1. Respiratory Failure/ ARDS
Ian B. Hoffman, MD, FCCP
Pulmonary & Critical Care Medicine
September 4, 2013

2. A 32-year-old man is evaluated for persistent hypoxemia on mechanical ventilation in the intensive care unit. His medical history is significant for paraplegia and a chronic indwelling urinary catheter for neurogenic bladder. He presented to the emergency department 2 days ago with sepsis. At that time, he received piperacillin/tazobactam, normal saline, and vasopressors. He was endotracheally intubated for decreased level of consciousness. His initial chest radiograph was normal.
On physical examination on the second day of hospitalization, temperature is 37.1 °C (98.8 °F), blood pressure is 90/50 mm Hg, pulse rate is 96/min, and respiration rate is 26/min. His need for supplemental oxygen has steadily increased; his oxygen saturation on an FIO2 of 0.8 is 89%. Pulmonary examination reveals bilateral inspiratory crackles. Cardiac examination reveals distant, regular heart sounds.
Urine and blood cultures are positive for Escherichia coli. A follow-up chest radiograph shows diffuse bilateral infiltrates without cardiomegaly. Central venous pressure is 8 mm Hg.
Laboratory studies:
Hemoglobin
13.2 g/dL (132 g/L)
Leukocyte count
10,000/µL (10 × 109/L)
Arterial blood gas studies (on an FIO2 of 0.8): pH
7.48
PCO2
30 mm Hg (4.0 kPa)
PO2
60 mm Hg (8.0 kPa)

3. Which of the following is the most likely cause of this patient’s hypoxemia?
Acute respiratory distress syndrome
E. coli pneumonia
Heart failure
Eosinophilic pneumonia

4. Respiratory Failure
Any disruption of function of respiratory system – CNS, nerves, muscles, pleura, lungs
Any process resulting in low pO2 or high pCO2 – arbitrarily 50/50
Acute respiratory failure can be exacerbation of chronic disease or acute process in previously healthy lungs

5. History 1940’s – polio, barbiturate OD
1960’s – blood gas analysis readily available, aware of hypoxemia
1970’s – decreased hypoxic mortality, increased multiorgan failure (living longer)
1973 – relationship between resp muscle fatigue and resp failure

6. Types of Respiratory Failure
Type 1 (nonventilatory) – hypoxemia with or without hypercapnia – disease involves lung itself (i.e, ARDS)
Type 2 – failure of alveolar ventilation – decrease in minute ventilation or increase in dead space (i.e. COPD, drug OD)

7. Goals of Treatment
Correct hypoxemia or hypercapnia without causing additional complications
Noninvasive ventilation vs. intubation and mechanical ventilation
Goal of mechanical ventilation is NOT necessarily to normalize ABGs

8. Ventilation–perfusion (V/Q) relationships and associated blood gas abnormalities
Shunt

9. The influence of shunt fraction on the relationship between the inspired oxygen (FiO2) and the arterial PO2 (PaO2).

10. Ventilatory Failure VCO2 VA
Failure of respiratory pump to adequately eliminate CO2
pCO2 :
VCO2 determined by rate of total body metabolism
VCO2 VA

11. ALVEOLAR HYPOVENTILATION IN THE ICU

12. Respiratory Muscles Acute or acute-on-chronic overloading
COPD, hyperinflation, fatigue
Electrolyte imbalances
Sepsis
Shock
Malnutrition
Drugs
Atrophy related to prolonged mechanical ventilation
Hypothyroidism
Myopathies

13. What factors leading to respiratory muscle weakness can be reversed?
Reduce respiratory load
treat asthma, COPD, upper airway problems
treat pneumonia, pulm edema, reduce dynamic hyperinflation, drain large pleural effusions, evacuate PTX
Replace K, Mg, PO4, Ca
Treat sepsis
Nutritional support w/o overfeeding
Rest muscles hrs, then exercise
Stop aminoglycosides
Rule out hypothyroidism, oversedation, critical illness myopathy/neuropathy

14. To intubate or not Decision to mechanically ventilate is clinical
Some criteria:
Decreased level of consciousness (ER always tells us that GCS = 3 and pt tubed to protect airway!)
Vital capacity <15 ml/kg
Severe hypoxemia
Hypercarbia (acute or acute-on-chronic)
Vd/Vt >0.60
NIF < -25 cm H20

15. ARDS – Acute Respiratory Distress Syndrome

16. ARDS - Definition Severe end of the spectrum of acute lung injury
Diffuse alveolar damage
Acute and persistent lung inflammation with increased vascular permeability – inflammatory cytokines
Diffuse infiltrates
Hypoxemia
No clinical evidence of elevated left atrial pressure (PCWP <18 if measured)

17. ARDS – History/Definitions
1967 – Ashbaugh described 12 pts with acute respiratory distress, refractory cyanosis, decreased lung compliance, diffuse infiltrates; 7 of the 12 died
1988 – 4 point lung injury score (level of PEEP, pO2/FiO2, lung compliance, degree of infiltrates)
1994 – acute onset, bilateral infiltrates, no direct or clinical evidence of LV failure, pO2/FiO2)

18. 1994 American European Consensus
Acute Lung Injury
ARDS
Acute onset
Bilateral infiltrates c/w pulmonary edema
No clinical evidence of left-sided CHF (PCWP <18)
paO2/FiO2 ratio <300
Acute onset
Bilateral infiltrates c/w pulmonary edema
No clinical evidence of left-sided CHF (PCWP <18)
paO2/FiO2 ratio <200
100/0.40 = 250
100/0.60 = 167

19. New Definition of ARDS - 2012
Acute onset (within 7 days of some defined event)
Bilateral infiltrates (on CXR or CT)
No need to exclude heart failure (respiratory failure “not fully explained by CHF”)
Hypoxemia – mild, moderate, severe

20. Severity of ARDS (2012) ARDS Severity PaO2/FiO2 (on PEEP 5) Mortality
Mild
27%
Moderate
32%
Severe
<100
45%

21. ARDS - Incidence Annual incidence 75 per 100,000 (1977)
9% of American critical care beds occupied by pts with ARDS

22. ARDS - Diagnosis
Clinically and radiographically resembles cardiogenic pulmonary edema
PCWP can be misleading – should be normal or low, but can be high
20% of pts with ARDS may have LV dysfunction

24. ARDS - Causes Direct injury to the lung
Indirect injury to the lung in setting of systemic process
Multiple predisposing disorders substantially increase risk
Increased risk with alcohol abuse, chronic lung disease, acidemia

25. ARDS - Causes Direct Lung Injury Indirect Lung Injury Pneumonia
Gastric aspiration
Lung contusion
Fat emboli
Near drowning
Inhalation injury
Reperfusion injury
Indirect Lung Injury
Sepsis
Multiple trauma
Cardiopulm bypass
Drug overdose
Acute pancreatitis
Blood transfusion

26. ARDS - Physiologic Derangements
Inflammatory injury producing diffuse alveolar damage
Alveolar epithelium (eg, aspiration)
Vascular endothelium (eg, sepsis)
Proinflammatory cytokines (TNF, IL-1, IL-8)
Neutrophils recruited – release toxic mediators
Normal barriers to alveolar edema are lost, protein and fluid flow into air spaces, surfactant lost, alveoli collapse; inhomogeneous process
Impaired gas exchange
Decreased compliance
Pulmonary hypertension

27. ARDS – Features Severe initial hypoxemia
Increased work of breathing (decreased compliance) – generally a prolonged need for mechanical ventilation
Initial exudative stage
Proliferative stage
resolution of edema, proliferation of type II pneumocytes, squamous metaplasia, collagen deposition
Fibrotic stage

28. ARDS – Course Early Subsequent
Inciting event pulmonary dysfunction (worsening tachypnea, dyspnea, refractory hypoxemia)
Nonspecific labs
CXR – diffuse alveolar infiltrates
Subsequent
Eventual improvement in oxygenation
Continued ventilator dependence
Complications
Large dead space, high minute ventilation requirement
Organization and fibrosis in proliferative phase

30. ARDS - Complications Ventilator induced lung injury
Sedation and neuromuscular blockade
Nosocomial infection
Pulmonary emboli
Multiple organ dysfunction

31. ARDS - Prognosis
Improved survival in recent years – mortality was 50-60% for many years, now 35-40%
Improvements in supportive care, improved mechanical ventilatory management
Early deaths (3 days) usually from underlying cause of ARDS
Later deaths from nosocomial infections, sepsis, MOSF
Respiratory failure only responsible for ~16% of fatalities
Long-term survivors usually show mild abnormalities in pulmonary function (DLCO)

32. Question 2
A 63-year-old man with acute respiratory distress syndrome (ARDS) is evaluated in the intensive care unit. He has just been intubated and placed on mechanical ventilation for ARDS secondary to aspiration pneumonia. Before intubation, his oxygen saturation was 78% breathing 100% oxygen with a nonrebreather mask.
On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 150/90 mm Hg, and pulse rate is 108/min. His height is 150 cm (59 in) and his weight is 70.0 kg (154.3 lb). Ideal body weight is calculated to be 52.0 kg (114.6 lb). Central venous pressure is 8 cm H2O. Cardiac examination reveals normal heart sounds and no murmurs. Crackles are auscultated in the lower left lung field. The patient is sedated. Neurologic examination is nonfocal.
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.

33. Which of the following is the most appropriate tidal volume?
300 ml
450 ml
700 ml
840 ml

34. Ventilatory Goals in ARDS
Provide adequate oxygenation without causing damage related to:
Oxygen toxicity
Hemodynamic compromise
Barotrauma
Alveolar overdistension
Alveolar shear

35. Mechanical Ventilation in ARDS
Reliable oxygen supplementation
Decrease work of breathing
Increased due to high ventilatory requirements, increased dead space, and decreased compliance
Recruitment of atelectatic lung units
Decreased venous return can help decrease fluid movement into alveolar spaces

36. Ventilator Induced Lung Injury
Known for decades that high levels of positive pressure ventilation can rupture alveolar units
In 1950’s became known that high FiO2 can produce lung injury
More recently, effects of alveolar overdistension, shearing, cyclical opening and closing have become apparent

37. Ventilator Induced Lung Injury
Macrobarotrauma
Pneumothorax, interstitial emphysema, pneumomediastinum, SQ emphysema, pneumoperitoneum, air embolism
? resulting from high airway pressures, or just a marker of severe lung injury
Higher PEEP predicts barotrauma

38. Ventilator Induced Lung lnjury
Microbarotrauma
Alveolar overinflation exacerbating and perpetuating lung injury – edema, surfactant abnormalities, inflammation, hemorrhage
Less affected lung accommodates most of tidal volume – regional overinflation
Cyclical atelectasis (shear) – adds to injury
Low tidal volume strategy (initial tidal volume 6 ml/kg IBW, plateau pressure <30) – lower mortality

40. Ventilatory Strategies
Therapeutic target of mechanical ventilation in patients with ARDS has shifted from maintenance of "normal gas exchange” to the protection of the lung from ventilator-induced lung injury
Low tidal volume, plateau pressure <30 peak pressure = large airways plateau pressure = small airways/alveoli
PEEP – enough, not too much
Pressure controlled vs. volume cycled
Prolonging inspiratory time (increase mean airway pressure and improve oxygenation)
APRV
Recent data suggests high frequency oscillation is bad
Permissive hypercapnia
Secondary effect of low tidal volumes
Maintain adequate oxygenation with less risk of barotrauma
Sedation/paralysis often necessary

41. The only method of mechanical ventilation that has been shown in randomized controlled trials to improve survival in patients with ARDS is low tidal volume ventilation.

42. ARDS Network Trial
NEJM 2000; 342:
Initial tidal volume of 6 ml/kg IBW and plateau pressure < vs Initial tidal volume of 12 ml/kg IBW and plateau pressure <50
Reduction in mortality of 22% (31% vs 40%)

44. Ventilator management in patients with acute respiratory distress syndrome or acute lung injury
N Engl J Med 2000; 342:1301

45. Question 3
A 25-year-old woman is admitted to the intensive care unit (ICU) for a 6-hour history of respiratory distress. She has acute lymphoblastic leukemia and received cytotoxic chemotherapy 2 weeks before ICU admission. She has had fever and leukopenia for 7 days.
On physical examination, she is in marked respiratory distress. Temperature is 39.0 °C (102.2 °F), blood pressure is 110/70 mm Hg, pulse rate is 130/min, and respiration rate is 42/min. Weight is 50.0 kg (110.2 lb). Ideal body weight is calculated as 50.0 kg (110.2 lb).
Acute respiratory distress syndrome is diagnosed. She is intubated and started on mechanical ventilation in the assist/control mode at a rate of 12/min, tidal volume of 300 mL, positive end-expiratory pressure (PEEP) of 5 cm H2O, and FIO2 of 1.0. An arterial blood gas study on these settings shows a pH of 7.47, PCO2 of 30 mm Hg (4.0 kPa), and PO2 of 45 mm Hg (6.0 kPa). Peak airway pressure is 26 cm H2O, and the plateau pressure is 24 cm H2O.

46. Which of the following is the most appropriate treatment to improve this patient’s oxygenation?
Increase PEEP to 10 cm H2O
Increase respiratory rate to 18/min
Increase tidal volume to 500 ml
Start inhaled nitric oxide

47. PEEP in ARDS
Increases FRC (volume of air remaining in lungs following a normal tidal exhalation) – recruits “recruitable” alveoli, increases surface area for gas exchange
Decreases shunt, improves V/Q matching
No consensus on optimal level of PEEP

48. ALVEOLI trial High PEEP vs. low PEEP
NEJM 2004; 351:
High PEEP vs. low PEEP
Low tidal volume for all (6 ml/kg predicted weight)
Higher PEEP patients had better oxygenation, but no difference in mortality, duration of mechanical ventilation, duration of non-pulmonary organ failure
No benefit from recruitment maneuvers (CPAP cm H20 for 30 seconds) – but other studies suggest that recruitment maneuvers do help

49. Prone Positioning
Thought to improve oxygenation and respiratory mechanics by:
alveolar recruitment
redistribution of ventilation toward dorsal areas resulting in improved V/Q matching
elimination of compression of the lungs by the heart
reduction of parenchymal lung stress and strain

50. Prone Positioning
Several studies demonstrate improved oxygenation, but no overall reduction in mortality
Greatest benefit of prone positioning occurs in the sickest patients if used early after the diagnosis of ARDS

51. Other modalities - None of these have proven superior to more standard techniques
APRV
High-frequency ventilation
Partial liquid ventilation
Inverse ratio ventilation
ECMO
Nitric Oxide, prostacyclin
Ketoconazole, ibuprofen
Glutathione (anti-oxidant)
Surfactant
Steroids
Intravenous beta-agonists (increases clearance of alveolar edema) – needs more study

52. APRV

53. Pharmacotherapy - Nitric Oxide
Selectively dilates vessels that perfuse better ventilated lung zones, resulting in improved V/Q matching, improved oxygenation, reduction of pulmonary hypertension
Less benefit in septic patients
No clear improvement in mortality

54. Pharmacotherapy - Surfactant
First tried in 1980’s
No benefit in adult population
One study did demonstrate improvement in oxygenation and mortality in children

55. Pharmacotherapy - Steroids
No consensus on effectiveness – no clear benefit, some risks
ARDSnet - NEJM 2006; 354: some benefit in subgroups, but not overall; increased mortality if started after 14 days; neuromyopathy
Meduri - Chest 2007; 131: improvement in pulmonary and extrapulmonary organ dysfunction, reduction in duration of mechanical ventilation and ICU length of stay – (small sample size, imbalance in treatment arms)

56. Fluid management in ARDS
Increased extravascular lung water associated with poor outcome
Reduction in PCWP associated with increased survival

57. Fluid and Catheter Treatment Trial (FACTT)
NEJM 2006
Liberal vs conservative fluid management
CVP just as good as PCWP
Conservative management group did better (more ventilator free days, fewer ICU days, trend toward lower mortality)
No difference in incidence of hypotension or need for renal replacement therapy
Excluded patients with shock, was initiated later in ICU course (mean time 43 hrs) – early aggressive fluid resuscitation appropriate
Liberal group gained ~1 liter/day, conservative had net zero balance over 1st 7 days

58. (Target CVP <4 or PCWP <8)
Simplified Algorithm for Conservative Fluid Management
(Target CVP <4 or PCWP <8)
MAP > 60, no vasopressors for > 12 hrs
CVP PCWP Average urine output <0.5 cc/kg/hr Average urine output >0.5 cc/kg/hr
>8 >12 Lasix; reassess in 1 hr Lasix; reassess in 4 hrs
Rapid fluid bolus; reassess 1 hr Lasix; reassess in 4 hrs
<4 <8 Rapid fluid bolus; reassess 1 hr No intervention; reassess in 4 hrs

59. Supportive Care Treat predisposing factors Prophylaxis for GI bleeding
DVT prophylaxis
Prevent and treat nosocomial pneumonia – most important causes are microaspiration, biofilm formation (VAP bundle?)
Nutritional support
Blood sugar control
?Transfusion (Hgb >7 adequate)
Decrease oxygen utilization
- antipyretics, sedatives, paralysis

60. VAP Bundle – ?truly evidence based
Elevate head of bed (helpful)
Daily sedation vacation and assessment of readiness to extubate (shorter duration on vent, should be less pneumonia)
Daily chlorhexidine mouth rinse (questionable benefit)
PPI or H2 antagonists (can increase risk)
DVT prophylaxis (nothing to do with pneumonia)
Potentially helpful: subglottic suctioning, lateral head-down positioning, silver-coated ET tubes, “mucus shaver”

61. “There is nothing so useless as doing efficiently that which should not be done at all.” (Peter Drucker)

62. Question 4
A 50-year-old man is evaluated in the intensive care unit for acute respiratory distress syndrome secondary to severe community-acquired pneumonia. He is intubated and placed on mechanical ventilation. He was previously healthy and took no medications before his hospitalization.
On physical examination, temperature is 38.3 °C (100.9 °F), blood pressure is 120/60 mm Hg, and pulse rate is 110/min. The patient weighs 60.0 kg (132.3 lb); ideal body weight is 60.0 kg (132.3 lb). He is sedated and is not using accessory muscles to breathe. Central venous pressure is 8 cm H2O. Other than tachycardia, cardiac examination is normal. There are bilateral inspiratory crackles.
Initial ventilator settings are volume control with a rate of 18/min, a tidal volume of 360 mL, positive end-expiratory pressure (PEEP) of 10 cm H2O, an FIO2 of 0.8, a peak pressure of 34 cm H2O, and a plateau pressure of 32 cm H2O. Oxygen saturation by pulse oximetry is 96%.

63. Which of the following is the most appropriate next step in management?
Decrease respiratory rate
Decrease tidal volume
Increase FiO2
Increase PEEP

67. Simplified Algorithm for Conservative Fluid Management
Shock No Shock
CVP
Oliguric Non-Oliguric
>9 Vasopressor Diuretic Diuretic
4-8 Fluid bolus Fluid bolus Diuretic
<4 Fluid bolus Fluid bolus KVO fluid

68. Flow diagram for the evaluation of hypoxemia
PVO2 = mixed venous pO2
VO2 = oxygen consumption
DO2 = oxygen delivery

69. Flow diagram for the evaluation of hypercapnia
VCO2 = CO2 production