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THE ORAL HEALTH OF CRITICALLY ILL CHILDREN Amanda Ullman B.N., Grad. Cert. PICU n5669405 A thesis submitted as partial requirement of fulfilment of a MASTERS OF APPLIED SCIENCE (RESEARCH) School of Nursing and Midwifery QUEENSLAND UNIVERSITY OF TECHNOLOGY 2009

Transcript of THE ORAL HEALTH OF CRITICALLY ILL CHILDREN -...

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THE ORAL HEALTH OF

CRITICALLY ILL CHILDREN

Amanda Ullman

B.N., Grad. Cert. PICU

n5669405

A thesis submitted as partial requirement of fulfilment of a

MASTERS OF APPLIED SCIENCE (RESEARCH)

School of Nursing and Midwifery

QUEENSLAND UNIVERSITY OF TECHNOLOGY

2009

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ABSTRACT

Introduction. In adults, oral health has been shown to worsen during critical

illness as well as influence systemic health. There is a paucity of paediatric critical

care research in the area of oral health; hence the purpose of the Critically ill

Children’s Oral Health (CCOH) study is to describe the status of oral health of

critically ill children over time spent in the paediatric intensive care unit (PICU). The

study will also examine the relationship between poor oral health and a variety of

patient characteristics and PICU therapies and explore the relationship between

dysfunctional oral health and PICU related Healthcare-Associated Infections (HAI).

Method. An observational study was undertaken at a single tertiary-referral

PICU. Oral health was measured using the Oral Assessment Scale (OAS) and

culturing oropharyngeal flora. Information was also collected surrounding the use of

supportive therapies, clinical characteristics of the children and the occurrence of

PICU related HAI.

Results. Forty-six participants were consecutively recruited to the CCOH

study. Of the participants 63% (n=32) had oral dysfunction while 41% (n=19)

demonstrated pathogenic oropharyngeal colonisation during their critical illness. The

potential systemic pathogens isolated from the oropharynx and included Candida sp.,

Staphylococcus aureus, Haemophilus influenzae, Enterococcus sp. and Pseudomonas

aeruginosa. The severity of critical illness had a significant positive relationship

(p=0.046) with pathogenic and absent colonisation of the oropharynx. Sixty-three

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percent of PICU-related HAI involved the preceding or simultaneous colonisation of

the oropharynx by the causative pathogen.

Conclusion. Given the prevalence of poor oral health during childhood critical

illness and the subsequent potential systemic consequences, evidence based oral

hygiene practices should be developed and validated to guide clinicians when nursing

critically ill children.

KEYWORDS

Oral health, oropharyngeal colonisation, oral hygiene, paediatrics, critical illness,

paediatric intensive care, healthcare-associated infection.

FUNDING ATTRACTED BY THE RESEARCH PROGRAMME

Nursing Research Projects Grant, Royal Children’s Hospital Foundation

$23,500.

Novice Researcher Grant, Australian College of Critical Care Nurses $5,000.

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TABLE OF CONTENTS

ABSTRACT .............................................................................................................. II

KEYWORDS ............................................................................................................ III

FUNDING ATTRACTED BY THE RESEARCH PROGRAMME ....................... III

TABLE OF CONTENTS ........................................................................................ IV

STATEMENT OF ORIGINAL AUTHORSHIP .................................................. VIII

LIST OF ABBREVIATIONS .................................................................................. IX

ACKNOWLEDGEMENTS ..................................................................................... XI

CHAPTER 1 INTRODUCTION ................................................................................. 1

1.1 INTRODUCTION .................................................................................................... 1

1.2 PURPOSE OF THE RESEARCH ................................................................................ 4

1.3 SIGNIFICANCE OF STUDY........................................................................................5

1.4 SUMMARY ............................................................................................................. 5

CHAPTER 2 LITERATURE REVIEW ...................................................................... 6

2.1 INTRODUCTION .................................................................................................... 6

2.2 LITERATURE SEARCH STRATEGIES ....................................................................... 6

2.3 ORAL HEALTH ...................................................................................................... 7

2.3.1 Physiology of the oral cavity ......................................................................... 7

2.3.2 The ‘dysfunctional’ oral cavity ................................................................... 10

2.4 CRITICAL ILLNESS IN CHILDHOOD ..................................................................... 12

2.4.1 PICU population ......................................................................................... 12

2.4.2 Measuring critical illness in childhood ...................................................... 14

2.4.3 The effect of PICU therapies on oral health ............................................... 16

2.4.4 The oral health of the critically ill .............................................................. 17

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2.4.5 Current oral hygiene practices ................................................................... 21

2.5 HEALTHCARE-ASSOCIATED INFECTION (HAI) ................................................... 25

2.5.1 Pneumonia .................................................................................................. 25

2.5.2 Bacteraemia and blood-stream infections .................................................. 27

2.6 CURRENT LIMITATIONS IN LITERATURE .............................................................. 29

2.7 SUMMARY: WHAT THE LITERATURE SUGGESTS .................................................. 31

CHAPTER 3 METHODS ......................................................................................... 32

3.1 INTRODUCTION ................................................................................................... 32

3.2 RESEARCH DESIGN .............................................................................................. 32

3.3 RESEARCH QUESTIONS ........................................................................................ 33

3.4 STUDY SETTING AND POPULATION ...................................................................... 34

3.5 SAMPLING STRATEGY AND SIZE ........................................................................... 35

3.6 DATA COLLECTION ............................................................................................. 36

3.6.1 Oropharyngeal cultures .............................................................................. 36

3.6.1.1 Saliva sampling .................................................................................... 37

3.6.1.2 Laboratory protocol ............................................................................. 39

3.6.2 Instruments ................................................................................................ 41

3.6.2.1 Oral Assessment Scale (OAS) .............................................................. 41

3.6.2.2 Pediatric Logistic Organ Dysfunction score (PELOD) and Paediatric

Indicator of Mortality 2 (PIM2) ....................................................................... 45

3.6.2.3 Clinical Pulmonary Infection Score (CPIS) ........................................ 46

3.6.2.4 Data extraction tool ............................................................................. 47

3.8 DATA ANALYSIS ................................................................................................... 48

3.9 ETHICAL CONSIDERATIONS ................................................................................. 52

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3.9.1 Informed Consent ........................................................................................ 52

3.9.2 Risk management procedures ..................................................................... 53

3.9.3 Confidentiality and security ........................................................................ 54

CHAPTER 4 RESULTS ........................................................................................... 55

4.1 INTRODUCTION .................................................................................................. 55

4.2 CHARACTERISTICS OF PARTICIPANTS ................................................................. 55

4.3 DATA ANALYSIS .................................................................................................. 58

4.4.1 What is the status of oral health in critically ill children during admission

to a PICU? ........................................................................................................... 61

4.4.2 How does the oral health of critically ill children change during their

admission to PICU? ............................................................................................. 65

4.4.3 Is the oral health of critically ill children affected by patient characteristics

or PICU therapies? .............................................................................................. 68

4.4.4 Is there a relationship between dysfunctional oral health in critically ill

children and PICU-related healthcare-associated infections (HAI)? ................. 69

CHAPTER 5 DISCUSSION ..................................................................................... 75

5.1 INTRODUCTION .................................................................................................. 75

5.2 KEY FINDINGS .................................................................................................... 76

5.2.1 What is the status of oral health in critically ill children during admission

to a PICU? ........................................................................................................... 76

5.2.2 How does the oral health of critically ill children change during their

admission to PICU? ............................................................................................. 79

5.2.3 Is the oral health of critically ill children affected by patient characteristics

or PICU therapies? .............................................................................................. 81

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5.2.4 Is there a relationship between dysfunctional oral health in critically ill

children and PICU-related healthcare-associated infections (HAI)? ................. 83

5.3 STRENGTHS AND LIMITATIONS OF THE STUDY ................................................... 86

5.5 SUMMARY .......................................................... ERROR! BOOKMARK NOT DEFINED.

CHAPTER 6 CONCLUSION .................................................................................. 90

6.1 INTRODUCTION ................................................................................................... 90

6.4 CONCLUSION ....................................................................................................... 94

REFERENCES ........................................................................................................... 95

APPENDICES .......................................................................................................... 101

ORAL ASSESSMENT SCALE (OAS) .......................................................................... 101

PEDIATRIC LOGISTIC ORGAN DYSFUNCTION SCORE (PELOD) .............................. 102

PAEDIATRIC INDEX OF MORTALITY 2 (PIM2) ........................................................ 103

CLINICAL PULMONARY INFECTION SCORE (CPIS) ................................................ 104

DATA EXTRACTION TOOL ....................................................................................... 105

ETHICAL APPROVAL FROM ROYAL CHILDREN’S HOSPITAL, BRISBANE HREC ...... 107

ETHICAL APPROVAL FROM THE QUEENSLAND UNIVERSITY OF TECHNOLOGY HREC

................................................................................................................................ 108

PARENT / GUARDIAN INFORMATION AND CONSENT FORMS ..................................... 110

YOUTH ASSENT INFORMATION AND CONSENT FORMS ............................................. 114

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STATEMENT OF ORIGINAL AUTHORSHIP

The work contained in this thesis has not been previously submitted to meet

requirements for an award at this or any other higher education institution. To the best

of my knowledge and belief, the thesis contains no material previously published or

written by another person except where due reference is made.

_______________________________________

Amanda Ullman

_______________________________________

Date

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LIST OF ABBREVIATIONS

ACCCN = Australian College of Critical Care Nurses

ANOVA = Analysis of Variance

ANZPICR = Australia and New Zealand Paediatric Intensive Care Registry

ARDS = Acute Respiratory Distress Syndrome

CCOH = Critically ill Children’s Oral Health

CDC = Centers for Disease Control and Prevention

CP = Cerebral Palsy

CFU = Colony Forming Units

CINAHL = Cochrane Library and Cumulative Index to Nursing and Allied Health

CO2 =Carbon Dioxide

CPIS = Clinical Pulmonary Infection Score

CVVHD = Continuous Veno-Venous Haemo-Dialysis

ECMO = ExtraCorporeal Membrane Oxygenation

ETT = Endo-Tracheal Tube

FiO2=Fraction of Inspired Oxygen

HAI = Healthcare-associated infection

HBA = Horse Blood Agar

HREC = Human Research Ethics Committee

ICU = Intensive Care Unit

IgA = Immunoglobulin A

IgM = Immunoglobulin M

INR=International Normalised Ratio

kPa = Kilopascal

LVAD = Left Ventricular Assist Device

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MAC = MacConkey’s Agar

mmHg = Millimetres of mercury

mmol/l = Millimols per litre

MSA = Mannitol Salt Agar

O2 = Oxygen

OAS = Oral Assessment Scale

PaCO2=Arterial Carbon Dioxide Pressure

PaO2=Arterial Oxygen Pressure

PELOD = Pediatric Logistic Organ Dysfunction Score

PICU = Paediatric Intensive Care Unit

PIM2 = Paediatric Index of Mortality

RBWH = Royal Brisbane and Women’s Hospital

RCH = Royal Children’s Hospital, Brisbane

SAB = Sabouraud Dextrose Agar

SBP = Systolic Blood Pressure

SD = Standard Deviations

SPSS = Statistical Package for Social Sciences

VAP = Ventilator associated pneumonia

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ACKNOWLEDGEMENTS

Like many people completing post-graduate work, this Master’s thesis has been a

labour of love.

Thank you to the Royal Children’s Hospital Foundation and the Australian College of

Critical Care Nurses (ACCCN) for the financial support to complete this project.

Thank you to the wonderful nurses at the Royal Children’s Hospital, Paediatric

Intensive Care Unit (PICU), for letting me add to your already busy days and the

support of my Nurse Unit Managers. It is great to work with a group of professionals

who are focused on providing quality, evidence-based, holistic care. A big thanks to

Debbie for pushing me in this path, one simple literature review just keeps getting

bigger.

Thank you to my family for their support - my husband, for letting me off house-

painting duties, and my dad for making it seem achievable and sensible.

Thank you also to my supervisory team, Dr Peter Lewis and Prof. Glenn Gardner.

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CHAPTER ONE - INTRODUCTION

1.1 INTRODUCTION

Critically ill children experience physiological changes which result in instability and

acute crises, requiring intensive nursing care to support single organ or systemic

dysfunction. The treatment modalities used to support children experiencing critical

illness and the progression of critical illness may result in dysfunction within the oral

cavity. In a healthy child, the oral cavity harbours over 250 strains of commensal

bacteria (O'Reilly, 2003) which change in response to numerous factors including the

child’s general health and well-being. The changes generated by critical illness may

produce an imbalance of commensal oral bacteria, which allows the oral cavity to

become a haven for potential systemic pathogens (Fourrier, Duvivier, Boutigny,

Roussel-Delvallez, & Chopin, 1998). Due to the anatomical connection between the

oral cavity and the respiratory and circulatory systems, pathogens colonising the

oropharynx could potentially transfer to cause systemic infections (Munro, Grap,

Elswick et al., 2006).

In the paediatric intensive care environment, respiratory and blood-stream infections

caused by fungal and bacterial pathogens are associated with substantial financial,

morbidity and mortality costs (Inwald, Tasker, Peters, & Nadel, 2009; Rubenstein,

Kabat, Shulman, & Yogev, 1992; Safdar, Dezfulian, Collard, & Saint, 2005; Singhi,

Raman Rao, & Chakrabarti, 2008; Suljagic et al., 2005; Thorburn et al., 2009; Turton,

2008). However, research describing the prevalence of fungal and bacterial pathogens

in the oropharynx and their systemic effects during critical illness in children is

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scarce. In comparison, adult critical care research has recognised the impact that poor

oral health may have on the morbidity and mortality outcomes of these patients

(Abele-Horn et al., 1997; A. Berry & Davidson, 2006; A. Berry, Davidson, Masters,

& Rolls, 2007; Binkley, Furr, Carrico, & McCurren, 2004; Brennan et al., 2004;

Chan, Ruest, O'Meade, & Cook, 2007; Cutler, 2005; Ewig et al., 1999; Fitch, Munro,

Glass, & Pellegrini, 1999; Fourrier et al., 1998; Garrouste-Orgeas et al., 1997; Grap,

Munro, Ashtiani, & Bryant, 2003; D. Jones & Munro, 2008; H. Jones, 2005; Kite &

Pearson, 1995; McNeill, 2000; Munro & Grap, 2004; Munro, Grap, Elswick et al.,

2006; O'Reilly, 2003; Pugin, Auckenthaler, Lew, & Suter, 1991; Ross & Crumpler,

2007; Scannapieco, Stewart, & Mylotte, 1992; Somerville, 1999; Stiefel, Damron,

Sowers, & Velez, 2000). This research is now focussing on treatment strategies which

can be used to improve oral health during critical illness. Interest in the systemic

effects of oral health during paediatric critical illness is growing, with a recent

publication by Thorburn et al., (2009) which examined the carriage of abnormal

bacterial flora and antibiotic resistant flora in the pharynx and gut of children with

cerebral palsy requiring mechanical ventilation, and their associated infection rates.

The study also found that in 65% of children with cerebral palsy requiring mechanical

ventilation who developed an infection, the infecting pathogen was carried in the

patients’ pharynx on admission or in their gut flora, and concluded that early targeted

antibiotic therapy may be beneficial.

Within paediatric and adult critical care practice, pneumonia is acknowledged as

being a major threat to mechanically ventilated patients (Chan et al., 2007; Safdar et

al., 2005; Schleder, 2003; Turton, 2008) . The relationship between poor oral health,

in the form of pathogenic oropharyngeal colonisation, and hospital-acquired

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pneumonia, especially ventilator-associated pneumonia (VAP), has been well

documented in robust adult critical care clinical research (Bonten et al., 1994; Ewig et

al., 1999; Fourrier et al., 1998; Garrouste-Orgeas et al., 1997; Munro & Grap, 2004;

Pugin, Auckenthaler, Lew et al., 1991). Pathogenic microflora that have been isolated

in the dental and oropharyngeal flora of critically ill adults, that are also potential

microbial causative agents of pneumonia include - Staphylococcus aureus,

Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa and

Acinetobacter baumannii (Ewig et al., 1999; Fourrier et al., 1998; Munro & Grap,

2004). Aspiration of pathogenic microorganisms from the oropharynx whilst

intubated is a substantial risk factor and contributes to the development of VAP

(Bonten et al., 1994; Ewig et al., 1999; Fourrier et al., 1998; Garrouste-Orgeas et al.,

1997; Munro & Grap, 2004; Pugin, Auckenthaler, Lew et al., 1991). The risk factors,

progression and consequences of pathogenic colonisation of the oropharynx during

childhood critical illness have not been thoroughly described in previous research.

Hence the purpose of the Critically ill Children’s Oral Health (CCOH) study is to

describe the status of pathogenic colonisation of the oropharynx, within the context of

oral health, in critically ill children.

Traditionally, oral health and oral hygiene have been given low priority in the nursing

care of a critically ill child. Oral hygiene is often neglected or performed inadequately

by swabbing the children’s mouths for comfort. Currently, within the Paediatric

Intensive Care Unit (PICU) at the Royal Children’s Hospital (RCH) no oral hygiene

protocol exists to guide nursing practice. Previous researchers in critical care have

suggested that nursing practice surrounding oral hygiene is often based on tradition,

individual preferences, availability of products, anecdotal or subjective evaluation (A.

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Berry et al., 2007; Gibson & Nelson, 2000; McNeill, 2000), rather than evidence-

based protocols. No evidence-based oral hygiene protocol has been researched,

validated and made available to guide clinicians when nursing critically ill children.

The aim of this study therefore is to contribute to the body of knowledge available

surrounding the oral health of critically ill children, so that this information can be

used in further research to develop evidence-based guidelines.

1.2 PURPOSE OF THE RESEARCH

The purpose of the CCOH study is to describe the status of oral health in critically ill

children. In addition, the study will examine the influence of time in the PICU, patient

characteristics and PICU therapies on the status of oral health. It will also explore the

link between poor oral health and PICU-acquired Healthcare-Associated Infections

(HAI). To meet this purpose, the study will answer the following questions:

1) What is the status of oral health in critically ill children during admission to a

PICU?

2) How does the oral health of critically ill children change during their admission to

PICU?

3) How is the oral health of critically ill children affected by patient characteristics or

PICU therapies?

4) What is the relationship between dysfunctional oral health in critically ill children

and PICU-related HAI?

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1.3 SIGNIFICANCE OF THE STUDY

Previous research has determined that adults who are critically ill are at an increased

risk for developing systemic infections when they have poor oral health (Fourrier et

al., 1998; Munro, Grap, Elswick et al., 2006; Scannapieco et al., 1992). Since this risk

has been established, oral hygiene protocols have been developed to improve the oral

health of critically ill adults, endeavouring to decrease the risk of developing systemic

infections. However, current literature surrounding the oral health of critically ill

children is scarce. Before developing strategies to promote and improve oral health

during a child’s critical illness, baseline research needs to be undertaken to explore

the current state of oral health, the risk factors for developing poor oral health and the

subsequent effect on systemic health. The purpose of this study is to provide this

baseline research which may then be used to develop strategies which focus on

children with an increased risk for poor oral health and potential systemic

consequences. This study is significant as evidence-based guidelines can then be

developed and tested for efficiency and effectiveness in improving the oral and

systemic health of critically ill children.

1.4 SUMMARY

This thesis provides details of the study carried out at the PICU at the RCH, Brisbane,

which aimed to describe the oral health of critically ill children. It is structured over

six chapters to provide information surrounding the literature review and

methodological approach to support the study and the results, conclusions and clinical

implications of the study.

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CHAPTER 2 - LITERATURE REVIEW

2.1 INTRODUCTION

This chapter reviews the existing literature surrounding the oral health of critically ill

children. It discusses components of oral health, critical illness in childhood, and

Healthcare-Associated Infections (HAI).

2.2 LITERATURE SEARCH STRATEGIES

A literature search was undertaken using the electronic databases of PubMed,

Medline, the Cochrane Library and the Cumulative Index to Nursing and Allied

Health (CINAHL) using MeSH headings and free text words. Articles that resulted

from the search were screened with the inclusion criteria of (1) oral health in critical

illness (2) oropharyngeal colonisation (3) human subjects (4) adult or child subjects

and (5) publication in English. The following terms were used individually and in

various combinations in the search process - oral health, oropharyngeal colonisation,

critical illness, critical care, intensive care, children, pediatrics, paediatrics, oral

hygiene, nosocomial, healthcare associated infection. The reference lists of published

materials were also hand searched for additional information. The aim was to identify

all relevant randomised controlled trials, observational studies as well as discussion

documents. Due to a lack of available research surrounding the oral health of critically

ill children, the search was widened to incorporate adult literature and literature dating

before 1999.

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2.3 ORAL HEALTH

2.3.1 Physiology of the oral cavity

The oral cavity works in a state of equilibrium, functioning to aid in digestion,

communication and respiration and aims to protect the body from exogenous sources.

Structurally it is primarily made up of mucosal membranes - lips, gums, tongue,

buccal cheek, roof, and saliva, with teeth developing in early childhood (Munro,

Grap, Jablonski, & Boyle, 2006). The oropharynx of a healthy person is colonised by

greater than 250 different groups of microorganisms (O'Reilly, 2003) with the

majority of microorganisms living in symbiosis with the host, and are referred to as

commensal flora.

The acquisition of commensal oropharyngeal flora occurs within the first 18 hours

after birth (Kite & Pearson, 1995), dominated by viridans streptococci such as

Streptococcus oralis, Streptococcus mitis, and Streptococcus salivarius (Jenkinson &

Lamont, 2005; Kononen, 2000; Law, Seow, & Townsend, 2007; Marsh & Percival,

2006). The diversity of the oropharyngeal flora increases over time and between one

to seven months of age, Gram-negative anaerobes establish, with the most common

being Prevotella melaninogenica, Fusobacterium nucleatum and Veillonella spp

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(Kononen, 2000; Kononen, Kanervo, Takala, Asikainen, & Jousimies-Somer, 1999;

Marsh & Percival, 2006).

Oropharyngeal flora change composition throughout childhood, with the eruption of

primary teeth having a great influence of the oral environment by providing suitable

niches for colonisation (Kononen, Asikainen, Karjalainen, & Jousimies-Somer, 1994).

This process leads to an increase in the number and complexity of the commensal

microflora in the oral cavity. Bacteria are the predominant commensal

microorganisms found in the mouth, and a diverse range of gram positive and gram

negative species can be isolated including Streptococcus sanguis, Staphylococcus sp.,

Veillonella sp., Neisseria sp., Actinomyces sp. and Lactobacillus sp. (Law et al.,

2007). In addition, yeasts, mycoplasmas and protozoa can occasionally be isolated

(Marsh & Percival, 2006). The commensal flora act directly as an important

component of the host defences by being a significant barrier to exogenous

populations (Marsh & Percival, 2006). The oropharyngeal microflora are not static,

but change in composition over age and in response to the individual’s physical state,

including their health (Roberts, 1998).

Saliva production has an important role in maintaining health and stability within the

oral cavity (Munro, Grap, Jablonski et al., 2006) as it contains several components

that are important in suppressing bacterial and fungal colonisation, serving both anti-

plaque producing and antibacterial roles (Kite & Pearson, 1995; Stiefel et al., 2000).

Saliva coats the mucous membranes, aids in digestion, regulates the pH of the mouth

and contains calcium and phosphate to maintain dental integrity (O'Reilly, 2003). In a

clean, healthy mouth, salivary proteins and glycoproteins form a film (pellicle) which

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acts as a protectant for the teeth and contains immune components including

immunoglobulin A (IgA), immunoglobulin M (IgM) and lactoferrin, which protect the

oral cavity from potential pathogens (Munro & Grap, 2004; Munro, Grap, Jablonski et

al., 2006; O'Reilly, 2003). Saliva also provides mechanical removal of plaque and

microorganisms as it circulates the oral cavity (Munro, Grap, Jablonski et al., 2006).

During the day, salivary flow ranges from 0.25 to 0.35 millilitres per minute when

unstimulated, to four to six millilitres per minute when stimulated (A. Berry &

Davidson, 2006). When saliva production is reduced, its multiple protectant functions

are limited.

The commensal microflora of the mouth has a beneficial role as a barrier against the

colonisation of potentially pathogenic flora. However, some of the bacteria present in

the oral cavity can cause localised infection. The most common bacterial infections in

the mouth are dental caries (Kononen, 2000). Dental caries are primarily caused by

the species Streptococcus mutans and Streptococcus sobrinus. S. mutans has been

identified as the principal cariogenic bacterium for caries initiation while S. sobrinus

is thought to enhance progression and development of caries (Law et al., 2007).

Dental plaque is a biofilm found on tooth surfaces that provides an environment for

commensal and exogenous microorganisms. The combination of bacterial colonies,

polysaccharides and salivary proteins form the mixture of polymers known as plaque

(Kite & Pearson, 1995). Plaque provides opportunity for adherence of the organisms

to either the tooth surface or other microorganisms. Calculus occurs when minerals

are deposited intracellularly and extracellularly in dental plaque (Munro & Grap,

2004). Dental plaque, calculus and dental caries are oral conditions that affect healthy

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children and adults, however in the critically ill, may potentially have systemic

consequences.

2.3.2 The ‘dysfunctional’ oral cavity

The oral cavity works in a fragile state of stability and when exogenous sources are

introduced, or the general health of the person changes, this balanced situation is

disturbed. Xerostomia is the severe reduction of saliva, manifested as a dry mouth and

can be caused by a variety of medications and Paediatric Intensive Care Unit (PICU)

therapies. Severe xerostomia is defined as an unstimulated salivary flow of less than

0.1 millilitres per minute (A. Berry & Davidson, 2006). When a patient is xerostomic,

increased levels of proteases in the mouth cause the removal of fibronectin from the

epithelial cell surface of the mucosal membranes (A. Berry et al., 2007). Fibronectin

is present on cell surfaces and acts as a reticuloendothelial-mediated host-defence

mechanism (A. Berry & Davidson, 2006). The depletion of fibronectin exposes oral

receptors and facilitates attachment of exogenous microorganisms, such as

Staphylococcus aureus, to mucosal membranes within the oropharynx. A build up of

dental plaque caused by a lack of oral hygiene can also serve as a reservoir for

pathogenic microorganisms in patients with poor oral hygiene (Fourrier et al., 1998;

Scannapieco et al., 1992). Oral mucositis - inflammation of the oral mucosa - is

characterised by erythema, oedema, bleeding, ulceration and pseudomembrane

formation within the mouth and is a painful and incapacitating side-effect of

chemotherapy and other medical conditions prevalent in critically ill children

(Donnelly, Bellm, Epstein, Sonis, & Symonds, 2003; Napenas, Brennan, Bahrani-

Mougeot, Fox, & Lockhart, 2007).

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Quantifying ‘poor’ oral health is a challenge for clinicians and researchers. Munro et

al., (2006) propose that the measurement of saliva volume, dental plaque and oral

microbial flora provide a baseline for oral health measurement. However, the

logistical issues surrounding nursing assessment of stimulated and unstimulated saliva

volumes and dental plaque make it difficult to use this as a practical oral health

measurement.

Oral assessment tools have been developed and validated for use in multiple clinical

practice areas. Landmark work regarding the assessment of oral health by nurses was

primarily accomplished by Beck (1979). The oral assessment guide was originally

developed by Eilers et al. (1988) for clinical assessment of changes in the oral cavity

of individuals receiving cancer treatment and has established considerable evidence

for its validity and reliability in other clinical settings including the PICU (Andersson,

Persson, Hallberg, & Renvert, 1999; Barnason et al., 1998; Eilers, Berger, & Peterson,

1988; Ferozali, Johnson, & Cavangnaro, 2007; Holmes & Mountain, 1993; Jiggins &

Talbot, 1999). It involves assessment of five categories: lips, tongue, saliva, mucous

membranes/gingivae and teeth.

However oral assessment tools, including those by Beck (1979) and Eilers et al.,

(1988) do not incorporate the microbial changes occurring in the mouth. Considering

the relationship between microbial flora changes and oral health, this is an important

element of oral health to measure in research.

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2.4 CRITICAL ILLNESS IN CHILDHOOD

2.4.1 PICU population

Children admitted to a PICU are a heterogeneous population of patients (Franklin,

Senior, James, & Roberts, 2000). Many children are pre-morbidly healthy, while

others have an acute episode related to a pre-existing condition. Critically ill children

sometimes require rescue-therapy in the form of complicated and invasive respiratory,

cardiovascular and renal support, while some simply require post-operative

monitoring.

The diversity in critically ill children is illustrated by the manner in which they are

admitted to the PICU and the conditions which require admission. Data retrieved from

the Australia and New Zealand Paediatric Intensive Care Registry (2008) reports that

nearly 44% of all PICU admissions in 2006 in Australia and New Zealand were

elective, that is the admission followed elective surgery, elective PICU procedure or

was required for elective monitoring (Alexander, Tregea, & Slater, 2008). The most

common diagnostic group was post operative (non-cardiac), with 24.3% requiring

admission to the PICU, followed by cardiovascular (23.3%), respiratory (22.7%),

miscellaneous (12.9%), neurological (7.6%), injury (7.3%), and gastrointestinal or

renal (1.9%) (Alexander et al., 2008). Depending on the PICU site, the percentage of

ventilated patients ranged from 4.8% to 85% (Alexander et al., 2008). The majority of

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admissions to PICU were for children less than five years of age (65%), with infants

less than 12 months making up more than half this group (38.8% of all PICU

admissions) (Alexander et al., 2008). This diversity in age, severity, cause and

treatment of paediatric critical illness, may also be reflected in the oral health of

critically ill children.

Both the mechanism of critical illness and the baseline physiological function and

health of critically ill children are very different to critically ill adults. This is

demonstrated in their oral health. As described previously, oral health changes over

age, especially with the genesis of teeth and the resultant change in the microbial

environment. Within critical care, two examples of differences between adult and

paediatric patients are crude mortality rates and length of Intensive Care Unit (ICU)

stay. The length of stay for children admitted to ICU’s is varied, but universally

shorter than adults (ANZICS: Adult patient database, 2008), with the majority of

children staying less than two days (Alexander et al., 2008). The crude mortality rate

for children admitted to Australian and New Zealand PICUs in 2006 was 2.9%, with

neonates recording the highest age specific mortality (4.2%) (Alexander et al., 2008).

Adult ICUs have varying crude mortality rates, however they are collectively higher

than PICUs (ANZICS: Adult patient database, 2008; Fitch et al., 1999). Health

professionals and researchers agree that the universal application of adult research to

the paediatric population is not ideal given the differences between these two

populations. However, despite numerous differences between adults and children and

a consequential understanding that a majority of adult research should not be

transposed to a paediatric setting, adult research may well contribute to ideas,

thoughts and research methodologies with a paediatric focus. Additionally, while

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adult research has the capacity to influence paediatric research within the area of oral

health research, blanket application of adult research to the paediatric population

should be regarded with caution.

2.4.2 Measuring critical illness in childhood

Children admitted to a PICU have widely varying levels of critical illness, and the

challenge lies with researchers to find a tool to quantify these levels for use in

research. Measuring critical illness effectively and reliably is important when

researching a diverse group, such as critically ill children. Critical illness scores allow

researchers to examine critical illness as a potential factor contributing to changing

oral health.

The Pediatric Logistic Organ Dysfunction Score (PELOD) (Lacroix & Cotting, 2005;

Leteurtre et al., 1999; Leteurtre et al., 2003; Santanae, Leite, de Carvalho, & Lopes,

2009; Thukral, Kohli, Lodha, Kabra, & Kabra, 2007; Yung, Wilkins, Norton, &

Slater, 2008) is a measure of severity of multiple organ dysfunction syndrome. It is

calculated for each patient by adding the scores for six individual organ systems based

on the recorded levels of the variables included in the systems, after stratifying into

age categories. The PELOD has been validated for repeated measures (Leteurtre et

al., 2003) showing the changing severity of organ dysfunction during an individuals’

critical illness.

While frequently used in other paediatric critical care studies (Lacroix & Cotting,

2005; Leteurtre et al., 1999; Leteurtre et al., 2003; Santanae et al., 2009; Thukral et

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al., 2007; Yung et al., 2008), a major criticism of the PELOD score is that a majority

of the elements do not take into consideration the contribution of PICU therapies (e.g.

renal replacement) to improve scores. This means the PELOD score may be unfairly

low for patients who have early interventional therapies implemented by the PICU

treating team.

The Paediatric Index of Mortality 2 (PIM2) is a regression model that uses admission

data to predict intensive care outcome for children (Baghurst, Norton, & Slater, 2008;

Eulmesekian, Perez, Minces, & Ferrero, 2007; Inwald et al., 2009; Shann, Pearson,

Slater, & Wilkinson, 1997; Slater, Shann, & Pearson, 2002; Thukral, Lodha, Irshad, &

Arora, 2006; Wolfer, Silvani, Musicco, & Salvo, 2007). It was initially designed to

compare the standard of care between PICUs and within PICUs over time (Slater et

al., 2002), but is also commonly used to estimate mortality risk within groups of

patients in research (Slater et al., 2002). The PIM2 is a revision of the original PIM

(Shann et al., 1997) using expanded and updated data from 14 intensive care units:

eight in Australia, four in the UK and two in New Zealand.

The PIM2 model shows a Hosmer-Lemeshow goodness-of-fit of 8.14, with 8 df,

p=0.420 (Slater et al., 2002). The performance for the 14 ICUs showed the area under

the receiver operating characteristic plot ranged from 0.78 to 0.95 (Slater et al., 2002).

The ten variables in the PIM2 model were included only because they improved the

discrimination or calibration of the model (Slater et al., 2002). The model uses

physiological data, including systolic blood pressure and pupillary responses and

patient data, including admission to PICU, for the purposes of estimating recovery

post procedure, and presence of high risk/low risk diagnosis, to generate an overall

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risk-score. However, the PIM2 is reflective of the patients’ mortality risk on

admission to PICU only, and is not designed to be used to describe individual

patients.

2.4.3 The effect of PICU therapies on oral health

Critical illness and admission to PICU require life-saving supportive therapies which

sometimes have an adverse effect on components of oral health. Most critically ill

children are restricted in their fluid intake to maximise respiratory, renal and cardiac

function (Jiggins & Talbot, 1999; Kite & Pearson, 1995), which then reduces salivary

flow. Clinical conditions which cause dehydration, such as fever, diarrhoea, and

burns, also cause a reduction of salivary volume (O'Reilly, 2003). Several

medications which are commonly used in PICU can also lead to diminished salivary

production including anticholinergics, diuretics, antiemetics, opioid analgesics and

retinoids (Kite & Pearson, 1995). Any interruption in saliva production due to

dehydration or drug therapy, can lead to infection of the salivary glands by the

oropharyngeal flora (Kite & Pearson, 1995) and alter the ability of the oral cavity to

respond to the introduction of exogenous, and potentially pathogenic microorganisms

(Munro, Grap, Jablonski et al., 2006).

Other drugs are also associated with alterations in the physiology of the mouth.

Phenytoin, a common anti-seizure medication, is associated with swelling and

hypertrophy of the gingivae (Kite & Pearson, 1995). Antibiotics are associated with a

suppression in commensal bacterial numbers in the mouth (Sixou, Medeiros-Batista,

& Bonnaure-Mallet, 1996), allowing for an overgrowth by previously minor drug-

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resistant components of the microflora, or colonisation by exogenously-acquired (and

often pathogenic) micro-organisms (Marsh & Percival, 2006). Patients receiving

radiotherapy, chemotherapy or high doses of antineoplastic drugs are at very high risk

of oral mucositis which manifests as ulceration, xerostomia and secondary infection

of the oral cavity (White, 2000).

An unconscious or intubated child is unable to speak, eat or drink, which limits the

production and movement of saliva around the mouth (Kite & Pearson, 1995). The

endotracheal tube (ETT) presents a source of pressure for the oral cavity (Barnason et

al., 1998), especially in non-dentate patients where the tube rests on the gingivae

rather than on the teeth (D. Jones & Munro, 2008). The orally intubated patient is

forced to keep their mouth open for extended periods. Even when not intubated, the

patients are often exposed to high flow facial oxygen and oral suctioning causing

drying of the mucosa. Critically ill children regularly receive a combination of these

therapies and develop these clinical conditions, which may potentially have an effect

on their oral health.

2.4.4 The oral health of the critically ill

Critically ill children are at high risk of developing poor oral health because of their

clinical condition and the therapies instituted or continued within the PICU. However,

studies describing the oral health of this group are scarce. Franklin et al. (2000)

conducted an observational cohort study examining the oral health status of children

in the PICU and measured oral health by plaque accumulation, gingival inflammation

and gingival bleeding. The study involved 54 participants, however excluded all non-

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dentate patients (mean age 4.8 years ± 4.3) which, as previously described, excludes

the majority of patients admitted to a PICU. Measurements of oral health were only

conducted on admission and discharge, and the outcomes were primarily focused on

investigating the efficacy of the oral care that they received while admitted to PICU,

rather than the participants’ oral health throughout their critical illness. They found a

statistically significant increase in mean plaque scores during PICU stay (admission =

22.5; discharge 25.8; p=0.001) and gingival inflammation (admission = 4.1; discharge

5.5; p=0.006). However, they did not examine oropharyngeal colonisation during

PICU admission or the relationship between the children’s oral health and their

clinical condition or PICU therapies.

Previous research authored by Jiggins and Talbot (1999) involved the implementation

a mouth care guideline within their PICU, however they did not carry out any baseline

or post implementation oral health measurement. Within their prospective descriptive

study to evaluate the frequency and route of endotracheal colonisation of intubated

children, Rubenstein et al (1992) described the colonisation of the buccal mucosa

(cheek). Only recruiting patients who were to be intubated for greater than five days,

and excluding patients less than one month of age, restricted their sample size to 19

patients. The pathogens that they cultured from the buccal mucosa included Candida

albicans and other Candida species, Enterococcus sp., Staphylococcus aureus,

Pseudomonas sp., Acinetobacter sp., Klebsiella sp., Haemophilus influenzae,

Enterobacter sp. and Escherichia coli. Patients who were colonised with Candida sp.

were sicker (Pediatric Risk of Mortality: 12.9 ± 2.8 vs. 4.9 ± 1.0; p=0.01). The study

did not examine the oral health of the children within their critical illness, and was

limited due to its poor sample size and the inclusion of patients who only received

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prolonged intubation and ventilation, which is not descriptive of the entire PICU

population.

Recently, Thorburn et al. (2009) compared the prevalence of ‘abnormal’ and

antibiotic-resistant bacterial flora in children with cerebral palsy (CP) (n=53)

requiring mechanical ventilation, to critically ill children without CP (n=257). Within

their prospective, cohort study, they found that 89% of children with CP, carried

abnormal bacterial flora or potential pathogens, compared to 55% of children without

CP (RR=2.09 (CI 1.76-2.48)). Pseudomonas, Klebsiella, Enterobacter and

Citrobacter species were the most common potential pathogens. Other oral health

measurements were not collected and an analysis of the effect of other clinical

characteristics and PICU therapies was not carried out.

The majority of existing studies available describing the oral health of critically ill

patients are based on adult critical care. These studies provide paediatric critical care

providers with information to develop research and guide clinical practice where

paediatric research is not available. For example, landmark work was accomplished

by Scannapeico et al. (1992) when they conducted a case-control study describing the

prevalence of dental plaque and colonisation of that dental plaque by potential

respiratory pathogens. Thirty-four critically ill adults were compared to 25 healthy

patients who attended a preventative dentistry clinic. Scannapeico et al. (1992) found

a statistically significant higher mean plaque score for critically ill participants (1.9 ±

0.2) than the control group (1.4 ± 0.1; p=<0.005). They also found that 64.7% of ICU

patients were colonised in their teeth or oral mucosa by respiratory pathogens in

comparison to 16% of the control (p= <0.005). The respiratory pathogens colonised

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included Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae,

Serratia marcescens and Escherichia coli.

These findings have been confirmed in other studies. Fourrier et al. (1998) examined

the dental status, prevalence of pathogenic colonisation in dental plaque and dental

plaque as a source of Healthcare-Associated Infection (HAI) in adult ICU patients. In

their prospective observational cohort study of 57 participants, they found a

statistically significant increase in dental plaque on patients remaining in ICU for five

days or greater (day 0: 1.1 ± 0.7; day 5: 1.6 ± 0.7; p<0.05). Dental colonisation by

respiratory pathogens showed an increasing trend with length of admission, however

due to the small sample size it did not reach statistical significance. Fourrier et al.

(1991) cultured similar pathogens to the study carried out by Scannapeico et al.

(1992), but also discovered Candida albicans. A positive bacterial plaque sample on

admission to the ICU showed a sensitivity of 0.47 and specificity of 0.92 (p<0.005) of

developing a HAI.

In an observational cohort study, Munro et al., (2006) examined the oral health status

of 66 critically ill adults through assessment of the oral cavity using a visual analogue

scale, culture of an oral specimen, measurement of salivary volume and analysis of

salivary immune components; IgA and lactoferrin. The association between oral

health and Ventilator-Associated Pneumonia (VAP) was also determined using the

Clinical Pulmonary Indicator Score (CPIS). They found a trend of worsening oral

health over time in ICU, evidenced by an increasing amount of plaque and a reduction

in salivary flow, however it did not reach statistical significance (Munro, Grap,

Elswick et al., 2006). Salivary volume did decrease in volume over length of ICU stay

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(p=0.003). There was no discussion on specific organisms present on oral or tracheal

cultures (Munro et al. 2006).

The change in oropharyngeal colonisation over time spent in adult ICU was also

described by Garrouste-Orgeas et al., (1997). Their descriptive study found acquired

colonisation of the oropharynx by systemic bacterial pathogens such as Acinetobacter

baumannii, Klebsiella Pneumoniae, Enterobacteriaceae, Pseudomonadaceae, S.

aureus, Enterococcus spp. in 44 of 86 (51%) patients. The median time for

oropharyngeal colonisation was seven days.

Baseline oral health research is necessary in paediatric critical care in order to inform

practice surrounding the provision of oral hygiene. Despite the dearth of paediatric

literature in this area, to rely on adult research to inform paediatric practice would be

problematic. Differences between adult and paediatric populations lie not only in

their oral health, but also the nature and duration of their critical illness.

2.4.5 Current oral hygiene practices

Critically ill children are dependent on healthcare workers to provide all aspects of

their oral care. However, a number of authors suggest that oral care regimens are

often based on tradition, individual preferences, availability of products, anecdotal

and subjective evaluation rather than evidence-based protocols (A. Berry et al., 2007;

Gibson & Nelson, 2000; McNeill, 2000). Within the PICU at the Royal Children’s

Hospital (RCH), Brisbane, there is no standard or protocol to guide nursing practice

for oral care. In recent years, researchers have focused on developing evidence-based

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protocols for the oral care of critically ill adult patients (Cutler, 2005; Ferozali et al.,

2007; Ross & Crumpler, 2007; Stiefel et al., 2000), however few have been proven to

be effective (Chan et al., 2007).

Oral health is assisted by mechanical and chemical cleansing. The use of a toothbrush

to clean the teeth and gums has been widely accepted as a simple and efficient method

of mechanically removing plaque and debris (Kite & Pearson, 1995; O'Reilly, 2003).

Despite these recommendations, many dentate patients in PICUs have their oral care

carried out with the use of foam or cotton swabs alone, rather than with toothbrushes

(Binkley et al., 2004; Costello & Coyne, 2008; Rello et al., 2007a). A large

percentage of critically ill children are non-dentate and protocols incorporating this

into guidelines are scarce. The physical design of cotton swabs suggests that they may

break-down while in the mouth, leaving cotton filaments which may then be micro-

aspirated.

There is a large variety of chemicals used in the prevention and treatment of poor oral

health. Chlorhexidine gluconate mouthwash is an anti-plaque agent which maintains

oral health through its ability to suppress overgrowth with Gram-positive and Gram-

negative bacteria as well as yeasts, making it useful in the prevention of the

development of plaque (A. Berry et al., 2007; Kite & Pearson, 1995; O'Reilly, 2003).

Chlorhexidine fixes to the surface of oral structures and is slowly released for up to 24

hours, requiring infrequent applications. A large volume of data is available

surrounding the use of chlorhexidine for oral decontamination, which has been

summarised in a recent meta-analysis by Chan (2007). Seven randomised controlled

trials totalling 2144 patients, using chlorhexidine in varying forms (0.12%, 0.2%, 2%)

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showed a significant reduction in oropharyngeal colonisation (RR 0.46, 0.39 to 0.81;

p=0.002; I2=48.2%), however a majority of these trials have taken place in adult

cardiothoracic Intensive Care Units, so the application of such research to general

critical care (Chan et al., 2007), and specifically the PICU, is questionable.

There is scarce literature surrounding the safety and effectiveness of other solutions

including sodium bicarbonate, toothpaste, normal saline, tap water, and sterile water

(A. Berry et al., 2007) as oral cleansers. An early study examining hydrogen peroxide

found it was effective in improving the condition of oral mucosa (Passos & Brand,

1966), however subsequent research found it to be associated with mucosal

abnormalities and poor subjective reports by participants (Tombes & Galluci, 1993).

Lemon and glycerol has been associated with xerostomia and erosion of the tooth

enamel (A. Berry et al., 2007; Stiefel et al., 2000). The optimal frequency of oral

hygiene provision is also in dispute, with recommended frequencies ranging from

hourly, to twice daily (A. Berry et al., 2007; Chan et al., 2007; Grap, Munro,

Elswick, Sessler, & Ward, 2004; Tombes & Galluci, 1993). Small sample sizes,

subjective measurements, lack of adequate controls and poor interventional control is

present in the majority of research surrounding the provision of oral hygiene, which

makes it difficult to confidently apply these in the clinical setting.

The only published study available regarding the institution of an oral health guideline

on PICU patients was conducted by Jiggins and Talbot (1999). They developed a

guideline consisting of regular oral assessment which directed the use of different

products including toothbrush and toothpaste, Nystatin (an oral anti-fungal

medication), 3% hydrogen peroxide diluted 50:50 with water, and an artificial saliva

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spray. They stated that there was some controversy with the choice of solutions and

implements, but did not provide any information regarding the effectiveness of the

protocol. Considering the lack of research to support elements within the guidelines

and the effectiveness of the guideline as a whole, it is not appropriate to institute this

as an evidence-based protocol.

The application of oral health research requires the cooperation and adoption by

clinical staff. Descriptive studies conducted by Fitch et al., (1999), Rello et al., (2007)

and Binkley et al., (2004) surveyed intensive care nurses throughout America and

Europe. They identified that while nurses recognise the importance of oral hygiene

practices, they may be hesitant to provide oral care to patients who are intubated

because ETTs may limit access to the oral cavity and they fear dislodging or

displacing the tube. The adult critical care nurses did not rate it as a high priority or as

essential when taking care of critically ill patients. The majority of those surveyed did

not currently follow an evidence-based pathway for oral care. However, none of these

studies surveyed PICU nurses, so it is not necessarily reflective of current PICU

practice or PICU nursing attitudes.

Although the provision of oral hygiene in the intensive care has been recognised as

being a priority by international health-care bodies, including the Centers for Disease

Control and Prevention (CDC) (Tablan, Anderson, Besser, Bridges, & Hajjeh, 2003),

there is a paucity of literature surrounding the effectiveness and appropriateness of

oral hygiene practices in adult and paediatric intensive care.

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2.5 HEALTHCARE ASSOCIATED INFECTION (HAI)

HAI’s are a significant cause of mortality and morbidity for critically ill children

(Inwald et al., 2009; Rubenstein et al., 1992; Safdar et al., 2005; Singhi et al., 2008;

Suljagic et al., 2005; Thorburn et al., 2009; Turton, 2008), and were previously

known as ‘nosocomial infections’ (Garner, Jarvis, Emori, Horan, & Hughes, 1996).

As part of the National Healthcare Safety Network for the Centers for Disease Control

and Prevention (CDC), Horan, Andrus, & Dudeck (2008, pg. 309) define HAI’s as “a

localised or systemic condition resulting from an adverse reaction to the presence of

an infectious agent(s) or its toxin(s) . There must be no evidence that the infection was

present or incubating at the time of admission to the acute care setting”.

Within the scope of this study, interest is in infections acquired within the PICU,

which may be inferred as being a result of a patient’s clinical condition or their care

during admission in the PICU. A HAI is considered acquired in the PICU if the

clinical condition fulfilling the criteria develops after the patient was in the PICU for

two days and within two days after discharge (Horan et al., 2008). The most common

and clinically significant HAI within the PICU population are pneumonia (Schleder,

2003; Turton, 2008) and blood-stream infection (D. Jones & Munro, 2008) .

2.5.1 Pneumonia

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Within adult critical care research, the relationship between poor oral health in the

form of pathogenic oropharyngeal colonisation, and hospital-acquired pneumonia,

especially VAP, has been well documented in robust clinical research (Bonten et al.,

1994; Ewig et al., 1999; Fourrier et al., 1998; Garrouste-Orgeas et al., 1997; Munro &

Grap, 2004; Pugin, Auckenthaler, Lew et al., 1991). The pathogenic microflora that

have been isolated in the dental and oropharyngeal flora of critically ill adults, that are

also potential microbial causative agents of VAP include Staphylococcus aureus,

Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa and

Acinetobacter baumanni (Ewig et al., 1999; Fourrier et al., 1998; Munro & Grap,

2004).

Pneumonia and VAP remain leading causes of morbidity and mortality among

mechanically ventilated adults (Schleder, 2003; Turton, 2008), with an incidence

ranging from 9-27%, crude mortality that may exceed 50% and estimated costs of

greater than $10,000-$20,000 per incident (Chan et al., 2007; Safdar et al., 2005).

Ventilator-associated pneumonia (VAP) has been difficult to define, however there is

general consensus on defining it as a pneumonia that develops 48 hours or more after

intubation with an endotracheal or tracheostomy tube, and was not present before

intubation (Feider, 2007; Garner et al., 1996; Munro, Grap, Elswick et al., 2006;

Pugin, Auckenthaler, Miller et al., 1991; Safdar et al., 2005). VAP is a multifaceted

pathophysiological phenomenon that develops when normal pulmonary or host

defence mechanisms are either overwhelmed or impaired by endotracheal tube

insertion and mechanical ventilation (Feider, 2007; Horan et al., 2008; Rello et al.,

2007a). Pneumonia is an inflammatory response to the presence and multiplication of

microorganisms that have invaded the lower respiratory tract (Feider, 2007). The

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Clinical Pulmonary Infection Score (CPIS) has been used by multiple researchers

(Aydogdu & Gursel, 2008; McClure et al., 2009; Munro, Grap, Elswick et al., 2006;

Sakaquicki, Shime, S., & Hashimoto, 2008; Singh, Gayowski, Wagener, & Marino,

1999) to measure clinically evident pneumonia and VAP. The clinical diagnosis

combines body temperature, white blood cell count, appearance of tracheal secretions,

oxygenation requirements, infiltrates on chest x-ray and cultures of tracheal aspirate

to give a cumulative score. Using a CPIS of greater than six as clinical definition of

pulmonary infection in ventilated patients has shown a strong correlation (r = 0.84; p

<0.001) (Pugin, Auckenthaler, Miller et al., 1991) with the ‘gold standard’ of

quantitative culture of either bronchoscopic or non-bronchoscopic broncho-alveolar

lavage fluid, with sensitivity of 73-93% (A'Court et al., 1993) and a specificity of 84-

100% (A'Court et al., 1993).

In PICU research, there is a paucity of research available regarding VAP and its

relationship with poor oral health and pathogenic oropharyngeal colonisation.

Rubenstein et al., (1992) established a link between pathogenic colonisation of the

buccal mucosa and colonisation of the ETT, however they did not measure the

incidence of pneumonia within the sample. A recent literature review compiled by

Turton (2008) regarding VAP in PICU, comprised primarily adult critical care data.

Their extrapolation suggests the institution of adult-designed interventions, however

baseline data examining the prevalence of VAP and its relationship to poor oral health

does not exist in paediatrics.

2.5.2 Bacteraemia and blood-stream infections

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In the highly vascular environment of the oral cavity, tissue destruction, such as

ulceration, can provide direct communication of pathogenic microorganisms to the

circulatory system (Kite & Pearson, 1995; Stiefel et al., 2000). There is substantial

evidence that bacteraemia occurs in healthy populations with manipulation of the oral

mucosa, such as with tooth brushing (D. Jones & Munro, 2008). Procedures that

manipulate the oral mucosa in critically ill children are frequent, including intubation,

oral suctioning and oral hygiene practices. Bloodstream infection represents the

failure of the immune system to contain infection at a focal site and the consequent

occurrence of disseminated disease.

Bacteraemia has been defined as the presence of viable bacteria within the circulating

blood (Daly, Mitchell, Grossberg, Highfield, & Stewart, 1997; D. Jones & Munro,

2008) and can result in blood stream infection. Blood-stream infection is a frequent

and challenging HAI and accounts for 15% (D. Jones & Munro, 2008) of HAI’s. In

the adult population, the crude mortality rate of hospital-acquired blood stream

infections is approximately 35%, with a range from 12% to 80% (D. Jones & Munro,

2008). Blood-stream infections have been shown to increase ICU and hospital stay,

the use of healthcare resources and significantly increase morbidity and mortality (D.

Jones & Munro, 2008).

In accordance with the CDC (Horan et al., 2008), within this study the diagnosis of

blood-stream infection is established with presence of the following criteria: a

recognised pathogen cultured from one or more blood cultures, where the organism

cultured from the blood is not related to an infection at another site (Horan et al.,

2008). If the pathogen is a common skin contaminant (e.g. S. epidermis), the

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participant must have at least one of the following signs or symptoms; temperature

>38oC or <36oC (if less than one year old), hypotension, chills or bradycardia or

apnoea (if greater than one year old).

Little research exists around the prevalence of bacteraemia or blood-stream infections

caused by microorganisms originating in the oropharynx in paediatrics. In adults,

there have been increasing rates of bloodstream infections related to organisms such

as Staphylococcus aureus, Enterococcus sp., coagulase-negative Staphylococci and

Candida sp. (Hugonnet, Sax, Eggimann, Chevrolet, & Pittet, 2004; D. Jones &

Munro, 2008; Suljagic et al., 2005; Zolldann, Thiex, Waitschies, Lutticken, &

Lemmen, 2005), all of which are known to colonise the oropharynx in times of critical

illness.

2.6 CURRENT LIMITATIONS IN THE LITERATURE

Research describing the oral health of critically ill children is limited to a small group

of paediatric studies and extrapolations from adult literature. A study by Franklin et

al., (2000), within the PICU, excluded all non-dentate patients - who make up a large

percentage of critically ill children - and did not describe oropharyngeal colonisation.

They also did not examine the diversity of oral dysfunction caused by variations in

patient characteristics or PICU therapies. Jiggins and Talbot’s (1999) study did not

measure oral health, but discussed it as being poor and requiring an evidence-based

guideline for intervention. The study by Rubenstein et al., (1992) describing the

relationship between ETT colonisation and buccal mucosa flora was limited to a small

sample (n=19), all of whom were intubated for greater than five days, which is not

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reflective of all critically ill children. They also did not measure oral health as a

whole. Thorburn et al’s (1999) study did not collect information regarding oral health

measurement outside of oropharyngeal flora, and only examined children who were

mechanically ventilated. Additionally, extrapolation from adult literature, while useful

to develop practice and research methodologies, should be universally applied with

caution considering both the differences in baseline oral health and the mechanism of

critical illness between the two groups.

There is a lack of research regarding the prevalence and consequences of VAP and its

relationship with poor oral health and pathogenic oropharyngeal flora in critically ill

children. There is also a paucity of research regarding the prevalence and

consequences of bacteraemia and blood-stream infections caused by microorganisms

originating in the oropharynx in paediatrics. Considering the mortality, morbidity and

economic consequences of VAP and blood-stream infection in the adult ICU, this

needs to be addressed.

There is also a lack of information regarding current PICU practice surrounding the

completion of oral hygiene. Adult literature has reported a gap between current

practice and evidence-based guidelines, however there is no information available

regarding paediatrics.

Research regarding all elements of the oral health of critically ill children, systemic

consequences of poor oral health in PICU and current oral hygiene practices in PICU

are scarce and poorly completed. Considering the significance and consequences of

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the studies completed in adult ICU on the same topic, research in the oral health of

critically ill children would appear necessary.

2.7 SUMMARY: WHAT THE LITERATURE SUGGESTS

In summary, the literature provides clear direction for future PICU oral health

research.

The physiology of the oral cavity functions in fragile stability and disturbances

by exogenous or internal sources may cause imbalances in the commensal

flora.

Critically ill children receive therapies and have clinical conditions which may

alter the health of the oral cavity.

The scant literature addressing paediatric oral health suggests paediatric oral

health may worsen or change over admission to a PICU.

Adult literature has established that during critical illness oral health worsens

and the commensal oropharyngeal flora can change to potentially pathogenic

flora.

Within adults, pathogenic oropharyngeal and dental flora is significantly

associated with HAI including pneumonia.

VAP and blood-stream infections are associated with significant economic

costs and mortality and morbidity outcomes.

There are no published evidence-based guidelines for the provision of oral

hygiene in PICU.

In the adult ICU, nurses do not rate oral hygiene as being a critical element of

nursing care.

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CHAPTER 3 - METHODS

3.1 INTRODUCTION

This study was designed to describe the status of oral health in critically ill children

and to examine the influence of time in the Paediatric Intensive Care Unit (PICU),

patient characteristics and PICU therapies on the status of oral health. It also explored

the link between poor oral health and PICU-acquired Healthcare-Associated

Infections (HAI). To fulfil these aims a prospective observational cohort design was

used. This chapter describes the research design, research questions, population and

sample, instruments, data analysis and ethical issues in the study.

3.2 RESEARCH DESIGN

The Critically ill Children’s Oral Health (CCOH) study used a prospective

observational cohort design (Bhopal, 2008; Friis & Sellers, 2009). The study’s

purpose was to describe the status of oral health in critically ill children which was

supported by the cohort design. In addition, the study examined the influence of time

in the PICU, patient characteristics and PICU therapies on the status of oral health. It

also explored the link between poor oral health and PICU-acquired HAI. The

prospective cohort design was chosen to support these research questions as it

provides strong evidence of association in comparison to other observational designs

(Bhopal, 2008).

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An observational cohort design is a epidemiological study design commonly used

throughout paediatric (Bracken et al., 2009; Edwards, Powell, Mason, & Oliver, 2009;

Franklin et al., 2000; Sullivan et al., 2005; Veldman, Trautschold, Weiss, Fischer, &

Bauer, 2006), critical care (Edwards et al., 2009; Fourrier et al., 1998; Franklin et al.,

2000; Munro, Grap, Elswick et al., 2006; Veldman et al., 2006) and oral health

(Fourrier et al., 1998; Franklin et al., 2000; Munro, Grap, Elswick et al., 2006)

research. The goal of analytical observational study designs is to add to a body of

knowledge, test hypotheses, generate new hypotheses and suggest mechanisms of

causation (Friis & Sellers, 2009). The prospective cohort design supports the research

objectives within this study as it facilitates exploration, description and causation

(Aschengrau & Seage, 2008; Friis & Sellers, 2009). It also provides information about

the characteristics of a study population over a period of time.

3.3 RESEARCH QUESTIONS

1) What is the status of oral health in critically ill children during admission to a

PICU?

2) How does the oral health of critically ill children change during their admission to

PICU?

3) How is the oral health of critically ill children affected by patient characteristics or

PICU therapies?

4) What is the relationship between dysfunctional oral health in critically ill children

and PICU-related HAI?

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3.4 STUDY SETTING AND POPULATION

The study was conducted at the PICU at the Royal Children’s Hospital (RCH),

Brisbane in Australia. This unit provides an eight bed tertiary level PICU for children

of Queensland, Northern New South Wales and adjacent states and countries. There

are 600-700 admissions per year, of which 40% require mechanical ventilation

(Alexander et al., 2008). All modes of intensive supportive care are provided

including nitric oxide therapy, continuous veno-venous haemo-dialysis (CVVHD),

high frequency oscillation ventilation but excluding extracorporeal membrane

oxygenation (ECMO), left ventricular assist device (LVAD), and cardiac bypass

surgery. A tertiary PICU is a specialist referral centre for children needing intensive

care and provides complex, multi-system life support for an indefinite period for

children less than 16 years of age (Joint Faculty of Intensive Care Medicine, 2003).

The population under investigation was critically ill children admitted to the PICU at

the RCH. Children admitted to the PICU are a heterogeneous population of patients

(Franklin et al., 2000) experiencing physiological instability requiring intensive

support. They are referred from many specialities, in particular respiratory medicine,

neurosurgery, orthopaedic, surgery and oncology/haematology (Franklin et al., 2000).

Admissions are sourced from multiple locations; specifically the RCH Department of

Emergency Medicine, RCH inpatient acute-care wards, operating theatres and outside

hospital referrals via the RCH retrieval service. Diagnoses include respiratory

illnesses such as bronchiolitis, multi-traumas including severe head injury, and

oncological conditions requiring multi-system support.

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3.5 SAMPLING STRATEGY AND SIZE

All patients admitted to the PICU at the RCH, Brisbane within a seven month period

were screened for potential participation by the principal investigator or trained PICU

personnel. After satisfying the inclusion/exclusion criteria, informed consent was

obtained by the principal investigator or trained PICU personnel. A consecutive

sample was then recruited to the study.

Inclusion Criteria:

Admission to the PICU at the RCH, Brisbane,

Clinical condition suggesting a PICU stay greater than or equal to 48 hours

(Fourrier et al., 1998),

Recruitment, first oropharyngeal saliva sampling and oral assessment within

12 hours of admission to PICU (Fourrier et al., 1998; Scannapieco et al.,

1992),

All ages, that is both dentate and non-dentate,

Parental or guardian consent and youth assent where required.

Exclusion Criteria:

Patients who had undergone oral surgery or had an oral condition that required

specialised oral care (Fitch et al., 1999) for example; cleft palate repair or

oropharyngeal abscess,

Already participated in the CCOH study on a prior admission to PICU,

Parents or guardian unavailable or unable to give consent due to legal

concerns that were under the care of Child and Family Services, or lack of

English.

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The sampling framework consisted of the time period (seven months) and the

inclusion/exclusion criteria. The sample size was constrained due to the scope of a

master’s study and budget.

3.6 DATA COLLECTION

In order to answer the previously described research questions, data were collected on

the dependent and independent variables. The dependent variables used to describe

oral health within this study were pathogenic colonisation of oropharyngeal flora and

the Oral Assessment Scale (OAS) (Barnason et al., 1998; Eilers et al., 1988; Gibson &

Nelson, 2000; Jiggins & Talbot, 1999; Ross & Crumpler, 2007) The independent

variables collected were demographic, clinical and condition characteristics. A

number of instruments were used to describe the status of oral health, clinical and

condition characteristics and to extract this information.

3.6.1 Oropharyngeal cultures

The definition of ‘pathogenic’ colonisation of the oropharynx used in the CCOH

study excludes bacteria which are considered commensal in a paediatric mouth. As

with previous studies (Fourrier et al., 1998; Rubenstein et al., 1992; Scannapieco et

al., 1992; Thorburn et al., 2009) conducted within paediatrics and adults, ‘pathogens’

are listed as:

Acinetobacter spp.

Aspergillus spp.

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Candida spp.

Citrobacter diversus

Enterobacteriaceae spp.

Escherichia coli

Haemophilus influenzae

Klebsiella pneumoniae

Pseudomonas spp.

Serratia marcescens

Staphylococcus aureus

Stenotrophomonas maltophilia

Streptococcus pneumoniae

These are microorganisms that commonly cause infection or disease in critically ill

children. The micro-organisms cultured from the oropharyngeal saliva swabs were

categorised into ‘nil flora’, ‘commensal flora’ or ‘pathogenic flora’ as per these

definitions.

Saliva sampling

Participants had samples of oropharyngeal saliva collected for bacterial and fungal

culture completed within 12 hours of admission to PICU and then second daily for the

course of their admission to PICU. Fourrier et al (1998) established that salivary,

dental plaque and tracheal aspirate colonisations are closely linked, and as the

sampling was to be performed by nurses, this was judged to be the least invasive, but

most accurate method of sampling. Oropharyngeal saliva sampling was collected

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within 12 hours of admission to PICU as base-line data. A similar restriction has

previously been used by several authors (Fourrier et al., 1998; Munro, Grap, Elswick

et al., 2006; Scannapieco et al., 1992).

Other methodologically similar studies completed in an adult critical care setting

involved oropharyngeal, or equivalent, sampling on admission and then daily

(Rubenstein et al., 1992), second daily (Pugin, Auckenthaler, Lew et al., 1991), third

daily (Munro, Grap, Elswick et al., 2006; Scannapieco et al., 1992), every five days

(Fourrier et al., 1998) and weekly (Sixou, Medeiros-Batista, Ganddemer, &

Bonnaure-Mallet, 1998). The Centers for Disease Control and Prevention (CDC)

suggest that ‘most’ bacterial HAI’s become evident 48 hours or more after admission,

this being their typical incubation period (Garner et al., 1996; Horan et al., 2008).

Therefore, in order to collect the most accurate information regarding HAI,

oropharyngeal saliva sampling was collected every 48 hours.

Oropharyngeal salivary samples were obtained using a TRANSWAB® by the

participants’ PICU nurse. Nurses were trained individually by the principal

investigator and information was placed at the bedside regarding the saliva sampling

protocol. The TRANSWAB® was placed in the patient’s mouth for a period of at

least 30 seconds to allow for saliva absorption, as per the manufacturer’s instructions.

Swabs were collected at approximately the same time (1000hrs), at least two hours

after oral hygiene care or oral intake (feeds, medications, diet) (Sixou et al., 1998).

Samples were then transported to the Queensland Health Pathology Services

Laboratory within one hour of collection, for semi-quantitative analysis.

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Laboratory protocol

The oropharyngeal saliva swabs were placed into five millilitres of 0.85% saline and

vortexed for 30 seconds. Both the undiluted extract and a 106 dilution were cultured.

1uL of the undiluted extract was then plated onto the following media:

Horse Blood Agar (HBA) incubated at 35oC in Carbon Dioxide (CO2) for 48

hours

MacConkey’s Agar (MAC) incubated at 35oC in Oxygen (O2) for 48 hours

Chocolate Bacitracin Agar incubated at 35oC in CO2 for 48 hours

Sabouraud Dextrose Agar (SAB) incubated at 35oC in O2 for 48 hours

Mannitol Salt Agar (MSA) incubated at 35oC in O2 for 48 hours

These plates were chosen by a panel of microbiologists, including the Director of

Microbiology at the Royal Brisbane and Women’s Hospital (RBWH), in order to

confirm the presence of the previously identified ‘pathogenic’ organisms.

Representative colonies of all morphologic types present on the plates up to 48 hours

after inoculation were subcultured and identified by standard methods (Scannapieco et

al., 1992). Staphylococci were differentiated based on colony characteristics, mannitol

fermentation and the coagulase reaction (Scannapieco et al., 1992). No attempts were

made to identify other bacteria, legionella, mycoplasma or viruses.

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The following procedure was used to formulate the 106 dilution from the previously

vortexed material:

50 microlitres into five millilitres of saline (102)

50 microlitres of 102 into five millilitres of saline (104), then 10 uL of this 104

dilution were plated onto the same media as described above.

Cultures were then examined at 24 and 48 hours incubation. The commensal or

pathogenic flora were identified and semi-quantitated using the count table provided

(see Table 3.1).

Table 3.1 Count table for semi-quantitated analysis

Screen Colony forming units on any medium (cfu)

Count reported

Undiluted screen

>100

11-99

1-10

>105

count x 103

count x 103

Diluted screen

>100

10-100

1-10

>109

count x 106

count x 106

The diagnosis of colonisation by pathogenic organisms is based on the positive

culture of the oropharyngeal saliva swab when greater than or equal to 106 colony

forming units (cfu) per litre without signs of clinical infection (Fourrier et al., 1998).

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3.6.2 Instruments

Oral Assessment Scale (OAS)

In addition to oropharyngeal colonisation, the status of oral health during critical

illness in childhood was described using an oral assessment instrument. Few oral

assessment instruments have been specifically designed or adapted for intubated,

incommunicative or paediatric patients. Landmark work regarding the assessment of

oral health was accomplished by Beck (1979) in developing an oral assessment tool

which has been modified and improved by multiple authors in order to validate it for

different adult and paediatric population groups (Andersson et al., 1999; Barnason et

al., 1998; Eilers et al., 1988; Ferozali et al., 2007; Gibson & Nelson, 2000; Holmes &

Mountain, 1993; Jiggins & Talbot, 1999; Paulsson, Wardh, Andersson, & Ohrn, 2008;

Ross & Crumpler, 2007). The modifications and validations of the OAS are

summarised in Table 3.2.

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Table 3.2 Modifications and validations of the Oral Assessment Scale (OAS)

Authors Population Modifications Validity & Reliability testing Comments

Andersson, P., Persson, L., Hallberg, I., & Renvert, S. (1999)

Adult Oncology 7 categories (saliva, swallow, voice, gums, teeth/dentures, lips, mucous membranes)

Internal consistency: cronbach’s alpha = 0.87

Inter-rater reliability between r=0.65-0.92

Recommended to not use voice component; not a useful measurement within their study

Barnason, S., Graham, J., Wild, M., Jenson, L., Rasmussen, D., Shulz, P., et al. (1998)

Adult Critical Care

6 categories (saliva, gums, teeth/dentures, lips, mucous membranes, tongue)

Inter-rater reliability: r=0.92 Removed elements that are not assessable

Beck (1979) Adult oncology 15 categories (voice (four assessments), swallow (two assessments), saliva (two assessments), lips, tongue, mucous membranes, gingival, teeth / dentures, plaque, diet)

Nil Original

Eilers, J., Berger, A., & Peterson, M. (1988)

Adult oncology 8 categories (voice, swallow, lips, tongue, saliva, mucous membranes, gingival & teeth / dentures)

Content validity: literature review / panel of experts

Inter-rater reliability: r=0.912

High level of clinical usability, comprehensiveness, consistency

Ferozali, F., Johnson, G., & Cavangnaro, A. (2007)

Adult long-term care

4 categories (lips, oral mucosa, gingival tissues, and plaque)

Inter-rater reliability: r=>0.85

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Authors Population Modifications Validity & Reliability testing Comments

Gibson, F., & Nelson, W. (2000)

Paediatric Oncology

8 categories (voice, swallow, lips, tongue, saliva, mucous membranes, gingival & teeth / dentures) Non-dentate adaption (score 1=healthy for teeth category)

Nil

Holmes, S., & Mountain, E. (1993)

Adult Palliative Oncology

Tested Eilers (Eilers et al., 1988) & Beck (Beck, 1979) OAS

Eilers inter-rater reliability: correlation coefficient r=0.73

Beck inter-rater reliability: correlation coefficient r=0.84

Content validity by panel of experts believed Eilers’ was insufficient in detail & Becks’ was too detailed & lengthy

Jiggins, M., & Talbot, J. (1999)

Paediatric ICU 5 categories (saliva, gums, teeth/dentures, lips, mucous membranes)

Inter-rater reliability testing discussed but results not provided – reported to ‘improve’ after education

No discussion re. non-dentate assessment

Ross, A., & Crumpler, J. (2007)

Adult Critical Care

5 categories (saliva, gingiva, teeth/dentures, lips, mucous membranes)

Nil Simplification for ventilated patients

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The oral health of critically ill children was measured throughout the study by the

Oral Assessment Scale (OAS) (see Appendix A). The adaptations eliminating the

elements of voice and swallow, validated by Jiggins and Talbot (1999) and Barnason

et al (1998) were incorporated, as well as the simplification integrated by Ross and

Crumpler (2007). During critical illness, the child is frequently unconscious, unable to

communicate or developmentally immature therefore assessment procedures that

require active participation of the patient are unusable (Munro, Grap, Jablonski et al.,

2006). However, in order to ensure validity, the assessment needs to accurately

capture all of the components which are needed (Munro, Grap, Jablonski et al.,

2006), without increasing complexity.

The OAS involves assessment over five categories: lips, tongue, saliva, mucous

membranes/gingival and teeth. Three levels of descriptors are identified for each

category and the overall oral assessment score is the sum of the subscale scores. A

normal finding for a category is given a rating of one. If there is a barrier breakdown

or loss of function, the category is given a three. Accordingly, the rating of two is

used for not normal, but without barrier breakdown or loss of function. The scores

from the five categories are calculated with a normal mouth given a score of five, and

the highest possible score being 15.

The OAS is primarily an objective tool and multiple authors (Andersson et al., 1999;

Barnason et al., 1998; Eilers et al., 1988; Ferozali et al., 2007; Holmes & Mountain,

1993; Jiggins & Talbot, 1999) have previously undertaken inter-rater reliability

testing, therefore testing was not repeated. OAS was carried out by the bed-side nurse

every twelve hours, within their initial patient assessment at the commencement of

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their shift. Education was carried out by the principal investigator to the bed-side

nurses in multiple formats, describing both the OAS and the procedure for

assessment. These formats included one-on-one education sessions, presentations in

group sessions at ward meetings and handovers, posters throughout the PICU, as well

as summary information attached to the computer monitor at the bed-side and in the

participants’ bed-side folder.

Pediatric Logistic Organ Dysfunction score (PELOD) and Paediatric Indicator of

Mortality 2 (PIM2)

Two methods to measure critical illness were used in the study - the Pediatric Logistic

Organ Dysfunction Score (PELOD) (see appendix B) and the Paediatric Indicator of

Mortality 2 (PIM2) (see appendix C). This was done because of the strengths and

limitations of each instrument. Each scoring system produces composite scores, made

up of a group of variables consisting of clinical and laboratory data (Lacroix &

Cotting, 2005).

The PELOD score (Lacroix & Cotting, 2005; Leteurtre et al., 1999; Leteurtre et al.,

2003; Santanae et al., 2009; Thukral et al., 2007; Yung et al., 2008) is a measure of

the severity of multiple organ dysfunction syndrome in the PICU. It is calculated for

each patient by adding the scores for individual organ systems based on recorded

levels of variables included in the systems. Six organ systems are included:

neurological, cardiovascular, renal, respiratory, haematological and hepatic, each

containing multiple variables, totalling 12. The physiologic variables are stratified

into four age groups: neonates (less than seven days or one month of age), infants

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(one to 12 months of age), children (12 to 144 months of age) and adolescents (greater

than 144 months of age). The PELOD has been validated (Leteurtre et al., 2003) for

repeated measures showing the changing severity of organ dysfunction during an

individuals’ critical illness.

The PIM2 (Baghurst et al., 2008; Eulmesekian et al., 2007; Inwald et al., 2009; Shann

et al., 1997; Slater et al., 2002; Thukral et al., 2006; Wolfer et al., 2007) is a

regression model that uses admission data to predict intensive care outcomes for

children. The score is designed to be generated using physiological and patient data

available within the first hour of the patients’ admission, to generate an overall risk-

score. Within this study, the PIM2 is being used to describe mortality risk, and

therefore critical illness of the patient groups.

Clinical Pulmonary Infection Score (CPIS)

The Clinical Pulmonary Infection Score (CPIS) (A'Court et al., 1993; Pugin,

Auckenthaler, Miller et al., 1991)(see appendix D) has been commonly used to

measure pneumonia (McClure et al., 2009; Sakaquicki et al., 2008; Singh et al.,

1999), and VAP (Aydogdu & Gursel, 2008; Munro, Grap, Elswick et al., 2006; Pugin,

Auckenthaler, Lew et al., 1991; Sakaquicki et al., 2008), in research. The clinical

diagnosis combines body temperature, white blood cell counts, appearance of tracheal

secretions, oxygenation requirements, infiltrates on chest x-ray, and cultures of

tracheal aspirate to give a cumulative score. Within this study, the CPIS has been

included to examine the link between pneumonia, measured as CPIS, and pathogenic

colonisation of oropharyngeal flora and poor oral health of critically ill children.

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3. 7.4 Data extraction tool

In order to describe the various influences on oral health during critical illness,

information was collected by the principal investigator and summarised using a data

extraction tool (see appendix E & F). Demographic data, information regarding the

participants’ critical illness, oral hygiene care practices and PICU therapies were

obtained from CareVue - a clinical information system. The incidence of HAI was

collected, using the previously defined diagnostic criteria (Horan et al., 2008) with

laboratory data available on AusLab® - an electronic database. Diagnostic samples

for HAI, such as tracheal aspirates and blood, were only obtained when clinically

indicated. The researchers were not involved in the decision-making regarding the

acquiring of diagnostic samples for HAI. Diagnostic samples were processed using

standard microbiological methods and techniques at the Queensland Health Pathology

Services Laboratory.

3. 8 DATA MANAGEMENT

Data were entered regularly throughout the study into the Statistical Package for

Social Sciences (SPSS) program, version 14 (SPSS, Chicago, IL). In order to

minimise potential data entry error, the same person entered the data. To check for

accuracy of data entry, verification for each item on the OAS, oropharyngeal

colonisation, and PIM2 calculations were conducted throughout the study. The

principal investigator was responsible for all data entry. All data collected were kept

in a locked filing cabinet accessible only to the research team, or kept under password

if stored electronically. All data will be maintained and kept for a period of five years

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following the completion of the study. After this time it will be destroyed as per RCH

ethics policy.

3. 9 DATA ANALYSIS

Statistical methods were chosen to answer the previously defined research questions,

within the confines of an observational cohort design, and are defined below.

Statistical analysis was performed using SPSS version 14.0 (SPSS, Chicago, IL).

Statistical significance was set at p≤0.05.

Research Question One:

What is the status of oral health in critically ill children during admission to a PICU?

Descriptive statistics were used to describe oral health using the OAS and

oropharyngeal colonisation. Descriptive statistics were also used describe the

frequency and type of oral hygiene provided, demographic information and the main

clinical characteristics of the participants including age, length of PICU stay,

admission source, primary diagnosis, dentate status, and critical illness severity.

Counts and percentages were calculated for categorical variables, means and standard

deviations (SD) for normally distributed continuous variables and medians and

minimum and maximum values for abnormally distributed continuous variables.

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Research Question Two:

How does the oral health of critically ill children change during their admission to

PICU?

A time series analyses allowed participants to be grouped according to PICU length of

stay in two day intervals (group A <48 hours; group B 48-96 hours; group C 96-144

hours; group D 144-192 hours; group E >192 hours). Categorical and continuous

values for oropharyngeal colonisation and OAS were then described over length of

time in PICU within these interval groups and the sample as a whole.

Research Question Three:

How is the oral health of critically ill children affected by patient characteristics or

PICU therapies?

Oral health, as described by the OAS and oropharyngeal colonisation, was examined

for relationships with multiple patient characteristics and PICU therapies using an

Analysis of Variance (ANOVA). The main analysis was undertaken using data

collected on day two of the participants’ admission to PICU for two reasons: a) to

analyse data that were a result of PICU condition and care (≥48 hours) in comparison

to the oral health of participants on admission, and b) after day two the sample size

reduced quickly due to discharge from PICU or death. A separate analysis was

undertaken to describe the effect the source of admission to PICU had on

oropharyngeal colonisation on the day of admission to PICU.

The ANOVA was used to examine the influence of the independent variables on the

variation of results in the dependent variables (Bhopal, 2008). Different types of

ANOVAs were used depending on the characteristics of the dependent and

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independent variables. Oropharyngeal colonisation was again categorised into ‘nil

flora’, ‘commensal flora’ or ‘pathogenic flora’ as per previous definitions. The OAS

was analysed as a continuous variable and divided into a categorical variable: a score

less than five - no dysfunction; six to ten - moderate dysfunction; greater than or equal

to 11 - severe dysfunction. The data were first checked for normality of distribution to

determine whether parametric or nonparametric statistical tests of variance would be

used. The different ANOVA methods used for the dependent and independent

variables are explained in Table 3.3.

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Table 3.3

Statistical tests for dependent and independent variables

Dependent variables Independent variables Statistical tests

OAS

Oropharyngeal

colonisation (OPC)

Critical illness scores

PIM2

PELOD

Age

Continuous OAS

Spearman’s rho

Categorical OAS & OPC

Kruskal Wallis

OAS

Oropharyngeal

colonisation

ETT present

Dentate status

Primary diagnosis

Oncological condition

Neutropenia

Clinical Pulmonary Infection

Score (CPIS)

Antibiotic therapy & oral anti-

fungal therapy -oropharyngeal

colonisation only

Continuous OAS

Mann-Whitney (2

independents)

Kruskal Wallis (3 or more

independents)

Categorical OAS & OPC

Fishers exact test

Oropharyngeal

colonisation (Day 0)

Admission source Fishers exact test

Research Question Four:

What is the relationship between dysfunctional oral health in critically ill children and

PICU-related HAI?

The data were first checked for normality of distribution to determine whether

parametric or nonparametric statistical tests would be used. The descriptive statistics

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surrounding the clinical characteristics of the participants who developed PICU-

related HAI were summarised using frequency count, percentage, median, minimum

and maximum values. Non-parametric tests of significance - Kruskal, Wallis and

Fishers exact test - were undertaken to compare the demographic, clinical and oral

health characteristics between the two groups (those who developed PICU-related

HAI and those who did not). Cases of HAI and the corresponding oropharyngeal

colonisation results were outlined in a table format.

3.9 ETHICAL CONSIDERATIONS

Ethical approval to conduct the study was obtained from the Royal Children’s

Hospital, Brisbane and the Queensland University of Technology Human Research

Ethics Committees (see appendices G & H). The key elements of the ethical

considerations were informed consent, risk management and confidentiality and

security.

3.9.1 Informed consent

Informed consent for participation was obtained by the principal investigator or

trained PICU personnel. As the population studied were critically ill children, consent

for participation was gained from the child’s parents or legal guardians. The

participants and parents/guardians were provided with oral and written information

about the study and written consent was obtained for each participant prior to

oropharyngeal sampling (see appendix I & J). If the potential participant was greater

than 12 years of age, conscious, and could speak, read and write English, a youth

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assent form was completed (see appendix K). Patients were not eligible for

recruitment if they had no parents or legal guardians present, were under the care of

Child and Family Services, or if the parents or guardians were unable to speak, read

or write English. Methodologically, approach for inclusion in the study was necessary

within 12 hours of PICU admission, however tact was used when choosing the time to

recruit, depending on the clinical condition of the child and the emotional state of the

parent or guardian.

Information was provided verbally and in written form. The information cover

sheet outlined that: 1) participation in the study is voluntary; 2) subjects are free

to withdraw before or during the study without comment or penalty; and 3)

subjects will not be prejudiced as a result of their participation. In addition,

parents, guardians and participants (where applicable) were made aware of the

purpose, nature and risks/benefits of the research. Parent/guardian and youth

assent information sheets and consent forms are shown in appendices 8 and 9.

3.9.2 Risk management procedures

There were no known risks associated with subjects participating in this study, as no

new therapeutic interventions were used and assessments were reasonably non-

invasive. As mentioned previously, consent to participate in the study was entirely

voluntary and participants were free to withdraw from the study at any time without

penalty. As the researcher is a senior nurse on the unit, participants may have thought

that the decision whether or not to participate in the study may threaten provision of

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their future care. However, during the consenting process, participants were informed

that participation or non-participation would not change the care that their child

received in the PICU or the RCH. Nurses were encouraged to group oropharyngeal

swabs within the normal process of care, in order to minimise the disturbance of the

children. The anticipated benefits of participation were the early detection of oral

infections and notification of severe dysfunction to the Children’s Oral Health Service

located in the RCH.

3.9.3 Confidentiality and security

The confidentiality and anonymity of all participants and family members was

assured throughout the study. Coding mechanisms were applied to the data extraction

tool and information collected was not disclosed to anyone other than members of the

research team. No child or family members were identifiable within the final report or

subsequent publications.

All data collected were kept in a locked filing cabinet accessible only to the research

team, or kept under password if stored electronically. All data will be maintained and

kept for a period of five years following the completion of the study and after this

time destroyed, as per RCH ethics protocol.

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Chapter 4 - RESULTS

4.1 INTRODUCTION

This chapter presents the results of the Critically ill Children’s Oral Health (CCOH)

study describing the oral health of critically ill children. The findings of the data

analysis, the characteristics of the study participants, and the data related to each

research question are presented.

4.2 CHARACTERISTICS OF PARTICIPANTS

Participants were recruited to the CCOH study between the 2nd of March 2008 and the

10th of December 2008. Within that period there were 414 admissions to the PICU at

the RCH and all were screened for potential study recruitment. The participants were

recruited following the previously explained inclusion/exclusion criteria. The sample

tree below (see Figure 1), depicts the recruitment of participants process. A total of 46

participants were recruited to the study.

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Figure 1. Participant recruitment sample tree

The demographic characteristics of the CCOH study participants are presented in

Table 4.1. The participants had a wide variety of age, length of PICU stay, dentate

status, primary diagnosis, severity of critical illness and admission sources. In order

to estimate the study’s generalisability, comparisons were made between the CCOH

study population and information made available by the Australia and New Zealand

Paediatric Intensive Care Registry (ANZPICR) (2008) (Alexander et al., 2008).

414 admissions to RCH PICU

300 length of PICU stay < 48 hours

31 not recruited within 12 hours of admission

13 parents/care-givers not present within 12 hours

12 previously participated in study

6 under the care of child and family services

4 parents/care-givers unable to understand English

Informed consent

0 refused

46 participants

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Table 4.1

Demographic characteristics and comparisons of CCOH study participants (n=46) and Australia and New Zealand Paediatric Intensive Care Registry (ANZPICR)

Demographics CCOH f ANZPICR

Age (months) Median

Minimum

Maximum

11.5

0.1

168

24

0.1

348

Length of PICU stay (hours)

Median

Minimum

Maximum

107.5

21

977

28.1

4

>4320

Dentate status Non-dentate 22 47.8% N/A

Dentate 24 52.2%

Participants receiving mechanical ventilation 35 76.0% 54.7%

Non-survivors of PICU 3 6.5% 2.9%

Primary Diagnosis Trauma 4 8.7% 7.3%

Respiratory failure 13 28.3% 22.7%

Post-operative 8 17.4% 24.3%

Neurology 4 8.7% 7.6%

Haematology/ Oncology 7 15.2% N/A

Sepsis 5 10.9% N/A

Other (liver etc) 5 10.9% 14.8%

Cardiovascular 0 0% 23.3%

Admission source Hospital ward 5 10.9% 19.1%

Hospital department of emergency medicine

9 19.9% 16.1%

Outside retrieval 17 32.6% 21.2%

Operating Theatre 15 37.0% 41.3%

PIM2 Median 1.79 1.08

Minimum

Maximum

0.23

31.58 0.02

99.59

PELOD (day 2)

Median 1.00 N/A

Minimum

Maximum

0.00

61.00

Pneumonia (day 2) 8 17.4% N/A

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4.3 DATA ANALYSIS

Checks were conducted to reveal outliers on demographic data - age, length of

Paediatric Intensive Care Unit (PICU) stay, and for scores - the Oral Assessment

Scale (OAS), the Paediatric Index of Mortality (PIM2), the Pediatric Logistic Organ

Dysfunction Score (PELOD) and the Clinical Pulmonary Infection Score (CPIS).

Any discrepancies identified were checked and corrected where necessary.

The data cleaning process identified missing data within the oropharyngeal

colonisation results. Of the 46 study participants, seven (15.2%) did not have

oropharyngeal colonisation sampling completed on one of the required days within

their stay (two participants did not have swabs completed within 12 hours of

admission, seven on day two, four on day four, and one on day six or eight) The

demographics of the participants who had missing values are summarised in Table

4.2. As the missing values are widely spread among the participants’ demographic

groups and range, all available results were included in the final analyses.

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Table 4.2

Summary demographic characteristics of participants with missing oropharyngeal colonisation results (n=7)

Age

(months)

Length of stay

(hours)

Dentate status Primary diagnosis

Median 56 Median 112 Dentate 4 (57.1%) Trauma 1 (14.3%)

Min. 1.5 Min. 109 Non-dentate

3 (42.9%) Neurology 1 (14.3%)

Max. 120 Max. 528 Respiratory failure

3 (42.9%)

Post-operative 1 (14.3%)

Haemotology/ Oncology

1 (14.3%)

Prior to undertaking the statistical analysis, standardisation of the OAS was necessary

to allow direct comparison between the non-dentate and dentate groups. One of the

characteristics of the OAS was assessment of the participants’ teeth, which had an

effect on the total score participants were able to achieve. There were two techniques

available for standardisation: increasing the non-dentate score by one; and factoring

the non-dentate scores by 15 (total available score for dentate group) divided by 12

(total available score for non-dentate group). Previous studies have utilised both

techniques (Gibson & Nelson, 2000; Jiggins & Talbot, 1999), and analyses showed

there were no significant differences in the median and mean results using the two

different methods. Following the rule of parsimony, the simpler method, increasing

the non-dentate score by one, was used for further analysis.

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Oropharyngeal colonisation was categorised into ‘nil flora’, ‘commensal flora’ or

‘pathogenic flora’ as per previous definitions, and analysed as a categorical variable.

The OAS was analysed as a continuous and categorical variable: a score equal to five

indicated no dysfunction; six to 10 indicated moderate dysfunction; greater than or

equal to 11 indicated severe dysfunction.

Checks for normality in distribution were performed on the continuous data. The

OAS, PIM2, PELOD, age and length of stay were positively skewed and three

standard deviations above and below the means did not approximate the minimum

and maximum values. Therefore medians, minimum and maximum values were

utilised for descriptive statistics and non-parametric analysis was undertaken. CPIS

had a normal distribution, however was dichotomised into a categorical variable

(Pneumonia: Yes / No) as per previous definitions.

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4.4 RESULTS OF RESEARCH QUESTIONS

4.4.1 Research Question One - What is the status of oral health in critically ill

children during admission to a PICU?

Within the study, no participants had severe oral dysfunction during their critical

illness, 32 (62.6%) had moderate oral dysfunction and 14 (37.4%) had no oral

dysfunction during the course of their critical illness. Twenty-two participants

(47.8%) had moderate oral dysfunction within 12 hours of their admission to PICU;

and excluding the day of admission, 21 participants (53.8%) had oral dysfunction

during their critical illness.

Nineteen participants (41.3%) had pathogenic oropharyngeal colonisation during their

critical illness. Ten participants (21.7%) had pathogenic oropharyngeal colonisation

within 12 hours of admission to PICU; and excluding day of admission, 15

participants (32.6%) had pathogenic oropharyngeal colonisation during their critical

illness. Half of the participants (n=23; 50.0%) had absent oropharyngeal flora during

their critical illness.

One hundred and fifty-two oropharyngeal swabs were taken during the course of the

study. Table 4.3 summarises the frequency of commensal, pathogenic and

combinations of oropharyngeal flora isolated.

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Table 4.3

Frequency of commensal, pathogenic and combinations of oropharyngeal flora isolated

Commensal flora (n=152) Frequency Percentage

Alpha-haemolytic streptococcus

Coagulase-negative staphylococcus

Non-haemolytic streptococcus

Neisseria sp.

Corynebacterium spp.

65

49

22

19

8

42.76%

32.34%

14.47%

12.50%

5.26%

Pathogenic flora (n=65)

Candida sp.

Staphylococcus aureus

Haemophilus influenzae

Enterococcus sp.

Pseudomonas aeruginosa

Escherichia coli

Acinetobacter sp.

Stenotrophomonas maltophilia

Klebsiella pneumoniae

Enterobacter cloacae

Serratia marcescens

30

11

6

3

3

2

2

2

2

2

2

46.15%

16.92%

9.23%

4.61%

4.61%

3.08%

3.08%

3.08%

3.08%

3.08%

3.08%

Combinations of flora (n=152)

Nil

Commensal only

Pathogenic & commensal

Pathogenic only

45

50

35

22

29.60%

32.89%

23.03%

14.47%

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The most common commensal bacteria isolated from the oropharynx of critically ill

children during this study were the alpha-haemolytic streptococcus (42.76%), with a

wide range of other species colonising less frequently. Candida sp. were the most

common pathogenic organisms to colonise the oropharynx (46.15%), with

Staphylococcus aureus present frequently (16.92%) and a range of gram positive and

gram negative bacteria less frequently. Some participants were colonised with several

pathogenic and/or commensal bacteria at the one time. Commensal colonisation is

most common (32.89%), however an absence of oropharyngeal flora is frequent

(29.60%) and colonisation with both pathogenic and commensal flora is possible

(23.03%).

The oral hygiene care that the participants received during the course of their critical

illness varied widely, as summarised in Table 4.4. The table shows the most frequent

oral cleansing solution used on day two of the participants admission to PICU was

water (77.50%), the most frequent oral cleansing implement used was a foam swab

(62.50%), and the most common frequency of the provision of oral hygiene was every

six hours (40.00%).

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Table 4.4:

Oral hygiene received by participants

Oral cleansing solution used (day two) Frequency Percentage

Nil

Water

Chlorhexidine mouthwash

Toothpaste

Sodium bicarbonate mouthwash

5

31

1

2

1

12.50%

77.50%

2.50%

5.00%

2.50%

Oral cleansing implement used (day two)

Nil

Foam swab

Cotton swab

Toothbrush

5

28

4

3

12.50%

62.50%

10.00%

7.50%

Frequency of oral hygiene (day two)

Nil

Every 4 hours

Every 6 hours

Every 12 hours

Once daily

5

9

16

7

3

12.50%

22.50%

40.00%

17.50%

7.50%

Received oral or systemic antifungal therapy

during PICU admission

6 13.04%

Dentate patients who had their teeth brushed

within 48 hours of PICU admission

2 8.33%

Participants who received oral care using a

cotton swab during PICU admission

16 34.78%

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4.4.2 Research Question Two - How does the oral health of critically ill children

change during their admission to PICU?

In order to examine the change of oral health of the participant’s critical illness and

admission to PICU, two analyses were undertaken. Firstly, the participants were

divided into groups using PICU length of stay to delineate (group A <48 hours; group

B 48-96 hours; group C 97-144 hours; group D 145-192 hours; group E >192 hours).

Table 4.5 presents colonisation results and median and categorical Oral Assessment

Scores over two day intervals in PICU. There was neither upward nor downward

trend in the incidence of pathogenic colonisation or oral dysfunction, nor a change in

median OAS over increasing length of stay in PICU.

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a Frequency and percentage. b Median, minimum and maximum value.

Table 4.5 Colonisation and median and categorical OAS over two day intervals in PICU for subgroups

Colonisation:a Categorical OAS:a

Subgroup Day Nil Commensal Pathogen Normal Moderate Severe Median OAS b

A (n= 9)

<48 hours

0 1 (11%) 6 (55%) 2 (22%) 5 (56%) 4(44%) 0 5.0 (5-8)

B (n = 12) 0 3 (25%) 6 (50%) 3 (25%) 6 (50%) 6 (50%) 0 5.0 (5-9)

48-96 hours 2 1 (11%) 6 (66%) 2 (22%) 7 (58 %) 5 (42%) 0 5.0 (5-8)

C (n=11) 0 5 (50%) 5 (50%) 0 7 (64%) 4 (37%) 0 5.0 (5-8)

97-144 hours

2 6 (55%) 3 (33%) 1 (11%) 8 (73 %) 3 (27%) 0 5.0 (5-8)

4 2 (17%) 2 (33%) 3 (50%) 7 (64%) 4 (36%) 0 5.0 (5-8)

D (n=5) 0 2 (40%) 3 (60%) 0 2 (40%) 3 (60%) 0 6.0 (6-8)

145-192 hours

2 2 (40%) 0 3 (60%) 3 (60%) 2 (40%) 0 5.0 (5-8)

4 1 (20%) 2 (40%) 2 (40%) 5 (100%) 0 0 5.0 (5-5)

6 1 (50%) 1 (50%) 0 3 (60%) 2 (40%) 0 5.0 (5-6)

E (n=10) 0 0 4 (45%) 5 (55%) 4 (40%) 6 (60%) 0 6.0 (5-7)

>192 hours 2 0 4 (57%) 3 (43%) 7 (70%) 3 (30%) 0 5.0 (5-6)

4 3 (33%) 1 (11%) 5 (55%) 5 (50%) 5 (50%) 0 5.5 (5-10)

6 5 (55%) 1 (11%) 4 (45%) 3 (30%) 7 (70%) 0 6.0 (5-10)

8 3 (33%) 3 (33%) 4 (45%) 8 (80%) 2 (20%) 0 5.0 (5-9)

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The second analysis was undertaken using the sample as a whole, rather than subgroups.

Figure 2 presents the colonisation percentages over two day intervals in PICU for the

entire group.

Figure 2. Colonisation percentages over two day intervals

Figure three displays the median OAS for the entire group over two day intervals.

4.5

5

5.5

6

Day 0 Day 2 Day 4 Day 6 Day 8

Days in PICU

Med

ian O

AS

Median OAS

Figure 3. Median OAS over two day intervals

0%

10%

20%

30%

40%

50%

60%

Day 0 Day 2 Day 4 Day 6 Day 8

Days in PICU

Nil Flora Commensal FloraPathogen

Per

cen

tage

of

Col

onis

atio

n

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Figure four displays OAS percentages for the whole group over two day intervals.

Figure 4. Categorical OAS percentages over two day intervals

These figures support previous results showing no upward or downward trend in oral

health over length of stay in PICU.

4.4.3 Research Question Three – How is the oral health of critically ill children affected

by patient characteristics or PICU therapies?

The main analysis undertaken used data collected on day two of the participants’

admission to PICU to examine the effect of patient characteristics and PICU therapies on

the participants’ oropharyngeal colonisation and OAS. The OAS was analysed as both a

continuous (range - five to 15) and categorical (normal, moderate dysfunction or severe

dysfunction) variable, the oropharyngeal colonisation only as a categorical variable.

Oropharyngeal flora was analysed primarily with the categories of nil, commensal,

0%10%20%30%40%50%60%70%80%90%

Day 0 Day 2 Day 4 Day 6 Day 8

Days in PICU

Normal Moderate Severe dysfunction

OA

S P

erce

nta

ge

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pathogenic, but some analysis was performed using the dichotomy of – pathogenic;

yes/no.

The patient characteristics examined were critical illness scores (PIM2 and PELOD), age,

dentate status, primary diagnosis, oncological condition, neutropenia and presence of

pneumonia as measured by CPIS. The PICU therapies examined were presence of an oral

or nasal endotracheal tube (ETT), antibiotic therapy and oral anti-fungal therapy. A

secondary analysis was undertaken to describe the effect admission source to PICU had

on oropharyngeal colonisation on day zero of PICU stay. As previously described, a

variety of statistical methods were utilised: Spearman’s rho for continuous dependent and

independent variables; Mann-Whitney and Kruskal-Wallis for mixed categorical and

continuous variables; and Fishers exact test for categorical dependent and independent

variables. Only one independent variable had a statistically significant effect on the OAS.

The critical illness measurement PELOD was significantly associated with oropharyngeal

colonisation with x2=6.166 with df =2, and a p-value of 0.046.

4.4.4 Research Question Four - What is the relationship between dysfunctional oral

health in critically ill children and PICU-related healthcare-associated infections (HAI)?

Eight (17.4%) participants developed a PICU-related HAI during their critical illness.

Compared with the 38 participants free of HAI, these eight participants had an increased

median length of stay in the PICU (p=0.002), a higher median OAS on day two of

admission to PICU (p=0.245) indicating moderate dysfunction, and a higher critical

illness score (PELOD: p=0.072). The demographic and clinical characteristics of the

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population are summarised in Table 4.6. The types of infection, isolated strains and

results of oropharyngeal flora sampling are given in Table 4.7.

Table 4.6.

Demographics and clinical characteristics of population developing HAI during PICU admission (n=8)

Admission source n (f)

RCH ward 2 (25.0%)

RCH department of emergency medicine 0

Outside RCH retrieval 2 (25.0%)

Operating Theatre 4 (50.0%)

Primary Diagnosis

Trauma 2 (25.0%)

Respiratory failure 1 (12.5%)

Post-operative 1 (12.5%)

Neurology 1 (12.5%)

Haematology / Oncology 2 (25.0%)

Sepsis 1 (12.5%)

Other (liver etc) 0

Participants receiving mechanical ventilation 7 (87.5%)

Non-survivors of PICU 1 (12.5%)

Dentate status

Dentate 2 (25.0%)

Non- Dentate 6 (75.0%)

Min Max Median

Age (months) 2.0 168.0 25.0

Length of PICU stay (hours) 107.0a 972.0 259.5

OAS (on day 2) 5.0 8.0 5.5

PIM2 0.57 6.16 2.91

PELOD (day 2) 0 21 10.5b ap=0.002 b p=0.072

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Table 4.7.

Oropharyngeal sampling results and PICU-related HAI

Day No.

Oropharyngeal colonisation Type of HAI Pathogen in HAI Day of HAI

0

Commensal flora & Haemophilus influenzae

Pneumonia

(ETT aspirate) Haemophilus

influenzae

2

2 Commensal flora & Acinetobacter baumannii

4 Commensal flora & Acinetobacter baumannii

0 Commensal flora &

Escherichia coli

Pneumonia (ETT aspirate)

Pseudomonas aeruginosa

2

2 Commensal flora & Candida sp.

4 Candida albicans

6 Pseudomonas aeruginosa & Candida albicans

8 Commensal flora

0

Commensal flora &

Haemophilus influenzae

Pneumonia (ETT aspirate)

Candida sp.

2

2-6 Commensal flora & Candida sp.

8

Commensal flora, Haemophilus influenzae & Candida sp.

Pneumonia (ETT aspirate)

Staphylococcus aureus & Haemophilus influenzae

8

10 Not done

12 Commensal flora & Candida albicans

14-18 Commensal flora

20 Klebsiella pneumoniae, Enterobacter cloacae & Candida albicans

22-24 Commensal flora

26 Klebsiella pneumoniae, Enterobacter cloacae & commensal flora

28 Not done

30-32 Commensal flora

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Day No.

Oropharyngeal colonisation Type of HAI Pathogen in HAI Day of HAI

34-36 Nil flora

38 Commensal flora

0 Nil Blood-stream infection (Blood culture)

Enterococcus faecalis 4

2-4 Commensal flora & Staphylococcus aureus

0-6 Commensal flora Bacteraemia

(Blood Culture) Escherichia coli 6

0

Staphylococcus aureus & commensal flora

Pneumonia (ETT aspirate)

Candida sp. 10

2 Not done

4

Staphylococcus aureus, Candida sp. & commensal flora

6-18 Candida sp.

20 Nil

0-4 Not Done Pneumonia

(ETT aspirate)

Candida sp. 14

6-8 Nil

10 Commensal flora & Candida sp.

12-14 Nil

16 Candida albicans

18-22 Nil

0-4 Candida albicans Blood-stream infection (Blood culture)

Stenotrophomonas Maltophilia

18

6-10 Nil

12-14 Pseudomonas aeruginosa

16

18 Stenotrophomonas maltophilia Nil

20 Stenotrophomonas maltophilia

22-24 Serratia marcescens & commensal flora

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During their PICU stay, two participants acquired a blood-stream infection or bacteraemia

(Enterococcus faecal is (n=1) and Escherichia coli (n=1)) without concurrent oropharyngeal

colonisation. One participant developed pneumonia (Pseudomonas aeruginosa) on day two

of admission to PICU, and the same organism was isolated in their oropharyngeal flora four

days later.

In the five remaining participants (four with pneumonia, one with bacteraemia), the

pathogens found in their blood or endo-tracheal tube (ETT) aspirates were also isolated from

oropharyngeal sampling - simultaneously in one participant, and before any other sampled

site of colonisation in the remaining four participants. One participant, who was admitted

with a pneumonia caused by Haemophilus influenzae, developed two PICU-related HAI’s

during their critical illness, one of which was associated with oropharyngeal colonisation

prior to its development.

4.5 SUMMARY

Forty-six participants were recruited to the CCOH study between the 2nd of March 2008 and

the 10th of December 2008. Greater than half (n=32; 62.6%) of critically ill children in the

CCOH study had oral dysfunction during their critical illness, as measured by the OAS.

Forty-one percent of critically ill children in the study had pathogenic oropharyngeal

colonisation during their critical illness. The oral hygiene care that the participants received

during the course of their critical illness varied widely.

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There was neither upward nor downward trend in the incidence of pathogenic colonisation or

oral dysfunction, nor a change in median OAS over increasing length of stay in PICU. After

examining multiple patient characteristics and PICU therapies for influence on oral health,

only the critical illness measurement PELOD was significantly associated with oropharyngeal

colonisation.

Eight (17.4%) participants developed a PICU-related HAI during their critical illness. In five

participants (four with pneumonia, one with bacteraemia), the pathogens found in their blood

or ETT aspirates were also isolated from oropharyngeal sampling - simultaneously in one

participant, and before any other sampled site of colonisation in the remaining four

participants.

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CHAPTER 5 - DISCUSSION

5.1 INTRODUCTION

It is inevitable that some children in the general population will become critically

unwell and require intensive treatment in a Paediatric Intensive Care Unit (PICU).

Whilst critically ill, some children may have characteristics and receive PICU therapies

which put them at an increased risk for poor oral health and pathogenic oropharyngeal

colonisation. The oral cavity is fragile, and because of this, may easily become

dysfunctional and harbour pathogenic microorganisms. Pathogenic microorganisms,

such as Staphylococcus aureus, can cause severe systemic illnesses including

pneumonia and blood-stream infection. Worryingly, PICU nurses are ill-informed

regarding best practice for oral hygiene and its significance for their patients.

The primary goal of the Critically ill Children’s Oral Health (CCOH) study was to

describe the oral health of critically ill children. In addition, the study sought to examine

the influence of time in PICU, patient characteristics and PICU therapies on oral health,

and explore the relationship between poor oral health and PICU-acquired healthcare-

associated infections (HAI). Current knowledge regarding this area is limited and

heavily reliant upon extrapolation of adult data. Given the importance placed on

maintaining oral health in the adult critical care population by international institutions

such as the Centers for Disease Control and Prevention (CDC), the current limitations

of the paediatric research need to be addressed.

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5.2 KEY FINDINGS

5.2.1 What is the status of oral health in critically ill children during admission to a

PICU?

The CCOH study aimed to describe the status of oral health in critically ill children

through use of the Oral Assessment Scale (OAS) and microbial colonisation in the

oropharynx. Greater than half (n=32; 62.6%) of critically ill children in the CCOH study

had oral dysfunction during their critical illness, as measured by the OAS. Oral

dysfunction manifested in various ways - development of ulcers, dental plaque, cavities,

cracked lips, decreased salivary flow, or generalised inflammation and infection. These

oral dysfunctions represent a breakdown in the local and systemic health of these

critically ill children. Decreased salivary flow, or xerostomia, causes a change in the

immunological defences within the oral cavity facilitating adhesion of pathogenic

organisms. Cracked lips, generalised infection and ulcers, display a breakdown in the

primary defence mechanism of the mouth, allowing infiltration of these pathogenic

organisms into the wider circulatory system. A build up of dental plaque has been

shown in adult populations to be a reservoir for respiratory pathogens, such as

Staphylococcus aureus and Pseudomonas aeruginosa (Fourrier et al., 1998;

Scannapieco et al., 1992). It could be concluded from this that oral dysfunction via each

of these mechanisms potentially contributes to the systemic health of children during

critical illness. Oral dysfunction, as an indicator of poor oral health, has been shown to

be equally prevalent in adult critical care studies (Munro, Grap, Elswick et al., 2006;

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Scannapieco et al., 1992). Evidence-based oral hygiene practices need to be instituted to

improve the oral health of critically ill children.

Oral dysfunction, as quantified by the OAS, may be symptomatic of underlying

microflora changes. Forty-one percent of critically ill children in the study had

pathogenic oropharyngeal colonisation during their critical illness, which reinforces

previous work by Thorburn (2009). The most common pathogenic oropharyngeal

colonisation was with Candida sp., with similar prevalence seen in Singhi et al’s (2008)

descriptive study examining generalised Candidaemia in the PICU. Candida sp. are

frequently present in the oropharynx of healthy children (Hannula et al., 1999) as part of

commensal flora, however within the CCOH study the Candida sp. were considered

pathogenic when prevalent in high numbers (≥106 colony forming units (cfu) per litre)

indicating opportunistic colonisation. Candida sp. frequently are opportunistic

pathogens of blood-stream and respiratory infections in critically ill patients and those

with compromised immune status (Singhi et al., 2008). Over the last decade there has

been an increase in the incidence of opportunistic Candida sp. bloodstream and

respiratory infections in hospitals (Singhi et al., 2008), particularly in the critically ill.

Primary colonisation of Candida sp. within the oropharynx facilitates the entry of a

potential systemic pathogen to the respiratory and circulatory system.

In addition to Candida sp., the other potential respiratory and systemic pathogens

colonising the oropharynx of critically ill children during this study included

Staphylococcus aureus, Haemophilus influenzae, Enterococcus sp., and Pseudomonas

aeruginosa in accord with previous adult and paediatric studies (Fourrier et al., 1998;

Garrouste-Orgeas et al., 1997; Rubenstein et al., 1992; Scannapieco et al., 1992;

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Thorburn et al., 2009). Respiratory and systemic pathogens are not usually prominent

members of the oral commensal flora of healthy adults (Scannapieco et al., 1992) or

children (Kononen, 2005). This suggests that the oropharynx of critically ill children

can act as a reservoir for these pathogens which have the potential to cause systemic

infections including pneumonia and blood-stream infections, which are consequently

associated with substantial morbidity and mortality (Chan et al., 2007; D. Jones &

Munro, 2008; Safdar et al., 2005).

Half of the participants (n=23; 50%) within the CCOH study had absent commensal

oropharyngeal flora during their critical illness. The absence of commensal microflora

has previously been described as poor or dysfunctional oral health (Marsh & Percival,

2006), as the unique functions of the microflora are absent. Within the oral cavity this

involves the commencement of the process of digestion and a barrier against

colonisation or overgrowth of potentially pathogenic micro-organisms. Oral hygiene

protocols for critically ill children need to stratify for PICU therapies and patient

characteristics associated with the absence of commensal flora, as well as provide

strategies to support the regeneration of commensal oropharyngeal flora and prevent

opportunistic overgrowth of pathogenic microorganisms.

Within this study, information surrounding oral care practices was collected by audit

and while this may not be completely reflective of actual practice, the nurses caring for

these children demonstrated wide variation in oral hygiene practices. A large proportion

of the critically ill children described in the study had oral dysfunction and the nurses’

practice surrounding choice of instruments, solutions and frequency of oral care was not

informed by patient characteristics or current research. Only 8% of dentate children had

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their teeth brushed within 48 hours of admission to PICU, 12.5% of children received

no oral hygiene on day two of admission to PICU and cotton swabs were used in 35%

of patients. Even though a high proportion of the population had Candida sp. isolated

on their oropharyngeal swabs, only 13% received oral anti-fungal therapy. It would be

difficult to suggest that this nursing practice was informed by evidence, and this may be

reflected in the frequency of oral dysfunction in the critically ill children. Like all

patient management practices, oral health can be best managed through the institution of

evidence-based oral hygiene protocols specific to critically ill children.

5.2.2 How does the oral health of critically ill children change during their admission

to PICU?

Our findings of no change or trend, either positively or negatively, surrounding oral

health over PICU admission within the CCOH study, challenges other studies within

critical care. The previous descriptive study completed by Franklin et al (2000) found a

statistically significant increase in mean plaque scores during PICU stay

(admission=22.5; discharge=25.8; p=0.001) and gingival inflammation (admission=4.1;

discharge=5.5; p=0.006). Fourrier et al (1998), in their descriptive study on adult critical

care, also found a statistically significant increase in dental plaque on patients remaining

ICU for five days or greater (day 0: 1.1 ± 0.7; day 5: 1.6 ± 0.7; p<0.05). Their study also

found the frequency of colonisation by aerobic pathogens increased over length of ICU

stay (day 0: 27%; day 5: 40% and day 0: 31%; day 5: 38%; day 10: 46%) but the

number of participants in each group was too low to reach statistical significance.

Worsening oral health over time spent in PICU has been used to demonstrate the

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ineffectiveness of current oral hygiene practices (Franklin et al., 2000), specifically the

efficacy of foam swabs; this study however, disputes this finding.

The reason for the difference between the CCOH study results to previous adult

(Fourrier et al., 1998) and paediatric (Franklin et al., 2000) studies in critical care may

be due to several factors. Considering the difference in critical care outcomes and the

diversity in baseline oral health components between the adult and paediatric

populations, a variation in study findings could be expected. The study by Franklin et

al., (2000) is the only other study found examining the change in composition of the

oral health of critically ill children over time in PICU. The inclusion criteria in the

CCOH study were broader than in Franklin et al’s., (2000), and included all patients

regardless of dentate status, which is arguably a more accurate reflection of critically ill

children. The oral assessments completed in the CCOH study were carried out by bed-

side clinicians, in comparison to dental care assistants in the study by Franklin et al.,

(2000). However the OAS has been shown to have sound reliability and validity in

multiple studies (Andersson et al., 1999; Barnason et al., 1998; Eilers et al., 1988;

Ferozali et al., 2007; Holmes & Mountain, 1993; Jiggins & Talbot, 1999) using bed-side

clinicians. Given the study by Franklin et al., (2000) is a singular study, and the

inclusion criteria and assessment methods utilised in the two studies were substantially

different, variation in results should be expected.

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5.2.3 How is the oral health of critically ill children affected by patient characteristics

or PICU therapies?

Literature suggests that PICU therapies (e.g. intubation (Jiggins & Talbot, 1999),

antibiotics (Jiggins & Talbot, 1999; Sixou et al., 1996)), and patient characteristics

including age (Kononen, 2000), severity of critical illness (Rubenstein et al., 1992;

Thorburn et al., 2009), admission source (Toltzis, Hoyen, Spinner-Block, Salvator, &

Rice, 1999), neutropaenia (Sixou et al., 1996) and admission diagnosis (Sixou et al.,

1996; Thorburn et al., 2009)), would have a relationship with the oral health of critically

ill children. Unexpectedly, the majority of patient characteristics and PICU therapies

examined in this study had little or no relationship with the status of oral health of

participants. An increase in the severity of critical illness, as measured by the Pediatric

Logistic Organ Dysfunction Score (PELOD), demonstrated a statistically significant

positive association (p=0.046) with pathogenic or absent oropharyngeal flora, in

comparison to commensal flora. It has been established in adult studies that severe

illness alters the oropharyngeal flora (Fourrier et al., 1998; Scannapieco et al., 1992;

Thorburn et al., 2009). The CCOH study findings correlate with the study by

Rubenstein et al. (Rubenstein et al., 1992), which found that PICU patients who were

colonised orally with pathogenic microflora such as Candida sp. had higher levels of

critical illness (Pediatric Risk of Mortality: 12.9 ± 2.8 vs. 4.9 ± 1.0; p=0.01).

PELOD (Leteurtre et al., 1999) measures the severity of critical illness by quantifying

the severity of multiple organ dysfunction. The link between organ dysfunction and

pathogenic or absent oropharyngeal colonisation is logical when recognising the support

and treatment organ dysfunction often requires within the PICU. Therapies including

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antibiotics, intubation and fluid restriction, all of which have previously been suggested

as possible causes of microbial flora changes within the oral cavity (Kite & Pearson,

1995; Sixou et al., 1996), are instituted to support a child with worsening organ

dysfunction. Jiggins and Talbot (1999) previously developed a ‘risk assessment for oral

disease’ for use in the PICU, and while not validated, it is comprised of therapies used

to support children during organ dysfunction, including ventilation, sedation, dialysis

and diuretics. The development and validation of a risk assessment for poor oral health

in critically ill children would be a valuable addition to an evidence-based oral hygiene

protocol, allowing for stratification of ‘at risk’ children.

Within the CCOH study, critically ill children who were orally intubated did not have a

significantly higher incidence of dysfunctional oral health or pathogenic oropharyngeal

colonisation, in comparison to self-ventilating or nasally intubated patients. This

contrasts previous studies which describe nurses as being ‘uneasy’ or ‘unwilling’ to

provide oral hygiene to patients who were orally intubated as they viewed the risk of

accidental extubation as being too great (Binkley et al., 2004; Fitch et al., 1999; Rello et

al., 2007b). Either this attitude was not active within the RCH study group, or the oral

hygiene practices did not have an effect on the outcome of oral health. An analysis of

the effect of oral hygiene practices on oral health was not within the scope of this study.

Owing to both the variety of oral hygiene practices provided to each participant

throughout their admission to PICU and the size of a master’s thesis, this additional

record was not undertaken. Further research needs to be conducted to explore PICU

nurses’ current knowledge and practice surrounding oral health and oral hygiene.

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As the only patient characteristic to have a relationship with worsening oral health was

severity of critical illness, oral hygiene protocols need to be focussed on increasing

support for children with severe levels of critical illness. Other patient and clinical

characteristics, such as age, dentate status and admission diagnosis, need to be

incorporated into oral hygiene protocols for practical purposes. Protocols need to be

developed to encompass a variety of solutions, instruments and frequency with

stratification for severity of critical illness. To ensure feasibility, the oral hygiene

protocols need to take into consideration the attitudes and knowledge of PICU nurses

surrounding oral health and oral hygiene.

5.2.4 What is the relationship between dysfunctional oral health in critically ill children

and PICU-related healthcare-associated infections (HAI)?

Of the population described by this study, 17.4% (eight) developed a PICU-related HAI

during their critical illness. HAIs are a common, serious problem in critically ill

children and are associated with substantial morbidity and mortality along with

increased attributable costs. Within the CCOH study, in comparison to the participants

who did not develop a PICU-related HAI, this group had higher critical illness scores

(PELOD: p=0.072) and longer length of admission (p=0.002). Notably within the scope

of this study, the participants who developed a PICU-related HAI had a median OAS of

5.5 (5.0-8.0) on day two of admission to PICU, indicating moderate dysfunction, in

comparison to the remaining PICU population having a median OAS of 5.0 (5.0 – 8.0).

While this relationship did not reach statistical significance (p=0.245) and sample size

does not allow further statistical analysis, this trend towards poor oral health in critically

ill children who developed a PICU-related HAI may indicate a potential relationship

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between the development of HAI and poor oral health. Adult critical care studies have

confirmed that poor oral health (Munro, Grap, Elswick et al., 2006), and pathogenic

oropharyngeal colonisation (Abele-Horn et al., 1997; Garrouste-Orgeas et al., 1997;

Pugin, Auckenthaler, Lew et al., 1991), increases the risk of HAI, such as pneumonia.

Further research regarding this area in paediatrics is required before causal relationships

can be suggested.

Not all participants in the CCOH study who had pathogenic oropharyngeal colonisation

during their admission to PICU developed a PICU-related HAI. However, of the eight

participants who did develop a PICU-related HAI, six (75%) participants (five

pneumonias, one blood-stream infection) had the causative pathogens isolated from

oropharyngeal sampling previously or simultaneously. While these results are limited

by small sample size, they echo previous findings in adult critical care by Fourrier et al

(1998) and Munro et al. (2006). The CCOH study results suggest that the oropharynx

of critically ill children could be a reservoir of potential systemic bacterial and fungal

pathogens. PICU-related HAI as a result of translocation of pathogens from the

oropharynx to the respiratory and cardiovascular systems are physiologically plausible.

Oral hygiene treatment strategies should be directed towards reducing the prevalence of

pathogenic oropharyngeal colonisation and improving oral health.

The most common oropharyngeal pathogen to be associated with a consecutive PICU-

related HAI within the study was Candida sp., with three participants being colonised in

their oropharynx prior to developing clinically evident pneumonia, caused by Candida

sp. Critically ill patients and those with compromised immune status are prime targets

for opportunistic Candida infection (Singhi et al., 2008). The known predisposing

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conditions for increased colonisation by Candida sp. include prematurity, antibiotic

therapy, central venous catheter, use of antacids, immunosuppression, immuno-

deficiency and malnutrition (Singhi et al., 2008), all of which are frequently present or

occur during critical illness in childhood. The other oropharyngeal pathogens associated

with a consecutive PICU-related HAI within the CCOH study were Haemophilus

influenzae, which later was the causative agent for pneumonia, and Stenotrophomonas

maltophilia, which later was the causative agent for a blood-stream infection. Whether

the oropharynx was the first site of colonisation for the pathogens, or whether the

oropharyngeal colonisation was coincidental or causative, has not been established by

this study due to limitations with sample size and design, however it does suggest that

further research in this area needs to be completed.

While traditional definitions of ‘pathogenic’ microorganisms have been used in the this

study, in the immunocompromised patient a significant proportion of bacteraemias have

been associated with opportunistic commensal oral bacteria including Streptococci sp.

(Lucas, Beighton, Roberts, & Challacombe, 1997). Oral Streptococci, particularly the

Streptococci oralis group of the viridans Streptococci, are frequently isolated from

blood cultures of febrile neutropaenic patients and the incidence of septicaemia caused

by commensal bacteria in this clinical sub-group is increasing (Lucas et al., 1997).

However, the majority of critically ill children have a symbiotic relationship with their

commensal oropharyngeal flora, therefore patients who are at risk of developing

opportunistic infections from commensal flora need to be identified and oral hygiene

strategies tailored to facilitate this.

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5.3 STRENGTHS AND LIMITATIONS OF THE STUDY

Limitations of the CCOH study include its observational design and low sample size

(n=46). Consequently, the study lacks the ability to generate powered correlations

(Bhopal, 2008; Friis & Sellers, 2009) and is limited in its generalisability. However, the

study was intended to be exploratory. Considering the paucity of current literature

surrounding the oral health of critically ill children, the CCOH study has broadened the

body of knowledge available on the subject. Although the study design did not allow the

comparison of results to healthy controls, the significance of the results is not

diminished. Of the 46 participants, greater than half (n=32) had moderate oral

dysfunction during their critical illness, which has the potential to significantly affect

systemic health, no matter what the comparative prevalence in healthy populations.

One measurement of the status of oral health within the study was accomplished

through the OAS. A potential weakness of the study may be the effectiveness of the

OAS to adequately measure oral health, however substantial evidence exists to attest to

its historical reliability and validity (Andersson et al., 1999; Barnason et al., 1998;

Eilers et al., 1988; Ferozali et al., 2007; Holmes & Mountain, 1993; Jiggins & Talbot,

1999). Due to the OAS primarily objective design and given that other authors have

previously completed inter-rater reliability testing (Andersson et al., 1999; Barnason et

al., 1998; Eilers et al., 1988; Ferozali et al., 2007; Holmes & Mountain, 1993; Jiggins &

Talbot, 1999) and recent authors (Gibson & Nelson, 2000; Ross & Crumpler, 2007)

have not repeated testing, inter-rater reliability testing was not undertaken prior to this

study. While the OAS was completed by multiple assessors, education surrounding its

use is extensive and multi-faceted. Previous researchers (Munro, Grap, Jablonski et al.,

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2006) have advocated the measurement of oral health via dental plaque and salivary

volume, however these measurements are elements of the OAS, so were not repeated.

Information on the sub-groups of the pathogens isolated on oropharyngeal swabs was

limited as semi-quantitative analysis was undertaken, which did not sub-classify all

bacterial and fungal types. The bacterial and fungal types chosen for analysis were

informed by previous research in adults and paediatrics and advised by a panel of

experts consisting of senior microbiologists and clinicians. Bed-side clinicians obtained

the oropharyngeal swabs rather than a single investigator, however nurses were trained

individually by the principal investigator and information was placed at the bedside

regarding the saliva sampling protocol.

While limitations are present in the study, it is the first of its kind to fully describe the

oral health of critically ill children and provides background information for the

development of further studies. In comparison to previous studies, oral health was

systematically described using a validated assessment scale in combination with

microbiological analysis. The CCOH study was successful in examining the effect of

length of time in PICU, PICU therapies and patient characteristics on oral health.

A further strength of the CCOH study, in comparison to previous research in the area, is

the wide inclusion criteria. The study participants are an accurate representation of

critically ill children, including all patients regardless of their age, dentate status or

ventilatory support. However, the study did not include children with a primary

diagnosis of a cardiac condition as the RCH PICU does not have a cardiac service. The

participants were heterogeneous which, while challenging when undertaking

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correlations, is necessary to adequately and completely describe a complicated

population. Future development of oral hygiene protocols will also need to encompass

this heterogeneity.

5.4 STUDY FINDINGS AND THEIR IMPLICTIONS FOR CLINICAL PRACTICE

The study results covered in this chapter, their clinical significance and supporting

literature, lead to the following conclusions:

Oral health is frequently dysfunctional during critical illness in childhood at the

RCH PICU. A large percentage of RCH critically ill children show signs of poor

oral health including inadequate salivary flow, dental plaque and ulcers.

Potential systemic pathogens are frequently isolated from the oropharynx of

critically ill children including Candida sp., Staphylococcus aureus,

Haemophilus influenzae, Enterococcus sp., and Pseudomonas aeruginosa.

Critically ill children in the PICU at the RCH frequently have absent

oropharyngeal flora, which is indicative of poor oral health.

PICU nurses working at the RCH conduct a wide variation in oral hygiene

practices some of which are not supported by current research.

In contrast to previous research (Fourrier et al., 1998; Franklin et al., 2000), the

oral health of critically ill children admitted to the RCH PICU did not worsen

over length of stay in PICU.

The severity of critical illness has a significant positive relationship with

pathogenic and absent colonisation of the oropharynx. Oral hygiene practices

should be more aggressive for children with high levels of critical illness.

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A large percentage of PICU-related healthcare-associated infections involve

preceding or simultaneous colonisation of the oropharynx by the causative

pathogen.

While further study is required to determine the full merit of these conclusions, given

their potential impact upon clinical practice, further investigation appears warranted.

5.5 SUMMARY

Given the prevalence of dysfunctional oral health during childhood critical illness in the

RCH PICU population, and combined with the potential systemic consequences,

evidence based paediatric oral hygiene practices should be developed. These orl hygiene

practices should be researched to ensure effectiveness in improving the oral health of

critically ill children and be developed to take into considerations risk factors for

developing poor oral health.

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CHAPTER 6 - CONCLUSION

6.1 Introduction

Within adult critical care research and practice, clinicians have acknowledged the

profound effect oral health has on systemic health (Abele-Horn et al., 1997; A. Berry &

Davidson, 2006; Binkley et al., 2004; Brennan et al., 2004; Chan et al., 2007; Cutler,

2005; Dennesen et al., 2003; Ewig et al., 1999; Fitch et al., 1999; Fourrier et al., 1998;

Garrouste-Orgeas et al., 1997; D. Jones & Munro, 2008; McNeill, 2000; Munro & Grap,

2004; Munro, Grap, Elswick et al., 2006). Despite this, little is known surrounding the

oral health of critically ill children and its relationship with systemic health. The

purpose of the Critically ill Children’s Oral Health (CCOH) study was to describe the

state of oral health during childhood critical illness, examine the relationship between

poor oral health and a variety of clinical characteristics, and explore the relationship

between poor oral health and systemic infections. A prospective observational cohort

study was undertaken at a single tertiary-referral Paediatric Intensive Care Unit (PICU).

The status of oral health was measured using the Oral Assessment Scale (OAS) (Eilers

et al., 1988) and culturing of the oropharyngeal flora. Information was also collected

concerning the use of supportive PICU therapies, clinical characteristics of the children

and the occurrence of PICU related healthcare-associated infections (HAI).

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6.2 RESEARCH QUESTION CONCLUSIONS

Oral health has the potential to influence systemic health during critical illness in

childhood. This study has demonstrated that oral health is frequently dysfunctional and

the oropharynx frequently harbours potential systemic pathogens during childhood

critical illness. Considering this, it is worrying that PICU nurses working at the Royal

Children’s Hospital (RCH) had variable oral hygiene practices, some of which are not

supported by current research. The only clinical characteristic which had a relationship

with dysfunctional oral health described in this study, was severity of critical illness.

This had a significant positive relationship with pathogenic or absent colonisation of the

oropharynx. In contrast to previous research (Fourrier et al., 1998; Franklin et al., 2000),

the oral health of critically ill children admitted to the RCH PICU did not worsen over

length of stay in PICU. In addition to the physiological plausibility of translocation of

oropharyngeal flora to the blood stream and respiratory tract, this study found a large

percentage of PICU-related HAI involved preceding or simultaneous colonisation of the

oropharynx by the causative pathogen. While further study is required to determine the

full merit of the conclusions generated in the CCOH study, given their potential impact

upon clinical practice, further investigation would appear warranted.

6.3 RECOMMENDATIONS AND FURTHER RESEARCH

The prevalence of poor oral health during childhood critical illness in the RCH PICU

population, combined with potential systemic consequences supports the development

of evidence-based paediatric oral hygiene practices. The development of these

evidence-based practices should include well-controlled clinical trials incorporating all

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aspects of oral care interventions including solution, instruments and frequency. These

interventions could then be summarised in a protocol to help create useful and

appropriate clinical practices. Preferably, the protocol should involve regular oral

assessment utilising a validated oral assessment scale, be tiered by severity of critical

illness and be governed by the practical elements of dentate status, conscious level,

intubation status and developmental age.

There is currently minimal research exploring the relationship between dysfunctional

oral health and deteriorating systemic health within paediatric critical illness.

Specifically the link between pathogenic oropharyngeal colonisation and ventilator

associated pneumonia (VAP) should be further examined. Considering the mortality,

morbidity and economic consequences of VAP, this needs to be addressed.

There is little information available surrounding current PICU oral hygiene nursing

practice. While elements of oral hygiene practices were collected as part of the CCOH

study, this is indicative of a small sample of nurses from a single Australian PICU.

Additionally, no information is available concerning the attitudes, beliefs, training and

knowledge of health care workers within PICU surrounding oral health. Current theory

surrounding oral hygiene provision is based on extrapolation from adult literature

(Binkley et al., 2004; Fitch et al., 1999; Rello et al., 2007a). A multi-centre survey

should be undertaken to ascertain the current state of oral health practices and the

attitudes, beliefs, training and knowledge of health care workers within PICU.

In summary, given the findings of the CCOH study, several recommendations can be

made:

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Evidence based oral hygiene practices and protocols need to be instituted to

improve the oral health of critically ill children.

Oral hygiene practices and protocols should be directed towards reducing the

prevalence of pathogenic oropharyngeal colonisation and improving oral health.

Oral hygiene practices and protocols need encompass the heterogeneity of the

PICU population.

Oral hygiene practices and protocols need to be focussed on increasing support

with severe levels of critical illness.

The development and validation of a risk assessment for poor oral health in

critically ill children would be a valuable addition to an evidence-based oral

hygiene protocol, allowing for stratification of ‘at risk’ children.

Oral hygiene protocols need to take into consideration the attitudes and

knowledge of PICU nurses surrounding oral health and oral hygiene.

Further research needs to be conducted to explore PICU nurses’ current

knowledge and practice surrounding oral health and oral hygiene.

Further research needs to be conducted surrounding the link between poor oral

health as pathogenic oropharyngeal colonisation and the development of HAI.

Patients who are at risk of developing opportunistic infections from commensal

flora need to be identified and oral hygiene strategies tailored to facilitate this.

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6.4 CONCLUSION

The CCOH study has established that oral health is often clinically and

microbiologically dysfunctional during critical illness in childhood. Future research

should focus on the development of evidence-based oral hygiene practices for

integration into PICU clinical practice. While the CCOH study has contributed to the

body of knowledge available surrounding the oral health of the critically ill child,

further research needs to be completed to ascertain the relationship between oral health

and HAI in this population.

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Leteurtre, S., Martinot, A., Duhamel, A., Gauven, F., Grandbastien, B., Nam, V., et al. (1999). Development of a pediatric multiple organ dysfunction score: use of two strategies. Medical Decision Making, 19(4), 399-410. Leteurtre, S., Martinot, A., Duhamel, A., Proulx, F., Grandbastien, B., Cotting, J., et al. (2003). Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. The Lancet, 362(9379), 192-197. Lucas, V., Beighton, D., Roberts, G., & Challacombe, S. (1997). Changes in the oral streptococcal flora of children undergoing allogeneic bone marrow transplantation. Journal of Infection, 35, 135-141. Marsh, P., & Percival, R. (2006). The oral microflora - friend or foe? Can we decide? International Dental Journal, 56(4 (Supplement)). McClure, J., Cooke, R., Lal, P., Pickles, D., Majjid, S., Grant, C., et al. (2009). Outcome of late-onset hospital-acquired pneumonia related to causative organism. Journal of Hospital Infections, Jan 20, Epub ahead of print. McNeill, H. (2000). Biting back at poor oral hygiene. Intensive and Critical Care Nursing, 16, 367-372. Munro, C., & Grap, M. (2004). Oral health and care in the intensive care unit: state of the science. American Journal of Critical Care, 13(1), 25-33. Munro, C., Grap, M., Elswick, R., McKinney, J., Sessler, C., & Hummel, R. (2006). Oral health status and development of ventilator-associated pneumonia: a descriptive study. American Journal of Critical Care, 15(5), 453-460. Munro, C., Grap, M., Jablonski, R., & Boyle, A. (2006). Oral health measurement in nursing research: state of the science. Biological Research for Nursing, 8(1), 35-42. Napenas, J., Brennan, M., Bahrani-Mougeot, F., Fox, P., & Lockhart, P. (2007). Relationship between mucositis and changes in oral microflora during cancer chemotherapy. Oral Surgery Oral Medicine Oral Pathology Oral Radiology And Endodontics 103, 48-59. O'Reilly, M. (2003). Oral care of the critically ill: a review of literature and guidelines for practice. Australian Critical Care, 16(3), 101-110. Passos, J., & Brand, L. (1966). Effects of agents used for oral hygiene. Nursing Research, 15(3), 196-202. Paulsson, G., Wardh, I., Andersson, P., & Ohrn, K. (2008). Comparison of oral assessments between nursing staff and patients on medical wards. European journal of cancer care, 17, 49-55. Pugin, J., Auckenthaler, R., Lew, D., & Suter, P. (1991). Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. JAMA, 265(20), 2704-2710. Pugin, J., Auckenthaler, R., Miller, N., Janssens, J., Lew, P., & Suter, P. (1991). Diagnosis of ventilator-associate pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic 'blind' bronchoalveolar lavage fluid. American Review of Respiratory Disorders, 143, 1121-1129. Rello, J., Koulenti, D., Blot, S., Sierra, R., Diaz, E., De Waele, J., et al. (2007a). Oral care practices in intensive care units: a survey of 59 European ICUs. Intensive Care Medicine, 33(6), 1066-1070. Rello, J., Koulenti, D., Blot, S., Sierra, R., Diaz, E., De Waele, J., et al. (2007b). Oral care practices in intensive care units: a survey of 59 European ICUs. Intensive Care Medicine, 33, 1066-1070. Roberts, M. (1998). Antibiotic resistance in oral / respiratory bacteria. Critical reviews in oral biology and medicine, 9(4), 522-540.

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Ross, A., & Crumpler, J. (2007). The impact of an evidence-based practice education program on the role of oral care in the prevention of ventilator-associated pneumonia. Intensive and Critical Care Nursing, 23, 132-136. Rubenstein, J., Kabat, K., Shulman, S., & Yogev, R. (1992). Bacterial and fungal colonization of endotracheal tubes in children: a prospective study. Critical Care Medicine, 20(11), 1544-1549. Safdar, N. M. D. M. S., Dezfulian, C. M. D., Collard, H. R. M. D., & Saint, S. M. D. M. P. H. (2005). Clinical and economic consequences of ventilator-associated pneumonia: A systematic review. Critical Care Medicine, 33(10), 2184-2193. Sakaquicki, M., Shime, N., S., F., & Hashimoto, S. (2008). Current problems in the diagnosis and treatment of hospital-acquired methicillin-resistant Staphylococcus aureus pneumonia. Journal of Anaesthesia, 22(2), 125-130. Santanae, M., Leite, H., de Carvalho, W., & Lopes, E. (2009). Hypophosphatemia in critically ill children: Prevalence and associated risk factors. Pediatric Critical Care Medicine, Jan 30, Epub ahead of print. Scannapieco, F., Stewart, E., & Mylotte, J. (1992). Colonization of dental plaque by respiratory pathogens in medical intensive care patients. Critical Care Medicine, 20(6), 740-745. Schleder, B. (2003). Taking charge of ventilator-associated pneumonia. Nursing Management, 34(8), 27-33. Shann, F., Pearson, G., Slater, A., & Wilkinson, K. (1997). Paediatric index of mortality (PIM): a mortality prediction model for children in intensive care. Intensive Care Medicine, 23, 201-207. Singh, N., Gayowski, T., Wagener, M., & Marino, I. (1999). Pulmonary infiltrates in liver transplant recipients in the intensive care unit. Transplantation, 67(8), 1138-1144. Singhi, A., Raman Rao, D., & Chakrabarti, A. (2008). Candida colonization and candidemia in a pediatric intensive care unit. Pediatric Critical Care Medicine, 9(1), 91-95. Sixou, J., Medeiros-Batista, O., & Bonnaure-Mallet, M. (1996). Modifications of the microflora of the oral cavity arising during immunosuppressive chemotherapy. Oral Oncology: European journal of cancer, 32B(5), 306-310. Sixou, J., Medeiros-Batista, O., Ganddemer, V., & Bonnaure-Mallet, M. (1998). The effect of chemotherapy on the supragingival plaque of pediatric cancer patients. Oral Oncology, 34, 476-483. Slater, A., Shann, F., & Pearson, G. (2002). PIM2: a revised version of the Paediatric Index of Mortality. Neonatal and Pediatric Intensive Care, 29, 278-285. Somerville, R. (1999). Oral care in the intensive care setting: a case study. Nursing in Critical Care, 4(1), 7-13. Stiefel, K., Damron, S., Sowers, N., & Velez, L. (2000). Improving oral hygiene for the seriously ill patient: implementing research-based practice. Medsurg Nursing, 9(1), 40-43. Suljagic, V., Cobeljic, M., Jankovic, S., Mirovic, V., Markovic-Denic, L., Romic, P., et al. (2005). Nosocomial bloodstream infections in ICU and non-ICU patients. American Journal of Infection Control (AJIC), 33(6), 333-340. Sullivan, P., Juszczak, E., Bachlet, A., Lambert, B., Vernon-Roberts, A., Grant, H., et al. (2005). Gastrostomy tube feeding in children with cerebral palsy: a prospective, longitudinal study. Developmental medical and childhood neurology, 47(2), 77-85.

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Tablan, O., Anderson, L., Besser, R., Bridges, C., & Hajjeh, R. (2003). Guidelines for preventing health-care associated pneumonia. Altanta: Centers for Disease Control and Prevention. Thorburn, K., Jardine, M., Taylor, B., Reilly, N., Sarginson, R., & van Saene, H. (2009). Antibiotic resistant bacteria and infection in children with cerebral palsy requiring mechanical ventilation. Pediatric Critical Care Medicine, 10(2), 222-226. Thukral, A., Kohli, U., Lodha, R., Kabra, S., & Kabra, N. (2007). Validation of the PELOD score for multiple organ dysfunction in children. Indian Pediatrics, 44(9), 683-686. Thukral, A., Lodha, R., Irshad, M., & Arora, N. (2006). Performance of Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality (PIM) and PIM2 in a pediatric intensive care unit in a developing country. Pediatric Critical Care Medicine, 7(4), 356-361. Toltzis, P., Hoyen, C., Spinner-Block, S., Salvator, A., & Rice, L. (1999). Factors that predict preexisting colonization with antibiotic-resistant gram negative bacilli in patients admitted to a Pediatric Intensive Care Unit. Pediatrics, 103(4), 719-723. Tombes, M., & Galluci, B. (1993). The effects of hydrogen peroxide rinces on the normal oral mucosa. Nursing Research, 42(6), 332-337. Turton, P. (2008). Ventilator-associated pneumonia in paediatric intensive care: a literature review. Nursing in Critical Care, 13(5), 241-248. Veldman, A., Trautschold, T., Weiss, K., Fischer, D., & Bauer, K. (2006). Characteristics and outcome of unplanned extubation in ventilated preterm and term newborns on a neonatal intensive care unit. Paediatric Anaesthesia, 16(9), 968-973. White, R. (2000). Nurse assessment of oral health: a review of practice and education. British Journal of Nursing, 9(5), 260-266. Wolfer, A., Silvani, P., Musicco, M., & Salvo, I. (2007). Pediatric Index of Mortality 2 score in Italy: a multicenter, prospective, observational study. Intensive Care Medicine, 33(8), 1407-1413. Yung, M., Wilkins, B., Norton, L., & Slater, A. (2008). Glucose control, organ failure and mortality in pediatric intensive care. Pediatric Critical Care Medicine, 9(2), 147-152. Zolldann, D., Thiex, R., Waitschies, B., Lutticken, R., & Lemmen, S. (2005). Periodic surveillance of nosocomial infections in a neurosurgery Intensive Care Unit. Infection, 33(3), 115-121.

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APPENDICES

Appendix A

Oral Assessment Scale (OAS)

Lips – feel, observe 1 = Smooth, pink, moist

2 = Dry or cracked

3 = Ulceration or bleeding

Tongue – feel, observe 1 = Smooth, pink, moist

2 = Coated / shiny appearance, increased/decreased redness

3 = Thick and large, inflamed, blistered or ulcered

Saliva - observe 1 = Thin, watery and plentiful

2 = Thick or decreased

3 = Ropy or absent

Gingiva/oral mucosa – observe 1 = Smooth, pink, moist

2 = Generally pale, with small amount of reddened areas or ulcers, dry

3 = Bleeding, inflamed, multiple ulcers, very dry and oedematous

Teeth - observe 0 = Non-dentate

1 = Clean, no debris

2 = Plaque/debris in localised area

3 = Plaque/debris generalised, cavities visable

Tool modified from Beck (1979).

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Appendix B

Pediatric Logistic Organ Dysfunction score (PELOD)

0 1 10 20 Neurological * Glasgow Coma Score 12-15 7-11 4-6 3 and Pupillary Reactions Both reactive N/A Both fixed N/A

Cardiovascular † Heart rate (beats/min) < 12 years ≥12 years

≤195 ≤150

N/A N/A

>195 >150

N/A N/A

Systolic Blood pressure (mmHg) <1 month 1 month-1year 1-12 years >12years

<140 <55 <100 <140

N/A N/A N/A N/A

35-65 35-75 45-85 55-95

<35 <35 <45 <55

Renal Creatinine (µmol/L) <7 days 7 days-1 year 1-12 years >12 years

<140 <55 <100 <140

N/A N/A N/A N/A

≥ ≥ ≥ ≥

N/A N/A N/A N/A

Respiratory PaO2 (kPa)/FiO2 ratio >9.3 and N/A ≥ or N/A PaCO2 (kPa) ≤11.7 and N/A >11.7 N/A Mechanical ventilation § No Ventilation Ventilation N/A N/A Haematological White blood cell count (x10 9/L) ≥4.5

and 1.5-4.4 or

<1.5 N/A

Platelets ≥35 <35 N/A N/A Hepatic Aspartate transaminase (IU/L) <950

and ≥950 or

N/A N/A

Prothrombin time ¶ (or INR) >60 (<1.40)

≤60 (≥1.40)

N/A N/A

Note: PaO2=arterial oxygen pressure. FiO2=fraction of inspired oxygen. PaCO2=arterial carbon dioxide pressure. INR=International normalised ratio. *Glasgow Coma Score: use lowest value. If patient is sedated, record estimated GCS before sedation. Assess patient only if known or suspected acute central nervous system disease. Pupillary reactions: non-reactive pupils must be >3mm. Do not assess after iatrogenic pupillary dilatation. †Heart rate and systolic blood pressure: do not assess during crying iatrogenic agitation. § PaO2: use arterial measurement only. ¶ Percentage of activity. PaO2/FiO2 ratio, which cannot be assessed inpatients with intracardiac shunts, is considered as normal in children with cyanotic heart disease. PaCo2 may be measured from arterial, capillary or venous samples. Mechanical ventilation: the use of mask ventilation is not counted as ventilation. Score = 0; no oral dysfunction Score = 1-103; increasing organ dysfunction

Tool modified from Lacroix & Cotting, 2005; Leteurtre et al., 1999; Leteurtre et al., 2003; Santanae et al., 2009; Thukral et al., 2007; Yung et al., 2008.

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Appendix C

Paediatric Index of Mortality 2 (PIM2)

PIM2 Logistic Regression Model (n=20787)

Variables Coefficient 95% CI

Absolute (SBP -120), mmHg 0.01395 0.01054 to 0.01735

Pupils fixed to light (Y/N) 3.0791 2.7712 to 3.3869

100xFiO2 / PaO2, mmHg-1 0.2888 0.2015 to 0.3760

Absolute (base excess) mmol/l 0.1040 0.0919 to 0.1161

Mechanical ventilation (Y/N) 1.3352 1.1188 to 1.5516

Elective admission (Y/N) -0.9282 -1.1795 to -0.6768

Recovery post procedure (Y/N) -1.0244 -1.3235 to -0.7254

Bypass (Y/N) 0.7507 0.3971 to 1.1043

High risk diagnosis (Y/N) 1.6829 1.5185 to 1.8473

Low risk diagnosis (Y/N) -1.5770 -2.0244 to -1.1296

Constant -4.8841 -5.1132 to -4.6549

Note: SBP = Systolic Blood Pressure; mmHg = Millimetres of mercury; FiO2 = Fraction of inspired oxygen; PaO2 = Partial pressure of oxygen; Mmol/l = Millimols per litre Result 0.01 = 1% risk of mortality Result 99.9 = 99% risk of mortality

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Appendix D

Clinical Pulmonary Infection Score (CPIS)

Parameter Value Score

Temperature (Celsius) 36.5 – 38.4 0

28.5 – 39.0 1

<36.0 - >39.0 2

White Blood Cells (mm-3) 4.0 – 11.0 0

11.0 – 17.0 1

>17.0 2

Secretions Nil 0

+ 1

++ 2

FiO2 / PaO2 (ratio in kPa) >33 0

<33 2

(unless ARDS, then 0)

Chest radiograph infiltrates clear 0

patchy 1

localised 2

Culture of tracheal aspirate No or < 1+ pathogenic bacteria cultured

0

>1+ pathogenic bacteria cultured

1

Note: FiO2 = Fraction of inspired oxygen; PaO2 = Partial pressure of oxygen; kPa = Kilopascals; ARDS = Acute Respiratory Distress Syndrome

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Appendix E

Data Extraction Tool Participant _______________ UR No______________ Database No______________ Primary Dx_______________ Survivor YES/NO Dentate / Non-Dentate Age_______ Admission Source ________________ Adm Date/Time ____________ D/C Date/Time_____________

OAS PIM 2

PELOD CPIS Antibiotics

Y/N

Intubated

Y/N

PO Anti-fungal

Y/N

Neutro-penia

Y/N

Oral Hygiene (Freq, solution, implement)

Day 0

Day 2

Day 4

Day 6

Day 8

Day 10

Day12

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Appendix F

Oropharyngeal Colonisation & Healthcare-Associated Infections

Participant _______________

Oropharyngeal

PICU Related Healthcare Associated Infection

DAY 0:

DAY 2:

DAY 4:

DAY 6:

DAY 8:

DAY 10:

DAY 12:

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Appendix G

Ethical approval from Royal Children’s Hospital, Brisbane HREC

ROYAL CHILDREN'S HOSPITAL & HEALTH SERVICE DISTRJCT ETHICS COMMIITEE

Professor John Peam (Chair) 3365 5323 Mo Amanda Smith (Co-ordinator) 36369167

Ms Amanda UIlman Paediatric ICU Royal Children's Hospital & Health Service District Herston QLD 4029

Dear Ms lJIlman,

Queensland Government

Queensland Health

Lc:vel3. RCH Foundation Building Royal Children's Hospital

Herstoo QLD 4029 Australia Telephone (07) 3636 9167 Facsimile (07) 3365 54SS

23" Oclober 2007

Oropharyngeal flora in criticaUy ill children: changing compositioD during time spent in the

PICU.

Many thanks for your letter of the 28th September with responses to queries raised by the Committee in relation to the above project.

This was tabled at our meeting on the 22nd October and the Committee are happy to give their approval for this important work.

Please do Dot hesitate to contact me should you have any queries.

With kindest regards,

Professor John Peam Chair Royal Children's Hospital and Health Service District Ethics Committee

Cc: Ethics Commitlee files (professor John Peam) Members of the Ethics Committee

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Appendix H

Ethical approval from the Queensland University of Technology HREC

University Human Research Ethics Committee

HUMAN ETHICS APPROVAL CERTIFICATE

NHMRC Registered Committee Number EC00171

Dear Mrs Amanda Ullman

A UHREC should clearly communicate its decisions about a research proposal to the researcher and the final decision to approve or reject a proposal should be communicated to the researcher in wrrting. This Approval Certificate serves as your written nolioo that the proposal has met the requirements of Ihe Nalional Slatemenl on Research involving Human Participation and has been approved on that basis. You are therefore authorized to commence activities as oumned in your proposal application, subject to any specific and standard conditions detailed in this document

Within this Approvat Certificate are:

• Project Details • Participant Details • Conditions of Approval (Specific and Standard)

Researchers should report to the UHREC, via the Research Ethics Officer. events that might affect continued ethical acceptability of the project. including, but not limited to:

(a) serious or unexpected adverse effects on participants; and (b) proposed significant changes in the conduct, the participant profile or the risks of the proposed research,

Further information regarding your ongoing obligations regarding human based research can be found yia the Research Ethics website hllp:lAw.w.research.quLedu.au/ethics/ or by contacting the Research Ethics Coordinator on 07 3138 2340 or [email protected]

If any details wlthm thiS Approval

thiS cerllficate J I lficale are incorrect please advise Research Ethics within 10 days of receipt of

Research Eth,cs Orrrcer =±�ti: 1&;;;-___________ _

(on behalf of the Chairperson U C)

I Projlu::t Detaits

Category of Approval : Approved by other HREC

Approved Until: 28/0412011

Approval Number: 0800000252

Date

Project Title: Oral health of critically itl children: changing composition during time spent in the PICU

Project Chief Invest igator: Mr5 Amanda Ullman

Other Project Slaff/Students: Or Peter lewis , Prof Glenn Gardner , Ms Debbie long, Ms Desley Hom , Or M3rk Coulth3rd

Experiment Summary: Investigate whether the composition of the oropharyngeal nora of critically ill children undergoes similar changes to that seen in the adult ICU and paediatric Oflcology.

I Participant Det ails

PartiCipants: Approximately 90 aged between 1 day and 15 years

locationis of the Work: PaediatriC Intensive Care Unit, Royal Children's Hospitat, Herston

RM Report No. E801 VersiO!1 2

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109

University Human Research Ethi�s commi:!e HUMAN ETHICS APPROVAL CERTIFICATE

NHMRC Registered Committee Number EC00171

I Conditic>ns of Approval

Specific Conditions of Approval:

No special conditions placed on approval by the UHREC. Standard conditions apply.

Standard Conditions of Approval:

The University's standard conditions of approval require the research team to:

1 Conduct the project in accordance with University policy. NHMRC I AVCC guidelines and regulations, and the provisions of any relevant Slate I Territory or Commonwealth regulations or legislation;

2. Respond 10 the requests and instructions of the University Human Research Ethics Committee (UHREC);

3. Advise the Research Ethics Officer immedialely if any complaints are made, or expressions of concern are raised. in relation to the project;

4. Suspend or modify the project if the risks to participants are found to be disproportionate to the benefits. and immediately advise the Research Ethics Officer of this action;

5. Stop any involvement of any participant if continuation of the research may be harmful to that person. and immediately advise the Research Ethics Officer of this action;

6. Advise the Research Ethics Officer of any unforeseen development or events that might affect the continued ethical acceptability of the project;

7. Report on the progress of the approved project at least annualty, or at intervals determined by the Committee;

8. (Where the research is publicly or privately funded) publish the results of the project is such a way to permit scrutiny and contribute to public knowledge; and

9. Ensure that the results of the research are made available to the participants.

Modifying your Ethical C learance:

The University has an expedited mechanism for the approval of minor modifications to an ethical clearance (this includes changes to the research team, subject pool, lesting instruments, etc). In practice this mechanism enables researchers to conduct a number of projects under the same ethical clearance.

Any proposed modification to the project or variation to the ethical clearance must be reported immediately to the Committee (via the Research Ethics Officer), and cannot be implemenled until the Chief Investigator has been notified of the Committee's approval for the change f variation.

Requests for changes f variations should be made in writing 10 the Research Ethics Officer. Minor changes (changes to the subject pool, the use of an additional instrument, etc) will be assessed on a case by case basis and interim approval may be granted subject to ratification at the subsequent meeting of the Committee.

It generally takes 7 -14 days to process and notify the Chief Investigator of the outcome of a request for a minor change I variation.

Major changes to your project must also be made in writing and will be considered by the UHREC. Depending upon the nature of your request. you may be asked to submit a new application form for your project.

Audits:

All active ethical clearances are subject to random audit by the UHREC, whiCh will include the review of the signed consent forms for participants, whether any modifications f variations to the project have been approved, and the data storage arrangements.

End 01 Oocumenl

RM Report No. E801 Version 2

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Appendix I

Parent / guardian information and consent forms

ROYAL CHILDREN’S HOSPITAL AND HEALTH SERVICE DISTRICT PARENT/GUARDIAN INFORMATION SHEET

Project Title: Oropharyngeal flora in critically ill children: changing composition during time spent in the PICU. Investigators: Ms Amanda Ullman (PICU Registered Nurse) Ms Debbie Long (PICU Nurse Researcher)

Ms Desley Horn (PICU Nurse Unit Manager) Contact Person:Ms Amanda Ullman PICU Registered Nurse Level 2, Surgical Building Royal Children's Hospital Ph: 07 3636 7957 Introduction You are invited to participate in a study that aims to assess whether the composition of the flora in the oral cavity of critically ill children changes during the course of their admission to the Paediatric Intensive Care Unit. We are sorry that your child is sick in Intensive Care and realise that this is a very stressful time for you. Thank you for taking the time to consider allowing your child to be part of this study. Background Oral health has a profound effect on general health. It is estimated that upwards of 500 species of bacteria normally inhabit the mouth. These bacteria have an important role in providing protection from illness-causing bacteria and organisms such as Staphylococcus aureus. However we think that during illness the oral cavity of critically ill children can change to become a source of infection, which could easily be transmitted to both the blood stream and the respiratory tract. Thorough studies have investigated this subject in adult intensive care and paediatric oncology patients, but no-one has investigated this in critically ill children. We know that children have different ‘normal’ flora (or bacteria) in their mouth before they get sick. The children within the Paediatric Intensive Care often have significant risk factors for developing illness-causing bacteria in the mouth, such as needing a tube to help them breathe or antibiotics.

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As we mentioned previously, bacteria and organisms in the mouth can quickly transmit to both the blood stream and the respiratory tract. In a critically ill child, this can lead to pneumonia, a bloodstream-infection called septicaemia, or a urinary tract infection. These infections are often referred to as nosocomial infections. Nosocomial infections can be life threatening, increase PICU and hospital length of stays and have considerable cost implications related to medications and therapies. We think that the identification and prevention of illness-causing bacteria through a simple task of oral cares can have a significant impact on the lives of critically ill children. The results of this study aim to provide the foundations of further research where evidence based oral care regimes in critically ill children will be evaluated. Description of Research We would like to find out whether the bacteria in the mouths of critically ill children changes during the course of their admission to the Paediatric Intensive Care Unit (PICU). To do this we need to place a cotton-tipped swab in your child’s mouth for approximately thirty seconds, to collect a sample of their saliva. This will be sent to the laboratory to identify the bacteria/organisms that are present. We will take oral swabs on the day that your child is admitted to the PICU, and then every second day, while they are admitted to PICU. The results from these swabs will inform us whether the oral flora has changed from being good, ‘normal’ bacteria, to infection-causing ‘bad’ organisms. Your child would receive our standard treatment for oral hygiene. In addition to standard treatment, every day the nurses would assess the oral cavity for signs of infection or inflammation using an Oral Assessment Scale. If there is evidence of a large amount of inflammation or infection, a referral would be made to the Oral Health Service, within the Royal Children’s Hospital. If your child develops a nosocomial infection during the course of their admission to the PICU, we would then compare the organisms/bacteria found in the mouth with the bacteria/organisms found in the infection. Are there any risks involved? No, there are no risks involved. The oral swabs are minimally invasive and are not painful. Having the swab taken is similar to having a small soft toothbrush gently placed in your mouth. Are there any benefits? Yes, your child’s oral health status will be closely monitored and if their oral health deteriorates, they will be referred to the Oral Health service within the Royal Children’s Hospital for follow up. Withdrawing from the Study Your decision whether or not for your child to participate in this research will not prejudice their future relations with the Royal Children's Hospital and Health Service District. If you decide for your child to participate, you are free to withdraw your consent and to discontinue participation at any time. The decision to withdraw from the study will not affect their routine medical treatment or their relationship with the people treating them.

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Confidentiality This project is being conducted in accordance with National Health and Medical Research Council ethical guidelines. All information will be kept in the strictest confidence in a locked filing cabinet and only the researchers will have access to the information. No information about the project will be published in any form that would allow any individual to be recognised. Auditors, ethics committees and regulatory authorities may access the anonymous data to ensure that the research is being properly conducted and meeting ethical rules and regulations. However, identifying data is not used. Contact If you wish to discuss any aspect of this study please phone Amanda Ullman on (07) 3636 7957. If you have concerns about the conduct of this study please contact the Chair of the Royal Children's Hospital Ethics Committee on (07) 3636 5323 or the Executive Director of Medical Services on (07) 3636 7590. Thank you for your consideration of this project.

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Appendix J

ROYAL CHILDREN'S HOSPITAL AND HEALTH SERVICE DISTRICT PARENT/GUARDIAN CONSENT FORM

PARTICIPANT I have read the above information. I have asked all of my questions and I have gotten answers. I agree to enrol my child in this study. ______________________________________________________________ Signature of Parent or Guardian Date INVESTIGATOR I have fully explained to the parent/guardian ……………………………… the nature and purpose of the research and the procedures to be employed as described above and such risks as are involved in their performance, and I have provided the parent/guardian with a copy of the Parent/Guardian Information Sheet. ______________________________________________________________ Signature of Investigator Date ______________________________________________________________ Print Name Position INDEPENDENT WITNESS I have witnessed the receipt of an Information Sheet by the parent/guardian and the exchanging of information between the investigator and the parent/guardian about the study. ______________________________________________________________ Signature of Witness Date ______________________________________________________________ Print Name Position

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Appendix K

Youth assent information and consent forms

ROYAL CHILDREN'S HOSPITAL AND HEALTH SERVICE DISTRICT CHILD/ADOLESCENT INFORMATION SHEET Project Title: Oropharyngeal flora in critically ill children: changing composition during time spent in the PICU. Investigators: Ms Amanda Ullman (PICU Nurse) Ms Debbie Long (PICU Nurse) Ms Desley Horn (PICU Nurse) Introduction This letter tells you about a project we are doing at the hospital. Your Doctor has told us that you need to stay in the Children’s Intensive Care Unit for the next few days. In your mouth you have hundreds of little good bacteria that help keep your mouth and teeth healthy. We know that when adults and kids with cancer get sick and need to stay in hospital, the bacteria in their mouth goes from being good to bad, which can make them get even sicker. We would like to ask you for your permission to participate in our project to help figure out whether this happens when you stay in the Children’s Intensive Care Unit. What will happen? In the Children’s Intensive Care Unit we have a team of special doctors and nurses looking after you and your family will be able to visit you here. If you decide to participate in our project a nurse will look in your mouth to see if your gums, teeth and tongue are healthy, like when you go to the dentist. Every second day they will put a cotton-tipped swab in the corner of your mouth for about 30 seconds. The swab is like placing a small soft toothbrush in your mouth. We will then send that swab to a scientist’s laboratory that will look at it under a microscope and see if the bacteria in your mouth are good or bad. Risks & Discomfort While you’re in the Children’s Intensive Care Unit the nurses will clean your teeth like normal. The nurse will put the cotton-tipped swab in your mouth which feels bit like a toothbrush. In the children’s intensive care unit we will try to minimise the amount of

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pain or discomfort that you might have. This study will not involve any more pain or discomfort than what you have already discussed with your parents or doctor. Benefits We want to make sure that children staying in intensive care, like you, receive the best possible care. The information that we get from this project will hopefully tell us how we can take care of you better. Withdrawing from the Study Your decision whether or not to participate in this project will not affect the care or treatment that you receive at this hospital. If you decide to participate, you can say no and withdraw your decision and discontinue participation at any time. If you like, you can talk more about this project to your Mum or Dad, or any of the Doctors or Nurses. If you are happy to participate in our project, please tick yes or no at the bottom of the page by your name. Your name will not be in our project, so people who read it will not know who you are. Thank you for helping us understand more about children who are sick in the intensive care unit. Name: ____________________________________ Yes No