View source for Acute respiratory distress syndrome natural history, complications, and prognosis

__NOTOC__
{{Acute respiratory distress syndrome}}
{{CMG}}; {{AE}} {{BShaller}}

==Overview==
If left untreated, 70% of patients with ARDS may progress to [[mortality]]. Common complications to ARDS include [[weakness]], impaired [[spirometry|lung function]], and [[brain death]]. Prognosis for patients with ARDS is generally poor and varies based on the severity of illness, the precipitating insult, and medical comorbidities.

==Natural History==
The natural history of ARDS is hallmarked by three histopathological phases—exudative, proliferative, and fibrotic phase—each correlated to distinctive clinical manifestations.<ref>Ware, Lorraine B. “Autopsy in ARDS: Insights into Natural History.” The Lancet. Respiratory Medicine 1, no. 5 (July 2013): 352–54. doi:10.1016/S2213-2600(13)70093-6.</ref>

===Exudative Phase===
The exudative phase typically encompasses the first 5 to 7 days of illness after exposure to one or more precipitation factors. Histopathologically, loss of integrity of the alveolar barrier results in influx of proteinaceous fluid into the air place and formation of hyaline membrane. [[Pulmonary edema]] and [[atelectasis]] with reduced [[pulmonary compliance]] ensue, leading to the development of [[pulmonary shunt]] and [[hypoxemia]]. In this phase, patients experience respiratory symptoms including [[dyspnea]], [[tachypnea]], and [[Labored breathing|increased work of breathing]] that eventually result in [[respiratory failure]] requiring ventilator support. If left untreated, approximately 70% of patients with ARDS may progress to [[mortality]].<ref>National Heart and Lung Institute. Task Force on Research in Respiratory Diseases, and National Heart and Lung Institute. Lung Program. Respiratory Diseases; Task Force Report on Problems, Research Approaches, Needs. The Lung Program, National Heart and Lung Institute. [Bethesda, Md., U.S. Dept. of Health, Education, and Welfare, National Institutes of Health] for sale by the Supt. of Docs., U.S. Govt. Print. Off., Washington, 1972. http://archive.org/details/respiratorydisea00nati.</ref> Among non-survivors, approximately 50% patients die within a week of the onset with exudative change as the predominant histopathological feature.<ref>Thille, Arnaud W., Andrés Esteban, Pilar Fernández-Segoviano, José-María Rodriguez, José-Antonio Aramburu, Patricio Vargas-Errázuriz, Ana Martín-Pellicer, José A. Lorente, and Fernando Frutos-Vivar. “Chronology of Histological Lesions in Acute Respiratory Distress Syndrome with Diffuse Alveolar Damage: A Prospective Cohort Study of Clinical Autopsies.” The Lancet. Respiratory Medicine 1, no. 5 (July 2013): 395–401. doi:10.1016/S2213-2600(13)70053-5.</ref>

===Proliferative Phase===
The proliferative phase generally lasts from day 7 to day 21. Histopathologically, reparative processes take place in the injured alveoli, including organization of exudates, a shift to [[lymphocyte]]-predominant infiltrates, and proliferation of type II [[pneumocyte]]s. In this phase, patients may recover from acute respiratory distress despite the persistence of residual symptoms. Patients who do not recover during this phase develop progressive lung injury and early changes of [[fibrosis]].

===Fibrotic Phase===
The fibrotic phase occurs 3 to 4 weeks following the initial pulmonary insult. Histopathologically, extensive [[fibrosis]] is prominent in the alveolar interstitium and duct, with disruption of acinar architecture and [[emphysema]]-like changes. The evidence for [[pulmonary fibrosis]] on biopsy is associated with increased [[mortality]].

==Complications==
Complications of ARDS are more likely to develop among patients who do not receive early or adequate treatment.

Common complications include:
* [[Ventilator-associated pneumonia|Ventilator-associated pneumonia (VAP)]]
:* ARDS is complicated by VAP in approximately 37% to 60% of cases.<ref>Delclaux, C., E. Roupie, F. Blot, L. Brochard, F. Lemaire, and C. Brun-Buisson. “Lower Respiratory Tract Colonization and Infection during Severe Acute Respiratory Distress Syndrome: Incidence and Diagnosis.” American Journal of Respiratory and Critical Care Medicine 156, no. 4 Pt 1 (October 1997): 1092–98. doi:10.1164/ajrccm.156.4.9701065.</ref><ref>Markowicz, P., M. Wolff, K. Djedaïni, Y. Cohen, J. Chastre, C. Delclaux, J. Merrer, et al. “Multicenter Prospective Study of Ventilator-Associated Pneumonia during Acute Respiratory Distress Syndrome. Incidence, Prognosis, and Risk Factors. ARDS Study Group.” American Journal of Respiratory and Critical Care Medicine 161, no. 6 (June 2000): 1942–48. doi:10.1164/ajrccm.161.6.9909122.</ref><ref>Meduri, G. U., R. C. Reddy, T. Stanley, and F. El-Zeky. “Pneumonia in Acute Respiratory Distress Syndrome. A Prospective Evaluation of Bilateral Bronchoscopic Sampling.” American Journal of Respiratory and Critical Care Medicine 158, no. 3 (September 1998): 870–75. doi:10.1164/ajrccm.158.3.9706112.</ref><ref>Chastre, J., J. L. Trouillet, A. Vuagnat, M. L. Joly-Guillou, H. Clavier, M. C. Dombret, and C. Gibert. “Nosocomial Pneumonia in Patients with Acute Respiratory Distress Syndrome.” American Journal of Respiratory and Critical Care Medicine 157, no. 4 Pt 1 (April 1998): 1165–72. doi:10.1164/ajrccm.157.4.9708057.</ref>
:* [[VAP]] usually develops 5 to 7 days after the initial exposure to the precipitating factor.<ref>Delclaux, C., E. Roupie, F. Blot, L. Brochard, F. Lemaire, and C. Brun-Buisson. “Lower Respiratory Tract Colonization and Infection during Severe Acute Respiratory Distress Syndrome: Incidence and Diagnosis.” American Journal of Respiratory and Critical Care Medicine 156, no. 4 Pt 1 (October 1997): 1092–98. doi:10.1164/ajrccm.156.4.9701065.</ref>
:* The most likely microorganisms of [[VAP]] include non-fermenting [[Gram-negative bacilli]], [[methicillin]]-resistant ''[[Staphylococcus aureus]]'', and ''[[Enterobacteriaceae]]''.<ref>Chastre, J., J. L. Trouillet, A. Vuagnat, M. L. Joly-Guillou, H. Clavier, M. C. Dombret, and C. Gibert. “Nosocomial Pneumonia in Patients with Acute Respiratory Distress Syndrome.” American Journal of Respiratory and Critical Care Medicine 157, no. 4 Pt 1 (April 1998): 1165–72. doi:10.1164/ajrccm.157.4.9708057.</ref>
* [[Barotrauma]] (e.g., [[pneumothorax]], [[pneumomediastinum]], and [[subcutaneous emphysema]])
:* [[Barotrauma]] occurs as a consequence of inappropriate [[positive airway pressure]] in regions with reduced [[pulmonary compliance]] and may complicate ARDS in approximately 10% of cases.<ref>“Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. The Acute Respiratory Distress Syndrome Network.” The New England Journal of Medicine 342, no. 18 (May 4, 2000): 1301–8. doi:10.1056/NEJM200005043421801.</ref><ref>Weg, J. G., A. Anzueto, R. A. Balk, H. P. Wiedemann, E. N. Pattishall, M. A. Schork, and L. A. Wagner. “The Relation of Pneumothorax and Other Air Leaks to Mortality in the Acute Respiratory Distress Syndrome.” The New England Journal of Medicine 338, no. 6 (February 5, 1998): 341–46. doi:10.1056/NEJM199802053380601.</ref><ref>Stewart, T. E., M. O. Meade, D. J. Cook, J. T. Granton, R. V. Hodder, S. E. Lapinsky, C. D. Mazer, et al. “Evaluation of a Ventilation Strategy to Prevent Barotrauma in Patients at High Risk for Acute Respiratory Distress Syndrome. Pressure- and Volume-Limited Ventilation Strategy Group.” The New England Journal of Medicine 338, no. 6 (February 5, 1998): 355–61. doi:10.1056/NEJM199802053380603.</ref>
Other complications include:
*Significant [[weakness]] due to [[muscle atrophy|critical illness myoneuropathy and muscle atrophy]] as a result of long-term immobilization
*Impaired [[Spirometry|lung function]]
*Chronic [[Mechanical ventilation|ventilator dependency]] due to advanced weakness and [[atrophy]] of the [[muscles of respiration]]
*[[Pulmonary fibrosis]] and [[restrictive lung disease]]
*[[Psychiatric illness]], including [[post-traumatic stress disorder]] (PTSD), [[anxiety]], and [[depression]]
*Impaired [[cognition]]
*[[Persistent vegetative state]] or [[brain death]] due to prolonged [[hypoxemia]]

Complications associated with a prolonged ICU stay include:
*[[Nosocomial infection|Secondary or nosocomial infections]] (e.g., [[hospital-acquired pneumonia|ventilator-associated pneumonia]] <nowiki>[</nowiki>VAP<nowiki>]</nowiki> or [[Intravascular device related infections|central line-associated blood stream infection]] <nowiki>[</nowiki>CLABSI<nowiki>]</nowiki>)
*[[Venous thromboembolism|Venous thromboembolic events]] (e.g., [[deep vein thrombosis]] <nowiki>[</nowiki>DVT<nowiki>]</nowiki> or [[pulmonary embolism]] <nowiki>[</nowiki>PE<nowiki>]</nowiki>)
*[[GI bleed|Gastrointestinal bleeding]] (often secondary to [[Stress ulcer|stress ulcers]])
*[[Pressure ulcers]] and poor [[wound healing]]
*[[Muscle atrophy|Muscle wasting]] and [[atrophy]]

==Prognosis==
Prognosis for patients with ARDS is generally poor and varies based on the severity of illness, the precipitating insult, and medical comorbidities:<ref name="pmid11056707">{{cite journal| author=Reynolds HN, McCunn M, Borg U, Habashi N, Cottingham C, Bar-Lavi Y| title=Acute respiratory distress syndrome: estimated incidence and mortality rate in a 5 million-person population base. | journal=Crit Care | year= 1998 | volume= 2 | issue= 1 | pages= 29-34 | pmid=11056707 | doi=10.1186/cc121 | pmc=28999 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11056707  }} </ref><ref name="pmid22797452">{{cite journal| author=ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E et al.| title=Acute respiratory distress syndrome: the Berlin Definition. | journal=JAMA | year= 2012 | volume= 307 | issue= 23 | pages= 2526-33 | pmid=22797452 | doi=10.1001/jama.2012.5669 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797452  }} </ref><ref name="pmid12594312">{{cite journal| author=Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F et al.| title=One-year outcomes in survivors of the acute respiratory distress syndrome. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 8 | pages= 683-93 | pmid=12594312 | doi=10.1056/NEJMoa022450 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12594312  }} </ref><ref name="pmid20384998">{{cite journal| author=Linko R, Suojaranta-Ylinen R, Karlsson S, Ruokonen E, Varpula T, Pettilä V et al.| title=One-year mortality, quality of life and predicted life-time cost-utility in critically ill patients with acute respiratory failure. | journal=Crit Care | year= 2010 | volume= 14 | issue= 2 | pages= R60 | pmid=20384998 | doi=10.1186/cc8957 | pmc=2887181 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20384998  }} </ref><ref name="pmid24435201">{{cite journal| author=Wang CY, Calfee CS, Paul DW, Janz DR, May AK, Zhuo H et al.| title=One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome. | journal=Intensive Care Med | year= 2014 | volume= 40 | issue= 3 | pages= 388-96 | pmid=24435201 | doi=10.1007/s00134-013-3186-3 | pmc=3943651 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24435201  }} </ref><ref name="pmid20507948">{{cite journal| author=Sheu CC, Gong MN, Zhai R, Chen F, Bajwa EK, Clardy PF et al.| title=Clinical characteristics and outcomes of sepsis-related vs non-sepsis-related ARDS. | journal=Chest | year= 2010 | volume= 138 | issue= 3 | pages= 559-67 | pmid=20507948 | doi=10.1378/chest.09-2933 | pmc=2940067 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20507948  }} </ref>
* The 90-day morality rates for mild, moderate, and severe ARDS are 27%, 32%, and 45%, respectively.
* The 1-year mortality rate for patients with ARDS who survive to hospital discharge varies widely and is estimated at 11% to over 40%.
* Between 1992 and 1995, in-hospital mortality rate ranges from 36% to 52%.
* ARDS among [[trauma]] patients have a lower mortality as compared with [[sepsis]] patients.

==References==
{{reflist|2}}

[[Category:Pulmonology]]