performed 22 h after presentation of symptoms. Mitral regurgitation is a common finding on echocardiography, seen to some degree in over 75% of the population. The etiology of mitral valve insufficiency which can be caused by pathologic changes of one or more of the components of the mitral valve, including the leaflets, annulus, chordae tendineae, papillary muscles, or by abnormalities of the surrounding left ventricle and/or atrium are discussed. Rupture of mitral chordae tendineae is infrequent and causes acute hemodynamic deterioration and needs corrective surgery. Valve replacement should be performed only if mitral valve repair is not possible. Echocardiography is an invaluable tool in determining the severity of regurgitation, the integrity of the mitral valve apparatus, the extent of left ventricular enlargement, and the ejection fraction. Acute mitral valve regurgitation caused by a rupture of chordae tendineae should be considered in the differential diagnosis of perioperative acute pulmonary edema.

Interdisciplinary Peripartum Management of Acute Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation - a Case Report and Literature Review.

Extracorporeal membrane oxygenation (ECMO) is increasingly used for the management of acute severe cardiac and respiratory failure. One of the indications is acute respiratory distress syndrome (ARDS) for which, in some severe cases, ECMO represents the only possibility to save lives. We report on the successful long-term use of ECMO in a postpartum patient with recurrent pulmonary decompensation after peripartum uterine rupture with extensive blood loss.

Effects of carbon dioxide pneumoperitoneum on cerebral hemodynamics in pigs.

Previous studies have shown that laparoscopic interventions are associated with increases in intracranial pressure. However, the consequences on cerebral blood flow (CBF) are unknown. This study investigates the effects of carbon dioxide (CO2) pneumoperitoneum on CBF in pigs. Ten pigs (weight, 20-26 kg) were anesthetized with 1.4% isoflurane and fentanyl (1 microg/kg per minute). Mechanical ventilation (fraction of inspired oxygen = 0.4) was set to maintain normocapnia (end-tidal CO2 tension = 35 mm Hg). Arterial and central venous catheters were placed for measurement of mean arterial blood pressure and central venous pressure. Bilateral internal carotid artery blood flow was measured using two transient time flow probes placed around both carotid arteries (with ligated external carotid arteries). Cortical and subcortical cerebral blood flow was measured using laser Doppler flowmetry. Sagittal sinus pressure was measured via a superior sagittal sinus catheter. After baseline measurements, the peritoneal cavity of the animals was insufflated with CO2 to achieve an intraabdominal pressure of 12-mm Hg. After 10 minutes of stable CO2, pneumoperitoneum measurements were repeated. Increases in central venous pressure (6.3 +/- 2.1 to 11.1 +/- 3.0 mm Hg) and sagittal sinus pressure (8.0 +/- 2.8 to 11.9 +/- 3.0 mm Hg) were noted during CO2 pneumoperitoneum (P < .05). Bilateral internal carotid artery blood flow (46.0 +/- 7.4 vs 47.7 +/- 7.1 mL/100g per minute), cortical CBF (263 +/- 115 vs 259 +/- 158 tissue perfusion units), and subcortical CBF (131 +/- 145 vs 133 +/- 149 tissue perfusion units) did not change during CO2 pneumoperitoneum. The current data show that CO2 pneumoperitoneum increases sagittal sinus pressure without changing CBF. Increases in sagittal sinus pressure are likely related to decreases in cerebral venous drainage caused by increases in intraabdominal pressure.

[Septic encephalopathy]. / Die septische Enzephalopathie.

Impaired mental function, from clouding of consciousness to deep coma is often seen in patients with systemic inflammation. Diagnosis of this syndrome which is called "septic encephalopathy" is dependent on exclusion of other causes. The underlying mechanisms have only been defined in parts. The appearance of cerebral symptoms during an infection increases mortality. Primary symptoms of septic encephalopathy appear early, before other septic organ manifestations become apparent. The most sensible parameter for diagnosis of septic encephalopathy in comatose patients or under sedation is the EEG. It shows general alterations which increase parallelly to the severity of septic encephalopathy. Septic encephalopathy has to be considered a multifactorial event. In an early stage of the development of septic encephalopathy, bacteremia induces overproduction of cytokines and other mediators. This causes metabolic dysregulation with effects on the cerebral protein-, glucose and neurotransmitter metabolism. In addition, cytokines damage the blood-brain-barrier and exert direct cytotoxic effects. This results in histologic detectable neuronal damage. Further effects of the cytokine expression are perivascular edema and hemorrhage. The loss of metabolic regulation of the brain perfusion and local cerebral ischemia additionally contribute to the etiology of septic encephalopathy. A specific therapy is not yet known.

Changes in instrumentally and classically conditioned limb-flexion responses following inferior olivary lesions and olivocerebellar tractotomy in the cat.

Lesions were placed in various parts of the inferior olivary nucleus and olivocerebellar tract in an attempt to define further the role of the inferior olive in the performance of a conditioned limb-flexion response (LFR) in cats. Thirty-two cats were trained to make an LFR using either classical or instrumental conditioning. The conditioned stimulus (CS) was a tone, and the unconditioned stimulus (US), a shock to the forelimb. Following training, lesions were placed in various parts of the inferior olivary nucleus in 20 animals (radio frequency lesions, 17; electrolytic lesions, 3). Midline section of the olivocerebellar tract was carried out in 12 animals. The degree of conditioned-response (CR) loss resulting from a given lesion was closely related to the precise locus of the lesion. Rostromedial olivary lesions, which included the spino- and cortico-olivary forelimb projection zones and the olivocerebellar projection area, resulted in varying degrees of CR loss (from partial to near total), deregulation of response latency, and a significant reduction of response amplitude. The CR deficit and degree of post-operative CR recovery were directly related to the extent of damage to this part of the rostromedial olive. Lesions restricted to the caudal olive or to caudal levels of the olivo-cerebellar tract resulted in no postoperative CR deficits. Animals with caudal lesions, however, showed more severe general motor deficits postoperatively than did those with rostromedial lesions and loss of the CR. Prolonged training of animals with the most complete CR deficits resulted in some relearning, but response patterns were typified by long-latency, low-amplitude CRs and a highly unstable response pattern.

Effects of xenon on mesenteric blood flow.

BACKGROUND AND OBJECTIVE: The effects of xenon on mesenteric vascular resistance have not been investigated. Because human beings anaesthetized with xenon show good cardiovascular stability, we believed that the agent would have little or no effect on vascular resistance in the splanchnic bed. We determined the effects of different inhaled xenon concentrations on mesenteric blood flow and mesenteric oxygen consumption in pigs sedated with intravenous propofol. METHODS: Twenty-three minipigs were instrumented with transit time flow probes around the pulmonary and superior mesenteric arteries as well as with pulmonary artery and portal venous catheters. A 14 h recovery was allowed followed by recordings of baseline values. Xenon was then randomly administered in 0.30, 0.50, and 0.70 end-tidal fractions. RESULTS: The administration of xenon resulted in an 8% (not dose dependent) decrease in mean arterial pressure (from 99 +/- 15 to 91 +/- 19 mmHg; P < 0.05), a 20% decrease in calculated systemic oxygen consumption (from 0.23 +/- 0.07 to 0.19 +/- 0.04L min(-1); P < 0.01), a 20% reduction in mesenteric oxygen delivery (from 41 +/- 12 to 33 +/- 11 mL min; P < 0.001), a 37% reduction in mesentericmetabolic rate of oxygen (from 11.3 +/- 3.6 to 7.1 +/- 3.2 mL min(-1); P < 0.01) and an 8% decrease in mesenteric artery blood flow (0.22 +/- 0.07 to 0.20 +/- 0.07 L min(-1); P < 0.05) in a dose-dependent fashion. Heart rate, cardiac output, systemic vascular resistance, mesenteric vascular resistance, mesenteric oxygen extraction fraction and portal lactate concentration were not significantly altered by xenon. CONCLUSIONS: Xenon inhalation in the propofol-sedated pig had no measurable effects on mesenteric vascular resistance. This finding may partly explain the well-known cardiovascular stability observed in patients anaesthetized with xenon. Although mesenteric artery blood flow and mesenteric oxygen delivery decreased during xenon administration, unchanged mesenteric oxygen extraction fraction and portal lactate suggest that metabolic regulation of the splanchnic circulation remained unaltered.

Cerebral histopathology following portal venous infusion of bacteria in a chronic porcine model.

BACKGROUND: The aim of this study was to histologically investigate brain damage after prolonged periods of bacteremia in pigs. METHODS: Twenty-one pathogen-free Göttingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through midline abdominal incision with a portal venous catheter. After craniotomy the superior sagittal sinus was cannulated. A lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid. Twelve hours after instrumentation, the animals were randomized in two groups: septic and control animals. The septic group received an infusion of 107 colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous catheter each day. The control group received saline. Postoperative intensive care treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and processed for histology. Each pathologic alteration found in the samples was assessed and given a severity code (0-3). RESULTS: Sham-operated animals showed no alterations caused by the instrumentation and the intensive care treatment. The septic group showed typical clinical signs of sepsis. Vasopressor support and mechanical ventilation prevented systemic hypotension and hypoxemia. High serum and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha were detected. The septic group showed severe histologic abnormalities of the brain including perivascular edema, spongiform degeneration, hyperemia, and purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken nuclei, and disintegration of the nuclear membrane. CONCLUSIONS: Abdominal sepsis induced severe brain damage that was not related to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.

Effects of xenon on cerebral blood flow and cerebral glucose utilization in rats.

BACKGROUND: The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography. METHODS: Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only. RESULTS: Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon. CONCLUSION: Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.

Effects of xenon on cerebral blood flow and autoregulation: an experimental study in pigs.

We have investigated the effects of xenon on regional cerebral blood flow (rCBF) and autoregulation in pigs sedated with propofol 4 mg kg-1 h-1. Balloon-tipped catheters were placed into the descending aorta and inferior vena cava of 15 Göttingen Minipigs for manipulation of arterial pressure and blood sampling. rCBF was measured using the sagittal sinus outflow technique. Xenon was adjusted randomly to end-tidal fractions (FE'Xe) of 0, 0.30, 0.50 and 0.70. After baseline measurements of heart rate (HR), mean arterial pressure (MAP), rCBF, sagittal sinus pressure (SSP) and calculation of regional cerebrovascular resistance (rCVR) at each respective FE'Xe, autoregulation was tested in the MAP range 60-120 mm Hg. Increasing FE'Xe had no effect on HR, MAP, rCBF or SSP. rCVR increased with increases in MAP, regardless of FE'Xe. Autoregulation was not impaired. We conclude that xenon inhalation had no effect on rCBF and autoregulation in our model, which could suggest that xenon is an adequate adjunct for neurosurgical anaesthesia.

[Visceral resorption of intra-abdominal insufflated carbon dioxide in swine]. / Viszerale Resorption von intraabdominell insuffliertem Kohlendioxid beim Schwein.

OBJECTIVES: Total intraperitoneal carbon dioxide (CO2) resorption from CO2-pneumoperitoneum increases in relation to intraabdominal pressure (IAP) up to an upper limit of 10 to 15 mmHg. The purpose of this prospective study was to evaluate the visceral fraction of CO2 resorption in comparison to total intraperitoneal CO2 resorption in pigs to address possible reasons for this upper limit. METHODS: 16 pigs were chronically instrumented. Via midline laparotomy, a transit-time ultrasound flow probe was placed around the portal vein for continuous recording of the portal venous blood flow and a catheter was inserted into the portal vein via lienal vein. After complete recovery (7-10 days), animals were anesthetized with propofol and fentanyl and a pulmonary artery, a hepatic venous, an arterial, and an intraabdominal insufflation catheter were inserted. Mechanical ventilation (O2/air; FiO2 = 0.4) was adjusted to maintain endtidal CO2 at 34 to 36 mmHg using an Engstrøm Elvira ventilator. After an equilibration period of 3h, CO2, (n = 8) or air (n = 8) was insufflated. IAP was increased in steps of 4 mmHg and maintained constant at each respective IAP-level for 20 min. Blood gas analyses were assessed from portal venous, hepatic venous, central venous, and arterial probes at each IAP-level. Total intraperitoneal CO2 resorption was calculated from parameters derived from indirect calorimetry, the portal venous fraction from blood gas values and the portal venous blood flow following Fick's principle. Data were analyzed using Friedman's test. RESULTS: Total CO2 resorption increased continuously with rising IAP. Highest values were measured at IAP = 16 mmHg with 84 (74-93) ml/min. A further increase of IAP resulted in a significant decrease of total CO2 resorption. The visceral fraction of intraperitoneal CO2 resorption increased up to 28 (17-36) ml/min at IAP = 12 mmHg. Portal venous blood flow was also elevated or unchanged up to this IAP. At IAP = 20 mmHg or IAP = 24 mmHg portal venous blood flow decreased (79% of baseline) and in consequence portal venous calculated fraction of intraperitoneal carbon dioxide resorption decreased to 14 (8-20) ml/min. 20 min after desufflation, intraabdominal CO2 resorption was completed. With air insufflation, all parameters of CO2 balance were unchanged. DISCUSSION: The IAP dependent increase in CO2 resorption is limited due to an IAP related occlusion of the peritoneal capillaries and the limited expansion of peritoneal diffusion area. In this model, it was possible to show that visceral fraction is about one third of the total intraperitoneal carbon dioxide resorption and that this fraction depends on portal venous blood flow. Thus, a decrease in total CO2 resorption may indicate a reduction in portal venous blood flow.

Effects of intraabdominally insufflated carbon dioxide and elevated intraabdominal pressure on splanchnic circulation: an experimental study in pigs.

BACKGROUND: Intraabdominally insufflated carbon dioxide (CO2) during laparoscopy may have a specific effect on splanchnic circulation that may be unrelated to the effects of increased intraabdominal pressure alone. Therefore, the influences of insufflation with CO2 versus air on splanchnic circulation were compared. METHODS: Pigs were chronically instrumented for continuous recording of mesenteric artery, portal venous, inferior vena cava, and pulmonary arterial blood flow and portal venous pressure. After induction of anesthesia, CO2 or air was insufflated in 14 and 10 pigs, respectively. With the pigs in the supine position, intraabdominal pressure was increased in steps of 4 mmHg up to 24 mmHg by graded gas insufflation. RESULTS: During air insufflation, mesenteric artery vascular resistance was unchanged, whereas mesenteric arterial blood flow decreased with increasing intraabdominal pressure. Shortly after CO2 insufflation to an intraabdominal pressure of 4 mmHg, mean arterial pressure, mesenteric arterial blood flow, and mesenteric arterial vascular resistance were increased by 21%, 12% and 9%, respectively. Subsequently, with the onset of CO2 resorption in the third minute, mean arterial pressure declined to baseline values and mesenteric arterial vascular resistance declined to 85% of baseline values, whereas mesenteric arterial blood flow continued to increase to a maximum of 24% higher than baseline values. At steady-state conditions during CO2 insufflation, mesenteric arterial blood flow was increased up to an intraabdominal pressure 16 mmHg but decreased at higher intraabdominal pressures. CONCLUSIONS: In contrast to air insufflation, intraabdominal insufflation of CO2 resulted in a moderate splanchnic hyperemia at an intraabdominal pressure < or = 12 mmHg. At higher intraabdominal pressure values, pressure-induced changes became more important than the type of gas used.

Inflammatory liver disease shortens atracurium-induced neuromuscular blockade in rats.

BACKGROUND: and objective Inflammatory liver dysfunction in rats leads to a prolonged vecuronium-induced neuromuscular blockade due to insufficient metabolism. A coexisting resistance against the drug partly counteracts this prolongation. The present study investigates the pharmacodynamics of atracurium whose metabolism does not depend on liver function. METHODS: Male Sprague-Dawley rats (n=14; 290 +/- 30 g) were randomly allocated to either a group in which liver inflammation was induced by intravenous injection of 60 mg kg(-1) heat-killed Corynebacterium parvum or to a control group. On day 5 after injection, liver function was assessed using the aminopyrine breath test. Under propofol anaesthesia, duration of action of atracurium (4.8 mg kg(-1)) was measured by evoked mechanomyography (stimulation of the sciatic nerve; contraction of the gastrocnemius muscle). Nitric oxide concentrations, as variables for the severity of the inflammation, were assessed by measurement of nitrite/nitrate plasma concentrations. RESULTS: In C. parvum-injected rats, nitrite/nitrate plasma concentrations were increased (972 +/- 597 vs. 25 +/- 7 micromol L(-1)), the aminopyrine turnover was depressed (1.7 +/- 0.4% vs. 3.5 +/- 0.5%), and the atracurium-induced neuromuscular blockade was shortened (372 +/- 128 s vs. 1081 +/- 234 s). CONCLUSIONS: A systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to atracurium. Further investigations are needed regarding a possible up-regulation of acetylcholine receptors or an increased protein binding of atracurium during sepsis to clarify reasons behind this phenomenon.