Case - Acute PH of the newborn / PPHN - January 2025

Case by Gabriel Altit - January 25, 2025

We describe the case of a term neonate born via cesarean section at term due to failure to progress in labor after prolonged rupture of membranes. The pregnancy was notable for maternal gestational diabetes mellitus and hypertension. Delivery was complicated by the presence of meconium-stained amniotic fluid, and the neonate required resuscitation at birth, including positive pressure ventilation and CPAP. Apgar were 3 and 4. The neonate was intubated due to severe respiratory distress and transferred to a tertiary care center for further management. On arrival, the neonate exhibited hypoxic respiratory failure requiring high-frequency oscillatory ventilation (HFOV) with an FiO2 of 100%. Initial evaluation was significant for findings suggestive of meconium aspiration syndrome, with chest radiography showing patchy, ground-glass opacities and evidence of stiff lungs requiring high ventilatory pressures. 

The neonate's management included sedation, umbilical line placement, and monitoring of hemodynamics and glucose levels. Surfactant was administered with no change in FiO2 requirements. We were asked to evaluate this patient by TnECHO. At 12 hours of life, the patient was on 70-75% FiO2 with no differential saturations (96% pre- and post-ductal). The patient was receiving low-dose dexmedetomidine for sedation/comfort since the baby would profoundly desaturate during manipulations/cares and suctioning of the tube. Blood pressure at the time of the TNE recorded at 60/40 mmHg, with a heart rate of 127 beats per minute. The neonate weight was 3kg. The baby was demonstrating adequate urine output of 4 mL/kg/hr. Arterial lactate was measured at 2.7 mmol/L, with blood gas values showing a pH of 7.38 and PaCO2 of 39 mmHg. The arterial oxygen partial pressure (PaO2) was 57 mmHg, measured from the umbilical artery line (UAL). The mean airway pressure was 12 cmH2O.

Due to findings consistent with acute pulmonary hypertension of the newborn (persistent pulmonary hypertension of the newborn), with a relatively preserved right ventricular function and output, the patient was initiated on inhaled Nitric Oxide per-TnECHO. The PFO and the PDA were bidirectional and the RV-RA by TRJ was 98 mmHg with appropriate angulation of the cursor to be parallel to the TR jet to capture the highest velocity through a CW-Doppler.  The RV was supra-systemic in systole. There was immediate response with oxygen needs dropping to 30-35% FiO2.

TnECHO was repeated on iNO 3 hours later and demonstrated at this point a completely left to right duct that was small and restrictive. The gradient was about 8 mmHg in systole - outlining that the systolic pulmonary arterial pressure was at this point 8 points lower than the systemic systolic blood pressure which was still in the 60s. 

Acute PH (Classical "PPHN") with significantly depressed cardiac function and restrictive ductus

Management:

1. Ensure appropriate ventilation, but avoid hypocapnia (cerebral vasoconstriction) 

   1. Surfactant for RDS or Meconium Aspiration Syndrome

   2. Appropriate pulmonary recruitment (being aware that increasing MAP can be problematic in terms of cardio-respiratory interactions; high MAP can increase RV afterload and decrease cardiac preload).

2. Sedation/Analgesia may be indicated to avoid reactive increase in PVR 

3. Oxygen should be administered to aim 90-95% saturation. Oxygen is a pulmonary vasodilator but also toxic when exposed in excess. 

   1. Due to right to left shunt, there is a threshold at which FiO2 increase has no impact and excessive O2 may cause lung injury by reactive oxygen species 

4. Despite optimization of status, still high PVR and hypoxic:

   1. iNO is one of the only agent studied in RCT for hypoxic respiratory failure (often with acute PH / PPHN) in the term and near-term newborns

   2. Wean if not working; Wean once phenotype changes/resolves (implies reassessments)

5. Increasing data that vasopressors like vasopressin and norepinephrine may improve the PVR/SVR ratio in acute PH. If does not respond to iNO (as first-line) - to consider.

6. PGE may be considered once PDA becomes restrictive as a pop-off for the RV (if there is RV failure). In the above case, the RV function and output seemed preserved. Despite a small and restrictive PDA, PGE were not initiated because the patient had good response to iNO. 

7. Hydrocortisone should be considered in certain situations

   1. We do not recommend necessarily to base on cortisol level - Challenge with cortisol is the aspect of relative adrenal insufficiency. What is the normal values of cortisol in the context of significant stress. We know that some of these babies may have adrenal ischemia, hemorrhage, immaturity or sepsis which may all overwhelm the adrenal function and response. I personally do not rely solely on cortisol values and often consider hydrocortisone in babies with significant hemodynamic derangements. 

   2. Appropriate response to stress essential for maintenance of hemodynamic stability. Glucocorticosteroids  adrenergic receptors in smooth muscles, inhibits NO synthase expression and ↓ reuptake of norepinephrine leading to an increase in vascular tone and support of myocardial function. Effective in increasing BP and decrease inotropic support. No study: improved clinical outcomes with steroids in newborn shock 

   3. Hydrocortisone normalizes PDE-5 activity in pulmonary artery smooth muscle cells from lambs with PPHN