Febrile Illness – Emergency Management in Children

Document ID CHQ-GDL-00707 Version no. 2.0 Approval date 23/11/2016

Executive sponsor Executive Director Medical Services Effective date 23/11/2016

Author/custodian Director, Paediatric Emergency Medicine Review date 23/11/2019

Supercedes 1.0

Applicable to All CHQ HHS clinical staff

Authorisation Executive Director Hospital Services

Purpose

This procedure provides clinical practice guidelines to guide clinicians involved in the emergency management of fever in infants and children. It aims to identify those at risk of serious bacterial or other significant illness who need timely treatment, whilst avoiding unnecessary investigations in the majority.

Scope

This procedure applies to all staff involved in the care and management of children who present with fever as their primary complaint. This guideline is not intended to be used for prolonged fever of greater than one week, when a broader differential diagnosis must be considered.

Management of fever in the neutropenic paediatric oncology patient is beyond the scope of this guideline and should be managed according to the specific Oncology Guideline. Sepsis must be considered in every paediatric patient with fever (Refer to Sepsis- Recognition and Early Emergency Management in Children Guideline)

Procedure

Fever is one of the most common reasons for paediatric presentations to emergency services and provides diagnostic and management challenges to clinical staff. Infection remains the leading cause of death in children under the age of 5 years.

Fever definition and measurement

A practical definition of fever is temperature ≥38°C measured at home or in hospital.

In children under the age of 4 weeks body temperature should be measured with an electronic thermometer in the

axilla. In children aged 4 weeks to 5 years body temperature should be measured by an electronic thermometer in

the axilla, chemical dot thermometer in the axilla or infra-red tympanic thermometer. Forehead chemical

CHQ-GDL-00707 – Febrile Illness

- 2 -

-

thermometers are unreliable and should not be used by healthcare professionals. A parent’s touch has been shown

to have high sensitivity and low specificity for discovering a fever6 however parental concern should be considered

valid and taken seriously.

Pathophysiology of fever 1,9

Fever is a physiological response most often caused by an infective process when exogenous pyrogens (e.g.

bacterial toxins, antibody-antigen complexes) induce endogenous pyrogens (e.g. TNFα, IL-B1, IL-6 and interferons)

resulting in an elevated body temperature. The thermoregulatory centre then raises and maintains the body

temperature to the new set point. This may negatively stress some children with pre-existing cardiac, respiratory or

neurological diseases, and gives most children a degree of malaise. However fever is thought to be a generally

beneficial adaptive response that promotes the immune response and inhibits the invading pathogen, potentially

reducing the duration of certain infections.

Epidemiology of fever

Febrile illnesses comprise approximately 20% of paediatric emergency presentations.10,11 Most (80%) have a readily identifiable source of the fever.12 Of the remaining 20%, most will have a self-limiting viral infection, however a small proportion will have a serious bacterial infection (SBI) or be febrile from conditions such as Kawasaki disease, vaccination reactions, arthritis or connective tissue disorders, malignancies, drug fever, or inflammatory bowel disease. Post vaccination fever usually begins within 24 hours of immunisation and lasts for 2-3 days. Teething does not cause fever > 38.5 oC

In a large Australian children’s hospital study, 7.5% of febrile children <5 years old had a SBI; 3.4% had a urinary tract

infection (UTI); 3.4% pneumonia; 0.4% bacteraemia and 0.1% meningitis.13 Pyrexia of unknown origin (PUO)14 is any

fever lasting 10 - 21 days without cause identified on history, examination and basic investigations.

Serious bacterial infection (SBI)

SBI includes UTI, pneumonia, meningitis, bacteraemia, osteomyelitis, septic arthritis, skin and soft tissue infection or

bacterial enteritis; though only the first four are likely to present in an occult fashion with significant frequency. In

infants less than three months of age, hypothermia or temperature instability can be signs of SBI or other serious

illness.

UTI

This is a relatively common infection in febrile children <5 years. In the 1st year of life, 6.5% girls and 3.3% boys

(1.2% of circumcised vs. 8% of uncircumcised males) will have a UTI. In the 2nd year, the rates become 8.1% girls

and 1.9% boys15 and decrease thereafter. UTI is also the most common SBI causing fever without localising signs,

at approximately 5%.16

Pneumonia

About 3 - 4% all febrile children under 5 years13 and approximately 5% with fever without localising signs have a

pneumonia, though most will be viral in origin. Increasing pneumococcal immunisation may continue to decrease the

incidence of bacterial pneumonia due to the commonest bacterial agent, Streptococcus pneumoniae.

CHQ-GDL-00707 – Febrile Illness

- 3 -

-

Bacteraemia

The incidence of occult bacteraemia has fallen from over 10% to <0.5%12,18 of febrile children aged three months to

three years. This is largely due to effective immunisation against Haemophilus influenzae type b (HIB) &

Streptococcus pneumoniae. Rates are higher (approximately 2 - 10%) in non and pre-vaccinated children depending

on age. Meningococcaemia occurs in only 0.02% of young febrile infants <2 - 3 months,19,20 but approximately 15%

of these may not appear ill-looking.21 Other common pathogens, particularly in infants < 6 months, include

Salmonella species (which may be associated with diarrhoea) and E. Coli (which may accompany UTI).16

Meningitis

The incidence of meningitis is generally very low,13 but more common in younger infants, who may present with

subtle signs and symptoms.

Assessment

A well-taken history and thorough clinical examination should aim to identify:

a. children who have a focus of infection that may then be investigated and treated , and

b. children for whom no infective focus may be found and who may require further investigations and/or empirical

treatment according to their risk of SBI.

Factors that may assist in risk stratification include:

child’s age

immune status - incomplete immunisations, immune-compromise

signs of toxicity

current or recent use of antibiotics

presence of concerning signs and symptoms (e.g. petechial rash)

Age

Several meta-analyses15,23,24 have shown that febrile young infants <3 months have a high risk of SBI (7-24%). This

risk is greatest in the neonatal period and decreases progressively with increasing age. Young infants are more

likely to present with non-specific features (they lack the hypothalamic and immune system maturity to localise the

infection) and can deteriorate rapidly25. In addition to the pathogens seen in older children, Group B Streptococcus,

E. Coli, Herpes Simplex virus, and Listeria monocytogenes infections are more common in this period. Detecting

other viral infections (e.g. RSV) lowers but does not remove the risk of SBI (7% vs. 12.5% for SBI (mainly UTI) in

one large study.22 More recently a study26 found the incidence for SBI in infants one to three (1 - 3) months

decreased significantly if they had bronchiolitis, however the UTI rate was still 4%. A systematic review27 supported

the use of screening for UTI in bronchiolitic children aged one to three (1-3) months as this was the only SBI with

significant incidence (3.3%).

It is important to remember that babies less than 3 months may not necessarily mount a fever in response to SBI,

and that hypothermia or temperature instability can be signs of SBI.

Children aged three months to three years have a lower risk of SBI than the group under three months, and have

their immunity boosted with vaccinations. Occult bacterial infection is most commonly UTI, pneumonia or

bacteraemia. In this age group, the presence of a recognisable viral syndrome (including bronchiolitis) predicts a

very low incidence of bacteraemia (0.2%).28

CHQ-GDL-00707 – Febrile Illness

- 4 -

-

Older children (>3 years) have mature immune systems, are better able to verbalise and localise symptoms and are

at lower risk of SBI.

Immunisations & Immune status

The risk of occult bacteraemia (OB) and SBI has fallen in the last 20 years with the advent of several vaccines, in

particular the Haemophilus influenzae type b (HIB) and pneumococcal (PC) immunisations. Recent studies suggest

that OB rates have fallen to <0.5% in immunised children 3 - 36 months with fever without localising signs on history

or examination .12,18 HIB has all but been eliminated as a cause of bacteraemia and serious invasive infection.24

Streptococcus pneumoniae remains responsible for the majority of current cases of OB, but is thought to cause

invasive disease in less than 5% of these.29 In 2011, the 7 valent conjugate pneumococcal vaccine was replaced on

the National Immunisation Program with a 13 valent vaccine, covering most of the remaining invasive serotypes.

After two of the usual total three to four doses of these immunisations (usually achieved by four months of age in

Australia), there is >95% protection30 In addition the national program has increased herd immunity, which further

reduces the risk to all children.

If a child has a congenital immune deficiency syndrome, sickle cell disease, HIV, asplenia, cancer, nephrotic

syndrome, intracranial shunt, cochlear implant, immunosuppressive therapy or is indigenous then there is a greater

risk for SBI, independent of vaccination status.

Clinical appearance and toxicity

Think SEPSIS in any patient presenting with signs or symptoms that indicate possible infection. (SEPSIS Guideline)

Assessing paediatric patients to determine “toxicity” can be challenging, particularly if they are seen early in the

course of their febrile illness. The younger the patient, the more difficult this can be, even for seasoned paediatric

clinicians. A number of scoring and assessment systems have been devised in an attempt to provide a standardised

approach 31,19,20,33,34. More recent studies32 have cast doubt on their utility, and recognise the difficulties in

differentiating toxic and well-appearing infants. The younger the infant, the more important careful and repeated

clinical examination is, with close attention to vital signs.

The National Institute for Health and Clinical Excellence (NICE) guidelines combine features of specific serious

disease with general appearance into a traffic light system for identifying risk of serious illness35

CHQ-GDL-00707 – Febrile Illness

- 5 -

-

Green – low risk Amber – intermediate risk Red – high risk

Colour (of skin, lips

or tongue)

Normal colour Pallor reported by parent/carer Pale/mottled/ashen/blue

Activity Responds normally to social cues

Content/smiles

Stays awake or awakens quickly

Strong normal cry/not crying

Not responding normally to social cues

No smile

Wakes only with prolonged stimulation

Decreased activity

No response to social cues

Appears ill to a healthcare professional

Does not wake or if roused does not stay awake

Weak, high pitched cry or continuous cry

Respiratory

Nasal flaring

Tachypnoea:

RR > 50 bpm 6-12 mths

RR > 40 bpm > 12 mths

Oxygen saturation <95% in air

Crackles in the chest

Grunting

Tachypnoea: RR > 60 bpm

Moderate or severe chest indrawing

Circulation and

hydration

Normal skin and eyes

Moist mucous membranes

Tachycardia:

HR > 160 bpm age < 12 months

HR > 150 bpm age 12-24 mths

HR > 140 bpm age 2-5 years

Capillary refill time > 3 seconds

Dry mucous membranes

Poor feeding in infants

Reduced urine output

Reduced skin turgor

Other None of the amber or red symptoms or signs

Age 3-6 months, temperature > 39C

Fever for > 5 days

Rigors

Swelling of a limb or joint

Non weight bearing limb/not using an extremity

Age < 3 months, temperature > 38C

Non blanching rash

Bulging fontanelle

Neck stiffness

Status epilepticus

Focal neurological signs

Focal seizures

Table reproduced from NICE guideline: Feverish illness in children May 2013

Non-blanching rash and fever (Figure 1)

SBI incidence (predominantly meningococcal disease) has been estimated to be 2 - 8% in children with fever and

petechiae.30 If the child is unwell (i.e. abnormal vital signs, poorly perfused, or having altered mental state) or if the

rash is purpuric (>2mm lesions) and not consistent with typical Henoch-Schonlein purpura (HSP), then the child

should be managed presumptively for meningococcal disease with resuscitation as required and a 3rd generation

cephalosporin whilst investigations are carried out. Well-appearing febrile children with petechiae caused by local

pressure or only in the distribution of the superior vena cava (eg. following coughing/vomiting) may be discharged

with early review. In all other cases blood tests should be performed (full blood count, C reactive protein (CRP),

blood culture). If the FBC and CRP are within normal limits and the child remains well during a 4-hour period of

observation, then discharge with early review is again appropriate, otherwise admission with or without antibiotics

should be undertaken. 37-39 It should also be remembered that many viral infections can cause petechiae

CHQ-GDL-00707 – Febrile Illness

- 6 -

-

Figure 1: Fever and non-blanching rash flowchart

Fever & petechial rash Unwell (toxic)? Antibiotics +/- Fluid

Purpura present? Typical HSP picture

Mechanical cause or

SVC distribution only?

D/C after observation

with early review

FBC, CRP, CultureAdmit +/- Antibiotics

Y

N

N

N

Abnormal

Y

Y

N

Y

Normal FBC & CRP

Adapted from: Royal Children’s Hospital, Melbourne, ‘Fever and petechiae flowchart’

39

Fever height, duration and response to antipyretics

The height of the temperature has been used in many management algorithms to risk stratify febrile children. Whilst

there is evidence that higher temperatures are associated with increased risk of SBI 40,41 the significance and degree

of risk may be less clear in today’s immunised population. In addition, viruses such as influenza routinely cause

fevers >40°C, with SBI’s being responsible for only a small proportion of high fevers encountered. SBI’s such as

sepsis and meningitis may present without significant fever. The height of fever per se should therefore not be used

alone as the primary discriminating management decision variable, other than the group of infants less than 3

months in whom a temperature of greater than 38 degrees is classed as high risk.

The duration of the fever 42 and response to antipyretics 7 have failed to show any ability to differentiate severe from

mild illness or bacterial from viral infection.

Investigations

Most tests used to investigate febrile children have only moderately good sensitivities and specificities.

Investigations may be used to help make a diagnosis, determine antibiotic use and duration, or risk stratify certain

patients when no focus of infection is found on history and examination. In the case of a PUO, more extensive

investigations may be warranted, but will not be discussed further here.

A recent study67 validates a step by step approach to infants between 21 and 90 days, aiming to determine a low risk

group of infants who could safely be managed as outpatients without lumbar puncture nor empiric antibiotic

treatment. This approach sequentially evaluated the general appearance of the infant, results of urinalysis, and the

results of blood investigations including CRP and/or absolute neutrophil count. This approach was found to be

accurate and reliable in identifying patients who were low risk of invasive bacterial infection, and is reflected in our

flowchart for management of fever in infants in this age group.

CHQ-GDL-00707 – Febrile Illness

- 7 -

-

Urinalysis, microscopy and culture43-46 ( link to UTI guideline still being developed)

UTI is the most prevalent SBI in febrile young children and testing for one should be performed in symptomatic

children or in febrile children <3 years.

Dipstick urinalysis or urine microscopy may be used to screen urine samples for UTI. A diagnosis of UTI is likely

(positive likelihood ratios of >20) when:

both the leucocyte esterase and nitrite tests are positive in children ≥2 years or

bacteria are seen on a Gram stain.

A presumptive diagnosis of a UTI can then be made and empirical antibiotics commenced while the sample is being

cultured and tested for sensitivities.

UTI may be confidently ruled out (negative likelihood ratio of 0.19) when both leucocyte esterase and nitrite are

negative on dipstick testing in patients over two (2) years of age. If not, a sample for microscopy and culture should

be obtained.

The method of urine collection is also important and different methods vary by potential delays, invasiveness, and

contamination rates.

Supra-pubic bladder aspiration (SPA) has the lowest contamination rate, but is invasive and has a success rate of

23 - 90% depending on the operator and use of ultrasound to determine location and the presence of at least 20ml

of urine. It should be only generally considered in infants <6 months or if there is phimosis or labial adhesion, and

where possible should be guided by ultrasound.

Urethral catheterisation has a sensitivity of 95% and specificity of 99% compared to SPA. It is also invasive but

success rates may be higher than with SPA. It should be used first line in children >6 months who are not toilet-

trained or if SPA fails.

Clean catch specimen may be used for children who are unable to void on request, are not toxic, and in whom a

delay in obtaining the sample is not detrimental. The child’s perineum should be washed prior to collection and the

inside of the clean/sterile container used for collection should not contaminated by touching the collector’s or the

child’s skin. (Link to information sheet on collection of clean catch specimen once developed)

Midstream urine is recommended once the child is toilet trained.

Bag specimens although uncomfortable for the child (especially on removal) are often more acceptable to parents

and staff because they are less invasive. Unfortunately, up to 85 - 90% samples are contaminated and thus can

never be used for a culture. The high contamination rates plus potential delays in obtaining samples mean that bag

samples should generally be discouraged.

(Refer to UTI guideline – to be hyperlinked once developed)

Chest X-ray (CXR)

There is limited value in performing a CXR in a febrile child without cough. The likelihood of detecting pneumonia is

increased with longer duration of cough and fever or the presence of leucocytosis.17 Most pneumonia in infants and

young children is viral in origin and a CXR cannot reliably distinguish viral from bacterial pneumonia. Even when the

CXR suggests a bacterial aetiology, a virus is more often isolated than a bacterial pathogen.47

A CXR is recommended in febrile children with:48

increased work of breathing (chest recession, tracheal tug, use of accessory muscles)

cough, tachypnoea and low oxygen saturation (≤ 93% in room air)

a temperature >39°C and WBC >20 x 109 (as a screen for occult pneumonia).49,50

CHQ-GDL-00707 – Febrile Illness

- 8 -

-

Blood Culture

Although blood cultures are the gold standard for diagnosing a bacteraemia, there are limitations with this

investigation. Now that the incidence of occult bacteraemia is very low, the contamination rate is often higher than

the true positive rate. Negative blood culture may also have a poor NPV51 due in part to inadequate sampling

(minimum blood sample required usually ≥1 ml but confirm with local laboratory). Young infants have higher rates of

bacteraemia, and may become bacteraemic with other invasive SBI's, and it is recommended to collect a blood

culture in this group.

Full Blood Count

A systematic review found that WCC has no value in ruling out SBI in vaccinated children and is less valuable than

CRP for ruling in SBI32. This is supported by a recent prospective cohort study which found that total white cell count

and absolute neutrophil count were not sufficiently accurate to be used as triage tests for febrile children with

possible SBI66. Meningococcal, salmonella & staphylococcal bacteraemias often do not elevate the WCC. When

used, the threshold that has most often been used to indicate increased bacteraemia risk is WCC>15 x 109/L, which

has only moderate sensitivity and specificity. One large study including the post-PC vaccine era reported 74.0%

sensitivity, 54.5% specificity, 1.5% positive predictive value and a 99.5% negative predictive value.52 Some

investigators also include WCC<5 x 109/L, absolute neutrophils count (ANC)>10 x 109/L or <1 x 109/L, or the

presence of bands as risk factors.

With the current low risk of bacteraemia and using more appropriate tests for the other occult SBI, there appears

little value in the test, except in very young infants or the unimmunised, and even when used in these patient groups,

the results must always be correlated with clinical findings. .

C reactive protein (CRP)

CRP is an acute phase reactant and concentrations start to rise at four to six (4 - 6) hours after onset of

inflammation and peak around 36 - 50 hours. CRP is better than the FBC for detecting SBI, especially if used after

12 hours of fever.53 A recent systematic review suggested that different cut-off values could be used to identify high

risk and low risk children.32, however many of the papers included in this review predated pneumococcal

immunisation, and the findings must be interpreted with this in mind. This review found that a CRP of >80 mg/L was

associated with a 72% risk of SBI, and a CRP of <20 mg/L was associated with a 5% risk of SBI. This review

discussed the difficulty of nominating a lower level of CRP below which treatment was not necessary, balancing the

need to minimise the number of children with SBI who would be missed, and the desire to avoid over treating

children with antibiotics. Another recent paper67 stated that a CRP of > 20 mg/L suggested intermediate risk for

invasive bacterial infection in infants between 22 and 90 days. The current NICE guideline supports the use of CRP

in evaluation of febrile children, but does not nominate specific values to guide treatment. This guideline does not

nominate a cut off CRP value and recognises that decisions should always be made in conjunction with clinical

assessment and where available, review by experienced paediatric clinicians. There may be a role for serial CRP

measurements to guide management.

Serum electrolytes, glucose and venous blood gas

These should be considered as guided by the clinical assessment. Lactate can be used as a marker of possible

early sepsis – Refer to Sepsis; Recognition and Early Emergency Management in Children Guideline

CHQ-GDL-00707 – Febrile Illness

- 9 -

-

Lumbar Puncture (LP)

There is limited evidence regarding which children should have an LP performed as part of the septic workup,

especially as the incidence of bacterial meningitis has decreased dramatically since the introduction of the HIB and

PC vaccines. Although there is good evidence for several useful clinical features which influence the likelihood of

meningitis in a child, no one clinical feature is diagnostic 54 and in the very young infant meningitis often presents

with non-specific features like poor feeding, lethargy or irritability. The height of the fever and WCC are unhelpful as

they do not reflect the risk of bacterial meningitis. In general, as long as the child is well enough to tolerate the

procedure and there are no contraindications the procedure, an LP should be considered in children with signs or

symptoms of meningitis, or in the young febrile infant with non-specific features such as vomiting, lethargy /

drowsiness, irritability or poor feeding. [Refer to Acute Management of Meningitis in Children Clinical

Guideline]

Other tests

Procalcitonin (a prohormone rises with physiological stress) has restricted availability currently, but has shown

utility in differentiating bacterial from viral illness.55 It has been reported to have better specificity and possibly

sensitivity than CRP for bacterial meningitis or sepsis especially in first six to eight (6 - 8) hours of fever.56-58At

present this test is not widely available and is not part of the investigations performed in the emergency department

setting.

Viral diagnostic studies – limited usefulness in ruling out SBI as noted above.

Stool microscopy and culture – may be indicated in very young infant or if mucoid, bloody or prolonged diarrhoea.

Management

The recommended emergency management of febrile children is summarised on the Flowcharts (Appendix 1 and Appendix 2) and comprises:

Supportive

The child should have excess layers of clothing removed. Over-enthusiastic physical cooling can be counterproductive by stimulating shivering and other heat-retaining reflexes. Oral fluids if tolerated should be encouraged to maintain hydration.

Antipyretics

Antipyretics may be prescribed for an awake child to provide relief from discomfort caused by the fever or the underlying cause of the fever. Parents should be advised that fever is one of the body’s immune system responses to infection and that antipyretics do not treat or shorten the illness, will not prevent febrile convulsions,59 and if the dosing is excessive can cause adverse events.60

Aspirin should be avoided in children as the uncommon possibility of Reye's syndrome increases with varicella or influenza-like illnesses.61

Appropriate choices for symptomatic relief one of:

Paracetamol 15mg/kg up to four hourly with a maximum of four doses per day, or

Ibuprofen 10mg/kg up to six hourly with a maximum of four doses per day (avoid in children <6 months, if

significantly dehydrated 60 or history of hypersensitivity.

CHQ-GDL-00707 – Febrile Illness

- 10 -

-

There is some evidence that ibuprofen reduces fever and discomfort more quickly than paracetamol.63 The popular

dual therapy dosing regimes advocated by some reduce the time with fever, however there is no significant

difference in resolution of discomfort versus monotherapy.64 Safety concerns have been raised over recommending

two drugs with different dosing regimes for little gain, and parents should be specifically advised against this35

Risk Stratification

The risk of SBI may be stratified by age, the presence of a focus for infection, and toxicity. See the Flowcharts in Appendix 1 and Appendix 2 for details.

Antibiotics

Antibiotics may be indicated depending upon the perceived risk of SBI or the specific infection found. Antibiotics are usually administered via the intravenous route initially for admitted patients.

For choices and doses see CHQ Paediatric Antibiocard: Empirical Antibiotic Guidelines

See flowcharts Appendix 1 - Emergency Management of Fever in Children (< 4 months) and

Appendix 2 - Emergency Management of Fever in Children (≥4 months).

Disposition

As indicated by the Flowchart. All children who appear unwell should be reviewed early by a senior medical officer.

Febrile children fit for discharge should be discussed with a senior doctor and arrangements made for a follow up visit at his / her local General Practitioner to check progress and outstanding test results.

See flowchart Appendix 3 - Admission / discharge criteria for children presenting with fever.

When a decision is made to transfer a child to a Level 6 facility, referral must be made through RSQ.65

Activation of the QLD emergency medical system coordination centre (QCC)

Further information on the preparation of a infant prior to transport can be obtained through RSQ Clinical Guidelines paediatric section (page 31-35).65

Statewide RSQ clinical guidelines - Paediatrics

Supporting documents

Procedures, Guidelines and Protocols

Emergency management of children presenting with fever – less than 4 months

Emergency management of children presenting with fever – greater / equal to than 4 months

Admission / discharge criteria for children presenting with fever

Fever in children fact sheet

CHQ Paediatric Antibiocard: Empirical Antibiotic Guidelines

Sepsis: Recognition and Early Management in Children Guideline

Meningitis: Emergency Management in Children Guideline

Consultation

Key stakeholders who reviewed this version:

Dr Fiona Thomson, Paediatric Emergency Physician, LCCH

CHQ-GDL-00707 – Febrile Illness

- 11 -

-

Dr Sarah Martin, Paediatric Emergency Physician, LCCH

Dr Julia Clarke, Infection Management and Prevention Director, LCCH

Children’s Health Queensland would like to acknowledge the contribution made by the Greater Brisbane Metropolitan Area Clinical Procedures Working Group who developed the original guideline.

Definition of terms

Term Definition

AAP American Academy of Pediatrics

ANC Absolute neutrophil count

BSL Blood sugar level

Children 0-14 years of age

CHQ Children’s Health Queensland

CRP C-reactive protein

CXR Chest x-ray

E.Coli Escherichia coli

FBC Full blood count

HIB Haemophilus influenzae type B

HIV Human immunodeficiency virus

HSP Henoch-schonlein purpura

IV Intravenous

LP Lumbar puncture

MCS Microscopy, culture and sensitivity pathology test

NICE National Institute for Health and Clinical Excellence

NPV Negative predictive value

OB Occult bacteraemia

PC Pneumococcal

PUO Pyrexia of unknown origin

RSQ Retrieval Services Queensland

SBI Serious bacterial infection

SPA Supra-pubic bladder aspiration

SVC Superior vena cava

UTI Urinary tract infection

UEC Urea, electrolytes and creatinine

WCC White cell count

YOS Yale observation score

CHQ-GDL-00707 – Febrile Illness

- 12 -

-

References

1. Hewson, P., Poulakis, Z., Jarman, F., Kerr, J., McMaster, D., Goodge, J., Silk, G. (2000), ‘Clinical markers of serious illness in young infants: a multicentre follow-up study’, Journal of Paediatrics & Child Health, Vol. 36(3): pp. 221-5.

2. Brogan, P.A., Raffles, A. (2000), ‘The management of fever and petechiae: making sense of rash decisions’, Arch Dis Child, Vol. 83: pp. 506-7.

3. Klinkhammer, M.D., Colletti, J.E. (2008), ‘Pediatric myth: fever and petechiae’, CJEM, Vol. 10(5): pp. 479-82.

4. The Royal Children’s Hospital Melbourne. (2011), Clinical Practice Guidelines: Fever and Petechiae, [online] Available at: http://www.rch.org.au/clinicalguide/guideline_index/Fever_and_Petechiae_Purpura/ [Cited November 2011]

5. Trautner, B.W.,Caviness, A.C., Gerlacher, G.R. et al. (2006), ‘Prospective evaluation of the risk of serious bacterial infection in children who present to the emergency department with hyperpyrexia (temperature of 106°F or higher)’, Pediatrics, Vol. 118(1): pp. 34–40.

6. Kuppermann, N., Fleisher, G., Jaffe, D. (1998), ‘Predictor of occult pneumococcal bacteraemia in young febrile children’, Ann Emerg Med, Vol. 31(6): pp. 679-87.

7. Teach, S.J., Fleisher, G.R. (1997), ‘Duration of fever and its relationship to bacteremia in febrile outpatients 3 to 36 months old: the occult bacteremia study group’, Pediatr Emerg Care,Vol. 13(5): pp.317–9.

8. American Academy Paediatrics (AAP). (2011), ‘Urinary Tract Infection: Clinical Practice Guideline for the diagnosis and management of the initial UTI in febrile infants and children 2-24 months’, Pediatrics, Vol.128(3): pp. 595-610.

9. Williams, G.J., Macaskill, P., Chan, S.F., Turner, R.M., Hodson, E., Craig, J.C. (2010), ‘Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis’, Lancet Infect Dis, Vol. 10: pp. 240–50

10. Doley, A., Nelligan, M. (2003), ‘Is a negative dipstick urinalysis good enough to exclude urinary tract infection in Paediatric Emergency Department patients?’, Emergency Medicine, Vol. 15: pp. 77-80.

11. National Institute for Health and Clinical Excellence. (2007). Urinary tract infection in children. Diagnosis, treatment and long-term management, [online] Available at: http://www.nice.org.uk/nicemedia/live/11819/36032/36032.pdf [cited August 2007].

12. Bettenay, F.A., de Campo, J.F., McCrossin, D.B. (1988), ‘Differentiating bacterial from viral pneumonias in children’, Pediatr Radiol. Vol. 18(6): pp. 453-454.

13. Mower, W.R., Sachs, C., Nicklin, E.L., Baraff, L.J. (1997), ‘Pulse oximetry as a fifth pediatric vital sign’, Pediatrics, Vol. 99(5): pp. 681–6.

14. American College of Emergency Physicians Clinical Policies Committee. (2003). ‘Clinical Policies Subcommittee on Pediatric Fever. Clinical policy for children younger than three years presenting to the emergency department with fever’, Ann Emerg Med, Vol. 42(4): pp. 530–45.

15. Rutman et al. (2009), ‘Radiographic pneumonia in young, highly febrile children with leucytosis before and after universal conjugate pneumococcal vaccination’, Pediat Emerg Care, Vol. 25(1): pp.1-7.

16. Connell et al. (2007), ‘How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children’s hospital’, Pediatrics, Vol. 119 (5): pp. 891-6.

17. Herz, A.M., Greenhow, T.L., Alcantara, J., Hansen, J., Baxter, R.P., Black, S.B., Shinefield, H.R. (2006), ‘Changing epidemiology of outpatient bacteremia in 3 to 36-month old children after the introduction of the heptavalent-conjugated pneumococcal vaccine’, Pediatr Infect Dis J, Vol. 25: pp. 293-300.

18. Pratt, A., Attia, M.W. (2007), ‘Duration of fever and markers of serious bacterial infection in young febrile children’, Pediatrics International, Vol. 49: pp. 31–35

19. Curtis et al. (2010), ‘Clinical features suggestive of meningitis in children: a systematic review of prospective data’, Pediatrics, Vol. 126(5): pp. 952-60.

20. Maniaci, V., Dauber, A., Weiss, S., Nylen, E., Becker, K.L., Bachur, R. (2008), ‘Procalcitonin in young febrile infants for the detection of serious bacterial infections’, Pediatrics, Vol. 122(4): pp. 701-10

21. Lopez, A.F., Cubells, C.L., Garcia, J.J., Pou, J.F. (2003), ‘Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants: results of a multicenter study and utility of a rapid qualitative test for this marker’, Pediatr Infect Dis J, Vol. 22: pp.895–903.

22. Andreola, B., Bressan, S., Callegaro, S., Liverani, A., Plebani, M., Da Dalt, L. (2007), ‘Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department’, Pediatr Infect Dis J, Vol. 26: pp. 672–7.

23. Olaciregui, I., Hernández, U., Muñoz, J.A., Emparanza, J.I., Landa, J.J. (2009), ‘Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin’, Arch Dis Child, Vol. 94: pp. 501-5.

CHQ-GDL-00707 – Febrile Illness

- 13 -

-

24. Steering Committee on Quality Improvement and Management. (2008), ‘Subcommittee on Febrile Seizures. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures’, Pediatrics, Vol. 121(6): pp.1281-6.

25. Sullivan, J.E., Farrar, H.C. (2011), ‘Section On Clinical Pharmacology And Therapeutics And Committee On Drugs. Fever and Antipyretic Use in Children’, Pediatrics, Vol. 127: pp. 580

26. James, S. (2004), ‘Review of Aspirin / Reye’s syndrome warning statement. Medicines Evaluation Committee, Therapeutic Goods Administration’, [online] Available at: http://www.tga.gov.au/pdf/archive/review-aspirin-reyes-syndrome-0404.pdf [cited April 2004].

27. Kanabar, D., Dale, S., Rawat, M. (2007), ‘A review of ibuprofen and acetaminophen use in febrile children and the occurrence of asthma-related symptoms’, Clin Ther, Vol. 29(12): pp. 2716-23.

28. Perrott, D.A., Piira, T., Goodenough, B., Champion, G.D. (2004), ‘Efficacy and safety of acetaminophen vs ibuprofen for treating children’s pain or fever: a meta-analysis’, Arch Pediatr Adolesc Med, Vol. 158(6): pp. 521-6.

29. Hay, A.D., Costelloe, C., Redmond, N.M., Montgomery, A.A., Fletcher, M., Hollinghurst, S. et al. (2009), ‘Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial’, BMJ, Vol. (2008):337: pp. a1302 & Erratum in: BMJ, Vol. (2009):339: pp. b3295.

30. Statewide Clinical Coordination and Retrieval Services, (Queensland Health). (2008), ‘Clinical guidelines: Section two’, Queensland Health website, [intranet / online] Available at: http://qheps.health.qld.gov.au/rts/docs/clin_guide_pt2.pdf [cited July 25].

31. De S, Williams GJ, Hayen A et al. Value of white cell count in predicting serious bacterial infection in febrile children under 5 years of age. Arch Dis Child 2014;99:493-499.

32. Van den Bruel. (2011), ‘Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review’, BMJ, Vol. 342: pp. d3082.

33. Dagan, R., Powell, K.R., Hall, C.B., Menegus, M.A. (1985), ‘Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis’, J Pediatr, Vol.107(6): pp.855–60.

34. Jaskiewicz, J.A., McCarthy, C.A., Richardson, A.C., White, K.C., Fisher, D.J., Dagan, R. Powell, K.R. (1994), ‘Febrile infants at low risk for serious bacterial infection - an appraisal of the rochester criteria and implications for management’, Pediatrics, Vol. 94(3): pp.390-6

35. National Institute for Health and Clinical Excellence. (2013), ‘Feverish illness in children. Assessment and initial management in children younger than 5 years’, [online] Available at: http://publications.nice.org.uk [cited May 2013]

36. Hewson, P., Poulakis, Z., Jarman, F., Kerr, J., McMaster, D., Goodge, J., Silk, G. (2000), ‘Clinical markers of serious illness in young infants: a multicentre follow-up study’, Journal of Paediatrics & Child Health, Vol. 36(3): pp. 221-5.

37. Brogan, P.A., Raffles, A. (2000), ‘The management of fever and petechiae: making sense of rash decisions’, Arch Dis Child, Vol. 83: pp. 506-7.

38. Klinkhammer, M.D., Colletti, J.E. (2008), ‘Pediatric myth: fever and petechiae’, CJEM, Vol. 10(5): pp. 479-82.

39. The Royal Children’s Hospital Melbourne. (2011), Clinical Practice Guidelines: Fever and Petechiae, [online] Available at: http://www.rch.org.au/clinicalguide/guideline_index/Fever_and_Petechiae_Purpura/ [Cited November 2011]

40. Trautner, B.W.,Caviness, A.C., Gerlacher, G.R. et al. (2006), ‘Prospective evaluation of the risk of serious bacterial infection in children who present to the emergency department with hyperpyrexia (temperature of 106°F or higher)’, Pediatrics, Vol. 118(1): pp. 34–40.

41. Kuppermann, N., Fleisher, G., Jaffe, D. (1998), ‘Predictor of occult pneumococcal bacteraemia in young febrile children’, Ann Emerg Med, Vol. 31(6): pp. 679-87.

42. Teach, S.J., Fleisher, G.R. (1997), ‘Duration of fever and its relationship to bacteremia in febrile outpatients 3 to 36 months old: the occult bacteremia study group’, Pediatr Emerg Care,Vol. 13(5): pp.317–9.

43. American Academy Paediatrics (AAP). (2011), ‘Urinary Tract Infection: Clinical Practice Guideline for the diagnosis and management of the initial UTI in febrile infants and children 2-24 months’, Pediatrics, Vol.128(3): pp. 595-610.

44. Williams, G.J., Macaskill, P., Chan, S.F., Turner, R.M., Hodson, E., Craig, J.C. (2010), ‘Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis’, Lancet Infect Dis, Vol. 10: pp. 240–50

CHQ-GDL-00707 – Febrile Illness

- 14 -

-

45. Doley, A., Nelligan, M. (2003), ‘Is a negative dipstick urinalysis good enough to exclude urinary tract infection in Paediatric Emergency Department patients?’, Emergency Medicine, Vol. 15: pp. 77-80.

46. National Institute for Health and Clinical Excellence. (2007). Urinary tract infection in children. Diagnosis, treatment and long-term management, [online] Available at: http://www.nice.org.uk/nicemedia/live/11819/36032/36032.pdf [cited August 2007].

47. Bettenay, F.A., de Campo, J.F., McCrossin, D.B. (1988), ‘Differentiating bacterial from viral pneumonias in children’, Pediatr Radiol. Vol. 18(6): pp. 453-454.

48. Mower, W.R., Sachs, C., Nicklin, E.L., Baraff, L.J. (1997), ‘Pulse oximetry as a fifth pediatric vital sign’, Pediatrics, Vol. 99(5): pp. 681–6.

49. American College of Emergency Physicians Clinical Policies Committee. (2003). ‘Clinical Policies Subcommittee on Pediatric Fever. Clinical policy for children younger than three years presenting to the emergency department with fever’, Ann Emerg Med, Vol. 42(4): pp. 530–45.

50. Rutman et al. (2009), ‘Radiographic pneumonia in young, highly febrile children with leucytosis before and after universal conjugate pneumococcal vaccination’, Pediat Emerg Care, Vol. 25(1): pp.1-7.

51. Connell et al. (2007), ‘How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children’s hospital’, Pediatrics, Vol. 119 (5): pp. 891-6.

52. Herz, A.M., Greenhow, T.L., Alcantara, J., Hansen, J., Baxter, R.P., Black, S.B., Shinefield, H.R. (2006), ‘Changing epidemiology of outpatient bacteremia in 3 to 36-month old children after the introduction of the heptavalent-conjugated pneumococcal vaccine’, Pediatr Infect Dis J, Vol. 25: pp. 293-300.

53. Pratt, A., Attia, M.W. (2007), ‘Duration of fever and markers of serious bacterial infection in young febrile children’, Pediatrics International, Vol. 49: pp. 31–35

54. Curtis et al. (2010), ‘Clinical features suggestive of meningitis in children: a systematic review of prospective data’, Pediatrics, Vol. 126(5): pp. 952-60.

55. Maniaci, V., Dauber, A., Weiss, S., Nylen, E., Becker, K.L., Bachur, R. (2008), ‘Procalcitonin in young febrile infants for the detection of serious bacterial infections’, Pediatrics, Vol. 122(4): pp. 701-10

56. Lopez, A.F., Cubells, C.L., Garcia, J.J., Pou, J.F. (2003), ‘Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants: results of a multicenter study and utility of a rapid qualitative test for this marker’, Pediatr Infect Dis J, Vol. 22: pp.895–903.

57. Andreola, B., Bressan, S., Callegaro, S., Liverani, A., Plebani, M., Da Dalt, L. (2007), ‘Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department’, Pediatr Infect Dis J, Vol. 26: pp. 672–7.

58. Olaciregui, I., Hernández, U., Muñoz, J.A., Emparanza, J.I., Landa, J.J. (2009), ‘Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin’, Arch Dis Child, Vol. 94: pp. 501-5.

59. Steering Committee on Quality Improvement and Management. (2008), ‘Subcommittee on Febrile Seizures. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures’, Pediatrics, Vol. 121(6): pp.1281-6.

60. Sullivan, J.E., Farrar, H.C. (2011), ‘Section On Clinical Pharmacology And Therapeutics And Committee On Drugs. Fever and Antipyretic Use in Children’, Pediatrics, Vol. 127: pp. 580

61. James, S. (2004), ‘Review of Aspirin / Reye’s syndrome warning statement. Medicines Evaluation Committee, Therapeutic Goods Administration’, [online] Available at: http://www.tga.gov.au/pdf/archive/review-aspirin-reyes-

syndrome-0404.pdf [cited April 2004].

62. Kanabar, D., Dale, S., Rawat, M. (2007), ‘A review of ibuprofen and acetaminophen use in febrile children and the occurrence of asthma-related symptoms’, Clin Ther, Vol. 29(12): pp. 2716-23.

63. Perrott, D.A., Piira, T., Goodenough, B., Champion, G.D. (2004), ‘Efficacy and safety of acetaminophen vs ibuprofen for treating children’s pain or fever: a meta-analysis’, Arch Pediatr Adolesc Med, Vol. 158(6): pp. 521-6.

64. Hay, A.D., Costelloe, C., Redmond, N.M., Montgomery, A.A., Fletcher, M., Hollinghurst, S. et al. (2009), ‘Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial’, BMJ, Vol. (2008):337: pp. a1302 & Erratum in: BMJ, Vol. (2009):339: pp. b3295.

CHQ-GDL-00707 – Febrile Illness

- 15 -

-

65. Statewide Clinical Coordination and Retrieval Services, (Queensland Health). (2008), ‘Clinical guidelines: Section two’, Queensland Health website, [intranet / online] Available at: http://qheps.health.qld.gov.au/rts/docs/clin_guide_pt2.pdf [cited July 25].

66. De S, Williams GJ, Hayen A et al. Value of white cell count in predicting serious bacterial infection in febrile children under 5 years of age. Arch Dis Child 2014;99:493-499.

67. Gomez, B, Mintegi, S, Bressan, S et al “Validation of the “Step by Step” Approach in the Management of Young Febrile Infants” Pediatrics 2016; 138(2):e20154381

Audit/evaluation strategy

Level of risk High

Strategy 1. Staff survey to evaluate awareness of procedure and emergency management practices

2. Observe practice

3. Review documentation, i.e. chart audit, to evaluate compliance with procedure

Audit/review tool(s)

attached

Nil

Audit/Review date Annual snapshot review (August)

Review responsibility Individual Greater Brisbane Metropolitan hospitals, i.e. Ipswich, Logan, Redland, MCH, RCH,

TPCH, Redcliffe, Caboolture

Key elements / Indicators

/ Outcomes

KPI 1 — greater than 80% staff awareness of procedure

KPI 2 — greater than 80% compliance with procedure

Procedure revision and approval history

Version No. Modified by Amendments authorised by Approved by

1.0 Director, Paediatric Emergency

Medicine

Greater Brisbane metropolitan

area Children’s Health

Queensland

Chief Executive, Children’s

Health Queensland

2.0 Director, Paediatric Emergency

Medicine

Divisional Director, Critical Care Executive Director Hospital

Services

Keywords Children; fever; febrile; temperature; emergency management; admission, discharge criteria, 00707

Accreditation

references

NSQHS Standards 3, 4

EQuIPNational Standard 12

Appendices

Appendix 1: Emergency Management of Children with Fever (<4 months)

Appendix 2: Emergency Management of children with Fever (>4 months)

Appendix 3: Admission / Discharge Criteria for Children with Fever

CHQ-GDL-00707 – Febrile Illness

- 16 -

-

Appendix 1: Emergency Management of Children with Fever (< 3 months)

Emergency Management of children with FEVER (< 3 MONTHS)

Assess Severity

Consider pre-hospital management given

Treat discomfort with antipyretic

Remove excess layers of clothing

Early senior review

C

Toxic features A

No Toxic features

Investigations

Urine MCS

FBC

CRP

Blood culture

LP C +/- CXR B

Typical respiratory illness

See Bronchiolitis guideline

Not a typical respiratory

illness

Investigations

Consider urine MCS

Investigations

Urine MCS

FBC

CRP

Blood culture

+/- CXR B +/- LP C

A. Toxic Marked Lethargy/decrease in

activity

Altered mental status

Inconsolable irritability

Tachypnoea, increase work of breathing, grunting, weak cry

Cyanosis

Poor perfusion (mottled skin, pallor, mottled)

Marked/persistent tachycardia > 180

Moderate to severe dehydration

Infant feeding <50% normal

< 4 wet nappies in 24 hours

Seizures

Petechial or purpuric rash

Do not underestimate parental concern

B. CXR indications Increased work of breathing

Cough

Tachypnoea

SaO2 ≤ 93% in room air

T > 39°C & WCC > 20 x 109

C LP indications

age < 2 months

vomiting

lethargy/drowsiness

cerebral irritability

poor feeding

caution if marked drowsiness

CONTRAINDICATIONS to LP

Focal neurological signs

Reduced level of consciousness

Haemodynamic instability

Respiratory compromise Antibiotics as per

CHQ Antibiocard

(HYPERLINK)

28 days –

3 months

Age ≤ 28

days

Any high risk

features? D

Meets

discharge

criteria?

Discharge Admit to children’s

inpatient service

Emergency Management as

per SEPSIS guideline

D. High risk criteria

ANC < 1 or > 10 x 109/L

Bands > 1.5 x 109/L

CSF:> 7 WBC

Urine microscopy: >10 WBC or bacteria

CXR: Infiltrate, collapse

Consider prematurity

Immunodeficiency or significant underlying chronic disease

Y

Y

N

N

As

se

ss

me

nt

Inve

sti

gati

on

s &

Tre

atm

en

t R

evie

w

Child presents to emergency services with a fever > 380 C

Dis

po

sit

ion

CHQ-GDL-00707 – Febrile Illness

- 17 -

-

Appendix 2: Emergency Management of Children with Fever (≥ 3 months)

Emergency Management of children with FEVER (≥ 3 MONTHS)

Assess Severity

Consider pre-hospital management given

Treat discomfort with antipyretic

Remove excess layers of clothing Close attention to vital signs/CEWT

Toxic A

OR

Immunocompromised

No Toxic features A

Emergency Management

as per SEPSIS guideline

A. Toxic Marked Lethargy/decrease in

activity

Altered mental status

Inconsolable irritability

Tachypnoea, work of breathing, grunt, weak cry

Poor perfusion (mottled skin, pallor)

Marked/persistent tachycardia

Moderate to severe dehydration

Seizures

Petechial or purpuric rash (see text)

Do not underestimate

parental concern

Discuss with senior

doctor and consider

antibiotics

Focus of infection

evident?

(including bronchiolitis)

Any features

suggesting

SBI? D

Meets

discharge

criteria?

Discharge Discuss with senior

doctor re disposition

– admission vs early

clinical review

B. CXR indications Increased work of breathing

Cough

Tachypnoea

SaO2 ≤ 93% in room air

T > 39°C & WCC > 20 x 109/L

Child presents to emergency services with a fever > 380 C

C. LP indications

Vomiting/lethargy/drowsiness

cerebral irritability/poor feeding

CONTRAINDICATIONS to LP

Focal neurological signs

Reduced level of consciousness

Haemodynamic instability

Respiratory compromise

D. Features suggestive of SBI

WCC > 15 x 109/L if not fully

immunised

ANC < 1 or > 10 x 109/L

Bands > 1.5 x 109/L

CSF:> 7 WBC

Urine micro: >10 WBC or bacteria

CXR: Infiltrate, collapse

Immunodeficiency/chronic disease

Y

N

As

se

ss

me

nt

Inve

sti

gati

on

s &

Tre

atm

en

t R

evie

w

Dis

po

sit

ion

Investigations

Urine for urinalysis +/- MCS

FBC and CRP

Blood culture

+/- CXR B +/- LP C

≥ 2 doses of

immunisations

(Hib + PCV)?

Investigate and treat

as indication by

specific infection

Investigations

Urine for urinalysis +/- MCS if fever for > 48 hours

Antibiotics if

results suggest

UTI

N

N

N

Y

Y

Y

CHQ-GDL-00707 – Febrile Illness

- 18 -

-

Appendix 3 – Admission / Discharge Criteria for Children with Fever

Criteria for admission to children’s inpatient service

Criteria for admission to the children’s inpatient service for an infant with

febrile illness includes:

age less than 2 months

any toxic features

need for intravenous antibiotics

significant high risk criteria for SBI

inability to maintain adequate oral intake to maintain hydration

unplanned return within 24 hours of initial assessment

social factors such as long distance to hospital and family/carers not

able to cope with symptom management.

Criteria for discharge from the emergency service

Criteria for discharging an infant with febrile illness from the emergency

service includes:

age greater than 2 months

no toxic features

no indication for intravenous antibiotics

no high risk criteria for SBI

able to maintain adequate oral intake to maintain hydration

parent information sheet given and discussed

recommend review by GP within 24 hours

When discharging an infant with a febrile illness, their social circumstances

should be considered and appropriately addressed after the initial

assessment and observation period:

time of day

parents/carers comprehension and compliance

access to transport should return be required

distance to local hospital