ARDS and Ventilator Management Behrouz Jafari, M.D. Pulmonary & Critical Care Section University of California-Irvine/VA Long Beach

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


• Clinical Course– FiO2 100%; PEEP 20 cm H2O

– Peak and plateau airway pressures: 40s


• 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

FailureAcute lung injury (ALI) / ARDS Pulmonary EdemaDiffuse alveolar HemorrhagePulmonary EmbolismInterstitial lung diseasePneumoniaNeoplasmPulmonary contusionAtelectasisCOPDAsthmaBronchiolitis

ARDS: Berlin Definition

JAMA 2012;307:2526-33

Category CriterionTiming Within 1 week of clinical insult or

new/worsening respiratory sx

Chest Imaging Bilateral opacities – not fully explained 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: Moderate

100 mm Hg < PaO2/FIO2 < 200 mm Hg**

Oxygenation: Severe

PaO2/FIO2 < 100 mm Hg**

* PEEP or CPAP > 5 cm H2O; ** PEEP > 5 cm H2O

• Di use bilateral ffinfiltrates– Patchy, confluent– Alveolar, ground- ‐

glass

• In contrast to CHF, no prominence of..– Cardiomegaly– Pleural e usionff– Widened vascular

pedicle

ARDS: Chest Radiograph Criteria

• Radiographic findings not attributable to:– Chronic changes– Atelectasis– Mass– Pleural effusion

Lung Compliance in ARDS

Normal

ARDS

Pressure

Vol

ume

- 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 Triggers

ARDS - clinical progression

STAGE DAYS XRAY PATHOLOGY

I Initiation Nl PMNs




II 1-2 days

Patchy PMNs, edema, Type I




II 1-2 days


III 2-10 days

Diffuse cell damage Exudate, Type II




II 1-2 days


III 2-10 days

Diffuse cell damage Exudate, Type II

IV >10 days

Diffuse proliferation Lymph,

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 ManagementMechanical Ventilation :

• Low TV (ARDSNET protocol)

•Unconventional approach:

• APRV• HFV

General Measures:

•Prone positioning

•Nitric oxide

•NMBA

•Fluid Management

•ECMO

Ventilator Management

ARDSNET N Engl J Med 2000;342:1301-8

Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and Acute Respiratory Distress Syndrome

861 Patients

429 Patients432 Patients

6 cc/kg 12 cc/kg

http://hedwig.mgh.harvard.edu/ardsnet_old/justvent911/justvent911.html

ARDSNET: Setting the Ventilator

FiO2 .3 .4 .4 .5 .5 .6 .7 .7 .7 .8 .9 .9 .9 1 1

PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 18 20-24

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

Change in PaO2:FiO2 from baseline to 1h to end of period to next morning

supine

• 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

• Multicenter RCT comparing prone (n = 237) and supine (n = 229) positioning in severe (P/F <150) ARDS

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

• Impaired DO2

• Barotrauma

• Need for heavy sedation

• Doesn’t work

Mechanical Ventilation in ARDS: Prolonged Inspiratory Time

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)

http://hedwig.mgh.harvard.edu/ardsnet_old/justvent911/justvent911.html

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

Eisner MD et al., Am J Resp Crit Care Med 2001; 164:225

Ferring M, Vincent JL. Eur Respir J 1997; 10:1297-1300

Causes of Death in ARDS (%)

05

101520253035

MOF/Sepsis

Resp Card Neur Heme Ca

*

n=67

Ferring M, Vincent JL. Eur Respir J 1997; 10:1297-1300

ARDS: Organ Failure(s) and Mortality

0

20

40

60

80

100

0 1 2 3 4 5

Mor

talit

y (%

)

Headley et al., Chest 1997; 111:1306

Inflammatory Cytokines in ARDS (D1)

0

5

10

15

20

TNF IL-1 IL-8

pg/

mL

Survivors Nonsurvivors

PFT's > 1 year after ARDS

DLCOTLCFVC

Pe

rce

nt P

red

icte

d110

100

90

80

70

60

Elliot, C.G. et al., ARRD 1987; 135:634

n=16

PFT's In ARDS Survivors

Months After Extubation

129630

Pe

rce

nt P

red

icte

d90

80

70

60

50

40

FVC

TLC

DLCO

McHugh, L.G. et al., AJRCCM 1994; 150:90-94

ARDS: AECC Consensus Definition

Criticism

•Problems with the definition:

–PEEP not specified

–CXR criteria vague

•ALI vs ARDS: Does it matter?

Lure, O.R. et al., Am J Respir Crit Care Med 1999; 159:1849

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%

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

Incomplete emptying (i.e. autoPEEP)

700

650

600

550

500

450

400

350

300

10pm 2am 6am10am

Tidal volume

6 ml/kg IBW

pressure

flow

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)

• Stopped early for harm

• HFOV associated with:

– Higher mortality (ICU, hosp)– More sedation, NMBA– More vasopressors– Less refractory hypoxemia

• 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

• No di erence in:ff– 30 day all cause mortality– ICU, Hosp LOS– Vent- ‐free days

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 di erences) ffPeek 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

•Long term mortality depends on underlying health status (11% mortality in 1st year)

ARDS outcome

NEJM 2003; 348: 8

•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 ?

ARDS outcome

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

Documents

ARDS and Ventilator Management Behrouz Jafari, M.D. Pulmonary & Critical Care Section University of California-Irvine/VA Long Beach