Diabetic Ketoacidosis

Cite this article as:
Dani Hall. Diabetic Ketoacidosis, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22689

Maisie is 2 years old. Apart from a few coughs and colds, she is usually a very well, happy little girl. She’s been a bit poorly for the last 48 hours – a bit off colour, off her food, lethargic and just not her usual cheeky self.

She’s been drinking though and has had good wet nappies. In triage she has a runny nose and slight cough. She is pretty tachycardic and tachypnoeic and doesn’t look well and so she’s moved to majors.

Maisie is put on a monitor and immediately you can see that her respiratory rate is elevated at 40 breaths per minute with saturations of 97% in air. Her heart rate is also elevated at 150 beats per minute with a normal blood pressure of 105/65. Her capillary refill time is 3 seconds peripherally and she is afebrile.

Her heart sounds are normal, her chest is clear and her abdomen is soft although mildly tender throughout.

The only objective thing you have is the tachypnoea with a bit of a runny nose. You wonder if she has viral induced wheeze and is just too tight for the wheeze to be audible so you prescribe salbutamol and review after 10 minutes. But that’s made no difference to her respiratory rate, and her chest is still completely clear.

Things just don’t add up. She’s holding her tummy – perhaps her tachypnoea and tachycardia are secondary to pain. Her abdomen remains soft with no guarding, but she doesn’t like you palpating it. Could this be appendicitis? Or even worse an intussusception? You speak to the paediatric surgeon who asks you to cannulate Maisie and send some blood. They’ll be down to review her shortly.

You cannulate Maisie and take a venous gas. The results seem to take an age. And your heart sinks when you see them…

She’s acidotic at 7.15 and it looks metabolic with a bicarbonate of 13.9 and base deficit of minus 8.7. Her lactate is 2.9 and her glucose is very high at 29.5. You run a drop of Maisie’s blood through the bedside ketone monitor. Her blood beta-hydroxybutyrate is. 5.1.

This is diabetic ketoacidosis.

DKA can be really difficult to diagnose in toddlers

Classically children with DKA present with polyuria and polydipsia with abdominal pain, nausea, and vomiting. This can progress to dehydration, weakness, and in severe cases, they may be lethargic. Blood tests show a raised white cell count as a physiological response to the raised stress hormones, cortisol and catecholamines, and so are not a reliable indicator of infection. But, and this is a big but, an infection can precipitate DKA so it is important it is considered.

Although ketoacidosis may result in a classic ‘pear drop/acetone’ smell to the breath, not everyone has the chemoreceptors to detect it.

Common misdiagnoses include dehydration secondary to infection or respiratory presentations. Ketoacids stimulate the respiratory centre resulting in rapid fast breathing – Kussmaul breathing – blowing off carbon dioxide to compensate for the metabolic acidosis. It may also present as an acute abdomen as abdominal pain and ileus can result from hypokalaemia, acidosis, and poor gut perfusion. If opioids are given for pain this can suppress the Kussmaul breathing leading to worsening acidosis

 

The BSPED (2020), and ISPAD definitions of DKA are:

acidotic with a bicarbonate of <15 mmol/l or a pH <7.3 and ketones of >3.0 mmol per litre

 

However… just when you starting thinking it was easy… children with known diabetes may develop DKA with normal glucose and so you must keep a high index of suspicion and check pH and ketones in an unwell child with diabetes.

Lack of insulin leads to rising blood glucose levels in the bloodstream. However, this glucose is not transported into the cells and so the body needs to produce an alternative energy source for cellular activity. Three processes occur:

  • muscle is broken down to mobilise amino acids which are then used to create glucose (catabolism)
  • fat is broken down to produce glycol and ketones (lipolysis)
  • the liver uses lactate, glycol and amino acids to create more glucose (gluconeogenesis)

High ketone levels lead to metabolic acidosis.

Hyperglycaemia leads to glucose spilling into the urine (glycosuria). These glucose molecules exert an osmotic pull, dragging water, cations, and anions such as phosphate, potassium, and sodium into the urine (osmotic diuresis). The child becomes dehydrated with physiologically low levels of potassium and phosphate. Ketones also spill into the urine (ketonuria) in preference to chloride, which is retained in the plasma, leading to a worsening chloride-driven acidosis.

Maisie is dehydrated because of the osmotic diuresis exerted by the glucose in her urine. And she’s acidotic because of the ketones circulating in her bloodstream. The question is, what are we going to do about this?

The complications of DKA have incredibly high mortality and morbidity, so we’re going to start here.

 

Cerebral oedema

Cerebral oedema occurs in approximately 1% of children with DKA. While relatively rare, it can have devastating consequences with mortality of approximately 25%. In fact, more than half of all diabetes-related deaths in children are caused by cerebral injury.

Cerebral oedema usually occurs within the first four to 12 hours of starting treatment for DKA, suggesting that it’s the treatment itself that precipitates cerebral oedema.

Risk factors for cerebral oedema in DKA can be split into two groups.

The first group is characterised by children who have a longer duration of symptoms and are therefore more severely dehydrated at presentation. Younger children, particularly toddlers, and children who present in DKA without a previous diagnosis of diabetes mellitus, fall into this group, most likely because they have been in DKA for a long period of time before the diagnosis is made.

The second group is children who develop cerebral oedema because of the treatment they have received. Giving insulin within the first hour of treatment increases the risk of cerebral oedema – the theory is that the usually inactive sodium-hydrogen ion exchange pump is activated by the double hit of high intracellular hydrogen ions early in treatment while children are more acidotic plus insulin crossing the leaky blood-brain-barrier. The exchange pump transports sodium into the intracellular fluid, which then drags water with it due to its osmotic effect, leading to cerebral oedema.

Giving bicarbonate also increases the risk of cerebral oedema. The physiological mechanism of this is unclear but there is some thought that giving bicarbonate to correct acidosis can worsen tissue hypoxia due to effects on 2,3-DPG in erythrocytes (remember acidosis shifts the oxygen dissociation curve to the right, increasing the affinity of haemoglobin and oxygen) or that giving bicarbonate may lead to preferential movement of carbon dioxide across the blood-brain barrier, both of which will promote acidosis and poor oxygen offload in the CSF. However, whatever the cause, it is clear from a systematic review published in 2011 by Chua et al that giving bicarbonate to children with DKA is linked with increased rates of cerebral oedema. The guidance, therefore, mandates that bicarbonate should not be used routinely to correct acidosis. Fluids and insulin will do that by improving skin perfusion and reducing ketosis. Only give bicarbonate if the acidosis is resulting in reduced cardiac function, and then give very carefully…

So, with that in mind, how are we going to treat Maisie?

 

ABC resuscitation

The initial management of a child with DKA follows the principles laid out in APLS: ABC resuscitation.

If a child is obtunded and not protecting their own airway then they should be intubated because of the risk of airway obstruction. However, intubation in DKA is risky… both sedation and the resultant hypercarbia can cause cerebral herniation. Central lines are also risky in these children because of the increased risk of thrombosis. Only use them if absolutely necessary and remove them as soon as possible.

Luckily, Maisie is maintaining her own airway, her GCS is 15 and she is not obtunded. The airway is not a problem for her.

After managing the airway and breathing we move onto circulation. So the question is: should we give Maisie a fluid bolus?

This is a big question.  We are taught that children with cardiovascular compromise should receive fluid boluses to support their circulation.  But assessing cardiovascular compromise in children with DKA can be very challenging. Clinical evaluation of hydration and shock is very difficult in children with DKA. Acidosis drives tachycardia and reduces peripheral skin perfusion.

Koves et al set out to look at this by studying a group of 37 children under 18 presenting with DKA.

Emergency Department doctors recorded heart rate, respiratory rate, blood pressure, cool peripheries, capillary refill time, skin turgor, the presence or absence of sunken eyes and dry mucous membranes to provide a clinical estimate of dehydration. A second emergency department doctor, blinded to the clinical interpretations of the primary doctor, was asked to review the patient before treatment and record their assessment of the same clinical variables. There was a good clinical correlation between the two assessments. Following admission, the children’s weights were measured daily until discharge and percentage dehydration was calculated from the weight gain from admission to discharge.

There was no agreement between assessed and measured dehydration. There was a tendency to overestimate dehydration in children with <6% measured dehydration and underestimate in children >6% dehydrated.

It’s a tricky business and these same parameters clearly won’t be of use in estimating shock in these children.

A true assessment of shock in DKA should rely on assessment on blood pressure measurements and peripheral pulse volume. So that doesn’t really help us. Maisie’s blood pressure and pulse volumes are normal so she’s not shocked. But she clearly is dehydrated. 

BSPED (2020) uses pH and bicarbonate to classify the severity of DKA:

  • pH 7.2–7.29 or bicarbonate <15 mmol/l is mild DKA with 5% dehydration
  • pH 7.1–7.19 or bicarbonate <10 mmol/l is moderate DKA with 7% dehydration
  • pH < 7.1 or bicarbonate <5 mmol/l is severe DKA with 10% dehydration

 

So, are we going to give her a fluid bolus?  Let’s turn to the guidelines…

 

BSPED 2020 states:

Any child in DKA presenting with shock (as per the APLS definition of tachycardia and prolonged capillary refill time) should receive a 20 ml/kg bolus of 0.9% saline over 15 minutes. Let’s call this a ‘resuscitation bolus’.

Further 10 ml/kg boluses may be given if required up to a total of 40 ml/kg. Then add inotropes if the child remains shocked.

Boluses given to treat shock should NOT be subtracted from the calculated fluid deficit.

All children with DKA, whether mild, moderate or severe, who require IV fluids should receive an initial 10 ml/kg bolus over 60 minutes. Let’s call this a ‘rehydration bolus’. This bolus SHOULD be subtracted from the calculated fluid deficit.

 

The American Academy of Pediatrics, agrees that all children with DKA should have a bolus of 10ml/kg over 30 minutes to an hour. If a child is critically unwell with hypovolaemic shock, then additional boluses of 20ml/kg of 0.9% saline should be given.

Australian guidelines vary depending on region – from no routine fluid boluses to 10-20 ml/kg 0.9% saline for the sickest. Some say subtract fluid boluses from rehydration calculations, others don’t. There is no clear consensus.

So why is there so much international variation?

Traditionally, we have been warned about the danger of causing cerebral oedema in children with DKA by giving them too much fluid, reducing serum osmolality and literally flooding the brain. This is based, on the most part, by an old paper that showed an association between large volume fluid resuscitation in DKA and cerebral oedema. Note the word association, not causation.

 

Fluid management in DKA

Dogma has been to restrict fluids in paediatric DKA. It is widely thought that the rapid administration of intravenous fluids reduces serum osmolality, resulting in cerebral oedema. Guidelines traditionally have, therefore, advised slow fluid replacement using isotonic fluids as using hypotonic fluids was thought to cause further drops in osmolality. 

And the evidence seemed to support this.  Retrospective reviews showed better outcomes in children with DKA who received less fluid.

But…

  • only an association had been demonstrated, not causality.
  • and it is reasonable to suspect a confounder in that those with more severe DKA could be expected to be both at higher risk of cerebral oedema and more likely to receive large volumes of fluid resuscitation based on their clinical presentation.

And then along came this paper by Kupperman et al published in the New England Journal of Medicine in 2018, which has shifted thinking a bit, as well as causing some controversy…

Lead authors Nate Kupperman and Nicole Glaser suggested the causal effect of fluid resuscitation and cerebral oedema was a myth in Glaser’s 2001 retrospective case-control study that gave us the list of risk factors for cerebral oedema in DKA.

Kupperman’s team wanted to look specifically at the relationship between fluids and cerebral oedema (defined in the study as a drop in GCS, or longer-term evidence of neurological injury defined as a drop in IQ or short-term memory difficulties 2-6 months later) in DKA in children. They looked at 1255 children with DKA presenting to 13 hospitals in the States over a 9 year period, which, because 101 children presented twice, equated to 1389 episodes of DKA. Children were excluded if their GCS was less than 12, or if they had already received significant DKA management prior to assessment. 289 were withdrawn by the treating physician. The mean age was 11. It’s important to think about all of this as these exclusion criteria mean that the very sick and the very young, two groups who are at significantly increased risk of cerebral oedema, were probably lost in this cohort.

Children were randomized into 4 groups. All patients in both groups received IV insulin at 0.1u/kg/hr. Dextrose was added to the saline solution when blood glucose dropped to 11.1 to 16.7 mmol/l.

 

Children were randomized into 4 groups:

  • FAST rehydration with 0.45% sodium chloride
  • FAST rehydration with 0.9% sodium chloride
  • SLOW rehydration with 0.45% sodium chloride
  • SLOW rehydration with 0.9% sodium chloride

In short, Kupperman’s team found no difference between the groups. There was no significant difference in GCS, or longer-term evidence of neurological injury. The endpoint that many of us are most concerned about, clinically apparent brain injury (deterioration in neurological status requiring hyperosmolar therapy or endotracheal intubation or resulting in death) was a secondary outcome, presumably due to its rarity and hence difficulty in showing statistically significant differences between groups. But again, there was no significant difference between groups.

There was a 0.9% rate of brain injury overall and it didn’t matter which type of fluids or how fast. Patients were more likely to get hyperchloraemic acidosis in the 0.9% NaCl group but this is of debatable clinical significance.

The evidence does not seem to support our traditionally cautious approach to DKA. The speed of IV fluids does not seem to be the cause of brain injury in DKA. But… and this is a big but… don’t forget the youngest and sickest patients weren’t included. All we can probably really conclude is that children who are not in the at-risk group for cerebral oedema are probably more resilient to higher volumes of fluids delivered at faster rates.

Ok… back to Maisie. How are we going to manage her fluids

 

Well, again it depends where in the world Maisie presents. 

 

BSPED 2020 advises to calculate maintenance fluids the same way as they’re normally calculated for children in the UK:

  • 100 ml/kg/day for the first 10kg
  • plus 50ml/kg/day for each kg between 10 and 20kg
  • plus 20ml/kg/day for each kg above 20kg

(A maximum weight of 80kg should be used for fluid calculations)

 

The International Society for Pediatric and Adolescent Diabetes guidance is as follows:

ISPAD says

  • Shock is rare in DKA but if present should be treated with 20ml/kg fluid boluses, repeated as necessary to achieve tissue perfusion.
  • Give all children a 10ml/kg bolus over an hour to rehydrate them.
  • Calculate maintenance fluids in the normal way using the simplified Holliday-Segar formula.
  • Replace rehydration fluids over 24-48 hours, using clinical signs of dehydration to estimate the degree of dehydration. 2 or 3 signs would constitute to 5% dehydration, more signs would equate to 7% dehydration and weak pulses, hypotension or oliguria would indicate the child is 10% dehydrated.

Managing electrolytes

Once you’ve navigated the quagmire of fluid management in DKA, you need to think about adding electrolytes. Remember, glucose molecules in the urine exert an osmotic pull, dragging water, cations, and anions such as phosphate, potassium, and sodium into the urine: the child becomes dehydrated with physiologically low levels of the electrolytes potassium and phosphate.

Always assume whole body potassium depletion in DKA. This is compounded by the treatment you give which causes potassium to move intracellularly. Replace potassium as soon as the patient has urine outpatient and labs confirm the child is not hyperkalaemic.

An ECG will give you clues about clinically significant hypokalaemia:

  • Prominent U waves (an extra positive deflection at the end of the T wave)
  • Flat or biphasic T waves
  • ST-segment depression
  • Prolonged PR interval

Although phosphate is lost in the urine as part of the osmotic diuresis in DKA, prospective studies involving relatively small numbers of subjects and with limited statistical power have not shown clinical benefit from phosphate replacement. Administrating phosphate can be dangerous, by causing calcium levels to drop. However, symptomatic severe hypophosphataemia, when serum phosphate levels drop below 1 mg/dL with an ensuing metabolic encephalopathy or depressed cardiorespiratory function, can be dangerous, albeit very rare. A sensible approach is to monitor phosphate levels alongside regular potassium level checks and, if a child is hypophosphataemic and symptomatic, replace phosphate whilst carefully monitoring serum calcium levels.

Back to Maisie. We’ve managed her fluids according to our local guidelines. But how can we tell if we’ve got the balance right?

We can’t monitor urine output as Maisie is going to be polyuric anyway because of the osmotic effect of glycosuria. Her capillary refill time will be prolonged because she’s acidotic and therefore skin perfusion will be reduced.

And her serum sodium and osmolality won’t be reliable indicators of fluid balance because of the effect of plasma glucose on her electrolytes. On top of this, her kidneys will preferentially excrete chloride from any saline and potassium chloride over ketones so there’s limited value to monitoring the anion gap because it doesn’t differentiate between hyperchloraemia or ketones. Instead, we should measure Maisie’s corrected sodium.

Because of its osmotic effect, glucose drags water with it into the intravascular compartment diluting the other osmols – 1mmol rise in glucose will drop sodium and chloride by 1mmol/L.  If Maisie’s glucose goes up by 1 the other osmols will go down by 1.  If glucose goes down by 1 the other osmols will go up by 1.

The corrected sodium must rise with therapy at a rate of 0.5-1 mmol/h

  • Falling corrected sodium means too much water gain: we’ve been overzealous the fluids.
  • A rapidly rising corrected sodium means too much water loss: we’ve been too fluid restrictive.

The Evelina London South Thames Retrieval Service has a great corrected sodium calculator on their website. You plug in her numbers – her initial sodium was 148 with glucose of 29.5, giving her a corrected sodium of 157.6. A couple of hours have passed and her latest gas shows that her glucose has come down to 24.5 – great – and her sodium has improved slightly to 144. You press calculate…

… and your heart sinks as you see her second corrected sodium has fallen by 6 points to 151.6 as you know that the corrected sodium must rise with treatment.

You go back to Maisie’s bedside to review her.

Maisie has dropped her GCS to 12 (E3, V4, M5).  This is incredibly worrying – her GCS was 15 when you last checked on her.  You move her round to resus and ask your nurse to grab some hypertonic saline.

 

Clinical features of cerebral oedema

  • Headache
  • Slowing heart rate
  • Rising blood pressure
  • Focal neurology such as cranial nerve palsies
  • Falling oxygen saturations
  • Change in neurological status including restlessness, irritability, drowsiness, confusion, incontinence

Treat cerebral oedema with either hypertonic saline or mannitol.

Calculate your dose of hypertonic saline or mannitol before you need it and know where it’s kept. If a child has an acute deterioration, treat it.

Mannitol is an osmotic diuretic and can be given at 0.5 – 1 g/kg over 10-15 minutes. The effects should be apparent after 15 minutes. Mannitol lasts about 2 hours and can be repeated at this point if needed.

Hypertonic saline is a good alternative to mannitol or can be used after mannitol if a second agent is needed.

Don’t forget other neuroprotective measures like elevating the head of the bed to 30 degrees and intubation if concern regarding airway protection.

If there’s no improvement in GCS, do a CT, but not until the child is stable. CT is used to identify any potential lesion that would warrant neurosurgery – intracranial haemorrhage, or a lesion that would warrant anticoagulation such as thrombosis.

Hypertonic saline or mannitol?

DeCourcey et al (2013) conducted a retrospective cohort study over a 10 year period to see whether the increase in the use of hypertonic saline had had any effect on mortality in DKA. They looked at over 43,000 children under the age of 19 with DKA presenting to 41 children’s hospitals in America and found that the use of hypertonic saline replaced mannitol as the most commonly used agent in many of the participating hospitals. Controversially, their data suggested that hypertonic saline may not have benefits over mannitol and may be associated with a higher mortality rate.

However, this does remain controversial, with a counter-argument published as a letter to the editor a few months later arguing that (1) the fact that mortality from cerebral oedema in DKA had decreased by 83% over the same time period that use of hypertonic saline had increased, along with (2) the fact that DeCourcey’s paper only found a statistically significant difference in mortality between hypertonic saline and mannitol once age and race were removed from analyses (two factors that, themselves, have a significant influence on mortality in DKA-related cerebral oedema), meant that we shouldn’t be rushing to conclude that hypertonic saline is less safe than mannitol in the treatment of cerebral oedema.

No guidelines are yet to recommend mannitol over hypertonic saline. This seems to be one of those situations where a prospective study is needed to really answer the question of whether mannitol is superior, or at least non-inferior to hypertonic saline.

 

Back to Maisie. You give Maisie 3ml / kg 3% saline over 15 minutes and are relieved to see her wake up.  You decrease her fluid prescription and thankfully from that point on her corrected sodium starts to slowly rise.

 

Insulin

Finally, you’re ready to give Maisie some insulin. Insulin will control Maisie’s glucose and switch off ketosis, therefore improving her acidosis.  Some departments use 0.1 units/kg/hr and some use 0.05 units/kg/hr.  The question is, what is the optimal dose? 

Nasllasamy’s team set out to compare the efficacy and safety of low-dose and standard-dose insulin infusions. They randomized 50 children under the age of 13 with DKA presenting over a 12 month period to receive insulin infused at either 0.05 units/kg/hr or 0.1 units/kg/h. They found that the rate of decrease in blood glucose and time to resolution of acidosis were similar in each group. There was no statistical difference in complication rates of hypokalaemia, hypoglycaemia or cerebral oedema.

This study suggests that low dose insulin is non-inferior to standard-dose insulin in managing children with DKA.  It’s important to note that this was a non-inferiority trial and a larger study, powered to show superiority would be helpful. However, many units have been using lower doses of insulin at 0.05 units/kg/hr safely for some time and this study supports the use of lower dose insulin.

BSPED 2020 states:

Insulin can be given at 0.05units/kg/hr or 0.1 units/kg/hr, although ‘0.05 units/kg/hr would probably be sufficient in most cases except perhaps severe DKA’.

Children under 5 years should be given 0.05 units/kg/hr.

And so, as Maisie is young and therefore in the higher risk group of children with DKA, you opt to start her on insulin at 0.05 units/kg/hr.

In children who are already on long-acting insulin, BSPED 2020 states that it should be continued, or if they are newly diagnosed, they advise to consider starting long-acting subcutaneous insulin alongside intravenous insulin.<

Manage high-risk children in PICU

  • pH <7.1
  • young (under 2s or under 5s depending which guideline you read)
  • cardiovascular shock
  • corrected sodium >150 or <130
  • hyper or hypokalaemia
  • altered conscious state
  • glucose >50

Maisie has multiple risk factors: she’s young and she developed clinically apparent cerebral oedema.  You admit her to PICU where she makes stable progress and is discharged home 4 days later on a subcutaneous insulin regime.

Selected references

Take a read of Chris Gray’s take for St Emlyns here

Lawrence SE, Cummings EA, Gaboury I, Daneman D. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr 2005; 146:688

Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med 2001; 344:264

Edge JA, Jakes RW, Roy Y, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006; 49:2002

Marcin JP, Glaser N, Barnett P, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002; 141:793

Scibilia J, Finegold D, Dorman J, et al. Why do children with diabetes die? Acta Endocrinol Suppl (Copenh) 1986; 279:326

Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child 2001; 85:16

Chua HR, Schneider A and Bellomo R. Bicarbonate in diabetic ketoacidosis – a systematic review. Ann Intensive Care. 2011; 1:23

Koves IH et al. The Accuracy of Clinical Assessment of Dehydration During Diabetic Ketoacidosis in Childhood. Diabetes Care 2004:27(10);2485-2487

Kuppermann N et al. Clinical Trial of Fluid Infusion Rates  for Pediatric Diabetic Ketoacidosis. N Engl J Med. 2018;378:2275-87

DeCourcey et al. Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral edema in pediatric diabetic ketoacidosis: an 11-year retrospective analysis of mortality. Pediatr Crit Care Med. 2013; 14(7):694-700

Tasker RC, Burns J. Hypertonic saline therapy for cerebral edema in diabetic ketoacidosis: no change yet, please. Pediatr Crit Care Med. 2014;15(3):284-285

Nallasamy K et al. Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis. A Randomized Clinical Trial. JAMA Pediatr. 2014; 168(11): 999 – 1005

ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidodis and the hyperglycaemic hyperosmlar state. Pediatric Diabetes 2018; 19 (Suppl. 27): 155–177

PERN – Global Research: Stuart Dalziel at DFTB19

Cite this article as:
Team DFTB. PERN – Global Research: Stuart Dalziel at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.21852

Stuart Dalziel is a professor of paediatric emergency medicine in Tāmaki-makau-rau (Auckland), the director of research at Starship Hospital. He is a past chair of PREDICT and current chair of PERN. It is in this role that he spoke at DFTB19.

Practice made perfect?

Cite this article as:
Sonia Twigg. Practice made perfect?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20694

Okay, perhaps  not perfect but we think these bite sized chunks of simulation from Children’s Health Queensland are pretty good! They are free to download and play with. You can find access to all current OPTIMUS resources here. Enjoy!

 

Introducing BONUS – A Bank of Independently Useful Sims

 

 

 

What are they?

OPTIMUS BONUS is an ongoing project driven by Children’s Health Queensland involving the creation of simulation education packages on topics in paediatric resuscitation.  Each package contains;

  • An introduction by an expert explaining why the topic is important.
  • A simulation with clear learning objectives, instructions and hints for debriefing.
  • Pre-reading resources for participants. These are fun and easy to read resources including podcasts, videos, guidelines and apps.
  • An infographic summarising the topic. QR codes on the posters link to Just In Time Training resources including videos and guidelines.  Just point the camera on your smart phone at the poster and a link will appear to the website to see the video.

 

Who writes them?

The STORK team (Simulation Training Optimising Resuscitation in Kids) from Children’s Health Queensland provides simulation based education throughout Queensland.  We provide two courses as part of our OPTIMUS curriculum; Optimus CORE (for first responders) and Optimus PRIME (for mid phase care while awaiting retrieval).

 

 Why did we make them?

 

What we love about them

  • They’re free to download, expert reviewed, repeatedly tested and assessed by a statewide advisory group to ensure we’re providing a quality product.
  • Our infographics look awesome, summarise the key messages, are easy to share on social media and easy to store on your phone.
  • Some packages contain Just in Time Training JITT resources and videos via QR codes to give you the info you need when you need it :
    • Just scan the QR codes on your phone to see refresher videos before you go and perform that skill
  • We’ve curated great open access #FOAMed resources on paediatric topics for each Simulation, so you can deep dive into more learning before or after the Sim!

 

Love the simulations and want to help out?

Thanks!  We need your help to share these simulations and infographics online any way you can. Shout out to @childhealthqld @LankyTwig @Caroelearning @paedsem and @symon_ben on twitter if you’re using them!

The other thing that REALLY helps is getting good feedback.  So, if you have thoughts on them to share fill out the surveys via the QR codes in the package so we can keep making better simulations to share with the world.

If you’d like to know more, email us at stork@health.qld.gov.au

Other than that, retweet them, share them widely, and help us improve paediatric care everywhere in the world.

 

Enjoy!

Sonia and the BONUS team

Dr Sonia Twigg (@LankyTwig), Dr Benjamin Symon (@symon_ben), Dr Carolina Ardino Sarmiento (@caroelearning), Dr Ben Lawton (@paedsem) Ms Louise Dodson and Mrs Tricia Pilotto.

 

Selected references

Case, Nicky, “How to remember anything forever-ish.:  Oct 2018.  Available at: https://ncase.me/remember/

Cheng et al, “Resuscitation Education Science: Educational Strategies to Improve Outcomes from Cardiac Arrest; A Scientific Statement from the American Heart Association.”Circulation 2018; 138: e82-e122. Available at: https://www.ahajournals.org/doi/10.1161/CIR.0000000000000583

Cheng et al, “Highlights from the 2018 AHA Statement on Resuscitation.” June 2018.  Available at: https://canadiem.org/aha-scientific-statement-on-resuscitation-education/

Dubner S.“Freakonomics Radio.  How to become great at just about anything (Ep 244).” Apr 2016.  Available at: https://freakonomics.com/podcast/peak/

Ericsson A,“Peak” Vintage 2017.

Top 5 papers in PEM – Bubble Wrap live: Arj Rao at DFTB18

Cite this article as:
Team DFTB. Top 5 papers in PEM – Bubble Wrap live: Arj Rao at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20392

The Bubble Wrap is our monthly round up of some of the interesting papers that have made it to press. It’s impossible to keep up to date with every publication that comes out but at least you might be a little bit wiser.

Top 5 Papers in PEM

Cite this article as:
Tessa Davis. Top 5 Papers in PEM, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.18476

This post is based on a talk I presented at the RCEM Spring Conference in April 2019 – Top 5 papers in PEM.

Kylie and Jason are enjoying their time at home with their first baby. The highs of being new parents is at its peak and true sleep deprivation is yet to set in. Jayden is two weeks old and is simply perfect. They spend hours staring at him each day marvelling at the perfect human they have created. 

As we follow Jayden through his journey to adulthood, we’ll encounter some common paediatric problems. The 5.5 papers I have chosen were selected because: they cover common presentations; they use large patients groups; and they were conducted by well-respected and highly regarded research groups. But back to our story…

 One night Jayden seems a bit more unsettled than normal. When they check his temperature it’s 38.4. They get in the car and bring Jayden to ED

 Febrile neonates are a huge source of concern – we know that they can deteriorate quickly and we usually err on the side of caution by doing a full septic screen, IV antibiotics, and admission. Actually many of these babies don’t have a serious bacterial infection. Is there a way to tell which ones do?

When you see Jayden in your ED, you ask yourself is…should I do a full septic screen?

Paper 1 - Kupperman et al, 2019, A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections, JAMA Pediatrics

This paper aimed to derive and validate a highly accurate prediction rule to identify infant at low risk of SBI. The patients were febrile infants 60 days and younger (who had a rectal temp of >38 in the ED or a fever at home within the preceding 24 hours)

They excluded those who were critically ill, who had antibiotics in the preceding 48 hours, those born premature, and those with other medical conditions.

There were 1821 febrile infants included.

The authors considered clinical suspicion of SBI. They then look at various markers: blood culture; urine culture and urinalysis; CSF; FBC; and procalcitonin levels. The outcomes  considered were serious bacterial infection – that is bacterial meningitis, bacteraemia, or urinary tract infection.

Overall, the rates of SBI in this group was 9%. The authors formulated a rule with a very high sensitivity (97.7%) for identifying those at low risk of serious bacterial infection. They were low risk if they fulfilled three criteria:

  • negative urinalysis
  • neutrophil count of less than 4/mm3 
  • procalcitonin of less than 0.5ng/ml

61.3% of their patient group were low risk.

Interestingly their low risk rule does not include use of  lumbar puncture67.4% of the low risk group had a lumbar puncture that would not have been necessary.

Key take away: There may be some febrile neonates that are low risk, and therefore we could avoid a lumbar puncture and full work up. In practical terms, this is unlikely to change our practice at the moment. Many of us cannot send a procalcitonin in the ED, and we might have to wait several hours to get a neutrophil count back. However this does bode well for the future in identifying which of these well febrile neonates are low risk.

Jayden does get a full septic screen. He has IV antibiotics for 48 hours and remains well. His blood cultures are negative so his antibiotics are stopped and he is discharged.

FLASH FORWARD…

 

 

Jayden is growing well. At 7 months of age, he is looking great and developmentally normal. Dad, Jason, smokes, but reassures you that he never does so in the house. Jayden develops a cough and two days later starts breathing very quickly and noisily. They head to the emergency department.

Jayden has bronchiolitis. This is very common and your departments and wards have no doubt been filled with these children over the winter. We know that little works with these children. So you force yourself to hold back the ‘trial of salbutamol’ because it won’t make any difference.. But high flow does seem to be the one thing (along with oxygen) that might make a difference.

You ask yourself the question...should I start high flow?

Paper 2 - Franklin et al, A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis. NEJM. 2018. 378(12):1121-1131

This study looks at infants under 12 months old with a clinical diagnosis of bronchiolitis and a need for supplemental oxygen. 1472 were included (after exclusions). Patients were excluded if: they had an alternative diagnosis; they had cyanotic heart disease; or they were on home oxygen.

Patients were randomised to either high flow or low flow. The high flow group were given heated humidified high flow oxygen – 2L/kg/min via Optiflow. The oxygen was then weaned to achieve target saturations, and they were taken off high flow once they had been on air for four hours. The low flow group were given wall oxygen via nasal cannulae at 2L/min max.

The outcome  was escalation of care. This meant who in the low flow group was escalated to high flow, and who in the high flow group was escalated to BiPAP or was intubated. Treatment failure was based on: an increase in heart rate; if the respiratory rate increased or didn’t drop; if they were needing oxygen in >2L/min of flow or >0.4 FiO2 to maintain their saturations; or if they achieve a high early warning score. Clinicians could also escalate care themselves (34% were escalated in this way).

Escalation of care occurred much more commonly in the low flow group – with 12% being escalated in the high flow group and 23% in the low flow group.

 

Interestingly there was no difference in the length of stay between the two groups.

Key take away: High flow does reduce the need for escalation. Escalation itself is significant – it requires increased nursing attention for low flow patients while they are transferred onto Optiflow.  There may be less medical staffing on the wards if the child deteriorates on high flow overnight. Although they aren’t comparing like with like, escalation itself is an important clinical event. They also demonstrated that high flow does not increase the number of adverse events (for example there was no difference in the number of pneumothoraces between the groups). High flow is safe to use and we should consider starting it early in ED.

You start Jayden on high flow in ED and he stabilises. 12 hours later he is weaned off on the ward and is discharged the following day.

FLASH FORWARD…

Jayden is now a healthy 3 year old boy. He loves Paw Patrol.  He hates vegetables and won’t eat any food that is the colour green or yellow. Kylie and Jason are expecting their next child, and Jason has finally quit smoking. Unfortunately Jayden is prone to wheezy episodes and now has his very own inhaler which he hates using. The change in weather in London, from quite cold to…colder, seems to have triggered something and he’s now pretty wheezy and short of breath. They head into their favourite emergency department.

 Jayden is now firmly in the realm of viral-induced wheeze. Yes, it’s all on a spectrum, but he’s now 3 years old with an inhaler. You asses him and think he should have a salbutamol burst.

As you are writing the salbutamol up, your SHO asks  you – should I give him steroids?

Paper 3 - Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2018 Jan 17.

 This paper aimed to assess the efficacy of oral prednisolone in children presenting to an ED with viral wheeze.

The patients included were 2-6 years old. They were excluded if: saturations were less than 92% in air; they had a silent chest; they had sepsis; there was a previous PICU admission for wheeze; they had prematurity; or they had recently had steroids.

605 patients were included and they were randomised to receive either prednisolone or placebo. The prednisolone group received 1mg/kg prednisolone once a day for three days. The placebo group received a placebo medication (matched for volume and taste to prednisolone) once a day for three days.

Patients were assessed for their wheeze severity using a validated pulmonary score.

The outcome measures were length of stay (until clinically fit for discharge). They also considered re-attendance, readmission, salbutamol usage, and residual symptoms.

The results are tricky to interpret. Those who were discharged from ED within four hours did not benefit from prednisolone. However there may be some benefit in the mild to moderate wheeze group, and some in those who used salbutamol at home prior to presenting to ED. Interestingly this paper did not support our previously held belief that those children with atopy respond better to prednisolone.

 Key take homes: Some pre-schoolers are steroid responsive, but identifying which ones is a challenge. As Damian Roland discusses here, it is likely that we are seeing lots of children presenting with the same symptoms (wheeze) but with different pathology behind it. Once we can identify the pathology we can start to target specific groups of patients with management that works.

You decided not to give Jayden prednisolone and after his salbutamol burst he stretches to 4 hours and is discharged home.

FLASH FORWARD…

Jayden is 5 years old and in his excitement of building the new Hogwarts Lego castle he accidentally swallows a Lego head. Kylie and Jason aren’t sure whether to worry or not? So they take him into ED.

Children ingesting random objects is a common presentation to ED.

When you see Jayden in the department, his parents ask you…should I search through his poo?

Paper 3.5 - Tagg, A. , Roland, D. , Leo, G. S.Y., Knight, K. , Goldstein, H. , Davis, T. , DFTB, (2018), Everything is awesome: Don’t forget the Lego. J Paediatr Child Health. doi:10.1111/jpc.14309

Myself and 5 of my fearless, and brave, paediatric colleagues swallowed a Lego head each to see how quickly it passed. The paper was generously published in the Journal of Paediatrics and Child Health.

To ensure serious scientific rigour, we put together some scoring systems.

The Stool Hardness and Transit time (the SHAT score) took into account how hard our stools were, and whether that impacted (no pun intended) on the time to retrieve the Lego head.

And out main outcome was the Found And Retrieved Time (the FART score). This was the time to get our Lego heads back, and the average FART score was 1.71 days.

Unfortunately one of the six of us didn’t find his Lego head. After valiantly searching through his own faeces for two weeks, he gave up. And it may still be up there.

Key take home: Don’t search through poo, it’s gross.

Jayden heads home happily to finish building his Lego Castle.

FLASH FORWARD.

Jayden is 6 years old. He thinks Paw Patrol is for losers. Fortunately he still loves Lego and Harry Potter. He also enjoys climbing. Unfortunately, two days ago he fell off the ladder coming down from his bunk bed. He seemed okay at the time, and Kylie and Jason had other plans that evening, so they decided to keep him at home. Now, two days later, he has a massive egg on his head and has been complaining of a headache. He also vomited yesterday. They bring him to ED.

 

We have fabulous head injury guidance for kids thanks to PECARN, CHALICE, and CATCH. But actually PECARN and CATCH specifically exclude injuries more than 24 hours old, and CHALICE doesn’t publish data on this group. So, for Jayden you need to put the NICE guideline away because it doesn’t apply. This is a common grey area.

The question you ask is….should I scan his head?

Paper 4 - Borland M, Dalziel SR, Phillips N, Lyttle M, Bressan S, Oakley E, Hearps SJC, Kochar A, Furyk J, Cheek J, Neutze J, Gilhotra Y, Dalton S, Babl F. Delayed Presentations to Emergency Departments of Children With Head Injury: A PREDICT Study, Annals of Emergency Medicine, DOI: https://doi.org/10.1016/j.annemergmed.2018.11.035

This paper aimed to establish the prevalence of traumatic brain injuries in children presenting more than 24 hours after the head injury.

Traumatic brain injury (TBI) was defined as: intracranial haemorrhage; contusion; cerebral oedema; diffuse axonal injury; traumatic infarction; shearing injury; or a sigmoid sinus thrombosis.

The also looked a clinically significant traumatic brain injury (cTBI) – this included death, intubation for more than 24 hours, neurosurgery, or admission for 2 or more nights to hospital.

The patients were from the Australian Paediatric Head Injury Study Cohort which was 20,137 patients. 5% of these presented over 24 hours after the injury. 981 children were included in this study.

The authors considered the injury characteristics and demographics, trying to find an association between mechanism and delay in presentation. Those presenting were more likely to have: a non-frontal scalp haematoma; headache; vomiting; and assault with NAI concern. Those with loss of consciousness and amnesia were more likely to have presented within the first 24 hours.

The CT rates were much higher in the late presentation group – 20.6% being scanned in the delayed group and only 7.9% in the early group. This probably reflects the lack of evidence in this area, and therefore we feel safer doing more scans.

But the rates of TBI also varied. 3.8% in the delayed presentation group had a TBI, whereas only 1.2% in the early presentation group did.

The rates cTBI were the same between the groups at 0.8%

Key take homes: There is an increased risk of TBI when presenting more than 24 hours after a head injury injury. The authors found that risk is increased if the patient has a non-frontal scalp haematoma or a suspicion of a depressed skull fracture.

You decide to scan Jayden’s head, but it turns out to be normal and he is discharged home.

FLASH FORWARD… 

Jayden is 8. He’s been drinking a LOT of water over the last few weeks and seems to be weeing constantly. His clothes seem a bit big for him too. He looks so bad one day (and has vomiting and abdominal pain) that Jason finally reneges and takes him into ED.

Jayden has DKA. The debate about over-zealous fluid administrations and its relationship to the dreaded cerebral oedema is long-standing. Previous research suggested a link but only by association, not causality.

You ask yourself…how fast should I give IV fluids?

Paper 5 - Kupperman et al. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis NEJM 2018 vol 378 (24) pp 2275-2287

The study examines the causal effect between fluid resuscitation and cerebral oedema.

They included 1389 episodes of DKA. Exclusions were mainly due to too much management prior to contact with the study team, as well as children with a GCS<12. The median age was 11. It should be noted that the very young and the very sick are probably lost in this cohort.

Patients were randomised to received either fast or slow rehydration, and then were split again into received either 0.9% NaCl or 0.45% NaCl.

The fast rehydration group received 20ml/kg bolus and then replacement of 10% deficit, half over 12 hours and rest over next 24 hours. The slow rehydration group received a 10ml/kg bolus and then replacement of 5% deficit over 48 hours. Maintenance fluids and insulin were given in addition.

The outcomes looked at were deterioration of neurological status within first 24 hours of treatment. They also assessed short term memory during treatment, and IQ 2-6 months after the episode of DKA.

In short, they found no difference between the groups. There was a 0.9% rate of brain injury overall and it didn’t matter which type of fluids or how fast. Patients were more likely to get hyperchloraemic acidosis in the 0.9% NaCl group but this is of debatable clinical significance.

Key take homes: The evidence does not support our traditionally cautious approach to DKA. The speed of IV fluids does not seem to be the cause of brain injury in DKA.

You resuscitate Jayden and send him off to the ward. He is discharged a few days later with good support from the Endocrine team for management of his diabetes.

FLASH FORWARD…

Jayden is now 16 years old and next time he comes to ED, he’ll be in the harsh world of Adult ED. We have navigated him through his common childhood presentations to ED and answered the key questions we ask ourselves every day in the Paeds ED.

 

Should I do a full septic screen on this hot baby?

Should I start high flow on this infant with bronchiolitis?

Should I give prednisolone to this 2 year old with wheeze?

Should I scan this child with a head injury?

How fast should I give fluids to my DKA?

And most importantly, do I ever need to sift through my child’s poo, or my own ever again?

Sweet and Salty – fluids in DKA

Cite this article as:
Ben Lawton. Sweet and Salty – fluids in DKA, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.16130

During our training in paediatric emergency medicine most of us will have been cautioned repeatedly of the dangers of over-zealous fluid administration in children with diabetic ketoacidosis. Cerebral oedema is the feared complication of this disease process and, as traditional wisdom would have it, either rapid fluid administration or the use of any hypotonic IV fluid would invite this situation upon your poor unsuspecting patient.