Objective To observe the effect of intensive insulin therapy on the critically ill patients with stress hyperglycemia in ICU.Methods One hundred and ten critically ill patients in ICU were randomly divided into two groups,the intensive insulin therapy group(n=55) and control group(n=55).The blood glucose in the intensive insulin therapy group was controlled at 4.4 to 6.1 mmol/L,and the blood glucose in control group was controlled at 10.0 to 11.1 mmol/L.The two groups were observed and compared the days in the ICU,the numbers of patients requiring mechanical ventilation,the days of mechanical ventilation,the incidences of infection in hospital,the days of using antibiotics,Acute Physiology and Chronic Health Evaluation Ⅱ score of the last day in ICU,the morbidity of multiple organ failure,the morbidity of hypoglycemia and mortality.Results All the above indices except morbidity of hypoglycemia were significantly lower in the intensive insulin therapy group than those in control group(P0.05 or P0.01).Conclusion Intensive insulin therapy and keeping blood glucose at 4.4 to 6.1 mmol/L can improve the clinical curative effect and reduce the mortality for the critically ill patients with stress hyperglycemia,

Intensive insulin therapy for the critically ill patients with stress hyperglycemia

Hypoglycemia with intensive insulin therapy after cardiac surgery: predisposing factors and association with mortality.

The difficulty in achieving tight glycemic control (TGC)1,2 in the adult intensive care unit (ICU) is well documented.3,4 We aimed to explore the impact of insulin adsorption onto infusion sets in the laboratory and to assess retrospectively if higher insulin doses are required after syringe changes in practice in the ICU. Adsorption is reported to occur predominantly during the first hour of infusion, after which binding sites are saturated.5 There is greater insulin recovery with faster flow rates and higher insulin concentration.6 The clinical significance of such adsorption in the ICU setting is uncertain.5

In our study—approved by the local ethics committee—adsorption of insulin onto the giving sets used in our adult ICU was analyzed. The infusion set used was a 50 ml polypropylene syringe (BD Plastipak®) and 1.6 ml/200 cm polyethylene (PE) tubing (Cardinal Health, extension set). In the laboratory, the concentration investigated was 1 U/ml of neutral insulin in sodium chloride 0.9%. The concentrations were determined using a high-performance liquid chromatography method with a Jupitor 300, 5 μm C18, 250 mm × 4.6 mm column (Phenomenex), a mobile phase of 30% acetonitrile and 0.1% TFA in water, and ultraviolet detection at 210 nm. Significant insulin adsorption of 10% occurred during the first hour of an infusion when the infusion rate was 1 ml/h (Figure 1). Our experience suggests that this is a common infusion rate used in intensive insulin therapy. No significant adsorption occurred when the infusion rate was 4 ml/h, although a trend could be seen with solution leaving the PE tubing at the beginning of the time period having a lower insulin concentration, which increased with time.



Figure 1.

The mean (± standard error) insulin concentration versus time with an infusion rate of 1 U/h.



The infusion rates used before and after an infusion set change were investigated for 17 ICU patients known to have been managed with a TGC protocol, aiming for glycemia of 4.4–6.1 mmol/liter, to examine any relationship between the duration of usage of the infusion set and the variation in insulin dosing required. These patients were not prescribed drugs known to affect glucose control, such as inotropes and corticosteroids. In the ICU patients, a significantly higher insulin infusion rate was required after an infusion set change when the infusion rate was 1 ml/h or lower. After an infusion set change, the rate was adjusted upward in 76.5% of cases.

In conclusion, we found in the laboratory that less insulin is delivered during the first three hours after an infusion set change, when the infusion rate is 1 ml/h or lower, due to adsorption onto infusion sets. In the ICU, a higher infusion rate was frequently required after an infusion set change when the infusion rate was 1 ml/h or lower. Our results indicate that at low infusion rates, if the syringe and line are not primed, only 90% expected insulin is delivered. The clinical impact of a loss of 0.1 U/h of insulin is questionable, but in practice when syringes were changed, higher rates were frequently required. Further investigation should be undertaken to confirm these findings.

The impact of insulin adsorption onto the infusion sets in the adult intensive care unit.

BACKGROUND Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control. This report describes how IIT can be improved by protocol simplification and removal of glucose supplementation. METHODS A clinical information system established at each bedspace guided staff through the IIT algorithms. Time spent within predefined glycemic ranges was calculated assuming a linear trend between successive measurements. Three groups were investigated retrospectively: IIT1 protocol,(1) an updated IIT2 version, and intuitive nurse dosing of conventional insulin therapy (CIT). RESULTS Fifty consecutive, critically ill patients were included in each study group. Patient characteristics were similar in each group. The frequency of CIT and IIT2 blood glucose measurements were 11.6 and 11.5 measurements per day, respectively, while the IIT1 measurements were more frequent (14.5 measurements per day). The mean proportion of time spent in the target glycemic range (4.4-6.1 mmol/liter) was highest in the IIT2 group (34.9%), as compared to the IIT1 (22.9%) and CIT groups (20.3%) (p <.001). Survival at 28 days was 74.5% for IIT2 (highest), 68% for IIT1, and 48% for CIT (p = .02). There were a similar number of those experiencing a severe hypoglycemic event in each group. CONCLUSIONS IIT protocol optimization was associated with increased glycemic control and improved 28-day survival. The better optimized IIT2 protocol provided tighter control than either the IIT1 or CIT protocol, without increased sampling or incidence of hypoglycemia. The clinical effectiveness of the IIT algorithm appeared to be improved by simplifying the protocol to meet the needs of the critical care unit.

Improvement in glycemic control and outcome corresponding to intensive insulin therapy protocol development.

Objectives To assess the uptake of second-line antihyperglycemic agents among patients with type-2 diabetes mellitus (T2DM) receiving metformin. Design Serial cross-sectional study (2011-2021). Setting Ten US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network. Participants 4.8 million patients with T2DM receiving metformin. Main Outcomes Measures Calendar-year trends in the proportional initiation of second-line antihyperglycemic agents, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors, and sulfonylureas, for each database. We also evaluated the relative drug class-level uptake across cardiovascular risk groups. Results We identified 4.6 million patients with T2DM in US databases, 61,382 from Spain, 32,442 from Germany, 25,173 from the UK, 13,270 from France, 5,580 from Scotland, 4,614 from Hong Kong, and 2,322 from Australia. During 2011-2021, the combined proportional initiation of cardioprotective antihyperglycemic agents, GLP-1 RAs and SGLT2is, increased across all data sources, with the combined initiation of these drugs as second-line agents in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of GLP-1 RAs and SGLT2is increased more significantly among populations without cardiovascular disease compared to those with established cardiovascular disease, without any data source providing evidence of a greater increase in their uptake in the populations with cardiovascular disease. Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycemic agents as second-line treatment for T2DM, their uptake was lower in patients with cardiovascular disease over the last decade. A strategy to ensure medication use concordant with guideline recommendations is essential to improve outcomes of patients with T2DM.

Multinational Patterns of Second-line Anti-hyperglycemic Drug Initiation Across Cardiovascular Risk Groups: A Federated Pharmacoepidemiologic Evaluation in LEGEND-T2DM

Neelam Shah

Papers

Improvement in glycemic control and outcome corresponding to intensive insulin therapy protocol development.

Multinational Patterns of Second-line Anti-hyperglycemic Drug Initiation Across Cardiovascular Risk Groups: A Federated Pharmacoepidemiologic Evaluation in LEGEND-T2DM