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.