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Jan Hau Lee, MBBS, MRCPCH. MCI
Children’s Intensive Care Unit
KK Women’s and Children's Hospital,Singapore
1
Progress in Acute
Respiratory Distress
Syndrome in Pediatrics
Conflicts of Interest
2
Organizer of WFPICCS 2018 Video at the end of my presentation
Overview
• Pediatric Acute Respiratory Distress Syndrome
• Current Epidemiology
• Asia’s Experience
• Concluding Remarks
3
Acute Respiratory Distress Syndrome
4
Ashbaugh et al. Lancet 1967 Ware and Matthay. N Engl J Med 2004
Pediatric ARDS
• Relatively small percentage of total number of PICU admissions
• One of the most challenging patient populations to manage
• Lack of pediatric specific data
5
Wong et al. Front Pediatr 2014
Cheifetz. Respir Care 2016
• Pediatric Acute Lung Injury
Consensus Conference
(PALICC)
• Interdisciplinary group
• Pediatric-specific definition for
PARDS
• Recommendations for
management
• Research priorities
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PARDS Definition
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Khemani et al. Ped Crit Care Med 2015
Age Exclude patients with perinatal 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 infiltrates consistent with acute
pulmonary parenchymal disease
Oxygenation Non-invasive
mechanical ventilation
Invasive mechanical ventilation
Pediatric ARDS Mild Moderate Severe
Full face-mask bi-level
ventilation or CPAP ≥ 5
cm H20
PaO2/FiO2 ratio ≤ 300
SpO2/FiO2 ratio ≤ 264
4 ≤ OI < 8
5 ≤ OSI < 7.5
8 ≤ OI < 16
7.5 ≤ OSI < 12.3
OI ≥ 16
OSI ≥ 12.3
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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.
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.
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.
Khemani et al. Ped Crit Care Med 2015
How would I change my practice?
• Move away from adult-based definitions o AECC definition
o No more “acute lung injury”
o Berlin definition
• Oxygenation index and oxygen saturation index
• Increased recognition of mild PARDS
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OI = FiO2 x Mean Airway Pressure x 100 PaO2
OSI = FiO2 x Mean Airway Pressure x 100 SpO2
Overview
• Pediatric Acute Respiratory Distress Syndrome
• Current Epidemiology
• Asia’s Experience
• Concluding Remarks
10
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Crit Care Med 2016
Journal of Intensive Care Medicine 2017
Tale of Two Systematic Reviews Schouten et al.
• Aims: – Estimate population
incidence
– Estimate mortality
• Medline, Embase, CINAHL
• 1994 – August 2014
• Include both retrospective and prospective studies
• Excluded studies with < 10 patients
Wong et al.
• Aims: Describe mortality over time
• Medline, Embase and Web of Science
• 1960 – August 2015
• Included prospective studies only
• Excluded studies with < 20 patients
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29 - 32 studies 29 studies
Schouten et al. Crit Care Med 2016
Wong et al. Journal of Intensive Care 2017
Pediatric ARDS
• Population-based incidence: 3.5 per 100,000 person years (95% CI: 2.2 – 5.7)
• PICU-based incidence: 2.3% (95% CI: 1.9 – 2.9%)
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Schouten et al. Crit Care Med 2016
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Western countries
Asian countries
27% (95% CI: 22 – 34)
51% (95% CI: 42 – 63)
• Significant higher mortality in studies performed in Asia
• No change in mortality over time in Asia
Study design did not influence reported mortality rates
Schouten et al. Crit Care Med 2016
• Overall mortality: 24%
(95% CI: 19 – 31)
• A later year of study was associated with survival [OR for mortality: 0.94; 95%: 0.94 – 0.95]
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Wong et al. Journal of Intensive Care 2017
Observational studies
RCTs
• No difference in mortality reported in observational studies and RCTs
Overview
• Pediatric Acute Respiratory Distress Syndrome
• Current Epidemiology
• Asia’s Experience
• Future Directions
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PACCMAN Pediatric Acute & Critical Care Medicine Asian Network
• Pressing need for pediatric critical care medicine collaboration in Asia
• Predominantly single center studies
• Multicenter studies are often limited to single country
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Validation of PALICC’s Definition
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• Multi-center, retrospective
cohort study
• PARDS definition
according to PALICC 2015
• Study period 2009-2015
• All patients are followed up
till 100 days post diagnosis
• Included only patients on
invasive mechanical
ventilation
China
Thailand
Vietnam
Malaysia
Singapore
Patient Demographics
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Characteristic Mild PARDS
(n=89)
Moderate
PARDS (n=149)
Severe PARDS
(n=135) P value
Age, years 1.0 (0.3,4.3) 1.0 (0.3, 4.1) 2.3 (0.7, 5.5) 0.008
Gender, male 52 (58.4) 77 (51.7) 67 (49.6) 0.419
Weight, kg 8.4 (4.7, 14) 7.8 (5, 15) 11 (7, 20) 0.001
PIM 2 score 6.9 (2.8, 13.7) 7.4 (3.5, 18.3) 9.8 (4.4, 30) 0.038
PELOD score 3 (1, 12) 3 (1, 12) 11 (2, 16) 0.048
Presence of co-morbidities 36 (40.4) 77 (51.7) 84 (62.2) 0.006
Risk factors for PARDS:
Pneumonia 73 (82.0) 124 (83.2) 112 (83.0) 0.971
Sepsis 16 (18.0) 35 (23.5) 46 (34.1) 0.018
Aspiration 6 (6.7) 8 (5.4) 6 (4.4) 0.757
Transfusion 1 (1.1) 1 (0.7) 3 (2.2) 0.514
Trauma 0 (0) 1 (0.7) 2 (1.5) 0.465
Near drowning 5 (3.5) 6 (4.0) 3 (2.2) 0.414
Others 4 (4.5) 17 (11.4) 14 (10.4) 0.185
OI 5.9 (4.9, 6.7) 11.3 (9.8, 13.6) 25.2 (18.5, 33.2) < 0.001
OSI 5.52 (4.5, 7.2) 9 (7.0, 11.2) 17.1 (14.1, 22.2) < 0.001
PICU mortality: 113/373 (30.3%)
100-day mortality: 126/314 (39.7%)
100-day mortality based on
PARDS severity
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Severity Categories Unadjusted Hazard Ratio P value Adjusted Hazard Ratio P value
Mild Reference Reference
Moderate 2.69 (1.39 – 5.19) <0.01 2.64 (1.35 – 5.14) <0.01
Severe 4.15 (2.17 – 7.93) < 0.01 4.10 (2.02 – 8.32) <0.01
Using COX Proportional hazard regression model Adjusted for site, presence of co-morbidities and Pediatric Index of Mortality 2 score
Outcomes of Extrapulmonary PARDS
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PARDSp PARDSexp
Pneumonia (lower respiratory tract infections)
Sepsis (non-pulmonary)
Aspiration Trauma
Near drowning/ drowning Transfusion
Others (e.g.,pancreatitis, cardio-pulmonary bypass)
Total number of patients enrolled=438
Total number of PARDS patients fulfilling PALICC
criteria=427
Patients on NIV on day 1 of PARDS=54
Not PARDS after data
verification=11
Patients on invasive ventilation on day 1 of
PARDS=373
Patients with an identifiable main risk
factor=315
Patients with overlap risk factors=58
Pnuemonia + sepsis Pneumonia + transfusion
Pneumonia + sepsis + transfusion PARDSp=272 PARDSexp=43
Characteristics PARDSp (n=272) PARDSExp (n=43) P value
Age 1.1 (0.4, 3.6) 2.6 (0.5, 6.6) 0.0272
Gender 146 (53.7) 24 (55.8) 0.7938
Weight 8.4 (5.4, 15.0) 13.3 (6.5, 20.0) 0.0371
Co-morbidities 134 (49.3) 26 (60.5) 0.1722
Bacteremia 23 (8.5) 23 (53.5) < 0.001
PIM 2 score 6.6 (2.9, 14.1) 19.3 (6.6, 43.0) < 0.0001
PELOD score 10 (1, 12) 12 (3, 22) 0.0001
PF Ratio 126.7 (86.7, 180.0) 103.8 (65.6, 180.9) 0.0792
OI 11.3 (7.2, 17.7) 15.1 (8.6, 25.1) 0.1012
Multiorgan
dysfunction
73 (26.8) 31 (72.1) < 0.0001
Cardiovascular 54 (19.9) 26 (60.5) < 0.0001
Neurologic 21 (07.7) 3 (07.0) 0.8643
Hematologic 38 (14.0) 26 (60.5) < 0.0001
Renal 34 (12.5) 15 (34.9) 0.0002
Hepatic 35 (12.9) 19 (44.2) < 0.0001
Etiologies
PARDSp (N = 272), n (%) PARDSexp (N = 43), n (%)
Pneumonia 250 (92) Non-pulmonary sepsis 35 (81)
Aspiration 8 (3) Trauma 4 (9)
Drowning/near drowning 14 (5) Transfusion 0 (0)
Others 4 (9)
Outcomes PARDSp (n=272) PARDSExp (n=43) P value
PICU Mortality 66 (24.3) 20 (46.5) 0.002
100-day mortality 72 (32.6) 22 (53.7) 0.01
Ventilator free days 19.0 (0.5, 24.0) 2.0 (0.0, 18.0) 0.001
Ventilator Duration 8.0 (4.0, 15.0) 10.0 (4.0, 17.0) 0.295
PICU Duration 11.0 (6.0, 19.0) 12.0 (6 to 29) 0.318
PICU free days 16 (1 to 22) 10 (0 to 21) 0.069
Outcomes
26
Covariates
Unadjusted HR (95%CI) P value Adjusted HR (95%CI) P value
PIM 2 score 1.017 (1.01 - 1.024) < 0.001 1.025 (1.016 - 1.033) < 0.001
Comorbidities 1.757 (1.154 - 2.677) 0.009 2.566 (1.593 - 4.135) < 0.001
Multiorgan Dysfunction 3.278 (2.17 - 4.953) < 0.001 3.327 (1.967 - 5.628) < 0.001
PARDSExp
(Ref: PARDSp) 1.742 (1.081 - 2.809) 0.023 1.689 (0.971 - 2.935) 0.063
PARDS Severity
(Ref: Mild)
Moderate 1.801 (0.958 - 3.389) 0.068 1.498 (0.782 - 2.871) 0.223
Severe 3.478 (1.871 - 6.462) < 0.001 2.637 (1.293 - 5.381) 0.008
Cox Regression
Adjusted for site
Overview
• Pediatric Acute Respiratory Distress Syndrome
• Current Epidemiology
• Asia’s Experience
• Concluding Remarks
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Concluding Remarks
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• Increasing studies in PARDS over the next 5 – 10 years
• PALICC consensus statements’ publication is a major step in pediatric critical care
• Future studies should consider the needs and gaps highlighted by this document
• Long term follow-up of survivors of PARDS
• Multi-center studies across the globe to compare and contrast current practices
Concluding Remarks
30
• Demonstrated that multi-center collaboration is
feasible
• Barriers will be present but these can be
overcome
• Establishing collaboration between continents is
equally important
MALAYSIA
THAILAND
VIETNAM SINGAPORE
CHINA
