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Thu Jan 4 11:35:27 GMT 2007

Dear all,

Prof Ian Roberts, who chairs the Cochrane Injuries Group, has asked me
to pass on the information below, which has led to the withdrawal of the
Cochrane review on high dose mannitol. Details are available on the
CRASH2 website.
My interpretation is that this is a sad story and that we will probably
never know the truth. However it does seem that the data in the three
published papers cannot be verified, greatly reducing the body of
evidence for high dose mannitol therapy.

Tim. Coats.
Professor of Emergency Medicine.
Leicester University

Dear Tim 
The Cochrane Injuries Group conducted an investigation into some head
injury trials by Cruz et al - the details should be of interest to the
trauma community. 
We have put the key correspondence on the trial website to make it
available to our collaborators but I wondered if you could let the folk
at trauma.org know about it as well. 
Between 2001 and 2004, three reports were published by Dr Julio Cruz and
colleagues presenting the results of three clinical trials comparing
high dose and conventional dose mannitol in the treatment of head
injury. They appeared to show that high dose mannitol was dramatically
effective in reducing death and disability after head injury. 
Cruz C, Minoja G, Okuchi K. Improving clinical outcomes from acute
subdural hematomas with emergency preoperative administration of high
doses of mannitol: a randomized trial. Neurosurgery 2001;49(4):864-71.
Cruz C, Minoja G, Okuchi K. Major clinical and physiological benefits of
early high doses of mannitol for intraparenchymal temporal lobe
hemorrhages with abnormal pupilary widening. Neurosurgery
2002;51(3):628-38.
Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose
mannitol treatment in patients with Glasgow Coma Scores of 3 and
bilateral abnormal pupillary widening: a randomized trial. Journal of
Neurosurgery 2004;100(3):376-83.
The trials were included in a systematic review of the effectiveness of
mannitol in head injury and published in the Cochrane Library in July
2005. The review concluded that "high dose mannitol appears to be
preferable to conventional dose mannitol in the acute management of
comatose patients with severe head injury." 
The Cochrane Injuries Group later discovered that there were concerns
about these trials and an investigation was made the results of which
are available on the CRASH-2 website (www.crash2.lshtm.ac.uk
</exchweb/bin/redir.asp?URL=http://www.crash2.lshtm.ac.uk> ). We know
that mannitol is widely used in the management of patients with head
trauma and felt that you should be made aware of the Injuries Group
investigation as soon as possible. Please pass this message on to your
colleagues in trauma care. 
Ian 

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