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Microdialysis based device for continuous extravascular monitoring of blood glucose

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Abstract

Glycemic control of intensive care patients can be beneficial for this patient group but the continuous determination of their glucose concentration is challenging. Current continuous glucose monitoring systems based on the measurement of interstitial fluid glucose concentration struggle with sensitivity losses, resulting from biofouling or inflammation reactions. Their use as decision support systems for the therapeutic treatment is moreover hampered by physiological time delays as well as gradients in glucose concentration between plasma and interstitial fluid. To overcome these drawbacks, we developed and clinically evaluated a system based on microdialysis of whole blood. Venous blood is heparinised at the tip of a double lumen catheter and pumped through a membrane based micro-fluidic device where protein-free microdialysate samples are extracted. Glucose recovery as an indicator of long term stability was studied in vitro with heparinised bovine blood and remained highly stable for 72 h. Clinical performance was tested in a clinical trial in eight healthy volunteers undergoing an oral glucose tolerance test. Glucose concentrations of the new system and the reference method correlated at a level of 0.96 and their mean relative difference was 1.9 ± 11.2%. Clinical evaluation using Clark’s Error Grid analysis revealed that the obtained glucose concentrations were accurate and clinically acceptable in 99.6% of all cases. In conclusion, results of the technical and clinical evaluation suggest that the presented device delivers microdialysate samples suitable for accurate and long term stable continuous glucose monitoring in blood.

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References

  • J.P. Bantle, W. Thomas, Glucose measurement in patients with diabetes mellitus with dermal interstitial fluid. J. Lab. Clin. Med. 130, 436–441 (1997)

    Article  Google Scholar 

  • A.M. Castejon, X. Paez, L. Hernandez, L.X. Cubeddu, Use of intravenous microdialysis to monitor changes in serotonin release and metabolism induced by cisplatin in cancer patients: comparative effects of granisetron and ondansetron. J. Pharmacol. Exp. Ther. 291, 960–966 (1999)

    Google Scholar 

  • Z. Chen, R.W. Steger, Plasma microdialysis. A technique for continuous plasma sampling in freely moving rats. J. Pharmacol. Toxicol. Methods 29, 111–118 (1993)

    Article  Google Scholar 

  • W.L. Clarke, D. Cox, L.A. Gonder-Frederick, W. Carter, S.L. Pohl, Evaluating clinical accuracy of systems for self-monitoring of blood glucose. Diabetes Care 10, 622–628 (1987)

    Article  Google Scholar 

  • F. Costa, P. Sulur, M. Angel, J. Cavalcante, V. Haile, B. Christman, I. Biaggioni, Intravascular source of adenosine during forearm ischemia in humans: implications for reactive hyperemia. Hypertension 33, 1453–1457 (1999)

    Google Scholar 

  • E.C. De Lange, A.G. De Boer, D.D. Breimer, Methodological issues in microdialysis sampling for pharmacokinetic studies. Adv Drug Deliv Rev 45, 125–148 (2000)

    Article  Google Scholar 

  • N. Dizdar, A.K. Granerus, U. Hannestad, A. Kullman, A. Ljungdahl, J.E. Olsson, B. Kagedal, L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson’s disease and a history of malignant melanoma. Acta Neurol. Scand. 100, 231–237 (1999a)

    Article  Google Scholar 

  • N. Dizdar, A. Kullman, B. Norlander, J.E. Olsson, B. Kagedal, Human pharmacokinetics of L-3, 4-dihydroxyphenylalanine studied with microdialysis. Clin. Chem. 45, 1813–1820 (1999b)

    Google Scholar 

  • N.R. Ekberg, N. Wisniewski, K. Brismar, U. Ungerstedt, Measurement of glucose and metabolites in subcutaneous adipose tissue during hyperglycemia with microdialysis at various perfusion flow rates. Clin. Chim. Acta 359, 53–64 (2005)

    Article  Google Scholar 

  • M. Ellmerer, M. Haluzik, J. Blaha, J. Kremen, S. Svacina, W. Toller, J. Mader, L. Schaupp, J. Plank, T.R. Pieber, Clinical evaluation of alternative site glucose measurement in patients after major cardiac surgery. Diabetes Care 29, 1275–1281 (2006)

    Article  Google Scholar 

  • J.P. Elshoff, S. Laer, Development of an intravenous microdialysis method for pharmacokinetic investigations in humans. J. Pharmacol. Toxicol. Methods 52, 251–259 (2005)

    Article  Google Scholar 

  • V.R. Kondepati, H.M. Heise, Recent progress in analytical instrumentation for glycaemic control in diabetic and critically ill patients. Anal. Bioanal. Chem. 388, 545–563 (2007)

    Article  Google Scholar 

  • E. Kulcu, J.A. Tamada, G. Reach, R.O. Potts, M.J. Lesho, Physiological differences between interstitial glucose and blood glucose measured in human subjects. Diabetes Care 26, 2405–2409 (2003)

    Article  Google Scholar 

  • V. Lodwig, L. Heinemann, Glucose Monitoring Study Group. Continuous glucose monitoring with glucose sensors: calibration and assessment criteria. Diabetes Technol. Ther. 5, 573–587 (2003)

    Article  Google Scholar 

  • J. Lourido, P. Ederoth, N. Sundvall, U. Ungerstedt, C.H. Nordstrom, Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care. Scand. J. Clin. Lab. Invest. 62, 285–292 (2002)

    Article  Google Scholar 

  • M.T. O’Connell, F. Tison, N.P. Quinn, P.N. Patsalos, Clinical drug monitoring by microdialysis: application to levodopa therapy in Parkinson’s disease. Br. J. Clin. Pharmacol. 42, 765–769 (1996)

    Article  Google Scholar 

  • X. Paez, L. Hernandez, Blood microdialysis in humans: a new method for monitoring plasma compounds. Life Sci. 61, 847–856 (1997)

    Article  Google Scholar 

  • P.N. Patsalos, M.T. O’Connell, H.C. Doheny, J.W. Sander, S.D. Shorvon, Antiepileptic drug pharmacokinetics in patients with epilepsy using a new microdialysis probe: preliminary observations. Acta Neurochir. Suppl. 67, 59–62 (1996)

    Google Scholar 

  • W. Regittnig, M. Ellmerer, G. Fauler, G. Sendlhofer, Z. Trajanoski, H.J. Leis, L. Schaupp, P. Wach, T.R. Pieber, Assessment of transcapillary glucose exchange in human skeletal muscle and adipose tissue. Am. J. Physiol. Endocrinol. Metab. 285, E241–E251 (2003)

    Google Scholar 

  • J.N. Roe, B.R. Smoller, Bloodless glucose measurements. Crit. Rev. Ther. Drug Carrier Syst. 15, 199–241 (1998)

    Google Scholar 

  • H. Rosdahl, K. Hamrin, U. Ungerstedt, J. Henriksson, Metabolite levels in human skeletal muscle and adipose tissue studied with microdialysis at low perfusion flow. Am. J. Physiol. 274, E936–E945 (1998)

    Google Scholar 

  • C. Sauernheimer, K.M. Williams, K. Brune, G. Geisslinger, Application of microdialysis to the pharmacokinetics of analgesics: problems with reduction of dialysis efficiency in vivo. J. Pharmacol. Toxicol. Methods 32, 149–154 (1994)

    Article  Google Scholar 

  • R. Schaller, F. Feichtner, H. Köhler, M. Bodenlenz, J. Plank, A. Wutte, J.K. Mader, M. Ellmerer, R. Hellmich, H. Wedig, R. Hainisch, T.R. Pieber, L. Schaupp, A novel automated discontinuous venous blood monitoring system for ex vivo glucose determination in humans. Biosens. Bioelectron. 24, 2239–2245 (2009)

    Article  Google Scholar 

  • L. Schaupp, M. Ellmerer, G.A. Brunner, A. Wutte, G. Sendlhofer, Z. Trajanoski, F. Skrabal, T.R. Pieber, P. Wach, Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion. Am. J. Physiol. Endocrinol. Metab. 276, E401–E408 (1999)

    Google Scholar 

  • S. Skyler, Continuous glucose monitoring: an overview of its development diabetes. Technol. Ther. 11(Suppl 1), S5–S10 (2009)

    Google Scholar 

  • F. Sternberg, C. Meyerhoff, F.J. Mennel, H. Mayer, F. Bischof, E.F. Pfeiffer, Does fall in tissue glucose precede fall in blood glucose? Diabetologia 39, 609–612 (1996)

    Article  Google Scholar 

  • H. Stjernstrom, T. Karlsson, U. Ungerstedt, L. Hillered, Chemical monitoring of intensive care patients using intravenous microdialysis. Intensive Care Med. 19, 423–428 (1993)

    Article  Google Scholar 

  • U. Ungerstedt, Microdialysis—principles and applications for studies in animals and humans. J. Intern. Med. 230, 365–373 (1991)

    Article  Google Scholar 

  • G. van den Berghe, P. Wouters, F. Weekers, C. Verwaest, F. Bruyninckx, M. Schetz, D. Vlasselaers, P. Ferdinande, P. Lauwers, R. Bouillon, Intensive insulin therapy in the critically ill patients. N. Engl. J. Med. 345, 1359–1367 (2001)

    Article  Google Scholar 

  • G. van den Berghe, P.J. Wouters, K. Kesteloot, D.E. Hilleman, Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients. Crit. Care Med. 34, 612–616 (2006)

    Google Scholar 

  • R.K. Verbeeck, Blood microdialysis in pharmacokinetic and drug metabolism studies. Adv. Drug Deliv. Rev. 45, 217–228 (2000)

    Article  Google Scholar 

  • D. Vlasselaers, L. Schaupp, I. van den Heuvel, J. Mader, M. Bodenlenz, M. Suppan, P. Wouters, M. Ellmerer, G. van den Berghe, Monitoring blood glucose with microdialysis of interstitial fluid in critically ill children. Clin. Chem. 53, 536–537 (2007)

    Article  Google Scholar 

  • C. Weller, M. Linder, A. Macaulay, A. Ferrari, G. Kessler, Continuous in vivo determination of blood glucose in human subjects. Ann. N. Y. Acad. Sci. 87, 658–668 (1960)

    Article  Google Scholar 

  • I.M.E. Wentholt, A.A.M. Hart, J.B.L. Hoekstra, J.H. Devries, How to assess and compare the accuracy of continuous glucose monitors? Diabetes Technol. Ther. 10, 57–68 (2008)

    Article  Google Scholar 

  • H. Yang, Q. Wang, W.F. Elmquist, The design and validation of a novel intravenous microdialysis probe: application to fluconazole pharmacokinetics in the freely-moving rat model. Pharm. Res. 14, 1455–1460 (1997)

    Article  Google Scholar 

  • R.A. Yokel, D.D. Allen, D.E. Burgio, P.J. McNamara, Antipyrine as a dialyzable reference to correct differences in efficiency among and within sampling devices during in vivo microdialysis. J. Pharmacol. Toxicol. Methods 27, 135–142 (1992)

    Article  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge financial support from the European Commission under the CLINICIP project (contract no. 506965 within the 6th Framework program). Thanks to my love Iris Yukon.

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The authors declare to have no competing interests.

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Correspondence to Franz Feichtner.

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Feichtner, F., Schaller, R., Fercher, A. et al. Microdialysis based device for continuous extravascular monitoring of blood glucose. Biomed Microdevices 12, 399–407 (2010). https://doi.org/10.1007/s10544-010-9396-3

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