Targeted Management of PDA in Preterm Infants

Dr. Abdulla Al TuhamiConsultant Pediatrics & Neonatology

• Still controversy • Pathological or non pathological• Causality or co occurrence

PDA with high volume shunt

Chronic lung changes NEC

First 72 hours Evidence

First 5 days

After 5 days

Long term

Evidence

Less Evidence

No Evidence

Pulmonary Hemorrhage

Neurodevelopmental

IVH

Therapeutic strategies for a PDA in extremely preterm infants

Prophylactic treatment

Symptomatic treatment

Early targeted

treatment

Following MENT Trial

1994

Increase of use indo

Following TIPP Trial

2001

Decline of use of indo

Prophylactic treatment approach

Within 24 hr of age in ELBW

May reduce the rates of PDA, PDA ligation, severe IVH, and pulmonary hemorrhage (multicenter controlled trial-Ment-trial)*

May reduce BPD and BPD or death **

*Pediatrics , 1994;93:543e50**J Pediatr 2017;187:119e26

Prophylactic treatment approach

Unnecessary treatment

No evidence of benefits on long-term neurodevelopmental outcome (TIPP trial )

*Schemedit B et al : N Engl J Med 2001;344

.

Prophylactic treatment approach

Prophylactic treatment approach

The available evidence does not support a routine universal prophylactic approach

A reasonable choice for ELBW in NICUs where IVH and PDA are frequent problems

J.pedneo.2019.10.002

.

Symptomatic treatment approach

Select populations vulnerable to hsPDA

Serial echo daily Echocardiographic

parameters of hsPDA

Treatment

Early targeted treatment approach

BiomarkersNIRS

A)POPULATIONS VULNERABLE TO hsPDA

• Clinical factors• Risk Category based on –GA • Risk of organ injury –based on

chronologic age

Early targeted treatment approach

A ) Vulnerable population

Early targeted treatment approach

J Perinat Med 2005;33:161-164

Arch Dis Child Fetal Neonatal Ed 1997;77:F36e40

precede clinical signs by ~1.8 days

NO standard definition of

hsPDA

Low sensitivity /high specificity

• False negative results

Echocardiography has become essential in the evaluation ofclinically significant ductal shunting

B) Echocardiographic parameters of hsPDA

APDA DIAMETER

BPulmonary over-circulation

CSystemic hypo-perfusion

Moderate PDA

1.5-3.0 mmor PDA:LPA= 0.5-1

Vmax <2 m/s

At least 2 of the following:

-LA: Ao 1.5-2.0- IVRT 45-55 ms- E:A 1.0- LVO 300-400 mL/kg/min

Absent diastolic flow in at least 2 of the following:

- Abdominal aorta- Celiac trunk- Middle cerebral artery

large PDA

>3.0 mm

or PDA: LPA >1

Vmax <2 m/s

At least 2 of the following:-LPA EDV more than 0.2 m/sec - LA: Ao >2.0- IVRT <45 ms- E:A >1.0- LVO >400 mL/kg/min

Reversed diastolic flow in at least 2 of the following:

- Abdominal aorta- Celiac trunk- Middle cerebral artery

B) Echocardiographic parameters of hsPDA

LA/Ao ratioLA/Ao ratio >1.5 beyond DOL 1

Correlates significantly with increased PDA flow

Sensitivity Specificity

79% D188% after D1

95%

ArchDisChild1994;70:F112-F117

LA/Ao ratio use in 1st day is not recommended

Ductal diameter >2.0 mm

Ductal flow

pattern (growing, pulsatile )

Simultaneously Using a ductal diameter >2.0 mm and the ductal flow pattern (growing, pulsatile ) may further enhance the clinical predictive capacity of ECHO

• The best markers of hemodynamic significance :

• color Doppler diameter ≥2mm

• absent or retrograde diastolic flow in the post-ductal aorta

Evans NJ, Iyer P. Journal of Pediatrics 1994;125:778-785.

Therapeutic modalities for PDA in extremely preterm infants

Conservative management

Pharmacological treatment

Surgical ligationCatheterization

closure

How to treat ?

Conservative managementShunt modulating strategy

Fluid restriction ?? Evidence

Optimal saturation

Maintain adequate PEEP

Maintain the hemoglobin above 110 g/L

Indomethacin

used for prophylactic or symptomatic treatment

Prophylactic indomethacin for IVH beginning within 24 h of birth may reduce IVH, early severe pulmonary hemorrhage and PDA ligation

Indomethacin

Adverse effects include hyponatremia, oliguria, active bleeding, and transient impaired renal function

Simultaneous administration of indomethacin and steroids has been shown to increase the incidence of gastrointestinal perforations/NEC

Ibuprofen

Intravenous ibuprofen is as effective as indomethacin in closing PDA

may reduce the risk of NEC and transient renal insufficiency

Oral ibuprofen as effective as intravenous ibuprofen

Paracetamol

Paracetamol appears to be an alternative to indomethacin and ibuprofen

possibly fewer adverse effects

Transient increase in liver enzymes

Association with Autism ???

There is insufficient evidence to recommend paracetamol as standard treatment

Echocardiography guided approach has the potential to reduce the number of drug doses*

Follow up NPE after treatment (PA branch stenosis /CoA )**

A second course If there are no contraindications or side effects from a first course

*Carmo K , Evans .N , J Pediatrics 2009**Bravo et al , J Matern. Fetal Neonatal Med , 2014David Van et al , Pediatric Research 2018