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PAEDIATRIC RESPIRATORY FAILURE
Tang Swee Fong
Department of Paediatrics
University Kebangsaan Malaysia Medical Centre
Outline of lecture
Bronchiolitis
Bronchopulmonary
dysplasia
ARDS
Asthma
Bronchiolitis
Bronchiolitis - Epidemiology
Deaths (100)
Hospitalisations (57,000-172,00 – 2-3% of children
<12 months)
Outpatient care (800,00 children -
20% of birth cohort)
• Hospital charges:
– >$1.7 billion in 2009
• 66,000 to 199,000 deaths
in children <5 years of
age (mainly in resource-
limited countries)
Hall CB, et al. New Engl J Med 2009;360:588-98
Nair H, et al. Lancet 2010;375:1545-55
Bronchiolitis - Management
• Lack of curative therapy
Wheeze
Bronchodilators
Corticosteroids
“Clinicians should not administer albuterol (or salbutamol)
to infants and children with diagnosis of bronchiolitis”
AAP Guidelines 2014
Hypertonic saline
Draw fluid from submucosal and adventitial spaces
replenishes air liquid surface and improve clearance of airway
• Double-blind RCT – 3%HS vs 0.9%NS
• 68 patients (HS: 33; NS:35)
• Mild to moderate acute viral bronchiolitis
Major outcomes
Hypertonic saline
Group 1 (HS)
N=33
Normal saline
Group II (NS)
N=35
p value
Days until ‘fit to discharge’
(mean + SD) 4.9 + 2.4 4.7 + 2.3 0.621
Days until discharge
(mean + SD) 5.6 + 2.3 5.4 + 2.1 0.747
Severity score D1 (33, 35)1 5.8 + 2.1 6.3 + 1.7 0.286
Severity score D2 (33, 34)1 5.9 + 2.3 6.8 + 2.4 0.099
Severity score D3 (29, 31)1 5.5 + 3.2 5.6 + 2.7 0.865
Severity score when „fit to
discharge‟ (33, 35)1 1.3 + 1.4 1.5 + 1.3 0.575
Flores P, et al. Pediatr Pulmonology 2016;51:418-25
1 (N Group I, N Group II)
Major outcomes
Hypertonic saline
Group 1 (HS)
N=33
Normal saline
Group II (NS)
N=35
p value
Days until „fit to discharge‟
(mean + SD) 4.9 + 2.4 4.7 + 2.3 0.621
Days until discharge
(mean + SD) 5.6 + 2.3 5.4 + 2.1 0.747
Severity score D1 (33, 35)1 5.8 + 2.1 6.3 + 1.7 0.286
Severity score D2 (33, 34)1 5.9 + 2.3 6.8 + 2.4 0.099
Severity score D3 (29, 31)1 5.5 + 3.2 5.6 + 2.7 0.865
Severity score when ‘fit to
discharge’ (33, 35)1 1.3 + 1.4 1.5 + 1.3 0.575
Flores P, et al. Pediatr Pulmonology 2016;51:418-25
1 (N Group I, N Group II)
Minor outcomes
Hypertonic saline
Group 1 (HS)
N=33
Normal saline
Group II (NS)
N=35
p value
Supplemental oxygen, duration (h) 91 + 39 86 + 40 0.640
Further doses of salbutamol 17 (51.5) 23 (65.7) 0.234
Nebulised epinephrine 9 (27.3) 23 (14.3) 0.186
Systemic corticosteroids 8 (24.2) 10 (28.6) 0.686
Antibiotics 18 (54.5) 13 (37.1) 0.150
Flores P, et al. Pediatr Pulmonology 2016;51:418-25
Patients in HS group had significantly more
• Cough (46% vs 20%, p=0.025)
• Rhinorrhoea (58% vs 31%, p=0.03)
„Our results do not support the use of HS in
infants with bronchiolitis‟
Thorax 2014;69:1105-1112
• 10 hospitals in UK
• 317 infants (HS: 158; NS: 159)
• 3% HS vs standard therapy
SABRE
(hypertonic Saline in Acute Bronchiolitis Rct and
Economic evaluation
Hazard ratio: 0.95,
(95%CI: 0.75-1.20)
Hazard ratio: 0.97,
(95%CI: 0.76-1.23)
Everard M, et al. Thorax 2014;69:1105-1112
“This study does not support the use of nebulised
HS in the treatment of acute bronchiolitis over
usual care with minimal handlings”
Pediatr Crit Care Med 2017;18:e106-e111
• Retrospective, cohort study
• Single centre
• 135 patients
Early fluid overload prolongs
mechanical ventilation
0
100
200
300
1 2 3 4 5 6
Cu
mu
lati
ve f
luid
bala
nce (
mL
/kg
)
Study day
• 92.6% had a positive
cumulative fluid balance
starting on day of admission
• Duration of mechanical
ventilation positively
correlated with mean
cumulative fluid balance
• No association between
fluid status and OSI
*
**
* *
*p<0.05
*p<0.01
Ingelse SA, et al. Pediatr Crit Care Med 2017;18:e108-e111
(Pediatr Crit Care Med 2017;18:e106-e111)
“Early fluid overload independent predictor of prolonged
mechanical ventilation”
Crit Care Med 2012;40:2883-9
New Engl J Med 2006;354:2564-75
(Crit Care Res Pract 2011;854142)
p<0.02, 95%CI 1.09 (1.00, 1.18)
p<0.02, 95%CI -0.21 (-0.42, -0.01)
Judicious fluid
management
• Aim
• HFWHO provided enhanced respiratory support
Shorter time to weaning off oxygen
• Treatment arm
• HFWHO (1L/kg to maximum of 20 L, maximum
FiO2 of 0.6)
• Control arm
• standard therapy (cold wall oxygen 100% via nasal
cannulae at low flow to a maximum of 2L/min)
Lancet 2017;369:930-9
HFWHO – treatment failure and
care escalation (ITT)
Standard
therapy
N (%)
HFWHO
N (%)
p value Difference
(95%CI)
Treatment
failure
33 (33) 14 (14) 0.0016 19% (8-30)
Crossover
32 (32) 1 (1) <0.0001 31% (17-44)
Rescued
20 (20) - - -
ICU transfer 17 (12) 14 (14) 0.41 -1%
(-7 to 16)
Kepreotes E, et al. Lancet 2017;369:930-9
HFWHO - summary
• HFWHO
• and standard therapy were both effective
• early use did not alter overall course of bronchiolitis
• prevented deterioration in significantly more infants
• able to reverse deterioration in 63%
Kepreotes E, et al. Lancet 2017;369:930-9
“This study provides evidence for the use of HFWHO at a
maximum of 1L/kg per min (FIO2 0.6) in the management of
children with bronchiolitis of moderate severity for whom
standard therapy with oxygen at 2L/min has failed or have used
HFWHO from the outset”
Supplemental
oxygen
Minimal handling Provision and
judicious use of
fluids
Bronchiolitis management in 2017
Chronic lung disease of infancy
(Bronchopulmonary dysplasia)
• BPD complicated with pulmonary hypertension
associated with increased morbidity and
mortality
• 18 patients with BPD
• Pulmonary pressure assessment:
• Echocardiography and cardiac catheterisation
• PH medication:
• Sildenafil alone - 12,
• Sildenafil + Bosentan – 5,
• Bosentan alone – 1
• Clinical improvement
• A decrease in Ross functional class by at least one
degree
• Haemodynamic improvement
• A decrease in pulmonary hypertension severity by one
level
Ross functional class over time Echocardiographic score over time
3.2 + 0.9 vs 1.7 + 0.9, p<0.0001 Moderate or severe PH 72%
vs 17% moderate PH, p<0.001
„PAH-targeted therapy can be useful for infants with
BPD and PH on optimal treatment of underlying
respiratory and cardiac disease
(Class IIa; Level ofEvidence C)‟
Circulation 2015;132
Asthma
Magnesium sulphate infusion
Pediatr Crit Care Med 2016;17:e29-33
• Prospective randomised open-label trial
• 6-16 year old with severe asthma
• Emergency department
• iv MgSO4 50mg/kg bolus vs high dose infusion
50mg/kg/hr for 4 hours
Outcomes
Main outcomes Bolus High dose
infusion
p value
LOS < 24 hrs, n (%)
2 (10.5) 9 (47.4) 0.032
Absolute risk
reduction 37%;
95% CI, 10-63;
NNT, 3
LOS (hr) (mean + SD)
48 + 19
34 + 19 0.013
Cost (US$) (mean + SD) 834.37 + 306.73
603.16 + 338.47
0.016
Irazuzta et al. Pediatr Crit Care Med 2016;17:e29-33
Outcomes
Main outcomes Bolus High dose
infusion
p value
LOS < 24 hrs, n (%)
2 (10.5) 9 (47.4) 0.032
Absolute risk
reduction 37%;
95% CI, 10-63;
NNT, 3
LOS (hr) (mean + SD)
48 + 19
34 + 19 0.013
Cost (US$) (mean + SD) 834.37 + 306.73
603.16 + 338.47
0.016
Irazuzta et al. Pediatr Crit Care Med 2016;17:e29-33
“Early utilisation of high-dose prolonged
MgSO4 infusion …expedites discharge from
emergency department with significant
reduction in healthcare cost”
“..if a little is good, more is even better?”
• Comparatively easy to use
• Relatively good side effect profile
• Inexpensive
• ? Higher dose short term infusion
useful adjunct
Acute Respiratory Distress
Syndrome
Pediatr Crit Care Med 2016;17:101-9
Alveolar dead space fraction = (PaCo2 – PetCO2) / PaCO2
AVDSf
AVDSf
AUROC 0.76;
(95% CI, 0.66-0.85;
p<0.001)
Yehya N, et al. Pediatr Crit Care Med 2016;17:101-9
Better than OI
or PaO2/FiO2
Pediatr Crit Care Med 2017;18:e229-e234
Oxygenation
Pediatr Crit Care Med 2017;18:e229-e234
• 12 mechanically ventilated patients
• Responders: >10% increase in OI
Changes in oxygenation and
regional ventilation Responders (n=4) Non-responders (n=8)
Baseline 60 min Baseline 60 min
OI 10 + 8 5 + 2 9 + 7 11 + 10
% change in OI N/A -39 + 21 N/A 23 + 43
PaO2/FiO2 170 + 92 247 + 80 173 + 59 156 + 44
SpO2/FiO2 200 + 80 240 + 73 214 + 72 225 + 65
• Responders
• proportion of ventilation increased in dorsal lung (49% to 57%)
• Improvement in ventilation homogeneity
Lupton-Smith A, et al.. Pediatr Crit Care Med 2017;18:e229-e234
Novel insights on ventilation distribution on
turning prone
• Not all infants and children respond positively
• Degree of response variable
• Ventilation becomes more homogenous with
time improving V/Q matching
• Highlights clinical utility of electrical impedance
tomography to aid in identifying those more
likely to respond
JPEN J Parentr Enteral Nutr 2016
• ? Nutrition delivery to children pARDS
• ? Provision of adequate nutrition improved clinical outcomes
Caloric intake Protein intake
ICU mortality with adequate caloric intake,
34.6% vs 60.5%, p=.025
ICU mortality with adequate protein intake,
14.3% vs 60.2%, p=.002
Significantly associated with
ventilator-free days
JPEN J Parentr Enteral Nutr 2016
• Adequate nutrition delivery improves clinical outcome
• Protein delivery may have potentially more impact than
caloric intake
Pediatri Crit Care Med 2017;18:675-715
Guidelines for provision and assessment of
nutrition support therapy
• Reiterates importance of nutritional assessment
• Need for renewed focus on
• Accurate estimation of energy needs
• Attention to optimising protein intake
• Optimal route and timing of nutrient delivery still
debated and investigated – enteral nutrition
preferred route of delivery
JAMA 2016;316:1583-9
PaO2 (mmHg)
SpO2 (%)
Conservative
70-100 94-98
Conventional
Up to 150 97-100
• Open-labelled RCT
• Expected length of stay > 72 hours
Unplanned early termination
JAMA, 2016;316:1583--9
Oxygen-ICU: ICU mortality
Girardis M, et al. JAMA 2015;316:1583-9
Conventional
• PaO2 up to 150 mmHg
• SpO2 97%-100%
Conservative
• PaO2 70 to 100 mmHg
• SpO2 94%-98%
JAMA 2016;316:1583-9 Oxygen therapy, No. (%) Absolute risk
reduction
(95%CI)
p value
Conservative
(n=216)
Conventional
(n=218)
Primary outcome
• Mortality
25 (11.6)
44 (20.2)
0.086
(0.017-0.150)
NNT 12
0.01
Secondary
outcome
• Shock
• Liver failure
• Bacteraemia
8 (3.7)
4 (1.9)
11 (5.1)
23 (10.6)
14 (6.4)
22 (10.1)
0.068 (0.020-
0.120)
0.046 (0.008-0.088)
0.050 (0.000-
0.090)
0.006
0.02
0.049
Potential impact to current practice
• Mindful of the potential harms of hyperoxia in
critically ill patients
• Judicious use of supplemental oxygen – titrating
to maintain normoxia
Am J Respir Crit Care Med 2017;195:331-8
Clinical outcome by ARDS Subphenotype
Subphenotype 1
(n=727)
Subphenotype 2
(n=273)
p value
60-d mortality, % 21 44 <0.0001
90-d mortality, % 22 45 <0.001
Ventilator-free days,
median
19 3 <0.001
Clinical outcome by ARDS Subphenotype
Subphenotype 1
(n=727)
Subphenotype 2
(n=273)
p value
60-d mortality, % 21 44 <0.0001
90-d mortality, % 22 45 <0.001
Ventilator-free days,
median
19 3 <0.001
Interaction between ARDS Subphenotype and
Fluid Management Strategy
Fluid
management
strategy
Subphenotype 1 Subphenotype 2 p value
Conservative
(n=349)
Liberal (n=367) Conservative
(n=142)
Liberal
(n=131)
60-d mortality, % 24 17 39 49 0.0093
90-d mortality, % 26 18 40 50 0.0039
Ventilator-free days,
median
17 21 5 0 0.35
Lancet Respir Med 2014
Association between phenotype assignment and
clinical outcome
ARMA cohort ALVEOLI cohort
Phenotype 1
(n=308)
Phenotype 2
(n=155)
p value Phenotype 1
(n=404)
Phenotype 2
(n=145)
p value
90-d mortality 23% 44% 0.006 19% 51% <0.001
Ventilator-free
days
17.8 7.7 <0.001 18.4 8.3 <0.001
Organ-failure
free days
14.5 8.0 <0.001 16.5 8.4 <0.001
Phenotype 1 (n=404) Phenotype 2 (n=145)
Low PEEP
(n=202)
High PEEP
(n=202)
Low PEEP
(n=71)
High PEEP
(n=74)
p value
90-d mortality 33 (16%) 48 (24%) 36 (51%) 31 (42%) 0.049
Ventilator-free days 20 (10-25) 21 (3-24) 2 (0-21) 4.5 (0-20) 0.018
Organ-failure free days 22 (11-26) 22 (9-26) 4 (0-18) 6.5 (0-21) 0.003
Differences in response to PEEP strategy
(ALVEOLI cohort only)
Amer J Respir Crit Care Med 2017;195:3:280-1
PAEDIATRIC RESPIRATORY FAILURE
2026/2027
Thank you