Building and Implementing Effective Subcutaneous Insulin Orders and Protocols

1. Building and Implementing Effective Subcutaneous Insulin Orders and Protocols Greg Maynard MD, MS Professor of Clinical Medicine and Chief, Division of Hospital Medicine University of California, San Diego

2. Insulin Terminology Basal insulin Long-acting, all Type 1 and most Type 2 DM patients should have basal insulin whether they are eating or not (insulin glargine, insulin detemir, or NPH) Nutritional or pre-meal / prandial insulin Short-acting insulin given with meals in anticipation of carbohydrate load glycemic spike (scheduled insulin aspart, insulin lispro, insulin glulisine, regular insulin) Correction or supplemental insulin Short-acting insulin given to cover high glucose; if substantial use, it should drive adjustment of basal and nutritional insulins

3. Insulin Terminology Sliding scale insulin This is a dirty word; we don�t use dirty words at UCSD �Mindless medicine,� �paralysis of thought,� �action without benefit,� �insulin insanity� Evidence does not support this technique without basal insulin; unacceptably high rates of Hyperglycemia Hypoglycemia and insulin stacking Iatrogenic DKA in patients with type 1 DM

4. Steps for Successful Implementation Identify best practices and preferred regimens Integrate into a protocol, summarize in one page. Place protocol guidance into flow of work Structured order sets, documentation tools, prompts Use high reliability design, layer on other improvement methods (including special teams) Proactively identify and mitigate outliers. Refine and redesign your educational efforts, order set design, and implementation strategies accordingly. Identify best practices and preferred regimens to manage the hyperglycemic inpatient each common category of nutritional intake and special situations. Integrate best practices and preferred institutional choices into an inpatient glycemic control protocol. Crystallize your protocol into a one page summary. Place guidance from your protocol into the flow of work, by integrating it into standardized subcutaneous insulin order sets and other documentation and treatment tools. Use high reliability design and other performance improvement methods to enhance a successful implementation and standardization of the process. Proactively identify inpatients that continue to have uncontrolled hyperglycemia, in spite of your protocol and order set interventions. Refine and redesign your educational efforts, order set design, and implementation strategies accordingly. Identify best practices and preferred regimens to manage the hyperglycemic inpatient each common category of nutritional intake and special situations. Integrate best practices and preferred institutional choices into an inpatient glycemic control protocol. Crystallize your protocol into a one page summary. Place guidance from your protocol into the flow of work, by integrating it into standardized subcutaneous insulin order sets and other documentation and treatment tools. Use high reliability design and other performance improvement methods to enhance a successful implementation and standardization of the process. Proactively identify inpatients that continue to have uncontrolled hyperglycemia, in spite of your protocol and order set interventions. Refine and redesign your educational efforts, order set design, and implementation strategies accordingly.

5. Integrate Best Practice into protocols, order sets, documentation Actionable glycemic target Constant carbohydrate / dietary / consult A1c Specify hyperglycemic diagnosis Education plan Hypoglycemia protocol Guidance for transitions (linked protocols) Patients should have an established glycemic target. Appropriate nutrition should be provided. A consistent carbohydrate diet is preferred for the eating patient. An A1c level from the last 30 days should be available to guide management. Each patient should be classified as to specific hyperglycemic related diagnosis. Education for diabetes and hyperglycemia should be reliably provided. Glucose monitoring should be coordinated with the delivery of nutrition and insulin. Insulin is the preferred agent for controlling inpatient hyperglycemia. Anticipatory, physiologic �basal-bolus plus correction dose� insulin regimens are preferred (sliding scale insulin regimens are to be avoided). Suggested insulin starting doses and adjustment strategies should be incorporated into institutional protocols and order sets. Institutional guidance for different nutritional circumstances and special situations should be provided in protocols and educational efforts. Hypoglycemia management protocols should be integrated into all order sets involving anti-hyperglycemic agents. Discharge planning should be tailored to individual patient needs. Guidance for transitions should be included in protocols and order sets Patients should have an established glycemic target. Appropriate nutrition should be provided. A consistent carbohydrate diet is preferred for the eating patient. An A1c level from the last 30 days should be available to guide management. Each patient should be classified as to specific hyperglycemic related diagnosis. Education for diabetes and hyperglycemia should be reliably provided. Glucose monitoring should be coordinated with the delivery of nutrition and insulin. Insulin is the preferred agent for controlling inpatient hyperglycemia. Anticipatory, physiologic �basal-bolus plus correction dose� insulin regimens are preferred (sliding scale insulin regimens are to be avoided). Suggested insulin starting doses and adjustment strategies should be incorporated into institutional protocols and order sets. Institutional guidance for different nutritional circumstances and special situations should be provided in protocols and educational efforts. Hypoglycemia management protocols should be integrated into all order sets involving anti-hyperglycemic agents. Discharge planning should be tailored to individual patient needs. Guidance for transitions should be included in protocols and order sets

6. Integrate Best Practice into protocols, order sets, documentation Coordinated insulin / nutrition / monitoring. Insulin preferred - DC oral agents Basal / Nutrition / Correction terminology Dosing adjustment guidance Specific regimens for different situations NPO Eating Tube feeds Steroids, etc Patients should have an established glycemic target. Appropriate nutrition should be provided. A consistent carbohydrate diet is preferred for the eating patient. An A1c level from the last 30 days should be available to guide management. Each patient should be classified as to specific hyperglycemic related diagnosis. Education for diabetes and hyperglycemia should be reliably provided. Glucose monitoring should be coordinated with the delivery of nutrition and insulin. Insulin is the preferred agent for controlling inpatient hyperglycemia. Anticipatory, physiologic �basal-bolus plus correction dose� insulin regimens are preferred (sliding scale insulin regimens are to be avoided). Suggested insulin starting doses and adjustment strategies should be incorporated into institutional protocols and order sets. Institutional guidance for different nutritional circumstances and special situations should be provided in protocols and educational efforts. Hypoglycemia management protocols should be integrated into all order sets involving anti-hyperglycemic agents. Discharge planning should be tailored to individual patient needs. Guidance for transitions should be included in protocols and order sets Patients should have an established glycemic target. Appropriate nutrition should be provided. A consistent carbohydrate diet is preferred for the eating patient. An A1c level from the last 30 days should be available to guide management. Each patient should be classified as to specific hyperglycemic related diagnosis. Education for diabetes and hyperglycemia should be reliably provided. Glucose monitoring should be coordinated with the delivery of nutrition and insulin. Insulin is the preferred agent for controlling inpatient hyperglycemia. Anticipatory, physiologic �basal-bolus plus correction dose� insulin regimens are preferred (sliding scale insulin regimens are to be avoided). Suggested insulin starting doses and adjustment strategies should be incorporated into institutional protocols and order sets. Institutional guidance for different nutritional circumstances and special situations should be provided in protocols and educational efforts. Hypoglycemia management protocols should be integrated into all order sets involving anti-hyperglycemic agents. Discharge planning should be tailored to individual patient needs. Guidance for transitions should be included in protocols and order sets

7. Problems with Oral Agents in the Hospital Sulfonylureas (e.g., glyburide, glipizide, etc.) Hypoglycemia (long acting) ? CAD Metformin Lactic acidosis risk Renal insufficiency, hypotension, heart failure) Gastrointestinal Nausea, abdominal pain, diarrhea Thiazolidinediones (TZDs or �glitazones�) (e.g., rosiglitazone) Possible liver toxicity Fluid overload, heart failure Inability to titrate (very slow onset of action)

8. Physiologic Insulin Secretion:Basal-Bolus Concept When we consider glucose control, we need to focus on both postprandial and basal requirements. This slide illustrates the normal diurnal physiologic response, which highlights the need for both basal and meal insulin. Meal-insulin release occurs in response to nutrient ingestion. Basal insulin is continually secreted over a 24-hour period to maintain homeostasis in the body energy requirements and balance. The �normal� human adult secretes about 25-30 units of insulin a day. As you can see, about � of this is in �BASAL� insulin. You can also see that a �normal� patient would likely not exceed PG = 150 mg/dL, even after a meal. These ambient glucose levels (euglycemia) are reflected in a �normal� GHbA1c range of 4.5-6.5% in the USA. NOTE � if you take a random BG (about 15-20% less in value than PG) and it is >130mg/dL, it would be suspect. I will show you what I mean in later slides, but keep this in mind. - If the patient just ate, or it he/she ate 2-3 hours before, it would make a difference in how you may advise him/her concerning seeking medical advise. (Refer to OGTT � Oral Glucose Tolerance Test � data) In the past, we have had to make due with various insulin formulations that did not have adequate pharmacokinetics to duplicate these profiles. However, within the past few years, new insulin analogs have been developed, which provide more physiologic profiles. When we consider glucose control, we need to focus on both postprandial and basal requirements. This slide illustrates the normal diurnal physiologic response, which highlights the need for both basal and meal insulin. Meal-insulin release occurs in response to nutrient ingestion. Basal insulin is continually secreted over a 24-hour period to maintain homeostasis in the body energy requirements and balance. The �normal� human adult secretes about 25-30 units of insulin a day. As you can see, about � of this is in �BASAL� insulin. You can also see that a �normal� patient would likely not exceed PG = 150 mg/dL, even after a meal. These ambient glucose levels (euglycemia) are reflected in a �normal� GHbA1c range of 4.5-6.5% in the USA. NOTE � if you take a random BG (about 15-20% less in value than PG) and it is >130mg/dL, it would be suspect. I will show you what I mean in later slides, but keep this in mind. - If the patient just ate, or it he/she ate 2-3 hours before, it would make a difference in how you may advise him/her concerning seeking medical advise. (Refer to OGTT � Oral Glucose Tolerance Test � data) In the past, we have had to make due with various insulin formulations that did not have adequate pharmacokinetics to duplicate these profiles. However, within the past few years, new insulin analogs have been developed, which provide more physiologic profiles.

9. Which Patients Need Basal Insulin in the Hospital? �Insulin-deficient� patients should always have basal insulin (even NPO): Type 1 DM or DKA, pancreatic insufficiency A history of type 2 DM for 10 years or more On any insulin for 5 years or more Wide fluctuations of glucose values Preprandial glucose > ?130, 150 mg/dL Any glucose > 180 mg/dL

10. Constructing a Profile for Scheduled Subcutaneous Insulin �.

11. SHM Glycemic Control Task ForcePreferred Insulin Regimens See handout In interest of standardization, narrow down choices. Eliminating other acceptable choices, but also many unacceptable ones! Allow variation, while encouraging standardization

12. Common Features Increasing Risk of Hypoglycemia in an Inpatient Setting Malnutrition and low body weight Chronic renal failure Decreased oral intake, failure to provide nutrition or dextrose infusion Advanced age Liver disease Beta-blockers Iatrogenic Risk Factors: SSI, distractions, poor regimens: disconnect between testing, administration of insulin, and nutrition

15. Calculating Insulin Dosage (Total Daily Dose) Calculate from insulin infusion amount Recent steady state hourly rate x 20, for example Add up insulins taken at home, adjust for glycemic control and other factors Calculate from weight, body habitus, other factors

16. Calculate starting total daily dose (TDD) 0.3 units/kg/day (hypoglycemia risk factors, na�ve patient) 0.4 units/kg/day (conservative for most patients) 0.5 � 0.6 units/kg/day (overweight to obese) Adjust TDD up or down based on Past response to insulin Presence of hyperglycemia inducing agents, stress This Is very conservative and safe (adjust up as needed) Basal insulin = 40-50% of TDD Glargine q HS or q AM, detemir in 1 or 2 doses Goal: FBS and pre-meal glucose = 80-110 mg/dL

17. Case # 1: Initiating Subcutaneous Insulin in an obese patient eating regular meals 56 year old man admitted with diabetic foot infection, eating regular meals. Obese, weighs 100 kg Home regimen 2 OHG�s and 20 units of NPH q HS Baseline Control: HbA1c of 10, POC glucose in ED 240 mg/dL What are your initial orders for insulin? What change would you make if he had to go to the OR the next morning?

19. Case #1: Solutions for Obese, eating patient Accuchecks AC and HS TDD: 100 kg x 0.6 units/kg/day = 60 units Glargine (Lantus) Alternative Basal: Glargine 30 units q HS Nutritional: Lispro 10 units q ac Correction: Lispro per scale q ac and HS For NPO p MN and OR the next AM Hold nutritional dose, continue adjustment dose Give the full dose of Glargine q HS: No change. 2 points if basal, 1 point if nutritional, 1 point if correction used and c/w nutritional, 2 points in TDD between 30 and 70, 1 point if AC and HS monitoring, extra credit of nutritional insulin is lispro2 points if basal, 1 point if nutritional, 1 point if correction used and c/w nutritional, 2 points in TDD between 30 and 70, 1 point if AC and HS monitoring, extra credit of nutritional insulin is lispro

20. Adjust, Adjust, Adjust If glucoses going < 70 mg / dL, use 80% of TDD as next days TDD If glucose readings > 150 and no hypoglycemic values, use 120% of yesterday�s total as new TDD (or 130%, depending on the uniformity and degree of poor control)

21. Case # 2: Patient in IMU on Continuous TF 65 year old you are seeing for the first time in the IMU, no outpatient history available except �on insulin�. Glucose > 200 in ED, HbA1C pending. 80 kg overweight woman started on continuous TF yesterday (HD#3), with serum glucose in 200-250 mg/dL range What would you order?

22. TPN or Continuous Tube Feedings

23. Continuous Tube Feeding Insulin Regimen

24. Case #2 Solutions in a patient on continuous TF or TPN Accuchecks q 6 hours TDD is 0.5 units/kg/day x 80 kg = 40 units Basal: Glargine 16 units q hs (or q am) Nutritional: 6 units regular insulin q 6 h Correction: regular insulin q 6 h per scale Patients being started on TPN do better with separate insulin infusions initially (with y � connector) to find dose. Conversion then can be made to insulin in TPN (80% of TDD), or subcutaneous regimen. Accuchecks q 6 h 1 point, TDD between 24 and 54 units 2 points, Basal insulin use 2 points, nutritional insulin use 1 point, correction doses 1 point, EC for using regular insulin in a q 6 h setting.Alternative scoring for insulin infusion.Accuchecks q 6 h 1 point, TDD between 24 and 54 units 2 points, Basal insulin use 2 points, nutritional insulin use 1 point, correction doses 1 point, EC for using regular insulin in a q 6 h setting.Alternative scoring for insulin infusion.

25. Case #3: Transition from IV to subcutaneous insulin 60 yo man with DM 2, well controlled in ICU on insulin infusion and continuous TF at 40 ml/hour. Insulin Infusion rate 80 units in the last 24 hours, 3 units / hour over last 6 hours. Prior to hospitalization, baseline HbA1c was 8.7 on 40 units of 70/30 insulin per day and OHGs. Plan: Transfer to ward, continue enteral nutrition How do you transition this patient to a subcutaneous insulin regimen?

26. Stepwise approach to moving from IV to SC insulin Calculate how much IV insulin the patient has been requiring. Modify down for safety cushion. Was this insulin supplying Basal requirements, or Basal and Nutritional requirements? Translate into the subcutaneous regimen. Consider any nutritional changes that may be implemented at the time of the transition off of the drip Make sure SC insulin is given before discontinuation of the IV insulin The patient in this example is getting insulin infusion and changing for a change to a subcutaneous regimen. Calculate how much IV insulin the patient has been requiring. It should be easy to discover how much insulin the patient has been getting in the hospital. This can be accomplished by adding up the amount of IV insulin that was administered over the previous day. However, in some cases, the patient may not have been stable on an insulin infusion for a full 24 hour period before they are switched to a subcutaneous program. In these cases, one might estimate the stable hourly rate during a shorter period of stability, and multiply that hourly rate by 20 to arrive at a conservative estimate of the insulin needed over that day. Patients who are receiving very low doses of insulin by the insulin infusion (e.g. < 0.5 units/hr) may not need SC insulin, unless they are known to be insulin deficient (e.g. type 1 diabetes). These patients might simply be monitored and given correctional insulin, if needed. Recognize which component of physiologic insulin the IV insulin represents, and translate that to a SC regimen. Intravenous insulin may represent basal insulin (if the patient was not receiving any nutrition), basal and nutritional insulin (if the patient was receiving full nutrition), or basal insulin plus some portion of nutritional insulin (if the patient was getting only part of their total daily nutrition). In this case, the patient is receiving full dose enteral nutrition, so the insulin that the patient has been receiving is, in fact, representative of both basal and nutritional insulin (= TDD while on tube feedings). Once the SC regimen is initiated, careful monitoring is necessary. Patients who are recovering from a major surgery or a severe illness often have a gradual decline in their total insulin requirement as their clinical condition improves. Assess any nutritional changes that may be occurring at the same time. The switch from IV insulin to SC insulin often occurs concomitantly with a change in diet. When that is the case, care must be taken to assure that the patient�s insulin program remains appropriate. In this case, the patient is continuing on enteral nutrition. If he was also changing from enteral nutrition to a po diet status, a reduction in his nutritional insulin would be wise until you were confident in his po intake (discussed later). Make sure SC insulin is given before discontinuation of the IV insulin. Since the duration of action of IV insulin is on the order of 7 minutes, discontinuation of insulin via the IV route necessitates the pre-emptive delivery of SC insulin before the IV insulin is stopped. If this does not occur, the patient may become rapidly hyperglycemic again or, if a type 1 diabetic, rapidly experience DKA. It is recommended that IV insulin be continued until the subcutaneous regimen is able to provide appropriate, continuous levels of insulin. It has been suggested that an insulin infusion should not be stopped for at least 1 hour after the SC delivery of rapid-acting or regular insulin, and at least 2 hours after the SC delivery of intermediate- or long-acting insulin. If the insulin infusion is to be stopped at a time when basal insulin is not scheduled to be given, some have recommended altering the intended insulin regimen to assure continuous insulin is provided. The patient in this example is getting insulin infusion and changing for a change to a subcutaneous regimen. Calculate how much IV insulin the patient has been requiring. It should be easy to discover how much insulin the patient has been getting in the hospital. This can be accomplished by adding up the amount of IV insulin that was administered over the previous day. However, in some cases, the patient may not have been stable on an insulin infusion for a full 24 hour period before they are switched to a subcutaneous program. In these cases, one might estimate the stable hourly rate during a shorter period of stability, and multiply that hourly rate by 20 to arrive at a conservative estimate of the insulin needed over that day. Patients who are receiving very low doses of insulin by the insulin infusion (e.g. < 0.5 units/hr) may not need SC insulin, unless they are known to be insulin deficient (e.g. type 1 diabetes). These patients might simply be monitored and given correctional insulin, if needed. Recognize which component of physiologic insulin the IV insulin represents, and translate that to a SC regimen. Intravenous insulin may represent basal insulin (if the patient was not receiving any nutrition), basal and nutritional insulin (if the patient was receiving full nutrition), or basal insulin plus some portion of nutritional insulin (if the patient was getting only part of their total daily nutrition). In this case, the patient is receiving full dose enteral nutrition, so the insulin that the patient has been receiving is, in fact, representative of both basal and nutritional insulin (= TDD while on tube feedings). Once the SC regimen is initiated, careful monitoring is necessary. Patients who are recovering from a major surgery or a severe illness often have a gradual decline in their total insulin requirement as their clinical condition improves. Assess any nutritional changes that may be occurring at the same time. The switch from IV insulin to SC insulin often occurs concomitantly with a change in diet. When that is the case, care must be taken to assure that the patient�s insulin program remains appropriate. In this case, the patient is continuing on enteral nutrition. If he was also changing from enteral nutrition to a po diet status, a reduction in his nutritional insulin would be wise until you were confident in his po intake (discussed later). Make sure SC insulin is given before discontinuation of the IV insulin. Since the duration of action of IV insulin is on the order of 7 minutes, discontinuation of insulin via the IV route necessitates the pre-emptive delivery of SC insulin before the IV insulin is stopped. If this does not occur, the patient may become rapidly hyperglycemic again or, if a type 1 diabetic, rapidly experience DKA. It is recommended that IV insulin be continued until the subcutaneous regimen is able to provide appropriate, continuous levels of insulin. It has been suggested that an insulin infusion should not be stopped for at least 1 hour after the SC delivery of rapid-acting or regular insulin, and at least 2 hours after the SC delivery of intermediate- or long-acting insulin. If the insulin infusion is to be stopped at a time when basal insulin is not scheduled to be given, some have recommended altering the intended insulin regimen to assure continuous insulin is provided.

27. Case: Transition to subcutaneous insulin(enteral nutrition to continue) Safe Estimate of 24 hour requirement: 3 units / hour x 20 = 60 units 60 units represents the TDD: Basal and nutritional insulin 50:50 Rule Example Glargine 30 units = Basal Regular 7 units q 6 h = Nutritional Correction dose of regular insulin also given along with nutritional dose as needed. Glargine / Nutritional should be given BEFORE IV insulin stopped This is one example at calculating a safe starting dose for subcutaneous insulin. Alternately, some estimate of the 24 hour requirement could be multiplied by a factor of .75 or .80 to arrive at an estimate. The 60 units / day estimate gains credence when one considers the patient�s outpatient regimen (he was poorly controlled on 40 units of insulin per day and oral hyopglycemics). Since 60 units is the requirement for basal and nutritional needs, we need to distribute this TDD in a rational way. The 50:50 rule is generally a good way to estimate how this TDD should be divided up into basal and nutritional requirements. Using longer acting basal insulins like glargine, while not proven superior in the hospital, is certainly more physiologic, and can allow one to continue the same dose of basal insulin whether the pt is NPO or not. The nutritional insulin can be regular q 6 hours as shown here. Alternatively, a RAA insulin q 4 hours would also be appropriate. This is one example at calculating a safe starting dose for subcutaneous insulin. Alternately, some estimate of the 24 hour requirement could be multiplied by a factor of .75 or .80 to arrive at an estimate. The 60 units / day estimate gains credence when one considers the patient�s outpatient regimen (he was poorly controlled on 40 units of insulin per day and oral hyopglycemics). Since 60 units is the requirement for basal and nutritional needs, we need to distribute this TDD in a rational way. The 50:50 rule is generally a good way to estimate how this TDD should be divided up into basal and nutritional requirements. Using longer acting basal insulins like glargine, while not proven superior in the hospital, is certainly more physiologic, and can allow one to continue the same dose of basal insulin whether the pt is NPO or not. The nutritional insulin can be regular q 6 hours as shown here. Alternatively, a RAA insulin q 4 hours would also be appropriate.

28. What if??? Enteral to PO Instead of continuing enteral nutrition on the floor, you opt to stop enteral nutrition and start patient on a mechanical soft diet? Glargine 30 units = Basal RAA 10 units q AC = Nutritional / Prandial (IF you expect them to eat a full meal! ) If po intake suspect at first, use CHO counting, or empirically reduce nutritional RAA dose and give the dose just AFTER the meal instead of just BEFORE the meal. CORRECTION dose RAA insulin also needed.

29. Have a Discharge PlanTailored to Patient! Diabetes and insulin education, survival skills: START EARLY and repeat Follow up and community resources Covered by insurance Patient and family can understand Reconcile medications Language, health literacy, and cultural barriers Use HbA1c Insulin requirement may decrease post discharge