Pulmonary Hemorrhage

Full citation: Sahussarungsi, S.; Lapointe, A.; Villeneuve, A.; Hébert, A.; Nouraeyan, N.; Lakshminrusimha, S.; Singh, Y.; Sabapathy, C.; Cavallé-Garrido, T.; Sant’Anna, G.; et al. Pulmonary Hemorrhage in Premature Infants: Pathophysiology, Risk Factors and Clinical Management. Biomedicines 2025, 13(7), 1744. https://doi.org/10.3390/biomedicines13071744

Webinar on Pulmonary Hemorrhage - August 2025

Management in Pulmonary Hemorrhage

This is largely inspired by the content of the NeoHeart 2025 session on Pulmonary Hemorrahge - Presentation by Dr Satyan Lakshminrusimha

In the management of pulmonary hemorrhage, avoid advancing the suction catheter beyond the tip of the endotracheal tube (ETT). Inserting the catheter into the trachea may disrupt or injure the tracheal mucosa, dislodge clots, or worsen active bleeding. Additionally, this maneuver causes loss of positive end-expiratory pressure (PEEP), which is critical for maintaining alveolar recruitment and providing tamponade to minimize ongoing hemorrhage. Avoid ETT removal unless absolutely necessary—such as in cases of large, obstructive clots that cannot be cleared and are compromising ventilation. Maintaining the ETT is preferable because:

• It preserves PEEP, which is essential to tamponade bleeding.

• Reintubation may be technically difficult, particularly in the context of active bleeding, poor visualization, and unstable physiology.

As a general reference, 1 mmHg ≈ 1.36 cmH₂O. Therefore, 6–8 cmH₂O of PEEP provides ~5 mmHg of intrathoracic pressure, sufficient to reduce capillary transudation and possibly limit hemorrhagic alveolar edema after surfactant admininistration and extubation.

The primary goal in acute pulmonary hemorrhage is to provide tamponade, prevent further bleeding, and reduce edema formation. Pulmonary circulation is a low-pressure, high-flow system bordered by the right and left heart. Several hemodynamic contributors may exacerbate hemorrhage risk:

• Restrictive PFO, left ventricular diastolic dysfunction, and left atrial hypertension increase pulmonary venous and capillary pressure.

• A rapid drop in pulmonary vascular resistance (PVR), especially with fragile capillary beds (e.g., in preterm infants), increases pulmonary blood flow.

• Impaired venous drainage due to elevated left atrial pressure can further predispose to capillary rupture.

• Regional disparities in PVR may cause shunting of blood to specific lung zones, leading to overperfusion and focal hemorrhage.

This is particularly relevant in RDS, where surfactant may be unevenly distributed and PEEP loss leads to heterogeneous aeration (especially after MIST/LISA), resulting in areas of high and low PVR. Zones with lower PVR and better compliance receive disproportionately high blood flow, which can overwhelm fragile vasculature and lead to hemorrhage.

Ventilation Strategies: Conventional vs. High-Frequency Modes

• Conventional ventilation: Both PIP, PEEP, and MAP are transmitted to the alveoli. These parameters influence both gas exchange and mean intrathoracic pressure.

• High-Frequency Oscillatory Ventilation (HFOV): The mean airway pressure (MAP) is the primary driver of alveolar recruitment and is well transmitted to the distal airspaces. However, the amplitude (ΔP) of oscillations attenuates progressively along the airways, and the alveoli primarily “see” the MAP.

• Jet ventilation (HFJV): In this mode, PEEP (not MAP) is the main pressure transmitted to the alveoli. Hence, it is crucial to maintain an adequately high PEEP level to preserve alveolar recruitment, even if MAP is relatively lower compared to HFOV.
  
  

High-frequency oscillatory ventilation (HFOV) has been shown to be more effective than conventional ventilation in improving oxygenation and reducing the alveolar-arterial (A–a) oxygen gradient in the setting of pulmonary hemorrhage. Its ability to maintain a constant mean airway pressure (MAP) and promote alveolar recruitment while minimizing volutrauma makes it a preferred modality during acute phases of hemorrhage. 

References: 

1. Yen TA, Wang CC, Hsieh WS, Chou HC, Chen CY, Tsao PN. Short-term outcome of pulmonary hemorrhage in very-low-birth-weight preterm infants. Pediatr Neonatol. 2013 Oct;54(5):330-4 

2. Ko SY, Chang YS, Park WS. Massive pulmonary hemorrhage in newborn infants successfully treated with high frequency oscillatory ventilation. J Korean Med Sci. Oct 1998;13(5):495-9. 

3. Bhandari V, Gagnon C, Rosenkrantz T, Hussain N. Pulmonary hemorrhage in neonates of early and late gestation. J Perinat Med. 1999;27(5):369-75

Epinephrine:

Adjunct therapies such as endotracheal (ET) epinephrine and surfactant have been used in conjunction with HFOV in several studies. Additionally, there is evidence supporting the use of conventional ventilation with higher levels of PEEP, combined with endotracheal epinephrine (0.1 mg/kg) and cocaine 4% (4 mg/kg) as alternative approaches to control bleeding and stabilize oxygenation.

• Dosing: Typically 0.5–1 mL/kg of 1:10,000 epinephrine, administered via ETT. Sometimes it needs to be diluted up to 3 mL to be administered for larger distribution. 

• Number of doses: Up to 1 to 5 doses have been reported.

• Preferred method: Administration via a catheter directed beyond the ETT tip is more effective than direct instillation into the ETT lumen.

• Evidence: A retrospective study comparing ETT epinephrine plus HFOV to HFOV alone found no significant difference in clinical outcomes, suggesting limited additive benefit in most cases.

Considerations and Risks

• There is no supporting evidence for cold saline instillation, and it is not routinely recommended.

• ETT epinephrine may be useful in tracheobronchial hemorrhage, where local vasoconstriction can transiently reduce bleeding.

• However, in the presence of venous hypertension (e.g., from elevated left atrial pressure or pulmonary venous congestion), systemic or local vasoconstriction may worsen the underlying pathology:

  • Increased systemic vascular resistance may exacerbate pulmonary capillary pressure and bleeding.

  • Reflex tachycardia can shorten diastolic filling time, potentially worsening left atrial hypertension and further contributing to pulmonary congestion.

References: 

1. Bhandari V, Gagnon C, Rosenkrantz T, Hussain N. Pulmonary hemorrhage in neonates of early and late gestation. J Perinat Med. 1999;27(5):369-75 

2. Chen YY, Wang HP, Lin SM, et al. Pulmonary hemorrhage in very low-birthweight infants: risk factors and management. Pediatr Int. Dec 2012;54(6):743-7.

Surfactant:

Management of pulmonary hemorrhage often involves high mean airway pressure (MAP)—whether via HFOV or conventional ventilation—to tamponade bleeding and maintain alveolar recruitment. Once active hemorrhage has subsided, exogenous surfactant can be administered to counteract inactivation of endogenous surfactant by blood products within the alveoli and to improve oxygenation. Timing is essential, as premature surfactant administration may exacerbate bleeding. Surfactant therapy in pulmonary hemorrhage is a double-edged sword. On one hand, it can precipitate or exacerbate bleeding, especially if administered during active hemorrhage. On the other hand, after bleeding subsides, blood components in the alveoli can inactivate endogenous surfactant, contributing to persistent hypoxemia and impaired gas exchange. In this context, exogenous surfactant can be beneficial. One randomized controlled trial and several case series have demonstrated improved oxygenation and radiographic findings with surfactant administration after the cessation of active bleeding. The recommended indication is persistent hypoxemia with parenchymal opacities, in the absence of ongoing hemorrhage. Surfactant should not be administered during active bleeding, as it may worsen the clinical course.

References:

1. Bozdağ Ş, et al Comparison of two natural surfactants for pulmonary hemorrhage in very low-birth-weight infants: a randomized controlled trial. Am J Perinatol. 2015 Feb;32(3):211-8. 

2. Pandit PB,et al Outcome following pulmonary haemorrhage in very low birthweight neonates treated with surfactant. Arch Dis Child Fetal Neonatal Ed. Jul 1999;81(1):F40-4. doi:10.1136/fn.81.1.f40 

3. Sadeh-Vered T, et al A Proposed Role of Surfactant in Platelet Function and Treatment of Pulmonary Hemorrhage in Preterm and Term Infants. Acta Haematol. 2018;140(4):215-220. 

4. Aziz A, Ohlsson A. Surfactant for pulmonary haemorrhage in neonates. Cochrane Database Syst Rev. Feb 3 2020;2(2):CD005254. doi:10.1002/14651858.CD005254.pub4 

5. Pandit PB, et al Surfactant therapy in neonates with respiratory deterioration due to pulmonary hemorrhage. Pediatrics. Jan 1995;95(1):32-6. 

6. Amizuka T, et al Surfactant therapy in neonates with respiratory failure due to haemorrhagic pulmonary oedema. Eur J Pediatr. Oct 2003;162(10):697-702. doi:10.1007/s00431-003-1276-x

Clinical Summary

• High MAP is essential in the initial management to provide tamponade.

• Surfactant should be administered only after active bleeding has stopped and hypoxemia persists due to alveolar dysfunction.

• Epinephrine via ETT may be considered a last-resort intervention for its temporary vasoconstrictive effect, particularly in airway bleeding, but with caution in cases of suspected venous hypertension or cardiac dysfunction due to potential for harm.

• Hemostatic Support and Post-Hemorrhagic Monitoring: Correction of coagulopathy and timely administration of blood products are essential components of pulmonary hemorrhage management. Infants with significant hemorrhage may require packed red blood cells, platelets, fresh frozen plasma, or cryoprecipitate based on clinical and laboratory indicators of bleeding risk.

Importantly, some infants develop post-hemorrhagic pulmonary hypertension, which can evolve rapidly in the hours to days following the bleeding event. These patients must be comprehensively assessed and closely monitored, particularly during this critical window. There is often a post-bleed reactive pulmonary vasoconstriction. 

A targeted hemodynamic evaluation should aim to:

• Identify the presence and directionality of pre- and post-tricuspid shunts .

• Assess right ventricular function, pulmonary pressures, and left atrial hypertension, if present.

• Evaluate left ventricular function. 

• Understand the evolving cardiopulmonary interactions to guide tailored therapy (e.g., vasodilators, inotropes, ventilation strategies).

Active surveillance during this period is crucial to optimize outcomes and to detect complications such as pulmonary hypertension or evolving cardiopulmonary instability. 

In the presence of a significant right-to-left interatrial shunt, patients may exhibit severe desaturation due to extra-pulmonary shunting. However, systemic oxygen delivery may still be adequate. Therefore, bedside assessments should focus not only on oxygen saturation, but also on indicators of tissue perfusion and oxygen delivery. Continuous, vigilant evaluation is essential to ensure that oxygen delivery matches metabolic demand, despite low saturations. This includes monitoring:

• Lactate levels

• Blood gases (pH, bicarbonate, pCO2)

• Clinical signs of end-organ perfusion (e.g., capillary refill, urine output, etc.)

The use of inhaled nitric oxide (iNO) in the context of post-hemorrhagic pulmonary hypertension is complex and remains controversial:

• iNO may theoretically prolong bleeding time, raising concerns when used in the immediate post-hemorrhagic period.

• If left atrial (LA) hypertension is a contributing factor, iNO may worsen pulmonary congestion and hemorrhage by increasing pulmonary blood flow toward an already overloaded left atrium.

• In extremely preterm infants, systematic early use of iNO has been associated with increased mortality in some studies and is not routinely recommended.
  
  

That said, in select cases—particularly those with acute reactive pulmonary hypertension, right ventricular (RV) failure, and diastolic RV hypertension leading to right-to-left shunting at the atrial level—some experts consider a carefully titrated trial of iNO to support RV afterload reduction. However, there are no randomized controlled trials demonstrating benefit of iNO in this specific scenario (i.e., post-pulmonary hemorrhage reactive pulmonary hypertension).

When the ductus arteriosus (PDA) is wide open and shunting right to left, this may reflect supra-systemic pulmonary hypertension. Contributing mechanisms can include:

• Acute reactive pulmonary vasoconstriction

• Reduced systemic filling pressures

• Left ventricular (LV) underfilling due to blood loss or pulmonary vascular sequestration, resulting in low LV output and promoting the right to left PDA shunting. (iNO may worsen the systemic steal in that context and worsen systemic perfusion).
  
  

These cases are hemodynamically complex and often unstable, requiring:

• Detailed functional echocardiography

• Multimodal perfusion monitoring

• Multidisciplinary collaboration (neonatology, cardiology, hemodynamics specialists)

Other References and Presenttation