Textbook of Ventilation, Fluids, Electrolytes and Blood Gases Mohan Gurjar
Page numbers followed by b refer to box, f refer to figure, fc refer to flowchart, and t refer to table.
Abdomino-thoracic index, calculation of 259f
Abscess drainage 390
Acetate 244
abnormalities 350, 351
component of 331
disorder 330, 350
metabolic 329
primary 329
disturbance 349, 352, 353, 355, 358, 361
homeostasis 325
status 351
Acidemia 336
Acidic drugs 246
Acidic liquid 369
Acidosis 294, 348, 360
acute respiratory 41, 326, 331
chronic respiratory 326, 331, 344, 346
compensation, chronic respiratory 327f
hypercapnic 343, 344
state of 350
Acinetobacter 190
Acrodermatitis enteropathica 384
Activated clotting time 205
Activated partial thromboplastin time 205
Acute coronary syndrome 335, 389
Acute hypercapnic respiratory failure 35
Acute hyponatremia 282, 282b
causes of 279fc
Acute lung injury, transfusion-related 388, 392, 393
Acute respiratory distress syndrome 3, 29, 49, 74, 88, 121, 138, 151, 197, 216, 220, 224, 269, 272, 376, 389
pathophysiology of 85
severe 198
Adenine 387
monophosphate 307
monophosphate 44
triphosphate 307, 374, 389
Adrenaline 402
Adult respiratory distress syndrome 389
Advanced cardiac life support 24, 32
Aerosolized therapy 192
Air 66, 71
embolism 218
devices 21
nebulizers 22
mask 19, 22f
humidification, degree of 181
trapping 82
exhale causing 108
Airway 87
access, type of 184
anatomy 181
burns, context of 4
mechanisms 182
system 229f
collapse, volume related 11
chronic 397
severe 403
management equipment 227
obstruction of 61
occlusion pressure 142, 166
pressure 137, 152, 220
release ventilation 121123
protection of 61
resistance 144
Albumin 251, 350, 367
concentration of 330
low 43
parathyroid hormone 309
Albuterol sulfate 183
Alcohol 315
abuse 307
dehydrogenase 334
Alkalemia 338
Alkaline suspension 369
Alkalosis 332, 346, 356, 360
acute respiratory 328, 328f, 331
chronic respiratory 328, 331
diuretic-induced 338
state of 350
Allen test 348
Allergic reactions 394
Alveolar arterial oxygen gradient 29, 39
Alveolar capillary
boundary 119
membrane 28
perfusion 10
Alveolar dead space 10
Alveolar epithelial cells 8, 14
Alveolar gas equation 28, 29
Alveolar oxygen
content 30
tension ratio 30
Alveolar plateau phase 119f
Alveolar pressure 82, 151
Alveolar recruitment maneuvers 105
Alveolar ventilation 10, 36, 342
inadequate 342
Alveoli, functional cellular anatomy of 9f
American Thoracic Society 85, 172, 177
Amino acid 373, 375
Aminoglycosides 284
Ammonium chloride 340
Amphotericin B 190, 284
Amylopectin 248
Anaerobic metabolism 245
Anaphylactic reactions 394
Anaphylaxis 253
Anemia 43, 388
epidural 241
ventilators 71
Angiotensin converting enzyme 3, 240
inhibitors 294
Angiotensin receptor blockers 294
Anion gap
approach 351
metabolic acidosis, normal 330
normal 335
Antibiotics 190, 308
Anticholinergics 254
bronchodilator 41
Anticonvulsants 308
Antidiuretic hormone 239, 276, 278
level 277fc
Antidotes 41
Antigen presenting cells 3
Antineutrophil antibodies 393
Antioxidant 369
supplementation 369
Anxiety 346
Apixaban 392
Apnea 397
hypopnea index 42
test 397
Arginine 369, 373375
deficiency 376
physiology 375
source 375
toxicity 376
vasopressin 255, 275
Arrhythmias 291, 299, 399
Arterial blood
care and transport of 348
gas 35, 48, 207, 254, 311, 346, 348, 355, 356t359t, 360, 360t
analysis 32, 39, 254
interpretation, basics of 348
values 311t
pressure 251
samples 348
Arterial cannulation 215
Arterial carbon dioxide
partial pressure of 36
tension 176
Arterial gas embolism 25
Arterial oxygen
content 27, 30
saturation 27, 176
measurement of 115
tension 42, 176
Arterial puncture 349
Arteriovenous pumpless system 214
Artificial airway 181, 183
Artificial colloid 247
Aspartate aminotransferase 312
Aspiration 371
pneumonia 85
protection from 6
risk of 226, 367
Aspirin 246
Assist control ventilation 69, 147
Asthma 50, 334, 342, 346
comprise of 77
severe 78, 79t
treat 289
index 107
types of 108
Ataxia 315
Atelectasis 29, 33
Atelectrauma, prevention of 155
Atmospheric pressure 151
Atrial fibrillation 333
Atrial natriuretic peptide 241
Atrial pressure, right 129f
Autoimmune polyglandular syndrome 298
Auto-positive end-expiratory pressure 78, 108
Aztreonam 190
Bacteremia, gram-negative 309
Bacteria, gram-negative 190
Bacterial colonization 8
Bacterium leuconostoc mesenteroides 248
Bag mask
device 24, 24f, 31
ventilation 19, 33
Balanced colloid solution 269
Balanced salt solutions 245
Barbiturate 246
Barometric pressure 30, 39
Barotrauma 109, 220
predisposes to 85
Bartter's syndrome 290, 315, 316, 338
Basal pressure 91
Basic acid-base physiology 349
Basolateral membrane 283
Baydur test 141
Beer's law 114
Beta-adrenergic blockers 293
Bicarbonate 246
therapy 301
Bifidobacteria 368
Bilevel positive airway pressure 35, 59, 60, 69
Bilirubin 115
Bioelectrical impedance analysis 238, 261
Bio-med devices 73
Biotrauma 9
Bisphosphonates 304, 305t
Bivaluridin 205
Bleeding 254
tendency, history of 391
flow 122, 323
analysis 333
partial pressure of 117
glucose 237
loss, exceptional anemia from 25
pressure 53, 54, 176, 211, 240, 348, 400
products, transfusion of 387
transfusion 388
reaction 393
urea 237
nitrogen 35, 276
volume index 261
Body fluid 238
compartments 235
composition of 236
volume of 237t
distribution of 236f
homeostasis 235, 266
spaces, measurement of 237
Body mass index 35, 207, 216
Bone resorption, prevent 304
Boston rules 329
Bowman's glands 3
Boyle's law 24
Bradycardia 319
death 396, 397
diagnosis of 396fc, 396t, 397
effects of 399
pathophysiology of 400
dysfunction 388
injury 271
natriuretic peptide 241, 254
death 400
reflexes 397
absent 397
Breath stacking 78
Breathing 107
cycle 55
pattern of 21
trial failure
signs of spontaneous 176t
symptoms of spontaneous 176t
work of 14, 48, 53
Brewer's yeast 380
Broad-spectrum antibiotics 368
Bronchial asthma 77
Bronchial smooth muscle, role of 8
Bronchioles 8
Bronchoconstriction 182
Bronchodilatation 105
receptors 181
role of 41
therapy, effect of 104
Bronchopleural fistula 83, 94
etiologies of 83t
harmful effects of 84t
management of 84
preventive strategies for 84
Bronchoscopy, fiberoptic 83
Bronchospasm 70, 78, 100, 184
Bubble reduction 24
Bulbar dysfunction 43
Calcimimetics 305
Calcitonin 296, 297
Calcium 244, 296
chloride 301
functions of 296b
gluconate 295, 301
metabolism 297f
sensing receptor 315
sizes 203t
variety of 203t
Capillary blood flow 3
Capillary endothelium destruction 25
Capillary leak index 254
Capnograph 118
Carbamazepine 239, 370
Carbohydrates, oxidation of 235
Carbon dioxide 35, 47, 71, 119, 213, 217
clearance 222
concentrations 114
measurement 117
monitoring 40
partial pressure of 209, 342
tension in blood, measurement of 117
Carbon monoxide
intoxication 334
poisoning 18
severe 25
Carbonic acid 350
Carboxyhemoglobin 117
Cardiac chambers, volume of 131
Cardiac disease 387
active 394
Cardiac dysfunction 144
Cardiac index 258
Cardiac output 18, 27, 115, 198
syndrome, low 197
total 30
Cardiac surgery, protective ventilation in 125
Cardiac tamponade 32, 253
Cardio-abdominal-renal syndrome 261
Cardiogenic pulmonary edema, management of 135
Cardiovascular disease 388
Cardiovascular disorders 380
Cardiovascular system 130, 177, 240, 299, 319
Carpopedal spasm 300
Cartilage, long teardrop-shaped 5
Catabolic stress 365
Caudal ventrolateral medulla 239
Cavities, abdominal 161
Cefotaxime 190
Ceftazidime 190
Cell structures, part of 307
acidosis 334
defense 373
dysfunction 309
metabolism 307
Central nervous system 37, 177, 199, 206, 278
disorders 225
dysfunction 199
toxicity 25
Central respiratory depression 31
Central venous pressure 132, 251, 258, 268, 401
attack 335
edema 245, 271
ischemia 246
salt-wasting syndrome 271
tissue oxygenation 388
Cerebrospinal fluid 37
Cervical spine injuries, high 31
Cetuximab 315, 317
deformations 50
physiotherapy 92, 105
radiograph 40
trauma 83
tube 366
management 84
occlusion, intermittent inspiratory 84
placement 83
wall 12, 78
diagnosis of 343
Chloride 244
levels of 269
responsive metabolic alkalosis 338
Chloroquine toxicity 40
Cholecalciferol 379
Cholera, physiology of 243
Chromium 382
Chronic obstructive pulmonary disease 13, 36, 49, 82, 92, 164, 181, 190, 216, 217, 225, 289, 338, 344
Chvostek's sign 300
Circulatory system, medications performance of 48
Cisplatin 284
Citrate phosphate dextrose 387
Clark electrode 116
Claustrophobia 25
Clofibrate 239
Clostridial myonecrosis 25
Colitis 319
Colloid 247
oncotic pressure 237, 254
osmotic pressure 268f
solutions 401
Colored nail varnish 115
Coma 397
Complete blood count 33, 40, 205
Compressed gas storage system 5
decreased level of 4
depressed level of 77, 239
Continuous positive airway pressure 49, 91, 121, 174, 224
Conventional ventilatory support 196
Core body temperature 4
Cormack-Lehane descriptive system 5
Coronary artery bypass grafting 376
Cortical collecting tubule 294
Corticosteroids 284
ineffective 61
reflex, trachea in 3
strength 144
C-reactive protein 254
Creatine phosphokinase 40
Cricoid cartilage 5
Critical care myopathy 173
Critical illness polymyoneuropathy 162
Crystalloid 243, 249, 271
solutions 243, 271
Cumulative fluid balance 253
Cushing's syndrome 290
Cyanosis 179
Cycled air, humidity of 181
Cystic fibrosis 182
Cytokines 86
Cytotoxic drugs 308
Dabigatran 392
Decompression sickness 25
Dehydration 253
Demeclocycline 284
Dental barotrauma and pain 25
Dephlogisticated air 17
Depressed mental status 176, 179
Dextran 243, 248
Dextransucrase 248
Dextrose 294, 387
containing fluid 245, 246
Diabetes insipidus 240, 283, 285, 402
Diabetes mellitus 284
acute complication of 335
Diaphoresis 179
Diaphragm 67, 162
activity, monitor 166
anatomy 161
dysfunction 162
development of 163fc
diagnostic of 166
electric activity 165
electrical activity of 73, 148
excursion of 147
function 161
inactivity 164
pressure generation, ratio of 165
protective ventilation concepts 166
thickness 147
ultrasound 147
Diaphragmatic dysfunction, ventilator-induced 147, 161, 163, 167
Diarrhea 253, 254, 271, 384
chronic 308, 315
Diastolic function 256
Diethylene glycol 334
Diodes, light-emitting 114
Dipalmitoylphosphatidylcholine 9
Disinfectant solution 227
Disinfection techniques 229
Distal nephron function, abnormal 291
Disulfiram 247
Dizziness 346
Dobutamine 289
Docosahexaenoic acid 376
Domiciliary ventilators 227
Dorsal chest 122
Double gap acidosis 334
Driving pressure 95, 141, 156
dose 183
formulation 183
interactions 369
properties of 181
Dry cold gas 5
Dry powder inhalers 184
Duchenne muscular dystrophy 37
Duodenum 307
Dynamic hyperinflation 47, 78, 85, 107
hemodynamic consequences of 79
Dynamic occlusion test 148
Dysplasia, bronchopulmonary 220
Dyspnea 39, 48
sudden onset of 83
Dyssynchrony 85
Echocardiography 208
Edema 241
cardiogenic pulmonary 49, 226
pulmonary 135fc
Edoxaban 392
Effective circulatory fluid volume 279, 280
Eicosapentaenoic acid 376
Eisenmenger's syndrome 30
Ejection fraction 251
Electrical impedance tomography 261
Electrocardiogram 35
Electroencephalogram 38
Electrolyte 255
abnormalities 317
balance 330
compartments of 235
disturbance 144, 357
management of 312
severe 173
Electromagnetic stimulation 147
Electromyography 40, 166
Emergency medical services 71, 73
End-diastolic volume 129, 257, 259
End-expiratory collapse 124
End-expiratory lung volume 78, 152
End-expiratory occlusion 258
button 138
technique 80
test 135, 261
End-inspiratory muscle pressure 142
Endobronchial intubation 32
Endoluminal bronchial secretions 182
Endothelial cells, cytoskeleton of 9
Endothelial glycocalyx 252
Endothelial nitric oxide production 122
Endotracheal intubation 6
Endotracheal tube 94, 157, 184, 186
End-tidal carbon dioxide analyzer 118
Enteral nutrition 366, 370
Epidermal growth factor 314, 315
Epiglottic cartilage 5
Epiglottis 4
Epilepsy 315
Epithelial cells, cytoskeleton of 9
Eplerenone 294
Esophageal Doppler monitoring 257
Esophageal manometry 124
Esophageal pressure 80, 141, 146, 148, 157, 161
Esophageal region, fresh fixations in 61
Esophagus 145
Estimated glomerular filtration rate 199
Ethanol 284
Ethylene 334
Ethylenediaminetetraacetic acid 293, 298
European Respiratory Society 172, 177
Euvolemia 253, 272
Expiratory flow
limitation 82, 99f
consequences of 82
obstruction, causes of 84
until downstream water 82
Expiratory muscles, activation of 82, 112f
Expiratory positive airway pressure 52, 57
Expiratory sensitivity 111f
Extracellular fluid 235, 236, 238, 275, 307
composition and volume, regulation of 238, 240
volume 240fc
regulation of 240
Extracellular space 243
Extracellular water 262
Extracorporeal blood flow rate 215
Extracorporeal carbon dioxide removal 196, 200, 213
Extracorporeal cardiopulmonary resuscitation 203
Extracorporeal circuit configuration 214f
Extracorporeal Life Support 199
Organization 196, 198
Extracorporeal membrane
carbon dioxide removal 213
oxygenation 43, 87, 88, 196, 197, 197t, 197f, 198, 200, 201, 206, 209, 210
Extracorporeal membrane oxygenation
cannulation 207, 211
contraindication for 197, 198
management of 202
Extracorporeal therapy 215t
Extravascular lung water 258, 259
index 261
Extubation failure, risk factors for 43b
Face mask 51, 52
simple 19, 20f
Face tent aerosol mask 23f
edema 87
hair, thick 52
sensation 397
skeleton, trauma of 61
Fanconi's syndrome 308
Fast oxygen delivery 72
Fatal metabolic alkalosis 350
Fatty acids 373, 376
essential 368
Febrile nonhemolytic reaction 392, 394
Femoral artery, left 204f
Femoral vein cannula, simultaneous left 201f
Fistula 84
arteriovenous 302
Fluid 253
adverse effects of 268
and Catheter Treatment Trial 269
and electrolytes 233
balance 32, 252, 254
bolus therapy 269
choice of 285t
classification of 243
disturbance 357
homogeneous 243
interstitial 236, 236f, 237
loss 253
during surgery 241
osmotic properties of 243
responsiveness 253, 258
predictor of 256
resuscitation, history of 266
therapy 266, 270, 401
goals of 266fc
maintenance 269
unresponsiveness 260f
Forced vital capacity 35
Fresh frozen plasma 204, 206, 389
indications 390
preparation 390
storage 390
Functional residual capacity 8, 11, 78, 94, 130, 152
concept of 78
Furosemide 294, 319
Galactosemia 308
Gamblegram 337f
exchange 144, 215
catheters 214, 215
pathophysiology of 197
mixture, volume of 21
partial pressure 349
supply 66
trapping 78
catheter 148
contents, aspiration of 366
mucosal pH measurement 120
pressure 146, 161
tonometer 120f
tubes 52
Gastrointestinal failure 375
Gastrointestinal tract 241, 296, 314
Gelatin 248
solutions, types of 248
Gilbert index 165
Gitelman's syndrome 290, 291, 315, 317
Global ejection fraction 258
Global end-diastolic volume index 258
Glomerular filtration rate 240
Glucocorticoids 305
Gluconate 244, 369, 373375
deficiency 375
high-dose 375
in ICU 375
physiology 374
source 374
supplementation 375
Glutathione depletion 334
Glycogen storage diseases 308
Graft versus host disease 394
Granulomatous diseases 302
Guillain-Barre syndrome 31, 37, 343
Haldane effect 36
Hans Rudolph half mask 51f
Harlequin syndrome 203, 204f
Hartmann's solution 245
Headaches, cluster 18
failure 32, 39, 254, 266, 289, 299
chronic 177
congestive 278, 279
decompensated chronic 197
function 396
lung interaction 128
clinical applications of 131
determinants of 128
rate 18, 54, 134, 258, 348
rhythm 134
and moisture exchanger 52, 184
exchange malfunctions 218
Hemiplegia 38
Hemodynamic monitoring 258
techniques 256
Hemodynamic support 202, 400
Hemoglobin 198, 350, 387
bound oxygen 27
concentration 18, 27, 115, 117
deoxygenated 117
oxygen dissociation curve 343
Hemolysis 218
Hemolytic transfusion reactions 394
Hemorrhage, intra-alveolar 25
Henderson-Hasselbalch equation 119, 351
Heparin, unfractionated 204206
Hepatocyte nuclear factor 315
Hepatorenal syndrome, development of 272
Hernia, congenital diaphgramatic 223
High anion gap metabolic acidosis 333
High expiratory flow rate 59
High frequency oscillatory ventilation 88, 121, 123, 220, 222
advantages of 222
disadvantages of 222
indications 220
initiation of 220
weaning from 222
High-flow devices 21
High-frequency oscillation ventilation 43
Home-based ventilation 178, 225, 226, 230
classification of 226t
disinfection of 229
Homeostasis 235
replacement therapy 402
role of 241
Human albumin 247
fluids 247
half-life of 247
Human immunodeficiency virus 298
Human leukocyte antigen 393
Human nasal hair differs 4
Human neutrophil antigens 393
Human serum albumin 272
Humidification 57
nose in 3
poor 8
Hungry bone syndrome 298, 315
Hydrochlorothiazide 315
Hydrogen ion 36
Hydrostatic pressure 122, 243
effect 241
Hydroxyapatite 296
Hydroxyethyl starch 244, 248, 249, 401
Hyoepiglottic ligament 5
Hyperbaric oxygen 24
therapy 19, 24, 24b
effect of 24f
physiologic effects of 24
side effects of 25, 25b
uses of 25b
Hyperbilirubinemia 311
Hypercalcemia 247, 296, 302, 304fc, 330
clinical effects 303
clinical presentation of 303t
etiology 302, 302b
evaluation 303
management 303
mild 302, 303
severe 303
Hypercalciuria 315
Hypercapnia 35, 40fc, 217
acute 37, 38
advantages of 38
chronic 38
common causes of 39fc
disadvantages of 38
effects of 37t, 343
evaluation of 39
impact of 43
management of 35
mechanism of 36
prognosis of 35
symptoms of 39
Hypercapnic respiratory failure 42, 47
differential diagnosis of 39
Hypercarbia, managing 222
Hyperglycemia 254, 371, 400
control 308
Hyperglycemic syndromes, severe 272
Hyperinflation, mechanism of 78
Hyperkalemia 247, 288, 291, 292f, 294, 295, 312
cause of 293
clinical effects 294
differential diagnosis of 292t
etiology 291
evaluation 294
management 294
mechanism 291
treatment of 294t, 295
Hyperlactatemia 245, 357
Hypermagnesemia 314, 318, 319, 319t, 330
clinical effects 319
etiology 318
evaluation 319
management of 319, 320
mechanism 318
Hypernatremia 254, 275, 283, 284fc, 285fc
causes of 283t
chronic 284
clinical features 283
drugs causing 284t
etiology 283
management of 286
Hyperoncotic albumin solutions 272
Hyperoxia 24
effects of 25
Hyperoxygenation 24
primary 302
tertiary 305
Hyperphosphatemia 307, 310, 311, 311t, 312
cause of 310
etiology 310
management 312
Hyperpnea 284
Hypertension 399
arterial 333
Hyperthermia, malignant 311
Hypertonic saline 282
Hypertonicity 294
Hypertriglyceridemia 371
Hyperventilation 118
physiological effects of 85
Hypervitaminosis 284
Hypervolemia 135, 253, 277
Hypervolemic hypernatremia, diagnosis of 285
Hypoalbuminemia 266
Hypocalcemia 37, 296298, 300fc, 301, 306, 312, 316
clinical presentation of 299t
etiology 298, 298b
evaluation 300
management 300
mechanism 298
mild 300
pearls in managing 301
severe 300
symptomatic 300, 312
treatment of 300, 301b
Hypocapnia 346
Hypochloremia 330
Hypoglycemia 25
Hypokalemia 37, 288290, 317
causes of 289, 290
clinical effects 290
development of 295
differential diagnosis of 290t
etiology 288
evaluation 290
management 291
mechanism 288
Hypomagnesemia 37, 310, 314, 315, 315t, 316, 317, 318fc
amplification loop of 316fc
causes of 315, 315b
familial 315
Hyponatremia 275277, 277fc, 278, 280, 281fc, 282b, 330
category of 277
causes of 280, 282, 282b
chronic 280, 281fc
diagnostic evaluation of 279fc
etiologies for 278
evaluation of 278
hypertonic 277
management of 282
pathogenesis of 277
pathophysiology of 278fc
rapidly corrected 282
therapy of 280
true 277
Hypoperfusion, treatment of 266
Hypophosphatemia 37, 307, 307t, 308310
clinical effects 309
drug-induced 308t
etiology 307
management 309
severe 309
severity of 309
treatment of 309
X-linked 308
Hypotension 83, 122, 310, 319
Hypothalamic disease 239
Hypothyroidism 40
Hypotonic solutions 271
Hypoventilation 30, 32
Hypovolemia 241, 251253, 255, 262, 277, 284
absence of 338
absolute 241
causes of 241t
clinical signs of 254b
consequences of 253
etiology of 253
hemodynamic parameters in 258b
laboratory biomarkers for 254b
signs of 256b
situations of 85
Hypoxemia 27, 32, 33, 35, 346
absence of 17
classification of 18t
differential diagnosis of 32fc
managing 221
mechanism of 29
mild 18
moderate 18
severe 18, 356
symptoms of 17
Hypoxia 18, 27, 346
types of 19, 19t
Hypoxic blood 10
Hypoxic pulmonary vasoconstriction 28
Immune system 383
Immunity, humoral 3
Immunoglobulin molecules 3
Immunonutrition 373
Impair diaphragm muscle function 162
Indocyanine green 115
Infection 144, 206
Inferior vena cava 134, 200, 256
Inferior vena collapsibility index 257f
Inflammation 37
Inspiratory air, humidification of 58
Inspiratory flow 84
rate 156, 183
Inspiratory muscle pressure index 142
Inspiratory muscle training 168
role of 168
Inspiratory oxygen fraction 176
Inspiratory positive airway pressure 52, 57
Inspiratory pressure 138, 142
generation 146
maximal 54, 174, 179
Inspired air, humidity of 4
Inspired oxygen, fraction of 18, 29, 35, 48, 69, 73, 153, 156, 186, 192, 197, 202
Insulin 294
deficiency 294
plus glucose 294, 295
Intellivent-adaptive support ventilation 73
Intensive care unit 5, 28, 40, 42, 66, 114, 144, 161, 172, 196, 207, 224, 238, 248, 251, 269, 288, 342, 355, 366, 373
Interleukin 8 156
Internal jugular vein 200
Intestinal disorders, primary 308
Intestinal malabsorption 308
Intra-abdominal pressure 122, 129, 252, 261
Intracellular fluid 236, 236f, 238, 275, 307
Intracellular water 261
Intracranial pressure 243
Intrapleural pressure, application of 84
Intrathoracic pressure 129
effect of 129, 130fc
hemodynamic effects in 129
Intravenous ferric carboxymaltose 389
Intravenous fluid 243, 269
Invasive mechanical ventilation, sedation in 43
Ipratropium bromide 41
Ischemia reperfusion injury 400
Ischemic central nervous system lesions 31
Isothermic saturation boundary 5
Isotonic bicarbonate solution 245, 247
Isotonic crystalloid 401
Isotope dilution techniques 262
Janus Kinase-signal transducer 166
Jaw thrust 4
Jejunostomy tube 369
Jejunum 307
Jet entrainment 22f
Jet nebulizer 185, 188
Jugular venous pressure 254, 400
Ketoacidosis, diabetic 272, 311
Kidney 206
disease 253
chronic 249, 295, 299, 302, 311, 333
dysfunction 255
failure 367
chronic 333
injury, acute 261, 269, 293, 295, 312, 357
Krebs cycle 334
Kussmaul's breathing 85
Kussmaul's sign 132
Kyphoscoliosis 40, 225
Lactobacillus 368
Lamina densa 9
Laryngeal nerve 6
Laryngeal sensory chemoreceptors 6
Laryngoscopy 5
Laryngospasm 6
Larynx 5
anatomy of 5, 6f
Leakage compensation 55, 56
Left vein cannulation 204f
Left ventricular
ejection 135
failure 359
outflow tract 256
Levodopa, level of 370
Levothyroxine administration 370
Life-threatening bleed, management of 392
Limb ischemia 204
Lipid metabolism, incomplete 325
Liquid consistency 369
Lithium 246, 284
disease 272, 368, 371, 391
acute 391
chronic 272
failure 272
chronic 367
function tests 33
Loop diuretics 284
Loop expresses airway resistance 91
Loop system flow, leakage in 104
Loops analysis 100
Low pressure region 151
Low serum osmolality 277
Low tidal volume
strategy 84
ventilation 86
Lowe's syndrome 308
Low-pressure receptors, mechanism of action of 239fc
Lumbar vertebrae 161
Lung 86
aeration 182
capacity, total 11
compliance 134
consolidation, effects of 13
disease, interstitial 40
elastic recoil 98
function 396
hyperinflated 257
acute 85, 334
prevention 41
ventilator-induced 86, 121, 124, 151, 172, 217, 402
parenchyma 12
compression of 122
one-lung ventilation 125
ventilation 43, 88
evaluation of 140
high potential of 140f
low potential of 140f
maneuvers 121, 125
maneuvers, advantages of 123t
maneuvers, disadvantages of 123t
methods 121b
regions, aeration of 181
stress and strain 141
surface area increase 157
transplant 218
volume 124
and capacities 11
at end-expiration 79
hemodynamic effects to changes in 130
zones of 10
Lymphatic system 241
Lymphoid tissue, gut-associated 365
Macronutrients 374
functions of 374t
Magnesium 244, 299
homeostasis 314
clinical effects 316
etiology 315
management 317
mechanism 315
Mainstem bronchi 183
Malate 244
Malnutrition 365
Manganese 382
Manitol 284
Mask 51, 54
designs 22
non-rebreather 19, 21, 21f
Mass median aerodynamic diameter 182
Massive transfusion 393
Maximum inspiratory flow 68
Maximum inspiratory pressure 144, 146, 165
McCune-Albright syndrome 309
Mean airway pressure 138, 211, 214
Mean arterial blood pressure 210, 258, 261, 267
Mean systemic filling pressure 128, 129
Mechanical challenges 218
Mechanical energy 156
Mechanical insufflation-exsufflation 229
Mechanical oscillation, high frequency 229
Mechanical power and intensity 157
Mechanical ventilation 19, 33, 61, 90, 114, 137, 153, 161, 178, 198, 210, 220, 228, 231
controlled 164
conventional 223
evolution of 73
graphic analysis of 90
invasive 24, 35, 42
mode of 181
noninvasive 216
weaning from 50, 172
Mechanical ventilator 65, 90, 109f
circuit 108, 181
models of 92
related equipment 227
settings 154f
Meconium aspiration 223
Medical air 66
Medical gases 66
Medical Research Council Score 162
Membrane lung 199
Mental retardation 315
Mesenchymal tumors 309
Metabolic abnormality 350
Metabolic acidosis 246, 311, 329, 331, 333, 335, 351, 360, 361
causes of 333, 335, 358
hyperchloremic 247
normal response for 328
primary 355
severe 84
Metabolic alkalosis 329, 331, 337, 338, 352
causes of 338, 338b
mild 356
normal response for 328
Metabolic cart 366
Metabolic causes 179
Metabolic disorders 328
Metabolic disturbances 37
Metabolic rate, estimate 200
Metabolic regulation 297
Metabolic system 177
Metabolism 37
Methemoglobin 117
Methemoglobinemia 18, 115
Methylene blue 115
test 83
Methylprednisolone 402
Microvascular blood flow 267
Microvascular injury 162
Middle ear barotrauma 25
Milk-alkali syndrome 302, 311
Mineralocorticoid excess, primary 338
Modafinil 43
Molecular diffusion 221
Monarchtm airway clearance system 229
Motor neuron disorders 226
Mucosal cells 119
Mucosal edema 78
glands 3
plugging 32, 33, 34
Multidisciplinary team 227
Multiorgan dysfunction 9
Multiorgan failure 253, 383
Multiple organ dysfunction syndrome 389
Mural alveoli 8
action, direction of 161f
damage 107
dome-shaped 161
fatigability 343
pressure 137
weakness 50, 108, 284
Muscular dystrophy 31
Myasthenia gravis 31
Myocardial dysfunction, acute 399
Myocardial infarction 197, 211
Myocardial necrosis 399
Myocardial stress 135
Myocarditis 197
Myoinositol 283
Myopia, hyperoxic 25
Nail varnish 115
Narcotic overdose 33
Nasal airflow, turbulence of 4
Nasal airway resistance 58
Nasal cannula 18, 19, 20f, 177
high flow 19, 23, 23f, 177, 192
receiving high-flow 192
Nasal catheter 19, 20
Nasal mask 51, 54
Nasal mucosa 4
Nasal pillow masks 51
Nasal prongs 18
Nasopharyngeal mucosa 5
Nasopharynx 4
Natriuretic peptides 238
Natural colloid 247
Near infrared spectroscopy 117
Nebulizers 187
ventilator-compatible 187f
Neovascularization 24
Nerve 162
conduction studies 37
Nervous system 299
sympathetic 238
Neural control 8
Neurologic complications 334
Neurologic diseases, acute 173
Neurologic symptoms 37
Neurological injury 271
blocking agents 162
causes 162, 179
coupling 165
disease 37
disorder 225
progressive 225
efficiency 149
junction, dysfunction of 343
weakness 32, 38
Neurophysiological causes 179
Nitric oxide
extensive 375
generation of 375
inhaled 191
synthase 374
Nitroprusside test 335
Nitrous oxide 71
Nocturnal hypoventilation 55
Nonconventional ventilatory techniques 44
Noninvasive ventilation 19, 24, 41, 47, 48, 49t, 51, 53, 56, 57b, 60, 68, 177, 224, 226
contraindications for 60, 61, 61b
efficacy, signs of 54t
failure, causes of 54
implementation technique 53b
indications for 48b
proper qualification for 57
qualification for 61
rebreathing during 58
receiving 191
Nonrenal potassium loss 288290
Nonstatic variables, multiple 366
Nonsteroidal anti-inflammatory drugs 292, 293
Noradrenaline 402
Normal anion gap metabolic acidosis, causes of 335b
Normovolemia 277
Nucleus tractus solitaries 239
high-risk 368
risk in critically ill score 366t
status 365
Nutritional risk screening 365
Nutritional therapy 365
Obesity hypoventilation syndrome 31, 42, 50
Obstructive airway diseases 77
Obstructive sleep apnea 51, 225, 226
Oncotic pressure, reduced 241
Operation theater 238
cavity, motor innervation of 4
fluids 269
Organ donor after brain death, management of potential 400
Organ dysfunction 288
assessment of 261b
Organ function, monitoring of 262
Organum vasculosum of lamina terminalis 239, 283
Orofacial injuries 52
Oropharyngeal pathway, reduced trauma to 178
Osmosis 236
Osmotic concentration 236
Osmotic demyelination syndrome 280
Osmotic regulation 276fc
Osteoblastic metastasis 299
Osteopenia 314
prevention of 25
treatment of 25
Overhydration 253
Oxidative injury, prevention of 373
Oxidative stress 162, 163, 168
Oxygen 17
administration 41
equipment 227
arterial saturation of 18
concentration 8
analyzers 116
consumption of 27, 198
content of 198, 199
continuous measurement of 114
delivery 18, 27, 115
devices 17, 18, 19t
flush 72
hoods and tents 24
in alveolus, pressure of 29
in arterial blood, pressure of 27, 29
low concentration of 18
mask 177
measurement 114
partial pressure of 197, 198
saturation 18, 25, 114, 122
source 31
species, reactive 24, 154, 156, 163
tank 60
tension in blood, measurement of 115
therapy 17, 57, 60
father of 17
goals of 17
history of 17
to tissues, low delivery of 18
Oxygenated hemoglobin, concentration of 117
Oxygenation, targeted 124
Oxyhood (infants) 19
Packed red blood cell 206, 387, 388
transfusion 387, 388fc
Palliative ventilation 224, 230
acute 299, 367
alcoholic 337
chronic 307
Paranasal trauma 25
adenoma 306
glands 298
surgical removal of 304b
hormone 296, 298, 300, 304, 309, 314, 316
secretion 296
Parenteral nutrition 368, 371
replacement 371t
total 310, 367
Partial pressure
arterial oxygen 48
carbon dioxide 48
Partial rebreathing mask 1921, 21f
Partial thromboplastin time 196
Passive leg raising test 260
Passy Muir valve 228
asynchrony 42, 107
dyssynchrony 164
synchrony 148
system 94
Peak airway pressure 210
Peak and plateau pressure 137
Peak expiratory flow 98
Peak inspiratory
flow 103, 144
pressure 95, 138
Pendelluft 13, 153
Perfusion pressure, abdominal 261
Peripartum cardiomyopathy 197
Peripheral and central chemoreceptors, role of 36
Peripheral capillary oxygen saturation 28, 54, 210
Peripheral nervous system 177
Permissive hypercapnia 37, 42, 44, 217
Persistent pulmonary hypertension 223
pH homeostasis 325f
Pharyngeal reflex 397
Phenytoin 284, 369
Philips Respironics face mask 51f
Phlegm in airways, volume of 54
excretion 311
homeostasis 307
internal redistribution of 308
load 310
renal loss of 308
Phospholipid 9
Phrenic nerve stimulation 147
Physical drug properties 182
Pickwickian syndrome 31
Pillows 51
Plasma 271
colloid oncotic pressure 255
osmolality 239, 255
effective 275
normal 239
osmolar substances in 236f
osmotic pressure of 239
pathogen inactivation of 391
proteins, compartments of 235
renin 291
sodium 283, 283fc, 284
levels 255
volume 236, 238
water 275
Plasma-Lyte 246
Plateau airway pressure 80, 84, 87
Plateau pressure 95, 122, 137, 156
end-inspiratory 138
inhibitor cytochalasin 206
levels 392t
rich plasma 392
transfusion 392
contraindications 392
indications 392
preparation and storage 392
Pleural effusion 33
Plicamycin inhibits 305
Pneumonectomy 83
Pneumonia 33, 43, 98, 346
community-acquired 43, 346
necrotizing 83
reduction in rates of 178
risk of 367
ventilator-associated 50, 172, 226
Pneumothorax 18, 33, 34, 94
with chest tube 83
Poiseuille's law 13
Polymethylpentene 213
Polyunsaturated fatty acids 376
Portal vein, entry of 134
Positive end expiratory pressure 11, 42, 55, 68, 83, 88, 121, 125, 138, 152, 155, 173, 184, 202, 220, 228, 254
intrinsic 37
selection of 82
Positive expiratory pressure 65
Positive fluid balance 269
Positive pressure ventilation 129, 132, 220, 225
effects of 130fc, 135fc
noninvasive 23, 24, 191
Postextubation ventilatory failure treatment 50
Postural hypotension 284
Potassium 244, 296
homeostasis 288, 314
Potato starch 248
Potential airway obstructions 173
Prealbumin 367
Pressure assist control ventilation 69
Pressure carbon dioxide 54
Pressure continuous mandatory ventilation 69
Pressure control 93
ventilation 103f, 104
Pressure measurements 165, 166
Pressure of air, total 349
Pressure sores 87
Pressure support 71, 92
ventilation 66, 70, 84, 142f, 147, 174
mode 71f
Pressure trigger 67, 146
Pressure ulcers 87
mode 110
ventilation 92
ventilation 53, 55, 56, 56f
ventilators 56
Pressure-variable ventilation 60
Pressurized metered-dose inhaler 183, 185
Procainamide myopathy 40
Proinflammatory cytokines 162
Prophylactic transfusion 392
Propylene 334
Prostanoids 191
Protein catabolism 325
Proteolytic pathways, activation of 162
Prothrombin complex concentrate 391
Proton pump inhibitor 315, 316, 369
Pseudohyperkalemia 291, 292, 293
Pseudohyperphosphatemia 311
Pseudohypokalemia 288, 290
Pseudohyponatremia 277
Pseudomonas 190
Psychosis 239
Pulmonary anatomy 182
Pulmonary arterial vasodilation 346
Pulmonary artery 259
catheter 401
occlusion pressure 132, 258, 259
Pulmonary capillary 10
wedge pressure 400
Pulmonary circulation, pathophysiology of 9
Pulmonary compliance 47, 95
Pulmonary complications 226
postoperative 155
Pulmonary drug delivery 185
Pulmonary edema 25, 33, 346, 399
negative pressure 132
of weaning 135
Pulmonary embolism 132, 253, 346
Pulmonary embolus 29, 39
Pulmonary fibrosis 13, 31
Pulmonary function tests 35
Pulmonary gas exchange 28
Pulmonary hyperinflation 78
Pulmonary interstitial emphysema 223
Pulmonary lymphatics 10
Pulmonary oxygen toxicity 25
Pulmonary recruitment maneuver 125
Pulmonary vascular
permeability 259
resistance 129, 130
Pulmonary vasculature 122
Pulmonary venous return 131
Pulmonary vessels 10
Pulsatil oxygen saturation 74
oximeter 114, 114f
oximetry 114, 115t
oxygen saturation 42
pressure variation 128, 131, 133, 134, 134t, 258, 260
calculation of 133f
rate 114
Pulsus paradoxus 131
Pump flow rate 199
Pump in circuit 215
Pump system 214
Pumpless system 214
Purulent fluid, expectoration of 83
Pyrexia, low-grade 358
Radical oxygen species 25
Randomized controlled trial 49, 88, 174, 217
Rapid shallow breathing 14
from pain 33
index 173, 174
Rebreathing, minimize issue of 59
Recruitment maneuvers
advantages of 123
disadvantages of 123
methods of 121
Red blood cell 31, 236, 271
Reflex, hepatojugular 254
Refractory osteomyelitis 25
Regional respiratory mechanics 140
Rehabilitation 178
Renal ammoniagenesis 327f
Renal disease, end-stage 198, 336
Renal failure 300, 336, 371
acute 199
chronic 199
Renal function 255
normal 318fc
Renal loss 315
Renal outer medullary potassium 315
Renal potassium
excretion, disorders of 293
loss 288, 290
Renal regulation 314
Renal replacement therapy 309, 335, 366
continuous 367
Renal response 326
Renal symptoms 38
Renal tubular acidosis 291
Renin angiotensin
aldosterone system 238, 254, 255, 292
system 276
Reproductive system 384
Reservoir cannula 19
Reservoir devices 19
low-flow 20
Resmed nasal mask 51f
Respiration 3
Respiratory acidosis 84, 328, 329, 331, 342, 343, 356
acute-on-chronic 346
causes of 342t
clinical effects 343
etiology 342
management of 344
normal response for 326
Respiratory alkalosis 328, 329, 331, 342, 346, 347, 355
causes of 346
management of 346
normal response for 327
Respiratory arrest 77
Respiratory bronchioles 3, 8, 182
microscopic 3
Respiratory center 31
Respiratory compensation 336, 357
Respiratory cycle 56, 118, 137, 139
total 82
Respiratory dialysis 214, 216
Respiratory disorder 225, 326, 350
Respiratory distress syndrome 344
Respiratory duty cycle 82
Respiratory effects 399
Respiratory epithelia, structure of 4f
Respiratory failure
chronic 351
etiologies of 173
severe 344
Respiratory frequency 176
Respiratory insufficiency 309
Respiratory mechanics 12, 178
pathophysiology of 12
Respiratory mucosa 5
damage, risk of 184
Respiratory muscle 54, 328
fatigue 82, 172
forceful contraction of 6
less fatigued 48
weakness of 37, 82, 168
Respiratory physiology 181
Respiratory portion 3
Respiratory rate 21, 36, 53, 54, 67, 79, 153, 155, 174, 179
effect of 192
Respiratory response 326
Respiratory support 41
Respiratory system 12f, 48, 90, 177, 299, 328
compliance 12, 55, 97, 137
monitor static 84
elastic recoil of 14
end-inspiratory elastic load of 137
physiological pressures of 139f
plateau pressure 156
pressures of 138f
resistance 137
Respiratory tract, structural elements of 3
Resting lung volume 78
Restlessness 284
cardiopulmonary 92, 197
fluids 251
Retrolental fibroplasia 25
Ribonucleotides 373
Right ventricular
ejection fraction 258
area 223
volume 257
Ringer's lactate solution 243
Ringer's solution 245
Rivaroxaban 392
Salbutamol 289
Saline, normal 245
Sclerosis, amyotrophic lateral 226
Secreted albumin remains 247
Sedation with noninvasive ventilation 42
Selenium 373, 381, 382
deficiency 383
guidelines 383
in ICU 383
physiology 381
source 381
toxicity 383
Sensorineural deafness 315
Sensory systems 4
pathophysiology of 270fc
severe 334
Septal dyskinesia 252
Septic shock 270, 360
management of 270
Serotonin release assay 205
bicarbonate 335
level 329
calcium 309
chemistry 39
electrolytes 309
magnesium levels 319t
osmolality 279
phosphate 309, 311
potassium 316
sodium 237, 279
sodium concentration 283
regulation of 275
Severe adult respiratory failure 196
Severe hypercalcemia, classification of 302
Shock 253, 334
hemorrhagic 271
hypovolemic 271
Short bowel syndrome 289, 290, 366
Shunt 29
blood flow 30
equation 30
fraction 11, 30
physiology 28
right-to-left 29
Sick eucalcemia syndrome 301
Sick euthyroid syndrome 400
Sickle cell crisis 18
Sinus 25
Sjögren's syndrome 308
Skeletal disorders 225
Skeletal muscle weakness 31
Sleep disorders 107
Smoke inhalation 25
Smoking 115
Snoring 38
Society of Critical Care Medicine 85
Sodium 244, 285
acetate 246
bicarbonate 283285, 294, 369
chloride 283285, 293, 387
concentrations of 246
solution 245
concentration 335
polystyrene sulfonate 294, 295
reabsorption of 296
Solvent detergent treated plasma 391
Sophisticated transport ventilators 73
Sorbitol 387
Speaking valve 228
Spectroscopy, bioimpedance 238
Spinal anesthesia 241
Spinal cord, traumatic transection of 40
Spironolactone 294
Splanchnic blood flow 120
Spontaneous bacterial peritonitis 272
Spontaneous breathing 55, 151
trial 144, 172, 174, 179
protocol 175fc
Spontaneous ventilations 103
Squamous cell tumors 302
Staphylococcus species 369
Static and dynamic hyperinflation 78
Static transdiaphragmatic pressure, maximum 83
Sterofundin 246
Stewart's approach 331, 354
Stewart's equations 331
Stewart-Fencl approach 351, 352, 355, 360
Stiff lung syndrome 310
Stomach 145
Stomatitis 254
Stress 141
index 124
raisers, mechanism of 153f
Stroke 40
inspiratory down 119f
volume 258
variation 131, 133, 134, 134t, 260
Subclavian artery cannula with graft, right 201f
Subcutaneous emphysema 83
Subglottic larynx 6
Sublingual microcirculation 262
Succinylated gelatin 248
Superior vena cava 134, 200, 256
Supraventricular arrhythmia 320
Surgical emphysema 342
Surrogates 253
Sustained inflation 121, 123
Symptomatic hypercalcemia, severe 302
Syndrome of appropriate deficiency 281
Syndrome of inappropriate antidiuretic hormone 278280, 282
Systemic vascular resistance 400
Systolic blood pressure 400
Systolic pressure variation 131, 133, 258
Tachycardia 284, 399
Tachypnea 41, 43, 48, 78
Tank respirator 65
Tank ventilator 226
Taurine 283
Tension pneumothorax 253
Theophylline 289, 369
Theoretical osmolarity 244
Therapeutic transfusion 392
Thiamine 380
deficiency of 380
Thiazide diuretic 315, 317
Thompson portable respirator 66
Thrombin inhibitor 392
Thrombocytopenia, heparin-induced 198
Thrombocytosis 302
Thromboelastometry, rotational 206
Thromboelastogram 206
Thrombotic thrombocytopenia, heparin induced 205
dysfunction 400
function tests 40
Tidal volume 21, 36, 79, 86, 122, 134, 137, 152, 154, 176, 183
Timed inspiratory effort 146
Tonic-clonic seizures 276, 282
Tonicity 237
regulation of 239
Toxic glycolic acid 334
Toxicology screen 40
Trace elements 381
function of 382t
Trach collar mask 23f
Trachea 183
Tracheal reflex 397
Tracheobronchial lymph nodes 10
Tracheobronchial tree 157
Tracheostomy 43, 178
tube, speaking with 228
Tractus solitaries, nucleus of 239
Tranexamic acid 392
Transbronchial biopsy 83
Transdiaphragmatic pressure 54, 148, 161, 166
Transdiaphragmatic twitch pressure 147
Transesophageal cardiac ultrasound 257
Transfusion trigger 387
Transient receptor potential melastatin 314
Translocational hyponatremia 277
Transmural pressure 128
maintains 129
pressure 128, 139, 141, 148, 151, 157
thermodilution 259
Transrespiratory pressure 151
echocardiogram 125
echocardiography 256
pressure 151
Transtracheal catheter 19, 20
Traumatic brain injury 245, 342, 367, 388
Triiodothyronine 402
Trousseau's sign 300
Tubular necrosis, acute 315
Tubular phosphate reabsorption 311
Tumor 40
lysis syndrome 299, 319
Twitch airway pressure 147
Tympanic membrane, rupture of 25
Tyrosine kinase inhibitor 308
Ulcer disease, active 319
Upper airway 4
in humidification, role of 4
mucosa 5
obstruction 32
trachea 14
Upper respiratory tract, mucosa of 3
Urinalysis 255
Urinary phosphate
excretion 308
measurement of 312
Urinary potassium
assessment of 290
wasting, causes of 295
osmolality 279
sodium concentration 280
Urticarial reactions 394
Vagus nerve 6
Vancomycin 190
Vascular injury 218
Vascular pressures 122
Vasoactive drugs 401
clinical aspect of 240
mechanism of action of 239
receptor inhibitors 284
secretion 239
Vasopressors 173
Vena caval variation 134
Venoarterial venous 200
Venous blood gas 41
Venous collapsibility index 256
Venous flow 10
Venous oxygen
content, mixed 30
saturation 270
Venovenous 196, 215, 216
pulmonary artery 200
pump system 215
Ventilation 1, 28, 206, 215
brief historical recall of 65
continuous mandatory 68, 69
dyshomogeneities, detection of 140
high frequency 84
intermittent mandatory 174
long-term 50, 225t
manual 83
minute 21, 36, 174, 179
modalities of 225
mode and settings 181
monitoring during 79
negative-pressure 226
parameters, adjustment of 57, 61
plus, proportional assist 73
pressure controlled 93
reduces comfort of 54
scintigraphy 83
strategies 86
volume targeted 53, 56, 56f
with intentional leak 60f
Ventilation-perfusion 36
mismatch 191
Ventilator 31, 109
assist, neurally adjusted 73, 146, 148, 149, 166
asynchrony 149
auto-triggering 108
delayed cycling 112
double triggering 107, 108
flow asynchronies 108, 110
breathing circuit 52, 60
circuit 181, 183
disinfection 230
humidification of 183
equipment, care of 229
first-generation 226
induced diaphragm dysfunction
concept of 162
diagnosis of 165
mid-level ICU 67
modern 103
operation 55
patient asynchrony 57
patient synchrony 55
second-generation 226, 231
selection 225
settings 183
supported patients 188
variables 158
Ventilator-assisted patients, long-term 224
Ventilator-induced diaphragm dysfunction
pathophysiology of 163
prevention of 166
Ventilatory failure
after extubation, development of 50
treating acute 49t
Ventilatory management 402
Ventilatory modes 69t
Ventilatory muscles, fatigue of 47
Ventilatory support at night 225
Ventricular assist device 197
Ventricular fibrillation 199
Ventricular function 129
Ventricular interdependence 131
Ventricular septal defect 29
Ventricular tachycardia 199
Vertigo 346
Vibrating mesh nebulizer 188
Vigorous exercise 253
Vili, pathophysiology of 152
Vision 384
changes 25
Vital capacity 48
Vital signs 32
Vitamin 373, 377
A 302, 373
B1 378, 380
B12 378, 381
deficiency 381
physiology 381
source 381
toxicity 381
B6 378
C 369, 373, 377, 378
deficiency of 379
meta-analysis of 377
physiology 377
source 377
use of 379
D 296, 297, 302, 309, 378, 379
deficiency 298, 300, 379, 380
guidelines 380
physiology 379
severe 301
source 379
toxicity 380
E 369, 373
function of 378t
K 378, 391
dependent anticoagulants 391
Vocal cords 5, 6
Volotraumatismes 65
Volume assist-control 35
Volume continuous mandatory ventilation 69
Volume control 93
mode 110
ventilation 96, 101103
Volumetric capnography 119
Volutrauma 83, 141
Vomiting 253, 254, 271, 291, 308
Wall and gas turbine 67f
balance 275, 276, 276fc
compartments of 235
deficit, primary 283
diffuses 236
loss 283
vapor 5
pressure 39
Weaning failure 148, 172
Weaning noninvasive ventilation 42
Weaning success 172
Wernicke encephalopathy 380
Whisper-Swivel connector 59
White blood cell 35
Wilson's disease 308
Winter's formula 353
Winters’ rules 329
Wound healing 383
Xerostomia 254
Zinc 382, 383
deficiency 383
physiology 383
source 383
toxicity 384
Chapter Notes

Save Clear

  1. Respiration: Applied Anatomy and Pathophysiological Considerations
  2. Oxygen Delivery Devices
  3. Approach to the Patient with Hypoxemia
  4. Approach to the Patient with Hypercapnia
  5. Noninvasive Ventilation
  6. Mechanical Ventilators
  7. Mechanical Ventilation in Specific Clinical Scenarios
  8. Graphic Analysis of Mechanical Ventilation
  9. Patient-Ventilator Asynchrony
  10. Monitoring O2 and CO2 during Mechanical Ventilation
  11. Lung Recruitment Maneuvers
  12. Heart Lung Interactions during Mechanical Ventilation
  13. Monitoring Pressures during Mechanical Ventilation
  14. Inspiratory Effort Assessment in Ventilated Patient
  15. Ventilator-induced Lung Injury
  16. Ventilator-induced Diaphragm Dysfunction
  17. Weaning from Mechanical Ventilation
  18. Aerosol Drug Delivery in Ventilated Patient
  19. Extracorporeal Membrane Oxygenation
  20. Extracorporeal Membrane Carbon Dioxide Removal
  21. High Frequency Oscillatory Ventilation
  22. Domiciliary and Palliative Ventilation2

Respiration: Applied Anatomy and Pathophysiological ConsiderationsCHAPTER 1

Alex Yartsev,
Yugan Mudaliar
The macroscopic and microscopic anatomy of the respiratory tract is inseparable from its physiological function, and has significant relevance to the study of human respiratory pathophysiology. Applied respiratory anatomy and physiology is of fundamental importance to critical care, given the prevalence of respiratory conditions and complications among critically ill patients, and the frequency of the need for interventions directed at the respiratory system. This chapter focuses on those aspects of respiratory tract anatomy and physiology which are most relevant to the routine practice of critical care medicine, and which have the greatest impact on the management of a patient with severe respiratory pathology.
The respiratory tract consists of mouth, nose, pharynx, larynx, trachea, bronchi, alveoli, and pulmonary vessels. Of these structural components, many have important roles which are not directly involved in respiration and gas exchange. For instance, the mouth and tongue have important roles in speech and swallowing, the nose in humidification, the trachea in the cough reflex, and the alveoli in the synthesis of angiotensin-converting enzyme (ACE).
The upper airway trachea and bronchi form the “conductive portion” of the respiratory system, so named because the function of these structures is not directly related to gas exchange. The macroscopic and microscopic structure of these components bears a direct relationship to their role as rigid conduits for gas, and the defenders of the delicate lower structures from thermal and physical insult. The “respiratory portion” of the respiratory tract consists of respiratory bronchioles and alveoli. These structures serve to maintain a low resistance to airflow as well as participating directly in gas exchange.
The histological structure of the respiratory tract is no less relevant to function and also calls for a detailed discussion. The mucosa of the upper respiratory tract is well-supplied with capillary blood flow and is an important route of drug delivery. Moreover, its epithelial layer harbors immunoglobulin molecules (predominantly IgA), numerous quiescent lymphocytes, and dendritic antigen-presenting cells (APCs), playing an important role in specific cellular and humoral immunity. Mucous glands and Bowman's glands in the epithelium produce secretions which moisturize the cellular layer and contribute to the humidification of the inspired gas. Lower airways are well-supplied with ciliated columnar epithelium to promote the outward movement of mucus, assisting in the clearance of small particles (Figs. 1A to C).
The respiratory portion of the respiratory tract consists of microscopic respiratory bronchioles and alveoli, the histology of which bears a direct relationship to the function of gas exchange. Respiratory bronchioles contain the smooth muscle, which acts as an important target for bronchodilators. Understanding the cellular structure of alveoli is of paramount importance to the understanding of gas exchange. The physical properties of alveoli and the actions of alveolar surfactant (secreted by Type 2 alveolar cells) are vital to the understanding of clinical approaches to the mechanical ventilation for acute respiratory distress syndrome (ARDS), as well as complications of mechanical ventilation such as barotrauma and biotrauma.
The evolution of the human airway from precursor structures in earlier animals and fish has led to a single cavity that serves the purposes of speech, air intake, and swallowing.14
zoom view
Figs. 1A to C: Microscopic structure of the respiratory epithelia. (A) The upper respiratory tract is lined with pseudostratified columnar epithelium; (B) The bronchioles are lined with ciliated cuboid epithelium; (C) The alveolar epithelial lining consists of Type 1 and Type 2 alveolar cells.
As such this cavity is a complex organ complete with multiple motor and sensory systems, which permit the isolation of these functions, with the resulting inability of human beings to speak, swallow, and breathe at the same time. The motor innervation of the oral cavity and pharynx enjoys a significant amount of central control. From the point of view of the critical care physician, the most important pathophysiological implications of this control is the loss of protective airway reflexes and pharyngeal muscle tone which is associated with a decreased level of consciousness.
The Effect of Depressed Consciousness on Oropharyngeal Patency
The fact that a depressed level of consciousness can give rise to asphyxia due to airway obstruction is a well-recognized feature of advanced life support training. The pathophysiological mechanism underlying such airway obstruction is complex. Though relaxation of the tongue plays a role in obstruction at the level of the pharynx, closure of the laryngeal entrance by the epiglottis is the main cause of airway closure associated with unconsciousness. Cadaveric studies where the tongue was removed had demonstrated that an airtight seal could be achieved by the closure of the epiglottis alone.2 The most important implication of this finding in critical care is the observation that elevation of the mandible-hyoid apparatus by jaw thrust relieves both causes of obstruction.
The nasal cavity turbinates serve to increase the turbulence of air flow, thereby increasing the contact of inspired air with the nasal mucosa. The effect of this is to increase the temperature and humidity of inspired air, protecting the mucosa of lower passages from dehydration.
The anterior nares feature coarse hairs, called vibrissae (though the term usually applies to mammalian sensory hairs from which human nasal hair differs in both structure and function). These hairs arise from follicles which are similar to hair follicles elsewhere on the skin, and are neither richly innervated nor mapped onto the somatosensory cortex, in contrast to the mystacial vibrissae of mammals. These hairs are thought to serve the purpose of increasing the turbulence of nasal airflow as well as trapping inhaled macroscopic particles. The importance of these hairs in the critical care environment is seen in the context of airway burns; singed vibrissae are a signal that inhaled gas or smoke was sufficiently hot to be associated with a high risk of airway burns.3
The Role of the Upper Airway in Humidification
The upper airway is able to warm and humidify inspired air over an enviable range of temperatures and ambient humidity levels. By the time it reaches the carina, inspired gas may be heated by 20–30°C during its passage through the upper airways, and inspired air as cold as −100°C achieves core body temperature and 100% humidity by 5the time it reaches the alveoli.4 This exchange of heat and moisture occurs in both directions: On expiration, heat and moisture are reclaimed by the mucosa, and expired air has its temperature reduced from 37°C at the alveoli to 32°C at the nares. The expired air remains 100% saturated with water vapor, but as its temperature decreases, so does its absolute water content.5
The efficiency of heat and moisture exchange in the nasopharynx is increased by means of turbulent convection. Turbulence increases the contact between inspired air and nasopharyngeal mucosa, promoting increased heat exchange. At the same time, increased contact with inspired air promotes the evaporation of water from the mucosa. As heat is exchanged and inspired air increases in temperature, its capacity to “hold” water vapor also increases, until an equilibrium is reached where the inspired air is isothermic with the mucosa, and 100% saturated. This occurs at the “isothermic saturation boundary”, at a level just below the carina during normal quiet breathing. At this level, the absolute humidity is 47 g/m3.
The importance of maintaining humidification of the respiratory gases is twofold. It maintains the health and barrier integrity of the respiratory mucosa, and allows effective gas exchange. This has implications for the critical care environment, where mechanical ventilation often requires the use of piped gas supplies. The administration of dry cold gas (for instance, oxygen directly from the compressed gas storage system) leads to the inspissation of secretions, dehydration of the nasal mucosa, failure of the mucosal barrier function, an increased risk of epistaxis, as well as the thickening of the lower respiratory tract mucus layer, and the impairment of mucosal ciliary motility.6
For these reasons, in mechanically ventilated patients, humidification of inspired gas mixtures needs to be maintained, particularly if the upper airways have been bypassed by endotracheal intubation or tracheostomy. This can be accomplished by means of passive heat and moisture exchange filters which replicate the functions of the upper airway mucosa, or by active humidifiers which pass the inspired gas mixture across a heated water bath. In order to maintain mucosal integrity and enhance secretion clearance, a humidity output of 30 g/m3 is recommended for long-term intensive care unit (ICU) use and 20 g/m3 for short-term perioperative ventilation.7
The larynx is a cartilaginous tubular structure which acts as the entrance to the trachea and functions to occlude the airway. In evolutionary terms, it had developed from the airways of the lungfish, and had served to protect the air-filled cavities of the respiratory system during feeding and perfusion of the gills with water.8 Similarly, the human larynx has multiple functions all of which in some way involve occluding or obstructing the flow of air in and out of the trachea. These functions include phonation (the laryngeal component of speech), effort closure (for forceful expulsion of lung air, as in coughing), and swallowing (where the larynx is elevated and epiglottis closes the laryngeal inlet, directing the food bolus backward into the esophagus).
The anatomy of the larynx as relevant to the practice of gaining airway access has paramount importance to the critical care physician. Figure 2 demonstrates the anatomical features of the adult larynx from the point of view of direct laryngoscopy. Anatomically, the larynx extends from the tip of the epiglottis to the inferior border of the cricoid cartilage. It is suspended from the hyoid bone, and is found at the level of the C3–C6 cervical vertebrae. Its rigid structural components consist of three single cartilages (thyroid, epiglottic, and cricoid) and three paired cartilages (arytenoid, cuneiform, and corniculate). In terms of importance to airway access, the most important cartilaginous structure is the epiglottic cartilage, a long teardrop-shaped cartilage which is attached anteriorly to the hyoid bone by the hyoepiglottic ligament.9 Pressure in the vallecula during direct laryngoscopy elevates the epiglottis and affords a direct view of the vocal cords. Position of the epiglottis during laryngoscopy describes the difficulty of intubation by the Cormack–Lehane descriptive system,10 ranging from Grade 4 (where not even the epiglottis is visible) to Grade 1 (where the epiglottis is completely elevated and most of the glottis can be visualized).
The larynx moves under the influence of intrinsic muscles that control the vocal cords and the extrinsic muscles which change the position of the larynx in relation to the hyoid and sternum to assist in swallowing.9 Of the intrinsic muscles, all receive motor innervation from the recurrent laryngeal nerve except for the cricothyroid muscle (which increases tension on the vocal cords, and for which is motor innervation is supplied by the external branch of the superior laryngeal nerve). Damage to the recurrent laryngeal nerve produces paralysis of the ipsilateral intrinsic muscles, sparing the cricothyroid muscle. The resulting unopposed tension on the vocal cords can give rise to hoarseness or stridor with unilateral lesions and airway obstruction with bilateral recurrent laryngeal nerve injuries. Outside of surgical scenarios such as thyroid surgery, a likely cause of recurrent laryngeal nerve injury in the ICU is an endotracheal tube cuff which has been inflated in the subglottic larynx. The recurrent laryngeal nerve enters this area between the cricoid and the thyroid cartilage, and is susceptible to injury where an inflated cuff can compress it against the overlying thyroid cartilage.116
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Fig. 2: Anatomy of the larynx as viewed for laryngoscopy.
Laryngospasm and Protection from Aspiration
The larynx is richly innervated by the superior laryngeal nerve and the recurrent laryngeal nerve, both are the branches of the vagus nerve.12 Sensory innervation to the glottis and the glottic vestibule is supplied by the internal branch of the superior laryngeal nerve. The lower glottis sensory and motor innervation comes from the recurrent laryngeal nerve. The density of laryngeal sensory chemoreceptors and mechanoreceptors is greatest at the laryngeal opening, which allows rapid protective responses.
The stimulation of these receptors leads to the reflexive closure of the glottis by adduction of the vocal cords, which functions to protect the lower airways from foreign material. When this adduction response is long-lived, it may render ventilation impossible. Such a sustained closure of the true vocal cords (or both true and false cords) is described as “laryngospasm”.13 Failure of the afferent or efferent components of the laryngeal closure reflex (e.g. following stroke) may give rise to aspiration of upper airway secretions and subsequent pneumonitis.
The Effect of Endotracheal Intubation on Cough
A normal cough sequence consists of deep inspiration, glottic closure, increase in transpulmonary pressure by forceful contraction of respiratory muscles, and ultimately glottis opening with an abrupt increase in airway gas flow. The tracheal lumen collapses and in the narrowed trachea the high peak air flow results in the expulsion of 7tracheal secretions. In the intubated state, glottis closure is not available, and normal cough efficiency is altered by the disruption of normal flow and pressure timing. The intubated patient is still able to transport secretions to the trachea, but failure of the trachea to collapse prevents the necessary high flows from being generated, with the resulting accumulation of secretions near the distal end of the endotracheal tube.14 This has significant implications for secretion control and management of pulmonary infection in intubated patients.
The Effect of Tracheostomy on Swallowing Function
A key function of the laryngeal apparatus is to permit airway closure during swallowing by the elevation of the larynx. The laryngeal inlet is both closed and physically removed from the path of the food bolus by action of a number of muscles, which are grouped under the term “laryngeal strap muscles” and which contribute to the suspension of the larynx.15 This movement is permitted by the natural elasticity and mobility of the trachea. The presence of a tracheostomy tethers the larynx by immobilizing the trachea against the skin and strap muscles of the neck, inhibiting the normal upward excursion of the larynx.16
Trachea and Bronchi—The Conductive Airways
The tracheobronchial tree is a series of tubular respiratory passages consisting of complete and incomplete cartilaginous rings as well as smooth muscle and the striated trachealis muscle. The tree branches into 23 “generations” of successively narrower airways with a progressive increase in the total cross-sectional area, from the 1.8 cm diameter of the trachea (generation 0) to the respiratory bronchioles (generations 17–19), which are approximately 0.4 mm in diameter (Fig. 3). As the total cross-sectional area of the lower airways may be up to 100 times that of the upper airways, the resistance to air flow in these regions is usually minimal.
Among the functions and structural properties of the tracheobronchial tree, of greatest pathophysiological importance to the critical care physician is the immune function of the mucociliary escalator and the role of bronchial smooth muscle tone in generating resistance to air flow.
Mucociliary Escalator
The “mucociliary escalator” consists of a ciliated epithelial layer, which extends from the larynx to the terminal bronchioles (the 16th division of the tracheobronchial tree). This ciliated layer is the primary defense mechanism of the lower respiratory tract against inhaled particulate matter. The cells of this layer consist of ciliated columnar epithelial cells (each featuring approximately 200 cilia) and mucus-secreting goblet cells (Fig. 4). The secretions of the cells (4% mucus and 96% water by weight) form a layer over the cilated epithelium. Rather than a continuous mucus layer that covers the epithelium like a blanket, discrete islands of respiratory mucus float on a layer of periciliary sol like lilies on water; the sol forms a thinner fluid that allows the cilia to beat and thus propel the mucus islands up the airway.17 The coordinated movement of the cilia is a surprisingly powerful force and can carry masses up to 10 g cm−2 against gravity,18 at velocities of approximately 5–20 mm per minute.
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Fig. 3: The cross-sectional area of the airways is narrowest at the junction between the lobar and segmental bronchi, and increases exponentially in the lower airways.
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Fig. 4: Respiratory pseudostratified columnar epithelium of the trachea. The mucus layer sits atop an aqueous sol, in which the mobile cilia are situated.
Increased susceptibility to pneumonia among ventilated patients has been attributed an impairment of the mucociliary escalator action. Intubated patients have slowed mucociliary clearance (down to 1 mm/min), and mucous flow may even be reversed in the semirecumbent position, which may contribute to the pathogenesis of atelectasis and ventilator-associated pneumonia.19,20 High oxygen concentrations, poor humidification, systemic inflammatory response, colonization by bacteria, suction catheter damage to the mucosa, and bacterial colonization have all been implicated as possible causes of this mucociliary clearance impairment.
The Role of Bronchial Smooth Muscle in Bronchospasm
Bronchi and bronchioles (generations 4–14) feature crisscrossing helical bands of muscle, the thickness of which is proportionally greatest at the level of the bronchioles.21 These bands of muscle can alter the diameter of the small airways in response to local cellular factors, mechanical and chemical stimuli, and neural control or humoral circulating factors. The cross-sectional area of the distal bronchi may decrease by 50–80% at maximal bronchoconstriction; the degree of bronchoconstriction increases with increasing bronchial generations,22 which has implications for drug delivery. Inhaled bronchodilator particle size needs to be sufficiently small in order to penetrate to these deeper structures.
Alveolar Ducts and Alveoli
The terminal bronchioles are the last generation of conductive airways. Beyond these, the airway branches into respiratory bronchioles, alveolar ducts, and alveolar sacs. Like the terminal bronchioles, the respiratory bronchioles have a well-defined smooth muscle layer; however, with increasing generations respiratory bronchiole walls gradually increase in the number of mural alveoli. The alveolar ducts differ from respiratory bronchioles by having no walls (i.e. their walls consist only of the openings of mural alveoli). Alveolar sacs are the terminal branches of the respiratory tract. Approximately half of all alveoli take their origin from alveolar sacs, the other half originating from alveolar ducts. The total number of the alveoli is on average approximately 480 million, and each is approximately 0.2 mm in diameter at functional residual capacity (FRC). Each alveolus is usually polyhedral rather than spherical; the septa between alveoli are stretched tight by the tension of the elastic fibers they contain as well as by the surface tension created by the air–fluid interface. These septa contain pores of Kohn, microscopic fenestrations which permit the movement of gas between alveoli (Fig. 5). The alveolar septa also contain the pulmonary capillaries, which bulge into the airspace. The thickness of the active membrane here is 0.2–0.3 µm, and there is virtually no interstitial space.
Alveolar epithelial cells (Type I cells) have a flat sheet-like structure, mostly devoid of organelles and of approximately 0.1 µm in thickness. They are joined together by tight junctions, which prevent the escape of large proteins into the alveolar space. These cells do not have the capacity to undergo mitosis. Type II cells are the stem cells from which Type I cells arise; these serve to replenish the alveolar epithelium as well as being sources of alveolar surfactant.
Alveolar Surfactant
Alveolar surfactant is a surface-active material, which is responsible for maintaining the low surface tension of alveolar fluid. Surfactant consists of one main active ingredient (dipalmitoylphosphatidylcholine, a phospholipid) as well as carbohydrates and a small amount of surfactant proteins (2% by weight).9
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Fig. 5: Functional cellular anatomy of the alveoli.
Surfactant is released by Type II cells, has a half-life of 15–30 hours, and is degraded by reuptake into Type II cells. The clinical relevance of surfactant is apparent in surfactant-deficient pathological states, of which the prototypic model is a preterm neonatal lung. Severe respiratory failure with atelectasis tends to develop in premature infants who are yet to secrete enough surfactant23 and those suffering from hereditary disorders of surfactant protein synthesis.24 The presence of surfactant in bronchoalveolar lavage fluid can be confirmed by the presence of foam in the retrieved fluid, and indicates a deep lavage. However, the excessive washout of surfactant can give rise to postlavage hypoxia and atelectasis. Lastly, pulmonary surfactant interacts destructively with lipopeptide antibiotics such as daptomycin, resulting in their deactivation.25
Ventilator-associated Lung Injury at the Alveolar Level
The alveolar septa derive their durability from a basement membrane layer (the lamina densa) composed of Type IV collagen fibers. This layer is approximately 50 nm thick and is adherent to the epithelial (respiratory) and endothelial (vascular) cells on either side by a network of attachment proteins called laminins. These proteins interact with the cytoskeleton of endothelial and epithelial cells, regulating the permeability of the membrane.
Mechanical ventilation with high pressures can damage the alveolar septa. Microscopically, there is damage to both alveolar epithelium and pulmonary capillary endothelium. At ventilation with pressures greater than 30 cm H2O, there is flattening of alveolar capillaries, and visible disruption of the epithelial and endothelial layers. The basement membrane usually remains intact (and may be the sole remaining barrier between gas and blood). However, the diffusion of gases is still impaired because the membrane is usually thickened (up to 1 µm) due to cellular damage and resulting interstitial edema. At higher pressures (up to 50 cm H2O) the basement membrane can also be damaged, and microscopy of alveoli ventilated at such pressures reveals a full-thickness of red blood cells in the alveolar spaces.26 It would appear that the elastic collagen-rich basement membrane has a greater tolerance for mechanical stress, but the damage to endothelial and epithelial cells manifests at lower pressures. This cellular damage then gives rise not only to a degraded gas diffusion due to increasing membrane thickness, but also to a release of proinflammatory mediators into the systemic circulation. The systemic effects of such cytokine release are seen in mechanically ventilated patients with ARDS; the phenomenon has been called “biotrauma” and can lead to multi-organ dysfunction.27
The anatomical distinction between the pulmonary and systemic circulation lies in the different pressures between these two systems. The blood pressure within the pulmonary circulation is approximately 15–20% of the systemic arterial blood pressure. Consequently, pulmonary vessels have significantly less smooth muscle; in fact, the larger vessels are composed mainly of elastic 10connective tissue. Muscular layers become dominant in pulmonary arteries below 1mm diameter. In contrast to systemic arterioles, pulmonary arterioles have minimal smooth muscle tissue in their walls, and are structurally indistinguishable from pulmonary venules. Pulmonary arterioles and venules frequently have small (25–50 µm) anastomoses which remain closed under normal conditions and only open into shunts under conditions of increased cardiac output or with the use of inotrope agents.28 Shunt, pulmonary hypertension, and their management are discussed in greater detail elsewhere.
Pulmonary capillaries form a dense network in the alveolar septa, and a capillary network may span several alveoli before emptying into a pulmonary venule. Pulmonary venules run along segmental septa. Pulmonary vessels and bronchi are surrounded by a network of pulmonary lymphatics, which occupy potential spaces between these structures and the rest of the lung parenchyma. During episodes of pulmonary edema, these potential spaces become distended with fluid, giving rise to the characteristic peribronchial cuffing seen on chest radiographs. Lymphatic drainage occurs in the direction of the hilum, also giving rise to the perihilar hazing and “bat-wing” appearance of acute pulmonary edema. Tracheobronchial lymph nodes accept drainage from pulmonary lymphatics, and these groups of nodes (particularly the subcarinal nodes) become attractive targets for bronchoscopic biopsy sampling.
Ventilation and Perfusion Relationship
In ideal circumstances, alveolar ventilation (V) and alveolar capillary perfusion (Q) would be perfectly matched; i.e. the ideal alveolus is ventilated with the perfect amount of air in order to completely saturate all hemoglobin molecules passing through its capillaries. In reality, there is a regional variation of blood flow and ventilation which varies with posture, disease states, drug effects, and mechanical ventilation.
Perfusion is maximal in dependent regions of lung, which in the upright position are the lung bases. According to this “gravitational model”, in upright man the perfusion of the lung apices can be attributed to the difference in hydrostatic pressure between the apices and the bases, which may be 30–40 cm H2O.29
Ventilation is also maximal in the bases of the lungs, where the rib cage expands to the greatest extent in inspiration, and where diaphragmatic excursion contributes to the change in volume. Furthermore, lung tissue has a significant mass and therefore the weight of the tissue above compresses the tissue below; the dependent lung is therefore more compressed, has higher compliance and therefore better ventilation. In the upright position, the measured ratio of apical to basal ventilation is approximately 1:1.5 by volume at resting ventilation, and 1:3 at inspiration to full vital capacity.
Zones of the Lung, Dead Space and Shunt
Regional differences in ventilation and perfusion give rise to three distinct patterns, which are known as Wests’ Zones. Because the pulmonary circulation is a low pressure system, in the apices the pulmonary capillary pressure may be lower than alveolar pressure; this results in areas of lung which are ventilated but not perfused, referred to as alveolar dead space. This region is referred to as Wests Zone 1; the pattern of V/Q mismatch described by this zone does not occur in normal physiological states, but may be seen in critically ill patients suffering from extreme hypovolemia or hemorrhagic shock.30 It can also be seen in circumstances where alveolar pressure is artificially increased, for instance in the context of mechanical ventilation with high pressures.
Wests Zone 2 describes a region which has pulsatile blood flow which is generated by the fact that pulmonary venous pressure is lower than pulmonary arterial pressure. In this region, flow occurs intermittently, when arterial pressure cyclically increases to a point where it overcomes the obstruction to venous flow. After the pressure is relieved, the system returns to a low pressure state and flow ceases again.
Wests Zone 3 describes an area of the lung where the capillaries enjoy constant blood flow because both arterial and venous pressure is higher than the alveolar pressure. This relationship describes blood flow in the dependent basal regions of the lung. Because there is an uninterrupted column of blood between the pulmonary arteries and the pulmonary veins in this region, Zone 3 makes an ideal position for measuring pulmonary capillary wedge pressures using a pulmonary artery catheter.
In disease states such as atelectasis or pneumonia, regions of lung will have minimal ventilation due to physical compression, bronchial obstruction, or copious secretions. In this case, the affected regions of lung will have perfusion, but no ventilation. Pulmonary veins returning from such regions will carry hypoxic blood back into the systemic circulation, and the addition of this hypoxic blood will reduce the oxygen saturation of arterial blood in the systemic circulation. This phenomenon is referred to as intrapulmonary shunting, and the resulting incompletely 11oxygenated percentage of cardiac output is described as the shunt fraction.
Static lung volumes and capacities have standard definitions (Fig. 6), where a “capacity” refers to a measurement consisting of more than one “volume”.
The total lung capacity (TLS) is the volume of gas in the lungs at the end of a maximal inspiration. The residual volume (RV) is the volume which remains after a maximal expiration. The functional residual capacity (FRC) is the volume of gas which remains in the lungs after an expiration during normal breathing. Lung volumes are affected by age, gender, ethnicity, posture, obesity, and pregnancy; they change in linear proportion with the height of a patient. During mechanical ventilation, tidal volume is usually calculated with reference to the ideal body weight, which is indexed to height.
Volume-Related Airway Collapse and Closing Capacity
Lung volumes influence the diameter of smaller airways, particularly those beyond generation 11 (as these have minimal cartilage and rely instead on the traction from lung tissue for their patency). As lung volume decreases in expiration, the volume of all air-filled cavities and passages decreases proportionally, which includes the smaller airways. As lung volume decreased toward RV, some of these smaller airways begin to close, which results in an increase in their resistance to airflow.32 At some critical volume, these small airways collapse completely; the volume at which this occurs is referred to as closing capacity, and the effect of lung volume on increasing airway resistance is referred to as volume-related airway collapse. Closing capacity increases with age; it is well below the FRC in young patients, but becomes equal to FRC in patients over 70, even in the upright posture.33 With the closing capacity exceeding FRC, during a period of expiration some of the alveoli will be perfused with pulmonary blood but not ventilated because of airway closure, which represents a shunt by definition. This is most marked in dependent regions of lung and in situations where the FRC is decreased (e.g. in obese patients, in pregnancy or when the patient is in a supine position). One of the effects of positive end-expiratory pressure (PEEP) is to increase the FRC above closing capacity, thereby decreasing shunt and improving oxygenation.
Flow-Related Airway Collapse and Closing Capacity
Gas flow influences the diameter of smaller airways; even the trachea changes diameter with high expiratory gas flow velocity.34 During forceful expiration, the normally negative intrathoracic pressure becomes positive with the effort of expiratory muscles, resulting in a high velocity gas flow out of the lung. Along the path of gas flow out of the lung, there is a pressure drop (as the resistance to airflow decreases with decreasing generations of airways). Therefore, at a point in the airway, the airway pressure will be equal to the intrathoracic pressure (this point is referred to as the equal pressure point). Beyond that point, intrathoracic pressure may be greater than the airway pressure, which (unless the airway is endowed with rigidity by structural cartilage) will result in airway collapse. This effect is most prominent in airways already narrowed by disease (e.g. asthma), in dependent regions of lung, and at small lung volumes near closing capacity, where airway diameter is already decreased. One of the effects of PEEP is to oppose positive intrathoracic pressure (e.g. due to “intrinsic PEEP” in asthma), thereby allowing airways to remain open.
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Fig. 6: Static lung volumes.31
“Respiratory mechanics” is a term conventionally applied to the interaction of pressure and flow in determining respiratory function. Pressure and flow are determinants from which a variety of indices may be derived, such as volume, compliance, resistance, and work of breathing. These parameters are of substantial importance in the critical care setting, where they are amenable to manipulation by means of mechanical ventilation.35
The respiratory system is composed of several interacting anatomical components, which can be functionally divided into airways, lungs, chest wall, and abdomen. Gas flow through the respiratory system is determined by pressure gradients, which are generated by the interaction of these anatomical elements. In order for gas flow to occur there needs to be a pressure gradient between the atmosphere and the alveoli. This pressure gradient across the lung (PL) represents the difference between pressure at the airway (Pao) and pressure in the pleural space (Ppl). As there is no convenient method to monitor pleural pressure directly, esophageal balloon manometry may be used as an acceptable surrogate.36 For the intents and purposes of bedside physiology, Ppl = Pes. Thus,
PL = Pao– Pes
Thus, a negative pleural pressure must be generated by the respiratory muscles in order to produce a flow of atmospheric gas into the system. In the mechanically ventilated patient, positive pressure applied at the airway opening produces a positive pressure gradient which drives the flow of gas. Outward flow during expiration occurs passively, and is the consequence of elastic structures recoiling into their resting state (these structures include the lung parenchyma, chest wall, and the abdomen). The amount of pressure which needs to be generated by the patient (or applied by the ventilator) in order to produce gas flow is determined by pulmonary compliance and respiratory system resistance.
Respiratory system compliance is determined by the equation,
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where ΔV is the change in volume, Pplat is the plateau airway ΔV pressure, and C is compliance expressed in terms of volume per unit pressure (classically as mL/cm H2O). Normal static compliance in a mechanically ventilated patient is generally held to be 50–100 mL/cm H2O.
Response of the respiratory system to distending pressure is nonlinear, and can be represented by a sigmoid curve. Ventilation typically occurs in the range of tidal volumes where compliance of the respiratory system is high (the “steep” portion of the pressure–volume curve); ventilation with higher volumes or higher pressures may lead to overdistension and a loss of lung compliance is seen, i.e. higher pressures produce a smaller increase in volume (Fig. 7).
Compliance may be further divided into static and dynamic compliance. Conventionally, discussions of compliance address static compliance alone, in the context of a respiratory system inflated with a static volume of gas. However, the process of mechanical ventilation is a dynamic process where inward and outward flow is constantly alternating. The compliance of this system is described by the term “dynamic compliance”, which is described by the equation,
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Fig. 7: Pressure and volume relationships in the respiratory system. The dashed line represents expiratory pressure and volume relationships. Note that as the tidal volume approaches total lung capacity, incremental increases in pressure produce ever-diminishing increases in volume.
where Ppeak represents the peak inspiratory pressure. Peak inspiratory pressure is the sum of pressure generated in overcoming lung compliance and pressure generated in overcoming respiratory resistance.
The anatomical and physiological determinants of static compliance are the elasticity of lung tissue and alveolar surface tension. These may be altered in disease states. For instance, decreased respiratory compliance is seen in states of surfactant deficiency (for instance, in premature neonates, or in patients recovering from bronchoscopic lavage). Pulmonary disease which decreases compliance may do so in a diffuse manner (e.g. the effects of ARDS) or by decreasing the total lung capacity by obliterating aeration of whole regions of lung (e.g. the effects of lung consolidation). Destructive pulmonary parenchymal disease may also have the effect of increasing lung compliance, as in the case of emphysema. Unique approaches to the management of mechanical ventilation in states of extremely poor lung compliance (such as ARDS) are discussed in later chapters.
Resistance, broadly speaking, is a resistance to motion. The respiratory system is resistant to the flow of gas. The determinants of this resistance and their proportional contributions are friction against airway surfaces (80%), tissue resistance (19%), and forces of inertia (1%). The resistance to airflow is, therefore, determined largely by the resistance of airways.
The relationship of airway diameter to airway resistance and the pressure generated thereby is described by Poiseuille's Law:
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where ΔP is the change in pressure generated by the resistance, Q is the flow rate of the gas, η is the viscosity of the gas, L is the length of the airway, and r is the radius of the airway (which is assumed to be cylindrical in cross-section). By this relationship, the greatest airway resistance is to be expected at the transition point between lobar and segmental bronchi (generations 3, 4, and 5) where the total cross-section of the airways is the smallest (Fig. 3). Measurement and imaging of airways37 has confirmed that 80% of total airway resistance is generated at this level.
Physiological changes in the respiratory system can influence airway resistance. For instance, airway resistance is inversely proportional to lung volume. Beyond the conducting airways, airflow resistance becomes dependent on lung volume. In inspiration, the expanding lung also puts distending pressure on the smallest airways by traction, therefore increasing their diameter and decreasing their resistance. Conversely, forced expiration increases airflow resistance by increasing pressure on these small airways, forming flow-limiting segments.
Pathological states can also influence airway resistance. Notably, asthma and anaphylaxis can give rise to marked reversible increases in airway resistance. Irreversible or incompletely reversible increases in airway resistance are associated with disease states such as chronic obstructive pulmonary disease (COPD). Unique approaches to the management of bronchospasm and mechanical ventilation in states of extremely high airway resistance are discussed in later chapters.
Time Constant
Idealised models of lung function behold the lung as a perfectly elastic solid, which instantly expands by a volume (ΔV) in response to the distending pressure (ΔP). The properties of lung in vivo are not ideal, and lung tissue takes some time to distend to ΔV. The time required to distend the lung up to 63% of the maximal inflation or deflation is referred to as the time constant (τ), and is described mathematically as:
τ = C × R
where C represents compliance and R represents resistance. The value of this constant varies across lung units, and between inspiration and expiration. Lung units with a high compliance and high resistance (e.g. emphysema and COPD) fill slowly, empty even more slowly, and this is represented by a longer time constant (τ) value. Conversely, lung units with poor compliance and low resistance (e.g. pulmonary fibrosis, ARDS) have a quick τ value, filling and emptying rapidly.
The concept of time constant has relevance with relation to positive pressure ventilation. As the lung is distended during a mechanical breath, the greatest part of the tidal volume will be distributed into lung units with the lowest (quickest) τ value. Even if the ventilator has cycled to inspiratory pause or expiration, gas may continue to redistribute from these “quick” lung units into “slow” lung units, a process referred to as pendelluft. This has the effect of reducing dynamic lung compliance and worsening oxygenation. As lung units with poor compliance and low airflow resistance fill the fastest, they will contribute to a rapid rise in pressure with the initiation of the mechanical 14breath. Gas, which subsequently redistributes from these units, has already participated in gas exchange and therefore will have a higher PCO2 and a lower PO2, diluting fresh gas and thereby impairing effective gas exchange.38 Though likely to have minimal adverse influence on gas exchange physiology in the healthy subject, time constant may play a significant role in the physiology of the critically ill patient, particularly hypoxemic patients with severe COPD. This has implications for the approach to ventilation in such patients; classically a prolonged expiratory phase is programmed into the ventilator in order to allow for the lung units with low time constant to empty.
Work of Breathing
The definition of work is the product of force and distance, or in the case of the respiratory system the product of pressure and volume. The commonly used term “work of breathing” is something of a misnomer as it is usually used to describe the power of breathing, which is defined as work per unit time, and where the respiratory rate is also incorporated. Work of breathing can be expressed in joules per liter, which is energy required during one breath cycle divided by the tidal volume in liters. Alternatively, power of breathing can be expressed in joules per minute, which is the energy in joules per breath cycle multiplied by the minute respiratory rate. The work and power of breathing of a normal healthy patient is approximately 0.35 J/L, or 2.4 J/min.39 The main determinants of the work of breathing are elastic recoil of the respiratory system and the resistance to airflow.40
Work against the elastic recoil of the respiratory system is used to expand the chest and distend the lung parenchyma. During normal quiet breathing, approximately half of the energy is spent on this (and is stored as potential energy, to be used during the passive expiratory phase) and the other half is dissipated as heat in the process of overcoming frictional forces.
Work against airway resistance is spent to overcome the frictional resistance to airflow. Additional negative intrathoracic pressure needs to be generated in order to create a sufficient pressure gradient and overcome resistance to inspiratory flow.
Under normal conditions, only the inspiratory muscles perform any work (by storing the work against elastic recoil in elastic tissues, the work of expiration is completely transferred to expiratory muscles). Work against elastic recoil increases with slow and deep breathing, whereas work against airway resistance increases with rapid shallow breathing (i.e. where flow rates are increased). Patients with normal lung physiology who are at rest will trend toward a respiratory rate which is a compromise between these two competing sources of impedance, and which minimizes the work of breathing.
With normal quiet breathing the total oxygen consumption of the respiratory muscles is approximately 1 mL per liter of minute volume or 2% of the total body oxygen consumption.31 When the minute volume increases to 10 L/min in the absence of lung pathology, the oxygen cost of work of breathing accounts for 5% of total body oxygen consumption. In disease states which affect pulmonary compliance or airway resistance the oxygen cost of breathing can increase markedly. In COPD patients with poor lung function, the oxygen cost of the work of breathing at rest has been found to be in excess of 16 mL/L, or up to 50% of the total body oxygen consumption.41 Mechanical ventilation can significantly decrease the demands on a failing heart by assuming some or all of the respiratory workload.
The work of breathing can be measured by integrating the area under the pressure/volume diagram of a breath, where the measured pressure is the pleural pressure or next most convenient surrogate, e.g. esophageal pressure as measured by esophageal manometry.42 Measurement of pleural pressure and esophageal manometry are not often available at the bedside, but the pressure and volume graphics of a mechanical ventilator are effective surrogate measures for ventilated patients on volume control mode of ventilation with a constant inspiratory gas flow.43 During a mechanical breath a patient may perform part of the work of breathing, with the remainder being performed by the ventilator device. It is possible to calculate the level of ventilator dependence by comparing the work of breathing required for unsupported breaths and assisted breaths.
  • The respiratory tract consists of conductive (upper airway trachea and bronchi) and respiratory portions (respiratory bronchioles and alveoli), of which only the latter participate in gas exchange.
  • The roles of the upper airway include humidification and heating of inspired gas, protection of the lower airway from foreign material, phonation, swallowing, immune defence, and the maintenance of low resistance to air flow.
  • The gas exchange surface of the lower respiratory tract is made up of alveolar epithelial cells (Type I cells) and Type II cells which differentiate into Type I cells and secrete alveolar surfactant.15
  • Alveolar surfactant is a surface-active material, which is responsible for maintaining the low surface tension of alveolar fluid and thereby preventing alveolar atelectasis.
  • The pulmonary circulation is a low-resistance system, where the pressure is 15–20% of the systemic pressure and the vessels have significantly less smooth muscle.
  • The relationships of pressure volume and flow describe the mechanical properties of the respiratory system, such that compliance is the change in volume per unit pressure and resistance is the change in pressure per unit flow.
  • The relationship of compliance and resistance describe the time constant (τ), defined as the time required to distend the lung up to 63% of the maximal inflation.
  • The work of breathing is the energy required to generate a tidal volume, and can expressed in joules per liter of breath volume, or as power of breathing in Joules per minute.
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