Patrick McNamara

Associate Professor of Pediatrics

Associate Scientist

Enhancing Management of Circulatory Instability in Neonates

The Vulnerable Neonate

How will you ensure cardiovascular stability?

Myths

&

Magical numbers

&

Cook books

Metabolic Homeostasis

Cellular Metabolism

Oxygen Delivery

HemoglobinAnemia

Hemorrhage

Oxygen SaturationLung disease

Shunts

Cardiac OutputHeart Ratearrhythmia

PreloadVolume status

Diastolic functionPericardial effusion

ContractilityCatecholamines, sepsis

Cardiomyopathy, acidosis

AfterloadSVR, pericardial “P”

BP

SVR

Oxygen Consumption

Basal MetabolismPain, sedation, anxiety

thermogenesis

WorkBreathing, growth, trauma

catabolism, fever

Cost-effectiveness

Optimal Outcome

The Changing NICU

What is Targeted Neonatal Echocardiography?

• Extension of the clinical examination - not confined to organs (Assessment phase)– Hemodynamics, Organs, Catheters– Ductal evaluation, Pulmonary hemodynamics, LV performance

• Relate physiologic and hemodynamic data to the clinical problem (Integration phase)

• Focused clinical decision making

• Response to intervention (Response)

Scenario I

• 19 day old male, born at 24 weeks gestation (650 gms), with a large HSDA (3.2 mm) referred for surgical ligation (failed 2 courses of indomethacin)

• E Coli sepsis, bilateral IVH

• Lung disease: HFOV 9 cm H20, FiO2 0.4

• Uneventful procedure (52 mins duration)

Blood Pressure

Time [hrs]

0 5 10 15 20 25 30

BP [m

mHg

]

10

20

30

40

50

60

70

Dobut.

5 mcg/kg/minDobut. 10

Dobut.20

0 1 4 8 10 20 26Heart rate 163 159 150 155 160 159 151

FiO2 0.25 0.3 0.25 0.31 0.3 0.35 0.35

MAP 7.6 8.1 6.7 7 7.6 8 9.8

pH 7.37 7.36 7.26 7.14 7.21

LAC 1.0 1.7 2.6 5.4 3.6

IssuesProblem: Systemic hypotension & low output

state secondary to LV dysfunction and mechanical compression effects of extra-cardiac effusion

Issue: :• Reason for clinical deterioration different

from presumed physiology• Potential for cardiorespiratory arrest high

without timely and appropriate intervention

Scenario II• 40 week male, 3.3 kg with antenatal diagnosis of

CDH & suspected aortic arch hypoplasia

• Severe oxygenation failure from birth

• Prostaglandin infusion (0.05) commenced

• No response to inhaled Nitric Oxide

• Postnatal echo equivocal

PGE1 iNO Dopamine Epinephrine Milrinone, wean PGE1/pressors

0.01 20ppm 15 µg/kg/min 0.03 mg/kg/mi 0.66 mg/kg/min

BP 31/23 (26) 43/30 (35) 39/30 (34) 43/32 (35) 56/32 (46)

HR 182 194 186 193 161

Lactate 2.8 5.5 7.2 7.9 1.3

U.O. (mls/kg/hr) 0.75 4.2

4hrs 12hrs 24 hrs 36hrs

Issues:Problem: Low systemic blood flow 2° to hyperinotropy and

excessive L-R transductal shunting

Danger: Complication of therapy• Cardiotropic agents (e.g. dopamine, epinephrine) which

increase myocardial contractility → impair diastolic performance and low cardiac output state.

• Pressor agents further exacerbate the transductal shunt → low cardiac output state

Impact: Functional USS may help identify to origin of the low output state (e.g. myocardial dysfunction, transductalshunting) facilitating the choice of cardiotropic agent(pressor vs vasodilator)

Merits of TnECHO

• Provides timely hemodynamic information to confirm or question the presumed pathophysiology

• Earlier identification of “neonatal disease” e.g. HSDA, pericardial effusion, CHD

• Delineates “need” for treatment and assists with selection of “desirable therapy” e.g. iNO or cardiotrope, vasodilator or vasopressor

• Facilitates monitoring the response to therapySeghal & McNamara 2008

Emergence of Point of Care USS

•1950-60s: 1st ultrasound equipment, restricted use: not portable

• 1970s: Cranial USS performed by neonatologists in Europe, Australasia

Levene 1982 Arch Dis Child

• Echo performed by radiology until late 1970s (TURF War I)

•Point of Care ultrasound used by adult intensivists, OBG nurses (hemorrhage, fetal well-being), ER physician (abominal aneurysm) & surgeons (acute abdomen, scrotum)

Australasian Society for Ultrasound Certificate in Clinician performed USS

Evans 2000 – Survey of neonatal fECHO practice in ANZAC

Ward 2001 – Errors in neonatal echo in ANZAC

2009 PAS, AAP workshops in fECHO

2010 Canadian fECHO Network40% centers with trained neonatologist

2007 CCPU, Australasia

2003 Toronto – fECHO in clinical care

Pre-2000 – Ad-hoc fECHO practice in ANZAC, UK & Europe

2005 Toronto – fECHO training program

2005 RCPCH, UK fECHO manadatedfor tertiary level neonatologists

ECHO in the NICU, ASE writing group

Clinical question by neonatologist

Ultrasound performed by technician

Image interpretation

Report generation

Traditional Echocardiography Model

Issues• Disconnect between clinical question and study

interpretation

• Information missing with need for repeat of study

• Temporal delay in acquisition of information

• Limited ability to perform sequential studies

• Out-of-hours studies limited to cases where likelihood of CHD high

Refining Therapeutic Decision-Making

Clinical Problem

Functional Evaluation

Hemodynamic Problem Anatomic Problem

Medical decision Cardiology

Consultation

TnECHO - Indications• Is their a hemodynamically significant ductus

arteriosus?– Size of the shunt, effect on myocardial performance and end-organ

perfusion

• Evaluation of pulmonary hemodynamics– Degree of pulmonary hypertension vs. impact on myocardial

performance– Presence or absence of shunt

• Troubleshooting systemic hypoperfusion or hypotension– Systolic vs. diastolic performance (afterload effect?)– Low SVC flow, low cardiac output

• Miscellaneous– Confirmation of line placement (assist insertion)– Presence or effusions or thrombi

Defining the Nature of the Problem

Preload MyocardialFunction

Afterload Heart Problem

Rhythm problem

Hypovolaemia Prematurity < 48 hours of life HSDA SVT

Overinflation Sepsis / NEC PDA Ligation Coarctation Complete heart block

Adrenal suppression

Adrenal suppression

Pulmonary hypertension

HLHS

IDM Aortic stenosis

Is the neonatologist reliable?

Does TnECHO improve outcomes?

Challenges• Validity of some measurements• Collaboration with Pediatric Cardiologists

– Income streams– Misdiagnosis & Maltreatment– Terms/Level of Engagement

• Standards for training• Access to equipment (Ownership)• Data storage

Ward 2001 J Pediatr Child HealthDiagnostic Errors 47/110 (44%)

Samson 2004 Card Young

Neonatologist & CHD

626, 781 live births

4295 cases of CHD

451 major cardiac defects

238 (52.8%) cases detected antenatally

Drawing Parallels: Antenatal Diagnosis of CHD

Chew 2007 Ultrasound Obs Gyn

Target group Duration Assessment AccuracyFocused Assessment with Sonography for Trauma

15 scans:

50 scans:

Trauma assessment

sensitivity 90%, accuracy 99% sensitivity 96%, accuracy 100%

McCarter 2000Ann Surg

Limited Echo Assessment Project (LEAP): Residents

20 hours LV function & pericardial effusion

High Alexander 2001 Circulation

Medical students

20 hours LV function & pericardial effusion

Complete echo: 97%Accuracy: 80%

Alexander 2001 Circulation

Non-cardiologist 10 hours LV assessment

Accuracy 87% Manasia 2004 J CardiovascAnesth

Non-cardiologist 4 hours LV function Sensitivity 77%Specificity 94%

Melamed 2004 Chest

Residents 20 hours Complete assessment

Accuracy 93% Croft 2006 Echo

EVIDENCE FROM ADULT TRAINING

PDA Detection

Lee 2007 J PerinatEcho course, DVD & 3 hours with pediatric cardiologist

“Our study shows that it is possible to predict ductal patency without extensive echocardiography training. It also shows us that a neonatology based screening programme for pre-symptomatic arterial ducts in very low birth weight infants would be feasible. “

Walsh 2006 Ir Med J

Didactic: 2 hours lectures Observation: 8 studies Practice: 3 studies

Is the neonatologist reliable?

Does TnECHO improve outcomes?

Efficacy of GDFI in adult care

• Changes in clinical care in 53% of patient Gorcsan 2001 JAMSE

• ↑ diagnostic accuracy (50%) in RCT of goal directed echo for hypotensive patients in ER

Jones 2005 Crit Care Med

Manasia 2004 J Cardiovasc Anesth

Focused Echocardiography in Resuscitation Setting

Breitkrutz 2005 Crit Care Med

PDA Echocardiography research

Time period

1970-79 1980-89 1990-99 2000-present

Num

ber o

f pub

licat

ions

0

5

10

15

20

25

30

Neonatology Cardiology

Intraventricular Hemorrhage

Era

Before After%

0

10

20

30

40

50

60

IVH Gd III/IV

Era I Era II

Gestation [weeks]

26.1[24.5-29.5] 26.6 [23.8-28.1]

PDA diagnosis [days]

4 [2-13] 3 [3-4] *

PDA treatment I [days]

5 [3-25] 3 [3-7] *

PDA treatment II [days]

12 [9-14] 8 [7-9] *

Ventilation [days]

13 [0-66] 9 [1-66] *

Early Detection & Outcome

O’Rouke 2008 Acta Paed

Duration of Indomethacin Treatment of the Preterm PDA as Directed by Echocardiography

Carmo J Pediatr 2009

Premature infants with HSDA

fECHO guided intervention Conventional group

Duration of Indomethacin Treatment of the Preterm PDA as Directed by Echocardiography

• Reduction in indomethacin administration from a median of 3 doses (1-12) to 1 dose (1-15) using fECHO directed therapy

• No increased in need for subsequent indomethacin or PDA ligation

Carmo J Pediatr 2009

Toronto Crisis

• Waiting time for PDA ligation 2-3 weeks

• Delayed time of intervention

• Inconsistent referral pattern

• Post-ligation Cardiac Syndrome (PLCS) common

Enhancing PDA Care• Creation of PDA ligation team

• Comprehensive TnECHO before intervention

• Categorisation system for PDA

• Early postoperative TnECHO to guide neonatal care

PDA Ligation [Toronto]

Year

2004 2005 2006 2007 2008 2009

Rat

e

0

20

40

60

80

100 Triaging system

TnECHO

TnECHO - postop

Dealing with Education and Accreditation

First symposium on First symposium on fECHOfECHO Oct 08 M. Oct 08 M. KluckowKluckow

Recent Initiatives

• Establishment of np-fECHO working group for Canadian Neonatologists (Calgary 2010)

• American Society of Echocardiography Writing group 2010– Guidelines for ECHO in the NICU– Cardiologists, Neonatologists

Use of npFE - Guiding Principles

• Echocardiography information dependant on quality of images and reliability of interpretation (Competence)

• Hemodynamic information should only be used in the context of the clinical scenario (Logic and Reason)

np-fECHO evaluations must be performed by personnel who have completed a

recognised training program, met basic criteria for image acquisition and

interpretation.

Established Standby Interest

Calgary Winnipeg Montreal

Toronto (n=3) Hamilton London

Vancouver Halifax Edmonton

Quebec city

Neonatal Cardiology Specialist

Imaging Equipment

Training Program

Archiving & Reporting

Neonatal Cardiology Consult Model

Clinical Practice Guidelines

Toronto TnECHO Model of Care

CLINICAL RESEARCH EDUCATIONNeonatal cardiovascular consult model of care- Guidelines &Referral process- 3 trained fellows

Prospective observational human studies• PDA Ligation physiology experiments• Milrinone pharmacokinetics• Surfactant hemodynamics• Furosemide and blood transfusion

Translational Sciences• Asphyxial cardiac arrest and vasopressin - piglet• Pulmonary Hypertension collaborations – neonatal rodents

Echocardiography training- Phase I (3 months)- Phase II (3-6 months)Completed by 16 fellowsIn progress – 4 fellows

Neonatal Cardiology Fellowship (TBA) – 1 year

Resources: Publications, WINFOCUS, Evans DVDs

Elective opportunities Elective opportunities- 4 neonatologists (2 4/52)- 1 sabbatical- 6 fellows, next 12 months

Portable laptop systems– HSC / SunybrookRoving machine – 1 siteStandardized image acquisition and protocols

Electronic reporting

Ancillary Resources- Online npfECHO teaching module- Competency evaluation & OSCE development (Finan)

Archiving - ECHOPAC Archiving - ECHOPAC Archiving - ECHOPAC

↓ Ligation rates & PLCSECMO-medical rare

Developmental Hemodynamics group

Global Workshops – PAS, India, Saudi Arabia, AAP

Year

2006 2007 2008 2009 2010

TnEC

HO

0

100

200

300

400

500

Year

2005 2006 2007 2008 2009 2010 2011

Sono

grap

hers

0

1

2

3

4

5

6

7

TnECHO Sonographers

TnECHO training modulePhase I:• Didactic sessions

• Hands-on supervised sessions (12 weeks)– Equipment– Landmarks & standard views– Goal directed assessments

• Ongoing scanning (12 weeks ) : LogbookPhase II:• Independent scanning: Neocardiac rotations /formal

review

• Formal evaluation

Training Modules

1. Physics of Ultrasound 2. 2D, M-mode and Doppler imaging3. Orientation and image acquisition for basic

transthoracic cardiac views 4. Evaluation of left ventricular systolic and

diastolic performance 5. Evaluation of pulmonary hemodynamics6. Evaluation of the ductus arteriosus7. Evaluation of systemic hemodynamics8. Evaluation of indwelling catheters, brain

parenchyma, effusions and bladder.

Maintain logbook - completed a minimum of 50 complete echocardiograms of which 25 are ductusarteriosus evaluations.

Challenges• Learning curve for functional

echocardiography

• Standardized echocardiography approach

• Quality assurance for imaging

• Therapeutic protocol – consistent approach

Scenario III• Term 40 wks gestation; Bwt 5.060 Kg • Severe uncontrolled maternal IDDM• SVD Resp distress intubated & surfactant good

response ventilated on AC on 22/6 in 25% oxygen

• Severe hypoglycemia D20W @ 120ml/kg/day• Insulin level 571• UVC high slightly high on Xray adjusted

• Murmur ECHO; severe septal hypertrophy with mid cavity gradient

• To treat as HOCM if symptomatic

Case Progression• Day 3 extubated in LF• Sugars stable D20W at 120 + glucagon

Day 5 • Glucose 6 at 0600 hrs• Inc to 10 (0900), 14 (1200) 18 (1400)• Lactate 6 8• Poor perfusion, reduced urine output• Increasing resp distress CXR rpt • Inc cardiomegaly + UVC migrated deep in RA• TnECHO performed

Echo clip #1Echo clip #2

• Effusion (TPN) drained under Echo guidance

• Echo next day showed thin rim of effusion and well filled heart

• Extubated to low flow oxygen• Off glucagon over the next 3 days• Transferred to L2 for establishing feeds

Take Home Messages • Targeted Neonatal Echo should be used in combination

with clinical acumen and not as replacement

• The focus is to provide longitudinal hemodynamicinformation in critically ill neonates

• This information either compliments what is clinically suspected or provides novel physiologic insights

• Catalyst for prospective physiology based research

• Issues related to training, accreditation and standards need to be addressed locally and in collaboration with our cardiology colleagues

“Information Age ”Reinvigoration of the physical assessment

“The role of goal directed ultrasound is not to replace or detract from a complete echocardiogramperformed by the pediatric cardiologist but to enhance the physical examination by providing additional real-time physiologic information”

• Point of Care ultrasoundat 20 hrs: Large effusion pleural effusion with severe LV dysfunction

• Chest drain inserted and 40 mls of straw colored fluid [100% lymphocytes]

• Point of Care ultrasoundHypercontractilemyocardium with unrestrictive L-R transductal flow

• PGE1 & pressorsweaned

LV

RV

AO

LA

PDA

PA

Zhang 1999 Arch Dis Child

Dopamine and Afterload

Group 1 Dopamine 8 µg/kg/min

Group 2 Dopamine 6 µg/kg/min

Ultrasound as a research tool Ultrasound as a clinical tool

Clinical Dilemmae.g. hypotension, ductus arteriosus

? Improved Clinical Care

Pillars of Training• Credentialing committees for each country.

• Development and maintenance of standards for both trainees and trainers.

• Ongoing support for trainees (experienced mentor).

• OSCE a useful method for assessment of skills

• Regular re-accreditation of trainees.

• Quality control including a requirement for log books supported by comparison with gold standards.

Sick Neonate

Brain assessment? Hemorrhage MCA Doppler

Abdominal assessment? Ascites Bladder

Renal, mesenteric, celiac Doppler

? Organs present

Heart & lung assessmentPreload Contractility

HSDA CHD

Effusion

Cyanosis (SpO2 65%)? Ebsteins

Brain assessmentVein of Galen malformation

Abdominal assessment

Normal

Heart & lung assessment

PPHN

Dilated SVC with turbulent flow

TnECHO in Canada 2008• fECHO is used less often in

Canada. (79% vs. 91%, p=0.01)

• 86% of respondents reported

that average time to obtain echo

was close to 6hrs

• Most common indications were– Exclude PPHN

– Confirm PPHN

– Assess response to treatment

– Others (serial functional assessment, target therapy, aid weaning)

Comparison of professionals performing FECHO

0

10

20

30

40

50

60

70

80

90

Neonatologist Cardiologist Others

Professional

Prop

ortio

n of

resp

onde

nts

(%)

Canada(n=89)Aus-NZ(n=98)

#

# p<0.05 significant

#

Pre- SRT Assessment

Clinical

2D echo

0 hrs

SRT

30 min 1 hr

A-IIIClinical

2D echo

Post- SRT Assessments

A-IIClinical

2D echo

ABGABG

1 hr

A-III

Clinical2D echoABG

Delivery room echocardiography

Left Ventricle

Ao

PDA Ao SVR+++++

PVR+++

+++

Surfactant

Hyperoxia

Hypocapnia / Alkalosis

Placenta elimination

Hyperoxia

Hypothermia

0 mins 30 mins 60 mins p

LVEDD [mm] 7.1 (6.9, 7.4) 7.4 (7.2, 8.4) 7.5 (7.4, 8.3) * 0.03

Fractional shortening [%] 27.4 ± 9.6 37.9 ± 8.2 * 36.4 ± 7.8 * 0.008

LA : Ao ratio 1.3 ± 0.1 1.37 ± 0.1 * 1.44 ± 0.09 * <0.001

LV output [mls/kg/min] 105.3 ± 37.1 80.6 ± 35.6 65.8 ± 29.9 * 0.04

RV output [mls/kg/min] 37.7 ± 16.6 55.9 ± 10.4 * 69.1 ± 12.2 * < 0.001

Systemic vascular res. [Woods units] 26.2 (22.3, 37.6) 36.2 (28.1, 59.1) 38.3 (35.8, 62.6) 0.09

Surfactant administration is followed by………

• Increased systolic but decreased diastolic BP.

• Increased ductal size and exclusive left-to-right transductal flow within the first hour of life.

• Extremely low pulmonary and systemic blood flow in first hour of life

• Redistribution of the amount of pulmonary and systemic blood flow resulting in increased Qp:Qs

RVO LVOSVRPVR

…………

…………

Japanese Experience• TnECHO

– Delivery room and 8 hourly until 96 hours

– Day 7 & 10– Weekly evaluation x 6

weeks, & discharge– Strict Protocols with

management approach

Merits Challenges

All doctors trained

24/7 coverage

Dedicated up-to-date equipment

Standardized image acquisition and protocols

Brief study (10-15 mins)

Electronic reporting and archiving system

Lack of scientific validation for many hemodynamicmarkers (e.g. IVC diameter, ESWS)

Ad-hoc Echocardiography training