Pulmonary hypertension

Pulmonary hypertension is defined as a mean pulmonary artery pressure ≥20 mm Hg. Ideally, this is measured during right heart catheterization.

Postnatal pulmonary hypertension

Newborns with diaphragmatic hernia, sepsis, meconium aspiration, or idiopathic pulmonary hypertension may exhibit substantial pulmonary vasoconstriction that reduces cross-sectional area. In utero, there is normally a very high resistance to pulmonary blood flow; this resistance falls abruptly after birth due to alveolar expansion, endothelial NO, prostacyclin, and other mediators. Preterm infants may also develop PH as lung disease progresses. Normally, RVP falls to normal within 1-2 weeks. Pulmonary vein hypertension Pulmonary venous hypertension may be caused by pulmonary vein stenosis or by congestive heart failure leading to increased end diastolic pressure –> increased LAP –> increased wedge pressure. This pathologic increases pulmonary capillary hydrostatic pressure which leads to an increase in pulmonary arteriolar vasoconstriction and elevated PVR over and above the transmitted pressure. This is generally reversible if/when venous hypertension is relieved.

Shunting lesions

Ventricular septal defects cause an increase in PA pressure both by increased flow (due to left to right ventricular level shunting) and by direct pressure transmission; during ventricular systole, the pressure from the aorta –> LV–>RV–>PA, such that systolic PA pressure is often systemic in the setting of an unrestrictive VSD. The same is true in the setting of an unrestrictive PDA. Over time, increased PBF from an ASD can lead to PH, particularly with other risk factors (e.g. prematurity). When caused by increased flow (without hydrostatic pressure transmission), the pathology is medial hypertrophy of pulmonary high resistance vessels, which is generally reversible once the stimulus is removed. Patients with direct pressure transmission (e.g. VSD or PDA) also develop intimal hyperplasia and inhibition of multiplication of smaller vessels, pathology that can also result from long-standing, unrepaired atrial shunts.

Whether or not to close a shunting lesion. Whether or not to close a defect depends on (a) whether the closure of the shunt will be acutely tolerated by the RV and (b) whether PVR will continue to increase over time, even despite shunt closure. Sometimes shunt patency from RV (or PA) to LV (or Ao) is essential to maintaining cardiac output (or may become so). Generally, if a lesion results in a large net left to right shunt, closing the shunt may be physiologically beneficial (though not always, particularly in older patients). If the shunt is right to left (due to PVR, not RVOT obstruction), it may be reasonable to treat the PVR medically when the shunt is an ASD (using agents shown to the right). For VSDs, this treatment is much less likely to be effective, as pressure and flow together creates a potent stimulus for PH. In adults, a PVR of >8 iWU is considered inoperable for shunting lesions.

Supporting the circulation in acute events. PH crisis may be precipitated by derecruiting events (e.g. suctioning) or agitation in at-risk patients. Signs include tachycardia, narrow pulse pressure, venous hypertension, hypoxemia, low EtCO2, and hypercarbia. In intubated patients, sedation, neuromuscular blockade, applied oxygen and hand ventilation lower PVR, as does iNO. Supporting RV function with inotropy (epinephrine, calcium) is critical, as is increasing SVR and avoiding vasodilators (e.g. milrinone), which may exacerbate hypotension in the setting of limited stroke volume; norepinephrine provides inotropy and venoconstriction. Unabated, hypotension preventing deterioration to circulatory collapse.

Treatment of PH depends upon the chronicity of disease and how well the patient is tolerating the physiology. The main considerations in PH physiology are optimizing RV function and lung health. Absent a right to left ‘pop-off’, LV filling (and therefore cardiac output) are dependent upon RV function.

Pulmonary HTN therapies

Inhaled nitric oxide (iNO) is a potent tool in the ICU because (1) it is a potent pulmonary vasodilator, (2) it has minmal effects on systemic vascular resistance because iNO is rapidly scavenged by erythrocytes, and (3) as an inhaled drug, it preferentially vasodilates alveoli that are well ventilated, thus improving VQ matching. It has few acute side effects, though rebound hypoxemia/PH may occur. It is also prudent to monitor for the accumulation of methemoglobin over time.

Phosphodiesterase inhibitors (sildenafil, udenafil, tedalafil) are frequently used to treat PH. They also have a vasodilatory effect on SVR. It does not require lab monitoring, but can be expensive, and frequently worsens reflux. Priapism can be dose-limiting. Also cause nasal congestion, visual/hearing disturbance in adults.

Endothelin a and b receptor antagonists (bosentan, ambrisentan, macitentan) are approved therapies for chronic PH. Must monitor LFTs monthly (less often with ambrisentan and macitentan). Also, known teratogens and not used in women of childbearing potential. May also cause edema and malaise.

Synthetic prostacyclin analogues (epoprostanol, treprostinil) are also FDA-approved PH therapies in adults. Epoprostenol (Flolan) is administered as a continuous IV infusion and has been largely replaced by treprostinil (Remodulin), which has a longer half-life and can be administered by IV or SQ infusions. Monitor for flushing and inflammation at infusion sites. Mild PH can be treated with oral prostacyclin analogs (e.g. orenitram, selexipag) which are also teratogens, cause significant GI upset (must be taken strictly with meals). Inhaled prostacyclin (treprostinil = Tyvaso) may also be used as a supplement in developmentally mature children capable of compliance with a specialized inhaler.