IAP Recent Advances in Pediatrics P Ramachandran, Alok Gupta, Piyush Gupta, PSN Menon
INDEX
Page numbers followed by b refer to box, f refer to figure, fc refer to flowchart, and t refer to table.
A
Abatacept 299, 325, 334
Abdomen 474
ultrasonography of 466
Abdominal catastrophe 47
Abdominal distension 218
massive 465
Abdominal mass 464
palpable 464
Abdominal pain 464
Acanthosis 284
Accredited social
health activists 494
work activists 495
Acetaminophen 290
Acid base homeostasis, mechanisms of 250f
Acute respiratory distress syndrome 44
Acute-onset neuropsychiatric syndrome 146
Adalimumab 325, 327
Adenoma 318
secretory 318
Adenosine 176, 178
deaminase 290, 350
Adenotonsillar hypertrophy 364
Adenotonsillectomy 367, 371
Adenovirus 47
Adequate nutrition 384
Adrenal adenoma 318
Adrenal insufficiency 3, 197, 278
Agalsidase alpha 351
Agalsidase beta 351
Aggressive behavior 29
Airway 90
clearance therapy 201
colonization 200
management 428
Alanine aminotransferase 208, 231, 325
Aldosterone 318
Alemtuzumab 299
Alglucosidase alpha 351
Alkaline phosphatase 319
Allergic bronchopulmonary aspergillosis 194, 205
Alphacoronavirus 41
Alpha-fetoprotein 307310
Alphaviruses 103
Amino acid formula 220, 223
Aminoaciduria 245, 259
Aminocaproic acid 206
Amiodarone 178
Amphotericin B
colloidal dispersion 59, 73
deoxycholate 56, 59, 73, 74
dosing of 75t
lipid
complex 76
formulations of 74
preparations 74
Anakinra 332
adverse effects of 332
Anaphylactic reactions 29
Anaphylaxis 217, 223
Androgens 318
Anemia 291
pernicious 278
Anganwadi workers 494, 495
Angelman syndrome 344
Angioedema 223
Angiotensin-converting enzyme 101, 147
Anidulafungin 59
Anorexia 45
Anti-B cell antibody 333
Antibiotic choices 91
Antibiotic therapy 203
Antibody
neutralizing 108
test 48
Anticardiolipin antibody 327
Antiepileptic drug 450
Antifungal
agents 59
susceptibility 60t
therapy, history of 56
Antigen presenting cell 44, 334
Antihuman trafficking units 490
Anti-neutrophil cytoplasmic antibody 147, 325, 333
Anti-N-methyl-D-aspartate receptor encephalitis 142, 144b
Antinuclear antibody 147, 290, 301, 327
Antiphospholipid antibody syndrome 290, 300, 325, 333
Anti-rheumatic drugs, disease-modifying 324
Antisense oligonucleotides 355, 357
Antistreptolysin-O 147
Antithymocyte globulin 296
Anti-thyroid peroxidase 277
Anti-TNF therapy 328
Antituberculous therapy 329, 330
Antiviral agents 50
Aortic aneurysm dissection 29
Apnea
central 369
mixed 369
Appendiceal mucocele 463
Appendicitis 47
acute 468
Apremilast 337
Arginine vasopressin 257f
Arrhythmia 29, 49, 177, 179
Arterial blood pressure 450
Arthritis 93
enthesitis-related 325
Ascitic fluid 307
Asfotase alpha 351
Aspartate aminotransferase 70, 208, 232, 325
Aspartate transaminase 295
Aspergillosis 58
Aspergillus fumigatus 205
Asphyxia 3
AstraZeneca vaccine 107, 108t
Ataxia 252
telangiectasia 309, 310
Atopic dermatitis 197
Atopy, severe 218
Atrial flutter 172, 177
Atrial tachycardia 177
Attention deficit hyperactivity disorder 26, 29, 400
Auditory brainstem responses 423
Auditory hazards 417
Autism spectrum disorders 346
Autoantibody, absence of 284
Autoimmune
cerebellar syndrome 141
diseases 290
encephalitis 138, 139, 140b, 141t, 142t, 147, 147f, 152f, 154, 155, 157
hepatitis 290
limbic encephalitis 144
lymphoproliferative syndrome 290, 291, 300
panel 455b
Autoimmune hemolytic anemia 289, 290, 292, 295, 295fc, 297, 297fc, 298, 305
classification of 289t
mixed 305
secondary 296
Automatic arrhythmias 177
Autonomic dysfunction 144
Autosomal dominant 344
Autosomal recessive 344
multisystem disorder 190
Auxiliary nurse midwives 494
Azathioprine 299, 337
Azithromycin therapy, long-term 204
Azole 62
drugs
dosing of 66t
properties of 64t
B
Baby-friendly hospital initiative 501
Bacterial colonization, eradication therapies for 204
Bacterial infections 146
Bacterial meningitis 88t
Baricitinib 336
Barium contrast enema 466
Bartter and Gitelman syndromes, treatment of 255
Bartter syndrome 254f, 255, 260
Basal bolus regimen 268
Beckwith-Wiedemann syndrome 344
Behavior audiometry evaluation 423
Behavioral change theories 401
Behçet's disease 337
Behçet's syndrome 332
Belimumab 334
Benzodiazepines 156, 444, 447
Betacoronavirus 41
Beta-D-glucan 57, 58
Beta-thalassemia 344
Bicarbonate 243
Bicarbonaturia 245
Bickerstaff encephalitis 141
Biliary obstruction 309
Biosimilars 337
Biotinidase levels 164
Birth asphyxia, severe 14
Bladder tumor 29
Blood 307
cultures 87
gas analysis 7
glucose 270, 271
control, targets of 275t
premeal 270b
self-monitoring of 269, 272, 275
in stools 464
investigations 465
pressure 2, 5, 5t, 9, 11
normal 247
tests 150
transfusion 298
Blood-brain barrier 81
Bloody mucus per rectum, passage of 464
Body mass index 25, 230, 236
Body surface area 428
Bonded labor 489
Bonded Labor System Act 492
Bone
alkaline phosphatase 317
mineralization, defective 27
tumor 316
angiogenesis markers 317
Bradycardia 173f
Brain 2
deep 456
development 393
injury, traumatic 446
magnetic resonance imaging of 145, 164
malformation, congenital 446
positron emission tomography 150
tissue staining 148
tumors 29
Brainstem
auditory evoked response 423
encephalitis 141
Breathing 90
exercises 202
Bronchoalveolar lavage 47, 58, 59
Brugada syndrome 183, 184f, 185
Bruises 480
Bull's eye sign 466
Burkholderia cepacia 195
Burn 428, 430, 438, 481
chemical 430
electrical 430
hypermetabolic phase after 439
injuries, types of 430
management of 428
patient, care of 434
specific pain anxiety scale monitors pain 436
surface area calculation 429f
transfusion in 438
wound
assessment 435
care, advances in 435
C
Calcipenic rickets 258
Calcium 243, 450
Canakinumab 333
Candida cystitis 76
Candidiasis 58
Cannabinoids 457
Capillary refill time 2, 11
delayed 5
Carbohydrate
antigen 308, 312
higher consumption of 26
Carbon dioxide monitoring 368
Carcinoembryonic antigen 308, 317
Carcinoid syndrome, symptoms of 316
Carcinoid tumors 316, 318
Carcinoma 318
Cardiac arrhythmias 169, 181f
common 171, 177t
Cardiac output 8
Cardiac resynchronization therapy 181
Cardiac systolic functions, assessment of 8
Cardiology 169
Cardiometabolic biomarkers 29
abnormal 25
Cardiomyopathy 29
Cardiopulmonary resuscitation 446
Cardiovascular disorders 419, 420
Cardiovascular dysfunction 6
Caspofungin 59, 72
Castleman disease 300
Catecholamine
catabolism 314f
role of 313, 315
Catecholaminergic polymorphic ventricular tachycardia 183, 185
Catechol-o-methyl transferase 314
Celiac disease 218, 277, 463
Central nervous system 70, 71, 83, 146, 351
infections 86, 443, 446
manifestations 27
Central venous
access 9
pressure 8, 9, 90, 450
Cephalosporins 290
Cerebellitis 141
Cerebral edema 29
Cerebral vasospasm 29
Cerebral venous sinus thrombosis 110
Cerebrospinal fluid 7, 10, 58, 65, 79, 88, 88f, 93, 140, 144, 145, 147, 164, 307, 455
analysis 148
Cerliponase alpha 351
Certolizumab pegol 328
Chaperone therapy 358
Chemiluminescence enzyme immunoassays 48
Chemoprophylaxis 94
Chest
hyperinflation 193
physiotherapy 202
Child abuse 479
Child and Adolescent Labor (Prohibition and Regulation) Act 492
Child labor
and exploitation 488
consequences of 491
prevention of 491
rehabilitation of 492
Child neglect 477, 478
Child Protection Committees 494
Child protection mechanisms 493
Child rights 477
Child sex workers 489
Child sexual abuse 482, 485b
diagnosis of 483
management of 482
prevention of 486
Child trafficking 490
Chloride 243
channel, calcium-dependent 191
Chlorpromazine 314
Chocolate agar culture plates 87f
Cholesterol ester storage disease 230
Choriocarcinoma 307, 312
Chromaffin tumors 315
Chromosomal breakage 29
Chromosomal disorders 343
Chromosomal microarray 345, 346, 347f
Ciprofloxacin 95, 203
Cirrhosis 309
Citrin deficiency 230
Citrullinemia 309
Claw sign 467
appearance 467f
Clotrimazole 62
Coagulation disorders 93
Coagulopathy 45
Coccidioides immitis 63
Cognitive impairment 419, 420
Coiled spring sign 467
Cold agglutinin disease 301
Cold agglutinin syndrome 301, 302, 302f
pathophysiology of 302
treatment of 303
Colitis 309
Combination therapy 153
Common tubular disorders, causes of 246
Communication 35
Comparative genomic hybridization 345, 345f, 346
Complete blood count 7, 48, 89, 290, 297, 302, 325, 450
Congestive cardiac failure 291
Conn syndrome 318
Consciousness, altered 218
Continuous glucose monitoring system 269, 272, 276, 285
Continuous subcutaneous insulin infusion 271
Coombs test 296b
direct 289, 294, 295
false positive direct 295
Coronary thrombosis, acute 29
Coronary vasospasm 29
Coronavirus disease-2019 (COVID-19) 40, 41, 45, 46fc, 52, 52fc, 101, 104, 105, 111, 118, 118t, 119t, 331
epidemic 53
infection 44, 49, 111, 121
phases of 43f
pandemic 40, 332, 396, 405
pathogenesis of 43
pneumonia 48, 49, 50, 53
prevention of 107
signs of 46
structure of 42f
symptoms of 46
types of 40f
vaccine 102, 103, 106, 120, 121, 126
effectiveness of 127
equitable distribution of 120
inactivated 106
prioritization of 121
rapid development of 102
second-generation 129
Cortical dysplasia 145
Cortisol 318
Costimulatory pathway, inhibition of 334
Cotrimoxazole 203
Cough, chronic 193
Covaxin 106
Cow's milk 219
protein allergy 215, 216, 218, 218b, 219t, 221fc, 223, 226
diagnosis of 215
related symptom score 219
C-reactive protein 48, 52, 89
Creatine kinase-muscle brain 10
Creatinine phosphokinase 451
Crepitations 193
Criminal Law (Amendment) Act 492
Critical care 428, 442
pain observation tool 436
Cryopyrin-associated periodic syndrome 332
Cryptococcal meningitis 76
Cryptococcosis 58
Cryptococcus neoformans 62
Curreri junior formula 437, 438t
Cushing's syndrome 318
Cutaneous microflora 500
Cyclic adenosine monophosphate 337
Cyclophosphamide 155, 299
Cyclosporin 299
Cystic fibrosis 190, 193t, 194, 194t, 196fc, 344, 463
diagnosis of 196
newborn screening 198
nutritional management of 206
Cysts, duplication 463
Cytomegalovirus 47, 146, 290, 300
D
Daily sleep duration 398
Deafness 193
Dehydration 193, 208
Dehydroepiandrosterone 233
Delinquency 29
Delta variant 125
Deltacoronavirus 41
Demyelinating diseases 141
Dendritic cells 43, 44
Dengue 46, 86
fever 46
Dent disease 245, 246, 252, 260
Dental erosions 27, 29
Deoxyribonucleic acid 344, 345
antibodies 290
Depression 29
Dermatology 499
Dermatophytes 57
Dermis 499
Dexamethasone 255
Diabetes
center, monitoring at 276
Control and Complications Trial 265
education 282
insipidus 91, 258f
Diabetes mellitus 264, 266f, 284
clinical features of 264
cystic fibrosis related 208
diagnosis of 265, 265b
management of 264, 265
neonatal 284
type 1 264, 285
Diabetic ketoacidosis 47, 264, 269
Diaper care 503
Diarrhea 45, 464
persistent 218
watery 318
Diastolic functions, assessment of 8
Differential lymphocyte count 48
Digoxin 178
Dihydroxyphenylacetic acid 314
Disasters, neglect during 479
Disseminated intravascular coagulation 16
Distal intestinal obstruction syndrome 195, 205
Dobutamine 13
Donath Landsteiner antibody 304
Dopamine 13, 313
Doughnut sign 466
Down syndrome 231
Drowning 446
Drug interactions 72
Drug therapy 185
Dry powder inhalation 202
Duchenne muscular dystrophy 314, 344, 356
Dysgerminoma 312
Dyslipidemia 29
E
Early learning
opportunities for 385
promote 389
Early multiple organ dysfunction syndrome 46
Eating disorders 400
Echinocandins 62, 72
Echocardiography 49
Eczema 218
Elafibranor 238
Eleclazine 186
Electroconvulsive therapy 457
Electroencephalogram 144, 147, 150, 161, 165, 368
Electrolyte imbalances 446
Electromyogram 368
Electroretinogram 166
Elevated beta-human chorionic gonadotropin, causes of 312t
Elevated urine catecholamine metabolites, causes of 314b
Elexacaftor 209
Embryonal carcinoma 312
Emollients, classification of 505b
Empyema 193
Encephalitis 446
causes of 138
Encephalomyelitis, acute disseminated 156
Encephalopathy, acute necrotizing 146
Endocarditis, infective 86
Endocrinology 264
Endothelial damage 93
Enema, delayed repeat 468, 471
Energy drinks 29
banning of 32
harmful effects of 26
reduce consumption of 31
Energy-dense low-nutrient density foods 20
Enteric fever 47
Enterocolitis syndrome, food protein-induced 216218
Enteroviruses 8, 47
Environment protection agency 417
Environmental noise pollution 425
health hazards of 416, 416t
Enzyme phenylethanolamine-N-methyltransferase, lack of 313
Enzyme replacement therapy 350, 351, 351t
principle of 350
Enzyme-linked immunosorbent assay 48, 109, 148, 290, 294
Eosinophilic gastrointestinal syndromes 218
Epilepsy 141, 252, 442, 445
surgery 457
syndrome 161
febrile infection-related 454
Epileptic spasms 161, 163, 166
Epinephrine 13, 15
Epithelial autografts, cultured 436
Epithelial sodium channels 191
Epstein-Barr virus 47, 146, 290, 300, 302
Erythrocyte sedimentation rate 48, 93, 327
Erythromycin 290
Escherichia coli 88
Estrogens 318
Etanercept 325, 326
Eteplirsen, mechanism of action of 356f
Etripamil 176
European Medicines Agency 354
Evans syndrome 290, 299, 300b
treatment of 301
Exome sequencing 348
Extensively hydrolyzed formula 220, 222
Extracorporeal membrane oxygenation 11, 15, 49
Eye
congestion 47
problems 401
F
Fabry disease 351
Failure to thrive 193, 217, 218
Falling sickness 442
Familial polyposis 463
Family planning 491
Family welfare 491
Fanconi anemia 309, 311
Fanconi syndrome 243
Fanconi-Bickel syndrome 252
Fast food 19
in schools, regulation on consumption of 28
Fatigue 291
Fats, higher consumption of 26
Fatty liver indicator, ultrasonography 236
Feminization 318
Fetomaternal bleed 3
Fever 46, 47
Fibrinogen 48
Fibroblast growth factor 260
Fibrosis score 234
Flecainide 178
Flowcytometry 148
Fluconazole 59, 62, 63, 64, 66, 71
Flucytosine 59, 62, 76
Fluid management 431
Fluid resuscitation 14, 90
Fluorescence in situ hybridization 343
Fluoroquinolone 203
Food 314
additive sensitivity 215
allergy 215
aversion 215
intolerance 215
labeling 23, 30
processing 21
ultra-processed 19
Food Safety and Standards Authority 21
Forensic evidence, collection of 484
Fractures 481
Fragile X syndrome 344
Fresh frozen plasma 15, 93
Frontline healthcare workers 121
Fungal infections 146
invasive 56
Fungi, classification of 57f
G
Galactomannan 59
Galactorrhea 318
Galactosemia 252
Galsulfase 351
Gamma-aminobutyric acid 443
receptors 444f
Gammacoronavirus 41
Gamma-glutamyl transferase 208, 236
Gangrene 93
Gastrin 318
Gastrinoma 318
Gastroenteritis 468
Gastroenterology 215
Gastrointestinal complications, management of 207
Gastrointestinal effects 83
Gastrointestinal losses 12
Gastrointestinal symptoms 45
Gastrointestinal tract 215
Gaucher disease 344, 351
Gene therapy 352
strategies 352fc
Genetic disorders
diagnosis of 343
treatment of 343
Genetic metabolic encephalopathies 146
Genome sequencing 348
Genotoxicity 29
Germ cell tumors 307, 310312
malignant 310
non-seminomatous 309
Germinoma, pure 312
Germline gene therapy 352
Gestational trophoblastic disease 312
Giant-cell hepatitis 300
Gibson and Cooke method 197
Giemsa stain 293f, 302f
Gigantism 318
Gitelman syndrome 254f
Glasgow coma scale 90
Glasgow meningococcal septicemia prognostic score 93, 94b
Glioma 145
Glucagon 318
Glucagonoma 318
Glucocorticoid 337
responsive circulatory collapse 14
Glucose-6-phosphate dehydrogenase 292
Glucosuria 245
Glutamate 443
Glutamic acid decarboxylase 138, 141
antibody 147
Glycemic control 439
monitoring of 274
Glycemic index 279
Glycine receptor 141
Glycogen storage disorder 197
Glycogenosis, hepatic forms of 230
Glycosylated hemoglobin 52, 265, 275
Glycosylation, congenital disorders of 230
Golimumab 328
Gram stain 88
Granulosa cell tumor 318
Graves’ disease 278
Growth 376
factor, insulin-like 317
failure 252
hormone 318, 438, 439
Guselkumab 335
H
H1N1 120
Haemophilus influenzae 88, 195
Haemorrhage 162
Hallucinations 29
Hayfork sign 466
Headache 29
Health care
infrastructure 494
professionals 484
Hearing
organs of 412, 412f
protectors, use of 424
surveillance 425
Hearing loss 29, 414, 415
classification of 415, 415b
diagnosis of noise-induced 423
etiology of 415
hidden 417
noise-induced 411, 415, 417, 423
treatment of noise-induced 423
types of 415
Heart 2
block, complete 173, 173f, 177
disease, congenital 10, 11, 179
electrical activity of 183
Heart rate 13
abnormalities 4
calculation of 170
Helicobacter pylori 300
Hemangioma 463
infantile 309
Hematology, pediatric 289
Hematopoietic stem cell transplant 299, 306
Hemodynamic monitoring, signs of 6
Hemodynamic status 428
Hemoglobinemia 292
Hemoglobinuria 292
Hemolytic-uremic syndrome 463
Hemophagocytic histiocytosis 146
Hemophagocytic lymphohistiocytosis 336
Hemophilia 463
Hemosiderinuria 292
Henoch-Schönlein purpura 463
Hepatic steatosis 231
Hepatic tumors 309, 312
Hepatitis
acute 309
C 290
virus 300
chronic 309
Hepatoblastoma 309, 318
Hepatocellular carcinoma 309
Hepatocellular malignant neoplasm 309
Hepatology 230
Hepatoma 318
Hereditary fructose intolerance 230
Hereditary nephrogenic diabetes insipidus 197
Hereditary spherocytosis 292
Hereditary tyrosinemia 310
Herpes simplex
encephalitis 141, 157
virus 8, 139, 146
Herpes viruses 103
Heterozygosity, loss of 346
Histocompatibility complex, major 334
Holter evaluation 174
Homovanillic acid 313
Hormonal tumor 318
markers 318t
Hormone 308, 317
adrenocorticotropic 13, 165
antidiuretic 255
artificial pancreas, dual 274
follicle stimulating 311
high parathyroid 259
intramuscular adrenocorticotropic 164
luteinizing 311
parathyroid 259f, 318
serum thyroid stimulating 232
thyroid 317
thyroid-stimulating 277, 311
Human chorionic gonadotropin 311
beta fraction of 307, 311
Human coronaviruses 43
Human embryonic kidney 148
Human herpes virus 146
Human immunodeficiency virus 86, 146, 231, 290, 291, 300
infection 353
Human papillomavirus vaccine 338
Hutchinson maneuver, modified 472
Hybrid-closed loop pump 273
Hydrocortisone 16
Hydrolyzed formula 224
partially 224
Hydrostatic enema reduction 470
Hydrostatic reduction 468
Hydroxyindolacetic acid 316
Hyperactivity 29
Hyperaldosteronism 255
Hypercalciuria 248, 252
chronic 255
Hyperchloremic metabolic acidosis 244246
Hyperekplexia 163
Hyperglycemia 318
history of 284
Hyperkalemia 245, 248
Hypermetabolism 438
Hypernatremia 91
Hyperparathyroidism 260
Hypersensitivity 29
reaction 274
Hypertension 25, 29, 144, 247, 248, 318
monogenic disorders of 253
Hyperthermia 144
Hyperthyroidism 260, 318
Hypertonic saline 201
Hypoallergenic formula 224
Hypocalcemia 91
severe 259
Hypoglycemia 7, 280, 281, 284, 318, 446
management of 280fc
severe 281
Hypokalemia 91, 244246, 252, 318
chronic 255
Hypokalemic metabolic alkalosis 247
Hypomagnesemia 91, 248, 255, 260
Hyponatremia 91, 248, 446
Hypophosphatasia 351
Hypophosphatemia 91
Hypophosphatemic rickets 259
Hypopnea 368, 369
Hypotension 2, 4, 6, 16, 29, 218, 446
catecholamine-resistant 15
Hypothalamic diseases 231
Hypothermia 218, 456
Hypothyroidism 197, 231
Hypoventilation, sleep-related 369
Hypovolemia 3, 83
Hypoxia 45, 49, 54, 446
Hypoxic ischemic
encephalopathy 162
insult, acute 446
Hypsarrhythmia 164
I
Ibuprofen 290
Idiopathic thrombocytopenic purpura 463
Idursulfase
alpha 351
beta 351
Imidazoles 62
Imiglucerase 351
Immune
deficiency 218
hemolytic anemia, drug-induced 296
mediated disorders 146
responses, cell-mediated 105
Immunizations 101
Immunodeficiency
common variable 290, 300
disorders 290, 300
severe combined 300
Immunoglobulin
G 289
intravenous 52, 59, 93, 153, 296, 298, 299
M 289
profile 290
Immunohistochemistry 86
Immunomodulation 50
Immunoreactive trypsinogen 198
Immunotherapy 455b
Implantable cardiac devices 181
Implantable cardioverter-defibrillators 181
Incontinentia pigmenti 344
Indigenous sweat collection system 197f
Infantile spams
diagnosis of 163
etiology of 163
pathogenesis of 161
Infection, chronic 296
Infectious bronchitis virus 40
Infectious diseases 40, 56, 79
Inflammatory disorders 146
Inflammatory inhaled nasal steroids 372
Infliximab 325, 327
Influenza vaccination 338
Inhalational injury 431
Inherited arrhythmias 183, 185
Inherited disorders 446
Insulin 318
adverse effects of 274
carbohydrate ratio 270b
conventional 267
delivery, modes of 271
dosing 269
edema 274
inhaled 284
injection technique 269
neuritis 274
newer 267
pump 271273
advantages of 273
set 271f
regimen 268
requirement, low 284
sensitivity factor 270b
therapy 266
principles of 268
types of 267t
Insulinoma 318
Integrated Child Development Services 391, 494
Integrated Child Protection Scheme 494
Intellectual disability 346
Intensive care units 50, 54, 122
Interferon gamma release assay 328, 329
Interferon genes, stimulators of 336
Interleukin inhibitors 331, 330, 335
International League Against Epilepsy Task Force 444
International Society of Pediatric and Adolescent Diabetes 278
Intestinal polyps 463
Intoxication 446
Intracranial tension 29
raised 83, 92
Intussusception 460, 460f, 473f, 475
pathophysiology of 462f
transanal protrusion of 465f, 468
Invasive meningococcal disease 79, 85, 86
prevention of 94
prognosis of 93
Iron overload 292
Irritability 29
Isavuconazole 59, 62, 63, 65, 70, 72
Isosexual precocity 318
Isseminated intravascular coagulation 93
Itraconazole 59, 6264, 67, 71
Ivabradine 177
Ivacaftor 209
Ixekizumab 335
J
Janus kinase 52
signal transduction 335
Jaundice 291, 292
Junctional ectopic tachycardia, congenital 177
Junk food 19, 20
harmful effects of 25
reduce consumption of 28
Juvenile dermatomyositis 325, 331, 333
Juvenile idiopathic arthritis 290, 325
pathogenesis of 324
systemic-onset 330
Juvenile Justice (Care and Protection) Act 492
K
Kawasaki disease 46, 122, 325
Ketamine 437, 453
Ketoconazole 62
Ketogenic diet 454
Ketone testing 276
Klinefelter syndrome 284
L
Lacosamide 455
Lactate dehydrogenase 292, 297, 308, 317
Lactose intolerance 215, 218, 219t
Langerhans cells 499
Language dysfunction 143
Laparoscopy 473
Laparotomy 472
Laronidase 351
Latex agglutination test 87
Law on Child Sexual Abuse 487
L-dopa 314
Leber congenital amaurosis 353
Left atrial pressure 9
Lens culinaris hemagglutinin 308
Leptospirosis 46, 47, 86
Lethargy 218, 464
Leucine-rich glioma inactivated protein 141
Leukemia 300, 463
acute 290
Leukodystrophy 148
Leukoencephalopathy, acute 146
Leukomalacia, periventricular 162
Levofloxacin 203
Levosimendan 13
Leydig cell tumor 318
Liddle syndrome 254, 255
Limb
ischemia 93
thick ascending 244
Limbic encephalitis 141
Lipid complex amphotericin B 59
Lipodystrophy 274
Lipoma 463
Lipo-oligosaccharide 82
Lipoprotein cholesterol
high-density 25, 29
low-density 25, 29
Liposomal amphotericin 59, 76
Liquid chromatography, high-performance 313
Live attenuated vaccines 103
Liver
biopsy 234
damage, drug-induced 309
disease 296
cystic fibrosis related 207
disorders, benign 309
fibrosis, enhanced 232, 236
function test 236, 327, 450
Loop of Henle 253f
Low birth weight 378, 379
extremely 3, 11
Low molecular weight
heparin 43
proteinuria 245
Lowe syndrome 243, 252
Lumacaftor 209
Lumbar puncture 87
Lund-Browder chart 429t
Lung injury, transfusion-associated acute 438
Lyme disease 86
Lymphangioma 463
Lymphocyte subset analysis 290
Lymphoma 29, 300, 463
Lysosomal acid lipase deficiency 351
Lysosomal storage disorders 349, 350
M
Macrophage activation syndrome 332
Macrovascular disease 278
Magnesium 243, 450
fractional excretion of 262
Magnetic stimulation therapy 456
Maintenance therapy 155
Malabsorption 193
Malformations 162
Malnutrition 197
severe 193
Marfan syndrome 344
Mass palpable per rectum 465
Maternal mental health, support 389
Matrix metalloproteinases 332
Maturity-onset diabetes of young 284
Mean arterial pressure 5, 11
Mean corpuscular volume 302
Measles virus 103
Mechanical ventilation 49
Meckel's diverticulum 463
Meconium ileus 193, 207
equivalent 193, 207
Medical nutrition therapy 278
Medical therapy 372
Medicines and Healthcare Products Regulatory Agency 110
Medicolegal case 483
Medullary nephrocalcinosis 252
Medullary thyroid carcinoma 318
Melanocytes 499
Meningitis 84, 446
belt 80
Meningococcal
disease 79, 80, 95t
meningitis 84, 86
septicemia 84, 86
Meningococcemia 84, 85f
Mental health support 485
Mercuric nitrate 197f
Mesenchymal hamartoma 309
Metabolic abnormality 208
correction of 91
Metabolic acidosis 91
Metabolic alkalosis 195, 252, 254fc
Metabolic disease 230, 446
Metabolic disorders 148
Metabolic effects 25
Metabolism, inborn error of 349, 446
Metabotropic glutamate receptor 141
Metadrenaline, free 316
Metalloproteinase, tissue inhibitor of 234
Metered dose inhaler 201
Methotrexate 337
Methylprednisolone 299
Mexiletine 185
Micafungin 59, 73
Miconazole 62
Microangiopathic hemolytic anemia 292
Microneutralization test 123
Microsporum 57
Microvascular injury 82
Midazolam 451
Middle east respiratory syndrome 40
Milrinone 13
Minimal nutritional value, foods of 20
Mitochondrial inheritance 344
Mixed venous oxygen saturation 8
Modern slavery 489
Molnupiravir 53
Monoamine oxidase 314
Monoclonal antibodies 51
Monogenic disorders 343, 347, 354t
Motor neuron, survival of 356
Movement disorder 141, 143
Mucopolysaccharidosis 197, 350, 351
Mucormycosis 58
Multifactorial disorders 343
Multifocal leukoencephalopathy, progressive 325
Multiple daily injections 268
Multiple food allergies 218
Multiple sclerosis 325
Multisystem inflammatory syndrome 46, 52, 332
Muscle activity increase 446
Mutation analysis 197
Mycophenolate mofetil 299
Mycoplasma
pneumonia 290, 300, 302
infection 303
serology 290
Myelin oligodendrocyte glycoprotein 141, 147
antibody 147
Myelodysplasia 300
Myelodysplastic syndrome 290
Myeloid leukemia, chronic 290
Myoclonic epilepsy, progressive 446
Myopericarditis 113
Myotonic dystrophy 344
N
Nasal oxygen, high-flow 49
Nasal polyposis 193
Nasal potential difference 196, 198
Nasal swabs 47
Nasogastric suction 472
Nasogastric tube 207
National Centre for Disease Control 96
National Charter for Children 477
National Early Childhood Care and Education 391
National Glycohemoglobin Standardization Program 265
National Health and Nutrition Examination Survey 415
National Institute for Health and Clinical Excellence 90, 501
National Institute of Health 21, 102
National Nutrition Policy 391
National Plan of Action for Children 391
National Policy for Children 477
National Policy for Education 391
National Regulatory Agencies 106
National Regulatory Authority 106
Nausea 45
Near infrared spectroscopy 8
Neisseria meningitides, colonies of 87f
Neisseria meningitidis 79
Neonatal intensive care units 1
Neonatal Resuscitation Program 11
Neonatal skin condition score 505, 506b
Neonatology 1
Neoplasm 148
Neoplastic disorders 146
Neoplastic tissue, proteins produced by 308
Nephritis 290
Nephrocalcinosis 248, 260
evaluation for 261b
Nephrogenic diabetes insipidus 257f
Nephrolithiasis 248, 260
evaluation for 261b
Nephrology 243
Nephronophthisis 255
Nephropathy 278
Neuroblastoma 307, 313, 318
Neurofibromatosis 344
Neurogenic tumors 316
Neurologic signs 6
Neurology 138, 161
Neuromyelitis optica spectrum disorders 147
Neuron-specific enolase 313, 315
Neuropathy 278
Neuroplasticity 376
Neuropsychiatric symptoms 141
Neurosecretory proteins 315
Neutropenia 331
Neutrophil ratio 7
Newborn, massage of 502
Next generation sequencing 348
Nirmatrelvir 51
Nitric oxide, inhaled 13
N-methyl-d-aspartate 444
receptor 138, 141, 144
antibodies 147
Noise 414
annoyance 419
harmful effects of 424
monitoring 424
pollution 421
areas of 416
sensitivity 419
sources of 416
Nonaccidental injuries 480
Nonalcoholic fatty liver disease 230, 236
clinical diagnosis of 231
diagnosis of 231
metabolic signature of 233
microbiome signature of 233
Nonalcoholic steatohepatitis 230, 231
Non-auditory hazards 418
Non-Hodgkin lymphoma 290
Noninvasive management 373
Noninvasive ventilation 49
Nonrespiratory therapy 206
Nonsteroidal anti-inflammatory drugs 437
Noradrenaline 13
Norepinephrine 313
Normetadrenaline, free 316
Nucleic acid
amplification testing 47, 53, 108
vaccines 104
Nucleocapsid protein 124
Numerous gastrointestinal pathogens 461
Nurturing care framework 381, 393
Nusinersen, mechanism of action of 356f
Nutrient profiling 23
Nutrition 19, 437
O
Obesity 29, 284, 400
Obeticholic acid 238
Obstructed sleep disordered breathing, spectrum of 363f
Obstructive apnea 369
hypopnea index 369
score 370t
Obstructive sleep apnea 361, 364
Ofloxacin 203
Oligodendrocyte glycoprotein 138
Oliguria 83
Omicron variant 51, 126
emergence of 51
Omphalitis 504
Oncology 307
Opsoclonus myoclonus syndrome 141
Oral food challenge 220, 222
test 215
Oral glucose tolerance test 209, 265
Oral rehydrating solution 208, 432
Oropharyngeal swab 47
Osteoporosis 29
Otoacoustic emissions 423
Otorhinolaryngology 361
Ovarian teratoma 150
Oximetry score 367
Oxygen 49
saturations 367
P
Packed cell volume 11
Pain 464
management 436
relief, paracetamol for 430
Pancreas, artificial 273
Pancreatic enzyme replacement therapy 206
Pancreatitis 47
Pandemic speed vaccines 102
Paracetamol 314, 437
Paraganglioma 315
Parathyroid hyperplasia 318
Paroxysmal cold hemoglobinuria 292, 295, 304
treatment of 304
Paroxysmal supraventricular tachycardia 172, 176178
Partial thromboplastin time 48
Parvovirus B19 290, 300
Patent ductus arteriosus 2, 3, 14
Pathogen-associated molecular patterns 104
Pediatric arrhythmias, pharmacologic therapy of 176
Pediatric autoimmune
encephalitis 146t
neuropsychiatric disorders 146
Pediatric cardiac arrhythmias, diagnosis of 169
Pediatric emergency departments 169
Pediatric intensive care unit 430, 434, 434t, 450
Pediatric multisystem inflammatory syndrome 46
Pediatric nonalcoholic fatty liver disease
fibrosis index 234, 236
histological score 235
Pediatric surgery 460
Penicillins 290
Perinatal hypoxic-ischemic injury 446
Personal audio device 415, 418
Peutz-Jeghers syndrome 463
Peyer's patches 462
pH 243
Phenobarbitone, high-dose 453
Pheochromocytoma 315, 318
Phosphate 243
Phosphaturia 245
Phosphodiesterase inhibitors 337
Phosphorus 450
Physical violence 479
Physician's responsibility 485
Piperacillin 290
Plaque reduction neutralization test 123, 123t
Plasma
catecholamines 313
exchange 153
glucose 265
Plasmapheresis 153
Plasminogen activator inhibitor 83, 238
Pneumatic enema reduction 469
Pneumatic reduction 468
Pneumococcal vaccination 338
Pneumocystis jirovecii 57
infection 155
Pneumonia 44, 45
persistent 193
Pneumoperitoneum 465
Pneumothorax 193, 206
Poisoning 446
Polyamines, free 317
Polychromatic cells 293f
Polyenes 62, 73
Polymerase chain reaction 57, 58
tests 8
Polymorphic ventricular tachycardia 185f
Polysomnogram 365
Polysomnography 365
Polysymptomatic encephalopathy 141
Polyuria 248, 255, 256
Pompe disease 350, 351
Posaconazole 59, 62, 63, 65, 69, 71
Positive airway pressure 370
therapy 372
Positive expiratory pressure 202
devices 202
Post-infectious encephalopathy 146
Poststatus epilepticus 145
Post-stem cell transplantation 300
Post-traumatic stress disorder 485
Potassium 243
Poxviruses 103
Prader-Willi syndrome 344, 362
Prandial insulin 270b
Precocious puberty 318
Prednisolone 299
Propofol 451
Propranolol 178
Prostaglandin 11
E1 11
Protection of Children from Sexual Offences Act 484, 487
Prothrombin time 48, 450
Prothromboplastin time, active 50
Proton
density fat fraction 235
pump inhibitors 65
secretion of 243
Proximal tubule 244
Pseudo-kidney 466
sign 467f
Pseudomonas 191, 203
aeruginosa 195, 204
infection 203
Psoriatic arthritis 325
Psychiatric disorders 146
Psychiatric disturbances 27
Psychological behaviour, abnormal 26
Psychological disorders 29, 401
Psychosocial aspects 283
Public education 424
Pulmonary complications 205
Pulmonary effects 83
Pulmonary exacerbations
management of 202
prevention of 204
Pulmonary hypertension, persistent 13, 14
Pulmonary involvement 45
Pulmonology 190
Pulse oximetry 366
Purpura fulminans 85f
Q
QRS complex 170
QT prolongation 29
QT syndrome, long 185
Quantitative fluorescence polymerase chain reaction 345
R
Radiofrequency ablation 179
Radioimmunoassay 148
Rag picking 489
Randomized control trial 50
Rapid antigen test 47, 53
Rapid maxillary expansion 371
Rash 46
Rashtriya Bal Surakhsha Karyakram 392
Reactions, systemic 218
Receptor-binding domain 101
Rectal prolapse 193, 468
Red blood cell 289
Red currant jelly stool 462
Red flag signs 218b
Refractory autoimmune hemolytic anemia 298
Refractory rickets 258
Relapses 156
Remdesivir 53
Renal carcinoma 318
Renal diseases 255
Renal disorders 296
Renal dysplasia 255
Renal impairment 83
Renal signs 6
Renal tubular
acidosis 244, 250f, 251, 259f
disorders 243
Respiratory effort-related arousal 369
Respiratory inductance plethysmography 368
Respiratory management 201
Respiratory signs 6
Responsive caregiving 386, 389
Resuscitation, endpoints of 432
Reticulocytopenia 295
Reticulocytosis 304
Retinopathy 278
Reverse transcription polymerase chain reaction 47, 52, 53
Rhesus 289
Rhesus-human reassortant rotavirus vaccine 461
Rheumatic disorders, pediatric 324, 325t
Rheumatoid arthritis 300
Rheumatological disorders 300
Rheumatology 324
Rhinosinusitis 362
Ribonucleic acid 355
aptamers 355
messenger 356, 357
small interfering 355
therapeutics 355
vaccines 104
Rice-based feeds 224
Rickettsiosis 86
Right iliac fossa, emptiness of 464
Right to Education Act 480
Rilonacept 333
Ringer's lactate 90
Risdiplam 358
Ritonavir 51
Rituximab 154, 155, 299, 303, 325, 333
Rotavirus 461
Rubella 290
Rule of Nines 429
Russell-Silver syndrome 344
Ruxolitinib 336
S
Salicylate 215
Salt craving 193
Salty taste 193
Sawtooth appearance 173f
Scalp, care of 504
Scarlet fever 46
Scleroderma 331
Sclerosing cholangitis, primary 290
Sclerosing panencephalitis, subacute 150
Scrub typhus 46
Sebelipase alpha 351
Secukinumab 335
Seizures 29, 92, 143, 155
Selonsertib 238
Seminoma 312
Sensor augmented pump 273
Sensorineural deafness 252
Sensorineural hearing loss 417
Sensorium, altered 29
Septicemia 84
Sertoli cell tumor 318
Sertoli-Leydig cell 318
tumors 309
Serum
and urinary catecholamines 307
creatine phosphokinase 232
sodium 243
uric acid 232
Severe acute respiratory distress syndrome 40, 101
Severe acute respiratory syndrome-related coronavirus
infection 40, 45
structure 42f
vaccine 101, 112
variants 125f
Sexual abuse 483
Sexually transmitted disease 484
Shields technique 469
Shigella dysentery 218
Shock 1, 2, 4, 7, 14, 47, 84, 89
compensated 9
in transitional circulation 12
neonatal 1, 9t, 10t
pathophysiology of neonatal 3t
septic 3, 6, 14, 47
septicemia with 86
septicemia without 83
time sensitive management of 11fc
types of 10
Shunts, intracardiac 3
Sick day management
education 283
guidelines 283b
Sigmoidoscopy 220
Signe-de-dance sign 464
Single nucleotide polymorphism 345, 346
chromosomal microarray 346f
Sinus
bradycardia 173
rhythm 171
Sinusitis, recurrent 193
Sirolimus 299
Skin
care 499, 506
neonatal 501
cleansing, neonatal 502
composition 500
function 500
prick test 219
rashes 193
structure 500
Sleep 400
disordered breathing 361
disturbance 143
and insomnia 419
endoscopy, drug-induced 370
pattern, disturbed 29
Small bowel intussusceptions 465
Small molecule therapy 358
Snorers, primary 363
Social cognitive theory 401
Sodium
and chloride ions, absorption of 253f
bicarbonate cotransporter 250
channels, voltage-gated 455
Somatic gene therapy 352
Sotalol 178
Sotrovimab 51
Sound 411
assessment of 411
frequencies 413
Soy protein formula 224
Spasms, infantile 161, 162, 166
Spirometry 200
Splenectomy 299
Split mix regimen 268
Sporothrix schenckii 74
Sputnik light 114
Staphylococcus 191
aureus 195, 205
Status epilepticus 141, 445, 450, 457
febrile infection-related 146
generalized 442
management of 442
nonconvulsive 443, 451
refractory 143, 442, 445, 450, 454
super-refractory 445, 450
Steatohepatitis 231
Stem cell transplant 58
Steroids 15, 49, 92, 153, 469
inhaled 202
Stratum corneum 499
Street children 489
Streptococcal infections 146
Streptococcus pneumoniae 88
Streptomyces nodosus 73
Stroke 29, 148, 162
Substrate reduction therapy 358
Subunit vaccines 104
Sudden cardiac death 29
Sudden infant death syndrome 184
Sugar-sweetened beverages 30
Suicidal tendencies 29
Supraventricular tachycardia 175f
Sweat chloride estimation 196
Symptomatic disease 130
Symptomatic status epilepticus, acute 446
Syndrome of inappropriate antidiuretic hormone secretion 156
Syndromic epilepsies 446
Systemic antifungal
agents 59
therapy 56
Systemic autoimmune disorders 146
Systemic disorders 45
Systemic fungal infections 57
diagnosis of 57, 58t
Systemic inflammatory response syndrome 10
Systemic lupus erythematosus 47, 141, 146, 296, 300, 302, 325, 327
Systemic mycoses 57f
Systemic sclerosis 325
Systemic vascular resistance 4, 9, 13
T
Tachycardia 4, 29, 144, 172f
Taliglucerase alpha 351
Target sign 466
Teratoma 309, 312
benign 312
Testis 318
Testosterone 438
Tetracycline 290
Tezacaftor 209
Theophylline 314
Therapeutic drug monitoring 70
Therapeutic plasma exchange 153
Thrombotic thrombocytopenia, vaccine induced 109
Thyrocalcitonin 318
Thyroid
adenoma 318
peroxidase antibodies 147
Thyroiditis 290
Tinnitus 417
Tissue
hypoxia, measurement of 8
perfusion, inadequate 2
transglutaminase antibodies 147
Tocilizumab 154, 325, 330
Tofacitinib 336
Topiramate 456
Toxic encephalopathies 146
Toxic shock syndrome 46
Toxicity 75, 76
Tranexamic acid 206
Transaminitis 331
Transcription activator-like effector nuclease 353
Transcription inhibitors, activation of 335
Transepidermal water loss 499
Transepithelial sodium chloride absorption 253f
Trans-fatty acids 20
Trauma 446
Tremors 29
Triazoles 62
Triglycerides 25
Triiodothyronine 317
Triplet repeat disorders 344
Troponin 48
Tubercular meningitis 86
Tuberculin skin test 328, 329
Tuberculosis 325, 328, 329
Tuberous sclerosis complex 162
Tubular disorders 243, 261
Tubular dysfunction, patterns of 244
Tubular reabsorption 243
Tubulopathy 252
Tumbler test 86
Tumor 318
markers 307, 308, 317
necrosis factor 317, 324, 329, 438
screening 150
tissue 307
Turner syndrome 231, 284
Tyrosinemia 252, 309
U
Umbilical cord, care of 504
Upper airway resistance syndrome 363
Urinary catecholamines 313
Urine organic acids 164
Ursodeoxycholic acid 208, 237
Urticaria 29, 223
Ustekinumab 335
V
Vaccine
efficacy 117
inactivated 103
platforms 103
Vagal nerve stimulation 456
Valsalva maneuver 176
Valvular pulmonic stenosis, severe 173f
Vanillylmandelic acid 313
Varicella 290
Vascular endothelial growth factor 317, 357
Vasculitis 93, 325, 333
Vasoactive intestinal
peptide 318
polypeptide 316
Vasopressin 13
Velaglucerase alpha 351
Vena cava
inferior 8
superior 14
Verapamil 178
Vernix caseosa 501
Vesicular stomatitis virus 103
Vestronidase 351
Viable epidermis 499
Vigabatrin 166
Violence, forms of 479b
Vipoma 318
Viral infection 146, 204
Viral myocarditis 47, 173f
Viral prodrome 141
Viral transmission 42
Viral vectored vaccines 103
Vitamin
D 223
deficiency 193
dependent rickets 258
excess 260
deficiency 193
Vitiligo 278
Volume resuscitation 11
Vomiting 45, 464
Voriconazole 59, 6264, 67, 71
W
Warm autoimmune hemolytic anemia 292, 293f, 299b
treatment of 296
West syndrome 161
Wheezing, recurrent 193
White blood cell 93
Whole exome sequencing 164, 348
Whole genome sequencing 348
Wilms tumor 309, 310, 316, 318
Wilson disease 252
Wolff-Parkinson-White syndrome 174, 174f, 178
Wound management 434
X
X-linked dominant 344
X-linked hypophosphatemic rickets 344
Y
Y-aminobutyric acid-B receptor 141
Yolk sac tumor 309, 310
Z
Zero fluoroscopy procedures 180
Zinc-finger nuclease 353
Zollinger-Ellison syndrome 318
Z-score 193
×
Chapter Notes

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Neonatology

Neonatal ShockCHAPTER 1

Shiv Sajan Saini,
Abhishek Somasekhara Aradhya
 
INTRODUCTION
Shock is a clinical syndrome of acute circulatory dysfunction, resulting in insufficient delivery of oxygen, and vital nutrients to the body tissues relative to their metabolic demand. The resultant ischemic conditions lead to anaerobic metabolism, increased production of lactic, and inorganic acids. Progressively worsening cellular hypoxemic and acidotic conditions lead to deterioration in the functioning of various organ system(s) including cardiorespiratory, neurological, metabolic, hematological, renal, and endocrine functions. Continued worsening culminates in multiorgan failure and eventually death. The case fatality rates in neonatal shock are very high. Therefore, early recognition and appropriate intervention are the key for improved survival and better neurodevelopmental outcomes.1,2
 
INCIDENCE
There is extremely limited data published on the incidence and spectrum of neonatal shock. The incidence of shock in neonatal intensive care units (NICUs) is variable and depends on the population characteristics and study setting. The incidence of hypotension is inversely proportional to the gestational age. Almost 50% of very low birth weight (VLBW) neonates experience at least one episode of hypotension in NICU. The incidence of shock varies between 3 and 10% of NICU admissions. The incidence increases to 10–28% in extremely preterm neonates and is around 4% in those born at <36 weeks gestation.3 A study published from the British Columbia Children's Hospital (Vancouver, Canada) found 15% incidence (249 episodes in 1,641 admissions) of neonatal shock among full-term neonates.4 A recent study from a tertiary care referral hospital from north India reported 12.0% incidence (95% confidence interval: 10.9–13.2%) of shock among 3,271 admissions over 2-year time period.5 While the cardiogenic shock is likely to be more common the developed countries among term neonates, septic shock is the most common form of shock in term and preterm neonates on developing countries setting.4,5
 
PATHOPHYSIOLOGY
Inadequate tissue perfusion in a state of shock leads to reduced oxygen and nutrients delivery, increased oxygen consumption, and inadequate oxygen utilization.6 In the initial stages of shock, there is redistribution of blood in various organ systems of the body. The circulation to vital organs, i.e., brain, heart, and adrenals is maintained at the cost of nonvital organs such as skin, muscles, gut, lungs, etc.2 This phenomenon is known as “diving reflex”. In the early stages of shock, the compromised tissue perfusion clinically manifests as a change in the color of the skin (pale or off-colored skin), decreased skin temperature (cold peripheries), reduced pulse volume (thready pulses), delayed capillary refill time (CRT), and decreased urine output. The blood pressure (BP) is usually maintained at this stage. This physiological state is commonly referred to as peripheral circulatory failure or compensated shock. Later with the involvement of vital organs, myocardial performance decreases, and adrenal dysfunction sets in. The BP drops (hypotension) at this stage, which is referred to as decompensated shock. Although the terms “shock” and “hypotension” are loosely used interchangeably, it is important to realize that hypotension is a late manifestation of shock.7 As the neonate transitions from compensated to decompensated shock, the outcome worsens, and risk of mortality increases.
Shock happens due to derangement in one or more of three important contributors of circulation, i.e., preload, myocardial conductivity, and afterload. Decreased preload leads to improper filling of heart, thereby reducing the myocardial output. Preload is decreased in hypovolemic shock and tension pneumothorax. Contrastingly preload can be increased in some etiologies of shock involving poor myocardial contractility such as asphyxia and transitional circulation. Generally myocardial contractility is decreased in shock such as asphyxia, arrhythmias, and transitional circulation. However, myocardial contractility is increased in hyperdynamic circulation such as hemodynamically significant patent ductus arteriosus (hs-PDA) and in early stages of septic shock. In late stages of shock, myocardial contractility is universally decreased. Changes in afterload depends upon the state of shock. Afterload is increased to variable extent in early stages (except distributive shock namely septic and anaphylactic) owing to increased sympathetic activity as body's compensatory response. However, afterload is decreased with the onset of the decompensated shock. Table 1.1 presents the summary of pathophysiology of different etiologies of shock in neonates.
 
ETIOLOGY
Various etiologies can cause shock in neonates.8-10 These include (but are not limited to) perinatal asphyxia, circulatory maladaptation during transition from fetal to neonatal life (especially in extreme preterm neonates), intracardiac shunts, sepsis, fluid loss, adrenal insufficiency, arrhythmias, and raised intrathoracic pressure.3
Table 1.1   Pathophysiology of neonatal shock in different etiologies.
Clinical scenario
Preload
Myocardial contractility
Afterload
Main mechanism
Hypovolemia, e.g., fetomaternal bleed, intracranial bleed, etc.
Decreased as intravascular volume is reduced
Not affected
Not affected and may slightly increase initially
Predominantly decreased preload
Septic shock
Relative hypovolemia due to venodilation
Initially hyperdynamic but later depressed myocardial functions
Decreased vasomotor tone
Mainly vasomotor dysregulation but all sectors affected
Asphyxia
Increases
Depressed due to myocardial injury
Increases initially, at later stages decreases
Predominantly myocardial dysfunction
Intracardiac shunts
e.g., PDA
Increases
Increased myocardial work due to hyperdynamic circulation, not able to meet demands of body
Decreased due to systemic to pulmonary shunts
Predominantly myocardial dysfunction and decreased afterload
Transitional circulation in ELBW neonates
Increases
Depressed (suddenly increased LV afterload after birth)
Increases in early stages; decreases later
Predominantly myocardial dysfunction
Adrenal insufficiency
Variable
Depressed
Decreased
Combination of decreased afterload and myocardial dysfunction
Raised intrathoracic pressure, e.g., pneumothorax and high pressures on ventilator, etc.
Decreased (poor venous return)
Not affected primarily, however, low output due to poor myocardial capacity to distend
Increases as intrathoracic pressure compresses vessels
Mainly-decreased preload and poor cardiac filling
(ELBW: extremely low birth weight; LV: left ventricle; PDA: patent ductus arteriosus)
4
There is extremely limited data regarding the etiological spectrum of shock in neonates. Only one study from a tertiary care referral NICU of a developed country has defined the spectrum of etiologies of neonatal shock.4 These authors found cardiogenic shock as a most typical cause of shock among term neonates. On the contrary, septic shock is the main type of shock in the developing countries especially in preterm neonates. A prospective observational study done in a tertiary care set up showed that three most common reasons of shock in neonates include septic shock, severe birth asphyxia, and hemodynamically significant PDA.11
 
CLINICAL FEATURES
Shock at the bedside is commonly assessed by macrohemodynamic parameters which include heart rate, pulse volume, temperature (core and peripheral), BP, CRT, color, and urine output. As hypotension is a late sign of shock, signs of the peripheral circulatory failure (i.e., compensated stage) should be recognized at an earlier stage to achieve better outcomes. The clinical manifestations of shock are detailed below.
 
Heart Rate Abnormalities
Tachycardia (heart rate > 160/min) is a nonspecific finding commonly seen in shock. Tachycardia indicates compensatory mechanisms of the neonate to increase cardiac output as neonatal heart has a limited ability to increase stroke volume.11 Bradycardia is a preterminal finding. There are numerous other common causes of tachycardia in newborn especially dehydration, pain, PDA, drug effect (caffeine), sepsis, etc. Therefore, tachycardia is nonspecific and should be combined with other clinical features for the diagnosis of shock.
 
Hypotension
Hypotension refers to BP below fifth centile for the gestational and postnatal age. Table 1.2 depicts BP thresholds at fifth centile as per gestational age (modified from McNamara et al.).12 Traditionally, BP is used to measure adequacy of the systemic circulation. However, BP has following caveats for assessment of hemodynamic stability in neonates:
  • It is well known that low BP is a late marker of shock.
  • Blood pressure is a product of cardiac output and systemic vascular resistance (SVR). Decreased cardiac output may be masked if SVR is elevated. However, tissue perfusion decreases if cardiac output is decreased. Thus, despite BP being stable during shock, the tissue perfusion may be seriously compromised.5
    Table 1.2   Blood pressure (BP) thresholds at fifth centile as per gestational age.
    Gestation (weeks)
    Fifth centile (mm Hg)
    Systolic
    MAP
    Diastolic
    <30
    42
    30
    20
    31
    45
    30
    20
    32
    46
    30
    21
    33
    47
    30
    22
    34
    48
    31
    23
    35
    49
    32
    24
    36
    50
    32
    25
    (MAP: mean arterial pressure)
  • Blood pressure obtained by noninvasive methods such as oscillometry and invasive methods have a wide range of confidence limits of agreement. In hypotensive neonates, BP obtained by noninvasive methods is higher than invasive methods. On the contrary, noninvasive BP is lower than invasive BP in hypertensive neonates. Thus, there is a poor agreement between noninvasive and invasive BPs under pathological conditions.1-9-10-13 BP by noninvasive methods measure mean arterial pressure (MAP) and estimate systolic and diastolic BP by mathematical algorithms. Hence, MAP should be given more importance than systolic or diastolic BP, when measured by noninvasive methods.
  • Furthermore, “normal” range of BP is not clear for various gestational ages and postnatal ages. The available charts give statistical cutoffs of data obtained from limited number of neonates at a particular gestation age and postnatal age. The statistical cut-off does not necessarily translate into abnormal circulation.
  • Another challenge with BP is that it correlates poorly with systemic blood flow especially in extreme prematurity. Sometimes in borderline low BP situations, subjects can have adequate perfusion as they have adequate cardiac output. In these situations, signs of peripheral circulations are normal and metabolic status is maintained. Thus, BP needs to be interpreted cautiously in neonates by assessing the range of clinical signs of perfusion.14
Apart from hemodynamic assessment, BP measurement helps to identify ductal dependent systemic circulation, where BP in lower limbs may be lower than right upper limb.
 
Delayed Capillary Refill Time
Capillary refill time is assessed over bony surface like sternum or forehead. Delayed CRT beyond 4 seconds in presence of hypotension and/or 6tachycardia or other signs indicate shock. Contrasting “flash” refill (along with bounding pulses and low BP) is seen in conditions of decreased SVR and indicates shock (warm shock).
 
Other Signs of Hemodynamic Monitoring
Low pulse volume or thready pulses, core-peripheral temperature difference of >3°C (mainly for term neonates), and pale color indicate inadequate perfusion.
 
Signs of Other Organs Involvement due to Poor Perfusion
 
Neurologic Signs
Nonspecific signs such as lethargy, irritability, poor tone, and poor neonatal reflexes can be present. Decreased cerebral perfusion can also cause periodic breathing or apnea.
 
Respiratory Signs
Tachypnea is a common finding either due to lung involvement by sepsis or as a compensatory response to metabolic acidosis.
 
Renal Signs
There is a good correlation between reduced urine output and hypotension. However, there is a significant time lag between oliguria and hypotension.
Though there are many clinical signs of hemodynamic assessment, these signs have some limitations. While some of the signs of peripheral circulation are nonspecific, e.g., heart rate; some others are subjective, e.g., feeble pulses. Individually CRT and core-periphery temperature difference correlate poorly with organ perfusion.13,15 BP measurements also have many caveats. It is clear from the above discussion that no single parameter in isolation can accurately detect shock especially in early stages. Therefore, combined information of all parameters [heart rate, CRT, color, urine output, temperature (core and peripheral temperature), and BP] should be utilized for assessment of circulation.16
Due to the subjective nature of many of the signs of hemodynamic assessment, a requirement of objective definition of shock was felt. An objective definition of septic shock was proposed by International Pediatric Sepsis Consensus Conference.17 Septic shock is defined as presence of cardiovascular dysfunction in presence of sepsis. Cardiovascular dysfunction is defined, if neonate has either of following criteria despite administration of isotonic intravenous (IV) fluid ≥ 40 mL/kg in 1 hour:
  • Decrease in BP (hypotension) < fifth percentile for age or systolic BP <2 SD (Standard deviation) below normal for age, OR
  • Need for vasoactive drug to maintain BP in normal range (dopamine > 5 μg/kg/min or dobutamine, epinephrine, or norepinephrine at any dose), OR7
  • Two of the following: Unexplained metabolic acidosis: base deficit > 5.0 mEq/L; increased arterial lactate > 2 times upper limit of normal; oliguria: urine output <0.5 mL/kg/hr; prolonged capillary refill: >5 sec; and core to peripheral temperature gap > 3°C.
However, this definition is applicable only for term neonates. Wynn and Wong proposed a modified definition for preterm neonates.10 The salient differences in definition for preterm neonates (from International Pediatric Sepsis Consensus Definition) are: fluid administration limit is >10 mL/kg in infants < 32 weeks, systolic BP < 2 SD, or MAP < 30 mm Hg with CRT > 4 seconds. Although this definition is given for the diagnosis of neonatal septic shock, it may be used for the diagnosis of other types of shock.
 
INVESTIGATIONS
Shock is a clinical diagnosis. Laboratory investigations aid in categorizing severity and etiology of shock. The laboratory evaluation includes metabolic, biochemical, hematological, and microbiological workup.
The correctable metabolic/biochemical derangements should be screened and managed upfront in all cases, which include blood glucose levels, serum electrolytes, and serum calcium. Hypoglycemia and electrolyte disturbances (especially hypocalcemia and hyperkalemia) should be treated aggressively.
Blood gas analysis is a useful means to get information about metabolic status as well as respiratory gas exchange. Modern blood gas machines are also capable of measuring serum electrolytes including ionized calcium levels, hematocrit, blood glucose as well as serum lactate levels. Elevated lactate (>4 mmol/L) and mixed venous saturation are not good markers of shock in neonates.1,10 Apart from systemic hypoperfusion states, lactate is also produced in local ischemic conditions and even in neonatal sepsis without shock. Furthermore, its levels may increase in the presence of liver dysfunction as it causes decreased metabolism of lactate. After initiation of management of shock, lactate levels can transiently rise with improvement in circulatory status as the lactate from under-perfused tissue beds shifts to central circulation. Nevertheless, standalone lactate levels can be used along with other hemodynamic variables and blood gas values to define shock. Moreover, serial lactate values will be helpful in monitoring the response to therapy.
Hematological workup includes assessment of hematocrit, complete blood count (CBC), and platelet levels. In sepsis, leukocyte counts may be either elevated or low (predominantly leukopenia in neonates). In addition, absolute neutrophil count can be low and immature to total neutrophil ratio (ITR) can be elevated (>0.2).
Microbiological investigations must be performed whenever septic shock is considered. Blood culture should be obtained before giving the first dose of antibiotics. Culture of cerebrospinal fluid (CSF) should be sent in all cases of 8sepsis once the neonate is stabilized. Site-specific infective focus (aspirates, swabs, etc.) should be cultured, wherever indicated. If viral infections (especially Herpes simplex virus or enteroviruses) are suspected, appropriate serological, or polymerase chain reaction (PCR) tests should be performed to identify causative organisms.18
 
Functional Echocardiography
Functional echocardiography has gained importance for hemodynamic assessment in the last few years.19
For preload assessment, inferior vena cava (IVC) collapsibility is proposed. There is currently not enough literature in neonates to support its use in preload assessment. Nevertheless, presence of collapsing IVC during inspiration, and narrower left ventricular cavity (opposite papillary muscles encountering each other during systole, i.e., kissing sign) suggests depleted intravascular volume status. These echocardiographic markers should be used along with body weight, urine output, serum sodium, and osmolality to assess preload status.
Assessment of cardiac systolic functions is done with the help of ejection fraction, fractional shortening, rate-corrected velocity of myocardial fiber shortening, etc.
Assessment of diastolic functions is done with the help of early to atrial peak systolic velocity ratio, isovolumetric relaxation time, etc.
There is no parameter to directly measure SVR. SVR is indirectly estimated by the following formula:
Cardiac output (CO): BP = CO × SVR
Functional echocardiography can be a useful supplement to the clinical examination especially in preterm neonates. Additionally, functional echocardiography can help to exclude common mimickers of sepsis like hemodynamically significant PDA, duct dependent systemic circulation such as hypoplastic left heart, coarctation of aorta, etc. Details of functional echocardiography are beyond the scope of the current text which is available in published reviews on this topic.19
 
Measurement of Tissue Hypoxia
Central venous pressure, mixed venous oxygen saturation (SvO2), and arteriovenous difference have been used to assess tissue hypoxia. Although useful, their widespread use is limited due to the invasive nature of the measurement and technical challenges in neonates. There is limited experience for assessing microcirculatory parameters (e.g., near infrared spectroscopy [NIRS], plethysmographic signal of pulse oximeter-perfusion index, and visible light technology) in the management of neonatal shock.20
The hemodynamic parameters get affected variably in the different form of neonatal shock. Table 1.3 shows the alteration in hemodynamic parameters among four main categories of neonatal shock.9
Table 1.3   Hemodynamic parameters in main categories of neonatal shock.
Shock type
Preload
Myocardial
Afterload
Central venous pressure
Left atrial pressure
Contractility
Cardiac output
Systemic vascular resistance
Blood pressure (BP)
Hypovolemic
↓↓↓
↓↓↓
↔ or ↑
↔ or ↓
Cardiogenic
Systolic
↑↑
↑↑
↓↓↓
↓↓
↑↑
↔ or ↓
Diastolic
↑↑
↔ or ↓
↑↑
↔ or ↓
Obstructive
↑↑
↑↑
↔ or ↓
Septic
Early
↔ or ↑
↑↑↑
↓↓↓
↔ or ↓
Late
↔ or ↑
↓↓
↓↓
↓↓
Note: Adapted from Nelson Textbook of Pediatrics, 21st edition.
 
APPROACH TO MANAGEMENT
The management of shock can be divided into stabilization of the neonate and definitive therapy. It is important to know the cause of shock to plan the definitive therapy. The management begins with the stabilization of the neonate which is dealt in the next section. The following Table 1.4 depicts the history, clinical clues, and investigative parameters to find the etiology of shock.
 
TREATMENT
Initial stabilization involves maintenance of TABC (temperature, airway, breathing, and circulation).
  • As with all emergencies in neonates, the management of shock starts with provision of a thermoneutral environment.
  • The airway is stabilized followed by breathing support either with CPAP or mechanical ventilation depending on the severity of respiratory distress and hemodynamic compromise. Although CPAP can be tried in early stages of shock (e.g., compensated shock), it may be preferable to intubate and start elective positive pressure ventilation in presence of hypotension or requirement of more than one vasoactive agent.
  • An IV line is required for fluid/vasoactive drugs administration. With initiation of vasoactive agents, enteral feeds should be stopped, and IV fluids should be started. Central venous access [umbilical venous on first day of life or peripherally inserted central catheter (PICC) line] is preferable for reliable delivery of vasoactive drugs. Vasopressors should preferably be given through central line.
The management of neonatal shock is presented in Flowchart 1.1.10
Table 1.4   Etiologies of various forms of neonatal shock.
Types of shock
Etiologies of shock
History
Clinical clues
Investigative parameters*
Hypovolemic
Loss of body fluids (blood and water/electrolyte)
Concealed or revealed hemorrhage, diarrhea, and polyuria
Clinical signs of dehydration may be present
  • Serum sodium and osmolality may be raised
  • Functional echocardiography can help in doubtful situations
Cardiogenic
  • Birth asphyxia, congenital heart diseases cardiomyopathies, arrhythmias
  • Electrolyte abnormalities: Hypocalcemia, severe anemia, and drugs, e.g., opioids and magnesium sulfate
  • Birth asphyxia
  • Antenatal-diagnosed congenital heart diseases
  • Interrupted feeding/perspiration during feeding, history of maternal/neonatal drug use
  • Maternal diabetes and antenatal scans
  • Signs of congestive cardiac failure
  • Murmurs
  • Hydrops
  • Severe pallor
  • Biomarkers (CK-MB)
  • Serum electrolytes
  • ECG abnormalities
  • Echocardiography
Obstructive
  • Increased intrathoracic pressure: Tension pneumothorax, increased intrathoracic ventilator pressure
  • Ventricular outflow obstruction: Ductal dependent CHDs and pulmonary embolism
  • Pericardial tamponade
  • Resuscitation details
  • Positive pressure ventilation
  • Antenatal scans
  • Known congenital heart diseases
  • Asymmetric chest rise/auscultatory findings
  • Feeble femoral pulses
  • Presence of central lines
  • Chest X-ray
  • Blood gas analysis
  • Upper and lower limb BP
  • Echocardiography
Distributive/septic
  • Early septic shock with decreased afterload (bacterial, viral, or fungal)
  • Anaphylaxis
  • Loss of sympathetic vascular tone secondary to spinal cord or brainstem injury
  • Drugs, e.g., β2 agonists
  • Maternal or postnatal risk factors of infection
  • Drug administration
  • Signs of SIRS
  • Multiple organ involvement
  • Sepsis markers
  • Culture of sterile body fluids (especially blood and CSF)
  • Organ specific investigations
(CHD: congenital heart disease; CK-MB: creatine kinase-muscle brain; CSF: cerebrospinal fluid; ECG: electrocardiography; SIRS: systemic inflammatory response syndrome)
Note: *This list is representative and not comprehensive.
11
zoom view
Flowchart 1.1: Algorithm for stepwise and time sensitive management of shock.Source: Modified from Davis et al.32(BP: Blood pressure; CHD: congenital heart disease; CRT: capillary refill time; ECMO: extracorporeal membrane oxygenation; IV: intravenous; MAP: mean arterial pressure; NRP: Neonatal resuscitation program; PCV: packed cell volume; PGE: prostaglandin E1; PT: preterm; SD: standard deviation)
 
Volume Resuscitation
Volume resuscitation is the first line of therapy in neonatal shock. Crystalloids (normal saline) are preferred over 5% albumin as they are associated with lower risk of fluid overload. Further albumin is associated with increased risk of infection and impaired gas exchange.15 Initial fluid bolus of 10 mL/kg (irrespective of gestational age) is infused over 15–30 minutes [longer duration for extremely low birth weight (ELBW) neonates]. Up to 40–60 mL/kg 12is advised for term neonates and 20–30 mL/kg for preterm neonates.1,10,16 The conservative fluid resuscitation in preterm neonates is advised due to increased risk of fluid overload, opening of PDA, and intraventricular hemorrhage. Currently, there is no gold standard measure for preload optimization. Therefore, fluid resuscitation is guided by response to fluid bolus(s) and signs of fluid overload.18,19 Functional echocardiography may offer additional clues as discussed previously. It is important to realize that absolute hypovolemia is unlikely, except in conditions of blood loss or gastrointestinal (GI) losses. Thus, fluid should be used cautiously in the management of cardiogenic shock secondary to asphyxia, PDA, and transitional circulation where myocardial contractility is impaired.
 
Pharmacologic Therapy
The mainstay of pharmacologic therapy are three classes of drugs—inotropes, vasopressors, and lusitropes.8 Inotropes primarily increase myocardial contractility and hence are suitable for conditions in which myocardial dysfunction is primary problem, e.g., birth asphyxia or transitional circulation, etc. Vasopressors improve BP through increase in vascular tone and are thus suitable for conditions with decreased afterload, e.g., septic shock and/or in presence of hypotension. Lusitropes improve myocardial relaxation, increase systemic blood flow, and are thus useful for conditions with diastolic dysfunction. Appropriate vasoactive agents should be chosen based on the underlying pathophysiology and intended effect. A single drug can have either inotropic or vasopressor effect depending on its infusion rate. Commonly used agents in neonates, their doses, and their predominant actions are summarized in Table 1.5.1,8,10,15,21
Generally, inotropes are advised in peripheral circulatory failure with normal BP. Vasopressors are used in hypotension. Depending on the underlying pathophysiological mechanism, the initial choice of vasoactive agents may vary. The choice of vasoactive agents in different clinical scenarios is discussed below.
 
Shock in Transitional Circulation
Although usually practiced, fluid resuscitation should be cautiously used as generally there is no setting of volume loss. Inotropes (dopamine 5–10 μg/kg/min or dobutamine 5–20 μg/kg/min) should be started initially to support poor myocardial performance. If there is hypotension, vasopressors are required. However, vasopressors should be carefully used as they can markedly increase SVR, thereby decreasing cardiac output further. A stepwise titration of low to moderate dose dopamine and epinephrine is advised in hypotensive neonates to achieve mean BP 3–6 mm Hg higher than that for the gestational age.22,2313
Table 1.5   Vasoactive drugs, dose, and important actions.
Agent
Dose
Action
Special features
Dopamine
5–9 µg/kg/min, mainly on β-receptors
↑ HR and ↑ myocardial contractility
  • 5% dextrose is preferred for dilution. Preferable to change infusions every 12 hours rather than 24 hours22
  • Acts by releasing stored norepinephrine; the stores might exhaust with continuing shock
  • Thyroid screening to be postponed till 12 hours after the drug is stopped
10–20 µg/kg/min (vasopressor), additionally on α-receptors
↑ BP by increasing systemic vascular resistance (SVR)
Dobutamine
5–20 µg/kg/min
↑ contractility, cardiac output, and ↓ SVR
Direct actions on β-receptors. Effective in presence of myocardial dysfunction
Epinephrine
0.1–0.2 µg/kg/min (inotropy)
↑ contractility and HR
  • Direct actions on adrenergic receptors
  • Caution beyond 0.5 μg/kg/min as arrhythmias may happen
  • Adverse effect includes ↑ HR, serum lactate, and hyperglycemia
≥0.3–1 µg/kg/min (vasopressor)
↑ SVR
Milrinone
Loading: 50–75 μg/kg IV over 60 min; Maintenance: 0.25–0.75 μg/kg/min
Both inotropy and lusitropy
↓ Vascular tone in pulmonary and systemic circulation
  • Main role in postcardiac surgery
  • Useful adjunct to iNO in presence of PPHN
  • More effective than dobutamine in presence of diastolic dysfunction
  • Cautious in presence of hypotension
Vasopressin
0.01–0.12 units/kg/hr
↑ SVR; releases cortisol in presence of ACTH
  • Indicated in warm and vasopressor resistant shock
  • Caution in presence of myocardial dysfunction
  • Watch for oliguria as ↓ renal blood flow is known
Noradrenaline
0.02–1 µg/kg/min
↑ SVR
Limited evidence of efficacy
Levosimendan
0.1–0.4 µg/kg/min
Positive inotropy and lusitropy
↓ SVR
  • Limited evidence of efficacy
  • Useful in postoperative care of congenital heart diseases
(ACTH: adrenocorticotropic hormone; HR: heart rate; iNO: inhaled nitric oxide, PPHN: persistent pulmonary hypertension of the neonate; SVR: systemic vascular resistance)
14  
Very Low Birth Weight Neonates with Hemodynamically Significant Patent Ductus Arteriosus
The principles of management include restoring hemodynamic stability as well as pharmacological closure of PDA. To decrease left-to-right shunt through PDA, one should use maneuvers to keep slightly higher pulmonary vascular resistance, e.g., adjusting ventilator settings to avoid hyperoxia, keeping PCO2 values on the higher side of normal range, higher positive end expiratory pressure, etc. There are no well-controlled trials comparing different vasoactive agents in the management of shock in neonates with PDA. Bouissou et al. found that dopamine (<10 μg/kg/min) increased BP and systemic blood flow in preterm hypotensive neonates with PDA.24 Therefore dopamine in inotropic doses (5–10 μg/kg/min) or dobutamine (10–20 μg/kg/min) should be the first line of management in such cases. Epinephrine (0.1–0.5 μg/kg/min) should be used if there is no response to dopamine and dobutamine.25
 
Shock in Neonates with Severe Birth Asphyxia
In severely asphyxiated neonates, multiple derangements such as capillary leak syndrome, myocardial dysfunction, and persistent pulmonary hypertension of the neonate (PPHN) may occur together. Therefore, therapy must be individualized and constantly adjusted.9 Fluids should be given cautiously in absence of setting of volume loss. In normotensive patients with poor peripheral circulation, dobutamine should be used. In normotensive neonates with presence of poor peripheral circulation and concomitant PPHN, milrinone can be considered. In cases of hypotension, dopamine ≥10 μg/kg/min should be started and gradually titrated. Inhaled nitric oxide should be considered for neonates with PPHN, poor cardiac indices (<3.3 L/m2/min) or poor superior vena cava (SVC) flow (<40 mL/kg/min).1,10
 
Septic Shock
Fluid resuscitation should be given initially as there is relative hypovolemia. The initial choice of vasoactive drug is dopamine (10–20 μg/kg/min) in hypotensive neonates. Epinephrine (0.2–0.5 μg/kg/min) should be added, if neonates remain hypotensive despite dopamine infusion. Use of epinephrine as a first line vasoactive drug is upcoming, however, currently there is no conclusive evidence of its superiority over dopamine.26 In contrast, a normotensive septic neonate, with signs of peripheral circulatory failure, should be treated with dobutamine or dopamine (5–10 μg/kg/min).1,10
 
Late-onset Glucocorticoid Responsive Circulatory Collapse
It occurs after the first week of life in VLBW infants in the absence of other common causes such as sepsis, PDA, blood loss, or other obstructive causes 15of shock. Relative adrenal insufficiency is implicated in its pathophysiology. It is characterized by sudden-onset hypotension which is usually resistant to fluid resuscitation and vasoactive support. Hydrocortisone is given at 1.0 mg/kg every 6–8 hourly till 48 hours followed by 1 mg/kg 12 hourly for next three days. If poor response persists vasopressin can be considered.27,28
 
Catecholamine-resistant Hypotension
Steroids are indicated at the onset of catecholamine-resistant hypotension. There is no universal definition of catecholamine resistant hypotension but most followed definition is persistence of shock despite >10 µg/kg/min dopamine and a directly acting vasoactive agent (either epinephrine > 0.3 µg/kg/min or dobutamine > 10 µg/kg/min). They increase BP and decrease vasopressor requirement in such neonates.29 Given the lack of long-term safety data of steroids on developing brain and prolonged half-life of steroids in preterm neonates, lower doses are preferred. Hydrocortisone is given at 1.0 mg/kg every 6–8 hourly till 48 hours followed by 1 mg/kg 12 hourly for next three days.30
 
Supportive Management
Broad-spectrum antibiotics (as per the local sensitivity pattern) should be started, wherever the possibility of sepsis cannot be ruled out. First dose should be administered as early as possible within the first hour of shock. Enteral feeds should be withheld. However, trophic feeding can be continued, if abdominal examination is normal and shock is in improving trend. Parenteral nutrition may be considered. Routine sedation is not required. Avoid hyperglycemia and maintain electrolytes and calcium in their normal range. Maintain hematocrit > 35%. In bleeding tendencies, vitamin K injection, platelet concentrates for platelet count <50,000/mm3, and fresh frozen plasma (FFP) transfusions should be considered for coagulopathy. Consider urgent chest tube drainage if there is pneumothorax. Consider venoarterial extracorporeal membrane oxygenation (ECMO) for refractory shock.1
Other specific management like prostaglandin E1 (PGE1) can be considered to maintain systemic circulation, if duct-dependent systemic circulation is suspected.
 
OUTCOMES
Neonates with shock are likely to have longer duration of hospital stay, chronic lung disease, growth failure, retinopathy of prematurity, and adverse neurodevelopmental outcomes. Mortality rates up to 40–50% are reported in VLBW in various studies from developed nations; and studies from developing countries have shown 70–80% mortality in septic shock. A recent hospital-based study from India reported the case fatality rates of 62% in neonatal shock among 392 neonates developing shock over 2-year study period.5 16Poor prognostic factors in such studies are refractory shock at onset, acute renal failure, disseminated intravascular coagulation (DIC), neutropenia, metabolic acidosis, and hypothermia.10 Neurodevelopmental outcomes following septic shock at 18 months of age show higher risk of impairment especially in preterm neonates. Severe sequelae either cerebral palsy, visual impairment, severe developmental delay, or short bowel syndrome have been described up to 19% at 18 months follow-up and the combined risk of death or severe sequelae in half of them.31,32
 
CONCLUSION
Hypotension is a late marker of shock. Septic shock is the most common form of shock in neonatal age group especially in the developing countries. Early recognition of shock at the compensated stage and appropriate intervention can maximize survival and neurodevelopmental outcomes. Apart from the clinical signs, laboratory parameters such as base excess and lactate may be useful in identification in borderline cases. Functional echocardiography is a noninvasive tool for assessment of neonates with shock. The management of shock begins with IV fluid resuscitation unless there is clear evidence that the preload is optimum in the neonate. Conventionally, dopamine is the first-line inotrope for fluid-refractory neonatal shock. However, the choice of vasoactive agent(s) may change with the underlying pathophysiology. Hydrocortisone should be given in catecholamine resistant shock. Despite everything, the case fatality rates are astonishingly high.
 
KEY POINTS
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