Presentation on theme: "Patent Ductus Arteriosus in the Preterm Infant (PDA)"— Presentation transcript:
1 Patent Ductus Arteriosus in the Preterm Infant (PDA) Clinical dilemmaBurnard ED. The cardiac murmur in relation to symptoms in the newborn. Br Med J. 1939;1:134Rudolph AM, Drorbaugh JE, Auld PAM, et al. Studies on the circulation in the neonatal period. Pediatrics. 1961;27: 551–556
5 Functional closureFetal circulation & PDA Patency (PGE2, No )After BirthINCREASE PaO2 , Cytochrome-P450, inhibits K+)Pulmonary Vascular resistanceCirculating PGE2 and Its receptors Bouayad et al, am J physiol Heart Circ 380:2001Antenatal Steroid Am J Physiol Heart Circ Physiol, Sep 1981; 241: H415 - H420Vitamin AWu GR et al, pediat res 49,: ; 2001 ,
6 Anatomical closure & Remodeling Constrictive effect of O2Loss of responsiveness to PGE2Obliteration of vessel lumenReduction in intramural vasa vasorum blood flowDuctus wall hypoxia lead to reduction PGE2 and NO production (Apoptosis VEGF)Preterm infant fail in this remodeling mechanismKajino et al, Factors that increase the contractile tone of DA Am j physiol 281 ;2001
7 Patency of the preterm fetal ductus arteriosus The preterm DA is morphologically and biochemically immature Edward M 2007Poorly responsive to contractile stimuliLow oxygen tensionVasodilators ( adenosine, PGE, NO )The excessive inhibitory effects of endogenous PGE and NO + a weaker intrinsic DA toneWith increasing ductal dependency on NO inhibition of prostaglandin production woul;d become less likely to produce ductal constrictionAm J Physiol 287: R652–R660, 2004.
9 Spontaneous permanent closure of the DA in ELBW neonates Koch, J. et al. Pediatrics 2006;117:
10 The cumulative permanent closure rate of the DA by serial ECHO in 42 ELBW neonates during the first 10 days postnatallyKoch, J. et al. Pediatrics 2006;117:
11 Incidence of PDA in different GA At AFHSR 2006-2007 35/14029/24437/1183
12 The usual story PRETERM MALE INFANT WITH HMD Treated with mechanical ventilation, and SURFACTANTImproved, with lower inspired oxygen requirements and ventilation supportAminophyline started in preparing for extubation2-3 days, when discussions ensued about EXTUBATIONFiO2 requirement and pressure support increased
13 Hemodynamic alteration Magnitude of L R shunt ( >50% COP)Increase pulmonary venous pressure and Pulmonary congestionIncreaser HR and stroke volumeBlood flow rearrangement lead to organ hypoperfusionPulmonary hemorrhagePediatr Res 35:331A, 1994
16 Course Left-to-right shunting through the ductus. Increased pulmonary blood flow & pulmonary congestionHemorrhagic pulmonary EdemaWorsening respiratory status with ventilation difficulties surfactant dysfunctionReduced organ perfusionMetabolic AcidosisPDA affects key outcome variables of early preterm life.Lung Biology in health and Disease vol84.,p ,1995
17 Clinical Diagnosis Failure to wean ventilator pressures and O2 Systolic murmur at the left upper sternal edge radiating to the backIncreased precardial impulsesWidened pulse pressureProminent or bounding peripheral pulsesJ Paediatr Child Health. 1994;30:406–411
18 How good is clinical examination at detecting a significant patent ductus arteriosus in preterm neonate ?
19 Is It diagnostic ? Homodynamic significance PDA Very low sensitivity for diagnosisMost significant PDA did not produce clinical signs.Davis P . Arch Pediatr Adolesc Med. 1995;149:1136–1141
21 CLINICAL BOTTOM LINEClinical evaluation of PDA, either by auscultation or by palpation of pulses, is of limited valueReliance on clinical signs results in a delayed diagnosis of PDA.Doppler flow echocardiography is required to confidently rule in or rule out the diagnosis of PDA.J Perinat Med. 2005;33(2):161-4.
22 Do I need to confirm ? No pediatric cardiologist ! What I will do ? PDADo I need to confirm ?No pediatric cardiologist !What I will do ?
23 Echocardiographic Diagnosis The consequence is accurate but rarely timely diagnosisAvailability of Pediatric cardiologist & ECHODoes this baby have a structurally normal heart?Requires neonatologists to develop the skills to perform the imaging.NeoReviews Vol.5 No.3 March 2004
24 ECHO Anatomy of the Great Vessels Is the Ductus Arteriosus Patent? Direct Imaging OF DATURBULENCE IN THE MPAIs the Ductal Shunting Hemodynamically Significant?VOLUME OF DUCTAL SHUNTING (Qp:Qs)
25 Echocardiographic tracing with pulsed Doppler of normal pulmonary artery flow, showing systolic forward flow and minimal turbulence in diastole.
27 Echocardiographic tracing with pulsed Doppler of bidirectional shunting that can occur as right-sided pressures of the duct increase (before exceeding systemic pressures).
28 Case 1 PRETERM MALE INFANT WITH HMD Treated with mechanical ventilation, and SURFACTANTImproved, with lower inspired oxygen requirements and ventilation supportAminophyline started in preparing for extubation2-3 days, when discussions ensued about EXTUBATIONFiO2 requirement and pressure support increased
29 Case 2 Female, Preterm infant 850gm HMD, Received one dose of surfactantExtubated To nasal CPAP with FiO after aminophylin loading and maintainedN. Gastric Feeding initiatedThird day a loud systolic murmur heard with widing pulse pressureABG Norma, maintain normal hemodynamic status
30 Do I confirm The diagnosis? PDADo I confirm The diagnosis?Shall I treat?Which one I will treat?How I will treat?
31 Conservative treatment for patent ductus arteriosus in the preterm It is important to make distinguish between a clinically significant and non-significant PDAFluid restriction (maximum 130 ml/kg a day beyond day 3Adjustment of ventilation by lowering inspiratory time to as low as 0.35 s, and giving higher PEEPArch Dis Child Fetal Neonatal Ed 2007;92:F244–F247.
32 Occurrence of patent ductus arteriosus (PDA) in 109 conservatively managed preterm neonates (30 weeks’ gestation, requiring ventilation and surfactant treatment (retrospective analysis).Arch. Dis. Child. Fetal Neonatal Ed. 2007;92; ;
36 Impact of patent ductus arteriosus cerebral oxygenation in preterm infants. A hemodynamically significant patent ductus arteriosus has a negative effect on cerebral oxygenation in the premature infant.Subsequent and adequate treatment of a PDA may prevent diminished cerebral perfusion and reduces the change of damage to the vulnerable immature brain.PEDIATRICS Vol. 121 No. 1 January 2008, pp
37 Markers may identify preterm with PDA at high risk It is difficult to predict which infants with a PDA go on to develop major complicationsConventional echocardiographic markers applied at 48 hours of life do not predict outcomeSerum cardiac Troponin T (cTnT)B-type natriuretic peptide (BNP)NTpBNP and cTnT in conjunction with echocardiography may provide a basis for trials of targeted medical treatment in infants with a PDA.Arch. Dis. Child. Fetal Neonatal Ed. published online 19 Feb 2008;
39 TreatmentPGE2 appears to be the most important factor regulating ductal patencyInhibition of PG synthesis by inhibition of the enzyme cyclooxygenase (COX) produces constriction of the DA
40 IndomethacinOver the years, therapy with indomethacin has been accepted as effective in mediating ductal closure in preterm neonates.Little consensus regarding proper dosage, treatment duration, and optimal timing of treatment.NeoReviews Vol.4 No.8 August 2003 e215
41 Indomethacin Dose & Timing The response of the ductus to indomethacin depends on the size of the dose and the number of doses administered.3 doses regimen Vs 5-6 doses (at 0 hours, 12 hours, 24 hours, 48 hours, and 72 hours).Continuous infusion (17 mcg/kg per hour over 36 h)
42 Indomethacin Treatment for Symptomatic Patent Ductus Arteriosus in Effectiveness and Side Effects of an Escalating, Stepwise Approach toPremature Infants Below 33 Weeks of Gestation Pediatrics 2005;116;
47 Authors’ conclusionsProlonged indomethacin course does not appear to have a significant effect on improving important outcomes, such as PDA treatment failure, CLD, IVH, or mortality.The reduction of transient renal impairment does not outweigh the increased risk of NEC associated with the prolonged course.
48 TimingPost-natal ageNear term infant PGE2 is not the dominant factor maintain ductus patency CottonBiol Neonate 60: ,1991Reopening of the duct 23% in <26wksEarly prophylaxis (90% borne <30 wk with NO PDA only 40% will develop significant PDA)
51 Complications of Indomethacin Decrease in glomerular filtration rateInhibits platelets and prolongs the bleeding timeFrank renal or gastrointestinal bleeding are contraindications to the use of indomethacin.Isolated cases of localized intestinal perforation & NEC? SepsisNeoReviews Vol.4 No.8 August 2003
52 IbuprofenIt is emerging rapidly as a potential alternative to indomethacinCausing less vascular compromiseMesenteric blood flowRenal perfusion.CBF
53 Safety and efficacy of ibuprofen Ibuprofen is as effective as indometacin for PDA treatment in extremely premature infantsNo increasing in the incidence of complications NEC, CLDFewer doses of drugs were needed to achieve acceptable closing rates.Arch Dis Child Fetal Neonatal Ed 2008;93:F94–F99. doi: /adc
56 ConclusionNo statistically significant difference in the effectiveness of ibuprofen compared to indomethacin in closing the PDA.Ibuprofen reduces the risk of oliguria.ibuprofen may increase the risk for CLD, and pulmonary hypertensionIndomethacin should remain the drug of choice for the treatment of a PDA.The Cochrane Collaboration 2007.
57 EBMWyllie J. Treatment of patent ductus arteriosus. Semin Neonatol2003;8:Thomas RL, Parker GC, Van Overmeire B, et al. A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. Eur J Pediatr2005;164:Shah SS, Ohlsson A. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants [Cochrane Review]. In: The Cochrane Library; Issue 2, Oxford: Update Software.Gournay V, Roze JC, Kuster A, et al. Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial. Lancet 2004;364:Van Overmeire B, Allegaert K, Casaer A, et al.; Multicentre Ibuprofen Prophylaxis Study (MIPS) Investigators. Prophylactic ibuprofen in premature infants: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet2004;364:Van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med2000;343:Gournay V, Savagner C, Thiriez G, et al. Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants. Lancet2002;359:
58 Undesirable adverse effect Increased vascular resistantIncrease the free fraction of bilirubin by a factor of four & the risk of bilirubin encephalopathyBPD and PPHNSpeziale MV, Allen RG, Henderson CR, Barrington KJ, Finer NN. Effects of ibuprofen and indomethacin on the regional circulation in newborn piglets. Biol Neonate. 1999;76:242–252
59 Concurrent Use of Furosemide It increases PG productionIt could decrease ductal response to indomethacin.Consequently, furosemide may have conflicting physiologic effects in the preterm infant who has PDAUsed only with signs of congestive HF and pulmonary congestionnot with fluid restriction and indomethacin or Ibu.Cochrane review 2004
60 Surgical ClosureIt is usually reserved for PDA refractory to medical managementProposed as a primary treatment of PDA and the treatment of PDA that responds poorly to indometacinLittle DC, Pratt TC, Blalock SE, et al. Patent ductus arteriosus in micropreemies and full-term infants: the relative merits of surgical ligation versus indometacin treatment. J Pediatr Surg 2003;38:492–6.
64 Future Directions NO Inhibition PGE2 Receptor Manipulation Vitamin A Other COX Inhibitors Less effective
65 SummaryPDA is a common complication of very low-birthweight infants who is recovering from RDSEarly diagnosis (ECHO)and treatment of homodynamic significant duct prevent major morbidityConservative treatment is visibleEither indo. Or IBU you need the duct closed with out the hand of surgeons