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New Approaches for Newborns at Risk for

Brain Injury: Creation of the “NeuroNICU”

Krisa Van Meurs, MDRosemarie Hess Professor of Neonatal and Developmental Medicine

Stanford University School of Medicine

Medical Director, NeuroNICU

Lucile Packard Children’s Hospital Stanford

X Simpósio Internacional de Neonatologia do Rio de Janeiro

Hotel Royal Tulip, Rio de Janeiro

23 de Junho 2016

Why open a NeuroNICU ?

• Evolution in focus of NICU care: Improving neurologic and

neurodevelopmental outcomes

� Bringing new neurodiagnostic techniques and research findings

to the bedside

� Taking advantage of our local expertise in fetal medicine,

neonatal intensive care, neonatal neurology, pediatric

neuroradiology, pediatric neurosurgery, and high-risk infant

follow-up to focus on brain care

Survival to discharge for infants <29 weeks born in 2012 at

NICDH Neonatal Research Network Hospitals

0

10

20

30

40

50

60

70

80

90

100

22 23 24 25 26 27 28

Su

rviv

al

(%)

Gestational age (weeks)

Stoll BJ et al., JAMA 2015

EPICure 3-year outcomes: 2006 cohort

Moore T et al., BMJ 2012; 345:e7961

Survival has improved,

however outcome remains a challenge

Extremely low birth weight (ELBW) infant

Pre-ECMO and ECMO

Hypoxic ischemic encephalopathy (HIE)

Seizures

Inborn errors of metabolism

Meningitis/encephalitis

CNS malformations including Spina bifida

Congenital heart disease

Grade III/IV IVH with hydrocephalus

Why open a NeuroNICU ?

• Evolution in focus of NICU care: Improving neurologic and

neurodevelopmental outcomes

• Bringing new neurodiagnostic techniques and research findings

to the bedside

• Taking advantage of our local expertise in fetal medicine,

neonatal intensive care, neonatal neurology, pediatric

neuroradiology, pediatric neurosurgery, and high-risk infant

follow-up to focus on brain care

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What monitoring devices are used for sick neonates

in the NICU?

What about the brain?

Blood

pressure

End tidal

CO2

SaO2

Temperature

Heart

rate

Respiratory rate

Bedside brain monitoring

• A complimentary tool used at the bedside

• Used in conjunction with other neuroassessments and

diagnostics (e.g. neurologic exam, head ultrasound, CT, MRI)

• Provides bedside, unit-based clinicians with real-time

information about neurologic status

Bedside neuromonitoring devices

Continuous video

EEG (cEEG)

Amplitude integrated

EEG (aEEG)

Near infrared

Spectroscopy (NIRS)

Neurofax EEG,

Nihon Kohden Brainz BRM3, Natus INVOS 5100c, Covidien

Continuous video EEG

• Continuous, non-invasive, direct measure reflecting CNS function

• Electrode application and interpretation require expertise

• Can be viewed and interpreted remotely

• Demonstrates changes in brain function over time, evolution of

EEG pattern can be prognostic

• Gold standard for seizure detection because:

• 80-90% of neonatal seizures have no clinical correlate

• Seizure medications cause “uncoupling”

Amplitude integrated EEG (aEEG)

• Simplified EEG with small number of electrodes providing an overall

impression of cerebral activity.

• Raw EEG data is filtered, amplified, rectified and displayed in a time-

compressed semi-logarithmic fashion.

• Advantages of ease of use, minimal interference with care, and less training

required for interpretation.

Comparing EEG and aEEG

aEEG, 2 channels

3.5 hours

Conventional EEG, 16 channels

10 seconds

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aEEG interpretation by pattern recognition or voltage

Thoresen M, et al. Pediatrics (2010)

aEEG and prediction of outcome in

HIEPrior to cooling era:

Abnormal outcome is seen when

aEEG background does not

return to normal by 24 hours or

sleep wake cycles to not appear

by 36 hours.

In cooling era:

Abnormal outcome is seen when

aEEG background does not

normalize by 48 hours. Return of

SWC is more variable.

Thoresen M, et al. Pediatrics (2010)

Near infrared spectroscopy (NIRS)

• Continuous, real-time, non-invasive measure of regional tissue oxygenation

(rSO2)

• Able monitor cerebral, renal and mesenteric tissues

• Cerebral rSO2 is validated with jugular venous saturation

Use of cerebral oximetry in HIE

Lemmers P, et al. Ped Res (2013)

Cerebral saturation (rScO2) is higher and

fractional tissue oxygen extraction (FTOE)

is lower by 24 hours and onward in

neonates with HIE with adverse outcomes

FTOE = SaO2 – rScO2/SaO2

Reflects secondary energy failure with

reduced oxygen consumption by severely

injured neuronal cells

Solid line = good outcome

Dashed line = poor outcome

High rScO2 at 24 hours is associated

with poor neurodevelopmental outcomeClinical trials focusing on neurologic outcome

in the Packard NICU

Whole Body Hypothermia for HIE study 2000 Shankaran NICHD

Late Hypothermia study 2008 Laptook NICHD

Brain injury in WBH for HIE 2005 Barnes/Shankaran NICHD

Childhood outcomes of WBH for HIE 2010 Hintz NICHD

SUPPORT Neuroimaging study 2008 Hintz NICHD

SUPPORT Neuro School Age FU 2010 Hintz NICHD

Pilot Preemie aEEG study 2009 Davis/Van Meurs NICHD

Cerebral autoregulation with PDA 2011 Chock Internal

Short term ND outcome with CHD 2010 Chock, Heart Center

Optimizing Cooling Hypothermia Study 2011 Shankaran NICHD

Predicting Outcomes using aEEG 2011 Van Meurs BPCA

California Transport Cooling Trial 2012 Akula/Van Meurs Internal

Trial Name Year PI Funding

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Clinical research results reach the bedside for babies with

hypoxic ischemic encephalopathy (HIE)

Therapeutic hypothermia with lowering of body temperature to 33-

34°C within 6 hours after birth in newborns ≥36 weeks gestation with

moderate to severe HIE reduces the risk of death or major

neurodevelopmental impairment at 18 months.

Why open a NeuroNICU ?

• Evolution in focus of NICU care: Improving neurologic and

neurodevelopmental outcomes

• Bringing new neurodiagnostic techniques and research findings

to the bedside

• Taking advantage of our local expertise in fetal medicine,

neonatal intensive care, neonatal neurology, pediatric

neuroradiology, pediatric neurosurgery, and high-risk infant

follow-up to focus on brain care

The Neuro NICU is multi-disciplinary

Child Neurology

Developmental Behavioral Pediatrics/

High Risk Infant follow-up Clinic

Developmental

Team

Pediatric Neurosurgery

Child Psychiatry

Neonatology

Neuroradiology

Learning from other Neuro NICUs

UCSF NeuroIntensive Care Nursery –2007

Phoenix Children’s NeuroNICU – 2009Johns Hopkins

St. Louis Children’s Hospital

Vanderbilt Medical Center

Children’s National Medical Center, Washington D.C.

Boston Children’s - Pediatric Neuro ICU

Glass H, et al. Neurocrit Care (2010)

Our NeuroNICU Journey

Jan 2012 Multidisciplinary meeting to discuss the concept

June 2012 Written proposal and budget submitted

Oct 2012 Funding approved

Dec 2012 Hired NeuroNICU Program Consultant

Feb/March 40 RNs trained as NeuroNICU RNs in 3-day training

2013 Hands-on sessions for hypothermia, NIRS and aEEG

April 2013 Opening of the NeuroNICU

April 2014 1 year anniversary – 226 patients cared for

Jan 2015 Training course with 130 participants

April 2015 2 year anniversary – 581 patients

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NeuroNICU Core Team Members

Medical Director Krisa Van Meurs, MD

Neurology Director Courtney Wusthoff, MD MS Epi

Associate Directors Valerie Chock, MD MS Epi

Sonia Bonifacio, MD

Program Consultant Kathi Randall, RN NNP CNS

Clinical Nurse Specialist Shannon Tinkler, BSN

NeuroNICU NNP Leads Celia Glennon, NNP RN

Rachael Small, NNP RN

Fellow liaison Anca Pasca, MD

• Weekly meeting of core team members

• Monthly meeting of larger group including OT, PT, social work, parent rep, fellow

liaison, nurses, assistant nurse managers, research team

Clinical service

� Specialized care by Neuro NICU trained RN team (n=90)

� Daily joint rounds with Neurology service

� On-site NNP or educator 5 days a week

� Patients with neuro issues or at risk for neurologic injury

� EPIC enhancements: Neuro NICU tab, dot phrases for neuro exam and aEEG interpretation, order sets for hypothermia and seizures

� Neuro NICU database in REDCap for research, QA/QI, and program planning

Top 12 priority diagnoses for Neuro NICU

Priority DiagnosisExpected LOS in

NNICU (days)Monitoring

Neurology

consult

1 HIE/cooling 7-10 aEEG/cEEG & NIRS Yes

2 Seizures 7 aEEG/cEEG Yes

3 ECMO/pre-ECMO 7 NIRS + aEEG PRN

4 Critical/unstable 7 NIRS & consider aEEG PRN

5 Preemie <29 weeks 7-10 NIRS PRN

6 Grade III/IV or hydrocephalus 7 aEEG/cEEG Yes

7 Metabolic disease 7 aEEG/cEEG PRN

8CNS anomalies/Primary neurologic

disorders7 aEEG/cEEG Yes

9 Cyanotic CHD 7 NIRS PRN

10 CNS infection 7 aEEG/cEEG Yes

11 Symptomatic PDA 7 NIRS PRN

12 ALTE 3 aEEG PRN

NeuroNICU Education

Initial education

• 2-3 day course

Weekly

• “5 minute Friday” and Perinatal conference

Ongoing

• Online video lectures, slides, and quizzes to review aEEG and NIRS

theory and interpretation

• Annual skills day (e.g. aEEG, NIRS, neuro exam, positioning,

hypothermia equipment and protocol review)

NeuroNICU Training Course

� 2-3 day course, 25 lectures by 20 speakers and hands-on sessions

� Topics include: Fetal and neonatal brain development IVH and white matter injuries Neonatal neuroimaging HIESeizure management NIRS and aEEGPalliative careFollow-up clinic and beyondParent’s perspective

� Audience includes NeuroNICU RNs, NNPs, hospitalists, neonatal fellows, neonatologists, OT, PT, Developmental Care team, and follow-up clinic staff

And extends across the continuum of care

• Prior to birth (Fetal Service)

• From admission to discharge

• From discharge to home

• From home to follow-up

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A Neuro-Conscious NICU:

Connecting Research to Nursing Practice

• Kathi Randall, RN, MSN, CNS, NNP-BC

• LPCH NeuroNICU Consultant

Asse

ssm

en

t

Ima

gin

g

Mo

nito

ring

Pro

tectio

n4 Pillars of Neuro-NICU Care

The Neuro-Conscious NICU

• Neuro-Assessment

– Identification of Risk

– Clinical/Hands On

– Metabolic

– Follow Up Care

• Neuro-Imaging

– MRI

– MRS

– Ultrasound

• Neuro-Protection

– Developmental Care

– Cooling

– Medications

– Nutrition

– Adjunctive

• Neuro-Monitoring

– EEG

– aEEG

– NIRS

– Hearing Screen

How do we assess the brain?

Neuro-Assessment

Training included detailed neonatal neuro exam, Sarnat, and

Neonatal Pain, agitation, and sedation Scale (N-PASS)

Neuro-Imaging

Training included types, timing and indications for

neuro-imaging as well as prognostic implications

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Neuro-Monitoring

Theory and practice

� aEEG application techniques and

interpretation

� Near infrared spectroscopy (NIRS) and

Vital Sync for autoregulation

� Conventional EEG interpretation for the

non-neurophysiologist

Neuro-Protection

� Initially used to characterize substances or strategies capable

of preventing cell death

� Now, encompasses all interventions that promote normal

development and prevent disabilities

What A Nurse Ought To Do

“(Although) Nursing has been limited to

signify little more than the administration

of medicines…..It ought to signify the

proper use of air, light, warmth,

cleanliness, quiet, and the administration

of diet.”Florence Nightingale, 1859

Nightingale, Florence (1859). Notes on Nursing: What it is, and what it is not.. Philadelphia: Edward Stern & Co..

Florence’s Environment of Care

The impact of the environment on a wounded

individual’s ability to heal is undeniable.

A Developmentally Supportive Environment

� Create a balance of medically intense care with

supportive, nurturing, developmentally supportive

care

� Does not replicate the intrauterine environment but

simulates it in order to minimize the negative impact

of the NICU environment

Integrative Model of Developmental Care

• Safeguarding sleep

• Optimizing nutrition

• Minimizing stress and pain

• Protecting skin

• Positioning and handling

• Partnering with families

Smell, sound, touch, temperature, light

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Potentially better practices to prevent brain injury in

VLBW infants

1. Antenatal betamethasone

2. Optimize peripartum management and delivery at a center with a NICU

3. Direct management by Neonatologists/NNPs

4. Minimize pain and stress

1. Avoid early LP

2. Developmental Care

5. Optimal Positioning (Mid-line)

6. Treat hypotension (Keep MAP > 30 not GA)

7. Limit postnatal indomethacin use

8. Optimize respiratory support

9. Limit sodium bicarbonate use

10.Use post-natal dexamethasone judiciously (>42 days & too early)

Carteaux P, Pediatrics (2003)

Maintain Midline Head Position x 72 hours

Essential elements of positioning

� Containment with boundaries

All 360 degrees

Not restrictive

The right size for the baby

� Promote flexion/prevent extension

� Midline

Nose, nipples, knees and toes

Infant Positioning Assessment Tool (IPAT)

Indicator 0 1 2

Shoulders

Hands

Hips

Knees, ankles, feet

Head

Neck

Max Score = 12

Coaghlin M, et al. Newborn and Infant Nursing Reviews (2010)

Prevention of Typical Complications

• Mounting Evidence for Infection and

Inflammation and it’s impact on brain

development

• Rethink other NICU programs as Neuro-protective

– NEC Prevention

– Sepsis Prevention

– Ventilator-Induced Brain Injury

Kolan, J of Child Neuro, 2014

Yu, JAMA, 2013

Effects of hypocarbia and hypercarbia

Granot S, Ped Neurol (2012)

Multiple studies have associated hypocarbia in VLBW infant with cerebral palsy and PVL.Levene M. Arch Dis (2007)

Both minimum PCO2 and cumulative CO2<35 were associated with poor outcome in HIE (p<0.05). Pappas A, et al. J Pediatr (2011)

Higher PaCO2 was an independent predictor of severe IVH/death, BPD/death, NDI/death.Ambalavanan N, et al. Arch Dis Child Fetal Neonatal Ed (2015)

24 week infant with PaCO2 105 then 44

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UAC blood sampling practices

Lott JW, et al. J Perinatol (1996)

Schulz G, et al. Pediatrics (2003)

Rapid withdrawal and flushing of

catheters in the aorta can affect cerebral blood

flow velocity, volume and oxygenation. Altered cerebral

blood flow has been correlated with IVH and PVL.

Blood sampling from UAC produces significant changes

in cerebral blood flow velocity as measured using doppler

in anterior cerebral artery.

Withdrawal -19%

Infusion +9% change

NIRS and tissue oxygen extraction(TOI) were measured

with 2.3 ml blood withdrawal over 20 and 40 seconds.

20 seconds Significant change

40 seconds No change

Therapeutic hypothermia for HIE

� Both body and head cooling

have been shown to reduce

death and neuro-

developmental impairment

(RR 0.75 95% CI 0.68-0.83 )

and NNT = 7

Identification and Treatment of Seizures

• Seizures can accelerate cell death in HI injuries and adversely affect neurogenesis in animal models.

• In term newborns with HIE, seizures

on EEG are associated with higher

mortality and disability at 19 mons. Wyatt JS, et al. Pediatrics (2007)

• Preterms with seizures on EEG

during the first days of life have

worse neurodevelopmental

outcomes. Shah DK, et al. Pediatr Res (2010),

Vesoulis ZA, et al. Pediatr Res (2014)

Kangaroo Care improves brain outcomes and more

Kangaroo mother care is associated

with:

• Reduction in mortality (RR 0.68

95% CI 0.48-0.96)

• Reduction in nosocomial infection

(RR 0.42 95% CI 0.24-0.73)

• Increased weight, length and head

circumference gain

• Improved Bayley MDI (p=0.03) and

PDI (p=0.06) at 1 year

Conde-Agudelo A. et al. Cochrane Database of Systematic Reviews (2011)

Ohgi S, et al. J Perinatol (2002)

Parental Provided Massage PREVENT Pain and Stress in the NICU

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Balance SENSORY Experiences 2 Different Bathing Experiences

Create bonds that will last a life-time Why a Neuro-NICU?

� Brain injury is a reality of many infants in the NICU.

� The brain is the organ that has the greatest impact on long

term quality of life and function.

� We have the opportunity to improve the quality of life of high-

risk infants, and the quality of care provided through the

expansion of new technologies, therapies, and practices.

� Early and more aggressive treatment of neonatal brain

pathology will not only result in better survival but better

neuro-developmental outcomes.

� Foster an early and strong relationship between family and

child, as well as with teams that will be providing long-term

management and care

Neuro-conscious care is a new frontier for NICUs

We have their futures in our hands

Thank you!