Lung Resection and Pulmonary Hypertension

Leila Hosseinian, Benjamin S. Salter

Abstract

Patients with pulmonary hypertension (PH) undergoing thoracic surgery have a higher morbidity and mortality compared with other procedures. However, when a specialized and focused multidisciplinary care team performs their assessment, optimization, intraoperative management and postoperative monitoring, their procedures can be safely performed.

Keywords

pulmonary hypertension; lung resection; preoperative workup; right ventricular dysfunction; pulmonary vasodilators

Introduction

Pulmonary hypertension (PH) has become an increasingly common diagnosis among patients presenting for surgery. With advances pertaining to the diagnosis and treatment of PH, these patients are now living longer with an improved quality of life. Although surgery still poses a significant risk, patients with PH can safely undergo noncardiac surgery. Patients with precapillary PH undergoing noncardiac surgery have a mortality rate ranging from 1% to 9.7% and a high perioperative morbidity rate range from 24% to 42% despite improvements in the quality of treatment and optimization.^1–5 Common complications include respiratory failure (7%–28%), congestive heart failure and/or volume overload (10%–13.5%), arrhythmia (12%), hemodynamic instability (8%), acute kidney injury (7%–10%), and myocardial ischemia (4%).¹^,⁴^,⁵ Emergency procedures, particularly those with the potential for rapid blood loss, thoracic surgery, and laparoscopic surgery are all associated with highest risk.¹ Changes in intrathoracic pressure, oxygenation, airway pressure, and the need for one-lung ventilation (OLV), all can acutely increase pulmonary vascular resistance (PVR) and suppress right ventricular (RV) function, which poses an increased risk to patients with PH patients undergoing thoracic surgery. However, with diligent preoperative optimization and careful intraoperative management, lung resections on patients with PH have been performed with no increase in morbidity or mortality.⁶ Successful intraoperative management of thoracic surgical patients with PH requires a thorough understanding of the disease process, assessment of the severity of the disease and comorbidities. Proper optimization, understanding the nature of the procedure being performed and a team approach to unified anesthetic plan considering the increased risk of cardiac and pulmonary complications is essential.

Definition

PH is defined as a persistent elevation of mean pulmonary artery pressure (MPAP) 25 mm Hg or more at rest measured by right heart catheterization. This definition was established at the World Symposium on PH organized by the World Health Organization. During the sixth World Symposium on PH in 2018, experts reconsidered MPAP of 20 mm Hg as the new cut off.⁷ PH is divided into five different groups (Table 36.1) and can further be divided into three different categories based on the hemodynamic implications of the disease process (Table 36.2). Anesthesiologists need to be aware of these classifications as they impact the available treatment and management strategies.

Table 36.1

Classification of Pulmonary Hypertension
Pulmonary Hypertension
World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension	WHO Group 2 Pulmonary Hypertension Caused by Left-Sided Heart Disease	WHO Group 3 Pulmonary Hypertension Caused by Lung Disease or Hypoxia	WHO Group 4 Chronic Thromboembolic Pulmonary Hypertension and Other Pulmonary Artery Obstructions	WHO Group 5 Pulmonary Hypertension With Multifactorial Mechanisms
• Idiopathic • Heritable • Drug and toxin induced Associated with: • Connective tissue disease • HIV infection • Portal hypertension • Congenital heart disease • Schistosomiasis • WHO Group I (pulmonary venoocclusive disease and pulmonary capillary hemangiomatous) • WHO Group I (persistent pulmonary hypertension of the newborn)	• Left ventricular systolic dysfunction • Left ventricular diastolic dysfunction • Valvular heart disease • Specific congenital abnormalities	• Chronic obstructive pulmonary disease • Interstitial lung diseases • Other mixed restrictive or obstructive lung disease • Sleep-disordered breathing • Alveolar hypoventilation disorders • Chronic exposure to high altitude • Developmental lung diseases	• Chronic thromboembolic pulmonary hypertension • Other pulmonary artery obstructions (e.g., angiosarcoma, other intravascular tumors, arteritis, congenital stenoses, and parasites)	• Hematologic disorders (e.g., sickle cell disease) • Systemic disorders (e.g., sarcoidosis, Langerhans cell granulomatosis) • Metabolic disorders (e.g., Gaucher disease) • Others (e.g., renal disease)

From Hoeper MM, Humbert M, Souza R, Idrees M, Kawut SM, Sliwa-Hahnle K, et al. A global view of pulmonary hypertension. Lancet Respir Med. 2016;4:306–322. With permission.

Table 36.2

Hemodynamic Definitions of Pulmonary Hypertension
Definition	Characteristics	Clinical Group
Precapillary PH	MPAP >20 mm Hg PCWP ≤15 mm Hg PVR ≥3WU	1, 3, 4, and 5
Isolated postcapillary PH	MPAP >20 mm Hg PCWP >15 mm Hg PVR <3WU	2 and 5
Combined pre- and postcapillary PH	MPAP >20 mm Hg PCWP >15 mm Hg PVR ≥3WU	2 and 5

MPAP, Mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; WU, wood units.

Modified from Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53.

Classification/Pathophysiology

Group 1 pulmonary arterial hypertension (PAH) is associated with an alteration of pulmonary vasculature, including pulmonary arterial vasoconstriction smooth muscle hypertrophy, intimal and adventitial proliferation with eventual fibrosis, complex plexiform lesions, and thrombotic lesions.^8–10 Endothelial dysfunction disrupts the balance between the production of vasodilators and vasoconstrictors. There are various sources stimulating endothelial dysfunction and include free radicals, hypoxia, inflammatory mediators, acidosis, stress from left-to-right intracardiac shunts, and fibrin from thromboembolism.⁸ Eventually this results in an overexpression of vasoconstrictor and proliferative substances, such as thromboxane A2 and endothelin-1 (ET-1). ET-1 is both a potent vasoconstrictor but also stimulates smooth muscle proliferation, resulting in smooth muscle hypertrophy of the pulmonary vasculature. On the other hand, there is a downregulation of vasodilator and antiproliferative substances, such as nitric oxide (NO) and prostacyclin. Platelets also take part in the pathogenesis of PAH by occluding vessels through the production of thrombotic lesions and vasoconstrictive mediators.^8–10 These changes result in an elevation of MPAP and PVR with a normal pulmonary capillary wedge pressure (PCWP) and is known as precapillary PH (Fig. 36.1).

• Fig. 36.1 Pathogenesis of pulmonary arterial hypertension. (From Rubenfire M, Bayram M, Hector-Word Z. Pulmonary hypertension in the critical care setting: classification, pathophysiology, diagnosis, and management. *Crit Care Clin*. 2007;23:801–834.)

Group 2 comprises PH caused by left heart disease. Hemodynamically, this group has elevated MPAP and PCWP with a normal PVR and is known as postcapillary PH. The elevation of MPAP is caused by passive back pressure from an elevation in left atrial pressure. Initially, the transpulmonary gradient is low but eventually with longstanding disease, the increase in MPAP is caused by the increase in left atrial pressure which results in vascular remodeling and pulmonary arterial vasoconstriction and consequently an increase in the transpulmonary pressure gradient.¹¹ Careful consideration needs to be taken with the use of pulmonary vasodilators in this group of patients who are at risk of associated pulmonary edema from elevated pulmonary venous pressure.

Groups 3, 4, and 5 also fall under the category of precapillary PH. Group 3 represents PH secondary to lung disease. Hypoxia is the main driving factor causing pulmonary vasoconstriction. Hypoxia induces endothelial cell damage causing release of vasoconstrictors, such as ET-1, that lead to smooth muscle vasospasm and proliferation. Also there is eventually intimal thickening, medial, hypertrophy, and adventitial collagen deposition.¹⁰ Interestingly, although sleep disordered breathing is part of this group, relatively only a minority (17%) of patients with obstructive sleep apnea go on to develop PH. The likelihood however increases when the patient has associated underlying lung disease.¹² Group 4 includes patients with thromboembolic obstruction of the pulmonary arteries. They may develop partial or complete occlusion of the pulmonary arteries through the formation of mural thrombi. These patients have an abnormal mechanism of fibrinolysis or have underlying hematologic or autoimmune disorders resulting in a hypercoagulable state.⁸^,¹⁰ Interestingly, vascular remodeling also occurs in vessel regions not affected by thrombi which may be related to sheer stress.¹¹ Only a fraction of patients with acute pulmonary emboli develop chronic thromboembolic PH (CTEPH). Surgical intervention with pulmonary thromboendarterectomy is potentially curative.¹⁰ Anticoagulation is the main medical therapy for these patients. Finally, Group 5 is PH resulting from idiopathic or multifactorial mechanisms which include, sarcoidosis, splenectomy, and myeloproliferative disorders.

Preoperative Evaluation

Patients with PH presenting for thoracic surgery require an extensive preoperative workup. A team approach composed of multiple specialists including internists, pulmonologists, and cardiologists commonly care for these patients and a team discussion is imperative to ensure medical optimization before surgery. Considering the increased risk of thoracic surgery, a discussion with the thoracic surgeon preoperatively will help to design an anesthetic technique that best mitigates risk.

The goal of a thorough preoperative evaluation for patients undergoing thoracic surgery is to identify and optimize any current medical conditions and implement additional treatment strategies to decrease the patient’s perioperative risk. Intraoperative complications include, but are not limited to, those involving cardiac, neurologic, metabolic, and respiratory insults. A more thorough discussion of the preoperative assessment of patients undergoing thoracic surgery is covered in Chapter 8; however, a brief summary with attention to the supplemental testing required for patients with PH will be presented here.

No single test has the ability to precisely predict outcomes in thoracic surgery, so clinicians use the results from several different predictive tests to define the thresholds necessary for minimizing risk. These tests, creatively referred to as the “three-legged stool” of respiratory assessment, encompass lung mechanical function, pulmonary parenchymal function, and cardiopulmonary reserve.¹³ Functional tests of lung mechanics include forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), maximal voluntary ventilation (MVV), and residual volume/total lung capacity (RV/TLC) ratio; of these, the predicted postoperative FEV₁ (ppoFEV₁%) is the most validated for predicting complications. Pulmonary tissue function is commonly assessed using the results of arterial blood gases, spirometry, and plethysmography; however, the diffusion capacity of carbon monoxide (DLCO) remains the most useful measurement. Finally, a patient’s cardiopulmonary reserve is assessed using either a bicycle or treadmill to generate a maximal oxygen consumption (VO2 max) or the more simple, self-paced 6-minute walking test (6MWT).^13–15

The preoperative assessment in addition to the aforementioned “three-legged stool” of respiratory assessment, should also include an evaluation of the multisystemic sequelae of PH. Signs and symptoms are dynamic and fluctuate throughout the course of the disease, thus qualification of the severity of PH is necessary to optimize the patient and assess surgical risk. Additional tests can include a preoperative chest x-ray (CXR), electrocardiogram (ECG), echocardiogram, and often a right heart catheterization. The CXR can reveal the stigmata of PH, including enlargement of the pulmonary arteries and a boot-shaped or globular heart representing an elevated cardiac apex because of RV hypertrophy or pulmonary edema resulting from worsening heart failure¹⁶ (Fig. 36.2). The ECG can show evidence of RV hypertrophy, right-heart failure, including right axis deviation, a large R wave in V1, an increase in the P wave amplitude in lead II, a right bundle branch block, and possible diffuse repolarization abnormalities¹¹^,¹⁷ (Fig. 36.3). The echocardiogram offers clinicians a noninvasive method for diagnosing PH. Patients with chronic PH may have evidence of a pericardial effusion and signs of RV pressure overload, including hypertrophy, dilation, impaired function, tricuspid valve regurgitation, and flattening of the interventricular septum with possible left ventricular dysfunction (Fig. 36.4). In addition, estimates of pulmonary artery pressures can be made based on the presence and severity of tricuspid and pulmonic valve regurgitation. These echocardiographic findings, along with decreased tricuspid annular plane systolic excursion (TAPSE), Tei index (a myocardial performance index to express global diastolic and systolic function), peak systolic tricuspid lateral annular velocity, isovolumic contraction velocity and abnormal RV free wall strain are all predictors of a poor prognosis in patients with PH.¹⁸^,¹⁹