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Heart-Lung Interactions: Implications for Non-Invasive Evaluation of Changes in Blood Volume

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Heart-Lung Interactions: Implications for Non-Invasive Evaluation of Changes in Blood Volume 1 Heart-lung interactions: Implications for non-invasive evaluation of changes in blood volume Thesis for the degree of Philosophiae Doctor (PhD) Cand. Med. Ingrid Elise Hoff Institute of Clinical Medicine, Faculty of Medicine University of Oslo Oslo, Norway and The Norwegian Air Ambulance Foundation Oslo, Norway and Department of Anaesthesiology Division of Emergencies and Critical Care Oslo University Hospital Oslo, Norway 2019 2 © Ingrid Elise Hoff , 2019 Series of dissertations submitted to the Faculty of Medicine, University of Oslo ISBN 978-82-8377-539-6 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission. Cover: Hanne Baadsgaard Utigard. Print production: Reprosentralen, University of Oslo. 3 To Ingvild and Benedikte 4 5 Table of Contents 1 ACKNOWLEDGEMENTS ............................................................................................ 9 2 ABBREVIATIONS AND ACRONYMS ..................................................................... 11 3 LIST OF PAPERS ......................................................................................................... 13 4 SYNOPSIS .................................................................................................................... 14 5 INTRODUCTION ......................................................................................................... 17 5.1 Why normovolaemia? Oxygen delivery and consumption .................................... 17 5.2 Cardiac output and cardiac output measurement ................................................... 18 5.3 Venous return and the Frank-Starling-curve .......................................................... 20 5.4 Haemodynamic effects of respiration .................................................................... 24 5.5 Dynamic variables and the concept of fluid responsiveness.................................. 26 5.6 Pulse pressure variations (∆PP) .......................................................................... 27 5.6.1 Considerations for the use ∆PP for haemodynamic evaluation ......................... 29 5.6.1.1 Ventilation ...................................................................................................... 29 5.6.1.2 Intraabdominal hypertension .......................................................................... 30 5.6.1.3 Cardiac dysfunction ........................................................................................ 31 5.7 The photoplethysmographic waveform amplitude variation (∆POP), perfusion index (PI) and pleth variability index (PVI) ..................................................................... 31 5.7.1 Limitations to the use of ∆POP, PVI and PI for haemodynamic evaluation ..... 33 5.7.1.1 Vascular tone .................................................................................................. 33 5.7.1.2 Processing algorithms ..................................................................................... 34 5.8 End-tidal (EtCO2) and volumetric (VtCO2) carbon dioxide .................................. 35 5.8.1 Limitations of EtCO2 and VtCO2 for haemodynamic evaluation ...................... 38 6 AIM AND RESEARCH QUESTIONS ........................................................................ 39 7 MATERIAL AND METHODS .................................................................................... 40 7.1 Study populations ................................................................................................... 40 7.2 Lower Body Negative Pressure (LBNP) ................................................................ 40 7.3 Right ventricular pacing (RVP) ............................................................................. 42 7.4 Passive leg raise (PLR) .......................................................................................... 43 7.5 Modification of respiration: Non-invasive positive pressure ventilation (NPPV), continuous positive airway pressure (CPAP) and positive expiratory pressure (PEP) ..... 44 7.6 Cardiac output measurements ................................................................................ 45 6 7.7 The volume-clamp method for blood pressure measurement ................................ 46 7.8 Sampling of haemodynamic data ........................................................................... 47 7.9 Calculation of respiratory variations in pulse pressure (∆PP) and the photoplethysmographic waveform amplitude (∆POP) ..................................................... 47 7.10 Calculation of end-tidal (EtCO2) and volumetric (VtCO2) carbon dioxide ........... 49 7.11 Statistical methods ................................................................................................. 50 7.11.1 Linear mixed models .......................................................................................... 50 7.11.2 Correlation .......................................................................................................... 51 7.11.3 Receiver operating characteristics plot (ROC-plot) ........................................... 52 8 RESULTS ...................................................................................................................... 54 8.1 Study I .................................................................................................................... 54 8.2 Study II ................................................................................................................... 54 8.3 Study III ................................................................................................................. 55 9 DISCUSSION ............................................................................................................... 56 9.1 Main results ............................................................................................................ 56 9.1.1 The ability of ∆PP, ∆POP, PVI and PI to reflect hypovolaemia during spontaneous breathing and non-invasive positive pressure ventilation (NPPV) .............. 56 9.1.2 The ability of EtCO2 and VtCO2 to reflect hypovolaemia ................................. 59 9.1.3 The ability of ∆PP and ∆POP to detect hypovolaemia during positive expiratory pressure (PEP) and continuous positive airway pressure (CPAP) .................................... 63 9.2 Methodological considerations .............................................................................. 66 9.2.1 Study populations ............................................................................................... 66 9.2.1.1 Choice of study populations ........................................................................... 66 9.2.1.2 Sample size calculation .................................................................................. 67 9.2.1.3 Randomisation ................................................................................................ 69 9.2.2 Models ................................................................................................................ 69 9.2.2.1 Lower body negative pressure (LBNP) as a model of central hypovolaemia 69 9.2.2.2 Non-invasive positive pressure ventilation (NPPV) to induce respiratory variations in stroke volume ............................................................................................... 70 9.2.2.3 Right ventricular pacing for the reduction of cardiac output .......................... 71 9.2.3 Measurements and calculations: Sources of potential errors ............................. 71 9.2.4 Statistical methods .............................................................................................. 74 9.2.4.1 Linear mixed models ...................................................................................... 74 9.2.4.2 Correlation ...................................................................................................... 75 7 9.2.4.3 Receiver operating characteristics (ROC) plots ............................................. 75 9.3 Ethical considerations ............................................................................................ 76 9.4 Future perspectives ................................................................................................ 77 10 CONCLUSIONS ....................................................................................................... 79 11 REFERENCES .......................................................................................................... 80 12 PAPERS ..................................................................................................................... 89 8 9 1 ACKNOWLEDGEMENTS First and foremost, I want to thank my supervisors Knut Arvid Kirkebøen, Svein Aslak Landsverk and Lars Øivind Høiseth for giving me the opportunity to work within the field of research. This group of supervisors is small, but highly efficient; consisting of different members who complement each other perfectly and thus cater to a PhD-student`s every need. This work required custom-made technology that demanded some unusual skills, and practical as well as theoretical advice has been provided swiftly and at all hours, for which I am very grateful. Many thanks also to The Norwegian Air Ambulance Foundation and its donors who have made this work possible through educational, practical and financial support. It has been a privilege being one of your PhD-students, and I`m very grateful to Hans Morten Lossius who originally invited me into this community
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