Quantification of propionaldehyde in breath of patients after lung transplantation.

Oxygen-derived free radicals (ROS) have been identified to contribute significantly to ischemia-reperfusion (I/R) injury by initiating chain reactions with polyunsaturated membrane lipids (lipid peroxidation, LPO) resulting in the generation of several aldehydes and ketones. Due to their volatile nature these LPO products can be measured noninvasively in breath. We hypothesized that one of these markers, namely propionaldehyde, will be increased in lung and heart-lung transplant patients where severe oxidative stress due to I/R injury with early graft dysfunction represents one of the major postoperative complications resulting in prolonged ventilation and increased in-hospital morbidity and mortality. Expiratory air measurements for acetone, isoprene, and propionaldehyde were performed in seven patients after lung (n = 5) or heart-lung (n = 2) transplantation, ventilated patients (n = 12), and healthy volunteers (n = 17) using online ion-molecule reaction mass spectrometry. Increased concentrations of acetone (transplanted: 3812 [2347-12498]; ventilated: 1255 [276-1959]; healthy: 631 [520-784] ppbv; P < .001) and propionaldehyde (transplanted: 270 [70-424]; ventilated: 82 [41.8-142]; healthy: 1.7 [0.1-11.8] ppbv; P < .001) were found in expiratory air of transplanted and ventilated patients. Propionaldehyde resulting from spontaneous fragmentation of peroxides due to free radical-induced LPO after I/R injury in patients after lung or heart-lung transplantation can be quantified in expired breath.

[Veno-arterial extracorporeal membrane oxygenation. Indications, limitations and practical implementation]. / Venoarterielle extrakorporale Membranoxygenierung. Indikationen, Limitationen und praktische Anwendung.

Due to the technical advances in pumps, oxygenators and cannulas, veno-arterial extracorporeal membrane oxygenation (va-ECMO) or extracorporeal life support (ECLS) has been widely used in emergency medicine and intensive care medicine for several years. An accepted indication is peri-interventional cardiac failure in cardiac surgery (postcardiotomy low cardiac output syndrome). Furthermore, especially the use of va-ECMO for other indications in critical care medicine, such as in patients with severe sepsis with septic cardiomyopathy or in cardiopulmonary resuscitation has tremendously increased. The basic indications for va-ECMO are therapy refractory cardiac or cardiopulmonary failure. The fundamental purpose of va-ECMO is bridging the function of the lungs and/or the heart. Consequently, this support system does not represent a causal therapy by itself; however, it provides enough time for the affected organ to recover (bridge to recovery) or for the decision for a long-lasting organ substitution by a ventricular assist device or by transplantation (bridge to decision). Although the outcome for bridged patients seems to be favorable, it should not be forgotten that the support system represents an invasive procedure with potentially far-reaching complications. Therefore, the initiation of these systems needs a professional and experienced (interdisciplinary) team, sufficient resources and an individual approach balancing the risks and benefits. This review gives an overview of the indications, complications and contraindications for va-ECMO. It discusses its advantages in organ transplantation and transport of critically ill patients. The reader will learn the differences between peripheral and central cannulation and how to monitor and manage va-ECMO.

[Quality of results of therapy of acute respiratory failure : changes over a period of two decades]. / Ergebnisqualität der Therapie des akuten Lungenversagens : Veränderungen über einen Zeitraum von 2 Jahrzehnten.

Progress in intensive care (ICU) treatment of acute respiratory distress syndrome (ARDS) over the last 20 years includes the introduction of extracorporeal membrane oxygenation (ECMO) for CO2 removal and the widespread use of evidence-based lung-protective ventilatory strategies. Little is known, however, about whether these changes have resulted in improvements in short-term and long-term outcome of acute respiratory distress syndrome (ARDS) within the two decades after introduction. In a retrospective study 167 long-term survivors of severe ARDS who were transferred to the clinic for anesthesiology of the University of Munich, Campus Großhadern by means of specialized intensive care unit (ICU) transport teams and treated over a period of 20 years (1985-2005) were evaluated to investigate whether significant improvements in outcome as a consequence of the above mentioned progress in ARDS therapy have occurred. The ARDS patient cohort studied was characterized with regard to demographic variables, initial acute physiology and chronic health evaluation (APACHE) II score, duration of ICU treatment, the duration of mechanical ventilation and mortality. Data on long-term outcome were collected in a subcohort (n = 125) of patients who responded to mailed questionnaires and included health-related quality of life (HRQL, SF-36 questionnaire), symptoms of post-traumatic stress disorder (PTSD), traumatic memories from ICU treatment (PTSS-10 instrument) and current state of employment. During the observation period no significant changes regarding patient age (39 ± 16 years, mean ± SD), disease severity on admission to the ICU (APACHE II scores 22 ± 5), duration of ICU treatment (47 ± 39 days) or duration of mechanical ventilation (39 ± 38 days) were found. Overall ICU mortality during the two decades was 37.3 % (range 25.0 %-38.1 %) between 1995 and 2001 and a non-significant increase in values between 36.8 % and 58.3 % during the time interval from 2002 und 2005. The paO2/FIO2-ratio on ICU admittance improved significantly between 1990 and 2000 (69 ± 5 between 1990 and 1994 versus 101 ± 12 between 1995 and 2000, p < 0.01) and remained nearly unchanged thereafter. Long-term outcome was evaluated on average 5.0 ± 3.1 years after discharge from the ICU. During the time period between 1985 and 1994 survivors of ARDS showed significant impairments in all 8 categories of the SF-36 HRQL instrument when compared to an age and sex-matched normal population with maximal differences regarding physical function (z = -1.01), general health perception (z = -1.17) and mental health (z = -1.3). Patients who were treated from 1995 to 2005 were still impaired in 7 out of 8 categories of HRQL but reported significantly better mental health (49.6 ± 16.5 vs. 68.6 ± 17.8, p < 0,01) and better physical function than individuals from the previous decade (49.6 ± 16.5 vs. 73.4 ± 27.5, p = 0,03). The difference of mental health was no longer significant when compared to a healthy age and sex matched control group (p = 0.14) but the difference in physical function still was (z = -0.48, p < 0.01). The incidence of severe post-traumatic stress defined as a PTSS-10 score ≥ 35 was 20.4 % and remained unchanged throughout the 2 decades of observation. The PTSS-10 scores correlated with the number of traumatic memories present (r = 0.43, p < 0.01, n = 125). More than 50 % of long-term survivors were able to return to full time work with no significant changes during the 2 decades of observation. The introduction of new modalities of ARDS treatment were associated with higher paO2/FIO2-ratios on ICU admittance but had no effect on short-term outcomes including duration of ICU therapy, mechanical ventilation or mortality. The ARDS patients are still at risk for post-traumatic stress and persistent impairments in HRQL. Apart from some improvements in HRQL, the outcome of ARDS therapy remained largely unchanged during two decades.

Volatile compound profiling for the identification of Gram-negative bacteria by ion-molecule reaction-mass spectrometry.

AIMS: Fast and reliable methods for the early detection and identification of micro-organism are of high interest. In addition to established methods, direct mass spectrometry-based analysis of volatile compounds (VCs) emitted by micro-organisms has recently been shown to allow species differentiation. Thus, a large number of pathogenic Gram-negative bacteria, which comprised Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa, Proteus vulgaris and Serratia marcescens, were subjected to headspace VC composition analysis using direct mass spectrometry in a low sample volume that allows for automation. METHODS AND RESULTS: Ion-molecule reaction-mass spectrometry (IMR-MS) was applied to headspace analysis of the above bacterial samples incubated at 37°C starting with 10(2) CFU ml(-1) . Measurements of sample VC composition were performed at 4, 8 and 24 h. Microbial growth was detected in all samples after 8 h. After 24 h, species-specific mass spectra were obtained allowing differentiation between bacterial species. CONCLUSIONS: IMR-MS provided rapid growth detection and identification of micro-organisms using a cumulative end-point model with a short analysis time of 3 min per sample. SIGNIFICANCE AND IMPACT OF THE STUDY: Following further validation, the presented method of bacterial sample headspace VC analysis has the potential to be used for bacteria differentiation.

Volatile organic compound analysis by ion molecule reaction mass spectrometry for Gram-positive bacteria differentiation.

Approximately 50 % of all clinically proven infections in critically ill patients are caused by Gram-positive bacteria. The timely and appropriate treatment of these infections is vital in order to avoid negative outcomes. Hence, fast and reliable methods are needed for the early detection and identification of microorganisms. Recently, direct mass spectrometry-based analysis of volatile organic compounds emitted by microorganisms has been employed to study Gram-negative bacteria. Here, we report a feasibility study of ion molecule reaction mass spectrometry (IMR-MS) for in vitro growth detection and species differentiation of selected Gram-positive bacteria that are frequently isolated in blood culture samples, namely, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Staphylococcus epidermidis. Ion molecule reaction mass spectrometry was used to analyze the headspace above cultures containing Gram-positive bacteria incubated at 37 °C starting with 10(2) colony-forming units (CFU)/ml. Measurements to determine the presence of volatile organic compounds were performed 4, 8, and 24 h after incubation, respectively. The detection of microbial growth was accomplished already after 8 h in cultures containing E. faecalis. After 24 h of incubation, characteristic mass spectra were obtained for all species. Processing these mass spectra by hierarchic clustering and principal component analysis (PCA) enabled us to differentiate between bacterial species. IMR-MS in conjunction with a cumulative end-point model provides the means for rapid growth detection and differentiation of Gram-positive bacteria on the species level, typically within an analysis time of less than 3 min per sample.

Long-term isoflurane therapy for refractory bronchospasm associated with herpes simplex pneumonia in a heart transplant patient.

A 47-year-old man with a history of heart transplant was admitted after severe traumatic brain injury and seizures. During mechanical ventilation, the patient developed bronchospasm that severely compromised respiratory function that led to cardiac arrest. After resuscitation, application of isoflurane through the Anaesthetic Conserving Device (AnaConDa) in the ICU successfully treated bronchospasm, provided adequate sedation, and enabled appropriate ventilation and diagnostic bronchoscopy. A subsequent bronchoalveolar lavage revealed a high amount of Herpes simplex DNA. Herpes simplex pneumonia was diagnosed and treated with acyclovir. Isoflurane treatment was applied for twelve days total without side effects on renal and cerebral function. The patient recovered quickly after the termination of sedation. At discharge, he was fully awake without focal neurological deficiency and his long-term outcome was excellent. This case demonstrates that isoflurane is a treatment option in life-threatening cases of bronchospasm and a safe option for long-term sedation.

Molecular breath-gas analysis by online mass spectrometry in mechanically ventilated patients: a new software-based method of CO(2)-controlled alveolar gas monitoring.

Analysis of volatile organic compounds (VOCs) in exhaled breath offers diagnostic potential in research and clinical medicine. Mass spectrometry of expiratory air allows VOC measurements in a concentration range from parts per trillion to parts per million. For the reduction of dilution-related measurement errors due to dead space admixture, the precise identification of the end-expiratory phase of expiration is essential. We used a combination of two integrated MS systems consisting of a conventional MS capable of fast CO(2) tracing controlling a second, highly sensitive MS for the measurement of VOCs based on ion-molecule-reaction-MS (IMR-MS). This study intended to test the applicability of a software-based method of CO(2)-controlled alveolar breath-gas sampling in 12 ventilated patients using acetaldehyde, acetone, ethanol and isoprene as target VOCs (IMR-MS compound integration time 500 ms, cycle time 2 ms, measurement time 120 min). CO(2)-controlled versus mixed inspiratory/expiratory results are as follows: acetaldehyde 71* (61-133) versus 63 (47-87); acetone 544* (208-1174) versus 504 (152-950); ethanol 133 (99-166) versus 123 (108-185); isoprene 118* (69-253) versus 58 (44-112) (values in ppbv as medians with 25-75%; *p < 0.05 versus mixed inspiratory/expiratory values). The applied software-based CO(2)-controlled sampling method of expiratory air resulted in significant higher concentrations of acetaldehyde, acetone and isoprene.

Early effect of low-dose endotoxin on rat cecal mucosa ex vivo.

It has been suggested that endotoxin triggers translocation of intestinal bacteria in vivo, either by directly damaging intestinal mucosa or by inducing a systemic inflammatory reaction that leads to mucosal disruption. To address this issue, we examined the immediate effect of extraluminal endotoxin on structure and function of isolated rat cecal mucosa without other inflammatory cells in vitro. The cecal mucosa of 12 male Wistar rats was mounted in modified Ussing chambers filled with Dulbecco's modified Eagle's medium and the ampicillin-resistant Escherichia coli HB101:K12 incubated on the mucosal side. Endotoxin was added to the submucosal side at concentrations of 1 and 10 EU/ml, respectively. Under gassing with carbogene at 37 degreesC, the potential difference across the mucosa was measured continuously. Samples of the mucosal and submucosal solutions were removed at 60, 120, and 180 min and plated out on McConkey ampicillin-agar. After 180 min, the mucosal specimens were retrieved and examined by light and scanning electron microscopy. No significant change in potential difference was observed in control or endotoxin-incubated mucosa within the observation period. Neither light nor scanning electron microscopy showed a significant change in the structure of the epithelium, mucosa, or submucosa. No significant translocation of the E. coli across the mucosa was seen. We concluded that endotoxin alone does not induce immediate structural and functional damage to rat cecal mucosa in vitro. Therefore, it seems unlikely that a short endotoxemia alone directly triggers bacterial translocation by disrupting intestinal mucosa, but rather, entotoxin induces a local and systemic inflammatory reaction that leads to mucosal disruption.