Persistent fetal circulation

Persistent Fetal Circulation: PPHN - Management, ECHMO.

1. PERSISTENT FETAL CIRCULATION By Dr Robin Thomas Resident in Pediatrics JJMMC, Davangere

2. Defn :Disruption of normal perinatal to neonatal circulatory transition-sustained elevation in Pulmonary vascular resistance . Risk for chronic pulmonary disease & neurodevelopmental disabilities. Incidence: 1-2 per 1000 live births. Perinatal risk factors: MSAF, Maternal condn - fever, anemia, pulmonary d/s Maternal D.M, U.T.I during pregnancy, SSRIs, aspirin, NSAIDS & C.S PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN

3. Rapid fall in pulmonary vascular resistance (PVR)- first breath & increase in systemic vascular resistance (SVR) –clamping of umbilical cord. Circulating biochemical mediators - increased arterial O2 content & pH & lowered PaCO2 –constriction of ductus - arteriosus & vasorelaxation of pulmonary circulation. Perinatal circulatory transition

4. Physiological events raise SVR relative to PVR –functional closure of foramen ovale . Persistent fetal circulation -mimics fetal circulation-PVR exceeds SVR & right to left hemodynamic shunting occurs tru foramen ovale or ductus arteriosus . Dimnished pulmonary perfusion & systemic hypoxemia.

5. Persistant fetal circulation

6. 1.Severe fetal hypoxemia (Birth asphyxia ) –common association Prolonged fetal stress & hypoxemia –remodeling & abnormal muscularization of pulmonary arterioles. Acute birth asphyxia-release of vasoconstricting humoral factors & suppression of pulmonary vasodilators-pulmonary vasospasm. Risk factors

7. 2.Pulmonary parenchymal diseases -surfactant deficiency, pneumonia, MAS. Fetus with advanced gestational age. 3.Abnormalities of pulmonary dvp . – PPHN Congenital diaphragmatic hernia, Porter syndrome, Pulmonary parenchymal hypoplasia -pruning of vascular tree. Alveolar capillary dysplasia- malalignment of pulmonary veins & arteries.

8. 4.Myocardial dysfunction , myocarditis , intrauterine constriction of ductus arteriosus , severe congenital heart disease-PPHN. 5.Pneumonia or sepsis of bacterial or viral orgin -PPHN. Suppression of endogenous NO production. endotoxin mediated myocardial depression, pulmonary vasoconstriction assoc. with release of thromboxanes .

9. 6.Familial recurrence-uncommon , infants with PPHN –low plasma levels of arginine & NO metabolites & specific polymorphism at 1,405 position of carbamoyl phosphate - synthetase gene .

10. 1.Pulmonary vascular remodelling -abnormal muscularization of non muscular intra- acinar arteries with increased medial thickness of larger muscular arteries-decreased cross sectional area of pulmonary vascular bed & elevated PVR. Fetal hypoxemia-stimulus for pulmonary vascular remodelling . Pathophysiology

11. Humoral growth factors released by hypoxia damaged endothelial cells promote vasoconstriction & overgrowth of pulmonary vascular muscular media. Vascular changes –fetal exposure to NSAIDS- cause constriction of fetal ductus arteriosus & fetal pulmonary overcirculation .

12. 2.Pulmonary hypoplasia Affects both alveolar & pulmonary arteriolar dvp .-congenital diaphragmatic hernia, oligohydramnios syndrome, Porter syndrome (renal agenesis). 3.Reversible pulmonary vasospasm Infants with nonfatal PPHN. Hypoxia induces pulmonary vasoconstriction – acidemia . Neural & humoral vasoactive substances.

13. Suppression of endogenous NO, prostacyclin or bradykinin production & release of thromboxanes (A2,B2) , leukotrienes (C4,D4)- increased PVR – Sepsis & hypoxemia . 4. Myocardial dysfunction with elevated PVR - 1.Right ventricular dysfunction- Intrauterine constriction of ductus arteriosus -post natal pulmonary hypertension, RV failure, atrial R-L shunt.

14. 2.Left ventricular dysfunction-pulmonary venous hypertension & secondary pulmonary arterial hypertension-right to left shunting through ductus arteriosus . 5.Mechanical factors Cardiac output & blood viscosity. Low cardiac output-fewer pulmonary arteriolar channels & raises PVR. Hyperviscosity with polycythemia -reduces pulmonary microvasculature perfusion.

15. Physical examn -cyanosis, prom. Precordial impulse, single or narrowly split & accentuated S2 , systolic murmur. Invest. 1.Gradient of 10 % or more in oxygen saturation b/w preductal & postductal ABG or transcutaneous O2 saturation- ductus - arteriosus right to left hemodynamic shunt & absence of structural heart disease-PPHN Diagnosis

16. CXR -normal /assoc. pulmonary parenchymal d/s. ECG -RV predominance-cons. normal for age. ECHO -hemodynamic shunting, evaluate ventricular function, exclude congenital heart disease. TR or flattened ventricular septum in ECHO-PPHN.

17. Color doppler examn.-intracardiac or ductal hemodynamic shunting. Continuous wave doppler sampling of velocity of TR jet-estimate pulmonary artery presures .

18. Cyanotic congenital cardiac disease over PPHN: cardiomegaly grade3 murmur weak pulses active precordium pulmonary edema pulse differ.b /w upper & lower extremities persistent preductal & postductal arterial O2 tension less or equal to 40 mmHg.

19. Aim: reverse hypoxemia, improve pulmonary & systemic perfusion, preserve end organ function. Adequate respiratory support- normoxemia & neutral to slightly alkalotic acid base balance –facilitate normal perinatal circulatory transition. Management

20. 1.Supplemental O2 : Hypoxia-powerful pulmonary vasoconstrictor Preductal & post ductal SaO2 should be monitored. Supplemental O2 –reduce abnormally elevated PVR, minimize end organ underperfusion & lactic acidemia . Maintain post ductal SaO2 >90%-ensure tissue oxygenation & <98% to avoid hyperoxemia .

21. 2.Intubation & mechanical ventillation : Hypoxemia persists despite maximal O2 admns . or respiratory failure-marked hypercapnia & acidemia . Maintain PaO2 & PaCO2 values & avoid hyperoxia & hyperventilation. Target goals: SaO2 90-98%, PaCO2 40-50 mmHg, pH 7.30-7.40

22. a. PPHN with pulmonary parenchymal d/s- HFOV high frequency oscillatory ventillation or HFJV high frequency jet ventillation . HFJV-useful for meconium aspiration pneumonitis & air leak. HFOV-deliver iNO . b.Absence of pulmonary disease- High intrathoracic pressure impedes cardiac output & elevates PVR.

23. HFJV

24. HFOV

25. Strategy for mechanical ventillation -rapid, low pressure, & short inspiratory time-minimize elevated intrathoracic pressure. 3.iNO –produced by endothelial cells. diffuses into smooth muscle cells, increases intracellular cGMP , relaxes vascular smooth muscle & causes pulmonary vasodilation .

26. iNO –HFOV-doses of 1-20 parts per million- causes pulmonary vasodilation -not systemic- vasodilation –decreases PVR. Methemoglobinemia -serious potential toxicity of iNO Rx. Measure metHb levels 24 hrs after start of Rx. metHb levels>7% -reduce iNO Rebound hypoxemia-if iNO discontinued abruptly. iNO should be tapered very gradually.

27. Starting dose of iNO is 20ppm-delivered via ventilator circuit. As baby improves & inspired O2 conc.<50%- iNO is tapered by halving the dose. eg : 20 to10 to 5 ppm over a 12-24 hr period -gradually to 2 then 1 ppm . iNO –given in infants with PPHN & diffuse pulmonary disease by concomitant use of HFOV & surfactant treat.

28. Sildenafil Phosphodiesterase-5 inhibitor Increases endogenous NO by inhibiting metabolism-Rx for PPHN Randomized clinical trials awaited.

29. 4.ECMO Absence of pulmonary hypoplasia -ECMO- life saving therapy for 75-85% infants with PPHN who fail conventional management or iNO . ECMO criteria- Alveolar arterial O2 difference (AaDO2) >600 or Oxygenation index(OI) >30 on two ABGs >30 min apart. Brief trial of HFOV or iNO instituted before ECMO.

30. Technique of life support for neonates –cardiac or respiratory failure-not responding to conventional therapy. Indications: Respiratory failure-reversible, Cardiac failure, E-CPR, Ex utero intra partum treatment to ECHMO. Contra. Irreversible brain damage, intraventricular & intraparenchymal hemorrhage, wt<1.5kg, gestat . age<34wk, congenital abn . severe coagulopathy , continuous CPR >1hr. ECMO

31. ECMO

32. ECMO - video

33. ECMO

34. 5.Sedation & analgesia Fentanyl 1-4 micro gm/kg/hr infusion Morphine sulphate 0.05-0.1 mg/kg/hr infusion-infant should not be hypotensive . 6.Metabolic alkalosis Neutral to alkalotic pH-physiologic stimulus that reduces PVR. Normalize pulmonary gas exchange & conservative use of sodium bicarbonate.

35. 7.Hemodynamic support a.Volume expansion 0.9 % NS 10ml/kg over 20-30 min-used in hemorrhage or excessive capillary leak, Packed red blood cells also used. Infants with marked capillary leak-avoid 5% albumin-albumin also leaks from capillaries –worsen intertitial edema.

36. b.Pharmacologic Rx 1.Cardiotonic agents- Dobutamine 2.Vasopressors-Dopamine, Epinephrine. Milrinone -cardiac function very poor & infant unresponsive to dobutamine . enhances cardiac output & lowers PVR.

37. Dobutamine -beta1 adrenergic stimulation. Dopamine -alpha & beta adrenergic receptor stimulation. Support of systemic BP & improved cardiac output. High dose 6-20 micro gm/kg/min Moderate dose 3-5 micro gm/kg/min Low 1-2 micro gm/kg/min- enhances mesenteric & renal blood flow. Dopamine may increase PVR-high infusion rates >10micro gm/kg/min.

38. Epinephrine 0.03-0.10 micro gm/kg/min-stimulates alpha & beta adrenergic receptors. Raises systemic BP tru enhanced cardiac output & peripheral vasoconstriction. Epinephrine infusion caution-alpha adrenergic receptor stimulation results in pulmonary vasoconstriction & elevated PVR & end organ (renal & mesenteric) perfusion reduced.

39. 8.Correction of metabolic abnormalities Biochemical abnorm .-right to left shunting by imparing cardiac function. Correction of hypoglycemia & hypocalcemia –proper myocardial function. 9.Correction of Polycythemia Hyperviscosity assoc. with polycythemia –increases PVR –release of vasoactive substances tru platelet activation.

40. Partial exchange transfusion -central hematocrit exceeds 65%. 10.Additional pharmacological agents Sildenafil , adenosine, magnesium suphate , calcium channel blockers, inhaled prostacyclin , inhaled ethyl nitrite, inhaled or inravenous tolazoline . Data insufficient to support use of these medications.

41. 11.Treatment contraversies Interinstitutional variations in approach to diagnosis & management of PPHN. Few centres report successful Rx without use of mechanical ventillation , iNO , ECMO.

42. PPHN results from disruption of normal perinatal fetal to neonatal circulatory transition. Incidence 1-2 per 1000 live births. Sustained elevation of PVR Persistent fetal circulation Contemporary ventilator management,iNO , ECMO have improved survival among infants with PPHN. Summary

43. Survivors of PPHN are at risk for chronic -pulmonary disease , audiological , neurodevelopmental or cognitive impairments.

44. 1.Kliegman, Stanton, Geme ST, Schor , Behrman. Nelson Textbook of Pediatrics 19 th edition ,2012 :1529-1530. 2.Cloherty PJ, Eichenwald CE, Hansen RA, Stark RA. Manual of Neonatal Care 7 th edition, 2012 : 435-442 3.John FK, James EL, Donald CF. Nadas Text book of Cardiology 2 nd edition 2006 :113-125 4.Myung PK .Pediatric cardiology for Practitioners 2012, 5 th edition:120-124 References