Hyperglycemia in the Hospital

Transcription

1 Time For A Relity Check Getting Awy from Sliding Scle Insulin A system-bsed pproch to improve ptient outcomes in the inptient setting Andrew Ahmnn, MD Hrold Schnitzer Dibetes Helth Center Dibetes nd hyperglycemi re common in the hospitl Hyperglycemi negtively impcts hospitl outcomes Glucose gols re somewht uncertin The key is blnce between control of hyperglycemi nd voiding hypoglycemi Prcticl pproches hve evolved Specil situtions require modifictions Hyperglycemi in the Hospitl Hyperglycemi In The Hospitl Dibetes: Previously dignosed Previously undignosed HbA1c > 6.5% during dmission Hyperglycemi without dibetes dignosis Dibetes dignosed on follow-up Predibetes with overt hyperglycemi during cute physiologic stress Hyperglycemi due to physiologic stress without underlying metbolic bnormlity norml follow-up testing Mortlity = 16% 11% 63% 26% Mortlity = 3.% Mortlity = 1.7% Umpierrez, JCEM 87: , 22 Dibetes New Hyperglycemi Norml Action And Rection Over A Decde Before 21 tlk but no ction Some evidence for concept Detrimentl Physiologic Impct of Hyperglycemi Immune dysfunction Infection dissemintion Metbolic stress response Stress hormones nd peptides Glucose Insulin FFA Ketones Lctte Rective O 2 species Pltelet ggregtion Trnscription fctors IPA ctivity Secondry meditors PAI levels Cellulr injury/poptosis Inflmmtion Tissue dmge Altered tissue/wound repir Acidosis Infrction/ischemi Prolonged hospitl sty Disbility Deth Deedwni P, et l. Circultion. 28;117(12): Modified from Clement S, et l. Dibetes Cre. 24;27(2):

2 Thirty-Dy Mortlity nd In-Hospitl Compliction Rtes re Incresed in Surgicl Ptients with Dibetes Nosocomil Infection Rtes Within The First 14 Postopertive Dys fter Elective Surgery * * * * * Percent 2 Developing Infection > 22 5 Preop POD1 POD2 FrischP, et l. Dibetes Cre. 21;133(8): *p<.1; NS; p<.17 Pomposelli. Erly postopertive glucose control predicts nosocomil infection rte in dibetic ptients. J Prenterl nd Enterl Nutrition; 1998; 22: 77. Hospitl Mortlity Rtes nd Glucose Levels in Non-ICU Ptients Absolute risk of dverse outcome (deth or prolonged sty) incresed 15% per 18-mg/dL increse in glucose levels Mortlity, % Bker EH, et l. Thorx. 26;61(4): N=433 ptients with COPD excerbtions < >163 BG, mg/dl Improved Outcomes with Bsl-Bolus Bolus Insulin in Non-ICU Surgicl Ptients % of Ptients with Complictions 3% 25% 2% 15% 1% 5% % n = 17 p =.3 n = 14 Umpierrez et l Dibetes Cre 211; 34: Complictions include: Wound infection Pneumoni Acute respirtory filure Acute renl filure Bcteremi Portlnd Dibetes Protocol: Insulin Infusion Reduces DSWI (N = 3,554) SCI 4. DSWI (%) CII Ptients with dibetes Ptients without dibetes Action And Rection Over A Decde Before 21 tlk but no ction 21 Vn den Berghe SICU study Prompted ccelerted efforts to improve inptient glucose control Yer DSWI = deep sternl wound infection; CII = continuous insulin infusion. Furnry AP, et l. Ann Thorc Surg. 1999;67:

3 Intensive Insulin Therpy in the Surgicl ICU Improved Survivl Survivl in ICU, % Intensive tretment Conventionl tretment 84 Mortlity 42%, P< Dys After Admission In-Hospitl Survivl, % 1 Vn den Berghe G, et l. N Engl J Med. 21;345(19): Intensive group men = 13 mg/dl Control group men = 153 Intensive tretment Conventionl tretment 84 Mortlity 34%, P< Dys After Admission Glycemic Trgets in Hospitlized Ptients in 25 AACE/ ACE Trgets Intensive cre unit 11 mg/dl Medicl/surgicl floors 11 mg/dl preprndil 18 mg/dl mximl glucose ADA Stndrds of Medicl Cre Dibetes Cre 26; ADA Trgets Criticlly ill As close to 11 mg/dl s possible nd usully under 18 mg/dl Noncriticlly ill Premel glucose 9-13 mg/dl Postprndil glucose < 18 mg/dl Action And Rection Over A Decde Before 21 tlk but no ction 21 Vn den Berghe SICU study Prompted ccelerted efforts to improve inptient glucose control Institutionl system chnges ensued s hospitls ttempted to chieve improved glucose control System Chnges to Improve Glucose Control Multidisciplinry tems/ committees Nursing -- Dibetes Specilist Hospitlists -- Intensivists Anesthesi -- ER Personnel Surgeons -- Phrmcists Qulity Assurnce -- Others Protocol development ICU insulin infusions Optiml subcutneous insulin including specil situtions Trnsitions Forms (orders, flowsheets, krdex) Eduction/ trining for ll involved individuls Monitoring/ glucometrics Glucometrics: : Guiding Success Dt collection: Automtic or mnul Must be vlidted (reviewed) Primry prmeters Efficcy (ccording to gols) Sfety (frequency of hypoglycemi t vrious levels) Multiple options for meningful expression The process is gretly ided by dvncing technology, prticulrly relting to EMRs Schnipper JL et l. J Hosp Med 28; 3:66 Glucometrics - more esily determined by IT systems with EMR - Chnge in ICU Trgets Oregon Helth & Science University

4 EMR Metbolic Record Oregon Helth & Science University Strtegies To Improve Glucose Control Stff eduction to fcilitte chnge in prctices Hospitl protocols to include ll stff providers Pper vs computerized Glycemic consult tem Dibetes eductor driven NP or Phrm D model Endocrinologist model Hospitlists Alone In concert with n endocrinologist nd nurse. Hybrids Hospitlist Bsed Glycemic Tretment Tem Improves Men Full Hospitliztion CBG in Surgicl Ptients Month Men Full Hospitliztion CBG (mg/dl) Bseline -6 to Glycemic Tretment Tem *p<.5, **p<.1 vs. bseline SD to 3 165* ** 22 Oregon Helth & Science University reported by B. Klopfenstein, MD Action And Rection Over A Decde Before 21 tlk but no ction 21 Vn den Berghe SICU study 23 AACE guidelines with ICU gol <11 ADA involved but slightly modified the guidelines 24 ADA Technicl Review published Incomplete studies nd mny questions Met-nlyses nlyses filed to confirm generlized vlue of intensive therpy in the ICU Glucose Control in the ICU/CCU: The Questions End Point Rte BG Trget BG Achieved Tril N Setting Intensive Primry Conventionl Intensive Conventionl Outcome Intensive Conventionl Odds Rtio b RRR b (95% CI) ARR b DIGAMI CCU mg/dl Usul cre 164 mg/dl 18 mg/dl 2-y Group 1, Group 3, _ d _ d NR 25 (AMI) (7.-1. (Group 3) (9.1 (1 mortlity 23.4%; 17.9% Vn den Berghe 26 HI-5 26 (Groups 1 nd 2) 12 MICU 8-11 mg/dl ( CCU (AMI) (GIK) mg/dl (4-1 Glucontrol 111 ICU 8-11 mg/dl 27 ( Ghndi 27 VISEP 28 De L Ros 54 SICU 28 MICU 399 OR 8-11 mg/dl ( f ICU 8-11 mg/dl ( mg/dl ( mg/dl (1-11 Usul cre <288 mg/dl ( mg/dl (7.8-1 <2 mg/dl ( mg/dl ( mg/dl ( mg/dl ( mg/dl ( mg/dl ( mg/dl ( mg/dl ( mg/dl ( mg/dl ( mg/dl (9 144 mg/dl (8 157 mg/dl ( mg/dl ( mg/dl (8.2 Hospitl mortlity 6-mo mortlity ICU mortlity Group 2, 21.2% 37.3% 4.% 2.7% 7.%.94 d ( ) 7.9% 6.1% -1.8% d -3% d NR 16.7% 15.2% -1.5% -1% 1.1 d ( ) Composite e 44% 46% 2% 4.3% 1. d 28-d mortlity 28-d mortlity (.8-1.2) 24.7% 26.% 1.3% 5.%.89 d ( ) 36.6% 32.4% -4.2% d -13% d NR 23 Chrcteristics of These Studies Mny used modifictions of the Leuven protocol extended to multicenter tril High frequency of hypoglycemi 1-2% of ptients hving glucose <4 mg/dl In most cses the trgets were not met Control group trgets were lower Most of the studies stopped erly (underpowered) but didn t show sttisticl differences Rise questions of the consequences of hypoglycemi

5 The Story of Inptient Glucose Control Over the Lst Decde (cont) 29 Nice Sugr study completed Accentuted concerns bout intensive therpy in ICU BG, mg/dl NICE-SUGAR Study: Results Conventionl glucose control Intensive glucose control 8 Bseline Dys After Rndomiztion 354 received IIT gol: mg/dl (time weighted BG = 118 mg/dl) 35 received CIT gol: <18 mg/dl (time-weighted BG = 145 mg/dl) Probbility of Survivl Conventionl glucose control Intensive glucose control Severe hypoglycemi = 6.8% ITT vs.5% in CIT P= Dys After Rndomiztion 9-dy mortlity: IIT, 829 ptients (27.5%); CIT, 751 (24.9%) Absolute mortlity difference: 2.6% (95% CI,.4-4.8) Odds rtio for deth with IIT: 1.14 (95% CI, ; P=.2) Finfer S, et l. N Engl J Med. 29;36(13): The Story of Inptient Glucose Control Over the Lst Decde (cont) 29 Nice Sugr study completed Accentuted concerns bout intensive therpy in ICU -- New Guidelines from AACE / ADA Trget glucose mg/dl AACE/ADA Trget Glucose Level in ICU Ptients Strting threshold of no higher thn 18 mg/dl Once IV insulin is strted, the glucose level should be mintined between 14 nd 18 mg/dl Lower glucose trgets (11-14 mg/dl) my be pproprite in selected ptients Trgets <11 mg/dl or >18 mg/dl re not recommended Not recommended <11 Acceptble Recommended Not recommended >18 28 Moghissi ES, et l; AACE/ADA Inptient Glycemic Control Consensus Pnel. Endocr Prct. 29;15(4). AACE/ADA Trget Glucose Levels in Non ICU Ptients Premel glucose trgets <14 mg/dl Rndom BG <18 mg/dl To void hypoglycemi, ressess insulin regimen if BG levels fll below 1 mg/dl Occsionl ptients my be mintined with glucose rnge below nd/or bove these cut-points Hypoglycemi = BG <7 mg/dl Severe hypoglycemi = BG <4 mg/dl Moghissi ES, et l; AACE/ADA Inptient Glycemic Control Consensus Pnel. Endocr Prct. 29;15(4) The Story of Inptient Glucose Control Over the Lst Decde (cont) 29 Nice Sugr study completed Accentuted concerns bout intensive therpy in ICU -- New Guidelines from AACE / ADA Trget glucose mg/dl New Guidelines from ACP Trget glucose 14-2 mg/dl Prtly the result of Knsgr et l systemtic review Question of wrong messge - - Intensive therpy in ICU ptients defined by gol < 11 mg/dl with present insulin infusions is not dvisble.

6 Possible Resons The Studies Filed to Show Benefit of Tight Glucose Control The generl hypothesis is wrong. Norml glucose levels re bd for some groups The dverse effects of hypoglycemi offsets the benefits of improved men glucose Glucose vribility reduces the benefits of lower men glucose Hyperglycemi-relted Mortlity in the ICU is Relted to Disese Stte Study of 259,4 dmissions to VA ICUs Significnt Assocition: Unstble ngin Acute MI CHF Arrhythmi Respirtory filure GI bleed Pneumoni Sepsis Acute renl filure CVA PE Colectomy Vlve surgery Genitourinry surgery Not sttisticlly ssocited COPD Heptic filure GI neoplsm GI perfortion Peripherl rteril bypss Musculoskeletl problems CABG Amputtion Hip frcture Fcigli M, et l. Crit Cre Med 29; 37:31-39 Hyperglycemi-relted Mortlity in the ICU is Relted to Disese Stte However, J-shped curve -- Wht Are Some Possible Contributory Fctors if Hypoglycemi is the Problem? % Predicted Mortlity Some disese sttes re prone to dverse effects of hypoglycemi POC monitoring ccurcy is indequte to support tight glucose gols Our insulin infusion lgorithms re indequte to rech gols without excess hypoglycemi nd vribility Fcigli M, et l. Crit Cre Med 29; 37:31-39 Are Meters A Problem? POC Meter Interferences Glucose Oxidse Glucose Dehydrogense Whole blood Arteril blood Cpillry blood Anemi Polycythemi Hypoxi Oxygen therpy Hypothermi / Hypotension / Ascorbic Acid / Acetminophen Dopmine Icodextrin Mnnitol Dungn K et l. Dibetes Cre 27 3:43

7 Assessment on POC Glucose in Hospitl POC testing with meters is common in the cute cre setting to direct IV insulin infusions Present ccurcy in this setting could contribute to hypoglycemi with intensive trgets Advnces in glucose meters re likely to help this problem For now, other methods re preferred for tight trgets of < 11 mg/dl Controlling Glucose In The Hospitl Prcticl Aspects Recommendtions for Mnging Inptient Hyperglycemi IV Insulin Criticlly ill ptients in the ICU Antihyperglycemic Therpy Insulin Recommended SC Insulin Non criticlly ill ptients OADs Not Generlly Recommended Clement S, et l. Dibetes Cre. 24;27(2): Moghissi ES, et l; AACE/ADA Inptient Glycemic Control Consensus Pnel. Endocr Prct. 29;15(4) Reltive Proportion of Insulin Requirement (%)* Insulin Requirements in Helth nd Illness Helthy Sick/ Eting Sick/ NPO Clement S, et l. Dibetes Cre. 27: , 24 Illness-Relted Correction Nutritionl Prndil Bsl *Estimtions for illustrtive purposes: requirements my vry widely. Plsm insulin levels Insulin Time-ction profiles Durtion Asprt, Lispro, Glulisine (4 6 hours) Regulr (6 1 hours) NPH (12 2 hours) Detemir (12 24 hours) Glrgine (2-26 hours) hours 24 Hours Strting Insulin In The Hospitl Ptient Previously on Orl Agents Consider 24 hour insulin dose of.5-.6 units/ kg/ dy Lower dose in elderly nd thin Give 5% of this s bsl Glrgine or detemir once dily NPH times dily Give 5% for mels if eting Apportion ccording to reltive mel size Cn give fter the mel if intke uncertin Use supplementl scle nd djust

8 Rndomized Bsl Bolus versus Sliding Scle Regulr Insulin in ptients with type 2 Dibetes Mellitus (RABBIT-2 2 Tril) Sliding Scles: An Addiction We Cn t t Overcome? Sliding Scre insulin doesn t work well. D/C orl ntidibetic drugs on dmission Strting totl dily dose (TDD):.4 U/kg/d x BG between 14-2 mg/dl.5 U/kg/d x BG between 21-4 mg/dl Hlf of TDD s insulin glrgine nd hlf s rpid- cting insulin (lispro, sprt, glulisine) Insulin glrgine - once dily, t the sme time/dy. Rpid-cting cting insulin- three eqully divided doses (AC) Umpierrez GE, et l. Dibetes Cre. 27;3(9): Rbbit 2 Tril: Chnges in Glucose Levels With Bsl-Bolus vs Sliding Scle Insulin BG, mg/dl P< Admit Dys of Therpy Men overll BG difference between the groups during hospitl sty ws 27 mg/dl (P<.1) Umpierrez GE, et l. Dibetes Cre. 27;3(9): Sliding-scle Bsl-bolus BG <14 mg/dl, Ptients, % Rbbit 2 Tril: Tretment Success With Bsl-Bolus vs Sliding Scle Insulin 1% 75% 5% 25% % 66 Bsl-bolus 38 Sliding-scle BG trget of <14 mg/dl ws chieved in 66% using B/B of ptients vs 38% using SSI BG, mg/dl Umpierrez GE, et l. Dibetes Cre. 27;3(9): Sliding-scle Bsl-bolus Admit Dys of Therpy 14% of ptients using SSI remined with BG >24 mg/dl nd were switched to B/B 46 Inptient Dibetes Mngement: Supplementl Insulin Supplementl insulin is OK -- sliding scle is not! My use protocol with vrious levels of expected insulin sensitivity or use outptient rules of sensitivity with llownce for stress If supplementl doses do not reduce the next glucose to < 15 mg/dl, increse the scle ppropritely Supplementl requirements should be reviewed ech 24 hours nd often dded to the next dy s s bseline dose t the pproprite times BG, mg/dl Trnsition From IV to SC Insulin: Risk For Loss Of Glucose Control Lst 12 h IIP P<.1 First 12 h Post IIP IIP, intensive insulin protocol. Czosnowski QA, et l. J Hosp Med. 29;4(1): Totl Insulin Administered, units P<.1 Lst 12 h IIP First 12 Post IIP

9 Trnsition of IV to Subcutneous Insulin Some Dos & Don ts Bsics of SC Insulin After IV Plce ptients needing significnt IV insulin doses on physiologic insulin regimens (mel plus bsl). Don t t use bsl insulin lone in ptients with very poor control on two or more orl gents. Use correction doses for temporry hyperglycemi. Overlp SC nd IV to minimize hyperglycemi escpe relted to short ½ life of IV insulin. Or give 1% bolus of rpid-cting cting nlog t trnsition Use post mel rpid nlogs for uncertin bility to consume food. IV Insulin Overlp of IV / SC Rpid-cting Insulin bsed on intke Bsl glrgine B L D Converting From IV Insulin Infusion to SC In The Hospitl Without Rpid Medicl Improvement Clculte the IV bsl insulin requirement Insulin delivered overnight for 4 hours (stbility) Multiply by 6 = 24 hour bsl requirement Multiply by 8% to get sfe SC dose /24 hours Glrgine or detemir in single doses or NPH in 2+ doses Exmple: Overnight the ptient verged 1.2 u/hr = 4.8 u/ 4 hours 4.8 x 6 = 3 units 3 x.8 = 24 units 24 units glrgine or detemir before brekfst or bedtime or 24 u N in doses Adjust ccording to overnight glucose control Converting From IV Insulin Infusion to SC In The Hospitl With Rpid Medicl Improvement Clculte the IV bsl insulin requirement Insulin delivered overnight for 4 hours (stbility) Multiply by 6 = 24 hour bsl requirement Multiply by 6% 8% to get sfe sfe 24 SC hour dose bsl /24 dose hours Glrgine or detemir in single doses or NPH in 2+ doses Exmple: Overnight the ptient verged 1.2 u/hr = 4.8 u/ 4 hours 4.8 x 6 = 3 units 3 x.8 = 24 units 24 units glrgine or detemir before brekfst or bedtime or 24 u N in doses Adjust ccording to overnight glucose control Typicl Blood Glucose Pttern With Morning Steroid Therpy Typicl Blood Glucose Pttern With Morning Prednisone Therpy Morning glucose is often down to bseline Glucose Level Glucose Level BK Lunch Dinner BK Lunch Dinner

10 Inptient Therpy of Ill Ptients Who Hve Been on Intrvenous Insulin nd AM Steroids Use intrvenous insulin with intrvenous glucose until the ptient cn et Use IV insulin dose of the lst 24 hours to estimte the 24 hour SC insulin requirement B L Dinner HS Regulr/ Anlog 15% 2% 25% NPH 2% 2% Or 4% Glrgine/Detemir Adjust s indicted by CBGs Treting Steroid Induced Hyperglycemi U Colordo NPH Approch Evluted 2 ptients with CF relted DM Given prednisolone in the hospitl On glrgine + RAA insulin Added NPH to the dmission regimen 1 unit per mg of PRED up to 2 mg Add.5 u/ mg from 21-4 mg Add.25 u/mg over 4 mg Compred to incresed bsl-bolus bolus insulin Both groups hd 4% increse in TDI (9 u/d) The group with NPH did better (p <.1) Seggelke S et l. J Hosp Med 211; 6: Specil Nutrition Considertions Nutrition Method Bolus tube feedings Continuous tube feedings Prenterl nutrition Insulin Component Bsl insulin 4% of TDD Nutritionl insulin 6% of TDD s RAA Bsl insulin 4% of TDD Nutritionl insulin s 6% of TDD s divided doses Give insulin IV with nutrition Possible Approch RAA insulin scheduled with ech bolus feeding + RAA insulin correction (lter increse scheduled) + Bsl insulin (glrgine qd or levemir q 12) RAA q 4 hours Regulr q 6 hours or NPH q 8 hours + Bsl insulin Dose find with IV insulin infusion followed by 8% plced in TPN Plus correction insulin. RAA = Rpid Acting Anlog insulin (sprt, glulisine, lispro) Revised from Glycemic Control Resource Room www. Hospitlmedicine.org/ResourceRoomRedesign Fetures Incresing the Risk of Hypoglycemi in n Inptient Setting Advnced ge Renl filure Liver disese Concurrent illness (cerebrl vsculr ccident, congestive hert filure, shock, sepsis) Ventiltor use Concurrent medictions (β-blockers, quinolones, steroids, epinephrine) D Hondt NJ. Dibetes Spectrum. 28;21(4): Events Triggering In-hospitl Hypoglycemi Trnsporttion off wrd, cusing mel dely Filure to mesure blood glucose before insulin doses New NPO sttus Interruption of IV dextrose therpy Totl prenterl nutrition Enterl feedings Continuous venovenous hemodilysis Hrold Schnitzer Dibetes Helth Center Brithwite SS, et l. Endocr Prct. 24;1(suppl 2):89-99.