Approach to Respiratory Failure In

The second mechanism (mismatch in bloodgas exchanges) is due to the following differ-ent pathologies:

Adult acute respiratory distress syn-drome;

Neonatal respiratory distress syndrome; Acute cardiogenic pulmonary oedema; Severe status asthmaticus; Pneumonia; Airspace collapse (atelectasis); Pulmonary embolism.

The clinical signs and symptoms of patientswith ARF, refer to the two main manifesta-tions of pulmonary diseases: arterial hyper-capnia and hypoxemia.

The pathophysiology of hypercapnia isbased on four main mechanisms:

Increase in CO2 production (for istance,parenteral feeding with high doses of carbo-hydrates; high body temperature, etc.)

Deterioration in gas exchanges as the in-crease in alveolar death space ventilation (foristance in Chronic Obstructive PulmonaryDisease COPD , because of mismatch inventilation/perfusion ratio, and in pulmonaryembolism);

Deterioration in respiratory mechanicsthat involves a huge effort, an increase in res-piratory work and the development of a rapidshallow breathing CO2;

Alteration in the mechanism of control ofthe ventilation (for istance, in chronic hyper-capnia, we observe a decrease in ventilatorydrive with an increase in tolerance thresholdto CO2; it happens in metabolic alkalosistoo).

The hypoxemia is due to different patho-physiological mechanisms:

Hypoventilation; Alteration in gas diffusion;

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Abstract. Objectives and Background:The goal of this review is to provide update rec-ommendations that can be used by emergencyphysicians who provide primary cares to pa-tients with Acute Respiratory Failure (ARF), fromthe admission to an emergency departmentthrough the first 24 to 48 hours of hospitaliza-tion. This work wants to address the diagnosisand emergency medical care of ARF and themanagement of medical complications.

State of the Art: A lot of statement has beendeveloped for the early management and treat-ment of ARF; moreover, over the last fifteenyears, we have assisted to the rise of a newtechnique of ventilation, in the Emergency De-partment: Non Invasive Ventilation. This kind ofventilation was firsthy applied in Intensive Careand in Respiratory Care Unit. Randomized con-trolled clinical trials have showed its usefulnessin 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 de-fined as the inability of the respiratory systemto exchange gases and to oxygenate the bloodadequately1-8. We can distinguish two mecha-nisms at the basis of ARF:

1. Failure in pulmonary ventilation (pumpfailure);

2. Failure in gas exchanges (lung failure).

The first one is due to neuromuscular dis-eases, chest wall deformities, obstructive pul-monary diseases (Table I).

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)

Corresponding author: [email protected]; [email protected]

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Mismatch in ventilation/perfusion ratio; Pulmonary shunt.

Which are the clinical signs and symptomsof hypoxemia and hypercapnia? The first oneshows with shortness of breath, tachycardia,mental confusion, changes of personality,restlessness, cyanosis, hyper/hypotension, ar-rhythmias and palpitations. Hypercapnia, in-stead, shows with sleepiness, mental confu-sion, cephalea, convulsions, arrhythmias,miosis, papilledema, peripheral vasodilation,hypotension and coma.

The first goal of the initial diagnostic eval-uation is to understand the underling causes,and so to do differential diagnosis among allpathologic conditions that showed the mostimportant clinical symptom of this illness:dyspnoea.

A Approach to Patients with Dyspnoea

Clinical EvaluationA patient with ARF usually presents with

signs of respiratory distress: dyspnoea,cyanosis, tachypnea, accessory muscle use,paradoxical breathing and tachycardia. Pri-mary care physician must apply the algorithmA-B-C-D, in order to exclude an Acute Up-per Airway Obstruction (AUAO), first of all,and then he must operate as following:

1. He has to administer high flows of oxy-gen, to measure blood pressure, to takeheart rate, respiratory rate, oxygen satu-ration, to make an electrocardiogram.

Moreover he has to take an arterial bloodgas sample and a peripheral venous bloodsample to evaluate CK, CKMB, T-tropo-nine, LDH, AST, ALT and hemochrome.

2. At the same time he must evaluate theneurological state, in order to call for theresuscitator if Kelly score (Table II) ismore than 3.

3. If neurological state is not compromisedpatient can be managed by emergencyphysician, entirely. Arterial blood gas(ABG) evaluation: Hypoxemia with hypercapnia pump

failure due to neuromuscular disease orchest wall deformities; Lung failure dueto COPD or acute asthmatic status.

This last situation can be treated withpharmacological therapy and/or withnon invasive ventilation, if indicated. Pa-tient must undergo endotracheal intuba-tion (ETI) if his clinical conditions dete-riorate. Hypoxemia with no hypercapnia

lung failure due to ARDS or cardio-genic pulmonary oedema or pulmonaryembolism or pulmonary infection. Ifoxygen saturation in more than 90%continue to administer O2 with facemask and high flows. If oxygen satura-tion is less than 90% consider the useof Non Invasive Ventilation (NIV), to-gether with medical therapy.

4. Clinical evaluation must be associatedwith radiological evaluation (Chest X-Rays) and with continuous ABG evalua-tions (after 1 hour and after each chang-ing in clinical conditions). Patient mustundergo endotracheal intubation if hisclinical conditions deteriorate.

Evidence and Information SourcesA comprehensive literature search was

performed in order to select the latest rec-

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

Neuromuscular Drugs abusediseases Cervical tetraplegia

Curare/strychnine/phosphate poisoning

Guillaine-Barr syndrome Miastenia gravis; hereditary/acquired myopathies

Botulism/PoliomyelitisChest wall deformities Bilateral or hypertensive

PneumothoraxPneumomediastinum Post-traumatism

Obstructive diseases Severe Status AsthmaticusCentral airways obstruction

Table I.

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

Table II. Kelly scale.

ommendations for the early diagnosis andthe therapy of the pathologies below.

In developing of the present guidelines weconsidered the latest evidences in the man-agement of dyspnoea, asthma, COPD, ARDSand we applied the ATS Consensus Confer-ence indications9 and the BTS guidelines10 forthe use of NIV in ARF.

B Approach to Patients withAcute 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 pre-sents inspiratory stridor, because of the col-lapse of upper extra thoracic airways, duringthe inspiration when tracheal pressure is mi-nor than atmospheric one. The intra thoracicone that presents expiratory stridor, becausethe extrathoracic airways collapse during theexpiration, when the intrapleural pressure isgreater than atmospheric one.

The stridor is the main symptom ofAUAO (Table IV), and its often associatedwith cyanosis, loss of consciousness, napeshyperextension (especially in the epiglottidi-tis), trismus (especially in the peritonsillar ab-scess), dysphagia (severe epiglottiditis or pha-

ryngeal obstruction). We usually observeasymmetries in diaphragmatic ranges, in res-piratory movements, in the intercostal andsupraclavicular re-entrances.

If the physician suspects an epiglottiditis, heshould be cautious in carrying out clinical ex-amination: in fact he could provoke a com-plete obstruction stimulating with the tonguedepressor. Moreover, if respiratory distresscontinues and the patient is stable (rapid shal-low breathing, valid cough, conscious, lucidand alert patient but with no cardiovascular al-terations) physician should take blood pres-sure and oxygen saturation, continuously, andoften control ABG. If patient presents withrespiratory arrest he should follow the Ad-vanced Life Support Algorithm. In a secondtime physician should make differential diag-nosis between epiglottiditis and viral croup.

Anaphylaxis: if patients present with glot-tis oedema should be immediately intubatedbefore developing complete obstruction ofupper airways. Then they should be submit-ted to infusion therapy with adrenaline (1 mgin bolus repeatable), corticosteroids (hydro-cortisol methylprednisolone) at high doses,fluids.

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Infectious Viral laryngotracheitis (croup)Bacterial epiglottiditisBacterial tracheitis

Neoplasm Subglottic hemangioma Tracheal and endobronchial neoplasmsThyroid and mediastinal tumors

Traumatic External bodies aspirationAnaphylaxisObstructive Sleep Apnea Syndrome (OSAS)Neurogenic diseases Bilateral paralysis of recurrent nerve

Table III.

Modified by G. Garetto, La Nuova Medicina dUrgenza, Ed. C.G. Torino11.

Supraglottic Severe tonsillitis (> 10 years)Peritonsillar abscess (> 10 years)Retropharyngeal abscess (> 3 years)Epiglottiditis (3-7 years)

Subglottic Viral croup (3 months-3 years)Bacterial tracheitis

Table IV. Infectious AUAO.

138

Foreign bodies obstruction: do not intro-duce fingers into the oral cavity in order totake it out: it could slip down. If patient canspeak the physician could remove it with apowerful blow in the interscapular zone(from one to four powerful blows). Moreoverhe can try with Heimlichs manoeuvring. Thisone can be performed with supine patient, incase of loss of consciousness. If foreign bodycannot be still removed, patient should besubmitted to endoscopic removal, or tocricothyroidotomy, or to tracheostomy.

C Approach to Patients with ARFDue 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 isdue to hypoventilation with an increase inrespiratory work and rapid shallow breathing.Hypercapnia and hypoxemia associated withhypoventilation due to neuromuscular dis-eases are due to different mechanisms:

Muscular weakness; Decrease of pulmonary and thoracic

compliance; Increase in respiratory work; Decrease in central sensibility.

The clinical approach to these patientscould be differentiated on the base of theirconditions at the admission to the first aid.

Preserved and stable vital functions: if up-per airways are pervious, if there are no car-dio-vascular troubles and Kelly score is 1and patient presents only dyspnoea, deliveroxygen with facial mask and control arterialsaturation and blood pressure continuously.If arterial blood sample shows an oxygen sat-uration more than 90% and a PaCO2 lessthan 45 mmHg, evaluate ABG after 1 hourand control clinical conditions. Chest radiog-raphy should be done as soon as possible, tohelp the physician in differential diagnosisamong neuromuscular diseases, chest wall de-formities and brainstem pathologies.

Preserved But Instable Vital FunctionsCardio-circulatory arrest: ask for emer-

gency team and follow the algorithm ALS forthe cardiac arrest. Patient will be admitted tothe Intensive Care Unit (ICU).

D Approach to Patients withARF Due to COPD

The term COPD encompasses two well de-fined entities: emphysema and chronic bron-chitis. Emphysema is characterized by perma-nent and abnormal enlargement of airspace,distal to the bronchiole, associated to a de-struction of alveolar wall, without evident fi-brosis, and to an obstruction of distal lowerairway. Bronchitis is defined only by a clinicaldefinition as presence of cough and expecto-ration for more than three months per yearfor more than two consecutive years. The keyfeature that unites these diseases (bronchitisand emphysema) and the asthma (that weregoing to treat below) under the definition ofCOPD is the physiologic phenomenon of ob-struction to forced expiratory airflow.

COPD is a slowly progressive disease char-acterized by punctuated exacerbations two orthree times a year in patients with significantobstruction. It is identified by the presence ofairflow limitation that is not fully reversibleand does not change markedly over severalmonths. The disease is predominantly causedby smoking. The exacerbation, in most casesits due to infections, especially bacterial in-


Chest wall deformities KyphoscoliosisObesity-Hypoventilation syndrome

Fibrothorax-ThoracoplasticAnkylosing spondylitisBilateral diaphragmatic paralysis

Wandering costal flapNeuromuscular diseases

Table V. Infectious AUAO.

fections (level II of evidence)12. Thepathogens most often involved in COPD ex-acerbations are Haemophilus influenzae,Streptococcus pneumoniae, Moraxella ca-tarrhalis13,14; less often, gram negative bacte-ria, Chlamydia pneumoniae and Mycoplasmapneumoniae. Among viruses have been iden-tified: Rhinovirus, Influenza virus, Parain-fluenza virus, Coronavirus, Respiratory Syn-cytial Virus, Adenovirus. The cause of exac-erbation may be unidentifiable up to 30% ofexacerbation15.

Clinical EvaluationThe diagnosis of the exacerbations is clini-

cal and is based on three parameters: increas-ing in sputum production, purulent expecto-ration, worsening dyspnoea. There is a severi-ty scale for exacerbations based on thesefindings16: type 1 (severe exacerbations) haveall of the above symptoms; type 2 (moderateexacerbations) present only two of the threesymptoms; type 3 (mild exacerbations) pre-sent only one of the symptoms but associatedwith one of the following at least: an upperrespiratory tract infection in the past fivedays, fever, increasing in cough or wheezing,increasing in respiratory rate or in the heartrate by 20% above the baseline.

Each patient ranks the importance of dif-ferent symptoms individually, howeverbreathlessness is the most significance symp-tom. Individual symptoms are not useful inmaking or excluding the diagnosis of COPD(level IV of hierarchy)15.

Additional Diagnostic TestsChest radiography: some observational

studies showed substantial rate of chest radi-ograph abnormalities. However, chest radiog-raphy is not routinely necessary during exac-erbations, neither for the diagnosis (level ofhierarchy IV). It could be useful if there isthe suspect of pneumonia, or pneumothoraxor aspiration (such as in neuromuscolar dis-eases), or if patient is non-responsive to thetherapy. As chest radiography can sometimereveal a parenchymatous pulmonary lesionsuch as tuberculosis or bronchial carcinoma,patients who have not had a radiography pri-or to the exacerbation should obtain one12.

Spirometry: spirometric assessment, at thetime of presentation, or during the course oftreatment, is not useful in judging severity or

guiding management of patients with acuteexacerbation of COPD (level of hierarchyIV). Spirometry, however, is fundamental tomaking diagnosis of COPD because is the on-ly accurate method of measuring the airflowobstruction in patients. It cannot contributesto the severity of COPD (level of hierarchyIV) or distinguish asthma from COPD; it is apoor predictor of disability and quality of lifein COPD (level of hierarchy IV)17; it predictsprognosis of patients (level of hierarchyIV)18,19.

Serological Assays Are Only of Epidemiological Value

Sputum samples for microbiological tests(using Gram stain and culture) is indicated inseriously ill patients, if sputum is persistentlypresent and purulent, or if there is a historyof prior treatment failure (level of hierarchyIV).

Arterial blood gas sample is necessary toassess the severity of exacerbation and forthe initial management of the patient. More-over, patients who have low PaO2, highPaCO2, low pH are more likely to relapsewithin 14 days of initial presentation.

ECG and/or Echocardiogram is useful toassess cardiac status if there are features ofcor pulmonale (level of hierarchy IV).

CT scan of the thorax is necessary in sus-pect of pulmonary embolism. It is useful (lev-el of hierarchy IV) to investigate symptomsthat seem disproportionate to the spirometricimpairment, to investigate some suspect ab-normalities in chest radiograph.

Reversibility testing: there is a consider-able variability in change in FEV1 in responseto the same stimulus from day to day, so it isvirtually impossible to interpret the responseto an individual reversibility test unless theresponse is very large (an increase in FEV1more than 400 ml). Reversibility testing is notrecommended in the latest guideline pro-duced jointly by the American Thoracic Soci-ety and the European Respiratory Society.

Referral for specialist advice: these aremade when clinically indicated, at all stagesof disease, not only in the most severely dis-abled patients (level of hierarchy IV).

Need of Hospital ManagementMost patients with acute exacerbation of

COPD can be managed at home, but some of

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them need hospital treatment. This may bebecause of the following reasons:

Need for therapies that are not availableat home (such as non invasive ventila-tion);

Severe breathlessness; Poor/deteriorating general conditions; Cyanosis; Worsening peripheral oedemas; Impaired neurological conditions, men-

tal confusion; Acute onset; Significant comorbility particularly for

heart diseases; Changes in chest radiograph; Significant alteration in arterial blood

gas analysis (PaO2 < 60 mmHg; pH 110 beats per minute;

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4. Respiratory rate > 30 breaths per minute;5. Arterial saturation less than 90%.

This clinical features are associated with aforced expiratory volume or a peak expirato-ry flow rate less than 50%. In fact the sinequa non of an episode of acute asthma is thereversible, non uniform increase in airwayobstruction that induces diminished flow rate,hyperinflation of the lung and premature air-way closure. Moreover with the increase inwork of breathing and in expiratory effort thedynamic hyperinflation rises and auto-posi-tive end expiratory pressure (PEEP) devel-ops.

Arterial blood gas examination: it typicallyshows hypoxemia, hypocapnia, respiratory al-kalosis46-50. The more severe is the attack, thelower is the arterial oxygen saturation. How-ever most asthmatic patients dont developmarked hypoxemia and, also in severe at-tacks, its very infrequent that oxygen tensiondecrease under 50 mmHg. Respiratory acido-sis follows hypercapnia. With extreme flowlimitation metabolic acidosis develops. Infact, if cardiac output is compromised devel-ops lactic acidosis because of the hypoperfu-sion of peripheral tissue; in addition the in-creased oxygen consumption by respiratorymuscles also contributes. It may also be in-duced by aggressive administration of non se-lective sympathomimetics51.

Managements In hospital settings for asthmatic patients

the driving gas should be oxygen for acute illpatients. Moderately short-acting beta2-adrenergic agonists such as salbutamol andterbutaline have rapid onset of action andprovide more bronchodilation than domethylxanthines and anticholinergics, makingthem the first line treatment for acute illness.Adult patients with acute asthma should begiven 2.5-5 mg of salbutamol or 5-10 mg ofterbutaline (Grade of recommendation B23.There is evidence that additional benefit canbe obtained by adding anticholinergic treat-ment such as ipratropium bromide 500 mi-crog (Grade of recommendation A). Treat-ment should be repeated if patient is non re-sponsive to the therapy. In near fatal asthma,the use of intravenous salbutamol (5 mi-crog/min) and adrenaline (1 mg repeatablefor three times each 15 minutes), is effective.

Nebulized corticosteroids have been usedas a substitute of oral corticosteroids in mod-erate exacerbations of adult asthma; theyhave been shown to have an oral steroid spar-ing effect (Grade of recommendation A)23.Patients that are resistant or slowly respon-sive to beta-agonists need corticosteroidsmore urgently52-56. Methylprednisoloneshould be administered at dosage of 1 mg/kgof body weight during the acute attack. TheUS guidelines recommend 120-180 mg dailyof methylprednisolone given intravenously(in three or four doses). It must be repeatedfor 48 hours in those admitted, followed by60-80 mg/day until the FEV1 reach the 70%of normal. Oral prednisone (60 mg/day) canbe substituted57.

Methylxanthines, althought may have anti-nflammatory properties, are considerably lesseffective than the sympathomimetics andproduce more significant side effects23-46.

Compared to COPD, insufficient evidenceexists to recommend the use of NIV for asth-ma patients; there is also insufficient evi-dence to recommend Continuous PositiveAirway Pressure (CPAP) in acute asthma(Grade of recommendation C). The role ofNIV is not yet clear established57 and it coulddelay the use of endotracheal intubationwhen it is necessary.

E Approach to Patients with Hypoxemic ARF

a Pulmonary OedemaThe definition of pulmonary oedema is

the overflow of fluid from the lungs capillaryto the alveolar spaces. We can distinguish twodifferent entities of this pathology: cardio-genic pulmonary oedema and non-cardio-genic pulmonary oedema also called ARDS(Acute Respiratory Distress Syndrome), thatcan be distinguished by clinical signs and in-strumental examinations, although they pre-sent the same clinical symptoms.

The acute cardiogenic pulmonary oedemais a hydrostatic oedema due to an impairedfunction of left ventricle caused by coronaryartery disease, myocarditis, cardiomyopathy,hypertension, congenital heart diseases. It oc-curs when the pulmonary capillary pressurerises to value exceeding plasma colloid-os-


motic pressure (approximately 25 mmHg).Clinical examination reveals a low flow statewith wet crackles, jugular venous distention,third tone (S3 gallop), cardiomegaly. Con-cerning laboratory tests, ECG could showssigns of ischemia or infarction. There couldbe an increasing in cardiac enzymes and, atthe radiography, perihilar distribution ofoedema and the appearance of Kerley lines.Pulmonary capillary wedge pressure exceeds18 mmHg.

The treatment of acute pulmonary oedemais based on the use of oxygen, nitrates, diuret-ics and, if coexists cardiogenic shock, in-otropes.

Furosemide and nitrates (10 microg/min)are the first line of medical treatment andshould be administered, together with mor-phine, if arterial systolic blood pressure ex-ceed 100 mmHg. They promote diuresisand vasodilation and so act both on thepre-load and on the post-load of the heart,reducing cardiac work and improving theejection fraction. If arterial systolic bloodpressure is between 70 and 100 mmHgdobutamine (2-20 microg/kg/min) improvesthe contractility and reduces peripheral re-sistances avoiding arterial vasoconstriction(it acts only on beta receptors). If there aresigns of cardiogenic shock, dopamine (5-15microg/kg/ min) increases the contractilityand improve the arterial blood pressure,acting both on alpha and beta peripheralreceptors and, at low dosage, on dopamin-ergic receptors in the renal glomerule pro-moting diuresis.

Oxygen could be administered with facemasks with Venturi system or with reservoirto reach high concentration of oxygen until100%. During the last ten years the use ofNIV for treatment of acute pulmonary edemais developing with modality of CPAP. CPAPhas been shown to be effective in patientswith cardiogenic pulmonary oedema who re-main hypoxic despite maximal medical treat-ment (Grade of recommendation B)10,59-62.CPAP permits higher inspired oxygen con-tent, increases mean airway pressure and im-proves ventilation recruiting collapsed areasof the lung.

ARDS is defined by non cardiogenic pul-monary oedema, characterized by severe hy-poxemia, new bilateral pulmonary infiltratesat radiography, without elevated left atrial

pressure. The American - European Consen-sus Conference on ARDS defined the severi-ty of the pathology by the ratio ofPaO2/FiO2: a ratio of 300 or less defines theacute lung injury (ALI); a ratio of 200 or lessdefines ARDS regardless of the amount ofPEEP needed to support oxygenation63. Thepathogenesis is due to the lung damage, thatcauses an increasing in permeability of capil-lary endothelium and an alteration of lungalveolar-capillary barrier with overflow offluid into the alveolar and interstitial space,without increasing in pulmonary circulatorypressure. The damage involves both the en-dothelial and epithelial surface; the activatedendothelium participates and partly drivesthe neutrophil inflammatory response thatcontributes to edema formation and fibro-sis64. The most common cause of ARDS is asevere infection and it accounts for approxi-mately half of cases. It could present as a lo-calized or systemic disease and the mostcommon agents involved are gram-negativebacteria, that are often associated to multipleorgan failure. The last syndrome is the majorcause of death with a mortality of about40%65-68. Other frequent causes of ARDSare: trauma, disseminated intravascular coag-ulation (DIC), acute haemorrhagic pancre-atitis, aspiration of gastric contents, inhala-tion of foreign bodies, acute radiation pneu-monitis, inhalation of toxic gases (smoke,ozone, cadmion, chlorine, nitrogen dioxide)or circulating foreign substances (alloxan, al-pha-naphthyl thiourea). Special forms ofARDS are showed in the table below69(Table VII).

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Pharmaceutical Narcotic overdoseChemotherapySalicylate intoxicationHydrochlorotiazideContrast fluidCalcium antagonists overdose

High altitudeNeurogenicPulmonary embolism EclampsiaPost cardioversionPost anesthesiaPost cardiopulmonary bypass

Table VII. Special forms of ARDS.

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ManagementThe main life threatening problem of

ARDS is hypoxemia, that should be alleviat-ed by recruiting and ventilating collapsedalveolar spaces and reducing the shunt. Hy-poxemia cannot be corrected by the simpleadministration of oxygen. Mechanical venti-lation via endotracheal intubation should beinitiated as soon as possible. PEEP improvesoxygenation reducing the intrapulmonaryshunt. In general 5 to 20 cm H2O provides areasonable balance among potential effects.In fact the heterogeneity of lung damage, dueto the different disposition of areas of consol-idation and atelectasis, causes that a certainamount of PEEP is appropriated in one re-gion, too much in a normal region and toolow in a more damaged region. The tradition-al ventilation included high flow with elevat-ed tidal volume (12 ml/kg) and high plateaupressure (50 cm H2O), inducing ventilator-in-duced lung injury. A low tidal volume (6ml/kg) and a low plateau pressure (max 30cm H2O) decreased ARDS mortality from40% to 31%70-73. Several studies that providesupport for the presence of endogenous glu-cocorticoid inadeguacy in the control of in-flammation and systemic inflammation-in-ducted peripheral glucocorticoid resistance inARDS74-78. Prolonged methylprednisoloneadministration (a loading dose of 2 mg/kg,followed by 2 mg/kg for 14 days, 1 mg/kg forthe next 1 week, 0.5 mg/kg for the next 1week, 0.25 mg/kg for the next 1 week and0.125 mg/kg for the latest week, for a periodof 32 days at all) may accelerate the resolu-tion of both systemic inflammation and pe-ripheral acquired glucocorticoid resistance inARDS79.

b PneumoniaPneumonia is defined as an inflammation

of the lung parenchyma, of the respiratorytract distal to terminal bronchioli. The mostfrequent etiology is infective (Common Ac-quired Pneumonia), although there are fivedifferent kinds of pneumonia:

1. Common acquired pneumonia;2. Nosocomial pneumonia;3. Aspiration pneumonia;4. Atypical pneumonia;5. Pneumonia in elderly.

Clinical Manifestation The clinical definition of common acquired

pneumonia includes such typical signs andsymptoms of lower respiratory tract infection,shared by both pneumonia and acute exacer-bation of COPD.

Pleural pain, cough with purulent expec-toration, dyspnoea, tachypnoea, and oth-er local symptoms; high fever or chills,headache, arthritis, muscular pain.

New focal signs at the physical examina-tion of the chest.

The chest radiography shows pleural effu-sion, areas of consolidations and/or atelecta-sis. For the diagnosis of pneumonia, the pres-ence of an infiltrate or a consolidation inchest radiography is necessary.

We define nosocomial pneumonia if it oc-curs in patients admitted since at least 48hours or discharged no more than 8 days be-fore the onset of symptoms, or for outpa-tients or visitors that attended the hospital atleast during the past 48 hours. The most fre-quent pathogens are aerobi bacteria Gramnegative such as Enterobacter, Acinetobacter,Pseudomonas, Klebsiella, etc.; in the im-munocompromised patients most frequently,Staphylococcus aureus and Legionelle. TableVIII shows the risk factors for nosocomialpneumonia.

The aspiration pneumonia due to the en-trance of fluids from stomach or upper respi-ratory tracts into the lower respiratory tracts,can be classified in consideration of the threedifferent pulmonary damages: toxic, obstruc-tive or infective80. Table IX, from IDSAguidelines, shows in synthesis clinical mani-festations and therapeutic approach to thedifferent forms.

Atypical pneumonia is defined for theunusual manifestations with majority ofsystemic signs and symptoms (fever,


ElderlySeverity of pathologyAdmittance in ICU endotracheal intubationMechanical ventilationSurgery Previous use of antibiotics

Table VIII. Risk factors for nosocomial pneumonia.

arthralgias, headache, etc.) and a poor pul-monary and chest manifestations (coughwithout purulent sputum, no signs of con-solidation at chest radiography). The morefrequent agents involved are Chlamydiapneumoniae , Mycoplasma pneumoniae ,Chlamydia psittaci, Coxiella burnetii. Sever-al studies have shown that clinical, labora-tory and radiographic features cannot reli-ably differentiate between differentcausative pathogens81. The diagnosis ofChlamydia pneumoniae is made serologi-cally or by polymerase chain reaction tech-niques; both Chlamydia and Mycoplasmaare relatively often detected in mixed infec-tions with Streptococcus pneumoniae andHaemophilus influenzae, thus making diffi-cult to define under what circumstancesthey could be considered the cause of pneu-monia. Treatment is often empiric (Gradeof recommendation A II): macrolide, doxi-cyclin, and ciprofloxacin (Grade of recom-mendation B III).

The first step in a patient with a diagnosisof pneumonia is to assess the severity of ill-ness and the need for hospital admission thatwere identified by the American Thoracic So-ciety (ARS)82 and the British Thoracic Soci-ety (BTS) in 200183. The ATS rule is based onthe presence of at least one major criterion

(need for mechanical ventilation, an increasein 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 mi-nor criteria (respiratory rates > 30 breathsper minute, PaO2/FiO2 < 250, bilateral/multi-lobar pneumonia, arterial blood pressure90/60 mmHg). The BTS rule is based on thepresence of 2 main risk factors; if only one ispresent clinician should evaluate pre-existentcomorbidities (age more that 50 years, con-gestive heart failure Ib-, ictus Ib-, coronaryartery disease III-, diabetes mellitus Ia-,neoplasm Ib). There are 4 prognostic nega-tive factors: mental Confusion non pre-exis-tent, Urea > 7 mmol/l, Respiratory rate > 30breaths/min, systolic Blood pressure < 90 (ordiastolic < 60 mmHg) (CURB).

Management If oxygen blood parzial pressure is less

than 70 mmHg, oxygen should be adminis-tered to obtain an increasing in saturationmajor that 90%. If obstructive pulmonarydiseases dont coexist, the inspiration fractionof O2 should be greater than 0.35. In serious-ly ill patients, if oxygen therapy is not neces-sary to mantain saturation between 85 and90%, despite maximum medical treatment,NIV could be used to improve oxygenation,

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Table IX.

Modified from IDSA guidelines for CAP.

Inoculum Pulmonary Clinical features Therapy

Acid Chemical Acute dyspnea, tachypnea, tachycardia with Positive-pressurepneumonitis or with-out cyanosis bronchospasm, fever, breathing IV fluids,

sputum: pink, frothy; radiograph: infiltrates tracheal suctionin one or both lower lobes, hypoxemia

Oropharyngeal Bacterial infection Usually insidious onset; cough, fever, Antibioticsbacterial 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 isoproterenolParticulate 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 infectionor without recurrent infections

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Table X.

ERS: European Respiratory Society; IDSA: Infection Diseases Society of America; CDC: Center for DiseaseControl and Prevention; ATS: American Thoracic Society; LRTI: lower respiratory tract infection; FQ: fluoro-quinolone; GEN: generation; P. aeruginosa: Pseudomonas aeruginosa; AG: aminoglycoside. #: no distinction wasmade between community-acquired pneumonia and other LRTIs; +: depending on local resistance situation andunderlying factors; : risk factors for penicillin-resistant pneumococci or Gram-negative bacteria; /: risk factorsfor penicillin-resistant pneumococci or Gram-negative bacteria, including nursing home patients.

ModifyingGuidelines factors/comments First choice Alternatives

Outpatients

ER LRTI# Aminopenicillin Tetracyclines, cephalosporins respiratory quinolones,macrolides

Canadian No modifying factor Macrolide DoxycyclineCOPD, no recent antibiotics New macrolide Doxycyclineor oral steroids

COPD, antibiotics or oral Respiratory FQ Co-amoxiclav 2ndsteroid within 3 months GEN cephalosporin +

macrolideIDSA Doxycycline/macrolide/FQ+CDC Macrolide/doxycycline/ Respiratory FQ

cefuroxime//co-amoxiclavATS No modifying factor New macrolide Doxycycline

Cardiopulmonary disease -Lactman + macrolide Respiratory FQor other modifying factor or doxycycline

Hospital treated general ward

ERS -Lactman + macrolideCanadian Respiratory FQ 2nd-4th GEN

cephalosporin +macrolide

IDSA -Lactman + macrolide FQCDC -Lactman + macrolide FQATS No modifying factor Azithromycin i.v. -Lactman + doxycycline

or FQ aloneCardiopulmonary dis or -Lactman + doxycycline FQother modifying factor or macrolide

ICU-treatment

ERS 2nd-3nd GEN cephalosporin +macrolide or FQ + rifampicin

Canadian P. aeruginosa not suspected Respiratory FQ + -lactman -Lactman + macrolideP. aeruginosa suspected Ciprofloxacin + antipseudomonas Antipseudomonas

-lactman or AG -lactman + AG + macrolide

IDSA P. aeruginosa not suspected Extended spectrum -lactman + FQ or macrolide

Structural lung disease Antipseudomonas -lactman + ciprofloxacin

CDC -Lactman + macrolide or FQ Respiratory FQATS P. aeruginosa not suspected -Lactman + macrolide or FQ

P. aeruginosa suspected Antipseudomonas -lactman + Antipseudomonasciprofloxacin -lactman + AG +

respiratory FQ ormacrolide

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

Clinical/epidemiological data indicating atypical pneumonia

Macrolide or doxycycline Younger andpreviously well

Older, COPD and orother severe chronic ilness

No clinical/epidemiological data indicatingatypical pneumonia

Therapy failure

C A P

Macrolide ordoxycycline

Doxycycline orrespiratory fluoroquinolone

Penicillin V oramoxicillin

Amoxicillin clavulanic acid

Therapy failure

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

FQ: fluoroquinolone.

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

Mild to moderate CAPAll cases Streptococcus pneumoniae Benzylpenicillin or amoxicillin clavulanic acid

Cefotaxmeceftriaxone if high rate of hyghlypenicillin-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 pneumoniaeGram-negative cover nor

routinely necessary(irrespective of patientsage, or whether nursing home resident)97

Severe CAPAll cases Streptococcus pneumoniae Cefotaxime ceftriaxone macrolide rifampicin

Haemophilus influenzae, or benzylpenicilli respiratory FQMoraxella catarrhalis,Staphylococcus aureus,atypical agents andGram-negative enteric bacilli

Pseudomanas aeruginosaneed not be routinely

148

reduce respiratory rate and lessen dyspnoea.Moreover, NIV can be used as an alternativeto tracheal intubation if patient became hy-percapnic (Grade of recommendation C)10.

Patients should have arterial systolic pres-sure > 90 mmHg and the diuresis (0.5-1ml/kg/hour).

The empirical antibiotic treatment recom-mended by international guidelines is sum-marized in Table X (from ERJ)84.

It differs between outpatients and inhospi-tal patients, and its based on severity of ill-ness and the most likely pathogen involved invarious patients categories (Table XI).

Most of the outpatients should be treatedwith monotherapy, most often with beta-lac-tam alone (amoxicillin clavulanic acid orsecond and third generation intravenouscephalosporin). If therapy fails, Mycoplas-ma and/or Chlamydia pneumoniae may beinvolved and so treatment with doxycicline/macrolide or fluoroquinolone should be ini-tiated (Table XII).

The inhospital patient should be treatedwithin 8 hours from the admittance, withempirical therapy (amoxicillin clavulanicacid or second and third generation intra-venous cephalosporin): it should not be de-layed while waiting for the results of theexaminations (hemocultures, culture ofsputum, first of all). If patient has structur-al lung disease Pseudomonas should be sus-pected: piperacilline, piperacilline-tazobac-tam, cefepime, imipenem, meropenemshould be administered. If aspiration pneu-monia is suspected, a therapy againstanaerobic bacteria should be initiated (betalactamic antibiotics plus inhibitor of betalactamase, clindamycin, metronidazol). IfPneumococcus is suspected, beta lactamicantibiotics plus inhibitor of beta lactamase(1 g each 6 hours), cefotaxime (1 g each 8hours), ceftriaxone (1 g each 24 hours)should be administered, or, if patient is al-lergic, fluoroquinolones or quinopristin/dalfoprist in, or st i l l l inezolid or van-comycine.

In general, it is important for efficacy, aswell as to avoid development of resistance,that high enough or frequent enough dosingis used rather than extending therapy for >7-10 days (except for treatment of the Le-gionnaires disease, where 2-3 weeks dura-tion is recommended).

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