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.

Procedural sedation

Cite this article as:
Tadgh Moriarty. Procedural sedation, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.23718

Sometimes we have to do things that children don’t like. These procedures may be scary, or potentially painful. In this post, we’ll cover a few of the more common techniques.

 

Case one: Kayla

Earlier this month, the UK Royal College of Emergency Medicine, RCEM, published new guidance on the use of ketamine for procedural sedation in children in the emergency department, superseding their 2016 guidelines. Follow Kayla through her ED visit as she helps us explore the changes RCEM recommends.

 

It’s 3 pm on a busy Friday afternoon on your PEM shift. You have just seen Kayla, a 20-month-old girl who fell from onto a concrete step and sustained a nasty L-shaped laceration to her thigh. You have satisfied yourself that her joints are not involved, and an x-ray reveals no underlying fracture. You can see a large amount of debris within the wound. Her vaccines are up to date and she has no significant medical history. She is, however, eating a large ice cream cone that her parents had purchased to pacify her. You wonder how best to proceed as you have a nasty wound that needs thorough irrigation and closure. A toddler is unlikely to tolerate local anaesthetic infiltration as the primary means of anaesthetising the wound.

 

Does Kayla need procedural sedation?

Paediatric Procedural Sedation (PPS) aims to alleviate the distress around painful procedures but should not be viewed as a substitute for good pain relief. Maximize analgesia and recruit any distraction devices to hand (iPads / parents / play specialists – these are a particularly excellent resource and should be utilized wherever possible).

Is the wound suitable for ‘LAT gel’? This revolutionary gel which combines lignocaine, adrenaline and tetracaine can prevent many sedations when used correctly. It takes 30-60minutes to be fully effective after application so be sure to allow sufficient time. Even if the patient is progressing to procedural sedation this gel will help with local anaesthesia and analgesia.

The ability to perform PPS will be based on current acuity within the department, available resources, and appropriate staffing skill mix. The three main agents used for procedural sedation in paediatrics are midazolam, nitrous oxide, and ketamine.

 

Kayla’s LAT gel has been in situ for half an hour. You return to the cubicle armed with a play specialist and nurse, along with your irrigation and suturing materials. Despite a stellar sock puppet show by your play specialist, loud sing-along songs, and Peppa Pig showing on the iPad, your attempt at irrigation is futile; Kayla remains upset. You decide PPS is needed to ensure effective irrigation, neat wound closure, and avoiding further trauma to an upset child (and mother!)

 

Which agent is best suited?

You need to consider what you hope to achieve with sedation and what level of experience and resources are available currently in the department to aid in answering this question. The spectrum of use varies from diagnostic imaging, through minimally painful procedures (e.g. foreign body removal, vascular access), to painful procedures (e.g. fracture reduction, wound washout and closure). The choice of agent, therefore, will reflect the individual patient (anxiety, co-operative, parental preference), and the staff available at the time.

 

Kayla requires a short painful procedure to be carried out and nitrous oxide or ketamine would be suitable. As you start showing her the face mask for nitrous, Kayla freaks out – Kayla had a slightly traumatic experience with a bronchodilator and spacer, her mother explains. There’s no way you’re going to get Kayla to cooperate with the nitrous mask. So ketamine is selected as the agent of choice.

Just as you are about to begin the pre-procedure assessment one of the student nurses who will be observing the procedure tells you that she has seen a lot on Twitter about the new RCEM ketamine PPS guideline recently but is unclear as to exactly what ketamine is and why it’s useful in paediatrics.

 

Ketamine is an NMDA receptor antagonist. It is a dissociative anaesthetic and potent analgesic and amnesic. Rather than the typical ‘sleep‘ which results after administration of other anaesthetic agents, ketamine induces a trance-like state, oftentimes with the patient’s eyes open but ‘nobody home‘ (it is important to warn parents beforehand about this as it can be quite scary if unexpected). Some of the many benefits of ketamine are that airway reflexes are maintained, while is augmented heart rate and blood pressure (for the most part – in the compromised circulation bradycardia and hypotension can occur).

 

The pre-sedation assessment

You begin Kayla’s pre-sedation assessment. Your assessment includes a focussed history: has Kayla undergone any previous anaesthesia or PPS? If so, did she have any reactions or adverse events? Does she suffer from any chronic medical conditions, take any regular medications or have any drug allergies? Does Kayla have any concurrent medical conditions – especially active asthma, respiratory tract infection or tonsillitis?

You then examine Kayla, ensuring you conduct as cardiorespiratory exam and an assessment of her airway anatomy, including ASA grade. You need to assure yourself that no contraindications exist.

 

RCEM’s 2020 guidance is very specific about the need for conducting a thorough pre-sedation assessment, including assessing ASA grade, all of which should be thoroughly documented for clinical auditing and safety purposes. An example proforma template is provided at the end of their guideline. This contrasts with the 2016 guideline, which included a list of contraindications, but did not require documentation of ASA grade.

 

It’s time to consent Kayla and her mum for the procedure. You remember that ketamine is considered safer than other hypnotic drugs such as Propofol but need to remind yourself of the specifics, and the side-effect profile prior to consenting.

 

How safe is ketamine?

Does ketamine have side effects? Yes, but of all sedation agents studied by Bhatt et al in 2017 (6,760 patients across 5 sites in Canada), ketamine came out on top. This looked at ketamine/propofol, ketamine/fentanyl, propofol alone and ketamine alone. There were 831 adverse events across all agents (11.7%) – these included oxygen desaturation (5.6%) and vomiting (5.2%). There were 69 (1.1% of cases) serious adverse events (SAE). Ketamine as single-agent had the lowest SAEs at just 0.4%.

Pre-procedural opioids and laceration repair were associated with increased risk of emesis. Bhatt et al noted that prophylactic antiemetics reduce the risk of vomiting by half, but these were not needed in those under 5 years of age due to the low overall risk of emesis.

This endorsed previous data from a large case series by Green et al (2009) which demonstrated low rates of adverse events with ketamine PPS; most notably, noisy breathing (not requiring any intervention other than airway repositioning) occurred in 1%, laryngospasm in 0.3% and of these only 0.02% required intubation.

Both of these large studies demonstrate ketamine’s excellent safety profile when used with the appropriate preparation and patient selection.

 

Does Kayla need to have fasted?

Let’s have a look at the current guidelines and evidence. Several large studies have looked at this controversial issue: one study in a US PED in 2001/2002 where only 44% of patients met traditional fasting guidelines demonstrated no statistically nor clinically significant increase in adverse events in the unfasted population.

A series of over 30,000 children undergoing PPS by Cravero et al (2006) reported only 1 episode of aspiration – and this was in a fasted patient!

In 2016, Beach et al published a report based on 140,000 procedural sedation events, noting that aspiration was a rare event. Furthermore, they concluded that non-fasted patients were at no greater risk of major complications or aspiration than fasted patients.

In 2014 the American College of Emergency Physicians (ACEP) altered their national guidance stating that procedural sedation “should not be delayed for children in the ED who have not been fasted.” This was based on a systematic review including 3,000 sedation events showing that pre-procedural fasting failed to reduce the risk of emesis, aspiration, or other adverse events. They acknowledged that the current evidence does not support the rationale put forth in the non-emergency medicine guidelines that adherence to minimum fasting times decreased adverse events in ED procedural sedation.

 

This is reflected in RCEM’s 2020 guidance, which states that there is no evidence that complications are reduced if the child has fasted. They advised that the fasting state should be considered in relation to the urgency of the procedure, but recent food intake should not be considered as a contraindication to ketamine use.*

 

*We cheered when we read this in the 2020 guideline. No more fasting – we’ve been saying this for years! But, a quick look back at the 2016 guideline shows that this was actually the recommendation back then too. Really careful scrutiny shows that a single word, “however”, has been removed from the start of the sentence, “traditional anaesthetic practice favours a period of fasting”, altering the tone of the recommendation to a much less dogmatic mandate about nil by mouth status.

 

Satisfied that the evidence does not suggest any advantage to fasting children before PPS (who, let’s face it, tend to be less cooperative when hungry anyway), you prepare the room, staff, and equipment for the procedure.

 

Where will Kayla’s procedure be carried out, how many staff do you require, and what equipment should get ready?

 

RCEM recommends at least three operators: the proceduralist (the clinician performing the procedure), the sedationist (clinician responsible purely for managing sedation) and a sedation assistant*. They specifically acknowledge that the clinician responsible for the sedation and the patient’s airway should be experienced in the use of ketamine, and capable of managing its complications. The 2020 guideline has elaborated further on this, coming with a recommendation for a need for suitable training, a minimum of six months’ experience in anaesthesia or intensive care medicine and an up-to-date APLS course.

*RCEM says ‘nurse’ for the third member of staff but really, it’s anyone who is experienced in monitoring children and supporting the sedationist – doctors can take on this role too.

ACEP’s 2014 position statement concurs with the need for three operators.

The recommendation is that the procedure should be carried out in a resuscitation bay or high dependency area with immediate access to full resuscitation facilities.

Monitoring (every five minutes) of heart rate, blood pressure, respiratory rate, and oxygen saturation is mandated. The American Academy of Pediatrics advised the use of capnography as an adjunct in order to detect hypoventilation and apnoea earlier than pulse oximetry or clinical assessment alone. While no evidence currently shows capnography reduces the incidence of serious adverse events, available studies show a decreased incidence of hypoxia and respiratory events.

 

The use of capnography during sedation has been affirmed by RCEM who have made it a mandatory minimal requirement in their most recent guideline iteration, in parallel with their previously recommended monitoring of respiratory rate, heart rate, oxygen saturations, ECG and BP.
The 2020 RCEM guideline also includes ‘degree of dissociative sedation’ as part of its recommended monitoring during the procedure, which is a new addition to their guidance. Ketamine is unique in that it does not conform to the ‘sedation continuum’ – the patient is either dissociated or not. This recommendation is perhaps aimed at prompting the sedation clinician and nursing colleague as to whether dissociation has occurred, and as to whether a top-up dose is required (more on that later).
The updated RCEM document specifically advises having key resuscitation drug dose calculations performed prior to the procedure and ready access to these, another new addition to their guidance, although no specific drugs are recommended.

 

Some doses you may find useful are:

As you’re checking the ketamine and emergency drug doses with your nursing colleague she asks whether you want her to draw up atropine and midazolam? She is a recent addition to the ED team and mentions that when she worked in theatre some years ago they frequently gave these medications together with ketamine.

 

Should any adjunctive agents be used with ketamine?

There was a previous vogue to co-administer a benzodiazepine to reduce the incidence of emergence. A 2018 BestBets review looked at this very question by studying 6 relevant studies (including 2 RCTs: Sherwin et al 2000, and Walthen et al 2000). These failed to demonstrate a significant difference in emergence between ketamine alone and ketamine with midazolam. In fact, the only difference demonstrated was increased rates of adverse advents when a benzo was co-administered. So, no prophylactic benzodiazepine required.

Having said this, if a child suffers severe emergence (older children, in particular, have increased risk of recovery agitation), then it is worth considering midazolam (aliquots of IV 0.05-0.1mg/kg) to treat (but not routinely or for minor / moderate emergence).

Another previous trend involved the co-administration of atropine to reduce the risk of aspiration. But the evidence does not support this practice, Green et al concluded “There is no evidence to support routine use of anticholinergic medication such as atropine to prevent laryngospasm or other adverse airway events.” Concurrent anticholinergics may actually increase the rate of airway and respiratory adverse events. There is a small increased risk of laryngospasm with oropharyngeal manipulation (including suctioning) so atropine (20 micrograms/kg IV) may be considered as rescue therapy if PPS is being used for intraoral laceration repair (although RCEM would recommend not using ketamine for these procedures for this precise reason).

A common side-effect of ketamine is vomiting. RCEM’s 2020 guidance recommends the use of IV ondansetron at 0.1mg/kg (max dose 4mg) to treat intractable vomiting.

Given ketamine’s emetogenic properties, is it worth giving an antiemetic prophylactically? It is worth considering ondansetron (0.1mg/kg IV) as prophylaxis in high risk groups: those with previous nausea/vomiting during sedation/anaesthesia, older children, or IM administration. The NNT depending on age of the patient will lie between Var7 and 9. This was further endorsed by a BestBets review published in the EMJ in 2018 which concluded that ondansetron should be considered when using ketamine for PPS, especially in older children or for those receiving preprocedural opioids. As with any drug, however, you’ll need to balance the risk-benefit ratio in your mind. Some would prefer not to use ondansetron prophylactically because of the risk of arrhythmias in children with undiagnosed long QT. But, again, long QT is rare…

 

A resus bay is prepped. Kayla and her mother are ready. Roles have been allocated; your nursing colleague is ready and is just removing the Ametop from Kayla’s hands which had been applied when PPS was considered; one of the ANPs will be the procedural clinician and your consultant will supervise you as the sedation clinician. You cannulate first go, while Kayla is distracted by Peppa Pig on screen. It’s time to dissociate.

 

But what dose will you give Kayla?

Various opinions exists regarding the exact or perfect dose; the most commonly accepted dosing schedule is 1-1.5mg/kg for intravenous (IV) administration.

 

RCEM’s guideline recommends a starting dose of 1mg/kg over 60 seconds (to reduce adverse events such as laryngospasm). This can be supplemented with top-up doses of 0.5mg/kg. This has not changed from their previous guidance.

 

You should notice onset of action within a minute. It is easy to spot as the child will develop horizontal nystagmus coupled with a loss of response to verbal stimuli. The heart rate, blood pressure and respiration rate may all increase slightly. Sedation will start to wear off after 20 minutes, with full recovery should occur by about 60 to 120 minutes.

Many departments are still using intramuscular (IM) ketamine. This can be particularly helpful in certain situations such as where IV access is difficult.

 

Due to its variable onset and offset time, longer time to recovery and increased risk of emesis, however, RCEM have now advised against IM except where senior decision-makers deem it necessary. The advice is that “clinicians should be mindful of the perceived safety benefits of having intravenous access from the start of the procedure to mitigate a rare adverse event.” This is the biggest change in their new guidance; the 2016 guideline included dosing and top-up recommendations for IM ketamine.

 

There are still some children who would benefit from IM ketamine, so if choosing the IM option, consider a dose of 2-4mg/kg, with senior clinical support. Ideally IV access could be achieved once the child is dissociated and the IV top-up dose can be administered if required. However if IV access is impossible or not obtained the IM top-up dose is 1-2mg/kg. You can expect a slightly slower onset at about 3-5 minutes with its duration extended from 15-30minutes. Recovery is variable occurring anywhere between 60-120 minutes.

 

As you walk over to the drug cupboard to collect your syringes with carefully calculated doses, your consultant asks, “Are you confident in managing any potential airway complications?”

 

Airway complications with ketamine PPS

Thankfully complications with ketamine are rare. Most events such as noisy breathing or stridor, and minor desaturation will respond to simple airway manoeuvres to ensure the airway is open, plus the use of high-flow oxygen via a mask with a reservoir bag. The most feared complication, laryngospasm, is extremely rare and most often will respond to simple airway manoeuvres. But sedationists must be competent in managing this prior to administering the first dose of ketamine. If laryngospasm is suspected, stop the procedure and call for help. Ensure 100% oxygen is administered if not already in situ. Gently suction any visible secretions. If this fails to improve the situation begin manual ventilation with ventilation via a bag-valve-mask or, if you are comfortable using an anaesthetic circuit, apply PEEP. Some guidelines (and anaesthetists) suggest applying pressure to Larson’s point, very similar to performing a strong jaw thrust. If there is no response at this point, with critical airway compromise, then RSI is required. Administer the pre-calculated dose of paralytic and intubate. Remember, Green’s reported incidence of intubation secondary to laryngospasm was only 0.02%.

The flowchart below may be of benefit – it formed part of my quality improvement project on PPS and was used as a wall chart in the sedation cubicle and included in each sedation proforma booklet. When emergencies occur, being able to cognitively offload by following step by step aide memoires and having pre-calculated doses to hand can be immensely comforting and helpful.

 

 

Kayla’s procedure is completed without difficulty and the nurse enquires as to how long Kayla needs to remain monitored for?

 

Children should remain monitored until their conscious state, level of verbalization and ambulation is back at pre sedation levels. They should be able to tolerate oral fluids. Prior to discharge, a final set of observations should be within normal limits for their age. Consider the need for a prescription (antibiotics or analgesia) prior to discharge.

 

Kayla successfully underwent ketamine PPS, allowing a thorough wash out of her wound and suturing which provided a tidy end result. She was later discharged with an antibiotic prescription and a teddy which the play specialist had found in the toy room for her. Delighted with your chance to use “Special K”, you quickly took out your phone to tweet about the latest changes in RCEM guidance in ketamine for procedural sedation in children in the ED (along with the endless uses of ketamine!)

 

The new RCEM guidance has come at an interesting time – how might it change our practice in PPS in the ED? PERUKI are soon to launch a two-level paediatric procedural sedation survey (name PoPSiCLE – we all know that a good study needs a catchy name) to inform the current status and variations in the practice of PPS in PERUKI , to provide baseline information for developing a network-wide training resource and patient registry. Watch this space…

 

Case two: Ronan

 

It’s a sunny Saturday afternoon. The smell of BBQ and summer is wafting through some open windows in the department. On your way to work, you noticed plenty of bouncy castles and trampolines in use. It’s not surprising your first patient is an 8-year-old boy who has fallen awkwardly while trying to impress some other kids at his birthday party. After examining him and his xray you see he has a midshaft radius and ulnar fracture with some angulation. Thankfully his DRUJ (distal radio-ulnar joint) appears intact, and his radial head is in joint. He needs manipulation of the fractures and application of a backslab. He’s in a lot of pain, despite the paracetamol and ibuprofen he had at triage. He tells you his favourite birthday cake is at home waiting for him and he wants to get home to blow out all the candles. You wonder if you can avoid him a trip to the operating room for a general anaesthetic. Would PPS perhaps be a safe alternative?

 

Nitrous oxide provides anaesthesia, anxiolysis, and also some mild amnesia. However, it offers limited analgesia and so co-administration of an analgesic is recommended. Several key papers, including the FAN study (2017) and Seith et al (2012) have demonstrated the safety and efficacy of co-administrating intranasal fentanyl (INF) with nitrous oxide.

Once you’re ready to go, move the child into the dedicated resus bay or sedation room. If using piped nitrous oxide with a variable concentration flow meter (ensuring the scavenging system is switched on) titrate the dose from 30-70% according to clinical response. The alternative is Entonox (a 50/50 mix of nitrous and oxygen) which usually comes in portable canisters but requires the child to be able to take a deep breath to overcome a demand valve circuit, usually tricky for the under-fives. You should notice the onset of effect in 30-60 seconds, but its peak effect will be 2-5 minutes so best to wait for this before commencing the procedure. Once the intervention or procedure is completed it is important to administer 100% oxygen for 3-5minutes post-procedure to avoid diffusion hypoxia. The offset of effects should occur within 2-5 minutes.

Does nitrous oxide have any side effects? While well tolerated by most children, transient minor side effects such as nausea, dizziness and occasionally nightmares can occur. It can cause vomiting in 6-10% of children receiving 50% nitrous dose. This rate increases with higher concentration and can increase up to 25% if an opioid is co-administered. Be sure to warn parents about this relative frequency of vomiting when using nitrous oxide, both during and after sedation. The risk of vomiting also increases with a longer duration of nitrous administration. Consider a prophylactic antiemetic if the child has a history of nausea or vomiting.

Nitrous oxide diffuses through tissues more rapidly than nitrogen alone and can expand in air-containing spaces within the body. This makes it contraindicated for use in patients with gastrointestinal obstruction, pneumocephalus, pneumothorax and after diving.

Nitrous oxide inactivates the vitamin B12-dependent enzyme, methionine synthase, and so can deplete vitamin B12 stores. Because of this, caution is advised in those at risk of vitamin B12 deficiency such as vegetarians, patients with gastrointestinal disorders and those taking regular H2 receptor blockers and proton pump inhibitors. Nitrous should also be avoided in those with metabolic diseases especially methionine synthase deficiency, methymalonic acidaemia, and homocysinuria (because inactivation of methionine synthase can affect homocysteine metabolism). There’s a theoretical risk to pregnancies in the first trimester and so guidance often suggests avoiding nitrous oxide exposure in early pregnancy.

During administration monitor heart rate, respiratory rate and oxygen saturations. At least two staff members are required; a sedationist and a proceduralist.

 

Ronan and his mum are happy for you to use nitrous oxide and eagerly his mum signs the consent form. While setting up the sedation room and recruiting a nursing colleague to assist, you administer intranasal fentanyl. Ronan successfully undergoes manipulation of his fractures and an above elbow backslab is applied. His post-reduction x-ray shows you performed a pretty awesome reduction and, in consultation with your orthopaedic colleagues, you are happy for Ronan to be discharged to return to their fracture clinic in a few days’ time. This delights Ronan, as he gets to return home to his birthday party (with strict instructions to remain off the trampoline) and he promises to bring you back some of his birthday cake later!

 

 

Case three: Chantelle

Your junior colleague has come to you for advice. She has just seen a 4-year-old girl who was hard at work in her playroom creating unicorn pictures. Her mum had given her lots of colourful supplies including some glittery sequins and beads. Chantelle became adventurous and decided to decorate herself rather than the unicorns. Unfortunately, one of the beads has become lodged in her ear and despite an attempt by your colleague using both parents, and a play specialist, the removal of the foreign body was unsuccessful. You believe the use of PPS will be required and begin pondering which agent to use.

 

Midazolam is a hypnotic agent providing anxiolysis and amnesia. It does not have analgesic properties, which is why it is important to co-administer with analgesia for any painful procedure. It can be administered by many routes, the two commonest for PPS being intranasal (IN) and orally. If used intranasally, a dose of 0.3-0.5mg/kg is suggested. You should notice its onset within 10-15 minutes, lasting about 60 minutes. This route of administration can cause some nasal irritation and burning, so some clinicians prefer to use it orally. With an oral dose of 0.5mg/kg you should notice onset at 15-30 minutes with a duration of effect for 60-90 minutes. Midazolam tastes bitter – so give it with some juice or squash to make it more palatable. Midazolam can be given intramuscularly (IM) and intravenously (IV), but it is less likely to be used in this fashion for PPS.

Does midazolam have any side effects? Yes! It can cause hypoventilation and apnoea – be aware that this risk is increased if co-administered with an opioid such as fentanyl or diamorphine. A reversal agent does exist: flumazenil (0.01mg/kg, max dose 1mg) but this is rarely required, and oftentimes using basic airway manoeuvres is sufficient. Paradoxical excitatory or agitation reactions can occur in up to 15% of children. Do warn parents of this possibility prior to administration. The best course of action if it does occur is to let the child “ride it out”. Because of this, many ED clinicians will choose ketamine or nitrous oxide as their PPS agent of choice over midazolam.

With these side effects in mind, it is prudent to ensure basic monitoring includes heart rate, respiratory rate, and oxygen saturation monitoring. At least two staff are required; proceduralist and sedationist.

 

Having obtained informed consent from Chantelle’s mother, you decide to give her intranasal midazolam. 45 minutes later you remove the mischievous bead from her left ear. Her parents are thrilled, but before you leave the room you remember the mantra of “always check the other ear”. So before packing up your tools and leaving her with your sedation nurse, you decide to check her other ear. Interesting you find two glittery sequins hiding in her right ear canal. Phew, that saved a second sedation event!

 

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Pena, B.M. and Krauss, B. Adverse events of procedural sedation and analgesia in a pediatric emergency department. Ann Emerg Med. 1999; 34: 483–491

Wright, S.W., Chudnofsky, C.R., Dronen, S.C. et al. Midazolam use in the emergency department. Am J Emerg Med. 1990; 8: 97–100

Davies FC, Waters M. Oral midazolam for conscious sedation of children during minor procedures. J Accid Emerg Med. 1998;15(4):244–248. doi:10.1136/emj.15.4.244

Graff, K.J., Kennedy, R.M., and Jaffe, D.M. Conscious sedation for pediatric orthopaedic emergencies. Pediatric Emerg Care. 1996; 12: 31–35

Bailey, P.L., Pace, N.L., Ashburn, M.A. et al. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology. 1990; 73: 826–830

Gregory GA. Pediatric Anesthesia. 4th ed. Philadelphia, PA: Churchill Living- stone; 2002

 

Ketamine

Cite this article as:
Jess Longmore. Ketamine, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.10643

You can keep staring at the 3 year old’s deep eyebrow laceration, desperate to glue it, but you know it needs to be sutured. Now what?

Injured or distressed children present us with difficulties in the emergency department. Children experience a more intense physical and emotional reaction to painful or threatening procedures than adults. The goals of sedation of children in the emergency department include minimizing pain, anxiety, movement which may jeopardize the procedure, and maximizing the chances of success for the procedure performed, returning the patient to his or her pre-sedated state as quickly as possible while assuring the patient’s safety. In addition to minimizing the negative psychological experience for the child, sedation will reduce fear and distress in subsequent presentations to health care facilities.

Paediatric procedural sedation has become a domain of expertise in emergency medicine. As emergency physicians, we should be aware of the pros and cons of the different options within paediatric sedation, and not only skilled in the technicalities of each but in the non-clinical aspect of ensuring both the child and the caregiver have as pleasant an experience as possible.

Choice of sedation

There are no hard and fast rules on what sedation to use. One must take into account many variables, including the age (and temperament) of the child, the proposed procedure, fasting time, co-morbidities, and levels of parental anxiety. If a patient or a parent is extremely anxious, or if the procedure has the potential to be very long, complex or painful, it may be more appropriate or kinder for the child to have their procedure done in theatre under general anaesthetic. In a compliant child with a laceration away from the face needing sutures, Nitrous Oxide may be ideal.

Prior to any form of sedation

  • Take time to discuss the options with the parents.
  • Remember to consider systemic pain relief. If using ketamine it is important that the patient is comfortable before the drug is administered – if they are uncomfortable or agitated during administration they are more likely to have nightmares or a scary emergence.
  • ALA (or similar) should be used around wound edges, and AnGel/LMX on potential cannulations sites.
  • Local anaesthetic should be used where appropriate as the analgesic effect will outlast the ketamine.

Ketamine sedation

Ketamine has been described as the “ideal” agent for paediatric sedation, and has rapidly become the drug of choice for short, painful procedures in the ED due to its rapid onset of action, and anxiolytic, analgesic and amnesic properties. Ketamine dissociation results in a lack of response to painful or noxious stimuli, whilst preserving respiratory and cardiovascular stability.

Ketamine use has previously been restricted to anaesthetists, but emergency physicians are using it more and more frequently; ACEM and ACEP both have formal guidelines for emergency physicians especially for ketamine sedations, and most departments will have a local protocol. It should, however, only ever be used in a resuscitation area by an airway trained doctor in case of laryngospasm. It is mandatory to have a separate doctor performing the procedure itself and a nurse credentialed in ketamine sedation. Local policies may specify PLS/APLS certification or similar. This may mean delaying the procedure until daylight hours or calling in the consultant if there is an urgent clinical need.

Absolute contraindication

infants less than 6 months (due to increased risk of airway compromise and recent animal studies which have found that ketamine is involved in neuronal degeneration within the developing brain)

Relative contraindications

  • age less than 12 months
  • high risk of laryngospasm (e.g. asthma, active URTI)
  • significant cardiac disease
  • reduced loc or recent head injury
  • previous psychosis
  • prior adverse reaction to ketamine

Examples of appropriate procedures

  • Suturing
  • Reduction of fractures/dislocations
  • Burn debridement
  • Lumbar Puncture
  • Abscess drainage

For the parents

For successful sedation, it is integral to involve the parents or caregivers and keep them on side. Take the time to explain the procedure to them and gain informed consent. I often given them a leaflet to read about ketamine sedation and then come back ten minutes later to answer any questions they may have. Ensure to go over what will happen, what they will see and what the child will experience.

Examples

  • Your child may seem to be awake after receiving ketamine, their eyes might flicker from side to side or they might twitch – this is normal
  • They may develop a rash
  • They may vomit
  • They may drool
  •  Sometimes as your child wakes up they may be agitated or appear to be having hallucinations or nightmares. These can normally be helped by minimizing sensory input (e.g. talking softly and dimming the lights), but if required we can give a drug that will help to minimize these.
  • In very few cases, we may have to give extra Oxygen or extra drugs
  • Be reassured that your child will not remember the procedure

How parents can help:

Keep calm themselves, reassure the child, talk softly and smoothly and describe a pleasant scene to them as they are given the drug. Remain with the child throughout the procedure and provide positive

Routes of administration

Ketamine can be used intravenously or intra-muscularly, if access is likely to be problem. Studies have concluded that IV ketamine is similar to IM ketamine in terms of efficacy and safety, with no significant difference in the rates of adverse respiratory events, however higher rates of vomiting were found in intramuscular administration.

IM has also been found to last slightly longer, and time to discharge was therefore longer (129 minutes from administration to discharge with intra-muscular ketamine, versus 80 minutes with IV).

Dose

Dissociation can usually be achieved with:

1-1.5mg/kg iv (given over 1-2 mins to avoid apnoea); top up dose of 0.5mg/kg iv can be given if required

4mg/kg im, a repeat dose of 2-4mg/kg can be given after 10 minutes if sedation inadequate

Note – Several studies have shown that higher ketamine doses are required for smaller children

It is normally good practice to site a cannula when the child is dissociated if using the IM route, in case the procedure takes longer or any other drugs are required, and in order to titrate any top-up doses more accurately.

During the procedure

Talk gently and tell the child to choose a dream as they drift off to sleep. You can also describe (or get the parent to describe) a pleasant scene as you are administering the drug.

Adequate sedation is usually indicated by a lack of response to verbal stimuli and nystagmus.Be patient. The effects of ketamine are usually apparent 1-2 minutes after an intravenous dose, and 5 minutes after an intramuscular dose (this can seem a long time with the orthopaedic surgeon staring at you!) Top-up doses can be given as above, but ensure you have waited sufficient time before topping up.

Atropine 0.02mg/kg up to a maximum of 0.6mg can be used to reduce the hypersalivation caused by ketamine which can lead to larynogospasm or aspiration. Recent studies have shown no benefit to routine co-administration of atropine, though prophylactic administration may be considered in procedures in which minimising oral secretions is important, such as lip or tongue wounds. It is worth having it drawn up to be administered in the event of concerns surrounding hypersalivation during the procedure.

Midazolam has previously been used for emergence phenomena, but it should be noted that unpleasant reactions are uncommon and there is no benefit from the routine prophylactic administration of midazolam in children. There is significant variation in the literature with regards to dose, ranging from 0.02mg/kg to 0.1mg/kg. I favour a dose of 0.05mg/kg, but this can be repeated if necessary. I normally don’t draw this up, but have the dose required in my head and the vial nearby should unpleasant reactions arise.

Ondansetron 0.15mg/kg would be the drug of choice for the vomiting child; some clinicians opt to give it prophylactically although there is minimal evidence to support routine use.

After the procedure

Ensure to put the lights down, talk in whispers, and leave the child to wake up

Regular observations are required post procedure until the child is fully awake

Prior to discharge

Ensure the child is fully awake and give them something to eat and drink

Discharge home with parents when able to mobilise and verbalise

Ensure to give appropriate post-procedure advice

References

https://emupdates.com/2011/01/27/taming-the-ketamine-tiger/

https://www.rch.org.au/clinicalguide/guideline_index/Ketamine_use_in_the_emergency_department/

CEM4880-CEC-Guideline-for-Ketamine-sedation-of-children-in-EDs-July-2010-Rev-1.pdf

https://www.rcemlearning.co.uk/references/ketamine-sedation-in-children/

Sedation for transport

Cite this article as:
Andrew Tagg. Sedation for transport, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.8397

One of your colleagues, Andy, has been lucky enough to grab a ticket to a prestigious international conference to be held in Dublin. He is thinking about taking his children but wonders how to keep them happy on the long international flight. He wonders if you have any tricks up your sleeve for keeping children calm during transit.

PAC Conference 2015 – Morris on the difficult adolescent patient

Cite this article as:
Davis, T. PAC Conference 2015 – Morris on the difficult adolescent patient, Don't Forget the Bubbles, 2016. Available at:
https://dontforgetthebubbles.com/pac-conference-2015-morris-on-the-difficult-adolescent-patient/

We have teamed up with APLS to share the videos from their Paediatric Acute Care Conferences. These videos have never been open access before, so if you weren’t able to attend the conferences, then now’s your chance to catch up.

The PAC Conference is run each year by APLS and consists of presentations on a range of topics relevant to paediatric acute and critical care.

PAC conference: Babl on acute care research updates

Cite this article as:
Lawton, B. PAC conference: Babl on acute care research updates, Don't Forget the Bubbles, 2015. Available at:
https://dontforgetthebubbles.com/pac-conference-babl-on-acute-care-research-updates/

The DFTB team are really excited to announce an upcoming video series…We have teamed up with APLS to share the videos from their Paediatric Acute Care Conferences. These videos have never been open access before, so if you weren’t able to attend the conferences, then now’s your chance to catch up.

The PAC Conference is run each year by APLS and consists of presentations on a range of topics relevant to paediatric acute and critical care.