L I TER AT U R E R EVIEW

Perioperative Hyperglycemia: A Literature

Review
Tammy S. Peacock, MAPSY, BSN, RN, NEA-BC, CENP, CPPS, CLSSBB

ABSTRACT
The purpose of this literature review is to examine current evidence and determine the effects of stress hyper-
glycemia on patient outcomes during the perioperative period. This review summarizes the pathophysiology of
stress hyperglycemia, the population it affects, and strategies for optimal treatment to reduce the potential for
postoperative complications. A literature search produced 16 of the most current studies on the effect of stress
hyperglycemia in both the diabetic and nondiabetic populations. The evidence presented indicates the need to
maintain tight glucose control in the perioperative patient. Although there are varying approaches to managing
stress hyperglycemia, there is compelling agreement that stress hyperglycemia should be treated in all surgical
patients.

Key words: stress hyperglycemia, glucose control, surgical site infection, insulin resistance.

H yperglycemia is strongly correlated with

increased mortality and morbidity in patients
undergoing surgery.1-12 In addition, undiagnosed
insulin resistance is progressively more common on the
day of surgery.13 Perioperative hyperglycemia is a normal
glucose management or the glucose management of out-
patient surgical patients.

response to surgery and affects diabetic patients more
than nondiabetic patients.2 Perioperative-­induced stress
hyperglycemia has been linked to several postoperative
complications, including sepsis, myocardial infarction,
surgical site infection (SSI), and death.2 Perioperative
stress hyperglycemia can occur in patients admitted for
various types of surgical procedures, including general,
cardiac, vascular, and orthopedic surgery.2 Insulin admin-
istration may attenuate some of the perioperative risks
of hyperglycemia; however, target perioperative blood
glucose levels remain controversial.14 Tight periopera-
tive glucose control with insulin may cause hypoglycemic
events, which also are related to poor clinical outcomes
and mortality.9 Although hypoglycemia can be treated, it
is sometimes a complicated condition because the signs
are difficult to notice under anesthesia.15 Current stud-
ies address intraoperative and postoperative periods, but
limited research has been done to address preoperative
PURPOSE
This literature review critically appraises and synthesizes
the evidence regarding the effects of stress hyperglyce-
mia in the perioperative period, reviews hyperglycemic
treatment modalities, and correlates hyperglycemia with
surgical complications using the most recent randomized
control studies from the past five years. The research
question was as follows: What are the recommended
treatment options for perioperative stress hyperglycemia
in inpatients and outpatients?
RESEARCH METHODS
I used key words to guide the search on October 20, 2017,
for each of the following databases: Cumulative Index to
Nursing and Allied Health Literature (CINAHL), PubMed,
and Scopus. I entered subject subheadings and word trun-
cations according to the individual database requirements
and limited the search to literature published in English

http://doi.org/10.1002/aorn.12445
© AORN, Inc, 2019
80 AORN Journal 
January 2019, Vol. 109, No. 1
from September 2011 through September 2017. The fol-
lowing individual search terms were used and included:
stress hyperglycemia, glucose control, surgery, perioperative,
surgical complications, tight glucose control, preoperative,
inpatient, outpatient, morbidity, and mortality.
For this review, I limited eligible studies to those that com-
pared any type of glucose control in adult surgical patients
with surgical complications. I excluded animal studies,
­laboratory-only studies, editorials, and conference presen-
tations. The original search yielded 279 full-text articles.
I removed duplicates, compared the remaining articles
against the exclusion criteria, and removed additional stud-
ies that did not meet the inclusion criteria (Figure 1). The
remaining 16 studies were included in this review. I evalu-
ated and appraised these studies according to the strength
and quality of the evidence using the AORN Research and
Non-­Research Evidence Appraisal Tools,16 and assigned an
appraisal score for each article (Supplementary Table 1).
PATHOPHYSIOLOGY OF STRESS
HYPERGLYCEMIA
The causes of hyperglycemia in the perioperative period
are multifactorial. An increase in sympathetic stimulation
in addition to a rise in cortisol, glucagon, catecholamines,
and growth hormone occurs during physiologic stress,
Figure 1. Flow chart showing the different phases
of the systematic review.
Perioperative Hyperglycemia
causing disproportionate release of inflammatory cyto-
kines.17 Cortisol stimulates protein catabolism and hepat-
ic glucose production. This increase in counter-­regulatory
hormones (ie, glucagon, growth hormones, cortisol) ini-
tiates a proliferation in endogenous glucose production
via gluconeogenesis (Figure 2).3 During the perioperative
period, impaired insulin signaling and transient insulin
resistance are believed to contribute to hyperglycemia in
patients with and without diabetes mellitus.3 This period
of impaired insulin signaling and transient insulin resis-
tance is believed to occur because of counter-­regulatory
hormone production and an excess of circulating proin-
flammatory cytokines.3 The literature indicates that tran-
sient hyperglycemia is the body’s response to decreased
circulating insulin levels and is most prominent on the first
day after an operation; however, it may continue for days.3
Surgeries involving the abdomen and thorax have been
correlated with a more prolonged and pronounced degree
of hyperglycemia. Furthermore, less invasive (eg, laparo-
scopic) procedures have been related to less increase in
insulin resistance.3
Preoperative carbohydrate loading as advocated by the
Enhanced Recovery After Surgery program may counter-
act the state of insulin resistance in surgical patients.14
The use of carbohydrate-­rich drinks avoids the catabol-
ic rate associated with starvation. Carbohydrate loading
also has been shown to increase insulin sensitivity, which
decreases the risk of postoperative hyperglycemia.18 A
neuroendocrine stress response, which releases counter-­
regulatory hormones, is a result of anesthesia and the
surgical procedure. The scale of this counter-­regulatory
response is weighted by the type of anesthesia and the
severity of the surgical procedure.19
FINDINGS
The studies in this review pertained to treating periop-
erative hyperglycemia, assessing the appropriate target
level of blood glucose, and monitoring patient outcomes
of hyperglycemia induced by surgical stress. Some of the
studies were performed in patients with diabetes and
some in patients without diabetes, and some studied both
populations simultaneously.
In 2008, Umpierrez et al4 initiated a randomized controlled
trial (RCT) that compared the efficacy of types of periop-
erative hyperglycemic control and documented the out-
comes of study participants. Participants were excluded if
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Peacock
Figure 2. Chart detailing the hormonal response to surgical stress.
they were pregnant, had liver disease, had impaired renal
function, underwent cardiac surgery, had a history of dia-
betic ketoacidosis, or had any mental condition that made
them unable to consent. The group was randomized into
two different groups. The researchers compared the inpa-
tient management of general surgery patients with type 2
diabetes who were treated with basal-­bolus glargine once
daily and glulisine before meals if they were able to eat
with a similar group of patients who were treated with
sliding scale insulin four times a day. The results revealed
that basal-­bolus glargine showed significantly better gly-
cemic control in patients with type 2 diabetes. The trial
also showed a lower frequency of postoperative compli-
cations (eg, systemic or localized infections, organ failure)
for this group.4
In 2015, Umpierrez et al5 conducted an RCT to determine
the optimal goal for glycemic control in patients undergo-
ing coronary artery bypass graft surgery. The researchers
randomized a pool of 302 patients into two equal-­sized
groups: an intensive control group with a glucose target
of 100 mg/deciliter (dL) to 140 mg/dL and a conservative
control group with a glucose target of 141 mg/dL to 180
mg/dL. Findings from the study showed little significant
difference in the rate of complications among the two
groups of the diabetic population (49% for the intensive,
82 AORN Journal 
January 2019, Vol. 109, No. 1
48% for conservative, P = .87). The study indicated that
complications among patients without diabetes were
significantly lower in the intensive control group using
a target glucose level of between 100 mg/dL and 140
mg/dL compared with the conservative control group
using a target glucose level of between 141 mg/dL and
180 mg/dL (34% and 55% respectively, P = .008).5
Bláha et al6 also looked specifically at tight glucose con-
trol (TGC) in nondiabetic patients aged 18 to 90 years who
underwent major cardiac surgery between 2007 and 2012.
There were two study groups: the perioperative group (n
= 1134) and postoperative group (n = 1249). There also
were two target ranges for blood glucose control: TGC
(blood glucose of 4.4 millimoles [mmol]/L to 6.1 mmol/L)
and glucose control (blood glucose of 4.4 mmol/L to 8.3
mmol/L).6 The perioperative group showed a marked
decrease (23.2%) in postoperative morbidity compared
with the postoperative study group (34.1%; relative risk,
0.68; 95% CI, 0.60 to 0.78). The reduction in postopera-
tive morbidity connected with the intraoperative initiation
of TGC was predominately driven by nondiabetic patients.6
Akbarzadeh et al7 conducted an RCT that investigat-
ed the effect of a new metabolic conditioning supple-
ment on nondiabetic coronary artery bypass patient
January 2019, Vol. 109, No. 1
outcomes. The supplement was composed of L-­carnitine
(3 g), vitamin C (750 mg), glutamine (15 g), selenium (150
μg), and vitamin E (250 mg), and was designed exclusive-
ly for this study. For this RCT, 89 nondiabetic patients
with an ejection fraction greater than 30% and who
were scheduled for coronary artery bypass grafting were
divided into four groups. Groups received either the
supplement, a placebo, or a combination of supplement
and placebo before and after surgery.7 The groups were
assigned as follows:
1. supplement before surgery and placebo after surgery
(n = 27),
2. placebo before surgery and supplement after surgery
(n = 26),
3. supplement both before and after surgery (n = 26), and
4. placebo both before and after surgery (n = 26).
These researchers found that when they compared the
results of the groups, all showed an increase in glucose
postoperatively; however, the placebo group showed the
highest increase. The patients who used the supplement
both before and after maintained better controlled blood
glucose levels during the perioperative period (P = .004).7
Patient Outcomes of Stress-­Induced
Hyperglycemia
Richards et al11 studied the relationship between stress-­
induced hyperglycemia and postoperative infections of
187 trauma patients who sustained orthopedic injuries.
The patient population they studied did not have a history
of diabetes and the target blood glucose level for these
intensive care unit patients was between 80 mg/dL and
110 mg/dL. Results of this study indicated that the risk for
an SSI was increased in patients with hyperglycemia being
treated for orthopedic injuries (P = .047).11
Kiran et al20 studied the effect of hyperglycemia in a non-
diabetic colorectal surgery patient population. This study
was retrospective and included 16,404 postoperative glu-
cose measurements in 2,447 patients. Of this group, 66%
showed elevated glucose levels above 125 mg/dL. This
study showed septic complications and mortality were
associated with hyperglycemia. Hyperglycemia also was
associated with both infectious and noninfectious com-
plications, with correlation increasing for patients with an
increasing American Society of Anesthesiologists class and
the severity of blood loss.20
Perioperative Hyperglycemia
Treatment Recommendations
There are many different recommendations about glu-
cose control in the literature, and some of the recom-
mendations vary regarding the appropriate level of
glucose control. The University of Washington Medical
Center used a very tight glycemic control protocol that
began with an insulin infusion with a glucose concen-
tration of greater than 140 mg/dL to maintain a target
glucose level of 100 mg/dL to 140 mg/dL. The proto-
col used four separate algorithms: one for type 1 dia-
betic patients, one for type 2 diabetic patients, and two
for patients in which the target glucose level did not
decrease by a prescribed amount. Intraoperative glu-
cose was measured by a point-­of-­care test completed by
anesthesia providers.8,21
There are many different recommendations
about glucose control in the literature, and
some of the recommendations vary regarding
the appropriate level of glucose control.
A study by Takesue and Tsuchida9 at the Hyogo College
of Medicine divided a patient population into surgical
patients and critically ill surgical patients. The goal for the
surgical patients was to maintain a glucose level of 110
mg/dL to 150 mg/dL, and for critically ill patients, the goal
was a glucose level of 140 mg/dL to 180 mg/dL. This study
resulted in a recommendation for both groups of patients
to start an insulin infusion when the patient’s glucose
reached >150 mg/dL.9
Evans et al10 reviewed studies completed between 2001
and 2008 and differentiated between noncritically ill and
critically ill surgical patients. Based on the information
from the studies, these researchers recommended the
use of subcutaneous insulin bolus therapy with a sliding
scale to maintain blood glucose between 140 mg/dL and
180 mg/dL in the noncritically ill surgical patients when
the fasting blood glucose was greater than 140 mg/dL
or random blood glucose was greater than 180 mg/dL.
The researchers recommended that the insulin infusion
for critically ill patients should be started with a blood
glucose level greater than 180 mg/dL with the goal of a
blood glucose of 140 mg/dL to 180 mg/dL.10 Researchers
­investigated another treatment option for perioperative
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Peacock January 2019, Vol. 109, No. 1

Key Takeaways
 Stress hyperglycemia not only affects postoperative morbidity and mortality in diabetic perioperative
patients, but also in nondiabetic perioperative patients.

 Tight glucose control during the perioperative period is supported by available evidence.

 Perioperative hyperglycemia may be treated with either subcutaneous insulin or an IV insulin infusion.

 Additional research is needed to develop hyperglycemia treatment recommendations for both inpatients
and outpatients.

hyperglycemia in which they did not divide the patients,
but treated patients with a blood glucose of 140 mg/dL
to 180 mg/dL with subcutaneous insulin and then initiat-
ed insulin infusion for those with a blood glucose greater
than 180 mg/dL.5
DISCUSSION
The evidence presented in these studies shows a clear
relationship between the level of glycemic control and
complications after surgery. Most studies were based
on cardiac, complex general, and orthopedic surgeries.
In the orthopedic study, musculoskeletal trauma sug-
gests a greater effect on hyperglycemia and increased
rate of SSIs.11 The studies that investigated outcomes
of hyperglycemia concluded that nondiabetic patients
were at greater risk for poorer outcomes than diabetic
patients. Even with evidence to provide glucose control,
compliance among anesthesia professionals is poor, pos-
sibly because of fear of a hypoglycemic effect.8,21 Many
of the studies supported the need for perioperative
glucose monitoring,1,2,5,6,8,10,14,20,21 and additional studies
showed a correlation between random elevated blood
glucose readings and postoperative complications.12,20
Perioperative nurses and leaders continue to struggle
with the question of how to encourage compliance with
blood glucose monitoring and initiation of treatment
when the evidence shows that the risk of adverse out-
comes is significant for both diabetic and nondiabetic
populations.
Additional research is needed to reach a consensus on
standardizing treatment practice for perioperative hyper-
glycemia. Standardized treatment recommendations may
provide better guidance for providers to comply with pro-
tocols to treat hyperglycemia. Currently there are oper-
ational challenges with using IV insulin. More surgeries
are being moved to outpatient facilities, which may not
have the resources to assess and treat hyperglycemia.
The existing protocols are directed toward inpatient facil-
ities and have great variation on the best methodology
of glucose control. As the number of inpatient surgeries
moving to the outpatient arena increases, the need for
facility leaders to develop outpatient perioperative hyper-
glycemic management protocols to decrease the risk of
postoperative complications also increases. There is a
need for more hyperglycemic research in the outpatient
environment.
Akbarzadeh et al7 discussed the effect that glutamine
and arginine can have on controlling insulin resistance by
metabolic regulation and postoperatively by decreased
cell injury, increased peripheral glucose utilization, and
increased antioxidant capacity. A newly recognized
L-­carnitine, which is used as an adjunct therapy for type
2 diabetes, showed efficacy in controlling insulin resis-
tance by means of increased fatty acid oxidation.7 This
therapy might have a positive effect on the treatment
of outpatient surgical patients because it may provide
adequate glycemic control without interfering with the
operational needs of the perioperative space.
LIMITATIONS
This literature review had some limitations, including a
small sample size, single institution used, first study for
a newly developed medication, limitations on surgery
type, and a single researcher reviewing and scoring arti-
cles. Another limitation of this review was the exclusion
of non–­English language literature because of the lack of
interpretation services. In addition, one study that was
conducted more than five years ago was included in this
review because it is considered an important reference to
perioperative hyperglycemia.

84 AORN Journal 
January 2019, Vol. 109, No. 1
CONCLUSION
Perioperative hyperglycemia has a significant correlation
with adverse surgical outcomes, and blood glucose should
be monitored in both the diabetic and nondiabetic surgi-
cal patient populations. The literature shows a need for
a standard treatment protocol for perioperative hyper-
glycemia in all surgical patients regardless of surgical
specialty. Whether critically ill patients should have dif-
ferent treatment standards than the general population is
unknown. Standards for the treatment of hyperglycemia
could increase compliance with treatment protocols and
lessen the fear of hypoglycemia. The literature lacked
any recommendations for outpatient surgical patients,
which is a concern because of the increase in surgical
procedures being performed in outpatient settings. The
risk for perioperative hyperglycemia exists in all patients
and should be monitored and treated to prevent adverse
­surgical complications.
Editor’s notes: CINAHL, Cumulative Index to Nursing and
Allied Health Literature, is a registered trademark of EBSCO
Industries, Birmingham, AL. PubMed is a registered trade­
mark of the US National Library of Medicine, Bethesda, MD.
SCOPUS is a registered trademark of Elsevier BV, Amsterdam,
the Netherlands.
SUPPORTING INFORMATION
Additional information may be found online in the sup-
porting information tab for this article.
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Tammy S. Peacock, Master of Arts in Health Psycho­
logy (MAPSY), BSN, RN, Nursing Executive Advanced,
Board Certified (NEA-­BC), Certified Executive in Nursing
Practice (CENP), Certified Professional in Patient Safety
(CPPS), Certified Lean Six Sigma Black Belt (CLSSBB),
is the surgical outcomes improvement leader at Kaiser
Permanente in Oakland, CA. Ms Peacock has no declared
affiliation that could be perceived as posing a potential
­conflict of interest in the publication of this article.