Patent Ductus Arteriosus دکتر علیرضا جشنی مطلق فوق تخصص نوزادان مدیر گروه کودکان-عضو هیئت علمی دانشگاه علوم پزشکی البرز

Ductus Arteriosus(DA) The ductus arteriosus is a vascular connection found directly between the pulmonary artery and the aorta. Blood is shunted from the pulmonary artery directly into the aorta and again away from the fetal lungs Is patent in all newborns till 72 h of birth DA is held open by Increased PGI2 & PGE2 Decreased PO2 Incidence: 57/100,000

What Major Changes in Infant Circulation occur following birth? Lungs: Lungs expand PaO2↑’s Pulmonary vasodilatation Drop in pulmonary vascular resistance. Systemic Circulation: Resistance ↑’s with placental removal PDA: flow reverses to L R shunting Begins to functionally close due to ↑ PaO2, and decreased PGE2 levels

What Physical Exam findings are consistent with PDA? Cardiac: Active Precordium, Widened Pulse Pressure, Bounding Pulses Murmur: systolic at LUSB/Left Infraclavicular, may progress to continuous (machinery) Widened pulse pressure that is greater than 25 mmHg or if the difference between the systolic and diastolic blood pressure (BP) exceeds half of the value of the systolic BP Respiratory Sx: Tachypnea, Apnea, CO2, increased vent settings

What further diagnostic studies could be done to confirm this? CXR Echocardiogram

What findings on this CXR are suggestive of a PDA? Increased Pulmonary vascular makings Cardiomegaly Uptodate.com

Echocardiogram Gold standard for diagnosing PDA Taken from Neo Reviews

Which Infants are at greatest risk? The Youngest: risk increases with decreasing gestational age The Smallest: 80% of ELBW infants (BW <1000g) with a murmur progress to large persistent PDAs

What are complications of having hemodynamically significant PDA? Pulmonary Edema Pulmonary Hemorrhage BPD Heart Failure Pulmonary haemorrhage CLD

What are complications of having hemodynamically significant PDA? IVH NEC Prolonged ventilator/O2 support Longer Duration of hospitalization. IVH NEC

What makes a PDA Hemodynamically Significant? Pulmonary Overcirculation (↑ Qp) Systemic Hypoperfusion (↓ Qs) Oxygenation failure Increased Vent Requirements Pulmonary Edema Cardiomegaly Systemic Hypotension End-Organ Hypoperfusion Renal Insufficiency NEC IVH Acidosis (metabolic, lactic)

Pedea:

TREATING? Lower death, need for rescue treatment and patient drop-out (Aranda 2009) Lower mortality rate after PDA closure (Noori 2009) Lower incidence of NEC (Cassady 1989) Failure to close PDA is a risk factor for CLD (Adrouche-Amrani 2012)

Management of PDA: Ibuprofen or Indometacin Surgery (if DA fails to close after two course of medical management or reopen ) Cardiac catheterization

ibuprofen IS THE GOLDEN STANDARD TO ESCAPE FROM:

ibuprofen: Indication: treatment of significant patent ductus arterious in preterm newborn infants less than 34 weeks GA but is less efficient in preterms less than 27 weeks Dosage form: 5mg/ml ibuprofen IV solution , 2 ml amp

Treatment regimen The dose is adjusted to the body weight as follows: 1st injection:10mg/kg 2nd injection :5 mg/kg 3rd injection: 5 mg/kg Second course : 48 hours after the last injection 5 5 10 5 10 5

Drug usage advisement Intravenous infusion with an infusion pump without dilution during 15 minutes

Contraindication Life threatening infection Thrombocytopenia or Coagulation defect Hepatic or Renal disorders Cyanotic Heart Disease that is duct dependent(PA,TOF,…) Suspect or Definite NEC Hypersensitivity to iboprufen

Complications

Clinical study

WHY ORAL IS NOT A GOOD OPTION 2x More NEC with enteral Ibu (Gouyon 2010) Additionnal risk due to hyperosmolarity in enteral formulations (Perera-da-Silva 2008) Transient but sever acute renal failure (Erdeve 2008) Oral trials are underpowered to detect complications (Jobe 2011) Higher dose needed to close PDA with enteral ibu than IV (Sharma 2003) EMA/FDA approved not oral = off label Higher reopening rates with Oral and safety underpowered (Erdeve et al 2011)

Summary Ready to use formula intravenous ibuprofen EMEA approved Good safety profile vs Surgery Preferred drug in many reviews(cochrane golden standard) High dose vs Standard dose