Blood glucose control using an artificial pancreas reduces the workload of ICU nurses

Blood glucose management is one of the important therapies in the intensive care unit (ICU). However, blood glucose management using the sliding-scale method increases the workload of ICU nurses. An artificial pancreas, STG-22, has been developed to continuously monitor blood glucose levels and to maintain them at appropriate levels. In this study, we examined the hypothesis that compared to conventional methods, blood glucose management using the STG-22 reduces the workload of ICU nurses and has a positive impact on awareness regarding the management of blood glucose. This study included 45 patients who underwent elective surgery and were treated at the ICU postoperatively. The patients were separated into the following two groups: (1) blood glucose was maintained using the STG-22 (AP group) and (2) blood glucose was maintained using the sliding-scale method (SS group). In addition, a questionnaire was developed for an awareness survey of ICU nurses (N = 20). The frequency of blood sampling and number of double checks were significantly lower in the AP group (1.3 ± 1.4 vs. 8.9 ± 8.1 times/admission, P < 0.001; 1.0 ± 1.4 vs. 9.8 ± 8.5 times/admission, P < 0.001). The time needed for glucose management per admission was significantly shorter in the AP group (9 ± 13 vs. 27 ± 24 min/admission; P = 0.003). Use of STG-22 for glucose management in the ICU increased the degree of attention given by nurses to glucose management and contributed to an improved sense of security. In conclusion, using the STG-22 in the ICU reduces the workload of ICU nurses compared to using the sliding-scale method. It also contributed to the reduction of the ICU nurses’ anxiety related to the management of blood glucose.     

Novel blood sampling method of an artificial endocrine pancreas via the cardiopulmonary bypass circuit

We tried to perform continuous blood glucose monitoring during cardiovascular surgery involving cardiopulmonary bypass using an artificial endocrine pancreas (STG-22 or -55; Nikkiso, Tokyo, Japan); however, we often encountered problems during these procedures because insufficient blood was obtained for monitoring. Thus, we started performing the blood sampling via the venous side of the cardiopulmonary bypass circuit. As a result, continuous blood glucose monitoring using an artificial endocrine pancreas was proven to be stable and reliable during cardiovascular surgery involving cardiopulmonary bypass.     

Accuracy and reliability of continuous blood glucose monitoring during pediatric cardiopulmonary bypass

Journal of Artificial Organs - The purpose of this study was to assess the accuracy and reliability of a continuous blood glucose monitoring system (artificial endocrine pancreas; STG-55, Nikkiso,...     

Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study

Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed.     

Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury

The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100–150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.     

Accuracy of roche accu-chek inform whole blood capillary, arterial, and venous glucose values in patients receiving intensive intravenous insulin therapy after cardiac surgery

Intravenous insulin protocols are increasingly common in the intensive care unit to maintain normoglycemia. Little is known about the accuracy of point-of-care glucometers for measuring glucose in this patient population or the impact of sample source (capillary, arterial, or venous whole blood) on the accuracy of glucometer results. We compared capillary, arterial, and venous whole blood glucose values with laboratory plasma glucose values in 20 patients after cardiac surgery. All 4 samples (capillary, arterial, and venous whole blood and laboratory plasma glucose) were analyzed hourly for the first 5 hours during intravenous insulin therapy in the intensive care unit. There were no significant differences between median capillary whole blood (149 mg/dL [8.3 mmol/L]) and laboratory plasma (151 mg/dL [8.4 mmol/L]) glucose levels. The median arterial (161 mg/dL [8.9 mmol/L]) and venous (162 mg/dL [9.0 mmol/L]) whole blood glucose levels were significantly higher than the median laboratory plasma glucose level. Capillary whole blood glucose levels correlate most closely with laboratory plasma glucose levels in patients receiving intensive intravenous insulin therapy after cardiac surgery.     

A case of perioperative glucose control by using an artificial pancreas in a patient with glycogen storage disease

A 57-year-old woman was diagnosed with type I glycogen storage disease in her twenties. She had undergone hepatectomy under general anesthesia with epidural anesthesia. Fifty minutes after the induction of anesthesia, a 20-gauge venous catheter was inserted in the patient’s right hand, and an artificial pancreas (STG-55, Nikkiso Co., Tokyo, Japan) was connected for continuous glucose monitoring and automatic glucose control. Insulin was infused when the blood glucose level reached 120 mg/dL or higher, and glucose was infused when the level fell to 100 mg/dL or lower. After the Pringle maneuver, the blood glucose level increased, and insulin was administered automatically via an artificial pancreas. Hypoglycemia did not occur during the operation. After total parenteral nutrition was started in the intensive care unit (ICU), the blood glucose level increased, and the artificial pancreas controlled the blood glucose level through automatic insulin administration. Thirty-four hours after admission to the ICU, the artificial pancreas was removed because the blood sampling failed. After the removal of the artificial pancreas, blood glucose level was measured every 2 h until extubation. During the ICU stay, hypoglycemia never occurred, with the average blood glucose level being 144 mg/dL. In conclusion, the use of an artificial pancreas for perioperative blood glucose management in a patient with glycogen storage disease had the beneficial effect of enabling the management of blood glucose levels without hypoglycemia.     

Two-wavelength carbon dioxide laser application for in-vitro blood glucose measurements

To develop a fast and easy clinical method for glucose measurements on whole blood samples, changes in glucose spectra are investigated varying temperature, glucose concentration, and solvent using attenuated total reflection Fourier transform infrared (ATR- FTIR) measurements. The results show a stability of the spectra at different temperatures and wavelength shifts of the absorption bands when water is replaced by blood. Because the ATR measurements are influenced by sedimentation of the red blood cells, a two-wavelength CO2 laser is used to determine the glucose concentration in whole blood samples. For this purpose, the first laser wavelength lambda(1) is tuned to the maximum of the glucose absorption band in blood at 1080 cm(-1), and the second laser wavelength lambda 2 is tuned to 950 cm(-1) for background measurements. The transmitted laser power through the optical cell containing the whole blood sample at lambda 1 and lambda 2 is used to determine the ratio. This signal correlates well with the glucose concentration in the whole blood samples. The CO2 laser measurement is too fast to be influenced by the red blood cell sedimentation, and will be a suitable method for glucose determination in whole blood.     

Microdialysis based device for continuous extravascular monitoring of blood glucose

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.     

Feasibility of precise and reliable glucose quantification in human whole blood samples by 1 tesla benchtop NMR

The standard procedure for blood glucose measurements is enzymatic testing. This method is cheap, but requires small samples of open blood with direct contact to the test medium. In principle, NMR provides non‐contact analysis of body fluids, but high‐field spectrometers are expensive and cannot be easily utilized under clinical conditions. Low‐field NMR systems with permanent magnets are becoming increasingly smaller and more affordable. The studies presented here aim at exploring the capabilities of low‐field NMR for measuring glucose concentrations in whole blood. For this purpose, a modern 1 T benchtop NMR spectrometer was used. Challenges arise from broad spectral lines, the glucose peak locations close to the water signal, low SNR and the interference with signals from other blood components. Whole blood as a sample comprises even more boundary conditions: crucial for reliable results are avoiding the separation of plasma and cells by gravitation and reliable reference values. First, the accuracy of glucose levels measured by NMR was tested using aqueous glucose solutions and commercially available bovine plasma. Then, 117 blood samples from oral glucose tolerance testing were measured with minimal preparation by simple pulse‐acquire NMR experiments. The analysis itself is the key to achieve high precision, so several approaches were investigated: peak integration, orthogonal projection to latent structure analysis and support vector machine regression. Correlations between results from the NMR spectra and the routine laboratory automated analyzer revealed an RMSE of 7.90 mg/dL for the best model. 91.5% of the model output lies within the limits of the German Medical Association guidelines, which require the glucose measurement to be within 11% of the reference method. It is concluded that spectral quantification of glucose in whole blood samples by high‐quality NMR spectrometers operating at 1 T is feasible with sufficient accuracy.     

Minimum numbers of fresh whole blood and plasma samples from patients and healthy subjects for ISI calibration of CoaguChek and RapidPointCoag monitors

The international sensitivity index (ISI) calibration of point-of-care-test (POCT) prothrombin time (PT) whole blood monitors is complex, requiring manual PT testing of 60 patients' and 20 healthy subjects' plasma samples. The possibility of reducing these numbers was studied by a Monte Carlo Bootstrap study for 2 POCT PT systems. For reduced sample numbers, this consisted of 50,000 calibrations using whole blood and plasma samples tested on the monitors with manual PT testing of plasma samples from the same blood donations. There was little effect on mean ISI by reduction of sample numbers to a total of 7, but there was progressively less certainty regarding the reliability of the calibration. Precision of the calibrations and international normalized ratio deviation were not affected markedly by reducing numbers to half As ISI calibration with the 2 POCT systems was less precise than conventional manual testing, for maximum confidence, reduction of numbers is not advised.     

Comparison of subcutaneous and intravenous continuous glucose monitoring accuracy in an operating room and an intensive care unit

Although we have used an intravenous continuous glucose monitor for blood glucose management, a previous study reported that a subcutaneous continuous glucose monitor was also reliable for use in critically ill patients. The aim of this study was to compare the subcutaneous and intravenous continuous glucose monitors. This was an observational trial (UMIN-CTR, ID:000013338). We included patients who were admitted to our intensive care units (ICU) after hepato-biliary pancreatic surgery. Continuous blood glucose measurement was performed from the beginning of the operation to ICU discharge using the intravenous continuous monitor STG-55 (Nikkiso, Tokyo, Japan) and the subcutaneous continuous monitor iPro2 (Medtronic Japan, Tokyo, Japan). The STG-55 measured the glucose level in real time, and the iPro2 measured this every 5 min. We compared glucose levels obtained using the two devices every 5 min using a Bland–Altman plot and a regression analyses. A total of 3592 comparative samples in 15 cases were analyzed. The mean glucose level measured using the STG-55 was 139 ± 21 mg/dl, and that measured using the iPro2 was 144 ± 31 mg/dl. A linear regression line had the equation of the form y = 0.225x + 106. The coefficient of determination was 0.11, and the F-test significance level was set as p < 0.01. The mean of the differences was ?5.2 mg/dl, with a 95 % agreement limit of ?67 to + 57 mg/dL. The percent error was 44 %. In conclusion, the current study suggests that subcutaneous and intravenous continuous glucose monitoring was not highly correlated during either surgery or ICU stay.     

Time and temperature effects on potassium concentration of stored whole blood from four mammalian species

The effects of time and temperature during storage of whole blood on serum and plasma potassium concentrations was examined in dogs, monkeys, rabbits and rats. The potassium concentration measurements were performed using a flame photometer. Serum and plasma potassium concentrations were affected by temperature during the storage of whole blood. In the four mammalian species tested, samples stored at 4°C indicated increasing values with the lapse of time. At 25°C, there were species differences, with blood potassium in dogs showing a high or constant value with lapse of time, whereas those of monkeys, rabbits and rats showed low or constant values. Serum potassium concentrations in the four species were higher than plasma potassium levels regardless of temperature or storage time. It was concluded that blood potassium concentration should be analysed as soon as possible after collection using a plasma sample at room temperature.     

Inertial microfluidics: Determining the effect of geometric key parameters on capture efficiency along with a feasibility evaluation for bone marrow cells sorting

Glucose measurement is one of the essential health monitoring practices for maintaining blood sugar levels. Here, we have fabricated a highly specific capacitive nano-sensor for non-enzymatic glucose detection. Capacitance measurements were carried out on polyvinyl alcohol capped copper oxide (PVA-CuO) thin films on indium tin oxide (ITO) coated glass using ARDUINO UNO. The capacitance study shows a decrease in capacitance with an increase in glucose concentrations. The applicability in real samples was performed by studying the glucose in the presence of fetal bovine serum. Most commonly found interfering agents were used for interference studies, which confirmed the capacitive nano-sensor specificity. The system was further checked for repeatability up to six readings and reproducibility up to 5 chips. The shelf-life study showed stability for four weeks of a chip. These studies indicate that this capacitance-based measurement unit can be used for reliable, rapid, and non-enzymatic detection of glucose in real sample.

     

An improved technique for the rapid continuous measurement of whole blood glucose, suitable for clinical application in an artificial endocrine pancreas.

An improved bedside technique for the continuous monitoring of glycemia is described. A linear relationship results between whole blood glucose concentration and plasma glucose levels, and allows the calibration of the system in terms of plasma glucose levels. In operation venous blood is withdrawn at a steady rate using a double-lumen catheter and directed to a continuous-flow laboratory analyzer, where glucose analysis is carried out using a modified glucose oxidase-peroxidase methodology. The improvements in this technique include: i) a reduction in the delay of the analyzer to 90 s, making it suitable for application in a system for blood glucose regulation, ii) a minimal blood requirement of 3 ml/h, permitting long-term monitoring, iii) elimination of the need for systemic anticoagulation, iv) an excellent correlation (r = 0.993) between the measured whole blood glucose and the actual plasma glucose concentration, v) an average baseline drift of +0.5 mg%/h, vi) a sensitivity loss of less than 0.1%/h, and vii) a reasonable operating cost. This technique was implemented as part of a clinical apparatus known as an artificial endocrine pancreas which has been reliably applied in clinical and animal studies.     

A new device for in vitro evaluation of thrombogenicity

A device to measure the time of coagulation of whole blood has been designed in order to facilitate testing of thrombogenicity of biomaterials. The principle of operation of the apparatus is to record the time taken for a sphere to fall through a sample of blood. The coagulation time is defined here as the time from collection of the blood sample to coagulation, coagulation having deemed to have occurred when the sphere is prevented from falling by the presence of the fibrin-cell network. The device was tested with homogeneous fluids of different viscosity, milk containing different amounts of rennin and calcium chloride and non anti-coagulated whole blood obtained from five volunteers. Repeat measurements made with each homogeneous fluid show that the variance in the transit time of the sphere is small and consistent with small dispersion. In contrast, the onset of coagulation in milk and blood samples was readily detected. The clotting of milk was highly dependant on the concentration of rennin and calcium chloride. The coagulation time of blood samples from five individuals ranged from 23 to 33 min but simultaneous measurements of samples from the same individual in two identical devices agreed to within +/-1 min in all cases. This device may be easily adapted for use in studies to determine the thromboresistance of biomaterials where the onset of coagulation of whole blood in contact with different materials may be readily compared.     

Ionized calcium: its significance and clinical usefulness

Maintenance of normal blood levels of ionized calcium (Ca2+) plays an important role in the management of the critically ill patient. Therefore, Ca2+ should be collected properly and measured reliably. The sound analytical performance of today's Ca2+ analyzers using ion-selective electrode technology have made measurements accurate and precise. The introduction of this technology allows rapid and direct analysis in whole blood or serum, resulting in an enhanced reporting time. Since the amount of heparin in the syringe was shown to lower plasma ionized calcium concentration artifactually, samples for plasma Ca2+ determination should be anticoagulated with a measured quantity of heparin. Ancillary factors in Ca2+ determination include effects of changes in sample pH, and situations where abnormal concentrations of calcium ligands are present. Many clinical situations require Ca2+ rather than total calcium measurements. Liver transplantation, citrated blood transfusions, and neonatal hypocalcemia are examples of a few such circumstances where determination of Ca2+ may be more physiologically and clinically meaningful than total calcium.     

Monitoring of Cytomegalovirus Viral Loads by Two Molecular Assays in Whole-Blood and Plasma Samples from Hematopoietic Stem Cell Transplant Recipients

Cytomegalovirus (CMV) viral loads in hematopoietic stem cell transplant (HSCT) recipients are typically monitored using quantitative molecular assays. The Roche Cobas AmpliPrep/Cobas TaqMan CMV test (Cobas CMV) has recently been cleared by the FDA for the monitoring of CMV viral loads in plasma samples from transplant patients. In this study, we compare and correlate the viral loads obtained by a laboratory-developed test (LC CMV) (using Roche analyte-specific reagents [ASR] on the LightCycler 2.0) on whole-blood specimens with those obtained on corresponding plasma and whole-blood specimens by the Cobas CMV assay. Testing was performed on 773 archived patient specimens. The strength of the agreement was good for the two assays performed on whole blood (κ = 0.6; 95% confidence interval [CI], 0.51 to 0.7) and moderate when the tests were performed on different sample types (κ = 0.54; 95% CI, 0.47 to 0.62 for the LC CMV whole blood [WB] assay versus Cobas plasma [PL], and κ = 0.57; 95% CI, 0.5 to 0.65 for the Cobas WB assay versus Cobas PL), although the difference was not statistically significant. Using a combination gold standard (i.e., a true positive was a specimen that was positive by two or more methods), the sensitivity and specificity of the assays were 78.8% and 99.3% for the LC CMV assay, 85.2% and 98.1% for the Cobas CMV WB assay, and 100% and 90.5% for Cobas CMV PL assay, respectively. A comparison of the CMV viral load trends in both plasma and whole blood from a few patients with multiple positive successive samples showed similar slopes, with differences in the slope ranging from 0.01 to 0.22. However, the absolute value for individual viral load differed markedly with whole-blood viral loads, being on average 0.5- to 1.22-log higher than those in plasma. The Cobas CMV assay provides a valid option for the monitoring of viral loads in transplant patients. Due to its increased sensitivity, the detection of CMV DNA in patients with low viral loads (i.e., those below limit of quantification [LOQ]) is increased with the Cobas CMV assay in plasma specimens. Longitudinal prospective studies will be needed to examine the clinical significance of these low-level viral loads.     

Sensitivity and Specificity of an Operon Immunochromatographic Test in Serum and Whole-Blood Samples for the Diagnosis of Trypanosoma cruzi Infection in Spain, an Area of Nonendemicity

Trypanosoma cruzi infection is an imported parasitic disease in Spain, and the majority of infected individuals are in the chronic phase of the disease. This study evaluated the sensitivity and specificity of the Operon immunochromatographic test (ICT-Operon; Simple Stick Chagas and Simple Chagas WB [whole blood]; Operon S.A., Spain) for different biological samples. Well-characterized serum samples were obtained from chagasic patients (n = 63), nonchagasic individuals (n = 95), visceral leishmaniasis patients (n = 38), and malaria patients (n = 55). Noncharacterized specimens were obtained from Latin American immigrants and individuals at risk with a clinical and/or epidemiological background: these specimens were recovered serum or plasma samples (n = 450), whole peripheral blood (n = 94), and capillary blood (n = 282). The concordance of the results by enzyme-linked immunosorbent assay and indirect immunofluorescence test was considered to be the "gold standard" for diagnosis. Serum and plasma samples were analyzed by Stick Chagas, and whole blood was analyzed by Simple Chagas WB. The sensitivity and specificity of the ICT-Operon in well-characterized samples were 100% and 97.9%, respectively. No cross-reactivity was found with samples obtained from visceral leishmaniasis patients. In contrast, a false-positive result was obtained in 27.3% of samples from malaria patients. The sensitivities of the rapid test in noncharacterized serum or plasma, peripheral blood, and capillary blood samples were 100%, 92.1%, and 86.4%, respectively, while the specificities were 91.6%, 93.6%, and 95% in each case. ICT-Operon showed variable sensitivity, depending on the kind of sample, performing better when serum or plasma samples were used. It could therefore be used for serological screening combined with any other conventional test.     

Clinical experience of an iontophoresis based glucose measuring system

Currently finger pricking is the common method of blood glucose measurement in patients with diabetes mellitus. However, diabetes patients have proven to be reluctant to check their glucose profiles regularly because of the discomfort associated with this technique. Recently, a non-invasive and continuous Reverse Iontophoresis based Glucose Monitoring Device (RIGMD) was developed in Korea. The study was conducted during the period November 2003-January 2004 on 19 in-patients. Glucose measurements were performed using RIGMD between 10 a.m. and 4 p.m. Concurrent plasma glucose levels were checked hourly and subsequently compared with RIGMD data. The mean error of RIGMD measurements was -3.45 +/- 52.99 mg/dL with a mean absolute relative error of 20+/-15.16%. Measurements obtained by RIGMD were correlated with plasma glucose levels (correlation coefficient; 0.784 (p<0.05)) and this correlation was independent of time of data collection. However, after excluding confounding variables this correlation coefficient exhibited a tendency to increase. 98.9% of the results were clinically acceptable by Clarke error grid analysis. We concluded that RIGMD does not have the reliability and accuracy required to wholly replace conventional methods. However, further technical advancements that reduce its shortcomings would make this device useful for the management of diabetes.