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

Aaron J Le Compte, Adrienne M Lynn, Jessica Lin, Christopher G Pretty, Geoffrey M Shaw, J Geoffrey Chase, Aaron J Le Compte, Adrienne M Lynn, Jessica Lin, Christopher G Pretty, Geoffrey M Shaw, J Geoffrey Chase

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.

Figures

Figure 1
Figure 1
Controller implementation overview.
Figure 2
Figure 2
BG concentration and estimated insulin sensitivity during short-term, long-term computerized insulin dosing trials and retrospective control. For the short-term trials each line in the top row of plots represents blood glucose concentration for each patient. The shaded region represents the 4–7 mmol/L target band. Each line in the bottom row of plots represents the evolution of sensitivity to exogenous insulin for each patient. For the long-term and retrospective patients summary boxplots are presented for each day of control.

References

    1. Hays SP, Smith B, Sunehag AL. Hyperglycemia Is a Risk Factor for Early Death and Morbidity in Extremely Low Birth-Weight Infants. Pediatrics. 2006;118(5):1811–1818. doi: 10.1542/peds.2006-0628.
    1. Cowett RM, Farrag HM. Selected principles of perinatal-neonatal glucose metabolism. SeminNeonatol. 2004;9(1):37–47.
    1. Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, Ong K, VanWeissenbruch M, Midgley P, Thompson M, Thio M. et al.Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study. J Pediatr. 2010;157(5):715–719. doi: 10.1016/j.jpeds.2010.04.032. e711-713.
    1. McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin. 2001;17(1):107–124. doi: 10.1016/S0749-0704(05)70154-8.
    1. Mitanchez-Mokhtari D, Lahlou N, Kieffer F, Magny J-F, Roger M, Voyer M. Both Relative Insulin Resistance and Defective Islet {beta}-Cell Processing of Proinsulin Are Responsible for Transient Hyperglycemia in Extremely Preterm Infants. Pediatrics. 2004;113(3):537–541. doi: 10.1542/peds.113.3.537.
    1. Cowett RM, Oh W, Schwartz R. Persistent glucose production during glucose infusion in the neonate. J Clin Invest. 1983;71(3):467–475. doi: 10.1172/JCI110791.
    1. Raney M, Donze A, Smith JR. Insulin infusion for the treatment of hyperglycemia in low birth weight infants: examining the evidence. Neonatal Netw. 2008;27(2):127–140. doi: 10.1891/0730-0832.27.2.127.
    1. Alsweiler JM, Kuschel CA, Bloomfield FH. Survey of the management of neonatal hyperglycaemia in Australasia. J Paediatr Child Health. 2007;43(9):632–635. doi: 10.1111/j.1440-1754.2007.01158.x.
    1. Hemachandra AH, Cowett RM. Neonatal Hyperglycemia. Pediatr Rev. 1999;20(7):16e–24e. doi: 10.1542/pir.20-7-e16.
    1. Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L. et al.Early Insulin Therapy in Very-Low-Birth-Weight Infants. N Engl J Med. 2008;359(18):1873–1884. doi: 10.1056/NEJMoa0803725.
    1. Agus MS, Javid PJ, Ryan DP, Jaksic T. Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation. J PediatrSurg. 2004;39(6):839–844.
    1. Collins JW Jr, Hoppe M, Brown K, Edidin DV, Padbury J, Ogata ES. A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance. J Pediatr. 1991;118(6):921–927. doi: 10.1016/S0022-3476(05)82212-7.
    1. Vaucher YE, Walson PD, Morrow G 3rd. Continuous insulin infusion in hyperglycemic, very low birth weight infants. J PediatrGastroenterolNutr. 1982;1(2):211–217.
    1. Binder ND, Raschko PK, Benda GI, Reynolds JW. Insulin infusion with parenteral nutrition in extremely low birth weight infants with hyperglycemia. J Pediatr. 1989;114(2):273–280. doi: 10.1016/S0022-3476(89)80797-8.
    1. Thabet F, Bourgeois J, Guy B, Putet G. Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition. ClinNutr. 2003;22(6):545–547.
    1. Ostertag S, Jovanovic L, Lewis B, Auld P. Insulin pump therapy in the very low birth weight infant. Pediatrics. 1986;78(4):625–630.
    1. Kanarek KS, Santeiro ML, Malone JI. Continuous infusion of insulin in hyperglycemic low-birth weight infants receiving parenteral nutrition with and without lipid emulsion. J Parenter Enteral Nutr. 1991;15(4):417–420. doi: 10.1177/0148607191015004417.
    1. Beardsall K, Ogilvy-Stuart AL, Frystyk J, Chen JW, Thompson M, Ahluwalia J, Ong KK, Dunger DB. Early elective insulin therapy can reduce hyperglycemia and increase insulin-like growth factor-I levels in very low birth weight infants. J Pediatr. 2007;151(6):611–617. doi: 10.1016/j.jpeds.2007.04.068.
    1. American Academy of Pediatrics Committee on Nutrition. Nutritional needs for low-birth-weight infants. Pediatrics. 1985;75:976–986.
    1. Meetze W, Bowsher R, Compton J, Moorehead H. Hyperglycemia in extremely- low-birth-weight infants. Biol Neonate. 1998;74(3):214–221. doi: 10.1159/000014027.
    1. Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Ahluwalia JS, Vanhole C, Palmer C, Midgley P, Thompson M, Cornette L, Weissenbruch M. et al.A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe) BMC Pediatr. 2007;7:29. doi: 10.1186/1471-2431-7-29.
    1. Le Compte A, Chase JG, Russell G, Lynn A, Hann C, Shaw G, Wong XW, Blakemore A, Lin J. Modeling the glucose regulatory system in extreme preterm infants. Comput Methods Programs Biomed. 2010;102(3):253–266.
    1. Chase JG, Le Compte A, Preiser JC, Shaw G, Penning S, Desaive T. Physiological modeling, tight glycemic control, and the ICU clinician: what are models and how can they affect practice? Annals of Intensive Care. 2011;1(1):11. doi: 10.1186/2110-5820-1-11.
    1. Le Compte AJ, Lee DS, Chase JG, Lin J, Lynn A, Shaw GM. Blood glucose prediction using stochastic modeling in neonatal intensive care. IEEE Trans Biomed Eng. 2010;57(3):509–518.
    1. Le Compte AJ, Chase JG, Lynn A, Hann CE, Shaw GM, Lin J. Development of blood glucose control for extremely premature infants. Comput Methods Programs Biomed. 2011;102(2):181–191. doi: 10.1016/j.cmpb.2010.03.010.
    1. Le Compte A, Chase JG, Lynn A, Hann C, Shaw G, Wong X-W, Lin J. Blood Glucose Controller for Neonatal Intensive Care: Virtual Trials Development and First Clinical Trials. J Diabetes SciTechnol. 2009;3(5):1066–1081.
    1. Chase J, Shaw GM, Wong XW, Lotz T, Lin J, Hann CE. Model-based glycaemic control in critical care - a review of the state of the possible. Biomedical Signal Processing and Control. 2006;1(1):3–21. doi: 10.1016/j.bspc.2006.03.002.
    1. Chase JG, Shaw G, Le Compte A, Lonergan T, Willacy M, Wong X-W, Lin J, Lotz T, Lee D, Hann C. Implementation and evaluation of the SPRINT protocol for tight glycaemic control in critically ill patients: a clinical practice change. Crit Care. 2008;12(2):R49. doi: 10.1186/cc6868.
    1. Lonergan T, LeCompte A, Willacy M, Chase JG, Shaw GM, Wong XW, Lotz T, Lin J, Hann CE. A simple insulin-nutrition protocol for tight glycemic control in critical illness: development and protocol comparison. Diabetes TechnolTher. 2006;8(2):191–206.
    1. Hann CE, Chase JG, Lin J, Lotz T, Doran CV, Shaw GM. Integral-based parameter identification for long-term dynamic verification of a glucose-insulin system model. Comput Methods Programs Biomed. 2005;77(3):259–270. doi: 10.1016/j.cmpb.2004.10.006.
    1. Evans A, Le Compte A, Tan CS, Ward L, Steel J, Pretty CG, Penning S, Suhaimi F, Shaw GM, Desaive T. et al.Stochastic targeted (STAR) glycemic control: design, safety, and performance. J Diabetes SciTechnol. 2012;6(1):102–115.
    1. Hewson M, Nawadra V, Oliver J, Odgers C, Plummer J, Simmer SK. Insulin infusions in the neonatal unit: Delivery variation due to adsorption.J Paed Child. Health. 2000;36(3):216–220.
    1. Garg R, Agthe AG, Donohue PK, Lehmann CU. Hyperglycemia and retinopathy of prematurity in very low birth weight infants. J Perinatol. 2003;23(3):186–194. doi: 10.1038/sj.jp.7210879.
    1. Kao LS, Morris BH, Lally KP, Stewart CD, Huseby V, Kennedy KA. Hyperglycemia and morbidity and mortality in extremely low birth weight infants. J Perinatol. 2006;26(12):730–736. doi: 10.1038/sj.jp.7211593.
    1. Alaedeen DI, Walsh MC, Chwals WJ. Total parenteral nutrition-associated hyperglycemia correlates with prolonged mechanical ventilation and hospital stay in septic infants. J PediatrSurg. 2006;41(1):239–244.
    1. Heimann K, Peschgens T, Kwiecien R, Stanzel S, Hoernchen H, Merz U. Are recurrent hyperglycemic episodes and median blood glucose level a prognostic factor for increased morbidity and mortality in premature infants </=1500 g? J Perinat Med. 2007;35(3):245–248.
    1. Chase JG, Le Compte AJ, Suhaimi F, Shaw GM, Lynn A, Lin J, Pretty CG, Razak N, Parente JD, Hann CE. et al.Tight glycemic control in critical care - The leading role of insulin sensitivity and patient variability: A review and model-based analysis. Comput Methods Programs Biomed. 2011;102(2):156–171. doi: 10.1016/j.cmpb.2010.11.006.
    1. Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics. 2000;105(5):1141–1145. doi: 10.1542/peds.105.5.1141.
    1. Ogilvy-Stuart AL, Beardsall K. Management of hyperglycaemia in the preterm infant. Arch Dis Child Fetal Neonatal Ed. 2010;95(2):F126–F131. doi: 10.1136/adc.2008.154716.
    1. Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. Br Med J. 1988;297(6659):1304–1308. doi: 10.1136/bmj.297.6659.1304.
    1. Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, Mesotten D, Casaer MP, Meyfroidt G, Ingels C. et al.Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet. 2009;373(9663):547–556. doi: 10.1016/S0140-6736(09)60044-1.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel