Surviving Sepsis Campaign

Guidelines for Management of

Severe Sepsis and Septic Shock

Dellinger 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
Committee
Crit Care Med. 2013;41:580637
Intensive Care Med. 2013;39:165-228

Surviving Sepsis Campaign (SSC)

2012 Guidelines

Glucose Control
Crit Care Med. 2013;41:580637
Intensive Care Med. 2013;39:165-228

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 1A
NICE-SUGAR. N Engl J Med. 2009;360:12831297
van den Berghe G. N Engl J Med. 2001;345:13591367
Dellinger P. Crit Care Med. 2013;41:580637
Dellinger 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 80110 mg/dL.
van den Berghe G. N Engl J Med. 2001;345:13591367

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;354:449461
Dellinger P. Crit Care Med 2013; 41:580637
Dellinger P. Intensive Care Med 2013;39:165-228

Intensive Insulin Therapy in

Critically Ill Patients

P = 0.005

P = 0.01

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

Intensive Insulin Therapy in

Critically Ill Patients

P = 0.40
P = 0.02

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

But

Surviving Sepsis Campaign 2012

Guidelines 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;358:125139
Preiser JC. Glucontrol. Intensive Care Med. 2009;35:1738
Annane D. COIITSS. JAMA .2010;303:341348
NICE-SUGAR. N Engl J Med. 2009;360:12831297
Dellinger P. Crit Care Med. 2013;41:580637
Dellinger P. Intensive Care Med. 2013;39:165-228

VISEP Intensive Insulin Trial

P=0.36

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

Intensive vs. Conventional Glucose

Control in Critically Ill Patients
Hospital survival probability (%)

100
90
80

Intensive Glucose Control

70
60

Control

50
40

P = 0.386

30
20
10
0
0

10

20

30

40

50

60

70

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

80

90

Intensive Insulin Therapy for

Septic Shock - COIITSS Study

0 .6
0 .4

Conventional Glucose control

Intensive Insulin Therapy

P=0.57

0 .2
0 .0

S u rv iv a l

0 .8

1 .0

254

147

132

128

121

119

117

255

151

128

124

119

118

118

30

60

90

120

150

180

210

240

270

300

330

Days

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

Conventional
1

360

390

Intensive

Intensive vs. Conventional Glucose

Control in Critically Ill Patients

P=0.03

Tight glycemic control=

81-108 mg/dL vs. <180 mg/dL

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

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;41:580637
Dellinger 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

Severe Hypoglycemia
40mg/dL (2.2 mmol/L)
18.7%

17%

16.4%

8.7%
5.1%
3.1%
0.8%

4.1%

7.8%

6.8%

2.7%
0.5%

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

Surviving Sepsis Campaign 2012

Guidelines - Glucose Control
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;41:580637
Dellinger 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;41:580637
Dellinger 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;36:30623066
Khan AI. Arch Pathol Lab Med. 2006;130:15271532
Desachy A. Mayo Clin Proc. 2008;83:400405
Fekih Hassen M. Diabetes Res Clin Pract. 2010;87:8791
Dellinger P. Crit Care Med. 2013;41:580637
Dellinger P. Intensive Care Med. 2013;39:165-228