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Basic Paediatric Management Edited by Daniel K. Ng, MD, M Med Sc Yuen Yu Lam, FHKAM(Paed) Lettie C. Leung, FHKAM(Paed) Sharon W. Cherk, FHKAM(Paed) Eric Y. Chan, FHKAM(Paed) Fourth Edition Published in 2014 Printed in Hong Kong SAR, China Disclaimer: Considerable care has been taken to see that the information is accurate. Nevertheless the user is advised to exercise clinical judgment. The authors shall not be responsible for any errors. Opinions expressed by the contributors do not necessarily reflect that of the Department of Paediatrics, Kwong Wah Hospital. I Preface to Fourth Edition 2014 is a special year for the Department of Paediatrics, Kwong Wah Hospital as it was founded 85 years ago in the delivery rooms of this hospital. We are privileged to work with the excellent staff of this department. To make their works simpler, we publish this White book nearly 10 years ago in 2005. We receive a lot of suggestions for improvement since the third edition in 2010. The main focus for this issue is to simplify without losing the essential information that allows the front line doctors practical application of the information to save the sick children. We hope this White book does make a difference for that doctor in treating that particular child as every child counts dearly in our hearts. Daniel K. Ng Yuen-yu Lam Lettie C. Leung Sharon W. Cherk Eric Y. Chan December 2014 DK Ng, [email protected] Department of Paediatrics Kwong Wah Hospital Waterloo Road Hong Kong SAR, China II Preface to Third Edition The major change in this edition sees the appointment of section editors to improve on each section. I express my deepest gratitude to my colleagues, Dr. YY Lam (Neonatology, Endocrinology), Dr. PY Chow (Respirology), Dr. KL Kwok (Cardiology), Dr. S Cherk (Neurology), Dr. WF Lau (Gastroenterology) and Dr. L Leung (Nephrology) who put in tremendous effort to make this small book useful for the newcomers to paediatrics. I hope this book will provide that extra little help in the daily works of paediatricians. DK Ng MT Soo April 2010 Department of Paediatrics Kwong Wah Hospital Waterloo Road Hong Kong SAR, China III Preface to Second Edition We are much encouraged by the enthusiastic response to the first edition of the manual. A lot of comments were received by the editors. The comments are now incorporated into the second edition together with a number of new chapters that we believe are important for the basic delivery of paediatric care in this department. Daniel K. Ng, [email protected] Ka-li Kwok Pok-yu Chow Man-ting Soo Department of Paediatrics Kwong Wah Hospital Waterloo Road Hong Kong SAR, China Summer 2007 IV Preface to First Edition In the last few years we have been seeing an increasing number of medical staff on short rotation for 3 months in this department. We perceive the need to equip them with essential information during the first week of duty in the department so as to allow them to manage common diseases. This book for the common diseases encountered in the paediatric wards or clinics is intended to meet this need. The book is set out in short note form to allow easy reading. To keep the size to a minimum, references are not included in the text. The preparation of this pocket guide has involved many people of this department. Each topic is prepared by at least one specialist staff based on the available literature and personal experience as well as biases. As such, the book should not be followed slavishly and clinical judgement should always be exercised. Comments are welcome from the readers and should be directed to the lead editor. We thank the contributors for giving their time, knowledge and experience to help us prepare this book. We acknowledge Annie Young for her great help in preparing the manuscripts of each chapter. Daniel K. Ng, [email protected] Ka-li Kwok Pok-yu Chow Department of Paediatrics Kwong Wah Hospital Waterloo Road Hong Kong SAR, China October 2005 V List of contributors: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 陳建平) 陳廣達) Dr Chan Mei-ching (陳美貞) Mr Chan Ping-shu Paul (陳平舒) Dr Chan Yat-tung Eric (陳日東) Dr Cherk Wan-wah Sharon (卓蘊樺) Dr Choi Mui-sum Kathy (蔡梅心) Dr Fung Tsui-hang Sharon (馮翠姮) Dr Ho Che-shun Jackson (何誌信) Ms Ho Mang-ying Emily (何孟瑩) Dr Kwok Ka-li (郭嘉莉) Dr Lam Yuen-yu (林琬瑜) Dr Lau Wing-fai (劉永暉) Dr Leung Chuk-kwan Lettie (梁竹筠) Ms Leung Nga Shan Phillis (梁雅珊) Dr Leung Ping Maurice (梁平) Dr Ng Kwok-keung Daniel (吳國強) Dr Pau Chee-kit Benjamin (包志傑) Mr Poon Man Hong Freddie (潘文康) Dr Soo Man-ting (蘇文庭) Dr Tse Wing-sze Cindy (謝詠詩) Dr Wong Chin-pang Jeff (黃展鵬) Dr Wong Lai Yin (黃麗燕) Ms Wong Siu-fong (黃少芳) Dr Yip Yuen Fong Ada (葉遠芳) Dr Yuen Chi-lap Angus (袁志立) Dr Yu Pui Tak (余佩德) Mr Chan Kin Ping ( Dr Chan Kwong-tat ( Pathology Resident Specialist Associate Consultant Deputy Department Manager (Pathology) Consultant Deputy Consultant Private Practice Associate Consultant Honorary Consultant Pharmacist Senior Medical Officer Consultant Associate Consultant Consultant Senior Medical Technologist Honorary Consultant Consultant Associate Consultant Pharmacist Associate Consultant Consultant Microbiologist Associate Consultant Consultant Ward Manager Associate Consultant Resident Specialist Resident Trainee VI Contents Preface List of contributors Section 1. Neonatology 1. Anaemia in neonates 2. Congenital syphilis 3. Feeding regime for VLBW (<1,500 gm) babies 4. Inborn errors of metabolism (A clinical approach) YY Lam MC Chan YY Lam MT Soo, J Wong, DK Ng, F Poon 5. Big baby (Macrosomia) YY Lam 6. Maternal thyroid disorders YY Lam, E Chan 7. Neonatal jaundice B Pau, YY Lam 8. Patent ductus arteriosus in preterm infant MC Chan, E Chan, KL Kwok, YY Lam 9. Persistent pulmonary hypertension of neonate (PPHN) MC Chan, E Chan, YY Lam 10. Management of neonates with risk factors of early onset MT Soo neonatal infection 11. Necrotizing enterocolitis (NEC) MT Soo, YY Lam, E Chan 12. Neonatal parenteral nutrition YY Lam, Freddie Poon 13. Transpyloric tube feeding in neonate E Chan, YY Lam 14. Surfactant therapy B Pau, YY Lam 15. Hypoxic-ischaemic encephalopathy B Pau, S Cherk 16. Brain death in the neonate S Cherk 17. Neonatal hypocalcaemia MC Chan, L Leung 18. Neonatal bacterial meningitis MT Soo, C Tse, YY Lam, F Poon 19. Paramortem studies for inborn error of metabolism MT Soo, L Leung, Phyllis Leung, KP Chan 20. Bronchopulmonary dysplasia (BPD) MT Soo, YY Lam 21. High frequency oscillation DK Ng 22. Neonatal narcotic withdrawal YY Lam 23. Normal Range of Neonatal Haematological Values MT Soo Section 2. Respiratory system 24. Allergic rhinitis DK Ng 25. Bacterial tonsillitis E Chan 26. Common cold (URI) E Chan, DK Ng 27. Childhood pneumonia E Chan 28. Chronic cough E Chan, DK Ng 29. Acute asthma E Chan, DK Ng 30. Ambulatory care of asthma E Chan, DK Ng 31. Acute bronchiolitis E Chan, DK Ng 32. Sleep-disordered breathing (SDB) DK Ng, E Chan 33. Parapneumonic effusion and empyema E Chan, DK Ng 34. Pulmonary function tests in children E Chan, J Wong, DK Ng VII II VI 10 11 13 17 20 28 29 31 39 42 45 48 50 53 54 56 62 64 66 69 72 76 77 81 83 84 85 86 87 89 91 95 99 102 106 109 35. Bronchoscopy 36. Preparation for endoscopy 37. Positive Mantoux test 38. Pulmonary tuberculosis 39. Primary spontaneous pneumothorax in adolescents 40. Modified bronchoalveolar lavage 41. Skin prick test 42. Primary ciliary dyskinesia and non-CF bronchiectasis 43. Nasal lavage 44. Reflux laryngitis 45. Normal values Section 3. Cardiovascular system 46. Ambulatory management of hypertension 47. Management of severe hypertension 48. Management of Kawasaki disease 49. Treadmill (Exercise stress test) 50. Treatment regime for patients with heart diseases that mandate prophylactic antibiotics 51. ECG criteria for LVH & RVH & prolonged QT interval Section 4. Central nervous system 52. Acute management of post-neonatal convulsion 53. Generalized convulsive status epilepticus (excluding neonates) 54. Febrile convulsion 55. Approach to a child with decreased conscious level (excluding neonates) 56. EEG 57. Sedation 58. Normal neuro-developmental milestones 59. Childhood epilepsy natural history (counselling) 60. Therapeutic hypothermia in paediatric patients (excluding neonates) 61. Tics and Tourette’s syndrome in childhood 62. Global developmental delay/ Intellectual Disability (Mental retardation) – diagnostic approach 63. Anti-convulsants use in children with epilepsy 64. Migraine 65. Neonatal seizure 66. Screening/quick reference : Cerebral Palsy 67. Screening/quick reference : Special note on management of various types of cerebral palsy Section 5. Gastrointestinal system 68. Acute gastroenteritis 69. Gastro-oesophageal reflux VIII E Chan, DK Ng E Chan, DK Ng E Chan, DK Ng DK Ng KL Kwok, DK Ng E Chan, DK Ng E Chan, A Yip E Chan, A Yip, DK Ng A Yip, DK Ng E Chan E Chan, DK Ng L Leung L Leung KL Kwok, Maurice Leung YM Fu, KL Kwok KL Kwok, Maurice Leung KL Kwok 115 116 117 118 119 123 124 125 128 130 131 132 133 140 144 150 152 S Cherk S Cherk 154 157 158 159 MS Choi, S Cherk S Cherk 161 163 CS Ho DK Ng, CS Ho MS Choi KK Chan, S Cherk S Cherk 166 167 169 172 174 TH Fung, S Cherk S Cherk 176 178 TH Fung, S Cherk, CL Yuen CL Yuen, S Cherk TH Fung, S Cherk, CL Yuen LY Wong, S Cherk LY Wong, S Cherk 183 186 189 193 197 PT Yu, L Leung, MC Chan MC Chan 198 199 203 70. 24 hours oesophageal pH monitoring and pH-impedance monitoring (MII-pH) 71. Helicobacter pylori infection 72. Recurrent abdominal pain 73. Cow’s milk protein allergy 74. Management of Idiopathic constipation in children Section 6. Renal system 75. Urinary tract infection in children 2-24 months 76. Monosymptomatic nocturnal enuresis 77. Nephrotic syndrome 78. Fluid and electrolytes therapy 79. Systemic lupus erythematosus 80. Postnatal management of antenatal hydronephrosis 81. Systemic corticosteroids therapy 82. Intravenous cyclophosphamide 83. Formulae related to Nephrology 84. Normal Urine values Section 7. Endocrinology, growth & nutrition 85. Nutritional assessment in children 86. Management of obesity 87. Diabetic ketoacidosis 88. Normal values Section 8. Miscellaneous 89. Management of eczema 90. Infantile scabies 91. Fever of unknown origin 92. Medical management of phimosis using topical corticosteroids 93. Dental service for children 94. Antibiogram 95. Megavitamin Cocktail Regimen 96. Immune Thrombocytopenia (ITP) 97. Haemphilia 98. Management of Haemangioma with Propranolol IX MC Chan 208 MC Chan,WF Lau WF Lau DK Ng MC Chan, L Leung 210 211 213 214 218 219 224 226 230 233 235 238 241 242 245 247 248 250 251 254 256 257 258 259 260 L Leung PH Chan, L Leung L Leung B Pau, L Leung, DK Ng L Leung, A Yuen PH Chan, L Leung E Ho, YY Lam, L Leung L Leung L Leung L Leung YY Lam YY Lam YY Lam YY Lam DK Ng KT Chan, F Poon, DK Ng DK Ng, C Tse MT Soo, DK Ng S Cherk C Tse F Poon KL Kwok, TH Fung, MT Soo, E Chan TH Fung, MT Soo, E Chan KT Chan, L Leung 262 263 265 266 269 274 Section 1. Neonatology Section 1: Neonatology 10 Section 1. Neonatology Chapter 1 - Anaemia in neonates YY Lam Definition: - Hb value less than 12g/dL in the first week or less than 10g/dL later in infancy - Premature infants have slightly lower Hb, higher MCV and reticulocyte counts compared with term infants Causes: Physiological anaemia - Term: Hb unchanged till 3rd week of life trough 11g/dL at 8-12 weeks - Preterm: more profound drop in Hb reaching 7-9g/dL at 4- 8 weeks - Mechanisms: decreased RBC mass / iatrogenic blood loss / shorter life span of RBC / erythropoietin deficiency / rapid body growth Haemorrhagic anaemia - Antenatal: APH (placenta praevia / anomalies of umbilical cord / placental tissue), twin-twin transfusion - Postnatal: fetal-placental haemorrhage, obstetrical trauma - Neonatal: enclosed haemorrhage e.g. cephalhaematoma / ICH / subaponeurotic haemorrhage, coagulation defect: sepsis / congenital lack of coagulation factor / haemorrhagic disease of newborn (Vit K deficiency) / thrombocytopenia Haemolytic anaemia - to be considered if jaundice occurs in the first 24 hours of life - immune / non-immune causes Congenital erythrocyte defect - G6PD deficiency / PK deficiency / thalassaemia / red cell membrane defects Nutritional deficiency - Iron deficiency Systemic diseases - Infection / metabolic diseases / congenital condition (Diamond-Blackfan syndrome) Investigations: Depends on the suspected causes - CBC smear and D/C, reticulocyte count - Direct Coombs test - Kleihauer test - Clotting profile - Sepsis work-up / TORCH studies as indicated 11 Section 1. Neonatology Management: - Treat the underlying cause - Minimise blood taking (in ELBW, document amount of blood loss due to blood taking) - Transfusion dose: 10-20ml/kg of packed cells over 4 hours - Request CMV -ve and leucocyte depleted RBC minipack cells on the request form for preterm babies less than 1.5kg - For babies with PDA, transfusion of packed cells preferably ≤ 10ml/kg over at least 4 hours, if repeated transfusion is indicated, preferably at least 24-48 hours apart. Guidelines for transfusion in preterm neonates 1) Breathing spontaneously - in room-air: T/F if Hb < 7g/dL - with oxygen: T/F if Hb < 8g/dL 2) CPAP - < 28 days: T/F if Hb < 10g/dL - ≥ 28 days: T/F if Hb < 8g/dL 3) IPPV - < 28 days: Hb < 11g/dL if FiO2 < 30% Hb < 12g/dL if FiO2 ≥ 30% - ≥ 28 days: T/F if Hb < 10g/dL Guidelines for transfusion in term neonates Treat underlying causes Stable neonate with Hb 8-10g/dL with no evidence of acute bleeding observe (Likely to be due to chronic / acute-on-chronic fetal-maternal or twin-twin transfusion) Transfusion in patients with symptomatic anaemia or underlying diseases Symptomatic anaemia, e.g. unexplained breathing disorders / unstable vitals / poor growth / diminished activity: - Maintain Hg > 8 g/dL Underlying disease: - Maintain Hct > 13 g/dL for severe cardiopulmonary disease - Maintain Hct > 10 g/dL for moderate cardiopulmonary disease (Severity depends on ventilator settings / FiO2) - Maintain Hct > 10 g/dL for major surgery - In case of severe bleeding with evidence of heart failure single volume ET 12 Section 1. Neonatology Chapter 2 - Congenital syphilis MC Chan Background: - Treponema pallidum: thin, motile spirochaete and extremely fastidious - Majority of infections occur by transplacental passage of Treponema pallidum - Infection by contact with an active genital lesion at time of delivery possible - Risk of transmission in untreated primary syphilis is 70-100%, 40% for early latent and 10% for late latent disease - High risk mother: low socioeconomic levels, HIV mother, poor antenatal care, pregnant women with primary syphilis or illness of unknown duration, higher VDRL titre (>1:16) at treatment or at delivery, < 4 weeks between treatment and delivery, women treated with non-penicillin antibiotics, women received no or inadequate treatment (dose unknown, inadequate, or undocumented) Clinical presentation: - Over 50% infected infants are asymptomatic at time of diagnosis. If not treated, symptoms develop within first 5 weeks of age. - Subtle and non-specific signs in symptomatic infants Early manifestation (< 2 years of age) Late manifestation (> 2 years of age) Skeletal: osteochondritis, periostitis, SGA Skeletal: frontal bossing, short maxilla, saddle nose, scaphoid scapula, painless arthritis of the knees CNS: aseptic meningitis CNS : sensorineural deafness, mental delay, convulsion, paralysis Mucocutaneous: maculopapular rash, palmar / plantar bullae, mucous patches, rhinitis, petechiae, jaundice Mucocutaneous: rhagades, palatal perforation; Hutchinson teeth, mulberry molars Ocular: uveitis, chorioretinitis, glaucoma Ocular: interstitial keratitis, glaucoma, corneal scarring, optic atrophy Renal: nephritis, oedema, ascites GI: hepatosplenomegaly, enteritis, pancreatitis Generalised nontender lymphadenopathy 13 Section 1. Neonatology Classification of Congenital Syphilis: (Adapted from Center for Disease Control and Prevention 2014) 1 Confirmed case T. pallidum is identified by dark microscopy, fluorescent antibody or specific stains in specimens from lesions, placenta, umbilical cord, or autopsy material 2 Probable case 1. Mother with untreated or inadequately treated syphilis at delivery, regardless of signs or symptoms in the infant OR 2. Infant with a reactive treponemal test and any one of the following a. Evidence of congenital syphilis on physical examination b. Evidence of congenital syphilis on long bone x-ray c. Reactive CSF VDRL d. Elevated CSF cell count or protein (without other causes) Inadequate treatment is defined by: - non-penicillin therapy or any therapy (including penicillin) given less than 1month before delivery - undocumented therapy - sub-therapeutic or undocumented treatment response (<4 fold decline in non-treponemal antibody titers after treatment) - inappropriate dose for maternal stage of disease - maternal non-treponemal antibody titers suggest reinfection or relapse (i.e. 4 fold increase) Investigation: Full evaluation for congenital syphilis if mother’s RPR(or VDRL) and FTA-ABS are positive plus one or more of the following conditions: - Syphilis untreated or inadequately treated - Syphilis during pregnancy treated with non-penicillin regime (e.g. erythromycin) - Syphilis treated less than 1 month before delivery - Syphilis during pregnancy treated with penicillin regimen but the expected decrease in RPR (or VDRL) after therapy did not occur - Syphilis treated before pregnancy, but with insufficient serological follow-up to assess the response to treatment and current status N.B. Serum RPR is tested at Kwong Wah Hospital and VDRL is tested at social hygiene clinic, they are different non-treponemal tests and titer can be different for same individual Full investigation of any suspected newborn infants for congenital infection: 1. CBP, D/C, R/LFT, RPR, FTA-ABS, blood culture 2. Cerebrospinal fluid: VDRL, R/M, dark field microscopy, biochemistry and culture 3. Babygram 4. Cranial ultrasound, ophthalmological examination or auditory brain stem evoked potential as clinically indicated in proven or highly probable congenital syphilis 14 Section 1. Neonatology Treatment: (refer to the flowchart) Treatment 1: Penicillin G 50,000 unit/kg/dose (given every 12 hours in the first week of age and then every 8 hours in the second week of age onwards) intravenously for 10 days. (If therapy is missed more than or equal to 24 hours, the entire course must be restarted.) Treatment 2: Benzathine penicillin G 50, 000 unit/kg, IMI, single dose. Isolation procedures: contact precaution for all infants with suspected or proven congenital syphilis until therapy has been given for 24 hours. Follow up: - 3, 6 and 12 months of age for those treated as congenital syphilis - Repeat RPR at 3, 6 and 12 months until it becomes non-reactive or shows a 4 fold decrease - RPR should decline by 3 months of age and should be non-reactive by 6 months if baby is not infected or adequately treated - If RPR is stable or increases after age 6–12 months, the child should be evaluated (including CSF examination) and treated with a 10-day course of parenteral penicillin G. - Congenital neurosyphilis with initially positive CSF VDRL / abnormal CSF should undergo clinical evaluation and repeat CSF examinations at 6 month intervals until normal Retreatment should be considered when - Clinical signs or symptoms of syphilis persist or recur - Sustained 4 fold increase in the titer of RPR - Initially high RPR fails to decrease 4 fold within a year - A reactive CSF VDRL at 6 months - If CSF WBC still abnormal at 2 years or not decreasing - If 24 or more hours of therapy is missed, the entire course must be restarted. Basic evaluation for asymptomatic infants born to mothers who were adequately treated 1. CBP, D/C, R/LFT, RPR, FTA-ABS 2. Further evaluation is warranted for any abnormal result 15 Section 1. Neonatology Algorithm: Reactive maternal RPR/ VDRL Nonreactive maternal treponemal test (i.e.FTA-ABs) False-positive reaction: no further evaluation Reactive maternal treponemal test (i.e. AFB-ABs) Maternal treatment: -None, OR -Undocumented, OR - ≤ 4wk before delivery, OR -Nonpenicillin drug, OR -Maternal evidence of reinfection/ relapse (≥4 fold increase in maternal titers)^ Maternal penicillin treatment during pregnancy AND >4wks before delivery, AND no evidence of maternal reinfection or relapse Adequate maternal treatment before pregnancy with stable low titer (i.e. RPR 1:4 or less or VRDL titer 1:2 or less beyond 1 year after successful treatment), AND infant exam normal Full evaluate Infant physical exam normal; evaluation normal; infant RPR ≤ 4 fold the maternal RPR titer^ Infant physical exam abnormal; OR evaluation abnormal or incomplete; OR infant RPR at least 4 fold greater than maternal RPR titer^ Infant RPR ≤ 4 fold the maternal RPR No evaluation No treatment titer^ or basic evaluation if in doubt Infant physical Infant physical exam normal exam abnormal Infant RPR 4 fold or greater than maternal RPR titer^ infant exam abnormal full evaluation and treatment Basic evaluation; Treatment 2 Treatment 1 Treatment 1 Full evaluation and treatment 1 ^ e.g a titer of 1:64 is fourfold greater than a titer of 1:16, and a titer of 1:4 is fourfold lower than a titer of 1:16 (Ref : CDC 2014, Red Book 2012, Up-to-Date) 16 Section 1. Neonatology Chapter 3 - Feeding regime for Premature and VLBW (<1.5kg) babies YY Lam Principles: Immature gut has - Decreased cell mass and enzyme activity - Disordered/ immature motility - Increased permeability and susceptibility to NEC - Early enteral feeding (trophic feeding) stimulates maturation of gut and improves motility, decreases TPN-related cholestasis, increases gut hormones, decreases risk of catheter-related sepsis and does not increase NEC Importance of human milk in enteral feeding - Improves gut maturation, immunity and normal microbial formation - Protects against NEC (dose dependent effect) Initiation of trophic feeding (Minimal Enteral Nutrition) in VLBW - Start trophic feeding as early as D1 for stable VLBW > 1 kg with no abnormal abdominal signs and symptoms - ELBW babies are usually more unstable: keep NPO during the first few days; trophic feeding can be considered when haemodynamically stable with no inotropic drugs and preferably no UAC in situ - Human milk is preferred; if not available, use premature formula (C20) - Trophic feeding duration and volume ● < 20ml/kg/day during the period of trophic feeding, not counted in the daily fluid ● For ELBW: (<1kg) start with around 10ml/kg/day, can increase gradually to < 20ml/kg/day, for a total of 5-10 days ● For > 1 kg and <1.5kg babies: start with 10-20ml/kg/day for a duration of 3-7 days; start with the lower volume if baby is close to 1 kg Increment of feeding volume after trophic feeding - 10-20ml/kg/day increment, starting with the lower range for the ELBW; the volume will be counted in the daily fluid - If enteral feeding is tolerated well at 100-120ml/kg/day, off TPN/PPN - Add Human Milk Fortifier (HMF) to breast milk if feeding volume is around 100ml/kg/day; increase to 22 Kcal/oz first; keep volume of feeding same after adding HMF for at least 1 day before advancing volume; increase to 24 Kcal/oz if feeding tolerance satisfactory on 22 Kcal/oz for 2-3 days - Full feeding is achieved at around 150ml/kg/day; higher volume or > 24 Kcal/oz formula can be considered in individual case after discussion with neonatologist in charge Monitoring during feeding in VLBW - gastric residue: amount and character - abdominal girth at baseline, then consider measuring regularly 2-4x/day before feed - any abnormal stool Feeding for premature babies ≥1.5kg - for babies <32 weeks and ≥ 1.5 kg follow same regime for <1.5kg - for babies ≥ 32 weeks and < 34 weeks, start with 20ml/kg/day and increase feeding by 20-30ml/day 17 Section 1. Neonatology Residual in gastric aspirate Gastric residue is commonly found in VLBW especially during initial few days of trophic feeding. It may persist longer in ELBW and may appear green initially. < 2ml aspirate can be regarded as physiological if no accompanying abnormal physical findings (see below). Residue usually decreases with increase in feeding, but is seldom > 50% of total enteric feeding if > 50ml/kg/day milk is given, and is usually < 25% of total feeding volume. Assessment and monitoring of the trend is more important than the amount of aspirate. Abnormal physical signs or clinical findings that warrant assessment before continuation of feeding - Abnormal gastric aspirate: bile-stained or bloody - Acute increase in the amount of aspirate in a baby with previously minimal aspirate - Abdominal distension - Abdominal signs: tenderness, erythema or ileus - Bloody stool Withhold feeding and inform doctor if abnormal abdominal signs or residues: Doctors need to be informed for assessing the baby before deciding to resume feeding, augment the feeding regime or proceed to further investigations and management. Supplements of folic acid, vitamins and Ferrum with full enteral feeding Enteral intake recommendations for preterm infants AAP-CON Nutrients (Reasonable nutrient (unit) intake by Tsang)* Folate : 40 (25-50) mcg/kg/day Vit D : 400 IU/day Folate (mcg) Vit D (IU) Nutritional contents in milk# Mature Mature HM + 24 Kcal/oz human 4 pkts premature milk(HM) (Enfamil) formula HMF (Enfamil) unit/dL unit/dL unit/dL 4.8 30 32 Neosure 20 Kcal/oz Enfamil Lipil unit/dL 19 unit/dL 10.8 2 52 41 150 195 Iron : 2-3 mg/kg/day Iron (mg) 0.03 1.44 1.5 1.3 1.22 Vit E : >1.3 (6-12) Vit E (IU) 0.4 5 5.2 2.7 1.35 IU/kg/day # Human milk composition varies; ingredients in formula serve as a reference: composition changes with different brands and needs to be rechecked when accurate calculation is needed * AAP-CON: AAP Committee on Nutrition, Pediatric Nutrition Handbook 2004 Tsang RC: Nutritional Needs of the Premature Infants 2005 Nutritional supplement when full enteral feeding: Folic acid: 0.05mg PO daily until 40 weeks gestation if not on enriched formula Vit D: supply in multivitamin to provide at least 400 units if demand not met in formula, especially in purely breast fed babies Ferrum: until 6 months of age if formula feeding, or 12 months of age if breast feeding, to provide adequate supplement to prevent iron deficiency anaemia; hemolysis can occur if iron is supplemented without adequate vit E, thus give vit E at least 5 IU for preterm on exclusive breast milk feeding with Fe supplement - < 1kg (birth weight): 4mg/kg/day elemental iron - 1-1.5kg (birth weight): 3mg/kg/day elemental iron - 1.5-2.5kg (birth weight): 2mg/kg/day elemental iron - Total supplemented dose depends on the iron supply from milk feeding - Maximal absolute dose 15mg daily 18 Section 1. Neonatology Content in Multivitamin drop (1 ml) : Vit A 1500 IU Vit B1 Vit B2 0.6mg Vit B6 Vit B12 2mcg Vit C Vit D 400 IU Vit E Niacin 8mg 0.5mg 0.4mg 35mg 5 IU 19 Section 1. Neonatology Chapter 4 - Inborn errors of metabolism (A clinical approach) MT Soo, J Wong, DK Ng, F Poon Introduction: Inborn errors of metabolism (IEM) are rare disorders in Hong Kong. The incidence was estimated to be around 1 per 4,000 live births in 2013. In the US, the incidence is estimated to be between 1 in 1,400 and 1 in 5,000 live births. Early diagnosis and treatment of IEM can be life-saving and may sometimes result in full recovery. A high index of suspicion is often required in making the diagnosis. Clinical presentation: IEM can present in various ways, depending on the types of defects, the underlying pathophysiology, age of patient and triggering factors. Based on the pathophysiology, it can be divided into 3 main groups: a) Disorders involving complex molecules: - abnormality of synthesis or degradation of large, complex molecules - present at any age, often after enough time for significant accumulation of substances - permanent progressive organomegaly, bone deformities, organ dysfunction - examples: mucopolysaccharidoses; glycogen storage diseases; gangliosidoses; peroxisomal disorders b) Disorders resulting from intoxication: - damage due to acute or progressive intoxication from accumulation of small molecules such as substrates of deficient enzyme, precursors or metabolites arising from minor pathways - symptom-free interval after birth - present as lethargy, irritability, ataxia, slurred speech, seizures, coma - examples: aminoacidopathies; organic acidaemias; urea cycle defects c) Disorders involving energy metabolism: - deficient production or utilization of energy - symptoms may present right after birth (or even antenatally) - present as failure to thrive, hypoglycaemia, hyperlacticacidaemia, hypotonia, myopathy, cardiomyopathy, ALTE, liver failure - examples: mitochondrial disorders; fatty acid oxidation defects; glycogen storage disorders Clinical Evaluation: - History: Chronicity, age of onset, periodicity, triggers, diet, any similar family history, past history of unexplained deaths or neurologic problems, consanguinity etc - Physical examination: including urine colour and odour ● Dysmorphic features, organomegaly and neurological abnormalities 20 Section 1. Neonatology Basic workup: - Complete blood count with differential count - Urinalysis - Blood gas (Anion gap: Na+ + HCO3- - Cl-, normal range: 12 ± 4) - Serum electrolytes - Blood glucose - Plasma ammonia (send fresh in ice, contact lab before hand) - Urine reducing substances - Urine ketones if acidosis or hypoglycaemia present - Plasma and urine amino acids, quantitative - Urine organic acids - Plasma lactate / pyruvate - Dried blood spot test (contact lab for kit and attend to the collection method) Interpretation: Correct interpretation of the results can help to narrow down the list of differential diagnoses. a. Hyperammonaemia: see Figure 1 Measuring serum ammonia level is always the first step in evaluating patients with IEM especially those presenting with coma. By understanding the differential diagnoses, appropriate measures can help to minimize the toxic effects due to accumulation of ammonia. b. Metabolic acidosis: see Figure 2 c. Lactic acidosis: see Figure 2 d. Hypoglycaemia: see Figure 3 Management: General measures: - Stabilize the patient with appropriate supportive care ● Monitor mental status (ICP) ● Provide adequate calories to prevent catabolism and maintain glucose level above 5.5mmol/L - Removal of toxic compounds or targeted treatment ● Maintain good renal output ● Avoid known precipitant food if any (e.g. galactose, fructose) ● Avoid protein for no more than 1-2 days ● Limit fat intake if fatty acid oxidation is suspected ● Give carnitine empirically if suggestive clinical scenario ● Consider haemodialysis (if hyperammonaemia or renal failure) or exchange transfusion ● Consider cocktails of cofactors and antioxidants (see below) ● Use specific scavengers when appropriate (e.g. for hyperammonaemia, see below) Specific measures: Specific measures depend on the likely diagnosis / group of diagnoses. 21 Section 1. Neonatology Megavitamin Cocktail Regimen: Megavitamin cocktail therapy should be considered in patients who present with an acute severe illness of unknown aetiology in which IEM is highly suspected. This may be in the form of emergencies such as encephalopathy, seizures, liver failure, metabolic acidosis, shock or others. Therapy should be directed to reduce the formation or enhance the secretion of toxic metabolites, provide adequate calories and prevent catabolism, and to provide co-factors empirically if a specific diagnosis is not established. Appropriate immediate treatment improves survival and reduces the chance of neurodevelopmental sequelae. Daily dose Route Availability in KWH Thiamine 50mg IV/PO Formulary drug mitochondrial disorders, MSUD, PDH deficiency, complex I deficiency Riboflavin 100mg 300mg PO Formulary drug glutaric aciduria type I/II, mild variants of ETF, ETF-DH, complex I deficiency (congenital lactic acidosis) Biotin 10mg PO Non-formulary drug multiple carboxylase deficiency (biotinidase, holocarboxylase synthetase) Pyridoxine 100mg IV Formulary drug pyridoxine dependency with seizures, homocystinuria, primary hyperoxaluria type I Vitamin B12 1mg IM/SC/PO Formulary drug methylmalonic academia, homocystinuria Ascorbic acid 100mg/kg PO Formulary drug tyrosinaemia III, transient tyrosinaemia of the newborn, glutathione synthase deficiency, abetalipoproteinaemia 25mg/kg Q6H PO Formulary drug organic acidaemia, carnitine deficiency Co-enzyme Q10 5mg/kg PO Formulary drug respiratory chain defects Pyridoxal phosphate 20mg/kg PO Non-formulary drug PO hereditary orotic aciduria, methionine synthase deficiency, cerebral folate transporter deficiency, Non-formulary drug hereditary folate malabsorption, Kearns-Sayre syndrome Carnitine Folinic acid 20mg Examples of related conditions PNPO deficiency: pyridoxal phosphate responsive seizures For non-formulary drugs, please contact pharmacist on duty and fill in a “non-formulary drug request form”; stock kept in pharmacy for emergency. 22 Section 1. Neonatology Treatment of acute hyperammonaemia: Ammonul (10% sodium phenylacetate and 10% sodium benzoate) intravenous injection is available for the treatment of acute hyperammonaemia, and must be diluted by 1/10 with 10% dextrose to at least 25ml/kg *(Dilution is not fixed for >20kg patient) before infusion via central venous catheter. Arginine HCl injection may be mixed in the same container as Ammonul, and is an essential component of therapy for patients with suspected urea cycle defects e.g. carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS) or argininosuccinate lyase (ASL) deficiency. Loading dose infused over 90-120 minutes should be followed by maintenance infusion over 24 hours. Monitoring of electrolytes is needed because of theoretical risks of hypokalaemia, hypernatraemia and fluid overload. Start extracorporeal detoxification if ammonia > 500 µmol/L - use haemodiafiltration if available; otherwise use haemofiltration or haemodialysis. Contact renal centre if the above treatment is needed. Peritoneal dialysis is not efficient. Exchange transfusion may increase protein and ammonia load, and is considered ineffective. Patients 0 to 20 kg: Patient Population Components of Infusion Solution AMMONUL must be diluted with sterile 10% Dextrose Injection at ≥ 25 mL/Kg before administration. Arginine HCl AMMONUL Injection, 10% Dosage Provided Sodium Phenylacetate Sodium Benzoate Arginine HCl 250 mg/kg 250 mg/kg 200 mg/kg 250 mg/kg 250 mg/kg 600 mg/kg 5.5 g/m2 5.5 g/m2 200 mg/kg 5.5 g/m2 5.5 g/m2 600 mg/kg CPS and OTC Deficiency Dose Loading: over 90 to 120 minutes Maintenance: over 24 hours 2.5mL/kg 2 mL/kg ASS and ASL Deficiency Dose Loading: over 90 to 120 minutes Maintenance: over 24 hours 2.5 mL/kg 6 mL/kg Patients > 20 kg: CPS and OTC Deficiency Dose Loading: over 90 to 120 minutes Maintenance: over 24 hours 55 mL/m2 2 mL/kg ASS and ASL Deficiency Dose Loading: over 90 to 120 minutes 55 mL/m2 Maintenance: over 24 hours Contact on duty pharmacist if the above drugs are needed. 6 mL/kg (Ref : Ammonul (R) drug insert) * For Ammonul infusion: e.g 1) for 20kg child with dose 2.5ml/kg; drug dilute to 10x with D10, final volume 25 ml/kg for infusion. 2) for > 20kg child with BSA 1m2, 55ml/m2, if child weighs 27.5kg, drug given 2ml/kg; dilute 12.5x to final volume of 25 ml/kg, i.e. add at least 632.5ml D10. 23 Section 1. Neonatology (Ref : Image from internet - http://drmhanna.com/urea-cycle-defects/) 24 Section 1. Neonatology Figure 1 Hyperammonaemia (ammonia > 170 µmol/L) Symptoms in first 24hrs of life Preterm Transient hyperammonaemia of newborn Symptoms after first 24hrs of life Full Term IEM Acidosis No acidosis Organic acidaemias ↑ citrulline (>1,000 µmol/L) Citrullinaemia Urea cycle disorders Normal citrulline (50-100 µmol/L) ↑ Arginine ↓ citrulline (undetectable) ↓ Arginine Argininaemia (ARG deficiency) +ve urinary ASA -ve urinary ASA Urinary Orotic Acid +ve Argininosuccinic aciduria (ASL deficiency) Plasma Ornithine Increased HHH Normal Ornithine transcarbamoylase (OTC) deficiency Decreased LPI Key: ASA = Argininosuccinic acid LPI = Lysinuric protein intolerance (reabsorption defect of the dibasic amino acids: lysine, arginine, and ornithine, leading to interruption of urea cycle) HHH = hyperammonaemia-hyperornithinaemia-homocitrullinaemia syndrome (disorder of ornithine transport between cytoplasm and mitochondrion) 25 Carbamyl phosphate synthetase (CPS) deficiency -ve Section 1. Neonatology Figure 2 Metabolic acidosis (pH < 7.3, HCO3 < 15, BE more –ve than -6) Normal Anion Gap e.g. 12 ± 4 Increased Anion Gap e.g. > 16 Abnormal loss of bicarbonate e.g. diarrhoea, renal tubular acidosis Accumulation of fixed acid ↑ β-hydroxybutyrate ↑ acetoacetate ↑ lactate Lactic acidosis Ketoacidosis abnormal a.a. abnormal o.a. Organic acidaemias Rule out acquired causes of ↑lactate e.g. hypoxia, shock, congestive heart failure, liver failure, intoxication e.g. ethanol Primary lactic acidosis normal or ↓pyruvate ↑ lactate/ pyruvate ratio (i.e. >25) ↑ pyruvate normal (15-20) or ↓ lactate/pyruvate ratio (e.g. <10) - Respiratory chain defects - Pyruvate carboxylase deficiency type B Hypoglycaemia Gluconeogenesis defects e.g. - Glycogen storage disease type 1 - Fructose 1,6-diphosphatase deficiency - Phosphenolpyruvate carboxykinase deficiency Hyperglycaemia Normoglycaemia Diabetes mellitus - Pyruvate dehydrogenase deficiency - Pyruvate carboxylase deficiency type A 26 Section 1. Neonatology Figure 3 Hypoglycaemia Rule out severe systemic illness, sepsis, SGA +ve urinary reducing substance -ve urinary reducing substance - Galactosaemia - Tyrosinaemia - Hereditary fructose intolerance check a.a. and o.a. Low urinary ketones Low free fatty acid - Organic acidaemias - Amino acidaemias High urinary ketones ↑ free fatty acid Hepatomegaly? Hyperinsulinism Fatty acid oxidation defects Present ↑ lactate - Glycogen storage disease type 1 - Fructose 1,6-diphosphatase deficiency Absent normal lactate β Consider endocrinopathies e.g. hypopituitarism, hypocortisolism Consider -ketothiolase deficiency Ref : Figures 1-3 reproduced with minor modification from Basic Paediatric Management 3rd edition, Chapter 4 27 Section 1. Neonatology Chapter 5 - Big baby (Macrosomia) YY Lam Definition: > 4,000gm baby or BW > 90th percentile Problems: - Increased risk of shoulder dystocia, birth trauma - Associated with maternal diabetes - Associated with syndromal disorders (e.g. Beckwith-Wiedemann syndrome, Sotos syndrome) Management: P/E: 1. To look for syndromal disorder 1.1 Beckwith-Wiedemann syndrome: macroglossia, linear fissures in lobule of external ear, indentations on posterior rim of helix, large kidneys, hepatomegaly, omphalocoele, hemihypertrophy 1.2 Sotos syndrome: large hands and feet, macrocephaly, prominent forehead, downslanting palpebral fissures, hypertelorism, prognathism and coarse-looking facies 2. Infant of diabetic mothers RDS, polycythaemia, hypocalcaemia, hypoglycaemia Look for congenital anomalies (6-9%) CNS: anencephaly, meningocoele, holoprosencephaly Cardiac: especially hypertrophic cardiomyopathy, conotruncal malformation Skeletal: vertebral and caudal regression syndrome (sacral agenesis) Renal: renal vein thrombosis GI: small left colon syndrome 3. Look for evidence of birth trauma (fracture clavicle, Erb’s palsy) Investigation: Monitor for polycythemia, hypocalcaemia or hypoglycaemia - Monitor H’stix Q1H x 3 or till stable, then Q4H for 1 day - Manage hypoglycaemia accordingly - Check CBP, calcium - X-Ray clavicle (if indicated) 28 Section 1. Neonatology Chapter 6 - Maternal thyroid disorders YY Lam, E Chan Background: - Graves’ disease complicates 1/1,000 pregnancies - PTU, iodine and TSI can cross placenta - Baby may develop goitre, hyperthyroidism or hypothyroidism - PTU may suppress thyroid function in the first few days of life - TSI has a half life of 12 days; delayed hyperthyroidism may occur in 2nd week - Maternal TSI level (if available) can predict occurrence of neonatal hyperthyroidism ( > 5x upper limit suggests high risk of neonatal thyrotoxicosis) - Other risk factors for neonatal thyrotoxicosis include: +ve family history of TSH receptor mutation, mother on anti-thyroid drug or clinically thyrotoxic in 3rd trimester, evidence of foetal thyrotoxicosis. Protocol: - All babies born with maternal thyrotoxicosis should be assessed for neonatal thyroid disease by paediatrician and monitored for related signs and symptoms. - P/E to look for signs and symptoms of hyperthyroidism, hypothyroidism, goitre and upper airway obstruction - Monitor in ward for 24 to 48 hours for any signs and symptoms of hyper- or hypothyroidism (irritability, feeding, heart rate, BP) - Trace cord blood TSH result (screening lab, fax no 27763795), babies with neonatal thyrotoxicosis may have a suppressed TSH. - If result is normal, patient can be discharged home. Babies with abnormal TSH/FT4 (suppressed or elevated) need to be reassessed for fitness for discharge. - If result is not available, baby can be discharged if clinically fit after 24 to 48 hours. - Advise mother / caretaker about signs and symptoms of thyrotoxicosis or hypothyroidism before discharge, so early medical advice can be sought if needed. (Fact sheet available in ward) - 1st follow up between 1-2 weeks of age and repeat TSH and FT4 (KWH lab). If patient has been recalled for TFT from Clinical Genetic Service, trace the result instead of repeating blood test unless baby has signs or symptoms suggestive of abnormal thyroid function. - 2nd follow up at around 2 to 4 weeks with TSH and FT4 repeated - No further follow up if baby is well and results are normal. If abnormal result is found, discuss with endocrine team colleagues for further management. - Ward FU arrangement Thyroid FU arranged at 9:00am BW measured by HCA, check other parameters (e.g. growth parameters, blood pressure, temperature) as clinically indicated and ordered by doctor. Seen by doctor and blood test by phlebotomist afterwards Doctor will review results and examine babies to decide if further follow up needed or case closed. 29 Section 1. Neonatology Figure 1 - Flow chart of management in babies of mothers with thyroid disease Assess babies at risk of thyroid problems, cord blood for TFT sent Observe 24 to 48 hours 1st FU at 7 to 14 days, repeat FT4, TSH, P/E (earlier if high risk) 2nd FU at 14 to 28 days, repeat FT4, TSH, P/E (earlier if high risk) Normal TFT, no FU Abnormal TFT - Consider admission and treatment - Consult Endocrine team 30 Section 1. Neonatology Chapter 7 - Neonatal jaundice B Pau, YY Lam Definition: - Jaundice occurring in the first month of life. Clinical features: - Yellow skin - - Unconjugated: bright yellow - Conjugated: greenish yellow Lethargy Poor feeding Complication of severe jaundice: Kernicterus - Hypotonia, hypertonia, irritability or lethargy - Severe brain damage, athetoid cerebral palsy, deafness or severe MR - Death Causes of NNJ: Early jaundice (especially within 1st 24 hours of life) - Haemolytic disease of newborn (ABO, rhesus, minor blood group incompatibility) - Concealed haemorrhage, polycythaemia - TORCH, syphilis - Sepsis From D3-D4 Non-specific jaundice due to a combination of increased red cell turnover and immature liver conjugation function DDX- Septicaemia Metabolic and liver diseases (esp if prolonged or conjugated) Investigation for severe jaundice (Early and rapid rising or close to ET level): CBP (Non-urgent request if blood group or film review required) Reticulocyte count, blood film Baby’s and mother’s blood group Mother’s blood for anti-A or anti-B Ab (mother Gp O ) Coombs test Trace G6PD level Sepsis screen, CRP Other Ix if clinically indicated: Urine x RS, bilirubin, urobilinogen Thyroid function test (trace Cord blood) Metabolic work up LFT with conjugated and unconjugated bilirubin Hb pattern TORCH Check maternal VDRL/RPR status 31 Section 1. Neonatology Management of NNJ: 1. Treat underlying cause e.g. sepsis 2. General management: ensure adequate hydration, discontinue any medication which may interfere with bilirubin metabolism or binding 3. PT (phototherapy) or ET (exchange transfusion): Refer to the Department NNJ treatment flowchart for GA ≥ 35 weeks 4. Treatment thresholds in Preterms (< 35 wks), Refer to NICE guideline for gestation specific threshold of PT and ET. Print out copy for charting patient’s SB according to time after birth, same GA specific chart to be used till day 14 http://guidance.nice.org.uk/CG98/treatmentthresholdgraph/xls/English 5. Care of babies on phototherapy - Expose as much surface area as possible - Shield baby’s eyes: watch out for conjunctivitis - Monitor baby’s temperature and watch out for hyperthermia - Monitor I/O if indicated and check BW daily - May require addition fluids to compensate for insensible loss, especially for babies on multiple/intensive phototherapy. EBM is the choice for supplementary fluid if available. - Monitor SB: see flow chart 6. Feeding during phototherapy - Enteral feeding including breast feeding is continued. Short interruption for breast feeding or baby care during PT is allowed. - Breast feeding may be stopped during intensive PT. Lactation support to mother should be continued and EBM collected. - If supplementary fluid is clinically indicated, EBM is the choice for supplementary fluid if available. 7. Exchange transfusion: SB level for exchange transfusion, please refer to the Department NNJ treatment flowchart for >/= 35 week and NICE guideline for < 35 week GA babies. Intensive Phototherapy: (Please refer to department protocol for intensive phototherapy for details) Multiple phototherapy and biliblanket with a higher irradiance of the light to be delivered over as much of the body surface as possible. Intensive PT is used to reduce serum bilirubin in cases with severe NNJ that may require ET. For cases admitted with severe NNJ: - Start Intensive Phototherapy & consent for Exchange Transfusion, cross match for ET. - Repeat SB 2 hours later. - If increasing trend or not satisfactory decline, then contact Blood Bank for obtaining blood from Red Cross for exchange transfusion - Repeat SB again 2hrs later (4hrs after Intensive Phototherapy). Proceed to ET if SB still above ET threshold. If SB at presentation is very high or exchange transfusion inevitable (e.g. signs of kernicterus). Immediately contact blood bank to speed up cross match process as well as get blood from Red Cross. Repeat SB when blood is available (maybe within 2 hours) and proceed to ET if SB still above ET threshold. 32 Section 1. Neonatology Exchange Transfusion: Aims: Remove bilirubin Remove haemolytic antibody Correct anaemia (e.g Antenatal anaemia with hydrops) Procedure (Informed consent should be obtained) - Perform in intensive care setting with resuscitation equipment immediately available - Continuous monitoring of baby’s vital signs and ECG monitoring - Use fresh whole blood < 72 hours old - Exchange twice the blood volume i.e. 2 x 80ml/kg - Warm blood during exchange transfusion - Full aseptic technique - Umbilical vein catheterization( if single access, refer to diagram for connection) or arterial line with peripheral vein - OG or NG tube to aspirate all gastric content before procedure and kept in situ during procedure Start exchange with each cycle following the steps below: - draw blood slowly from body – umbilical vein or arterial line - push blood into wastage bag - draw blood from donor pack - slowly inject donor blood into umbilical vein over 1-2 min - wait for ½ min and resume cycle - recording of volume exchanged - each cycle should take > 3 min - aliquot volume should not exceed 10% of estimated blood volume > 2,500gm = 20ml 1,801-2,500gm = 15ml 1,201-1,800gm = 10ml < 1,200gm = 5ml Set up for E.T.: 33 Section 1. Neonatology Complications of ET: - Catheter related o air emboli o aortic or portal vein thrombosis, o haemorrhage from umbilical stump, catheter o NEC - Haemodynamic complications - Hypoglycaemia - Hypocalcaemia: citrate in blood; observe for cardiac arrhythmia on ECG monitor - Hyperkalaemia - Acidaemia - Tissue hypoxia: 2,3-DPG level high in banked blood - Hypernatraemia - Hypothermia Investigations Pre and Post ET: - Can use the 1st and last aliquot drawn from patient Blood for SB, Na, K, Ca, glucose, LFT (conjugated and unconjugated bilirubin), Astrup, CBP (urgent and d/c), blood culture - Consider checking donor blood for Hct, Na, K, Astrup as indicated Prolonged Jaundice: Term > 1/52, Preterm > 2/52 Persistent unconjugated hyperbilirubinaemia (Conjugated bilirubin <15% of total SB) Causes: - Breast milk jaundice (diagnosis by exclusion, ask mother for herbs and drugs history) - Transient familial o Gilbert Syndrome, Criggler-Najjar Syndrome - Haemolytic o ABO, G6PD, Hereditary spherocytosis, Drug induced haemolysis - Intestinal obstruction o Pyloric stenosis, Hirschsprung’s disease - Metabolic o Galactosaemia , Hypothyroidism - Infection o e.g. UTI Conjugated Hyperbilirubinaemia (Conjugated bilirubin >15% of total SB) - Dark urine, pale stool, +/- hepatosplenomegaly Causes: - Neonatal Hepatitis Syndrome - Congenital infection o TORCH o Coxsackie o Varicella Zoster o Listeria, Syphilis - Biliary obstruction o Biliary atresia o Choledochal cyst 34 Section 1. Neonatology - - Acquired infection o Septicaemia / UTI / Meningitis Metabolic o Galactosaemia o Fructosaemia o α1-antitrypsin deficiency o Cystic fibrosis o Tyrosinaemia and other IEM Others – TPN related FU for severe NNJ (Max SB above ET range): - Repeat CBC for late anaemia (2-4 weeks), in cases with significant haemolysis - Screen for hearing (BAER) - Follow up development, watch out for cerebral palsy 35 Section 1. Neonatology SB (μmol/L) Jaundice Treatment Thresholds ( ≥ 38 wks) 450 400 350 300 250 200 150 100 50 0 0 12 SB (μmol/L) 24 36 48 60 72 Age in hours Jaundice treatment Threshold 84 96 108 120 108 120 (35-37+6 wks) 350 300 250 200 150 100 50 0 0 Ref: 12 24 36 48 60 72 Age in hours 84 96 AMERICAN ACADEMY OF PEDIATRICS CLINICAL PRACTICE GUIDELINE Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the Newborn Infant 35 or More weeks of Gestation Pediatrics 2004;114;297 36 37 Routine Care Monitor SB as indicated B Box A Yes No/ only 1 SB available Is SB rising > 8.5 μmol/l/hr? < 24hrs? Yes No Box A Stop PT if SB ≥ 20 below PT. Repeat SB in 12-24 hrs Yes SB Stable or falling? Start Single PT Repeat SB in 12-24hrs SB ≥ PT level but ≤ 30 above line Box A Step down PT or stop PT. Repeat SB in 6-12 hrs Yes No Start Multiple PT Repeat SB in 6-12hrs See Box A Further Ix for NNJ For Intensive PT or ET. Further Ix for NNJ SB < 20 below ET or above ET Yes See Early NNJ Mx Routine Care SB > 30 above PT & > 20 below ET See gestation specific Rx threshold SB < 50 below PT Only 1 reading Repeat SB 4-24 hours later Box B SB ≥ 50 below PT A No Yes Visible Jaundice or elevated TCB Check SB level (excluding early NNJ < 24 hrs) Management of NNJ for infants ≥ 35 wks Section 1. Neonatology 38 Monitor SB until > 24 hrs old. Routine Care if Stable SB. Yes Repeat SB 12 hours later SB below PT A (Infants ≥ 35 wks) Suspected early Jaundice only 1 SB available Box A Stop PT if SB ≥ 30 below PT. Repeat SB in 6-12 hrs Yes SB > 30 above PT & > 30 below ET No Box A See Box A Further Ix for NNJ For Intensive PT or ET. Further Ix for NNJ SB <30 below ET or above ET Yes Step down PT or stop PT. Repeat SB in 4-8 hrs Yes Start Multiple PT Repeat SB in 4-6hrs SB Stable or falling? Start Single PT Repeat SB in 12-24hrs SB ≥ PT level but ≤ 30 above line See gestation specific Rx threshold No/ SB rising > 8.5 μmol/l/hr? Check SB. Identify risk factors and treat accordingly. Management of Early NNJ Section 1. Neonatology Section 1. Neonatology Chapter 8 – Patent ductus arteriosus in preterm infant MC Chan, E Chan, KL Kwok, YY Lam Background: Patent ductus arteriosus (PDA) occurring in about 1/3 infants <30 weeks’ gestation and up to 60% of infants <28 weeks PDA closure can be delayed in preterm infants, and PDA may re-open following constriction when compared with term infants. Clinically significant PDA is associated with increased risk of pulmonary edema, pulmonary haemorrhage, NEC, intraventricular haemorrage, heart failure and BPD. Clinically significant PDA usually develops during first 2 to 3 days after birth. Physical examination in clinically significant PDA: tachycardia, tachypnea, hyperactive precordium, bounding pulse, widened pulse pressure (>25mmHg), systolic murmur, hepatomegaly. Severe PDA: signs of congestive heart failure or decreased cardiac output i.e. shock In premature neonates, clinical symptoms can mimic other diseases e.g. sepsis, RDS; Suspicion of significant PDA should be raised if increased oxygen requirement or failure to decrease ventilator settings. Investigation findings in significant PDA: ECG: LVH +/- LAE CXR: cardiomegaly and pulmonary plethora Echo evidence of haemodynamically significant PDA (≥ 2 features from 1 to 3 or presence of 4) 1. size of PDA (≥ 2mm) 2. LA/Ao ratio (>1.5) 3. PDA shunt flow pattern (growing pattern/ pulsatile pattern)* 4. Absence of antegrade or presence of retrograde flow in diastolic flow in the post-ductal descending aorta (absolute indication) Watch out for evidence of ductal dependent circulation e.g. coarctation of aorta as this may not be evident when a large PDA is present. Consult cardiologist when there is clinical suspicion of aortic lesions * Refer to Arch Dis Child and Fetal Neonatal Edition 1997:77;F36-40 Indication for treatment: 1. For asymptomatic premature newborn < 29 weeks (up to 28 weeks 6 days), early Echo within first 48 hours of life, serial daily monitoring help to check the haemodynamic change associated with PDA and delineate natural course of PDA. Treatment is indicated if with echo evidence of haemodynamically significant PDA. 2. Premature babies with symptoms suspected of significant PDA Fluid management: - Fluid restriction: subtract 30-50ml/kg/day from baseline (minimum fluid usually not less than 60ml/kg/day). Serial clinical and biochemical assessment of hydration status should be done to achieve optimal hydration. Lasix may promote ductal patency by its effects on renal prostaglandin synthesis and should be avoided. - Correction of anemia with blood transfusion, preferably without Lasix - Transfusion of packed cell preferably ≤10ml/kg over at least 4 hours, if repeat transfusion is needed, preferably 24-48 hours apart. 39 Section 1. Neonatology Indication for pharmacological treatment: Treatment indicated in haemodynamically significant PDA, evidenced by clinical or Echo findings. Drug used: Ibuprofen Treatment with Ibuprofen: Consider NPO and start TPN during Ibuprofen Use of sucralfate in case of upper GI bleeding Contraindications: *Impaired renal function (Urea> 14mmol/L, Cr> 140umol/L) Active bleeding (e.g. recent grade III/ IV IVH) Platelet count <60,000/mm3, Coagulation defects Suspected NEC Severe hyperbilirubinaemia (>ET level) Caution with concurrent administration of aminoglycosides (gentamicin): it may result in unexpected elevation of gentamicin level; may consider switching to another group of antibiotics (e.g. cephalosporin or augmentin) if necessary. * in babies with high risk of renal impairment, a lower threshold (Cr >100) may be considered as contraindication. Investigations before start of Ibuprofen: CBP with differential count +/- PT/ APTT RFT, electrolytes, SB USG brain to document any severe IVH Monitoring during Ibuprofen: Urine output (keep > 1ml/kg/hr); if oliguria, consider to withhold and resume when urine output improves and no other contraindications RFT and electrolytes (twice a day) CBP (once daily) Observe for bleeding tendency (i.e. GI bleeding, IVH) BP, pulse pressure, PDA murmur for success or failure of therapy Daily bilateral femoral pulses and upper/ lower BP during PDA treatment Successful closure of PDA with Ibuprofen is about 60-80% (c.f. spontaneous closure rate ~ 30%) Treatment with Ibuprofen (IV or enteral) IV infusion over at least 15 min every 24 hours, preferably undiluted; can add normal saline or D5 to make up the desired volume of infusion. The 2nd course of Ibuprofen can be considered 24 hours to 48 hours after last dose of the 1st course, if PDA remains haemodynamically significant and no contraindications. Oral Ibuprofen (100mg/5ml): Enteral form is preferred, the safety profile is comparable with the conventional IV form; the efficacy of enteral route is comparable with or superior to IV form (70-80% vs 60-70%). Osmolarity of Ibuprofen is ~3900mOsm/kg (KWH preparation Nurofen), dilution with water to 5 times is preferable in order to have reasonable osmolarity and volume. 40 Section 1. Neonatology Dosage: mg/kg/dose mg/kg/dose (24 hours apart) 1st course 2nd course Infusion time 1st 10 10 30min 2nd 5 5 15min 3rd 5 5 15min Use IVI Ibuprofen if: Contraindicated for enteral feeding, e.g. surgical abdomen Patients with high risk of NEC/ gut perforation i.e. severe IUGR, absent end-diastolic flow in AN USG Decision of attending team physician in-charge Side effects: Thrombocytopenia, neutropenia, increased creatinine, hyponatreamia Less common: oliguria, fluid retention, haematuria, intestinal perforation, NEC, IVH, PVL, pulmonary haemorrhage Surgical ligation Surgical ligation if drug closure failed or contraindicated and PDA haemodynamically significant. Other alternative: Paracetamol IV/ PO (after discussion with attending team physician in-charge or on call senior) 15mg/kg/dose Q6H for 3 days (1st course) + 3 days (2nd course) if presence of persistent haemodynamically significant PDA after the 1st course Monitor LFT daily. KWH Oral preparation: Endopain (125mg/5ml); Osmolarity: ~3900mOsm/kg. Dilution with water to 5 times is preferable in order to have reasonable osmolarity and volume. 41 Section 1. Neonatology Chapter 9 - Persistent pulmonary hypertension of neonate (PPHN) M C Chan, E Chan, YY Lam Definition: - Disruption in the normal perinatal foetal-neonatal circulatory transition - Characterized by sustained elevation in pulmonary vascular resistance (PVR) at birth - Leading to R to L shunt via PDA or PFO and decrease pulmonary blood flow Clinical features: - PaO2 < 5-6 kPa in 100% oxygen - Differential cyanosis with more than 10% pre/post-ductal difference in oxygen saturation in the absence of cyanotic heart disease (note: the difference may be less than 10% if shunting occurs mainly in the foramen ovale) Aetiology of PPHN: - Idiopathic (20%), MAS (50%), pneumonia/sepsis (20%), RDS (5%), asphyxia, maternal diabetes, polycythaemia, congenital diaphragmatic hernia - DDx: cyanotic heart disease, severe pulmonary parenchymal disease Investigations: - Blood x glucose, Hct, Ca, Mg, blood gas - Sepsis work-up if indicated - Measurement of pre/post-ductal SaO2 - Echo: to exclude cyanotic heart disease, and to document R to L shunt; estimate pulmonary systolic pressure by measuring TI pressure gradient; assess ventricular function Treatment: 1) Supportive - Correct acidosis, hypoglycaemia, hypothermia, polycythaemia, hypocalcaemia, hypomagnesaemia 2) Ventilation - Consider connecting to ventilator which is compatible with iNO in case iNO is needed - Aim for normocapnia and normal SpO2 - HFOV is beneficial for heterogenous lung disease and in most cases of lung condition leading to PPHN - Sedative +/- paralytic agents may be needed, but use with caution for hypoperfusion (* assess the haemodynamics before use) 3) Haemodynamic support - Initial treatment goals: MBP 50-60 mmHg, systolic BP 60-80 mmHg, subsequent goal adjusted with echo findings and clinical response - Volume support with NS or packed RBC for infants with volume depletion (e.g. haemorrhage) - Adrenaline (inotrope of choice in PPHN) – low dose with β effects i.e. increase cardiac output and HR: 0.05-0.1mcg/kg/min, dose >0.1mcg/kg/min will have additionalα1 effect which leads to increase in BP and peripheral resistance; usual ref range up to 0.2 mcg/kg/min - Dopamine – It can be an alternative to adrenaline or added with adrenaline. Start with 5-10mcg/kg/min to stimulate β receptors to increase myocardial contraction and increase cardiac output. Step up if needed to maximum 20mcg/kg/min. It stimulates α1 receptors which increase arteriolar and venous constriction and increases afterload . 42 Section 1. Neonatology - Hydrocortisone – induces expression of down regulated cardiovascular adrenergic receptors; start together with adrenaline or dopamine at dosage 1mg/kg Q8H Dobutamine – if echo shows poor myocardial contractility Mirilone – use with caution (risk of profound hypotension). Consider in case of poor contractility and high afterload 4) Nitric oxide treatment (iNO) Indication OI > 25 (consider iNO when OI is 15-25, especially in infants who are rapidly deteriorating) in infants ≥35 weeks’ gestational age at birth *The use of iNO in very sick premature infants <35 weeks’ gestational age with PPHN is not well proven to be effective Calculation of OI: MAP (cmH2O) x FiO2%/ PaO2 (mmHg) Example: 20 x 100 / 40 = 50 Conversion of kPa to mmHg = kPa x 7.5 Regime of nitric oxide treatment - Start with 20ppm - The expected response is rapid, occurring in less than 30 min with a PaO2 increase ≥20mmHg.(2.7kPa) - If there is no response, consult senior if higher dose will be considered or nitric oxide is ineffective to be taken off. - Monitor met Hb daily, keep <2.5% - With improvement in oxygenation and after 4-6hours period of stability, start weaning Weaning process: - After oxygenation improves ( ↑PaO2 ≥20mmHg (2.7kPa) and FiO2 can be reduced to 0.6, decrease of OI to ≤ 10), iNO can be reduced to 50% over 4-6hrs as long as OI remains at ≤10 - Repeat the process as above till iNO is reduced to 5ppm - Wean from 5ppm to 1ppm by 1ppm every 2-4 hours - Off iNO from 1ppm with if infant remains well oxygenated in FiO2 <0.6 with PaO2 consistently >50mmHg (6.7kPa) - If deterioration occurs during weaning or after treatment has been discontinued, the dose of iNO should be increased to the previous level or restarted. Once the infant has improved, weaning should be taking place over 24-48hr period - Sildenafil may be added at dose of 0.25-0.5mg/kg PO q 4-8 hours during weaning, especially in cases with iNO dependence 43 Section 1. Neonatology Reference: Inhaled nitric oxide use in newborns; Canadian Paediatric Society; Paediatr Child Health 2012; 17(2):95-7 Algorithm for iNO treatment: Indication: OI >25 AND ≥35wk Consider if OI 15-25 Yes Start iNO = 20ppm for 30min Positive Response - ↑PaO2 ≥2.6kPa Yes No Keep iNO 20ppm for 4-6hr, start to wean FiO2 if well Consult senior to increase or stop Weaning iNO criteria: -OI≤10 OR - ↑PaO2 ≥2.6kPa AND FiO2<0.6 Yes No Keep same dose and back to weaning criteria 24-48hr later ↓iNO 50% over 4-6hr till 5ppm if OI≤10 Yes ↓ 5ppm to 1ppm by 1ppm Q2-4H Fail at any step of weaning Stable Yes FiO2<0.6 AND PaO2>6.7kPa Yes Yes Off iNO Back to previous iNO level or restart iNO 44 Section 1. Neonatology Chapter 10 - Management of neonates with risk factors of early onset neonatal infection MT Soo Early onset neonatal sepsis: - Definition: perinatally acquired bacterial infections in the first 3 days of life - Incidence: ~1-5 per 1,000 live births (i.e. 0.1-0.5%), mortality: ~5-15% Incidence Histologic chorioamnionitis Clinical chorioamnionitis 22 weeks 23 weeks 24 weeks 25 weeks 26 weeks 27 weeks 28 weeks 70% 61% 59% 51% 48% 41% 34% 28% 26% 20% 19% 19% 15% 14% Stoll et al (2010) Pediatrics 126: 443-456 Clinical features: Often non-specific at onset like vomiting, poor feeding, ‘not looking well’etc. Over 90% present with symptoms in the first 24 hours of life, and the rest mostly present before 48 hours Risk factors for neonatal sepsis: 1. Prolonged rupture of membrane (> 18 hours): increases risk 10 fold to 1% Prolonged rupture of membrane (PROM) + prematurity: increases risk to 4-6% PROM + low Apgar score: increases risk to 3-4% 2. Maternal fever or clinical chorioamnionitis*: increases risk to 3-20% (*maternal fever > 38°C with ≥ 2 out of 4: fetal tachycardia, uterine tenderness, foul smelling vaginal discharge, maternal leukocytosis) 3. Maternal GBS carrier + no antibiotic prophylaxis: risk 0.5-1% (vs antibiotic prophylaxis: 0.1-0.2%) + PROM, maternal fever, or prematurity: increases risk to 4-7% + chorioamnionitis: increases risk to 6-20% 4. Prematurity (gestation < 37 weeks): odds ratio for early-onset GBS sepsis 4.8-26.7 5. Maternal UTI 6. Other risk factors: perinatal asphyxia not explained by obstetric cause Online calculator of probability of neonatal early-onset sepsis: http://www.dor.kaiser.org/external/DORExternal/research/InfectionProbabilityCalculator.aspx Investigations and management: Trace Placenta histology for evidence of Chorioamnionitis Asymptomatic infants at risk: CBP D/C, CRP, ± blood culture (especially if preterm labour < 35 weeks); repeat CRP at 12-24 hours Symptomatic infants: CBP D/C, CRP, blood culture and CXR; lumbar puncture if indicated; start antibiotics (see footnote(a) of algorithm below) 45 Section 1. Neonatology Indications for antibiotic treatment: 1. All symptomatic infants 2. Asymptomatic infants at high risk (individual assessment required) Examples of high-risk factors: suspected/confirmed chorioamnionitis maternal high fever ≥ 39oC evidence of bacterial infection in mother e.g. bacteraemia multiple risk factors preterm labour < 35 weeks 3. Patients with abnormal laboratory results: White cell count (term, at birth) < 5 x 109/L or > 30 x 109/L (normal range for white cell count is broad and may not be very useful, unless it is low) Neutropenia: absolute neutrophil count (ANC), at 6-12 hours < 8 x 109/L in term infants or < 2.2 x 109/L in preterm infants Left shift, toxic granulation, I/T (immature/total WBC) ratio > 0.2, or band cells > 2 x 109/L CRP > 10 mg/L Predictive values of adjunctive laboratory tests Sensitivity Specificity Positive predictive value Negative predictive value ANC < 1.75 x 109/L 38-96% 61-92% 20-77% 96-99% I/T ≥ 0.2 90-100% 30-78% 11-51% 99-100% I/T ≥ 0.25 45% 84% 6% 98% I/T ≥ 0.3 35% 89% 7% 98% CRP ≥ 10 mg/L 70-93% 78-94% 7-43% 97-99.5% (Ref:Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin N Am 2004;51:939-959) Lower limits for absolute neutrophil counts at 6-12 hours >36 weeks 28-36 weeks < 28 weeks 9 Manroe 7.8 x 10 /L Mouzinho 2.2 x 109/L 2.2 x 109/L Schelonka (term) 9.5 x 109/L Schmutz 7.5 x 109/L 3.5 x 109/L 1.5 x 109/L (Ref: Polin RA and the Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012;129:1006-1015) Practical considerations for antibiotic treatment: 1. Duration: Antibiotics should be considered to be stopped, usually after 48-72hours, if: - blood investigations (preferably serial CRPs, at least 12 hours apart were normal), - blood cultures, with at least 48 hours incubation, were negative, and - the neonate remains asymptomatic. If sepsis is established, antibiotics can be given for a course, at a minimum period of 5 days; the duration depends on the diagnosis and progress. Caution notes: prolonged initial empirical antibiotic therapy (≥ 5 days) especially in premature infants is associated with increased risk of necrotizing enterocolitis and mortality. (Cotten et al. Pediatrics 2009; 123(1): 58-66, Kuppala et al. J Pediatrics 2011; 159(5): 720-5) 2. Choice of antibiotics: - 1st line: penicillin (preferred in our department) /ampicillin + gentamicin - 2nd line: Augmentin (amoxicillin + clavulanic acid), or Tazocin (tazobactam + piperacillin) to cover pseudomonas or 3rd generation cephalosporin (Claforan), to cover meningitis - 3rd line if indicated: Meropenem (if septic), or vancomycin (for MRSA/MRCONS) 46 Section 1. Neonatology KWH Algorithm for prevention of early onset GBS disease among newborns Yes Admit to neonatal ward Signs of neonatal sepsis? Full diagnostic evaluation Antibiotic therapy No Maternal chorioamnionitis? a b Yes Admit to neonatal ward Limited evaluation No GBS prophylaxis indicated for mother? ce +/- Antibiotic therapy de No f Routine clinical care g Yes Observation in postnatal ward Yes Mother received intravenous penicillin, (routine care) for ≥ 48 hours ampicillin, or cefazolin for ≥4 hours before gh delivery? No ≥ 37 weeks and duration of membrane rupture < 18 hours? Yes Observation in postnatal ward gh (RR/Temp Q8H) for ≥ 48 hours Examination by paediatrician daily during newborn screening exam for 2 days No Admit to neonatal ward, Either < 37 weeks or duration of membrane rupture ≥ 18 hours? Yes CBC, CRP (at birth and at 12-24 hours) +/- blood culture Observation for ≥ 48 hours a Full diagnostic evaluation includes a blood culture, a complete blood count (CBC) including white blood cell differential and platelet counts, CRP, chest radiograph +/- lumbar puncture (only when patient is stable enough to tolerate procedure) b Consultation with obstetric providers is important to determine the level of clinical suspicion for chorioamnionitis. Chorioamnionitis is diagnosed clinically and some of the signs are nonspecific. c Limited evaluation includes CBC with differential and platelets , CRP (at birth and 12-24 hours of life) and blood culture. d Antibiotic therapy should be directed toward the most common causes of neonatal sepsis, including intravenous ampicillin / penicillin for GBS and coverage for other organisms (including Escherichia coli and other gram-negative pathogens) and should take into account local antibiotic resistance patterns. e CBC D/C, CRP at birth and 12-24 hours and observation ≥ 48 hours can be an alternative if the level of clinical suspicion for chorioamnionitis is low e.g. isolated feature of intrapartum fever of mother, fetal tachycardia and baby well after birth. f GBS prophylaxis is indicated if 1 or more of the following is true: (1) mother is GBS-positive within the preceding 5 weeks; (2) GBS status is unknown and there are 1 or more intrapartum risk factors, including <37 weeks’ gestation, rupture of membranes for >18 hours, or temperature of >100.4°F (38.0°C); (3) GBS bacteriuria during current pregnancy; or (4) history of a previous infant with GBS disease. g If signs of sepsis develop, a full diagnostic evaluation should be conducted and antibiotic therapy initiated. h Mother with GBS +ve would be alerted about signs and symptoms of early and later neonatal GBS sepsis and given education pamphlets on discharge. 47 Section 1. Neonatology Chapter 11 – Necrotizing enterocolitis (NEC) MT Soo, YY Lam, E Chan Necrotizing enterocolitis is a disease of multifactorial aetiology leading to inflammation and necrosis of the neonatal intestines, especially in the preterm very-low-birth-weight infants. It may occur singly or in clusters, and the incidence varies among different centers, estimated to be 0.3-2.4 cases in every 1,000 live births, or 2-5% of all NICU admissions, or 5-10% of all VLBW infants. The overall mortality is about 9-28%, but can be up to 45% in VLBW infants. Risk factors: 1. Prematurity (most important: 90% of NEC patients are preterm) 2. Gut ischaemia (likely final common pathway) Conditions that lead to shunting of oxygenated blood from intestine, e.g. maternal use of cocaine, maternal preeclampsia, perinatal asphyxia, polycythaemia, patent ductus arteriosus, cyanotic congenital heart disease, reversed diastolic flow in abdominal aorta, umbilical artery catheter insertion 3. Enteral feeding >90% of patients diagnosed to have NEC have been fed before its onset Decreased risk in those with breast milk feeding Increased risk if feeding increment > 35ml/kg/day and high osmolality of feed (human milk is about 300 mOsm/L; preterm formula, including fortified EBM, should not be more than 400 mOsm/L) 4. Infection Temporal and geographic clustering of outbreak No single infectious agent consistently identified, but increased risk in those with altered gut flora and colonization by potential pathogens Infectious agents include clostridium, gram negative and anaerobic bacteria Clinical features: (Table 1) Management: 1. Prevention Stringent hand hygiene and infection control Early recognition and treatment of correctable factors such as hypoxia, hypothermia, acidosis and hypotension Encourage human milk feeding, and follow standardized feeding regime guideline; caution in feeding of neonates with PDA Probiotics (such as Lactobacillus and Bifidobactirium species) are found to be effective in preventing NEC in premature babies (Cochrane Review 2014). NNT is 29 for babies <1.5kg, but the optimal regimen and duration is not known (In our department, for premature babies < 33 week gestation and > 1 kg, we have experience in using Lactobacillus GG 6 × 109 CFU with milk once daily, from day 4 of life until 36 weeks post-conceptional age, or until discharge, whichever is shorter, for the prophylaxis of NEC. Discuss with the neonatologist in charge when considering probiotics.) 48 Section 1. Neonatology 2. Treatment: (see table below) If there is discordance between clinical and radiological staging, the management should be based on the more advanced one Consult paediatric surgeon for NEC stage IIA or above Suggested empirical antibiotic combination: - ampicillin + gentamicin (or cefotaxime) for both gram +ve and -ve organism coverage - ± metronidazole (for anaerobes) - meropenem (if critically ill, to cover both aerobes and anaerobes) Consider early elective intubation Serial monitoring of infective markers, blood indices and AXR for progress Table 1 : Modified Bell’s Staging Criteria for NEC Stage IA – Suspected NEC Systemic signs Temperature instability, apnoea, bradycardia, lethargy IB – Suspected NEC IIA – Definite NEC Mildly ill Same as above IIB – Definite NEC Moderately ill Same as above, plus mild metabolic acidosis, mild thrombocytopenia IIIA – Advanced NEC Severely ill, Intact bowel Same as IIB, plus hypotension, severe apnoea, combined respiratory and metabolic acidosis, disseminated intravascular coagulation, neutropenia Same as IIIA IIIB – Advanced NEC Severely ill, Perforated Bowel Same as above Intestinal signs Elevated pre-gavage residuals, mild abdominal distension, vomiting, occult blood positive stool Blood from rectum Same as above, plus absent bowel sounds, +/- abdominal tenderness Same as above, plus absent bowel sounds, definite abdominal tenderness, +/abdominal cellulitis or right lower quadrant mass Same as above, plus signs of generalized peritonitis, marked abdominal tenderness and distension Same as IIIA Radiological signs Normal or intestinal dilation. Mild ileus. Treatment NPO for 2-3 days, stop antibiotics after 3-5 days if culture negative Same as above Same as above Intestinal dilation, ileus, pneumatosis intestinalis NPO, antibiotics x 7-10 days, if exam is normal in 24-48 hours. Consult paediatric surgeon. NPO, antibiotics x 14 days, supportive treatment e.g. fluid resuscitation, NaHCO3 for acidosis Consult paediatric surgeon. Same as IIA, plus portal gas, +/- ascites Same as IIB, plus definite ascites Same as above, inotropic agents, ventilation therapy, paracentesis Consult paediatric surgeon. Same as IIB, plus pneumoperitoneum Same as above, plus surgical intervention Consult paediatric surgeon. (Ref : Modified from Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of disease. Curr Probl Pediatr 1987;17(4):243-288) 3. Post-NEC management - Resume small amount of feeding and step up cautiously (around 10-20ml/kg/day) - Continue parenteral nutrition till full feeding established - Watch out for complications: (a) GI: stricture (25-35%), enteric fistulae, short bowel syndrome after surgery (10-20%), malabsorption syndrome, chronic diarrhea, dumping syndrome, fluid and electrolyte loss, hepatitis, cholestasis (b) Metabolic: failure to thrive, metabolic bone disease, increased risk of impaired neurodevelopmental outcome 49 Section 1. Neonatology Chapter 12 - Neonatal parenteral nutrition YY Lam, F Poon Total parenteral nutrition Indications: Unlikely to establish enteral feeding in 1 week (V Yu) Enteral feeding is contraindicated or delivers less than 75% of total protein and energy requirement (Avery) Contraindications: Fulminant sepsis prior to adequate clinical control with antibiotics Uncontrolled acidosis Severe circulatory instability or acute renal failure Intravenous access: Limit dextrose < 12.5% in peripheral vein (V Yu) The solutions to be infused for peripheral parenteral nutrition must have an osmolarity < 900mOsm/L within a pH range of 7.2-7.4 (Culebras) (AAP recommendation) Central line must be used if dextrose > 12.5% is used, amino acid concentration >3.5%, osmolality > 900mOsm/L 20% fat emulsion is isotonic and can be given peripherally Energy: Goal for energy intake in preterm baby is 120 Kcal/kg/day In long-term ventilated infants with CLD, requirement increases by 25-30% (Cairns) (V Yu) BMR of preterm baby is 40 Kcal/kg/day. If an infant is nursed in a thermoneutral environment, an input of 50 Kcal/kg/day is sufficient to match ongoing expenditure but it does not meet additional requirements of growth (Cairns) (V Yu) Resting energy expenditure is 65 Kcal/kg/day The energy cost of gaining 1 gram of new tissue is 5 Kcal. To achieve the equivalent of third trimester intrauterine weight gain of 14-15 gram/kg/day, an additional 70 Kcal/kg/day is required (Cairns) (V Yu) Total fat calories should be 30-40% and < 60% of the diet (Avery) Fluid: Fluid may be adjusted according to serum sodium level in the first week of life. When less than 100ml/kg/day is prescribed, the input of nutrients is reduced proportionally (V Yu). A restrictive early fluid approach significantly reduced the risks of PDA, NEC and death (Cochrane) Glucose: GIR should be started at 4 to 6 mg/kg/min. The glucose infusion may be increased gradually by 1-2 mg/kg/min per day to maximum 14 mg/kg/min if there is no significant hyperglycaemia (serum glucose level > 10 or glycosuria). If still significant hyperglycaemia on TPN with GIR 6 mg/kg/min, may start insulin infusion from 0.01 to 0.1 U/kg/hr and adjust accordingly. 50 Section 1. Neonatology Lipid: Start as soon as possible within first 24-48 hours. Use 20% emulsion in preterm infants as lower plasma triglyceride, cholesterol and phospholipid concentrations than those on 10% (V Yu) (Shulman) (Haumont 1989) - Intravenous lipid must be > 0.5-1 gram/kg/day to prevent essential fatty acid deficiency. If septic or serum bilirubin approaching exchange transfusion level, limit lipid to 2 gram/kg/day. Check triglyceride level after increase in lipid emulsions and after full TPN established increase of lipid emulsion. If triglyceride > 1.7 mmol/L, withhold fat for 1 day and start at a lower dose. When baby is on phototherapy, ensure lipid emulsion is shielded. Suggested regimen of lipid: Start at 0.5-1 gram/kg/day; advance at around 1 gram/kg/day to the maximum of 3 gram/kg/day Amino acids: Start as soon as possible after RCT in sick and premature infants showed that an intake of birth, especially important for 1.5gram/kg/day amino acid from the day of birth in sick, those < 1,250g. premature infants resulted in nitrogen retention and improved protein synthesis (Cairns) (V Yu). Day 1 amino acid also decreased “starvation response” of hyperglycaemia and hyperkalaemia (Adamkin). There are no adverse effects from prompt initiation of PN. It should therefore be started within a few hours of birth. (Ziegler) May use lower dosage in septic or less stable infants. Suggested regimen of amino acids: Start at 1.5-2 gram/kg/day; advance at 0.5-1 gram/kg/day, maximum 3.5 gram/kg/day for term and 4 gram/kg/day for preterm. Electrolytes: Withhold or minimum sodium and potassium in first 1-2 days of life. The dosages are not rigid but depend on the condition and electrolyte balance of the infant. Suggest regimen: i. Sodium: 2-5 mmol/kg/day ii. Potassium: 1-4 mmol/kg/day (Extremely preterm babies have risk of non-oliguric hyperkalaemia from immature distal tubular function) iii. Acetate: Acetate may be given to adjust baby’s acid-base status. Anion in excess of specified Cl can be supplied as acetate. Acetate may be maximized for acidosis or minimized for alkalosis. Be aware that minimizing or maximizing acetate can lead to wide swings in acid-base status. 51 Section 1. Neonatology Calcium and Phosphate: Infant are prone to hypocalcaemia in the first 72 hours due to transient hypoparathyroidism and to hypophosphataemia. Both calcium and phosphate should be added early during TPN therapy. Calcium around 1 mmol/kg/day from birth in preterm babies ≤ 32 weeks to prevent neonatal hypocalcaemia. Adjust clinicaly, preterm around 1-2 mmol/kg/day and term 0.5-1.5 mmol/kg/day The molar ratio of calcium and phosphate should preferably be 1:1 although it can be up to 1.3:1. The exact ratio is governed by the occurrence of precipitation if inorganic phosphate is used. Heparin: 0.5-1 unit/ml must be added to the infusate to reduce the incidence of phlebitis and thrombosis of both peripheral and central venous catheter Useful Reference (from Department web: Prescription Section) Kwong Wah Hospital Neonatal TPN order form Starter TPN order form (Starter TPN can be considered if Pharmacy TPN service is not available) 52 Section 1. Neonatology Chapter 13 - Transpyloric tube feeding in neonate E Chan, YY Lam Indication: Severe gastroesophageal reflux that cannot be adequately managed by other treatments. Complications: Dumping, diarrhea, ischaemic enteritis, duodenal perforation Caution: - Discuss with seniors and preferably in ground round before use. - Not preferred to use in premature babies if <=34wks or <1.8kg - When used in premature babies, you need to execute extreme caution. - Use non-weighted polyurethane enteral feeding tube (Vygon) with appropriate size (<=F8) Estimation of Length of insertion: - 1st mark (distance from mouth or nose to the gastro-oesophageal junction): Identify the lower oesophageal sphincter (LES) based on standard measurement techniques, or use the Strobel formula From nares: (5 + 0.252 x height) cm From incisor: (6.7 + 0.266 x height) cm - 2nd mark (distance from gastro-oesophageal junction to antrum): Distance from the xiphoid process to the right lateral costal margin - 3rd mark (distance from antrum to duodenum): For term baby and infant, further advance the tube for about 5cm Insertion Insert the tube through either nostril or mouth beyond 1st mark Confirm gastric placement by aspiration of acid gastric juice and testing with pH test strip (pH ≤ 5.5) Place patient in a right lateral oblique position with the head of bed elevated 15-30° Advance the tube until resistance is felt at the 2nd mark (at the antrum) For neonate, further advance the tube for about 5cm at 1-2cm every 15 minutes until it reaches the target marking Instill 5-10ml of air until air entry is heard over the RUQ. When the tip is placed in the duodenum, the sounds will be changed from low-pitched gurgles to high-pitched crackles near the right upper quadrant and it will be unable to withdraw air from the tube If the tube is in the duodenum, bile or alkaline fluid may be aspirated Take AXR for confirmation of the position of the tube The ideal position for the tip of the tube is in 3rd or 4th part of the duodenum Feeding regime: slow infusion of milk to decrease dumping, consider monitor BSL initially 53 Section 1. Neonatology Chapter 14 - Surfactant therapy B Pau, YY Lam The primary cause of RDS is inadequate pulmonary surfactant. The structurally immature and surfactant-deficient lung has decreased compliance and a tendency to atelectasis leading to V/Q mismatch, alveolar hypoventilation with resultant hypoxemia and hypercarbia. The use of exogenous surfactant in preterm infants improves oxygenation, decreases air-leak, reduces mortality due to RDS, and decreases overall mortality. Evidence has shown that, in the era of antenatal steroid use and early CPAP, prophylactic surfactant at birth is not superior to early rescue therapy (i.e < 2 hrs after birth). Approach and Surfactant use in infants with suspected RDS: - Early nCPAP at the delivery room should be given to all preterm infants (≤1.5 kg or <32 weeks). - Surfactant therapy should be considered in conjunction with early CPAP if RDS is suspected. - Surfactant is given ASAP (within 2 hrs) for all preterm infants born < 28 weeks or < 1000 grams (if uncertain gestation) - Premature infants <32 week or </=1.5 kg, after initial stabilization at the delivery suite, who requires mechanical ventilation for RDS should receive surfactant. - Early selective use of surfactant in other preterm infants ( ≥28 wks) with RDS who failed nCPAP, defined by at least one of the follows: Failure to maintain SaO2 ≥ 88% despite FIO2 > 0.40 or CPAP > 7 cm H2O Respiratory acidosis (PaCO2 ≥ 60 mm Hg (8 kPa) and pH ≤ 7.2) documented by capillary or arterial blood gases Apnea defined as > 4 episodes of apnea/hr or > 2 episodes of apnea/ hr requiring bag and mask ventilation. Early signs of significant respiratory distress (e.g tachypnea, insucking, grunting) - Discussion with senior if indications besides the above mentioned groups - Consider possible complications (e.g. PPHN, pneumothorax, atelectasis etc) that other management strategies may be needed Surfactant use other than RDS: - Meconium aspiration syndrome requiring mechanical ventilation - Acute RDS secondary to pneumonia which required mechanical ventilation Surfactant Dosage and preparations: - - - Curosurf 2 preparations: 1.5ml vial (120mg phospholipid), 3ml vial (240mg phospholipid) i.e.80mg phospholipid/ml. First dose recommended 200mg/Kg (2.5mls/Kg), dose between 100 to 200 mg/kg has been used especially in milder case or in MIST. It can be considered in prophylactic cases, confirm with senior if with doubt. Subsequent dose 100mg/Kg (1.25ml/kg). Repeat dose (if indicated) 12 hrs later. Survanta 2 Preparations: 4ml vial (100mg phospholipid) / 8ml vial (total 200mg phospholipid i.e. 25mg phospholipid /ml. Dosage 100 mg/Kg (4mls/kg), repeat dose same (if indicated) 12 hrs later MIST (Minimally Invasive Surfactant Treatment) is currently under further investigation and studies, it is only practiced in selected cases with approval or under supervision by neonatal team doctors and should follow pre-defined instructions. Only Curosurf is used when MIST is practiced. 54 Section 1. Neonatology Surfactant Administration - Ensure proper placement and patency of the ETT by auscultation and chest rise ± end tidal CO2. - Hold surfactant in hands a few mins to warm the preparation before use and do not shake. Do not place under radiant heater - Continuous monitoring of vital signs and clinical condition during administration. - Curosurf: Can instil as one aliquot with baby supine and head in neutral position. Ensure that the NG tube used to administer Curosurf is not extending any further beyond the tip of ETT - Survanta: Instil via a closed circuit system using ’trach care’ in-line catheter with minimal disruption to ventilation. Tip of catheter should protrude just beyond the tip of ETT above infant’s carina. Give 4 aliquots as bolus with baby supine and head in neutral position Allow ventilation for 30 seconds in between bolus to allow for stabilization. Slow or stop Survanta administration if deterioration in vital signs or if there is back flow of Survanta up the ETT. - Avoid excessive IPPV in between instillations as inadvertent over-inflation may occur, causing barotrauma. - Consider INSURE approach with surfactant administration (Intubate-SURfactact-Extubate) After surfactant - Stay with the infant after administration as surfactant causes rapid changes in lung mechanics. - Avoid suctioning for at least 1 hour after dosing unless signs of significant airway obstruction occur. - Advanced ventilator settings such as Volume Guarantee modes should be considered in VLBW <1.5Kg. - Pay attention to changes in SpO2 (first to improve), Tidal volume, PV loops, Dynamic compliance (Cdyn usually 0.3-0.5mls/cmH20/Kg in RDS infants, studies suggest good success rate in extubation when Cdyn > 1) - Titrate down FiO2 and ventilation pressures as condition improves. - Early blood gas after surfactant (30 mins) - Target for pCO2 of 45-55mmHg (6 – 7.3 kPa) for babies on mechanical ventilation, provided that the pH is > 7.25 and that significant respiratory distress or recurrent apnoeas are absent. - If the pCO2 is < 40mmHg or > 60mmHg, the baby should be promptly assessed and appropriate action taken. - Consider ‘INSURE’ (INtubate – SURfactant –Extubate to CPAP) technique in preterm babies with mild RDS. Extubate after surfactant to nCPAP or NIV when ventilator requirement is appropriate for extubation and respiratory effort is satisfactory ( FiO2 < 0.3 and MAP < 8 cm H2O) - Consider 2nd dose (12 hours after 1st dose) if baby is still ventilated and requires either: FiO2 >0.3, MAP≥ 8cm H2O or Cdyn < 0.5mls/cmH20/Kg. Discuss with senior if in doubt. 55 Section 1. Neonatology Chapter 15 – Hypoxic-ischaemic encephalopathy B Pau, S Cherk Definition: A hypoxic-ischaemic insult occurring around the time of birth resulting in an encephalopathic state characterized by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. Background: Moderate to severe cases occurs in approximately 2/1000 births. The risk of death or severe handicap in survivors of moderate and severe HIE is approximately 25 and 75% respectively, and children without motor impairments have lower cognitive scores on long term follow‐up. Management strategies include maintaining physiological parameters within the normal range, treating seizures with anticonvulsants and hypothermia therapy. Hypothermia refers to cooling to a core temperature of 33‐34C which is started within six hours of birth and continued for 72 hours. This reduces death and disability at 18 months of age and improves a range of neurodevelopmental outcomes in survivors History and Examination, communication: Document clearly antenatal events, delivery and resuscitation details. Obtain maternal history including significant events during pregnancy. Document discussion with parents in the medical records. Hypothermia therapy Initiate cooling therapy within 6 hours of birth (preferably sooner) for moderate to severe HIE infants ( ≥ 36 completed weeks of gestation) as defined by perinatal AND neurological abnormality criteria (see below). Alert NICU for early preparation if case is identified. Studies have shown that the earlier the cooling is commenced the better the outcome. So far, there is a lack of data to support the use of cooling for neuroprotection in infants of lower gestational age or for other conditions such as sudden postnatal collapse. Babies that fulfilled the perinatal criteria (A) but not the neurological abnormality criteria (B) may also be considered for hypothermia if aEEG is moderately or severely abnormal. The use of hypothermia for all borderline cases should be discussed with senior. Entry Criteria A) Perinatal Criteria (at least one of the following): • Apgar score of ≤ 5 at 10 minutes after birth • Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth • Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial or capillary blood pH <7.00) • Base Deficit ≥ 16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth AND 56 Section 1. Neonatology B) Ongoing Neurological Abnormality entry criteria: Altered state of consciousness (lethargy, stupor or coma) AND at least one of the following: • Hypotonia • abnormal reflexes including oculomotor or pupillary abnormalities • absent or weak suck • clinical seizures Hypothermia procedure: Avoid hyperthermia for HIE babies. Passive cooling can be started, after the initial resuscitation, in cases suspected to have HIE by switching off the radiant warmer. Monitor the temperature closely. Active hypothermia by servo-controlled cooling blanket targeted at 33.5oC rectal temp should be started once criteria A and B as stated above are fulfilled. (All external heat sources must be switched off). At the completion of 72 hours, rewarming gradually by 0.5oC per hour until the rectal temperature is at 36.5oC for one hour. (Refer to Department Guideline “Hypothermia Therapy in Neonate” for the procedure) Discontinue hypothermia if occurrence of serious adverse event requiring therapy: cardiac arrhythmia, persistent acidosis, major thrombosis or bleeding, skin breakdown. Monitoring during Hypothermia: Continuous Core/skin temp, delta Temp, SpO2, AR/RR, ECG and aEEG. Meticulous skin care. Continuous arterial BP monitoring if require ventilatory support or haemodynamically unstable. Monitor urine output (consider indwelling urine catheter), Glasgow Coma Scale Investigations: Baseline CBP/clotting/RFT/LFT/glucose/blood gas/troponin Q6h to Q12 H blood gas/K/glucose Q12 H to daily CBP and clotting, L/RFT Maintaining physiological Parameters Cardio-Respiratory • • • • • • • Avoid hypocapnia (pCO2 <5 kPa) or hypercapnia ( pCO2 >7 ) if ventilated Correct underlying cause for persistent severe metabolic acidosis Maintain SaO2 ≥ 92% to avoid pulmonary hypertension in a term baby Ventilate if incipient respiratory failure with rising FiO2 and pCO2 and pH < 7.25. Obtain arterial access to monitor BP if mechanical ventilation required Aim for the mean BP to be ≥40mmHg in a term baby. Echo, cardiac enzymes, troponin I and ECG (ST elevation) if hypotensive. Consider fluid bolus if hypovolaemia and inotropes if poor contractility. • Bradycardia down to 80-100 common during hypothermia therapy. Perform 12 lead ECG if HR <80. • Consider CVP monitoring via UVC with regular echo assessment of cardiac contractility and stroke volume to guide fluid/inotrope administration • May require hydrocortisone if intractable hypotension, after discussion with senior. 57 Section 1. Neonatology Fluid Balance/Metabolic Management • Fluid restricted to 60 ml/kg/24 hours D10 in first 24 hours. • Aim for neutral fluid balance (Output=Urine output + IWL). • Monitor urinary output closely and maintain ≥1ml/kg/hr. Observe for bladder retention. Insert urinary catheter to monitor urine output if needed. • Ensure adequate intravascular volume before attributing oliguria to SIADH or renal failure. • Consider adding electrolyte supplements or start TPN after 24-48 hours when electrolytes/ renal function stable • Withhold potassium supplementation until urine output is good. • Monitor plasma glucose closely and increases GIR if control suboptimal. • Monitor calcium levels. CNS • Continuous aEEG monitoring until 24hrs after rewarming. • Regular assessment of neurological condition, primitive reflex, pupil size (see HIE staging table). HIE staging (Sarnat and Sarnat, modified by Levene et al) I Clinical Grade Mild II Moderate III Severe Staging Symptoms Hyper-alert, irritable, very reactive to stimulation May be tachycardia, have dilated pupils and jittery Normal EEG, no seizures. Last 3-4 days Lethargic, hypotonic, proximal and central weakness Weak/ absent sucking Low heart rate, small pupils, secretions++ Occasional Apnoea Seizures and abnormal EEG common Last 2-14 days Unresponsive, flaccid Absent reflexes/ absent sucking Seizures common, may be prolonged Abnormal EEG with suppressed background activity Last up to weeks. Outcome Usually normal, may have minor disability 37-54% Death or major disability # 70-86% Death or major disability # # Ref: Cochrane Neonatal Group. Cooling for newborns with hypoxic ischaemic encephalopathy. CochraneDatabase of SystematicReviews 2013, Issue 1.Art.No.:CD003311.DOI: 10.1002/14651858.CD003311.pub3. • The prognosis from the grading schemes should be taken from the maximal worse grade and cannot be used for this purpose before day 3 if the grade is <3. • Watch for the presence of seizures – clinical or on aEEG • Seizures will be missed in heavily sedated and paralysed children and continuous aEEG monitoring is needed • Treat seizures, exclude metabolic derangements. • Refer to chapter on Neonatal seizure on management of seizure. • Anticonvulsants can be discontinued once seizure control has been attained and the infant is neurologically normal (e.g Day 14) 58 Section 1. Neonatology Monitoring for multi-organ failure In addition to Resp/ CVS/ CNS systems: • Haematological: Clotting problem/DIC/thrombosis/ thrombocytopenia • Renal failure: Serial RFTs • Liver failure: LFT +/- ammonia • GI complications: Necrotising enterocolitis. Keep NPO until after rewarmed and not on inotropes. Risk of aspiration if pharyngeal incoordination is present. • Sepsis: empirical antibiotics after sepsis work-up. Classifications of 5 example traces by using the EEG pattern recognition method (right) and voltage method (left) to assess the aEEG background. From Thoresen M, et al. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics. 2010 Jul;126(1):e131-9 Cranial US scan US brain is helpful in monitoring the progress on admission, 7 and 14 days (preferably by a neonatologist/radiologist with experience in neonatal US brain) Pay attention to: • Normal/abnormal anatomical development • Abnormal echogencity/ calcification from the parenchyma (insult predating labour) • Haemorrhage • Swelling, loss of normal tissue differentiation often seen in the first few days. • Increasing white matter echogenicity over time o focal suggesting infarction (stroke) or haemorrhage o more generalised and bilateral suggesting a more global insult • Increasing echogenicity in the basal ganglia and thalami usually bilateral and typical of an acute hypoxic-ischaemic insult. Such changes can be subtle and not be seen before day 7 59 Section 1. Neonatology • • Anterior cerebral or middle cerebral artery doppler. Abnormal if Resistant index < 0.55 on 2-3 occasions within 24- 72 hours from birth (in the absence of large PDA) Typically the RI is normal on day after intrapartum asphyxia and then becomes abnormal on days 2 and 3 before normalising again RI= (peak systolic velocity – end diastolic velocity) peak systolic velocity Follow-up investigations 1. Serial US brain 2. EEG at 24-48 hrs (for all cases): Result of 1st EEG: N/near N Intermediate Abn Severely Abn Second EEG No need 48-72 hr after first EEG 24 hr after stopping hypothermia (to rule out hypothermia effect) 3rd EEG +/- if second EEG before D4 3. MRI brain to be performed between 5 – 14 days post injury • MRI Sequences acquired include T1, T2, diffusion weight imaging (DWI) +/- T2* (for haemosiderin) • DWI performed on Day 5-7 is useful for delineating white matter ischaemia but may underestimate basal ganglia and thalamic injury. • Conventional sequences (T1/T2) performed early may underestimate extent of injury. When performed after 7 days it is helpful for ascertaining the maximum extent of lesions. 4. SSEP at end of first week depending on availability, if not before discharge 5. BAER 6. VEP Prognosis When the results of the follow-up investigations are available (esp MRI and SSEP), arrange joint counselling with O&G, neurologist, +/- MSW/CP. Document full neurological examination before discharge Abnormal aEEG pattern persisting >48 hrs predicts severe disability or death in term asphyxiated infants treated with hypothermia, PPV 80%. All infants who developed sleep wake cycling had a favorable outcome. 60 Section 1. Neonatology EEG Normal EEG good prediction of outcome if done >/=24 hr ( before 1 week) As all EEG improves with time, not reliable if 1st EEG done >1 wk Serial EEG improves prognostic value : -A severely abnormal EEG in first 2 days, if much improvement within 1 week, suggestive of outcome better A study of 23 severe HIE term infants showed inactive EEG pattern in 1st 48 hr life associated with high risk of death. At 1 week, presence of low voltage continuous pattern associated with unfavourable outcome at age 1yr. Persistent abnormalities associated with neurological sequelae (sensitivity 86%, specificity 75%, PPV 67%, NPV 90%) (Ref: E Mariani , Ped Neurolo 2008; 39:317-324) MRI: A study in UK based on a cohort of 175 infants has shown that the pattern of ischaemia on early MRI was a good predictor of outcome at 2 years in different developmental domains. (Ref: M Martinez-Biarge et al. Outcomes after central grey matter injury in term perinatal hypoxic-ischaemic encephalopathy. Early Human Development 86(2010) 675-682.) 61 Section 1. Neonatology Chapter 16 - Brain death in the neonate S Cherk Current knowledge is inadequate to diagnose brain death in neonate less than 7 days old or born prematurely. One or both paediatrcians who will certify brain death should have the skill and knowledge in the diagnosis of brain death. Brain death clinical assessment methods for neonates > 7days: 1) Pre-requisites to be met: - No hypothermia (Core/rectal temp ≥ 35 °C) - No hypotension - No profound abnormality of serum electrolytes, acid base balance or blood glucose - Remediable and reversible condition excluded - No paralytic agent / profound CNS depressant 2) Assessment criteria: 1) document coma 2) document apnoea 3) absence of brain-stem reflexes Examination should remain consistent for brain death throughout the pre-determined period of observation 3) Assessment methods: 1) Coma flaccid tone and absence of spontaneous or induced movements, excluding activity mediated at spinal cord level # lack of response to pain, light or auditory stimuli no eye opening towards painful stimulus to supra-orbital area or nail bed 2) Absence of brain stem function (careful and repeated examinations are necessary) midposition or fully dilated pupil with absent light reflex absent corneal reflex (beware of corneal damage due to other causes e.g. corneal irritation, and eye drops) absent spontaneous oculocephalic (doll’s eye) reflex absent oculo-vestibular response (may be difficult due to small neonatal external ear canals) absent movement of bulbar musculature: ● gag reflex: tracheal stimulation by movement of ETT (repeat several times with observation periods of 10-15 seconds) ● cough, sucking and rooting reflex 3) Absence of respiratory effort with standardized apnoea test pre-oxygenate with 100 % O2 while patient is normally ventilated for 10 minutes disconnect ventilator; 100 % O2 via cannula into endotracheal tube monitor ABG: +ve test if total apnoea when PaCO2 raises to ≥ 60 mmHg 4) EEG electrocerebral silence in the absence of serum phenobarbital level > 25 microgram/ml performed under American EEG Society guideline 62 Section 1. Neonatology 4) Observation period: Two full examinations and EEGs performed 48 hours apart # examples of movement mediated at spinal cord level: - withdrawal - decerebrate posture - complex leg activity 63 Section 1. Neonatology Chapter 17 - Neonatal hypocalcaemia MC Chan, L Leung Definition: Term infant: total serum Ca (tCa) < 2 mmol/L (Avery 2005), ionized Ca (iCa) < 1 mmol/L Preterm infant: total serum Ca < 1.75 mmol/L (taking into account low albumin, acidosis frequently found in these infants), ionized Ca < 1 mmol/L Early onset: typically first few days after birth, lowest at 24-48 hours of age Late onset: end of first week (≥ D7) Symptoms varied and subtle especially in premature infants: irritability, jitteriness, lethargy, poor feeding +/- feeding intolerance, abdominal distension, apnea, cyanosis, seizures. In newborn, Trousseau sign, Chvostek sign and laryngospasm are uncommon. For sick newborns with cardiovascular compromise or organ insufficiency (e.g. BW < 1kg, severe RDS, asphyxia, septic shock, PPHN) requiring BP support, it may be desirable to prevent hypocalcaemia by continuous Ca infusion (4 ml/kg/day), preferably by central catheter to maintain total Ca > 1.75 mmol/L or ionized Ca > 1.0 mmol/L (Manual of Neonatal Care 5th Ed 2004.) Management of early-onset hypocalcaemia in preterms - Severely symptomatic (e.g. seizures): IV 1-2 ml/kg 10% Ca gluconate over 5-10 minutes under ECG monitor in ICU setting. Maintenance IV infusion with 10% Ca gluconate at 4 ml/kg/day. - Asymptomatic well preterms: observe, avoid peripheral Ca infusion, may give oral Ca supplement (usually resolves spontaneously by D3) - If Ca decreases to 1.65 mmol/L: begin continuous Ca infusion: 4-6 ml/kg/day of 10% Ca gluconate (1 mmol/kg/day) IV Ca supplement: treatment risks - Peripheral extravasation → inflammation and subcutaneous necrosis - Rapid Ca infusion can cause sudden elevation of Ca, bradycardia or other dysrhythmias, thus IV Ca should only be “pushed” for hypocalcaemic crisis (e.g. seizures) - If Ca infused through UVC lodged in portal vein, it may cause hepatic necrosis 10% Ca gluconate - 0.22 mmol or 9 mg Ca per ml - pH: 6-8.2; Osmolarity: 700 mOsm/L - Maximum administration rate: 0.045 mmol/kg/hour (or in neonates max. 0.02 mmol/min). May be given more concentrated via a central venous line. Undiluted calcium gluconate can be given in emergency. 64 Section 1. Neonatology Early Neonatal Hypocalcaemia in premature infant tCa < 1.75 mmol/L or iCa < 1.0 mmol/L Severely Symptomatic Asymptomatic IV bolus 10% Ca gluconate (1-2 ml/kg over 5-10 minutes) then IV maintenance (4 ml/kg/day) tCa <or = 1.65 mmol/L To observe +/- oral Ca supplement (1 mmol/kg/day dilute 1:1 with water) continuous Ca infusion (10% Ca gluconate 4-6 ml/kg/day) 65 Section 1. Neonatology Chapter 18 – Neonatal bacterial meningitis MT Soo, C Tse, YY Lam, F Poon Meningitis is present in 10-25% of bacteraemic or fungaemic infants. Up to one third of infants with meningitis have negative blood cultures. The 2010 CDC-GBS guidelines recommend a lumbar puncture in every symptomatic infant with suspected sepsis. In our practice, lumbar puncture is indicated in infants with symptoms / signs suggestive of meningitis, with a positive blood culture, or a high probability of bacterial or fungal sepsis, or who do not respond to conventional antibiotic therapy. In late onset sepsis without a definite focus, LP is indicated. Common causative organisms: - Early onset: Group B Streptococcus (GBS), Escherichia coli, Listeria monocytogenes, herpes simplex virus - Late onset (nosocomial or community acquired): gram negative bacteria Lumbar puncture - contraindications or precautions: - Haemodynamic instability, platelet count < 50 x 109/L, raised intracranial pressure Normal CSF values: No CSF white cell count rules out bacterial meningitis. LP is completely normal in 2-3% of culture proven meningitis. A wide range of normal CSF values is quoted by different sources. > 20 white blood cells/mm3 and/or > 5 polymorphs in a neonatal CSF sample is considered abnormal. Normal CSF should contain predominantly mononuclear cells, if any. Using the ratio of red cell count to white cell count in the peripheral blood to adjust the CSF white cell count in a traumatic tap is controversial. Treatment: 1) Suggested empirical therapy for bacterial meningitis: ampicillin + cefotaxime or high dose penicillin/ampicillin + aminoglycoside or cefotaxime + aminoglycoside, or meropenem ± vancomycin (if resistant gram negative bacteria and MRSA are strongly suspected) Dosages (from Neofax, version Q2-2014): Please refer to updated reference in Neofax regularly. Ampicillin 7 days and younger: 200-300 mg/kg/day IV divided Q8H, 8 days and older: 300 mg/kg/day IV divided Q6H Cefotaxime 50mg/kg/dose (see dosing interval chart 1) Penicillin 7 days and younger: 250,000- 450,000 units/kg/day IV divided Q8H, 8 days and older: 450,000-500,000 units/kg/day IV divided Q6H Gentamicin (see dosing interval chart 2) Meropenem 40mg/kg/dose; less than 32 weeks GA and less than 14 days PNA: Q12H; less than 32 weeks GA and 14 days PNA and older: Q8H; 32 weeks GA and older: Q8H Vancomycin 15mg/kg/dose (see dosing interval 3) 66 Section 1. Neonatology PMA (weeks) ≤ 29 30-36 37-44 ≥ 45 PMA (weeks) ≤ 29 or significant asphyxia, PDA, or treatment with indomethacin 30-34 ≥ 35 PMA (weeks) ≤ 29 30-36 37-44 ≥ 45 Dosing interval chart (1) - Cefotaxime PNA = Postnatal (days) 0-28 > 28 0-14 > 14 0-7 >7 All Dosing interval chart (2) - Gentamicin Postnatal (days) Dose (mg/kg) 0-7 5 8-28 4 ≥ 29 4 0-7 4.5 ≥8 4 All 4 Dosing interval chart (3) - Vancomycin Postnatal (days) 0-14 > 14 0-14 > 14 0-7 >7 All Interval (hours) 12 8 12 8 12 8 6 Interval (hours) 48 36 24 36 24 24 Interval (hours) 18 12 12 8 12 8 6 (Ref : Neofax (electronic resource) accessed via eKG on 18 Jun 2014) 2) Consider to repeat lumbar puncture at 48 hours after initiation of effective treatment, (controversial, not universally practised). Persistence of positive CSF culture may indicate complications e.g. obstructive ventriculitis, subdural empyema, or multiple small vessel thrombi. 3) Indications to repeat lumbar puncture in neonates with - persistent or re-emergent fever - deterioration in clinical condition - new clinical findings (especially neurological findings) - persistently abnormal inflammatory markers 4) In case of persistently positive CSF cultures, or clinical suspicion of neurological complications, perform cranial ultrasound and/or CT brain with contrast. The choice and dosage of antibiotics should be reviewed, and rarely intraventricular administration of antibiotic may be considered. 5) Duration of antibiotic for specific organisms - GBS and Listeria: continue antibiotics for at least 2 weeks; - GBS: high dose penicillin; if on aminoglycoside, discontinue when clinically stable and CSF sterilized - Gram negative bacteria: cefotaxime + aminoglycoside; discontinue aminoglycoside after 2 weeks of CSF sterilization; total duration : at least 3 weeks after CSF sterilization 6) Consider longer duration of therapy under these situations (complicated meningitis): focal neurological signs at 2 weeks, time to CSF sterilization > 72 hours, obstructive ventriculitis, infarct, encephalomalacia, brain abscesses etc. 67 Section 1. Neonatology 7) Watch out for complications - Early complications: seizure, shock, SIADH with electrolyte disturbance, focal neurological signs, hydrocephalus, subdural effusion, ventriculitis, abscess, haemorrhage etc - Late complications: hearing impairment, cortical blindness, persistent hydrocephalus, developmental delay, cerebral palsy, epilepsy etc 68 Section 1. Neonatology Chapter 19 - Paramortem studies for suspected inborn error of metabolism MT Soo, L Leung, Phyllis Leung, KP Chan Specimens should be taken as far as possible within office hours; after-hour lab service regarding muscle biopsy processing may not be guaranteed. Please liaise with lab beforehand. Other useful contact: Chem Lab. Reception Desk, PWH: 26322331 (office hours only) Specimen 1. Clinician’s action and information Transport Test to be done Test done in precautions Blood a. Exactly 1 ml lactate and blood in a pyruvate trichloroacetic acid (TCA) bottle (available in ward); using a pipette for measurement is preferred b. 1 ml blood in ammonia paediatric lithium heparinised bottle c. 3 ml EDTA blood Chemical Pathology Special Lab (6/F, YCKMMC, KWH) Chemical Pathology Lab (5/F, YCKMMC, KWH) send sample to lab in ice send sample to lab in ice carnitine gene PWH Chemical DNA studies or Pathology lab other DNA studies as indicated by other metabolic results Contact KWH Lab action Clinicians should contact Chemical Pathology Lab, KWH If specimen is received outside office hours, centrifuge and separate supernatant, store Office hours (Monday supernatant at -20°C and to Friday: 9 am to 5 pm; send to Chem Lab on the Saturday: 9 am to 1 next working day. pm): 35175140 or 35172447 Outside office hours: 35172464 or 35172489 Clinicians should contact Chemical Pathology Lab, KWH: 35172464 or 35172489 If specimen is received outside office hours, centrifuge and separate plasma, store plasma at -20°C and send to Chem Lab on the next working day. Clinicians will contact Store whole blood at 4°C. on-call biochemist Lab will send to PWH through PWH 26322211 (through G/F Office) on next working day 69 Section 1. Neonatology Specimen Clinician’s action and information Transport Test to be done Test done in precautions amino-acids and PWH Chemical carnitine Pathology lab d. 2 x 3 ml lithium heparinised blood e. 3 ml EDTA blood mitochondrial Cheung Sha DNA analysis - Wan (CSW) a few common Genetics point mutations f. 3-5 ml heparinised blood Chromosomes Cheung Sha study if suspect Wan Genetics dysmorphic syndrome g. Dried blood spot test Broad spectrum screening for metabolic diseases, in particular, aminoaciduria, urea cycle defect, organic acidemia and fatty acid oxidation defect HA hospital pathology laboratories, sent by KWH Chem Path Lab 70 Contact KWH Lab action Clinicians will contact Centrifuge & separate on-call biochemist plasma. Store plasma at through PWH 26322211 -20°C. Lab will send to PWH (through G/F Office) in ice box on next working day. Store any left over plasma at -20°°C in the lab in case more tests are needed for future studies. Clinicians will contact Return specimen to ward if on-call geneticist at received in lab 97261332. Clinicians store blood at 4°C in ward, and send to CSW on next working day through Central Porter Service (clinicians’ clerk will call them to get specimen) Clinicians will contact Return specimen to ward if on-call geneticist at received in lab 97261332. Send immediately through Central Porter Service. If not, clinicians will store blood at 4°C in ward, and send to CSW on next working day through Central Porter Service (clinicians’ clerk will call them to get specimen) Obtain Whatman filter paper from KWH Chem Path Lab (5/F, YCKMMC, KWH): 35172464 or 35172489 Allow spots to dry for at least 3 hours. Deliver to the lab within the same day. If not achievable, keep in room temp, away from sunlight / moisture, and deliver to lab within 3 days. Section 1. Neonatology 2. Clinician’s action and information Transport Specimen Test to be done Test done in precautions Urine: organic acids PWH Chemical Collect as much as and amino acids Pathology lab possible in plain bottle 3. CSF: lactate Collect 300 ul in sterile plain bottle (5 drops), 4. Skin biopsy: Ensure sterile technique, full thickness, put in sterile bottle filled with normal saline skin fibroblast culture for future enzyme essays Chemical Pathology Special Lab (6/F, YCKMMC, KWH) send sample to lab in ice PWH Chemical Transport at Pathology lab room temp Do not freeze 5. Muscle or liver for enzyme Anatomical biopsy or other assays as needed Pathology Lab. tissues requested KWH for freezing procedure (frozen section service is NOT available after office hours) 6. Postmortem specimens: If inadequate blood taken for DNA extraction, blood and spleen tissue can be taken during postmortem. Spleen tissue put in sterile bottle. No need to add normal saline. Anatomical Pathology Lab. KWH Contact Clinicians will contact Dr Nelson Tang at 26322320 or page on-call biochemist through PWH 26322211 Clinicians should contact Chemical Pathology Lab, KWH Office hours (Monday to Friday: 9 am to 5 pm; Saturday: 9 am to 1 pm): 35175140 or 35172447 Outside office hours: 35172464 or 35172489 Clinicians should contact Anatomical Pathology Lab. (35175141) during office hours Outside office hours: 35172464 or 35172489 Clinicians will contact Dr Nelson Tang at 26322320 or page on-call biochemist through PWH 26322211 Clinicians should contact Anatomical Pathology Lab. (35175141) during office hours Outside office hours: 35172464 or 35172489 Staff on duty in Stat Lab. shall put the specimens and request form (wrapped in plastic bags) into -70 °C deep freezer in 5/F upon receipt KWH Lab action Store at -20°C. Lab will send to PWH (through G/F Office) in ice box on next working day. If specimen is received outside office hours, store specimen at -20°C and send to Chem Lab on the next working day. Store any remaining CSF in Chem Lab at -20°C. Lab will store at 4°C. Lab will send to PWH (through G/F Office) on next working day. Staff on duty in Stat Lab. shall notify AP Lab staff to collect back the specimen for examination on the next working day (To be performed by pathologists) 71 Section 1. Neonatology Chapter 20 – Bronchopulmonary dysplasia (BPD) MT Soo, YY Lam Classification of severity of bronchopulmonary dysplasia: Grade 1 Supplemental oxygen for ≥ 28 days AND Mild - On room air at 36 weeks post-menstrual age (PCA) or at discharge (infants < 32 weeks’ gestation) - On room air at 56 days or at discharge (infants ≥ 32 weeks’ gestation) Whichever comes first Grade 2 Supplemental oxygen for ≥ 28 days AND receiving supplemental effective oxygen < 30% at 36 weeks PMA / Moderate discharge (< 32 weeks) or at 56 days / discharge (≥ 32 weeks) Grade 3 Supplemental oxygen for ≥ 28 days AND receiving supplemental effective oxygen ≥ 30%, or on CPAP, or Severe mechanical ventilation at 36 weeks PMA / discharge (< 32 weeks) or at 56 days / discharge (≥ 32 weeks) Modified from Jobe and Bancalari, Am J Respir Crit Care Med 2001;163:1723-1729. Radiographic changes are often present but not required in the definition of BPD. Infants treated with oxygen > 21% and/or positive pressure for non-respiratory disease (e.g. central apnoea or diaphragmatic paralysis) do not have BPD unless they also develop parenchymal lung disorder and exhibit clinical features of respiratory distress. Neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age: BPD Mild Moderate Severe Wt <10th% 49.8% 55.2% 62.6% Growth Ht <10th% 28.9% 37.9% 46.2% HC <10th% 21.7% 27.3% 39.4% % MDI < 70 (mental development index) 25.6% 35.1% 49.8% Rehospitalization for pulmonary causes (OR) 1.16 1.61 2.08 Extracted from Ehrenkranz et al, Pediatrics 2005;116;1353-1360 Prevention of BPD - Avoid intubation, minimize ventilator duration - Careful ventilation strategy, avoid barotrauma and volutrauma; optimal tidal volume 4-6ml/kg; accept pCO2 up to 60 mmHg (8 kPa) with pH >7.2 and SaO2 88-95% for < 34 weeks corrected gestation age - Vitamin A: ELBW (< 1kg), administered at least 3 times per week at 5,000 units IMI for 4 weeks, can decrease the incidence of BPD by 7% (NNT 14) - Caffeine citrate (20 mg/kg loading and 5 mg/kg/day maintenance) started during first 10 days in infants with birth weight 500-1,250g reduced incidence of BPD from 47% to 36% (CAP trial, NNT 9). Improved neurodevelopment outcome at 18-21 months in caffeine group as compared to controlled group is no longer statistically significant at 5 years of age. Caffeine citrate should be considered for those born before 32 weeks’ gestation, on triggered mode ventilation, or with any apnoea. It should be given until at least 1 week after last apnoea, or > 34 weeks corrected gestational age. - Careful fluid, avoid over-hydration 72 Section 1. Neonatology - Systemic steroid reduced the incidence of BPD (caution with associated complications and increased risk of intestinal perforation especially when combined with NSAIDs); long term neurodevelopmental effect e.g. cerebral palsy and decreased head growth, needs to be considered; avoid early use (first 1-2 weeks, especially in the first 96 hours). It may be beneficial in selective groups with a short course and a minimal dose; needs to be balanced with risk and benefit, and thoroughly discussed beforehand. Management of BPD: General: - Optimize growth: may require higher caloric content as much as 125% of standard infant caloric input - Fluid restriction - Attention to oxygenation target and CO2 target Specific: Prevention of hypoxia: - Stringent management of oxygenation with a targeted saturation level i.e. > 90% (in > 34 weeks corrected gestational age) with minimal oxygen support - Higher PaCO2 is generally acceptable (up to 60 mmHg) - Consider oxygen reduction test at 36 weeks corrected gestational age if <30% O2 is used. Oxygen Reduction Test This test may be considered before O2 is taken off for preterm at gestational age of 36 week (36 +/-1 week) who is currently receiving < 30% O2 supplement with SpO2 > 90% and not noted to have desaturation during sleep or feeding by nurses. Part 1: Baseline Duration: 15 minutes 30 minutes after a feeding Monitor HR, RR, SpO2, apnoea, bradycardia (< 80 bpm for > 10 seconds) Record every 60 seconds Part 2: Reduction phase Reduce oxygen by 2% every 5 minutes to room air as tolerated For babies on nasal cannula and O2, reduce flow at rate of 0.5 L/min till flow is 1 L/min and then decrease with rate of 0.1 L/min till flow is 0.1 L/min. O2 concentration is then reduced by 20% every 5 minutes, till in room air and the cannula is off Aim to keep SpO2 90% Monitor the infant every 60 seconds Resume baseline oxygen if apnoea (> 20 seconds), bradycardia (HR < 80 bpm for > 10 seconds) or SpO2 between 80-89% for 5 consecutive minutes or SpO2 < 80% for 15 seconds 73 Section 1. Neonatology Part 3: Room air observation Observe the infants for 30 minutes for adverse outcomes (as stated above) Part 4: Possible outcome Pass: pass all 3 parts, try off-O2 and observe any problems for next 2-3 days, especially during feeding or sleeping Fail: fail either part 2 or part 3 put back on O2 (Extracted and modified from Journal of Perinatology 2003; 23:451-456 and Pediatrics 2004; 114: 1305-1311) Corticosteroids: - Systemic steroid regime (use in those who are ventilator dependent > 2 weeks) (a) “Minidex” regime Dexamethasone iv 0.05mg/kg daily for 10 days then alternate day for 6 days (Yates and Newell, Arch Dis Child Fetal Neonatal Ed 2011; 96(3): F190-4) – total dose 0.65mg/kg Consult the attending neonatologist if considering its use Aim to try extubation after 3 days of steroid; consider to stop steroid after 3 days if failed Give topical/nebulized adrenaline if vocal cord oedema present (b) DART protocol Dexamethasone iv 0.15mg/kg/day for 3 days, 0.1mg/kg/day for 3 days, 0.05mg/kg/day for 2 days, and 0.02mg/kg/day for 2 days – total dose 0.89mg/kg - Ventilated infants receiving inhaled steroids over a prolonged period of time (1-4 weeks) have been shown to be successfully extubated Diuretic: - Evidence does not support the routine use of diuretics, but in some cases these may be indicated and therapeutic goals may be defined e.g. frusemide may improve lung compliance. However, chronic use of diuretics may lead to osteopenia and nephrocalcinosis. These drugs should be taken off if therapeutic goals are not reached. - Rapid-acting diuretics were shown to decrease the invasive ventilator days and oxygen requirement in some studies - Short course diuretic: IV frusemide 0.5-1 mg/kg/day for 3-7 days - Oral diuretics: hydrochlorothiazide 1-2 mg/kg BD + spironolactone 1-3 mg/kg daily Bronchodilator: - May decrease airway resistance - e.g. salbutamol 2 puffs inhaled QID: therapeutic response in the presence of wheeze or increased airway resistance 74 Section 1. Neonatology Investigational treatment and second line medications for refractory cases: (discuss with attending neonatologist first) - Nebulized pentoxifylline for 10 days (days 1-3: 0.25 mg/kg BD; days 4-6: 0.2 mg/kg BD; days 7-8: 0.1 mg/kg BD; days 9-10: 0.1 mg/kg BD; repeat course five days later if needed, until off ventilator and oxygen independent) - Intratracheal budesonide 0.25mg/kg in beractant (Survanta) 4ml/kg (repeat doses every 8 hours until extubation or FiO2 < 0.4) - Inhaled nitric oxide or oral sildenafil if pulmonary hypertension present Immunisation etc: - RSV passive immunization (Palivizumab): 15 mg/kg/dose monthly for 2-5 months (Refer to Indications for HA funding in Chronic Lung Disease; can prescribe as self-financed item if indications not met) - Educate parents on infection control, flu vaccination, hand washing and avoidance of smoking 75 Section 1. Neonatology Chapter 21 - High frequency oscillation DK Ng Indication: Failed conventional ventilation, or routine use for RDS requiring surfactant Frequency: 10-15 Hz Amplitude: Large enough to see vibration of the chest wall Continuous distending pressure: Oscillate the neonate at optimal continuous distending pressure CDP OPT as listed below. 1. Start the CDP same as the mean airway pressure during conventional ventilation and whatever FiO2 to keep SpO2 between 86-92% 2. Determine the opening pressure CDPo by increasing CDP 1-2 cm water every 2-3 minutes. Simultaneously, step down oxygen by 5% as SpO2 goes above 92%. CDPo is achieved when oxygenation no longer improve and / or FiO2 ≤ 25% (mean 20 +/- 4.3 cm water for RDS) or significant haemodynamic compromise occurs 3. Decrease the CDP 1-2 cm water every 2-3 minutes until SpO2 drops below 86% or CDP = 6 cm water. This is the closing pressure CDPc (mean 12 +/- 4.0 cm water for RDS) 4. Recruit the collapsed alveoli again as shown by restoration of SpO2 by stepping up of CDP to CDPo for 2-3 minutes 5. Set down the CDP at CDP OPT = CDPc + 2 cm water (minimum 6 cm water) 6. Mean CDPOPT is 14 +/- 4.0 cm water for RDS 7. 5-10 minutes after surfactant, repeat steps 3 to 5 76 Section 1. Neonatology Chapter 22 – Neonatal narcotic withdrawal YY Lam Drug abuse identified antenatally: Document the substance exposed, dose, last dose Suspicious case: SGA, IUGR, small head, irritability, jitteriness, convulsion Differential diagnoses: hypoglycaemia, hypocalcemia, hypomagnesaemia, sepsis, hyperthyroidism, intracranial bleeding Preliminary investigations: infection screen, RFT, Ca, Mg, urine for toxicology screen (to QEH), +/- TFT, cranial USG Also check maternal HIV, HBV, VDRL +/- HCV status and STD screening Others: Refer MSW +/- CCDS (Comprehensive Child Development Service) Treatment: Supportive Swaddling, holding, reduce light exposure, minimize excessive noise, avoid unnecessary handling Pacifier, frequent diaper changes Hypercaloric formula, small frequent feeds if poor milk tolerance or weight gain If no signs of drug withdrawal, Finnegan score < 8 for 2 to 5 days, can discharge home and FU outpatient for growth, development and social aspects Drug treatment Morphine: use in heroin / methadone abusing mother Preparation: 0.4 mg/mL solution Indications: seizures, poor feeding, diarrhoea and vomiting resulting in excessive weight loss and dehydration, inability to sleep, fever unrelated to infection, or Finnegan neonatal abstinence score ≥ 8 for 3 successive scores Finnegan score Morphine solution (0.4mg/mL) 8-10 0.32 mg/kg/day divided Q4H (i.e. 0.05 mg/kg/dose or 0.13 ml/kg/dose) 11-13 0.48 mg/kg/day divided Q4H (i.e. 0.08 mg/kg/dose or 0.2 ml/kg/dose) 14-16 0.64 mg/kg/day divided Q4H (i.e. 0.1 mg/kg/dose or 0.25 ml/kg/dose) 17 or greater 0.8 mg/kg/day divided Q4H, (i.e. 0.13 mg/kg/dose or 0.33 ml/kg/dose); ↑0.16 mg/kg/day increment until controlled Add phenobarbitone to control irritability if morphine solution > 0.8 mg/kg/day Once an adequate dose is found, and Finnegan score is < 8 for 72 hours, wean by 10% of total dose every 2-3 days If weaning results in score ≥ 8, restart the last effective dose Discontinue morphine when daily dose < 0.12 mg/kg/day (0.02 mg/kg/dose) Discharge when withdrawal score < 8 for 72 hours 77 Section 1. Neonatology Phenobarbitone (Luminal) Loading 10 mg/kg May reload 10 mg/kg Q8-12H (until maximum 40 mg/kg) if 3 consecutive scores ≥ 8 or 2 consecutive scores ≥ 12 Cumulative sum of loading doses Maintenance phenobarbitone (daily dose) 20 mg/kg 5 mg/kg/day 30 mg/kg 6.5 mg/kg/day 40 mg/kg 8 mg/kg/day Check serum phenobarbitone level: Before any additional loading dose beyond 30 mg/kg Before first maintenance dose If symptom score persistently > 8, or < 4 but overly sedated Taper by 10% every days after improvement of symptoms and with mean score <8 for 72 hours on a maintenance dose If use morphine and phenobarbitone together, morphine should be withdrawn first and the infant observed for 2 to 3 days Appendix 1: Neonatal narcotic withdrawal score chart Appendix 2: Flowchart of management of Narcotic Withdrawal Syndrome 78 Section 1. Neonatology Appendix 1: Neonatal Narcotic Withdrawal Score Chart Paediatric Dept, KWH Chart at 2 hours after birth, then Q4H at NICU or Q8H at SCBU if total score ≤ 7, preferably 30 minutes to 1 hour after a feed. If total score ≥ 8, inform doctor. If symptoms severe, consider increase to Q2H in NICU and Q4H in SCBU (step down if stable after 24 hours) Systems Signs and Symptoms CNS High pitched cry Continuous high pitched cry Sleeps<1hr after feeding Sleeps<2 hr after feeding Hyperactive Moro reflex Markedly hyperactive Moro reflex Mild tremors disturbed Moderate/severe tremors disturbed Mild tremors undisturbed Moderate/severe tremors undisturbed Date/ Time Score 2 3 3 2 2 3 1 2 3 4 Increased muscle tone 2 1 3 5 1 1 2 1 1 1 1 2 1 2 1 2 2 3 2 3 Excoriation (specify area:_______) Myoclonic jerks Generalized convulsions Metabolic Vasomotor Respiratory Sweating Fever <39.3oC Fever >39.3oC Frequent yawning (> 3-4 times/interval) Mottling Nasal stuffiness Sneezing (> 3-4 times/interval) Nasal flaring GI RR > 60/min RR > 60/min with insucking Excessive sucking Poor feeding Summary Regurgitation Projectile vomiting Loose stools Watery stool Total score Scorer’s initial Status of therapy (drug / dosage) Guide to assessment and scoring can be found in department web (Ref : Modified from Finnegan Neonatal Drug Withdrawal Scoring System) 79 Section 1. Neonatology Appendix 2 Neonatal Narcotic Withdrawal Score Chart 80 Section 1. Neonatology Chapter 23 – Normal Range of Neonatal Haematological Values MT Soo A. Reference ranges of common coagulation tests Gestational age <28 weeks 28-34 weeks 30-36 weeks Term infants Reference range – PT(s) > 21 > 21 > 16 > 16 95th centile Reference range – aPTT(s) > 64 > 57 > 55 > 55 95th centile Fibrinogen level 0.71-5.35 0.87-4.70 2.25-3.41 1.50-3.73 (5th-95th centile, g/dL) Reference ranges are taken from the Christensen et al paper for neonates <34 weeks gestation and from the Andrew et al paper for those 30-36 weeks’ gestation and term infants. (Ref : Arch Dis Child Fetal Neonatal Ed 2015;100:F270-F274) B. Neutrophil count Normal values (5th centile to 95th centile), from Schmutz (2008) Neutrophil count (x109/l) >36 weeks 28-36 weeks <28 weeks At delivery 3.5-18.0 1.0-10.5 0.5-8.0 Time of peak (hours after birth) 8 hours 6 hours 24 hours At peak 7.5-28.5 3.5-25.0 1.5-41.0 At 72-240 hours (3-10 days) 2.7-13.0 0.8-12.5 1.3-15.3 Neutrophil count during first 72 hours of life of term and near-term (>36 weeks gestation) neonates 81 Section 1. Neonatology Neutrophil count during first 72 hours of life of 28- to 36-week gestation preterm neonates Neutrophil count during first 72 hours of life of <28-week gestation preterm neonates (Ref : Schmutz N et al. Expected ranges for blood neutrophil concentrations of neonates: the Manroe and Mouzinho charts revisited. Journal of Perinatology 2008; 28, 275–281) 82 Section 2. Respiratory system Section 2: Respiratory System 83 Section 2. Respiratory system Chapter 24 - Allergic rhinitis DK Ng Definition: recurrent nasal symptoms of sneezing, discharge, itch and blockage in an atopic child, i.e. concomitant asthma +/- eczema +/- urticaria +/- allergic conjunctivitis with either elevated IgE or positive skin prick test Severity (graded by ARIA guideline) Intermittent < 4 days/week Persistent ≥ 4 days/week or < 4 consecutive weeks and ≥ 4 consecutive weeks Mild: none of the following items are present: Sleep disturbance, Impairment of daily activities, leisure and/or sport, Impairment of school or work, Symptoms present but not troublesome Moderate/severe: one or more of the following items are present: Sleep disturbance, Impairment of daily activities, leisure and/or sport, Impairment of school or work, Troublesome symptoms Differential diagnosis: Subacute rhinosinusitis (headache, decreased smell or taste, halitosis) Foreign body (unilateral) Investigations: -Nasal smear for eosinophil (abnormal if > 4%), +ve skin prick test,↑IgE, Normal sinus X-ray Treatment: - Allergen, irritant avoidance 1.5% NaCl nasal lavage - 2nd generation antihistamine: Cetirizine or loratadine - Intranasal steroids, i.e., for >=2yrs old: fluticasone furoate (Avamys), mometasone (Nasonex); for >=6yrs old: budesonide (Rhinocort aqua) or beclomethasone (Beconase aqua) or ciclesonide (Omnaris) Mild intermittent 2nd generation oral antihistamine PRN (1st 2 rows are the usual preferred treatment) Moderate to severe Moderate to severe Mild persistent intermittent persistent Intranasal corticosteroid + PRN short course Intranasal corticosteroid 2nd generation oral (2-4wks) intranasal or regular 2nd generation antihistamine or corticosteroid H1 blocker montelukast 1st generation oral antihistamine PRN (before sleep) Oral antihistamine PRN Oral antihistamine PRN If poor control, consider sublingual immunotherapy for those sensitive to aeroallergens – contact Respiratory team Please chart allergic rhinitis diary to monitor progress 84 Section 2. Respiratory system Chapter 25 - Bacterial tonsillitis E Chan Symptoms: High fever, sore throat, pain on swallowing. Signs: Tonsils – inflammed with exudate Solitary cervical lymph node with tenderness Hoarseness If there is respiratory distress, consider other diagnoses Test: Throat swab for culture, rapid test if available, other test - Blood for ASOT Treatment: Antipyretics + hydration Penicillin V 30 mg/kg/dose PO BD, max 1 gram BD for 10 days if suspected / confirmed bacterial (GAS) tonsillitis Complications: Rheumatic fever, post streptococcal glomerulonephritis, quinsy, retropharyngeal abscess Retropharyngeal abscess Symptoms: very poor feeding, toxic, stridor, marked neck swelling, pharyngeal swelling, torticollis Organisms: Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, Bacteroides, Peptostreptococcus, Fusobacterium, Streptococcus milleri Investigations: Pre-vertebral soft tissue shadow by lateral neck Xray: > 7 mm at C2 or > 14 mm at C6 for children, > 22 mm at C6 for adult suggestive of retropharyngeal abscess. CT neck with contrast is done for confirmation, although differentiation between retropharyngeal abscess and retropharyngeal cellulitis can be difficult at times. Need to seek surgical opinion. Antibiotic: Clindamycin (broader coverage for anaerobe), and Amoxycillin / clavulanate (better gram negative coverage) 85 Section 2. Respiratory system Chapter 26 - Common cold (URI) E Chan, DK Ng Common cold – a short, usually mild illness in which upper respiratory and nasal symptoms, such as runny nose, are the most frequent (the so-called Kleenex sign). Diagnosis: If there is respiratory distress, this is not common cold. For patients with a relative long history of cough and runny nose, consider other causes like allergic rhinitis, subacute rhinosinusitis. Investigations: Consider CBC and CXR if other differential diagnosis strongly suspected Causes: Rhinoviruses & RSV account for the majority of common colds Others – influenza A, B; adenovirus; parainfluenza; RSV; enterovirus; coronavirus; C. pneumoniae; M. pneumoniae; pneumococcus; H. influenzae; M. catarrhalis Treatment: 1. Antipyretics – paracetamol 10-15 mg/kg/dose Q4H PRN if temp ≥ 38.5°C and no more than 60 mg/kg/day 2. Adequate hydration 3. Nasal drops – infants and young children: 0.9% NaCl nasal drops for nasal blockage 4. Nasal decongestant – i.e. 0.5% Ephedrine nasal drops, not recommended for use in young children with the common cold. It is moderately effective for the short term relief in adults, while there is no evidence available to show benefit after repeated use over several days. 5. Antihistamine – chlorpheniramine – caution in < 2 years old, 2-5 years old 1 mg tds, 6-11 years old 2 mg tds (not > 12 mg/day). Beware of CNS depression and thickening of bronchial secretion. 6. Cough suppressant – not recommended 86 Section 2. Respiratory system Chapter 27 - Childhood pneumonia E Chan Definition: Infection of the lung parenchyma Diagnosis: Clinical presentation: fever, tachypnoea, respiratory distress, ↓ chest expansion, percussion dullness, bronchial breath sound, crackles, ↑ vocal resonance CXR: Air space consolidation: homogeneous opacities of lung parenchyma; or interstitial infiltrate or both. Severity (for 28d – 59m old) Very severe: not able to drink, central cyanosis (consult PICU) Severe: lower chest in-drawing Moderate severe: >50 breaths/min (age 2-11m), >40 breaths /min (age 12-59m) Diagnostic specimens: Sputum culture (induced or otherwise) – specimen not appropriate for culture if WBC<10 per low power field and squamous epithelial CELL >25 per low power field Induced sputum (by nebulized normal saline or hypertonic saline as required) NPA for viral immunofluorescence/PCR Blood culture (positive yield < 2.7%), indicated in cases that require IVI antibiotic CBP/DC and CRP BAL if not responsive to treatment, recurrent pneumonia, suspected unusual organisms, suspected aspiration Common causative agents and initial treatment: Birth to D20: GBS, gram negative enteric bacteria, Listeria monocytogenes, TORCH (usually part of systemic infection) Treatment: i.v. penicillin and gentamicin or augmentin and gentamicin 3 weeks to 3 months: RSV, parainfluenza, Chlamydia trachomatis, pneumococcus, Staphylococcus aureus, Bordetella pertussis Treatment: If afebrile, oral azithromycin 10mg/kg daily for 5 days (cover for pertussis) If febrile or in distress, add i.v. augmentin (5:1) 30 mg /kg q12 h, i.e. amoxicillin 25mg/kg/dose, or cefotaxime 4 months to 4 years: Usually viral (RSV, influenza, parainfluenza, adenovirus, rhinovirus), Treatment: Likely viral cause: supportive treatment Likely bacterial (most likely pneumococcus, non-typable H influenza, M.Catarrhalis ). If not ill, oral augmentin (Table 1). If ill, i.v. augmentin (5:1) at 90 mg/kg/day, i.e. amoxicillin 75mg/kg/day+clavulante 15mg/kg/day 87 Section 2. Respiratory system Table 1: Oral augmentin regime for pneumonia in children >=3 months `Pathogens Empirical Strep. pneumoniae Haemophilus infuenzae Moraxella Catarrhalis Augmentin preparation 475mg/5ml(7:1) Amoxicillin (Max.1,750mg) 90mg/kg/day (TDS) Amoxil alone at 90mg/kg/day TDS 40mg/kg/day BD 40mg/kg/day BD Clavulanate(max. 250mg) 12.9mg/kg/day 6.4mg/kg/day 6.4mg/kg/day Use of mega-dose penicillin in pneumococcal pneumoniae The MIC for resistant pneumoccus (non-meningitis) is different between PO (<2) and IV (<8) penicillin meaning high dose IV penicillin can be prescribed to overcome PO amoxil treatment failure. [high dose IVI penicillin 300,000unit/kg/day (divided into 4-6doses; adult: 3 million units Q4H) or IVI ampicillin 300mg/kg/day (divided into 4-6doses)] 5 to 15 years: Walking pneumonia-most likely Mycoplasma pneumonia, Chlamydia pneumoniae Pneumonia with systemic inflammatory response syndromeStreptococcus pneumoniae, H. influenza, M. catarrhalis Treatment for walking pneumoniae : oral Azithromycin 10mg/kg/day for 3 days (max: 500mg per dose) Note: watch out for co-morbid bacterial infection and/or macrolide resistant moderate/severe mycoplasma; observe clinical response accordingly, if required, get relevant sample for culture, mycoplasma PCR study for resistant strain (need special arrangement with microbiologist/DH); Treatment for pneumonia with SIRS: add i.v. augmentin for ill patients. For macrolide resistant moderate/severe mycoplasma pneumonia, quinolone or doxycycline (for>8 years old, 2.2mg/kg/dose BD, up to 100mg BD) Duration of treatment = usually 10 days in uncomplicated cases FU for clinical resolution +/- CXR resolution Recurrent pneumonia: > 2 episodes of pneumonia in 1 year or > 2 in any time frame Refer to respiratory team for further investigations 88 Section 2. Respiratory system Chapter 28 - Chronic cough E Chan, DK Ng Definition: cough lasting for > 3 weeks. Causes: active or passive smoking, asthma, gastroesophageal reflux, post nasal drip, habit cough, foreign body aspiration, congenital lung anomalies, tic Infancy Early childhood Post viral GERD Asthma Infection Persistent bacterial bronchitis Congenital malformation GERD Congenital heart disease Passive smoking Passive smoking UACS(PND) Environmental pollution Foreign body Asthma Bronchiectasis Chronic cough can be due to multiple causes Late childhood Asthma UACS(PND) Smoking TB Bronchiectasis GERD Habit cough Tic History Look for characteristics of cough, environmental factors, other associated symptoms, family history, and history of exposure to infectious disease, drug history 1. Nocturnal cough, precipitated by cold air, exercise, aerosols – asthma 56% positive predictive value (ppv) 2. Throat clearing, nasal discharge, previous sinusitis – post nasal drip or upper airway cough syndrome 52% ppv 3. Dyspepsia, cough worse after meals – GERD 40% ppv Most important environmental factors – smoking or passive smoking History of wheeze, family history or personal history of atopy – likely asthma Mostly wet cough: think of Persistent bacterial bronchitis (PBB: +ve sputum culture and normal CXR), bronchiectasis Any history of TB / sick contact Upper airway cough syndrome(UACS): Cough due to upper airway irritation by post nasal drip (PND) GERD Investigations** Drug – any ACEI Depend on history and physical exam May need multiple / sequential investigations to find causes of cough Treatment Treat accordingly If cough not resolved, check compliance to medication, review diagnosis from time to time. Beware of multiple causes of cough that mandate simultaneous treatment ** refer to flow chart 89 Section 2. Respiratory system Chronic cough, avoid passive smoking History, physical exam, spirometry, CXR with BD challenge Suspected underlying airway/ear pathology Observe x total cough duration of 10 weeks No Cough > 10 weeks or severe cough Yes Investigate and treat accordingly No Yes Recent viral illness Resolve No Yes Resolve No No Yes Manage accordingly Nasal smear x eosinophils CBP D/C, IgE, skin test, FeNO Airway resistance (IOS) Spirometry with challenge (exercise if history of exercise intolerance/ otherwise methacholine or mannitol); bronchodilator response PFR/FEV1 diurnal variability Induced sputum x eosinophil, neutrophil, C/ST Empirical Rx Resolve Abnormal tests Treat accordingly No Likely asthma / allergic rhinitis/ PBB / Habit cough Yes Yes Resp clinic Investigations (individualized clinically) Investigation for atopy / infection 24 hour pH study / OGD impedance / CT paranasal sinuses Bronchoscopy / VFSS Repeat CXR / HRCT thorax Mantoux test If abnormal Treat accordingly No Co-morbid psychosocial conditions Yes Tests normal No suspicious organic causes No Yes Refer CP or MSW For case conference No Resolve Yes Cure 90 Section 2. Respiratory system Chapter 29 - Acute asthma E Chan, DK Ng Initial assessment of severity Speech Alertness Accessory muscles and suprasternal retractions SpO2% (in room air) Mild Moderate Severe Sentences May be agitated Phrases only Usually agitated Words only Usually agitated Usually not Usually Usually > 95% 91-95% < 90% Respiratory arrest imminent Drowsy or confused Paradoxical chest wall movement Continuous bronchodilator Contact senior/PICU immediately treatment and Management Continuous neb steroids Give steroids Consider PICU admission Hypercapnia (hypoventilation) develops more readily in young children than in adults and adolescents. Inhaled bronchodilator x 3, Consider systemic steroids for those on ICS For tracking of progress of asthma Clinical Asthma Score (Ref : Van Der Windt DA, Nagelkerke AF, Bouter LM, et al. Clinical scores for acute asthma in pre-school children: a review of the literature. J Clin Epidemiol 1994;47:635-646) Score= 0 Score= 1 Score= 2 Absent or Mild Moderate Severe Respiratory Rate 24 to 36 months <35 35-55 >55 3 to 6 years <30 30-50 >50 > 6 years <20 20-40 >40 O2 Requirement to keep sat ≥ 93% FiO2 0.21 0.22-0.35 >0.35 18 to 35 months LPM- N/C 0 >2 ≤2 FiO2 0.21 0.22-0.35 >0.35 3 to 6 years LPM- N/C 0 >3 ≤3 FiO2 0.21 0.22-0.35 >0.35 > 6 years LPM- N/C 0 >4 ≤4 Mild Moderate Severe Dyspnoea Mild Moderate Severe WOB Mild Moderate Severe Wheezing Mild Moderate Severe Cough Total (out of 12) 91 Section 2. Respiratory system Dyspnea Mild (Score =0) Toddler normal speech Child speaks in complete sentences Wheezing Mild (Score =0) Breath sounds clear or coarse with good air entry Moderate (Score =1) Toddler crying Child speaks in phrases or partial sentences Moderate (Score =1) Inspiratory and/or expiratory wheeze Absent wheeze but moderate dyspnea and/or work of breathing Mildly decreased air entry Severe (Score =2) Toddler no cyring Child speaks in single words or short phrases Severe (Score =2) Breath sounds nearly inaudible Air entry markedly decreased Absent wheeze but severe dyspnea and/or work of breathing Work of Breathing Mild (Score =0) No retractions or mild intercostal retractions Cough Mild (Score =0) No or mild cough. Moderate (Score =1) Moderate intercostal retractions Moderate accessory muscle use ± Nasal flaring Moderate (Score =1) Frequent dry, tight, or hacky cough without loss of breath Severe (Score =2) Severe intercostal retractions Severe accessory muscle use Nasal flaring Severe (Score =2) Frequent dry, tight, or hacky cough with loss of breath CAS Initial Treatment Guide >8= Contact senior/PICU immediately Continuous neb Give steroids 6-8 = Continuous bronchodilator treatment and steroids Consider PICU admission 4-5 = Inhaled bronchodilator q 20 min x 3, Give steroids 2-3 = Inhaled bronchodilator q 30 min x 2, Consider steroids 0-1 = Inhaled bronchodilator x1 92 Section 2. Respiratory system MDI Salbutamol – Using pMDI + spacer provides equivalent bronchodilatation with a more rapid onset and fewer side effects compared to nebulizedβ2-agonists Dosage: 8 puffs (up to 12 puffs can be given) Q15min to Q4H depending on severity Ipratropium bromide – Use with B2 agonist – Dosage: 4 puffs Q6H Corticosteroids – Should be given in moderate to severe cases – Prednisolone 1-2 mg/kg/day in single or 2 divided doses for 3-5 days (50 mg /day max) – iv methylprednisolone 1 mg/kg Q6H (max 40mg/day) for 2 days followed by prednisolone for 3 days – Oral preparation is as effective as parenteral route – Early concomitant use of inhaled corticosteroid provide an earlier steroid effect Leukotriene Modifiers In severe attack, continuous nebulized salbutamol • Dosage: 0.5 mg/kg/hour (up to ~10mg over 1 hr) • 0.1% nebulized salbutamol solution = 1 mg/ml • Option 1. Consider put on CPAP/NIV if not intubated, give the neb via the in-limb of ventilator circuit; ultrasonic nebulizing device via in-limb of ventilator circuit; output: 12ml/hr, ie, for a 30kg child, 10mg salbutamol (10ml) + 2ml normal saline (instill 3ml into the device and infuse med at 12ml/hour into the device by syringe pump) • Option 2. Continuous Neb via Vent-stream nebulizer (7-8 L/m), output: 20ml/hr, ie, for a 10kg child, 5mg salbutamol (5ml) + 15ml normal saline (instill 5ml into vent stream device and infuse med at 20ml/hr into the device by syringe pump) IVI Magnesium sulphate – Potent bronchodilator acting on the bronchial smooth muscle – Used in severe cases and in PICU – Dosage: (50) mg/kg (max 2 gram) infusion over 20 mins followed by 30mg/kg /hour to keep serum Mg level 1.5-2.5 mmol/L. 93 Section 2. Respiratory system – Under PICU monitoring • 49.3% MgSO4 = 2,470 mg / 5 ml vial • diluted with D5 or H2O 60mg/ml (max conc. 200 mg/ml) infused over 20 minutes, max 125 mg/kg/hour e.g. 15kg pt: prescribe 600mg MgSO4 IVI over 20 mins (dilution: 49.3% MgSO4 4ml + 29ml D5 = 59.9mg/ml) infuse 10ml over 20 min Avoid anti-histamines Mucolytic drugs have no established role Chest physiotherapy has no proven value Antibiotic only if there is strong evidence to suggest bacterial infection Use of CPAP & Non-invasive ventilation Start with CPAP of 5 cmH2O, clinically check for expiratory breath sound and wheeze; gradually titrate up CPAP to attain good expiratory breath sound and decrease loud wheeze (from experience, up to 7-10cmH2O for kids, 10-12cmH2O for teenagers) If poor response intubate electively by flexible bronchoscope with Ketamine sedation. If bronchoscopy is not available, intubate with Ketamine/Suxamethonium +/- Atropine & micro-cuff ET tube. If plastic bronchilitis is seen, remove with 0.9% NaCl / 8.4% NaHCO3 (ratio 4:1). Chest compression is often necessary to remove air trapping after intubation. To reduce air trapping, pre-oxygenate, disconnet from ventilator circuit for 30-60 seconds hourly with firm chest compression. Pre-discharge planning: Acute asthma pre-discharge planning 1. 2. 3. 4. 5. 6. 7. 8. Grading of severity of asthma by clinical features and spirometry and start preventive medications as per current protocol Perform SPT if not done before to confirm atopy Look for other concomitant atopic diseases and treat accordingly Started inhaled corticosteroid if patient requires systemic corticosteroid during admission unless parental objection See Asthma Nurse for education Asthma diary and action plan Refer to general paediatric clinic or respiratory clinic for follow-up as appropriate Book relevant lung function tests 94 Section 2. Respiratory system Chapter 30 – Ambulatory care of asthma E Chan, DK Ng Children with asthma usually presented with recurrent cough, wheezing, chest tightness or shortness of breath. Asthma is a chronic airway inflammation and the airway is hyper-responsive, causing reversible airway obstruction when airway is exposed to various risk factors. The patient is usually atopic with other co-morbid allergic diseases, positive skin prick test to aeroallergen and/or elevated IgE. Local prevalence: 13-14 years old: 10.2% in 2002 Initial assessment: classify severity of asthma Table 1. Severity of Asthma (to be filled in during the first visit) – start prophylaxis if ≥ step 2 Severity of Asthma Daytime Symptoms** - Wheeze, Nighttime Lung Function coughing bout, SOB Symptoms STEP 5 Continual symptoms Frequent FEV1 or PEF ≤ 60% Severe Limited physical activity predicted Frequent exacerbations Persistent PEF variability > 30% > 1 time a week FEV1or PEF > 60% STEP 4 Daily symptoms Moderate Daily use of inhaled short-acting to < 80% predicted β2-agonist PEF variability > Persistent Exacerbations affect activity 30% Exacerbations ≥ 2 times a week; may last days STEP 3 Symptoms > 2 times a week but > 2 times a month FEV1or PEF ≥ 80% Mild Persistent < 1 time a day predicted Exacerbations may affect activity PEF variability 20-30% STEP 2 Symptoms ≥ 1 time a month but ≥ 1 time a month FEV1or PEF ≥ 80% Frequent predicted ≤ 2 times a week Episode PEF variability < Asymptomatic and normal PEF 20% between exacerbations Exacerbations brief (from a few hours to a few days); intensity may vary STEP 1 Symptoms < 1 time a month < 1 time a month FEV1 or PEF ≥ 80% Infrequent Asymptomatic and normal PEF predicted Episode between exacerbations PEF variability < Exacerbations brief (from a few 20% hours to a few days); intensity may vary Asymptomatic No troubling cough No sleep Ditto No SOB disturbance No wheeze Normal exercise tolerance 95 Section 2. Respiratory system Assess level of control during follow-up (Table 2) Check patient’s medications and compliance Review exposure to risk factor. ie, passive smoking, smoking, house dust mites: any regular cleaning of beddings with water > 55°C, any curtain, carpet, incense burning Look for any co-existing allergic conditions like allergic rhinitis or infections like sinusitis. For any exacerbation, take note of duration and amount of bronchodilator used For those with isolated genuine exercise induced asthma, start prophylaxis if EIA symptom >=1 per week Table 2. Level of control Characteristic Daytime symptoms Nocturnal symptoms/ awakening Need for reliever/ rescue medication Limitations of activities Lung function (PEF or FEV1) Controlled (all of the following) Partly Controlled (any measure present in any week) None (≤ 2/week) > 2/week None Any > 3 features of partly controlled asthma present in any week None (≤ 2/week) > 2/week None Any Normal < 80% predicted or personal best (if known) None One or more / year One in any week Consider step down after 3-6 months Consider step up after 3-6 months Step up Exacerbations Rx direction Uncontrolled Table 3. Treatment Steps Start with ICS or LTA uncontrolled ICS + LABA or ICS + LTA uncontrolled ↑ICS + LTA + LABA controlled Grand Round 96 Section 2. Respiratory system Severe asthma for patients >= 6-year (for resp grand round) Definition “Asthma” requiring treatment according GINA steps 4-5 for previous year, i.e. high dose inhaled steroids + LABA +/- LTRA/theophylline OR. “Asthma” requiring oral steroids for >50% of previous year. Above medications needed to maintain control or uncontrolled asthma despite all of the above. May consider trial of systemic steroid for a period to demonstrate the bronchoconstriction is revesible as below Systemic steroid trial: Prednisolone, 0.5-2 mg /kg /day (40mg max) for 2 weeks If FEV-1 not increase by 15%, double for 2 more weeks (80 mg max) If effective, taper to the minimum level of systemic steroid required Triamcinolone 20-60 mg imi every 4 weeks at gluteal region Step up if partially controlled or uncontrolled despite good compliance and technique with medications and environmental control. (Beware of contribution from co-morbid conditions like allergic rhinitis, rhinosinusitis and alternative diagnoses, like foreign body, bronchiectasis). Step down if controlled > 3-6 months (may take into account of other factors) You may consider various lung function tests, i.e. spiromety / airway resistance studies with / without challenge / bronchodilator and FeNO assessment to give an objective assessment of the degree of control in lung function and airway inflammation. Difficult-to-treat asthma: ~5% of asthma cases Definition: symptoms interfering with daily living despite long-term treatment with inhaled corticosteroids in high doses Causes of difficult-to-treat asthma: Common: Adherence issues, Psychosocial issue, Environment (indoor and outdoor allergens and irritants, eg, tobacco smoke, NO2), cultural practices Wrong Dx of asthma, DDx: Hyperventilation, Vocal cord dysfunction, Gastroesophageal/supraesophageal reflux disease, Restrictive lung disease, Sleep apnea, Bronchiectasis, Endobronchial lesions, PCD, congestive heart failure Co-morbid condition that worsen asthma: Gastroesophageal/supraesophageal reflux disease, Allergic rhinitis, Chronic rhinosinusitis, Hyperventilation, Endocrinopathies (eg, hyperthyroidism, carcinoid syndrome), Allergic bronchopulmonary aspergillosis, Aspirin-exacerbated respiratory disease, Churg-Strauss syndrome/other vasculitis Genuine impaired effect of medication (rare) Beta 2 agonist: genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at amino acid residue 16 of the β2-adrenergic receptor 97 Section 2. Respiratory system Inhaled corticosteroid: smoking and/or passive smoking may impair the effect of inhaled corticosteroid; Glucocorticoid receptor anomalies: (1) genetically determined CS insensitivity through mutations in the glucocorticoid receptor (GCR) gene, (2) altered expression of GCR splice forms associated with CS insensitivity, (3) post-translational modifications of the GCR (4) conditions with decreased GCR binding affinity, (5) changes in regulation of CS-responsive genes, (6) altered CS metabolism LTRA: Lima and co-workers showed that a series of DNA sequence variants in the promoter regions of the arachidonate 5-lipoxygenase (ALOX5) gene were associated with a decreased response to montelukast and an increased risk of exacerbations Low, medium and high daily doses of inhaled corticosteroids (mcg) (GINA, April 2005) Adults and adolescents Inhaled corticosteroid Low Medium High Beclometasone dipropionate (CFC) Beclometasone dipropionate (HFA) Budesonide (DPI) Budesonide (nebules) Ciclesonide (HFA) Fluticasone propionate (DPI) Fluticasone propionate (HFA) Mometasone furoate 200-500 100-200 200-400 >500-1000 >200-400 >400-800 >1000 >400 >800 80-160 100-250 100-250 110-220 >160-320 >250-500 >250-500 >220-440 Triamcinolone acetonide 400-1000 >1000-2000 98 Children 6-11 years Low Medium High >320 >500 >500 >440 100-200 50-100 100-200 250-500 80 100-200 100-200 110 >200-400 >100-200 >200-400 >500-1000 >80-160 >200-400 >200-500 ≥220-<400 >400 >200 >400 >1000 >160 >400 >500 ≥440 >2000 400-800 >800-1200 >1200 Section 2. Respiratory system Chapter 31 - Acute bronchiolitis E Chan, D Ng Bronchiolitis: usually in children <3yrs old, caused by diffuse airway obstruction in the small bronchi and bronchioles Aetiology: RSV, Parainfluenza, influenza, adenovirus, rhinovirus Co-infection: Chlamydia trachomatis or Mycoplasma pneumoniae History: Cough, difficult breathing Feeding: Poor feeding, choking or vomiting Sleeping: irritability / unable to sleep through the night Cyanosis in young infant Examination: Hydration status, Respiratory rate, Signs for respiratory distress (insucking / use of accessory muscles), bilateral expiratory wheeze +/- creps, Modified CAS score, SaO2; Apnoea in young infant (consult PICU) Modified CAS Score: Score points SpO2 Wheezing Accessory Muscle Use Inspiratory BS’s CNS 0 95+ in RA None/end expiratory None Normal Normal 1 <95 in RA Entire expiratory phase Unequal Altered mental status/ agitated 2 <95 with FiO2 30% Expiration & inspiration Decreased Depresse Substernal, subcostal, intercostal, nasal flaring Supraclavicular, paradoxical respiration 1-2: Mild, 3-5: Moderate, >5: Severe Risk Factors: Boys, Low birth weight, Low socio-economic class, Crowded living condition, Parental smoking, Absence of breast-feeding (IgA in colostrum is protective) Investigation: CXR – hyperinflation (CXR not routinely indicated in afebrile child) NPA for viral IF Watch out for SIADH 99 Section 2. Respiratory system Asthma Predictive Index (for children < 3 years old) Major criteria Minor criteria Parental history of MD diagnosed asthma Allergic rhinitis Wheezing without infections Eosinophilia ≥ 4% Loose criteria: any wheeze in first 3years of life + one major or 2 minor criteria Stringent criteria: ≥ 3 wheezes in first 3 years of life + one major or 2 minor criteria Prediction of asthma at 6-13 years old: Loose – sensitivity 42%, specificity 84%, PPV 59%, NPV 73% Stringent – sensitivity 15.7%, specificity 97%, PPV 76%, NPV 68% Other predicting factors: allergy to house dust mite: OR = 3.23 documented airway hyper-responsiveness: OR = 4.94 Management: Treatment of acute attack Oxygen supplement up to FiO2 40% to maintain awake SpO2≥95% Consider high flow humidified nasal cannula oxygen started at max 8 L/min with FiO2 max 40% in moderate cases and take capillary gases (if >=normocapnea, consult PICU), Tube feeding or IV fluid if poor feeding affects hydration Bronchodilators (experience based, need to check individual response) – see Flow Chart Consider systemic steroid or high dose inhaled corticosteroids (e.g. fluticasone propionate 1,000 mcg/day) in those with severe attack Treatment If wheeze present ↓ Trial of ipratropium bromide (atrovent) 4 puffs through aerochamber ↓ Reassess 1/2 hour later ↙ ↘ Not useful Useful, Then Q6H prn + check wheeze Q6H Trial of salbutamol (ventolin) 4 puffs through aerochamber ↓ Reassess 20mins later ↙ ↘ Not useful Useful, then Q4H prn + check wheeze Q4H ↓ ↗ Trial of 3% hypertonic saline Neb 4ml (consider to use with bronchodilator)* ↓ Trial of 1 : 1,000 Adrenaline (nebulized)* (0.5 ml/kg, max 3 ml) – mixed up to total 4ml with NS ↓ If not useful, ↘ useful, Q4H prn for wheeze Significant respiratory distress (e.g. score >5) or requiring frequent inhaled medication (ie, Q1H) ↓ To PICU for NIV 100 Section 2. Respiratory system *If pt has partial response to 3% saline & adrenaline, consider 1.5mg 1:1000 adrenaline + 2.5ml 3% saline Neb Management options in recurrent cases, i.e., PRN 1-2wks montelukast; ICS (fluticasone 100mcg BD or equivalent) Preventions of RSV infection: Consider Palivizumab in infant with other risk factors (prematurity, chronic lung diseases, heart diseases)(consult resp team) 101 Section 2. Respiratory system Chapter 32 – Sleep-disordered breathing (SDB) DK Ng, E Chan Definitions: 1) Primary snoring - Snoring without any abnormalities, i.e. apnoea, hypoventilation, hypoxaemia, hypercarbia, sleep disturbance and daytime symptoms 2) UARS - AHI < 1 with daytime symptoms and paradoxical breathing 3) OSAS - AHI > ULN 4) Obstructive hypoventilation - PaCO2 > 50 mmHg > 25% of TST Normal Values Parameters Reference values Comment ≦1 AASM ≦0.4 Traeger N, only study using AASM criteria Time with SpO2 <90% (%TST) 0 Montgomery Desaturation (>4%) index (N/h) <1.6 Montgomery, Marcus SpO2 nadir (%) ≧92 Marcus, Uliel Periodic limb movement index (N/h) ≦4.3 Traeger, Montgomery Modified ESS (<12-year-old) Normal <=8 Marcus, Chan PDSS (>=12-year-old) Normal <=17 Yang CM WASO Refer to overleaf chart Maurice M. Ohayon, Mary Carskadon, Christian Guilleminault, Michael V. Vitiello PaCO2 >50mmHg <25% of TST AASM Apnea-hypopnea index (N/h) Central apnea index (N/h) 102 Section 2. Respiratory system Wake After Sleep Onset (Ref : Maurice M et al, Sleep 2004;27(7):1255-73) Investigations: - All children should be screened for habitual snoring - Polysomnography (PSG) should be performed if the attending clinician has a high suspicion of SDB - Give Melatonin 0.25-0.5 mg per kg (to be rounded up to whole number, max 3 mg) a) for all Down syndrome patients b) for patients who have difficulty in falling asleep Sleep endoscopy should be used to identify the main site(s) of obstruction. The most likely sites would be tonsils and/or adenoids. Multiple sleep latency test (MSLT) is helpful in children with suspected UARS Treatment: - Avoid sleep deprivation and medications with sedating effect - Surgery: e.g. tonsillectomy and adenoidectomy, uvulopalatopharyngoplasty (UPPPP), laser or radio-frequency ablation of redundant tissue, maxillo-mandibular advancement and tracheostomy - Continuous positive airway pressure (CPAP) - Weight reduction - Orthrodostic devices like rapid maxillary expansion, mandibular advancement device. - Myofunctional treatment maybe helpful 103 Section 2. Respiratory system Medical Rx of childhood OSA Goldbart AD et al. Pediatrics 2012;130:e575; Goldbart AD et al. Am J Respir Crit Care Med. 2005;172:364–370; Kheirandish-Gozal L et al. Pediatrics. 2008;122; Alexopoulos EI et al. Pediatr Pulmonol. 2004;38:161–167; Brouillette RT et al. J Pediatr. 2001;138:838–844; Kheirandish-Gozal L et al, Chest. 2014 Feb 6. ; Kheirandish L et al. Pediatrics. 2006;117:e61-e66 Follow-up: - Male gender and T&A undertaken before the age of 5 years have been found to be risk factors for OSAS recurrence after T&A. - Regular follow-up is important for children and adolescents with SDB. Post-operative PSG should be arranged, 3-6months, after surgery 104 Section 2. Respiratory system Table I. Approach to habitual snoring Habitual snoring (>3 nights / week) assess severity clinically (in resp clinic or sleep clinic) very severe No Hospital admission For overnight oximetry Yes Normal refer to have overnight PSG AHI > 1 No ABNORMAL Yes Primary snorer or UARS sleep endoscopy Daytime symptoms/ Abnormal ABP readings ADHD sypmptoms Yes No UARS Treat obesity, allergic rhinitis refer for myofunctional therapy Normal MSLT Repeat PSG 1 year later with MSLT the next day 105 ABNORMAL Section 2. Respiratory system Chapter 33 - Parapneumonic effusion and empyema E Chan, DK Ng Grading U/S grading 1. Anechoic 2. Ecogenic 3. septa 4. homogeneous echogenic 106 Section 2. Respiratory system Light’s classification and treatment scheme for parapneumonic effusions and empyema *Intrapleural fibrinolytic (Urokinase) Dose: 56,000units per m2 BSA (round up to nearest 1,000units, maximum 100,000units), dwell time 4hrs, Q12H, for 3 days (concentration 10,000units in 10ml NS); individualized extended use (up to 6 days) may be considered for cases with persistent drainage. Failure: limited drainage but persistent pleural effusion, persistent fever and respiratory symptoms after 3days of intrapleural urokinase. **watch out for high output within a short period of time, clamp drain if output >10-15ml/kg within 4 hrs to avoid pulmonary re-expansion edema and hypovolemic shock. 107 Section 2. Respiratory system Blood tests + CXR Start antibiotics + Chest Sonography Pleural effusion > 1cm No Yes Chest drain** + Pleural fluid x pH, WBC, Gram stain, C/ST, LDH, protein, glucose (AFB Smear, C/ST, TB PCR, ADA as indicated) (cytology, pleural Bx as indicated (serosanguinous fluid)) Cont. Antibiotic + monitoring Remember to get urgent pH with capillary tube for analysis by blood gases machine, WBC, Gram stain Gram stain +ve or pH < 7.2 or glucose < 2.2 or LDH >1000 µ/L, or WBC >10,000/mm3 or protein > 5gram/dL or USG showed fibrin/septa + ve Intrapleural Fibrinolytic* - ve Cont. Antibiotic + Chest drain Pleural effusion<1cm + drain output <20ml/day consider early referral if frank pus/poor response Success Failed No VATS Yes Clamp drain; off drain if no re-accumulation Follow by 1-4 wks PO antibiotic guided by CRP, fever, O2 dependency 108 Section 2. Respiratory system Chapter 34 - Pulmonary function tests in children E Chan, J Wong, DK Ng Test You are looking for Spirometry Spirometry with bronchodilator (include FeNO) Exhaled NO Basic parameters: Flow volume loop, FEV1, FVC, FE50 Asthma, may need repeated testing to demonstrate bronchodilator response Eosinophilic airway disease IOS with bronchodilator Bronchodilator response, can be performed by ≥ 3yrs old Exercise challenge test MIP/MEP Exercise induced bronchoconstriction Airway hyper-responsiveness Assess severity of asthma Respiratory muscle weakness Erect and spine VC Respiratory muscle weakness Total lung volume TLC, lung volume DLCO Diffusing capacity, TLC, FRC VO2 Max The fitness of child, the limiting factor of exercise A test for fitness in patients with chronic cardio-respiratory disease Methacholine/mannitol challenge test 6 minutes walk In general, a cooperative child (usually ≥ 6 yrs old) with coordinated expiratory and inspiratory effort is required to perform spirometry. Spirometry can be booked in those < 6 years after special consideration. Otherwise, IOS is an alternative. Children who can perform spirometry and run on a treadmill can perform VO2 max (~ at least 6 years old). Measuring DLCO and lung volume required patience and good breath holding technique, i.e. at least 9-year-old) Relative contraindications for spirometry: active respiratory infections, low FEV1 (see low FEV1 protocol), history of recurrent pneumothorax, aortic aneurysm, any unstable respiratory or cardiac conditions, such as uncontrolled hypertension, heart attack or stroke in recent 3 months. Please obtain written consent for the test. 1. Basic lung function Baseline spirometry (FEV1, FVC, flow volume loop), refer chart for lower limit of normal Obstructive Restrictive FEV1 ↓↓ → FVC ↓ or → ↓↓ FEV1/FVC ↓ ↑ FRC ↑ ↓ RV ↑ ↓ TLC ↑ or → ↓ RV/TLC ↑ → or ↓ 109 Section 2. Respiratory system Spirogram from Merck Manual A. Normal B. Obstructive C. Restrictive D. Fixed upper airway obstruction E. Variable extrathoracic obstruction F. Variable intrathoracic obstruction 2. Airway bronchodilator response and response to challenge, usually used to investigate asthma, chronic cough and chronic lung diseases Bronchodilator test (spirometry with pre and post bronchodilator) + FeNO It is a simple test. It is good for monitoring and use as an initial screening test. However, we may need to repeat the tests over a period of time to document a positive bronchodilator response in asthma. Positive test: FEV1 increase ≥ 12% 110 Section 2. Respiratory system Impulse Oscillometry System (IOS) -A tidal breathing test -It is a measure of airway resistance by oscillation technique and it is a reasonable alternative in young children. A single measurement is of limited value. It is used to look for bronchodilator response. R(5) decreases by >=29% is defined as significant bronchodilator response. -Test quality is influenced by pt’s breathing pattern. Apart from visual confirmation by Tech. Coherence of R(5) and R(20) should be >=0.7 and >=0.9 respectively. -R(5)= Central + Peripheral Resistance -R(20)= Central Resistance R(5) – R(20) = peripheral Resistance IOS Curve pattern 1) Normal Lung Function 4) Extra Thoracic Airway Obstruction Resistance R R5, R20 normal R R(f) no frequency dependence R5 R20 Normal reference 5 20 5 HZ 2) Peripheral obstruction R5, Increased, > ULN R R20 is normal R(f) frequency Dependence present Normal 5 20 HZ 3) Central obstruction R R R5, Increased, >ULN R20 increased, >ULN R(f) no frequency dependence Normal 5 20 HZ 111 Normal f [Hz] 20 HZ Section 2. Respiratory system Challenge test (Methacholine, mannitol and exercise) Exercise test is important to assess exercise induced bronchospasm To rule out asthma, use methacholine challenge test. To rule in asthma, use mannitol challenge test Medication challenge test has a better negative predictive value, may help assess the risk of developing asthma, assess severity of asthma & assess response to treatment. In general, mannitol test has a better J-index (i.e. sensitively + specificity) than methacholine challenge test (Patient need to inhaled dry powder for mannitol test, ie, >60L/min inspiratory flow required) For patient who cannot tolerate a large drop in FEV1, step wise tests (medication challenge) is more suitable. If the patient cannot tolerate any drop in FEV1, challenge test should not be booked. 1) Exercise test: EIB: mild, moderate, or severe if the percent fall in FEV1 from the pre-exercise level is >10%-25%, >25%-50%, and >50%, respectively 2) Methacholline challenge PC20 = provocative concentration causing a 20% decrease in FEV1 PC20 (mg/ml) Interpretation > 16 Normal bronchial responsiveness 4.0-16 Borderline BHR 1.0-4.0 Mild BHR (positive test) < 1.0 Moderate to severe BHR Extrathoracic airway hyper-responsiveness (EAHR) with methacholine challenge: PD25FIF50; cutoff concentration <8mg/ml = +ve, EAHR is found in those with upper airway cough syndrome usually due to allergic rhinitis. 3) Mannitol Challenge test: PD15= provocative dose causing a 15% drop in FEV1 FeNO = exhaled nitric oxide A non-invasive measure of airway inflammation ATS: <25ppb(<20ppb in children) indicate non-eosinophilicor no airway inflammation; high FeNO >50ppb(>35ppb in children) or rising FeNO (>40% change from previous stable levels) implies uncontrolled or deteriorating eosinophilic airway inflammation. 112 Section 2. Respiratory system Lung volume: Book DLCO and TGV(Pleth) +/- nitrogen washout DLCO (Hb corrected) normal values: less than the lower limit of normal (LLN) but greater than 60% of predicted is mild, between 40 and 60% of predicted is moderate, and less than 40% is severe. Low DLCO: restrictive lung disease, isolated low DLCO with normal lung volume: anaemia, pulmonary vascular disease High DLCO: in pulmonary haemorrhage, polycythaemia, increase pulmonary blood flow, such as asthma, pregnancy and obesity RV/TLC normal: <0.35 Exercise tolerance/cardiopulmonary fitness 1) 6 minutes walk: refer to chart for normal values VO2 Max/Peak (a cardiopulmonary challenge test) 2) CPET (cardiopulmonary exercise test) 113 Section 2. Respiratory system Peak VO2 Normal Anxiety Obesity Low <80% Mild disease Anaerobic threshold Abnormal (AT <0.4 of predicted VO2 max) Normal Breathing reserve Breathing reserve Low <0.2 Normal Poor effort Deconditioning Ventilatory impairment Coronary disease Normal Low <0.2 Cardiac impairment O2 pulse Cardiopulmonary lesion ↓ Exercise induced arterial hypoxemia may occur in trained athletes: mild(93-95% SaO2) moderate(88-93% SaO2), severe (<88% SaO2) Respiratory muscle weakness Book spirometry, DLCO, MIP, MEP, erect and supine VC Normal values: MIP [boys: (2.58 + age x 0.39) x 10 cmH2O; girls: (2.43 + age x 0.28) x 10 cmH2O] MEP [boys: (35 + 5.5 x age) cmH2O; girls: (24 + 4.8 x age) cmH2O] MIP helps to differentiate whether restrictive lung disease is due to respiratory muscle weakness or chest wall limitation MEP is usually > MIP, if MEP is < MIP, there may be a prevailing expiratory muscle weakness, i.e. SMA MEP > 45 cmH2O is necessary for effective cough. Checking peak cough flow is an alternative to monitor a patient’s coughing ability. Fall in VC when the patient changes from seated to supine position < 10% : normal, 10-20% : suspicious of diaphragmatic paralysis > 20% : significant diaphragmatic paralysis Infant Lung function test Restrictive if FVC less than LLN Obstructive if MEF 75/25 and / or FEV 0.5 or Rrs <LLN 114 Section 2. Respiratory system Chapter 35 - Bronchoscopy E Chan, D Ng Indications: Stridor / noisy breathing Persistent / recurrent wheezing Recurrent / persistent consolidations Atypical and unknown infiltrates Localized hyperinflation Chronic cough Suspected foreign body aspiration Haemoptysis Evaluation of the artificial airway Look for the underlying causes in CPAP/oxygen dependency in neonates Pre-bronchoscopy preparation For children with history of asthma or wheeze, please give bronchodilator, e.g. salbutamol 8 puffs through aerochamber, on call to endoscopy suite. Therapeutic bronchoscopy: Restoration of airway patency Mucus plugs or blood clots Alveolar filling disorders (alveolar proteinosis, lipid pneumonia) Special procedures: Bronchoalveolar lavage Brushing or biopsy of bronchial mucosa Biopsy of endobronchial lesions Administration of drugs like DNAase Endoscopic intubation Contraindications: Absolute Procedure will not yield any further useful clinical information Diagnosis of acute epiglottitis Relative Pulmonary hypertension Baseline hypoxia Uncorrected bleeding diathesis Duties of bronchoscopist : Fill in time out form Perform procedure with clear objective in mind Start the procedure upon clear signal from the sedation medical staff after checking the sedation staff has been appropriately trained. Maintain clear communication with sedation staff and endoscopy nurse. 115 Section 2. Respiratory system Chapter 36 - Preparation for endoscopy E Chan, DK Ng 1. On admission for endoscopy, please check the endoscopy list to confirm booking. If not, send another booking form. 2. Check for signed consent form. 3. Clear fluid (GES / water / fruit juice without pulp) allowed for up to 2 hours before endoscopy. 4. Breast milk can be taken 4 hours prior to endoscopy 5. No solid food (including milk / jelly) for 6 hours prior to endoscopy 6. Inform the parents to deprive sleep by 3 hours the night before the procedure 7. For sleep endoscopy, give Melatonin 0.25-0.5 mg per kg (to be rounded up to whole number place, max 3 mg) 45 minutes before the scheduled procedure 8. Keep the child on the stretcher in a quiet and darkened room to facilitate sleep and be accompanied by parents 9. Heparin block with short extension set before endoscopy (size of at least gauge 22 if patients > 6 years old and >=20G for patient >10yrs old) 10. Case doctor completed the sedation form before endoscopy, prescribe prophylactic antibiotic as per protocol. 11. M.O. assigned for sedation complete the time in form and he/she is responsible for administering sedatives, maintain ventilation (ie, may need CPAP, BiPAP or nasopharyngeal airway and T-piece resuscitator) and resuscitation during and after the procedure 12. Please discuss with endoscopist about desired level of sedation and potential complications of the case 116 Section 2. Respiratory system Chapter 37 - Positive Mantoux test E Chan, DK Ng 1. Risk of TB among Primary Schoolchildren with MT2 ≥ 20mm in 5-year FU - 1% of primary school children had this reaction - Relative risk of PTB Male : 49 Female : 33 2. Relationship of size of MT2 and development of PTB in 5-year FU Size of MT2 (mm) % of development of PTB 0-4 2 5-9 2 10-14 3 15-19 15 ≥ 20 34 3. Risk of TB with different MT2 responses in 4-year FU Size of MT2 (mm) odds ratio 10 4 20 16 4. Risk of TB among young household contacts in 6-year FU Out of 50 patients with MT2 ≥ 10mm, 4 (8%) developed PTB in 5-year FU Flow chart for positive Mantoux test (consult resp team) +MT2 (≥ 10mm induration) Refer resp team Pul. TB NPA after cough / EMGL x AFB smear, C/ST x (3) PCR x (1) CXR + ESR +ve -ve Symptoms, clinical risk (ie, close TB contact) -ve +ve Contrast CT thorax (preferably with 320 CT Interferon Gamma scanner to decrease radiation by 50%) +ve -ve +ve Pul. TB LIBI -ve Bronchoscopy + BAL Normal +ve Pul. TB -ve LTBI Latent TB infection (LTBI) : Isoniazid 10-15 mg/kg/day for 9 months would decrease the chance (life time risk around 10% and higher in those < 3 years) of TB disease by up to 90% in the absence of new contact with open PTB. 117 Section 2. Respiratory system Chapter 38 - Pulmonary tuberculosis DK Ng Clinical features: 1) persistent cough for > 2 weeks 2) objective weight loss in the preceding 3 months 3) fatigue Presence of all 3 symptoms is suggestive of PTB (80% sensitivity, 90% specificity) in HIV -ve children ≥ 3 years Radiological imaging: Hilar lymphadenopathy is the most common feature in CXR Normal CXR in 20% of PTB CXR may be repeated after one month of treatment and at the end (60% have persistent albeit improved CXR). Contrast CT scan of thorax is very sensitive but not routine Bacteriology: Sputum: 3 specimens (one early morning) Early morning gastric lavage (EMGL): 3 specimens for TB culture or Xpert test Nasopharyngeal aspirate after cough: any time of the day for TB culture or Xpert test AFB smear positive only in 10-15% Culture positive in < 40% Treatment: Isoniazid 10-15 mg/kg/day (max 300 mg) for 6 months Rifampicin 10-20 mg/kg/day (max 600 mg) for 6 months Pyrazinamide 20-40 mg/kg/day (max 2-3 gram) for 2 months Ethambutol 15-25 mg/kg/day (max 2-5 gram) for 2 months Referral to DH Chest clinic may be made for DOTS All cases should be referred to respiratory clinic for follow-up Pyridoxine supplement to avoid peripheral neuropathy of isoniazid is indicated for HIV positive children, malnourished, breastfed or premature infants Corticosteroids (prednisolone 2 mg/kg for 4-6 weeks then taper off in 2-4 weeks) is indicated for endobronchial TB or profuse pleural effusion or TB meningitis Isolation policy: Children with suspected or confirmed TB should be isolated if • presence of cough • cavitation on CXR • sputum or EMGL is AFB smear positive • respiratory tract disease with involvement of the lung / airways, including larynx • extensive pulmonary infection • suspected congenital TB Children with little cough and negative sputum / EMGL x AFB can be hospitalised in an open ward. 118 Section 2. Respiratory system Chapter 39 - Primary spontaneous pneumothorax in adolescents KL Kwok, DK Ng Definition of large pneumothorax (Any one) ● ≥ 3cm apex to cupola (ACCP) ● ≥ 2cm between lung margin and chest wall (BTS) ● Complete dehiscence of the lung from the chest wall (Belgian) ● % of pneumothorax = (DH3- DL3)/DH3 ≥ 50% (Light Index) – see appendix Management ● Any symptomatic (SOB or significant chest pain) pneumothorax regardless of size or large pneumothorax warrants treatment ● Persistent (> 4-7 days): surgical intervention ● Small: treat with HHHF of FiO2 just enough to keep SpO2 = 100% ● CXR 2 weeks after discharge, ● no air travel for 6 weeks, check FiO2. Simple aspiration ● Exclusion criterion: tension pneumothorax ● 16G catheter (ID of 1.7 mm that allows guidewire of 0.87 mm to pass through: see picture) and 50 cc syringe and three-way tap and underwater exit tube, aspirate air up to 4 L or resistance ● CXR immediately after procedure to confirm success and 4 hours later to look for reaccumulation ● Failure i.e. still have free drainage after 4L has been aspirated should lead to in-dwelling catheter insertion ● Success rate: 50-72% ● Recurrence at 1 year: 20% ● Mean time of recurrence: 3 months ● Advantage: less painful, cheaper, shorter hospital stay ● Problem: frequent kink, time consuming, difficult to keep sealed catheter in place for chest X-ray Small bore in-dwelling catheter + Heimlich valve +/- suction ● 8F to 14F ● Success rate with Heimlich valve: 66% at 48 hours ● Success rate for the group that required follow-on -10 to -20 cm water: 71% ● Recurrence rate: 24% ● Mean time of recurrence: 3 months ● No diving after pneumothorax unless bilateral surgical pleurectomy done Surgical intervention ● Indications: second ipsilateral, first contralateral, first bilateral, persistent, spontaneous haemothorax, high risk occupations e.g. pilots ● VATS ● Bleb removal ● Talc or minocycline pleurodesis 119 Section 2. Respiratory system Summary of success rates for management strategies for primary spontaneous pneumothorax Strategy Conservative Aspiration ICC Small bore / pigtail catheter Success Rate (%) 79-90 50-83 66-97 74-100 Curr Opin Pulm Med 2009;15:376-379 Appendix: Formula for Calculating Pneumothorax Light Index (The only formula used in our unit) DH3 - DL3 DH3 At hilar level Picture: 120 = % of pneumothrax Section 2. Respiratory system Primary Spontaneous Pneumothorax Symptomatic (regardless of size) or Large pneumothorax Small pneumothorax Conservative management with high flow heated humdified oxygen nasal cannula (FiO2 ~ 40%) Try simple aspiration in first attempt Aspiration > 4L Insert guidewire through the angiocath + with help of dilator, insert chest tube (pigtail) *see picture Aspiration till resistance CXR to confirm lung expansion Symptomatic or large pneumothroax Connect to Heimlich valve or underwater seal Small pneumothorax Insert chest tube (pigtail preferable) CXR to confirm position of chest tube CXR 24 hours after insertion (see next page) Next page 121 Section 2. Respiratory system CXR 24 hrs after insertion Failure Suction (-20 cmH2O) and watch out for S/S of pulmonary edema Daily CXR Persistent airleak > 4 days Lung Expanded For VATS or chemical pleurodesis off suction for 1 day Persistent airleak > 4 days clamp drain *monitor closely for reaccumulation of pneumothorax S/S of pneumothorax Immediate CXR CXR 24 hours later Persistent airleak Unclamp chest drain Lung expanded Remove chest tube Persistent airleak > 4 days 122 Section 2. Respiratory system Chapter 40 – Modified bronchoalveolar lavage E Chan, DK Ng 1. Prepare appropriate size suction catheter, equipments and body temperature normal saline: Each aliquot: 1 ml/kg for < 5kg, 10 ml for 5-40 kg, 20ml for > 40kg 2. Gently advance the end-hole catheter till resistance. Attach the syringe with warm saline to catheter. Inject saline into the catheter whilst occluding the side opening of ET Tube adaptor. Allow a few breaths. Aspirate BAL by syringe. 3. Repeat step 2 for another aliquot (aliquot and volume required depends on tests ordered) 20ml Syringe Suction catheter Connect to T-piece or Ventilator or Neo puff To Suction Disinfected L – Shape adaptor Mucus Extractor Advanced down the airway until resistance Quantitation of Lipid-Laden Alveolar Macrophages (Pediatr Pulmonol 1999;28:83-88) 900 alveolar macrophages were evaluated microscopically for lipid phagocytosis (level of magnification: 40 x 10). Each macrophage was graded according to the amount of lipid in the cytoplasm, with a score of 0-4 (0, 1, 2, 3, 4 = 0, 1/4, 1/2, 3/4, totally filled respectively). The total score (0-3600) was determined by taking the summed total grades of 900 cells. LLAM score > 200 is highly suggestive of aspiration pneumonia If total number of macrophage counted is less than 900 and the total score of the counted macrophage criteria is less than 200, check the number of macrophage counted. If less than 500, use Furiza criteria by pro rata division to 100. (Furuya et al 2007: LLMI >165, sen 98.6% spec 78% for patients with aspiration.) If more than 500, use Colombo by pro rata multiplication to 900. 123 Section 2. Respiratory system Chapter 41 - Skin Prick Test E Chan, A Yip Indications: - Confirm sensitivity (relevance of such sensitivity to allergens should be carefully interpreted in the light of clinical suspicion) - To confirm atopy - To confirm food allergy (type I allergy) - To predict outcome of open food challenge Results in KWH: Top 5 allergens = House dust mite*, dog, cat, cockroach and grass pollen Chance of major systemic reaction: 0.033% in literature and “NIL” in KWH case series (n= 1,365) Procedure: 1. Explain the procedure to parents and child and child must be physically well 2. Ensure anti-histamines, cough medications or TCM has not been taken for at least 1 week 3. Ensure topical steroid has not been applied to the tested area for at least 1 week 4. Sit the child comfortably; request nursing staff’s assistance if envisaging child will be struggling 5. The volar surface of the forearm is usually chosen but ensure that there is no active eczema. The back is an alternative site. 6. Ensure that the skin is clean, and if in doubt wash the site 7. Use a marking pen to divide the skin into areas 8. Place positive & negative control onto skin. Specific food allergen should be tested for food allergy. Whole panel of aeroallegen should be tested for asthma/ atopy/ recurrent bronchiolitis/ pre-school wheeze 9. A small drop of allergen solution is placed on the skin with at least 2-3 cm apart 10. Avoid placing allergen solution in areas 5 cm from the wrist and 3 cm from the antecubital fossa if possible (this may be difficult in infant) 11. A sterile lancet is passed through the solution at 45° to 60° angle to the skin with the bevel facing up, the skin is then gently lifted, creating a small break in the epidermis through which the suspected allergen solution penetrates without drawing blood, or Stallerpoint inserted at 90° 12. This step is then repeated for each allergen 13. The excess solution is removed with cotton wool making sure that there is no cross contamination 14. Wait for 15 minutes then examine for wheal (not erythema) 15. Cover the reaction site with a cellulose tape & outline the wheal with a marking pen 16. Transfer the cellulose tape to a piece of paper. Obtain wheal mean diameter (WMD), which is the average of the largest wheal diameter & length perpendicular to it 17. The child is observed for another 15-20 minutes & can be discharged Definition of positive SPT: - WMD Reported = WMD Allergen – WMD Negative Control - Positive if WMD Reported ≥ 3mm *House Dust Mite - B tropicalis is the most common & most important mite species in tropical countries & Hong Kong. - B tropicalis 5 is the major allergen with 92% of allergic patients sensitized to it. 124 Section 2. Respiratory system Chapter 42 - Primary ciliary dyskinesia and non-CF bronchiectasis E Chan, A Yip, DK Ng Features of PCD: Chronic oto-rhino-sinopulmonary (ear, nose, sinus and lung) disease +/situs inversus/heterotaxy Signs & symptoms: persistent rhinorrhea (76% PCD), serious otitis media (very common in young children), acute otitis media (common >50% in <5yrs old, uncommon afterwards), sinusitis, chronic wet cough (persistent bacterial bronchitis, bronchiectasis affecting >50% PCD children & 100% PCD adult, middle & lower lobe affect more), clubbing (increase with age, >80% in adult PCD), infertility (~50% in male, variable in female), ectopic pregnancy (female), hydrocephalus (rare), situs inversus (40-50% PCD), situs heterotaxy (6% PCD) , unexplained oxygen dependency in neonate (>75% PCD) Dx investigations: • Saccharin test (out of favor because of inaccuracy especially those <6yo) • Nasal FeNO: screening test (very low in PCD, may be normal in some cases) • Ciliary beat pattern & frequency study (depends on availability) • Electronic microscopy exam of nasal/bronchial cilia ultrastructure (current method of choice but false +ve happens with intercurrent infection) • Cell culture (eliminate environmental influence, free from secondary changes; depends on availability) • Genetic testing: Test may be considered for DNAI1 and DNAH5 (outer dynein arm proteins defects which account for <40% of PCD mutations) • Semen study in adult men Follow up investigation: • Sinopulmonary symptoms & exacerbation diary +/- peak flow/FEV1 diary • Pneumatic otoscopy / tympanogram at least 6 monthly, in cases with chronic SOM, use of ear drops (antibiotic + hydrocortisone) & hearing aid are preferable to grommet insertion (which may lead to unresolved ear discharge) • Sputum/induced sputum C/ST every 3-6 months • Lung function test with bronchodilator every 3-6 months • HRCT (to detect bronchiectasis, balance risk with radiation) • Psychosocial assessment as needed Early diagnosis & implementation of multi-disciplinary approach in an experienced center is associated with better outcome Nasal management: baseline: daily hypertonic saline nasal irrigation, BD-TDS nasal irrigation +/- antibiotics with increased symptoms, consider nasal corticosteroid in selected cases Ambulatory pulmonary management, watch out for aggravating/co-morbid factors Steps of management go up and down according to worsening or improving level of symptoms respectively. 125 Section 2. Respiratory system Severity classification Symptoms in the Controlled previous 4 weeks Partly controlled Cough Mild/baseline Significant Increased Sputum volume and color Limitation of physical activities Affect social life/daily activities Lung function (FVC or FEV1) Emergency admission Baseline volume/ Whitish sputum Signiciant Increased volume or Yellowish/greenish color None Any None Any Normal < 80% predicted or personal best None One or two / year Uncontrolled > 3 features Three or more / year Management Aims: to maintain lung function, decrease exacerbation & emergency admission, allow normal daily life Methods: Education about PCD, avoid pollutants exposure Aerobic exercise 45 minutes/day Flu immunization Adequate nutrition (caloric requirement 110-120% of RDA in symptomatic PCD) Acute pulmonary exacerbation management Patient with underlying lung disease may deteriorate quickly. Close monitoring, prompt and appropriate antibiotics, adequate respiratory support (ie, NIV) are usually required. Choice of antibiotic is usually based on latest sputum result. 126 Section 2. Respiratory system Steps in managing PCD, step up if not controlled despite good adherence with current step Step 1 Daily 5.85% hypertonic saline Neb Step 2 BD 5.85% hypertonic saline Neb Daily chest PT BD chest PT Daily Breathing exercise with resistor (Acapella) BD Breathing exercise with resistor (Acapella) *Bronchodilator prn *Bronchodilator prn #Antibiotic (2 weeks course) Step 3 TDS 5.85% hypertonic saline Neb TDS chest PT TDS Breathing exercise with resistor (Acapella) *LABA + ICS #”Eradication and/or ^long term cycled therapy with Neb and/or systemic antibiotic Consider other measures to help airway clearance (ie, CPAP, cough assist) *Only in those with documented airway bronchodilator responsiveness #Sputum/induced sputum should be performed at least every 3 months, prescribe antibiotic according to latest sensitivity result; start with amoxil if sputum showed commensals only/ amoxil + clavulanic acid if the patient is at risk of aspiration. Dosage according to BNF for severe infection #Most commonly encountered organisms: Haemophilus influenza, Staphylococcus aureus, Streptococcus pneumonia. Atypical Mycobacterium & Pseduomonas species tend to affect children of older age “Eradication therapy for pseudomonas: IV anti-pseudomonal antibiotics for 2 weeks +/Colistin neb 75-150mg (1-2 million units) BD for 2wks-3 months ^long term cycled therapy, usually start with 2-4wks of PO and/or Neb antibiotic, to be given every 3 months. Nebulized therapy: Gentamicin 80mg BD or colistin 1-2MU BD (depends on bacterial culture sensitivity) ^Three times per week azithromycin (10mg/kg/dose) or once a week of 30mg/kg/week may help to reduce exacerbation and cough 127 Section 2. Respiratory system Chapter 43 - Nasal lavage A Yip, DK Ng Indication: Rhinosinusitis, allergic rhinitis, rhinitis & common cold Action: - Flushes dirt, airborn allergens (dust, pollen etc), pollutants & bacterial-filled mucus - Remove thickened mucus, decrease inflammation, improve mucociliary clearance - Also loosen & thin the mucus, easier to expel Prescription: - 1.5% NaCl 5-10ml to each nostril LA daily to TDS (allergic rhinitis, sinusitis) - 1.5% NaCl 60ml to each nostril LA daily to TDS (PCD, step up treatment for allergic rhinitis & sinusitis), using a commercial squeeze bottle (below) - Commercial preparation Different content in different sachets preparation; as per instruction Ingredients in Commerically Available Sachet*: o NaCl + Baking Soda (NaHCO3): Sometimes used, buffering agent, alkaline pH 7.6 is better for ciliary function, higher mucus fluidity o Sodium Citrate/ Citric Acid: Optional, balance pH, improve sense of smell o Aloe Extract: Optional, prevent nasal dryness Nasal Devices*: - Syringe: Head tilt; cheap, repeated small volume lavage - Neti Pot: Head tilt; rely on gravity; repeated practice - Squeeze Bottle (different brands): Head upright; positive pressure to drive water into sinuses & nasal cavities for more complete rinsing; avoid high pressure that force fluid into middle ear, causing infection & earache; anti-backwash valve preferred - Electric Irrigator: Head upright; expensive; convenient; pulsatile water pumping action at a predetermined fixed pulse cyclic rate, claimed to simulate nasal cilia hairs, promote better sinus health & reduce severity of allergic reaction Methods: Method 1 (Head-tilt) 1. Tilt head to one side or lie on bed on the side 2. Breath through the mouth. Avoid nasal breathing, talking or swallowing for the risk of aspiration 3. Push in irrigation fluid via one nostril (via nostril on upper side) and the fluidwill exit from the other nostril or through the mouth. 4. Repeat Step 3 with head tilted to the other side 128 Method 2 (Upright) 1. Sit down with head up. 2. Hold the breathe. 3. Push in irrigation fluid via one nostril 4. Lean forward with head down and allow irrigation fluid to drip out from nostrils or split out from throat. Section 2. Respiratory system *Choices Available for Nasal Lavage/ Irrigation/ Douche 129 Section 2. Respiratory system Chapter 44 – Reflux Laryngitis E Chan Laryngopharyngeal reflux (LPR) is the retrograde movement of gastric contents into the larynx, pharynx, and upper aerodigestive tract Symptoms Dysphonia, globus sensation, cough, subglottic stenosis, muscle tension dysphonia, laryngospasm, vocal process granuloma, apnoea, asthma/wheeze, and possibly chronic sinusitis Reflux finding score (RFS): 8-item clinical severity scale; 0 (no abnormal findings) to a maximum of 26 (worst score possible) One adult study showed RFS greater than 7 as suggestive of LPR. • • • • • • • • Pseudosulcus (infraglottic edema) Ventricular obliteration Erythema/hyperemia Vocal cord edema Diffuse laryngeal edema Posterior commissure hypertrophy Granuloma/granulation Thick endolaryngeal mucus 0 absent, 2 present 0 absent, 2 partial, 4 complete 0 absent, 2 arytenoids only, 4 diffuse 0 absent, 1 mild, 2 moderate, 3 severe, 4 polypoid 0 absent, 1 mild, 2 moderate, 3 severe, 4 obstructing 0 absent, 1 mild, 2 moderate, 3 severe, 4 obstructing 0 absent, 2 present 0 absent, 2 present 130 Section 2. Respiratory system Chapter 45 - Useful value E Chan, DK Ng Ventilation Normal dead space in adult = 150 ml Minute ventilation - dead space ventilation = alveolar ventilation = 5-6 L/min (adult) Pleural pressure Normal value from -3 to -5cm water Keep suction pressure no more negative than -20 cmH2O during aspiration of pleural effusion to avoid trauma to the lung Pleural effusion: Posterior costophrenic angle obscured in lateral CXR = 50 ml Costophrenic angle obscured in PA CXR = 200ml Diaphragm contour obscured = 500ml Chylothorax: > 1.1 mmol/L triglyceride (with oral intake) and a total cell count > 1,000 cells/µL with a lymphocyte fraction > 80% Respiratory Indices Calculation PaO2/ FiO2 ratio: Remarks e.g. PaO2 = 8kPa, Fio2 = 60% ＜300 = mild ARDS ＜200 = moderate ARDS ＜100 = severe ARDS = 2 8 × 7.5 = = 100 2 0.6 i.e. severe ARDS Oxygen Index (OI): = ＞8.1 = ARDS ＞15－25 consider iNO in case of PPHN ＞40 ＝ ECMO MAP × FiO2 × 100 PaO2 × 7.5 Alveolar- arterial O2 Gradient: = 2(. − − = 716 × 2 − 2 − 2 0.8 ＜10 mmHg (normal) 2 × 7.5 − 2 × 7.5 0.8 (Hong Kong is at sea level) Ventilation Index (VI): See trend for↓or↑ventilation PaCO2(mmHg) × PIP × RR = 1,000 Compliance / kg: = Newborn 2－2.5ml/cmH2O/ Kg ＜0.6ml / cmH2O/ Kg → RDS ＜1ml/ cmH2O/ Kg → BPD Cdynamic BW 131 Section 3. Cardiovascular system Section 3: Cardiovascular system 132 Section 3. Cardiovascular system Chapter 46 - Ambulatory management of hypertension L Leung 1. Definition of hypertension Hypertension = BP ≥ 95th percentile on at least three separate occasions. Each occasion: at least 2, preferably 3 measurements taken at least 2 min apart, the average compared with age, gender and height (4th report mercury sphyg norms or 2008 HK oscillometric norms). 4th report recommends that oscillometric readings ≥ 90th percentile repeated by auscultation. Standards for systolic and diastolic BP for infants < 1 year old are according to the 2nd Task Force. 1.1 Stage 1 and 2 Hypertension “Stage 1” hypertension: recheck in 1-2 weeks; if persistently elevated on 2 more occasions, evaluate within a month or sooner if symptomatic. “Stage 2”: evaluate within 1 week, or immediately if patient is symptomatic. 1.2 Those with high casual BP should have 24hr ABP done to exclude WCH, elucidate BP pattern. (HK 2014 ABP norms) 2. Commonest causes of secondary hypertension (HT) in children 2.1 Causes of HT classified according to age (in decreasing order of frequency): Table 1 The younger the age, the higher the BP, the greater the chance of a secondary cause. Table 1 Commonest causes of secondary hypertension in children Newborn First year 1-6 years 6-12 years Renal vascular ♦ Renal artery thrombosis or stenosis ♦ Renal vein thrombosis Renal impairment Congenital renal abnormalities Coarctation of aorta Others: Drugs, BPD Coarctation of aorta Renal vascular disease Renal parenchymal disease* Iatrogenic Tumours Renal parenchymal disease* Renal vascular disease Coarctation of aorta Rarely: Endocrine diseases Essential HT 133 Obesity OSA Renal parenchymal disease* Renovascular disease Essential HT Coarctation of aorta Rarely: Endocrine diseases Iatrogenic 12-18 years Obesity OSA Essential HT Iatrogenic Renal parenchymal disease* Renovascular disease Rarely: Monogenic HT Endocrine diseases Coarctation of aorta Section 3. Cardiovascular system 3. Diagnostic Approach to child with persistent hypertension See Fig 1 Evaluation Algorithm 3.1 History Symptoms suggestive of secondary HT: eg. Urinary symptoms, joint pain, abdominal pain, oedema, muscle weakness or cramps, weight loss, palpitations, sweating, fevers, flushing attacks Symptoms suggestive of TOD: headache, epistaxis, vertigo, impaired vision, chest pain, dyspnoea Sleep history: habitual snoring, observed apnea, daytime somnolence or hyperactivity Antenatal/neonatal history: LBW, oligohydramnios, anoxia (ATN or renal vein thrombosis), umbilical artery catheterization, bronchopulmonary dysplasia. Past history: recurrent UTI, renal, cardiac, thyroid disorders Family history: hypertension, diabetes, dyslipidemia, obesity, premature cardiovascular or cerebro-vascular disease, hereditary renal or endocrine disease, neurofibromatosis, sleep apnoea. Risk factors: physical inactivity, dietary habits, smoking, alcohol, caffeine Drugs: eg. oral contraceptives, cyclosporin, steroids, tricyclic antidepressants, decongestants, excessive licorice, Ritalin, over-the-counter drugs or Chinese herbs, illicit drugs (cocaine, amphetamines), athletic performance-enhancing drugs including erythropoietin 3.2 Physical Examination General/Skin Height, weight, BMI: poor growth or obesity Pallor, facial or peripheral oedema Signs of neurofibromatosis, Turner, Williams, Tuberous sclerosis, Marfan’s, Cushing’s synd. Haemangioma in von Hippel-Lindau disease, Klippel-Trenaunay-Weber Signs of hyperthyroidism, SLE CVS BP measured both arms and a leg. If leg BP is lower than arm BP, suspect coarctation. Pulses of all extremities Bruits over large vessels in cranium (infants), neck, flank, abdomen Tachycardia, LV impulse, heart failure Eyes Retinal changes of hypertension, retinal vascular hamartoma (von-Hippel-Lindau disease) Hyperthyroid eye signs, EOM palsy Face / neck VII palsy, goitre ENT tonsillar hypertrophy, allergic rhinitis Abdomen Mass (Wilms tumour, neuroblastoma, phaeochromocytoma, polycystic kidneys, obstruction) Renal bruit Hepatosplenomegaly (infantile polycystic disease) Ambiguous genitalia / virilization 134 Section 3. Cardiovascular system 4. Investigations 4.1 Basic diagnostic tests for all a. Evaluation for cause Urea, creatinine, electrolytes Complete blood picture Urinalysis, urine culture, freshly voided centrifuged specimen x casts etc Renal ultrasound CXR, ECG b. Evaluation for comorbidity Uric acid, fasting lipids and glucose, including lipid fractions, fasting insulin in obese hypertensives to look for metabolic syndrome* HbA1c or glucose tolerance test in those with strong family history of Type 2 diabetes Drug screen if suspicious history Polysomnography if history of habitual snoring *National Cholesterol Education Program Definition for adults: 3/5 risk factors: Abdominal obesity (waist circumference ≥ 90cm for men, ≥ 80cm for women); hypertriglyceridemia > 1.69mmol/L; low HDL < 1.04 mmol/L in men, < 1.30 mmol/L in women; high BP ≥ 130/85 mmHg; high fasting glucose ≥ 6.1 mmol/L c. Evaluation for TOD Urine microalbumin (normal =2-30mg/mmol urinary Cr) Echocardiogram 4.2 Additional diagnostic tests as necessary Renin profiling (supine: overnight or supine for at least 30 minutes. Erect: ambulant > 60 minutes): low in mineralocorticoid diseases, monogenic HT, corticosteroid excess; high in 70-80% of RAS. Aldosterone - high in 85% patients with renal artery stenosis, in primary hyperaldosteronism - low in monogenic HT Plasma cortisol and urine steroid metabolites Plasma and urine VMA, HVA and catecholamines DMSA for scarring Renal vascular imaging: - Doppler flow studies of renal hilum - MAG3 or DMSA before and after ACE inhibitor - MRA or 3-dimensional or spiral CT angiography - Digital subtraction angiography (the gold standard) Others: renal vein renin sampling for RAS; caval sampling for catecholamines; MIBG or Indium-octreotide scan for phaechromocytoma; CT or MRI for adrenal and other tumours; genetic studies for monogenic hypertension 135 Section 3. Cardiovascular system Fig 1. Evaluation Algorithm for child with elevated BP (modified from 4th Report) Child with BP ─ ─ Prehypertensive Stage 2 HT Stage 1 HT BP ≥ (99% +5mmHg) BP 95% to < (99% +5mmHg) immediate referral to center with expertise in paediatric HT within 1 week or admission if patient symptomatic BP 90%to < 95% or ≥120/80mmHg even if < 90% 90 to95% Repeat BP over 3 visits Lifestyle changes ≥95% Repeat BP in 6 months Diagnostic tests (basic± additional) ± emergency treatment ABPM Consider basic diagnostic tests including evaluation for TOD* Sustained HT Whitecoat HT BP ≥ 95% or TOD Basic diagnostic tests including evaluation for TOD * if overweight, comorbid conditions, especially if younger, very high BP or no family history HT. Additional diagnostic tests if young child or evaluation suggestive of secondary causes Treat specific cause Secondary HT Primary HT Abbreviations: HT =hypertension, TOD=target organ damage 136 Lifestyle ± drug treatment Section 3. Cardiovascular system 5. Non pharmacologic Treatment of Hypertension For patients with borderline HT: a 6-month trial of salt and caloric restriction and a regular exercise program. 5.1 Salt restriction, weight loss and other dietary modifications Current recommendation of salt is < 1.5 g (~1/4 teaspoon) per day (2/3 already in the food itself). DASH diet emphasizes intake of fruits, vegetables, low-fat dairy, whole grains; and reduced intake of saturated fat and refined sugar. 5.2 Increase exercise and reduce sedentary behavioural patterns 30-60 minutes per day of continuous or accumulated aerobic physical activity (such as stationary bicycle or brisk walking) where they “work up a sweat” on most days. Sedentary activities (such as TV, computers, video games etc) to be limited to < 2 hours/ day. 5.3 Hypertension and sports participation (Table 2) Table 2 Recommendations for participation in competitive sportsa for the Pediatric Hypertensive patient 1. Children with significant hypertension (95th - 98th percentile) and no evidence of target organ involvementb can participate in all competitive sports. BP should be remeasured at least every 2 months to monitor the impact of competition. 2. Children with severe hypertension (≥ 99th percentile) who do not have target organ involvement should be restricted from competitive sports, particularly from high static sportsc, until their high blood pressure is controlled. 3. The eligibility for participation in competitive athletics for children with hypertension and target-organ damage or other cardiovascular diseases should be determined on an individual basis based on severity of both their hypertension and associated conditions. a. b. c. A competitive athlete is one who participates in sport that requires competition against others as a central component and requires vigorous training in a systematic fashion. TOD: 1) cardiac TOD = clinical, ECG or radiologic evidence of coronary artery disease; LVH by ECG or echo; left ventricular dysfunction or cardiac failure. 2) Renal TOD = pathologic proteinuria or subnormal GFR. 3) Eye = retinal hemorrhages or exudates. 4) cerebrovascular = history of TIA or stroke. 5) peripheral vascular = absence of one or more major pulses in extremities with or without claudication or an aneurysm. High static sports include field events (throwing), gymnastics, karate / judo, water skiing, weight lifting, body building, downhill skiing, wrestling, boxing, cycling, decathlon, rowing and speed skating. 5.4 Obstructive Sleep Apnea nasal steroids, montelukast, weight loss, T&A, orthodontic procedures or nasal CPAP 5.5 Other lifestyle modification: caffeine, cigarettes, alcohol, oral contraceptives Limit caffeine & caffeinated soft drinks. To cease / not start smoking and stimulant drugs, avoid drinking too much alcohol. Best to avoid oral contraceptives in adolescent girls. 137 Section 3. Cardiovascular system 6. Pharmacological treatment of hypertension 6.1 In children, there is scant evidence of long term benefits of lowering BP. Thus the decision to begin pharmacologic treatment in children is not taken easily. 6.2 6.3 Indications for drug therapy 1. symptomatic HT 2. secondary HT 3. hypertensive TOD 4. other conditions e.g. DM type 1 or 2, chronic or proteinuric kidney disease 5. consider in multiple cardiovascular risk factors (dyslipidemia, smoking, severe obesity) General principles of treatment 6.4 Aim lower BP to < 95th percentile. With co-morbidities such as diabetes or if TOD present, lower to <90th. With non-proteinuric CKD, to <75th. With proteinuric CKD: to <50th. Aim: fewest medications at the lowest daily dosage and frequency Start single drug at the lowest recommended dose; adjust up if target not reached in 4-8 weeks. Exception = hypertension is severe and symptomatic when IV therapy is indicated. Once highest recommended dose reached or side effects +, a second from a different class should be added, one with complementary mechanisms of action, such as ACEI + diuretic, vasodilator + diuretic or β-blocker. For essential hypertension in children generally, no specific class of drug is preferred. Diuretics and β-blockers have a long history of safety and efficacy. Newer classes including ACEI, CCB and ARB also effective and safe in children. Long-term treatment in children and adolescents: ABCD The British Hypertension Society launched ABCD algorithm for adults, the principles also apply to children. ACEI and ARB Beta-blocker Calcium Channel Blocker Diuretic Children generally respond better to drugs that block the renin system (A and B drugs) If combination treatment is needed, it is recommended to combine (A or B) with (C or D) The third step would involve triple therapy with either A+C+D or B+C+D. 6.5 Specific recommendations in choice of class of drug ACEI or ARB preferred in children with diabetes and microalbuminuria or proteinuric renal diseases. Combination of ACEI and ARB may have synergistic effects. ACEI and ARB may be the drugs of choice for patients with end-organ damage such as cardiac hypertrophy. β-blockers or CCB in hypertensive children with migraines. β-blockers for hypertension that persists after coarctation of aorta. Phaechromocytoma: cocaine or methamphetamine overdose need both alpha and beta blockade (phenoxybenzamine and propranolol). Inadequately blocked α-adrenergic activity can increase BP if β blocker is not complete. For athletic adolescents, avoid diuretics; β-blockers may also affect exercise 138 Section 3. Cardiovascular system 6.6 performance. CCB and ACEI or ARB are drugs of choice for athletes as they lower peripheral vascular resistance without affecting exercise capacity. In the treatment of Metabolic Syndrome (obesity, insulin resistance, hyperlipidemia and hypertension), where there is sympathetic over-stimulation, peripherally acting α1-adrenergic receptor antagonists like prazosin may be first choice. For infants, use shorter-acting agents for flexibility of dosage – propranolol instead of atenolol, captopril instead of enalapril. Once stable, the patient may be changed to the longer-acting antihypertensives. Additional notes on drug treatment Diuretics: High salt intake will negate the antihypertensive effect of thiazides. Loop diuretics generally less effective in BP control in patients with normal kidney function. Potassium-sparing diuretics reserved for patients with mineralocorticoid excess or to treat thiazide-induced hypokalaemia. ACEI and ARBs are both teratogenic. Adolescent girls should be counselled about birth control. Infants and young children are more sensitive to their antihypertensive effect and side effects including acute renal failure. Centrally acting α agonist clonidine may be useful in hypertensive urgencies or weaning off from IV drugs in hypertensive emergencies. It must be tapered slowly best over 6-10days, as rebound hypertension may occur. Staging of ABP levels in Children (AHA Scientific Statement 2014) Office BP* Mean Ambulatory SBP or DBP SBP or DBP Load, %§ Normal BP <90th %tile <95th %tile <25 White coat hypertension ≥95th %tile <95th %tile <25 ≥90th %tile or >120/80 mm Hg <95th %tile ≥25 <95th %tile >95th %tile ≥25 >95th %tile >95th %tile Classification Prehypertension Masked hypertension Ambulatory hypertension ‖ 25 –50 Severe ambulatory hypertension >95th %tile >95th %tile >50 (at risk for end-organ damage) %tile indicates percentile; BP, blood pressure; DBP, diastolic blood pressure; and SBP, systolic blood pressure. *Based on National High Blood Pressure Education Program Task Force normative data.101a Based on normative pediatric ABPM values in Appendix Tables A1 through A4. For either the wake or sleep period of the study, or both. For patients with elevated load but normal mean ambulatory BP and office BP that is either normal (<90th percentile) or hypertensive (≥95th percentile), no specific ambulatory BP classification can be assigned based on current evidence and expert consensus. These unclassified patients should be evaluated on a case-by-case basis, taking into account the presence of secondary hypertensiona or multiple cardiovascular risk factors. Some clinicians may prefer the term sustained hypertension rather than ambulatory hypertension. § ‖ ” 139 Section 3. Cardiovascular system Chapter 47 - Management of severe hypertension L Leung Definition Stage 2 hypertension (HT) = SBP or DBP > 99th percentile + 5 mmHg for sex, height percentile for age. Severe HT is not rigorously defined in children (adult is often taken as ≥180/110) but often taken as Stage 2 HT with severe symptoms. This is a level at which a patient, at presentation or in very near future, will likely manifest serious clinical signs, symptoms and target organ damage. It depends on the rate of BP rise and duration as much as the actual BP level. Hypertensive emergency is severe hypertension with life threatening symptoms +/- acute target organ damage, e.g. encephalopathy and seizures. Hypertensive urgency: Severe hypertension without target-organ damage or major symptoms, but may still have symptoms that are less significant like headache, nausea or vomiting. Symptoms and signs of hypertensive emergency: severe hypertension with retinopathy 27% (haemorrhage, papilloedema, anterior ischaemic optic neuropathy → may infarct optic nerve from ciliary arterial hypertensive damage, especially when BP is reduced too quickly) CNS: encephalopathy 25%, convulsions 25%, hemiplegia 8%, facial palsy 12% heart failure 13%, aortic dissection. renal failure GI haemorrhage microangiopathic haemolytic anaemia Symptoms and signs of hypertension in neonates: may be none tachypnoea, cardiomegaly, congestive heart failure seizures retinopathy lethargy, failure to thrive Conditions that may mimic hypertensive emergency/ where rapid BP reduction might be harmful (eg intracranial mass or injury/ NAI, coarctation of aorta) must be excluded. Also exclude causes where BP reduction should be achieved by other means (eg benzodiazepine and phentolamine for cocaine OD or analgesia for severe pain). Treatment of Hypertensive Emergencies and Urgencies Important to determine if HT is acute or chronic. If this history not available, lower BP slowly. General measures Assess ABC: avoid drugs like ketamine for rapid sequence intubation. Best obtain intra-arterial line for BP measurement, but do not delay treatment for this. If not available: auto-cycling oscillometric BP every 1-2 min. Seizures treated with anticonvulsants like lorazepam until seizures stop. 140 Section 3. Cardiovascular system Hypertensive emergency Requires urgent treatment to reduce within minutes to hours to avoid life-threatening complications. Goal = prevent HT-related damage by slow, controlled reduction of BP, minimize complications of over-rapid BP reduction due to HT induced abnormalities in autoregulation (cerebral ischaemia, ischaemic neuropathy of optic nerve, transverse ischaemic myelopathy, renal impairment). Best is to use IV antihypertensive medication given by continuous infusion in an intensive care setting. e.g. labetalol, sodium nitroprusside and nicardipine Two IV lines, one reserved for saline or plasma infusion to increase BP by volume expansion if sudden hypotension. Strategy is to decrease systolic pressure by ≤ 25% of original value over the first 6-8 hours after presentation, then gradually normalizing BP over the next 24-48 hours. Another well-tried strategy used by GOS is to reduce BP by one-third of the amount to be reduced in the first 12 hours, a further third over next 12 hours and to the proposed maintenance level over another 24 hours. Monitor carefully pupillary reactions, vision, consciousness and neurological findings. In ischaemic neuropathy of optic nerve, there will be loss of pupillary reflex, accommodation preserved, then saline should be given to rapidly increase BP. See Table 1 for antihypertensive drugs in children. Preferred drug for hypertensive encephalopathy is labetalol infusion. If contraindications (eg. Asthma, heart failure), IV nicardipine can be used, including in patients with hepatic and renal failure. Sodium nitroprusside is less used due to cyanide toxicity. Chronic oral anti-HT should be introduced in a conscious child after BP reasonable controlled within 24-48 hrs of starting infusions of anti-HT. Oral counterparts of IV drugs used are a good choice (e.g. oral labetalol, titrate every 6-12 hrs.), and rate of IV infusion can be slowly decreased. Prolonged use of IV anti-HT may result in Na and water retention and tachyphylaxis. Some patients, esp. those with normal kidney function, may have some volume depletion from pressure natriuresis due to very high BPs. In absence of signs of volume overload, some volume expansion with IV saline solution will help to suppress renin secretion and prevent significant hypotension once the vasodilating medications begin to act. Special situations in Hypertensive emergency Phaechromocytoma/ catecholamine-induced HT: α-blockers: phenoxybenzamine, phentolamine, prazosin. Pre-op management should include Na and vol repletion to prevent hypotension. Once α-blockade achieved, β- blockers may be used. CCB also useful. Renin-dependent hypertension (renovascular, renal parenchymal disease): ACEI except if main renal artery stenosis is suspected. Diuretics can be effective in severe HT caused by actue GN. Renal impairment with salt and water retention: UF, dialysis or high dose diruetics in those with residual urine output. Low renin hypertension (Apparent Mineralocorticoid Excess or Liddle) can present with life-threatening hypertension that only responds to specific agents that act on collecting tubules like triamterene or amiloride. Those with cerebral vascular disease or ↑ICP may need higher BP to maintain cerebral perfusion – not same approach. If need to use, labetalol is safer. 141 Section 3. Cardiovascular system Neonates and infants: little data. Need very careful and slow lowering. Nicardipine and nitroprusside has been used. Hypertensive urgency Important to assess whether elevated BP is acute or chronic event. If from acute process (eg PSGN): intervene within hours and IV treatment (eg. labetalol or hydralazine) is appropriate. If it is a chronic process, BP can be gradually reduced within a few days, using oral medications like clonidine (not for those with encephalopathy as it is centrally acting) or isradipine. It is preferred to use short-acting oral drugs initially so that any sudden drop in BP can be reversed more readily. Conversion to once daily agents can be made subsequently. The Fourth Report does not recommend the use of short-acting nifedipine for HT emergencies due to the unpredictable degree of BP reduction. In HT urgency, if IV access cannot be obtained quickly, it has been used judiciously with the lowest effective dose. TABLE 1. Antihypertensive Drugs for Management of Severe Hypertension in Children 1-17 Years Old Drug Class Dose* Route Onset Duration Comments Contraindicatied in 2nd or 3rd degree heart block, low cardiac output. Asthma and overt heart failure are relative contraindications. Side effect: nasal congestion, rash, pruritus, nausea, vomiting. Severe hepatocellular damage has been reported. May mask symptoms of hypoglycemia. May cause reflex tachycardia, phlebitis. Intravenous drugs for HT emergencies and urgencies in children Labetalol α-1 and - Blocker β Infusion:start 0.25-0.5 mg/kg/hr, to maximum 3.0 mg/kg per hr IV bolus or infusion 5-10 min Peak 5-15 min 2-6 hrs T½ 3-5h Nicardipine (time of writing: N/A in HK) Calcium channel Blocker (dihydropy ridine) Bolus 30mcg.kg up to 2mg/dose Infusion: 0.5-4mcg/kg per min IV bolus or infusion 5-10 min 100-500mcg/kg per min IV infusion Within secs 30min-4 hrs (↑with time of infusion) T½ 1015min 10-20 min T½ 10min 0.5 -10mcg/kg per min. Increase slowly (risk of tachycardia) and discontineu over 15-30 min to prevent rebound effect. IV infusion 1-2 min Esmolol Sodium nitroprusside β- Blocker Direct Vasodilator (arterioles & venules) ↓TPR & venous return (afterload & preload). Used in Protect from light. 142 < 10 min Needs constant infusion. May cause profound bradycardia. Avoid if history of asthma and in acute decompensated heart failure. Metabolism independant of kidney and liver. Monitor cyanide levels with prolonged use (>48 hours) or in renal/hepatic insufficiency; or coadminister with sodium thiosulfate. Cyanide iinhibits cellular oxidative metabolism. Excessive concentrations can cause tachycardia, sweating, hyperventilation, caridaic arrhythmias and metabolic acidosis. Tachyphylaxis with Section 3. Cardiovascular system acute pulmonary edema. Hydralazine Direct Vasodilator (arterial) 0.2-0.6 mg/kg per dose, max single dose 20mg. IV, IM 10-30 min Peak 10-80 min after IV 2-6 hrs, up to 12hrs – unpredic table. Enalaprilat ACE inhibitor 5-10 mcg/kg/dose up to 1.25 mg/dose IV bolus 15 min 4-6 hrs prolonged use. Do not use in patients with vitamin B12 deficiency, impaired liver function, Leber’s optic atrophy. Caution in hypothyroid pts. Should be given every 4 hours when given IV bolus. Recommended dose is lower than FDA label. Must have 2 large bore IV cannulae: NS can be given if BP reduced too quickly. Causes reflex tachycardia, headaches, flushing and fluid retention. Effect less predictable, more difficult to titrate. Can be given IM: useful when immediate need to lower BP but no IV access. May cause prolonged hypotension and acute renal failure in neonates and hypovolemic patients. Avoid if severe renal artery stenosis suspected, especially if bilateral. Oral drugs for treatment of hypertensive urgencies in children Drug Class Dose* Route Onset Duration Comments Clonidine Central α2-agonist po 15-30 min 6-10 hrs Side effects include dry mouth and sedation. Avoid in encephology. Can be used in renal failure (no need dose adjustment), esp in older children and adolescents. Narrow safety profile in young children. Isradipine Calcium channel blocker po 1 hour Peak 2-3hrs 12 hrs Stable suspension can be compounded and used in infants. Rapid metabolism in children, usu need 3-4x daily. Hydralazine Direct vasodilator (arterial) Direct Vasodilator (arterial) Limited info. In adults, initial dose 100-200 mcg followed by repeated hourly doses of 50-100 mcg until BP goal reached (max 800mcg total dose). In child, initial 1-2 mcg/kg /dose titrate hourly to BP goal (max 800mcg total dose or 25mcg /kg/day in divided doses) 0.05-0.1 mg/kg per dose, up to 5mg/dose. Lower doses in <2yr olds. (0.03-0.05mg/kg) 0.25 mg/kg per dose up to 25 mg max single dose 0.1-0.2 mg/kg per dose up to 10mg/dose po 30min 2-8 hrs Variable response po 30 mins 2-5 days Most potent oral vasodilator, long-acting. Minoxidil Ref. Chandar 2012, Flynn 2009, Patel 2005 143 Section 3. Cardiovascular system Chapter 48 - Management of Kawasaki disease KL Kwok, Maurice Leung (I) Classical diagnostic criteria: 1. Fever of at least 5 days duration 2. Presence of 4 of the following 5 principal clinical features Bilateral conjunctival injection Oral changes including red and/or fissured lips, strawberry tongue, injected oral mucosa and pharynx Extremity changes including edema and/or erythema of hands and/or feet in the acute phase, periungual desquamation in the convalescent phase Polymorphic rash Cervical lymphadenopathy, at least 1.5 cm diameter 3. Illness not explained by other known disease process. Incomplete Kawasaki Disease# (see diagram) Fever ≥ 5 days with < 4 principal clinical features Echocardiographic or angiographic abnormalities such as Coronary arteries: perivascular brightness, lack of tapering, ectasia or aneurysm Decreased LV function, mitral regurgitation, pericardial effusion 1. Diagnosis can be flexibly made on D4 (for earlier treatment) in the presence of ≥ 4 principal clinical features 2. Consider Kawasaki disease as differential diagnosis in young children with unexplained fever ≥ 5 days with any principal clinical features. Consult cardiologist / Kawasaki disease specialist at low threshold. 3. Commencement of treatment may have to be considered on an individual basis for cases with insufficient diagnostic criteria. # The term “Atypical Kawasaki Disease” is reserved for those with features that not usually present in KD such as renal impairment. (II) The following may help in diagnosing Incomplete Kawasaki Disease: A. Supplemental Laboratory criteria (if >= 3 criteria, can treat before echo) Albumin <=30g/L Anemia for age ALT elevation Platelet after D7 >= 450 WCC >= 15 Urine >= 10 WCC/HPF 144 Section 3. Cardiovascular system B. Positive Echo* (any one of THREE) 1. Z score of LAD or RCA >= 2.5 2. Coronary arteries meet Japanese Ministry of Health criteria (>3mm in <5yo or >4mm in ≥5yo; diameter of a segment = 1.5 x adjacent segment) 3. >= 3 other features: Perivascular brightness Lack of tapering Decreased LV function Mitral regurgitation Pericardial effusion > Z score of LAD or RCA > 2 but <2.5 *internal diameter: inner edge to inner edge Diagnostic Pathway of KD Fever ≥ 5 days and 2 or 3 clinical criteria Assess Patient Characteristics Consistent with KD Persistent Fever Inconsistent with KD Assess Laboratory Tests KD Unlikely CRP ≥3.0 mg/DL and/or ESR ≥ 40 mm/hr CRP <3.0 mg/DL and ESR <40 mm/hr Follow Daily Fever continues for 2 days Fever resolves No Peeling No f/u ≥3 Supplemental Laboratory Criteria <3 Supplemental Laboratory Criteria Echo Typical Peeling Echo Treat and Echo Echo + Echo Fever Persists Fever Abates Newburger JW et al, Pediatrics 2004 Dec;114(6):1708-33 Repeat Echo Consult KD Expert 145 KD Unlikely Treat Section 3. Cardiovascular system Initial investigations: 1. CBP, ESR, blood culture, LRFT, lipid, viral titre (leukocytosis with neutrophilia and immature forms; raised ESR; raised CRP; anaemia; abnormal plasma lipids; hypoalbuminaemia; hyponatremia; thrombocytosis after week 1 or thrombocytopenia/DIC; sterile pyuria; raised serum transaminases; raised serum GGT; pleocytosis of CSF; leukocytosis in synovial fluid) 2. ECG: arrhythmia, prolonged PR interval or non-specific ST and T wave changes 3. Echocardiogram in the acute phase Treatment in the acute phase when fever is still present (within 10 days ** of illness): 1. IVIG 2g/kg infused over 12 hours with blood pressure and pulse rate measured hourly and preferably cardiorespiratory monitoring. Infusion rate can be slowed down (> 24 hours) when occurrence of allergic reaction (e.g. chills and rigors or hypotension) or presence of cardiac and renal insufficiency. Additional doses of IVIG may be given if fever does not subside promptly after the initial dose or recurs afterwards. **If possible, treatment to be given within 7 days of illness. For incomplete Kawasaki, IVIG can be given before D5, but it may be associated with an increased need for IVIG retreatment. IVIG should be given even after the 10th day of illness (missed earlier) if they have either persistent fever without other explanation or aneurysms and ongoing systemic inflammation, as manifested by elevated ESR or CRP. 2. Aspirin 30-50 mg/kg oral in 3-4 divided doses with food. Routine prescription of antacid is not required. Aspirin can be changed to low dose (Aspirin 3-5 mg/kg/day for 8 weeks) when fever has subsided for 48 hours. Avoid Ibuprofen as it will decrease anti-platelet function of aspirin. Antacids may decrease efficacy of aspirin. Aspirin can be omitted in the acute phase if there are contraindications such as G6PD deficiency, bleeding tendency or aspirin-induced asthma. Mild to moderate elevation of transaminases commonly found in Kawasaki disease is not a contraindication to use of aspirin. 3. Steroids may be considered for cases with persistent/ recurrent fever after receiving ≥ 4 g/kg of IVIG. The most commonly used regimen is IV pulse methylprednisolone 30 mg/kg over 2-3 hours, once daily for 1-3 days, followed by prednisolone 2mg/kg/day po until D7 Or until CRP normalizes; then wean over in next 2-3 weeks. Echo performed at 1. Diagnosis 2. 2 weeks 3. 6-8 weeks a. Saccular if axial and lateral diameters are nearly equal b. Fusiform if symmetrical dilatation with gradual proximal or distal tapering c. Ectasia = dilatation 146 Section 3. Cardiovascular system Definition of coronary artery abnormalities: Either Japanese Ministry of Health Criteria1. 3mm in < 5 years; 2. 4mm in > 5 years; 3. diameter of a segment = 1.5 x adjacent segment OR Z score > 2 Long term management is according to the following protocol depending on the coronary artery involvement: 1. No CAA or only transient dilatation Aspirin 3-5 mg/kg/day for 8 weeks No restriction of physical activity beyond 8 weeks FU and Echo at 2 weeks; 2, 6 and 12 months Then yearly FU without Echo 2. CAA at acute stage but resolved Aspirin 3-5 mg/kg/day for 8 weeks No restriction of physical activity beyond 8 weeks FU and Echo at 2 weeks, 4 weeks; 2, 6, 12 months Then yearly FU without Echo 3. CAA < 8mm Aspirin until CAA resolved Recommendation on physical activity guided by stress test / myocardial perfusion scan Competitive sport discouraged FU and Echo at 2 weeks, 4 weeks; 2, 6, and 12 months, and then yearly Myocardial perfusion scan every 2 years Angiogram at 12 months if CAA persists or if Echo shows stenosis or if perfusion scan abnormal 4. Giant CAA ≥ 8mm Long term aspirin +/- warfarin Only recreational sport allowed, level to be guided by perfusion scan / stress test FU and Echo at 2 weeks, 4 weeks; 2, 6, and 12 months, and then yearly Myocardial perfusion scan yearly Angiogram at 12 months or if symptoms or results of other tests suggest coronary artery stenosis 5. CAA + obstruction Long term aspirin +/- warfarin Only recreational sport allowed, level to be guided by perfusion scan / stress test FU and Echo at 2 weeks, 4 weeks; 2, 6, and 12 months, and then yearly Myocardial perfusion scan yearly Angiogram for evaluation of symptoms or previous intervention Patients with contraindications to aspirin can be given dipyridamole (persantin) instead at a dosage of 5 mg/kg/day in 2-3 divided doses in multiple of the 25mg tablet. 147 Section 3. Cardiovascular system Patient counselling: 1. General heart health: diet, weight control, blood pressure 2. Exercise recommendation (certifying letter) 3. Yearly influenza vaccination for children on long term aspirin and > 6 months of age 4. Measles and varicella vaccine should be delayed until 11 months after the infusion of IVIG. Or MMR can be given at 6 months and then another dose 11 months from receiving IVIG to have better protection to the child from measles in the interim period. Aspirin should be avoided for 6 weeks after administration of varicella vaccine and aspirin to be replaced by dipyridamole. 148 Section 3. Cardiovascular system Risk Level I II III IV V Coronary No abn at any stage Transient ectasia / dilatation >3mm- <6mm or z-score = 3-7 in ≥1 coronary artery ≥6mm, including giant aneurysm, multiple (segmental) or complex aneurysm Without obstruction Coronary artery Obstruction Anti-platelet therapy beyond 6-8 weeks × Aspirin + clopidogrel for multiple and complex aneurysm × Aspirin Aspirin +/- warfarin Aspirin + warfarin for giant aneurysm (INR = 2-2.5) Avoid contact / high impact sports because of bleeding risk while on aspirin Physical activity Counselling, ECG, Echo No restriction beyond 6-8 weeks Every 5 years No restriction 0-10 years old, then myocardial perfusion test to guide recommendation Every 3-5 yrs Myocardial Perfusion Test × Coronary angiography Not recommended - Annual stress test, myocardial perfusion test to guide recommendations. - Recreational non-contact sports encouraged if no evidence of stress-induced myocardial ischemia Beta-blocker to reduce myocardial oxygen consumption Annual 6 monthly Every 2 years in patients >10 yrs Only if myocardial ischemia demonstrated by stress test Annual myocardial perfusion test + screening for risk factors for atherosclerosis Done 6-12 months after recovery to address therapeutic options of bypass grafting or catheter intervention and identify extent of collateral perfusion (sooner if clinically indicated) Contact sports include rugby, karate, hockey and wrestling High impact sports include netball, step aerobics, basketball, football, boxercise, squash and tennis. References: Newburger JW et al. Circulation 2004 Eleftheriou D et al. Arch Dis Child 2014 149 Section 3. Cardiovascular system Chapter 49 - Treadmill (Exercise stress test) YM Fu, KL Kwok Indications: 1. Exertional chest pain 2. Arrhythmia a) Ventricular arrhythmias increasing in frequency with exercise may require therapy. If the arrhythmias can be abolished by exercise and are not associated with organic cardiac disorders, they are generally benign. b) AV block: if it worsens with exercise, it may require therapy. 3. Aortic valve disease : a) Aortic stenosis: ischaemic changes on ECG during exercise may be an indication for surgery b) Aortic regurgitation: ST changes or failure to raise HR with exercise may indicate LV dysfunction and may need valve replacement 4. Post-operative evaluation: a) Cyanotic congenital heart diseases: those which develop multiform PVC or VT may lead to sudden death and require therapy (either antiarrhythmic therapy or surgery). b) Post-coarctectomy patients who develop an excessive increase in BP with exercise may need antihypertensive treatment. 5. Exercise prescription for participation in vocational, recreational, and competitive activities. Absolute Contraindications Recent significant change in the resting ECG suggesting infarction or other acute cardiac 1 event 2 Recent complicated myocardial infarction 3 Unstable angina 4 Uncontrolled ventricular arrhythmia 5 Uncontrolled atrial arrhythmia that compromises cardiac function 6 Third degree AV block without pacemaker 7 Acute congestive heart failure 8 Severe aortic stenosis 9 Suspected or known dissecting aneurysm 10 Thrombophlebitis or intracardiac thrombi 11 Active or suspected myocarditis or pericarditis 12 Recent systemic or pulmonary embolus 13 Acute infections 14 Significant emotional distress (psychosis) 150 Section 3. Cardiovascular system Relative Contraindications 1 Resting diastolic blood pressure > 115 mmHg or resting systolic blood pressure > 200 mmHg 2 Moderate valvular heart disease 3 Known electrolyte abnormalities (hypokalaemia, hypomagnesaemia) 4 Fixed-rate pacemaker (rarely used) 5 Frequent or complex ventricular ectopy 6 Ventricular aneurysm 7 Uncontrolled metabolic disease (e.g. diabetes, thyrotoxicosis or myxoedema) 8 Chronic infectious disease (e.g. mononucleosis, hepatitis, AIDS) 9 Neuromuscular, musculoskeletal, or rheumatoid disorders that are exacerbated by exercise 10 Advanced or complicated pregnancy Source: From ACSM Guidelines for Exercise Testing and Prescription ed 5, Williams & Wilkins, Baltimore, 1995, p.42, with permission. Interpretations: Symptoms: Anginal chest pain, fatigue, dizziness, shortness of breath Blood pressure: normal response is elevated systolic BP and little change on diastolic BP; failure to increase systolic BP or falls by ≥ 10mmHg indicates LV dysfunction. Heart rate (HR): rises with exercise intensity; maximal HR = 220 - age; arbitrary target is a rise of > 85% maximal HR. Exercise tolerance Ventricular arrhythmia during exercise or the recovery phase ST changes: the most common manifestation is ST segment depression (≥ 1 mm horizontal or downsloping); ST segment elevation (uncommon in the absence of prior infarction, but implies severe transmural ischaemia, can locate the site of involvement) Not useful in 1. Chest pain not likely cardiac origin 2. Screening for healthy children before athletic participation 3. Premature atrial contraction (PAC) or premature ventricular contraction (PVC) in otherwise health children Booking Preparation: Consent: inform the risk of arrhythmia or myocardial infarction, may need resuscitation Booking form (exercise challenge) Baseline ECG, together with the consent and booking form to N8 ward clerk (Mr Wong) May need Echo before treadmill in case to rule out LVOT obstruction Ask patient to wear sports shoes and avoid heavy meal before treadmill 151 Section 3. Cardiovascular system Chapter 50 – Treatment regime for patients with heart diseases that mandate prophylactic antibiotics KL Kwok, Maurice Leung According to Infective Endocarditis (IE) Prophylaxis Guideline 2010: Cardiac Condition Associated With the Highest Risk of Adverse Outcome From Endocarditis for Which Prophylaxis With Dental Procedures is recommended. 1. Prosthetic cardiac valve or prosthetic material used for cardiac valve repair 2. Previous Infective Endocarditis 3. Congenital Heart Disease (CHD) * Unrepaired cyanotic CHD, including palliative Shunts and conduits Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure # Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) 4. Cardiac Transplantation recipients who develop cardiac valvulopathy. * Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of CHD. # Prophylaxis is recommended because endothelialization of prosthetic material occurs within 6 months after the procedure. Regimes for Dental Procedures Dental Procedures for Which Endocarditis Prophylaxis is recommended All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa* • The following procedures and events do not need prophylaxis: routine anesthetic injections through noninfected tissue, taking dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, placement or orthodontic brackets, shedding of deciduous teeth, and bleeding from trauma to the lips or oral mucosa. 152 Section 3. Cardiovascular system Regime: Single Dose 30-60 min Before Procedure Situation Agent Adults Children Oral Amoxicillin 2 grams 50 mg/kg Ampicillin or Ceftriaxone* Cephalexin* or Clindamycin or Axithromycin/ Charithromycin 2 grams IM or IV 50 mg/kg IM or IV 1 grams IM or IV 2 grams 50 mg/kg IM or IV 50 mg/kg 600 mg 20 mg/kg 500 mg 15 mg/kg 1 grams IM or IV 50 mg/kg IM or IV 60 mg IM or IV 50 mg/kg IM or IV Unable to take oral medications Allergic to Penicillins or Amoxicillin - oral Allergic to Penicillins or Ceftriaxone* Ampicillin and or unable to take oral Clindamycin medication IM indicates intramuscular, IV intravenous *Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema or urticaria with penicillins or ampicillin. Antibiotic prophylaxis is recommended for procedures on respiratory or infected skin, skin structures or musculoskeletal tissue only for patients with underlying cardiac conditions mentioned above. Antibiotic prophylaxis soley to prevent infective endocarditis is NOT recommended for gastrointestinal (GI) or genitourinary (GU) tract. An antibiotic for prophylaxis should be administered in a single dose before the procedure. If the dosage of antibiotic is inadvertently not administered before the procedure, the dosage may be administered up to 2 hours after the procedure. However, administration of the dosage after the procedure should be considered only when the patient did not receive the pre-procedure dose. 153 Section 3. Cardiovascular system Chapter 51 – ECG criteria for LVH & RVH & prolonged QT interval KL Kwok Criteria for LVH: 1. Left axis deviation for patient’s age 2. a. R in I, II, III, aVL, aVF, V5 or V6 greater than the upper limits of normal for age b. S in V1 or V2 greater than the upper limits of normal for age 3. R/S ratio in V1 and V2 less than the lower limits of normal for the patient’s age 4. Q in V5 and V6, 5mm or more, coupled with tall symmetric T waves in the same leads (volume overload) 5. Wide QRS-T angle with T axis outside the normal range indicates a strain pattern. This is manifested by inverted T waves in lead I or aVF. Simplified version of ECG definition for LVH: R/S (V1) R (V6) mm S (V1) mm 0-7 days < 0.1 > 10 >20 7-30 days <1 > 15 > 10 1-3 months < 0.3 > 20 > 15 3-12 months < 0.1 > 20 > 15 1-3 years < 0.1 > 20 > 25 3-16 years < 0.02 > 25 > 25 Criteria for RVH: 1. Right axis deviation for patient’s age 2. a. R in V1, V2, or aVR greater than the upper limits of normal for patient’s age b. S in I and V6 greater than the upper limits of normal for the patient’s age 3. Abnormal R/S ratio in favour of the RV in the absence of BBB a. R/S ratio in V1 and V2 greater than the upper limits of normal for age. b. R/S ratio in V6 less than 1 after 1 month of age 4. Upright T in V1 in patients more than 3 days of age, provided that T is upright in the LPLs (V5, V6). Upright T in V1 is not abnormal in patients 6 years or older. 5. A q wave in V1 (qR or qRs pattern) suggests RVH. 6. Wide QRS-T angle with T axis outside the normal range indicates a strain pattern. Simplified version of ECG definition for RVH: R/S (V1) R (V1) mm S (V6) mm 0-7 days > 10 > 25 > 10 7-30 days > 10 > 25 > 10 1-3 months >6 > 20 > 10 3-12 months >4 > 20 > 10 1-3 years >4 > 20 >5 3-16 years >2 > 10 >5 Criteria for RVH in Newborn: S waves in lead I ≥ 12 mm R waves in aVR ≥ 8 mm Abnormalities in V1: 1. Pure R wave (no S wave) in V1 greater than 10mm 2. R in V1 ≥ 25 mm 3. qR pattern in V1 (also in 10% of healthy newborn) 4. Upright T waves in V1 in newborns more than 3 days of age with upright T in V6 RAD greater than +180º 154 Section 3. Cardiovascular system Criteria for bi-ventricular hypertrophy: 1. Positive voltage criteria for RVH and LVH in the absence of BBB or WPW syndrome 2. Positive voltage criteria for RVH or LVH and relatively large voltages for the other ventricle 3. Large equiphasic QRS complexes in two or more of the limb leads and in the mid-precordial leads (V2 through V5), called Katz-Wachtel phenomenon Prolonged QT interval: Corrected QT interval > 0.44 sec Higher risk for fatal arrhythmia if QTc > 0.53 sec Diagnostic criteria LQTS—1993 Schwartz ECG findingsa (A) QTcb ≥480 ms 460–479 ms 450–459 ms (in males) 3 points 2 points 1 point (B) Torsade de pointesc 2 points (C) T wave alternans (D) Notched T wave in three leads 1 point 1 point (E) Low heart rate for aged 0.5 point Clinical history (A) Syncopec With stress Without stress (B) Congenital deafness 2 points 1 point 0.5 point Family historye (A) Family members with definite LQTSf 1 point (B) Unexplained sudden cardiac death below age 30 among immediate family members a 0.5 point In the absence of medications or disorders known to affect these ECG features. Calculated by Bazett's formula, where QTc = QT/√ RR. c Mutually exclusive. d Resting heart rate below the second percentile for age. e The same family member cannot be counted in A and B. f Definite LQTS is defined by an LQTS score ≥4. Scoring: ≤1 point, low probability of LQTS; 2–3 points, intermediate probability of LQTS; ≥4 points, high probability of LQTS. b 155 Section 3. Cardiovascular system Drugs affecting QT interval (List of drugs is not exhaustive) Common Drugs used in children that prolong QT interval and/or induce Torsade De Pointes 1. Anti-arrhythmics— e.g. Amiodarone, Flecainide , Procainamide, Quinidine, Sotalol 2. Antibiotics— e.g. Clarithromycin, Erythromycin, Levofloxacin, Azithromycin 3. Others: e.g. Octreotide, Salmeterol Drugs to be avoided in patient with Long QT interval: 1. Bronchodilator— e.g. Albuterol, Salmeterol, Terbutaline 2. Antiviral— e.g. Amantadine 3. Catecholamine— e.g. Dobutamine, Adrenaline, Nor-adrenaline 4. Decongestant— e.g. Ephedrine, Phenylephrine, Phenylpropanolamine, Pseudoephedrine 5. Antibiotics— e.g. Azithromycin 156 Section 4. Central nervous system Section 4: Central nervous system 157 Section 4. Central nervous system Chapter 52 - Acute management of post-neonatal convulsion S Cherk 1. Monitor vital signs 2. Maintain airway, protect from injury and place the child in semi prone position. Apply suction for nasal or oral secretion if any 3. Give oxygen supplement during seizure until full post-ictal recovery of conscious state 4. If convulsion lasts for more than 5 minutes: a) If IV access present or attained readily IV Lorazepam 0.1 mg/kg/dose (maximum 4 mg/dose), may repeat dose 10 min later, max total dose 8 mg in adolescent b) If no IV access give rectal diazepam 0.5 mg/kg/dose or consider buccal midazolam 0.4-0.5 mg/kg/dose (method #) (Panayiotopoulos 2007) Refer to protocol of management of generalized convulsive status epilepticus if prolonged convulsion. 5. Detailed history and examination to look for underlying cause of convulsion. # Method - child lie on side in coma position - open lips, trickle midazolam from syringe into inside of cheek (dependent side) between the cheek and lower gum. - no need to open jaw 158 Section 4. Central nervous system Chapter 53 - Generalized convulsive status epilepticus (Excluding neonates) S Cherk Airway – Recovery position, suction (Yankauer sucker if food in mouth) Breathing – SpO2 monitor, high flow O2 by mask Circulation – AR/ BP/Capillary return Immediate IV Access+ Blood taking (Glucostix, blood sugar, e, Ca, Mg (<1yr) , CBP, blood gas, L/RFT, NH3 +/- blood culture, +/- toxicology/anticonvulsant level),save plasma 1-2 ml & urine 20 ml for later analysis ANTICIPATION aim to abort seizure as quickly as possible to prevent status epilepticus SEIZURE duration ≥ 5 min (prolonged seizure/ impending status) 1. IV Lorazepam 0.1 mg/kg Max 4mg/dose, over 60sec Rpt dose at 5-10 min if still Sz If no IV access Diazepam PR 0.5mg/kg or Buccal midazolam 0.4-0.5mg/kg Rpt dose at 10 min if still Sz & no IV access SEIZURE continues at 25 minutes (Impending status) To PICU No IV access IV access + 2. * IV Phenytoin 20 mg/kg in NS over 20 min or IV Phenobarbitone if already on Phenytoin, 20mg/kg over 15 min Paraldehyde PR 0.4ml/kg max 5ml if < 50kg max 10ml if ≥ 50kg AND PR paraldehyde if not already given 0.4ml/kg (+ same volume Olive oil) glass syringe + feeding tube SEIZURE CONTINUES AT 45 minutes (Established Status Epilepticus by 30 min) Patient not on maintenance Benzodiazepine Patient already on maintenance Benzodiazepine • Thiopentone – Loading IV 3-5 mg/kg bolus – Then infusion 3-5 mg/kg/hr – EEG iso-electric / burst suppression – Intubate & ventilate before loading IV Midazolam Loading 0.1-0.5 mg/kg Infusion 1 -2 mcg/kg/min, incr by 1-2mcg/kg/min every 5-10 min until seizure stops Usu dose range :1-30 mcg/kg/min C 159 Section 4. Central nervous system Other IV anticonvulsants to consider: -IV Levetiracetam 20-60mg/kg @2-5 mg/kg/min -IV Valproate 20-40mg/kg IV @1.5-3 mg/kg/min ( but hyperNH3, pancreatitis, hepatotoxicty, decr Plt) General precautions: - close monitor cardio-respiratory function & blood gas/ electrolytes - ensure large vein IV access - be prepared for intubation & ventilation and hemodynamic support Consider IV pyridoxine /enteral pyridoxal phosphate in children < 3yr with unknown aetiology: - IV Pyridoxine 100 mg/dose + 2nd dose 100 mg within 30 minutes, can repeat up to total 500mg preferrably under EEG monitor (prepare for intubation /ventilatory support as risk of apnea ) followed by enteral pyridoxine 5-15mg/kg/day q12h if response - if no response, consider trial enteral Pyrioxal Phosphate(PLP) 30 mg/kg/d in 3 divided doses - send specimens: - blood pipeocolic acid -Urine and plasma xαAASA( immediate freezing needed) -Urine x vanilly-lactic acid - when patient stable and no C/I for LP : send CSF-HVA,HIAA, AA’s ( threonine, glycine) - continue Pyridoxal phosphate if seizure stopped after pyridoxine/PLP until Ix results incl above Biochemistry Ix reviewed by and discussed with Neuro Team *- watch hypotension /arrhythmia- slow down infusion rate if mild bradycardia - C/I in second degree heart block / severe hypotension/ TCA anti-depressant toxicity - caution use in Dravet Syndrome 160 Section 4. Central nervous system Chapter 54 - Febrile convulsion MS Choi, S Cherk Background: Febrile convulsion occurs in 2-5% of all children. Risk of recurrent febrile seizure following a first febrile seizure is around 30%. 50-75% & 90% recurrence occurs within one year & two year of initial seizure respectively. Definition: Febrile convulsion is defined as convulsion occurring in a child, aged 6 months to 60 months, associated with fever without evidence of intra-cranial infection or other causes and who is otherwise neurologically normal. Simple febrile convulsion: It is defined as primary generalized convulsion lasting less than 15 minutes and not recurring within 24 hours. Complex febrile convulsion: It is defined as focal or prolonged (>15 minutes), and/or more than one convulsion in 24 hours. Investigation: 1. CBP, D/C, CRP 2. RFT / Calcium / Glucose / H’stix / Blood gas 3. ± Blood culture 4. ± Urine for R/M and culture 5. ± CXR 6. Lumbar puncture is indicated if suspected CNS infection 7. EEG is rarely indicated in the management of a simple febrile convulsion 8. CT brain is not necessary in most cases except for the following situation: - Papilloedema - Cranial nerve palsy - Persistent focal neurological signs - Marked depression in mental status or comatosed Management of febrile convulsion: 1. Convulsion chart 2. Neuro-observation 3. Monitor vital signs 4. Maintain airway, protect from injury and place the child in semi prone position 5. Give oxygen supplement during seizure until full post-ictal recovery of conscious state 6. Apply suction for nasal or oral secretion if any 7. Treat fever by tepid sponging and syrup panadol 10-15 mg/kg/dose Q4H prn 8. Identify the focus of infection and treat accordingly 9. For acute treatment of convulsion, please refer to chapter 49 10. Refer to protocol of management of generalized convulsive status epilepticus (chapter 53) if prolonged convulsion 161 Section 4. Central nervous system Prophylaxis for recurrent febrile convulsion: - Intermittent diazepam prophylaxis seems to be effective in reducing recurrence rate if sufficient doses are given - In selected cases, give oral Valium 1 mg/kg/day Q8H for consecutive 6 doses whenever the rectal temperature is ≥ 38.5oC - Side effects of diazepam include ataxia, lethargy and irritability. Alert parent to monitor the child regularly in case the underlying infection may be masked due to lethargy from the effect of diazepam. Prognosis: - Prognosis in terms of intellectual outcome is good - Recurrence risk is 50% if febrile convulsion occurs in the first year of life Prediction for seizure recurrence Major : Early age of first seizure (<18 mo) Positive FH of febrile seizure (1st degree relative) Others : - Low degree of fever prior to initial seizure (<38˚C) - Brief duration between fever onset and initial seizure (<12 hour) Risk ≥70% vs ≤ 20% (all 4 risk factors above vs none) - Abnormal neurologic background - Positive F/H afebrile seizure (1st degree relative) - Seizure recurrence within same febrile illness Risk of later epilepsy: - Risk following a simple febrile seizure: - 1-2.4 % (vs 0.4% in general population) - Risk of epilepsy following a complex febrile seizure depends on number of risk factors present: Risk factor for developing epilepsy: - * Preexisting neurological abnormality - * Family history of afebrile convulsion - * Complex first febrile convulsion When a single complex feature present: risk 6-8% When all three complex features* present: 49% Immunization: No contraindication for the current standard vaccination 162 Section 4. Central nervous system Chapter 55 - Approach to a child with decreased conscious level (excluding neonates) S Cherk Ensure child is maximally aroused from sleep when assessed. -Excluded : -children with known condition for episodes of reduced conscious level ( e.g. epilepsy, DM) where management plan available -children whose baseline GCS is <15 GCS <15 Assess A,B,C ; Give O2 Consider intubation if : airway obstruction/airway compromised; RR inadequate for ventilation; SaO2 <92% despite high flow O2/airway opening maneuvers; signs of shock despite 40 ml/kg fluid; exhaustion; GCS≤8 or deteriorating; signs of ↑ICP Assess for -↑ICP: (GCS, pupils, fundi, bradycardia, HT, irregular breathing) -ongoing seizure Monitor vital signs Monitor GCS Consider ICU care if GCS≤10 / deteriorating / fluctuating GCS / suspected ↑ICP/ potential need resp support Core Ix: Dextrostix Blood x gases, gluc (even if D’stix N), U&E, Ca, Mg LFT,CBP Blood culture, NH3,lactate X5-6 ml ( to be kept in fridge) X 3ml Lithium blood-sent in ice for centrifuge for AA & carnitine P/E, in particular Urine x bedside multi-stix Rash (purpuric, vesicular) ; odour X RM, culture Subtle motor seizure( mouth, digit, eyelid twitch) x 20 ml for toxicology ( send out) Involuntary movements/ abn posture X 20 ml to be kept in fridge Wounds/ bites/ injection sites CT scan+/- contrast to look for intracranial Signs of raised ICP SOL/swelling/ brain shift if: - condition stable and safe for transfer (need MO escort with readiness for O2,airway support and intubation) Identify problems and manage accordingly ( these may be aetiology effects ) - consider priororintubation Hx, particular attention to includes: Alternating periods of consciousness PH similar episodes Recent illness (rash- VZV, measles) animal or insect bites steroid intake/adrenal insufficiency Any prev FHx infant deaths/ALTE /consanguinity 163 Section 4. Central nervous system Problem list ( aetiology or complications) shock sepsis trauma CNS infection or inflamm ation ↑ICP Prolonged convulsion Post convul -sion (if >1hr) Meta-bolic e.g. e-disturba nce Hypogly DKA HyperNH3 HT Others Drugs Unknown# If CNS infection suspected Ix: LP if no contra-indication (*) and intracranial SOL/ swelling/ brain shift excluded by CT scan (**): -opening pressure -Gluc (paired with blood gluc)& protein -G stain, RM (+/- AFB smear) ,culture (+/-TB ) -viral PCR( HSV, VZV,enterovirus, +/-TB) (beware of false –ve CSF HSV PCR within first 3D of illness) -viral culture,bacterial culture, +/- TB culture -IgM and IgG for virus , mycoplasma -lactate -+/- oligoclonal band (paired with serum if suspected non-infectious related encephalitis) -spare specimens ( 3 bottles) to be kept in fridge NPAx resp virus, mycoplasma PCR Urine x pneumococcal Ag throat and rectal swab x enterovirus Blood x serology Vesicular fluid swab x VZV,HSV Empirical Tx ( Don’t delay if LP contra-indicated): Consider IV Cefotaxime + IV ampicillin (<3 mo), IV vancomycin (if suspect pneumococcus) IV Azithromycin (caution high macrolide resistant mycoplasma common) IV acyclovir : Neonate -3mo : 20mg/kg Q8h 3mo-12 yr :10-15 mg/kg Q8h 12-18 yr : 10 mg/kg Q8h Adjust dose in renal impairment Total 3 weeks (lower relapse rate if Tx high dose ≥30mg/kg/D and duration > 14D; otherwise relapse rate up to 26%) Consider oseltamivir 164 Section 4. Central nervous system If no obvious cause after initial assessment and initial Ix ( Unknown #) -CT scan -LP if safe -urine x toxicology screen -urine OA, AA -blood x AA, acylcarnitine -ESR/ AI screen ; TFT/ thyroid auto-antibodies -urgent EEG -Empirical treatment for CNS infection *Contra-indication for immediate LP : Features suggestive of raised ICP: -moderate to severe impaired conscious state (<13), or fall in GCS >2 -focal neurological signs (unequal/dilated or poorly responsive pupils) -abn posture or posturing -papilloedema -bradycardia (HR<60/min) -Hypertension ( BP>95% for age) -abnormal doll’s eyes -abn breathing pattern -had seizure lasting >10 min and still has GCS ≤12 Systemic factors: -shock - Respiratory insufficiency -coagulation abnormalities ( e.g. platelet <100 x109/L, abn clotting profile, if on warfarin, need to change to heparin first) -suspected meningococcal septicemia (extensive or spreading purpura) Local factors: -local infection at LP site ** A normal CT scan does not exclude acutely raised ICP 165 Section 4. Central nervous system Chapter 56 - EEG CS Ho Purpose: - Most commonly done for the diagnosis of seizure disorders - Certain manifestations such as impaired learning, strange behaviour or drop attack may be due to an underlying seizure disorder so EEG may sometimes be done - Certain neurodegenerative disorders - As an ancillary diagnosis of brain death Sedation for EEG: - Avoid using sedation as far as possible, refer to department sedation protocol - Even in small children, a quiet, comfortable and child-friendly environment may allow the child to go into natural sleep without using sedation - Sleep deprivation the previous night is useful both as an activation procedure to increase yield and to induce natural sleep during recording - Preferable to have recording in all stages from awake, drowsy to light and deep sleep. This is part of the reason why sedation is not preferred. Diagnosis: Significance - The diagnostic hallmark for epileptic disorders, the paroxysmal discharges (spikes), may be present in 3.5% of children with no clinical seizure manifestation. A small percentage (<10%) of these may subsequently develop clinical seizure in later life. - The EEG can be normal in half of the epileptic patients in the interictal stage. Patterns in epileptic disorders Interictal Findings Persistent burst suppression in neonates Hypsarrhythmia Generalized “slow” spike-waves Frequent / Continuous spike-waves during slow wave sleep Generalized 3/second spike-waves Epileptic Disorder Ohtahara Syndrome Infantile Spasm Lennox-Gastaut Landau-Kleffner CSWS Primary generalized epilepsy (If ictal absence epilepsy) Focal / Partial epilepsy Rolandic epilepsy → Focal spikes, sharp waves, spike-waves Centro-temporal spikes (increase during sleep) Other abnormalities: - Focal slowing: postictal change; mass lesion - Asymmetric background: congenital malformations; subdural effusion / haematoma; postoperative changes - Excessive generalized beta waves: drug effect; mental retardation EEG in the newborn: - Individual sharp waves difficult to interpret in newborns – may be normal in premature neonates. Only significant if frequent and persistently localized. - The background pattern is more important. Even in the quiet sleep stage the background should be bilaterally synchronous after 40 weeks gestational age and continuous by 44 weeks gestational age. A grossly suppressed background or a discontinuous background indicates serious underlying illness and/or bad prognosis. 166 Section 4. Central nervous system Chapter 57 - Sedation DK Ng, CS Ho Classification of physical status (American Society of Anesthesiologists) 1) A normal healthy patient 2) A patient with mild systemic disease (e.g. asthma with mild wheeze) 3) A patient with severe systemic disease (e.g. asthma with active wheeze) 4) A patient with severe systemic disease that is a constant threat to life (e.g. status asthmaticus) 5) A moribund patient who is not expected to survive without the operation (e.g. cardiomyopathy awaiting heart transplant) 6) For organ donor Four stages of Depth of Sedation: 1) Minimal Sedation / Analgesia (Anxiolysis) A drug-induced state during which patients respond normally to verbal commands. Cognitive function and cooperation may be impaired, ventilatory and cardiovascular functions are unaffected. 2) Moderate Sedation / Analgesia (Conscious Sedation) A drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. Spontaenous ventilation is adequate. Cardiovascular function is usually maintained. 3) Deep Sedation A drug-induced depression of consciousness. Patients cannot be easily aroused but respond purposefully following repeated or painful stimulation. Reflex withdrawal is not considered a purposeful response. The ability to maintain ventilatory function may be impaired; may require assistance in maintaining a patent airway; spontaneous ventilation may be inadequate. Cardiovascular function is usually impaired. 4) Anaesthesia A drug-induced loss of consciousness during which patients are not arousable, even by painful stimulation. Ability to independently maintain ventilatory function is often impaired. Patients often require assistance in maintaining a patent airway or drug-induced depression of neuromuscular function. Cardiovascular function may be impaired. Pre-sedation steps: 1. Monitoring of vital signs +/- SpO2 is essential during and after sedation 2. Appropriate sized mask and bag, oxygen and suction must be available at the bedside for immediate use. 3. All patients who will be given sedatives (including syrup chloral hydrate) for elective investigations / procedures should be put on NPO for at least 4 hours beforehand, to minimize the risk of vomiting / aspiration. 167 Section 4. Central nervous system Cautions: 1. Sedation must not be given to calm an irritable child when the underlying reasons, e.g. hypoxaemia, hypercapnia, cerebral hypoperfusion, are not clear. 2. When sedation is given to a child with borderline organ perfusion, a large patent IV access must be ensured beforehand and a bottle of normal saline must be immediately available. Medications: All intravenous sedatives must be titrated against the patient’s response. The initial calculated dose should be given in a stepwise fashion instead of one go. 1) Give melatonin 0.25-0.5 mg per kg (to be rounded up to no decimal place, up to 3 mg max.) 45 minutes before scheduled procedure. Keep the child on the stretcher in a quiet and darkened room to facilitate sleep and accompanied by parents 2) Chloral hydrate (A) Usual paediatric patient Initial dose: 50-75 mg/kg 2nd dose if first dose cannot adequately sedate patient in 30 minutes.: 25 mg/kg Cumulative dose should not exceed 2 gram (B) Reduce dosage Neonates: 50 mg/kg Patients with suspected ↑ intracranial pressure, respiratory depression, impaired liver / renal function: 25-50 mg/kg Give one dose only N.B. (a) Chloral hydrate should not be given in patients with liver / renal failure or in patients with gastritis (b) Syrup chloral hydrate has to be diluted before administration 3) Dormicum up to 0.1 mg/kg ivi 4) Fentanyl 1-3 mcg/kg ivi 5) Ketamine 1 mg/kg ivi, or 2 mg/kg imi (give atropine 0.01 mg/kg, minimum 0.1 mg before ketamine to decrease risk of laryngeal spasm) 6) Propofol 2.5-3.5 mg/kg (Caution : hypotension is common and is to be treated with iv fluid bolus + iv ephedrine) 168 Section 4. Central nervous system Chapter 58 - Normal neuro-developmental milestones MS Choi 1. Gross motor: 1 month: 3 months: 4 months: 5 months: 6 months: 7 months: 11 months: 12 months: 15 months: 18 months: 2 years: 3 years: 4 years: 5 years: 2. Fine motor: 1 month: 3 months: 4 months: 5 months: 6 months: 9 months: 12-15 months: 15 months: 18 months: 2 years: 2.5 years: 3-4 years: 5 years: Almost complete head lag when pulled to sit Complete flexed on ventral suspension Only moderate head lag when pulled to sit Extend head above plane of body on ventral suspension No head lag Draw feet to mouth and play with feet Roll over from prone to supine Sit with hands forward for support Bear weight when supported Sit without support Roll over from supine to prone Pivoting Walk while holding on furniture Crawl like a bear Stand up without help Sit in a chair Walk with mature gait Climb up and down stairs two feet per step Climb up stairs one foot per step Stand on one leg Hop on one foot Climb down stairs one foot per step Skip on both feet Fisting of hands Hands open Outreaching Hold on milk bottle Transfer Mouthing Finger-thumb grasp Throw objects Feed self with spoon Turn 2-3 pages of a book Turn single page Thread beads Fasten buttons Tie shoe lace 169 Section 4. Central nervous system 2.1. Drawings: 18 months: 2 years: 3 years: 4 years: 4.5 years: 5 years: From 3 years: Scribble Imitate circular scribble Copy a circle Copy a cross Copy a square Copy a triangle Draw a man (for every additional part of body, add 0.25 years) 2.2. Handedness: 1 year: 2-6 years: Shift from side to side Definite hand dominant 2.3. Cubes: 15 months: 18 months: 2 years: 2.5 years: 3 years: 4 years: 3. Speech: 3 months: 6 months: 8 months: 1 year: 15 months: 18 months: 2 years: 2.5 years: 3 years: 4 years: Tower of 2 Tower of 3 Tower of 6 Imitate train Tower of 8 Imitate train with chimney Tower of 9 Imitate bridge of 3 Imitate gate of 5 Cooing Babbling Respond to his name Respond to ‘NO’ Understand people’s name Use 2-6 recognizable words Use 6-20 words Point to 3-4 body parts Use 2-3 words simple sentence Give first name Give full name Full sentence of 4-5 words Give full name and sex Count 1-10 Give full name, age, sex and address Name primary colours 170 Section 4. Central nervous system 4. Hearing: 3 months: 6 months: 9 months: 5. Vision: 1 month: 3 months: 6-9 months: 6. Social: 1.5 months: 3 months: 6 months: 1 year: 2 years: 3 years: 4 years: Turns head to the direction of nearby noise or meaningful sounds Localize sounds at 18 inches on ear level Localize sound at 3 feet above or below ear level Follow objects to midline Follow objects beyond midline Fixate on hundreds and thousands at 12-15 inches Fixate and follow small object at 3 meters distance Graded ball vision tests usually applicable Social smile Interest in surroundings Stranger anxiety Kiss on request Wave ‘bye-bye’ ‘Parallel play’ Dry by day Join and play with other children Dry by night with occasional wet bed up to 4-5 years old Go to toilet alone 171 Section 4. Central nervous system Chapter 59 - Childhood epilepsy natural history (counselling) KK Chan, S Cherk Risk of seizure (Sz) recurrence: - 2nd sz after first sz ~40% (Berg & Shinnar) - 3rd sz after 2nd sz (less info) at least 80% (Camfield, Shinnar) - Predictor for 2nd sz: - remote symptomatic cause - partial sz - intellectual or mental handicap - EEG spikes - prior acute sz including febrile sz - status epilepticus - multiple sz at the index episode - Todd’s paralysis e.g. recurrence risk 20-30% in a normal child with GTC + normal intelligence and normal EEG vs 80-90% mental handicap + partial sz + spike discharge EEG Starting medication - no evidence prescription of medications alters long term prognosis of childhood epilepsy (Camfield 1996) - medications are anti-seizure rather than anti-epileptogenic (Kwan, Sander) - main reason to treat with medications: avoidance of bodily harm from sz and improvement in psychosocial function - only 20% will have “smooth-sailing epilepsy”, i.e. sz free immediately + later able to wean off AEDs without ever recurrence - only 50% children continue to receive the same medication 1 year after starting medication Long term remission - for many children, sz is transient and seems to vanish as the child gets older - at time of diagnosis: possible to predict at least 50% children will outgrow the disorder and be able to discontinue AEDs - the longer the follow-up period, the higher rate of remission - good prognostic factors: normal intelligence, normal physical examination, relatively small number of sz at diagnosis, age of onset younger than 12 years, absence of a remotely symptomatic cause, generalized onset of sz - good prognosis: 80% chance remission vs 40% in those with ≥ 1 adverse factor 172 Section 4. Central nervous system Stopping medications - ~70% children with epilepsy who have been sz free for 1-2 years can successfully stop AED (rate of success is not greater if medication is continued for up to 5 years) - Factors for successful discontinuation of AED: - generalized sz - age of onset < 10-12 years - normal neurological findings - resolution of interictal EEG spikes (some studies) - Children who have no adverse factors may have 80-90% success rate - Additive effect on adverse factors: those with all adverse factors have only 10-20% success rate - If initial discontinuation trial unsuccessful: re-start anticonvulsant previously on ~ 50% will become sz free again for sufficient time to try discontinuation of medications for 2nd time - 70 % success rate Ref: Swainman et al, Principle in Paed Neurol 2006 Kevin Farrell, E Wirrell. Definition & Prediction of Intractable Epilepsy in Children 173 Section 4. Central nervous system Chapter 60 - Therapeutic hypothermia in paediatric patients (excluding neonates) S Cherk Indication: Coma in patients who respond to resuscitation from cardiac arrest Aim: - Start cooling as soon as possible; can be started even up to 8 hours post arrest - Aim at target core temperature 32-34°C (avoid over-cooling and excessive fluctuation) - Cool to reach target as fast as possible e.g. 3-4 hours - Hypothermic duration 12-24 hours - Slow controlled re-warming at 0.25-0.5°C/hour to target 36°C Patient Preparation: - DO NOT actively re-warm patients who are spontaneously hypothermic - Inspect whole body for potential pressure sores. Need meticulous skin care. - Set arterial BP monitor (more difficult with subsequent vasoconstriction) - Prevention and control of shivering important: - Consider IV pethidine which increases threshold of shivering + prn neuromuscular blocker Method: - BLANKETEROLL II cooling blanket (adult / child / infant size +/- ice packs) - Preferably patient is sandwiched between 2 blankets (if not, patient covered by 1 cooling blanket) - Bed sheet between patient and cooling blanket - Meticulous nursing care (see Nurses’ protocol) Monitor: - Continuous core temperature monitor e.g. oesophageal temp - Secondary temperature device (core temp probe preferred) e.g. rectal / (skin temp) - Continuous BP monitor, maintain arterial BP - Watch hypotension especially during induction (diuresis) and re-warming (vasodilatation) - Continuous cardiac and SaO2 monitor - Watch for arrhythmia - Bradycardia often occurs: continue hypothermia if no haemodynamic problems - If ICP monitor present, maintain cerebral perfusion pressure > 55 mmHg (mean arterial BP - ICP) - blood tests - At 0 hour: CBC / clotting / RFT / PO4 / glu / arterial blood gases / troponin - Q6H: glu / K / ABG Watch hypoK during hypothermia; treat when K<3.5 Watch hyperK during re-warming Stop K administration once re-warming starts Need tight control of blood glucose (avoid hyperglycaemia – deleterious to injured brain) -Q12H: clotting / CBP Q12H (clotting may be falsely normal, as test is done at room temp) -Skin care Q2-6H for thermal injury -Watch for bleeding / abnormal clotting tendency 174 Section 4. Central nervous system Adverse reactions to watch out for: Arrhythmia Hypotension Initial decreased urine output Shivering – increased acidosis, decreased efficiency of hypothermia Prolonged half-life of drugs Electrolyte – K/PO4 Hyperglycaemia Abnormal acid base Decreased and impaired platelet count / function; bleeding tendency Increased risk of infection Discontinue active cooling and start re-warming if: - Life-threatening arrhythmia - Haemodynamic instability - Bleeding due to clotting dysfunction Re-warmimg (most critical) - Start 12-24 hours from initiation of hypothermia - Watch BP closely – high risk of hypotension as vasculature dilates (may need IV bolus if BP drops) - Watch hyperK- stop K infusion if any - Re-warm slowly at 0.25-0.5°C/hour to target 36°C (takes approximately 8 hours) - Maintain paralytic agent and sedation until temp ≥ 35°C - Check electrolytes (especially serum K) at start of re-warming and q4H until re-warming complete Others - No nutrition during whole period of hypothermia and re-warming - Don’t forget other neuro-protective measures e.g. head central and up 30° normocarbia 175 Section 4. Central nervous system Chapter 61 - Tics and Tourette’s syndrome in childhood TH Fung, S Cherk Tics- sudden, stereotyped, coordinated and involuntary movements or sounds Simple: single movement e.g. eye blinking Motor Complex: sequential pattern or coordinated actions Tics Vocal Simple: inarticulate noises or sounds Complex: partial words, words or phrases Features: - premonitory urge or sensation that improves after performing the movement - may be suppressible for a brief period of time - can lead to pain, injury - does not occur in sleep - onset < 18 years of age - not due to direct effects of drug / general medical condition - occur many times a day nearly every day Classification: DSM IV – TR: Type Transient tic disorder Chronic motor or chronic vocal tic disorder Tourette’s syndrome / disorder (TS) Features - at least > 4 weeks but < 12 months - either single or multiple motor and / or vocal tics - at least 1 year duration with no tic free period of > 3 consecutive months - single or multiple tics but confined to one class (either motor or vocal) - combination of motor and vocal tics (not necessarily at the same time) - at least 1 year duration with no tic free period > 4 consecutive months Evaluation - To distinguish from other type of involuntary movments: myoclonic jerks, stereotypies, dystonia and compulsions - Need to exclude: underlying organic cause e.g. CNS disorder, drug effect etc - Thorough history and neurologic examination generally sufficient - Imaging and EEG usually not needed - Check for - associated neuropsychiatric disorders like ADHD, OCD, mood disorders - psychosocial stressors - To determine which symptoms are disabling (target symptoms for treatment) Epidemiology - Chronic tic disorders: ~ 2-5% school-age children - Transient tic disorders at least as common as chronic tics - TS: ~10-30 cases per 10,000 children - M : F = from 10 : 1 to 2 : 1 - Peaks between 7 and 15 years - In TS, high co-morbidity rate of attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD) 176 Section 4. Central nervous system Prognosis and treatment - Natural history: symptoms wax and wane - 1/3 complete remission in late adolescence or young adulthood - Further 1/3 improves to mild severity A) Most need parental education and reassurance only B) Refer Clinical Pyschologist for behavioural therapy and look for co-morbid conditions e.g. Habit Reversal Therapy: application competing response whenever the patient notices tic or has urge to tic C) Refer Child Psychiatrist if Tourette Syndrome D) Treatment directed first at the most troublesome symptoms E) Medications (last resort): suppresses tics; choice depends on presence of co-morbidity: i) Clonidine: - first line in mild to moderate tics: 0.05 mg bd, gradually↑to 0.1mg bd / qid - if also ADHD: may be additive effect with Methylphenidate ii) neuroleptics a) fluphenazine, haloperidol, pimozide: tics decrease by 50-80%, but extrapyramidal side effects / tardive dyskinesia b) risperidone: fewer side effects E) Treatment co-morbid conditions e.g. OCD and ADHD 177 Section 4. Central nervous system Chapter 62 – Global developmental delay/ Intellectual Disability (Mental retardation) – diagnostic approach S Cherk Definition: Global developmental delay (GDD) = significant delay in ≧ 2 domains in children < 5 years: - GM + FM; Speech and language; Cognition; Personal and social; ADL - Significant = performance ≧ 2 SD below mean Intellectual Disability (ID) = significant sub-average intellectual ability accompanied by significant limitation in adaptive functioning - GDD is not always predictive of ID (environmental factors), but many cases will Classification of intellectual disability DQ level Mild intellectual disability 50-55 to approximately 70 Moderate intellectual disability 35-40 to 50-55 Severe intellectual disability 20-25 to 35-40 Profound intellectual disability 20-25 (Developmental Quotient (DQ): functional age/ chronological age ) Aetiology: - Estimate of diagnostic yield of GDD 10-81% (yield higher if moderate/ severe ID) - Commonest: - Genetic - Syndromal - Structural brain abnormalities - Genetic cause, test by - G-banded karyotype -> 4% (mild-mod ID: 3.7-10%) - FISH/ MPLA – 3.5% - Microarray – 7.8% - X-linked ID genes in male with appropriate F/H – up to 42% - IEM only found in 1-5% cases Diagnostic approach: History - Maternal history-e.g. recurrent spontaneous miscarriages suggests chromosomal rearrangement/ unbalanced translocation; - Previous stillbirths /neonatal deaths/ sudden infant death may underlie an IEM problem; - Exposure to potential teratogens, for example anti-epileptics, antidepressants, warfarin, alcohol (e.g. binge drinking in the first trimester), nicotine and illicit drugs; - Early neonatal events: complications of delivery, hypotonia, hypoglycaemia/seizures; - Family history - parental consanguinity (3 generation pedigree) (genetic syndrome ; neurological disorders /learning/ developmental problems) - Sleep disturbance / nocturnal snoring - Diet and pica - General medical history - Delay static or progressive/regression - Autistic features - Seizures 178 Section 4. Central nervous system - Hearing/ visual problem/eyes (+/- ophthalmological referral) Repetitive stereotypic hand movements (e.g. Rett, Happy puppet) Clinical examination - Growth parameters - Neurocutaneous stigmata - Dysmorphism, congenital abnormalities and reduced family resemblance - Features of storage disorders, –e.g. hepatosplenomegaly, corneal clouding - Cardiomyopathy –e.g. mitochondrial respiratory chain disorders - Visual impairment –e.g. retinitis pigmentosa and ciliary disorder - Neurological signs - Vision and hearing Diagnostic approach - Features syndromic or non-syndromic ? - refer for formal developmental assessment /Formal hearing assessment / formal vision assessment Need review regularly for regression or emergence of suggestive phenotype 179 Section 4. Central nervous system Investigations 1. 2. Thorough history and PE If diagnosis not apparent consider following investigations: First line investigations Full blood count Vitamin B12 /Ferritin Urea and electrolytes ,CPK, Lead Thyroid function tests (TT4/T3/TSH) Urine metabolic screen (including amino acid, organic acid, sugar chromatography & glycosaminoglycans (GAG) screen ) Refer Clinical Genetics (e.g. Molecular karyotype/ array CGH/XL DNA) Second line Consider discuss with or referral to neurologist or metabolic person or further discussion with geneticist for further investigations which may include: Metabolic Family history, consanguinity developmental regression, acute/ recurrent encephalopathy Recurrent vomiting Organomegaly, coarse features, hypotonia, myopathy Neuroimaging Abnormal head size seizures, focal neurological sign EEG Speech regression Seizures neurodegenerative disorder Genetics Dysmorphism abnormal growth sensory impairment, odd behavior, family history consanguinity Consider 24-h EEG MRI/ MRS CT (bones, calcification) Blood NH3, uric acid transferrin isoforms VLCFA, homocysteine paired blood and CSF lactate, pyruvate, glucose and amino acids +/- CSF neurotransmitters Urine EMU uric acid/creatinine Urine x homocysteine Consider : Urine & serum creatine and guanidinoacetate Priority in Ix: look for potentially treatable disorders Further tailored investigation depends on associated findings Repeated evaluation important as symptoms and signs may evolve 180 Consider skeletal survey Specialized genetic diagnostic testing Section 4. Central nervous system Table I History suggestive of IEM Features sugg of IEM Pregnancy HELLP, AFLP Family history Consanguinity, unexplained neonatal or infantile deaths X-linked inheritance pattern : Past medical history Type of developmental delay Other problems Unexplained hypoglycaemia Encephalopathy Protein aversion Self injurious behaviour Psychotic symptoms Regression/ progressive developmental delay Hypotonia Sensorineural deafness Seizures - Severe sz + Neonatal onset - Severe seizure infantile onset Seizures + extrapyramidal movement + hypotonia Progressive Neurological Symptoms Examples of IEM FAO -Creatine transporter deficiency -MCT8 mutations -Occipital Horn syndrome Urea cycle disorder Lesch-Nyhan, hyper-ammonaemia, purine/pyrimidine metabolism Cobalamin disorder, LSD, Wilson’s Strongly suggestive of IEM (+ severe sz: LSD) OA, FAO, urea cycle disorder Mitochondrial disease - NKH, perioxisomal disorders - Sulphite/ molybdenum cofactor deficiency - Glut Transporter Deficiency AA, CDG, Glycogen synthetase def, LSD, Menkes’ Dis, Mitochondrial dis, purine/ pyrimidine metabolism Creatine deficiency purine/ pyrimidine metabolism Neurotransmitter disease e.g. Biotinidose deficiency, purine/ pyrimidine metabolism, perioxisomal dis, folic metabolism HELLP – haemolysis elevated LFT & low platelet; AFLP – acute fatty liver pregnancy; FAO – fatty acid oxidation; LSD – lysosomal storage dis; OA – organic aciduria; AA – amino-acidopathy ; NKH – non-ketotic hyperglycinemia; CDG- congenital glycosylation defect 181 Section 4. Central nervous system Table II Examples Physical Findings suggestive of IEM or other underlying causes Feature Examples of Disorders Dysmorphism Cytogentic disease; syndromal diagnosis; CDG Hepato(spleno)megaly LSD, GSD Cardiomyopathy LSD, FAO, mitochondrial disease Smell OA (sweet – maple syrup urine disease; sweaty feet – isovaleric aciduria) Neurological signs: - dystonia Mitochondrial disease, OA, Pterin defects - macrocephaly Canavan disease, L-2-hydroxyglutaric aciduria, Glutaric aciduria I - microcephaly Sulfite oxidase deficiency, previous metabolic encephalopathy e.g. previous hyperammonemia/ hypoglycaemia, GLUT-1 deficiency, neuronal ceroid lipofuscinosis Growth Many IEMs e.g. OA, AA, urea cycle disorder (FIT, short stature) Hair – coarse, “kinky” Menkes disease, MPS, arginosuccinic aciduria Coarse skin, hair or Lad, Conradi-Hunermann facial features Ichthyosis Sjogren-Larsson Eczema Biotinidase deficiency Always consider possibility of a treatable disorder: - ↑T3, low N /↓T4 , N TSH ( Thyroid hormone transporter gene MCT8 mutation) - PKU (Pl AA) - Homocystinuria (plasma AA,↑blood total homocysteine) - Late-onset UCD (↑pl NH3, Pl AA) - Occipital Horn Syndrome (↓se Cu & ceruloplasmin) - Hartnup disease (neutral amino-aciduria) - Cerebrotendinous xanthomatosis (fasting↑pl cholestanol , n/↑cholesterol) Other second line investigations that may be considered: - Glycosaminoglycans – coarse facial dysmorphism may be absent in MPS III - VLCFA – progressive encephalopathy with mental deterioration - Iso-form transferrin – CDG: suspect in all unexplained encephalopathy (+ abnormal fat subcutaneous accumulation, cerebellar atrophy) or multi-organ disorders (heart, liver, kidney, GI tract, skeletal, gonads, coagulation defects causing stroke-like episodes) - Paired CSF / serum glycine – NKH (infantile onset severe seizures) - Paired CSF / serum glucose – Glut Transporter deficiency (infantile onset severe seizures) - Plasma homocysteine – Sulphur AA disorder (progressive dev delay) - Fresh urine x sulfite – sulphite delay oxidase / molybdenum co-factor deficiency (infantile encephalopathy, progressive dev delay, severe microcephaly, lens dislocation) Example of disorders according to investigations: - Ca: Williams syndrome, Di-George Syndrome, pseudo-hypoparathyroidism - Lactate: screening for gluconeogenesis, disorders of pyruvate metabolism; respiratory chain mitochondrial disease - NH3: urea cycle problem; AA - Amino acid chromatography: AA - Urine OA: OA and some FAO - CK: FAO (non-specific), muscle disorders - Urate: ↓ in purine metabolism; molybdenum cofactor deficiency; ↑ in Lesch-Nyhan, glycogen storage disorders 182 Section 4. Central nervous system Chapter 63 - Anti-convulsants use in children with epilepsy TH Fung, S Cherk, CL Yuen Table 1. Choice of AED in different situation Seizure (Sz) 1st line drugs 2nd line drugs types Focal seizure +/- ※Carbamazepine ※Oxycarbazepine secondary ⊕Levetiracetam GTCSs Topiramate ※Lamotrigine 1’ GTCSs only Myoclonic seizure only Absence seizure only Valproate ⊕Levetiracetam Topiramate ※Lamotrigine Valproate §Clonazepam ⊕Levetiracetam Valproate (ethosuximide) ※Lamotrigine §Clobazam Valproate Gabapentin 3rd line drugs Phenobarbital ※Phenytoin lacosamide Vigabatrin (zonisamide) ※Carbamazepine ※Oxycarbazepine ※Phenytoin (ethosuximide) Topiramate Valproate (ethosuximide) ※Lamotrigine Tonic or atonic seizures Valproate ※Lamotrigine Topiramate §Clonazepam §Clobazam Photosensitive or other reflex seizures Valproate ⊕Levetiracetam §Clonazepam §Clobazam §Clonazepam (zonisamide) §Clonazepam §Clobazam ⊕Levetiracetam Topiramate (zonisamide) (Rufinamide) ※Lamotrigine ※Na channel blocker- CBZ,OXC,LGT,PHT Multiple mechanisms, mainly or incl Na channel blocking- PB,VPA,TPM,Zonisamide § ↑GABA- benzodiazepines, VGB Synaptic SV2A-LVTM ⊕ Try to choose a drug with a difference mechanism in combination therapy 183 Drugs to be avoided ※Carbamazepine ※Oxycarbazepine ※Phenytoin Vigabatrin Gabapentin If also absence / myoclonic Sz ※Carbamazepine ※Oxycarbazepine ※Phenytoin Vigabatrin Gabapentin ※Carbamazepine ※Oxycarbazepine ※Phenytoin Vigabatrin Gabapentin ※Carbamazepine ※Oxycarbazepine Vigabatrin Gabapentin Section 4. Central nervous system Table 2 Drug options by epilepsy syndrome Epilepsy syndrome Childhood absence epilepsy Juvenile absence epilepsy Juvenile myoclonic epilepsy (ethosuximide) Lamotrigine Valproate ※ §Clobazam §Clonazepam ⊕Levetiracetam Topiramate ⊕Levetiracetam Focal epilepsies: cryptogenic, symptomatic ※Carbamazepine ※Lamotrigine ※Oxcarbazepine Benign epilepsy with occipital paroxysms Severe myoclonic epilepsy of infancy Continuous spike wave of slow sleep Lennox-Gastaut syndrome Myotonic astatic epilepsy Topiramate ※Lamotrigine Valproate Topiramate Valproate Topiramate Valproate Topiramate Steroids Vigabatrin ※Carbamazepine ※Lamotrigine ※Oxcarbazepine Valproate ※Carbamazepine ※Lamotrigine ※Oxcarbazepine Sodium valproate §Clobazam §Clonazepam Valproate Topiramate Clobazam Clonazepam (ethosuximide) Lamotrigine Valproate Steroids Lamotrigine Valproate Topiramate §Clobazam (Gabapentin) ⊕Levetiracetam ※Phenytoin §Clobazam §Clonazepam Valproate Topiramate Levetiracetam Topiramate ⊕ Acetazolamide Clobazam Clonazepam Oxcarbazepinea Phenobarbital Phenytoin (Primidone) Acetazolamide Clonazepam Phenobarbital (Primidone) § § ※ ※ ※Carbamazepine ※Oxcarbazepine ※Phenytoin Vigabatrin ※Carbamazepine ※Oxcarbazepine ※Phenytoin Vigabatrin ※Carbamazepine ※Oxcarbazepine ※Phenytoin Vigabatrin Vigabatrin § Nitrazepam ※Carbamazepine ※Oxcarbazepine (Sulthiame) Topiramate ⊕ Levetiracetam (Stiripentol) ⊕Levetiracetam ※ §Clobazam §Clonazepam (ethosuximide) ⊕Levetiracetam ※Lamotrigine ⊕Levetiracetam Valproate Topiramate Acetazolamide Drugs to be avoided ⊕Levetiracetam § § ※ §Clobazam §Clonazepam 3rd line drugs ⊕Levetiracetam ⊕Levetiracetam Valproate Generalised tonic– clonic seizures only Benign epilepsy with centrotemporal spikes 2nd line drugs ※Lamotrigine ※Carbamazepine ※Lamotrigine Infantile spasms ( 1st line drugs Phenobarbital Topiramate ※Carbamazepine ※Lamotrigine ※Oxcarbazepine Vigabatrin ※Carbamazepine ※Oxcarbazepine Vigabatrin ) drugs not available in HK 184 (Sulthiame) ※Carbamazepine ※Oxcarbazepine ※Carbamazepine ※Oxcarbazepine Section 4. Central nervous system Table 3. Commonly used AED and major side effects *Carbamazepine Drowsiness, rash, Steven Johnson syndrome (SJS), anticonvulsant hypersensitivity syndrome (AHS), hepatic failure, headache, hypoNa+, diplopia, ataxia, nystagmus, arrhythmia, tremor, hematological #Valproate Nausea, vomiting, weight gain, tremor, hair loss, hepatic failure, pancreatic failure, hormonal change in women Phenobarbitone Rash, SJS, severe drowsiness, impaired cognition and concentration, agitation /hyperactivity , hepatic failure,AHS, hematological, shoulder hand syndrome Phenytoin Rash, SJS, drowsiness, ataxia, gum hypertrophy, hirsutism, AHS, hepatic failure, hematological, encephalopathy, rickets, oxycarbazepine Rash, SJS, drowsiness, ataxia, diplopia, weakness, hematological ##Lamotrigine Rash, SJS, tics, ataxia, asthenia, insomnia, diplopia, dizziness, headache, hepatic failure, hematological, AHS ^Topiramate Anorexia, weight loss, drowsiness, renal stone, metabolic acidosis, impaired concentration/ memory, psychomotor slowing, nervousness, acute glaucoma, hepatic failure, anhidrosis Irritability, behavioral changes, asthenia, dizziness ♣Levetiracetam - *Carbamazepine – check HLA B *1502 first - #Use of VPA unsuitable in children who are at considerably risk of fatal hepatoxicity (e.g. young children esp. <2yrs old, those with polypharmacy or with congenital metabolic disorders or organic brain disease) Warning signs of hepatic failure: clinical and non-specific e.g. malaise, weakness, lethargy, facial edema, anorexia, vomit and loss of seizure control. Risk 1/600 in <3yr, 1/8000-1/10,000 in 3-20yr - AHS – Anticonvulsant hypersensitivity syndrome: rash, fever, tender lymphadenopathy, hepatitis or eosinophilia; potentially fatal; usually cross sensitivity between AEDs that can cause AHS - #caution in female – VPA in pregnancies→1-2%with neural tube defects, 2-3x higher major congenital anomalies, probably associated with poor cognitive outcome in offsprings Switch valproate to other less teratogenic drugs in childbearing age female well before pregnancy - ##lamotrigine – dose in combination with VPA needed to be halved - ^topiramate – special precaution in those predisposed to acidosis (eg renal disease, ketogenic diet) or renal stone formation ( family history, hypercalciuria); Avoid therapy predispose to heat related disorders (other carbonic anhydrase inhibitor, anticholinergic drugs) - ♣levetiracetam – likely the AED most free from side effects 185 Section 4. Central nervous system Chapter 64 - Migraine CL Yuen, S Cherk Migraine without aura (ICHD-II) Diagnostic criteria A At least five attacks fulfilling criteria B–D B Headache attacks lasting 4–72 h (including the time when patients fall asleep till awakening) C Headache has at least two of the following characteristics: 1 Unilateral location (commonly bilateral in young children) 2 Pulsating quality 3 Moderate or severe pain intensity 4 Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs) D During headache at least one of the following: 1 Nausea and/or vomiting 2 Photophobia and phonophobia E Not attributed to another disorder Migraine with aura Diagnostic criteria A At least two attacks fulfilling criteria B–D B Aura consisting of at least one of the following, but no motor weakness: 1 Fully reversible visual symptoms including positive features (e.g. flickering lights, spots or lines) and/or negative features (i.e., loss of vision) 2 Fully reversible sensory symptoms including positive features (i.e. pins and needles) and/or negative features (i.e., numbness) 3 Fully reversible dysphasic speech disturbance C At least two of the following: 1 Homonymous visual symptoms and/or unilateral sensory symptoms 2 At least one aura symptom develops gradually over ≥5 min and/or different aura symptoms occur in succession over ≥5 min 3 Each symptom lasts ≥5 min and ≤60 min D Headache fulfilling criteria B–D for Migraine without aura begins during the aura or follows within 60 min E Not attributed to another disorder Features of aura in migraine Visual and/or sensory and/or speech symptoms. Gradual development, duration ≤1 h, a mix of positive and negative features, and complete reversibility Acute drug treatments - to be given at onset of attacks Panadol 15mg/Kg/dose (max dose at 1000 mg) (repeat in 4 hours PRN, max 3 doses in 24 hours) NSAID e.g. Ibuprofen 10mg/Kg/dose (repeat in 4 to 6 hours PRN, max 4 doses in 24 hours) Zolmitriptan 2.5mg (repeat in 2 hours PRN; max 15mg in 24 hours) 186 Section 4. Central nervous system Preventive drug treatments - no well established effective treatments in paediatrics Flunarizine 5-10mg Daily Cyproheptadine 0.1-0.2mg/Kg/dose BD dose (max daily dose: 0.5mg/Kg/day) Propranolol 0.2-0.5mg/Kg/dose TDS dose (max dose 4mg/Kg/day) Others: topiramate and valproate Behavioural therapy Life style and diet modification: balanced and healthy diet without skipping meals, adequate hydration, avoid caffeine, regular exercise and sufficient sleep Headache diary and headache education leaflet (available from Neurology Section of Department web page) 187 Section 4. Central nervous system 188 Section 4. Central nervous system Chapter 65 - Neonatal seizure TH Fung, S Cherk, CL Yuen Acute Neonatal seizure management Is it a seizure ? Vs other movements: jitteriness, benign sleep myoclonus, reflex behaviors etc Yes seizure characterize the seizure ABC Start oxygen if seizures are continuous IV access baseline investigations including CBP d/c, RLFT, glu, Ca2+, Mg+, Na+, K+ , blood gas, infective screen, TFT, uric acid, ammonia, lactate, urine ketones brain imaging – urgent CT brain To NICU/ PICU Follow this pathway if seizure ongoing > 3mins or seizure impairing vital functions Phenobarbitone 20mg/kg iv loading over 20mins If no response by 10mins Further 10mg/kg iv x once or twice until seizure cessation orl total 40mg/kg phenobarbitone given If no response by 10mins Phenytoin 10mg -20mg/kg iv over 20mins If no response by 10mins Phenytoin 10mg/kg iv further ( + PR paraldehyde 0.1ml per dose) If no response by 10mins Lorazepam 0.05mg/kg iv q6-8hr Or midazolam 0.15 -0.5mg/kg/hr for full term 189 Section 4. Central nervous system If still seizure Pyridoxine 100mg iv stat (best under EEG; cardiopulmonary monitor and resuscitation standby for possible apnea or cardiorespiratory collapse) If response Pyridoxine maintenance: -5-15mg/kg/day po in 2 divided doses if no response Other AED -Iv Levetiracetam ( status: 20-30mg/kg iv loading over 15mins, then 10m/kg/day ÷2, ↑by 10mg/kg/day over 3days to 30mg/kg/day-> may up to 45-50mg/kg/day) -Iv lidocaine (2mg/kg iv over 10mins followed immediately 6mg/kg/hr x 6hrs-> 4mg/kg/hr x 12hrs->2mg/kg/hr x 12hrs) -Iv valproate (status: 20-40mg/kg over 15mins then 5mg/kg/hr) plus -Pyridoxal-5-phosphate (PLP) po 30-50mg/kg/day in 3 divided doses -Folinic acid po 3-5mg/kg/day -biotin po 5-20mg/day For frequent but brief seizures shorter than 3mins each, anticonvulsant(AED) treatment is still warranted for seizure attacks abortion. The sequence of medication choice generally follows the above but the timing of escalation of AED treatment can be variable and individualized depending on the underlying causes, seizure types, seizure frequencies, systemic stability and need to balance with side effects of AED. Neonatal seizure: to differentiate from other paroxysmal movements that are not seizures : Jitteriness – involuntary rhythmical rapid alternating contractions of agonist and antagonist muscles, 4-5Hz, equal intensity; mainly limbs, can be asymmetrical Benign sleep myoclonus – during NREM sleep, myoclonic movements in an otherwise normal neonate, usu over distal parts of ULs but also LLs and axial muscles, can be violent, last usu for 10-20s but may up to 30mins in unusual cases Other reflex behaviors – eg exaggerated startle Generally seizures are not suppressible by passive restraints over the “ seizing” joints 190 Section 4. Central nervous system Types and characteristics : -Subtle seizures (50%) (imitate normal behavior; ocular, oral-buccal-lingual, progression movement, complex purposeless movement) -Tonic seizure (5%) -Clonic seizure (25%) -Myoclonic seizure (20%) -1/4: have multiple Sz types -Autonomic changes (HR, RR, BP, apnea (seldom alone), salivation, pupillary changes) -Subclinical seizure common; only ~20% of neonatal seizure had definite clinical signs -Clinical silent Sz are more common after initiation of AED - “ decoupling response” Causes: -Most are acute reactive Sz from acute encephalopathy:HIE ( most common cause,65%- 80%) metabolic (electrolyte, glucose) trauma/haemorrhage Infection drug (toxic/withdrawal) -Neurometabolic (IEM) -Cerebral malformation -benign neonatal convulsions (familial, non familial) Diagnoses: History : 1) seizure hx: seizure type, day of onset 2) antenatal hx: maternal illness, AN infection, AN drug use, abnormal AN fetal movement 3) perinatal hx: birth hx, NRFS, need resuscitation, apgar score, cord blood pH 4) feeding hx: is seizure onset related to feeding 5) family hx Baseline investigations: CBP d/c, RLFT, glu, Ca2+, Mg+, Na+, K+ , blood gas, infective screen, TFT, uric acid, ammonia, lactate, amino acid urine ketones Urine organic acid, metabolic screen CSF infective screen Neuroimaging: Urgent CT brain MRI brain in all cases EEG Urgent EEG Consider aEEG monitoring Further investigations if causes not elicited from above/ not typical for benign idiopathic neonatal seizure ( familial/non familial) / if clinical encephalopathic/ relative difficult to treat seizures: 191 Section 4. Central nervous system Blood – acylcarnitines, NH3, lactate, pyruvate, very long chain fatty acids, copper and ceruloplasmin Urine – organic acids, purines and pyrimidines + sulfites ( PMH urine metabolic screen), alpha AASA + guanidoacetate + creatine (available in QMH) CSF – glucose+ lactate + amino acids (these to be paired with serum sample); neurotransmitters + pipecolic acid (available in QMH) Consider Investigation for specific IEM if seizure resistant : - pyridoxine dependent epilepsy - pyridoxal-5-phosphate (PLP) dependent epilepsy - biotin responsive -> biotinidase def or holocarboxylase synthetase deficiency Duration of treatment: -Depends on cause, severity, recovery, neurological outcome, EEG abnormality -Current trend: to withdraw AED 2weeks after last Sz with normal EEG and good outcome predictors (clinical impression of benign neonatal convulsions, neuroimaging and neurological examinations normal) -practically, often re –evaluation in 1-2mths after discharge to discontinue AED Outcome: -28% death, 72% survivor -2yr follow up of 86% of survivors – 42% abnormal PE 55% MDI (mental developmental index) <80 50% PDI (physical developmental index) <80 26% epilepsy 192 Section 4. Central nervous system Chapter 66 – Screening/quick reference Cerebral Palsy LY Wong, S Cherk Definition: Permanent disorder of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances occurred in the developing fetal or infant brain. It is often accompanied by disturbances of sensation, perception, cognition, communication, behaviour, by epilepsy and by secondary musculoskeletal problems. Although the manifestations may change over time, the causative lesion is static. Overall prevalence remain unchanged at 2.11 per 1,000 live birth. Highest pooled prevalence in children weighing 1000 to 1499g at birth. Overall point prevalence 1.3 per 1000 children in Hong Kong. Clinical approach to patient with “Cerebral palsy” Family history Birth and past medical history: In general: preterm in symmetrical or asymmetrical spastic diplegia; full term in hemiparesis. History of term asphyxia in dyskinetic CP. Age of presentation Any unusual presentations/ mimics of cerebral palsy Hereditary spastic paraparesis- +ve Family history of “cerebral palsy” Dopa responsive dystonia- might have diurnal variation of symptoms Other inborn errors of metabolism-progressive signs and symptoms (regression), unusual associated problems e.g. hypoglycemia, recurrent vomiting, multi-organ involvement or progressive worsening seizures; FH of early death Idiopathic toe walking- Normal deep tendon reflexes Cerebral palsy “of unknown etiology”: be vigilant for the appearance of a late symptom that might suggest a more specific diagnosis International Classification of Function (ICF) Enablement framework in assessment and management of children with cerebral palsy Health Condition Cerebral Palsy Body Function and Structure Tone, Strength, Range Selectivity Activity GMFCS and gait GMFM Environmental Factor Accessibility Familial and Emotional Support Participation Involvement in Home, School and Community Events, Social relationship Personal Factor Age, Cognitive Function, Personality 193 Section 4. Central nervous system Assessment: Body Function and Structure • Tone: Measurement of Spasticity: Modified Ashworth Scale (Bohannon) 0= No ↑ in muscle tone 1= Slight ↑ in tone with a ‘catch and release’, or minimal resistance at end of ROM. 1+= Slight ↑ in tone, catch followed by a minimal resistance through <1/2 remainder of ROM 2= More marked ↑ in tone through most of the ROM, but limb moves easily 3= Considerable ↑ in tone, passive movement difficult 4= Affected part is rigid in flexion or extension Modified Tardieu Scale (Boyd 1998, 1999) Measurement of R1 and R2 : R2-R1 dynamic component R2 static contracture • • Assessment of Activity in Cerebral Palsy Gross Motor Function Classification System (GMFCS) Level 1 Walks without restrictions: limitations in more advanced gross motor skills. Level 2 Walks without assistive devices: limitations walking outdoors and in the community. Level 3 Walks with assistive mobility devices: l limitations walking outdoors and in the community. Level 4 Self mobility with limitations: children are transported or use power mobility outdoors and in the community. Level 5 Self mobility is severely limited even with the use of assistive technology. • • • Manual Ability Classification System(MACS) for upper limb Communication Function Classification System (CFCS) Gait analysis 194 Section 4. Central nervous system • Hip surveillance: (Part of assessment of body structure) Depends on GMFCS level GMFCS Level 1: low risk of hip displacement (Migration percentage >30% : Hip subluxation, >50% Hip dislocation) Migration percentage (MP) = A÷B x100% GMFCS GMFCS Level 1 GMFCS Level 2 GMFCS Level 3 GMFCS Level 4 GMFCS Level 5 Start of screening: 12-24 months Frequency thereafter Review with P/E at 3 year Every 12 mo till MP stable, then review at 4-5 years Every 12 mo if MP stable, 6 mo if MP unstable Same as level 3 but 6 monthly surveillance if with scoliosis or pelvic obliquity 6 monthly till 7 year End of surveillance Review with P/E at 5 year 8-10 year Yearly till skeletal maturity Yearly till skeletal maturity Yearly till skeletal maturity Interventions for children with cerebral palsy Conventional therapy Splinting, Casting Orthoses, Seating modification Stretching Tone Management Botulinum toxin type A Localization method: Ultrasound guided preferred Effect: Initial effect seen at 24-72 hrs Maximal effect 2-4 weeks Effect last for 4-6 months Best combined with casting Selective Dorsal Rhizotomy Reduce lower limb spasticity by removal of the excitatory influences from the dorsal roots Suitable candidates: Spastic, Straight, Strong, Smart, Slim, Support Usual treatment timeline: Between 5-8 years of age Intrathecal Baclofen Not readily available in Hong Kong Oral medications Might consider in whole body involvement Drugs: Diazepam, Baclofen, Dantrolene, Tizanidine Orthopedic Surgery Single Event Multi Level Surgery 195 Section 4. Central nervous system FU issues in Cerebral palsy 1) Medical co-morbidities -epilepsy, scoliosis, perineal care 2) visual/hearing impairment (VA; visual field defect in hemiplegic CP) 3) GIT- GERD, constipation (in low GMFCS level) 4) Swallowing problems, nutrition, dental care (especially in low GMFCS level) 5) bladder dysfunction (in spastic cerebral palsy) 6) Mobility and physical activity 7) Communication 8) Cognitive impairment/specific learning needsSelf Care 9) Self Direction (especially for those studying in mainstream school) Frequency of impairment in CP Impairment Motor Spasticity Dyskinesias Ataxia Isolated hypotonia GMFCS I II III IV V IQ <70 Ongoing epilepsy Visual impairment Blind Hearing impairment Deaf % of ALL CP Affected 100 77-93 2-15 2-8 0.7-2.6 32-51 17-21 9-12 10-15 12-19 17-60 31-40 21-63 1-7 11-13 1.7-3 Prediction for ambulation Ref : Developmental Medicine & Child Neurology 2009;51:295-302 196 Section 4. Central nervous system Chapter 67 – Screening/quick reference Special note on management of various types of cerebral palsy LY Wong, S Cherk Goal setting: short, intermediate and long term Structural and Activity assessment Treatment and Medications Orthosis Watch out for complications Spastic Diplegia Define functional level (GMFCS) Spastic Hemiparesis Define Upper limb functional level: MACS Spastic Quadriparesis General Health, Body structure nutrition and feeding Mobility and prevention of complications UL: Early Tx of spasticity Seating, mobility and communication needs Assess UL tx outcome by Goal Attainment Scale (GAS) Study gait + P/E to decide medical treatment Botox Consider SDR Orthorpaedic interventions at school age Depends on gait In general hinged AFO NOT recommended Hip surveillance based on GMFCS recommendation Medical complications Schooling Early consideration of AAC and AT (Assisted technology) Watch out for visual and hearing impairment Watch out for hearing loss if history of severe NNJ Botox To increase UL use by *CIMT or **BOT Oral medications might be tried Oral medications might be tried Might consider ITB if available Might consider hinged AFO UL functional splint To prevent complications and to aid training such as standing exercise Hip surveillance Watch out for scoliosis In general not recommended Look for sensory impairment ; visual field defect Watch out for epilepsy Watch out for word learning difficulties, visual perceptual problem and attention deficit especially those in normal school Education and social support Early plan for transition Vocational plan Social LL: Early treatment of spasticity Same as diplegia Dyskinetic CP Define functional level Communication Function Classification System (CFCS) Seating, mobility and communication needs Watch out for pain and discomfort Watch out for epilepsy Screen for osteoporosis /pathological fracture Nutritional need Maintain hydration and nutrition Family and social support +/-Home modification Early plan for long term care Family and social support Early plan for long term care Watch out for learning needs (usually attend normal school) Early plan for transition Vocational plan CIMT (Constraint Induced Movement therapy) ** BOT – Botulinum toxin * 197 Section 5. Gastroninterstional system Section 5: Gastrointestinal system 198 Section 5. Gastroninterstional system Chapter 68 - Acute Gastroenteritis PT Yu, L Leung, MC Chan Definition and Diagnosis - Sudden change in stool consistency to loose or watery stools, and/or a sudden onset of vomiting, +/ - fever. Diarrhea usually lasts 5-7 days (<2 weeks), vomiting 1-2 days (in most stop by 3 days) Possible indicators of diagnoses other than gastroenteritis: - Fever: >38°C in children <3 mo; 39°C in children aged 3 >/=3 mo - Shortness of breath or tachypnoea Altered conscious state Neck stiffness Bulging fontanelle in infants - Non-blanching rash - Blood and/or mucus in stool - Bilious (green) vomit - Severe or localised abdominal pain Abdominal distension or rebound tenderness. - - Clinical Feature That suggests Bacterial versus Viral Etiology High fever (>40°C), overt fecal blood, abdominal pain, CNS involvement Vomiting and respiratory symptoms are associated with a viral etiology - Investigations No routine blood test for children who are not septic, not dehydrated Na, K, Ur, Cr , glucose , blood gas for those with dehydration/ need IVF CBP with differential count, CRP only for suspected bacterial GE Blood culture only when started antibiotics Stool for culture should NOT be routinely performed - Indications for stool culture - Suspect septicaemia Septic or toxic looking Blood and/or mucus in stool diarrhea not improved by day 7 uncertainty about the diagnosis of GE - Immunocompromised patient recent travel history infants <3 months old specific pathogen community outbreak Assessing dehydration / shock The best measure is % body weight loss from recent (< 2 wks) weight. Clinical signs are imprecise. The 3 best signs are: prolonged capillary refill, reduced skin turgor and abnormal respiratory pattern. 199 Section 5. Gastroninterstional system Interpret symptoms and signs taking risk factors# for dehydration into account. Within the category of ‘clinical dehydration’ there is a spectrum of severity indicated by increasingly numerous and more pronounced symptoms and signs. For clinical shock, one or more of the symptoms and/or signs listed would be expected to be present. Dx of shock is based on clinician’s global assessment. Dashes (–) indicate that these clinical features do not specifically indicate shock. Symptoms and signs with red flags may help to identify children at increased risk of progression to shock. If in doubt, manage as if there are symptoms and/or signs with red flags. From NICE 2009 Clinical Dx dehydration shown to be imprecise. Presence Suspect hypernatraemic dehydration if of one or more symptoms or signs conventionally used in - Jittery movements assessment would suggest clinically significant - Increased muscle tone dehydration. ★ - Hyperreflexia Convulsions Drowsiness or coma. Risk Factors# for dehydration • • • • • • ★ ★ Red flag sign = alert clinician to risk of progression to shock Dx of shock based on physician’s global assessment. If unsure severe dehydration or early shock, treat as for shock. Infants, esp <6 months Infants who were of low birth weight Children who have passed ≥ 6 diarrhoeal stools or vomited ≥3x in last 24 hrs Children who have not had/ not tolerated supplementary fluids Infants who have stopped breastfeeding during the illness. Infants with signs of malnutrition 200 Section 5. Gastroninterstional system Management Oral rehydration therapy: (ORT first line always, unless indicated for IVF) • For clinical dehydration but no signs of shock: replace deficit 40-50ml/kg + maintenance fluids as low osmolality ORS over 3-6 hours frequently (longer duration for older children), in small amounts (eg by cup, syringe or teaspoons up to every 1-2 mins by parent). (Cincinnati: minimal amount is 240ml over 4 hrs for <5 yr olds and 480 ml over 4 hrs for ≥5 yr olds) • Always try ORT first (including in hyperNa and severe dehydration unless indications for IVF is seen), may set up IV access for patient admitted late in the evening in case of ORT failure and need IVF • When oral rehydration not feasible, NG rehydration is preferred and should be proposed before IV therapy. • Allow milk, breast milk and water during rehydration if they refuse ORS and have no red flag signs (but avoid carbonated drink, juice). • For ongoing loss: add 5ml/kg per large watery diarrhea (NICE). • Reassess frequently patients with red flag signs for any need of escalation of management. Write down alert criteria for nurses. Intravenous Fluid Therapy (IVT) indication - Suspected/ confirmed shock Dehydration with altered consciousness or severe acidosis. Patient with red flag signs shows clinical evidence of deterioration/ lack improvement despite ORT Persistently vomit ORS solution given orally or via a nasogastric tube Severe abdominal distension and ileus. Switch to oral rehydration as soon as indications for IV rehydration no longer seen. A. For Shock: arrange admission to PICU - Rapid infusion of 20ml/kg NS or Ringer’s lactate (esp. in extremely severe cases of shock) bolus, repeat 2nd bolus if BP has not improved, consider other causes of shock and PICU admission if not satisfactory after 2nd bolus. - After signs of shock resolve, start rehydration with IVT (see below). B. For cases with significant (moderate/ severe) dehydration without shock - Can replace deficit 40-50ml/kg isotonic solution (NS or Ringer’s lactate) over 2-4 hrs (NICE, ESPGHAN) on top of maintenance. - Regular reassessment to see if this reverses signs of clinical dehydration and guide ongoing fluid needs. 201 Section 5. Gastroninterstional system IV rehydration rate IV Rehydration has been traditionally over 24 hours, but latest guidelines (NICE, ESPGHAN, WHO) favour rapid replacement 20ml/kg/hr of NS for 2-4 hrs (in an otherwise well child with no hypernatraemia **) as this improves gut and renal perfusion, faster recovery and LOS. C. Subsequent fluid regime - Rapid rehydration is followed by: oral rehydration or continuous IV infusion of dextrose containing crystalloid solution once fluid volume is restored - For those who presented with shock: additional 100ml/kg for replacing deficit on top of maintenance, using NS or NS 5%D for deficit replacement and maintenance (NICE). For those without shock, as for B. - A solution containing not <0.45% saline is recommended during the first 24 hours of IV rehydration therapy to prevent hyponatremia (ESPHGAN). - Early start of ORT after 1-2 hrs of IVT. If tolerated, stop IVT and complete rehydration with ORT. - After child urinates or K+ come back low, may add KCl supplement 20mmol/L, or add oral K supplements. - Remember to add maintenance and continuing losses into fluid calculation and to reassess patient. - Restart ORS if dehydration recurs after rehydration. - Careful monitoring of electrolytes for those on IVT, alter fluid composition or rate of IVT as needed. **Hypernatremic dehydration (Na >145mmol/L) Oral or NG rehydration with hypoosmolar ORS is effective and safer treatment of hypernatremic dehydration than IV rehydration. If child needs IV rehydration: 1) use isotonic solution (N/S or N/S+5% D) for fluid deficit replacement and maintenance 2) replace deficit slowly (over 48 hours) esp in those with Na >160mmol/L 3) reduce Na level at a rate < 0.5 mmol/l per hour, slower if hypernatremia >5 days. Others Do not give antibiotics routinely. Give antibiotic treatment to children with: - Suspected septicaemia Salmonella GE in those< 3 months, malnourished or immunocompromised. Clostridium difficile (ie Pseudomembraneous enterocolitis), dysenteric shigellosis, dysenteric amoebiasis, cholera or giardiasis Antiemetics , anti-motility agents, prebiotics are not recommended. Probiotics (eg: Lactobacillus GG ) are effective in reducing the duration of diarrhea ( can be considered in cases with prolonged symptoms): dose of at least 10 billion CFU/day of LGG -for total 5 to 7 days Major references: NICE 2009, ESPGHAN 2014 guidelines. 202 Section 5. Gastroninterstional system Chapter 69 - Gastro-oesophageal reflux MC Chan Gastro-oesophageal reflux (GOR): retrograde flow of gastric content into oesophagus Gastro-oesophageal reflux disease (GORD): symptoms or complications of GOR Population at high risk for GERD and its complications: neurological impairment, obese, repaired esophageal atresia, hiatal hernia, achalasia, chronic respiratory disorders (e.g. BPD), history of lung transplant, preterm infants Evaluation: History and physical examination: - Identify pattern of vomiting, important to rule out bowel obstruction (bile stained vomitus, forceful vomiting), infection, metabolic diseases, food allergy, and neurological diseases - Pay attention to feeding volume and frequency, weight gain, irritability and unusual neck or body posturing - Typical presentation of uncomplicated GER: non-bilious effortless painless regurgitation in an apparently healthy infant with normal growth and without irritability – ‘happy spitter’ - Esophageal manifestations: vomiting, abdominal or substernal / retrosternal pain, poor weight gain, dysphagia - Extra-esophageal manifestations: respiratory symptoms (cough, laryngitis, wheezes), recurrent pneumonia, dental erosion, pharyngitis, sinusitis, recurrent otitis media - Check the growth parameters, nutritional status; look for anaemia, abnormal respiratory / abdominal signs Warning signs indicate alternative diagnoses or complications: choking, gagging, coughing with feeds or significant irritability, consistently forceful vomiting, bilious vomiting, onset of vomiting after 6mo, diarrhea, constipation, fever, lethargy, bulging fontanelle, hepatosplenomegaly, distended or tender abdomen, poor weight gain, anaemia Investigation: - Faecal occult blood - Pyloric USG for possible pyloric stenosis in baby with persistent forceful vomiting in first few months of age - Upper GI series: useful for the detection of anatomic abnormalities e.g. pyloric stenosis, malrotation, stricture, hiatal hernia. - pH-multichannel intraluminal impedance monitoring (pH-MII) - To detect movement of both acidic and non-acidic fluid, solid, air in esophagus - To detect temporal relationship between specific symptoms and reflux of both acidic and non-acidic reflux Abnormal study if reflux episode over 24hrs >100 in patients < 1 year, >70 in patients ages ≥1 year. - 24 hour oesophageal pH monitoring: measurement of acid reflux only Normal reference - Reflux index (percentage of total time that oesophageal pH < 4) < 12% in infant < 6% in age > 1 year - Prolonged reflux (> 5 minutes) < 10 episodes in infant 203 Section 5. Gastroninterstional system < 7 episodes in children - Endoscopy and biopsy: Indications: - Failure to respond to pharmacologic therapy or as part of the initial management of symptoms of poor weight gain, unexplained anaemia or faecal occult blood, recent pneumonia or haematemesis - To evaluate the presence and severity of injury from reflux of gastric contents to esophagus (i.e. erosion, ulcer, stricture, esophagitis, Barrett esophagus, adencocarcinoma) and exclude other disorders e.g. hiatal hernia, eosinophilic oesophagitis, Crohn’s disease, infection Management: Reassurance and education for non-complicated reflux. Lifestyle modification is first line treatment Infants: a. Positioning therapy - For infants birth to 12 months old, risk of SIDS outweighs the potential benefit of prone sleeping - Left side positioning during sleep and elevation of head at end of the bed may help. - Avoid semisupine positioning particularly in infant carrier or car seat after feeding because it exacerbates GER b. Small and frequent feed c. Milk thickening agents/ anti-reflux formula decrease frequency of overt vomiting. (but the reflux index is similar to control) Children and adolescent: a. Positioning therapy - For older children, slumped or supine postures should be avoided particularly in postprandial period. - Left-side sleeping posture, or prone and/ or elevation of head of the bed b. Avoid caffeine, spicy foods, large meal volume, late night eating and chocolate c. Weight reduction, cessation of smoking, avoid alcohol May consider trial of 2-4 week extensively hydrolysed or amino acid-based formulae in formula-fed infants; maternal exclusion diet (restrict milk and egg) in exclusive breastfed infants with GERD symptoms because cow’s milk protein allergy symptoms overlap with GERD, both conditions may co-exit in 42-58% of infants) Medications: a. Acid suppressant therapy - Proton pump inhibitors (PPIs) = mainstay of treatment. Esomeprazole (Nexium), approved in US for short-term treatment of GERD with erosive esophagitis aged from 1-12mo Omeprazole, lansoprazole approved in North America for > 1 year old. Pantoprazole approved for children > 5 years old. - Histamine-2 receptor antagonists Ranitidine Famotidine b. Prokinetic therapy (ESPGHAN practice guidelines conclude that there is insufficient evidence to justify its routine use) - A trial of domperidone (Motilium) <35kg 0.25mg/kg/dose tds; ≥35kg 10mg tds for 1 204 Section 5. Gastroninterstional system week, continue only when it is useful. - Metoclopramide - Erythromycin (Cochrane review concludes there is insufficient evidence to recommend its use in low or high doses for preterm infants <32 weeks’ gestation with feeding intolerance) c. Other agents - Surface protective agents: none is recommended for sole treatment for severe symptoms or erosive esophagitis - Antacids can be considered in mild infrequent symptomatic cases as on-demand basis, not for chronic use because of risk of aluminum toxicity Surgical therapy - Consider when medical treatment fails and in highly selected cases (i.e. underlying neurological impairment, chronic respiratory conditions or repaired esophageal atresia) - Fundoplication 205 Section 5. Gastroninterstional system Recurrent vomiting and/or regurgitation Vomiting/regurgitation and poor weight gain History and physical exam History and physical examination Are there warning signals ? Yes Evaluate further Are there warning signals ? Yes No No Further evaluation Adequate caloric intake? No Education Close follow-up Are there signs of complicated GER disease? Yes Yes No Workup for Failure to Thrive Consider: Upper GI series Abnormal? Uncomplicated infantile GER“Happy spitter” Yes Manage accordingly No Dietary Management Protein hydrolysate/amino acid formula Thickened feedings Increased caloric density Improved? Yes No testing; Education: Warning signals Reassurance. Consider: Thickened formula Resolves By 18 months of age Education Close follow-up No No Consultation with Pediatric GI Consider: OGD & biopsy Consultation with Pediatric GI Consider: acid-suppression therapy Consider: Hospitalization : Observe parent/child interaction Consider: NG or NJ tube feedings Fig 2 Fig 1 Approach to the infant with recurrent regurgitation and weight loss 206 Approach to the infant with recurrent regurgitation and vomiting Section 5. Gastroninterstional system Chronic Heartburn History and physical examination Education; Life-style change; PPI for 2-4 weeks Yes No Improves Continue PPI For 8-12 weeks Discontinue PPI Yes Consultation with Pediatric GI Relapse No Observation Fig 3 Approach to the older child or adolescent with heartburn. Ref : Journal of Ped Gastroenterology and Nutrition 2009;49:498-547 207 Section 5. Gastroninterstional system Chapter 70 - 24 hours oesophageal pH monitoring and pH-impedance monitoring (MII-pH) MC Chan Aims of the study: - To quantify reflux in patients with mainly extra-esophageal symptoms - To measure GER in patients not responding to antireflux treatment Indications: - Unexplained apnoea spell - Unexplained cough or choking - Unexplained colicky crying - Unexplained recurrent pulmonary infection or wheezing - Unusual neck or body posture - Prior to placement of feeding gastrostomy to determine the need for simultaneous anti-reflux procedures - Monitor response to treatment Not indicated: - Obvious GOR by history - Patients who may remove or destroy probes - Respiratory embarrassment from nasal probes - Gastric achlorhydria To eliminate the effect of drugs: - Prokinetic agents should be stopped for at least 48 hours - Antacids should be stopped for at least 24 hours - H2 antagonist / proton pump inhibitors should be stopped for at least 3-4 days Patient instruction before measurement: - Document mealtimes (beginning and end), position (prone, supine), symptoms and relevant events (e.g. correction catheter position, disconnection of skin electrode) - Avoid “acid” foods and carbonated beverages (e.g. Coca-Cola) - Avoid extremely hot or ice-cold drinks and food (as the reactivity of the pH electrodes is influenced by temperature) Potential complications: - Technical failure (device, catheter) - Probe misplacement (height, bronchus) - Mucosal trauma (bleeding, laceration) Catheter insertion and its correct position: Both pH and MII-pH catheters are passed transnasally preferably without sedation, the use of local anesthesia (e.g. intranasal anesthetic spray) may be beneficial in some children. Gel is often used to ease the passage through the nostrils, the gel should not be placed directly on the antimony electrodes because it may decrease its accuracy. The pH electrode should be positioned 2 vertebrae above the diaphragm at the level of the vertebral column. 208 Section 5. Gastroninterstional system Strobe formula (0.252 x body length [cm] + 5) to calculate the estimated appropriate probe position Confirm the position by X-ray before measurement. Comparsion between pH monitoring and impedance Parameter Acid GER Nonacid GER Superimposed acid reflux Gas reflux Height of reflux Chemical clearance Bolus clearance Postprandial GER pH monitoring Yes Blind Blind Blind 1 or 2 levels Yes Blind Blind MII-pH Yes Yes Yes Yes 6 levels Yes Yes Yes Definitions of reflux parameters: Liquid MII-reflux episode : decrease in impedance with ≥ 50% from baseline Acid MII reflux : with a pH <4.0 Weakly acid reflux : with a pH ≥4.0 but <7.0 Weakly alkaline reflux : with a pH ≥ 7.0 Gas MII-reflux episode : sharp increase of impedance > 3000 Ohm Mean bolus clearance time : time needed for a bolus to be cleared from the esophagus Bolus exposure index : the percentage of time that a bolus is present in the esophagus Mean acid clearance time : time needed for acid to be cleared from the esophagus (previously better known as the reflux index) 209 Section 5. Gastroninterstional system Chapter 71 - Helicobacter pylori infection MC Chan, WF Lau Gram-negative, spiral shaped, flagellated, microaerophilic bacteria Strongly associated with socioeconomic condition: > 80% in developing countries and 20-50% in developed countries Often acquired before 5 years of age; rate of infection 1% per year after 5 years old. Diagnostic tests: Invasive: Endoscopic gastric biopies (antrum, corpus) Rapid urease (CLO) test and histopathology +/- culture Non-invasive: Urea breath test Stool antigen For the diagnosis of H pylori infection is based on either a positive histopathology + positive rapid urease test or a positive culture. Associated disease: Peptic ulcer - present in 60% in adult with gastric ulcer - 80% adults and 90% children with duodenal ulcer Non-ulcer dyspepsia - all with chronic gastritis but most are asymptomatic Gastric cancer - adenocarcinoma ~ 1% infected patients - mucosa-associated lymphoid tissue (MALT) lymphoma Atherosclerosis Eradication rate ~ 92% Clarithromycin resistant H pylori in HK is low (~10%) 1st line eradication regimen: Amoxicillin 50 mg/kg/day up to 1g BD Clarithromycin 20 mg/kg/day up to 500 mg BD Esomeprazole 1 mg/kg/day up to 20 mg BD For 1-2 weeks 2nd line eradication regimen: PPI + levofloxacin + amoxyicillin BD for 14 days Metronidazole 20mg/kg/day up to 500mg BD to replace amoxicillin if amoxicillin allergy Reliable non-invasive test to confirm eradication should be performed at least 4-8 weeks following completion of therapy. 210 Section 5. Gastroninterstional system Chapter 72 - Recurrent abdominal pain WF Lau Definition: At least 3 attacks in at least 3 months Severe enough to interfere with normal daily activities 10-15% children between 4 -16 years old has recurrent abdominal pain Another 10-15% has chronic pain with normal activities Rare before 5 years of age Peak at 10-12 years of age Before 9 years of age, boys and girls equally affected; boys to girls 1:1.5 afterward 5-10% with organic causes Presentation: Paroxysmal, variable in severity 50% last for < 1 hour, 90% < 3 hours Periumbilical or mid epigastric region usually no radiation Clustering of pain alternating with pain free periods of variable length No temporal relation with meals, exercise, stress At least 50% with associated symptoms (headache, pallor, dizziness, nausea, fatigability) Differential diagnoses: Functional - Irritable bowel syndrome - Functional abdominal pain - Abdominal migraine - Aerophagia Infection - GI: Giardia, TB, Yersinia, Campylobacter - Urinary tract Inflammation - Inflammatory bowel disease - Coeliac disease - Eosinophilic gastroenteropathy GI obstruction - Malrotation, postsurgical adhesion, angioneurotic oedema, constipation Gynaecological - Dysmenorrhoea, endometriosis, pelvic inflammatory disease, ovarian cysts Others - Pancreatitis, hepatitis - PUJ obstruction, - Acute intermittent porphyria - Physical / sexual abuse - School phobia, conversion reaction, somatization disorder 211 Section 5. Gastroninterstional system Alarm signals on history - Localization of pain away from midline - Pain awakening patient from sleep - Pain radiated to other area - Repeated vomiting or altered bowel pattern like profuse diarrhoea - GI bleeding - Constitutional symptoms (fever, rash, arthralgia) - Consistent sleepiness after pain attack - Loss of appetite - Positive family history of IBD, peptic ulcer - Children under 5 years old Alarm signals on physical exam - Growth disturbance - Localized tenderness - Organomegaly - Joint inflammation - Perirectal disease (ulcer, fistula, skin tags) Alarm signals on investigation - Elevated inflammatory markers - Anaemia - Hypoalbuminaemia - Positive stool occult blood Management - Refer to GI clinic 212 Section 5. Gastroninterstional system Chapter 73 – Cow’s milk protein allergy DK Ng Introduction: Commonly presents in neonatal and infancy period 50-80% of cases presents with gastrointestinal symptoms 20-40% cutaneous symptoms 4-25% respiratory symptoms Symptoms and signs: Gastrointestinal: vomiting, diarrhoea, abdominal colic and bloating, constipation and in severe cases, haematemesis and bleeding per rectum (enterocolitis syndrome) Refusal to feed Dehydration Failure to thrive Urticaria, atopic eczema, angioedema Rhinitis, asthma Anaphylactic shock Diagnosis: Peripheral eosinophilia is uncommon RAST test and skin prick test Frequently negative in neonates and infants A positive skin prick test may not necessarily mean clinical problem but a negative skin test result has a high predictive accuracy (estimated to be > 95%) in older children Stool for eosinophils Stool for occult blood OGD / colonoscopy with biopsy Infiltration of the mucosa and submucosa with eosinophils (> 5-20 per high power field) Management: Resuscitate if necessary Advise breastfeeding mother to avoid dairy products Avoidance of cow’s milk products for 1-2 years. Over 50% of children with cow’s milk protein allergy may also be allergic to soy protein. 5% may be allergic to semi-elemental milk like Pepti-Junior, and elemental diet like Neocate may be necessary in such cases. A period of total or partial parenteral feeding may be necessary. Open challenge with Cow’s milk should be offered at 2-year-old to confirm remission. 213 Section 5. Gastroninterstional system Chapter 74 - Management of Idiopathic constipation in children MC Chan, L Leung Definition of constipation: delay or difficulty in defecation present for 2 or more weeks (Ref: NICE guideline May 2010, NASPGHN guideline 2006) Features suggesting constipation: (table 1) Child <1yr Child >1yr <3 complete stools per week (type 3/4) # <3 complete stools per week (type 3/4)# Hard stool Overflow soiling, commonly very loose and smelly Rabbit droppings (type1)# Rabbit droppings (type1)# Large, infrequent stools that can block toilet Distress on stooling Poor appetite that improves with passage of large stool Bleeding asso with hard stool Intermittent abd pain with passage of stool Straining Retentive posturing: typical straight legged, tiptoed, back arching Straining Anal pain Painful bowel movements and bleeding aso with hard stools Previous episode of constipation Previous or current anal fissure # Bristol Stool Form Scale (adapted from Lewis SJ, Heaton KW (1997) stool form scale as a useful fuide to intestinal transit time) Type 1 Type 2 Type 3 Type 4 Type 5 Type 6 Type 7 Separate hard lumps, like nuts (hard to pass) Sausage-shaped but lumpy Like a sausage but with cracks on its surface Like a susage or snake, smooth and soft Soft blobs with clear-cut edges (passed easily) Fluffy pieces with ragged edges, a mushy stool Watery, no solid pieces; entirely liquid Table 1. Normal frequency of bowel movements: Age 0-3 months - breast-fed - formula fed 6-12 months 1-3 years >3 years Bowel movements per week Mean bowel movements per day 5-40 5-28 5-28 4-21 3-14 2.9 2.0 1.8 1.4 1.0 (Adapted from Fontana M. Bianch C, Cataldo F, et al. Bowel frequency in healthy children. Acta Paediatr Scand 1987;78:682-4.) 214 Section 5. Gastroninterstional system Physical exam: Growth, Abdomen, anal inspection, spine, neurological exam. At least one PR is recommended: assesses perianal sensation, anal tone, the size of the rectum, and the presence of an anal wink, the amount and consistency of stool and its location within the rectum. Investigations: AXR – not indicated to establish the presence of fecal impaction if PR reveals large amounts of stool – Helpful in obese/ refuses PR or good history of constipation but no large amounts of stool on PR Barium enema – Usually unnecessary beyond infancy – May be indistinguishable from cases of functional constipation with ultra-short-segment Hirschsprung; may fail to show transition zone in cases of total colonic Hirschsprung disease Management algorithm: Establish the diagnosis of constipation (2 or more symptoms from table 1) Any RED FLAG symptoms or signs? History Signs From birth or first few weeks of life Abnormal appearance/ position/ patency of anus: fistulae, bruising, multiple fissures, tight or patulous anus, anteriorly placed anus, absent anal wink Failure to pass meconium/ delay >48hrs Gross abdominal distension after birth in term baby “Ribbon stools” Asymmetry or flattening of the gluteal muscles, evidence of sacral agenesis, discoloured skin, naevi or sinus, hairy patch, lipoma, sacral dimple, scoliosis Faltering growth Lower limb deformity e.g. talipes Abnormal neuromuscular signs unexplained by any existing condition e.g. CP Previously unknown or undiagnosed Abnormal reflexes lower limb weakness, locomotor delay Abdominal distension with vomiting No Yes Idiopathic constipation Reassure parents of suitable treatment but may take several months for symptom resolution. Assess for faecal impaction (overflow soiling +/faecal mass palpable abdominally and/ or rectally) 215 Test for hypothyroidism, Coeliac disease, hypercalcaemia, lead toxicity, cow milk protein allergy (trial of milk free diet), spinal abnormalities, Hirschsprung’s disease Section 5. Gastroninterstional system Management : ** 1. Faecal disimpaction if there is faecal impaction (PEG or lactulose/ stimulant laxative) 2. Maintenance (PEG or lactulose +/- stimulant laxative) 3. Education, Diet & lifestyle modification, bowel training, diary 1. FAECAL DISIMPACTION i. PEG (i.e. Klean Prep) + lactulose ii. Add a stimulant laxative (e.g. Senna) with or without lactulose for short periods if Klean Prep is not tolerated or fail to disimpact. iii. Use glycerin suppository in infants; suppository or fleet enema in children ≥ 2 yrs as last resort only after discussion with parents. Problems with phosphate enemas: mechanical trauma to rectal wall, severe hyperphosphatemia and hypocalcemia which may be lethal. iv. Inform families that disimpaction treatment can initially increase symptoms of soiling and abdominal pain v. DO NOT perform manual evacuation of the bowel under anaesthesia unless all oral and rectal medications have failed vi. Review all children undergoing disimpaction within 1-2 weeks 2. MAINTENANCE THERAPY i. Start maintenance therapy as soon as the patient’s bowel is disimpacted ii. Reassess the patient frequently to ensure they do not reimpact and assess issues in maintaining treatment e.g. taking medicine and toileting iii. PEG (i.e. Klean Prep) + lactulose as the first-line treatment iv. Adjust the dose of PEG according to symptoms and response. As a guide for patient who have had disimpaction the starting maintenance dose might be half the disimpaction dose (table 2) v. Add a stimulant laxative (e.g. Senna) intermittently, for short periods if PEG does not work, or not tolerated vi. Continue medication at maintenance dose for several weeks after regular bowel habit is established. Children who are toilet training should remain on laxatives until toilet training is well established. vii. Do not stop medication abruptly: gradually reduce the dose over a period of months in response to stool consistency and frequency. 3. EDUCATION, DIET & LIFESTYLE (DO NOT use dietary interventions alone as first-line treatment) i. Explain pathogenesis of constipation, remove blame if soiling, needs months of treatment. Negotiated and non-punitive behavioural interventions. Consistent, positive and supportive attitude of family. ii. Scheduled unhurried time on toilet after meals (30min after meal for 10-15min). 216 Section 5. Gastroninterstional system iii. iv. v. vi. Use of encouragement, star chart and positive reinforcement. Posture in defecation: hips abducted and flexed with feet support Balanced diet should include adequate fibre (whole grain, fruit and vegetable) and fluid intake. Sorbitol in prune, pear and apple juices can soften stool. For 1-8yo: 4-5 glasses of water per day (complimentary water) For 9-18yo: 7-10 glasses of water per day (complimentary water) Advise daily physical activity Table 2: laxative recommended dose A. Stimulant laxatives Bisacodyl (Dulcolax) (NICE recommended doses) PO 4-18yo: 5-20mg once daily PR (suppository) 2-18yo: 5-10mg once daily Senna (1 tab = 7.5mg) 2-4yo: 1/2 – 2 tab once daily 4-6yo: 1/2 – 4 tab once daily 6-18yo: 1-4 tab once daily C. Osmotic laxatives Lactulose 1 month to 1 year: 2.5ml BD, adjust according to response 1-5 years: 2.5-10ml BD, adjusted 5-18 years: 5-20ml BD, adjusted B. Polyethylene glycol (PEG) 3350 + electrolytes (i.e. Klean Prep 68.6g/pack) - Dilute 1 sachet of Klean Prep to 1000ml - Advise to take Klean Prep in the early evening, as bowel movement starts 1-2 hours after Klean Prep. Disimpaction: <1yr 55-110ml daily (3.8g – 7.5g) 1-5yrs220ml (15g for 1st day) increase to 440ml (30g) daily for 2 days, and up to 660ml (45g) daily 5-12yrs 440ml (30g) (1st day) increase in steps of 220ml daily to max of 1000ml (68.6g) daily Maintenance: <1yr 55-110ml daily (3.8-7.5g) 1-5yrs 110ml (7.5g) daily; adjust dose to produce regular soft stools (max 330ml (22.5g) daily) 5-12yrs 220ml (15g) daily; adjust dose to produce regular soft stools (max 440ml (30g) daily) 217 Section 6. Renal system Section 6: Renal system 218 Section 6. Renal system Chapter 75 – Urinary Tract Infection in children 2-24 months L Leung Definitions: Acute pyelonephritis/ upper urinary tract infection: defined as bacteriuria with i) fever ≥38C or ii) loin pain/tenderness (NICE). Cystitis/ lower urinary tract infection (bladder inflammation): dysuria, frequency, suprapubic pain, girls >2yrs. Asymptomatic bacteriuria: bacteriuria without symptoms. Diagnosis History: Look for risk factors for underlying pathology - bowel and bladder habits (look for soiling, constipation and voiding dysfunction like frequency, urgency, squatting or other holding manoeuvres, day-wetting, poor or interrupted stream, straining during voiding, prolonged voiding) - past history of similar attacks or unexplained febrile episodes - AN diagnosis of renal abnormality - family history of VUR or renal disease Physical examination: - BW, Ht, BP - abdomen (kidney, bladder) - genitalia including phimosis - spine, LL reflex Investigations: - blood culture if clinically indicated - RFT - CRP and ESR (for acute pyelonephritis) - (G6PD status if not known) 219 Section 6. Renal system Figure 1 Strategy to diagnose febrile UTI Fever with no obvious focus of infection Suspected UTI and ill Suspected UTI and not ill SPT or catheter urine for urinalysis and culture (+ other sepsis workup), followed by antibiotics Option 1: SPT or catheter urine for urinalysis and culture; or Option 2: Bag/midstream urine for urinalysis, if positive, proceed to SPT or catheter or midstream urine for urinalysis and culture Start antibiotics if SPT/catheter/MSU urine sample shows positive urinalysis Likelihood Ratios of different enhanced urinalysis tests Pooled +ve Tests Likelihood R (CI) Pooled –ve LE +ve 5.5 (4.1-7.3) 0.26 (0.18-0.36) Nitrite +ve 15.9 (10.7-23.7) 0.51 (0.43-0.60) Nitrite or LE +ve 6.1 (4.3-8.6) 0.20 (0.16-0.26) Nitrite and LE +ve 28.2 (17.3-46.0) Pyuria: 5.9 (4.1-8.5) > 5/hpf (centrif) 3 > 10/mm (uncentrif) Bacteriuria 2.5-3.9 7.7 likelihood R (CI) 0.37 (0.26-0.52) 0.27 (0.20-0.37) # 7# 14.7 (8.6-24.9) Gram stain (centrif) 18.6 Bacteria seen 4.8# 0.19 (0.14-0.24) # Pyuria or bacteriuria 4.2 (2.3-7.6) 0.11 (0.05-0.23) Pyuria and bacteriuria 37.0 (11.0-126) 0.21 (0.13-0.36) Any +ve test (0.8-35.9) (0.01-5.38) From : Whiting P. 2005 Stratified by <2 yrs (less reliable) # Moyer 2000 220 0.32 Section 6. Renal system Diagnostic criteria for Positive Growth for UTI Confirmed UTI Scenario : fever +/- urinary symptoms + pyuria (by dipstix or microscopy) Any +ve growth of SPT urine Yes uropathogens >10^4, single growth Yes Catheter urine 10^3-10^4, or ≥2 uropathogens No <10^3 No >10^5, single growth Yes Clean catch urine 10^4-10^5, or ≥2 uropathogens No <10^4 No Scenario : asymptomatic + negative urinalysis Colony-forming units on culture SPT/catheter/ Clean catch urine Suspected UTI Yes No Yes No Contaminant or asymptomatic bacteriuria Any growth * Urine should be plated immediately or sent on ice within 4 hours. Overnight samples should be in boric acid bottles (follow recommended volume). **All tests have False –ve results. Clinicians should use clinical criteria for their decisions when urine testing does not support the findings Treatment Antibiotic Treatment: Pyelonephritis If patient is toxic, vomiting or dehydrated (or <2 months), admit to hospital for IV Antibiotics and fluid therapy. For ≥2 months, Switch to oral AB once fever subsided provided compliance ensured. For stable, non-toxic patients ≥2 months who can tolerate and likely compliant with oral AB, oral antibiotics can be given. Treatment should last for 7-14 days. (usually 10 days) Empirical antibiotics depend on local susceptibilities. Usual choices for oral treatment include cefuroxime, amoxicillin/clavulanic acid (Table 1) or co-trimoxazole (not for <3 mths). Usual choices for parenteral therapy: amoxicillin/clavulanic acid, 2nd or 3rd generation cephalosporin or aminoglycoside +/- ampicillin (to cover enterococci). For ESBL organisms: oral Augmentin; if sick: IV meropenam if blood culture +ve, give iv antibiotics for 10-14 days Antibiotic Treatment: Cystitis/lower UTI: oral antibiotics for 3-5 days. Asymptomatic bacteriuria should not be treated. Patients with UTI who do not show expected clinical response to AB should have urine re-cultured, co-existence of septicaemia and meningitis should be considered, and US kidneys performed urgently for abscess/ obstructive HN or complicated malformations. 221 Section 6. Renal system Table 1 Urinary tract infection Age <3 months >=3 months to children <40kg Augmentin preparation 156mg/5ml(4:1) Amoxicillin 30 mg amoxicillin/kg/day BD 475mg/5ml(7:1) Amoxicillin 40mg/kg/day BD (Max. daily dose 875mg) Clavulanate 7.5mg/ kg /day Clavulanate 6.4mg/kg/day Follow up Imaging See Fig 2a, 2b DMSA scan (at 6 mths after UTI) is recommended when: 1) ≥ Grade III VUR is detected on VCUG 2) patient has recurrent febrile UTI. Antibiotic prophylaxis Antibiotic prophylaxis should not be routinely prescribed to young children after first time UTI. No need prophylaxis (whilst waiting for US) unless decided to do VCUG When VCUG is performed for risk factor criteria and ≥Grade 3 VUR is diagnosed, antibiotic prophylaxis can be considered, taking into account parental preference. If UTI recurs, and VCUG reveals ≥Grade III VUR, antibiotic prophylaxis is recommended. Surgical referral • If UTI recurs (2nd UTI), those with ≥Grade III VUR, and significant scarring on DMSA may be offered a surgical referral to discuss the option of surgical intervention as an alternative to AB prophylaxis. • If UTI recurs again (3rd UTI) despite AB prophylaxis, those with ≥Grade III VUR (with or without scarring) should be offered a surgical referral. Others • It is important that the family be educated to recognize the symptoms and signs of recurrent UTI. Early recognition and treatment of acute pyelonephritis will limit renal damage. • Dysfunctional elimination syndromes and constipation should be addressed. • Drink adequate amounts of water • Perineal hygiene, Urination should not be delayed. Figures useful in counseling parents From local cohort of 820 children <24 months old seen in HA hospitals in 2005-6 with full set of imaging done, VUR found in 24%, of which Gd III 6%; Gd IV 3.9%; Gd V 0.6%. Using Risk factors + USG criteria + FU as criteria for MCUG and DMSA chance of missing abnormalities that potentially benefit from early detection (high grade reflux or significant renal scars) is 0.8%. 222 Section 6. Renal system * * Risk factors - Severe sepsis or septicaemia - Palpable abdominal mass. - Impairment of baseline renal function - Hx abnormal urine stream - UTI due to non-E coli organisms - No clinical response to appropriate antibiotics within 72 hrs - VUR first degree relative Major references: HK- HA Paed COC QA subcommittee Clinical Guideline on The Diagnosis and Initial Management of Urinary Tract Infections in Infants and Children aged 2 to 24 months (2013) UK - NICE Guidelines 2007 USA - AAP. Pediatrics 2011; 128:595-610. Italy - Ammenti et al. Acta Paediatr 2012; 101(5):451-457 Australia - Williams et al. J Paediatr Child Health 2012; 48(4):296-301 223 Section 6. Renal system Chapter 76 – Monosymptomatic Nocturnal Enuresis PH Chan, L Leung Terminology Enuresis – wetting during sleep in a child ≥ 5 years of age Monosymptomatic enuresis (MNE) – Enuresis without any lower urinary tract symptoms. Non-monosymptomatic enuresis (NMNE) – Enuresis with other lower tract symptoms Primary enuresis – Enuresis in a child who has previously been dry for <6 months Secondary enuresis – Enuresis in a child who has previously been dry for at least 6 months Evaluation: Aim to identify 1. Organic diseases (neurogenic bladder, UTI, polyuric state like DM, DI, hypokalemia) 2. Voiding dysfunction/ lower urinary tract symptoms 3. Psychiatric comorbidities (e.g. ADHD) 4. Constipation History General - Health and development. Weight loss? Excessive thirst? UTIs? Timeframe - Primary/secondary enuresis? Frequent/sporadic accidents? Bladder – Voiding dysfunction e.g. frequency, urgency, dysuria, straining, weak or intermittent stream Bowel - Constipation symptoms, fecal incontinence? Behaviour - Problems at home or at school? Distressed by enuresis? Previous treatment strategies - Which strategies have been used? Have they been used correctly? Others - Enuresis in the family? Difficult to arouse from sleep? Sleeping arrangements. - Habitual snoring, observed obstructive apnea Physical Examination General – Well-being, growth, BP Back – Skin stigmata for spinal dysraphism, spinal deformity Lower limbs – Neurology External genitalia – Malformation, phimosis Constipation – Abdominal (fecal) mass, soiling on underpants, +/- PR 48-hour frequency-volume chart (available on Department Web) Daily fluid intake and urine output – Identifies those with polydipsia/ polyuria Voiding frequency/ urgency – Identifies those with urinary frequency (>7x/day)/ urgency Maximum voided volume – when compared to expected bladder capacity (30 x age +30 mL, max 390mL), identifies those with bladder pathology (detrusor instability or underactivity) Nocturnal urine volume – (diaper weighing) When compared to expected bladder capacity, help to plan treatment Investigations Monosymptomatic enureisis: MSU x R/M, culture, protein, glucose, EMU x osmolality (>700 mOsmol/L rule out concentration defect Secondary nocturnal enuresis or diurnal urinary incontinence: Plus RFT, Ca, Urine Ca/Cr Initial evaluation suggestive of NMNE: Refer renal clinic, may need urodynamic study. If suspect neurogenic bladder or posterior urethral valve: may need US with post void residue, or MCU. 224 Section 6. Renal system Treatment General advice – for all 1. Treat constipation (Regular visit to toilet every night after dinner, foot support, stool softener etc.) 2. Liberal fluid and solute during the day and limit fluid and solute during evening (practically – avoid large dinner and food after dinner, except fruit) 3. Empty bladder before retiring 4. Easy access to bathroom (may need night light) 5. No lifting/ diaper/ training pants; protect bed (e.g. with plastic sheeting) 6. Routine awaking is unnecessary. 7. Child should bear age-appropriate responsibilities after wetting (e.g. soak or wash underpants) 8. Star chart – charted by child under supervision. Lots of praise for dry night Specific treatment – for those >= 6 years of age The Enuresis Alarm • Good for motivated child and family • Early initial follow-up (2-3 weeks) is essential • The parent may help child wake up for initial 1-2 weeks, (but not do everything for him.) • Fill in ”Enuresis alarm recording sheet” (on Dept. web) • Praise Smaller wet patch. • Use consistently every night without interruptions, until 14 consecutive dry nights or 4 months without effect. If response, can try load with increased fluids before bed to enhance response. Explain anticipated response: gradual smaller wet patch; usually by 3-4 weeks: 3-4 dry nights/ week. Success rate: 65-100% (85%) after 4-6 months, enhanced by support from parents and therapist Relapse rate: 9-23% (23%), most respond quickly to another course of alarm treatment If fail: Praise them for effort; say bladder not ready yet and try again later and advise follow-up Desmopressin Increase antidiuretic activity of DDAVP Most efficient in children with nocturnal polyuria (document with frequency-volume chart) Choose between daily medication or administration before important night e.g. camping • Desmopression 200–400µg PO taken at least 1 hour before sleep • Desmomelt 120-240µg PO taken 30-60 mins before sleep Restrict fluids after dinner to <200mL till awakening next morning Water intoxication and seizures reported Headache, abdominal pain, nausea Cure rate 25% Response rate (half wet nights) 70% Most relapsed after off drugs (5.7% still dry) Priority of treatment General advise PLUS Treat constipation Treat daytime bladder symptoms Treat enuresis Referral to Renal Clinic 1. Non-monosymptomatic enuresis 2. Those who required specific treatment 225 Section 6. Renal system Chapter 77 - Nephrotic syndrome L Leung Definition : Nephrotic syndrome (NS) = heavy proteinuria severe enough to cause hypoalbuminaemia, and usually hypercholesterolaemia and oedema. Nephrotic range proteinuria is defined as spot protein / creatinine ≥ 200 mg/mmol or proteinuria ≥ 40 mg/m2/hour or ≥ 1,000 mg/m2 per day. Pre-steroid renal biopsy should be considered in those whose features make minimal change NS less likely: - Age <1 year or >12 years - Macroscopic haematuria - Persistent hypertension - Low C3, Hep B or C positive - Impaired renal function Post steroid-treatment: renal biopsy if steroid resistance or in steroid dependency before use of cyclophosphamide (optional) or cyclosporin A Table 1. Definition of terms used in children with NS Remission Dipstick negative or trace proteinuria for 3 days or urinary protein excretion < 4 mg/m2/hour Relapse Dipstick >= 2+ proteinuria for 3 consecutive days; or patient found to have 3-4+ proteinuria plus edema Frequent relapses (FR) 2 or more relapses within first 6 months after initial response, or 4 or more relapses within any 12 months period Steroid dependency (SD) 2 consecutive relapses during tapering of glucocorticoid, or within 14 days of cessation Steroid resistance (SR) Persistent proteinuria despite full-dose prednisolone for 4 weeks, followed by 3 x 1g / 1.73 m2 IVI pulses of methylprednisolone. (Niaudet) Steroid-responsive in 90% children. 70% will have relapses, ~50% FR or SDNS. 80% NS due to Minimal Change, GN. Secondary causes of NS • Infection: HepB, HepC, Syphilis,TB, Mycoplasma, HIV, congenital CMV/ toxo/ rubella • Systemic diseases: HSP, SLE, vasculitis • Structural glomerular changes (eg. Alport) • Malignancy: lymphomas, leukaemias, solid tumours like nephroblastoma • Drugs: NSAID, Antimicrobials (ampicillin, rifampicin, cephalosporins), Lithium, D-penicillamine, bisphosphates, Sulfasalazines. Investigations CBP, RFT, LFT, cholesterol and triglycerides, ANF, anti-dsDNA, C3C4, Ig pattern, HBsAg, HBeAg, Hep C, antibodies to measles and varicella, EBV, CMV. Urinalysis: RBC, casts; 24-hour urine x protein and creatinine clearance 226 Section 6. Renal system Mantoux test: if positive, exclude TB before treatment Acute complications of NS Hypovolaemia, hypervolaemia Infections: peritonitis (Strep. pneumoniae, E. coli), cellulitis Venous, and rarely, arterial thrombosis, rare in Chinese children Anasarca leading to respiratory distress, skin breakdown and cellulitis General aspects of management of children with NS Assess fluid status Hypovolaemic children may appear tired, have decreased urine output, abdominal pain, prolonged cap refill, tachycardia, postural hypotension (but may be hypertensive from vasoconstriction). Lab tests may show raised Hct, urine Na < 10 mmol/l or urinary FENa of < 1%, Urine K+ / Urine K+ + Urine Na+ > 60% (indicating aldosterone activation). However, urine Na may also be low in hypervolaemic NS from primary Na retention. Those with hypovolaemia may be promptly treated with 10-20ml/kg 4.5% albumin. Diet: salt restriction to 2-3 mEqNa/kg/day, max 2g/day, but generally not need fluid restriction; adequate in protein. When on steroids, recommend a nutritious, relatively low-fat diet. Oedema: If severe symptomatic oedema with normal intravascular status: frusemide +/spironolactone. Caution: as may precipitate shock in a volume depleted child. In oedematous children with marked hypoalbuminemia, may give daily or bd salt-poor albumin 1 g/kg over 4 hours with IV frusemide 1-2mg/kg. Caution: may precipitate pulmonary oedema in hypervolaemic patients. Hypertension: may be due to hypervolaemia or excessive vasoconstrictive response to hypovolaemia. Latter: urine Na low. Former: raised venous pressure, cardiomegaly. Treat with atenolol 0.5-1 mg/kg or nifedipine 0.25-2 mg/kg. Others: Encourage mobilization. Prophylactic antibiotics not recommended, but infections to be promptly treated. Education of parent and child about NS, side effects of treatment and regular urine dipstick monitoring at home to identify early relapse. Specific therapy for Nephrotic Syndrome Initiating and maintenance of steroids (HKPNS) Prednisolone 60 mg/m2 (max 60 mg) x 4weeks; as single daily morning dose. 40 mg/m2 alternate day for 4 weeks, then 30mg/m2 alternate day for 4 weeks, 20mg/m2 alternate day for 4 weeks, 10mg/m2 alternate day for 4 weeks, 5mg/m2 alternate day for 4 weeks, then off (Total treatment duration of 6 months). For late responder (those could not achieve remission in first 2 weeks, ~ 20% responders) Prednisolone 60mg/m2/day (maximum 60mg/day) for 6 weeks, followed by 40mg/m2 on alternate day (maximum 60mg alternate day) for 6 weeks, then similar tapering doses for 4 weeks each time. (Total treatment duration of 7 months) Monitor for steroid side effects: Cushingoid features, weight gain, gastric irritation, ulcers, pancreatitis, hypertension, fluid retention, bone demineralization and avascular necrosis, decreased immunity, posterior subcapsular cataract, diabetes, pseudotumour cerebri, proximal myopathy, growth retardation, psychological changes (depression, psychosis, mood lability). 227 Section 6. Renal system Treatment of relapses 60 mg/m2 till protein free 3 days consecutively, then 40 mg/m2 alternate day therapy for 4 weeks, then taper. Other issues related to steroid therapy Hypothalamic-Pituitary-Adrenal axis suppression occurs when steroid treatment lasts > 2 weeks. Needs 2-3x physiological dose during surgery, trauma, infection. Children already on larger than physiologic doses of steroid do not need additional coverage. Give coverage for 1 year post-steroid weaning: hydrocortisone 1-2 mg/kg Q6H x 24-48 hours post-op. Osteoporosis: those on more than 5 mg daily or > 15 mg alternate day for at least 3 months are at risk of osteoporosis. Measures to decrease risk: Children: elemental calcium (diet or supplement) 800 mg/day for 1-5 yr olds, 1,200 mg/day 6-10 yr olds, and 1,500 mg/day for 11-24 yr olds + supplemental Vit D 400 IU/day increase physical activity (especially weight bearing activities such as walking). avoid heavy lifting, high-impact aerobics and contact sports. Infections and immunizations a. Vaccines should be given ideally when patient is in remission. Killed vaccines can be given any time. Avoid live vaccine when on high dose steroids or other immunosuppressives. Live vaccines preferably given when child has been off steroids for 6 weeks (best 3 months after stop steroids or cyclosporine, or 6 months after stop cyclophosphamide) or at least, on low-dose (< 0.5 mg/kg) alternate day steroid. b. Children not previously immunized against measles should receive immunoglobulin when exposed. Check chickenpox / measles antibody status. Varicella vaccine, 2 doses 4 weeks apart, should be given to all non-immune nephrotic patients on immunosuppressives, ideally when child in remission & on low alternate day steroids or off steroids. If a susceptible child on steroids is exposed to chickenpox, varicella-zoster immunoglobulin VariZIG should be given within 96 hours of exposure. Steroid should be tapered to ≤ 1 mg/kg/day until incubation period has passed. Acyclovir should be given if varicella does develop. Varicella vaccine should be given 5 months after VariZIG. c. d. Pneumococcal vaccine is recommended for all nephrotic children (Table 2) ideally when child in remission & off daily steroid, though high antibody levels still found when given whilst child on daily high dose steroid. e. Give annual Influenza vaccine. f. Household contacts of children on high dose prednisolone should be given inactivated polio rather than live oral polio. g. Nephrotic children with positive tuberculin reaction and no active TB should receive Isoniazid prophylaxis for 6 months if interferon-gamma is +ve. 228 Section 6. Renal system Table 2. Suggested pneumoccocal vaccine schedule for nephrotic children (AAP 2010) Recommendations Age Previous Doses none PCV13 as normal schedule ≤ 23 months 24-59 months 4 doses PCV13 1 dose 23PS at 24 months, at least 6-8 weeks after last PCV7 2nd dose 23PS, 5 years after 1st dose 23PS 1-3 doses PCV3 1 dose PCV13 1 dose 23PS, 6-8 weeks after last PCV13 2nd dose 23PS, 5 years after 1st dose 23PS 24-59 months none 2 doses PCV13 6-8 weeks apart 1 dose 23PS, 6-8 weeks after last PCV13 2nd dose 23PS, 5 years after 1st dose 23PS 1 dose 23PS 2 doses PCV13 6-8 weeks apart, at least 6-8 weeks after last 23PS 1 dose 23PS, 3-5 years after 1st dose 23PS 6-18 years none 1 dose PCV13 1 dose 23 PS 6-8 weeks after last PCV13. 2nd dose 23PS 5 yrs after 1st dose 23 PS PCV13= pneumococcal conjugate vaccine 23PS= 23-valent pneumococcal polysaccharide vaccine. Children with frequently relapsing (FRNS) or steroid dependent (SDNS) nephrotic syndrome Renal biopsy should be considered. Consult Renal team. May be maintained on Prednisolone 0.1-0.5 mg/kg/alt day for 3-6 months then reduce. If child relapses on > 0.5 mg/kg/alt day or is steroid-toxic: may require alternative drugs to control the disease and decrease steroid side effects. Levamisole: effective for milder disease; 2.5 mg/kg/alt day, usually for 2-3 yrs if remission maintained. Cyclophosphamide: more effective for FRNS, can keep 70% SDNS in remission some evidence 12-week course of cyclophosphamide 2 mg/kg/day is superior to 8-week course 3 mg/kg/day. Total cumulative dose should be less than 170 mg/kg to minimize long-term risks of azoospermia and ovarian fibrosis. Other side effects: bone marrow suppression, hair loss, haemorrhagic cystitis, long term increased risk of malignancy Cyclosporin A: indicated where relapses occur after cyclophosphamide. However, children may become cyclosporin A dependent. Side-effects include hypertension, nephrotoxicity, increased K+, decreased Mg2+, hypertrichosis and gingival hyperplasia. Mycophenolate mofetil: Useful, especially in children who are at risk of nephrotoxicity after on prolonged course of Cyclosporin A. Steroid sensitive NS generally has a good prognosis and likely to improve with time. When potentially toxic drugs are used; one has to balance the benefit against the potential side effects of the drugs. Steroid resistant NS Renal biopsy. Consult Renal team. 229 Section 6. Renal system Chapter 78 - Fluid and electrolytes therapy B Pau, L Leung, DK Ng Principle: Maintain fluid homeostasis. – Replacement of deficit – Maintenance therapy – Replacement of ongoing loss: excessive urine loss , GI loss. Skin (infective/ immune/ burns). 3rd space loss. Hyperventilation/ fever. Daily requirement of fluid can be estimated from body weight: First 10Kg 100mls/kg Subsequent 10Kg 50mls/kg Remaining Body Wt over 20Kg 20mls/kg For example: A 25Kg child would require: 10 x 100mls + 10 x 50mls + 5 x 20mls for a total 1600mls/day Clinical assessment of fluid deficit: (1% deficit = 10mls/Kg) - Mild dehydration (Deficit: infant 5%, children 3%). History of vomiting/ diarrhea, decreased intake, decreased urine output, thirst. P/E usually unremarkable. - Moderate dehydration (Deficit: infant 10%, children 6%). History of fluid loss. P/E: decreased skin turgor, weight loss, sunken eyes +/- fontanel, slight lethargy, and dry mucous membranes. - Severe dehydration (Deficit: infant 15%, children 9%). Cardiovascular instability (e.g. prolonged CRT, skin mottling, tachycardia, hypotension) and neurologic involvement (e.g. irritability, coma). Principles of Fluid therapy - Use oral hydration first (including in hyperNa and severe dehydration) unless oral intake not tolerated/ contraindicated - In GE cases, oral rehydration with Oral Rehydration Solution (ORS) 40-50mls/Kg for initial deficit over 3-6 hrs (longer duration for older children), frequently in small amounts (minimal 240ml for <5 yrs and 480 ml for ≥5 yrs). Replace on-going loss: 5mls/Kg per large watery diarrhoea and 2mls/kg per vomit. (Please refer to KWH GE guidelines for details) - Traditionally dehydration is replaced over 24 hrs (unless hypertonic dehydration) in addition to daily maintenance fluids. Recent literature are advocating faster rehydration in the absence of hypernatraemia. (Replace deficit in moderate / severe dehydration with 40-50ml/kg isotonic solution (NS or Ringer’s lactate) over 2-4 hrs) - Frequent reassessment and adjust accordingly, esp when there is significant ongoing loss - If evidence of shock, give rapid infusion (over 30-60min) of 20ml/kg NS bolus, repeat if needed. In severe cases of shock, use Ringer’s Lactate solution. - Consider other causes of shock. - Admit ICU if fluid resistant shock (Not responsive after 2 NS bolus) - K+ is not routinely prescribed in IVF in the general ward. Consider oral potassium supplement in mild hypokalaemia. Significant / symptomatic hypokalaemia warrants ICU admission. 230 Section 6. Renal system Monitoring fluid status: - Clinical examination: Secretions (tears, saliva), mucosal surfaces, skin turgor, perfusion and haemodynamic status, conscious level. - Urine output , In/ out fluid balance - GI loss (vomitus/ gastric aspirates, Stool) - Body weight - Renal function (serum sodium level, urea), Base excess. - Echocardiogram for circulatory volume (LA size, IVC, Flow time constant) Some clinical scenarios may require increased or decreased fluids. In critical cases daily fluid requirement can be estimated by: Urine output (in past 24 hrs) + any fluid deficit+ On-going loss + Insensible loss (40-50mls per 100kcal expended) Increased maintenance fluid requirement: - Fever (additional 10-20%) - On-going loss (diarrhoea and/ or vomiting) - Burns, Skin infection/ inflammation (streptococcal scaled skin syndrome, Steven Johnson syndrome/ TEN) - Neonates (daily IV fluid requirements up to 150mls/Kg/day) Decreased maintenance fluid requirement: - Brain-injury/cerebral oedema (60-80% restriction) - SIADH (~ 60% restriction or guided by urine output and Na level) - Renal failure (Insensible water loss + urine output) - Heart failure (50-80% restriction) - Inactive/ bed bound (75% restriction) - Mechanical ventilated with humidified gas (75% restriction) Choice of IV fluids: Neonates: 10% dextrose + electrolyte supplements as indicated. Paediatric cases: D5 ½ NS solution: - Most cases D5 NS solution: - Hypernatraemia, Hyponatraemia/ risk of hyponatraemia Normal Saline bolus for shock Ringer’s Lactate solution in severe shock. Clinical risk of Hyponatraemia: - GE (see GE protocol) - Chronic lung disease/ bronchiolitis - Post op - CNS pathologies e.g infection, Head injury, tumour Daily Electrolyte requirements: Sodium: 2-4 mmol/Kg/day Potassium: 1-2 mmol/Kg/day (if indicated) Calcium: 0.5-1 mmol/Kg/day (if indicated) Usual preparations, to be added to IV fluids as indicated: 5.85% NaCl 1mmol Na/ml 14.9% KCl 2mmol K/ml 10% Ca Gluconate 0.22mmol Ca2+/ml 231 Section 6. Renal system Special Considerations: Hypertonic dehydration (Na >150mmol/L) - Occurs when water loss from ECF is greater than solute loss. - Common causes include: Diabetic Ketoacidosis and Diabetes Insipidus, hyperventilation, pure water loss with high fevers, and osmotic diarrhea. - Iatrogenic Causes (prolonged NPO, excessive hypertonic fluids, sodium bicarbonate, or tube feedings with inadequate water) - Aim to lower Na levels to normal (<150mmol/L) by 10 mmol/L/24h. - Rapid correction of hypernatremic dehydration can have disastrous neurological consequences, including cerebral edema and death. - Slow correction of the fluid deficit over 48 hours. Rehydration with D5/NS. - Frequent monitoring of Na levels Hyponatraemia (Na < 130mmol/L) - - - - - Consider: The patient’s fluid status (normo/hyper/ hypovolaemia). Duration and magnitude of the hyponatremia. Degree and severity of clinical symptoms Free water restriction is generally the treatment of choice for normovolemic asymptomatic hyponatremic patients. In asymptomatic hypovolemic hyponatremia, replace the fluid as well as the sodium deficit. Sodium deficit = (sodium desired - sodium actual) X volume of distribution (i.e. 0.6) X Body Weight (kg) Hypervolemic hyponatremia: Treat patients who are hypervolemic with salt and fluid restriction, plus loop diuretics, and correction of the underlying condition. In chronic, severe hyponatremia (i.e. >48hrs) sodium correction should not exceed 8mmol/L per day. In severe symptomatic hyponatremia (eg, seizures, overt neurological deficits) give hypertonic (3%) saline in 4ml/Kg bolus, preferably via central line over 15-30 mins, and recheck Na level afterwards. Repeat hypertonic saline bolus if there are persistent severe CNS symptoms attributable to hyponatraemia or until serum sodium level is above 120mmol/L. Once the CNS symptoms have abated, the sodium correction should be adjusted so that the total daily sodium correction (including the hypertonic saline) is no more that 8mmol/L in 24 hours. Monitor Na levels closely. 232 Section 6. Renal system Chapter 79 – Systemic lupus erythematosus L Leung, A Yuen Introduction: Systemic lupus erythematosus (SLE) is a chronic multisystemic inflammatory disorder of unknown etiology. The clinical manifestation is variable involving different end organs. Male to female ratio = 1 : 9 Common age of onset: 15-45 years old Prevalence: 15-52 per 100,000 in Western world Diagnosis: According to the ACR criteria: when a patient fulfills 4 or more of the 11 criteria serially or simultaneously, the diagnosis of SLE can be made with a specificity of around 95% and a sensitivity of 85% 1997 updated Criteria for Classification of Systemic Lupus Erythematosus (ACR) Criterion Definition 1. Malar rash Spare nasolabial folds 2. Discoid rash 3. Photosensitivity 4. Oral ulcers Erythematous rasied patches, keratotic scaling, follicular plugging 5. Arthritis Non-erosive arthritis involving 2 or more joints 6. Serositis 7. Renal disorder Pleuritis or pericarditis Persistent proteinuria>0.5g/day or >+++ or Cellular casts 8. Neurologic disorder Seizures or psychosis 9. Haematologic disorder Haemolytic anemia, leukopenia, lymphopenia or thrombocytopenia Oral of naspharyngeal, usually painless 10. Immunologic disorder Anti-DNA, Anti-Smith, Anti-phospholipid antibodies 11. Anti-nuclear antibody Found in more than 98% of patients with SLE, usu ≥1:640 Other criteria = SLICC 4/17 criteria Investigations: Blood: CBC, D/C, L/RFT, CaPO4, Glucose, ESR, ANA, anti-dsDNA, C3, C4 +/- CK; LDH if muscle pain, +/- troponin if chest pain To allow better assessment of risks for complications: antibodies against extractable nuclear antigens - ENA (e.g. Ro, La, Sm, nRNP), the phospholipids (e.g. anti-cardiolipin, lupus anticoagulant and anti-beta2-glycoprotein) Urine: protein, microscopy, cast CXR +/- ultrasonography to look for pericardial / pleural effusion ECG 233 Section 6. Renal system Monitoring: New symptoms (e.g. weight loss, arthritis), new skin rashes Blood pressure monitoring Fluid input / output charting and daily body weight for those with renal impairment Urinalysis with urine sediment, multistix for RBC, protein Regular monitoring of disease activity: CBC, D/C, ESR, C3, C4, CH50, anti-dsDNA, CRP (in infection, also SLE eye, pulmonary, GI, neurological activity), RLFT Treatment General: Sun-protection by physical barrier or sunscreens of SPF ≥55 blocking both UVA & B. Adequate sleep and exercise Minimise cardiovascular risk factors (blood lipids, BMI, smoking cessation, BP) Immunisations: Flu A and pneumococcal, quadrivalent HPV when stable. Vit D if on steroids. Avoiding sulphonamide-containing antibiotics and minocycline Consider contraception Non-organ threatening: Simple analgesics e.g. paracetamol and NSAID (Avoid ibuprofen due to the association of aseptic meningitis), physiotherapy for musculoskeletal complaints. Topical steroid in cutaneous lupus Antimalarials e.g. hydroxychloroquine good for musculoskeletal and skin; beneficial effect on disease activity and survival. Low dose systemic steroid (<0.35mg/kg/day) Disease modifying agents e.g. methotrexate, azathioprine if needs maintained on significant steroid dose (>0.2mg/kg/day) Serositis: A) Pleuritis OR Pericarditis Treatment: NSAID especially indomethacin Anti-malarial Low dose steroid Immunosuppressant Surgical drainage Renal disorder: Treatment: depends on WHO classification and activity / chronicity indices Steroid is first line treatment Antimalarials For Class III or IV: high dose prednisolone or IV methylprednisolone + cyclophosphamide or MMF for induction, azathioprine or MMF for maintenance. For Class V: may not respond to steroid, Cyclosporin A, MMF may be useful Other drugs for severe refractory nephritis: Tacrolimus, Rituximab 234 Section 6. Renal system Chapter 80 – Postnatal management of antenatally diagnosed hydronephrosis PH Chan, L Leung Working definition of antenatally diagnosed hydronephrosis (ANH) All neonates whose antenatal ultrasound scans show: - Anterior-posterior diameter (APD) of renal pelvis ≥ 4mm at 2nd trimester and/or ≥7mm at 3rd trimester. AN USG findings, in conjunction with ANH that point to significant urinary tract obstruction (please refer to Fig. 2) - Oligohydramnios - Abnormal bladder (thickened wall, ureterocele) - Bilateral renal tract dilatation with APD >15mm - Solitary kidney with APD >15mm Tips on initial management - Routine urinalysis or urine culture is NOT needed for all neonates with ANH. - Observation in SCBU (urine output, blood pressure and RFT at 48 hours) is recommended only for neonates who have AN USG findings that indicate significant urinary tract obstruction (see above and Figure 2). Renal team should be notified in such situations. - For those who do not require admission, investigation and follow-up can be arranged in postnatal (PN) ward (Figure 1), trimethoprim (TMP) prophylaxis can be started on discharge from PN ward. - Dose of trimethoprim: 1-2mg/kg PO nocte - Parents should be warned of symptoms of UTI and instructed to seek early medical attention. Timing of and preparing request for investigations - PN USG should be done >72hrs of age in well-hydrated baby. - Liaise with radiologist for arrangement of investigations that need to be done within 1 month - Specify clearly in request form AN USG finding and time frame of investigation - MAG3 should preferably be done after 6 weeks to allow for renal maturation Role of MCUG in evaluation of ANH is controversial - Neither the grade of dilatation nor gender is a predictive factor for VUR in ANH. - The clinical relevance/ benefit of identifying VUR (especially of low grade) in infants who have not had any UTI is unknown. - Indications are controversial. It is advised when USG identifies ureteric dilatation, as per algorithm in Figures 1 and 2, and whenever there is UTI associated with HN. Consult renal team at any stage in the presence of Any complications (like UTI, gross haematuria, voiding abnormalities) Any unusual radiographic features (like thickened bladder) Any queries 235 Section 6. Renal system Figure 1. Algorithm of management of unilateral ANH with no feature of significant obstruction Antenatal ultrasound finding APD <10mm APD 10-15mm APD >15mm Book early renal USG (within 4-8weeks) Start trimethoprim Book early renal USG (within 3 months) Admit SCBU Book early renal USG (within 2-4 weeks) Start trimethoprim Postnatal ultrasound finding Ureteric dilatation With any degree of HN Start TMP if not yet done Book MCUG and MAG3 scan Refer renal clinic Yes No Bilateral HN with APD ≥ 10mm bilaterally Start TMP if not yet done Book MCUG within a week Follow Fig. 2 from broken line-bordered box Yes No APD >15mm or Calyceal dilatation with any degree of HN No No Yes Start TMP No APD < 6mm APD 6-9.9mm APD 10-15mm If USG done beyond 1m: Off TMP & Close case If USG done beyond 1m: Off TMP Close case after 1yr if no complications like UTI Repeat renal USG 3 and 6-9m after 1st USG If USG done within 1m: Off TMP Repeat USG 3-6m later Repeated USG (if needed) HN static or improved If USG done within 1m: Off TMP Repeat USG 3-6m later MAG3 scan No obstruction AND relative renal function >40% for both kidneys Obstruction or a kidney with relative renal function ≤40% MCUG APD >10mm persists beyond 1 year VUR grade III or above Book MAG3 Book DMSA Refer renal clinic Close case 236 VUR grade II or below Section 6. Renal system Figure 2. Algorithm of management of bilateral ANH/ ANH in solitary kidney/ ANH with features of significant obstruction Antenatal ultrasound finding HN with ureteric dilatation or HN with oligohydramnios or HN in solitary kidney APD ≥10mm or HN with APD ≥10mm bilaterally or HN with abnormal bladder No Yes Maximal APD 6 to 15mm Ix and Mx according to unilateral ANH Follow Fig. 1 from the start according to maximal APD Maximal APD >15mm Admit SCBU for monitoring Book renal USG and MCUG >72hrs to within 1 week Start trimethoprim Admit SCBU for monitoring Book renal USG and MCUG within 3 days Start trimethoprim Postnatal Ix result Suggestive of PUV, PUJO, VUJO, duplex kidneys, ureterocele or other structural anomalies Yes Liaise with renal team & refer to urology No USG normal or APD <10mm with no calyceal/ ureteric dilatation Yes MCUG result No USG APD ≥10mm or calyceal/ ureteric dilatation MCUG result VUR Grade III or above VUR Grade II or below Book MAG3 & DMSA Book MAG3 scan VUR Grade II or below VUR Grade III or above Repeat USG at 3 months and follow Fig. 1 starting from double-bordered box using maximal APD as a guide No need to repeat MCUG Book DMSA scan Refer renal clinic 237 Section 6. Renal system Chapter 81 – Systemic corticosteroids therapy E Ho, YY Lam, L Leung Relative potencies and equivalent doses of corticosteroid: Dosage of corticosteroids varies widely depending on the disease states, and their relative glucocorticoid and mineralocorticoid activity should be considered when deciding the appropriate treatment. The comparison table below summarises the relative potencies and administration precautions: Equivalent Glucocorticoid Mineralocorticoid dose potency potency Betamethasone (inj disod phosphate) Dexamethasone (inj Na phosphate) 0.15 mg 0.15 mg No significant Fludrocortisone tab anti-inflamma tory effect Hydrocortisone (inj succinate) Methylprednisolone (inj succinate)* Prednisolone tab Administration Half-life (hours) 0 Inj (suspension): not for IV 36-54 25 – 30 0 PO: with food Inj: IV push if < 10 mg; high dose should be given as infusion over 15-30 minutes 36-54 10 125 PO: with food No inj available 18-36 25 4 mg 1 2 0.8 mg 5 0 1 mg 4 1 238 PO: with food Inj: bolus – dilute to 50 mg/ml and give over 3-5 minutes Infusion – dilute to 1 mg/ml and give over 20-30 minutes Inj: ≤ 1.8 mg/kg or ≤ 125 mg/dose, IV push over 3-15 minutes ≥ 2 mg/kg or 250 mg/dose, IV push over 15-30 minutes > 15 mg/kg or ≥ 1 g/dose, infuse over 1 hour* PO: with food 8-12 18-36 18-36 Section 6. Renal system Special aspects in corticosteroid administration: * Association of high dose IV methylprednisolone and cardiac toxicities have been reported : 1. Hypotension, bradycardia and asystole after high-dose IV methylprednisolone 2. Recurrent cardiocirculatory arrest after kidney transplantation 3. Avoid long line administration of IV methylpredisolone. Although the exact mechanism is not known, rapid infusion and underlying cardiac conditions were considered important factors. Ca and Vit D supplement Many guidelines in adults suggest adding Ca and vitamin D if > 3 months steroids and ≥ 5 mg prednisolone a day, though negative bone effects have been found even at 2.5 mg daily. Adults: Calcium 1500 mg/day (diet + supplement) or 1000 mg/day supplement Vit D: 400-500 IU/day in < 65 years, 800-1000 IU/day in older Activated vit D (calcitriol or alfacalcidol) more effective than vit D but need greater monitoring for hypercalciuria or hypercalcemia Some suggest if > 3 months: add biphosphonate, but avoid in those who wish to conceive Children: no specific recommendations beyond 1996 American College of Rheumatology guideline. consistently ingest, through either diet or supplements, the following daily calcium intake: 800 mg/day at ages 1-5 years, 1,200 mg/day at ages 6-10 years, and 1,500 mg/day at ages 11-24 years. at least 400 IU/day of vitamin D may use activated vitamin D such as calcitriol 0.25 mcg daily but need to monitor for hypercalciuria and hypercalcaemia KWH Ca preparation CaCO3 1 g tab Calcium lactate 300 mg tab CaCl2 10% inj Calcium gluconate 10% inj “Calperos D3” tab Elemental Ca2+ content 10 mmol or 400 mg 1 mmol or 39 mg 0.68 mmol or 27.3 mg Ca2+ ml 0.22 mmol or 9 mg Ca2+ / ml Ca 500 mg + Vit D 400 IU Corticosteroid treatment and weaning: Physiological replacement dose: - hydrocortisone: 6-8 mg/m2/day q6h IVI/IMI - methylprednisolone 2 mg/m2/day q6-8h IVI - hydrocortisone 8-12 mg/m2/day PO tds - predisolone 2-3 mg/m2/day PO bid - dexamethasone 0.2-0.3 mg/m2/day PO QD 239 Section 6. Renal system Stress Dose Replacement: - IM/IV if vomiting or diarrhoea - Minor stress (fever, minor infection) Double to triple i.e. 2-3x physiological replacement dose - Major stress (surgery, major infection, trauma) Load with 50mg/m2 IV/IM Hydrocortisone, followed by 5-6x replacement dose at around 100 mg/m2/day Q6H Mineralocorticoid dose: Fludrocortisone: 0.1-0.2 mg/m2/day daily to BD dose Infants with mineralocorticoid deficiency may also need salt supplement, usual dose around NaCl 1 gram/day Children on stress dose of hydrocortisone also have mineralocorticoid activity (40 mg hydrocortisone equivalent to 0.1 mg fludrocortisone) Empirical method for weaning high dose steroid: 1. High dose steroid for 1-4 weeks, cut by 25% every 4 to 7 days 2. High dose steroid for > 1 month, wean first stepwise to stress dose, then cut by 10-25% every 1 to 2 weeks 3. With long weaning schedule, can give all dose once in the morning or alternate day to allow HPA axis to activate and minimise growth retarding effect Test for suppression: 1. Morning cortisol 24 hours after last dose of corticosteroid can be used as a screening test for basal secretion (not stress response), level usually ≥ 200 nmol/L 2. Low dose synacthen test: test whether adrenal can respond to stress signal of pituitary. Pituitary-adrenal axis is the last to recover; if this test is passed, the axis is not suppressed. Dose of synacthen used is 1 mcg/m2 IVI. Cortisol level at baseline, 20 minutes, 30 minutes and 60 minutes. Peak level should be > 500 nmol/L. 240 Section 6. Renal system Chapter 82 - Intravenous cyclophosphamide L Leung Protective isolation (Place patient in a single room is preferable) DAT Renal chart ARRR Q4H Strict Chart I/O Urine Q8H for SG, ketone (aim: keep SG < 1.010), RBC, start 1 hour after IV fluid infusion Save urine for inspection. Inform if gross haematuria, urine SG > 1.020, ketone ++ Blood for CBP D/C, ESR, L/RFT, CaPO4, glucose, C3, ANA, Anti-ds DNA 1. 2. 3. 4. IV fluid start infusion 1 hour before CYP: 1/2 saline + 5% dextrose _________ ml/hour (~ 2 L/m2/day) * IV Cyclophosphamide ___________ mg in 150 ml NS over 1 hour ** IV Mesna _________ mg in 50 ml Normal Saline (20% of total CYP dose) for 4 doses at 0, 3, 6, 9 hours of CYP infusion IV Ondansetron 0.15 mg/kg (adults 4-8 mg) in 50 ml Normal Saline for 4 doses at 0, 4, 8, 12 hours of CYP infusion. Encourage fluid intake and frequent bladder emptying. FU ________ in 2/52 and check CBP D/C *Fluid: adult 125 ml/hour for a total of 3 L; Our patient – iv fluid at 125 ml/hr for > 8 hours, follow with comparable rates of oral fluid for 24 hours. If greater than 0.5 litre positive balance, diuretics is indicated. For those who have oliguria or difficulty voiding, may insert 3-way Foley catheter (minimum size Fr14) with continuous bladder flushing with standard irrigating solution for 24 hours (adult 3L) **Cyclophosphamide: If CrCl < 40 ml/min, initial dose at 0.5 g/m2 If CrCl > 40 ml/min, initial dose at 0.75 g/m2 Follow up doses determined by WBC nadir (10-14 days) of previous dose: < 1500/mm3, reduce dose by 0.25 g/m2 Repeat dose monthly for 6 months induction therapy Maintenance therapy may be considered, q 3 months for 2 years Contraindications: Pregnancy (screen with urine pregnancy test before each dose if indicated) Breast feeding, active or chronic infection, history of malignancy 241 Section 6. Renal system Chapter 83 - Formulae related to Nephrology L Leung Total body water = 80% body weight (Preterm) 70% (term) 65% (toddler / children) 60% post-pubertal male 50% post-pubertal female TBW deficit = 0.6 × premorbid weight (kg) × (1 - 140/Se Na+mmol/L) Free water deficit = TBW × (Na+/140 – 1) for hypernatremia Na deficit = TBW × (Desired [Na] - Plasma [Na]) where TBW (Total Body Water) in adults = 0.6 (men) or 0.5 (women) × Body weight (kg) 0.8 in premature infants, 0.7-0.75 in term infants, 0.65-0.7 in toddler, 0.6 after puberty. Since fat has much lower water cantaint than muscle, TBW as %BW is lower with increasing obesity. Prerenal FENa Neo<2% Child ≤ 1% Adult <1% Prerenal Ur Na Neo <10mmol/l Child <10 Adult <20 Renal FENa Neo >2% Child >3% Adult >3% Renal Ur Na Neo >40mmol/l Child Adult >25 Calculating true Na in Pseudohyponatremia due to hyperglycaemia: Expect a 1.4 mmol/L fall in Na for every 5.5mmol/L (100mg/dL) rise in BSL. Na falls 1mmol/dL with a 4 mmol/L rise in BSL. Serum osmolality formula (LeFever Kee) 2x serum Na + urea (mmol/l) + glucose (mmol/l) = Se Osmo (mOsm/kg), normal = 280-295 In DKA, effective Plasma osmolality = 2x serum Na + glucose (mmol/l) as urea freely diffusible and not cause major intracellular volume changes. Hypokalemia 24 hr urine K Urine [K]* Urine K/Cr mmol/mmol Urine Na:K K conserve Adults <30mmol/day <15mmol/l <1.5 >1 Urine K loss >30 mmol/day >15mmol/l >1.5 <1 Note: Random [K] measurements not accurate if urine sodium is < 30 meq/L and/or urine osmolality is lower than the plasma osmolality since urine [K] is determined by both the amount of potassium in urine and urine volume. Acidosis lead to hyperK from redistribution: decrease pH 0.1 will increase K by 0.7meq/L. Phosphate handling % tubular reabsorption of phosphate (TRP) Tubular Reabsorption of PO4 is 80-90% (Feld: 80- 97%) in normal circumstances in >6 mths old. TRPi (%) = ( 1- FEPi) = 1 – Upi x PCr x 100 UCr x P pi NB. Blood PO4 should be taken at time of urine collection. Hyperphosphatemia: expect TRP <70% (increased PO4 excretion) Hypophosphatemia: expect TRP >95% (some say >80%) (decreased PO4 excretion) 242 Section 6. Renal system Maximum tubular reabsorption of PO4 per unit volume of GFR (TmPi/GFR) TRPi is markedly influenced by changes in GFR as well as dietary PO4 intake. More reliable measure of overall tubular reabsorptive capacity = TmPi/GFR. This is because in severe hypophosphatemia or decreased GFR, filtered load may be so low that TRP is within normal range. This is derived either by Walton-Bijvoet nomogram or by Brodehl formula (found to be satisfactory in spot specimens, no need fasting) TmPi/ GFR = Ppi - Upi x PCr UCr In Hypophosphatemic patient, High TmPi indicates an appropriate renal response to hypophosphatemia which is usually due to gastrointestinal loss or intracellular shift. Low TmPi indicates increased renal excretion secondary to primary or secondary hyperPTH, Fanconi syndrome, X LH, autosomal dominant hypophosphatemic rickets or oncogenic osteomalacia. TMPi/GFR <3 months: 1.02-2mmol/L 3-12months: 1.13-1.88mmol/L 1-15yrs: 0.9-1.7mmol/L mmol/L mg/100ml mmol/L 243 mg/100ml Section 6. Renal system Renal threshold phosphate concentration (TmPO4/GFR), serum phosphate, and other indices of renal handling of phosphate at different ages (K Kruse et al, 1982). Index TmPO4/GFR (mg/100 ml GF) TRP (%) Age (years) 6-6.9 7-7.9 8-8.9 9-9.9 10-10.9 11-11.9 12-12.9 13-13.9 14-14.9 15-15.9 16-16.9 17-17.9 20-40 6-6.9 7-7.9 8-8.9 9-9.9 10-10.9 11-11.9 12-12.9 13-13.9 14-14.9 15-15.9 16-16.9 17-17.9 20-40 Girls n 9 27 29 29 19 27 28 31 26 22 33 11 12 9 27 29 29 19 27 28 31 26 22 33 11 12 Median 6.00 6.50 6.00 6.10 5.70 5.70 5.67 5.58 4.60 4.45 3.45 4.17 3.87 92.4 95.5 93.4 94.2 94.7 92.9 93.7 94.6 92.9 93.2 91.0 90.5 89.5 Mean 5.71 6.40 6.02 6.07 5.84 5.71 5.50 5.50 4.61 4.59 4.07 3.99 3.55 91.2 94.7 93.5 93.6 93.4 92.8 93.2 93.1 93.0 92.1 89.8 89.9 89.9 Boys SD 0.85 0.83 0.81 0.83 0.94 1.08 0.88 0.88 0.69 0.83 0.66 0.51 0.66 3.86 2.68 2.26 2.69 2.66 4.46 4.67 4.46 3.01 3.17 3.60 3.50 4.30 Range 4.50-6.90 4.70-8.00 4.30-7.70 4.70-7.40 4.40-7.70 3.94-8.20 3.42-7.30 3.30-7.25 3.41-6.25 3.25-6.41 2.48-5.10 3.18-4.57 2.58-4.85 83.9-95.8 89.0-98.1 85.7-97.5 83.5-97.2 88.7-97.9 79.9-97.9 76.2-97.7 81.1-98.5 86.8-98.3 85.7-97.5 82.3-95.8 82.7-95.3 80.7-96.1 n 15 33 25 20 27 31 36 29 19 10 15 13 12 15 33 25 20 27 31 36 29 19 10 15 13 12 Median 6.40 5.80 5.80 6.15 6.10 5.25 5.51 5.85 5.40 4.70 4.23 4.13 3.54 94.5 93.8 93.6 94.0 94.4 93.4 94.9 95.4 94.0 90.6 90.5 89.3 89.3 Mean 6.25 5.85 5.97 5.96 5.89 5.21 5.47 5.89 5.39 4.69 4.37 4.27 3.21 94.1 93.4 93.8 94.1 93.4 92.4 93.1 94.7 92.6 91.4 90.0 90.5 87.8 SD 0.89 0.74 0.66 0.94 0.96 0.72 0.80 0.78 0.94 0.72 0.66 0.66 0.78 2.68 1.86 2.01 2.64 3.78 2.96 4.89 2.41 4.29 2.94 3.75 3.10 5.00 Range 4.80-8.00 4.50-7.00 4.90-7.10 4.20-7.80 4.07-7.50 3.88-6.60 3.70-6.92 4.27-7.47 2.58-7.05 3.60-5.90 3.47-5.88 3.33-5.90 2.05-4.28 86.8-98.1 88.3-98.1 90.7-98.4 88.5-98.1 82.1-99.3 85.9-96.7 79.6-98.6 88.1-98.7 80.2-98.4 88.2-95.7 83.8-96.4 85.8-94.8 81.3-95.5 Increased FE Mg (urine Mg x Se Cr / Se Mg x Ur Cr normal range from Conti 2009 is 0.5-4%) Aminoaciduria % tubular reabsorption (Taa) = 1- [ Uaa / Paa] x 100% Ucr / Pcr Taa for most amino acid is >98%, except for glycine (95%) and histidine (92%) Serum anion gap = Na − (Cl + HCO3). Normal 12-14mEq/L Urine anion gap = Na + K - Cl, negative in normal during acidosis, 0 or positive in RTA does not correlate will with urinary NH4+excretion in neonates or infants in first few weeks of life. Bladder size: < 2 yrs: (2x age +2) oz > 2 yrs: (age/2 +6) oz 244 Section 6. Renal system Chapter 84- Normal Urine Values L Leung < 4mg/kg/24hrs or 0.10 mmol/kg/24hrs 24 hr calcium* # nd Ca/Cr in 2 void urine(Laufer 1989 in Paed r/v 2001 RTA article by J Chan) adults < 0.21 mg/mg or 0.7 mmol/mmol ………………………………19mth to 6 yr < 0.41 mg/mg (not as accurate as 24 hr Ca) 7-18 mth < 0.60 mg/mg < 7 mth <0.86 mg/mg In hypocalcemia, a urine Ca/Cr of > 0.3 mmol/mmol on spot samples suggests inappropriate excretion (Yamamoto 2000) Ca/Cr <0.2 mmol/mmol (some quote <0.1 Hypocalciuria mmol/mmol) or <0.5mg/day Creatinine# (indicator for adequate urine collection) newborns 8-10mg/kg/24 hr 10-12mg/kg/24 hr children Adult females 12-15mg/kg/24 hr 15-20mg/kg/24 hr Adult males <50mg/1.73m2/24hr (or<2mg/kg/24hr) Oxalate# 0.46mmol/1.73m2/24hr 1-5yrs: <0.12mmol/mmol(0.08mg/mg) Oxalate/Cr Graph ^ <815mg/1.73m2/24hr (35mg/kg/24hr) Uric acid# <75mg/g Cr Cystine# >180mg/g Cr Citrate# Male: >1.9mmol(365mg)/1.73m2 Female: >1.6mmol(310mg)/1.73m2 Manna: hypocitraturia= girls <300mg citrate/g Cr Boys<125 urine uric acid(mg/dL) x plasma Cr (mg/dL):urine Cr Hyperuricosuria (mg/dL) > 0.53mg/dL of GFR(La Manna 2001@) FE potassium 14.5 ±8.9% <5% FEmagnesium TMP/GFR Threshold for maximum PO4 reabsorption:PlPO4 – [(UrPO4/UrCr) x Pl Cr] <3 months: 1.02-2mmol/L 3-12months: 1.13-1.88mmol/L 1-15yrs: 0.9-1.7mmol/L *Noncalculous symptomatic Idiopathic Hypercalciuria reported in association with micro and gross haematuria, recurrent abdo pain or flank pain, urine incontinence, dysuria, urgency-frequency syndrome, mild proteinuria, recurrent UTI, in addition to renal stones (Vachvanichsanong Scand J U”rol Nephrol 2000) # from Laufer J. Urolithiasis in children: current medical management. Pediatr Nephrol 1989;3:317-331; Sargent JD. Normal values for random urinary calcium to creatinine ratios in infancy. J Pediatr 1993;123:393-397; and Manz F. Urinary calcium excretion in healthy children and adolescents. Pediatr Nephrol 1999;13: 894-899; Pediatr Nephrol 2010;25:403-413 @ Stapleton FB, A screening test for hyperuricosuria. J Pedatr 1983;102:88-90 245 Section 6. Renal system ^ Urine Oxalate/ Cr ratio Normal values for spot urine samples: creatinine ratios (solute/creatinine). Ratios are more prone to error than are timed samples. Interpret with respect to daytime, relation to meals, diet, medication, age and regional differences [5, 6, 36–41] (Ca calcium, RTA renal tubular acidosis) Bernd Hoppe et al, Pediatr Nephrol (2010) 25:403–413 Parameter age Calcium <12 months 1–3 years 1–5 years 5–7 years >7 years Oxalate 0–6 months 7–24 months 2−5 years 5−14 years >16 years Citrate 0–5 years >5 years Magnesium Uric acid >2 years Ratio of solute to creatinine mol/mol mg/mg <2 0.81 <1.5 0.53 <1.1 0.39 <0.8 0.28 <0.6 0.21 mmol/mol mg/g <325–360 288–260 <132−174 110−139 <98−101 80 <70−82 60−65 <40 32 mol/mol g/g >0.25 0.42 >0.15 0.25 mol/mol g/g >0.63 > 0.13 <0.56 mg/dl (33 µmol/l) per GFR (ratio × plasma creatinine) Remarks Highest Ca excretion with breast milk feeding, ratio increasing after meals (up to 40%), by loop diuretics, immobilization and steroids Primary hyperoxaluria types I/II for constant excessive elevation, check also urinary glycolate, L-glycerate and plasma oxalate. Secondary hyperoxaluria: determine intestinal oxalate absorption and stool Oxalobacter formigenes colonization Low with tubular dysfunction: RTA, prematurity, hypokalemia, renal transplantation For <2 years, no reliable data Higher than in adults throughout childhood; no reliable data for age <2 years 246 Section 7. Endocrinology, growth & nutrition Section 7: Endocrinology, Growth & Nutrition 247 Section 7. Endocrinology, growth & nutrition Chapter 85 - Nutritional assessment in children YY Lam Purpose of nutritional assessment: To define state of nutritional well being by assessing the body composition and size of metabolic active mass Methods of Nutritional Assessment: Anthropometry Calorimetry and prediction formula Biochemistry Anthropometry Measures: - *Weight - *Height: Stadiometer Head position: Frankfurt plane – defined by a line joining the superior border of tragus to the most inferior point of infra-orbital rim Pressure on mastoid process - Arm span - *Weight for height (> 120% = overweight, < 80% = wasting) - *BMI (> 90% = overweight, > 97% = obesity) - *Skinfold thickness (optimal > 10% and < 90%) of triceps and subscapular skinfold - *Bioimpedance Assess body composition by the measurement of resistance and reactance when a weak electric current is passed through the body - Mid-arm circumference (MAC) index of muscle mass midpoint of upper arm (non-dominant arm) Mid arm muscle circumference (MAMC) MAMC = MAC in cm–(3.14 x Triceps skinfold in cm) - Waist circumference measured midway between lower rib margin and iliac crest laterally - Hip circumference measured horizontally over the trochanter region *Standard charts available Indirect Calorimetry: - measurement of the heat of metabolism (energy output) via oxygen consumption (VO2) and carbon dioxide production (VCO2) - BMR (basal metabolic rate) - minimum energy to sustain the organism; carried out in early morning within 30 minutes upon wakening, 12 to 18 hours after ingestion of food, in complete muscular rest and a comfortable environment - REE (resting energy expenditure) - around 10% > BMR, taken anytime of the day, at least 2 hours after meal, in a resting state for at least 30 minutes and have no skeletal movement during the rest - TEE (total energy expenditure) - the sum of energy expenditure during sleep, rest, thermogenesis and physical activity 248 Section 7. Endocrinology, growth & nutrition Measurement of Energy Expenditure (EE) by IC WEIR’s equation: EE = [3.941 (VO2) + 1.106 (VCO2)] 1.44 – (2.17 UN) or WEIR’s abbreviated equation: EE = [3.9 (VO2) + 1.1 (VCO2)] 1.44 EE: energy expenditure (kcal/day) VO2: oxygen uptake in ml/min VCO2: carbon dioxide produced in ml/min UN: total urea nitrogen (N) in gram/day Utilization of REE for Nutritional goal (Repletion, Depletion or Maintenance) 110% REE for weight reduction, 130% REE for maintenance and 150% for weight gain Biochemical and immune markers for nutritional assessment (indicators for protein status) 1) Albumin T1/2: 18-20 days, but significant drop can occur in < 7 days in patients under stress with catabolic state 21-27 g/L = Moderate malnutrition <21 g/L = Severe malnutrition 2) Total iron binding capacity (TIBC) TIBC < 200 mcg/dL (x 0.179 µmol/L) indicative of malnutrition 3) Transferrin T1/2: 8-10 days, serum transferrin (mg/dL) = (0.68 x TIBC) + 21 100-150 mg/dL = Moderate malnutrition < 100 mg/dL = Severe malnutrition 4) Prealbumin (T1/2: 2-3 days), Retinol-binding protein (T1/2: 12 hours) and IGF-1 (T1/2: 2-6 hours) may reflect acute decrease better 5) Nitrogen (N) balance - Around zero in healthy adults, N output estimated from 24-hour total urine nitrogen - Urinary [N] output in grams = (urea in mmol / 24hours) / 1,000 × 28 - Total daily [N] output = Urinary [N] output + 2g (estimated loss from stool + skin) - Nitrogen intake: dietary intake of protein, 1 gram protein = 0.168 g Nitrogen - Nitrogen balance = [N] intake – [N] output - A positive 3 to 5 grams per day nitrogen balance is desired to promote anabolism and wound healing 249 Section 7. Endocrinology, growth & nutrition Chapter 86 - Management of obesity YY Lam Definition of obesity: - Obesity: excessive accumulation of fat in adipose tissue to the extent that health may be impaired (WHO 2000) - Hong Kong data: BMI > 90% = overweight; BMI > 97% = obesity Parameters measured to reflect degree of obesity: - Wt, Ht, BMI, % of Wt for Ht, waist and hip circumference, Fat % (BIA) Investigations required for obesity: - Rule out underlying pathology if pathological obesity suspected (hypothyroidism, Cushing syn, dysmorphic syndromes etc) - Look for obesity related complication (hyperlipidaemia, DM, OSAS, HT etc) BP, TSH, FBS, fasting cholesterol (LDL-C, HDL-C), fasting triglyceride Abnormal glucose/strong family history of DM Suspected DM: OGTT, Hb Alc Check for habitual snoring, enlarged tonsils: PSG Orthopaedic complication Hirsutism, abnormal menstruation (PCOS) Abnormal LFT, abdominal pain: USG to rule out steatohepatitis and gallstone Management of Obesity (multidisciplinary): - < 7 years, weight maintenance as a goal unless with complication - ≥ 7 years, weight reduction diet usually 1,000-1,500 kcal/day (< 1,000 kcal not advisable) - Weight loss of 0.5-1 kg/month is well tolerated - Indirect calorimetry may help to establish energy requirement, ≤ 110% REE for weight reduction - Set a practical and achievable goal; seek support from family - Empathetic and supportive to patients - Regular weighing to keep track of weight changes - Identify unhealthy habits and modify behaviour e.g. reduction of TV watching / computer playing time to < 2 hours/day - Diet advice: food diary for self monitoring, education on food labeling and caloric content of food (a can of soft drink/day = 1 lb of weight/month) Exercise: increase activity, decrease sedentary habits, prescribe around 200-300 kcal exercise/day 250 Section 7. Endocrinology, growth & nutrition Chapter 87 - Diabetic ketoacidosis YY Lam Definition of DKA: hyperglycaemia (> 11 mmol/L) venous pH < 7.3 and/or bicarbonate < 15 mmol/L mild pH < 7.3; HCO3 < 15 mmol/L moderate pH < 7.2; HCO3 < 10 mmol/L severe pH < 7.1; HCO3 < 5 mmol/L associated with glycosuria, ketonuria and ketonaemia Causes of DKA: - undiagnosed type 1 DM (TIDM) - insulin omission or manipulation, insulin pump failure - inadequate insulin during periods that increase needs (illness, infection, stress, puberty, pregnancy) Signs and symptoms of DKA: Polyuria, polydipsia, dehydration, weight loss, lethargy, nausea, vomiting, abdominal pain, fruity smelling breath, flushed face, confusion, hyperventilation and Kussmaul breathing Morbidity and mortality of DKA: - mortality from 0.15% to 0.31%, cerebral oedema accounts for 57-87% of all DKA deaths - incidence of cerebral oedema from 0.46% to 0.87% - reported mortality rates from cerebral oedema from 21% to 24% - significant morbidity evident in 10-26% of survivors after DKA and cerebral oedema Presentation of cerebral oedema: It typically occurs 4 to 12 hours after treatment. Symptoms and signs are variable and include headache, gradual deterioration in level of consciousness, inappropriate slowing of the pulse rate, and increase in BP Management of DKA: - Mild DKA without vomiting and dehydration may be managed at home in established DM with well trained parents, close monitoring of glucose level and frequent evaluation are needed - For severe DKA, need admission and close monitoring Management after hospital admission: - Use admission BW for calculation in fluid management (for severe obesity, fluid calculation may need to be adjusted to avoid overhydration) - Hourly HR, RR, BP - Strict I/O - Airway management, catheterize bladder, NG tube if impaired consciousness - Good venous access (can serve as blood taking access) - ECG monitor for hyper or hypo K - D’stix hourly, monitor urine sugar and ketone - Electrolytes, urea, Hct, blood sugar level (BSL), blood gas 2 to 4 hourly - Close neuro-observation (hourly or more frequent) - Principles of fluid and electrolyte management: 251 Section 7. Endocrinology, growth & nutrition - - - Restore circulating volume Correct electrolyte, fluid deficit Restore GFR for glucose and ketones clearance Avoid large fluid boluses and rapid infusion N.S bolus only if in shock, 10-20 ml/kg over 1-2 hours NaHCO3 not recommended Deficit replaced slowly over at least 48 hours (fluid regime as per British Columbia Children’s Hospital protocol) Corrected Na level by adding 0.3 mmol/L Na for every 1 mmol/L glucose above 5 mmol/L [True Na = measured Na + 0.3 x (BSL – 5)] NS as initial fluid for 4 to 6 hours, subsequent fluid tonicity ≥ 0.45 NS (consider 0.45% NaCl if serum Na ≤ 145 mmol/L) Add K 40 mmol/L fluid if +ve urine output Start insulin infusion 0.05-0.1 unit/kg/hour (included in total fluid calculation) Follow instruction of preparing solution A, B, C (see table and diagram) Start IV glucose when BSL ≤ 17mmol/L or glucose drop > 5 mmol/L/hour, adjust rate of solution A and B to give fluid with NS or 1/2 NS with various glucose concentration (see table and diagram) Keep BSL > 15 in first 24 hours, avoid rapid drop, aim < 5 mmol/L/hour Na usually rises with fall of glucose, unexpected drop of Na may be sign of overhydration and potential cerebral edema, keep highish effective osmolality [2 x (Na + K) + plasma glucose] and avoid rapid drop Total fluid per day seldom exceeds 1.5-2x normal daily maintainence Consider PO4 supplement for deficiency or to avoid hyperchloridaemia; closely monitor Ca2+ level if PO4 given Management of cerebral oedema: Keep head elevated Rate of fluid administration reduced by around one third IV mannitol (0.25–1.0 g/kg over 20 minutes) in patients with signs of cerebral oedema before impending respiratory failure; repeat in 2 hours if no initial response Hypertonic saline (3%) 5-10 mL/kg over 30 minutes may be an alternative to mannitol Intubation and ventilation if necessary. Brain imaging only when patient is stable. Introduction of oral feeding and change to subcutaneous insulin: - oral fluid introduced with clinical improvement and DKA corrected - reduce IVF if oral intake tolerated - discuss with endocrinologist for dose and regime of subcutaneous insulin; first dose usually starts before a meal - allow 1 hour after short acting insulin before stopping IV insulin infusion. Reference: http://endodiab.bcchildrens.ca/pdf/dkaprt.htm 252 Section 7. Endocrinology, growth & nutrition Solution A and solution B preparation 1) For NaCl 0.45% / Dextrose solution with K 40mmol/L (when blood glucose ≤ 17 mmol/L or glucose drop > 5 mmol/L/hour) Solution A (per 1,000ml) – NaCl 0.45% + 40 mmol KCl Solution B (per 1,000ml) – NaCl 0.44% / Dext 12.46% + 39.2 mmol KCl To prepare the above solutions using the IV fluids and electrolytes available in KWH: Ingredients Solution A Solution B NaCl 0.9% 250 ml ----NaCl 23.4% ----9.6 ml KCl 14.9% (2 mmol K+/ml) 10 ml 10 ml Water for Injection 240 ml Dextrose 5% ----230 ml Dextrose 20% ----260 ml Final volume 500 ml 509.6 ml Final osmolarity 234 mOsm/L 920 mOsm/L 2) For NaCl 0.9% / Dextrose solution with K 40 mmol/L (when blood glucose ≤ 17 mmol/L or glucose drop > 5 mmol/L/hour) Solution A (per 1,000 ml) – NaCl 0.88% + 40 mmol KCl Solution B (per 1,000 ml) - NS / Dextrose 12.5% + 40 mmol KCl To prepare the above solutions using the IV fluids and electrolytes available in KWH: Ingredients Solution A Solution B NaCl 0.9% 490 ml ----NaCl 23.4% ----19.2 ml + KCl 14.9% (2 mmol K /ml) 10 ml 10 ml Dextrose 10% ----432 ml Dextrose 50% ----39 ml Final volume 500 ml 500.2 ml Final osmolarity 381.6 mOsm/L 1081.3 mOsm/L Solution A: NS or 1/2 NS solution with K Solution B: NS/D12.5 or 1/2 NS/D12.5 with K Solution C: Insulin Infusion 253 Section 7. Endocrinology, growth & nutrition Chapter 88 – Normal values YY Lam Bone age interpretation (Ref : Radiographic Atlas of Skeletal Development of the Hand and Wrist by Greulich WW and Pyle S1): Normal bone age should fall within the range defined by the chronological age +/- 2 SD The variability of skeletal age of girls in the Brush Foundation study Skeletal Age (in months) Chronological Age Standard Deviation 3 months 6 months 9 months 12 months 18 months 0.72 1.16 1.36 1.77 3.49 2 years 2 1/2 years 3 years 3 1/2 years 4 years 4.64 5.37 5.97 7.48 8.98 4 1/2 years 5 years 6 years 7 years 8 years 10.73 11.65 10.23 9.64 10.23 9 years 10 years 11 years 12 years 13 years 10.74 11.73 11.94 10.24 10.67 14 years 15 years 16 years 11.30 9.23 7.31 254 Section 7. Endocrinology, growth & nutrition The variability of skeletal age of boys in the Brush Foundation study Skeletal Age (in months) Chronological Age Standard Deviation 3 months 6 months 9 months 12 months 18 months 0.69 1.13 1.43 1.97 3.52 2 years 2 1/2 years 3 years 3 1/2 years 4 years 3.92 4.52 5.08 5.40 6.66 4 1/2 years 5 years 6 years 7 years 8 years 8.36 8.79 9.17 8.91 9.10 9 years 10 years 11 years 12 years 13 years 9.00 9.79 10.09 10.38 10.44 14 years 15 years 16 years 17 years 10.72 11.32 12.86 13.05 Fasting blood glucose and OGTT interpretation: Fasting blood glucose: < 6 mmol/L = normal 6.1 to 7 mmol/L= impaired fasting glucose ≥ 7 mmol/L = suspicious of diabetes mellitus OGTT Test: glucose load = 1.75 gram/kg (maximun 75 grams), Unrestricted diet, fast overnight, check glucose at baseline and 2 hours after glucose loading 2-hour blood glucose: ≥ 11.1 mmol/L = diabetes mellitus 7.8 to < 11.1 mmol/L = impaired glucose tolerance 255 Section 8. Miscellaneous Section 8: Miscellaneous 256 Section 8. Miscellaneous Chapter 89 – Management of eczema DK Ng - Avoid soaps, detergents, chemicals and abrasive clothing like woollen jumpers Aqueous cream or soft paraffin or emulsifying ointment as barrier cream to prevent loss of moisture, the main pathology of eczema skin. They can also be used as cleanser. Topical corticosteroid forms the main stay of treatment, cream for weepy lesion and ointment of dry lesions. For the face, only apply 1% hydrocortisone cream For the same concentration of medication, ointment is more potent than cream For weepy lesion, 1% acetic acid helps to dry up the skin For recalcitrant lesions, wet wrap with elomet cream diluted 10 times with aqueous cream may be applied at night with one layer of moist gauze overlaid with second layer of dry gauze to be washed off the next morning followed by emollient for a week. Potency of topical corticosteroid Preparation Potency 1% hydrocortisone acetate Mild Clobetasol butyrate (Eumovate) Moderate Fluocinolone acetonide (Synalar) 0.005% cream Moderate 0.0125% cream Moderate 0.025% cream Potent Mometasone furoate (Elomet) Potent Betamethasone valerate (Betnovate) Potent Clobetasol propionate (Dermovate) Very potent Topical immunosuppressant agents Tacrolimus (0.1%, 0.03% ointment) and pimecrolimus (1% cream) mainly for eyelids and periorbital skin. The FDA has recently issued a warning about these 2 drugs because of possible link of cancer with their use. Antibiotics Systemic antibiotics (flucloxacillin, or erythromycin in penicillin allergy) may be required in short courses during acute exacerbation If recurrent Staph aureus infection occurs, nasal and perineal swabs should be obtained from the patient and parents / carers. Carriers should be treated with topical mupirocin for about 10 days. Anti-histamines First generation of anti-histamines, e.g. piriton, atarax, are used for their sedative effect before bedtime 257 Section 8. Miscellaneous Chapter 90 – Infantile scabies KT Chan, F Poon,DK Ng Organism: Mite Sarcoptes scabiei var hominis – an obligate human parasite Presentation: - Generalized itch worse at night, especially over wrists, nipples, axilla folds and scrotum. - Pathognomonic burrows are rarely seen in infantile scabies - Nodules may be seen over scrotum - Erythematous papules, vesicles, pustules, bullae, and crusts can be present in all body areas including face Diagnosis: - Skin scrapings from the end of the burrow for microscopy to demonstrate mites, eggs or mite faeces (scybala) Management: Prophylactic treatment of all household contacts at the same time to prevent reinfection by those incuabing scabies (incubation period up to 2 months) Bed linen and clothings in skin contact during the 3 days before treatment must be washed with hot water and dried using a hot cycle (mite dies within 3 days without skin contact) Patient’s clothing, bed linen, pillow case should be washed separately from those of their family members in hot water (60oC or above) for not less than 10 minutes to kill the mites and their eggs. Place all non-washable personal items such as shoes, mattress in a plastic bag and seal them up for at least 14 days before they can be used as usual. Medications – must apply over the whole body, including head and face in infants and young children. For older children without face involvement, apply to whole body below the neck. Preferred treatment: 5% Permethrin cream for those older than 2 months: leave for 8-12 hours. Repeat application 1 week later 0.5% Malathion: leave for 24 hours. Repeat application 1 week later. However, neurotoxicity is a concern and it is not recommended in infants below 6 months of age 12.5% Benzyl benzoate: 3 applications in a 24-hour period. Apply the emulsion on the evening of Day 1. Allow to dry then apply a 2nd coat. Apply a 3rd coat on the following morning. Wash off on the evening of Day 2. However, it could lead to skin irritation. Dilution can reduce irritant effect but also reduce its efficacy. It is not recommended for infant or children Post-scabies treatment itchiness is very common and treated with antihistamines and/or topical corticosteroids, 10% Crotamiton cream 258 Section 8. Miscellaneous Chapter 91 - Fever of unknown origin DK Ng, C Tse Definition: 1) Documented fever for more than 7 days AND 2) Admitted for more than three days and assessed by second-round staff for at least 3 days AND 3) Absence of diagnostic features (clinical or otherwise) Causes: More than 95% of these cases in our experience were related to infection A few cases were related to autoimmune diseases 1 to 2 cases were related to drugs, hypothalamus control, haemophagocytosis, malignancy Review of symptoms and signs (from head to toes, from skin to viscera to sinuses) is VERY IMPORTANT as symptoms and signs are often present in retrospect. It is important to get the relevant signs and symptoms not in retrospect. Investigations: Infection: Viruses: Monospot, viral titres, dengue titre, NPA for respiratory viruses, HIV Small bacteria: cold agglutinin, mycoplasma titre, Weil-Felix, rickettsia Ab, B. burgdorferi Ab Bacteria: Mantoux test, Widal test, blood / stool / urine cultures, CXR Protozoa: fresh stool for amoeba, ultrasound of liver Parasites: blood smear for malaria, CPK, Brucella titre Fungi: blood culture Autoimmune: ANF, ANCA Malignancy: blood smear, urine for RBC, ultrasound of adrenal glands and kidneys Haemophagocytosis: bone marrow examination 259 Section 8. Miscellaneous Chapter 92 – Medical management of phimosis using topical corticosteroids MT Soo, DK Ng Phimosis is traditionally treated surgically but medical management may be offered if deemed appropriate by the attending clinician. Kikiros’ grading of phimosis (Kikiros, 1993): Retractability of foreskin: 0 – full retraction 1 – full retraction of foreskin and tight ring behind the glans 2 – partial exposure of glans 3 – partial retraction, meatus just visible 4 – slight retraction but distance between tip and glans (neither meatus nor glans could be exposed) 5 – absolutely no retraction (Indications for treatment: grade 3 to 5) Regime of topical corticosteroids (usually for Kikiros’ grade 5 phimosis): Betamethasone dipropionate: 0.05% cream BD for 1 month (Monsour, 1999) BD for 1-2 months (Wright, 1994)] Clobetasol propionate 0.05% (Dermovate) ointment daily for 1-2 months (Lindhagen, 1996) Betamethasone valerate 0.06% cream [BD for 2 weeks (Chu, 1999); BD for 4-8 weeks (Yang, 2005)], 0.05% ointment [BD to QID for 2-12 weeks (Kikiros, 1993)], 0.1% ointment [BD for 6 weeks (Ashfield, 2003)] Clobetasol butyrate 0.05% BD for 4-8 weeks (Yang, 2005) Triamcinolone: 0.02% [BD for 4-6 weeks (Ng, 2001)] Hydrocortisone: 1% and 2% [BD to QID for 2-12 weeks (Kikiros, 1993)] Treatment regime (Ku, 2007): Apply corticosteroid to the foreskin twice daily, after washing or bathing, for 4 weeks. After the foreskin becomes retractable, retract the foreskin gently without causing any pain, and wash the prepuce daily during bathing. Most papers advise to retract the foreskin as much as possible without causing pain or discomfort, and then apply a thin layer on the tightest part of the prepuce. Follow-up at 4 weeks: if phimosis does not resolve, give another 4-week course Maximum consecutive treatment period is limited to 8 weeks. Further treatment courses may be given if phimosis recurs. Topical steroid treatment should be combined with good hygiene practice of the foreskin with daily cleansing and retraction. It is worth noting that co-existing balanitis, history of urinary tract infection [Ashfield, 2003], age below 3 year [Elmore, 2002; Yang, 2005] are not contraindications for topical steroid treatment Contraindications: Buried penis (Chu, 1999) – poor response to treatment Balanitis xerotica obliterans (Monsour, 1999) – indication for circumcision 260 Section 8. Miscellaneous Mechanism: Make foreskin thinner, improve its elasticity and reduce any inflammatory component Allow the foreskin to be retracted and daily hygiene to be performed Cessation of steroid may lead to restitution of dermis and epidermis, known as rebound phenomenon Outcomes: Reported success rate: 67-100% Relapse rate: from 10-15% (Monsour, 1999) to 26.1% (Ku, 2007) Treatment with 0.05% betamethasone ointment for 4 weeks results in a success rate of 81.5% (defined as Kikiros’ grade 0 to 2). During follow-up, 60.2% of boys remained free from phimosis upon latest assessment. (Ku, 2007) 14.6% of the boys underwent circumcision because of failed treatment or recurrent phimosis. (Ku, 2007) No local or systemic side effects reported (except for a case of gynaecomastia after treatment with topical conjugated equine estrogen) (Yanagisawa, 2000) No significant change in early morning blood spot cortisol levels (Golubovic, 1996) Benefits: Avoid unnecessary circumcision and the risks of surgery and general anaesthesia Treatment cost: about 25% of circumcision (Van Howe, 1998) Allow urine surveillance in boys with history of urinary tract infection as proper exposure of meatus allows less contamination of urine with skin flora during voiding 261 Section 8. Miscellaneous Chapter 93 - Dental service for children S Cherk Dental service for children Normal Children Children with special needs School dental care service Designated dentists NGO dental clinic - primary school children - children on CSSA e.g. Yang Memorial Methodist Social Service - need subscription $20/year - list of dentists available from field unit of SWD 學童牙科保健 * ** * Government dental clinic 循道衛理 楊震社會服務處 ** HA dental clinics with provision for children with special needs - QEH - CMC - UCH - PMH Prince Philip Dental Hospital Government free extraction session for public: for pain relief and extraction only Need medical referral letter 262 Section 8. Miscellaneous Chapter 94 – Antibiogram C Tse Resistance of Common Bacterial Isolates in Paediatrics Department in Kwong Wah Hospital (2013) PICU NICU SCBU 38 0 0 0 0 10* 20 10 0 0 0 0 0 60 0 0 20 0 0 0 0 83 0 0 50 0 0 0 50 0 0 0 Nitrofurantoin 3 Meropenem 0 0 23 0 13 0 67 0 0 0 0 0 0 0 0 0 0 0 0 0 0 75 14 0 0 0 0 13 0 0 0 0 0 0 100 63 63 0 0 13 25 0 57 50 Cotrimoxazole Levofloxacin 20 0 0 100 Vancomycin Fusidic Acid Erythromycin 33 0 Cloxacillin 2 33 0 Amikacin 0 0 Gentamicin 1 0 Ceftazidime Cefotaxime 0 Cefuroxime (parenteral) 38 Sulperazon 4 0 Tazocin 83 100 Penicillin (parenteral) Escherichia coli (84)4 Klebsiella species (17)4 Staphylococcus aureus (10) Haemophilus influenzae (8) Pseudomonas aeruginosa (8) Enterococcus species (7) Streptococcus pneumoniae (7)5 Citrobacter species (5) Streptococcus agalactiae (group B) (4) Moraxella species (3) Escherichia coli (4)6 Staphylococcus aureus (3) Burkholderia cepacia (8) Staphylococcus, coagulase negative (8) Escherichia coli (7)6 Escherichia coli (10)6 Staphylococcus, coagulase negative (10) Penicillin PAD (exclude PICU, NICU, SCBU) Augmentin Organism (no. of isolates)1 Amoxycillin Unit Ampicillin % Resistance 0 0 0 0 14 30 29 30 * 1 strain from blood is borderline resistant to cloxacillin. 1 Organisms isolates from blood, urine and respiratory specimens. Interpreted according to CLSI. 2 Cloxacillin used to detect methicillin-resistant Staphylococci. 3 Urine isolates only. 4 Overall prevalence of extended-spectrum _-lactamases (ESBL) were 33% for E.coli, and 0% for Klebsiella species in PAD. ESBL-producing strains should be interpreted as resistant to all penicillins, cephalosporins and aztreonam. 5 In Streptococcus pneumoniae, resistance to azrithromycin & clarithromycin can be predicted by testing erythromycin (CLSI M100-S21). 6 Overall prevalence of extended-spectrum _-lactamases (ESBL) were 0% for E.coli in PICU, 14% for E.coli in NICU and 30% for E.coli in SCBU. ESBL-producing strains should be interpreted as resistant to all penicillins, cephalosporins and aztreonam. 30 30 14 30 0 80 50 20 0 0 0 0 22 ANTIBIOGRAM Prepared by Infection Control Team, Kwong Wah Hospital 263 0 0 0 0 Section 8. Miscellaneous Resistance of Common Bacterial Isolates in BLOOD in Paediatrics Department in KWH (2013) Cefotaxime Gentamicin Amikacin Cloxacillin 2 Erythromycin Fusidic Acid Vancomycin 0 0 17 33 83 0 67 0 0 0 33* 100 0 67 0 67 0 0 Meropenem Cefuroxime (parenteral) 17 Cotrimoxazole Sulperazon 100 Levofloxacin Tazocin Escherichia coli (6)7 Staphylococcus aureus (3) Staphylococcus, coagulase negative (3) Augmentin Organism (no. of isolates)1 Ampicillin % Resistance 50 0 0 0 * 1 strain is borderline resistant to cloxacillin. Top 3 Isolates from Paediatrics Department in KWH (2013) Unit PAD and PICU SCBU and NICU Organism Blood (n = 12) Staphylococcus aureus Salmonella species Staphylococcus, coagulase negative8 Blood (n = 17) Staphylococcus, coagulase negative8 Escherichia coli No. of isolates % of Total 3 2 25% 17% 2 17% 10 59% 6 35% 1 6% Bacillus species9 Organism Respiratory (n = 47) Staphylococcus aureus Haemophilus influenzae Pseudomonas aeruginosa (7) / Streptococcus pneumonia (7) Respiratory (n = 19) Burkholderia cepacia Staphylococcus, coagulase negative Acinetobacter species (2) / Escherichia coli (2) / Staphylococcus aureus (2) 7 Overall No. of isolates % of Total 9 8 19% 17% 14 30% No. of isolates % of Total Urine (n = 124) Escherichia coli Klebsiella species 87 13 70% 10% Enterococcus species 7 6% 9 36% 5 20% 9 36% Organism Urine (n = 25) 5 26% 3 16% 6 33% Escherichia coli Staphylococcus, coagulase negative Burkholderia cepacia (3) / Candida albicans (3) / Enterococcus species (3) prevalence of extended-spectrum _-lactamases (ESBL) were 17% for E.coli. ESBL-producing strains should be interpreted as resistant to all penicillins, cephalosporins and aztreonam. were skin contaminant in PAD + PICU and 70% were skin contaminant in SCBU + NICU from blood. 9 Common skin contaminant from blood. 8 100% 264 Section 8. Miscellaneous Chapter 95 - Megavitamin Cocktail Regimen Freddie Poon Megavitamin Cocktail Regimen Daily dose Route Availability Examples of related conditions Thiamine 50mg IV/PO Formulary drug mitochondrial disorders, MSUD, PDH deficiency, complex I deficiency Riboflavin 100mg - 300mg PO Formulary drug glutaric aciduria type I/II, mild variants of ETF, ETF-DH, complex I deficiency (congenital lactic acidosis) Biotin 10mg PO Non-formulary drug Pyridoxine 100mg IV Formulary drug pyridoxine dependency with seizures, homocystinuria, primary hyperoxaluria type I Vitamin B12 1mg IM/SC/PO Formulary drug methylmalonic academia, homocystinuria Ascorbic acid 100mg/kg PO Formulary drug tyrosinaemia III, transient tyrosinaemia of the newborn, glutathione synthase deficiency, abetalipoproteinaemia Carnitine 25mg/kg Q6H PO Formulary drug organic acidaemia, carnitine deficiency Co-enzyme Q10 5mg/kg PO Formulary drug respiratory chain defects Pyridoxal phosphate 20mg/kg PO Non-formulary drug PNPO deficiency: pyridoxal phosphate responsive seizures Folinic acid 20mg PO Non-formulary drug hereditary orotic aciduria, methionine synthase deficiency, cerebral folate transporter deficiency, hereditary folate malabsorption, Kearns-Sayre syndrome multiple carboxylase deficiency (biotinidase, holocarboxylase synthetase) updated on Oct 2013 Indication:Megavitamin cocktail therapy should be considered in those patients who present with an acute severe illness of unknown aetiology in which inborn error of metabolism is highly suspected. This may be in the form of emergencies such as encephalopathy, seizures, liver failure, metabolic acidosis, shock or others. Therapy should commence as soon as possible, and should be directed to reduce the formation or enhance the secretion of toxic metabolites, provide adequate calories and prevent catabolism, and to provide co-factors empirically if a specific diagnosis is not established. Appropriate immediate treatment not only improves survival but also reduces the chances of neurodevelopmental sequelae. 265 Section 8. Miscellaneous Chapter 96 - Immune Thrombocytopenia (ITP) KL Kwok, TH Fung, MT Soo, E Chan Definition and Terms (ASH 2011): Primary ITP as a platelet count < 100 x 10^9/L in the absence of other causes or disorders. - Newly diagnosed (diagnosis to 3 months) - Persistent (3 to 12 months from diagnosis) - Chronic (lasting for more than 12 months) Secondary causes of immune thrombocytopenia: - Anti-phospholipid syndrome - Autoimmune thrombocytopenia (e.g. Evans syndrome) - Common variable immune deficiency - Drug administration side effect - Infections: CMV, Helicobacter pylori, hepatitis C, HIV, varicella zoster - Lymphoproliferative disorders - Bone marrow transplantation side effect - Vaccination side effect - Systemic lupus erythematosus Diagnosis of primary ITP: Careful history-taking + physical exam + review of CBP and peripheral blood smear History: Isolated bleeding without constitutional symptoms P/E: No hepatosplenomegaly, lymphadenopathy or skeletal abnormalities CBP: Isolated low platelet < 100 × 10^9/L; anaemia only if due to significant bleeding, otherwise normal red cell indices, white cell count and differentials Peripheral blood smear: normal or large platelets; normal red cell and white cell morphology Any atypical features should prompt more investigations accordingly. Bone marrow examination in children and adolescents with typical features of ITP is unnecessary; it is also unnecessary for those who fail IVIG therapy. Some suggested it is also unnecessary before initiation of steroid and before splenectomy. Management: - No intramuscular injection, arterial puncture or deep vein puncture - Avoid contact sports - Avoid drugs that increase bleeding: e.g. NSAIDs and aspirin 266 Section 8. Miscellaneous Drug treatment: - Aim for haemostasis, not “normal” platelet count Children with typical features of ITP No bleeding, or only mild bruising / petechiae on skin No mucosal bleeding Mucosal bleeding or significant bleeding Conservative management regardless of platelet count* (need discussion with family) # i) IVIG (faster rise in platelet) ii) or short course of steroid iii) or anti-D (less effective) *For practical purposes, consider treatment if (i) platelet count < 10 x 10^9/L, or (ii) platelet count 10-30 x 10^9/L and clinical bleeding including mucosal bleeding. Platelet count of >30 x 10^9/L is considered safe, but aim for >= 50 x 10^9/L for minor procedures. Consider lower threshold for treatment if there is a higher risk of bleeding due to patient’s activity level, or if follow-up cannot be ascertained. # i) IVIG (preferred): 0.8-1 gram/kg over 4 hours (slower initial infusion) - initial response 1-3 days, peak 2-7 days ii) Steroid: no evidence to support any one dose or dosing regimen over others - Oral prednisolone 2 mg/kg/d for 2 weeks then taper over 1 week (preferred) - Oral prednisolone 4 mg/kg/d for 7 days then taper - initial response 2-14 days, peak 4-28 days iii) anti-D: 50-75µg/kg IV over 10 min for Rh-positive, non-splenectomized children - not for those with decreased Hb or evidence of autoimmune hemolysis - initial response 1-3 days, peak 3-7 days 2nd line treatment (rarely needed): - high dose steroid, rituximab, azathioprine, cyclosporin, MMF, other immunosuppressants; splenectomy Splenectomy: - Chronic symptomatic thrombocytopenia lasting for > 12 months (> 12-24 months in the British guideline) and a platelet count < 10 x 10^9/L being unresponsive to standard treatment and presenting with no surgical contraindications - Rarely recommended in paediatric ITP cases Monitoring: - Check platelet count initially 1-2x/week and post drug treatment; when a trend is observed, gradually space out till platelet count normal for few months - Recurrence of acute ITP is rare 267 Section 8. Miscellaneous Prognosis: - 75-80% should be expected to go into remission by 6 months - Chronic disease (platelet < 150 × 10^9/L in study by Kuhne) is more common in older children. > 3 months to < 12 months: 23.1% > 12 months to < 10 years: 28.1% > 10 years: 47.3% Persistent / chronic ITP: - Recommend re-evaluation if no improvement after 3-6 months: bone marrow (if ITP persists or no prior response to treatment) - Evaluate for infection (HIV/HCV/H pylori) if clinical suspicion or high local incidence - ANA, anti-phospholipid Ab; immunoglobulins - Review medications - Periodically reconsider (every 6-12 months) other diagnoses Management of persistent / chronic ITP: - Drug treatment does not alter the chance of recovery - Management of children with persistent/chronic ITP is essentially the same as those with newly diagnosed ITP i.e. to maintain a haemostatic platelet count with first-line therapies (e.g. IVIG, anti-D, short course of steroid) and to minimize the use of prolonged steroid therapy - Many children stabilize with an adequate platelet count (> 20-30 x 10^9/L) and are asymptomatic - Majority of chronic ITP children do not require treatment - Some children with ITP and platelet counts of 10-30 x 10^9/L may be troubled by purpura although no significant bleeding; treatment may be beneficial in these cases Prognosis of chronic ITP: - ~66% spontaneous remission within 5 years; 10-15% of patients per year achieve normalization of platelet count during this time period ITP and emergency treatment: - Severe or life threatening bleeding - IVIG + high dose steroid (e.g. 30 mg/kg methylprednisolone daily for 3 days, ASH guideline 1996) - Platelet transfusion (larger-than-usual dose, 2- to 3-fold usual dose) ITP and surgery: - A platelet count of > 50 x 10^9/L is considered sufficient in chronic ITP for a normal surgical intervention, with the exception of neurosurgery and high-risk surgery (AIEOP Consensus Guidelines 2010) 268 Section 8. Miscellaneous Chapter 97 - Haemophilia TH Fung, MT Soo, E Chan I. Introduction - Haemophilia A (85% of cases ) and B (15% ) - X-linked recessive, rarely affect female (extreme lyonization) - Incidence - haemophilia A: 1 in 5,000-10,000; haemophilia B: 1 in 30,000-50,000 II. Diagnosis - Family history: affected male; up to ~1/3 de novo mutation - Prolonged APTT in moderate to severe cases (may be normal in mild cases) - Factor assay < 40% Clinical classification of patients with either haemophilia A or haemophilia B Severe haemophilia Moderate haemophilia Mild haemophilia Factor level < 1% Factor level 1-5% Factor level 6-40% Spontaneous bleeding Characteristic Can bleed with slight injury May bleed 1-2 times per week May bleed once per month Bleeding typically only with severe injury, surgery, invasive procedures May never have a bleeding problem Characterized by joint May have joint bleeding Rarely has joint bleeding bleeding (haemarthrosis) - severe haemophilia account for 70% of cases - refer patient’s immediate female relatives to check for factor level (carriers may have abnormal factor level and caution needed before surgery) III. Incidence of different sites of bleeding - Haemarthrosis: 70-80%, muscle/soft tissue: 10-20%, central nervous system (CNS) bleeding <5%, other major bleeds: 5-10% Incidence of bleeding into different joints - Knee: 45%; elbow: 30%; ankle: 15%; shoulder: 3%; wrist: 3%; hip: 2%; others: 2% IV. Principles of management - goal -prevention of bleeding - Treat bleeding early: < 2 hours of onset of symptoms - During bleeding: R (rest) I (ice) C (compression) E (elevation) - Treat veins with care - Avoid drugs that cause platelet dysfunction e.g. NSAIDs, aspirin - Clotting factor concentrate replacement or DDAVP prior to invasive procedures - Multidisciplinary approach Alert card/letter to patients (available in department web) 269 Section 8. Miscellaneous V. Management of bleeding episodes i) Haemophilia A: Factor VIII concentrate (FVIII) - Each FVIII unit/kg raises plasma FVIII level by 2% - Dose (unit) = BW (kg) x desired % level rise x 0.5 - 1/2 life = 8-12 hours, with individual patient response - slow iv; not > 100 units/min in children (not > 3 ml/min in adults) - Give the entire vial of FVIII even it exceeds the calculated dosage (in moderate and severe haemophilia) - Continuous infusion by experienced haematologist: 50 U/kg bolus followed by 4-5 U/kg/hr provides ~100% FVIII level in severe haemophilia - Monitor factor level daily DDAVP - In mild haemophilia (or moderate), can raise level to 2-8x baseline - Need pre-testing of response (Challenge test: 0.3 mcg/kg in 30-50 ml NS over 15-30 minutes. Check factor level at 1 hour: +ve response = FVIII ≥2x baseline and >30%) - Given as daily dose - Tachyphylaxis: decreased response after 1-2 days - Avoid using in children < 2 years old - Fluid restriction to 3/4 of maintenance Anti-fibrinolytic agents - As treatment for minor mucosal bleeding or as adjuncts in more severe mucosal bleeding, e.g. Tranexamic acid (25 mg/kg po or 10-15 mg/kg iv q8h for 5-10 days) - should not be given concurrently (wait for 4-6hrs) with non-activated or activated prothrombin complex concentrate (PCC) as potential thrombotic complications - Not to be used in urinary tract bleeding or thoracic surgery Recombinant activated factor VIIa (Novoseven): - Used in those with inhibitors; dosage: 90 mcg/kg q2-3h until haemostasis (adjust to nearest vial, dosage from 35mcg to 120mcg/kg has been used with success); for severe bleed that requires longer duration of treatment to maintain post haemostatic plug, dosage adjusted to q3-6h in the post haemostatic stage 270 Section 8. Miscellaneous ii) Haemophilia B: Factor IX concentrate (FIX) (currently pure factor IX) - Each FIX unit/kg raises the plasma FIX level by 1% - Dose (unit) = BW (kg) x desired % level rise (lower bioavailability for recombinant FIX : thus a multiplication factor of 1.2 for adult, 1.5 for children) - Half-life = 18-24 hours, subject to individual patient response - Slow iv, no more than 100 unit/min in children or 3 ml/min in adults - Continuous infusion by experienced haematologist - monitor level Anti-fibrinolytic agents or Recombinant activated factor VIIa-as in haemophilia A - (Note: Cryoprecipitate does not contain FIX; FFP is also not recommended; DDAVP has no value in haemophilia B) Desired plasma factor level and dosage for bolus infusions Type of haemorrhage Joint (children) - initial (1st dose; if target joint- first day) - subsequent CNS/head* - initial ( 1st dose) - maintenance (long term prophylaxis) Throat and neck* - initial (1st dose) - maintenance GI - initial ( 1st dose) - maintenance Ophthalmic - initial (1st dose) - maintenance Surgery - initial (1st dose) - maintenance Iliopsoas muscle - initial (1st dose) - maintenance Muscle (except iliopsoas) Haemophilia A dose (units/kg) Haemophilia B dose (units/kg) X 1.5 times for recombinant IX 80-100% (subsequent 40-50%) 40-50 Then 20-25 (q12h) 80-100 Then 40-50 (q24h) 80-100% >50% 40-50 25 (q12h) 80-100 50 (q24h) At least 7-10 days; usually 2-3 weeks until haemorrhage improved on imaging 80-100% >50% 40-50 25 (q12h) 80-100 50 (q24h) Until bleed resolves; at least 12weeks 80-100% 50% 40-50 25 (q12h) 80-100 50 (q24h) 7-14 days until origin of bleeding identified and treated 80-100% >50% 40-50 25 ( q12h) 80-100 50 ( q24h) 80-100% 50% 40-50 25 (q12h) 80-100 50 (q24h) 5-14 days, depending on type of surgery 80-100% >50% 40-50 25 (q12h) 80-100 50 (q24h) 2-4 days; may be longer as dictated by symptoms 50% 25 50 50-100% 25-50 50-100 5-7 days 50% 25 50 3-5 days Desired level Duration 1-3 doses till pain largely subsided; longer if response inadequate Until healing 2-3 days; longer if inadequate response Deep laceration Renal *medical emergency 271 Section 8. Miscellaneous Oral bleeding - anti-fibrinolytic alone, or with factor (aim level 30-40%) if bleeding is prolonged, significant or difficult to control - Mouthwash with anti-fibrinolytic (eg tranexamic acid 250mg in 10-20ml water) - Topical thrombin/fibrin glue, ice popsicle/custom-fit mouth piece; soft cold diet Epistaxis - Factor is usually not needed - Head forward, firm pressure to the fleshy part of the nose for at least 10-20 min - Anti-fibrinolytic, intranasal NaCl gel and nose clips - ENT consultation if significant/ difficult control of bleeding VI. Prophylaxis - Primary prophylaxis (the ideal treatment): start at < 2 years old, before or after the first haemarthrosis - Secondary prophylaxis: after the second episode of haemarthrosis - Primary/secondary prophylaxis should be offered to all severe haemophilia patients - Regimen: - High dose: 25-40 units/kg 3x/week for haemophilia A; 30-50 units/kg 2x/week for haemophilia B; aim trough > 1% - In some, low dose: 20 units/kg 1-2x/week for haemophilia A; 30-40 units/kg 1-2x/week for haemophilia B; titrate clinically - Dose escalation protocol: 1st step : 50 units/kg once/ week -> 2nd step: 30 units/kg 2 times/week -> 3rd step: 25 units/kg QOD (3 times/week) Step up when 3+ bleeds into any one joint over 3 months OR 4+ bleeds into any soft tissue/ joint over 3 months OR 5+ bleeds into one joint - WHO and WHF recommend indefinite primary prophylaxis but many discontinue as adults - patient with target joints but refuse long term prophylaxis, short-term secondary prophylaxis for 4-8 weeks (+ physiotherapy or synoviorthesis) VII. Surgery - Best in Haematology centre - Document individual response to replacement therapy prior to surgery; ensure adequate factor concentrates availability - Immediately prior to surgery: aim level 80-100%, then maintain at least 50% - Monitor factor levels serially during surgery and then at least daily - Continuous infusion may be preferable if data of stability for continuous infusion of factor concentrates available - Maintenance: 5-7 days for minor surgery; 10-14 days for major surgery - Prophylaxis 3-4x/week for 6 weeks for orthopaedic procedures during rehabilitation 272 Section 8. Miscellaneous VIII. Special procedures - Factor coverage for LP, ABG, bronchoscopy, liver bx, endoscopy with brushings/bx IX. Dental care - Ensure good dental and oral hygiene - Oral infections should be treated with antibiotics before any dental procedures - No factor concentrates needed for routine dental examination and cleaning - Factor concentrates (and anti-fibrinolytics or DDAVP for mild haemophilia) for deep cleaning, scaling, or removal of heavy plaque or calculus - Always factor concentrates if needs local anaesthesia block, aim level > 50% - Raise level to 50-100% if dental extraction, by factor concentrates and anti-fibrinolytics (anti-fibrinolytic x 10 days until sutures removed and wound healed) - Bleeding associated with 1’ teeth exfoliation managed as in oral bleeding; those with hx of prolonged bleeding on tooth exfoliation, consider tooth extraction under factor concentrate cover - Hospitalize for extensive procedures - In teenage patients, evaluate for wisdom teeth and consider early extraction X. Other precautions - Sports: i)Encourage low impact activities to strengthen muscle e.g. swimming, golf ii)Use protective gears iii) High impact sports not advisable e.g. football - Immunizations: - Follow the routine vaccination schedule but no imi; administer subcutaneously instead and apply pressure at injection site for 5 minutes XI. Complications Factor inhibitor formation: - Suspect when no response to usual dose of factor concentrates - screen for inhibitors Q 3-12 months or Q10-20 exposure days (whichever occurs first); for adults, screen as clinically indicated - screen for inhibitors if patients switch to a new factor concentrate - Low-responding inhibitor - specific factor replacement at a much higher dose (2-3x); patients with hx of high responding inhibitor but with low titres may be treated similarly in an emergency, until an anamnestic response occurs, usually in 3-5 days - At a high inhibitor titre (≥ 5 BU), specific factor replacement unlikely effective without high dose continuous infusion therapy; use bypassing agents in such cases e.g. recombinant factor VIIa and PCC, including the activated ones such as FEIBA® /Autoplex® Other complications: - Chronic synovitis, chronic haemophilic arthropathy, fracture, infection, pseudotumour, allergic reaction 273 Section 8. Miscellaneous Chapter 98 - Management of Haemangioma with Propranolol KT Chan, Dr L Leung Course of infantile haemangioma (IH) - Most start proliferating noticeably between 2-4 weeks of age. - Most rapid proliferation phase – first 6-8 weeks of age; 80% of maximum size reached by 3 months; 80% have completed growth by 5 months. Max size 9-12 months for almost all. - Segmental & deep IH may longer growth phase. - Regression – 50% max involution by 5 years, 70% by 7 years, 90% by 9 years. - Up to 70% leave residua in studies (telangiectasia, fibrofatty plaques, atrophic scar, loose skin) NB. associated complications of haemangiomas: - Lumbosacral: high resolution US spine in ≤ 3 months; MRI in ≥ 6 months - LUMBAR association, segmental genital and lower extremity haemangioma: US abdomen, pelvis for genitourinary and anorectal anomalies, - Segmental facial haemangiomas: MRI & MRA for head and neck, echocardiogram for brain/ vascular anomalies/ coarctation & eye consultation for PHACES. - Multifocal (≥5 skin lesions: may visceral involvement like liver/ GI involvement) Possible mechanisms of action of propranolol - Vasoconstriction, inhibition of angiogenesis, and induction of apoptosis Consult skin clinic doctor for cases considering treatment (at 1-2 mths old). Treat BEFORE or EARLY in rapid growth phase. Decision to treat: based on IH location, size, slope, depth, age of patient, extent of growth and likelihood of future growth, presence and risk of complications. Discuss with parent. Examples are: - - Lesions that are likely to involve airway (mandibular, “beard distribution” including parotid or neck area) or obscure vision (peri-orbital area) or cause obstruction/ necrosis (nasal, ear or pinna) Lesions that are at high risk of ulceration/ bleeding (perioral location, perineal area, buttock, axilla, sites which are likely to rub against clothes). Central facial lesions that may cause more residue and potential disfigurement Segmental lesions (occupy subunit of a body part- 11x risk of complications) Lesions that are likely to grow longer and leave residua (deep haemangiomas, nasal tip, lip, parotid, head & neck) Multifocal/ diffuse hepatic haemangiomas: cardiac overload, consumptive hypothyroidism. IMPORTANT: For lesions likely fall into above categories: follow-up every 2-4 weeks in first 2-5 months of life: Aim to treat BEFORE active proliferative phase, but may still be useful in children up to 15 months old. Small superficial haemangiomas: topical timolol 0.5% (eyedrop formulation) 3-4x per day for 4-6 weeks may be effective if given early. Follow closely, consider systemic β-blocker if not responding. Contraindications to propranolol - Sinus bradycardia, hypotension, greater than first-degree heart block, heart failure, asthma, hypersensitivity to propranolol, cardiogenic shock - Special precaution – PHACE syndrome (Discuss with senior if facial haemangioma > 5cm) 274 Section 8. Miscellaneous Baseline investigations - CBC, RFT, LFT, Glucose (preferably before feed), TFT - ECG (advised when the HR is below normal, arrhythmia detected on cardiac exam, or there is a family history of arrhythmias or maternal history of connective tissue disease) Propranolol regimen (inpatient) - First day – 1mg/kg/day po ÷ BD or TID - Second and subsequent days – 2 mg/kg/day po ÷ BD or TID - Feeding should be given shortly after propranolol (For high risk patients: ≤1 month old, premature or hx of hypoglycemia: First day - start 0.5mg/kg/day po ÷TID, subsequent increase as above) Sites that are less responsive (e.g. parotid area) may need doses up to 3mg/kg/day Monitoring - Baseline and Hourly AR / BP at first 2 hours after each dose of propranolol (peak effect on HR and BP is 1 to 3 hours, especially after first dose and significant dose increase of >0.5mg/kg/day) - Inform if AR / BP less than age-specific range. - Dextrostix before feed - Inform if sweating, jitteriness, irritable, lethargy, poor feeding – may be subtle symptoms of hypoglycaemia - Discharge D3 if tolerated. Side effects - More common: changes in sleep (fatigue, insomnia, nightmares, night restlessness, sleep disturbance) and acrocyanosis - Less common but serious: Hypotension, hypoglycaemia, bradycardia - Others: respiratory symptoms (infections, wheeze), GI symptoms (GOR, diarrhoea), irritability or agitation, profuse sweating, rash and temporary hypotonia, hyperkalaemia Advice to parents - Propranolol should be withheld during intercurrent illness (risk of hypoglycaemia) - Child who need to fast during procedures / investigations should have glucose-containing fluids (as ORS or IV fluid) Duration of treatment - Minimum for 11 months; usually keep till 15 to 18 months (rebound is more frequently seen if propranolol is stopped before 1 year old) - Nodular haemangioma on sites that involute slowly may need treatment for 2-3 years Tapering of treatment - Propranolol should be tapered over 1-3 months to avoid rebound tachycardia, stepwise by 0.5mg/kg/day. Other treatment options for systemic β-blockers: nadolol or atenolol. 275
