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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) Respiratory Sx: Tachypnea, Apnea, CO2, increased vent 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 Uptodate.com Cardiomegaly 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) Oxygenation failure Increased Vent Requirements Pulmonary Edema Cardiomegaly Systemic Hypoperfusion (↓ Qs) 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 10 10 5 5 5 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 Oral 2011) but sever acute renal failure (Erdeve 2008) trials are underpowered to detect complications (Jobe Higher dose needed to close PDA with enteral ibu than IV (Sharma 2003) EMA/FDA Higher approved not oral = off label 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