Burden of Disease and Change in Practice in Critically Ill

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Burden of Disease and Change in Practice in Critically Ill

Transcript Of Burden of Disease and Change in Practice in Critically Ill

European Respiratory Journal

Burden of Disease and Change in Practice in Critically Ill Infants with Bronchiolitis

Journal: European Respiratory Journal

Manuscript ID ERJ-01648-2016.R1

Manuscript Type: Original Article

Date Submitted by the Author: 21-Jan-2017

Complete List of Authors:

Schlapbach, Luregn; University of Queensland, Paediatric Critical Care Research Group, Mater Research Institute Straney, Lahn; Monash University Gelbart, Ben; Royal Children's Hospital Melbourne Alexander, Jan; Lady Cilento Children's Hospital Franklin, Donna; University of Queensland, Paediatric Critical Care Research Group, Mater Research Institute Beca, John; Starship Children's Health Whitty, Jennifer; University of Queensland Ganu, Subodh; Royal Adelaide Hospital Wilkins, Barry; Children's Hospital at Westmead Slater, Anthony; Lady Cilento Children's Hospital Croston, Elizabeth; Princess Margaret Hospital for Children Erickson, Simon; Princess Margaret Hospital for Children Schibler, Andy; Paediatric Critical Care Research Group, Paediatric Intensive Care Unit

Key Words: bronchiolitis, infants, intensive care, ventilation, noninvasive ventilatory support

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European Respiratory Journal
Burden of Disease and Change in Practice in Critically Ill Infants with Bronchiolitis
Luregn J Schlapbach1,2,3*, Lahn Straney4*, Ben Gelbart5,6, Janet Alexander7,8, Donna Franklin1, John Beca9, Jennifer A. Whitty10,11, Subodh Ganu12,13, Barry Wilkins14, Anthony Slater2, Elizabeth Croston15, Simon Erickson15, Andreas Schibler1,2 on behalf of the Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and the Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group
*LJ Schlapbach and L Straney contributed equally to this manuscript
1Paediatric Critical Care Research Group, Mater Research Institute, The University of Queensland, Brisbane, Australia 2Paediatric Intensive Care Unit, Lady Cilento Children’s Hospital, Brisbane, Australia 3Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Switzerland 4Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia 5Paediatric Intensive Care Unit, The Royal Children’s Hospital, Melbourne, Australia 6Melbourne Children’s Research Institute, Melbourne Australia 7Australian and New Zealand Paediatric Intensive Care Registry, CORE, Lady Cilento Children’s Hospital Brisbane, Brisbane, Australia 8School of Medicine, The University of Queensland, Brisbane, Australia 9Paediatric Intensive Care Unit, Starship Children`s Hospital, Auckland, New Zealand 10School of Pharmacy, The University of Queensland, Brisbane, Australia
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11Health Economics Group, Norwich Medical School, University of East Anglia,

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Norwich, United Kingdom

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12University of Adelaide, Adelaide, Australia

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13Paediatric Intensive Care Unit, Women’s and Children’s Hospital, Adelaide,

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Australia

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14Paediatric Intensive Care Unit, Children’s Hospital Westmead, Sydney, Australia

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15Paediatric Intensive Care Unit, Princess Margaret Hospital for Children, Perth,

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Australia

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Correspondence:

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Luregn J. Schlapbach, MD, FCICM

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Paediatric Critical Care Research Group, Mater Research Institute, The University of

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2289 Queensland

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Paediatric Intensive Care Unit, Lady Cilento Children’s Hospital

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South Brisbane QLD 4101 Australia

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Phone

..61 (07) 3068 1111

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email [email protected]

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Running Title: Severe Bronchiolitis in Critically Ill Children

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Word count text: 2990

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4489 This article has an online data supplement

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Take home message: Thresholds to admit bronchiolitis patients to PICU have

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changed over the past decade with a major impact on costs and resource utilization.

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European Respiratory Journal
Authors and Contributions: Dr. Schlapbach and Dr. Straney had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Schlapbach was responsible for the study design, prepared the first manuscript draft and approved the final version. Drs Straney and Schibler were involved in study design, analyses, preparation of the first manuscript draft and final version. Dr. Slater led the design and maintenance of the ANZPIC Registry since inception, was involved in study design, and approved the final version. Dr. Whitty and Mrs Franklin performed healthcare cost related analyses and interpretation. Drs Beca, Wilkins, Erickson, Croston, Gebhard, Ganu, and Mrs Alexander were involved in study design, data collection, and manuscript preparation, and approved the final version.
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ABSTRACT

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Bronchiolitis represents the most common cause for non-elective admission to

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pediatric intensive care units (ICUs).

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We assessed changes in admission rate, respiratory support, and outcomes of

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infants <24 months with bronchiolitis admitted to ICU between 2002 and 2014 in

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Australia and New Zealand.

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During the study period, bronchiolitis was responsible for 9,628 (27.6%) of 34,829

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non-elective ICU admissions. The estimated population-based ICU admission rate

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due to bronchiolitis increased by 11.76/100,000 each year (95%-CI 8.11-15.41). The

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proportion of bronchiolitis patients requiring intubation decreased from 36.8% in

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2002, to 10.8% in 2014 (adjusted OR 0.35; 0.27-0.46), whilst a dramatic increase in

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high-flow nasal cannula therapy use to 72.6% was observed (p<0.001). We observed

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2289 a considerable variability in practice between units, with six-fold differences in risk-

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adjusted intubation rates which were not explained by ICU type, size, nor major

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patient factors. Annual direct hospitalization costs due to severe bronchiolitis

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increased to over US$30 M in 2014.

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In conclusion, we observed increasing health care burden due to severe bronchiolitis,

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with a major change in practice in the management from invasive to non-invasive

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support suggesting thresholds to admit bronchiolitis patients to ICU have changed.

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Future studies should assess strategies for management of bronchiolitis outside

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ICUs.

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Abstract Word count: 199

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Keywords: infant; ventilation; bronchiolitis; intensive care; high-flow nasal cannulae

Abbreviations:

OR

Odd’s ratio

PICU

Paediatric Intensive Care Unit

PIM

Paediatric Index of Mortality

IV

Invasive ventilation

NIV

non-invasive ventilation

CPAP

continuous positive airway pressure

BIPAP

biphasic positive airway pressure

HFNC

high-flow nasal cannulae

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Introduction

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Bronchiolitis is a common viral lower respiratory tract infection in infants

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characterized by acute small airway inflammation, and represents the leading cause

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for hospital admission during the first year of life[1]. In high income countries,

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approximately one out of eight infants hospitalized with bronchiolitis require

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admission to Intensive Care Units (ICU) for respiratory support as a result of

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progressive respiratory distress with respiratory failure and hypoxemia[2, 3]. Despite

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a general trend towards a reduction in hospital admissions overall, bronchiolitis-

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related hospitalization costs have recently increased amounting to US$1.73 billion

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per year in the US[4]. In the past decades, pharmacological interventions have failed

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to show any benefit, and as a result, consensus guidelines emphasize supportive

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considered the cornerstone of treatment for severe bronchiolitis in ICU, over recent

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years, an increasing number of single center studies have reported benefits

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associated with early use of non-invasive ventilation (NIV) and High-Flow Nasal

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Cannula (HFNC) therapy to reduce the need for intubation and IV in bronchiolitis[9-

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13].

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The aims of this study were to describe the population-based admission rate and

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severity of bronchiolitis in infants in Australia and New Zealand admitted to intensive

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admission rate, management, outcome and associated direct health care costs over

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a 13 year period from 2002-2014.

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Methods (see as well Online Supplementary Material)
A multicenter, binational, retrospective study of all patients reported to the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry[14]. The study was approved by the Human Research and Ethics Committee (Mater Health Services HREC, Brisbane, Australia) including waiver of informed consent. The ANZPIC Registry prospectively records demographics, physiologic variables at admission, intensive care support, diagnoses and outcomes of PICU and general ICU admissions in children <16 years of age in Australia and New Zealand[14], and captures 92-94% of all pediatric ICU admissions. Inclusion and Exclusion Criteria: Infants aged <729 days and admitted with a diagnosis of bronchiolitis[8] and who were admitted to a pediatric ICU (PICU) or a general ICU in Australia or New Zealand between 1st January 2002 and 31st December 2014 were included. Elective admissions were excluded and infants with preexisting tracheostomies were excluded. Outcomes and definitions: The primary outcome was defined as the proportion of infants requiring intubation and invasive ventilation (IV). Non-invasive ventilation (NIV) was defined as continous positive airway pressure (CPAP) with or without pressure support delivered through a nasal mask, full-face mask, or a nasopharyngeal tube. Mechanical ventilation was defined as either IV and/or NIV. Since 2010, the ANZPIC registry has been prospectively recording the use of highflow nasal cannulae oxygen (HFNC) therapy. HFNC was defined as > 1L/kg/min flow of a gas oxygen mixture through nasal cannula, and was coded separately from mechanical ventilation support [12, 13]. Data analyses were therefore separated into two periods: a period before widespread use of HFNC therapy (2002-2009) and a period post widespread introduction of HFNC therapy (2010-2014). With the
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exception of one PICU, HFNC was not routinely used in the main PICUs and ICUs

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prior to 2010.

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Cost estimates methodology are provided in the Supplementary Material.

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Statistics:

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Data are presented as percentages and numbers or means with standard deviation.

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T-tests were used to compare subgroups. Population-based admission rate

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estimates were calculated. We assessed linear trends in respiratory support over the

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13-year period. In addition, trends during the 13-year study period were assessed by

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comparing risk-adjusted need for invasive ventilation. We constructed a multivariate

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prediction model for the need for invasive ventilation. For multivariable models, all

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significant predictors from the univariable analyses were used. We used a backward

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p>0.05.

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All PICUs in Australia and New Zealand contributed to the ANZPIC registry for the

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entire duration of the study period. The number of general ICUs contributing to the

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registry increased from 6 to 19 during the study period. In order to account for

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potential reporting bias, the following predefined subgroup analyses were performed:

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i) specialized pediatric ICUs (PICUs); ii) general (mixed adult and pediatric) ICUs; iii)

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pediatric and general ICUs that had been contributing for the entire length of the

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study period to the ANZPIC registry.

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All analyses were conducted using Stata (version 12.1, Stata Corp, College Station,

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Texas, USA). P-values less than 0.05 were considered significant.

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Results
During the study period, Bronchiolitis was the most common cause of ICU admission, and was responsible for 9,628 (27.6%) of 34,829 non-elective admissions in infants below two years of age. 324 infants with tracheostomies in situ at time of admission were excluded. Prematurity (20 %), chronic respiratory conditions (10%) and congenital cardiac disease (7 %) were the most common underlying conditions (Table 1). During 2010 to 2014 (post widespread introduction of HFNC), 5670 infants were admitted with bronchiolitis in comparison to 3634 during 2002 to 2009 (Table 2). In recent years, infants with bronchiolitis admitted to ICU were older, less likely to retrieved, more likely to be admitted to a general ICU, and less likely to have underlying diseases (p<0.001). The average severity of disease as measured by PIM2 decreased significantly, and ICU and hospital LOS decreased accordingly. The crude mortality over the entire study period was 0.38% (35/9304). The re-calibrated PIM2 standardized mortality ratio declined from 1.53 (0.99-2.26) in 2002-2009 down to 0.54 (0.26-0.98) in 2010-2014.
The annual number of infants with bronchiolitis admitted to ICU (including pediatric and general ICUs) increased from 383 cases in 2002 to 1528 cases in 2014 (Table 2, Figure 1). The total number of all non-elective ICU admissions per year during this time increased from 1933 to 4115. The estimated population-based age-standardised admission rate of bronchiolitis increased during the study period with an average annual increase of 11.76/100,000 infants <24 months (95%-CI 8.11 to 15.41). The change in admission rate was most pronounced in general ICUs, which took 40% of all bronchiolitis admissions requiring intensive care in 2014 (p<0.0001). The increase in admission was less marked when restricting analyses to PICUs (annual increase
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