Late pulmonary hypertension in preterm infants How to sort things out? V.Gournay, FCPC, La Martinique, Nov 23,2015
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1 Late pulmonary hypertension in preterm infants How to sort things out? V.Gournay, FCPC, La Martinique, Nov 23,2015
2 Epidemiology Incidence of extreme prematurity (<28 WA) 0.4% Advances in neonatal care (surfactant) Increasing survival rate of the extremely low birth weight (ELBW) infants (75% in 26 WA) Stable rate of bronchopulmonary dysplasia (BPD)
3 BPD incidence according to gestational age 100 DBP = O 2 use> 28 days % of preterms with BPD < >30 gestational age
4 Normal pulmonary growth Pulmonary growth Canalicular stage (24-26 WA) Saccular stage (26-32 WA) Alvéolar stage (> WA) Birth 8 years
5 Pulmonary growth in the preterm Baraldi et Filippone, Lancet 2007;357:1946
6
7 Interaction between vascular and alveolar growth Thébaud et Abman, AJRCCM 2007;175:978
8 Interaction between vascular and alveolar growth Thébaud et Abman, AJRCCM 2007;175:978
9 Pulmonary hypertension (PHT) and BPD TOPP registry (Berger RM et al, Lancet 2012): 12% of pediatric PH associated with respiratory disease (BPD +++) Ill-defined incidence: 18% of ELBW prospectively screened at 28 days (Bhat R et al, Pediatrics 2012 ) Risk factors Small for gestational age Premature rupture of the membranes (oligohydramnios) Prolonged mechanical ventilation Hyperoxia (inflammation and oxidative stress)
10
11 Pathophysiology of PHT in BPD Decreased growth Hirschi KK et al, Circ Res 1999;84:298
12 Pathophysiology of PHT in BPD Altered structure: vascular remodeling
13 Pathophysiology of PHT in BPD Altered vasoreactivity Cardiac catheterization 10 children with BPD + PHT Mean age 5 years Mourani et al. AJRCCM 2004;170:1006
14 Screening strategy Echocardiography (Mourani P, Pediatrics 2008;121:317): Sensitivity for the presence of PHT 88% Who to screen? Extreme prematurity (GA <25 WA and/or BW <600g) Small for gestational age Unusually prolonged requirement for mechanical support Oxygen requirement at 36 WA When to screen? At 36 WA and/or before discharge At 28 days in high-risk infants???
15 Aggravating factors Extracardiac factors Gastroesphageal reflux Upper airway obstruction Malnutrition Cardiac factors Left-to-right shunts (PDA, MAPCAs, ASD) Pulmonary venous stenosis Left ventricular diastolic dysfunction
16 Pulmonary venous stenosis Associated with prematurity and BPD (Drossner D et al, Pediatrics 2008;122:e656) Odds Ratio 10.2 (95% CI , p<0.001) Acquired lesion, resulting from remodeling of the pulmonary venous bed Associated with L-R shunt 88% Unrecognized by echocardiography in 30% Left lower PV most commonly involved Poor survival
17
18 Management Optimization of respiratory function +++ Target O 2 saturation > 92% Overnight oximetry studies and carbon dioxide levels Good nutrition Prevention of viral infections (RSV +++) Follow-up Serial echocardiography until normalization (2-4 month intervals) Echocardiography 8-10 days after weaning off O 2
19 Catheterization Indications Significant PHT despite optimal management Need for assessment of vasoreactivity before initiation of pulmonary vasodilator therapy Suspicion of associated cardiac lesions +++ Evaluation of a left-to-right shunt Methods General anesthesia or conscious sedation Assessment of mpap, PCWP, QP/QS, PVR/SVR Pulmonary vascular reactivity testing with 100% oxygen followed by inhaled NO
20 Khemani E et al, Pediatrics 2007;120:1260
21 Pulmonary vasodilators Oral sildenafil (Mourani P, J Pediatr 2009;154:379) Retrospective study on 25 patients Initiation at 171 (14-673) days of age 0.5 mg/kg/8h increased up to 2 mg/kg/8h Median duration of sildenafil use 241 days Significant improvement (20% decrease in the ratio of P/S SAP) after 40 (6-600) days in 88% of the patients 5 deaths Adverse reactions in 2 patients
22 Mourani P, J Pediatr 2009;154:379
23 Outcome Khemani E et al, Pediatrics 2007;120:1260 Median duration of follow-up 9.8 months Improvement in PHT severity in 89% patients Predictive factors of death Severe PHT (systemic or suprasystemic RV pressure) at the time of PHT diagnosis or at any time during the study period Small for gestational age Previous support with HFO at any time
24 Survival Khemani E et al, Pediatrics 2007;120:1260
25 Conclusion PHT incidence 20% ELBW infants Mostly due to impaired vascular growth and reactivity Resolution with optimized respiratory care in most cases Echocardiography is the mainstay of screening and monitoring Cardiac catheterization indicated if Cardiac aggravating factors are suspected: Any significant left to right shunt Pulmonary venous stenosis Pulmonary vasodilator therapy is considered
26
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