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Ravi Shankar Kanithi
MD, DM PGI CHANDIGARH
Fr Professor , Niloufer Hospital
Director Sowmya Children Hospital, Hyderabad
PDA-when and how to treat?
Ravishankar Kanithi DM
Consultant Neonatologist
Sowmya Children’s Hospital
Are we entangled?
‘Treat all or treat none’ challenged
High spontaneous closure rates
lack of evidence of benefit in trials
Some subset of PDA’s will likely benefit with treatment
Identification of those babies is the key
Gestational age and PDA
ELBW <28 weeks- 20-30% spontaneous closure
Other factors which keep duct open- Intraamniotic infection, hypoxia, RDS, antenatal
steroids
Is PDA an innocent by-stander?
Adverse effects increase with each week of prolonged patency
Hazard risk for death in neonates with PDA was eight-fold than those without PDA
Adverse effects
Gestational age
Pulmonary flooding
Respiratory deterioration, CO2 retention
Pulmonary hemorrhage
BPD
Systemic steal
Circulatory instability –neonatal shock
IVH / PVL
NEC
Clinical signs of hyperdynamic circulation are usually not apparent in first 3 days
Bedside functional echocardiography
PDA- When to treat?
Early complications of PDA (IVH, pul hemorrhage) usually develop in the first 3-7 days
Clinical signs of hsPDA and heart failure develop late Efficacy of NSAID decreases with increasing PN age Evidence
Early symptomatic treatment reduces duration of ventilation and BPD Early asymptomatic treatment- decrease in incidence of later PDA, O2
requirement and PVL
PDA-TOLERATE Trial (EB Neo 2019)
Large multicenteric trial
Extreme preterm, 7-14 days, on resp support, moderate to large PDA
Randomized to treatment or no treatment
No difference
Ligation
Ped cardio follow up
mortality
Pros and cons of different treatment timings
PDA
closure
Decrease
in IVH,
Pul h’ge
Surgical
ligation
need
decreased
Unnecessary
treatment
NEC Mortality
Prophylatic (0-12 hrs) +++++ +++ +++ +++
Early Targeted (6-24 hrs) +++++ +++ +++ +
Pre/early symptomatic
(echo based <3-4 days)
+++++ ++ ++ +
Symptomatic ++ ++ ?
No treatment + +++ +++
Which PDA to treat?
Istavan seri & Martin kluckow
Comprehensive assessment of PDA
Parameter Variable Small Medium Large
PDA characteristics Ductal size (mm) <1.5 1.5-2.0 >2.0
PDA Vmax (m/s) >2.0 1.5-2.0 <1.5
Pulmonary
overcirculation
LA:Ao ratio <1.5 1.5-2.0 >2.0
LVO (ml/kg/min) <200 200-300 >300
Mitral valve E/A ratio <1 1 >1
End-diastolic LPA flow velocity (m/s)
<.3 0.3-0.5 >0.5
IVRT (ms) >40 30-40 <30
Systemic
hypoperfusion
MCA/ACA diastolic flow
forward RI ≥0.9 Absent /
reversed
Descending aortic diastolic flow
forward absent reversed
CA diastolic flow forward absent reversed
How to treat PDA?
Indomethacin
Increased risk of NEC compared with ibuprofen (Cochrane)
Less risk of IVH (TIPP Study)
Standard course- 3 doses of 0.1-0.2 mg/kg every 12-24 hrs as 30 min IV infusion
Closure rates First course-70%,
Second course- 50%
More than 2 courses PVL
Longer course (7 days) did not offer advantage over 3 days course
Concerns over oral use- effects on gastric mucosa
Ibuprofen
75% closure rates as that of indomethacin
Less adverse effects on GIT
Doubling the dose (20,10,10) achieved better result than standard dose(10,5,5) –
70% vs. 37%
Also, doubling the dose for second course-> better closure- 60% vs. 10%
Consistent evidence - oral ibuprofen achieves better closure rates than IV route
IV Ibuprofen (THAM) associated with PAH
Paracetamol
No peripheral vasoconstrictor effects
15 mg/kg 6 hrly for 2-7 days
Closure rates 70-100%, but data in extreme preterm limited
Oral equally effective
Potential long-term adverse effects on neurodevelopment- Autism, ADHD
Not FDA approved
Ligation
Primary criteria- dependence on mechanical ventilation with persistent large ductal
patency
Adverse outcomes less with delayed selective vs. early routine (<10 days) ligation
Complications – post-ligation cardiac syndrome, phrenic N injury, PX, ChX, residual
duct, accidental ligation of adjacent structures
Trans-catheter device closure
Case scenario 1
A 25 wk 750 gram male neonate
1 dose of dexamethasone was given an hour before delivery.
Baby was resuscitated with delivery room CPAP, shifted to NICU, intubated and
given surfactant 200mg/kg
At 7 hours of life - Ventilated on settings of TTV 5ml/kg, fiO2 0.3, pressures of
18/6, IT 0.4sec. Chest x ray suggestive of moderate RDS.
Should we do an echo now? Why?
Should we treat?
The baby is currently 12 hours old and was extubated and is currently on HFNC support, 6L/min (room air) , mild SCR+
Well perfused, art. BP 38/16 mm Hg (Mean 24), passed urine twice, pulses well felt
Bedside ECHO shows PDA 2.5 mm, LA/Ao 1.8
Parameter Variable Small Medium Large
PDA characteristics Ductal size (mm) <1.5 1.5-2.0 >2.0
Pulmonary
overcirculation
LA:Ao ratio <1.5 1.5-2.0 >2.0
Doppler flow patterns: (A) pulmonary hypertension pattern; (B) growing pattern; (C) pulsatile
pattern; (D) closing pattern; (E) closed pattern.
Bai-Horng Su et al. Arch Dis Child Fetal Neonatal Ed
1999;81:F197-F200
Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.
Case scenario 2
28 week 1020 gm
At CGA of 33 weeks was found on a morning round to have a murmur, no
other symptoms
Cap refill <3 s, BP 50/22 mm (Mean 34), UOP 3 ml/kg/h
Echo showed a PDA 3mm, pulsatile flow
Dilated LA &LV, LA/Ao 2.2, LVO 300 ml/kg/min
aorta – mild diastolic reversal
Case scenario 3
32 week , full course of steroids, CPAP of 5cm, FiO2 0.21
Day 3- CRT < 3 s, BP 44/18 mm (Mean 29), good vol pulses, U/O
4ml/kg/h
• ECHO – PDA 2.6 mm, LA/Ao ratio 2, aorta – normal diast flow,
MCA RI 0.6
Case 4
28 week day 1, Antenatal steroid yes, CPAP 6 cm 30%
ECHO- duct 2.5 mm, pulsatile flow, LPA end diastolic flow 0.3 m/s,
LVO 300 ml/kg /min, some reversal in descending aorta
Parameter Variable Small Medium Large
PDA characteristics Ductal size (mm) <1.5 1.5-2.0 >2.0
Pulmonary
overcirculation
End-diastolic LPA flow velocity (m/s)
<.3 0.3-0.5 >0.5
LVO (ml/kg/min) <200 200-300 >300
Systemic
hypoperfusion
Descending aortic diastolic flow
forward absent reversed
Case 5
26 week day 3 , Antenatal steroid yes, CPAP 7 cm 50 %
ECHO- duct 3.5 mm, Flow- pulsatile pattern, LPA end diastolic flow
0.5 m/s, LVO 650 0 ml/kg /min, LA:Ao ratio 2.2, Reversal in
descending aorta
Parameter Variable Small Medium Large
PDA characteristics Ductal size (mm) <1.5 1.5-2.0 >2.0
Pulmonary
overcirculation
LA:Ao ratio <1.5 1.5-2.0 >2.0
LVO (ml/kg/min) <200 200-300 >300
End-diastolic LPA flow velocity (m/s)
<.3 0.3-0.5 >0.5
Systemic
hypoperfusion
Descending aortic diastolic flow
forward absent reversed
Case 6
27 week 720 gm baby APH sudden PT delivery
ANS just 4 hrs prior to delivery
Poor apgars, delivery room CPAP later intubated for poor efforts
Shifted to NICU, First dose of surfactant given at 1 hr of age
Ventilation parameters at 6 hrs, 18/5, FiO2 60%.
PDA 2 mm
On 3rd day baby, settings were 10/4, 25% O2. HR 162/min, BP 52/28 mm
Hg.
Echo
PDA 2.5 mm, non-restrictive LR shunt
LA:Ao 1.8:1, E:A 1:1, LVO 320 ml/kg/min
Absent diastolic flow in descending aorta, ACA RI 0.9
Started on oral ibuprofen 10/5/5
Baby was extubated to CPAP on D4.
Was having intermittent apnea, brown aspirates and abdominal distention.
Sepsis work-up negative, AXR dilated loops. NEC was suspect. Feeds were
stopped on 45h day.
On 6th day HR 180/min, SSM+, chest pulsations+. Echo showed duct of 3.2
mm, LA:Ao ratio of 2:1, cranial doppler RI 0.9.
What are your treatment options now?
Pediatric cardiologist was consulted. Confirmed echo findings.
IV PCM given for 5 days
Not much clinical improvement. After 5 days ECHO findings were same.
What would you plan now?
Summary
Individualize the need for therapy based on
ANS, GA, resp support, PN age
Comprehensive ECHO assessment- duct character, pul flooding, systemic steal
When?
Babies > 28-30 weeks - symptomatic approach
Babies < 28 weeks - early targeted or pre-symptomatic approach
How?
Oral Indomethacin – if risk of IVH is high
Oral Ibuprofen (double Dose?)– in most instances
IV Paracetamol- may be tried failure cases or where oral meds cannot be given
Ligation- if vent dependent
Thank you
