Acute Respiratory Distress

Syndrome
ACNP Boot Camp 2014
Stephanie Davidson, ACNP-BC
 Objectives
• Review the causes and differentials for ARDS
• Briefly discuss the pathophysiology
• Discuss the clinical manifestations of ARDS
• Understand evidence based treatment options
 Statistics
• Epidemiology
– Annual incidence: 60/100,000
– 20% ICU patients meet criteria for ARDS
• Morbidity / Mortality
– 26-44%, most (80%) deaths attributed to non-pulmonary
organ failure or sepsis
• Risk Factors
– Advanced age, pre-existing organ dysfunction or chronic medical
illness
– Patient with ARDS from direct lung injury has higher incidence of
death than those from non-pulmonary injury

Levy BD, & Choi AM, Harrison’s Principles of Internal Medicine, 2012
Bernard et al. AJRCCM 1994; 149:818
Rice et al. Chest 2007: 132: 410
 June 20, 2012, Vol 307, No. 23

-European Society of Intensive Care Medicine with endorsement from

American Thoracic Society and Society of Critical Care Medicine
-Devised three mutually exclusive severity categories: Mild, Moderate
and Severe
-Took into account: timing, chest imaging, origin of edema, oxygenation

et al. JAMA 2012; 307:2530

et al. JAMA 2012; 307:2530
Pneumonia
35%

ARDS network N Engl J Med 2000; 342:1301

 Differentials
• Left ventricular failure/volume overload
• Mitral stenosis
• Pulmonary veno-occlusive disease
• Lymphangitic spread of malignancy
• Interstitial and/or airway disease
– Hypersensitivity pneumonia
– Acute eosinophilic pneumonia
– Acute interstitial pneumonitis
 Pathophysiology
1. Direct or indirect injury to
the alveolus causes alveolar
macrophages to release pro-
inflammatory cytokines

Ware et al. NEJM 2000; 342:1334

 Pathophysiology
2. Cytokines attract
neutrophils into the alveolus
and interstitum, where they
damage the alveolar-capillary
membrane (ACM).

Ware et al. NEJM 2000; 342:1334

 Pathophysiology
3. ACM integrity is lost,
interstitial and alveolus fills with
proteinaceous fluid, surfactant
can no longer support alveolus

Ware et al. NEJM 2000; 342:1334

 Pathophysiology
• Consequences of lung injury include:
– Impaired gas exchange
– Decreased compliance
– Increased pulmonary arterial pressure
 Impaired Gas Exchange
• V/Q mismatch
– Related to filling of alveoli
– Shunting causes hypoxemia
• Increased dead space
– Related to capillary dead space and V/Q mismatch
– Impairs carbon dioxide elimination
– Results in high minute ventilation
 Decreased Compliance
• Hallmark of ARDS
• Consequence of the stiffness of poorly or
nonaerated lung
• Fluid filled lung becomes stiff/boggy
• Requires increased pressure to deliver Vt
Increased Pulmonary Arterial Pressure
• Occurs in up to 25% of ARDS patients
• Results from hypoxic vasoconstriction
• Positive airway pressure causing vascular
compression
• Can result in right ventricular failure
• Not a practice we routinely measure
Evidence based management of ARDS
• Treat the underlying cause
• Low tidal volume ventilation
• Use PEEP
• Monitor Airway pressures
• Conservative fluid management
• Reduce potential complications
 Hypothesis:
In patients with ALI, ventilation with smaller tidal volumes (6 mL/kg)
will result in better clinical outcomes than traditional tidal volumes (12
mL/kg) ventilation.

ARDS Network N Engl J Med 2000; 342:1301

 Low Tidal Volume Ventilation
• When compared to larger tidal volumes, Vt of 6ml/kg of ideal
body weight:
• Decreased mortality
• Increased number of ventilator free days
• Decreased extrapulmonary organ failure
• Mortality is decreased in the low tidal volume group despite
these patients having:
• Worse oxygenation
• Increased pCO2 (permissive hypercapnia)
• Lower pH

ARDSnet. NEJM 2000; 342: 1301

 Low Tidal Volume Ventilation
ARDS affects the lung in a
heterogeneous fashion
• Normal alveoli
• Injured alveoli can
potentially participate in gas
exchange, susceptible to
damage from opening and
closing
• Damaged alveoli filled with
fluid, do not participate in
gas exchange
 Low Tidal Volume Ventilation
• Protective measure to avoid over distention of
normal alveoli
• Uses low (normal) tidal volumes
• Minimizes airway pressures
• Uses Positive end-expiratory pressure (PEEP)
 Hypothesis:
In patients with ALI ventilated with 6 mL/kg, higher levels of
PEEP will result in better clinical outcomes than lower levels of
PEEP.

N Engl J Med 2004; 351:327

 PEEP
• Higher levels of PEEP/FiO2 does not improve
outcomes
– may negatively impact outcomes:
• Causing increased airway pressure
• Increase dead space
• Decreased venous return
• Barotrauma
 PEEP
• Positive End Expiratory Pressure
• Every ARDS patient needs it
• Goal is to maximize alveolar recruitment and
prevent cycles of recruitment/derecruitment
-983 patients, randomized into control group with ALI protocol, low Vt and
PEEP vs. Open lung group with low Vt, higher PEEP and recruitment
maneuvers
-No statistically significant difference in mortality outcomes

Meade, M et al, JAMA. 2008; 299(6):637-645

-Multicenter randomized trial, 767 patients. Set a PEEP aimed to increase
alveolar recruitment while limiting hyperinflation
-Randomly assigned two groups: moderate PEEP (5-9cm H2O) vs. level of
PEEP to reach a plateau pressure of 28-30cm H2O
-Found that it didn’t significantly reduce mortality; however, it did improve lung
function and decreased days on vent and organ failure duration

Mercatt, M, et al. JAMA. 2008; 299(6):646-655.

 PEEP
• As FiO2 increases, PEEP should also increase

ARDSnet. NEJM 2004; 351, 327

Auto Peep
 Airway Pressures in ARDS
• Plateau pressure is most predictive of lung injury
• Goal plateau pressure < 30, the lower the better
• Decreases alveolar over-distention and reduces risk of
lung strain
• Adjust tidal volume to ensure plateau pressure at goal
• It may be permissible to have plateau pressure > 30 in
some cases
• Obesity
• Pregnancy
• Ascites
Terragni et al. Am J Resp Crit Care Med. 2007;
175(2):160
 Permissible Plateau Pressures
• Assess cause of high Plateau Pressures
• Always represents some pathology:
– Stiff, non-compliant lung: ARDS, heart failure
– Pneumothorax
– Auto-peeping
– Mucus Plug
– Right main stem intubation
– Compartment syndrome
– Chest wall fat / Obesity
 Airway Pressures
Peak Inspiratory Pressure
Airway
Pressures
Plateau Pressure

PEEP

Time
Fluid and Catheter Treatment Trial
--No need for routine PAC use is ALI patients
--Support use of conservative strategy fluid management in patients
with ALI

N Engl J Med 2006; 354: 2213

 Results
• Using the data from a PAC compared to that from a CVC in
an explicit protocol:
– Did not alter survival.
– Did not improve organ function.
– Did not change outcomes for patients entering in shock
compared to those without shock.
• PAC use resulted in more non-fatal complications, mostly
arrhythmias.

N Engl J Med 2006; 354: 2213

~Hypothesis: Diuresis or fluid restriction may improve lung function but
could jeopardize extrapulmonary organ perfusion

~Conclusion: Conservative fluid management improved lung function and

shortened mechanical ventilation times and ICU days without increasing
nonpulmonary organ failures

N Engl J Med. 2006;354:2564

Fluid Management
• Increased lung water is the
underlying cause of many of
the clinical abnormalities in
ARDS (decreased compliance,
poor gas exchange,
atelectasis)
• After resolution of shock, effort
should be made to attempt
diuresis
• CVP used as guide, goal <4
• Shortens time on vent and ICU
length of stay (13 days vs 11
days)

ARDSnet. NEJM 2006; 354: 2564

Hypothesis: Early application of prone positioning would
improve survival in patients with severe ARDS.

Conclusion: Early application of prolonged prone positioning

significantly decreased 28 day and 90 mortality in patients with
severe ARDS.

Guerin et al. NEJM. 2013; 368:2159

 Weaning
• Daily CPAP breathing trial
– FiO2 <.40 and PEEP <8
– Patient has acceptable spontaneous breathing efforts
– No vasopressor requirements, use judgement
• Pressure support weaning
– PEEP 5, PS at 5cm H2O if RR <25
– If not tolerated, ↑RR, ↓Vt – return to A/C
• Unassisted breathing
– T-piece, trach collar
– Assess for 30minutes-2 hours
 Weaning
• Tolerating Breathing Trial?
– SpO2 ≥90
– Spontaneous Vt ≥4ml/kg PBW
– RR ≤35
– pH ≥7.3
– Pass Spontaneous Awakening Trial (SAT)
– No Respiratory Distress ( 2 or more)
• HR > 120% baseline
• Accessory muscle use
• Abdominal Paradox
• Diaphoresis
• Marked Dyspnea
– If tolerated, consider extubation
 Putting it all together
1) Calculate patient’s predicted body weight:
• Men (kg) = 50 + 2.3(height in inches – 60)
• Females (kg) = 45.5 + 2.3(height in inches – 60)
2) Set Vt = predicted body weight x 6cc
3) Set initial rate to approximate baseline minute
ventilation (RR x Vt)
4) Set FiO2 and PEEP to obtain SaO2 goal of >=88%
5) Diurese after resolution of shock
6) Refer to ARDSnet guidelines
Troubleshooting Common Problems
 Refractory Hypoxia
• Mechanical Trouble (tubing, ventilator, ptx, plugging)
• Neuromuscular blockade
• Recruitment maneuvers – positioning, “good lung down”
optimizes V/Q mismatch
• Increase PEEP
• Inhaled epoprostenol sodium (Flolan)
– When inhaled, the vasodilator reaches the normal lung, is
concentrated in normal lung segments and recruits blood flow to
functional alveoli where it is oxygenated. This decreases shunting and
hypoxemia
• High frequency ventilation
-Randomized control trial, stopped with 548 of 1200 patients
-Found early initiation of HFOV does not reduce and may increase
hospital mortality

Ferguson, N, et al, NEJM 2013; 368: 795-805.

-Multicenter randomized trial with 795 patients enrolled
-found there is no significant effect of 30 day survival between patients who
received HFOV and conventional mechanical ventilation

Young, D, et al,NEJM. 2013; 368:806-813

-Neuromuscular blocking agents may increase oxygenation and decrease
ventilator associated lung injury in severe ARDS patients
-Multicenter double blind trial with 340 patients; received 48hrs of
cisatracurium (Nimbex) or placebo
-Found that early administration of NBA improved 90 day survival and
increased time off vent without increase in muscle weakness

Papazian, L, et al. NEJM 2010; 363: 1107-1116.

 Supportive Therapies
• Treat underlying infection
• DVT prophylaxis / stress ulcer prevention
• HOB 30°
• Hand washing
• Use full barriers with chlorhexadine
• Sedation / analgesia
• Feeding protocol
• Avoid contrast nephropathy
• Pressure ulcer prevention, turning Q2h
• Avoid steroid use
~No benefit of corticosteroids on survival

~When initiated 2 weeks after onset of ARDS, associated with significant

increase in mortality rate compared to placebo group

N Engl J Med. 2006; 354:1671

 Conclusion
• Recovery dependent on health prior to onset
• Within 6 months, will have reached max recovery
• At 1 year post-extubation, >1/3 have normal spirometry
• Significant burden of emotional and depressive symptoms
with increased depression and PTSD in ARDS survivors
• Survivor clinic catches symptoms early by screening patients
• New treatment modalities, lung protective ventilation

Levy BD, & Choi AM, Harrison’s Principles of Internal Medicine, 2012
Questions ?
 References
Acute Respiratory Distress Syndrome Network: Ventilation with Tidal Volumes as
compared with traditional tidal volumes for acute lung injury and the acute
respiratory distress syndrome. New Engl J Med. 2000; 342: 1302-1308.
ARDSNet: Higher versus lower Positive End-Expiratory Pressures in patients with the
acute respiratory distress syndrome. New Engl J Med. 2004; 351: 327-336.
ARDSNet: Efficacy and Safety of Corticosteroids for persistent acute respiratory
distress syndrome. New Engl J Med. 2006; 354: 1671-1684.
ARDSNet: Comparison of Two fluid management strategies in acute lung injury. New
Engl J Med. 2006; 354: 2564-75.
ARDSNet: Pumonary Artery versus Central Venous catheter to guide treatment of
acute lung injury. New Eng J Med. 2006; 354: 2213-2224.
Et al: Acute respiratory distress syndrome: The Berlin Definition. JAMA. 2012;
307(23): 2526-2533.
Ferguson N, et al: High frequency oscillation in early acute respiratory distress
syndrome. New Engl J Med. 2013; 368: 795-805.
Guerin C et al: Prone positioning in severe acute respiratory distress syndrome. New
Engl J Med. 2013; 368: 2159-2168.
 References
Levy B.D., Choi A.M. (2012). Chapter 268. Acute Respiratory Distress Syndrome. In A.S.
Fauci, D.L. Kasper, J.L. Jameson, D.L. Longo, S.L. Hauser (Eds), Harrison's Principles
of Internal Medicine, 18e. Retrieved August 17, 2013 from
http://www.accesspharmacy.com.proxy.library.vanderbilt.edu/content.aspx?aID=
9105737.
Meade M, et al: Ventilation Strategy Using low tidal volumes, recruitment maneuvers
and high post end expiratory pressure for acute lung injury and acute respiratory
distress syndrome. JAMA. 2008; 299(6):637-645.
Mercatt M, et al: Post end-expiratory pressure settings in adults with acute lung injury
and acute respiratory distress syndrome. JAMA. 2008; 299(6): 645-655.
Papazian L, et al: Neuromuscular blockers in early acute respiratory distress syndrome.
New Engl J Med. 2010; 363:1107-1116.
RiceTW et al: Comparison of the SpO2/FiO2 Ration and the PaO2/FiO2 Ratio in
patients with acute lung injury or acute respiratory distress syndrome. Chest.
2007; 132: 410-417.
 References
Terragan PP et al: Tidal hyperinflation during low tidal volume ventilation in Acute
respiratory distress syndrome. J Resp Crit Care Med. 2007; 175: 160-166
Ware LB, Matthay MA: The Acute Respiratory Distress Syndrome. New Engl J Med.
2000; 342: 1334-1349.
Young D, et al: High frequency oscillation for acute respiratory distress syndrome.
New Engl J Med. 2013; 368:806-813.