Pathophysiology of End-Stage Lung Disease

Depending on the specific underlying etiology, lung transplantation patients have varying degrees of impairment of gas exchange, pulmonary mechanics, and RV function. Most of the disease processes affecting the small airways or pulmonary parenchyma, such as IPF, CF, and COPD, result in some degree of ventilation-perfusion mismatch. The principal manifestation of this mismatch tends to be hypoxemia, or a low arterial partial pressure of oxygen compared with that predicted by the alveolar gas equation:

PAO₂ = (760 − P_{H2 O} × FIO₂ − (PaCO₂ /R)

where PAO₂ is the alveolar partial pressure of oxygen; PH₂ O is the alveolar partial pressure of water vapor, usually assumed to be 47 mm Hg; FIO₂ is the inspired fraction of oxygen; PaCO₂ is the arterial partial pressure of carbon dioxide; and R is the respiratory quotient, usually assumed to be 0.8.

Ventilation-perfusion mismatch only partly explains the occurrence of hypercapnia with advanced pulmonary disease, because relatively normal lung units have a limited ability to compensate for diseased units in the elimination of CO₂ . Instead, retention of carbon dioxide is largely attributed to the increased work of breathing and decreased minute ventilation inherent in the altered pulmonary mechanics that typify IPF, CF, and COPD. Arterial hypercapnia is most characteristic of lung transplantation patients with CF or COPD and less typical of those with IPF or PPH. A resting hypoxemia that is aggravated by exercise is typical of patients with COPD, IPF, or CF and less so in those with PPH. Patients with resting hypoxemia (i.e., PaO₂ <60) frequently demonstrate some degree of polycythemia. Those with an increased carbon dioxide level are likely to have respiratory acidosis with metabolic compensation that is mediated by renal retention of bicarbonate ion.

The derangement in pulmonary mechanics assumes central importance in the intraoperative management of patients with end-stage lung disease. Although the implantation of just one donor lung may create relatively

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Patients with IPF who present for lung transplantation demonstrate a restrictive ventilatory defect. This type of pulmonary pathophysiology is characterized by decreased parenchymal compliance because of inflammation and subsequent fibrosis of alveolar cells and their interstitium. Patients with normal lungs but noncompliant pleurae or respiratory muscle weakness are also said to have restrictive physiology, but this condition, in isolation, is uncommon in those presenting for lung transplantation. Expiratory function is unimpaired because of relatively preserved airway histology and normal to increased elastic recoil of the lung, but tidal volumes are small and the work of breathing is increased as a result of the large negative pleural pressures that must be generated to fill the lungs. Compensatory tachypnea may allow adequate CO₂ elimination, yet resting hypoxemia is common in those with advanced IPF. Pulmonary function tests reveal decreased lung volumes (residual volume, FRC, TLC, and FVC are all reduced), and although FEV₁ may also be reduced commensurate with the overall decrease in expiratory volumes, the FEV₁ /FVC ratio is usually preserved or increased. Diffusion of carbon monoxide (DLCO) is typically reduced.

The alteration in pulmonary vasculature may be primary, as in PPH, or may develop as a later complication of another primary lung disorder such as IPF or, less commonly, COPD. Irreversible changes at the pulmonary arteriolar level develop in those with Eisenmenger's syndrome as a result of chronic pulmonary overcirculation caused by the congenital cardiac defect. In all cases, the significance of the pulmonary vascular changes is not the impairment in gas exchange or pulmonary mechanics, but the elevation in PVR that ensues. With increasing PVR, higher pressure must be generated within the pulmonary arteries to maintain cardiac output. Initially, the right ventricle compensates for the increased workload by increasing muscle mass and chamber size. Ultimately, however, the ability to compensate is limited, and the dilated, hypertrophic right ventricle begins to fail against its increased afterload. Tricuspid regurgitation is common because of annular dilation, which adds to the RV failure. Although much of the elevation in PVR is fixed (as a result of muscularization and intimal hypertrophy of precapillary blood vessels or, in the case of COPD and IPF, destruction and paucity of alveolar capillaries), many patients will exhibit a certain degree of reversibility. This potential for reversibility explains the use of pulmonary vasodilators (e.g., calcium channel blockers or prostaglandin analogs) in many patients with PPH and also underscores the importance of paying attention to factors that may aggravate PVR while under anesthesia (see the later section "Intraoperative Management"). Variably, some patients' increased PVR may be attributed to hypoxemia and its attendant polycythemia, which acts to increase blood viscosity and causes an effective elevation in resistance across the pulmonary vascular bed.