CHHS18/115

Canberra Hospital and Health ServicesClinical Guideline Patent Ductus Arteriosus Assessment and TreatmentContents

Contents....................................................................................................................................1

Guideline Statement.................................................................................................................2

Scope........................................................................................................................................ 3

Section 1 – When to Treat and Scan.........................................................................................3

Section 2 – PDA Size and Flow Pattern......................................................................................5

Section 3 – Supportive Care......................................................................................................5

Section 4 – Medical Treatment.................................................................................................5

Section 5 – Surgical Treatment.................................................................................................6

Implementation........................................................................................................................ 6

Related Policies, Procedures, Guidelines and Legislation.........................................................7

References................................................................................................................................ 7

Search Terms............................................................................................................................ 8

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology1 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

CHHS18/115

Guideline Statement

BackgroundPatent Ductus Arteriosus Patent ductus arteriosus (PDA) is a wide muscular vessel between the pulmonary artery and the aorta. This vessel usually closes within 24 hours of birth in term infants but later in preterm infants, in response to an increase in arterial oxygen content and decrease in local and circulating prostaglandin E concentrations. Persistence in ductal opening coinciding with normal postnatal fall in pulmonary vascular resistance (PVR) results in left to right shunting across the PDA. The consequences may include pulmonary over-perfusion and/or systemic hypoperfusion.

Ibuprofen and IndomethacinInhibitors of prostaglandin synthesis are used to facilitate closure of the ductus Arteriosus, these include indomethicin and ibuprofen in intravenous and oral formulations. Adverse drug reactions for both of these medications include reduced cerebral blood flow, oliguria, hyponatraemia and gastrointestinal complications, with indomethacin having higher rates of adverse drug events.

ParacetamolParacetamol appears to be a promising new alternative to indomethacin and ibuprofen for the closure of a PDA with possibly fewer adverse effects.

Key ObjectiveTo detect a significant patent ductus arteriosus (PDA) in infants and potentially commence treatment with paracetamol, ibuprofen, indomethacin, or surgical ligation.

Alerts If there is any concern about ductal dependant congenital heart disease, signs of

pulmonary hypertension (TR, PDA flow pattern of >30% right to left flow) PDA closure is contraindicated.

Monitor Liver Function Test (LFT) including serum bilirubin before paracetamol and at 3 days.

Monitor serum electrolytes if using ibuprofen and indomethacin. Discuss ibuprofen and indomethacin dosage with Neonatologist if urine output is

<0.5ml/kg/hr &/or Creatinine is >110micromol/L. Hyponatraemia is usually a result of fluid retention not sodium loss. This is an indication

to further reduce maintenance fluids. Ibuprofen and Indomethacin are contraindicated in infants with a platelet count <80,000 or in infants with ductal dependent congenital heart disease. Paracetamol is contraindicated in neonates with abnormal LFT’s and/or conjugated hyperbilirubinemia

Back to Table of Contents

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology2 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

CHHS18/115

Scope

This document pertains to all babies nursed in the Department of Neonatology.This document applies to staff who are working within their scope of practice: Medical Officers Registered Nurses and Registered Midwives Student under direct supervision.

Back to Table of Contents

Section 1 – When to Treat and Scan

When to treat: There are broadly 3 treatment approaches to PDA ranging from prophylactic (most

aggressive) to symptomatic treatment (least aggressive). An overview of meta-analyses evaluating different treatment approaches to close the PDA on major morbidities is presented in the table below.

Summary of meta-analyses on different approaches for treatment of PDAIVH NEC BPD Neuro-development

Prophylactic closure = = =Pre-symptomatic closure

= = = ?

Symptomatic closure = = = ?Surgical ligation = = =/

No approach has proven to be superior. Prophylactic treatment in ELBW infants reduced the incidence of IVH, but did not improve neuro-developmental outcome at 2 years of age. The few available pre-symptomatic vs symptomatic trials reduced oxygen days, but not mechanical ventilation days nor BPD. The recent DETECT trial showed that early targeted treatment in infants < 29 weeks gestation could reduce the number of infants with pulmonary haemorrhage from 23 to 9%. However, such a strategy would need the availability of a 24/7 ultrasound service. It seems that most meta-analysis of trials showed no improvement in clinical outcomes, even though PDA was reduced. It is possible that the treatment received is causing more harm than benefit or treatment is being directed at the wrong patient subgroups.

The clinical signs of PDA are not sensitive or specific. Hence echocardiography remains the mainstay for early diagnosis of PDA.

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology3 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

CHHS18/115

When to scan: Infants <28 weeks gestation: In infants <28 weeks gestation, spontaneous ductal closure is rare in the first few days of

life especially in babies with significant lung disease. Morbidities like pulmonary haemorrhage and Intraventricular haemorrhage (IVH) are also common in the first few days of life which may be pathophysiologically related to large left to right ductal shunting. In these infants pre-symptomatic echocardiogram or clinician performed ultrasound (CPU) should be considered in the first 48 hours (ideally <24 hours of age)

Treatment is recommended for large PDA’s or moderate pulsatile PDA’s (see below) with one or more signs of high shunt volume on CPU (Hemodynamically significant).

Signs of high shunt volume are: Reversed diastolic flow in descending aorta or SMA (‘ductal steal’) Increased velocities in LPA (less pulmonary artery) (LPA end diastolic velocity >0.2m/s,

LPA mean velocity >0.43m/s) Left atrial dilatation (LA:AO ratio >1.5:1) and/or ventricular dilatation Increased shunt volume: increased LVO:SVC ratio >4 or LVO: RVO ratio >1.25 Mitral regurgitation

Infants 28 weeks gestation: Infants 28 weeks gestation have a higher incidence of spontaneous ductal closure,

hence symptomatic treatment is generally recommended. An echocardiogram or CPU should be performed if there are clinical signs of a PDA (systolic murmur, wide pulse pressure, increased oxygen (O2) requirement, increasing apnoea/bradycardia, pulmonary oedema/haemorrhage).

Treatment is recommended for haemodynamically significant PDA’s as above with symptoms that are likely related to the ductal shunting including:o Inotrope resistant hypotensiono Pulmonary haemorrhageo Increased number of apnoeas over the last few dayso Persistent (>12-24 hours) increase in FiO2 (fractional inspired 02) - Increase in mean

airway pressureo Increasing respiratory distress (respiratory rate, work of breathing) not otherwise

explainedo Unable to wean off respiratory supporto The need for mechanical ventilation for which no other cause can be found

In all babies an echocardiogram or CPU should be repeated after the course of treatment has been completed to assess whether the duct has closed to aid further management.

Back to Table of Contents

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology4 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

CHHS18/115

Section 2 – PDA Size and Flow Pattern

PDA size is measured on 2D or colour flow at the site of maximum constriction. Large >2mm moderate 1.5-2mm small <1.5mm The ductal flow pattern can be classified as follows:

o Pulmonary hypertensive (bidirectional with >30% right to left shunting), o Growing (bidirectional shunt, <30% right to left shunting)o Pulsatile (left to right shunt, pulsatile flow with peak velocity approximately 1.5m/s

or <50% of maximum) o Constricting (continuous left to right flow, peak velocity >2m/s or minimum flow

velocity >50% of maximum)o Closed

Back to Table of Contents

Section 3 – Supportive Care

Respiratory support for improvements in oxygenation and lung compliance can be achieved by increasing PEEP to levels that maintain optimal recruitment. In addition this may also reduce left to right ductal flow

High daily fluid intake contributes to ductal patency. A modest fluid restriction (140-150 ml/kg/day) might help reduce the increased pulmonary fluid burden

Frusemide can stimulate prostaglandin E2 synthesis and prolong ductal patency. Hydrochlorothiazide does not increase prostaglandin E2 production and is a good alternative to treat fluid overload in preterm infants with a PDA

Special consideration should be given to feeding regimens especially if there is poor mesenteric flow or baby is severely growth restricted. Feeds should not be increased whilst on treatment medication with low threshold for discontinuation if there is feed intolerance.

Back to Table of Contents

Section 4 – Medical Treatment

Both indomethacin and ibuprofen have about a 75% success rate for ductal closure. Blood flow studies have shown that ibuprofen has less negative effects on cerebral

blood flow Oral (PO) ibuprofen has similar efficacy to intravenous (IV) ibuprofen or indomethacin Paracetamol appears to be a promising new alternative to indomethacin and ibuprofen

for the closure of a PDA with possibly fewer adverse effects IV/PO paracetamol is recommended as first line treatment for PDA closure in our unit

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology5 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

CHHS18/115

IV/PO ibuprofen will be the second line drug if paracetamol has failed or is contraindicated.

A CPU head scan is to be performed prior to treatment Refer to Neonatal Intensive Care Unit (NICU) drug manual for dosing regimen,

precautions and contraindications for each of these drugs If the PDA fails to close after a single course of paracetamol, consider second line drug. For ibuprofen and indomethacin, if the PDA fails to close after a single course of one

drug, a repeat course of same or different drug may be used (maximum 2 courses per drug) as per consultant’s discretion

Consider repeating scan after 3 days of paracetamol or loading dose of ibuprofen/indomethacin. If the PDA has closed or <1 mm in size, withholding remaining doses may be appropriate to limit side effects of medication

Observe and report any feeding intolerance and/or abdominal distension Strict fluid balance chart is essential (weigh all nappies) Daily urinalysis checking for microscopic haematuria (indication of kidney damage) Daily weigh to monitor fluid retention

Back to Table of Contents

Section 5 – Surgical Treatment

PDA ligation is associated with the adverse outcomes of an increased risk of Chronic Lung Disease (CLD) and poor neurodevelopmental outcome

PDA ligation should only be considered in select infants after 2 failed medical treatments or where medical treatment is contraindicated (Necrotising Enterocolitis [NEC], renal failure, abnormal LFT’s) with ongoing signs of cardiopulmonary compromise (cardiac failure, difficult to wean off the ventilator, difficulty tolerating feeds).

Back to Table of Contents

Implementation

This guideline will be communicated via Registrar teaching sessions and the Registrar orientation manual.

Back to Table of Contents

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology6 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

CHHS18/115

Related Policies, Procedures, Guidelines and Legislation

Policies Consent and Treatment

Procedures CHHS Patient Identification and Procedure Matching Policy

Back to Table of Contents

References

1. Kenner, C & Lott, J.W. (2007) Comprehensive Neonatal Nursing a Physiologic Perspective. W.B. Saunders. Philadelphia. 3rd Ed.

2. Evans, N. (2003). Current Controversies in the Diagnosis and Treatment of Patent Ductus Arteriosus in Preterm Infants. Advances in Neonatal Care. 3(4). 168-77.

3. Hazinski, M. (2002). Congenital Heart Disease in the Neonate Part I: Epidemiology, Cardiac Development, and Fetal Circulation. Neonatal Network. 21(3) 31 – 36.

4. Hazinski, M. (2002). Congenital Heart Disease in the Neonate Part II: Perinatal Circulatory Changes, Postnatal Circulation and Cardiovascular Physiology. Neonatal Network. 21(3).37 – 42.

5. Karlsen, Kristine & Tani, Lloyd (2003) S.T.A.B.L.E. – Cardiac Module – Recognition and stabilization of neonates with severe congenital heart disease.

6. Kenner, C. Amlung, S., Rockwern, Flandermeryer, A. & Applewhite; (2005) Protocols in Neonatal Nursing. Philadelphia, PA.; W. B Saunders Company

7. Hammerman, C., Bin-Nun, M, Markovitch, E., Schimmel, M, Kaplan, M & Fink, Dc (2011) “Ductal Closure With Paracetamol: A Surprising New Approach to Patent Ductus Arteriosus Treatment” Pediatrics 128(6) 1618-1621

8. Su B et al., (1997) Echocardiographic assessment of patent ductus arteriosus shunt flow pattern in premature infants; Archives of Diseases in Children; 77; F36-40.

9. Groves, A et al., (2006) The neonatologist as an echocardiographer NeoReviews 10. Evans, N et al., (2012) Diagnosis of the preterm patent ductus arteriosus: clinical signs,

bimarkers or ultrasound? Seminars in Perinatology, 114-122 11. Joseph B Philips. Management of patent ductus arteriosus in preterm infants.

www.uptodate.com12. John Hunter Children’s Hospital, Newcastle and Royal Prince Alfred Hospital, Sydney PDA

management guidelines

Back to Table of Contents

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology7 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register

CHHS18/115

Search Terms

PDA, Patent Ductus Arteriosus

Back to Table of Contents

Disclaimer: This document has been developed by ACT Health, Canberra Hospital and Health Services specifically for its own use. Use of this document and any reliance on the information contained therein by any third party is at his or her own risk and Health Directorate assumes no responsibility whatsoever.

Policy Team ONLY to complete the following:Date Amended Section Amended Divisional Approval Final Approval 14/03/2018 Complete Review Liz Chatham, ED WY&C CHHS Policy Committee

This document supersedes the following: Document Number Document NameCHHS13/542 Department of Neonatology - PDA Assessment and Management

Doc Number Version Issued Review Date Area Responsible PageCHHS18/115 1 19/03/2018 01/04/2022 WY&C Dept of

Neonatology8 of 8

Do not refer to a paper based copy of this policy document. The most current version can be found on the ACT Health Policy Register