Feature Research ethics

Doubts over head injury studies

BMJ 2007; 334 doi: http://dx.doi.org/10.1136/bmj.39118.480023.BE (Published 22 February 2007) Cite this as: BMJ 2007;334:392
  1. Ian Roberts, clinical coordinator CRASH-2 trial,
  2. Richard Smith, visiting professor,
  3. Stephen Evans, professor of pharmacoepidemiology
  1. London School of Hygiene and Tropical Medicine, London WC1E 7HT
  1. Correspondence to: I Roberts Ian.Roberts{at}Lshtm.ac.uk

    Patients are receiving treatment that may be unsound as investigations by Ian Roberts and colleagues raise questions about whether influential trials of high dose mannitol ever took place

    Each year, worldwide, many thousands of people are treated in emergency departments for head injuries. Mannitol is an osmotic diuretic that is believed to reduce intracranial pressure after head injury and may improve patient outcome. Between 2001 and 2004, a Brazilian neurosurgeon Julio Cruz and colleagues published three clinical trials comparing high dose and conventional dose mannitol in the treatment of head injury (table).123 No other trials had examined this question.

    The results showed that high dose mannitol greatly reduced death and disability six months after the head injury. A Cochrane systematic review that included these trials concluded: “high dose mannitol seems to be preferable to conventional dose mannitol in the acute management of comatose patients with severe head injury.”4 However, one of the trials was accompanied by an editorial that questioned the reliability and validity of the results, calling for further multicentre studies.5 A subsequent investigation by the Cochrane Collaboration was unable to confirm that the studies took place.

    View this table:

     Details of trials of high dose mannitol

    Doubts over the data

    In May 2006, Dr Jorge Mejia, the Colombian national coordinator of the CRASH-2 (clinical randomisation of an antifibrinolytic in significant haemorrhage; www.crash2.Lshtm.ac.uk) trial, wrote to IR (who is editor of the Cochrane Injuries Group) after attending a meeting of the Latin American Brain Injury Consortium in Brazil. He was concerned about the inclusion of the Cruz trials in the Cochrane review:

    “During the discussion some Brazilian physicians expressed some surprise with the inclusion of Julio Cruz' paper in the meta-analysis (Cruz 2004; J Neurosurgery, 100:376) … Cruz had no patients at his arrival to Brasil, back from USA …

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