While protecting against the coronavirus transmission, face-masks may have adverse effects on res... more While protecting against the coronavirus transmission, face-masks may have adverse effects on respiratory-haemodynamic parameters. We investigated immediate and progressive effects of FFP2 and surgical masks on exhaled breath constituents and physiological attributes in 30 healthy volunteers at rest. We continuously monitored exhaled breath profiles in the mask space in elderly (age: 60–80 years) and adults (age: 20–60 years) over a period of 30 min by high-resolution real-time mass-spectrometry (PTR-ToF-MS). Peripheral oxygen saturation, respiratory- and haemodynamic parameters were measured (non-invasively) continuously in parallel. Profound and consistent decrease in SpO2 and increase in pET-CO2 indicates ascending deoxygenation and inadequate ventilation in subjects. Cardiac output and MAP changed as secondary. Exhalation of blood-borne volatile metabolites mirrored behaviour of cardiac output, MAP, SpO2, respiratory rate and pET-CO2. FFP2 masks affected more pronouncedly than s...
Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabd... more Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabdominal aortic aneurysms. For prevention and early treatment of spinal ischemia, intraoperative monitoring of spinal cord integrity is essential. This study was intended to improve recognition of SCI through a combination of transcranial motor-evoked potentials (tc-MEPs), serum markers, and innovative breath analysis. In 9 female German Landrace pigs, tc-MEPs were captured, markers of neuronal damage were determined in blood, and volatile organic compounds (VOCs) were analyzed in exhaled air. After thoraco-phrenico-laparotomy, SCI was initiated through sequential clamping (n = 4) or permanently ligating (n = 5) SAs of the abdominal and thoracic aorta in caudocranial orientation until a drop in the tc-MEPs to at least 25% of the baseline was recorded. VOCs in breath were determined by means of solid-phase microextraction coupled with gas chromatography-mass spectrometry. After waking up, c...
Breath analysis not only holds great potential for the development of new non-invasive diagnostic... more Breath analysis not only holds great potential for the development of new non-invasive diagnostic methods, but also for the identification and follow up of drug levels in breath. This is of interest for both, forensic and medical science. On the one hand, the detection of drugs of abuse in exhaled breath-similar to the well-known breath alcohol tests-would be highly desirable as an alternative to blood or urine analysis in situations such as police controls for drugged driving. The non-invasive detection of drugs and their metabolites is thus of great interest in forensic science, especially since marijuana is becoming legalized in certain parts of the US and the EU. The detection and monitoring of medical drugs in exhaled breath without the need of drawing blood samples on the other hand, is of high relevance in the clinical environment. This could facilitate a more precise medication and enable therapy control without any burden to the patient. Furthermore, it could be a step towa...
Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibre... more Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibres introduced directly into the blood stream. This study was intended to extend this technique to a clinically relevant antibiotic drug under close to physiological conditions in human blood. An artificial vein system was built up from heart and lung machine components. Determination of Linezolid (0-15 mug/mL) was performed by SPME from the flowing system ("online", flow velocities 2-50 cm/s), from blood withdrawn from the system ("offline") and by means of a SPE/HPLC method. SPME was done using new fibres ("new") for each analysis, and in the way that one fibre was reused ("re") for one series of measurements. Drug SPME did not depend on blood flow velocities. Linear regression of data (concentration vs. amount extracted) yielded R(2)=0.998 for SPE/HPLC, R(2)=0.955 for SPME(online_new), 0.929 for SPME(online_re), 0.929 SPME(offline_new), 0.973 for SPME(offline_re), RSD were 52% (SPME(online_new)), 10% (SPME(online_re)), 47% (SPME(offline_new)), 18% (SPME(offline_re)), 8% (SPE/HPLC). In-vein SPME has the potential to minimize blood requirement for diagnostic purposes and to speed up analysis of clinically relevant drugs, if inter-fibre variation can be reduced through standardized manufacturing.
Introduction: Oxygenated compounds such as aldehydes and ketones in breath have been described as... more Introduction: Oxygenated compounds such as aldehydes and ketones in breath have been described as biomarkers of metabolism, oxidative stress and cancer. Conventional analysis of these compounds in the low parts per billion (ppb) range is hampered by their reactivity and poor stability. Sampling and preconcentration of volatile substances are crucial issues in breath analysis. Thus, reliable and easy to use techniques are mandatory for clinical application. Micro-extraction techniques such as Needle Trap Devices (NTDs), Solid Phase Micro Extraction (SPME) and Solid Phase Micro Extraction with On Fiber Derivatization (SPME-OFD) have recently been proposed for this purpose. Aim: This study was intended to evaluate different methods of sample preparation and preconcentration with respect to applicability of breath analysis under real life clinical conditions. Methods: After approval by the local ethics committee, 10 patients planned to undergo cardiac surgery with extracorporeal circula...
The use of toxic antifoulants is a worldwide applied procedure for the prevention of biofouling. ... more The use of toxic antifoulants is a worldwide applied procedure for the prevention of biofouling. The substitution of antifouling toxins by naturally produced antifouling agents isolated from plants and animals was described.
Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibre... more Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibres introduced directly into the blood stream. This study was intended to extend this technique to a clinically relevant antibiotic drug under close to physiological conditions in human blood. An artificial vein system was built up from heart and lung machine components. Determination of Linezolid (0-15 mug/mL) was performed by SPME from the flowing system ("online", flow velocities 2-50 cm/s), from blood withdrawn from the system ("offline") and by means of a SPE/HPLC method. SPME was done using new fibres ("new") for each analysis, and in the way that one fibre was reused ("re") for one series of measurements. Drug SPME did not depend on blood flow velocities. Linear regression of data (concentration vs. amount extracted) yielded R(2)=0.998 for SPE/HPLC, R(2)=0.955 for SPME(online_new), 0.929 for SPME(online_re), 0.929 SPME(offline_new), 0.973 for SPME(offline_re), RSD were 52% (SPME(online_new)), 10% (SPME(online_re)), 47% (SPME(offline_new)), 18% (SPME(offline_re)), 8% (SPE/HPLC). In-vein SPME has the potential to minimize blood requirement for diagnostic purposes and to speed up analysis of clinically relevant drugs, if inter-fibre variation can be reduced through standardized manufacturing.
Breath analysis could offer a non-invasive means of drug monitoring if adequate analytical method... more Breath analysis could offer a non-invasive means of drug monitoring if adequate analytical methods and robust correlations between drug concentrations in breath and blood can be established. We therefore applied headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) to assess breath and blood concentrations of the intravenous drug propofol in patients under anesthesia or sedation. Arterial, central- and peripheral-venous blood and alveolar breath samples were drawn in parallel from 16 mechanically ventilated patients. In addition, six patients undergoing lung resection were investigated. Substances were preconcentrated by means of HS-SPME, separated by GC and identified by MS. Propofol detection limits were 0.006 nmol/L in breath and 72.20 nmol/L in blood, the quantitation limits were 0.009 nmol/L and 75.89 nmol/L (end tidal breath/blood). Intraday precision was 8-11%, recovery 97-103%. Propofol concentrations were 0.04-0.5 nmol/L in breath and 2-120 micromol/L in blood. Only arterial propofol concentrations showed a correlation with concentrations in breath. Impaired ventilation/perfusion ratios in patients under lung resection resulted in changes of correlation coefficients. Reliable and precise analytical methods such as HS-SPME-GC-MS represent basic requirements if breath analysis is to be set up for non-invasive monitoring of intravenous drugs and control of anesthesia.
Contemporary resuscitation guidelines for basic life support recommend an immediate onset of card... more Contemporary resuscitation guidelines for basic life support recommend an immediate onset of cardiac compressions in case of cardiac arrest followed by rescue breaths. Effective ventilation is often omitted due to fear of doing harm and fear of infectious diseases. In order to improve ventilation a pre-stage of an automatic respirator was developed for use by laypersons. Fifty-two healthy volunteers were ventilated by means of a prototype respirator via a full-face mask in a pilot study. The pre-stage public access ventilator (PAV) consisted of a low-cost self-designed turbine, with sensors for differential pressure, flow, FO2, FCO2 and 3-axis acceleration measurement. Sensor outputs were used to control the respirator and to recognize conditions relevant for efficiency of ventilation and patients' safety. Different respiratory manoeuvres were applied: a) pressure controlled ventilation (PCV), b) PCV with controlled leakage and c) PCV with simulated airway occlusion. Sensor sign...
Patients with end-stage renal disease (ESRD) are at risk for a numerous complications. This study... more Patients with end-stage renal disease (ESRD) are at risk for a numerous complications. This study was intended to evaluate breath analysis for monitoring and therapy initiation under haemodialysis (HD). Exhaled alveolar air from 30 ESRD patients during 4 h thrice-weekly HD was analysed by means of HS-SPME-GC-MS. Venous blood samples were taken for determination of conventional serum parameters. Exhaled concentrations of isoprene (10-589 ppbV) were dropped at initiation of HD and increased at the end of HD. Isoprene concentration changes were similar to changes of serum LDH activities. Variation of exhaled acetone concentrations (59 to 8509 ppbV) was significantly lower in diabetic patients when compared to non-diabetics. Exhaled pentane (0.3 to 12 ppbV) increased at onset of HD and returned to baseline levels afterwards. Benzene concentrations showed typical washout characteristics. Ethanol and DMS concentrations remained constant during HD. Breath analysis can be used to recognize oxidative stress, metabolic conditions and haemolysis during HD. Hence, non-invasive breath testing could be used to monitor ESRD patients under HD and prevent them from being affected by well-known detrimental side effects of renal replacement therapy.
While protecting against the coronavirus transmission, face-masks may have adverse effects on res... more While protecting against the coronavirus transmission, face-masks may have adverse effects on respiratory-haemodynamic parameters. We investigated immediate and progressive effects of FFP2 and surgical masks on exhaled breath constituents and physiological attributes in 30 healthy volunteers at rest. We continuously monitored exhaled breath profiles in the mask space in elderly (age: 60–80 years) and adults (age: 20–60 years) over a period of 30 min by high-resolution real-time mass-spectrometry (PTR-ToF-MS). Peripheral oxygen saturation, respiratory- and haemodynamic parameters were measured (non-invasively) continuously in parallel. Profound and consistent decrease in SpO2 and increase in pET-CO2 indicates ascending deoxygenation and inadequate ventilation in subjects. Cardiac output and MAP changed as secondary. Exhalation of blood-borne volatile metabolites mirrored behaviour of cardiac output, MAP, SpO2, respiratory rate and pET-CO2. FFP2 masks affected more pronouncedly than s...
Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabd... more Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabdominal aortic aneurysms. For prevention and early treatment of spinal ischemia, intraoperative monitoring of spinal cord integrity is essential. This study was intended to improve recognition of SCI through a combination of transcranial motor-evoked potentials (tc-MEPs), serum markers, and innovative breath analysis. In 9 female German Landrace pigs, tc-MEPs were captured, markers of neuronal damage were determined in blood, and volatile organic compounds (VOCs) were analyzed in exhaled air. After thoraco-phrenico-laparotomy, SCI was initiated through sequential clamping (n = 4) or permanently ligating (n = 5) SAs of the abdominal and thoracic aorta in caudocranial orientation until a drop in the tc-MEPs to at least 25% of the baseline was recorded. VOCs in breath were determined by means of solid-phase microextraction coupled with gas chromatography-mass spectrometry. After waking up, c...
Breath analysis not only holds great potential for the development of new non-invasive diagnostic... more Breath analysis not only holds great potential for the development of new non-invasive diagnostic methods, but also for the identification and follow up of drug levels in breath. This is of interest for both, forensic and medical science. On the one hand, the detection of drugs of abuse in exhaled breath-similar to the well-known breath alcohol tests-would be highly desirable as an alternative to blood or urine analysis in situations such as police controls for drugged driving. The non-invasive detection of drugs and their metabolites is thus of great interest in forensic science, especially since marijuana is becoming legalized in certain parts of the US and the EU. The detection and monitoring of medical drugs in exhaled breath without the need of drawing blood samples on the other hand, is of high relevance in the clinical environment. This could facilitate a more precise medication and enable therapy control without any burden to the patient. Furthermore, it could be a step towa...
Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibre... more Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibres introduced directly into the blood stream. This study was intended to extend this technique to a clinically relevant antibiotic drug under close to physiological conditions in human blood. An artificial vein system was built up from heart and lung machine components. Determination of Linezolid (0-15 mug/mL) was performed by SPME from the flowing system ("online", flow velocities 2-50 cm/s), from blood withdrawn from the system ("offline") and by means of a SPE/HPLC method. SPME was done using new fibres ("new") for each analysis, and in the way that one fibre was reused ("re") for one series of measurements. Drug SPME did not depend on blood flow velocities. Linear regression of data (concentration vs. amount extracted) yielded R(2)=0.998 for SPE/HPLC, R(2)=0.955 for SPME(online_new), 0.929 for SPME(online_re), 0.929 SPME(offline_new), 0.973 for SPME(offline_re), RSD were 52% (SPME(online_new)), 10% (SPME(online_re)), 47% (SPME(offline_new)), 18% (SPME(offline_re)), 8% (SPE/HPLC). In-vein SPME has the potential to minimize blood requirement for diagnostic purposes and to speed up analysis of clinically relevant drugs, if inter-fibre variation can be reduced through standardized manufacturing.
Introduction: Oxygenated compounds such as aldehydes and ketones in breath have been described as... more Introduction: Oxygenated compounds such as aldehydes and ketones in breath have been described as biomarkers of metabolism, oxidative stress and cancer. Conventional analysis of these compounds in the low parts per billion (ppb) range is hampered by their reactivity and poor stability. Sampling and preconcentration of volatile substances are crucial issues in breath analysis. Thus, reliable and easy to use techniques are mandatory for clinical application. Micro-extraction techniques such as Needle Trap Devices (NTDs), Solid Phase Micro Extraction (SPME) and Solid Phase Micro Extraction with On Fiber Derivatization (SPME-OFD) have recently been proposed for this purpose. Aim: This study was intended to evaluate different methods of sample preparation and preconcentration with respect to applicability of breath analysis under real life clinical conditions. Methods: After approval by the local ethics committee, 10 patients planned to undergo cardiac surgery with extracorporeal circula...
The use of toxic antifoulants is a worldwide applied procedure for the prevention of biofouling. ... more The use of toxic antifoulants is a worldwide applied procedure for the prevention of biofouling. The substitution of antifouling toxins by naturally produced antifouling agents isolated from plants and animals was described.
Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibre... more Promising results in animals have shown the diagnostic potential of polypyrrole coated SPME fibres introduced directly into the blood stream. This study was intended to extend this technique to a clinically relevant antibiotic drug under close to physiological conditions in human blood. An artificial vein system was built up from heart and lung machine components. Determination of Linezolid (0-15 mug/mL) was performed by SPME from the flowing system ("online", flow velocities 2-50 cm/s), from blood withdrawn from the system ("offline") and by means of a SPE/HPLC method. SPME was done using new fibres ("new") for each analysis, and in the way that one fibre was reused ("re") for one series of measurements. Drug SPME did not depend on blood flow velocities. Linear regression of data (concentration vs. amount extracted) yielded R(2)=0.998 for SPE/HPLC, R(2)=0.955 for SPME(online_new), 0.929 for SPME(online_re), 0.929 SPME(offline_new), 0.973 for SPME(offline_re), RSD were 52% (SPME(online_new)), 10% (SPME(online_re)), 47% (SPME(offline_new)), 18% (SPME(offline_re)), 8% (SPE/HPLC). In-vein SPME has the potential to minimize blood requirement for diagnostic purposes and to speed up analysis of clinically relevant drugs, if inter-fibre variation can be reduced through standardized manufacturing.
Breath analysis could offer a non-invasive means of drug monitoring if adequate analytical method... more Breath analysis could offer a non-invasive means of drug monitoring if adequate analytical methods and robust correlations between drug concentrations in breath and blood can be established. We therefore applied headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) to assess breath and blood concentrations of the intravenous drug propofol in patients under anesthesia or sedation. Arterial, central- and peripheral-venous blood and alveolar breath samples were drawn in parallel from 16 mechanically ventilated patients. In addition, six patients undergoing lung resection were investigated. Substances were preconcentrated by means of HS-SPME, separated by GC and identified by MS. Propofol detection limits were 0.006 nmol/L in breath and 72.20 nmol/L in blood, the quantitation limits were 0.009 nmol/L and 75.89 nmol/L (end tidal breath/blood). Intraday precision was 8-11%, recovery 97-103%. Propofol concentrations were 0.04-0.5 nmol/L in breath and 2-120 micromol/L in blood. Only arterial propofol concentrations showed a correlation with concentrations in breath. Impaired ventilation/perfusion ratios in patients under lung resection resulted in changes of correlation coefficients. Reliable and precise analytical methods such as HS-SPME-GC-MS represent basic requirements if breath analysis is to be set up for non-invasive monitoring of intravenous drugs and control of anesthesia.
Contemporary resuscitation guidelines for basic life support recommend an immediate onset of card... more Contemporary resuscitation guidelines for basic life support recommend an immediate onset of cardiac compressions in case of cardiac arrest followed by rescue breaths. Effective ventilation is often omitted due to fear of doing harm and fear of infectious diseases. In order to improve ventilation a pre-stage of an automatic respirator was developed for use by laypersons. Fifty-two healthy volunteers were ventilated by means of a prototype respirator via a full-face mask in a pilot study. The pre-stage public access ventilator (PAV) consisted of a low-cost self-designed turbine, with sensors for differential pressure, flow, FO2, FCO2 and 3-axis acceleration measurement. Sensor outputs were used to control the respirator and to recognize conditions relevant for efficiency of ventilation and patients' safety. Different respiratory manoeuvres were applied: a) pressure controlled ventilation (PCV), b) PCV with controlled leakage and c) PCV with simulated airway occlusion. Sensor sign...
Patients with end-stage renal disease (ESRD) are at risk for a numerous complications. This study... more Patients with end-stage renal disease (ESRD) are at risk for a numerous complications. This study was intended to evaluate breath analysis for monitoring and therapy initiation under haemodialysis (HD). Exhaled alveolar air from 30 ESRD patients during 4 h thrice-weekly HD was analysed by means of HS-SPME-GC-MS. Venous blood samples were taken for determination of conventional serum parameters. Exhaled concentrations of isoprene (10-589 ppbV) were dropped at initiation of HD and increased at the end of HD. Isoprene concentration changes were similar to changes of serum LDH activities. Variation of exhaled acetone concentrations (59 to 8509 ppbV) was significantly lower in diabetic patients when compared to non-diabetics. Exhaled pentane (0.3 to 12 ppbV) increased at onset of HD and returned to baseline levels afterwards. Benzene concentrations showed typical washout characteristics. Ethanol and DMS concentrations remained constant during HD. Breath analysis can be used to recognize oxidative stress, metabolic conditions and haemolysis during HD. Hence, non-invasive breath testing could be used to monitor ESRD patients under HD and prevent them from being affected by well-known detrimental side effects of renal replacement therapy.
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