Neuroprotection strategies in neonates with encephalopathyneokw.com/2nd-neokw/pdf/presentation/neuroprotection-Kuwait-talk … · Neuroprotection strategies in neonates with encephalopathy

Neuroprotection strategies in neonates with encephalopathy

Dr. Khorshid Mohammad, MD, MSc(Pediatrics), FABP, FRCP(Edin)

NICU lead, Neuro-Critical Care Program , University of Calgary

Disclosure

• I have no conflict of interest to disclose

Objectives

Problem identification

Define the Opportunity

Team Building-Managing change

Exploratory phase –

Build Understanding

Prepare for Future state

Education phase

Implementation-

Act to Improve

Analyze and sustain the change/Share learnings

• Brain injury of any type 5/1000 live birth

• HIE most common type in term and near term ,2.6/1000

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

Submitted for publication

Alberta

• 661,848 km²• Population : 4.146 million • 58000 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

Mortality and morbidity in Southern Alberta

0%

5%

10%

15%

20%

25%

30%

35%

40%

Any HIE Moderate to Severe HIE

11.6%16.1%

28%

35.1%

Mortality

CP or NDD

Acute brain injury in HIE

Objectives

Problem identification

Define the Opportunity

Team Building-Managing change

Exploratory phase –

Build Understanding

Prepare for Future state

Education phase

Implementation-

Act to Improve

Analyze and sustain the change/Share learnings

Video EEG and nurses

NNCC model in Calgary

NNCC initiative ( Jan 2014)

Pediatric NCC program (2016)

PICUNICU

Consultation model

• Before :

NNCC structure

Training program Clinical service

Research QI

NNCC

Objectives

Problem identification

Define the Opportunity

Team Building-Managing change

Exploratory phase –

Build Understanding

Prepare for Future state

Education phase

Implementation-

Act to Improve

Analyze and sustain the change/Share learnings

Prenatal risk factors

GABWSGALGA

PIH Hypertensi

onObesity

GDMDiabetes

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 1.39-7.004) and brain injury alone (OR 2.78; 95% CI 1.22-6.34)

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

Ventilation and hypocapnia

• 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 1.49-4.25;P=0.001)

Before After P value

Hypocarbia 70% 57% 0.03

Ventilation 62% 49% 0.029

Phosphate

outborn 66%

inborn 34%

HIE birth location (157)

Passive cooling and temperature control

Prediction model study

• Between 2006-20016

• 126 infants ≥35 weeks GA @ 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

Combined EEG and MRI as a prediction tool

Ab EEG and MRI

No Yes

CP or NDNo 19 24

Yes 0 8

Seizure at 1 yearNo 19 25

Yes 0 7

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%

Objectives

Problem identification

Define the Opportunity

Team Building-Managing change

Exploratory phase –

Build Understanding

Prepare for Future state

Education phase

Implementation-

Act to Improve

Analyze and sustain the change/Share learnings

Feb 2016

Hypoxic Ischemic Encephalopathy (HIE) – All Level Nurseries V 1.0

HE

MO

DY

NA

MIC

RE

SP

GL

UC

OS

E

AN

D F

LU

IDS

TH

ER

AP

EU

TIC

HY

PO

TH

ER

MIA

SE

IZU

RE

INF

EC

TIO

N

GOALManagement Pathway

Apnea, Cyanosis,

Tachypnea, Distress

Monitor SpO2

Send blood gas

Consider respiratory support

(invasive / noninvasive)

SpO2 90-95%

pCO2 45 - 55

mmHg

pH 7.3 - 7.4

Avoid:

Hypocapnea (60)

Hyperoxia

HR > 180 bpm, CRT > 3 sec

Pallor, Lactic acidosis,

Hypotensive (MAP < GA)

Evidence

of hypovolemia?

(abruption, subgleal

hemorrhage)

Consider Volume expanders

( NS or O Rh negative blood)

Consider inotropes

(following discussion with Neonatologist)

HR 80 - 160

MAP ≥ GA

Is glucose

< 2.6?

Start IV D10W at 60 mL/kg/d

Start IV D10W at 50 mL/kg/d

Monitor glucose

every 30 min

Is glucose

stabilizing?

Monitor glucose as appropriate

Give IV D10W bolus of 2 mL/kg

Glucose ≥ 2.6

Turn off radiant warmer

and unbundle infantAxillary temp (with

appropriate probe)

every 15 min OR

rectal continuous

monitoring

Is temp

< 33°C?

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

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

Is sepsis

suspected?

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

Ambient temp

25 - 26°C

Core temp

33 - 34°C

Seizure

control

Early antibiotics

administration

NO

YES

YES

NO

YES

NO

YES

YES

NO

Decision made for

cooling

NO

Avoid:

Severe hypothermia < 33°C

hyperthermia > 37°C

Objectives

Problem identification

Define the Opportunity

Team Building-Managing change

Exploratory phase –

Build Understanding

Prepare for Future state

Education phase

Implementation-

Act to Improve

Analyze and sustain the change/Share learnings

Provincial HIE clinical;

pathway project

Cooling calculator

Targeted neuro exam

teaching module

Tele medicine

Outreachprogram

Standard orders sts

Three methods of cooling on transport

Passive

39 babies

2013-2015

Gel packs

23 babies

2015-2016

Techotherm

9 babies2017

And then there is this!

DON'T POKE ME, I AM HIBERNATING!

NEUROPROTECTION PACKAGE FOR NEONATAL HIE

NNCC network

Objectives

Problem identification

Define the Opportunity

Team Building-Managing change

Exploratory phase –

Build Understanding

Prepare for Future state

Education phase

Implementation-

Act to Improve

Analyze and sustain the change/Share learnings

14%

10%

11%

23%

7%

14%

14%

3%

2%

0%

1 2 3 4 5 6 7 8 9 10

HIE Mortality

2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

N-NCC

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%

16%15%

9%

14%

9%

2010 2011 2012 2013 2014 2015

CNN

Hospital stay and cost (level III)

Before After P value

Level III NICU stay (mean) 10.24 8.15 0.004

Total NICU stay (mean) 13.89 9.69

Consistency of care

Before After

(25%-75%)IQ 6-13 5-10

NNCC and acute brain injury in HIE

62%

71%

52%

76%

44%

17%

36% 38%

29%18%

38%

52%

42%

59%

33%

17%21%

31%

5%7%

1 2 3 4 5 6 7 8 9 10

HIE MRI Severe abMRI

2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Before the training program

N=50

After the training program

N=50P value

Time from birth to Brain monitoring

initiation (hours) , Median (IQ)39(17-72) 7.5(4-12)

Seizure diagnosis and management

AED use

Clinical vs electrographic seizures

QI targeting inotropes

inotropes Dopamine Dobutamine Ns boluses

45%

27%

43%

55%

29%

22%19%

36%

before after

Trend over time

UCL

0.5783

CL 0.3693

LCL

0.1604

0.000

0.100

0.200

0.300

0.400

0.500

0.600

0.700

0.800

0.900

1.000

1 2 3 4 5 6 7 8 9 10

ino

tro

pes

%

Period

inotropes / total p Chart

Comparing the 3 methods of cooling

Passive Gel packs Techotherm

Reached target temp 54% 74% 100%

Maintained the temp within the target 26% 53% 100%

Time to target tem (min) 378 410 288

Temp fluctuation (mean) 1.5 1.7 0.6*

Highest temp (mean) 34.5 34.6 33.7*

Transport nurses feedback!

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

Clinical staging

• Moderate to Severe

EEG during cooling

28 electrographic seizures

MRI day 4

2.5 years

ACKNOWLEDGEMENTS

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 LangenbergerSANTS outreach program

team◦ Sumesh Thomas ◦ Renee Paul◦ NTNs and TRTs

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

Thank you!