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Background: Severe perioperative hyperglycemia (SH) is a proven risk factor for postoperative complications after craniotomy. To reduce this risk, it has been proposed to implement the standardized clinical protocol for scheduled perioperative blood glucose concentration (BGC) monitoring. This would be followed by intravenous (IV) insulin infusion to keep BGC below 180 mg/dl in the perioperative period. The aim of this prospective observational study was to assess the impact of this type of protocol on the postoperative infection rate in patients undergoing elective craniotomy., Methods: A total of 42 patients were prospectively enrolled in the study. Protocol included scheduled BGC monitoring in the perioperative period and rapid-acting insulin IV infusion when intraoperative SH was detected. The diagnosis of infection (wound, pulmonary, blood stream, urinary tract infection or central nervous system infection) was established according to CDC criteria within the first postoperative week. A previously enrolled group of patients with sporadic BGC monitoring and subcutaneous insulin injections for SH management was used as a control group., Results: An infectious complication (i.e., pneumonia) was diagnosed only in one patient (2 %) in the prospective group. In comparison with the control group, a decrease in the risk of postoperative infection was statistically significant with OR = 0.08 [0.009 - 0.72] (p = 0.02). Implementation of the perioperative BGC monitoring and the correction protocol prevented both severe hyperglycemia and hypoglycemia with BGC < 70 mg/dl., Conclusion: Scheduled BGC monitoring and the use of low-dose insulin infusion protocol can decrease the postoperative infection rate in patients undergoing elective craniotomy. Future studies are needed to prove the causality of the implementation of such a protocol with an improved outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We evaluated the feasibility of real-time continuous glucose monitoring (CGM) for titrating continuous intravenous insulin infusion (CII) to manage hyperglycemia in postoperative individuals in the cardiovascular intensive care unit and assessed their accuracy, nursing acceptance, and postoperative individual satisfaction., Methods: Dexcom G6 CGM devices were applied to 59 postsurgical patients with hyperglycemia receiving CII. A hybrid approach combining CGM with periodic point-of-care blood glucose (POC-BG) tests with two phases (initial-ongoing) of validation was used to determine CGM accuracy. Mean and median absolute relative differences and Clarke Error Grid were plotted to evaluate the CGM accuracy. Surveys of nurses and patients on the use of CGMs experience were conducted and results were analyzed., Results: In this cohort (mean age 64, 32% female, 32% with diabetes) with 864 paired POC-BG and CGM values analyzed, mean and median absolute relative difference between POC-BG and CGM values were 13.2% and 9.8%, respectively. 99.7% of paired CGM and POC-BG were in Zones A and B of the Clarke Error Grid. Responses from nurses reported CGMs being very or quite convenient (n = 28; 93%) and it was favored over POC-BG testing (n = 28; 93%). Majority of patients (n = 42; 93%) reported their care process using CGM as being good or very good., Conclusion: This pilot study demonstrates the feasibility, accuracy, and nursing convenience of adopting CGM via a hybrid approach for insulin titration in postoperative settings. These findings provide robust rationale for larger confirmatory studies to evaluate the benefit of CGM in postoperative care to improve workflow, enhance health outcomes, and cost-effectiveness., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LA, YKL, LFS, YH, CAD, PA, FA, SK, ED, ND, YQ, RF, NHE, and RG have no conflicting interest to disclose. RPB received grant support to University of Michigan from Dexcom.

Background: We aim to provide a practical guidance on the use of intravenous insulin infusion for managing inpatient hyperglycemia., Methods and Results: This document was formulated based on the review of available literature and personal experience of authors. We have used various case scenarios to illustrate variables which should be taken into account when deciding adjustments in infusion rate, including but not restricted to ambient blood glucose level and magnitude of blood glucose change in the previous hour., Conclusion: The guidance can be generalized to any situation where dedicated protocols are lacking, trained manpower is not available and resource constraints are present., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest associated with this manuscript., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study aims to evaluate the impact of Microburst Insulin Infusion (MII) treatment on Type 1 and 2 diabetic patients' HbA1c, lipids, peripheral neuropathy, and patient-reported health status. Methods: We reviewed clinical charts, including lab results, for more than 80 diabetic and pre-diabetic patients treated at one U.S. outpatient clinic in St. Louis, Missouri between February 2017 and December 2019. Data included patient demographics, treatment data, lab and neuropathy tests, and self-reported patient health status questions. The explanatory variable was number of months of MII treatment. Treatments are 3-4 h in length, with two intensive infusions the first week and one treatment each week thereafter, usually for 12 weeks total. Lab tests were at 12-week intervals. Generalized linear modeling and t-tests assessed the significance of differences between patients' baseline lab values, neuropathy measures, and health status before treatment vs. after final treatment. Results: Number of MII treatments per patient ranged from 1 to 262, over 1-24 months. Time in MII treatment was significantly associated with reductions in HbA1c by nearly 0.04 points per month, and triglycerides declined 3 points per month. Neuropathy measures of large toe vibratory sensation (clanging tuning fork) improved significantly, as did patient-reported health and feelings of improvement since beginning treatment. Discussion: The MII therapy appears to be efficacious in treating diabetic patients, particularly those with complications like neuropathy. Our findings affirmed several other studies. We uniquely incorporated patient health questionnaires, and empirically studied MII treatment efficacy for diabetes in a population large enough to permit statistically valid inferences. With multiple waves of data for over 80 patients, this is one of the most extensive quantitative studies of microburst insulin infusion therapy conducted to date, with protocols more uniformly implemented and survey instruments more consistently administered by the same clinical team. Given the advances in insulin infusion therapy brought by MII, and early indications of its efficacy, the time is right for more in-depth studies of the outcomes patients can achieve, the physiological mechanisms by which they occur, MII's comparative effectiveness vis-à-vis traditional treatments, and cost-effectiveness., Competing Interests: SH previously consulted on a clinical improvement and strategic planning project with Mitokon Health Center, the St. Louis clinic from which the de-identified data were obtained. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Howard, Zhang, Linomaz, Lam, Qian, Thurman and BeLue.)

Background: Hyperglycemia in acute coronary syndrome (ACS) is linked to raised morbidity and mortality. Insulin administration using insulin infusion protocols (IIP) is the preferred strategy to control hyperglycemia in critically ill patients. To date, no specific IIP has been identified as the most efficient for achieving glycemic control., Aim: to compare glycemic achievements (safety) (primary objective), and coronary and other clinical outcomes (efficacy) (secondary objective) by hyperglycemia management in Cardiac Care Unit (CCU) using computerized Atlanta Protocol (Group (I)) versus paper-based Joint British Diabetes Societies (JBDS) For Inpatient Care Protocol (Group (II))., Patients and Methods: The study was done on 100 ACS patients admitted to Alexandria Main University hospital CCU with RBG >180 mg/dL. They were randomized into the 2 groups in a 1:1 ratio. CBG was measured hourly for 72 hours and was managed by IV insulin infusion., Results: Group (I) showed statistically significant less mean time for target BG achievement (3.52 ± 1.53hours), lower incidence of Level 1 hypoglycemia (2%) than Group (II) (4.76 ± 2.33 hours, 22%, p = 0.013, 0.002 respectively) and statistically significant less mean number of episodes above the glycemic target after its achievement than Group (II) (p < 0.001). Regarding Level 2 hypoglycemia the difference was not significant statistically., Conclusion: Both protocols successfully maintained target BG level with low incidence of clinically significant hypoglycemia, however, the computerized Atlanta protocol achieved better glycemic outcomes. We recommend the use of the computerized Atlanta protocol in CCU rather than JBDS for Inpatient Care Protocol whenever this is feasible., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Insulin adsorption to clinical materials has been well observed, but not well quantified. Insulin adsorption reduces expected and actual insulin delivery and is unaccounted for in insulin therapy or glycemic control. It may thus contribute to poor control and high glycemic variability. This research quantifies the problem in the context of clinical use., Method: Experimental insulin adsorption data from literature is used to calculate insulin delivery and total insulin adsorption capacities for polyethylene (PE) and polyvinal chloride (PVC) lines at clinically relevant flow rates and concentrations., Results: Insulin adsorption capacity decreased hyperbolically with flow rate for both PE and PVC, where low flow scenarios result in greater insulin adherence to infusion lines. When the infusion flow rate was halved from 1 to 0.5 mL/h, twice as much insulin adsorbed to the line. Insulin loss to adsorption resulted in up to ~50% of intended insulin not delivered over 24 hours in a low flow and low concentration context., Conclusion: Material capacity for insulin adsorption is not constant, but increases with decreasing flow. Different materials have different adsorption capacities. In low flow and low concentration contexts, such as in neonatal or pediatric intensive care, insulin loss to adsorption represents a significant proportion of daily insulin delivery, which needs to be accounted for.

Background: The use of an intravenous insulin infusion protocol (IIP) is recommended for management of hyperglycemia in the intensive care unit (ICU); however, limited evidence of comparison has been made with subcutaneous (SC) insulin regimens. Objective: This study aims to evaluate the safety and effectiveness of an IIP compared with SC insulin regimens in an ICU patient sample since the implementation of an IIP using a computerized clinical-decision support tool. Methods: This investigation was a retrospective cohort study of patients who were treated for hyperglycemia while admitted to any of the ICUs at a Veterans Affairs Medical Center. Patients who were treated with either an IIP or a scheduled SC insulin regimen between May 1, 2015, and May 25, 2016, were included for evaluation. Results: Blood glucose (BG) was within the normoglycemia range (70-180 mg/dL) for 63.0% of the measurements in patients treated with an IIP (n = 171) compared with 45.7% in those treated with SC insulin regimens (n = 121; P < 0.01). Overall, patients managed with an IIP had a lower proportion of hypoglycemic BG measurements (1.2% vs 2.1%, P < 0.01), a lower proportion of hyperglycemic BG measurements (35.8% vs 52.2%, P < 0.01), and a lower mean BG (172.4 vs 194.3 mg/dL, P < 0.01). Conclusion and Relevance: The results of this study suggest that an IIP in a sample of adult ICU patients was associated with better BG control and lower occurrence of hypoglycemia compared with SC insulin regimens.

Purpose: This study examined the effect of permissive underfeeding compared to target feeding and intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT) on the inflammatory mediators monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), and tissue factor (TF) in critically ill patients., Methodology: This was a substudy of a 2 × 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients were randomized into permissive underfeeding compared to target feeding groups and into IIT compared to CIT groups (ISRCTN96294863). In this substudy, we included 91 patients with almost equal numbers across randomization groups. Blood samples were collected at baseline and at days 3, 5, and 7 of an ICU stay. Linear mixed models were used to assess the differences in MCP-1, sICAM-1, and TF across randomization groups over time., Results: Baseline characteristics were balanced across randomization groups. Daily caloric intake was significantly higher in the target feeding than in the permissive underfeeding groups ( P -value < 0.01), and the daily insulin dose was significantly higher in the IIT than in the CIT groups ( P -value < 0.01). MCP-1, sICAM-1, and TF did not show any significant difference between the randomization groups, while there was a time effect for MCP-1. Baseline sequential organ failure assessment (SOFA) score and platelets had a significant effect on sICAM-1 ( P -value < 0.01). For TF, there was a significant association with age ( P -value < 0.01)., Conclusions: Although it has been previously demonstrated that insulin inhibits MCP-1, sICAM-1 in critically ill patients, and TF in non-critically ill patients, our study demonstrated that IIT in critically ill patients did not affect these inflammatory mediators. Similarly, caloric intake had a negligible effect on the inflammatory mediators studied.

Background Standard therapy of diabetic ketoacidosis (DKA) in pediatrics involves intravenous (IV) infusion of regular insulin until correction of acidosis, followed by transition to subcutaneous (SC) insulin. It is unclear what laboratory marker best indicates correction of acidosis. We hypothesized that an institutional protocol change to determine correction of acidosis based on serum bicarbonate level instead of venous pH would shorten the duration of insulin infusion and decrease the number of pediatric intensive care unit (PICU) therapies without an increase in adverse events. Methods We conducted a retrospective (pre/post) analysis of records for patients admitted with DKA to the PICU of a large tertiary care children's hospital before and after a transition-criteria protocol change. Outcomes were compared between patients in the pH transition group (transition when venous pH≥7.3) and the bicarbonate transition group (transition when serum bicarbonate ≥15 mmol/L). Results We evaluated 274 patient records (n=142 pH transition group, n=132 bicarbonate transition group). Duration of insulin infusion was shorter in the bicarbonate transition group (18.5 vs. 15.4 h, p=0.008). PICU length of stay was 3.2 h shorter in the bicarbonate transition group (26.0 vs. 22.8 h, p=0.04). There was no difference in the number of adverse events between the groups. Conclusions Transitioning patients from IV to SC insulin based on serum bicarbonate instead of venous pH led to a shorter duration of insulin infusion with a reduction in the number of PICU therapies without an increase in the number of adverse events.

Aims: Although diabetic ketoacidosis (DKA) commonly presents as a pure diabetic ketoacidosis (PDKA), up to 30% of cases may be associated with a mixed hypochloremic metabolic alkalosis (HMA). It is unknown whether there is a difference in treatment outcomes between these two entities. We evaluated an insulin infusion protocol (IIP), previously validated for hyperglycemia management in ICU's, for the management of PDKA and HMA., Materials and Methods: A retrospective case series/cohort study of 41 DKA admissions was further characterized as having PDKA or HMA. HMA was defined in those having an elevated delta-delta gradient (ΔAG-ΔHCO3) ≥ 5 mmol/L and base excess chloride (BE Cl ) > 2.7 mmol/L. The main outcome measures were times to recovery of glucose levels to ≤250 mg/dL and of anion gap to ≤12 mmol/L., Results: The initial serum glucose was 553 ± 265 mg/dL, serum bicarbonate of 8.8 ± 5.1 mmol/L, and venous pH 7.13 ± 0.2). Recovery of glucose occurred in 5 h: 25 min (±3 h:39min), and for anion gap in 11 h:25 min (±6 h:56min). HMA compared with PDKA had a delayed recovery of serum glucose (7 h: 23min ± 3 h: 35min vs. 4 h: 31min ± 3:h:21min, p = 0.017), which was due to the higher initial level of glucose (p = 0.02) rather than level of BE Cl (p = 0.17). There was no difference in time to anion gap closure between the PDKA and HMA., Conclusions: Correction of hyperglycemia and acidosis in PDKA as well as in HMA was managed through the IIP. The simultaneous fluid and electrolyte management corrected the hypochloremic alkalosis., (Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: This review examines algorithm design features that may reduce risk for hypoglycemia while preserving glycemic control during intravenous insulin infusion. We focus principally upon algorithms in which the assignment of the insulin infusion rate (IR) depends upon maintenance rate of insulin infusion (MR) or a multiplier., Recent Findings: Design features that may mitigate risk for hypoglycemia include use of a mid-protocol bolus feature and establishment of a low BG threshold for temporary interruption of infusion. Computer-guided dosing may improve target attainment without exacerbating risk for hypoglycemia. Column assignment (MR) within a tabular user-interpreted algorithm or multiplier may be specified initially according to patient characteristics and medical condition with revision during treatment based on patient response. We hypothesize that a strictly increasing sigmoidal relationship between MR-dependent IR and BG may reduce risk for hypoglycemia, in comparison to a linear relationship between multiplier-dependent IR and BG. Guidelines are needed that curb excessive up-titration of MR and recommend periodic pre-emptive trials of MR reduction. Future research should foster development of recommendations for "protocol maxima" of IR appropriate to patient condition.

Background: To assess the efficacy of a unified hyperglycemia and diabetic ketoacidosis (DKA) insulin infusion protocol (IIP), based on an Excel algorithm and implemented as an electronic order set, in achieving glycemic targets and minimizing hypoglycemia., Methods: An IIP was instituted in medical and surgical intensive care units for post-cardiac surgery (PCS) and other stress hyperglycemia (SH), diabetes hyperglycemia (DH), and DKA. The IIP initiated therapeutic insulin rates at elevated blood glucose (BG), and decreased insulin when target range was achieved. A convenience sample (n=62) was studied; 20 PCS, 15 with DH, 9 with SH, 8 with diabetes on vasopressors, 7 with diabetes on glucocorticoids and 3 with DKA were assessed., Results: The protocol maintained BG at 144±24.7mg/dL for PCS and 167±36mg/dL for patients with diabetes mellitus. It maintained acceptable target range (ATR) (100mg/dL-180mg/dL) 89% of the time for PCS and 67% of the time for patients with diabetes mellitus. There were no measurements of BG<70mg/dL. The protocol lowered the BG at a similar rate and time period in those with diabetes, DKA and those with or without vasopressors or glucocorticoids. To determine long-term efficacy, a retrospective review of Point of Care (POC) RALS (Remote Automated Data System) BG data 2 years post implementation demonstrated fewer episodes of hypoglycemia<70mg/dL and hyperglycemia>240mg/dL and more BG values within ATR., Conclusions: This IIP maintained ATR without hypoglycemia for patients in the ICU setting without requiring complex nursing calculations., (Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

The link between energy availability, turnover of energy substrates and the onset of inflammation in dairy cows is complex and poorly investigated. To clarify this, plasma inflammatory variables were measured in mid-lactating dairy cows allocated to three groups: hyperinsulinemic hypoglycaemic clamp, induced by insulin infusion (HypoG, n = 5); hyperinsulinemic euglycaemic clamp, induced by insulin and glucose infusion (EuG; n = 6); control, receiving a saline solution infusion (NaCl; n = 6). At 48 h after the start of i.v. infusions, two udder quarters per cow were challenged with 200 μg of E. coli lipopolysaccharide (LPS). Individual blood samples were taken before clamps, before LPS challenge (i.e. 48 h after clamps) and 6.5 h after. At 48 h, positive acute phase proteins (posAPP) did not differ among groups, whereas albumin and cholesterol (index of lipoproteins), negative APP (negAPP), were lower (p < 0.05) in EuG compared to NaCl and HypoG. The concentration of IL-6 was greater in EuG (p < 0.05) but only vs. HypoG. At 6.5 h following LPS challenge, IL-6 increased in the NaCl and EuG clamps (p < 0.05), while TNF-α increased (p < 0.05) in the EuG only. Among the posAPP, haptoglobin markedly increased in EuG (p < 0.05), but not in NaCl (p = 0.76) and in HypoG; ceruloplasmin tended to decline during LPS challenge, the reduction was significant when all animals were considered (p < 0.05). Conversely, all the negAPP showed a marked reduction 6.5 h after LPS challenge in the three groups. In conclusion, EuG caused an inflammatory status after 48-h infusion (i.e. decrease of negAPP) and induced a quicker acute phase response (e.g. marked rise of TNF-α, IL-6) after the intramammary LPS challenge. These data suggest that the simultaneous high availability of glucose and insulin at the tissue-level makes dairy cows more susceptible to inflammatory events. In contrast, HypoG seems to attenuate the inflammatory response., (Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.)

Objectives: To investigate the effectiveness of computerised insulin dosing calculators for the management of continuous insulin infusions in adult patients who underwent cardiac surgery., Method: A systematic review was conducted. The CINAHL, MEDLINE and Cochrane databases were searched for primary studies that compared a computerised insulin dosing calculator to a paper protocol. The main outcome measures were mean Blood Glucose Level (BGL), time to achieve BGL target range, time spent within BGL target range, the incidence of hyperglycaemia and the incidence of hypoglycaemia., Results: Five studies were included in the final review. Pooled data demonstrated significant improvements in mean BGL (MD -14.24, 95% CI -26.93 to -1.55), p=0.03 and significantly lower rates of hypoglycaemia (OR 0.038, 95% CI: 0.16-0.90), p=0.03 amongst the computer calculator groups in comparison to the paper protocol groups. No significant difference in the incidence of severe hypoglycaemia was demonstrated (OR 0.21, 95% CI 0.02-1.79), p=0.15. No difference was found in time (hours) to reach target blood glucose range (MD -1.47, 95% CI -3.75 to 0.81), p=0.21., Conclusion: There is some evidence to support the use of computerised insulin dosing calculators for insulin infusion management within critical care environments., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Although insulin resistance (IR) is a key factor in the pathogenesis of type 2 diabetes (T2D), the precise role of insulin in the development of IR remains unclear. Therefore, we investigated whether chronic basal insulin infusion is causative in the development of glucose intolerance., Methods: Normoglycemic lean rats surgically instrumented with i.v. catheters were infused with insulin (3mU/kg/min) or physiological saline for 6weeks. At infusion-end, plasma insulin levels along with glucose tolerance were assessed., Results: Six weeks of insulin infusion induced glucose intolerance and impaired insulin response in healthy rats. Interestingly, the effects of chronic insulin infusion were completely normalized following 24h withdrawal of exogenous insulin and plasma insulin response to glucose challenge was enhanced, suggesting improved insulin secretory capacity. As a result of this finding, we assessed whether the effects of insulin therapy followed by a washout could ameliorate established glucose intolerance in obese rats. Obese rats were similarly instrumented and infused with insulin or physiological saline for 7days followed by 24h washout. Seven day-insulin therapy in obese rats significantly improved glucose tolerance, which was attributed to improved insulin secretory capacity and improved insulin signaling in liver and skeletal muscle., Conclusion: Moderate infusion of insulin alone is sufficient to cause glucose intolerance and impair endogenous insulin secretory capacity, whereas short-term, intensive insulin therapy followed by insulin removal effectively improves glucose tolerance, insulin response and peripheral insulin sensitivity in obese rats., General Significance: New insight into the link between insulin and glucose intolerance may optimize T2D management., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to assess the effect of intravenous (IV) insulin administration in children with severe acute asthma (SAA) and hyperglycemia on IV salbutamol consumption and length of stay (LOS) in a pediatric intensive care unit (PICU)., Methods: Retrospective, descriptive study of the clinical course before and after implementation of an insulin protocol for the treatment of hyperglycemia (i.e. blood glucose >8 mmol/L or 144 mg/dL, respectively) in the PICU of a tertiary care university hospital. Admissions between 1994 and 2010 were reviewed. The insulin protocol was introduced in 2006., Results: A total of 131 pediatric patients with SAA complicated by hyperglycemia requiring IV salbutamol were included. Severity of illness before and after implementation of the insulin protocol did not significantly differ. The insulin-treated patient group had significantly higher maximum blood glucose levels and higher cumulative IV salbutamol dose than the non-treated group. There were no differences between these groups in the duration of IV salbutamol administration and LOS., Conclusions: In view of the lack of difference in outcomes and considering that the insulin protocol is labor-intensive, the question is whether this protocol is efficacious for the treatment of pediatric SAA associated with hyperglycemia.

Background: In acute coronary syndrome, the use of intravenous insulin infusions (IVII) to control hyperglycaemia is based on limited evidence of survival benefit., Aims: To compare 7 day survival for patients receiving IVII compared with those receiving routine care to control admission hyperglycaemia (>=11 mmol/l) in acute coronary syndrome., Methods and Results: We used matched propensity analysis to examine observational data from the MINAP database between 2008 and 2012. We matched 5974 pairs of patients. We separately examined outcomes for ST elevation (STEMI) and non ST segment elevation (NSTEMI) infarctions, and those without known diabetes and those with type 2 diabetes. Survival benefit from the use of IVII was seen only in patients with STEMI not known to have diabetes at admission (adjusted hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.64-0.92), p=0.005). Those with STEMI and existing type 2 diabetes who received IVII showed similar outcomes to routine care (HR 0.99 (95% CI 0.80-1.23), p=0.931). In patients with NSTEMI IVII was associated with significantly worse adjusted 7 day survival outcome than routine care, regardless of diabetes status; for those without known diabetes, HR 1.50 (95% CI 1.04-2.16), p=0.029, and for those with type 2 diabetes, HR 1.35 (95% CI 1.08-1.70), p=0.010., Conclusion: As used in current clinical practice to treat hyperglycaemia in acute coronary syndromes, IVII appears to be of benefit only for patients with STEMI who are not known to have diabetes. IVII is associated with adverse early outcomes in patients with NSTEMI., (© The European Society of Cardiology 2014.)

Background: A number of insulin infusion algorithms, with varying methods and effects, have been developed to guide the management of postoperative hyperglycemia in critically ill patients., Objectives: The objective of this study was to investigate the effect of insulin therapy algorithms on blood glucose levels in patients in critical care environments following cardiac surgery., Inclusion Criteria: Types of participants: Adult patients aged 18 or older who were admitted to a critical care environment after cardiac surgery and who received insulin therapy for glycemic control during the acute postoperative phase of their admission. Types of intervention: The intervention of interest was continuous intravenous insulin therapy. Types of studies: Experimental study designs including randomized controlled trials, non-randomized controlled trials and controlled before and after studies published in the English language were included in this review. Types of outcomes: Primary outcomes of interest included objective measures of glycemic control and secondary outcomes of interest included the incidence of adverse events., Search Strategy: The search aimed to find both published and unpublished studies through electronic databases, reference lists, key reports and the World Wide Web. An extensive search was undertaken for the following databases: Medline, CINAHL, PubMed, Embase, Scopus, the Cochrane Library, Dare, Social Science Index, ProQuest, and MedNar. Databases were searched up to March 2014., Methodological Quality: All studies selected were assessed by two reviewers independently for methodological quality prior to inclusion in the review using the standardized Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument critical appraisal tool. Any disagreements that arose between the reviewers were resolved through discussion., Data Collection: Quantitative data was extracted from papers included in the review using the standardized data extraction tool from Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. All results were subject to double data entry., Data Synthesis: Statistical pooling of the data in meta-analysis was carried out using Review Manager meta-analysis software where possible. Odds Ratios, Relative Risks, Weighted Means Differences and their 95% Confidence Interval were calculated where appropriate. Where statistical pooling was not possible due to the heterogeneity of the studies the findings are presented in narrative form including tables and figures., Results: Thirteen studies were included in the final review. Pooled data demonstrated significantly improved mean blood glucose levels (Weighted Means Differences -27.24, 95% Confidence Interval: -27.77 - -26.72), p < 0.00001 and achievement of target blood glucose levels range (Relative Risks 1.43, 95% Confidence Interval: 1.18 - 1.72), p = 0.0002, among participants who received the paper nomogram continuous intravenous insulin method of glucose control compared to the bolus regime group. Studies that investigated paper nomogram directed continuous intravenous insulin compared to computer calculator directed continuous intravenous insulin demonstrated a statistically significant improved mean blood glucose levels (Weighted Means Differences -23.74, 95% Confidence Interval: -24.45 - -23.02), p <0.00001 and higher percentage of time in which glucose levels were within the target range in the computer calculator group. A significantly lower incidence (p < 0.05) of hyperglycemia was observed in the computerized calculator directed CII group (1.3 ± 1.2%) compared to the paper nomogram CII (6.5 ± 2%)., Conclusions: There is evidence of a benefit of continuous insulin infusions for patients following cardiac surgery with the computer calculator CII method achieving optimal glycemic control., Implications for Practice: The implementation of a computer calculator CII algorithm allows for individualized patient treatment. However, given the limited availability of the computer based algorithm, the implementation of a paper based algorithm would be justified., Implications for Research: Future studies to compare the methods of computer calculator directed CII to paper nomogram directed CII should be undertaken using more rigorous research designs such as randomized controlled trials with sufficiently powered sample sizes. Definitions for both hypoglycemia and hyperglycemia should be standardized., (The Joanna Briggs Institute.)

A new measurement system enables combination of continuous glucose monitoring (CGM) and insulin infusion. A sensor system comprising an optical glucose biosensor and an optical oxygen sensor is integrated into the insulin infusion catheter of an insulin pump. Both sensors rely on near infrared (NIR) phosphorescent porphyrin dyes, wherefore the signals can be read out transcutaneous and non-invasively with a custom-built phase fluorometer measurement module. The spectral properties of the indicator dyes and the optical setup of the measurement module were optimized to enable independent read-out in two channels. Dynamic ranges from 0 mmHg to 160 mmHg oxygen and 0mg/dL to 360 mg/dL glucose (LOD 2mg/dL) are covered by the oxygen and the glucose sensor, respectively. In-vivo measurements in pigs demonstrate good correlation of reference blood glucose levels and glucose values obtained with the presented sensor system. The evaluation of the clinical accuracy of the system with Clarke Error Grid Analysis showed similar results to CGM-devices currently on the market., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.

One major obstacle that limits the lifespan of insulin infusion pumps is surmounting the tissue site reaction at the device implantation site. All commercial insulin formulations contain insulin phenolic preservatives (IPPs) designed to ensure insulin protein stability and prolong shelf-life. However, our laboratory demonstrated that these preservatives are cytotoxic and induce inflammation. Mature mast cells (MCs) reside in cutaneous tissue and are one of the first responders to an epidermal breach. Upon activation, MCs release proinflammatory and immunomodulatory prepacked mediators that exacerbate these inflammatory reactions. Thus, we hypothesized that once the epidermis is breached, cutaneous MCs are triggered inciting the inflammatory response to IPP-induced inflammation. This hypothesis was pursued utilizing our modified in vivo mouse air pouch model, including a c-kit dependent (C57BL/6J-kitW-sh/W-sh) and a c-kit independent (Cpa3-Cre; Mcl-1fl/fl) MC-deficient mouse model. Leukocytes were quantified in the mouse air pouch lavage fluid following flow cytometry analysis for IPP infusion under three different states, insulin-containing phenolic preservatives (Humalog®), insulin preservatives alone, and normal saline as a control. The air pouch wall was assessed using histopathological evaluations. Flow cytometry analysis demonstrated a statistically significant difference in inflammatory cell recruitment for both MC-deficient mouse models when compared to the control strain including infused control saline. Significantly less inflammation was observed at the site of infusion for the MC-deficient strains compared to the control strain. Overall, concordant results were obtained in both mouse types, C57Bl6-kitW-sh/W-sh and Cpa3-Cre; Mcl-1fl/fl. These findings in multiple model systems support the conclusion that MCs have important or possible unique roles in IPP-induced inflammation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Computerized insulin infusion protocols have demonstrated higher staff satisfaction, better compliance with protocols, and increased time with glucose in range compared to paper protocols. At University of California San Diego Health (UCSDH), we implemented an insulin infusion computer calculator (IICC) and transitioned it from a web-based platform directly into the electronic medication administration record (eMAR) of our primary electronic health record (EHR). METHODS: This is a retrospective analysis of 6306 adult patients at UCSDH receiving intravenous (IV) insulin infusion from March 7, 2013 to May 30, 2019. We created three periods of the study-(1) the pre-eMAR integration period; (2) the eMAR integration period; and (3) the post-eMAR integration period-and looked at the percentage of readings within goal range (90-150 mg/dL for intensive care unit [ICU], 90-180 mg/dL for non-ICU) in patients with and without hyperglycemic emergencies. As our safety endpoints, we elected to look at incidence of blood glucose (BG) readings

Objective: To compare the rate of neonatal hypoglycemia among newborns delivered by individuals with Type 2 diabetes mellitus (T2DM) in two clinical scenarios: who attempted vaginal delivery vs. had a planned cesarean delivery (CD); who had intrapartum insulin infusion vs. who did not. Methods: This was a retrospective cohort study of individuals with insulin-treated T2DM who had non-anomalous singleton pregnancy and delivered at a single tertiary center (March 2012 and May 2018). Individuals with chronic renal failure, proliferative retinopathy, or major congenital anomalies were excluded. The primary outcome was neonatal hypoglycemia (blood glucose < 40 mg/dl <24 h of age or < 50 mg/dl >24 h of age). Secondary outcomes included neonatal outcomes. Multivariable Poisson regression models with robust error variance were used to examine the association between groups and the primary outcome. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. Results: Of 233 individuals with T2DM, 215 (92.2%) met the inclusion criteria, of whom 95 (44%) attempted vaginal delivery and 120 (56%) had a planned CD. Individuals who labored had a higher gestational age at delivery (36.6 vs. 35.8 weeks, p = .005), and higher blood glucose levels upon admission (125 vs 103, p < .001) compared to those with a planned CD. After adjustment for potential confounders, there was no difference in risk of neonatal hypoglycemia between the groups (41.2 vs 44.1%, aRR 1.05, 95% CI = 0.75-1.45). Among those who attempted vaginal delivery, 34 (35.8%) required insulin infusion. There was no difference in the risk of neonatal hypoglycemia (aRR = 0.79, 95% CI = 0.45-1.37) between newborns delivered by individuals who required insulin infusion and those who did not. Conclusion: Over 40% of newborns delivered by individuals with insulin-dependent T2DM had hypoglycemia; however, there was no significant difference in the risk of hypoglycemia, irrespective of the route of delivery and the use of insulin infusion. [ABSTRACT FROM AUTHOR]

Hyperglycaemia is recognized as a marker of adverse clinical outcomes for hospitalized patients with and without diabetes, including mortality, morbidity, increased length of stay, infections and overall complications. In some cases, intravenous (IV) insulin infusions are the optimal intervention and, to date, these have been compounded in hospital pharmacy departments or, alternatively, at the point of care, when timeliness is a concern or the pharmacy is closed. However, in-house compounding of high-risk medications such as IV insulin poses risks both for patients and institutions. The critical nature of certain high-risk therapies has led to the development of ready-to-administer products to improve the safety, timeliness, efficacy and efficiency of critical infusions. Recently, IV insulin, a high-alert therapy, has been added to the ready-to-use armamentarium. This narrative review explores the expanding indications, risks and opportunities associated with insulin infusions and potential options for improved safety.

Objective: Surgical site infection (SSI) is one of the most serious potential complications post cardiac surgery among patients with diabetes and has a number of adverse health outcomes. The literature shows discrepancies regarding the effect of different glycaemic control protocols on reducing adverse health outcomes including SSIs. The aim of this study was to conduct a systematic review that investigated the effect of the optimal range of tight glycaemic control protocols using a continuous insulin infusion on reducing the incidence of SSIs in adult patients with diabetes undergoing cardiac surgery. Method: A systematic review was conducted following the PRISMA statement and guidelines. Search terms were used to identify research studies published between 2000 and 2019 across five key databases, including CINAHL, Medline, PubMed, Cochrane Database and Google Scholar. Results: A total of 12 studies met the review inclusion criteria. The reviewed literature tended to support the implementation of a tight glycaemic control protocol, particularly in the postoperative phase, that demonstrated fewer potential complications associated with cardiac surgery. On the other hand, the literature also supported the application of a moderate glycaemic control protocol in the intraoperative phase to obtain better glycaemic stability with fewer potential complications among those patients with diabetes undergoing cardiac surgery. Conclusion: This analysis concludes that tight glycaemic control is more effective than moderate glycaemic control intraoperatively in terms of glycaemic stability among patients with diabetes undergoing cardiac surgery. Results also emphasised the importance of time-based protocol implementation to ensure better health outcomes and better quality of care for patients. [ABSTRACT FROM AUTHOR]

Introduction: In critical care setting, insulin infusion rather than subcutaneous insulin is recommended to maintain the blood glucose (BG) level in the target range. We have devised an insulin infusion protocol which requires monitoring of blood glucose and insulin dose adjustment one hourly. In this study, we have studied the efficacy of our insulin infusion protocol (IIP) in terms of bringing and maintaining blood glucose to target range, and its safety in terms of preventing hypoglycemia. Research design and methods: It is a retrospective review of all patients who received insulin infusion from the 1st of July 2017 to the 30th of June 2018. A total of 231 were included and data pertaining to demographic details and related to insulin infusion was documented in a predefined questionnaire. Results: Insulin infusion was continued for a mean duration of 26.3 ± 13.7 h taking 5.7 ± 3.1 h to reach the target BG level < 180 mg/dl. Once the BG was in the target range, 44.3% of blood glucose readings were between 140 and 180 mg/dl, 62.52% of readings were within the safe range, i.e. 110–180 mg/dl while hypoglycemia (< 70 mg/dl) was observed in only 0.44% times with only one episode of severe hypoglycemia (< 40 mg/dl). The 31.65% of BG readings were found to be above the target BG level (> 180 mg/dl) but the mean BG remains 168.95 ± 45.52 within the desired target range. Conclusion: Our insulin infusion protocol not only achieved and maintained the blood glucose in the target range, it is safe with a very low risk of hypoglycemia. [ABSTRACT FROM AUTHOR]

Context: Stress hyperglycemia in critically ill patients has been a matter of debate for years without any conclusive answer till date regarding glucose management and treatment thresholds. Aims: We planned a study with an aim to compare the efficacy of intensive versus conventional insulin therapy in reducing the mortality and morbidity in critically ill patients. The primary objective was to compare mortality between the two groups. The secondary objective was to find out if intensive insulin therapy is better than conventional insulin therapy in terms of various outcomes such as infections and need for inotropes and transfusion requirements. Settings and Design: It was a prospective randomized controlled study. The study population included 100 patients who received mechanical ventilation and admitted to the intensive care department of a tertiary care institute. Subjects and Methods: Patients were randomly assigned to two groups: intensive insulin therapy (IIT) and conventional insulin therapy (CIT) to receive either intensive or conventional insulin therapy. Insulin infusion was started only when blood glucose levels exceeded 200 mg%. Blood glucose levels were maintained between 80 and 110 mg% in the IIG and between 180 and 200 mg% in the CIG. Statistical Analysis Used: The data collected were analyzed separately for both the groups using Student's t-test and Chi-square test. Results: The two groups were comparable in terms of baseline demographic data including age, sex, preadmission diabetic status, and HbA1c at the time of admission. The two groups were not comparable in terms of Acute Physiology and Chronic Health Evaluation-II scores, and the difference between them was statistically significant with higher scores in the conventional group. The primary outcome, that is, mortality, was higher in the CIG with 29 patients (58%) versus 3 (6%) in the IIG (P = 0.02). The secondary outcomes were the measures of morbidity including infections, need for inotropic support, and need for blood transfusions, and these were significantly higher in the conventional group (P < 0.05). Conclusions: We conclude that tight glycemic control significantly lowers mortality and morbidity in critically ill patients, both surgical and medical. These benefits appear with the maintenance of tight blood glucose control of 80–110 mg.dL− 1 and not due to administration of insulin. [ABSTRACT FROM AUTHOR]

Chest pain is a common and high-risk chief complaint in the emergency department. There is an array of cardiac and non--cardiac-related conditions that could lead to this symptom. It is important for the clinician to have a broad perspective when treating patients complaining of chest pain so that dangerous and potentially life-threatening conditions are not overlooked. Here, we present one such cause of chest pain that can be detrimental if the clinician fails to correctly identify the underlying condition. A brief review of hypertriglyceridemia-induced acute pancreatitis is provided, and challenges faced by the treatment team are discussed. [ABSTRACT FROM AUTHOR]

Purpose Of Review: We reviewed the strategies associated with hypoglycemia risk reduction among critically ill non-pregnant adult patients.Recent Findings: Hypoglycemia in the ICU has been associated with increased mortality in a number of studies. Insulin dosing and glucose monitoring rules, response to impending hypoglycemia, use of computerization, and attention to modifiable factors extrinsic to insulin algorithms may affect the risk for hypoglycemia. Recurring use of intravenous (IV) bolus doses of insulin in insulin-resistant cases may reduce reliance upon higher IV infusion rates. In order to reduce the risk for hypoglycemia in the ICU, caregivers should define responses to interruption of continuous carbohydrate exposure, incorporate transitioning strategies upon initiation and interruption of IV insulin, define modifications of antihyperglycemic therapy in the presence of worsening renal function or chronic kidney disease, and anticipate the effects traceable to other medications and substances. Institutional and system-wide quality improvement efforts should assign priority to hypoglycemia prevention. [ABSTRACT FROM AUTHOR]