Clinical Evidence for Glucose Control in the Inpatient Setting

1、1centers for disease control and prevention. diabetes data and trends. available at: /diabetes/statistics/dmany/fig1.htm.212 million bg readings from 653,359 icu patients; mean poc-bg: 167 mg/dl.swanson cm, et al. endocr pract. 2011;17:853-861.34ciah, critical illness associated hyp

2、erglycemia.plummer mp, et al. intensive care med. 2014;40:973-980.49.8225.522.70102030405060ciahrecognized diabetesunrecognized diabetesnormoglycemiapatients (%)prospective observational study(n=1000)n=1826 icu patients.krinsley js. mayo clin proc. 2003;78:1471-1478.05101520253035404580-99100-119120

3、-139140-159160-179180-199200-249250-2993000510152025303540450510152025303540455cabg, coronary artery bypass graft.furnary ap et al. j thorac cardiovasc surg. 2003;125:1007-1021.cardiac-related mortalitynoncardiac-related mortality02468101214162506(reference: mean bg 100-110 mg/dl)kosiborod m, et al.

4、 circulation. 2008:117:1018-1027.7216,775 consecutive first admissions 173 surgical, medical, cardiac icus 73 geographically diverse vamc 9/023/05severity of illnessmean glucosehospital mortalityfalciglia m, et al. crit care med. 2009;37:3001-3009.8falciglia m, et al. crit care med. 2009;37:3001-300

5、9.9falciglia m, et al. crit care med. 2009;37:3001-3009.10* 200 mg/dl.rady my, et al. mayo clin proc. 2005;80:1558-1567.ainla mit, et al. diabet med. 2005;22:1321-1325.*11pasquel fj, et al. diabetes care. 2010;33:739-741.454035302520151050120121-150151-180180blood glucosebg within 24 hours of tpnbg

6、during tpn (days 2-10)12mortality (%)umpierrez ge, et al. j clin endocrinol metab. 2002;87:978-982.in-hospital mortality rate (%)newly discovered hyperglycemiapatients with history of diabetespatients with normoglycemiap .01p .0113n=2471 non-icu patients with community-acquired pneumonia* p=0.03; p=

7、0.01. complications include all in-hospital complications except for abnormalities of glucose.mcalister fa, et al. diabetes care. 2005;28:810-815.mortalitycomplications*141516iqr, interquartile range; tir, time in range; tir-high, time in targeted blood glucose range above median value for cohort; t

8、ir-low, time in targeted blood glucose range below median value for cohort.krinsley js, preiser j-c. crit care. 2015;19:179.8.4716.0915.7614.4405101520no diabetesdiabetestir-hightir-lowp0.0001p=0.5994retrospective study, 2009-2013(n=3297)median tir80.6% (iqr 61.4%-94.0%)median tir55.0% (iqr 35.3%-71

9、.1%)mortality (%)studysettingpopulationclinical outcomefurnary, 1999icudm undergoing open heart surgery65% infectionfurnary, 2003icudm undergoing cabg57% mortalitykrinsley, 2004medical/surgical icu mixed, no cardiac 29% mortalitymalmberg, 1995ccumixed28% mortalityafter 1 yearvan den berghe, 2001*sur

10、gical icumixed, with cabg42% mortalitylazar, 2004or and icucabg and dm60% a fib post op survival 2 yearkitabchi ae, et al. metabolism. 2008;57:116-120.17cii4.03.02.01.00.0dswi (%)8788899091929394959697yearpatients with diabetes patients without diabetes dswi, deep sternal wound infection; cii, conti

11、nuous insulin infusion.furnary ap, et al. ann thorac surg. 1999;67:352-362.181086408788899091929394989900patients with diabetes patients without diabetes295969701iv insulin protocolfurnary ap, et al. j thorac cardiovasc surg. 2003;125:1007-1021.19krinsley js. mayo clin proc. 2004;79:992-1000. 20van

12、den berghe g, et al. n engl j med. 2001;345:1359-1367.21van den berghe g, et al. n engl j med. 2001;345:1359-1367.p0.04p=0.007p=0.003p0.001p=0.003p=0.0122trial n setting primary outcome odds ratio(95% ci)p valuevan den berghe20061200micu hospital mortality 0.94 (0.84-1.06) n.s.hi-52006240ccu ami6-mo

13、 mortality nr n.s.glucontrol2007 1101icu icu mortality 1.10(0.84-1.44) n.s.visep2008 537 icu 28-d mortality 0.89(0.58-1.38) n.s.de la rosa 2008 504sicumicu 28-d mortality nr n.s.nice-sugar20096104icu 3-mo mortality 1.14(1.02-1.28) 0.05rabbit 2 surgery2011211sicucomposite of postop outcomes3.39(1.50-

14、7.65)0.00323van den berghe g, et al. n engl j med. 2006;354:449-461.24patients (%)conventional treatmentintensive treatmentintention to treat26.824.24037.3icu mortalityhospital mortalityhazard ratio 0.94 (95% ci 0.84-1.06)p=0.31p=0.33icu los 3 days38.131.352.543.0icu mortalityhospital mortalityp=0.0

15、5p=0.009mortalityreduction17.9%mortalityreduction18.1%van den berghe g, et al. n engl j med. 2006;354:449-461.patients (%)25van den berghe g, et al. n engl j med. 2006;354:449-461.26preiser jc, et al. intensive care med. 2009;35:1738-1748.27intensive insulin therapy(n=536)conventional insulin therap

16、y(n=546)pnondiabetic patients 872 patients deaths 44617.0%42616.2%0.738diabetic patients 210 patients deaths9016.7%12011.7%0.298preiser jc, et al. intensive care med. 2009;35:1738-1748.28* blood glucose 40 mg/dl.preiser jc, et al. intensive care med. 2009;35:1738-1748.intensive insulin therapy(n=536

17、)conventional insulin therapy(n=546)pmortality rate, %16.9715.200.465patients with hypoglycemia,* %001death among patients with hypoglycemia,* %32.653.80.162129brunkhorst fm, et al. n engl j med. 2008:358:125-139.30blood glucoseoverall survivalno difference in mortalitydaysconventional ther

18、apyintensive therapy0123456789mean blood glucose (mg/dl)10 11 12 13 140501001502000102030405060708090100daysprobability of survival (%)conventional therapy (n=290)intensive therapy (n=247)0102030405060708090100data from 537 patients:247 received iit goal: 80-110 mg/dl: mean bg 112 mg/dl290 received

19、cit goal: 180-200 mg/dl: mean bg 151 mg/dliit, intensive insulin therapy; cit, conventional insulin therapy.brunkhorst fm, et al. n engl j med. 2008:358:125-139.31intensive insulin therapy(n=247)conventional insulin therapy(n=290)pmortality rate, % 28 days 90 days24.739.726.035.40.740.31patients wit

20、h hypoglycemia,* %17.0%4.1%0.001sofa score (mean) 95% ci7.87.3--8.20.16* blood glucose 40 mg/dl.brunkhorst fm, et al. n engl j med. 2008:358:125-139.32 conventional insulin therapy(n=290)intensive insulin therapy(n=247)(glucose 40 mg/dl)# of patients with hypo events1242% of patients with h

21、ypo events4.117.0% of patients with life-threatening hypo events2.15.3hypoglycemia identified as an independent risk factor for mortality* personal communication, dr. frank brunkhorstbrunkhorst fm, et al. n engl j med. 2008:358:125-139.33intensive(n=254)standard (n=250)mean am glucose, mg/dl11714828

22、-day mortality, n (%)93 (36.6)81 (32.4)in-hospital mortality, n (%)102 (40)96 (38.4)severe hypoglycemia(40 mg/dl), n (%)21 (8.3)2 (0.8)de la rosa gdel c, et al. crit care. 2008;12:r120.504 patients; 1/2 medical; single-center study from colombia34finfer s, et al. n engl j med. 2009;360:1283-1297.35*

23、 no significant numbers of ct surgery patients. no significant numbers of ccu patients.finfer s, et al. n engl j med. 2009;360:1283-1297.36bars are 95% confidence intervals. dashed line =108 mg/dl (upper limit of intensive glucose control target range).finfer s, et al. n engl j med. 2009;360:1283-12

24、97.37density plot for mean time-weighted blood glucose levels for individual patientsthe dashed lines indicate the modes (most frequent values) in the intensive control group (blue) and the conventional-control group (red), as well as the upper threshold for severe hypoglycemia (black).finfer s, et

25、al. n engl j med. 2009;360:1283-1297.38outcome measure intensive groupconventional groupmorning bg (mg/dl)118 + 25145 + 26hypoglycemia(40mg/dl)206/3016 (6.8%)15/3014(0.5%)28-day mortality (p=0.17)22.3%20.8%90-day mortality (p=0.02)27.5%24.9%finfer s, et al. n engl j med. 2009;360:1283-1297.39kaplanm

26、eier estimates for the probability of survival% hr = 1.11 95 confidence interval:(1.01-1.23)finfer s, et al. n engl j med. 2009;360:1283-1297.40finfer s, et al. n engl j med. 2009;360:1283-1297.41finfer s, et al. n engl j med. 2009;360:1283-1297.42finfer s, et al. n engl j med. 2009;360:1283-1297.43

27、finfer s, et al. n engl j med. 2009;360:1283-1297.44tight glycemic control in critically ill adults a meta-analysis of 29 randomized controlled trialsvery tight, moderately tight glycemia control and severe hypoglycemia wiener rs, et al. jama. 2008:300:933-944.45tight glycemic control in critically

28、ill adults a meta-analysis of 29 randomized controlled trialssicu, micu, mixed icu, and severe hypoglycemiawiener rs, et al. jama. 2008:300:933-944.46griesdale de, et al. cmaj. 2009;180:821-827.47tight glycemic control in critically ill adults a meta-analysis of 26 randomized controlled trials(13,56

29、7 patients)all-causemortalitymixed icugriesdale de, et al. cmaj. 2009;180:821-827.48tight glycemic control in critically ill adults a meta-analysis of 26 randomized controlled trials(13,567 patients)severe hypoglycemia(40 mg/dl)griesdale de, et al. cmaj. 2009;180:821-827.49umpierrez ge, et al. diabe

30、tes care. 2007;30:2181-2186.days of therapybg (mg/dl)100120140160180200220240admit1sliding scalebasal bolus*2345678910* p0.05.sliding scale regular insulin (ssri): given 4 times daily. basal-bolus regimen: glargine once daily; glulisine before meals.0.4 u/kg/d x bg between 140-200 mg/dl0.5 u/kg/d x

31、bg between 201-400 mg/dl*50* p0.001.umpierrez ge, et al. diabetes care. 2011;34: 256-261.51p=0.003p=nsp=0.05p=0.10p=0.24* wound infection, pneumonia, respiratory failure, acute renal failure, and bacteremia.umpierrez ge, et al. diabetes care. 2011;34: 256-261.5253bg, blood glucose; cabg, coronary ar

32、tery bypass surgery.umpierrez g, et al. diabetes care. 2015;38:1665-1672.4249345248550102030405060all patientsdiabetesno diabetesintensive (bg 100-140 mg/dl)conservative (bg 141-180 mg/dl)patients (%)randomized, controlled trial(n=302)p=0.08p=0.87p=0.008prevalence of complications54nice-sugar, normo

33、glycemia in intensive care evaluation and survival using glucose algorithm regulation.niven dj, et al. jama intern med. 2015;175:801-809.time series analysis, 2001-2012(n=113 icus, 353,464 patients)01020304050start of studyimmediately afterbefore nice-immediately afterend of studytight glycemic cont

34、rol (bg 80-110 mg/dl)hypoglycemia (bg 180 mg/dl)patients (%)555657swanson cm, et al. endocr pract. 2011;17:853-861.no. patients:3,484,795no. poc-bg:49,191,313icu:12,176,299non-icu:37,015,01458conditionsevere hypoglycemiamortalitydiabetes3.07*0.97septic shock2.03*1.33creatinine 3 mg/dl1.101.30*mechan

35、ical ventilation2.11*2.43*tight glycemia control1.59*0.67*apache ii score1.07*1.14*age1.011.03*severe hypoglycemia(40 mg/dl)2.28*krinsley js, grover a. crit care med. 2007;35:2262-2267.59severe hypoglycemia (40 mg/dl) is associated with an increased risk of mortality (or, 2.28; 95% ci, 1.41-3.70; p=

36、.0008)hypoglycemia was a predictor of higher mortality in patients not treated with insulin, but not in patients treated with insulin60nice-sugar study investigators. n engl j med. 2012;367:1108-1118.risk of death with severe hypoglycemia vs no hypoglycemia 1.7-fold in patients receiving insulin 3.8

37、-fold in patients not receiving insulin61lowest blood glucose recorded during hospital stay3.0 mmol/l or 55 mg/dln+44; 20 deaths3.1-6.5 mmol/l or 56-119 mg/dln=364; 101 deaths6.6 mmol/l or 120 mg/dln=276; 107 deaths1.93(1.18-3.17)-3.5-2.5-1.5-2.53.5referent1.48(1.09-1.99)svensson am, et al.

38、 eur heart j. 2005 26:1255-1261.62kosiborod m, et al. jama. 2009;301:1556-1564.unadjusted results hypoglycemiano hypoglycemiap valueall patientsn=482n=7338 in-hospital mortality61 (12.7%)701 (9.6%)0.026no insulin treatmentn=136n=4639 in-hospital mortality25 (18.4%)425 (9.2%)0.0003insulin-treated pat

39、ientsn=346n=2699 in-hospital mortality36 (10.4%)276 (10.2%)0.9263kosiborod m, et al. jama. 2009;301:1556-1564.64no. events/total no. patientshypoglycemic eventsstudyiitcontrolrisk ratio (95% ci)favors iitfavors controlvan den berghe et al39/7656/7836.65 (2.83-15.62)henderson et al7/321/357.66 (1.00-

40、58.86)bland et al1/51/51.00 (0.08-11.93)van den berghe et al111/59519/6055.94 (3.70-9.54)mitchell et al5/350/3511.00 (0.63-191.69)azevedo et al27/1686/1694.53 (1.92-10.68)de la rosa et al21/2542/25010.33 (2.45-43.61)devos et al54/55015/5513.61(2.06-6.31)oksanen et al7/391/519.15 (1.17-71.35)brunkhor

41、st et al42/24712/2904.11(2.2-7.63)iapichino et al8/453/452.67 (0.76-9.41)arabi et al76/2668/2579.18 (4.52-18.63)mackenzie et al50/1219/1195.46 (2.82-10.60)nice-sugar206/301615/301413.72 (8.15-23.12)overall654/613898/62095.99 (4.47-8.03)griesdale de, et al. cmaj. 2009;180:821-827.0.1110risk ratio (95% ci)65wright rj, frier bm. diabetes metab res rev. 2008;24:353-363.6667kavanagh bp, mccowen kc. n engl j med. 2010;363:2540-2546.yearorganizationpatien