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Acute respiratory distress syndrome (ARDS) is a type of
respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...
characterized by rapid onset of widespread
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
in the
lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...
. Symptoms include
shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
(dyspnea),
rapid breathing Tachypnea, also spelt tachypnoea, is a respiratory rate greater than normal, resulting in abnormally rapid and shallow breathing. In adult humans at rest, any respiratory rate of 1220 per minute is considered clinically normal, with tachypnea b ...
(tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased
quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
is common. Causes may include
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
,
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...
,
trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...
,
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
, and aspiration. The underlying mechanism involves diffuse injury to cells which form the barrier of the microscopic air sacs of the lungs,
surfactant Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...
dysfunction, activation of the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
, and dysfunction of the body's regulation of
blood clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
. In effect, ARDS impairs the lungs' ability to exchange
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
and
carbon dioxide Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...
. Adult diagnosis is based on a PaO2/FiO2 ratio (ratio of partial pressure arterial oxygen and fraction of inspired oxygen) of less than 300 mm Hg despite a
positive end-expiratory pressure Positive end-expiratory pressure (PEEP) is the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration. The two types of PEEP are extrinsic PEEP (PEEP applied by ...
(PEEP) of more than 5 cm H2O.
Cardiogenic pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due to ...
, as the cause, must be excluded. The primary treatment involves
mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air ...
together with treatments directed at the underlying cause. Ventilation strategies include using low volumes and low pressures. If oxygenation remains insufficient,
lung recruitment maneuver Lung recruitment maneuvers are efforts to open collapsed areas of the lungs and keep them open. They are primarily used in acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure chara ...
s and
neuromuscular blockers Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors. In clin ...
may be used. If these are insufficient,
extracorporeal membrane oxygenation Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support (ECLS), is an extracorporeal technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequat ...
(ECMO) may be an option. The syndrome is associated with a death rate between 35 and 50%. Globally, ARDS affects more than 3 million people a year. The condition was first described in 1967. Although the terminology of "adult respiratory distress syndrome" has at times been used to differentiate ARDS from "
infant respiratory distress syndrome Infantile respiratory distress syndrome (IRDS), also called respiratory distress syndrome of newborn, or increasingly surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants c ...
" in newborns, the international consensus is that "acute respiratory distress syndrome" is the best term because ARDS can affect people of all ages. There are separate diagnostic criteria for children and those in areas of the world with fewer resources.


Signs and symptoms

The signs and symptoms of ARDS often begin within two hours of an inciting event, but have been known to take as long as 1–3 days; diagnostic criteria require a known insult to have happened within 7 days of the syndrome. Signs and symptoms may include
shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
,
fast breathing Hyperventilation is irregular breathing that occurs when the rate or tidal volume of breathing eliminates more carbon dioxide than the body can produce. This leads to hypocapnia, a reduced concentration of carbon dioxide dissolved in the blood. T ...
, and a low oxygen level in the blood due to abnormal ventilation.Marino (2006), pp 435 Other common symptoms include muscle fatigue and general weakness, low blood pressure, a dry, hacking cough, and fever.


Complications

Complications may include the following: * Lungs:
barotrauma Barotrauma is physical damage to body tissues caused by a difference in pressure between a gas space inside, or contact with, the body and the surrounding gas or liquid. The initial damage is usually due to over-stretching the tissues in tensio ...
(volutrauma),
pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
(PE),
pulmonary fibrosis Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failu ...
,
ventilator-associated pneumonia Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals. As such, VAP typically affects critically ill persons that are in an intensive care unit (I ...
(VAP) * Gastrointestinal: bleeding (ulcer), dysmotility,
pneumoperitoneum Pneumoperitoneum is pneumatosis (abnormal presence of air or other gas) in the peritoneal cavity, a potential space within the abdominal cavity. The most common cause is a perforated abdominal organ, generally from a perforated peptic ulcer, althou ...
, bacterial translocation * Neurological:
hypoxic Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the t ...
brain damage Neurotrauma, brain damage or brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating t ...
* Cardiac: abnormal heart rhythms, myocardial dysfunction * Kidney:
acute kidney failure Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cla ...
, positive fluid balance * Mechanical: vascular injury,
pneumothorax A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve ...
(by placing
pulmonary artery A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and t ...
catheter In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
), tracheal injury/stenosis (result of intubation and/or irritation by
endotracheal tube A tracheal tube is a catheter that is inserted into the trachea for the primary purpose of establishing and maintaining a patent airway and to ensure the adequate exchange of oxygen and carbon dioxide. Many different types of tracheal tubes are a ...
) * Nutritional:
malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...
( catabolic state),
electrolyte abnormalities Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...
Other complications that are typically associated with ARDS include: *
Atelectasis Atelectasis is the collapse or closure of a lung resulting in reduced or absent gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the alveoli are deflated down to little or no volume, as distinct ...
: small air pockets within the
lung collapse A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve ...
* Complications that arise from treatment in a hospital: blood clots formed by lying down for long periods of time, weakness in muscles that are used for breathing, stress ulcers, and issues with mental health and depression. * Failure of multiple organs * Pulmonary hypertension or increase in
blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
in the main artery from the heart to the lungs. This complication typically occurs due to the restriction of the blood vessel due to inflammation of the mechanical ventilation


Causes

There are ''direct'' and ''indirect'' causes of ARDS depending whether the lungs are initially affected. Direct causes include
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
(including bacterial and viral), aspiration, inhalational lung injury, lung contusion, chest trauma, and near-drowning. Indirect causes include
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
,
shock Shock may refer to: Common uses Collective noun *Shock, a historic commercial term for a group of 60, see English numerals#Special names * Stook, or shock of grain, stacked sheaves Healthcare * Shock (circulatory), circulatory medical emergen ...
,
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...
,
trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...
(e.g. fat embolism),
cardiopulmonary bypass Cardiopulmonary bypass (CPB) is a technique in which a machine temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and oxygen to the body. The CPB pump itself is often referred to as a he ...
,
TRALI Transfusion-related acute lung injury (TRALI) is the serious complication of transfusion of blood products that is characterized by the rapid onset of excess fluid in the lungs. It can cause dangerous drops in the supply of oxygen to body tiss ...
, burns, increased
intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
. Fewer cases of ARDS are linked to large volumes of fluid used during post-trauma resuscitation.


Pathophysiology

ARDS is a form of fluid accumulation in the lungs not explained by heart failure (noncardiogenic pulmonary edema). It is typically provoked by an acute injury to the lungs that results in flooding of the lungs' microscopic air sacs responsible for the exchange of gases such as oxygen and carbon dioxide with
capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
in the lungs. Additional common findings in ARDS include partial collapse of the lungs (
atelectasis Atelectasis is the collapse or closure of a lung resulting in reduced or absent gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the alveoli are deflated down to little or no volume, as distinct ...
) and low levels of oxygen in the blood (
hypoxemia Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia has many causes, and often causes hypoxia as the blood is not supplying enough oxygen to the tissues of the body ...
). The clinical syndrome is associated with pathological findings including pneumonia,
eosinophilic pneumonia Eosinophilic pneumonia is a disease in which an eosinophil, a type of white blood cell, accumulates in the lungs. These cells cause disruption of the normal air spaces (alveoli) where oxygen is extracted from the atmosphere. Several different kind ...
,
cryptogenic organizing pneumonia Cryptogenic organizing pneumonia (COP), formerly known as bronchiolitis obliterans organizing pneumonia (BOOP), is an inflammation of the bronchioles (bronchiolitis) and surrounding tissue in the lungs. It is a form of idiopathic interstitial pneu ...
, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of chemical signals and other inflammatory mediators secreted by local
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
and
endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
cells.
Neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
and some T-
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
quickly migrate into the inflamed lung tissue and contribute in the amplification of the phenomenon. The typical histological presentation involves diffuse
alveolar Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * ...
damage and
hyaline A hyaline substance is one with a glassy appearance. The word is derived from el, ὑάλινος, translit=hyálinos, lit=transparent, and el, ὕαλος, translit=hýalos, lit=crystal, glass, label=none. Histopathology Hyaline cartilage is ...
membrane formation in alveolar walls. Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress. In addition, in broncho-alveolar lavage fluids of ARDS, it can be observed trichomonads, which are unicellular flagellated parasites of the order
Trichomonadida Trichomonadida is an order of anaerobic protists, included with the parabasalids. Members of this order are referred to as trichomonads. Some organisms in this order include: *''Trichomonas vaginalis'', an organism living inside the vagina of h ...
. These trichomonads occur in an amoeboid form, without flagellum, which makes it difficult to identify them under the microscope. The colonization of the alveolar spaces by the parasite is a secondary phenomenon, frequent beyond D5, probably favored by the local hypoxia of the DAD. The amoeboid transformation is an argument in favor of a deleterious action of the parasite, which nevertheless remains conjectural.


Diagnosis


Diagnostic criteria

Diagnostic criteria for ARDS have changed over time as understanding of the
pathophysiology Pathophysiology ( physiopathology) â€“ a convergence of pathology with physiology â€“ is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...
has evolved. The international consensus criteria for ARDS were most recently updated in 2012 and are known as the "Berlin definition". In addition to generally broadening the diagnostic thresholds, other notable changes from the prior 1994 consensus criteria include discouraging the term "acute lung injury," and defining grades of ARDS severity according to degree of decrease in the oxygen content of the blood. According to the 2012 Berlin definition, adult ARDS is characterized by the following: * lung injury of acute onset, within 1 week of an apparent clinical insult and with the progression of respiratory symptoms * bilateral opacities on chest imaging (
chest radiograph A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
or CT) not explained by other
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
pathology (e.g.
effusion In physics and chemistry, effusion is the process in which a gas escapes from a container through a hole of diameter considerably smaller than the mean free path of the molecules. Such a hole is often described as a ''pinhole'' and the escape ...
, lobar/lung collapse, or nodules) * respiratory failure not explained by heart failure or volume overload * decreased Pa/Fi ratio (a decreased Pa/Fi ratio indicates reduced arterial oxygenation from the available inhaled gas): ** ''mild ARDS'': 201 – 300 mmHg (≤ 39.9 kPa) ** ''moderate ARDS'': 101 – 200 mmHg (≤ 26.6 kPa) ** ''severe ARDS'': ≤ 100 mmHg (≤ 13.3 kPa) ** Note that the Berlin definition requires a minimum positive end expiratory pressure (PEEP) of 5 cm for consideration of the Pa/Fi ratio. This degree of PEEP may be delivered noninvasively with
CPAP Continuous positive airway pressure (CPAP) is a form of positive airway pressure (PAP) ventilation in which a constant level of pressure greater than atmospheric pressure is continuously applied to the upper respiratory tract of a person. The ap ...
to diagnose mild ARDS. Note that the 2012 "Berlin criteria" are a modification of the prior 1994 consensus conference definitions (see ''
history History (derived ) is the systematic study and the documentation of the human activity. The time period of event before the History of writing#Inventions of writing, invention of writing systems is considered prehistory. "History" is an umbr ...
'').


Medical imaging

Radiologic imaging has long been a criterion for diagnosis of ARDS. Original definitions of ARDS specified that correlative
chest X-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
findings were required for diagnosis, the diagnostic criteria have been expanded over time to accept CT and
ultrasound Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
findings as equally contributory. Generally, radiographic findings of fluid accumulation (pulmonary edema) affecting both lungs and unrelated to increased cardiopulmonary vascular pressure (such as in heart failure) may be suggestive of ARDS. Ultrasound findings suggestive of ARDS include the following: * Anterior subpleural consolidations * Absence or reduction of lung sliding * "Spared areas" of normal parenchyma *
Pleura The pulmonary pleurae (''sing.'' pleura) are the two opposing layers of serous membrane overlying the lungs and the inside of the surrounding chest walls. The inner pleura, called the visceral pleura, covers the surface of each lung and dips bet ...
l line abnormalities (irregular thickened fragmented pleural line) * Nonhomogeneous distribution of B-lines (a characteristic ultrasound finding suggestive of fluid accumulation in the lungs)


Treatment

Acute respiratory distress syndrome is usually treated with
mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air ...
in the intensive care unit (ICU). Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the
airway The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...
(endotracheal intubation), or by
tracheostomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision (cut) on the anterior aspect (front) of the neck and opening a direct airway through an incision in the Vertebrate trachea, trache ...
when prolonged ventilation (≥2 weeks) is necessary. The role of
non-invasive ventilation Non-invasive ventilation (NIV) is the use of breathing support administered through a face mask, nasal mask, or a helmet. Air, usually with added oxygen, is given through the mask under positive pressure; generally the amount of pressure is alter ...
is limited to the very early period of the disease or to prevent worsening respiratory distress in individuals with
atypical pneumonia Atypical pneumonia, also known as walking pneumonia, is any type of pneumonia not caused by one of the pathogens most commonly associated with the disease. Its clinical presentation contrasts to that of "typical" pneumonia. A variety of microorgan ...
s, lung bruising, or major surgery patients, who are at risk of developing ARDS. Treatment of the underlying cause is crucial. Appropriate
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
therapy is started as soon as
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups.Tyl ...
results are available, or if
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
is suspected (whichever is earlier).
Empirical therapy Empiric therapy or empirical therapy is medical treatment or therapy based on experience and, more specifically, therapy begun on the basis of a clinical "educated guess" in the absence of complete or perfect information. Thus it is applied before ...
may be appropriate if local microbiological surveillance is efficient. Where possible the origin of the infection is removed. When
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
is diagnosed, appropriate local
protocols Protocol may refer to: Sociology and politics * Protocol (politics), a formal agreement between nation states * Protocol (diplomacy), the etiquette of diplomacy and affairs of state * Etiquette, a code of personal behavior Science and technology ...
are followed.


Mechanical ventilation

The overall goal of mechanical ventilation is to maintain acceptable gas exchange to meet the body's metabolic demands and to minimize adverse effects in its application. The parameters PEEP (positive end-expiratory pressure, to keep alveoli open), mean airway pressure (to promote recruitment (opening) of easily collapsible alveoli and predictor of hemodynamic effects), and
plateau pressure Plateau pressure (PPLAT) is the pressure applied to small airways and Pulmonary alveolus, alveoli during positive-pressure mechanical ventilation. It is measured during an inspiratory pause on the mechanical ventilator.Moon, Richard and Enrico Camp ...
(best predictor of alveolar overdistention) are used. Previously, mechanical ventilation aimed to achieve tidal volumes (''V''t) of 12–15 ml/kg (where the weight is
ideal body weight Human body weight is a person's Mass versus weight, mass or weight. Strictly speaking, body weight is the measurement of weight without items located on the person. Practically though, body weight may be measured with clothes on, but without shoe ...
rather than actual weight). Recent studies have shown that high tidal volumes can overstretch alveoli resulting in
volutrauma Barotrauma is physical damage to body tissues caused by a difference in pressure between a gas space inside, or contact with, the body and the surrounding gas or liquid. The initial damage is usually due to over-stretching the tissues in tensio ...
(secondary lung injury). The ARDS Clinical Network, or ARDSNet, completed a clinical trial that showed improved mortality when people with ARDS were ventilated with a tidal volume of 6 ml/kg compared to the traditional 12 ml/kg. Low tidal volumes (''V''t) may cause a permitted rise in blood carbon dioxide levels and collapse of alveoli because of their inherent tendency to increase shunting within the lung. Physiologic dead space cannot change as it is ventilation without perfusion. A shunt is a perfusion without ventilation within a lung region. 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 was a secondary goal, and subsequent analyses of the data from the ARDSNet trial and other experimental data demonstrate that there appears to be no safe upper limit to plateau pressure; regardless of plateau pressure, individuals with ARDS fare better with low tidal volumes.


Airway pressure release ventilation

No particular ventilator mode is known to improve mortality in acute respiratory distress syndrome (ARDS). Some practitioners favor
airway pressure release ventilation Airway pressure release ventilation (APRV) is a pressure control mode of mechanical ventilation that utilizes an inverse ratio ventilation strategy. APRV is an applied continuous positive airway pressure (CPAP) that at a set timed interval rele ...
when treating ARDS. Well documented advantages to APRV ventilation include decreased airway pressures, decreased
minute ventilation Minute ventilation (or respiratory minute volume or minute volume) is the volume of gas inhaled (inhaled minute volume) or exhaled (exhaled minute volume) from a person's lungs per minute. It is an important parameter in respiratory medicine due ...
, 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 kidney perfusion. A patient with ARDS, on average, spends between 8 and 11 days on a mechanical ventilator; APRV may reduce this time significantly and thus may conserve valuable resources.


Positive end-expiratory pressure

Positive end-expiratory pressure Positive end-expiratory pressure (PEEP) is the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration. The two types of PEEP are extrinsic PEEP (PEEP applied by ...
(PEEP) is used in mechanically ventilated people with ARDS to improve oxygenation. In ARDS, three populations of alveoli can be distinguished. There are normal alveoli that 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 alveoli represent a continuous population, some of which can be recruited with minimal PEEP, and others can only be recruited with high levels of PEEP. An additional complication is that some 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. PEEP can be harmful; high PEEP necessarily increases mean airway pressure and alveolar pressure, which can damage normal alveoli by overdistension resulting in DAD. A compromise between the beneficial and adverse effects of PEEP is inevitable. The 'best PEEP' used to be defined as 'some' cm above the lower inflection point (LIP) in the sigmoidal 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 alveoliand, more importantly, the overdistension of aerated unitsoccur 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 new ventilators can automatically plot a pressure-volume curve. PEEP may also be set empirically. Some authors suggest performing a 'recruiting maneuver'a short time at a very high continuous positive airway pressure, such as 50 cm (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 Pa or peripheral blood oxygen saturation during a step-down trial. A large randomized controlled trial of patients with ARDS found that lung recruitment maneuvers and PEEP titration was associated with high rates of barotrauma and pneumothorax and increased mortality. Intrinsic PEEP (iPEEP) or auto-PEEPfirst described by John Marini of St. Paul Regions Hospitalis a potentially unrecognized contributor to PEEP in intubated individuals. When ventilating at high frequencies, its contribution can be substantial, particularly in people with obstructive lung disease such as
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...
or
chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
(COPD). iPEEP has been measured in very few formal studies on ventilation in ARDS, and its contribution is largely unknown. Its measurement is recommended in the treatment of people who have ARDS, especially when using high-frequency (oscillatory/jet) ventilation.


Prone position

The position 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 is the collapse or closure of a lung resulting in reduced or absent gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the alveoli are deflated down to little or no volume, as distinct ...
and improving perfusion. If this is done early in the treatment of severe ARDS, it confers a mortality benefit of 26% compared to supine ventilation. However, attention should be paid to avoid the
SIDS Sudden infant death syndrome (SIDS) is the sudden unexplained death of a child of less than one year of age. Diagnosis requires that the death remain unexplained even after a thorough autopsy and detailed death scene investigation. SIDS usual ...
in the management of the respiratory distressed infants by continuous careful monitoring of their cardiovascular system.


Fluid management

Several studies have shown that pulmonary function and outcome are better in people with ARDS who lost weight or whose
pulmonary wedge pressure The pulmonary wedge pressure (PWP), also called pulmonary arterial wedge pressure (PAWP), pulmonary capillary wedge pressure (PCWP), pulmonary artery occlusion pressure (PAOP), or cross-sectional pressure, is the pressure measured by wedging a pulm ...
was lowered by
diuresis Diuresis () is increased urination (polyuria) or, in the related word senses more often intended, the physiological process that produces such an increase or the administration of medications to encourage that process. It involves extra urine pro ...
or fluid restriction.


Medications

As of 2019, it is uncertain whether or not treatment with
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s improves overall survival. Corticosteroids may increase the number of ventilator-free days during the first 28 days of hospitalization. One study found that dexamethasone may help. The combination of hydrocortisone, ascorbic acid, and thiamine also requires further study as of 2018. Inhaled
nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...
(NO) selectively widens the lung's arteries which allows for more blood flow to open alveoli for
gas exchange Gas exchange is the physical process by which gases move passively by Diffusion#Diffusion vs. bulk flow, diffusion across a surface. For example, this surface might be the air/water interface of a water body, the surface of a gas bubble in a liqui ...
. Despite evidence of increased oxygenation status, there is no evidence that inhaled nitric oxide decreases morbidity and mortality in people with ARDS. Furthermore, nitric oxide may cause kidney damage and is not recommended as therapy for ARDS regardless of severity. Alvelestat (AZD 9668) had been quoted according to one review article.


Extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support (ECLS), is an extracorporeal technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequat ...
(ECMO) is mechanically applied prolonged cardiopulmonary support. There are two types of ECMO: Venovenous which provides respiratory support and venoarterial which provides respiratory and hemodynamic support. People with ARDS who do not require cardiac support typically undergo venovenous ECMO. Multiple studies have shown the effectiveness of ECMO in acute respiratory failure. Specifically, the CESAR (Conventional ventilatory support versus Extracorporeal membrane oxygenation for Severe Acute Respiratory failure) trial demonstrated that a group referred to an ECMO center demonstrated significantly increased survival compared to conventional management (63% to 47%).


Ineffective treatments

As of 2019, there is no evidence showing that treatments with exogenous
surfactant Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...
s,
statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low- ...
s,
beta-blockers Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...
or
n-acetylcysteine Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...
decreases early mortality, late all-cause mortality, duration of mechanical ventilation, or number of ventilator-free days.


Prognosis

The overall prognosis of ARDS is poor, with mortality rates of approximately 40%. Exercise limitation, physical and psychological sequelae, decreased physical quality of life, and increased costs and use of health care services are important sequelae of ARDS.


Epidemiology

The annual rate of ARDS is generally 13–23 people per 100,000 in the general population. It is more common in people who are mechanically ventilated with acute lung injury (ALI) occurring in 16% of ventilated people. Rates increased in 2020 due to
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
, with some cases also appearing similar to
HAPE High-altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema that occurs in otherwise healthy people at altitudes typically above . However, cases have also been reported between in more vulnerable subjects. ...
. Worldwide, severe sepsis is the most common trigger causing ARDS. Other triggers include mechanical ventilation, sepsis, pneumonia, Gilchrist's disease, drowning, circulatory shock, aspiration,
trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...
especially
pulmonary contusion A pulmonary contusion, also known as lung contusion, is a bruise 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, pot ...
major surgery, massive
blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
s,
smoke inhalation Smoke inhalation is the breathing in of harmful fumes (produced as by-products of combusting substances) through the respiratory tract. This can cause smoke inhalation injury (subtype of acute inhalation injury) which is damage to the respirator ...
, drug reaction or overdose,
fat emboli Fat embolism syndrome occurs when fat enters the blood stream (fat embolism) and results in symptoms. Symptoms generally begin within a day. This may include a petechial rash, decreased level of consciousness, and shortness of breath. Other sympto ...
and reperfusion pulmonary edema after
lung transplantation Lung transplantation, or pulmonary transplantation, is a surgical procedure in which one or both lungs are replaced by lungs from a donor. Donor lungs can be retrieved from a living or deceased donor. A living donor can only donate one lung lobe. ...
or pulmonary embolectomy. However, the majority of patients with all these conditions mentioned do not develop ARDS. It is unclear why some people with the mentioned factors above do not develop ARDS and others do. Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients and may be either causes or complications of ARDS. Alcohol excess appears to increase the risk of ARDS. Diabetes was originally thought to decrease the risk of ARDS, but this has shown to be due to an increase in the risk of pulmonary edema. Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation.


History

Acute respiratory distress syndrome was first described in 1967 by Ashbaugh ''et al.'' Initially there was no clearly established definition, which resulted in controversy regarding the incidence and death of ARDS. In 1988, an expanded definition was proposed, which quantified physiologic respiratory impairment.


1994 American-European Consensus Conference

In 1994, a new definition was recommended by the American-European Consensus Conference Committee which recognized the variability in severity of pulmonary injury. The definition required the following criteria to be met: * acute onset, persistent dyspnea * bilateral infiltrates on chest radiograph consistent with pulmonary edema * hypoxemia, defined as Pa:Fi < 200 mmHg (26.7 kPa) * absence of left atrial (LA) hypertension **
pulmonary artery wedge pressure The pulmonary wedge pressure (PWP), also called pulmonary arterial wedge pressure (PAWP), pulmonary capillary wedge pressure (PCWP), pulmonary artery occlusion pressure (PAOP), or cross-sectional pressure, is the pressure measured by wedging a pulm ...
< 18 mmHg (obtained by
pulmonary artery catheter A pulmonary artery catheter (PAC), also known as a Swan-Ganz catheter or right heart catheter, is a balloon-tipped catheter that is inserted into a pulmonary artery in a procedure known as pulmonary artery catheterization or right heart cathet ...
ization) ** if no measured LA pressure available, there must be no other clinical evidence to suggest elevated left heart pressure. If Pa:Fi < 300 mmHg (40 kPa), then the definitions recommended a classification as "acute lung injury" (ALI). Note that according to these criteria,
arterial blood gas An arterial blood gas (ABG) test, or arterial blood gas analysis (ABGA) measures the amounts of arterial gases, such as oxygen and carbon dioxide. An ABG test requires that a small volume of blood be drawn from the radial artery with a syringe an ...
analysis and
chest X-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
were required for formal diagnosis. Limitations of these definitions include lack of precise definition of acuity, nonspecific imaging criteria, lack of precise definition of hypoxemia with regards to PEEP (affects arterial oxygen partial pressure), arbitrary Pa thresholds without systematic data.


2012 Berlin definition

In 2012, the Berlin Definition of ARDS was devised by the European Society of Intensive Care Medicine, and was endorsed by the
American Thoracic Society The American Thoracic Society (ATS) is a nonprofit organization focused on improving care for pulmonary diseases, critical illnesses and sleep-related breathing disorders. It was established in 1905 as the American Sanatorium Association, and ch ...
and the
Society of Critical Care Medicine The Society of Critical Care Medicine (SCCM) is the largest non-profit medical organization in the practice of critical care. SCCM was established in 1970 and is an independently incorporated, international, educational and scientific society base ...
. These recommendations were an effort to both update classification criteria in order to improve clinical usefulness and to clarify terminology. Notably, the Berlin guidelines discourage the use of the term "acute lung injury" or ALI, as the term was commonly being misused to characterize a less severe degree of lung injury. Instead, the committee proposes a classification of ARDS severity as mild, moderate, or severe according to arterial oxygen saturation. The Berlin definitions represent the current international consensus guidelines for both clinical and research classification of ARDS.


Terminology

ARDS is the severe form of acute lung injury (ALI), and of
transfusion-related acute lung injury Transfusion-related acute lung injury (TRALI) is the serious complication of transfusion of blood products that is characterized by the rapid onset of excess fluid in the lungs. It can cause dangerous drops in the supply of oxygen to body tissu ...
(TRALI), though there are other causes. The Berlin definition included ALI as a mild form of ARDS. However, the criteria for the diagnosis of ARDS in the Berlin definition excludes many children, and a new definition for children was termed ''pediatric'' acute respiratory distress syndrome (PARDS); this is known as the PALICC definition (2015).


Research directions

There is ongoing research on the treatment of ARDS by interferon (IFN) beta-1a to aid in preventing leakage of vascular beds. Traumakine (FP-1201-lyo) is a recombinant human IFN beta-1a drug, developed by the Finnish company Faron Pharmaceuticals, which is undergoing international phase-III clinical trials after an open-label, early-phase trial showed an 81% reduction-in-odds of 28-day mortality in ICU patients with ARDS. The drug is known to function by enhancing lung
CD73 5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 (cluster of differentiation 73), is an enzyme that in humans is encoded by the ''NT5E'' gene. CD73 commonly serves to convert AMP to adenosine. Transcription factor bindin ...
expression and increasing production of anti-inflammatory adenosine, such that vascular leaking and escalation of inflammation are reduced.
Aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
has been studied in those who are at high risk and was not found to be useful. An intravenous
ascorbic acid Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
treatment was tested in the 2019 RCT, in people with ARDS due to sepsis and there was no change in primary endpoints.


See also

*
Respiratory monitoring Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air i ...


References


Further reading

* * * * *


External links


ARDSNet
€”the NIH / NHLBI ARDS Network
ARDS Support Center
€”information for patients with ARDS {{DEFAULTSORT:Acute Respiratory Distress Syndrome Causes of death Intensive care medicine Respiratory diseases principally affecting the interstitium Respiratory physiology Syndromes affecting the respiratory system