Respiratory Failure/ ARDS
Ian B. Hoffman, MD, FCCP
Pulmonary & Critical Care Medicine
September 4, 2013
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)
Which of the following is the most likely cause of this
patient’s hypoxemia?
A. Acute respiratory distress syndrome
B. E. coli pneumonia
C. Heart failure
D. Eosinophilic pneumonia
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
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
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)
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
Ventilation–perfusion (V/Q) relationships and
associated blood gas abnormalities
Shunt
The influence of shunt fraction on the relationship
between the inspired oxygen (FiO2) and the
arterial PO2 (PaO2).
Ventilatory Failure
 Failure of respiratory pump to adequately
eliminate CO2
 pCO2 :
VCO2
VA
 VCO2 determined by rate of total body
metabolism
ALVEOLAR HYPOVENTILATION IN THE ICU
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
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 24-48 hrs, then exercise
 Stop aminoglycosides
 Rule out hypothyroidism, oversedation, critical illness
myopathy/neuropathy
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
ARDS – Acute Respiratory
Distress Syndrome
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)
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)
1994 American European Consensus
Acute Lung Injury
ARDS
 Acute onset
 Acute onset
 Bilateral infiltrates c/w
 Bilateral infiltrates c/w
pulmonary edema
 No clinical evidence of
left-sided CHF (PCWP
<18)
pulmonary edema
 No clinical evidence of
left-sided CHF (PCWP
<18)
 paO2/FiO2 ratio <300
 paO2/FiO2 ratio <200
100/0.40 = 250
100/0.60 = 167
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
Severity of ARDS (2012)
ARDS Severity
PaO2/FiO2
(on PEEP 5)
Mortality
Mild
200 - 300
27%
Moderate
100 - 200
32%
Severe
<100
45%
ARDS - Incidence
 Annual incidence 75 per 100,000 (1977)
 9% of American critical care beds occupied
by pts with ARDS
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
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
ARDS - Causes
 Direct Lung Injury
 Pneumonia
 Gastric aspiration

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
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Lung contusion
Fat emboli
Near drowning
Inhalation injury
Reperfusion injury
 Indirect Lung Injury
 Sepsis
 Multiple trauma

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Cardiopulm bypass
Drug overdose
Acute pancreatitis
Blood transfusion
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
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
ARDS – Course
 Early
 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
ARDS - Complications
 Ventilator induced lung injury
 Sedation and neuromuscular blockade
 Nosocomial infection
 Pulmonary emboli
 Multiple organ dysfunction
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)
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.
Which of the following is the most appropriate tidal
volume?
A. 300 ml
B. 450 ml
C. 700 ml
D. 840 ml
Ventilatory Goals in ARDS
 Provide adequate oxygenation without
causing damage related to:



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Oxygen toxicity
Hemodynamic compromise
Barotrauma
Alveolar overdistension
Alveolar shear
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
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
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
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
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
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.
ARDS Network Trial
NEJM 2000; 342:1301-1308.
 Initial tidal volume of 6 ml/kg IBW and plateau
pressure <30
vs.
Initial tidal volume of 12 ml/kg IBW and
plateau pressure <50
 Reduction in mortality of 22% (31% vs 40%)
Ventilator management in patients with acute respiratory distress syndrome or acute lung injury
N Engl J Med 2000; 342:1301
Question 3
A 25-year-old woman is admitted to the intensive care unit (ICU) for a 6hour 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.
Which of the following is the most appropriate
treatment to improve this patient’s oxygenation?
A. Increase PEEP to 10 cm H2O
B. Increase respiratory rate to 18/min
C. Increase tidal volume to 500 ml
D. Start inhaled nitric oxide
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
ALVEOLI trial
NEJM 2004; 351:327-336.
 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 35-40
cm H20 for 30 seconds) – but other studies suggest
that recruitment maneuvers do help
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
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
Other modalities - None of these have proven
superior to more standard techniques

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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
APRV
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
Pharmacotherapy - Surfactant
 First tried in 1980’s
 No benefit in adult population
 One study did demonstrate improvement in
oxygenation and mortality in children
Pharmacotherapy - Steroids
 No consensus on effectiveness – no clear
benefit, some risks
 ARDSnet - NEJM 2006; 354:1671-1684.
some benefit in subgroups, but not overall;
increased mortality if started after 14 days;
neuromyopathy
 Meduri - Chest 2007; 131:954-963.
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)
Fluid management in ARDS
 Increased extravascular lung water
associated with poor outcome
 Reduction in PCWP associated with
increased survival
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
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
4-8
8-12
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
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
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 headdown positioning, silver-coated ET tubes, “mucus
shaver”
“There is nothing so useless as doing
efficiently that which should not be
done at all.” (Peter Drucker)
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%.
Which of the following is the most appropriate
next step in management?
A. Decrease respiratory rate
B. Decrease tidal volume
C. Increase FiO2
D. Increase PEEP
Simplified Algorithm for Conservative Fluid Management
Shock
CVP
No Shock
Oliguric
Non-Oliguric
>9
Vasopressor
Diuretic
Diuretic
4-8
Fluid bolus
Fluid bolus
Diuretic
<4
Fluid bolus
Fluid bolus
KVO fluid
Flow diagram for the evaluation of
hypoxemia
PVO2 = mixed venous pO2
VO2 = oxygen consumption
DO2 = oxygen delivery
Flow diagram for the evaluation of
hypercapnia
VCO2 = CO2 production