Chapter 58: Pulmonary Hypertension

Normally, the pulmonary vascular system is a high-flow, low-resistance circuit, with a mean pulmonary arterial pressure that constitutes approximately 15% to 20% of the systemic circulation.¹ Normal pulmonary arterial systolic pressures range from 15 to 30 mm Hg, whereas diastolic pulmonary arterial pressures range from 4 to 12 mm Hg.¹ Pulmonary hypertension is defined as a mean pulmonary arterial pressure >25 mm Hg at rest or >30 mm Hg during exertion.^1,2

Pulmonary hypertension is classified based on measurements of pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance. Patients with pulmonary arterial hypertension have a mean pulmonary arterial pressure >25 mm Hg, a pulmonary vascular resistance >240 dynes/s/cm⁵, and a PCWP <15 mm Hg.² In contrast, patients with pulmonary hypertension caused by left heart disease, the most common cause of pulmonary hypertension, have a PCWP >15 mm Hg.² Although echocardiography can estimate pulmonary arterial pressure in a patient with suspected pulmonary hypertension, definitive diagnosis requires right heart catheterization.

The World Health Organization classifies pulmonary hypertension into five categories based on cause and response to treatment (Table 58-1).^1,3 Some patients have features of multiple categories, but the majority have one predominant type of pulmonary hypertension.⁴ Accurate classification of pulmonary hypertension is key to directing treatments, which vary among the categories. Pulmonary venous hypertension is the most common cause of pulmonary hypertension, affecting almost 4 million patients in the United States.⁴ In contrast, pulmonary arterial hypertension is the least common cause of pulmonary hypertension, with an estimated prevalence of 15 patients per million.^4,5 Pulmonary hypertension develops in up to 4% of patients with chronic thromboembolic disease.^4,6,7 Regardless of the cause, patients with pulmonary hypertension have high morbidity and mortality rates,^4,8 with a 5-year mortality rate for patients with idiopathic pulmonary arterial hypertension exceeding 30%.⁵

The exact pathophysiology of all forms of pulmonary hypertension remains unknown. In pulmonary arterial hypertension, the initial abnormality is endothelial dysfunction, which results in an imbalance between endogenous vasodilators (e.g., prostacyclin) and vasoconstrictors (e.g., endothelin-1). The net effect is vasoconstriction and the formation of in situ thrombi. Additional pathologic processes include alterations in microvascular permeability, abnormal hypoxic vasoconstriction, microvascular thrombosis, and the formation of plexiform lesions, leading to vascular remodeling. Ultimately, these abnormalities result in sustained elevations of pulmonary vascular resistance and impairment of pulmonary blood flow.

With persistent elevations in pulmonary vascular resistance, the right ventricle (RV) dilates to maintain an adequate stroke volume. RV dilation increases the ventricular wall tension, increases oxygen consumption, and eventually decreases contractility. With progressive RV dilation, the intraventricular septum is displaced toward the left ventricle. This displacement inhibits left ventricular filling and ultimately impairs cardiac output and systemic perfusion.

Perfusion of the right coronary artery (RCA) depends on the gradient between the aorta and RV. Normally, the RCA is perfused during both systole and diastole. In patients with advanced pulmonary hypertension, RCA perfusion occurs almost exclusively during diastole.^9,10 Decreased perfusion results in right ventricular ischemia and further impairment of left ventricular output. Eventually, this cycle results in right ventricular failure and cardiovascular collapse.

The most common symptom of pulmonary hypertension is dyspnea, either at rest or with exertion, which is present in over 50% of patients.^1,11 Other symptoms include fatigue, chest pain, near syncope, syncope, and exertional lightheadedness.^3,11,12 Since these initial symptoms are nonspecific, it is not surprising that delays in diagnosis are common, with an average interval between symptom onset and diagnosis of pulmonary hypertension of 2 years.¹³ As pulmonary arterial pressure increases, patients can develop early satiety, anorexia, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema.

The physical examination is often normal in the early stages of pulmonary hypertension.¹ As pulmonary hypertension worsens, findings of right ventricular failure emerge (e.g., a holosystolic tricuspid regurgitation murmur, jugular venous distention, hepatomegaly, ascites, and lower extremity edema).^1,4 Additional findings include an increased intensity of the pulmonary component of the second heart sound (P₂), a parasternal heave, and a subxiphoid thrust in patients with right ventricular hypertrophy.^1,4

ELECTROCARDIOGRAM

The most common ECG abnormality seen in pulmonary hypertension patients is right axis deviation.¹² Additional findings associated with pulmonary hypertension include an R/S ratio >1 in lead V₁, an R/S ratio <1 in leads V₅ and V₆, a qR complex in lead V₁, an S₁Q₃T₃, right atrial enlargement in the inferior leads, and an incomplete or complete right bundle branch block¹⁴ (Figure 58-1). These findings are neither sensitive nor specific for the identification of pulmonary hypertension.

The ECG may show signs of right ventricular ischemia or dysrhythmia. The most common dysrhythmias in patients with pulmonary hypertension are atrial fibrillation, atrial flutter, and atrioventricular nodal reentrant tachycardia.^15,16 Of these, atrial fibrillation is associated with the highest mortality rate.¹⁵

LABORATORY TESTING

Routine laboratory testing (e.g., CBC, comprehensive metabolic panel) is often nonspecific in the initial evaluation of the pulmonary hypertension patient with dyspnea. B-type natriuretic peptide and N-terminal B-type natriuretic peptide are often elevated and correlate with outcomes in patients with pulmonary hypertension but have limited impact in ED care.^17,18,19 Elevations in troponin from myocardial ischemia or a strain-induced leak can be seen and are associated with higher morbidity and mortality.^20,21

IMAGING

Common chest radiographic abnormalities associated with pulmonary hypertension include enlargement of the right atrium, RV, and hilar pulmonary arteries.^12,22 Depending on the cause of the pulmonary hypertension, additional radiographic findings might include pulmonary edema, hyperinflation, or interstitial lung disease. In most patients presenting with dyspnea, a chest radiograph is obtained to identify other causes of dyspnea, such as pneumonia or pneumothorax.

Transthoracic echocardiography is the best initial diagnostic test to assess pulmonary hypertension in the ED. It allows estimation of the pulmonary artery systolic pressure⁴ and detection of decreased RV function, right atrial hypertrophy, and right ventricular hypertrophy, each of which is indicative of more severe disease.¹ Additional echocardiographic findings in patients with severe pulmonary hypertension include leftward deviation of the intraventricular septum and a right ventricle-to-left ventricle end-diastolic diameter >1 in the four-chamber view.^1,23 Figures 58-2, 58-3, and 58-4 demonstrate typical echocardiographic findings in patients with pulmonary hypertension.

Echocardiography can also detect precipitating factors for right ventricular failure, including pericardial effusion, regional wall motion abnormalities of the RV or left ventricle, and acute valvular abnormalities.²⁴

No consensus guidelines exist for the management of critically ill patients with pulmonary hypertension in the ED. The mainstays of ED therapy include supplemental oxygen, optimizing intravascular volume, augmenting right ventricular function, maintaining coronary artery perfusion, and decreasing right ventricular afterload (Table 58-2).²⁵

OXYGEN AND MECHANICAL VENTILATION

While the optimal oxygen saturation is unknown, consensus opinion is to titrate supplemental oxygen to maintain a level >90%.²⁵ Although intubation and mechanical ventilation are common ED therapies for the patient with acute respiratory failure, be wary of the complications. In patients with severe pulmonary hypertension, intubation and ventilation can cause rapid cardiovascular collapse due to increased intrathoracic pressure from positive-pressure ventilation and effects of sedative medications on right ventricular function and systemic vascular resistance.

When mechanical ventilation is needed, set the ventilator to maintain low airway pressure,²⁵ using lung-protective settings (i.e., a tidal volume of 6 mL/kg of ideal body weight and the lowest positive end-expiratory pressure to maintain the oxygen saturation above 90%). Monitor serial plateau pressure measurements and target pressures to <30 cm H₂O. Adjust the respiratory rate to avoid hypercapnia, which can increase pulmonary vascular resistance, pulmonary artery pressure, and RV strain.²⁶

INTRAVASCULAR VOLUME

Volume overload can cause RV dilation, displacing the intraventricular septum, impairing left ventricular output, and ultimately compromising tissue perfusion.³ For patients who are hypovolemic, give serial boluses of an isotonic crystalloid solution in 250- to 500-mL aliquots with close monitoring. As a result of baseline elevations in right-sided pressures, common methods used to monitor volume responsiveness, such as absolute values of central venous pressure and respiratory variation of the inferior vena cava with US, are less reliable in the patient with pulmonary hypertension.

RIGHT VENTRICULAR FUNCTION

For RV failure, start an inotropic medication to augment function and improve cardiac output. Dobutamine is preferred,^25,27,28 starting at 2 micrograms/kg/min and titrated to 10 micrograms/kg/min. Avoid doses >10 micrograms/kg/min, because large doses can increase pulmonary vascular resistance and cause tachydysrhythmias and hypotension.^29,30 For patients unable to tolerate dobutamine, milrinone is an alternative. Milrinone is a phosphodiesterase-3 inhibitor and can indirectly augment right ventricular function through a reduction in pulmonary vascular resistance.²⁵ Start milrinone at 0.375 micrograms/kg/min and titrate to a maximum of 0.75 micrograms/kg/min. Higher doses of milrinone can cause hypotension.

RIGHT CORONARY ARTERY PERFUSION

Adequate perfusion of the RCA is necessary to maintain right ventricular function and cardiac output. To maintain RCA blood flow, arterial pressure at the aortic root must be higher than the pulmonary artery pressure. For the hypotensive pulmonary hypertension patient, use a vasopressor to increase aortic root pressure and maintain RCA perfusion. Although there are limited data regarding a singular superior agent, norepinephrine is recommended.²⁵ Norepinephrine improves cardiac output and is initiated at a dose of 0.05 micrograms/kg/min. Avoid high doses of norepinephrine because it can increase pulmonary vascular resistance and impair right ventricular output. Avoid dopamine and phenylephrine because these drugs can cause tachydysrhythmias and can elevate pulmonary artery pressure and pulmonary vascular resistance.

RIGHT VENTRICULAR AFTERLOAD

Reducing right ventricular afterload with pulmonary vasodilators is a critical component in the management of stable patients with pulmonary hypertension. The most commonly used pulmonary vasodilators are prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 (PDE-5) inhibitors. These medications are used primarily in the treatment of patients with pulmonary arterial hypertension; they are rarely, if ever, administered in the ED, but understanding the therapeutic agents is important. Prostanoids (epoprostenol, treprostinil, and iloprost) are potent vasodilators and are the initial treatment of choice in patients with pulmonary arterial hypertension and right ventricular failure. These medications have antiplatelet and antiproliferative properties.¹ Epoprostenol is the only therapy proven to improve survival.²⁵ It has a half-life of just 2 to 5 minutes and must be given by continuous IV infusion.^31,32 In contrast, treprostinil has a half-life of 4 to 5 hours and is approved for both IV and SC administration.

For the acutely ill pulmonary hypertension patient receiving ongoing IV prostanoid, the first step is to confirm catheter and pump function. If occlusion or malfunction is detected, consult with the primary provider. Both epoprostenol and treprostinil can be administered by peripheral IV. Iloprost is given as an aerosol and is usually reserved for patients unable to tolerate a parenteral prostanoid.²⁵ Side effects of prostanoids include headache, nausea, vomiting, flushing, diarrhea, and jaw pain.¹

Endothelin receptor antagonists are administered orally and increase exercise capacity, improve hemodynamics, and can delay the time to clinical worsening in pulmonary hypertension patients.^{1,33,34,35,36,37} Currently, bosentan and ambrisentan are the only available endothelin receptor antagonists, but neither drug has been evaluated in the acutely decompensating pulmonary hypertension patient with right ventricular failure.²⁵ Side effects of these medications include an elevation in liver transaminase levels and a decrease in hemoglobin concentration.¹

The PDE-5 inhibitors sildenafil and tadalafil are approved for use in patients with pulmonary hypertension. They are administered orally, seeking to improve hemodynamics and exercise capacity in patients with pulmonary arterial hypertension.^{1,38,39,40,41,42,43} Like the endothelin receptor antagonists, they are not currently used in acutely ill pulmonary hypertension patients. Side effects of the PDE-5 inhibitors include headache, flushing, dyspepsia, and hypotension when used concomitantly with nitrates.¹

When patients with pulmonary hypertension present to an ED, they are often critically ill, with signs and symptoms of acute right heart failure. As a result, nearly all require admission, often to an intensive care or coronary care unit with expertise in pulmonary hypertension. On rare occasions, a mildly symptomatic patient may be discharged home after consultation, care plan development, and close follow-up with the primary provider.

No consensus guidelines exist for the evaluation and management of critically ill ED patients with pulmonary hypertension. Current recommendations are based on expert opinion.

Acknowledgment: The author gratefully acknowledges the contributions of David M. Cline and Alberto J. Machado to this chapter in the previous edition.