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GLYCEMIC CONTROL IN CRITICALLY ILL PATIENTS
ABSTRACT
Hyperglycemia in critically ill patients is not merely an adaptive
phenomenon to stress but it is also associated with increased risk
of morbidity & mortality.Various trials conducted since 2001 have
consolidated the fact that adequate management of uncontrolled
hyperglycemia resulted in better outcome in terms of decreased
morbidity, mortality and decreased ICU stay. But this has been
diluted by the fact that many recent trials like NICE-SUGAR study that
attempted to achieve normoglycemia (80-110mg/dl) have resulted in
increased mortality.
Insulin therapy should be initiated in most cases, usually by slow
IV infusion.There are various protocols for insulin therapy based
on insulin infusions and hourly/2 hourly blood glucose monitoring;
none of them have been found to be superior. Moreover one
protocol may not fit for all patients, so other issues like patient’s
pre-morbid conditions, individual response to insulin, ICU set up,
uniform blood glucose monitoring protocols, availability of trained
staffs etc. should be considered before choosing a protocol. Even
after completion of NICE-SUGAR and GLUcontrol study, the
exact target blood glucose level remains debatable but probably
it is reasonable to keep blood sugar around 150mg/
dl to balance the maximum benefit at the cost of minimum
hypoglycemic events, a major concern in tight glucose control.
We need to conduct large, methodologically sound multicenter
trials to ascertain which patient populations will benefit most from
intensive insulin therapy and to firmly establish the blood glucose
concentration at which maximum benefits will be realized. In the
mean time a moderate degree of glycemic control maintaining
levels mentioned above while avoiding extremes of hypoglycemia
and hyperglycemia seems reasonable.
Key words – Hyperglycemia, Hypoglycemia, critically ill patients,
insulin infusion therapy
INTRODUCTION
The beginning of the 21st century has witnessed the opening of
a new dimension in management of hyperglycemia in critically
ill patients, whether diabetic or non diabetic, that was treated
with neglectful glycemic control involving haphazard therapeutic
approaches (e.g., use of Insulin “sliding scales”) –a practice too
common just a decade ago. Though hyperglycemia is a common
problem encountered in critically ill patients, it was being ignored
as merely an adaptive phenomenon to stress hormones. Recent
Vijay Achari, Prit Pal Singh, Upendra Baitha
clinical data since the 1990s have shown that uncontrolled
hyperglycemia is associated with poor outcomes in hospitalized
patients (Table-1) [1-9]. In addition, post operative glucose levels
are a significant predictor of infection rates after cardiac surgery.
Various studies conducted since 2004 have shown clearly that
use of intensive insulin therapy to maintain tight blood glucose
control possibly decreases morbidity and mortality in surgical and
medical ICUs (Table 2). [10-13]
Significant alterations to glucose metabolism occur under
conditions of stress such as trauma, burn, major surgery, stroke,
acute MI and sepsis. Stress-induced hyperglycemia is the result
of increased sympathomimetic activity and increased release of
counterregulatory hormones and proinflammatory cytokines.
Insulin resistance and insulin secretory capacity in hospitalized
patients are affected by numerous factors, including the severity
of illness and medications (in particular, glucocorticoids and
pressors); in addition, the patient’s diet is often unpredictable
in the hospital, and tests and procedures frequently interrupt
both meal and medication schedules, further complicating the
management of glucose levels.The end result of these physiologic
changes is increased endogenous glucose production
coupled with insulin resistance that leads to stressinduced hyperglycemia (Figure-1). [14-17]
Patients receiving dextrose infusions,especially those administered
as part of parenteral nutrition are at highest risk for developing
hyperglycemia. However, other risk factors predisposing patients
to hyperglycemia are: sepsis, organ failure, surgical procedures,
pre-existing diabetes mellitus, acute pancreatitis, age and obesity,
as well as drugs such as catecholamine vasopressors (e.g.,
dopamine,norepinephrine),immunosuppressants (e.g.,tacrolimus,
cyclosporine), and corticosteroids. [18
EFFECT OF HYPERGLYCEMIA AND INSULIN IN
CRITICALLY ILL PATIENTs
Severe hyperglycemia has deleterious effects on vascular,
hemodynamic and immune systems, leading to increased
susceptibility to infections and increase morbidity and mortality
not only in diabetics but also in non-diabetic and newly diagnosed
hyperglycemic patients. Whether hyperglycemia is the cause or
Glycemic Control in Critically Ill Patients
Table 1 : Clinical Trials In Hyperglycemia Management in Critically Ill Patients
Trial Design (year)
Nonrandomized, retrospective (1997)[1]
Prospective, nonrandomized, cohort (1998)[2]
Prospective, cohort, blinded, case-control (2001)[3]
Prospective, randomized, controlled (2001)[4]
Retrospective, cohort (2002)[5]
Historic cohort (2003)[6]
Prospective, one center (2003)[7]
Retrospective, longitudinal, one center (2003)[8]
Nonrandomized,historic control(2004)[9]
Patient Population
Results
Diabetic and nondiabetic patients undergoing
Diabetic: higher deep sternal wound infection
cardiac surgery (n=8910, 1585 diabetic, 7325 non- rate before vs after protocol. Nondiabetic: higher
diabetic patients)
deep sternal wound infection rate before vs after
protocol.
Diabetic patients undergoing elective surgery
Higher infection rate (except for UTI) in patients
(n=93)
with BGL > 220 mg/dl vs BGL < 220 mg/dl on
post-operative day 1.
Patients with known DM, unknown DM, and non- Frequency of surgical site infections directly and
diabetic patients with hyperglycemia undergoing
significantly correlated with degree of hyperglyceCABG or cardiac valve procedure (n=1044, 300
mia during postoperative period. Higher surgical
with known DM, 700 with unknown DM, 44 DM
site infection rate in patients with known DM vs
status not mentioned; 74 infected, 970 control)
patients with unknown DM. Higher surgical site
infection rate in patients with known and unknown
DM and nondiabetic patients.
Diabetic and nondiabetic surgical ICU patients
Lower overall ICU mortality, lower mortality in
(n=1548, 765 intensive insulin, 783 conventional
patients in ICU > 5 days, lower overall in-hospital
insulin)
mortality, lower in-hospital mortality in patients
in ICU > 5 days, lower frequency of septicemia,
prolonged antibiotics, and bacteremia in intensive
vs conventional group.
Diabetic and nondiabetic patients undergoing
Diabetic: higher perioperative BGL correlated with
CABG(n=1090, 400 diabetic, 690 nondiabetic
higher deep sternal wound infection rate. Higher
patients)
postoperative infection rate (deep sternal wound
infection, donor site infection, UTI) in diabetic
vs nondiabetic patients. Higher early mortality in
diabetic vs nondiabetic patients.
Diabetic and nondiabetic patients undergoing
Higher overall infection rate in diabetic vs nondiaCABG (n=1574, 545 diabetic, 1029 nondiabetic
betics patients. Higher mortality in patients who
patients)
developed infection in both groups.
Diabetic and nondiabetic patients admitted to
In all glucose bands, increased insulin administration
cardiothoracic, cardio-respiratory surgery and
corresponded with significantly increased risk of
medicine ICU (n=523)
ICU death.
Diabetic and nondiabetic patients admitted to gen- Higher BGL corresponded with higher hospital
eral medical, surgical, and coronary ICU (n=1826) mortality.
Diabetic and nondiabetic surgical and medical ICU Lower hospital mortality after protocol implepatients (n=1600, 800 treatment group)
mentation. Infection rate similar before and after
protocol.
effect of acute illness is not yet known. It has been shown that
intensive insulin therapy exerts its powerful anti-inflammatory
effect through its role in functional improvement of insulin
sensitive organs through direct anabolic effect in acute illness
than promoting tissue repair, decreased free radical production,
and enhanced nitrous oxide synthesis, direct anabolic effect on
muscles, maintenance of phagocytic function and complement
system. [Table.3][19, 20]
glycemic control by maintaining blood glucose level below 110
mg/dl can prevent post operative infection, decrease associated
complications and reduce morbidity and mortality in critically ill
surgical patients. In 2003 Van den Berghe et al demonstrated that
even moderate hyperglycemia (110-150 mg/dl) was associated
with significant increased in risk of bacteremia. [21] However, trials
of tight blood glucose control in medical ICU patients have been
less impressive and a trial of blood glucose control in Germany
was stopped earlier because of an increased risk of harm (VISEP).
STUDIES PERTAINING TO GLYCEMIC CONTROL
IN ICUs (Table 1 & 2)
In Van den Berghes’ subsequent trial on 1200 patients in the
medical ICU who were predicted to stay for at least 3 days,
in-hospital mortality was 37.3.% in the intensive-treatment
group vs. 40 % in the conventional-treatment group; [p=0.33]were
not significantly different although complications were
less[hospital stay, renal failure] in the intensive-treatment group
but the subgroup analyses indicated that. the greatest benefit
The earliest landmark trial was done by Van den Berghe et al
in surgical ICU patients in 2001, which showed that intensive
insulin therapy was associated with a 34% decrease in overall
in-hospital mortality. The ICU mortality rate was decreased from
8% to 4.6% (42% reduction).(4)His study demonstrated that tight
51
Medicine Update 2010  Vol. 20
Decreased level of activity:
Physiological stress
Old Age
Sepsis
Increased counterregulatory hormones
Diabetes Mellitus
Cirrhosis
Pancreatitis
CKD
Increased proinflammatory
cytokines
Table 3 : Anti-Inflammatory Effects of Insulin
Drugs:
Dextrose containing fluid
TPN
•
•
•
•
• Decreased level of
Insulin
• Increased insulin
resistance
•
•
•
therapy as they enter the ICU. [10]
SEVERE HYPERGLYCEMIA
•
•
•
•
•
•
•
•
•
•
Counters the effect of low level of Mannose Binding Lectin (MBL)
Decreased C. Reactive Protein.
Decreased Pro-inflammatory cytokines.
Decreased Superoxide radical protection, Decreased Free radical
protection.
Increased Anabolic effect promoting tissue repair.
Increased Nitrous Oxide production.
Maintenance of Macrophage and Neutrophil function.
A meta-analysis of 35 randomized trials by Anastassios et al in
2004 concluded that insulin therapy in critically ill patients has
a beneficial effect on short term mortality in different clinical
settings. [22]
Increased Oxidative radicals.
Decreased Chemotaxis.
Decreased Phagocytosis.
Decreased Complement fixation.
Endothelial dysfunction.
Pro-coagulant state.
Immune Dysfunction
Decreased wound healing
Increased susceptibility to Infection.
Increased Cerebral & Myocardial Ischemia
The Diabetes Insulin–Glucose Infusion in Acute Myocardial
Infarction (DIGAMI) trial on 620 patients with Diabetes mellitus
and acute myocardial infarction showed that in the group receiving
intensive glycemic management one year mortality was 29% lower
than in group receiving conventional glucose control (18.6%
versus 26.1%, P=0.03).[23]However the DIGAMI-2 trial remained
inconclusive possibly because of inadequate number of patients
and inadequate glycemic control even in the tightly controlled
group.[24]
Aggravating acute illness leading to increased
risk of morbidity and mortality mmmortality.
Fig. 1 : Pathophysiology of Hyperglycemia in critically ill Patients
Table 2 : Recent trials – Changing concept of treatment
of hyperglycemia in critically ill patients.
Krinsley (2004) studied the effect of intensive management in
mixed surgical-medical ICU keeping target glucose level below
140 mg/dl with subcutaneous insulin regimen. Insulin infusion was
started only if blood glucose level exceeded 200 mg/dl. The inhospital mortality rate was significantly lower among patients
receiving intensive treatment than among controls (14.8% Vs
20.4%, P=0.002). [9]
Prospective, random- Surgical &medical ICU
ized, controlled,(2006)[10] patients assumed to
require stay at least for
3 days (n=1200)
Intensive insulin therapy
significantly reduced
morbidity but not mortality among all patients
in the medical ICU.
Prospective random- Twenty-nine random- Tight glucose control
ized controlled trials
is not associated with
ized controlled trial,
meta-analysis(2008)[11] totalling 8432 patients significantly reduced
admitted in ICU
hospital mortality but
(n=8432)
is associated with an
increased risk of hypoglycemia.
Intensive insulin therapy
Multicenter randomized, Adults with severe
sepsis &septic shock
placed critically ill patwo by two factorial,
(n=537)
tients with sepsis at inVISEP(2008)[12]
creased risk for serious
adverse events related
to hypoglycaemia.
adult medical and
Intensive glucose conParallel-group, ransurgical
trol increased mortality
domized, multicenter
patients admitted to the among adults in the ICU.
controlled
ICUs,
trial NICE-SUG(n=6104)
AR(2009)[13]
The position statement by a panel of American College of
Endocrinology (ACE), AACE, and American Diabetes Association
(ADA) (2004)[25-26], recommended that a pre prandial target level
of 110 mg/dl be set for the plasma glucose level of all hospitalized
patients regardless of a prior diagnosis of diabetes. These
statements remain controversial, because they extrapolate data
from the few trials involving critically ill patients done earlier and
are contrary to newer and larger trials like GLUcontrol & NICESUGAR study. It is likely that these recommendations will
be revised soon. [27]
Inzucchi in 2006 in his review on hyperglycemia management
in hospital setting concluded that blood glucose levels should
probably be maintained below 140 mg/dl and perhaps below 110
mg/dl. For patients in coronary care unit the reasonable goal may
be higher (up to 180 mg/dl) [Fig 2]. [27]
In the Glucontrol trial (2007), Perier et al compared the effect of
two glucose control regimens by insulin in ICU patients. Patients
were randomized to two subsets either with a goal blood sugar
of 80-100 mg/dl to 140-180 mg/dl. The goal to enroll 3500
patients had to be terminated prematurely due to occurrence
of adverse events [severe hypoglycemia] which was significantly
was seen among the 767 patients who actually remained
in the medical ICU for at least three days [mortality 43%
vs. 52.5%, p=0.009]. Unfortunately as there are no definite
criteria to predict the patient‘s stay in ICU at the time of admission,
it remains unclear which patient should receive intensive insulin
52
Glycemic Control in Critically Ill Patients
No. of
Patients
Type
of ICU
Blood Glucose Level
Targeted
Intensive
Glucose
Control
Conventional
Glucose
Control
Blood Glucose Level
Achieved
Intensive
Glucose
Control
Primary
Outcome
Conventional
Glucose
Control
Rate of Outcome
Intensive
Glucose
Control
milligrams per deciliter
180
Odds Ratio
(95% CI)
Conventional
Glucose
Control
percent
Leuven 1 (Van den Berghe et al. )
1548
Surgical
80-110
180-200
103
153
Death in ICU
4.6
8.0
0.58 (0.38–0.78)
Leuven 2 (Van den Berghe et al. )
1200
Medical
80-110
180-200
111
153
Death in hospital
37.3
40.0
0.94 (0.84–1.06)
Glucontrol (Devos et al., Preiser
J.C.: personal communication)
1101
General
80-110
140-180
118
144
Death in ICU
16.7
15.2
1.10 (0.84–1.44)
VISEP (Brunkhorst et al.)
537
General
80-110
180-200
112
151
Death at 28 days
24.7
26.0
Not reported
NICE-SUGAR
6104
General
81-108
144-180
118
145
Death at 90 days
27.5
24.9
1.14 (1.02–1.28)
160
Blood Glucose Level
(mg/dl)
Trial Name (Source)
Fig. 2 : Summary of recent clinical trials on intensive insulin
therapy in critically ill patients
Modified from Inzucchi S and Siegel M. N Engl J Med 2009;
360:1346-1349
Conventional glucose control
140
Intensive glucose control
120
108
100
more frequent in patients with tight blood glucose control group.
Perier concluded that tight blood glucose control with a target
range of 80-100mg/dl offered no apparent benefit but increased
risk of severe hypoglycemia. [28]
80
0
Base- 1
line
Brunkhorst et al (2008) in their VISEP Study found that the use of
intensive insulin therapy placed critically ill patients with sepsis at
increased risk for serious adverse events related to hypoglycemia
without any beneficial effect on patients’ outcome. the mean
morning blood glucose level was lower in the intensive-therapy
group (112 mg per deciliter [6.2 mmol/l]) than in the conventionaltherapy group (151 mg per deciliter [8.4 mmol/l], P<0.001).After
the first safety analysis, involving 488 patients, intensive insulin
therapy was terminated early by the data and safety monitoring
board, owing to an increased number of hypoglycemic events, as
compared with conventional insulin therapy.[12]
No. of Patients
Conventional control 2995
Intensive control
2989
2
3
4
5
6
7
8
9
10 11 12 13 14
Day after Randomization
2233
2260
1380
1428
909
908
583
562
Fig. 3 : Kaplan–Meier Scale shows mean blood glucose levels. Baseline data are the averages of the last blood glucose
measurement obtained before randomization; The dashed line
indicates 108 mg per decilitre, the upper limit of the target
range for intensive glucose control. [13]
patients] including NICE-SUGAR data showed no significant
benefit of intensive insulin therapy[risk of death 0.93] but
a significant risk of hypoglycemia. [29]
In the most recently published NICE-SUGAR Study (2009)
a multi-centric trial involving 6104 patients ,severe hypoglycemia
(blood glucose level, ≤40 mg per deciliter [2.2 mmol per liter])
was reported in 206 of 3016 patients (6.8%) in the intensivecontrol group and 15 of 3014 (0.5%) in the conventional-control
group (P<0.001).There was no significant difference between the
two treatment groups in the median number of days in the ICU
(P = 0.84) or hospital (P = 0.86). This result confirmed that
intensive glucose control, as compared with conventional
glucose control, increased the absolute risk of death at
90 days by 2.6 percentage points [27.5 % vs 24.9%]. They
have shown that a blood glucose target of <180 mg per deciliter
resulted in lower mortality than a target of 81 to 108 mg per
deciliter (fig 3).Whether the harm observed in this trial resulted
from the reduced blood glucose level, increased administration of
insulin, occurrence of hypoglycemia, methodologic factors specific
to the trial, or other factors remained unclear. The answer to
these important questions must await post hoc analyses of the
NICE-SUGAR study. Among questions raised on the credibility
of this study are uses of different glucometers having wide range
of fluctuations and undetected hypoglycemia, early withdrawal of
care, excess use of corticosteroids in patients in intensive glucosecontrol cohort leading to excess mortality.[13]. It is therefore likely
that moderately intensive glucose control[range of glucose
140-180 mg/dl] may produce better results in critically ill
patients than insisting on euglycemia as in the first Van
Den Berghe trial.
GLYCEMIC CONTROL IN CRITICALLY ILL
PATIENTS
Prevention
Prevention should be the first step in the management of
hyperglycemia. In patients receiving parenteral nutrition, the best
approach is to eliminate all other dextrose sources and start with
a low dextrose load and advance slowly substituting a portion
of the dextrose calories with lipids in parenteral nutrition helps
control the hyperglycemia. Normally, 20-30% of total daily calories
are provided as lipids.
Insulin therapy
A more recent meta analysis involving 26 trials [over 13,000
53
•
In ICUs/CCUs, continuous intravenous infusion of short
acting insulin is the preferred mode of glycemic control as
it allows rapid control of hyperglycemia and great flexibility
in appropriate dose adjustments (table 4). Several protocols
[4, 30-31]
are available for insulin therapy in ICU although there
is great variability regarding initiation and titration of insulin,
bolus dosing and method of insulin protocol adjustments.
None of these protocols have been shown to be superior,
having their own merits & demerits. One protocol may not
suffice for all patients mandating careful selection of protocol. [32] In the light of newer research more liberal
target glucose levels may be recommended.
•
As the patient’s clinical status improves the transition to
Medicine Update 2010  Vol. 20
Table 4 : Algorithm for Insulin Dosing to Achieve Normoglycemia in ICUs [van den Berghe protocol]
Blood Glucose Level Action or Adjust (mg/dl)
ment
On admission to ICU
< 220
Start insulin infusion
2-4 U/hr
110-220
Start insulin infusion
1-2 U/hr
< 110
Do not start insulin
infusion
During insulin infusion
> 140
Increase insulin infusion
by 1-2 U/hr
110-140
Increase insulin infusion
by 0.5-1 U/hr
Approaching normal
Adjust insulin dosage by
range
0.1-0.5 U/hr
Normal range
No change
60-80
Reduce insulin dosage
40-60
Stop insulin infusion,
ensure adequate
baseline glucose intake
< 40
Stop insulin infusion,
ensure adequate
baseline glucose intake,
administer
glucose 10-g intravenous boluses
Steeply falling
Reduce insulin dosage
by one half
While various studies conducted since 2001 have suggested
that proper management of hyperglycemia improves outcomes, the precise target blood glucose level, optimal mode of administration, type of insulin used
and the patients most likely to benefit remains uncertain.[34,35]
•
The response to optimal glycemic control immediately to
acute myocardial infarction and in septicemic patients is
highly erratic. Critically ill patients tolerate hypoglycemia
poorly and may remain asymptomatic during periods of severe hypoglycemia.
•
The benefits of insulin other than glucose control are also
not proven.
•
The trial by Van den Berghe in medical ICU patients[2006]
and failure of DIGAMI-2 trial to produce a positive
result have raised further doubts as to which level of intensive glucose control should be attained in ICU. This has
also been the finding of more recent trials[eg NICESUGAR, etc]
Frequency of Monitoring
Blood Glucose Level
Every 4 hrs
Every 1-2 hrs until in
normal range
Every 1-2 hrs until in
normal range
Every 1-2 hrs until in
normal range
Every 4 hrs
Recheck within 1 hr
Recheck within 1 hr
•
Many trials in critically ill patients are single centre, open
label trials[possibility of bias?]
Recheck within 1 hr
•
Could insulin itself have direct deleterious effects (sympathetic activation, sodium retention, or mitogenic actions)?
•
Did the well-recognized complexities of intensive management of glucose distract from other, ostensibly more important management practices in the ICU?[34-36] [10]
Every hr
SUMMARY & CONCLUSIONS
As recommended by the ADA (2005 &2008) [26,37], based on earlier
studies, blood glucose level in ICU patients should be maintained
below 150mg/dl and probably even below 110 mg/dl. However
NICE-SUGAR STUDY,VISEP and GLUcontrol studies have shown
no additional benefit in maintaining blood sugar level below
110mg/dl though post-hoc analysis is needed to validate findings
of NICE-SUGAR study in various sub-groups. Intravenous infusion
of insulin allows for more rapid titration in critically ill patients and is
always recommended for use in ICUs. The optimal glucose target
for critically ill patients is not yet ascertained or universally
accepted but a reasonable goal may be around 150mg/dl
(140-180mg in NICE-SUGAR study).[38]
subcutaneous insulin can be made with proper overlap between intravenous and subcutaneous insulin [at least ½-2
hours]. The dose should be adjusted according to latest infusion rate; total daily requirement being divided into basal
and prandial insulin dosing [usual ratio 1:1] supplemented
if needed by “correction dose” insulin. “Sliding scale” for
insulin therapy should be discouraged because of its
tendency to cause wide fluctuations in blood glucose level
and very poor glycemic control. [33]
•
•
Similar recommendations apply to hospitalized patients
with newly diagnosed hyperglycemia, although some patients may no longer require glucose-lowering therapy after
they have recovered from acute illness. Fasting glucose levels (and perhaps glycated hemoglobin values) should be reassessed 1 to 2 months after discharge in these patients, the
aim being to confirm [or refute] the diagnosis of diabetes.
An ideal protocol that leads to optimal glycemic control without
risk of hypoglycemia remains to be ascertained. The approach
should be to aim for target glucose level around 150 mg/dl not only
to circumvent concerns about hyperglycemia but also to minimize
risks of hypoglycemia. The most important part of glycemic
management of critically ill patients is proper glycemic control
under hospital setting in strict supervision of skilled professionals
and trained staff with regular (1-2 hrly) glucose monitoring and
adjustment of insulin infusion schedule.
CONTROVERSIES AND UNCERTAINTIES
While it is generally agreed that adequate glycemic control
is an essential part of ICU/critical care, there are still differences
among experts among the following points:-
Although the precise glucose targets for ICU patients remain
54
Glycemic Control in Critically Ill Patients
controversial, having a precise target may be less important than
recognizing that •
Hyperglycemia in critically ill patients whether diabetic or
not should be addressed properly.
•
Insulin therapy should be proactive, with frequent adjustments to optimize control;
•
One should avoid the twin dangers of hypoglycemia and
uncontrolled hyperglycemia both of which can have harmful
and possibly fatal consequences.
11. Wiener RS, Wiener DC, Larson RJ 2008 Benefits and risks of tight glucose control in critically ill adults. A meta-analysis. JAMA 300:933–944
12. Brunckhorst FM, Engel C, Bloos F, Meier-Hellmann A et al; German
Competence Network Sepsis 2008 Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139.
13. The NICE-SUGAR Study Investigators. Intensive versus conventional
glucose control in critically ill patients. N Engl J Med 2009;360:1283-97.
14. Knapke CM, Owens JP, Mirtallo JM. Management of glucose abnormalities in patients receiving total parenteral nutrition. Clin Pharm 1989;
8:136-44.
15. Mizock BA. Alterations in fuel metabolism in critical illness: hyperglycemia. Best Pract Res Clin Endocrinol Metab 2001; 15:533-51.
16. Wolfe RR. Carbohydrate metabolism in critically ill patients: implications for nutritional support. Crit Care Clin 1987;3:11-24.
KEY MESSAGES
•
Uncontrolled hyperglycemia as well as severe hypoglycemia is deleterious and must be avoided.
17. The ESICM Working Group. Metabolic basis of nutrition in intensive care unit patients: ten critical questions. Intensive Care Med
2002;28:1512-20.
•
Insulin infusion [iv] is required in most patients in ICU
with 1-2 hourly glucose monitoring.
18. McCowen KC, Malhotra A, Bistrian BR. Endocrine and metabolic dysfunction syndromes in the critically ill: stress-induced hyperglycemia.
Crit Care Clin 2001;17:107-24.
•
Optimal blood glucose in critically ill patients uncertain ?140-180 mg/dl.
•
Step down to basal –prandial-correction dose insulin [sc] when patient improves and oral feeding is
possible - no role of “sliding scale “insulin in hospital.
19. Hansen TK, Thiel S, Wouters PJ, Christiansen JS, van den Berghe G. Intensive insulin therapy exerts anti-inflammatory effects in critically ill
patients and counteracts the adverse effect of low mannose-binding
lectin levels. J Clin Endocrinol Metab 2003; 88:1082-8.
•
Patient may or may not require Insulin/OHA after discharge.
•
Glycemic targets <110 mg/dl in ICU? - More studies needed
on which sub-group benefits.
20. Groeneveld ABJ, Beinshuizen A,Visser FC. Insulin: a wonder drug in the
critically ill? Crit Care 2002; 6:102-5
21. Van den Berghe G, Wouters PJ, Bouillon R, et al. Outcome benefit of
intensive insulin therapy in critically ill patients: insulin dose versus glycemic control. Crit Care Med 2003; 31:359-66
22. Anastassios G. Pittas, MD; Richard D. Siegel, MD; Joseph Lau, MD Insulin
Therapy for Critically Ill Hospitalized Patients A Meta-analysis of Randomized Controlled Trials .Arch Intern Med. 2004;164:2005-2011.
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