Clinical Review |
Evidence Behind the WHO Guidelines: Hospital Care for Children: What is the Efficacy of Sublingual, Oral and Intravenous Glucose in the Treatment of Hypoglycaemia?
Royal Melbourne Hospital, Melbourne
Royal Children’s Hospital, Melbourne
For more information on this project to evaluate the evidence behind the WHO Hospital Care for Children, see J Trop Pediatr 2006; 52: 1–2. If you would like to suggest a topic or contribute a review, please contact Dr Julian Kelly. E-mail: <julian.kelly{at}rch.org.au>.
The World Health Organization has produced guidelines for the management of common illnesses in hospitals with limited resources. This series reviews the scientific evidence behind the WHO’s recommendations. The WHO guidelines, and more reviews are available at: http://www.ichrc.org.
This review addresses the question: What is the efficacy of sublingual, oral and intravenous glucose in the treatment of hypoglycaemia?
The WHO Pocketbook of Hospital Care for Children recommends the use of oral glucose (via Nasogastric or orally) in the form of Formula 75 or oral glucose solution (10% glucose/sucrose solution). In the event where the child presents unconscious, intravenous 10% dextrose at a rate of 5 ml kg–1 is recommended. Recent evidence has, however, suggested the possible inclusion of sublingual glucose into this management guideline.
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Introduction |
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Hypoglycaemia is an emergency condition seen commonly throughout the world. For children of developing countries, malnutrition (affecting up to 60% of all child deaths [1]), high rates of infectious diseases, poor protein intake and poor access to medical care all increase the risk and severity of hypoglycaemic presentation. A study from Bangladesh highlighted the danger of hypoglycaemia in childhood where 42.9% of children who presented to hospital with diarrhoea associated with hypoglycaemia did not survive [2].
The management of hypoglycaemia may be viewed by some as straightforward. However, for the health carer in a resource-poor setting who does not have intravenous infusion equipment or expertise, the use of intravenous dextrose may be difficult.
Sublingual glucose has the advantage of entering the systemic circulation directly through the sublingual mucosa. It therefore bypasses first-pass hepatic metabolism [3]. While the surface area of the oral mucosa is much smaller than that of the gastrointestinal tract, it is highly vascular. As a result, theoretically it is more useful than the oral route of glucose administration and has been shown to have an onset of action approaching the rate seen in intravenous administration [3]. Avoiding the intravenous pathway has many advantages including (i) not needing the expertise of setting up an intravenous infusion; (ii) not needing sterile equipment; (iii) reducing the number of painful procedures used on children; (iv) reducing the risk of transmission of blood-borne infections; (v) acting as a form of treatment not limited to the hospital setting; and (vi) reducing costs.
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Methods |
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The topic was researched using MEDLINE and the PubMed Clinical Queries framework with the following search terms: [the MeSH term hypoglycaemia OR hypoglycaemia keyword OR hypoglycaemia keyword] AND [(oral administration exploded OR sublingual administration exploded OR intravenous infusions exploded) AND (glucose exploded MeSH term)]. This resulted in 482 articles that were then limited using the ‘all child (0–18 years)’ and ‘English language’ filters resulting in 79 articles. The titles and abstracts of these articles were reviewed as well as entire articles for those that were potentially relevant to the topic of this review.
The references from relevant articles were then also reviewed for any articles that had been missed by the search. The function in Medline to search for ‘similar articles’ was employed for any key articles found.
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Results |
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Only one randomized control trial looking at all three treatment regimens was found [1]. This study looked at children aged 1–15 years from Bobo-Dioulasso (population 500 000) in Burkina Faso. It selected children who presented to a Health Centre with either (i) acute Plasmodium falciparum malaria or (ii) a moderate respiratory tract infection (a cough with no signs of pneumonia, fever <3 days duration and no change in respiratory rhythm). Those who agreed to partake in the study were treated for their acute illness, fasted overnight (after dinner) and asked to return for an assessment the following morning. Children with serum glucose of 0.5–0.8 g l–1 with no severe clinical symptoms of hypoglycaemia were enrolled in the study and were assigned to one of the following treatment groups:
- oral glucose (2.5 g of sugar);
- sublingual glucose (2.5 g of sugar via the sublingual route). This gave three subgroups according to the weight of the child (
0.1, 0.15 and 0.2 g kg–1);
- intravenous glucose (8 ml of 30% dextrose given as a bolus); and
- water.
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The sublingual route was shown to have disadvantages including (i) risk of the child swallowing too early and therefore not gaining the full benefit from the glucose. It was estimated that sugar would take
20 min to be absorbed via the sublingual route in the pilot study of this current study and so all children who swallowed in <10 min were excluded from the results. (ii) The small surface area of the sublingual route limits the dose that could be given initially and so larger children need to have repeated doses after 20 min. The intravenous route was shown to have an average of 7.3 min (–5.91–20.51) greater delay in starting treatment than the sublingual route.
Dosing
In this study, all participants received 2.5 g of glucose through various routes of administration. The optimum dose of sublingual glucose was found to be 0.15 g kg–1 (there were similar results for those receiving 0.15 and 0.2 g kg–1, but those who received 0.1 g kg–1 had a poorer kinetic profile, Table 2). The volume that can be administered via the sublingual route is limited (i.e. cannot give >0.2 g kg–1 due to the space available for this route compared with the 0.5 g kg–1 given via an intravenous route), thus repeat doses may be needed for severe hypoglycaemia. This study looked at the outcome of repeating doses to obtain the larger amount of glucose that would be needed for older children and showed that if older children (who inherently need larger amounts of glucose to obtain target concentrations) received repeated administration of sublingual glucose after 20 min, their blood glucose level was able to be maintained at >0.9 g l–1.
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Discussion |
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Study strengths
This was a randomized study with similar distribution between the four treatment groups. Outcomes had statistically significant results apart from the delay to onset of treatment.
Study weaknesses
Nutritional status or other co-morbidities of the children were not described in the study. The study was not blinded as the same physician that enrolled the patients was treating them.
This study assessed hypoglycaemia secondary to a fasting state rather than hypoglycaemia due to a severe illness, and therefore its applicability in the severely ill child is limited. While the children selected for this study had a background of either malaria or a respiratory tract infection, the study showed that having malaria did not alter the rate or extent of hypoglycaemia recovery. Adverse effects from the treatments were not assessed making it difficult to evaluate the benefits of each of the treatment regimens.
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Conclusion |
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The treatment of hypoglycaemia is traditionally limited to oral or intravenous glucose depending on the severity of the presentation. The sublingual route has been shown to be of benefit in the treatment of moderate hypoglycaemia associated with moderate respiratory tract infections or malaria. However, only one level 1b study supports this at present (Grade B evidence), and this study did not include severely ill children. The study showed that sublingual glucose causes a rapid increase in glucose concentrations with bioavailability, and a kinetic profile comparable with that of intravenous glucose in the moderately hypoglycaemic child. Further studies are needed to clarify the role for sublingual glucose in the both the community and inpatient setting.
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Notes |
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Section Editors: Trevor Duke and Julian Kelly.
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References |
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TopNotesIntroductionMethodsResultsDiscussionConclusionReferences |
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- Barennes H, Valea I, Nagot N, et al. Sublingual sugar administration as an alternative to intravenous dextrose administration to correct hypoglycemia among children in the tropics. Pediatrics (2005) 116:e648–53.
[Abstract/Free Full Text] - Bennish ML, Azad AK, Rahman O, Phillips RE, et al. Hypoglycemia during diarrhea in childhood: prevalence, pathophysiology, and outcome. N Engl J Med (1990) 322:1357–63.[Abstract]
- Hao Zhang, Jie Zhang, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet (2002) 41:661–80.[CrossRef][Web of Science][Medline]
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- What is the efficacy of sublingual glucose in children with severe illness?
- hubert Barennes, et al.
- Journal of Tropical Pediatrics, 27 Nov 2009 [Full text]
- Sublingual glucose in hypoglcaemia
- Julian Kelly
- Journal of Tropical Pediatrics, 28 Nov 2009 [Full text]
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