Neuroprotection strategies in neonates with

Transcription

1 Neuroprotection strategies in neonates with encephalopathy Dr. Khorshid Mohammad, MD, MSc(Pediatrics), FABP, FRCP(Edin) NICU lead, Neuro-Critical Care Program, University of Calgary

2 Disclosure I have no conflict of interest to disclose

3 Objectives Analyze and sustain the change/share learnings Implementation- Act to Improve Prepare for Future state Education phase Exploratory phase Build Understanding Team Building- Managing change Problem identification Define the Opportunity

4 Brain injury of any type 5/1000 live birth HIE most common type in term and near term,2.6/1000

5 Hospital-related, maternal, and fetal risk factors for neonatal asphyxia: A 15 year retrospective cohort study in Alberta, Canada Submitted for publication

6 Alberta 661,848 km² Population : million birth per year Southern Alberta Neonatal Transport Service (SANTS): serves a catchment area of 1.8 million people and more than 20,000 births/year TH was introduced as standard of care in June 2008 Approximately 40 neonates eligible for TH get admitted to Calgary centers per year

7 Mortality and morbidity in Southern Alberta 40% 35% 30% 25% 20% 28% 35.1% Mortality CP or NDD 15% 10% 5% 11.6% 16.1% 0% Any HIE Moderate to Severe HIE

8 Acute brain injury in HIE

9 Objectives Analyze and sustain the change/share learnings Implementation- Act to Improve Prepare for Future state Education phase Exploratory phase Build Understanding Team Building- Managing change Problem identification Define the Opportunity

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11 Video EEG and nurses

12 NNCC model in Calgary NNCC initiative ( Jan 2014) Pediatric NCC program (2016) NICU PICU

13 Before : Consultation model

14 NNCC structure Training program Clinical service NNCC Research QI

15 Objectives Analyze and sustain the change/share learnings Implementation- Act to Improve Prepare for Future state Education phase Exploratory phase Build Understanding Team Building- Managing change Problem identification Define the Opportunity

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17 Prenatal risk factors GA BW SGA LGA PIH Hypertensi on Obesity GDM Diabetes

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19 Use of inotropes and Brain injury Use of inotropes in the first 72 hours associated with significant increase in the risk of death or brain injury (OR 3.11; 95% CI ) and brain injury alone (OR 2.78; 95% CI ) Adjusted for gestational age (GA), birth weight, birth outside the referral tertiary centre, cord blood gas ph, Apgar score at 10 minutes of age, HIE clinical stage, use of anti-seizure medication, use of sedation, and TH

20 Ventilation and hypocapnia Before After P value Hypocarbia 70% 57% 0.03 Ventilation 62% 49% Infants with hypocapnia had significantly higher HIE changes on MRI and increased the odds of abnormal MRI after adjusting for HIE clinical severity ( AOR 2.51, CI ;P=0.001)

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22 Phosphate

23 HIE birth location (157) inborn 34% outborn 66%

24 Passive cooling and temperature control

25 Prediction model study Between infants 35 weeks birth with mild HIE 86 cases had available MRI data 71 cases with available EEG 95 cases with available 1 year seizure outcome 95 cases with available neurodevelopmental outcome

26 Combined EEG and MRI as a prediction tool Ab EEG and MRI No Yes CP or ND Seizure at 1 year No Yes 0 8 No Yes 0 7

27 Combining clinical, EEG, and MRI PPV in predicting abnormal ND was 26%, NPV 100% PPV in predicting seizure at 1 yr was 22%, NPV 100%

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29 Objectives Analyze and sustain the change/share learnings Implementation- Act to Improve Prepare for Future state Education phase Exploratory phase Build Understanding Team Building- Managing change Problem identification Define the Opportunity

30 Feb 2016

31 INFECTION SEIZURE THERAPEUTIC HYPOTHERMIA GLUCOSE AND FLUIDS HEMO DYNAMIC RESP Hypoxic Ischemic Encephalopathy (HIE) All Level Nurseries V 1.0 Management Pathway GOAL Apnea, Cyanosis, Tachypnea, Distress Monitor SpO2 Send blood gas Consider respiratory support (invasive / noninvasive) Avoid: Hypocapnea (<35) Hypercapnea (>60) Hyperoxia SpO % pco mmhg ph HR > 180 bpm, CRT > 3 sec Pallor, Lactic acidosis, Hypotensive (MAP < GA) Evidence of hypovolemia? (abruption, subgleal hemorrhage) YES NO Consider Volume expanders ( NS or O Rh negative blood) Consider inotropes (following discussion with Neonatologist) HR MAP GA Is glucose < 2.6? YES Start IV D10W at 60 ml/kg/d Monitor glucose every 30 min Is glucose stabilizing? YES Monitor glucose as appropriate Glucose 2.6 NO Start IV D10W at 50 ml/kg/d NO Give IV D10W bolus of 2 ml/kg Decision made for cooling Turn off radiant warmer and unbundle infant Avoid: Severe hypothermia < 33 C hyperthermia > 37 C Axillary temp (with appropriate probe) every 15 min OR rectal continuous monitoring Is temp < 33 C? YES NO Put hat & light blanket on infant. Recheck temp; if remains low, turn on warmer to 0.5 C above infant s temp Monitor Temp every 30 min to continue following protocol Ambient temp C Core temp C Abnormal, rhythmic movements not suppressed by holding; Eye deviation /staring /flickering; Sudden, abrupt movements (myoclonus) + vital sign changes (desat, apnea, tachycardia, or hypertension) 1. Maintain ABC 2. Give phenobarbital IV 20 mg/kg/d 3. Consult Neonatologist If seizures persist: Give another dose phenobarbital IV 20 mg/kg/d after discussion with Neonatologist Seizure control YES Is sepsis suspected? NO Draw: blood culture and CSF culture (if meningitis suspected and baby is stable) Monitor clinically for signs/symptoms of sepsis Start: Ampicillin IV 50 mg/kg/dose (increase to 100 mg/kg if meningitis suspected) and Cefotaxime IV 50 mg/kg/dose Consult local monographs if repeated doses required before Transport Team arrives Early antibiotics administration

32 Objectives Analyze and sustain the change/share learnings Implementation- Act to Improve Prepare for Future state Education phase Exploratory phase Build Understanding Team Building- Managing change Problem identification Define the Opportunity

33 Outreach program Standard orders sts Cooling calculator Provincial HIE clinical; pathway project Targeted neuro exam teaching module Tele medicine

34 Three methods of cooling on transport Passive 39 babies Gel packs 23 babies 2017 Techotherm 9 babies

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36 And then there is this!

37 NEUROPROTECTION PACKAGE FOR NEONATAL HIE DON'T POKE ME, I AM HIBERNATING!

38 NNCC network

39 Objectives Analyze and sustain the change/share learnings Implementation- Act to Improve Prepare for Future state Education phase Exploratory phase Build Understanding Team Building- Managing change Problem identification Define the Opportunity

40 HIE Mortality 23% N-NCC 14% 14% 14% 11% 10% 7% 3% 2% 0%

41 Mortality in the literature and Canadian Neonatal network (CNN) Mortality was 28% in cooling group compared 43% in the standard group in the most recent meta-analysis 23% CNN 16% 15% 14% 9% 9%

42 Hospital stay and cost (level III) Before After P value Level III NICU stay (mean) Total NICU stay (mean) <0.001 Transfer back (%) 42% 22% <0.001

43 Consistency of care Before After (25%-75%)IQ

44 NNCC and acute brain injury in HIE HIE MRI Severe abmri 71% 76% 62% 38% 52% 52% 42% 59% 44% 33% 17% 36% 38% 31% 21% 29% 18% 5% 7%

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47 Before the training program N=50 After the training program N=50 P value Time from birth to Brain monitoring initiation (hours), Median (IQ) 39(17-72) 7.5(4-12) <0.001 Clinical seizures, N (%) 36(72%) 25(50%) Electrographic seizures, N (%) 10(20%) 17(34%) 0.11 Clinically misdiagnosed seizures, N (%) (in infants with no electrographic seizures) Number of routine EEG done/patient, Median (IQ) Maintenance Anti- seizures on discharge, N (%) Anti-seizure medication burden (mg/kg/infant), Mean (SD) 26/40(65%) 12/33(33%) (2-3) 1(1-2) (38%) 11(22%) (347) 95(85) 0.45

48 Seizure diagnosis and management

49 AED use

50 Clinical vs electrographic seizures

51 QI targeting inotropes before after 55% 45% 29% 27% 22% 43% 19% 36% inotropes Dopamine Dobutamine Ns boluses

52 inotropes % Trend over time inotropes / total p Chart UCL CL LCL Period

53 Comparing the 3 methods of cooling Passive Gel packs Techother m Reached target temp 54% 74% 100% Maintained the temp within the target 26% 53% 100% Time to target tem (min) Temp fluctuation (mean) * Highest temp (mean) * Transport nurses feedback!

54 Baby T girl 38 weeks, AGA, outborn, FHD Apgar 1,1,4, and 5 Cord ph: 6.88 Severe hypotension ( NS, O- blood, inotropes) Ventilated for 6 days, severe hypocapnia ( lowest 23) Hypoglycemia

55 Moderate to Severe Clinical staging

56 EEG during cooling

57 28 electrographic seizures

58 MRI day 4

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60 2.5 years

61 ACKNOWLEDGEMENTS Pediatric-NCC Michael Esser Luis Bello-Espinoza Jeffrey Buchhalter JP Appendino Aleksandra Mineyko Jong Rho Adam Kirton Harvey Sarnat Alice Ho Kim Smyth Xing-Chang Wei James Scott Megan Crone NICU-NCC Alixe Howlett Hussein Zein Prashanth Murthy Thierry Lacaze Leonora Hendson Elsa Fiedrich Ayman Abou Mehrem Ipsita Goswami Jan Lind Cathy Metcalf Leigh Irvine Norma Oliver Shauna Langenberger SANTS outreach program team Sumesh Thomas Renee Paul NTNs and TRTs

62 Thank you!