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Detecting Early Markers of Ventilator-Associated Pneumonia by Analysis of Exhaled Gas

Kunze-Szikszay, Nils, MD1; Walliser, Karoline, MD1; Luther, Jakob, MD1; Cambiaghi, Barbara, MD2; Reupke, Verena, DVM3; Dullin, Christian, Dr. sc. hum.4–6; Vautz, Wolfgang, Dr7,8; Bremmer, Felix, MD9; Telgheder, Ursula, Dr. rer. nat.10; Zscheppank, Cornelia, MSc10; Quintel, Michael, MD1; Perl, Thorsten, MD1,11

doi: 10.1097/CCM.0000000000003573
Online Laboratory Investigations

Objectives: The detection of microbial volatile organic compounds or host response markers in the exhaled gas could give an earlier diagnosis of ventilator-associated pneumonia. Gas chromatography-ion mobility spectrometry enables noninvasive, rapid, and sensitive analysis of exhaled gas. Using a rabbit model of ventilator-associated pneumonia we determined if gas chromatography-ion mobility spectrometry is able to detect 1) ventilator-associated pneumonia specific changes and 2) bacterial species-specific changes in the exhaled gas.

Design: Experimental in vivo study.

Setting: University research laboratory.

Subjects: Female New Zealand White rabbits.

Interventions: Animals were anesthetized and mechanically ventilated. To induce changes in the composition of exhaled gas we induced ventilator-associated pneumonia via endobronchial instillation of either Escherichia coli group (n = 11) or Pseudomonas aeruginosa group (n = 11) after 2 hours of mechanical ventilation. In a control group (n = 11) we instilled sterile lysogeny broth endobronchially.

Measurements and Main Results: Gas chromatography-ion mobility spectrometry gas analysis, CT scans of the lungs, and blood samples were obtained at four measurement points during the 10 hours of mechanical ventilation. The volatile organic compound patterns in the exhaled gas were compared and correlated with ventilator-associated pneumonia severity. Sixty-seven peak areas showed changes in signal intensity in the serial gas analyses. The signal intensity changes in 10 peak regions differed between the groups. Five peak areas (P_648_36, indole, P_714_278, P_700_549, and P_727_557) showed statistically significant changes of signal intensity.

Conclusions: This is the first in vivo study that shows the potential of gas chromatography-ion mobility spectrometry for early detection of ventilator-associated pneumonia specific volatile organic compounds and species differentiation by noninvasive analyses of exhaled gas.

1Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany.

2Reparto di anestesia e rianimazione, Ospedale San Gerardo Monza- Università degli studi di Milano- Bicocca, Italy.

3Central Animal Facility, University Medical Center, Göttingen, Germany.

4Institute for Diagnostic and Interventional Radiology, University Medical Center, University of Göttingen, Robert-Koch-Straße 40, Göttingen, Germany.

5Italian Synchrotron Light Source “Elettra,” Trieste, Italy.

6Max-Planck-Institute for Experimental Medicine, Herman-Rein-Str. 3, 37075 Göttingen, Germany.

7Leibniz-Institute for Analytical Sciences – ISAS – e.V., Bunsen-Kirchhoff-Straße 11, Dortmund, Germany.

8ION-GAS GmbH, Konrad-Adenauer-Allee 11, Dortmund, Germany.

9Institute for Pathology, University Medical Center, University of Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany.

10Department of Instrumental Analytical Chemistry, University of Duisburg-Essen, Universitätsstraße 5, Essen, Germany.

11Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany.

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Supported, in part, by a young investigators grant provided by the Medical Faculty of the Georg-August-University Göttingen.

Dr. Kunze-Szikszay’s institution received funding from Medical Faculty of the Georg-August-University Göttingen, and he received support for article research from Medical Faculty of the Georg-August-University Göttingen. Dr. Perl received funding from Humedics, The37°Company, and MSD Sharp and Dohme GmbH (Haar, Germany). The remaining authors have disclosed that they do not have any potential conflicts of interest.

This work was performed at the University Medical Centre of Göttingen, Göttingen, Germany.

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