Design and rationale of Heart and Lung Failure – Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children

ObjectivesTest whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range.DesignMulti-center randomized clinical trial.SettingPediatric ICUs at 35 academic hospitals.PatientsChildren aged 2 weeks to 17 years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients.InterventionsPatients receive intravenous insulin titrated to either 80–110 mg/dL (4.4–6.1 mmol/L) or 150–180 mg/dL (8.3–10.0 mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28 days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk.Measurements and main resultsThe primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test.ConclusionsThis trial tests whether hyperglycemic critically ill children randomized to 80–110 mg/dL benefit more than those randomized to 150–180 mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control.     

Time in blood glucose range 70 to 140?mg/dl >80% is strongly associated with increased survival in non-diabetic critically ill adults

IntroductionHyperglycemia, hypoglycemia and increased glucose variability are independently associated with increased risk of death in critically ill adults. The relationship between time in targeted blood glucose range (TIR) and mortality is not well described and may be a factor that has confounded the results of the major interventional trials of intensive insulin therapy.MethodsWe conducted a retrospective analysis of prospectively collected data involving 3,297 patients with intensive care unit (ICU) lengths of stay (LOS) of ≥1.0 day who were admitted between 1 January 2009 and 31 December 2013 to a single mixed medical-surgical ICU. We investigated the relationship between TIR 70 to 140 mg/dl with mortality and compared outcomes of non-diabetics (NON) and individuals with diabetes mellitus (DM), including stratifying by TIR above (TIR-hi) and below (TIR-lo) the median value for the NON and DM groups.ResultsThere were 85,799 blood glucose (BG) values for the NON group and 32,651 for the DM group, and we found that 75.5% and 54.8%, respectively, were between 70 and 140 (P <0.0001). The median (interquartile range) TIR (%) values for the NON and DM groups were 80.6% (61.4% to 94.0%) and 55.0% (35.5% to 71.1%), respectively (P <0.0001). For the NON group, mortality was 8.47% and 15.71% for TIR-hi and TIR-lo, respectively (P <0.0001). For the DM group, mortality was 16.09% and 14.44% for TIR-hi and TIR-lo, respectively (P = NS). We observed similar relationships for the NON group when we stratified by ICU LOS or severity of illness, especially in the most severely ill patients. There was a cumulative interaction of indices of hypoglycemia, hyperglycemia or glucose variability with TIR. Multivariable analysis demonstrated, for the NON group, that TIR-hi was independently associated with increased survival (P =0.0019). For the NON group, the observed-to-expected mortality ratios for TIR-hi and TIR-lo, based on Acute Physiology and Chronic Health Evaluation IV methodology, were 0.53 and 0.78, respectively. In contrast, among those in the DM group, there was no clear relationship between TIR 70 to 140 mg/dl and survival.ConclusionsIndependently of ICU LOS and severity of illness, TIR 70 to 140 mg/dl >80% is strongly associated with survival in critically ill patients without diabetes. These findings have implications for the design of clinical protocols for glycemic control in critically ill patients as well for the design of future interventional trials of intensive insulin therapy.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0908-7) contains supplementary material, which is available to authorized users.     

危重病患者抢救中胰岛素强化治疗的探讨

目的观察胰岛素强化治疗能否改善重症监护室（ICU）危重患者的预后。方法将116例危重患者随机分为传统治疗组（CT组）和胰岛素强化治疗组（IT组），每4h监测1次床旁血糖。当CT组血糖＞11．9mmol／L时，皮下注射中性可溶性胰岛素控制血糖在10．0～11．1mmol／L；当IT组血糖＞6．1mmol／L时，皮下注射胰岛素控制血糖在4．4～6．1mmol／L。记录患者ICU住院时间、使用呼吸机时间、气管插管或气管套管留置时间、每日早6时平均血糖、每日提供的平均热量、每日胰岛素用量、每日简化治疗干预评分系统-28（TISS-28）评分、人白细胞DR抗原（HLA—DR）、CD4^＋／CD8^＋，死亡、低血糖、肾功能损害（血肌酐＞221／μmol／L）和高胆红素血症（总胆红素＞34．2μmol／L）、输红细胞及发热（口温＞38．5℃）例数。结果CT组病死率（44．83％）远远高于IT组（12．07％），差异有显著性（P＜O．01）；患者ICU住院时间、使用呼吸机时间、气管插管留置时间、每日早6时平均血糖、每日TISS-28评分均明显高于IT组（P＜0．05或P＜0．01）；每日胰岛素用量、HLADR、CD4^＋／CD8^＋均明显低于IT组（P＜0．05或P＜0．01）。两组并发症比较，CT组患者发生肾功能损害、输注红细胞及发热例数均明显高于IT组（P均＜0．01）。结论胰岛素强化治疗控制危重患者血糖在4．4～6．1mmol／L水平确能降低患者的病死率。     

Intensive insulin therapy: enhanced Model Predictive Control algorithm versus standard care

Objective  To investigate the effectiveness of an enhanced software Model Predictive Control (eMPC) algorithm for intravenous insulin infusion, targeted at tight glucose control in critically ill patients, over 72 h, in two intensive care units with different management protocols. Design  Comparison with standard care in a two center open randomized clinical trial. Setting  Two adult intensive care units in University Hospitals. Patients and participants  Thirty-four critically ill patients with hyperglycaemia (glucose >120 mg/dL) or already receiving insulin infusion. Interventions  Patients were randomized, within each ICU, to intravenous insulin infusion advised by eMPC algorithm or the ICU’s standard insulin infusion administration regimen. Measurements and results  Arterial glucose concentration was measured at study entry and when advised by eMPC or measured as part of standard care. Time-weighted average glucose concentrations in patients receiving eMPC advised insulin infusions were similar [104 mg/dL (5.8 mmol/L)] in both ICUs. eMPC advised glucose measurement interval was significantly different between ICUs (1.1 vs. 1.8 h, P < 0.01). The standard care insulin algorithms resulted in significantly different time-weighted average glucose concentrations between ICUs [128 vs. 99 mg/dL (7.1 vs. 5.5 mmol/L), P < 0.01]. Conclusions  In this feasibility study the eMPC algorithm provided similar, effective and safe tight glucose control over 72 h in critically ill patients in two different ICUs. Further development is required to reduce glucose sampling interval while maintaining a low risk of hypoglycaemia. An erratum to this article can be found at     

Association of early-onset constipation and diarrhoea with patient outcomes in critically ill ventilated patients: A retrospective observational cohort study

BackgroundConstipation and diarrhoea are closely related, but few studies have examined them simultaneously.ObjectivesThe purpose of this study was to describe patient defecation status after intensive care unit (ICU) admission and determine the association between early-onset constipation and diarrhoea following ICU admission with outcomes for critically ill ventilated patients.MethodsPatients ventilated for ≥48 h in an ICU were retrospectively investigated, and their defecation status was assessed during the first week after admission. Early-onset constipation and diarrhoea were defined as onset during the first week of ICU admission. The patients were divided into three groups—normal defecation, constipation, and diarrhoea—and multiple comparisons were performed using the Kruskal–Wallis test and the Mann–Whitney U test with Bonferroni adjustment. Additionally, multivariable analysis was performed for mortality and length of stay using the linear and logistic regression models.ResultsOf the 85 critically ill ventilated patients, 47 (55%) experienced early-onset constipation and 12 (14%) experienced early-onset diarrhoea. Patients with normal defecation and diarrhoea increased from the 4th and 5th day of ICU admission. Early-onset diarrhoea was significantly associated with the length of ICU stay (B = 7.534, 95% confidence interval: 0.116–14.951).ConclusionsEarly-onset constipation and diarrhoea were common in critically ill ventilated patients, and early-onset diarrhoea was associated with the length of ICU stay.     

Temperature control in critically ill patients with fever: A meta-analysis of randomized controlled trials

PurposeFever is frequently encountered in ICU. It is unclear if targeted temperature control is beneficial in critically ill patients with suspected or confirmed infection. We conducted a systemic review and meta-analysis to answer this question.MethodsWe systematically reviewed major databases before January 2020 to identify randomized controlled trials (RCTs) that compared antipyretic with placebo for temperature control in non-neurocritical ill adult patients with suspected or confirmed infection. Outcomes of interest were 28-day mortality, temperature level, hospital mortality, length of stay, shock reversal, and patient comfort.Result13 RCTs enrolling 1963 patients were included. No difference in 28-day mortality between antipyretic compared with placebo (risk ratio [RR] 1.03; 95% CI 0.79–1.35). Lower temperature levels were achieved in the antipyretic group (MD [mean difference] -0.41; 95% CI -0.66 to −0.16). Antipyretic use did not affect the risk of hospital mortality (RR 0.97; 95% CI 0.73–1.30), ICU length of stay (MD -0.07; 95% CI -0.70 to 0.56), or shock reversal (RR 1.11; 95% CI 0.76–1.62).ConclusionAntipyretic therapy effectively reduces temperature in non-neurocritical ill patients but does not reduce mortality or impact other outcomes.     

Intensive insulin therapy for critically ill patients

OBJECTIVE: To evaluate the clinical outcomes of glycemic control of intensive insulin therapy and recommend its place in the management of critically ill patients. DATA SOURCES: Searches of MEDLINE (1966-March 2004) and Cochrane Library, as well as an extensive manual review of abstracts were performed using the key search terms hyperglycemia, insulin, intensive care unit, critically ill, outcomes, and guidelines and algorithms. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and deemed relevant if they included and assessed clinical outcomes. DATA SYNTHESIS: Mortality among patients with prolonged critical illness exceeds 20%, and most deaths are attributable to sepsis and multisystem organ failure. Hyperglycemia is common in critically ill patients, even in those with no history of diabetes mellitus. Maintaining normoglycemia with insulin in critically ill patients has been shown to improve neurologic, cardiovascular, and infectious outcomes. Most importantly, morbidity and mortality are reduced with aggressive insulin therapy. This information can be implemented into protocols to maintain strict control of glucose. CONCLUSIONS: Use of insulin protocols in critically ill patients improves blood glucose control and reduces morbidity and mortality in critically ill populations. Glucose levels in critically ill patients should be controlled through implementation of insulin protocols with the goal to achieve normoglycemia, regardless of a history of diabetes. Frequent monitoring is imperative to avoid hypoglycemia.     

Lower mean phosphate independently predicts mortality in critically ill patients: Results from a prospective cohort study

PurposeTo evaluate lower mean phosphate as a prognostic tool in critically ill patients.MethodsThis is a prospective single-center cohort study including adult patients (> 18 years) with a length of intensive care unit (ICU) stay of at least 24 h. Phosphatemia was evaluated within 1 h of ICU admission and once daily. Mean phosphate, calculated by the simple arithmetic mean of daily phosphate measurements, was proposed and tested. Standard severity scores were applied. Multivariate and survival analyses were performed.ResultsA total of 317 patients were included, of whom 111 (35%) presented hypophosphatemia. Hypophosphatemia associated with surgical conditions, nutritional therapy, hypovitaminosis D, hyperparathyroidism, mechanical ventilation (need and duration), and ICU and hospital length of stay were evaluated. Admission APACHE II and SOFA (ICU days 1, 3, and 7) scores and ICU and in-hospital mortality were greater in the hypophosphatemia group than control group. Higher APACHE II (RR: 1.1; 95%CI: 1.01–1.2; p = 0.045) and lower mean phosphate (RR: 0.02; 95%CI: 0.001–0.09; p = 0.044) independently predicted ICU and in-hospital mortality.ConclusionsHypophosphatemia is frequent in the ICU, and was associated with unfavorable outcomes. This study introduces the importance of longitudinal monitoring of phosphate levels, since lower mean phosphate is an independent predictor of mortality in critically ill patients.     

Hyperglycaemia and mortality in critically ill patients

Objective To describe hyperglycaemia as a possible marker of morbidity and mortality in critically ill medical and surgical patients admitted to a multidisciplinary ICU.Design Prospective cohort study.Setting A 13-bed non-cardiac multidisciplinary ICU in a university hospital.Patients and participants Adult patients consecutively admitted to the ICU in a 6-month period. Patients with fewer than 2 days stay in the ICU and patients with known diabetes were excluded.Measurements and results At admission a registration form was filled in including demographic data, first and second day APACHE II scores, infections and daily maximum blood glucose level. In surgical patients, high maximum blood glucose level during the stay in ICU was correlated with increased mortality, morbidity and frequency of infection. In medical patients, we found a non-significant trend towards a correlation between hyperglycaemia and morbidity and mortality, respectively.Conclusions High blood glucose level during the stay in ICU was a marker of increased morbidity and mortality in critically ill surgical patients. In medical patients the same trend was found, but non-significant. The population of patients in the present study are heterogeneous and the results from surgical critically ill patients should not be generalised to medical patients.     

Health technology assessment review: Computerized glucose regulation in the intensive care unit - how to create artificial control

Current care guidelines recommend glucose control (GC) in critically ill patients. To achieve GC, many ICUs have implemented a (nurse-based) protocol on paper. However, such protocols are often complex, time-consuming, and can cause iatrogenic hypoglycemia. Computerized glucose regulation protocols may improve patient safety, efficiency, and nurse compliance. Such computerized clinical decision support systems (Cuss) use more complex logic to provide an insulin infusion rate based on previous blood glucose levels and other parameters. A computerized CDSS for glucose control has the potential to reduce overall workload, reduce the chance of human cognitive failure, and improve glucose control. Several computer-assisted glucose regulation programs have been published recently. In order of increasing complexity, the three main types of algorithms used are computerized flowcharts, Proportional-Integral-Derivative (PID), and Model Predictive Control (MPC). PID is essentially a closed-loop feedback system, whereas MPC models the behavior of glucose and insulin in ICU patients. Although the best approach has not yet been determined, it should be noted that PID controllers are generally thought to be more robust than MPC systems. The computerized Cuss that are most likely to emerge are those that are fully a part of the routine workflow, use patient-specific characteristics and apply variable sampling intervals.     

The effectiveness of systematic pain assessment on critically ill patient outcomes: A randomised controlled trial

BackgroundEvidence suggests that critically ill patients’ pain may still be underestimated. Systematic approaches to pain assessment are of paramount importance for improving patients’ outcomes.ObjectivesTo investigate the effectiveness of a systematic approach to pain assessment on the incidence and intensity of pain and related clinical outcomes in critically ill patients.MethodsRandomized controlled study with consecutive critically ill patients allocated to either a standard care only or a systematic pain assessment group. The Behavioral Pain Scale (BPS) and the Critical Pain Observation Tool (C-POT) were completed twice daily for all participants. In the intervention group, clinicians were notified of pain scores. Linear Mixed Models (LMM) for the longitudinal effect of the intervention were employed.ResultsA total of 117 patients were included (control: n=61; intervention: n2=56). The incidence of pain (C-POT >2) in the intervention group was significantly lower compared to the control group (p < .001). The intervention had a statistically significant effect on pain intensity (BPS, p = 0.01). The average total morphine equivalent dose in the intervention group was higher than in the control group (p = 0.045), as well as the average total dose of propofol (p = 0.027). There were no statistically significant differences in ICU mortality (23.4% vs 19.3%, p=0.38, odds ratio 0.82 [0.337-1.997]) and length of ICU stay (13.5, SD 11.1 vs 13.9, SD 9.5 days, p= 0.47).ConclusionSystematic pain assessment may be associated with a decrease in the intensity and incidence of pain and influence the pharmacological management of pain and sedation of critically ill patients.     

The clinical and paraclinical effectiveness of four-hour infusion vs. half-hour infusion of high-dose ampicillin-sulbactam in treatment of critically ill patients with sepsis or septic shock: An assessor-blinded randomized clinical trial

PurposeThis study was conducted to determine whether critically ill patients admitted to the intensive care unit (ICU) with sepsis and septic shock may benefit from extended infusion of ampicillin/sulbactam compared with those receiving intermittent infusion.Material and methodsThis randomized assessor-blinded clinical trial was conducted in the ICUs of Nemazee and Shahid Rajaee hospital, Shiraz, Iran, from August 2019 to August 2021. The participants randomly received 9 g Ampicillin/Sulbactam every 8 h by either extended (infused over 4 h) or intermittent (infused over 30 min) intravenous infusion if their estimated glomerular filtration rate based on Cockrorft-Gault formula was higher than 60 ml/min.ResultsTotally, 136 patients were enrolled and allocated to the intervention and control groups, each with 68 patients. Clinical cure was significantly higher in the extended group (P = 0.039), but ICU and hospital length of stay did not differ between the groups (P = 0.87 and 0.83, respectively). The ICU (P = 0.031) and hospital (P = 0.037) mortality rates in the extended infusion group were significantly lower than those in the intermittent infusion group.ConclusionThese data should be replicated in larger clinical trials before providing any recommendation in favor of this method of administration in clinical practice.     

Glycemic control in critically ill patients

Hyperglycemia is common in critically ill patients and can be caused by various mechanisms, including nutrition, medications, and insufficient insulin. In the past, hyperglycemia was thought to be an adaptive response to stress, but hyperglycemia is no longer considered a benign condition in patients with critical illnesses. Indeed, hyperglycemia can increase morbidity and mortality in critically ill patients. Correction of hyperglycemia may improve clinical outcomes. To date, a definite answer with regard to glucose management in general intensive care unit patients, including treatment thresholds and glucose target is undetermined. Meta-analyses of randomized controlled trials suggested no survival benefit of tight glycemic control and a significantly increased incidence of hypoglycemia. Studies have shown a J- or U-shaped relationship between average glucose values and mortality; maintaining glucose levels between 100 and 150 mg/dL was likely to be associated with the lowest mortality rates. Recent studies have shown glycemic control < 180 mg/dL is not inferior to near-normal glycemia in critically ill patients and is clearly safer. Glycemic variability is also an important aspect of glucose management in the critically ill patients. Higher glycemic variability may increase the mortality rate, even in patients with the same mean glucose level. Decreasing glucose variability is an important issue for glycemic control in critically ill patients. Continuous measurements with automatic closed-loop systems could be considered to ensure that blood glucose levels are controlled within a specific range and with minimal variability.     

Prise en charge de la glycémie du patient en état critique

The importance of the control of glycemia in critically ill patients has been recently highlighted by the report of significant reductions in the mortality and morbidity in patients in whom the insulin therapy aimed at maintaining blood sugar below 6.1 mmol/L. This article attempts to review the underlying mechanisms of stress hyperglycemia, and the results of previous clinical studies that have assessed the effects of hyperglycemia and of its management in various circumstances.Under the influence of inflammatory mediators and counter-regulatory hormones, a resistance to insulin appears and induces an increase in the production of glucose and a decrease in glucose utilization in some insulin-dependent tissues. The presence of hyperglycemia at the time of admission has been associated with an increased susceptibility to infection and with a worse outcome following acute myocardial infarction and stroke.Even though the underlying mechanisms are only partially elucidated, a tight control of glycemia is warranted in most critically ill patients.     

Optimal blood glucose control in severely burned patients: a long way to go,but one step closer

Over the past years there has been a significant decrease in mortality and morbidity in patients suffering from severe burns due to improved burn wound management and approaches in critical care. Survival is no longer the exception, but unfortunately death still occurs. One of the key elements concerning state-of-the-art burn care is blood glucose control and insulin therapy; it is well known that burn-induced hyperglycaemia is associated with adverse clinical outcomes. However, controversy for insulin therapy and tight glycaemic control in critically ill and burn patients exists. The increased incidence of hypoglycaemia is the dominant argument against this treatment, because hypoglycaemia is also associated with an increased risk for death in critically ill patients. Taking all current data together, insulin therapy appears both a friend and a foe in the treatment of ICU patients. In order to overcome the limits of tight glycaemic control resulting from hypoglycaemic episodes, current efforts have been directed towards the development of protocols allowing for implementation of clinically feasible and safe guidelines. Among the strategies addressing this problem are closed loop techniques, which are supported by studies demonstrating their capability of exerting tight glycaemic control without the risk of developing hypoglycaemic episodes. Although closed loop techniques have become readily available, we require further evidence to ensure their safety in various ICU environments, notably in ICUs dealing with burn patients. Nonetheless, it is important to emphasise that glycaemic control and adequate insulin therapy are crucial factors for the final outcome (survival) and require our attention.     

Degree of hyperglycemia independently associates with hospital mortality and length of stay in critically ill,nondiabetic patients: Results from the ANZICS CORE binational registry

PurposeHyperglycemia (HG) in critically ill patients influences clinical outcomes and hospitalization costs. We aimed to describe association of HG with hospital mortality and length of stay in large scale, real-world scenario.MaterialsFrom The Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD) we included 739,152 intensive care unit (ICU) patients admitted during 2007–2016. Hyperglycemia was quatified using midpoint blood glucose level (MBGL). Association with outcomes (hospital mortality and length of stay (LOS)) was tested using multivariable, mixed effects, 2-level hierarchical regression.ResultsDegree of HG (defined using MBGL as a continuous variable) was significantly associated with hospital mortality and longer hospital stay in a dose-dependent fashion. The fourth, third and second MBGL (compared to the first) quartiles were associated with hospital mortality (odds ratio 1.34, 1.05 and 0.97, respectively) and longer hospital stay (1.56, 1.38 and 0.93 days, respectively). These associations were stronger associations in trauma (especially head injury), neurological disease and coma patients. Significant variation across ICUs was observed for all associations.ConclusionsIn this largest study of nondiabetic ICU patients, HG was associated with both study outcomes. This association was differential across ICUs and diagnostic categories.     

Multicentric, randomized, controlled trial to evaluate blood glucose control by the model predictive control algorithm versus routine glucose management protocols in intensive care unit patients

OBJECTIVE: To evaluate a fully automated algorithm for the establishment of tight glycemic control in critically ill patients and to compare the results with different routine glucose management protocols of three intensive care units (ICUs) across Europe (Graz, Prague, and London). RESEARCH DESIGN AND METHODS: Sixty patients undergoing cardiac surgery (age 67 +/- 9 years, BMI 27.7 +/- 4.9 kg/m2, 17 women) with postsurgery blood glucose levels >120 mg/dl (6.7 mmol/l) were investigated in three different ICUs (20 per center). Patients were randomized to either blood glucose management (target range 80-110 mg/dl [4.4-6.1 mmol/l]) by the fully automated model predictive control (MPC) algorithm (n = 30, 10 per center) or implemented routine glucose management protocols (n = 30, 10 per center). In all patients, arterial glucose was measured hourly to describe the glucose profile until the end of the ICU stay but for a maximum period of 48 h. RESULTS: Compared with routine protocols, MPC treatment resulted in a significantly higher percentage of time within the target glycemic range (% median [min-max]: 52 [17-92] vs. 19 [0-71]) over 0-24 h (P < 0.01). Improved glycemic control with MPC treatment was confirmed in patients remaining in the ICU for 48 h (0-24 h: 50 [17-71] vs. 21 [4-67], P < 0.05, and 24-48 h: 65 [38-96] vs. 25 [8-79], P < 0.05, for MPC [n = 16] vs. routine protocol [n = 13], respectively). Two hypoglycemic events (<54 mg/dl [3.0 mmol/l]) were observed with routine protocol treatment. No hypoglycemic event occurred with MPC. CONCLUSIONS: The data suggest that the MPC algorithm is safe and effective in controlling glycemia in critically ill postsurgery patients.     

Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults

Objective Aggressive glycemic control improves mortality and morbidity in critically ill adults, however implementation of such a strategy can be logistically difficult. This study evaluates the efficiency and safety of a nurse-managed insulin protocol in critically ill adults.Design Combined retrospective-prospective before-after cohort study.Setting Twenty-one bed, medical/surgical ICU in a tertiary care hospital.Patients Two cohorts of 50 consecutive ICU patients requiring insulin infusions.Intervention Patients in the control cohort received insulin infusions titrated according to target blood glucose ranges and sliding scales at the physicians discretion. Patients in the interventional cohort received an insulin infusion adjusted using a standardized protocol targeting a blood glucose of 4.5–6.1 mmol/l (81–110 mg/dl).Measurements and main results Efficiency was measured by comparing the time to reach, and the time spent within, the target range between cohorts. Safety was assessed by comparing the incidence of severe hypoglycemia, the frequency of rescue dextrose administration and the cumulative time that the infusion was held for hypoglycemia between cohorts. Patients in the interventional cohort reached their target more rapidly (11.3±7.9 vs 16.4±12.6 h; p=0.028) and maintained their blood glucose within the target range longer (11.5±3.7 vs 7.1±5.0 h/day; p<0.001) than controls. The standardized protocol yielded a four-fold reduction in the incidence of severe hypoglycemia (4 vs 16%; p=0.046) and reduced the median frequency of dextrose rescue therapy (0 [0–0.91] vs 0.17 [0–1.2] episodes/patient per day; p=0.01) as compared to controls.Conclusion Standardization of intensive insulin therapy improves the efficiency and safety of glycemic control in critically ill adults.