ARDS and Ventilator
Management
Behrouz Jafari, M.D.
Pulmonary & Critical Care Section
University of California-Irvine/VA Long Beach
27-year-old woman with dyspnea
• 4 days s/p C-section
• Gradual increase in dyspnea over 24
hours with fever of 101
• Evaluation
– Crackles R > L
– No peripheral edema
– Hypoxia (7.25/67/41 on 40% VM)
– Normal Echo
27-year-old woman with dyspnea
• Clinical Course
– FiO2 100%; PEEP 20 cm H2O
– Peak and plateau airway pressures: 40s
27-year-old woman with dyspnea
• Clinical Course
– FiO2 100%; PEEP 20 cm H2O
– Peak and plateau airway pressures: 40s
• Key questions
– What is the cause of acute respiratory
failure?
– How to oxygenate the patient?
– How to save her life?
Common Causes of Hypoxemic Respiratory
Failure
Acute lung injury (ALI) / ARDS
Pulmonary Edema
Diffuse alveolar Hemorrhage
Pulmonary Embolism
Interstitial lung disease
Pneumonia
Neoplasm
Pulmonary contusion
Atelectasis
COPD
Asthma
Bronchiolitis
ARDS: Berlin Definition
Category
Timing
Criterion
Within 1 week of clinical insult or
new/worsening respiratory sx
Bilateral opacities – not fully explained
Chest Imaging
by effusions, lobar/lung collapse, or
nodules
Origin of edema
Not fully explained by cardiac failure or
fluid overload. Objective measure to
rule out hydrostatic edema
Oxygenation: Mild 200 mm Hg < PaO2/FIO2 < 300 mm
Hg*
Oxygenation:
100 mm Hg < PaO2/FIO2 < 200 mm
Moderate
Hg**
Oxygenation:
PaO2/FIO2 < 100 mm Hg**
Severe
JAMA 2012;307:2526-33
* PEEP or CPAP > 5 cm H2O; ** PEEP
> 5 cm H2O
• Diffuse bilateral
infiltrates
– Patchy, confluent
– Alveolar, ground-‐glass
• In contrast to CHF,
no prominence of..
– Cardiomegaly
– Pleural effusion
– Widened vascular
pedicle
ARDS: Chest Radiograph Criteria
• Radiographic findings not attributable
to:
– Chronic changes
– Atelectasis
– Mass
– Pleural effusion
Lung Compliance in ARDS
Volume
Normal
ARDS
Pressure
ARDS Triggers
- primary vs secondary
•
Primary - Direct lung injury (eg aspiration,
•
pneumonia, contusion, inhalation)
– Patchy
– If it doesn’t evolve into SIRS/MODS,
Outcome better than secondary
ARDS Triggers
- primary vs secondary
•
•
Secondary - Lung is one of many organs
involved in SIRS/MODS (sepsis, pancreatitis,
hypotension)
– Diffuse
– Outcome worse than primary
ARDS - clinical progression
STAGE
I
DAYS
XRAY
Initiation
Nl
PATHOLOGY
PMNs
ARDS - clinical progression
STAGE
DAYS
XRAY
I
Initiation
Nl
II
1-2
days
Patchy
PATHOLOGY
PMNs
PMNs, edema, Type I
ARDS - clinical progression
STAGE
DAYS
XRAY
I
Initiation
Nl
II
1-2
days
Patchy
III 2-10
days
Diffuse
PATHOLOGY
PMNs
PMNs, edema, Type I
cell damage
Exudate, Type II
ARDS - clinical progression
STAGE
DAYS
XRAY
PATHOLOGY
I
Initiation
Nl
II
1-2
days
Patchy
III 2-10
days
Diffuse
cell damage
Exudate, Type II
IV >10
days
Diffuse
proliferation Lymph,
PMNs
PMNs, edema, Type I
fibrosis
ARDS Mortality Trend
ARDS Management
ARDS: Blocking the trigger
•Appropriate infection management
–Antibiotics
–Surgical drainage
–Foreign body removal
ARDS - mediator modulation
•Failed trials
•Coagulation cascade
•Immuno-nutrition
ARDS - blocking manifestations
•Goals are to “buy time” and avoid complications
•Support gas exchange/lung protective ventilator strategies
•Assure other components of DO2 are optimal
•Altering lung fluid fluxes
ARDS Management
Mechanical Ventilation :
• Low TV (ARDSNET
protocol)
• Unconventional
approach:
• APRV
• HFV
ARDS Management
Mechanical Ventilation :
• Low TV (ARDSNET
protocol)
General Measures:
• Prone positioning
• Nitric oxide
• Unconventional
approach:
• APRV
• HFV
• NMBA
• Fluid Management
• ECMO
Ventilator
Management
Ventilation with Lower Tidal Volumes as Compared
with Traditional Tidal Volumes for Acute Lung
Injury and Acute Respiratory Distress Syndrome
861 Patients
12 cc/kg
6 cc/kg
432 Patients
429 Patients
ARDSNET N Engl J Med 2000;342:1301-8
ARDSNET: Setting the Ventilator
FiO2
.3 .4 .4 .5 .5 .6
PEEP 5
5
8
.7
.7
.7
.8
.9
.9
.9
1
1
8 10 10 10 12 14 14 14 16 18 18 2024
http://hedwig.mgh.harvard.edu/ardsnet_old/justvent911/justvent911.html
Hypothesis of ARDSnet 6 vs 12 Trial
Brower et al, AJRCCM 2002;166:1515-17
Brower et al, AJRCCM 2005;172:1241-5
General
Measures
Effect of Prone Positioning on
Oxygenation
Gattinoni, et al. N Engl J Med 2001; 345:568-573
prone
supine
Change in PaO2:FiO2 from baseline to 1h to end of period to next morning
• Multicenter RCT comparing prone (n = 237) and supine (n
= 229) positioning in severe (P/F <150) ARDS
• Multicenter RCT comparing prone (n = 237) and supine (n
= 229) positioning in severe (P/F <150) ARDS
–
> 16 hr / d prone positioning
•Prone positioning associated with:
–
–
–
–
Lower 28 and 90 day mortality
More patients extubated at 90 days
More ventilator-free days (at 28, 90 d)
No difference in complications
Guerin et al. N Engl J Med 2013
Inhaled Nitric Oxide
• Endogenous vasodilator
• Inhalation of 2 - 40 ppm
produces selective dilation of
pulmonary vessels
• Rapidly inactivated by
combining with hemoglobin and
by oxidation
What is the Role for Nitric Oxide in
ARDS?
• Oxygenation benefit for up to 4 days (5-‐20ppm)
• No outcome benefit (survival, duration of mechanical
ventilation, ICU LOS)
• Routine use of inhaled NO is not supported
• Potential role for inhaled NO as rescue therapy for severe
refractory hypoxemia
ECMO for ARDS
• Venovenous (VV-‐
ECMO) for respiratory
failure
– Blood removed and
pumped through
oxygenator and
returned to circulation;
no cardiac support
– Large vascular
cannula, and
coagulation, infection
risk
The Bottom Line
• Identify ARDS using conventional parameters
(predisposition / timing, CXR, ABG)
• Use “lung protective approach” – 6 ml/kg
PBW Vt
• Avoid trans-alveolar pressure > 30 cmH2O;
• Avoid cyclic alveolar collapse by applying
PEEP, particularly for severe ARDS
The Bottom Line
• Conservative fluid management: aim for balanced
I=O
• Consider NMBA, prone positioning, NO, or ECMO
for severe hypoxemia – moving from least invasive
to most invasive.
• Prove that it helps to continue rx
•Randomized, blinded controlled trial of
methylprednisilone vs. placebo for ALI
persisting > 7 days
•2 mg/kg/day x 14 days; then 1 mg/kg/day x
7 days then tapered over 4 days.
Methylprednisilone vs. placebo results
Pressure vs Volume-‐Targeted Ventilation
in ARDS?
• No large, recent (low Vt) RCTs comparing only
pressure vs volume-‐targeting
• Potential advantages of pressure-‐targeting
– Easily adjust inspiratory time
– Better patient-‐ventilator synchrony
– Avoid regionally excessive transalveolar pressure
• Potential advantages of volume-‐targeting
– Avoid high tidal volume, simplify implementation
MacIntyre & Sessler. Respir Care 2010; 55:43-55
Marini & MacIntyre Chest 2011; 140:286-294
Mortality according to % of recruitable lung
RM Techniques
CCM 2004:32:2371
Mechanical Ventilation in ARDS: Prolonged
Inspiratory Time
• Methods
– Inspiratory Pause
– Decreased PIFR
– Prolonged TI
• Potential benefits
– Higher mean pressure
– Autopeep
Mechanical Ventilation in ARDS: Prolonged
Inspiratory Time
• Impaired DO2
• Barotrauma
• Need for heavy sedation
• Doesn’t work
Extended Inspiratory
Time and
Oxygenation in ARDS
Mercat A. et al., Crit Care Med 2001; 29:40
Ventilation with Lower Tidal Volumes as Compared
with Traditional Tidal Volumes for Acute Lung
Injury and Acute Respiratory Distress Syndrome
Male IBW = 50 + 2.3(ht(in) - 60)
Female IBW = 45.5 + 2.3(ht(in) - 60)
ARDSNET N Engl J Med 2000;342:1301-8
ARDSNET: Setting the Ventilator:
Subtleties
• RR can be increased to correct pH
• VT can be increased for
– Dyspnea and breath stacking (if PPl < 30)
– PPl < 25 and VT < 6 ml/kg
• VT may go as far as 4 ml/kg if needed to
keep PPl <30 cmH20
• Paralysis rarely needed (~6%)
• Vast majority complied with protocol
http://hedwig.mgh.harvard.edu/ardsnet_old/justvent911/justvent911.html
Eisner MD et al., Am J Resp Crit Care Med 2001; 164:225
Causes of Death in ARDS (%)
n=67
35
30
25
20
15
10
5
0
*
MOF/
Sepsis
Resp
Card
Neur
Heme
Ferring M, Vincent JL. Eur Respir J 1997; 10:1297-1300
Ca
Mortality (%)
ARDS: Organ Failure(s) and Mortality
100
80
60
40
20
0
0
1
2
3
Ferring M, Vincent JL. Eur Respir J 1997; 10:1297-1300
4
5
Inflammatory Cytokines in ARDS (D1)
Survivors
Nonsurvivors
pg/mL
20
15
10
5
0
TNF
IL-1
Headley et al., Chest 1997; 111:1306
IL-8
PFT's > 1 year after ARDS
110
n=16
100
90
80
70
60
FVC
Elliot, C.G. et al., ARRD 1987; 135:634
TLC
DLCO
PFT's In ARDS Survivors
90
80
70
60
FVC
50
TLC
40
DLCO
0
3
6
9
Months After Extubation
McHugh, L.G. et al., AJRCCM 1994; 150:90-94
12
ARDS: AECC Consensus Definition
Criticism
•Problems with the definition:
–PEEP not specified
–CXR criteria vague
• ALI vs ARDS: Does it matter?
ALI vs ARDS: Does it Matter?
Characteristic
ALI (n=66) ARDS (n=221)
P/F
239.8 ± 27.1 130.7 ± 37.5
Age
55.0 ± 19.8
61.3 ± 16.5
APACHE II
17.2 ± 7.9
19.2 ± 7.9
Quadrants on CXR
2.8 ± 0.8
3.0 ± 0.9
Mortality (90 d)
42.2%
41.2%
Lure, O.R. et al., Am J Respir Crit Care Med 1999; 159:1849
Lung protection tradeoffs:
PO2
Crs also better in the HIGH Vt group
Lung protection tradeoffs: pH
ARDSnet rules allowed pH values as low as 7.15
Unconventional vent.
approach
ARDS
–Unconventional approaches:
•Long I time strategies (APRV)
•HFOV
APRV
APRV Concerns:
AutoPEEP & Tidal Volume Creep
pressure
flow
Tidal volume
700
650
600
550
500
450
400 6 ml/kg IBW
350
300
10pm 2am 6am 10am
Incomplete emptying (i.e. autoPEEP)
HFOV – CPAP with a “wiggle”
HFOV for Severe ARDS
• Multicenter RCT of 548
patients of HFOV vs LTVV (Vt 6
ml/kg, high PEEP) for ARDS
(PaO2:FiO2 < 200
mmHg)
• Stopped early for harm
• HFOV associated with:
– Higher mortality (ICU, hosp)
– More sedation, NMBA
– More vasopressors
– Less refractory hypoxemia
Ferguson et al. N Engl J
Med 2013
HFOV for Severe ARDS
• Multicenter RCT of 548
patients of HFOV vs LTVV (Vt 6
ml/kg, high PEEP) for ARDS
(PaO2:FiO2 < 200
mmHg)
•• Multicenter RCT of 795 UK
patients of HFOV vs usual care
for ARDS (PaO2:FiO2 < 200
mmHg)
• –
Vt = 8.3 ml/kg, PEEP 11 cm
H2O
• Stopped early for harm
• No difference in:
• HFOV associated with:
– 30 day all cause mortality
– Higher mortality (ICU, hosp)
– ICU, Hosp LOS
– More sedation, NMBA
– Vent-‐free days
– More vasopressors
– Less refractory hypoxemia
Ferguson et al. N Engl J
Med 2013
Young et al. N Engl J Med
2013
ECMO for ARDS
• Extracorporeal Life Support (ECLS)
• Large RCT in UK :
• lower mortality and/or disability in
group (but many other Rx differences)
Peek et al. Lancet 2009
What PEEP should we
choose?
High or Low?
Pressure vs Volume-‐Targeted Ventilation
in ARDS?
• No large, recent (low Vt) RCTs comparing only
pressure vs volume-‐targeting
• Potential advantages of pressure-‐targeting
– Easily adjust inspiratory time
– Better patient-‐ventilator synchrony
– Avoid regionally excessive transalveolar pressure
• Potential advantages of volume-‐targeting
– Avoid high tidal volume, simplify implementation
MacIntyre & Sessler. Respir Care 2010; 55:43-55
Marini & MacIntyre Chest 2011; 140:286-294
ARDS outcome
•Long term mortality depends on underlying
health status (11% mortality in 1st year)
NEJM 2003; 348: 8
ARDS outcome
•Long term mortality depends on underlying
health status (11% mortality in 1st year)
•At one year:
– 6 MW 49%, VC 85%, DLCO 72%
– PTSD like syndrome
–Are these long term effects of
hypoxemia? hypotension? drugs ?
NEJM 2003; 348: 8
Controversies in VILI Overdistention
•Is it “maximal” stretch or “tidal” stretch (or
both) that causes VILI?
–If “maximal” , goal is to keep Pplat <30 with
any VT
•Pplat < 30 is “safe”
–If “tidal”, goal is to reduce VT and Pplat to
minimums
•No Pplat is “safe”
Stretch injury - Is it max
stretch or tidal stretch?
Controversies in VILI - Overdistention
•Is it “maximal” stretch or “tidal” stretch (or both)
that causes VILI?
–If “maximal” , goal is to keep Pplat <30 with any
VT
•Pplat < 30 is “safe”
–If “tidal”, goal is to reduce VT and Pplat to
minimums
•No Pplat is “safe”
Steroids in ARDS:
• Use of low dose, longer duration steroids is
associated with more rapid recovery and
may be associated with reduced mortality
risk
– But, small studies, methodological quality
issues
Steroids in ARDS:
• Use of low dose, longer duration
steroids is associated with more rapid
recovery and may be associated with
reduced mortality risk
– But, small studies, methodological quality
issues
• If use steroids in ARDS
– Avoid starting after day 14
– Avoid NMBA
– Infection surveillance
– Methylprednisolone 2m g/kg/d, taper over 4
weeks
Lower Tidal Volumes and Survival in ARDS
ARDSNET N Engl J Med 2000;342:1301-8