Overview of Glycemic Control in Critical Care: Relating Performance and Clinical Results

Background: Hyperglycemia is prevalent in critical care and tight control can save lives. Current ad-hoc clinical protocols require significant clinical effort and produce highly variable results. Model-based methods can provide tight, patient specific control, while addressing practical clinical difficulties and dynamic patient evolution. However, tight control remains elusive as there is not enough understanding of the relationship between control performance and clinical outcome. Methods: The general problem and performance criteria are defined. The clinical studies performed to date using both ad-hoc titration and model-based methods are reviewed. Studies reporting mortality outcome are analysed in terms of standardized mortality ratio (SMR) and a 95th percentile (±2σ) standard error (SE95%) to enable better comparison across cohorts. Results: Model-based control trials lower blood glucose into a 72–110 mg/dL band within 10 hours, have target accuracy over 90%, produce fewer hypoglycemic episodes, and require no additional clinical intervention. Plotting SMR versus SE95% shows potentially high correlation (r=0.84) between ICU mortality and tightness of control. Summary: Model-based methods provide tighter, more adaptable one method fits all solutions, using methods that enable patient-specific modeling and control. Correlation between tightness of control and clinical outcome suggests that performance metrics, such as time in a relevant glycemic band, may provide better guidelines. Overall, compared to the current one size fits all sliding scale and ad-hoc regimens, patient-specific pharmacodynamic and pharmacokinetic model-based, or one method fits all control, utilizing computational and emerging sensor technologies, offers improved treatment and better potential outcomes when treating hyperglycemia in the highly dynamic critically ill patient.

[1]  C. Sawin Action without benefit. The sliding scale of insulin use. , 1997, Archives of internal medicine.

[2]  Christopher E. Hann,et al.  Comparison of adaptive and sliding-scale glycaemic control in critical care and the impact of nutritional inputs , 2005 .

[3]  L. Fasano,et al.  Severity scores in respiratory intensive care: APACHE II predicted mortality better than SAPS II. , 1995, Respiratory care.

[4]  G. Van den Berghe,et al.  Intensive insulin therapy in the medical ICU. , 2006, The New England journal of medicine.

[5]  J Geoffrey Chase,et al.  Adaptive bolus-based targeted glucose regulation of hyperglycaemia in critical care. , 2005, Medical engineering & physics.

[6]  R. A. Forse,et al.  Hypocaloric total parenteral nutrition: Effectiveness in prevention of hyperglycemia and infectious complications—A randomized clinical trial , 2000, Critical care medicine.

[7]  I. Hirsch,et al.  Should minimal blood glucose variability become the gold standard of glycemic control? , 2005, Journal of diabetes and its complications.

[8]  A. M. J. Woolfson,et al.  Control of blood glucose during nutritional support in Ill patients , 2005, Intensive Care Medicine.

[9]  James D Dziura,et al.  Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. , 2004, Diabetes care.

[10]  James Stephen Krinsley,et al.  Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. , 2004, Mayo Clinic proceedings.

[11]  J Geoffrey Chase,et al.  Targeted glycemic reduction in critical care using closed-loop control. , 2005, Diabetes technology & therapeutics.

[12]  B A Mizock,et al.  Alterations in fuel metabolism in critical illness: hyperglycaemia. , 2001, Best practice & research. Clinical endocrinology & metabolism.

[13]  P. V. van Heerden,et al.  Closed-loop Control of Blood Glucose Levels in Critically Ill Patients , 2002, Anaesthesia and intensive care.

[14]  L. Lind,et al.  Impaired glucose and lipid metabolism seen in intensive care patients is related to severity of illness and survival. , 1994, Clinical intensive care : international journal of critical & coronary care medicine.

[15]  Christopher E. Hann,et al.  Impact of insulin-stimulated glucose removal saturation on dynamic modelling and control of hyperglycaemia , 2005, Int. J. Intell. Syst. Technol. Appl..

[16]  Hyunah Kim,et al.  Association of hyperglycemia and markers of hepatic dysfunction with dextrose infusion rates in Korean patients receiving total parenteral nutrition. , 2003, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[17]  Christopher E. Hann,et al.  Tight Glycaemic Control in Critical Care Using Insulin and Nutrition - the SPRINT Protocol , 2006 .

[18]  H. Gerstein,et al.  Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview , 2000, The Lancet.

[19]  Charles Weissman,et al.  Nutrition in the intensive care unit , 1999, Critical care.

[20]  R. Dickerson,et al.  Hypocaloric enteral tube feeding in critically ill obese patients. , 2002, Nutrition.

[21]  B. Bistrian,et al.  Intensive insulin therapy in critically ill patients. , 2002, The New England journal of medicine.

[22]  S Andreassen,et al.  Model predictive glycaemic regulation in critical illness using insulin and nutrition input: a pilot study. , 2006, Medical engineering & physics.

[23]  John W Devlin,et al.  Effect of low-calorie parenteral nutrition on the incidence and severity of hyperglycemia in surgical patients: A randomized, controlled trial , 2005, Critical care medicine.

[24]  J. Fernández-Real,et al.  Natural antibiotics and insulin sensitivity: the role of bactericidal/permeability-increasing protein. , 2006, Diabetes.

[25]  R. Rizza,et al.  Effects of size, time of day and sequence of meal ingestion on carbohydrate tolerance in normal subjects , 1983, Diabetologia.

[26]  Yu Shyr,et al.  Insulin resistance in critically ill patients with acute renal failure. , 2005, American journal of physiology. Renal physiology.

[27]  Michael N Diringer Improved outcome with aggressive treatment of hyperglycemia , 2005, Neurology.

[28]  F. Chee,et al.  Expert PID control system for blood glucose control in critically ill patients , 2003, IEEE Transactions on Information Technology in Biomedicine.

[29]  Y. Lin,et al.  Protective effect of a recombinant fragment of bactericidal/permeability increasing protein against carbohydrate dyshomeostasis and tumor necrosis factor-alpha elevation in rat endotoxemia. , 1994, Biochemical pharmacology.

[30]  James Stephen Krinsley,et al.  Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. , 2003, Mayo Clinic proceedings.

[31]  Christian Weyer,et al.  High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. , 2002, Diabetes.

[32]  B. Bistrian,et al.  Hyperglycemia and infection: which is the chicken and which is the egg? , 2001, JPEN. Journal of parenteral and enteral nutrition.

[33]  Irl B Hirsch,et al.  Glycemic variability: it's not just about A1C anymore! , 2005, Diabetes technology & therapeutics.

[34]  V. Gracias,et al.  Glycemic control needs a standard reference point. , 2006, Critical care medicine.

[35]  A. Emami,et al.  HYPERGLYCEMIA AND MORTALITY IN CRITICALLY ILL PATIENTS , 2009 .

[36]  Jean-Paul Cristol,et al.  Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. , 2006, JAMA.

[37]  A. Padkin,et al.  Implementing Intensive Insulin Therapy: Development and Audit of the Bath Insulin Protocol , 2004, Anaesthesia and intensive care.

[38]  A. Malhotra,et al.  Stress-induced hyperglycemia. , 2001, Critical care clinics.

[39]  Richard L. Jones,et al.  Cost analysis of intensive glycemic control in critically ill adult patients. , 2006, Chest.

[40]  Iain Mackenzie,et al.  Tight glycaemic control: a survey of intensive care practice in large English hospitals , 2005, Intensive Care Medicine.

[41]  Mathijs Vogelzang,et al.  Design and implementation of GRIP: a computerized glucose control system at a surgical intensive care unit , 2005, BMC Medical Informatics Decis. Mak..

[42]  H. B. Radack Sliding scale insulin use. , 1997, Archives of internal medicine.

[43]  C. Doran,et al.  Modelling and control of hyperglycemia in critical care patients , 2004 .

[44]  G. Van den Berghe,et al.  Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients* , 2006, Critical care medicine.

[45]  Thomas Lotz,et al.  A pilot study of the SPRINT protocol for tight glycemic control in critically Ill patients. , 2006, Diabetes technology & therapeutics.

[46]  William L Clarke,et al.  Quantifying temporal glucose variability in diabetes via continuous glucose monitoring: mathematical methods and clinical application. , 2005, Diabetes technology & therapeutics.

[47]  F. Cerra,et al.  Applied nutrition in ICU patients. A consensus statement of the American College of Chest Physicians. , 1997, Chest.

[48]  R. Dickerson,et al.  Hypocaloric feeding of obese patients in the intensive care unit , 2005, Current opinion in clinical nutrition and metabolic care.

[49]  William C. Cockerham Physicians , 2001, BMJ : British Medical Journal.

[50]  Roman Hovorka,et al.  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 , 2006, Diabetes Care.

[51]  Scott W. Lee,et al.  Intensive versus modified conventional control of blood glucose level in medical intensive care patients: a pilot study. , 2005, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[52]  F. Brancati,et al.  Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. , 1997, Archives of internal medicine.

[53]  F. Chee,et al.  Closed-loop glucose control in critically ill patients using continuous glucose monitoring system (CGMS) in real time , 2003, IEEE Transactions on Information Technology in Biomedicine.

[54]  J. Sleigh,et al.  Time-dependent Error in the APACHE II Scoring System , 1992, Anaesthesia and intensive care.

[55]  Thomas Lotz,et al.  A simple insulin-nutrition protocol for tight glycemic control in critical illness: development and protocol comparison. , 2006, Diabetes technology & therapeutics.

[56]  G. Diette,et al.  Caloric Intake in Medical ICU Patients: Consistency of Care With Guidelines and Relationship to Clinical Outcomes. , 2004, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[57]  S. Finfer,et al.  Postoperative Pain Management following Bilateral Lung Volume Reduction Surgery for Severe Emphysema , 2005, Anaesthesia and intensive care.

[58]  M Schetz,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[59]  Christopher E. Hann,et al.  Tight glucose control in critically ill patients using a specialized insulin-nutrition table , 2005 .

[60]  Sliding scale fallacy. , 1998, Archives of internal medicine.

[61]  Christopher E. Hann,et al.  Model-based glycaemic control in critical care - A review of the state of the possible , 2006, Biomed. Signal Process. Control..

[62]  Michael Brownlee,et al.  Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. , 2006, JAMA.

[63]  J. Patiño,et al.  Hypocaloric Support in the Critically Ill , 1999, World Journal of Surgery.

[64]  A. Thomas,et al.  Implementation of a tight glycaemic control protocol using a web‐based insulin dose calculator , 2005, Anaesthesia.

[65]  B. Pedersen,et al.  Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans. , 2004, American journal of physiology. Endocrinology and metabolism.

[66]  José Manuel Fernández-Real,et al.  CD14 monocyte receptor, involved in the inflammatory cascade, and insulin sensitivity. , 2003, The Journal of clinical endocrinology and metabolism.

[67]  Palle Toft,et al.  Hyperglycaemia and mortality in critically ill patients , 2004, Intensive Care Medicine.

[68]  Thomas Lotz,et al.  PEAK AND RANGE OF BLOOD GLUCOSE ARE ALSO ASSOCIATED WITH ICU MORTALITY: 453 , 2004 .

[69]  S E Kahn,et al.  The effect of insulin dose on the measurement of insulin sensitivity by the minimal model technique. Evidence for saturable insulin transport in humans. , 1996, The Journal of clinical investigation.

[70]  Michael Brownlee,et al.  The Effect of Glucose Variability on the Risk of Microvascular Complications in Type 1 Diabetes , 2007, Diabetes Care.

[71]  Marcus J. Schultz,et al.  Tight glycaemic control: a survey of intensive care practice in the Netherlands , 2006, Intensive Care Medicine.

[72]  Miet Schetz,et al.  Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control* , 2003, Critical care medicine.

[73]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[74]  P. Marik,et al.  Stress-hyperglycemia, insulin and immunomodulation in sepsis , 2004, Intensive Care Medicine.

[75]  A Mari,et al.  Dose-response characteristics of insulin action on glucose metabolism: a non-steady-state approach. , 2000, American journal of physiology. Endocrinology and metabolism.

[76]  T Lotz,et al.  A novel, model-based insulin and nutrition delivery controller for glycemic regulation in critically ill patients. , 2006, Diabetes technology & therapeutics.