ACNP Boot Camp 2013
Stephanie Davidson, ACNP-BC

• Review the causes and differentials for ARDS
• Briefly discuss the pathophysiology
• Discuss the clinical manifestations of ARDS
• Understand evidence based treatment options

• 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

Trauma
13%
11%
Other
Aspiration
15%
Severe
Sepsis
26%
Pneumonia
35%
Other: drowning, pancreatitis, reperfusion, salicylate and narcotic OD, fat/amniotic embolism, smoke/chemical inhalation .
ARDS network N Engl J Med 2000; 342:1301

• 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 proinflammatory 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

• Consequences of lung injury include:
– Impaired gas exchange
– Decreased compliance
– Increased pulmonary arterial pressure

• 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

• Hallmark of ARDS
• Consequence of the stiffness of poorly or nonaerated lung
• Fluid filled lung becomes stiff/boggy
• Requires increased pressure to deliver Vt

• 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

• 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

• 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

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

• 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

• Higher levels of PEEP/FiO2 does not improve outcomes
– may negatively impact outcomes:
• Causing increased airway pressure
• Increase dead space
• Decreased venous return
• Barotrauma

• Positive End Expiratory Pressure
• Every ARDS patient needs it
• Goal is to maximize alveolar recruitment and prevent cycles of recruitment/derecruitment

• As FiO2 increases, PEEP should also increase
ARDSnet. NEJM 2004; 351, 327

• 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

• 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
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

• 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

• 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
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

• Daily CPAP breathing trial
– FiO2 <.40 and PEEP <8
– Patient has acceptable spontaneous breathing efforts
– No vasopressor requirements
• Pressure support weaning
– PEEP 5, PS at 5cm H 2 O if RR <25
– If not tolerated, ↑RR, ↓Vt – return to A/C
• Unassisted breathing
– T-piece, trach collar
– Assess for 30minutes-2 hours

• 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

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 card

• Mechanical Trouble (tubing, ventilator, ptx, plugging)
• Neuromuscular blockade
• Recruitment maneuvers - positioning
• Increase PEEP
• Inhaled epoprostenol sodium (Flolan)
• High frequency ventilation

• 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

• 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

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.
Guerin C et al: Prone positioning in severe acute respiratory distress syndrome. New
Engl J Med. 2013; 368: 2159-2168.

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.
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.
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.
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.