1. ARDS
Ruchi Kapoor
April 2015

2. A 34 year old paraplegic man with history of neurogenic bladder is admitted to the ICU for septic shock due to UTI. He is given IVF, Zosyn and intubated for decreased level of consciousness. CXR is normal with the ETT in the appropriate position.
2 days later he is evaluated for persistent hypoxemia on mechanical ventilation.
Vital Signs are: T 37.1 °C (98.8 °F), BP 90/50 mm Hg, HR 96/min, RR 26/min.
Oxygen saturation on an FIO2 of 0.8 is 89%.
Pulmonary examination reveals bilateral inspiratory crackles.
Cardiac examination reveals distant, regular heart sounds.

3. Lab results:
Hgb 13.2 g/dL
WBC 10,000/uL.
ABG on FiO2 80%: pH 7.48, pCO2 30 mm Hg, pO2 60 mmHg
Urine and blood cultures grow E. Coli that is sensitive to Zosyn.
Follow-up CXR shows diffuse bilateral infiltrates without cardiomegaly. CVP is 8 mm Hg.
Which of the following is the most likely cause of this patient's hypoxemia?
Acute respiratory distress syndrome
E. coli pneumonia
Heart failure
Idiopathic acute eosinophilic pneumonia

4. ABG on FiO2 80%: pH 7.48, pCO2 30 mm Hg, pO2 60 mmHg
Lab results:
Hgb 13.2 g/dL
WBC 10,000/uL.
ABG on FiO2 80%: pH 7.48, pCO2 30 mm Hg, pO2 60 mmHg
Urine and blood cultures grow E. Coli that is sensitive to Zosyn.
Follow-up CXR shows diffuse bilateral infiltrates without cardiomegaly. CVP is 8 mm Hg.
Which of the following is the most likely cause of this patient's hypoxemia?
Acute respiratory distress syndrome
E. coli pneumonia
Heart failure
Idiopathic acute eosinophilic pneumonia
Sepsis is one of the most common causes of ARDS, and onset within 48 to 72 hours after risk factor exposure is typical.
** FOR REFERENCE, DOES NOT HAVE TO BE PRESENTED **
Escherichia coli pneumonia is unlikely because hematogenous spread of infection to the lungs is unusual even in bacteremic patients. Sepsis-induced ARDS is much more likely.
Heart failure should be clinically excluded as the cause of acute bilateral alveolar infiltrates in patients being evaluated for ARDS. This patient's young age, normal central venous pressure, and absence of cardiomegaly on chest radiograph all make heart failure unlikely.
Idiopathic acute eosinophilic pneumonia is characterized by infiltration of the lung parenchyma by eosinophils. Patients present with fever, nonproductive cough, dyspnea, and bilateral infiltrates. Peripheral eosinophilia may not be present early in the course of illness, but prominent eosinophilia is present in bronchoalveolar lavage fluid. Idiopathic acute eosinophilic pneumonia, however, is rare and would be unlikely in a patient presenting with gram-negative infection and sepsis.

5. Objectives What is ARDS? – The Definition
Why does it happen? – The Pathophysiology
How to manage it? – The Basic Ventilation Strategy

6. What is ARDS? ARDS is lung injury that leads to: Impaired gas exchange
Decreased lung compliance
Increased pulmonary arterial pressure
Impaired gas exchange – due to V-Q mismatch
Decreased lung compliance – due to stiffness of poorly/non-aerated lung. Even small tidal volumes can cause dramatic rise in airway pressures. ARDS hallmark.
Pulmonary HTN – due to vasoconstriction, airway collapse, parenchymal destruction, positive airway pressure

7. Definition of ARDS Acute onset (within 1 week of clinical insult)
Bilateral pulmonary edema
PaO2/FiO2 <200 (or <300 if PEEP >5 cmH2O)
Exclude cardiogenic pulmonary edema

8. Risk Factors (i.e. “clinical insult”)
Sepsis
TRALI
Aspiration
Burns
Pneumonia
Drugs and alcohol
Pancreatitis
Lung transplant
Trauma
Hematopoietic stem cell transplant
Massive transfusion

9. Pathophysiology of ARDS
Starts with capillary endothelium. Ends with alveolar epithelium.
Capillary endothelium is activated.
Endothelium releases pro-inflammatory cytokines (e.g. TNF, IL-8) that recruit neutrophils to the lungs.
Neutrophils are activated and release toxic mediators (e.g. reactive oxygen species, proteases)
Causes further damage of capillary endothelium, and now of alveolar epithelium, leading to pulmonary edema.
The activation process of the endothelium is deregulated in ARDS.

10. Pulmonary Edema NORMAL ALVEOLI ALVEOLAR EDEMA
Alveolar lumen EMPTY of fluid
Pulmonary capillary
ALVEOLAR EDEMA
Alveolar lumen FULL of fluid
Interstitial fluid
Pulmonary capillary
Lymphatic movement
Breakdown of barriers
Protein
Normal: An osmotic gradient favoring fluid reabsorption from the interstitium is maintained by retention of serum proteins within the intravascular space. Fluid which does leak into the interstitium is transported to lymphatics from which it is returned to the circulation. Finally, tight junctions between alveolar epithelial cells prevent leakage of fluid into the alveolar space.
Alveolar edema:
Breakdown of the capillary endothelial barrier allows leakage of serum proteins into the interstitial space, undoing the osmotic gradient which normally promotes fluid reabsorption. Eventually, the quantity of fluid pouring from the capillaries overwhelms the capacity of the interstitium and the lymphatics, resulting in interstitial edema. Finally, breakdown of the alveolar epithelial barrier allows leakage of edema fluid into the alveolar space.

11. A 50-year-old previously health man is evaluated in the ICU for ARDS due to severe community-acquired pneumonia. He is intubated and placed on mechanical ventilation.
Vital Signs: 38.3 °C (100.9 °F), 120/60 mm Hg, 110 beats/min.
Oxygen saturation by pulse oximetry is 96%.
Physical exam is unremarkable except for bilateral inspiratory crackles.

12. Ideal Body weight is 60 kg.
Initial ventilator settings are volume control with
Rate 18 / TV 420 / PEEP 10 / FiO2 0.8
Peak pressure is 34 cm H2O. Plateau pressure is 32 cm H2O.
Which of the following is the most appropriate next step in management?
Decrease respiration rate
Decrease tidal volume
Increase FIO2
Increase PEEP

13. Initial ventilator settings are volume control with
Ideal Body weight is 60 kg.
Initial ventilator settings are volume control with
Rate 18 / TV 420 / PEEP 10 / FiO2 0.8
Peak pressure is 34 cm H2O. Plateau pressure is 32 cm H2O.
Which of the following is the most appropriate next step in management?
Decrease respiration rate
Decrease tidal volume
Increase FIO2
Increase PEEP
In patients with acute respiratory distress syndrome, a lung-protective strategy of low tidal volume (6 mL/kg predicted weight) and plateau pressure less than 30 cm H2O is associated with reduced mortality.
Decreasing tidal volume decreases plateau pressure, which in turn prevents overstretching of the lung.

14. Lung protective ventilation
Avoid further damage to an already edematous and injured lung by preventing overdistention of alveoli
Use Low Tidal Volume Ventilation (LTVV)
Based on predicted/ideal body weight, not actual body weight
Allow for permissive hypercapnia and respiratory acidosis.

15. Step-by-Step approach to Low Tidal Volume Ventilation
Set mode to volume assist-control
Set initial Tidal Volume (TV) to 8 mL/kg
Reduce TV to 7 then 6 mL/kg over 1-3 hrs
Keep plateau pressure (Pplat) 25 – 30 cm H20
Adjust FiO2 and PEEP to keep PaO2 55 – 80
FiO2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
PEEP 5
5 - 8
8 - 10 10 14
18 -24

16. A 63-year-old man with ARDS due to aspiration pneumonia is evaluated in the ICU. He has just been intubated and placed on mechanical ventilation
Vital signs: 37.0 °C (98.6 °F), 150/90 mm Hg, 108 beats/min.
Height: 150 cm (59 in)
Weight: 70.0 kg (154.3 lb).
Ideal body weight: 52.0 kg (114.6 lb).
Physical exam is only notable for crackles in the lower left lung field. Patient is sedated.

17. Mechanical ventilation is on the assist/control mode at a rate of 18/min. Positive end-expiratory pressure is 8 cm H2O, and FIO2 is 1.0.
Which of the following is the most appropriate tidal volume?
300 mL
450 mL
700 mL
840 mL

18. Which of the following is the most appropriate tidal volume? 300 mL
Mechanical ventilation is on the assist/control mode at a rate of 18/min. Positive end-expiratory pressure is 8 cm H2O, and FIO2 is 1.0.
Which of the following is the most appropriate tidal volume?
300 mL
450 mL
700 mL
840 mL
Survival is improved when patients with ARDS are ventilated with a tidal volume of 6 mL/kg of ideal body weight (IBW). IBW rather than actual body weight should be used to calculate tidal volume. In patients who are overweight or edematous, using actual body weight will typically result in inappropriately large tidal volumes. Large tidal volumes can lead to atelectrauma (lung injury that is presumed to arise from repetitive opening and closing of alveoli) and barotrauma. This can disrupt the alveolar capillary membrane, often referred to as ventilator-associated lung injury. 

19. Summary
ARDS is acute lung injury with bilateral pulmonary edema and hypoxia that is NOT cardiogenic in origin
ARDS occurs when capillary endothelium and alveolar epithelial barriers break down.
The cornerstone of management in ARDS is low- tidal volume ventilation to prevent overdistention of alveoli.

20. References
The ARDS Definition Task Force*. Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA. 2012;307(23): doi: /jama
Ferguson et al. The Berlin Definition of ARDS: An Expanded Rationale, Justification, and Supplementary Material. Intensive Care Med ;38(10): doi: /s
Piantadosi CA, Schwartz DA. The Acute Respiratory Distress Syndrome. Ann Intern Med. 2004;141: doi: /
The Acute Respiratory Distress Syndrome Network. 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 ;342(18): DOI: /NEJM
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