Respiratory support for infants with bronchiolitis, a narrative review of the literature

Accepted Manuscript Clinical usefulness Respiratory Support for Infants with Bronchiolitis, a Narrative Review of the Literature Donna Franklin, John F. Fraser, Andreas Schibler PII: DOI: Reference:

S1526-0542(18)30116-7 https://doi.org/10.1016/j.prrv.2018.10.001 YPRRV 1290

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Paediatric Respiratory Reviews

Please cite this article as: D. Franklin, J.F. Fraser, A. Schibler, Respiratory Support for Infants with Bronchiolitis, a Narrative Review of the Literature, Paediatric Respiratory Reviews (2018), doi: https://doi.org/10.1016/j.prrv. 2018.10.001

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Respiratory Support for Bronchiolitis

Respiratory Support for Infants with Bronchiolitis, a Narrative Review of the Literature

1,2,3,4

Donna Franklin, PhD Candidate BN MBA John F Fraser MBChB PhD FRCP (Glas) FRCA FFARCSI FCICM 1,2,3 Andreas Schibler, MD FCICM 3,4

1

Paediatric Critical Care Research Group, Lady Cilento Children's Hospital Mater Research Institute, The University of Queensland, Brisbane, Australia 3 The University of Queensland, School of Medicine, Brisbane, Australia 4 Critical Care Research Group, Adult Intensive Care Service, The Prince Charles Hospital, Brisbane, Australia. 2

Address for contact: Donna Franklin Paediatric Intensive Care Unit Paediatric Critical Care Research Group (PCCRG) Centre for Children’s Health Research, Lady Cilento Children's Hospital Precinct and Mater Research Institute, The University of Queensland
 Level 7, 62 Graham St, South Brisbane, Queensland, 4101, Australia
 [email protected]

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Summary

1

Respiratory Support for Bronchiolitis

2

Bronchiolitis is a common viral disease that significantly affects infants less than 12 months of age. The purpose of this review is to present a review of the current knowledge of the uses of respiratory support in the management of infants with bronchiolitis presenting to hospital. We electronically searched MEDLINE, Cochrane, CINAHL and EMBASE (inception to 25th March 2018), to manually search for clinical trials that address the management strategies for respiratory support of infants with bronchiolitis. We identified 120 papers who met the inclusion criteria, of which 33 papers were relevant for this review with only nine randomised controlled trials. This review demonstrated that noninvasive respiratory support reduced the need for escalation of therapy, particularly the proportion of intubations required for infants with bronchiolitis. Additionally, clear economic benefits have been demonstrated when non-invasive ventilation has been used. The potential early use of non-invasive respiratory supports such as nasal high flow therapy and non-invasive ventilation may have an impact on health care costs and reduction in ICU admissions and intubation rates. High-grade evidence demonstrates safety and quality of high flow therapy in general ward settings.

Word Count - 185

Educational aims:

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The reader will come to appreciate: 

The management of infants with bronchiolitis who require respiratory therapies has evolved over the last two decades moving towards less invasive modalities.



The impact of non-invasive respiratory therapies has shown a likely reduction on hospital length of stay and intensive care admission.



Nasal high flow therapy is now the preferred respiratory support in the form of noninvasive ventilation as it can be safely applied in non-intensive care environments.



The use of high flow therapy is a promising intervention but needs further definition of when and how to be used.

Future research directions:

Evidence from high quality randomised controlled trials has demonstrated that non-invasive respiratory therapies for infants with bronchiolitis in Intensive Care Unit’s (ICU) is effective treatment. Future research on the use of these therapies outside of intensive care units would be greatly beneficial. The key remaining issues are: 

Where and when (how early) should respiratory support be initiated?



Identifying risk factors that support the use of nasal high flow or non-invasive ventilation to avoid invasive ventilation in bronchiolitis.



What are the optimal respiratory support methods delivering better outcomes such as length of stay, reduced proportion of escalation of therapy (i.e. need for intubation) or even mortality?



Importantly, in which clinical settings (general paediatric ward or intensive care/high dependency care) should these respiratory systems be used?

Respiratory Support for Bronchiolitis Keywords Bronchiolitis, Respiratory Syncytial Virus (RSV), Infant, Nasal High Flow, Non-Invasive Ventilation, Invasive Mechanical Ventilation, Standard Oxygen Therapy

4

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INTRODUCTION

Viral bronchiolitis is the most common respiratory disease in infants and young children less than 24 months of age, leading to a large number of hospital and intensive care admissions with an ever-increasing health care burden (1-3). The current treatment modalities of bronchiolitis either attempt to reduce hospital admission reduce the length of stay, or for the more severe disease, avoid admission to intensive care and prevent intubation and mechanical ventilation. Previously, pharmaceutical therapies have had little impact on these outcomes (4, 5). In recent studies, a greater focus has been on optimizing respiratory support of infants with bronchiolitis, particularly to prevent intubation and mechanical ventilation.

Currently, there is a wide array of modalities offered to infants with more severe bronchiolitis including standard oxygen therapy, nasal high flow (NHF) therapy, non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) and invasive mechanical ventilation (IMV). Depending on the course of the illness, this cohort may require a number of these respiratory support modes during one hospital admission. Larger retrospective studies have demonstrated a reduction in the use of invasive mechanical ventilation with an associated intrinsically reduced complication and morbidity rate (6). A recent epidemiological study from the United Kingdom with observations over a period of 30 years (1985-2015) showed an increasing hospital admission rate of infants with bronchiolitis and naturally increased frequency of the use of respiratory support (1).

Most of the respiratory support modes for bronchiolitis have been introduced without highgrade evidence and were based more on observation of improved physiology and cohort studies rather than prospective studies (7-9). The most pertinent questions for clinicians

Respiratory Support for Bronchiolitis remain: Are there factors predicting the need for respiratory support such as NHF therapy, CPAP or invasive ventilation, which is best and where and when should these therapies be introduced?

6

Respiratory Support for Bronchiolitis

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Definitions of respiratory supports for infants with bronchiolitis. Standard oxygen therapy (SOT) for the purpose of this review was defined as subnasal oxygen with 100% oxygen up to 4L/min, facemask oxygen delivery up to 8L/min dependent on age or oxygen delivery using a head box. Most of the studies using SOT did not specify whether the oxygen delivery was humidified or not. Nasal High Flow (NHF) therapy. Accurate oxygen delivery and an estimate of the required inspired oxygen fraction (FiO2) can be achieved by delivering a high inspiratory flow rate through nasal cannula using heated, humidified and blended gas as a mixture of oxygen and air. The ideal flow rates should match the inspiratory demand of the patient to avoid entrainment of air (10). The delivery of NHF therapy has several proven physiological benefits, which include: CO2 washout of the anatomical dead space of the upper airway; humidification and heating of the inspired gas; reduced inspiratory work of breathing and creation of positive expiratory airway pressure (11). As there is currently no consensus on the precise definition of NHF therapy, we accepted the definition of the authors of each individual study as a valid definition of NHF therapy. However, we evaluated the studies carefully whilst considering the flow rates delivered. The most commonly described and accepted definition of NHF therapy rates for infants with bronchiolitis was 1-2 L/kg/min. Non-invasive ventilation (NIV). Continuous positive airway pressure (CPAP) or non-invasive ventilation using biphasic positive airway pressure [BiPAP] uses a dedicated ventilator and patient ventilator interfaces such as a face masks, nasal masks or helmets for CPAP/NIV. CPAP provides a similar airway pressure during the inspiratory and expiratory phases whereas biphasic NIV uses either triggered or non-triggered two levels of positive airway pressure, hence greater pressures during the inspiratory phase. CPAP is commonly used with a CPAP driver but can

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also be used with a bubble CPAP device. The assumption that the CPAP pressure chosen is the CPAP pressure delivered and applied has been shown to be inaccurate with most studies showing the effective airway pressures being lower (12).

Invasive mechanical ventilation (IMV) This was defined as providing conventional positive pressure ventilation or high frequency oscillatory ventilation (HFOV) via an endotracheal tube and a dedicated ventilator/oscillator. Each of these respiratory modalities was additionally evaluated considering the settings in which the support was provided: emergency department (ED), paediatric ward (PW), high dependency unit (HDU) and intensive care unit (ICU).

Study population. Infants aged less than 24 months with bronchiolitis admitted to hospital requiring respiratory support or oxygen therapy were included. Definition of bronchiolitis is as a viral illness characterized by coryzal symptoms for the first 1-3 days, which worsens on days 3-5 with increased work of breathing and auscultatory findings of possible crackles and wheeze.

Search strategy and study selection. We electronically searched MEDLINE, Cochrane, CINAHL and EMBASE (inception to 25th March 2018), to manually search for clinical trials that addressed the management strategies for respiratory support of infants with bronchiolitis. The following key words were searched for: bronchiolitis, bronchiolitic, respiratory syncytial virus, humans, respiratory syncytial virus infections, RSV, infant, baby, babies, neonate, new-born, paediatric, pediatric, child, 12 months, respiratory therapy, respiration artificial, respiratory support, continuous positive airway pressure, CPAP, positive-pressure respiration, HFNC, HHFNC, HHHFNC, high flow

Respiratory Support for Bronchiolitis

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nasal cannula therapy, high flow therapy, oxygen inhalation therapy, head box, oxygen tent, mask, hood, heliox, oxygen treatment, oxygen therapy, non-pharmaceutical, mechanical, room-air, oxygen delivery devices.

Excluded were papers with less than 10 cases discussed, papers describing the epidemiology of bronchiolitis, pharmaceutical interventions or physiotherapy. For the purpose of a more meaningful discussion we are only discussing high-grade papers with relevance to the clinical outcome, as there were many case series that were less relevant for the purpose of this literature review. Only fully reported studies were included in the reporting.

Data extraction and synthesis. All exports from the search databases were screened by both authors independently and assessed for eligibility for the purpose of this review. Grading of each paper with the level of evidence was also completed independently by each author (Table 1).

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Respiratory Support for Bronchiolitis RESULTS Inclusion criteria included:  Bronchiolitis  Mist therapy  Oxygen supplementation  Nebulised Saline  Heliox  Oxygen therapy  HFNC/HHFNC/HHHFNC  CPAP  Intubation & Ventilation  <12 months & <24 months

Records identified through database searches: Medline Ebsco (760) CINAHL (195) Central Register of Controlled Trials Cochrane (136) Embase (1674) TOTAL n = 2765

Exclusion criteria included:  Pharmaceutical related therapy  Non-English  Physiotherapy related  Epidemiology studies describing bronchiolitis  Abstracts  Paper with <10 patients in study  Duplicates (442)

Reduced down to reviewing 120 papers

33 studies discussed in the literature review

Figure 1. Literature search strategy

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Comparison of respiratory support modes (Table 2) A total of 9 relevant trials were identified comparing two or three respiratory support modes with a true randomisation. A recent well conducted RCT comparing the use of NHF therapy and CPAP in a French multi-centre PICU study showed that NHF therapy is not inferior but had a proportionally greater failure rate (need to change respiratory support method) than CPAP (13). Infants in both intervention groups had a similar intubation rate. In a small multicenter PICU study helmet CPAP was successfully compared with facemask CPAP in infants with RSV bronchiolitis. The authors have shown a higher tolerance of helmet CPAP, but there was no difference in intubation rates (14). A recent single-centre RCT comparing standard SOT with NHF therapy showed no difference in the length of oxygen therapy (primary outcome) but showed a significantly reduced failure rate (defined as intensive care admission) in the NHF therapy group (15). The recent multi-center PARIS trial performed in Australia and New Zealand, is currently the largest RCT comparing NHF therapy with SOT in paediatric ward settings in general hospitals or tertiary children’s hospitals. The results showed a reduced failure rate of NHF therapy (12%) compared to SOT (23%), but no difference in the overall length of stay in hospital (16). The trial showed a high safety and quality profile in infants with bronchiolitis aged less than 12 months.

A recent study in limited resource settings compared SOT, NHF therapy and bubble CPAP (17). This study enrolled children up to five years of age with acute respiratory failure, of which approximately 10-15 % had bronchiolitis. The trial was prematurely terminated after an interim analysis. The data demonstrated that the use of bubble CPAP reduces the mortality in comparison to SOT but no difference between NHF therapy and bubble CPAP could be found.

Respiratory Support for Bronchiolitis

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Thia et al. compared in a cross-over RCT, SOT to nasal CPAP in a small randomised controlled cross over study and showed significantly improved CO2 clearance using nasal CPAP (18).

A blinded RCT comparing SOT with Heliox showed reduced work of breathing after 8 hours of delivery but no impact on length of stay or oxygen treatment required (19). In subgroup of infants with severe bronchiolitis requiring additional CPAP support, those receiving Heliox on CPAP had a significant reduced length of treatment. Clement et al. could show that improved ventilator patient synchrony can be achieved with Neurally adjusted ventilator assist (NAVA) compared to standard pressure trigger ventilation, which was also confirmed in a non-randomised smaller trial by Baudin et al. (20, 21). No trials could be identified comparing outcomes directly between NHF/CPAP/NIV and IMV.

Cohort studies comparing or describing practice in intensive care (Table 3) A total of 10 trials were identified describing cohorts and practice using respiratory support in intensive care. Pierce et al. described in a prospective survey of 16 children’s hospitals the institutional differences in practice of infants with bronchiolitis requiring ICU admission (22). Clinicians in these ICUs used CPAP in 15% of infants as a first line treatment, NHF therapy in 24% and in 26% intubation and mechanical ventilation. These differences were not site specific nor disease severity related, indicating high variability in institutional approaches to offering respiratory support.

The few identified studies showed improved outcomes if CPAP/NIV is used as the first line treatment compared to IMV. Javouhey et al demonstrated, in a well matched historical control study, that during a period when IMV was used as the primary mode of respiratory

Respiratory Support for Bronchiolitis

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support compared to a subsequent period during which NIV was used, that infants receiving primarily IMV had a higher rate of secondary bacterial infections and a greater proportion of patients with oxygen dependency after 8 days (23). Another study by Borckink et al, examined the outcome of two hospitals with different respiratory management approaches (24). One hospital used NIV as the primary support whereas the other used IMV. The use of NIV was superior in regard to length of respiratory support, however there were differences noted in the severity of the disease during the inclusion phase. Reduced length of stay in PICU and the associated reduced health care costs after introduction of NIV was described in a large French retrospective cohort study (25). An observational study showed that with increasing use of NIV the proportion of intubations dropped in infants with bronchiolitis (26). Similarly, observational studies showed that after the introduction of NHF as the standard approach for oxygen therapy in intensive care that the intubation rates decreased to less than 10% from originally greater than 30% (9, 27, 28). In the younger age group of < 28 days, Bermudez showed that with the introduction of NHF therapy intubation rates could be reduced (29). A large retrospective study describes a high safety standard for the use of NHF during transport of infants with bronchiolitis (30). Two recent reports described the variability of intensive care practice in infants with bronchiolitis (31, 32). The larger Australian and New Zealand registry study showed high variability in practice with some hospitals preferentially invasively ventilating infants with bronchiolitis, a practice that remained variable after risk adjustment.

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Cohort studies comparing or describing practice in general wards and emergency departments (Table 4) In a prospective study, 61 infants with bronchiolitis were allocated to NHF and compared during the same period to infants treated with SOT (33). Both groups showed a similar disease severity but infants on SOT had a significantly greater proportion of ICU admissions. The introduction of NHF therapy in an emergency department showed a significant reduction in the odds of intubation in ED suggesting the early use of NHF therapy may prevent escalation of therapy (34). A similar finding was found in an Italian study in general ward settings (35). Riese et al. showed a clinical benefit in addition to reduced health care costs once NHF therapy in the general paediatric ward was introduced with a strict protocol (36).

Physiological studies. A total of 7 trials were identified describing important physiological findings. There were several physiological studies either using a cross over or a randomised controlled trial design (8, 37-41). All of these physiological studies, with some being reported as early as the 1990’s, demonstrated significant improvement in either respiratory mechanics, work of breathing or gas exchange with improved CO2 clearance or oxygenation. Others showed success with a CPAP helmet methods approach despite relatively small numbers of infants investigated (42). The combination of CPAP or NHF with heliox may have a greater improvement of respiratory mechanics than CPAP alone (43, 44).

Studies predicting the need for respiratory support. One trial identified the best predictors for requiring respiratory support, which included a higher heart rate and higher respiratory rate, young age including gestational age and a

Respiratory Support for Bronchiolitis

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baseline oxygen requirement (45). Another trial showed that high FiO2 requirements, history of intubation, and cardiac co-morbidity are associated predictors of NHF failure (46). Economic benefits and reduced intubation. Essouri et al. showed that the use of nCPAP reduced the proportion of intubation and invasive mechanical ventilation in a historical cohort associated with economic benefits (25).

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DISCUSSION

The review of the existing literature for respiratory support modalities in infants with bronchiolitis showed that there is increasing high-grade evidence to recommend the use of non-invasive respiratory support in the form of NHF therapy or CPAP to prevent invasive mechanical ventilation. There is also high-grade evidence that NHF therapy can be safely used in general wards and that NHF reduces the requirement to escalate therapy.

Studies reporting on respiratory support in infants with bronchiolitis need to be carefully considered in relation to the historically improved care of these infants over time and the pragmatic approach by clinicians to reduce the use of invasive ventilation. Admission to ICU is not a completely objective measure and often determined by a number of variables other than just the physiological status of the patient, particularly for a low mortality condition like bronchiolitis. All studies uniformly suggest that on the more severe end of the disease spectrum, any form of non-invasive respiratory support (NHF therapy or CPAP) has the potential to reduce the intubation rate. The question remaining however is: where and when (how early) should respiratory support be initiated? Traditionally respiratory support for infants with bronchiolitis in the form of CPAP and NIV has been the domain of intensive care. With the introduction of NHF therapy however, the option to start early respiratory support as early as when an infant presents to the emergency department or when transferred to a general paediatric ward, has widened the scope of non-invasive ventilation for infants with bronchiolitis.

Two recent randomised controlled trials showed a reduced failure rate if NHF therapy is started immediately after hospital admission compared to SOT (15, 16). Both trials offered

Respiratory Support for Bronchiolitis

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rescue NHF therapy after treatment failure in the SOT arm of the study and the use of rescue NHF was successful in both studies. The results of both of these trials therefore are nonconclusive in regard to answer the question if early or late (rescue) NHF therapy is superior. Both studies showed no difference in length of oxygen therapy or length of hospital stay. The key messages of both trials are: NHF therapy can be safely used in general wards and can be used in hospitals without direct access to a paediatric intensive care. In both studies, NHF therapy was comparable to SOT without any change in staffing or patient flow. NHF therapy can be recommended in general paediatric wards normally caring for infants with bronchiolitis and with an oxygen requirement. The optimal threshold for oxygen therapy in infants with bronchiolitis remains a topic of debate. The UK SIGN guidelines recommended oxygen therapy in bronchiolitis to achieve oxygen saturations of  94% whereas the American Academy of Pediatrics recommends a more conservative approach with saturation of  90% (47, 48). Oxygen saturation targets in infants with bronchiolitis were investigated previously in a double blinded study, which showed no clinically relevant differences between an oxygen saturation threshold of  94% or  90% (49, 50). In the recent PARIS trial, the average inclusion saturation at the start of the intervention was 88% in room air (16).

Reviewing the literature for respiratory support in bronchiolitis in intensive care, CPAP showed slightly superior results compared to NHF therapy with a higher success rate but no differences in the intubation rate (13). Very few infants have been studied on facemask or helmet CPAP (14). The helmet CPAP seems to have a high tolerance level. Despite the lack of RCTs comparing invasive ventilation as the primary modality of respiratory support versus NIV/CPAP, several convincing historical case control studies indicate that CPAP/NIV should be used as the first line therapy over invasive ventilation.

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Invasive ventilation was associated with a greater rate of secondary infections and prolonged stay in PICU (51). Despite not being directly reported in these studies, it is likely that these invasively ventilated infants received a greater amount of sedatives, which is well known to be associated with potential impact on neurodevelopment (52). Considerable variability in practice between units is observed, with six-fold differences in risk-adjusted intubation rates that were not explained by ICU type, size, or major patient factors (32).

A randomised controlled trial, comparing SOT versus NIV or NHF therapy without offering any form of NIV/NHF therapy before IMV is likely ethically unacceptable these days but would contribute to the scientific knowledge such as a recent adult RCT, in which SOT, NIV and NHF therapy were directly compared for intubation rates (53). Interestingly this trial did not show any difference between NHF therapy and NIV, but the 90-day mortality rate in the NHF therapy group was significantly lower.

The findings of this review suggest that there is increasing data which indicates that commencing respiratory support with NHF therapy in the emergency department or general paediatric wards is of reasonable clinical benefit. The exact timing of the start of the NHF therapy in these wards is still unclear as to whether early or late (rescue) therapy should be recommended. If an infant with bronchiolitis then further deteriorates requiring HDU or ICU, then CPAP is likely the rescue option for some of these infants and may prevent intubation.

Conclusion. Bronchiolitis remains one of the most common reasons for non-elective hospital admission with a high rate of ICU admission but with a very low mortality rate overall. The use of NIV or NHF therapy historically has reduced the intubation rates. The future trend is to offer

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respiratory support such as NHF therapy outside high dependency or intensive care, reducing health care costs and potentially further reduced the need for invasive ventilation. There will always remain a selective high-risk subgroup of infants with bronchiolitis who are more likely to not benefit from NIV or NHF therapy.

Respiratory Support for Bronchiolitis Table 1: Grading of studies.

LOE 1

RCTs (or meta-analysis of RCTs)

LOE 2

Studies using concurrent controls without true randomisation

LOE 3

Studies using retrospective controls

LOE 4

Studies without a control group

LOE 5

Studies not directly related to the specific patient/population

LOE: Level of evidence

20

21

Respiratory Support for Bronchiolitis Table 2. Comparison of respiratory support methods.

Study

Key results

LOE

NHF therapy and Higher success rate

High failure rate

1

nasal CPAP in

using nCPAP but no

of NHF therapy

PICU

difference in

but no difference

airway pressure (nCPAP)

secondary outcome

in patient centred

for the initial respiratory

such as intubation rate,

outcomes such as

management of acute

duration of NIV or

intubation rates.

viral bronchiolitis in

invasive mechanical

NHF therapy

young infants: a

ventilation

was better

High flow nasal cannula (HFNC) versus nasal continuous positive

multicenter randomized controlled trial. (Milesi et al. 2017) (13)

n

142

Disease and age

Bronchiolitis < 6 months

Study type

Devices and

and design

settings

RCT

Outcomes

tolerated.

22

Respiratory Support for Bronchiolitis Continuous Positive

30

CPAP delivered

The number of days on The treatment

by helmet or

CPAP was similar in

failure rate was

Helmet Versus Mask in

facial mask in

both groups (P = .72),

higher with the

Infants with

infants with

as was continuous

CPAP facial

Bronchiolitis: An RCT.

respiratory

CPAP application time

mask (P = .009)

(Chidini et al. 2015).

syncytial virus-

in the first 24 hours (P

mainly because

(14)

induced ARF in

= .091). Total

of intolerance (P

PICU

application time of

= .014)

Airway Pressure with

Bronchiolitis 6-12

RCT

months

1

CPAP during the PICU stay was longer with the helmet (P = .004). High-flow warm humidified oxygen versus standard low-flow nasal cannula oxygen for

202

Bronchiolitis <24 months

RCT

Standard oxygen

No reduction in length

Reduced failure

versus Nasal

of oxygen therapy

rate and

High-Flow

(primary outcome)

intensive care

1

23

Respiratory Support for Bronchiolitis moderate bronchiolitis

between the two

admission in

(HFWHO RCT): an

methods

high-flow arm

Standard oxygen

Reduced failure rate

High grade

versus Nasal

with NHF

evidence for the

open, phase 4, randomised controlled trial (Kepreotes et al, 2017) (15) A Randomized Trial of High-Flow Oxygen Therapy in Infants with

1472 Bronchiolitis < 12 months of age

RCT

High-Flow

use of NHF in

Bronchiolitis (Franklin et

general wards

al. 2018) (16)

with reduced failure of allocated treatment in the NHF arm

Table 3. Cohort studies comparing or describing practice in intensive care.

1

24

Respiratory Support for Bronchiolitis Bubble continuous

225

positive airway pressure

Bronchiolitis and

RCT

pneumonia < 5

Bubble CPAP,

Oxygen therapy

Any respiratory

NHF and SOT

delivered by bubble

support greater

Study for children with severe n

Disease yearsand

Study type and

Devices and

pneumonia and

age

design

settings

Prospective,

Description

Substantial institutional differencesmortality Identificati 3 SOT

multicentre

of clinicians

found in the use of respiratory

on of

Management for randomised controlled

observational

preference in

support methods independent of the

clinician

children withet al. 2015) trial (Chisti

study

the use of

severity of the disease

driven

Variability hypoxaemiaofin

324 Bronchiolitis

Intensive Care Bangladesh: an open,

< 24 months

bronchiolitis (Pierce et (17) al. 2015) (22)controlled Randomised trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis (Thia et al. 2008) (18)

Outcomes CPAP reduces mortality compared to

respiratory 31

Bronchiolitis < 12

in versus Cross-oversupport CPAP

months

RCT

Key than standard

1

LOE

results oxygen improves

preference Infants on CPAP

s in CO2 Improved

PICUstandard (16 oxygen

showed a greater

respiratory clearance with

hospitals) in PICU

reduction in CO2

CPAPsupport

levels

methods that are not necessaril

1

25

Respiratory Support for Bronchiolitis Heliox therapy in

312

bronchiolitis: phase III

Bronchiolitis < 12

RCT

months

SOT versus

No differences found

In mild y patient

Heliox

in the length of

bronchiolitis centred.

multicenter double-blind 107 Bronchiolitis Non-invasive

Retrospective

Report of a

treatment The intubation rate was reduced

randomizedascontrolled ventilation primary

< 12 months

observational

period when

during NIV period (p < 0.001). Norequirement, requireme

trial (Chowdhury al. ventilatory supportetfor

of age

no NIV was

children had ventilator-associated helioxntdoes of

2013) (19) infants with severe

used versus a

pneumonia (VAP) during NIV

bronchiolitis

period when

but not period compared to nine during IVbreathing ventilation

(Javouhey et al. 2008)

NIV was

period (p <0.05). The length of

Neurally triggered (23)

30

Bronchiolitis

without oxygen Reduced

design in ventilator adjusted ventilation breaths were similar reduce trigger

delay and improve

PICU

improve work of invasive

length of therapy

support ventilator assist

1

delay, improve

ventilator response Infants with severe times 133 RSV

Comparison

One unit uses

ventilator response nCPAP was associated with a shorter

nCPAP

in ventilatedsyncytial infants with respiratory

Bronchiolitis

between two

IMV only,

times, and maysupport after duration of respiratory

should be

bronchiolitis et virus needed (Clement less

< 6 months

PICUs

the other

work adjustingdecrease for severity ofof the disease

used over

nasal continuous

3

Cross overprimary Neurally hospital stay Neurally and the triggered duration of

breaths reduce trigger

al. 2011) (21) ventilator time with

1

nCPAP as the

breathing in children

IMV as

with bronchiolitis.

the

3

26

Respiratory Support for Bronchiolitis Pilot study airways pressure of vapotherm then

19

Bronchiolitis

oxygen delivery invasive mechanical in

Small single primary Comparison

No difference in

primary

center RCT support between high-

physiological and

respiratory support

moderately(Borckink ventilation severe

flow and head

other outcome

bronchiolitis et al. 2014) (24) (Hilliard et

box oxygen

parameters between

al. 2012) (54) Improved clinical and

Historical

CPAP and

NHF therapy andofSOT The introduction and use CPAP as

The

comparison

IMV in PICU

a primary support mode significantly

calculated

severe bronchiolitis

reduced LOS from 7.4 ± 5.7 to 5 ±

health care

with pre-emptive

3.9 days

costs were

economic outcomes in

525 Bronchiolitis < 3 months

nCPAP ventilatory

approxima

strategy (Essouri et al.

tely A$ 1

2014) (25)

M/year

Increase in use of non- 520 Bronchiolitis invasive ventilation for infants with severe

Observational

NIV in a

Reduced intubation rate but longer

NIV can

tertiary PICU

overall LOS if infants failed NIV

prevent

with subsequent intubation

intubation.

bronchiolitis is

Raises the

associated with

question if

1

3

3

27

Respiratory Support for Bronchiolitis decline in intubations

NIV may

(Ganu et al. 2012)

prolong

(26)

the mechanica l support if failed, this occurred most likely in infants with preexisting risk factors

28

Respiratory Support for Bronchiolitis Reduced intubation

Introduction

The rate of intubation in infants with

of NHF

viral bronchiolitis reduced from 37%

introduction of high-

therapy in

to 7% over the observation period

flow nasal prong

PICU

corresponding with an increase in the

rates for infants after

298 Bronchiolitis

Observational

< 12 months

oxygen delivery

3

use of NHF therapy.

(Schibler et al. 2011) (9) High flow nasal

Introduction

Following the introduction of NHF,

of NHF

only 9% of infants admitted to the

infants with

therapy in

PICU with bronchiolitis required

bronchiolitis

PICU

intubation, compared with 23% in

cannulae therapy in

115 Bronchiolitis < 24 months

Observational

(McKiernan et al.

the prior season (P=.043). The

2010) (27)

median PICU length of stay decreased from 6 to 4 days after the introduction of NHF therapy.

3

29

Respiratory Support for Bronchiolitis High-flow nasal

54

Bronchiolitis

Observational

PICU

NHF therapy was successful in most

cannula use in a

(79% of

patients. Most failures occurred

paediatric intensive

reported

within 8.25 hours.

care unit over 3 years

patients)

(Wraight & Ganu, 2015) (28) High flow nasal

112 Bronchiolitis

Observational

NICU

Reduced intubation and ventilation

Study

rate after introduction of NHF

supports

cannula oxygen

in <28 days

retrospective

therapy in the

neonates

and prospective

use of

study

NHF in

treatment of acute bronchiolitis in

very

neonates (Bermudez

young

et al. 2016) (29)

infants/ne

3

onates High-flow nasal cannula (HFNC)

793 Respiratory insufficiency

Use of NHF

NHF therapy was increasingly used

therapy

and was not inferior to low-flow

3

30

Respiratory Support for Bronchiolitis support in inter-

of which

during

oxygen or NIV during transportation

hospital transport of

57% were

transport

of the critically ill child

critically ill children

bronchiolitis

(Schlapbach et al.

< 2 years of

2014) (30).

age

31

Respiratory Support for Bronchiolitis Table 4. Cohort studies comparing or describing practice in general wards and emergency departments

Study

Disease and

Study type and

Devices and

age

design

settings

Bronchiolitis

Prospective

General

4 x greater likelihood of ICU

Describes

cannula oxygen

in infants <

cohort

wards

admission in the SOT

safety

therapy for infants

12 months

comparison

Retrospective

Emergency

With the introduction of a NHF

Study

department

protocol and use the intubation rate

High-flow nasal

n

61

Outcomes

Key

LOE

results 2

with bronchiolitis: pilot study. (Mayfield et al. 2014) (33) Use of high-flow

204 Infants with

nasal cannula support

bronchiolitis

in the emergency

described as

department reduces

part of a

the need for intubation

larger study

in pediatric acute

cohort

dropped from 21% to 10%.

3

32

Respiratory Support for Bronchiolitis respiratory insufficiency. (Wing et al. 2012) (34) High-flow nasal

80

Bronchiolitis

Prospective

Emergency

Demonstrates feasibility of the use of

cannula oxygen for

< 12 months

observational

department

NHF

bronchiolitis in a

of age

study

and general

pediatric ward: a pilot

3

ward

study. (Bressan et al. 2013) (35) Effect of a hospitalwide high-flow nasal

290 Bronchiolitis

Retrospective

General

Comparing 2 groups, the median

wards

LOS was significantly reduced (4

cannula protocol on

days vs 3 days; P < .001), as was the

clinical outcomes and

median total hospital charges ($12

resource utilization of

257 vs $9337; P < .001). After

bronchiolitis patients

starting NHF therapy use on the

admitted to PICU

wards, 30% of patients initially

3

33

Respiratory Support for Bronchiolitis (Riese et al. 2015)

admitted to the PICU were ultimately

(36)

transferred to the wards while still on NHF therapy. There was no difference in intubation rate or 30day readmission between the 2 groups

Acknowledgments: We thank Professor John Fraser for his mentorship to the first author over the course of her PhD studies.

Respiratory Support for Bronchiolitis

34

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