Original Article

Prescribing pattern of antiedema therapy in stroke by

neurologists and general physicians
J. Kalita, U. K. Misra, P. Ranjan
Department of Neurology, Sanjay Gandhi PGIMS, Lucknow, India.

Background: In acute stroke, a number of drugs are used

to reduce the raised intracranial pressure (ICP) although their
scientific basis has not been established or shown in
randomized controlled trials. Aims: In this communication,
we report the pattern of use of antiedema therapy in acute
stroke by general physicians (GPs) and neurophysicians
(NPs) in India. Material and Methods: A questionnaire was
developed regarding the use of various antiedema measures in stroke and responses were collected either through
post or when the responders were attending a national conference. The use of antiedema therapy by NPs and GPs
was analyzed employing the Chi-square test. Results: We
could collect responses from 102 physicians, of whom 48
were NPs and 54 GPs. More than two-thirds of the physicians managed more than three strokes per week and all
used antiedema therapy at some time or the other. Thirteen
used it in all the patients and the remaining used it in patients with large and moderate strokes or in patients with
herniation. Twelve used only one drug, while the remaining
physicians used various combinations in different doses and
frequency. The prescribing pattern was significantly different between GPs and NPs with respect to the frequency of
the antiedema drugs used, type of stroke where these were
used, combination of drugs, timing and dose of mannitol.
Conclusion: This study highlights that antiedema therapy
in acute stroke is practiced without any uniformity.

edema.5 The degree of the increase in ICP depends on the size

of infarct or the hematoma, associated edema, and brain compliance. Osmotic agents (glycerol, mannitol), diuretics and
corticosteroids are often used to reduce raised ICP although
the majority of these agents are found ineffective in reducing
brain edema1,4,6 and their efficacy has not been proved by a
randomized controlled trial.7 The American Heart Association
recommended mannitol in their guidelines for the management
of spontaneous intracerebral hemorrhage (ICH) with type B
ICP waves, progressively increasing ICP and clinical deterioration due to mass effect.8 Mannitol is widely used in acute
stroke throughout the world. About 70% physicians in China
use mannitol or glycerol in acute stroke9 and mannitol is routinely used in acute stroke in several European countries as
well. Mannitol is listed amongst the recommended therapeutic
interventions by the consensus statement of the Hungarian
Stroke Society for cases with raised ICP.10 In spite of this wide
acceptance, it is not presently clear whether the routine use of
mannitol results in increased survival and decreased dependency in stroke patients.11 In India, there is no consensus guideline about the antiedema therapy in acute stroke. In this communication, we report the practice pattern of antiedema therapy
by the GPs and NPs in India based on a questionnaire.

Material and Methods

Key Words: Stroke, infarction, mannitol, glycerol, steroid

Introduction
Stroke is the third leading cause of death and mortality is
mainly due to raised intracranial pressure (ICP) and its consequences in the acute stage.1-3 Various medical and surgical measures have been evolved to treat the raised ICP.3,4 The raised
ICP in ischaemic stroke is due to vasogenic edema and in
hemorrhage due to mass effect and surrounding vasogenic

This study was conducted to evaluate the differences in the pattern of practice of antiedema therapy in acute stroke by the general
physicians (GPs) and neurophysicians (NPs) in India. The
neurophysicians were randomly selected from the directory of the
Neurological Society of India and the Indian Academy of Neurology.
The physicians were selected from the directory of the Association of
Physicians of India. These specialists were working in medical institutes, medical colleges or specialized medical centers representing
the tertiary and secondary level of medical care. Family physicians,
general practitioners and primary health care doctors were not included. A questionnaire was prepared (Table 1) and was posted to
about 100 neurophysicians of whom 48 responded. The responses
were collected from general physicians during a scientific conference

J. Kalita
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow - 226014, India. E-mail:
jkalita@sgpgi.ac.in

Neurology India June 2004 Vol 52 Issue 2

191
CMYK 191

Kalita J, et al: Prescribing pattern of antiedema therapy

Table 1: Questionnaire for the evaluation of antiedema therapy

in acute stroke
Please tick (>) all the appropriate responses.
1. How many patients with acute stroke do you see every week:
(a) 1-3
(b) 4-6
(c) More than 6
2. In patients with acute stroke how often do you use antiedema
agents:
(a) Always
(b) Sometimes
(c) Never
3. In which type of stroke do you use antiedema agents:
(a) Hemorrhage
(b) Infarction
(c) Cortical venous thrombosis
4. In your opinion antiedema agents should be used in:
(a) All patients
(b) Patients with clinical signs of brain herniation
(c) Patients with large stroke only
(d) Patients with moderate and large stroke
5. Do you use antiedema agents in combination Yes/No
(a) Mannitol + Glycerol
(b) Mannitol + Corticosteroid
(c) Glycerol + Corticosteroid
(d) Mannitol + Frusemide
(e) Any other
6. Which antiedema agents do you prefer and in what dose:
(a) Mannitol-50 ml/100ml- 4 hrly/6 hrly/8 hrly/SOS
(b) Glycerol(i) IV-500 ml-4 hrly/6 hrly/8 hrly/SOS
(ii) Oral 15 ml/ 20 ml/ 30 ml/- 4 hrly/6 hrly/8 hrly/SOS
(c) Corticosteroid- 4 mg/ 8 mg - 4 hrly/6 hrly/8 hrly/SOS
(d) Frusemide-20 mg/ 40 mg/ 80 mg- 4 hrly/6 hrly/8 hrly/SOS
7. When do you think that these agents are most useful
(a) Started within 48 hours
(b) Started within 2-5 days
(c) Started within 5-7 days
(d) Even later
Any other comment that you will like to make

by personal interview according to the fixed questionnaire. The responses to the questionnaire were tabulated and the frequency and
pattern of various antiedema therapies by NPs and GPs in acute
stroke was analyzed and was compared employing the chi square
test.

Results
We could collect responses to the questionnaire from 102; of
whom 48 were neurophysicians and 54 general physicians. Both
GPs and NPs managed patients with acute stroke. About twothird GPs and NPs managed more than 3 cases of strokes per
week. Both NPs and GPs used various drugs to reduce raised
ICP; 27 always and 75 sometimes. Most of the NPs used
antiedema drugs in hemorrhagic stroke (44) and cortical venous thrombosis (33) whereas GPs used them more frequently
in hemorrhagic strokes (44) and infarctions (35). Only 8 GPs
used antiedema therapy in cortical venous thrombosis. Thirteen physicians (8 GPs and 5 NPs) treated all the strokes with
antiedema therapy; 47 (16 GPs and 31 NPs) used these drugs

192
192 CMYK

on patients with herniation and 37 (17 GPs and 20 NPs) on

patients with large and medium-sized hematoma. Combinations
of two drugs were used by the majority of treating physicians
rather than using a single drug; mannitol and corticosteroids
by 40 (30 GPs, 10 NPs), oral glycerol and corticosteroids by 4
(1 GP, 3 NPs) and mannitol and frusemide by 39 (11 GPs, 28
NPs). These drugs were used by the majority within 24 hours
(49 GPs, 31 NPs), some within 2-5 days (4 GPs, 15 NPs) and
only 9 used them even after 5 days (1 each) of stroke. The
majority of GPs and NPs used 100 ml 20% intravenous mannitol 4-8 hourly, 30 ml oral glycerol 6-8 hourly, dexamethasone
4 mg 6-8 hourly and intravenous frusemide 40 mg 4-8 hourly.
There was an option to mention any other antiedema drugs
being used; however, none mentioned the use of hypertonic saline.
Comparing the practicing pattern of antiedema therapy by
GPs and NPs, significant differences were noted in how often
antiedema therapy was used (X2=5.40, df=1, P=0.02), type
of stroke for which it was used (X2=13.38, df=2, P=0.0001),
combinations of antiedema therapy (X2=14.98, df=4,
P=0.0001), when it was most effective (X2=11.10, df=3,
P=0.01) and dose of mannitol (X2=7.36, df=2, P<0.05). The
other parameters were not significantly different between the
NPs and GPs. The details are given in Table 2.

Discussion
In this study comprising GPs and NPs, 26% used antiedema
drugs in all the patients with stroke and the remaining sometimes. The prescribing pattern of antiedema therapy was significantly different between the two groups with respect to frequency of use, type of strokes, perception regarding the best
timing of antiedema therapy, combination of drugs and the dose
of mannitol. The use of antiedema in stroke by the NPs seems
to be more rational as compared to the GPs as they used these
drugs more often in the patients with hemorrhagic stroke (44),
patients with herniation (31) and with a more appropriate dose
and frequency of mannitol. The general physicians used
antiedema mostly in hemorrhagic strokes and infarction but
less frequently with cortical venous thrombosis. Lesser use of
antiedema in these patients by GPs may be due to the lack of
awareness about cortical venous thrombosis or the lack of widespread venography facilities. No study demonstrated the beneficial effect of corticosteroids in ischaemic strokes.1,4,6 In ICH
also dexamethasone and glycerol showed no beneficial effect.2,3
Although mannitol has been used since the last 30 years in
ICH, there is no randomized controlled trial showing its beneficial effect. Reviewing the literature on mannitol in stroke, the
Cochrane review7 has shown that 34% in the control and 33%
in the mannitol group improved whereas patients who worsened were 44% in each group. Neither harmful nor beneficial
effects of mannitol could be found. Case fatality, proportion of

Neurology India June 2004 Vol 52 Issue 2

Kalita J, et al: Prescribing pattern of antiedema therapy

Table 2: Response to the questionnaire by general physicians

and neurophysicians in the management of cerebral edema in
stroke
General

Neurologist

physician (54)
No of patients/week
1-3
19
4-6
24
>6
11
How often antiedema used
Always
19
Sometimes
35
Never
0
In which type of stroke
Hemorrhage
44
Infarction
35
CVT
8
In whom it should be used
All patients
8
Pts with herniation
16
Large stroke
17
Moderate or large stroke
17
Combinations
Mannitol + Glycerol
12
Mannitol + Corticosteroid 30
Glycerol + Corticosteroid 1
Mannitol + Frusemide
11
One only
4
When most effective
Within 48 hrs
49
2-5 days
4
5-7 days
0
Even later
1
Doses
Mannitol
100 ml 4 hrly/6 hrly/8 hrly 2/27/17
50 ml 4 hrly/8 hrly
2/1
500 ml 6 hrly
1
Glycerol
30 ml 4 hrly/6 hrly/8 hrly 0/5/3
20 ml 6 hrly
3
Cortocosteroids
4 mg 4 hrly/6 hrly
10/10
8 mg 6 hrly/8 hrly
2/5
Frusemide
40 mg 4 hrly/6 hrly/8 hrly 1/5/2
20 mg 6 hrly/8 hrly
3/0
CVT-cortical venous thrombosis

X2

P value

(48)
1.61

NS

5.40

0.02

13.38

0.0001

1.15

NS

14.98

0.0001

14
19
15
8
40
0
44
31
33
5
31
20
15
22
10
3
28
8

References
1.
2.

11.10

0.01

31
15
1
1

3.

4.

7.36

0.03

0.04

NS

0.004

NS

2.14

NS

0/17/16
9/2
0

5.

6.

3/5/7
5
3/4/4
3/0
0/8/6
0/6

dependent patients at the end of follow-up and side-effects were

not reported and were not available from investigators.12 Therefore, the routine use of mannitol in all the patients with acute
stroke is not supported by any evidence from existing randomized
clinical trials. Videen et al studied the effect of mannitol in six
patients with acute middle cerebral arterial stroke and CT evidences of midline shift. The total brain volume after 50 to 55
minutes of mannitol significantly decreased but the non-infarcted hemisphere shrank more compared to the infarcted hemisphere.13 Glycerol and corticosteroids were found ineffective to
reduce ICP in stroke, and mannitol is yet to show its efficacy in
a randomized clinical trial. In spite of these uncertainties and

Neurology India June 2004 Vol 52 Issue 2

controversies, mannitol has been recommended by the American Heart Association in their guidelines for the management
of ICH.8 The effect of glycerol in six large hemispheric infarctions
was evaluated employing the MRI technique. The ventricular
volume significantly increased and the T2 signal intensity of
the infarcted area decreased following 300 ml glycerol whereas
there was no change in the non-infarcted hemisphere.14 This
study, however, lacks clinical correlation. The indiscriminate
use of antiedema drugs and their combinations in the treatment of stroke patients unnecessarily raises the therapeutic
cost without benefit.
Our survey of the prescribing pattern of antiedema therapy
in stroke highlights the diversity and uncertainty in the field of
antiedema therapy in stroke amongst the GPs and NPs in India. More and more updates and continued medical education
programs on this topic may result in more rationalized
antiedema therapy in the management of acute stroke.

7.

8.

9.

10.

11.

12.

13.

14.

Norris JW. Steroid therapy in acute cerebral infarction. Arch Neurol

1976;33:69-71.
Poungvarin N, Bhoopat W, Viriyavejakul A, Rodprasert P, Buranasiri P,
Sukondhabhant S, et al. Effect of dexamethasone in primary supratentorial
intracerebral haemorrhage. N Engl J Med 1987;316:1229-33.
Yu YL, Kumana CR, Lauder IJ, Cheung YK, Chan FL, Kou M, et al. Treatment of acute cerebral haemorrhage with intravenous glycerol: A double blind
placebo-controlled randomized trial. Stroke 1992;23:967-71.
Norris JW, Hachinski VC. Megadose steroid therapy in ischaemic stroke. Stroke
1985;16:150.
Ebisu T, Tanaka C, Umeda M, Kitamura M, Fukunaga M, Aoki I, et al.
Haemorrhagic and non haemorrhagic stroke diagnosis with diffusion weighted
and T2 weighted echo plannar MR imaging. Radiology 1997;203:823-8.
Anderson DC, Cranford RE. Corticosteroids in ischaemic stroke. Stroke
1979;10:623-8.
Bereczki D, Liu M, Prado GF, Fekete I. Cochrane report: A systemic review of
mannitol therapy for acute ischaemic stroke and cerebral parenchymal haemorrhage. Stroke 2000;31:2719-22.
Broderick JP, Adams HP Jr, Barsan W, Feinberg W, Feldmann E, Grotta J, et
al. Guidelines for the management of spontaneous intracerebral haemorrhage
a statement for health care professional from a special writing group of stroke
council. American Heart Association. Stroke 1999;30:905-15.
Chen ZM, Sandercock P, Pan HC, Counsell C, Collins R, Liu LS, et al. Indications for early aspirin use in acute ischemic stroke: A combined analysis of
40000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke
2000;31:1240-9.
Hungarian Stroke Society. Consensus for the treatment of cerebrovascular disorders: Prevention, diagnostics, acute treatment, early rehabilitation.
Agyerbetegregek 1996;2:3-13.
Famularo G. The puzzle of neuronal death and life: Is mannitol the right drug
for the treatment of brain oedema associated with ischaemic stroke. Eur J
Emerg Med 1999;6:363-8.
Santambrogio S, Martinotti R, Sardella F, Porro F, Randazzo A. Is there a real
treatment for stroke? Clinical and statistical comparison of different treatment
in 300 patients. Stroke 1978;9:130-2.
Videen TO, Zazulia AR, Manno EM, Derdeyn CP, Adams RE, Diringer MN, et
al. Mannitol bolus preferentially shrinks non infracted brain in patients with
ischaemic stroke. Neurology 2001;57:2120-2.
Sakamaki M, Igarashi H, Nishiyama Y, Hagiwara H, Ando J, Chishiki T, et al.
Effect of glycerol on ischemic cerebral oedema assessed by magnetic resonance
imaging. J Neurol Sci 2003;209:69-74.

Accepted on 20.11.2003.

193
CMYK 193