Improving Patient Outcomes GLYCEMIC CONTROL IN PERI-OPERATIVE PATIENTS UTILIZING INSULIN INFUSION PROTOCOLS

The Problem Hyperglycemia is common in critically ill surgical patients, regardless of whether they had diabetes before hospital admission. Control of blood glucose has been shifting toward progressively tighter glucose control in diabetics, a paradigm shift also reflected in the care of critically ill patients. Elevated blood glucose (BG) is associated with increased mortality in the ICU setting. Hyperglycemia also causes substantial morbidity in critical illness, including increased risk of nosocomial infection, increased infarct size with worsened outcomes in myocardial infarction and ischemic cerebrovascular accident, and increased protein catabolism after burn injury. Hyperglycemia affects immune function Clinicians have also observed that elevated glucose promotes dehydration and inflammation. Post-operative patients are relatively insulin resistant

The Studies Van den Berghe and associates examined whether the control of hyperglycemia in critically ill patients can lead to improved outcomes in a prospective randomized trial. Study patients were admitted to the ICU for mechanical ventilation. Patients were randomly assigned to one of two groups: the first group received intensive insulin therapy with the goal of trying to maintain glucose at between 80 and 110 mg/dL (ie, normoglycemia), while in the conventional treatment arm the goal glucose was kept between 180 and 200 mg/dL. This study showed that intensive insulin control lowered mortality by > 40%. It also showed that there was a decreased requirement for ventilator support. Interestingly, a decreased need for renal replacement therapy was also demonstrated. Control of hyperglycemia also decreased septic episodes in the patients randomized to intensive insulin therapy by > 40%. In totality, these studies make a compelling case that normoglycemia should be the rule rather than the exception in surgical patients in the ICU.

(from Schwartz Principles of Surgery, Diabetes mellitus (DM): decreased insulin production (type I) and/or increased insulin resistance (type II). Insulin: -inhibits hepatic production of glucose - facilitates glucose transportation into cells - inhibits breakdown of fatty acids (thus decreasing ketone formation) - protein synthesis stimulation UNCONTROLLED DM: - reduction in inflammatory response - reduction in angiogenesis - reduction in collagen synthesis

Adapted from: Insulin delivery during surgery in the diabetic patient. Diabetes Care 1982;5(Suppl 1):65–77

Diabetes mellitus and cardiothoracic surgical site infections American Journal of Infectious Control, Volume 33(6), August 2005, p 353–359

Continuous Intravenous Insulin Infusion Reduces the Incidence of Deep Sternal Wound Infection in Diabetic Patients after Cardiac Surgical Procedures. In Annals of Thoracic Surgery 1999; 67: Q4 hour CBG and RISS (goal <200) VS Insulin Infusion utilizing the Portland CII Protocol (goal between ) patients evaluated Result: Significant reduction (2% in RISS patients vs 0.8% in Insulin infusion patients) in major infectious morbidity and its socioeconomic costs

Common concerns about intensive insulin infusion therapy: 1. Cost ( Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients, Crit Care Med 2006; 34:3: ) 1. Cost: A randomized controlled trial in mechanically ventilated patients admitted to a surgical ICU ( Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients, Crit Care Med 2006; 34:3: ) showed that intensive insulin therapy (goal of 80 and 100 mg/dl) significantly reduced hospital costs by reducing morbidity and mortality (vs conventional therapy of 180 and 200 mg/dl). Table 5. Per patient costs of health care resources in [Euro sign] (interquartile range) consumed in the intensive and conventional treatment groups From: Van den Berghe: Crit Care Med, Volume 34(3).March

2. support personnel availability : Intensive insulin infusion therapy initially requires glucose finger sticks (CBG’s) every 1 hour. However, a study performed at Yale University has shown that the target glucose level was reached within about 6 hours. Once the serum glucose level stabilizes, the frequency of CBG’s can be decreased. Also, the protocols are followed by nurses. Thus, less time is spent on getting insulin orders from physicians. 3. Why the goal of mg/dl?: The American Diabetes Association recommends pre-prandial glucose levels between mg/dl. Also, the study mentioned above showed improved morbidity (Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients, Crit Care Med 2006; 34:3: ). 4. Concerns about hypoglycemia : a study at Yale University showed that even with a serum glucose goal of mg/dl, the rate of hypoglycemic events increased from 0.2 to 0.3% in the CTICU and 0.3 to 0.4 %. 2. support personnel availability : Intensive insulin infusion therapy initially requires glucose finger sticks (CBG’s) every 1 hour. However, a study performed at Yale University (Clinical Results of an Updated Insulin Infusion Protocol in Critically Ill Patients Diabetes Spectrum 18: , 2005 ) has shown that the target glucose level was reached within about 6 hours. Once the serum glucose level stabilizes, the frequency of CBG’s can be decreased. Also, the protocols are followed by nurses. Thus, less time is spent on getting insulin orders from physicians. 3. Why the goal of mg/dl?: The American Diabetes Association recommends pre-prandial glucose levels between mg/dl. Also, the study mentioned above showed improved morbidity (Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients, Crit Care Med 2006; 34:3: ). 4. Concerns about hypoglycemia : a study at Yale University showed that even with a serum glucose goal of mg/dl, the rate of hypoglycemic events increased from 0.2 to 0.3% in the CTICU and 0.3 to 0.4 %.

Clinical Results of an Updated Insulin Infusion Protocol in Critically Ill Patients Diabetes Spectrum 18: , 2005 in Cardiothoracic ICU (Old target glucose levels: mg/dl New target glucose levels: mg/dl) (IIP: Insulin Infusion Protocol)

Clinical Results of an Updated Insulin Infusion Protocol in Critically Ill Patients Diabetes Spectrum 18: , 2005 in Medical ICU (Old target glucose levels: mg/dl New target glucose levels: mg/dl) Clinical Results of an Updated Insulin Infusion Protocol in Critically Ill Patients Diabetes Spectrum 18: , 2005 in Medical ICU (Old target glucose levels: mg/dl New target glucose levels: mg/dl)

Implementation of insulin infusion therapy in peri-operative patients 1.Intensive insulin infusion therapy to be available in D1 – D3. 2.Goal serum glucose levels between 80 and 120 mg/dl. 3.Increased awareness of the need for tight glucose control 4.Increased awareness that hyperglycemia occurs in non-diabetic patients