We share education with our paediatric unit once every 5 weeks or so. It’s a great way to learn, to break down barriers, work towards improving the system, share clinical models and understand that we all have the patient’s best interests at heart. We rely heavily on the Royal Children’s Hospital Melbourne guidelines as a common reference point. But people often come from other systems and have different ideas or opinions and this becomes an interesting problem that is worth talking about – especially around the time of trainee change overs. For example some people come from a system where aminophylline isn’t given for critical asthma and look lost when people ask why it hasn’t been prescribed (I have been guilty of this). It is though important at the outset to realise that guidelines very often enhance safety – especially in high risk environments like the ED where a high number of junior doctors work. They help doctors with little experience in a condition, regardless of background, to start on the right clinical track and are a commendable. But it is also important to acknowledge that medicine remains an art and an apprenticeship and there are often many ways of managing a single condition that change from decade to decade and place to place.
Guidelines are only guidelines – they must be well referenced, unbiased and up to date if they are to enable clinicians to understand them and have confidence in them. So how do I know if I should ignore that guideline but adhere to others? And how do I teach that to the registrars? Who will guide me through the guidelines?
As always it comes back to quality education, especially at a local level. As an example lets talk about DKA and Cerebral oedema. This is my attempt to have good local education.
We recently had a paediatric education session where we were reviewing a DKA case. It was a moderate acidosis and it was managed pretty well. DKA is one condition that lends itself well to a guideline and can have death as a side effect if mismanaged. We were talking about why the insulin dose was decreased to 0.05 Units/kg/hr rather than the dextrose infusion being increased. Then somebody who has worked in another Australian system brought up delaying the insulin infusion until fluids had commenced for 1 hour. All of this was during an interdepartmental conversation about trying to prevent rapid falls in glucose (which actually might be unimportant – see below).
Delaying the insulin infusion????? But that’s not in the Royal Childrens Hospital Melbourne Guideline! Surely I have to stop those cells starving and metabolising fat to acids stat! I had no idea that people thought in such a way (and nor did anyone else in our RCH centric world). Is the sky still blue?
So what’s the deal??
Well actually when you look at the Children’s Hospital at Westmead, on their DKA guideline front page summary box, this very concept of delaying insulin is written. Its even in bold type “Do not start insulin before at least one hour of fluid resuscitation”. The Auckland Starship Children’s Hospital has as one of its key points in its DKA guideline: “Insulin infusion to start at 1 hour after initial fluids”. And the International Society for Paediatric and Adolescent Diabetes has it as one of their statements. I can find fewer guidelines that don’t mention it. None of the guidelines reference the statement though and it takes a bit of work to find out that it comes from a paper published in 2006 and the concept is all about trying to prevent that rare but life threatening DKA complication – Cerebral Oedema.
In 2006 Edge et al in a paper titled The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in Children Diabetologia 2006 asked paediatricians (243 participated from 231 hospitals) in the UK to report all cerebral oedema cases and death prospectively for a 3 year period. They identified 43 patients with cerebral oedema out of 2940 reported cases of paediatric DKA. The definition for cerebral oedema was a decrease in consciousness plus one further sign of increased ICP (HT+bradycardia, breathing pattern abnormality, pupillary abnormality, squint, blurred optic disc margins, resp arrest, decerebrate, decorticate or +ve post mortem). They took 169 patients from the other 2940 DKA patients as DKA controls to try and match the severity of the DKA in those with the cerebral oedema. They found that in 50% of the study group no insulin was administered in the first hour of and that if it was, the Odds Ratio for cerebral oedema was 4.7 (p<0.007). They also thought that higher doses of insulin in the second hour might contribute to cerebral oedema but this was not statistically significant. Very strangely they don’t quote insulin doses in Units/kg but rather just total insulin dose over a time frame.
So there you go. That’s the basis for the guidelines.
There might be some physiological merit to the concept – early insulin might increase electrolyte and fluid shifts at the same time you are adding fluid to the vascular system and suddenly perfusing the brain better possibly with some vasogenic induced injury (one theory of cerebral oedema in addition to the cytotoxic mechanisms). It might stimulate the Na/H+ exchanger in cerebral cells allowing sodium (and water) into the cells causing oedema1.
But I can’t get past the fact they didn’t adjust for body weight with regard to both insulin dose and fluid volumes, decreasing its credibility in paediatrics. Which paediatrician doesn’t talk in a weight based way? – that is a big confounder for the rest of the study’s conclusions2 although does not necessarily influence the no insulin in the first hour concept. And even though the cerebral oedema cases were identified as they occurred, the controls and data collection were all retrospective in nature.
Would that change your practice?? Here is a link to the article as full text.
Some other notes about cerebral oedema: Nobody knows how it happens but we definitely know that there are some risk factors and the biggest one is the severity of the DKA. Here are some further points about associations with cerebral oedema:
In a similar 2 studies from Canada3 and the United states4 as well as the UK Edge study,
– between 4.9% and 19% of patients had Cerebral Oedema before therapy was instituted.
– Worse acidosis, higher presenting glucose and higher urea are risk factors for cerebral oedema.
– There appears to be an association with smaller increases in Na with cerebral oedema (ie the sodium should go up with therapy – I imagine this as keeping the corrected sodium stable during therapy – ie the uncorrected sodium goes up as the glucose falls. This make sense to me and I like it.
– There is conflicting data relating to degree of hypocapnia being an independent risk factor.
– There is no evidence to support the association with volume of fluid therapy.
– There was no association between the rate of change of glucose (!)
– In the Edge study, all patients received normal saline in the first hour. (This is a safe fluid)
In 2 older studies Duck5 1988 and Rosenbloom6 1990 found that cerebral oedema was associated with
– Younger age
– New onset of diabetes
But these studies did not have controls included and the more recent controlled studies above did not find these risk factors to be significant.
What else is important? There is evidence that guideline use in DKA results in a low complication rate. A paper published in Paediatrics7 records a 0.5% cerebral oedema rate in 3712 DKA admissions with only one death resulting from sickle cell disease. Of note the Victorian Coroner in 2004 and 2005 published recommendations that DKA be managed according to guidelines after deaths related to DKA cerebral oedema where there was departure from guideline therapy.
So whats my take? As long as you stick to normal saline early on and stick to a safe guideline, regardless of the intricacies of each one, you will treat your patients well. I also think its important to be able recognise cerebral oedema and know to give the 0.5g/kg of mannitol ASAP as soon as the clinical diagnosis is made. And its healthy to know there is more than one guideline out there.
- Edge JA, Jakes RW, Roy Y, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia. 2006;49:2002-2009.
- Hom J, Sinert R. Is fluid therapy associated with cerebral edema in children with diabetic ketoacidosis? Annals of Emergency Medicine 2008 52:1 69-75.
- Lawrence SE, Cummings EA, Gaboury I, et al. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr. 2005;146:688-692.
- Glaser N, Barnett P, McClaslin 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;344:264-269.
- Duck SC, Wyatt DT. Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 1988;113:10-4.
- Rosenbloom A. Intracerebral crises during treatment of diabetic ketoacidosis. Diabetes Care 1990;13:22-33.
- White PC, Dickson BA. Low morbidity and mortality in children with diabetic ketoacidosis treated with isotonic fluids. J Paediatrics 2013 163(3): 761-6.