A detailed discussion is given by (Derenne et...§l.i.l98.8) and Ziment.(1990).
Patients with acute respiratory failure in the setting of chronic obstructive pulmonary disease frequently exhibit severe hypoxemia, with PaO2 often decreasing below 6 kPa. Thus one of the therapeutic priorities should be to raise PaO2 by O2 therapy. However, aspects specific to this group of patients should be stressed to guide the optimal use of O2. First, chronic obstructive pulmonary disease patients are chronically hypoxemic, and therefore develop counter-regulatory mechanisms such as increased hematocrit and enhanced O2 extraction by the tissues. Hence the tolerance of these patients to acute hypoxemia is improved. Second, overzealous administration of O2 can induce considerable worsening of hypercapnia through complex mechanisms involving altered ventilation-perfusion relationships, the Haldane effect, and a decrease in minute ventilation. This acute rise in PaCO2 can result in a further lowering of pH, as well as in a clinical entity known as 'carbonarcosis', presenting as agitation, drowsiness, or coma. Third, the lower range of PaO2 discussed here corresponds to the steep portion of the hemoglobin dissociation curve. Hence even a modest gain in PaO2 entails a substantial rise in arterial O 2 saturation and content. Consequently, the main goal of O 2 therapy should be to increase PaO2 to approximately 8 kPa, which marks the end of the steep portion and the beginning of the flattened portion of the hemoglobin dissociation curve. To attain this objective, the inspired fraction of O2 (FiO2) should be carefully titrated upwards ('controlled oxygenation') by increments of 0.04 from an initial level of 0.24 or 0.28. Controlled oxygenation can be performed using nasal cannulas or Venturi masks. With the former, an increase in O 2 flow rate of 1 l/min raises FiO 2 by 0.04, provided that the patient's minute ventilation remains constant. With Venturi masks, FiO 2 is determined by the fixed relationship between O2 and room air flow rates. The O2 flow rate and resultant FiO2 are usually indicated on interchangeable color-coded adapters fitted to the mask. Arterial blood gases should be assessed every 30 min. If PaO2 remains under the target value, PaCO2 has not increased by more than 2 kPa, and the patient does not exhibit signs of carbonarcosis, FiO 2 should be increased to the next highest level. In severe cases of CO 2 retention after FiO2 has been increased, FiO2 must be lowered to the preceding level. Patients should not be returned to room air in the hope of accelerating the decrease in PaCO2, as severe hypoxemia due to increased CO2 stores will result. If it is impossible to raise PaO2 to the target levels without major CO2 retention, non-invasive ventilation or intubation should be performed.
The major benefit expected from bronchodilators is a decrease in the reversible component of bronchial obstruction, leading to improved alveolar ventilation and gas exchange, and reduced work of breathing. The most commonly used bronchodilators are adrenergic b2-receptor agonists, the anticholinergic drug ipratropium bromide, and methylxanthines.
Beta-2 agonists, such as salbutamol (albuterol) or terbutaline, can be given by oral, aerosolized, subcutaneous, or intravenous routes. There is no clear evidence that one agent is superior to the others in the acute setting. Long-acting preparations should be reserved for chronic treatment to avoid accumulation of repeated doses to toxic levels. Aerosols entail greater bronchodilatation than oral or subcutaneous routes, and should be preferred. Metered-dose inhalers or compressed air nebulizers can be used; the latter are a better choice if patient co-operation is limited. Aerosols should initially be administered every 4 h. The recommended doses for each nebulization are 1.25 to 2.5 mg for salbutamol and 2.5 to 5 mg for terbutaline. In patients incapable of performing aerosol therapy, the continuous intravenous route is preferable to subcutaneous injections because of the more rapid onset of action. A typical regimen for salbutamol is to begin the infusion at 0.07 mg/kg/min, and then to increase the rate up to a maximum of 0.3 mg/kg/min if severe obstruction persists. Side-effects of b2-agonists are usually dose dependent, and include tremor, restlessness, tachycardia, arrhythmias, hypokalemia, worsening of ventilation-perfusion ratios, and peripheral vasodilatation (usually in high-dose intravenous administration).
The bronchodilating efficacy of ipratropium bromide is possibly superior to that of b 2-agonists in some chronic obstructive pulmonary disease patients. Furthermore, combining this drug with a b2-agonist can result in an additive bronchodilator effect compared with ipratropium bromide alone. Ipratropium bromide is given by a metered-dose inhaler or a compressed air nebulizer. The usual dose for each nebulization is 0.125 mg, but up to 0.25 to 0.5 mg can be administered if obstruction is severe.
The use of aminophylline in acute on chronic respiratory failure is controversial and should best be avoided. Indeed, its bronchodilator effect is inferior to that of b2-agonists, and no benefit of combining the two agents has been demonstrated. Furthermore, even though aminophylline could increase diaphragmatic contractility in both normal humans and chronic obstructive pulmonary disease patients, there is no clear-cut evidence that it can prevent the respiratory muscle fatigue which often leads to mechanical ventilation. Finally, it has a narrow therapeutic margin with a substantial risk of arrhythmia, particularly if b 2-agonists are administered concomitantly.
Theoretical benefits derived from corticosteroids include a reduction in bronchial inflammation and hyper-responsiveness, as well as potentiation of the bronchodilating effect of b2-agonists. However, only about 20 per cent of stable chronic obstructive pulmonary disease patients are 'responders', i.e. significantly improve their forced expiratory volume at 1 s (FEVJ when receiving corticosteroids. Furthermore, published data on their efficacy in acute respiratory failure are scarce and controversial. Potential acute side-effects include gastric ulcer and bleeding, hypokalemia, sodium retention, and psychiatric disorders. Hence, we prefer to reserve these for patients who are known 'responders' and those who were taking corticosteroids prior to admission. When major bronchospasm is present, we use prednisolone at an initial dose of 1 mg/kg every 6 h during the first 2 days, tapering off over a few days to 1 mg/kg/day which is subsequently lowered according to the clinical course.
Lower respiratory tract infections which cause the majority of episodes of acute respiratory failure are not always of bacterial origin. However, the bulk of evidence suggests that empirical antibiotic treatment directed against Gram-positive and Gram-negative organisms should be initiated when worsening dyspnea is accompanied by an increase in the purulence or production of sputum. Amoxicillin (amoxycillin) plus clavulanic acid or cefuroxime are effective against the pathogens most commonly identified in these patients (Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis). However, the emergence of penicillin-resistant strains of S. pneumoniae warrants caution, and the choice of antibiotic must be guided by the geographical and epidemiological distribution of such strains and by local epidemiological data. Ceftriaxone is an alternative in this situation. When the chest radiograph suggests pneumonia, adding erythromycin in case of Legionella pneumophilia infection should be considered until sputum Gram stain and cultures are obtained.
Digitalis has no place in the treatment of cor pulmonale, and should only be used to treat acute supraventricular tachyarrhythmias such as atrial fibrillation. Heparin
Either standard or low-molecular-weight heparin should be administered to prevent deep venous thrombosis. The dose should be 5000 units two to three times daily or 2500 units once daily respectively.
Many chronic obstructive pulmonary disease patients exhibit an increased resting metabolic rate, and nearly 50 per cent of those admitted to hospital with acute respiratory failure show some degree of protein calorie malnutrition. Nutritional support should aim to meet the raised metabolic needs of the acute episode, while a thorough assessment of the patient's nutritional status should guide objectives for the long term. Care should be taken not to administer large carbohydrate loads, as they lead to increased CO2 production and O2 consumption. Initially, patients should receive approximately 30 kcal/kg/day, not more than 40 per cent of which should consist of carbohydrates. The enteral route is preferred.
Hypercapnia in decompensated chronic obstructive pulmonary disease patients results from mechanisms such as increased dead-space ventilation, respiratory muscle fatigue, and increased CO2 production in the presence of a considerable rise in the respiratory drive. Hence, agents leading to further increase in respiratory drive, such as doxapram or medroxyprogesterone, are not useful and can worsen dyspnea.
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