Goldman's Cecil Medicine || Acute Respiratory Failure

CHAPTER 104 ACUTE RESPIRATORY FAILURE 629

a relatively sudden onset (from hours to days) and a substantial change from the patient’s baseline condition. Dysfunction of the respiratory system indi-cates that the abnormal gas exchange may be caused by abnormalities in any element of the respiratory system (e.g., a central nervous system abnormality affecting the regulation of breathing or a musculoskeletal thoracic abnormal-ity affecting ventilation; Chapter 83), in addition to abnormalities of the lung itself. The term respiration refers, in a broad sense, to the delivery of oxygen (O2) to metabolically active tissues for energy usage and the removal of carbon dioxide (CO2) from these tissues (Table 104-1). Respiratory failure is a failure of the process of delivering O2 to the tissues and/or removing CO2 from the tissues. Abnormalities in the periphery (e.g., cyanide poisoning, pathologic distribution of organ blood flow in sepsis) can also lead to tissue

104 ACUTE RESPIRATORY FAILURE LEONARD D. HUDSON AND ARTHUR S. SLUTSKY

ACUTE RESPIRATORY FAILUREDEFINITION

Acute respiratory failure occurs when dysfunction of the respiratory system results in abnormal gas exchange that is potentially life-threatening. Each element of this definition is important to understand. The term acute implies

TABLE 104-1 ABBREVIATIONSCOMMONLYUSEDINACUTERESPIRATORYFUNCTION

ABG Arterial blood gas or arterial blood gas analysisALI Acute lung injuryARDS Acute respiratory distress syndromeARF Acute respiratory failurecm H2O Centimeters of waterCaO2 Content of oxygen in arterial bloodCCO2 Content of oxygen in end-capillary bloodCO2 Carbon dioxideCOPD Chronic obstructive pulmonary diseaseCPAP Continuous positive airway pressure (used when positive pressure

during exhalation is applied with spontaneous ventilation)CvO2 Content of oxygen in mixed venous bloodFIO2 Fraction of inspired oxygeng/dL Grams per deciliterHbO2 Saturation of hemoglobin by oxygenL/min Liters per minutemL/kg Milliliters per kilogrammL/min Milliliters per minutemm Hg Millimeters of mercuryNIPPV Noninvasive positive-pressure ventilationO2 OxygenP(A-a)O2 Difference of partial pressure of oxygen between mean alveolar gas and

arterial blood (alveolar-to-arterial oxygen difference)PACO2 Partial pressure of carbon dioxide in alveolar gasPaCO2 Partial pressure of carbon dioxide in arterial bloodPAO2 Partial pressure of oxygen in alveolar gasPaO2 Partial pressure of oxygen in arterial bloodPaO2/FIO2 Ratio of partial pressure of oxygen in arterial blood to fraction of

inspired oxygenPBW Predicted body weightPcCO2 Partial pressure of carbon dioxide in end-capillary bloodPcO2 Partial pressure of oxygen in end-capillary bloodPEEP Positive end-expiratory pressure (used when positive pressure during

exhalation is applied with mechanical ventilation)P/F PaO2/FIO2 ratioPIO2 Partial pressure of oxygen in inspired gasPO2 Partial pressure of oxygenPvCO2 Partial pressure of carbon dioxide in mixed venous bloodPvO2 Partial pressure of oxygen in mixed venous bloodQ Blood flow or perfusionRR Respiratory rateSaO2 Percentage of saturation of hemoglobin by oxygen in arterial blood�V Ventilation� �V Q Ventilation-to-perfusion ratio

VT Tidal volume


hypoxia; although these conditions represent forms of respiratory failure in the broadest terms, this chapter focuses on respiratory failure resulting from dysfunction of the lungs, chest wall, and control of respiration.

PATHOBIOLOGYAbnormal gas exchange is the physiologic hallmark of acute respiratory failure, which can be classified in several ways (Table 104-2). Although gas exchange can be abnormal for either oxygenation or CO2 removal, significant hypoxemia is nearly always present when patients with acute respiratory failure breathe ambient air. If CO2 is retained at a potentially life-threatening level, this is usually accompanied by significant hypoxemia (see later). The life-threatening aspect of the condition places the degree of abnormal gas exchange in a clinical context and calls for urgent treatment.

The diagnosis of acute respiratory failure requires a significant change in blood gases from baseline. Many patients with chronic respiratory problems can function with blood gas tensions that would be alarming in a physiologi-cally normal individual. Over time, these patients with so-called chronic respiratory failure or chronic respiratory insufficiency develop mechanisms to compensate for inadequate gas exchange. Conversely, this chronic condi-tion makes patients vulnerable to insults that could be easily tolerated by a previously healthy individual.

In acute respiratory failure, the O2 content in the blood (available for tissue use) is reduced to a level at which the possibility of end-organ dysfunction

increases markedly. The value of the partial pressure of O2 in the arterial blood (Pao2) that demarcates this vulnerable zone is the point of the oxyhe-moglobin dissociation relationship at which any further decrease in the Pao2 results in sharp decreases in the amount of hemoglobin saturated with O2 (Sao2) and in the arterial blood O2 content (Cao2). Although arbitrary, acute respiratory failure is often defined in practice as occurring when the Pao2 is less than 55 mm Hg (Fig. 104-1). In general, the locus on the curve that indicates the partial pressure at which O2 is being unloaded to the tissues is the most important determinant of how much O2 is available for the cells and their mitochondria. Usually, the ability to unload O2 at the tissue level more than compensates for small decreases in the amount of O2 picked up in the lungs when the oxyhemoglobin dissociation curve is shifted rightward. With a leftward shift in the curve, O2 is bound more tightly to hemoglobin, so less O2 is available for tissue delivery.

These clinical considerations imply that any definition of acute respiratory failure based on an absolute level of Pao2 is arbitrary. A healthy, young, con-ditioned individual climbing at high altitude may have a Pao2 of less than 50 mm Hg because of the reduction in inspired O2 pressure. This individual is not in acute respiratory failure, even though the Pao2 may be in the low 40s. A patient who has chronic obstructive pulmonary disease (COPD) and whose usual range of Pao2 is 50 to 55 mm Hg would not be considered to be in acute respiratory failure if the Pao2 was 50 mm Hg. However, if a patient’s usual Pao2 was 60 to 70 mm Hg, a Pao2 of 50 mm Hg would be associated

TABLE 104-2 SYSTEMSTOCLASSIFYACUTERESPIRATORYFAILUREHYPOXIC VERSUS HYPERCAPNIC-HYPOXIC ARF

Causes of Hypoxic ARFAcute lung injury/ARDSPneumoniaPulmonary thromboembolismAcute lobar atelectasisCardiogenic pulmonary edemaLung contusionAcute collagen vascular disease (Goodpasture’s syndrome, systemic lupus

erythematosus)

Causes of Hypercapnic-Hypoxic ARFPulmonary disease

COPDAsthma: advanced, acute, severe asthma

Drugs causing respiratory depressionNeuromuscular

Guillain-Barré syndromeAcute myasthenia gravis

Spinal cord tumorsMetabolic derangements causing weakness (including hypophosphatemia,

hypomagnesemia)Musculoskeletal

KyphoscoliosisAnkylosing spondylitis

Obesity hypoventilation syndrome (often with additional acute, superimposed abnormality as cause of ARF)

ETIOLOGIC MECHANISMS OF HYPOXEMIA

Normal P(A-a)O2*

↓PIO2

High altitude; inadvertent administration of low FIO2 gas mixtureHypoventilationSee causes of hypercapnic-hypoxic ARF above

Increased P(A-a)O2*

Ventilation-perfusion ( � �V Q ) mismatchAirway diseaseVascular disease, including pulmonary thromboembolism

ShuntAcute lung injury/ARDSPneumoniaParenchymal lung diseaseCardiogenic pulmonary edemaPulmonary infarction

Diffusion limitation†

ARF WITH AND WITHOUT CHRONIC LUNG DISEASE

With Chronic Lung DiseaseCOPDAsthmaParenchymal lung diseasesRestrictive lung/chest wall diseases

Without Chronic Lung Disease‡

Acute lung injury/ARDSPneumoniaPulmonary thromboembolism

ARF BY ORGAN SYSTEM INVOLVED

Respiratory (Lungs and Thorax)Airway/airflow obstruction

COPDAsthma

Pulmonary parenchymaPneumoniaAcute lung injury/ARDSAcute flare of chronic collagen vascular disease (e.g., Goodpasture’s syndrome,

systemic lupus erythematosus)

Central Nervous SystemRespiratory depression

Increased sedatives, tranquilizers with respiratory effect; opiates; alcoholBrain stem and spinal cord involvement

Tumors, trauma, vascular accidents

NeuromuscularGuillain-Barré syndromeMyasthenia gravis

CardiovascularCardiogenic pulmonary edemaPulmonary thromboembolism

Renal/EndocrineVolume overloadMetabolic abnormalities

*Calculated using the alveolar-air equation; see text for description.†See text for discussion.‡These can also be superimposed on chronic disease.ARDS = acute respiratory distress syndrome; ARF = acute respiratory failure; COPD = chronic obstructive pulmonary disease; Fio2 = fraction of inspired oxygen; P(A-a)o2 = alveolar-to-arterial oxygen difference; Pio2 = partial pressure of inspired oxygen; � �V Q = ventilation-to-perfusion ratio.


with a substantial risk for a further life-threatening reduction in oxygenation; this patient should be considered to have acute respiratory failure.

Traditionally, the level of arterial CO2 partial pressure (Paco2) that defines acute respiratory failure has been 50 mm Hg or greater, if accompanied by arterial acidosis with a pH of 7.30 or less. The Paco2 is linked to pH because it is generally thought that acidosis leads to tissue dysfunction and symptoms. Patients with severe COPD may have chronic CO2 retention, but renal com-pensation for the respiratory acidosis protects them against abnormalities related to the elevation in CO2. A further acute rise in Paco2 can precipitate symptoms and other organ dysfunction; however, even severe respiratory acidosis (pH 7.1) seems to be better tolerated than metabolic acidosis of the same pH in most previously healthy individuals if arterial and tissue oxygen-ation is adequate.

PathophysiologyFive mechanisms can lead to a reduction in Pao2: (1) decreased inspired partial pressure of O2 (Pio2) (e.g., at high altitude or when breathing a reduced percentage O2 mixture); (2) hypoventilation; (3) ventilation-perfusion ( � �V Q ) mismatch; (4) shunting of blood from the pulmonary to systemic circulation, bypassing the alveoli anatomically or functionally; and (5) abnormal diffusion of O2 from the alveoli into the capillary blood. In essence, a shunt is an extreme � �V Q mismatch in which blood perfuses alveoli with no ventilation; it is differentiated clinically from other � �V Q mismatching by the response to breathing supplemental O2 (see later).

For clinical purposes, diffusion abnormalities are not an important cause of hypoxemia at sea level because there is sufficient time for adequate diffu-sion of O2 during the transit of a red blood cell through the pulmonary capil-lary bed, even in the presence of severe lung disease. Even when diffusion abnormalities are present and contribute to hypoxemia, � �V Q mismatch and shunting nearly always coexist and are quantitatively more important causes of hypoxemia. Except at high altitude or when a subject is breathing a gas mixture low in O2, hypoventilation, � �V Q mismatch, and shunting are the dominant causes of acute respiratory failure.

If only hypoventilation is present, the resulting hypoxemia is associated with a normal difference between the calculated alveolar and the measured arterial oxygenation levels (P(A-a)o2). In this setting, an elevated Paco2 sug-gests disease processes that affect nonpulmonary respiratory function (e.g., central respiratory depression resulting from drug overdose, neuromuscular

diseases such as Guillain-Barré syndrome, or chest wall disease such as flail chest; Chapter 86). In contrast, � �V Q mismatch and shunting are associated with an elevated P(A-a)o2, which may or may not coexist with hypoventila-tion. The normal value for P(A-a)o2 varies as a function of the fraction of inspired O2 (Fio2), increasing as Fio2 increases.

When � �V Q mismatch or shunting is the cause of hypoxemia, some alveo-lar regions have increased PAco2 and reduced PAo2; the blood in the vessels perfusing these alveoli reflects these abnormal gas tensions. The increased PAco2 usually can be reversed by increasing overall ventilation, but hyper-ventilation does not correct the decreased Pao2.� �V Q mismatch is distinguished from shunting by assessing the Pao2

response to enhanced O2 administration. Hypoxemia caused by � �V Q mis-match can be corrected to a nearly complete O2 saturation of the hemoglobin in most patients by a relatively small increase in Fio2, such as from 0.24 to 0.28 by face mask or 1 to 2 L/minute O2 by nasal prongs, in patients with acute exacerbations of COPD. If the airways to poorly ventilated alveoli remain open and the enriched O2 mixture is administered for an adequate length of time (ranging from a few minutes to 20 minutes, depending on the degree of � �V Q inequality), the increased Pio2 is reflected by an increased PAo2 and an increased Pao2. When a shunt is present (no ventilation but continued perfusion), a relatively small increase in the Fio2 has little or no effect on the Pao2, and even large increases in Fio2 up to 1.0 result in only modest increases in Pao2 (Fig. 104-2).

CLINICAL MANIFESTATIONSThe hallmark of acute respiratory failure is the inability to maintain adequate oxygenation or the inability to maintain an appropriate Paco2. Patients are typically dyspneic and tachypneic, unless progressive respiratory failure causes fatigue—sometimes leading to respiratory arrest—or a drug overdose or neuromuscular condition prevents an appropriate respiratory response to hypoxia and/or the hypercapnic acidosis. Neurologic function may deterio-rate, and myocardial ischemia or even infarction may be precipitated by the hypoxemia. In addition, each cause has its own specific manifestations (see later).

DIAGNOSISAs part of the diagnosis of acute respiratory failure, the physician has three objectives: (1) confirm the clinical suspicion that acute respiratory failure is present, (2) classify the type of acute respiratory failure (e.g., hypoxemia caused by hypoventilation vs. hypoxemia caused by � �V Q mismatch or shunting), and (3) determine the specific cause (e.g., acute lung injury sec-ondary to sepsis or decompensated COPD because of acute bronchitis). Defining the type of acute respiratory failure and determining the specific cause are prerequisites to optimal management.

The initial approach to diagnosis consists of considering information from four sources: (1) clinical history and physical examination; (2) physiologic abnormalities, particularly arterial blood gas derangements, which help establish the pathophysiologic mechanisms of hypoxemia; (3) chest radio-graphic findings; and (4) other tests aimed at elucidating specific causes. In many cases, the clinical picture from the history is so clear that the presump-tive type of acute respiratory failure (and sometimes the cause) is obvious, so treatment can be started while confirmatory laboratory studies are ordered. In other cases, a clinician may be asked to see a patient because of an abnor-mal chest radiograph or abnormal arterial blood gases ordered by someone else and may elicit the pertinent history based on these clues. When the degree of hypoxemia is life-threatening, therapeutic decisions must be made quickly, even if data are limited. The clinician must obtain updated informa-tion continually and should view most therapeutic decisions as therapeutic trials, with careful monitoring to assess desired benefits and possible detri-mental effects.

Clinical EvaluationThe presentation often reflects one of three clinical scenarios: (1) the effects of hypoxemia and/or respiratory acidosis, (2) the effects of primary (e.g., pneumonia) or secondary (e.g., heart failure) diseases involving the lungs, and (3) the nonpulmonary effects of the underlying disease process. The clinical effects of hypoxemia and/or respiratory acidosis manifest mainly in the central nervous system (e.g., irritability, agitation, changes in personality, depressed level of consciousness, coma) and the cardiovascular system (e.g., arrhythmias, hypotension, hypertension) (Table 104-3). In patients with underlying COPD (Chapter 88) with a gradual onset of acute respiratory failure, central nervous system abnormalities may be the major presenting

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PaO2 (mm Hg)

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SaO

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FIGURE 104-1. Oxyhemoglobin association-dissociation curve. The axis for oxygensaturationinthearterialblood(SaO2)isontheleft,andtheaxisforarterialcontentofoxygen(CaO2)isontheright.CaO2isthesumoftheoxygendissolvedinplasma(denotedas“Dis-solved”inthefigure)plustheoxygenboundtohemoglobin.Atanormalhemoglobin,mostof the oxygen is carried in combination with hemoglobin, with only a relatively smallamountofoxygendissolved inplasma.Whenthevalueof thearterialpartialpressureofoxygen(PaO2) isonthe“flat”portionofthecurve(PaO2≥60to65mmHg,normalpartialpressure of carbon dioxide [PCO2], and normal pH), raising the PaO2 further has relativelylittleeffectontotaloxygencontent.Increasesintemperature,PCO2,hydrogenionconcen-tration,or2,3-diphosphoglyceratecausearightwardshift intheoxyhemoglobinassocia-tion-dissociationcurve.


•

• •

•

PaO2=41PaCO2=46

PaO2=117PaCO2=32

Valv=6.1

PaO2=105PaCO2=37

CvO2=11.9PvO2=32PvCO2=46

CcO2=14.8PcO2=41PcCO2=46


CaO2=16.9PaO2=50PaCO2=40





A

FIO2=0.21

PaO2=665PaCO2=48

PaO2=682PaCO2=31

PaO2=677PaCO2=36


CcO2=22PcO2=665PcCO2=48


CaO2=22PaO2=672PaCO2=40





B

FIO2=1.0

Valv=6.3 Valv=5.8

Valv=5.6

FIGURE 104-2. Arterial oxygenation. Comparison of theeffect on arterial oxygenation of increasing the fraction ofinspiredoxygen(FIO2)frombreathingambientair(FIO2=0.21)(A)andbreathing100%oxygen(FIO2=1.0)(B)withalowventilation-to-perfusion ratio ( � �V Q) (left) and a shunt (right), using a two-compartmentlungmodel.Shuntinganddecreased � �V Qcanleadto identical arterial blood gases (partial pressure of oxygen inarterial blood [PaO2] = 50mm Hg; partial pressure of carbondioxide in arterial blood [PaCO2]= 40mm Hg).The response tosupplemental oxygen administration is markedly different.Hypoxemiaisonlypartiallycorrectedbybreathing100%oxygenwhenashuntispresentbecausearterialoxygenationrepresentsan average of the end-capillary oxygen content (CCO2) fromvariouspartsofthelung,notanaverageofthepartialpressuresofoxygen(partialpressureofcarbondioxideintheend-capillaryblood[PcCO2]).WhentheCCO2valuesaremixed,thePaO2isdeter-minedfromtheresultantcontentofoxygeninthearterialblood(CaO2) by the oxyhemoglobin association-dissociation relation-ship(seeFig.104-1).Withlow � �V Q (asisoftenthecaseinpatientswithchronicobstructivepulmonarydisease),anincreaseinFIO2increasesthealveolarpartialpressureofoxygen(PO2)ofthelow� �V Q unitandleadstoamarkedincreaseinarterialPO2.ThevaluesinthisfigureweregeneratedfrommodelingtoresultinthesamePaCO2(40mmHg)forallfoursituationsshown;thisisthereasonforslightchangesinalveolarventilation( � �V Q alv)forsomeoftheconditions.Severalassumptionsaremade:(1)nodiffusionlimita-tion is present; (2) oxygen consumption= 300mL/minute, andCO2 production = 240mL/minute; (3) cardiac output = 6.0L/minute;(4)thelow � �V Q regionsintheleftpanelsrepresent60%ofthecardiacoutputperfusingalveoliwitha � �V Q 25%ofnormal;and (5) the shunts in the right panels represent a 37% shunt(i.e., 37% of the cardiac output is perfusing alveoli with noventilation).

TABLE 104-3 CLINICALMANIFESTATIONSOFHYPOXEMIAANDHYPERCAPNIA

HYPOXEMIA HYPERCAPNIATachycardia SomnolenceTachypnea LethargyAnxiety RestlessnessDiaphoresis TremorAltered mental status Slurred speechConfusion HeadacheCyanosis AsterixisHypertension PapilledemaHypotension ComaBradycardia DiaphoresisSeizuresComaLactic acidosis**Usually requires additional reduction in oxygen delivery because of inadequate cardiac output, severe anemia, or redistribution of blood flow.

findings. Cyanosis, which requires at least 5 g/dL of unsaturated hemoglobin to be detectable, may not be seen before serious tissue hypoxia develops, especially in patients with underlying anemia.

Pulmonary symptoms and signs often reflect the respiratory disease causing the acute respiratory failure. Examples include cough and sputum with pneumonia (Chapter 97) or chest pain from pulmonary thromboem-bolism with infarction (Chapter 98). Dyspnea and respiratory distress are nonspecific reflections of the respiratory system’s difficulty in meeting the increased demands from pulmonary and nonpulmonary diseases.

Physical findings may be associated with a particular pathologic lung process, such as pneumonia, causing bronchial breathing and crackles on auscultation, or the crackles (rales) of cardiogenic pulmonary edema (Chapter 58). Abnormal findings may be minimal or absent in patients with acute lung injury or pulmonary thromboembolism.

In some patients, the clinical picture is dominated by the underlying disease process, particularly with diseases that cause acute lung injury, such as sepsis (Chapter 108), severe pneumonia (Chapter 97), aspiration of gastric contents (Chapter 94), and trauma. In these conditions the physical examination is often nonspecific, with no obvious clues except, for example, fever with sepsis or pneumonia and hypotension with septic shock.

Assessment of Physiologic AbnormalitiesThe clinical suspicion of acute respiratory failure must be addressed by arte-rial blood gas analysis to answer several questions.1. Is hypoxemia present? The answer is based largely on the value of the Pao2

or Sao2, and the degree of the hypoxemia not only confirms the diagnosis of acute respiratory failure but also helps define its severity.

2. Is hypoventilation present? If the Paco2 is elevated, alveolar hypoventilation is present.

3. Does the degree of hypoventilation explain the hypoxemia? If the P(A-a)o2 is normal, hypoventilation explains the presence and degree of hypoxemia. In this case, the most likely causes of acute respiratory failure are central nervous system abnormalities and a chest wall abnormality. If the P(A-a)o2 is increased but hypoventilation does not explain the hypox-emia, another condition must be present; common diagnoses include COPD, severe asthma, and early-stage acute respiratory distress syndrome (ARDS).

4. If hypoxemia exists without hypoventilation, an elevated P(A-a)o2 should be confirmed, and the response to breathing an enhanced O2 mixture would answer this question: Is the increase in P(A-a)o2 the result of a � �V Q abnormality or of shunting? If hypoxemia is primarily the result

of a � �V Q abnormality, the likely cause is an airway disease, either COPD or acute severe asthma, or a vascular disease, such as pulmonary


thromboembolism. If shunting is the major explanation for the hypox-emia, processes that fill the air spaces (e.g., cardiogenic pulmonary edema, noncardiogenic pulmonary edema in acute lung injury or ARDS, or puru-lent pulmonary secretions in acute pneumonia) or, less commonly, an intracardiac or anatomic intrapulmonary shunt is the likely cause. Condi-tions that fill air spaces should be confirmed by an abnormal chest radio-graph; if the radiograph is normal, an intracardiac shunt should be considered and confirmed by echocardiography.

Chest RadiographyThe chest radiograph in acute respiratory failure is likely to show one of three patterns (Fig. 104-3): (1) normal (or relatively normal), (2) localized alveo-lar filling opacities, or (3) diffuse alveolar filling opacities. Diffuse interstitial opacities are also possible, but diseases that cause this pattern usually have a more gradual onset and are associated with chronic respiratory failure. If the chest radiograph is normal (i.e., it is clear or relatively clear), airway diseases, such as COPD and asthma, or pulmonary vascular diseases, such as throm-boembolism, are more likely. If a localized alveolar filling abnormality is present, pneumonia is the major consideration, but pulmonary embolism and infarction should also be considered. When diffuse (bilateral) alveolar filling abnormalities are present, cardiogenic pulmonary edema, acute lung injury (e.g., as seen in sepsis, trauma, or aspiration of gastric contents), and diffuse pneumonia are the major considerations. The combination of the chest radiograph and the arterial blood gas interpretation can be helpful. The finding of a significant shunt may suggest acute lung injury in a patient in whom this diagnosis was not clinically obvious; the chest radiograph should help to confirm that possibility.

Other EvaluationsAll patients with acute respiratory failure should have a complete blood count, including a platelet count; routine blood chemistry tests; prothrombin time; and urinalysis to screen for possible underlying causes and comorbid conditions. Other blood tests should be guided by the clinical picture. Exam-ples include a serum amylase level if pancreatitis is a possible cause of ARDS and thyroid indices if severe hypothyroidism is a possible cause of hypoven-tilation. Blood cultures are recommended whenever sepsis is suspected.

Any abnormal fluid collections, especially pleural effusion (Chapter 99), should be aspirated for diagnostic purposes. Sputum Gram stain and culture are indicated when pneumonia is suspected.

Other specific tests should be directed by the history, physical examina-tions, arterial blood gas levels, and chest radiograph. An abdominal com-puted tomography (CT) scan may be indicated to search for the source of infection in a patient with sepsis and acute lung injury. A chest CT scan may help define pulmonary disease if the chest radiograph is not definitive. A CT arteriogram of the pulmonary circulation may diagnose pulmonary throm-boembolism (Chapter 98). A head CT scan may be indicated if a stroke involving the respiratory center is suspected. Routine blood chemistry studies can detect diabetic ketoacidosis or renal failure as contributing causes.A

B

CFIGURE 104-3. Chest radiographs (left) and computed tomography (CT) scans (right) of the three most common findings in diseases causing acute respiratory failure.A,Rela-tively clear chest, consistent with an acute exacerbation of airway disease (e.g., asthma,chronic obstructive pulmonary disease) or a central nervous system or neuromusculardiseaseasthecauseofacuterespiratoryfailure.B,Localizedalveolarfillingopacity,mostcommonly seen with acute pneumonia. C, Diffuse bilateral alveolar filling opacitiesconsistentwithacutelunginjuryandacuterespiratorydistresssyndrome.TheCTscaninC shows a small left pneumothorax and cavities or cysts that are not apparent on theanteroposteriorchestradiograph.

General MeasuresThemanagementofacuterespiratoryfailuredependsonitscause,itsclini-

calmanifestations,andthepatient’sunderlyingstatus.Certaingoalsapplytoall patients: (1) improvement of the hypoxemia to eliminate or markedlyreducetheacutethreattolife,(2)improvementoftheacidosisifitisconsid-ered life-threatening, (3) maintenance of cardiac output or improvement ifcardiac output is compromised, (4) treatment of the underlying diseaseprocess,and(5)avoidanceofpredictablecomplications.

Theprecisemethodsforimprovinghypoxemiadependonthecauseoftheacute respiratory failure. An increase in the inspired O2 concentration is acornerstoneoftreatmentfornearlyallpatients,however.

Thelevelofacidosisthatrequirestreatmentotherthanfortheunderlyingdisease process is not clear. Although normalization of the arterial pH wassuggestedinthepast,respiratoryacidosisisapparentlywelltoleratedinmanypatientswithsevereARDS,soapatientwithapHof7.15orgreatermaynotrequire bicarbonate therapy. If the acidemia coexists with clinical complica-tions,suchascardiacarrhythmiasoradecreasedlevelofconsciousness,thathavenootherobviouscause,treatmentstoincreasepHshouldbeconsidered.Thetherapeuticgoalisalleviationorreductionoftheaccompanyingcompli-cationsbyimprovingthelevelofacidosis;itusuallyisnotnecessarytonormal-izethepH(Chapter120).

ThemaintenanceofcardiacoutputiscrucialforO2deliveryinacuterespira-toryfailure,especiallybecausemechanicalventilationandpositiveend-expi-ratory pressure (PEEP) may compromise cardiac output. Placement of apulmonaryarterycatheterallowsmeasurementofcardiacoutputandfillingpressures, but patients who have these catheters do no better than similarpatientsmanagedwithoutthem.1

Manytherapeutic interventions that improveshort-termphysiologicvari-ables may worsen long-term, clinically important outcomes. Transfusing allpatientstomaintainahemoglobingreaterthan10g/dLincreasesmortalityincriticallyillpatientswhohavenothadanacutemyocardialinfarctionanddonothaveunstableangina,eventhoughtheO2carryingcapacityofthebloodisacutelyincreased.Useofarelativelylargetidalvolume(e.g.,12mL/kgpre-dicted body weight, which is equivalent to approximately 10 to 10.5mL/kgmeasuredbodyweightinpatientswhoaresomewhatoverweight)increasesmortality in patients with ARDS when compared with a lower tidal volume(6mg/kg predicted body weight), even though it raises PaO2 more in theshorttermthandoesalowertidalvolume.Conservativeuseoffluidsimproveslungfunctionandshortensthedurationofmechanicalventilationandinten-sivecare.2

Improvementsinoxygenation,acid-basestatus,andcardiacoutputareofnomorethantemporarybenefitunlesstheunderlyingdiseaseprocessesarediagnosedandtreatedproperly.Inpatientswithacutelunginjury,sepsismayworseninjurytothelungandotherorgansdespiteoptimalsupportivecare.Similarly,iftheprecipitatingcauseofacuterespiratoryfailureinapatientwithCOPDisnotidentifiedandtreated,supportivecareislikelytobefutile.Com-plicationsmayarisefromthephysiologiceffectsofthegasexchangeabnor-mality,fromthediseaseprocessescausingtheacuterespiratoryfailure,frombeing critically ill and its associated incursions on homeostasis (e.g., sleepdeprivation),orfromiatrogeniccomplicationsoftherapy.

Mechanical Therapy to Improve OxygenationAPaO2greaterthan60mmHg isusuallyadequatetoproduceanSaO2 in

the low to middle 90s.The PaO2 can be increased by the administration ofsupplemental O2, by pharmacologic manipulations, by continuous positiveairwaypressure(CPAP),bymechanicalventilationwithorwithoutmaneuverssuchasPEEP,andbytheproneposition.PEEP,pharmacologicmanipulations,andpositioningareusedprimarilyinpatientswithacutelunginjury(seelater).

The initialchoiceoftheconcentrationandamountofsupplementalO2 isbasedontheseverityofthehypoxemia,theclinicaldiagnosis,thelikelymech-anismcausingthehypoxemia,andtheO2deliverysystemsavailable.ForthetrachealFIO2tobethesameasthedeliveredFIO2,theO2deliverysystemmustdeliveraflowthatmatchesthepatient’speakinspiratoryflowratewithgasofaknownFIO2.High-flowO2blenderscanachievethisgoalbydeliveringgasat80L/minute or greater to a nonintubated patient. These systems require alarge flow of O2 (from a wall unit or tank), however, and are not universallyavailable. Other systems for nonintubated patients (including nasal prongs,simple face masks, and non-rebreather and partial rebreather masks) use a

TREATMENT


SPECIFIC ACUTE RESPIRATORY FAILURE SYNDROMES

Chronic Obstructive Pulmonary DiseaseEPIDEMIOLOGY AND PATHOBIOLOGY

The epidemiology and pathobiology of COPD are discussed in Chapter 88.

CLINICAL MANIFESTATIONSWhen COPD causes acute respiratory failure, patients commonly have a history of increasing dyspnea and sputum production. Acute respiratory failure may manifest in more cryptic ways, however, such as changes in mental status, arrhythmias, or other cardiovascular abnormalities. Acute respiratory failure must be considered whenever patients with COPD have significant nonspecific clinical changes.

DIAGNOSISThe diagnosis can be confirmed or excluded by arterial blood gas analysis. The pH is helpful in assessing whether the hypoventilation is partly or exclu-sively acute: The pH drops by approximately 0.08 for each 10 mm Hg rise in the Paco2 in acute respiratory acidosis without renal compensation. By com-parison, in chronic respiratory acidosis with normal renal compensation, the pH drops only about 0.03 for each 10 mm Hg rise in the Paco2.

simpleregulatorthatmixesroomairwithO2at12L/minutefromawallunitortank,withresultingflowsthatarefrequentlyunabletomatchthepatient’speakinspiratoryflowrate.Thepatiententrainsmoreairfromtheenvironment,and the resulting tracheal FIO2 or partial pressure of oxygen in inspired gas(PIO2)isunknown.Theamountofairentraineddependsonthepatient’sinspi-ratorypatternandminuteventilation.AlthoughtheresultingFIO2isunknown,thesesystemsaresatisfactory if thedelivery isconstantand if theyresult inadequatearterialO2saturation,asmonitoredbyarterialbloodgasesoroxim-etry.NasalprongscandeliveratrachealFIO2ofapproximately0.50,andnon-rebreathermaskscandeliver50to100%O2; inbothcases, thisdependsontheinspiratorypatternandflowrate.Ifonlyhypoventilationor � �V Qmismatchispresent,onlyasmallincrementinFIO2(e.g.,anFIO2of0.24or0.28deliveredby a Venturi principle face mask or by mechanical ventilation; or 1 to 2L/minuteO2deliveredbynasalprongs)islikelytoberequired.Bycomparison,ifmarkedshuntingormanylungunitswithlowbutnotzero � �V Qarethecauseofhypoxemia,aconsiderablyhigherFIO2(e.g.,>0.7)mayberequired,andeventhis high FIO2 may not reverse the hypoxemia. A common practice when asignificant shunt is suspected is to give an FIO2 of 1.0, then adjust the FIO2downwardasguidedbytheresultingPaO2orSaO2.

TheO2concentrationthatistoxictothelungsincriticallyillpatientsisnotknown, but prior injury may provide tolerance to O2 toxicity, whereas otherconditioningagents,suchasbleomycin,mayenhanceoxidativeinjury.AnFIO2of0.7orhigherisgenerallyconsideredinjurioustothenormalhumanlung.Because it is unknown what lower concentration is safe, however, patientsshouldbegiventhelowestFIO2thatprovidesanadequateSaO2(≥90%).IfanFIO2equaltoorgreaterthan0.5to0.7isrequiredforadequateoxygenation,othermeasures,especiallyPEEPorCPAP,shouldbeconsidered.EvenalowerFIO2ofabout0.5maybeassociatedwithimpairedciliaryactionintheairwaysandimpairedbacterialkillingbyalveolarmacrophages,buttheclinicalimpor-tanceoftheseeffectsisnotknown.

A low concentration of supplemental O2 can be administered by nasalprongs or nasal cannula, which most patients find comfortable and allowsthemtocough,speak,eat,anddrinkwhilereceivingO2.Whenthenasalpas-sagesareopen,thePIO2doesnotdependtoomuchonwhetherthepatientbreathes through the nose or the mouth because O2 is entrained from theposteriornasalpharynxduringabreathtakenthroughthemouth.ThelevelofO2 canbeadjustedby the flowrate to thenasalprongs. InpatientswithCOPD,flowsaslowas0.5to2L/minuteareusuallyadequateunlessanintra-pulmonaryshuntiscontributingtothehypoxemia,asusuallyoccursinacutepneumonia. At flows greater than approximately 6L/minute, only a smallfurtheraugmentationinthePIO2canbeachieved.Becausegasflowthroughthenosehasadryingandirritatingeffect,afacemaskshouldbeconsideredathighflowrates.O2facemasksusingtheVenturiprincipleallowtheregula-tionofFIO2andcanbeparticularlyusefulwhenCOPDissuspected,andit isimportanttoavoidtheCO2retentionthatcanbeassociatedwiththeunregu-latedadministrationofO2.AhigherFIO2of0.5tonearly1.0canbeadminis-tered through a non-rebreathing face mask with an O2 reservoir. If an FIO2equaltoorgreaterthan0.70isrequiredformorethanseveralhours,particu-larlyinanunstablepatient,endotrachealintubationshouldbeconsideredsoO2canbeadministeredbyaclosedsystemwithreliablemaintenanceofthepatient’sSaO2.Indicationsforplacinganartificialairwayinapatientwithacuterespiratory failure include airway protection against massive aspiration ofgastric contents, delivery of an increased FIO2, facilitation of prolongedmechanical ventilation, and to aid in the control of respiratory secretions(Chapter105).

Ventilatory maneuvers that may increase arterial oxygenation includemechanical ventilation itself and the administration of PEEP or CPAP, all ofwhichallowventilationofareasofthelungthatwerepreviouslypoorlyven-tilatedorunventilated.Althoughlargetidalvolumeswithmechanicalventila-tion may open areas of atelectasis and may improve oxygenation initially,these higher tidal volumes can cause lung injury, particularly if the lung isalreadyinjured(Chapter105).

CPAPreferstothemaintenanceofpositivepressureduringtherespiratorycyclewhilebreathingspontaneously.PEEPreferstothemaintenanceofposi-tivepressurethroughouttheexpiratorycyclewhenitisappliedtogetherwithmechanicalventilation(Chapter105).CPAPandPEEPcanresultinrecruitmentofmicroatelectaticregionsofthelungthatareperfusedbutwerenotprevi-ouslyventilated,thuscontributingsubstantiallytohypoxemia.CPAPandPEEPhavethetheoreticaladvantageofkeepingsomeoftheseregionsopenduringexhalation,thuspreventingcyclicclosureandreopeningoflungunits,whichcanresultinalveolarwallstressandinjury.

Supportive MeasuresEverypatientwithacuterespiratoryfailureisatriskfordeepveinthrombo-

sis,pulmonarythromboembolism,andgastricstressulceration.Prophylacticanticoagulationisrecommendedinpatientswhoarenotathighriskforbleed-ingcomplications;sequential legcompressiontherapymaybepreferredforhigh-riskpatients(Chapter81).

Thebestmeansofpreventingstressulceration isnotknown,butcurrentevidence indicates that the use of an H2-blocker is superior to the gastricadministrationofsucralfate,basedonalargerandomized,controlledtrialthat

foundahigherincidenceofsignificantbleedinginpatientsreceivingsucral-fate than in those receiving ranitidine. Evidence also indicates that protonpump inhibitors may be useful in the acute care setting.There is little firmevidencetoguidenutritionalmanagementinpatientswithacuterespiratoryfailure(Chapters221and224).

Currentevidencesupportsmaintainingtheheadofthebedata45-degreeangletoreduceaspirationincritically illpatients.Attemptsshouldbemadetoensureanormalday-nightsleeppattern,includingminimizingactivityandreducing direct lighting at night. The patient should change position fre-quently, including sitting in a chair and walking short distances if possible,even while receiving mechanical ventilatory support. Mobilization canenhance the removal of secretions, help maintain musculoskeletal function,reducetheriskofdeepveinthrombosis,andprovidepsychologicalbenefits.

General CareAs soon as acute respiratory failure is confirmed in a patient with COPD,

attention must focus on detecting any precipitating events (Table 104-4),including decreased ventilatory drive, commonly because of oversedation;decreasedmusclestrengthorfunction,oftenrelatedtoelectrolyteabnormali-ties, including hypophosphatemia and hypomagnesemia; decreased chestwallelasticity,possiblyrelatedtoribfracture,pleuraleffusion,ileus,orascites;atelectasis, pneumonia, or pulmonary edema; increased airway resistance,causedbybronchospasmor increasedsecretions;or increasedmetabolicO2requirements, such as with systemic infection. Many of these abnormalitiescanimpairthecoughmechanism,diminishtheclearanceofairwaysecretions,andprecipitateacuterespiratoryfailure.

InfectionThe most common specific precipitating event is airway infection, espe-

cially acute bronchitis. The role played by viral agents, Mycoplasma pneu-moniae, chronic contaminants of the lower airway such as Haemophilus influenzaeandStreptococcus pneumoniae,andotheracutepathogensisdiffi-cult to determine on a clinical or even microbiologic basis. Acute exacerba-tionsofCOPDcommonlyresultfromnewinfectionsratherthanre-emergenceofaninfectionfrompreexistingcolonization.Antibioticsmodestlyshortenthedurationoftheexacerbation,withnosignificantincreaseintoxicity,comparedwithplacebo;theimpactofantibioticsonthesubsequentemergenceofresis-tantorganismsisnotknown.ItisstandardpracticetouseantibioticstotreatapatientwithCOPDwhohasanexacerbationsevereenoughtocauseacuterespiratoryfailureandwhohasevidenceconsistentwithacutetracheobron-chitis(Chapters88and96).Pneumoniamayaccountfor20%ofcasesofacuterespiratoryfailureinpatientswithCOPD.Comparedwiththephysiologicallynormalpopulation,patientswithCOPDwhohavecommunity-acquiredpneu-monia are more likely to have gram-negative enteric bacteria or Legionellainfectionsandaremorelikelytohaveantibiotic-resistantorganisms.

Other Precipitating CausesOther common precipitating causes of acute respiratory failure include

heartfailureandworseningoftheunderlyingCOPD,oftenrelatedtononcom-pliancewithmedications.Lesscommonandoftendifficulttodiagnoseinthissettingispulmonarythromboembolism.

TREATMENT


PROGNOSISAcute respiratory failure in patients with severe COPD is associated with an in-hospital mortality of 6 to 20%. The severity of the underlying disease and the severity of the acute precipitating illness are important determinants of hospital survival. Hospital mortality is higher if the respiratory failure is asso-ciated with a pH less than 7.25. The pH, the Paco2, and other clinical char-acteristics are not very reliable in predicting a particular patient’s chances of survival.

Acute Lung Injury/Acute Respiratory Distress Syndrome

DEFINITIONARDS was first described in 1967 as the abrupt onset of diffuse lung injury characterized by severe hypoxemia (shunting) and generalized pulmonary infiltrates on the chest radiograph in the absence of overt cardiac failure. In the early 1990s the term acute lung injury was officially introduced to include traditional ARDS and less severe forms of lung injury. Both acute lung injury and ARDS, by definition, require bilateral pulmonary infiltrates compatible with pulmonary edema in the absence of clinical heart failure (usually deter-mined by the lack of elevated left atrial pressures). The two are differentiated by the degree of abnormal oxygenation: Patients are defined as having acute lung injury if the Pao2 divided by the Fio2 (Pao2/Fio2, also called the P/F ratio) is less than or equal to 300. When the Pao2/Fio2 is less than or equal to 200, the patient meets the criteria for ARDS.

EPIDEMIOLOGYAcute lung injury and ARDS are major public health problems and major causes of death. The annual incidence of acute lung injury is about 80 cases per 100,000 adult population. Case-fatality rates are 30 to 50% and are highly dependent on disease severity and the underlying predisposing condition.

ETIOLOGYAcute lung injury is a clinical syndrome triggered by some other cause (Table 104-5). This underlying precipitating factor may affect and injure the lungs directly, such as in diffuse pneumonia or aspiration of gastric contents, or it may affect the lungs indirectly, such as in severe sepsis (Chapter 108) or severe nonthoracic trauma (Chapter 112). Severe sepsis is the most common pre-cipitating cause of acute lung injury worldwide. The organisms vary widely, ranging from gram-negative and gram-positive bacteria and viruses (e.g., H1N1 influenza in 2009) to leptospiral infections or malaria. It may be dif-ficult to determine whether pneumonia is diffuse, with endobronchial spread involving most of the lungs, or whether localized pneumonia has precipitated a sepsis syndrome, with secondary injury to other parts of the lung.

Site of CareManypatientswithCOPDandacuterespiratoryfailurecanbemanagedon

a general medical hospital floor rather than in an intensive care unit if theprecipitating cause of acute respiratory failure has been diagnosed and ispotentiallyresponsivetoappropriatetherapy,ifanybloodgasabnormalitiesrespondtoO2therapyandarenotlife-threatening,ifthepatientcancooperatewith the treatment, and if appropriate nursing and respiratory care can beprovided (Chapter 88). An unstable patient who requires closer observationandmonitoringshouldbeadmittedtoanintensivecareunit.

Mechanical TherapyThedecisiontousemechanicalventilationinpatientswithCOPDandacute

respiratoryfailuremustbemadeonclinicalgroundsandisnotdictatedbyanyparticulararterialbloodgasvalues.Ingeneral,ifthepatientisalertandisabletocooperatewith treatment,mechanicalventilation isunlikely tobeneces-sary. Ifventilatorysupportisrequired(Chapter105),thedecisioniswhetherto use noninvasive positive-pressure ventilation therapy (without endotra-cheal intubation) or endotracheal intubation with positive-pressure ventila-tion. Many studies have demonstrated that noninvasive positive-pressureventilationispreferredforpatientswithCOPDandcandecreasemortality ifapplied in appropriate patients with no factors that are likely to lead tocomplications.3

TABLE 104-4 KEYPRINCIPLESINTHEMANAGEMENTOFCHRONICOBSTRUCTIVEPULMONARYDISEASEPATIENTSWITHACUTERESPIRATORYFAILURE

1. Monitor and treat life-threatening hypoxemia (these measures should be performed virtually simultaneously).a. Assess the patient clinically, and measure oxygenation by arterial blood gases

and/or oximetry.(1) If the patient is hypoxemic, initiate supplemental oxygen therapy with

nasal prongs (low flows [0.5-2. L/min] are usually sufficient) or by Venturi face mask (24 or 28% oxygen delivered).

(2) If the patient needs ventilatory support, consider noninvasive ventilation.(3) Determine whether the patient needs to be intubated; this is almost

always a clinical decision. Immediate action is required if the patient is comatose or severely obtunded.

b. A reasonable goal in most patients is PaO2 of 55-60 mm Hg or SaO2 of 88-90%.c. After changes in FIO2, check blood gases and check regularly for signs of

carbon dioxide retention.2. Start to correct life-threatening acidosis.

a. The most effective approach is to correct the underlying cause of ARF (e.g., bronchospasm, infection, heart failure).

b. Consider ventilatory support, based largely on clinical considerations.c. With severe acidosis, the use of bicarbonate can be considered, but it is often

ineffective, and there is little evidence of a clinical benefit.3. If ventilatory support is required, consider noninvasive mechanical ventilation.

a. The patient must have intact upper airway reflexes and be alert, cooperative, and hemodynamically stable.

b. Careful monitoring is required; if the patient does not tolerate the mask, becomes hemodynamically unstable, or has a deteriorating mental status, consider intubation.

4. Treat airway obstruction and the underlying disease process that triggered the episode of ARF.a. Treat airway obstruction with pharmacologic agents: systemic corticosteroids

and bronchodilators (ipratropium and/or β-adrenergic agents).b. Improve secretion clearance: encourage the patient to cough, administer chest

physical therapy if cough is impaired and a trial appears effective.c. Treat the underlying disease process (e.g., antibiotics, diuretics).

5. Prevent complications of the disease process and minimize iatrogenic complications.a. Pulmonary thromboembolism prophylaxis: use subcutaneous heparin if no

contraindications exist.b. Gastrointestinal complications: administer prophylaxis for gastrointestinal

bleeding.c. Hemodynamics: if the patient is ventilated, monitor and minimize auto-PEEP.

(1) Treat the underlying obstruction.(2) Minimize minute ventilation; use controlled hypoventilation.(3) Use small tidal volumes; increase the inspiratory flow rate to decrease the

inspiratory time and lengthen the expiratory time.d. Cardiac arrhythmias: maintain oxygenation and normalize electrolytes.

ARF = acute respiratory failure; Fio2 = fraction of inspired oxygen; Pao2 = partial pressure of oxygen in arterial blood; PEEP = positive end-expiratory pressure; Sao2 = oxygen saturation.

TABLE 104-5 DISORDERSASSOCIATEDWITHACUTELUNGINJURYANDACUTERESPIRATORYDISTRESSSYNDROME

COMMONSepsis (gram-positive or gram-negative bacterial, viral, fungal, or parasitic infection)Diffuse pneumonia (bacterial, viral, or fungal)Aspiration of gastric contentsTrauma (usually severe)

LESS COMMONNear-drowning (fresh or salt water)Drug overdose

Acetylsalicylic acidHeroin and other narcotic drugs

Massive blood transfusion (likely a marker of severe trauma, but also seen with severe gastrointestinal bleeding, especially in patients with severe liver disease)

Leukoagglutination reactionsInhalation of smoke or corrosive gases (usually requires high concentrations)PancreatitisFat embolism

UNCOMMONMiliary tuberculosisParaquat poisoningCentral nervous system injury or anoxia (neurogenic pulmonary edema)Cardiopulmonary bypass


PATHOBIOLOGYPathologyDespite the variety of underlying disease processes leading to acute lung injury, the response to these insults in the lung is monotonously characteris-tic, with similar clinical findings, physiologic changes, and morphologic abnormalities. The pathologic abnormalities in acute lung injury and ARDS are nonspecific and are described as diffuse alveolar damage by pathologists. The initial process is inflammatory, with neutrophils usually predominating in the alveolar fluid. Hyaline membranes develop, similar to those seen in premature infants with infant respiratory distress syndrome, presumably related to the presence of large-molecular-weight proteins that have leaked into the alveolar space. Alveolar flooding leads to impairment of surfactant, which is abnormal in quantity and quality. The result is microatelectasis, which may be associated with impaired immune function. Cytokines and other inflammatory mediators are usually markedly elevated, although with different patterns over time in the bronchoalveolar lavage fluid and the sys-temic blood. Lung repair is also disturbed; early evidence of pro-fibrotic processes includes the appearance of breakdown products of pro-collagen in the bronchoalveolar lavage fluid, followed by scarring. The pulmonary fibro-sis observed on lung biopsy or at autopsy is identical to that seen in patients with idiopathic pulmonary fibrosis (Chapter 92). Because lung function improves over time in survivors of ARDS, however, it has been assumed that this scarring is often reversible.

PathophysiologyThe physiologic abnormalities are dominated by severe hypoxemia with shunting, decreased lung compliance, decreased functional residual capacity, and increased work of breathing. Initially, the Paco2 is low or normal, usually associated with increased alveolar ventilation. The initial abnormalities in oxygenation are thought to be related to alveolar flooding and collapse. As the disease progresses, especially in patients who require ventilatory support, fibroproliferation develops; the lungs (including alveoli, blood vessels, and small airways) remodel and scar, with a loss of microvasculature. These changes may lead to pulmonary hypertension and increased dead space; marked elevations in minute ventilation are required to achieve a normal Paco2, even as oxygenation abnormalities are improving.

CLINICAL MANIFESTATIONSIn most cases of acute lung injury, the onset either coincides with or occurs within 72 hours of the onset of the underlying disease process; the mean time from onset of the underlying cause to onset of acute lung injury is 12 to 24 hours. The presenting picture is dominated by respiratory distress and the accompanying laboratory findings of severe hypoxemia and generalized infil-trates or opacities on the chest radiograph. Alternatively, it may be dominated by manifestations of the underlying disease process, such as severe sepsis with hypotension and other manifestations of systemic infection.

DIAGNOSISThe key to diagnosis is to distinguish ARDS from cardiogenic pulmonary edema (Table 104-6). No specific biochemical test exists to define ARDS. Certain blood or bronchoalveolar lavage (Chapter 85) abnormalities are fre-quent but are not sufficiently specific to be useful clinically.

TreatmentforacutelunginjuryandARDSconsistspredominantlyofrespi-ratorysupportandtreatmentoftheunderlyingdisease(Fig.104-4).Althoughsepsisisacommonpredisposingconditionforthedevelopmentofacutelunginjury,asmallstudyexaminingtheusefulnessofactivatedproteinCinpatientswithacutelunginjurydidnotdemonstrateanybeneficialeffectsintermsofventilator-freedaysormortality.

Mechanical TherapyCurrentrecommendationsformechanicalventilationviaendotrachealintu-

bation (Table 104-7) emphasize lower tidal volumes based on the patient’spredictedbodyweight(Chapter105).4PEEPisamainstayintheventilatorystrategy for acute lung injury; although the method for determining theoptimallevelofPEEPhasnotbeenestablished,higherPEEPlevelsappeartobenefitpatientswithARDS.4,5PEEPmayallowa lowerFIO2toprovideade-quate oxygenation, thus avoiding O2 toxicity. It also may prevent the cycliccollapseandreopeningoflungunits,aprocessthatisthoughttobeamajor

TREATMENT

cause of ventilator-induced lung injury, even when adequate oxygenationcanbeobtainedatrelativelylowlevelsofFIO2.Theearlyuseofcisatracuriumbesylate(15mgrapidinfusionfollowedby37.5mg/hrfor48hours),aneuro-muscularblocker,canreduceARDSmortalityratesbyabout25%.6InpatientswithsevereARDSwhodonotrespondtostandardtherapybutotherwisehavea reasonable life expectancy, extracorporeal membrane oxygenation canimprovethe6-monthsurvivalfrom47to63%atanacceptablecostofabout$35,000perquality-adjustedyearoflifesaved.7

Acute Respiratory Failure without Lung DiseaseAcute respiratory failure without pulmonary abnormalities (see Table 104-2) is seen in patients with depressed ventilatory drive secondary to central nervous system dysfunction and in patients with severe neuromuscular disease. The prototypical patient with suppressed ventilatory drive has taken an overdose of a sedative or tranquilizing medication (Chapter 110). The prototypical patient with neuromuscular disease has Guillain-Barré syn-drome (Chapter 428). The treatment for both types of patients is supportive. In the case of a patient with a sedative overdose, the threshold for intubation with mechanical ventilatory support should be low because this temporary condition is quickly reversible when the responsible drug is eliminated. Such a patient may require intubation for airway protection against aspiration of gastric contents.

Patients with Guillain-Barré syndrome or other forms of progressive neu-romuscular disease should be monitored with serial measurements of vital capacity. In general, when the vital capacity decreases to less than 10 to 15 mL/kg body weight, intubation and mechanical ventilatory support should be considered without regard to the patient’s Paco2.

TABLE 104-6 FEATURESASSOCIATEDWITHNONCARDIOGENICANDCARDIOGENICPULMONARYEDEMA*

NONCARDIOGENIC EDEMA (ARDS)CARDIOGENIC EDEMA/VOLUME

OVERLOADPRIOR HISTORYYounger OlderNo history of heart disease Prior history of heart diseaseAppropriate fluid balance (difficult to

assess after resuscitation from shock or trauma)

Hypertension, chest pain, new-onset palpitations; positive fluid balance

PHYSICAL EXAMINATIONFlat neck veins Elevated neck veinsHyperdynamic pulses Left ventricular enlargement, lift, heave,

dyskinesisPhysiologic gallop S3 and S4; murmursAbsence of edema Edema: flank, presacral, legs

ELECTROCARDIOGRAMSinus tachycardia, nonspecific ST-T wave

changesEvidence of prior or ongoing ischemia,

supraventricular tachycardia, left ventricular hypertrophy

CHEST RADIOGRAPHNormal heart size CardiomegalyPeripheral distribution of infiltrates Central or basilar infiltrates;

peribronchial and vascular congestionAir bronchograms common (80%) Septal lines (Kerley’s lines), air

bronchograms (25%), pleural effusion

HEMODYNAMIC MEASUREMENTSPulmonary artery wedge pressure

<15 mm Hg, cardiac index >3.5 L/min/m2

Pulmonary capillary wedge pressure >18 mm Hg, cardiac index <3.5 L/min/m2 with ischemia, may be >3.5 L/min/m2 with volume overload

*These features are neither highly sensitive nor specific. Although the findings are more commonly associated with the type of pulmonary edema as listed, they do not have high positive or negative predictive value.ARDS = acute respiratory distress syndrome.


FIO2£0.6

Acute Lung Injury/Acute Respiratory Distress Syndrome

Place on non-rebreathing mask with 100% O2

Attach pulse oximeter for SaO2 and measure ABG

Begin management of precipitating events or associated underlying diseases and MSOF

Consider right heart catheterization if hypotension present and diagnosis uncertain

Patient alert and hemodynamically stable: RR<35, PaCO2<35 mm Hg; SaO2>88%

Adjust FIO2 to yield SaO2 88-95%Consider NIPPV to relieve dyspnea

Intubate: volume cycled ventilation: VT 6 mL/kg PBW; FIO2 1.0; PEEP 5 cm H2O assist control mode; conscious sedation and maintain comfort

Code status discussed; NPO; H2 blocker; DVT prophylaxis; semi-recumbent (45°) position

Continue to increase PEEP by 3-5 cm H2O increments; repeat above assessment until SaO2>88% and FIO2<0.6

Decrease VT by 1 mL/kg PBW decrements (to minimum of 4) until Pplat<30 cm H2O; allow PaCO2 to rise slowly

Consider other modes of ventilatory supportNote: If chest wall compliance is markedly

decreased (e.g., massive ascites), then it may not be necessary to decrease VT

Decrease FIO2 by 0.1 decrements to 0.4 and/or decrease PEEP by 3-5 cm H2O to 8 cm H2O (or consider ARDSNet PEEP/FIO2 ladder)

Wean from ventilator as tolerated

Maintain ventilator settingsContinue pulse oximetry;

repeat ABG in 4-8 h or as clinically indicated

Increase PEEP by 3-5 cm H2O increments to maximum of 25 cm H2O and/or increase FIO2 by 0.1 increments to 1.0

Consider prone position; increase sedation and/or paralysis

Accept PaCO2 rise; accept pH decrease to 7.15 or lower; accept SaO2 ≈ 85%

Increase PEEP in 3-5 cm H2O increments (or consider ARDSNet PEEP/FIO2 ladder)

Monitor ABG, blood pressure, urine output, capillary refill time, and (if available)

cardiac index

SaO2>95%

SaO2>95% orPaO2>80 mm Hg

SaO2<88% orPaO2<55 mm Hg

SaO2 remains<88%PaO2 remains<55 mm Hg

SaO2 88-95% orPaO2 55-80 mm Hg

SaO2<88%

Inadequate perfusion Adequate perfusion

Measure plateaupressure

Repeat ABG

Repeat assessment of plateau pressure and ABG

Give volume

FIO2<0.6

£30 cm H2O >30 cm H2O

Maintain urine output@fluid intake 24-48 h

Reduce FIO2 untilSaO2<96%

Yes No

Consider right heart catheterization

FIGURE 104-4. Algorithm for the initial management of acute respiratory distress syndrome.ABG=arterialbloodgasanalysis;CO2=carbondioxide;DVT=deepveinthrombosis;FIO2= inspired oxygen concentration; MSOF= multisystem organ failure; NIPPV= noninvasive intermittent positive-pressure ventilation; O2= oxygen; PaCO2= arterial partial pressureof carbon dioxide; PaO2 = arterial partial pressure of oxygen; PBW = predicted body weight; PEEP = positive end-expiratory pressure; Pplat = plateau pressure; RR = respiratory rate;SaO2=arterialoxygensaturation;VT=tidalvolume.

TABLE 104-7 ARDSNetVENTILATORYMANAGEMENTPROTOCOLFORTIDALVOLUMEANDPLATEAUPRESSURE

Calculate PBW:Male PBW: 50 + 2.3 (height in inches − 60) or 50 + 0.91 (height in centimeters

− 152.4)Female PBW: 45.5 + 2.3 (height in inches − 60) or 45.5 + 0.91 (height in

centimeters − 152.4)Select assist control modeSet initial VT at 8 mL/kg PBWReduce VT by 1 mL/kg at intervals < 2 hr until VT = 6 mL/kg PBWSet initial RR to approximate baseline minute ventilation (maximum RR = 35/min)Set inspiratory flow rate higher than patient’s demand (usually > 80 L/min)Adjust VT and RR further to achieve Pplat and pH goals

If Pplat > 30 cm H2O: decrease VT by 1 mL/kg PBW (minimum = 4 mL/kg PBW)If pH ≤ 7.30, increase RR (maximum = 35)If pH < 7.15, increase RR to 35; consider sodium bicarbonate administration or

increase VT

PBW = predicted body weight; Pplat = plateau pressure (airway pressure at the end of delivery of a tidal volume breath during a condition of no airflow); RR = respiratory rate; Vt = tidal volume.See the ARDSNet website (http://www.ardsnet.org) for further details about the protocol, including the approach for setting positive end-expiratory pressure and fraction of inspired oxygen.

1. Wheeler AP, Bernard GR, Thompson BT, et al. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network: pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med. 2006;354:2213-2224.

2. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clini-cal Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575.

3. Ram FS, Lightowler JV, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2004.3.CD004104.

4. Putensen C, Theuerkauf N, Zinserling J, et al. Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury. Ann Intern Med. 2009;151:566-576.

5. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303:865-873.

6. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107-1116.

7. Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventila-tor support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomized controlled trial. Lancet. 2009;374:1351-1363.

SUGGESTED READINGS

Del Sorbo L, Slutsky AS. Acute respiratory distress syndrome and multiple organ failure. Curr Opin Crit Care. 2011;17:1-6. Review.

Esan A, Hess DR, Raoof S, et al. Severe hypoxemic respiratory failure: part 1—ventilatory strategies. Chest. 2010;137:1203-1216. Review.

Raoof S, Goulet K, Esan A, et al. Severe hypoxemic respiratory failure: part 2—nonventilatory strategies. Chest. 2010;137:1437-1448. Review.

http://www.ardsnet.org

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