TREATMENT

OF ARDS
SV, MSIV
SEPTEMBER 5, 2012

WHAT IS ACUTE RESPIRATORY

DISTRESS SYNDROME (ARDS)?
A type of acute diffuse, inflammatory lung injury, leading to
increased pulmonary vascular permeability, increased lung
weight, and loss of aerated lung tissue. The clinical
hallmarks are hypoxemia and bilateral radiographic
opacities, associated with increased venous admixture,
increased physiological dead space, and decreased lung
compliance. The morphological hallmark of the acute phase
is diffuse alveolar damage (i.e., edema, inflammation, hyaline
membrane, or hemorrhage). 1

DEFINITIONS
AECC Definition (1994):

Acute onset
PaO2/FiO2 < 200 mm Hg (<300 mm Hg in ALI)
Bilateral pulmonary infiltrates on radiography
Exclude cardiogenic pulmonary edema: PCWP <18 mm Hg or clinically

Berlin Definition (2012)1:

Within 1 week of known insult or new/worsening respiratory symptoms

Bilateral opacities not fully explained by effusions, lobar/lung collapse, or
nodules on Chest CT or CXR
Respiratory failure not fully explained by cardiac failure or fluid overload.
Objective assessment required to exclude hydrostatic edema if no risk
factors present (e.g. echo)
Oxygenation:

Mild - 200 mm Hg < PaO2/FiO2 < 300 mm Hg w/PEEP or CPAP > 5 cm H20
Moderate - 100 mm Hg < PaO2/FiO2 < 200 mm Hg w/PEEP > 5 cm H20
Severe - 100 mm Hg < PaO2/FiO2 w/PEEP > 5 cm H20

ETIOLOGY
Acute alveolar-capillary injury is triggered by wide range of
primary disease processes3,4:
Infection: Sepsis (MCC, 18-38%), pneumonia
Severe Trauma, Burns, Multiple/Long Bone FX
Aspiration, Drug Overdose
Massive/Multiple Transfusion
Acute pancreatitis

TREATMENT STRATEGIES
Mechanical Ventilation
Supportive care
Treat underlying cause will not resolve otherwise

E.g. Appropriate ABX for sepsis

Debridement, drainage, resection when source

Conservative fluid management

Nutrition
DVT, GI Prophylaxis, Turning, Early removal of lines

MECHANICAL VENTILATION
Low tidal volume ventilation and PEEP
Initial hypoxemia may require high FiO2
Appropriate sedation and pain control
Daily interruption of sedation, SBT to facilitate wean
Patients who survive initial course usually exhibit better
oxygenation and decreased infiltrates over next several
days
Some patients have persistent infiltrates and remain ventdependent
Tracheostomy may be required for prolonged mechanical
ventilation
Can take weeks to months to resolve

MECHANICAL VENTILATION
ARMA trial showed lower tidal volume ventilation (<6ml/kg
PBW, plateau pressures <30 cm H2O) had significantly
lower in-hospital mortality and significantly higher # of
days w/o mechanical ventilation2,5.
ALVEOLI study7 and meta-analysis of multiple RCTs6 failed
to show mortality benefit in higher vs. lower PEEP values
in patients with ALI and ARDS. However in patients with
ARDS, higher PEEP values may have a relative mortality
reduction, where as patients with ALI have no benefit or
may be harmed6.

MECHANICAL VENTILATION*
Start with initial tidal volume 8 ml/kg*PBW

PBW = 2.3 *(height in inches - 60) + 45.5 (women) or + 50 (men)

RR < 35 to deliver expected minute ventilation (7-9 L/min)

Set PEEP to least 5 cm H2O and titrate FiO2 to maintain
SaO2 88-95% (PaO2 55-80 mm Hg)

Reduce tidal volumes by 1 ml/kg to 6 ml/kg w/in 4 hours

Adjust tidal volume and RR to meet pH (7.3-7.45) and
plateau pressure goals (< 30 cm H2O)
Spontaneous breath trial after criteria have been met

*http://www.ardsnet.org/system/files/Ventilator Protocol Card.pdf

FLUID MANAGEMENT
ARDS Net FACTT trial:
Early aggressive fluid resuscitation in sepsis, then either
liberal or conservative fluid management

Initiated ~42hrs after ICU admission

No mortality benefit to conservative (net even, CVP <4 mm Hg)

versus liberal (~1L/day, CVP 10-14 mm Hg) fluid management10.

Conservative strategy improved oxygenation, reduced time on

vent without increase in shock and non-pulmonary organ failure
(e.g. kidneys).

No benefit to PAC vs. Central Venous Catheter for fluid

management. Complications from PAC11.

NUTRITION
Institution of nutritional support 48-72 hours after
mechanical ventilation recommended
Tube feed preferred to TPN unless contraindicated (acute
abdomen, GI bleed, etc.)
Initial trophic (~400 kcal/day) enteral feeding for up to 6
days did not improve ventilator-free days, 60-day
mortality, or infectious complications but was associated
with less gastrointestinal intolerance8

RESCUE THERAPIES
No proven mortality reduction, but decrease hypoxemia2:
Recruitment maneuvers
ECMO and ECCO2R
Prone position

Corticosteroids are used clinically. Low doses in persistent

ARDS, increase ventilator free days, but concern is for
hyperglycemia and neuromuscular side effects12.
Vasodilators: gas exchange in well-ventilated areas

Inhaled Nitric Oxide (iNO) or inhaled prostacylcine

Vasoconstrictors: intrapulmonary shunting

Phenylephrine, almitrine, -Blocker

What doesnt Work?

Anti-inflammatory medications (ibuprofen, ketoconazole,
many others)2,12
Surfactant2
-2 agonist therapy, inhaled or IV2,12
Older studies suggested eicosapentanoic acid and linoleic acid and -3 fatty acids increased oxygenation
and decreased ICU stay and 28-day mortality in ARDS2,
but EDEN-Omega study showed no benefit2,9

COMPLICATIONS FROM
TREATMENT
Ventilator associated pneumonia
Barotrauma, PTX, post extubation laryngeal edema,
subglotic stenosis
Line sepsis
Drug resistant infections (MRSA, VRE)
Persistent impairment after recovery Exercise, QoL even
after 5 years13

FURTHER RESEARCH
Pressure controlled ventilation and high frequency
oscillatory ventilation
Neuromuscular blocking agents (cisatracurium)
Statin therapy
Anti TNF- antibody, IL-1 Receptor antagonist

REFERENCES
1.

Acute respiratory distress syndrome: the Berlin Definition. ARDS Definition Task Force et al. JAMA. 2012 Jun
20;307(23):2526-33.

2.

Acute Respiratory Distress Syndrome: Pathophysiology and Therapeutic Options. Pierrakos C., et al. J Clin Med Res. 2012
February; 4(1): 716.

3.

Incidence and Outcomes of Acute Lung Injury. Gordon D., et al. N Engl J Med. 2005; 353:1685-1693

4.

Clinical Characteristics and Outcomes of Sepsis-Related vs Non-Sepsis-Related ARDS. Sheu C., et al. Chest. 2010
September; 138(3): 559567

5.

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. N Engl J Med. 2000; 342:1301-1308

6.

Higher vs Lower Positive End-Expiratory Pressure in Patients With Acute Lung Injury and Acute Respiratory Distress
Syndrome: Systematic Review and Meta-analysis. Briel M., et al. JAMA. 2010;303(9):865-873.

7.

Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. Brower
RG, et al. N Engl J Med. 2004 Jul 22;351(4):327-36

8.

Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury. JAMA. 2012;307(8):795-803.

9.

Enteral Omega-3 Fatty Acid, -Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury. Rice T., et al. JAMA.
2011;306(14):1574-1581.

10.

Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15; 354(24):2564-75.

11.

Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med. 2006 May 25;
354(21):2213-24.

12.

ARDS Network (NHLBI) Studies Successes and Challenges in ARDS Clinical Research. Crit Care Clin. 2011 July; 27(3):
459468.

13.

Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011; 364(14):1293-304

14.

http://emedicine.medscape.com/article/165139-overview

15.

http://www.uptodate.com