I. DEFINITION. Pulmonary hemorrhage is defined on pathologic examination as the presence of erythrocytes in the alveoli and/or lung interstitium. In infants who survive longer than 24 hours, interstitial hemorrhage predominates. Confluent hemorrhage involving at least two lobes of the lung is termed massive pulmonary hemorrhage. Although less agreement exists about the clinical definition, pulmonary hemorrhage is typically defined as the presence of hemorrhagic fluid in the trachea accompanied by respiratory decompensation that requires increased respiratory support or intubation within 60 minutes of the appearance of fluid.

II. PATHOPHYSIOLOGY. The precise mechanisms underlying pulmonary hemorrhage remain uncertain. Pulmonary hemorrhage likely results from heterogeneous conditions that converge in a common physiologic pathway.

A. Based on studies of lung effluent demonstrating relatively low erythrocyte concentration compared to whole blood, pulmonary hemorrhage is thought to result from hemorrhagic pulmonary edema rather than direct bleeding into the lung.

B. Acute left ventricular failure, caused by hypoxia and other conditions, may lead to increased pulmonary capillary pressure and injury to the capillary endothelium. This may result in increased transudation and leak into the interstitium and ultimately, pulmonary airspace.

C. Factors that alter the integrity of the epithelial-endothelial barrier in the alveolus or that change the filtration pressure across these membranes may predispose infants to pulmonary hemorrhage.

D. Disorders of coagulation may worsen pulmonary hemorrhage but are not thought to initiate the condition.

III. EPIDEMIOLOGY. Pulmonary hemorrhage complicates the course of 3% to 5% of preterm infants ventilated for respiratory distress syndrome (RDS).
Approximately 80% of pulmonary hemorrhages in preterm infants occur within 72 hours of birth. In autopsy studies, pulmonary hemorrhage is much more prevalent.

IV. PREDISPOSING FACTORS. Pulmonary hemorrhage has been linked to many predisposing factors and conditions, including RDS, intrauterine growth restriction, intrauterine and intrapartum asphyxia, infection, congenital heart disease, oxygen toxicity, maternal blood aspiration, severe hypothermia, diffuse pulmonary emboli, and urea cycle defects accompanied by hyperammonemia. Risk factors include conditions predisposing the infant to increased left ventricular filling pressures, increased pulmonary blood flow, compromised pulmonary venous drainage, or poor cardiac contractility. The following factors have been linked to pulmonary hemorrhage: