Pediatric ARDS: Understanding It and

Managing It

Pediatric ARDS: Understanding It and

Managing ItJames D. Fortenberry, MD

Medical Director, Pediatric and Adult ECMO

Medical Director, Critical Care Medicine

Children’s Healthcare of Atlanta at Egleston

New and ImprovedNew and Improved

Adult Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome

ARDS: New Definition

Criteria Acute onset Bilateral CXR infiltrates PA pressure < 18 mm Hg Classification

Acute lung injury - PaO2 : F1O2 < 300

Acute respiratory distress syndrome - PaO2 : F1O2 < 200

- 1994 American - European Consensus Conference

Clinical Disorders Associated with ARDS

Direct Lung Injury Indirect Lung Injury

Common causes Common Causes

Pneumonia SepsisAspiration of gastriccontents

Severe trauma with shock ,multiple transfusions

Less common causes Less common causes

Pulmonary contusion Cardiopulmonary bypassFat emboli Drug overdoseNear-Drowning Acute pancreatitisI nhalational injury Transfusions of blood productsReperfusion pulmonaryedema

The Problem: Lung Injury

Etiology In Children

Other 4%

Hemorrhage 5%

Trauma 5%

Noninfectious Pneumonia 14%

Cardiac Arrest 12%

Septic Syndrome 32%

Infectious Pneumonia 28%

Davis et al., J Peds 1993;123:35

ARDS - Pathogenesis

Instigation

• Endothelial injury: increased permeability of alveolar - capillary barrier

• Epithelial injury : alveolar flood, loss of surfactant, barrier vs. infection

• Proinflammatory mechanisms

ARDS Pathogenesis

Resolution

• Equally important

• Alveolar edema - resolved by active sodium transport

• Alveolar type II cells - re-epithelialize

• Neutrophil clearance needed

ARDS - Pathophysiology

•Decreased compliance

•Alveolar edema

•Heterogenous

•“Baby Lungs”

ARDS:CT Scan View

Phases of ARDS

• Acute - exudative, inflammatory

(0 - 3 days)

• Subacute - proliferative

(4 - 10 days)

• Chronic - fibrosing alveolitis

( > 10 days)

ARDS - Outcomes

• Most studies - mortality 40% to 60%; similar for children/adults

• Death is usually due to sepsis/MODS rather than primary respiratory

• Mortality may be decreasing

53/68 % 39/36 %

ARDS - Principles of Therapy

•Provide adequate gas exchange

•Avoid secondary injury

Therapies for ARDS

Innovations:NOPLVProningSurfactantAnti-Inflammatory

Mechanical Ventilation Gentle

ventilation:

Permissive hypercapnia

Low tidal volume

Open-lung

HFOV

ECMOIVOX

IV gas exchange

AVCO2R

Total Implantable Artificial Lung

ARDS

Extrapulmonary Gas Exchange

The Dangers of Overdistention

• Repetitive shear stress

• Injury to normal alveoli

• inflammatory response

• air trapping

• Phasic volume swings: volutrauma

• compliance

• intrapulmonary shunt

• FiO2

• WOB

• inflammatory response

The Dangers of Atelectasis

0

10

20

13 33 38

Airway Pressure (cmH20)

Lun

g V

olum

e (m

l/kg)

AtelectasisAtelectasis

““Sweet Sweet Spot”Spot”

OverdistentioOverdistentionn

Lung Injury Zones

ARDS: George Bush Therapy

“Kinder, gentler” forms of ventilation:

•Low tidal volumes (6-8 vs.10-15 cc/kg)

•“Open lung”: Higher PEEP, lower PIP

•Permissive hypercapnia: tolerate higher pCO2

Lower Tidal Volumes for ARDS

0

5

10

15

20

25

30

35

40

Percent

Death

Ven

t freed

ays

Traditional Lower

*

*

* p < .001

ARDS Network,NEJM, 342: 2000

22% decrease

Is turning the ARDS patient “prone” to be

helpful?

Is turning the ARDS patient “prone” to be

helpful?

Prone Positioning in ARDS

• Theory: let gravity improve matching perfusion to better ventilated areas

• Improvement immediate

• Uncertain effect on outcome

Prone Positioning in Pediatric ARDS:Longer May Be Better

• Compared 6-10 hrs PP vs. 18-24 hrs PP

• Overall ARDS survival 79% in 40 pts.

Relvas et al., Chest 2003

Brief vs. Prolonged Prone Positioning in Children

0

5

10

15

20

25

Pre- PP Brief PP Prolonged PP

Oxygen

ati

on

In

dex

(OI)

- Relvas et al., Chest 2003

*

***

High Frequency High Frequency Oscillation:Oscillation:A Whole Lotta A Whole Lotta Shakin’ Goin’ Shakin’ Goin’ OnOn

- Reese Clark- Reese Clark

It’s not absolute pressure, but volume or

pressure swings that promote lung injury or

atelectasis.

It’s not absolute pressure, but volume or

pressure swings that promote lung injury or

atelectasis.

•Rapid rate

•Low tidal volume

•Maintain open lung

•Minimal volume swings

High Frequency Ventilation

High Frequency Oscillatory Ventilation

HFOV is the easiest way to find the ventilation

“sweet spot”

HFOV: Benefits Vs. Conventional Ventilation

0

20

40

HFOV CV CV toHFOV

HFOV toCV

Sur

viva

l wit

h CL

D%

- - Arnold et al, Arnold et al, CCMCCM, , 19941994

**

HFOV vs. CMV in Pediatric Respiratory Failure

Surfactant in ARDS

• ARDS: surfactant deficiency surfactant present is

dysfunctional

• Surfactant replacement improves physiologic function

Surfactant in Pediatric ARDS

•Current randomized multi-center trial

•Placebo vs calf lung surfactant (Infasurf)

•Children’s at Egleston is a participating center-study closed, await results

Steroids in Unresolving ARDS

• Randomized, double-blind, placebo-controlled trial

• Adult ARDS ventilated for > 7 days without improvement

• Randomized: Placebo Methylprednisolone 2 mg/kg/day x 4

days, tapered over 1 month

Meduri et al, JAMA 280:159, 1998

Steroids in Unresolving ARDS

0102030405060708090

100

ICUsurvival

Hospitalsurvival

Steroid Placebo

* *

p<.01*- Meduri et al., JAMA, 1998

Steroids in Unresolving ARDS

• Randomized, double-blind, placebo-controlled trial

• ARDSNetwork-180 adults

• Randomized: Placebo Methylprednisolone No mortality difference Decreased ventilator-free days but

only if started 7-14 daysSteinberg, NEJM, 354:1671,2006

Inhaled Nitric Oxide in Respiratory Failure

Neonates Beneficial in term neonates with

PPHN Decreased need for ECMO

Adults/Pediatrics Benefits - lowers PA pressures,

improves gas exchange Randomized trials: No difference

in mortality or days of ventilation

Inhaled NO and HFOV In Pediatric ARDS

5853

58

71

0

10

20

30

40

50

60

70

80

Sur

viva

l %

Dobyns et al., Dobyns et al.,

J PedsJ Peds, 2000, 2000

*

Partial Liquid Ventilation

Partial Liquid Ventilation

Mechanisms of action oxygen reservoir recruitment of lung volume alveolar lavage redistribution of blood flow anti-inflammatory

Liquid Ventilation

Pediatric trials started in 1996 Partial: FRC (15 - 20 cc/kg)

Study halted 1999 due to lack of benefit

Adult study (2001): no effect on outcome

ARDS- “Mechanical” Therapies

ARDS- “Mechanical” Therapies

Prone positioning - Unproven outcome benefit

Low tidal volumes - Outcome benefit in large study

Open-lung strategy - Outcome benefit in small study

HFOV -Outcome benefit in small study

ECMO - Proven in neonates unproven in children

Pharmacologic Approaches to ARDS: Randomized Trials

Glucocorticoids

Fibrosing alveolitis - lowered mortality, small study

Surfactant - possible benefit in children

Inhaled NO - no benefit

Partial liquid ventilation - no benefit

“…We must discard the old approach and continue to search for ways to improve mechanical ventilation. In the meantime, there is no substitute for the clinician standing by the ventilator…”

- Martin J. Tobin, MD