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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 52, Num. 2, 2004, pp. 191-193

Neurology India, Vol. 52, No. 2, April-June, 2004, pp. 191-193

Original Article

Prescribing pattern of antiedema therapy in stroke by neurologists and general physicians

Department of Neurology, Sanjay Gandhi PGIMS, Lucknow

Correspondence Address:Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow - 226014
jkalita@sgpgi.ac.in

Code Number: ni04058

Abstract

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.

Keywords: 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],[2],[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 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 edema[1],[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 stroke[9] 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


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 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 two-third 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 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 review[7] 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 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 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.

References

1.Norris JW. Steroid therapy in acute cerebral infarction. Arch Neurol 1976;33:69-71.  Back to cited text no. 1  [PUBMED]  
2.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.  Back to cited text no. 2  [PUBMED]  
3.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.  Back to cited text no. 3  [PUBMED]  
4.Norris JW, Hachinski VC. Megadose steroid therapy in ischaemic stroke. Stroke 1985;16:150.  Back to cited text no. 4    
5.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.  Back to cited text no. 5  [PUBMED]  
6.Anderson DC, Cranford RE. Corticosteroids in ischaemic stroke. Stroke 1979;10:623-8.  Back to cited text no. 6    
7.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.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.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.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.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.   Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Hungarian Stroke Society. Consensus for the treatment of cerebrovascular disorders: Prevention, diagnostics, acute treatment, early rehabilitation. Agyerbetegregek 1996;2:3-13.  Back to cited text no. 10    
11.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.  Back to cited text no. 11  [PUBMED]  
12.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.  Back to cited text no. 12  [PUBMED]  
13.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.   Back to cited text no. 13  [PUBMED]  
14.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.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]

Copyright 2004 - Neurology India


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