inpatient glycemic management patients with non-critical illness approaches and tools

Inpatient Glycemic Management Patients with Non-Critical illness Approaches and Tools

Inpatient Glycemic Management Definition of terms: Hospital hyperglycemia: Any BG > 140 mg/dl (7.8 mmol/L) Stress hyperglycemia: Elevations in blood glucose levels that occur in patients with no prior history of diabetes and A1c levels that are not significantly elevated ( 140 mg/dl (7.8 mmol/L) Stress hyperglycemia: Elevations in blood glucose levels that occur in patients with no prior history of diabetes and A1c levels that are not significantly elevated (

130 nonsurgical insulin-naive patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Randomly assigned to sliding scale insulin (SSI) or a basal-bolus regimen with glargine and glulisine 0.4 units per kg/day for BG 140-200 0.5 units per kg /day for BG > 200 50% given as glargine and 50% as glulisine Oral antidiabetic drugs discontinued 2 hypoglycemic events (BG < 60 mg/dl) in each group 130 nonsurgical insulin-naive patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Randomly assigned to sliding scale insulin (SSI) or a basal-bolus regimen with glargine and glulisine 0.4 units per kg/day for BG 140-200 0.5 units per kg /day for BG > 200 50% given as glargine and 50% as glulisine Oral antidiabetic drugs discontinued 2 hypoglycemic events (BG < 60 mg/dl) in each group Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial) Umpierrez et al. Diabetes Care. 30:2181 2007

Adjusting scheduled insulin regimen If fasting and premeal BG >140 mg/dl, dose of glargine increased by 20% For BG 140 mg/dl, dose of glargine increased by 20% For BG

Persistent hyperglycemia (BG>240 mg/dl) is common (15%) with SSI therapy Days of Therapy BG, mg/dL 100 120 140 160 180 200 220 240 Admit 1 Sliding-scaleBasal-bolus 260 280 300 3345672421 Rabbit 2 Trial: SSI Resulted in Uncontrolled Hyperglycemia in some Patients Hypoglycemia rate: Basal Bolus Group: BG < 60 mg/dL: 3% BG < 40 mg/dL: none SSRI: BG < 60 mg/dL: 3% BG < 40 mg/dL: none Basal Bolus Group: BG < 60 mg/dL: 3% BG < 40 mg/dL: none SSRI: BG < 60 mg/dL: 3% BG < 40 mg/dL: none Umpierrez GE, et al. Diabetes Care. 2007;30(9):2181-2186.

130 nonsurgical non-critically ill patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Half of patients were receiving insulin prior to admission and received similar outpatient insulin dose in the hospital Randomly assigned to: Detemir once a day with premeal Aspart 3 times a day NPH and regular twice a day before breakfast and dinner Dosing 0.4 units per kg/day for BG 140-200 0.5 units per kg /day for BG > 200 Distribution of insulin Determir group: 50% given as detemir and 50% as aspart NPH group: 2/3 given as NPH and 1/3 as regular 130 nonsurgical non-critically ill patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Half of patients were receiving insulin prior to admission and received similar outpatient insulin dose in the hospital Randomly assigned to: Detemir once a day with premeal Aspart 3 times a day NPH and regular twice a day before breakfast and dinner Dosing 0.4 units per kg/day for BG 140-200 0.5 units per kg /day for BG > 200 Distribution of insulin Determir group: 50% given as detemir and 50% as aspart NPH group: 2/3 given as NPH and 1/3 as regular Detemir with Aspart vs NPH with Regular Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes Umpierrez et al. J Clin Endocrinol Metab. 94:564 2009 DEAN Trial

Changes in Mean Daily Glucose BG, mg/dL Duration of Therapy, d Data are means SEM. Detemir + aspart NPH + regular Basal-bolus regimen: detemir was given once daily; aspart was given before meals. NPH/regular regimen: NPH and regular insulin were given twice daily, two thirds in AM, one third in PM. Basal-bolus regimen: detemir was given once daily; aspart was given before meals. NPH/regular regimen: NPH and regular insulin were given twice daily, two thirds in AM, one third in PM. Umpierrez GE, et al. J Clin Endocrinol Metab. 2009;94(2):564-569. P=NS 100 120 140 160 180 200 220 240 Pre-Rx BG 0123456-10 DEAN Trial

Copyright 2009 The Endocrine Society Umpierrez, G. E. et al. J Clin Endocrinol Metab 2009;94:564-569 Mean BG concentrations in hospitalized patients treated with detemir/aspart or NPH/regular Detemir/Aspart NPH/Regular DEAN Trial NPH/Regular BG < 40 mg/dl: 1.6% BG < 60 mg/dl: 25.4% NPH/Regular BG < 40 mg/dl: 1.6% BG < 60 mg/dl: 25.4% Detemir/Aspart BG < 40 mg/dl: 4.5% BG < 60 mg/dl: 32.8% Detemir/Aspart BG < 40 mg/dl: 4.5% BG < 60 mg/dl: 32.8% B L D HS

Umpierrez et al, J Clin Endocrinol Metab 94: 564569, 2009 DEAN Trial Treatment with basal/bolus regimen with detemir once daily and aspart before meals results in equivalent glycemic control and no differences in the frequency of hypoglycemia compared to a split-mixed regimen of NPH and regular insulin in patients with type 2 diabetes. Commentary NPH insulin was administered twice a day in this study Detemir insulin was administered once a day It is possible that detemir insulin may need to be administered twice a day Commentary NPH insulin was administered twice a day in this study Detemir insulin was administered once a day It is possible that detemir insulin may need to be administered twice a day

*p-values are from Wilcoxon Two-Sample Test Risk Factors for Hypoglycemia Umpierrez et al, ADA Scientific Meeting, Poster #516 p-value * VariableBG < 60 mg/dlBG < 70 mg/dl Age0.0360.001 Weight0.0270.001 A1C0.5210.658 Creatinine0.0110.002 Enrollment BG0.1660.319 Previous treatment 0.005

Treatment Algorithm For Patients Receiving Continuous Enteral Nutrition 2 BG > 130 mg/dl Continue current regimen 2 BG >180 mg/dl in prior 24 hours Add 25-50% Correction Insulin to Glargine Administer regular insulin q6h 2 BG >180 mg/dl in prior 24 hours Add 25-50% Correction Insulin to Glargine Administer regular insulin q6h Glargine 10 units + Correction Insulin q6h Patient with no prior history diabetes started on EN All BG < 130 mg/dl Discontinue BG Monitoring BG < 130 mg/dl x 48 hrs

Alternative Treatment Algorithm For Patients Receiving Continuous Enteral Nutrition 2 BG > 130 mg/dl Continue regimen 2 BG >180 mg/dl in prior 24 hours 1 BG > 250 mg/dl in prior 24 hours 2 BG >180 mg/dl in prior 24 hours 1 BG > 250 mg/dl in prior 24 hours Initiate correction insulin q6h All BG < 180 mg/dl Discontinue BG Monitoring BG < 130 mg/dl x 48 hrs Patient with no prior history diabetes started on EN Start Scheduled Insulin Therapy

GlargineCI*P value Mean CBG during study mg/dl1633116130.75 Hypoglycemia/pt days %2.74.8.34 Hyperglycemia/pt days %49.347.6.77 Blood Glucose Data on Participants According to Group Korytkowski M, Salata R, Koerbel G et al Diabetes Care 32:594, 2009 There were no group differences in adverse events. *CI= correction insulin

Summary 50% of eligible subjects for this study had no previous history of type 2 diabetes or hyperglycemia Both glargine and correction insulin (CI) (with the addition of NPH) were effective at achieving glycemic control in these patients with careful glucose monitoring and adjustments of the insulin regimen 13/25 patients randomized to correction insulin alone required NPH insulin to achieve glycemic control No severe hypoglycemia events occurred during this study 50% of eligible subjects for this study had no previous history of type 2 diabetes or hyperglycemia Both glargine and correction insulin (CI) (with the addition of NPH) were effective at achieving glycemic control in these patients with careful glucose monitoring and adjustments of the insulin regimen 13/25 patients randomized to correction insulin alone required NPH insulin to achieve glycemic control No severe hypoglycemia events occurred during this study Korytkowski M, Salata R, Koerbel G et al Diabetes Care 32:594, 2009

Implications of this study Bedside glucose monitoring is recommended for all hospitalized patients with and without a prior history of diabetes with initiation or augmentation of enteral nutrition. Glargine insulin is effective at achieving and maintaining glycemic control in patients receiving both continuous and intermittent enteral nutrition without increasing the risk for hypoglycemia. Bedside glucose monitoring is recommended for all hospitalized patients with and without a prior history of diabetes with initiation or augmentation of enteral nutrition. Glargine insulin is effective at achieving and maintaining glycemic control in patients receiving both continuous and intermittent enteral nutrition without increasing the risk for hypoglycemia. Korytkowski M, Salata R, Koerbel G et al Diabetes Care 32:594, 2009

Glycemic Management of the Patient Receiving Enteral Nutrition Continuous enteral nutrition (EN) Basal: 40-50% of TDD as long or intermediate acting insulin given once twice a day Short acting 50-60% of TDD given q6h Cycled enteral nutrition Intermediate acting insulin given together with a rapid or short acting insulin with start of TF Rapid or short acting insulin administered q4 to 6 hours for duration of EN administration Correctional insulin given for BG above goal range Bolus enteral nutrition Rapid acting analog or short acting insulin given prior to each bolus Continuous enteral nutrition (EN) Basal: 40-50% of TDD as long or intermediate acting insulin given once twice a day Short acting 50-60% of TDD given q6h Cycled enteral nutrition Intermediate acting insulin given together with a rapid or short acting insulin with start of TF Rapid or short acting insulin administered q4 to 6 hours for duration of EN administration Correctional insulin given for BG above goal range Bolus enteral nutrition Rapid acting analog or short acting insulin given prior to each bolus

Glycemic Management of the Patient Receiving Enteral Nutrition Suggested Dose of short acting insulin can be based on anticipated dose of carbohydrate Example: 67 yo woman receiving Peptamin with calculated 188 G of carbohydrate over 24 hrs Insulin to carbohydrate ratio: 1 unit/10 G Calculated total insulin dose 19 units Administered total insulin dose over 24 h 20 units BG over 1 st 36 hours 90-135 mg/dl Suggested Dose of short acting insulin can be based on anticipated dose of carbohydrate Example: 67 yo woman receiving Peptamin with calculated 188 G of carbohydrate over 24 hrs Insulin to carbohydrate ratio: 1 unit/10 G Calculated total insulin dose 19 units Administered total insulin dose over 24 h 20 units BG over 1 st 36 hours 90-135 mg/dl

Recommendations for Patients Receiving Parenteral and Enteral Nutrition Initiate bedside capillary blood glucose (CBG) monitoring for all patients receiving enteral nutrition (EN). Continue glucose monitoring during upward (or downward) titrations of enteral nutrition Initiate correctional insulin for any patient with CBG levels > 140 mg/dL during EN. Consider use diabetes-specific formulas in patients with pre-existing diabetes. Consider use of Diabetes-specific formulas in patients with new onset or difficult to control hyperglycemia. Initiate bedside capillary blood glucose (CBG) monitoring for all patients receiving enteral nutrition (EN). Continue glucose monitoring during upward (or downward) titrations of enteral nutrition Initiate correctional insulin for any patient with CBG levels > 140 mg/dL during EN. Consider use diabetes-specific formulas in patients with pre-existing diabetes. Consider use of Diabetes-specific formulas in patients with new onset or difficult to control hyperglycemia.

Glycemic Management of the Patient Receiving Enteral Nutrition Patients who already have an underlying diagnosis of diabetes are likely to experience further elevations in blood glucose levels with the initiation of enteral nutrition 1. Patients receiving EN often have a higher severity of illness that those who do not. Unanticipated dislodgement of a feeding tube, temporary discontinuation of the feedings, or changes in the rate of administration can result in hypoglycemia. Protocols for avoidance and early treatment of hypoglycemia are recommended in case of abrupt discontinuation of EN. For example: Keep order in place to start dextrose-containing IVFs in event of abrupt discontinuation of EN Patients who already have an underlying diagnosis of diabetes are likely to experience further elevations in blood glucose levels with the initiation of enteral nutrition 1. Patients receiving EN often have a higher severity of illness that those who do not. Unanticipated dislodgement of a feeding tube, temporary discontinuation of the feedings, or changes in the rate of administration can result in hypoglycemia. Protocols for avoidance and early treatment of hypoglycemia are recommended in case of abrupt discontinuation of EN. For example: Keep order in place to start dextrose-containing IVFs in event of abrupt discontinuation of EN

Enteral Nutritional Support and Use of Diabetes Specific Formulas Standard formulas High in carbohydrate Low Fat Low fiber Standard formulas High in carbohydrate Low Fat Low fiber Diabetes Specific Formulas 3540% of calories from carbohydrate 15% of calories from fructose 40-50% of calories from fat with a large contribution from MUFAs (e.g. >60% of fat calories) Diabetes Specific Formulas 3540% of calories from carbohydrate 15% of calories from fructose 40-50% of calories from fat with a large contribution from MUFAs (e.g. >60% of fat calories) Marinos et al. Diabetes Care 28:2267 2005

Postprandial Rise in Blood Glucose and Type of EN Formula Marinos et al Diabetes Care 28:2267 2005 N = 20 Hi MUFA fructose fibre Peters 1989 N = 40 Hi MUFA fructose fibre Stanz Paris 1998 N = 12 Hi MUFA fructose fibre Stanz Paris 1998 N = 61 Hi MUFA fructose fibre Mesejo 2003 Meta analysis Long term N = 34 Hi MUFA fructose fibre Craig 1998 N = 11 Hi MUFA fructose fibre del Carmen Crespillo 2003 Meta analysis Short term Meta analysis All studies Favors specific Favors Standard -6 -4 -2 0 2 4 6 Postprandial rise in BG reduced by 18 mg/dl (1.03 mmol)

Peak Blood Glucose and Type of EN Formula Marinos et al Diabetes Care 28:2267 2005 N = 24 Hi MUFA fructose fibre Hofman 2004 Meta analysis Favors specific Favors Standard -3 -2 -1 0 1 2 3 N = 20 Hi MUFA fructose fibre Hofman 2004 Postprandial rise in BG reduced by 29 mg/dl (1.59 mmol)

Glycemic Management of the Patient Receiving TPN Usual method Adding incremental doses of insulin to TPN based on previous days requirement of correctional (sliding scale insulin) Other (preferred?) Use of a separate IV insulin infusion titrated according to bedside glucose levels There are no controlled trials examining different strategies for achieving glycemic control in this group of patients Usual method Adding incremental doses of insulin to TPN based on previous days requirement of correctional (sliding scale insulin) Other (preferred?) Use of a separate IV insulin infusion titrated according to bedside glucose levels There are no controlled trials examining different strategies for achieving glycemic control in this group of patients

Glycemic Management of the Patient Receiving TPN Suggested In patients with known type 2 diabetes, add 1 unit for each 10 Grams of carbohydrate in the solution Initiate Correctional Insulin Scale for BG > 140 mg/dl Add 60 to 100% of previous days correctional insulin dose to next days TPN solution Consider Add basal long or intermediate acting insulin at a dose of 0.2 to 0.4 units per kg per day Suggested In patients with known type 2 diabetes, add 1 unit for each 10 Grams of carbohydrate in the solution Initiate Correctional Insulin Scale for BG > 140 mg/dl Add 60 to 100% of previous days correctional insulin dose to next days TPN solution Consider Add basal long or intermediate acting insulin at a dose of 0.2 to 0.4 units per kg per day

Frequency of hyperglycemia in patients receiving high dose steroids % % Donihi A et al Endocrine Practice 12:358, 296 > 1 BG > 200 mg/dl> 2 BG > 200 mg/dl 64 56 81 52 41 75 0 0 30 60 90 All No Hx DM Hx DM

Steroid Therapy and Inpatient Glycemic Control The majority of patients receiving > 2 days of glucocorticoid therapy at a dose equivalent of at least 40 mg per day of Prednisone developed hyperglycemia No glucose monitoring was performed in 24% of patients receiving high dose glucocorticoid therapy The majority of patients receiving > 2 days of glucocorticoid therapy at a dose equivalent of at least 40 mg per day of Prednisone developed hyperglycemia No glucose monitoring was performed in 24% of patients receiving high dose glucocorticoid therapy Donihi A et al Endocrine Practice 12:358, 296

Risk for New Onset Diabetes with Glucocorticoid Therapy Clore JN, Thurber-Hay L. Endocrine Practice 15:469 2009

One Suggested Approach for Treatment of Hyperglycemia in Patients Receiving Glucocorticoid Therapy Clore JN, Thurber-Hay L. Endocrine Practice 15:469 2009 Prednisone (mg/day)NPH (units/kg/day)* > 400.4 300.3 200.2 100.1 *Administered in AM at time of prednisone administration Glargine preferred if dexamethasone used or Prednisone given twice a day *Administered in AM at time of prednisone administration Glargine preferred if dexamethasone used or Prednisone given twice a day

How do Steroids Differ in their Effects? Steroid Potency and Duration of Action 20mg/d of prednisone ~= 80mg/d of hydrocortisone ~= 16mg/d of methylprednisolone ~= 3mg/d dexamethasone) Glucocorticoid PotencyBiologic Half Life Hydrocortisone18-12 hours Prednisone418-36 hours Methylprednisolone518-36 hours Dexamethasone30-4036-54 hours

Steroid Therapy and Glycemic Control General Guidelines The majority of patients (but not all) receiving high dose glucocorticoid therapy will experience elevations in blood glucose For patients without prior DM or hyperglycemia or those with diabetes controlled with oral agents: Initiate glucose monitoring with low dose correction insulin scale administered prior to meals For patients previously treated with insulin Increase total daily dose by 20 to 40% with start of high dose steroid therapy Increase correctional insulin by one step (low to moderate dose) Adjust insulin as needed to maintain glycemic control The majority of patients (but not all) receiving high dose glucocorticoid therapy will experience elevations in blood glucose For patients without prior DM or hyperglycemia or those with diabetes controlled with oral agents: Initiate glucose monitoring with low dose correction insulin scale administered prior to meals For patients previously treated with insulin Increase total daily dose by 20 to 40% with start of high dose steroid therapy Increase correctional insulin by one step (low to moderate dose) Adjust insulin as needed to maintain glycemic control

IV Insulin Infusions may be required to maintain glycemic control in some patients Steroid Therapy and Glycemic Control General Guidelines

Glucocorticoid Therapy Suggested approach : Institute glucose monitoring for at least 48 hours in all patients Prescribe insulin therapy as needed according to results of bedside BG monitoring During initiation and taper of steroid therapy, proactive adjustment of insulin therapy can help avoid uncontrolled hyperglycemia and hypoglycemia. Suggested approach : Institute glucose monitoring for at least 48 hours in all patients Prescribe insulin therapy as needed according to results of bedside BG monitoring During initiation and taper of steroid therapy, proactive adjustment of insulin therapy can help avoid uncontrolled hyperglycemia and hypoglycemia.

Bromage et al. Surg Gynecol Obstet June 1971 Changes in Blood Glucose During Surgery in Patients without Diabetes General Anesthesia Epidural Anesthesia % Change in blood glucose 70%

Pre-Op Recommendations for Patients Admitted Day of Surgery Oral Hypoglycemic Agents Withhold oral agents the morning of surgery Insulin is necessary to control blood glucose in patients with BG > 150 during surgery Oral agents can be resumed postoperatively when Patient is reliably taking PO Risk of liver, kidney and heart failure are minimized Withhold oral agents the morning of surgery Insulin is necessary to control blood glucose in patients with BG > 150 during surgery Oral agents can be resumed postoperatively when Patient is reliably taking PO Risk of liver, kidney and heart failure are minimized

Give at least 50 to 70 % of usual dose of NPH insulin and 70 to 100 % of detemir or glargine insulin For patients receiving premix insulin (70/30 or 75/25), give 1/3 of total dose as NPH insulin prior to the procedure For patients undergoing prolonged procedures (e.g. CABG) hold SQ insulin and start IV insulin infusion Give at least 50 to 70 % of usual dose of NPH insulin and 70 to 100 % of detemir or glargine insulin For patients receiving premix insulin (70/30 or 75/25), give 1/3 of total dose as NPH insulin prior to the procedure For patients undergoing prolonged procedures (e.g. CABG) hold SQ insulin and start IV insulin infusion Pre-op Recommendations for Patients Admitted Day of Surgery Insulin Treated Patients

Mucha et al. Diabetes Care 27:1209 2004 Study of Glargine Insulin During Fasting in Subjects with Type 1 Diabetes Plasma glucose mg/dl Fasting Control Usual dose of glargine insulin administered while fasting or on another day in combination with usual prandial insulin (Control) N = 15 This study suggests the safety of administering a percentage of basal insulin when a patient is made NPO.

DC insulin pump and change to IV insulin according to patients current basal rate If basal rate < 1 unit/h, start IV insulin at 0.5 units/h h If basal rate 1-2 units/h, start IV insulin at 1 units/h Preoperative Recommendations Patients using insulin pump therapy Hypoglycemia and hyperglycemia are treated in manner similar to that of patients receiving SQ insulin pre-op

General Guidelines Inpatient use of U500 insulin is reserved for patients who use this concentrated form of regular insulin as outpatients and who demonstrate a similar or greater degree of insulin resistance at time of hospital admission. To avoid dosing errors that have potential for hypoglycemia, many hospitals regulate the administration of U500 insulin by requiring one or all of the following: Order written as volume to be given using a TB syringe All doses prepared in pharmacy Alerts in patient room and on patient medicine administration record General Guidelines Inpatient use of U500 insulin is reserved for patients who use this concentrated form of regular insulin as outpatients and who demonstrate a similar or greater degree of insulin resistance at time of hospital admission. To avoid dosing errors that have potential for hypoglycemia, many hospitals regulate the administration of U500 insulin by requiring one or all of the following: Order written as volume to be given using a TB syringe All doses prepared in pharmacy Alerts in patient room and on patient medicine administration record Can U500 Regular Insulin Be Used in the Hospital?

Management of Hyperglycemia in the Hospital and Patient Safety Concern Both under and over-treatment of hyperglycemia create safety concerns in hospitalized patients. Areas of risk: Changes in carbohydrate or food intake Changes in clinical status or medications Failure to adjust therapy based on BG patterns Prolonged use of SSI as monotherapy Poor coordination of BG testing with insulin administration and meal delivery Poor communication during patient transfers Errors in order writing and transcription Both under and over-treatment of hyperglycemia create safety concerns in hospitalized patients. Areas of risk: Changes in carbohydrate or food intake Changes in clinical status or medications Failure to adjust therapy based on BG patterns Prolonged use of SSI as monotherapy Poor coordination of BG testing with insulin administration and meal delivery Poor communication during patient transfers Errors in order writing and transcription

Summary BG levels of 100-180 mg/dl are suggested for the majority of non-critically ill patients Insulin therapy the preferred method for achieving and maintaining glycemic control in the hospital Scheduled SQ Basal Bolus insulin therapy is effective and safe for treatment of hyperglycemia in non-critically ill patients Correction insulin alone may be appropriate for periods of < 24 to 48 hours in patients without a prior history of diabetes or prior insulin therapy with initiation of therapies known to be associated with high risk for hyperglycemia (TPN, EN, Steroids) Prolonged monotherapy with correction insulin is inappropriate once an insulin requirement is established with correction insulin Proactive adjustments in the hypoglycemic regimen are required for both initiation and tapering of steroid therapy BG levels of 100-180 mg/dl are suggested for the majority of non-critically ill patients Insulin therapy the preferred method for achieving and maintaining glycemic control in the hospital Scheduled SQ Basal Bolus insulin therapy is effective and safe for treatment of hyperglycemia in non-critically ill patients Correction insulin alone may be appropriate for periods of < 24 to 48 hours in patients without a prior history of diabetes or prior insulin therapy with initiation of therapies known to be associated with high risk for hyperglycemia (TPN, EN, Steroids) Prolonged monotherapy with correction insulin is inappropriate once an insulin requirement is established with correction insulin Proactive adjustments in the hypoglycemic regimen are required for both initiation and tapering of steroid therapy

inpatient glycemic management patients with non-critical illness approaches and tools

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