1. NICU MORTALITY

2. Objectives Emphasize the importance of adequate communication between medical teams, regular and proper evaluation of adequacy of resuscitation Present the Therapeutic Hypothermia Protocol according to the Journal of Clinical Neonatology

3. R.V. Term Baby Boy NSD 35 y.o. G2P2 (2002) 39 3/7 weeks AOG Anthropometrics: – BW 3120g, BL 53cm, HC 34cm, CC 31cm, AC 30cm – AGA Apgar score: 0, 0, 1, 1, 1

4. Maternal History Regular prenatal check-up Regular intake of multivitamins Ultrasound – unremarkable Congenital anomaly scan – normal Normal OGCT No BP elevations CBC and UA upon admission – normal

5. Past Medical History No hypertension, no DM Family History (+) hypertension, DM, heart disease, colon CA Personal/Social History Occasional alcoholic beverage drinker, nonsmoker, no use of illicit drugs

6. OB History G1 – 2009 – NSD, full term male, no fetomaternal complications G2 – present pregnancy

7. Admitting CTG: 3hrs 30mins prior to delivery Baseline 130 - 135bpm, with accelerations, no decelerations, good fetal movement, strong contractions every 8 mins

8. After CEA: 3hrs prior to delivery Baseline 140 bpm, with accelerations, no decelerations, good fetal movement, strong contractions every 8 mins

9. After AROM: 2hrs 30mins prior to delivery Baseline 135 to 140 bpm, moderate variability, with accelerations, with variable decelerations as low as 60 bpm with slow recovery, with moderate to strong uterine contractions every 3-4 minutes

10. 1hr and 30mins prior to delivery Baseline 135 to 140 bpm, moderate variability, with accelerations, with variable decelerations as low as 70 bpm with slow recovery, with moderate to strong uterine contractions every 2-3 minutes

11. Prior to transfer to DR: 1hr prior to delivery Baseline 130-135 bpm, moderate variability, no accelerations, with variable decelerations as low as 60 bpm with slow recovery, with moderate to strong uterine contractions every 3-4 minutes

12. FHT tracing at DR (supine) Change in baseline 120 bpm, moderate variability, no accelerations, with variable decelerations as low as 50 bpm with slow recovery

13. Tracing at DR (Left lateral decub): 40mins prior to delivery Maternal heart tone

14. Upon delivery Pale, not breathing, limp Drying and stimulation 30s Limp, pale, not breathing, HR 0 Positive pressure ventilation

15. APGAR Score 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 1 0 0 1 0 0 0 0 0 1 1 39 2/7

16. 20 mins Limp, pale, not breathing, HR 50s ET tube placement reevaluated ET tube reinserted 25 mins Limp, pale, not breathing, HR 180s NICU Transfer

17. At the NICU Pale, unresponsive BP not appreciated, HR 180, on bag-tube ventilation, T 34C No dysmorphic features Pupils 8-9mm dilated, not reactive to light No spontaneous breathing, Equal chest rise, good air entry both lungs Regular cardiac rhythm, no murmur appreciated Soft abdomen Poor pulses, CRT prolonged

18. Severe Hypoxic-Ischemic Encephalopathy, post cardiopulmonary arrest Initial assessment

19. Problems Asphyxia Mixed Metabolic and Respiratory Acidosis, Intractable 15 mins of lifeVBG (Bag tube vent at 10lpm) pH6.604 C0261.2 PO2114.5 HCO36.1 BE-30 O2 sat82.9% Mixed metabolic and respiratory acidosis Correction with NaHCO3 Therapeutic Hypothermia VBG (MV settings: Fi02 100, iT 0.5 FR 10 PIP 26 PEEP 50 RR 50) 6.52 95.6 79 7.8 -30 60% Mixed met and resp acidosis Hooked to MV Lactate (4.5-19.82 mg/dL) 223.2 mg/dL

20. Problems Shock prob cardiogenic Severe anemia prob sec to hemorrhage HgbHctWBCBandNeutLymphMonoPlt 572042.764541818870 nRBC Cranial Ultrasound Normal PT Control13.3 Patient38.5 % activity0.2 INR3.78 aPTT Control29.3 Patient138 2D Echo PA pressure 50 Right to left shunting (PDA) Underfilled left ventricle Severe tricuspid regurgitation PFO bidirectional PNSS 20mL/kg bolus 2x Dopamine and Dobutamine Drip Blood transfusion ordered but refused PNSS 20mL/kg bolus 2x Dopamine and Dobutamine Drip Blood transfusion ordered but refused

21. Problems Infection HgbHctWBCBandNeutLymphMonoPlt 572042.764541818870 nRBC Blood culure and sensitivity No growth CRP (NV 0-0.5mg/dL) 0.01mg/dL Ampicillin 50mg/kg/dose Gentamicin 4mg/kg/day Ampicillin 50mg/kg/dose Gentamicin 4mg/kg/day

22. 10hrs and 30 mins Patient expired 10 th hour of life Still unresponsive On mechanical ventilator On Dopamine and Dobutamine Drip DNR signed

23. INTRACTABLE METABOLIC ACIDOSIS SECONDARY TO MULTIORGAN DYSFUNCTION SECONDARY TO PERINATAL ASPHYXIA Final Diagnosis

24. Learning Points Adequate communication between teams Regular and proper evaluation of adequacy of resuscitation

25. THANK YOU!!!

26. DISCUSSION

27. Perinatal Asphyxia Condition of impaired gas exchange that leads to fetal hypoxemia and hypercarbia Occurs during the 1 st and 2 nd stage of labor In term infants, 90% occur in antepartum or intrapartum period as a result of impaired gas exchange across the pacenta Postpartum – secondary to pulmonary, cardiovascular, neurologic abnormalities Cloherty J. Manual of Neonatal care, 6 th ed

28. Hypoxic-Ischemic Encephalopathy Abnormal neurobehavioral state in which the predominant pathogenic mechanism is impaired cerebral blood flow Suspected if: – AS 5minutes – FHR <60 bpm – Prolonged (>1hr) acidosis – Seizures within the first 24-48hrs after birth – Burst-suppression patten EEG 20-30% of infants die in the neonatal period Cloherty J. Manual of Neonatal care, Lippincott Williams and Wilkins, 6 th ed. 2008 p89 Kliegman R. et al. Nelson Textbook of Pediatrics, 19 th Ed. 2011 p571

29. Sarnat and Sarnat Staging for HIE

30. Diagnostic Imaging Diffusion-weighted MRI Kliegman R. et al. Nelson Textbook of Pediatrics, 19 th Ed. 2011 p571

31. Treatment Therapeutic hypothermia – decreases the rate of apoptosis and suppresses production of mediators known to be neurotoxic, including extracellular glutamate, free radicals, nitric oxide, and lactate. Kliegman R. et al. Nelson Textbook of Pediatrics, 19 th Ed. 2011 p571

32. Therapeutic Hypothermia >= 36 weeks AOG – Physiological criteria Evidence of intrapartum hypoxia, including at least two of the following: – 1.Apgar score 5 or less at 10 min – 2. Needing mechanical ventilation and/or ongoingresuscitation at 10 min – 3. Metabolic or mixed acidosis defined as arterial cord gas, or any blood gas within the first hour of life showing pH of 7 or less, or base deficit of ≥12 mmol/l Mosalli R. Whole body cooling for infants with hypoxic-ischemic encephalopathy. J Clin Neonatol 2012;1:101-6.

33. Neurological criteria – One of the following: Seizures is an automatic inclusion Evidence of encephalopathy suggested a-EEG Physical examination consistent with moderate to severe encephalopathy Therapeutic Hypothermia Mosalli R. Whole body cooling for infants with hypoxic-ischemic encephalopathy. J Clin Neonatol 2012;1:101-6.

35. Infants not Eligible for Cooling Birth weight less than 2000 g Gestational age less than 36 weeks Inability to initiate cooling by 6 h of age Clinical coagulopathy Life-threatening abnormalities of the cardiovascular or respiratory systems such as complex congenital heart disease and PPHN Major congenital malformations, imperforate anus, suspected neuromuscular disorders, or presence of known lethal chromosomal anomaly Death appears inevitable Mosalli R. Whole body cooling for infants with hypoxic-ischemic encephalopathy. J Clin Neonatol 2012;1:101-6.

36. PROTOCOL

38. Specific Supportive Treatment during Hypothermia Respiratory support – assisted ventilation, keep 02 at 92-98% Cardiovascular support – asymptomatic sinus bradycardia without cardiac dysfunction – At 33.5°C, the average HR is 80–100 beats per minute bpm – If inotropic support is required, the following regime is suggested: Dopamine up to 10 mg/kg/min If still hypotensive add dobutamine up to10 mg/kg/min

39. Fluids – Start with 50–60 ml/kg/day – insert urinary catheter to measure urine output Electrolytes – Na and Cl levels could fall duet o increased renal loss in hypothermia Coagulation – mild derangement of blood viscosity and coagulation Specific Supportive Treatment during Hypothermia

40. Rewarming Procedure increase the rectal temperature to 36.5–37°C at a rate not to exceed 0.5°C per hour. final temperature goal is 36.5°C and should take about 7 hrs to achieve.

41. Prognosis Infants with initial cord or initial blood pH <6.7 – 90% risk for death or severe neurodevelopmental impairment at 18 mo of age. Apgar scores of 0-3 at 5 min, high base deficit (>20-25 mmol/L), decerebrate posture, and lack of spontaneous activity are also at increased risk for death or impairment.

42. Thank you!