Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1102 New methods for optimization of mechanical ventilation PETER KOSTIC ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-554-9238-0 UPPSALA urn:nbn:se:uu:diva-249172 2015 Dissertation presented at Uppsala University to be publicly examined in Enghoffsalen, Entrance 50, Akademiska sjukhuset, Uppsala, Wednesday, 3 June 2015 at 09:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in Swedish. Faculty examiner: Johan Petersson (Karolinska institutet, Institutionen för fysiologi och farmakologi, Anestesiologi och intensivvård). Abstract Kostic, P. 2015. New methods for optimization of mechanical ventilation. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1102. 62 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9238-0. Mechanical ventilation saves lives, but it is an intervention fraught with the potential for serious complications. Prevention of these complications has become the focus of research and critical care in the last twenty years. This thesis presents the first use, or the application under new conditions, of three technologies that could contribute to optimization of mechanical ventilation. Optoelectronic plethysmography was used in Papers I and II for continuous assessment of changes in chest wall volume, configuration, and motion in the perioperative period. A forced oscillation technique (FOT) was used in Paper III to evaluate a novel positive end-expiratory pressure (PEEP) optimization strategy. Finally, in Paper IV, FOT in conjunction with an optical sensor based on a self-mixing laser interferometer (LIR) was used to study the oscillatory mechanics of the respiratory system and to measure the chest wall displacement. In Paper I, propofol anesthesia decreased end-expiratory chest wall volume (VeeCW) during induction, with a more pronounced effect on the abdominal compartment than on the rib cage. The main novel findings were an increased relative contribution of the rib cage to ventilation after induction of anesthesia, and the fact that the rib cage initiates post-apneic ventilation. In Paper II, a combination of recruitment maneuvers, PEEP, and reduced fraction of inspired oxygen, was found to preserve lung volume during and after anesthesia. Furthermore, the decrease in VeeCW during emergence from anesthesia, associated with activation of the expiratory muscles, suggested that active expiration may contribute to decreased functional residual capacity, during emergence from anesthesia. In the lavage model of lung injury studied in Paper III, a PEEP optimization strategy based on maximizing oscillatory reactance measured by FOT resulted in improved lung mechanics, increased oxygenation, and reduced histopathologic evidence of ventilator-induced lung injury. Paper IV showed that it is possible to apply both FOT and LIR simultaneously in various conditions ranging from awake quiet breathing to general anesthesia with controlled mechanical ventilation. In the case of LIR, an impedance map representing different regions of the chest wall showed reproducible changes during the different stages that suggested a high sensitivity of the LIR-based measurements. Keywords: mechanical ventilation, optoelectronic plethysmography, forced oscillation technique, laser interferometry Peter Kostic, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Akademiska sjukhuset, Uppsala University, SE-75185 Uppsala, Sweden. © Peter Kostic 2015 ISSN 1651-6206 ISBN 978-91-554-9238-0 urn:nbn:se:uu:diva-249172 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-249172) To my family List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Aliverti, A., Kostic, P., Lo Mauro, A., Andersson-Olerud, M., Quaranta, M., Pedotti, A., Hedenstierna, G., Frykholm, P. (2011) Effects of propofol anaesthesia on thoraco-abdominal volume variation during spontaneous breathing and mechanical ventilation. Acta Anaesthesiol Scand, 55(5):588-96 II Kostic, P., Lo Mauro, A., Larsson, A., Pedotti, A., Hedenstier- na, G., Frykholm, P., Aliverti, A. (2014) Active expiration may contribute to the reduction in end-expiratory volume during emergence from anesthesia and in the immediate post-operative period. In manuscript III Kostic, P., Zannin, E., Andersson-Olerud, M., Pompilio, P.P., Hedenstierna, G., Pedotti, A., Larsson, A., Frykholm, P., Del- laca, R. (2011) Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury: a controlled experimental study in pigs with saline lavage injury. Crit Care, 15(3):R126 IV Kostic, P., Milesi, I., Zannin, E., Larsson, A., Frykholm, P., Dellaca, R.L. (2015) The application of forced oscillation tech- nique and self-mixing laser interferometer during anesthesia and mechanical ventilation. In manuscript Reprints were made with permission from the respective publishers. Contents Introduction ................................................................................................... 11 Background ................................................................................................... 13 Mechanical ventilation and ventilator-induced lung injury ...................... 13 Protective lung ventilation ........................................................................ 13 Forced oscillation technique ..................................................................... 15 Experimental setup ............................................................................... 16 Laser interferometry ................................................................................. 17 Experimental setup ............................................................................... 17 Effects of anesthesia on respiratory function and anesthesia-induced atelectasis .................................................................................................. 18 Anesthesia and postoperative pulmonary complications .......................... 19 Lung-protective ventilation strategy during anesthesia and the perioperative period .................................................................................. 20 Optoelectronic plethysmography .............................................................. 22 Aims .............................................................................................................. 24 Materials and methods .................................................................................. 25 Papers I and II ........................................................................................... 25 Patients ................................................................................................. 25 Anesthesia ............................................................................................ 25 Protocol ................................................................................................ 26 Data analysis ........................................................................................ 28 Paper III .................................................................................................... 29 Animal model and preparation ............................................................. 29 Protocol ................................................................................................ 29 Data analysis ........................................................................................ 30 Paper IV .................................................................................................... 30 Patients ................................................................................................. 31 Anesthesia ............................................................................................ 31 Protocol ................................................................................................ 31 Data analysis ........................................................................................ 31 Statistical analysis (Papers I-IV) .......................................................... 32 Results ........................................................................................................... 33 Paper I ....................................................................................................... 33 Paper II ..................................................................................................... 36 Paper III .................................................................................................... 39 Paper IV .................................................................................................... 42 Discussion ..................................................................................................... 45 Main findings ............................................................................................ 45 Papers I and II ........................................................................................... 45 Paper III .................................................................................................... 47 Paper IV .................................................................................................... 49 Conclusions ................................................................................................... 50 Limitations ...................................................................................................