PEM adventures chapter 4

Cite this article as:
Team PEM Adventures. PEM adventures chapter 4, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33252
Miserable child with asthma

Meet Jasmine, a 23-month-old girl with a background of recurrent viral-induced wheeze. Today, she’s come in with a three-day history of coryzal symptoms and has been struggling with her breathing since this morning. Her mum had been giving 10 puffs of salbutamol at home but it didn’t seem to be making much difference so she’s brought her into your Paediatric ED.

On examination, Jasmine looks pale. There’s a scattered wheeze and a few basal crepitations. She has moderate abdominal breathing with some associated tracheal tug.

Her observations are up:

Ouch, you don’t like the look of those oxygen saturations. She’s not that wheezy, but you wonder if she will open up with a bronchodilator and is currently too tight for you to hear much wheeze.  

You pop on high flow oxygen at 15 L/min but what do you prescribe?

The oxygen brings Jasmine’s sats up to 95%, her colour improves a little but she continues to work hard with her breathing.

BTS 2019 asthma guidelines

You know the BTS/Sign guideline suggests children over 1 year may benefit from asthma medications and she has responded before. Looking at her observations, you decide Jasmine fits a picture of Acute Severe wheeze and decide to try a single dose of salbutamol then reassess for a response.

The oxygen brings Jasmine’s sats up to 95%, her colour improves a little but she continues to work hard with her breathing.

BTS asthma severity

Looking at her observations, you decide Jasmine fits a picture of Acute Severe wheeze as per the BTS/SIGN guidance and prescribe a burst of 3 back-to-back salbutamol nebulisers with ipratropium added to the first. She is quite young, but you know she’s been wheezy with coughs and colds before.

While these are running through you pick up an ankle injury that you can see quickly and ask Jasmine’s nurse to repeat her observations when she has completed treatment.

The oxygen brings Jasmine’s sats up to 95%, her colour improves a little but she continues to work hard with her breathing.

BTS asthma severity

Looking at her observations, you decide Jasmine fits a picture of Acute Severe wheeze as per the BTS/SIGN guidance and this is the most likely diagnosis since she has been wheezy with cough and colds before.

However, she’s still young and you don’t want to overdo the beta-agonists, so you decide to prescribe a single salbutamol nebuliser and review her response 15 minutes later.

As you are about to pick up the next card, some of the medical students you’ve worked with before ask if they can follow the case with you. “We’ve barely seen any wheezy kids in our whole placement,” they say. “Of course,” you reply, “but we’ve barely seen any during the pandemic either… I might need your help remembering how to treat her!”

You recap the case for them and explain what treatment you have decided to give first.

“Wouldn’t you ever use nebulised magnesium in a case like this?” one of the students asks. “I am sure I read that the BTS/Sign guideline suggests it for all children with sats of less than 92% at presentation?”

You pull the guideline up on your phone.

They’re right. However, you’ve never done this in practice. As far as you remember the evidence around nebulised magnesium is mixed.

In 2013 the Lancet published the results of the MAGNETIC trial.

This, you explain, was an RCT designed to compare standard acute asthma treatment with standard treatment plus nebulised magnesium sulphate. 500 children aged 2-16 years with acute severe asthma were randomised to receive either nebulised magnesium sulphate in addition to salbutamol or placebo plus salbutamol. They found no difference in the asthma severity score at 60 minutes post randomisation. However, they did note, that magnesium made more difference to those with more severe symptoms at presentation and a short duration of wheeze.

Following this there was some enthusiasm for giving magnesium to children with short duration of severe wheeze, but, you continue, it’s never really caught on. Last year, a large study of over 800 2 to 17 year olds with acute wheeze, showed absolutely no benefit of magnesium sulphate over placebo: there was no difference in hospitalisation within 24 hours or change in asthma severity score at four hours. “So, in answer to your question,” you tell the students, “it’s probably not going to make much difference here.”  

As you finish explaining, Jasmine’s nurse comes in to find you. ”Can you come and review Jasmine please?” she asks. “She’s not looking too great.”

And she’s right, in fact Jasmine barely looks any better than when she arrived. She is more tachycardic and feels cool at her hands and feet. She is still recessing, a bit less wheezy, and the oxygen saturations, in 15L, are sitting at 96%.

Observations forchild with asthma

Hmmm… you think to yourself… she needs another neb and if she doesn’t improve after that we’ll have to escalate things…

While Jasmine’s nurse gets the next nebuliser ready, you wonder whether a dose of steroids wouldn’t go amiss. At almost two years old, with a history of similar episodes, this sounds like a case of viral induced wheeze to you.

You know from Foster’s 2018 trial, that in children with pre-school wheeze, steroids made no difference to acute change in respiratory score or time to ED discharge. The key benefit they showed was reduction of length of hospital stay amongst children who were admitted.

This could be Jasmine. But you’re not sure which way she’s going yet… So what do you prescribe?

You prescribe a dose of oral prednisolone – which Jasmine promptly vomits.

If only your hospital was using dexamethasone these days.

You know that the original trial by Cronin and colleagues showed no significant difference in day 4 respiratory score or unscheduled reattendance when they compared dexamethasone to prednisolone for wheezing children aged 2-16. And there seems to be a growing evidence base to support these findings. Unfortunately, the most recent systematic review you’ve read was underpowered to draw strong conclusions. Although one thing was pretty clear – children with wheeze are far less likely to vomit after dexamethasone compared to prednisolone.

You go back and select again…

You’ve read up a bit on the evidence around this, and know that the original trial by Cronin and colleagues showed no significant difference in day 4 respiratory score or unscheduled reattendance when they compared dexamethasone to prednisolone for wheezing children aged 2-16. This finding has been replicated in many subsequent trials as Wei and colleagues summarise in their recent systematic review. Although the review was underpowered to draw strong conclusions, there was one thing they were pretty clear on – kids are hands down less likely to vomit after dexamethasone compared to prednisolone. Jasmine tolerates the dex just fine.

You’d rather not start the steroids just yet.

Jasmine is only 23 months old. You know she’s been wheezy before but this could still be bronchiolitis.

As far as you remember, the greatest benefit of prednisolone for pre-schoolers is supposed to be amongst those admitted to hospital, when oral prednisolone will reduce time to hospital discharge. So, you hold off for now thinking that you can always give a dose later.

It’s time for a clinical review. But Jasmine looks worse. She is still tachycardic, a bit mottled, wheeze is unchanged and she’s more tachypnoeic.

Observations for child with asthma

“She’s not responding,” you say. “We’re going to need an IV bronchodilator after all.”

You insert a line for IV treatment and take a gas and a few other bloods while you are at it. You decide to make your consultant aware that Jasmine is looking pretty sick. They agree she needs an IV bronchodilator and will pop down to review straight away.

You sit down to prescribe her treatment…

But what drug are you going to give?

You decide to give IV salbutamol as your first line agent

You recently read a large Cochrane review on second-line treatments for acute asthma. It was published last year and included 67 trials from 13 different Cochrane reviews dated up to the end of December 2019 (7). You don’t remember all the details but you do remember that NO single IV agent had been shown to reduce rates of escalation to PICU.

Jasmine is very tachycardic, but she’s also borderline hypotensive so on balance you decide this will be a better option than magnesium. The BTS guidelines suggest either salbutamol or magnesium can be used as first-line IV agent and you feel it’s the right choice in this particular scenario.  

You type up the script and ask Jasmine’s nurse to get it ready as quick as she can.

You decide to give IV magnesium as your first line agent.

You recently read a large Cochrane review on second-line treatments for acute asthma. It was published last year and included 67 trials from 13 different Cochrane reviews dated up to the end of December 2019. You don’t remember all the details but you do remember that NO single IV agent had been shown to reduce rates of escalation to PICU. Magnesium sulphate is your go-to IV drug for refractory wheezers, its recommended in the BTS guidelines and it hasn’t let you down so far.

You type up the script and ask Jasmine’s nurse to get it ready as quick as she can.

You decide to give aminophylline as your first line agent.

But your nurse in charge is reluctant. “We don’t typically use this first-line” he says…and it’s true, you don’t prescribe it often. You recently read a large Cochrane review on second-line treatments for acute asthma. It was published last year and included 67 trials from 13 different Cochrane reviews dated up to the end of December 2019. You don’t remember all the details but you do remember that NO single IV agent had been shown to reduce rates of escalation to PICU.

Your nurse in charge had read the same review and reminded you that it also found vomiting to be more common with aminophylline.

OK, we’ll go with magnesium then,” you say, it shouldn’t make too much of a difference –  she just needs something fast.

Finally, the infusion is up and running. You decide now is a good moment to grab a round of coffees for the team. But, to your horror, whilst standing in the queue, the crash buzzer goes off… you sprint back to the department wondering who on earth it can be for…

…and arrive to find Jasmine having CPR.

Jasmine turned pale after the infusion started, became more tachycardic, then hypotensive and then crashed.

The play specialist is crying as she thinks she overstimulated her with the bubbles. “It’s not that,” you reassure her, “I think we must have missed something here.”

But despite a sterling resuscitation and the team’s best efforts, Jasmine does not survive. Fortunately for you, this is not real life, it’s a PEM adventure and so we get to go back in time…..

And THIS time, you’re handed the gas before you write up the IV bronchodilator.

Oh rats,” you think. Tachycardia, hypotension, raised lactate. This must be sepsis. Hastily you prescribe 80mg/kg ceftriaxone and a 20ml/kg saline bolus.

But to your dismay this just puts Jasmine’s heart rate up even further.

At that moment your consultant arrives.

“Hmm… calcium’s a bit low,” they say.

Your mind is racing… why is the calcium low? Her lactate, her tachycardia, her poor response to bronchodilators and fluid is all starting to feel decidedly cardiac to you.

Jasmine starts to look drowsy and a worrying shade of pale. You order a portable CXR and your consultant suggests a dose of calcium gluconate – just in case. As all this is being organised, you recap the story so far.

“This is 23 month-old Jasmine. She presented with three days of coryzal illness followed by difficulty in breathing and wheeze. She’s had an oxygen requirement since she got here and was working hard with mild wheeze on auscultation. We gave salbutamol nebulisers plus ipratropium and a dose of steroids with little effect on her tachypnoea. She’s been here for about an hour and a half and has become more tachycardic, with a poor gas. We were about to give an IV bronchodilator,” you explain, “but with that gas I am really concerned we are missing something.”

Together you and your consultant re-examine Jasmine. She’s pale, peripherally mottled and tachycardic. Her BP is holding at 75 systolic. Her heart sounds are so fast you can’t tell if there’s a murmur or not. Her peripheral pulses are thready and those basal creps are now worse. Her liver is palpable 5cm below the costal margin

“Its got to be cardiac,” you conclude. “Shall we get her round to resus?”

Round in resus you pull up Jasmine’s x-ray. Her lungs look a little wet to you.

CXR of child with myocarditis

And it all starts to make sense. No wonder she didn’t get better with salbutamol – it never was bronchial asthma in the first place. It must have been cardiac wheeze secondary to rapid onset pulmonary oedema. “This must be a cardiomyopathy or myocarditis,” you say out loud. You know you know you need to support Jasmine’s sick myocardium with a vasoactive agent and fast.

But which one are you going to choose?

Adrenaline – a potent beta-agonist with alpha activity at higher doses; increases heart rate and contractility; good for low cardiac output states. “Yes, this would work here” your boss agrees..

Great choice. Time to move on.

Noradrenaline – a potent alpha-agonist with beta-agonist activity at higher doses; noradrenaline increases systemic vascular resistance by vasoconstriction and is good for distributive shock.

Hmmm…no, not norad” advises your consultant…

Try again

Milrinone – an inodilator that induces positive inotropy through phosphodiesterase inhibition, but simultaneously decreases systemic vascular resistance;  good for low cardiac output states. “This could work” your boss agrees, but they have never used it in ED before. Hmmmm…maybe not the best choice for now.

 Try again

Dopamine – a dopamine and adrenoreceptor agonist with dose dependent effects: inotropy at lower doses, vasoconstriction at higher doses; and additional effect to promote aldosterone secretion. At least you know how to give this peripherally, but you are not sure it’s the best option for Jasmine.

Try again

Dobutamine – an alpha and beta-agonist that produces increased myocardial contractility with little effect on heart rate and systemic vascular resistance; good for low cardiac output states. This could work, although you barely ever use it.

We can get some advice from our retrieval team” suggest your consultant “but I don’t think is the best choice for Jasmine”.

Try again

You call the local cardiac centre who agree, Jasmine should be treated as having cardiogenic shock and suggest that starting a peripheral or IO adrenaline infusion at 0.01mcg/kg/min is the safest first line option.

“What about milrinone?” you ask. They explain that they would prefer to wait until Jasmine’s BP is more stable as milrinone can vasodilate before it starts to work as an inotrope. It’s best given, they advise, once she’s safely arrived at their end and had an echo to confirm the diagnosis.

They would like you to intubate to reduce myocardial demand once the adrenaline infusion is up and request immediate transfer to their unit – no more fluid boluses. In fact, they suggest, have adrenaline boluses ready for intubation: draw up the arrest dose into a 10 ml syringe and dilute with saline so it can be given in 1ml aliquots at a tenth of the arrest dose to support the BP if needed.

If possible put in an arterial line, or at the very least cycle the BP every minute. Oh and of course, don’t forget an ECG.

Jasmine is successfully intubated for transfer using ketamine, rocuronium and fentanyl in a 1:1:1 ratio.

As you finally sit down to write some notes, the medical students from earlier approach.

“This has been fascinating,” they say. “We’d like to present this case at grand rounds. Myocarditis: the master of disguise. And we found this great paper…”

Freedman et al. Pediatric myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics 120; 6:1278-85 December 2007 

Freedman and colleagues performed a retrospective review of paediatric patients who attended the Hospital for Sick Children in Toronto with myocarditis between May 2000 and May 2006. There were 16 cases of definite (biopsy-proven) myocarditis and 15 cases of probable myocarditis. And when looked at the demographics of the sample they found a few interesting things:

  • Age was not normally distributed, with peaks among children under three years and over 16 years of age
  • In their cohort:
    • 32% presented with predominantly respiratory symptoms
    • 29% had cardiac symptoms
    • 6% had gastrointestinal symptoms  
    • But this was significantly associated with age
  • Half of under 10’s had primarily respiratory symptoms
  • None of the under ten’s had cardiac symptoms or chest pain at presentation
  • The two children with gastroenteritis symptoms were also under ten.
  • Initial misdiagnosis with pneumonia or asthma happened in 57% of cases.
  • 25% of children were admitted with a different diagnosis to begin with.

This starts to make you feel a little better.

“But it’s not only symptoms that can be misleading,” the students continue. The paper looked at the relevance of investigations too:

  • Just over (55%) half of initial chest x-rays were abnormal.
  • Typical signs when present included cardiomegaly, pulmonary venous congestion and pleural effusion.
  • ECG was more sensitive with 93% abnormal at presentation

Signs included: ST or T wave abnormalities, axis deviation, ventricular hypertrophy, infarction pattern, decreased voltage, atrial enlargement and AV block.

  • Aside from troponin (which wasn’t assessed as it was measured at presentation in less than 30% patients), AST was the most useful biomarker for potential myocarditis and a value over 100 U/L was significantly associated with cardiac disease

Well, you think to yourself as Jasmine leaves the building with the retrieval team, sick but more stable, every day’s a school day. As you reflect on the biases influencing your decision making through Jasmine’s ED journey, you remind yourself to keep a more open mind in the future. And you save the date in your diary for the medical student’s grand round presentation.

Jasmine makes a complete recovery and one year later comes to visit you in PED. She and her Mum have been busy fundraising and she is here, full of 3 year old attitude, ready to donate the proceeds to your department.

But before we go, lets hop back in that PEM adventures time machine one more time and see what was the learning from Jasmine’s case.

Nebulised MgSO4

The MAGNETIC trial in 2013 was an RCT designed to compare standard acute asthma treatment with standard treatment plus nebulised magnesium sulphate (2).

Powell, C., Kolamunnage-Dona, R., Lowe, J., Boland, A., Petrou, S., Doull, I., Hood, K., Williamson, P. and MAGNETIC Study Group, 2013. Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial. The Lancet Respiratory Medicine, 1(4), pp.301-308.

They randomised 500 children aged 2-16 years with acute severe asthma to receive either nebulised magnesium in addition to salbutamol or salbutamol plus placebo. They found no difference in the asthma severity score at 60 minutes post randomisation. However, they did note that magnesium made more difference to those with more severe symptoms at presentation and a short duration of wheeze.

Last year, a large multicentre Canadian study of over 800 2-17-year-olds with acute wheeze (3) showed absolutely no benefit of magnesium sulphate over placebo. They randomised children with persistent signs of moderate to severe wheeze after initial treatment with three albuterol and ipratropium nebulisers and steroids to receive either magnesium sulphate or placebo to be administered alongside three further albuterol nebulisers.  The primary outcome measure for this study was hospitalisation within 24 hours. They found no difference between groups in hospitalisation or change in asthma severity score at 4h post-treatment.

So, although the BTS guideline still does recommend this, in practice its not used widely in UK emergency departments and although it’s unlikely to do harm, it probably won’t make a huge difference to the patient in front of you.

Steroids for preschool wheeze

Two well-known studies on this topic are those by Foster in 2018 (4) and Panickar in 2009 (10) and for a great discussion on these have a read of this DFTB blog (11)

Panickar, J., Lakhanpaul, M., Lambert, P.C., Kenia, P., Stephenson, T., Smyth, A. and Grigg, J., 2009. Oral prednisolone for preschool children with acute virus-induced wheezing. New England Journal of Medicine360(4), pp.329-338.

In 2009, Panickar and colleagues performed a double blind RCT in children aged 10-60 months with acute virus induced wheezing across three UK centres (10). They randomised 700 children to receive a 5-day course of either prednisolone or placebo after initial albuterol treatment and measured the PRAM score at 4 hourly intervals from enrolment to hospital discharge.

Their primary outcome measure was duration of hospital stay and the trial found no significant difference between groups on this measure. There was also no difference in PRAM scores at any time interval or readmission within 1 month. And this held even when performing a subgroup analysis of children at higher risk of an atopic asthma phenotype. Of course, the caveat to this study, is the age range included in the trial. Infants in the ten months to 2 years age group show a degree of heterogeneity in disease phenotype; many will have a bronchiolitic illness rather than an inflammatory viral induced wheeze and respond differently to steroid medication (12).

Foster, S.J., Cooper, M.N., Oosterhof, S. and Borland, M.L., 2018. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine6(2), pp.97-106.

Foster and colleagues performed a similar trial in 2018 (4) randomising 600 children aged 24-72 months presenting with virus-associated wheezing, to receive prednisolone or placebo. They chose this age range specifically to avoid the confusion of including patients with bronchiolitis in the sample.

They also found that steroids made no difference to acute change in respiratory score or time to ED discharge. However, amongst children who were admitted to hospital, total length of stay in the steroid group was reduced. There was no difference in re-attendance or PICU admission but of note, children with the most severe symptoms or co-morbidities at presentation (for example, oxygen saturations <92% in air; a silent chest; shock or sepsis; previous PICU admission with wheeze; prematurity; other cardiac or respiratory disease) were excluded. So for this group, which would certainly include Jasmine, the question perhaps remains unanswered.

Wallace, A., Sinclair, O., Shepherd, M., Neutze, J., Trenholme, A., Tan, E., Brabyn, C., Bonisch, M., Grey, N., Johnson, D.W. and McNamara, D., 2021. Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial. Archives of Disease in Childhood106(4), pp.339-344.

A further trial, published last year by Wallace and colleagues (13), randomised 493 children aged 24-59 months to receive either prednisolone or placebo. They found no difference between groups in the primary outcome measure – change in baseline PRAM score at 24 hours and 7 days. However, they noticed with interest, that the median PRAM score at 24 hours was zero in both groups with only a small number of children remaining symptomatic at this time point.  This they argue, illustrates how viral-induced wheezing attacks may often be short-lived in nature and the most important benefits of steroids, if any, must occur within that initial 24-hour period.

Within the first 24 hours, they did find some benefit of prednisolone over placebo: those in the prednisolone group had significantly lower PRAM scores 4 hours after medication administration which translated into a reduced requirement for hospital admission, additional steroid or intravenous treatment. A particular strength of this study was the analysis of several subgroups for salbutamol responsiveness, positive Asthma Predictive Index and baseline severity. The subgroup analysis showed that the primary outcome measure (PRAM score at 24 hours and 7 days) was not modified by any of these factors, however, the analysis was not extended to the secondary outcomes (ie what happened within those first 24 hours).

This is a shame as it is increasingly well recognised that several different wheezing phenotypes exist and that these may determine response to standard asthma therapies. Ultimately, the answers we are looking for may come from studies such as the DOORWAY (Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth) (14) project. This exciting study aims to identify genetic determinants of responsiveness to steroids so that one day clinical management can be better individualised.

Dexamethasone or prednisolone?

This is an interesting question that has been raised within the PEM community in recent years. Early studies show single dose dexamethasone is non inferior to a 3 day course of oral prednisolone for children attending ED with wheeze. It sorts out the respiratory symptoms, is overwhelmingly less likely to get vomited up and doesn’t need to be given by parents for two further days at home.

For example, the original trial by Cronin and colleagues showed no significant difference in day 4 respiratory score or unscheduled reattendance when they compared dex to pred for wheezing children aged 2-16 (5). This finding has been replicated in many subsequent trials as Wei and colleagues summarise in their recent systematic review (6).

Wei and colleagues looked at 7 trials comparing dexamethasone to prednisolone for the treatment of acute wheeze , specially aiming to compare relapse rates and adverse effects. Six out of the seven trials included children from age 2 to adult – avoiding the inclusion of those with potential bronchiolitis, but clearly including a mix of both atopic asthmatics and those with viral induced pre-school wheeze.  

Wei and colleagues found no significant difference between dexamethasone and prednisolone on relapse rate up to five days post treatment or 10-15 days of follow-up and this held whether children received one or two doses of dexamethasone. There was no difference in hospital readmission rates or adverse events between the two drugs, however the incidence of vomiting both in hospital and at home was significantly higher in the prednisolone group.

Sounds like a no-brainer then? Unfortunately, not quite. Conscious of the relatively small number of quality trials conducted on this topic, Wei and colleagues conducted a power calculation to determine the validity of their results. This showed the meta-analysis was underpowered to accurately answer the questions posed. Whilst their results are suggestive that dexamethasone is at least equivalent to prednisolone, they caution that further and larger studies on the topic are required before strong conclusions can be drawn.  In addition, further studies should try to differentiate dexamethasone response between pre-school wheezers and those with a more atopic phenotype as anecdotal evidence suggest there is likely to be a difference between these two groups.

Again, this is all going to come back to findings of projects such as DOORWAY which should one day help us to provide more nuanced care.

IV bronchodilators

Despite the fact that an acute exacerbation of wheeze or asthma represents the bread and butter of acute paediatrics, we have a yet to achieve consensus for the best way in which to treat it.  It is widely accepted that inhaled bronchodilators and steroids are the best first-line approach, but there are several options for second line IV treatment (IV beta-agonists, IV adrenaline, IV magnesium sulphate, IV methylxanthines and IV ketamine) and no evidence with which to separate them. A few years ago PERUKI conducted a survey to establish prescribing practices for second line asthma treatments amongst senior UK based ED clinicians (15) and this clearly illustrated wide variation in practice around the UK. Magnesium sulphate was the most frequently prescribed first IV infusion but this was by no means universal.

Last year a Cochrane review of systematic reviews on treatments for asthma (7) was conducted, the aim being to try and unravel the story here a little better. They included 13 Cochrane Systematic Reviews on various treatment options for acute asthma. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. Four of the 13 reviews focussed on IV medication although none compared all three big players (beta agonists, magnesium sulphate and methylxanthines) head-to-head. No single agent was identified as being able to reduce risk of ITU admission. And no one single agent appeared markedly superior to the others for any of the primary outcome measures.

What we need, is a well-designed and adequately powered, large scale RCT to directly compare the three most commonly used IV bronchodilator treatments, including subgroup analyses in preschool and school‐aged children, and for varying degrees of asthma severity.

Myocarditis

This case was a great illustration of the difficulties that can arise in the early identification of acquired cardiac pathology, particularly in younger children who do not tend to complain of cardiac symptoms and may present with a predominantly respiratory or non-specific picture. The key to diagnosis is recognising when there is a lack of expected response to treatment and picking up on the small signs that can give the game away. The astute amongst you may have noticed Jasmine’s unusually wide pulse pressure at presentation. Perhaps, if you had been the doctor examining, you’d have felt for the liver a little earlier on too?

From a PED management perspective the key to success is firstly in recognising the problem and getting early expert advice.

Myocarditis has been defined as an “inflammatory disease of the heart muscle” and has a variable clinical presentation, with several distinct disease phenotypes (16). As in Jasmine’s case, it is commonly viral in origin (think enterovirus/coxsackie/adenovirus and parvovirus). But there are some other important differentials to consider as well:

  • Familial Cardiomyopathy/metabolic
  • Cardiac Structural abnormality (ALCAPA/Coarctation)
  • Idiopathic dilated cardiomyopathy
  • Hypocalcaemia and Vitamin D deficiency (8)

Classic myocarditis may have a relatively insidious onset with worsening fatigue and exertional dyspnoea or in older teenagers may mimic an acute coronary syndrome. It is associated with echocardiographic findings of left ventricular dilatation (which may be indistinct from a dilated cardiomyopathy picture), reduced ejection fraction, segmental wall abnormalities +/- pericardial effusion (16).

Fulminant myocarditis is a distinct symptom complex, and when supportive care is administered in a timely fashion, typically enjoys a higher rate of complete recovery of function. It may present with a history of recent viral illness followed by sudden-onset heart failure usually within 2-4 weeks and usually has more severe ventricular dysfunction. In contrast to classic myocarditis, it has an echocardiographic phenotype of reduced left ventricular ejection, normal left ventricular cavity size, and increased septal thickening.

Fulminant myocarditis conversely is a distinct symptom complex. It typically follows a viral illness and presents with sudden onset heart failure as in our case above. Echocardiographic findings typically show reduced left ventricular ejection, normal left ventricular size and increased septal thickening. Heart size on chest x-ray may not be hugely increased (16). Provided appropriate supportive measures are initiated early, long-term prognosis is often better in this group (16).

Management – both in ED and PICU – is predominantly supportive.

Inotropes are the best way to support the child, like Jasmine, presenting in cardiogenic shock. And heart failure should be managed according to published guidelines once the child is stabilised (17). Adrenaline is recommended as a first line infusion where there is evidence of hypotension and poor end organ perfusion. Milrinone and/or dobutamine are of benefit once BP has stabilised (17). The child should be intubated and ventilated but make sure you’ve gone through your intubation checklist and be prepared for a bumpy ride as these patients are notoriously unstable and will arrest with even slight changes to their compensatory physiology.

Despite much debate and equivocal evidence of benefit (18), in PICU Jasmine received a dose of IVIG and over the course of 10 days was gradually weaned off milrinone.  She made an excellent recovery with a return to normal ventricular function 6 months later. Unfortunately, many children are not as lucky and will require ECMO – either as rescue therapy or as a bridge to transplant.

Jasmine was 23 months old, but for children under 10kg ECMO as a bridge is problematic, both ethically and clinically: there’s a small pool of eligible hearts and ECMO is a finite resource.  The answer may be a left ventricular assist device, where there have been growing reports of success, including amongst the very young (19) … but that’s for another PEM adventure.

References

  1. SIGN158 British guideline on the management of asthma: A national clinical guideline. First published 2003 Revised edition published July 2019
  2. Powell et al. Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised controlled trial.  The Lancet Volume 1; 4: 301-308 June 2013
  3. Scuh at al. Effect of nebulized magnesium vs placebo added to albuterol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized controlled trial. JAMA. 2020;324(20):2038-2047.
  4. Foster et al.  Oral prednisolone in pre-school children with virus-associated pre-school wheeze: a prospective, double blind, randomised controlled trial. The Lancet. Volume 6, Issue 2. P97-106. February 2018.
  5. Cronin et al.  A randomized controlled trial of single dose oral dexamethasone versus multi-dose oral prednisolone for acute exacerbations of asthma in children who attend the emergency department.  Annals of Emergency Medicine: 67;5: 503-601 2016
  6. Wei at al. Oral Dexamethasone vs. Oral Prednisone for Children With Acute Asthma Exacerbations: A Systematic Review and Meta-Analysis. Frontiers in Pediatrics. 2019 Dec 13;7:503. doi: 10.3389/fped.2019.00503.
  7. Craig et al. Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews. Cochrane Database Systematic Reviews. 2020 August 5;8:CD012977. doi: 10.1002/14651858.CD012977.pub2. PMID: 32767571.
  8. Maiya et al. Hypocalcaemia and vitamin D deficiency: an important, but preventable, cause of life-threatening infant heart failure. Heart 94.5 (2008): 581-584.
  9. Freedman et al. Pediatric myocarditis: emergency department clinical findings and diagnostic evaluation. PEDIATRICS 120; 6:1278-85 December 2007 
  10. Panickar et al. Oral prednisolone for preschool children with acute virus-induced wheezing. New England Journal of Medicine. 2009 Jan 22;360(4):329-38. doi: 10.1056/NEJMoa0804897. 
  11. Tessa Davis. Steroids for pre-school wheeze, Don’t Forget the Bubbles, 2018. Available at:
    https://doi.org/10.31440/DFTB.14563
  12. Fernandes RM et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD004878. DOI: 10.1002/14651858.CD004878.pub4).
  13. Wallace et al. Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial. Archives of Disease in Childhood2021;106:339-344.
  14. Tse SM et al. DOORWAY research group of the Pediatric Emergency Research in Canada (PERC) network. Genetic determinants of acute asthma therapy response in children with moderate-to-severe asthma exacerbations. Pediatric Pulmonology. 2019 Apr;54(4):378-385. doi: 10.1002/ppul.24247. Epub 2019 Jan 15.
  15. Morris et al. Which intravenous bronchodilators are being administered to children presenting with acute severe wheeze in the UK and Ireland? Thorax. 70(1):88-91. January 2015.
  16. Dasgupta et al. Myocarditis in the paediatric population: a review. Congenital Heart Disease. 2019;14:868–877.
  17. Kirk et al. The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. The Journal of Heart and Lung Transplantation, Vol 33, No 9, September 2014
  18. Robinson et al. Intravenous immunoglobulin for presumed viral myocarditis in children and adults. Cochrane Database Syst Rev. 2020 Aug 19;8:CD004370. doi: 10.1002/14651858.CD004370.pub4. PMID: 32835416.
  19. Ghelani et al. Demographics, trends and outcomes in pediatric acute myocarditis in the United States 2006 to 2011. Circulation: Cardiovascular Quality and Outcomes. 2012; 5:622-627.

Ten ‘not to be missed’ paediatric ECGs

Cite this article as:
Megan Thomas, Jordan Evans, Amos Wong and Jeff Morgan. Ten ‘not to be missed’ paediatric ECGs, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.29306

To refresh your memory on how to read paediatric ECGs take a look at Anna McCorquodale’s fantastic article: Approaching the paediatric ECG.

Here we review ten ‘not to be missed’ abnormal ECGs that may be encountered in acute paediatrics. 

#1 Supraventricular Tachycardia (SVT)

What is it?

SVT is a narrow complex tachycardia, the electrical activity originates above the ventricles (‘supraventricular’). SVT is classified based on whether it originates from the atrium or from the AV node. Finding where the position of the P wave is (with respect to the QRS complex) during tachycardia (‘P wave hunting’) is essential for the diagnosis of SVT.

Why does it happen?

It usually occurs due to one of the following mechanisms:

  • An accessory pathway linking the ventricle to the atrium, which impulses can travel along returning into the atria (AVRT, Atrioventricular Re-entrant Tachycardia)
  • A micro re-entrant circuit in the AV node itself (AVNRT, AV node re-entrant tachycardia)
  • An enhanced automatic focus in the atrium which fires impulses out 

These all lead to excessive impulses being conducted to the ventricles.

So what do we see on ECG?

  • A fast narrow complex tachycardia (approx. 150-220 bpm)
  • SVT – The hunt for the missing P wave:  It is a common misconception  in SVT that there are no P waves. Whilst this may appear to be the case, this is because the P wave is in fact hidden elsewhere.  The location of the missing P wave will depend on the type of SVT.
  • Lack of beat to beat variability i.e. you will see on the monitor that the rate stays pretty much constant

Atrioventricular Re-entrant Tachycardia (AVRT)

This is when there is an accessory electrical pathway connecting the ventricles and the atria. This creates a re-entrant circuit, with impulses either being conducted down the AV node and then back up the accessory pathway (orthodromic) or vice versa (antidromic).  You may see a retrograde P wave at the end of the QRS complex. (See #2 for further info on Wolff-Parkinson-White Syndrome, a classic type of AVRT).

Atrioventricular Nodal Re-entrant Tachycardia (AVNRT)

A micro re-entrant circuit forms in, or adjacent to, the AV node itself.  Here, P waves are very hard to find as they are usually buried in the QRS complex. The circuit often stimulates both the atria and ventricles and therefore the P-wave is hidden, buried within the QRS complex. 

AVNRT: N for No P waves!

Permanent junctional reciprocating tachycardia (PJRT)

This is a type of orthodromic AVRT where the concealed accessory pathway is near the coronary sinus. This means it can conduct at a relatively slow rate for a tachycardia. The characteristic of PJRT is Long RP tachycardia where the P wave is inverted in the inferior leads (hence NOT in sinus rhythm!) and the RP interval is longer than PR interval.

PJRT is commonly misdiagnosed as sinus tachycardia.  If PJRT is suspected seek cardiology input as adenosine is often ineffective and therefore needing multiple anti-arrhythmic therapy.

#2 Wolff-Parkinson-White Syndrome (WPW)

What is it?

Wolff-Parkinson-White is a conduction abnormality, where there is an accessory pathway connecting the atria and the ventricles. If this accessory pathway conducts from the atria to the ventricles (anterogradely) then it can be seen on the ECG as ‘pre-excitation’, as the impulse will travel faster down the accessory pathway than the rate-limited AV node.  WPW can lead to SVT (AVRT type).

What do we see on ECG?

A short PR interval (<120ms) is seen.

The most distinguishing feature is a delta wave which appears as a slow upslope between the Q wave and the R wave – with the Q wave being much earlier than usual. This means that the QRS is wide (>100ms).  The delta wave reflects fusion between the accessory pathway and the normal QRS as conducted via the AV node.

#3 Complete Heart Block

What is it?

Complete heart block (also known as ‘Third Degree’ heart block) occurs when an impulse isn’t conducted from the atria to the ventricles, usually due to AV node pathology. This means that whilst the atrial rate is determined by the SA node, the ventricular rate is a ventricular escape rhythm –which is much slower than the rate of the SA node. This means that the ventricles and atria, therefore, contract completely independent of one another. In AVN block a narrow QRS is seen, whereas, in an infranodal block, a wide QRS is seen. The former is more stable as the pacemaker site is more proximal (Bundle of His) so asystole is less likely.

Why does it happen?

Heart block can occur for a variety of reasons in children, but often it is congenital- secondary to either structural disease (i.e congenitally corrected transposition of the great arteries) or maternal antibodies, as seen in neonatal lupus. Congenital heart block associated with underlying structural heart disease has a poorer prognosis.

So what do we see on ECG?

There are regular P waves and regular QRS complexes, but these are completely unrelated to one another.

But what about the other blocks?

#4 Myocarditis

What is it?

As suggested in the name, myocarditis is inflammation of the myocardium. This can occur due to infection (viruses, bacteria, spirochetes, fungi, and other organisms) having a direct toxic effect on the myocardium.  It is important to consider the diagnosis in children who have recently suffered a systemic illness (esp. Coxsackie). Certain drugs may also be responsible (anthracycline chemotherapy and alcohol).  Myocarditis may occur alongside pericarditis. The inflamed myocardium is unable to contract and conduct as well as usual resulting in poor function of the heart.

So what do we see on ECG?

Usually, myocarditis presents with sinus tachycardia and non-specific T-wave and ST-segment changes (e.g. T wave inversion). We may also see:

  • QRS/QT prolongation
  • Low voltage QRS (<5mm in precordial leads)
  • Pathological Q waves
  • Ventricular arrhythmias (can be ectopics or VT)
  • AV block 

#5 Dilated Cardiomyopathy (DCM)

What is it?

Dilated Cardiomyopathy (DCM) is characterized by weak and floppy myocardium.  It may be inherited or develop as a result of myocarditis secondary to infection or drugs.

So what do we see on ECG?

Cardiomyopathies show similar features to myocarditis.  Pathologically it’s a spectrum, the inflammation in myocarditis is the ‘active phase’ leading to muscle damage present in cardiomyopathy. Changes may include:

  • QRS/QT prolongation
  • Low voltage QRS (<5mm in precordial leads)
  • T wave / ST segment changes
  • Pathological Q waves
  • Ventricular arrhythmias (can be ectopics or VT)
  • AV block 

#6 Hypertrophic Cardiomyopathy (HOCM)

What is it?

HOCM is a genetic condition that affects the sarcomeres in the heart causing left ventricular hypertrophy (LVH), which cannot be explained by other causes. It is very important as it’s the most common cause of sudden cardiac death in those <35, and those who have HOCM may require an internal cardiac defibrillator.

So how do we figure out if there is HOCM?

There are many criteria that can be used to describe HOCM, however no one criteria has been determined to be the most reliable (especially in children).

So what do we see on ECG?

Whereas in DCM there are small QRS complexes, in HOCM they are large due to the hypertrophied muscle.  As above with myocarditis and dilated cardiomyopathy: T wave inversion and ST changes indicate unhealthy myocardium. Pathological Q waves may also be seen.

#7 Long QT

What is it?

As the name suggests, this is when the QT interval is prolonged. In order to determine if the QT is prolonged then we need to determine the QTc using Bazetts formula.

Source: litfl.com/bazett-formula/
  • In boys, a prolonged QTc is >450ms
  • In girls a prolonged QTc is >460ms.

The most important tool in trying to determine the cause of a prolonged QT interval is history! Certain features make a congenital cause of a prolonged QT interval much more likely:

  • Syncope (+/- stress)
  • Congenital deafness (suggests LQT5)
  • FHx of sudden cardiac death <30 yr in immediate family
  • FHx of Long QT syndrome
  • Certain medications

What causes it?

There are many causes of a prolonged QT interval, including:

Acquired prolonged QT: This is when a child has a prolonged QT interval secondary to an underlying cause such as:

  • Drugs: antibiotics, antidepressants, antipsychotics, antihistamines, antiarrythmics, antifungals
  • Electrolyte disturbances
  • Hypothermia

Congenital long QT syndrome: This is an inherited channelopathy, where the child has a prolonged QT interval present either at baseline or unmasked by a stimulus.

There are 17 different forms of long QT syndrome (and counting!), which each have a different genetic mutation.

Three main types of Long QT syndrome (LQTS):

NameGeneTriggersFrequencyT waves
LQT1KCNQ1Peak exercise40%Early onset broad based.
LQT2KCNH2Sudden loud noises, swimming, emotion, stress30%Low voltage double bumped ‘bifid’ T wave with notching
LQT3SCN5ARest, sleep10%Late onset T wave  

ECG changes may be seen at rest or the child may need to go through exercise tolerance testing or an adrenaline challenge in order to unmask the prolonged QT interval.

So what do we see on ECG?

Nice one, Sherlock, you guessed it!  The main feature is a prolonged QTc interval.      

Why do we care so much about a prolonged QT interval?

Those who have a prolonged QT interval are at a higher risk of developing VT or Torsades de Pointes and therefore sudden cardiac death. This means it is important to identify these children so that they can receive medical therapy or an ICD if deemed necessary.

In paediatric cardiology, Schwartz criteria is used to determine the likelihood of Long QT syndrome. Whilst we do not reach an ultimate diagnosis in the ED, it is useful to note the risky features.

#8 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)


What is it?

As the name suggests, it is a polymorphic (i.e. of multiple morphologies) ventricular tachycardia that is stimulated by catecholamines such as adrenaline. It is an inherited condition, which affects ion channels causing altered calcium flux leading to delayed after-depolarisations causing VT. Whilst baseline ECG may be normal, states in which there is a high adrenaline surge can unmask the CPVT (i.e. heavy exercise). If detected, these children need to be sent for further investigation for medical management or potentially an ICD.

So what do we see on ECG?

A polymorphic ventricular tachycardia. There are two types:

  • Normal baseline ECG!
  • Typical polymorphic / bidirectional VT – where both QRS complexes and T wave change in axis.

Differential for bidirectional VT = CPVT, LQTS Type 7 and Digoxin toxicity.

Do not shock CPVT! This may induce ‘electrical storm’ perpetuate the catecholamine release.  Seek advice from your local Paediatric Cardiologist.

#9 Brugada Syndrome

What is it?

This is an inherited channelopathy which affects impulse conduction, causing ventricular tachyarrhythmias and potentially sudden cardiac death. It is more common in males and commonly seen in carbohydrates consuming nations e.g. rice in South East Asia and pasta in the Western population. Interestingly, the same gene that causes LQT3 (see above) causes Brugada (SCN5A), however in the former there is a gain in function, whereas in Brugada there is a loss of function.

#10 Anomalous Left Coronary Artery arising from the Pulmonary Artery (ALCAPA)

What is it?

This is when the left coronary artery is connected to the pulmonary artery instead of the aorta. This means that instead of receiving oxygenated blood, the left side of the myocardium will receive deoxygenated blood. This can lead to myocardial ischaemia, which is initially transient occurring only in periods of increased myocardial demand (feeding, crying). However, as oxygen demand increases, infarction of the anterolateral left ventricular wall can occur.

So what ECG changes do we see?

  • Pathological Q waves (esp. in leads I, aVL and V6) – 50% of kids with Q waves in aVL have ALCAPA!
  • Ischaemic / T wave changes in inferolateral leads (II, III, aVF, V5-6).  Note on ECG below T waves in V5 and V6 are flattened

Top Tips for Paediatric Cardiology

Cite this article as:
Ana Waddington. Top Tips for Paediatric Cardiology, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28999

Here is our next fabulous little treasure trove of tips on Paediatric Cardiology from Helen Ormrod and Anna Mcquorquodale…

  1. In SVT – use a 3 way tap because the adenosine half life is so small that even if you use a bio-connector, the medication will get lost and you don’t want to be giving more adenosine than you need to.
  2. When performing Pre and Post ductal sats, use the right hand and right leg – as a rule of thumb, looking for a gradient of more than 5 (95% vs 90%). We do this because we are worried about any cardiac lesion that is affecting systemic circulation such as cortication of the aorta
  3. Four limb BP is only useful within the first 3-4 months of life because of the conditions that we are looking for. The gradient has to be 20 or more. Don’t worry if there is a tiny discrepancy.
  4. When following up a patient with a known congenital heart disease, try and find out through their letter or consultant where they are with their surgery. If they now have an anatomically normal heart, we don’t need to be as concerned about their cardiac disease. For example, a PDA ligation 3 years ago.
  5. It’s important to be aware that CHD kids, especially post repair, are more likely to have arrhythmias (even if they have reached a stage where their heart is structurally normal). Arrhythmias that can be quite benign in general kids can have a significantly more detrimental effect on those with CHD (even if repaired).
  6. Fluids are part of a delicate balance. These patients need to remain hydrated in order to help their cardiac function but for the same reason they should not be overloaded. Strict input and output balances are required.
    • If the patient has a cardiac shunt (BT Shunt etc) and are dehydrated, this is a life threatening emergency and can become a cardiac arrest very quickly. Move to resus!
  7. If a child has an uncorrected TOFF and have come in with pyrexia or discomfort need to be managed in HDU bay as they can become sick very quickly. Apply cardiac monitoring and saturation.
  8. If a cardiac baby is septic, there is no reason not to give treatment as they need it to help their cardiac function.

What are some of your top tips? Feel free to share them in the comments below!

For your convenience, the top tips are summarised in an A4 poster format (infographic design by Kat Priddis @kls_kat & Grace Leo @gracie_leo):

Paediatric Murmurs: Ari Horton at DFTB18

Cite this article as:
Team DFTB. Paediatric Murmurs: Ari Horton at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.18861

Ari Horton is many things – an advocate for kindness, a Cordon Bleu trained pastry chef and, just very occasionally, a paediatric cardiologist. Andrew Tagg remembers the day Ari found his calling. Working as a paediatric ED resident in Melbourne’s inner west he came to present a patient. He could barely sit still and his grin threatened to infect the fishbowl as he announced, “I found a murmur!”

We may not all be as acoustically gifted as Ari but that thing we wield around our necks is not just for listening for wheezes or for distracting toddlers.

At 3:30am in emergency overnight,
You got a seriously worrisome fright.
That harsh sound whooshing through the chest,
Try hide your concern, you say “It’s for the best”.
Is it innocent or the beginning of the end,
Go back to the basics they’re your best friend.

Horton’s distraught, his heart is fraught.
Stress fills his tired mind, luckily he left his steth behind.
Numbers and statistics running through his head,
But he stood still watching the child from the end of his bed.
By 9am poor old Horton, more dead than alive,
Had picked, searched and listened to more than 9005

Examination is a dynamic process they say,
Watching the kid run this and that way.
See them feed, sleep, run, jump and cry,
Do some special tests before you say goodbye.
A person’s a person no matter how small

It’s the real story that captures us all.
A murmur’s just a murmur no matter how loud
I’ve learnt my lessons and I’m so proud.
This child is healthy and safe because we cared
Cardiac fellowship awaits because I dared.

Horton Hears A What? Ari Horton (2018)

 

 

 

Here is a little sketchnote by @gracie_leo of the talk:

 

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

DFTB19 has just a handful of main conference tickets left but there are still spots for some of the pre-conference workshops.

 

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

 

iTunes Button

 

Daily JA, Bolin E, Eble BK. Teaching pediatric cardiology with meaning and sense. Congenital heart disease. 2018 Jan;13(1):154-6.
Haney I, Ipp M, Feldman W, McCrindle BW. Accuracy of clinical assessment of heart murmurs by office based (general practice) paediatricians. Archives of disease in childhood. 1999 Nov 1;81(5):409-12.
Keren R, Tereschuk M, Luan X. Evaluation of a novel method for grading heart murmur intensity. Archives of pediatrics & adolescent medicine. 2005 Apr 1;159(4):329-34.
Lefort B, Cheyssac E, Soulé N, Poinsot J, Vaillant MC, Nassimi A, Chantepie A. Auscultation While Standing: A Basic and Reliable Method to Rule Out a Pathologic Heart Murmur in Children. The Annals of Family Medicine. 2017 Nov 1;15(6):523-8.
Mahnke CB, Nowalk A, Hofkosh D, Zuberbuhler JR, Law YM. Comparison of two educational interventions on pediatric resident auscultation skills. Pediatrics. 2004 May 1;113(5):1331-5.
Noponen AL, Lukkarinen S, Angerla A, Sepponen R. Phono-spectrographic analysis of heart murmur in children. BMC pediatrics. 2007 Dec;7(1):23.

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Josh Francis: Paediatrics in East Timor at DFTB17

Cite this article as:
Team DFTB. Josh Francis: Paediatrics in East Timor at DFTB17, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.16238

And so we come to the final talk of the final day of DFTB17 in Brisbane.

You can check out any of our other conference talks on our YouTube channel.

Kawasaki’s Disease

Cite this article as:
Alyssa Courtney. Kawasaki’s Disease, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.12282
A four-year-old Japanese boy was brought into Emergency with 5 days of fevers, non-exudative bilaterally injected sclerae, erythematous pharynx and irritability.

Wondering about the possibility of Kawasaki Disease, I turned to check the 2017 update of the American Heart Association Scientific Statement, focusing on considering a diagnosis of Incomplete Kawasaki Disease.

 

Bottom line:

  • Unchanged diagnostic criteria of complete Kawasaki Disease (KD)
  • Refined algorithm for evaluation of suspected incomplete KD (15-20% of cases)
  • Recommended ECHO at diagnosis, and repeated at 1-2 weeks and 4-6 weeks after treatment
  • Unchanged acute management– Intravenous immunoglobulin (IVIG) single dose 2g/kg over 10-12 hours. Ideally prior to day 10. Some countries continue to use high dose aspirin for varying durations.
  • Additional therapeutic options are outlined for the 10-20% with persistent or recurrent fever
  • New model of KD vasculopathy

 

What is Kawasaki Disease?

An acute, self-limited febrile illness of unknown cause, predominantly in children <5 years. It is the most common cause of acquired heart disease in developed countries. Without pathognomonic tests, we need to detect it clinically!

 

Epidemiology

  • Most common in Japan (where it was first described) with an annual incidence of 264.8 per 100 000 children in 2012. The estimated incidence in North America is 25 cases per 100 000 children <5 years of age per year. Australia has one of the lowest reported rates (3.7 per 100 000 <5 years of age), equivalent to 50–60 cases Australia-wide per year. It is likely that the current Australian incidence is higher.
  • Highest relative risk is in Asian children, especially of Japanese ancestry
  • The ratio of males to females is 1.5:1
  • Predominantly affects children 6 months to 4 years
  • Predisposing factors have been reported inconsistently
  • In Japan, the recurrence rate is 3%, and the relative risk in siblings is ten-fold higher

 

What is the aetiology?

We have no idea why…. BUT the resultant systemic inflammation leads to associated clinical findings: liver (hepatitis), lung (interstitial pneumonitis), gastrointestinal tract (abdominal pain, vomiting, diarrhoea, gallbladder hydrops), meninges (aseptic meningitis, irritability), heart (myocarditis, pericarditis, valvulitis), urinary tract (pyuria), pancreas (pancreatitis), and lymph nodes (lymphadenopathy).

A new model of Kawasaki disease vasculopathy involves three processes impacting muscular arteries. The first is a necrotising arteritis, followed by subacute/chronic vasculitis. The final process is luminal myofibroblastic proliferation.

 

How do we diagnose it in Australia?

Diagnostic Criteria

Fever for 5 days or more (typically high spiking (>39°C to 40°C) and remittent)

Plus 4/5 of:

  • polymorphous rash (usually within 5 days of fever onset)
  • bilateral (non-purulent) conjunctival injection (usually begins shortly after fever onset and often spares the limbus, an avascular zone around the iris)
  • mucous membrane changes e.g. reddened or dry cracked lips, strawberry tongue, diffuse redness of oral or pharyngeal mucosa (oral ulcers and pharyngeal exudates are not consistent with KD)
  • peripheral changes, e.g. erythema of the palms or soles, oedema of the hands or feet, and in convalescence desquamation
  • cervical lymphadenopathy (> 15 mm diameter, usually unilateral, single, non-purulent and painful in the anterior cervical chain)

AND exclusion of diseases with a similar presentation

  • Staphylococcal infection (e.g. scalded skin syndrome, toxic shock syndrome)
  • Streptococcal infection (e.g. scarlet fever, toxic shock-like syndrome not just isolation from throat)
  • Measles
  • Viral exanthems
  • Steven’s Johnson syndrome
  • Drug reactions
  • Juvenile rheumatoid arthritis.

Trickily, these children may have a concurrent viral infection, often adenovirus. Adenovirus is more likely with exudative pharyngitis and conjunctivitis and positive PCR assay. Kawasaki disease is more likely with erythema/swelling of hands and feet, a strawberry tongue, and a desquamating groin rash.

Inflammation and crusting of a recent Bacille-Calmette-Guérin (BCG) injection site may occur.

Consider an alternative diagnosis to Kawasaki Disease if there is exudative conjunctivitis, exudative pharyngitis, ulcerative intraoral lesions, bullous or vesicular rash, generalized adenopathy, or splenomegaly.

 

What is Incomplete Kawasaki Disease?

Scarily, this is so easily missed. They make up 15-20% of all cases!!
Patients with incomplete KD, particularly those <6 months of age and older children, may experience significant delays in diagnosis and these children are at high risk of developing coronary artery abnormalities.

Consider KD if:

  • Infants <6 months old with prolonged fever and irritability
  • Infants with prolonged fever and unexplained aseptic meningitis
  • Infants or children with prolonged fever and unexplained or culture-negative shock
  • Infants or children with prolonged fever and cervical lymphadenitis unresponsive to antibiotic therapy
  • Infants or children with prolonged fever and retropharyngeal oroparapharyngeal phlegmon unresponsive to antibiotic therapy

Evaluation of suspected incomplete Kawasaki disease (via McCrindle BW et al. 2017)

What can we investigate?

As suggested by RCH Melbourne guidelines, all patients should have

  • ASOT / Anti DNAase B
  • Echocardiography (at least twice: at initial presentation and, if negative, again at 6 – 8 weeks).
  • Platelet count (marked thrombocytosis common in the second week of illness)
  • Consider Mycoplasma

In addition, findings can provide support when considering Incomplete Kawasaki Disease – refer to the above algorithm.

Evolution of laboratory findings via Tremoulet et al.

  • KD is unlikely if ESR, CRP, and platelet count are normal after day 7 of illness.
  • Low WBC and lymphocyte predominance suggests an alternative diagnosis
  • Leukocytosis is typical in the acute stage, with granulocyte predominance
  • Normocytic, normochromic anaemia is common during inflammation
  • CRP and ESR elevation is nearly universal, CRP normalizes more quickly with inflammation resolution. ESR is elevated by IVIG therapy.
  • Minimally elevated ESR in the setting of severe clinical disease should prompt investigation for disseminated intravascular coagulation.
  • Thrombocytosis is a characteristic feature that generally doesn’t occur until the second week, peaking in the third week, normalizing by 4 to 6 weeks
  • Thrombocytopenia can be a sign of disseminated intravascular coagulation and is a risk factor for the development of coronary artery abnormalities
  • Mild to moderate elevations in serum transaminases or gammaglutamyl transpeptidase occur in 40% to 60% of patients, and mild hyperbilirubinemia occurs in ≈10%.
  • Hypoalbuminaemia is common and associated with more severe and more prolonged acute disease
  • Urinalysis may show pyuria in up to 80% of children, non-specific for KD
  • In children who undergo lumbar puncture, ≈30% demonstrate pleocytosis with a mononuclear cell predominance, normal glucose levels, and generally normal protein levels

 

Pitfalls

Fever and pyuria in an infant or young child may be diagnosed as a urinary tract infection, with subsequent development of rash, red eyes, and red lips attributed to an antibiotic reaction. Irritability and a culture-negative pleocytosis of the cerebrospinal fluid in an infant with prolonged fever suggestive of aseptic meningitis (or if antibiotics have been given, partially treated meningitis) may cause a diagnosis of KD to be overlooked. Cervical lymphadenitis as the primary clinical manifestation can be misdiagnosed as having bacterial adenitis. Gastrointestinal symptoms are considered for surgical causes, other physical findings of KD can be overlooked.

 

What is the treatment?

We’re aiming to prevent important coronary artery abnormalities. Timely (as soon as possible, ideally within 10 days) IVIG treatment reduces the incidence of coronary artery aneurysms (defined from absolute luminal dimensions) from 25% to 4%. Studies with additional therapies to IVIG have not substantially reduced this residual risk of 4%. Adverse effects are rare but include Coomb’s positive haemolytic anaemia and aseptic meningitis. The measles, mumps, and varicella vaccine should be deferred for 11 months unless at high risk (seek advice, may need repeat vaccination). If the diagnosis is delayed, IVIG should still be given (after the tenth day of illness) IF there is presence of fever, or continued elevation of ESR or CRP>3, indicating ongoing inflammation. Aspirin is used with the theoretical rationale of reducing coronary artery aneurysms (although there is no well-established evidence for this). In Australia, a dose of 3-5mg/kg daily from diagnosis until cardiology review at 6 weeks is routine. The newly released statement advises the administration of moderate to high-dose (80–100 mg/kg/day) aspirin is reasonable until the patient is afebrile. Patients should receive a seasonal influenza vaccination.

Fever usually resolves within 36 hours after IVIG infusion has been completed; if not, the patient is considered to have resistance to IVIG. 10-20% of patients will not respond to the single IVIG treatment dose. There is minimal data to support therapeutic agents for the child with IVIG resistance. Repeating the IVIG dose, 3 days of high-dose pulsed steroids, or 2-3 weeks of tapering prednisolone are all options. There are lower levels of evidence for infliximab and cyclosporine.

 

Coronary artery abnormalities

An angiographic study of 1100 patients showed coronary artery lesions in 24%, with aneurysms in 8% and a number of patients with stenoses and occlusions. Valvular regurgitation is usually mild to moderate in severity and resolves prior to follow-up. MR can occur after the acute stage from myocardial ischaemia. Patients after KD have been shown to have functional and anatomic abnormalities of the aorta with unknown long-term implications. Myocarditis is common during the acute illness but complete resolution is expected. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up.

 

What is the prognosis?

  1. The case fatality rate is <0.1% in Japan, virtually all from cardiac sequelae.
  2. Peak mortality occurs 15 to 45 days after onset of fever, during which time well-established coronary artery vasculitis occurs concomitantly with marked elevation of the platelet count and a hypercoagulable state
  3. Coronary artery aneurysms from KD account for 5% of acute coronary syndromes (ACS) in adults <40 years of age

 

In Summary:

  • Be aware of the diagnostic criteria of complete Kawasaki Disease (KD)
  • Highest relative risk in Asian children, especially Japanese ancestry
  • Always consider incomplete KD (15-20% of cases) and refer to the algorithm if concerns, there are pitfalls!
  • Liaise with cardiology regarding an ECHO
  • Unchanged acute management– Intravenous immunoglobulin (IVIG) single dose 2g/kg over 10-12 hours. Ideally prior to day 10. Some countries continue to use high dose aspirin for varying durations.
  • Additional therapeutic options are outlined for the 10-20% with persistent or recurrent fever, minimal evidence for these
  • New model of KD vasculopathy but we are still in the dark regarding aetiology
  • Coronary artery aneurysms from KD account for approximately 5% of acute coronary syndromes (ACS) in adults <40 years of age

 

 Selected references

McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation2017;Mar 29

Yim D, Curtis N, Cheung M, Burgner D. Update on Kawasaki disease: Epidemiology, aetiology and pathogenesis. Journal of Paediatrics and Child Health 49 (2013) 704–708

Clinical Practice Guidelines, Royal Children’s Hospital, Melbourne

Kim DS, Kawasaki Disease. Yonsei Medical Journal. 47 (2006) (6): 759–72. PMC 2687814 PMID 17191303. doi:10.3349/ymj.2006.47.6.759

Yim D, Curtis N, Cheung M, Burgner D. An update on Kawasaki disease II: Clinical features, diagnosis, treatment and outcomes. Journal of Paediatrics and Child Health 49 (2013) 614–623

Tremoulet AH, Jain S, Chandrasekar D, Sun X, Sato Y, Burns JC. Evolution of laboratory values in patients with Kawasaki disease. Pediatr Infect Dis J. 2011;30:1022–1026

Dengler LD, Capparelli EV, Bastian JF, Bradley DJ, Glode MP, Santa S, Newburger JW, Baker AL, Matsubara T, Burns JC. Cerebrospinal fluid profile in patients with acute Kawasaki disease. Pediatr Infect Dis J. 1998;17:478–481

 

DFTB go to Berlin – #SMACCmini

Cite this article as:
Tagg, A. DFTB go to Berlin – #SMACCmini, Don't Forget the Bubbles, 2017. Available at:
https://dontforgetthebubbles.com/dftb-go-to-berlin-smaccmini/

Having flown 16,893 kilometres to visit family, a short hop over the Berlin was nothing. This year Tessa and I were honoured to be able to help out with SMACCmini – the paediatric workshop before the main event.  DasSMACC is the second-most* anticipated conference of the year and we wanted to make sure the delegates left better able to look after critically unwell children.

Transition from Fetal Physiology

Cite this article as:
Andrew Tagg. Transition from Fetal Physiology, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.10360

The imminent arrival of another Tagglet (not to be confused with aglet*) has prompted me to go back to my textbooks and refresh my knowledge of what to expect.  One of the problems of being a medical parent is being expected to know the answers to the most random of medical questions that are thrown out there. Is it supposed to look like that? Why are her hands that colour? And the question that is really being asked is, “Are they normal?” So here begins a series of posts on what is “normal” in neonates.

PAC Conference – Pflaumer on Sudden Death in the young

Cite this article as:
Goldstein, H. PAC Conference – Pflaumer on Sudden Death in the young, Don't Forget the Bubbles, 2016. Available at:
https://dontforgetthebubbles.com/pac-conference-pflaumer-on-sudden-death-in-the-young/

We have teamed up with APLS to share the videos from their Paediatric Acute Care Conferences. These videos have never been open access before, so if you weren’t able to attend the conferences, then now’s your chance to catch up.

The PAC Conference is run each year by APLS and consists of presentations on a range of topics relevant to paediatric acute and critical care.