What s so sweet about glycemic control? June 3, 2016

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1 What s so sweet about glycemic control? June 3, 2016

4 Objectives Provide an overview of why glucose control is important in surgical patient outcomes. Demonstrate an understanding of how anesthetics and surgery can impact the body s ability to remain within glycemic boundaries Outline the optimal surgical patient glycemic goal range. Identify the effectiveness of glycemic control on mortality and morbidity of adult patients during the intra and post-operative period. Discuss possible change ideas to implement glucose control.

5 2016 CANADIAN SURGICAL SITE INFECTION PREVENTION AUDIT Dr. Claude Laflamme March 24, 2016

6 Audit Participation Sites 52 Patients 2082 Clean I & II 1998

7 Participants by Type of Surgery

8 I. Hair Removal Method n = 1816 Sites 52 Patients % 4% Not Recorded = 15

9 E. Prophylactic Abx administration n = 1957 Sites 52 Patients % 9%

10 K. Temperature at end of surgery or on arrival in PACU degrees C n = 1563 Sites 52 Patients % 15% Not Recorded = 100

11 J. Glucose was below 11.1 mmol/l on each of POD 0, 1 and 2 n = 390 Sites 34 Patients % 43% Not Recorded = 7 Note: Not at Risk (not diabetic) excluded from this measure (n=1513)

12 J. Glucose was below 11.1 mmol/l on each of POD 0, 1 and 2 Total Patients 355 n = 111 n = 141 n = 31 n = 10 66% 56% 32% 60% Note: Not at Risk (not diabetic) excluded from this measure

1 mmol/l Evidence Time Never SHEA: Less than 10 mmol/l CDC

13 Peri-Operative Glucose Control Goal Pre, Intra and Post Blood Glucose below mmol/l Evidence Time Never SHEA: Less than 10 mmol/l CDC (draft): Less than 11.1 mmol/l hrs pre-op Intra-op hrs post-op Aim for 4-6 mmol/l

14 The BC Perspective Curt Smecher Anesthesiologist Abbotsford Regional Hospital

15 Surgical Site Infections and Diabetes Marshall Dahl MD PhD FRCPC cert Endo Clinical Professor, Endocrinology, University of British Columbia Jordanna Kapeluto MD FRCPC Endocrinology Fellow, University of British Columbia

16 People with Diabetes are More Susceptible to Infections Mucormycosis Malignant otitis externa Emphysematous cholecytisis Necrotizing fascitis Pyomyositis Urinary tract infections Surgical site infections Foot infections Superficial fungal infections 1

17 People with Diabetes are More Susceptible to Infections Mucormycosis Malignant otitis externa Emphysematous cholecytisis Necrotizing fascitis Pyomyositis Urinary tract infections Surgical site infections Foot infections Superficial fungal infections 1

18 Hyperglycemia Impairs Immune Response Neutrophil function is impaired during hyperglycemia Chemotaxis, phagocytosis Cell-mediated immunity and Complement system are also impaired Occurs in laboratory setting by increasing glucose concentration in normal blood (glucose >11.1) Occurs in diabetes serum vs non-diabetes serum 2

19 CDC definition: Surgical Site Infection (SSI) infection related to an operative procedure occurs at or near the surgical incision within 30 days of the procedure within one year if prosthetic material is implanted at surgery SSIs are often localized to the incision site but can also extend into deeper adjacent structures Horan TC et al: Infect Control Hosp Epidemiol. 1992;13(10):606 3

20 Perioperative Hyperglycemia and SSI Risk N = 2090 general and vascular surgery patients Retrospective review Multivariate analysis: age, emergency status, ASA classes P3-P5, operative time, diabetes, plus postoperative glucose level. Colorectal patients: only postoperative glucose control a significant predictor of SSI (OR 3.2) Vascular surgery patients: operative time and diabetes were independent predictors of SSI Postoperative hyperglycemia may be the most important risk factor for SSI. Aggressive early postoperative glycemic control should reduce the incidence of SSI. Ata el al; Arch Surg 2010; 145 (9): 858 4

21 What glucose levels correlate with infection risk? Ata el al; Arch Surg 2010; 145 (9): 858 5

22 One Million US Joint Arthroplasty Patients Controlled diabetes: more UTIs vs non-diabetes Uncontrolled diabetes: more UTIs and overall infections vs controlled diabetes J Bone Joint Surg Am. 2009;91(7):1621 6

23 Is it pre-existing diabetes control or perioperative control? Prospective, 1000 patients, cardiothoracic surgery Predictors of SSI: independent risk factors Diabetes (OR 2.76) Postoperative hyperglycemia [>11.1] (OR 2.02) Among patients with known diabetes, elevated A1c not associated with risk of SSI Perioperative management and acute control of glucose more important than diabetes status before surgery Infect Control Hosp Epidemiol. 2001;22(10):607 7

24 When do SSIs occur? NSQIP, 50,000 patients, vascular surgery Diabetes significantly associated with SSI post discharge J Vasc Surg. 2015;62(4):

25 Effects of target glucose on postoperative infections Systematic review Cardiac surgery intervention trials four randomized six cohort studies Continuous insulin infusion vs sub-cutaneous sliding-scale target < 11 mmol/l Note that control is not tight Significant reduction in SSIs compared with standard management. Heart Lung. 2015;44(5):430 9

26 Other Factors in Diabetes that Predispose to SSIs Vascular Insufficiency Tissue ischemia, anaerobic bacteria Sensory peripheral neuropathy Local trauma and ulceration Autonomic neuropathy Urinary retention and stasis Increased skin and nasal colonization More frequent S. Aureus and methicillin-resistance Increased E. Coli binding to bladder epithelium 10

with AMI; OGTT at discharge 31%; 3 months 25% 62% Normoglycemia Umpierrez G et al.

27 Hyperglycemia in Hospital Common: ICD Codes 13% DM reason for hospitalization in 8% 12% New Hyperglycemia Laboratory values 13% 26% Known Diabetes Patients admitted with AMI; OGTT at discharge 31%; 3 months 25% 62% Normoglycemia Umpierrez G et al. J Clin Endocrinol Metab 2002;87: Clement S et al. Diab Care 2004; 27(2):

Hyperglycemia in Hospital Type 2 Diabetes Hospitalization Hyperglycemia Coronary artery disease Cerebrovascular disease Peripheral vascular disease Nephropathy Infection Amputations 62% 12% 26%

28 Hyperglycemia in Hospital Type 2 Diabetes Hospitalization Hyperglycemia Coronary artery disease Cerebrovascular disease Peripheral vascular disease Nephropathy Infection Amputations 62% 12% 26% Surgery Infection Glucocorticoids Vasopressors Calcineurin inhibitors Total parenteral nutrition (TPN) Continuous enteral feeds New Hyperglycemia Known Diabetes Normoglycemia Umpierrez G et al. J Clin Endocrinol Metab 2002;87: Clement S et al. Diab Care 2004; 27(2):

Hyperglycemia in Hospital Type 2 Diabetes Hospitalization Hyperglycemia Barriers to glycemic control Fear of hypoglycemia Holding usual diabetes treatment Reliance on reactive insulin regimens

29 Hyperglycemia in Hospital Type 2 Diabetes Hospitalization Hyperglycemia Barriers to glycemic control Fear of hypoglycemia Holding usual diabetes treatment Reliance on reactive insulin regimens (sliding scale) Caregiver comfort with management PO intake/ Meal timing Meal interruption Timing of medication administration Dextrose in IVF AKI Activity/Mobility Umpierrez G, et al. J Hosp Med 2006;1: Clement S et al. Diab Care 2004; 27(2): Umpierrez G, et al. Am J Med 2007;120:

30 Hyperglycemia in Acute Illness Increased stress hormone levels Increased epinephrine Increased cortisol Decreased level of activity Glucocorticoid therapy Continuous enteral nutrition Parenteral nutrition Acute illness Hyperglycemia Decreased immune function Decreased wound healing Increased oxidative stress Endothelial dysfunction Increase in inflammatory factors Procoagulant state Increased mitogen levels Fluid shifts Electrolyte fluxes Potential exacerbation of myocardial and cerebral ischemia Inzucchi SE. N Engl J Med 2006;355: Clement S et al. Diab Care 2004; 27(2):

31 Hyperglycemia-Related Morbidity and Mortality Study Patient Population Glycemic Cutoff Hyperglycemia Related Outcomes Pomposelli et al Umpierrez et al DM undergoing general surgery procedure All surgical and medical patients (87% non-icu) BG >12.2 on POD1 FBG >7.0 RBG >11.1 Capes et al Acute MI BG >6.1 no DM BG >6.9 with DM Nosocomial infection (Sn 85%) 2.7x RR in-hospital mortality More ICU admission Longer LOS 3.9x RR in-hospital mortality in non-dm 1.7x RR in-hospital mortality in DM Risk CHF and cardiogenic shock Pomposelli J et al. J Parenter Enter Nutr, 1998; 22:77-81 Umpierrez G et al. J Clin Endocrinol Metab 2002;87: Capes S et al. Lancet, 2000; 355:

32 Hyperglycemia-Related Morbidity and Mortality Study Patient Population Glycemic Cutoff Hyperglycemia Related Outcomes Baker et al AECOPD < >9.0 Longer LOS 15% increase AE for each 1.0mmol/L increase BG Increased mortality risk Cheung et al TPN 7.0 Incr. 1.0 mmol/l incr. complications by factor 1.58 McAlister et al CAP 7.0 Longer LOS Incr. in-hospital complications Incr. mortality risk Baker EH, et al. Thorax 2006;61:284-9 Cheung NW, et al. Diab Care 2005;28: ; McAlister FA, et al. Diabe Care 2005;28:

33 Blood Glucose Targets: AACE/ADA Consensus Non-critically Ill Patients Pre-meal Blood Glucose BG) Random Blood Glucose (BG) Medical Illness <7.8 mmol/l <10.0 mmol/l Surgical Illness <7.8 mmol/l <10.0 mmol/l Critically Ill Patients (CDA) Peri-operative CV Surgery intraop Critical Care Unit mmol/l mmol/l mmol/l Malmberg K et al. J Am Coll Cardiol 1995;26(1):57-65 Clement S et al. Diab Care 2004; 27(2): Moghissi ES, et al. Endocr Pract 2009;15:

Sliding Scale Insulin BG (mmol/l) Bolus insulin (U) <4 Hypoglycemia Protocol and Call MD 4.1 6.0 0 6.1-8 0 8.1-10.0 2 10.

34 Sliding Scale Insulin BG (mmol/l) Bolus insulin (U) <4 Hypoglycemia Protocol and Call MD Under correct T2DM Reactive Does not account for prandial intake Assumes all hyperglycemia is uniform Stacking > and Call MD Over correct T1DM 18

35 Sliding Scale Insulin (SSI) BG (mmol/l) 16.5 What do you do? BG (mmol/l) Bolus insulin (U) U What do you do? +10 U <4 Hypoglycemia Protocol and Call MD What do you do? What do you do? 0 U 0 U Breakfast Lunch Dinner Bedtime Bolus insulin QID > and Call MD Adapted From Sliding Scale to Basal-Bolus 19

36 Sliding Scale Insulin (SSI) Higher Mean Glucose Levels and Poorer Outcomes Mean BG (mmol/l) Retrospective Chart review 391 patients, age > 45, pneumonia Cardiovascular complications or death Sepsis or ICU admission Odds Ratio 95% CI No Sliding Scale (Scheduled insulin) Sliding-scale insulin BG: blood glucose; CI: confidence interval; ICU: intensive care unit Adapted from: Becker T, et al. Diabetes Res Clin Pract 2007;78: Slide courtesy of Dr. Paty 20

37 Basal Bolus Insulin (BBI) Scheduled Insulin Insulin given consistently + Supplemental Insulin Insulin given prn if above target Basal Long acting 1-2x per day Baseline secretion Steady/Euglycemia Bolus Prandial Nutritional Rapid or Short acting 2+ per day Prandial surge Correction Rapid or Short acting ac meals Modified sliding scale 21

38 Basal Bolus Insulin (BBI) RABBIT 2/Surgery Basal bolus insulin vs. sliding scale insulin RABBIT 2 (2007) RABBIT 2 Surgery (2011) Patient Population Regimen Outcomes T2DM; Medical inpatients T2DM; Surgical Inpatients Glargine Glulisine Glargine Glulisine Better with BBI vs. SSI Better with BBI vs. SSI More hypoglycemia No difference severe hypoglycemia Less hospital complications Complications (trend): Nosocomial pneumonia Wound infection Renal failure Bacteremia Admission to ICU Death 1 in each group Umpierrez GE, et al. Diabetes Care 2007;30: Umpierrez GE, et al. Diabetes Care 2011;34:

39 CDA Recommendations Recommendation 1 1. Provided that their medical conditions, dietary intake, and glycemic control are acceptable, people with diabetes should be maintained on their pre-hospitalization oral anti-hyperglycemic agents or insulin regimens [Grade D, Consensus] 23

40 CDA Recommendations Recommendation 2 2. For hospitalized patients with diabetes treated with insulin, a proactive approach that includes basal, bolus, and correction (supplemental) insulin, along with pattern management, should be used to reduce adverse events and improve glycemic control, instead of the reactive slidingscale insulin approach that uses only short- or rapid-acting insulin [Grade B, Level 2] 24

41 CDA Recommendations Recommendation 3 and 4 3. For the majority of non critically ill patients treated with insulin, pre-meal BG targets should be 5.0 to 8.0 mmol/l in conjunction with random BG values <10.0 mmol/l, as long as these targets can be safely achieved [Grade D, consensus] 4. For most medical/surgical critically ill patients with hyperglycemia, a continuous IV insulin infusion should be used to maintain glucose levels between mmol/l [Grade D, consensus] 25

42 CDA Recommendations Recommendation 5 and 6 5. To maintain intraoperative glycemic levels between mmol/l for patients with diabetes undergoing CABG, a continuous IV insulin infusion protocol administered by trained staff, [Grade C, Level 3] should be used 6. Perioperative glycemic levels should be maintained between mmol/l for most other surgical situations, with appropriate protocol and trained staff to ensure safe and effective implementation of therapy and to minimize the likelihood of hypoglycemia [Grade D, Consensus] 26

43 CDA Recommendations Recommendation 7 7. In hospitalized patients, hypoglycemia should be avoided: Protocols for hypoglycemia avoidance, recognition and management should be implemented with nurse initiated treatment, including glucagon for severe hypoglycemia when IV access is not readily available [Grade D, consensus] Patients at risk of hypoglycemia should have ready access to an appropriate source of glucose (oral or IV) at all times, particularly when NPO or during diagnostic procedures [Grade D, Consensus] 27

44 CDA Recommendations Recommendation 8 and 9 8. Healthcare professional education, insulin protocols and order sets may be used to improve adherence to optimal insulin use and glycemic control [Grade C, Level 3] 9. Measures to assess, monitor, and improve glycemic control within the inpatient setting should be implemented, as well as diabetesspecific discharge planning [Grade D, Consensus] 28

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Inpatient Management of Diabetes Mellitus. Jessica Garza, Pharm.D. PGY-1 Pharmacotherapy Resident TTUHSC School of Pharmacy

Inpatient Management of Diabetes Mellitus Jessica Garza, Pharm.D. PGY-1 Pharmacotherapy Resident TTUHSC School of Pharmacy 2 Disclosure Jessica Garza does not have any actual or potential conflicts of