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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!