PEM Adventures Chapter 2

Cite this article as:
Dani Hall, Rachael Mitchell and Sarah Davies. PEM Adventures Chapter 2, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.30926

Are you ready for another PEM adventure? This time the stakes are a little higher. Join us on another journey (with an inbuilt time travel machine) as we manage Grace…

Teenager holding mobile phone

Meet Grace. Grace is a 15-year-old vegetarian environmental activist. She’s thrilled because she’s recently hit a TikTok following of 10,000 – social media is SO the way to spread the word.

She spent yesterday at an illegal climate strike rally outside parliament. Buoyed up on the adrenaline of a thrilling protest, she and some buddies went back to her friend, Zak’s house where they celebrated in style with vodka pops. But this morning, horrified by the fact Grace was impossible to wake, Zak called the emergency services.

Meanwhile, you’ve just fished a pea out of a child’s ear when the red phone rings. Hearing the pre-alert, you mobilise the team and prep a bay in resus. Minutes later, Grace is wheeled in with Zak in tow and she’s transferred to a trolley.

Whiteboard containing vital signs

Your SHO, Lucy, does a primary survey:

  • A: Tolerating an oropharyngeal airway. No stridor or stertor.
  • B: Self-ventilating in 15L O2 via a non-rebreathe mask. Respiratory rate is a bit raised but her chest is clear and she doesn’t have any other signs of respiratory distress.
  • C: Warm and well perfused, heart rate 68 with normal heart sounds and normal pulse volume. Blood pressure is 115/70 and capillary refill time is less than 2 seconds.
  • D: GCS 7, made up of M4, V2, E1. Pupils are size 3 bilaterally and normally reactive to light. Tone is generally low but reflexes are normal and plantars are down going.
  • E: No rashes, no bruises and Grace is currently afebrile.

Lucy gets Grace’s mum’s number from Zak and phones her to get a bit more information. Grace is a healthy adolescent with no significant past medical history. She’s not on any medications, is not allergic to anything and is fully vaccinated. She’s been completely well with no fever, cough, coryza, or any other symptoms. She did have a cold sore a few months ago – could that be relevant?

Grace’s parents, who had gone away for the first time since covid-lockdown lifted, are running to the train station to make their way back home.

Back in resus, you put in a cannula, and send off some bloods: FBC, U&E, LFT, CRP, blood culture and an alcohol level.

Her venous gas shows a pH of 7.47, pCO2 of 2.7, bicarb 14, lactate of 2.7 and normal glucose.

Blood gases showing respiratory alkalosis

That’s odd, you think to yourself, a respiratory alkalosis with some metabolic compensation. You pause for a second and work through your list of possible causes.

  1. Could this be a central cause of hyperventilation? A bleed? A tumour? A meningoencephalitis? You put up a request for CT brain. 
  2. Could this be a respiratory cause? Asthma? Pneumonia? Pneumothorax? Better get a chest x-ray too.
  3. Could this be sepsis? You prescribe ceftriaxone and add acyclovir. There was that coldsore after all…
  4. Pregnancy?
  5. Endocrine or hypermetabolic cause? Maybe DKA? No… her blood sugar’s normal. Or thyrotoxicosis?
  6. Maybe it’s something toxicological? You remember, from your undergraduate days, learning that salicylates cause a respiratory alkalosis.

You add a salicylate level, and paracetamol for good measure, add thyroid function and ask for a catheter urine for beta HCG and a tox screen.  

But her catheter urine doesn’t give you any extra clues. Grace’s urine beta-HCG is negative, her tox screen is negative and her dip is negative.

The resus nurse gently touches your elbow and quietly says, “Do you want to call the anaesthetist?

Good question, you think to yourself. Her GCS is 7 and she’s tolerating the oropharyngeal airway, but she’s breathing well for herself at the moment. What do you want to do?

There are some compelling arguments not to intubate; Grace is maintaining her airway and she’s obtunded and may have seizures – if you give her a paralysing agent as part of her RSI you’ll never be able to tell. Sure, if you really want to monitor for seizure activity, AND you’re in a a tertiary centre with a PICU with capability of CFM or EEG monitoring, you could keep arguing you can monitor for seizure activity while she’s intubated and ventilated, but it takes a while to set up, and time is of the essence.

So you make the brave decision not to intubate. 

You later decide it was less brave and more foolhardy. While Grace is in CT she drops her GCS further and then has a respiratory arrest, which quickly deteriorates into cardiac arrest. The scanner is a terrible place for CPR. While you’re trying to run an arrest on a narrow CT bed you wish you could go back in time and make that choice again. Luckily for you, the inbuilt PEM adventures time travel machine can do just that. In you hop and whizz back to resus.

Close the toggle and this time click on the ‘intubate’ choice.

There are some compelling arguments not to intubate; Grace is maintaining her airway and she’s obtunded and may have seizures – if you give her a paralysing agent as part of her RSI you’ll never be able to tell if she’s seizing. 

But there’s something niggling you… Grace is heading for a CT scan and the LAST thing you need is for her to arrest in the scanner.

And yes, it’s true, there is a risk you could miss a seizure if she was paralysed, but you can give her a long-lasting anticonvulsant to prevent seizures. 

So… you decide to follow your gut and make the decision to intubate.

Thankfully the anaesthetist is nifty with a tube and she’s already drawn up the RSI drugs – fentanyl, ketamine and rocuronium in a 1:1:1 ratio (that’s fentanyl 1mcg/kg, ketamine 1mg/kg and rocuronium 1mg/kg). She’s intubated without difficulty. 

Grace has bilateral equal breath sounds and a mobile chest x-ray shows the tube to be in a good position, with clear lung fields and normal heart size. You mentally cross respiratory causes of an alkalosis off your list.

You’re doing great.

The anaesthetist asks you, “How should I ventilate Grace? Should I match her raised respiratory rate?

That’s a good question, you think to yourself. What should you do?

This is a very good question and you’re not sure you know the answer. Grace is hyperventilating for some reason, and maybe mimicking this is the right thing to do…

But, you’re worried about her ultra low pCO2. At 2.7 it’s likely to be causing cerebral vasoconstriction and hypoperfusion. It’s time to start some simple, proactive neuroprotective measures.

On reflection, you decide it would be better to slow Grace’s breathing so resolutely you turn back to the anaesthetist and ask him to SLOW Grace’s respiratory rate to keep her end tidal CO2 tightly between 4.5 and 5; you want to prevent secondary brain injury.

He nods his assent, while tilting the head of the bed up to 30 degrees.

But, remembering a great DFTB post by Costas Kanaris, you know you can do more than that to neuroprotect. As well as maintaining normocapnia and nursing her at 30 degrees head in line, Grace needs strict normothermia and hypoxia should be avoided at all costs. She needs vigilant glucose monitoring, tight circulatory monitoring and support and an anticonvulsant to prevent seizures. 

Close the toggle and move on to the next part of the story.

You think this through. The alkalotic pH doesn’t matter quite so much, what’s really troubling you is Grace’s pCO2. With a pCO2 of 2.7, there’ll be huge amount of cerebral vasoconstriction and hypoperfusion. It’s time to start some simple, proactive neuroprotective measures.

Resolutely you turn back to the anaesthetist and ask him slow Grace’s respiratory rate to keep her end tidal CO2 tightly between 4.5 and 5; you want to prevent secondary brain injury and so now’s the time to start some neuroprotection.

He nods his assent, while tilting the head of the bed up to 30 degrees.

But, remembering a great DFTB post by Costas Kanaris, you know you can do more than that to neuroprotect. As well as maintaining normocapnia and nursing her at 30 degrees head in line, Grace needs strict normothermia and hypoxia should be avoided at all costs. She needs vigilant glucose monitoring, tight circulatory monitoring and support and an anticonvulsant to prevent seizures. 

Great choice! Close the toggle and move on to the next part of the story.

With fortuitous timing, CT ring down to say they’re ready for Grace.

Satisfied that A, B and C are all stable, you turn to take the brake off the trolley when Lucy, your SHO, asks, “But do we only want a plain non-contrast CT?

That’s a good question, you think to yourself. Is that all I want? What neuroimaging will you choose?

“Yes”, you say to Lucy. “A non-con CT is quick and will show us most tumours and bleeds. She can have an MRI later to get a bit more detail.” 

But,” your SHO counters, “a non-con CT won’t always detect an ischaemic stroke. Perhaps we should ask for a CTA too?

You remember a case from a few weeks ago, a little boy called Tomas. You’d bookmarked the RCPCH Stroke in Childhood guideline on your phone. You quickly bring it up and Lucy’s right, the guideline says to consider stroke in children with focal neurology, speech disturbance, focal seizures, severe headache, cerebellar signs… and unexplained decreased conscious level.

Smiling gratefully at Lucy you pick up the phone and ask the radiologist if you can add a CTA. They say yes.

Minutes later, Grace has her CT with CTA… but it’s normal. No abscess… no tumour… no bleed… and no stroke.

Well that’s good news for Grace, you think to yourself, but it doesn’t give you any much-needed clues.

Great work. Close the toggle and move onto the next part of the story.

You know what”, you say to your SHO, “let’s ask for a contrast-enhanced CT. It’s still quick and will give us a little more detail than a non-con CT.

But,” she counters, “do you think we should be considering stroke in our differential? Perhaps we should ask for a CTA too?

You remember a case from a few weeks ago, a little boy called Tomas. You’d bookmarked the RCPCH Stroke in Childhood guideline on your phone. You quickly bring it up and Lucy’s right, the guideline says to consider stroke in children with focal neurology, speech disturbance, focal seizures, severe headache, cerebellar signs… and unexplained decreased conscious level.

Smiling gratefully at Lucy you pick up the phone and ask the radiologist if you can add a CTA. They say yes.

Minutes later, Grace has her CT with CTA… but it’s normal. No abscess… no tumour… no bleed… and no stroke.

Well that’s good news for Grace, you think to yourself, but it doesn’t give you any much-needed clues.

Great work. Close the toggle and move onto the next part of the story.

You know what”, you say to your SHO, “let’s ask for a CT plus CTA. The CT will show us most tumours and bleeds and she can have an MRI later for a bit more detail, but we should consider stroke in our differential, and to detect that we need to add angiography to our CT.

You think back to a case from a few weeks ago, a little boy called Tomas. You’d read the RCPCH Stroke in Childhood guideline and remember that it says to consider stroke in children with focal neurology, speech disturbance, focal seizures, severe headache, cerebellar signs… and unexplained decreased conscious level.

Smiling gratefully at Lucy you pick up the phone and ask the radiologist if you can add a CTA. They say yes.

Minutes later, Grace has her CT with CTA… but it’s normal. No abscess… no tumour… no bleed… and no stroke.

Well that’s good news for Grace, you think to yourself, but it doesn’t give you any much-needed clues.

Great work. Close the toggle and move onto the next part of the story.

You haven’t ruled out infection. So, when you’re back down in resus, you ask Lucy if she’d like to do the LP.

Really? Is that safe with her low GCS?” she questions. 

What do you think? Should you LP?

It’s fine,” you reply, “she doesn’t have physiological signs of raised ICP: she’s not bradycardic or hypertensive, she’s not posturing and she didn’t have focal neurology. Plus, her CT doesn’t look like there’s cerebral oedema.

Feeling reassured, Lucy picks up the spinal needle and performs an LP. 

But it’s not your finest decision. Grace cones and arrests. 

Luckily for you and Grace, there’s an inbuilt time travel function in your PEM adventure and you return back to resus just as your SHO asks if it’s safe to LP Grace.

You have a strange feeling of déjà vu, while a little voice tells you that although a normal CT is usually reliable for ruling out raised intracranial pressure, this isn’t failsafe and it might be safer to defer the LP for when she’s a little more stable. You’ve already started the ceftriaxone and acyclovir, so this time you decide that the LP can wait until she’s a bit more stable and can have an MRI first. 

Thank goodness for that time machine! Close this toggle and move onto the next part of the story.

Lucy’s right. Although a normal CT is usually reliable for ruling out raised ICP, this isn’t failsafe and there’s no rush to get CSF now. You’ve already started ceftriaxone and acyclovir anyway. And when she’s a bit more stable she can have an MRI to check the LP’s safe. The LP can wait for now.

Great teamwork! Close the toggle and continue the next part of the story.

You’re still not sure what’s causing Grace’s low GCS though. Maybe the bloods will help. So you log in to the computer to check Grace’s results.

Results showing a mild transaminitis

Huh, you think to yourself. Grace’s FBC and CRP are normal; it’s sounding less and less like infection.

Her urea is low and her liver enzymes are raised, with a slightly prolonged INR.

Her salicylate and alcohol levels are undetectable. This isn’t feeling so toxicological anymore.

You mull this over with Lucy. Maybe this is a viral picture. There was that cold sore…

Just then Maureen, the ED cleaner, pops her head into the office. “Might this be of any use?” she asks. She’s holding the RCPCH Decreased Conscious level guideline.

You quickly flick through. Bloods… imaging… you’ve done pretty much everything it suggests. But then you take a closer look at the list of bloods it suggests. And there, in black and white, it says ammonia.

Of course!” you say out loud. “That would explain the respiratory alkalosis!

You draw off an ammonia sample, get it on ice and ask Raymond, the dashing porter, to run it down to the lab. You give the lab a ring so they can get the machine primed.

While you’re waiting for the result to come back, Zak comes running over. He’s just been looking in Grace’s backpack for her mobile and found a high protein Diet book. Apparently she’s been trying to lose weight for TikTok. Could it be relevant?

The cogs begin to whir… Hang on a minute… A high protein diet in a vegetarian environmental activist?

The lab phones with Grace’s ammonia level.

It’s over 500! And normal is less than 40.

It all falls into place. Selective vegetarian… Recent protein load… Raised transaminases… High ammonia… This is all beginning to sound a bit metabolic.

But what should you do about that ammonia? As far as you can see, the DeCon guidance only tells you to take it, not what you do when it comes back at over 10 times the upper limit of normal.

Just a sec,” says Lucy scrolling through her mobile phone, “The British Inherited Metabolic Disease Group have got this covered. They’ve produced a whole range of easy access emergency guidelines, including this one, for the management of an undiagnosed hyperammonaemia.”

It says, turn off protein catabolism by giving a 10% dextrose bolus followed by a dextrose infusion to provide an alternative energy source. If her glucose climbs, add insulin but don’t reduce the dextrose – otherwise, she’ll just start breaking down more protein. And, finally, mop up that ammonia with scavengers like phenylbutyrate and sodium benzoate.

The words ‘ammonia scavengers’ remind you of another post you read on Don’t Forget The Bubbles, about the different types of metabolic conditions, how they present and the various treatment strategies. You make a mental note to read it again later to remind yourself of the differences between an amino acid and organic acid.

Meanwhile, you hastily prescribe…

  •       A 2ml/kg bolus of 10% dextrose
  •       a dextrose infusion
  •       And those ammonia scavengers, sodium benzoate and sodium phenylacetate

Grace is subsequently diagnosed as having a urea cycle disorder. You’re amazed to discover that although most diagnoses are made in neonates, diagnoses are sometimes made in adolescents and adults presenting encephalopathic after a big protein load or when catabolic, such as after trauma, childbirth, major surgery, major haemorrhage, critical illness, rapid weight loss or simply after switching to a high protein diet. This is particularly true for ornithine transcarbamylase (OTC) deficiency, which although is X-linked, can present in symptomatic female OTC carriers. Little diagnostic clues include autoselective vegetarianism (that protein makes them feel a bit ‘ugh’) and subtle or behavioural difficulties from chronic low-level hyperammonaemia.

You bookmark a fantastic review article to read later and flick back through your undergraduate biochemistry textbook to remind yourself about urea cycle defects… and hastily close it again when you remember how little you knew even then, at the prime of your undergrad years.

Wow, what a shift. You pack up your stethoscope and head home, reflecting on your day as you walk to the bus stop.

Grace has taught you the importance of…

Reaching for the RCPCH DeCon guideline when looking after a child with an unexplained low GCS.

Not ever forgetting to send an ammonia in an encephalopathic child, young person or even adult; these tricksy urea cycle disorders can present in adulthood. If the ammonia comes back high, BIMDG have a handy guideline telling you exactly what to do.

And, remembering that a normal CT does not ALWAYS rule out raised ICP. In a child with low GCS, put away that LP needle and neuroprotect instead.

But what happened to Grace? Let’s jump in the time travel machine and find out…

Your epic diagnosis of a late presenting metabolic disorder was the talk of the ED. The RCPCH DeCon poster was put up in the ED staff room and from that point onwards, everyone remembered to check an ammonia in a patient presenting with an unexplained low GCS. 

Lucy was nominated as employee of the month. This shift was a pivotal moment in her career as she decided PEM was her vocation.

The ammonia scavengers did the trick and Grace made a full recovery.

Grace focussed her efforts on reducing plastic waste in hospital and successfully petitioned for the introduction of plastic-free PPE, reducing plastic waste during the COVID-19 pandemic by an incredible 275%.

She hit 3 million TikTok followers (and you’re one of them).

This PEM adventure wouldn’t have been possible without some help from some amazing people. Thank you to Roshni Vara, Consultant in Paediatric Inherited Metabolic Disease at the Evelina London, Costas Kanaris, PICU and retrieval consultant at the Royal Manchester Children’s Hospital and Jon Lillie, PICU and retrieval consultant at the Evelina London Children’s Hospital.

Here are some of their wise words of advice…

As Costas says in The N of 1 matters, we’ve outlined our take on Grace’s case and how we’d manage her in our own resus bays. Medicine’s not always so clear cut and there are often different approaches to the same problem, but this is our consensus on minimising risk using, as Costas says, a rational, evidence-based and pharmacologically prudent approach (I love that phrase Costas!)

Should we intubate Grace?

Grace is self-ventilating but the fact that she is tolerating an oropharyngeal airway means some of her airway reflexes have gone. Scanning a child with a GCS of 8 or less, without securing the airway, puts them at risk. If they vomit, they aspirate. If they stop breathing and arrest in the scanner, the CT room is one of the least fun places to run an arrest, perhaps second only to an elevator. Are there any counter-arguments? Yes, and they’re soft.  One is “this patient is encephalopathic/obtunded and may have seizures; if the child starts fitting we won’t be able to tell as they’ll be paralysed”.  Costas says he usually stands his ground and says that if someone is worried about seizures then the child can be given a long-acting antiepileptic. Levetiracetam is his preference, although phenytoin would work just as well unless there’s suspicion of an overdose of an arrhythmogenic agent. The last thing you need is to tip this child into an arrhythmia.

When should a lumbar puncture be performed in a child with a decreased conscious level?

CT is a useful tool for ruling out raised intracranial pressure before proceeding to lumbar puncture. And we’d agree. But Grace has a low GCS and this changes the picture.

If we take a look at the full RCPCH DeCon guideline it dedicates a whole section to answering the question about LP in decreased conscious level. So, let’s start there.

The DeCon guideline advises a lumbar puncture if your differentials are viral encephalitis or tuberculous meningitis and advises that we consider lumbar puncture when our differentials are bacterial meningitis, sepsis, or the cause of the low GCS is not known. This is cloaked with the phrase “when no acute contraindications exist” and this is key. So what are those contraindications?

  • Signs of raised intracranial pressure: dilated pupil(s), abnormal pupil reaction to light, bradycardia, hypertension or abnormal breathing pattern.
  • A GCS equal to or less than 8, or a deteriorating GCS
  • Focal neurology
  • A seizure lasting more than 10 minutes with a GCS less than 13
  • Shock or clinical evidence of meningococcal disease
  • CT or MRI suggesting obstruction of the CSF pathways by blood, pus, tumour or coning.

What’s the evidence? Well, it’s mostly been derived by expert opinion, and there aren’t many people who’d dispute them.

But what about when you have a normal CT? The radiologists can look for midline shift and for signs of impending herniation by assessing the position of the cerebellar tonsils. So, surely that can rule out raised ICP, allowing an LP to be done?

The DeCon guideline quotes a study published in 2000 that showed that in 124 CT scans from 65 children with traumatic brain injury, CT had an excellent sensitivity of detecting raised ICP of 99.1%, with a specificity of 78.1%. But, a 2019 revision to the guideline says that no further evidence about the sensitivity or specificity of CT in detecting raised ICP in children has been found. None. Although the sensitivity in the one quoted study was very high, it was felt that one study, in children with traumatic brain injury, could not be extrapolated to all children with a decreased conscious level. And so the guideline states that a normal CT scan does not exclude raised ICP. If other contraindications are present, don’t use a normal CT to justify LP.

What does this mean in practice? Well, in a child with a GCS of 8 or less, like Grace, there’s no rush to do an LP. It’s unlikely to change your management acutely in the ED. Her infection can be treated empirically and once she’s more stable, and you have more information including, potentially, an MRI, she can then have an LP for PCR.

What neuroimaging should we do?

That’s a good question, answered beautifully by an article by Hayes et al, published in 2018. Although this article focuses on neuroimaging for headaches, it has a great section on when you might choose each type of scan.

We’d all agree that the ideal imaging to look for a brain tumour is an MRI. It gives excellent detail about the brain tissue as well as other intracranial soft tissues and the extra-axial CSF spaces.

But, if you want a quick answer, or your access to MR is difficult, a non-contrast CT can be performed easily from the ED. If there’s no possibility of a later MR, then contrast-enhanced CT might be better as it gives more detail, but it’s more radiation – this is one for discussion with the radiologist.

CT is very sensitive in detecting blood, and it can be done quickly, in an emergent setting from the ED. So, in children with thunderclap headache, when you want to exclude subarachnoid hemorrhage, a non-contrast CT will be your first choice scan. If blood is detected, then add in arterial imaging: CT or MR angiography (CTA or MRA). Contrast is injected and images taken in the arterial phase.

CTA or MRA are also useful in the investigation of suspected stroke. In practice, you need an answer fast, particularly if the child’s within the thrombolysis window and could be a candidate if there’s evidence of ischaemic stroke, so a CTA is a more practical scan. The CT component looks for blood or large areas of parenchymal infarct, while the angiography looks for filling defects in the arteries that could indicate a thrombus.

If you’re looking for intracranial extension of infection, such as from an orbital cellulitis, mastoiditis or a brain abscess, then a contrast-enhanced CT will highlight suppurative collections.

And if you suspect a venous sinus thrombosis, such as in children with coagulopathies, sickle cell disease, infective spread from meningitis / mastoiditis / sinusitis, or secondary to dehydration or renal failure? Then you need to look at the venous spaces. CT or MR venography (CTV or MRV), when contrast is injected and images obtained in the venous phase, will give you the answers you need.

And what ARE the causes of a respiratory alkalosis?

There are a few! Here are the main ones:

  • Central: brain tumours, meningoencephalitis; stroke
  • Respiratory: asthma, pneumonia, pneumothorax, PE
  • Sepsis
  • Pregnancy
  • Endocrine and hypermetabolic cause: DKA, thyrotoxicosis
  • Toxicology: salicylates 
  • Hyperammonemia: liver and metabolic disorders 
infographic of causes of respiratory alklosis

We would LOVE your feedback about these DFTB PEM adventures so if you can spare a minute, please complete our survey at www.tiny.cc/DFTBpemadventure or use your smartphone to let the QR code take you straight there. We timed ourselves completing it and it takes less than a minute. Thank you.

Select references

The management of children and young people with an acute decrease in conscious level. A nationally developed evidence-based guideline for practitioners. RCPCH. 2015 update, with 2019 revisions. Management of children and young people with an acute decrease in conscious level – Clinical guideline | RCPCH

Undiagnosed Hyperammonaemia. Diagnosis and Immediate Management. British Inherited Metabolic Disease Group. Last reviewed 2017. The major causes are as follows (bimdg.org.uk)

Hirsch, W., Beck, R., Behrmann, C. et al. Reliability of cranial CT versus intracerebral pressure measurement for the evaluation of generalised cerebral oedema in children. Pediatric Radiology 30, 439–443 (2000). https://doi.org/10.1007/s002470000255

Expert Panel on Pediatric Imaging:, Hayes LL, Palasis S, Bartel TB, Booth TN, Iyer RS, Jones JY, Kadom N, Milla SS, Myseros JS, Pakalnis A, Partap S, Robertson RL, Ryan ME, Saigal G, Soares BP, Tekes A, Karmazyn BK. ACR Appropriateness Criteria® Headache-Child. J Am Coll Radiol. 2018 May;15(5S):S78-S90. doi: 10.1016/j.jacr.2018.03.017. PMID: 29724429.

Mitani H, Mochizuki T, Otani N, Tanaka H, Ishimatsu S. Ornithine transcarbamylase deficiency that developed at the age of 19 years with acute brain edema. Acute Med Surg. 2016;3(4):419-423. doi:10.1002/ams2.214

Summar ML, Barr F, Dawling S, Smith W, Lee B, Singh RH, Rhead WJ, Sniderman King L, Christman BW. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin. 2005 Oct;21(4 Suppl):S1-8. doi: 10.1016/j.ccc.2005.05.002. PMID: 16227111.

Kanaris C, Ghosh A, Partington CG389(P) A case for early ammonia testing in all encephalopathic patients: female patients with x-linked ornithine transcarbamylase deficiency. Archives of Disease in Childhood 2015;100:A158-A159. http://dx.doi.org/10.1136/archdischild-2015-308599.343

Summar, Marshall. (2005). Presentation and management of urea cycle disorders outside the newborn period. Critical Care Clinics. 21. IX-IX. 10.1016/j.jccc.2005.08.004.

Bubble Wrap PLUS – October/November 2020

Cite this article as:
Grace Leo. Bubble Wrap PLUS – October/November 2020, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.30866

Can’t get enough of Bubble Wrap? The Bubble Wrap Plus is a monthly paediatric journal club reading list from Anke Raaijmakers working with Professor Jaan Toelen & his team of the University Hospitals in Leuven. This comprehensive list is developed from 34 journals, including major and subspecialty paediatric journals. We suggest this list can help you discover relevant or interesting articles for your local journal club or simply help you to keep a finger on the pulse of paediatric research.

This month’s list features answers to intriguing questions such as: ‘How do children respond to masked paediatricians?’, ‘Are the youngest children in a classroom at increased risk of being medicated for ADHD?’, ‘Does neonatal paracetamol treatment lead to problems later in life?’, ‘Are probiotics useful for treating IBS?’ and ‘Is digital media exposure early in life associated with autism?’.

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

1.Reviews and opinion articles

Multisystem Inflammatory Syndrome in Children and SARS-CoV-2 Serology.

Zeichner SL, et al. Pediatrics. 2020 Sep 24:e2020032888.

Update on congenital cytomegalovirus infection: Prenatal prevention, newborn diagnosis, and management.

Barton M, et al. Paediatr Child Health. 2020 Sep 16;25(6):395-396.

Do probiotics in pregnancy reduce the risk of group B streptococcal colonisation?

Jois RS, et al. J Paediatr Child Health. 2020 Sep;56(9):1468-1472.

Trajectories of Lung Function in Infants and Children: Setting a Course for Lifelong Lung Health.

Jordan BK, et al. Pediatrics. 2020 Sep 16:e20200417.

Principles of immunisation in children with solid organ transplant.

Kelgeri C, et al. Arch Dis Child. 2020 Sep 16:archdischild-2020-319822

What time interval is needed between the administration of live attenuated vaccines?

Zimmermann P, et al. Arch Dis Child. 2020 Sep 8:archdischild-2020-320091.

For Victims of Fatal Child Abuse, Who Has the Right to Consent to Organ Donation?

Deutsch SA, et al. Pediatrics. 2020 Sep;146(3):e20200662.

Advocating for Children During the COVID-19 School Closures.

Masonbrink AR, et al. Pediatrics. 2020 Sep;146(3):e20201440.

2. Original clinical studies

Coronavirus infection in neonates: a systematic review.

Trevisanuto D, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Sep 17:fetalneonatal-2020-319837.

Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.

Viner RM, et al. JAMA Pediatr. 2020 Sep 25.

Frequency of Children vs Adults Carrying Severe Acute Respiratory Syndrome Coronavirus 2 Asymptomatically.

Milani GP, et al. JAMA Pediatr. 2020 Sep 14.

Masked paediatricians during the COVID-19 pandemic and communication with children.

Shack AR, et al. J Paediatr Child Health. 2020 Sep;56(9):1475-1476.

Possible Coronavirus Disease 2019 Pandemic and Pregnancy: Vertical Transmission Is Not Excluded.

Marzollo R, et al. Pediatr Infect Dis J. 2020 Sep;39(9):e261-e262.

Probable Vertical Transmission of SARS-CoV-2 Infection.

Demirjian A, et al. Pediatr Infect Dis J. 2020 Sep;39(9):e257-e260.

Prepubertal gynecomastia is not always idiopathic: case series and review of the literature.

Laimon W, et al. Eur J Pediatr. 2020 Sep 25.

Reducing Antibiotic Prescribing in Primary Care for Respiratory Illness.

Kronman MP, et al. Pediatrics. 2020 Sep;146(3):e20200038

Surfactant use in late preterm infants: a survey among Belgian neonatologists.

Cornette L, et al. Eur J Pediatr. 2020 Sep 24.

Magnet Ingestions in Children Presenting to Emergency Departments in the United States 2009-2019: A Problem in Flux.

Reeves PT, et al. J Pediatr Gastroenterol Nutr. 2020 Sep 22.

E-cigarette or Vaping-Associated Acute Lung Injury and Hemophagocytic Lymphohistiocytosis.

Derespina KR, et al. Pediatrics. 2020 Sep 23:e20193664.

Resuscitation of non-vigorous neonates born through meconium-stained amniotic fluid: post policy change impact analysis.

Oommen VI, et al..Arch Dis Child Fetal Neonatal Ed. 2020 Sep 22:fetalneonatal-2020-319771.

Value of serial echocardiography in diagnosing Kawasaki’s disease.

Hörl M, et al. Eur J Pediatr. 2020 Sep 21.

Children’s Relative Age and ADHD Medication Use: A Finnish Population-Based Study.

Vuori M, et al. Pediatrics. 2020 Sep 21:e20194046.

Brain Morphology Associated With Obsessive-Compulsive Symptoms In 2,551 Children From the General Population.

Weeland CJ, et al..J Am Acad Child Adolesc Psychiatry. 2020 Sep 16:S0890-8567(20)31837-2.

The biological and social determinants of childhood obesity: comparison of two cohorts 50 years apart.

Robinson N, et al. J Pediatr. 2020 Sep 16:S0022-3476(20)31164-1.

Lung ultrasound features predict admission to the neonatal intensive care unit in infants with transient neonatal tachypnoea or respiratory distress syndrome born by caesarean section.

Poerio A, et al. Eur J Pediatr. 2020 Sep 19.

Clinical and Epidemiologic Characteristics of Pertussis in Hospitalized Children: A Prospective and Standardized Long-term Surveillance Study.

Zumstein J, et al. Pediatr Infect Dis J. 2020 Sep 16.

Long-term Cognitive, Psychological, and Health Outcomes Associated With Child Abuse and Neglect.

Strathearn L, et al. Pediatrics. 2020 Sep 17:e20200438

Childhood Adversity and Health After Physical Abuse.

Campbell KA, et al. Pediatrics. 2020 Sep 16:e20200638.

Intravenous paracetamol for neonates: long-term diseases not escalated during 5 years of follow-up.

Juujärvi S, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Sep 17:fetalneonatal-2020-319069.

Use of probiotics in the treatment of functional abdominal pain in children-systematic review and meta-analysis.

Trivić I, et al. Eur J Pediatr. 2020 Sep 17.

Preliminary study on the feasibility of a two-stage screening strategy for otitis media with effusion in children.

Yang J, et al. J Paediatr Child Health. 2020 Sep 17.

Longitudinal Changes in Early Nasal Microbiota and the Risk of Childhood Asthma.

Toivonen L, et al. Pediatrics. 2020 Sep 15:e20200421

Where are they now? An autism follow-up study.

McDonald J, et al. J Paediatr Child Health. 2020 Sep 15.

Use of procalcitonin and C-reactive protein in the diagnosis of bacterial infection in infants with severe bronchiolitis.

Alejandre C, et al. Eur J Pediatr. 2020 Sep 14.

Association Between Congenital Cytomegalovirus and the Prevalence at Birth of Microcephaly in the United States.

Messinger CJ, et al. JAMA Pediatr. 2020 Sep 14.

Human Herpes Virus 6 Detection in Children With Suspected Central Nervous System Infection.

Cosme I, et al. Pediatr Infect Dis J. 2020 Sep 7

Urine collection methods and dipstick testing in non-toilet-trained children.

Diviney J, et al. Pediatr Nephrol. 2020 Sep 12

Reassessing the Use of Proton Pump Inhibitors and Histamine-2 Antagonists in Critically Ill Children: A Systematic Review and Meta-Analysis.

Jie Yao DW, et al. J Pediatr. 2020 Sep 8:S0022-3476(20)31139-2

Early Neurodevelopmental Trajectories for Autism Spectrum Disorder in Children Born Very Preterm.

Chen LW, et al. Pediatrics. 2020 Sep 8:e20200297

Childhood Obesity is Associated with Poor Academic Skills and Coping Mechanisms.

Gill N, et al. J Pediatr. 2020 Sep 4:S0022-3476(20)31129-X.

Sounding the Alarm on Sleep: A Negative Association Between Inadequate Sleep and Flourishing.

Tsao HS, et al. J Pediatr. 2020 Sep 2:S0022-3476(20)31116-1.

Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial.

Dani C, et al. Eur J Pediatr. 2020 Sep 4.

Multidisciplinary approach to paediatric aerodigestive disorders: A single-centre longitudinal observational study.

Fuladi A, et al. J Paediatr Child Health. 2020 Sep 4

Did children ‘stay safe’? Evaluation of burns presentations to a children’s emergency department during the period of COVID-19 school closures.

Mann JA, et al. Arch Dis Child. 2020 Sep 3:archdischild-2020-320015.

Increased IgE-Mediated Food Allergy With Food Protein-Induced Allergic Proctocolitis.

Martin VM, et al. Pediatrics. 2020 Sep;146(3):e20200202

Machine Learning To Predict Serious Bacterial Infections in Young Febrile Infants.

Ramgopal S, et al. Pediatrics. 2020 Sep;146(3):e20194096.

Machine Learning and Clinical Prediction Rules: A Perfect Match?

Chamberlain JM, et al. Pediatrics. 2020 Sep;146(3):e2020012203.

Parent Involvement in Adolescent Obesity Treatment: A Systematic Review.

Bean MK, et al. Pediatrics. 2020 Sep;146(3):e20193315

Social/digital media exposure early in life associated with autistic symptoms.

Chonchaiya W. J Pediatr. 2020 Sep;224:179-183

What is the effectiveness and safety of different interventions in the management of drooling in children with cerebral palsy?

Khajuria S, et al. Arch Dis Child. 2020 Sep;105(9):906-910.

Varicella Zoster Reactivation Causing Aseptic Meningitis in Healthy Adolescents: A Case Series And Review Of The Literature.

Barry R, et al. Pediatr Infect Dis J. 2020 Sep;39(9):e278-e282

How Much Is Too Much? Examining the Relationship Between Digital Screen Engagement and Psychosocial Functioning in a Confirmatory Cohort Study.

Przybylski AK, et al. J Am Acad Child Adolesc Psychiatry. 2020 Sep;59(9):1080-1088.

4. Case reports

Penny Ingestion: Can We Really Manage Expectantly?

Krasaelap A, et al. J Pediatr Gastroenterol Nutr. 2020 Sep;71(3):e101-e102

Do not trust your gut: A rare cause of oedema in a 3-year-old.

Cilento SV, et al. J Paediatr Child Health. 2020 Sep 11

Rectal prolapse but it is not just a rectal prolapse.

Al Mughaizwi T, et al. J Paediatr Child Health. 2020 Sep 5.

Spontaneous Pneumomediastinum: Unusual Cause of Sore Throat.

Kumai T, et al. J Pediatr. 2020 Sep;224:176-177.

A Persistent “Pimple” in a 5-Year-Old Girl.

Bell KA, et al. J Pediatr. 2020 Sep;224:172-173.

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

Gastroenteritis

Cite this article as:
Angharad Griffiths. Gastroenteritis, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28790

Conor is a 10 kg, 13 month-old boy who’s presented to the ED with a 24-hour history of diarrhoea and vomiting.  He has had 5 episodes of non-bloody, non-bilious vomits. Since waking up this morning has two episodes of loose/watery non-bloody malodorous stools. They have not ‘flooded’ the nappy but were quite large.  He is taking sips of fluid (mixtures of water, milk, and juice being offered) and has only eaten half a digestive biscuit so far today.  He has had a fairly large wet nappy last night, but not since, though it’s now difficult to tell as his last nappy was dirty.  He is alert and looking around while being carried but is upset on leaving his mother’s arms.  He cries with tears, has a normal heart rate but his mother is worried about his dry lips.  She was told by a healthcare worker neighbour that he will “need a drip”. CRT, HR, and BP are normal.  His temperature is 37.8.  His nappy is dry and has been on for 3 hours now.  His capillary glucose measurement is 3.2.  You decide he’s probably mildly dehydrated.

Introduction

Gastroenteritis (GE) is the presence or diarrhoea or vomiting (or both) that may or may not be accompanied by fever, abdominal pain and anorexia.  Diarrhoea is the passage of excessively liquidy or frequent stools with liquid high water content.  Although often felt to be a common minor illness presentation, it is a major cause of childhood mortality and morbidity, causing millions of deaths worldwide in children in low and middle-income countries; of all child deaths from gastroenteritis 78% occur in Africa and South-East Asia. 

Gastroenteritis accounts for a huge proportion of GP and ED presentations. In Europe, acute gastroenteritis the third commonest cause of hospital admission, accounting for between 4-17% of admissions.  In Australia, gastroenteritis caused by rotavirus alone accounts for 115,000 GP visits, 22,000 ED visits and 10,000 hospital admissions a year, with an estimated cost of 30m Australian Dollars (£12m, €18m).  In the UK, 20% of GP consultations in the under 5’s are for GE.

It is imperative that the child with gastroenteritis is differentiated from more sinister causes of vomiting.  The presence of diarrhoea is reassuring but doesn’t exclude other intra-abdominal causes.  The same can be said for pain out of proportion with gastroenteritis, distension, peritoneal signs or localised tenderness.

Most cases are not associated with complications but when complications do occur, the commonest are electrolyte disturbance and metabolic acidosis.  Supplementary fluids through oral or intravenous routes are the most effective way to avoid these complications.

Gastroenteritis in low and middle-income countries can present differently, has different aetiologies, is often managed differently, and is a larger burden to healthcare systems in general than in high-income countries.  This post will focus on gastroenteritis in high-income countries. For more information about comparisons of guidelines across the world; Vecchio et al (2016) is an interesting read.

This is not meant to provide a clinical practice guideline; rather an overview of the illness.  Many (if not all!) paediatric emergency departments or general paediatric units have their own guidelines.

Pathophysiology

Worldwide, the commonest causes are viral pathogens, most commonly rotaviruses and noroviruses.  Viral infections cause damage to the small bowel enterocytes with resultant low-grade fevers and watery diarrhoea – classically without blood.  Rotavirus strains are seasonal and vary within different geographical areas.  The peak age for these infections is between 6 months and 2 years.  Children with poor nutrition are at higher risk of acquiring gastroenteritis and developing dehydration and complications.

Children with bacterial gastroenteritis are more likely to have bloody stool.
Escherichia coli and Shigella dysenteriae can be complicated by haemolytic uraemic syndrome (HUS).  This is an acute onset, microangiopathic haemolytic anaemia, thrombocytopaenia, acute renal impairment and multisystem involvement.  (Just to confuse things, HUS can present in the absence of bloody diarrhoea.)

Pathogens can be generalised into four groups:

  • Viral (70% of cases): Rotavirus, Norovirus, Adenovirus, Enterovirus
  • Bacterial (10-20% of cases): Campylobacter jejuni, Salmonella spp, Escherichia coli, Shigella spp, Yersinia enterocolitica.
  • Protozoa (unusual, accounting for <10%): Cryptosporidium, Giardia lamblia, Entamoeba histolytica
  • Helminths (very unusual): Strongyloides stercoralis

Transmission

Pathogens are spread mainly via the faeco-oral route, acquired by ingesting contaminated food or drink.  Water may be contaminated with bacteria, viruses, or protozoa. Undercooked (or inappropriately stored/cooked) meats and seafood are common culprits of bacterial pathogens.  Bacterial contaminants can produce toxins (e.g. Bacillus cereus in re-warmed rice or Staphylococcus aureus in ice-cream).

Pathogens causing gastroenteritis can also be transmitted without the patient being symptomatic.

Assessment

Gastroenteritis is a clinical diagnosis.  Enquire about sick/infectious contacts and potential sources (recent travel, food).  Enquire about the frequency of symptoms and intake of fluids.  Note the frequency of urination.  Note other things that may cause diarrhoea e.g. recent use of enteral antibiotics or chronic constipation with overflow diarrhoea the presenting feature. 

In the presence of signs such as high fever, long duration of symptoms, severe abdominal pain or bilious vomiting; review the diagnosis and do not immediately label as gastroenteritis.

Oral hydration fluids

Most children are not dehydrated and can tolerate oral fluids and so can be managed at home.  Take a look at Nikki Abela’s DFTB19 talk on top tips for a high yield dehydration assessment.

When children are only mildly to moderately dehydrated, as a general rule they can be treated with oral / enteral rehydration with low osmolality oral rehydration solution (ORS).  Worldwide, ORS is recognised as first line therapy and treating mild to moderate dehydration with enteral rehydration is supported by the WHO, European Society for Paediatric Gastroenterology and the American Academy of Paediatrics. The WHO recommends a low osmolality (hypo-osmolar) solution, usually containing sodium, potassium, chloride, carbohydrate (glucose) and a base.  Low osmolarity solutions reduce the need for IV fluids, reduce stool output and reduce vomiting frequency.

But… a major limitation to the use of ORS is its taste – and this is where apple juice comes in. For minimally dehydrated patients, half-strength apple juice is associated with fewer treatment failures compared to ORS and could suit as a more palatable alternative.  Take a look at a sweet summary (pun intended!) of the “apple juice trial”.

Breastfeeding should continue and a child can be supplemented with ORS if this is needed.  Children can go back to a normal diet after the illness has passed.

Enteral (oral / NG) versus IV hydration

Most studies show that enteral rehydration with ORS is just as effective as IV hydration in mild to moderate dehydration with a 2006 Cochrane analysis concluding that enteral rehydration is as effective if not better than IV rehydration with fewer adverse events and a shorter hospital stay.  It is also less invasive (even with NG placement) and anecdotally satisfaction is greater amongst parents.  It is very safe.

Enteral rehydration only fails in approximately 1 in 20-25 children.

Barriers to oral rehydration include unfamiliarity with the benefits, misconception that it takes longer than IV therapy, and that it has a high failure rate.

Contraindications to enteral rehydration include haemodynamic instability, abdominal distension, concern over ileus, absent bowel sounds, or impaired airway reflexes.

IV therapy is more invasive and involves placing and maintaining IV access.  There are also iatrogenic complications including electrolyte disturbance should inappropriate fluids / composition / volume / rate be used. 

But… in severely dehydrated children, put away the ORS and apple juice. They will need IV rehydration as first line.

Antiemetics

How can we support enteral fluids? Well, children who receive Ondansetron are less likely to vomit, have greater oral intake and are less likely to require IV hydration.  A Cochrane review demonstrates that Ondansetron also increases the proportion of children who stop vomiting when compared to placebo [RR1.4] and reduces the proportion of children needing IV therapy (and therefore admission rate) [RR 0.41].  Median length of stay is also shorter in the ED. 

Reported side effects are rare with very few reported side effects other than a few cases of increased frequency of diarrhoea.

Antiemetics alleviate vomiting by acting on the ChemoReceptor Trigger Zone and vomiting centre.  Ondansetron is a 5HT3 receptor antagonist.  This class of antiemetics have fewer adverse effects (than dopamine antagonists, anticholinergics, antihistamines and corticosteroids) and can be safely used in children.  The NICE guideline discusses its off-licence use (at time of publication it’s licence was for post-operative nausea and vomiting and chemotherapy induced vomiting).

Ondansetron prolongs the QT interval.  Recommendations are it should be avoided in those with long QT and should be used in caution where there may be electrolyte imbalance (severe dehydration) or on other QT-prolonging medication.

Ondansetron is relatively cheap  £1.71 for 10 4mg tablets and is available in oro-dispersible form (though these are much more expensive at £36 for 10x4mg tablets) and liquid (£36.82 for 40mg [50ml] bottle).

Probiotics

An ESPGHAN working group position paper on the use of probiotics in acute paediatric gastroenteritis concludes that:

  • Effects seen in clinical trial are probiotic strain specific (this makes ‘trial-life’ difficult to replicate in ‘real-life’).
  • A lack of evidence now doesn’t mean that there won’t be evidence sometime in the future. 
  • Safety profile of certain strains cannot be extrapolated to other strains.
  • Studies that report benefits in certain doses in certain settings have insufficient evidence to support a health benefit at lower doses and different setting.

…the jury’s still out.

Other therapies

Antibiotics and anti-diarrhoeal agents aren’t routinely recommended in the management of paediatric gastroenteritis.

For gastroenteritis in high income countries, the WHO does not recommend adding zinc to a treatment regimen (it is for gastroenteritis in low and middle income countries). 

Investigations

Routine lab testing in mild and moderate gastroenteritis is of little value in these patients and should be avoided unless clinically indicated.

This goes for stool samples too.  Stool cultures are not routinely indicated in immunocompetent children with non-bloody diarrhoea.

Confirmation of viral gastroenteritis after the child has been discharged from the ED, and likely on the road to recovery at home, adds very little to (A) the clinical diagnosis of viral gastroenteritis in the ED, (B) the management plan and (C) the clinical outcome. 

Should the investigation influence management, then stool sampling may be of benefit.  This could be applicable where an outbreak may be suspected in school or creche, where there may be a public health benefit.

Stool samples should be sent in cases of bloody diarrhoea, immunodeficiency and recent foreign travel.

How about tests for dehydration? Sadly there is no one test that correlates clinically with dehydration. Urine specific gravity in infants is unreliable because the kidney reaches adult concentrating abilities after the age of 1.  Also, the child often doesn’t begin urinating until rehydration has begun.

And glucose? Well, almost 10% of GE patients aged 1 month to 5 years in high income countries present with hypoglycaemia.  Risk factors for hypoglycaemia on presentation include a longer duration of vomiting and increased frequency of vomiting.  It would be reasonable to consider point of care glucose testing at triage for young children as identifying hypoglycaemia on clinical ground alone is difficult in this age group. 

Prevention

The key to reducing the burden (and generally for an all-round happier life!) is in the prevention of acute gastroenteritis.  Rotavirus vaccination is now commonplace thought the antibodies, the UK & Ireland and other countries around the world.  It is very effective.

In the home and in the ED…Handwashing, handwashing, handwashing!

Vaccination leads to a profound reduction in presentations and admissions and a fall in overall seasonal workload, often within the first year after the introduction of universal vaccination against rotavirus.  Even though only those under 1 year old are generally vaccinated, it has been shown to contribute to a significant herd effect with fewer cases than expected in older children. In Scotland, where initial vaccine uptake was 93- 94% during the first 2 years, annual rotavirus confirmed gastroenteritis cases fell by 84.7%, bed days reduced by 91% (from 325 to just 29), without any documented cases of intussusception.  Reductions were seen across all age groups despite only infants receiving the vaccine.  Similar results can be seen in other areas of the UK and Ireland.

The not to miss bits

  • Do not assume isolated vomiting in a child is gastroenteritis.  Consider other causes -these very widely from inborn errors of metabolism to diabetes mellitus, surgical obstruction to urinary tract infections. If you’d like to hear more, check out Dani’s talk on vomiting in children in DFTB Essentials.
  • Beware chronic diarrhoea in an infant – do they have malabsorption or is this a presentation of IBD or an immunodeficiency?
  • Beware the non-thriving child with diarrhoea.
  • And beware chronic diarrhoea.

But what happened to Conor?

Conor was given a cup of Dioralyte ORS and his favourite beaker filled with Dioralyte.  His mum was encouraged to give him syringes of 5 mls of Dioralyte frequently or for him to take sips from his beaker and was asked to document on a piece of paper how many he received.  He vomited after 30 minutes of this therapy.

You give him a dose of Ondansetron and place an NG tube and give him 100mls (10ml/kg) over 1 hour after deciding he does not need rapid rehydration but slightly more than normal maintenance.  He then receives maintenance volumes of Dioralyte via his NG, which he tolerates well and then starts to take his own sips from his beaker.

He does not vomit in the ED again, has one episode of loose stools, passes urine, and is tolerating fluids orally.  He’s smiling at you! You feel he can be discharged and council his mum regarding regular fluid intake, choice of fluids, of any red flags, and encouraged to return in the event of any concern.

Conor’s Dad calls to say that Conor’s 3 year old sister at home is now vomiting too!  But it’s OK – He’s not too worried about her and Conor’s Mum has advised his Dad to start giving her regular sips of Dioralyte at home…

References

Colletti JE, Brown KM, Sharieff GQ, Barata IA, Ishimine P. The Management of Children with Gastroenteritis and Dehydration in the Emergency Department. J Emerg Med [Internet]. 2010;38(5):686–98. Available from: https://dx.doi.org/10.1016/j.jemermed.2008.06.015

Elliott EJ. Acute gastroenteritis in children. Br Med J. 2007;334(7583):35–40.

Vecchio A Lo, Dias A, Berkley JA, Boey C, Cohen MB, Cruchet S, et al. Comparison of Recommendations in Clinical Practice Guidelines for Acute Gastroenteritis in Children. Gastroenterology. 2016;63(2):226–35.

Freedman SB, Willan AR, Boutis K, Schuh S. Effect of dilute apple juice and preferred fluids vs electrolyte maintenance solution on treatment failure among children with mild gastroenteritis: A randomized clinical trial. JAMA – J Am Med Assoc. 2016;315(18):1966–74.

BK F, A H, JC C. Enteral vs Intravenous regydration therapy for children with gastroenteritis: A meta-analysis of randomized controlled trials. Arch Paediatr Adolesc. 2004;158(1):483–90.

Hartling L, Bellemare S, Wiebe N, Kf R, Tp K, Wr C, et al. Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children (Review). 2006;

Fedorowicz Z, Jagannath V, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. [Internet]. Cochrane database of systematic reviews. 2011. Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005506.pub5/full

NICE. Management of vomiting omiting in children and y young oung people with gastroenteritis : ondansetron. NICE GUIDELINES. 2014. p. 1–20.

Szajewska H, Guarino A, Hojsak I, Indrio F, Kolacek S, Shamir R, et al. Use of Probiotics for Management of Acute Gastroenteritis : A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics. 2014;58(4):531–9.

Forrest R, Jones L, Willocks L, Hardie A, Templeton K. Impact of the introduction of rotavirus vaccination on paediatric hospital admissions , Lothian , Scotland : a retrospective observational study. 2017;323–7.

MARLOW RD, MUIR P, VIPOND I, TROTTER CL FA. Assessing the impacts from the first year of rotavirus vaccination in the UK. Arch Dis Child. 2015;100(Supl 3):A30.

The 44th Bubble Wrap

Cite this article as:
DFTB, T. The 44th Bubble Wrap, Don't Forget the Bubbles, 2020. Available at:
https://dontforgetthebubbles.com/the-44th-bubble-wrap/

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: Neurodevelopmental outcomes at the edge of viability.

Metabolic presentations part 2: children and adolescents

Cite this article as:
Taciane Alegra. Metabolic presentations part 2: children and adolescents, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28592

Neurological symptoms in a healthy teen

Jane, 14 years old, is brought in by ambulance, unconscious after a 20-minute generalized tonic-clonic seizure at home. She’s wheeled into resus, and while she has a cannula inserted, you take a history from her father. You learn that she has been a healthy child who’s never had a seizure before, with no chronic conditions, no history of drug abuse, no acute illness, and no sick contacts. She’s a vegetarian and enjoys dancing. She’s started a new ‘intermittent fasting diet’ and yesterday hadn’t eaten since brunch. She went to bed early and this morning her mother was woken early by strange sounds coming from Jane’s room and found her seizing on the floor. 

Her primary survey shows that she’s maintaining her airway, is tachypnoeic with oxygen saturations of 98% in air and clear lungs, a normal cardiovascular examination and a GCS of 10, with global hyperreflexia.

This adolescent has an acute onset of neurological symptoms. The differential diagnoses are broad, but her symptoms were precipitated by a new diet that required prolonged fasting. This case is a red flag for a metabolic condition! 

The RCPCH Decreased Consciousness (DeCon) guideline lays out an approach to the child with a decreased conscious level, including differentials, investigations and management (take a look at the DeCon poster and summary guidance). 

You send some bloods and, as suggested by the RCPCH DeCon guideline, you include an ammonia.

Some points to remember

Common things are common: sepsis, CNS infections, intoxication (prescribed and recreational drugs), and primary seizure disorders should all be considered here, but extend your differentials to conditions that can be individually rare but are common as a group: metabolic diseases.

All children presenting with a decreased conscious level, regardless of age, should have an ammonia sent as part of their initial investigation in ED… this could be a case of an undiagnosed urea cycle defect. 

In late onset urea cycle defects, acute metabolic encephalopathy develops following metabolic stress precipitated by a rapid increase in nitrogen load from: 

  • infection
  • trauma
  • rapid weight loss and auto-catabolism
  • increase in protein turnover from steroids
  • surgery and childbirth
  • or other precipitants of protein catabolism.

Adolescents and adults with an undiagnosed urea cycle defect may be completely fit and well, but may have chronic symptoms such as headache, cyclical vomiting, behavioural difficulties, psychiatric symptoms or mild learning difficulties.

They may be selective vegetarians, restricting their protein intake.

Between episodes patients are relatively well. However, acute presentations can be fatal or patients may be left with a neurological deficit.

For more information about cycle urea disorders, check out Metabolic presentations part 1.

The take home

Always send an ammonia in any child presenting with an acute encephalopathy or decreased GCS.

Disorders involving energy metabolism

Next up is Liz, a patient with a diagnosed metabolic disorder.

Liz is a 3-year-old girl from the countryside, who is visiting her grandmother in the city. She has had diarrhoea since yesterday and started vomiting last night. In the last 3 hours, she hasn’t been able to tolerate anything orally. There has been no fever or respiratory symptoms and she is passing urine as normal. Her 5-year-old cousin has similar symptoms. 

Her Grandmother informs you that Liz has MCAD deficiency and her emergency plan was tried at home, without success. Liz is not usually treated at your hospital and you don’t have her chart. Unfortunately, Liz’s grandmother didn’t bring the plan to the hospital. 

Liz looks tired and is mildly dehydrated, but smiles at you. Her heart sounds are normal and her chest is clear. She has increased bowel sounds, a soft abnormal with mild diffuse pain on deep palpation and no masses or organomegaly. She’s afebrile but tachycardic at 165, her capillary  refill time is 3 seconds, and her systolic BP is 104mmHg.

You put in a cannula and measure bedside glucose and ketones. Liz has a hypoketotic hypoglycaemia.

What is MCAD deficiency?

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder in Caucasians in Northern Europe and the United States. Most children are now diagnosed through newborn screening. In fatty acid oxidation disorders, the body can only partially break down fat.

Let’s recap some basic biochemistry: in prolonged fasting, the body’s normal response is to break down fat to create ketones, as an alternative source of energy. However, children with MCAD deficiency can’t produce large amounts of ketones, so their ketone response is not appropriate to the degree of hypoglycaemia. 

Clinical symptoms in a previously apparently healthy child with MCAD deficiency include hypoketotic hypoglycemia and vomiting that may progress to lethargy, seizures, and coma, triggered by a common illness. Hepatomegaly and liver disease are often present during an acute episode. These children appear well at birth and, if not identified through newborn screening, typically present between 3 and 24 months of age, although presentation even as late as adulthood is possible. The prognosis is excellent once the diagnosis is established and frequent feedings are instituted to avoid any prolonged periods of fasting (Merritt and Chang, 2019).

Children with fatty acid oxidation disorders (medium, long and short chain defects) have typical acylcarnitine patterns. This is one of the reasons acylcarnitines are sent as part of metabolic and hypoglycaemia work-ups.

What is the priority in acute presentations?

Children who have MCADD, like Liz, need extra calories when sick. The most important intervention is to give simple carbohydrates by mouth, such as glucose tablets or sweetened, non-diet beverages, or intravenously if needed to reverse catabolism and sustain anabolism. In Liz’s case, she’s vomiting all oral intake so cannot tolerate oral carbohydrates, so the intravenous route is necessary. 

The key priorities are:

  • Correct hypoglycaemia immediately with 200mg/kg glucose: 2 ml/kg of 10% glucose or 1ml/kg of 20% glucose, over a few minutes. 
  • Treat shock or circulatory compromise with a bolus of 20ml/kg 0.9% sodium chloride. 
  • Give maintenance fluids with potassium once the plasma potassium concentration is known and the child is passing urine. 

Where can you find resources?

The British Inherited Metabolic Disease Group, BIMDG, has specific guidance on their website.

Disorders involving storage of complex molecules

Mike is 12 years old, presenting to the ED with cough and fever. He has been coughing for 10 days, worse progressively in the last 5  and febrile for the last 3 days. He’s been lethargic since yesterday and even when afebrile he looks unwell. His appetite is poor and he has been “sipping some apple juice”. You learn from his mother that he has a condition called Mucopolysaccharidosis (MPS) type I and is receiving treatment with “the enzyme”. Every now and again, “he is chesty and needs to come to hospital”. 

You examine Mike. He’s pink and well hydrated, but looks sick. You notice that he is shorter than an average 12 year old boy, has hand contractures and coarse facial features. 

He has a soft systolic cardiac murmur with good pulse volume. On auscultating his chest you hear creps and rhonchi on the right side. He has mild hepatomegaly and an umbilical hernia. 

His temperature is 37.5ºC, heart rate is132, respiratory rate 30, and oxygen saturations are just 88% in air.

A bit about mucopolysaccharidoses (MPS)

In mucopolysaccharidosis disorders, the body is unable to break down mucopolysaccharide sugar chains. These mucopolysaccharide sugars build up in cells, blood and connective tissue: hence the name, ‘storage disorders’.

In general, most affected people appear healthy at birth and experience a period of normal development, followed by a decline in physical and/or mental function.

As the condition progresses, it may affect appearance; physical abilities; organ function; and, in most cases, cognitive development. 

Most cases are inherited in an autosomal recessive manner, although one specific form (Type II) follows an X-linked pattern of inheritance. 

Specific treatment can be provided via enzyme replacement therapy or haematopoietic stem cell transplantation in the early stages. 

Presently, enzyme replacement therapy is available for MPS I, II and VI and is given as an intravenous infusion either weekly or biweekly, depending on the disease. 

Both enzyme-replacement and haemotopoietic stem cell treatments still have gaps and few clinical trials supporting them. (rarediseases.info; Dornelles et.al, 2014).

What treatment should be started in the ED?

Patients with Mucopolysaccharidosis don’t require any emergency treatment in the ED for their underlying metabolic disease. They are, however, at increased risk of respiratory infections.

Mike is likely to have a community acquired pneumonia and needs to be treated accordingly with oxygen and antibiotics.

References

Adam , HH. Ardinger, RA. Pagon, S. E. Wallis, L. J. H. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews® [online book]

Merritt JL,  Chang IJ. Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency.  GeneReviews® [online book], June 2019. Available at  https://www.ncbi.nlm.nih.gov/books/NBK1424/

Genetic and Rare Diseases Information Center (GARD) https://rarediseases.info.nih.gov/diseases/7065/mucopolysaccharidosis 

Dornelles AD et al. Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network. Genet Mol Biol. 2014

Volcano

Managing Gastro-Oesophageal Reflux Disease

Cite this article as:
Sarah Davies. Managing Gastro-Oesophageal Reflux Disease, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.29563

Isobel is a 10 week old, exclusively breast-fed, baby girl. She is brought into the Emergency Department with a history of frequent vomiting and poor weight gain. Her examination is normal, but when you ask Isobel’s exhausted-looking mother to put her to the breast, she becomes fractious and fussy, pulling away, arching her back, and taking very little feed at all.  

What are you going to do? 

At face value, this familiar presentation sounds like gastro-oesophageal reflux disease (GORD), although the differential for a ten-week old with vomiting and weight loss is wide.

Gastro-oesophageal reflux (GOR) is …the effortless retrograde passage of gastric contents into the oesophagus, with or without overt regurgitation. 

It is:

  • Physiological, due to low tone in the immature lower oesophageal sphincter
  • Common, occurring in up to 50% infants under 6m
  • Frequent – can happen up to x6/day

Gastro-oesophageal reflux disease (GORD) can be diagnosed clinically when GOR is accompanied by troublesome symptoms that affect everyday functioning (eg crying, back-arching, food refusal) and may lead to complications (eg failure to thrive).

Alternative diagnoses should be considered when there are additional red flag features (see below) indicative of a different pathology and under these circumstances, investigations should be tailored to rule these in or out.

*Some red flags overlap with symptoms directly related to GORD. The number, duration and severity of these should inform your decision to investigate on a case by case basis

As Isobel has symptoms of GORD with faltering growth you check her head circumference (which is appropriate), dip a urine (which is negative), and send some bloods for a faltering growth screen (although you strongly suspect they will come back as normal). You explain to Isobel’s mother that there is a stepwise approach to the management of GORD starting with non-pharmacological measures.

So, in the absence of red flag symptoms, do I need to prove its GORD?

In short, no. There is no single gold standard test for the diagnosis of GORD, hence the emphasis on clinical diagnosis. 

Invasive testing does have a place, though it is rarely the job of an ED clinician to be considering this. 

Endoscopy is used under the guidance of a Paediatric Gastroenterologist, for infants who fail to respond to optimal medical management. This will diagnose erosions and eosinophilic oesophagitis. 

pH MII (multi-channel intraluminal impedance) monitoring is used in children whose symptoms persist despite optimal medical therapy with normal endoscopy.   For a great explanation of this technique this previous DFTB post on reflux from 2016

Barium is out. Reliable biomarkers don’t yet exist. Scintigraphy, ultrasound and trial of a proton-pump inhibitor (PPI) are not useful in babies. 

OK, so I only need to investigate if I think there may be another cause for the symptom. But what should be my initial approach to treatment?

  • Positional management?
  • Avoiding overfeeding?
  • Thickening feeds?

Positional management – keeping the baby upright after feeds and elevating the head of the cot to sleep – is often advised for reflux. However, a study by Loots and colleagues in 2014 showed that regurgitation was only reduced through the use of side-lying positions which should NEVER be recommended due to the increased risk of SIDS. Head elevation made no difference at all despite some evidence that it can be beneficial in adults. 

And whilst a common-sense approach would support a move to smaller more frequent feedings and keeping a baby upright for 20-30 minutes after a feed, there isn’t any good quality evidence that confirms this. 

Feed thickeners have been shown repeatedly to reduce the frequency of visible regurgitation episodes in babies with reflux and in some studies to decrease cry/fuss behaviour too. They are safe and come highly recommended as a first-line intervention for babies with troublesome reflux. If you are going to advise a thickener for a breastfed infant, it’s important to suggest a carob bean-based product, such as Carobel, because the amylase in breast milk will digest the rice cereal-based thickeners such as Cerelac.  

Acupuncture, probiotics, massage, hypnotherapy have not yet been adequately studied for us to say one way or another if they are of any benefit. And alginates, probably the most familiar to us being Gaviscon? We’ll cover those shortly.

The key thing to remember for any intervention, is to reserve these for your patients with GORD. Happy, thriving, refluxy babies, typically outgrow their symptoms as they transition to solid food and should be left well alone

OK, but what if my patient has tried these already? What should I advise next? 

First, check how long they have persisted with the intervention. 

One of the biggest reasons for the simpler interventions not to help with GORD is that they are not given enough time to make a difference. Having said that, if a tired parent is repeatedly confronted with a grizzly, uncomfortable baby who is refusing to feed, asking them to persevere for two weeks with an intervention they don’t think is helping, may be practically difficult to achieve. 

In the UK, we have a choice of two key guidelines to help us with the next steps in reflux management.  

  1. NICE, last updated 2019

OR

  1. ESPGHAN/NASPGHAN 2018 joint consensus guidelines which are endorsed and recommended by our own BSPGHAN
  • European Society of Paediatric Gastroenterology, Hepatology and Nutrition
  • North American Society of Paediatric Gastroenterology, Hepatology and Nutrition
  • British Society of Paediatric Gastroenterology, Hepatology and Nutrition

Except that these guidelines differ a little on the advice they give for when simple measures don’t help…

NICE recommend a trial of Gaviscon first, and if that doesn’t work 4-8 weeks of a PPI such as omeprazole, and only then suggest a trial of cow’s milk protein exclusion (either through use of a hydrolysed formula or maternal dairy exclusion in breastfed infants) as a last resort, if reflux does not improve after ‘optimal medical management’. 

NASPGHAN/ESPGHAN on the other hand, suggest that ALL infants undergo an initial trial of cow’s milk protein exclusion, and only if this fails do they suggest the use of a PPI or hydrogen receptor antagonist (H2RA) such as Ranitidine. The bottom line is, that no-one has looked at the efficacy of a cow’s milk protein-free diet for symptom relief in babies presenting with reflux as the single symptom of cow’s milk protein intolerance (CMPI).  

The NASPGHAN team argues, that whilst there is no evidence on the topic, there are a number of babies with CMPI manifesting as reflux only who will benefit from this approach. They suggest eliminating cow’s milk protein from an infant’s diet for a minimum of 2 weeks, ideally four. If symptoms resolve and reappear on reintroduction then the diagnosis is clear. 

NASPGHAN then suggest babies who do not respond should be referred to secondary care services and started on a time-limited trial of PPI. 

This is largely so that infants are not left struggling on inadequate therapy for long periods of time, but also because their review found conflicting evidence around the benefit and side effect profile of these medications for young children. 

In six studies looking at PPI versus placebo, four studies showed no difference in regurgitation or other reflux associated symptoms between intervention and control groups. Three studies comparing H2RAs to placebo did show some benefit of the intervention, however, these studies were all in older children with biopsy-proven erosive oesophagitis up to 8 years of age.  Two studies showed endoscopic and histological and clinical features of GORD were reduced with H2RA over placebo, but these were in mixed-age groups including children up to 8 years old.

All studies showed a similar profile of side effects and between drug and placebo arms, however, one study demonstrated an increased rate of infection, in particular lower respiratory tract infection and diarrhoea in the PPI group. 

Given these findings, NASPGHAN cautiously recommends PPI or H2RA therapy in babies who have troublesome reflux despite trying a number of other non-pharmacological management options. 

Their key message is around early referral to secondary care, giving sufficient time for any one intervention to work, and making sure children are appropriately followed up.

So, what should I do? 

Given the somewhat conflicting advice outlined by these two well-respected groups, you could be left feeling unsure how to manage your next case. However, the genuine gap in the evidence market here does mean you are free to exercise your own clinical judgment and tailor your decision making to each individual refluxy baby, whilst empathetically taking on board the thoughts and preferences of the family.  This could, for some babies and parents, be medicine in itself. 

And what about alginates?

Two studies in the large literature review by the NASPGHAN/ESPAGHN group, compare Gavsicon to placebo. They show a reduction in visible regurgitation but no difference in reflux-associated symptoms. Furthermore, infants treated with alginate and then undergoing pH MII for 24 hours, showed no difference in the frequency of regurgitation events between groups. 

Chronic use of alginates causes constipation and poses a theoretical risk of milk-alkali syndrome, which is perhaps why the authors suggest use is limited to short term therapy. NICE do recommend a trial of Gaviscon therapy at an early stage in their pathway, as an alternative to feed thickener, but again on a time-limited basis with a planned review. 

Isobel’s mother had already tried two weeks of feed thickener on recommendation from the GP with no improvement. She was keen to avoid medication if possible so you agreed to a trial of dietary cow’s milk elimination for Mum who would continue to breastfeed and give top-ups with a hydrolysed formula if there was still no weight gain in a week. You gave her a sheet of dietary advice to ensure she maintained her own calcium intake and asked her to see the GP in 2 weeks for a review.  

Take home message

  • The vomiting infant has a wide differential – actively look for red flag features and investigate if you are concerned.
  • Infants with GORD need a management plan; infants with GOR, leave well alone
  • Start simply with an intervention that the family are happy to trial
  • Give time for it to work (up to two weeks)
  • Ensure follow-up for all and onward referral for infants who require acid-suppressive medication 

References

  1. Loots et al. Body positioning and medical therapy for infantile gastroesophageal reflux symptoms. Journal of Pediatric Gastroenterology and Nutrition 2014; 59 (2): 237-243. 
  2. Rosen et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. JPGN 2018; 66(3): 516-554. 
  3. Winter et al. Efficacy and safety of pantoprazole delayed release granules for oral suspension in a placebo-controlled treatment withdrawal study in infants 1-11 months old with symptomatic GERD. JPGN 2010; 50: 609-618.  
  4. Orenstein et al. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. Journal of Pediatrics 2009; 154: 514-520e4. 
  5. Davidson et al. Efficacy and safety of once daily omeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. Journal of Pediatrics 2013; 163: 692-698.e1-2. 
  6. Winter et al. Esomeprazole for the treatment of GERD in infants ages 1-11 months. JPGN 2012; 55: 14-20. 
  7. Hussain et al. Safety and efficacy of delayed release rabeprazole in 1-11 month old infants with symptomatic GERD. JPGN 2014; 58: 226-236. 
  8. Moore et al. Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux. Journal of Pediatrics 2003; 143: 219-223. 
  9. Cucchiara et al. Cimetidine treatment of reflux oesophagitis in children: an Italian multi-centric study. JPGN 1989; 8: 150-156. 
  10. Orenstein et al. Ranitidine, 75mg, over the counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux. Alimentary Pharmacology and Therapeutics 2002; 16: 899-907. 
  11. Simeone et al. Treatment of childhood peptic esophagitis: a double-blind placebo-controlled trial of nizatidine. JPGN 1997; 25: 51-55. 
  12. Miller et al. Comparison of the efficacy and safety of a new aluminium free paediatric alginate preparation and placebo in infants with recurrent gastroesophageal reflux. Current Medicines and Research Opinion 1999; 15: 160-168. 
  13.  Ummarino et al. Effect of magnesium alginate plus simethicone on gastro-oesophageal reflux in infants. JPGN 2015; 60: 230-235.

The 43rd Bubble Wrap

Cite this article as:
DFTB, T. The 43rd Bubble Wrap, Don't Forget the Bubbles, 2020. Available at:
https://dontforgetthebubbles.com/the-43rd-bubble-wrap/

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: Is Ketamine the go-to for ET Intubation in critically ill kids?

Picture of house

Hospital in the Home

Cite this article as:
Jo Lawrence. Hospital in the Home, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28959

Elise is about to have her 8th birthday and has planned a small party at home with her family and two best friends.  Elise also has acute lymphoblastic leukaemia and is in the middle of chemotherapy treatment.  Her next dose of methotrexate is due the day after her birthday but requires pre-hydration the day before….

Thomas is in year 3 and loves playing foursquare at lunch with his friends. He also has CF and requires regular tune-ups of 2 weeks IV antibiotics and physiotherapy…..

MaryKate is an 8 month old and the youngest of 5 children.  She has poor oral feeding due to a complex medical background and requires nasogastric top-ups. Her parents have been told that she could wean from the tube if she participated in an intensive multidisciplinary program but are reluctant to attend hospital due to the significant disruption on family routine…..  

Is there a way Elise could enjoy her birthday at home, Thomas stay active at school and MaryKate receive the treatment she needs without significant family disruption?

What is Hospital in the Home?

Hospital in the Home (HITH) refers to hospital level care provided in the home environment. 

As we look at managing our growing population with a fixed number of hospital beds this is one area of healthcare that is set to boom!  

When admitted to HITH, clinicians visit the home and provide the acute care interventions required in 1-2 visits per day.  The advantages of this model of care on hospital flow and access are readily apparent.  Less obvious, although equally critical, are the substantial benefits for the family and patient.  Being treated in a safe place surrounded by familiar faces eases the stress and anxiety experienced by the child. Cost-savings for families obviously include not having to fork out for travel and hospital parking, but the real cost-savings occur for families because both parents no longer have to take carers leave – one for the hospitalized child, the other for the siblings. On average, HITH ends up being one-third of the cost of hospitalization for families1. In addition, HITH avoids disruption to family routines and unwanted separation.

So what can Hospital in the Home do?

Pretty much anything!  As long as the patient is clinically stable (not heading for ICU) and can have their care needs delivered in up to 2 visits per day, then it can be done.  

Traditionally Hospital in the Home models have centred around IV antibiotics and little else, but that has dramatically changed over the past few years. 

Here are some of the common things that paediatric HITHs are currently doing2:

  • Diabetes education
  • Eczema dressings
  • Subcutaneous infusions
  • Chemotherapy
  • Pre and post-hydration for chemotherapy
  • TPN hook ons and hook offs
  • Wound dressings
  • NG feed support
  • Cardiac monitoring
  • CF tunes ups
  • Physiotherapy 
  • IV antibiotics 

Baseline criteria regarding distance from hospital and safety of home environment exist but solutions exist for almost situations.

Although most centres service a certain distance from hospital, care can often be outsourced for children who live more rurally.  The care continues to be managed by the tertiary hospital but provided by local care teams – a superb option.

In cases where a barrier exists for staff to enter the home, creative solutions can be found by meeting children at school, in parks or family member’s homes.  

What has changed with Covid-19?

Whilst paediatric hospitals in general saw a fall in patient presentations, HITH referrals have sky-rocketed.  Doctors and families have experienced renewed interest in moving vulnerable patients out of hospital walls and away from the potential of cross-infection.  Stricter visitor restrictions meant hospitalisation had an even greater impact on family life and the driver to manage care at home wherever possible has grown.

Most of this growth has been through increasing the proportion of eligible children referred rather than creating new pathways.  A couple of children have been admitted for observation of Covid-19 infection, but these cases have been few and far between.

However, as with every area of healthcare delivery, the biggest changes for HITH have been moving with the technology.  Education visits, medical and nursing reviews and physiotherapy have all been converted to telehealth where safe to do so.

Vaccination for influenza was offered to all patients admitted to HITH and was accepted by 70% of eligible patients.  65% of these were being vaccinated for the first time against flu3.  In an environment where routine vaccinations have been falling4, this is a powerful demonstration of the opportunities that exist within HITH.

Infants with bronchiolitis have been managed through HITH before5 but the care pathway has never stuck due to barriers accessing cylinders on the same day and clinician confidence.  A new model has been rolled out overcoming these barriers through utilising oxygen concentrators and remote monitoring.

With time, our use of remote monitoring and ability to feed vital signs directly into the Electronic Medical Record, will allow massive expansion of HITH services.   Predictive modelling from large EMR datasets will allow more accurate prediction of which children are likely to be safely transferred to the home environment.  Realtime data and predictive modelling will enhance clinician and family confidence and enable us to fully realise the benefits of HITH to hospitals and families.  

So what about our friends Elise, Thomas and MaryKate….

Elise is able to receive her pre-hydration at home on her birthday.  She celebrates her birthday in her parent’s bed with her sister beside her, both building her new lego sets.  Her best friends visit and her mother prepares a special meal and bakes a special cake.  She is able to go to bed that night, knowing the HITH nurses will visit every day over the following week to administer her chemotherapy and post-hydration and she has avoided another week in hospital.

The HITH nurses visit Thomas daily before school to connect his longline to a Baxter antibiotic infusion. Before and after school he performs physiotherapy via telehealth.  At school, he wears his antibiotic in a backpack and can continue to play 4 square at lunch.

MaryKate is visited by the HITH dietitian and speech therapy who provide feeding advice and a regime that fits around the family routine. They can see where MaryKate sits for meals and how her meals are prepared first hand and are able to offer some helpful suggestions. The team are also able to visit MaryKate at her daycare and ensure her routine is consistent. In between visits, MaryKate is reviewed via telehealth by the allied health team.  She makes significant oral progress and by the end of 2 weeks, her tube is no longer required.

Bubble Wrap Plus – September 2020

Cite this article as:
Anke Raaijmakers. Bubble Wrap Plus – September 2020, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.29169

Here is a new Bubble Wrap Plus, our monthly paediatric Journal Club List provided by Professor Jaan Toelen & his team of the University Hospitals in Leuven (Belgium). This comprehensive list of ‘articles to read’ 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 month’s list features answers to intriguing questions such as: ‘What is the effect of longer resuscitations at birth on neurodevelopment?’, ‘Is it necessary to evaluate urinary tract infection in children with lower respiratory tract infection?’, ‘What is the effect of social distancing on ‘regular’ URTIs?’, ‘Does maternal pertussis vaccination interfere with neonatal vaccination?’ and ‘Is migraine a common cause for nystagmus in the emergency department?’.

1.Reviews and opinion articles

Thinking fast and slow in the evaluation of injury plausibility in child protection.

Skellern C J Paediatr Child Health. 2020 Aug 11.

The Suffering Child: Claims of Suffering in Seminal Cases and What To Do About Them.

Friedrich AB. Pediatrics. 2020 Aug;146(Suppl 1):S66-S69.

Childhood Sexual Abuse: A Call to Action in Pediatric Primary Care.

Ghastine L, et al . Pediatrics. 2020 Aug 4:e20193327.

Kawasaki disease fact check: Myths, misconceptions and mysteries.

Butters C, et al. J Paediatr Child Health. 2020 Aug 8.

Follow the complex bread crumbs: A review of autoinflammation for the general paediatrician.

Tsoukas P, et al. Paediatr Child Health. 2020 Aug;25(5):279-285.

Plant-Based Milks: A Possible Therapeutic Tool if Correctly Labeled and Prescribed.

Mennini M, et al . J Pediatr Gastroenterol Nutr. 2020 Jul 30.

The Liver in Sickle Cell Disease.

Lacaille F, et al . J Pediatr Gastroenterol Nutr. 2020 Jul 30.

Management of Post-hemorrhagic Ventricular Dilatation in the Preterm Infant.

El-Dib M, et al . J Pediatr. 2020 Jul 30:S0022-3476(20)30978-1.

Update on the COVID-19-associated inflammatory syndrome in children and adolescents; paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2.

Singh-Grewal D, et al . J Paediatr Child Health. 2020 Jul 31.

2. Original clinical studies

Early Feeding in Acute Pancreatitis in Children: A Randomized Controlled Trial.

Ledder O, et al. Pediatrics. 2020 Aug 12:e20201149.

The Safety of Early Enteral Feeding in Children With Acute Pancreatitis.

Hamilton-Shield J, et al. Pediatrics. 2020 Aug 12:e2020007211.

Duration of Resuscitation at Birth, Mortality, and Neurodevelopment: A Systematic Review.

Foglia EE, et al. Pediatrics. 2020 Aug 12:e20201449.

Is it necessary to evaluate urinary tract infection in children with lower respiratory tract infection?

Kim JM, et al. J Paediatr Child Health. 2020 Aug 8.

Use of oximetry to screen for paediatric obstructive sleep apnoea: is one night enough and is 6 hours too much?

Galway NC, et al. Arch Dis Child. 2020 Aug 11:archdischild-2019-318559.

Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Responses.

Yonker LM, et al . J Pediatr. 2020 Aug 18:S0022-3476(20)31023-4.

Effect of Social Distancing Due to the COVID-19 Pandemic on the Incidence of Viral Respiratory Tract Infections in Children in Finland During Early 2020.

Kuitunen I, et al. Pediatr Infect Dis J. 2020 Jul 28.

Masked paediatricians during the COVID-19 pandemic and communication with children.

Shack AR, et al. J Paediatr Child Health. 2020 Aug 8.

Role of children in household transmission of COVID-19.

Kim J, et al. Arch Dis Child. 2020 Aug 7:archdischild-2020-319910.

Prevalence of SARS-CoV-2 Infection in Children Without Symptoms of Coronavirus Disease 2019.

Sola AM, et al . JAMA Pediatr. 2020 Aug 25.

Increased incidence of complicated appendicitis during the COVID-19 pandemic.

Lee-Archer P, et al . J Paediatr Child Health. 2020 Aug;56(8):1313-1314.

Is Nasopharyngeal Swab Comparable With Nasopharyngeal Aspirate to Detect SARS-CoV-2 in Children?

Capecchi E, et al . Pediatr Infect Dis J. 2020 Jul 21.

Community-Based Epidemiology of Hospitalized Acute Kidney Injury.

Parikh RV, et al. Pediatrics. 2020 Aug 11:e20192821.

Endocarditis prophylaxis in daily practice of pediatricians and dentists in Flanders.

De Wolf D, et al. Eur J Pediatr. 2020 Aug 11.

A 10-year retrospective survey of acute childhood osteomyelitis in Stockholm, Sweden.

von Heideken J, et al. J Paediatr Child Health. 2020 Aug 11.

Virtual reality for intravenous placement in the emergency department-a RCT

Goldman RD, et al. Eur J Pediatr. 2020 Aug 10.

Bedside Airway Ultrasound in the Evaluation of Neonatal Stridor.

Oulego-Erroz I, et al. J Pediatr. 2020 Aug 6:S0022-3476(20)30993-8.

Normal fecal calprotectin levels in healthy children are higher than in adults and decrease with age.

Velasco Rodríguez-Belvís M, et al. Paediatr Child Health. 2020 Aug;25(5):286-292.

Can Use of Cerebral Oxygenation Predict Developmental Outcomes in Preterm Infants With NEC?

Horne RSC.Pediatrics. 2020 Aug 26:e2020014407.

Cerebral Oxygenation in Preterm Infants With Necrotizing Enterocolitis.

Howarth C, et al .Pediatrics. 2020 Aug 26:e20200337.

Junior doctor perceptions of education and feedback on ward rounds.

Modak MB, et al . J Paediatr Child Health. 2020 Aug 26.

Treatment of Postural Orthostatic Tachycardia Syndrome With Medication: A Systematic Review.

Hasan B, et al . J Child Neurol. 2020 Aug 24:883073820948679.

Synchronized Inflations Generate Greater Gravity Dependent Lung Ventilation in Neonates.

Dowse G, et al . J Pediatr. 2020 Aug 19:S0022-3476(20)31029-5.

Maternal Stress During Pregnancy Predicts Infant Infectious and Non-infectious Illness.

Bush NR, et al . J Pediatr. 2020 Aug 19:S0022-3476(20)31027-1.

A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes.

Breton MD, et al . N Engl J Med. 2020 Aug 27;383(9):836-845.

Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial.

Forno E, et al . JAMA. 2020 Aug 25;324(8):752-760.

Interference With Pertussis Vaccination in Infants After Maternal Pertussis Vaccination.

Abu-Raya B, et al . Pediatrics. 2020 Aug 4:e20193579.

Management of pain in newborn circumcision: a systematic review.

Rossi S, et al . Eur J Pediatr. 2020 Aug 3.

Extreme prematurity, growth and neurodevelopment at 8 years: a cohort study.

Hickey L, et al . Arch Dis Child. 2020 Aug 3:archdischild-2019-318139.

Genetic Susceptibility to Life-threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants.

López EL, et al . Pediatr Infect Dis J. 2020 Jul 17.

Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Extremely Low Gestational Age Infants.

Shankaran S, et al . J Pediatr. 2020 Jul 30:S0022-3476(20)30979-3.

Skin-to-skin care alters regional ventilation in stable neonates.

Schinckel NF, et al . Arch Dis Child Fetal Neonatal Ed. 2020 Jul 30:fetalneonatal-2020-319136.

School-age outcomes following intraventricular haemorrhage in infants born extremely preterm.

Hollebrandse NL, et al . Arch Dis Child Fetal Neonatal Ed. 2020 Jul 30:fetalneonatal-2020-318989.

Characteristics of Acute Nystagmus in the Pediatric Emergency Department.

Garone G, et al . Pediatrics. 2020 Aug;146(2):e20200484.

3. Guidelines and Best Evidence

Automated oxygen control in preterm infants, how does it work and what to expect: a narrative review.

Salverda HH, et al . Arch Dis Child Fetal Neonatal Ed. 2020 Jul 30:fetalneonatal-2020-318918.

Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder.

Loe IM, et al. JAMA Pediatr. 2020 Aug 10.

Clinical Management of Staphylococcus aureus Bacteremia in Neonates, Children, and Adolescents.

McMullan BJ, et al. Pediatrics. 2020 Aug 5:e20200134.

Universal screening of high-risk neonates, parents, and staff at a neonatal intensive care unit during the SARS-CoV-2 pandemic.

Cavicchiolo ME, et al. Eur J Pediatr. 2020 Aug 7:1-7.

Fluid management during diabetic ketoacidosis in children: guidelines, consensus, recommendations and clinical judgement.

Tasker RC. Arch Dis Child. 2020 Aug 26:archdischild-2020-320164.

Clinical Prediction Rule for Distinguishing Bacterial From Aseptic Meningitis.

Mintegi S, et al . Pediatrics. 2020 Aug 25:e20201126.

Reducing Antibiotic Prescribing in Primary Care for Respiratory Illness.

Kronman MP, et al . Pediatrics. 2020 Aug 3:e20200038.

Reopening schools during the COVID-19 pandemic: governments must balance the uncertainty and risks of reopening schools against the clear harms associated with prolonged closure.

Viner RM, et al . Arch Dis Child. 2020 Aug 3:archdischild-2020-319963.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper: Plant-based Milks.

Merritt RJ, et al . J Pediatr Gastroenterol Nutr. 2020 Aug;71(2):276-281.

Airborne Transmission of SARS-CoV-2: Theoretical Considerations and Available Evidence.

Klompas M, et al . JAMA. 2020 Aug 4;324(5):441-442.

4. Case Reports

A 16-Year-Old Boy With Cough and Fever in the Era of COVID-19.

Anderson KR, et al. Pediatrics. 2020 Aug 12:e2020008235.

An Infant Presenting with Large, Asymmetric Tongue.

Golomb MR, et al. J Pediatr. 2020 Aug 7:S0022-3476(20)30992-6.

Tracheal Buckling in a Young Child.

Miyamoto M, et al. J Pediatr. 2020 Aug 6:S0022-3476(20)30991-4.

Methaemoglobinaemia in two exclusively breastfed infants with food protein-induced enterocolitis syndrome.

Geljic A, et al. J Paediatr Child Health. 2020 Aug 7.

Recurrent pneumothorax in a child.

Rajvanshi N, et al . J Paediatr Child Health. 2020 Aug 5.

Sequential Retinal Hemorrhages in an Asymptomatic Child.

Ho DK, et al . J Pediatr. 2020 Jul 30:S0022-3476(20)30980-X.

Agranulocytosis and lymphopenia in neonate: A neonatal emergency.

Rustogi D, et al. J Paediatr Child Health. 2020 Aug 7.

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

Metabolic presentations part 1: neonates

Cite this article as:
Taciane Alegra. Metabolic presentations part 1: neonates, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28423

You are working in the Paediatric Emergency Department and are called in to see a neonate with a history of irritability and seizures. You enter the room and are told the following: “Emma is a 3 day old, term baby who has been refusing feeds and crying excessively. Her mother says she has been irritable since birth. There has been no history of fever or cough. At home she had seizure-like activity with tonic posturing”. When you examine her, you find an awake, extremely irritable baby with flexed upper limbs flexed, extended lower limbs and global hyperreflexia. She is not dysmorphic and has no cardiac murmurs, respiratory distress or abdominal organomegaly.

Babies cry (a lot!) and we all know that, however Emma is presenting some red flags: she’s irritable and has an acute onset of seizures, without any obvious trigger.

The basics

In this post we will discuss some acute metabolic presentations in the neonatal period, how to identify potential problems and emergency treatment in the ED. You don’t need to make a diagnosis (bonus points if you do) but do need to remember that spotting the zebra will lead to more favourable outcomes. Metabolic diseases / disorders are also called inborn errors of metabolism (IEM).

How common are metabolic conditions?

Individually, metabolic conditions are rare, most having an incidence of less than 1 per 100,000 births. However, when considered collectively, the incidence may reach 1 in 800 to 1 in 2500 births (Applegarth et. al, 2000; Sanderson et.al, 2006). 

Remember: some symptoms can be unspecific and can mimic sepsis; or a child with an undiagnosed metabolic condition can decompensate with an intercurrent infection. 

An easy-to-understand classification by Saudubray divides the IEM in three groups of disorders, depending on how they present. 

Intoxication disorders

An acute or progressive intoxication from the accumulation of toxic compounds, usually small molecules. 

These usually present with a symptom-free interval and clinical signs of ‘intoxication’, which may be acute, although can be intermittent.

  • disorders of amino acid catabolism: e.g. phenylketonuria, maple syrup urine disease, homocystinuria, tyrosinemia 
  • most organic acidurias: e.g. methylmalonic, propionic, isovaleric acidaemia
  • urea cycle defects: e.g. Ornithine transcarbamylase deficiency (OTC deficiency), Citrullinemia type I (ASS1 deficiency).
  • sugar intolerances: galactosemia
  • metals: Wilson’s, Menkes, hemochromatosis
  • porphyrias

Disorders involving energy metabolism

A deficiency in energy production or utilization, within the liver, myocardium, muscle, brain or other tissues. 

Common symptoms include hypoglycemia, hyperlactatemia, hepatomegaly, failure to thrive and cardiac failure. 

  • Mitochondrial defects: congenital lactic acidemias (defects of pyruvate transporter, pyruvate carboxylase, pyruvate dehydrogenase, and the Krebs cycle), mitochondrial respiratory chain disorders and the fatty acid oxidation defects (MCAD deficiency).
  • Cytoplasmic energy defects: disorders of glycogen metabolism (collectively known as glycogen storage diseases), hyperinsulinism.  

Complex molecules disorders

Problems in the synthesis or catabolism of complex molecules, leading to storage of big molecules. 

Symptoms are chronic, progressive and independent of intercurrent events or food intake. 

  • Mucopolysaccharidosis (I-IV, VI and VII). The eponymous names are used less frequently now, particularly in the literature, but you might come across them in clinical practice (MPS I, Hurler’s Syndrome; MPS II, Hunter’s Syndrome; MPS VI, Maroteaux- Lamy) 
  • Gaucher disease
  • Peroxisomal disorders: e.g. X-linked adrenoleukodystrophy (X-ALD) and Zellweger’s Syndrome.

Treatment strategies

Remember your biochemistry: a substrate is transformed by an enzyme into a product .

If there is a problem with the enzyme, the substrate will accumulate. If this substrate accumulation is a problem, we eliminate it, like avoiding protein in the diet or removing toxins with treatments such as ammonia scavengers.  If a lack of the product is the problem, we can supplement it (for example the administration of carbohydrate in glycogen storage disease). And for some diseases the  enzyme can be “corrected” with organ transplantation or enzyme replacement therapy.

A bonus on smells

Due to accumulation of “unusual” products in their body fluids, people with certain metabolic conditions have distinctive odours (better observed in urine, for practical reasons):

  • Maple syrup, burnt sugar, curry: Maple syrup urine disease
  • Sweaty feet: glutaric aciduria type II, isovaleric acidaemia
  • Cabbage: tyrosinemia
  • Mousy, musty: phenylketonuria
  • Rotting fish: trimethylaminuria
  • Swimming pool: Hawkinsinuria 

Back to Emma. You explain to Emma’s mother that there are lots of things that could be making her unwell so you’re going to send some tests to help work out what the problem is. You put in a cannula, take a gas, send some bloods to the lab and set her and her mother up to collect a urine.

Seeing that Emma has a metabolic acidosis on her gas you send a metabolic screen: plasma amino acids, urine organic acids, acylcarnitine profile. Her urine dip has some ketones but is otherwise unremarkable, except for a strange smell of sweaty feet…

Remembering a fabulous infographic about the importance of calculating the anion gap in children with a metabolic acidosis (and how to interpret them!), you get out your pen and paper and do the following calculations: 

Just as you’re pondering the causes of a raised anion gap, the lab phones with Emma’s blood results… Her ammonia is 184!

Emma has an acute neurological presentation, with metabolic acidosis, increased anion gap and mildly elevated ammonia, suggestive of an organic acidaemiaIn the context of a sick neonate with a raised anion gap, a normal lactate and normal ketones, think organic acids.

Are you familiar with ammonia?

A normal ammonia level is <50 mol/l but mildly raised values are common, up to 80 mol/l.

In neonates, any illness may be responsible for values up to 180 mol/l.

Artifactually high values can be caused by muscle activity, haemolysis or delay in separating the sample. Capillary samples are often haemolysed or contaminated and therefore should not be used.

There’s debate as to whether a level of >100 or 200 should be discussed with a metabolic specialist, but if in doubt, follow the RCPCH DeCon guideline and seek advice for any patient presenting with a level >100 mmol/l.

Urine organic acids and blood acylcarnitines will also be sent as part of this baby’s metabolic work-up. Although the results won’t be available in ED, the urine organic acid profile will confirm a diagnosis of an organic acidaemia, while the blood acylcarnitine profile will support the diagnosis as the organic acids conjugate with carnitines creating compounds such as isovalerylcarnitine.

The emergency treatment of suspected organic acidaemias

It’s important to think about your differentials. Sepsis is the most common – these conditions can mimic sepsis, or decompensation can be triggered by an infection, always cover with broad spectrum antibiotics. But don’t forget non-accidental injury and other differentials – the baby is likely to need a CT head if presenting encephalopathic or with seizures. If she continues to seize, load with an anticonvulsant.

 Specific emergency treatment of her metabolic presentation requires:

  • stopping sources of protein (milk)
  • avoiding catabolism (by giving glucose IV – 2mL/kg 10% glucose) 
  • rehydration (IV fluids resuscitation and maintenance)

What about that urine?

The “sweaty feet” smell of the urine points towards the diagnosis of Isovaleric Acidaemia. Remember that this condition can be part of the Newborn Screening in some countries (Ireland, UK, Australia, New Zealand).

Isovaleric acidaemia is a type of organic acidemia, inherited in an autosomal recessive way. It is caused by a problem with the enzyme that usually breaks down the amino acid leucine. This amino acid accumulates and is toxic at high levels, causing an ‘intoxication’ encephalopathy. The sweaty feet smell is stronger without treatment or  during acute exacerbations.

Maple Syrup Urine Disease (MSUD) is another organic acidaemia, associated with sweet smelling urine during decompensation. These children cannot break down leucine, valine and isoleucine. They may not have hypoglycaemia, hyperammonemia or acidosis and, if not picked up on newborn screening, can be diagnosed late, resulting in neurological sequelae.

Organic acidaemias: the take homes

  • Always measure the anion gap and send an ammonia sample in any sick neonate.
  • Sick neonates with metabolic acidosis, increased anion gap and mildly elevated ammonia may have an organic acidemia.
  • Treatment is to stop feeds, prevent catabolism with 10% dextrose (and standard electrolytes for IV maintenance) and cover for sepsis with IV antibiotics, whilst considering other differentials.

The next case feels like déjà vu…

The next baby you see is remarkably like Emma but with a subtle difference. Lucy is a 3 day old baby, presenting with poor feeding, irritability and seizures at home. There has been no fever, cough, coryza, or sick contacts. On examination she’s awake, extremely irritable, with upper limbs, extended lower limbs extended and global hyperreflexia. She has no dysmorphic features, cardiac murmur or abdominal organomegaly. You notice that she seems tachypnoeic at 70, although her lungs are clear. The rest of her observations are normal. 

The key differences between Emma and Lucy’s presentations is that Lucy is tachypnoeic and has a respiratory alkalosis; this should make you suspicious of hyperventilation. Always check an ammonia level in sick babies, but particularly in this case as hyperammonemia stimulates the brain stem respiratory centre, causing hyperventilation and, as consequence, respiratory alkalosis. 

The lab phones you with Lucy’s ammonia result…

Acute neurological presentations, with respiratory alkalosis and extremely elevated ammonia point towards a urea cycle disorder. Respiratory alkalosis is a common early finding caused by hyperventilation secondary to the effect of hyperammonemia on the brain stem, although later the respiratory rate slows as cerebral oedema develops and an acidosis is seen. Lucy also has a low urea and mildly deranged liver enzymes and INR, all of which support the diagnosis of a urea cycle disorder.

The emergency treatment of suspected urea cycle disorders

Overall the acute treatment is similar to the first case: cover for sepsis, manage seizures and consider differentials.

And as in the first suspected metabolic case:

  • stop sources of protein – stop feeds 
  • avoid catabolism – giving glucose IV – 2mL/kg 10% glucose 
  • rehydrate – IV fluids resuscitation and maintenance

In urea cycle disorders, the toxic metabolite is ammonia, so ammonia scavengers are used, all given intravenously:

  • sodium benzoate
  • phenylbutyrate 
  • arginine

A nice guideline on the management of hyperammonemia secondary to an undiagnosed cause can be found on the British Inherited and Metabolic Disease Group website.

Urea cycle disorders are autosomal recessive inborn errors of metabolism. A defect in one of the enzymes of the urea cycle, which is responsible for the metabolism of nitrogen waste from the breakdown of proteins, leads to an accumulation of ammonia as it cannot be metabolised to urea. The urea cycle is also the only endogenous source of the amino acids arginine, ornithine and citrulline.   The most common urea cycle disorder is Ornithine Transcarbamylase (OTC) deficiency. Unlike the other urea cycle disorders (which are autosomal recessive), OTC deficiency is x-linked recessive, meaning most cases occur in male infants. Female carriers tend to be asymptomatic.

CPSI: Carbomoyl Phosphate Synthetase; OTC: Ornithine Transcarbamylase; ASS: Arginosuccinate Acid Synthase; ASL: Arginosuccinate; ARG: Arginase

Classically, urea cycle disorders present in the neonatal period with vomiting, anorexia and lethargy that rapidly progresses to encephalopathy, coma and death if untreated. In these circumstances, ammonia accumulates leading to a very high plasma ammonia. 

Children presenting in infancy generally have less acute and more variable symptoms than in the neonatal period and include anorexia, lethargy, vomiting and failure to thrive, with poor developmental progress. Irritability and behavioural problems are also common. The liver is often enlarged but, as the symptoms are rarely specific, the illness is initially attributed to many different causes that include gastrointestinal disorders. The correct diagnosis is often only established when the patient develops a more obvious encephalopathy with changes in consciousness level and neurological signs. 

Adolescents and adults can present with encephalopathy and or chronic neurological signs. 

What are ammonia scavengers?

In urea cycle defects, ammonia cannot be converted to urea so instead is converted to glutamine and glycine. 

Ammonia scavengers phenylbutyrate and sodium benzoate offer alternative pathways for ammonia excretion through urinary pathways.

Phenylglutamine and hippurate are produced and are excreted in urine.

Urea cycle disorders: the take homes

  • Always measure the anion gap and send an ammonia sample in any sick neonate.
  • Sick neonates with respiratory alkalosis, normal anion gap and very elevated ammonia may have a urea cycle defect. 
  • Emergency treatment of urea cycle disorders is the same as for an organic acidaemia (stopping feeds, starting dextrose and rehydrating) PLUS intravenous ammonia scavengers.

Thank you to Dr Roshni Vara, Consultant in Paediatric Inherited Metabolic Disease at the Evelina London Children’s Hospital for her help with this post.

References

Adam , HH. Ardinger, RA. Pagon, S. E. Wallis, L. J. H. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews® [online book].

Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan;105(1):e10.

Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK.Arch Dis Child. 2006 Nov;91(11):896-9. 

Saudubray J-M, Baumgartner MR, Walter JH. (editors) Inborn Metabolic Diseases. Diagnosis and treatment. 6th Edition. Springer 2016. 

Bubble Wrap Plus July/August 2020

Bubble Wrap Plus – July/August 2020

Cite this article as:
Anke Raaijmakers. Bubble Wrap Plus – July/August 2020, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28628

Here is our bumper Bubble Wrap Plus, our monthly paediatric Journal Club List provided by Professor Jaan Toelen & his team of the University Hospitals in Leuven (Belgium). This comprehensive list of ‘articles to read’ 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 bubble wrap plus list features answers to intriguing questions such as: ‘Should we blame acid reflux for distress in infants?’, ‘Is there an association between enteric viruses and NEC?’, ‘Is there a value in US guided surfactant administration?’, ‘Do healthy children with a cervical lymph node need an ultrasound?’ and ‘Was there an outbreak of anorexia co-occurring with the pandemic?’.

1.Reviews and opinion articles

JULY HIGHLIGHTS

Ethical and Public Health Implications of Targeted Screening for Congenital Cytomegalovirus.

Gievers LL, et al. Pediatrics. 2020 Jun 26.

Reintroducing Dyslexia: Early Identification and Implications for Pediatric Practice.

Sanfilippo J, et al. Pediatrics. 2020 Jun 23.

Who has been missed? Dramatic decrease in numbers of children seen for child protection assessments during the pandemic.

Bhopal S, et al. Arch Dis Child. 2020 Jun 18.

The role of dietary fibre and prebiotics in the paediatric diet.

Boctor D. Paediatr Child Health. 2020 Jun;25(4):263-264.

Do facemasks protect against COVID-19?

Isaacs D, et al. J Paediatr Child Health. 2020 Jun;56(6):976-977.

To what extent do children transmit SARS-CoV-2 virus?

Isaacs D, et al. J Paediatr Child Health. 2020 Jun;56(6):978-979.

Should I be worried about carrying the virus that causes COVID-19 home on my clothes?

Howard-Jones A, et al. J Paediatr Child Health. 2020 Jun;56(6):980.

Maturation of glomerular filtration rate in neonates and infants: an overview.

Iacobelli S, et al. Pediatr Nephrol. 2020 Jun 11.

Microbiome in health and disease.

Giles EM, et al. J Paediatr Child Health. 2020 Jun 5.

Machine Learning and Artificial Intelligence in Pediatric Research: Current State, Future Prospects, and Examples in Perioperative and Critical Care.

Lonsdale H, et al. J Pediatr. 2020 Jun;221S:S3-S10.

Clinical Genomics in Critically Ill Infants and Children.

Raymond FL. JAMA. 2020 Jun 23;323(24):2480-2482.

AUGUST HIGHLIGHTS

Is Ileocolonoscopy Necessary When Evaluating Abdominal Pain and Nonbloody Diarrhea?

Sullivan JS, et al. Pediatrics. 2020 Jul 21:e20200699

Water fluoridation: current challenges.

Furness J, et al. Arch Dis Child. 2020 Jul 15:archdischild-2019-318545.

Isolated disproportionately raised alkaline phosphatase: Should we worry?

Lee YL, et al. J Paediatr Child Health. 2020 Jul 6.

Aplastic anaemia: Current concepts in diagnosis and management.

Furlong E, et al. J Paediatr Child Health. 2020 Jul;56(7):1023-1028

Little Doubt That CBT Works for Pediatric OCD.

Storch EA, et al. J Am Acad Child Adolesc Psychiatry. 2020 Jul;59(7):785-787.

Opioids or Steroids for Pneumonia or Sinusitis.

Phang KG, et al. Pediatrics. 2020 Jul 2:e20193690.

Diagnosis of rheumatic fever: the need for a better test.

Osowicki J, et al. Arch Dis Child. 2020 Jun 29:archdischild-2020-318970.

2. Original clinical studies

JULY HIGHLIGHTS

A randomized trial of parenteral nutrition using a mixed lipid emulsion containing fish oil in infants of extremely low birth weight: Neurodevelopmental outcome at 12 and 24 months corrected age, a secondary outcome analysis.

Thanhaeuser M, et al. J Pediatr. 2020 Jun 23.

Stop, think SCORTCH: rethinking the traditional ‘TORCH’ screen in an era of re-emerging syphilis.

Penner J, et al. Arch Dis Child. 2020 Jun 25.

Loop-mediated isothermal amplification for the early diagnosis of invasive meningococcal disease in children.

Waterfield T, et al. Arch Dis Child. 2020 Jun 25.

Incidence of SARS-CoV-2 vertical transmission: a meta-analysis.

Goh XL, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Jun 25.

Paediatric femur fractures-the value of contextual information on judgement in possible child abuse cases: are we bias?

Loos MHJ, et al. Eur J Pediatr. 2020 Jun 17.

Metabolic risk factors in children with kidney stone disease: an update.

Spivacow FR, et al. Pediatr Nephrol. 2020 Jun 20.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

Maisonneuve E, et al. J Pediatr. 2020 Jul;222:71-78.e6.

Ventilator-associated pneumonia in neonates: the role of point of care lung ultrasound.

Tusor N, et al. Eur J Pediatr. 2020 Jun 26.

Early Puberty and Telomere Length in Preadolescent Girls and Mothers.

Koss KJ, et al. J Pediatr. 2020 Jul;222:193-199.e5.

National Variations in Recent Trends of Sudden Unexpected Infant Death Rate in Western Europe.

de Visme S, et al. J Pediatr. 2020 Jun 22.

Parenting Interventions in Pediatric Primary Care: A Systematic Review.

Smith JD, et al. Pediatrics. 2020 Jun 24.

Risk Factors for Severe Anaphylaxis in Children.

Olabarri M, et al. J Pediatr. 2020 Jun 13.

Epileptic Spasms in Patients With Down Syndrome: Experiences From Caregivers.

Kats DJ, et al. J Child Neurol. 2020 Jun 25:883073820932770.

Antenatally detected urinary tract dilatation: a 12-15-year follow-up.

Herthelius M, et al. Pediatr Nephrol. 2020 Jun 23.

Nasal insertion depths for neonatal intubation.

Maiwald CA, et al.Arch Dis Child Fetal Neonatal Ed. 2020 Jun 22.

Body mass index rebound, weight gain in puberty, and risk of cardiovascular disease.

Arisaka O, et al. J Pediatr. 2020 Jun 19.

How to improve CPAP failure prediction in preterm infants with RDS: a pilot study.

Radicioni M, et al. Eur J Pediatr. 2020 Jun 19.

Reference values for the external genitalia of full-term and pre-term female neonates.

Castets S, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Jun 19.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

Shaikh N, et al. Pediatr Nephrol. 2020 Jun 15.

Ambulatory blood pressure abnormalities in children with migraine.

Yılmaz S, et al. Pediatr Nephrol. 2020 Jun 17.

Long-term follow-up of coronary artery lesions in children in Kawasaki syndrome.

Maccora I, et al. Eur J Pediatr. 2020 Jun 15.

Infant With SARS-CoV-2 Infection Causing Severe Lung Disease Treated With Remdesivir.

Frauenfelder C, et al. Pediatrics. 2020 Jun 18.

Reducing Abdominal Radiographs to Diagnose Constipation in the Pediatric Emergency Department.

Moriel G, et al. J Pediatr. 2020 Jun 14.

Cardiovascular Outcomes in Young Adulthood in a Population-Based Very Low Birth Weight Cohort.

Harris SL, et al. J Pediatr. 2020 Jun 14.

Early Use of Antibiotics Is Associated with a Lower Incidence of Necrotizing Enterocolitis in Preterm, Very Low Birth Weight Infants: Neomune-NeoNutriNet Cohort Study.

Li Y, et al. J Pediatr. 2020 Jun 14.

Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection: A Multi-institutional Study from New York City.

Kaushik S, et al. J Pediatr. 2020 Jun 14.

Reductions in Parent Interest in Receiving Antibiotics Following a 90-Second Video Intervention in Outpatient Pediatric Clinics.

Goggin K, et al. J Pediatr. 2020 Jun 15.

Growth curves: The experiences of Canadian paediatricians in their first 5 years of independent practice.

Schrewe B, , et al. Paediatr Child Health. 2020 Jun;25(4):235-240.

Pacifiers and the reduced risk of sudden infant death syndrome.

Smith RW, et al. Paediatr Child Health. 2020 Jun;25(4):205-206.

Improving HPV Vaccination Rates: A Stepped-Wedge Randomized Trial.

Perkins RB, et al. Pediatrics. 2020 Jun 15.

Parental Hesitancy About Routine Childhood and Influenza Vaccinations: A National Survey.

Kempe A, et al. Pediatrics. 2020 Jun 15.

Covid-19, Kawasaki disease, and Multisystem Inflammatory Syndrome in Children.

Bassareo PP, et al. J Pediatr. 2020 Jun 12.

Neonatal antibiotics and infantile colic in term born infants.

Kamphorst K, et al. J Pediatr. 2020 Jun 12.

Effect of Nonintervention vs Oral Ibuprofen in Patent Ductus Arteriosus in Preterm Infants: A Randomized Clinical Trial.

Sung SI, et al. JAMA Pediatr. 2020 Jun 15.

Typical RSV cough: myth or reality? A diagnostic accuracy study.

Binnekamp M, et al. Eur J Pediatr. 2020 Jun 13.

Validation of the Early Language Scale.

Visser-Bochane MI, et al. Eur J Pediatr. 2020 Jun 13.

Multicenter Analysis of Acquired Undescended Testis and Its Impact on the Timing of Orchidopexy.

Boehme P, et al. J Pediatr. 2020 Jun 9.

A Prospective Study of Costs Associated with the Evaluation of β-Lactam Allergy in Children.

Sobrino M, et al. J Pediatr. 2020 Jun 9.

Novel Coronavirus Infection in Febrile Infants Aged 60 Days and Younger.

McLaren SH, et al. Pediatrics. 2020 Jun 11.

Recurrent sudden unexpected death in infancy: a case series of sibling deaths.

Garstang JJ, et al. Arch Dis Child. 2020 Jun 11.

Polyethylene Glycol Dosing for Constipation in Children under 24 months: A Systematic Review.

Rachel H, et al. J Pediatr Gastroenterol Nutr. 2020 Jun 9.

The Role of the Placenta in Perinatal Stroke: A Systematic Review.

Roy B, et al. J Child Neurol. 2020 Jun 9:883073820929214.

Mental Health Problems and Risk of Suicidal Ideation and Attempts in Adolescents.

Orri M, et al. Pediatrics. 2020 Jun 8.

Primum non nocere: lingual frenotomy for breastfeeding problems, not as innocent as generally accepted.

Van Biervliet S, et al. Eur J Pediatr. 2020 Jun 6.

Group B Streptococcus Meningitis in an Infant with Respiratory Syncytial Virus Detection.

Barton MS, et al. J Pediatr. 2020 Jun 4.

Faecal calprotectin levels during the first year of life in healthy children.

Günaydın Şahin BS, et al. J Paediatr Child Health. 2020 Jun 5.

Parent-Child Agreement on Postconcussion Symptoms in the Acute Postinjury Period.

Gagnon I, et al. Pediatrics. 2020 Jun 4.

Does topical local anaesthesia reduce the pain and distress of nasogastric tube insertion in children?

Mort DO, et al. Arch Dis Child. 2020 Jul;105(7):697-700.

Effect of ondansetron on vomiting associated with acute gastroenteritis in a developing country: a meta-analysis.

Wu HL, Zhan X. Eur J Pediatr. 2020 Jun 3.

Comparison of the Prevalence of Infantile Colic Between Pediatric Migraine and Other Types of Pediatric Headache.

Levinsky Y, et al. J Child Neurol. 2020 Jun 3:883073820924264.

Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children’s Hospital in New York City, New York.

Zachariah P, et al. JAMA Pediatr. 2020 Jun 3:e202430.

Using Mobile Device Sampling To Objectively Measure Screen Use in Clinical Care.

Milkovich LM, et al. Pediatrics. 2020 Jun 1.

Young Children’s Use of Smartphones and Tablets.

Radesky JS, et al. Pediatrics. 2020 Jun 1.

Selection and Insertion of Vascular Access Devices in Pediatrics: A Systematic Review.

Paterson RS, et al. Pediatrics. 2020 Jun;145(Suppl 3):S243-S268.

Continuous Glucose Monitoring in Adolescent, Young Adult, and Older Patients With Type 1 Diabetes.

Agarwal S, et al. JAMA. 2020 Jun 16;323(23):2384-2385.

AUGUST HIGHLIGHTS

Anticonvulsant long-term and rescue medication: The children’s perspective.

Woltermann S, et al. Eur J Paediatr Neurol. 2020 Jul 14:

Chronic diarrhoea in children: A practical algorithm-based approach.

Shankar S, et al. J Paediatr Child Health. 2020 Jul;56(7):1029-1038

Transmission of SARS-CoV-2 by Children.

Merckx J, et al. Dtsch Arztebl Int. 2020 Jul 21;117(33-34):553-560.

Does selective evaluation of gastric aspirates in preterm infants influence time to full enteral feeding?

Kennedy L, et al. J Paediatr Child Health. 2020 Jul;56(7):1150-1154.

Severe motion sickness in infants and children.

Lipson S, et al. Eur J Paediatr Neurol. 2020 Jul 10:S1090-3798(20)30118-5

Risk Factors for Orthostatic Hypertension in Children.

Hu Y, et al. J Pediatr. 2020 Jul 12:S0022-3476(20)30873-8.

Distress in Infants and Young Children: Don’t Blame Acid Reflux.

Salvatore S, et al. J Pediatr Gastroenterol Nutr. 2020 Jul 6.

As soon as possible in IgE-cow’s milk allergy immunotherapy.

Boné Calvo J, et al. Eur J Pediatr. 2020 Jul 11.

COVID-19: minimising contaminated aerosol spreading during CPAP treatment.

Donaldsson S, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Jul 15:fetalneonatal-2020-319431.

A Comprehensive Clinical Genetics Approach to Critical Congenital Heart Disease in Infancy.

Shikany AR, et al. Pediatr. 2020 Jul 24:S0022-3476(20)30964-1

The association between enteric viruses and necrotizing enterocolitis.

Cheng C, et al. Eur J Pediatr. 2020 Jul 22

Intrauterine Device Use in Adolescents With Disabilities.

Schwartz BI, et al. Pediatrics. 2020 Jul 23:e20200016.

Social cognition and executive functions in children and adolescents with focal epilepsy.

Operto FF, et al. Eur J Paediatr Neurol. 2020 Jul 13:S1090-3798(20)30127-6.

Association Between Community Water Fluoridation and Severe Dental Caries Experience in 4-Year-Old New Zealand Children.

Schluter PJ, et al. JAMA Pediatr. 2020 Jul 27

Neurodevelopmental outcomes after moderate to severe neonatal hypoglycemia.

Helleskov AR, et al. Eur J Pediatr. 2020 Jul 14.

Associations of Birth Weight for Gestational Age with Child Health and Neurodevelopment among Term Infants: A Nationwide Japanese Population-Based Study.

Tamai K, et al. J Pediatr. 2020 Jul 5:S0022-3476(20)30829-5

Household Transmission of SARS-CoV-2 from Adults to Children.

Yung CF, et al. J Pediatr. 2020 Jul 4:S0022-3476(20)30852-0.

Use of Automated Office Blood Pressure Measurement in the Evaluation of Elevated Blood Pressures in Children and Adolescents.

Hanevold CD, et al. J Pediatr. 2020 Jul 4:S0022-3476(20)30762-9.

Coronary Dilatation and Endothelial Inflammation in Neonates born to mothers with Preeclampsia.

Lin IC, et al. J Pediatr. 2020 Jul 23:S0022-3476(20)30958-6.

Automated Office Blood Pressure Measurement for the Diagnosis of Hypertension.

Filler G, et al. J Pediatr. 2020 Jul 23:S0022-3476(20)30965-3

Effects of Neonatal Hyperglycemia on Retinopathy of Prematurity and Visual Outcomes at 7 Years of Age: A Matched Cohort Study.

Leung M, et al. J Pediatr. 2020 Aug;223:42-50.e2

Evaluation of Chest Radiographs of Children with Newly Diagnosed Acute Lymphoblastic Leukemia.

Smith WT, et al. J Pediatr. 2020 Aug;223:120-127.e3.

Delayed vs Immediate Cord Clamping Changes Oxygen Saturation and Heart Rate Patterns in the First Minutes after Birth.

Padilla-Sánchez C, et al. J Pediatr. 2020 Jul 22:S0022-3476(20)30902-1

Early surfactant replacement guided by lung ultrasound in preterm newborns with RDS: the ULTRASURF randomised controlled trial.

Rodriguez-Fanjul J, et al. Eur J Pediatr. 2020 Jul 24:1-8.

Lung ultrasound-guided surfactant administration: time for a personalized, physiology-driven therapy.

Raimondi F, de Winter JP, et al. Eur J Pediatr. 2020 Jul 24

Do otherwise well, healthy children with palpable cervical lymph nodes require investigation with neck ultrasound?

Paddock M, et al. Arch Dis Child. 2020 Jul 24:archdischild-2020-319648

Outbreak of anorexia nervosa admissions during the COVID-19 pandemic.

Haripersad YV, et al. Arch Dis Child. 2020 Jul 24:archdischild-2020-319868.

Frequency of Multifocal Disease and Pyogenic Arthritis of the Hip in Infants with Osteoarticular Infection in Three Neonatal Intensive Care Units.

Rubin LG, et al. J Pediatr. 2020 Jul 21:S0022-3476(20)30954-9.

Effect of Cognitive and Physical Rest on Persistent Post-Concussive Symptoms Following a Pediatric Head Injury.

Root JM, et al. J Pediatr. 2020 Jul 20:S0022-3476(20)30906-9

Celiac Disease in Children with Functional Constipation: A School Based Multicity Study.

Fifi AC, et al. J Pediatr. 2020 Jul 19:S0022-3476(20)30951-3.

Association between NICU Admission and Supine Sleep Positioning, Breastfeeding, and Postnatal Smoking among Mothers of Late Preterm Infants.

Hannan KE, et al. J Pediatr. 2020 Jul 19:S0022-3476(20)30952-5.

Test Strategies to Predict Inflammatory Bowel Disease Among Children With Nonbloody Diarrhea.

Van de Vijver E, et al. Pediatrics. 2020 Jul 21:e20192235.

Effect of cumulative dexamethasone dose in preterm infants on neurodevelopmental and growth outcomes: a Western Australia experience.

Buchiboyina AK, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Jul 20:fetalneonatal-2020-319147.

Predicting Nasal High-Flow Treatment Success in Newborn Infants with Respiratory Distress Cared for in Non-Tertiary Hospitals.

McKimmie-Doherty M, et al. J Pediatr. 2020 Jul 14:S0022-3476(20)30882-9.

Neonatal Candida auris infection: Management and prevention strategies – A single centre experience.

Chandramati J, et al. J Paediatr Child Health. 2020 Jul 16.

Flattening the (BMI) Curve: Timing of Child Obesity Onset and Cardiovascular Risk.

Armstrong S, et al. Pediatrics. 2020 Jul 6:e20201353

Body Mass Index From Early to Late Childhood and Cardiometabolic Measurements at 11 to 12 years.

Lycett K, et al. Pediatrics. 2020 Jul 6:e20193666

Parent Technology Use, Parent-Child Interaction, Child Screen Time, and Child Psychosocial Problems among Disadvantaged Families.

Wong RS, et al. J Pediatr. 2020 Jul 3:S0022-3476(20)30849-0

Being Mindful About Follow-up Care After Pediatric Hospitalization for Bronchiolitis.

Berry JG, et al. JAMA Pediatr. 2020 Jul 6:e201945.

Multivariate risk and clinical signs evaluations for early-onset sepsis on late preterm and term newborns and their economic impact.

Benincasa BC, et al. Eur J Pediatr. 2020 Jul 4.

Time to positive blood culture in early onset neonatal sepsis: A retrospective clinical study and review of the literature.

Marks L, et al. J Paediatr Child Health. 2020 Jul 3

Neonatal bacterial meningitis versus ventriculitis: a cohort-based overview of clinical characteristics, microbiology and imaging.

Peros T, et al. Eur J Pediatr. 2020 Jul 3

The utility of ketones at triage: a prospective cohort study.

Durnin S, et al. Arch Dis Child. 2020 Jul 3:archdischild-2019-318425.

Duration of Respiratory and Gastrointestinal Viral Shedding in Children With SARS-CoV-2: A Systematic Review and Synthesis of Data.

Xu CLH, et al. Pediatr Infect Dis J. 2020 Jun 30.

Clinical Severity of Gastroenteritis in Children Hospitalized With Rotavirus Infection Before and Post Introduction of a National Rotavirus Vaccination Program in Australia.

Clarke M, et al. Pediatr Infect Dis J. 2020 Jun 30.

Grasping Gaming: Parent Management Training for Excessive Videogame Use in Children.

Hughes T, et al. J Am Acad Child Adolesc Psychiatry. 2020 Jul;59(7):794-796.

Internet-Related Behaviors and Psychological Distress Among Schoolchildren During COVID-19 School Suspension.

Chen IH, et al. J Am Acad Child Adolesc Psychiatry. 2020 Jun 26:S0890-8567(20)30385-3.

Obesity is associated with severe clinical course in children with Henoch-Schonlein purpura.

Dundar HA, et al. Pediatr Nephrol. 2020 Jun 29.

Effect of opaque wraps for pulse oximeter sensors: randomised cross-over trial.

Kannan Loganathan P, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Jul 1:fetalneonatal-2020-319049.

E-cigarette Marketing Regulations and Youth Vaping: Cross-Sectional Surveys, 2017-2019.

Hammond D, et al. Pediatrics. 2020 Jul;146(1):e20194020.

Symptom Score: A New Instrument to Assess Orthostatic Intolerance in Children and Adolescents.

Cai H, et al. J Child Neurol. 2020 Jun 29:883073820936025.

Antibiotics for Childhood Pneumonia – Do We Really Know How Long to Treat?

Chang AB, et al. N Engl J Med. 2020 Jul 2;383(1):77-79.

Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children.

Ginsburg AS, et al. N Engl J Med. 2020 Jul 2;383(1):13-23.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

Feldstein LR, et al. N Engl J Med. 2020 Jul 23;383(4):334-346.

Childhood Multisystem Inflammatory Syndrome – A New Challenge in the Pandemic.

Levin M. N Engl J Med. 2020 Jul 23;383(4):393-395.

3. Guidelines and Best Evidence

JULY HIGHLIGHTS

Perineal Groove: An Anorectal Malformation Network, Consortium Study.

Samuk I, et al. J Pediatr. 2020 Jul;222:207-212.

The Implementation of Screening for Adverse Childhood Experiences in Pediatric Primary Care.

DiGangi MJ, et al. J Pediatr. 2020 Jul;222:174-179.e2.

Helicobacter Pylori Infection in Pediatric Patients Living in Europe: Results of the EuroPedHP Registry 2013-2016.

Kori M, et al. J Pediatr Gastroenterol Nutr. 2020 Jun 11.

Updated Strategies for Pulse Oximetry Screening for Critical Congenital Heart Disease.

Martin GR,  et al. Pediatrics. 2020 Jun 4.

AUGUST HIGHLIGHTS

Barrier Protection Use by Adolescents During Sexual Activity.

Grubb LK; COMMITTEE ON ADOLESCENCE. Pediatrics. 2020 Jul 20:e2020007237.

Long-Acting Reversible Contraception: Specific Issues for Adolescents.

Menon S; COMMITTEE ON ADOLESCENCE. Pediatrics. 2020 Jul 20:e2020007252.

Nasal swab as preferred clinical specimen for COVID-19 testing in children.

Palmas G, et al. Pediatr Infect Dis J. 2020 Jul 1.

What is the effectiveness and safety of different interventions in the management of drooling in children with cerebral palsy?

Khajuria S, et al. Arch Dis Child. 2020 Jun 30:archdischild-2020-319309

4. Case Reports

JULY HIGHLIGHTS

A case of cannabinoid hyperemesis syndrome highlighting related key paediatric issues.

Leveille CF, et al. Paediatr Child Health. 2020 Jun;25(Suppl 1):S7-S9.

New Onset Chorea in a Previously Healthy 7-Year-Old.

Delaney MA, et al. J Pediatr. 2020 Jun 10.

An 8-Year-Old Boy With Fever, Splenomegaly, and Pancytopenia.

Offenbacher R, et al. Pediatrics. 2020 Jun 12.

Case 5-2020: A 32-Day-Old Male Infant with a Fall.

Rothstein P.  N Engl J Med. 2020 Jun 11;382(24):2381.

Elevated Serum Creatinine: But Is It Renal Failure?

Wong Vega M, et al. Pediatrics. 2020 Jun 17.

AUGUST HIGHLIGHTS

Rare cutaneous manifestations of parvovirus B19 infection in a child.

Yan J, et al. J Paediatr Child Health. 2020 Jul 28. doi: 10.1111/jpc.15030.

A Toddler with Sudden Scrotal Swelling.

Trombetta A, et al. J Pediatr. 2020 Aug;223:220-221

Evolving Peri-Anal Mass in 2-Year-Old.

Yang A, et al. Pediatr Infect Dis J. 2020 Jun 16.

Myocarditis in a 16-year-old boy positive for SARS-CoV-2.

Gnecchi M, et al. Lancet. 2020 Jun 27;395(10242):e116

Case 20-2020: A 7-Year-Old Girl with Severe Psychological Distress after Family Separation.

Gartland MG, et al. N Engl J Med. 2020 Jun 25;382(26):2557-2565.

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

The 42nd Bubble Wrap

Cite this article as:
Leo, G. The 42nd Bubble Wrap, Don't Forget the Bubbles, 2020. Available at:
https://dontforgetthebubbles.com/the-42nd-bubble-wrap/

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: Vitamin A, B, C…. knowing when to prescribe is not as easy as 1, 2, 3!