Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition caused by infection, injury or other insults that leads to hypoxemia. It is characterized by diffuse alveolar damage and impaired gas exchange. ARDS has a mortality rate ranging from 27-45% depending on severity. Treatment involves lung-protective ventilation with low tidal volumes, conservative fluid management, prone positioning in severe cases, paralysis and consideration of steroids in refractory cases. Refractory ARDS may be treated with extracorporeal membrane oxygenation.

1. 1
Alveolar-capillary
damage
Pulmonary edema+
Proteinemia+
Inflammation
Repair: Reabsorption of
edema and matrix
Fibrosis
Background and Epidemiology
Pathophysiology
ARDS
Anna Sandler
PharmD Candidate, 2023
 Acute respiratory distress syndrome (ARDS): Life-threatening
inflammatory lung process leading to profound hypoxemia
 Common causes: infection (e.g., COVID-19), inhalation injury,
drug overdose, aspiration, mechanical ventilation, sepsis,
drowning
 MINIMAL improvements in mortality and incidence
 Mortality: 27%, 32%, and 45% for mild, moderate, and severe
disease respectively
 Pre-COVID: 10% of all ICU
patients, ~25% of all
mechanically ventilated
patients1
Genetics2 ETOH/Smoking
Virulence
factors
Comorbidities3
ETOH: ethanol,
1: Data obtained from a 2016 international prospective cohort study by Bellani and colleagues involving > 29,000 patients in 50
countries.
2: More than 40 genes have been identified including genes encoding angiotensin-converting enzyme (ACE)-IL-10, TNF, VEGF,
NAMPT, MYLK, NFE2L2
3: E.g., pneumococcal pneumonia post-splenectomy
Socioeconomic
Status
Exudative phase: Innate-cell mediated injury due to release
of proinflammatory cytokines and activation of immune cells
Proliferative phase
Fibrotic phase:
Extensive membrane
damage, delayed
repair
Impaired gas exchange
+ Hypoxemia

2. 2
Test Findings
ABGs  Respiratory alkalosis
 Severe: hypercapnic respiratory acidosis
 Metabolic acidosis: rare, usually 2/2 organ injury
(e.g., AKI)
CXR, CT  Bilateral diffuse alveolar opacities, pleural effusions,
pneumothorax
Other  Routine chemistries reflecting organ injury:
elevated LFTs, AKI, etc.
 ARDS 2/2 infection +/- sepsis: leukocytosis, elevated
lactate
•Mechanical ventilation
Preventative
•Proning and Fluid Restriction
Supportive
•Paralysis, Inhaled Pulmonary Vasodilators, VV ECMO, Steroids
Rescue/Refractory
Diagnosis and Presentation
 Presentation
o Progressively worsening dyspnea and hypoxemia
 Increased effort, cyanosis
o Respiratory exam: bibasilar rales
o Acute confusion
o Diaphoresis
Acute Onset: </= 1 week of insult
Bilateral opacities
PaO2/FIO2 </= 300 mmHg4 Mild: 201- 300
mmHg
Moderate: 101-200
mmHg
Severe: </=100
mmHg
Berlin Definition4 of ARDS
Treatment Overview
FIO2 : Fraction of inspired oxygen, PaO2: Partial pressure of oxygen in arterial blood;
4: The Berlin Definition is now used as part of the diagnostic work-up of ARDS since it was found to have a better predictive
validity for mortality when compared to the original 1994 definition developed by the American European Consensus
Conference.

3. 3
Therapy Pearls Evidence and
Benefits
Mortality
benefit?
LPV Combines low tidal volumes (4-8
mL/kg) and high respiratory rates
Utilization of lower plateau
pressures5
Consider higher levels of PEEP
ARMA trial (2000)
Mortality, increased
no. days w/h
ventilator
Therapy Pearls Evidence and
Benefits
Mortality
benefit?
Proning Optimizes lung
recruitment and lung
perfusion
Shifts fluid to areas with
less alveoli
16 hours proning/8 hours
off
PROSEVA trial
(2013):
28 and 90-day
mortality benefits
in severe ARDS:
PaO2/FIO2 < 150
Conservative
fluid
management
No consensus on specific
fluid restriction goals.
Limit IV fluids. Employ
diuresis.
FACTT trial (2006)
Enhanced
oxygenation, fewer
days on mechanical
ventilation, fewer
days in the ICU
Semler et al.
(2016)6
potential
mortality benefits
 Fluid overload:
deleterious effects
in ARDS
 No specific fluids
recommended for
ARDS
Treatment: Lung-protective ventilation
Preventative
 Lung-protective ventilation (LPV)
o Prevent volutrama and barotrauma
 Disruption of pulmonary endo- and
epithelium inflammation
5: Pressure applied by the ventilator to the small airways and alveoli
6: Semler and colleagues reveal a potential mortality benefit of conservative fluid management in a retrospective analysis,
specifically in patients with a central venous pressure of 8 mm Hg or less.
Treatment: Proning and Fluids
Supportive

4. 4
Therapy Pearls Evidence and Benefits Mortality
benefit?
NM Block Help promote ventilator
synchrony and reduce oxygen
consumptions
Agents:
 Cisatracurium
 Rocuronium
 Vecuronium
 Pancuronium
ADRs: Muscle weakness
Sedation required before and
during paralysis
ACURASYS trial (2010)
Improved 90-day survival in severe ARDS
treated early with cisatracurium:
PaO2/FIO2 < 150
ROSE trial (2019)
Stopped early, unable to show mortality
benefits
Overall: Improve work of breathing and
ventilator dyssynchrony
Therapy Pearls Mortality benefit?
Inhaled nitric
oxide
Modest improvement in oxygenation
Potential harms: Renal impairment
Therapy Pearls Evidence and Benefits Mortality benefit?
Steroids Recommended for persistent or refractory
moderate-severe ARDS
( PaO2/FIO2 < 200)
despite initial management early in the
disease course (within 14 days onset)
Agents:
Methylprednisolone 1mg/kg/day for 21-28
days followed by a taper
Dexamethasone 20 mg IV once daily for five
days, then 10 mg once daily for five days
ADRs: Hyperglycemia, poor wound healing,
insomnia, GI upset
DEXA-ARDS (2020):
Increased ventilator-
free days and
decreased mortality in
the dexamethasone
group
Treatment: Glucocorticoids
Treatment: Inhaled Vasodilators
Treatment: Paralysis
Rescue/Refractory

5. 5
Therapy Pearls/Benefits Mortality Benefit?
VV ECMO Improves oxygenation
Lung “rest”
Referral should be considered early in disease
course
Exclusion criteria:
Older age, obesity, active cancer, prolonged
mechanical ventilation, unwitnessed cardiac
arrest
Ineffective or Harmful Therapies
Treatment: VV ECMO
 Venovenous Extracorporeal membrane oxygenation (VVECMO)
o Salvage therapy in refractory ARDS
o PaO2/FIO2 < 100, Berlin consensus suggests if PaO2/FIO2 < 70
 Pump delivers venous blood to
one side of the oxygenator
membrane
 From the blender, fresh gas
(sweep gas) is passed into the
other side of the oxygenator
membrane
 Gas exchange occurs
 Blood is returned to the patient
 Anti-oxidants: N-acetylcysteine, glutamine, vitamin E, beta carotene, omega-3 fatty acids
 IV prostaglandin E1
 Ibuprofen
 Statins
 Short-acting beta-2 agonists

6. 6
1. Welker C, Huang J, Gil IJN, Ramakrishna H. 2021 Acute Respiratory Distress Syndrome Update, With
Coronavirus Disease 2019 Focus. Journal of Cardiothoracic and Vascular Anesthesia. 2022;36(4):1188-1195.
doi:10.1053/j.jvca.2021.02.053
2. Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. Drazen JM, ed. N Engl J Med.
2017;377(6):562-572. doi:10.1056/NEJMra1608077
3. Diamond M, Peniston HL, Sanghavi D, Mahapatra S, Doerr C. Acute Respiratory Distress Syndrome (Nursing).
In: StatPearls. StatPearls Publishing; 2022. Accessed July 25, 2022.
http://www.ncbi.nlm.nih.gov/books/NBK568726/
4. Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA. 2012;307(23).
doi:10.1001/jama.2012.5669
5. Comparison of Two Fluid-Management Strategies in Acute Lung Injury. N Engl J Med. 2006;354(24):2564-
2575. doi:10.1056/NEJMoa062200
6. Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress
syndrome: a multicentre, randomised controlled trial. The Lancet Respiratory Medicine. 2020;8(3):267-276.
doi:10.1016/S2213-2600(19)30417-5
7. Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute
Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016;315(8):788-800.
doi:10.1001/jama.2016.0291
8. Mendes R de S, Pelosi P, Schultz MJ, Rocco PRM, Silva PL. Fluids in ARDS: more pros than cons. ICMx.
2020;8(S1):32. doi:10.1186/s40635-020-00319-x
9. Semler MW, Wheeler AP, Thompson BT, et al. Impact of Initial Central Venous Pressure on Outcomes of
Conservative Versus Liberal Fluid Management in Acute Respiratory Distress Syndrome. Crit Care Med.
2016;44(4):782-789. doi:10.1097/CCM.0000000000001555
10. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular Blockers in Early Acute Respiratory Distress
Syndrome. N Engl J Med. 2010;363(12):1107-1116. doi:10.1056/NEJMoa1005372
11. Guérin C, Reignier J, Richard JC, et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. N
Engl J Med. 2013;368(23):2159-2168. doi:10.1056/NEJMoa1214103
12. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and
the Acute Respiratory Distress Syndrome. N Engl J Med. 2000;342(18):1301-1308.
doi:10.1056/NEJM200005043421801
Picture Links
https://www.medicalnewstoday.com/articles/266682
https://www.uptodate.com/contents/acute-respiratory-distress-syndrome-clinical-features-diagnosis-and-
complications-in-adults/print
https://www.cureus.com/articles/31162-coronavirus-covid-19-fulminant-myopericarditis-and-acute-respiratory-
distress-syndrome-ards-in-a-middle-aged-male-patient
https://breathe.ersjournals.com/content/9/2/90.figures-only
https://www.healthline.com/health/lung-cancer/prone-position
https://consultqd.clevelandclinic.org/venovenous-extracorporeal-membrane-oxygenation-for-lung-failure/
http://clipart-library.com/danger-sign.html
References