Article

INTRODUCTION
Respiratory failure (RF) is defined as the inability of the respiratory system to oxygenate the blood to a normal level. Its presence is defined by an arterial oxygen tension (PaO2) of less 60 mmHg, when breathing air (1). Hypoxaemia is manifested clinically by central cyanosis, but this may not detected until oxygen saturation falls below 90%. Carbon dioxide retention may or may not be present in respiratory failure and the only reliable method of detection is by measurement of arterial blood gases. Physical signs which may be present include confusion, aggression or mood changes (2). RF is classified into Type I and Type II by the absence or the presence of respectively hypercapnia. Type I is the most common form and it is treated by oxygen therapy, with no risk of CO2 retention. Type II RF is characterized by a failure of ventilation. It may be caused by airway blockage, disorders of respiratory muscles or pulmonary insufficiency (i. e. chronic and acute on chronic respiratory failure) (3). This review examines the management of acute RF in patients affected by chronic obstructive pulmonary disease (COPD).

DEFINITIONS AND ETIOLOGY COPD
is characterized by cough and sputum production over an extended period. The standard definition is a productive cough and sputum production for 3 months for at least 2 years, which is not caused by other condition such as tubercolosis and bronchiectasis (4). More recently the term “chronic airflow limitation” has been proposed with the thought that limitation described more precisely the physiologic impairment than does “obstruction” (5). The criteria for the diagnosis of respiratory failure in COPD patients include hypoxemia (PaO2 < 60 mmHg), hypercapnia (PaCO2 > 50 - 70 mmHg), and respiratory acidosis (pH < 7.35) associated with worsening of the patient’s respiratory symptoms compared with baseline (6). Bronchial infection, pulmonary emboli, cardiac failure, pneumonia, pneumothorax, respiratory depression (use of sedative, or narcotic analgesic drugs), surgery (chest and upper abdomen) and stopping of medications are the causes of RF in COPD. In particular infection is thought to be an important cause of RF in COPD, but this has been difficult to prove in microbiology study or placebo-controlled trials of antibiotic treatment. The organisms most commonly implicated are viral agents and two major bacterial species, S. pneumoniae and H. influenzae. Most exacerbations ascribed to infection are thought to represent viral infection of the upper airways(7). However conclusion regarding the role of infection as a cause of acute exacerbations are inconclusive. In fact infections do not appear to promote the basic disease process and the progressive deterioration in pulmonary function (8).

PHYSIOLOGY OF COPD COPD
patients have moderate to severe increase in airway resistance with little increase in lung volume or decrease in gas transfer capacity (9). Universal in all COPD patients there is an inequality ventilation/perfusion with a tendency to hypoventilation. The pathologic abnormalities of COPD leads to an increase physiologic death space, impairment of gas exchange and the tendency of small unsupported airways to collapse. Their premature closure during expiration lead to traps air in distal space which leads to hyperinflation. Therefore patients breaths at very high volume, placing chest wall and respiratory muscles to a disadvantage (10). Arterial blood gases taken from patients suffering of COPD show a moderate - severe hypoxaemia with moderate hypercapnia. These abnormalities put the patients to high risk of cor pulmonale and other hypoxemic complications (11).

MANAGEMENT
Initial management aims to restore respiratory function to an acceptable level by using conservative methods, if at all possible, to apply immediate lifesaving measures (treat hypoxaemia and airflow obstruction), to determine and correct the precipitating factors, to treat the underlying condition, to avoid invasive techniques or mechanical ventilation with their associated risk and monitor the patients in intensive care units (12). Conservative therapies are reported in Table 1. Oxygen Therapy Oxygen therapy is the cornerstone of treatment. Death or irreversible brain damage results within minutes when hypoxaemia is present, whereas hypercapnia may be well tolerated. The appropriate amount of oxygen is that which satisfies tissues oxygen needs: usually a PaO2> 60 mmHg, without worsening the respiratory acidosis and/or further sensorium depression(13). When giving oxygen therapy to those with severe COPD and respiratory failure there is always concern about causing CO2 retention. However reversal of hypoxia is by far the most important consideration and oxygen therapy should never be withheld or withdrawn on the basis of hypercapnia. Oxygen therapy is controlled by adjusting delivery to produce an arterial saturation of 90 - 92% on pulse oximetry, and by the taking of frequent blood gases, the aim being to increase PaO2 to 60 mmHg. Hypoxic patients are operating on the steep portion of the oxygen dissociation curve and thus small changes in PaO2 will produce useful increases in arterial oxygen content. A rise in PaCO2 is common, but if over 10 mmHg oxygen delivery may need to be reduced and repeat blood taken. If no rise in PaCO2 is seen then oxygen may be increased to allow high oxygen saturation. The pH must not be allowed to fall below 7.25. The oxygen may be delivered via Venturi mask or nasal cannulae, which allow the patient to talk and eat, and may be better tolerated (14). Specific Pharmacotherapy Pharmacotheapy includes bronchodilators, corticosteroids and diuretics. Beta2 agonist such as salbutamol are routinely given and act both to dilate the airways and to improve mucociliary clearance. Steroids may be useful to improve airflow obstruction. Its use is still controversial. Albert and al. observed only modest improvement in spirometric values after 72 hours of treatment. Moreover Emerman et al. observed no better improvement in FEV1 measured by spirometry initially and after the third and the fourth aerosol treatment in COPD patients with RF receiving intravenous steroids (16, 17). However it is doubtful that steroids are harmful when given just for a few (2 - 3 ) days. Supportive Pharmacotherapy Left ventricular failure may be a factor in the deterioration of lung function due to pulmonary hypertension and the resulting pulmonary oedema. A loop diuretic such as frusemide may be indicated to improve respiratory function(18). These patients will be sensitive to fluid changes and so intravenous fluids should be administered with caution. Recently it has been reported that digoxin might improve transdiaphragmatic twitch response to phrenic nerve stimulation and increase blood flow to the diaphragm in patient with COPD (19). Therefore digoxin could be given in the treatment of CPOD patients with RF. However clinical studies should be conduct to support the use of digitalis in these patients. Acute exacerbations of COPD are often contributed to by infection and thus broad spectrum antibiotic cover is usually initiated, cefotaxime and erythromycin being common choices. This may be withdrawn or modified following microbiology results(20). Respiratory stimulants may be helpful if reversible respiratory depression is present. However in COPD patients respiratory drive is already increased and such drugs may increase respiratory distress and potentiate fatigue. They are most beneficial in sedated those who have taken respiratory depressants e.g. morphine. Naloxone is found to beneficial in these patients. Almitrine bismesylate is an oral respiratory stimulant which acts on peripheral arterial chemoreceptors. It has been found to be beneficial in exarcerbations of COPD in some studies, causing a significant increase in PaO2 and fall PaCO2 (21). However it is not standard therapy. Electrolyte imbalance may be present. Hypophosphataemia is frequent and may be secondary to respiratory acidosis. It can impair respiratory muscle function so it is recommended that those who have severely low plasma phosphate, or have pre- existing low phosphate levels or alcoholics should be given phosphate. Hypokalaemia, hypomagnesaemia and hypocalcaemia may also impair respiratory muscles and should e corrected. In those who these methods have failed and continue to deteriorate it may become necessary to begin mechanical ventilation. Before this it may be beneficial to attempt sputum clearance with more invasive techniques than those mentioned before. Broad spectrums of techniques are available, and are summarized in Table 2.

MECHANICAL VENTILATION
With failure of the all-conservative treatments and worsening of RF mechanical ventilation will become necessary. This carries substantial risks in patients who have chronic respiratory disease. They carry a greater risk of complications, are more likely to have weaning difficulties and may become dependent on ventilatory support. The most important factor in selecting suitable patients is their preaddmission level of function and quality of life. Those who are severely incapacitated with poor exercise tolerance are unlikely to be successfully weaned from ventilation. Those however who lead an active life style will be more suited and more aggressive treatment is appropriate. General criteria for mechanical ventilation are reported in table 3. Past history of ventilation, duration of time in intensive care and details of weaning should be sought. Polycythaemia and cor pulmonare suggest that hypoxia has been present for some time and thus may be less suitable for mechanical support. Those who have a reversible component to their illness have potential to improve and should be ventilated whereas those who have end stage disease are unlikely to benefit. If there is any doubt about the success or failure of treatment the patient should obviously be intubated and ventilated. Hypercapnia or acidosis alone are not indications for ventilation as these may be maintained for some time before RF occurs. Non-invasive positive pressure ventilation (NiPPV) is an option and avoids endotracheal intubation and there is some evidence that nasal intermittent positive pressure ventilation reduces mortality compared with conservative methods. However significant controversy exists concerning the exact indication for NiPPV for COPD patients with acute RF. Several randomized controlled studies support the use of NiPPV as an appropriate treatment in patients with RF (22). One study recommends that NiPPV should be initiated if arterial pH falls below 7.35 or if the patient is severely distressed (23). 10-20 cmH2O of positive pressure via a facemask is likely as the optimal technique. Larger, controlled studies are required to determine the potential benefit of adding NiPPV to standard medical treatment in order to avoid endotracheal intubation in hypoxemic RF. Mechanical ventilation should be aimed to avoid pulmonary hyperinflation. This is achieved by using low tidal volumes, low minute ventilation and long expiratory times. High inspiratory flow rate results in a longer expiratory time and tidal volumes as low as 8 ml/kg may be recommended. Minute volumes of less than 200 ml/kg are suggested and combined with low tidal volumes allow high ventilation rates (20-25/min). If pH needs to be raised higher minute ventilation may be required so pulmonary hyperinflation and its effects must be considered prior to initiating therapy (24). The risks associated with excessive hyperinflation are greater than those of hypercapnic acidosis and so the latter must be tolerated if minute volumes are becoming too large. Also patients who are chronically hypercapnic have a compensatory metabolic alkalosis. Forcing their PaCO2 down to normal levels may cause a marked increase in pH, leading to a reduction in ionized calcium, cerebral vasoconstriction and possibly fitting.

OUTCOME
Data on the outcome of COPD patients are limited. A single bout of RF does not appear to affect prognosis, but mortality increases after a second occurrence. However the prognosis remains controversial. Hospital mortality varies from 6 - 38%. And the two survival rate from 25 - 68% (25). The initial cause of acute RF in patients with COPD is important to predict mortality. In fact in patients with infection mortality has been reported to be of 20%, while in patients with heart failure is of 40%. When endotrachea1 intubation is necessary, survival after one year is usually lower than 40%. One factor affecting the data is that some patients may choose to not undergo intensive therapy treatment for respiratory failure when suffering from end stage disease(26).