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;41:580–637
Intensive Care Med. 2013;39:165-228
Surviving Sepsis Campaign (SSC)
2012 Guidelines
Glucose Control
Crit Care Med. 2013;41:580–637
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;360:1283–1297
van den Berghe G. N Engl J Med. 2001;345:1359–1367
Dellinger P. Crit Care Med. 2013;41:580–637
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 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;354:449–461
Dellinger P. Crit Care Med 2013; 41:580–637
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;358:125–139
Preiser JC. Glucontrol. Intensive Care Med. 2009;35:1738
Annane D. COIITSS. JAMA .2010;303:341–348
NICE-SUGAR. N Engl J Med. 2009;360:1283–1297
Dellinger P. Crit Care Med. 2013;41:580–637
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
0.4
Survival
0.6
0.8
1.0
A
Conventional Glucose control
Intensive Insulin Therapy
0.0
0.2
P=0.57
254
147
132
128
121
119
117
7
4
4
4
3
255
151
128
124
119
118
118
6
4
2
2
1
0
30
60
90
120
150
180
210
240
270
300
330
Days
Annane D. JAMA. 2010;303:341-348
Conventional
1
360
1
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;41:580–637
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%
20
18
16
14
12
10
8
6
4
2
0
17%
16.4%
8.7%
5.1%
4.1%
3.1%
7.8%
% Intensive insulin
therapy
6.8%
2.7%
0.8%
IIT
TS
NI
CE
-S
UG
AR
CO
TR
O
L
CO
N
P
G
LU
VI
SE
II
0.5%
N
I
LE
UV
E
N
LE
UV
E
% Control
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;41:580–637
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;41:580–637
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;36:3062–3066
Khan AI. Arch Pathol Lab Med. 2006;130:1527–1532
Desachy A. Mayo Clin Proc. 2008;83:400–405
Fekih Hassen M. Diabetes Res Clin Pract. 2010;87:87–91
Dellinger P. Crit Care Med. 2013;41:580–637
Dellinger P. Intensive Care Med. 2013;39:165-228