Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial.

BACKGROUND: Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes. METHODS: In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration. RESULTS: In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation. CONCLUSION: During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation. REGISTRATION OF CLINICAL TRIAL: DRKS-ID DRKS00014788 (www.drks.de).

[Caudal Anesthesia: Overview and Practical Recommendations]. / Kaudalanästhesie: Übersicht und praktische Handlungsempfehlungen.

Caudal anesthesia is one of the most commonly performed forms of regional anesthesia in childhood, which is relatively easy to learn and very effective. Indications for sacral block are all interventions below the costal arch. The puncture can be performed on premature babies and children up to 50 kg body weight. The use of ultrasound increases the success rate and verifies the epidural injection. Bupivacaine and ropivacaine can be combined with adjuvants such as clonidine, morphine or ketamine, which lead to a prolonged effect. In selected patient groups, the operation can also be performed under caudal anesthesia with sedation in order to maintain spontaneous breathing and avoid respiratory complications. This review article gives an overview of caudal anesthesia and offers practical instructions for blocks during general anesthesia and sedation.

Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury.

BACKGROUND: Mechanical ventilation injures lungs, but there are currently no reliable methods for detecting early injury. We therefore evaluated whether exhaled pentanal, a lipid peroxidation product, might be a useful breath biomarker for stretch-induced lung injury in rats. METHODS: A total of 150 male Sprague-Dawley rats were investigated in 2 substudies. The first randomly assigned 75 rats to 7 hours of mechanical ventilation at tidal volumes of 6, 8, 12, 16, and 20 mL·kg-1. The second included 75 rats. A reference group was ventilated at a tidal volume of 6 mL·kg-1 for 10 hours 4 interventional groups were ventilated at a tidal volume of 6 mL·kg-1 for 1 hour, and then for 0.5, 1, 2, or 3 hours at a tidal volume of 16 mL.kg-1 before returning to a tidal volume of 6 mL·kg-1 for additional 6 hours. Exhaled pentanal was monitored by multicapillary column-ion mobility spectrometry. The first substudy included cytokine and leukocyte measurements in blood and bronchoalveolar fluid, histological assessment of the proportion of alveolar space, and measurements of myeloperoxidase activity in lung tissue. The second substudy included measurements of pentanal in arterial blood plasma, cytokine and leukocyte concentrations in bronchoalveolar fluid, and cleaved caspase 3 in lung tissue. RESULTS: Exhaled pentanal concentrations increased by only 0.5 ppb·h-1 (95% confidence interval [CI], 0.3-0.6) when rats were ventilated at 6 mL·kg-1. In contrast, exhaled pentanal concentrations increased substantially and roughly linearly at higher tidal volumes, up to 3.1 ppb·h-1 (95% CI, 2.3-3.8) at tidal volumes of 20 mL·kg-1. Exhaled pentanal increased at average rates between 1.0 ppb·h-1 (95% CI, 0.3-1.7) and 2.5 ppb·h-1 (95% CI, 1.4-3.6) after the onset of 16 mL·kg-1 tidal volumes and decreased rapidly by a median of 2 ppb (interquartile range [IQR], 0.9-3.2), corresponding to a 38% (IQR, 31-43) reduction when tidal volume returned to 6 mL·kg-1. Tidal volume, inspiratory pressure, and mechanical power were positively associated with pentanal exhalation. Exhaled and plasma pentanal were uncorrelated. Alveolar space decreased and inflammatory markers in bronchoalveolar lavage fluid increased in animals ventilated at high tidal volumes. Short, intermittent ventilation at high tidal volumes for up to 3 hours increased neither inflammatory markers in bronchoalveolar fluid nor the proportion of cleaved caspase 3 in lung tissue. CONCLUSIONS: Exhaled pentanal is a potential biomarker for early detection of ventilator-induced lung injury in rats.

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients.

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column-ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power-a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury.

Preparing for the SARS-CoV-2 pandemic: creation and implementation of new recommendations.

During the SARS-CoV-2 pandemic in 2020, departments of anesthesiology worldwide have encountered new and unique challenges. In this short communication, we present and assess our recommendations for orotracheal intubation, a frequent high-risk procedure. We will point out that interdisciplinary cooperation with "non-patient care" departments like the Institute for Medical Microbiology and Hygiene tremendously helped us in creating this and other new, clear standards for anesthesiological procedures. Moreover, to reliably implement our newly created measures, we distributed incisive posters and organized comprehensive training sessions. Eventually, we summarize and analyze the occurring problems of our suggestions for intubation during their realization.

[Diabetes mellitus in Anaesthesia - Optimal Blood Sugar Control in the Perioperative Phase]. / Diabetes mellitus in der Anästhesie ­ optimale perioperative Blutzuckerkontrolle.

Uncontrolled high blood sugar can be dangerous for diabetics throughout the perioperative period - in particular, when blood glucose levels exceed a threshold of 250 mg/dl or HbA1c levels are higher than 8.5 - 9%. In such cases, all elective surgery should be withheld to minimize the risk of severe complications. Due to their cardiovascular comorbidities, diabetics are commonly overrepresented in hospitals, tend to require inpatient care for an extended period of time, and suffer from higher mortality rates. In order to reduce negative outcomes, blood glucose levels should be targeted to 140 - 180 mg/dl on intensive care units or during surgery. Current literature suggests that non-critically ill diabetics should be treated with rapid-acting insulin analogues subcutaneously in operating theatres, whereas critically ill patients should receive continuous intravenous insulin infusions using a standardized protocol. In summary, this review can give a hand in dealing with diabetics during the perioperative period and offers guidance in controlling blood sugar levels with the help of oral antidiabetic drugs and insulin.

Residual volatile anesthetics after workstation preparation and activated charcoal filtration.

BACKGROUND: Volatile anesthetics potentially trigger malignant hyperthermia crises in susceptible patients. We therefore aimed to identify preparation procedures for the Draeger Primus that minimize residual concentrations of desflurane and sevoflurane with and without activated charcoal filtration. METHODS: A Draeger Primus test workstation was primed with 7% desflurane or 2.5% sevoflurane for 2 hours. Residual anesthetic concentrations were evaluated with five preparation procedures, three fresh gas flow rates, and three distinct applications of activated charcoal filters. Finally, non-exchangeable and autoclaved parts of the workstation were tested for residual emission of volatile anesthetics. Concentrations were measured by multicapillary column-ion mobility spectrometry with limits of detection/quantification being <1 part per billion (ppb) for desflurane and <2.5 ppb for sevoflurane. RESULTS: The best preparation procedure included a flushing period of 10 minutes between removal and replacement of all parts of the ventilator circuit which immediately produced residual concentrations <5 ppm. A fresh gas flow of 10 L/minute reduced residual concentration as effectively as 18 L/minute, whereas flows of 1 or 5 L/minute slowed washout. Use of activated charcoal filters immediately reduced and maintained residual concentrations <5 ppm for up to 24 hours irrespective of previous workstation preparation. The fresh gas hose, circle system, and ventilator diaphragm emitted traces of volatile anesthetics. CONCLUSION: In elective cases, presumably safe concentrations can be obtained by a 10-minute flush at ≥10 L/minute between removal and replacement all components of the airway circuit. For emergencies, we recommend using an activated charcoal filter.

Volatile organic compounds in head and neck squamous cell carcinoma-An in vitro pilot study.

Owing to the lack of specific symptoms, diagnosis of head and neck squamous cell carcinoma (HNSCC) may be delayed. We evaluated volatile organic compounds in tumor samples from patients suffering from HNSCC and tested the hypothesis that there is a characteristic altered composition in the headspace of HNSCC compared with control samples from the same patient with normal squamous epithelium. These results provide the basis for future noninvasive breath analysis in HNSCC. Headspace air of suspected tumor and contralateral control samples in 20 patients were analyzed using ion-mobility spectrometry. Squamous cell carcinoma was diagnosed in 16 patients. In total, we observed 93 different signals in headspace measurements. Squamous cell carcinomas revealed significantly higher levels of volatile cyclohexanol (0.54 ppbv , 25th to 75th percentiles 0.35-0.86) compared with healthy squamous epithelium (0.24 ppbv , 25th to 75th percentiles 0.12-0.3; p < 0.001). In conclusion, head and neck squamous cell carcinoma emitted significantly higher levels of volatile cyclohexanol in headspace compared with normal squamous epithelium. These findings form the basis for future breath analysis for diagnosis, therapy control and the follow-up of HNSSC to improve therapy and aftercare.

Volatile Organic Compounds in Patients With Acute Kidney Injury and Changes During Dialysis.

OBJECTIVES: To characterize volatile organic compounds in breath exhaled by ventilated care patients with acute kidney injury and changes over time during dialysis. DESIGN: Prospective observational feasibility study. SETTING: Critically ill patients on an ICU in a University Hospital, Germany. PATIENTS: Twenty sedated, intubated, and mechanically ventilated patients with acute kidney injury and indication for dialysis. INTERVENTIONS: Patients exhalome was evaluated from at least 30 minutes before to 7 hours after beginning of continuous venovenous hemodialysis. MEASUREMENTS AND MAIN RESULTS: Expired air samples were aspirated from the breathing circuit at 20-minute intervals and analyzed using multicapillary column ion-mobility spectrometry. Volatile organic compound intensities were compared with a ventilated control group with normal renal function. A total of 60 different signals were detected by multicapillary column ion-mobility spectrometry, of which 44 could be identified. Thirty-four volatiles decreased during hemodialysis, whereas 26 remained unaffected. Forty-five signals showed significant higher intensities in patients with acute kidney injury compared with control patients with normal renal function. Among these, 30 decreased significantly during hemodialysis. Volatile cyclohexanol (23 mV; 2575th, 19-38), 3-hydroxy-2-butanone (16 mV, 9-26), 3-methylbutanal (20 mV; 14-26), and dimer of isoprene (26 mV; 18-32) showed significant higher intensities in acute kidney impairment compared with control group (12 mV; 10-16 and 8 mV; 7-14 and not detectable and 4 mV; 0-6; p < 0.05) and a significant decline after 7 hours of continuous venovenous hemodialysis (16 mV; 13-21 and 7 mV; 6-13 and 9 mV; 8-13 and 14 mV; 10-19). CONCLUSIONS: Exhaled concentrations of 45 volatile organic compounds were greater in critically ill patients with acute kidney injury than in patients with normal renal function. Concentrations of two-thirds progressively decreased during dialysis. Exhalome analysis may help quantify the severity of acute kidney injury and to gauge the efficacy of dialysis.

Image quality to estimate ventricular ejection fraction by last year medical students improves after short courses of training.

BACKGROUND: Transthoracic echocardiography is the primary imaging modality for diagnosing cardiac conditions but medical education in this field is limited. We tested the hypothesis that a structured theoretical and supervised practical course of training in focused echocardiography in last year medical students results in a more accurate assessment and more precise calculation of left ventricular ejection fraction after ten patient examinations. METHODS: After a theoretical introduction course 25 last year medical students performed ten transthoracic echocardiographic examination blocks in postsurgical patients. Left ventricular function was evaluated both with an eye-balling method and with the calculated ejection fraction using diameter and area of left ventricles. Each examination block was controlled by a certified and blinded tutor. Bias and precision of measurements were assessed with Bland and Altman method. RESULTS: Using the eye-balling method students agreed with the tutor's findings both at the beginning (88%) but more at the end of the course (95.7%). The variation between student and tutor for calculation of area, diameter and ejection fraction, respectively, was significantly lower in examination block 10 than in examination block 1 (each p < 0.001). Students underestimated both the length and the area of the left ventricle at the outset, as complete imaging of the left heart in the ultrasound sector was initially unsuccessful. CONCLUSIONS: A structured theoretical and practical transthoracic echocardiography course of training for last year medical students provides a clear and measurable learning experience in assessing and measuring left ventricular function. At least 14 examination blocks are necessary to achieve 90% agreement of correct determination of the ejection fraction.

[Upper Age Limit in Outpatient Anesthesia: Opportunities and Risks]. / Obere Altersgrenze bei ambulanter Anästhesie: Möglichkeiten und Risiken.

Ambulatory surgery in elderly patients continues to increase - avoiding hospitalization and thus postoperative cognitive dysfunction in older patients being its major objectives. An upper age limit in outpatient anesthesia does not exist to date. However, functional rather than chronological age is crucial in patient selection. In consensus discussion, baseline functional status should be evaluated regularly - defined as everyday behaviors necessary to maintain daily life and encompassing areas of physical, cognitive, and social functioning. Moreover, frailty in elderly patients can be quantified objectively and is associated with increased perioperative morbidity in ambulatory general surgery. The decision for or against outpatient anesthesia therefore remains a case-by-case decision which should be discussed within a team.

Volatile organic compounds in ventilated critical care patients: a systematic evaluation of cofactors.

BACKGROUND: Expired gas (exhalome) analysis of ventilated critical ill patients can be used for drug monitoring and biomarker diagnostics. However, it remains unclear to what extent volatile organic compounds are present in gases from intensive care ventilators, gas cylinders, central hospital gas supplies, and ambient air. We therefore systematically evaluated background volatiles in inspired gas and their influence on the exhalome. METHODS: We used multi-capillary column ion-mobility spectrometry (MCC-IMS) breath analysis in five mechanically ventilated critical care patients, each over a period of 12 h. We also evaluated volatile organic compounds in inspired gas provided by intensive care ventilators, in compressed air and oxygen from the central gas supply and cylinders, and in the ambient air of an intensive care unit. Volatiles detectable in both inspired and exhaled gas with patient-to-inspired gas ratios < 5 were defined as contaminating compounds. RESULTS: A total of 76 unique MCC-IMS signals were detected, with 39 being identified volatile compounds: 73 signals were from the exhalome, 12 were identified in inspired gas from critical care ventilators, and 34 were from ambient air. Five volatile compounds were identified from the central gas supply, four from compressed air, and 17 from compressed oxygen. We observed seven contaminating volatiles with patient-to-inspired gas ratios < 5, thus representing exogenous signals of sufficient magnitude that might potentially be mistaken for exhaled biomarkers. CONCLUSIONS: Volatile organic compounds can be present in gas from central hospital supplies, compressed gas tanks, and ventilators. Accurate assessment of the exhalome in critical care patients thus requires frequent profiling of inspired gases and appropriate normalisation of the expired signals.

Exhalation pattern changes during fasting and low dose glucose treatment in rats.

The analysis of exhaled metabolites has become a promising field of research in recent decades. Several volatile organic compounds reflecting metabolic disturbance and nutrition status have even been reported. These are particularly important for long-term measurements, as needed in medical research for detection of disease progression and therapeutic efficacy. In this context, it has become urgent to investigate the effect of fasting and glucose treatment for breath analysis. In the present study, we used a model of ventilated rats that fasted for 12 h prior to the experiment. Ten rats per group were randomly assigned for continuous intravenous infusion without glucose or an infusion including 25 mg glucose per 100 g per hour during an observation period of 12 h. Exhaled gas was analysed using multicapillary column ion-mobility spectrometry. Analytes were identified by the BS-MCC/IMS database (version 1209; B & S Analytik, Dortmund, Germany). Glucose infusion led to a significant increase in blood glucose levels (p < 0.05 at 4 h and thereafter) and cardiac output (p < 0.05 at 4 h and thereafter). During the observation period, 39 peaks were found collectively. There were significant differences between groups in the concentration of ten volatile organic compounds: p < 0.001 at 4 h and thereafter for isoprene, cyclohexanone, acetone, p-cymol, 2-hexanone, phenylacetylene, and one unknown compound, and p < 0.001 at 8 h and thereafter for 1-pentanol, 1-propanol, and 2-heptanol. Our results indicate that for long-term measurement, fasting and the withholding of glucose could contribute to changes of volatile metabolites in exhaled air.

Population pharmacokinetic modeling of multiple-dose intravenous fosfomycin in critically ill patients during continuous venovenous hemodialysis.

The aim of this study was to investigate the pharmacokinetics of multiple-dose intravenous (i.v.) fosfomycin in critically ill patients during continuous venovenous hemodialysis (CVVHD). Non-compartmental analysis and population pharmacokinetic modeling were used to simulate different dosing regimens. We evaluated 15 critically ill patients with renal insufficiency and CVVHD undergoing anti-infective treatment with fosfomycin in our ICU. Five grams of fosfomycin were administered for 120 min every 6 h. Plasma concentrations were determined with and without CVVHD. Pharmacokinetic analysis and simulations were performed using non-linear mixed effects modelling (NONMEM). A two-compartment model with renal and dialysis clearance was most accurate in describing the pharmacokinetics of i.v. fosfomycin during CVVHD. Population parameter estimates were 18.20 L and 20.80 L for the central and peripheral compartment volumes, and 0.26 L/h and 5.08 L/h for renal and intercompartmental clearance, respectively. Urinary creatinine clearance (CLCR) represented a considerable component of renal clearance. Central compartment volume increased over time after the first dose. For patients with CLCR > 50 (90) mL/min and CVVHD, dosage should be increased to ≥ 15 (16) grams of i.v. fosfomycin across three (four) daily doses. Individual CLCR must be considered when dosing i.v. fosfomycin in critically ill patients during CVVHD.

Intravenous propofol, ketamine (ketofol) and rocuronium after sevoflurane induction provides long lasting anesthesia in ventilated rats.

Rats are commonly used animals for laboratory experiments and many experiments require general anesthesia. However, the lack of published and reproducible intravenous anesthesia protocols for rats results in unnecessary animal use to establish new anesthesia techniques across institutions. We therefore developed an anesthesia protocol with propofol, ketamine, and rocuronium for mechanically ventilated rats, and evaluated vital parameters and plasma concentrations. 15 male Sprague-Dawley rats underwent inhalation induction with sevoflurane and tracheal, venous and arterial cannulation. After established venous access, sevoflurane was substituted by propofol and ketamine (ketofol). Rocuronium was added under mechanical ventilation for 7 h. Drug dosages were stepwise reduced to prevent accumulation. All animals survived the observation period and showed adequate depth of anesthesia. Mean arterial pressure and heart rate remained within normal ranges. Median propofol plasma concentrations remained stable: 1, 4, 7 h: 2.0 (interquartile range (IQR): 1.8-2.2), 2.1 (1.8-2.2), 1.8 (1.6-2.1) µg/ml, whereas median ketamine concentrations slightly differed after 7 h compared to 1 h: 1, 4, 7 h: 3.7 (IQR: 3.5-4.5), 3.8 (3.3-4.1), 3.8 (3.0-4.1) µg/ml. Median rocuronium plasma concentrations were lower after 4 and 7 h compared to 1 h: 1, 4, 7 h: 3.9 (IQR: 3.5-4.9), 3.2 (2.7-3.3), 3.0 (2.4-3.4) µg/ml. Our anesthesia protocol provides stable and reliable anesthesia in mechanically ventilated rats for several hours.

Quantification of Volatile Acetone Oligomers Using Ion-Mobility Spectrometry.

BACKGROUND: Volatile acetone is a potential biomarker that is elevated in various disease states. Measuring acetone in exhaled breath is complicated by the fact that the molecule might be present as both monomers and dimers, but in inconsistent ratios. Ignoring the molecular form leads to incorrect measured concentrations. Our first goal was to evaluate the monomer-dimer ratio in ambient air, critically ill patients, and rats. Our second goal was to confirm the accuracy of the combined (monomer and dimer) analysis by comparison to a reference calibration system. METHODS: Volatile acetone intensities from exhaled air of ten intubated, critically ill patients, and ten ventilated Sprague-Dawley rats were recorded using ion-mobility spectrometry. Acetone concentrations in ambient air in an intensive care unit and in a laboratory were determined over 24 hours. The calibration reference was pure acetone vaporized by a gas generator at concentrations from 5 to 45 ppbv (parts per billion by volume). RESULTS: Acetone concentrations in ambient laboratory air were only slightly greater (5.6 ppbv; 95% CI 5.1-6.2) than in ambient air in an intensive care unit (5.1 ppbv; 95% CI 4.4-5.5; p < 0.001). Exhaled acetone concentrations were only slightly greater in rats (10.3 ppbv; 95% CI 9.7-10.9) than in critically ill patients (9.5 ppbv; 95% CI 7.9-11.1; p < 0.001). Vaporization yielded acetone monomers (1.3-5.3 mV) and dimers (1.4-621 mV). Acetone concentrations (ppbv) and corresponding acetone monomer and dimer intensities (mV) revealed a high coefficient of determination (R 2 = 0.96). The calibration curve for acetone concentration (ppbv) and total acetone (monomers added to twice the dimers; mV) was described by the exponential growth 3-parameter model, with an R 2 = 0.98. CONCLUSION: The ratio of acetone monomer and dimer is inconsistent and varies in ambient air from place-to-place and across individual humans and rats. Monomers and dimers must therefore be considered when quantifying acetone. Combining the two accurately assesses total volatile acetone.

Quantitative Determination of Fosfomycin in 10 µL of Plasma and Dialysate by Hydrophilic Interaction Liquid Chromatography Electrospray Ionization Mass Spectrometry.

Fosfomycin is an antibiotic with a broad spectrum of activity against many multidrug-resistant bacterial strains. It is mainly excreted unchanged by the kidneys, and its half-life therefore depends on kidney function which varies considerably among individuals, and within individuals over time. Proper fosfomycin dosing thus depends on assaying blood concentration of the drug. We developed and validated a simple, sensitive and specific chromatography assay, which was coupled to electrospray ionization mass spectrometry for determination of fosfomycin. Separation of fosfomycin was based on the method of the hydrophilic interaction liquid chromatography; specifically, plasma and dialysate samples were acidified and the protein precipitated with acetonitrile. The calibration curves showed excellent coefficients of determination (R2 > 0.999) over the relevant concentration range of 25-700 µg/mL. Intraday precision was 1.1-1.2% and accuracy was -5.9% to 0.9% for quality control samples. Interday precision was 2.9-3.4% and accuracy was -3.7% to 5.5%. Extraction recovery was ≥87% and matrix effects ranged from 2.2% to 4.3%. After laboratory validation, the method was successfully applied to clinical samples.

Changes in volatile organic compounds provoked by lipopolysaccharide- or alpha toxin-induced inflammation in ventilated rats.

Inflammation may alter volatile organic compounds (VOCs) in exhaled breath. We therefore used ion mobility spectrometry (IMS) to evaluate exhaled breath components in two non-infectious inflammatory models. Fifty male Sprague Dawley rats were anesthetized and ventilated for 24 h. Five treatments were randomly assigned: (1) lipopolysaccharide low dose [5 mg/kg]; (2) lipopolysaccharide high dose [10 mg/kg]; (3) alpha toxin low dose [40 µg/kg]; (4) alpha toxin high dose [80 µg/kg]; and, (5) NaCl 0.9% as control group. Gas was sampled from the expiratory line of the ventilator every 20 min and analyzed with IMS combined with a multi-capillary column. VOCs were identified by comparison with an established database. Survival analysis was performed by log-rank test, other analyses by one-way or paired ANOVA-tests and post-hoc analysis according to Holm-Sidak. Rats given NaCl and low-dose alpha toxin survived 24 h. The median survival time in alpha toxin high-dose group was 23 (95%-confidence interval (CI): 21, 24) h. In contrast, the median survival time in rats given high-dose lipopolysaccharide was 12 (95% CI: 9, 14) and only 13 (95% CI: 10, 16) h in those given high-dose lipopolysaccharide. 73 different VOCs were detected, of which 35 were observed only in the rats, 38 could be found both in the blank measurements of ventilator air and in the exhaled air of the rats. Forty-nine of the VOCs were identifiable from a registry of compounds. Exhaled volatile compounds were comparable in each group before injection of lipopolysaccharide and alpha toxin. In the LPS groups, 1-pentanol increased and 2-propanol decreased. After alpha toxin treatment, 1-butanol and 1-pentanol increased whereas butanal and isopropylamine decreased. Induction of a non-infectious systemic inflammation (niSI) by lipopolysaccharide and alpha toxin changes VOCs in exhaled breath. Exhalome analysis may help identify niSI.