poznan role of npe wpdeboode [191130] - noworodek.edu.pl · 1department of neonatology, radboud...

02-12-2019

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W.P. de [email protected]

Role of Neonatologist PerformedEchocardiography (NPE) in Neonatal Care

Willem P. de Boode, MD PhDRadboudumc Amalia Children’s Hospital

Nijmegen, The Netherlands

[email protected]

SYMPOSIUM PROGRAMME Friday 29th 8.50 – 09.00 Welcome - Marta Szymankiewicz Session 1 Quality Care Improvement in the NICU 9.00 – 9.20 Why we need European Standards of Care for Newborn Health Zimmermann (Maastricht, The Netherlands9.20 – 9.40 Why we need European Standards of Care for Newborn Health Mader (EFCNI, Germany) 9.40 – 10.00 The role of family centered developmental care10.00 – 10.10 Psychologist approach to10.10 – 10.30 Challenging routine nursing practice improvement - Izabela Andrzejewska (10.30 – 10.50 Neonatal epidemiology Poland) 10.50 – 11.05 Discussion Session 2 Cerebral ultrasound – session (EurUSbrain) group 11.05 – 11.35 Clinically relevant neonatal brain doppler imagingBelgium) 11.35 – 11.55 The neonatal early admission sonogram11.55 – 12.15 Preterm white matter injury: ultrasou(EurUSbrain-group, Berlin, Germany12.15 – 12.35 Ultrasound of acquired posterior fos(EurUSbrain-group, Leiden, The Netherlands12.35 – 12.55 Cranial ultrasound findings in preterm germinal matrix hemorrhage, sequelae and outcome Luca Ramenghi (EurUSbrain-group, Bergamo, Italy12.55 – 13.10 Discussion 13.10 – 14.10 Lunch Session 3 Respiratory problems 14.10 – 14.30 Cooperation between WO!P

Endorsement:

SYMPOSIUM PROGRAMME

Marta Szymankiewicz-Br"borowicz, Tomasz Szczapa

Quality Care Improvement in the NICU – session organized in cooperation with EFCNI

need European Standards of Care for Newborn Health – the medical perspectiveThe Netherlands)

we need European Standards of Care for Newborn Health – the parent perspective

ily centered developmental care - Liisa Lehtonen (Turku, Finland)pproach to family centered care - Anna Stola# (Pozna$, Poland

Challenging routine nursing practice - neonatal research nurse perspectIzabela Andrzejewska (Londyn, UK) Neonatal epidemiology – selected issues – Abbvie educational grant - Ewa Helwich (

session organized in cooperation with European Brain Ultrasound

Clinically relevant neonatal brain doppler imaging - Paul Govaert (EurUSbrain

onatal early admission sonogram - Eva Valverde (EurUSbrain-groupPreterm white matter injury: ultrasound diagnosis and classification –

Germany) Ultrasound of acquired posterior fossa abnormalities in the newborn - Steggerda Sylke

The Netherlands) Cranial ultrasound findings in preterm germinal matrix hemorrhage, sequelae and outcome

group, Bergamo, Italy)

ration between WO!P and polish neonatologists – Jurek Owsiak (WO!P

nized in cooperation with EFCNI

the medical perspective - Luc

parent perspective - Silke

, Finland) , Poland)

perspective of quality care

Ewa Helwich (Warsaw,

n Ultrasound

Paul Govaert (EurUSbrain-group, Gent,

group, Madrid, Spain) Sandra Horsch

Steggerda Sylke

Cranial ultrasound findings in preterm germinal matrix hemorrhage, sequelae and outcome –

Jurek Owsiak (WO!P Charity Fund)

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Role of NPE in Neonatal CareIntroduction• Use of echocardiography for the evaluation of the

cardiovascular well-being of term and preterm infants is gaining significant interest.

’Bedside use of echocardiography to longitudinally assess myocardial function, systemic and pulmonary blood flow,

intracardiac and extra cardiac shunts, organ flow and tissue perfusion in critically ill newborn infants’

Kluckow M, Seri I, Evans N. Functional echocardiography: An emerging clinical tool for the neonatologist. J Pediatr 2007, Feb;150(2):125-30

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Role of NPE in Neonatal CareTerminology

• Functional Echocardiography (fECHO)• Point-of-Care Echocardiography (POC-Echo)• Targeted Neonatal Echocardiography (TNE)• Clinician Performed Ultrasound (CPU)• Point-Of-Care UltraSound (POCUS)• Neonatologist Performed Echocardiography (NPE)

Poon WB, Wong KY. Neonatologist-performed point-of-care functional echocardiography in the neonatal intensive care unit. Singapore Med J. 2017;58(5):230-3.

NPPOCfEcho

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NPE Collaborative (ESPR/EBN)

Identifies the person performing the assessment and the target organ assessed.

Role of NPE in Neonatal CareTerminology

Neonatologist Performed Echocardiography

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Role of NPE in Neonatal CareIntroduction

Goals• to enhance clinical assessment, diagnosis and

management• to monitor the response to therapeutic

interventions• to gain insight in (patho)physiologic

haemodynamic processes

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Survey 40 NICUs in 17 European countries (2013)• Neonatologists with skills in fECHO in 74% of NICUs• Dedicated ultrasound machines available

on 89% NICUs• fECHO performed by:

• pediatric cardiologists (55%)• neonatologists (37%)• adult cardiologists (5%)• dedicated echo technician (3%)

• 88% (n=35) - 7-day a week ECHO service• 78% (n=31) - 24h ECHO service on weekdays

1. Roehr CC, Te Pas AB, Dold SK, et al. Investigating the European perspective of neonatal point-of-care echocardiography in the neonatal intensive care unit-a pilot study. Eur J Pediatr 2013;172:907-11

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Survey 40 NICUs in Europe• 22 NICUs (55%) offered teaching to trainees

• mainly by paediatric cardiologists (55%)• by neonatologists (45%)

• Only 6 (15 %) national colleges accredited NPE teaching courses

1. Roehr CC, Te Pas AB, Dold SK, et al. Investigating the European perspective of neonatal point-of-care echocardiography in the neonatal intensive care unit-a pilot study. Eur J Pediatr 2013;172:907-11

Lack of formal training and accreditationof NPE skills

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Need to ensure standardization of training and clinical practice guidelines, with quality assurance systems in place to

maintain safe dissemination of this practice

Available guidelines?

Role of NPE in Neonatal CareGuidelines

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9

http://radboudumc.nl

02-12-2019

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Neonatologist Performed EchocardiographyWhy new guidelines?

Existing guidelines are rather difficult to implement in a pan European setting, given the heterogeneous

nature of training facilities, personnel and infrastructure

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•2 day course•25-50 US examinations

MinimalisticTraining Approach(Australia & New

Zealand)•150 performed scans•150 reviewed scans• 4-6 months dedicated

paediatric echocardio-graphy laboratory

MaximalistTraining Approach(North America &

Europe)

Structural Heart Defect?establish gross structural normality or

confidently exclude structural heart defect


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Pragmatism Safety

Promote NPE as a clinical tool

Role of NPE in Neonatal CareEuropean Guideline NPE Collaborative

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de Boode WP et al. Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research (ESPR) and European

Society for Neonatology (ESN). Pediatr Res 2016;80:465-71.

Official journal of the International Pediatric Research Foundation, Inc.

Special Articlenature publishing group

INTRODUCTION!e use of echocardiography for the evaluation of the cardio-vascular well-being of term and preterm infants is gaining sig-ni"cant interest. !e aim of echocardiography in this setting is to provide hemodynamic information in real time in order to support bedside clinical decision making (1–3). !is approach is perceived to enhance clinical judgment, provide a better understanding of active physiological processes, and monitor the response to treatment. Combination of clinical examina-tion and bedside echocardiography has been shown to facili-tate clinical decision making (4). !ere is some evidence that routine use of echocardiography on the neonatal unit might lead to early identi"cation of cardiovascular compromise that could facilitate clinical management (5), potentially improving short-term outcomes (6,7). !ere is growing literature high-lighting the potential merits of echocardiography in the iden-ti"cation of cardiovascular compromise and guiding neonatal cardiovascular care (4,6,8,9).

!ere is a need to ensure standardization of training and clinical practice guidelines, with quality assurance systems in place to maintain safe dissemination of this practice. !ere are currently two published guidelines in neonatal echocardiog-raphy with recommendations for training and an accredited structured training program with accreditation in neonatal cardiac ultrasound. !e practice guidelines and recommen-dations for the use of echocardiography (Targeted Neonatal Echocardiography (TNE)) and Expert consensus statement on Neonatologist performed echocardiography (NoPE) in the United Kingdom were published in the last 5 y (10,11).

However, some aspects of these two guidelines are di#cult to implement in a pan European setting. !e Australian Society of Ultrasound in Medicine has developed and implemented a basic training and accreditation process in Australia encom-passing cardiac, brain, and abdominal ultrasound that is dif-"cult to adopt in Europe (http://www.asum.com.au).

As a result, a working group under the auspices of the European Society for Paediatric Research and the European Society for Neonatology was convened to devise a consensus statement for neonatologist performed echocardiography training taking into account the heterogeneous nature of training facilities, personnel, and infrastructure across Europe. In this statement, we aim to (i) highlight the di#culties in implementing the cur-rent TNE and UK guidelines in a European setting; (ii) de"ne the training facilities and infrastructure necessary for optimal training conditions; (iii) identify training standards applicable across Europe; and (iv) discuss some practical aspects including a suggested governance structure for oversight of training and continued quality assurance. We have elected to use the term neonatologist performed echocardiography (NPE) as used in the UK guideline because it identi"es the person performing the assessment and the target organ assessed.

!is consensus statement deals with NPE for assessment of hemodynamic function in infants with a structurally normal heart (patent ductus arteriosus (PDA) and patent foramen ovale included). Although con"rmation of normal structural anatomy is within the remit of this practice, diagnosis and management of congenital heart disease (CHD) is beyond the scope of this guideline. !is practice should always remain

Received 16 February 2016; accepted 8 April 2016; advance online publication 6 July 2016. doi:10.1038/pr.2016.126

1Department of Neonatology, Radboud University Medical Center, Nijmegen, The Netherlands; 2Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; 3University Hospital of North Tees, Durham University, Stockton-on-Tees, UK; 4Department of Neonatology, Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; 5Department of Neonatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; 6INFANT Centre, Cork University Maternity Hospital, University College Cork, Cork, Ireland; 7Weill Cornell Medical College New York, New York, New York; 8Department of Pediatrics, Møre and Romsdal Hospital Trust, Ålesund, Norway; 9Department of Pediatrics, Antwerp University Hospital UZA, Edegem, Belgium; 10Department of Physiology, Anatomy and Genetics, John Radcliffe Hospital, Oxford, UK; 11Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 12Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 13Department of Neonatology, The Royal Women’s Hospital, Parkville, Victoria, Australia; 14Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; 15 Pediatric Cardiology Unit, Geneva University Children’s Hospital, Geneva, Switzerland; 16Department of Neonatology, Emma Childrens’ Hospital AMC, Amsterdam, The Netherlands; 17Department of Neonatology, University Hospital Brussels, Brussels, Belgium; 18Department of Neonatology, The Rotunda Hospital, Dublin, Ireland; 19School of Medicine (Department of Pediatrics), The Royal College of Surgeons in Ireland, Dublin, Ireland. Correspondence: Willem P. de Boode ([email protected])

Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research (ESPR) and European Society for Neonatology (ESN)Willem!P.!de!Boode1, Yogen!Singh2, Samir!Gupta3, Topun!Austin4, Kajsa!Bohlin5, Eugene!Dempsey6, Alan!Groves7, Beate!Horsberg!Eriksen8, David!van!Laere9, Zoltan!Molnar10, Eirik!Nestaas11,12, Sheryle!Rogerson13, Ulf!Schubert14, Cécile!Tissot15, Robin!van!der!Lee16, Bart!van!Overmeire17 and A"f!El-Khu#ash18,19

Pediatr Res

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00

2014

Pediatric Research

10.1038/pr.2016.126

6July2016

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16February2016

8April2016

O#cial journal of the International Pediatric Research Foundation, Inc.

NPE training guidelines in Europe

de Boode et al.

Special Article

Open

Pediatric RESEARCH 1

Role of NPE in Neonatal CareEuropean Guideline NPE Collaborative (ESPR)

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E/D Cardiologist• cross-sectional• focus on structure

(& function)• consultative• advise and

backup

E/D Neonatologist• longitudinally• focus on function

(& structure)• monitoring effect

of management• 24/7

Role of NPE in Neonatal CareCardiologist versus Neonatologist

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Role of NPE in Neonatal CareCongenital Heart Disease

Any patient with suspected or confirmed structural heart

disease should be referred to a paediatric cardiologist!

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• Patent ductus arteriosus• Persistent pulmonary hypertension of the newborn• Neonatal shock / hypotension• Feto-neonatal transition• Hypoxic-ischaemic encephalopathy• Congenital diaphragmatic hernia• Intravascular line placement• Identification of pericardial effusion

Role of NPE in Neonatal CareIndications for NPE

Groves A. et al. Introduction to Neonatologist Performed Echocardiography. Pediatr Res. 2018;84(S1):1-12.

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Neonatologist Performed EchocardiographyConsiderations for scanning preterm infants• Ask the nurse for assistance (comfort, monitoring)• Clear electrocardiogram signal• Take time to ensure optimal environment for imaging• Use of warm sterile ultrasound gel, preferably single use gel

sachets• Use of minimal pressure on the skin• Be especially sensitive in the subcostal views• Duration of first scan limited to 30 minutes• Subsequent scans not more than 15 minutes duration• Offline measurement of dimensions and function

Groves A. et al. Introduction to Neonatologist Performed Echocardiography. Pediatr Res. 2018;84(S1):1-12.

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• ‘With due care it is possible to perform echocardiography in the preterm infant to gain valuable haemodynamic information without significantly disturbing cardiorespiratory status’

• Cerebral haemodynamics and systemic and cerebral oxygenation are not perturbed during TnEcho and the procedure is well tolerated by the extremely preterm infants during the postnatal transitional period

• No evidence of an association between serial TnEcho studies and the development of P/IVH

• Facilitated tucking during NPE improves infant’s comfort and is associated with lower pulmonary pressures

Neonatologist Performed EchocardiographyPatient safety during echocardiography

Groves AM, Kuschel CA, Knight DB, Skinner JR. Cardiorespiratory stability duringechocardiography in preterm infants. Arch Dis Child. 2005;90(1):86-7.

Noori S, Seri I. Does targeted neonatal echocardiography affect hemodynamics and cerebral oxygenation in extremely preterm infants? J Perinatol 2014, Nov;34(11):847-9.

Gautheyrou L, Durand S, Jourdes E, De Jonckheere J, Combes C, Cambonie G. Facilitated tucking during earlyneonatologist-performed echocardiography in very preterm neonates. Acta Paediatr. 2018;107(12):2079-85.

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• Patent ductus arteriosus• Prediction of hemodynamic significance and

adverse outcomes• Reduction of intensity of treatment• Prevention of complications after ductal ligation

Role of NPE in Neonatal CareBenefits? Impact on PDA management

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Echocardiographic indices of shunt volume dimension SMALL MODERATE LARGE

Characteristics of the PDA

Absolute diameter mm <1.5 1.5 - 2.0 ≥2.0

PDA:LPA diameter-ratio - <0.5 0.5 - 1.0 ≥1.0

PDA diameter indexed to body weight mm/kg - - ≥1.4

Transductal peak systolic velocity m/s >2.0 1.5 - 2.0 <1.5

Transductal systolic to diastolic velocity gradient - <2.0 2.0 - 4.0 >4.0

Pulmonary hyperperfusion

End-diastolic blood flow velocity in LPA cm/s <20 20 - 50 >50

Pulmonary vein diastolic (D-) wave velocity cm/s <0.3 0.3 - 0.5 >0.5

LA/Ao-ratio - <1.5 1.5 - 2.0 >2.0

LVEDD Z-score

LVO mL/kg/min <200 200-300 >300

Mitral valve E/A-ratio - <1 1 >1

LV-IVRT ms >40 30-40 <30

Systemic hypoperfusion

Diastolic blood flow pattern in systemic arteries (DAo, MCA, PCA, CT, SMA, RA) - Antegrade Absent Retrograde

Qp/Qs-ratio

LVO/SVCf-ratio - - - ≥4.0

Ao, aortic root; DAo, descending aorta; LA, left atrium; LPA, left pulmonary artery; LV-IVRT, left ventricular isovolumic relaxation time; LVEDD, left ventricular end-diastolic dimension; LVO, left ventricular output; PDA, patent ductus arteriosus; Qp, pulmonary blood flow; Qs, systemic blood flow; SVCf, superior vena cava flow;

�1

Role of NPE in Neonatal CareEchocardiographic indices of PDA shunt volume

de Boode WP, Kluckow M, McNamara PJ, Gupta S. Role of neonatologist-performed echocardiography in the assessment and management of patent ductus arteriosus

physiology in the newborn. Semin Fetal Neonatal Med. 2018;23(4):292-7..

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Role of NPE on Neonatal CareEchocardiographic indices of PDA shunt volumeEchocardiographic indices Cut-off value PNA at

assessment Prediction LR+ LR- Reference

Absolute ductal diameter ≥1.5 mm <31 hrs hsPDA (clinical & echocardiographic) @ PNA 1-15 days 5,4 0,22 Kluckow, 1995

≥1.5 mm 3 days Failure of closure without treatment @ PNA 10 days 3,4 0,32 Thankavel, 2013

>2.1 mm <48 hrs PDA ≥2 mm @ PNA 1 month 6,5 0,25 Smith, 2015

≥2.0 mm 7 days Need for future PDA treatment (> PNA 7 days) 947 0,05 Yum, 2017

PDA diameter indexed to body weight

>1.5 mm/kg 12-48 hrs hsPDA with indication for ligation 3,5 0,08 Kwinta, 2009

>2.0 mm/kg 24 hrs Need for subsequent treatment (clinical & echocardiographic) 2,2 0,15 Harling, 2011


PDA:LPA diameter-ratio ≥ 0.5 <4 days Need for subsequent treatment (clinical & echocardiographic) 3,9 0,28 Ramos, 2010

≥ 0.5 3 days Failure of closure without treatment @ PNA 10 days 2,0 0,15 Thankavel, 2013

Transductal systolic to diastolic velocity gradient

>1.9 <48 hrs PDA ≥2 mm @ PNA 1 month 8,8 0,13 Smith, 2015

≥2.0 7 days Need for future PDA treatment (> PNA 7 days) 5,4 0,13 Yum, 2017

Transductal blood flow pattern

Initial “Growing” <7 days hsPDA (clinical, radiological & echocardiographic) @ PNA <7 days 3,4 0,44 Su, 1997

Initial “Pulsatile” <7 days hsPDA (clinical, radiological & echocardiographic) @ PNA <7 days ∞ 0,07 Su, 1997

“Pulsatile” 24 hrs Need for subsequent treatment (clinical & echocardiographic) 2,2 0,15 Harling, 2011


LA/Ao-ratio ≥1.4 24 hrs Need for subsequent treatment (clinical & echocardiographic) 1,0 1,03 Harling, 2011

≥1.4 72 hrs Need for subsequent treatment (clinical & echocardiographic) 1,1 0,88 Harling, 2011

≥1.4 3 days Failure of closure without treatment @ PNA 10 days 3,2 0,15 Thankavel, 2013

≥1.5 <31 hrs hsPDA (clinical & echocardiographic) @ PNA 1-15 days 3,2 0,78 Kluckow, 1995


Left ventricular output ≥300 mL/kg/min <31 hrs hsPDA (clinical & echocardiographic) @ PNA 1-15 days 3,3 0,80 Kluckow, 1995

Mitral valve E/A-ratio >1 3 days Failure of closure without treatment @ PNA 10 days 1,1 0,00 Thankavel, 2013

LR+ LR- Test classification

>10-20 <0.05-0.10 Good test

2-10 0.10-0.50 Intermediate test

<2-4 >0.25-0.50 Poor test

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Echocardiographic indices Cut-off value PNA at assessment Prediction LR+ LR- Reference

Absolute ductal diameter ≥1.5 mm <31 hrs hsPDA (clinical & echocardiographic) @ PNA 1-15 days 5,4 0,22 Kluckow, 1995

≥1.5 mm 3 days Failure of closure without treatment @ PNA 10 days 3,4 0,32 Thankavel, 2013

>2.1 mm <48 hrs PDA ≥2 mm @ PNA 1 month 6,5 0,25 Smith, 2015

≥2.0 mm 7 days Need for future PDA treatment (> PNA 7 days) 947 0,05 Yum, 2017

PDA diameter indexed to body weight

>1.5 mm/kg 12-48 hrs hsPDA with indication for ligation 3,5 0,08 Kwinta, 2009



PDA:LPA diameter-ratio ≥ 0.5 <4 days Need for subsequent treatment (clinical & echocardiographic) 3,9 0,28 Ramos, 2010

≥ 0.5 3 days Failure of closure without treatment @ PNA 10 days 2,0 0,15 Thankavel, 2013

Transductal systolic to diastolic velocity gradient

>1.9 <48 hrs PDA ≥2 mm @ PNA 1 month 8,8 0,13 Smith, 2015


Transductal blood flow pattern

Initial “Growing” <7 days hsPDA (clinical, radiological & echocardiographic) @ PNA <7 days 3,4 0,44 Su, 1997

Initial “Pulsatile” <7 days hsPDA (clinical, radiological & echocardiographic) @ PNA <7 days ∞ 0,07 Su, 1997



LA/Ao-ratio ≥1.4 24 hrs Need for subsequent treatment (clinical & echocardiographic) 1,0 1,03 Harling, 2011

≥1.4 72 hrs Need for subsequent treatment (clinical & echocardiographic) 1,1 0,88 Harling, 2011

≥1.4 3 days Failure of closure without treatment @ PNA 10 days 3,2 0,15 Thankavel, 2013

≥1.5 <31 hrs hsPDA (clinical & echocardiographic) @ PNA 1-15 days 3,2 0,78 Kluckow, 1995


Left ventricular output ≥300 mL/kg/min <31 hrs hsPDA (clinical & echocardiographic) @ PNA 1-15 days 3,3 0,80 Kluckow, 1995

Mitral valve E/A-ratio >1 3 days Failure of closure without treatment @ PNA 10 days 1,1 0,00 Thankavel, 2013

LR+ LR- Test classification

>10-20 <0.05-0.10 Good test

2-10 0.10-0.50 Intermediate test

<2-4 >0.25-0.50 Poor test

�1

de Boode WP, Kluckow M, McNamara PJ, Gupta S. Role of neonatologist-performed echocardiography in the assessment and management of patent ductus arteriosus

physiology in the newborn. Semin Fetal Neonatal Med. 2018;23(4):292-7..

21


• Multicenter prospective observational study• 141 preterm infants (GA<29 weeks; mean 26±1.4)• PDAsc using markers of pulmonary hyperperfusion and

LV diastolic function• Predictive value for CLD/Death

• PPV 92%• NPV 82%

and NEC. Infants with CLD had a significantly higher score(7.2 [1.9] vs 3.8 [2.0], P < .001). Similarly, infants that diedbefore discharge has a higher score (7.7 [1.7] vs 5.7 [2.5],P = .01). Finally, infants with NEC had a higher PDAscthan those without NEC (7.5 [2.3] vs 5.6 [2.4], P < .003).The PDAsc had an AUC of 0.70 (95% 0.57-0.81, P = .007)for the ability to predict NEC.

Discussion

We demonstrate that there are early differences in character-istics of the PDA during the first week of life between infants

who develop CLD or die before discharge and those who donot develop those outcomes, with increasing divergence ofthose characteristics over the first week of life. The pheno-typic features of these higher risk patients include largerPDA diameter, lower maximum velocity across the PDA(indicating a lack of ductal constriction and an unrestrictedflow pattern in the absence of significant pulmonary hyper-tension), and increased pulmonary blood flow (indicatedby a higher LVO). In addition, a PDAsc derived on day 2of age using gestation along with echocardiography markersof PDA characteristics and LV diastolic function can predictthe later occurrence of CLD or death in a group of preterminfants less than 29 weeks gestation.There has been a recent reemphasis to develop a better defi-

nition of PDA “hemodynamic significance,” which resultedfrom the failure of all randomized controlled trials ofpre-symptomatic PDA treatment to yield an improvementin short- and long-term PDA associated morbidities.2,17 Allof these studies, however, treated the PDA as an all-or-nonephenomenon, with no quantification of the impact the PDAhas on pulmonary or systemic blood flow. Those trials reliedalmost solely on PDA diameter to determine significance. Thisover-simplification ignores the effect of shunt volume indetermining PDA significance. The PDA in the prematureinfant’s early life should be regarded as a continuum frombeing physiologic, and potentially beneficial to being patho-logic (when pulmonary vascular resistance drops) leading tosystemic hypoperfusion and pulmonary congestion. Thereare several challenges with defining hemodynamic significanceassociated with a PDA. A variety of definitions for hemody-namic significance have been employed which incorporateclinical and echocardiography variables without clear valida-tion and justification.11 In addition, the cut-offs at whichechocardiography PDA characteristics are assigned signifi-cance are often allocated based on whether infants receivedtreatment or not rather than associating them withmorbidity,18,19 or are based on the short-term occurrence ofclinical features of a PDA such as bounding pulses, a murmur,and an active precordium.20

Figure 3. Receiver operating characteristics curve of theability of PDAsc to predict CLD/death. The PDAsc wascompared with a combination of clinical characteristics,gestation, and PDA diameter.

Figure 2. Difference in theA, PDAsc between infants with and without CLD/death and theB, relationship between the score andthe predicted probability of CLD/death in the entire cohort. Infants who developed CLD/death had a higher predicted probabilitycompared with those who did not.

THE JOURNAL OF PEDIATRICS ! www.jpeds.com Vol. 167, No. 6

1358 EL-Khuffash et al

Role of NPE in Neonatal CarePDA Severity Score (PDAsc)

El-Khuffash A, James AT, Corcoran JD, Dicker P, Franklin O, Elsayed YN, et al. A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge.

J Pediatr. 2015;167(6):1354-61 e2.

7.3±1.8

3.8±2.0

and NEC. Infants with CLD had a significantly higher score(7.2 [1.9] vs 3.8 [2.0], P < .001). Similarly, infants that diedbefore discharge has a higher score (7.7 [1.7] vs 5.7 [2.5],P = .01). Finally, infants with NEC had a higher PDAscthan those without NEC (7.5 [2.3] vs 5.6 [2.4], P < .003).The PDAsc had an AUC of 0.70 (95% 0.57-0.81, P = .007)for the ability to predict NEC.

Discussion

We demonstrate that there are early differences in character-istics of the PDA during the first week of life between infants

who develop CLD or die before discharge and those who donot develop those outcomes, with increasing divergence ofthose characteristics over the first week of life. The pheno-typic features of these higher risk patients include largerPDA diameter, lower maximum velocity across the PDA(indicating a lack of ductal constriction and an unrestrictedflow pattern in the absence of significant pulmonary hyper-tension), and increased pulmonary blood flow (indicatedby a higher LVO). In addition, a PDAsc derived on day 2of age using gestation along with echocardiography markersof PDA characteristics and LV diastolic function can predictthe later occurrence of CLD or death in a group of preterminfants less than 29 weeks gestation.There has been a recent reemphasis to develop a better defi-

nition of PDA “hemodynamic significance,” which resultedfrom the failure of all randomized controlled trials ofpre-symptomatic PDA treatment to yield an improvementin short- and long-term PDA associated morbidities.2,17 Allof these studies, however, treated the PDA as an all-or-nonephenomenon, with no quantification of the impact the PDAhas on pulmonary or systemic blood flow. Those trials reliedalmost solely on PDA diameter to determine significance. Thisover-simplification ignores the effect of shunt volume indetermining PDA significance. The PDA in the prematureinfant’s early life should be regarded as a continuum frombeing physiologic, and potentially beneficial to being patho-logic (when pulmonary vascular resistance drops) leading tosystemic hypoperfusion and pulmonary congestion. Thereare several challenges with defining hemodynamic significanceassociated with a PDA. A variety of definitions for hemody-namic significance have been employed which incorporateclinical and echocardiography variables without clear valida-tion and justification.11 In addition, the cut-offs at whichechocardiography PDA characteristics are assigned signifi-cance are often allocated based on whether infants receivedtreatment or not rather than associating them withmorbidity,18,19 or are based on the short-term occurrence ofclinical features of a PDA such as bounding pulses, a murmur,and an active precordium.20

Figure 3. Receiver operating characteristics curve of theability of PDAsc to predict CLD/death. The PDAsc wascompared with a combination of clinical characteristics,gestation, and PDA diameter.

Figure 2. Difference in theA, PDAsc between infants with and without CLD/death and theB, relationship between the score andthe predicted probability of CLD/death in the entire cohort. Infants who developed CLD/death had a higher predicted probabilitycompared with those who did not.


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NPE guided PDA management• Reduction in number of doses of COXi• Fewer adverse effects• No difference in ductal closure rate• No obvious effects on closure failure, ductal reopening,

surgical ligation, or clinical outcomes, such as pulmonary haemorrhage, BPD, NEC, or renal failure

Patent Ductus ArteriosusReduction of intensity of PDA treatment

Su BH, Peng CT, Tsai CH. Echocardiographic flow pattern of patent ductus arteriosus: a guide toindomethacin treatment in premature infants. Arch Dis Child Fetal Neonatal Ed. 1999;81(3):F197-200.

Carmo KB, Evans N, Paradisis M. Duration of indomethacin treatment of the preterm patent ductus arteriosus as directed by echocardiography. J Pediatr. 2009;155(6):819-22.e1.

Bravo MC et al. Randomised controlled clinical trial of standard versus echocardiographically guided ibuprofen treatment for patent ductus arteriosus in preterm infants: a pilot study. J Matern Fetal Neonatal Med. 2014;27(9):904-9.

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• Postligation cardiac syndrome (PLCS): oxygenation failure, ventilatory failure & systemic hypotension

• Retrospective analysis to detect sensitive predictors of postoperative cardiorespiratory instability (62 preterm infants)

• LVO<200 mL/kg/min at 1 hour after PDA ligation was a sensitive predictor of systemic hypotension and the need for inotropes

Jain A, Sahni M, El-Khuffash A, et al. J Pediatr 2012;160:584-589.e1

TnECHO data were excluded. The included infants hadamean gestational age of 25.5! 2.0 weeks and amedian birthweight of 730 g (650-850 g) and had complete preoperativeand 1- and 8-hour postoperative TnECHO data availablefor review. The median age and weight at the time of surgerywere 26.5 days (20-35 days) and 945 g (880-1200 g), respec-tively. PDA ligation was associated with reductions in LVO(P < .001), fractional shortening (P < .001), and left ventric-ular end-diastolic diameter (P < .001) and prolongation ofisovolumetric relaxation time (P < .001) at both 1 hour and8 hours postligation compared with respective preoperativevalues. LVO at 1 hour and LVO at 8 hours had a high degreeof linear correlation (r = 0.63; P < .001; Figure 1; available atwww.jpeds.com) and was associated with low systolic arterialpressure and need for inotropic agents (P < .05). None of theother echocardiographic markers tested showed a significantcorrelation with any of the desired outcomes. Interestingly,all excluded infants had a 1-hour LVO <200 mL/kg/minand needed inotropic agents postoperatively.

Predictive Value of 1-Hour LVOEighteen infants exhibited critically low LVO (<170 mL/kg/min) at 8 hours, coinciding with the clinical deterioration.Of these infants, 15 already had critically low LVO at 1hour postligation, whereas the other 3 had an LVO of 170-200 mL/kg/min. Six infants with an LVO <200 mL/kg/minat 1 hour did not develop a critically low LVO at 8 hours. Re-ceiver operating characteristic curves were constructed to de-termine the ability for TnECHO at 1 hour postligation topredict subsequent hemodynamic deterioration. LVO at 1hour postligation yielded an area under the curve of 0.94(95% CI, 0.87-1.0; P < .001) for predicting critically lowLVO at 8 hours after surgery, with a cutoff value of 198mL/kg/min, providing a sensitivity of 1.0 and specificity of0.89 (Figure 2, A). It also yielded an area under the curveof 0.90 (95% CI, 0.82-0.98; P < .001) for predicting theneed for inotropic agents with the same cutoff provideda sensitivity of 1.0 and specificity of 0.65 (Figure 2, B).

A threshold of a 1-hour postligation LVO <200 mL/kg/min would have identified all infants with critically lowLVO at 8 hours postligation (positive likelihood ratio, 7.3;95% CI, 3.5-15.4), 83% (10 of 12) of infants who subse-quently developed systolic hypotension (sensitivity, 0.83[95% CI, 0.55-0.95]; specificity, 0.72 [95% CI, 0.58-0.82];positive likelihood ratio, 3 [95% CI, 1.8-5.0]; negative likeli-hood ratio, 0.23 [95% CI, 0.06-0.83]; OR, 12.9 [95% CI,2.5-66.2]), and all infants (n = 9) who required inotropictreatment (positive likelihood ratio, 3.5; 95% CI, 2.3-5.4).

Study BFifty-seven preterm infants underwent PDA ligation in epoch2, all of whom underwent TnECHO evaluation within 1 hourof ligation. Of these, 27 infants had an LVO <200 mL/kg/minand received i.v. milrinone infusion. After matching, 25 in-fants who had an LVO <200 mL/kg/min at 1 hour postliga-tion were selected from epoch 1. There were no differencesin baseline demographic data, comorbidities, preoperativeclinical status, and preoperative and 1-hour postoperativeTnECHO measures between the 2 epochs (Table I). Allinfants treated with inotropic agents had documentedhypotension and received at least 20 mL/kg of fluidresuscitation before initiation of inotropic therapy.Treatment was initiated with either dobutamine ordopamine, at the discretion of the attending staffneonatologist. No other inotropic agent was used. Allneonates treated with steroids had hypotensionunresponsive to simultaneous infusion of both agents(minimum infusion rate, 10 mg/kg/min of each). Neonatesin epoch 2 demonstrated a significant improvement inclinical indices of postoperative cardiorespiratory stability(Table II). Diastolic arterial pressure increased over time inboth epochs, with no intergroup difference. Treatment withprophylactic milrinone infusion was associated with loweroccurrences of both the primary and all secondaryoutcomes (Table III). The absolute risk reduction in PLCSbetween epochs was 0.31 (95% CI, 0.06-0.52), leading to

Figure 2. Receiver operator characteristic curve for LVO at 1 hour after PDA ligation. Sensitivity versus false-positive in pre-dicting A, LVO <170 mL/kg/min at 8 hours postligation and B, the need for inotropes within 24 hours postligation.

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586 Jain et al

Patent Ductus ArteriosusPrevention of PLCS

AUC 0.94Se 1.0

Sp 0.89

AUC 0.90Se 1.0

Sp 0.65

Critically low LVO @ 8h after ligation Need for inotropes

24


• Targeted initiation of intravenous milrinone based on NPE (LVO <200 mL/kg/min @ 1 hr after ligation)

• Comparative evaluation between matched infants in the previous era (epoch 1; n = 25) with a conventional therapeutic approachand the current era (epoch 2; n = 27) of NPE-guided treatment• Lower incidence of ventilation failure (15% vs 48%; P = .02)• Less need for inotropes (19% vs 56%; P = .01)• Trend toward improved oxygenation (P = .08)

Jain A, Sahni M, El-Khuffash A, et al. J Pediatr 2012;160:584-589.e1

Studies in an immature primate model13 and in human pre-term infants11 demonstrated that ligation was followed byimpaired left ventricular systolic function and reduced car-diac output, which coincided with increased systemic vascu-lar resistance. Systolic myocardial function was moresensitive to afterload in neonates compared with older chil-dren.14 This sensitivity likely is even greater in preterm in-fants. The association of PDA ligation with impaired leftventricular performance and low LVO has been welldescribed.5,11,15,16

Study A is a large echocardiography-based analysis of thispopulation, which increases the validity of our findings. Al-though the data were analyzed retrospectively, all measure-ments were collected prospectively. We believe that thedata are representative, given that the overall incidence ofPLCS and its components observed in epoch 1 were similarto those reported previously.4-6 LVOwas the sole marker cor-related with subsequent clinical deterioration. This may beexplained by the fact that LVO is influenced by both preloadand afterload, both of which change very rapidly after PDAligation. We found no correlation between indices of systolicfunction and subsequent PLCS. This may be related to thedifferential responsiveness of the myocardium to alteredloading conditions, with early impairment in systolic perfor-mance in some patients but compensatory increases in con-tractility in others. The correlation between the thresholdvalue of LVO <200 mL/kg/min at 1 hour and critically lowLVO at the time of clinical deterioration was high. In addi-tion, the sensitivity of this threshold for other indices ofPLCS was high, suggesting that it may be a reliable screeningtool. The magnitude of this association led to modification ofthe postoperative clinical care pathway to incorporate TnE-CHO in refining clinical decision making.

Milrinone is a selective phosphodiesterase III inhibitorthat acts by increasing intracellular levels of cyclic adenosinemonophosphate. Established pharmacologic effects includepositive inotropy, lusitropy, and pulmonary and peripheralvasodilation.17,18 Milrinone improves mortality by prevent-ing low cardiac output in neonates and young children aftercardiac surgery.19 Given the known pathophysiology ofPLCS, milrinone is considered a biologically plausible agentfor targeted intervention, by virtue of its vasodilator andinotropic properties. One of our a priori concerns with mil-rinone is the effect of excessive vasodilation on a preload-compromised myocardium. Other theoretical adverse effectsof milrinone in preterm infants include bleeding from plate-let dysfunction. Neither complication was observed in any ofthe treated infants in our study.

In study B, we chose to match patients in both epochs ac-cording to gestational age at birth and LVO at 1 hour postli-gation. This was considered important because both epochswere inherently different. In addition, matching ensuredcomparable illness severity between groups. It should benoted that the predictive value of the 1-hour LVO evaluationwas further confirmed in epoch 2. All but 1 infant with anLVO >200 mL/kg/min remained hemodynamically stable.That infant had an LVO of 236 mL/kg/min with no evidenceof myocardial dysfunction at 1 hour postligation, but devel-oped systolic and diastolic hypotension with severe oxygena-tion failure by 8 hours. The hypotension was refractory tovolume and inotropic agents but responded well to hydro-cortisone, suggesting an alternative physiological process,such as vasodilation.Along with the well-recognized challenges of functional

echocardiography measurements, this study had other limi-tations. First, there might have been patient selection bias.Epoch 1 included only those patients who consented for 2previous echocardiography studies in this population,whereas epoch 2 was all-inclusive. In addition, there maybe other important unaccounted differences between groups.Second, postoperative outcomes might have been affected byclinical practice differences among neonatologists, evolutionof the PDA ligation team, or other unaccounted-for practicechanges. Nevertheless, the preoperative care of infants under-going PDA ligation is highly standardized at our center sincethe creation of a dedicated PDA ligation team under leader-ship of a single staff neonatologist (P.M.) in 2005. Preopera-tive stabilization and surgical and anesthetic managementdid not differ between the 2 epochs; details have been re-ported previously.11 Third, the dosing of milrinone was ex-trapolated from pharmacokinetic data for infants andchildren undergoing cardiac surgery.20 Mindful of the theo-retical risk of increased side effects in preterm infants, wechoose not to give a loading dose and added a slow bolusof 10 mL/kg of normal saline solution to the milrinone infu-sion. Whether the lack of side effects seen in the present studywas related to these interventions cannot be established. A re-cent pharmacokinetic study of milrinone in preterm infantsused a dose similar to that used in the present study.21

Fourth, given the design of our study, we can only hypothe-size as to themechanism of action of milrinone leading to im-proved stability. However, a recently published case reportprovided detailed pretreatment and posttreatment TnECHOindices in a preterm infant treated with milrinone after PDAligation.22 TnECHO performed 6 hours after initiation ofmilrinone infusion demonstrated improved indices of left

Table III. Primary and secondary outcomes in epochs 1 and 2

PLCS Need for inotropes Ventilation failure Oxygenation failure Need for steroids

Epoch 1 (n = 25), n (%) 11 (44) 14 (56) 12 (48) 13 (52) 4 (16)Epoch 2 (n = 27), n (%) 3 (11) 5 (19) 4 (15) 7 (26) 0P value .01 .01 .02 .08 .03

PLCS is defined as a composite outcome of the need for inotropic agents and either oxygenation or ventilation failure in the absence of any other identifiable etiology.


588 Jain et al


25


• Targeted initiation of intravenous milrinone based on NPE (LVO <200 mL/kg/min @ 1 hr after ligation)

• Despite prophylactic milrinone in selected patient in about 50% still develop oxygenation or ventilatory failure!

• A preoperative prolonged IVRT (isovolemic relaxation time), anindicator of diastolic dysfunction, was identified as an additionalrisk factor for PLCS

Ting JY, Resende M, More K, Nicholls D, Weisz DE, El-Khuffash A, et al. Predictors of respiratoryinstability in neonates undergoing patient ductus arteriosus ligation after the introduction of

targeted milrinone treatment. J Thorac Cardiovasc Surg. 2016;152(2):498-504.


boluses, inotropic support, or hydrocortisone were requiredwithin the first 24-hour postoperative period. The incidenceof PLCS in patients receiving and not receiving milrinonewere 12.2% (6/43) and 2.7% (1/37), respectively. Infantsreceiving milrinone prophylaxis were those who were athigh risk of developing PLCS (ie, LVO at 1-hour postoper-ative echocardiogram<200 mL/kg/min).

DISCUSSIONThe introduction of early postoperative TnECHO

screening and targeted milrinone treatment was followedby a reduction in the incidence of PLCS to 8.1%, whichis lower than previous reports.11,14 Despite this practicechange, the incidence of OF or VF remained high(51.2%) in this 4-year cohort. Targeted milrinone treatmenthas reduced the hypotension component of the syndrome,but the respiratory component is still a challenge to manage.The demographic profile of neonates who developed respi-ratory deterioration was discordant with the published liter-ature. Previous evidence suggested that the most vulnerablegroup were neonates less than 28 days old or less than1000 g at the time of surgery.10,13 Unlike previous studies,the postoperative course of neonates in our cohort was

characterized by OF or VF without hemodynamicinstability, the incidence of which is greatest withprolonged IVRT on preoperative echocardiogram.

Clinical decision-making processes related to theselection of neonates for PDA ligation and postoperativemanagement are highly variable among neonatologists.1

Although surgical ligation reduces the overall mortalityand facilitates extubation in babies with established LVoverload, recent evidence14,15 suggests an associationwith increased neurodevelopmental impairment, chroniclung disease, and severe retinopathy of prematurity afteradjusting for various confounding factors. Somecommentators advocate a less aggressive approachbecause of the association with adverse compositeoutcomes.16-18 Previous reports from our center showedthat the incidence of PDA ligation among prematurebabies born at less than 30 weeks of gestational agedecreased substantially from 10.7% in 2003 to 2005(epoch I) to 5.3% in 2010 to 2012 (epoch II); in addition,patients in the second epoch had greater preproceduralillness severity.19 To justify a causal relationship betweenPDA ligation and these morbidities, it is essential todetermine mechanistically how the surgery induces aprofound and lasting cascade of adverse end-organ effects.An alternative explanation is that these morbidities maysimply be surrogate markers for increased illness severityor may reflect higher grades of PDA shunt volume.15,20

Retrospective studies have failed to identify any relation-ship between surgical technique, anesthetic approach, orintraoperative fluid management to the development ofhypotension.7,12,21 Surgical ligation of a PDA leads to

TABLE 3. Logistic regression model for risk factors for development

of oxygenation failure or ventilation failure

Parameter

Odds ratio (95%

confidence interval)

P

value

Gestational age (w) 0.903 (0.607-1.343) .614

Preoperative IVRT (milliseconds) 1.090 (1.031-1.153) .002

PDA size (mm) 1.430 (0.474-4.319) .526

Preoperative MAP (cm H2O) 1.215 (0.879-1.679) .238

Postoperative LVO at 1-h (mL/kg/min) 0.991 (0.981-1.001) .073

Age of surgery (d) 1.137 (0.824-1.570) .435

Omnibus likelihood ratio: c2! 16.297 (degree of freedom! 6); P! .012; Hosmer &Lemeshow test: P ! .722. IVRT, Isovolumic relaxation time; PDA, patent ductusarteriosus; MAP, mean airway pressure; LVO, left ventricular output.

FIGURE 1. Isovolumic relaxation time (IVRT) to predict postoperative

respiratory instability.

FIGURE 2. Isovolumic relaxation time (IVRT) to predict postoperative

respiratory instability.

Congenital: Ductus Arteriosus Ting et al

502 The Journal of Thoracic and Cardiovascular Surgery c August 2016

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IVRT >30 msecAUC 0.75

Se 0.83Sp 0.61

The medians of differences between pre- and postoperativeIVRT in infants with and without OF or VF were 14milliseconds (IQR, 7-24) and 27 milliseconds (IQR,8-41), respectively, and the difference between the 2 groupswas not statistically significant (P ! .107).

Predictors of Respiratory InstabilityLogistic regression modeling was performed to identify

clinical and echocardiographic predictors of respiratoryinstability (OF or VF) (Table 3), which explained 30.9%of variance (Nagelkerke R2 ! 0.309) and correctlyclassified 72.6% of all cases. The following predictorswere entered into this model: gestational age, preoperativeIVRT, size of PDA, MAP before surgery, age of surgery,and LVO at 1 hour postoperatively. Prolonged IVRT waspredictive of respiratory instability (P ! .002) (Figure 1)and lower LVO showed a trend towards increased likelihoodof developing it (P ! .073).

IVRT yielded an area under the curve of 0.753 (95%confidence interval, 0.635-0.871; P<.001) for predictingdevelopment of OF or VF, with a cutoff value of 30milliseconds, providing a sensitivity of 82.9% andspecificity of 60.6% (Figure 2). The positive predictivevalue of an IVRT more than 30 milliseconds to predictdevelopment of OF or VF was 69.0%.

PLCSIn our cohort, only 7 (8.1%) infants developed PLCS.

Their median birth weight and gestational age were 760 g(range, 600-940) and 25 weeks (range, 24-26), respectively.Medians (and ranges) of age, corrected gestational age, andweight at surgery were 30 (22-62) days, 29 (28-34) weeks,and 1030 (780-1792) g, respectively. Their median LVO at1 hour after operation was 155 mL/kg/min (range, 86-270).All except 1 received milrinone prophylaxis, who had aLVO of 270 mL/kg/min at 1 hour after operation. Fluid

TABLE 1. Demographic and clinical characteristics of infants with postoperative respiratory instability

No OF or VF OF or VF P value

Number of patients 42 44

Gestational age (w)* 25 (25-27) 25 (24-26) N/A

Birth weight (g)* 725 (639-915) 745 (640-809) N/A

Gender (male), n (%) 19/42 (45.2) 20/44 (45.5) N/A

Apgar score at 5 min 7 (5-8) 6 (5-8) N/A

Antenatal steroids, n (%)y 16/38 (42.1) 20/33 (39.4) N/A

Intraventricular hemorrhage grades 3 or 4, n (%) 6/42 (14.3) 4/44 (9.1) .453

Necrotizing enterocolitis, n (%)z 11/42 (26.2) 13/43 (30.2) .679

Age at surgery (days of life)* 26 (20-38) 33 (25-40) .057

Corrected gestational age at surgery (w)* 30 (28-31) 30 (29-31) .740

Weight at surgery (g)* 960 (892-1230) 1055 (896-1366) .238

Preoperative mean airway pressure (mm Hg)* 9.0 (8.1-10.0) 9.0 (8.0-11.0) .809

Preoperative FIO2 (%)* 29 (24-40) 31 (27-40) .101

Post-ACTH stimulation test cortisol<500 nmol/L, n (%)x 6/30 (20.0) 6/35 (17.1) .767

Post-ACTH stimulation test cortisol<750 nmol/L, n (%)x 15/30 (50.0) 18/35 (51.4) .909

Preoperative inotropic use, n (%) 5/42 (11.9) 2/44 (4.5) .260

Milrinone treatment, n (%) 20/42 (47.6) 29/44 (69.5) .087

OF, Oxygenation failure; VF, ventilation failure; N/A, not applicable (baseline demographic characteristics); FIO2, fraction of inspired oxygen; ACTH, adrenocorticotropichormone. *Median (25th centiles, 75th centiles). yDefined as 2 or more doses; only 71 infants with complete information. zOne missing value. x65 infants had ACTH stimulationtest performed.

TABLE 2. Echocardiographic characteristics of infants with postoperative respiratory instability

No OF or VF OF or VF P value

Total number of patients 42 44

Preoperative LVO (mL/kg/min) 442 (354-548) (32 infants) 444 (342-557) (37 infants) .889

Preoperative IVRT (milliseconds) 30 (26-39) (33 infants) 44 (30-50) (35 infants) <.001

Preoperative E/A ratio 0.90 (0.83-1.10) (35 infants) 0.83 (0.79-0.97) (37 infants) .037

Preoperative LVFS (%) 40 (33-45) (29 infants) 38 (36-45) (33 infants) .877

Preoperative PDA size (mm) 2.8 (2.5-3.2) (41 infants) 2.8 (2.6-3.1) (42 infants) .993

Postoperative LVO (mL/kg/min) 212 (178-251) (42 infants) 188 (156-230) (44 infants) .088

Postoperative IVRT (milliseconds) 58 (47-74) (35 infants) 60 (54-72) (37 infants) .260

Postoperative E/A ratio 0.86 (0.73-1.00) (32 infants) 0.86 (0.71-1.00) (38 infants) .925

Postoperative LVFS (%) 28 (22-36) (26 infants) 30 (25-33) (30 infants) .711

Expressed as median (25th centiles, 75th centiles).OF, Oxygenation failure; VF, ventilation failure; LVO, left ventricular output; IVRT, isovolumic relaxation time; E/A, early-to-late-ventricular-filling velocities; LVFS, left ventricular fractional shortening; PDA, patent ductus arteriosus.

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Retrospective cohort study (199 infants, 512 echo’s)

Role of NPE in Neonatal CareBenefits? Impact on clinical managment

El-Khuffash A, Herbozo C, Jain A, Lapointe A, McNamara PJ. Targeted neonatal echocardiography (TnECHO) service in a Canadian neonatal intensive care unit: a 4-year experience. J Perinatol. 2013;33(9):687-90.

ORIGINAL ARTICLE

Targeted neonatal echocardiography (TnECHO) service in aCanadian neonatal intensive care unit: a 4-year experienceA EL-Khuffash1,6, C Herbozo2,6, A Jain2,3, A Lapointe2 and PJ McNamara2,3,4,5

OBJECTIVE: To characterize the effect of a targeted neonatal echocardiography (TnECHO) program on decision making in a tertiarylevel unit.STUDY DESIGN: Retrospective cohort study of neonates, admitted between September 2007 and April 2011. Details of theTnECHO, and the clinical decisions within 6 h of the consultation were recorded.RESULT: A total of 199 infants underwent 512 echocardiograms with a median (interquartile range) of 2 (1 to 3) TnECHO studies perinfant. The indications included assessment for patent ductus arteriosus (PDA; n! 261, 51%), post-PDA ligation assessment(n! 101, 19%), pulmonary hemodynamics (n! 81, 16%), myocardial performance and systemic blood flow (n! 52, 10%), andcentral venous catheter tip position (n! 6, 1%). TnECHO consultation was followed by a change in clinical management in 212cases (41%) and avoidance of a planned intervention in 112 cases (22%).CONCLUSION: TnECHO may be a useful tool to guide clinical decisions in the neonatal intensive care unit setting. Well-plannedprospective studies are needed to assess the impact of TnECHO on outcomes.

Journal of Perinatology advance online publication, 25 April 2013; doi:10.1038/jp.2013.42

Keywords: echocardiography; neonate; intensive care

INTRODUCTIONThe use of targeted neonatal echocardiography (TnECHO) forthe evaluation of the cardiovascular wellbeing is gaining interest.The purpose of TnECHO is to provide physiological informationin real time, in order to support clinical decision making.1

This approach is designed to enhance clinical judgment, providea better understanding of active physiological processes andmonitor the response to treatment. Combination of clinicalexamination and bedside echocardiography has been shownto improve clinical diagnosis and patient management.2 Inadult intensive care units, use of trans-esophageal echo-cardiography is common practice and has been shown tochange the clinical management in up to 30% of patientsbased on the results; in an additional 10% of patients it maydetect severe previously unknown diagnoses.3 There is someevidence that routine use of TnECHO in the neonatal unitmay lead to identification of cardiovascular compromise,changes in management4 and potentially improve short-termoutcomes.5

A TnECHO service was first introduced to the Hospital for SickChildren (HSC), Toronto in 2006. Recent published guidelineson training and standards for clinical practice have led torefinement of this program and more integration with the localpediatric cardiology service.6 The purpose of this study wasto review and describe the TnECHO service, identify theindications for performing a TnECHO and assess its potentialeffect on clinical decision making at our center over a 4-yearperiod.

METHODSThis was a retrospective audit of neonates admitted to theneonatal intensive care unit (NICU) at the HSC, who received aTnECHO examination, between September 2007 and April 2011.The HSC is a 36 bed quaternary out-born referral NICU serving thegreater Toronto area in Canada. In addition to extreme prematureinfants, the unit caters for term or preterm neonates with any typeof acute medical or surgical illness, the exception being terminfants with exclusive congenital heart defects or diaphragmatichernias. The electronic patient health record system was used toidentify infants that underwent TnECHO consultation by anexperienced neonatologist.

The clinical team managing the infant usually requests aTnECHO consultation to support clinical judgment, provide novelphysiological insights that may aid in the infants’ management orto guide therapeutic interventions such as the use of non-steroidalanti-inflammatory drugs and inotropes. A TnECHO consultation isdefined as a detailed clinical appraisal of cardiorespiratorywellbeing, followed by a structured and comprehensive echocar-diogram to assess myocardial performance and hemodynamics.All TnECHO evaluations including measurements of all the variousparameters were conducted in accordance to specific protocolsdrafted by our center and detailed elsewhere.1 The echo-cardiography information is then carefully integrated within theclinical context to reach a diagnosis or clinical impression,leading to the formulation of a therapeutic recommendation.The decision to request a TnECHO consultation and to acceptits recommendations was at the discretion of the attending

1Department of Paediatrics, The Rotunda Hospital, Dublin, Ireland; 2Department of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada; 3Division ofNeonatology, Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada; 4Department of Physiology, University of Toronto, Toronto, Ontario, Canada and5Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. Correspondence: Dr PJ McNamara, Department of Neonatology, Hospital forSick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada.E-mail: [email protected] first authors.Received 9 January 2013; revised 27 February 2013; accepted 15 March 2013

Journal of Perinatology (2013), 1–4& 2013 Nature America, Inc. All rights reserved 0743-8346/13

www.nature.com/jp

neonatologist. Institutional ethics board approval was obtainedbefore commencing this study.

We evaluated the following outcomes: trends in annual ratesand indications for TnECHO-based consultations; frequency ofevents where TnECHO led to a change in management and/orclinical improvement; number of times TnECHO resulted inavoiding an unnecessary intervention; and the frequency ofunexpected findings resulting in a potentially beneficialintervention.

Data collectionThe following patient demographics were recorded; gestation,birth weight, type of delivery, antenatal morbidity and history,Apgar scores, and gender. Information was collected about theactive clinical issue and disease states at the time of TnECHO. Theamount of cardiorespiratory support, for example, ventilationrequirement, need for inotropes and nitric oxide use wererecorded 1-h before and 6-h after TnECHO evaluation.

Echocardiography examinations were performed using either theM-Turbo portable ultrasound (Sonosite, Bothell, Washington, USA)or the Vivid 7 echocardiography machine (GE, Waukesha, WI, USA).These evaluations were performed as part of a hemodynamicconsultation when requested by the attending physician. The usualindications for TnECHO included patent ductus arteriosus (PDA)assessment, assessment of myocardial performance and systemicblood flow (including postoperative assessment of infants followingPDA ligation), assessment of pulmonary hypertension and assess-ment of peripherally inserted central catheters tip position. Theindication for TnECHO and the active patient morbidity at the timeof the consultation were recorded. All scans were performed byneonatologists with extensive training in echocardiography (PJM,AEL-K and AJ) or by fellows in training under their supervision.All scans were reported in real time by an attending neonatologist(PJM), dedicated to this service. The results of the consultation andany study recommendations were communicated directly to theclinical team and documented in the electronic patient chart. Allstudies were archived on expandable storage off the machines. Thescans were all performed according to unit-specific standardizedprotocols. Follow-up scans to assess treatment response wereperformed according to the clinical situation.

The impact of each TnECHO evaluation on clinical practice wasdocumented and categorized into one of the following categories:unexpected diagnosis: defined as a novel physiological insight notanticipated or suspected by clinical examination; change inmanagement: defined as the institution of a new therapeuticintervention as guided by the findings of the TnECHO andconfirming clinical suspicion; avoidance of a planned intervention:defined as stopping a planned therapeutic intervention (put inplace following clinical assessment) after the findings of theTnECHO; monitoring treatment response: defined as the use ofTnECHO to either escalate or wean therapy already instituted; andno new physiologic insights defined by an unremarkable TnECHO,which did not result in any of the former outcomes. Descriptivestatistics were used to summarize the data using SPSS (version 20,IBM, Armonk, NY, USA).

RESULTSA total of 199 infants underwent 512 echocardiography assess-ments from September 2007 to April 2011. The median (range)gestation and weight at birth were 27.6 (23.0 to 41.7) weeks and1155 (477 to 5005) grams, respectively. The majority of infants(n! 121, 62%) were under 28 weeks gestation at birth. Theechocardiography assessments were performed at a median ageof 6 (1 to 147) days. The most common (n! 153, 77%) primarydiagnosis at admission was prematurity and respiratory distresssyndrome; 15 (8%) were admitted with a primary diagnosis

of hypoxic ischemic encephalopathy; 12 (6%) with persistentpulmonary hypertension of the newborn; 8 infants (4%) wereadmitted for management of necrotizing enterocolitis or sepsiswith hemodynamic instability; and 11 (5%) with other diagnoses.There were 8 studies in the last 4 months of 2007, 24 studies in2008, 156 studies in 2009, 264 studies in 2010 and 60 studies inthe first in the first trimester of 2011. Sixty-two percent of infantshad more than one TnECHO evaluation. Each infant underwent amedian of 2 (1 to 15) scans.

Table 1 shows the indications for TnECHO consultation. Themajority of infants underwent an echocardiogram for assessmentof PDA significance or for guiding cardiovascular care followingPDA ligation. This comprised of 362 (70.7%) of the TnECHOsperformed during the study period. TnECHO resulted in a changein management after 212 (41%) consultations; the most commonof decisions related to choice of inotrope therapy and PDA care.Table 2 shows the specific interventions that were temporallyrelated to TnECHO. In addition, a planned intervention, wasavoided in a further 112 (22%) of consultations. The purpose of 88(17%) TnECHO consultations were to monitor treatment response.An unexpected diagnosis occurred in 31 (6%) of cases.

DISCUSSIONThe use of real-time TnECHO to guide cardiovascular care hasbecome an integral component of NICU practice. This is the firstdescriptive report of a dedicated TnECHO service, led byneonatologists, and its influence on cardiovascular decisionmaking. The annual increase in requests for TnECHO consultationis suggestive of adoption of the practice by neonatologists as anintegral component of NICU care.

We identified changes in clinical decisions temporally asso-ciated with TnECHO consultations. These included change inmanagement in 40% of infants and avoidance of a plannedintervention in an additional 20% of cases. The commonestcondition associated with change in management was a PDA. Thechanges included withholding of medical treatment when theshunt volume was shown to be low. In four cases, PDA ligationwas deferred on the day of the procedure. In all cases, the patientsreturned to their primary NICU and did not require subsequent

Table 1. Indication of echo (n! 512)

Frequency Percent

PDA assessment 261 51.0Assessment of PLCS 101 19.7Assessment of pulmonary hemodynamics 81 15.8Assessment of myocardial performance 52 10.2PICC line position 6 1.2Research/teaching echo 11 2.2

Abbreviations: PDA, patent ductus arteriosus; PICC, peripherally insertedcentral catheters; PLCS, post-ligation cardiac syndrome.

Table 2. Specific interventions

Frequency Percent

Guiding inotrope therapy 120 40Surgical PDA ligation 56 18NSAID treatment for PDA 50 16Bolus of fluids 35 12Guiding nitric oxide therapy 31 10Diuretics/other 13 4

Abbreviations: NSAIDS: non-steroidal anti-inflammatory drugs; PDA, patentductus arteriosus.

Neonatal echocardiography in the NICUA EL-Khuffash et al

2

Journal of Perinatology (2013), 1 – 4 & 2013 Nature America, Inc.

neonatologist. Institutional ethics board approval was obtainedbefore commencing this study.

We evaluated the following outcomes: trends in annual ratesand indications for TnECHO-based consultations; frequency ofevents where TnECHO led to a change in management and/orclinical improvement; number of times TnECHO resulted inavoiding an unnecessary intervention; and the frequency ofunexpected findings resulting in a potentially beneficialintervention.

Data collectionThe following patient demographics were recorded; gestation,birth weight, type of delivery, antenatal morbidity and history,Apgar scores, and gender. Information was collected about theactive clinical issue and disease states at the time of TnECHO. Theamount of cardiorespiratory support, for example, ventilationrequirement, need for inotropes and nitric oxide use wererecorded 1-h before and 6-h after TnECHO evaluation.

Echocardiography examinations were performed using either theM-Turbo portable ultrasound (Sonosite, Bothell, Washington, USA)or the Vivid 7 echocardiography machine (GE, Waukesha, WI, USA).These evaluations were performed as part of a hemodynamicconsultation when requested by the attending physician. The usualindications for TnECHO included patent ductus arteriosus (PDA)assessment, assessment of myocardial performance and systemicblood flow (including postoperative assessment of infants followingPDA ligation), assessment of pulmonary hypertension and assess-ment of peripherally inserted central catheters tip position. Theindication for TnECHO and the active patient morbidity at the timeof the consultation were recorded. All scans were performed byneonatologists with extensive training in echocardiography (PJM,AEL-K and AJ) or by fellows in training under their supervision.All scans were reported in real time by an attending neonatologist(PJM), dedicated to this service. The results of the consultation andany study recommendations were communicated directly to theclinical team and documented in the electronic patient chart. Allstudies were archived on expandable storage off the machines. Thescans were all performed according to unit-specific standardizedprotocols. Follow-up scans to assess treatment response wereperformed according to the clinical situation.

The impact of each TnECHO evaluation on clinical practice wasdocumented and categorized into one of the following categories:unexpected diagnosis: defined as a novel physiological insight notanticipated or suspected by clinical examination; change inmanagement: defined as the institution of a new therapeuticintervention as guided by the findings of the TnECHO andconfirming clinical suspicion; avoidance of a planned intervention:defined as stopping a planned therapeutic intervention (put inplace following clinical assessment) after the findings of theTnECHO; monitoring treatment response: defined as the use ofTnECHO to either escalate or wean therapy already instituted; andno new physiologic insights defined by an unremarkable TnECHO,which did not result in any of the former outcomes. Descriptivestatistics were used to summarize the data using SPSS (version 20,IBM, Armonk, NY, USA).

RESULTSA total of 199 infants underwent 512 echocardiography assess-ments from September 2007 to April 2011. The median (range)gestation and weight at birth were 27.6 (23.0 to 41.7) weeks and1155 (477 to 5005) grams, respectively. The majority of infants(n! 121, 62%) were under 28 weeks gestation at birth. Theechocardiography assessments were performed at a median ageof 6 (1 to 147) days. The most common (n! 153, 77%) primarydiagnosis at admission was prematurity and respiratory distresssyndrome; 15 (8%) were admitted with a primary diagnosis

of hypoxic ischemic encephalopathy; 12 (6%) with persistentpulmonary hypertension of the newborn; 8 infants (4%) wereadmitted for management of necrotizing enterocolitis or sepsiswith hemodynamic instability; and 11 (5%) with other diagnoses.There were 8 studies in the last 4 months of 2007, 24 studies in2008, 156 studies in 2009, 264 studies in 2010 and 60 studies inthe first in the first trimester of 2011. Sixty-two percent of infantshad more than one TnECHO evaluation. Each infant underwent amedian of 2 (1 to 15) scans.

Table 1 shows the indications for TnECHO consultation. Themajority of infants underwent an echocardiogram for assessmentof PDA significance or for guiding cardiovascular care followingPDA ligation. This comprised of 362 (70.7%) of the TnECHOsperformed during the study period. TnECHO resulted in a changein management after 212 (41%) consultations; the most commonof decisions related to choice of inotrope therapy and PDA care.Table 2 shows the specific interventions that were temporallyrelated to TnECHO. In addition, a planned intervention, wasavoided in a further 112 (22%) of consultations. The purpose of 88(17%) TnECHO consultations were to monitor treatment response.An unexpected diagnosis occurred in 31 (6%) of cases.

DISCUSSIONThe use of real-time TnECHO to guide cardiovascular care hasbecome an integral component of NICU practice. This is the firstdescriptive report of a dedicated TnECHO service, led byneonatologists, and its influence on cardiovascular decisionmaking. The annual increase in requests for TnECHO consultationis suggestive of adoption of the practice by neonatologists as anintegral component of NICU care.

We identified changes in clinical decisions temporally asso-ciated with TnECHO consultations. These included change inmanagement in 40% of infants and avoidance of a plannedintervention in an additional 20% of cases. The commonestcondition associated with change in management was a PDA. Thechanges included withholding of medical treatment when theshunt volume was shown to be low. In four cases, PDA ligationwas deferred on the day of the procedure. In all cases, the patientsreturned to their primary NICU and did not require subsequent

Table 1. Indication of echo (n! 512)

Frequency Percent

PDA assessment 261 51.0Assessment of PLCS 101 19.7Assessment of pulmonary hemodynamics 81 15.8Assessment of myocardial performance 52 10.2PICC line position 6 1.2Research/teaching echo 11 2.2

Abbreviations: PDA, patent ductus arteriosus; PICC, peripherally insertedcentral catheters; PLCS, post-ligation cardiac syndrome.

Table 2. Specific interventions

Frequency Percent

Guiding inotrope therapy 120 40Surgical PDA ligation 56 18NSAID treatment for PDA 50 16Bolus of fluids 35 12Guiding nitric oxide therapy 31 10Diuretics/other 13 4

Abbreviations: NSAIDS: non-steroidal anti-inflammatory drugs; PDA, patentductus arteriosus.

Neonatal echocardiography in the NICUA EL-Khuffash et al

2

Journal of Perinatology (2013), 1 – 4 & 2013 Nature America, Inc.

TnECHO consultation was followed by a change in clinical management in 212 cases (41%) and avoidance of a

planned intervention in 112 cases (22%)

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Corredera A, Rodriguez MJ, Arevalo P, Llorente B, Moro M, Arruza L. [Functionalechocardiography in neonatal intensive care: 1 year experience in a unit in Spain]. An

Pediatr (Barc). 2014;81(3):167-73.

Role of NPE in Neonatal CareBenefits? Impact on clinical management

Retrospective analysis168 NPE studies in 50 patients in 1 year

mGA 31.3 (24,1-40.2) weeksmPNA 6 (2-19) daysIndications for NPE (n=168):

• PDA (58.3%)• Haemodynamic instability (22.2%)• Presence of heart murmur (8.3%)• Foeto-neonatal transition (5.4%)• PPHN (1.2%)• Other (4.8%) Modification of treatment

in (62/168) 36.9%

28


• Retrospective cohort study• NPE in 154 preterm infants

<29 weeks’ gestation on 1st

DOL• Unexpected findings in 30%

of patients• UVC in malposition (28%)• CHD (10%)• Unexpected PH (3%)• Pericardial effusion (2%)

Role of NPE in Neonatal CareBenefits? Unexpected findings

Four incidental liver hematomas were identified andwere associated with malpositioned umbilical venouscatheters (Figure 2). The identification of the liver hem-atomas prompted the removal of the catheters foundadjacent to the lesions. All 4 neonates had full recoverywith resolution of the hematomas before discharge. Theremainder of the findings included pericardial effusions(which subsequently resolved spontaneously) and unex-pected PH, with suprasystemic pulmonary pressures(Table 2). Two of the neonates identified as having PHsubsequently received inhaled nitric oxide for an increas-ing oxygen requirement with good recovery.

The presence of unexpected findings on targetedneonatal echocardiography was independently associ-ated with a combined outcome of chronic lung diseaseor death when controlling for gestation, sex, 5-minuteApgar score, chorioamnionitis, preeclampsia, and the useof antenatal steroids (adjusted odds ratio, 4.3 [95% con-fidence interval, 1.5–12.4]; P 5 .007).

Discussion

This study identified the presence of a relatively highrate of asymptomatic abnormalities and incidentalfindings on screening echocardiograms. Those includedmalpositioned umbilical venous catheters and their com-plications, cyanotic and acyanotic CHD, severe PH, andpericardial effusions. Interestingly, malpositioned umbili-cal venous catheters were more likely to be placed in theleft, rather than the right, atrium. Neonates with unex-pected findings had an earlier gestation and lower birthweight, required a longer time to attain full enteral feeds,had a longer hospital admission, and had an increasedincidence of CLD and death before discharge.

Echocardiography has been used since the 1980s toexamine umbilical vascular catheter positions.9,10 Ensur-ing correct umbilical catheter placement is critical, aspotential complications of an erroneous position includeintracardiac thrombosis (Figure 3), endocarditis, arr-hythmias, myocardial perforation, pericardial effusion,low cardiac output, and liver hematomas.11–15 Severalstudies have demonstrated that ultrasonography andechocardiography are superior to radiography for localiz-ing the umbilical catheter tip.9,11,16–21 Ades et al11

Figure 1. Umbilical venous catheter tip (arrows) situated in the left atrium on both the short-axis parasternal and apical 4-chamber views.

Table 2. Rates and Types of Unexpected Findings

Complication n (%)

Overall unexpected findings 54 (37)Neonates with unexpected findings 43 (30)Neonates with an umbilical

venous catheter inserted87 (60)

Malpositioned umbilicalvenous catheter identifiedon echocardiography

24/87 (28)

Tip in left atrium 18/24 (75)Tip in right atrium 2/24 (8)Tip in liver 4/24 (17)Liver hematomas 4/87 (17)CHD 15 (10)Atrial septal defect, median

(interquartile range), mm7/15 (47),

5.2 (4.5–5.2)Ventricular septal defect, median

(interquartile range), mm4/15 (27),

2.3 (1.7–3.1)Pericardial effusion 3 (2)Unexpected PH 5 (3)

Unless stated, the denominator for the values is 145.

Smith et al—Incidental Findings on Neonatal Echocardiography

846 J Ultrasound Med 2018; 37:843–849

Smith A, Breatnach CR, James AT, Franklin O, El-Khuffash A. Incidental Findings on Routine Targeted Neonatal Echocardiography Performed in Preterm Neonates Younger Than 29 Weeks'

Gestation. J Ultrasound Med. 2018;37(4):843-9.

29


Shah DM, Kluckow M. Early functional echocardiogram and inhaled nitric oxide: usefulnessin managing neonates born following extreme preterm premature rupture of membranes

(PPROM). J Paediatr Child Health. 2011;47(6):340-5.

Role of NPE in Neonatal CareBenefits? Impact on outcome

Retrospective cohort study15 extremely preterm infants

GA 27.8±5.3 weeks; BW 1207±783 g

30


• Retrospective epoch study to study the impact of Integrated Evaluation of Hemodynamics (IEH) in 340 newborns with compromised hemodynamics• Epoch 1 (Jan ‘12 - Mar ‘14): no IEH• Epoch 2 (Apr ‘14 – Dec ‘15): IEH

• Primary outcome: time to recovery


Elsayed YN, Amer R, Seshia MM. The impact of integrated evaluation of hemodynamics usingtargeted neonatal echocardiography with indices of tissue oxygenation: a new approach. J

Perinatol. 2017;37(5):527-35.

ORIGINAL ARTICLE

The impact of integrated evaluation of hemodynamics usingtargeted neonatal echocardiography with indices of tissueoxygenation: a new approachYN Elsayed, R Amer and MM Seshia

OBJECTIVE: To study the impact of integrated evaluation of hemodynamics (IEH) using targeted neonatal echocardiography,together with regional tissue oxygenation, fractional oxygen extraction using near-infrared spectroscopy on the management ofinfants with compromised hemodynamics.STUDY DESIGN: Retrospective cohort comparison of two groups of infants with compromised hemodynamics. EPOCH 1: did notundergo IEH (January 2012 to March 2014); EPOCH 2: underwent IEH (April 2014 to December 2015). The primary outcome was thetime to recovery.RESULTS: In all, 340 infants were included; 158 underwent IEH with a median (IQR) of 2 (1 to 3) evaluations per infant. Reasons forassessment included PDA (60%), compromised systemic circulation (14%) and clinically suspected pulmonary hypertension (22%).The time to recovery was shorter in IEH group in patients with compromised systemic circulation median (IQR), 32 h (24 to 63)compared with none IEH group 71 h (36 to 96), pulmonary hypertension 63 h (14.2 to 102) in IEH group compared with 68 h (24 to240) in none IEH group, there were fewer PDA-related complications in preterm infants with PDA in IEH group.CONCLUSION: IEH was associated with shorter time to clinical recovery in infants with compromised hemodynamics

Journal of Perinatology advance online publication, 19 January 2017; doi:10.1038/jp.2016.257

INTRODUCTIONIntact or normal hemodynamics implies blood !ow that providesadequate oxygen and nutrient delivery to the tissues.1 Blood !owvaries with vascular resistance and cardiac function; both may bere!ected in blood pressure.2 Normal cardiovascular dynamicsshould be considered within the context of global hemodynamicfunction, with the aim of achieving normal oxygen delivery andend-organ performance.3 The current routine assessment ofhemodynamics in sick preterm and term infants is based onincomplete information. We have addressed this by adopting anapproach utilizing objective techniques, namely integratingtargeted neonatal echocardiography (TNE) with near-infraredspectroscopy (NIRS). Implementation of these techniques requiresan individual with the requisite TNE training, preferably in anaccredited program, who also has a good understanding ofperinatal and neonatal cardiovascular, respiratory and otherspeci"c end-organ physiology.

Determining a neonate’s capacity to autoregulate is crucial inintegrated evaluation of hemodynamics (IEH). In this study, wedescribe the impact of integrating neonatal hemodynamics usingTNE with indices of tissue oxygenation within a tertiary neonatalintensive care unit. We have de"ned ‘intact hemodynamicsphysiology’ as the integrated ability of the cardiovascular system,the oxygen-carrying capacity of the blood and autoregulatorymechanisms to be adequate for normal end-organ function.4 TNEuses ultrasound to longitudinally assess myocardial performance,systemic and pulmonary blood !ow, as well as identifyingintracardiac and extracardiac shunts.5 It provides detailed real-time information concerning cardiovascular physiology, which

may lead to rapid identi"cation of the pathophysiology ofcirculatory failure in critically ill neonates such as those withsepsis or persistent pulmonary hypertension.6 NIRS cannotdiagnose speci"c pathophysiology, but it can alert the health-care team to early changes in tissue oxygenation.7 Abnormal NIRSreadings may re!ect other confounders that affect oxygendelivery such as hypocapnia, high mean airway pressure, lowhemoglobin or a hemodynamically signi"cant PDA; all of theseconfounders must be assessed when considering our integratedmodel and before relying on NIRS as a surrogate marker for blood!ow.8

By integrating information from the clinical examination, NIRS,and TNE a complete picture can be obtained.4 Autoregulationinvolves local vasodilation through the release of nitric oxide andother vasodilators. When autoregulation is compromised, there isan increase in tissue oxygen extraction.9 Thus increased fractionaloxygen extraction (FOE) can be regarded as a compensatory stepbefore the maximum oxygen extraction capacity being reachedresulting in ensuing lactic acidosis.10

The purpose of this study reports is to report preliminary resultsof the implementation of IEH in an neonatal intensive care unitand to examine whether IEH can improve the outcome ofnewborn infants with compromised hemodynamics.

METHODSInstitutional ethics board approval was obtained before commencing thisretrospective study of all infants with compromised hemodynamicsadmitted to the two neonatal intensive care units in Winnipeg betweenJanuary 2012 and December 2015. Retrospective chart review and

Section of Neonatology, Department of Paediatrics, University of Manitoba, Winnipeg, Manitoba, Canada. Correspondence: Dr YN Elsayed, Section of Neonatology, Department ofPaediatrics, University of Manitoba, MS361L-820 Sherbrook Street, 735 Notre Dame Ave., Winnipeg, Manitoba, Canada R3A1R9.E-mail: [email protected] 9 April 2016; revised 19 December 2016; accepted 22 December 2016

Journal of Perinatology (2017) 00, 1–9© 2017 Nature America, Inc., part of Springer Nature. All rights reserved 0743-8346/17

www.nature.com/jp

hemodynamics consultation records were used to identify all infants whounderwent IEH by a trained neonatologist11 from April 2014 to December2015 (EPOCH 2). Pharmacy’s electronic records of infants who receivedcardiovascular medications and section of respiratory therapy’s records ofinfants who received respiratory support and/or inhaled nitric oxide (iNO)were also reviewed. Similar chart and record review was made of all infantsadmitted with similar clinical conditions—as per inclusion criteria—between January 2012 to March 2014 (EPOCH 1) and who had notreceived IEH.

The decision to request IEH consultation in sick infants with suspectedcompromised hemodynamics was made by the clinical team. Figure 1shows the !ow charts with included and excluded infants for the threeclinical categories from both EPOCHS.

IEH is based on evaluation of components contributing to blood !owand tissue oxygenation as follows (Figure 2):

Figure 1. Flow chart of included and excluded cases for the three main categories: (a) compromised systemic circulation group, (b) pulmonaryhypertension group and (c) PDA group. Abbreviations: PS, pulmonary stenosis; RDS, respiratory distress syndrome; VSD, ventricular septaldefect.

Figure 2. Components of integrated evaluation of hemodynamics.

The impact of integrated evaluation of hemodynamicsYN Elsayed et al

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Journal of Perinatology (2017), 1 – 9 © 2017 Nature America, Inc., part of Springer Nature.31



Elsayed YN, Amer R, Seshia MM. The impact of integrated evaluation of hemodynamics usingtargeted neonatal echocardiography with indices of tissue oxygenation: a new approach. J

Perinatol. 2017;37(5):527-35.within 72 h after IEH), undetermined outcome including infantswith documented improvement after 72 h in 15% (potentialpositive outcome) and negative in 1%. Three patients continuedto deteriorate with irreversible shock despite implementing IEHrecommendation; two were surgical patients with bowel ischemia

demonstrated either by postmortem pathology or open surgery,probably due to reperfusion injury. Table 3 also shows the numberof infants with compromised autoregulation in each group. It isdif!cult to apply the same graded impact of regular clinical careon infants from EPOCH 1, but we have documented improvementshortly after the start of the management plan (within 72 h) in33.5% of the studied group.

DISCUSSIONThere is increasing recognition by neonatologists that the focus ofmonitoring systems must change from those of solely bloodpressure and arterial oxygen saturation monitoring to those thatmeasure organ perfusion and tissue oxygen delivery.10 Currentresearch con!rms that the measurement of blood pressure doesnot re"ect either tissue perfusion or oxygen delivery,18,19 andcurrent therapeutic interventions for hypotension are notassociated with improved in-hospital outcomes or neurodevelop-mental outcomes.20,21 Objective evaluation of hemodynamicsusing the newer techniques of TNE and NIRS have proven to bevaluable in evaluation of systemic blood "ow, pulmonary blood"ow, myocardial performance and tissue oxygen delivery;integrating TNE !ndings, NIRS and clinical parameters can re"ectthe integrity of autoregulatory mechanisms.10,15 Recent researchhighlighted the bene!cial use of coherence analysis of MABP andNIRS to predict changes in autoregulation in sick neonates.10,22,23

This new approach has the potential to positively impact decision-

Table 2. clinical characteristics of the study groups

EPOCH 1 (before IEH) EPOCH 2 (after IEH) P-value

Compromised systemic circulation in preterm infantsNumber of cases 29 21Birth weight (g) 802 (725–900.5) 790 (646–920) 0.12Gestation (weeks) 25 (24–27) 24.5 (24–27.7) 0.16Male sex 17 (58%) 11 (52%) 0.4Con!rmed systemic infection 11 (38%) 5 (25%) 0.2Mean blood pressure at 6 h (mmHg) 25 (25–28 24 (23–26) 0.25Mean blood pressure at 48 h (mmHg) 30 (26–32) 34 (23–38) 0.001Lactic acid at 6 h of intervention (mmol l! 1) 3 (1.25–4) 2 (1.8–3.75) 0.34Lactic acid at 48 h of intervention (mmol l! 1) 2 (1–3.75) 1 (0.7–1.4) o0.001Time to full recovery (hours) 71 (36–96) 32 (24–63) 0.013Deaths due to shock 8 (27.6%) 2 (10%) 0.12

PDA in preterm infants o29 weeksNumber of cases 89 77Echo studies 136 216Male sex 44 (49%) 41 (53%) 0.48Birth weight (g) 890 (720–1100) 910 (720–1052) 0.36Gestation (weeks) 26.4 (25–28) 26.2 (25–28.5) 0.42Medically treated 65 (72%) 63 (85%) 0.04PDA ligation 14 (15.7) 3(4%) o0.001Post PDA ligation syndrome 6 0 0.02Follow-up by echo after medical treatment course 45 (50.5%) 63 (79%) o0.001Chronic lung disease 34 (38%) 26 (34%) 0.33Retinopathy of prematurity requiring treatment 15 (19%) 11 (15%) 0.28IVH ( grade III to IV) 18 (20%) 12 (15.6%) 0.14

Pulmonary hypertensionNumber 64 45Gestation (weeks) 37 (36.2–38) 37.5 (35.4–38.5) 0.41Birth weight (g) 3170 (2800–4021) 3220 (2750–3970) 0.34Male sex 38 (59%) 25 (53%) 0.36OI before intervention 24 (18–27) 26 (19–29) 0.35OI 48 h after intervention 12 (9–15) 10 (7–12) 0.02Time to clinical recovery (hours) 68 (24–240) 63 (14.2–102) 0.02Unresponsive or inadequate response to iNO 21 (32.8%) 6 (13%) 0.04

Data are presented as median± IQR; P is bolded where signi!cant.

Figure 4. Cox proportional hazards of compromised systemiccirculation and compared time to clinical recovery in epochs 1 and 2(p=0.002.

The impact of integrated evaluation of hemodynamicsYN Elsayed et al

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Journal of Perinatology (2017), 1 – 9 © 2017 Nature America, Inc., part of Springer Nature.

IEH ⊝

IEH ⊕

Multivariable analysis, includingadjustment for confirmed infection and

gestational age: time to recovery remained significantly lower in EPOCH 2,

mean30.6h (95% CI, 13 to 59.8) compared with EPOCH 1, mean, 96.5h

(95% CI, 73.4 to 114.5) (P=0.002)

PretermShock

Conclusion: IEH was associated with shorter time to clinical recovery in infantswith compromised hemodynamics

32


Neonatologist Performed EchocardiographyHemodynamic Consultation

Hebert A, et al. Evolution of Training Guidelines for Echocardiography Performed by theNeonatologist: Toward Hemodynamic Consultation. J Am Soc Echocardiogr. 2019;32(6):785-90.

33


Neonatologist Performed EchocardiographyHemodynamic Consultation

Hem odynam ic instability, respiratory and/or clinical

deterioration

Hem odynam ic consultationrequest or perform ed by trained

attending neonatologist

Hem odynam ic consultation: m edical history, past andcurrent pharm acologicaltreatm ents, vital signs,

respiratory settings, laboratoryand im agery investigations,

physical exam

Indication to performechocardiography based on hem odynam ic consultation?

YES

NO

Recom m endations based on physiological and clinical

rational w ith clear explanationto the attending clinical team

Clinical follow-up andechocardiography follow-up if

indicated

Echocardiography perform andreview by hem odynam ic team

Recom m endations based on physiological and clinical and

echocardiographic rationalw ith clear explanation to the

attending clinical team

Clinical follow-up andechocardiography follow-up if

indicated

Hebert A, et al. Evolution of Training Guidelines for Echocardiography Performed by theNeonatologist: Toward Hemodynamic Consultation. J Am Soc Echocardiogr. 2019;32(6):785-90.

34


Neonatologist Performed EchocardiographySummary• Increasing interest in NPE in Europe• In order to maintain patient safety and ensure the

optimal use of this skill, adherence to training guidelines along with continued collaboration with our pediatric cardiology colleagues is of paramount importance

• Always be aware of your limitations• Any patient with suspected or confirmed structural

heart disease should be referred to a paediatriccardiologist

• NPE enables individualized, physiology-basedhaemodynamic management

35


Neonatologist Performed EchocardiographyPediatric Research 2018; 84 (S1): 1-88 (03 August 2018)

OPEN ACCESS

www.nature.com/collections/pjlqbgkmwk

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Neonatologist Performed EchocardiographyESPR – www.espr.eu

37

ANY QUESTIONS

Willem de BoodeDepartment of NeonatologyRadboudumc Amalia Children’s HospitalNijmegen, The Netherlands

[email protected]

38

http://radboudumc.nl

poznan role of npe wpdeboode [191130] - noworodek.edu.pl · 1department of neonatology, radboud...

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