1. Pediatric ED Case Conference Date: 2006/04/25 Presented by R1 劉政忠 Instructor: MA 張玉吉吉 醫師 MA 吳孟書 醫師

2. General data  Name: 張 X 浩  Chart number: 20947975  Age: 3 week 2 day-old  Gender: Male  Body weight : 3kg

3. Vital sign  2006-3-29 12:43 (0hr0min)  T:36, P:165, R: 65  E4V5M6, SpO 2 :93%  檢傷分類 : 3 級  病患主訴因食慾差  Chief complaints: SOB for 2 days

4. Present illness  Vomiting for 2 days  No cough  Poor appetite(+)  看起來很乾 ?

5. Past history  Nil

6. PAT  Appearance: ?  Breathing: tachypnea  Circulation: ?

7. Physical examination  General appearance: poor activity  HEENT: lip cyanosis, dry lip  Chest: bil coarse BS, wheezing(+), rales(+), retraction(+)  Heart: RHB  Abdomen:?  Extremity:?  Skin:?

8. ED initial impression  r/o GER  r/o aspiration pneumonia

9. Further history taking  Dyspnea? Cough? Foreign body? Cyanosis?  Vomiting? Content? Projectile? Feeding? Diarrhea? Urine amount? Body weight change?  Fever?  Activity? Appetite?  Drug hx?  Birth hx: BBW? IUGR? Preterm baby?CHD?  Maternal hx: GDM? PROM?

10. Further PE  Appearance: TICLS  HEENT: frontanelle, tears, dry mouth or mucosa, throat, nasal flaring, accessory muscle use  Chest: retraction, breathing sound  Heart: murmur  Abdomen: soft or distension, tenderness, bowel sound, umbilicus, mass  Skin: rash, turgor, pallor, cyanosis, CRT

11. Detail Hx from admission note(1)  Birth hx: G1P1 GA:39+weeks, NSD, APGAR score? Born in LMD, BBW: 2850g, BH: 50cm, NB screen:?  Drug hx: 八寶粉 topical use?  Vaccine: HBV on 95-3-10  Maternal hx: 20y/o,G1P1, No maternal fever, no PROM, no chorioamnionitis, no maternal GDM, no PIH, no eclampsia, and no use of drug during pregnancy

12. Detail Hx from admission note(2)  3 days ago….  Vomiting  decreased appetite (80~100cc to 20~30 per meal)  progressive tachypnea, cyanosis when feeding  BW: 2850 to 2880g (<3rd percentile)

13. Detail PE from admission note(1)  General appearance : ill looking, poor activity and irritable  HEENT : grossly normal, no facial dysmorphism, no anterior or posterior frontanel bulging, no icteric sclera, no neck mass, no periorbital edema  Heart : regular heart beat, no murmur  Chest : coarse breath sound, no wheeze, no rales, tachypnea and obvious subcostal or supraclavicular retraction, mild nasal flaring

14. Detail PE from admission note(2)  Abdomen : soft, flat, no distension, normoactive bowel sound, no abnormal palpable mass, no pus discharge from umbilical area, no hepatosplenomegaly, no perianal redness  Genital organ : grossly normal  Extremity :no edema, distal four limb : warm and pink, no limb cyanosis, peripheral pulse palpable, capillary refill time < 2 sec  Skin: no rash  Neurologic examination : muscle power : +5/+5, no hypotonia

15. How about this baby?  Respiratory distress + dehydration + poor activity => ? Infection: pneumonia, UTI, viral infection… Endocrine and metabolism: electrolyte imbalance, Inborn errors of metabolism, Hypoglycemia… GI: pyloric stenosis, AGE, T-E fistula, obstruction…

16. Initial order 3/29 13:18 (0hr35min)  CXR  CBC/DC, CRP, AST, ALT, BUN, Cr, Na, K, Cl, Ca, sugar, CRP, B/C*1  IVF: D5S1/4 run 15cc/hr  O2 hood  A+B inhalation st  NPO

18. Lab—hemogram  WBC 21400  Hemoglobin 15.5  Hematocrit 43.9  Platelets 60000  Segment 48.0 %  Band 1.0 %  Lymphocyte 41.0 %  Monocyte 5.0 %  Eosinophil 5.0 %

19. Lab--biochemistry  Sugar 615 !!  BUN (B) 17  Creatinine(B) 0.5  AST (GOT) 23  ALT/GPT 22  Calcium 10.4  Na 125  K 5.7  Cl 96  CRP 0.83

20. 3/29 14:45(2hr02min)  Admission to NICU

21. 3/29 15:10(2hr27min)  IVF 改 half saline run 15cc/hr  補 ketone body(B) => 3+

22. Admission impression  Vomiting and severe dehydration  Severe metabolic acidosis  Respiratory distress and cyanosis episode, r/o sepsis  Leukocytosis and thrombocytopenia

23. Admission order 3/29 16:06(day1)  IVF: D2.5S1/2 IV+ PO 140cc/q8h (150cc/kg/day)  NPO  Check F/S stat and q8h  On OG tube  U/C, U/A, urine GBS Ag  Sugar, NA, K, Ca, Cl, ABG  Ampicillin 70mg q6h iv + GM 7mg q8h ivf

24. U/A  Color Yellow  Turbidity Clear  SP.Gravity 1.025  pH 5.0  Leukocyte Negative  Nitrite Negative  Protein Negative  Glucose 1.000  Ketone 2+  Urobilinogen 0.1  Bilirubin Negative  Blood 2+  RBC 6  WBC 0  Epith-Cell 0

25. ABG and biochemistry  TEMP 37°C  PH 7.148  PCO2 7.0  PO2 130.5  HCO3 2.4  SBE -26.5  SAT 97.9%  Sugar 715  Calcium 10.3  Na 128  K 4.8  Cl 96  AG: 29.6  Osmo(C): 301.7

26. Hospital course 3/29 (day 1)  16:20 on nasal CPAP  16:45 NS challenge 40cc, jusomine 8mL ivf  21:00 F/S:524 N/S challenge 30cc IVF 改 HS run 40cc/hr RI 10U in N/S 500 rum 3mL/hr  21:25 on endo

27. Hospital course 3/30 (day 2)  01:00 F/S:266, RI line 改 run 2mL/hr  07:00 jusomin 8mL ivf IVF 改 D0.225 + 5mL KCl run 140/q8h consult endocrine check Osmo(B): 301 => OG: normal  23:00 F/S:216 RI line 改 run 0.5mL/hr

28. Hospital course  3/31(day 3): extubation DC RI line 改 NPH 0.5U SC q8h  4/1(day 4): try feeding  4/4(day 7): DC anti  4/6(day 9): NPH 1U SC q8h  4/12(day 15): 轉 5L  4/17(day 20): 轉 7L, NPH1.25U SC q8h  4/18(day 21): MBD and OPD F/U

29. Other study during hospitalization  Abdominal echo=> negative findings  Serum amylase and lipase=> normal  C peptite=> 0.34(low 0.47~3.15)  Insulin antibody=> P11.0(>10)  HbA1C=> 9.6.%  Urine GBS Ag, U/C and B/C=> negative

30. Final diagnosis 1. Neonatal DM (type 1 DM) under NPH control, complicated with DKA and severe dehydration 2. Thrombocytopenia post blood transfusion 3. Respiratroy distress due to severe metabolic acidosis with respiratory compensation

31. Discussion DDx of hyperglycemia in infant DKA in childhood Management of DKA Neonatal DM

32. The ill-appearing infant:DDx(1)  Infectious: Bacterial sepsis, Meningitis, Urinary tract infection, Viral infections…  Cardiac: CHD, SVT, MI, Pericarditis, Myocarditis, Kawasaki disease  Endocrine: CAH  Metabolic: Hyponatremia, hypernatremia, Cystic fibrosis, Inborn errors of metabolism, hypoglycemia Textbook of Pediatric Emergency Medicine, 5th edition

33. The ill-appearing infant:DDx(2)  Drugs/toxins—aspirin, carbon monoxide  Hematologic: Severe anemia, Methemoglobinemia  Gastrointestinal: Gastroenteritis with dehydration, Pyloric stenosis, Intussusception, Necrotizing enterocolitis, Appendicitis, Volvulus  Neurologic: Infant botulism, Child abuse=> ICH Textbook of Pediatric Emergency Medicine, 5th edition

34. Hyperglycemia in infant: DDx More often in premature infant  Excess glucose administration IVF, feeding  Inability to metabolize glucose Premature, sepsis, stress  Neonatal DM Rare, 2 days ~ 6 weeks, C-peptide may be normal or transiently low  Medications Caffine, theophylline, steroid, phenytoin  Type 1 DM Vary rare, low to absent C-peptide level LANGE clinical manual, Neonatology: management, principle, on-call problems, disease and drugs. 5 th edition(2004)

35. DKA in childhood  Type 1 diabetes: the most common pediatric endocrine disorder  Prevalence: 1/400  Islet-cell autoantibody, insulin antibody, glutamic acid decarboxylase antibody  27 ~ 40% of new-onset diabetics present in DKA  The leading cause of mortality in diabetics < 24 y/o  cerebral edema: the leading cause of mortality

36. Definition  metabolic acidosis (pH <7.25 to 7.30 or serum bicarbonate <15 mEq/L)  hyperglycemia (serum glucose >300 mg/dL)  ketonemia

37. Clinical feature  Polyuria, polydipsia, dehydration, ketotic breath, hyperpnea, nausea, vomiting, abdominal pain, general malaise, coma  The most common cause: poor compliance  Viral illness and focal infections such as urinary tract infection or gastroenteritis

38. Life-threatening complications  Cerebral edema  Cardiovascular collapse  Profound metabolic acidosis  Hyperkalemia  Hypokalemia  Hypophosphatemia

39. Risk Factors for Cerebral Edema in DKA  Elevated BUN  Low PCO2  Treatment with bicarbonate  Failure of measured serum [Na] to rise steadily with correction of hyperglycemia  Age <3 y  New-onset diabetes

40. Initial lab evaluation  CBC  Glucose  Electrolyte (Na, K, Ca, P, Cl)  blood gas  Serum osmolality  ketones  Urinary ketones  Lactate

41. Management(1)  10–20 mL/kg NS bolus until hemodynamically stable  Then begin 0.45% NS(or 0.9%NS) at 1.5 times maintainance  K (if patient is urinating ) add 30 mEq/L. 2.5–3.5 mEq/L=> add 40 mEq/L consider adding more

42. Management(2)  RI at 0.1 units/kg/hr after intravenous fluid bolus. Adjust dose to maintain glucose decline at 50–100 mg/dL/hr.  Add dextrose to intravenous fluids when BS is <200–250 mg/dL.

43. Management(3)  Avoid bicarbonate therapy in DKA. Only consider arterial pH<6.9 impaired cardiac contractility and vascular tone life-threatening hyperkalemia.  Follow serum electrolytes q2h.  Follow serum glucose every hour

44. Neonatal DM, NDM(1)  Hyperglycemia that occurs during the first one month of life  Require insulin tx and last more than 2 weeks  A rare dx with incidence:1/500000 neonates  IUGR, SGA, hyperglycemia, dehydration, glucosuria, acidosis with or without ketouria Permanent neonatal diabetes mellitus manifesting as diabetic ketoacidosis. Journal of the Formosan Medical Association. 102(12):883-6, 2003 Dec.

45. NDM(2)  Transient NDM Insulin can be discontinued after several weeks or months Maturational delay of the adenyl cyclase-cAMP system of islet cells  Permanent NDM pancreatic agenesis or hypoplasia or absent beta cells Gene mutations: ATP-sensitive potassium channel subunit Kir6.2  Type 1 DM Autoimmune dx Manifests later in life Permanent neonatal diabetes mellitus manifesting as diabetic ketoacidosis. Journal of the Formosan Medical Association. 102(12):883-6, 2003 Dec.

46. NDM(3)  In a series of 57 infants with NDM  18=> Transient  13=> Transient with recurrence between 7~20 y/o  26=> Permanent Long-term course of neonatal diabetes. N Engl J Med 1995; 333:704.

47. Case report of TNDM Age of onsetBBW(gw)Duration of Insulin tx Case 133 days32005 months Case 249 days34004.9 months Case 349 days240010 months Case 460 days13002 weeks Different faces of non-autoimmune diabetes of infancy. Acta Paediatrica. 87(1):95-7, 1998 Jan

48. Case report of PNDM  A case of PNDM in a 3-day-old female infant.  This full-term neonate was born small for gestational age.  Respiratory distress, poor activity, hypothermia, poor feeding, dehydration, and ketoacidosis.  After insulin therapy and fluid replacement, her condition became stable.  Serum C-peptide level to be low for her age.  During the first year of life she had catch-up growth, but insulin therapy was still required. Permanent neonatal diabetes mellitus manifesting as diabetic ketoacidosis. Journal of the Formosan Medical Association. 102(12):883-6, 2003 Dec.

49. PNDM in Oman(1)  All children(5) diagnosed as having PNDM between 1991 and 1995 in Oman were included in the study  The mean incidence: 2.2 per 100 000 live births/year  IUGR was noted in all (mean BBW 1.86 kg)  DKA in 80%  Circulating islet cell antibody: (-) Permanent neonatal diabetes mellitus: clinical presentation and epidemiology in Oman Archives of Disease in Childhood Fetal & Neonatal Volume 80(3), May 1999, pp 209F-212F

50. PNDM in Oman(2)

51. Thanks for your attention!!