&lt;number&gt; Thank you Dr. Ackerman: Distinguished guests and colleagues. It is my honor and privilege to be with you today and take you on a virtual tour of our home, the UMMC, and as we walk through this beautiful atrium, we will take the glass elevator to the seventh floor to bring you a small area in the hospital called the PICU, lovingly know as the mobile trailer home, since we are temporarily housed there until renovations are complete for our new location on the fifth floor. In this huge hospital it occupies a small place. But it is here that we fight life and death battle along with family and patients, to turn life threatening diseases into victories. We see children from newborn to adolescents with meningitis, complex heart problems, MVA, AIDS, life threatening asthma & diabetes, child abuse, suicidal attempts, near drowning and house fires, sickle cell crises to childhood cancer. Children are resilient, they are happy, quiet when they are sick, boisterous as soon as they recover a little bit. They are fighters and teach us how to fight along with them In the next twenty minutes I am going to welcome you guests into our home. Our home is the UMMS, As you make your way though this large house, I am going to take you into our small world on the seventh floor called the PICU It is my honor and privilege to share my thoughts with this group whose backgrounds are varied, yet all of them share the same magnanimous goal in their hearts about the well being of our future, our children To share my work, my plans and my visions come the common
Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000;355:773-778.
l In patients treated for critical illness, it was noted that hyperglycemic patients treated with conventional therapy suffer increased overall mortality and an increased risk of sepsis, acute renal failure and critical illness-related neuropathy (6). l l
Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients.Krinsley JS.Division of Critical Care, The Stamford Hospital, Stamford, Conn 06902, USA. Jkrinsley@stamhealth.orgOBJECTIVE: To investigate the relationship between hyperglycemia and hospital mortality in a heterogeneous group of critically ill patients. PATIENTS AND METHODS: Retrospective data were reviewed for 1826 consecutive patients whose glucose values were obtained during their intensive care unit stay at The Stamford Hospital in Stamford, Conn, between October 1, 1999, and April 4, 2002. RESULTS: Mean and maximum glucose values were significantly higher among nonsurvivors than among survivors for the entire group (P &lt; .001) and for each subgroup except for patients with septic shock. The lowest hospital mortality, 9.6%, occurred among patients with mean glucose values between 80 and 99 mg/dL. Hospital mortality increased progressively as glucose values increased, reaching 42.5% among patients with mean glucose values exceeding 300 mg/dL. Within each of 3 groupings of Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (0-14; 15-24; &gt; or = 25), mean and maximum glucose values were higher among nonsurvivors than among survivors. CONCLUSION: Even a modest degree of hyperglycemia occurring after intensive care unit admission was associated with a substantial increase in hospital mortality in patients with a wide range of medical and surgical diagnoses. Analysis of glucose values added predictive power above that achieved by APACHE II scores alone. These results have important implications for the glycemic management of critically ill patients.
less well-known that intensive glycemic control during labor and delivery also significantly benefits fetal well-being Jovanovich Am J Med 1983;
Malmberg, K., A. Norhammar, et al. (1999). &quot;Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study.&quot; Circulation 99(20): 2626-32. BACKGROUND: The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study addressed prognostic factors and the effects of concomitant treatment and glycometabolic control in diabetic patients with myocardial infarction (AMI). METHODS AND RESULTS: Of 620 diabetic patients with AMI, 306 were randomly assigned to a &gt;/=24-hour insulin-glucose infusion followed by multidose subcutaneous insulin. Three hundred fourteen patients were randomized as controls, receiving routine antidiabetic therapy. Thrombolysis and beta-blockers were administered when possible. Univariate and multivariate statistical analyses were applied to study predictors of long-term mortality. During an average follow-up of 3.4 years (range, 1.6 to 5.6 years), 102 patients (33%) in the intensive insulin group and 138 (44%) in the control group died (P=0. 011). Old age, previous heart failure, diabetes duration, admission blood glucose, and admission Hb AIc were independent predictors of mortality in the total cohort, whereas previous AMI, hypertension, smoking, or female sex did not add independent predictive value. Metabolic control, mirrored by blood glucose and Hb AIc, improved significantly more in patients on intensive insulin treatment than in the control group. beta-Blockers improved survival in control subjects, whereas thrombolysis was most efficient in the intensive insulin group. CONCLUSIONS: Mortality in diabetic patients with AMI is predicted by age, previous heart failure, and severity of the glycometabolic state at admission but not by conventional risk factors or sex. Intensive insulin treatment reduced long-term mortality despite high admission blood glucose and Hb AIc.
&lt;number&gt; van den Berghe, G., P. Wouters, et al. (2001). &quot;Intensive insulin therapy in the critically ill patients.&quot; N Engl J Med 345(19): 1359-67. BACKGROUND: Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. METHODS: We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). RESULTS: At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P&lt;0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. CONCLUSIONS: Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.
Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Furnary AP, Wu Y, Bookin SO.Providence St. Vincent Hospital and Oregon Health and Sciences, University, Portland, Oregon, USA.OBJECTIVE: To describe the main findings of the Portland Diabetic Project, which elucidates the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineates the protective effects of intravenous insulin therapy in reducing those adverse outcomes. RESULTS: In this ongoing 17-year prospective, nonrandomized, interventional study of 4,864 patients with diabetes who underwent an open-heart surgical procedure, we investigated the effects of hyperglycemia, and its subsequent reduction by continuous intravenous insulin (CII) therapy, on in-hospital outcomes. Increasing blood glucose levels were found to be directly associated with increasing rates of death, deep sternal wound infections (DSWI), length of hospital stay (LOS), and hospital cost. In separate multivariate analyses, increasing hyperglycemia was found to be independently predictive of increasing mortality (P&lt;0.0001), DSWI (P = 0.017), and LOS (P&lt;0.002). Conversely, CII therapy, designed to achieve predetermined target blood glucose levels, independently reduced the risks of death and DSWI by 57% and 66%, respectively (P&lt;0.0001 for both). Target blood glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the effect of the CII therapy on improved outcomes. Coronary artery bypass grafting-related mortality (2.5%) and DSWI rates (0.8%) in patients with diabetes were normalized to those of the nondiabetic population by the use of the Portland CII Protocol. CONCLUSION: Perioperative hyperglycemia in patients undergoing a cardiac surgical procedure affects biochemical and physiologic functions, which, in turn, adversely alter mortality, LOS, and infection rates. The Portland CII Protocol is a cost-efficient method that effectively eliminates hyperglycemia and reduces postoperative morbidity and mortality in patients with diabetes undergoing an open-heart operation. CII protocols should be the standard care for glycometabolic control in all patients undergoing cardiac surgical procedures.
Krinsley, J. S. (2004). &quot;Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.&quot; Mayo Clin Proc 79(8): 992-1000. OBJECTIVE: To assess the effect of an intensive glucose management protocol in a heterogeneous population of critically ill adult patients. PATIENTS AND METHODS: This study consisted of 800 consecutive patients admitted after institution of the protocol (treatment group, between February 1, 2003, and January 10, 2004) and 800 patients admitted immediately preceding institution of the protocol (baseline group, between February 23, 2002, and January 31, 2003). The setting was a 14-bed medical-surgical intensive care unit (ICU) in a university-affiliated community teaching hospital. The protocol involved intensive monitoring and treatment to maintain plasma glucose values lower than 140 mg/dL. Continuous intravenous insulin was used if glucose values exceeded 200 mg/dL on 2 successive occasions. RESULTS: The 2 groups of patients were well matched, with similar age, sex, race, prevalence of diabetes mellitus, Acute Physiology and Chronic Health Evaluation II scores, and distribution of diagnoses. After institution of the protocol, the mean glucose value decreased from 152.3 to 130.7 mg/dL (P&lt;.001), marked by a 56.3% reduction in the percentage of glucose values of 200 mg/dL or higher, without a significant change in hypoglycemia. The development of new renal insufficiency decreased 75% (P=-.03), and the number of patients undergoing transfusion of packed red blood cells decreased 18.7% (P=.04). Hospital mortality decreased 29.3% (P=.002), and length of stay in the ICU decreased 10.8% (P=.01). CONCLUSION: The protocol resulted in significantly improved glycemic control and was associated with decreased mortality, organ dysfunction, and length of stay in the ICU in a heterogeneous population of critically ill adult patients. These results support the adoption of this low-cost intervention as a standard of care for critically ill patients.
FROM GARBER REF 12 IN END NOTE hyperglycemia plays an important role in aggravating the inflammatory response, in that overflow of substrates in the mitochondria causes the formation of excess free oxygen radicals and may also alter gene expression to enhance cytokine production
, and lowering inflammatory and prothrombotic mediators (17,18).
While no data exist to guide therapy for intraoperative glycemic management, postoperative data and pathophysiologic reasoning would suggest that improved glycemic control may improve patient outcomes. Until recently no guidelines or position statements regarding inpatient or perioperative glycemic control had been proposed. In December 2003, the American Association of Clinical Endocrinologists &lt;www.aace.com&gt; convened a consensus development conference on inpatient metabolic control. The purpose of the conference was to bring together international thought leaders in glucose management to develop medical guidelines for inpatient glycemic control, including the perioperative period. Implementing such guidelines during the perioperative period would involve anesthesiologists directly in a variety of settings, and while ASA was invited to provide commentary, there was no opportunity to provide input for development of the position statement.The position statement considered intravenous insulin to be indicated for glycemic management in critically ill patients during the perioperative period and labor and delivery and following high-dose glucocorticoid therapy.4 The following guidelines were proposed as upper limits for glycemic targets: ICU patients &lt;110 mg/dl; non-ICU patients &lt;110 mg/dl preprandial, &lt;180 mg/dl maximum; labor and delivery patients &lt;100 mg/dl. The consensus panel members considered 110 mg/dl as the upper limit during the perioperative period.These new guidelines, if accepted and implemented as suggested, would have profound impact on current anesthesiology practice. The guidelines are intended for all patients, not just those with a diagnosis of diabetes. Furthermore, with a blood glucose &gt;110 mg/dl as an indication for insulin therapy, a large percentage of patients would receive insulin therapy during the perioperative period. With obesity increasing in the United States, it would be expected that the population at risk for hyperglycemia would only increase in the coming years.While no data exist to guide therapy for intraoperative glycemic management, postoperative data and pathophysiologic reasoning would suggest that improved glycemic control may improve patient outcomes. Until recently no guidelines or position statements regarding inpatient or perioperative glycemic control had been proposed. In December 2003, the American Association of Clinical Endocrinologists &lt;www.aace.com&gt; convened a consensus development conference on inpatient metabolic control. The purpose of the conference was to bring together international thought leaders in glucose management to develop medical guidelines for inpatient glycemic control, including the perioperative period. Implementing such guidelines during the perioperative period would involve anesthesiologists directly in a variety of settings, and while ASA was invited to provide commentary, there was no opportunity to provide input for development of the position statement.The position statement considered intravenous insulin to be indicated for glycemic management in critically ill patients during the perioperative period and labor and delivery and following high-dose glucocorticoid therapy.4 The following guidelines were proposed as upper limits for glycemic targets: ICU patients &lt;110 mg/dl; non-ICU patients &lt;110 mg/dl preprandial, &lt;180 mg/dl maximum; labor and delivery patients &lt;100 mg/dl. The consensus panel members considered 110 mg/dl as the upper limit during the perioperative period.These new guidelines, if accepted and implemented as suggested, would have profound impact on current anesthesiology practice. The guidelines are intended for all patients, not just those with a diagnosis of diabetes. Furthermore, with a blood glucose &gt;110 mg/dl as an indication for insulin therapy, a large percentage of patients would receive insulin therapy during the perioperative period. With obesity increasing in the United States, it would be expected that the population at risk for hyperglycemia would only increase in the coming years.
Gandhi GY, Nuttall GA, Abel MD, Mullany CJ, Schaff HV, Williams BA, Schrader LM, Rizza RA, McMahon MM.Department of Internal Medicine and Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA. email@example.comOBJECTIVE: To estimate the magnitude of association between intraoperative hyperglycemia and perioperative outcomes in patients who underwent cardiac surgery. PATIENTS AND METHODS: We conducted a retrospective observational study of consecutive adult patients who underwent cardiac surgery between June 10, 2002, and August 30, 2002, at the Mayo Clinic, a tertiary care center in Rochester, Minn. The primary independent variable was the mean intraoperative glucose concentration. The primary end point was a composite of death and infectious (sternal wound, urinary tract, sepsis), neurologic (stroke, coma, delirium), renal (acute renal failure), cardiac (new-onset atrial fibrillation, heart block, cardiac arrest), and pulmonary (prolonged pulmonary ventilation, pneumonia) complications developing within 30 days after cardiac surgery. RESULTS: Among 409 patients who underwent cardiac surgery, those experiencing a primary end point were more likely to be male and older, have diabetes mellitus, undergo coronary artery bypass grafting, and receive insulin during surgery (P&lt; or =.05 for all comparisons). Atrial fibrillation (n=105), prolonged pulmonary ventilation (n=53), delirium (n=22), and urinary tract infection (n=16) were the most common complications. The initial, mean, and maximal intraoperative glucose concentrations were significantly higher in patients experiencing the primary end point (P&lt;.01 for all comparisons). In multivariable analyses, mean and maximal glucose levels remained significantly associated with outcomes after adjusting for potentially confounding variables, including postoperative glucose concentration. Logistic regression analyses indicated that a 20-mg/dL increase in the mean intraoperative glucose level was associated with an increase of more than 30% in outcomes (adjusted odds ratio, 1.34; 95% confidence Interval, 1.10-1.62). CONCLUSION: Intraoperative hyperglycemia is an independent risk factor for complications, including death, after cardiac surgery.
Tight Glycemic Control: Implementation, the key to success
Tight Glycemic Control:
Implementation, the key to success
Vinay Vaidya, MD
-Assistant Professor Pediatrics
-Director, Pediatric Critical Care Fellowship Program
University of Maryland School of Medicine
• How common is Diabetes / Hyperglycemia in
hospitalized patient ?
• Is Hyperglycemia Bad?
• Is Normoglycemia Good?
• What’s the pathophysiologic basis?
• How is Tight Glycemic Control (TGC) achieved ?
• What’s going on in ICU’s at UMMS?
• Challenges in implementing TGC?
• What’s going on in the PICU?
• Anesthesia implications ?
• Future directions?
Diabetes is common in Hospitals
• 9.5% of all hospital discharges, fourth most
common co-morbid diagnosis in all discharges.
• 29% of cardiac surgery patients
• 2-4 fold increase in rates of hospitalizations
• Increases length of stay by 1-3 days
Incidence of Hyperglycemia in
• More than 80 to 90% of ICU patients will
have a blood sugar > 126 mg/dl and
approximately 60% will NOT BE KNOW
• 98.7% of 1548 patients BS > 110 mg/dl
(Van den Berghe study, 2001)
Umpierrez et al J Clin Endocrinol Metab 2002
• 2030 patients on general floor
• Prevalence: 38%
• 10 fold increased mortality (16% vs
1.7%) if BS > 126 mg/dl
• 2 fold Length of Stay
• Higher admission to ICU
• Increased infection risk
Hyperglycemia & Acute MI
Capes et al. Lancet. 2000
• Meta-analysis of 15 studies (BG >110
mg/dL with or without a prior diagnosis of
• increased in-hospital mortality
• Increased CHF
Hyperglycemia in Cardiac
Furnary, Circulation 1999
Zerr, Ann Thorac Surg 1997
• Hyperglycemia associated with
– deep wound infections
– overall infection
• Hyperglycemia, on postop day 1 & 2 =
single most important predictor of
serious infectious complications.
Hyperglycemia & Stroke
Capes et al, Stroke 2001
Kiers et al, J Neuro Neurosurg Psych 1992
• Meta-analysis of 26 studies on stroke: Increased
mortality levels in non-diabetics with
• Stroke survivors: BS range 120-145 mg/dl:
Worse functional recovery.
• Patients with known diabetes and/or newly-
discovered hyperglycemia (>140 mg/dl) more
severe strokes with greater mortality
High BS is Bad, Is Higher Bader?
Krinsley, Mayo Clinic Proceedings, 2003
• 1,826 ICU patients
• direct and proportional correlation with BS
• BS range from < 100 to > 300: Mortality
10% to 43%
• Even modest hyperglycemia associated
with a substantial increase in mortality in
patients with a wide range of medical and
Pregnancy & Hyperglycemia
• It is well-known that pregnancy
complicated by uncontrolled diabetes
results in poor fetal outcomes
Pediatric evidence …1
• 50% of 353 critically ill children had initial
glucose >120 mg/dL ()
– Ruiz Magro P, et al [Metabolic changes in critically ill children]. An
Esp Pediatr 1999;51:143-8
Pediatric evidence …2 Hyperglycemia
Higher peak &
Pediatric evidence …3 5.7 times
for highest BS >
120 mg/dl in first
Portland Diabetic Project
Furnary et al. 2004, Endocr Pract
• 17-year prospective, NON randomized 4864
patients with diabetes + open-heart surgery
• Increasing BS levels directly associated with
– deep sternal wound infections (DSWI),
– length of hospital stay (LOS), and
– hospital cost.
• Continuous INSULIN, target BS < 150 mg/dL for
3- post op days, reduced …
– death by 57%
– DSWI by 66%,
– (P<0.0001 for both)
Krinsley JS: Mayo Clin Proc, 2004
• 800 patients from a medical surgical ICU
• Target BS < 140 mg/dl
• Mortality decreased 29%
• LOS in ICU decreased 11%
• Renal insufficiency diminished by 75%
• Transfusions patients decreased by 19%
• No increase in nurse staffing
• No significant increase in hypoglycemia
occurred (0.35 vs. 0.34%).
Detrimental effects of
• impairs immune function
–neutrophil function is reduced,
–complement binding is attenuated,
–monocyte phagocytic function is
disrupted PMN defect
• proinflammatory & prothrombotic
• cells membranes are altered
Pathophysiologic basis for benefits
• regulates vasomotor function and
contractility of the myocardium
• stimulates nitric oxide production,
• improves endothelial function
• lowers cytokines
• improves protein balance and fat
• complementary or synergistic
• overall improvements in immune,
hemodynamic, and metabolic functions
So What’s the catch?
How tight is too tight?
– Van den Berghe 0.05% vs 0.007%
– Krinsley: 0.35 vs. 0.34%
– abrupt interruption of Dextrose or continuous
• Risk-benefit ratio
• Insulin: Intravenous & continuous
• BS monitoring: hourly at least initially
• Essentially Nurse-led
• Adjustment protocol based not prn
• … and then, no two protocols are like
Complexity & variability of
• Nine protocols reviewed
• From 27 to 800 patients.
• Target: 80-110 mg/dL, to 126-207 mg/dL
• Titration: based only on current BS level, OR
current & previous BS, insulin sensitivity and
• Insulin adjustments: Units or % of previous dose
• BS checks: hourly, but varied in subsequent
• Mean time to achieve target 2 to 15 hours.
• Hypoglycemia threshold: from 40 to 70 mg/dl
What’s going on in the PICU?
• Before July 11, 2005
• After July 8, 2005
• A LOT!
• Approached to
develop a computer
• July 8:
• July 9, 10: Movie
• July 11th
PICU: Glucose Optimizer pilot ..
• First patient experience
– Over 60 days,
– over 1500 Protocol manipulations
– More than 15 nurses
– Minimal orientation of first few nurses
– Cruise control
– Even travelling nurses, relatively new nurses
– Demo program
– In actual use
• Paucity of published studies
– Hyperinsulinemic clamp
• 2004, the American Association of Clinical
Endocrinologists: inpatient & peri-operative
guidelines, ASA input
• 110 mg/dl as the upper limit during the
• American College of Endocrinology Position Statement on Inpatient
Diabetes and Metabolic Control. Endocrine Practice. 2004;
• Address hyperglycemia research on many
• National online survey
• Comparative study: Paper vs computerized
• Hospital wide implementation: Intranet
• Extremely rapid implementation cycle in
other hospitals, locally, nationally
• Palm pilot based program
• Integrating program with Glucometer
• Web-based nursing in-service &
• Will intra-op TGC improve outcomes
• Randomized study in PICU
This ICU has not yet implemented tight glucose control!
Until then, please pardon the inconvenience of our 40%
increased Mortality Rate!
We have come a long way !
Best & Banting, 1921
• A spoonful of sugar
makes the ….
– mortality go up
– infections go up
– ICU stay go up
– transfusions go up
– dialysis go up
– ventilators go up
– costs go up
•Hyperglycemia is v. common
•Hyperglycemia IS Bad
•Normoglycemia IS Good
•Tight Glycemic Control can
•We will take the challenge of
implementation at UMMS
•Lot’s going on in the PICU
•Future is exciting
• Finney, SJ, et al. Glucose control & mortality in
critically ill patients. JAMA 290:15, 2003.
• McGowen, KC, et al. Stress induced hyperglycemia.
Critical Care Clinics 17:1, 2001.
• Montori, VM, et al. Hyperglycemia in acutely ill
patients. JAMA 288:17, 2002.
• Van den Berghe, G. Insulin therapy for the critically
ill patient. Clinical Cornerstone 5:2, 2003.
• Van den Berghe, G, et al. Outcome benefit of
intensive insulin therapy in the critically ill: Insulin
dose vs. glycemic control. Critical Care Medicine 31:2,
Perioperative outcomes in
cardiac surgery patients
• Intraoperative hyperglycemia is an
independent risk factor for complications,
including death, after cardiac surgery
• Gandhi et al, Mayo Clin Proc. 2005
Hyperglycemia in ICU
• Metabolic changes in response to stress
∀↓ insulin secretion
∀↑ stress hormones (cortisol,
catecholamines, GH, glucagon)
∀↑ cytokines (TNFα , IL-1)
• Results in gluconeogenesis,
glycogenolysis, lipolysis, proteolysis