High concentration oxygen therapy in acute respiratory disease

215 Pages·2010·2.59 MB·English

High concentration oxygen therapy in
acute respiratory disease

A thesis submitted in partial fulfilment
of the requirements for the Degree of
Doctor of Philosophy in Health Sciences
at the University of Canterbury

Kyle Perrin
University of Canterbury
2010
ii

Table of Contents
Table of Contents .............................................................................................................. ii
List of Figures ................................................................................................................... ix
List of Tables .................................................................................................................... xi
Acknowledgements ........................................................................................................ xiii
Abstract ............................................................................................................................ xv
Abbreviations and symbols .......................................................................................... xvii
Chapter 1: Introduction ................................................................................................... 1
1.1 The current approach to acute oxygen therapy ......................................................... 1
1.2 Uncontrolled oxygen in non-respiratory disease ...................................................... 3
1.3 Uncontrolled oxygen in respiratory disease .............................................................. 5
1.4 Thesis aim ................................................................................................................. 7
1.5 Thesis outline ............................................................................................................ 8
1.6 Definitions................................................................................................................. 9
Chapter 2: Background history and respiratory physiology ...................................... 11
2.1 The history of oxygen as a medical therapy ........................................................... 11
2.1.1 Discovery ......................................................................................................... 11
iii
2.1.2 Early attempts at therapy ................................................................................. 15
2.1.3 The modern era ................................................................................................ 17
2.2 Respiratory physiology ........................................................................................... 22
2.2.1 Pulmonary ventilation ...................................................................................... 23
2.2.2 Gas exchange ................................................................................................... 25
2.2.3 Ventilation-perfusion matching ....................................................................... 28
2.2.4 Hypoxic pulmonary vasoconstriction .............................................................. 30
2.2.5 Carbon dioxide elimination.............................................................................. 30
2.2.6 Physiological dead space ................................................................................. 32
Chapter 3: Oxygen therapy in acute respiratory disease ............................................ 35
3.1 COPD ...................................................................................................................... 35
3.1.1 Pathophysiology of acute exacerbations of COPD .......................................... 35
3.1.2 Oxygen therapy in AECOPD ........................................................................... 44
3.2 Asthma .................................................................................................................... 66
3.2.1 Pathophysiology of acute severe asthma ......................................................... 66
3.2.2 Oxygen therapy in acute severe asthma ........................................................... 68
3.3 Pneumonia............................................................................................................... 83
3.4 Summary ................................................................................................................. 86
Chapter 4: A randomised controlled trial of high concentration versus titrated
oxygen in acute asthma-methods ................................................................................... 88
4.1 Outline of the study ................................................................................................. 88
iv
4.2 Study objective and hypothesis ............................................................................... 89
4.3 Study participants.................................................................................................... 90
4.4 Randomisation ........................................................................................................ 91
4.5 Interventions ........................................................................................................... 91
4.6 Clinical measurements ............................................................................................ 93
4.6.1 Transcutaneous partial pressure of carbon dioxide (PtCO ) ............................ 93
2
4.6.2 Heart rate and oxygen saturation ..................................................................... 93
4.6.3 Spirometry........................................................................................................ 94
4.7 Study protocol ......................................................................................................... 94
4.8 Asthma treatment protocol ...................................................................................... 95
4.9 Outcome measures and statistical analysis ............................................................. 96
4.10 Sample size ........................................................................................................... 96
4.11 Ethical approval and trial registration ................................................................... 97
4.12 Study organisation ................................................................................................ 99
4.13 Data management.................................................................................................. 99
Chapter 5: A randomised controlled trial of high concentration versus titrated
oxygen in pneumonia-methods .................................................................................... 100
5.1 Outline of the study ............................................................................................... 100
5.2 Study objective and hypothesis ............................................................................. 100
5.3 Study participants.................................................................................................. 101
v
5.4 Randomisation ...................................................................................................... 102
5.5 Interventions ......................................................................................................... 102
5.6 Clinical measurements .......................................................................................... 104
5.6.1 Transcutaneous partial pressure of carbon dioxide (PtCO ) .......................... 104
2
5.6.2 Heart rate and oxygen saturation ................................................................... 104
5.6.3 CRB-65 score ................................................................................................. 104
5.6.4 Chest x-ray ..................................................................................................... 105
5.7 Study protocol ....................................................................................................... 105
5.8 Pneumonia treatment protocol .............................................................................. 106
5.9 Outcome measures and statistical analysis ........................................................... 107
5.10 Sample size ......................................................................................................... 107
5.11 Ethical approval and trial registration ................................................................. 108
5.12 Study organisation .............................................................................................. 108
5.13 Data management................................................................................................ 109
Chapter 6: A study of the physiological response to oxygen in chronic asthma -
methods .......................................................................................................................... 110
6.1 Outline of the study ............................................................................................... 110
6.2 Aims and objectives .............................................................................................. 111
6.3 Study participants.................................................................................................. 112
6.4 Study protocol ....................................................................................................... 113
vi
6.5 Study procedures ................................................................................................... 116
6.5.1 Transcutaneous partial pressure of carbon dioxide (PtCO ) .......................... 116
2
6.5.2 Heart rate and oxygen saturation ................................................................... 117
6.5.3 Spirometry...................................................................................................... 117
6.5.4 Mixed expired CO ........................................................................................ 117
2
6.5.5 Minute ventilation and respiratory rate .......................................................... 117
6.6 Outcome measures ................................................................................................ 118
6.7 Sample size ........................................................................................................... 118
6.8 Ethical approval and trial registration ................................................................... 118
6.9 Data management.................................................................................................. 119
Chapter 7: Validation of methods ............................................................................... 120
7.1 A validation study on the accuracy of transcutaneous carbon dioxide recordings 121
7.1.1 Introduction .................................................................................................... 121
7.1.2 Method ........................................................................................................... 122
7.1.3 Results ............................................................................................................ 123
7.1.4 Conclusion ..................................................................................................... 126
7.2 A repeatability study of the measurement of PtCO , minute ventilation, V /V and
2 D T
FEV1 ........................................................................................................................... 126
7.2.1 Method ........................................................................................................... 126
7.2.2 Statistical analysis .......................................................................................... 126
7.2.3 Results ............................................................................................................ 127
vii
7.2.4 Conclusion ..................................................................................................... 132
Chapter 8: Results......................................................................................................... 133
8.1 High concentration versus titrated oxygen in acute severe asthma ...................... 133
8.1.1 Subjects .......................................................................................................... 133
8.1.2 Changes in PtCO .......................................................................................... 136
2
8.1.3 Clinical variables ........................................................................................... 140
8.2 High concentration versus titrated oxygen in acute pneumonia ........................... 141
8.2.1 Subjects .......................................................................................................... 141
8.2.2 Changes in PtCO .......................................................................................... 145
2
8.2.3 Clinical variables ........................................................................................... 149
8.3 The physiological response to oxygen in chronic asthma .................................... 150
8.3.1 Subjects .......................................................................................................... 150
8.3.2 Changes in PtCO .......................................................................................... 151
2
8.3.3 Changes in MV, V /V , FEV1 and respiratory rate ...................................... 152
D T
Chapter 9: Discussion ................................................................................................... 155
9.1 Introduction ........................................................................................................... 155
9.2 Randomised controlled trials of high concentration versus titrated oxygen in acute
asthma and pneumonia ................................................................................................ 155
9.2.1 Key findings ................................................................................................... 155
9.2.2 Comparison with previous studies ................................................................. 159
9.2.3 Methodological issues .................................................................................... 161
viii
9.2.4 Interpretation and mechanisms ...................................................................... 169
9.3 A study of the physiological response to oxygen in chronic asthma .................... 172
9.3.1 Key findings ................................................................................................... 172
9.3.2 Comparison with previous studies ................................................................. 173
9.3.3 Methodological issues .................................................................................... 173
Chapter 10: Summary and conclusions ...................................................................... 177
References ...................................................................................................................... 183
Appendices ..................................................................................................................... 195
Appendix 1: Central Regional Ethics Committee approval for randomised controlled
trials of oxygen in acute asthma and pneumonia ........................................................ 195
Appendix 2: Central Regional Ethics Committee approval for a study of oxygen in
chronic stable asthma .................................................................................................. 195
Appendix 3: Information sheet, long consent form, and short consent form for
randomised controlled trials of oxygen in acute asthma and pneumonia ................... 195
Appendix 4: Information sheet and consent form for study of oxygen in chronic stable
asthma ......................................................................................................................... 195
ix
List of Figures
Figure 2.1: Haldane’s oxygen apparatus (Haldane, 1917) ................................................ 20
Figure 2.2: The oxy-haemoglobin dissociation curve....................................................... 26
Figure 2.3: The three compartment model showing an ideal lung unit (A) where
ventilation and perfusion are equally matched, Dead Space (I) with no perfusion,
and Shunt (V) with no ventilation. (Roca & Wagner, 1994) .................................... 29
Figure 3.1: Mechanisms of airflow limitation in COPD (Barnes, 2000) .......................... 37
Figure 3.2: Pulmonary hyperinflation in COPD (Sutherland & Cherniack, 2004) .......... 39
Figure 3.3: The Multiple Inert Gas Elimination Technique. Six inert gases are infused
intravenously while samples of arterial blood (a) mixed venous blood (v) and
mixed expired gases (E) are obtained. (Roca & Wagner, 1994) ............................... 42
Figure 3.4: Example of a MIGET graph from a normal individual breathing room air.
(Roca & Wagner, 1994) ............................................................................................ 42
• •
Figure 3.5: V /Q distribution in a patient with COPD. Note the bimodal appearance of
ventilation compared to perfusion due to areas of the lung with significantly
• •
elevated V /Q ratios (Agusti & Barbera, 1994). ...................................................... 43
Figure 3.6: Data showing no relationship between changes in minute ventilation and
P CO after oxygen at 5L/min for 30 minutes (Aubier, Murciano, Fournier et al.,
a 2
1980) ......................................................................................................................... 58
Figure 3.7: Change in gas exchange after three hours of oxygen administration in
eight presentations of acute severe childhood asthma (H. Simpson et al., 1968). .... 75
• •
Figure 3.8: V /Q distributions before and after 100% oxygen in two subjects with
• •
mild (top) and severe (bottom) baseline V /Q abnormalities (Corte & Young,
1985). ........................................................................................................................ 77
Figure 3.9: Changes in gas exchange before and during 100% oxygen therapy in
asthmatics with hypercapnia at baseline (Chien et al., 2000). .................................. 80
Figure 3.10: P CO before and after 20 minutes of oxygen therapy in the 28% and
a 2
100% oxygen groups (G. J. Rodrigo et al., 2003). .................................................... 82
x
Figure 3.11: Relationship between initial PEFR and P CO in the 100% group (G. J.
a 2
Rodrigo et al., 2003) ................................................................................................. 82
Figure 3.12: V/Q distribution of a mechanically ventilated pneumonia patient (Gea et
al., 1991). .................................................................................................................. 85
Figure 7.1 A Bland-Altman plot of the difference between the P CO and PtCO ,
a 2 2
against the average of P CO and PtCO (mmHg). Horizontal lines indicate plus
a 2 2
or minus 2 standard deviations of the differences. ................................................. 125
Figure 7.2: Bland-Altman plot of the difference between PtCO (mmHg) at visits one
2
and two against the mean value of the two visits. Horizontal lines indicate plus
or minus 2 standard deviations of the differences. ................................................. 128
Figure 7.3: Bland-Altman plot of the difference between MV(L/min) at visits one and

two against the mean value of the visits. Horizontal lines indicate plus or minus
2 standard deviations of the differences .................................................................. 129
Figure 7.4: Bland-Altman plot of the difference between FEV1(L) at visits one and

two against the mean value of the visits. Horizontal lines indicate plus or minus
2 standard deviations of the differences .................................................................. 130
Figure 7.5: Bland-Altman plot of the difference between V /V at visits one and two
D T
against the mean value of the visits. Horizontal lines indicate plus or minus 2
standard deviations of the differences ..................................................................... 131
Figure 8.1: Flow of asthma patients through the study. .................................................. 134
Figure 8.2: PtCO levels in asthma patients at baseline and after 60 minutes in the
2
high concentration (o) and titrated (●) oxygen groups. .......................................... 137
Figure 8.3: Flow of pneumonia patients through the study. ........................................... 142
Figure 8.4: PtCO levels in pneumonia patients at baseline and after 60 minutes in the
2
high concentration (o) and titrated (●) oxygen groups. .......................................... 145
Figure 8.5: PtCO versus time in patients with asthma (short dash line), COPD (long
2
dash line) and normal controls (solid line). Data points are mean plus or minus
one standard deviation. ........................................................................................... 152
Figure 9.1: The display of a TOSCA 500 transcutaneous carbon dioxide monitor. ....... 165