Efficient and safe glycaemic control with basal-bolus insulin therapy during fasting periods in hospitalized patients with type 2 diabetes using decision support technology: A post hoc analysis.

AIM: To evaluate the efficacy and safety of basal-bolus insulin therapy in managing glycaemia during fasting periods in hospitalized patients with type 2 diabetes. MATERIALS AND METHODS: We performed a post hoc analysis of two prospective, uncontrolled interventional trials that applied electronic decision support system-guided basal-bolus (meal-related and correction) insulin therapy. We searched for fasting periods (invasive or diagnostic procedures, medical condition) during inpatient stays. In a mixed model analysis, patients' glucose levels and insulin doses on days with regular food intake were compared with days with fasting periods. RESULTS: Out of 249 patients, 115 patients (33.9% female, age 68.3 ± 10.3 years, diabetes duration 15.1 ± 10.9 years, body mass index 30.1 ± 5.4 kg/m2 , HbA1c 69 ± 20 mmol/mol) had 194 days with fasting periods. Mean daily blood glucose (BG) was lower (modelled difference [ModDiff]: -0.5 ± 0.2 mmol/L, P = .006), and the proportion of glucose values within the target range (3.9-10.0 mmol/L) increased on days with fasting periods compared with days with regular food intake (ModDiff: +0.06 ± 0.02, P = .005). Glycaemic control on fasting days was driven by a reduction in daily bolus insulin doses (ModDiff: -11.0 ± 0.9 IU, P < .001), while basal insulin was similar (ModDiff: -1.1 ± 0.6 IU, P = .082) compared with non-fasting days. Regarding hypoglycaemic events (BG < 3.9 mmol/L), there was no difference between fasting and non-fasting days (χ2 0.9% vs. 1.7%, P = .174). CONCLUSIONS: When using well-titrated basal-bolus insulin therapy in hospitalized patients with type 2 diabetes, the basal insulin dose does not require adjustment during fasting periods to achieve safe glycaemic control, provided meal-related bolus insulin is omitted and correction bolus insulin is tailored to glucose levels.

Case of nasogastric tube dysfunction.

CLINICAL PRESENTATION: An elderly female patient was admitted to intensive care for prolonged vasopressor therapy and mechanical ventilation after cardiac arrest and acute percutaneous coronary intervention. Antiplatelet, thyroid hormone replacement and statin therapies were administered through a 14-French nasogastric tube (Nestlé Health Science) and enteral feeding was initiated. Correct position of the nasogastric tube was confirmed radiologically. On the seventh day in the intensive care, our patient was seen to regurgitate soft crumbs into her mouth. The blocked nasogastric tube was removed, but attempts to reinsert another tube failed.Upper GI endoscopy revealed an obstruction of the oesophagus with a milky-yellowish caseous substance 20 cm from the incisors (figure 1). The proximal part of the mass showed a central hole and ring-shaped layers resembling the cut face of a tree trunk.gutjnl;68/2/206/F1F1F1Figure 1Obstruction of the oesophagus with a milky-yellowish caseous substance. QUESTIONS: What caused the obstruction?How should we manage such a problem?

GlucoTab-guided insulin therapy using insulin glargine U300 enables glycaemic control with low risk of hypoglycaemia in hospitalized patients with type 2 diabetes.

AIMS: To investigate efficacy, safety and usability of the GlucoTab system for glycaemic management using insulin glargine U300 in non-critically ill hospitalized patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this open, non-controlled single-arm pilot study, glycaemic control at the general ward of a tertiary care hospital was guided by a mobile decision support system (GlucoTab) for basal-bolus insulin dosing using the novel basal insulin analogue insulin glargine U300 for the first time. Glycaemic control was surveilled with capillary glucose measurements and continuous glucose monitoring (CGM). The primary endpoint was efficacy of glycaemic management, defined as the percentage of blood glucose measurements within the target range of 3.9 to 7.8 mmol/L. RESULTS: A total of 30 patients with T2D (12 female; age, 67 ± 11 years; HbA1c, 70 ± 26 mmol/mol; BMI, 31.8 ± 5.6 kg/m2 ; length of study, 8.5 ± 4.5 days) were included. In total, 894 capillary glucose values and 49 846 data points of CGM were available, of which 56.1% of all measured capillary glucose values and 54.3% of CGM values were within the target area (3.9-7.8 mmol/L). Overall capillary mean glucose was 8.5 ± 1.2 and 8.4 ± 1.2 mmol/L assessed by CGM. Time within glucose target improved continuously during the course of treatment, while time within hypoglycaemia (<3.9 mmol/L) decreased substantially. The GlucoTab-suggested total daily dose was accepted by staff in 97.3% of situations. CONCLUSIONS: Treatment with GlucoTab using insulin glargine U300 in hospitalized patients with T2D is effective and safe.

Chronic gastric ulcer disease complicating selective internal radiation therapy (SIRT) in a patient with cholangiocellular carcinoma.

Selective internal radiation therapy (SIRT) is a therapeutic option for primary and metastatic liver tumors. Microspheres containing Yttrium 90, a beta-emitting radionuclide, are administered into the hepatic artery allowing selective internal radiation of a liver tumor. SIRT-related complications may appear due to migration of the radiation microspheres to organs distant from the tumor site. In order to prevent these complications, unintended non target embolization of Yttrium microspheres has to be avoided. However, data from external-beam radiation therapy (EBRT) suggests that the stomach/small bowel may actually be less radiosensitive than the liver. Gastric ulcers, a well-known SIRT-related complication, may therefore not only be caused by local radiation but also by unusual accumulation of microspheres in the submucosa and small vessel damage. We herein report a more than two- year-long persisting, highly symptomatic, non-neoplastic ulceration of the gastric antrum leading to pyloric stenosis caused by SIRT therapy with Yttrium 90 microspheres for the treatment of intrahepatic cholangiocellular carcinoma. The chronic courses of the ulcer disease together with the specific histological features highlight the pivotal role of radiation-induced small vessel damage in SIRT-induced adverse events.

Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion.

OBJECTIVE: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. PATIENTS: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. INTERVENTIONS: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. CONCLUSIONS: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition.

Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus.

BACKGROUND: Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. OBJECTIVES: To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. SEARCH METHODS: We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). SELECTION CRITERIA: We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. MAIN RESULTS: We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results.The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable.We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. AUTHORS' CONCLUSIONS: Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

Glucose control in intensive care: usability, efficacy and safety of Space GlucoseControl in two medical European intensive care units.

BACKGROUND: The Space GlucoseControl system (SGC) is a nurse-driven, computer-assisted device for glycemic control combining infusion pumps with the enhanced Model Predictive Control algorithm (B. Braun, Melsungen, Germany). We aimed to investigate the performance of the SGC in medical critically ill patients. METHODS: Two open clinical investigations in tertiary centers in Graz, Austria and Zurich, Switzerland were performed. Efficacy was assessed by percentage of time within the target range (4.4-8.3 mmol/L; primary end point), mean blood glucose, and sampling interval. Safety was assessed by the number of hypoglycemic episodes (≤2.2 mmol/L) and the percentage of time spent below this cutoff level. Usability was analyzed with a standardized questionnaire given to involved nursing staff after the trial. RESULTS: Forty medical critically ill patients (age, 62 ± 15 years; body mass index, 30.0 ± 8.9 kg/m2; APACHE II score, 24.8 ± 5.4; 27 males; 8 with diabetes) were included for a period of 6.5 ± 3.7 days (n = 20 in each center). The primary endpoint (time in target range 4.4 to 8.3 mmol/l) was reached in 88.3% ± 9.3 of the time and mean arterial blood glucose was 6.7 ± 0.4 mmol/l. The sampling interval was 2.2 ± 0.4 hours. The mean daily insulin dose was 87.2 ± 64.6 IU. The adherence to the given insulin dose advice was high (98.2%). While the percentage of time spent in a moderately hypoglycemic range (2.2 to 3.3 mmol/L) was low (0.07 ± 0.26% of the time), one severe hypoglycemic episode (<2.2 mmol/L) occurred (2.5% of patients or 0.03% of glucose readings). CONCLUSIONS: SGC is a safe and efficient method to control blood glucose in critically ill patients as assessed in two European medical intensive care units.

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.

Evaluation of an implemented new insulin chart to improve quality and safety of diabetes care in a large university hospital: a follow-up study.

OBJECTIVES: To evaluate structure, documentation, treatment quality of a new implemented standardised insulin chart in adult medical inpatient wards at a university hospital. DESIGN: A before-after study (3 to 5 months after implementation) was used to compare the quality of old versus new insulin charts. SETTING: University Hospital Graz, Austria. PARTICIPANTS: Healthcare professionals (n=237) were questioned regarding structure quality of blank insulin charts. INTERVENTIONS: A new standardised insulin chart was implemented and healthcare professionals were trained regarding features of this chart. Data from insulinised inpatients were evaluated regarding documentation and treatment quality of filled-in insulin charts (n=108 old insulin charts vs n=100 new insulin charts). MAIN OUTCOMES AND MEASURES: The primary endpoint was documentation error for insulin administration. RESULTS: Healthcare professionals reported an improved structure quality of the new insulin chart with a Likert type response scale increase in all nine items. Documentation errors for insulin administration (primary endpoint) occurred more often on old than new insulin charts (77% vs 5%, p<0.001). Documentation errors for insulin prescription were more frequent on old insulin charts (100% vs 42%) whereas documentation errors for insulin management rarely occurred in any group (10% vs 8%). Patients of both chart evaluation groups (age: 71±11 vs 71±12 years, 47% vs 42% women, 75% vs 87% type 2 diabetes for old vs new charts, respectively) had a mean of 4±2 good diabetes days. Overall, 26 vs 18 hypoglycaemic episodes (blood glucose (BG) <4.0 mmol/L (72 mg/dL), p=0.28), including 7 vs 2 severe hypoglycaemic episodes (BG <3.0 mmol/L (54 mg/dL), p=0.17) were documented on old versus new insulin charts. CONCLUSIONS: The implementation of a structured documentation form together with training measures for healthcare professionals led to less documentation errors and safe management of glycaemic control in hospitalised patients in a short time follow-up. A rollout at further medical wards is recommended, and sustainability in the long-term has to be demonstrated.

Limited Documentation and Treatment Quality of Glycemic Inpatient Care in Relation to Structural Deficits of Heterogeneous Insulin Charts at a Large University Hospital.

OBJECTIVES: Insulin charts represent a key component in the inpatient glycemic management process. The aim was to evaluate the quality of structure, documentation, and treatment of diabetic inpatient care to design a new standardized insulin chart for a large university hospital setting. METHODS: Historically grown blank insulin charts in use at 39 general wards were collected and evaluated for quality structure features. Documentation and treatment quality were evaluated in a consecutive snapshot audit of filled-in charts. The primary end point was the percentage of charts with any medication error. RESULTS: Overall, 20 different blank insulin charts with variable designs and significant structural deficits were identified. A medication error occurred in 55% of the 102 audited filled-in insulin charts, consisting of prescription and management errors in 48% and 16%, respectively. Charts of insulin-treated patients had more medication errors relative to patients treated with oral medication (P < 0.01). Chart design did support neither clinical authorization of individual insulin prescription (10%), nor insulin administration confirmed by nurses' signature (25%), nor treatment of hypoglycemia (0%), which resulted in a reduced documentation and treatment quality in clinical practice 7%, 30%, 25%, respectively. CONCLUSIONS: A multitude of charts with variable design characteristics and structural deficits were in use across the inpatient wards. More than half of the inpatients had a chart displaying a medication error. Lack of structure quality features of the charts had an impact on documentation and treatment quality. Based on identified deficits and international standards, a new insulin chart was developed to overcome these quality hurdles.

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.

Diabetes Management According to Health Status in Older Adults with Type 2 Diabetes Staying in Geriatric Care Facilities.

BACKGROUND: About 25% of adults >70 years suffer from type 2 diabetes. Due to the heterogeneity of the geriatric population, guidelines emphasize the need to individualize glycemic goals and simplify treatment strategies with the main focus of avoiding hypoglycemia. The aim of this study was to assess glycemic control in patients with type 2 diabetes in geriatric care facilities based on their individual health status. METHODS: 170 medical records of older adults with type 2 diabetes in geriatric care facilities were retrospectively assessed (64.7% female, age 80 ± 9 years; glycated hemoglobin 6.8% ± 3.6% [51 ± 16 mmol/mol]; body mass index 27.9 ± 5.8 kg/m2). Based on the individual health status, patients were allocated to three groups (healthy n = 27, complex n = 86, and poor n = 57). RESULTS: The overall blood glucose (BG) value was highest in the poor health group with 188 ± 47 mg/dL (poor) vs 167 ± 42 mg/dL (complex) vs 150 ± 34 mg/dL (healthy). BG values of 1.6% (poor) vs 2.8% (complex) vs 1.5% (healthy) of patients were below 90 mg/dL. 36.8% (poor) vs 23.4% (complex) vs 18.5% (healthy) of patients received insulin as the main diabetes therapy, but of these only 14.3% (poor) vs 20% (complex) vs 40% (healthy) were treated with basal insulin. CONCLUSIONS: Overall, BG values were higher in the poor and complex health group. There were a few low BG values in all groups. Although recommended by international guidelines, basal insulin therapy with its low complexity and low hypoglycemic risk is still underused, especially in the poor health group. Therefore, simplification of diabetes therapy should be considered further.

Interleukin-6 produced in subcutaneous adipose tissue is linked to blood pressure control in septic patients.

Cytokines are inflammatory mediators of major relevance during sepsis. Recent evidence shows that adipose tissue can produce many distinct cytokines under physiological and pathological conditions, but the role of cytokines produced in adipose tissue was not addressed in sepsis. In the present study the open-flow microperfusion (OFM) technique was used to investigate whether the cytokines produced in subcutaneous adipose tissue (SAT) of patients with severe sepsis correlate with clinical variables. Interstitial fluid effluent samples were collected using an OFM catheter inserted in the abdominal SAT of nine patients with severe sepsis. Blood samples were withdrawn concomitantly and interleukin-1beta (IL-1beta), IL-8, IL-6 and tumor necrosis factor alpha (TNF-alpha) were measured both in SAT effluent and serum samples. Different time profiles were registered for each cytokine. IL-1beta increased in a time-dependent manner, indicating a localized response against the catheter insertion. Interleukin-1beta, 6 and 8 were higher in SAT than in serum suggesting they were locally produced. Diastolic blood pressure (DBP) negatively correlated with IL-1beta, IL-6 and IL-8 in SAT indicating a possible interaction between adipose tissue inflammation and vascular tone regulation. A multiple regression analysis disclosed that mean DBP was significantly related to IL-6 concentrations in SAT (B=-43.9; R-square=0.82; P=0.002).

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.

Patients with healed diabetic foot ulcer represent a cohort at highest risk for future fatal events.

Patients with previous diabetic foot ulcer are prone to re-ulceration and (re)amputation, to various comorbidities, have significantly impaired quality of life and increased mortality. We aimed to evaluate the risk of foot related complications and mortality in a high-risk population of patients with healed diabetic foot syndrome over a decade. 91 patients with recently healed diabetic foot ulcer were invited for follow-up at 1, 6 and 11 years after inclusion. Patient characteristics at inclusion were: 40 women, 65 ± 11 years, diabetes type 1 (n = 6) or 2 (n = 85), BMI 28.5 ± 4.4 kg/m2, and HbA1c 68 ± 17 mmol/mol. Comorbidities included neuropathy (n = 91), peripheral artery disease (PAD), history of minor (n = 25) or major (n = 5, 5.5%) amputation, nephropathy (n = 40) and retinopathy (n = 53). Ulceration recurred in 71 (65%) patients, time to first recurrence was 1.8 ± 2.4 years (mean ± SD). 21 patients had to undergo (re)amputation (minor n = 19, major n = 2), time to amputation was 3.6 ± 1.9 years. Over time, 3 further major amputations were required in patients with an initial minor amputation. Thirty-three (36%) of the initially included patients completed the follow-up period of 11.0 ± 0.6 years. 58 patients (64%) died during the observational period, time to death was 5 ± 3 years in this group. We found overall high mortality of 64% throughout the follow-up period of 11 years in high-risk patients with healed diabetic foot syndrome. Presence of PAD, prior amputation and nephropathy as well as poor glycemic control were significantly predictive for death.

Tight glycaemic control by an automated algorithm with time-variant sampling in medical ICU patients.

OBJECTIVE: Tight glycaemic control (TGC) in critically ill patients improves clinical outcome, but is difficult to establish The primary objective of the present study was to compare glucose control in medical ICU patients applying a computer-based enhanced model predictive control algorithm (eMPC) extended to include time-variant sampling against an implemented glucose management protocol. DESIGN: Open randomised controlled trial. SETTING: Nine-bed medical intensive care unit (ICU) in a tertiary teaching hospital. PATIENTS AND PARTICIPANTS: Fifty mechanically ventilated medical ICU patients. INTERVENTIONS: Patients were included for a study period of up to 72 h. Patients were randomised to the control group (n = 25), treated by an implemented insulin algorithm, or to the eMPC group (n = 25), using the laptop-based algorithm. Target range for blood glucose (BG) was 4.4-6.1 mM. Efficacy was assessed by mean BG, hyperglycaemic index (HGI) and BG sampling interval. Safety was assessed by the number of hypoglycaemic-episodes < 2.2 mM. Each participating nurse filled-in a questionnaire regarding the usability of the algorithm. MEASUREMENTS AND MAIN RESULTS: BG and HGI were significantly lower in the eMPC group [BG 5.9 mM (5.5-6.3), median (IQR); HGI 0.4 mM (0.2-0.9)] than in control patients [BG 7.4 mM (6.9-8.6), p < 0.001; HGI 1.6 mM (1.1-2.4), p < 0.001]. One hypoglycaemic episode was detected in the eMPC group; no such episodes in the control group. Sampling interval was significantly shorter in the eMPC group [eMPC 117[Symbol: see text]min (+/- 34), mean (+/- SD), vs 174 min (+/- 27); p < 0.001]. Thirty-four nurses filled-in the questionnaire. Thirty answered the question of whether the algorithm could be applied in daily routine in the affirmative. CONCLUSIONS: The eMPC algorithm was effective in maintaining tight glycaemic control in severely ill medical ICU patients.

A simulation model of glucose regulation in the critically ill.

Focused research is underway to improve the delivery of tight glycaemic control at the intensive care unit. A major component is the development of safe, efficacious and effective insulin titration algorithms, which are normally evaluated in time-consuming resource-demanding clinical studies. Simulation studies with virtual critically ill patients can substantially accelerate the development process. For this purpose, we created a model of glucoregulation in the critically ill. The model includes five submodels: a submodel of endogenous insulin secretion, a submodel of insulin kinetics, a submodel of enteral glucose absorption, a submodel of insulin action and a submodel of glucose kinetics. Model parameters are estimated utilizing prior knowledge and data collected routinely at the intensive care unit to represent the high intersubject and temporal variation in insulin needs in the critically ill. Bayesian estimation combined with the regularization method is used to estimate (i) time-invariant model parameters and (ii) a time-varying parameter, the basal insulin concentration, which represents the temporal variation in insulin sensitivity. We propose a validation process to validate virtual patients developed for the purpose of testing glucose controllers. The parameter estimation and the validation are exemplified using data collected in six critically ill patients treated at a medical intensive care unit. In conclusion, a novel glucoregulatory model has been developed to create a virtual population of critically ill facilitating in silico testing of glucose controllers at the intensive care unit.

A prolonged run-in period of standard subcutaneous microdialysis ameliorates quality of interstitial glucose signal in patients after major cardiac surgery.

We evaluated a standard subcutaneous microdialysis technique for glucose monitoring in two critically ill patient populations and tested whether a prolonged run-in period improves the quality of the interstitial glucose signal. 20 surgical patients after major cardiac surgery (APACHE II score: 10.1 ± 3.2) and 10 medical patients with severe sepsis (APACHE II score: 31.1 ± 4.3) were included in this investigation. A microdialysis catheter was inserted in the subcutaneous adipose tissue of the abdominal region. Interstitial fluid and arterial blood were sampled in hourly intervals to analyse glucose concentrations. Subcutaneous adipose tissue glucose was prospectively calibrated to reference arterial blood either at hour 1 or at hour 6. Median absolute relative difference of glucose (MARD), calibrated at hour 6 (6.2 (2.6; 12.4) %) versus hour 1 (9.9 (4.2; 17.9) %) after catheter insertion indicated a significant improvement in signal quality in patients after major cardiac surgery (p < 0.001). Prolonged run-in period revealed no significant improvement in patients with severe sepsis, but the number of extreme deviations from the blood plasma values could be reduced. Improved concurrence of glucose readings via a 6-hour run-in period could only be achieved in patients after major cardiac surgery.

Clinical evaluation of alternative-site glucose measurements in patients after major cardiac surgery.

OBJECTIVE: Tight glycemic control improves outcome in critically ill patients but requires frequent glucose measurements. Subcutaneous adipose tissue (SAT) has been characterized as promising for glucose monitoring in diabetes, but it remains unknown whether it can also be used as an alternative site in critically ill patients. The present study was performed to clinically evaluate the relation of glucose in SAT compared with arterial blood in patients after major cardiac surgery. RESEARCH DESIGN AND METHODS: Forty critically ill patients were investigated at two clinical centers after major cardiac surgery. Arterial blood and SAT microdialysis samples were taken in hourly intervals for a period of up to 48 h. The glucose concentration in dialysate was calibrated using a two-step approach, first using the ionic reference technique to calculate the SAT glucose concentration (SATg) and second using a one-point calibration procedure to obtain a glucose profile comparable to SAT-derived blood glucose (BgSAT). Clinical validation of the data was performed by introducing data analysis based on an insulin titration algorithm. RESULTS: Correlation between dialysate glucose and blood glucose (median 0.80 [interquartile range 0.68-0.88]) was significantly improved using the ionic reference calibration technique (SATg vs.blood glucose 0.90 [0.83-0.94]; P < 0.001). Clinical evaluation of the data indicated that 96.1% of glucose readings from SAT would allow acceptable treatment according to a well-established insulin titration protocol. CONCLUSIONS: The results indicate good correlation between SATg and blood glucose in patients after major cardiac surgery. Clinical evaluation of the data suggests that with minor limitations, glucose from SAT can be used to establish tight glycemic control in this patient group.