Published online before print March 20, 2008, doi: 10.1161/STROKEAHA.108.516914
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(Stroke. 2008;39:e86.)
© 2008 American Heart Association, Inc.
Letters to the Editor |
Response to Letter by Prakash
Department of Neurology, Semmelweis University, Budapest, Hungary, Department of Neurology, Health Science and Medical Center, University of Debrecen, Hungary
Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
Department of Internal Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil
Department of Neurology, Health Science and Medical Center, University of Debrecen, Hungary
Response:
In his letter regarding our systematic review on mannitol in acute stroke1 Dr Prakash expresses his astonishment that hypertonic mannitol is used at all in the treatment of patients with intracerebral hemorrhage (ICH). Despite his surprise, several articles suggest that mannitol has been used to treat this condition all over the world including India,2 China,3 Japan,4 Italy,5 Romania, Hungary,6 and the United States.7 This practice is based on several studies like that of Haass et al8 over 20 years ago, showing that the pronounced brain edema which develops during several days after an ICH could lead to an increase in intracranial pressure requiring treatment.
A bimodal time course of mass effect is typical after ICH: the first peak occurs in the first 48 hours after the onset of ICH representing the growth of the hemorrhage, and the second peak starts a few days later associated with an increase in edema.9 Hematoma enlargement occurred in 38% of patients in the first day of ICH: in 26% within the first hour, and in a further 12% between 1 to 20 hours.10 Not only the hematoma itself but the perihematomal edema also grows in the hyperacute phase of ICH—an approximately 75% increase in edema volume was described during the first 24 hours.11 Perifocal edema was shown for at least 2 to 3 weeks in several studies.9,12 In ICH early progression is related to hematoma enlargement whereas late progression is associated with the development of extensive edema.9 To date there is no data to decide whether in the first day of ICH onset mannitol is harmful due to promoting hematoma expansion or beneficial due to decreasing early edema. As the risk of hematoma expansion decreases after the second day, whereas edema progresses thereafter, the lowest risk and largest benefit of mannitol use might be achieved if treatment starts only 1 to 2 days after ICH onset. This, however, remains a hypothesis until well-designed large studies decide whether a very early or a delayed use of mannitol is justified in acute ICH. However, because mannitol is inexpensive, academic trials are extremely difficult to run unless the current regulations change, and the limited evidence does not suggest that mannitol is beneficial in ICH, we do not think that such a large trial will be organized in the near future. According to the current guidelines based on limited evidence, osmotherapy—including mannitol—after ICH has received a Class IIa, Level of Evidence B recommendation, ie, the weight of evidence or opinion is in favor of the procedure or treatment.13
Despite all the above, based on our earlier observations on over 100 patients6 and on our systematic review1 we share the concerns of Dr Prakash that mannitol might do more harm than good in acute ICH. We assume that even if we have more reliable evidence in the future against the use of mannitol, because of the lack of an evidence-based alternative treatment, the practice of osmotherapy will not change in cases when clinical signs of increasing intracranial pressure occur: "when beliefs conflict with evidence, beliefs tend to win. It seems to be against human nature to trust scientific evidence."14
Acknowledgments
Disclosures
None.
References
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