Respiratory failure: underlying causes and blood gas abnormalities

Causes

These diseases can be grouped according to the primary abnormality and the individual components of the respiratory system, as follows:

• Central nervous system disorders

  • A variety of pharmacological, structural, and metabolic disorders of the CNS are characterized by depression of the neural drive to breathe.

  • This may lead to acute or chronic hypoventilation and hypercapnia.

  • Examples include tumors or vascular abnormalities involving the brain stem, an overdose of a narcotic or sedative, and metabolic disorders such as myxedema or chronic metabolic alkalosis.

• Disorders of the peripheral nervous system, respiratory muscles, and chest wall

  • These disorders lead to an inability to maintain a level of minute ventilation appropriate for the rate of carbon dioxide production.

  • Concomitant hypoxemia and hypercapnia occur.

  • Examples include Guillain-Barré syndrome, muscular dystrophy, myasthenia gravis, severe kyphoscoliosis, and morbid obesity.

• Abnormalities of the airways

  • Severe airway obstruction is a common cause of acute and chronic hypercapnia.

  • Examples of upper airway disorders are acute epiglottitis and tumors involving the trachea; lower airway disorders include COPD, asthma, and cystic fibrosis.

• Abnormalities of the alveoli

  • The diseases are characterized by diffuse alveolar filling, frequently resulting in hypoxemic respiratory failure, although hypercapnia may complicate the clinical picture.

  • Common examples are cardiogenic and noncardiogenic pulmonary edema, aspiration pneumonia, or extensive pulmonary hemorrhage. These disorders are associated with intrapulmonary shunt and an increased work of breathing.

Management

Prompt diagnosis and management of the underlying cause is crucial to the management of patients with respiratory failure. Occasionally, rapid reversal of the precipitating event-e.g. tracheostomy for laryngeal obstruction, fixation of ribs in a flail chest injury, reversal of narcotic poisons, nebulised bronchodilators in acute severe asthma or tube drainage of a tension pneumothorax-will restore good gas exchange. In acute left ventricular failure, in massive pulmonary embolism and when pulmonary infarction or pneumonia is the cause of pleural pain, treatment with opiates is entirely appropriate, but these drugs depress respiratory drive and should never be used in asthma or COPD, except immediately prior to and during assisted mechanical ventilation.

Common to all cases is the need to restore adequate arterial oxygen levels, for which oxygen therapy with or without mechanically assisted ventilation is important. The consequences of untreated severe hypoxaemia include systemic hypotension, pulmonary hypertension, polycythaemia, tachycardia, and cerebral dysfunction ranging from confusion to coma.

Oxygen therapy

The delivery of oxygen to tissue mitochondria depends on several factors including: inspired oxygen concentration (FiO2); alveolar ventilation; ventilation-perfusion distribution within the lung; haemoglobin and concentrations of agents such as carbon monoxide which may bind to haemoglobin; influences on the oxygen-haemoglobin dissociation curve; cardiac output; and distribution of capillary blood flow within the tissues.

Oxygen therapy improves hypoxaemia by increasing alveolar PO2 in poorly ventilated lung units. However, in conditions where desaturated blood is completely bypassing aerated lung (e.g. a right to left cardiac shunt, or a completely consolidated lobe), increasing FiO2 has little or no effect on arterial PO2. Indeed, when a shunt is present, careful measurement of arterial PO2 when breathing 100% oxygen allows calculation of the percentage of the cardiac output flowing through the shunt.

Normally, high-flow oxygen (35-60%) is appropriate treatment in respiratory failure (e.g. severe asthma, pulmonary oedema or pneumonia) because respiratory drive is high. A small percentage of patients with severe chronic COPD and type II respiratory failure develop abnormal tolerance of raised CO2 and may become dependent on hypoxic drive to breathe. In these patients only, lower concentrations of oxygen (24-28%) may be needed to avoid precipitating worsening respiratory depression (see below).

Toxic effects of oxygen

100% oxygen is both irritant and toxic if inhaled for more than a few hours. Premature infants develop retrolental fibroplasia and blindness if exposed to excessive concentrations. In adults, pulmonary oxygen toxicity (manifested by pulmonary oedema and free radical damage leading ultimately to fibrosis) would not be expected to occur unless the patient had been treated with inappropriately high concentrations of oxygen for more than 24 hours.

Administration of oxygen

Oxygen should always be prescribed in writing with clearly specified flow rates or concentrations.

•High concentrations, such as 40-60% oxygen via a high-flow mask, are particularly useful in acute type I respiratory failure such as commonly occurs in pneumonia, asthma or pulmonary oedema. When high-flow masks are used for prolonged periods, the oxygen should be humidified by passing it over warm water.

•Low concentrations. Venturi masks (24% or 28%), are the most accurate method of delivering controlled oxygen therapy in type II respiratory failure. However, once patients are stable, if a low concentration of oxygen is required continuously for more than a few hours, 1-2 litres per minute delivered via nasal cannulae allows patients to eat and to undergo physiotherapy etc. while continuing to receive oxygen. It is important to realise that the actual percentage of oxygen received from nasal cannulae will vary widely depending on minute ventilation, nasal blockage and any tendency to mouth-breathe. Humidification is not necessary with low-flow masks or nasal cannulae, as a high proportion of atmospheric air is mixed with oxygen.

Monitoring of response to therapy

In patients with acute respiratory failure, close monitoring is essential and arterial blood gases taken on presentation should be repeated within 20 minutes to establish that treatment has achieved acceptable PaO2 levels. If hypoxia persists despite appropriate oxygen therapy, progressive hypercapnia (PaCO2 > 6.6 kPa (50 mmHg)) with acute respiratory acidosis develops or the patient becomes exhausted, an early decision should be made about whether it is appropriate to support ventilation temporarily by means of non-invasive ventilation or formal intubation and mechanical ventilation. Very ill patients may require immediate ventilatory support on presentation.

CHRONIC AND 'ACUTE ON CHRONIC' TYPE II RESPIRATORY FAILURE

The most common cause of chronic type II respiratory failure is COPD. Here CO2 retention may occur on a chronic basis, the acidaemia being corrected by renal retention of bicarbonate, which results in the plasma pH remaining within the normal range. This 'compensated' pattern, which is also seen in some patients with chronic neuromuscular disease or kyphoscoliosis, is maintained until there is a further pulmonary insult, such as an exacerbation of COPD which precipitates an episode of 'acute on chronic' respiratory failure.

ASSESSMENT AND MANAGEMENT OF 'ACUTE ON CHRONIC' TYPE II RESPIRATORY FAILURE

Initial assessment

N.B. Patient may not appear distressed despite being critically ill Conscious level (response to commands, ability to cough) CO2 retention (warm periphery, bounding pulses, flapping tremor) Airways obstruction (wheeze, prolonged expiration, hyperinflation, intercostal indrawing, pursed lips) Cor pulmonale (peripheral oedema, raised JVP, hepatomegaly, ascites) Background functional status and quality of life Signs of precipitating cause

Investigations

Arterial blood gases (severity of hypoxaemia, hypercapnia, acidaemia, bicarbonate) Chest X-ray

Management

Maintenance of airway Treatment of specific precipitating cause Frequent physiotherapy ± pharyngeal suction Nebulised bronchodilators Controlled oxygen therapy Start with 24% controlled-flow mask Aim for a PaO2 > 7 kPa (52 mmHg) (a PaO2 < 5 (37 mmHg) is dangerous) Antibiotics Diuretics

Progress

If PaCO2 continues to rise or patient cannot achieve a safe PaO2 without severe hypercapnia and acidaemia, respiratory stimulants (e.g. doxapram) or mechanical ventilatory support may be required

The further acute increase in PaCO2 results in acidaemia and worsening hypercapnia, and may lead to drowsiness and eventually to coma. The principal aim of treatment in acute on chronic type II respiratory failure is to achieve a safe PaO2 (> 7.0 kPa (52 mmHg)) without increasing PaCO2 and acidosis, while identifying and treating the precipitating condition. These patients usually have severe pre-existing lung disease, and only a small insult may be required to tip the balance towards severe respiratory failure. Moreover, in contrast to acute severe asthma, a patient with 'acute on chronic' type II respiratory failure due to COPD may not feel overtly distressed despite being critically ill with severe hypoxaemia, hypercapnia and acidaemia.

Management

In the initial assessment it is important to evaluate the patient's conscious level, the ability to cough effectively and the accompanying respiratory drive. This may give a preliminary indication of whether the patient will be able to tolerate non-invasive ventilation and whether physiotherapy will be helpful to clear retained secretions. Initial treatment includes low-concentration controlled oxygen therapy (24-28% oxygen with careful monitoring of blood gases), physiotherapy, bronchodilators, broad-spectrum antibiotics and diuretics. The risks of worsening hypercapnia and coma must be balanced against those of severe hypoxaemia, which include potentially fatal arrhythmias or severe cerebral complications. The aim of oxygen therapy in this patient group is not necessarily to achieve a normal PaO2; even a small increase will often have a greatly beneficial effect on tissue oxygen delivery since the PaO2 values of these patients are often on the steep part of the oxygen saturation curve. It is important to remember that while physical signs of CO2 retention (confusion, flapping tremor, bounding pulses etc.) can be helpful if present, they are often unreliable, so there is no substitute for arterial blood gases in the assessment of initial severity and response to treatment. If controlled oxygen treatment causes a further increase in the PaCO2 associated with a reduction in pH, non-invasive or invasive ventilatory support may be required. In this patient group the decision regarding intubation for mechanical ventilation can be particularly complex and difficult. Ideally, an early decision should be made, based mainly on whether there is a potentially remediable precipitating condition and whether the patient is likely to regain an acceptable quality of life.

Doxapram (1.5-4 mg/min) by slow intravenous infusion should only be used as a respiratory stimulant where non-invasive ventilation is not available or is poorly tolerated, or in those with reduced respiratory drive. Even in these circumstances this agent provides only minor and transient improvements in arterial blood gas parameters.

MECHANICALLY ASSISTED VENTILATION

Patients with initially severe respiratory failure (type I or type II) or those who fail to improve despite optimal medical therapy may require mechanical ventilation. In many patients with respiratory failure, intubation and intermittent positive pressure ventilation (IPPV) with full sedation is appropriate. For specific groups of patients, however, non-invasive ventilation (NIV) has proved to be of great value in the treatment of respiratory failure. NIV is particularly effective as long-term treatment in respiratory failure due to skeletal deformity, neuromuscular disease and central alveolar hypoventilation. It is also effective in 'acute on chronic' type II respiratory failure due to an exacerbation of COPD where it reduces the need for intubation and shortens hospital stay.

LUNG TRANSPLANTATION

Lung transplantation is now an established treatment for carefully selected patients with advanced lung disease unresponsive to medical treatment. Single-lung transplantation may be used for older patients with emphysema and patients with intrapulmonary restrictive disorders such as lung fibrosis. It is contraindicated in patients with chronic bilateral pulmonary infection, such as cystic fibrosis and bronchiectasis, where bilateral lung transplantation is the favoured option. Combined transplantation of the heart and lungs remains necessary for the treatment of patients with advanced congenital heart disease such as Eisenmenger's syndrome and is preferred by some surgeons for the treatment of primary pulmonary hypertension unresponsive to prostanoid therapy. Although prognosis is good with modern immunosuppressive drugs, the availability of lung transplants remains limited due to shortage of donor lungs. More recently, living lobar transplantation has been introduced.