Case January 2026
Acute PH and Pulmonary Hemorrhage

We report a late-preterm infant with perinatal asphyxia who developed early-onset persistent pulmonary hypertension of the newborn (PPHN) accompanied by a biventricular dysfunction phenotype, followed by pulmonary hemorrhage likely precipitated by elevated left atrial (LA)/pulmonary venous pressure in the context of impaired left ventricular (LV) systolic function.

Case presentation

A late-preterm (34+6 weeks), appropriate weight for gestational age was delivered by cesarean section for maternal chronic hypertension with superimposed preeclampsia (severe features) and non-reassuring fetal status. Following routine resuscitation, he was admitted to the NICU on nasal CPAP level at 7 cmH2O with 40% FiO2 for respiratory distress. He was initially lethargic with severe metabolic acidosis on cord gas (pH 6.9, PCO₂ 102 mmHg, HCO₃ 22 mmol/L, base excess −11) and hypoglycemia; examination suggested mild-to-moderate hypoxic–ischemic encephalopathy. After glucose correction, neurologic status improved to mild encephalopathy, and bedside aEEG demonstrated continuous normal voltage; therapeutic hypothermia was not initiated given gestational age and clinical improvement on the modified Sarnat assessment.
 

At 6 hours of life, he acutely deteriorated with worsening hypoxemic respiratory failure (FiO₂ up to 0.85) and differential cyanosis, with borderline systemic blood pressure (arterial BP; 50/28 (36) mmHg). Echocardiography demonstrated a depressed LV ejection fraction (39%) and pulmonary hypertension with near-systemic right-sided pressures (RVSP ~41 mmHg when systemic BP was 51/29 mmHg), along with a moderate PDA (3.3 mm) with bidirectional shunting. He was intubated to optimize ventilation, and dobutamine was initiated and titrated to 15 µg/kg/min. Because his systemic blood pressure remained at approximately the 5th percentile and cardiac function did not improve with dobutamine, an epinephrine infusion (0.1 µg/kg/min) was started overnight, together with intravenous hydrocortisone.

At ~18 hours of life, he developed pulmonary hemorrhage with severe oxygenation failure, prompting escalation to high-frequency oscillatory ventilation (MAP titrated to 21 cmH₂O), alongside blood product transfusion and surfactant therapy. By day 3, pulmonary hemorrhage persisted and pulmonary hypertension worsened (RVSP 79 mmHg with systemic BP 67/39 mmHg); milrinone was commenced (maximum 0.4 µg/kg/min) and dobutamine discontinued. Nebulized tranexamic acid was administered every 8 hours, after which hemorrhage gradually resolved after 2 days of nebulization and milrinone was stopped by DOL 7 with normalization of the cardiac findings.

Targeted Neonatal Echocardiography 1

3 hour after birth before intubation and intitation of cardiovascular medications. Some concern for LV function based on overall appreciation, Shortening fraction of 18% and decreased LV output estimation. 

Targeted Neonatal Echocardiography 2

TnECHO on Dobutamine 10 mcg/kg/min and epinephrine 0.1 mcg/kg/min. Dobutamine and eventually epinephrine were initiated to support the biventricular function during this transitional period. 

Targeted Neonatal Echocardiography 3

Dobutamine of 5 mcg/kg/min and Epinephrine 0.1 mcg/kg/min

Right ventricular systolic performance appeared relatively preserved by qualitative assessment and TAPSE, despite moderate tricuspid regurgitation. In the face of left atrial dilatation, suggesting high LA pressure, the bidirectional shunting at the atrial level also suggested elevated right atrial pressure. This was felt to be exacerbated by high mean airway pressure during high-frequency oscillatory ventilation.

Given this integrated physiology, initiation of inhaled nitric oxide was deliberately avoided. Selective pulmonary vasodilation was felt to carry a high risk of further increasing pulmonary blood flow and capillary hydrostatic pressure, thereby exacerbating pulmonary hemorrhage. Similarly, dopamine was avoided due to its known potential to increase pulmonary vascular resistance, while vasopressin was not favored given concern for worsening left ventricular loading conditions. Ventilatory strategy focused on stabilization rather than recruitment. High-frequency oscillatory ventilation was used to tamponade alveolar bleeding and stabilize gas exchange, while recognizing that excessive mean airway pressure could further impair ventricular filling and promote right-to-left atrial and ductal shunting. A gradual reduction in mean airway pressure was therefore recommend. Hemodynamic support was tailored to maintain systemic and coronary perfusion while minimizing further increases in heart rate and afterload. Epinephrine and stress-dose hydrocortisone were continued transiently to support blood pressure and myocardial perfusion. Dobutamine was viewed cautiously, as its chronotropic effects were felt to potentially worsen left ventricular end-diastolic pressure and transmit further pressure to the left atrium; reduction and eventual discontinuation were recommended once alternative support could be established. Milrinone was identified as a physiologically aligned. Its lusitropic properties and ability to improve ventricular relaxation were felt to offer a theoretical advantage in reducing left ventricular filling pressures and left atrial pressure, thereby addressing a key driver of pulmonary venous congestion. For this reason, milrinone was recommended in preference to escalating catecholamine support, with concomitant reduction in dobutamine.

Given ongoing active pulmonary hemorrhage, inhaled tranexamic acid was recommended as a rescue adjunct to stabilize alveolar bleeding while avoiding the systemic and pulmonary hemodynamic effects associated with endotracheal epinephrine. Its use was considered temporizing and supportive, intended to allow time for correction of the underlying hemodynamic contributors to hemorrhage rather than as definitive therapy. Finally, given the severity of hypoxemic respiratory failure, suprasystemic pressure estimates, and escalating support, early consideration of extracorporeal life support readiness was advised, including timely neuroimaging, recognizing that the infant was approaching institutional thresholds for ECMO candidacy. The subsequent rapid resolution of pulmonary hemorrhage and improvement in oxygenation following implementation of this strategy supports the central premise that the dominant pathophysiology was pressure-transmitted and post-capillary pulmonary hypertension rather than primary pulmonary vascular constriction. This case underscores the value of serial, integrative targeted neonatal echocardiography to distinguish pulmonary vascular phenotypes in complex transitional states and to guide individualized, physiology-aligned management.

Rational by agents using a neonatal hemodynamics mindset

• Inhaled nitric oxide (iNO) was deliberately avoided. Selective pulmonary vasodilation was felt likely to increase pulmonary blood flow and pulmonary capillary pressure, thereby worsening ongoing pulmonary hemorrhage. iNO was therefore considered potentially harmful rather than beneficial.

• Dobutamine was used cautiously and not escalated. While dobutamine can improve contractility, its chronotropic effects were a concern in this infant with impaired diastolic accommodation and elevated left ventricular end-diastolic pressure. Increasing heart rate was felt likely to shorten diastolic filling time, worsen LV filling pressures, and further transmit pressure to the left atrium and pulmonary veins. For this reason, higher doses were discouraged and discontinuation was recommended once an alternative strategy to support ventricular relaxation could be implemented.

• Epinephrine was continued, but a low dose inotropy was recommended. In the acute phase, epinephrine was felt to provide necessary support for contractility and systemic blood pressure/coronary perfusion in the setting of myocardial dysfunction. Although epinephrine can increase pulmonary vascular tone, its short-term use was accepted to maintain perfusion while avoiding more aggressive escalation of other catecholamines. Ongoing reassessment was emphasized to minimize exposure once stability improved.

• Hydrocortisone was supported as adjunctive therapy. Stress-dose hydrocortisone was felt appropriate to address potential relative adrenal insufficiency and to support vascular responsiveness, thereby reducing the need for escalating catecholamine doses. Its use was not expected to directly worsen pulmonary hemodynamics and was considered beneficial in stabilizing systemic circulation.

• Dopamine was avoided. Given its dose-dependent propensity to increase pulmonary vascular resistance, dopamine was felt to risk exacerbating pulmonary hypertension without clear advantage in this physiology. In the presence of preserved pulmonary blood flow and pressure-transmitted pulmonary hypertension, dopamine was considered more likely to be harmful than helpful.

• Norepinephrine was considered but not favored. While norepinephrine could augment systemic vascular resistance and coronary perfusion, its use in the context of 100% oxygen exposure raised concern for increasing pulmonary vascular tone and afterload, potentially worsening ventricular loading and pulmonary pressures. It was therefore not selected as first-line therapy.

• Vasopressin was avoided. Although vasopressin can increase systemic blood pressure without direct chronotropic effects, concern existed that increasing afterload in the setting of left ventricular dysfunction and elevated filling pressures could further worsen left atrial pressure and pulmonary venous congestion.

• Milrinone was identified as a physiologically aligned option once systemic blood pressure allowed. Its lusitropic properties and ability to improve ventricular relaxation were felt to offer a targeted means of reducing left ventricular end-diastolic pressure and left atrial pressure, addressing a key driver of pulmonary venous hypertension and hemorrhage. Importantly, milrinone was favored over escalating catecholamines because it could improve ventricular performance without increasing heart rate. When initiated, discontinuation of dobutamine was recommended to avoid competing chronotropic effects.

• Inhaled tranexamic acid (TXA) was recommended as rescue adjunctive therapy during ongoing pulmonary hemorrhage. TXA was used to stabilize alveolar bleeding while avoiding the systemic and pulmonary hemodynamic perturbations associated with endotracheal epinephrine. Its role was considered supportive and temporizing, allowing time for correction of the underlying hemodynamic contributors to hemorrhage rather than serving as definitive therapy.

• Prostaglandin E1 (PGE₁) was not indicated. Given the presence of a large, already bidirectional ductus arteriosus, additional ductal manipulation was not expected to improve physiology and carried the risk of increasing pulmonary blood flow and capillary stress.

Discussion

Pulmonary hemorrhage (PH) is an acute neonatal emergency with rapid clinical deterioration and severe hypoxemic respiratory failure. Contemporary concepts emphasize “stress failure” of the immature pulmonary capillary bed, in which abrupt changes in pulmonary hemodynamics—particularly sudden reductions in pulmonary vascular resistance, venous congestion, or left-heart dysfunction—raise transmural capillary pressure and mechanical stress during lung inflation, culminating in capillary disruption and alveolar flooding. In the transitional circulation, the afterload-intolerant immature myocardium may be especially vulnerable; vasopressor-related increases in systemic vascular resistance can worsen LV performance, increase left atrial and pulmonary venous pressures, and further predispose to PH (1).

In our patient, perinatal asphyxia with acute pulmonary hypertension and a biventricular dysfunction phenotype plausibly created combined pre-capillary (PPHN) and post-capillary (pulmonary venous hypertension) physiology, increasing susceptibility to PH. Management aligned with recommended priorities: stabilization of oxygenation and hemodynamics while avoiding excessive ventilatory pressures that may exacerbate capillary leak; escalation to HFOV can be lung-protective and may tamponade alveolar bleeding. The review supports increasing PEEP/mean airway pressure judiciously, administering additional surfactant after bleeding stabilizes (given inactivation by intra-alveolar blood), and correcting coagulopathy/volume loss with blood products. Serial echocardiography is central to guide therapy in PH complicated by pulmonary hypertension and ventricular dysfunction, including careful consideration of pulmonary vasodilators; iNO may abruptly increase pulmonary blood flow and capillary stress and therefore should be used cautiously and only with echocardiography confirmed pulmonary hypertension, with early weaning once resolved. Finally, adjunctive hemostatic therapies remain an evolving area. Tranexamic acid (TXA), an antifibrinolytic that inhibits plasminogen activation and stabilizes fibrin clot integrity, has been used intravenously in selected neonatal hemorrhage cases (including PH), but neonatal evidence remains limited and optimal dosing and safety are not established. In our patient, inhaled TXA was used as rescue therapy alongside HFOV, transfusion support, and echocardiography-guided hemodynamic management. Given the limited neonatal data, TXA should be regarded as an emerging adjunct rather than standard therapy, and further prospective evaluation is needed to clarify its role in PH complicated by pulmonary hypertension and LV dysfunction (2).

References

1. Sahussarungsi S, Lapointe A, Villeneuve A, Hebert A, Nouraeyan N, Lakshminrusimha S, et al. Pulmonary Hemorrhage in Premature Infants: Pathophysiology, Risk Factors and Clinical Management. Biomedicines. 2025;13(7). See Pulmonary Hemorrhage Section.

2. O'Neil ER, Schmees LR, Resendiz K, Justino H, Anders MM. Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients: An Observational Study. Crit Care Explor. 2020;2(1):e0075.