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Pulmonary Hypertension in Newborns with Meconium Aspiration New Therapeutic Aspects

Pulmonary Hypertension in Newborns with Meconium Aspiration New Therapeutic Aspects. Pekka Kääpä, MD Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku. PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN). High pulmonary artery pressure

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Pulmonary Hypertension in Newborns with Meconium Aspiration New Therapeutic Aspects

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  1. Pulmonary Hypertension in Newborns with Meconium AspirationNew Therapeutic Aspects Pekka Kääpä, MD Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku

  2. PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN) • High pulmonary artery pressure • Right-to-left shunting • Hypoxemia • Low systemic arterial pressure

  3. PULMONARY HYPERTENSION OF THE NEWBORN • Incidence > 1:1000 births • Mortality 30-50% • Neurological sequelae 10-30% • Chronic lung injury ca. 25%

  4. DIAGNOSIS OF PULMONARY HYPERTENSION • Clinical signs (hypoxemia) • Clinical tests (pre-postductal pO2) • Doppler/ultrasound – examinations • Catheterization

  5. PULMONARY HYPERTENSION OF THE NEWBORN • Obstruction of the pulmonary vessels: • Idiopathic • RDS • Aspiration • Infection • Pulmonary vascular hypoplasia • High blood viscosity: • Infants of diabetic mothers

  6. MECONIUM ASPIRATION SYNDROME • Meconium-stained amniotic fluid in 10-15% of deliveries • Respiratory failure in 5% of infants, often connected with pulmonary hypertension • Mortality up to 40%

  7. PATHOPHYSIOLOGY OF MECONIUM ASPIRATION SYNDROME • Airway occlusion • Direct tissue injury • Pulmonary hypertension • Inflammation • Surfactant dysfunction

  8. MECONIUM ASPIRATION

  9. PULMONARY RESPONSES IN MECONIUM ASPIRATION • Immediate ventilation/perfusion mismatch - concentration dependent • Progressive pulmonary hypertension from 2 hours on - concentration dependent • Inflammatory changes and surfactant dysfunction in 4-6 hours • Tissue necrosis after 24-48 hours

  10. TREATMENT STRATEGIES IN MECONIUM ASPIRATION • Ventilatory assistance / oxygenation • Vasodilatory treatment • Anti-inflammatory drugs • Surfactant administration / lavage • ECMO

  11. TREATMENT STRATEGIES OF PULMONARY HYPERTENSION IN MECONIUM ASPIRATION • Ventilatory assistance / oxygenation • Vasodilatory treatment (-> NO) • Anti-inflammatory drugs (-> Dexa) • ECMO

  12. PULMONARY VASODILATORY TREATMENT • Tolazoline (1 mg/kg/h) • not selective, dilatory effect poor • hemorrhagies, hypotension, renal failures in 50-70% • Prostacyclin(PGI2)(10-60 ng/kg/min) • systemic hypotension • Inhaled nitric oxide (INO)

  13. INHALED NITRIC OXIDE (INO) IN MECONIUM ASPIRATION • Selective pulmonary vasodilation • Modulation of endothelial permeability • Attenuation of leucocyte function • Inhibition of platelet aggregation

  14. Nitric oxide in MAS

  15. Nitric oxide in MAS

  16. INO IN EXPERIMENTAL MECONIUM ASPIRATION • Author Model INO Response • ------------------------------------------------------Barrington Piglet 5-80ppm SO2 ,PAP • 1995 • Rais-Bahrami Piglet 10-40ppm SO2, PAP • 1997 Cuesta 1998 Lamb 20ppm PO2, PAP • Holopainen Piglet 1, 10 ppm PO2,PAP • 1999

  17. INO IN EXPERIMENTAL MECONIUM ASPIRATION • Transient or short-term improvement of oxygenation • Small or no reduction in pulmonary hypertension • Effects similar at different doses (5-80 ppm) • No clear effect on the ventilatory parameters or inflammatory lung tissue response

  18. INO IN CLINICAL MECONIUM ASPIRATION SYNDROME • Variable improvement of oxygenation (in about 50%) • Decreased need for ECMO • No reduction in mortality • Cochrane Database 2001 • Weinberger et al., Pharmacol Ther 2001

  19. INO IN MECONIUM ASPIRATION • Improves ventilation/perfusion matching • Effect on oxygenation and pulmonary vascular resistance variable • Severity of the parenchymal disease critical in the responsiveness to INO • --> Experimental mode of treatment

  20. TREATMENT STRATEGIES OF PULMONARY HYPERTENSION IN MECONIUM ASPIRATION • Ventilatory assistance / oxygenation • Vasodilatory treatment (-> NO) • Anti-inflammatory drugs (-> Dexa) • ECMO

  21. Steroids in MAS

  22. Steroids in MAS

  23. STEROIDS IN EXPERIMENTAL MECONIUM ASPIRATION • Author Model SteroidResponse • ----------------------------------------------------- • Franz 1975Rabbit HC survival • Soukka 1997 Pig MP (pre) FiO2,PAP ,PVR Khan 1999 Piglet DexaFiO2,compliance • Wu 1999 Piglet Dexa PAP • Holopainen Piglet Dexa (pre)FiO2,PAP PVR 2000

  24. STEROIDS IN CLINICAL MECONIUM ASPIRATION • No effect on oxygenation, ventilation or survival • (Yeh et al., 1977) • Improvement of oxygenation • (da Costa et al., 2001)

  25. STEROIDS IN MECONIUM ASPIRATION • Early steroid administration may improve the pulmonary function and oxygenation • Steroids may attenuate the inflammatory lung injury • Potential side-effects: hypertension, immunosuppression, poor neurological development (?) • --> Experimental treatment

  26. THERAPEUTIC APPROACH TO MECONIUM ASPIRATION WITH PPHN • Therapeutic effect of INO or steroids variable and generally poor • Combination of therapies, or addition of exogenous surfactant may be more effective • Potential side-effects may limit the use

  27. POOR THERAPEUTIC RESPONSE OF PULMONARY HYPERTENSION IN MECONIUM ASPIRATION • Selectivity of the vasodilators poor • Treatment of the lung disease insufficient • Continuous systemic hypotension

  28. FUTURE THERAPEUTIC ASPECTS OF MECONIUM ASPIRATION SYNDROME • New modes of therapy: • surfactant lavage • liquid ventilation • Early start of the therapy: • prophylactic • at birth / first hours • Preventive measures

  29. RESEARCH GROUP • Hanna Soukka, MD • Kalle Korhonen, MD • Minna Aaltonen, MD • Jaakko Kytölä, MD • Heikki Lukkarinen, BM • Jani Lehtonen, BM • Aida Steiner, BM

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