O8. Hypoxaemia and pulmonary hypertension

Pulmonary hypertension in patients with COPD results mainly from vasoconstriction of pulmonary arterioles in response to local hypoxia, usually resulting from impaired ventilation, and vasoconstrictor peptides produced by inflammatory cells.^116-119 The vasoconstriction minimises blood flow through poorly ventilated lung, reducing the mismatch of ventilation and perfusion. While this compensatory mechanism initially helps to maintain blood gas levels, the price is increased pulmonary vascular resistance, ultimately leading to right ventricular strain and failure (cor pulmonale). The vasoconstriction is reversible initially, but vascular remodelling occurs eventually and the condition becomes irreversible. In pulmonary emphysema there is also an anatomical disruption of capillaries in alveolar walls.

Right ventricular hypertrophy is seen in about 40% of patients with an FEV₁ less than 1.0 L and in 70% of those with an FEV₁ less than 0.6 L.⁷ The presence of hypercapnia is strongly associated with cor pulmonale.⁷

When pulmonary hypertension and cor pulmonale seem out of proportion with the severity of airway narrowing, the additional factors that need to be considered include:

• sleep apnoea (central and obstructive);

• polycythaemia; and

• recurrent pulmonary thromboembolism; and

• nocturnal hypoxaemia due to hypoventilation or supine gas exchange problems

The development of pulmonary hypertension and peripheral oedema is a poor prognostic sign in COPD.¹²⁰ If untreated, the five-year survival rate is about 30%. Pulmonary hypertension is difficult to detect on clinical evaluation in patients with COPD.

Chest x-rays may show enlargement of proximal pulmonary arteries, but right ventricular enlargement is difficult to detect because of hyperinflation. Right axis deviation and P pulmonale on ECG may be difficult to detect because of low voltage traces (also a result of hyperinflation). Multifocal atrial tachycardia and atrial fibrillation are common.

Echocardiography is the best non-invasive method of assessing pulmonary hypertension but image quality is reduced by hyperinflation. This can be clarified using the more invasive procedure of trans-oespohageal echocardiography. Patients with COPD may have poor quality images on transthoracic examination and transoesophageal echocardiography may be frequently needed. Echocardiography is indicated in patients with severe disease, or when symptoms seem out of proportion to the severity of airflow limitation. Estimation of pressure relies on at least some tricuspid regurgitation. Other findings include mid-systolic closure of the pulmonic valve and increased right ventricular wall thickness.

O8.1 Treatment

Treat underlying lung disease:

The logical first step is to optimise lung function and treat all potential aggravating conditions.

Oxygen therapy:

Long term, continuous (>15h/day) oxygen therapy to treat chronic hypoxaemia prolongs survival of patients with COPD, presumably by reducing pulmonary hypertension.^{18,19,120-122} (For a detailed description of oxygen therapy in COPD see Section P).

Ventilatory support:

For patients with COPD who also have sleep apnoea or hypoventilation, ventilatory support with continuous positive airway pressure (CPAP) or non- invasive positive pressure ventilation (NIPPV) may be more appropriate than oxygen therapy (for more details see Section X). The effectiveness of NIPPV for chronic respiratory failure due to COPD remains unproven. A systematic review comparing NIPPV to a range of other interventions including spontaneous breathing and sham ventilation, identified six RCTs and nine non-RCTs¹²⁶. The RCTs found no significant improvement in outcomes for NIPPV. Arterial blood gases were no different; weighted mean difference for PaO2 was 1.86mmHg (95% CI -0.60 to 4.32) and for PaCO2 was -1.20mmHg (95% CI -5.05 to 2.65) for NIPPV compared to control. Few studies could be compared for analyses of symptoms, HRQoL, mortality or use of health resources but no significant difference was found between interventions. The efficacy of NIPPV for long-term treatment has not yet been proven.^113,123-125 Although preliminary studies have suggested that the addition of NIPPV to long-term therapy may have some beneficial effects on CO2 retention and shortness of breath, based on a 12-month study¹²⁷ and a 24-month study¹²⁸ in stable COPD patients with chronic respiratory failure, its widespread use cannot be advocated as yet.¹²⁹ However, compared with long-term oxygen therapy alone, the addition of NIPPV has some beneficial effects on CO2 retention and shortness of breath.¹²⁸

Diuretics:

Diuretics may reduce right ventricular filling pressure and oedema, but excessive volume depletion must be avoided. Volume status can be monitored by measuring serum creatinine and urea levels. Diuretics may cause metabolic alkalosis resulting in suppression of ventilatory drive.

Digoxin:

Digoxin is not indicated in the treatment of cor pulmonale and may increase the risk of arrhythmia when hypoxaemia is present.⁷ It may be used to control the rate of atrial fibrillation.

Vasodilators:

Vasodilators (hydralazine, nitrates, nifedipine, verapamil, diltiazem, angiotensin-converting enzyme [ACE] inhibitors) do not produce sustained relief of pulmonary hypertension in patients with COPD.^130,131 They can worsen oxygenation (by increasing blood flow through poorly ventilated lung) and result in systemic hypotension. However, a cautious trial may be used in patients with severe or persistent pulmonary hypertension not responsive to oxygen therapy. Some vasodilators (eg, dihydropyrodine calcium antagonists) have been shown to reduce right ventricular pressure with minimal side effects and increased well-being, at least in the short term ^132,133 Nitric oxide worsens V/Q mismatching and is therefore contraindicated in patients with COPD.^130,131