Table of Contents
TABLE OF CONTENTS…………………………………………………………………………………………………II
ABSTRACT……………………………………………………………………………………………………………………V
DECLARATION……………………………………………………………………………………………………….. VIII
ACKNOWLEDGEMENTS……………………………………………………………………………………………IX
PRESENTATIONS ARISING FROM THIS THESIS ……………………………………………………. XI
INVITED LECTURES ………………………………………………………………………………………………………. XI
PLATFORM PRESENTATIONS…………………………………………………………………………………………… XI
POSTER PRESENTATIONS……………………………………………………………………………………………… XIII
PUBLICATIONS ARISING FROM THIS THESIS…………………………………………………….. XVI
ABSTRACTS……………………………………………………………………………………………………………….. XVI
PAPERS……………………………………………………………………………………………………………………. XVIII
PAPERS SUBMITTED FOR PUBLICATION……………………………………………………………………………. XX
EDITORIALS BY PEERS ON PUBLICATIONS ARISING FROM THIS THESIS ………………………………….. XX
1. INTRODUCTION………………………………………………………………………………………………………..1
1.1 ANATOMY AND PHYSIOLOGY OF BODY FLUIDS IN HEALTH AND DISEASE…………………………….3
1.1.1 Body water compartments and internal fluid balance …………………………………………………………3
1.1.2 Content and concentrations…………………………………………………………………………………………….7
1.1.3 Fluid balance fluxes: Intake and turnover…………………………………………………………………………8
1.2 FLUID AND ELECTROLYTE BALANCE: EFFECTS OF STARVATION AND INJURY …………………….13
1.2.1 Effects on external balance …………………………………………………………………………………………..14
1.2.2 Effects on internal balance……………………………………………………………………………………………19
1.2.3 Clinical relevance ……………………………………………………………………………………………………….22
1.3 FLUID AND ELECTROLYTE PRESCRIPTIONS: TRAINING AND PRACTICE………………………………28
1.4 CONSEQUENCES OF SALT AND WATER EXCESS ……………………………………………………………..30
1.5 FLUID BALANCE AND GASTROINTESTINAL FUNCTION…………………………………………………….34
1.6 HYPOALBUMINAEMIA: CAUSES AND TREATMENT …………………………………………………………40
1.6.1 Inflammation — albumin distribution ……………………………………………………………………………43
1.6.2 Dilution……………………………………………………………………………………………………………………..45
1.6.3 Post-acute plasma hypovolaemia …………………………………………………………………………………..47
1.6.4 Metabolic …………………………………………………………………………………………………………………..49
1.6.5 Other considerations……………………………………………………………………………………………………50
1.6.6 Conclusions………………………………………………………………………………………………………………..50
1.7 THE EFFECT OF CRYSTALLOID INFUSIONS IN NORMAL SUBJECTS ……………………………………..51
2. METHODS ………………………………………………………………………………………………………………..55
2.1 WEIGHT AND HEIGHT ……………………………………………………………………………………………….56
2.2 BIOELECTRICAL IMPEDANCE ANALYSIS………………………………………………………………………56
2.3 GASTRIC EMPTYING TIME ………………………………………………………………………………………….57
2.4 HAEMATOLOGICAL PARAMETERS……………………………………………………………………………….57
2.5 BIOCHEMICAL PARAMETERS………………………………………………………………………………………58
2.6 ETHICS AND CONSENT ………………………………………………………………………………………………58
2.7 STATISTICAL ANALYSIS…………………………………………………………………………………………….59
CLINICAL STUDIES…………………………………………………………………………………………………….60
3. CHANGES IN WEIGHT, FLUID BALANCE AND SERUM ALBUMIN IN PATIENTS
REFERRED FOR NUTRITIONAL SUPPORT ………………………………………………………………61
3.1 INTRODUCTION………………………………………………………………………………………………………..62
3.2 METHODS……………………………………………………………………………………………………………….63
ii
3.3 RESULTS…………………………………………………………………………………………………………………64
3.4 DISCUSSION…………………………………………………………………………………………………………….70
4. THE NATURAL HISTORY OF CHANGES IN TRANSCAPILLARY ESCAPE RATE
OF ALBUMIN IN PATIENTS UNDERGOING MAJOR ABDOMINAL SURGERY……….75
4.1 INTRODUCTION………………………………………………………………………………………………………..76
4.2 METHODS……………………………………………………………………………………………………………….77
4.3 RESULTS…………………………………………………………………………………………………………………78
4.4 DISCUSSION…………………………………………………………………………………………………………….78
5. REPRODUCIBILITY AND NORMAL RANGES FOR GASTRIC EMPTYING IN
VOLUNTEERS USING A TEST MEAL DESIGNED FOR POSTOPERATIVE PATIENTS
………………………………………………………………………………………………………………………………………82
5.1 INTRODUCTION………………………………………………………………………………………………………..83
5.2 METHODS……………………………………………………………………………………………………………….83
5.3 RESULTS…………………………………………………………………………………………………………………86
5.4 DISCUSSION…………………………………………………………………………………………………………….90
6. EFFECT OF SALT AND WATER BALANCE ON GASTROINTESTINAL FUNCTION
AND OUTCOME AFTER ABDOMINAL SURGERY: A PROSPECTIVE RANDOMISED
CONTROLLED STUDY………………………………………………………………………………………………..92
6.1 INTRODUCTION………………………………………………………………………………………………………..93
6.2 METHODS……………………………………………………………………………………………………………….94
6.2.1 Study Design…………………………………………………………………………………………………….94
6.2.2 Selection Criteria ……………………………………………………………………………………………..94
6.2.3 Randomisation, study groups and interventions…………………………………………………….95
6.2.4 Clinical Management ………………………………………………………………………………………..96
6.2.5 End points………………………………………………………………………………………………………..96
6.2.6 Sample size and power calculation ……………………………………………………………………..97
6.2.7 Monitoring……………………………………………………………………………………………………….97
6.2.8 Gastric emptying ………………………………………………………………………………………………98
6.2.9 Assay of gastrointestinal hormones……………………………………………………………………..99
6.2.10 Statistical Analysis ………………………………………………………………………………………….99
6.3 RESULTS…………………………………………………………………………………………………………………99
6.4 DISCUSSION…………………………………………………………………………………………………………..108
SURVEYS ……………………………………………………………………………………………………………………113
7. PROBLEMS WITH SOLUTIONS: DROWNING IN THE BRINE OF AN
INADEQUATE KNOWLEDGE BASE …………………………………………………………………………114
7.1 INTRODUCTION………………………………………………………………………………………………………115
7.2 METHODS……………………………………………………………………………………………………………..115
7.3 RESULTS……………………………………………………………………………………………………………….118
7.4 DISCUSSION…………………………………………………………………………………………………………..126
8. PERIOPERATIVE FLUID AND ELECTROLYTE MANAGEMENT: A SURVEY OF
CONSULTANT SURGEONS IN THE UNITED KINGDOM…………………………………………129
8.1 INTRODUCTION………………………………………………………………………………………………………130
8.2 METHODS……………………………………………………………………………………………………………..130
8.3 RESULTS……………………………………………………………………………………………………………….131
8.4 DISCUSSION…………………………………………………………………………………………………………..137
STUDIES IN NORMAL VOLUNTEERS………………………………………………………………………146
9. BODY WATER COMPARTMENT MEASUREMENTS: A COMPARISON OF
BIOELECTRICAL IMPEDANCE ANALYSIS WITH TRITIUM AND SODIUM
BROMIDE DILUTION TECHNIQUES………………………………………………………………………..147
9.1 INTRODUCTION………………………………………………………………………………………………………148
iii
9.2 METHODS……………………………………………………………………………………………………………..149
9.2.1 Tritium Analysis (Vaughan and Boilin 1961)………………………………………………………150
9.2.2 NaBr Analysis…………………………………………………………………………………………………150
9.2.3 Statistical Analysis ………………………………………………………………………………………….152
9.3 RESULTS……………………………………………………………………………………………………………….152
9.4 DISCUSSION…………………………………………………………………………………………………………..156
10. THE DILUTION AND REDISTRIBUTION EFFECTS OF RAPID 2 LITRE
INFUSIONS OF 0.9% (W/V) SALINE AND 5% (W/V) DEXTROSE ON
HAEMATOLOGICAL PARAMETERS, SERUM BIOCHEMISTRY AND
BIOELECTRICAL IMPEDANCE ANALYSIS IN NORMAL SUBJECTS: A DOUBLE
BLIND CROSSOVER STUDY……………………………………………………………………………………..158
10.1 INTRODUCTION…………………………………………………………………………………………………….159
10.2 METHODS……………………………………………………………………………………………………………160
10.3 RESULTS……………………………………………………………………………………………………………..162
10.4 DISCUSSION…………………………………………………………………………………………………………166
11. THE EFFECT OF VOLUME LOADING WITH 1 LITRE INTRAVENOUS
INFUSIONS OF 0.9% (W/V) SALINE AND 5% (W/V) DEXTROSE ON THE RENIN
ANGIOTENSIN ALDOSTERONE SYSTEM AND VOLUME CONTROLLING
HORMONES: A RANDOMISED, DOUBLE BLIND, CROSSOVER STUDY………………..172
11.1 INTRODUCTION…………………………………………………………………………………………………….173
11.2 METHODS……………………………………………………………………………………………………………174
11.2.1 Study design and setting …………………………………………………………………………………174
11.2.2 Subjects………………………………………………………………………………………………………..174
11.2.3 Baseline assessment, blood and urine sampling…………………………………………………174
11.2.4 Infusion and sampling protocol……………………………………………………………………….175
11.2.5 Hormonal analysis ………………………………………………………………………………………..176
11.2.6 Statistical analysis…………………………………………………………………………………………178
11.3 RESULTS……………………………………………………………………………………………………………..178
11.4 DISCUSSION…………………………………………………………………………………………………………185
12. (AB)NORMAL SALINE AND PHYSIOLOGICAL HARTMANN’S SOLUTION: A
RANDOMISED DOUBLE BLIND CROSSOVER STUDY…………………………………………….193
12.1 INTRODUCTION…………………………………………………………………………………………………….194
12.2 METHODS……………………………………………………………………………………………………………195
12.3 RESULTS……………………………………………………………………………………………………………..197
12.4 DISCUSSION…………………………………………………………………………………………………………200
13. THE EFFECT OF AN ORAL GLUCOSE LOAD ON SODIUM AND WATER
EXCRETION AFTER RAPID INTRAVENOUS INFUSION OF 0.9% (W/V) SALINE….207
13.1 INTRODUCTION…………………………………………………………………………………………………….208
13.2 METHODS……………………………………………………………………………………………………………208
13.3 RESULTS……………………………………………………………………………………………………………..210
13.4 DISCUSSION…………………………………………………………………………………………………………212
CONCLUSIONS…………………………………………………………………………………………………………..217
FURTHER STUDIES……………………………………………………………………………………………………….222
LIST OF ABBREVIATIONS………………………………………………………………………………………..224
REFERENCES…………………………………………………………………………………………………………….227