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.

Adverse effects of delta-9-tetrahydrocannabinol on sickle red blood cells.

THC triggers a pronounced entry of Ca2+ , which may be deleterious, into sickle cell red blood cells via activation of the TRPV2 channel.

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).

Exhaled Aldehydes as Biomarkers for Lung Diseases: A Narrative Review.

Breath analysis provides great potential as a fast and non-invasive diagnostic tool for several diseases. Straight-chain aliphatic aldehydes were repeatedly detected in the breath of patients suffering from lung diseases using a variety of methods, such as mass spectrometry, ion mobility spectrometry, or electro-chemical sensors. Several studies found increased concentrations of exhaled aldehydes in patients suffering from lung cancer, inflammatory and infectious lung diseases, and mechanical lung injury. This article reviews the origin of exhaled straight-chain aliphatic aldehydes, available detection methods, and studies that found increased aldehyde exhalation in lung diseases.

Continuous Percoll Gradient Centrifugation of Erythrocytes-Explanation of Cellular Bands and Compromised Age Separation.

(1) Background: When red blood cells are centrifuged in a continuous Percoll-based density gradient, they form discrete bands. While this is a popular approach for red blood cell age separation, the mechanisms involved in banding were unknown. (2) Methods: Percoll centrifugations of red blood cells were performed under various experimental conditions and the resulting distributions analyzed. The age of the red blood cells was measured by determining the protein band 4.1a to 4.1b ratio based on western blots. Red blood cell aggregates, so-called rouleaux, were monitored microscopically. A mathematical model for the centrifugation process was developed. (3) Results: The red blood cell band pattern is reproducible but re-centrifugation of sub-bands reveals a new set of bands. This is caused by red blood cell aggregation. Based on the aggregation, our mathematical model predicts the band formation. Suppression of red blood cell aggregation reduces the band formation. (4) Conclusions: The red blood cell band formation in continuous Percoll density gradients could be explained physically by red blood cell aggregate formation. This aggregate formation distorts the density-based red blood cell age separation. Suppressing aggregation by osmotic swelling has a more severe effect on compromising the RBC age separation to a higher degree.

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.

Red blood cell shape transitions and dynamics in time-dependent capillary flows.

The dynamics of single red blood cells (RBCs) determine microvascular blood flow by adapting their shape to the flow conditions in the narrow vessels. In this study, we explore the dynamics and shape transitions of RBCs on the cellular scale under confined and unsteady flow conditions using a combination of microfluidic experiments and numerical simulations. Tracking RBCs in a comoving frame in time-dependent flows reveals that the mean transition time from the symmetric croissant to the off-centered, nonsymmetric slipper shape is significantly faster than the opposite shape transition, which exhibits pronounced cell rotations. Complementary simulations indicate that these dynamics depend on the orientation of the RBC membrane in the channel during the time-dependent flow. Moreover, we show how the tank-treading movement of slipper-shaped RBCs in combination with the narrow channel leads to oscillations of the cell's center of mass. The frequency of these oscillations depends on the cell velocity, the viscosity of the surrounding fluid, and the cytosol viscosity. These results provide a potential framework to identify and study pathological changes in RBC properties.

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.

Differential Response of Pentanal and Hexanal Exhalation to Supplemental Oxygen and Mechanical Ventilation in Rats.

High inspired oxygen during mechanical ventilation may influence the exhalation of the previously proposed breath biomarkers pentanal and hexanal, and additionally induce systemic inflammation. We therefore investigated the effect of various concentrations of inspired oxygen on pentanal and hexanal exhalation and serum interleukin concentrations in 30 Sprague Dawley rats mechanically ventilated with 30, 60, or 93% inspired oxygen for 12 h. Pentanal exhalation did not differ as a function of inspired oxygen but increased by an average of 0.4 (95%CI: 0.3; 0.5) ppb per hour, with concentrations doubling from 3.8 (IQR: 2.8; 5.1) ppb at baseline to 7.3 (IQR: 5.0; 10.8) ppb after 12 h. Hexanal exhalation was slightly higher at 93% of inspired oxygen with an average difference of 0.09 (95%CI: 0.002; 0.172) ppb compared to 30%. Serum IL-6 did not differ by inspired oxygen, whereas IL-10 at 60% and 93% of inspired oxygen was greater than with 30%. Both interleukins increased over 12 h of mechanical ventilation at all oxygen concentrations. Mechanical ventilation at high inspired oxygen promotes pulmonary lipid peroxidation and systemic inflammation. However, the response of pentanal and hexanal exhalation varies, with pentanal increasing by mechanical ventilation, whereas hexanal increases by high inspired oxygen concentrations.

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.

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.

Exhaled Propofol Concentrations Correlate With Plasma and Brain Tissue Concentrations in Rats.

BACKGROUND: Propofol can be measured in exhaled gas. Exhaled and plasma propofol concentrations correlate well, but the relationship with tissue concentrations remains unknown. We thus evaluated the relationship between exhaled, plasma, and various tissue propofol concentrations. Because the drug acts in the brain, we focused on the relationship between exhaled and brain tissue propofol concentrations. METHODS: Thirty-six male Sprague-Dawley rats were anesthetized with propofol, ketamine, and rocuronium for 6 hours. Animals were randomly assigned to propofol infusions at 20, 40, or 60 mg·kg·h (n = 12 per group). Exhaled propofol concentrations were measured at 15-minute intervals by multicapillary column-ion mobility spectrometry. Arterial blood samples, 110 µL each, were collected 15, 30, and 45 minutes, and 1, 2, 4, and 6 hours after the propofol infusion started. Propofol concentrations were measured in brain, lung, liver, kidney, muscle, and fat tissue after 6 hours. The last exhaled and plasma concentrations were used for linear regression analyses with tissue concentrations. RESULTS: The correlation of exhaled versus plasma concentrations (R = 0.71) was comparable to the correlation of exhaled versus brain tissue concentrations (R = 0.75) at the end of the study. In contrast, correlations between plasma and lung and between lung and exhaled propofol concentrations were poor. Less than a part-per-thousand of propofol was exhaled over 6 hours. CONCLUSIONS: Exhaled propofol concentrations correlate reasonably well with brain tissue and plasma concentrations in rats, and may thus be useful to estimate anesthetic drug effect. The equilibration between plasma propofol and exhaled gas is apparently independent of lung tissue concentration. Only a tiny fraction of administered propofol is eliminated via the lungs, and exhaled quantities thus have negligible influence on plasma concentrations.

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.

Exhaled Volatile Organic Compounds during Inflammation Induced by TNF-α in Ventilated Rats.

Systemic inflammation alters the composition of exhaled breath, possibly helping clinicians diagnose conditions such as sepsis. We therefore evaluated changes in exhaled breath of rats given tumor necrosis factor-alpha (TNF-α). Thirty male Sprague-Dawley rats were randomly assigned to three groups (n = 10 each) with intravenous injections of normal saline (control), 200 µg·kg-1 bodyweight TNF-α (TNF-α-200), or 600 µg·kg-1 bodyweight TNF-α (TNF-α-600), and were observed for 24 h or until death. Animals were ventilated with highly-purified synthetic air to analyze exhaled air by multicapillary column-ion mobility spectrometry. Volatile organic compounds (VOCs) were identified from a database. We recorded blood pressure and cardiac output, along with cytokine plasma concentrations. Control rats survived the 24 h observation period, whereas mean survival time decreased to 22 h for TNF-α-200 and 23 h for TNF-α-600 rats. Mean arterial pressure decreased in TNF-α groups, whereas IL-6 increased, consistent with mild to moderate inflammation. Hundreds of VOCs were detected in exhalome. P-cymol increased by a factor-of-two 4 h after injection of TNF-α-600 compared to the control and TNF-α-200. We found that 1-butanol and 1-pentanol increased in both TNF-α groups after 20 h compared to the control. As breath analysis distinguishes between two doses of TNF-α and none, we conclude that it might help clinicians identify systemic inflammation.

Stability of Propofol (2,6-Diisopropylphenol) in Thermal Desorption Tubes during Air Transport.

The anesthetic propofol and other exhaled organic compounds can be sampled in Tenax sorbent tubes and analyzed by gas chromatography coupled with mass spectrometry. The aim of this study was to evaluate the stability of propofol in Tenax sorbent tubes during overseas shipping. This is relevant for international pharmacokinetic studies on propofol in exhaled air. Tenax sorbent tube propofol samples with concentrations between 10 and 100 ng were prepared by liquid injection and with a calibration gas generator. For each preparation method, one reference set was analyzed immediately after preparation, a second set was stored at room temperature, and a third one was stored refrigerated. The fourth set was sent from Germany by airmail to USA and back. The shipped set of tubes was analyzed when it returned after 55 days elapsed. Then, the room temperature samples and the refrigerated stored samples were also analyzed. To evaluate the stability of propofol in the stored and shipped tubes, we calculated the recovery rates of each sample set. The mean recovery in the stored samples was 101.2% for the liquid preparation and 134.6% for the gaseous preparation at 4°C. At 22°C, the recovery was 96.1% for liquid preparation and 92.1% for gaseous preparation, whereas the shipped samples had a recovery of 85.3% and 111.3%. Thus, the deviation of the shipped samples is within a range of 15%, which is analytically acceptable. However, the individual values show significantly larger deviations of up to -32.1% (liquid) and 30.9% (gaseous). We conclude that storage of propofol on Tenax tubes at room temperature for 55 days is possible to obtain acceptable results. However, it appears that due to severe temperature and pressure variations air shipment of propofol samples in Tenax tubes without cooling shows severe deviations from the initial concentration. Although it was not tested in this study, we assume that refrigerated transport might be necessary to obtain comparable results as in the stored samples.

Simultaneous quantification of propofol, ketamine and rocuronium in just 10 µL plasma using liquid chromatography coupled with quadrupole mass spectrometry and its pilot application to a pharmacokinetic study in rats.

The combination of propofol, ketamine and rocuronium can be used for anesthesia of ventilated rats. However, reliable pharmacokinetic models of these drugs have yet to be developed in rats, and consequently optimal infusion strategies are also unknown. Development of pharmacokinetic models requires repeated measurements of drug concentrations. In small animals, samples must be tiny to avoid excessing blood extraction. We therefore developed a drug assay system using high-performance liquid chromatography coupled with quadrupole mass spectrometry that simultaneously determines the concentration of all three drugs in just 10 µL rat plasma. We established a plasma extraction protocol, using acetonitrile as the precipitating reagent. Calibration curves were linear with R2 = 0.99 for each drug. Mean recovery from plasma was 91-93% for propofol, 89-93% for ketamine and 90-92% for rocuronium. The assay proved to be accurate for propofol 4.1-8.3%, ketamine 1.9-7.8% and rocuronium -3.6-4.7% relative error. The assay was also precise; the intra-day precisions were propofol 2.0-4.0%, ketamine 2.7-2.9% and rocuronium 2.9-3.3% relative standard deviation. Finally, the method was successfully applied to measurement the three drugs in rat plasma samples. Mean plasma concentrations with standard deviations were propofol 2.0 µg/mL ±0.5%, ketamine 3.9 µg/mL ±1.0% and rocuronium 3.2 µg/mL ±0.8% during ventilation.

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.