Presentation on theme: "Insulin : In-patient use"— Presentation transcript:
1 Insulin : In-patient use Novo Nordisk India, Bangalore
2 Insulin : In-patient use Section 1: BackgroundSection 2: Advantages, indications, componentsSection 3: Insulin IV infusion protocolsSection 4: Practical considerationsSection 5: ConclusionI’ll be presenting the topic under these 5 sections
4 Insulin : in-patient use – current status Adults with diabetes6 times more likely to be hospitalized than those without diabetesHospitalized diabetic patientsoften have poor glycemic controlincreased susceptibility to complicationslengthening their hospital stays.We all acceptimportance of tight glucose control in outpatient settingsWe do not appreciateits importance in hospitalized patientsThis slide discusses the current status of mangement of hospitalized diabetic patients
5 Reasons and consequence Reason for admissionnot diabetesInfection, fever, surgery, intensive careConsequenceDiabetes treatment becomes secondaryThe above reasons impair insulin actionSteroid therapy commonly used in ICU and wards also impair insulin actionHere we discuss the reasons and consequence of the current status discussed in the previous slide
6 Clinicians’ perceptions about hyperglycemia in in-patients Hyperglycemia is beneficialbrain & injured tissues require glucosethey don’t require insulin for glucose uptakeTreat hyperglycemia only if BG>215 mg/dlBG<200 mg/dl is acceptableWe do not want hypoglycemia as a complicationMore than the reasons recounted in the previous slide, these perceptions are probably responsible for the current status
7 Insulin: in-patient use - Summary Hospital diabetes is suboptimally managedThere is a case forpromoting a more aggressive approachdeveloping a framework for attaining glycemic control in diabetic inpatientsThese summarize the current status and build our case for the current topic
8 Insulin : In-patient use Section 2: Advantages, indications and componentsLet us begin by looking at the advantages, indications and components of insulin therapy for in-patients
9 Why insulin and not OADs in hospitalized diabetics? (1) OADs disadvantages in hospitalSulfonylureasLong-acting , hypoglycemiaMetforminRenal impairment common in ICU/ward patientsAcarboseEffective only with foodGlitazonesNot preferred in hospitalized cardiac patientsThis slide recounts the obvious reasons for not considering oral antidiabetic drugs for hospitalized diabetics
10 Why insulin and not OADs in hospitalized diabetics? (2) Insulin - advantages in hospitalShort-actingEasy switch-on & offSubstantial benefits irrespective of reason for admissionInexpensive therapyReduces in-hospital stayReduces ICU complicationsneed for mechanical ventilation, blood transfusionAcute renal failure, polyneuropathy (muscle wasting)These are the advantages of insulin for hospitalized diabetics
11 Indications for insulin in hospital Diabetic ketoacidosis / HONKOthersPoorly controlled diabetes despite regular treatment with/without insulin (BG>350 mg/dl)Type 1 diabetes patients who are fasting or perioperativeHyperglycemic postoperative ICU patientsDiabetic patients with myocardial infarctionThese are the standard indications for insulin use in hospital
12 Components of insulin therapy in hospital RehydrationPatients are given IV fluids (e.g. saline infusion)Intravenous infusion of insulin (Actrapid®)Each unit will have a protocolElectrolyte correctionIrrespective of Serum K levels, DKA patients require KAll IV insulin therapy promotes K uptake along with glucose by body cells.Any K-loss makes heart susceptible to arrhythmiasMost IV insulin thearpy will have added KGIK (Glucose-Insulin-Potassium) infusionAttention to cardiac and renal functionThis in a nutshell are the components of insulin therapy in hospital.
13 Insulin : In-patient use Section 3: Insulin IV infusion protocolsIn this section, we will explore the various Insulin IV infusion protocols
14 Sliding scales and earlier practices Recommendations HistorySliding scales and earlier practicesRecommendationsSince Insulin IV infusion are yet a evolving subject, the last word is still to be written, I’ll discuss the topic under these heads.
16 History of acute dosing Fixed dosing regimensSubcutaneous injectionsSubcutaneous infusionsIntravenous infusions‘Sliding scale’ regimensIntravenous infusion ‘algorithms’Eg. Post CABG, post-MI, critically-illThis is how IV insulin infusion has evolved. from fixed dosage regimens to sliding scales to the various protocols published as clinical trial reports in standard literature.
17 Sliding scales and earlier practices We’ll now look at sliding scales, earlier practices based on sliding scales and their shortcomings
18 Sliding Scale Insulin (1) Subcutaneous ‘conventional’ exampleMonitor [BG] q 4-6 h[BG] (mg/dL) Regular SC insulin< amp D50W, specialist consultn70 – No insulin201 – U251 – U301 – U351 – U> U, specialist consultnArch Intern Med 1997;157:This is the classical sliding scale we all know and may have practised or still practising
19 Sliding Scale Insulin (2) ShortcomingsQueale et al, 1997, prospective cohort studyInpatients receiving ‘sliding scale’ subcutaneous regimens23 % experienced hypoglycemia (≤ 60 mg/dL)40 % experienced hyperglycemia (≥ 300 mg/dL)Patients receiving ‘sliding scale’ alone had 3x higher risk of hyperglycemia than those on standing regimenArch Intern Med 1997;157:Literature comes down quite heavily on sliding scales as presented here and the next two slides
20 Sliding Scale Insulin (3) Shortcomings (contd.)Non-physiologic strategy with a retrospective reaction to BGArbitrary thresholds of goal BG require hyperglycemia before any interventionFails to incorporate basal requirements and cannot predict dosage requirementsPromotes glucose ‘roller coaster’Failure to re-evaluate promotes poor titration and reinforces ‘ignorance is bliss’Patients rate control as only ‘fair’see previous slide
21 Sliding Scale Insulin (3) Shortcomings (contd.)Does anyone here know how to make insulin work backwards?”“…invented by a ‘take it easy’ mind.”“…sliding scale orders do not serve anypurpose other than sugar-coating the physician’s clinical deficiencies.”“Action without benefit.”Arch Intern Med 1997;157:489Practical Diabetol 1990;9:1-4Arch Intern Med 1998;158:1472see previous slide
22 Sliding Scale Insulin (3) Call to action against the lip service paid to inpatient diabetes careCall for the banning of the insulin sliding scale use as the sole diabetes orderJ Gen Intern Med May;19(5 Pt 1):
23 Sliding Scale Insulin (4) IV infusion exampleStart infusion at 1.0 U/hrMonitor [BG] q 2 h[BG] (mg/dL) Regular IV insulin< 70 D/C infusion, give glucose71 – 110 ↓ rate by 0.6 U/hr111 – 150 ↓ rate by 0.3 U/hr151 – No change201 – ↑ rate by 0.3 U/hr251 – ↑ rate by 0.6 U/hr> Bolus 8 units IV, ↑ by 1.0 U/hrHow about a sliding scale infusion
24 Sliding Scale Insulin (4) Early IV infusion algorithms - impactHyperglycemic CrisesIV infusion algorithm reduced the risk of hypoglycemia vs. conventional therapy 5 % vs. 23 % (p < 0.01)Post-surgical patientsIV infusion algorithm reduced BG to between mg/dL within 8 hoursArch Intern Med 1997;157:669-75;Diabetes Care 1987;10:722-8The impact of these early infusion algorithms indeed was better
25 Sliding Scale Insulin (4) IV infusion vs. Subcutaneous dosingHyperglycemic CrisesIV infusion had faster decline in BG and ketones within first 2 hoursLower incidence of hypoglycemia and hypokalemiaSimpler and more convenientPost-surgical patientsIV infusion had better control of BG during surgery and post-op days 1-3Proportion of patients with target BG twice as highN Engl J Med 1977;297:238-41J Pediatr 1977;91:701-5Anaesthesia 1988;43:533-7.And the betterment came about in these ways
26 RecommendationsHaving looked at the history and sliding scales, let us now look at some standard IV infusion protocols which could be the “recommendations” going by the current level of evidence-based approach to the topic
27 Recommended infusion algorithms For diabetics undergoing surgeryEuropean Diabetes Policy Group, 1991Clinical Outcome StudiesPost-CABG‘Portland’ Protocol (150 – 200 mg/dL)Post-MI‘DIGAMI’ Protocol (126 – 196 mg/dL)Critically-ill‘Leuven’ Protocol (80 – 110 mg/dL)These are the ones which could be recommended.Let us look at each one individually.
28 Diabetics undergoing surgery - EDPG, 1991 recommendation (1) General instructionsSurgeries and procedures should be scheduled for the early morning,when they will have the least effect on the patient’s treatment program.Blood glucose levels should be monitored q1h/q2hbefore, during, and after surgery or procedure.Sliding scalediscouragedgreater likelihood of wider fluctuations in blood glucose levels, especially in type 1 diabetic patientsThis and the next 2 slides contain recommendation on IV insulin infusion for diabetics posted for surgey.These are generally applicable.
29 Diabetics undergoing surgery - EDPG, 1991 recommendation (2) Type 1 diabetesPlace on an insulin drip (maintenance rate, 1 to 2 U/h) with a 5% dextrose solution at 75 to 125 cc/h, adjusted to maintain blood glucose levels between 100 and 150 mg/dL.Alternatively, give 1/2 to 2/3rd of the usual dose of long-/intermediate-acting insulin on the morning of procedure.Type 2 diabetes, taking an oral hypoglycemic agentHold the medication on the day of procedure and resume when tolerating a normal diet.Metformin must be held for safety concerns (i.e., possible perioperative alteration in renal function) - resumed 48 h postoperatively after normal renal function is securedAlpha-glucosidase inhibitors - because these drugs are effective only when taken with mealsIf pills are allowed, thiazolidinediones can be continued, although, due to their prolonged action, missing a dose or two should not affect glycemic control.Type 2 diabetes, treated with insulinGive one half of long-/intermediate-acting insulin on the morning of procedure.And these are specific to type 1 and type 2 diabetics prior to surgery.
30 Diabetics undergoing surgery - EDPG, 1991 recommendation (3) Use 500 ml 10 % ( 100 g/l ) glucose ( dextrose ) containing :Human Actrapid 16 Upotassium chloride 10 mmolInfuse at 80 ml/hConsider higher dose ( 20 U ) if obese, or initial blood glucose highConsider lower dose ( 12 U ) if very thin, or usual insulin dose lowDecrease dose by 4 U if glucose falling and normal or lowIncrease dose by 4 U if glucose rising or highContinue the GIK infusion until min after first mealUse higher strength glucose solutions if water volume a problemCheck for dilutional hyponatraemia dailyThis is Prof Alberti’s protocol followed by most and recommended by the European diabetes policy group
31 Post-CABG - ‘Portland’ Protocol (1) Initiation ‘Goal’ 150 – 200 mg/dLBG (mg/dL) Insulin (units/hr)<150 –201 –>MonitoringQ 1 h until BG mg/dL with < 15 mg/dL changeand infusion rate unchanged x 4 hours, then q 2 hQ 30 min when weaning vasopressors (epi)May stop q 2 h testing on post op day 3Ann Thorac Surg 1999;67:This is the famous Portland protocol for post-CABG patients.This is how IV insulin was initiated.
32 Post-CABG - ‘Portland’ Protocol (2) TitrationThese were the titration steps
33 Post-MI - DIGAMI protocol (1) Reasons why cardiologists have not taken up glucose -insulin infusionSupply of Glucose means ATP is required for its cellular uptake. This means ATP required for myocardium may be diverted elsewhereIncreased glucose means increased lactic acid accumulation in myocardial cellsPrior trialsLarge number, small sample size, low doses of GIK, conflicting reports and inconclusiveNo pharmaceutical sponsors for GIKNow we come to the famous DIGAMI protocol from the Swedish group of Malmberg et al.But first, let us look at reasons why cardiologists have still not taken up GIK infusions
34 Post-MI - DIGAMI protocol (2) “Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction” studySwedish study of 1990sParticipantsacute MI and diabetes (FPG > 198 mg/dl)randomly assigned to either to IV insulin and glucose for at least 24hfollowed bydaily insulin injections 4 times-a-day for the next 3 months orconventional therapyHowever DIGAMI changed all that.What was DIGAMI?
35 Post-MI - DIGAMI protocol (3) Study question: whether mortality was decreased by tight control both initially and if continued over time.The results showed that insulin-glucose infusion followed by intensive subcutaneous insulin in patients with acute MI and diabetes improves long-term survival.The mortality reduction was 30% in the treatment group vs controlsThis reduced mortality was maintained at a mean follow-up of 3.4 yearsThese were the study questions and the answer
36 Post-MI - DIGAMI protocol (3) Prepare infusion mixture as follows:Add 80 iu soluble insulin to 500 ml 5 % glucoseInfuse initially at 30 ml per hourMeasure blood glucose every 1-2 hTitration steps> 15 mmol/L Give 8 iu soluble insulin as iv bolusincrease infusion rate by 6 ml/h> Increase infusion rate by 6 ml/h> Maintain current rate> Decrease infusion rate by 6 ml/h< 4 Stop infusion until glucose > 7 mmol/lGive ml glucose iv if symptomatichypoglycemiaRestart infusion with rate decreased by 6 ml/hWhat was the protocol itself?These were the titration stepsJ Am Coll Cardiol 1995;26:57-65
37 Post-MI - DIGAMI protocol (3) Maintenance and follow-upContinue the insulin infusion till stable normoglycemia and maintained for > 24 hourLater, start subcutaneous insulin administrationRegimenHuman Actrapid three times a day before mealsHuman Insulatard (NPH) in the evening (to provide overnight basal insulin requirement)Adjust dose by periodic blood glucose estimations.These were the maintenance and follow-up recommendationsJ Am Coll Cardiol 1995;26:57-65
38 Critically ill - Leuven protocol (1) Study challenged all existing perceptions about hyperglycemia as mythsHypothesis: All ICU cases require insulinAggressively lower BG < 110 mg/dlBenefits of intensive insulin so good that study was stopped midway and all patients given intensive insulinMortality reduction 40%Finally, we look at the Leuven protocol.This is a famous paperPublished in New England Journal of Medicine Nov 2001, the study challenged all doctors’ perceptions about hyperglycemia as myths.Leuven is a place in Belgium and some of you might have heard the main author Greet van den Berghe, a lady doctor and a intensive care specialist who has visited India and spoken about her study at a past NNDU.Leuven study was sponsored by Novo Nordisk.
39 Critically ill - Leuven protocol (2) Initiation ‘Goal’ 80 – 110 mg/dLBG (mg/dL) Insulin (units/hr)>>Initial titration[BG] (mg/dL) Insulin (units/hr)No change110 – ↑ by 1 unit/hr> ↑ by 2 unit/hrMonitor [BG] q 1-2 h initially, q 4 h once patient stableN Engl J Med 2002;346:1586-8, Supplementary Appendix 1This is the protocol.
40 Critically ill - Leuven protocol (3) If [BG] ↓ by > 50% after dosage adjustment, ↓ infusion rate, monitor [BG] more frequentlyMaximal arbitrary dose is 50 units/hrAt ICU discharge, d/c protocol, adopt BG goal of 200 mg/dLThe protocol appeared exclusively as a special supplement as there was a great demand from the readers of the main study paper in the journal.N Engl J Med 2002;346:1586-8, Supplementary Appendix 1
41 Guidelines (1): ACE American College of Endocrinology Hyperglycaemia is commonTight metabolic control is importantUpper limit for glycemic targets in ICU: 110 mg/dlInsulin- currently the only available agent for effectively controlling glycemia in hospitalProtocols for CII therapy have been shown to be safe & effective in achieving glucose targetsSurgical pts. discharged from ICU to lower –acuity units- glucose levels should be maintained as close as possible to normal either by intensive SQ therapy or preferably by continuation of IV insulin therapy if possibleACE position statement on in patient diabetes & metabolic control, Endocr Pract. 2004;10(1):77-82
42 Guidelines (2): ADAThe only method of insulin delivery specifically developed for use in the hospital is continuous intravenous infusion, using regular crystalline insulinIV route for insulin administration surpasses s.c. route w.r.t.rapidity of onset of effect in controlling hyperglycemiaoverall ability to achieve glycemic controlmost importantly, nonglycemic patient outcomesDuring IV insulin infusion used to control hyperglycemic crises, hypoglycemia (if it occurs) is short-lived, whereas in the same clinical settings repeated administration of subcutaneous insulin may result in “stacking” of the insulin’s effect, causing protracted hypoglycemiaClement S et al. Diabetes Care Feb 2004; 27(2):553-91
43 Insulin : In-patient use Section 4: Practical considerationsLet us look at some practical aspects of implementing these protocols in our hospitals
44 Practical considerations (1) Desirable IV insulin (Actrapid®) infusion protocolsDiabetic KetoacidosisFor diabetics undergoing surgeryFor diabetics who have a AMIFor all ICU patientsAll institutions must develop these IV insulin infusion protocols that are desirable in all our hospitals
45 Practical considerations (2) We need to overcome theseLimitations of literatureNot applicable to many populationsSafety concerns over widespread applicationLack of simple, easy to use algorithmsThe implementation will improve with theseConsider enrolment in clinical trialsMultidisciplinary approachMonitoring is paramountWe need to overcome a few of these and then improve implementation
46 Practical considerations (3) Monitoring - HyperglycemiaVitals:Temp, BP, HR, RRPhysical examination:Fatigue, drowsiness, obtundation, comaBlurred vision, dry eyes/mouth/mucus membranesWeak, rapid pulseDeep, labored breathing, acetone breathPolyphagia, polydipsia, polyuriaFlushed, dry skinLabs:BG, ketones, electrolytes, BUN, Cr, urine electrolytes, osmolarity and urinalysis prnThese are a few tips to monitoring hyperglycemia
49 Conclusions (1)We all accept importance of tight glucose control in outpatient settingsWe must appreciate its importance in hospitalized patients‘Sliding scale’ subcutaneous insulin is suboptimalIntravenous dosing with early algorithmssafer and more effective than subcutaneous dosingInsulin infusion algorithms used in clinical trialseffectively control BG and improve outcomes in acutely-ill patient subgroupsLet me conclude with these statements
50 Conclusions (2) Let us focus on better practices………… Routine ward casesany diabetic admitted in a ward for reasons other than diabetesDiabetics who undergo surgeryAny surgeryDiabetics who have AMIalong with routine thrombolysisIntensive care unitsAll cases (even non-diabetics) because of stress hyperglycemia
51 Conclusions (3) Irl B. Hirsch “Indeed, inpatient diabetes management has developed into an area of medicine that is less evidence-based and more of an ignorance-based culture with a core component of sliding scale insulin, a relic from generations past with no proven efficacy”J Clin Endocrinol Metab 2002;87:976.And a quoteworthy quote