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Approach to respiratory failure in emergency department - Eur Rev Med Pharmacol Sci 2006


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Approach to respiratory failure in emergency department - Eur Rev Med Pharmacol Sci 2006

Approach to respiratory failure in emergency department - Eur Rev Med Pharmacol Sci 2006

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  • 1. European Review for Medical and Pharmacological Sciences 2006; 10: 135-151 Approach to respiratory failure in emergency department P FORTE, M. MAZZONE, G. PORTALE, C. FALCONE, F MANCINI, . . N. GENTILONI SILVERI Department of Emergency Medicine, Catholic University – Rome (Italy) Abstract. – Objectives and Background: The goal of this review is to provide update recommendations that can be used by emergency physicians who provide primary cares to patients with Acute Respiratory Failure (ARF), from the admission to an emergency department through the first 24 to 48 hours of hospitalization. This work wants to address the diagnosis and emergency medical care of ARF and the management of medical complications. State of the Art: A lot of statement has been developed for the early management and treatment of ARF; moreover, over the last fifteen years, we have assisted to the rise of a new technique of ventilation, in the Emergency Department: Non Invasive Ventilation. This kind of ventilation was firsthy applied in Intensive Care and in Respiratory Care Unit. Randomized controlled clinical trials have showed its usefulness in the early treatment of several forms of ARF, together with medical therapy. Key Words: Respiratory failure, Pulmonary edema, Asthma, Pneumoniae, Therapy in emergency department. Introduction Acute Respiratory Failure (ARF) was defined as the inability of the respiratory system to exchange gases and to oxygenate the blood adequately1-8. We can distinguish two mechanisms at the basis of ARF: 1. Failure in pulmonary ventilation (pump failure); 2. Failure in gas exchanges (lung failure). The first one is due to neuromuscular diseases, chest wall deformities, obstructive pulmonary diseases (Table I). The second mechanism (mismatch in blood gas exchanges) is due to the following different pathologies: • Adult acute respiratory distress syndrome; • Neonatal respiratory distress syndrome; • Acute cardiogenic pulmonary oedema; • Severe status asthmaticus; • Pneumonia; • Airspace collapse (atelectasis); • Pulmonary embolism. The clinical signs and symptoms of patients with ARF, refer to the two main manifestations of pulmonary diseases: arterial hypercapnia and hypoxemia. The pathophysiology of hypercapnia is based on four main mechanisms: Increase in CO2 production (for istance, parenteral feeding with high doses of carbohydrates; high body temperature, etc.) Deterioration in gas exchanges as the increase in alveolar death space ventilation (for istance in Chronic Obstructive Pulmonary Disease – COPD –, because of mismatch in ventilation/perfusion ratio, and in pulmonary embolism); Deterioration in respiratory mechanics that involves a huge effort, an increase in respiratory work and the development of a rapid shallow breathing ↑ CO2; Alteration in the mechanism of control of the ventilation (for istance, in chronic hypercapnia, we observe a decrease in ventilatory drive with an increase in tolerance threshold to CO 2; it happens in metabolic alkalosis too). The hypoxemia is due to different pathophysiological mechanisms: • Hypoventilation; • Alteration in gas diffusion; Corresponding author:; 135
  • 2. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . Table I. Neuromuscular diseases Drugs abuse Cervical tetraplegia Curare/strychnine/ phosphate poisoning Guillaine-Barré syndrome Miastenia gravis; hereditary/ acquired myopathies Botulism/Poliomyelitis Chest wall deformities Bilateral or hypertensive Pneumothorax Pneumomediastinum Post-traumatism Obstructive diseases Severe Status Asthmaticus Central airways obstruction • Mismatch in ventilation/perfusion ratio; • Pulmonary shunt. Which are the clinical signs and symptoms of hypoxemia and hypercapnia? The first one shows with shortness of breath, tachycardia, mental confusion, changes of personality, restlessness, cyanosis, hyper/hypotension, arrhythmias and palpitations. Hypercapnia, instead, shows with sleepiness, mental confusion, cephalea, convulsions, arrhythmias, miosis, papilledema, peripheral vasodilation, hypotension and coma. The first goal of the initial diagnostic evaluation is to understand the underling causes, and so to do differential diagnosis among all pathologic conditions that showed the most important clinical symptom of this illness: dyspnoea. A – Approach to Patients with Dyspnoea Clinical Evaluation A patient with ARF usually presents with signs of respiratory distress: dyspnoea, cyanosis, tachypnea, accessory muscle use, paradoxical breathing and tachycardia. Primary care physician must apply the algorithm A-B-C-D, in order to exclude an Acute Upper Airway Obstruction (AUAO), first of all, and then he must operate as following: 1. He has to administer high flows of oxygen, to measure blood pressure, to take heart rate, respiratory rate, oxygen saturation, to make an electrocardiogram. 136 Moreover he has to take an arterial blood gas sample and a peripheral venous blood sample to evaluate CK, CKMB, T-troponine, LDH, AST, ALT and hemochrome. 2. At the same time he must evaluate the neurological state, in order to call for the resuscitator if Kelly score (Table II) is more than 3. 3. If neurological state is not compromised patient can be managed by emergency physician, entirely. Arterial blood gas (ABG) evaluation: – Hypoxemia with hypercapnia → pump failure due to neuromuscular disease or chest wall deformities; Lung failure due to COPD or acute asthmatic status. This last situation can be treated with pharmacological therapy and/or with non invasive ventilation, if indicated. Patient must undergo endotracheal intubation (ETI) if his clinical conditions deteriorate. – Hypoxemia with no hypercapnia → lung failure due to ARDS or cardiogenic pulmonary oedema or pulmonary embolism or pulmonary infection. If oxygen saturation in more than 90% continue to administer O 2 with face mask and high flows. If oxygen saturation is less than 90% consider the use of Non Invasive Ventilation (NIV), together with medical therapy. 4. Clinical evaluation must be associated with radiological evaluation (Chest XRays) and with continuous ABG evaluations (after 1 hour and after each changing in clinical conditions). Patient must undergo endotracheal intubation if his clinical conditions deteriorate. Evidence and Information Sources A comprehensive literature search was performed in order to select the latest recTable II. Kelly scale. • Awoke patient, he executes 3 complex orders • Awoke patient, he only executes simple orders • Sleepy patient, he can be awaken under verbal orders • Sleepy patient, he can be awaken under physical stimulus • Coma with no brainsteam alteration • Coma with brainsteam alteration
  • 3. Approach to respiratory failure in emergency department Table III. Infectious Neoplasm Traumatic External bodies aspiration Anaphylaxis Obstructive Sleep Apnea Syndrome (OSAS) Neurogenic diseases Viral laryngotracheitis (croup) Bacterial epiglottiditis Bacterial tracheitis Subglottic hemangioma Tracheal and endobronchial neoplasms Thyroid and mediastinal tumors Bilateral paralysis of recurrent nerve Modified by G. Garetto, La Nuova Medicina d’Urgenza, Ed. C.G. Torino11. ommendations for the early diagnosis and the therapy of the pathologies below. In developing of the present guidelines we considered the latest evidences in the management of dyspnoea, asthma, COPD, ARDS and we applied the ATS Consensus Conference indications9 and the BTS guidelines10 for the use of NIV in ARF. B – Approach to Patients with Acute Upper Airway Obstruction (AUAO) Etiology The causes of AUAO can be summarized in Table III11. Clinical Evaluation We distinguish two different types of upper airway obstruction: the extra thoracic presents inspiratory stridor, because of the collapse of upper extra thoracic airways, during the inspiration when tracheal pressure is minor than atmospheric one. The intra thoracic one that presents expiratory stridor, because the extrathoracic airways collapse during the expiration, when the intrapleural pressure is greater than atmospheric one. The stridor is the main symptom of AUAO (Table IV), and it’s often associated with cyanosis, loss of consciousness, nape’s hyperextension (especially in the epiglottiditis), trismus (especially in the peritonsillar abscess), dysphagia (severe epiglottiditis or pha- ryngeal obstruction). We usually observe asymmetries in diaphragmatic ranges, in respiratory movements, in the intercostal and supraclavicular re-entrances. If the physician suspects an epiglottiditis, he should be cautious in carrying out clinical examination: in fact he could provoke a complete obstruction stimulating with the tongue depressor. Moreover, if respiratory distress continues and the patient is stable (rapid shallow breathing, valid cough, conscious, lucid and alert patient but with no cardiovascular alterations) physician should take blood pressure and oxygen saturation, continuously, and often control ABG. If patient presents with respiratory arrest he should follow the Advanced Life Support Algorithm. In a second time physician should make differential diagnosis between epiglottiditis and viral croup. Anaphylaxis: if patients present with glottis’ oedema should be immediately intubated before developing complete obstruction of upper airways. Then they should be submitted to infusion therapy with adrenaline (1 mg in bolus repeatable), corticosteroids (hydrocortisol – methylprednisolone) at high doses, fluids. Table IV Infectious AUAO. . Supraglottic Subglottic Severe tonsillitis (> 10 years) Peritonsillar abscess (> 10 years) Retropharyngeal abscess (> 3 years) Epiglottiditis (3-7 years) Viral croup (3 months-3 years) Bacterial tracheitis 137
  • 4. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . Foreign bodies obstruction: do not introduce fingers into the oral cavity in order to take it out: it could slip down. If patient can speak the physician could remove it with a powerful blow in the interscapular zone (from one to four powerful blows). Moreover he can try with Heimlich’s manoeuvring. This one can be performed with supine patient, in case of loss of consciousness. If foreign body cannot be still removed, patient should be submitted to endoscopic removal, or to cricothyroidotomy, or to tracheostomy. C – Approach to Patients with ARF Due to Neuromuscular Diseases or Chest Wall Deformities Classification See Table V for the classification Signs and Symptoms of Hypoventilation • Rapid shallow breathing • Paradoxical breathing • Alternating breathing • Inability in carrying out a valid cough • Shortness of breathing (at the end). In patients with chest wall diseases, ARF is due to hypoventilation with an increase in respiratory work and rapid shallow breathing. Hypercapnia and hypoxemia associated with hypoventilation due to neuromuscular diseases are due to different mechanisms: • Muscular weakness; • Decrease of pulmonary and thoracic compliance; • Increase in respiratory work; • Decrease in central sensibility. Table V Infectious AUAO. . Chest wall deformities Kyphoscoliosis Obesity-Hypoventilation syndrome Fibrothorax-Thoracoplastic Ankylosing spondylitis Bilateral diaphragmatic paralysis Wandering costal flap Neuromuscular diseases 138 The clinical approach to these patients could be differentiated on the base of their conditions at the admission to the first aid. Preserved and stable vital functions: if upper airways are pervious, if there are no cardio-vascular troubles and Kelly score is “1” and patient presents only dyspnoea, deliver oxygen with facial mask and control arterial saturation and blood pressure continuously. If arterial blood sample shows an oxygen saturation more than 90% and a PaCO 2 less than 45 mmHg, evaluate ABG after 1 hour and control clinical conditions. Chest radiography should be done as soon as possible, to help the physician in differential diagnosis among neuromuscular diseases, chest wall deformities and brainstem pathologies. Preserved But Instable Vital Functions Cardio-circulatory arrest: ask for emergency team and follow the algorithm ALS for the cardiac arrest. Patient will be admitted to the Intensive Care Unit (ICU). D – Approach to Patients with ARF Due to COPD The term COPD encompasses two well defined entities: emphysema and chronic bronchitis. Emphysema is characterized by permanent and abnormal enlargement of airspace, distal to the bronchiole, associated to a destruction of alveolar wall, without evident fibrosis, and to an obstruction of distal lower airway. Bronchitis is defined only by a clinical definition as presence of cough and expectoration for more than three months per year for more than two consecutive years. The key feature that unites these diseases (bronchitis and emphysema) and the asthma (that we’re going to treat below) under the definition of COPD is the physiologic phenomenon of obstruction to forced expiratory airflow. COPD is a slowly progressive disease characterized by punctuated exacerbations two or three times a year in patients with significant obstruction. It is identified by the presence of airflow limitation that is not fully reversible and does not change markedly over several months. The disease is predominantly caused by smoking. The exacerbation, in most cases its due to infections, especially bacterial in-
  • 5. Approach to respiratory failure in emergency department fections (level II of evidence) 12 . The pathogens most often involved in COPD exacerbations are Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis13,14; less often, gram negative bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Among viruses have been identified: Rhinovirus, Influenza virus, Parainfluenza virus, Coronavirus, Respiratory Syncytial Virus, Adenovirus. The cause of exacerbation may be unidentifiable up to 30% of exacerbation15. guiding management of patients with acute exacerbation of COPD (level of hierarchy IV). Spirometry, however, is fundamental to making diagnosis of COPD because is the only accurate method of measuring the airflow obstruction in patients. It cannot contributes to the severity of COPD (level of hierarchy IV) or distinguish asthma from COPD; it is a poor predictor of disability and quality of life in COPD (level of hierarchy IV)17; it predicts prognosis of patients (level of hierarchy IV)18,19. Clinical Evaluation The diagnosis of the exacerbations is clinical and is based on three parameters: increasing in sputum production, purulent expectoration, worsening dyspnoea. There is a severity scale for exacerbations based on these findings16: type 1 (severe exacerbations) have all of the above symptoms; type 2 (moderate exacerbations) present only two of the three symptoms; type 3 (mild exacerbations) present only one of the symptoms but associated with one of the following at least: an upper respiratory tract infection in the past five days, fever, increasing in cough or wheezing, increasing in respiratory rate or in the heart rate by 20% above the baseline. Each patient ranks the importance of different symptoms individually, however breathlessness is the most significance symptom. Individual symptoms are not useful in making or excluding the diagnosis of COPD (level IV of hierarchy)15. Serological Assays Are Only of Epidemiological Value Sputum samples for microbiological tests (using Gram stain and culture) is indicated in seriously ill patients, if sputum is persistently present and purulent, or if there is a history of prior treatment failure (level of hierarchy IV). Arterial blood gas sample is necessary to assess the severity of exacerbation and for the initial management of the patient. Moreover, patients who have low PaO 2 , high PaCO 2, low pH are more likely to relapse within 14 days of initial presentation. ECG and/or Echocardiogram is useful to assess cardiac status if there are features of cor pulmonale (level of hierarchy IV). CT scan of the thorax is necessary in suspect of pulmonary embolism. It is useful (level of hierarchy IV) to investigate symptoms that seem disproportionate to the spirometric impairment, to investigate some suspect abnormalities in chest radiograph. Reversibility testing: there is a considerable variability in change in FEV1 in response to the same stimulus from day to day, so it is virtually impossible to interpret the response to an individual reversibility test unless the response is very large (an increase in FEV1 more than 400 ml). Reversibility testing is not recommended in the latest guideline produced jointly by the American Thoracic Society and the European Respiratory Society. Referral for specialist advice: these are made when clinically indicated, at all stages of disease, not only in the most severely disabled patients (level of hierarchy IV). Additional Diagnostic Tests Chest radiography: some observational studies showed substantial rate of chest radiograph abnormalities. However, chest radiography is not routinely necessary during exacerbations, neither for the diagnosis (level of hierarchy IV). It could be useful if there is the suspect of pneumonia, or pneumothorax or aspiration (such as in neuromuscolar diseases), or if patient is non-responsive to the therapy. As chest radiography can sometime reveal a parenchymatous pulmonary lesion such as tuberculosis or bronchial carcinoma, patients who have not had a radiography prior to the exacerbation should obtain one12. Spirometry: spirometric assessment, at the time of presentation, or during the course of treatment, is not useful in judging severity or Need of Hospital Management Most patients with acute exacerbation of COPD can be managed at home, but some of 139
  • 6. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . them need hospital treatment. This may be because of the following reasons: • Need for therapies that are not available at home (such as non invasive ventilation); • Severe breathlessness; • Poor/deteriorating general conditions; • Cyanosis; • Worsening peripheral oedemas; • Impaired neurological conditions, mental confusion; • Acute onset; • Significant comorbility particularly for heart diseases; • Changes in chest radiograph; • Significant alteration in arterial blood gas analysis (PaO 2 < 60 mmHg; pH < 7.35). Management The following assessment about the management in acute setting of COPD are based on the analysis of the most recent guidelines from 2001 to 200420-23. BRONCHODILATORS Bronchodilators are central in management of symptoms of acute exacerbation of COPD. However they do not modify the decline of lung function or, by inference, the prognosis of the disease (grade B). Anticholinergic drugs inhibit vagal stimulation of the bronchial tree and are associated with a reduction of the smooth muscle tone and an impairment of bronchial gland secretion. The bronchodilating effects of short acting inhaled anticholinergics last up to 8 hours after the administration (grade A). If administered with metered-dose inhaler (MDI), the recommended dose of ipratropium bromide is 2-4 puff (40-80 microg) four times daily. For more severe exacerbations, 0.5 mg each 8 hours (0.5 mg corresponds to 40 gtts of 0.25% solution). The duration of action of short acting inhaled anticholinergic agents is greater than that of beta 2 agonists (grade A)22. More recently, several studies have reported favourable effects with tiotropium a new long acting anticholinergic bronchodilator that must be inhaled once daily23,24. The duration of action of short acting anticholinergic agents is greater than that of short acting beta-agonists25 (grade of recommendation A). The combination of beta agonists and anticholinergics is more effective and better tolerated than higher doses of either agents used alone (grade of recommendation A)26-27. The bronchodilator effects of short acting beta agonists (i.e. salbutamol) disappear within 4-6 hours; so for severe exacerbations is acceptable to increase the number of administrations. Table VI (modified from “COPDX plan: Australian and New Zeland guidelines for managements of acute exacerbation of COPD”) shows the use of bronchodilators according to the severity of COPD. The duration of action of short acting inhaled anticholinergic agents is greater than that of short acting beta-agonists (salbutamol, terbutaline) (grade of recommendation A). The use of both of them is more effective and better tolerated than the use of each one alone (grade of recommendation A) 26-31 . Long-acting beta2-agonists (salmeterol and formoterol) provide bronchodialtion for 12 hours and are the first line treatment of acute severe asthma. Moreover they provide sustained relief in moderate to severe exacerbation of COPD (grade of recommendation A). Table VI. FEV1 Suggested treatment Mild COPD 60%-80% Moderate COPD 40%-59% Severe COPD < 40% Intermittent bronchodilators – salbutamol (200 µg) or ipratropium bromide (40 µg) Intermittent or regular bronchodilators – salbutamol (200-400 µg four times daily) or ipratropium bromide (40 µg four times daily) Combination bronchodilators may be considered Regular combination bronchodilators – salbutamol (200-400 µg four times daily) and ipratropium bromide (40-80 µg four times daily) Severity Modified from GOLD85 [evidence level D]. FEV = forced expiratory volume in one second. COPD = chronic obstructive pulmonary disease. 140
  • 7. Approach to respiratory failure in emergency department At the following dosage, salmeterol (50 microg twice daily) and formoterol (12 microg twice daily) improve the health related quality of life, lung function and symptoms. THEOPHYLLINE Theophylline is a non selective inhibitor of phosphodiesterase. Besides bronchodilation it increases central respiratory drive, respiratory muscle endurance, mucociliary clearance, cardiac output and dilation of pulmonary arteries. Theophyllines are rarely used because of their narrow therapeutic index and the potential side effects (grade of recommendation A). GLUCOCORTICOIDS Chronic treatment with oral glucocorticoids should not be used in COPD (grade of recommendation A) 32-41. In fact their prolonged use do not modify the long term decline of FEV1. Systemic preferable oral glucocorticoids are beneficial in the management of acute exacerbation of COPD (grade of recommendation A). Probably they improve the rate of lung function during the first 72 hours. Many recent COPD guidelines recommend the use of a short course (two weeks) of oral glucocorticoids in a dosage of 0.5 mg of prednisone or prednisolone/kg body weight. Inhaled glucocorticoids should be considered in patients with a documented response or those who have severe COPD with frequent exacerbations (grade of recommendation B). Patients with clinically significant acute bronchodilator reversibility may benefit from long term inhaled glucocorticoid therapy42-44. OXYGEN THERAPY AND VENTILATORY SUPPORT10 It’s indicated in patients with hypoxia to increase the oxygen blood saturation up to 90%. NIV has been shown to be an effective treatment for acute hypercapnic respiratory failure, particularly in patients with acute exacerbation of COPD in whom a respiratory acidosis persist despite maximum medical treatment on controlled oxygen therapy (grade of recommendation A). All the studies about the use of NIV in acute exacerbation of COPD have excluded patients deemed to warrant immediate intubation. NIV in fact should be undertaken as a therapeutic trial with a view to tracheal intubation if it fails. A decision about tracheal intubation should be taken before initiating NIV in each patient. ANTIBIOTIC THERAPY Antibiotics should be used in patients with purulent sputum and should be administered according to the stage of the disease (mild, moderate or severe) and appropriate to the bacterial agents probably involved. So in the mild stage with a suspected infection by Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis the recommended treatment is amoxicillin-clavulanic acid (or other more inhibiting beta-lactams available such as ampicillin-sulbactam and amoxicillin-sulbactam), at dosage of 875/125 mg/12 h for ten days or cefuroxime (500 mg/12 h for 10 days) with azithromycin (500 mg/day for three-five days) or clarithromicin (500 mg twice daily for 1 week). If patients have one or more risk factors add moxifloxacin/gatifloxacin/levofloxacin (respectively 400 mg/day, 400 mg/day and 500 mg/day for 7 days) and telithromycin (800 mg/day for 5 days). If patients have a moderate or severe condition intravenous treatment may sometimes be necessary. The first line therapy, if enteric bacteria or penicillin resistant streptococcus is involved are quinolones, piperacillin-tazobactam and, if there is a suspected infection by Pseudomonas aeruginosa, ceftazidime, imipenem or meropenem or cefepime. Management of Acute Asthma A recognized definition of acute asthma must be still developed, despite numerous clinical definition have been proposed in different workshops, working group, consensus conferences and national and international guidelines. The following table shows the major and minor criteria established by the American Thoracic Society in 2000, to define severe asthma45. According to consensus guideline, a severe episode is characterized by almost one of the following events: 1. Accessory muscle activity; 2. Paradoxical pulse exceeding 25 mmHg; 3. Heart rate > 110 beats per minute; 141
  • 8. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . 4. Respiratory rate > 30 breaths per minute; 5. Arterial saturation less than 90%. This clinical features are associated with a forced expiratory volume or a peak expiratory flow rate less than 50%. In fact the sine qua non of an episode of acute asthma is the reversible, non uniform increase in airway obstruction that induces diminished flow rate, hyperinflation of the lung and premature airway closure. Moreover with the increase in work of breathing and in expiratory effort the dynamic hyperinflation rises and auto-positive end expiratory pressure (PEEP) develops. Arterial blood gas examination: it typically shows hypoxemia, hypocapnia, respiratory alkalosis46-50. The more severe is the attack, the lower is the arterial oxygen saturation. However most asthmatic patients don’t develop marked hypoxemia and, also in severe attacks, it’s very infrequent that oxygen tension decrease under 50 mmHg. Respiratory acidosis follows hypercapnia. With extreme flow limitation metabolic acidosis develops. In fact, if cardiac output is compromised develops lactic acidosis because of the hypoperfusion of peripheral tissue; in addition the increased oxygen consumption by respiratory muscles also contributes. It may also be induced by aggressive administration of non selective sympathomimetics51. Managements In hospital settings for asthmatic patients the driving gas should be oxygen for acute ill patients. Moderately short-acting beta2adrenergic agonists such as salbutamol and terbutaline have rapid onset of action and provide more bronchodilation than do methylxanthines and anticholinergics, making them the first line treatment for acute illness. Adult patients with acute asthma should be given 2.5-5 mg of salbutamol or 5-10 mg of terbutaline (Grade of recommendation B23. There is evidence that additional benefit can be obtained by adding anticholinergic treatment such as ipratropium bromide 500 microg (Grade of recommendation A). Treatment should be repeated if patient is non responsive to the therapy. In near fatal asthma, the use of intravenous salbutamol (5 microg/min) and adrenaline (1 mg repeatable for three times each 15 minutes), is effective. 142 Nebulized corticosteroids have been used as a substitute of oral corticosteroids in moderate exacerbations of adult asthma; they have been shown to have an oral steroid sparing effect (Grade of recommendation A)23. Patients that are resistant or slowly responsive to beta-agonists need corticosteroids more urgently 52-56 . Methylprednisolone should be administered at dosage of 1 mg/kg of body weight during the acute attack. The US guidelines recommend 120-180 mg daily of methylprednisolone given intravenously (in three or four doses). It must be repeated for 48 hours in those admitted, followed by 60-80 mg/day until the FEV1 reach the 70% of normal. Oral prednisone (60 mg/day) can be substituted57. Methylxanthines, althought may have antinflammatory properties, are considerably less effective than the sympathomimetics and produce more significant side effects23-46. Compared to COPD, insufficient evidence exists to recommend the use of NIV for asthma patients; there is also insufficient evidence to recommend Continuous Positive Airway Pressure (CPAP) in acute asthma (Grade of recommendation C). The role of NIV is not yet clear established57 and it could delay the use of endotracheal intubation when it is necessary. E – Approach to Patients with Hypoxemic ARF a – Pulmonary Oedema The definition of “pulmonary oedema” is the overflow of fluid from the lung’s capillary to the alveolar spaces. We can distinguish two different entities of this pathology: cardiogenic pulmonary oedema and non-cardiogenic pulmonary oedema also called ARDS (Acute Respiratory Distress Syndrome), that can be distinguished by clinical signs and instrumental examinations, although they present the same clinical symptoms. The acute cardiogenic pulmonary oedema is a hydrostatic oedema due to an impaired function of left ventricle caused by coronary artery disease, myocarditis, cardiomyopathy, hypertension, congenital heart diseases. It occurs when the pulmonary capillary pressure rises to value exceeding plasma colloid-os-
  • 9. Approach to respiratory failure in emergency department motic pressure (approximately 25 mmHg). Clinical examination reveals a low flow state with wet crackles, jugular venous distention, third tone (S3 gallop), cardiomegaly. Concerning laboratory tests, ECG could shows signs of ischemia or infarction. There could be an increasing in cardiac enzymes and, at the radiography, perihilar distribution of oedema and the appearance of Kerley lines. Pulmonary capillary wedge pressure exceeds 18 mmHg. The treatment of acute pulmonary oedema is based on the use of oxygen, nitrates, diuretics and, if coexists cardiogenic shock, inotropes. Furosemide and nitrates (10 microg/min) are the first line of medical treatment and should be administered, together with morphine, if arterial systolic blood pressure exceed 100 mmHg. They promote diuresis and vasodilation and so act both on the pre-load and on the post-load of the heart, reducing cardiac work and improving the ejection fraction. If arterial systolic blood pressure is between 70 and 100 mmHg dobutamine (2-20 microg/kg/min) improves the contractility and reduces peripheral resistances avoiding arterial vasoconstriction (it acts only on beta receptors). If there are signs of cardiogenic shock, dopamine (5-15 microg/kg/ min) increases the contractility and improve the arterial blood pressure, acting both on alpha and beta peripheral receptors and, at low dosage, on dopaminergic receptors in the renal glomerule promoting diuresis. Oxygen could be administered with face masks with Venturi system or with reservoir to reach high concentration of oxygen until 100%. During the last ten years the use of NIV for treatment of acute pulmonary edema is developing with modality of CPAP. CPAP has been shown to be effective in patients with cardiogenic pulmonary oedema who remain hypoxic despite maximal medical treatment (Grade of recommendation B) 10,59-62. CPAP permits higher inspired oxygen content, increases mean airway pressure and improves ventilation recruiting collapsed areas of the lung. ARDS is defined by non cardiogenic pulmonary oedema, characterized by severe hypoxemia, new bilateral pulmonary infiltrates at radiography, without elevated left atrial pressure. The American - European Consensus Conference on ARDS defined the severity of the pathology by the ratio of PaO2/FiO2: a ratio of 300 or less defines the acute lung injury (ALI); a ratio of 200 or less defines ARDS regardless of the amount of PEEP needed to support oxygenation63. The pathogenesis is due to the lung damage, that causes an increasing in permeability of capillary endothelium and an alteration of lung alveolar-capillary barrier with overflow of fluid into the alveolar and interstitial space, without increasing in pulmonary circulatory pressure. The damage involves both the endothelial and epithelial surface; the activated endothelium participates and partly drives the neutrophil inflammatory response that contributes to edema formation and fibrosis64. The most common cause of ARDS is a severe infection and it accounts for approximately half of cases. It could present as a localized or systemic disease and the most common agents involved are gram-negative bacteria, that are often associated to multiple organ failure. The last syndrome is the major cause of death with a mortality of about 40% 65-68. Other frequent causes of ARDS are: trauma, disseminated intravascular coagulation (DIC), acute haemorrhagic pancreatitis, aspiration of gastric contents, inhalation of foreign bodies, acute radiation pneumonitis, inhalation of toxic gases (smoke, ozone, cadmion, chlorine, nitrogen dioxide) or circulating foreign substances (alloxan, alpha-naphthyl thiourea). Special forms of ARDS are showed in the table below 69 (Table VII). Table VII. Special forms of ARDS. Pharmaceutical Narcotic overdose Chemotherapy Salicylate intoxication Hydrochlorotiazide Contrast fluid Calcium antagonists overdose High altitude Neurogenic Pulmonary embolism Eclampsia Post cardioversion Post anesthesia Post cardiopulmonary bypass 143
  • 10. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . Management The main life threatening problem of ARDS is hypoxemia, that should be alleviated by recruiting and ventilating collapsed alveolar spaces and reducing the shunt. Hypoxemia cannot be corrected by the simple administration of oxygen. Mechanical ventilation via endotracheal intubation should be initiated as soon as possible. PEEP improves oxygenation reducing the intrapulmonary shunt. In general 5 to 20 cm H2O provides a reasonable balance among potential effects. In fact the heterogeneity of lung damage, due to the different disposition of areas of consolidation and atelectasis, causes that a certain amount of PEEP is appropriated in one region, too much in a normal region and too low in a more damaged region. The traditional ventilation included high flow with elevated tidal volume (12 ml/kg) and high plateau pressure (50 cm H2O), inducing ventilator-induced lung injury. A low tidal volume (6 ml/kg) and a low plateau pressure (max 30 cm H2O) decreased ARDS mortality from 40% to 31%70-73. Several studies that provide support for the presence of endogenous glucocorticoid inadeguacy in the control of inflammation and systemic inflammation-inducted peripheral glucocorticoid resistance in ARDS 74-78. Prolonged methylprednisolone administration (a loading dose of 2 mg/kg, followed by 2 mg/kg for 14 days, 1 mg/kg for the next 1 week, 0.5 mg/kg for the next 1 week, 0.25 mg/kg for the next 1 week and 0.125 mg/kg for the latest week, for a period of 32 days at all) may accelerate the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in ARDS79. b – Pneumonia Pneumonia is defined as an inflammation of the lung parenchyma, of the respiratory tract distal to terminal bronchioli. The most frequent etiology is infective (Common Acquired Pneumonia), although there are five different kinds of pneumonia: 1. Common acquired pneumonia; 2. Nosocomial pneumonia; 3. Aspiration pneumonia; 4. Atypical pneumonia; 5. Pneumonia in elderly. 144 Clinical Manifestation The clinical definition of common acquired pneumonia includes such typical signs and symptoms of lower respiratory tract infection, shared by both pneumonia and acute exacerbation of COPD. • Pleural pain, cough with purulent expectoration, dyspnoea, tachypnoea, and other local symptoms; high fever or chills, headache, arthritis, muscular pain. • New focal signs at the physical examination of the chest. The chest radiography shows pleural effusion, areas of consolidations and/or atelectasis. For the diagnosis of pneumonia, the presence of an infiltrate or a consolidation in chest radiography is necessary. We define nosocomial pneumonia if it occurs in patients admitted since at least 48 hours or discharged no more than 8 days before the onset of symptoms, or for outpatients or visitors that attended the hospital at least during the past 48 hours. The most frequent pathogens are aerobi bacteria Gram negative such as Enterobacter, Acinetobacter, Pseudomonas, Klebsiella, etc.; in the immunocompromised patients most frequently, Staphylococcus aureus and Legionelle. Table VIII shows the risk factors for nosocomial pneumonia. The aspiration pneumonia due to the entrance of fluids from stomach or upper respiratory tracts into the lower respiratory tracts, can be classified in consideration of the three different pulmonary damages: toxic, obstructive or infective 80 . Table IX, from IDSA guidelines, shows in synthesis clinical manifestations and therapeutic approach to the different forms. Atypical pneumonia is defined for the unusual manifestations with majority of systemic signs and symptoms (fever, Table VIII. Risk factors for nosocomial pneumonia. Elderly Severity of pathology Admittance in ICU – endotracheal intubation Mechanical ventilation Surgery Previous use of antibiotics
  • 11. Approach to respiratory failure in emergency department Table IX. Inoculum Pulmonary Clinical features Therapy Acid Chemical pneumonitis Acute dyspnea, tachypnea, tachycardia with Positive-pressure or with-out cyanosis bronchospasm, fever, breathing IV fluids, sputum: pink, frothy; radiograph: infiltrates tracheal suction in one or both lower lobes, hypoxemia Oropharyngeal bacterial Bacterial infection Usually insidious onset; cough, fever, purulent sputum; radiograph: infiltrate involving dependent pulmonary segment or lobe with or without cavitation Antibiotics Inert fluids Mechanical obstruction: reflex airway closure Acute dyspnea; cyanosis with or without apnea; pulmonary edema Particulate matter Mechanical obstruction Dependent on level of obstruction, ranging from acute apnea and rapid death to irritating chronic cough with or without recurrent infections Tracheal suction: intermittent positive pressure breathing with oxygen and isoproterenol Extraction of particulate matter, antibiotics for superimposed infection Modified from IDSA guidelines for CAP. arthralgias, headache, etc.) and a poor pulmonary and chest manifestations (cough without purulent sputum, no signs of consolidation at chest radiography). The more frequent agents involved are Chlamydia pneumoniae, Mycoplasma pneumoniae, Chlamydia psittaci, Coxiella burnetii. Several studies have shown that clinical, laboratory and radiographic features cannot reliably differentiate between different causative pathogens 81 . The diagnosis of Chlamydia pneumoniae is made serologically or by polymerase chain reaction techniques; both Chlamydia and Mycoplasma are relatively often detected in mixed infections with Streptococcus pneumoniae and Haemophilus influenzae, thus making difficult to define under what circumstances they could be considered the cause of pneumonia. Treatment is often empiric (Grade of recommendation A II): macrolide, doxicyclin, and ciprofloxacin (Grade of recommendation B III). The first step in a patient with a diagnosis of pneumonia is to assess the severity of illness and the need for hospital admission that were identified by the American Thoracic Society (ARS)82 and the British Thoracic Society (BTS) in 200183. The ATS rule is based on the presence of at least one major criterion (need for mechanical ventilation, an increase in the size of infiltrates by > 50% within 48 h, septic shock or the need of vasopressors for > 4 hours, and acute renal failure), or two minor criteria (respiratory rates > 30 breaths per minute, PaO2/FiO2 < 250, bilateral/multilobar pneumonia, arterial blood pressure 90/60 mmHg). The BTS rule is based on the presence of 2 main risk factors; if only one is present clinician should evaluate pre-existent comorbidities (age more that 50 years, congestive heart failure –Ib-, ictus –Ib-, coronary artery disease –III-, diabetes mellitus –Ia-, neoplasm –Ib). There are 4 prognostic negative factors: mental Confusion non pre-existent, Urea > 7 mmol/l, Respiratory rate > 30 breaths/min, systolic Blood pressure < 90 (or diastolic < 60 mmHg) (CURB). Management If oxygen blood parzial pressure is less than 70 mmHg, oxygen should be administered to obtain an increasing in saturation major that 90%. If obstructive pulmonary diseases don’t coexist, the inspiration fraction of O2 should be greater than 0.35. In seriously ill patients, if oxygen therapy is not necessary to mantain saturation between 85 and 90%, despite maximum medical treatment, NIV could be used to improve oxygenation, 145
  • 12. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . Table X. Guidelines Modifying factors/comments First choice Alternatives Outpatients ER LRTI# Aminopenicillin Canadian No modifying factor COPD, no recent antibiotics or oral steroids COPD, antibiotics or oral steroid within 3 months Macrolide New macrolide IDSA CDC ATS No modifying factor Cardiopulmonary disease or other modifying factor Respiratory FQ Doxycycline/macrolide/FQ+ Macrolide/doxycycline/ cefuroxime//co-amoxiclav New macrolide β-Lactman + macrolide or doxycycline Tetracyclines, cephalosporins respiratory quinolones, macrolides Doxycycline Doxycycline Co-amoxiclav 2nd GEN cephalosporin + macrolide Respiratory FQ Doxycycline Respiratory FQ Hospital treated general ward ERS Canadian β-Lactman + macrolide Respiratory FQ IDSA CDC ATS No modifying factor β-Lactman + macrolide β-Lactman + macrolide Azithromycin i.v. Cardiopulmonary dis or other modifying factor β-Lactman + doxycycline or macrolide Canadian P. aeruginosa not suspected P. aeruginosa suspected 2nd-3nd GEN cephalosporin + macrolide or FQ + rifampicin Respiratory FQ + β-lactman Ciprofloxacin + antipseudomonas β-lactman or AG IDSA P. aeruginosa not suspected 2nd-4th GEN cephalosporin + macrolide FQ FQ β-Lactman + doxycycline or FQ alone FQ ICU-treatment ERS Structural lung disease CDC ATS P. aeruginosa not suspected P. aeruginosa suspected Extended spectrum β-lactman + FQ or macrolide Antipseudomonas β-lactman + ciprofloxacin β-Lactman + macrolide or FQ β-Lactman + macrolide or FQ Antipseudomonas β-lactman + ciprofloxacin β-Lactman + macrolide Antipseudomonas β-lactman + AG + macrolide Respiratory FQ Antipseudomonas β-lactman + AG + respiratory FQ or macrolide ERS: European Respiratory Society; IDSA: Infection Diseases Society of America; CDC: Center for Disease Control and Prevention; ATS: American Thoracic Society; LRTI: lower respiratory tract infection; FQ: fluoroquinolone; GEN: generation; P. aeruginosa: Pseudomonas aeruginosa; AG: aminoglycoside. #: no distinction was made between community-acquired pneumonia and other LRTIs; +: depending on local resistance situation and underlying factors; §: risk factors for penicillin-resistant pneumococci or Gram-negative bacteria; /: risk factors for penicillin-resistant pneumococci or Gram-negative bacteria, including nursing home patients. 146
  • 13. Approach to respiratory failure in emergency department Table XI. Suggested strategy for empirical outpatients treatment of community acquired pneumonia in the immunocompetent adult. (Modified from Eur Respir J)84. CAP Clinical/epidemiological data indicating atypical pneumonia Macrolide or doxycycline No clinical/epidemiological data indicating atypical pneumonia Younger and previously well Older, COPD and or other severe chronic ilness Penicillin V or amoxicillin Amoxicillin ± clavulanic acid Therapy failure Therapy failure Macrolide or doxycycline Doxycycline or respiratory fluoroquinolone Table XII. Suggested strategy for empirical inhospital treatment of community acquired pneumonia in the immunocompetent adult. (Modified from Eur Respir J)84. Patient to moderate CAP Probable pathogen (cover required) Mild to moderate CAP All cases Streptococcus pneumoniae Chronic pulmonary disease Haemophilus influenzae and or post-influenza pneumonia Moraxella catharralis Postinfluenza pneumonia Staphylococcus aureus and drug addied Epidemiological chemical Legionella data indicating legionella Epidemiological clinical data indicating other atypicals Gram-negative cover nor routinely necessary (irrespective of patient’s age, or whether nursing home resident)97 Severe CAP All cases Mycoplasma pneumoniae and Chamydia pneumoniae Streptococcus pneumoniae Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, “atypical” agents and Gram-negative enteric bacilli Choice of empirical therapy Benzylpenicillin or amoxicillin clavulanic acid Cefotaxmeceftriaxone if high rate of hyghly penicillin-resistant pneumococci Co-amoxiclav, or 2nd/3rd generation cephalosporin (iv) 2nd/3rd generation cephalosporin (iv) Respiratory FQ, or macrolide + data benzylpenicillin/amoxixillin clavulanic or 2nd/3rd generation cephalosporin (iv) Macrolide or doxycycline Cefotaxime ceftriaxone macrolide rifampicin or benzylpenicilli respiratory FQ Pseudomanas aeruginosa need not be routinely FQ: fluoroquinolone. 147
  • 14. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . reduce respiratory rate and lessen dyspnoea. Moreover, NIV can be used as an alternative to tracheal intubation if patient became hypercapnic (Grade of recommendation C)10. Patients should have arterial systolic pressure > 90 mmHg and the diuresis (0.5-1 ml/kg/hour). The empirical antibiotic treatment recommended by international guidelines is summarized in Table X (from ERJ)84. It differs between outpatients and inhospital patients, and it’s based on severity of illness and the most likely pathogen involved in various patients categories (Table XI). Most of the outpatients should be treated with monotherapy, most often with beta-lactam alone (amoxicillin ± clavulanic acid or second and third generation intravenous cephalosporin). If therapy fails, Mycoplasma and/or Chlamydia pneumoniae may be involved and so treatment with doxycicline/ macrolide or fluoroquinolone should be initiated (Table XII). The inhospital patient should be treated within 8 hours from the admittance, with empirical therapy (amoxicillin ± clavulanic acid or second and third generation intravenous cephalosporin): it should not be delayed while waiting for the results of the examinations (hemocultures, culture of sputum, first of all). If patient has structural lung disease Pseudomonas should be suspected: piperacilline, piperacilline-tazobactam, cefepime, imipenem, meropenem should be administered. If aspiration pneumonia is suspected, a therapy against anaerobic bacteria should be initiated (beta lactamic antibiotics plus inhibitor of beta lactamase, clindamycin, metronidazol). If Pneumococcus is suspected, beta lactamic antibiotics plus inhibitor of beta lactamase (1 g each 6 hours), cefotaxime (1 g each 8 hours), ceftriaxone (1 g each 24 hours) should be administered, or, if patient is allergic, fluoroquinolones or quinopristin/ dalfopristin, or still linezolid or vancomycine. In general, it is important for efficacy, as well as to avoid development of resistance, that high enough or frequent enough dosing is used rather than extending therapy for > 7-10 days (except for treatment of the Legionnaires’ disease, where 2-3 weeks’ duration is recommended). 148 References 1) MEHTA S, HILL NS. Non invasive ventilation. Am J Respir Crit Care Med 2001; 163: 540-577. 2) BERSTEN AD, HOLT AW, VEDIG AE, SKOWRONSKI GA, B AGGOLEY CJ. Treatment of severe cardiogenic pulmonary oedema with continuous positive airway pressure delivered by face mask. N Engl J Med 1991; 325: 1825-1830. 3) MEHTA S, JAY GD, WOOLARD RH, HIPONA RA, CONNOLLY EM, CIMINI DM, DRINKWINE JH, HILL NS. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary oedema. Crit Care Med 1997; 25: 620-628. 4) MEECHAM JONES DJ, PAUL EA, GRAHAME-CLARKE C, WEDZICHA JA. Nasal ventilation in acute exacerbations of chronic obstructive pulmonary disease: effect of ventilator mode on arterial blood gas tensions. Thorax 1994; 49: 1222-1224. , 5) VITACCA M, RUBINI F FOGLIO K, SCALVINI S, NAVA S, AMBROSINO N. Non-invasive modalities of positive pressure ventilation improve the outcome of acute exacerbations in COLD patients. Intens Care Med 1993; 19: 450-455. 6) CONFALONIERI M, POTENA A, CARBONE G, PORTA RD, TOLLEY EA, UMBERTO MEDURI G. Acute respiratory failure in patients with severe community acquired pneumonia: a prospective randomized evaluation of noninvasive ventilation. Am J Respir Crit Care Med 1999; 160: 1585-1591. 7) ANTONELLI M, CONTI G, ROCCO M, BUFI M, DE BLASI RA, VIVINO G, GASPARETTO A, MEDURI GU. A comparison of noninvasive positive pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998; 339: 429-435. 8) ANTONELLI M, CONTI G, BUFI M, COSTA MG, LAPPA A, ROCCO M, GASPARETTO A, MEDURI GU. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: randomized trial. JAMA 2000; 283: 235-241. 9) AMERICAN THORACIC SOCIETY. International consensus conferences in intensive care medicine: non invasive positive pressure ventilation in acute respiratory failure. Am J Resp Crit Care Med 2001; 163: 283-291. 10) BAUDOUIN S, BLUMENTHAL S, COOPER B, et al. Non invasive ventilation in acute respiratory failure. BTS Standard of care committee. Thorax 2002; 57: 192-211. 11) GARETTO G. La Nuova Medicina d’Urgenza. Ed. C.G., Torino, 1994. 12) ALAT WORK GROUP. Update to the Latin American Thoracic Society. Recommendation on Infectious Exacerbation of COPD. Arch Bronconeumol 2004; 40: 315-325. 13) MIRAVITLLES M. Epidemiology of chronic obstructive pulmonary disease exacerbations. Clin Pulm Med 2001; 163: 1730-1754.
  • 15. Approach to respiratory failure in emergency department 14) MONSO E, RUIZ J, ROSELL A, MANTEROLA J, FIZ J, MORERA J, AUSINA V. Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med 1995; 152: 1316-1320. 15) CHRONIC OBSTRUCTIVE PULMONARY DISEASE. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax 2004; 59 (Suppl I): 1-132. 16) ANTHONISEN NR, MANFREDA J, WARREN CP HERSHFIELD , ES, HARDING GK, NELSON NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106: 196-204. 17) JONES PW. Health status measurement in chronic obstructive pulmonary disease. Thorax 2001; 56: 880-887. 18) ANTHONISEN NR, WRIGHT EC, HODGKIN JE. Prognosis in chronic obstructive pulmonary disease. Am Rev Respir Dis 1986; 133: 14-20. 19) BURROWS B. The course and prognosis of different types of chronic airflow limitation in general population sample from Arizona: comparison with the Chicago “COPD” series. Am Rev Respir Dis 1989; 140: S92-S94. 20) NICE GUIDELINES ON COPD. National clinical guideline on management of chronic obstructive pulmonary disease. Thorax 2004; 59 (Suppl 1): 1-132. 21) RUSSI EW, LEUENBERGER P BRANDLI O, FREY JG, GREBS, KI E, GUGGER M, PAKY A, PONS M, KARRER W, KUHN M, ROCHAT T, SCHIBLI R, SOLER M, WACKER J. Management of chronic obstructive pulmonary disease: the Swiss guidelines. Official Guidelines of the Swiss Respiratory Society. Swiss Med WKLY 2002; 132: 67-78. 22) THE COPDX PLAN. Australian and New Zealand Guidelines for the management of Chronic Obstructive Pulmonary Disease 2003. Med J Australia 2003; 178: S1-S37. 23) EUROPEAN RESPIRATORY SOCIETY GUIDELINES ON THE OF NEBULIZERS. Eur Respir J 2001; 18: 228-242. USE 24) LITTNER MR, ILOWITE JS, TASHKIN DP FRIEDMAN M, SER, BY CW, MENJOGE SS, WITEK TJ JR. Long-acting bronchodilation with oncedaily dosing of tiotropium (Spiriva) in stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 1136-1142. 25) VAN NOORD CORNELISSEN JA, BANTJE TA, ELAND ME, KORDUCKI L, PJ. A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group. Thorax 2000; 55: 289-294. 26) NHLBI/WHO WORKSHOP REPORT. Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. National Institutes of Health – National Heart, Lung and Blood Institute April 2001; 68. 27) VAN NOORD JA, DE MUNCK AKVELD ML, BOMMER AM. DR, BANTJE TA, HOP WC, Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium. Eur Respir J 2000; 15: 878-885. 28) IKEDA A, NISHIMURA K, KOYAMA H, IZUMI T. Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone. Chest 1995; 107: 401-405. 29) COMBIVENT INHALATION AEROSOL STUDY GROUP. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. Chest 1994; 105: 1411-1419. 30) THE COMBIVENT INHALATION SOLUTION STUDY GROUP. Routine nebulized ipratropium and albuterol together are better than either alone in COPD. Chest 1997; 112: 1514-1521. 31) GROSS N, TASHKIN D, MILLER R, et al. Inhalation by nebulization of albuterolipatropium combination (Dey Combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary disease. Dey Combination Solution Study Group. Respiration 1998; 65: 354-362. 32) CALLAHAN CM, DITTUS RS, KATZ BP Oral corticos. teroid therapy for patients with stable chronic obstructive pulmonary disease. A meta-analysis. Ann Intern Med 1991; 114: 216-223. 33) POSTMA DS, STEENHUIS EJ, VAN DER WEELE LT, SLUITER HJ. Severe chronic airflow obstruction: can corticosteroids slow down progression? Eur J Respir Dis 1985; 67: 56-64. 34) POSTMA DS, PETERS I, STEENHUIS EJ, SLUITER HJ. Moderately severe chronic airflow obstruction. Can corticosteroids slow down obstruction? Eur Respir J 1988; 1: 22-26. 35) DECRAMER M, DE BOCK V, DOM R. Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 153: 1958-1964. 36) GOSSELINK R, TROOSTERS T, DECRAMER M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am J Respir Crit Care Med 1996; 153: 976-980. 37) POSTMA DS, PETERS I, STEENHUIS EJ, SLUITER HJ. Moderately severe chronic airflow obstruction. Can corticosteroids slow down progression? Eur Respir J 1988; 1: 22-26. 38) POSTMA DS, STEENHUIS EJ, VAN DER WEELE LT, SLUITER HJ. Severe chronic airflow obstruction: can corticosteroids slow down progression? Eur J Respir Dis 1985; 67: 56-64. 39) DECRAMER M, DE BOCK V, DOM R. Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 153: 1958-1964. . 40) DECRAMER M, LACQUET LM, FAGARD R, ROGIERS P Corticosteroids contribute to muscle weakness in 149
  • 16. P Forte, M. Mazzone, G. Portale, C. Falcone, F Mancini, N. Gentiloni Silveri . . chronic airflow obstruction. Am J Respir Crit Care Med 1994; 150: 11-16. 41) DECRAMER M, STAS KJ. Corticosteroid-induced myopathy involving respiratory muscles in patients with chronic obstructive pulmonary disease or asthma. Am Rev Respir Dis 1992; 146: 800-802. 42) SENDEROVITZ T, VESTBO J, FRANDSEN J, MALTBAEK N, NORGAARD M, NIELSEN C, KAMPMANN JP. Steroid reversibility test followed by inhaled budesonide or placebo in outpatients with stable chronic obstructive pulmonary disease. The Danish Society of Respiratory Medicine. Respir Med 1999; 93: 715-718. 43) V ESTBO J, S ORENSEN T, L ANGE P, B RIX A, T ORRE P, VISKUM K. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 1999; 353: 1819-1823. 44) PAUWELS RA, LOFDAHL CG, LAITINEN LA, SCHOUTEN JP , POSTMA DS, PRIDE NB, OHLSSON SV. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med 1999; 340: 1948-1953. 45) Proceedings of the ATS Workshop on Refractory Asthma: current understanding, recommendations and unanswered questions. Am J Respir Crit Care Med 2000; 162: 2341-2351. 46) M C FADDEN ER Jr. Acute severe asthma. Am J Respir Crit Care Med 2003; 168: 740-759. 47) MCFADDEN ER JR, LYONS HA. Arterial blood gas tension in asthma. N Engl J Med 1968; 278: 10271032. 48) TAI E, READ J. Blood gas tension in bronchial asthma. Lancet 1967; 1: 644-646. 49) WENG TR, LANGER HM, FEATHERBY EA, LEVISON H. Arterial blood gas tension and acid-base balance in symptomatic and asymptomatic asthma in childhood. Am Rev Respir Dis 1970; 101: 274-282. 50) WADDEL JA, EMERSON PA, CUNSTONE RF Hypoxia in . bronchial asthma. Br Med J 1967; 2: 402-404. 51) APPEL D, RUBENSTEIN R, SCHRAGER K, WILLIAMS MH JR. LACTIC ACIDOSIS IN SEVERE ASTHMA. Lactic acidosis in severe asthma. Am J Med 1983; 75: 580-584. 52) MCFADDEN ER JR, ELSANADI N, DIXON L, TAKACS M, D EAL EC, B OYD KK, I DEMOTO BK, B ROSEMAN LA, PANUSKA J, HAMMONS T, ET AL. Protocol therapy for acute asthma: therapeutic benefits and cost savings. Am J Med 1995; 99: 651-661. 53) STRAUSS L, HEJAL R, GALAN G, DIXON L, MCFADDEN ER JR. Observations on the effects of aerosolized albuterol in acute asthma. Am J Respir Crit Care Med 1997; 155: 454-458. 54) M C FADDEN ER J R , S TRAUSS L, H EJAL R, G ALAN G, DIXON L. Comparison of two dosage regimens of albuterol in acute asthma. Am J Med 1998; 105: 12-17. 150 55) MCFADDEN ER JR, ELSANADI N, STRAUSS L, GALAN G, DIXON L, MCFADDEN CB, SHOEMAKER L, GILBERT L, WARREN E, HAMMONDS T. The influence of parasympatholytics on the resolution of acute attacks of asthma. Am J Med 1997; 102: 7-13. 56) KOROSEC M, NOVAK RD, MYERS E, SKOWRONSKI M, MCFADDEN ER Jr. Salmeterol does not compromise the bronchodilator response to albuterol during acute episodes of asthma. Am J Med 1999; 107: 209-213. 57) RATTO D, ALFARO C, SIPSEY J, GLOVSKY MM, SHARMA OP Are intravenous corticosteroids required in . status asthmaticus? JAMA 1988; 260: 527-529. 58) WENZEL S. Severe Asthma in adults. Am J Respir Crit Care Med 2005; 172: 149-160. 59) MEHTA S, JAY GD, WOOLARD RH, HIPONA RA, CONNOLLY EM, CIMINI DM, DRINKWINE JH, HILL NS. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit Care Med 1997; 25: 620-628. 60) BERSTEN AD, HOLT AW, VEDIG AE, SKOWRONSKI GA, B AGGOLEY CJ. Treatment of severe cardiogenic pulmonary edema with continuous positive airway pressure delivered by face mask. N Engl J Med 1991; 325: 1825-1830. 61) LIN M, YANG YF CHIANG HT, CHANG MS, CHIANG BN, , CHEITLIN MD. Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema. Short-term result and long-term follow up. Chest 1995; 107: 1379-1386. 62) RASANEN J, HEIKKILA J, DOWNS J, NIKKI P VAISANEN I, , VIITANEN A. Continuous positive airway pressure in acute cardiogenic pulmonary edema. Am J Cardiol 1985; 55: 296-300. 63) PIANTADOSI CA, SCHWARTZ DA. The acute respiratory distress syndrome. Ann Intern Med 2004; 141: 460-470. 64) HOGG JC, DOERSCHUK CM. Leucocyte traffic in the lung. Annu Rev Physiol 1995; 57: 97-114. 65) DOYLE RL, SZAFLARSKI N, MODIN GW, WIENER-KRONISH JP, M ATTHAY MA. Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med 1995; 152: 1818-1824. 66) Z ILBERBERG MD, E PSTEIN SK. Acute lung injury in medical ICU: comorbid conditions, age, aetiology, and hospital outcome. Am J Respir Crit Care Med 1998; 157: 1159-1165. 67) MONCHI M, BELLENFANT F CARIOU A, JOLY LM, THEBERT , , D, LAURENT I, DHAINAUT JF BRUNET F. Early predictive factors of survival in the acute respiratory distress syndrome. A multivariate analysis. Am J Respir Crit Care Med 1998; 158: 1076-1081. 68) L UHR OR, A NTONSEN K, K ARLSSON M, A ARDAL S, THORSTEINSSON A, FROSTELL CG, BONDE J. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group. Am J Respir Crit Care Med 1999; 159: 18491861.
  • 17. Approach to respiratory failure in emergency department 69) KAKOUROS NS, KAKOUROS SN. Non cardiogenic pulmonary edema. Hellenic J Cardiol 2003; 44: 385391. 78) MEDURI GU, CHROUSOS GP Duration of glucocorticoid . treatment and outcome in sepsis: is the right drug used the wrong way? Chest 1998; 114: 355-360. 70) VENTILATION 79) MEDURI GU, TOLLEY EA, CHROUSOS GP STENTZ F Pro, . longed methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. Am J Respir Crit Care Med 2002; 165: 983-991. WITH LOWER TIDAL VOLUMES AS COMPARED WITH TRADITIONAL TIDAL VOLUMES FOR ACUTE LUNG INJURY AND THE ACUTE RESPIRATORY DISTRESS SYNDROME. The acute respiratory distress syndrome network. N Engl J Med 2000; 342: 1301-1308. 71) EICHACKER PQ, GERSTENBERGER EP BANKS SM, CUI X, , NATANSON C. Metanalysis of acute lung injury and the acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 2002; 166: 1510-1514. 72) B ROWER RG, M ATTHAY M, S CHOENFELD D. Metaanalysis of acute lung injury and acute respiratory distress syndrome trials. (letter). Am J Respir Crit Care Med 2002; 166: 1515-1517. 73) STEINBROOK R. Trial design and patient safety-the debate continues. N Engl J Med 2003; 349: 629630. 80) BARTLETT JG, DOWELL SF, MANDELL LA, FILE JR TM, MUSHER DM, FINE MJ. Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America. Clin Infect Dis 2000; 31: 347-382. 81) WOODHEAD M. Treatment of community-acquired pneumonia. In: Marrie TJ, ed. Community acquired pneumonia. New York, NY, Kluwer Academic/Plenum Publishers, 2001; pp. 163-178. 74) M ELBY JC, S PINK WW. Comparative studies on adrenalcortical function and cortisol metabolism in healthy adults and in patients with shock due to infection. J Clin Invest 1958; 37: 1791-1798. 82) LIM WS, MACFARLANE JT, BOSWELL TC, HARRISON TG, ROSE D, LEINONEN M, SAIKKU P Study of community . acquired pneumonia aetiology (SCAPA) in adults admitted to hospital: implications for management guidelines. Thorax 2001; 56: 296-301. 75) REINCKE M, ALLOLIO B, WURTH G, WINKELMANN W. The hypothalamic-pituitary-adrenal axis in critical illness: response to dexamethasone and corticotropin-releasing hormone. J Clin Endocrinol Metab 1993; 77: 151-156. 83) AMERICAN THORACIC SOCIETY. Guidelines for the management of adults with community acquired pneumonia. Am J Respir Crit Care Med 2001; 163: 1730-1754. 76) BRIEGEL J, FORST H, HELLINGER H, HALLER M. Contribution of cortisol deficiency to septic shock. Lancet 1991; 338: 507-508. 77) ANNANE D, SEBILLE V, TROCHE G, RAPHAEL JC, GAJDOS P BELLISSANT E. A 3-level prognostic classification , in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000; 283: 1038-1045. 84) ORTQVIST A. Treatment of community acquired lower respiratory tract infections in adults. Eur Respir J 2002; 20 (Suppl. 36): 40s-53s. 85) NHLBI/WHO WORKSHOP REPORT. Global Initiative for Chronic Obstructive Lung Disease (COLD): Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Institutes of Health–National Heart, Lung and Blood Institute, April 2001. 151