Surviving Sepsis Campaign Guidelines for Management of

Severe Sepsis and Septic ShockDellinger RP, Levy MM, Rhodes A, Annane D, Carcillo JA, Gerlach H, Opal S, Sevransky J,

Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally M, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR,

Rubenfeld G, Webb S, Beale RJ, Vincent JL, Moreno R, and the SSC Management Guidelines

CommitteeCrit Care Med. 2013;41:580–637

Intensive Care Med. 2013;39:165-228

Glucose ControlCrit Care Med. 2013;41:580–637

Intensive Care Med. 2013;39:165-228

Surviving Sepsis Campaign (SSC) 2012 Guidelines

Surviving Sepsis Campaign 2012 Guidelines – Glucose Control

• We recommend protocolized approach to blood glucose management, commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL.

• This protocolized approach should target upper blood glucose <180 mg/dL rather than upper target blood glucose <110 mg/dL. Grade 1ANICE-SUGAR. N Engl J Med. 2009;360:1283–1297 van den Berghe G. N Engl J Med. 2001;345:1359–1367Dellinger P. Crit Care Med. 2013;41:580–637Dellinger P. Intensive Care Med 2013;39:165-228

Surviving Sepsis Campaign 2012 Guidelines – Glucose Control

• Large randomized single-center trial (predominantly cardiac surgical ICU) demonstrated reduced ICU mortality with intensive intravenous insulin targeting blood glucose to 80–110 mg/dL.

van den Berghe G. N Engl J Med. 2001;345:1359–1367

• Second randomized trial of intensive insulin therapy using this protocol enrolled medical ICU patients with anticipated ICU LOS of >3 days; overall mortality was not reduced.

van den Berghe G. N Engl J Med 2006;354:449–461Dellinger P. Crit Care Med 2013; 41:580–637Dellinger P. Intensive Care Med 2013;39:165-228

van den Berghe et al. N Engl J Med. 2001;345:1359

P = 0.005P = 0.01

Intensive Insulin Therapy in Critically Ill Patients

Intensive Insulin Therapy in Critically Ill Patients

van den Berghe et al. N Engl J Med. 2006;354:449

P = 0.40P = 0.02

But…

Surviving Sepsis Campaign 2012Guidelines – Glucose Control

• Subsequent RCTs studied mixed populations of surgical and medical ICU patients and found that intensive insulin therapy did not significantly decrease mortality, whereas the NICE-SUGAR trial demonstrated an increased mortality.Brunkhorst FM. VISEP. N Engl J Med. 2008;358:125–139Preiser JC. Glucontrol. Intensive Care Med. 2009;35:1738Annane D. COIITSS. JAMA .2010;303:341–348NICE-SUGAR. N Engl J Med. 2009;360:1283–1297

Dellinger P. Crit Care Med. 2013;41:580–637Dellinger P. Intensive Care Med. 2013;39:165-228

VISEP Intensive Insulin Trial

Brunkhorst FM. N Engl J Med. 2008;358:125

P=0.36

Preiser JC. Glucontrol. Intensive Care Med .2009;35:1738

0 10 20 30 40 50 60 70 80 90Time, days

100

90

80

70

60

50

40

30

20

10

0

Hos

pita

l sur

viva

l pro

babi

lity

(%)

P = 0.386

Intensive Glucose Control

Control

Intensive vs. Conventional Glucose Control in Critically Ill Patients

Days

Sur

viva

l

0 30 60 90 120 150 180 210 240 270 300 330 360 390

0.0

0.2

0.4

0.6

0.8

1.0

254 147 132 128 121 119 117 7 4 4 4 3 Conventional

255 151 128 124 119 118 118 6 4 2 2 1 1 1 Intensive

Conventional Glucose controlIntensive Insulin Therapy

A

Intensive Insulin Therapy for Septic Shock - COIITSS Study

Annane D. JAMA. 2010;303:341-348

P=0.57

NICE-SUGAR. N Engl J Med. 2009;360:1283

Tight glycemic control=81-108 mg/dL vs. <180 mg/dL

P=0.03

Intensive vs. Conventional Glucose Control in Critically Ill Patients

Surviving Sepsis Campaign 2012 Guidelines - Glucose Control

• As there is no evidence that targets between 140 and 180 mg/dL are different from targets of 110 to 140 mg/dL, the recommendations use an upper target blood glucose ≤180 mg/dL without a lower target other than hypoglycemia.

• Treatment should avoid hyperglycemia (>180 mg/dL), hypoglycemia, and wide swings in glucose levels.Dellinger P. Crit Care Med. 2013;41:580–637Dellinger P. Intensive Care Med. 2013;39:165-228

Tight Glycemic Control in the ICU: Systematic Review and Meta-analysis

Marik PE. Chest. 2010;137:544

02468

101214161820

LEUVEN I

LEUVEN II

VISEP

GLUCONTROL

COIITTS

NICE-S

UGAR

% Intensive insulintherapy

% Control5.1%

0.8%

18.7%

3.1%

17%

4.1%

8.7%

2.7%

16.4%

7.8% 6.8%

0.5%

Severe Hypoglycemia ≤40mg/dL (2.2 mmol/L)

Treatment vs control P<0.001

Surviving Sepsis Campaign 2012 Guidelines - Glucose Control

Mortality in clinical trials of intensive insulin therapy by high or moderate control groups

• We recommend blood glucose values be monitored every 1-2 hours until values and insulin infusion rates are stable, then every 4 hours thereafter. Grade 1C

Dellinger P. Crit Care Med. 2013;41:580–637Dellinger P. Intensive Care Med. 2013;39:165-228

Surviving Sepsis Campaign 2012 Guidelines - Glucose Control

• We recommend that glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may not accurately estimate arterial blood or plasma glucose values. No Grade

Dellinger P. Crit Care Med. 2013;41:580–637Dellinger P. Intensive Care Med. 2013;39:165-228

Surviving Sepsis Campaign 2012 Guidelines - Glucose Control

• Capillary point-of-care testing found to be inaccurate with frequent false glucose elevations over range of glucose levels, but especially in hypoglycemic and hyperglycemic glucose ranges and in hypotensive patients or patients receiving catecholamines..

Hoedemaekers CW. Crit Care Med. 2008;36:3062–3066Khan AI. Arch Pathol Lab Med. 2006;130:1527–1532Desachy A. Mayo Clin Proc. 2008;83:400–405Fekih Hassen M. Diabetes Res Clin Pract. 2010;87:87–91

Dellinger P. Crit Care Med. 2013;41:580–637Dellinger P. Intensive Care Med. 2013;39:165-228

Surviving Sepsis Campaign 2012 Guidelines - Glucose Control