He’s always sick: ENT infections and immunodeficiency

Cite this article as:
Alasdair Munro. He’s always sick: ENT infections and immunodeficiency, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20243

Otis is a 3yr old boy presenting to the emergency department with fever, and purulent discharge from his left ear. He otherwise looks well, however, his mother mentions this is his third ear infection since he was born, and he always seems to have a cough and a cold. She asks you if there could be a problem with his immune system?

Some children seem to have constant ear, nose or throat infections during childhood. We know that for a small, but important minority of children this may be the presenting feature of a primary immunodeficiency. Let’s look at how these may present, when to think of it, and what to do about it.

Primary immunodeficiency is rare

It’s worth stating from the outset, that the majority of children with recurrent ENT infections will not have a primary immunodeficiency. There is a relatively common phenomenon called “physiological immunodeficiency of infancy”, where-by there is a natural nadir in immunoglobulin levels as maternal immunoglobulin fades, and the child’s own immune system has only just become able to produce immunoglobulin for itself. This is at its lowest between 3-6 months and normally resolves by age 1. However, fully developed protection against encapsulated organisms doesn’t reach maturity until between 2-5 years, and IgA production doesn’t reach adult levels until adolescence. It can be completely normal for young children to suffer 4-11 respiratory infections a year (depending on exposure, e.g. siblings, nursery, etc.)

When should I suspect immunodeficiency?

When considering the characteristics of infections that should trigger suspicion for immunodeficiency, we should be thinking about:

More severe infections than is usual

Combined immunodeficiency disorders (affecting both cellular and humoral immunity), such as severe combined immunodeficiency (SCID), present in the first 3-6 months with severe, life-threatening infection. Unusually aggressive infections should prompt further investigation

Infections with unusual organisms

Infections with certain pathogens can point towards specific diagnoses, including respiratory infections with Pseudomonas aeruginosa (think cystic fibrosis or primary ciliary dyskinesia), oral/oesophageal candidiasis (think HIV or chronic granulomatous disease), upper respiratory infections with Pneumocystis carinii (think HIV or other T cell deficiencies) or recurrent otitis/sinusitis with Neisseria meningitidis (think complement deficiency).

Finally, to a lesser extent:

Frequency of infection

This is the least predictive of immunodeficiency, given the discussion above. Very frequent sinopulmonary infections in younger children with encapsulated bacteria can be the presenting feature of the rare condition X-linked agammaglobulinaemia (XLA: boys who produce no immunoglobulins). In late childhood and adolescence, the same presentation in a milder form may be a sign of combined, variable immunodeficiency (CVID), which is a heterogeneous group of disorders of antibody production.

Other, rare conditions include chronic granulomatous disease (CGD) which may present with deep abscesses of the outer ear or mastoid, or HIV presenting with recurrent otitis media (normally with other associated features)

 

When to refer

Some general guidelines have been produced by the Jeffrey Modell foundation for when to consider referral for immunodeficiency workup:

  • Four of more new ear infections within 1 year
  • Two or more serious sinus infections within 1 year
  • Two or more months on antibiotics with little effect
  • Two or more pneumonias within 1 year
  • Failure of an infant to gain weight or grow properly
  • Recurrent, deep skin or organ abscesses
  • Persistent thrush in the mouth or fungal infection on skin
  • Need for intravenous antibiotics to clear infections
  • Two or more deep-seated infections including septicaemia
  • A family history of primary immunodeficiency

Although having a low specificity, they provide a useful framework when thinking of children with more severe infections than usual.

 

Should I do some tests?

If considering referral, there are definitely some basic tests are useful to do first (if the child is severely unwell, don’t wait for tests to refer).

Full blood count

This is useful for ANY suspected immunodeficiency. Persistent lymphopaenia in a child <2yrs should prompt screening for SCID.

NB: It can be normal to have transient lymphopaenia or neutropaenia in isolation in young children following a viral illness. Incidental neutropaenia does not need repeat testing if there are no concerns about underlying immunodeficiency.

Immunoglobulins

IgG, IgM and IgA levels are useful to investigate children with recurrent ENT/airway infections.

It is also worth considering an HIV test if symptoms are consistent, but ensure you have a discussion with parents before testing.

If both FBC and immunoglobulins are normal in the setting of recurrent infections, it is perfectly acceptable to wait for 3 -6 months to see if the condition improves before referral.

 

Conclusions

  • Primary immunodeficiencies are rare but important, and ENT infections may be the presenting feature
  • The severity of infection and presence of opportunistic pathogens are a much stronger predictor than the frequency of infections
  • Basic tests such as FBC and Immunoglobulins should be performed in children prior to/pending referral if they are not severely unwell
  • Consider investigation and referral for primary immunodeficiency early in children with severe infections and failure to thrive, or those with family history

Further reading: https://www.entmasterclass.com/ENT_Journal_2019_Interactive.pdf page 9

Bumper Bubble Wrap PLUS – July/August 2019

Cite this article as:
Anke Raaijmakers. Bumper Bubble Wrap PLUS – July/August 2019, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20544

Here is our latest Bumper BubbleWrap Plus, combining July’s and August’s paediatric Journal Club Lists provided by Professor Jaan Toelen & his team of the University Hospitals in Leuven (Belgium). This comprehensive list of ‘articles to read’ from the last two months comes from 34 journals, including Pediatrics, The Journal of Pediatrics, Archives of Disease in Childhood, JAMA Pediatrics, Journal of Paediatrics and Child Health, NEJM, and many more. This list features answers to intriguing questions such as: ‘Which oxygen saturation leads to ROP?’, ‘How much do parents actually use their smartphones?’, ‘Does teaching of parents lead to less urine contamination rates?’ and ‘Is delayed cord clamping beneficial in elective caesarians?’. We hope you enjoy it!

You will find the list is broken down into four sections:

1.Reviews and opinion articles

Debate: Are Stimulant Medications for Attention-Deficit/Hyperactivity Disorder Effective in the Long-Term?

Cortese S, et al. J Am Acad Child Adolesc Psychiatry. 2019 Jun 26

Continuous Noninvasive Carbon Dioxide Monitoring in Neonates: From Theory to Standard of Care.

Hochwald O, et al.Pediatrics. 2019 Jun 27.

Hyperinsulinaemic hypoglycaemia-an overview of a complex clinical condition.

Kostopoulou E, et al.Eur J Pediatr. 2019 Jun 26.

Food allergy desensitisation: a hard nut to crack?

Chong KW, et al.Arch Dis Child. 2019 Jun 26.

The two extremes meet: pediatricians, geriatricians and the life-course approach.

Cesari M, et al.Pediatr Res. 2019 Jun 25.

What I Learned From My Childhood as a Patient: Internalized Messages About Bodies.

Robertson AD. JAMA Pediatr. 2019 Jun 24

Group B Streptococcus: Trials and Tribulations.

Davies HG, et al. Pediatr Infect Dis J. 2019 Jun;38(6S Suppl 1):S72-S76

Parasites in Human Stool: To Ignore or Not To Ignore?

Butters C, et al.Pediatr Infect Dis J. 2019 Jun;38(6S Suppl 1):S47-S51.

Dilemmas With Rotavirus Vaccine: The Neonate and Immunocompromised.

Chiu M, et al.Pediatr Infect Dis J. 2019 Jun;38(6S Suppl 1):S43-S46.

To LP or not to LP? Identifying the Etiology of Pediatric Meningitis.

Mijovic H, et al.Pediatr Infect Dis J. 2019 Jun;38(6S Suppl 1):S39-S42

Viral Bacterial Interactions in Children: Impact on Clinical Outcomes.

Diaz-Diaz A, et al.Pediatr Infect Dis J. 2019 Jun;38(6S Suppl 1):S14-S19.

Biomarkers for Infection in Children: Current Clinical Practice and Future Perspectives.

Stol K, et al.Pediatr Infect Dis J. 2019 Jun;38(6S Suppl 1):S7-S13.

Innate immunity and urinary tract infection.

Ching C, et al.Pediatr Nephrol. 2019 Jun 13

Stranded on Antipsychotics: Role of the Pediatric Clinician.

Ballard R, et al.Clin Pediatr (Phila). 2019 Jun 10:9922819853774

Update on adrenal steroid hormone biosynthesis and clinical implications.

Bacila IA, et al.Arch Dis Child. 2019 Jun 7.

Stimulating and maintaining spontaneous breathing during transition of preterm infants.

Dekker J, et al.Pediatr Res. 2019 Jun 19.

School Readiness.

Williams PG, et al. Pediatrics. 2019 Jul 22.

Controversies Surrounding the Pathophysiology of Tics.

Singer HS, et al. J Child Neurol. 2019 Jul 18:883073819862121.

Viral hepatitis.

Hardikar W. J Paediatr Child Health. 2019 Jul 17.

Two centuries of immunisation in the UK (part 1).

Lang S, et al. Arch Dis Child. 2019 Jul 4.

Two centuries of immunisation in the UK (part II).

Lang S, et al. Arch Dis Child. 2019 Jul 13.

Family Chaos and Asthma Control.

Weinstein SM, et al. Pediatrics. 2019 Jul 9.

Torsion of an Undescended Testis – A Surgical Pediatric Emergency.

Kargl S, et al. J Pediatr Surg. 2019 Jun 28.

Less invasive surfactant administration (LISA): chances and limitations.

Herting E, et al. Arch Dis Child Fetal Neonatal Ed. 2019 Jul 11.

2. Original clinical studies

Randomized Controlled Trial of Iron-Fortified versus Low-Iron Infant Formula: Developmental Outcomes at 16 Years.

Gahagan S, et al. J Pediatr. 2019 Jun 25.

Benefits of medical clowning in the treatment of young children with autism spectrum disorder.

Shefer S, et al.Eur J Pediatr. 2019 Jun 26.

Social Robots for Hospitalized Children.

Logan DE, et al.Pediatrics. 2019 Jun 26.

Tic Suppression in Children With Recent-Onset Tics Predicts 1-Year Tic Outcome.

Kim S, et al.J Child Neurol. 2019 Jun 26:883073819855531.

Delays in diagnosis of nephrotic syndrome in children: A survey study.

Hollis A, et al.Paediatr Child Health. 2019 Jul;24(4):258-262.

Shared decision making during antenatal counselling for anticipated extremely preterm birth.

Barker C, et al.Paediatr Child Health. 2019 Jul;24(4):240-249.

Parental preferences on diagnostic imaging tests for paediatric appendicitis.

Martinez-Rios C, et al.Paediatr Child Health. 2019 Jul;24(4):234-239

Neurologic Outcome After Prematurity: Perspectives of Parents and Clinicians.

Lemmon ME, et al.Pediatrics. 2019 Jun 27.

Development of the Serum α-Fetoprotein Reference Range in Patients with Beckwith-Wiedemann Spectrum.

Duffy KA, et al.J Pediatr. 2019 Jun 21

Positional plagiocephaly/brachycephaly is associated with later cognitive and academic outcomes.

Knight S. J Pediatr. 2019 Jul;210:239-242.

Confidentiality in the Doctor-Patient Relationship: Perspectives of Youth Ages 14-24 Years.

Zucker NA, et al.J Pediatr. 2019 Jun 20.

Characteristics Associated with Successful Weight Management in Youth with Obesity.

Gorecki MC, et al.J Pediatr. 2019 Jun 20.

Achieved oxygen saturations and retinopathy of prematurity in extreme preterms.

Gantz MG, et al.Arch Dis Child Fetal Neonatal Ed. 2019 Jun 22.

Defining urinary tract infection by bacterial colony counts: a case for less than 100,000 colonies/mL as the threshold.

Tullus K. Pediatr Nephrol. 2019 Jun 20.

Cervical Spine Injury Risk Factors in Children With Blunt Trauma.

Leonard JC, et al.Pediatrics. 2019 Jun 20.

Immature neutrophils in young febrile infants.

Ramgopal S, et al.Arch Dis Child. 2019 Jun 20.

Recurrent Pneumococcal Meningitis in Children: A Multicenter Case-Control Study.

Darmaun L, et al.Pediatr Infect Dis J. 2019 Jun 17.

Educational intervention does not reduce non-invasive urine contamination rates in children presenting to the emergency department.

Jacob R, et al.J Paediatr Child Health. 2019 Jun 19.

Short Sleep Duration and Later Overweight in Infants.

Tuohino T, et al.J Pediatr. 2019 Jun 14.

Assessing the Efficacy of Very Early Motor Rehabilitation in Children with Down Syndrome.

Okada S, et al.J Pediatr. 2019 Jun 14.

Assessment and management of tic disorders and Tourette syndrome by Australian paediatricians.

Efron D, et al. J Paediatr Child Health. 2019 Jun 17.

Association of Sexting With Sexual Behaviors and Mental Health Among Adolescents: A Systematic Review and Meta-analysis.

Mori C, et al. JAMA Pediatr. 2019 Jun 17.

Mental Illness Among Youth With Chronic Physical Conditions.

Adams JS, et al.Pediatrics. 2019 Jun 14. pii: e20181819.

Predicting risk of underconfidence following maternity leave.

van Boxel E, et al.Arch Dis Child. 2019 Jun 14.

Children’s views on taking medicines and participating in clinical trials.

Nordenmalm S, et al.Arch Dis Child. 2019 Jun 14.

The Right Stuff: Priming Students to Focus on Pertinent Information During Clinical Encounters.

Stuart E, et al.Pediatrics. 2019 Jun 13.

Sleep macro-architecture and micro-architecture in children born preterm with sleep disordered breathing.

Chan M, et al.Pediatr Res. 2019 Jun 13.

How much do parents actually use their smartphones? Pilot study comparing self-report to passive sensing.

Yuan N, et al.Pediatr Res. 2019 Jun 13.

Neurodevelopmental and Academic Outcomes in Children With Orofacial Clefts: A Systematic Review.

Gallagher ER, et al.Pediatrics. 2019 Jun 12.

Diaphragm electromyography results at different high flow nasal cannula flow rates.

Jeffreys E, et al.Eur J Pediatr. 2019 Jun 11.

Challenges to Pertussis Control.

Edwards KM. Pediatrics. 2019 Jun 10.

Acellular Pertussis Vaccine Effectiveness Over Time.

Zerbo O, et al. Pediatrics. 2019 Jun 10.

Safety and Efficacy of Low Dose Domperidone for Treating Nausea and Vomiting Due to Acute Gastroenteritis in Children.

Leitz G, et al. J Pediatr Gastroenterol Nutr. 2019 Jun 7.

Endotracheal intubation skills of pediatricians versus anesthetists in neonates and children.

van Sambeeck SJ, et al.Eur J Pediatr. 2019 Jun 8.

Acid Suppression Therapy and Symptom Improvement (or Lack Thereof) in Children.

Boruta M, et al.Pediatrics. 2019 Jun 7.

Early Acid Suppression Therapy Exposure and Fracture in Young Children.

Malchodi L, et al.Pediatrics. 2019 Jun 7.

Fatigue in childhood chronic disease.

Nap-van der Vlist MM, et al.Arch Dis Child. 2019 Jun 7.

Patterns of Electrolyte Testing at Children’s Hospitals for Common Inpatient Diagnoses.

Tchou MJ, et al.Pediatrics. 2019 Jun 6.

A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection.

Aronson PL, et al.Pediatrics. 2019 Jun 5.

Prediction Models for Febrile Infants: Time for a Unified Field Theory.

Kuppermann N, et al.Pediatrics. 2019 Jun 5.

The etiological evaluation of sensorineural hearing loss in children.

van Beeck Calkoen EA, et al.Eur J Pediatr. 2019 May 31.

Exome sequencing in the assessment of congenital malformations in the fetus and neonate.

Mone F, et al.Arch Dis Child Fetal Neonatal Ed. 2019 Jul;104(4):F452-F456.

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis.

Wilson MR, et al. N Engl J Med. 2019 Jun 13;380(24):2327-2340.

Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment.

Natarajan G, et al. Pediatrics. 2019 Jul 23.

Asymptomatic Pharyngeal Carriage of Kingella kingae Among Young Children in Vancouver, British Columbia, Canada.

Masud S, et al. Pediatr Infect Dis J. 2019 Jul 16.

Under-immunization of pediatric transplant recipients: a call to action for the pediatric community.

Feldman AG, et al. Pediatr Res. 2019 Jul 22.

Secular Trends in Pubertal Growth Acceleration in Swedish Boys Born From 1947 to 1996.

Ohlsson C, et al. JAMA Pediatr. 2019 Jul 22.

Male Pubertal Timing-Boys Will Be Men, but When?

Curtis VA, et al. JAMA Pediatr. 2019 Jul 22.

Association of Sleep Problems and Melatonin Use in School-aged Children.

Koopman-Verhoeff ME, et al. JAMA Pediatr. 2019 Jul 22.

Dietary Treatment with Extensively Hydrolyzed Casein Formula Containing the Probiotic Lactobacillus rhamnosus GG Prevents the Occurrence of Functional Gastrointestinal Disorders in Children with Cow’s Milk Allergy.

Nocerino R, et al. J Pediatr. 2019 Jul 18.

Observational study of cytomegalovirus from breast milk and necrotising enterocolitis.

Patel RM, et al. Arch Dis Child Fetal Neonatal Ed. 2019 Jul 20.

Pyuria as a Marker of Urinary Tract Infection in Neurogenic Bladder: Is It Reliable?

Su RR, et al. Pediatr Infect Dis J. 2019 Aug;38(8):804-807.

Does caffeine prevent incubation in babies with bronchiolitis who present with apnoea?

Hosheh O, et al. Arch Dis Child. 2019 Jul 20.

Fructose malabsorption in asymptomatic children and in patients with functional chronic abdominal pain: a prospective comparative study.

Martínez-Azcona O, et al. Eur J Pediatr. 2019 Jul 19.

Time course of nocturnal cough and wheezing in children with acute bronchitis monitored by lung sound analysis.

Koehler U, et al. Eur J Pediatr. 2019 Jul 18.

Assessing the appropriateness of the management of otitis media in Australia: A population-based sample survey.

Clay-Williams R, et al. J Paediatr Child Health. 2019 Jul 17.

Predictors for hospital admission of asymptomatic to moderately symptomatic children after drowning.

Cohen N, et al. Eur J Pediatr. 2019 Jul 16.

Rapid Influenza Testing in Infants and Children Younger than 6 Years in Primary Care: Impact on Antibiotic Treatment and Use of Health Services.

van Esso DL, et al. Pediatr Infect Dis J. 2019 Aug;38(8):e187-e189.

Respiratory Virus Epidemiology Among US Infants With Severe Bronchiolitis: Analysis of 2 Multicenter, Multiyear Cohort Studies.

Hasegawa K, et al. Pediatr Infect Dis J. 2019 Aug;38(8):e180-e183.

Association of Screen Time and Depression in Adolescence.

Boers E, et al. JAMA Pediatr. 2019 Jul 15.

DNA Viremia Is Associated with Hyperferritinemia in Pediatric Sepsis.

Simon DW, et al. J Pediatr. 2019 Jul 11.

Attention-Deficit/Hyperactivity Disorder Medication and Unintentional Injuries in Children and Adolescents.

Ghirardi L, et al. J Am Acad Child Adolesc Psychiatry. 2019 Jul 11.

Hyponatremia in children under 100 days old: incidence and etiologies.

Storey C, et al. Eur J Pediatr. 2019 Jul 13.

Neonatal Abstinence Syndrome and Associated Neonatal and Maternal Mortality and Morbidity.

Lisonkova S, et al. Pediatrics. 2019 Jul 12.

Effect of intrapartum antibiotics on the intestinal microbiota of infants: a systematic review.

Zimmermann P, et al. Arch Dis Child Fetal Neonatal Ed. 2019 Jul 11.

Management of Infants at Risk for Group B Streptococcal Disease.

Puopolo KM, et al. Pediatrics. 2019 Jul 8.

In preterm infants, does fluid restriction, as opposed to liberal fluid prescription, reduce the risk of important morbidities and mortality?

Abbas S, et al. J Paediatr Child Health. 2019 Jul;55(7):860-866.

Problems of feeding, sleeping and excessive crying in infancy: a general population study.

Olsen AL, et al. Arch Dis Child. 2019 Jul 3.

Hearing Loss With Congenital Cytomegalovirus Infection.

Foulon I, et al. Pediatrics. 2019 Jul 2.

Delayed Cord Clamping versus Early Cord Clamping in Elective Cesarean Section: A Randomized Controlled Trial.

Cavallin F, et al. Neonatology. 2019 Jul 2:1-8.

Prematurity as an Independent Risk Factor for the Development of Pulmonary Disease.

Fierro JL, et al. J Pediatr. 2019 Jun 28.

Clinical Characteristics of Primary HHV-6B Infection in Children Visiting the Emergency Room.

Hattori F, et al. Pediatr Infect Dis J. 2019 Jun 20.

3. Guidelines and Best Evidence

Risk of Meningitis in Infants Aged 29 to 90 Days with Urinary Tract Infection: A Systematic Review and Meta-Analysis.

Nugent J, et al.J Pediatr. 2019 Jun 20.

Medical care for migrant children in Europe: a practical recommendation for first and follow-up appointments.

Schrier L, et al.Eur J Pediatr. 2019 Jun 26.

Mask versus Prongs for Nasal Continuous Positive Airway Pressure in Preterm Infants: A Systematic Review and Meta-Analysis.

King BC, et al.Neonatology. 2019 Jun 4:1-15.

Heart Rate Monitoring in Newborn Babies: A Systematic Review.

Anton O, et al.Neonatology. 2019 Jun 27:1-12.

Impact of Cystic Fibrosis on Unaffected Siblings: A Systematic Review.

Chudleigh J, et al.J Pediatr. 2019 Jul;210:112-117.e9.

Probiotics for cow’s milk protein allergy: a systematic review of randomized controlled trials.

Qamer S, et al.Eur J Pediatr. 2019 Jun 22.

Do probiotics help babies with infantile colic?

Rivas-Fernández M, et al.Arch Dis Child. 2019 Jun 22.

A new simple formula built on the American Academy of Pediatrics criteria for the screening of hypertension in overweight/obese children.

Di Bonito P, et al. Eur J Pediatr. 2019 Jun 18.

A Simpler Prediction Rule for Rebound Hyperbilirubinemia.

Chang PW, et al.Pediatrics. 2019 Jun 13.

What evidence-based strategies have been shown to improve breastfeeding rates in preterm infants?

Hilditch C, et al.J Paediatr Child Health. 2019 Jun 22.

Fluids in the management of sepsis in children: a review of guidelines in the aftermath of the FEAST trial.

Dewez JE, et al. Arch Dis Child. 2019 Jul 20.

What paediatricians need to know about the updated 2017 American Heart Association Kawasaki disease guideline.

Phuong LK, et al. Arch Dis Child. 2019 Jul 3.

4. Case Reports

Acute ataxia in a healthy 19-month-old girl.

Jia JL, et al.Paediatr Child Health. 2019 Jul;24(4):218-220.

Recurrent Acute Septic Arthiris caused by Kingella Kingae in a 16-month-old boy

Chosidow A, et al.Pediatr Infect Dis J. 2019 Jun 20.

Hypotonia and Lethargy in a Two-Day-Old Male Infant.

Long AH, et al.Pediatrics. 2019 Jun 21.

‘A bugging feeling’: a live foreign body in the ear.

Calleja T. Arch Dis Child. 2019 Jun 8.

Somatic symptom disorder should be suspected in children with alleged chronic Lyme disease.

Peri F, et al.Eur J Pediatr. 2019 Jun 29.

When Acute Stridor Is More Than Croup.

Miller MR, et al. J Pediatr. 2019 Jul 11.

Spontaneous mediastinal abscess of curious causation.

Stratton H, et al. J Paediatr Child Health. 2019 Jul;55(7):873-874.

An Unusual Presentation of Failure to Thrive.

Baldwin KP, et al. Clin Pediatr (Phila). 2019 Jul 3:9922819857738.

 

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

Unlucky dip: Rational diagnostic testing for infections

Cite this article as:
Alasdair Munro. Unlucky dip: Rational diagnostic testing for infections, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20311

We see lots of children with suspected infections. Modern microbiology techniques have opened up a huge array of tests: some new and expensive, but we are often still reliant on good old fashion microscopy and culture.

With so many tests so readily available, we need to think hard about diagnostic stewardship. This means testing the right patients for the right reasons. We must be wary of over-diagnosis, preventing confusion, anxiety or unnecessary treatment, and making choices that represent good value. Many tests can be expensive and are often not necessary to make management decisions.

With that in mind, let’s take a look at some of the most common diagnostic tests for infections, and when we should (or shouldn’t!) be deploying them.

 

Urine dips and MC&S

Urinary tract infections (UTIs) are the most common serious bacterial infection in high-income countries. There are many departments where it is routine to set up every febrile child to get a “clean catch” urine as soon as they arrive. This is unwise, because it is VERY EASY to contaminate a urine sample from a clean catch. We have all seen children or parents putting their hands/feet/face in the bowl, and let’s be honest – if the child is sitting on the container, it’s basically directly under the body’s primary waste pipe.

Accepting a decent risk of false positives, we must aim to test only those who need the test. So when should we do it?

Fever without a source

This is the primary indication for doing a urine dip, and it is a sensible one. However, still not every child with fever and no source needs a urine dip. Older children can report urinary symptoms, and the absence of these makes a UTI much less likely. In addition, by school age, UTIs in males with normal renal tracts become very rare, so urine testing also becomes less useful.

As a framework, urine dips should be performed in the following groups with fever and no source (assuming they have no risk factors for UTIs and have no red flags):

Outside of these groups, use your clinical discretion to decide if the pre-test probability justifies the risk of a false positive – take into consideration the child’s age, gender, duration of symptoms, how unwell they appear, and obviously if they have known risk factors such as renal abnormalities or previous UTIs.

Symptoms of UTI

This seems obvious – but it’s worth stating that once urinary symptoms are present (increased frequency, dysuria) you should dip the urine to check for infection, and it may be worth sending samples for MC&S even if they are dip negative in this scenario (you can withhold treatment pending results).

It is worth taking more care for children with non-urinary symptoms, such as abdominal pain or vomiting (which is probably not predictive of UTI). Once at school age (particularly in boys) these symptoms are unlikely to be a symptom of a UTI so a higher threshold for testing should be adopted.

Some people say that all children with rigors require urine testing. Rigors are not evidenced to have any influence on the risk of UTI (or any significant risk of bacterial infection). If there is another source of the fever, urine dip is certainly not indicated on the basis of a rigor alone.

For more information on relative risks for UTIs in younger children, the supplementary materials to the UTI risk calculator study make an interesting read.

What about hot babies with bronchiolitis?

This becomes a slightly more controversial topic, and decisions require risk stratification based on the age of the child. For example, a febrile neonate with bronchiolitis might be lucky to escape the full shebang of a septic screen anyway – and a quick in/out catheter is unlikely to yield a false positive.

The literature on this topic is a bit confusing because of varying definitions of UTI and bronchiolitis (some studies including any child with RSV detected in their nose). The most recent meta-analysis with more stringent criteria for diagnosing UTI found a rate of concomitant UTI with bronchiolitis of 0.8% – low enough that testing is not advised.

Bottom line: if an infant has a fever and a clinical diagnosis of bronchiolitis, then urine dip is not necessary in most instances – however this should be given strong consideration in infants <60d and should be performed in neonates.

 

Blood culture

For a full myth busting exercise in blood cultures, please read the recent DFTB post on this topic. Some things to bear in mind if you’re thinking of taking a blood culture:

  • You are testing for bacteraemia. If you do not suspect bacteraemia, do not send a blood culture.
  • Blood cultures are extremely low yield in uncomplicated skin/soft tissue infection and pneumonia and should be avoided.
  • You do not need to wait for a fever to take a blood culture – it has no influence on the likelihood of obtaining a positive result. If you suspect bacteraemia, take the culture now.
  • If you are going to take a blood culture, aim to inoculate at least 1ml of blood per year of the child’s age. Less than this and you increase the risk of contamination and decrease the sensitivity.

 

Wound swab

When it comes to swabbing for microscopy, culture and sensitivity (MC&S), there is a golden rule*:

Do not swab any non-sterile site that you have not already clinically diagnosed as being infected.

A skin swab, throat swab, eye swab etc. will grow bacteria 100% of the time, because these places are non-sterile. They will often grow pathogens, because many pathogens are quite happy just being colonisers a lot of the time, and actually some of them are more often found as bystanders than as trouble-makers (Pseudomonas aeruginosa is a prime example – it is very rarely pathogenic in non-sterile sites). A positive swab does not diagnose infection.

YOU have to diagnose infection; a swab will just tell you what bacteria is causing it.

I would like to give a special shout out to gastrostomies at this point – just because they are “mucky” is not a good reason to swab. If you do swab it, you will find good old Pseudomonas (it loves playing in wet stuff). Skin and soft tissue infections are red, hot and inflamed +/- a bit of pus. Yellowish clearish greenish stuff is normally just serous fluid, so don’t worry about it and don’t swab it!

The same goes for babies sticky eyes. If you swab it, it will grow bacteria, but this tells you nothing about whether they are infected. Look for inflammation, if you find it then diagnose infection, treat empirically and send a swab if you are concerned about resistant bacteria.

*there are some exceptions to the golden rule, including burns and chronic wounds in immunosuppressed patients.

 

Throat swabs

Before starting – let’s remember that you cannot diagnose a bacterial throat infection with a swab alone. If you are considering swabbing a throat for MC&S, you must have already clinically diagnosed infection.

Guidelines vary quite widely in their recommendations to swab or not swab when diagnosing tonsillitis. It is worth considering that a throat swab has a reasonable sensitivity for group A Strep, if performed correctly. Sadly – we are all dreadful at performing throat swabs in children (who are usually very good at not wanting a throat swab), and often get a good dose of tongue and palate. Not good.

A further thing to consider is that approximately half of all throat swabs positive for group A Strep just indicate carriage – you’ve found the bug, but it’s just a bystander.

This means that if you swab and haven’t found the bacteria, it might be there but you’ve missed it, and if you have found it, there’s a 50% chance it’s not causing the illness anyway…

If it’s extremely important you detect the presence of group A Strep (for example in populations high risk for rheumatic fever) then I would definitely do a swab. If it’s not (and it usually is not), then make your decision to treat or not on clinical grounds alone.

Also, remember that in children <4yrs group A Strep tonsillitis is rare and almost never causes complications, so if you’re thinking of doing a throat swab for a child in this age group you need to have a very good reason.

 

Respiratory virus testing

Respiratory tract infections are extremely common in children. There is a fair amount of controversy and disagreement about the role for respiratory virus testing. It can have several roles:

  1. Local epidemiology. Some big/university hospitals like to keep track of what’s circulating, and will often have guidelines on who and when they want these tests performed.
  2. Cohorting. In bronchiolitis season, some hospitals might fill one bay with RSV and another with Rhinovirus. This is an evidence free zone.
  3. Fever without a source. Influenza in particular can cause horrible febrile illnesses in children without the classic respiratory prodrome. The idea is to detect the flu to prevent unnecessary antibiotics.

A group of children you should not test for respiratory viruses is anyone with cough and coryza. They do not need a test – they can be safely diagnosed clinically, and the presence or absence of a virus on testing does not change anything.

What about in lower respiratory tract infections? We can imagine that the discovery of a virus would prevent unnecessary antibiotics. However, respiratory viruses are common (even among non-hospitalised populations) and co-infection with bacteria is also common in viral infections. The presence of a virus does not preclude a bacterial infection. As such, their use in this context is contentious, and they do not appear to reduce antibiotic use.

For a thorough look at the principles and evidence of respiratory virus testing in children, I would recommend this excellent review paper.

 

Conclusions

  • Not every child with fever and no source needs a urine dip. Do it in infants, young girls and children with fever persisting >48hrs. Otherwise, use clinical discretion.
  • You probably don’t need to urine dip febrile children with clinical bronchiolitis.
  • Only do blood cultures if you suspect bacteraemia, and take lots of blood if you do.
  • Only send a swab for MC&S from a non-sterile site if you’ve already diagnosed infection.
  • Throat swabs are usually not useful. Only do them for high risk groups.
  • Respiratory virus testing is not useful in most circumstances. Only do it if you have a definite plan for how it will change your management.
  • When in doubt – if you can’t explain how the test will change your management, don’t do the test.

The 31st Bubble Wrap

Cite this article as:
Grace Leo. The 31st Bubble Wrap, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20429

Article 1: An egg a day keeps the doctor away? (Ecuador)

Ianotti LL, et al. Eggs in Early Complementary Feeding and Child Growth: A Randomized Controlled Trial. Pediatrics; 2017 July [epub] doi: 10.1542/peds.2016-3459

What’s it about?

Childhood stunting is contributed to by both biological factors and environmental factors such as poverty. The World Health Assembly has set a global target to reduce childhood stunting by 40% by 2025. Previous interventions to improve growth have included fortification of food and dietary supplementation. Utilising locally available nutritious food is an important step improving outcomes. Eggs have high nutritional value and contain high concentrations of choline, a nutrient previously found to promote growth in animal models.  There has been no previous study investigating the use of eggs as a complementary nutrition source for infants.

Why does it matter?

The study was completed in Cotopaxi Providence, a rural, indigenous population in Ecuador. This population is estimated to have a baseline prevalence of stunting of 38%. Children aged 6 to 9 months were randomised to treatment (1 egg per day for 6 months [n=83], and control (no intervention [n=80]). Children were excluded if they had a medical condition, severe malnutrition or egg allergy. Eggs were delivered on a weekly basis and a log report egg consumption, morbidities, and anthropometric measures were taken after 6 months. Egg intervention increased length-for-age z score by 0.63 (93% CI, 0.38-0.88, p<0.001), and weight-for-age z score by 0.61 (95% CI 0.45-0.77, p<0.001).  There was a reduced prevalence of stunting by 47% (prevalence ratio, 0.53; 95% CI, 0.37-0.77).  Children in the treatment group also had reduced intake of sugar-sweetened foods compared with control (PR, 0.71; 95% CI, 0.51-0.97 p=0.032). 

Clinically Relevant Bottom Line:

This study found that supplementing the diet 6 to 9-month-olds with an egg a day significantly improves linear growth and reduces stunting within a population from a developing country with a high prevalence of stunting (38%). There were no reports of allergic reactions. Care must be taken in applying this study to different contexts and cultural backgrounds.

Reviewed by: Lorraine Cheung

 

Article 2: Maternal influenza immunisation to improve infant outcome (Nepal)

Steinhoff MC, et al. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis. 2017 Sep;17(9):981-989

Why does it matter?

Influenza can cause serious illness in children, especially infants younger than 6 months of age. Immunisations are strongly recommended to pregnant woman and any child over 6 months of age. Maternal immunisation during pregnancy induces high levels of maternal antibodies that can be transferred to the foetus and prevents influenza virus infection both in pregnant women and their infants during their first few months of life.

What’s it about?

This randomised controlled trial assessed the safety and efficacy of maternal influenza immunisations in mothers and infants in Nepal, where Influenza viruses circulate perennially.  They recruited 3693 women in 17 to 34 weeks of gestation between 2011 to 2013. Maternal influenza immunisations were offered throughout the year, with 3629 infants included in the immunisation efficacy analysis.

The study found that influenza immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1-34).  Among infants followed from birth to six months of age, immunisation had an overall efficacy of 30% (95% CI 5-48. There was also a 42g increase in birth weight (95% CI: 8-76) among infants born to immunised mothers (with an overall decrease in low birth weight infants by 15%). There were no differences noted in the rates of small for gestational age infants or preterm birth. Both groups had a similar number of adverse events.

Clinically Relevant Bottom Line:

Maternal influenza immunisation reduced maternal influenza-like illness, influenza in infants and rates of low birth weight in Nepal. Maternal immunisation should be considered in subtropical regions where the virus is present for many months.

Reviewed by: Jessica Win See Wong

 

Article 3: Comparing infusion rates of fluid boluses in septic shock (India)

Sankar J et al. Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour of Resuscitation in Children With Septic Shock: A Randomized Controlled Trial. Pediatric Critical Care Medicine. 2017 Oct; 18(10)

What’s it about?

This was a randomised controlled trial where the researchers identified children with septic shock in paediatric ED and ICU in a tertiary hospital in northern India, and compared intravenous fluid boluses of 40-60mL/kg per hour in 20mL/kg aliquots delivered over 15-20 minutes versus over 5-10 minutes. Primary outcomes were the need for mechanical ventilation and/or impaired oxygenation. There were several other secondary objectives.

Subjects were aged 9 months to 12 years and included children with suspected infection with two or more clinical signs of decreased perfusion. They excluded children with dengue, malaria, severe anaemia, severe malnutrition, primary cardiac illness, those on non-invasive ventilation before developing shock, those who had already received fluids or inotropes, and those with contraindications to central line insertion.

This was a small RCT, with only 96 children randomised. The study was terminated after about 50% enrolment after interim analysis suggested harm in the 5-10 minute group. They found that children who received fluid boluses over 5-10 minutes were at higher risk of intubation and mechanical ventilation, had higher rates of intubation due to fluid overload, and had higher percentages of fluid overload in 24 hours. There was no difference in the mortality rate.

Why does it matter?

Recognition and treatment of sepsis is huge in acute paediatrics. Guidelines around the world recommend treating septic shock with fluid resuscitation of up to 60mL/kg as boluses, although the 2011 FEAST trial highlighted the potential harms of fluid boluses, suggesting a cautious approach to fluid bolus administration.

Instead of looking at different fluid volumes or types of fluid, this study compared infusion times. Unlike in the FEAST study, they excluded children vulnerable to the effects of fluid overload, allowing for more broad applicability of the results. Both groups of children received almost identical volumes of fluid as boluses; it was only the infusion times that differed.

The researchers suggested that rapid fluid bolus administration is difficult in developing countries due to a shortage of staff to administer the boluses, and fear of fluid overload and need for ventilation, which is not easy to achieve in resource-restricted settings.

The Bottom Line

Research is yet to identify the optimal fluid management of septic shock in developing and developed countries, so in the meantime caution is prudent.

Reviewed by: Katie Nash

 

Article 4: Think zinc! (India)

Negi K et al. Serum zinc, copper and iron status of children with coeliac disease on three months of gluten-free diet with or without four weeks of zinc supplements: a randomised controlled trial. Trop Doct. 2018; 48(2): 112-116. Doi: 10.1177/0049475517740312.

Why does it matter?

Coeliac disease is characterised by gluten intolerance which leads to damage to the small bowel mucosa via an autoimmune process in genetically susceptible individuals. Partial or total villous atrophy affects the maintenance of nutrients. Zinc is implicated in the improvement of mucosal healing and faster normalisation of micronutrient status in susceptible patients. Therefore, zinc supplementation may prove to be beneficial in patients with coeliac disease.

What’s it about?

This study compares the serum zinc, iron and copper status in paediatric patients following a gluten-free diet with or without zinc supplementation. All children aged <18 years with newly diagnosed coeliac disease were randomised to either the gluten-free diet (GFD) group or the glute-free diet + zinc supplementation (GFD+Zn) group via computer-generated random sequences. Patients were assessed with clinical history, examination and blood tests at baseline and various follow-up review up to 3 months. Unsurprisingly, iron, zinc and copper levels were below the normal range at baseline in all patients. The rise in haemoglobin, serum iron and ferritin levels was better in the GFD+Zn group than the GFD alone group. Otherwise, there was no significant difference in the rise of zinc, copper and weight gain in the two groups.

Clinically Relevant Bottom Line:

The study has shown that zinc supplementation significantly improves iron status but does not affect serum zinc or copper levels. The authors speculate this may be secondary to the contributory effect of zinc towards mucosal healing and improvement of intestinal absorption. Although interesting, it would have been helpful to couple these biochemical results with endoscopic findings with zinc supplementation. Nevertheless, the mainstay of treatment for coeliac disease remains the gluten-free diet and you may think of supplementing zinc if you want a faster improvement in iron status

Reviewed by: Jennifer Moon

 

Article 5: The power of playtime (Ethiopia)

Worku, B.N., et al  Effects of home-based play-assisted stimulation on developmental performances of children living in extreme poverty: a randomized single-blind controlled trial. BMC Paediatrics. 2018 Vol 18. doi: 10.1186/s12887-018-1023-0.

Why does it matter?

A child’s development is dependent on social, economic and environmental factors. In third world countries where children are brought up in extreme poverty, a multitude of factors negatively impacts their development. We know that early intervention can prevent developmental loss, in both developed and developing countries. The challenge is finding a sustainable way to deliver effective intervention.

What’s it about?

The study looked at foster children aged between 3 and 59 months, living with foster mothers in Jimma, a town in Ethiopia. The children were randomly assigned to intervention and control groups at a 1:1 ratio. The intervention group received home-based play stimulation once a week for 6 months, which focused on activities to promote developmental skills and mother-child interactions. The therapy was provided by a trained nurse, however, they also spent time teaching the foster mothers, so they could provide ongoing play therapy at home.

The assessors, who were blinded to the children’s allocations, used culturally specific and standardized developmental screening tools, at baseline, 3 months and 6 months. The study found that intervention was beneficial for language, social-emotional and personal-social performances (statistically significant for language [P = 0.0014], personal-social [P = 0.0087] and social-emotional [P < 0.0001] performances).

Clinically Relevant Bottom Line:

The study showed positive effects on multiple domains of development in the 6 months of follow up for children who received home-based play therapy. This approach is highly sustainable, as the foster mother’s acquired skills means they can continue to provide play therapy and hopefully, continue to have positive effects on children living in resource-limited settings.

Reviewed by: Tina Abi Abdallah

 

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments! We are also looking to expand the Bubble Wrap team so please contact us if you’re interested in this! That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to. 

Elbow examination

Cite this article as:
Becky Platt. Elbow examination, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19777

2-year-old Alfie presents to the Emergency department having sustained an injury jumping on the sofa and falling off at home an hour ago.  His older sister says she thinks he put his right hand out as he fell, landing on the carpet.  Alfie’s mum gave him a dose of paracetamol after the injury and brought him straight to the ED because his elbow looked so swollen.  Alfie looks pale and tearful.

Speaker pitches for DFTB20 are now open

Cite this article as:
Team DFTB. Speaker pitches for DFTB20 are now open, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19879

Planning for DFTB20 had begun before the balloons for DFTB19 had barely deflated. Coming back to Australia means warm weather, captivating coffee and another opportunity to catch up with friends old and new.

So so you have something you want to share? Do you want to speak at DFTB20? Do you know someone who would be amazing?

If so then just click this here….

Pitches will close on 1st of August so get them in now! We promise to give you access to two of the most accomplished speaker coaches in the world, Grace Leo and Ross Fisher. We promise the most engaged audience in the world of paediatrics.

Tickets will go on sale on the 1st of November 2019 but why not book your leave now?

*All speakers will need to register to be able to speak.

The 30th Bubble Wrap

Cite this article as:
Grace Leo. The 30th Bubble Wrap, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19868

Article 1: What’s the risk of infants 29-90 days having both UTI and meningitis?

Nugent, J., et al Risk of Meningitis in Infants Aged 29 to 90 Days with Urinary Tract Infection: A Systematic Review and Meta-Analysis. Journal of Paediatrics; 2019 June [eprint] doi: 10.1016/j.jpeds.2019.04.053

What’s it about?

UTI remains the most common serious bacterial infection in infants, and infants under 28 days routinely undergo a complete septic work up when presenting to ED with a fever. For infants aged between 29 – 90 days, the decision to LP is guided by clinical findings and left up to the treating physician. So, what are the chances that febrile baby with the positive urinalysis also has meningitis?

Why does it matter?

This systematic review looked at the pooled prevalence of co-existing meningitis, bacterial or aseptic. The authors searched 3 databases for studies reporting on the rates of meningitis in infants aged 29 – 90 days who had abnormal urinalysis or culture results (but were not necessarily febrile at presentation) who also had LPs performed as part of their work up. A total of 20 studies (3 prospective and 17 retrospective) were identified.

The review found the pooled prevalence of concomitant bacterial meningitis in infants with UTI was 0.25% (95% CI, 0.09%-0.70%). This translates to a number needed to investigate with LP for 1 diagnosis of meningitis of 400. The pooled prevalence for aseptic meningitis over the 20 studies was not able to be calculated, but in some studies the prevalence was as high as 29%.

Clinically Relevant Bottom Line:

Based on this systematic review, the risk of bacterial meningitis in infants aged 29-90 days with evidence of UTI is low, but the decision to LP should always take into consideration the clinical picture, as opposed to a calculated pre-test probability.

Reviewed by: Tina Abi Abdallah

Article 2: Anima sana in corpore sano: Does a healthy body equal a healthy soul?

Easterlin MC, et al. Association of Team Sports Participation With Long-term Mental Health Outcomes Among Individuals Exposed to Adverse Childhood Experiences. JAMA Pediatr. 2019 May 28 [Epub ahead of print].

What’s it about?

Adverse childhood experiences (ACEs) and/or mental health problems are unfortunately very common, but the impact and extent of these events may differ from person to person. This article addresses whether team sports may influence well being in adulthood after ACEs. ACEs were defined as physical and sexual abuse, emotional neglect, parental alcohol misuse, parental incarceration, and living with a single parent extracted from the data of the National Longitudinal Study of Adolescent to Adult Health (National Population sample of US adolescents – 1994 and 2008). Multivariable logistic regression models were used to score factors associated with team sport participation. About half of the participants (9668 individuals included in the study – 4888 (49.3%)) reported 1 or more ACEs. Among those with ACEs, team sports participation during adolescence was significantly associated with lower odds of receiving a diagnosis of depression, anxiety or having current depressive symptoms (adjusted odds ratios, 0.76, 0.70 and 0.85 respectively).

Why does it matter?

Adverse childhood experiences can have long-term mental health consequences, but the knowledge of factors improving mental health after these events is lacking. This study showed an association with team spots and improved mental health and could be an ‘easy’ tool to improve well being in traumatised children.

Clinically Relevant Bottom Line:

Team sport participation in adolescence was associated with better mental health outcomes in children with ACEs. As suggested by the authors, team sports may be an important and scalable resilience builder.

Reviewed by: Anke Raaijmakers 

Article 3: Another look at risk factors for cervical spine injury in children with blunt trauma

Leonard JC, et al. Cervical Spine Injury Risk Factors in Children with Blunt Trauma. Pediatrics 2019, 144 (1). doi.org/10.1542/peds.2018-3221

What’s it about?

Four tertiary care hospitals which are part of the USA based Paediatric Emergency Care Applied Research Network (PECARN) ran a prospective observational study to look at risk factors of cervical spine injury in children with blunt trauma. They then compared the PECARN model with a de novo model of risk factors. After screening  11809 children with blunt trauma, approximately were found to be eligible and 4144 children were enrolled. Of 4091 children, 1.8% (74) had a cervical spine injury.  Children who didn’t receive cervical spine imaging had medical record and subsequent call follow up (if no imaging) to verify the absence of injury.  Treating ED providers filled out electronic questionnaire prior to knowledge of cervical spine image results. These questionnaires assessed for risk factors including injury mechanism, patient variables and physical findings.

Fourteen risk factors were identified as having significant association with CSIs in this study. PECARN criteria currently include 8 risk factors (high-risk MVC, diving mechanism, conditions predisposing for CSI, neck pain, reported inability to move neck, altered mental status, limited neck range of motion on exam, substantial torso injury and focal neurological deficits). Three of these variables were not found to be independently associated with CSIs in the analysis of data collected: high risk MVC, conditions predisposing for CSI and limited neck range of movement on examination

A de novo model was proposed of 7 variables: diving mechanism, axial load, neck pain, reported inability to move neck, altered mental status, respiratory distress, and intubation.

Comparing PECARN with this de novo model slightly increased the sensitivity (90.5 to 91.9%) and specificity (45.6% to 50.3%). Extrapolated imaging rates using the PECARN and de novo risk model would decrease from 78.2% to 55.1% and 50.5% respectively and roughly halve CT scan. Both models missed children with CSIs – 7 in PECARN and 6 with the de novo model however on retrospective chart review 6 of the 7 missed children had a PECARN risk factor. None of those missed had surgical intervention but two were managed with medical devices (brace or rigid cervical collars).

The Bottom Line

This study presents data from 4 US trauma centres to improve identification of cervical spine injury risk factors in children. A de novo model with 7 risk factors has been examined and compared with the existing PECARN model and would yield slightly improved results and would have missed one less child with CSI in the group of over 4000 children studied.

Reviewed by: Grace Leo

Article 4: Drowning in the school holidays

Peden A et al. The association between school holidays and unintentional fatal drowning among children and adolescents aged 5-17 years. Journal of Paediatrics and Child Health. 2019 May; 55(5), pp. 533-538.

Why does it matter?

Australia is an island with 85% of its population living within 50 km of the coastal line. Thanks to a mostly temperate climate, many families and young people enjoy spending time at beaches, rivers and lakes, as well as many households having swimming pools. Therefore, drowning becomes a very real problem, especially for children and young people. In fact, drowning is a leading killer of young people, however children and adolescents aged 5-17 years have one of the lowest rates. This could be due to the protective effect of time spent in formal schooling and this study shows how the risk of drowning differs during time spent at school versus school holidays.

What’s it about?

The investigators extracted the data from the Australian Royal Life Saving National Fatal Drowning Database over 2005-2014. A total of 188 children/adolescents aged 5-17 years drowned during the study period. There was a significant difference between drowning incidence during school holidays (including public holidays) and school days (P value <0.01), with relative risk (RR) of drowning on a holiday being 2.40 times higher than on a school day (CI 1.82-3.18). The risk was higher for children 5-9 years (RR = 3.05; CI 1.98-4.72) than adolescents 10-17 years (RR = 2.02; CI 1.38-2.93). The risk was similar for males and females in this age group. Most drowning incidents occurred at a river, creek or stream, as opposed to a beach or swimming pool.

Clinically Relevant Bottom Line:

As might be expected the rate of drowning in children and adolescents is much higher during school holidays than during formal schooling (with this study finding a relative risk 2.4 times higher). Although there are limitations to this study,  it advocates for ongoing drowning risk reduction strategies but particularly in the lead-up to school holiday periods in school-aged children and adolescents.

Reviewed by: Jennifer Moon

Article 5: The global impact of rotavirus vaccine in children under 5 years of age

Aliabadi N, et al. Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008–16: ndings from the Global Rotavirus Surveillance Network. Lancet Glob Health 2019; 7: e893-903

Why does it matter?

In 2015, Rotavirus gastroenteritis  accounted for an estimated 250,000 deaths and 1·9 million episodes per year of severe acute gastroenteritis requiring hospital admis­sion in the under 5 year old age group. This paper cites that rotavirus vaccination has an efficacy of ranging from 57% to 85% for RV1 and from 45% to 90% for RV5 based on countries’ mortality strata. WHO recommends rotavirus vaccination as part of the national immunisation scheme for all countries. This study helps to assess the impact of introduction of rotavirus vaccinations.


What’s it about?

This paper presents the findings of the World Health Organisation (WHO) co-ordinated Global Rotavirus Surveillance Network (GRSN) to examine the rates of rotavirus confirmed hospital admissions prior to and following introduction of rotavirus vaccine globally between 2008-16 across 69 countries. Whilst it covers areas in Africa, the Americas, Eastern Mediterranean and European region, some of the countries the GRSN does not include are UK, American, Canadian, Russia, Australia or New Zealand. As China joined after 2016 it was also not included in the assessed population.

The prospective study looked at children under 5 years old admitted to hospital across the GRSN sites with acute gastroenteritis who subsequently had stool PCR within 48 hours to assess for rotavirus infection. It assessed the difference in cases pre and post-vaccine periods. The was a main analysis of data included sites with over 1 year of enrolment and over 100 specimens tested per year (305789 cases across 69 countries). Three further sensitivity analysis looked at cases 1) that did not have both pre and post vaccine data 2) regions with vaccine coverage <60% or vaccine not introduced, 3) Slightly relaxed lab inclusions to account for smaller labs. There was insufficient data to be able to combine these three groups. The study reports one third of children (32.9%) included had confirmed rotavirus gastroenteritis. Presentations of rotavirus gastroenteritis reduced 38% pre-vaccination to 23% post vaccination of cases included (with a relative reduction of 39.6%, CI 35.4-43.8). This data uses the mean proportion of children who were positive and the actual range between the two groups overlapped. The three other sensitivity analysis showed similar rates of overall reduction in rotavirus presentations.

The Bottom Line

This WHO-GSRN large impact analysis of rotavirus vaccination in children under 5 included 305,789 children, of which one third had confirmed rotavirus gastroenteritis. Between pre and post-vaccination periods, there was a relative decline in rotavirus gastroenteritis hospital presentations of almost 40%.  Rotavirus vaccination is effective in reducing hospital admissions for rotavirus gastroenteritis and should be considered for introduction in countries not yet covered such as part of Africa and southeast Asia.

(Ed note: If you’re interested in gastroenteritis, you may also be interested to know that Archives of Disease of Childhood has just published a systematic review and meta-analysis looking at Gelatin tannate (a protective gelatin with  astringent, antibacterial, and anti-inflammatory properties) in the use of acute diarrhoea and gastroenteritis in children. There was no difference with placebo).

Reviewed by: Grace Leo

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments! We are also looking to expand the Bubble Wrap team so please contact us if you’re interested in this! That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to. 

High Flow Nasal Cannula Oxygen: Franz Babl at DFTB18

Cite this article as:
Team DFTB. High Flow Nasal Cannula Oxygen: Franz Babl at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19674

Given that DFTB18 was held in Melbourne it was important to highlight the work of PREDICT (the Paediatric Research In Emergency Department International Collaborative)* This talk, by Franz Babl, centred around the management of bronchiolitis and focussed on the recent PARIS trial.

Ben Lawton took a closer look at the trial here and you can see the infographic we developed to go with the paper below.

You can find the paper here.

So what does the expert think? Here is A/Professor Franz Babl from the Melbourne stage.

Selected references

O’Brien S, Borland ML, Cotterell E, Armstrong D, Babl F, Bauert P, Brabyn C, Garside L, Haskell L, Levitt D, McKay N. Australasian bronchiolitis guideline. Journal of paediatrics and child health. 2019 Jan;55(1):42-53.

Haskell L, Tavender EJ, Wilson C, O’Brien S, Babl FE, Borland ML, Cotterell L, Schuster T, Orsini F, Sheridan N, Johnson D. Implementing evidence-based practices in the care of infants with bronchiolitis in Australasian acute care settings: study protocol for a cluster randomised controlled study. BMC pediatrics. 2018 Dec;18(1):218.

Schlapbach LJ, Straney L, Gelbart B, Alexander J, Franklin D, Beca J, Whitty JA, Ganu S, Wilkins B, Slater A, Croston E. Burden of disease and change in practice in critically ill infants with bronchiolitis. European Respiratory Journal. 2017 Jun 1;49(6):1601648.

*COI – Both Ben and Andy have done or are doing work under the auspices of PREDICT

This talk was recorded live at DFTB18 in Melbourne, Australia. With the theme of ‘Science and Story‘ we pushed our speakers to step out of their comfort zones and consider why we do what we do. Caring for children is not just about acquiring the scientific knowhow but also about taking a look beyond a diagnosis or clinical conundrum at the patient and their families.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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The missing component of clinical practice

Cite this article as:
Damian Roland. The missing component of clinical practice, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19685

This is an extract of the talk I gave at #DFTB19 highlighting an important research ethos – the full talk will be released via the Don’t Forget the Bubbles at a later date.

The Doctor” is a painting by Luke Fildes and was first exhibited in 1891.

The Doctor exhibited 1891 Sir Luke Fildes 1843-1927 Presented by Sir Henry Tate 1894 https://www.tate.org.uk/art/work/N01522

The artist had lost his son Philip at the age of one and the scenes reflects the admiration that he had had for the doctor who had looked out for him. 

For some the painting may represent a stereotypical view of medicine in the past – the doctor rubbing his chin in a wise fashion, the child prostrate on a make-shift bed. And there is a parent figure in the background, watching on anxiously. 

This painting has had a revival recently despite being over 100 years old. It highlights the triad of care we all know exists in paediatrics – the child, the parents and carers, and ourselves.

This triad has received increased attention recently. The need for child centered care in respect of their engagement and involvement in their care. The need for positive communication with families; we remember the cases where parents haven’t acted as their child’s advocates but forget the vast majority of cases when they have. We so often let parents down when we should have been, not just listening to them, but honestly hearing what they were saying. And most recently the doctors themselves. An understanding of the importance of wellbeing and the shackles of rudeness. 

There is a fourth component, as well. One which perhaps will never get the attention it deserves because it isn’t a visceral part of our clinical care. It’s something we know exists but are quite willing to ignore. It’s something that perhaps has more impact on our practice than we would like to admit. It’s the variability in the actual care or treatment we provide or the fact that it might not be necessary at all.

When I became chair of PERUKI, Paediatric Emergency Research United Kingdom and Ireland, the international sibling of PREDICT and daughter of PERN I’d a personal vision that I would drive the organization forward in delivering ground-breaking new research highlighting novel interventions that would really make a difference to patients. What actually occurred is that I have realised that perhaps PERUKI has an even more important roll. One that does obviously include the need to develop, innovate and implement but one also that highlights where we could, and should do, better. It’s some examples of variation and the need for no treatment I would like to share. 

So this is an original selection of PERUKI members and those who helped us get PERUKI off the ground. I’d like a chance to pay particular tribute to Mark Lyttle at this point who has worked tirelessly at the outset to drive forward many early projects and is consistently named checked by our research partners for his ceaseless enthusiasm at collaborating and engaging. PERUKI took part in a prioritisation process published in 2015 with members putting forward their preferred research agendas and PERUKI publishing the top 20 via a Delphi process.

Number 4 on this list was: what is the best IV medication for Acute Asthma. PERUKI started on this work with essentially a two phase examination of the management of wheeze in March 2013. In the first phase a written questionnaire was undertaken. PERUKI sites responded as departments and 183 consultants responded individually on their wheeze management.

In study 99 (54.1%) use salbutamol as first-line intravenous therapy, 52(28.4%) magnesium sulfate and 27 (14.8%) aminophylline; 87 (47.5%) give these sequentially depending on response and 30 (16.4%) give them concurrently. Overall, 146 (79.8%) continue inhaled bronchodilators while on intravenous therapy.

When commencing on intravenous bronchodilators there were 10 different infusion rates with over 10-fold variation between the lowest and highest.

Everyone tends to have their little foibles about which treatment they prefer. And given the range of phenotypes and genotypes that exist in our wheezy cohort in can’t be the case that there is only going to be one best fit treatment for all patients. But a 10-fold difference probably pushes the bounds of flexibility.

What makes this more interesting is the second study. Also completed at the time (March 2013) was a prospective observational study. Data was screened from all patients presenting with wheeze and a detailed proforma completed for those who received intravenous therapies.Of 3238 children, 101 received intravenous therapies. Intravenous magnesium sulfate (MgSO4) was used in 67 (60.9%), salbutamol in 61 (55.5%) and aminophylline in 52 (47.3%) of cases. 

In 35 cases (31.8%), two drugs were used together, and in 18 cases (16.4%), all three drugs were administered.

More than half used salbutamol as the first-line intravenous agent, while fewer preferred magnesium sulfate or aminophylline, suggesting equipoise regarding which is most efficacious. To investigate this, participants were asked whether they would enrol patients to a randomised controlled trial allocating salbutamol, aminophylline or magnesium sulfate as the first-line intravenous agent, to which 148 (80.9%) responded positively. Asking clinicians who are regularly prescribing acute medications is vital for study design and subsequent implementation of study findings. With all due respect to respiratory paediatricians the question that they may be interested in, or want to explore, may well be completely out of keeping with the practice habits of emergency and acute paediatricians. PERUKI have welcomed increased engagement with our specialty colleagues in the last year and we hope we will reap the benefits of this. 

So a clear example of variation. I feel uncomfortable. Is there any reason to believe this variation has improved 6 years on? We have a challenge as the evidence base is not as strong as we would like. We look to Simon Craig and his work on developing asthma outcomes here – a PERN study I am very proud that PERUKI is part of. 

So what about where we think there is only a small amount of variation (a nationally agreed algorithm for example). DO we need to improve practice and CAN we improve practice? The EcLIPSE study was published a mere month ago and I am proud of the Don’t Forget the Bubbles team  for being part of the process of sharing this information widely. The Eclipse study compared levetiracetam and phenytoin in the treatment of status epilepticus. It was published on exactly the same day as the ConSEPT trial a similar study from our PREDICT friends. The EcLIPSE paper is available open access and there is a Don’t Forget the Bubbles summary. I also recommend the reviews by Justin Morgenstein and Casey Parker 

The primary outcome was time from randomisation to cessation of all visible signs of convulsive activity, defined as cessation of all continuous rhythmic clonic activity, as judged by the treating clinician.

Much debate has centred on what EcLIPSE and ConSEPT showed and at the heart of this is the difference between superiority and non-inferiority.

If these studies do nothing else it will to be to have spread the word about this construct. Because it is really important that people don’t glaze over or think because this terminology is used it’s someones else’s problem to analyse. I think this undue deference to academics probably perpetuates variation in care. I am not saying the theory is easy but neither is managing a sick neonate with congenital heart disease and we completely commit ourselves to doing that. 

Superiority trials aim to demonstrate that one intervention is better than other. The statistics, by convention, dictate that a difference between the interventions needs to be defined. In the case of EcLIPSE because phenytoin stopped status 60% of time and it was felt Levetiracetam may terminate seizures at a 75% rate the statistics calculated that 140 patients would be needed in each group. IF a difference exists this difference is likely to be a difference that is real and not by chance alone.

If they had wanted to show that levetiracetam was only 1% better then 1000s of patients would probably have been needed as if there was no difference by chance it would easily be possible that levetiracetam happened to be 1% better in that cohort of patients. 

A few interesting facts come out of EcLIPSE.

The first is that the while this wasn’t a perfect observational study – i.e not all patients presenting were recruited across a wide range of hospitals over 1400 patients were screened. This is a good cohort of children with seizures. About 10% of those who needed second line treatment for status were first presentations of afebrile convulsions and 5% were as a result of CNS infection.

Median time from randomisation to start of infusion was 11 min (IQR 8–15) for levetiracetam and 12 min (8–17) for phenytoin

But median time from randomisation to seizure cessation was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (IQR 24 to not assessable) in the phenytoin group.

These interventions take time! 

In EcLIPSE convulsive status epilepticus was terminated by levetiracetam in 106 (70%) participants, and by phenytoin in 86 (64%) participants. Therefore by the statistics LEVETIRACETAM is NOT better

Because the results are broadly the same it doesn’t mean they are equal – a non-inferiority study looks at two drugs and aims to calculate what is the minimum number of patients needed to be recruited into each intervention arm to demonstrate that one drug is not more than a certain % worse than another. By convention that number is normally 10%. The reason why 10% is important is that in EcLIPSE while it appears levetiracetam may have passed this test if the study had been designed as a non-inferiority in the ConSEPT study levetiracetam only terminated seizures (albeit as different end point) 50% of time; 10% worse than phenytoin. We don’t know yet what the meta-analysis may show us but this is planned.

A further suggestion is should we consider adding in levetiracetam with phenytoin; we could but that might delay some RSI intervention even further without overall benefit in seizure termination further. This is messy area where the complexity of clinical practice hints the required precision of research head on.

It might well be that you are happy for others to research novel drugs and techniques. You may well be content in supporting research through signposting or perhaps recruiting patients yourself. I would ask though that research itself is not scary. There is false divide between the ivory tower academic and jobbing clinician. Both these terms probably tribal and derogatory in their own way. We should all care about how effective our treatments are and where variability in practice is not in the patient’s interest. It is no more or less important than the three figures in Luke Fildes picture but perhaps it is less visible. 

Through PERUKI I’d like to champion this cause to make research feel more accessible. We are not doing research because we like to, we are doing it because we have to. 

A Simulcast journal club: Ben, Vic and Jesse at DFTB18

Cite this article as:
Team DFTB. A Simulcast journal club: Ben, Vic and Jesse at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19640

We were very privileged to be joined in Melbourne by the team from Simulcast. This piece of radio theatre was recorded in front of a live studio audience.

The team discussed, amongst others, these papers…

Ben Symon, Jesse Spurr and Victoria Brazil

Bearman M, Molloy E. Intellectual streaking: The value of teachers exposing minds (and hearts). Medical teacher. 2017 Dec 2;39(12):1284-5.

Ingrassia PL, Franc JM, Carenzo L. A novel simulation competition format as an effective instructional tool in post-graduate medical education. Advances in Simulation. 2018 Dec;3(1):17.

This talk was recorded live at DFTB18 in Melbourne, Australia. With the theme of ‘Science and Story‘ we pushed our speakers to step out of their comfort zones and consider why we do what we do. Caring for children is not just about acquiring the scientific knowhow but also about taking a look beyond a diagnosis or clinical conundrum at the patient and their families.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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ADC/DFTB Journal Club – May – Restrictive fluid boluses in shock

Cite this article as:
Charlotte Durand. ADC/DFTB Journal Club – May – Restrictive fluid boluses in shock, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19442

Rapid fluid rehydration is a key component in the management of paediatric patients presenting with septic shock. The 2009 American College of Critical Care Medicine – Paediatric Advanced Life Support (ACCM-PALS) guideline recommends boluses of 20mL/Kg up to 200mL/kg in the first hour. Results from the 2011 Fluid Expansion As Supportive Therapy (FEAST) trial showed an increased mortality in patients receiving bolus therapy in low-income countries, though it continues to be debated whether these findings are applicable to higher-income countries.

The Fluids in Shock (FiSh) pilot trial compared restricted bolus (10mL/kg) with the current recommendation (20mL/kg) to determine if a larger scale trial would be feasible in the UK. We discussed the paper in the May #DFTB_JC with expert input from author Dr David Inwald (@dlwanI)

Inwald DP, et al. Restricted fluid bolus volume in early septic shock: results of the Fluids in Shock pilot trial. Archives of Disease in Childhood 2019;104:426-431. https://adc.bmj.com/content/104/5/426

What was this study about?

The FiSh pilot was an open, multi-centre randomised controlled trial (RCT) involving 13 UK hospitals. 75 children were enrolled based on the presence of shock entry criteria (CRT ≥3s or systolic blood pressure <5th percentile for age) after an initial fluid bolus of 20mL/kg. Patients were randomised if they showed signs of shock after an initial 20mL/kg bolus to select for sicker patients. If they improved after the initial bolus they were excluded from the study group.

Boluses were delivered every 15mins (max 500mL of 10mL/kg group, or 1000mL for the 20mL/kg group) until patients’ signs of shock resolved.
79% of boluses were delivered per protocol in the 10 mL/kg arm and 55% in the 20 mL/kg arm. The volume of study bolus fluid after 4 hours was 44% lower in the 10 mL/kg group. There were no significant differences between the groups with regards to length of hospital stay, paediatric intensive care unit (PICU) admissions and PICU-free days at 30 days.

The twitter jury is still out on the reliability of capillary refill time, particularly in a resuscitation scenario. Dr Inwald gave an authors perspective on how they decided on shock criteria…

“It was difficult…in the end we went for hypotension OR prolonged CRT >=3s, in context of suspected infection – after 20 mL/kg. We didn’t use HR as too many confounders in ED. We were surprised that CRT was the main criterion in so many patients.” @Dlawni

Many had issues with inter-observer variability and confounding patient factors. Most participants emphasised not relying on CRT in isolation, but interpreting results in the context of other clinical features.

We’re in an LMIC – so, for a well nourished child, a LOT of emphasis. But – for severe malnutrition, they all have delayed CRT so no emphasis. I think even in HICs, in a case of poverty or neglect, I take it super seriously unless the child comes in looking scrawny. #DFTB_JC @mardi_steere

It’s a subjective measure, and needs to be kept in context of other signs of peripheral vasoconstriction. A CRT of 3s in a warm, perfusing child is likely either to be a) a sign I can’t count properly or b) this is a hot, annoyed child” #DFTB_JC @edd_broad

YOU HAVE TO WAIT 1 SECOND BEFORE SAYING “ONE”!!!” #DFTB_JC @apsmunro

I’ve found seconds to be an extraordinarily flexible measure of time, especially in the high stakes environment of a child potentially in circulatory collapse. See also 5 second ice bath dunks in SVT – unless someone is timing, it’s usually 2 seconds tops!” @edd_broad

It’s too subjective in my opinion. Plenty of evidence there is a lot of interobserver variability. I don’t put a lot of emphasis on CRT when resuscitating.” #DFTB_JC @davidking83

This trial contained an ‘embedded perspectives’ study which allowed researchers to collect qualitative information about the randomisation process from parents and carers. Trained site staff explained the process of RWPC and the nature of the intervention, which appeared to elicit support from parents. No parents refused consent during the study. The twittersphere vibe was one of support for this methodology, with the caveat that studies using RWPC must have sound ethical oversight to ensure interventions are of equal risk/potential benefit. The wonderful @kerry_woolfall spoke about this in more detail during her talk at #DFTB19

I think it’s the only way to get good quality research in time-critical topics. The lack of patients withdrawing is a good sign that this it is acceptable to families. It needs robust ethical oversight, though, to ensure true equipoise.” #DFTB_JC @DrSarahMcNab

It’s the only way we will get answers about dealing with critically ill children in the resuscitative phase of treatment. Not necessarily the future, I think that randomisation prior to inclusion carries more scientific weight, but a useful tool in the research arsenal” #DFTB_JC @edd_broad

Crucial for resus studies, but strong ethics board to make sure both interventions truly seem equal risk / potential benefit #DFTB_JC @mardi_steere

Dr Inwald explained the process of preparing for a trial involving RWPC…

RWPC is becoming more and more common in emergency care trials. We did a lot of work in our feasibility study to make sure our process had proper steer from parents and families and was also acceptable to staff. I was blessed with great co-investigators, particularly @kerry_woolfall who led the qualitative work. “#DFTB_JC @dlawnI

Adherence to the fluid bolus volume and timing was better in the 10mL/kg group, when compared to the 20mL/kg group. Authors proposed two principal reasons for this. Firstly, the technical difficulty in delivering the larger volume of fluid in 15mins; secondly, suggestions from the embedded perspectives study that clinicians favoured the 10mL/kg boluses.

Responses from journal club participants varied widely, with a range of responses and reasoning behind their preferred bolus volume. Interestingly, these responses reflected the lack of clinician equipoise identified in the study. Twitter is not the place to go for a consensus on a topic, but the variety of responses does highlight the disconnect between current guidelines and clinical practice across the world.

I use 20mL/kg in most kids needing a bolus, but I’ve noticed many people use 10mL/kg.” #DFTB_JC @DrSarahMcNab

I personally would never give 20ml/kg, I don’t see the need. Draw up 2x 10ml/kg, give one and reassess. Esp as most pt we bolus are babies and there’s always a cardiogenic shock hiding in there”. #DFTB_JC @apsmunro

It’s not my practice but it seems to have crept in. Have seen 5 mls/kg in DKA for example.” #DFTB_JC @davidking83

I give 20ml/kg if think they need a bolus with the exception of cardiac, DKA and trauma” @begley_roisin

Kidney docs say 10 Heart docs say 10 10 very easily repeatable Sketchy science for 20>10 I like 20/kg- always have – but #DFTB_JC has led to introspection for me” @pea88

I wouldn’t criticise anyone for using 20 mL/kg as a first bolus in an ED setting though. The evidence is weak both ways. FEAST was conducted in a setting without PICU so I think has limited applicability in a high income countries.” #DFTB_JC @Dlawni

Again a biased tweet from Kenya – but FEAST was impactful for us. So well nourished kids now we tend to 10-20/kg; malnourished no bolus – and early peripheral pressors (PIV or IO). Honestly, FEAST has helped us not be scared of pressors in the ED, which is good.” #DFTB_JC @mardi_steere

Though the workings of the trial were feasible, the lack of severe illness in the study population (due to reduced burden of vaccine-preventable disease) means a large scale trial could not be completed. What part of the study to we change? Some suggested altering the inclusion criteria to include all children needing a bolus

To change practice may need an earlier intervention study including the less sick patients (more reflective of true practice?). Randomise at first bolus to 10 vs 20ml/kg. Accept we can’t demonstrate diff in mortality, but that in itself may justify changing guidelines to 10ml/kg @apsmunro

Problem is that then there will too many well kids in the study who just get 1 bolus and go to the ward. All outcomes will be good in this population whatever you do, so it’s not useful to investigate. This is kind of what happened to an extent in FiSh… #DFTB_JC @dlawnI

We discussed how to look at sicker kids by using PICU as the study site rather than purely ED or non-PICU sites.

In rural/remote Australia we pick up a decent number of septic kids with @MedSTAR_SA – maybe we need to do a better job of studying multicentre aeromed retrieval platforms. @docjohncraven @AmyKKeir #DFTB_JC @mardi_steere

So probably a multicentre study looking at early resus in multidisciplinary children’s hospitals with integral PICU and ED. If you do a study in PICU it will be too late – all the resus fluid will have already been given and there will be no separation between the arms…#DFTB_JC @dlawnI

Multinational studies. Stratify according to access? FEAST is criticised as “not our population”, but really maybe its about access & timing, not genetics. #PedsICU based studies are risky as pre-diagnosed, pre-treated rather than de novo arrivals IMO #DFTB_JC @mardi_steere

Some suggested altered end points given how difficult it is to prove mortality difference – after all, when working with these children we are considering so much more in the risk/benefit analysis than just mortality.

I don’t think it will be feasible to show a difference in mortality in a high resource setting. There seemed to be a trend towards a difference in length of PICU stay and mechanical ventilation, though. #DFTB_JC @DrSarahMcNab

Difficult one – I think community acquired sepsis is becoming a rare disease in the post vaccine age so if a study was to be done in a high income setting it would need to include “all comers” with sepsis – including HCAI. #DFTB_JC @dlawnI

Inevitably, with any discussion on fluids and sepsis we must talk about pressors, too. There is always more research to be done!

We all need to talk more about peripheral pressors and peds sepsis bundle #ED implementation 🙂 #DFTB_JC @mardi_steere

This is more likely to be the future, as underlying issue isnt true hypovolaemia, its relative to vasodilation (in most sepsis groups). Pressers correct the deficit more truely than just pumping saline in (but we need some evidence to prove it!) #DFTB_JC @apsmunro

A big thank you to everyone who participated in the chat. If you missed out, please feel free to add your thoughts via the comments below. Keep an eye out on Twitter for the date + time of the next #DFTB_JC. We will see you there!

Awakening the FEAST: Why did fluid boluses kill?

Cite this article as:
Alasdair Munro. Awakening the FEAST: Why did fluid boluses kill?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19418

In paediatric medicine, it sometimes feels like we talk about sepsis more than anything else. We’ve all become familiar with the “sepsis bundles”, including a generous portion of intravenous fluid given as a rapid bolus in resuscitation.

This is why the FEAST trial blew everyone’s minds when it was published in 2011. This large RCT in East Africa of over 3000 children was stopped early when it demonstrated an increase in mortality for children given a fluid bolus of either 0.9% saline or 5% albumin instead of just maintenance fluids. It sparked huge controversy and various groups trying to explain away this effect with limited success. Guidelines however were not changed on the basis of this trial, because of concerns that it wasn’t applicable to a high resource setting, because the trial included children without measurement of blood pressure, and partially because no-one could come up with a good explanation for why this would be the case (see this breakdown in The Lancet). Why would giving a fluid bolus increase mortality in sepsis?

This is the question a new paper in The Lancet Respiratory Medicine tries to answer, using data from the FEAST trial (and others), and including members of the original FEAST team.

Levin M, Cunnington A, Wilson C, Nadel S, Lang H, Ninis N et al. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial. Lancet Respir Med. Epub June 2019 https://doi.org/10.1016/S2213-2600(19)30114-6

This study is a little complicated, but we can break it down to make it a bit easier to digest. Let’s start with the most important thing:

Research Question

We want to know why a fluid bolus increased mortality in FEAST.

To get to that, there are 2 questions asked in this study:

  1. Are changes in cardiovascular, neurological or respiratory function, or blood oxygen carrying capacity or biochemistry associated with adverse outcomes in children with sepsis?
  2. In the FEAST trial, were fluid boluses associated with changes in these parameters?

In order to address these 2 questions, the populations analysed were a mix from several studies of childhood sepsis, including:

3170 patients from the FEAST trial (children with sepsis from East Africa)

502 patients from the UK with meningococcal sepsis

448 from Malawi with cerebral malaria

61 children from South Africa with presumed sepsis/gastroenteritis (unpublished)

18,863 children attending a UK emergency department (unpublished)

Outcomes

The authors developed novel physiological scores for cardiovascular, neurological and respiratory function which could be assessed in a low/middle income setting. They didn’t use existing scores, as these are not single organ specific and require monitoring or tests which are not available in these settings, so could not be applied to the FEAST population

The scores were:

The cohorts other than FEAST were essentially just used to test their scoring system. They performed logistic regression to see if an increasing score (i.e. worsening on function) correlated with an “adverse outcome”. Basically testing if their score had any clinical relevance.

In the FEAST population, physiological scores and Hb, lactate, base excess, pH and electrolytes were measured at baseline (prior to any fluids) and then at several time points after fluid administration (either bolus or maintenance). Distributions of these scores were compared in the fluid bolus vs no bolus groups in FEAST to see if this could account for the increased mortality.

Other analyses

To cut a long study short – there are a huge number of different comparative analyses performed in this study. Feel free to spend days wading through the data (I know I will), but for now we’ll stick to the headlines which are the answers to our 2 big questions.

1.    Are changes in cardio, neuro or resp function, or blood oxygen carrying capacity or biochem associated with adverse outcomes?

The answer is yes.

In the FEAST trial, for every 10 units increase (worsening) in score, the odds ratio for death was; respiratory 1.09, neurological 1.26 and cardiovascular 1.09. So they’ve developed a new score, and looks like it tells is what we want.

In the other cohorts analysed, worsening of almost every physiological parameter was also associated with adverse outcomes (see pg 22 supp appendix)

2.    In the FEAST trial, were fluid boluses associated with changes in these parameters?

Yes they were.

Giving a fluid bolus increased (worsened) respiratory score by 3.45 at 1hr and neurological score by 2.64 at 1hr. These differences disappeared at 12h.

Fluid bolus decreased (improved) cardiovascular score by 2.17 at 1h. This difference disappeared at 12h.

Fluid bolus decreased Hb by 0.33g/dL at 8hrs

Fluid bolus did not change lactate

Fluid bolus decreased bicarbonate by 0.96mmol/L and decreased base excess by 1.41mEq/L

Additional points of interest

It made no difference if they received albumin or saline boluses, which is expected as there was no mortality difference either.

Higher volume fluid boluses (≥30mL/kg) were associated with worse respiratory and neurological scores at 4h then lower volume boluses, but high or low volume bolus made no difference in cardiovascular scores.

Significantly, in a post hoc principle component analysis (stay with me – this is not complicated I promise) – differences in physiological scores at 1h explain all the differences in mortality observed between bolus and no-bolus groups of the trial. The major determinants were neurological score, base excess and respiratory score. This is important as although differences between the groups were only apparent at 1h, this was enough to completely account for the differences in mortality.

There is some exciting cluster analysis (1. Mild derangement of scores, 2. Severe anaemia, high lactate and CV score, 3. High resp and neuro scores), but we will ignore this for now as the answer to our main questions didn’t differ among any of the clusters.

So how does a fluid bolus increase mortality in sepsis?

Whilst this question cannot be definitively answered through this study, the authors have presented a bioplausible explanation of their results. They have summarised it in an amazing picture, but if you like bullet points…

A fluid boluses causes:

  1. Haemodilution, causing anaemia, reducing O2 delivery and worsening metabolic acidosis
  2. Hyperchloraemia and bicarbonate dilution, worsening metabolic acidosis
  3. Worsening of respiratory function (partially through increased acidosis), causes decreased CO2 excretion, which both worsens metabolic acidosis and causes cerebral vasodilation, increasing intracranial pressure
  4. Cerebral oedema, causing raised intracranial pressure.

Limitations of the study

Should we all stop giving fluid boluses to children with sepsis now? Some limitations to consider from this study include:

  • This resource limited setting without intensive care may not be directly applicable to high income settings, as mechanical ventilation and neuro intensive care may be able to mitigate some of the adverse effects of bolus
  • Their scores are not independently validated and were not initially derived from the data
  • The influence of large volume fluid boluses may suffer from confounding by indication
  • Acid-base data was only available at 24hrs, by which time most deaths had occurred. Some analysis was performed using imputations.
  • Some of the statistics are almost impenetrable to us mere mortals

Conclusion

In the FEAST trial of children with sepsis in East Africa, a fluid bolus of either 0.9% saline or 5% albumin was associated with a worsening of respiratory and neurological function, anaemia and metabolic acidosis, which in turn was associated with increased mortality. There was a transient increase in cardiovascular function.

The implications of this according to the authors:

Particular care should be taken if considering giving fluid boluses to children with sepsis and respiratory or neurological compromise at presentation

Resuscitation with buffered solutions may be preferable in severely unwell children to avoid worsening of metabolic acidosis (trials in adults currently underway to assess this)

Where next?

As the authors state, it is unlikely ethical approval will be given for further trials of fluid boluses in a low/middle income setting following the increased mortality shown in FEAST. Conversely, trials in higher income countries are difficult because fluid boluses are seen as standard of care for sepsis, and as demonstrated recently in the FISH trial, sepsis has become so rare that trials of fluid management are difficult, even approaching unfeasible. We may find people become generally more cautious when implementing fluid bolus resuscitation as time goes on, perhaps with 10mL/kg boluses becoming preferable to the historically recommended 20mL/kg.

For further reading, check out the great accompanying editorial here, and check out references 3 – 14 in the paper for some of the heated controversy surrounding FEAST.