Comparative Trial Between 3 Types of Insulin Infusion Protocols
Condition: Hyperglycemia
MeSH terms: Hyperglycemia
Study type: Interventional

Summary: 
      Increasing evidence from observational studies in hospitalized patients with and without
      diabetes indicates that hyperglycemia is a predictor of poor outcome. Over the short-term,
      hyperglycemia can adversely affects fluid balance (through glycosuria and dehydration),
      impairs immunologic response to infection, and promotes inflammation and endothelial
      dysfunction. Blood glucose control with intensive insulin therapy in patients with acute
      critical illness reduces the risk of multiorgan failure and systemic infections, and
      decreases short- and long-term mortality .

      - Hypotheses: we hypothesize that management of inpatient hyperglycemia with a
      computer-guided intravenous infusion protocol (Glucommander) will facilitate a smoother
      glycemic control with a lower rate of hypoglycemic events than treatment following a standard
      insulin infusion algorithm or a simple calculated infusion protocol in critically ill
      patients in the medical and surgical ICU.
    

Detailed description: 
      I. RESEARCH OBJECTIVES AND SPECIFIC AIMS

      A. Introduction:

      Increasing evidence from observational studies in hospitalized patients with and without
      diabetes indicates that hyperglycemia is a predictor of poor outcome. Over the short-term,
      hyperglycemia can adversely affects fluid balance (through glycosuria and dehydration),
      impairs immunologic response to infection, and promotes inflammation and endothelial
      dysfunction. Blood glucose control with intensive insulin therapy in patients with acute
      critical illness reduces the risk of multiorgan failure and systemic infections, and
      decreases short- and long-term mortality .

      The use of intravenous insulin infusion is the preferred route of insulin administration for
      the management of diabetic subjects with diabetic ketoacidosis and nonketotic hyperosmolar
      state, intraoperative and postoperative care, the postoperative period following heart
      surgery and organ transplantation, acute myocardial infarction, stroke, and critical care
      illness. Some of these settings may be characterized by, or associated with, severe or
      rapidly changing insulin requirements, generalized patient edema, impaired perfusion of
      subcutaneous sites, requirement for pressor support, and/or use of total parenteral
      nutrition. In these settings, the intravenous route for insulin administration has been
      considered superior to the subcutaneous injection of split-mixed regimen of intermediate and
      regular insulin with respect to rapidity of effect in controlling hyperglycemia, overall
      ability to achieve glycemic control, and most importantly, preventing hypoglycemic episodes.
      Recently, several insulin infusion protocols have been reported in the literature . In
      general, orders to "titrate drip" are given to achieve a target blood glucose range using an
      established algorithm or by the application of mathematical rules by nursing staff. These
      algorithms and formulas, however, may be confusing and difficult to follow and may increase
      the risk of dosing errors. To facilitate patient care, insulin algorithms could be placed on
      a computer and used at the patient bedside to direct the nursing staff administering the
      intravenous insulin. The Glucommander is one such computer-derived insulin infusion protocol
      which has been used successfully in over 5,802 patients with diabetes between 1984 and 1998.

      B. Hypotheses: we hypothesize that management of inpatient hyperglycemia with a
      computer-guided intravenous infusion protocol (Glucommander) will facilitate a smoother
      glycemic control with a lower rate of hypoglycemic events than treatment following a standard
      insulin infusion algorithm or a simple calculated infusion protocol in critically ill
      patients in the medical and surgical ICU.

      C. Specific Aim: to determine differences in glycemic control between treatment with
      computer-guided intravenous infusion protocol (Glucommander), a standard insulin infusion
      algorithm and a simple calculated infusion protocol in critically ill patients in the medical
      and surgical ICU.

      II. BACKGROUND AND CURRENT STATUS OF WORK IN THE FIELD.

      The result of several observational and interventional studies indicate that hyperglycemia is
      associated with poor hospital outcomes including prolonged hospital stay, infections,
      disability after hospital discharge, and death , and that improvement in outcomes can be
      achieved with improved glycemic control in patients with critical and surgical illness.
      Although there are still no proven mechanisms to explain the detrimental effects of
      hyperglycemia, there are increasing efforts worldwide to improve and maintain strict glycemic
      control in subjects with critical illness.

      In 2001, a large prospective, randomized controlled trial from Leuven, showed that near
      normalization of blood glucose levels using an intensive insulin protocol improved clinical
      outcomes in patients admitted to a surgical intensive care area . In that study, insulin
      administration to maintain blood glucose levels between 80-110 mg/dl, reduced ICU mortality
      by 34%, and reduced the risk of multiorgan failure, systemic infection, incidence of acute
      renal failure, and the need for blood transfusions and prolonged mechanical ventilatory
      support. Interventional studies in the setting of acute coronary events have shown that
      intensive insulin therapy resulted in decreased short- and long-term mortality. Similarly,
      attainment of targeted glucose control in the setting of cardiac surgery is associated with
      reduced mortality and with a significant reduction in deep sternal wound infections.
      Similarly, in the setting of acute neurological illness, stroke, and head injury extensive
      observational and interventional studies indicates that hyperglycemia is associated with
      increased mortality and with diminished neurological recovery . Based in these observational
      and interventional studies, aggressive control of blood glucose is recommended in patients
      with critical illness. A recent position statement of the American Association of Clinical
      Endocrinologists recommended glycemic targets for hospitalized patients in the intensive care
      unit between 80 - 110 mg/dL.

      The American College of Endocrinology position statement supports the following indications
      for intravenous insulin therapy in hospitalized patients with diabetes:

        -  Prolonged fasting (> 12 hours) in type 1 diabetes

        -  Critical illness

        -  Before major surgical procedures

        -  After organ transplantation

        -  Diabetic ketoacidosis

        -  Total parenteral nutrition therapy

        -  Labor and delivery

        -  Myocardial infarction

        -  Other illnesses requiring prompt glucose control.

      Institutions around the world use a variety of insulin infusion algorithms that can be
      implemented by nursing staff. These algorithms facilitate communication between physicians
      and nurses, achieve correction of hyperglycemia in a timely manner, provide a method to
      determine the insulin infusion rate required to maintain blood sugars within a defined target
      range, include a rule for making temporary corrective increments or decrements of insulin
      infusion rate without under- or overcompensation, and allow for adjustment of the maintenance
      rate as patient insulin sensitivity or carbohydrate intake changes. In most insulin infusion
      protocols, orders to "titrate drip" are given to achieve a target blood glucose range using
      an established algorithm or by the application of mathematical rules by nursing staff. These
      algorithms may be confusing and difficult to follow which may increase the risk of errors.

      To facilitate patient care, Drs. Davidson and Steed developed the Glucommander in 1984, a
      computer based system for glycemic control in hospitalized patients. This computer-guided
      insulin infusion system directs the administration of intravenous insulin in response to
      blood glucose measurement at the patient's bedside. Prior to starting the insulin infusion,
      the physician must specify the following parameters: the low end and high end of the target
      range for blood glucose, an initial factor or multiplier, and the maximum time interval
      between blood glucose measurements. During the infusion, the nurse enters blood glucose
      levels and the computer recommends the insulin infusion rate and a time to check the next
      blood glucose testing. The starting insulin infusion follows the formula: insulin / hour =
      multiplier x (BG - 60). The "multiplier" is a parameter that is automatically adjusted based
      on the glucose pattern and response to insulin. For most adults, the initial multiplier is
      0.02. The Glucommander is programmed to adjust the multiplier upwards or downwards if blood
      glucose levels are above or below target levels.

      This study will compare three methods of comparing how glucose is regulated with IV insulin.
      The first method uses a sliding scale of insulin based on glucoses drawn at set intervals.
      The second method uses an algorithm that uses the glucose drawn at a set interval and also
      how much that glucose changed from the last time the glucose was drawn to adjust the amount
      of insulin to be given. The algorithm takes into count how fast the glucose is changing and
      also how far the glucose is from the expected values to improve the accuracy of the amount of
      insulin to be given. The glucocommander is a handheld based algorithm that again takes in how
      fast the glucose has changed and how far the glucose is from where you want to be and adds
      another layer in that it tells the nurse when to draw the next glucose so that if the glucose
      is very far away from the expected value drawing glucose in a shorter time period will help
      get to the expected glucose faster. The comparison is does the method reach the expected
      glucose faster and how often is the glucose going to be to low. Methods that improve the way
      to get the glucose to the expected value are not better for the patient if they increase the
      chance of hypoglycemia. This study will compare three methods of regulating glucose with
      insulin.
    

Intervention name(s): Glucommander-Guided Intravenous Insulin Infusion; Standard Intravenous Insulin Infusion; Simple Calculated Intravenous Insulin Infusion
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): Glucommander-Guided Intravenous Insulin Infusion.
Prepare IV Insulin Drip: 250 units of glulisine (Apidra®) insulin with 250 ml NS (1.0 unit/ml). Piggyback insulin drip into IV fluids.
During the infusion, enter glucose levels into the Glucommander and follow recommendations regarding infusion rate and time to measure next blood glucose levels.; Standard Intravenous Insulin Infusion Standard Intravenous Insulin Infusion in the ICU setting Prepare IV Insulin Drip: 250 units of glulisine (Apidra®) insulin with 250 ml NS (1.0 unit/ml). Piggyback insulin drip into IV fluids.
Algorithm 1: Start here for most patients. Algorithm 2: For patients not controlled with Algorithm 1, or receiving glucocorticoids, or patient with diabetes receiving >80 units/day of insulin as an outpatient.
Algorithm 3: For patients not controlled on Algorithm 2.No Patients Start Here.; If the patient was on insulin prior to this admission, 1/2 of the total insulin dose divided by 24 will be the initial insulin infusion rate. The amount of insulin given will be dependant upon blood sugar levels ( BG levels 80-120= 0.5 units/hr, 121-160=1.0 units/hr, 161-200= 2.0 units/hr, 201-240= 3.0 units/hr, 241-280= 4.0 units/hr, 281-320= 5.0 units/hr, 321-360=6.0 units, 361-400= 7.0 units, greater than 400= 8.0 units.
Other intervention name(s): Computer controlled Algorithm for insulin administration; Algorithm controlled insulin administration; Simple sliding scale for insulin administration
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Glycemic Control; Intravenous Infusion; Standard Insulin infusion algorithm; Infusion; Critically Ill