PH in bronchopulmonary dysplasia

Adapted from literature - Recommendations and Review

Premature infants should have an echocardiogram performed to screen for PH in the following scenarios:

1. At the time of formal BPD diagnosis as per current practice (36 weeks postmenstrual age.

2. Severe hypoxemic respiratory failure shortly after birth attributed primarily to persistent pulmonary hypertension of the newborn (PPHN) physiology despite optimal management of underlying lung disease.

3. Continued need for ventilator support at postnatal day 7, as echocardiogram evidence of PH at day 7 suggests high risk for BPD and may alter therapy.

4. With sustained need for significant respiratory support at any age, especially with recurrent episodes of hypoxemia.

Normal Pulmonary artery (PA) pressure = 15/5 (mean of 10) after 3 months of age

• First 3 months: PVR dropping and should be < systemic.

Abnormal PA pressure defined:

• Mean PAP ≥ 20 mmHg (2018 definition, before 25 mmHg – measured by catheterization but can be estimated by echo), or

• Systolic PAP ≥ 40 mmHg (estimated by Echo), using:

• TRJ ≥ 35 mmHg (assuming a Right Atrial pressure of 5)

PH is usually assumed by echocardiography if any of the following present:

· a mean pulmonary arterial pressure (mPAP) estimate ≥ 20 mmHg (using a pulmonary insufficiency jet) or

· an estimated systolic pulmonary arterial pressure (sPAP) ≥ 40 mmHg. sPAP estimated by echocardiography using either:

1. tricuspid regurgitant jet (TRJ) ≥ 35 mmHg (plus expected right atrial pressure of 5 mmHg), when a full Doppler envelope is available,

2. Restrictive ventricular septal defect (VSD) or patent ductus arteriosus (PDA) velocity gradient.

3. A ratio of the estimated sPAP to the systemic systolic blood pressure (sBP) at the time of the echocardiography is important to compare the two compartments

· Flattening of the septum at the end of systole is a subjective surrogate of increased pulmonary pressure – indicating that there is relative iso-systemic pulmonary pressures (around 2/3 of systemic).

1. Round LV simply tells you that the systolic RV pressure is less than systolic LV pressure (but the sPAP could still be higher than normal).

2. Isosystemic = Flat Interventricular septum at peak of contraction. D-Shape LV (Type 2)

3. Supra-systemic = Bowing septum into the LV cavity (Type 3)

ATTENTION: It the setting of a large unrestrictive PDA – the PDA will expose the pulmonary circulation to systemic pressures in systole and diastole (like a window connecting the Aorta to the Pulmonary Artery). PDA is a Pressure lesion and a Flow lesion (excessive flow Qp>Qs; and excessive pressure in the pulmonary vascular compartment). As such, if the PDA is left to right – even if the TR is high – it could only represent this transmission of pressure and does not tell you a lot of information on underlying pulmonary vascular remodelling. Do not start pulmonary vasodilators because it will lead to further flow (while not changing the pressure since the PDA is a structural lesion). If the PDA is right to left – the PVR are higher than the SVR – in that setting there is supra-systemic pulmonary pressures. In the context of Bidirectional PDA – there is isosystemic pressures. A bidirectional PDA shunt at 36 weeks is worrisome for underlying pulmonary vascular disease. The same concepts apply to a large unrestrictive VSD (except that the VSD is a SYSTOLIC pressure and volume lesion, and only a DIASTOLIC volume lesion).

Infants with suspected PH by ECHO should get a full evaluation of LV and RV function, presence of cardiac or extra-cardiac shunts, pulmonary venous drainage, mitral valve disease and other left-sided heart disease.

Echocardiography to consider in BPD-PH assessment

PH Severity by Echocardiography

Further evaluation:

Further evaluation and treatment of comorbidities that impact the severity of lung disease should be undertaken with the diagnosis of BPD-PH infants before the initiation of pulmonary arterial hypertension (PAH)-targeted therapy. Studies should include:

· evaluation for intermittent or sustained hypoxemia (oxymetry),

· aspiration (evaluation by OT, consider videofluoroscopy, consider jejunal feeds trial)

· gastroesophageal reflux disease evaluation and treatment,

· structural airways disease with scope by ENT

· Have ECG and CXR baseline at diagnosis of pulmonary hypertension at 36 weeks.

· Consider NT-proBNP level for follow-up in patients with right ventricular dysfunction at diagnosis of pulmonary hypertension

· pulmonary artery and vein stenosis evaluation, left ventricular diastolic dysfunction, and aortopulmonary collaterals.

Management of BPD-PH:

· Consider trial of Naso/Oro-jejunal feeds to avoid silent micro-aspiration

· Optimize respiratory care (suctioning, recruitment with maximal functional residual capacity to avoid V-Q mismatch)

· Consider diuretics (Hydro/Spiro) in the context of pulmonary hypertension in BPD

· Consider

· Aim saturations ³ 92% for > than 95% of time. Supplemental oxygen therapy should be used to avoid episodic or sustained hypoxemia and with the goal of maintaining oxygen (O2) saturations between 92%- 95% in patients with established BPD and PH. Avoids vasculature vaso-spasm.

· Vaccination for avoidance of pulmonary infections

· Optimize nutrition (less volume more concentrate, aim normal weight/length ratio)

· Severe flare-up with viral / respiratory infections: require rigorous vaccination, avoidance of crowded areas (shopping center, kindergarten).

· Prevnar 13, Synagis, Pneumovax (23 serotypes polysaccharide vaccine) at 2 years

· Influenza vaccine for the whole family and patient > 6 months

· Ensure with oximetry that baby has saturation ³ 92 % for > 95% of the time

· Pulmonary vasodilators should be started with consultation of a pediatric cardiologist in the context of RV dysfunction and/or iso to supra-systemic pulmonary hypertension after optimization of everything above.

If BPD with severe PH goes into PH crisis – Algorithm:

• Patient in acute PH crises - Heterogeneous pulmonary vascular disease with V/Q mismatch

• Consider Re-intubation with sedation, aggressive chest physio and airway toilette + recruitment to minimize V/Q mismatch - Optimize ventilation with “BPD parameters” (long I-Time for CO2 release, lower rate, higher volumes). These lungs are fibrosed with airway disease that tend to collapse. They need usually a higher PEEP (8-10) in order to stent the airway.

• Optimize hemoglobin > 100

• iNO 20 ppm – will reach vessels of lung areas that are ventilated

• Milrinone – Lusitropic medication to promote RV function and filling

• If PH crisis, consider stress dose hydrocortisone 30 mg/m2/day

• Rule out concomitant infection +/- Abx (urine, viral, bacterial, pneumonia, etc.)

• Adjust nutrition, possibly induce diuresis with furosemide if oedema.

• BPD patients that are intubated and sedated do not need as much calories (the ventilator does much of the work and the sedation keeps them from activating metabolic rate). Need to avoid an increase in fat content and consider decreasing significantly calories and fluids.

For home or follow-up (intra-hospital if still hospitalized):

• Home Oxygen needs to be organized for pulmonary hypertension patients

• Parents need to be informed that the whole family needs influenza vaccination

• The patient should not be in kindergarten while still on home oxygen. Avoid spaces with close contacts. Avoidance of viral infection (social distancing).

• Parents need to be trained to recognize signs of resp distress or RV failure: diaphoresis, retraction, work of breathing, cyanosis, abnormal neurological status

• Parents need basic CPR training

• Travelling by plane can be complicated by PH crises – needs assessment for fit to travelling with hypoxic challenge once PH infra-systemic and stable in room air.

• Sildenafil can accentuate GERD, ensure to manage reflux and follow growth: avoid abnormal Weight-Length Ratio. Energy needs can be up to 140 kcal/kg/d (Small volumes but high caloric enrichment).

• Follow Hgb (ensure no anemia), regular blood gaz and electrolytes (especially if on diuretics), +/- Brain Natriuretic peptide if RV failure (baseline and at follow-ups).

• Consider: Sweat test, occasional chest X-ray to rule out aspiration (especially if oral challenges) and CT scan of chest if progressive worsening of clinical status.

Presentation on pulmonary hypertension and cardiac dysfunction in BPD by NeoCardioLab

Pediatric Pulmonary Hypertension Guidelines by AHA / ATS

Pulmonary hypertension in bronchopulmonary dysplasia - European Pediatric Pulmonary Vascular Disease Network (EPPVDN)

New Guidelines for Managing Pulmonary Hypertension: What the Pediatrician Needs to Know

Another great article is: "Evaluation and Management of Pulmonary Hypertension in Children with Bronchopulmonary Dysplasia" by PPHNET.