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