Crit Care Nurs Q

Vol. 37, No. 2, pp. 182–187

Copyright c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

Acute Ischemic Stroke and

Hyperglycemia
Margaret E. Clark, BSN, RN; Jessica E. Payton, BSN, RN;
Laura I. Pittiglio, PhD, RN

To increase the comprehension about the profound effects of hyperglycemia within the first
48 hours poststroke on the outcomes of acute ischemic stroke, the authors reviewed multiple
studies and literature reviews. Research supports the detrimental effects of hyperglycemia on
the morbidity and mortality of patients diagnosed with acute ischemic stroke. The studies that
were examined revealed that although further research is necessary, controlling hyperglycemia is
overall beneficial to support superior clinical outcomes. The purpose of this article was to discuss
the importance of not only glucose control but also the vital role of nurses in controlling glucose
levels efficiently and immediately during the first 48 hours poststroke. Key words: acute ischemic
stroke, hyperglycemia, intravenous insulin, nursing implications, outcomes

T HE CENTERS for disease control and

prevention1 reports that stroke is a lead-
ing cause of mortality in the United States,
causing the deaths of 130,000 Americans
per year. Multiple sources emphasize that
hyperglycemia significantly contributes to
poor outcomes in patients with acute is-
chemic stroke.2-10 According to the American
Heart Association and the American Stroke
Association,11 hyperglycemia is defined as
a glucose level greater than 108 mg/dL.
Upon hospital admission, 43% to 68% of
patients diagnosed with ischemic stroke have
hyperglycemia.3 Furthermore, a study by
Fuentes et al12 found that 20% of patients
with euglycemia on admission developed
hyperglycemia later during their hospitaliza-
tion. Therefore, newly admitted patients have
Author Affiliations: Oakland University, Troy
(Ms Clark); Oakland University, White Lake
(Ms Payton); and Oakland University, Rochester,
Michigan (Dr Pittiglio).
The authors have disclosed that they have no signif-
icant relationships with, or financial interest in, any
commercial companies pertaining to this article.
Correspondence: Margaret E. Clark, BSN, RN, 4358
Willow Creek, Troy, MI 48085 (clarkiern@gmail.com).
DOI: 10.1097/CNQ.0000000000000015
182
the potential to experience hyperglycemia
anytime during their hospitalization that
ultimately may affect their prognoses. Closely
monitoring glycemic levels in patients with
acute ischemic stroke during their entire
hospital stay and not solely on admission is
necessary to optimize and improve patient
outcomes.
The physiological stress of an acute illness
such as stroke leads to a hypermetabolic state
that causes hyperglycemia by promoting
insulin resistance and impairing pancreatic
beta cell function. Therefore, hyperglycemia
activates the body’s inflammatory response
and accelerates neurological injuries in
patients with ischemic stroke.2,3 Within the
first 48 hours poststroke, hyperglycemia
has shown to worsen acute ischemic brain
injury by increasing brain edema, causing
hemorrhagic transformation and brain her-
niation, potentially resulting in death.2,4
Furthermore, an analysis of different studies
was completed to examine the relationship
between hyperglycemia and stroke. This
investigation highlighted that insulin has anti-
inflammatory properties thereby promoting
vasodilation, improving blood flow, and aid-
ing in tissue repair, all of which are essential
for the rehabilitation of these patients.13 As
a means of circumventing the detrimental

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Acute Ischemic Stroke and Hyperglycemia
outcomes associated with hyperglycemia, the
importance of early, aggressive intervention
is emphasized. In addition, possible treatment
options and interventions for patients with
acute ischemic stroke within the imperative
48 hours poststroke are also discussed.
REVIEW OF THE LITERATURE
In response to an acute illness, the body re-
leases catecholamines that have a systemic ef-
fect such as the activation of the inflammatory
cascade, electrolyte imbalances, immune sys-
tem dysfunction, oxidative injury, and mito-
chondrial dysfunction.2,3 As a consequence of
these processes, elevated lactate levels trigger
free-radical formation that results in neuronal
and glial damage.4 Because of the increased
glutamate concentration secondary to hyper-
glycemia, an excessive amount of calcium in-
flux occurs through ion channels resulting
in mitochondrial injury and cell death.4 Con-
sequently, these mechanisms not only con-
tribute to complications such as sepsis and
impaired wound healing but also exacerbate
neurological injuries associated with ischemic
stroke.4
Moreover, both human and animal studies
have supported the association between hy-
perglycemia and clinically inferior outcomes
for patients with acute ischemic stroke.5
Martini and Kent6 emphasized that the body’s
response to hyperglycemia causes inflamma-
tory, thrombotic, and vasoconstrictive reac-
tions. Because of these changes, detrimental
effects have been discovered to potentiate
neurological injuries. Capes et al7 highlighted
that hyperglycemia accelerates ischemic in-
jury, causes calcium overload that leads to
arrhythmias, and disrupts the blood-brain bar-
rier that promotes hemorrhagic conversion of
infarcts. The majority of studies have provided
strong evidence that hyperglycemia causes in-
creased infarct size, neuronal damage, hemor-
rhagic conversion, and decreased reperfusion
in acute ischemic stroke.2,4,7 In addition, stud-
ies have supported that hyperglycemia is as-
sociated with increased hospital mortality and
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
183
increased risk of poor functional recovery in
patients with ischemic stroke.2,7,14
Furthermore, animal studies have shown
that insulin not only reduces histological
injury but also improves neurobehavioral
outcomes.7 To assist in reversing the in-
flammatory properties of hyperglycemia,
neuroprotective insulin is used to not
only lower glucose levels but also support
reperfusion. While on a continuous insulin
infusion, patients’ C-reactive protein and
serum amyloid A protein levels were re-
duced significantly when compared with a
placebo.13 In critically ill patients, intensive
insulin therapy is suggested to maintain blood
glucose levels at or lower than 110 mg/dL to
reduce morbidity and mortality rates.15 This
would include intravenous insulin in lieu of
subcutaneous insulin with frequent glucose
monitoring every 1 to 2 hours. Based on pa-
tients whose glucose levels were aggressively
lowered, clinical outcomes were significantly
improved.5 Other benefits associated with
hyperglycemia correction included decreased
mortality rate, fewer bloodstream infections,
shorter time on the ventilator, and less critical
polyneuropathy.15 Therefore, it is crucial for
nurses to understand the benefits of glucose
control in the acute phases of stroke to not
only improve patients’ prognoses but also
decrease length of hospital stays.
Although studies conflict in recommended
thresholds in which glucose levels become
associated with worse clinical results, the
consensus among studies remains to treat
hyperglycemia for optimal outcomes. The
American Stroke Association11 proposes a
glycemic range 140 to 180 mg/dL whereas
the Glycemia in Acute Stroke study done by
Fuentes et al,12 found suboptimal outcomes
and a higher risk of death was associated
with a glucose level greater than 155 mg/dL.
The prospective consecutive cohort study
of Kruyt et al16 also determined that hyper-
glycemia (>7.0 mmol/L or >126 mg/dL)
was related to impaired executive function,
larger infarct size, and increased neurolog-
ical deficits in acute cortical infarcts. To
ensure optimal outcomes, the recommended
184 CRITICAL CARE NURSING QUARTERLY/APRIL–JUNE 2014
glycemic levels poststroke range from 70 to
155 mg/dL.2,12 Therefore, additional research
is needed to determine an overall therapeutic
glycemic range to provide optimal outcomes.
Currently, continuous intravenous insulin is
used to treat severe hyperglycemia in clin-
ical settings. To discover safe and practical
options to lower hyperglycemia, the ran-
domized pilot trials, The UK Glucose In-
sulin Trial and Treatment of Hyperglycemia
in Ischemic Stroke, examined the relation-
ship between hyperglycemia and treatment
options in ischemic stroke patients.9,17 The
UK Glucose Insulin Trial applied an intra-
venous administration of a mixture with in-
sulin, dextrose, and potassium to treat hy-
perglycemia known as glucose potassium
insulin (GKI).17 In this trial, GKI was shown
to be both practical and feasible in the treat-
ment of hyperglycemia for the first 24 hours
poststroke. The goal of this trial was to
maintain glycemic levels at 4 to 7 mmol/L
(72-126 mg/dL) in 933 participants.17 Accord-
ing to protocol, the nursing staff changed
the GKI regimen to maintain the specified
glycemic goal, and capillary blood glucose
monitoring was every 2 hours.17 Cardiovas-
cular signs also were checked every 4 hours
for the first 24 hours, and plasma glucose,
urea, and electrolytes were measured at base-
line, 24 hours, and 48 hours. Plasma glu-
cose was measured at 8 hours, 16 hours, and
24 hours from the start of infusion to ensure
a correlation with capillary monitoring.17 In
the GKI group, the overall mean plasma glu-
cose and mean systolic blood pressure were
significantly lower than those in the control
group. The mean difference in glucose was
0.57 mmol/L (P < .001), and the mean dif-
ference in blood pressure was 9.0 mmHg
(P < .0001).17 This trial lacked conclusive ev-
idence to lend support to significant clinical
benefits in terms of mortality and disability.
Nonetheless, the study provides a framework
for future research regarding the benefits of
aggressive glucose control in patients with
acute ischemic stroke.
The randomized, multicenter, blinded pilot
trial Treatment of Hyperglycemia in Ischemic
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Stroke found that hyperglycemia could be
treated safely without major adverse side ef-
fects using an intravenous insulin protocol.9
This trial included 46 patients with a cere-
bral infarction within 12 hours, a glycemic
baseline greater than or equal to 8.3 mmol/L
(≥150 mg/dL), and a National Institutes of
Health Stroke Scale score of 3 to 22.9 These
patients were randomized 2:1 to aggressive
treatment with continuous intravenous in-
sulin or to subcutaneous insulin 4 times daily.
In the aggressive treatment group, the tar-
get glucose levels were less than 7.2 mmol/L
(<130 mg/dL), and in the usual care group
with subcutaneous insulin, the target glu-
cose levels were less than 11.1 mmol/L
(<200 mg/dL).9 Glucose levels were moni-
tored every 1 to 2 hours, and treatments con-
tinued for 72 hours. The final clinical out-
comes were assessed at 3 months. Among
the participants, 31 patients had aggressive
treatment, and 15 patients had usual care.
Comparing the 2 groups, glucose levels were
significantly lower in the aggressive treat-
ment group throughout the 72 hours with
average blood glucose levels at 7.4 mmol/L
(133 mg/dL) whereas the usual care group had
average blood glucose levels at 10.5 mmol/L
(190 mg/dL).9 Hypoglycemia occurred only
in the aggressive treatment group at 35% with
13% having minimal symptoms.9 In conclu-
sion, this trial determined that intravenous in-
sulin protocol treated hyperglycemia during
acute cerebral infarction was significantly bet-
ter and without major adverse effects.
The randomized pilot trial called glucose
regulation in acute stroke patients (GRASP)
also supported that an insulin infusion for
patients with acute ischemic stroke is feasible
and safe by applying an insulin infusion
protocol.18 This trial applied continuous
infusion of Novolin brand insulin in normal
saline (1 U/1 mL) guided by eProtocol-insulin
system. Concurrently, 1-L D5NS with 20 mEq
potassium was delivered at 100 mL/h with
meal insulin (1 U/15 g carbohydrate). In each
of these trials, nurses played a vital role to en-
sure frequent glucose monitoring and proper
titration of insulin. Although subcutaneous
 Acute Ischemic Stroke and Hyperglycemia
sliding scale dosing corrects glycemic lev-
els, the GKI regimen assists in not only
maintaining euglycemia but also reducing
the risk of hypoglycemia.13 Nonetheless,
intensive insulin therapy is vitally important
in the monitoring of these patients and the
reduction of patient mortality rate.
Last, Paolino and Garner10 focused on
strict control of hyperglycemia that revealed
a dramatic decrease in hospital morbidity
and mortality, inpatient stays, hospital
costs, and neurological injuries. Because of its
pathologic effects on neurologic tissue, hyper-
glycemia continues to be a significant factor
in the evolution of an infarct and poor clinical
and functional recovery in stroke patients.
Applying both insulin treatment protocols,
multidisciplinary teams allow for rapid and
effective control of hyperglycemia.10 These
intravenous insulin protocols have been
proven to be superior to aggressively control
glycemic levels and therefore yield optimal
outcomes.10 The focus of evidence-based
research should be on the development of a
protocol as to how to administer intravenous
insulin in patients with stroke. Therefore,
future research should utilize already-existing
insulin protocols as frameworks to examine
the most efficient and safe way to maintain
euglycemia in patients with stroke. In addi-
tion, considerations to prevent hypoglycemia
should be incorporated into protocols by
specifying the frequency of blood glucose
checks and the insulin dosage based on glu-
cose levels. Because nurses are actively apply-
ing insulin protocols, research should include
the opinion of nurses in the development of
improved protocols. Furthermore, research
is needed to develop useful educational op-
portunities for nurses and nursing assistants
to emphasize the importance of aggressive
glucose control. Although staff resistance may
occur with this additional work, both hospital
and floor management should focus on pro-
viding support for staff with the implemen-
tation of improved protocols and techniques.
Bedside nurses continue to be at the forefront
of hyperglycemia control and therefore signif-
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
185
icantly impact the outcomes of patients with
stroke.
NURSING IMPLICATIONS
Based on the reviewed studies, hyper-
glycemia has been associated with poor clini-
cal outcomes for patients with acute ischemic
stroke. Both human and animal studies sup-
port that the unfavorable effects of hyper-
glycemia accelerate neurological injuries in
these patients.2-7,9,10 Multiple randomized pi-
lot trials also have revealed that continuous
insulin infusion is feasible and safe to treat hy-
perglycemia in acute ischemic stroke patients
with the concurrent infusion of dextrose and
potassium to avoid hypoglycemia.9,13,17,18 Al-
though more research is needed to define a
therapeutic glycemic range in these patients,
most research supports a therapeutic level
less than 155 mg/dL.2,9,12,15-17
Nonetheless, it is crucial for nurses to un-
derstand and be vigilant about the benefits
of aggressive glucose control in the acute
phases of stroke to prevent further compli-
cations. During the critical time period of
the first 48 hours poststroke, nurses should
closely monitor patients’ neurological, cardio-
vascular, and glycemic statuses to ensure op-
timal outcomes. Hospital protocols regarding
stroke should include capillary glucose mon-
itoring at least every 4 hours during the first
48 hours poststroke if not on continuous in-
travenous insulin. Furthermore, stroke proto-
col should include the initiation of contin-
uous intravenous insulin with dextrose and
potassium additives for patients with hyper-
glycemia (>155 mg/dL). Therefore, capillary
glucose monitoring would become more fre-
quent such as every 1 or 2 hours.8 Nurses
would be able to closely monitor patients’
glycemic levels and titrate the insulin ac-
cording to protocol in order to aggressively
lower glucose levels. Based on the litera-
ture, the recommended safe range is 72 to
155 mg/dL.2,9,12,15-17 Because of the labor-
intensive tasks with this infusion and need
for close monitoring, these patients should be
186 CRITICAL CARE NURSING QUARTERLY/APRIL–JUNE 2014
admitted to intensive care units or progres-
sive units where nurses are able to monitor
patients closely. These interventions would
ultimately improve patient outcomes and de-
crease mortality rate with the collaboration of
nurses.
CONCLUSION
The prevalence of hyperglycemia and
stroke reveals that this relationship is a
common dilemma. Studies have shown that
hyperglycemia promotes an inflammatory
response.6 This, in turn, causes decreased
reperfusion and increased infarct size, neuro-
logical deficits, cerebral edema, hemorrhagic
conversion, and mortality in patients.2,4,6,7
Intravenous insulin with dextrose and potas-
sium additives has been shown to be safe and
feasible in the treatment of hyperglycemia in
patients with acute ischemic stroke.9,13,17,18
In addition, insulin has demonstrated to
have anti-inflammatory properties and to be
neuroprotective against the harmful effects
REFERENCES
1. Centers for Disease Control and Prevention. Stroke
facts. http://www.cdc.gov/stroke/facts.htm. Pub-
lished October 17, 2012. Accessed February 16, 2013.
2. UCLA Stroke Investigators, for the UCLA Stroke In-
vestigatorsBruno A, Liebeskind D, Hao Q, Raychev R.
Diabetes mellitus, acute hyperglycemia, and ischemic
stroke. Curr Treat Opt Neurol. 2010;12(6):492-503.
3. Kavanagh BP, McCowen KC. Glycemic control in the
ICU. N Engl J Med. 2010;363(26):2540-2546.
4. Kagansky N, Levy S, Knobler H. The role of hyper-
glycemia in acute stroke. Arch Neurol. 2001;58(8):
1209-1212.
5. Bruno A. Management of hyperglycemia during acute
stroke. Curr Cardiol Rep. 2009;11(1):36-41.
6. Martini SR, Kent TA. Hyperglycemia in acute
ischemic stroke: a vascular perspective. J Cerebr
Blood Flow Metabol. 2007;27:435-451. doi:10.1038/
sj.jcbfm.9600355.
7. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein
HC. Stress hyperglycemia and prognosis of stroke
in nondiabetic and diabetic patients: a systematic
overview. Stroke. 2001;32(10):2426-2432.
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
of hyperglycemia. Therefore, continuous
intravenous insulin in correlation with an
insulin protocol should be used to sup-
port a therapeutic glycemic level of 72 to
155 mg/dL.2,9,12,15-17 Stroke protocol should
incorporate capillary glucose monitoring ev-
ery 4 hours for the first 48 hours poststroke.
Otherwise, patients should have glucose
monitoring every 1 to 2 hours if the intra-
venous insulin has been initiated. As patient
advocates, nurses on neuroscience intensive
care units or progressive units should closely
monitor these patients’ neurological and
cardiovascular statuses. Because of their vital
positions, nurses need to support educational
services regarding optimal monitoring pro-
tocols as well as guidelines for notifying the
physician or midlevel provider. Nursing inter-
ventions aimed at improving hyperglycemic
control within the critical care setting will not
only improve patient outcomes significantly
but also decrease morbidity and mortal-
ity rates in patients with acute ischemic
stroke.
8. Rowat A, Steele B, Morrow B. Using the mnemonic
“brain attack” in the management of acute stroke.
Nurs Stand. 2009;24(6):50.
9. Bruno A, Kent TA, Coull BM, et al. Treatment of hy-
perglycemia in ischemic stroke (THIS): A randomized
pilot trial. Stroke. 2008;39(2):384-389.
10. Paolino AS, Garner KM. Effects of hyperglycemia on
neurologic outcome in stroke patients. J Neurosci
Nurs. 2005;37(3):130-135.
11. Adams HP, del Zappo G, Alberts MJ, et al. AHA
statistical update: heart and stroke statistics—2013
update: a report from the American Heart As-
sociation. Stroke. 2007;38:1655-1711. doi:10.1161/
STROKEAHA.107.181486.
12. Fuentes B, Dı́ez-Tejedor E, Castillo J, et al. The prog-
nostic value of capillary glucose levels in acute stroke:
the GLycemia in acute stroke (GLIAS) study. Stroke.
2009;40(2):562-568.
13. McCormick MT, Muir KW, Gray CS, Walters MR.
Management of hyperglycemia in acute stroke: how,
when, and for whom? Stroke. 2008;39(7):2177-
2185.
 Acute Ischemic Stroke and Hyperglycemia 187

14. Wang Y, Lim LL, Levi C, Heller RF, Fisher J. Influ-
ence of hyperglycemia on stroke mortality. J Stroke
Cerebrovasc Dis. 2001;10(1):11-18.
15. Van den Berghe G, Bouillon R, Wouters P, et al. In-
tensive insulin therapy in critically ill patients. N Engl
J Med. 2001;345(19):1359-1367.
16. Kruyt ND, Nys GMS, van der Worp HB, van Zand-
voort MJE, Kappelle LJ, Biessels GJ. Hyperglycemia
and cognitive outcome after ischemic stroke. J Neu-
rol Sci. 2008;270(1):141-147.
17. Gray CS, Hildreth AJ, Sandercock PA, et al. Glucose-
potassium-insulin infusions in the management of
post-stroke hyperglycaemia: the UK Glucose In-
sulin in Stroke Trial (GIST-UK). Lancet Neurol.
2007;6(5):397-406.
18. Johnston KC, Hall CE, Kissela BM, et al. Glu-
cose regulation in acute stroke patients (GRASP)
trial: a randomized pilot trial. Stroke. 2009;40(12):
3804-3809.

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.