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

TABLE 104-1 ABBREVIATIONS COMMONLY USED IN ACUTE

RESPIRATORY FUNCTION
ABG Arterial blood gas or arterial blood gas analysis
ALI Acute lung injury
ARDS Acute respiratory distress syndrome
ARF Acute respiratory failure
cm H2O Centimeters of water
CaO2 Content of oxygen in arterial blood
CCO2 Content of oxygen in end-capillary blood
CO2 Carbon dioxide
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure (used when positive pressure
during exhalation is applied with spontaneous ventilation)
CvO2 Content of oxygen in mixed venous blood
FIO2 Fraction of inspired oxygen
g/dL Grams per deciliter
HbO2 Saturation of hemoglobin by oxygen
L/min Liters per minute
mL/kg Milliliters per kilogram
mL/min Milliliters per minute
mm Hg Millimeters of mercury
NIPPV Noninvasive positive-pressure ventilation
O2 Oxygen
P(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 gas
PaCO2 Partial pressure of carbon dioxide in arterial blood
PAO2 Partial pressure of oxygen in alveolar gas
PaO2 Partial pressure of oxygen in arterial blood
PaO2/FIO2 Ratio of partial pressure of oxygen in arterial blood to fraction of
inspired oxygen
PBW Predicted body weight
PcCO2 Partial pressure of carbon dioxide in end-capillary blood
PcO2 Partial pressure of oxygen in end-capillary blood

104 
PEEP Positive end-expiratory pressure (used when positive pressure during
exhalation is applied with mechanical ventilation)
P/F PaO2/FIO2 ratio

ACUTE RESPIRATORY FAILURE PIO2

PO2
Partial pressure of oxygen in inspired gas
Partial pressure of oxygen
LEONARD D. HUDSON AND ARTHUR S. SLUTSKY PvCO2 Partial pressure of carbon dioxide in mixed venous blood
PvO2 Partial pressure of oxygen in mixed venous blood
Q Blood flow or perfusion
RR Respiratory rate
ACUTE RESPIRATORY FAILURE
SaO2 Percentage of saturation of hemoglobin by oxygen in arterial blood
DEFINITION V Ventilation
Acute respiratory failure occurs when dysfunction of the respiratory system V Q Ventilation-to-perfusion ratio
results in abnormal gas exchange that is potentially life-threatening. Each
element of this definition is important to understand. The term acute implies VT Tidal volume
630 CHAPTER 104  ACUTE RESPIRATORY FAILURE
 

TABLE 104-2 SYSTEMS TO CLASSIFY ACUTE RESPIRATORY FAILURE

HYPOXIC VERSUS HYPERCAPNIC-HYPOXIC ARF ARF WITH AND WITHOUT CHRONIC LUNG DISEASE
Causes of Hypoxic ARF With Chronic Lung Disease
Acute lung injury/ARDS COPD
Pneumonia Asthma
Pulmonary thromboembolism Parenchymal lung diseases
Acute lobar atelectasis Restrictive lung/chest wall diseases
Cardiogenic pulmonary edema
Without Chronic Lung Disease‡
Lung contusion
Acute collagen vascular disease (Goodpasture’s syndrome, systemic lupus Acute lung injury/ARDS
erythematosus) Pneumonia
Pulmonary thromboembolism
Causes of Hypercapnic-Hypoxic ARF
ARF BY ORGAN SYSTEM INVOLVED
Pulmonary disease
COPD Respiratory (Lungs and Thorax)
Asthma: advanced, acute, severe asthma Airway/airflow obstruction
Drugs causing respiratory depression COPD
Neuromuscular Asthma
Guillain-Barré syndrome Pulmonary parenchyma
Acute myasthenia gravis Pneumonia
Spinal cord tumors Acute lung injury/ARDS
Metabolic derangements causing weakness (including hypophosphatemia, Acute flare of chronic collagen vascular disease (e.g., Goodpasture’s syndrome,
hypomagnesemia) systemic lupus erythematosus)
Musculoskeletal
Kyphoscoliosis Central Nervous System
Ankylosing spondylitis Respiratory depression
Obesity hypoventilation syndrome (often with additional acute, superimposed Increased sedatives, tranquilizers with respiratory effect; opiates; alcohol
abnormality as cause of ARF) Brain stem and spinal cord involvement
ETIOLOGIC MECHANISMS OF HYPOXEMIA Tumors, trauma, vascular accidents
Normal P(A-a)O2* Neuromuscular
↓PIO2 Guillain-Barré syndrome
High altitude; inadvertent administration of low FIO2 gas mixture Myasthenia gravis
Hypoventilation Cardiovascular
See causes of hypercapnic-hypoxic ARF above
Cardiogenic pulmonary edema
Increased P(A-a)O2* Pulmonary thromboembolism
Ventilation-perfusion ( V Q ) mismatch Renal/Endocrine
Airway disease
Volume overload
Vascular disease, including pulmonary thromboembolism
Metabolic abnormalities
Shunt
Acute lung injury/ARDS
Pneumonia
Parenchymal lung disease
Cardiogenic pulmonary edema
Pulmonary infarction
Diffusion limitation†
*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.

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.
PATHOBIOLOGY
Abnormal 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
 CHAPTER 104  ACUTE RESPIRATORY FAILURE
CaO2
SaO2
100 Dissolved
20
80
15
CaO2 (mL/dL)
SaO2 (%)
60
Normal arterial
Mixed venous
10
40
5 0.28 by face mask or 1 to 2 L/minute O2 by nasal prongs, in patients with
20
0 0
0 20 40 60 80 100 600
PaO2 (mm Hg)
FIGURE 104-1.  Oxyhemoglobin association-dissociation curve. The axis for oxygen
saturation in the arterial blood (SaO2) is on the left, and the axis for arterial content of oxygen
(CaO2) is on the right. CaO2 is the sum of the oxygen dissolved in plasma (denoted as “Dis-
solved” in the figure) plus the oxygen bound to hemoglobin. At a normal hemoglobin, most
of the oxygen is carried in combination with hemoglobin, with only a relatively small
amount of oxygen dissolved in plasma. When the value of the arterial partial pressure of
oxygen (PaO2) is on the “flat” portion of the curve (PaO2 ≥60 to 65 mm Hg, normal partial
pressure of carbon dioxide [PCO2], and normal pH), raising the PaO2 further has relatively
little effect on total oxygen content. Increases in temperature, PCO2, hydrogen ion concen-
tration, or 2,3-diphosphoglycerate cause a rightward shift in the oxyhemoglobin associa-
tion-dissociation curve.
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.
Pathophysiology
Five 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 quickly, even if data are limited. The clinician must obtain updated informa-
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
631
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
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 MANIFESTATIONS
The 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).
DIAGNOSIS
As 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
tion continually and should view most therapeutic decisions as therapeutic
trials, with careful monitoring to assess desired benefits and possible detri-
mental effects.
Clinical Evaluation
The 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
632 CHAPTER 104  ACUTE RESPIRATORY FAILURE
 

• •
Valv=6.1 Valv=5.6

PaO2=41 PaO2=117 PaO2=105

PaCO 2=46 PaCO 2=32 PaCO 2=37

Cv O 2=11.9 Cv O 2=11.9
Pv O 2=32 Pv O 2=31
Pv CO 2=46 Pv CO 2=46
FIGURE 104-2.  Arterial oxygenation. Comparison of the
C cO 2=14.8 C cO 2=20.1 C cO 2=11.9 C cO 2=19.9 effect on arterial oxygenation of increasing the fraction of
P cO 2=41 P cO 2=117 P cO 2=32 P cO 2=105 inspired oxygen (FIO2) from breathing ambient air (FIO2 = 0.21) (A)
P cCO 2=46 P cCO 2=32 P cCO 2=46 P cCO 2=37 and breathing 100% oxygen (FIO2 = 1.0) (B) with a low ventilation-
 (left) and a shunt (right), using a two-
to-perfusion ratio ( V Q)
compartment lung model. Shunting and decreased V Q  can lead
Ca O 2=16.9 Ca O 2=16.9 to identical arterial blood gases (partial pressure of oxygen in
Pa O 2=50 PaO2=50 arterial blood [PaO2] = 50 mm Hg; partial pressure of carbon
FI O2=0.21 PaCO 2=40 PaCO 2=40 dioxide in arterial blood [PaCO2] = 40 mm Hg). The response to
supplemental oxygen administration is markedly different.
A Hypoxemia is only partially corrected by breathing 100% oxygen
• •
Valv=5.8 when a shunt is present because arterial oxygenation represents
Valv=6.3
an average of the end-capillary oxygen content (CCO2) from
PaO2=665 PaO2=682 PaO2=677 various parts of the lung, not an average of the partial pressures
of oxygen (partial pressure of carbon dioxide in the end-capillary
PaCO 2=48 PaCO 2=31 PaCO 2=36
blood [PcCO2]). When the CCO2 values are mixed, the PaO2 is deter-
mined from the resultant content of oxygen in the arterial blood
(CaO2) by the oxyhemoglobin association-dissociation relation-
 (as is often the case in patients
ship (see Fig. 104-1). With low V Q
Cv O 2=17.0 Cv O 2=14.1 with chronic obstructive pulmonary disease), an increase in FIO2
Pv O 2=53 Pv O 2=38 increases the alveolar partial pressure of oxygen (PO2) of the low
Pv CO 2=48 Pv CO 2=46 V Q unit and leads to a marked increase in arterial PO . The values
2
in this figure were generated from modeling to result in the same
C cO 2=22 C cO 2=22 C cO 2=14.1 C cO 2=22 PaCO2 (40 mm Hg) for all four situations shown; this is the reason
 alv) for some of the
for slight changes in alveolar ventilation ( V Q
P cO 2=665 P cO 2=682 P cO 2=38 P cO 2=667
conditions. Several assumptions are made: (1) no diffusion limita-
P cCO 2=48 P cCO 2=31 P cCO 2=46 P cCO 2=36
tion is present; (2) oxygen consumption = 300 mL/minute, and
CO2 production = 240 mL/minute; (3) cardiac output = 6.0 L/
Ca O 2=22 Ca O 2=19.1 minute; (4) the low V Q  regions in the left panels represent 60%
of the cardiac output perfusing alveoli with a V Q  25% of normal;
PaO2=672 PaO2=76
PaCO 2=40 PaCO 2=40 and (5) the shunts in the right panels represent a 37% shunt
FI O2=1.0
(i.e., 37% of the cardiac output is perfusing alveoli with no
B ventilation).

Physical findings may be associated with a particular pathologic lung

TABLE 104-3 CLINICAL MANIFESTATIONS OF HYPOXEMIA process, such as pneumonia, causing bronchial breathing and crackles on
AND HYPERCAPNIA auscultation, or the crackles (rales) of cardiogenic pulmonary edema
HYPOXEMIA HYPERCAPNIA
(Chapter 58). Abnormal findings may be minimal or absent in patients with
acute lung injury or pulmonary thromboembolism.
Tachycardia Somnolence In some patients, the clinical picture is dominated by the underlying
Tachypnea Lethargy disease process, particularly with diseases that cause acute lung injury, such
Anxiety Restlessness as sepsis (Chapter 108), severe pneumonia (Chapter 97), aspiration of
Diaphoresis Tremor gastric contents (Chapter 94), and trauma. In these conditions the physical
examination is often nonspecific, with no obvious clues except, for example,
Altered mental status Slurred speech
fever with sepsis or pneumonia and hypotension with septic shock.
Confusion Headache
Cyanosis Asterixis Assessment of Physiologic Abnormalities
Hypertension Papilledema The clinical suspicion of acute respiratory failure must be addressed by arte-
Hypotension Coma
rial blood gas analysis to answer several questions.
1. Is hypoxemia present? The answer is based largely on the value of the Pao2
Bradycardia Diaphoresis or Sao2, and the degree of the hypoxemia not only confirms the diagnosis
Seizures of acute respiratory failure but also helps define its severity.
Coma 2. Is hypoventilation present? If the Paco2 is elevated, alveolar hypoventilation
Lactic acidosis* is present.
*Usually requires additional reduction in oxygen delivery because of inadequate cardiac output,
3. Does the degree of hypoventilation explain the hypoxemia? If the P(A-a)o2 is
severe anemia, or redistribution of blood flow. 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-
findings. Cyanosis, which requires at least 5 g/dL of unsaturated hemoglobin emia, another condition must be present; common diagnoses include
to be detectable, may not be seen before serious tissue hypoxia develops, COPD, severe asthma, and early-stage acute respiratory distress syndrome
especially in patients with underlying anemia. (ARDS).
Pulmonary symptoms and signs often reflect the respiratory disease 4. If hypoxemia exists without hypoventilation, an elevated P(A-a)o2 should
causing the acute respiratory failure. Examples include cough and sputum be confirmed, and the response to breathing an enhanced O2 mixture
with pneumonia (Chapter 97) or chest pain from pulmonary thromboem- would answer this question: Is the increase in P(A-a)o2 the result of a
bolism with infarction (Chapter 98). Dyspnea and respiratory distress are V Q abnormality or of shunting? If hypoxemia is primarily the result
nonspecific reflections of the respiratory system’s difficulty in meeting the of a V Q abnormality, the likely cause is an airway disease, either
increased demands from pulmonary and nonpulmonary diseases. COPD or acute severe asthma, or a vascular disease, such as pulmonary
 CHAPTER 104  ACUTE RESPIRATORY FAILURE
 
633
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
A studies can detect diabetic ketoacidosis or renal failure as contributing causes.

B reduce the acute threat to life, (2) improvement of the acidosis if it is consid-
C disease process is not clear. Although normalization of the arterial pH was
FIGURE 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 neuromuscular
disease as the cause of acute respiratory failure. B, Localized alveolar filling opacity, most
commonly seen with acute pneumonia. C, Diffuse bilateral alveolar filling opacities
consistent with acute lung injury and acute respiratory distress syndrome. The CT scan in cations by improving the level of acidosis; it usually is not necessary to normal-
C shows a small left pneumothorax and cavities or cysts that are not apparent on the
anteroposterior chest radiograph.
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 Radiography
The 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 Evaluations
All 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.
TREATMENT
General Measures
The management of acute respiratory failure depends on its cause, its clini-
cal manifestations, and the patient’s underlying status. Certain goals apply to
all patients: (1) improvement of the hypoxemia to eliminate or markedly
ered life-threatening, (3) maintenance of cardiac output or improvement if
cardiac output is compromised, (4) treatment of the underlying disease
process, and (5) avoidance of predictable complications.
The precise methods for improving hypoxemia depend on the cause of the
acute respiratory failure. An increase in the inspired O2 concentration is a
cornerstone of treatment for nearly all patients, however.
The level of acidosis that requires treatment other than for the underlying
suggested in the past, respiratory acidosis is apparently well tolerated in many
patients with severe ARDS, so a patient with a pH of 7.15 or greater may not
require bicarbonate therapy. If the acidemia coexists with clinical complica-
tions, such as cardiac arrhythmias or a decreased level of consciousness, that
have no other obvious cause, treatments to increase pH should be considered.
The therapeutic goal is alleviation or reduction of the accompanying compli-
ize the pH (Chapter 120).
The maintenance of cardiac output is crucial for O2 delivery in acute respira-
tory failure, especially because mechanical ventilation and positive end-expi-
ratory pressure (PEEP) may compromise cardiac output. Placement of a
pulmonary artery catheter allows measurement of cardiac output and filling
pressures, but patients who have these catheters do no better than similar
patients managed without them. 1 
Many therapeutic interventions that improve short-term physiologic vari-
ables may worsen long-term, clinically important outcomes. Transfusing all
patients to maintain a hemoglobin greater than 10 g/dL increases mortality in
critically ill patients who have not had an acute myocardial infarction and do
not have unstable angina, even though the O2 carrying capacity of the blood
is acutely increased. Use of a relatively large tidal volume (e.g., 12 mL/kg pre-
dicted body weight, which is equivalent to approximately 10 to 10.5 mL/kg
measured body weight in patients who are somewhat overweight) increases
mortality in patients with ARDS when compared with a lower tidal volume
(6 mg/kg predicted body weight), even though it raises PaO2 more in the
short term than does a lower tidal volume. Conservative use of fluids improves
lung function and shortens the duration of mechanical ventilation and inten-
sive care. 2 
Improvements in oxygenation, acid-base status, and cardiac output are of
no more than temporary benefit unless the underlying disease processes are
diagnosed and treated properly. In patients with acute lung injury, sepsis may
worsen injury to the lung and other organs despite optimal supportive care.
Similarly, if the precipitating cause of acute respiratory failure in a patient with
COPD is not identified and treated, supportive care is likely to be futile. Com-
plications may arise from the physiologic effects of the gas exchange abnor-
mality, from the disease processes causing the acute respiratory failure, from
being critically ill and its associated incursions on homeostasis (e.g., sleep
deprivation), or from iatrogenic complications of therapy.
Mechanical Therapy to Improve Oxygenation
A PaO2 greater than 60 mm Hg is usually adequate to produce an SaO2 in
the low to middle 90s. The PaO2 can be increased by the administration of
supplemental O2, by pharmacologic manipulations, by continuous positive
airway pressure (CPAP), by mechanical ventilation with or without maneuvers
such as PEEP, and by the prone position. PEEP, pharmacologic manipulations,
and positioning are used primarily in patients with acute lung injury (see later).
The initial choice of the concentration and amount of supplemental O2 is
based on the severity of the hypoxemia, the clinical diagnosis, the likely mech-
anism causing the hypoxemia, and the O2 delivery systems available. For the
tracheal FIO2 to be the same as the delivered FIO2, the O2 delivery system must
deliver a flow that matches the patient’s peak inspiratory flow rate with gas of
a known FIO2. High-flow O2 blenders can achieve this goal by delivering gas at
80 L/minute or greater to a nonintubated patient. These systems require a
large flow of O2 (from a wall unit or tank), however, and are not universally
available. Other systems for nonintubated patients (including nasal prongs,
simple face masks, and non-rebreather and partial rebreather masks) use a
634 CHAPTER 104  ACUTE RESPIRATORY FAILURE
simple regulator that mixes room air with O2 at 12 L/minute from a wall unit
or tank, with resulting flows that are frequently unable to match the patient’s
peak inspiratory flow rate. The patient entrains more air from the environment,
and the resulting tracheal FIO2 or partial pressure of oxygen in inspired gas
(PIO2) is unknown. The amount of air entrained depends on the patient’s inspi-
ratory pattern and minute ventilation. Although the resulting FIO2 is unknown,
these systems are satisfactory if the delivery is constant and if they result in
adequate arterial O2 saturation, as monitored by arterial blood gases or oxim-
etry. Nasal prongs can deliver a tracheal FIO2 of approximately 0.50, and non-
rebreather masks can deliver 50 to 100% O2; in both cases, this depends on
the inspiratory pattern and flow rate. If only hypoventilation or V Q  mismatch
is present, only a small increment in FIO2 (e.g., an FIO2 of 0.24 or 0.28 delivered
by a Venturi principle face mask or by mechanical ventilation; or 1 to 2 L/
minute O2 delivered by nasal prongs) is likely to be required. By comparison,
if marked shunting or many lung units with low but not zero V Q  are the cause
of hypoxemia, a considerably higher FIO2 (e.g., >0.7) may be required, and even
this high FIO2 may not reverse the hypoxemia. A common practice when a
significant shunt is suspected is to give an FIO2 of 1.0, then adjust the FIO2
downward as guided by the resulting PaO2 or SaO2.
The O2 concentration that is toxic to the lungs in critically ill patients is not
known, but prior injury may provide tolerance to O2 toxicity, whereas other
conditioning agents, such as bleomycin, may enhance oxidative injury. An FIO2
of 0.7 or higher is generally considered injurious to the normal human lung.
Because it is unknown what lower concentration is safe, however, patients
should be given the lowest FIO2 that provides an adequate SaO2 (≥90%). If an
FIO2 equal to or greater than 0.5 to 0.7 is required for adequate oxygenation,
other measures, especially PEEP or CPAP, should be considered. Even a lower
FIO2 of about 0.5 may be associated with impaired ciliary action in the airways
and impaired bacterial killing by alveolar macrophages, but the clinical impor-
tance of these effects is not known.
A low concentration of supplemental O2 can be administered by nasal
prongs or nasal cannula, which most patients find comfortable and allows
them to cough, speak, eat, and drink while receiving O2. When the nasal pas-
sages are open, the PIO2 does not depend too much on whether the patient
breathes through the nose or the mouth because O2 is entrained from the
posterior nasal pharynx during a breath taken through the mouth. The level
of O2 can be adjusted by the flow rate to the nasal prongs. In patients with
COPD, flows as low as 0.5 to 2 L/minute are usually adequate unless an intra-
pulmonary shunt is contributing to the hypoxemia, as usually occurs in acute
pneumonia. At flows greater than approximately 6 L/minute, only a small
further augmentation in the PIO2 can be achieved. Because gas flow through
the nose has a drying and irritating effect, a face mask should be considered
at high flow rates. O2 face masks using the Venturi principle allow the regula-
tion of FIO2 and can be particularly useful when COPD is suspected, and it is
important to avoid the CO2 retention that can be associated with the unregu-
lated administration of O2. A higher FIO2 of 0.5 to nearly 1.0 can be adminis-
tered through a non-rebreathing face mask with an O2 reservoir. If an FIO2
equal to or greater than 0.70 is required for more than several hours, particu-
larly in an unstable patient, endotracheal intubation should be considered so
O2 can be administered by a closed system with reliable maintenance of the
patient’s SaO2. Indications for placing an artificial airway in a patient with acute
respiratory failure include airway protection against massive aspiration of
gastric contents, delivery of an increased FIO2, facilitation of prolonged
mechanical ventilation, and to aid in the control of respiratory secretions
(Chapter 105).
Ventilatory maneuvers that may increase arterial oxygenation include
mechanical ventilation itself and the administration of PEEP or CPAP, all of
which allow ventilation of areas of the lung that were previously poorly ven-
tilated or unventilated. Although large tidal volumes with mechanical ventila-
tion may open areas of atelectasis and may improve oxygenation initially,
these higher tidal volumes can cause lung injury, particularly if the lung is
already injured (Chapter 105).
CPAP refers to the maintenance of positive pressure during the respiratory
cycle while breathing spontaneously. PEEP refers to the maintenance of posi-
tive pressure throughout the expiratory cycle when it is applied together with
mechanical ventilation (Chapter 105). CPAP and PEEP can result in recruitment
of microatelectatic regions of the lung that are perfused but were not previ-
ously ventilated, thus contributing substantially to hypoxemia. CPAP and PEEP
have the theoretical advantage of keeping some of these regions open during
exhalation, thus preventing cyclic closure and reopening of lung units, which
can result in alveolar wall stress and injury.
Supportive Measures
Every patient with acute respiratory failure is at risk for deep vein thrombo-
sis, pulmonary thromboembolism, and gastric stress ulceration. Prophylactic
anticoagulation is recommended in patients who are not at high risk for bleed-
ing complications; sequential leg compression therapy may be preferred for
high-risk patients (Chapter 81).
The best means of preventing stress ulceration is not known, but current
evidence indicates that the use of an H2-blocker is superior to the gastric
administration of sucralfate, based on a large randomized, controlled trial that
found a higher incidence of significant bleeding in patients receiving sucral-
fate than in those receiving ranitidine. Evidence also indicates that proton
pump inhibitors may be useful in the acute care setting. There is little firm
evidence to guide nutritional management in patients with acute respiratory
failure (Chapters 221 and 224).
Current evidence supports maintaining the head of the bed at a 45-degree
angle to reduce aspiration in critically ill patients. Attempts should be made
to ensure a normal day-night sleep pattern, including minimizing activity and
reducing 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 can
enhance the removal of secretions, help maintain musculoskeletal function,
reduce the risk of deep vein thrombosis, and provide psychological benefits.
SPECIFIC ACUTE RESPIRATORY FAILURE
SYNDROMES
Chronic Obstructive Pulmonary Disease
EPIDEMIOLOGY AND PATHOBIOLOGY
The epidemiology and pathobiology of COPD are discussed in Chapter 88.
CLINICAL MANIFESTATIONS
When 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.
DIAGNOSIS
The 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.
TREATMENT
General Care
As 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;
decreased muscle strength or function, often related to electrolyte abnormali-
ties, including hypophosphatemia and hypomagnesemia; decreased chest
wall elasticity, possibly related to rib fracture, pleural effusion, ileus, or ascites;
atelectasis, pneumonia, or pulmonary edema; increased airway resistance,
caused by bronchospasm or increased secretions; or increased metabolic O2
requirements, such as with systemic infection. Many of these abnormalities
can impair the cough mechanism, diminish the clearance of airway secretions,
and precipitate acute respiratory failure.
Infection
The 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
influenzae and Streptococcus pneumoniae, and other acute pathogens is diffi-
cult to determine on a clinical or even microbiologic basis. Acute exacerba-
tions of COPD commonly result from new infections rather than re-emergence
of an infection from preexisting colonization. Antibiotics modestly shorten the
duration of the exacerbation, with no significant increase in toxicity, compared
with placebo; the impact of antibiotics on the subsequent emergence of resis-
tant organisms is not known. It is standard practice to use antibiotics to treat
a patient with COPD who has an exacerbation severe enough to cause acute
respiratory failure and who has evidence consistent with acute tracheobron-
chitis (Chapters 88 and 96). Pneumonia may account for 20% of cases of acute
respiratory failure in patients with COPD. Compared with the physiologically
normal population, patients with COPD who have community-acquired pneu-
monia are more likely to have gram-negative enteric bacteria or Legionella
infections and are more likely to have antibiotic-resistant organisms.
Other Precipitating Causes
Other common precipitating causes of acute respiratory failure include
heart failure and worsening of the underlying COPD, often related to noncom-
pliance with medications. Less common and often difficult to diagnose in this
setting is pulmonary thromboembolism.
 CHAPTER 104  ACUTE RESPIRATORY FAILURE
TABLE 104-4 KEY PRINCIPLES IN THE MANAGEMENT OF
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE PATIENTS WITH ACUTE RESPIRATORY
FAILURE
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.
Site of Care
Many patients with COPD and acute respiratory failure can be managed on
a general medical hospital floor rather than in an intensive care unit if the
precipitating cause of acute respiratory failure has been diagnosed and is
potentially responsive to appropriate therapy, if any blood gas abnormalities
respond to O2 therapy and are not life-threatening, if the patient can cooperate
with the treatment, and if appropriate nursing and respiratory care can be
provided (Chapter 88). An unstable patient who requires closer observation
and monitoring should be admitted to an intensive care unit.
Mechanical Therapy
The decision to use mechanical ventilation in patients with COPD and acute
respiratory failure must be made on clinical grounds and is not dictated by any
particular arterial blood gas values. In general, if the patient is alert and is able
to cooperate with treatment, mechanical ventilation is unlikely to be neces-
sary. If ventilatory support is required (Chapter 105), the decision is whether
to 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-pressure
ventilation is preferred for patients with COPD and can decrease mortality if
applied in appropriate patients with no factors that are likely to lead to
complications. 3  involving most of the lungs, or whether localized pneumonia has precipitated
635
TABLE 104-5 DISORDERS ASSOCIATED WITH ACUTE LUNG
INJURY AND ACUTE RESPIRATORY DISTRESS
SYNDROME
COMMON
Sepsis (gram-positive or gram-negative bacterial, viral, fungal, or parasitic infection)
Diffuse pneumonia (bacterial, viral, or fungal)
Aspiration of gastric contents
Trauma (usually severe)
LESS COMMON
Near-drowning (fresh or salt water)
Drug overdose
Acetylsalicylic acid
Heroin 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 reactions
Inhalation of smoke or corrosive gases (usually requires high concentrations)
Pancreatitis
Fat embolism
UNCOMMON
Miliary tuberculosis
Paraquat poisoning
Central nervous system injury or anoxia (neurogenic pulmonary edema)
Cardiopulmonary bypass
PROGNOSIS
Acute 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
DEFINITION
ARDS 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.
EPIDEMIOLOGY
Acute 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.
ETIOLOGY
Acute 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
a sepsis syndrome, with secondary injury to other parts of the lung.
636 CHAPTER 104  ACUTE RESPIRATORY FAILURE
 

PATHOBIOLOGY TABLE 104-6 FEATURES ASSOCIATED WITH

Pathology NONCARDIOGENIC AND CARDIOGENIC
Despite the variety of underlying disease processes leading to acute lung PULMONARY EDEMA*
injury, the response to these insults in the lung is monotonously characteris- CARDIOGENIC EDEMA/VOLUME
tic, with similar clinical findings, physiologic changes, and morphologic NONCARDIOGENIC EDEMA (ARDS) OVERLOAD
abnormalities. The pathologic abnormalities in acute lung injury and ARDS
PRIOR HISTORY
are nonspecific and are described as diffuse alveolar damage by pathologists.
The initial process is inflammatory, with neutrophils usually predominating Younger Older
in the alveolar fluid. Hyaline membranes develop, similar to those seen in No history of heart disease Prior history of heart disease
premature infants with infant respiratory distress syndrome, presumably Appropriate fluid balance (difficult to Hypertension, chest pain, new-onset
related to the presence of large-molecular-weight proteins that have leaked assess after resuscitation from shock or palpitations; positive fluid balance
into the alveolar space. Alveolar flooding leads to impairment of surfactant, trauma)
which is abnormal in quantity and quality. The result is microatelectasis, PHYSICAL EXAMINATION
which may be associated with impaired immune function. Cytokines and
Flat neck veins Elevated neck veins
other inflammatory mediators are usually markedly elevated, although with
different patterns over time in the bronchoalveolar lavage fluid and the sys- Hyperdynamic pulses Left ventricular enlargement, lift, heave,
dyskinesis
temic blood. Lung repair is also disturbed; early evidence of pro-fibrotic
processes includes the appearance of breakdown products of pro-collagen in Physiologic gallop S3 and S4; murmurs
the bronchoalveolar lavage fluid, followed by scarring. The pulmonary fibro- Absence of edema Edema: flank, presacral, legs
sis observed on lung biopsy or at autopsy is identical to that seen in patients ELECTROCARDIOGRAM
with idiopathic pulmonary fibrosis (Chapter 92). Because lung function
Sinus tachycardia, nonspecific ST-T wave Evidence of prior or ongoing ischemia,
improves over time in survivors of ARDS, however, it has been assumed that changes supraventricular tachycardia, left
this scarring is often reversible. ventricular hypertrophy

Pathophysiology CHEST RADIOGRAPH

The physiologic abnormalities are dominated by severe hypoxemia with Normal heart size Cardiomegaly
shunting, decreased lung compliance, decreased functional residual capacity, Peripheral distribution of infiltrates Central or basilar infiltrates;
and increased work of breathing. Initially, the Paco2 is low or normal, usually peribronchial and vascular congestion
associated with increased alveolar ventilation. The initial abnormalities in Air bronchograms common (80%) Septal lines (Kerley’s lines), air
oxygenation are thought to be related to alveolar flooding and collapse. As bronchograms (25%), pleural effusion
the disease progresses, especially in patients who require ventilatory support, HEMODYNAMIC MEASUREMENTS
fibroproliferation develops; the lungs (including alveoli, blood vessels, and
Pulmonary artery wedge pressure Pulmonary capillary wedge pressure
small airways) remodel and scar, with a loss of microvasculature. These <15 mm Hg, cardiac index >3.5 L/ >18 mm Hg, cardiac index <3.5 L/
changes may lead to pulmonary hypertension and increased dead space; min/m2 min/m2 with ischemia, may be
marked elevations in minute ventilation are required to achieve a normal >3.5 L/min/m2 with volume overload
Paco2, even as oxygenation abnormalities are improving. *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
CLINICAL MANIFESTATIONS predictive value.
ARDS = acute respiratory distress syndrome.
In 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- cause of ventilator-induced lung injury, even when adequate oxygenation
trates or opacities on the chest radiograph. Alternatively, it may be dominated can be obtained at relatively low levels of FIO2. The early use of cisatracurium
by manifestations of the underlying disease process, such as severe sepsis with besylate (15 mg rapid infusion followed by 37.5 mg/hr for 48 hours), a neuro-
muscular blocker, can reduce ARDS mortality rates by about 25%. 6  In patients
hypotension and other manifestations of systemic infection.
with severe ARDS who do not respond to standard therapy but otherwise have
a reasonable life expectancy, extracorporeal membrane oxygenation can
DIAGNOSIS improve the 6-month survival from 47 to 63% at an acceptable cost of about
The key to diagnosis is to distinguish ARDS from cardiogenic pulmonary $35,000 per quality-adjusted year of life saved. 7 
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.

Acute Respiratory Failure without Lung Disease

TREATMENT
Treatment for acute lung injury and ARDS consists predominantly of respi-
ratory support and treatment of the underlying disease (Fig. 104-4). Although
sepsis is a common predisposing condition for the development of acute lung
injury, a small study examining the usefulness of activated protein C in patients
with acute lung injury did not demonstrate any beneficial effects in terms of
ventilator-free days or mortality.
Mechanical Therapy
Current recommendations for mechanical ventilation via endotracheal intu-
bation (Table 104-7) emphasize lower tidal volumes based on the patient’s
predicted body weight (Chapter 105). 4  PEEP is a mainstay in the ventilatory
strategy for acute lung injury; although the method for determining the
optimal level of PEEP has not been established, higher PEEP levels appear to
benefit patients with ARDS. 4,5  PEEP may allow a lower FIO2 to provide ade-
quate oxygenation, thus avoiding O2 toxicity. It also may prevent the cyclic
collapse and reopening of lung units, a process that is thought to be a major
Acute 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.
 CHAPTER 104  ACUTE RESPIRATORY FAILURE
 
637

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%

Yes No

Adjust FIO2 to yield SaO2 88-95% Intubate: volume cycled ventilation: VT 6 mL/kg
Consider NIPPV to relieve dyspnea PBW; FIO2 1.0; PEEP 5 cm H2O assist
control mode; conscious sedation and
maintain comfort
Code status discussed; NPO; H2 blocker; DVT
SaO2<88%
prophylaxis; semi-recumbent (45°) position

SaO2>95%
Increase PEEP in 3-5 cm H2O increments
(or consider ARDSNet PEEP/FIO2 ladder)
Reduce FIO2 until
FIO2<0.6
SaO2<96%
Monitor ABG, blood pressure, urine output,
capillary refill time, and (if available)
cardiac index FIO2£0.6
Inadequate perfusion Adequate perfusion

Give volume Measure plateau

pressure Maintain urine output@fluid intake 24-48 h
Consider right heart catheterization

£30 cm H2O >30 cm H2O

Continue to increase PEEP by 3-5 cm H2O Decrease VT by 1 mL/kg PBW decrements
increments; repeat above assessment until (to minimum of 4) until Pplat<30 cm H2O;
SaO2>88% and FIO2<0.6 allow PaCO2 to rise slowly
Consider other modes of ventilatory support
Note: If chest wall compliance is markedly
decreased (e.g., massive ascites), then it
may not be necessary to decrease VT

Repeat ABG

SaO2>95% or SaO2 88-95% or SaO2<88% or

PaO2>80 mm Hg PaO2 55-80 mm Hg PaO2<55 mm Hg

Decrease FIO2 by 0.1 decrements to 0.4 Maintain ventilator settings Increase PEEP by 3-5 cm H2O increments
and/or decrease PEEP by 3-5 cm H2O to Continue pulse oximetry; to maximum of 25 cm H2O and/or
8 cm H2O (or consider ARDSNet repeat ABG in 4-8 h or increase FIO2 by 0.1 increments to 1.0
PEEP/FIO2 ladder) as clinically indicated
Repeat assessment of plateau pressure
Wean from ventilator as tolerated
and ABG

SaO2 remains<88%
PaO2 remains<55 mm Hg

Consider prone position; increase sedation

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

FIGURE 104-4.  Algorithm for the initial management of acute respiratory distress syndrome. ABG = arterial blood gas analysis; CO2 = carbon dioxide; DVT = deep vein thrombosis;
FIO2 = inspired oxygen concentration; MSOF = multisystem organ failure; NIPPV = noninvasive intermittent positive-pressure ventilation; O2 = oxygen; PaCO2 = arterial partial pressure
of carbon dioxide; PaO2 = arterial partial pressure of oxygen; PBW = predicted body weight; PEEP = positive end-expiratory pressure; Pplat = plateau pressure; RR = respiratory rate;
SaO2 = arterial oxygen saturation; VT = tidal volume.
 TABLE 104-7 ARDSNet VENTILATORY MANAGEMENT
PROTOCOL FOR TIDAL VOLUME AND PLATEAU
PRESSURE
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 mode
Set initial VT at 8 mL/kg PBW
Reduce VT by 1 mL/kg at intervals < 2 hr until VT = 6 mL/kg PBW
Set 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
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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.