Safe and Sufficient Glycemic Control by Using a Digital Clinical Decision Support System for Patients With Type 2 Diabetes in a Routine Setting on General Hospital Wards.

The aim was to investigate the applicability of a clinical decision support system in a real-world inpatient setting for patients with type 2 diabetes on general hospital wards.A total of 150 patients with type 2 diabetes requiring subcutaneous insulin therapy were treated with basal-bolus insulin therapy guided by a decision support system (GlucoTab) providing automated workflow tasks and suggestions for insulin dosing to health care professionals.By using the system, a mean daily blood glucose (BG) of 159 ± 32 mg/dL was achieved. 68.8% of measurements were in the target range (70 to <180 mg/dL). The percentage of BG values <40, <70, and ≥300 mg/dL was 0.02%, 2.2%, and 2.3%, respectively. Health care professionals' adherence to suggested insulin doses and workflow tasks was high (>93% and 91%, respectively).The decision support system facilitates safe and efficacious inpatient diabetes care by standardizing treatment workflow and providing decision support for basal-bolus insulin dosing.

A Mobile Computerized Decision Support System to Prevent Hypoglycemia in Hospitalized Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes management requires complex and interdisciplinary cooperation of health care professionals (HCPs). To support this complex process, IT-support is recommended by clinical guidelines. The aim of this article is to report on results from a clinical feasibility study testing the prototype of a mobile, tablet-based client-server system for computerized decision and workflow support (GlucoTab®) and to discuss its impact on hypoglycemia prevention. METHODS: The system was tested in a monocentric, open, noncontrolled intervention study in 30 patients with type 2 diabetes mellitus (T2DM). The system supports HCPs in performing a basal-bolus insulin therapy. Diabetes therapy, adverse events, software errors and user feedback were documented. Safety, efficacy and user acceptance of the system were investigated. RESULTS: Only 1.3% of blood glucose (BG) measurements were <70 mg/dl and only 2.6% were >300 mg/dl. The availability of the system (97.3%) and the rate of treatment activities documented with the system (>93.5%) were high. Only few suggestions from the system were overruled by the users (>95.7% adherence). Evaluation of the 3 anonymous questionnaires showed that confidence in the system increased over time. The majority of users believed that treatment errors could be prevented by using this system. CONCLUSIONS: Data from our feasibility study show a significant reduction of hypoglycemia by implementing a computerized system for workflow and decision support for diabetes management, compared to a paper-based process. The system was well accepted by HCPs, which is shown in the user acceptance analysis and that users adhered to the insulin dose suggestions made by the system.

Impact of errors in paper-based and computerized diabetes management with decision support for hospitalized patients with type 2 diabetes. A post-hoc analysis of a before and after study.

OBJECTIVE: Most preventable adverse drug events and medication errors occur during medication ordering. Medication order entry and clinical decision support are available on paper or as computerized systems. In this post-hoc analysis we investigated frequency and clinical impact of blood glucose (BG) documentation- and user-related calculation errors as well as workflow deviations in diabetes management. We aimed to compare a paper-based protocol to a computerized medication management system combined with clinical workflow and decision support. METHODS: Seventy-nine hospitalized patients with type 2 diabetes mellitus were treated with an algorithm driven basal-bolus insulin regimen. BG measurements, which were the basis for insulin dose calculations, were manually entered either into the paper-based workflow protocol (PaperG: 37 patients) or into GlucoTab(®)-a mobile tablet PC based system (CompG: 42 patients). We used BG values from the laboratory information system as a reference. A workflow simulator was used to determine user calculation errors as well as workflow deviations and to estimate the effect of errors on insulin doses. The clinical impact of insulin dosing errors and workflow deviations on hypo- and hyperglycemia was investigated. RESULTS: The BG documentation error rate was similar for PaperG (4.9%) and CompG group (4.0%). In PaperG group, 11.1% of manual insulin dose calculations were erroneous and the odds ratio (OR) of a hypoglycemic event following an insulin dosing error was 3.1 (95% CI: 1.4-6.8). The number of BG values influenced by insulin dosing errors was eightfold higher than in the CompG group. In the CompG group, workflow deviations occurred in 5.0% of the tasks which led to an increased likelihood of hyperglycemia, OR 2.2 (95% CI: 1.1-4.6). DISCUSSION: Manual insulin dose calculations were the major source of error and had a particularly strong influence on hypoglycemia. By using GlucoTab(®), user calculation errors were entirely excluded. The immediate availability and automated handling of BG values from medical devices directly at the point of care has a high potential to reduce errors. Computerized systems facilitate the safe use of more complex insulin dosing algorithms without compromising usability. In CompG group, missed or delayed tasks had a significant effect on hyperglycemia, while in PaperG group insufficient precision of documentation times limited analysis. The use of old BG measurements was clinically less relevant. CONCLUSION: Insulin dosing errors and workflow deviations led to measurable changes in clinical outcome. Diabetes management systems including decision support should address nurses as well as physicians in a computerized way. Our analysis shows that such systems reduce the frequency of errors and therefore decrease the probability of hypo- and hyperglycemia.

Robust PBPK/PD-Based Model Predictive Control of Blood Glucose.

GOAL: Automated glucose control (AGC) has not yet reached the point where it can be applied clinically [3]. Challenges are accuracy of subcutaneous (SC) glucose sensors, physiological lag times, and both inter- and intraindividual variability. To address above issues, we developed a novel scheme for MPC that can be applied to AGC. RESULTS: An individualizable generic whole-body physiology-based pharmacokinetic and dynamics (PBPK/PD) model of the glucose, insulin, and glucagon metabolism has been used as the predictive kernel. The high level of mechanistic detail represented by the model takes full advantage of the potential of MPC and may make long-term prediction possible as it captures at least some relevant sources of variability [4]. Robustness against uncertainties was increased by a control cascade relying on proportional-integrative derivative-based offset control. The performance of this AGC scheme was evaluated in silico and retrospectively using data from clinical trials. This analysis revealed that our approach handles sensor noise with a MARD of 10%-14%, and model uncertainties and disturbances. CONCLUSION: The results suggest that PBPK/PD models are well suited for MPC in a glucose control setting, and that their predictive power in combination with the integrated database-driven (a priori individualizable) model framework will help overcome current challenges in the development of AGC systems. SIGNIFICANCE: This study provides a new, generic, and robust mechanistic approach to AGC using a PBPK platform with extensive a priori (database) knowledge for individualization.

Standardized Glycemic Management with a Computerized Workflow and Decision Support System for Hospitalized Patients with Type 2 Diabetes on Different Wards.

BACKGROUND: This study investigated the efficacy, safety, and usability of standardized glycemic management by a computerized decision support system for non-critically ill hospitalized patients with type 2 diabetes on four different wards. MATERIALS AND METHODS: In this open, noncontrolled intervention study, glycemic management of 99 patients with type 2 diabetes (62% acute admissions; 41 females; age, 67±11 years; hemoglobin A1c, 65±21 mmol/mol; body mass index, 30.4±6.5 kg/m(2)) on clinical wards (Cardiology, Endocrinology, Nephrology, Plastic Surgery) of a tertiary-care hospital was guided by GlucoTab(®) (Joanneum Research GmbH [Graz, Austria] and Medical University of Graz [Graz, Austria]), a mobile decision support system providing automated workflow support and suggestions for insulin dosing to nurses and physicians. RESULTS: Adherence to insulin dosing suggestions was high (96.5% bolus, 96.7% basal). The primary outcome measure, percentage of blood glucose (BG) measurements in the range of 70-140 mg/dL, occurred in 50.2±22.2% of all measurements. The overall mean BG level was 154±35 mg/dL. BG measurements in the ranges of 60-70 mg/dL, 40-60 mg/dL, and <40 mg/dL occurred in 1.4%, 0.5%, and 0.0% of all measurements, respectively. A regression analysis showed that acute admission to the Cardiology Ward (+30 mg/dL) and preexisting home insulin therapy (+26 mg/dL) had the strongest impact on mean BG. Acute admission to other wards had minor effects (+4 mg/dL). Ninety-one percent of the healthcare professionals felt confident with GlucoTab, and 89% believed in its practicality and 80% in its ability to prevent medication errors. CONCLUSIONS: An efficacious, safe, and user-accepted implementation of GlucoTab was demonstrated. However, for optimized personalized patient care, further algorithm modifications are required.

Taking a Closer Look--Continuous Glucose Monitoring in Non-Critically Ill Hospitalized Patients with Type 2 Diabetes Mellitus Under Basal-Bolus Insulin Therapy.

BACKGROUND: Inpatient glucose management is based on four daily capillary blood glucose (BG) measurements. The aim was to test the capability of continuous glucose monitoring (CGM) for assessing the clinical impact and safety of basal-bolus insulin therapy in non-critically ill hospitalized patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Eighty-four patients with T2DM (age, 68±10 years; glycosylated hemoglobin, 72±28 mmol/mol; body mass index, 31±7 kg/m(2)) were treated with basal-bolus insulin. CGM was performed with the iPro(®)2 system (Medtronic MiniMed, Northridge, CA) and calibrated retrospectively. RESULTS: A remarkable consistency between CGM and BG measurements and therapy improvement was shown over the study period of 501 patient-days. The number of CGM and BG measurements (CGM/BG) in the range from 3.9-10 mmol/L increased from 67.7%/67.2% (on Day 1) to 77.5%/78.6% (on the last day) (P<0.04). The number of low glycemic episodes (3.3 to <3.9 mmol/L) during nighttime detected by CGM was 15-fold higher, and the number of episodes >13.9 mmol/L detected by CGM during night was 12.5-fold higher than the values from the BG measurements. Ninety-nine percent of data points were in the clinically accurate or acceptable Clarke Error Grid Zones A+B, and the relative numbers of correctly identified episodes of <3.9 and >13.9 mmol/L detected by CGM (sensitivity) were 47.3% and 81.5%, respectively. CONCLUSIONS: Our data exhibit a good agreement between overall CGM and BG measurements, but there were a high number of missed hypo- and hyperglycemic episodes with BG measurements, particularly during nighttime. Overall assessment of glycemic control using CGM is feasible, whereas the use of CGM for individualized therapy decisions needs further improvement.

Estimation of human leptin concentration in the subcutaneous adipose and skeletal muscle tissues.

BACKGROUND: Interstitial leptin concentrations in subcutaneous adipose and skeletal muscle tissues were determined by open-flow microperfusion. METHOD: In 12 lean male subjects (age: 25.6 ± 1.1 years), a zero flow rate experiment using different flow rates was applied. Recovery was determined by urea as an internal reference. In the no-net-flux experiments, catheters were perfused with five solutions containing different concentrations of leptin. Concentrations of interstitial leptin were calculated by applying linear regression analysis to perfusate as opposed to sampled leptin concentrations. RESULTS: The zero flow rate protocol showed significantly higher concentrations of leptin in the interstitial fluid of subcutaneous adipose compared to skeletal muscle tissue [36.8 ± 10.32 vs. 7.1 ± 2.5% of the corresponding plasma level (P = 0.018)]. The recovery of urea in the samples was comparable for all catheters [79.4 ± 6.8 vs. 83.0 ± 5.8 of the corresponding plasma level, flow rate of 0.3 µL/min; (P = ns)] and was higher when compared to leptin. In the no-net-flux protocol, the concentration of leptin in subcutaneous adipose tissue was almost identical to plasma [90. 5 ± 7.0%] and the skeletal muscle tissue concentration of leptin was 23.7 ± 2.5% of the corresponding plasma level. CONCLUSION: Open-flow microperfusion enables the estimation of leptin concentrations in subcutaneous adipose and skeletal muscle tissues in humans in vivo. This is the first documentation on the use of open-flow microperfusion to demonstrate that relevant amounts of leptin are also found in skeletal muscle tissue.

In vivo evaluation of a chip based near infrared sensor for continuous glucose monitoring.

In this paper we describe the concept and in vivo results of a minimally invasive, chip-based near infrared (NIR) sensor, combined with microdialysis, for continuous glucose monitoring. The sensor principle is based on difference absorption spectroscopy in selected wavelength bands of the near infrared spectrum (1300 nm, 1450 nm, and 1550 nm) in the 1st overtone band. In vitro measurements revealed a linear relationship between glucose concentration and the integrated difference spectroscopy signal with a coefficient of determination of 99% in the concentration range of 0-400mg/dl. The absolute error in this case is about 5mg/dl, corresponding to a relative error of about 5% for glucose concentrations larger than 50mg/dl and about 12% in the hypoglycemic range (<50mg/dl). In vivo measurements on 10 patients showed that the NIR-CGM sensor data reflects the blood reference values adequately, if a proper calibration and a signal drift correction is applied. The mean MARE (mean absolute relative error) value taken over all patient data is 13.8%. The best achieved MARE value is at 4.8%, whereas the worst lies at 25.8%, leading to a standard deviation of 5.5%.

Recirculation--a novel approach to quantify interstitial analytes in living tissue by combining a sensor with open-flow microperfusion.

We report a novel approach to quantify interstitial analytes in living tissue by combining open-flow microperfusion (OFM) with a sensor and the re-circulation method. OFM is based on the unrestricted exchange of molecules between the interstitial fluid (ISF) and a perfusion medium through macroscopic perforations that enables direct access to the ISF. By re-circulating the perfusate and monitoring the changes of the analytes' concentration with a sensor, the absolute analyte concentration in the ISF can be calculated. In order to validate the new concept, the absolute electrical conductivity of the ISF was identified in six subjects to be 1.33 ± 0.08 S/m (coefficient of variation CV = 6 %), showing the robustness of this approach. The most striking feature of this procedure is the possibility to monitor several compounds simultaneously by applying different sensors which will allow not only the determination of the concentration of a single substance in vivo but also the simultaneous dynamics of different analytes. This will open new fields in analytical chemistry, pharmacology, as well as clinical experimental research.

Automatic system testing of a decision support system for insulin dosing using Google Android.

Hyperglycaemia in hospitalized patients is a common and costly health care problem. The GlucoTab system is a mobile workflow and decision support system, aiming to facilitate efficient and safe glycemic control of non-critically ill patients. Being a medical device, the GlucoTab requires extensive and reproducible testing. A framework for high-volume, reproducible and automated system testing of the GlucoTab system was set up applying several Open Source tools for test automation and system time handling. The REACTION insulin titration protocol was investigated in a paper-based clinical trial (PBCT). In order to validate the GlucoTab system, data from this trial was used for simulation and system tests. In total, 1190 decision support action points were identified and simulated. Four data points (0.3%) resulted in a GlucoTab system error caused by a defective implementation. In 144 data points (12.1%), calculation errors of physicians and nurses in the PBCT were detected. The test framework was able to verify manual calculation of insulin doses and detect relatively many user errors and workflow anomalies in the PBCT data. This shows the high potential of the electronic decision support application to improve safety of implementation of an insulin titration protocol and workflow management system in clinical wards.

Failure to control hyperglycemia in noncritically ill diabetes patients despite standard glycemic management in a hospital setting.

BACKGROUND: Successful control of hyperglycemia has been shown to improve outcomes for diabetes patients in a clinical setting. We assessed the quality of physician-based glycemic management in two general wards, considering the most recent recommendations for glycemic control for noncritically ill patients (<140 mg/dl for premeal glucose). METHODS: Quality of glycemic management of 50 patients in two wards (endocrinology, cardiology) was assessed retrospectively by analyzing blood glucose (BG) levels, the glycemic management effort, and the online questionnaire. RESULTS: Glycemic control was clearly above the recommended target (mean BG levels: endocrinology: 175 ± 62 mg/dl; cardiology: 186 ± 68 mg/dl). When comparing the first half with the second half of the hospital stay, we found no difference in glycemic control (endocrinology: 168 ± 32 vs 164 ± 42 mg/dl, P = .67; cardiology: 174 ± 36 mg/dl vs 170 ± 42 mg/dl, P =.51) and in insulin dose (endocrinology: 15 ± 14 IU vs 15 ± 13 IU per day, P = .87; cardiology: 27 ± 17 IU vs 27 ± 18 IU per day, P = .92), despite frequent BG measurements (endocrinology: 2.7 per day; cardiology: 3.2 per day). A lack of clearly defined BG targets was indicated in the questionnaire. CONCLUSION: The recommended BG target range was not achieved in both wards. Analysis of routine glycemic management demonstrated considerable glycemic management effort, but also a lack of translation into adequate insulin therapy. Implementation of corrective measures, such as structured treatment protocols, is essential.

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.

BACKGROUND: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps. METHODS: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis. RESULTS: dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1. CONCLUSIONS: Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting.

A stepwise approach toward closed-loop blood glucose control for intensive care unit patients: results from a feasibility study in type 1 diabetic subjects using vascular microdialysis with infrared spectrometry and a model predictive control algorithm.

BACKGROUND: Glycemic control can reduce the mortality and morbidity of intensive care patients. The CLINICIP (closed-loop insulin infusion for critically ill patients) project aimed to develop a closed-loop control system for this patient group. Following a stepwise approach, we combined three independently tested subparts to form a semiautomatic closed-loop system and evaluated it with respect to safety and performance aspects by testing it in subjects with type 1 diabetes mellitus (T1DM) in a first feasibility trial. METHODS: Vascular microdialysis, a multianalyte infrared spectroscopic glucose sensor, and a standard insulin infusion pump controlled by an adaptive model predictive control (MPC) algorithm were combined to form a closed-loop device, which was evaluated in four T1DM subjects during 30-hour feasibility studies. The aim was to maintain blood glucose concentration in the target range between 80 and 110 mg/dl. RESULTS: Mean plasma glucose concentration was 110.5 ± 29.7 mg/dl. The MPC managed to establish normoglycemia within 105 ± 78 minutes after trial start and managed to maintain glucose concentration within the target range for 47% of the time. The hyperglycemic index averaged to 11.9 ± 5.3 mg/dl. CONCLUSION: Data of the feasibility trial illustrate the device being effective in controlling glycemia in T1DM subjects. However, the monitoring part of the loop must be improved with respect to accuracy and precision before testing the system in the target population.

Design of a mobile, safety-critical in-patient glucose management system.

Diabetes mellitus is one of the most widespread diseases in the world. People with diabetes usually have long stays in hospitals and need specific treatment. In order to support in-patient care, we designed a prototypical mobile in-patient glucose management system with decision support for insulin dosing. In this paper we discuss the engineering process and the lessons learned from the iterative design and development phases of the prototype. We followed a user-centered development process, including real-life usability testing from the outset. Paper mock-ups in particular proved to be very valuable in gaining insight into the workflows and processes, with the result that user interfaces could be designed exactly to the specific needs of the hospital personnel in their daily routine.

Prediction of glucose concentration in post-cardiothoracic surgery patients using continuous glucose monitoring.

OBJECTIVE: This study evaluated the predictive capability of simple linear extrapolation of continuous glucose data in postsurgical patients undergoing intensive care. METHODS: Twenty patients, both with or without an established diagnosis of diabetes mellitus, scheduled to undergo cardiothoracic surgery were included. Glucose was continuously monitored in the intensive care unit with a microdialysis-based subcutaneous glucose monitoring system. The prediction horizon (PH) with respect to a given glucose reading was calculated by extrapolating the linear trend of the glucose signal and subjected to both analytical and clinical assessment (by calculation of the average duration of consecutive positive and negative glucose signal trends, the root mean squared error [RMSE], and by insulin titration error grid [ITEG] analysis, respectively). RESULTS: In total, 609 h of continuous glucose data from 17 patients were analyzed. The average duration of consecutive positive and negative glucose signal trends was 7.97 (3.99-19.98) min (median, interquartile range). An increase in the RMSE of 0.5 mmol/L (9 mg/dL) was associated with a PH of 37 min. A strong increase in the number of data points in the unacceptable violation zone of the ITEG was associated with a PH of approximately 20 min. CONCLUSIONS: Our data provide evidence that simple linear extrapolation of glucose trend information obtained by continuous glucose monitoring can be used to predict the course of glycemia in critically ill patients for up to 20-30 min. This "glimpse into the future" can be used to proactively prevent the occurrence of adverse events.

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.

Glucose levels at the site of subcutaneous insulin administration and their relationship to plasma levels.

OBJECTIVE: To examine insulin's effect on the tissue glucose concentration at the site of subcutaneous insulin administration. RESEARCH DESIGN AND METHODS: A CMA-60 microdialysis (MD) catheter and a 24-gauge microperfusion (MP) catheter were inserted into the subcutaneous adipose tissue of fasting, healthy subjects (n = 5). Both catheters were perfused with regular human insulin (100 units/ml) over a 6-h period and used for glucose sampling and simultaneous administration of insulin at sequential rates of 0.33, 0.66, and 1.00 units/h (each rate was used for 2 h). Before and after the insulin delivery period, both catheters were perfused with an insulin-free solution (5% mannitol) for 2 h and used for glucose sampling only. Blood plasma glucose was clamped at euglycemic levels during insulin delivery. RESULTS: Start of insulin delivery with MD and MP catheters resulted in a decline of the tissue glucose concentration and the tissue-to-plasma glucose ratio (TPR) for approximately 60 min (P < 0.05). However, during the rest of the 6-h period of variable insulin delivery, tissue glucose concentration paralleled the plasma glucose concentration, and the TPR for MD and MP catheters remained unchanged at 83.2 +/- 3.1 and 77.1 +/- 4.8%, respectively. After subsequent switch to insulin-free perfusate, tissue glucose concentration and TPR increased slowly and reattained preinsulin delivery levels by the end of the experiments. CONCLUSIONS: The results show the attainment of a stable TPR value at the site of insulin administration, thus indicating that insulin delivery and glucose sensing may be performed simultaneously at the same adipose tissue site.

Use of the site of subcutaneous insulin administration for the measurement of glucose in patients with type 1 diabetes.

OBJECTIVE To simplify and improve the treatment of patients with type 1 diabetes, we ascertained whether the site of subcutaneous insulin infusion can be used for the measurement of glucose. RESEARCH DESIGN AND METHODS Three special indwelling catheters (24-gauge microperfusion [MP] catheters) were inserted into the subcutaneous adipose tissue of subjects with type 1 diabetes (n = 10; all C-peptide negative). One MP catheter was perfused with short-acting insulin (100 units/ml, Aspart) and used for insulin delivery and simultaneous glucose sampling during an overnight fast and after ingestion of a standard glucose load (75 g). As controls, the further two MP catheters were perfused with an insulin-free solution (5% mannitol) and used for glucose sampling only. Plasma glucose was measured frequently at the bedside. RESULTS Insulin delivery with the MP catheter was adequate to achieve and maintain normoglycemia during fasting and after glucose ingestion. Tissue glucose concentrations derived with the insulin-perfused catheter agreed well with plasma glucose levels. Median correlation coefficient and median absolute relative difference values were found to be 0.93 (interquartile range 0.91-0.97) and 10.9%, respectively. Error grid analysis indicated that the percentage number of tissue values falling in the clinically acceptable range is 99.6%. Comparable analysis results were obtained for the two mannitol-perfused catheters. CONCLUSIONS Our data suggest that estimation of plasma glucose concentrations from the glucose levels directly observed at the site of subcutaneous insulin infusion is feasible and its quality is comparable to that of estimating plasma glucose concentrations from glucose levels measured in insulin-unexposed subcutaneous tissue.

Clinical evaluation of subcutaneous lactate measurement in patients after major cardiac surgery.

Minimally invasive techniques to access subcutaneous adipose tissue for glucose monitoring are successfully applied in type1 diabetic and critically ill patients. During critical illness, the addition of a lactate sensor might enhance prognosis and early intervention. Our objective was to evaluate SAT as a site for lactate measurement in critically ill patients. In 40 patients after major cardiac surgery, arterial blood and SAT microdialysis samples were taken in hourly intervals. Lactate concentrations from SAT were prospectively calibrated to arterial blood. Analysis was based on comparison of absolute lactate concentrations (arterial blood vs. SAT) and on a 6-hour lactate trend analysis, to test whether changes of arterial lactate can be described by SAT lactate. Correlation between lactate readings from arterial blood vs. SAT was highly significant (r2 = 0.71, P < .001). Nevertheless, 42% of SAT lactate readings and 35% of the SAT lactate trends were not comparable to arterial blood. When a 6-hour stabilization period after catheter insertion was introduced, 5.5% of SAT readings and 41.6% of the SAT lactate trends remained incomparable to arterial blood. In conclusion, replacement of arterial blood lactate measurements by readings from SAT is associated with a substantial shortcoming in clinical predictability in patients after major cardiac surgery.

An automated discontinuous venous blood sampling system for ex vivo glucose determination in humans.

BACKGROUND: Intensive insulin therapy reduces mortality and morbidity in critically ill patients but places great demands on medical staff who must take frequent blood samples for the determination of glucose levels. A cost-effective solution to this resourcing problem could be provided by an effective and reliable automated blood sampling (ABS) system suitable for ex vivo glucose determination. METHOD: The primary study aim was to compare the performance of a prototype ABS system with a manual reference system over a 30 h sampling period under controlled conditions in humans. Two venous cannulae were inserted to connect the ABS system and the reference system. Blood samples were taken with both systems at 15, 30, and 60 min intervals and analyzed using a Beckman glucose analyzer. During the study, blood glucose levels were altered through four meal ingestions. RESULTS: The median Pearson coefficient of correlation between manually and automatically withdrawn blood samples was 0.976 (0.953-0.996). The system error was -3.327 ± 5.546% (-6.03-0.49). Through Clark error grid analysis, 420 data pairs were analyzed, showing that 98.6% of the data were in zone A and 1.4% were in zone B. Insulin titration error grid analysis revealed an acceptable treatment in 100% of cases. A 17.5-fold reduction in the occurrence of blood-withdrawal failures through occluded catheters was moreover achieved by the added implementation in the ABS system of a "keep vein open" saline infusion. CONCLUSIONS: Our study showed that the ABS system described provides a user-friendly, reliable automated means for reproducible and accurate blood sampling from a peripheral vein for blood glucose determination and thus represents a promising alternative to frequent manual blood sampling.