Written by: John C. Klick, MD; Theodore J. Cios, MD; Anita Malhotra, MD; and Shayne M. Roberts, DO

Case Presentation

A 63-year-old woman presents to the preoperative holding area for elective laparoscopic hysterectomy with bilateral oophorectomy and lymph node dissection. She is short of breath and her lips are cyanotic. You ask whether she is OK. She hesitates, trying to catch her breath, and says, “I get like this when I overdo it.” She was diagnosed with pulmonary arterial hypertension (PAH) 1 year ago and is treated with calcium channel blockers. The surgery was postponed for further evaluation.

Pulmonary hypertension (PH) significantly increases perioperative morbidity and mortality, particularly in emergency circumstances.1 PH encompasses a multitude of clinical disease states and is defined as a mean pulmonary artery pressure (mPAP) of at least 25 mm Hg at rest, as measured by right heart catheterization (RHC).2 From a hemodynamic standpoint, PH can be classified into precapillary, postcapillary, or a combination of pre- and postcapillary hypertension.2 On the basis of World Health Organization (WHO) criteria, PH is categorized into 5 groups (Table).3 In this article, we focus on Group 1 PAH.

Table. Categorization of Pulmonary Hypertension
Group Pulmonary Hypertension Etiology
1 Pulmonary arterial hypertension (eg, heritable, idiopathic, etc)
2 Left heart disease
3 Hypoxemic lung disease
4 Chronic thromboembolic disease
5 Miscellaneous (eg, sarcoidosis, chronic renal failure, etc)
Adapted from reference 3.
Outpatient Management

Outpatient management of PH consists of consideration of home oxygen use and diuretic therapy, and advanced therapy for Group 1 PAH patients (prostacyclin agonists, calcium channel blockers, endothelin receptor antagonists, and cyclic guanosine monophosphate [cGMP]/nitric oxide pathway augmentation). Before initiating advanced therapy, all patients should undergo exercise tolerance evaluation, echocardiography, and vasoreactivity testing.5 This test consists of RHC to assess response after administering a short-acting vasodilator. Positive results occur when the mPAP decreases at least 10 mm Hg to a value less than 40 mm Hg, with no appreciable changes in systemic blood pressure. If positive, the patient may be a candidate for calcium channel blocker therapy.6

Epoprostenol (prostacyclin or PGI2) is recommended as first-line therapy for patients with severe disease (WHO functional class IV).7 It is a vasodilator that improves hemodynamics, functional capacity, and survival rates. In addition, it causes significant inhibition of platelet aggregation. Both vasodilation and platelet inhibition occur because epoprostenol activates adenylate cyclase and increases cyclic adenosine monophosphate in smooth muscle cells and platelets. For patients without severe or rapidly progressive disease (WHO functional classes II and III), it is suggested that oral agents such as endothelin receptor antagonists and phosphodiesterase 5 inhibitors be initiated first.6

For outpatients, epoprostenol is administered as a continuous infusion via a central venous catheter, under rigorous monitoring, starting with 1 to 2 ng/kg per minute and titrated upward. Adverse effects include flushing, joint pain, headaches, and diarrhea. Other prostacyclin analogs include treprostinil (IV or inhaled), selexipag (oral), and iloprost (Ventavis, Actelion Pharmaceuticals; inhaled).8

Endothelin is an endogenous vasoconstrictor, and endothelin receptor antagonists (ERAs) have been developed to treat PH. The ERAs are nonselective (bosentan [Tracleer, Actelion]; macitentan [Opsumit, Actelion]) and selective receptor A antagonists (ambrisentan). A Cochrane review from 2013 concluded that ERAs improve functional class and hemodynamics, reduce symptoms, increase exercise capacity, and prevent disease progression.9 Side effects, however, can be serious, including hepatotoxicity and teratogenicity.

Phosphodiesterase 5 inhibitors (sildenafil, tadalafil, vardenafil) prevent conversion of cGMP to GMP, thereby perpetuating the vasodilatory effects of nitric oxide in vascular smooth muscle. Different agents with different mechanisms of action also may be combined to increase efficacy of therapy. The most successful combination appears to be ambrisentan plus tadalafil.10

Preoperative Evaluation

Preoperative evaluation should include a thorough history and physical examination, review of functional capacity, home medication regimen and compliance, and evaluation of baseline oxygen requirements. Recent RHC findings and ECG and echocardiographic data are extremely useful for intraoperative planning.

Perioperative planning should be performed by a multidisciplinary team at a tertiary care center.11,12 For elective surgery, the team should ensure that the patient’s condition is optimized. Recent changes in functional status, hypoxemia, heart failure symptoms, or metabolic acidosis are an indication to postpone or cancel surgery to allow further optimization. A finding of right heart failure may be a cause for concern.12 History of syncope is a particularly ominous sign, indicating an inability to increase cardiac output during exertion.12 Other findings of increased perioperative risk include coronary artery disease, chronic kidney disease, and history of pulmonary embolism.12,13

Emergent surgical procedures lasting more than three hours, intermediate- or high-risk surgery, or procedures that can increase the risk for venous embolization all carry an increased risk for morbidity and mortality.11,14 Consideration should be taken to undergo procedures with minimal blood loss. Rapid volume shifts may be very poorly tolerated in patients with a tenuous right ventricle (RV).

Preoperative echocardiographic information can be very useful to not only risk-stratify patients but also guide optimal intraoperative therapy. Predictors of poor prognosis include severe right atrial enlargement and pericardial effusion.12,15 The RV is exquisitely sensitive to afterload changes and can better adapt to volume overload than pressure overload. Generally, the RV should be less than two-thirds the size of the left ventricle (LV) in a 4-chamber mid-esophageal view on transesophageal echocardiography, dilating as a compensatory mechanism. RV enlargement can lead to tricuspid regurgitation, further reducing cardiac output.16

Right ventricular contraction is a complex process consisting of free wall motion toward the septum and longitudinal shortening. Indexes to assess RV systolic function are used to evaluate how well the RV has compensated for the degree of PH. Fractional area of change is the most widely accepted measure of RV function.16

Values less than 35% indicate global RV dysfunction.16 Tricuspid annular plane systolic excursion (TAPSE) is a measure of longitudinal shortening with normal values of at least 17 mm. TAPSE correlates well with global RV function and has strong prognostic value in PH.12,16 Another simple prognostic measure is the LV eccentricity index. As the RV is overcome by volume overload, the intraventricular septum will shift leftward during diastole. Likewise, pressure overload will cause a leftward septal shift during systole.12 This shift can be measured by comparing the anterior–posterior dimensions of the LV with the medial–lateral dimensions, which is referred to as the eccentricity index. A value greater than 1.4 portends a poor prognosis.12

Perioperative management of patients with PH can be extremely challenging and complex. Anesthetic intervention on these patients can be risky, but appropriate workup and preoperative management will dramatically improve chances of a successful perioperative outcome.


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