Frequency of stress hyperglycaemia and its' influence on the outcome of patients with spontaneous intracerebral haemorrhage.

Abstract

To observe the frequency of admission hyperglycaemia and its influence on the outcome of patients with intracerebral haemorrhage.
This case series study included 450 consecutive patients received in medical wards at Liaquat University Hospital Jamshoro/Hyderabad with a diagnosis of Spontaneous Intracerebral Haemorrhage within 24 hours of their first stroke onset, between September 2006 to December 2008. The patients with haemorrhage secondary to brain tumours, trauma, haemorrhagic transformation of cerebral infarct, with previous history of haemorrhagic stroke, and patients with Glycosylated Haemoglobin greater than 8.5% were excluded from the study. Hyperglycaemia was defined as an admission or in-hospital fasting blood glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. The patients were divided into 2 broad groups, good outcome groups (i.e. patients who survived), and poor outcome group (patient died). Categorical variables such as age, sex, volume of haematoma, GCS score, presence of admission hyperglycaemia, Mean arterial pressure (MAP), and site of haematoma were expressed as percentage and frequency. Chi-square test was applied for comparing categorical variables such as hyperglycaemia, GCS score, and age with the outcome of the patients. Multivariate logistical regression analysis was done. A p-value 0.05 was considered as statistically significant. All calculations were done using SPSS version 16 (Chicago, IL, USA).
Of the 450 consecutive patients, 399 fulfilled the inclusion criteria. Males were 261(65.4%) and females 136 (36, 4%).Patients of over 65 years age numbered 222 (55.6%) and 177 (44.4%) were less than 65 years. Stress hyperglycaemia was present in 109 (27.3%) cases and 290 (72.7%) patients were normoglycaemic. Of the 109 patients who died during hospitalization, 59 (54.12%) had presented with admission hyperglycaemia (0.001).
Stress hyperglycaemia is a common finding in patients presenting with intracerebral haemorrhage. It is a marker of poor outcomes and higher mortality, more so in patients with no known history of diabetes.

Full text

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660 J Pak Med Assoc
Original Article
Frequency of stress hyperglycaemia and its' influence on the outcome
of patients with spontaneous intracerebral haemorrhage
Shaikh Samiullah, Rahoopoto Qasim, Shaikh Imran, Jaffery Mukhtair
Department of Medicine Liaquat University of Medical &Health Sciences, Jamshoro, Hyderabad.
Abstract
Objective: To observe the frequency of admission hyperglycaemia and its influence on the outcome of patients
with intracerebral haemorrhage.
Methods: This case series study included 450 consecutive patients received in medical wards at Liaquat
University Hospital Jamshoro/Hyderabad with a diagnosis of Spontaneous Intracerebral Haemorrhage within 24
hours of their first stroke onset, between September 2006 to December 2008. The patients with haemorrhage
secondary to brain tumours, trauma, haemorrhagic transformation of cerebral infarct, with previous history of
haemorrhagic stroke, and patients with Glycosylated Haemoglobin greater than 8.5% were excluded from the
study. Hyperglycaemia was defined as an admission or in-hospital fasting blood glucose level of 126 mg/dl (7
mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more
determinations. The patients were divided into 2 broad groups, good outcome groups (i.e. patients who survived),
and poor outcome group (patient died).
Categorical variables such as age, sex, volume of haematoma, GCS score, presence of admission
hyperglycaemia, Mean arterial pressure (MAP), and site of haematoma were expressed as percentage and
frequency. Chi-square test was applied for comparing categorical variables such as hyperglycaemia, GCS
score, and age with the outcome of the patients. Multivariate logistical regression analysis was done. A p-
value 0.05 was considered as statistically significant. All calculations were done using SPSS version 16
(Chicago, IL, USA).
Results: Of the 450 consecutive patients, 399 fulfilled the inclusion criteria. Males were 261(65.4%) and
females 136 (36, 4%).Patients of over 65 years age numbered 222(55.6%) and 177(44.4%) were less than
65 years. Stress hyperglycaemia was present in 109 (27.3%) cases and 290(72.7%) patients were
normoglycaemic. Of the 109 patients who died during hospitalization, 59(54.12%) had presented with
admission hyperglycaemia (0.001).
Conclusion: Stress hyperglycaemia is a common finding in patients presenting with intracerebral
haemorrhage. It is a marker of poor outcomes and higher mortality, more so in patients with no known history
of diabetes (JPMA 60:660; 2010).

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Introduction
Primary intracerebral haemorrhage (PICH) is defined
as bleeding that evolves within the tissue of the brain.
Primary non traumatic intracerebral haemorrhage (ICH)
comprises 10-15% of all strokes.1
Stress hyperglycaemia which is the presence of
hyperglycaemia without preexisting diabetes mellitus, is a
common problem in stroke population. It is estimated that
20%-50% of acute stroke patients present with a concurrent
diagnosis of hyperglycaemia.2Furthermore, hyperglycaemia
at the time of stroke in patients without a history of diabetes
mellitus has been linked to a poor prognosis in populations of
patients with cerebral haemorrhagic strokes.3As in patients
with ischaemic strokes acute hyperglycaemia is associated
with increased oedema and infarct size and with reduced
cerebral blood flow and cerebrovascular reserve,4it can be
postulated that hyperglycaemia can also increase ischaemic
brain damage around an ICH and therefore emerge as a
clinical predictor of worse prognosis in these patients. The
effects of admission hyperglycaemia on the clinical course
after intracerebral haemorrhage (ICH) are largely unknown,
and the few relevant studies have been limited by small size,
no distinction between diabetic and nondiabetic patients, or
lack for controls for other important clinical factors.5,6
The aim of this study was to observe the frequency of
admission hyperglycaemia and also the influence of
hyperglycaemia on the outcome of the patients with
intracerebral haemorrhage.
Patients and Methods
This case series study included 450 consecutive
patients received in medical wards at Liaquat University
Hospital Jamshoro/Hyderabad with a diagnosis of
spontaneous intracerebral haemorrhage (SICH) within 24
hours of their first stroke onset, between September 2006 to
December 2008. Informed consent was obtained from all
patients included or their legal representatives. Patients
information regarding biodata, clinical presentation and
laboratory workup was documented in a proforma. SICH was
defined as a neurological deficit documented by a brain
computed tomography (CT) indicating the presence of an
ICH in absence of trauma or surgery.7The patients with
haemorrhage secondary to brain tumours, trauma,
haemorrhagic transformation of cerebral infarct, with
previous history of haemorrhagic stroke, and patients with
HBA1C greater than 8.5% were excluded from the study. All
patients were screened according to a strict protocol
consisting of a complete medical history, a full neurological
examination, standardized blood tests, and a CT scan of the
brain within 24 hours. The Glasgow Coma Scale (GCS)
assessed initial stroke severity, and it was determined after
initial evaluation and resuscitation.8The patients were
categorized in to three groups. Group 1had GCS score 3-4,
group two with GCS 5-12 and group three with GCS >12.
The following data were collected: age, sex, recognized risk
factors for SICH (arterial hypertension, alcohol intake,
smoking, diabetes mellitus, serum cholesterol levels,
antiplatelet treatment), glucose levels at admission and 72
hours after stroke onset, HbA1C,systolic, diastolic, and mean
arterial pressure (MAP) = [(2 x diastolic)+systolic] / 3, and
CT scan findings. Patients were grouped according to age,
with Group one having age < 60 and Group two age > 65
years. On the basis of MAP patients were categorized in to
two with group one having MAP < 130mmHG and group
two>130mmHG. Hyperglycemia was defined as an
admission or in-hospital fasting blood glucose level of 126
mg/dl (7 mmol/liter) or more or a random blood glucose level
of 200 mg/dl (11.1 mmol/liter) or more on 2 or more
determinations.HBA1C were done in all patients and level
above 8.5% were taken as abnormal.9
Neuroradiological findings were determined in the
CT scan and classified according to site of SICH (basal
ganglia, thalamic, lobar), volume of haematoma (according
to ABC/2 method, in which A is the greatest diameter on the
largest haemorrhage slice, B is the diameter perpendicular to
A, and C is the approximate number of axial slices with
haemorrhage multiplied by the slice thickness),10midline
shift (the displacement of the septum pellucidum across
midline, using as reference a perpendicular line connecting
the anterior and posterior insertions of the cerebral falx at the
level of the lateral and third ventricle,11,12intraventricular
extension of haemorrhage (graded according to Graeb's
scale).12On the basis of volume of haematoma patients were
categorized into three with group one having volume < 30 ml,
group two 30-60 ml and group three>60ml. The primary end
point of the study was in-hospital mortality. The patients were
divided into 2 broad groups, good outcome groups (i.e.
patients who survived), and poor outcome group (patient who
died). All patients were given appropriate standard
therapeutic care and were monitored during the stay in
hospital (up to a maximum of 21 days). All standard
investigations such as blood sugar, lipid profile, HBA1C
were done from research laboratory of Liaquat University
Hospital Hyderabad/Jamshoro and CT scan from the
radiology department of the same institution.
Categorical variables as age, sex, volume of
haematoma, GCS score, hyperglycaemia and site of
haematoma were expressed as percentage and frequency. The
chi-square test was used for comparing categorical variables
such as hyperglycaemia, GCS score, age and volume of
haematoma with the outcome of the patients. The multiple
regression method was used to adjust the variables. A p-value
0.05 was considered as statistically significant. All calculations
Vol. 60, No. 8, August 2010661

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were done using SPSS version 16 (Chicago, IL, USA).
Results
Of the 450 consecutive patients 399 fulfilled the
inclusion criteria. Males were 261(65.4%) and females 136
(36, 4%).Patients over 65 years age were 222(55.6%) and
177(44.4%) were less than 65 years. Stress hyperglycaemia
was present in 109 (27.3%) cases and 290(72.7%) were
normoglycaemic. Out of 109 patients, 59(54.12%) died during
the follow up period as compared to 63(21.7) of the 290
patients without hyperglycaemia (p=0.001). GCS score at the
time of admission was 3-4 in 120(30.1%) 5-12 in 203(50.9%)
and 13-15 in 76(19%) patients. Volume of haematoma was <
30 ml in 183 (45.9%), 30-60ml in194 (48.6%) and >60 in 22
(5.5%) patients. GCS score at the time of admission was 3-4
in 120 (30.1%), 5-12 in 203 (50.9%) and 13-15 in 76 (19%)
cases. Site of lesion was thalamus in 174(43.6%), putamen in
81(20.3%) and lobar in 144 (36.1%) patients. Intraventricular
extension and midline shift was present in 37(9.3%) patients.
A total of 122 (9.3%) patients died during hospitalization.
Table-1 shows the comparison of various variables
with the outcome of the patients. All the variables studied had
a significant influence on the prognosis. In multivariable
analysis only hyperglycaemia (0.001) and GCS score (0.002)
at the time of admission proved to be important predictors of
mortality Table-2.
Discussion
This study has shown that hyperglycaemia is an
important predictor of outcome of patients with intracerebral
haemorrhage. In our study hyperglycaemia was present in
27.3% cases which were higher than 17% reported by
Passero S13who studied 1085 patients with intracerebral
haemorrhage.
In our study 54.2% patients died during
hospitalization .These figures are close to that observed by
Ezzeddine et al14that admission hyperglycemia is an
independent predictor of mortality with 45% mortality as
compared to 5% in patients without hyperglycemia and
intracerebral haemorrhage. In a study of 181 patients by
Odufuye et al, the mortality was 22 times more in patients
with intracerebral haemorrhage who had hyperglycaemia at
the time of admission without a previous history of diabetes
mellitus.15This statement was further strengthened by
Demchuk et al who found hyperglycaemia without diabetes a
strong predictor of poor outcome in patients with
intracerebral haemorrhage.
In this study in addition to hyperglycaemia the other
variables influencing the outcome of patients with
intracerebral haemorrhage include haematoma volume, age
and level of consciousness at the time of admission.
The GCS score is now a standard neurological
assessment tool that is reproducible and reliable.16It has been
associated with ICH outcome in other prediction models.17
Levels between 3-4 correlated with a poor prognosis.
Likewise, patients with GCS scores of >13 tend to have a
much better outcome. According to Broderick JP, Brott T
patients in whom the haematoma volume was 60 cm or
greater and the GCS score was 8 or less, the predicted 30- day
mortality rate was 91% compared to 19% in those with a
volume less than 30 cm3and the GCS score was 9 or more.18
Size of the haemorrhage has been reported to correlate well
with acute ICH mortality.19,20Our study found a significant
correlation between size of the haematoma and ICH mortality
in agreement with Drury et al21and Kanaya et al.22According
to another study, intracerebral haemorrhage volume was
consistently associated with the outcome.23Claude Hemphill
contradicts the size of volume as a strong predictor of
outcome and stated that other predictors such as low GCS
score, advanced age, or IVH influenced outcome to a greater
degree.24
In our study more deaths were found in patients over
65 years of age. Some studies have shown age as an
independent predictor of ICH whereas others did not find this
association.24The fact that age has been an inconsistent ICH
outcome predictor among various models and may have its
strongest influence among the group of very elderly patients
suggests two possibilities. Either the very elderly sustain
662 J Pak Med Assoc
Table-1: Comparison of variables with the
outcome Of the patients (n=399).
VaraiblesDead Alive Number P=value
Hyperglycaemia absent63 227290
0.001
Hyperglycaemia present 5950109
Volume of Haematoma(ml)
<30ml23 160 183
30-60ml 85109 194 0.004
>60ml14822
GCS Score
13-15 1165 76
05-1219 184 2030.004
3-4 92 28120
Age of patients
<65 years59163 222
0.063
>65 years63 114177
Table-2: Multivariate analysis of various variables related to
outcome of the patients (n = 399).
ParameterOdds Ratio 95% CIP value
Hyperglycaemia 10.94.72 - 25.32 < 0.001*
GCS Score 14.074.59 - 43.11 0.002*
Volume of Haematoma 0.390.09 - 1.660.20
Age of the patient 1.53 0.82 - 2.830.17
* P value is statistically significant calculated by
Multivariate analysis (Logistics Regression).

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worse neurological injury from ICH irrespective of size or
location, or overall medical care decisions in elderly patients
are less aggressive even if ICH-related neurological injury is
not as profound.
In this study on multivariate analysis, hyperglycaemia
and GCS score at the time of admission have appeared as
significant independent predictors of death. In the study by
Passero et al,13high admission blood glucose was associated
with variables signifying the severity of stroke, such as initial
MAP,haematoma volume, shift of cerebral midline structures,
intraventricular extension, and disturbed consciousness.
Conclusion
Stress hyperglycemia is a common finding and is a
marker of poor outcomes and higher mortality in patients
with intracerebral haemorrhage. This is more so in patients
with no history of diabetes compared to patients with
normoglycaemia. Estimation of Blood glucose in patients
with stroke is mandatory and if hyperglycaemia is detected, it
should be treated aggressively.
Acknowledgement
We are thankful to Dr. Ghulam Hussain, incharge
neurology unit for his tremendous support. We are also
grateful to Dr. Iftikhar, Dr. Tooba and Dr. Haleema for their
help and guidance in writing this article.
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