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TECHNOLOGY, COMPUTING, AND SIMULATION

The Accuracy of a Continuous Blood Glucose Monitor During Surgery

Koichi Yamashita, MD, PhD^*, Takehiro Okabayashi, MD, PhD, Takeshi Yokoyama, DDS, PhD^*, Tomoaki Yatabe, MD^*, Hiromichi Maeda, MD, Masanobu Manabe, MD, PhD^*, and Kazuhiro Hanazaki, MD, PhD

From the *Department of Anesthesiology and Critical Care Medicine; and First Department of Surgery, Kochi Medical School, Kochi, Japan.

Address correspondence and reprint requests to Kochi Yamashita, MD, PhD, Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi 783-8505, Japan. Address e-mail to koichiya{at}kochi-u.ac.jp.

	Abstract

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BACKGROUND: Protocols for tight control of blood glucose can be difficult to achieve in the surgical setting, especially when relying upon intermittent blood glucose testing. A continuous blood glucose monitoring system can facilitate blood glucose management. In the present study, we compared blood glucose measured continuously (STG-22^TM, Nikkiso, Tokyo, Japan), during surgery with coincident measurements obtained intermittently using a conventional laboratory glucometer (ABL^TM 800FLEX (Radiometer Medical Aps, Brnshj, Denmark). The goal of the study was to determine the reliability and accuracy of the continuous method during surgery.

MATERIAL AND METHODS: Twenty-nine patients scheduled for routine surgery with general anesthesia were enrolled in this study. After anesthetic induction, a 20G IV catheter was inserted in a peripheral forearm vein and connected to the continuous blood glucose monitor. A radial arterial catheter was also inserted from which samples for blood glucose estimation were obtained by an anesthesiologist, following an established protocol of discarding 3 mL of blood before the actual blood sampling. Blood glucose was measured by ABL^TM 800FLEX immediately after sampling. One hundred points of paired blood glucose values were obtained, which were compared using Bland and Altman analysis.

RESULTS: Bias and upper and lower limits of agreement were –2.6, 23, and –28, respectively. The percentage error of the lower/upper limits of agreement was 21% and 18%, respectively.

DISCUSSION AND CONCLUSIONS: The blood glucose measurements obtained continuously agreed with the coincident intermittent measurements within 21%. The STG-22^TM may still be useful for following changes continuously and reducing the frequency of intermittent measurement, but the need for testing samples with a reliable device is not eliminated.

	Introduction

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Tight control of glucose has been reported to reduce mortality in critically ill patients.1–4 However, despite frequent blood glucose testing, it has been shown that blood glucose may exceeded 180 mg/dL in about 45% of intensive care unit patients.5 The insulin infusion protocol itself is usually complex, requiring education and continuing staff monitoring for correct adherence. A previous report showed that the percentage of patients with severe hypoglycemia, defined as glucose values under 59 mg/dL was about 1% and that hypoglycemic events could not be avoided during intensive insulin therapy with intermittent blood glucose sampling.6 Therefore, a continuous blood glucose monitor would be beneficial to maintain target blood glucose levels.

Two types of continuous glucose monitoring systems are currently in use: a continuous subcutaneous glucose monitor and a continuous blood glucose monitor. The continuous subcutaneous glucose monitoring system might be less invasive than a continuous IV blood monitoring system in terms of bleeding, infection, thrombus, nerve damage, etc. However, the precision of both these types of continuous glucose monitors is controversial, especially in critically ill patients.7,8 Chase et al.9 reported that a continuous subcutaneous glucose monitor had a larger error than blood glucose measured by pinprick methods and could not be used in the clinical setting without computational model parameter fitting and semi-closed, or automated, feedback control systems. STG-22^TM (Nikkiso, Tokyo, Japan) has been used as an artificial pancreas and was designed to measure blood glucose continuously. Therefore, STG-22^TM might be a useful option for intensive insulin therapy.

In the present study, we compared blood glucose levels measured by STG-22^TM, a continuous blood glucose monitor, with coincident measurements using the ABL^TM 800FLEX (Radiometer Medical Aps, Brnshj, Denmark), a conventional blood glucose assessment system. The goal of the study was to determine the reliability and accuracy of the continuous method during surgery.

	METHODS

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Twenty-nine patients undergoing scheduled surgeries (hepatectomy, pancreaticoduodenectomy, vascular surgery, off-pump coronary artery bypass grafting, and others) were enrolled in this study after obtaining approval from the hospital ethics committee and patients’ written informed consent. After anesthetic induction, a 20G IV catheter (Insyte^TM, 20GA 1.16IN, Becton Dickinson Infusion Therapy System, Sandy, UT) was inserted into a peripheral forearm vein and connected to the STG-22^TM for continuous blood glucose monitoring. A radial arterial catheter was inserted for intermittent blood glucose sampling. Samples were obtained every 2 h during surgery after an established protocol of discarding 3 mL of blood before withdrawing the actual blood sample by a single senior anesthesiologist. Blood glucose was immediately measured in these radial artery samples by ABL^TM 800FLEX. One hundred points of paired blood glucose values were obtained.

Equipment
The STG-22^TM provides continuous blood glucose monitoring through a dual lumen catheter blood sampling technique (Fig. 1), high-quality roller pump (multichannel pump) and a glucose sensor electrode with glucose oxidase membrane (Yellow Springs, Dayton, OH) (Fig. 2). Before starting blood glucose monitoring, a two-point calibration was done using the standard solution for internal calibration (glucose concentration: 0 mg/dL) and standard glucose solution (200 mg/dL). During blood glucose monitoring, internal calibration using the standard solution for internal calibration was automatically done every 4 h. After calibration of the equipment, blood was sampled continuously from the peripheral vein at a rate of 2 mL/h and continuously diluted with a heparinized isotonic solution. The diluted blood was further diluted with an isotonic buffer solution of phosphoric acid, pH 7.4, after which the glucose sensor electrode was exposed to the sampled blood. The multichannel pump and the glucose sensor electrode both had an accuracy of ±5%.

View larger version (9K): [in this window] [in a new window]   Figure 1. Dual lumen catheter blood sampling technique. A dual lumen catheter was inserted into a 20G IV catheter. Heparinized isotonic solution 8 mL/h was infused through a short catheter and then 10 mL/h of sample blood was drawn from a long catheter simultaneously. As a result, 2 mL/h of sample blood was drawn for blood glucose monitoring and the blood was diluted by heparinized isotonic solution.

View larger version (21K): [in this window] [in a new window]   Figure 2. The whole circuit of the STG-22TM. Blood was drawn into the device through a 20G IV catheter. The blood was diluted by heparinized isotonic solution and buffer solution. The sample blood then reached the glucose sensor electrode.

ABL^TM 800FLEX (Conventional Intermittent Glucose Monitor)
The ABL^TM 800FLEX can measure pH and blood gases in combination with oximetry, electrolytes, and metabolite variables. Glucose concentration is measured by the glucose-oxidase methods from 95 µl of whole blood, providing results within 2 min. These measurements are recommended by the National Committee for Clinical Laboratory Standards.10 The primary working standards are prepared from Standard Reference Material produced by the National Institute of Standards and Technology 917a (D-glucose); these primary standards being used to determine the glucose concentration of secondary standards. The accuracy of the glucose electrode is within 5%.

Statistical Analysis
Data are presented as mean ± sd. Bland and Altman analysis11,12 was used to compare the bias (the mean of the differences) and limits of agreement (bias ± 2 sd of bias) between blood glucose measured by STG-22^TM and ABL^TM 800FLEX (STG-22^TM–ABL^TM 800FLEX). The percentage errors of the lower and upper limits of agreement were also calculated.

	RESULTS

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The 29 patients undergoing scheduled surgery (15 hepatectomy, 6 pancreaticoduodenectomy, 4 vascular surgery, 1 off-pump coronary artery bypass grafting, and others) included 22 men and 7 women, 71 ± 11 yr of age, 157 ± 8 cm in height, and 55 ± 11 kg in weight. Bias and upper and lower limits of agreement were –2.6, 23, and –28 mg/dL, respectively. The percentage errors of the lower and upper limits of agreement were 21% and 18%, respectively (Table 1, Fig. 3). Blood coagulation in the device was not observed during the study.

View larger version (24K): [in this window] [in a new window]   Figure 3. Bland–Altman plot of blood glucose measurements from STG-22TM and ABL-800TM.

	DISCUSSION

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This study shows that STG-22^TM may be useful for tight glucose control in surgical patients because of its continuity; however, the need for testing samples with another reliable device is not eliminated due to the percentage error of the continuous method, which was found to be 21%.

In the present study, we evaluated blood glucose measured by STG-22^TM in comparison with that measured by ABL^TM 800FLEX. We did so without a preliminary validation study, because ABL^TM 800FLEX is used worldwide and its accuracy in comparison with conventional laboratory glucose assessments has been established under the quality control of the National Committee for Clinical Laboratory Standards.

STG-22^TM (Nikkiso, Tokyo, Japan) is the original artificial endocrine pancreas with a closed-loop glycemic control system that provides continuous IV blood glucose monitoring through a glucose sensor electrode and subsequent automatic insulin and glucose infusions, to maintain appropriate blood glucose levels.13 Although STG-22^TM has been used as a laboratory machine to evaluate insulin resistance in patients with insulinomas,14 no studies have been conducted evaluating blood glucose control using the STG-22^TM in critically ill patients.

Blood glucose measured by STG-22^TM was influenced by two factors. Because a diluted blood sample has to be measured in this device, maintaining a constant flow rate by multichannel pump in blood sampling and heparinized isotonic solution infusion was important; second is the accuracy of the blood glucose electrode. The accuracy of blood pump and the blood glucose electrode were both within 5%. Therefore, the main challenge to measuring blood glucose continuously is correctly sampling blood from the peripheral forearm vein.

Dual lumen catheter blood sampling is a novel technique for avoiding blood coagulation while providing easy blood sampling from a peripheral forearm vein without a tourniquet. However, this technique has not been fully investigated in clinical settings, especially in critically ill patients. In critically ill and surgical patients, peripheral circulatory insufficiency due to hypovolemia often occurs. In the present study, however, blood coagulation in the device was not observed in the continuous blood sampling procedure. We think that this novel technique enables anesthesiologists to measure blood glucose continuously during surgery.

Eight points of blood glucose measured by STG-22^TM exceeded the upper or lower limits of agreement (±2 sd) especially with values over 200 mg/dL of blood glucose. The reason why STG-22^TM over- or underestimated blood glucose at these points might have been due to a time lag in measuring blood glucose. It took about 4 min for the sampling blood from the tip of the IV catheter to reach the glucose sensor electrode. Blood glucose levels of more than 200 mg/dL might indicate that the patients were suffering from insulin resistance, induced by various surgical stimulations. In such situations, blood glucose fluctuates easily with the surgical procedure so the discrepancies observed may not be exclusively due to a limitation of the sensor.

The Bland–Altman analysis (Fig. 3) indicates that the limits of agreement were greater as blood glucose measurements exceeded 200. Even in the range between 80 and 200, the limits of agreement approached 20%, which may not be sufficiently accurate to guide insulin therapy. Furthermore, since no data were obtained from patients who were hypoglycemic it was not possible to evaluate the value of the continuous sensor for detecting hypoglycemia during intensive insulin therapy. Continuous measurements were possible using the STG-22^TM sensor. It may not be useful as a trend monitor, but confirmation of measurements by a more reliable device are likely needed to guide therapeutic decisions.

Another limitation of the device is the need for continuous blood sampling. Although only 2 mL/h of blood are required to measure blood glucose continuously, this may be a significant volume, especially for certain critically ill patients, patients with anemia and/or a child. Technical advances are needed to permit accurate measurements of blood glucose using smaller blood samples.

	CONCLUSIONS

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The blood glucose measurements obtained continuously agreed with the coincident intermittent measurements within 21%. The STG-22^TM may be useful for following changes continuously in surgical patients and reducing the frequency of intermittent measurement, but the need for testing samples with a reliable device is not eliminated.

	Footnotes

 
Accepted for publication September 11, 2007.

	REFERENCES

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1. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Feedinande P, Lauwers P, Bouilon R. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345:1359–67[Abstract/Free Full Text]
2. Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality in critically ill patients. JAMA 2003;290:2041–7[Abstract/Free Full Text]
3. Toft P, Jorgensen HS, Toennesen E, Christiansen C. Intensive insulin therapy to non-cardiac ICU patients: a prospective study. Eur J Anaesthesiol 2006;23:705–9[Web of Science][Medline]
4. Ingles C, Debaveye Y, Milants L, Buelens E, Peeraer A, Devriendt Y, Vanhoutte T, Damme AV, Schetz M, Wouters PJ, Van den Berghe G. Strict blood glucose control with insulin during intensive care after cardiac surgery: impact on 4-years survival, dependency on medical acre, and quality-of-life. Eur Heart J 2006;10:1093–102
5. Kee CA, Tomalty JA, Cline J, Novick RJ, Stitt L. Change in practice patterns in the management of diabetic cardiac surgery patients. Can J Cardiovascular Nursing 2006;16:20–7
6. Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 2004;79:992–1000[Abstract/Free Full Text]
7. Hovorka R. Continuous glucose monitoring and closed-loop systems. Diabet Met 2006;23:1–12
8. Corstjens AM, Ligtenberg JJM, Van der Horst ICC, Spanjersberg R, Lind JSW, Tulleken JE, Meertens JHJM, Zijilstra JG. Accuracy and feasibility of point-of-care and continuous blood glucose analysis in critically ill ICU patients. Critical Care 2006;10:R135[Medline]
9. Chase JG, Hann CE, Jackson M, Lin J, Lotz T, Wong XW, Shaw GM. Integral-based filtering of continuous glucose sensor measurements for glycaemic control in critical care. Comput Methods Programs Biomed 82;2006:238–47[Web of Science][Medline]
10. NCCLS Publication RS1-A, Villenova, Pa.: NCCLS
11. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;8476:307–10
12. Bland JM, Altman DG. Statistics notes: calculation correlation coefficients with repeated observations: Part 2—correlation between subjects. BMJ 1995;310:633[Free Full Text]
13. Kono T, Hanazaki K, Yazawa K, Ashizawa S, Fisher WE, Wang X-P, Nose Y, Brunicaidi FC. Pancreatic polypeptide administration reduces insulin requirements of artificial pancreas in pancreatectomized dogs. Artif Organs 2005;29:83–9[Web of Science][Medline]
14. Hiramatsu S, Sako Y, Mimura K, Iwashige K, Taniuchi S, Umeda F, Nawata H. Impared feedback inhibition of insulin secretion by hyperinsulinemia in patients with insulinoma. Endocr J 1995;42:39–42[Web of Science][Medline]

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