Prepare for transport: Costas Kanaris at DFTB19

Cite this article as:
Team DFTB. Prepare for transport: Costas Kanaris at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22605

Costas Kanaris is a paediatric intensivist working in Manchester. He is also internet-famous for his challenging #fridayquiz in which he presents a case, drip-feeding information, as the Twitter audience figure out the diagnosis and the best way to treat the patient in front of them.

This time he tries it in front of a live studio audience. Here is a teaser to tickle your brain.

 

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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Surviving Sepsis Campaign International Guidelines

Cite this article as:
Damian Roland. Surviving Sepsis Campaign International Guidelines, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.23460

The lens with which you view sepsis is dependent on the environment and emotion in which you associate the term. For a parent, this may be the spectrum from having never heard the term before “Your child is well enough to go home, we’ve ruled out sepsis and other serious conditions” to the anguish of being told, “I’m afraid your child died of sepsis“. This spectrum remains equally wide for health care professionals. A family doctor or general practitioner may never see a case of confirmed sepsis, and an emergency clinician can potentially go years between seeing a truly shocked child. An intensivist, however, may deal with the consequences on a weekly basis. Even in the last month, we have seen two papers from the same publishing group; one highlighting the global burden of sepsis and the other challenging the current hype surrounding its recognition and management.

Regardless of your viewpoint, the publication of the Surviving Sepsis campaign’s international guidance will have been of interest.

 

Weiss, S.L., Peters, M.J., Alhazzani, W. et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med 46, 10–67 (2020). https://doi.org/10.1007/s00134-019-05878-6

 

It is important to recognize two features of this publication which should carry an important health warning in its interpretation.

The first is that the authors are clear that they are focusing on severe sepsis or septic shock. While in adult practice definitions have changed, these have not been formalized or ratified for children:

 

“For the purposes of these guidelines, we define septic shock in children as severe infection leading to cardiovascular dysfunction (including hypotension, need for treatment with a vasoactive medication, or impaired perfusion) and “sepsis-associated organ dysfunction” in children as severe infection leading to cardiovascular and/or non-cardiovascular organ dysfunction.”

 

The authors clearly recognize that the absence of a clear definition of paediatric sepsis is challenging health care providers and organizations. The group has steered away from suggesting management options in the ‘pre-sepsis’ group i.e. those children with potential infections that may result in sepsis and have physiological instability but without organ dysfunction. They suggest that management practices for this group aren’t radically different, however:

 

Even though these guidelines are not intended to address the management of infection with or without SIRS when there is not associated acute organ dysfunction, we recognize that sepsis exists as a spectrum and some children without known acute organ dysfunction may still benefit from similar therapies as those with known organ dysfunction

 

The second is that this is a consensus document. It is neither a systematic review nor a clinical practice guideline (in a local hospital sense). It comprises the opinions of an expert group of clinicians (49 in fact) from a variety of international settings using the best available evidence. The publication is essentially a list of recommendations. This approach is valid in situations where evidence may be heterogeneous and that randomized controlled trials can not be performed for all possible permutations of clinical practice. As with all things in science, however robust the data is, it still needs interpreting and that interpretation is subject to all manner of explicit and implicit bias.

 

The panel supports that these guidelines should constitute a general scheme of “best practice,” but that translation to treatment algorithms or bundles and standards of care will need to account for variation in the availability of local healthcare resources.

 

Without becoming meta it’s important that this blog itself needs a health warning. It’s an interpretation of an interpretation of evidence.

So the big-ticket items

1. A child was defined as beyond 37 weeks gestation and up to 18 years old.

2. They apply to children with severe sepsis or septic shock as defined by the 2005 International Pediatric Sepsis Consensus Conference or inclusive of severe infection leading to life-threatening organ dysfunction.

2005 definition:

  • greater than or equal to two age-based systemic inflammatory response syndrome (SIRS) criteria
  • confirmed or suspected invasive infection, and cardiovascular dysfunction
  • acute respiratory distress syndrome (ARDS), or greater than or equal to two non-cardiovascular organ system dysfunctions

Septic shock was defined as the subset with cardiovascular dysfunction, which included hypotension, treatment with a vasoactive medication, or impaired perfusion.

3. Panel members were selected through recommendations from chairs and vice-chairs of the 12 worldwide member organizations. Each panel member was required to be a practicing healthcare professional with a focus on the acute and/or emergent care of critically ill children with septic shock or other sepsis-associated acute organ dysfunction. There was lay representation and the final membership was felt to be demographically diverse with regard to sex, race, and geography.

4. The panel was assisted by various methodological experts and split into six groups

  • recognition and management of infection
  • hemodynamics and resuscitation
  • ventilation
  • endocrine and metabolic therapies
  • adjunctive therapies
  • review research priorities in pediatric sepsis

5. A list of critical questions was developed in the PICO format (Population, Intervention, Control, and Outcome) which was then rigorously searched for by a specialist medical librarian and the resulting literature assessed according to GRADE criteria a well-recognized methodology for systemically presenting summaries of evidence.

6. Following discussion and debate recommendations would be made:

 

We classified recommendations as strong or weak using the language “We recommend…” or “We suggest…” respectively. We judged a strong recommendation in favor of an intervention to have desirable effects of adherence that will clearly outweigh the undesirable effects. We judged a weak recommendation in favor of an intervention to have desirable consequences of adherence that will probably outweigh the undesirable consequences, but confidence is diminished either because the quality of evidence was low or the benefits and risks were closely balanced.

 

The paper goes into considerable detail (which is why it is 55 pages long) into the rationale behind the recommendations. They are all summarised in the appendix (commencing page e102). It is beyond the scope of this blog to explore all the recommendations in detail, and it is important that health care providers read the paper itself. The following highlights some of the areas which may prompt debate or query.

 

‘Screening’ remains in

For those in emergency and acute care, this recommendation may have come as a surprise given a large amount of anecdotal feedback and experience suggesting that current screening mechanisms for the un-differentiated child are neither specific nor sensitive. It is worth nothing again the panel was looking at severe sepsis or shock and the evidence for ‘bundles’ of care i.e. targeted or mandated treatments once recognized is relatively robust. There is a further section on protocols/guidelines for treatment but it may have been useful to separate the afferent limb (recognition) from the efferent limb (response) in relation to collated evidence. This is important as the evidence for ‘bundles’ is cited under screening, with minimal evidence of screening approaches alone put forward (or to be fair to the panel perhaps of insufficient quality to make a judgment on).

Although subtle I think the panel recognized how important local buy-in is in relation to quality improvement. Of note, there is nothing on national guidance for recognizing sepsis. They also highlight how blindly integrating screening with any other scoring system may not be as beneficial as believed.

Ultimately no one particular screening system is recommended.

 

There is no target lactate

There appears to be a palpable sense of regret that the evidence didn’t support any particular threshold for lactate. Despite evidence of rising mortality with increasing lactate, the panel was not able to determine a specific level.

However, no RCTs have tested whether initial or serial measurement of blood lactate directly informs evaluation and/or management in children. Lactate levels should, therefore, be interpreted as a part of a more comprehensive assessment of clinical status and perfusion.

 

Take blood cultures but don’t delay treatment to obtain them

Appreciating this isn’t a particularly scientific response, but well, duh.

 

One hour time to treatment for those in shock but up to three hours without it. 

This is the potential game-changer from this body of work. While the evidence shows a temporal relationship between the administration of antibiotics and outcome in severe sepsis some pooled data demonstrated that it was unlikely the hour alone made the difference. Given the numerous papers showing a linear relationship between time to administration and outcome the ‘golden hour” was maintained. In the absence of shock, the panel felt, based on data showing a three-hour threshold effect, this would be a reasonable time point. This will be a welcome relief for those working in areas where there are associated penalties for not reaching the hour window and hopefully will remove some of the gaming associated with this target.

 

Broad spectrums antibiotics, but narrow when pathogens available

Little controversy here. The panel highlight that 48 hours should be the maximum time that is allowed to pass before re-evaluation in the absence of culture growth rather than a standard time to elapse.

If no pathogen is identified, we recommend narrowing or stopping empiric antimicrobial therapy according to clinical presentation, site of infection, host risk factors, and adequacy of clinical improvement in discussion with infectious disease and/or microbiological expert advice.

There are a number of recommendations on immunocompromised children and source control which appear pragmatic.

 

Bolus if intensive care available, if not then don’t unless documented hypotension

In units with access to intensive care, 40-60ml/kg bolus fluid (10-20ml/kg per bolus) over the first hour is recommended. With no intensive care, and in the absence of hypotension, then avoiding bolus and just commencing maintenance is recommended. It is not clear how long access to intensive care has to be to switch from fluid liberal to restrictive.

**Post-publication note (13/02/20): A more correct description of no intensive care would be “in health systems with no access to intensive care”. The guidance states, “For children with septic shock without signs of fluid overload in low-resource settings where advanced supportive and intensive care is not available, the panel recommends against bolus fluid administration,”. This question is raised in the comments section below as for units in without intensive care on site but it will resourced health systems then ‘access’ to intensive care should be assumed**

For purposes of this weak recommendation, hypotension can be defined as:

 

The panel suggests crystalloids, rather than albumin, and balanced/buffered crystalloids rather than 0.9% saline. They recommend against using starches or gelatin.

 

Use advanced haemodynamic variables, not bedside clinical signs in isolation

The evidence didn’t support a target mean arterial blood pressure but suggested avoiding using clinical signs to differentiate into cold and warm shock. No one monitoring approach was advised but included cardiac output, cardiac index, systemic vascular resistance, and central venous oxygen saturation.

 

Intensive care vasoactive and ventilation management is given but acknowledged as weak recommendations 

There is a list of suggestions regarding vasoactive infusion and ventilatory strategies that are very specific to intensive care management. While a number of recommendations are given (epinephrine rather than dopamine for septic shock for example) these are generally based on the panels summation of weak evidence.

There are further suggestions on corticosteroid management, nutrition, and blood products which will be of interest to those in intensive care and anaesthetic settings.

 

Summary

This is a very rich piece of work that is well structured and easy to read (even if you are not an expert on a particular field of practice). For most paediatricians there is unlikely to be an immediate change in practice but the softening of antibiotic time to delivery in the non-shocked child and emphasis of local review of sepsis incidence and performance will be welcome. How these filter into national guidance will be determined country by country but it is unlikely that radically different views can be drawn from the available evidence. What is still sorely needed is a working definition for the non-hypotensive child with sepsis (or an acknowledgment that perhaps this isn’t really a clinical entity…)

 

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

The curious incident of the wheeze in the night time

Cite this article as:
Costas Kanaris. The curious incident of the wheeze in the night time, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.22330

The first rule of the DFTBquiz is that the approach to each particular case and patient is not dogma, nor is it the only way in which the case can be safely managed in our virtual ED. There are numerous ways to approach critical illness. As long as the applied clinical treatment passes both the evidenced based medicine and family litmus then we have nothing to fear apart from the disease process itself.

So how would the DFTB team at Bubbles Central Hospital approach the child with life threatening bronchospasm, altered sensorium that has a pneumothorax and an SVT?

If you missed the original question – check it out here

This has been the second most successful #pedsicu f#ridayquiz to date with >30k impressions and answers from 29 different countries! It was a complex case of common pathologies amalgamated in one patient – status asthmaticus with a pneumothorax and SVT.

We outline the DFTB team’s take on the case and how we would approach it if we had this patient in our own resus bay. Please note this is not the only way to approach the patient but rather what our consensus is as to how to prioritize clinical issues and minimize risk in this patient by using a rational, evidence-based and pharmacologically prudent approach.  There were numerous excellent answers from across the globe. Here are a few highlights…

Things to consider are:

  • What is immediately the most life-threatening pathology? The pneumothorax? The SVT? The severe bronchospasm?
  • Why does the child have lactic acidosis?
  • Is it really an SVT or is it a tachycardia, exacerbated by nebulized beta-agonists? What risks are posed by any intervention we undertake?
  • How do we minimize the risks identified above?
  • What drugs should we use for intubation and what how do we maintain anaesthesia thereafter?

1. What is immediately the most life-threatening pathology? 

It is clear that this child is at high risk of cardiorespiratory arrest if we do nothing.

Clues to that are hypoxia, hypercarbia (especially in the context of altered sensorium)[1]; air trapping to the extent where a pneumothorax has developed (a known complication of asthma)[2] and the lactic acidosis, which in this case is likely to be secondary to a combination SVT leading to myocardial hypoperfusion and the respiratory muscles tiring (more on that later).

On the ABCDEFG approach (Airway, Breathing, Circulation, Disability, Exposure, Fluids, Glucose) we are taught to approach airway first. This failsafe approach may work well in most clinical emergencies but in this case, intubating before achieving cardiorespiratory stability is likely to put the patient in an even stickier situation.  Breathing (i.e. adequate oxygenation) is likely to be the first pathology to lead to cardiorespiratory arrest. That needs to be addressed first. The SVT is likely to cause considerable instability during intubation; this is superimposed to the pre-existing high risk of adverse events that accompany life-threatening asthma[3]. So the SVT needs to be cardioverted prior to intubation if possible.

Furthermore, the risk of converting a pneumothorax to a full-blown tension pneumothorax by attempting to intubate first is significant. Most modified RSI methods include a bag and mask ventilation technique. The application of positive pressure ventilation either before or after the ETT is in place –once the patient is established on a ventilator- risks changing the nature of the pneumothorax from a simple one to a life-threatening tension-type one[4].

In this case, therefore, airway stabilization – although high on the list of priorities – should come after we have optimized breathing and circulation (unless the patient arrests beforehand).


2. Why does the child have lactic acidosis?

The latter is important to understand and differentiate in someone who has been receiving a beta-agonist.

In the context of asthma lactic acidosis may be due to overproduction and/or inadequate clearance of lactic acid. Therefore, lactic acidosis in a child with severe bronchospasm could result:-

      • if patients were in occult shock
      • if produced by tiring respiratory muscles (i.e., respiratory muscle oxygen demand outstripping oxygen supply)
      • if produced by the lung parenchyma
      • if changes in glycolysis were caused by beta-agonist administration.
      • lactic acid could also be under metabolized by the liver

In our case the patient did not receive any IV salbutamol and only a couple of nebulizers; pharmacogenic lactic acidosis is therefore unlikely.

Much more likely is a lactic acidosis as a result of tiring respiratory and cardiac muscles. The latter is especially important to recognize in the context of an SVT. The myocardium perfuses during diastole[6]. If the HR is 300, the diastolic time is minimal, so there isn’t much time for the myocardium to be adequately perfused.

Tired respiratory and cardiac muscles make for a very high-risk intubation process.


3. Is it really an SVT or is it a tachycardia, exacerbated by nebulized beta-agonists?

It is tempting to think that such a significant tachycardia has been caused by a combination of factors: the patient is hypovolaemic, the patient is stressed, we gave him a couple of salbutamol nebs – and so on.

How can we differentiate a sinus tachycardia from an SVT?

Most textbooks will empirically state if the HR is >210-220 then the rhythm’s is more likely to be SVT, if it is <200-210 then it is likely to be sinus tachycardia.

This is loosely true but not always, especially in the context of paediatrics where we have different HR norms for each age.

Beat-to-beat variability is important in differentiating SVT from sinus tachycardia. Whilst in SVT each (P) QRST complex looks the same as the one after it, in sinus tachycardia each PQRST complex is different. A 12 lead ECG will help you ascertain this more accurately.

The presence of P waves is another determining factor.  A true SVT oughtn’t to have P waves preceding the QRS complex, whereas in a sinus tachycardia a P wave is usually present.  This is often tricky to differentiate in practice, especially if the ECG or cardiac monitors are tuned onto real-time speed. The best trick to apply is to slow the monitors down enough. This will slow down the speed of the PQRST complexes, allowing us to better visualize the P wave.

Vagal manoeuvers and pharmacological therapy if there is uncertainty about the cardiac rhythm is poor practice and should be avoided.  Cardiac output equals stroke volume times heart rate (CO= SVxHR). If we try to slow down the heart in the context of very fast sinus tachycardia with drugs or by stimulating the vagus nerve we will drop the cardiac output and put the patient at risk of a cardiac arrest.  We always need to be sure of the rhythm before any intervention.

If you are still uncertain, a reasonably safe bedside test would be to give 10ml/kg fluid bolus (ideally balanced solution) and keep an eye on the monitor whilst it’s infusing. If it is an SVT the HR will not budge. If it is sinus tachycardia, you are much more likely to see some slowing down of the rate.


4. What risks are posed by any intervention we undertake?

The risks of intubating someone with pneumothorax have been outlined above.

PPV can change a stable, small pneumothorax into a life-threatening tension pneumothorax. This dictates that we should ideally put a temporary chest drain in to decompress the thorax prior to intubation.

The other risk in optimizing breathing in this scenario is an exacerbation of the SVT by giving IV bronchodilating agents that are known to have a potent chronotropic effect. Both aminophylline [7] and salbutamol [8] are known to be chronotropic, but evidence would suggest that aminophylline causes less of a chronotropic effect than salbutamol[9]. With that in mind, loading with IV aminophylline in order to break the bronchospasm spiral would be the best (or least bad) option.

Also worth noting that MgSO4 is a potent vasodilator, so if we intend to use it in this setting to optimize bronchodilation it needs to be done as a low infusion (over 25-30 minutes)

The risks we may encounter whilst in improving circulation prior to intubation are twofold.

Firstly, in addressing cardioversion, adenosine is the most commonly used agent in treating SVT pharmacologically. A known side effect of adenosine, however, is bronchospasm[10].  There is little high-quality evidence to assess the effects of adenosine on asthmatic airways. What little evidence there is (and the evidence is nearly all from adult subjects) would suggest that adenosine is safe to use in patients with reactive airways[11],[12].

Secondly, this patient is likely to have a degree of dehydration. This degree of tachypnoea and work of breathing increases fluid loss through the respiratory tract. The degree of tachycardia also suggests a hyper-metabolic demand, again suggesting increased fluid consumption. It would, therefore, be prudent to give this patient some volume prior to intubation.  As the patient already has metabolic acidosis,  (ab)normal saline would be a poor choice. The chloride content is likely to increase chloride levels leading to a worsening metabolic acidosis [13], which in turn would worsen myocardial contractility [14],[15]. Balanced solutions (Plasmalyte 148 or Hartmann’s) are by far more physiologically appropriate and unlikely to exacerbate the metabolic acidosis [16],[17] and therefore preferred in this instance.


5. How do we minimize the risks identified above?

We have alluded to a lot of the steps in the analysis above. The main objective is to optimize oxygenation and primum non-nocere.

Bronchodilation prior to intubation is key. In this case, it is reasonable to go “all-out” and load with IV aminophylline, IV Hydrocortisone, IV Magnesium and a triple agent nebulizer (repeat if needed) consisting of salbutamol, ipratropium, and adrenaline (croup dose) to try and minimize air trapping by opening up the airways.

A temporary chest drain is important. This will help with pre-intubation oxygenation and reduce the risk of a peri-intubation tension pneumothorax from developing.

Cardiovascular stabilization is also important prior to intubation. Volume resuscitation prior to intubation is best done with a balanced solution (as outlined above) and –if anaemic- possibly blood as that would help with the overall oxygen-carrying capacity and give the patient more reserve. It is important to remember that this should be done in 10ml/kg aliquots because a high proportion of children with SVT will have concomitant congenital anatomical abnormalities. Give the fluid, assess response, check for rhonchi and hepatomegaly, and repeat as necessary. It is possible that the patient may still need cardiovascular support after intubation.

Which inotrope is best will be dictated by whether or not we have managed to successfully cardiovert (by vagal maneuvers first, by incremental doses of adenosine second and by DC cardioversion third). The inotropes need to be pre-drawn, prior to intubation so that we can start them quickly. This is not a scenario where we should be playing catch-up and preparation is key.

IV adrenaline would be a strong favorite in the usual asthmatic, not least because it has potent bronchodilatory effects and is reasonably safe to use in asthmatics[18]. If we have managed to stop the SVT then there would be a strong argument to favour this.  Adrenaline, of course, is also a potent chronotrope, so we should; on balance avoid it in someone with SVT. Noradrenaline is the least chronotropic out of our inotrope choices, so if we are still in SVT or we think that the patient is at high risk of reverting back into SVT then it would, on balance, be our best choice. Have a low threshold for inserting an IO if you don’t have enough large-bore access.


6. What drugs should we use for intubation and what how do we maintain anaesthesia thereafter?

 There is a long-standing truism in the art of rapid sequence intubation that says, “there is no such thing as a cardiostable induction”. This is especially true in the intubation process of critically ill children. All induction agents tend to vasodilate and cause a blood pressure drop. Couple that with the vagal stimulation caused by the laryngoscope and you can see why RSI is tricky business.

Arguably the least cardio-unstable combination of drugs in this setting would be ketamine  (1-2mg/kg),fentanyl (1mcg/kg), and rocuronium (1-2mg/kg). Ketamine has the added benefit of being a bronchodilator so it would definitely help in reducing the bronchospasm[19].

Intubating using sevoflurane may also be attractive for experienced anesthetists, not least because of the potent bronchodilatory effect that it can offer us[20]. This would still be my second choice however, because of how much vasodilation and blood pressure drop it may cause.

Always be prepared for adverse events during intubation. In this case, our chest drain needs to be in first, we need some inotropes pre-drawn as well as some volume in case the BP drops. A favorite trick of mine is using dilute adrenaline as a bolus to improve BP or HR or both should they drop during intubation.

The dilution is essentially tenfold of the resuscitation dose. Take the resus dose, dilute it with 10 ml of saline and you can bolus the eventual solution in 1ml aliquots. This is a superior drug when compared to commonly used atropine as it addresses also the BP drop and not just the HR drop.

Maintenance of anaesthesia is often with continuous infusion of morphine and midazolam. In this case, those agents would not be the best choice. Morphine is known to increase histamine release and is therefore likely to exacerbate bronchospasm and peripheral vasodilatation.  Fentanyl, as a continuous infusion, is proven to cause less histamine release and is, therefore, a superior choice in this case[21].

Coupling the fentanyl with a ketamine infusion (instead of midazolam) would also be preferable, mainly because of ketamine’s bronchodilatory effects. For doses /rates and dilutions of these pharmacological agents fill in and print the drug chart on crashcall.net or the one provided by your regional paediatric critical care transport team.

 

So what plan would go up on the PED resus board?

  1. Optimize B and C first. Prepare Airway trolley  (including 4, 4.5 and 5 cuffed ETT) and draw up 10ml aliquots of Plasmalyte dilute adrenaline. Draw up noradrenaline and adrenaline for infusions if needed.
  2. Break the bronchospasm cycle. IV aminophylline, slow IV MgSO4, triple neb (adrenaline, salbutamol, ipratropium). Temporary chest drain –and prepare for a more robust one after intubation.
  3. Confirm rhythm. 10ml/kg fluid volume, vagal maneuvers, incrementally increasing doses of adenosine until Cardioversion 100mcg/kgè200mcg/kgè 300mcg/kgè500mcg/kg. If adenosine fails for DC Cardioversion. Ideally prior to intubation.
  4. 1-2mg/kg ketamine, 1mcg/kg fentanyl, 1-2mg/kg Rocuronium; maintain anaesthesia with ketamine and fentanyl infusions (crashcall.net doses/rates)
  5. Empirical cover, include cover for atypical infections: Ceftriaxone + Clarithromycin. If flu possible consider Oseltamivir.
  6. Avoid 0.9%Saline, 10ml/kg aliquot of Plasmalyte or Hartman’s, if anaemic consider blood. Reassess after every bolus (liver size and rales).
  7. Keep an eye, likely to rise (stress response, steroids, salbutamol) unlikely to need treatment even if high.

Remember, this is just the DFTB team’s approach. There are numerous ways to skin a cat; if you have an alternative way we are keen to hear it!

References

[1] Holley, Anthony D., and Robert J. Boots. “management of acute severe and near‐fatal asthma.” Emergency Medicine Australasia 21.4 (2009): 259-268.

[2] Porpodis, Konstantinos, et al. “Pneumothorax and asthma.” Journal of thoracic disease 6.Suppl 1 (2014): S152.

[3] Zimmerman, JANICE L., et al. “Endotracheal intubation and mechanical ventilation in severe asthma.” Critical care medicine 21.11 (1993): 1727-1730.

[4] Bacon, A. K., et al. “Crisis management during anaesthesia: pneumothorax.” BMJ Quality & Safety 14.3 (2005): e18-e18.

[5] Forsythe, Sean M., and Gregory A. Schmidt. “Sodium bicarbonate for the treatment of lactic acidosis.” Chest 117.1 (2000): 260-267.

[6] Heusch, G. “Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents.” British journal of pharmacology 153.8 (2008): 1589-1601.

[7] Urthaler, Ferdinand, and Thomas N. James. “Both direct and neurally mediated components of the chronotropic actions of aminophylline.” Chest 70.1 (1976): 24-32.

[8] Crane, J. et al “Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline.” Thorax 44.2 (1989): 136-140.

[9] Morice, A. H., et al. “A comparison of the ventilatory, cardiovascular and metabolic effects of salbutamol, aminophylline and vasoactive intestinal peptide in normal subjects.” British journal of clinical pharmacology 22.2 (1986): 149-153.

[10] Bennett-Guerrero, Elliott, and Christopher C. Young. “Bronchospasm after intravenous adenosine administration.” Anesthesia & Analgesia 79.2 (1994): 386-388.

[11] Burki, Nausherwan K., Mahmud Alam, and Lu-Yuan Lee. “The pulmonary effects of intravenous adenosine in asthmatic subjects.” Respiratory research 7.1 (2006): 139.

[12] Terry, Polly, and Gail Lumsden. “Using intravenous adenosine in asthmatics.” Emergency Medicine Journal 18.1 (2001): 61-61.

[13] Kellum, John A. “Saline-induced hyperchloremic metabolic acidosis.” Critical care medicine 30.1 (2002): 259-261.

[14] Cingolani, Horacio E., et al. “Depression of human myocardial contractility with “respiratory” and “metabolic” acidosis.” Surgery 77.3 (1975): 427-432.

[15] Williamson, John R., et al. “Effects of acidosis on myocardial contractility and metabolism.” Acta medica scandinavica199.S587 (1976): 95-112.

[16] Bellomo, Rinaldo, et al. “Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.” Jama 308.15 (2012): 1566-1572.

[17] Chowdhury, Abeed H., et al. “A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers.” Annals of surgery 256.1 (2012): 18-24.

[18] Putland, Mark, Debra Kerr, and Anne-Maree Kelly. “Adverse events associated with the use of intravenous epinephrine in emergency department patients presenting with severe asthma.” Annals of emergency medicine 47.6 (2006): 559-563.

[19] Allen, Joseph Y., and Charles G. Macias. “The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma.” Annals of emergency medicine 46.1 (2005): 43-50.

[20] Schutte, D., et al. “Sevoflurane therapy for life-threatening asthma in children.” British journal of anaesthesia 111.6 (2013): 967-970.

[21] Rosow, Carl E., et al. “Histamine release during morphine and fentanyl anesthesia.” Anesthesiology 56.2 (1982): 93-96.

 

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.

What is the evidence for high flow in bronchiolitis?

Cite this article as:
Tessa Davis. What is the evidence for high flow in bronchiolitis?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20191

Over recent years, the use of high flow nasal cannula in the treatment of bronchiolitis in infants has increased. Whilst it used to be mainly used in PICU, it is now widely used in EDs and on the wards. The recent PARIS trial examined whether delaying starting high flow in infants with bronchiolitis led to a worse outcome (it didn’t). See Alasdair Munro’s excellent analysis here.

But is high flow actually useful in these patients, and if so when? Should we be using it in our Emergency Departments at all?

The PREDICT research group published an updated systematic review this month in the Journal of Paediatrics and Child Health.

Anticoagulation in children : Fiona Newall at DFTB18

Cite this article as:
Team DFTB. Anticoagulation in children : Fiona Newall at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20144

Professor Fiona Newall is Director of Nursing Research at the Royal Children’s Hospital in Melbourne and has a special interest in anticoagulation in children. If you think that the only patients in a hospital that need anticoagulation are old people then you should watch this talk from DFTB18.

ConSEPT – the reveal: Stuart Dalziel at DFTB18

Cite this article as:
Team DFTB. ConSEPT – the reveal: Stuart Dalziel at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20055

Given that DFTB18 was held in Melbourne it was important to highlight the work of PREDICT (the Paediatric Research In Emergency Department International Collaborative)* This talk, by Stuart Dalziel, centred around ConSEPT and the management of convulsive status epilepticus.

Fluid assessment in sepsis: Elliot Long at DFTB18

Cite this article as:
Team DFTB. Fluid assessment in sepsis: Elliot Long at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19912

Given that DFTB18 was held in Melbourne it was important to highlight the work of PREDICT (the Paediatric Research In Emergency Department International Collaborative)* This talk, by Elliot Long, centred around his work on the role of fluids in the septic child.

Awakening the FEAST: Why did fluid boluses kill?

Cite this article as:
Alasdair Munro. Awakening the FEAST: Why did fluid boluses kill?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19418

In paediatric medicine, it sometimes feels like we talk about sepsis more than anything else. We’ve all become familiar with the “sepsis bundles”, including a generous portion of intravenous fluid given as a rapid bolus in resuscitation.

This is why the FEAST trial blew everyone’s minds when it was published in 2011. This large RCT in East Africa of over 3000 children was stopped early when it demonstrated an increase in mortality for children given a fluid bolus of either 0.9% saline or 5% albumin instead of just maintenance fluids. It sparked huge controversy and various groups trying to explain away this effect with limited success. Guidelines however were not changed on the basis of this trial, because of concerns that it wasn’t applicable to a high resource setting, because the trial included children without measurement of blood pressure, and partially because no-one could come up with a good explanation for why this would be the case (see this breakdown in The Lancet). Why would giving a fluid bolus increase mortality in sepsis?

This is the question a new paper in The Lancet Respiratory Medicine tries to answer, using data from the FEAST trial (and others), and including members of the original FEAST team.

Levin M, Cunnington A, Wilson C, Nadel S, Lang H, Ninis N et al. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial. Lancet Respir Med. Epub June 2019 https://doi.org/10.1016/S2213-2600(19)30114-6

This study is a little complicated, but we can break it down to make it a bit easier to digest. Let’s start with the most important thing:

Research Question

We want to know why a fluid bolus increased mortality in FEAST.

To get to that, there are 2 questions asked in this study:

  1. Are changes in cardiovascular, neurological or respiratory function, or blood oxygen carrying capacity or biochemistry associated with adverse outcomes in children with sepsis?
  2. In the FEAST trial, were fluid boluses associated with changes in these parameters?

In order to address these 2 questions, the populations analysed were a mix from several studies of childhood sepsis, including:

3170 patients from the FEAST trial (children with sepsis from East Africa)

502 patients from the UK with meningococcal sepsis

448 from Malawi with cerebral malaria

61 children from South Africa with presumed sepsis/gastroenteritis (unpublished)

18,863 children attending a UK emergency department (unpublished)

Outcomes

The authors developed novel physiological scores for cardiovascular, neurological and respiratory function which could be assessed in a low/middle income setting. They didn’t use existing scores, as these are not single organ specific and require monitoring or tests which are not available in these settings, so could not be applied to the FEAST population

The scores were:

The cohorts other than FEAST were essentially just used to test their scoring system. They performed logistic regression to see if an increasing score (i.e. worsening on function) correlated with an “adverse outcome”. Basically testing if their score had any clinical relevance.

In the FEAST population, physiological scores and Hb, lactate, base excess, pH and electrolytes were measured at baseline (prior to any fluids) and then at several time points after fluid administration (either bolus or maintenance). Distributions of these scores were compared in the fluid bolus vs no bolus groups in FEAST to see if this could account for the increased mortality.

Other analyses

To cut a long study short – there are a huge number of different comparative analyses performed in this study. Feel free to spend days wading through the data (I know I will), but for now we’ll stick to the headlines which are the answers to our 2 big questions.

1.    Are changes in cardio, neuro or resp function, or blood oxygen carrying capacity or biochem associated with adverse outcomes?

The answer is yes.

In the FEAST trial, for every 10 units increase (worsening) in score, the odds ratio for death was; respiratory 1.09, neurological 1.26 and cardiovascular 1.09. So they’ve developed a new score, and looks like it tells is what we want.

In the other cohorts analysed, worsening of almost every physiological parameter was also associated with adverse outcomes (see pg 22 supp appendix)

2.    In the FEAST trial, were fluid boluses associated with changes in these parameters?

Yes they were.

Giving a fluid bolus increased (worsened) respiratory score by 3.45 at 1hr and neurological score by 2.64 at 1hr. These differences disappeared at 12h.

Fluid bolus decreased (improved) cardiovascular score by 2.17 at 1h. This difference disappeared at 12h.

Fluid bolus decreased Hb by 0.33g/dL at 8hrs

Fluid bolus did not change lactate

Fluid bolus decreased bicarbonate by 0.96mmol/L and decreased base excess by 1.41mEq/L

Additional points of interest

It made no difference if they received albumin or saline boluses, which is expected as there was no mortality difference either.

Higher volume fluid boluses (≥30mL/kg) were associated with worse respiratory and neurological scores at 4h then lower volume boluses, but high or low volume bolus made no difference in cardiovascular scores.

Significantly, in a post hoc principle component analysis (stay with me – this is not complicated I promise) – differences in physiological scores at 1h explain all the differences in mortality observed between bolus and no-bolus groups of the trial. The major determinants were neurological score, base excess and respiratory score. This is important as although differences between the groups were only apparent at 1h, this was enough to completely account for the differences in mortality.

There is some exciting cluster analysis (1. Mild derangement of scores, 2. Severe anaemia, high lactate and CV score, 3. High resp and neuro scores), but we will ignore this for now as the answer to our main questions didn’t differ among any of the clusters.

So how does a fluid bolus increase mortality in sepsis?

Whilst this question cannot be definitively answered through this study, the authors have presented a bioplausible explanation of their results. They have summarised it in an amazing picture, but if you like bullet points…

A fluid boluses causes:

  1. Haemodilution, causing anaemia, reducing O2 delivery and worsening metabolic acidosis
  2. Hyperchloraemia and bicarbonate dilution, worsening metabolic acidosis
  3. Worsening of respiratory function (partially through increased acidosis), causes decreased CO2 excretion, which both worsens metabolic acidosis and causes cerebral vasodilation, increasing intracranial pressure
  4. Cerebral oedema, causing raised intracranial pressure.

Limitations of the study

Should we all stop giving fluid boluses to children with sepsis now? Some limitations to consider from this study include:

  • This resource limited setting without intensive care may not be directly applicable to high income settings, as mechanical ventilation and neuro intensive care may be able to mitigate some of the adverse effects of bolus
  • Their scores are not independently validated and were not initially derived from the data
  • The influence of large volume fluid boluses may suffer from confounding by indication
  • Acid-base data was only available at 24hrs, by which time most deaths had occurred. Some analysis was performed using imputations.
  • Some of the statistics are almost impenetrable to us mere mortals

Conclusion

In the FEAST trial of children with sepsis in East Africa, a fluid bolus of either 0.9% saline or 5% albumin was associated with a worsening of respiratory and neurological function, anaemia and metabolic acidosis, which in turn was associated with increased mortality. There was a transient increase in cardiovascular function.

The implications of this according to the authors:

Particular care should be taken if considering giving fluid boluses to children with sepsis and respiratory or neurological compromise at presentation

Resuscitation with buffered solutions may be preferable in severely unwell children to avoid worsening of metabolic acidosis (trials in adults currently underway to assess this)

Where next?

As the authors state, it is unlikely ethical approval will be given for further trials of fluid boluses in a low/middle income setting following the increased mortality shown in FEAST. Conversely, trials in higher income countries are difficult because fluid boluses are seen as standard of care for sepsis, and as demonstrated recently in the FISH trial, sepsis has become so rare that trials of fluid management are difficult, even approaching unfeasible. We may find people become generally more cautious when implementing fluid bolus resuscitation as time goes on, perhaps with 10mL/kg boluses becoming preferable to the historically recommended 20mL/kg.

For further reading, check out the great accompanying editorial here, and check out references 3 – 14 in the paper for some of the heated controversy surrounding FEAST.

Vicarious Trauma : It’s ok to not be ok

Cite this article as:
Jasmine Antoine. Vicarious Trauma : It’s ok to not be ok, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.19256

One afternoon my team broke the news to three different families that their children had a non survivable condition. That same week I was involved with a patient transitioning to a palliative pathway focused on comfort. I returned home to utter the words, “She is so sweet, I hope she dies soon.

For many of us, days like these, occur commonly.

Being a doctor is a privilege, an honour, a calling. Our jobs are stressful, diagnostically challenging, involve managing team members, and effectively communicating and engaging with different families whom have different needs. We are reliant on our knowledge and skills. What sets our job apart from other high stress environments is that any given day can involve death and dying. We see distressing conditions. Our day includes the uncommon, the unlucky and the unfortunate events of life. To the public these events occur few and far between, but for us it may be a daily occurrence -a relentless barrage of traumatic events, poor outcomes and sad stories.

The intensive care environment is difficult to navigate. The rates of burnout, mental health issues and self medication are high amongst our peers. 70% of junior doctors feel burnt out following a neonatal rotation. Strikingly, their (our) rates of suicide are twice that of the general population. Most of us have heard the words compassion fatigue. Some of us may even be familiar with vicarious trauma – the negative experience of working directly with traumatised populations. Compassion fatigue and vicarious trauma are on a spectrum. We initially may feel overwhelmed by our interaction but this can develop into symptoms of post traumatic stress.

At DFTB18, I spoke about some of the things we can do to reduce this happening to us, and the events above reinforced that message;

  • Seek the support of those around you.
  • Reflect with your supervisor.
  • Get together with your team to debrief.
  • Seek professional psychological support.
  • Foster a culture in your workplace that is supportive and open, whilst also taking time for yourself.
  • Make a regular appointment to see you GP.

And remember, it’s ok not to be ok

For more on this topic of the difficulties of dealing with death and burn out hit up DFTB at:

Burning out by Mark Garcia

A short story about death by Andy Tagg

Selected References

Boss RD, Geller G, Donohue PK. Conflicts in Learning to Care for Critically Ill Newborns: “It makes me question my own morals”, Bioethical Inquiry. 2015;12:437-448

Hauser N, Natalucci G, Ulrich H, Sabine K, Fauchere JC. Work related burden on physicians and nurses working in neonatal intensive care units: a survey, Journal of Neonatology and Clinical Pediatrics. 2015;2:2:0013.

Nimmo A, Huggard, P. A systematic review of the measurement of compassion fatigue, vicarious trauma and secondary traumatic stress in physicians. Australian Journal of Disaster and Trauma Studies. 2013;1:37-44.

Stress, burnout and vicarious trauma: looking after yourself. RACGP Webinar Series.

Stabbings in adolescents

Cite this article as:
Tessa Davis. Stabbings in adolescents, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.17337

It’s a regular day in your Paeds ED. You’ve just pulled a piece of lego out of a child left nostril; there are two wheezy kids waiting for review to see if they can stretch to two hours; and there is a 2 month old with a rash that you’re currently seeing  – everyone is waiting for you to come up with a clever diagnosis. As you stare at the spots and wait for some inspiration, you hear one of your nursing colleagues call…