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


==Overview==
==Overview==
The majority of medical therapies for ARDS are aimed at treating its underlying cause (e.g., [[antimicrobials]] for [[infection]]).
==Medical Therapy==
==Medical Therapy==
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]]s, pulmonary contusion, major surgery patients).
Although patients with ARDS often require aggressive medical therapies aimed at treating their [[Acute respiratory distress syndrome causes|underlying illness]], there are few medical therapies (beyond [[Acute respiratory distress syndrome mechanical ventilation therapy|mechanical ventilation and other strategies to improve oxygenation]]) that address the physiologic derangements of ARDS itself.
 
Treatment of the underlying cause is imperative, as it tends to maintain the ARDS picture.
 
Appropriate [[antibiotic]] therapy must be administered as soon as [[microbiological culture]] results are available. Empirical 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.


===Fluid management===
===Fluid management===
Several studies have shown that pulmonary function and outcome are better in patients that lost weight or wedge pressure was lowered by [[diuresis]] or fluid restriction.
Removal of excess fluids via [[diuresis]] or [[renal replacement therapy]] (typically continuous renal replacement therapy or [[hemodialysis]]) in patients with concomitant [[Hypervolemia|volume overload]] due to [[heart failure]] or [[renal dysfunction]] is recommended, however, these interventions are of little or no benefit in patients who are not volume-overloaded (i.e., euvolemic).


===Corticosteroids===
===Corticosteroids===
Patients with ARDS do not benefit from high-dose corticosteroids. Meduri et al however did find significant improvement using modest doses. This is probably because of a suppression of ongoing inflammation during the fibroproliferative phase of ARDS. The initial regimen consists of [[methylprednisolone]] 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. In the absence of results steroids can be discontinued.<ref name=Meduri-ARDS>{{cite journal | author = Meduri G, Tolley E, Chrousos G, Stentz F | title = Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. | journal = Am J Respir Crit Care Med | volume = 165 | issue = 7 | pages = 983-91 | year = 2002 | id = PMID 11934726}}</ref>
While patients with [[Adrenal insufficiency|adrenal insufficiency]] and ARDS should receive [[Adrenal insufficiency medical therapy|stress-dosed glucocorticoid replacement therapy]], [[Corticosteroid|glucocorticoids]] by themselves have not been demonstrated to improve survival and may increase mortality in ARDS. The lack of benefit of glucocorticoid therapy for ARDS was demonstrated in the LaSRS (pronounced ''Lazarus'') Trial (conducted by the '''NIH-NHLBI ARDS Clinical Trials Network''' from 1997 to 2003) – a multicenter [[Randomized controlled trial|randomized, controlled trial]] comparing [[Methylprednisolone (injection)|methylprednisolone]] versus [[placebo]] for 21 days in patients with [[Acute respiratory distress syndrome diagnostic criteria|moderate-to-severe ARDS]]. Patients in the methylprednisolone arm experienced more [[Mechanical ventilation|ventilator]]-free, [[shock]]-free, and [[ICU]]-free days by follow-up day 28; however, no survival benefit was observed and a significantly higher [[mortality rate]] was observed at 60 and 180 days in patients who received methylprednisolone more than 14 days after the onset of ARDS.<ref name="pmid16625008">{{cite journal| author=Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R et al.| title=Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. | journal=N Engl J Med | year= 2006 | volume= 354 | issue= 16 | pages= 1671-84 | pmid=16625008 | doi=10.1056/NEJMoa051693 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16625008  }} </ref>


The recent NIH-sponsored ARDSnet LAZARUS study of corticosteroids for ARDS demonstrated that they are not efficacious in ARDS.
=== Inhaled Pulmonary Vasodilators ===
 
'''Inhaled pulmonary vasodilators''' (medications that [[dilate]] the [[vessels]] of [[Pulmonary circulation|pulmonary arterial circulation]]) have been used to improve [[hypoxemia]] by reversing ventilation/perfusion (V/Q) mismatching, however, studies of inhaled nitric oxide (iNO) and [[epoprostenol|inhaled prostacyclin]] have not demonstrated a survival benefit to these therapies.<ref name="pmid15069048">{{cite journal| author=Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K et al.| title=Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. | journal=JAMA | year= 2004 | volume= 291 | issue= 13 | pages= 1603-9 | pmid=15069048 | doi=10.1001/jama.291.13.1603 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15069048  }} </ref><ref name="pmid24132038">{{cite journal| author=Adhikari NK, Dellinger RP, Lundin S, Payen D, Vallet B, Gerlach H et al.| title=Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis. | journal=Crit Care Med | year= 2014 | volume= 42 | issue= 2 | pages= 404-12 | pmid=24132038 | doi=10.1097/CCM.0b013e3182a27909 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24132038  }} </ref><ref name="pmid8630585">{{cite journal| author=Walmrath D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W| title=Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. | journal=Am J Respir Crit Care Med | year= 1996 | volume= 153 | issue= 3 | pages= 991-6 | pmid=8630585 | doi=10.1164/ajrccm.153.3.8630585 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8630585  }} </ref><ref name="pmid8970353">{{cite journal| author=Zwissler B, Kemming G, Habler O, Kleen M, Merkel M, Haller M et al.| title=Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. | journal=Am J Respir Crit Care Med | year= 1996 | volume= 154 | issue= 6 Pt 1 | pages= 1671-7 | pmid=8970353 | doi=10.1164/ajrccm.154.6.8970353 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8970353  }} </ref> It is important to monitor the [[platelet count]] when initiating treatment with inhaled prostacyclin due to the low risk of [[thrombocytopenia]].
===Nitric oxide===
Inhaled [[nitric oxide]] (NO) potentially acts as selective pulmonary vasodilator. Rapid binding to [[hemoglobin]] 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 [[Randomized controlled trial|controlled clinical trial]] has shown a significant mortality benefit of exogenous surfactant in ARDS.


==References==
==References==
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Latest revision as of 03:48, 20 July 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Brian Shaller, M.D. [2]

Overview

The majority of medical therapies for ARDS are aimed at treating its underlying cause (e.g., antimicrobials for infection).

Medical Therapy

Although patients with ARDS often require aggressive medical therapies aimed at treating their underlying illness, there are few medical therapies (beyond mechanical ventilation and other strategies to improve oxygenation) that address the physiologic derangements of ARDS itself.

Fluid management

Removal of excess fluids via diuresis or renal replacement therapy (typically continuous renal replacement therapy or hemodialysis) in patients with concomitant volume overload due to heart failure or renal dysfunction is recommended, however, these interventions are of little or no benefit in patients who are not volume-overloaded (i.e., euvolemic).

Corticosteroids

While patients with adrenal insufficiency and ARDS should receive stress-dosed glucocorticoid replacement therapy, glucocorticoids by themselves have not been demonstrated to improve survival and may increase mortality in ARDS. The lack of benefit of glucocorticoid therapy for ARDS was demonstrated in the LaSRS (pronounced Lazarus) Trial (conducted by the NIH-NHLBI ARDS Clinical Trials Network from 1997 to 2003) – a multicenter randomized, controlled trial comparing methylprednisolone versus placebo for 21 days in patients with moderate-to-severe ARDS. Patients in the methylprednisolone arm experienced more ventilator-free, shock-free, and ICU-free days by follow-up day 28; however, no survival benefit was observed and a significantly higher mortality rate was observed at 60 and 180 days in patients who received methylprednisolone more than 14 days after the onset of ARDS.[1]

Inhaled Pulmonary Vasodilators

Inhaled pulmonary vasodilators (medications that dilate the vessels of pulmonary arterial circulation) have been used to improve hypoxemia by reversing ventilation/perfusion (V/Q) mismatching, however, studies of inhaled nitric oxide (iNO) and inhaled prostacyclin have not demonstrated a survival benefit to these therapies.[2][3][4][5] It is important to monitor the platelet count when initiating treatment with inhaled prostacyclin due to the low risk of thrombocytopenia.

References

  1. Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R; et al. (2006). "Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome". N Engl J Med. 354 (16): 1671–84. doi:10.1056/NEJMoa051693. PMID 16625008.
  2. Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K; et al. (2004). "Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial". JAMA. 291 (13): 1603–9. doi:10.1001/jama.291.13.1603. PMID 15069048.
  3. Adhikari NK, Dellinger RP, Lundin S, Payen D, Vallet B, Gerlach H; et al. (2014). "Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis". Crit Care Med. 42 (2): 404–12. doi:10.1097/CCM.0b013e3182a27909. PMID 24132038.
  4. Walmrath D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W (1996). "Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome". Am J Respir Crit Care Med. 153 (3): 991–6. doi:10.1164/ajrccm.153.3.8630585. PMID 8630585.
  5. Zwissler B, Kemming G, Habler O, Kleen M, Merkel M, Haller M; et al. (1996). "Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome". Am J Respir Crit Care Med. 154 (6 Pt 1): 1671–7. doi:10.1164/ajrccm.154.6.8970353. PMID 8970353.