This post follows my notes from Day 1 of the Virtual Colloquium – 14th Annual Update in Paediatric Emergencies. Day 2 was another mixed bag of talks, from paediatric analgesia and sedation, to the philosophy of ARDS (yes, really) and then toxicology. Read on for more thoughts and recollections.
Greta Palmer – Paediatric Pain Management in ED
Paeds pain management is an interest area of mine; in fact, I was honoured to get the chance to talk about it at EuSEM in Torino back in 2015.
A/Prof Greta Palmer is an anaesthetist from Melbourne who took us through her thoughts on paediatric pain management. It’s important to note that her talk focused on pharmacological pain management, which is definitely important and one of the first things that comes to mind when we talk about pain. I’d like to maintain, however, my personal viewpoint – that pain is more than just nociception (so pain management should be more than just drugs).
Understandably, the talk began with the simple analgesia we use daily in PED.
Paracetamol administration by the PR route is not common practice in Australia; however IV formulation is becoming more available. In terms of regular administration, most centres are capping at 60mg/kg/day in QID/QDS or 6hr dosing, which achieves an effective plasma concentration of 10mg/L including in neonates. Loading doses of paracetamol are still acceptable, although this practice has decreased. 20mg/kg PO should have an effect for 6h but other than that there’s probably no need to further space doses.
One of the more common questions we are asking in the ED is how to dose paracetamol for obese patients, including children. Dosing for most medications is based on lean body weight – but this study from NZ suggests that dosing by lean body weight for paracetamol in obese patients we are effectively underdosing. If we want to use paracetamol as an opioid-sparing agent, we need to dose paracetamol by total body mass – and crucially this might result in some doses we would be otherwise quite uncomfortable with… one to think about.
For chronic use, 15mg/kg/day x 4 per day is safe acutely – and we don’t yet know chronologically when this becomes a problem. We have seen adult patients using higher doses in combination with other agents (in Australia the example is panadeine forte) without liver injury. In cachectic patients, we need to assume glutathione depletion and as such it makes sense to reduce to 7.5mg/kg/day x 4 dosing for malnourished paediatric patients.
Paracetamol in pregnancy had previously been associated with asthma in children; newer research has found the asthma association is lost when adjusted for upper respiratory tract infection in the child, and the association between paracetamol in pregnancy and ADHD in the child is lost when paracetamol is used short term (<8d) but stronger for chronic use (>28d); though, of course, correlation does not imply causation.Studies have given us a greater appreciation of cardiovascular effects of paracetamol – patent ductus arteriosus closure is seen as effectively with paracetamol as with ibuprofen and indomethacin in this Cochrane review.
Hypotension has been reported with both available IV formulations of paracetamol, and while this was originally attributed to mannitol this is not the mechanism as it happens with the non-mannitol containing formulation. This is particularly relevant for critically unwell patients in ED or ICU – 5% of patients have a >15% drop and 10% have a 10-14% drop in blood pressure.
In the Paeds ED, we hear lots of worries from parents about giving ibuprofen to their child with asthma – or worries about possible allergy. My thought process is that the ED is probably the safest place to have an allergic reaction… but it might be reassuring to know that hypersensitivity to NSAIDs is uncommon, there’s likely some subclass specific reaction eg the “profen”s vs the “fenac”s. There is some cross-sensitivity between groups but it’s probably worth arranging testing to see what is appropriate for patients long term, rather than excluding all NSAIDs.
In children with mild episodic asthma, non-selective NSAIDs infrequently precipitate bronchospasm and data suggest that the anti-inflammatory effect actually reduces exacerbation frequency in episodic URTI-induced asthma. The subgroup of asthmatics who are at risk of NSAID-exacerbated respiratory disease (ERD) are those with severe asthma and upper airway inflammatory disease eg polyps, moderate/severe allergic rhinosinusitis – and in this group the COXibs are safe and don’t cause NSAID-ERD.
That said, all NSAIDs and coxibs can cause renal impairment, although it is usually reversible. AKI can be precipitated if the patient is hypovolaemic or hypoperfused so we might want to think carefully before giving ibuprofen to the febrile, unwell child who is also a bit dry.
You might also have been aware of history concerns around fracture non-union or malunion with NSAIDs – now we have a systematic review and a meta-analysis which have found that NSAIDs use in the context of limb fracture does not result in non-union. For us in the ED, if there is inflammation associated with the fracture and the limb is immobilised in a cast, there is no problem giving ibuprofen in short term. As yet, there’s no strong evidence around maximal duration of therapy.
Discharge prescribing of opioids to adult patients has increased in the last 15-25y in USA and Australia, though data from the USA suggests that numbers are stable when it comes to paediatric patients. Codeine was still in use in 2015 in USA for children, despite contraindications, and oxycodone use has been increasing. Similar trends have been reported in Australia in 2017 but there is no increase seen in data from NZ. The percentage of children using opioids long term post discharge is similar to adults – 4.6% of previously opioid naïve adolescents were using opioids 90-180d post operatively. This is higher following multi trauma although data regarding pain indications was not provided (eg juvenile rheumatoid arthritis).
Prescription opioids were the commonest cause of poisoning death in children 2003-2013 in Australia in this study accounting for 24.4% of cases. The majority of those children were teenagers and the overdoses were unintentional, occurring in the home. Overdose is usually due to pure agonist opioids in children, rather than the more complex medications adults use.
Incidence is bimodal, occurring with age <6y accidentally (remember to check for topical patches in obtunded kids) and in teenagers, when overdose is usually unintentional from experimentation rather than an intentional suicide attempt.
Buprenorphine patches have been previously thought to have a respiratory ceiling but in overdose we’ve seen the full spectrum of opioid depressant effects. Fortunately the resistance to naloxone that is seen in adult buprenorphine use is not seen in children.
Tramadol remains problematic; even at therapeutic doses it can cause agitation and seizures, with seizures and hypoglycaemia in supratherapeutic doses. Again, in paediatric overdose the full opioid effects of tramadol are seen, though again these respond to naloxone.
Tapentadol is an interesting one for the toxicologists out there – it has a 40% mu opioid load in comparison to pure agonists. Tapentadol toxicity may mimic presentations related to ice, and once again children can have the full spectrum of opioid effects including miosis. There’s really no data regarding the use of naloxone in overdose so it may be worth a try.
In summary, if opioid or atypical opioid overdose is suspected with miosis presenting, it’s probably worth trying naloxone to reverse the opioid effects.
Analgesia goes hand-in-hand with procedural sedation in ED – A/Prof Palmer gave some quick tips for intranasal fentanyl administration. In prehospital care and in many EDs we use the mucosal atomiser device (MAD); this should be angled at 45% for turbinate coating – not horizontal as you’ll get runoff of the meds into the pharynx. Intranasal administration avoids the peaks seen with IV admin and thus reduces the risk of respiratory depression.
In anaesthetic premed, alpha-2 agonists are being used more for over benzodiazepines; they are less amnesic and have the added benefit that the child remembers behaving well so may be better prepared for future procedures. Examples include clonidine 2-4mcg/kg PO, sublingual, transbuccal or IV or Dexmedetomidine 2-4mcg/kg IN (which is becoming cheaper). Dexmedetomidine may cause a 10-15% decrease in PR and BP but is generally well tolerated if the patient is not critically ill. It provides analgesia, anxiolysis, sedation, and behavioural modification which might all be helpful in getting the patient through the CT or MR scanner.
A talk on paediatric analgesia and sedation wouldn’t be complete without a mention of ketamine; sublingual wafers are now available and are expensive but likely to become cheaper. The PO solution can be used as premed; there were PO lozenges available but these had heat stability issues. As we know, ketamine is generally used via the IV route in ED.
An alternative we might start to see more is Buprenorphine sublingual. It comes as a dissolving tablet at low cost, has a 10min onset at 4-6mcg/kg SL 2-4hrly. What’s not quite clear yet is the ceiling for respiratory depression or whether children are not resistant to naloxone following buprenorphine (as adults are).
A/Prof Palmer’s final predictions for the shape of analgesia and sedation in the future were:
- Reduced use of nitrous oxide (greenhouse gas concerns)
- Less methoxyflurane use – occupational exposure
- Increased use IN fentanyl
- Likely increased IN dexmedetomidine and buprenorphine SL
Chris Walker – ARDS
This was a really interesting and philosophical talk that boiled down to whether acute respiratory distress syndrome is a discrete entity (spoiler – no) or in fact a poor and broad descriptor for a group of phenomena (spoiler – yes).
After exploring the history of the diagnosis itself – and the evolution of the use of PEEP in ventilating critically ill patients – Dr Walker pointed out that we are describing mixed “causes” of ARDS – some are pulmonary, others very clearly separate pathologies. How does this stack up?
COVID-ARDS we now know to be a bit different from normal ARDS, particularly in that it responds to steroid unlike “normal” ARDS. A different entity but then perhaps there is different pathophysiology – so why are we mixing the definitions? Similarly, SARS would have been classified as ARDS – and MERS too, if the virus had not been identified.
So when we have a clear underlying diagnosis, we tend not to call it ARDS, which means we might be “under diagnosing” ARDS – but does under-diagnosis matter? It might mean we fail to use lung-protective ventilation with lower TVs in our critically ill patients, but increasingly that’s not my experience.
Dr Walker pointed out that the treatment of ARDS – ventilation strategies, proning, oscillation, NM blockade, ECCO2, ECMO – consists of strategies to help patient stay alive, seemingly irrespective of whether it’s ARDS or you just say it’s ARDS. So if not diagnosed, does it matter? Probably not as good ICU principles are similar.
So is it a thing? Yes; if the patient has respiratory failure with CXR changes in acute setting; as a discrete entity, probably not, but so what? ARDS isn’t a disease, it’s a consequence of many different things and as such a single solution won’t be found because we are looking in the wrong place. Dr Walker’s analogy was that it is the opposite of the blind men describing the elephant – we are all trying to describe a single entity when in fact it is many entities.
I’m not sure how much I took away practically from this session – but a good brain stretch around the nuance of diagnostic categorisation and how much it really matters is always refreshing.
Angela Chiew – Toxicology in PED
Dr Chiew is a powerhouse of toxicology in NSW, where tox is regarded much more the domain of the Emergency Physician than I ever experienced in the UK.
She took a case-based journey through some common poisonings and overdoses in children.
As above, we tend to see a bimodal distribution of toxicology presentations in paediatrics:
- Toddlers – inquisitive, generally small doses, exploratory ingestions (but can be dangerous)
- Adolescents – self-harm or social experimentation
She notes we’ve also seen increased self-harm in adolescents over last 10y, and also that self-harm increased risk of later mental health problems and completed suicide in later life. The toxicology service locally has seen increased calls for advice [rather than toxbase, in NSW tox advice comes primarily from a call to a toxicologist-staffed 24h helpline] related to both recreational drug use and toxicological self-harm since the start of the pandemic.
The study also shows a dramatic increase in self-harm in those born after 1997 – this has been seen in other western countries (UK, USA) and tends to be female-predominant. For paediatric toxicological self-harm, the most common substances are over-the-counter analgesia, followed by prescribed analgesia and psychotropics. Paracetamol, ibuprofen and then fluoxetine are the top 3 agents seen.
There are some changes coming regarding the way we use activated charcoal in ED, with an updated international guideline due in 2022.
Essentially, we can now give within 2h if indicated (previously 1h), within 4h for modified release ingestions and even after a greater time in cases of severe poisoning or if the patient is intubated. The rationale behind this comes from a Japanese study of 160 overdose patients – the patients were consented for gastroscopy (?!) and the endoscopist looked to see if tablets still visible, finding them tablets present up to 12h after ingestion (especially when the agent was modified release or combined with ingestion of an agent slowing ingestion, such as an anticholinergic or opioid).
When deciding whether to give activated charcoal, consider:
- Agent, dose ingested and time elapsed
- Potential complications of ingestion vs activated charcoal
- Availability of antidotes or supportive care
When we call the helpline, we would usually get one of three outcomes related to activated charcoal: don’t give it, offer it to the patient or give in best interests with duty of care. The advice to offer is usually where there is potential toxicity but not severe, so the patient can give informed consent to take or not. Examples include when activated charcoal may decrease length of stay, decrease the need for invasive treatment, or decrease the need for a specific antidote.
When the advice is to give in the patient’s best interest under a duty of care, this advice might be given in the case of severe toxicity such as verapamil or colchicine, or in massive ingestions where it’s the dose that makes the poison. Activated charcoal may be of benefit for paracetamol, aspirin, or modified-release preparations of some medications (eg metformin, paracetamol, citalopram, venlafaxine, digoxin).
Charcoal isn’t needed for everyone: however there are some who may benefit. It’s of lower risk in the awake and alert patient, and there’s no one-size-fits-all algorithmic approach; we need to consider risks and benefits in each case.
Dr Chiew also outlined a basic approach to paediatric toxicology – or potential toxicology presentations.
- Symptom onset
- What meds are in the house? Get a list from everyone
- Consider non-accidental injury/ingestion
- Vital signs
- Pupil responses and muscle tone (these may help identify specific toxidrome)
- Urinary drug screen has limitations (and is infrequently performed in the UK, but more commonly in Australia).
The most frequently used urinary drug screen is immunoassay: this will detect substances above a set threshold using antibodies. The test gives lots of false positives. Unexpected results (in kids or if there are legal implications), can be confirmed with gas chromatography mass spectrometry or high-performance liquid chromatography. This doesn’t give false positives but may give false negatives, particularly for GHB.
Anticholinergic toxidrome can be seen with over-the-counter sedating antihistamines in kids.
- Monitor and treat urinary retention
- Nurse in quiet area
- Supportive care
- Benzodiazepines for agitation
- Physostigmine (0.02mg/kg slow IV) works well for pure anticholinergic toxicity (if you can get it); it’s a reversible inhibitor of anticholinesterases, increasing level of ACh at synases serving as an antidote for anticholinergic syndrome. Unlike neostigmine, physostigmine crosses the blood/brain barrier. It can cause seizures and/or cholinergic toxicity (hypersecretion, bronchospasm, bradycardia)
Opioid OD in kids is relatively straightforward as if the child was opioid naïve you can’t overdose with naloxone: you can give lots! If the agent in question is a long acting opioid, the child may may need infusion. Aim for awake with good respiratory rate – a bit different from the accidental OD in the dependent patient we are more used to treating.
Generally the patients need to be off naloxone for 4h before discharge – and don’t discharge these patients at night.
Some opioids are worth a specific mention; methadone is a synthetic opioid that won’t appear on UDS unless specifically requested. It has a long half life with dose-dependent QT prolonging effect (overdose is associated with lots of cases of torsades de points especially in adults).
Oral naltrexone 1mg/kg (up to 50mg) could be used as a substitute for naloxone – very safe, no side effects in opioid naïve patient (tablet dissolved in water) – may allow for stopping naloxone infusion and bservation on ward Naltrexone is a pure opioid antagonist with a time of onset 15-30mins. It lasts between 4-190hrs with median of 22h; peak effect is seen in 24-72h. This Iranian study showed no further naloxone doses were needed.
Clonidine is used in ADHD, and the service in NSW is commonly contacted for advice following accidental overdoses in siblings. Clonidine has a rapid onset of action within 30-60mins; its effects last 24h. 10mcg/kg can cause toxicity so even accidental double dosing can have effects.
The child with clonidine overdose typically presents with pinpoint pupils, bradycardia, drowsy/fluctuant GCS, hypothermia, rarely seizures. There’s a nice paper by Geoff Isbister (also of NSW toxicology fame) describing clonidine overdose in adults: length of stay was approx. 1 day due to symptom persistence for 24h. Intubation is rarely needed but bradycardia is very common.
Management of clonidine overdose is essentially good supportive care. Dr Chiew advises only treating bradycardia if the patient is hypotensive: then try fluids and atropine if the patient doesn’t respond. There’s some evidence that high dose naloxone might reverse respiratory depression from clonidine – for example, if the patient is so affected that you are going to intubate, trial high dose naloxone first (but only around 1 in 10 responds per the Isbister paper).
Guanfacine has been also used for ADHD, though less commonly – in overdose it behaves like a longer acting version of clonidine; it’s a similar presentation but lasts longer.
There has been a notable increase in SSRI overdoses seen in adolescents: usually this is a single ingestion, which leads to mild toxicity. Citalopram and escitalopram may prolong the QT in overdose. Citalopram and fluvoxamine can cause seizures.
You can access my Serotonin Syndrome versus Neuroleptic Malignant Syndrome Evernote (FRCEM revision) here.
The most severe manifestations tend to be seen in SSRI+MAOI or SSRI+SSNI.
The one you need to know for your exam is cyproheptadine – it relieves symptoms, administered 12mg PO then 8mg TDS. It doesn’t actually abbreviate the course of the overdose-related illness but provides it symptomatic relief while symptoms persist.
If cyptoheptadine is hard to come by, you can use chlorpromazine 25mg-100mg IV for moderate symptoms: but be aware, chlorpromazine can cause hypotension and drowsiness (so consider preloading the patient with IV fluids).
Lastly, Dr Chiew took us through the updates to the paracetamol guideline, structured around answers to the key questions clinicians might have:
- Do I need to offer charcoal? Yes if the patient is awake, alert and cooperative, if they’ve taken immediate release paracetamol of 10-30g and are within 2h post ingestion or if they’ve taken >30g and are within 4h post ingestion
- Do I need to start acetyl-cysteine? The real question here is “can I get a paracetamol level within 8h of ingestion?” If not (eg the patient is presenting at 6h post ingestion or you have limited pathology services), start NAC immediately. Glutathione stores – which are key to metabolising paracetamol – will have depleted by 8h post ingestion, hence the cutoff
- If level is back, use nomogram ONLY for immediate release with known time of ingestion (go by the earliest possible ingestion time)
- In the event of a massive ingestion: if the initial paracetamol is high (eg double the nomogram line), they get an increased dosing for the 2nd bag – and if triple the nomogram line, tox may advise higher doses
- Modified release paracetamol? The nomogram can’t be used. Levels guide treatment only: for example, the need for further decontamination and the need for further NAC.
- For modified release paracetamol ingestions, all patients get activated charcoal within 4h, all >10g start AC, if >30g or >500mg/kg OR paracetamol concentration double the nomogram: increase NAC (liver injury was still being seen and presumed to be related to underdosing)
- Across Australia we have moved to a 2-bag regimen for NAC (rather than the traditional 3-bag regimen): this is associated with fewer adverse reactions and is less confusing
That’s What Happened on Day 2
A final post to follow with my notes from Day 3.
You can find the notes from Day 1 here.