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Home , Kerley lines, Respiratory failure

European Review for Medical and Pharmacological Sciences 2006; 10: 135-151 Approach to 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 second mechanism (mismatch in blood The goal of this review is to provide update rec- gas exchanges) is due to the following differ- ommendations that can be used by emergency ent pathologies: physicians who provide primary cares to pa- tients with Respiratory Failure (ARF), from • Adult acute respiratory distress syn- the admission to an emergency department drome; through the first 24 to 48 hours of hospitaliza- • Neonatal respiratory distress syndrome; tion. This work wants to address the diagnosis • Acute cardiogenic pulmonary oedema; and emergency medical care of ARF and the • Severe status asthmaticus; management of medical complications. • ; State of the Art: A lot of statement has been developed for the early management and treat- • Airspace collapse (); ment of ARF; moreover, over the last fifteen • . years, we have assisted to the rise of a new technique of ventilation, in the Emergency De- The clinical of patients partment: Non Invasive Ventilation. This kind of with ARF, refer to the two main manifesta- ventilation was firsthy applied in Intensive Care tions of pulmonary diseases: arterial hyper- and in Respiratory Care Unit. Randomized con- capnia and . trolled clinical trials have showed its usefulness in the early treatment of several forms of ARF, The pathophysiology of is together with medical therapy. based on four main mechanisms: Increase in CO2 production (for istance, Key Words: parenteral feeding with high doses of carbo- Respiratory failure, , , hydrates; high body temperature, etc.) Pneumoniae, Therapy in emergency department. Deterioration in gas exchanges as the in- crease in alveolar death space ventilation (for istance in Chronic Obstructive Pulmonary Disease – COPD –, because of mismatch in ventilation/perfusion ratio, and in pulmonary embolism); Introduction Deterioration in respiratory mechanics that involves a huge effort, an increase in res- Acute Respiratory Failure (ARF) was de- piratory work and the development of a rapid ↑ fined as the inability of the shallow CO2; to exchange gases and to oxygenate the blood Alteration in the mechanism of control of adequately1-8. We can distinguish two mecha- the ventilation (for istance, in chronic hyper- nisms at the basis of ARF: capnia, we observe a decrease in ventilatory 1. Failure in pulmonary ventilation (pump drive with an increase in tolerance threshold failure); to CO2; it happens in metabolic alkalosis 2. Failure in gas exchanges (lung failure). too). The hypoxemia is due to different patho- The first one is due to neuromuscular dis- physiological mechanisms: eases, chest wall deformities, obstructive pul- • ; monary diseases (Table I). • Alteration in gas diffusion;

Corresponding author: [email protected]; [email protected] 135 P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Table I. Moreover he has to take an arterial blood gas sample and a peripheral venous blood Neuromuscular Drugs abuse sample to evaluate CK, CKMB, T-tropo- diseases Cervical tetraplegia Curare/strychnine/ nine, LDH, AST, ALT and hemochrome. phosphate poisoning 2. At the same time he must evaluate the Guillaine-Barré syndrome neurological state, in order to call for the Miastenia gravis; hereditary/ resuscitator if Kelly score (Table II) is acquired myopathies more than 3. /Poliomyelitis 3. If neurological state is not compromised Chest wall deformities Bilateral or hypertensive patient can be managed by emergency physician, entirely. Arterial blood gas Post-traumatism (ABG) evaluation: Obstructive diseases Severe Status Asthmaticus – Hypoxemia with hypercapnia → pump Central airways obstruction failure due to or chest wall deformities; Lung failure due to COPD or acute asthmatic status. • Mismatch in ventilation/perfusion ratio; This last situation can be treated with • Pulmonary shunt. pharmacological therapy and/or with non invasive ventilation, if indicated. Pa- Which are the clinical signs and symptoms tient must undergo endotracheal intuba- of hypoxemia and hypercapnia? The first one tion (ETI) if his clinical conditions dete- shows with , tachycardia, riorate. mental confusion, changes of personality, – Hypoxemia with no hypercapnia → restlessness, , hyper/hypotension, ar- lung failure due to ARDS or cardio- rhythmias and palpitations. Hypercapnia, in- genic pulmonary oedema or pulmonary stead, shows with sleepiness, mental confu- embolism or pulmonary infection. If sion, cephalea, convulsions, arrhythmias, oxygen saturation in more than 90% miosis, , peripheral vasodilation, continue to administer O2 with face hypotension and coma. mask and high flows. If oxygen satura- The first goal of the initial diagnostic eval- tion is less than 90% consider the use uation is to understand the underling causes, of Non Invasive Ventilation (NIV), to- and so to do differential diagnosis among all gether with medical therapy. pathologic conditions that showed the most 4. Clinical evaluation must be associated important clinical symptom of this illness: with radiological evaluation (Chest X- dyspnoea. Rays) and with continuous ABG evalua- tions (after 1 hour and after each chang- ing in clinical conditions). Patient must undergo endotracheal intubation if his A – Approach to Patients clinical conditions deteriorate. with Dyspnoea Evidence and Information Sources Clinical Evaluation A comprehensive literature search was A patient with ARF usually presents with performed in order to select the latest rec- signs of respiratory distress: dyspnoea, cyanosis, , accessory muscle use, paradoxical breathing and tachycardia. Pri- Table II. Kelly scale. mary care physician must apply the algorithm •Awoke patient, he executes 3 complex orders A-B-C-D, in order to exclude an Acute Up- •Awoke patient, he only executes simple orders per (AUAO), first of all, • Sleepy patient, he can be awaken under verbal and then he must operate as following: orders 1. He has to administer high flows of oxy- • Sleepy patient, he can be awaken under physical gen, to measure blood pressure, to take stimulus • Coma with no brainsteam alteration rate, respiratory rate, oxygen satu- • Coma with brainsteam alteration ration, to make an electrocardiogram.

136 Approach to respiratory failure in emergency department

Table III.

Infectious Viral laryngotracheitis () Bacterial epiglottiditis Bacterial Neoplasm Subglottic hemangioma Tracheal and endobronchial neoplasms Thyroid and mediastinal tumors Traumatic External bodies aspiration Anaphylaxis Obstructive Sleep Syndrome (OSAS) Neurogenic diseases Bilateral paralysis of recurrent nerve

Modified by G. Garetto, La Nuova Medicina d’Urgenza, Ed. C.G. Torino11.

ommendations for the early diagnosis and ryngeal obstruction). We usually observe the therapy of the pathologies below. asymmetries in diaphragmatic ranges, in res- In developing of the present guidelines we piratory movements, in the intercostal and considered the latest evidences in the man- supraclavicular re-entrances. agement of dyspnoea, asthma, COPD, ARDS If the physician suspects an epiglottiditis, he and we applied the ATS Consensus Confer- should be cautious in carrying out clinical ex- ence indications9 and the BTS guidelines10 for amination: in fact he could provoke a com- the use of NIV in ARF. plete obstruction stimulating with the tongue depressor. Moreover, if respiratory distress continues and the patient is stable (rapid shal- low breathing, valid , conscious, lucid B – Approach to Patients with and alert patient but with no cardiovascular al- Acute Upper Airway Obstruction terations) physician should take blood pres- (AUAO) sure and oxygen saturation, continuously, and often control ABG. If patient presents with he should follow the Ad- Etiology vanced Algorithm. In a second The causes of AUAO can be summarized time physician should make differential diag- in Table III11. nosis between epiglottiditis and viral croup. Anaphylaxis: if patients present with glot- Clinical Evaluation tis’ oedema should be immediately intubated We distinguish two different types of upper before developing complete obstruction of airway obstruction: the extra thoracic pre- upper airways. Then they should be submit- sents inspiratory , because of the col- ted to infusion therapy with adrenaline (1 mg lapse of upper extra thoracic airways, during in bolus repeatable), corticosteroids (hydro- the inspiration when tracheal pressure is mi- cortisol – methylprednisolone) at high doses, nor than atmospheric one. The intra thoracic fluids. one that presents expiratory stridor, because the extrathoracic airways collapse during the expiration, when the intrapleural pressure is Table IV. Infectious AUAO. greater than atmospheric one. The stridor is the main symptom of Supraglottic Severe (> 10 years) AUAO (Table IV), and it’s often associated (> 10 years) with cyanosis, loss of consciousness, nape’s (> 3 years) Epiglottiditis (3-7 years) hyperextension (especially in the epiglottidi- Subglottic Viral croup (3 months-3 years) tis), trismus (especially in the peritonsillar ab- Bacterial tracheitis scess), dysphagia (severe epiglottiditis or pha-

137 P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Foreign bodies obstruction: do not intro- The clinical approach to these patients duce fingers into the oral cavity in order to could be differentiated on the base of their take it out: it could slip down. If patient can conditions at the admission to the first aid. speak the physician could remove it with a Preserved and stable vital functions: if up- powerful blow in the interscapular zone per airways are pervious, if there are no car- (from one to four powerful blows). Moreover dio-vascular troubles and Kelly score is “1” he can try with Heimlich’s manoeuvring. This and patient presents only dyspnoea, deliver one can be performed with supine patient, in oxygen with facial mask and control arterial case of loss of consciousness. If saturation and blood pressure continuously. cannot be still removed, patient should be If arterial blood sample shows an oxygen sat- submitted to endoscopic removal, or to uration more than 90% and a PaCO2 less cricothyroidotomy, or to tracheostomy. than 45 mmHg, evaluate ABG after 1 hour and control clinical conditions. Chest radiog- raphy should be done as soon as possible, to help the physician in differential diagnosis C – Approach to Patients with ARF among neuromuscular diseases, chest wall de- Due to Neuromuscular Diseases or formities and brainstem pathologies. Chest Wall Deformities Preserved But Instable Vital Functions Cardio-circulatory arrest: ask for emer- Classification gency team and follow the algorithm ALS for See Table V for the classification the . Patient will be admitted to the (ICU). Signs and Symptoms of Hypoventilation • Rapid • Paradoxical breathing •Alternating breathing D – Approach to Patients with • Inability in carrying out a valid cough ARF Due to COPD • Shortness of breathing (at the end). The term COPD encompasses two well de- In patients with chest wall diseases, ARF is fined entities: emphysema and chronic bron- due to hypoventilation with an increase in chitis. Emphysema is characterized by perma- respiratory work and rapid shallow breathing. nent and abnormal enlargement of airspace, Hypercapnia and hypoxemia associated with distal to the bronchiole, associated to a de- hypoventilation due to neuromuscular dis- struction of alveolar wall, without evident fi- eases are due to different mechanisms: brosis, and to an obstruction of distal lower • Muscular weakness; airway. is defined only by a clinical • Decrease of pulmonary and thoracic definition as presence of cough and expecto- compliance; ration for more than three months per year • Increase in respiratory work; for more than two consecutive years. The key • Decrease in central sensibility. 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 ob- Table V. Infectious AUAO. struction to forced expiratory airflow. COPD is a slowly progressive disease char- Chest wall deformities Kyphoscoliosis Obesity-Hypoventilation acterized by punctuated exacerbations two or syndrome three times a year in patients with significant -Thoracoplastic obstruction. It is identified by the presence of airflow limitation that is not fully reversible Bilateral diaphragmatic and does not change markedly over several paralysis Wandering costal flap months. The disease is predominantly caused Neuromuscular diseases by smoking. The exacerbation, in most cases its due to infections, especially bacterial in-

138 Approach to respiratory failure in emergency department fections (level II of evidence)12. The guiding management of patients with acute pathogens most often involved in COPD ex- exacerbation of COPD (level of hierarchy acerbations are Haemophilus influenzae, IV). Spirometry, however, is fundamental to Streptococcus pneumoniae, Moraxella ca- making diagnosis of COPD because is the on- tarrhalis13,14; less often, gram negative bacte- ly accurate method of measuring the airflow ria, Chlamydia pneumoniae and Mycoplasma obstruction in patients. It cannot contributes pneumoniae. Among viruses have been iden- to the severity of COPD (level of hierarchy tified: Rhinovirus, virus, Parain- IV) or distinguish asthma from COPD; it is a fluenza virus, Coronavirus, Respiratory Syn- poor predictor of disability and quality of life cytial Virus, Adenovirus. The cause of exac- in COPD (level of hierarchy IV)17; it predicts erbation may be unidentifiable up to 30% of prognosis of patients (level of hierarchy exacerbation15. IV)18,19.

Clinical Evaluation Serological Assays Are Only of The diagnosis of the exacerbations is clini- Epidemiological Value cal and is based on three parameters: increas- samples for microbiological tests ing in sputum production, purulent expecto- (using Gram stain and culture) is indicated in ration, worsening dyspnoea. There is a severi- seriously ill patients, if sputum is persistently ty scale for exacerbations based on these present and purulent, or if there is a history findings16: type 1 (severe exacerbations) have of prior treatment failure (level of hierarchy all of the above symptoms; type 2 (moderate IV). exacerbations) present only two of the three Arterial blood gas sample is necessary to symptoms; type 3 (mild exacerbations) pre- assess the severity of exacerbation and for sent only one of the symptoms but associated the initial management of the patient. More- with one of the following at least: an upper over, patients who have low PaO2, high infection in the past five PaCO2, low pH are more likely to relapse days, fever, increasing in cough or wheezing, within 14 days of initial presentation. increasing in respiratory rate or in the heart ECG and/or Echocardiogram is useful to rate by 20% above the baseline. assess cardiac status if there are features of Each patient ranks the importance of dif- cor pulmonale (level of hierarchy IV). ferent symptoms individually, however CT scan of the thorax is necessary in sus- breathlessness is the most significance symp- pect of pulmonary embolism. It is useful (lev- tom. Individual symptoms are not useful in el of hierarchy IV) to investigate symptoms making or excluding the diagnosis of COPD that seem disproportionate to the spirometric (level IV of hierarchy)15. impairment, to investigate some suspect ab- normalities in . Additional Diagnostic Tests Reversibility testing: there is a consider- Chest radiography: some observational able variability in change in FEV1 in response studies showed substantial rate of chest radi- to the same stimulus from day to day, so it is ograph abnormalities. However, chest radiog- virtually impossible to interpret the response raphy is not routinely necessary during exac- to an individual reversibility test unless the erbations, neither for the diagnosis (level of response is very large (an increase in FEV1 hierarchy IV). It could be useful if there is more than 400 ml). Reversibility testing is not the suspect of pneumonia, or pneumothorax recommended in the latest guideline pro- or aspiration (such as in neuromuscolar dis- duced jointly by the American Thoracic Soci- eases), or if patient is non-responsive to the ety and the European Respiratory Society. therapy. As chest radiography can sometime Referral for specialist advice: these are reveal a parenchymatous pulmonary lesion made when clinically indicated, at all stages such as tuberculosis or bronchial carcinoma, of disease, not only in the most severely dis- patients who have not had a radiography pri- abled patients (level of hierarchy IV). or to the exacerbation should obtain one12. Spirometry: spirometric assessment, at the Need of Hospital Management time of presentation, or during the course of Most patients with acute exacerbation of treatment, is not useful in judging severity or COPD can be managed at home, but some of

139 P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri them need hospital treatment. This may be puff (40-80 microg) four times daily. For because of the following reasons: more severe exacerbations, 0.5 mg each 8 • Need for therapies that are not available hours (0.5 mg corresponds to 40 gtts of 0.25% at home (such as non invasive ventila- solution). The duration of action of short act- tion); ing inhaled anticholinergic agents is greater • Severe breathlessness; than that of beta 2 agonists (grade A)22. More • Poor/deteriorating general conditions; recently, several studies have reported • Cyanosis; favourable effects with tiotropium a new long •Worsening peripheral oedemas; acting anticholinergic that • Impaired neurological conditions, men- must be inhaled once daily23,24. tal confusion; The duration of action of short acting anti- • Acute onset; cholinergic agents is greater than that of • Significant comorbility particularly for short acting beta-agonists25 (grade of recom- heart diseases; mendation A). The combination of beta ago- • Changes in chest radiograph; nists and anticholinergics is more effective •Significant alteration in arterial blood and better tolerated than higher doses of ei- gas analysis (PaO2 < 60 mmHg; pH < ther agents used alone (grade of recommen- 7.35). dation A)26-27. The bronchodilator effects of short acting beta agonists (i.e. salbutamol) Management disappear within 4-6 hours; so for severe ex- The following assessment about the man- acerbations is acceptable to increase the agement in acute setting of COPD are based number of administrations. Table VI (modi- on the analysis of the most recent guidelines fied from “COPDX plan: Australian and from 2001 to 200420-23. New Zeland guidelines for managements of acute exacerbation of COPD”) shows the use of bronchodilators according to the severity Bronchodilators are central in manage- of COPD. ment of symptoms of acute exacerbation of The duration of action of short acting in- COPD. However they do not modify the de- haled anticholinergic agents is greater than cline of lung function or, by inference, the that of short acting beta-agonists (salbutamol, prognosis of the disease (grade B). Anti- terbutaline) (grade of recommendation A). cholinergic drugs inhibit vagal stimulation of The use of both of them is more effective and the bronchial tree and are associated with a better tolerated than the use of each one reduction of the smooth muscle tone and an alone (grade of recommendation A)26-31. impairment of bronchial gland secretion. The Long-acting beta2-agonists (salmeterol and bronchodilating effects of short acting in- formoterol) provide bronchodialtion for 12 haled anticholinergics last up to 8 hours after hours and are the first line treatment of acute the administration (grade A). If administered severe asthma. Moreover they provide sus- with metered-dose inhaler (MDI), the recom- tained relief in moderate to severe exacerba- mended dose of ipratropium bromide is 2-4 tion of COPD (grade of recommendation A).

Table VI.

Severity FEV1 Suggested treatment

Mild COPD 60%-80% Intermittent bronchodilators – salbutamol (200 µg) or ipratropium bromide (40 µg) Moderate COPD 40%-59% Intermittent or regular bronchodilators – salbutamol (200-400 µg four times daily) or ipratropium bromide (40 µg four times daily) Combination bronchodilators may be considered Severe COPD < 40% Regular combination bronchodilators – salbutamol (200-400 µg four times daily) and ipratropium bromide (40-80 µg four times daily)

Modified from GOLD85 [evidence level D]. FEV = forced expiratory volume in one second. COPD = chronic ob- structive pulmonary disease.

140 Approach to respiratory failure in emergency department

At the following dosage, salmeterol (50 mi- if it fails. A decision about tracheal intuba- crog twice daily) and formoterol (12 microg tion should be taken before initiating NIV in twice daily) improve the health related quali- each patient. ty of life, lung function and symptoms. THERAPY THEOPHYLLINE should be used in patients with Theophylline is a non selective inhibitor of purulent sputum and should be administered phosphodiesterase. Besides bronchodilation according to the stage of the disease (mild, it increases central respiratory drive, respira- moderate or severe) and appropriate to the tory muscle endurance, mucociliary clear- bacterial agents probably involved. So in the ance, cardiac output and dilation of pul- mild stage with a suspected infection by Strep- monary arteries. Theophyllines are rarely tococcus pneumoniae, Haemophilus influen- used because of their narrow therapeutic in- zae, Chlamydia pneumoniae, Mycoplasma dex and the potential side effects (grade of pneumoniae, Moraxella catarrhalis the recom- recommendation A). mended treatment is amoxicillin-clavulanic acid (or other more inhibiting beta-lactams available such as ampicillin-sulbactam and Chronic treatment with oral glucocorti- amoxicillin-sulbactam), at dosage of 875/125 coids should not be used in COPD (grade of mg/12 h for ten days or cefuroxime (500 mg/12 recommendation A)32-41. In fact their pro- h for 10 days) with azithromycin (500 mg/day longed use do not modify the long term de- for three-five days) or clarithromicin (500 mg cline of FEV1. Systemic preferable oral gluco- twice daily for 1 week). If patients have one or corticoids are beneficial in the management more risk factors add moxifloxacin/gati- of acute exacerbation of COPD (grade of floxacin/levofloxacin (respectively 400 mg/day, recommendation A). Probably they improve 400 mg/day and 500 mg/day for 7 days) and the rate of lung function during the first 72 telithromycin (800 mg/day for 5 days). If pa- hours. Many recent COPD guidelines recom- tients have a moderate or severe condition in- mend the use of a short course (two weeks) travenous treatment may sometimes be neces- of oral glucocorticoids in a dosage of 0.5 mg sary. The first line therapy, if enteric bacteria of prednisone or prednisolone/kg body or penicillin resistant streptococcus is involved weight. Inhaled glucocorticoids should be are quinolones, piperacillin-tazobactam and, if considered in patients with a documented re- there is a suspected infection by Pseudomonas sponse or those who have severe COPD with aeruginosa, ceftazidime, imipenem or frequent exacerbations (grade of recommen- meropenem or cefepime. dation B). Patients with clinically significant acute bronchodilator reversibility may bene- fit from long term inhaled therapy42-44. Management of Acute Asthma

OXYGEN THERAPY AND VENTILATORY SUPPORT10 A recognized definition of acute asthma It’s indicated in patients with hypoxia to in- must be still developed, despite numerous crease the oxygen blood saturation up to clinical definition have been proposed in dif- 90%. NIV has been shown to be an effective ferent workshops, working group, consensus treatment for acute hypercapnic respiratory conferences and national and international failure, particularly in patients with acute ex- guidelines. The following table shows the ma- acerbation of COPD in whom a respiratory jor and minor criteria established by the persist despite maximum medical American Thoracic Society in 2000, to define treatment on controlled severe asthma45. (grade of recommendation A). All the stud- According to consensus guideline, a severe ies about the use of NIV in acute exacerba- episode is characterized by almost one of the tion of COPD have excluded patients following events: deemed to warrant immediate intubation. 1. Accessory muscle activity; NIV in fact should be undertaken as a thera- 2. Paradoxical pulse exceeding 25 mmHg; peutic trial with a view to 3. Heart rate > 110 beats per minute;

141 P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

4. Respiratory rate > 30 breaths per minute; Nebulized corticosteroids have been used 5. Arterial saturation less than 90%. as a substitute of oral corticosteroids in mod- erate exacerbations of adult asthma; they This clinical features are associated with a have been shown to have an oral steroid spar- forced expiratory volume or a peak expirato- ing effect (Grade of recommendation A)23. ry flow rate less than 50%. In fact the sine Patients that are resistant or slowly respon- qua non of an episode of acute asthma is the sive to beta-agonists need corticosteroids reversible, non uniform increase in airway more urgently52-56. Methylprednisolone obstruction that induces diminished flow rate, should be administered at dosage of 1 mg/kg hyperinflation of the lung and premature air- of body weight during the acute attack. The way closure. Moreover with the increase in US guidelines recommend 120-180 mg daily work of breathing and in expiratory effort the of methylprednisolone given intravenously dynamic hyperinflation rises and auto-posi- (in three or four doses). It must be repeated tive end expiratory pressure (PEEP) devel- for 48 hours in those admitted, followed by ops. 60-80 mg/day until the FEV1 reach the 70% Arterial blood gas examination: it typically of normal. Oral prednisone (60 mg/day) can shows hypoxemia, , respiratory al- be substituted57. kalosis46-50. The more severe is the attack, the Methylxanthines, althought may have anti- lower is the arterial oxygen saturation. How- nflammatory properties, are considerably less ever most asthmatic patients don’t develop effective than the sympathomimetics and marked hypoxemia and, also in severe at- produce more significant side effects23-46. tacks, it’s very infrequent that oxygen tension Compared to COPD, insufficient evidence decrease under 50 mmHg. Respiratory acido- exists to recommend the use of NIV for asth- sis follows hypercapnia. With extreme flow ma patients; there is also insufficient evi- limitation metabolic acidosis develops. In dence to recommend Continuous Positive fact, if cardiac output is compromised devel- Airway Pressure (CPAP) in acute asthma ops lactic acidosis because of the hypoperfu- (Grade of recommendation C). The role of sion of peripheral tissue; in addition the in- NIV is not yet clear established57 and it could creased oxygen consumption by respiratory delay the use of endotracheal intubation muscles also contributes. It may also be in- when it is necessary. duced by aggressive administration of non se- lective sympathomimetics51.

Managements E – Approach to Patients with In hospital settings for asthmatic patients Hypoxemic ARF the driving gas should be oxygen for acute ill patients. Moderately short-acting beta2- a – Pulmonary Oedema adrenergic agonists such as salbutamol and The definition of “pulmonary oedema” is terbutaline have rapid onset of action and the overflow of fluid from the lung’s capillary provide more bronchodilation than do to the alveolar spaces. We can distinguish two methylxanthines and anticholinergics, making different entities of this pathology: cardio- them the first line treatment for acute illness. genic pulmonary oedema and non-cardio- Adult patients with acute asthma should be genic pulmonary oedema also called ARDS given 2.5-5 mg of salbutamol or 5-10 mg of (Acute Respiratory Distress Syndrome), that terbutaline (Grade of recommendation B23. can be distinguished by clinical signs and in- There is evidence that additional benefit can strumental examinations, although they pre- be obtained by adding anticholinergic treat- sent the same clinical symptoms. ment such as ipratropium bromide 500 mi- The acute cardiogenic pulmonary oedema crog (Grade of recommendation A). Treat- is a hydrostatic oedema due to an impaired ment should be repeated if patient is non re- function of left ventricle caused by coronary sponsive to the therapy. In near fatal asthma, artery disease, myocarditis, cardiomyopathy, the use of intravenous salbutamol (5 mi- hypertension, congenital heart diseases. It oc- crog/min) and adrenaline (1 mg repeatable curs when the pulmonary capillary pressure for three times each 15 minutes), is effective. rises to value exceeding plasma colloid-os-

142 Approach to respiratory failure in emergency department motic pressure (approximately 25 mmHg). pressure. The American - European Consen- Clinical examination reveals a low flow state sus Conference on ARDS defined the severi- with wet , jugular venous distention, ty of the pathology by the ratio of third tone (S3 gallop), cardiomegaly. Con- PaO2/FiO2: a ratio of 300 or less defines the cerning laboratory tests, ECG could shows acute lung injury (ALI); a ratio of 200 or less signs of ischemia or infarction. There could defines ARDS regardless of the amount of be an increasing in cardiac enzymes and, at PEEP needed to support oxygenation63. The the radiography, perihilar distribution of pathogenesis is due to the lung damage, that oedema and the appearance of Kerley lines. causes an increasing in permeability of capil- Pulmonary capillary wedge pressure exceeds lary endothelium and an alteration of lung 18 mmHg. alveolar-capillary barrier with overflow of The treatment of acute pulmonary oedema fluid into the alveolar and interstitial space, is based on the use of oxygen, nitrates, diuret- without increasing in pulmonary circulatory ics and, if coexists cardiogenic , in- pressure. The damage involves both the en- otropes. dothelial and epithelial surface; the activated Furosemide and nitrates (10 microg/min) endothelium participates and partly drives are the first line of medical treatment and the neutrophil inflammatory response that should be administered, together with mor- contributes to edema formation and fibro- phine, if arterial systolic blood pressure ex- sis64. The most common cause of ARDS is a ceed 100 mmHg. They promote diuresis severe infection and it accounts for approxi- and vasodilation and so act both on the mately half of cases. It could present as a lo- pre-load and on the post-load of the heart, calized or systemic disease and the most reducing cardiac work and improving the common agents involved are gram-negative ejection fraction. If arterial systolic blood bacteria, that are often associated to multiple pressure is between 70 and 100 mmHg organ failure. The last syndrome is the major dobutamine (2-20 microg/kg/min) improves cause of death with a mortality of about the contractility and reduces peripheral re- 40%65-68. Other frequent causes of ARDS sistances avoiding arterial vasoconstriction are: trauma, disseminated intravascular coag- (it acts only on beta receptors). If there are ulation (DIC), acute haemorrhagic pancre- signs of , dopamine (5-15 atitis, aspiration of gastric contents, inhala- microg/kg/ min) increases the contractility tion of foreign bodies, acute radiation pneu- and improve the arterial blood pressure, monitis, inhalation of toxic gases (smoke, acting both on alpha and beta peripheral ozone, cadmion, chlorine, nitrogen dioxide) receptors and, at low dosage, on dopamin- or circulating foreign substances (alloxan, al- ergic receptors in the renal glomerule pro- pha-naphthyl thiourea). Special forms of moting diuresis. ARDS are showed in the table below69 Oxygen could be administered with face (Table VII). 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 Table VII. Special forms of ARDS. is developing with modality of CPAP. CPAP has been shown to be effective in patients Pharmaceutical Narcotic overdose with cardiogenic pulmonary oedema who re- Chemotherapy main hypoxic despite maximal medical treat- Salicylate intoxication ment (Grade of recommendation B)10,59-62. Hydrochlorotiazide CPAP permits higher inspired oxygen con- Contrast fluid tent, increases mean airway pressure and im- Calcium antagonists overdose High altitude proves ventilation recruiting collapsed areas Neurogenic of the lung. Pulmonary embolism ARDS is defined by non cardiogenic pul- Eclampsia monary oedema, characterized by severe hy- Post cardioversion poxemia, new bilateral pulmonary infiltrates Post anesthesia Post cardiopulmonary bypass at radiography, without elevated left atrial

143 P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Management Clinical Manifestation The main life threatening problem of The clinical definition of common acquired ARDS is hypoxemia, that should be alleviat- pneumonia includes such typical signs and ed by recruiting and ventilating collapsed symptoms of lower respiratory tract infection, alveolar spaces and reducing the shunt. Hy- shared by both pneumonia and acute exacer- poxemia cannot be corrected by the simple bation of COPD. administration of oxygen. Mechanical venti- • Pleural pain, cough with purulent expec- lation via endotracheal intubation should be toration, dyspnoea, tachypnoea, and oth- initiated as soon as possible. PEEP improves er local symptoms; high fever or chills, oxygenation reducing the intrapulmonary headache, arthritis, muscular pain. shunt. In general 5 to 20 cm H2O provides a • New focal signs at the physical examina- reasonable balance among potential effects. tion of the chest. In fact the heterogeneity of lung damage, due to the different disposition of areas of consol- The chest radiography shows pleural effu- idation and atelectasis, causes that a certain sion, areas of consolidations and/or atelecta- amount of PEEP is appropriated in one re- sis. For the diagnosis of pneumonia, the pres- gion, too much in a normal region and too ence of an infiltrate or a consolidation in low in a more damaged region. The tradition- chest radiography is necessary. al ventilation included high flow with elevat- We define nosocomial pneumonia if it oc- ed tidal volume (12 ml/kg) and high plateau curs in patients admitted since at least 48 pressure (50 cm H2O), inducing ventilator-in- hours or discharged no more than 8 days be- duced lung injury. A low tidal volume (6 fore the onset of symptoms, or for outpa- ml/kg) and a low plateau pressure (max 30 tients or visitors that attended the hospital at cm H2O) decreased ARDS mortality from least during the past 48 hours. The most fre- 40% to 31%70-73. Several studies that provide quent pathogens are aerobi bacteria Gram support for the presence of endogenous glu- negative such as Enterobacter, Acinetobacter, cocorticoid inadeguacy in the control of in- Pseudomonas, Klebsiella, etc.; in the im- flammation and systemic inflammation-in- munocompromised patients most frequently, ducted peripheral glucocorticoid resistance in Staphylococcus aureus and Legionelle. Table ARDS74-78. Prolonged methylprednisolone VIII shows the risk factors for nosocomial administration (a loading dose of 2 mg/kg, pneumonia. followed by 2 mg/kg for 14 days, 1 mg/kg for The due to the en- the next 1 week, 0.5 mg/kg for the next 1 trance of fluids from stomach or upper respi- week, 0.25 mg/kg for the next 1 week and ratory tracts into the lower respiratory tracts, 0.125 mg/kg for the latest week, for a period can be classified in consideration of the three of 32 days at all) may accelerate the resolu- different pulmonary damages: toxic, obstruc- tion of both systemic inflammation and pe- tive or infective80. Table IX, from IDSA ripheral acquired glucocorticoid resistance in guidelines, shows in synthesis clinical mani- ARDS79. festations and therapeutic approach to the different forms. is defined for the b – Pneumonia unusual manifestations with majority of Pneumonia is defined as an inflammation systemic signs and symptoms (fever, of the lung parenchyma, of the respiratory tract distal to terminal bronchioli. The most frequent etiology is infective (Common Ac- quired Pneumonia), although there are five Table VIII. Risk factors for nosocomial pneumonia. different kinds of pneumonia: Elderly 1. Common acquired pneumonia; Severity of pathology 2. Nosocomial pneumonia; Admittance in ICU – endotracheal intubation 3. Aspiration pneumonia; Surgery 4. Atypical pneumonia; Previous use of antibiotics 5. Pneumonia in elderly.

144 Approach to respiratory failure in emergency department

Table IX.

Inoculum Pulmonary Clinical features Therapy

Acid Chemical 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 infection Usually insidious onset; cough, fever, Antibiotics bacterial purulent sputum; radiograph: infiltrate involving dependent pulmonary segment or lobe with or without cavitation

Inert fluids Mechanical Acute dyspnea; cyanosis with or without Tracheal suction: obstruction: reflex apnea; pulmonary edema intermittent positive airway closure pressure breathing with oxygen and isoproterenol Particulate Mechanical Dependent on level of obstruction, Extraction of particulate matter obstruction ranging from acute apnea and rapid matter, antibiotics for death to irritating chronic cough with superimposed infection or without recurrent infections

Modified from IDSA guidelines for CAP.

arthralgias, headache, etc.) and a poor pul- (need for mechanical ventilation, an increase monary and chest manifestations (cough in the size of infiltrates by > 50% within 48 h, without purulent sputum, no signs of con- or the need of vasopressors for > solidation at chest radiography). The more 4 hours, and acute renal failure), or two mi- frequent agents involved are Chlamydia nor criteria (respiratory rates > 30 breaths pneumoniae, Mycoplasma pneumoniae, per minute, PaO2/FiO2 < 250, bilateral/multi- Chlamydia psittaci, Coxiella burnetii. Sever- , arterial blood pressure al studies have shown that clinical, labora- 90/60 mmHg). The BTS rule is based on the tory and radiographic features cannot reli- presence of 2 main risk factors; if only one is ably differentiate between different present clinician should evaluate pre-existent causative pathogens81. The diagnosis of comorbidities (age more that 50 years, con- Chlamydia pneumoniae is made serologi- gestive –Ib-, ictus –Ib-, coronary cally or by polymerase chain reaction tech- artery disease –III-, diabetes mellitus –Ia-, niques; both Chlamydia and Mycoplasma neoplasm –Ib). There are 4 prognostic nega- are relatively often detected in mixed infec- tive factors: mental Confusion non pre-exis- tions with Streptococcus pneumoniae and tent, Urea > 7 mmol/l, Respiratory rate > 30 Haemophilus influenzae, thus making diffi- breaths/min, systolic Blood pressure < 90 (or cult to define under what circumstances diastolic < 60 mmHg) (CURB). they could be considered the cause of pneu- monia. Treatment is often empiric (Grade Management of recommendation A II): macrolide, doxi- If oxygen blood parzial pressure is less cyclin, and ciprofloxacin (Grade of recom- than 70 mmHg, oxygen should be adminis- mendation B III). tered to obtain an increasing in saturation The first step in a patient with a diagnosis major that 90%. If obstructive pulmonary of pneumonia is to assess the severity of ill- diseases don’t coexist, the inspiration fraction ness and the need for hospital admission that of O2 should be greater than 0.35. In serious- were identified by the American Thoracic So- ly ill patients, if oxygen therapy is not neces- ciety (ARS)82 and the British Thoracic Soci- sary to mantain saturation between 85 and ety (BTS) in 200183. The ATS rule is based on 90%, despite maximum medical treatment, the presence of at least one major criterion NIV could be used to improve oxygenation,

145 P. Forte, M. Mazzone, G. Portale, C. Falcone, F. Mancini, N. Gentiloni Silveri

Table X.

Modifying Guidelines factors/comments First choice Alternatives

Outpatients

ER LRTI# Aminopenicillin Tetracyclines, cephalosporins respiratory quinolones, macrolides Canadian No modifying factor Macrolide Doxycycline COPD, no recent antibiotics New macrolide Doxycycline or oral steroids COPD, antibiotics or oral Respiratory FQ Co-amoxiclav 2nd steroid within 3 months GEN cephalosporin + macrolide IDSA Doxycycline/macrolide/FQ+ CDC Macrolide/doxycycline/ Respiratory FQ cefuroxime//co-amoxiclav ATS No modifying factor New macrolide Doxycycline Cardiopulmonary disease β-Lactman + macrolide Respiratory FQ or other modifying factor or doxycycline

Hospital treated general ward

ERS β-Lactman + macrolide Canadian Respiratory FQ 2nd-4th GEN cephalosporin + macrolide IDSA β-Lactman + macrolide FQ CDC β-Lactman + macrolide FQ ATS No modifying factor Azithromycin i.v. β-Lactman + doxycycline or FQ alone Cardiopulmonary dis or β-Lactman + doxycycline FQ other modifying factor or macrolide

ICU-treatment

ERS 2nd-3nd GEN cephalosporin + macrolide or FQ + rifampicin Canadian P. aeruginosa not suspected Respiratory FQ + β-lactman β-Lactman + macrolide P. aeruginosa suspected Ciprofloxacin + antipseudomonas Antipseudomonas β-lactman or AG β-lactman + AG + macrolide IDSA P. aeruginosa not suspected Extended spectrum β-lactman + FQ or macrolide Structural lung disease Antipseudomonas β-lactman + ciprofloxacin CDC β-Lactman + macrolide or FQ Respiratory FQ ATS P. aeruginosa not suspected β-Lactman + macrolide or FQ P. aeruginosa suspected Antipseudomonas β-lactman + Antipseudomonas ciprofloxacin 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: fluoro- quinolone; 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 Approach to respiratory failure in emergency department

Table XI. Suggested strategy for empirical outpatients treatment of community acquired pneumonia in the immunocompe- tent adult. (Modified from Eur Respir J)84.

CAP

Clinical/epidemiological data No clinical/epidemiological data indicating indicating atypical pneumonia atypical pneumonia

Older, COPD and or Macrolide or doxycycline Younger and previously well other severe chronic ilness

Penicillin V or Amoxicillin ± amoxicillin clavulanic acid

Therapy failure Therapy failure

Macrolide or Doxycycline or doxycycline respiratory fluoroquinolone

Table XII. Suggested strategy for empirical inhospital treatment of community acquired pneumonia in the immunocompe- tent adult. (Modified from Eur Respir J)84.

Patient to moderate Probable pathogen Choice of empirical therapy CAP (cover required)

Mild to moderate CAP All cases Streptococcus pneumoniae Benzylpenicillin or amoxicillin clavulanic acid Cefotaxmeceftriaxone if high rate of hyghly penicillin-resistant pneumococci Chronic pulmonary disease Haemophilus influenzae and Co-amoxiclav, or 2nd/3rd generation or post-influenza pneumonia Moraxella catharralis cephalosporin (iv) Postinfluenza pneumonia Staphylococcus aureus 2nd/3rd generation cephalosporin (iv) and drug addied Epidemiological chemical Legionella Respiratory FQ, or macrolide + data data indicating legionella benzylpenicillin/amoxixillin clavulanic or 2nd/3rd generation cephalosporin (iv) Epidemiological clinical data Mycoplasma pneumoniae and Macrolide or doxycycline indicating other atypicals Chamydia pneumoniae Gram-negative cover nor routinely necessary (irrespective of patient’s age, or whether nursing home resident)97

Severe CAP All cases Streptococcus pneumoniae Cefotaxime ceftriaxone macrolide rifampicin Haemophilus influenzae, or benzylpenicilli respiratory FQ Moraxella catarrhalis, Staphylococcus aureus, “atypical” agents and Gram-negative enteric bacilli Pseudomanas aeruginosa need not be routinely

FQ: fluoroquinolone.

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