(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 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 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 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 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-peep—first described by john marini of st. paul regions hospital—is 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 or chronic obstructive pulmonary disease (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 main article: proning 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 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 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 was lowered by diuresis or fluid restriction. medications as of 2019, it is uncertain whether or not treatment with corticosteroids 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 (no) selectively widens the lung's arteries which allows for more blood flow to open alveoli for gas exchange. 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 (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 surfactants, statins, beta-blockers or n-acetylcysteine 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, with some cases also appearing similar to hape. 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—especially pulmonary contusion—major surgery, massive blood transfusions, smoke inhalation, drug reaction or overdose, fat emboli and reperfusion pulmonary edema after lung transplantation 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 pao2:fio2 < 200 mmhg (26.7 kpa) absence of left atrial (la) hypertension pulmonary artery wedge pressure < 18 mmhg (obtained by pulmonary artery catheterization) if no measured la pressure available, there must be no other clinical evidence to suggest elevated left heart pressure. if pao2:fio2 < 300 mmhg (40 kpa), then the definitions recommended a classification as "acute lung injury" (ali). note that according to these criteria, arterial blood gas analysis and chest x-ray 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 pao2 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 and the society of critical care medicine. 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 (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 expression and increasing production of anti-inflammatory adenosine, such that vascular leaking and escalation of inflammation are reduced. aspirin has been studied in those who are at high risk and was not found to be useful. an intravenous ascorbic acid treatment was tested in the 2019 rct, in people with ards due to sepsis and there was no change in primary endpoints.