Tuesday, 26 February 2019

Too much choice - What milk do you need to give a baby with a feeding problem?

To paraphrase one of my favourite comedians (John Finnemore) - Once upon a time there was too little choice.  Then around 1980, there was just the right amount of choice.  Now, there is way too much choice.  In paediatrics, this is perhaps more true for special milks than any other treatment decision we make.

Have you been to a supermarket recently to buy some milk?  Just trying to find what you want when you know what you want can be overwhelming.  Should it be 0% fat?  1%? 2%? Organic? Cow's milk? Goat's milk? Filtered? I could go on but you get the idea.  There is just too much choice.

The same is true when trying to decide which milk to use* for a baby with a feeding problem.  There are so many possibilities that it can be quite confusing.  Don't worry though - all the choice is an illusion.  There are only a few real differences which can easily be explained.  The best way is probably by going through the problems rather than the milks.  So here we go.

*Note that this only applies to choice of formula in formula fed infants.  While breastfed babies less commonly develop problems such as milk allergy, the solution is not to change them to a formula feed.  It should be possible to continue breatfeeding no matter what the problem is.


What is it?  Nobody knows. No cause has been found to really explain why some children cry a lot of the first few months of life.

Which special milk helps this condition?  There is no good medical evidence from RCTs published in peer reviewed journals that I know of to support the use of any special milk.  The keystones of managing colic are to rule out other pathology and to give a good explanation of the condition to the parents.  Ultimately, the only thing that really works to resolve colic is the passage of time.

Gastro-oesophageal reflux disease (GORD)

What is it?  It is normal for babies to reflux/ regurgitate milk.  GORD is the term used to label reflux associated with significant symptoms such as marked and persistent distress.  The amount of milk that the infant brings back is not what separates GORD from physiological reflux.  If a baby has several large regurgitations a day but is minimally affected, this is not considered to be a disease. (1)

The first thing to do is to make sure that the infant is not overfeeding.  This is a surprisingly common scenario that is reasonably simple to manage.
If you suspect that the distress and vomiting is related to overfeeding, try reducing feeds to 150ml/kg/day under the age of three months and to 120ml/kg/day if over the age of three months.  Those targets are a rough guide and overfeeding is only likely to be the issue if the volume of feed is well over those guideline amounts.

Which special milk helps GORD? Most infants with GORD are symptomatic due to reflux of milk, rather than having a problem with acid reflux.  This is almost certainly why the evidence for routine use of acid suppression treatment (PPIs and H2 blockers) suggests little or no effect.

For infant GORD without red flags the mainstay of treatment is to avoid over-feeding, and to use a thickener in a standard feed.  Alginate preparations should be used as second line treatment since they have a high risk of causing constipation.  There are reflux milks on the market which are essentially standard milks with thickener already blended in.  These are not usually prescribed.

Lactose Intolerance

What is it?  Inadequate production of the enzyme lactase in the bowel means that lactose (the sugar in milk) is left undigested.  Bacteria then ferment this sugar and produce noxious chemicals which inflame the bowel, further diminishing the ability to produce lactase.

Lactose intolerance is often secondary to an episode of viral gastroenteritis, in which case it will resolve (and more quickly so with the right milk).  Primary lactose intolerance is actually very rare according to the epidemiologists.  There is an inexplicably large difference between the epidemiology of lactose intolerance, and the frequency with which it is diagnosed by parents and clinicians.

Possible reasons for the overdiagnosis of lactose intolerance include:
  • Lack of specific symptoms - normal infant crying and colic might be labelled as lactose intolerance
  • Confusion with Cow's Milk Protein Allergy, which is more common.
  • Confirmation bias - Colic and reflux symptoms both have a tendency to resolve in time.  If the resolution of symptoms happens to occur after a change in milk, this will give the wrong impression that the special milk caused the improvement in symptoms.
Which special milk helps this condition?  If an infant genuinely has lactose intolerance then a lactose free milk will result in a dramatic resolution of symptoms, usually within days.  There are numerous lactose free formulas which are commercially available.  Soy milk is also lactose free but is not recommended for infant boys as the effect of phytoestrogens is unknown.

Lactose free milk does have the potential to cause more dental caries than standard milk, so there is good reason to avoid the overdiagnosis of lactose intolerance.

Cow's Milk Protein Allergy (CMPA)

What is it?  Well, confusingly, there are two types of CMPA.  IgE type CMPA is what you might call a classic allergy.  With this immediate type of response to cow's milk protein, typical symptoms include wheeze, urticaria, swelling etc.  Usually, it is quite obvious that the child is having an allergic reaction, leaving the main question to be what the allergen was.

In most cases, infants usually have a non-IgE CMPA.  This is sometimes referred to as milk intolerance, which causes it to get confused with lactose intolerance.  I prefer to avoid that term to avoid this misunderstanding.  Non-IgE CMPA is predominantly an enteritis, without systemic features.  As such the symptoms are vague and difficult to distinguish from other conditions such as GORD and colic.

Clues that an infant may have non-IgE CMPA include
  • Onset of symptoms at an age which is atypical for GORD (e.g. over 6 months old)
  • Symptoms that may originally have suggested GORD but fail to respond to treatment or progress despite treatment
  • Lower GI symptoms
  • Significant eczema.  The relationship between eczema and CMPA is complicated.  Eczema is quite common and colic is also common.  As a result, it would be foolish to say that eczema + unsettled child = CMPA.  However, there are many infants whose eczema and unsettled behaviour seemed to resolve as soon as they were treated as CMPA.
Which special milk helps this condition?  The best way to stop an an allergic reaction is to remove the allergen.  In order to reduce the allergenicity of the formula, CMPA milks have the proteins broken down to varying degrees.  While there are partially hydrolysed feeds available, an extensively hydrolysed feed (EHF) is recommended for a child with CMPA.  There are many EHFs available.

One pitfall in the prescribing of milks to children with CMPA is to confuse lactose free milk with EHF.  Another is to accidentally prescribe an amino acid formula, because these are also licenced for use in CMPA.  Amino acid formulas are only used for extreme cases of CMPA.  These feeds are quite unpleasant and rather expensive, so EHFs should be first line unless there is a specific reason to chose an amino acid feed.
Amino acid feeds (AAFs) are generally reserved for use in secondary care.  This type of milk is the ultimate in hypoallergenicity (real word?) but is also very expensive and rather unpleasant to taste.  AAFs are usually resorted to rather than being chosen first line.  Indications include severe IgE type allergy or non-IgE allergy that does not respond to an ECF.

One alternative to use first line is soy milk.  This may or may not be successful as a treatment strategy.  The problem with soy milk is that although it does not contain cow's milk protein, it is not in itself hypoallergenic.  Many infants who have reacted to cow's milk also react to soy milk so you end up no further forward when that happens.  There is some caution regarding the phyto-oestrogens that are found in soy milk.  Although it is an unproven risk, the concern is that these chemicals may have an effect on infants and so it is sometimes recommended that soy milk is not given to boys under the age of six months old.

Parents may also want to try other mammalian milks (e.g goat).  Most dietitians recommend that these are avoided due to the poor nutritional content.  Again, these milks are not hypoallergenic and there is significant risk of further reaction.

The most important part of managing non-IgE CMPA is that the diagnosis is a three part process.  First the diagnosis is suspected.  Then, is the infants symptoms settle with treatment the diagnosis is provisional.  Only when the infant is re-established on a standard formula and the symptoms return is the diagnosis confirmed.
When introducing an ECF, it is worth considering that the infant may object to the taste of the new milk.  Although nowhere near as unpalatable as an AAF, ECFs do have a distinctive taste difference from standard feeds.  A sudden switch can cause problems at feeding times.  One strategy to avoid this is to blend the new milk in over a few days.  If the infant is on a 6oz feed, use 5oz of standard feed mixed with 1oz of ECF on the first day.  On the second day, increase that to 2oz of ECF and 4oz of standard feed.  After a few days, the infant should be fully established on the new ECF feed.

The best way to avoid the problem of too much choice is to simplify things.  Find out a locally available ECF or check your local guideline/ formulary.  That way you only need to know one milk- choice doesn't get more simple than that.

Edward Snelson

Disclaimer - I frequently buy the wrong milk.
Gastro-oesophageal reflux disease in children and young people: diagnosis and management
NICE guideline [NG1] January 2015

Edward is fundraising for the development of the Sheffield Children's Hospital Emergency Department.  If you found this post useful and would like to support that cause, this link will take you to the donations page.  GPpaedsTips is free to all and produced without expectation of any such donation, but if you don't ask...

Wednesday, 13 February 2019

Should you give ibuprofen to a child on an empty stomach?

In the previous post, I gave some general principles about prescribing for children.  One person took the time to get in touch about the issue of ibuprofen on an empty stomach.  This is an interesting controversy and is an issue well worth understanding.

Ibuprofen is a useful medication when it comes to symptom control in the unwell child.  Studies on the benefits of ibuprofen when co-administered with paracetamol (acetaminofen) have tended to show that there is no additional benefit when it comes to controlling fever.  However, pyrexia is no longer generally thought to be the enemy and there is no clear indication to normalise an unwell child's temperature.  That doesn't mean that the child will not benefit from analgesia.  One of the issues with children who have upper respiratory tract infection (URTI) is that they are often reluctant to drink, either due to a general feeling of being unwell or due to the pain associated with trying to drink.  If paracetamol and ibuprofen have a clear role in managing the unwell child it is this: making the child feel comfortable and well is an important part of giving them the best possible chance to have good oral intake.  If fever is not the enemy then dehydration certainly is.  If an unwell child is refusing fluids and a combination of paracetamol and ibuprofen resolves that, why wouldn't you?

One of the anxieties that this situation causes is the fear that these are the very children at risk of the complications of ibuprofen.  Ibuprofen, being a non-steroidal anti-inflammatory drug (NSAID) is associated with renal impairment and gastrointestinal (GI) bleeding.  Should it then be avoided in children with poor oral intake?

First, let's look at the renal issue.  The short answer is that while renal impairment is a risk in dehydrated children (1), it is safe in children who are not dehydrated (2), even if at risk of dehydration.  If ibuprofen can potentially aid oral hydration, it seems safe to use, providing the child is not already showing signs of dehydration.  It is also worth noting that in the study reporting acute kidney injury (AKI) in children taking ibuprofen, all made a full recovery.

Second, the issue of GI bleeding.  Although case reports of children having GI bleeds during short term use of ibuprofen exist (3), these are associated with incorrect administration.  Significant GI complications of ibuprofen are associated with long term use, concomitant steroid use, known GI ulceration or coagulation defects (4).  Short term, correct use of ibuprofen in children without risk factors seems to be safe.

The way that ibuprofen risks GI complications is a systemic effect.  It reduces prostaglandin production, thereby reducing the natural protection of the gastric mucosa.  Although we are often told that ibuprofen should be taken with food to reduce GI side effects, there is a debate about whether this should be the case at all.

Advising that analgesia should be given with or after food delays the effect (5) of the pain-killers without clear benefit in terms of gastric protection.  It is unclear as to whether taking ibuprofen with food reduces side effects such as nausea but it shouldn't have an effect on the risk of GI bleeding. As one publication puts it: "Apart from providing unsubstantiated ‘safety’ information by advocating food intake with NSAIDs it may be more appropriate to advocate OTC NSAIDs be taken on a fasting stomach in order to achieve a rapid onset of action and hence avoid an ‘extra’ dose of the drug because the rapidity of pain relief did not meet the patient's expectations." (6)

The bottom line is that as long as a sensible clinical assessment has taken place, ibuprofen can be given to a child who has not eaten.  It may even be best practice.

Edward Snelson
Unintentionally inflammatory

Many thanks to Gina Johnson for her comment on the previous post.  Keep them coming! 
  1. Balestracci A. et al, Ibuprofen-associated acute kidney injury in dehydrated children with acute gastroenteritis, Pediatr Nephrol. 2015 Oct;30(10):1873-8. doi: 10.1007/s00467-015-3105-7. 
  2. Lesko SM, Mitchell AA, Renal function after short-term ibuprofen use in infants and children, Pediatrics. 1997 Dec;100(6):954-7
  3. M─ârginean, M et al, Ibuprofen, a Potential Cause of Acute Hemorrhagic Gastritis in Children - A Case Report, J Crit Care Med (Targu Mures). 2018 Oct; 4(4): 143–146
  4. Berezin et al, Gastrointestinal Bleeding in Children Following Ingestion of Low-dose Ibuprofen, Journal of Pediatric Gastroenterology and Nutrition: April 2007 - Volume 44 - Issue 4 - p 506–508, doi: 10.1097/MPG.0b013e31802d4add
  5. Moore R. et al, Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs – a systematic review, Br J Clin Pharmacol. 2015 Sep; 80(3): 381–388.
  6. Rainsford K, Bjarnason I, NSAIDs: take with food or after fasting?, J Pharm Pharmacol. 2012 Apr;64(4):465-9.

Sunday, 27 January 2019

Prescribing for children - Top tips

Prescribing for children can be tricky. Getting the right medication, dose and formulation should make all the difference to the effectiveness of the treatment plan. Getting one of those wrong is all too easy.

What are the things that we need to know and tips for getting it right?  Here is a detailed list.  There's a shorter and more condensed list below this.
  • Only use medication that has a clear indication.
  • Prescribe a licensed medicine for a licensed indication where possible.
  • Any reasons for prescribing an unlicensed medicine should be clearly and accurately documented.
  • Don't give medication for the sake of doing something.
  • Use a children's specific formulary.
  • Children are less likely to recognise and associate side effects with their medication. This lack of insight by the child is another reason for being judicious about prescribing.
  • Know the weight of the child. Even if doses are age banded, if the child is very large for their age you might choose to go up a little before their birthday.
  • If there is a choice between age banded doses and weight defined doses, go by weight unless overweight for height.
  • Most weight based doses have an upper limit (e.g. nebulised adrenaline), and this can be reached at an early age so always check what the maximum dose should be.
  • When calculating a weight-based dose, check that it looks like a reasonable number.  Calculation errors with a factor of 10 are made all too easily. Don't just copy off the calculator onto the prescription.  Ask if it seems like a dose that makes sense compared with an adult dose.
  • Use a syringe to give the medicine.  It is often better tolerated than a spoon, and the dose can be more accurately measured.  The correct dose can be marked onto the syringe.
  • Use a formulation that the child will tolerate.
  • If a child is sick less than 30 minutes from when medicine is administered, it is OK to repeat the dose as a one-off.
  • Consider alternative routes.  Children with neurodisabilities often have problems with oral medication but may tolerate suppositories.
  • If newly prescribed medicines are to be administered by PEG/NG/NJ tube discuss with a pharmacist to determine the safest formulation and any special administration requirements (e.g. the need to avoid a formulation that will interact with components of the tubing or the need to dilute the dose to avoid blocking the tube).
  • There is almost always a non-pharmacological aspect to any treatment.  Make sure that this is completed either first or as well as the pharmacological treatment.  For example, a hot, miserable child in four layers of clothes doesn't just need antipyretics.  They also need to take all or most of their clothes off.
  • Don't assume that a rash or other symptom is a drug allergy.  (Full post link here)
  • Don't scale down inhaled salbutamol to the size of the child.  Children may need more sprays. Telling a parent to give one spray to a two year old will not be effective.  (There is science behind this - click here for a link to the full explanation.)
  • Don't assume that medication that has been prescribed is the correct dose.  Children grow out of their dose and may no longer be receiving a therapeutic dose. Check the weight of the child and make sure that their long term medication is in the therapeutic range.

Let's consider a few scenarios.

Child 1

A 20-month-old boy sees you with a cough, runny nose and a fever for two days. The child hasn't eaten all day. The parent is giving regular paracetamol, but the temperature is still a concern to them. Examination shows a red bulging left ear drum.

What about antibiotics?

The natural course of otitis media is to begin resolving after about the third day of symptoms. A significant number of children experience side effects such as vomiting or diarrhoea from antibiotics such as amoxicillin. On balance, an antibiotic is unlikely to cause benefit, and the risk of side effects is similar in size so at day two of symptoms it is probably better to maximise symptom relief.

How do we improve symptom relief?

1 - Optimise the dose of paracetamol
It is often assumed that a child being given paracetamol is receiving a therapeutic dose, but this is not always the case. Often the child is being given too little for some possible reasons:

Human factors-
The parent is using a bottle that was prescribed some time ago.  The dose was correct at the time but is no longer adequate. The parent will assume the dose is correct because the bottle has the child's name on it.
The parent has given the medication in the expectation of a cure. After a few doses of paracetamol, when the symptoms return, they assume that the medication is not effective and stop using it.
The parent is using both paracetamol and ibuprofen and has assumed that to use both, the dose of each needs to be halved. As a result, the child is having sub-therapeutic doses of each medication.
The parent is simply being cautious for fear of overdosing the child.

Pharmacological factors-
The dose is based on age banding. Age banded doses for drugs with a narrow therapeutic index (such as paracetamol) have to err on the side of caution.  The weight of a 20-month-old child can vary hugely.  Paracetamol is ineffective below 10mg/kg, and the BNFc recommends a dose of 15-20mg/kg 4 hourly, up to four times a day for post-operative pain. Otitis media is painful. It's time to weigh the child.

The child weighs 14 kg. What dose should of paracetamol should they have?

If the parent is giving 120mg/dose as per age banded doses in the UK, the child is receiving 8.5mg/kg which is subtherapeutic. The weight of a 20-month-old boy can vary from 9 kg (9th centile) to 13 kg (91st centile) according to the WHO growth charts.  Paracetamol is fat soluble and so overweight children should not have a full mg/kg dose.  It is generally agreed that paracetamol should be given to children based on their ideal body weight.  How to achieve that is debatable, and guidelines vary.

Option A - The scientific way: Check the child's weight. If it is over the 91st centile, check their height.  Look at the growth chart to wee what height centile they are. Then check the growth chart for the corresponding weight on the centiles. For this child, if height was 88cm, that sits on the 91st centile. The corresponding ideal weight would be 13 kg.Use that to calculate a 15mg/kg paracetamol dose. In this case 200mg/dose.

Option B - Use clinical judgement. Does the child look to be an appropriate weight for their height? If so the prescribing based on the child's actual weight is reasonable. Does the child look overweight for their height? If so, prescribing on actual weight may result in overdosing. Use age banded doses or option A to be safe.

Supposing the dose of paracetamol is already therapeutic and being given regularly, what do we do then? What should the parent do if optimising the paracetamol dose doesn't work?

2 - Adding in ibuprofen

Sometimes, paracetamol on its own is not enough to control symptoms. Otitis media is often one of those times. This clinical scenario presents a common dilemma. We are told that ibuprofen should be given after food to minimise the risk of gastritis. On the other hand, the child who is in pain and feeling unwell is unlikely to eat and sometimes will refuse to drink.

It is common practice to give ibuprofen in this scenario for short periods (a few days). In children, gastric bleeding is usually associated with prolonged NSAID use. In this situation, ibuprofen is likely to improve oral intake. The practice of giving ibuprofen to children refusing to eat or drink is based on a balance of risks. The risk of GI side effects from the NSAIDs is felt to be outweighed by the risks of not analgesing, which would mean inadequate oral intake.  For a fuller explanation of when and how to give Ibuprofen to a fasting child, read this post.

What about a cough medicine?

There is no good evidence for or against the use of over the counter cough medicines in children. Codeine-based medicines are not an option, and the rest are unproven regarding efficacy. In the absence of good evidence of benefit, it is usually best to avoid medication in children who are unwell. It can be hard enough for the parents to manage to give the medication that is likely to relieve symptoms without adding one that is unlikely to do so.

Child 2 

An 18-month-old girl-year-old presents with wheeze and some increased work of breathing. She started with a runny nose three days ago. She looks happy and well. She is well hydrated. There is a mild subcostal recession and a wheeze that is heard throughout the chest. The parent says that this happened the previous month and they were given a salbutamol inhaler which they were told to give one puff of four times a day.

How do we treat the wheeze acutely?

In this age, the likelihood is that this is a viral wheeze - bronchospasm triggered by a viral infection. Bronchiolitis, which mainly affects the under one-year-olds, does not respond to beta-agonists while viral wheeze does. Salbutamol will only work if it is given in effective amounts. So, the best thing to do here is to confirm the diagnosis and optimise the treatment by giving 6-10 spays of salbutamol from a metered dose inhaler (MDI) via an age-appropriate spacer.

1 - Get the dose right.

Although for most paediatric treatments, doses are an appropriate fraction of an adult dose, salbutamol is an exception. The reasons are multiple and involve a bit of science. I've written a full explanation of why children need bigger doses of salbutamol when wheezy here. Most guidelines recommend 6-10 puffs repeated at 15-20 minute intervals to gain improvement and 4-6 puffs every four hours to maintain that reduced bronchospasm.

2 - Get the formulation right

It is tempting to use a nebuliser to treat infants and small children. They tend not to comply with spacers unless they are used to them, so a nebuliser feels like an easier option. There are several problems with that practice, however. One issue is that it sends a message to the parents that the inhaler is not the ideal treatment and so may make them ambivalent about using an MDI and spacer, preferring instead to come for a healthcare professional to give them the magic mask. Another problem is that people learn by watching and through demonstration. A parent watching an expert use the devices will help them to do it optimally at home. Better still, if someone talks through some top tips while it is given, they will benefit from the experience. Nebulised salbutamol is best used when oxygen is needed concurrently.

3 - Get the technique right

Learning good inhaler technique is a process of explanation, demonstration and practice.  It should never be assumed that inhalers are being given in an ideal manner unless we have checked.  I start my 6-10 puffs by getting the adult to do the first two sprays, followed by me doing the second two and then getting the adult to do the rest, demonstrating any suggestions I have made to do it differently.

4 - Confirming the treatment is appropriate

If the correct drug has been given in the correct amount in the best way, the child will respond. If the child has a clear improvement we have proven the diagnosis and that our treatment is effective. If there is no clear response or the child gets worse, we need to rethink. The two main possibilities are a wrong diagnosis or inadequate treatment. As a rule, with a wheezy child who has increased work of breathing despite initial treatment, we need to escalate our treatment (which may involve calling for help) and consider other diagnoses at the same time.

What about oral steroids?

This is a good case to demonstrate how important it is to keep up to date with the evidence (or to regularly read some FOAMed that does that for you!)  In the past it was fairly normal to give oral steroids to any wheezy child.  There is now good evidence to show that steroids have no role in treating bronchiolitis.  The evidence also suggests that steroids have no significant effect in wheezy children under the age of five.  Unless a child under the age of five has a diagnosis of possible asthma (made by a paediatrician), steroids are generally avoided.

What about antibiotics?

The child has signs of an infection and has a breathing problem, so the temptation is to give antibiotics to cover possible pneumonia.  There are several reasons not to do this. Firstly, a lower respiratory tract infection (LRTI) is very unlikely because the child has a wheeze. There is good evidence that wheezing is a strong negative predictor of LRTI. (1) This also makes sense clinically. Pneumonia causes systemic unwellness and significantly increased work of breathing. If a child has a consolidation in some of their lung and bronchospasm in the rest, you won't be thinking, "maybe I should prescribe oral antibiotics.." you'll be thinking, "let's get this child admitted." (Link to post on this subject here)

Child 3 

A parent brings a six year old child with a barking cough and noisy breathing. When you get to see them, they have visible breathing difficulties and loud stridor. They have a significant recession and look pale/ slightly blue.

What is the priority?

1 - Non-pharmacological management.

This child almost certainly has severe croup. Whatever the cause of the stridor, they have a critical airway. The first thing to do is remain calm. The flow of air through the narrow airway could be suddenly compromised by forcing a change in position of by upsetting the child. This is a perfect time to bring in the non-pharmacological first rule. You need to reassure the parent and keep the child comfortable and able to find their own position to maintain their airway.  Now call for help and get out some epinephrine and oxygen.

2 - Pharmacological management

If the child tolerates it, give 15 litres/minute of oxygen via a mask with a reservoir. Grab the epinephrine (adrenaline) vial (this might be from the anaphylaxis kit in a community setting). The BNFc gives a dose of 400 micrograms/kg. How much does the child weigh? You might have a recent weight but if not, the formula [(age plus 4) times 2] is pretty accurate up to the age of six and gives a rough weight which is all we need in an emergency. So 0.4mg x 20 kg gives us an epinephrine dose of 8mg. However, the maximum dose is 5 mg.  So that is 5mls of 1/1000 epinephrine. In the nebuliser, it goes and onto the face of the child. This will buy some time while help arrives. If there are a really good response and the child will tolerate it, give 150 micrograms/kg of dexamethasone orally.

So in summary: Don't panic, do give oxygen, estimate weight, calculate the dose of nebulised epinephrine, realise that dose exceeds maximum dose, give a maximum dose and remain calm while doing all of that.
While prescribing for children is different, all of the usual principles apply.  There are a few things that are particular to paediatric prescribing, and I hope this has helped by giving some general advice and specific examples.

Edward Snelson

Disclaimer:  If this post is rubbish it's not my fault.  I brought in subcontractors from Scotland's Pharmacy in Practice team in the form of  Stephen-Andrew Whyte and Johnathan Laird.  If you think the post is brilliant then I suppose I must give some credit.  (Seriously though, thanks for your input both of you.  It was much appreciated.  Thanks also to all the people who shared their top tips with me.)

  1. Hirsch, A et al, Estimating Risk of Pneumonia in a Prospective Emergency Department Cohort, The Journal of Pediatrics , Volume 204 , 172 - 176.e1
  2. British National Formulary for Children
  3. Medicines for Children online resource

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.