PEM adventures chapter 3

Cite this article as:
Team PEM Adventures. PEM adventures chapter 3, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.31888

It’s time for another PEM adventure. Join us on another journey (with an inbuilt time travel machine) in managing Francesca, a teen who dreams of being a pop star…

Meet Francesca, a 15 year old girl who dreams of being a pop star.  She is making ripples in the world of teen music videos and has a HUGE audition tomorrow for a music video. But for the last 24 hours she’s been feeling a little shaky and pretty nauseous. Putting it down to nerves, her mother (who is also her agent) continued packing for the big trip. But Francesca vomited, had two episodes of diarrhoea and then spiked a fever and her mother knew she needed to get her fixed. Fast.

It’s the middle of a run of the mill shift for you. You’ve just fished a bead from a child’s ear, reduced a decently angulated forearm fracture and admitted a child with a pyelonephritis. When you take a look at Francesca though you know she’s sick. She is agitated, clammy and flushed, and febrile at 39.3°C. She’s tachycardic at 130, with a bounding pulse, blood pressure of 128/74 and normal heart sounds. She tachypnoeic at 24, with sats of 98% in air and a clear chest. Her abdomen is tender in the epigastric region, with no guarding or rigidity. Her GCS is 15 with no focal neurology. Her triage weight is 44kg.

You grab the sepsis trolley. Cannula in you, send some bloods: FBC, coagulation, CRP renal and liver function and blood cultures. You run a venous gas and this is what you see…

That lactate is horrific. You hastily prescribe a 20ml/kg bolus of 0.9% saline and a broad-spectrum third-generation cephalosporin. But, what’s your next step?

You prescribe some paracetamol. Easy enough. And then you go back and think about what to do next.

Close the tab and have a think about some more choices or move on to the next section.

You give another 20ml/kg of 0.9% saline and reassess.

Her heart rate drops down a couple of beats per minute but it bounces up again. So you give more saline. But her heart rate goes up a bit higher. And higher again. She begins to hyperventilate. Heart sinking, you repeat her gas. Her pH has dropped, her lactate has climbed and her potassium looks horribly high. This was NOT supposed to happen. The saline has done exactly the opposite of what you’d like it to do… how could that be? 

You wish you could go back in time and make that choice again. Luckily for you, that’s exactly what the inbuilt time travel machine is for.

Close the tab and take another look at the choices. If there’s nothing else you’d like to do then move on to the next section.

You give another 20ml/kg, but this time, instead of reaching for the saline, you go for Plasmalyte (or Hartmann’s, if that’s your fluid of choice). You reassess. Her heart rate drops down a couple of beats per minute but it bounces up again. Her pulses remain bounding, BP holds and JVP isn’t raised with no rales in her chest so you give another bolus and reassess. Same thing happens: a miniscule response but nothing substantial. You don’t make things worse, but you can’t seem to make things better either. Why isn’t fluid bringing down Francesca’s heart rate?

Close the tab and take another look at the choices. If there’s nothing else you’d like to do then move on to the next section.

Her ECG shows a sinus tachycardia. She’s in sinus rhythm with a p wave before each QRS and a normal p wave axis; her QRS axis is normal and intervals are normal too. There are no voltage criteria for ventricular hypertrophy and you can’t spot any subtle ST changes or delta waves. You use a handy ECG proforma to double check, but apart from the tachycardia, it all looks fine. So you go back to Francesca and have a think about what to do next.

Close the tab and take another look at the choices. If there’s nothing else you’d like to do then move on to the next section.

You have recently been on a POCUS course so you want to try out your ultrasound skills. You ultrasound her abdomen. It looks normal. The eminent professor of ultrasonography wanders by. You ask him to double check your findings. He agrees, ultrasound is normal. 

Close the tab and take another look at the choices. If there’s nothing else you’d like to do then move on to the next section.

While you’re pondering what to do, you receive a phone call from your bank. It’s noisy in ED so you pop into the corridor. The bank tells you they’ve just realised they owe you a couple of hundred pounds (*replace pounds with Euros, Dollars, Australian Dollars or any other local currency). That’s great news! Smiling, you type out a quick text to your best friend. “Epic windfall. Celebrate later in China Town?” You can almost smell the chow mein. Your stomach rumbles. It’s definitely time for some lunch. You let Francesca’s nurse know you’re going for a break.

Just as you’re finishing your sandwich, Francesca’s nurse comes rushing to find you. What with the phone call, the texting and the lunchtime queue in the canteen, it’s been almost three quarters of an hour since you last reviewed Francesca. She is far more agitated. The monitor is alarming. Her temperature is now 40.2°C and she’s very sweaty. She looks a little blue. With a heart rate of 159, BP of 108/72, respiratory rate of 32 and O2 saturations of 93% in air, things are not looking good.

Her mother wails, “Will she be better for her audition?!”

You repeat her gas. It’s not good – her lactate’s now 9.3 and her pH is down to 7.03.

Her nurse hands you an ECG. Scanning it you spy peaked T waves, wide QRS complexes and a prolonged PR.

Hang on! What was the potassium on that gas?! You snatch up her gas – her potassium’s 7.2! How are you going to bring that potassium down? What will you prescribe first?

This is a great first choice. Calcium gluconate stabilises Francesca’s cardiac membrane, buying you some time. The gluconate’s in. But that potassium still needs to come down. How are you going to do that?

Close the tab and choose a second drug or drug combination to bring that potassium down. If you’ve already done that and you’re happy with your choice then move on to the next section.

Fabulous! Sodium bicarbonate is an ideal drug in a child or young person who has hyperkalaemia AND acidosis (but you might want to stabilise the cardiac membrane first, if you haven’t done this already). You prescribe a sodium bicarbonate bolus once Francesca’s had her calcium gluconate and ask your amazing resus nurse to start to prepare for an insulin and dextrose infusion.

Close the tab and move on in the story.

On goes the salbutamol nebuliser while the infusion is drawn up. Up goes the infusion. But then something terrible happens. Francesca’s heart rate climbs higher and higher. And then higher again. Her pulse is thready, she’s more diaphoretic. You didn’t think it was possible but she looks even worse. A repeat ECG confirms your worst fears: she’s in SVT. 

Let’s jump back in that time machine and try that vote again. Close the tab and have a look at your other options.

Insulin and dextrose sounds like a good choice. But do you want to give it as your first line agent to bring Francesca’s potassium down? Or after something else?

You get out your phone – there must be an app there somewhere that tells you how to prescribe insulin dextrose infusions for hyperkalaemia. After much tapping and scrolling you find what you’re looking for and write it up. Your amazing resus nurse starts making up the infusion. 13 minutes later it’s up and running. But it’s too late. Francesca’s potassium has continued to climb and she’s going into a VT arrest. No!

It’s time for the time machine. Close this tab and click on “after something else”

This sounds very sensible. After all, insulin-dextrose infusions can take ages to draw up and you need to give something that will work quickly to stabilise her myocardium as well as something that will help drive the potassium back into the cells.

Close the insulin and dextrose tab and choose two drugs: one to stabilise the myocardium and one to bring down the potassium. Hint: she’s acidotic.

Phew! Francesca’s ECG rhythm is improving. Crisis averted. Or is it?

By now Francesca is so agitated, it’s becoming impossible to keep her in bed. “I have to rule out an intracranial infection”, you think to yourself. She needs a CT.

Her nurse begs you to give her a sedative. This makes you a little anxious (pun totally intended). You know that sedation in a sick child can be lethal. So, how will you manage her agitation?

You don’t want to risk giving her a sedative. You’re quite fond of being a doctor and this is a high stakes situation – you don’t want to lose your medical licence if she arrests. Her nurse rolls his eyes – you’re not the one trying to hold her in bed. But as Francesca rips out her cannula and throws herself against the wall you come to the realisation that you are going to have to prescribe something.

Close this tab and go back to choose a sedative.

You like ketamine, you use it a lot and it’s got an excellent safety profile, right? You give Francesca 1mg/kg. She drifts off into a dissociative state. Unfortunately you weren’t as right as you thought. Because it inhibits reuptake of catecholamines it tends to push heart rates up. Francesca becomes extremely tachycardic. After 20 minutes she starts to develop emergence phenomena and becomes even more agitated. She arrests. But don’t worry, we’ve given you a time travel machine for this very reason.

Close the tab and go back to make a different choice.

Unfortunately haloperidol, like Olanzepine, lowers seizure thresholds. You remember this just as it’s infused. Francesca starts fitting. And to make matters worse, it has also prolonged Francesca’s QTc. Her cardiac rhythm becomes unstable and she arrests. Not what you intended. You hop in your time travel machine and go back to make that choice again.

Close the tab and go back to make a different choice.

Unfortunately Olanzepine, like Haloperidol, lowers seizure thresholds. You remember this just as it’s infused. Francesca starts fitting. And to make matters worse, it has also further prolonged Francesca’s QTc. Her cardiac rhythm becomes unstable and she arrests. Not what you intended. You hop in your time travel machine and go back to make that choice again.

Close the tab and go back to make a different choice.

You give Francesca a nice calming benzodiazepine. She settles, buying you some time.

Close the tab and read on to the next part of the story.

You want Francesca out of ED – this is too stressful! Thankfully PICU have a bed. You compassionately explain to Francesca’s mum that the PICU team will work very hard to treat Francesca but she’s very, very sick. Her mum starts crying, “She’s such a beautiful girl! She was going to be famous! She’s worked so hard to lose weight for her audition!”

Internal alarm bells start ringing. “Hang on! How has she lost weight?” Eyes wide, you ask her mother, “Has she been taking something?!?”

Just as you garble this, Francesca’s dad arrives. He’s found a bottle of pills in Francesca’s room. The label says DNP. They were next to her exercise bike.

You ask switchboard to put you through to the national toxicology advice line. The toxicologist who answers the phone tells you that DNP, short for dinitrophenol, is a diet pill that’s illegal in most countries but quite freely available over the internet. It’s called a fat burner because DNP short circuits mitochondrial ATP production by uncoupling oxidative phosphorylation. Because ATP can’t be produced, metabolic rate increases and energy is instead released as heat. People who take it literally burn fat. But even a single pill can lead to uncontrolled hyperpyrexia and its toxic effects are increased with exercise.

They tell you that Francesca’s bloods must be monitored closely; her liver function will deteriorate as her liver literally cooks from within; she will become hypoglycaemic as her glycogen stores are consumed; and she’ll become hyperkalaemic. Monitor her methaemoglobin and if it reaches 30% or if there are signs of tissue hypoxia, give methylene blue.

They give you a long list of treatments including…

Cold intravenous fluids…

…ice packs…

…gastric and bladder cold fluid lavage with peritoneal cooling if you can…

…and Dantrolene…

…and if that fails… then a cooling heat-exchange central line… or ECMO if you’re really stuck.

That temperature just has to come down.

You thank toxicology and replace the handset and think to yourself, “Now where will I find Dantrolene?”

But while you’re pondering this, things go from bad to worse. Francesca’s temperature continues to climb. She’s now 41°C. She’s boiling. Sweat drips onto the sheets. She starts to have a generalised tonic-clonic seizure. You give her a dose of IV. Lorazepam but she continues to seize.

What will you give next?

But a second benzo doesn’t do the trick. She continues to seize. What will you give next?

Close the tab and have another look at the options.

Phenytoin seems like a sensible idea. It’s the second line anticonvulsant in APLS after all. You prescribe 20mg/kg and the infusion’s set up. But it wasn’t a sensible idea. In fact, it was a terrible idea. The phenytoin has exacerbated sodium channel blockade, making her QRS becomes extremely wide. Despite your best efforts to manage her arrhythmia she arrests. It’s time for the time machine. Let’s go back in time to try that one again.

Close the tab and take another look at the options.

You decide to avoid phenytoin because in the context of a toxin you were worried it would prolong her QTc and make her arrest. And ECLIPSE and CONSEPT showed it’s non-inferior to phenytoin in the management of seizures. It’s a good choice.  Her seizure stops.  What a relief.

Close the tab and move on in the story.

You decide to avoid phenytoin because you were worried its sodium channel blocking properties will widening her QRS complexes and make her arrest. And you’ve heard phenobarbital remains the second line recommended treatment in seizures secondary to recreational drugs. It’s a good choice.  Her seizure stops.  What a relief.

Close the tab and move on in the story.

Things can’t get any worse, right? Wrong. She is making a funny snoring noise. You’re really worried about her airway. You fast bleep the anaesthetist. Finally something’s going right, he’s just walking past, and he’s in resus in less time than you can say “dinitrophenol.” He’s up to speed in no time, and definitely agrees she needs a tube. Your RSI cocktail of choice is ketamine (1-2mg/kg), fentanyl (1mcg/kg) and rocuronium (1-2mg/kg). It’s the least cardio-unstable combination of drugs and you definitely don’t want to make things worse. (Take a look at ‘The curious incident of the wheeze in the night time’ for more on this.) But, luckily for you, the  anaesthetist is a clever guy and says, “Let’s avoid fentanyl since she’s hyperpyrexic as fentanyl’s serotonergic – we don’t want to raise her body temperature any higher than it is already.”

The resus nurse mishears his instruction and almost makes a fatal mistake. Spying a syringe labelled suxamethonium, the anaesthetist (who you decide is your new best friend) calmly says, “No suxamethonium. Her potassium is high. She’ll arrest with sux.”

He intubates successfully using midazolam, propofol and rocuronium.  She’s easy to ventilate.

Finally Francesca’s ready for PICU. With cold fluids, ice packs and Dantrolene her temperature comes down to 37.9 °C. You hand her over with clear instructions to avoid…

…serotonergic drugs (put away that fentanyl)

… or drugs that prolong QRS (don’t even think about phenytoin if she fits again)

…and to set up ECMO if her temperature climbs again.

18 months later you watch Francesca perform live in Eurovision. She receives “Douze points!” from every country, setting the record for the highest ever Eurovision score. She campaigns for better awareness of body image in girls and is vocal about the dangers of diet pills.

But let’s hop back in that time travel machine one last time and see what your learning was from her case…

You find this review article about DNP.

Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J Med Toxicol. 2011;7(3):205-212

Fascinatingly, as well as all the clinical management advice you received from your friendly toxicologist, it also tells you a bit about the history of DNP. You’re intrigued to read that the first death from DNP was over 100 years ago in 1918 secondary to occupational exposure of DNP powder.  It was used in France for the manufacture of munitions during the First World War.  In 1933 it was discovered that human consumption led to significant weight loss. It became very popular as a weight-loss drug but within 5 years it was recognised as being extremely dangerous and was labelled as “not for human consumption” by the FDA in 1938.  Anecdotally, it was prescribed to Russian soldiers during World War II to keep them warm.

It all went wrong in the 80s (didn’t it all?).  An American doctor prescribed DNP tablets to thousands of patients through his private weight loss clinic.  In 1986 he was convicted for drug law violations, fined and prohibited from dispensing DNP to patients.  But this didn’t stop him.  He was eventually jailed for fraud in 2008. But DNP is still out there and sadly widely available on the internet…

So, what has Francesca’s case taught us (aside from reminding us how very cool the Eurovision Song Contest is)?

1. Infection isn’t the only cause of fever

Keep your differentials open. You only need to Google ‘differentials fever + tachycardia’ and the first thing that pops up is a 2013 article titled, ‘Intoxications Associated With Agitation, Tachycardia, Hypertension, and Fever: Differential Diagnosis, Evaluation, and Management.’ (True as of 1st November 2020). Toxicological agents include drugs that cause:

  • Serotonin Syndrome: some antidepressants including SSRIs, SNRIs and lithium, anticonvulsants such as valproate, analgesics such as fentanyl, antiemetics such as ondansetron and street drugs such as cocaine, ecstasy, methamphetamine and LSD.
  • Neuroleptic Malignant Syndrome: ‘typical’ antipsychotics such as haloperidol, newer ‘atypicals’ such as risperidone and olanzepine, antiemetics such as metoclopramide and promethazine.
  • Malignant Hyperthermia: an inherited skeletal muscle disorder triggered by inhaled anaesthetics, succinylcholine, heat or exercise.
  • Sympathomimetics: cocaine, ketamine, ecstasy, amphetamines, synthetic cannabinoids.

Toxicology isn’t where it ends though. In our COVID world we’ll be used to including inflammatory syndromes like PIMS-TS to our list of differentials, but don’t forget other inflammatory syndromes including inflammatory bowel disease and rheumatological; oncological presentations; intracranial causes (bleed, tumour, basically anything that damages the hypothalamus can dysregulate temperature control); endocrine causes like thyroid storm, adrenal crisis… and the list goes on.

2. Engage your toxicology colleagues early

Even if you don’t think the primary cause is toxicological, as soon as it could be then pick up the phone to your regional / national toxicological service. Sedatives, anticonvulsants, anaesthetic induction cocktails… there are many ways things can go wrong. Ask a friend for advice before prescribing drugs in a potentially unstable situation.

3. Familiarise yourself with the management of acute behavioural disturbance

Acute behavioural disturbance can be a very challenging situation to manage. RCEM, the Royal College of Emergency Medicine in the UK, has a short guideline explaining the pros and cons of the different drugs of chemical restraint. Although not specifically tailored to paediatric presentations, the explanation of the drug side effects is a useful guide to frame your management. From a paediatric perspective, NICE (The National Institute of Health and Care Excellence, UK) have a pathway specific for children. If behavioural techniques don’t work and you need to move onto a pharmacological approach, NICE only advocates the use of IM lorazepam. The Royal Children’s Hospital in Melbourne’s ‘Acute Behavioural Disturbance: Acute Management’ CPG has an escalation ladder from behavioural management, to oral, then IM / IV medications, clearly stating antipsychotics should only be given to children who have previously taken antipsychotics or who have a normal ECG. Read it in conjunction with the RCEM guideline to understand the risks of each drug.

4. Think about the approaches to managing fever

We love a bit of paracetamol or ibuprofen to bring down a fever. But do you know how they work? Although paracetamol’s been used for over 100 years, we’re still not entirely sure how it works. Its antipyretic actions are thought to be due to inhibition of prostaglandin synthesis, resulting in a reset of the temperature centre in the hypothalamus. Nonsteroidals, such as ibuprofen, also inhibit prostaglandin production, although via a different cyclooxygenase (COX) pathway (all sounding vaguely familiar?).

However, fever caused by toxins is not caused by prostaglandin or COX inhibition and needs a different approach to resolve.

Start with non-pharmacological measures. Fans, ice packs in the groins and axillae, ice baths and internal techniques such as gastric and bladder cold fluid lavage, or, more invasively, Intravascular Heat Exchange Catheters (the ICY Catheter). The ICY catheter is placed in the inferior vena cava via the femoral vein, acting as an extracorporeal cooling device. Cold saline circulates through the catheter, which is closed so does not infuse saline into the bloodstream, instead returning the now-warmed saline back out of the body. The patient’s core temperature is measured via a thermometer in the bladder and an automated feedback loop between the thermometer and the ICY Catheter ensures the patient’s temperature is brought down to a target range, which can be adjusted by the treating clinician. Add benzodiazepines to prevent shivering and for sedation to help the child or young person tolerate these techniques.

There’s an extremely high mortality in severe hyperthermia – if these measures don’t work then RSI with muscle paralysis (but avoiding suxamethonium), with benzodiazepine infusions.

And reach for the antipyretic drugs. Dantrolene is frequently used in the management of anaesthetic-induced malignant hyperthermia and neuroleptic malignant syndrome. It works as a postsynaptic muscle relaxant, inhibiting calcium ion release and therefore decreasing the amount of excitation-contraction coupling from muscle cells. It’s usually found in theatre, to keep it ready to hand for the treatment of malignant hyperthermia. But, theatre is often far from the ED, and unless you know it’s there, it can take a while to hunt it down in the hospital – don’t let this delay you using it emergently in ED. Although the use of Dantrolene in DNP toxicity is currently under debate with only a few case reports citing its efficacy in DNP toxicity, its use is still recommended to bring down temperatures above 39-40 °C by Toxbase (the UK National Poisons Information Service) because of the high lethality of DNP.

Other options include Cyproheptadine, a first-generation antihistamine with additional anticholinergic properties and antagonist to serotonin, used in the treatment of serotonergic-driven hyperpyrexia (Serotonin Syndrome). To date, there are no case reports of cyproheptadine being used in DNP toxicity.

And don’t forget to monitor CK and renal function.

5. Consider your resuscitation fluid

You may have heard the phrase ‘(ab)normal saline’ before. Sure, one bolus with 0.9% saline is probably fine, but we should be reaching early for a balanced crystalloid like Hartmann’s or Plasmalyte, and probably from the outset.

Francesca has a pure metabolic acidosis and is trying to compensate by dropping her PaCO2. (Ab)normal saline is 0.9% NaCl – that’s one chloride ion for every sodium ion. Chloride binds with hydrogen to form HCl, hydrochloric acid. Giving Francesca more acid in the form of chloride will plunge her pH lower. This will cause her to hyperventilate to compensate further, which will tire her out faster.

And then Francesca becomes hyperkalaemic. Worsening Francesca’s acidosis by giving more saline will only serve to make the hyperkalaemia worse for a number of reasons, the simplest one being that acidosis drives intracellular potassium to the extracellular (intravascular) space. ‘Why is that?’ you might wonder. Remember, we use alkaline sodium bicarbonate to treat hyperkalaemia by driving potassium into the intracellular space. Giving acidic sodium chloride does the opposite: the hydrogen potassium pump exchanges extracellular hydrogen for intracellular potassium, pushing potassium out of the cell into the intravascular space. Giving acid, makes hyperkalaemia worse. Have a look at this Paediatric FOAM post, ‘Hartmanns in hyperkalaemia: Is that (O)K?’, for a more detailed account as to why we shouldn’t use saline in hyperkalaemic patients.

6. Have a strategy for your emergency treatment of hyperkalaemia

The treatment of life-threatening hyperkalaemia has three facets. All three are important but there is physiological and clinical  merit in doing these in order:

1) Membrane stabilisation

2) Shifting K+ into the cells

3) Reducing total body K+

The first two are the quick fix solutions for the ED. The last solution involves potassium diuresis and haemodialysis or haemofiltration and will traditionally be dealt with on the renal unit or PICU – we will expand on these in a separate blog.

IV Calcium Gluconate

Calcium is vital for stabilising the myocardium. Avoidance of a lethal arrhythmia is our primary concern in life threatening hyperkalemia and so giving calcium first is a priority.

Initial dose: Assuming we have peripheral access the dose is 0.1-0.3 ml/kg IV calcium gluconate 10%  over 10 minutes, diluted fivefold to 20mg/ml. Aim for an ionised calcium >1.15  and repeat if required, remembering that a one-off dose will usually last between 30 minutes to an hour. In the case of persistent arrhythmias or particularly resistant hypocalcaemic state further doses of calcium may be indicated or an infusion can be considered (0.2ml/kg/hr of calcium gluconate 10% diluted as above).

Bicarbonate

It is important to understand that bicarbonate will only work in hyperkalaemia if the patient is in an acidotic state. In this context not all bicarbonate solutions have been created equal.  8.4% bicarbonate is very hypertonic and a number of RCT’s suggest that, if given neat, it will not work in reducing serum potassium levels in hyperkalemic patients. This is thought to be due  to the phenomenon of solvent drag; the hypertonic fluid drags potassium ions to the extracellural compartment due to an osmotic shift. This essentially neutralises the effect a neutral or alkali pH has in the direction of movement of the K+ ions making the overall net shift minimal.

On the other hand, isotonic bicarbonate works in patients in an acidotic hyperkalemic state. Isotonic bicarbonate isn’t commercially available in most UK based hospitals but can be made by diluting each milliliter of 8.4% sodium bicarbonate with 4.6 ml of sterile water for injection or 5% dextrose.  A 1.5% solution of sodium bicarbonate is approximately isotonic. Isotonic bicarbonate can rapidly improve hyperkalemia if the patient is acidotic in three ways: a) by shifting potassium intro the intracellular compartment, b) by increasing potassium diuresis due to alkalosis and c) due to a dilutional effect.  1mmol/kg of isotonic bicarbonate can be given to alkalinise the pH and cause a K+ shift.

Insulin

Insulin shifts potassium into cells by stimulating the activity of the Na+– H+ channel on cell membranes. This in turn promotes the entry of sodium into cells, which leads to activation of the Na+– K+ ATPase, causing an influx of potassium. The decline in serum potassium levels by insulin is dose dependent. Due care must be taken to avoid hypoglycaemia, especially in infants and children with nephropathies.  The doses of IV insulin are as follows:

Neonates: 0.3 – 0.6 units/kg/hour

Children > 1 month: 0.05 – 0.2 units/kg/hour 

Run with glucose 0.5 – 1 g/kg/hour (5-10 ml/kg of glucose 10% via peripheral administration)

Salbutamol

Salbutamol causes a small shift of potassium into cells but a high dose is needed for an adequate effect, around 10-20mg on average. This equates to 4 to 8 back to back nebulised doses depending on the patient’s age. Salbutamol use comes with a caution however; it can both worsen a pre-existing acidosis by driving up lactate (essentially having a neutral effect  on potassium clearance) and will also cause a tachycardia, and in patients prone to arrhythmias, it can cause SVT’s or even VF. It should not be first line treatment, and certainly not before the membrane has been stabilised with calcium nor before the pH has been made less acidotic.

7. And DNP?

DNP toxicity is a well reported presentation to the ED, including a case report of a fatality in a teenage girl, using it as a weight-loss drug

Features usually occur within 4 hours, with agitation, flushing, hyperthermia and diaphoresis. As with Francesca, there may be abdominal pain, vomiting and diarrhoea. There may be yellow discolouration to the skin and urine, which can be confused with jaundice, and rash and desquamation can be a feature, (mis)leading you down the path of toxic shock. The deterioration can be very rapid with grossly elevated temperatures, heart rates and respiratory rates.

And the investigations? A metabolic acidosis secondary to raised lactate, methaemoglobinaemia, hyperkalaemia, hypocalcaemia and hyperglycaemia (at least until glycogen stores become depleted, when the blood sugar will drop).

Have a read of the letter to the editor in response to this case report, two case reports from the States, and a further report from London and decide for yourself whether you’ll be reaching for Dantrolene to treat DNP toxicity.

But, let’s finish on a cautionary tale. Dantrolene can be hepatotoxic so monitor liver function closely. This case report describes a child who developed hepatitis after dantrolene at a pretty low dose.

We would LOVE your feedback about these DFTB PEM adventures so if you can spare a minute, please complete our survey at www.tiny.cc/DFTBpemadventure or use your smartphone to let the QR code take you straight there. We timed ourselves completing it and it takes less than a minute. Thank you.

A HUGE thank you to Dr Laura Hunter, EM and Toxicology consultant at Guy’s and St Thomas’ NHS Foundation Trust in London, UK. As well as a wicked sense of humour, Laura has an encyclopedic knowledge of all things toxicological. Thank you Laura.

And we are absolutely delighted to announce that our friend, Costas Kanaris, has joined the PEM adventures team, bringing with him his wisdom of all things critical care and general brilliance.

References

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Blumberg A, Weidmann P, Ferrari P. Effect of prolonged bicarbonate administration on plasma potassium in terminal renal failure. Kidney Int. 1992;41(2):369-374.

Kim H. Acute therapy for hyperkalemia with the combined regimen of bicarbonate and beta(2)-adrenergic agonist (salbutamol) in chronic renal failure patients. J Korean Med Sci. 1997;12(2):111-116.

Kim H. Combined effect of bicarbonate and insulin with glucose in acute therapy of hyperkalemia in end-stage renal disease patients. Nephron. 1996;72(3):476-482.

Conte G, Dal C, Imperatore P, et al. Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure. Kidney Int. 1990;38(2):301-307.]

Fraley D, Adler S. Correction of hyperkalemia by bicarbonate despite constant blood pH. Kidney Int. 1977;12(5):354-360.

end-stage renal disease. Miner Electrolyte Metab. 1991;17(5):297-302.

Gutierrez R, Schlessinger F, Oster J, Rietberg B, Perez G. Effect of hypertonic versus isotonic sodium bicarbonate on plasma potassium concentration in patients with

DeFronzo RA, Felig P, Ferrannini E, et al. Effect of graded doses of insulin on splanchnic and peripheral potassium metabolism in man. Am J Physiol. 1980;238(5):E421–E427

Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J Med Toxicol. 2011;7(3):205-212. doi:10.1007/s13181-011-0162-6

Allen L. Hsiao, Karen A. Santucci, Patricia Seo-Mayer, M. Rajan Mariappan, Michael E. Hodsdon, Kenneth J. Banasiak & Carl R. Baum (2005) Pediatric Fatality Following Ingestion of Dinitrophenol: Postmortem Identification of a “Dietary Supplement”, Clinical Toxicology, 43:4, 281-285, DOI: 10.1081/CLT-58946

Kim Barker, Donna Seger & Suparna Kumar (2006) Letter To The Editor: “Comment on “Pediatric Fatality Following Ingestion of Dinitrophenol: Postmortem Identification of a ‘Dietary Supplement’””, Clinical Toxicology, 44:3, 351, DOI: 10.1080/15563650600584709

Siegmueller C, Narasimhaiah R. Fatal 2,4-dinitrophenol poisoning… coming to a hospital near you. Emergency Medicine Journal 2010;27:639-640.

Kopec KT, Kim T, Mowry J, Aks S, Kao L. Role of dantrolene in dinitrophenol (DNP) overdose: A continuing question? Am J Emerg Med. 2019 Jun;37(6):1216.e1-1216.e2. doi: 10.1016/j.ajem.2019.03.035. Epub 2019 Mar 23. PMID: 30948257.

Divij Pasrija, Shilpi Gupta, Amanda Hassinger. Dantrolene-Induced Hepatitis: A Rare Culprit in the PICU. J Pediatr Intensive Care 2020. DOI: 10.1055/s-0040-1710496

Van Schoor J, Khanderia E, Thorniley A. Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate. BMJ Case Rep. 2018 Dec 19;11(1):e225323. doi: 10.1136/bcr-2018-225323. PMID: 30573533; PMCID: PMC6303589.

Toxicology – a crash course in accidental overdoses

Cite this article as:
Tessa Davis. Toxicology – a crash course in accidental overdoses, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.17991

Matthew (18 months) is brought into ED by his mum. He was found playing in his grandma’s handbag with what looked to be a pill in his mouth. Grandma has loads of meds in that handbag and it’s impossible for them to work out what is missing. What do you do?

Non-Toxic Exposures

Cite this article as:
Joe Rotella. Non-Toxic Exposures, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.16453

Mary had a little taste…

Common non-toxic exposures (and what to expect)

As clinicians, we will occasionally come across someone with a case of Toxicophobia – the fear of being poisoned. In paediatrics, this usually presents in the parents of a little one who has explored their way into something they shouldn’t have. Whilst developmentally normal, it can be hard to tell what to be worried about (and given the last post, there are definitely things to be worried about!). It may seem that something will surely happen (you can blame television for that feeling), but in many cases, a patient is going to be just fine.

Before looking further into the various substances that can cause problems for our young patients, I thought it would be interesting and a bit of fun to talk about some of the non-toxic exposures the Poison Information Centre receives calls about – sometimes on a daily basis. In the instances where patients and their parents find themselves in front of you, it’s useful to know a little about what you needn’t worry about. Or in some cases, only worry about a little…

 

Topical antiseptics  and hand sanitisers

With all this talk about hand hygiene and killing germs, it’s not surprising that someone would worry about someone getting into one of these.

From a Toxicology perspective, there are two ingredients in these products that can be problematic – the first are quaternary ammonium compounds. A prime example is benzalkonium chloride, found in products such as Dettol. The concentrations for most household products are low (less than 7.5%) and likely to cause GI irritation at best with perhaps a vomit and some diarrhoea so supportive treatment will suffice.

Not surprisingly, deliberate overdoses can be clinically more significant with sequelae including corrosive injury, hypotension, renal injury and aspiration. Hand sanitisers containing alcohol, typically ethanol, and can cause intoxication if a large amount is ingested. In scenarios, where a child has had a taste, lick or swallow, significant toxicity is very unlikely

In the end, Paracelsus still holds true – the dose makes the poison and in the vast majority of these cases, it will not be a problem.

 

Silica gel packets

Containing sodium silicate to prevent excess moisture build-up and food spoilage, these little white packets are everywhere you look in the pantry. It is not surprising people get worried when they read the warning ‘DO NOT EAT’ all over the packet. Fortunately, silica is non-toxic however; it can be a choking hazard so a medical assessment is recommended if there are any signs suggestive of inhalation (e.g. cough, wheeze).

 

Dish-washing detergents

Dishwashing detergents contain soaps to help get rid of dirt and grease but luckily not people. Like other household products, they only cause mild GI upset, a ‘scratchy’ throat and aspiration if vomiting occurs.

 

Toilet bowl cleaners

The usual suspects are the toilet discs (see below). Given their job is to help clean yucky organic matter from the inside of a toilet; these are rather pretty in appearance.

As a parent, I do not know what would horrify me more – my child putting his finger into a disc or into the toilet! Maybe the latter…

These discs contain detergent and perfume but the method of exposure is usually a ‘finger dip’ so minimal exposure occurs. If anything, mild GI upset may occur with a larger ingestion. Important advice for parents is that the next poo might be a more psychedelic colour than usual.  

 

Glow sticks

I suspect the majority of calls come around New Year’s or Moomba (if you live in Melbourne). Glow sticks glow thanks to an ester called cyalume, which luminesces when mixed with hydrogen peroxide. Some products have a plastic casing that contains an inner glass capsule that when broken allows the cyalume (in the glass capsule) to mix with the hydrogen peroxide (surrounding the capsule). An accidental chew will lead to a bitter taste, a dry mouth and perhaps a vomit with some nausea, but not much else.

 

Creams and Lotions

Whilst they keep your skin looking healthy and young, eating these will not do much to your insides apart from a GI upset. Some of these contain small amounts of ethanol but normally not enough to cause clinically significant toxicity.

 

Perfumes, colognes and after-shaves

Similar to creams and lotions, these products are often in reach of little hands. Little people often do not drink much, if any, due to their strong odour and taste. Small ingestions are irritant in nature but larger ingestions can result in ethanol intoxication. However a lot of these products can be 60-80% ethanol and given the taste, it would be a very rare event for a child to swallow enough to become intoxicated.

As these are volatile products, off gassing of fumes can occur and causes a chemical pneumonitis in larger ingestions but the taste and smell of these is such that this is a rare occurrence.

 

Pens/Ink

Suddenly I find myself back in high school, swinging from my chair in the back row whilst chatting with friends. The typical patient is a young teenager sucking on a pen. The anticipated adverse effects include discoloration of the tongue, faeces and clothing often with a sense of embarrassment but nothing more.

 

Bubbles

Whilst we ask you not to forget about the bubbles, I’m happy to add ‘Don’t worry about the bubbles’.  These often contain a soap or mild detergent to produce these clear spheres of pure delight so a drink from a container will result only in GI upset and perhaps some irritation if other parts of the body make contact (e.g. eyes). Not to be confused with the champagne variety.

 

Don’t forget to check out the other posts in this series…

Special thanks to Jeff Robinson for his review and input

 

References

Hammond, K., Graybill, T., Spiess, S. E., Lu, J., & Leikin, J. B. (2009). A complicated hospitalization following dilute ammonium chloride ingestion. Journal of Medical Toxicology, 5(4), 218–222. https://doi.org/10.1007/BF03178271

Joseph, M. M., Zeretzke, C., Reader, S., & Sollee, D. R. (2011). Acute ethanol poisoning in a 6-year-old girl following ingestion of alcohol-based hand sanitizer at school. World Journal of Emergency Medicine, 2(3), 232–233. https://doi.org/10.5847/wjem.j.1920-8642.2011.03.014

https://en.wikipedia.org/wiki/Glow_stick

Disclaimer: The information published in this post is for medical education only and does not constitute formal Toxicology advice. The information is current at the time of writing and may change with emerging evidence over time. If you have concerns about an individual who may be poisoned, please call your local Poisons Information Centre (13 11 26 for Australia).

The Toxicological Risk Assessment

Cite this article as:
Joe Rotella. The Toxicological Risk Assessment, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.16255

Hello and welcome to Twinkle Twinkle Little Tox, a new section for Don’t Forget the Bubbles on Paediatric Toxicology!

I’m humbled and honoured to have the opportunity to contribute to this amazing site and join a team of dedicated medical educators. A special thanks to Andy Tagg for the chance and to Shaun Greene and Jeff Robinson from the Victorian Poisons Information Centre for their support in producing these blog posts.

Carbon Monoxide Poisoning

Cite this article as:
Andrew Tagg. Carbon Monoxide Poisoning, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.5361

4 year old Mariska is brought in by ambulance with her mother after being rescued from a house fire.  Neither appear to have sustained any significant injuries as they were woken by the screech of the smoke detector but your resident is worried about possible carbon monoxide poisoning and wants to do an arterial blood gas to rule it out.

Bottom line

  • Carbon monoxide (CO) is an odourless, colourless, tasteless gas that preferentially binds to haemoglobin rendering it unavailable for oxygen transport.
  • CO poisoning in children manifests in a similar fashion as it does in adults but occurs sooner.
  • Capillary blood gases are a lot kinder than arterial blood gases.
  • There is a lack of hard evidence on the best way to treat mild to moderate CO poisoning and no data on long term effects.
  • Prevention is better than cure – fit a CO detector in your home.

How common is paediatric carbon monoxide poisoning?

Every year the newspapers publish heartbreaking headlines about children who have died as a result of carbon monoxide poisoning.   Fortunately these tragic cases are rare. Approximately 450 adults die in the US every year as a result of accidental poisoning but there is no data on the actual number of cases in the paediatric population. There is also little data on the number of cases of exposure and any figure is liable to be a gross underestimate.  It’s a problem that’s rarely on our list of differential diagnoses.

How does CO poisoning manifest in children?

Symptoms can be very subtle and nondescript

  • Headaches
  • Weakness or clumsiness
  • Nausea or vomiting
  • Blurry vision
  • Shortness of breath
  • Flu-like illness

or more serious.

  • Seizures
  • Coma
  • Cardiac arrest

This retrospective case series from Ankara suggested that, as in adults, severity of symptoms relates to degree of exposure, with the worst symptoms to be found with levels greater than 25%.  These affected kids were much more likely to present with neurological symptoms such as headache, syncope or seizures compared to children with lower levels of carboxyhaemoglobin. Because infants and children have a higher basal metabolic rate than adults they are likely to become symptomatic earlier than their parents.  Fortunately this also means they are likely to recover more quickly.

There is also some evidence that poisoning can lead to potential long-term neuropsychiatric sequelae such as subtle personality changes and memory impairment but again paediatric data is lacking.

What's the basic pathophysiology behind CO poisoning?

Carbon monoxide is a byproduct of the incomplete burning of carbon containing fuel.  In most cases of domestic CO poisoning this is as a result of poor or unventilated space heaters that use kerosene or natural gas.

Carbon monoxide exerts its toxic effects via three mechanisms. It preferentially binds to haemoglobin reducing its oxygen binding capacity, it shifts the oxygen dissociation curve to the left thus inhibiting the release of bound oxygen in the periphery and it acts as a direct cellular toxin by impairing aerobic metabolism.

Remember that fetal haemoglobin has a greater affinity for carbon monoxide than adult haemoglobin and so neonates are particularly susceptible.

How is it detected?

Oxygen saturation monitors can be falsely reassuring in the setting of CO poisoning. Carboxyhameoglobin (CoHb) levels may be detected directly from either an arterial or venous blood gas sample with a high degree of correlation between results. A capillary gas is equally as effective and a lot less painful.  Although high levels may give you a diagnosis, partially treated cases may already have low levels.

Small, portable transcutaneous devices also exist but are not readily available in most EDs.

How is it treated?

Whilst immediate first aid involves removing the child from the source, high flow oxygen is the mainstay of treatment.  The half-life of COHb is 320 minutes whilst breathing room air and about 30-90 minutes with an FiO2 of 1.0. With hyperbaric oxygen therapy reduces this time even further to only about 15 minutes  (at 2.5 ATM and 100% O2) though there is controversy over its utility.  We can only extrapolate from adult data as age less than 18 has been an exclusion criteria in all of the major trials.  Whilst there have been positive and negative results the 2011 Cochrane review summarised the results nicely – there’s not enough evidence either way to determine whether HBO reduces the incidence of delayed neuropsychiatric damage.  In the case of moderate to severe poisoning it would be worth consulting your local hyperbaric service.

 

What can you do to make your home safe?

The two basic principles are avoiding it happening in the first place and detecting leaks early. The former can be done by using properly serviced heaters in well ventilated rooms.  The latter can be done by fitting a ceiling mounted carbon monoxide detector.  This device, similar to a smoke detector, emits an ear-piercing shriek if higher than expected levels of carbon monoxide are detected.

Outcome

You convince your resident that although it is possible that Mariska had an elevated CO level when she was rescued, the investigation that they want to do is likely to be more harmful than helpful. You persuade them to do a capillary gas instead and are satisfied with an undetectable CO level.

HT to Charlotte Davies (@OneLongPlait) for the idea behind this post.

 

References
Kurt F, Bektaş Ö, Kalkan G, Öncel MY, Yakut HI, Kocabaş CN. Does age affect presenting symptoms in children with carbon monoxide poisoning? Pediatr Emerg Care. 2013 Aug;29(8):916-21

Vieregge P, Klostermann W, Blumm RG, Borgis KJ. Carbon monoxide poisoning: clinical, neurophysiological, and brain imaging observations in acute disease and follow-up. J Neurol 1989;236:478–81

Suner S, Partridge R, Sucov A, et al. Non-invasive pulse CO-oximetry screening in the emergency department identifies occult carbon monoxide toxicity. J Emerg Med. May 2008;34(4):441-50

Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011 Apr 13;(4)

Life in the Fast Lane Critical Care Companion – Carbon Monoxide poisoning (accessed 1/4/2014)

Weaver LK, Hopkins RO, Chan KJ et al.  Hyperbaric oxygen for acute carbon monoxide poisoning. New England Journal of Medicine 2002; 347(14):1057–1067

Scheinkestel CD, Bailey M, Myles PS et al. Hyperbaric or normobaric oxygen for acute carbon monoxide posioning: a randomised controlled clinical trial. Medical Journal of Australia 1999; 170:203–210

Touger, Michael, E. John Gallagher, and Jim Tyrell. “Relationship between venous and arterial carboxyhemoglobin levels in patients with suspected carbon monoxide poisoning.” Annals of emergency medicine 25.4 (1995): 481-483.

Heidari, Kamran, et al. “Correlation between capillary and arterial blood gas parameters in an ED.” The American journal of emergency medicine 31.2 (2013): 326-329.