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Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.

ABSTRACT: 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.

SUBMITTER: Aljada A

PROVIDER: S-EPMC6566807 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.

Aljada Ahmad A AlGwaiz Ghada Fahad GF AlAyadhi Demah D Masuadi Emad E Zahra Mahmoud M Al-Matar Shahad H SH Al-Bawab Ahmad A Tamimi Waleed W Jawdat Dunia D Al-Dawood Abdulaziz A Sakkijha Maram H MH Sadat Musharaf M Arabi Yaseen M YM

Nutrients 20190430 5

<h4>Purpose</h4>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.<h4>Methodology</h4>This was a substudy of a 2 × 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients ...[more]

PMID: 31052277

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Project description:BackgroundHyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU).MethodsWe conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation - Survival Using Glucose Algorithm Regulation) study.ResultsWe included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level < or = 6.1 mmol/L v. < or = 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia.InterpretationIntensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.

Project description:OBJECTIVES:Intensive insulin therapy for tight glycemic control in critically ill surgical patients has been shown to reduce mortality; however, intensive insulin therapy is associated with iatrogenic hypoglycemia and increased variability of blood glucose levels. The incretin glucagon-like peptide-1 (7-36) amide is both insulinotropic and insulinomimetic and has been suggested as an adjunct to improve glycemic control in critically ill patients. We hypothesized that the addition of continuous infusion of glucagon-like peptide-1 to intensive insulin therapy would result in better glucose control, reduced requirement of exogenous insulin administration, and fewer hypoglycemic events. DESIGN:Prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING:Surgical or burn ICU. PATIENTS:Eighteen patients who required intensive insulin therapy. INTERVENTIONS:A 72-hour continuous infusion of either glucagon-like peptide-1 (1.5 pmol/kg/min) or normal saline plus intensive insulin therapy. MEASUREMENTS AND MAIN RESULTS:The glucagon-like peptide-1 cohort (n = 9) and saline cohort (n = 9) were similar in age, Acute Physiology and Chronic Health Evaluation score, and history of diabetes. Blood glucose levels in the glucagon-like peptide-1 group were better controlled with much less variability. The coefficient of variation of blood glucose ranged from 7.2% to 30.4% in the glucagon-like peptide-1 group and from 19.8% to 56.8% in saline group. The mean blood glucose coefficient of variation for the glucagon-like peptide-1 and saline groups was 18.0% ± 2.7% and 30.3% ± 4.0% (p = 0.010), respectively. The 72-hour average insulin infusion rates were 3.37 ± 0.61 and 4.57 ± 1.18 U/hr (p = not significant). The incidents of hypoglycemia (? 2.78 mmol/L) in both groups were low (one in the glucagon-like peptide-1 group, three in the saline group). CONCLUSIONS:Glucagon-like peptide-1 (7-36) amide is a safe and efficacious form of adjunct therapy in patients with hyperglycemia in the surgical ICU setting. Improved stability of blood glucose is a favorable outcome, which enhances the safety of intensive insulin therapy. Larger studies of this potentially valuable therapy for glycemic control in the ICU are justified.

Project description:IntroductionClinicians and specialty societies often emphasize the potential importance of natural light for quality care of critically ill patients, but few studies have examined patient outcomes associated with exposure to natural light. We hypothesized that receiving care in an intensive care unit (ICU) room with a window might improve outcomes for critically ill patients with acute brain injury.MethodsThis was a secondary analysis of a prospective cohort study. Seven ICU rooms had windows, and five ICU rooms did not. Admission to a room was based solely on availability.We analyzed data from 789 patients with subarachnoid hemorrhage (SAH) admitted to the neurological ICU at our hospital from August 1997 to April 2006. Patient information was recorded prospectively at the time of admission, and patients were followed up to 1 year to assess mortality and functional status, stratified by whether care was received in an ICU room with a window.ResultsOf 789 SAH patients, 455 (57.7%) received care in a window room and 334 (42.3%) received care in a nonwindow room. The two groups were balanced with regard to all patient and clinical characteristics. There was no statistical difference in modified Rankin Scale (mRS) score at hospital discharge, 3 months or 1 year (44.8% with mRS scores of 0 to 3 with window rooms at hospital discharge versus 47.2% with the same scores in nonwindow rooms at hospital discharge; adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 0.67 to 1.50, P = 0.98; 62.7% versus 63.8% at 3 months, aOR 0.85, 95% CI 0.58 to 1.26, P = 0.42; 73.6% versus 72.5% at 1 year, aOR 0.78, 95% CI 0.51 to 1.19, P = 0.25). There were also no differences in any secondary outcomes, including length of mechanical ventilation, time until the patient was able to follow commands in the ICU, need for percutaneous gastrostomy tube or tracheotomy, ICU and hospital length of stay, and hospital, 3-month and 1-year mortality.ConclusionsThe presence of a window in an ICU room did not improve outcomes for critically ill patients with SAH admitted to the ICU. Further studies are needed to determine whether other groups of critically ill patients, particularly those without acute brain injury, derive benefit from natural light.

Project description:BACKGROUND:Observational and interventional studies in patients with both acute medical conditions and long-standing diabetes have shown that improved blood glucose control confers a survival advantage or reduces complication rates. Policies of "tight" glycaemic control were rapidly adopted by many general intensive care units (ICUs) worldwide in the mid 00's, even though the results of the studies were not generalizable to mixed medical/surgical ICUs with different intravenous feeding policies. OBJECTIVE:The primary objective of the study is to assess the safety of mandatory insulin infusion in critically ill patients in a general ICU setting. METHODS:This protocol summarizes the rationale and design of a randomized, controlled, single-center trial investigating the effect of mandatory insulin therapy versus usual care insulin therapy for those patients admitted for a stay of longer than 48 hours. In total, 109 critically ill adults predicted to stay in intensive care for longer than 48 hours consented. The primary outcome is to determine the safety of mandatory insulin therapy in critically ill patients using the number of episodes of hypoglycaemia and hypokalaemia per unit length of stay in intensive care. Secondary outcomes include the duration of mechanical ventilation, duration of ICU and hospital stay, hospital mortality, and measures of renal, hepatic, and haematological dysfunction. RESULTS:The project was funded in 2005 and enrolment was completed 2007. Data analysis is currently underway and the first results are expected to be submitted for publication in 2018. CONCLUSIONS:This protocol for a randomized controlled trial investigating the effect of mandatory insulin therapy should provide an answer to a key question for the management of patients in the ICU and ultimately improving outcome. TRIAL REGISTRATION:International Standard Randomized Controlled Trial Number ISRCTN00550641; http://www.isrctn.com/ISRCTN00550641 (Archived at WebCite: http://www.webcitation.org/6xk8NXxNv).

Dataset Information

Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.

Publications

Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.

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