Acute respiratory distress syndrome
Encyclopedia
Acute respiratory distress syndrome (ARDS), also known as respiratory distress syndrome (RDS) or adult respiratory distress syndrome (in contrast with IRDS
Infant respiratory distress syndrome
Infant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome in premature infants caused by developmental insufficiency of surfactant production and structural...

) is a serious reaction to various forms of injuries to the lung
Human lung
The human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...

.

ARDS is a severe lung
Human lung
The human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...

 disease caused by a variety of direct and indirect issues. It is characterized by inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 of the lung parenchyma
Parenchyma
Parenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour"...

 leading to impaired gas exchange
Gas exchange
Gas exchange is a process in biology where gases contained in an organism and atmosphere transfer or exchange. In human gas-exchange, gases contained in the blood of human bodies exchange with gases contained in the atmosphere. Human gas-exchange occurs in the lungs...

 with concomitant systemic release of inflammatory mediators causing inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

, hypoxemia
Hypoxemia
Hypoxemia is generally defined as decreased partial pressure of oxygen in blood, sometimes specifically as less than or causing hemoglobin oxygen saturation of less than 90%.-Distinction from anemia and hypoxia:...

 and frequently resulting in multiple organ failure. This condition is often fatal, usually requiring mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

 and admission to an intensive care unit
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...

. A less severe form is called acute lung injury
Acute lung injury
Acute lung injury is a diffuse heterogeneous lung injury characterized by hypoxemia, non cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage...

 (ALI).

ARDS formerly most commonly signified adult respiratory distress syndrome to differentiate it from infant respiratory distress syndrome
Infant respiratory distress syndrome
Infant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome in premature infants caused by developmental insufficiency of surfactant production and structural...

 in premature infants. However, as this type of pulmonary edema also occurs in children,
ARDS has gradually shifted to mean acute rather than adult. The differences with the typical infant syndrome remain.

Signs and symptoms

People usually present with shortness of breath, tachypnea
Tachypnea
Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...

 and occasionally with confusion resulting from low oxygen levels.

ARDS can occur within 24 to 48 hours of an injury (trauma, burns, aspiration, massive blood transfusion, drug/alcohol abuse) or an acute illness (infectious pneumonia, sepsis, acute pancreatitis).

ARDS is characterized by:
  • Acute onset
  • Bilateral infiltrates on chest radiograph sparing costophrenic angles
  • Pulmonary artery wedge pressure < 18 mmHg (obtained by pulmonary artery catheter
    Pulmonary artery catheter
    In medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. Its purpose is diagnostic; it is used to detect heart failure or sepsis, monitor therapy, and evaluate the effects of drugs...

    ization), if this information is available; if unavailable, then lack of clinical evidence of left ventricular failure suffices
  • if PaO2:FiO2 < 300 mmHg (40 kPa) acute lung injury
    Acute lung injury
    Acute lung injury is a diffuse heterogeneous lung injury characterized by hypoxemia, non cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage...

     (ALI) is considered to be present
  • if PaO2:FiO2 < 200 mmHg (26.7 kPa) acute respiratory distress syndrome (ARDS) is considered to be present


The PaO2:FiO2 ratios above refer to the gradient between the inspired oxygen level and the oxygen that is present in the blood. The lower the ratio, the less inspired oxygen is getting into the blood, and so the worse the patient's condition - so ARDS represents a more severe progression of disease from ALI by these diagnostic criteria.

To summarize and simplify, ARDS is an acute (rapid onset) syndrome (collection of symptoms) that affects the lungs widely and results in a severe oxygenation defect, but is not due to heart failure.

Cause

Some cases of ARDS are linked to large volumes of fluid used during resuscitation post trauma.

Diagnosis

An arterial blood gas
Arterial blood gas
An arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...

 analysis and chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...

 allow formal diagnosis by the aforementioned criteria. Although severe hypoxemia is generally included, the appropriate threshold defining abnormal PaO2 has never been systematically studied. Note though, that a severe oxygenation defect is not synonymous with ventilatory support. Any PaO2 below 100 (generally saturation less than 100%) on a supplemental oxygen fraction of 50% meets criteria for ARDS. This can easily be achieved by high flow oxygen supplementation without ventilatory support.

Any cardiogenic cause of pulmonary edema should be excluded. This can be done by placing a pulmonary artery catheter
Pulmonary artery catheter
In medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. Its purpose is diagnostic; it is used to detect heart failure or sepsis, monitor therapy, and evaluate the effects of drugs...

 for measuring the pulmonary artery wedge pressure. However, this is not necessary and is now rarely done as abundant evidence has emerged demonstrating that the use of pulmonary artery catheters does not lead to improved patient outcomes in critical illness including ARDS.

Plain chest X-rays are sufficient to document bilateral alveolar infiltrates in the majority of cases. While CT scanning leads to more accurate images of the pulmonary parenchyma in ARDS, it has little utility in the clinical management of patients with ARDS, and remains largely a research tool.

Four main criteria for ARDS:
1) Hypoxia
2) Chest X-Ray: Bilateral diffuse infiltrates of the lungs
3) No cardiovascular lesion
4) PF ratio is less than 200

Pathophysiology

ARDS is a clinical syndrome associated with a variety of pathological findings. These include pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD.

DAD is characterized by a diffuse inflammation of lung parenchyma. The triggering insult to the parenchyma usually results in an initial release of cytokines and other inflammatory mediators, secreted by local epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 and endothelial
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...

 cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

.

Neutrophils and some T-lymphocytes quickly migrate into the inflamed lung parynchema and contribute in the amplification of the phenomenon.

Typical histological presentation involves diffuse alveolar
Pulmonary alveolus
An alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung parenchyma, the pulmonary alveoli are the dead ends of the respiratory tree, which outcrop from either alveolar sacs or alveolar ducts, which are both sites of gas exchange with the blood as well...

 damage and hyaline
Hyaline
The term hyaline denotes a substance with a glass-like appearance.-Histopathology:In histopathological medical usage, a hyaline substance appears glassy and pink after being stained with haematoxylin and eosin — usually it is an acellular, proteinaceous material...

 membrane formation in alveolar walls.

Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress.

Inflammation

Inflammation alone, as in sepsis, causes endothelial dysfunction, fluid extravasation from the capillaries
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...

 and impaired drainage of fluid from the lungs. Dysfunction of type II pulmonary epithelial cells may also be present, with a concomitant reduction in surfactant
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...

 production. Elevated inspired oxygen concentration often becomes necessary at this stage, and may facilitate a 'respiratory burst
Respiratory burst
Respiratory burst is the rapid release of reactive oxygen species from different types of cells....

' in immune cells.

In a secondary phase, endothelial dysfunction causes cells and inflammatory exudate to enter the alveoli. This pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...

 increases the thickness of the alveolo-capillary space, increasing the distance the oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 must diffuse to reach blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

. This impairs gas exchange leading to hypoxia, increases the work of breathing, eventually induces fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

 of the airspace.

Moreover, edema and decreased surfactant production by type II pneumocytes may cause whole alveoli
Pulmonary alveolus
An alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung parenchyma, the pulmonary alveoli are the dead ends of the respiratory tree, which outcrop from either alveolar sacs or alveolar ducts, which are both sites of gas exchange with the blood as well...

 to collapse, or to completely flood. This loss of aeration contributes further to the right-to-left shunt
Right-to-left shunt
A right-to-left shunt is a cardiac shunt which allows blood to flow from the right heart to the left heart. This terminology is used both for the abnormal state in humans and for normal physiological shunts in reptiles...

 in ARDS. As the alveoli contain progressively less gas, the blood flowing through the alveolar capillaries is progressively less oxygenated, resulting in massive intrapulmonary shunting.

Collapsed alveoli (and small bronchi) do not allow gas exchange. It is not uncommon to see patients with a PaO2 of 60 mmHg (8.0 kPa) despite mechanical ventilation with 100% inspired oxygen.

The loss of aeration may follow different patterns according to the nature of the underlying disease, and other factors. In pneumonia-induced ARDS, for example, large, more commonly causes relatively compact areas of alveolar infiltrates. These are usually distributed to the lower lobes
Lobe (anatomy)
In anatomy, a lobe is a clear anatomical division or extension that can be determined without the use of a microscope This is in contrast to a lobule, which is a clear division only visible histologically....

, in their posterior segments, and they roughly correspond to the initial infected area.

In sepsis or trauma-induced ARDS, infiltrates are usually more patchy and diffuse. The posterior and basal segments are always more affected, but the distribution is even less homogeneous.

Loss of aeration also causes important changes in lung mechanical properties. These alterations are fundamental in the process of inflammation amplification and progression to ARDS in mechanically ventilated patients.

Mechanical stress

Mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

 is an essential part of the treatment of ARDS. As loss of aeration (and the underlying disease) progress, the end tidal volume eventually grows to a level incompatible with life. Thus, mechanical ventilation is initiated to relieve respiratory muscles of their work, and to protect the usually obtunded patient's airway
Airway
The pulmonary airway comprises those parts of the respiratory system through which air flows, conceptually beginning at the nose and mouth, and terminating in the alveoli...

s.

However, mechanical ventilation may constitute a risk factor for the development, or the worsening, of ARDS.

Aside from the infectious complications arising from invasive ventilation with tracheal intubation
Tracheal intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...

, positive-pressure ventilation directly alters lung mechanics during ARDS. The result is higher mortality, i.e. through baro-trauma, when these techniques are used.

In 1998, Amato et al. published a paper showing substantial improvement in the outcome of patients ventilated with lower tidal volume
Tidal volume
Tidal volume is the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied.Typical values are around 500ml or 7ml/kg bodyweight.-Mechanical Ventilation:...

s (
Vt) (6 mL·kg−1). This result was confirmed in a 2000 study sponsored by the NIH
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

. Although both these studies were widely criticized for several reasons, and although the authors were not the first to experiment lower-volume ventilation, they shed new light on the relationship between mechanical ventilation and ARDS.

One opinion is that the forces applied to the lung by the ventilator may work as a lever to induce further damage to lung parenchyma. It appears that shear stress
Shear stress
A shear stress, denoted \tau\, , is defined as the component of stress coplanar with a material cross section. Shear stress arises from the force vector component parallel to the cross section...

 at the interface
Interface (chemistry)
An interface is a surface forming a common boundary among two different phases, such as an insoluble solid and a liquid, two immiscible liquids or a liquid and an insoluble gas. The importance of the interface depends on which type of system is being treated: the bigger the quotient area/volume,...

 between collapsed and aerated units may result in the breakdown of aerated units, which inflate asymmetrically due to the 'stickiness' of surrounding flooded alveoli. The fewer such interfaces around an alveolus, the lesser the stress.

Indeed, even relatively low stress forces may induce signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 systems at the cellular level, thus inducing the release of inflammatory mediators.

This form of stress is thought to be applied by the transpulmonary pressure
Transpulmonary pressure
Transpulmonary pressure is a term used to describe the difference between the alveolar pressure and the intrapleural pressure in the lungs. During human ventilation, air flows because of pressure gradients.Ptp = Palv - Pip...

 (gradient
Gradient
In vector calculus, the gradient of a scalar field is a vector field that points in the direction of the greatest rate of increase of the scalar field, and whose magnitude is the greatest rate of change....

) (Pl) generated by the ventilator or, better, its cyclical variations. The better outcome obtained in patients ventilated with lower Vt may be interpreted as a beneficial effect of the lower Pl. Transpulmonary pressure
Pressure
Pressure is the force per unit area applied in a direction perpendicular to the surface of an object. Gauge pressure is the pressure relative to the local atmospheric or ambient pressure.- Definition :...

, is an indirect function
Function (mathematics)
In mathematics, a function associates one quantity, the argument of the function, also known as the input, with another quantity, the value of the function, also known as the output. A function assigns exactly one output to each input. The argument and the value may be real numbers, but they can...

 of the
Vt setting on the ventilator, and only trial patients with plateau pressures (a surrogate for the actual Pl) were less than 32 cmH2O
Centimetre of water
A centimetre of water is a less commonly used unit of pressure derived from pressure head calculations using metrology...

 (3.1 kPa) had improved survival.

The way
Pl is applied on alveolar surface determines the shear stress to which lung units are exposed. ARDS is characterized by a usually inhomogeneous reduction of the airspace, and thus by a tendency towards higher Pl at the same Vt, and towards higher stress on less diseased units.

The inhomogeneity of alveoli at different stages of disease is further increased by the gravitational gradient to which they are exposed, and the different perfusion pressures at which blood flows through them. Finally, abdominal pressure exerts an additional pressure on inferoposterior lung segments, favoring compression and collapse of those units.

The different mechanical properties of alveoli in ARDS may be interpreted as having varying time constants (the product of alveolar compliance × resistance). A long time constant indicates an alveolus which opens slowly during tidal inflation, as a consequence of contrasting pressure around it, or altered water-air interface inside it (loss of surfactant, flooding).

Slow alveoli are said to be 'kept open' using positive end-expiratory pressure
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

, a feature of modern ventilators which maintains a positive airway pressure throughout the whole respiratory cycle. A higher mean pressure cycle-wide slows the collapse of diseased units, but it has to be weighed against the corresponding elevation in Pl/plateau pressure. Newer ventilatory approaches attempt to maximize mean airway pressure for its ability to 'recruit' collapsed lung units while minimizing the shear stress caused by frequent openings and closings of aerated units.

The prone position
Prone position
The term means to lie on bed or ground in a position with chest downwards and back upwards.-Etymology :The word "prone," meaning "naturally inclined to something, apt, liable," has been recorded in English since 1382; the meaning "lying face-down" was first recorded in 1578, but is also referred to...

 also reduces the inhomogeneity in alveolar time constants induced by gravity and edema. If clinically appropriate, mobilization of the ventilated patient can assist in achieving the same goal.

Stress Index

Mechanical ventilation can exacerbate the inflammatory response in patients with ARDS by including cyclic tidal alveolar hyperinflation and/or recruiting/derecruiting.
Stress index is measured during constant-flow assist-control mechanical ventilation without changing the baseline ventilatory pattern. Identifying the steadiest portion of the inspiratory flow (F) waveform fit the corresponding portion of the airway pressure (Paw) waveform in the following power equation.

Paw = a × tb + c

where the coefficient b, the “Stress Index,” describes the shape of the curve. The Stress Index depict a constant compliance if the value is around 1, an increasing compliance during the inspiration if the value is below 1, and a decreasing compliance if the value is above 1.

Raniery, Grasso, et al. set a strategy guided by the stress index with the following rules:
  • Stress Index below 0.9, PEEP was increased
  • Stress Index between 0.9 and 1.1, no change was made
  • Stress Index above 1.1 PEEP was decreased.
  • Adjustment of PEEP was suspended if any one of the following conditions ensued: plateau pressure > 30cmH2O, SaO2 < 88%, or hemodynamic instability.


Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement.

Progression

If the underlying disease or injurious factor is not removed, the amount of inflammatory mediators released by the lungs in ARDS may result in a systemic inflammatory response syndrome
Systemic inflammatory response syndrome
Systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently a response of the immune system to infection, but not necessarily so...

 (or sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...

 if there is lung infection). The evolution towards shock and/or multiple organ failure follows paths analogous to the pathophysiology of sepsis.

This adds up to the impaired oxygenation which is the central problem of ARDS, as well as to respiratory acidosis
Respiratory acidosis
Respiratory acidosis is a medical condition in which decreased ventilation causes increased blood carbon dioxide concentration and decreased pH ....

, which is often caused by ventilation techniques such as permissive hypercapnia
Permissive hypercapnia
Permissive hypercapnia is hypercapnia, , in respiratory insufficient patients in which oxygenation has become so difficult that the optimal mode of mechanical ventilation is not capable of exchanging enough carbon dioxide...

 which attempt to limit ventilator-induced lung injury in ARDS.

The result is a critical illness in which the 'endothelial disease' of severe sepsis/SIRS is worsened by the pulmonary dysfunction, which further impairs oxygen delivery.

Treatment

Acute respiratory distress syndrome is usually treated with mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

 in the Intensive Care Unit. Ventilation is usually delivered through oro-tracheal intubation
Intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...

, or tracheostomy
Tracheotomy
Among the oldest described surgical procedures, tracheotomy consists of making an incision on the anterior aspect of the neck and opening a direct airway through an incision in the trachea...

 whenever prolonged ventilation (≥2 weeks) is deemed inevitable.

The possibilities of non-invasive ventilation are limited to the very early period of the disease or, better, to prevention in individuals at risk for the development of the disease (atypical pneumonia
Atypical pneumonia
Atypical pneumonia aka "walking pneumonia" is a pneumonia not caused by one of the more traditional pathogens, and with a clinical presentation inconsistent with typical pneumonia. It can be caused by a variety of microorganisms...

s, pulmonary contusion
Pulmonary contusion
A pulmonary contusion is a contusion of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels...

, major surgery patients).

Treatment of the underlying cause is imperative, as it tends to maintain the ARDS picture.

Appropriate antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

 therapy must be administered as soon as microbiological culture
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...

 results are available. Empirical
Empirical
The word empirical denotes information gained by means of observation or experimentation. Empirical data are data produced by an experiment or observation....

 therapy may be appropriate if local microbiological surveillance is efficient. More than 60% ARDS patients experience a (nosocomial) pulmonary infection either before or after the onset of lung injury.

The origin of infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

, when surgically treatable, must be operated on. When sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...

 is diagnosed, appropriate local protocols
Guideline (medical)
A medical guideline is a document with the aim of guiding decisions and criteria regarding diagnosis, management, and treatment in specific areas of healthcare...

 should be enacted.

Commonly used supportive therapy includes particular techniques of mechanical ventilation and pharmacological agents whose effectiveness with respect to the outcome has not yet been proven. It is now debated whether mechanical ventilation is to be considered mere supportive therapy or actual treatment, since it may substantially affect survival.

Mechanical ventilation

The overall goal is to maintain acceptable gas exchange and to minimize adverse effects in its application. Three parameters are used: PEEP (positive end-expiratory pressure, to maintain maximal recruitment of alveolar units), mean airway pressure (to promote recruitment and predictor of hemodynamic effects) and plateau pressure (best predictor of alveolar overdistention).

Conventional therapy aimed at tidal volume
Tidal volume
Tidal volume is the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied.Typical values are around 500ml or 7ml/kg bodyweight.-Mechanical Ventilation:...

s (Vt) of 12-15 ml/kg. Recent studies have shown that high tidal volumes can overstretch alveoli resulting in volutrauma (secondary lung injury). The ARDS Clinical Network, or ARDSNet, completed a landmark trial that showed improved mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

 when ventilated with a tidal volume of 6 ml/kg compared to the traditional 12 ml/kg. Low tidal volumes (Vt) may cause hypercapnia
Permissive hypercapnia
Permissive hypercapnia is hypercapnia, , in respiratory insufficient patients in which oxygenation has become so difficult that the optimal mode of mechanical ventilation is not capable of exchanging enough carbon dioxide...

 and atelectasis
Atelectasis
Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation.It is a very common finding in chest x-rays and other...

 due to their inherent tendency to increase dead space.

Low tidal volume ventilation was the primary independent variable associated with reduced mortality in the NIH-sponsored ARDSnet trial of tidal volume in ARDS. Plateau pressure less than 30 cm H2O was a secondary goal, and subsequent analyses of the data from the ARDSnet trial (as well as other experimental data) demonstrate that there appears to be NO safe upper limit to plateau pressure; that is, regardless of plateau pressure, patients fare better with low tidal volumes (see Hager et al., American Journal of Respiratory and Critical Care Medicine, 2005).

APRV (Airway Pressure Release Ventilation) and ARDS / ALI

It is often said that no particular ventilator mode is known to improve mortality in ARDS. The landmark ARDSNet trial used a volume controlled mode comparing delivered tidal volumes of 6 ml/kg with 12 ml/kg and showed decrease mortality with smaller volumes and typically higher set rates. However, other modes of ventilation, like airway pressure release ventilation (APRV), have not been directly compared to volume controlled ventilation*.

Some practitioners favor APRV when treating ARDS. Well documented advantages to APRV ventilation include: decreased airway pressures, decreased minute ventilation, decreased dead-space ventilation, promotion of spontaneous breathing, almost 24 hour a day alveolar recruitment, decreased use of sedation, near elimination of neuromuscular blockade, optimized arterial blood gas results, mechanical restoration of FRC (functional residual capacity), a positive effect on cardiac output (due to the negative inflection from the elevated baseline with each spontaneous breath), increased organ and tissue perfusion and potential for increased urine output secondary to increased renal perfusion.

A patient with ARDS, on average, spends between 8 and 11 days on a mechanical ventilator; APRV may reduce this time significantly and conserve valuable resources.
  • A proposed sturdy to compare APRV to the ARDSNet Protocol is set for December 2011: http://clinicaltrials.gov/ct2/show/NCT00793013

Positive end-expiratory pressure

Positive end-expiratory pressure
Positive end-expiratory pressure
Positive end-expiratory pressure is the pressure in the lungs above atmospheric pressure that exists at the end of expiration...

 (PEEP) is used in mechanically-ventilated patients with ARDS to improve oxygenation. In ARDS, three populations of alveoli can be distinguished. There are normal alveoli which are always inflated and engaging in gas exchange, flooded alveoli which can never, under any ventilatory regime, be used for gas exchange, and atelectatic or partially flooded alveoli that can be "recruited" to participate in gas exchange under certain ventilatory regimens. The recruitable aveoli represent a continuous population, some of which can be recruited with minimal PEEP, and others which can only be recruited with high levels of PEEP. An additional complication is that some or perhaps most alveoli can only be opened with higher airway pressures than are needed to keep them open. Hence the justification for maneuvers where PEEP is increased to very high levels for seconds to minutes before dropping the PEEP to a lower level. Finally, PEEP can be harmful. High PEEP necessarily increases mean airway pressure and alveolar pressure. This in turn can damage normal alveoli by overdistension resulting in DAD.

The 'best PEEP' used to be defined as 'some' cmH2O above the lower inflection point (LIP) in the sigmoidal
Sigmoid function
Many natural processes, including those of complex system learning curves, exhibit a progression from small beginnings that accelerates and approaches a climax over time. When a detailed description is lacking, a sigmoid function is often used. A sigmoid curve is produced by a mathematical...

 pressure-volume relationship curve of the lung. Recent research has shown that the LIP-point pressure is no better than any pressure above it, as recruitment of collapsed alveoli, and more importantly the overdistension of aerated units, occur throughout the whole inflation. Despite the awkwardness of most procedures used to trace the pressure-volume curve, it is still used by some to define the minimum PEEP to be applied to their patients. Some of the newest ventilators have the ability to automatically plot a pressure-volume curve. The possibility of having an 'instantaneous' tracing trigger might produce renewed interest in this analysis.

PEEP may also be set empirically. Some authors suggest performing a 'recruiting maneuver' (i.e., a short time at a very high continuous positive airway pressure, such as 50 cmH2O (4.9 kPa), to recruit, or open, collapsed units with a high distending pressure) before restoring previous ventilation. The final PEEP level should be the one just before the drop in PaO2 (or peripheral blood oxygen saturation
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

) during a step-down trial.

Intrinsic PEEP (iPEEP), or auto-PEEP, first described by John Marini of St. Paul Regions Hospital, is a potentially unrecognized contributor to PEEP in patients. When ventilating at high frequencies, its contribution can be substantial, particularly in patients with obstructive lung disease. iPEEP has been measured in very few formal studies on ventilation in ARDS patients, and its contribution is largely unknown. Its measurement is recommended in the treatment of ARDS patients, especially when using high-frequency (oscillatory/jet) ventilation
High-frequency ventilation
High frequency ventilation is a type of mechanical ventilation that employs very high respiratory rates and very small tidal volumes. High frequency ventilation is thought to reduce ventilator-associated lung injury , especially in the context of ARDS and acute lung injury. This is commonly...

.

A compromise between the beneficial and adverse effects of PEEP is inevitable.

Prone position

Distribution of lung infiltrates in acute respiratory distress syndrome is non-uniform. Repositioning into the prone position (face down) might improve oxygenation by relieving atelectasis
Atelectasis
Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation.It is a very common finding in chest x-rays and other...

 and improving perfusion. However, although the hypoxemia is overcome there seems to be no effect on overall survival.

Fluid management

Several studies have shown that pulmonary function and outcome are better in patients that lost weight or pulmonary wedge pressure was lowered by diuresis
Diuresis
Diuresis may refer to:* Urine production, as an aspect of fluid balance* Excessive urine production - see polyuria* Immersion diuresis...

 or fluid restriction.

Corticosteroids

A Meduri et al. study has found significant improvement in ARDS using modest doses of corticosteroids. The initial regimen consists of methylprednisolone
Methylprednisolone
Methylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....

 2 mg/kg daily. After 3–5 days a response must be apparent. In 1–2 weeks the dose can be tapered to methylprednisolone 0.5-1.0 mg daily. Patients with ARDS do not benefit from high-dose corticosteroids. This was a study involving a small number of patients in one center. A recent NIH-sponsored multicenter ARDSnet LAZARUS study of corticosteroids for ARDS demonstrated that they are not efficacious in ARDS.

Nitric oxide

Inhaled nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...

 (NO) potentially acts as selective pulmonary vasodilator. Rapid binding to hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

 prevents systemic effects. It should increase perfusion of better ventilated areas. There are no large studies demonstrating positive results. Therefore its use must be considered individually.

Almitrine bismesylate stimulates chemoreceptors in carotic and aortic bodies. It has been used to potentiate the effect of NO, presumably by potentiating hypoxia-induced pulmonary vasoconstriction. In case of ARDS it is not known whether this combination is useful.

Surfactant therapy

To date no prospective controlled clinical trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

 has shown a significant mortality benefit of exogenous surfactant in adult ARDS.

Complications

Since ARDS is an extremely serious condition which requires invasive forms of therapy it is not without risk. Complications to be considered are:
  • Pulmonary: barotrauma
    Barotrauma
    Barotrauma is physical damage to body tissues caused by a difference in pressure between an air space inside or beside the body and the surrounding fluid...

     (volutrauma), pulmonary embolism
    Pulmonary embolism
    Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...

     (PE), pulmonary fibrosis, ventilator-associated pneumonia
    Ventilator-associated pneumonia
    Ventilator-associated pneumonia is a sub-type of hospital-acquired pneumonia which occurs in people who are receiving mechanical ventilation. VAP is not characterized by the causative agents; rather, as its name implies, definition of VAP is restricted to patients undergoing mechanical...

     (VAP).
  • Gastrointestinal: hemorrhage (ulcer), dysmotility, pneumoperitoneum, bacterial translocation.
  • Cardiac: arrhythmias, myocardial dysfunction.
  • Renal: acute renal failure
    Acute renal failure
    Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...

     (ARF), positive fluid balance.
  • Mechanical: vascular injury, pneumothorax (by placing pulmonary artery catheter), tracheal injury/stenosis (result of intubation and/or irritation by endotracheal tube.
  • Nutritional: malnutrition (catabolic state), electrolyte deficiency.

Epidemiology

The annual incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 of ARDS is 1.5–13.5 people per 100,000 in the general population. Its incidence in the intensive care unit
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...

 (ICU), mechanically ventilated
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

 population is much higher. Brun-Buisson et al. (2004) reported a prevalence of acute lung injury (ALI) (see below) of 16.1% percent in ventilated patients admitted for more than 4 hours. More than half these patients may develop ARDS.

Mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...

, sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...

, pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

, shock, aspiration
Pulmonary aspiration
Pulmonary aspiration is the entry of material from the oropharynx or gastrointestinal tract into the larynx and lower respiratory tract...

, trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

 (especially pulmonary contusion
Pulmonary contusion
A pulmonary contusion is a contusion of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels...

), major surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

, massive transfusions
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

, smoke inhalation
Smoke inhalation
Smoke inhalation is the primary cause of death in victims of indoor fires.Smoke inhalation injury refers to injury due to inhalation or exposure to hot gaseous products of combustion. This can cause serious respiratory complications....

, drug reaction or overdose, fat emboli and reperfusion pulmonary edema after lung transplantation
Lung transplantation
Lung transplantation, or pulmonary transplantation is a surgical procedure in which a patient's diseased lungs are partially or totally replaced by lungs which come from a donor...

 or pulmonary embolectomy may all trigger ARDS. Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients. Pneumonia and sepsis may be either causes or complications of ARDS.

Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation.

The mortality rate
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

 varies from 30% to 85%. Usually, randomized controlled trials in the literature show lower death rates, both in control and treatment patients. This is thought to be due to stricter enrollment criteria. Observational studies generally report 50%–60% mortality.

History

Acute respiratory distress syndrome was first described in 1967 by Ashbaugh et al. Initially there was no definition, resulting in controversy over incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 and mortality
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

. In 1988 an expanded definition was proposed which quantified physiologic respiratory impairment.

In 1994 a new definition was recommended by the American-European Consensus Conference Committee. It had two advantages: first, it recognizes that severity of pulmonary injury varies, and secondly, it is simple to use.

ARDS was defined as the ratio of arterial partial oxygen tension (PaO2) as fraction of inspired oxygen (FiO2)
FiO2
FiO2, in the field of medicine, is the fraction of inspired oxygen in a gas mixture.The FiO2 is expressed as a number from 0 to 1 .The FiO2 of normal room air is 0.21 ....

 below 200 mmHg in the presence of bilateralinfiltrate
Infiltration (medical)
Infiltration is the diffusion or accumulation of substances not normal to it or in amounts in excess of the normal. The material collected in those tissues or cells is called infiltrate.-Classification:...

s on the chest x-ray. These infiltrates may appear similar to those of left ventricular failure, but the cardiac silhouette appears normal in ARDS. Also, the pulmonary capillary wedge pressure is normal (less than 18 mmHg) in ARDS, but raised in left ventricular failure.

A PaO2/FiO2 ratio less than 300 mmHg with bilateral infiltrates indicatesacute lung injury
Acute lung injury
Acute lung injury is a diffuse heterogeneous lung injury characterized by hypoxemia, non cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage...

(ALI). Although formally considered different from ARDS, ALI is usually just a precursor to ARDS.

External links

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