Ductus Arteriosus

1,702 views
1,507 views

Published on

International conference «Actual approaches to the extremely preterm babies: International experience and Ukrainian realities» (Kyiv, Ukraine, March 5-6, 2013)

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,702
On SlideShare
0
From Embeds
0
Number of Embeds
47
Actions
Shares
0
Downloads
80
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

Ductus Arteriosus

  1. 1. Ductus Arteriosus Kyiv March 2013 Jan Širc Institute for the Care of Mother and Child, Prague, Czech Republic Third Faculty of Medicine, Charles University, Prague, Czech RepublicThe HIP Trial is funded by the European Commission within the 7th Framework Programme
  2. 2. Patent ductus arteriosus The HIP Trial is funded by the European Commission within the 7th Framework Programme
  3. 3. Ductus arteriosus – spontaneous closure1. stage. Blood entering the ductus and its vasa vasorum from the aorta has a high Po2 after delivery, which, along with alterations in prostaglandin metabolism, leads to constriction and closure of the ductus arteriosus.2. stage. A second stage of closure related to fibrous proliferation of the intima is complete in 2-3 weeks. Patency after 3 months is considered abnormal. The HIP Trial is funded by the European Commission within the 7th Framework Programme
  4. 4. Ductus arteriosus – spontaneous closure• Spontaneous closure during 96 hrs in term infants• VLBW between day 3 and 7 – 44% below 32 weeks of gestation (Van Overmeire et al. J Pediatr 2001; 138; 205-211)• VLBW Day 8 – 34% in ELBW infants (Koch et al. Pediatrics 2006; 117; 1113-1121)• 24% in 23-27 weeks of gestation - (Dani et al. Acta Paediatr 2008; 97; 1176-1180)• Spontaneous closure in 100% of very low birth weight infants up to 1 year - Herman et al. Arch Dis Child Fetal Neonatal Ed 2009• 96% of VLBW up to 18 months - Kucera, Sirc, Semberova, Stranak 2011 The HIP Trial is funded by the European Commission within the 7th Framework Programme
  5. 5. Ductus arteriosus – spontaneous closureVLBW PDA % 100 90 80 70 60 50 40 PDA % 30 20 10 0 Day Day Day Day Day Day Day Day Day Day 7 14 21 28 35 42 49 56 63 70 Letshwiti et al. Irish & American Paediatic Society Meeting 2010 DublinThe HIP Trial is funded by the European Commission within the 7th Framework Programme
  6. 6. PDA - diagnosis • Early 1. Clinical - mostly silent, with no murmur. BP may be low (systolic, diastolic and mean) with normal pulse pressure 2. Biochemical – influenced by clinical condition during transitional period 3. Echocardiographical • Late 1. Clinical – murmur, hypotension, increased pulses, wide pulse pressure, Respiratory deterioration, congestive heart failure 2. Biochemical - BNP, pro-BNP, NT-proBNP, Troponin T – cTnT, metabolic acidosis, lactate 3. Echocardiographical The HIP Trial is funded by the European Commission within the 7th Framework Programme
  7. 7. PDA – clinical/echo diagnosis Week 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th (patients) week week week week week week week week week week PDA clinical assessment 80 75 92 67 56 57 57 43 33 50 vs. ECHO (% correct dg.) Letshwiti et al. Irish & American Paediatic Society Meeting 2010 Dublin The HIP Trial is funded by the European Commission within the 7th Framework Programme
  8. 8. PDA - diagnosis• Echocardiogram is required for early diagnosis of PDA in preterm infants, as clinical signs are not reliable in the first few days of life – (Alagarsamy S et al. J Perinat Med. 2005;33(2):161-4.) The HIP Trial is funded by the European Commission within the 7th Framework Programme
  9. 9. PDA stagingMcNamara et al. Arch Dis Child Fetal Neonatal Ed. 2007 Nov;92(6):F424-7 The HIP Trial is funded by the European Commission within the 7th Framework Programme
  10. 10. Echocardiography - components1. Ductal size2. Direction and pattern of ductal flow3. Left atrial and ventricular size, Left atrium to aorta ratio (LA:Ao ratio)4. Flow in main pulmonary artery (MPA)5. Diastolic flow in pulmonary arteries6. Diastolic flow in abdominal aorta7. Patency of foramen ovale (FOA) The HIP Trial is funded by the European Commission within the 7th Framework Programme
  11. 11. Ductal size• Combine cross-sectional 2D image with colour Doppler• Short-axis view - three-legged stool is usually seen• Ductal constriction begins at the pulmonary end or in the middle• Measure internal diameter of narrowest part• Measurement from colour Doppler – appropriate gain ! Size – preterms Small < 1.5 mm Medium 1.5 – 2.0 mm Large > 2 mm The HIP Trial is funded by the European Commission within the 7th Framework Programme
  12. 12. Direction and pattern of ductal flow• By pulsed and/or CW Doppler• Bidirectional flow – first 48 hrs, PPHN• Small, restricted PDA – high velocity in both systole and diastole ( > 1 m/s)• Large PDA – lower velocity in systole, very low flow in diastole (almost zero) The HIP Trial is funded by the European Commission within the 7th Framework Programme
  13. 13. Left atrial and ventricular size• Most often used left atrium to aorta ratio (LA:Ao ratio)• Long axis view• Poor specificity and sensitivity – affected by LV dysfunction, hydratation, atrial shunting• Not reliable in the first 24-48 hours of life LA:Ao ratio Small PDA < 1.4:1 Moderate 1.4:1 – 1.6 Large PDA > 1.6 The HIP Trial is funded by the European Commission within the 7th Framework Programme
  14. 14. Flow in main pulmonary artery (MPA)• Suprasternal short axis view/adjusted parasternal view• Colour Doppler small PDA – narrow jet, does not reach pulmonary valve moderate – wider jet to the pulmonary valve large PDA – very wide jet reaches valve and swirls back• Pulsed and/or CW Doppler small PDA – flow curve is surrounded, no flow in diastole large PDA – „hairy“ curve with diastolic flow The HIP Trial is funded by the European Commission within the 7th Framework Programme
  15. 15. Diastolic flow in pulmonary arteries• Short axis view - three-legged stool• Left pulmonary artery is mostly used• End-diastolic antegrade flow PDA size flow Small > 20-30 cm/s Moderate 30-50 cm/s Large > 50 cm/s The HIP Trial is funded by the European Commission within the 7th Framework Programme
  16. 16. Diastolic flow in abdominal aorta• Subcostal view in the middle of aorta at the level of diaphragm• Restrictive flow or „steal“ phenomena when PDA is significant The HIP Trial is funded by the European Commission within the 7th Framework Programme
  17. 17. Patency of foramen ovale (FOA)• Foramen ovale decompress left atrium and ventricle• Decreases LA/Ao The HIP Trial is funded by the European Commission within the 7th Framework Programme
  18. 18. Diagnosis – X-ray• Nonspecific• Cardiomegaly• Pulmonary edema• Horizontal position of left pulmonary artery The HIP Trial is funded by the European Commission within the 7th Framework Programme
  19. 19. Biochemical diagnosis• Specific markers of heart overload: pro-BNP, BNP, NT-proBNP Troponin T, I – cTnT, cTnI Pre-prohormone• Metabolic acidosis (134 AA)• Elevated lactate ProBNP (108 AA) BNP NTproBNP (32 AA, t ½ = 20 min) (inactiv, t ½ = 60 min) The HIP Trial is funded by the European Commission within the 7th Framework Programme
  20. 20. Brain natriuretic peptide (BNP)• Secreted from ventricular and atrial myocytes during pressure and volume overload• Renin-angiotensin antagonist - diuretic, natriuretic and vasodilatation effects ↓ intravascular volume ↓ preload ↓ afterloadNeonates• Corelation with left-to-right shunting and systolic pressure of RV• Negative correlation with LV ejection fraction• Increases after birth, reaches maximal levels 3-4 days after the birth, then decreases The HIP Trial is funded by the European Commission within the 7th Framework Programme
  21. 21. cTnT• Increases 2 hrs after insult, max levels at 12 hrs• No corelation with gestation age or ECHO parameters of myocardial dysfunction• Significantly ↑ in RDS and RDS+inotropic support (0.15 resp. 0.3 ug/l)• Marker of hemodynamicaly significant PDA (hsPDA) with poor outcome Normal values Term infants < 0.05 ug/l Preterm 0.15 – 0.3 ug/l The HIP Trial is funded by the European Commission within the 7th Framework Programme
  22. 22. NTproBNP, TNT and outcome• 80 infants below 32 gt, BW 1060 g• NTproBNP and Troponin T at 48 hrs of life p < 0,001 p < 0,001PDA 0 PDA+ PDA+PIVH III/IV, †LA/Ao ratio, flow in abdominal aorta, PDA diameter did not change El-Khuffash et al, Arch Dis Fetal Neonatal Ed 2008,93:407-412 The HIP Trial is funded by the European Commission within the 7th Framework Programme
  23. 23. PDA treatment1. Prevention - noninvasive ventilation, avoid of infection, stable circulation, fluid management, normoxemia, permisive hypercapnia, minimal correction of metabolic acidosis2. Conservative approach – fluid restriction, diuretics3. Pharmacotherapy a) profylactic – first 24 hrs b) early presymptomatic c) late symptomatic• Reduction of PG synthesis by inhibition of cyclooxygenase (COX) produces constriction of the ductus. The HIP Trial is funded by the European Commission within the 7th Framework Programme
  24. 24. PDA treatmentPharmacotherapy• Indomethacin• Ibuprofen – Ibuprofen therapy on the third day of life is as efficacious as indomethacin for the treatment of patent ductus arteriosus in preterm infants with the respiratory distress syndrome and is significantly less likely to induce oliguria (Van Overmeire et al N Engl J Med. 2000 Sep 7;343(10):674-81.)4. Surgical ligation The HIP Trial is funded by the European Commission within the 7th Framework Programme
  25. 25. PDA treatment – should we do it?Subsequent studies confirmed the association of PDA with• Pulmonary haemorrhage• Severe RDS• CLD/BPD• NEC• Renal impairment• IVH• PVL• Cerebral palsy• Death The HIP Trial is funded by the European Commission within the 7th Framework Programme
  26. 26. PDA treatment – should we do it?Cochrane reviews• Prophylactic indomethacin decreasing IVH, however no impact on neurodevelopmental outcome• Indo/Ibuprofen treatment – higher closure rate, but not any meaningful short term or long term benefit• Prophylactic ligation decreasing NEC stage II and III, however exposing large number of infant to very invasive therapy (with unknown long term outcomes)Peter W Fowlie, Peter G Davis, William McGuire, 2010TIPP study (2001) – 1202 infants; 2872 infants in all trialsLucy Cooke, Peter A Steer, Paul G Woodgate, 2009Arne Ohlsson, Sachin S Shah, 2009Arne Ohlsson, Rajneesh Walia, Sachin S Shah, 2010Rafat Mosalli, Khalid AlFaleh, 2010Manoj N Malviya, Arne Ohlsson, Sachin S Shah, 2008 The HIP Trial is funded by the European Commission within the 7th Framework Programme
  27. 27. PDA treatment – should we do it?• Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis? Benitz WE Journal of Perinatology, 2010; 30:241• Meta – Analysis• 49 trials, 4728 subjects• Objective to ascertain whether there is any evidence, however weak, to support prophylaxis or treatmentConclusion• The data do not permit to reject null hypothesis• Early treatment of PDA does not improve outcomes in preterm infants The HIP Trial is funded by the European Commission within the 7th Framework Programme
  28. 28. PDA treatment - Conclusions• Ligation, indomethacine and ibuprofen are effective for achieving ductal closure• Prophylactic indomethacine reduces incidence of IVH without improvement of neurodevelopmental outcomes• There is no evidence for improvement in the incidence of death, BPD, NEC or other morbidity with PDA treatment• More conservative approach to management of PDA seems to be feasible• Routine use of COX inhibitors or surgery to achieve early ductal closure is no longer recommended• ? Early targeted treatment with use of echocardiography (identifications of infants in the risk - if there is causal linkage of PDA to adverse outcomes)• ? Late treatment using strict echocardiographic/clinical signs of cardiovascular compromise (staging) The HIP Trial is funded by the European Commission within the 7th Framework Programme
  29. 29. Thanks a lot for your attentionThe HIP Trial is funded by the European Commission within the 7th Framework Programme

×