DEFINITION, HISTORY, AND EPIDEMIOLOGY
Pulmonary hemorrhage (PH) is the appearance of bright red blood from the trachea in association with acute pulmonary compromise and radiographic changes. Prior to the advent of exogenous surfactant, PH was described as a disorder primarily in term infants, in addition to the occasional very ill preterm infant, with sepsis, asphyxia, hypothermia, Rh disease, intrauterine growth retardation (IUGR), heart failure, or coagulopathy. The incidence was estimated at 1.3/1000 births1 and 18/1000 in very low birth weight (VLBW) infants.2 In recent decades, PH is more often a complication of extreme prematurity and is becoming more common as smaller, more immature infants are provided intensive care. PH is most often seen in extremely immature infants after surfactant administration,3,4 particularly when the ductus arteriosus is still patent.5, 6, and 7 The incidence of PH in VLBW infants in the immediate postsurfactant era was estimated between 3% (according to Braun et al2) and 5.7% (according to Tomaszewska et al3) and has progressively increased since 1998 (Figure 25-1).8 Although once viewed as almost uniformly fatal, the mortality now is closer to 50% in VLBW infants.3 PH accounted for 18% of all deaths in a large series of infants at 23 weeks’ gestation.9
Incidence of pulmonary hemorrhage (PH) by gestational age groups in the first 10 years after routine use of surfactant. (From St. John and Carlo.8)
Data from the Trial of Indomethacin Prophylaxis in Preterms (TIPP) study conducted from 1996 to 1998 in 1202 infants who weighed 500–999 g was reanalyzed in 2007 with respect to the effect of indomethacin prophylaxis on PH.7 The information from this analysis yields a wealth of information on the likely etiopathology of this much-feared complication. The original analysis of TIPP data included pink-tinged endotracheal secretions without accompanying ventilatory worsening or x-ray changes under the definition of PH. Infants receiving indomethacin prophylaxis had no significant reduction on PH compared to control infants.10 This is likely evidence that transient minor bleeding could be due to trauma such as suctioning.11 Infants in TIPP with serious PH were less mature, more likely male and products of multiple gestation, and to have received surfactant on the first day after birth.
These risk factors along with a protective trend with antenatal steroids have been observed in a number of other studies as well.12, 13, and 14 Prophylactic indomethacin reduced the incidence of symptomatic patent ductus arteriosus (PDA) by 50% and serious PH in the first week by 35% (Figure 25-2). After adjustment for other risk factors and accounting for timing of left-to-right ductal shunt, promotion of PDA closure accounted for 80% of the protective effect of indomethacin prophylaxis on PH. This effect became less prominent ...