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![BACKGROUND
• Glycemic control (GC) in critically ill patients became a
topic of interest in 2001 after a landmark trial by Van den
Berghe et al. determined a significant mortality benefit in
patients treated with intensive insulin therapy
(maintenance of blood glucose [BG] between 80 and 100
mg/dL).1
• However, more recent randomized controlled trials in
various intensive care unit (ICU) settings demonstrate
conflicting results.
3](https://image.slidesharecdn.com/insulininicu2-171122205619/75/Insulin-in-icu-2-3-2048.jpg)
Uploaded byDr.Tarek Sabry
Insulin in icu 2
This document provides guidelines for managing hyperglycemia in ICU patients using insulin therapy. It recommends a target blood glucose range of 100-150 mg/dL. The guidelines describe different types of insulin, including rapid, short, intermediate and long-acting varieties. It presents a protocol for intravenous insulin therapy that involves calculating initial bolus and infusion rates based on the patient's starting blood glucose level. The protocol provides guidance on adjusting the infusion rate based on hourly blood glucose monitoring and includes steps to avoid and treat hypoglycemia.
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Insulin in icu 2
- 1. Management of Hyperglycemia inthe ICU BY Dr.Tarek Sabri (intensivist) Fujairah Hospital U.A.E 1
- 2. Items • Background ofinsulin therapy in ICU • Effect of hyperglycemia on critically ill patients. • Last Recommendations for insulin therapy in ICU • Types of insulin. • Suggested protocol for insulin therapy in ICU. • Transition from IV insulin to S.C regimen. • How to avoid Hypoglycemia and how to mange it. • Summary 2
- 3. BACKGROUND • Glycemic control(GC) in critically ill patients became a topic of interest in 2001 after a landmark trial by Van den Berghe et al. determined a significant mortality benefit in patients treated with intensive insulin therapy (maintenance of blood glucose [BG] between 80 and 100 mg/dL).1 • However, more recent randomized controlled trials in various intensive care unit (ICU) settings demonstrate conflicting results. 3
- 4. Distribution of Patient-Day-Weighted MeanPOC-BG Values for ICU 4 ~12 million BG readings from 653,359 ICU patients; mean POC-BG: 167 mg/dL. Swanson CM, et al. Endocr Pract. 2011;17:853-861.
- 5. MortalityRate(%) Mean Glucose Value(mg/dL) N=1826 ICU patients. Krinsley JS. Mayo Clin Proc. 2003;78:1471-1478. 0 5 10 15 20 25 30 35 40 45 80-99 100-119 120-139 140-159 160-179 180-199 200-249 250-299 >300 0 5 10 15 20 25 30 35 40 45 0 5 10 15 20 25 30 35 40 45 Hyperglycemia and Mortality in the Medical Intensive Care Unit 5
- 6. Hyperglycemia: An IndependentMarker of ICU Mortality 6Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978-982. In-hospitalMortalityRate(%) New Hyperglycemia Known Diabetes Normoglycemia P<0.01 P<0.01
- 7. Stress Hormones cortisol,epinephrine Glucose Production Lipolysis FFAs FFAs + Glucose Uptake Illness Glucose Fatty Acids Illness Leads to Stress Hyperglycemia 7
- 8. Stress Hyperglycemia Exacerbates Illness 8 Stress Hormones cortisol, epinephrine Glucose Production Lipolysis FFAs FFAs + Glucose Uptake Glucose Fatty Acids Hemodynamic insult Electrolyte losses Oxidative stress Myocardial injury Hypercoagulability Altered immunity Wound healing Inflammation Endothelial function Illness
- 9. • Although GCis beneficial in this patient population, the extent of GC which can be safely achieved without increased risk for hypoglycemia (BG ≤ 70 mg/dL) has not been established. • A clinical practice guideline was published in December 2012 by the Society of Critical Care Medicine to help clinicians achieve GC that is considered safe and effective without increasing the risk of significant hypoglycemia. 9
- 10. • This newguideline recommends a target range of 100 to 150 mg/dL for most adult critically ill patients, which differs from the previously published American Association of Clinical Endocrinologists and the American Diabetes Association recommendations that BG should be maintained between 140 and 180 mg/dL in critically ill patients. • The focus of this guideline is the safe use of insulin infusions in adult ICU patients. 10
- 11. RECOMMENDATIONS • The Gradingof Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the quality of evidence and strength of recommendation. • Recommendations are classified as strong (Grade 1) or weak (Grade 2). Strong recommendations are listed as “recommendations” and weak recommendations as “suggestions”. There are 18 clinical practice questions addressed in the guideline which are summarized below. 11
- 12. RECOMMENDATIONS The current literaturesupporting insulin infusion therapy in adult ICU patients is not conclusive with regard to the appropriate extent of GC; therefore, many of the recommendations in these new guidelines are weak recommendations. After the authors’ review of the literature, it is suggested that a BG level of ≥ 150 mg/dL trigger initiation of insulin therapy titrated to maintain BG levels < 150 mg/dL and absolutely < 180 mg/dL 12
- 13. RECOMMENDATIONS Monitoring system shouldbe implemented to avoid and detect hypoglycemia and glycemic variability. For patients with brain injury, a more stringent goal of avoiding BG ≤ 100 mg/dL is described. Monitoring of BG should occur every 1 to 2 hours for most patients. Finally, the guidelines encourage implementation of a standard insulin infusion protocol in the ICUs to promote the safe and effective use of insulin infusion therapy. 13
- 14. Insulin types andtheir action Onset: 5 to 15 mins Peak: 1 to 3 hours Duration: 5 hours Drug name Brand name Manufacturer Insulin Aspart Novorapid Novo Nordisk Insulin Lispro Humalog Eli Lilly Insulin Glulisine Apidra Sanofi-Aventis 14 Ultra short acting analogues •Should be injected immediately before eating •Clear appearance
- 15. Insulin types andtheir action Onset: 30 mins Peak: 2.5 to 5 hour Duration: 8 hours Drug name Brand name Manufacturer Insulin neutral (regular) Actrapid Novo Nordisk Insulin neutral (regular) Humulin R Eli Lilly 15 Short acting insulins •Should be injected half an hour before a meal •Clear appearance
- 16. Insulin types andtheir action Onset: 1.5 hrs Peak: 4 to 12 hrs Duration: 12 to 16 ( up to 24hrs) Drug name Brand name Manufacturer Isophane Protaphane Novo Nordisk Isophane (NPH) Lantus Sanofi-Aventis 16 Intermediate acting insulins •Does not need to be injected with a meal •Cloudy in appearance •Needs to be gently shaken before every use
- 17. Insulin types andtheir action Drug name Brand name Manufacturer Insulin determir Levemir Novo Nordisk Insulin glargine Lantus Sanofi-Aventis 17 Long acting analogue insulins •Clear in appearance •Does not need to be injected with a meal
- 18. Insulin types andtheir action Onset: varies Peak: varies Duration: varies Drug name Brand name Manufacturer 25 per cent insulin lispro/ 75 per cent insulin lispro protamine suspension Humalog Mix 25 Novo Nordisk 50 per cent insulin lispro/ 50 per cent insulin lispro protamine suspension Humalog Mix 50 Eli Lilly 18 Pre-mixed insulins Cloudy in appearance Should be gently shaken before every use Humalog Mix and NovoMix need to be injected immediately before a meal Mixtard and Humulin should be injected half an hour before a meal
- 19. Insulin types andtheir action Onset: varies Peak: varies Duration: varies Drug name Brand name Manufacturer 30 per cent insulin aspart/ 70 per cent insulin aspart protamine supension NovoMix 30 Novo Nordisk 30 per cent insulin neutral (regular) 70 per cent isophane Humulin 30/70 Eli Lilly 30 per cent insulin neutral (regular) 70 per cent isophane Mixtard 30/70 Novo Nordisk 50 per cent insulin neutral (regular) 50 per cent isophane Mixtard 50/50 Novo Nordisk 19 Pre-mixed insulins
- 20. Indications for IVInsulin Therapy • Diabetic ketoacidosis • Nonketotic hyperosmolar state • Critical care illness (surgical, medical) • Postcardiac surgery • Myocardial infarction or cardiogenic shock • NPO status in type 1 diabetes • Labor and delivery • Glucose exacerbated by high-dose glucocorticoid therapy • Perioperative period • After organ transplant • Total parenteral nutrition therapy 20 ACE Task Force on Inpatient Diabetes and Metabolic Control. Endocr Pract. 2004;10:77-82.
- 21. Components of IVInsulin Therapy • Concentrations should be standardized throughout the hospital – Regular insulin in concentrations of 1 U/mL or 0.5 U/mL – Infusion controller adjustable in 0.5-U doses • Accurate bedside blood glucose monitoring done hourly (every 2 hours if stable) • Potassium should be monitored and given if necessary 21 Clement S, et al. Diabetes Care. 2004;27:553-591.
- 22. ICU Insulin InfusionProtocol For Adults • The following protocol is intended for use in hyperglycemic adult patients in ICU, in keeping with last glucose control guidelines from international organizations . • It should Not be used in diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) ,AS these patients may required higher insulin doses, IV dextrose at some point , and important adjunctive therapies for there fluid/acid-base/electrolyte status. • addressed by this protocol , the MD must be contacted for further assessment and further orders 22
- 23. ICU Insulin InfusionProtocol For Adults • In any patient with blood glucose > 500 mg /dL,the initial orders should be carefully reviewed with MD, since a higher initial insulin dose and additional monitoring therapy may be required. • If the patient response to insulin infusion at any time unusual, or unexpected , or if any situation arises that is not adequately 23
- 24. ICU Insulin InfusionProtocol For Adults 24 Insulin infusion: Mix 1 U regular human insulin per 1 mL 0.9% NaCl Administer via infusion pump in increments of 0.5 U/h Blood glucose target range: 120-160 mg/dL Use glucose meter to monitor blood glucose hourly Bolus and initial infusion rate: Divide initial BG by 100, round to nearest 0.5 U for bolus and initial infusion rates Example: Initial BG = 325 mg/dL: 325/100 = 3.25, round up to 3.5: IV bolus = 3.5 U + start infusion at 3.5 U/h Subsequent rate adjustments: Changes in infusion rate are determined by the current infusion rate and the hourly rate of change from the prior BG level Shetty S, et al. Endocr Pract. 2012;18:363-370.
- 25. Ministry of Health FujairahMedical Zone Fujairah Hospital ﻟﺼﺤـﺔ اةرازو ﻟﻄﺒﯿـﺔ اه ﻟﻔﺠﯿﺮ ﻣﻨﻄﻘـﺔا ﻟﻔﺠﯿﺮه ﻣﺴﺘﺸﻔﻰا Fujairah Hospital ICU Insulin Infusion Protocol for Adults The following protocol is intended for use in hyperglycemic adult patients in the ICU, in keeping with the latest glucose guidelines from international organizations. It should NOT be used in diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS), as these patients may require higher initial insulin doses, IV dextrose at some point, and important adjunctive therapies for their fluid/acid-base/electrolyte status. In any patient with BG>500mg/dl, the initial orders should also be carefully reviewed with the MD, since a higher initial insulin dose and additional monitoring/theraphy may be rquired. If the patient’s response to the insulin infusion is at any time unusual or unexpected, or if any situation arises that is not adequately addressed by this protocol, the MD must be contacted for assessment and further orders. Getting Started PATIENT SELECTION: Begin this protocolin any ICU Patient with more than 2 BGs>150mg/dlwho is not expectedto rapidly normalizetheir1.) glycemic status. Patients who are eating(see#9below);transferring out of ICU imminently(<24hrs); or pre-terminalor being consideredfor DNR are generallynot appropriatecandidatesfor this protol. TARGET BLOOD GLUCOSE(BG)RANGE: 120 – 160 1MM20- 160mg/dl 3.) ORDERS: MD order required for use in the ICU.2.) 4.) 5.) 7.) INSULIN INFUSION SOLUTION: Obtain from pharmacy(1unit Regular Human Insulin/ 1 cc 0.9% NaCI). PRIMING: Beforeconnecting,flush 20 cc infusionthrough all tubing. 6.)ADMINISTRATION: Via infusionpump in 0.5 units/hr increments. BOLUS & INITIAL INFUSION RATE: Divide initial BG level by 100, then round to nearest 0.5 units for bolus AND initial infusionrate. Examples:1.) Initial BG = 325mg/dl: 325 ÷ 100 =3.25,round ↑ to 3.5: IV bolus 3.5 units + start infusion @ 3.5 units/hr 2.) Initial BG = 274 mg/dl: 274 ÷ 100 = 2.74, round ↓ to 2.5: IV bolus 2.5 units + start infusion@ 2.5 units/hr 8.) CAUTION: If enteral/parenteral(TPN,PPN,Tube feeds)nutritionabruptly stopped, reduceinfusion rate by 50%. 9.) Patients requiring IV insulin are usually NPO. In the rare patient who is eating, considergiving SC Aspartto ‘cover’ the meal (administer 1 unit/ 15 grams carbohydrates consumed(usualdose 3-6 units.) In this circumstancedon’t increase infusion rate during the first 3 hrs. 10.) Patients with TIDM, insulin-requiringT2DM, and those requiring>1unit/hr should be transitionedto SC insulin prior to dischargefrom ICU. BG Monitoring While on infusion, use glucosemeter to check BG hourly. Once stable (3 consecutivevalues in target range), may reducechecks to q 2 hr. If stable For 12-24 hrs, may space checks to q 4 hr. Resumehourly checks until stable again if: any BG out of range; any chances in insulininfusionrate: any Significantchangein clinical condition; initiation/discontinuation of steroids, pressors,TPN/PPN/tubefeeds, dialysis, CVVH, or CAVH. In patients Who are vasoconstricted/hypotensive, capillary BG(i.e, fingersticks)may be inaccurate;venous or arterial bloodis preferredin this setting. Adjusting Infusion Rate If BG<50mg/dl: DDC INSULIN INFUSION N& administer 1 amp (25 g) D50 IV; recheck BG q 15 minutes until ≥90 mg/dl. → Then, recheck BG q 1 hr; when ≥ 140 mg/dl, wait 30min, restart insulin at 50% of most recent rate. If BG 50-74 MG/dl: DC INSULIN INFUSION U& administer ½ Amp (12.5g) D50IV; recheck BG q 15 minutes until≥90mg/dl. →Then, recheck BG q 1 hr: when≥140mg/dl,wait 30 min, then restartinfusionat 50% of most recent rate. If BG 75-99mg/dl: DC INSULIN INFUSION URecheck BG w 15 minutes until BG reachesor remains≥90mg/dl. --→ Then, recheck BG q 1 hr; when≥ 140 mg/dl, wait 30min,then restartinfusion at 75% of most recent rate.
- 26. Ministry of Health FujairahMedical Zone Fujairah Hospital ﻟﺼﺤـﺔ اةرازو ﻟﻄﺒﯿـﺔ اه ﻟﻔﺠﯿﺮ ﻣﻨﻄﻘـﺔا ﻟﻔﺠﯿﺮه ﻣﺴﺘﺸﻔﻰا ICU Insulin Infusion Protocol Determinethe CURRENT BG LEVEL – identifies a COLUMN in the table: Target BG: 120-160 STEP 1: Begin IV insulin: BG ÷ 100 = U/hr STEP 2: Determine the RATE OF CHANGE from the prior BG level – identifies a CELL in the table- Then move right for INSTRUCTIONS: (Note: If the last BG was measured 2 or more hrs before the current BG, CALCULATE THE HOURLY RATE OF CHANGE. Example: If the BG at 2PM was 150mg/Dl and the BG at 4PM is 120 mg/dl, the total change over 2 hours is -30mg/dl;however, the hourly Change is -30mg/dl ÷ 2 hours =-15mg/dl/hr) STEP 3: CHANGES IN INFUSION RATE*(“#”) Are determined by the current rate: (Units /hr) *Depending on the clinical circumstances infusion rates typically range between 2-10 units/hr. Doses in excess of units/hr are unusual and if required the responsible MD should be notified to explore Current Rate (Units/hr) # =Rate Change (Units/hr) 2# = 2X Rate Cahnge < 3.0 0.5 1 3.0 – 6.0 1 2 6.5 -9.5 1.5 3 10.0-14.5 2 4 15-19.5 3* 6* ! 20* 4* 8* D/C INSULIN INFUSION; %BG in 15 min to be sure !90 mg/dl. Then recheck BG Q 1 hr; when ! 140 mg/dl, Restart infusion @ 75% of Most recent rate. BG 100-119mg/dL BG 120-159 mg/dL BG 160-199 mg/dL BG ! 200mg/dL INSTRUCTIONS* BG” by >60mg/dl/hr BG” “INFUSION BY “2#” BG “ by>40 mg/dl/hr BG” by 1-60mg/dl/hr OR BG UNCHANGE BG UNCHANGED OR BG↓ by 1-20mg/dl/hr “INFUSION BY “#” BG” BG” by 1-40mg/dl/hr, BG UNCHANGED, OR BG↓ by 1-20 mg/dl/hr BG ↓ by 1-40 mg/dl/hr BG↓ by 21-60mg/dl/hr NO INFUSION CHANGE BG UNCHANGED OR BG↓ by 1-20mg/dl/hr BG↓ by 21-40mg/dl/hr BG↓ by 41-60mg/dl/hr BG↓ by 61-80mg/dl/hr ↓ INFUSION by “#” BG↓ by >20mg/dl/hr See below BG↓ by >40mg/dl/hr BG↓ by >60mg/dl/hr BG↓ by >80mg/dl/hr HOLD x 30min, then ↓ INFUSION by “2#” BG 100-119 mg/dL BG 120-159 mg/dL BG 160-199 mg/dL BG ! 200mg/dL
- 27. TRANSITION FROM IVTO SC INSULIN 27
- 28. Considerations for TransitionFrom IV to SC Insulin • Which patients on IV insulin will need a transition to scheduled SC insulin? – Type 1 DM – Type 2 DM on insulin prior to admission – Type 2 DM (or new hyperglycemia) requiring ≥2 units/hour of insulin 28Umpierrez G, et al. J Clin Endocrinol Metab. 2012;97:16-38.
- 29. Transition From IVInsulin to SC Insulin • IV insulin should be transitioned to SC basal bolus insulin therapy – When patient begins to eat and BG levels are stable • Because of short half-life of IV insulin, SC basal insulin should be administered at least 1-2 hours prior to discontinuing the drip 29Umpierrez G, et al. J Clin Endocrinol Metab. 2012;97:16-38.
- 30. Additional Questions toConsider When Converting to SC Insulin • Is the patient eating? If so, what and when? • What are the concomitant therapies? – Glucocorticoids? – Inotropes? – Vasoconstrictors? • Will resolution of the illness(es) or change in concomitant therapies reduce insulin needs? 30
- 31. Calculating the SCInsulin Dose • Establish the 24-hour insulin requirement by extrapolating from the average intravenous insulin dose required over the previous 6-8 hours (if stable) • Take 60%-80% of the total daily dose (TDD) – Give one-half as an intermediate-acting or long-acting insulin for basal coverage – Give other half as a short-acting or rapid-acting insulin in divided doses before meal 31Umpierrez G, et al. J Clin Endocrinol Metab. 2012;97:16-38.
- 32. Proposed Predictors forSuccessful Transition From IV Insulin Infusion to SC Insulin Therapy More likely to successfully transition without a loss of glycemic control • Underwent uncomplicated CABG and/or valve surgery and discharged from ICU extubated • Taking liquids/regular meals • Following house/ADA diet • Stable renal function • Observed for 6-8 h before breakfast to determine basal insulin requirement • With type 2 diabetes or hospitalization- related hyperglycemia • Receiving ≤2 U/h insulin infusion with concomitant BG <130 mg/dL • Basal insulin dose ≤48 U/d while receiving insulin drip More likely to experience increasing blood glucose or increased complications on early transition to SC insulin • Underwent complex heart surgeries • At high risk for mediastinitis in ICU • Receiving pressors • Require intra-aortic balloon pump • Receiving corticosteroids • BG >130 mg/dL while receiving insulin infusion • With type 1 diabetes • Basal insulin dose projected to be >48 U/d while receiving insulin drip • Basal insulin infusion rate >2 U/h to maintain BG <130 mg/dL 32 Furnary AP, Braithwaite SS. Am J Cardiol. 2006;98:557-564.
- 33.
- 34. Potential Harm FromInsulin Therapy • The Joint Commission in 2009 considered insulin to be 1 of the 5 highest-risk medicines in the inpatient setting – Consequences of errors with insulin therapy can be catastrophic • In 2008, insulin accounted for 16.2% of harmful medication errors, more than any other product, in an analysis of the USP MEDMARX reporting program data • In 2008-2009, 2685 insulin medication error event reports were submitted to the Pennsylvania Patient Safety Authority 34 Pennsylvania Patient Safety Advisory. Pa Patient Saf Advis. 2010;7:9-17. Available at: http://www.patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2010/Mar7(1)/Pages/09.aspx#bm7.
- 35. Common Features IncreasingRisk of Hypoglycemia in an Inpatient Setting • Advanced age • Decreased oral intake • Chronic renal failure • Liver disease • Beta-blockers 35 ACE/ADA Task Force on Inpatient Diabetes. Endocr Pract. 2006;12:458-468.
- 36. Factors Increasing Riskof Hypoglycemia in an Inpatient Setting • Lack of coordination between dietary and nursing leads to mistiming of insulin dosage with respect to food • Inadequate glucose monitoring • Inadequate insulin dose adjustment • Unsafe work environment • Indecipherable orders 36 Garg R et al. J Hosp Med. 2009;4(6):E5-E7. ACE/ADA Task Force on Inpatient Diabetes. Endocr Pract. 2006;12:458-468.
- 37. Factors Increasing Riskof Medication Errors With Insulin • Use of “sliding scale” insulin in the absence of regularly scheduled insulin • Use of “U” for units being misread as a number • BG testing reporting and transcription errors • Similar names of products, manufacturer’s labeling • Accessibility as floor stock • Nonstandard compounded IV solutions and infusion rates 37 Pennsylvania Patient Safety Advisory. Pa Patient Saf Advis. 2010;7:9-17. Available at: http://www.patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2010/Mar7(1)/Pages/09.aspx#bm7.
- 38. Triggering Events forHypoglycemia • Transportation off ward causing meal delay • New NPO status • Interruption of any of the following: – Intravenous dextrose – TPN – Enteral feedings – Continuous renal replacement therapy 38 ACE Task Force on Inpatient Diabetes and Metabolic Control. Endocr Pract. 2004;10:77-82.
- 39. Summary • Hyperglycemia – Commonin critically patients, both with and without diabetes – Predictor of adverse outcomes, including mortality • Significant improvements in mortality and morbidity with intensive glycemic management have been demonstrated – In some randomized controlled trials – In “before and after” comparisons • Mixed Med-Surg ICU • Good (100-150 mg/dL), but not stringent (80-110 mg/dL) glucose control most reasonable strategy for critically ill patients • IV insulin infusion, using a validated protocol to minimize hypoglycemia, is the preferred approach in critical care setting 39
- 40.