[Ventilation as a trigger for organ dysfunction and sepsis]. / Beatmung als Trigger für Organdysfunktion und Sepsis.

Both in the intensive care setting and during surgery, mechanical ventilation plays an important role in the treatment of critically ill patients with lung injury, but also in lung healthy patients. Mechanical ventilation is noncurative and is accompanied by various severe side effects. It is hypothesized that multiorgan failure can be induced by mechanical ventilation. Furthermore, there is evidence to suggest cross-talk between lungs and other organs. In particular, the activation of specific cells and cell programs in peripheral organs is an important step on the way to multiorgan failure. In addition to bidirectional connection between the lung and brain, nonprotective ventilation leads to cell apoptosis in the kidney and intestine and leads to an increase of biomarkers for organ dysfunction. It is believed that both inflammation mediators and pro-apoptotic factors are responsible for organ dysfunction.

Lateral prefrontal model-based signatures are reduced in healthy individuals with high trait impulsivity.

High impulsivity is an important risk factor for addiction with evidence from endophenotype studies. In addiction, behavioral control is shifted toward the habitual end. Habitual control can be described by retrospective updating of reward expectations in 'model-free' temporal-difference algorithms. Goal-directed control relies on the prospective consideration of actions and their outcomes, which can be captured by forward-planning 'model-based' algorithms. So far, no studies have examined behavioral and neural signatures of model-free and model-based control in healthy high-impulsive individuals. Fifty healthy participants were drawn from the upper and lower ends of 452 individuals, completing the Barratt Impulsiveness Scale. All participants performed a sequential decision-making task during functional magnetic resonance imaging (fMRI) and underwent structural MRI. Behavioral and fMRI data were analyzed by means of computational algorithms reflecting model-free and model-based control. Both groups did not differ regarding the balance of model-free and model-based control, but high-impulsive individuals showed a subtle but significant accentuation of model-free control alone. Right lateral prefrontal model-based signatures were reduced in high-impulsive individuals. Effects of smoking, drinking, general cognition or gray matter density did not account for the findings. Irrespectively of impulsivity, gray matter density in the left dorsolateral prefrontal cortex was positively associated with model-based control. The present study supports the idea that high levels of impulsivity are accompanied by behavioral and neural signatures in favor of model-free behavioral control. Behavioral results in healthy high-impulsive individuals were qualitatively different to findings in patients with the same task. The predictive relevance of these results remains an important target for future longitudinal studies.

Positive end-expiratory pressure titration at bedside using electrical impedance tomography in post-operative cardiac surgery patients.

BACKGROUND: Post-operative positive end-expiratory pressure (PEEP) setting to minimize the risk of ventilator-associated lung injury is still controversial. Assessment of regional ventilation distribution by electrical impedance tomography (EIT) might be superior as compared with global parameters. The aim of this prospective observational study was to compare global dynamic compliance (CRS ) with different EIT indices during a short clinical applicable descending PEEP trial. METHODS: Twenty mechanically ventilated patients after elective cardiac surgery received a standard recruitment manoeuvre (RM) following descending PEEP trial in steps of 2 cmH2 O from PEEP 14 cmH2 O to 6 cmH2 O. During baseline and all PEEP steps, CRS was assessed and regional ventilation distribution was measured by means of EIT. The individual 'best' PEEP values for the derived EIT indices and CRS were calculated and compared. RESULTS: The descending PEEP trial lasted less than 10 min. CRS increased after the RM and showed a maximum value at PEEP 8 cmH2 O. Ventilation distribution shifted more to dependent lung regions after RM and back to more non-dependent regions during the PEEP trial. Individual 'best' PEEP by CRS showed significantly lower values than 'best' PEEP by ventilation distribution measured with EIT indices. CONCLUSION: During a short descending PEEP trial at bedside, EIT is capable of following the status of regional ventilation distribution in ventilated patients. The 'best' PEEP value identified by individual maximum CRS was lower than optimal PEEP levels as determined by means of EIT indices. EIT could help setting PEEP in post-operative ventilated patients.

Case report: practicability of functionally based tractography of the optic radiation during presurgical epilepsy work up.

Pre-operative tractography of the optic radiation (OR) has been advised to assess the risk for postoperative visual field deficit (VFD) in certain candidates for resective epilepsy surgery. Diffusion tensor imaging (DTI) tractography relies on a precise anatomical determination of start and target regions of interest (ROIs), such as the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The post-chiasmal visual pathway and V1 show considerable inter-individual variability, and in epilepsy patients parenchymatous lesions might further complicate this matter. A functionally based tractography (FBT) seems beneficial for precise OR identification. We assessed practicability of FBT for OR identification in a patient with occipital lobe epilepsy due to a temporo-occipital maldevelopmental tumor. The MRI protocol at 3T included a T1-weighted sagittal 3D scan, a T2-weighted axial 2D scan and a DTI scan using an echo planar spin echo sequence. ROIs for fiber tracking of OR (LGN & V1) were determined with T2*-weighted fMRI-based retinotopic assessment. After DTI pre-processing and fiber tracking, paths with similar properties were combined in clusters for visual presentation and OR localization. Retinotopic phase maps allowed for the identification of V1 and LGN for a precise DTI-based reconstruction of OR, which was distant to the patient's tumor. Location and structure of ORs were comparable in each hemisphere. FBT could thus influence the human research of the extrastriate visual pathway and the risk management of post-operative VFD in epilepsy surgery.

Impact of PEEP during laparoscopic surgery on early postoperative ventilation distribution visualized by electrical impedance tomography.

BACKGROUND: General anesthesia, mechanical ventilation and pneumoperitoneum affect ventilation distribution at different extent. It should be clarified if an intraoperative positive end-expiratory pressure (PEEP) level of 10 cmH2O influences early postoperative ventilation. Electrical impedance tomography (EIT) was used to assess changes in regional ventilation. METHODS: Thirty-two patients (ASA physical status I/II) scheduled to undergo elective laparoscopic cholecystectomy were enrolled. The patients were randomly assigned to PEEP (10 cmH2O) or ZEEP group (0 cmH2O). EIT was performed before induction of anesthesia (T0) and after admission to the recovery room (T1-4). Ventral/dorsal and right/left lung impedance ratio (IR) and the center-of-ventilation index (COV) were calculated to investigate the differences in homogeneity of ventilation. RESULTS: Compared to preoperative data a significant increase in PaCO2 and reduction of pH values could be found in both groups. Significant decrease of postoperative tidal impedance change (∆Z) as well as a general postoperative ventral shift of the ventilation indicated by changes of IR and COV could be found in both groups. In ZEEP group IR and COV differed significantly from baseline (T0). In PEEP group there was just significant difference in COV at T2-T4 compared to T0. In the early postoperative period (T1) there was no difference in ventilation distribution in PEEP patients. CONCLUSION: Changes of postoperative ventilation can be imaged by EIT. Intraoperative PEEP ventilation has a positive effect on early postoperative ventilation distribution, even though not all PEEP patients benefit from mechanical PEEP ventilation the same way. Intraoperative PEEP results in a more homogeneous ventilation distribution by trend.

Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study.

BACKGROUND & AIMS: Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here. METHODS: QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05 mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale. RESULTS: PS reductions were associated with QoL improvements (ANCOVA, p = 0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100 cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL. CONCLUSIONS: Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo.

Development and validation of the disease-specific Short Bowel Syndrome-Quality of Life (SBS-QoL™) scale.

BACKGROUND & AIMS: Subjects with short bowel syndrome (SBS) have impaired quality of life (QoL). No disease-specific instrument has been available to measure treatment-induced changes in QoL over time. Therefore, the aim was to develop and validate an SBS-specific QoL scale. METHODS: Classical test theory and Food and Drug Administration (FDA) guidance were applied for development and validation of the SBS-QoL™. Procedures included item generation and raw scale construction. Factor analysis, construct validity and internal consistency were assessed in a non-interventional observation, test re-test reliability and responsiveness in a randomised clinical study. RESULTS: The SBS-QoL™ comprises 17 items including two subscales. Subjects assessed the scale as easy to handle and comprehensible. Good construct validity was shown by comparison with the Home Parenteral Nutrition-Quality Of Life questionnaire as an external scale, which yielded moderately high correlation (r ≥ 0.7). High internal consistency was demonstrated (Cronbach's alpha: 0.94). Also the test re-test reliability was high (r ≥ 0.95), indicating reliable reproducibility of results. The Responsiveness Index (1.84) indicated the ability of the scale to detect changes in QoL over time. CONCLUSIONS: The SBS-QoL™ is an easy to handle and comprehensible SBS-specific subject-reported QoL scale. It is valid, reliable and sensitive with excellent psychometric characteristics to measure treatment-induced changes in QoL over time in subjects with SBS.

Lack of agreement between pulmonary arterial thermodilution cardiac output and the pressure recording analytical method in postoperative cardiac surgery patients.

BACKGROUND: Pulse-contour analysis method (PCM) cardiac output (CO) monitors are increasingly used for CO monitoring during anaesthesia and in the critically ill. Very recently, several systems have been introduced that do not need calibration; among them the pressure recording analytical method (PRAM). Sparse data comparing the accuracy of the PRAM-CO with conventional thermodilution CO (ThD-CO) in cardiac surgery patients are available. METHODS: In this prospective comparison study, paired CO measurements with a pulmonary artery catheter and a PRAM monitoring set were obtained 20-30 min apart (t1, t2) in 23 extubated patients on the first postoperative day after cardiac surgery. Data were analysed by the Bland-Altman method. RESULTS: A total of 46 paired CO measurements (23 for each interval) were collected. The Bland-Altman analysis showed a mean difference (bias) of 0.0 litre min(-1) and limits of agreement (1.96 sd) of 4.53 to -4.54 litre min(-1) [upper 95% confidence interval (CI), 3.26-5.80; lower 95% CI, -5.8 to -3.27]. The percentage error (1.96 sd/mean of the reference method) was 87%. CONCLUSIONS: These results question the reliability of the PRAM technology for the determination of CO in postoperative cardiac surgery patients.

[Anti-inflammatory effects of pentoxifylline: importance in cardiac surgery]. / Antiinflammatorische Effekte von Pentoxifyllin : Bedeutung bei herzchirurgischen Eingriffen.

Initially introduced as a rheologic agent for use in intermittent claudication due to peripheral artery disease and in ischemic cerebrovascular disease, the methylxanthine derivative pentoxifylline (PTX) has been shown to possess several anti-inflammatory properties which make this drug an interesting immunomodulating adjunct for the management of patients undergoing cardiac surgery. As an unspecific phosphodiesterase inhibitor PTX ameliorates the inflammatory response following a septic stimulus and blunts organ dysfunction after ischemia-reperfusion injury. Apart from this several small clinical studies have shown that the use of PTX may blunt the inflammatory response induced by cardiac surgery using a cardiopulmonary bypass. Additionally it has been shown that the perioperative application of this drug may improve postoperative function of organs at risk, such as the kidneys and liver.

The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease.

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and NTproBNP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.

Rapid recurrent processing gates awareness in primary visual cortex.

Visual awareness has been proposed to depend on recurrent processing in early visual cortex areas including the primary visual cortex (V1). Here, we address this hypothesis with high spatiotemporal resolution magnetoencephalographic recordings in subjects performing a substitution masking paradigm. Neural activity reflecting awareness is assessed by directly comparing the neuromagnetic response elicited by effectively and ineffectively masked targets after the proportion of trials leading to masking was individually adjusted to match the proportion of trials without masking. This revealed a modulation of recurrent activity in the primary visual cortex rapidly after the onset of the feedforward sweep of processing in striate and extrastriate areas but significantly before the onset of attention-dependent recurrent modulations in V1. Our data provide direct support for the notion that (i) recurrent processing in V1 correlates with visual awareness and (ii) that attention and awareness involve distinct recurrent processing operations.

Goal-directed hemodynamic optimization in high-risk cardiac surgery patients: a tale from the past or a future obligation?

The present manuscript summarizes the available evidence on outcome-related hemodynamic variables and ''goal-directed hemodynamic optimization'' strategies in patients undergoing cardiac surgery.

Histopathology and serial, multimodal magnetic resonance imaging in a multiple sclerosis variant.

Defining tools in magnetic resonance imaging (MRI) representing specific pathological processes is needed to understand the complex relationship between inflammation, myelin breakdown, axonal injury and clinical symptoms in multiple sclerosis (MS) and its variants. Here, we describe a case of histologically-defined MS, in which the radiological appearance of the lesion and clinical course support the diagnosis of Balo's concentric sclerosis. Serial magnetization transfer, diffusion tensor imaging and 1H-magnetic resonance spectroscopy, from 14 days to 13 months after biopsy, allow the contextual interpretation of specific pathological changes. In our case, acute inflammation was sensitively traced by fractional anisotropy and increased lactate in spectroscopy. In contrast, magnetization transfer ratio and the apparent diffusion coefficient monitor the sequential loss of tissue in selected rings of the lesion. The delay from the peak of symptoms in a dramatic clinical course to the maximum tissue destruction indicated through MRI suggests that compromise of axonal function may be decisive for the acute clinical situation. This is the first report comparing 1H-magnetic resonance spectroscopy, magnetization transfer and diffusion tensor imaging with histopathology in a patient with Balo's concentric sclerosis.

Effects of intra-aortic balloon counterpulsation on parameters of tissue oxygenation.

BACKGROUND AND OBJECTIVE: To investigate the effects of intra-aortic balloon pump therapy on parameters of global and regional oxygenation in patients undergoing cardiac surgery. METHODS: As part of a large surveillance study in cardiac surgery patients (n=266) we retrospectively analyzed the course of 28 patients requiring intra-aortic balloon pump therapy. Patients were grouped according to the time point of pump insertion (during weaning from cardiopulmonary bypass: group early intra-aortic balloon pumping (n=17); after admission to the intensive care unit: group late intra-aortic balloon pumping (n=9). Haemodynamic and tonometric variables, arterial lactate, and use of catecholamines were measured hourly. MEASUREMENTS AND RESULTS: Cardiac index increased in both groups after intra-aortic balloon pump insertion (2.2+/-0.5 baseline; 3.4+/-0.8 L min-1 m-2 4 h later (group early intra-aortic balloon pumping); 2.8+/-0.5 baseline, 3.6+/-L min-1 m-2 4 h later (group later intra-aortic balloon pumping), each P<0.05), there were no differences between groups. Arterial lactate values increased in group later intra-aortic balloon pumping after pump insertion to a maximum 2 h later (8.4+/-6.1 mmol L-1 baseline; 12.7+/-7.4 mmol L-1, P<0.05), and decreased continuously afterwards. The difference of arterial and gastric CO2 showed a sharp decrease after pump insertion in group later intra-aortic balloon pumping (26.4+/-9.8 baseline; 7.0+/-11.1 mmHg, P<0.05). There were no differences between groups. Epinephrine doses were higher in group later intra-aortic balloon pumping (P<0.05). CONCLUSIONS: Intra-aortic balloon pump therapy improved global and regional splanchnic oxygenation in cardiac surgery patients with low-cardiac-output syndrome. Gastro-intestinal tonometry could provide additional information concerning tissue oxygenation. Patients with later intra-aortic balloon pump insertion needed more catecholamine therapy to achieve similar haemodynamic values.

Form-from-motion: MEG evidence for time course and processing sequence.

The neural mechanisms and role of attention in the processing of visual form defined by luminance or motion cues were studied using magnetoencephalography. Subjects viewed bilateral stimuli composed of moving random dots and were instructed to covertly attend to either left or right hemifield stimuli in order to detect designated target stimuli that required a response. To generate form-from-motion (FFMo) stimuli, a subset of the dots could begin to move coherently to create the appearance of a simple form (e.g., square). In other blocks, to generate form-from-luminance (FFLu) stimuli that served as a control, a gray stimulus was presented superimposed on the randomly moving dots. Neuromagnetic responses were observed to both the FFLu and FFMo stimuli and localized to multiple visual cortical stages of analysis. Early activity in low-level visual cortical areas (striate/early extrastriate) did not differ for FFLu versus FFMo stimuli, nor as a function of spatial attention. Longer latency responses elicited by the FFLu stimuli were localized to the ventral-lateral occipital cortex (LO) and the inferior temporal cortex (IT). The FFMo stimuli also generated activity in the LO and IT, but only after first eliciting activity in the lateral occipital cortical region corresponding to MT/V5, resulting in a 50-60 msec delay in activity. All of these late responses (MT/V5, LO, and IT) were significantly modulated by spatial attention, being greatly attenuated for ignored FFLu and FFMo stimuli. These findings argue that processing of form in IT that is defined by motion requires a serial processing of information, first in the motion analysis pathway from V1 to MT/V5 and thereafter via the form analysis stream in the ventral visual pathway to IT.

Neuromagnetic correlates of perceived contrast in primary visual cortex.

When a target grating is flashed into a larger, surrounding grating, its contrast is perceived to be lower when both gratings are oriented collinearly rather than orthogonally. This effect can be used to dissociate the perceived contrast from the physical contrast of a target grating. We recorded the transient electric potentials and magnetic fields evoked by flashed target gratings and compared them with psychophysical judgments of perceived contrast. Both early (100 ms) and late (150 ms) transients were reduced in amplitude when targets were flashed into a collinear rather than orthogonal surround, thus paralleling the reduction in perceived contrast. Although targets in orthogonal backgrounds required 40% lower physical contrast to match the perceived contrast of collinear targets, the amplitudes of electrophysiological transients of matching stimuli were almost identical. Thus the responses correlated better with perceived than with physical target contrast. This holds especially for the late transient response. Source localization indicated that the transients in question may originate in primary visual cortex. Our results therefore identify the activity of primary visual cortex as one possible neural correlate of perceived contrast.

Practicability of magnetoencephalography-guided neuronavigation.

Magnetoencephalography (MEG) is a noninvasive option for localizing electroneurophysiological activity on the human cortex. The purpose of this study was to evaluate the practicability and reliability of MEG imaging integrated into a neuronavigation system to identify the sensorimotor cortex intraoperatively in patients with brain tumors in or near the central motor strip. It was performed prior to surgery in 30 patients with space-occupying lesions in or around the central region to localize the primary somatosensory cortex. These functional brain maps were superimposed on MR images obtained prior to surgery and transferred in the operating room for intraoperative functional neuronavigation. During surgery, the phase reversal technique identified a generator which coincided with the somatosensory cortex as displayed by the MEG-based functional neuronavigation system. Following surgery, the motor deficit improved in seven patients, was unchanged in five, and showed a slight transient deterioration in five. One patient suffered a deterioration of motor function with incomplete recovery. The MEG-based functional neuronavigation was found to be practicable and useful in finding a safe approach to tumors in or adjacent to the central region. The accuracy of MEG was concluded to be reliable as verified by the phase reversal technique.

Defective mitochondrial oxidative phosphorylation in myopathies with tubular aggregates originating from sarcoplasmic reticulum.

Abnormalities of the sarcotubular system presenting as tubular aggregates (TAs) have been described in a variety of neuromuscular disorders. Here, we report on immunohistochemical and biochemical findings in 7 patients (2 familial and 5 sporadic cases) suffering from myopathies with TAs. In muscle biopsy specimens from 5 of the 7 patients, TAs were immunopositive for the ryanodine receptor (RYR 1) of the sarcoplasmic reticulum (SR), the SR Ca2+ pump (SERCA2-ATPase), and the intraluminal SR Ca2+ binding protein calsequestrin, indicating an SR origin of these aggregates. Furthermore, these 5 cases showed decreased respiratory chain enzyme activities (NADH:CoQ oxidoreductase. complex I and cytochrome c oxidase [COX], complex IV), while the remaining 2 patients exhibited normal values. Our findings indicate a functional link between mitochondrial dysfunction and the presence of TAs originating from the sarcoplasmic reticulum.