“pulmonary hypertension” will be used as a surrogate for elevated pulmonary vascular resistance in the absence of anatomic communications between the ventricles and/or great vessels It is now recognized that premature infants may suffer from acute pulmonary hypertension and that pulmonary vascular disease increases morbidity and mortality associated with chronic lung disease (Table 15.7) It is important to make a distinction between reversible and irreversible causes because the responsiveness to pulmonary vasodilator agents depends on the degree of pulmonary vascular remodeling Factors contributing to pulmonary remodeling include hypoplasia due to prolonged rupture of membranes or renal agenesis Table 15.7 Causes of Pulmonary Hypertension in Premature Infants Acute Reversible Respiratory distress syndrome Pneumothorax Sepsis Irreversible Pulmonary hypoplasia Congenital diaphragmatic hernia Chronic, With Variable Reversibility Chronic lung disease Chronic patency of arterial duct or other left-to-right shunt lesions Congenitally malformed heart Mild pulmonary hypoplasia Acute Pulmonary Hypertension Persistent pulmonary hypertension of the newborn is defined as the failure of normal postnatal fall in pulmonary vascular resistance to a sufficient degree to facilitate an adequate rise in pulmonary blood flow for oxygenation, regardless of absolute pulmonary artery pressure.222 The incidence is not clearly described, although a higher frequency than in term neonates has been reported.223 The regulation of pulmonary vascular resistance represents a balance between vasoconstrictor and vasodilator agents and the biochemical processes integral to transition are developmentally regulated, which may make preterm infants at greater risk.224 In addition, preterm infants are more frequently affected by lung parenchymal disease, which impacts on the adequacy of recruitment and oxygenation, both of which may modify pulmonary blood flow The clinical consequences of acute pulmonary hypertension include oxygenation failure and poor systemic blood flow, which may lead to hypotension related to right ventricular failure and/or pulmonary-to-systemic shunting.225 Early onset acute pulmonary hypertension may be associated with increased risk of chronic lung disease, particularly in those with pulmonary hypoplasia,226 and the mortality rate for preterm infants with pulmonary hypertension, at 26.2%, is six times higher than matched controls.223 Diagnosis of Pulmonary Hypertension in Premature Infants The diagnosis of pulmonary hypertension in premature infants is challenging, particularly in the presence of lung disease The signs and symptoms of pulmonary hypertension are nonspecific A gradient between preductal and postductal oxygen saturation may be helpful, if present; however, it is commonly absent in the presence of a small or absent ductus arteriosus or a bidirectional shunt at the ductal level, and therefore the absence of a gradient does not rule out acute pulmonary hypertension as a diagnosis The electrocardiogram may reveal features of pulmonary hypertension, such as tall P waves and evidence of right ventricular hypertrophy Cross-sectional echocardiography is the gold standard because cardiac catheterization is rarely performed and may be poorly tolerated The estimation of right ventricular systolic pressure from the velocity of the tricuspid regurgitant jet may underestimate the true pulmonary artery pressure in the presence of significant right ventricular dysfunction.227 Assessment of septal curvature may be used; however, the presence of a patent duct and transductal shunting allows more accurate quantification of pulmonary arterial pressure.228 Echocardiography for Identification of Complications of Pulmonary Hypertension Echocardiographic assessment of ventricular performance may be valuable, particularly on serial examinations, because the right ventricle is uniquely vulnerable to afterload and may tolerate pulmonary hypertension poorly.229,230 Similarly, there is evidence in term neonates that pulmonary hypertension is associated with left ventricular dysfunction,231 which may relate to reduced preload, abnormal conformation, ventricular-ventricular interaction, or impaired coronary oxygen delivery There are limited, but increasing, reference ranges for measures of myocardial performance in preterm neonates Treatment of Acute Pulmonary Hypertension The management of preterm neonates with acute pulmonary hypertension is based on three principles First, it is essential that modifiable factors contributing to pulmonary vasoconstriction be corrected Second, pulmonary vasodilator therapy should be considered Finally, supportive treatment of cardiovascular complications such as right ventricular dysfunction and poor systemic blood flow should be instituted Respiratory Management The primary treatment is the administration of oxygen on the basis that hypoxemia leads to worsening of the pulmonary hypertension Oxygen is a potent pulmonary vasodilator, although animal experimental models demonstrate minimal interval reduction in pulmonary vascular resistance above a partial pressure of oxygen of 50 mm Hg232; this relationship may be blunted in premature infants.233,234 Hyperoxia contributes to the development of oxygen free radicals that may be poorly scavenged235,236 and are associated with pulmonary vasoconstriction.237 There remains uncertainty and controversy regarding the most desirable saturation for premature infants There is some justification for maintaining saturations greater than 93%,238 and some randomized controlled trials suggest improved mortality at higher oxygen target saturations.239 The goal of assisted mechanical ventilation is to optimize clearance of carbon dioxide and lung recruitment Both ventilation less than functional residual capacity240 and overdistension have been associated with increased pulmonary vascular resistance241 and impaired pulmonary blood flow.242 Surfactant therapy is associated with improved compliance and may reduce pulmonary vascular resistance243; however, repeat dosing may impair alveolar oxygenation and should be considered thoughtfully (Fig 15.12)