Persistent Pulmonary Hypertension of the Newborn (PPHN) Fred Hill, MA, RRT.
Pphn mas Eesti
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Pulmonary Hypertension in Newborns with Meconium
Aspiration
New Therapeutic Aspects
Pekka Kääpä, MDResearch Centre of Applied and Preventive Cardiovascular Medicine,University of Turku
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PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN)
High pulmonary artery pressure
Right-to-left shunting
Hypoxemia
Low systemic arterial pressure
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PULMONARY HYPERTENSION OF THE NEWBORN
Incidence > 1:1000 births
Mortality 30-50%
Neurological sequelae 10-30%
Chronic lung injury ca. 25%
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DIAGNOSIS OF PULMONARY HYPERTENSION
Clinical signs (hypoxemia)
Clinical tests (pre-postductal pO2)
Doppler/ultrasound – examinations
Catheterization
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PULMONARY HYPERTENSION OF THE NEWBORN
Obstruction of the pulmonary vessels: Idiopathic RDS Aspiration Infection
Pulmonary vascular hypoplasia
High blood viscosity: Infants of diabetic mothers
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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%
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PATHOPHYSIOLOGY OF MECONIUM ASPIRATION SYNDROME
Airway occlusion Direct tissue injury Pulmonary hypertension Inflammation Surfactant dysfunction
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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
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TREATMENT STRATEGIES IN MECONIUM ASPIRATION
Ventilatory assistance / oxygenation
Vasodilatory treatment
Anti-inflammatory drugs
Surfactant administration / lavage
ECMO
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TREATMENT STRATEGIES OF PULMONARY HYPERTENSION IN MECONIUM ASPIRATION
Ventilatory assistance / oxygenation
Vasodilatory treatment (-> NO)
Anti-inflammatory drugs (-> Dexa)
ECMO
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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)
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INHALED NITRIC OXIDE (INO) IN MECONIUM ASPIRATION
Selective pulmonary vasodilation
Modulation of endothelial permeability
Attenuation of leucocyte function
Inhibition of platelet aggregation
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Nitric oxidein MAS
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Nitric oxidein MAS
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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
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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
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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
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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
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TREATMENT STRATEGIES OF PULMONARY HYPERTENSION IN MECONIUM ASPIRATION
Ventilatory assistance / oxygenation
Vasodilatory treatment (-> NO)
Anti-inflammatory drugs (-> Dexa)
ECMO
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Steroids in MAS
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Steroidsin MAS
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STEROIDS IN EXPERIMENTAL MECONIUM ASPIRATION
Author Model Steroid Response ----------------------------------------------------- Franz 1975 Rabbit HC survival
Soukka 1997 Pig MP (pre) FiO2,PAP ,PVR
Khan 1999 Piglet Dexa FiO2,compliance
Wu 1999 Piglet Dexa PAP
Holopainen Piglet Dexa (pre) FiO2,PAP PVR
2000
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STEROIDS IN CLINICAL MECONIUM ASPIRATION
No effect on oxygenation, ventilation or survival
• (Yeh et al., 1977)
Improvement of oxygenation• (da Costa et al., 2001)
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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
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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
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POOR THERAPEUTIC RESPONSE OF PULMONARY HYPERTENSION IN MECONIUM ASPIRATION
Selectivity of the vasodilators poor
Treatment of the lung disease insufficient
Continuous systemic hypotension
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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
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RESEARCH GROUP
Hanna Soukka, MD Kalle Korhonen, MD Minna Aaltonen, MD Jaakko Kytölä, MD Heikki Lukkarinen, BM Jani Lehtonen, BM Aida Steiner, BM