A R D SA R D S

Adult Respiratory distress Syndrome Adult Respiratory distress Syndrome (ARDS)(ARDS)

Variety of unrelated massive insults injure gas Variety of unrelated massive insults injure gas exchanging surface of Lungsexchanging surface of Lungs

First described as clinical syndrome in 1967 by First described as clinical syndrome in 1967 by Ashbaugh & Petty Ashbaugh & Petty

Clinical terms synonymous with ARDS Clinical terms synonymous with ARDS Acute respiratory failure Acute respiratory failure

Capillary leak syndrome Capillary leak syndrome Da Nang Lung Da Nang Lung Shock Lung Shock Lung Traumatic Traumatic wet Lung wet Lung Adult hyaline membrane diseaseAdult hyaline membrane disease

欧美欧美 ARDSARDS 联席会议联席会议

Report of European-American Consensus Report of European-American Consensus Conference on ARDS: Definitions, Conference on ARDS: Definitions, Mechanism, Relevant Outcomes and Mechanism, Relevant Outcomes and Clinical Trial Coordination (1992)Clinical Trial Coordination (1992)

From Am J Respir Crit Care Med, 1994,149:818From Am J Respir Crit Care Med, 1994,149:818

New and ImprovedNew and Improved

AdultAdult Respiratory Distress Syndrome Respiratory Distress Syndrome

AcuteAcute Respiratory Distress Syndrome Respiratory Distress Syndrome

Introduction Introduction

Acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a clinical syndrome of severe (ARDS) is a clinical syndrome of severe dyspnea of rapid onset, hypoxemia, and dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to diffuse pulmonary infiltrates leading to respiratory failure. ARDS is caused by respiratory failure. ARDS is caused by diffuse lung injury from many underlying diffuse lung injury from many underlying medical and surgical disorders medical and surgical disorders

Risk Factors in ARDSRisk Factors in ARDS

Sepsis 3.8% Sepsis 3.8% Cardiopulmonary bypass 1.7% Cardiopulmonary bypass 1.7% Transfusion 5.0% Transfusion 5.0% Severe pneumonia 12.0% Severe pneumonia 12.0% Burn 2.3% Burn 2.3% Aspiration 35.6% Aspiration 35.6% Fracture 5.3% Fracture 5.3% Intravascular coagulopathy 12.5% Intravascular coagulopathy 12.5% Two or more of the above 24.6% Two or more of the above 24.6%

Clinical Disorders Associated with ARDSClinical Disorders Associated with ARDS

Direct Lung Injury Indirect Lung Injury

Common causes Common Causes

Pneumonia SepsisAspiration of gastriccontents

Severe trauma with shock ,multiple transfusions

Less common causes Less common causes

Pulmonary contusion Cardiopulmonary bypassFat emboli Drug overdoseNear-Drowning Acute pancreatitisI nhalational injury Transfusions of blood productsReperfusion pulmonaryedema

Acute lung injury (ALI) is a less severe Acute lung injury (ALI) is a less severe disorder but has the potential to evolve into disorder but has the potential to evolve into ARDS The arterial (a) PO2 (in ARDS The arterial (a) PO2 (in mmHg)/FIO2 (inspiratory O2 fraction) mmHg)/FIO2 (inspiratory O2 fraction) <200 mmHg is characteristic of ARDS, <200 mmHg is characteristic of ARDS, while a PaO2/FIO2 between 200 and 300 while a PaO2/FIO2 between 200 and 300 identifies patients with ALI who are likely identifies patients with ALI who are likely to benefit from aggressive therapy. to benefit from aggressive therapy.

Diagnostic Criteria for ALI and ARDS

Oxygenation Onset Chest Radiograph Absence of Left Atrial

Hypertension

ALI:

PaO2 /FIO2

<=300mmHg

Acute Bilateral alveolar

Or interstitial

infiltrates

PCWP <= 18 mmHg or no clinical evidence of

increased left

Atrial pressure

ARDS:

PaO 2 /FIO 2

<=200mmHg

The annual incidences of ALI and ARDS The annual incidences of ALI and ARDS are estimated to be up to 80/100,000 and are estimated to be up to 80/100,000 and 60/100,000, respectively. Approximately 60/100,000, respectively. Approximately 10% of all intensive care unit (ICU) 10% of all intensive care unit (ICU) admissions suffer from acute respiratory admissions suffer from acute respiratory failure, with ~20% of these patients meeting failure, with ~20% of these patients meeting criteria for ALI or ARDS.criteria for ALI or ARDS.

EtiologyEtiology

most cases (>80%) are caused by a relatively most cases (>80%) are caused by a relatively small number of clinical disorders, namely, severe small number of clinical disorders, namely, severe sepsis syndrome and/or bacterial pneumonia sepsis syndrome and/or bacterial pneumonia (~40–50%), trauma, multiple transfusions, (~40–50%), trauma, multiple transfusions, aspiration of gastric contents, and drug overdose aspiration of gastric contents, and drug overdose

The risks of developing ARDS are increased in The risks of developing ARDS are increased in patients suffering from more than one patients suffering from more than one predisposing medical or surgical condition; predisposing medical or surgical condition;

Several other clinical variables have been Several other clinical variables have been associated with the development of ARDS associated with the development of ARDS

older age, older age, chronic alcohol abuse, chronic alcohol abuse, metabolic acidosis, metabolic acidosis, severity of critical illness. severity of critical illness.

Clinical Course and Pathophysiology Clinical Course and Pathophysiology

The natural history of ARDS is marked by The natural history of ARDS is marked by three phasesthree phases

——exudative, proliferative, and fibroticexudative, proliferative, and fibrotic ——each with characteristic clinical and each with characteristic clinical and

pathologic features pathologic features

Exudative Proliferative Fibrotic

Hyaline Interstitial Inflammation Edema Membranes Interstitial Fibrosis Fibrosis

Day: 0 2 7 14 21. . .

Exudative PhaseExudative Phase

Endothelial injury: increased Endothelial injury: increased permeability of alveolar - capillary permeability of alveolar - capillary barrierbarrier

Pro-inflammatory mechanismsPro-inflammatory mechanisms Collapse of large sections of dependent lung Collapse of large sections of dependent lung

markedly decreases lung compliance. markedly decreases lung compliance.

Consequently, intrapulmonary shunting and Consequently, intrapulmonary shunting and hypoxemia develop and the work of hypoxemia develop and the work of breathing rises, leading to dyspnea. The breathing rises, leading to dyspnea. The pathophysiologic alterations in alveolar pathophysiologic alterations in alveolar spaces are exacerbated by microvascular spaces are exacerbated by microvascular occlusion, which leads to reductions in occlusion, which leads to reductions in pulmonary arterial blood flow to ventilated pulmonary arterial blood flow to ventilated portions of the lung, increasing the dead portions of the lung, increasing the dead space, and pulmonary hypertension. Thus, in space, and pulmonary hypertension. Thus, in addition to severe hypoxemia, hypercapnia addition to severe hypoxemia, hypercapnia secondary to an increase in pulmonary dead secondary to an increase in pulmonary dead space is also prominent in early ARDS. space is also prominent in early ARDS.

The exudative phase encompasses the first 7 The exudative phase encompasses the first 7 days of illness after exposure to a precipitating days of illness after exposure to a precipitating ARDS risk factor ARDS risk factor

Dyspnea develops with a sensation of rapid Dyspnea develops with a sensation of rapid shallow breathing and an inability to get shallow breathing and an inability to get enough air. enough air.

Tachypnea and increased work of breathing Tachypnea and increased work of breathing frequently result in respiratory fatigue and frequently result in respiratory fatigue and ultimately in respiratory failure. ultimately in respiratory failure.

Laboratory values are generally nonspecific Laboratory values are generally nonspecific and primarily indicative of underlying and primarily indicative of underlying clinical disorders.clinical disorders.

The chest radiograph usually reveals The chest radiograph usually reveals alveolar and interstitial opacities involving alveolar and interstitial opacities involving at least three-quarters of the lung fields at least three-quarters of the lung fields

Chest computed tomography (CT) scanning Chest computed tomography (CT) scanning in ARDS reveals extensive heterogeneity of in ARDS reveals extensive heterogeneity of lung involvement lung involvement

ARDS:CT Scan ViewARDS:CT Scan View

Proliferative Phase Proliferative Phase

Most patients recover rapidly and are liberated from Most patients recover rapidly and are liberated from mechanical ventilation during this phase mechanical ventilation during this phase

Some patients develop progressive lung injury and Some patients develop progressive lung injury and early changes of pulmonary fibrosis during the early changes of pulmonary fibrosis during the proliferative phase proliferative phase

the initiation of lung repair, organization of alveolar the initiation of lung repair, organization of alveolar exudates, and a shift from a neutrophil to a exudates, and a shift from a neutrophil to a lymphocyte-predominant pulmonary infiltrate lymphocyte-predominant pulmonary infiltrate

type II pneumocytes synthesize new type II pneumocytes synthesize new pulmonary surfactant and differentiate into pulmonary surfactant and differentiate into type I pneumocytes type I pneumocytes

The presence of alveolar type III The presence of alveolar type III procollagen peptide, a marker of pulmonary procollagen peptide, a marker of pulmonary fibrosis, is associated with a protracted fibrosis, is associated with a protracted clinical course and increased mortality from clinical course and increased mortality from ARDS ARDS

Fibrotic Phase Fibrotic Phase

many patients with ARDS recover lung function many patients with ARDS recover lung function 3–4 weeks after the initial pulmonary injury, some 3–4 weeks after the initial pulmonary injury, some will enter a fibrotic phase that may require long-will enter a fibrotic phase that may require long-term support on mechanical ventilators and/or term support on mechanical ventilators and/or supplemental oxygen. supplemental oxygen.

the alveolar edema and inflammatory exudates of the alveolar edema and inflammatory exudates of earlier phases are now converted to extensive earlier phases are now converted to extensive alveolar duct and interstitial fibrosis alveolar duct and interstitial fibrosis

ARDS : Diminished Surfactant ActivityARDS : Diminished Surfactant Activity

Surfactant product of Type II pneumocytesSurfactant product of Type II pneumocytes Importance of surfactant:Importance of surfactant:

– P = 2T/r (Laplace equation; P: trans-P = 2T/r (Laplace equation; P: trans-pulmonary pressure, T: surface tension, r: pulmonary pressure, T: surface tension, r: radius)radius)

Surfactant proportions surface tension to Surfactant proportions surface tension to surface area: thussurface area: thus

Acinar architecture is markedly disrupted, Acinar architecture is markedly disrupted, leading to emphysema-like changes with leading to emphysema-like changes with large bullae. large bullae.

Intimal fibroproliferation in the pulmonary Intimal fibroproliferation in the pulmonary microcirculation leads to progressive microcirculation leads to progressive vascular occlusion and pulmonary vascular occlusion and pulmonary hypertension. hypertension.

The physiologic consequences include an The physiologic consequences include an increased risk of increased risk of

pneumothorax, pneumothorax, reductions in lung compliance, reductions in lung compliance, increased pulmonary dead space. increased pulmonary dead space.

Acute Respiratory Distress: TreatmentAcute Respiratory Distress: Treatment

General Principles :General Principles : (1) the recognition and treatment of the underlying (1) the recognition and treatment of the underlying

medical and surgical disorders (e.g., sepsis, medical and surgical disorders (e.g., sepsis, aspiration, trauma); aspiration, trauma);

(2) minimizing procedures and their complications(2) minimizing procedures and their complications (3) prophylaxis against venous (3) prophylaxis against venous

thromboembolism, gastrointestinal bleeding, and thromboembolism, gastrointestinal bleeding, and central venous catheter infections; central venous catheter infections;

(4) the prompt recognition of nosocomial (4) the prompt recognition of nosocomial infections; and infections; and

(5) provision of adequate nutrition (5) provision of adequate nutrition

MANAGEMENT OF ARDSMANAGEMENT OF ARDS

Mechanical ventilation Mechanical ventilation corrects hypoxemia/respiratory acidosiscorrects hypoxemia/respiratory acidosis

Fluid management Fluid management correction of anemia and hypovolemiacorrection of anemia and hypovolemia

Pharmacological intervention Pharmacological intervention Dopamine to augment C.O. Dopamine to augment C.O.

Diuretics Diuretics Antibiotics Antibiotics Corticosteroids - no Corticosteroids - no demonstrated benefit demonstrated benefit early disease, early disease, helpful 1 week laterhelpful 1 week later

Mortality continues to be 50 to 60%Mortality continues to be 50 to 60%

Management of Mechanical Management of Mechanical Ventilation Ventilation

Patients meeting clinical criteria for ARDS Patients meeting clinical criteria for ARDS frequently fatigue from increased work of frequently fatigue from increased work of breathing and progressive hypoxemia, breathing and progressive hypoxemia, requiring mechanical ventilation for support requiring mechanical ventilation for support

Ventilator-Induced Lung Injury Ventilator-Induced Lung Injury Ventilator-induced injury can be demonstrated in Ventilator-induced injury can be demonstrated in

experimental models of ALI, with high tidal experimental models of ALI, with high tidal volume ventilation resulting in additional, volume ventilation resulting in additional, synergistic alveolar damage. These findings led to synergistic alveolar damage. These findings led to the hypothesis that ventilating patients suffering the hypothesis that ventilating patients suffering from ALI or ARDS with lower tidal volumes from ALI or ARDS with lower tidal volumes would protect against ventilator-induced lung would protect against ventilator-induced lung injury and improve clinical outcomes. injury and improve clinical outcomes.

compared low tidal volume (6 mL/kg compared low tidal volume (6 mL/kg predicted body weight) ventilation to predicted body weight) ventilation to conventional tidal volume (12 mL/kg conventional tidal volume (12 mL/kg predicted body weight) ventilation. predicted body weight) ventilation.

Mortality was significantly lower in the low Mortality was significantly lower in the low tidal volume patients (31%) compared to the tidal volume patients (31%) compared to the conventional tidal volume patients (40%). conventional tidal volume patients (40%).

This improvement in survival represents the This improvement in survival represents the most substantial benefit in ARDS mortality most substantial benefit in ARDS mortality demonstrated for demonstrated for anyany therapeutic therapeutic intervention in ARDS to date. intervention in ARDS to date.

Prevention of Alveolar CollapsePrevention of Alveolar Collapse In ARDS, the presence of alveolar and In ARDS, the presence of alveolar and

interstitial fluid and the loss of surfactant interstitial fluid and the loss of surfactant can lead to a marked reduction of lung can lead to a marked reduction of lung compliance. compliance.

Without an increase in end-expiratory Without an increase in end-expiratory pressure, significant alveolar collapse can pressure, significant alveolar collapse can occur at end-expiration, impairing occur at end-expiration, impairing oxygenation oxygenation

In most clinical settings, positive end-In most clinical settings, positive end-expiratory pressure (PEEP) is empirically expiratory pressure (PEEP) is empirically set to minimize FIO2 and maximize PaO2.set to minimize FIO2 and maximize PaO2.

On most modern mechanical ventilators, it On most modern mechanical ventilators, it is possible to construct a static pressure–is possible to construct a static pressure–volume curve for the respiratory system. volume curve for the respiratory system.

Oxygenation can also be improved by Oxygenation can also be improved by increasing mean airway pressure with increasing mean airway pressure with "inverse ratio ventilation." "inverse ratio ventilation."

In several randomized trials, mechanical In several randomized trials, mechanical ventilation in the prone position improved ventilation in the prone position improved arterial oxygenation, but its effect on arterial oxygenation, but its effect on survival and other important clinical survival and other important clinical outcomes remains uncertain. outcomes remains uncertain.

Other Strategies in Mechanical VentilationOther Strategies in Mechanical Ventilation

These include high-frequency ventilation (HFV), These include high-frequency ventilation (HFV), i.e., ventilating at extremely high respiratory rates i.e., ventilating at extremely high respiratory rates (5–20 cycles per second) and low tidal volumes (5–20 cycles per second) and low tidal volumes (1–2 mL/kg). Also, lung-replacement therapy with (1–2 mL/kg). Also, lung-replacement therapy with extracorporeal membrane oxygenation (ECMO extracorporeal membrane oxygenation (ECMO

Data in support of the efficacy of "adjunctive" Data in support of the efficacy of "adjunctive" ventilator therapies (e.g., high PEEP, inverse ratio ventilator therapies (e.g., high PEEP, inverse ratio ventilation, prone positioning, HFV, ECMO, and ventilation, prone positioning, HFV, ECMO, and PLV) remain incomplete, so these modalities are PLV) remain incomplete, so these modalities are not routinely used. not routinely used.

Fluid Management Fluid Management

Increased pulmonary vascular permeability Increased pulmonary vascular permeability leading to interstitial and alveolar edema leading to interstitial and alveolar edema rich in protein is a central feature of ARDS. rich in protein is a central feature of ARDS.

impaired vascular integrity augments the impaired vascular integrity augments the normal increase in extravascular lung water normal increase in extravascular lung water that occurs with increasing left atrial that occurs with increasing left atrial pressure pressure

aggressive attempts to reduce left atrial aggressive attempts to reduce left atrial filling pressures with fluid restriction and filling pressures with fluid restriction and diuretics should be an important aspect of diuretics should be an important aspect of ARDS management, limited only by ARDS management, limited only by hypotension and hypoperfusion of critical hypotension and hypoperfusion of critical organs, such as the kidneys. organs, such as the kidneys.

GlucocorticoidsGlucocorticoids

Inflammatory mediators and leukocytes are Inflammatory mediators and leukocytes are abundant in the lungs of patients with abundant in the lungs of patients with ARDS. ARDS.

Many attempts have been made to treat both Many attempts have been made to treat both early and late ARDS with glucocorticoids to early and late ARDS with glucocorticoids to reduce this potentially deleterious reduce this potentially deleterious pulmonary inflammation.pulmonary inflammation.

Few studies have shown any benefit. Few studies have shown any benefit.

Current evidence does Current evidence does notnot support the use support the use of glucocorticoids in the care of ARDS of glucocorticoids in the care of ARDS patients. patients.

However, the ARDS Network is currently However, the ARDS Network is currently conducting a large-scale study of conducting a large-scale study of glucocorticoids in the late phase of ARDS glucocorticoids in the late phase of ARDS

Other Therapies Other Therapies

Clinical trials of surfactant replacement therapy Clinical trials of surfactant replacement therapy have proved disappointing. Similarly, although have proved disappointing. Similarly, although several randomized clinical trials of inhaled nitric several randomized clinical trials of inhaled nitric oxide (NO) in ARDS have demonstrated improved oxide (NO) in ARDS have demonstrated improved oxygenation, no significant improvement in oxygenation, no significant improvement in survival or decrements in time on mechanical survival or decrements in time on mechanical ventilation has been observed. Therefore, the use ventilation has been observed. Therefore, the use of NO is of NO is notnot currently recommended in ARDS. currently recommended in ARDS.

Recommendations Recommendations

Many clinical trials have been undertaken to Many clinical trials have been undertaken to improve the outcome of patients with ARDS; most improve the outcome of patients with ARDS; most have been unsuccessful in modifying the natural have been unsuccessful in modifying the natural history. The large number and uncertain clinical history. The large number and uncertain clinical efficacy of ARDS therapies can make it difficult efficacy of ARDS therapies can make it difficult for clinicians to select a rational treatment plan, for clinicians to select a rational treatment plan, and these patients' critical illness can tempt and these patients' critical illness can tempt physicians to try unproven and potentially harmful physicians to try unproven and potentially harmful therapies therapies

Treatment Recommendationa 

Mechanical ventilation:  

  Low tidal volume A

  High-PEEP or "open-lung" C

  Prone position C

  Recruitment maneuvers C

  High-frequency ventilation and ECMO D

Minimize left atrial filling pressures B

Glucocorticoids C

Surfactant replacement, inhaled nitric oxide, and other antiinflammatory therapy (e.g., ketoconazole, PGE1, NSAIDs)

 

D

PrognosisPrognosis

Mortality Mortality Functional Recovery in ARDS Survivors Functional Recovery in ARDS Survivors

MortalityMortality

Recent mortality estimates for ARDS range Recent mortality estimates for ARDS range from 41 to 65%. There is substantial from 41 to 65%. There is substantial variability, but a trend toward improved variability, but a trend toward improved ARDS outcomes appears evident. ARDS outcomes appears evident.

improvement in survival is likely secondary improvement in survival is likely secondary to advances in the care of septic/infected to advances in the care of septic/infected patients and those with multiple organ patients and those with multiple organ failure failure

Several risk factors for mortality to help Several risk factors for mortality to help estimate prognosis have been identified. estimate prognosis have been identified.

Advanced age is an important risk factor Advanced age is an important risk factor Preexisting organ dysfunction from chronic Preexisting organ dysfunction from chronic

medical illness is an important additional medical illness is an important additional risk factor for increased mortality. risk factor for increased mortality.

Several factors related to the presenting Several factors related to the presenting clinical disorders also increase risk for clinical disorders also increase risk for ARDS mortality. ARDS mortality.

Surprisingly, there is little value in predicting Surprisingly, there is little value in predicting ARDS mortality from the extent of hypoxemia ARDS mortality from the extent of hypoxemia and any of the following measures of the severity and any of the following measures of the severity of lung injury: the level of PEEP used in of lung injury: the level of PEEP used in mechanical ventilation, the respiratory mechanical ventilation, the respiratory compliance, the extent of alveolar infiltrates on compliance, the extent of alveolar infiltrates on chest radiography, and the lung injury score (a chest radiography, and the lung injury score (a composite of all these variables). However, recent composite of all these variables). However, recent data indicate that an early (within 24 h of data indicate that an early (within 24 h of presentation) elevation in dead space may predict presentation) elevation in dead space may predict increased mortality from ARDS increased mortality from ARDS

Functional Recovery in ARDS Survivors Functional Recovery in ARDS Survivors

it is a testament to the resolving powers of the it is a testament to the resolving powers of the lung that the majority of patients recover nearly lung that the majority of patients recover nearly normal lung function. normal lung function.

Patients usually recover their maximum lung Patients usually recover their maximum lung function within 6 months. One year after function within 6 months. One year after endotracheal extubation, over a third of ARDS endotracheal extubation, over a third of ARDS survivors have normal spirometry values and survivors have normal spirometry values and diffusion capacity. Most of the remaining patients diffusion capacity. Most of the remaining patients have only mild abnormalities in their pulmonary have only mild abnormalities in their pulmonary function function

recovery of lung function is strongly recovery of lung function is strongly associated with the extent of lung injury in associated with the extent of lung injury in early ARDS. Low static respiratory early ARDS. Low static respiratory compliance, high levels of required PEEP, compliance, high levels of required PEEP, longer durations of mechanical ventilation, longer durations of mechanical ventilation, and high lung injury scores are all and high lung injury scores are all associated with worse recovery of associated with worse recovery of pulmonary function. pulmonary function.

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