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(Stroke. 2008;39:512.)
© 2008 American Heart Association, Inc.

Cochrane Corner

Mannitol for Acute Stroke

Dániel Bereczki, MD, PhD, DSc; Ming Liu, MD; Gilmar Fernandes do Prado, MD, PhD István Fekete, MD, PhD

From the Department of Neurology (D.B.), Semmelweis University, Budapest, Hungary; the Department of Neurology (D.B., I.F.), Health Science and Medical Center, University of Debrecen, Hungary; the Department of Neurology (M.L.), West China Hospital, Sichuan University, China; and the Department of Internal Medicine (G.F.d.P.), Federal University of Sao Paulo, Brazil.

Correspondence to Dr Daniel Bereczki, Department of Neurology, Semmelweis University, Balassa U. 6, Budapest, Hungary, H-1083. E-mail bereczki{at}neur.sote.hu

Graeme J. Hankey MD, FRCP Section Editor:

Key Words: acute stroke • edema, brain • systematic review • treatment

	Introduction

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 
Mannitol is an osmotic agent and a free radical scavenger and thus might decrease edema and tissue damage in stroke, and has been given a Class 2a recommendation (ie, probably indicated to decrease brain edema after large cerebral infarctions) for use in acute stroke in recent guidelines.¹

	Objectives

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 
To test whether treatment with mannitol reduces short and long-term case fatality and dependency after acute ischemic stroke or intracerebral hemorrhage (ICH).

	Search Strategy

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 
We searched the Cochrane Stroke Group Trials Register, the Chinese Stroke Trials Register, the China Biological Medicine Database, MEDLINE (1966 to 2006), and the Latin-American database LILACS (1982 to December 2006). In addition we searched the database of Masters and PhD degree theses at Sao Paulo University and abstracts of medical congresses on neurology and neurosurgery from 1965 to 2006 in Brazil. We searched reference lists and contacted authors of published trials. Last searches were performed between September 2006 and February 2007.

	Selection Criteria

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 
Truly randomized unconfounded clinical trials comparing the effect of mannitol with placebo or open control in patients with acute ischemic stroke or nontraumatic intracerebral hemorrhage were eligible for inclusion.

	Data Collection and Analysis

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 
Two reviewers independently selected the trials for inclusion, extracted, and analyzed the data. Included trials were tabulated for methodological quality. Data synthesis and analysis was performed using RevMan version 4.3.1.

	Main Results

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 
Three trials fulfilled the inclusion criteria. The number of included patients was small (21, 77, and 128 patients). One trial with 77 subjects randomized patients with presumed ischemic stroke without CT verification, and the other 2 trials included patients with CT verified ICH. Data on the primary outcome measure (ie, death and dependency) were not available in any of the trials. Death and disability could be calculated in the larger trial on ICH, without differences between the mannitol and the control groups (Peto OR: 1.28, 95% CI: 0.64 to 2.56). Of the secondary outcome measures, case fatality was not reported in the single trial on ischemic stroke and data were not available from the investigators. Case fatality did not differ between the mannitol and the control groups in the 2 small trials on ICH (Peto OR: 1.03, 95% CI: 0.47 to 2.25; Figure). Clinical improvement was not more frequent after mannitol treatment in any of the trials. Adverse events were either not found or not reported in the trials. Based on these 3 small trials neither beneficial nor harmful effects of mannitol could be proved. Although no statistically significant differences were found between the mannitol treated and the control groups, the confidence intervals for the treatment effect estimates were wide and included both clinically significant benefits and clinically significant harms as possibilities.

View larger version (11K): [in this window] [in a new window]   Figure. The effect of mannitol on case fatality in intracerebral hemorrhage.

	Reviewers’ Conclusions

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 
There is currently not enough evidence to decide whether the routine use of mannitol in acute stroke would result in any beneficial or harmful effect. The routine use of mannitol in all patients with acute stroke is not supported by any evidence from randomized controlled clinical trials. Further trials are needed to confirm or refute whether the routine use of mannitol is beneficial in acute stroke. This is a brief summary of our review with the full text available in the Cochrane Library.²

	Acknowledgments

 
Disclosures

None.

Received June 15, 2007; accepted June 20, 2007.

	References

Top Introduction Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Reviewers' Conclusions References

 

1. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF; American Heart Association; American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007; 38: 1655–1711.[Abstract/Free Full Text]
2. Bereczki D, Liu M, Prado GF, Fekete I. Mannitol for acute stroke (Cochrane Review). The Cochrane Database of Systematic Reviews, 2007, Issue 3.

This article has been cited by other articles:

				E.S. Prakash Is the Use of Hypertonic Mannitol Appropriate in the Management of Intracerebral Hemorrhage? Stroke, May 1, 2008; 39(5): e85 - e85. [Full Text] [PDF]

				D. Bereczki, M. Liu, G. F. do Prado, and I. Fekete Response to Letter by Prakash Stroke, May 1, 2008; 39(5): e86 - e87. [Full Text] [PDF]

This Article Full Text (PDF) All Versions of this Article: 39/2/512    most recent STROKEAHA.107.496778v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bereczki, D. Articles by Fekete, I. Search for Related Content PubMed PubMed Citation Articles by Bereczki, D. Articles by Fekete, I. Related Collections Acute Cerebral Hemorrhage Acute Cerebral Infarction Other Stroke Treatment - Medical