Edema Pulmoner 2
Edema Pulmoner 2
Edema Pulmoner 2
pulmonary artery. The increase in pulmonary vascu- Gas Exchange. Pulmonary Vascular Remodeling.
lar resistance caused by the narrowing of the artery Smooth Muscle Cells: Vascular. Ventilation: Uneven.
results in right ventricular hypertension. Stenoses in Ventilation, Perfusion Matching.
the left heart valves lead to passive pulmonary ve-
nous hypertension. The elevation in venous pressure
results in elevated capillary and arterial pressures.
Further Reading
Bakhle YS and Vane JR (1974) Pharmacokinetic function of the
Pulmonary Embolism pulmonary circulation. Physiological Reviews 54(4): 1007–1045.
Crofton J and Douglas A (eds.) (1975) The pulmonary circulation.
Pulmonary embolism is perhaps the most common In: Respiratory Diseases, 2nd edn., pp. 34–37. Philadelphia:
pulmonary vascular disease. Clots originate in the Lippincott Co.
systemic veins, often in the deep veins of the lower Crystal RG, West JB, Weibel ER, and Barnes PJ (eds.) (1997) The
extremities, and formation is augmented following Lung: Scientific Foundations, 2nd edn., sect. 5. New York:
injury, venous stress, and hypercoagulable states. The Lippincott-Raven.
Dawson CA (1984) Role of pulmonary vasomotion in physiology
thrombi detach and become lodged in the pulmonary of the lung. Physiological Reviews 64(2): 544–616.
arterial circulation. Occasionally, the right side of Hlastala MP and Glenny RW (1999) Vascular structure determines
the heart is a source of a pulmonary embolus. Given pulmonary blood flow distribution. News in Physiological Sci-
the large reserve capacity of the pulmonary capillar- ences 14: 182–186.
ies, many thromboemboli can go undiagnosed, and Keith IM (2000) The role of endogenous lung neuropeptides in
regulation of the pulmonary circulation. Physiological Research
resolve quickly. Massive blockages produce a func- 49(5): 519–537.
tional decrease in cross-sectional area of the pulmo- McMurtry IF (1986) Humoral control. In: Bergofsky EH (ed.)
nary circulation, resulting in a significant increase in Abnormal Pulmonary Circulation, pp. 83–125. New York:
pulmonary vascular resistance and elevated pulmo- Churchill-Livingstone.
Nadel JF and Nadel JA (eds.) (1988) Textbook of Respiratory
nary arterial pressure. Subsequent right ventricular
Medicine. Philadelphia: WB Saunders.
strain decreases cardiac output and, if severe, can Peacock AJ (ed.) (1966) Pulmonary Circulation. London: Chap-
result in death. In approximately one-tenth of pa- man and Hall Medical.
tients, large thromboemboli cause local cessation of Sylvester JT and Brower RG (1990) Pulmonary blood flow. In:
flow and ischemic necrosis of the lung parenchyma Stein JH (ed.) Internal Medicine, 3rd edn., pp. 583–586. Boston:
(pulmonary infarction). Little, Brown and Co.
Ward JPT and Aaronson PI (1999) Mechanisms of hypoxic pul-
monary vasoconstriction: can anyone be right? Respiratory
See also: Bronchial Circulation. Diffusion of Gases. Physiology 115(3): 261–271.
Endothelial Cells and Endothelium. High Altitude, West JB, Dollery CT, and Naimark A (1964) Distribution of blood
Physiology and Diseases. Hypoxia and Hypoxemia. flow in isolated lung: relation to vascular and alveolar pressures.
Oxygen–Hemoglobin Dissociation Curve. Peripheral Journal of Applied Physiology 19: 713–724.
PULMONARY EDEMA
M A Matthay and T E Quinn, University of California, fluid is removed via active transport mechanisms. Pulmonary
San Francisco, CA, USA edema occurs because of either increased hydrostatic forces or
increased vascular permeability which then causes an increase in
& 2006 Elsevier Ltd. All rights reserved. fluid filtration sufficient to overwhelm fluid removal mecha-
nisms. The treatment of hydrostatic pulmonary edema targets a
reduction in pulmonary microvascular pressure with diuretics,
Abstract vasodilators, and sometimes inotropic agents. The treatment of
Pulmonary edema refers to the abnormal collection of fluid in increased permeability pulmonary edema is mainly supportive.
the extravascular spaces of the lung such as the interstitium and Mechanical ventilation of patients with increased permeability
the alveoli. Its two main pathophysiologic mechanisms are in- pulmonary edema should be performed with a low tidal volume,
creased hydrostatic forces within the lung microvasculature and lung-protective strategy.
increased microvascular permeability. Understanding the patho-
physiology of pulmonary edema requires a firm understanding
of normal lung fluid balance. The Starling equation, which de- Introduction
scribes the net flow of fluid across a semipermeable membrane,
applies to the filtration of fluid from the pulmonary micro- Pulmonary edema refers to the abnormal collection
vasculature into the pulmonary interstitium. Interstitial fluid is of fluid in the extravascular spaces of the lung such
primarily removed by the lung lymphatic vessels, and alveolar as the interstitium and the alveoli. Its two main
PULMONARY EDEMA 545
pathophysiologic mechanisms are increased hydro- of lung fluid clearance, which are less important un-
static forces within the lung microvasculature and der normal conditions, include filtration through the
increased microvascular permeability. Pulmonary ed- visceral pleura into the pleural space, and movement
ema from either mechanism may lead to profoundly of fluid via the loose peribronchovascular connective
diminished lung function, respiratory distress, and tissue into the mediastinum.
even death. Under pathological conditions in which excess
fluid is filtered into the pulmonary interstitium, the
above described mechanisms become safety factors
Normal Lung Fluid Balance against the development of pulmonary edema and
Starling Forces alveolar flooding. The lymphatic system’s rate of
liquid clearance can increase up to 10 times normal
Understanding the mechanisms of pulmonary edema
when hydrostatic forces increase. Second, as in-
formation requires a firm understanding of normal
creased fluid is filtered into the perimicrovascular
lung fluid balance. The Starling equation describes
space, pressure in that space (Pmv) increases and pro-
the net flow of fluid across a semipermeable mem-
tein concentration falls (decreased pi). These changes
brane. Applied to the lung microvasculature, it can
in the perimicrovascular space oppose further fluid
be written as follows:
accumulation. Third, the loose peribronchovascular
Qf ¼ K½ðPmv Pi Þ sðpmv pi Þ connective tissue has a high capacitance, allowing a
large amount of fluid accumulation (up to 500 ml)
where Qf is the net filtration of fluid from the lung before tissue pressure rises. Finally, if fluid accumu-
microvasculature to the interstitium, K is the filtra- lation in the pulmonary interstitium continues, pres-
tion coefficient or leakiness of the endothelium to sure in that space will increase enough to allow
water, Pmv is the pulmonary microvascular pressure, filtration across the visceral pleura and the formation
Pi is the pulmonary interstitial pressure, s is the pro- of a pleural effusion. A large amount of fluid can
tein reflection coefficient, pmv is the protein osmotic sequester in the pleural space before lung function is
pressure in the microvasculature, and pi is the inter- sufficiently diminished to impact gas exchange.
stitial protein osmotic pressure. Under normal con-
ditions, the microvascular endothelium is somewhat Alveolar fluid clearance In the presence of intersti-
leaky to fluid, and the pulmonary interstitial pressure tial pulmonary edema, the alveoli are protected from
is slightly negative. On the other hand, the endothe- flooding by two main mechanisms. In contrast to the
lium is quite impermeable to proteins with a reflec- relatively leaky microvascular endothelium, the al-
tion coefficient near 1. Thus, the fluid filtered from veolar epithelium has tight junctions which render it
the micro vessels is low in protein compared to the quite impermeable to interstitial fluid and protein.
fluid in the vascular space. On balance, there is nor- However, if edema fluid accumulation exceeds the
mally a small net flow of fluid from the lung micro- capacity of the interstitial clearance mechanisms for
vasculature to the interstitium. long enough, the alveolar epithelial barrier changes,
and alveolar flooding occurs. If the edema is formed
Lung Fluid Clearance and Protective Mechanisms
from increased hydrostatic pressure, the alveoli are
Interstitial fluid clearance As described above, fluid flooded with edema fluid that has a low protein con-
is filtered into the lung interstitium from the micro- centration relative to plasma. If the edema is caused
vasculature under normal conditions. This fluid must by increased permeability (acute respiratory distress
be constantly removed to maintain homeostasis. The syndrome (ARDS)), the alveoli are flooded with
most important mechanism for lung fluid removal is protein-rich fluid. In either case, alveolar fluid clear-
the lung lymphatic system. The pulmonary inter- ance then becomes vital to the restoration of lung
stitium is rich with lymphatic channels which absorb function.
filtered fluid and protein and convey it along chan- Alveolar fluid clearance occurs primarily by active
nels in the interlobular septa to the mediastinal lym- sodium transport. The alveolar type II cells are prob-
phatic vessels. Another mechanism of fluid removal ably responsible for most of the active sodium trans-
from the lung under normal conditions is the direct port out of the alveolus. Sodium is transported into
reabsorbtion of fluid into the pulmonary venules. the type II cell via an amiloride-sensitive epithelial
Since the normal filtered fluid is low in protein (low sodium channel (ENaC) on the apical surface. The
pi) and the intravascular fluid is protein rich (high oubain-sensitive Na–K ATPase on the basolateral
pmv), Starling forces along the venules, where intra- membrane surface then transports the sodium out
vascular hydrostatic pressure (Pmv) is normally low, of the cell. As an osmotic gradient forms, water
will favor reabsorbing fluid. Two other pathways flows out of the alveolus, possibly via water channels
546 PULMONARY EDEMA
called aquaporins. In this fashion, water is rapidly Table 1 Clinical disorders associated with acute lung injury
cleared from flooded alveoli. Direct Indirect
Pneumonia Sepsis
Pulmonary Edema Pathogenesis Aspiration Nonthoracic trauma
Thoracic trauma Acute pancreatitis
Pulmonary edema forms from two main mecha- Inhalation injury Drug overdose
nisms, increased microvascular pressure (Pmv) and Fat emboli Transfusion associated (TRALI)
increased microvascular permeability. The most com- Near drowning Cardiopulmonary bypass
Reperfusion after transplant Burns
mon reason for increased Pmv is elevated left atrial or embolectomy
pressure (cardiogenic pulmonary edema). The most
common reasons for elevated left atrial pressure in-
clude severe volume overload, left ventricular systolic an acute upper airway obstruction such as post-
dysfunction, left ventricular diastolic dysfunction, anesthesia laryngospasm. A patient with an acutely
mitral valve disease, and aortic valve disease. A full obstructed upper airway will make very vigorous
discussion of all of the etiologies of cardiogenic pul- respiratory effort leading to markedly negative intra-
monary edema is beyond the scope of this article. thoracic pressures, which are transmitted to the peri-
Nevertheless, all of these disorders cause pulmonary microvascular interstitium (decreased Pi from the
edema via the same pathophysiologic mechanism, Starling equation). Also, large negative intrathoracic
that is, increased microvascular pressure causing in- pressures increase both preload and afterload on the
creased fluid filtration into the interstitium. If the heart. The increased preload and afterload probably
resultant edema fluid accumulation is confined to the increase pulmonary microvascular pressure (Pmv).
interstitium by the safety factors described above, Thus, there are increased net hydrostatic forces,
then only mild, if any, symptoms will result. How- and edema forms. Neurogenic pulmonary edema is
ever, if increased microvascular pressure is severe thought to occur because of the massive catechola-
or persists, then the defense mechanisms are over- mine surge produced after a neurologic event. This
whelmed, alveolar flooding ensues, and gas exchange surge causes marked systemic vasoconstriction and
is impaired. Because the capillary endothelium and redistribution of blood from the systemic to pulmo-
alveolar epithelium remain intact, the edema fluid nary circulation. The resulting increased pulmonary
suctioned out of the airway has a low protein content vascular pressures may produce a hydrostatic pulmo-
compared with plasma (ratio of p0.65). nary edema (low protein) or lead to physical damage
Increased vascular permeability (increased K and to the vascular walls. This latter scenario causes an
decreased s from the Starling equation) is caused by increased permeability edema. Similarly, HAPES may
damage to the endothelium and alveolar epithelium. result from severe, nonhomogeneous pulmonary vaso-
When this occurs, both the interstitium and alveoli constriction. The vasoconstricted areas shunt blood
are flooded with protein-rich fluid (edema fluid to flow to other areas of the lung leading to increased
plasma protein concentration ratio 40.65). Because Pmv in the perfused areas. Again, a low-protein hy-
of the damage to the alveolar epithelium, alveolar drostatic edema may result, or there may be damage
fluid clearance is usually impaired. Gas exchange is to the endothelium from the increased pressure caus-
usually significantly diminished. Increased permea- ing high-protein, increased-permeability edema.
bility pulmonary edema is also known as acute lung
injury, or, in its severest form, ARDS (see Acute Res-
piratory Distress Syndrome). There are numerous Diagnosis
causes of acute lung injury, the most common of
Hydrostatic Pulmonary Edema
which are listed in Table 1. These causes of acute
lung injury may be grouped into those that constitute The vast majority of cases of hydrostatic pulmonary
a direct insult to the alveolar epithelium such as as- edema are of cardiac origin. The diagnosis rests
piration of gastric contents or pneumonia, and those heavily on the history, physical examination, and
that are an indirect insult to the alveolar epithelium chest radiography. Most patients with acute pulmo-
such as sepsis. nary edema of any cause will present with dyspnea
Some less common types of pulmonary edema in- in which case the history of present illness should
clude postobstructive pulmonary edema (see Upper focus on dyspnea severity, time of onset, pace of
Airway Obstruction), neurogenic pulmonary edema, onset, and associated symptoms. Patients with
and high-altitude pulmonary edema (HAPES) (see acute cardiogenic pulmonary edema may have sud-
High Altitude, Physiology and Diseases). Postob- den, severe dyspnea. Because a significant number of
structive pulmonary edema occurs in the setting of these severely affected patients have pulmonary
PULMONARY EDEMA 547
edema secondary to an acute coronary event, one above, acute pulmonary edema is often associated
should thoroughly question the patient or family with an acute coronary event, so an electrocardio-
about chest pain or angina equivalents. Patients may gram should be performed in all patients with
also give a history of recently worsening chronic suspected acute cardiogenic pulmonary edema. Par-
congestive heart failure symptoms such as worsening ticular attention should be paid to electrocardio-
dependent edema, orthopnea, and paroxysmal noc- graphic signs of ischemia or infarction such as ST
turnal dyspnea. A history of dietary indiscretion is segment elevation, severe ST segment depression, new
common in patients with an acute exacerbation of Q waves, or a new left bundle branch block. Like-
chronic congestive heart failure. The past medical wise, creatine phosphokinase-MB (CPK-MB) and
history should focus on prior history of coronary ar- troponin levels are useful in patients with suspected
tery disease, valvular heart disease, hypertension, or cardiogenic pulmonary edema to rule out myocardial
cardiomyopathy. infarction. Blood levels of B-type natriuretic peptide
On physical examination, patients with acute (BNP) are useful in emergency department patients
cardiogenic pulmonary edema may be very anxious with dyspnea and suspected cardiogenic pulmonary
and sitting ‘bolt upright’ in bed. In the most severe edema, however, their diagnostic accuracy in inpa-
cases, patients may develop cyanosis, the develop- tients is unproven. Arterial blood gases are useful in
ment of which signifies severe respiratory failure and assessing the severity of respiratory compromise. In-
impending death if not corrected quickly. Other signs terstitial pulmonary edema may be associated with
include jugular venous distension, an S3 gallop on normal or slightly reduced oxygenation (decreased
heart examination, pitting edema, a palpable liver PaO2) with a reduced PaCO2 from tachypnea. With
edge, and ascites. The respiratory examination is alveolar flooding, significant intrapulmonary shunt
characterized by the presence of wet rales, possible develops, and a markedly reduced PaO2 will result if
extending up to the apices of the lung. Patients may untreated. Echocardiography may be very helpful in
also exhibit the use of accessory respiratory muscles. determining the etiology of pulmonary edema. Nor-
Chest radiography is valuable in diagnosing pul- mal echocardiographic structure and function argue
monary edema. In cardiogenic pulmonary edema, the strongly against pulmonary edema of cardiac origin.
heart silhouette is often enlarged. If only interstitial Finally, pulmonary artery catheterization may pro-
edema is present, there may be evidence of apical vide valuable information in patients with pulmonary
vascular engorgement (so-called vascular redistribu- edema and shock. Not only can normal pulmonary
tion), septal or Kerley’s lines, and decreased defini- artery occlusion pressures exclude cardiogenic pul-
tion of smaller blood vessels and bronchial structures monary edema, but the clinician can follow trends in
(perivascular and peribronchial cuffing). When alve- the pulmonary artery catheter data to help guide fluid
olar flooding occurs, confluent parenchymal opaci- and vasopressor management.
ties develop. In hydrostatic edema, the radiographic
opacities often develop centrally first. In severe cases,
Increased Permeability Pulmonary Edema
there may be complete opacification bilaterally with
air bronchograms. Chest radiography cannot reliably Increased permeability pulmonary edema is also
distinguish between hydrostatic pulmonary edema known as ALI or ARDS in its severest form. Cur-
and increased permeability pulmonary edema (acute rently, its diagnosis is based on a set of criteria as set
lung injury (ALI)). forth by the American–European Consensus Confer-
Several other diagnostic tests may be useful in ence on Acute Respiratory Distress Syndrome (see
patients with dyspnea or respiratory distress and sus- Table 2) (see Acute Respiratory Distress Syndrome).
pected cardiogenic pulmonary edema. As mentioned These criteria identify a patient population with
Table 2 Diagnostic criteria for acute lung injury (ALI) acute respiratory distress syndrome (ARDS)
hypoxemia and bilateral infiltrates on chest radio- accompany ALI. Another potential advantage of
graph whose condition cannot be explained by in- pulmonary artery catheterization is that the hemo-
creased left atrial pressure (noncardiogenic). Based dynamic data may be useful in guiding fluid and
on these criteria, the most useful data in the diagnosis vasopressor therapy. However, the benefit of routine
of acute lung injury are the history, chest radiograph, use of pulmonary artery catheters in ALI patients is
and arterial blood gases. not well established, and this issue is the subject of an
The history in suspected ALI should focus on elic- ongoing multicenter, randomized, controlled trial.
iting the presence of one of the common causative
conditions (see Table 1). In postoperative patients, a
thorough examination of the anesthesia record for Management
blood products transfused or witnessed aspiration
Cardiogenic Pulmonary Edema
during induction or recovery is helpful. On lung ex-
amination, patients with ALI may have bilateral rales Some patients with mild cardiogenic pulmonary ed-
or evidence of consolidation, but these findings ema can be treated and released from the emergency
are non-specific. Thus, the physical examination in department with close follow-up. However, patients
suspected ALI patients should be directed toward with new onset or severe symptoms, hypoxia, evi-
determining whether the patient’s edema can be ex- dence of acute ischemia, or poor follow-up should
plained by elevated left atrial pressure and whether be admitted to the hospital for treatment and mon-
the patient has one of the potential causes of ALI. itoring. Indications for intensive care unit admission
The absence of any history or physical examination will vary with each facility’s capability, but patients
evidence for volume overload or congestive heart with profound hypoxia, need for ventilatory support,
failure in a patient with pulmonary edema strongly or need for invasive monitoring should be admit-
suggests ALI. In addition, the patient’s abdomen, ted to a critical care unit. Pulse oximetry should be
rectum, and skin should be meticulously examined monitored early in all patients who present with
for a potential source of sepsis. dyspnea, and patients with significant hypoxia or
As indicated by the diagnostic criteria, the chest at risk for worsening should have continuous pulse
radiograph and arterial blood gases are the most use- oximetry. Patients with a suspected ischemic cause of
ful diagnostic tests in ALI. The chest radiograph may their pulmonary edema should have continuous elec-
show only bilateral interstitial edema, but most likely trocardiographic monitoring also. An arterial cathe-
it will demonstrate areas of alveolar filling. More ter should be placed in patients receiving nitroprus-
severe cases may show extensive consolidation of side for severe cardiogenic pulmonary edema with
both lungs. Because pneumonia is the most common hypertension and patients receiving vasopressors
cause of ALI, there also may be focal consolidation for shock. Also, mechanically ventilated patients re-
with air bronchograms. By definition, arterial blood quiring frequent arterial blood gases may benefit
gas analysis will demonstrate significant hypoxia and from an arterial catheter. Pulmonary artery catheter-
intrapulmonary shunt. A respiratory alkalosis may be ization for hemodynamic monitoring may be useful
present early in the course of ALI due to hypoxic in patients with severe cardiogenic pulmonary edema
respiratory drive and/or sepsis, but later respiratory and shock, but its use is controversial.
acidosis may develop from worsening lung compli- Supportive care for patients with cardiogenic pul-
ance and increased dead space. In addition, hypoxia monary edema includes oxygen supplementation and
and sepsis may cause a metabolic acidosis. Other support of ventilation if necessary. Noninvasive ven-
laboratory tests should be directed at potential causes tilation initiated early in patients with severe hypoxia
of ALI. Because sepsis and pneumonia are the most or respiratory distress may prevent the need for
common causes of ALI, cultures of blood, sputum (or mechanical ventilation. This modality may not be
airway aspirate), urine, wounds, and, if appropriate, appropriate for patients with an acute coronary syn-
cerebrospinal fluid should be obtained. Abdominal drome, since it may not reduce the work of breathing
tenderness on examination should be evaluated with and myocardial oxygen demand as much as intubat-
imaging studies and amylase and lipase levels. ion and mechanical ventilation. Intubation and me-
Other possible diagnostic studies in ALI include chanical ventilation is required in patients whose
pulmonary artery catheterization and echocardiog- hypoxia or respiratory distress is refractory to non-
raphy. Both of these modalities can be useful in de- invasive ventilation or who require rapid reduction
termining whether the pulmonary edema is due to a in work of breathing.
cardiogenic source. Pulmonary artery catheterization Pharmacotherapy in cardiogenic pulmonary edema
may also provide valuable diagnostic information is aimed at reducing pulmonary microvascular pres-
about the etiology of shock states which frequently sure (Pmv from the Starling equation) and reducing
PULMONARY EDEMA 549
dyspnea. If there is an underlying cause of the cyclic AMP, which increases intracellular calcium.
acute pulmonary edema such as acute myocardial These agents also cause peripheral vasodilation
infarction, it must be treated aggressively. The reduc- and reduction in blood pressure, so blood pressure
tion in pulmonary microvascular pressure is primarily should be closely monitored upon initiation of
achieved by vasodilating medications and diuretics. milrinone. Like the adrenergic agonists, milrinone
Loop diuretics such as furosemide are the most has been associated with increased ventricular ectopy.
commonly used diuretics in acute cardiogenic pul- Levosimendan is a novel inotropic agent currently
monary edema because of their rapid onset and undergoing clinical trials. Its mechanism of action,
effectiveness in producing intravascular volume re- calcium sensitization of cardiac myocytes, may
duction. They even have a small, venodilating effect avoid some of the adverse effects of adrenergic
which may slightly decrease pulmonary microvascu- agonists and phosphodiesterase inhibitors. Overall,
lar pressure immediately. However, even with the the use of inotropic agents in acute cardiogenic pul-
rapid onset of diuresis provided by furosemide, monary edema has not been shown to improve mor-
patients with severe acute cardiogenic pulmonary tality, and they are associated with potentially serious
edema will need other medications that work more adverse effects. Inotropic agents should therefore not
quickly to reduce pulmonary microvascular pressure, be routinely used in patients with acute cardiogenic
namely vasodilating agents. In addition to its useful- pulmonary edema.
ness in relieving dyspnea, morphine has venodilating
effects which act to increase peripheral blood pool-
Permeability Pulmonary Edema
ing. This pooling reduces left ventricular end diastolic
pressure, and thereby pulmonary microvascular pres- For practical purposes, permeability pulmonary ed-
sure is reduced. Nitroglycerin and nitroprusside are ema and ALI are the same. ARDS is the most severe
two agents that provide immediate vasodilation and form of ALI. The large majority of cases of ALI will
can be given as a titratable intravenous infusion. Ni- be treated in intensive care units either because of the
troglycerin causes both arterial and venous dilation, severity of the hypoxia and respiratory distress or be-
although venodilation is the more profound effect. Its cause of the severity of the causative disorder such as
dilation of epicardial coronary arteries may also play sepsis. Pulse oximetry should be monitored frequently
a role in its antianginal effect. Nitroprusside has more or continuously in ALI patients, because they are at
prominent arterial dilating effects. Both of these high risk of respiratory decompensation. An arterial
agents produce a rapid reduction in cardiac preload catheter for frequent blood gas analysis is helpful, es-
and afterload with consequent reduction in pulmo- pecially in intubated patients or patients at high risk
nary microvascular pressure. Finally, nesiritide is re- of intubation. The relative benefit of a central venous
combinant human B-type natriuretic peptide. Despite catheter versus a pulmonary artery catheter for cen-
its name, its dominant clinical action seems to be tral venous pressure monitoring is currently under
vasodilation instead of natriuresis. Nesiritide has study in a multicenter, randomized, clinical trial.
been evaluated for use in acute cardiogenic pulmo- Since there is no specific pharmacotherapy for ALI,
nary edema, but there is little evidence that its in- the mainstays of management are treatment for the
creased cost compared with nitroglycerin is justified underlying condition and supportive care. Unless
by increased benefit. there is a clear noninfectious cause of ALI, most pa-
When cardiogenic pulmonary edema is refractory tients should be treated with broad-spectrum anti-
to the usual measures described above, or when it is biotics intitially. Source control, such as drainage of
accompanied by cardiogenic shock, inotropic agents abscesses, should be performed urgently.
may provide short-term improvement. The currently Supportive care usually includes intubation and
available inotropes fall into two categories, b-ad- mechanical ventilation. Importantly, the method of
renergic agonists and phosphodiesterase inhibitors. mechanical ventilation is the only specific treatment
The most commonly used adrenergic agonist in for ALI. A mechanical ventilation regimen with low
cardiogenic pulmonary edema is dobutamine. It stim- tidal volume (6 ml kg 1 based on ideal body weight),
ulates cardiac b1-adrenergic receptors causing in- plateau pressures of less than 30 cm water, and a
creased inotropy and chronotropy. The chief side moderate level of positive end-expiratory pressure
effects are tachycardia and increased ventricular ec- has been shown to significantly reduce mortality in
topy. In addition, dobutamine may cause vasodilation ALI patients (see Table 3). In attempting to reach
and hypotension because of its stimulation of b2 these goals, a pH as low as 7.25 and PaO2 as low as
receptors in vascular smooth muscle. Phosphodiest- 55 mmHg are usually tolerated. Thus, unless there is
erase inhibitors, such as milrinone, produce their a contraindication to the permissive hypercapnea
inotropic effect by increasing cardiac intracellular (such as elevated intracranial pressure) or permissive
550 PULMONARY EFFECTS OF SYSTEMIC DISEASE
Table 3 Protocol for low tidal volume ventilation for acute lung injury
Variables Protocol
hypoxemia (such as an acute coronary syndrome), all Brower RG, Lanken PN, MacIntyre N, et al. (2004) Higher versus
patients who meet the diagnostic criteria for ALI lower positive end-expiratory pressures in patients with the
should be ventilated with the low tidal volume strat- acute respiratory distress syndrome. New England Journal of
Medicine 351(4): 327–336.
egy. Nutritional support should be considered early, Gehlbach BK and Geppert E (2004) The pulmonary manifestations
because many ALI patients will have a prolonged of left heart failure. Chest 125: 669–682.
ventilator course. Current clinical trials in patients Givertz MM, Colucci WS, and Braunwald E (2001) Clinical as-
with ALI are investigating possible pharmacologic pects of heart failure: high output heart failure; pulmonary ed-
agents such as activated protein C and granulocyte– ema. In: Braunwald E, Zipes DP, and Libby P (eds.) Heart
Disease: A Textbook of Cardiovascular Medicine, pp. 534–561.
macrophage colon stimulating factor (GM-CSF). The Philadelphia: Saunders.
value of reducing pulmonary microvascular pressure Guyton AC and Lindsey AW (1959) Effect of left atrial pressure
by fluid restriction and diuresis is also being inves- and decreased plasma protein concentration on the development
tigated in a randomized clinical trial. of pulmonary edema. Circulation Research 7: 649–657.
Matthay MA, Folkesson HG, and Clerici C (2002) Lung epithelial
fluid transport and the resolution of pulmonary edema. Phys-
See also: Acute Respiratory Distress Syndrome.
iological Reviews 82(3): 569–600.
High Altitude, Physiology and Diseases. Upper Matthay MA and Sakuma T (2001) Pulmonary edema: formation
Airway Obstruction. and reabsorption. In: Scharf SM, Pinsky MR, and Magder S
(eds.) Respiratory–Circulatory Interactions in Health and Dis-
ease, pp. 361–387. New York: Dekker.
Further Reading Sharma M and Teerlink JR (2004) A rational approach for the
Acute Respiratory Distress Syndrome Network (2000) Ventilation treatment of acute heart failure: current strategies and future
with lower tidal volumes as compared with traditional tidal vol- options. Current Opinion in Cardiology 19: 254–263.
umes for acute lung injury and the acute respiratory distress syn- Staub NC (1988) Lung liquid and protein exchange. Applied
drome. New England Journal of Medicine 342(18): 1302–1308. Cardiopulmonary Pathophysiology 2: 117–123.
Bernard GB, Artigas A, Brigham K, et al. (1994) The American– Taylor AE (1981) Capillary fluid filtration: starling forces and
European Consensus Conference on ARDS: definitions, mech- lymph flow. Circulation Research 49: 557–575.
anisms, relevant outcomes, and clinical trial coordination. Ware LB and Matthay MA (2000) The acute respiratory distress
American Journal of Respiratory and Critical Care Medicine syndrome. New England Journal of Medicine 342(18): 1334–
149: 818–824. 1349.
O P Sharma, University of Southern California School few or no symptoms; such is the case with pleural effusions
of Medicine, Los Angeles, CA, USA related to renal or hepatic failure. In others diseases, lung in-
volvement becomes a nuisance but is manageable; this occurs in
& 2006 Elsevier Ltd. All rights reserved.
gastroesophageal reflux disease and arteriovenous malforma-
tions in Osler–Rendau–Weber disease. On the other hand, in
Abstract certain diseases lung involvement progresses relentlessly, caus-
ing death or serious injury that influences the course of the
Pulmonary manifestations of systemic disorders are common. primary illness; such is the case in severe pneumonia in a di-
Almost all systemic diseases can involve the lung. In many ill- abetic patient or portopulmonary hypertension in chronic liver
nesses, lung complications remain relatively benign, producing failure.