Acute Respiratory Distress

Syndrome (ARDS)
Maggie Kline, PharmD
PGY1 Pharmacy Resident
Objectives

Define ARDS

Discuss efficacy of pharmacological treatments for ARDS

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Normal Lung Function

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Normal Lung
Epithelium

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Ventilator Terminology Basics
 PaO2 = partial pressure of oxygen in arterial blood (normal 75-100 mmHg, 21%
FiO2)
 FiO2 = Fraction of inspired air that is oxygen (RA is 21%)
 Often started at 100% and weaned down; Increased exposure to high FiO2 
increased free radical damage  fibrosis
 PEEP = positive end airway pressure = pressure in lungs at the end of expiration
that keeps alveoli open, improving gas exchange (normal 5-10 cm H20); potential
AE of high PEEP include barotrauma and decreased venous return

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Image: https://healthjade.net/peak-inspiratory-pressure/
 Definition of ARDS
Berlin Definition (2012)
Within 7 day of known insult or new or worsening respiratory
symptoms
Combination of acute hypoxemia (PaO2/FiO2 <=300 mmHg) in a
ventilated patient with PEEP >5 cmH20
⎻Mild 201 to 300
⎻Moderate 101 to 200
⎻Severe <=100
Bilateral opacities not explained fully by HF or fluid overload
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Ann Intensive Care. 2019;9(1):69.
Causes of ARDS

Pulmonary
infection or Sepsis Trauma
aspiration

Massive Drug
Drowning
transfusion overdose

Inhalation
Pancreatitis
injury
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 ARDS Pathophysiology – Exudative Phase

Lancet. 2016;388(10058):2416-2430.
 ARDS Pathophysiology – Proliferative and Fibrotic Phases

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Lancet. 2016;388(10058):2416-2430.
 Epidemiology
 LUNG SAFE study:
 29,000 patients in 50 countries
 ARDS accounted for 10% of ICU admissions and 23% of ventilated patients
 Hospital mortality increased with severity of ARDS and was 40-45% overall
 Mild ARDS may be under-identified

 ARDS can impact quality of life up to 5 years later

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Ann Intensive Care. 2019;9(1):69.
Goals of ARDS Treatment

Treat the
underlying
cause

Prevent
Provide
harm due
supportive
to
care
treatment

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 Suggested ARDS
Treatment Guidelines
Due to the complexities
involved, this presentation
will not discuss ventilator
settings in detail.

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Ann Intensive Care. 2019;9(1):69.
Neuromuscular Blockade
 Improves lung compliance for patients on a vent
 Recommended to start within 48 hours for patients with PaO2/FIO2 <150 to
reduce mortality by some but controversial

 ACURASYS (N Engl J Med. 2010;363(12):1107-1116.)

 339 ARDS patients within 48 hours of progression; cisatracurium vs placebo
 No difference in 90-day mortality (31.6% vs 40.7%, p=0.08)
 HR 0.68 (95% CI 0.48-0.98) after adjustment
 Improved survival for pts with PaO2/FiO2 <120. More days alive and free of
vent at day 90 in NMB group (HR 1.41, p=0.01)
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Neuromuscular Blockade - Continued
 ROSE (N Engl J Med. 2019;380(21):1997-2008.)
 N=1006 patients with moderate to severe ARDS
 Randomized to 48-hour continuous infusion of cisatracurium with concomitant
deep sedation (intervention group) or to a usual-care approach without routine
neuromuscular blockade and with lighter sedation targets (control group)
 Trial ended early due to futility
 At 90 days, no difference in morality before discharge: 42.5% vs 42.8% control
 Increase rate of cardiovascular events

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 Neuromuscular Blockade - Conclusions

Recommend to
reserve paralytics for
Controversial for use
Inconsistent Evidence patients with ventilator
in all patients with
of Benefit dyssynchrony and
ARDS
moderate-to-severe
ARDS.

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MJ Open Respir Res. 2019;6(1):e000420.
Corticosteroids

Harm vs benefit consideration

Variable effects on mortality shown in

studies

Methylprednisolone most studied

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Corticosteroids –DEXA-ARDS
 DEXA-ARDS Protocol: Lancet Respir Med. 2020;8(3):267-276.
 N=277 patients at 17 ICUs in Spain with moderate-to-severe ARDS
 Dexamethasone 20 mg daily x5 days then 10 mg daily x5 days vs placebo
 Mean number of ventilator-free days was higher for the dexamethasone group
(mean difference 4.8 days [95% CI 2.57-7.03], p<0.001).
 Decreases in overall morality at 60 days were also seen with no significant
differences in the proportion of adverse events
 Limitations: unblinded; ended early d/t low enrollment
(limits safety data);
exclusion of patients who were DNR, CHF, severe COPD, or who provider
thought would benefit from steroids

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Corticosteroids - Conclusions

Minimize risks:
Consider in Use in viral glucose control,
patients with infections including consider
moderate-severe Covid-19 may be dexamethasone
ARDS beneficial over
mineralocorticoids

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 ECMO

 Consider in severe ARDS (ratio <80) or when

mechanical ventilation dangerous despite
optimization of other strategies
 EOLIA study (Engl J Med. 2018;378(21):1965-
1975.) did not have statistical significance for
60-day morality, but post-hoc analyses showed
high posterior probability of mortality reduction
 Most benefit might be for young, critically ill
patients
 ECMO is difficult to implement

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 Ineffective Treatments

Antioxidants
(vitamin C, Statins Surfactant
zinc, NAC)

Inhaled beta-
Ketoconazole And more!
agonists

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Minerva Anestesiol. 2015;81(5):567-588.

Long-Term Rehabilitation
 Patients may require long-term interventions

PEG /
Tracheostomy Nutritional PT/OT
Support

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Pharmacists’ Role in ARDS Management

Fluid Sedation and

Antibiotic
management- pain
management
Conservative! management

Renal and
hepatic Stress ulcer
DVT prophylaxis
adjustment of prophylaxis
medications
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ARDS due to Covid-19

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 ARDS due to Covid-19

Older Age and obesity are risk factors for

progression to ARDS.

Studies range 15-68% of hospitalized patients

developing ARDS (61-100% of ICU patients)

NIH Guidelines recommend use of NMBAs in

moderate-severe ARDS

Crit Care. 2020; 24: 516. 27

https://www.covid19treatmentguidelines.nih.gov/. Accessed Jan 26, 2021.
 Covid-19 ARDS - Dexamethasone
 RECOVERY (N Engl J Med.
2020;NEJMoa2021436.)
 Dexamethasone 6 mg daily for 10
days vs placebo
 For the subgroup of patients on
invasive mechanical ventilation at
baseline dexamethasone significantly
decreased mortality.

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COVID-19 ARDS - Remdesivir
 ACTT1 (N Engl J Med. 2020;383(19):1813-
1826.)
 Remdesivir vs placebo
 For the subgroup of patients
requiring mechanical ventilation or
ECMO at baseline, there was no
difference in recovery (discharge or
hospitalization only for infection
control).
 There was no difference in the
number of days requiring mechanical
ventilation or ECMO: 17 vs 20 (95%
CI -9.3 to 3.3)
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Conclusions

Acute respiratory distress syndrome is an inflammatory form of

lung injury with high mortality.
Supportive care with oxygenation and ventilation is key.
There are no drugs that consistently improve outcomes in clinical
trials though there is potential for benefit with steroids and
neuromuscular blockade in select patients.

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Acute Respiratory Distress
Syndrome (ARDS)
Maggie Kline, PharmD
PGY1 Pharmacy Resident