Tuesday, 8 January 2019

Opiates in children - we need to talk about codeine

Things have changed a lot with regards to opiods and children and young people over the past few years.  In 2013, the UK Medicines and Healthcare products Regulatory Agency (MRHA) recommended that codeine should no longer be used under the age of 12 years old (1).

To kick off 2019, The American Academy of Paediatrics has published an article regarding the opiod epidemic in young people (2).  These two things actually had nothing to do with each other.  The MHRA advice was about side effects and not about addiction.

What are we supposed to use instead of codeine?  Well, the seemingly contradictory answer that you may or may not have heard is (wait for it...) that we should instead use morphine to provide moderate pain relief to children.  That's not as crazy at it first sounds but it does require some explanation.  The explanation begins with a bit of pharmacology.  Then by adding a bit of physiology it all starts to make sense.

First the pharmacology:  Codeine is not itself the thing that produces the opiate effect.  Codeine is metabolised to various things, the most important of which is morphine.  Essentially, when you prescribe codeine, you are prescribing morphine via the metabolism of the liver.

Secondly the physiology.  The codeine-morphine metabolism that occurs in the liver varies in speed and completeness from person to person.  It is estimated that about 2% of the population are fast metabolisers.

The end result is that when someone takes codeine, there is a variable conversion to morphine.  The morphine which results and has a clinical effect is produced in amounts and over a time frame that varies from person to person.  While slightly less information exists about Dihydrocodeine, it is similar enough to codeine to make all of the above applicable.
Is this possibility of harm all just speculation?  There is some weak evidence that codeine may be to blame for some child deaths, mainly in use as an analgesia following tonsillectomy. (3)  It was these cases which prompted the ban on the use of codeine under the age of 12 in the UK.  Although there are plenty of reasons why the deaths reported here are not generalisable to all children requiring strong analgesia, a recurring theme is that children who died often had the fast metabolism gene.
Despite concerns and rulings, codeine is still used frequently in children. (4)  Now it seems that young people are choosing it themselves more and more. (2)

The good news is that opiates are rarely needed in children outside of a hospital setting.  If strong analgesia is required on a temporary basis, oral morphine is often prescribed where codeine would have once been given.  This paradoxical move has come about through better understanding of how opiods work and the effect they can have in children and certain patient groups.

We need to be wary of opiates and opiods in children.  These drugs definitely have an important place and we shouldn't hesitate to use them appropriately when acute analgesia is needed.  A good first choice option for oral strong analgesia is oral morphine, while for a more rapid onset, intranasal diamorphine works very well.

It seems that in the past we were lulled into thinking that codeine in particular was a soft and safe option.  The evidence of recent years has told us that in terms of prescription use and abuse, this is not the safe drug that it was thought to be.

Edward Snelson
  1. April 2015 Monthly Newsletter,  Medicines and Healthcare products Regulatory Agency
  2. Sharon Levy, Youth and the Opioid Epidemic, Pediatrics Jan 2019, e20182752; DOI: 10.1542/peds.2018-2752
  3. Kelly, Lauren et al, More Codeine Fatalities After Tonsillectomy in North American Children, Pediatrics May 2012, 129 (5) e1343-e1347; DOI: 10.1542/peds.2011-2538
  4. Chua KP, Shrime MG, Conti RM. Effect of FDA investigation on opioid prescribing to children after tonsillectomy/adenoidectomy. Pediatrics. 2017;140(6):e20171765.

Wednesday, 12 December 2018

Making the Right Judgement - a comprehensive 3D model for deciding what to do with each child with a respiratory presentation

In the previous post, I covered how best to make a diagnosis of lower respiratory tract infection (LRTI).  Anyone who has the pleasure of working with acutely ill children knows, the diagnosis is only a small part of what we do.  A big part of what we do is making that all important decision - home or hospital?

This decision is usually made up of several elements.  What is interesting is that the same principles can be applied to all of the major respiratory problems that we see, namely:
  • Bronchiolitis
  • Viral Wheeze
  • Asthma
  • Croup
  • Pneumonia (LRTI)
Once one of these diagnoses has been made, the decision about whether to admit or manage at home is a huge one.  On the one hand, we don't want to admit children to hospital unnecessarily.  Apart from the inconvenience and stress to the family, there is a significant risk of adding insult to injury as so many children who attend hospital acquire additional infection.  On the other hand, we know that if a respiratory problem does deteriorate, it can do so quickly and catastrophically.  If there is a significant risk of a child going off, they should be somewhere that can respond appropriately.

In the majority of childhood respiratory illnesses, the treatment itself is not what requires the child to be in hospital.  It is no longer routine to have a chest X-ray and intravenous antibiotics for uncomplicated community acquired pneumonia. (1)  Many children who are admitted with pneumonia receive no investigations and are treated with oral amoxicillin and discharged when they show improvement.  Severe croup is often a waiting game.  Viral wheeze is usually treated with inhalers via spacer.  Babies with bronchiolitis are often observed while a team of expert paediatricians avoid the temptation to "try something" that research has proven to be pointless.  You get the picture.  These are the times that paediatrics is the art of masterful inactivity.  Believe me, that is harder than it sounds and is actually quite labour intensive when done properly.  The point is, they still need to be there, because these are the children who, if they got worse, would require escalation of treatment.

So if the need for hospital specific treatment isn't always the thing that determines the need for admission, what else is?  In illnesses that always need hospital treatment (e.g. Kawasaki Disease) the decision is made for you.  However in respiratory problems that can be treated in the community, the decision is mostly about risk assessment, which is never as simple as people make it sound.

Guidelines often imply that the assessment of a respiratory presentation is a simple matter of deciding severity or calculating a score.  I like an over-simplification as much as the next clinician, except when it doesn't work, which is fairly often.  Why isn't it that simple?  Because not a one dimensional assessment.  The good news is, it's not that complicated,  It's just 3D instead.

D1 - Severity

The first dimension of the assessment is to decide severity.  All acute respiratory problems, like chain coffees, come in small medium and large.  Deciding which presentation fits into mild moderate or severe is fairly intuitive and the same principles apply across the different diseases.
Severe makes the decision easy.  Severe needs to be treated in hospital for several reasons.  Severe is usually a set piece, and although severe can be terrifying, it's not usually a cause of decision fatigue.  That comes from deciding what to do with the rest of them.

In a previous post, I shared some thoughts on croup scores and severity.  You can read that via this link if it would be helpful.

Mild cases of croup, bronchiolitis, viral wheeze, asthma and LRTI are almost always best managed at home.  Almost.  Moderate cases can often go either way.

D2 - Risk factors

This means that other factors are involved in the decision.  Because we are assessing risk, we need to consider risk factors.  These, when applied to the severity of the illness literally multiply the risk of something bad happening.
As a rule, a risk factor alongside a moderate severity of respiratory problem is ore than enough to mandate admission to hospital.   That child with croup that you were thinking of sending home- I suspect that decision will be changed when you factor in the fact that they were born prematurely at 26 weeks.

What is slightly more complicated is how risk factors apply to the child with a mild presentation.  It's complicated because the presence of a risk factor does still ramp up the risk, but its a factor applied to a very small risk in the first place.  What's more, the same risk factors that apply to the presentation also apply to the risk of being in hospital.  An ex-premature baby with mild bronchiolitis could go off, but the risk is still small.  An ex-prem baby in hospital if they don't need to be is a risk all of its own.

The decision about what to do with a child who has a mild respiratory problem but also has risk factors is a difficult one.  It is a decision best made by an experienced clinician who understands the way that the particular risk factor interacts with the illness and knows the pitfalls associated with it.  If you're not sure, refer or discuss the case.  This may be a good opportunity for an experienced primary care clinician to share that decision with an experienced paediatician via a telephone consultation.

D3 - Red Flags

Finally, there are red flags.  Although independent of the apparent severity of the presentation, these features will usually mandate referral or admission.

A good example of a red flag feature would be a 4 month whose clinical examination is consistent with mild bronchiolitis.  If the accompanying adult says that the infant had an episode of suddenly becoming pale and floppy earlier that day, this should be treated as a warning sign.
Bringing those three dimensions together will give you the answer to the "home or hospital?" question.  It will also help the communication between primary and secondary care.  Referring a child with a respiratory problem, summarised as diagnosis, severity, risk factors and red flags is just showing off.  There's nothing wrong with that is there?

Edward Snelson
Dimensional Relativist

Disclaimer: I'm never sure which is worse: oversimplification or undersimplification.

  1. Guidelines for the management of community acquired pneumonia in children: update 2011 British Thoracic Society Community Acquired Pneumonia in Children Guideline Group

Friday, 30 November 2018

Making a Diagnosis of Lower Respiratory Tract Infection in Children

This is one of the most common and difficult calls in General Practice, Emergency Medicine and acute Paediatrics: when to treat a child as a lower respiratory tract infection.  It's important because we don't want to miss a diagnosis of LRTI/ pneumonia, yet overtreating is bad medicine.  It's difficult because most children with an upper respiratory tract infection will have a cough and fever, and because the parents will be worried about the possibility of LRTI.  To make things worse, any child with uncomplicated URTI could later develop LRTI.  Not often, but often enough that it can influence our decision making.  So how do we get it right?

I think that it is a question of rule in/ rule out.  There are many elements to the assessment but there is one feature that determines whether the default is to assume that there is no LRTI and whether the default is to assume that there is a LRTI.  That feature is respiratory abnormality.
I think that when I was taught as a medical student, the auscultation findings in the chest were over-emphasised.  The reality is that these can be misleading.

First of all, the presence of focal findings in the chest are common even in the absence of LRTI.

  • The infant or child with URTI will often have crepitations that can be hear in one or more places in the chest.  These may be transmitted sounds or due to secretions.  Breath sounds will be normal throughout.  In the absence of abnormal breathing, these crackles are not good evidence for LRTI.  Often, these noises go away or move around if re-examined, especially after a cough.
  • The infant or child with a wheeze may have crepitations and variation in the loudness of breath sounds in different parts of their chest.  Bacterial LRTI does not usually cause wheeze but wheezy problems often lead to focal findings.  The clue that the problem is not a LRTI is that the child is systemically well.  The basic rule is this: if a child with a wheeze does not look ill enough to be admitted to hospital, they do not have a bacterial LRTI.  Bronchiolitis and viral induced wheeze are all the explanation needed for abnormal breathing.  If a child had one of these and a pneumonia, they would really be in difficulty. 
  • The child with viral induced wheeze may have no wheeze to further complicate things.  Consider a trial of beta-agonist inhalers in well child with respiratory distress, especially if there is a past history of wheeze. 
Secondly, the absence of focal findings in the chest is a relatively common scenario in the child with LRTI.
  • Auscultation and percussion in infants and small children is difficult.  Chests are small and there is always the possibility that the area of abnormality will be missed.  The child with cough, fever and abnormal breathing should be presumed to have a LRTI unless proved otherwise.
  • Not all LRTIs even produce focal signs.  Sometimes a segment of a lobe is all that is infected (known radiologically as a round pneumonia) and it is quite common in such cases for the only clues to be the combination of unwellness and respiratory abnormality.

Nor should we rely on chest X-ray (CXR) to make the decision for us.  The sensitivity and specificity of CXR as a way to diagnose pneumonia in children is too poor to justify using radiation when the diagnosis should be made clinically.   The BTS guidelines for community acquired pneumonia in children and the Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America both recommend that CXR and blood tests are routinely avoided. (1,2)

There are no absolute rules.  This is paediatrics so there are special circumstances.

  • Small infants and babies should be considered to have a higher probability of serious bacterial infection whenever they present.  However that should not mean a liberal use of oral antibiotics in a community setting.  If you are treating them differently because they have that higher risk of serious infections, they are also high risk for other reasons and should usually be referred if LRTI is suspected.
  • Children with complex medical problems may not demonstrate abnormal breathing or unwellness in the way that normal children do.
  • Children with chronic LRTI may be less unwell and have little in the way of respiratory abnormality.  Parents will often seem less anxious if the problem is developing more gradually.  Daily cough for several weeks should be taken seriously.  It is not unreasonable to try a course of broad spectrum oral antibiotics but be aware that this may not be the end of the problem.  Underlying causes including foreign objects, bronciectasis and simply unresolved LRTI may need to be ruled out in which case referral will be necessary.

Bringing all of these things together shows that there are two key features.  The first of these is abnormal breathing in the context of an unwell child with cough.  The presence of abnormal breathing almost immediately makes it overwhemingly likely that the problem is LRTI, bronchiolitis or viral wheeze.  The second feature is wheeze, which largely rules out LRTI.  It's almost that simple.  Almost...
For more on how to tell the difference between bronchiolitis and viral induced wheeze, read this post: "Why Do Different Children Wheeze Differently? - Simple, but first you have to understand all of paediatrics"

It is important to remember that LRTI is usually preceded by URTI.  Safety-netting advice is key.  Here's an example of the kind of thing that I tell parents: (3)
Ruling in and ruling out is a dynamic process.  Involving the parents is an important part of that.

Edward Snelson
Not a member of the ruling class

Disclaimer: Knowing whether you approach the problem from primarily a rule in or rule out approach is a bit like knowing whether you are coming or going, neither of which I am usually sure of.

  1. Guidelines for the management of community acquired pneumonia in children: update 2011 British Thoracic Society Community Acquired Pneumonia in Children Guideline Group
  2. Bradley J et al, The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America, Clinical Infectious Diseases, Volume 53, Issue 7, 1 October 2011, Pages e25–e76, https://doi.org/10.1093/cid/cir531
  3. The Essential Clinical Handbook of Common Paediatric Cases, Edward Snelson

Monday, 5 November 2018

How do we diagnose sepsis in children? The Sepsis Jigsaw

Sepsis in children is something that we all fear.  It is difficult to define and  difficult to diagnose early.  This millennium has seen a huge rise in the presence of sepsis in education, campaigns and guidelines.  I believe that one of the reasons that we're talking about it so much is that we're still trying to understand what we mean.  Within that, we are trying to find ways to explain some of the things that we know.  That is because a lot of what we know about recognising sepsis is tied up in tacit knowledge.

Tacit knowledge refers to the things that we know but are not easily explained.  For example, it is  difficult to explain all the elements involved in driving a car.  Much of what we do in our lives relies on tacit knowledge.  How do you find things?  How do you figure things out?  These are far easier to do than to explain.

The very nature of the recognition of sepsis makes it something that needs completely taking apart and putting back together.

Sepsis is not easily definable in the first place.  2016 saw the Third International Consensus Definitions for Sepsis and Septic Shock (1).  This came from a process that involved two previous attempts to find consensus definitions, a recognition that none of the previous definitions were perfect, and a third brave attempt to find a definition for something that is somewhat amorphous.

The resulting definition:  "life-threatening organ dysfunction caused by a dysregulated host response to infection" is a good one and I would agree with it.  However, it does little to help us diagnose sepsis in children.  Recognising severe sepsis is not a great challenge.  Recognising early sepsis in children is very difficult because of the way that children respond to illness.
There is a bit of a misunderstanding that could result from many of the recent guidelines and publications about recognising sepsis in children: that fever plus tachycardia equals sepsis.  Since febrile children are routinely tachycardic, this does not make sense.  The misunderstanding comes from a retrospective approach to guideline definitions of sepsis.  If you look at all the children who were diagnosed as septic, what were the common features at presentation?  Abnormal temperature (high or low) and tachycardia come up a lot.

There are two sides to this coin.  Sepsis in children is not simple.  It is difficult to recognise and thwarted by many biases.  Yet it is deadly and anything that we can do to improve our recognition of sepsis is going to save lives. So complexity is no reason for complacency.
Since we don’t have a retrospectoscope when we see our next patient, we need to have a good way of recognising possible sepsis and serious bacterial infection (SBI) amongst the large numbers of children with uncomplicated illnesses.  If fever and tachycardia are not specific, what can we rely on?  Despite hopes to the contrary, routine near patient testing (e.g. CRP) in a primary care or emergency department setting will not give us the answer.

If neither numbers nor tests can sort the few out from the many, what is left?  Simply put, a global assessment made by an experienced clinician is what really brings the magic to the decision making.  So what is it that helps them to make a decision?  The answer is complicated but essentially, they put together a jigsaw of features and come up with enough of a picture so that the puzzle makes sense.  Some of the jigsaw pieces are fairly obvious but some of them are less well known or involve that tacit element of the process.  It is worth being aware of the various factors that influence this crucial decision.

The pieces of a sepsis jigsaw puzzle:

Abnormally low or high, infection will affect temperature in some way.  This is an oversimplification which fails to address some of the subtleties of temperature and its relationship to bacterial infection and sepsis.

Factors to consider are:
  • Low temperature in the context of an unwell child is more indicative of sepsis
  • The relationship between height of temperature and sepsis/SBI is loose.  Although there is a correlation between very high temperatures and SBI, it is a weak one.  Children with viral infections may well get temperatures over 40˚C.
  • Temperatures that are more persistent or fail to come down with antipyretics are often seen as more concerning.  Again, this is a poor discriminator as this can be seen in viral illnesses.  However, it is also true that a child with a persistent temperature may not get the opportunity to demonstrate their wellness by having a little run around.
  • A normal temperature at the time of assessment does not rule out sepsis.
Circulation: Heart rate, central capillary refill and peripheral perfusion
The normality of these factors is quite rightly reassuring.  If outside of a reference range, these features may or may not be significant.  Each of these factors can be affected by pain, fear, pyrexia and environment.  Again, the extremeness of the abnormality is a consideration as is the persistence of deranged markers of circulation.

Respiration: Respiratory rate and work of breathing
Abnormal respiration is more discriminatory for SBI and sepsis, assuming that there is no other reason for being unwell and breathing abnormally (e.g. viral wheeze).  The reason for this is that respiration is less prone to the physiological changes that affect circulation.  Abnormal breathing may be caused by acidosis or hypoxia but is less likely to be due to a simple illness.  This ties in nicely with the definition of sepsis that relates to organ dysfunction.  While circulation changes may be a reaction to an uncomplicated viral illness, respiratory changes are more likely to be due to organ dysfunction.

Significant episodes
Since we might only see the child for a few minutes, it is important to take seriously any significant events that have occurred recently.  Pale, floppy or blue episodes are all notable.  Shivering and shaking are also worth taking into account.  They are not in themselves proof of serious infection.  Any of these things can occur during a temperature spike in an uncomplicated viral illness.  Remember that each of these is only a piece of a jigsaw.  You need to look at the whole picture and if the child is now running around pretending to be Spiderman, they’re probably OK despite the thing that happened.

Fluid balance
A well hydrated child (wet mucosa etc) who is drinking well and has good urine output is what you are looking for here.  Where these things are not adequate, sometimes all that is required is analgesia and a fresh start.  It all depends on how the rest of the pieces of the jigsaw are coming together as to whether it is time to go down a particular path.  Dehydration and poor urine output combined with other features is more significant.

Activity, behaviour and interaction
Now we are truly into the area of tacit knowledge.  (I wondered when he was getting around to that...)   Very little is published about the relationship between a child’s ability to smile, play, run or do anything for that matter and their risk of having SBI or sepsis.  However, it is reasonably intuitive that a child who runs in, smiles and talks the hind leg off of you is less likely to have sepsis than a child who is carried in, interacts little and looks miserable.   These factors rarely feature meaningfully because they are impossible to quantify.  Each appraisal is as different as each child is unique.  I couldn’t tell you what my threshold for ‘active’ or ‘interactive’ is because it will be specific to the child and depends on factors that I could not explain easily.  That is tacit knowledge in a nutshell.  While no-one can tell you what you are looking for in this category, it is an important piece of the jigsaw and should be give the weight it deserves.  Your instinct here is vital.
If you use these things in your decision making then that is completely normal.  An article in Archives of Disease in Childhood this year (2) published a consensus of which behaviours are seen to indicate that a child does not have sepsis.

Parental anxiety
More tacit knowledge here folks.  We will ask about symptoms and are looking to get some fairly specific answers.  Much of what we want to know will feed into the features already mentioned.  However, there may be things going on that a parent will struggle to articulate.  It is our job to distinguish between unwarranted anxiety (“I saw that news story about the child who died of sepsis…”) and the anxiety that comes from  a parent knowing that something is deeply wrong and being unable to articulate the reason why they know that.  The latter is the parent’s own tacit knowledge being given to you in the form of a person who cannot be reassured.

The trajectory of the illness
I believe that this may be one of the most important yet least discussed pieces of the jigsaw.  No one has told me about it and it may be that no one has ever told you, but when I say it, your own tacit knowledge about assessing unwell children will hopefully agree with the following statement:  An illness that has extreme fluctuation in symptoms (i.e. very unwell followed by surprisingly well) is almost certainly an uncomplicated viral illness.  I am talking about the “you wouldn’t believe how unwell they looked” kind of illness.  Sepsis and SBI don’t give you time off.  Viral illnesses, it seems, do.  So much so that a child who was floppy and lethargic can within the hour be smiling, playing drinking and complaining that they don’t want to go home because they want to play with the toys that you have.  It’s not in the guidelines but it is very important because the opposite is also true.  Two children can have the same heart rate, temperature, hydration and appearance, but the one who hasn’t had a return to normal in the past few hours is the one to really worry about in my opinion.
Many of these jigsaw pieces are the more quantifiable and traditional features that guidelines rely heavily on.  The rest are more woolly and difficult to define, let alone describe.  These are the pieces of the jigsaw that only you, the experienced clinician, can piece together.  If you would like to do a bit more reading about decision making in paediatrics, here is an article published in ADC (open access) (3) which further explores that issue.

Interestingly, there is a paediatric decision tool that takes into account some of the tacit knowledge features described here.  The POPS (Paediatric Observation Priority Score) includes features such as gut feel alongside physiological values (4).  This scoring system is both simple and over-simple in equal measure.  While it is quick, easy to do and validated, it only gives you a number at the end, not an answer or a diagnosis.  That number tells you to look at the jigsaw and see what the numbers mean.  The higher the number, the harder and longer you need to look and the better the explanation you need in order to be happy.

The other thing about POPS is that it doesn’t include my much neglected feature: the trajectory of the illness.  I think I’ll make a modified version of POPS which includes this.  I’ll call it POPcycleS.

How do we disgnose sepsis in children?  It remains a clinical diagnosis, best made by someone who has all the pieces of the sepsis jigsaw.

Edward Snelson
Perpetually puzzled physician

Disclaimer - If there is a piece of the jigsaw missing, go back and reassess the child.  They have probably eaten it.

Tuesday, 23 October 2018

The Practicalities of Croup Management in the Community

This post is in response to a very specific question from a local GP. The question wasn't about recognising croup or even about the best evidence based treatment.  Recognising croup is fairly straightforward. There is pretty much consensus on the best management of croup. The question was about the practicalities.

The evidence for the ideal management of croup has given us a fairly straightforward and reasonably robust answer: a single 0.15mg/kg dose of oral dexamethasone.  Sounds simple doesn't it?  The difficulty is that a single dose is actually quite problematic from a pharmacy point of view. As a result the decision isn't always about the best available evidence.  It might also be about the best available medication and formulation.  To determine the answer to this question, we need to go back a couple of steps.

Croup is a clinical presentation involving barking cough, with or without stridor and respiratory distress.  This usually occurs in a relatively well child, though they will have the symptoms of a viral upper respiratory tract infection.  Like so many presentations in childhood, the underlying cause is a viral illness but the problem is due to the effect or response to the virus.  In the case of croup, that effect is upper airway inflammation and swelling.

When should croup be treated?
Croup is usually classified into mild, moderate or severe.  This can be done with or without a croup score.  While it is a minor oversimplification of what happens next, the likelihood is that severe croup will be treated with steroids and often admitted to hospital while moderate croup will usually be treated with steroids and discharged home after a period of observation.

It is the management of mild croup which often generates the most discussion.  The first question is whether it should be treated at all.  There is evidence that treating mild croup with corticosteroids (1) reduces symptoms.  There is the suggestion that it is safer to treat mild croup in that there is a reduction in time spent in hospital and reduced readmission rate for those that are treated.  However there is no specific evidence that not treating mild croup leads to an increased risk of severe or life threatening croup.  This leads some clinicians to the conclusion that if a child has a barking cough but no stridor or respiratory distress, they prefer to provide safety-netting advice and reassess if the child develops new signs.

How should croup be treated?
There is also evidence regarding the most effective steroid treatment for croup in children.  Oral dexamethasone outperforms oral prednisolone.  Both oral treatments outperform nebulised budesonide.  The suspicion is that dexamethasone outperforms prednisolone because it is better tolerated.  It's difficult for a medication to be effective if it's just been puked onto the floor.

If that's all so well evidence based, what's the problem?  Lets's get on with giving them all dexamethasone 0.15mg/kg. The problem with this is that is that dexamethasone liquid has done itself out of a job.

Dexamethasone is given as a single dose in the vast majority of cases.  The evidence shows that this works well, quickly (2) and with an effect which is sustained over several days.  It is quite potent, so small doses are effective.  These factors, combined with an unpredictable demand and a relatively short shelf life make dexamethasone liquid something that doesn't make business sense for pharmacies to stock.

I recently asked the twitter community about what they had available and while many did have dexamethasone liquid, it certainly wasn't routinely available.  The question also sparked a smattering of stories from people who had been sent from place to place looking for one that had some dexamethasone available.

This then presents a dilemma for the clinician in the community.  Do you prescribe the best tolerated and most effective treatment and take the risk that it will be unavailable?  Do you prescribe an alternative (soluble prednisolone) that is known to be slightly less effective and less well tolerated on the grounds that a medication can only be effective if it's actually been given?

There is also an opportunity to be proactive about the issue.  You could get a member of your team to contact the local pharmacies and ask if any of them do stock liquid dexamethasone.  If not, perhaps one would in which case they would be where you sent your children with croup for their treatment.

On a larger scale, primary care groups (e.g. Clinical commissioning groups in the UK) could coordinate something so that each locality has a pharmacy that stocks liquid dexamethasone.

Another way of looking at it is that there is a vicious cycle to break.  Because dexamethasone is not always available, not everyone provides it.  Because it is not prescribed often enough, it is not always stocked by pharmacists.  More prescribing of dexamethasone should make it more likely that dexamethasone will be stocked.

It is possible that liquid dexamethasone will become a more commonly prescribed medication since it has recently been suggested that it is as effective as prednisolone for childhood wheeze. (3)

What about age banding and using soluble dexamethasone?

Dexamethasone has a large therapeutic window.  The current recommended dose of 0.15mg/kg is a quarter of the dose of 0.6mg/kg which was previously the most often used dose.

This is good because age banding doses is very difficult.  A four year old can be anything from 13-22kg based on the 9th-91st centiles of the WHO growth charts.  Knowing the age is therefore nowhere near as good as having an actual weight.  Obtaining a child's weight does not require any special equipment.  If a child will not stand on a set of scales, simply weigh an adult carrying the child and without holding the child.  The difference is the child's weight.

If using Using the 9th-91st weight centiles and aiming for a dose of 0.15-0.3mg/kg gives the following results:

The ideal is definitely to have a weight and to have a liquid suspension available that would allow the precise dose of 0.15mg/kg to be given.  However, when thinking about a plan B, it seems a shame to go to Prednisolone which is known to be less effective, has more side effects and can only be given in aliquots of 5mg.  Why not do the same with dexamethasone, even if it does mean that the dose may be over in some cases?  Again, the therapeutic window of dexamethasone allows this to be possible.

Although liquid dexamethasone is not always on the shelves of the local pharmacy, it probably should be and possibly would be if it was more often used and the pharmacist knew that the bottle would get used.

Edward Snelson
Pharmacoeconomist of the year 2020

Disclaimer - If treatments are better but do not make sense financially, children should have to pay for that themselves.  If necessary, there are some coal mines near me that could be reopened, giving the children an opportunity to earn the money to pay for all the wasted dexamethasone that they are responsible for.


Wednesday, 3 October 2018

Don’t say, "Eat healthily." Say. "Eat differently."

It’s highly likely that at some point you have had a conversation with a parent or child about the dietary changes that a child needs to make if they have constipation.  This discussion is fraught with difficulties.  Hands up if you’ve ever heard any of the following:
  • My child eats healthily.
  • Are you saying that I don’t give my child healthy food?
  • I can’t make him eat anything?
  • My child is just a fussy eater.
Sometimes it feels like we are pushing water uphill when we’re trying to explain the importance of diet and fluid intake.  The NICE guidelines for management of childhood constipation (1) de-emphasised the dietary part of resolving the problem.  That is not because diet is unimportant.  It is because dietary changes alone are not seen to be adequate and it is necessary to return normality through the use of macrogol laxatives.  When I ask people why they think constipation is so common in children, they often say that it is because children eat badly.  That may be a factor but the main reason that children become constipated is because they are children.  They have poor visceral awareness, no understanding of what their stools and bowel habit should be, and their behavioural response to the problem worsens the situation.  “It hurts when I poo.  I know, I’ll stop pooing!”

Although macrogol laxatives may be an essential part of the solution, dietary change is still important since management of idiopathic childhood constipation is a game of two halves.

So, why is it so difficult to address the lifestyle changes that are so key to success?  There are several reasons.

The first issue is to do with what is normal.  Parents and children alike only have themselves and those close to them as a reference for what is normal.  It’s hardly an ideal sample, especially when by definition at least one of the people in the reference set has constipation.  Similarly, they will look around themselves when asking themselves what is a normal diet.  As a comparison, ask yourself “What is the normal number of cars for a family of five to have?”  If you look at the globally statistical answer, the answer is zero cars.  Most of us would think about the families in our street or social sphere, not considering the bigger picture.

That’s fine though, because we’re not asking people to feed their child normally, we’re asking them to give their child a healthy diet.  That’s right isn’t it?  It’s technically true, but I think that practically and socially, it is the wrong message.

This is because the second difficulty is that the diet discussion is liable to provoke negative feelings.  As soon as you talk about healthy eating, people become defensive.  They may not vocalise it but that is how they are likely to feel.  There are really only two possibilities.  The first possibility is that they believe that the diet offered to the child is already healthy enough.  The message that the child's diet is not healthy is likely to be perceived as critical, which in turn will sabotage the impact of the message.  The second possibility is that they already know that they are giving an unhealthy diet to the child.  Talking about healthy eating is probably going to ignite feeling of guilt and inadequacy, also getting in the way of the ability to move forward.

Getting the language that we use in this important part of the consultation has the potential to radically alter patient and parent buy-in to what you are recommending.  I would suggest that you try changing just one word.  Instead of talking about eating healthily, talk about eating differently.  I usually explain that no matter what a child’s diet is like, there are always changes that can be made that will help them stay free of constipation.  Let’s think about what changes you could make, since constipation is such a horrible problem that every change that has an effect is great progress.

Here are some things that you could look at with the next constipated child you see:

Achievable changes
  • Cutting out sugary drinks
  • Reducing sweet snacks and starchy snacks (chips and crisps)
Easy wins
  • Change breakfast cereal to something high fibre
  • Ask school to allow a water bottle at all times and a permissive approach to toilet access
Practical tips
  • Don't use sweet and starchy snacks as a reward or treat, even for eating healthy food
  • Don't have the constipation food in the house at all. Instead have fruit out and permanently available
  • Give parents permission to not feed the child. If the child has been offered a healthy meal and they refuse it, don't offer them an alternative. Take the food away and let them know that they can have it back if they change their mind.
  • Tell the family that everyone finds it hard to make changes.  Because constipation is a long term problem, every small change can have a big effect.
Prescribing the laxative is the easy part. Making changes that will have a long term effect is much harder.  It's important that the family understands that we know how challenging it is.  It's also important that they know that we are not asking them to change from unhealthy to healthy.  Diet is not binary. What we do need is positive change.  It's time for the child to eat differently.

Edward Snelson
Definitely different

Disclaimer: I have to admit that my kids never got a second crack at their food because I always ate it if they wouldn't.  I'm sure that's fine.  It is fine isn't it?

  1. Constipation in children and young people: diagnosis and management, [CG99]. NICE, 2017

Thursday, 30 August 2018

You Better Think! - A three dimensional guideline for recognising the unusual diagnosis in the ill child (including Kawasaki disease)

When assessing ill children, it is easy to presume that the problem is an uncomplicated viral infection.  Most of the time it is.  The odds are severely stacked against a more significant diagnosis to the extent that it is easy to become overly presumptive.  This, combined with the fact that a simple and benign illness will share many features with a rare or dangerous illness means that spotting the unusual or harmful diagnosis is very challenging indeed.

Much of the work done on congitive and diagnostic error takes the errors and then works backwards.  For a long time there have been reports on the number of deaths in healthcare that are related to error. (1)  These are reverse-engineered and start from the point of the problem.  People died - what is the evidence that there was any flaws in the care/ diagnosis/ treatment?  This is very different from the alternative approach of:  People had a healthcare episode- what happened next?

Outcome based stats are dangerous in that respect.  If you have 10% more adverse events than your colleagues but see 50% more patients (because you're awesome at your job) then please come and work with me.  You might flag up as a dangerous clinician if someone looks purely at incidents rather than the big picture.

I think that the most effective clinicians are those capable of recognising well children and capable of changing gear when something is unusual.  This is sometimes referred to as type 1 and type 2 thinking as per the model descibed by Croskerry. (2)

Using this model, we are most efficient when we are thinking inuitively and making gut feel decisions (type 1 thinking) and most effective at making the more complex diagnoses and managing the most dangerous scenarios when we are more considered and thorough (type 2 thinking).

Let's use this example to consider a child with non specific symptoms such as fever, rash, lymphademopathy and pharyngitis.  The reasonable but also dangerous assumption is that the child has an uncomplicated viral illness.  The possibility of another outcome is small but the consequences of missing an alternative diagnosis are great.  So, we need to use type 1 thinking to be efficient and be prepared to go into type 2 thinking when needed.

The obvious questions are then, what am I looking for and when do I look for it?  Guidelines on the subjects of febrile children, URTI in children and recognising complications such as sepsis tend to be written as if the problem was one dimensional or that the same guideline could be used in every circumstance.  This is one of the reasons that guidelines can sometimes frustrate.  Clinicians don't think that way, so it jars when a "fits all sizes" guideline over-simplifies such a complex process.

Here's an example of something that is useful but fairly simplistic.

This tells us what normal and abnormal look like.  It does very little to tellus what it all means.  Stopping here would be fine if we are just going to tell people when to refer or not.  To do that safely, such guidance will invitably err on the side of caution.

What it fails to do is to address what may be causing the red flags or atypical findings.  While a diagnosis is not necessesary in order to make a decision to refer, having a suspected diagnosis helps us to get the right child to the right place at the right time.

Lets take two of the possible complex and dangerous diagnoses as examples.  A child has a febrile illness with conjunctivitis, phayngitis, swollen lymph nodes, a rash and is pretty miserable.  Good to know.  If I told you that the onset of symptoms was within the past 24hrs, would you consider Kawasaki disease? No.  If I told you that it was day 6 of the illness and that for the past 3 days the child was neither better nor worse would you think that the diagnosis was likely to be acute sepsis? No, but can we get a guideline to help us get there?

Since it is a factor in our decision making, we could add in the dimension of time and disease progression to our guideline.  If we did that I think that it could look something like this:

Even adding this dimension doesn't fulfil our need for something which maps to our way of thinking.  We now have the bit that focuses on the child in front of us and the bit that takes into account the real world where patients present in different ways, but many guidelines fail to take into account the fact that different diseases behave differently.  Worse than that, the differences can be subtle.

Guidelines often struggle to deal with the fact that medicine is a complicated subject.  Do you write a guideline for a clinical scenario (e.g. febrile child)?  If so, you need to include every possible cause and when to think of it.  Do you write your guideline about a specific disease (e.g. Kawasaki disease)?  If so, how will people know when to use the guideline?  If they have looked it up, they are 90% of the way there and the guideline is going to be more useful as confirmation and treament advice.

For these reasons, guidelines will never be a substitute for the need for clinical knowledge and understanding.  Our child with non-specific symptoms guideline needs to have another layer - specific diagnoses, what they look like and when to consider them.

We need guidelines to be both simple in order to be practical and complex because nothing is simple.  We need them to be based on real-world clinical practice and to be honest about the uncertainties inherrent to that.

The short answer to the child with non-specific symptoms?  Anything is possible, including Kawasaki disease.  Early recognition of Kawasaki disease is important as treatment will reduce complications.  So, you better think.  In fact, because type 1 thinking will do very nicely most of the time, but not all of the time, you better think think.

Edward Snelson
Occasional overthinker

Disclaimer: Over and under-thinking are both perfectly acceptable in the right circumstances.

  1. Kohn LT, Corrigan JM, Donaldson MS. To err is human: building a safer health system.National Academies Press, 1999.
  2. Croskerry P. A universal model of diagnostic reasoning, Acad Med. 2009 Aug