Cardiovascular Section

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Contents

1.0 Aim of guideline
2.0 Scope of guideline
3.0 Guideline
Appendix 1 – Echocardiographic and clinical scoring
Appendix 2 – PDA Ligation Referral Pathway
Appendix 3 – PDA Ligation Referral Pathway – Guidance Notes
Appendix 4 – PDA Ligation Referral Form
Appendix 5 – PDA Parent Information Leaflet
Appendix 6 – Paracetamol administration details, PDA closure, monitoring and further information
Appendix 7 – Ibuprofen administration details, monitoring, further information and repeated course

1.0 Aim of guideline

A guideline framework to support clinicians in the management of Patent Ductus Arteriosus (PDA) in neonates within neonatal services within TV & Wessex Neonatal ODN. Medical management is only indicated in the presence of one or more definite clinical symptoms and ECHO evidence of haemodynamically significant PDA.

2.0 Scope of guideline

This guideline applies to all neonatal Units within the TV & Wessex Neonatal ODN.  This includes the following hospitals.

3.0 Guideline

Background, treatment options and definition of ‘symptomatic’ treatment

There is a wide variation in the rate of spontaneous ductal closure in preterm babies. A persistently patent duct with a large ductal shunt can lead to increased pulmonary perfusion, as well as decreased systemic blood flow (and/or end-organ perfusion); and has been associated with increased mortality and numerous preterm morbidities (fluctuations in BP and resultant IVH, pulmonary haemorrhage, ventilator dependence, CLD and NEC).

Pharmacologic treatment with COX-inhibitors, cyclo-oxygenase inhibitors (ie indomethacin, ibuprofen) and paracetamol) can be prophylactic, ‘pre-symptomatic’ (before the evolution of symptoms of ductal shunt) or ‘symptomatic’ (treatment is delayed until the presence of clinical symptoms). Prophylactic treatment with indomethacin or ibuprofen hasn’t been associated with increased survival or better long-term outcome. There is not enough evidence at present to recommend prophylactic paracetamol administration. Recent results from RCTs comparing echo screening and early pharmacologic treatment in asymptomatic babies versus delaying treatment until well-defined clinical symptoms of high-volume ductal shunt were met demonstrated no benefit (or very little benefit (TRIOCAPI)) of echo screening.

In view of these results, routine echo screening and pharmacologic treatment in preterm infants without clinical symptoms are not indicated. Preterm and IUGR infants below 32 weeks with clinical symptoms (as below) should undergo diagnostic echocardiography and receive treatment if needed.  Scoring systems for clinical symptoms and echo findings of haemodynamic significance have been introduced recently to aid decision-making. An example is shown in Appendix 1.

Clinical symptoms suggestive of high-volume ductal shunt:

Echo features of haemodynamic significance. Initial assessment should include establishment of normal structure (complete sequential segmental analysis). If baby doesn’t tolerate study, please measure PDA size, flow pattern, LA:Ao, LPA end-diastolic flow velocity and flow pattern in descending aorta.

Conservative management:

Fluid restriction Consider fluid restriction (not below 120 ml/kg/day) and diuretic therapy. Chlorothiazide and spironolactone are preferred over furosemide if enteral intake is more than 50% of total intake.  Once full enteral feeding has been established, fluid intake can be increased in order to reach adequate energy and protein intake with the concurrent administration of diuretics.

PEEP Consider increasing PEEP by 1-2 cm H2O if ventilated or on nCPAP. No data on nHFT.

Correct anaemia Keep Hb > 12 g/L in ventilated preterm infants with significant PDA. Transfuse with co-administration of diuretics ie Furosemide.

Pharmacological treatment:

Pharmacological treatment is only indicated in babies with PDA-related clinical symptoms and echo-confirmed haemodynamically significant PDA. Use of COX-inhibitor in asymptomatic babies is not indicated, unless very significant echo findings. Scoring systems for clinical and echo findings can aid decision-making. An example is shown in Appendix 1.

Ibuprofen or Paracetamol

Recent meta-analyses suggest that the efficacy of Paracetamol and Ibuprofen is very similar, but Paracetamol has a more favourable side effect profile (less NEC, GI bleeding and renal impairment). Most studies included very preterm babies (GA < 32 weeks) and there is a relative paucity of data regarding the more preterm population (GA < 28 weeks). Well-designed studies in babies GA < 28 weeks are pending. It is difficult to make firm recommendation at present which drug should be used as routine first-line.

High-dose Ibuprofen (beyond day 7) has been reported to be more effective than standard dose. Oral administration is more effective for both drugs.

Use standard dose Ibuprofen 3 day course: 10mg/kg/OD on day 1 followed by 5mg/kg/OD on days 2 and 3 at 24 hourly intervals or Paracetamol (15 mg/kg, QDS, for 3 days) as routine pharmacological treatment.

Use oral preparations (rather than IV) if baby is receiving >100 ml/kg enteral feeds; the use of oral preparations can be considered with smaller enteral volumes (senior clinician choice) Re-assess the ductus arteriosus and ductal shunt after 3 days;

A second course or course extension to 6 days of high dose Ibuprofen (3 day course: 10mg/kg/OD on day 1 followed by 5mg/kg/OD on days 2 and 3) or same dose Paracetamol can be considered, if necessary. A third course of the alternate drug might be considered, but literature data about the efficacy of a third course is scarce.

Contraindications

Ibuprofen Life-threatening infection; active bleeding; thrombocytopenia (platelets <50); coagulation defects; significant renal impairment; known/suspected NEC; pulmonary hypertension; duct-dependent circulation, recent IVH (within 24 hours).

Side effects GI perforation (consider Ibuprofen carefully in IUGR and after hydrocortisone administration due to pressor-resistant hypotension); increased serum creatinine; hyponatraemia; oliguria; fluid retention; acute renal failure, platelet dysfunction and thrombocytopenia; neutropenia; haematuria; pulmonary haemorrhage; IVH; PVL. Less common: GI haemorrhage; hypoxaemia.

Monitor/Caution Watch for signs of bleeding; may mask symptoms of infection; monitor renal function. Ibuprofen may decrease clearance of aminoglycosides so strict surveillance of serum levels is recommended. In cases of oliguria or rising creatinine, doses of aminoglycosides should be held until levels are available. Ibuprofen interferes with bilirubin-albumin binding increasing unbound bilirubin and should not be used in infants with hyperbilirubinaemia approaching exchange transfusion levels.

Paracetamol Use Paracetamol if there are contraindications to Ibuprofen. Overdose can cause liver toxicity. Check liver function before each course and at least once during the course.

Ligation:

PDA ligation should not be the primary treatment of choice and should be preceded by pharmacological treatment where possible. Ligation is generally not recommended in the first 3 weeks of life. If multiple courses of medical treatment have failed to close or restrict a haemodynamically significant duct and echo assessment confirms a high-volume shunt in a symptomatic patient refer for a paediatric cardiology opinion. If respiratory problems are predominant consideration of steroids and diuretics should be given prior to PDA ligation.

Ligation is only indicated when a) the PDA echo score is high (haemodynamically significant duct on echo) and b) there is no other explanation for persistent clinical symptoms such as:

• Increasing ventilatory requirement over several days (FiO₂ > 40-50%, MAP >12-13 cmH₂O) with signs of pulmonary hyperaemia on the CXR or ventilator dependence and unable to extubate.
• Hypotension requiring inotropic support.
• Oliguria/renal failure.

Transcatheter PDA closure

Although transcatheter closure of PDA is common practice in older infants and children, it is still a relatively new approach in preterm infants. In this method, a device is used to plug the PDA via a transcatheter approach through the femoral vein. The data although limited is encouraging. However more studies are needed for analysing long term and short-term outcomes compared to surgical ligation.

In selected cases of preterm infants of reasonable size (body weight approximately 2 kg and more), this option for PDA closure could be considered with the cardiology team. This should include a clear plan around transport to the theatres, temperature management and support in the theatre and the logistics of the post-operative recovery period.

Appendix 1.

Echocardiographic and clinical scoring (adapted from Brigham’s Neonatal Unit, Boston, MA guideline)

Please click on the link below to calculate the PDA score on the adapted PDA SCAMP tool

https://neogrow.shinyapps.io/pdascamp/

Appendix 2.

PDA Ligation Referral Pathway (from TVW Neonatal ODN Cardiac Care Pathway v1.3)

Appendix 3.

PDA Ligation Referral Pathway – Guidance Notes

Appendix 4.

PDA Ligation Referral Form

Appendix 5.

PDA Parent Information Leaflet

Appendix 6.

Paracetamol administration details, PDA closure, monitoring and further information

Appendix 7.

Ibuprofen administration details, monitoring, further information and repeated course

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