455
Comparison of Admission Serum Glucose
Concentration With Neurologic Outcome in
Acute Cerebral Infarction
A Study in Patients Given Naloxone
Harold P. Adams Jr., MD, Charles P. Olinger, MD, John R. Marler, MD,
Jose Biller, MD, Thomas G. Brott, MD, William G. Barsan, MD, and Karla Banwart, RN
Downloaded from http://stroke.ahajournals.org/ by guest on July 12, 2017
We studied the ability of serum glucose concentration and neurologic deficits at admission in predicting
the outcome of acute cerebral ischemia in 65 patients given naloxone. Among our patients, the volume
of infarction on computed tomograms and outcome were strongly related to the severity of neurologic
deficits found at admission. Neither a history of diabetes nor hyperglycemia when added to the results
of the initial neurologic assessment improved prediction of outcome after acute cerebral infarction.
(Stroke 1988; 19:455-458)
D
iabetes mellitus is an important risk factor for
ischemic cerebrovascular disease. Besides increasing the likelihood of a stroke, the presence of diabetes mellitus or hyperglycemia may
aggravate the severity of the acute ischemic event. In
two series, in-hospital mortality after cerebral infarction was greater among diabetic than among nondiabetic patients. u In a retrospective study, Pulsinelli et
al3 noted that cerebral infarction was worse among
patients whose glucose values were >6.6 mmol/1.
Other studies suggest that "reactive hyperglycemia" is
due to the major stress of the vascular event and is a
marker for poor prognosis.4-5 However, other studies
could not find a correlation between serum glucose
concentration at admission and either the subsequent
course or mortality of cerebral infarction.67 One study
noted that hyperglycemia combined with a normal
grycosilated hemoglobin may suggest poor prognosis
after stroke.7 The relations between serum glucose
concentrations and either the severity of stroke or its
outcome have not been established. We prospectivery
evaluated the ability of serum glucose concentrations
and neurologic deficits at admission to predict the
outcome of patients treated with naloxone within 48
hours of the onset of progression of cerebral infarction.
From the Division of Cerebrovascular Diseases, Department of
Neurology, University of Iowa, Iowa City, Iowa (H.P. A., J.B., K.B.),
the Departments of Neurology (C.P.O., T.G.B.) and Emergency
Medicine (W.G.B.), University of Cincinnati, Cincinnati, Ohio, and
the Stroke and Trauma Program, National Institute of Neurological and
Communicative Disorders and Stroke, Bethesda, Maryland (J.R.M.).
Presented in part at the Twelfth International Joint Conference on
Stroke and Cerebral Circulation, Tampa, Florida, February 26-28,
1987.
Supported by United States Public Health Service/National
Institutes of Health/National Institute of Neurological and Communicative Disorders and Stroke contracts NO1-NS-3-2324, TO1
(to the University of Cincinnati) and NO1-NS-3-22326, TO1 (to the
University of Iowa).
Address for reprints: Harold P. Adams Jr., MD, Division of
Cerebrovascular Diseases, Department of Neurology, University of
Iowa, Iowa City, IA 52242.
Received April 8, 1987; accepted December 23, 1987.
Subjects and Methods
Between May 1984 and November 1985,65 patients
were admitted to a study of naloxone for the treatment
of acute or progressing cerebral infarction. Patients
were treated within 48 hours of the latest progression
of symptoms at either the University of Cincinnati or
University of Iowa Hospitals. Patients with cerebral
infarction due to cardiogenic embolism, small vessel
arteriopathy (lacuna), large artery atherothrombosis, or
atheroembolism were treated. Diagnoses were made
using the criteria developed for the Harvard Cooperative Stroke Registry.8 Reasons for exclusion of prospective subjects have been described.9
Patients and relatives were asked about a history of
diabetes mellitus or any past treatment for elevated
blood glucose levels. Any management with glucosecontaining intravenous fluids was also noted. Serum
glucose concentration was among the blood studies
obtained upon admission to the hospital. Diabetes
mellitus or marked hyperglycemia were not reasons for
exclusion from this study. No food or glucosecontaining fluids were given during the 24 hours
of naloxone treatment. Insulin was administered
as clinically indicated to those patients with elevated
serum glucose concentrations. All patients received
naloxone in a regimen previously described.9 In the
previously reported dose escalation study, 27 patients
received doses of naloxone ranging from 2.5 to 200
mg/m2 loading dose. An additional 38 patients were
treated at Level VI (160 mg/m2 loading dose).10 Other
treatment included bed rest, supplemental oxygen, and
intravenous saline in a quantity to maintain adequate urinary output. Pretreatment medications were
continued.
Neurologic assessments were done at admission and
repeated frequently during the 24-hour naloxone infusion; 15 clinical parameters were independently
graded. For the purposes of this study, scores of the
assessed parameters were combined to give a total
score. A stroke was defined as mild when the total
456
Stroke
Vol 19, No 4, April 1988
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neurologic deficit score was <, 10, as moderate when
the score was 11-24, and severe if the total score was
£25. Neurologic deficits and outcome were assessed
at 7-10 days and 3 months after the stroke. Serum
glucose concentrations were measured at admission
and again at 24 and 48 hours and 7-10 days after the
stroke and categorized: s5.6,5.7-7.2,7.3-9.4, 29.5
mmol/1. Computed tomography (CT) was performed
before treatment and 7-10 days and 3 months after
treatment. The extent of any ischemic lesion seen on
CT was localized to anatomic structures and vascular
distributions using standard templates.11 Volume of
brain infarction on CT was determined using a computer program using digitizing methods, and patients
were grouped according to lesion volume on CT (> or
<50 cm3).
We compared neurologic deficit at admission, outcome, and CT lesion volume among diabetic and
nondiabetic patients and among patients grouped by
serum glucose concentration. Results were evaluated
for the influence of types of acute ischemia and CT
lesion volume. Outcomes among those patients with
hemispheric lesions in the distribution of the middle
cerebral artery (MCA) or its branches were separately
analyzed.
Results
Data were collected from 34 men and 31 women who
ranged in age from 40 to 84 (mean 64.4, median 64)
years. The interval from latest progression of neurologic symptoms to admission ranged from 0 to 41.5
(mean 6.22) hours. Sixty patients were seen within 24
hours of their ictus. On admission, neurologic deficits
were mild in 20 patients, moderate in 22, and severe
in 23. By 7-10 days, neurologic deficits were mild in
32 patients, moderate in 11, and severe in 19. Three
patients died as a result of their cerebrovascular events
within 10 days; their admission glucose concentrations
were 5.6, 5.9, and 10.8 mmol/1. By 3 months, 14
patients had recovered completely, 38 had recovered
partially, and 6 were stable. Four additional patients
had died by 3 months, all from nonneurologic causes.
In general, the degree of recovery was related to the
severity of signs noted on admission. Complete recovery occurred in nine of those 20 patients with mild
strokes but in none of those 23 with clinically severe
events.
Twenty-one patients were diabetic; eight were using
insulin and 10 were taking oral hypogrycemic agents
50
r
40
A
Severity
o
3°
(Stroke
Score)
20
10
o o
0
10
o
o
o
o
15
20
25
S5.6
5.7-7.2
7.3-9.4
2:9.5
Patients
Diabetic
Total
18
15
12
20
0
2
1
18
Complete
recovery
5
3
3
3
35
Serum Glucose (mmol/L)
FIGURE 1. Relation between serum glucose concentration at
admission and severity of neurologic deficits at admission in 65
patients. A, nondiabetic patient; o, diabetic patient. Score:
<,10, mild deficit; 11-24, moderate deficit; 2.25, severe
neurologic deficit.
before their vascular events. The outcomes of stroke
were similar among diabetic and nondiabetic patients.
On admission, serum glucose concentrations for all 65
patients ranged from 4.3 to 34.2 (mean 9.5, median
13.7) mmol/1 and among the diabetic patients from 6.2
to 34.2 (mean 15.4, median 13.7) mmol/1 (Figure 1).
The relation of admission glucose concentration to
outcome is shown in Table 1.
Twelve patients had lacunar infarctions; six of the 12
patients were diabetic. The neurologic deficits among
these patients were mild in seven and moderate in five.
All 12 patients survived; three recovered completely
and seven recovered partially. Serum glucose concentrations among the 12 patients were 5.0-22.0 (mean
9.4) mmol/1. Neither admission serum glucose concentration nor history of diabetes influenced outcomes
among these patients.
Large vessel thrombotic infarctions were diagnosed
in 42 patients and embolic events were diagnosed in 11;
44 of these were in the distribution of the MCA. Twelve
of these 44 patients with MCA distribution infarction
were diabetic; their glucose concentrations were
10.9-33.9 mmol/1. Neurologic deficits were mild in 4
patients, moderate in 2, and severe in 6. One diabetic
patient died of a massive infarction. Serum glucose
concentrations among the 32 nondiabetic patients with
MCA distribution infarction were 4.3-17.9 mmol/1;
neurologic deficits were mild in 4, moderate in 11, and
severe in 17. Two nondiabetic patients died. The degree
of recovery and neurologic condition among patients
with MCA distribution events were not influenced by
TABLE 1. Correlation of Serum Glucose Concentration at Admission and Volume of Infarction by Computed
Tomography With Outcome at 3 Months
Scrum
glucose
concentration
30
Outcome at 3 months
Partial
recovery
Stable
1
10
6
3
9
0
13
2
*1 patient died before second computed tomogram could be obtained.
Dead
2
3
0
2
Lesion volume (cm3)
Mean
Range
0-507.0
0-138.5
0-327.6
0-234.3*
105.0
39.5
64.0
44.1
Adams et al
600
500
400
Volume
of
Lesion
cm 3
300
AA
200
100
0
5
10
18
20
25
Serum Glucose (mmol/L)
FIGURE 2. Relation between serum glucose concentration at
admission and volume of lesions by computed tomography (CT)
in 63 patients. A, nondiabetic patient; o, diabetic patient.
Eleven patients had normal CT examinations; 2 did not have
delayed CT examinations.
Downloaded from http://stroke.ahajournals.org/ by guest on July 12, 2017
either admission glucose concentration or history of
diabetes mellitus.
CT examinations 7-10 days or 3 months after
treatment showed infarctions in 52 patients; 11 had
normal studies and one died before a second CT could
be obtained. Lesion volume ranged from 0 to 507 cm3
(Figure 2). Mean volumes of nonlacunar infarctions
were 36 cm3 in diabetic and 65 cm3 in nondiabetic
patients. The mean lesion volume was 105 cm3 among
18 patients (including those with a normal CT) with a
serum glucose concentration of <, 5.6 mmol/1 and 44.1
cm3 among 20 patients with a serum glucose concentration of a 9.5 mmol/1. Four of the five largest
infarctions as determined by CT were among patients
whose serum glucose concentrations were normal at
admission. Patients who arrived with the most severe
neurologic deficits had, in general, the largest lesions
byCT.
Discussion
Our experience suggests that neither history of
diabetes mellitus nor elevated serum glucose concentration at admission to the hospital is very helpful in
predicting the outcome of an acute ischemic cerebrovascular event or the size of infarction by CT. The
severity of neurologic deficits on admission and the
type of cerebral infarction remain the most important
prognostic factors. Most patients with mild strokes or
lacunar infarctions do well whether they are hypergrycemic or have a history of diabetes or not. Our results
are similar to those reported by other clinical
investigators.6'12
Our study does have limitations. Our primary
purpose was to evaluate the possible efficacy of
naloxone. Naloxone increases the acute insulin response to glucose, glucose disappearance, and secondphase insulin secretion.13 However, there is no evidence
of a selective benefit of naloxone for ischemic events
accompanied by hypergrycemia. Our patients who had
severe deficits had poor outcomes despite naloxone
therapy, a result not influenced by the presence of
hypergrycemia. Results in patients receiving drugs
other than naloxone will probably be similar.
Serum Glucose and Neurologic Outcome
457
Our study has several advantages compared with
previous clinical studies relating serum glucose concentration to outcome of acute cerebral infarction. We
prospectivery collected data in 65 intensively studied
patients admitted within hours after the onset of stroke.
The sample was representative of the population of
acute cerebral infarction. The neurologic and CT
examinations were performed at standardized time
intervals, and the examinations were analyzed quantitatively.
Hypergrycemia at the onset of cerebral ischemia in
animal models may influence the extent of brain
injury.14"17 However, not all animal models have shown
this effect.1819 Recently, Ginsberg et al" reported that
hypergrycemia may lessen the extent of one type of
experimental brain infarction. Even if hypergrycemia
at the onset of cerebral ischemia affects prognosis,
using the glucose concentration at admission to predict
that at the onset of stroke is a practical impossibility in
most patients. The stroke may induce secondary
hypergrycemia, and patients may eat or be given
glucose-containing intravenous fluids because concern
about hypogrycemia causing focal neurologic deficits
often prompts administration of glucose to a diabetic
patient with an acute stroke.
The prognosis of stroke relates to the site and size
of cerebral infarction. The best prognostic factors
remain the cause of cerebral ischemia and the severity
of neurologic deficits. Concern about the potentially
adverse impact of hypergrycemia has already prompted
recommendations that serum glucose concentrations of
patients with acute stroke be kept in a near-normal
range.3-20 This recommendation is appropriate for most
acutely ill patients, regardless of whether they have had
a stroke. However, pending more convincing clinical
data, we question whether vigorous treatment of
hypergrycemia begun hours after the onset of stroke
will improve outcome.
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KEY WORDS
•
cerebral infarction
•
glucose
•
naloxone
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Comparison of admission serum glucose concentration with neurologic outcome in acute
cerebral infarction. A study in patients given naloxone.
H P Adams, Jr, C P Olinger, J R Marler, J Biller, T G Brott, W G Barsan and K Banwart
Stroke. 1988;19:455-458
doi: 10.1161/01.STR.19.4.455
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