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Three Part Question

In [a child with gastroenteritis and dehydration who is unwell has a low random bedside blood sugar measurement] should [an extensive metabolic screen should be performed]as [a metabolic defect is possible (hypoglycaemia)]?

Clinical Scenario

A twenty month old girl is seen on the paediatric assessment unit with a 3 day history of diarrhoea, vomiting, and poor fluid intake. On examination she is miserable and lethargic and moderately dehydrated. A random bedside blood sugar measurement is 2.1 mmol/L. A metabolic screen is performed and results are not suggestive of an underlying metabolic disorder. Before discharge a controlled fast is carried out with no abnormality detected. Was all this investigation necessary?

Search Strategy

Searches were performed in March 2007. Medline from 1950 –to date was used via Dialog Datastar. The Cochrane database revealed no results.
Search terms used were hypoglycaemia, gastroenteritis and diarrhoea. Searches limited to humans and children (0-18) for hypoglycaemia and gastroenteritis, and hypoglycaemia and diarrhoea.

Search Outcome

produced 107 hits. 6 of these hits were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Hirschhorn N, Lindenbaum J, Greenough WB, Mahmood Alam S 1966 Pakistan	693 children <15kg admitted with acute diarrhoeal disease	Retrospective review	Review clinical and biochemical features of hypoglycaemic children with acute diarrhoeal disease	13 of 693 (1.9%) children had hypoglycaemia. 9 had bacterial causes found.	Only comatose children had blood sugar checked in initial study
Glyn-Jones R 1975 South Africa and Rhodesia (now Zimbabwe)	868 children age 2 to 35 months dehydrated as a result of gastroenteritis	Retrospective survey	Investigate the relationship of blood sugar to nutrition, mortality serum sodium	69 of 868 (7.9%) children were hypoglycaemic. 9 of 252 (3.6%) normally nourished children were hypoglycaemic.	Metabolic problems not excluded other than malnutrition. Only included children who had blood sugar measured, these could have been the sickest.
Majid Molla A, Hossain M, Islam R et al 1981 Bangladesh	26 521 children age < 10 years with diarrhoea of different aetiology admitted to the treatment centre	Retrospective study	Demonstrate the significance of hypoglycaemia in terms of mortality.	231 of 26 521 (0.9%) children were hypoglycaemic.	Only 20% of all children with acute gastroenteritis get admitted therefore this represents the sick end of the population. However all 26 521 had serum glucose measured Metabolic problems not excluded
Bennish ML, Azad AK, Rahman O, Phillips RE 1990 Bangladesh	2003 children age < 15 years admitted to treatment centre with acute diarrhoea	Prospective cohort study	Frequency and outcome of hypoglycaemia.	91 of 2003 (4.5%) children were hypoglycaemic 39 (43%) of whom died.	For 4 months all children had glucose measured then for last 4 months only those with altered consciousness. 25 matching controls from same population to try and investigate aetiology of hypoglycaemia
Reid S, McQuillan S, Losek J 2003 USA	184 children age < 5 years with acute gastroenteritis and dehydration with no known disorder predisposing to hypoglycaemia	Prospective cohort study	To differentiate the clinical features of children with hypoglycaemia and gastroenteritis from those with gastroenteritis alone.	62 of 184 (34%) of children were hypoglycaemic	Did not include all eligible patients instead used a convenience sample therefore results do not represent true incidence of hypoglycaemia
Reid S, Losek J 2005 USA	196 children aged one to 57 months with acute gastroenteritis and dehydration with no known disorder predisposing to hypoglycaemia	Retrospective case series	Estimate prevalence of hypoglycaemia among children dehydrated due to acute gastroenteritis	18 of 196 (9%) children were hypoglycaemic	Dehydration was defined as those who received an IV fluid bolus

Comment(s)

Clinically it is difficult to differentiate children with gastroenteritis and hypoglycaemia from those with gastroenteritis alone as the symptoms are very similar; lethargy, nausea, palor and weakness. These studies do not help decide who is most at risk of hypoglycaemia but pragmatically the longer the period of fasting, the higher the frequency of diarrhoea and vomiting and the younger the child the more likely hypoglycaemia becomes. Hypoglycaemia requires specific intervention, different to that for gastroenteritis and if left untreated and unrecognised could lead to adverse outcomes. For this reason children with gastroenteritis who are dehydrated and clinically unwell should have a blood sugar measurement taken to exclude hypoglycaemia. Hypoglycaemia during gastroenteritis is a relatively common clinical scenario in paediatric departments in developed and less developed areas. It is difficult to estimate the true incidence from these studies because of variations in study method and definition of hypoglycaemia. The study by Hirschhorn et al 1included an assessment of blood glucose in a consecutive cohort of 73 children and found 3 (4%) children with a glucose < 2.2 mmol/L. The figure of 34% in the study by Reid et al 20035 can be ignored as it represents a convenience sample. If the definition of hypoglycaemia in the study by Reid and Losek is reduced to a level similar to the other studies (< 2.8 mmol/L) the incidence of hypoglycaemia becomes 7 of 196 (3.6%)6. In light of these results the incidence of hypoglycaemia in children with acute gastroenteritis and dehydration ranges from <1% to 8%. There is uncertainty over the aetiology of hypoglycaemia in gastroenteritis. The impact of factors such as underlying metabolic condition, malnutrition and causative organism needs further exploration. The pathogen causing gastroenteritis may not be significant as the incidence from these studies in the developing world (which controlled for malnutrition) where non-viral agents are more common is comparable to the study from the USA where a viral agent is far more likely. However both the studies in the USA did not attempt to identify aetiological agents. An episode of hypoglycaemia during an acute illness is well recognised as a presenting feature of an underlying metabolic disorder such as a fatty acid oxidation defect (e.g.MCAD). However none of the studies performed an extensive metabolic screen in all of their hypoglycaemic patients. The study by Bennish et al 4did attempt to investigate the cause of hypoglycaemia in a subgroup of 25 hypoglycaemic and matched normoglycaemic children. Similar nutritional status and pathogenic organism was observed and appropriately elevated counter-regulatory hormones (glucagon, norepinephrine and epinephrine) were found in the hypoglycaemic patients with inappropriately low gluconeogenic subtrates. They have suggested that these results represent a failure of gluconeogenesis but do not expand on the cause. Other authors blame the depletion of glycogen stores due to the inability to consume adequate substrates6. These studies suggest that a previously well child who becomes hypoglycaemic during an episode of gastroenteritis may not have an undiagnosed metabolic defect but a lack of substrate. However this would be quite an assumption to make and lack of substrate should be a diagnosis of exclusion. Therefore if hypoglycaemia is detected a thorough hypoglycaemia screen should be performed immediately along with true lab glucose. Once this screen has been performed the hypoglycaemia should be treated with specific measures.

Clinical Bottom Line

Hypoglycaemia is common in children with dehydration due to acute gastroenteritis. Children with dehydration and gastroenteritis who are clinically unwell should have a blood sugar measurement. Investigation for low blood sugar should be performed immediately to exclude an underlying metabolic condition.

References

1. Hirschhorn N, Lindenbaum J, Greenough WB, Mahmood Alam S Hypoglycaemia in children with acute diarrhoea. Lancet 1966; 2:128-132
2. Glyn-Jones R Blood sugar in infantile gastro-enteritis. SA Medical Journal 1975; 49:1474-1476
3. Majid Molla A, Hossain M, Islam R et al Hypoglycaemia: A complication of diarrhoea in childhood Indian Pediatrics 1981; 18:181-185
4. Bennish ML, Azad AK, Rahman O, Phillips RE Hypoglycemia during diarrhea in childhood NEJM 1990; 322:1357-1363
5. Reid S, McQuillan S, Losek J Hypoglycaemia complicating dehydration due to acute gastroenteritis Clinical Pediatrics 2003; 42:641-646
6. Reid S, Losek J Hypoglycaemia complicating dehydration in children with acute gastroenteritis J Emerg Medicine 2005; 2:141-145