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MELBOURNE

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Mechanical ventilation strategies in acute hypoxic respiratory failure

Redefining ALI / ARDS in children Why we need the “P” in PARDS

Dr Simon Erickson Paediatric Intensive Care Princess Margaret Hospital

Clinical syndrome characterized by diffuse inflammation in the lung

Results in significant hypoxemia from endothelial injury to the pulmonary vasculature and alveolar epithelial injury

No definitive diagnostic test (i.e. biomarker) which is present in all cases (even histopathology inconsistent)

Hypoxemia (Shunt) Poor Respiratory System Compliance Decreased End Expiratory Lung Volumes

(FRC) Diffuse Process Endothelial Injury Edema Increased alveolar dead space

• Population estimates 1.4-9.5/100,000/yr • 1-4% of all PICU admissions have ALI • Mechanically Ventilated Children (>12-24h) ARDS: 2-7% ALI: 6-10%

• LRTI most common trigger • Indirect Lung Injury from Sepsis also common, with worse prognosis

Randolph 2009, 2003, Farias 2004, Dahlem 2003, Erickson 2007, Curley 2005, Willson 2005

•Mortality between 30-40% for adults and 8-30% for children with ALI or ARDS •RCTs: 8% (prone); 28% (Calfactant –with BMT); 14% (Calfactant-no BMT)

Is there any evidence to guide us?

How are we doing currently?

Courtesy S. Watson, PALICC

Zimmerman et al, Pediatrics 2009

AECC Definition AECC Limitations

Timing Acute onset No definition of acute

ALI category All patients with PaO2/FiO2<300 Misinterpreted as PaO2/FiO2 201-300

leading to the confusing ALI/ARDS term

Oxygenation PaO2/FiO2 ≤ 300 mmHg (regardless of PEEP)

Effect of PEEP and FiO2 on PaO2/FiO2 ; difficulty in estimating FiO2 in non-intubated patients

Chest Radiograph Bilateral infiltrates seen on frontal chest radiograph

Poor interobserver reliability of chest radiograph interpretation

PAWP PAWP ≤ 18 mmHg when measured or no clinical evidence of left atrial hypertension

High PAWP and ARDS may coexist

Poor interobserver reliability of PAWP and clinical assesments of left atrial hypertension

Risk Factor None Not formally included in definition

Phua: CCM 2008; Wheeler: NEJM; 2006; Villar: AJRCCM 2007;Meade: AJRCCM 2000; Rubenfeld Chest 1999; Komadina: Chest 1991;

Acute Respiratory Distress Syndrome

Timing Within 1 week of a known clinical insult or new/worsening respiratory symptoms

Origin of Edema Respiratory failure not fully explained by cardiac failure or fluid overload;

Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present

Mild Moderate Severe

Oxygenation b 200<PaO2/FiO2< 300

with PEEP or CPAP ≥ 5 cmH2O

100<PaO2/FiO2<200 with

PEEP ≥ 5 cmH2O

PaO2/FiO2<100 with

PEEP ≥ 10 cmH2O

Chest Imaging a Bilateral opacities - not fully explained by effusions, lobar

collapse, masses

Bilateral opacities - not fully explained by effusions, lobar

collapse, masses Opacities involving ≥3 quadrants

Ancillary Physiology N/A N/A VE, CORR ≥ 10 L/min d, f

or CRS ≤ 40 mL/cmH2O e, f

eSUPPLEMENT

1) Include radiographs of consensus interpretations for qualifying opacities vs not vs equivocal

2) Include case vignettes on how to assess “not fully explained by cardiac failure of fluid overload”

Pediatric Specific Definition Pathobiology and Ventilator Induced Lung

Injury Selected topics on ventilator/ancillary

management

Build off Berlin Definition- is Berlin alone Adequate? Pediatric Considerations

1. Timing (similar to adults?) 2. Age 3. Co-existence with cardiac failure/dysfunction (similar to

adults?) 4. What are best respiratory criteria for risk

stratification/disease severity 5. How do we handle patients on non-invasive ventilation

and/or those without arterial lines 6. How important/reliable are Radiographic Criteria for

Definition of ARDS 7. Defining it in patients with pre-existing cardiac or

pulmonary co-morbidities

OI = oxygenation index = (FiO2* mean airway pressure*100)/ PaO2

OSI = oxygen saturation index = (FiO2* mean airway pressure*100) /SpO2

Age Exclude patients with peri-natal related lung disease

Timing Within 7 days of known clinical insult

Origin of Edema Respiratory failure not fully explained by cardiac failure or fluid overload

Chest Imaging Chest imaging findings of new infiltrate(s) consistent with acute pulmonary parenchymal disease

Oxygenation

Non Invasive mechanical ventilation Invasive mechanical ventilation

PARDS (No severity stratification) Mild Moderate Severe

Full face-mask bi-level ventilation or CPAP ≥5 cm H20 2

PF ratio ≤ 300 SF ratio ≤ 264 1

4 ≤ OI < 8

5 ≤ OSI < 7.51

8 ≤ OI < 16

7.5 ≤ OSI < 12.31

OI ≥ 16

OSI ≥ 12.31

Special Populations

Cyanotic Heart Disease

Standard Criteria above for age, timing, origin of edema and chest imaging with an acute deterioration in oxygenation not explained by underlying cardiac disease. 3

Chronic Lung Disease

Standard Criteria above for age, timing, and origin of edema with chest imaging consistent with new infiltrate and acute deterioration in oxygenation from baseline which meet oxygenation criteria above.3

Left Ventricular dysfunction

Standard Criteria for age, timing and origin of edema with chest imaging changes consistent with new infiltrate and acute deterioration in oxygenation which meet criteria above not explained by left ventricular dysfunction.

Can we define paediatric? Perinatal causes?

Post-natal alveolar growth may continue until adult height achieved

Post-natal lung morphogenesis and immune development likely to affect responses

Exclusions IRDS

Perinatal lung injury

Congenital abnormalities

Epidemiology of Risk Factors Different

ANZ study 2007

Mortality or Length of Ventilation not different in most studies, not all

Upper limit?

Table 3. CDC age-adjusted mortality per 100,000

persons from sepsis and influenza and

pneumonia in the United States in 2009

Age (years) Sepsis Influenza and

Pneumonia

< 1 5.2 5.9

1 - 4 0.4 0.9

5 - 14 0.2 0.6

15 - 24 0.3 1

25 - 34 0.9 1.9

35 - 44 2.2 3.2

45 - 54 5.5 6.5

55 - 64 13.3 11.9

65 - 74 32 30.1

75 - 84 78.4 105.9

≥ 85 173.8 413.5

Zimmerman 2009, Flori 2005, Dahlem 2003, Erickson 2007, Ghuman 2012, Smith 2013

PF ratio versus OI

OI=(FiO2* mean airway pressure*100)/ PaO2

Variable ventilator management and in particular lower PEEP use in Pediatrics compared to Adults

Need to control for ventilator support

More Frequent use of HFOV

PEEP 5 cmH20

PaO2 = 60, FiO2=0.6, MAP = 8

PF Ratio 100

OI =8

PEEP 14 cmH20

PaO2 = 120, FiO2=0.5, MAP = 19

PF Ratio 240

OI = 8

OI versus PF ratio

* > 50% of patients with PEEP ≤5 cmH20

> 50% of adults in ARDSNet studies on PEEP

≥10cmH20 at study inclusion (Britos CCM)

Study PEEP

Flori 2005 5.3 +/- 2.6

Erikson 2007 8.5 (7,11)

Khemani 2009 6 (4,8)

Santishi 2010 (PALIVE)* 6.9 +/- 2.7

Lopez-Fernandez 2012 8.9 +/- 2.9

Variable PEEP use in Pediatrics

Santichi PALIVE 2011

Newth CPCCRN 2014

Oscillate NEJM 2013

OI >16 8-16 4-8 <4 Total

Category Severe Moderate Mild At Risk

Derivation Set

Khemani 2009

Number 98 (24.7%) 104 (26.2%) 147 (37.1%) 48 (12.1%) 397

Mortality 40 (40.8%) 21 (20.2%) 23 (11.6%) 2 (4.2%) 80 (20.2%)

Validation Set

Flori 2005

Number 28 (16.4%) 60 (35.1%) 67 (39.2%) 16 (9.4%) 171

Mortality 10 (35.5%) 16 (26.7%) 13 (19.4%) 1 (6.25%) 40 (23.4%)

Curley 2005

Number 34 (40%) 28 (33%) 20 (24%) 3 (3%) 85

Mortality 2 (5.9%) 4 (14.3%) 1 (5%) 0 (0%) 7 (8.2%)

Erickson 2007

Number 38 (33.3%) 31 (27.2%) 36 (31.6%) 9 (7.9%) 114

Mortality 20 (52.6%) 10 (32.3 %) 5 (13.9%) 0 (0%) 35 (30.7%)

Kneyber 2008

Number 8 (27.6%) 11 (37.9%) 10 (34.5%) 0 (0%) 29

Mortality 1 (12.5%) 3 (27.3%) 1 (10%) 0 (0%) 5 (17.3%)

Lopez-Fernandez 2012

Number 72 (55%) 47 (35.9%) 12 (9.1%) 0 (0%) 131

Mortality 24 (33.3%) 10 (21.3%) 3 (25%) 0(0%) 37 (28.2%)

Sapru 2013

Number 47 (28%) 68 (40.2%) 40 (23.7%) 14 (8.3%) 169

Mortality 9 (19.1%) 11 (16.2%) 0 (0%) 0 (0%) 20 (11.9%)

Validation Set Total

Number 225 (32.7%) 241 (34.8%) 184 (26.6%) 42 (6.1%) 692

Mortality 66 (29.3%) 54 (22.4%) 23 (12.5%) 1 (2.4%) 144 (20.8%)

1.5.1 Oxygenation Index [OI=(FiO2* mean airway pressure*100)/ PaO2], in preference to PaO2/FiO2 (PF) ratio, should be the primary metric of lung disease severity to define P-ARDS for all patients treated with invasive mechanical ventilation. Strong agreement

1.5.2 PaO2/FiO2 (PF) ratio should be used to diagnose ARDS for patients receiving non‐invasive full face mask ventilation (CPAP or BiPAP) with a minimum CPAP of 5 cm H2O. Strong agreement

Critical Care Medicine 2012

Requiring PF ratio selects for patients with hypoxemia and cardiovascular dysfunction

Not using pulse oximetry criteria underestimates the prevalence

of ARDS and over-estimates mortality, by selecting for a more ill

patient population

1.8.1 To apply SpO2 criteria to diagnose P-ARDS, oxygen therapy should be titrated to achieve an SpO2 between 88- 97%. Strong agreement

1.6.1 Oxygen Saturation Index [OSI =(FiO2* mean airway pressure*100)/SpO2]should be used when an OI is not available for stratification of risk for patients receiving invasive mechanical ventilation. Strong agreement

1.6.2 SF (SpO2/FiO2)ratio can be used when PF

ratio is not available to diagnose P-ARDS in patients receiving non‐invasive full face mask ventilation (CPAP or BiPAP) with a minimum CPAP of 5 cm H2O. Strong agreement

Left ventricular failure AECC vs. Berlin

Assessment of LV function

Common complication

Children with LV dysfunction that fulfill all other PARDS criteria where hypoxaemia and CXR changes cannot be explained by LV failure/fluid overload alone

OI 5.6 OI 18

Cyanotic congenital heart disease Very little data

Generally been considered an exclusion

CCHD at high risk

Role of echo to exclude cardiac changes

CCHD patients considered to have P-ARDS if acute deterioration in oxygenation, CXR changes, known insult not explained by underlying cardiac disease

Chronic lung disease At risk

Common underlying CLD (10-35%)

Includes dependence on supplemental O2, NIV, tracheostomy

P-ARDS requires known insult, acute CXR changes, acute worsening hypoxia

Increasing use in children with ARDS Immunocompromised and

chronic neurological disease

Reduced need for sedation

May reduce overall need for intubation

For non-invasive bi-level ventilation or CPAP ≥5 cm H20 If PaO2 available, then PF

ratio ≤ 300

If PaO2 not available, wean FiO2 to maintain SpO2 ≤ 97%, SF ratio ≤ 264

What is the sensitivity of CXR changes for Diffuse Alveolar Disease?

Sensitivity low (60-70%)

Correlation between CXR and CT poor

Timing lag

What is the inter-observer variability of CXR?

Significant (Angoulvant et al, Pediatr Pulmonol 2008)

Can ARDS exist with unilateral CXR changes? Does the presence of unilateral vs bilateral CXR

changes assist risk stratification?

Conflicting adult evidence

Paediatric data

Parvathaneni ATS 2016

Tidal volume and its effect on outcome Ventilatory strategies Ancillary treatments

Initial Vt and Mortalityn=398

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Survived Died Mortality

Day 1 Vt and Mortalityn=376

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Day 2 Vt and Mortalityn=343

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ICM 2009

Age < 1 year Age > 1 year

Higher VT associated with improved outcome,

particularly for children < 1 year

Multitude of subgroup analysis exploring various VT cut points

No clear relationship between VT and mortality in children regardless of ARDS severity

Baseline Lung Injury Score ICM 2009

Supra physiologic VT harmful in pediatric animal models, but younger animals less susceptible than older animals to VILI

Relatively more surfactant production in pediatric versus adult lung with high VT

Fewer inflammatory cytokines in pediatric versus adult lung with high VT

Difference in elastin and collagen in pediatric versus adult lung

Higher endothelial injury and coagulopathy in pediatric animal models of high VT

Mode of Ventilation (set versus controlled variables) ARDSNet – volume controlled Pediatric – Pressure control - PC or PRVC (volume targeted but

decelerating flow) Developmental Differences (changes in proportion of FRC, TLC, VT)

Body weight for calculating tidal volume

Adult: predicted BW (obesity, BW calculated from height) Pediatric: actual BW (obesity & FTT, contractures; now formulae for height

from ulnar length 0 < 18 years old)

Tidal Volume (VT exhaled) Adult: measured at ventilator – use SET volume Pediatrics: should be measured at ETT (tubing compliance)

More inotropres, more NMB, more sedatives in HFOV

Guerin NEJM June 2013

Curley et al. JAMA 2005

No improvement in clinically important outcomes, stopped early for futility Very low mortality, 8%.

PF =150 OI=14-18 VT=6-8 PEEP=7-9

Disease severity - Moderate ARDS (Peds) vs. Severe (Adults)

Chest Wall compliance issues- Age effects? Optimal use of Lung protective ventilation? Adults studies only have shown benefit when good LPV

being used

High Rate of HFOV use in both arms in pediatrics

Is VILI as big of a problem in PARDS as adults? Recruitability of lung disease Higher rates of sepsis in adults (? More recruitable

lung)

1. Timing √

2. Age √

3. Co-existence with cardiac failure/dysfunction √

4. What are best respiratory criteria for risk stratification/disease severity √

5. How do we handle patients on non-invasive ventilation and/or those without arterial lines √

6. How important/reliable are Radiographic Criteria for Definition of ARDS √

7. Defining it in patients with pre-existing cardiac or pulmonary co-morbidities √

OI = oxygenation index = (FiO2* mean airway pressure*100)/ PaO2

OSI = oxygen saturation index = (FiO2* mean airway pressure*100) /SpO2

Age Exclude patients with peri-natal related lung disease

Timing Within 7 days of known clinical insult

Origin of Edema Respiratory failure not fully explained by cardiac failure or fluid overload

Chest Imaging Chest imaging findings of new infiltrate(s) consistent with acute pulmonary parenchymal disease

Oxygenation

Non Invasive mechanical ventilation Invasive mechanical ventilation

PARDS (No severity stratification) Mild Moderate Severe

Full face-mask bi-level ventilation or CPAP ≥5 cm H20 2

PF ratio ≤ 300 SF ratio ≤ 264 1

4 ≤ OI < 8

5 ≤ OSI < 7.51

8 ≤ OI < 16

7.5 ≤ OSI < 12.31

OI ≥ 16

OSI ≥ 12.31

Special Populations

Cyanotic Heart Disease

Standard Criteria above for age, timing, origin of edema and chest imaging with an acute deterioration in oxygenation not explained by underlying cardiac disease. 3

Chronic Lung Disease

Standard Criteria above for age, timing, and origin of edema with chest imaging consistent with new infiltrate and acute deterioration in oxygenation from baseline which meet oxygenation criteria above.3

Left Ventricular dysfunction

Standard Criteria for age, timing and origin of edema with chest imaging changes consistent with new infiltrate and acute deterioration in oxygenation which meet criteria above not explained by left ventricular dysfunction.