Acute Respiratory Distress Syndrome

By: Yazmin RealivasquezStephen Huang

Jose Torres

What is ARDS?

ARDS is a respiratory condition characterized by hypoxemia, and stiff lungs, without mechanical ventilation most patients would die. ARDS represents a response to many different insults/injuries and evolves through different phases: alveolar capillary damage to lung resolution to a fibro-proliferative phase. The pulmonary epithelial and endothelial cellular damage is characterized by inflammation, apoptosis, necrosis and increased alveolar-capillary permeability, which lead to the development of alveolar edema.

Before 1992, the term ARDS was known as the adult respiratory distress syndrome. In 1994 The American-European Consensus Committee on ARDS standardized the definition and renamed it acute respiratory distress syndrome rather than adult because this can occur at any age. The term ALI (acute lung injury) was also introduced at that time.

Development of ARDS

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) describe syndromes of acute onset, bilateral, inflammatory pulmonary infiltrates and impaired oxygenation. The first known description of ARDS arrived with the invention of the stethoscope (Rene Theophile Hyacinthe Laennec)

Laennec: fatal “idiopathic pulmonary edema” Treatise on Diseases of the Chest (1821)

The wars of the twentieth century provided ample evidence that a great number of traumatic insults could result in edema related lung injury (“wet lung,” “shock lung,” “Da Nang lung”).

Ashbaugh et al: introduced the term “respiratory distress syndrome” to describe the constellation of acute onset tachypnea, hypoxemia, diffuse pulmonary infiltrates, and loss of lung compliance characterized by high short-term mortality in adultsAcute respiratory distress in adults (1967)

The terms ALI and ARDS finally achieved a consensus definition during the American–European Consensus Conference (AECC) on ARDS (1994)Allowed coordinated research efforts into the epidemiology, pathophysiology, and treatment of ALI/ARDS National Heart, Lung, and Blood Institute: ARDSNet

The difference between ALI and ARDS is the degree of hypoxemia, which you calculate using the ratio of arterial oxygen tension to fractional inspired oxygen concentration. Pa02/Fi02 normal ranges 300-500 mmHg, < 300 mmHg determines ALI, < 200 mmHg indicates ARDS.

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The pathology of ARDS can progress through three overlapping stages, exudative, proliferative, and fibrotic.

Exucdative Phase

Lung insults such as direct and indirect is what initiates the exucdative phase. This phase is the acute inflammatory stage of ARDS. It occurs by the release of pro-inflammatory cytokines

influx of neutrophils impaired endothelial cell barrier function decrease in surfactant production by

type II epithelial cells

Proliferative Phase

Second phase, the proliferative phase, develops 2–7 days after lung injury occurs. This phase is characterized by

decrease of type II pneumocytes early fibrotic changes thickening of the alveolar capillaries

In some patients, the proliferative phase progresses to a fibrotic stage.

Fibrotic Phase

The last phase, fibrotic stage is associated with

increased collagen deposition VQ mismatching decrease compliance ARDS results in multiple

pathophysiological changes causing severe respiratory dysfunction.

Many conditions can cause fluid to build up in the alveoli, preventing the lungs from filling with air and not moving enough oxygen into the bloodstream. As a result, the kidneys and the brain lack the oxygen they need. Without oxygen, the organs do not function well or at all.

Lung Injuries

Direct Pneumonia Breathing in smoke

and harmful irritants

Aspiration Ventilators Nearly drowning

Indirect Sepsis Blood transfusions Severe injury to the

chest and the head Severe bleeding

from an injury Pancreatitis Fat embolism Drug reactions

Signs and Symptoms

The first signs and symptoms is when the patient develops rapidly progressive dyspnea, tachypnea, and hypoxemia.

In some cases some people will be hypotensive, confused, and will have extreme tiredness.

Depending on the cause of ARDS early symptoms may occur before its development. Such as a cough, fever, SOB if the patient had PNA. Those who develop ARDS are often admitted to the hospital for other serious health problems.

Upon physical examination the patient may appear to be cyanotic, breath sounds will be heard as crackles. The doctor will ask for medical history or any other conditions relevant that would lead to non- cardiogenic pulmonary edema, to rule out CHF.

ARDS often has been differentiated from CHF, because both have similar signs of fluid overload.

Diagnosis

ARDS will be diagnosed if the patient’s PF Ratio < 300 mmHg would be considered mild ARDS (ALI), < 200 mmHg moderate ARDS, and < 100 mmHg severe ARDS.

Chest X-ray will show bilateral infiltrates not secondary to cardiogenic pulmonary edema.

Pulmonary Capillary wedge pressure (PCWP) < 18 mmHg

low central venous pressure (CVP) < 8 mmHg.

Initial test that can help with diagnosis, ABG ,blood tests, such as a CBC, blood chemistries, and blood culture, sputum culture, can help find the underlying cause.

Diagnostic Tests: The CXR (1)

The CXR may be “normal” for a period of time (hours – days) following the precipitating event (e.g. sepsis)

Full progression to diffuse, bilateral alveolar infiltrates takes place within 4-24 hrs. after the first abnormal radiographic signs appear

Shadows seen in lung parenchyma may be similar to those identified in CHF

Diagnostic Tests: The CXR (2)

› As alveolar filling continues, more of the lung parenchyma is involved - leading

at times to a near total

“white-out” of both fields CXR’s are strongly influenced by the effects of therapy

IV fluids can increase alveolar contentDiuretic agents may decrease total content

PEEP increases lung inflation thereby reducing regional lung density

Diagnostic Tests: The The CXR (3)

Computed Tomography (1)

Despite what appears to be a UNIVERSAL improvement of all lung fields on standard CXR, C.T. will often reveal patchy areas of infiltrate interspersed with normal-appearing lung!

Degree of lung involvement on C.T. correlates with the efficiency of gas exchange and underlying lung compliance

With appropriate precautions & continuous monitoring, clinically-indicated tomography can and should be undertaken in all but the most unstable ARDS patients

Computed Tomography (2)

CT can also reveal Barotrauma or localized infection i.e. loculated empyema or abscess

Gas Exchange: the ABG’s

Initial: Respiratory Alkalosis w/Hypoxemia› The hypoxemia is resistant to supplemental oxygen

As fluid accumulation progresses, the hypoxemia worsens

› leads, eventually, to the point of ventilatory support The efficiency of gas exchange [PaO2/FiO2] at the onset of

ARDS, has correlated to patient outcome

Dead space ventilation is markedly increased in patient with ARDS

this translates into a high rate of minute ventilation [RR x Vt] to maintain effective CO2 eliminationREMEMER: Use Arterial Line placement for frequent ABG draw, monitor hemodynamics/blood pressure

if the problem in this disease is integrity of the alveolar capillary membrane –

Then how do we measure it’s barrier function?

“Measuring” Membrane Integrity (1)

Analyze the Protein Content within the Alveolus OrMeasure the flux of radiolabeled proteins

When this is done, the pulmonary edema that we see in ARDS appears to be noncardiogenic in etiology!

“Measuring” Membrane Integrity (2)

The amount of extravascular water within the lungs can also be measured:› Thermal Indocyanine Green Technique› Rare to see in clinical setting

How much fluid do we normally have in our lungs?

“Measuring” Membrane Integrity (3)

Upper limit of normal: 500 cc’s

The “average” ARDS patient: 1500 cc’s

Can be as much as 6-8x the normal! (4 liters of fluid)

Broncho-alveolar Lavage (BAL)

Usually employed to document nosocomial infection› can be safely performed in ARDS patients› has never been prospectively validated› can identify opportunistic lung infections presenting as

ARDS 2 findings in ARDS: [nonspecific]

› Increased # of PMN’s (nearly 80% of total cell population) “polymorphonuclear neutrophils” (has ROS properties)

› EosinophiliaThese patients may respond to corticosteroids

Complications

Patients with ARDS are more prone to developing other medical problems while hospitalized. Being in the hospital and lying down for a long period of time or on a ventilator can put you at high risk for infections, such as pneumonia VAP, HAP.

The patient can develop a pneumothorax from the vent, atelectasis. ARDS causes the lungs to be stiff, which makes it hard for the lungs to expand and fill with air. Being on the vent for a long period of time can also cause scarring of the lungs.

The developments of blood clots are common because the patient is lying down for long periods. A deep vein thrombosis can develop and it can travel through the blood stream, into the lungs, blocking blood flow and causing a pulmonary embolism. Treat it with fibrolytics.

According to AARON SAGUIL, MD “A large, prospective European trial estimated that most cases of acute respiratory distress syndrome are associated with pneumonia or sepsis. It is estimated that 7.1 percent of all patients admitted to an intensive care unit and 16.1 percent of all patients on mechanical ventilation develop ALI or ARDS. In-hospital mortality related to these conditions is between 34% and 55%, and most deaths are due to multi organ failure.”

https://www.youtube.com/watch?v=aXjaxvL6y7I

Neonates & RDS

Respiratory distress syndrome (RDS) is a breathing disorder that affects newborns, and rarely occurs in full term babies. The condition is more common in premature infants born about 6 weeks or more before their due dates.

Premature babies are more prone to developing RDS because their lungs are unable to make enough surfactant. Surfactant is a liquid that coats the inside of the lungs. It helps keeps the alveoli patent so that they can breathe in air once they're born.

The lack of surfactant, will cause the lungs to collapse and the infant has to increase their WOB.

Just like adults they are unable to get enough oxygen in for proper gas exchange and the body’s organs get damaged, if immediate treatment is not given.

Most babies who are affected with RDS show signs of breathing problems and a lack of oxygen at birth or within the first few hours after. Initially prematures will develop RDS within 24 hours.

https://www.youtube.com/watch?v=NBA9iigiDgk&index=1&list=PL7EA9354BC2DD8B67

Research has shown that it is not possible to measure Lung Injury

…What can we do at the bedside?

Hemodynamics: Cardiac Output

CO = HR X SV

“the amount of blood pumped by the heart per unit time”

Normal C.O. = 3.5 – 8.5 L/min Preload Afterload Contractil

ity

Compliance Heart Rate

The Hemodynamic Parameters (1)

there is not a diagnostic hemodynamic parameter for ARDS

Characteristic Features of ARDS› Pulmonary edema› High Cardiac Output› Low Pulmonary Wedge Pressure (PWP)

The Hemodynamic Parameters (2)

There are conditions that mimic the “ARDS features”› Partially-treated Volume Overload› “Flash Pulmonary Edema” (i.e. acute

myocardial infartion)Both of these cause a transient elevation in the filling pressures as well as alveolar congestion

Hemodynamics can also be elevated with:› Increased Intrathoracic Pressure (artifactual)› Fluid Administration for Hypotension

(therapeutic)

The Hemodynamic Parameters (3)

Cardiac Function can also be depressed:› Acidosis› Hypoxia› Sepsis-related Depressant PhenomenonThis creates a confusing hemodynamic combination in the setting of developing lung injury

The Hemodynamic Parameters (4)

Invasive cardiac monitoring can play a direct role in management of ARDS during the early phase to “rule out” Cardiogenic Edema& during subsequent management - to optimize fluid balance while efficiently maximizing cardiac performance

Treatment: General Principles

Currently, specific measures to correct abnormality in vascular permeability or to limit the degree of inflammatory reaction present in ARDS do not exist.

EARLY antibiotic therapy and infection prevention is critical › Remove intravascular lines, drain infected fluid collections, removal of

infections sites› Pay attention to skin infections, IV line infections, pneumothorax, DVT› Prevent VAP (e.g. use of inline suction devices, elevation of head of bed)

Prone position (face down) may improve oxygenation by relieving atelectasis and improving perfusion. 70-80% improvement vs. Supine

Permissive hypercapnia to prevent VILI What cellular functions are we trying to maintain?

› Alveolar Gas Exchange / Organ Perfusion /Aerobic MetabolismMOST TREATMENTS ARE CONTROVERSIAL! (e.g. inhaled NO, corticosteroids)

Ventilator Strategies

APRV (Airway Pressure Release Ventilation)› Two levels of CPAP with intermittent release phase (24

hours recruitment!)Inverse ratio ventilation (short E-time) helps Maintain alveolar inflation › Improves MAP/oxygenation by stabilizing collapsed

alveoli› DOES NOT INCREASE PIP› Potentially decreases deadspace?› Increases organ/tissue perfusion and increases urine

output 2/2 increased kidney perfusion› Promotes unrestricted spontaneous breathing -> less

sedation/paralytics -> less vasopressor support

Goal: control/minimize lung damage “protect”

Initial Settings

If going from conventional ventilation: Evaluate the PPL, MAP, and VE

PHigh: Look to the PPL (with a limit of 35 cmH2O) Alternative: look at MAP and add a few

PLow: zero or very low level (2-3 cmH2O) TLow: 0.6 to 1.0 sec.

NO spontaneous efforts THigh or f: A THigh of about 5 sec or a RR of about 10 bpm with

a fixed TLow is a good starting point

MAP on APRV is calculated by: (Phigh x Thigh) + (Plow + Tlow) / Thigh

What about Hemodynamics?

Improved right- and left- heart filling and preload› Improved CO› Improved Oxygen Delivery that

matches/exceeds demands› Improved perfusion to splanchnic organs,

renal, and cerebral arteries

Why Spontaneous Breathing?

Improved distribution leads to reduced amounts of shunted blood and improved V/Q relationship. In spontaneous breathing, there is more volume distribution to gravity dependent regions (Slutsky & Brochard, 2005). In CMV, more volume moves into non-dependent regions (collapsed) = increased dead space (Vd/Vt) regions = poor perfusion

Incidence (annual) of Acute respiratory distress syndrome:150,000 Americans will be diagnosed with acute respiratory distress syndrome each year

Incidence extrapolations for the United States of America for Acute respiratory distress syndrome:150,000 per year12,500 per month2,884 per week410 per day17 per hour

National Heart Lung and Blood Institute

ARDS presents within 12-24 hours of antecedent event ARDS patients intubated within 72 hours in 90% cases High mortality rate (ICU: 37%, overall: 42%) Predictors of better prognosis - Those who survive acute respiratory distress syndrome in the first 2 weeks have better prognosis - Age under 55 years - Trauma related to acute respiratory distress syndrome Predictors of poor prognosis - Elderly (especially over age 70 years) - Immunocompromised patients - Chronic Liver Disease - Increased dead space fraction Only 34% of ards survivors are well enough to be

discharged directly home ALI/ARDS leads to approximately 2.2 million days in the

ICU

Country/Region Extrapolated Incidence Population Estimated Used USA 161,942 293,655,405 Canada 17,927 32,507,874 United Kingdom 33,237 60,270,708 France 33,322 60,424,213 Greece 5,871 10,647,529 Germany 45,454 82,424,609 Ireland 2,189 3,969,558 Italy 32,016 58,057,477 Netherlands 8,999 16,318,199 Poland 21,301 38,626,349 Spain 22,213 40,280,780 China 716,276 1,298,847,624 India 587,355 1,065,070,607 Japan 70,220 127,270,708 Philippines 47,559 86,241,697 Bangladesh 77,945 141,340,476 Thailand 35,771 64,865,523 Russia 79,397 143,974,059 Australia 10,981 19,913,144 New Zealand 2,202 3,993,817 Afghanistan 15,725 28,513,677 Egypt 41,976  76,117,421 Israel 3,418 6,199,008 Saudi Arabia 14,225 25,795,938 Turkey   37,992 68,893,918 Mexico 57,882 104,959,594 Brazil 101,526 184,101,109 Puerto Rico 3,418 6,199,008 South Africa 24,512 44,448,470 

Population estimates based upon  US Census Bureau, Population Estimates, 2004 and  US Census Bureau, International Data Base, 2004

ARDS is associated with a hospital mortality of approximately 40%. Mortality varies according to severity of oxygenation deficit.

In the Berlin definition clinical study cohort, mortality was 27% (95% confidence interval [CI] 24%–30%) in patients with mild ARDS (PaO2/FIO2 201–300), 32% (95% CI 29%–34%) in those with moderate ARDS (PaO2/ FIO2 101–200), and 45% (95% CI 42%–48%) in patients with severe ARDS.

Although worsening oxygenation is a risk factor for ARDS mortality, patients generally die from multisystem organ failure or progressive underlying illness; only a minority of ARDS patients (13%–19%) die from refractory respiratory failure.

Although mortality has declined since two decades ago, initial progress in reducing ARDS mortality is likely due:

- increased implementation of a low tidal–volume mechanical ventilation strategy that reduces: + further lung injury + systemic inflammation + subsequent multisystem organ failure However, among patients who receive low tidal–volume ventilation, mortality rates

remain unchanged. Thus, additional treatments for ARDS are sorely needed.

Mortality

• Because of the high mortality and substantial variability in outcomes in patients with ARDS, identification of risk factors for mortality are important to determine prognosis and guide clinical decision-making. In line with observations that mortality in ARDS is generally due to multiple-organ system failure.

• The best-performing determinants of prognosis in ARDS: - Age - Severity of disease (APACHE scores) - Predisposing conditions *Ex, trauma-induced ARDS has a much more favorable prognosis (approximately 10% mortality) than other conditions • Clinical risk factors for ARDS mortality include poor oxygenation

and poor lung compliance, *Berlin ARDS Definition Task Force did not find that lung compliance added significant predictive value over oxygenation alone. • Other predictors of ARDS mortality: - Pulmonary vascular dysfunction - Lack of temporal improvement in dead-space fraction - Lung compliance - Oxygenation - Shock.

Until the 1990s, most studies reported a 40-70% mortality rate for ARDS. However, 2 reports in the 1990s, one from a large county hospital in Seattle and one from the United Kingdom, suggested much lower mortality rates, in the range of 30-40%. Possible explanations for the improved survival rates may be better understanding and treatment of sepsis, recent changes in the application of mechanical ventilation, and better overall supportive care of critically ill patients.

Note that most deaths in ARDS patients are attributable to sepsis (a poor prognostic factor) or multi-organ failure rather than to a primary pulmonary cause, although the recent success of mechanical ventilation using smaller tidal volumes may suggest a role of lung injury as a direct cause of death.

Mortality in ARDS increases with advancing age. The study performed in King County, Washington, found mortality rates of 24% in patients between ages 15 and 19 years and 60% in patients aged 85 years and older. The adverse effect of age may be related to underlying health status.

Morbidity is considerable. Patients with ARDS are likely to have prolonged hospital courses, and they frequently develop nosocomial infections, especially ventilator-associated pneumonia (VAP). In addition, patients often have significant weight loss and muscle weakness, and functional impairment may persist for months after hospital discharge.

Severe disease and prolonged duration of mechanical ventilation are predictors of persistent abnormalities in pulmonary function. Survivors of ARDS have significant functional impairment for years following recovery.

Indices of oxygenation and ventilation, including the PaO2/FIO2 ratio, do not predict the outcome or risk of death. The severity of hypoxemia at the time of diagnosis does not correlate well with survival rates. However, the failure of pulmonary function to improve in the first week of treatment is a poor prognostic factor.

Peripheral blood levels of decoy receptor 3 (DcR3), a soluble protein with immunomodulatory effects, independently predict 28-day mortality in ARDS patients. In a study comparing DcR3, soluble triggering receptor expressed on myeloid cells (sTREM)-1, TNF-alpha, and IL-6 in ARDS patients, plasma DcR3 levels were the only biomarker to distinguish survivors from nonsurvivors at all time points in week 1 of ARDS. Non survivors had higher DcR3 levels than survivors, regardless of APACHE II scores, and mortality was higher in patients with higher DcR3 levels.

An evidence-based approach to the management of acute lung injury and acute respiratory distress syndrome [A] If urine output

> 0.5 mL/kg/hr and mean arterial pressure > 60 mmHg with no vasopressor support. [B] Consider use

of ARDSNet.org positive end expiratory pressure (PEEP) table to titrate to PEEP upwards until plateau pressure reaches 30 mmHg, or use stress index to titrate PEEP.

[C] May require transfer to tertiary care facility.

The End

Work Cited

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