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      Pilot study of a model-based approach to blood glucose control in very-low-birthweight neonates

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          Abstract

          Background

          Hyperglycemia often occurs in premature, very low birthweight infants (VLBW) due to immaturity of endogenous regulatory systems and the stress of their condition. Hyperglycemia in neonates has been linked to increased morbidities and mortality and occurs at increasing rates with decreasing birthweight. In this cohort, the emerging use of insulin to manage hyperglycemia has carried a significant risk of hypoglycemia. The efficacy of blood glucose control using a computer metabolic system model to determine insulin infusion rates was assessed in very-low-birth-weight infants.

          Methods

          Initial short-term 24-hour trials were performed on 8 VLBW infants with hyperglycemia followed by long-term trials of several days performed on 22 infants. Median birthweight was 745 g and 760 g for short-term and long-term trial infants, and median gestational age at birth was 25.6 and 25.4 weeks respectively. Blood glucose control is compared to 21 retrospective patients from the same unit who received insulin infusions determined by sliding scales and clinician intuition. This study was approved by the Upper South A Regional Ethics Committee, New Zealand (ClinicalTrials.gov registration NCT01419873).

          Results

          Reduction in hyperglycemia towards the target glucose band was achieved safely in all cases during the short-term trials with no hypoglycemic episodes. Lower median blood glucose concentration was achieved during clinical implementation at 6.6 mmol/L (IQR: 5.5 – 8.2 mmol/L, 1,003 measurements), compared to 8.0 mmol/L achieved in similar infants previously (p < 0.01). No significant difference in incidence of hypoglycemia during long-term trials was observed (0.25% vs 0.25%, p = 0.51). Percentage of blood glucose within the 4.0 – 8.0 mmol/L range was increased by 41% compared to the retrospective cohort (68.4% vs 48.4%, p < 0.01).

          Conclusions

          A computer model that accurately captures the dynamics of neonatal metabolism can provide safe and effective blood glucose control without increasing hypoglycemia.

          Trial Registration

          ClinicalTrials.gov registration NCT01419873

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          Most cited references31

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          Stress-induced hyperglycemia.

          Stress hyperglycemia is common and likely to be associated with at least some of the same complications as hyperglycemia in true diabetes mellitus, such as poor wound healing and a higher infection rate. The predominant cause is the intense counterregulatory hormone and cytokine responses of critical illness, often compounded by excessive dextrose administration, usually as TPN. Although randomized data suggesting benefit of controlling hyperglycemia in hospitalized patients are paltry, prospective controlled trials are feasible and should be initiated. In the interim, the practice at the authors' institution is to use insulin to lower plasma glucose concentrations to a safe range of 150 mg/dL to 200 mg/dL in all patients.
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            Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia.

            There has been considerable debate over whether asymptomatic neonatal hypoglycaemia results in neurological damage. In a detailed multicentre study of 661 preterm infants hypoglycaemia was found to be common. Moderate hypoglycaemia (plasma glucose concentration less than 2.6 mmol/l) occurred in 433 of the infants and in 104 was found on three to 30 separate days. There was considerable variation among the centres, implying differences in decisions to intervene. The number of days on which moderate hypoglycaemia occurred was strongly related to reduced mental and motor development scores at 18 months (corrected age), even after adjustment for a wide range of factors known to influence development. When hypoglycaemia was recorded on five or more separate days adjusted mental and motor developmental scores at 18 months (corrected age) were significantly reduced by 14 and 13 points respectively, and the incidence of neurodevelopmental impairment (cerebral palsy or developmental delay) was increased by a factor of 3.5 (95% confidence interval 1.3 to 9.4). These data suggest that, contrary to general belief, moderate hypoglycaemia may have serious neurodevelopmental consequences, and reappraisal of current management is urgently required.
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              Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds.

              The definition of clinically significant hypoglycemia remains one of the most confused and contentious issues in contemporary neonatology. In this article, some of the reasons for these contentions are discussed. Pragmatic recommendations for operational thresholds, ie, blood glucose levels at which clinical interventions should be considered, are offered in light of current knowledge to aid health care providers in neonatal medicine. Future areas of research to resolve some of these issues are also presented.
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                Author and article information

                Journal
                BMC Pediatr
                BMC Pediatr
                BMC Pediatrics
                BioMed Central
                1471-2431
                2012
                7 August 2012
                : 12
                : 117
                Affiliations
                [1 ]Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand
                [2 ]MBChB, FRACP, Neonatal Department, Christchurch Women’s Hospital, Christchurch, New Zealand
                [3 ]Department of Medicine, University of Otago, Otago, New Zealand
                [4 ]MbChB, FJFICM, Department of Intensive Care, Christchurch Hospital, Christchurch School of Medicine and Health Science, University of Otago, Otago, New Zealand
                Article
                1471-2431-12-117
                10.1186/1471-2431-12-117
                3465220
                22871230
                16578f86-3663-4518-9a82-c09ec023592f
                Copyright ©2012 Le Compte et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 February 2012
                : 26 July 2012
                Categories
                Research Article

                Pediatrics
                premature birth,insulin,control,hyperglycemia,insulin sensitivity
                Pediatrics
                premature birth, insulin, control, hyperglycemia, insulin sensitivity

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