Rivastigmine should not be used for delirium in critical care patients, say researchers
Rivastigmine, a cholinesterase inhibitor, is not effective in reducing delirium in critically ill patients and might increase mortality, a Dutch study has shown.
The authors of the (published online, 5 November 2010) hypothesised that the treatment would work based on previous evidence that showed cholinesterase inhibitors were effective in treating persistent delirium in older people. Rivastigmine is also approved for the treatment of Alzheimer’s disease, Parkinson’s disease dementia and Lewy-body dementia.
In the Lancet trial, patients were randomised to receive rivastigmine or placebo added to standard treatment with haloperidol. However, the trial had to be stopped early when the mortality rate among those patients assigned to active treatment was found to be three times higher than those assigned to placebo. The median duration of delirium was also longer in the rivastigmine group than in the placebo group (see Panel). Mark Borthwick, a critical care consultant pharmacist at the John Radcliffe Hospital in Oxford, pointed out that, generally, the evidence for the use of cholinergic agents has been somewhat equivocal for delirium treatment and delirium prophylaxis.
"This study provides more evidence that the cholinergic line of therapy does not work and makes the quandary on how to treat delirious patients with dementia more stark, given that the use of antipsychotics in dementia is not desirable and is actively being managed down," he said.
He believes that the increase in mortality rates in the rivastigmine arm of the study will throw the hunt for effective drug therapy back down the antipsychotic route and may bring about considerable debate on drug therapy of delirium in dementia patients.
"Controlled studies into the use of haloperidol in critically ill patients for both delirium prophylaxis and treatment are under way and eagerly awaited," he added.
Study method and findings
Adult patients diagnosed with delirium were enrolled from six intensive care units in the Netherlands, and treated over 14 months. They were randomised to either an increasing dose of rivastigmine or placebo added to standard treatment with haloperidol. The primary outcome was the duration of delirium during hospital admission. Members of the data safety and monitoring board did an interim analysis every three months.
Only 104 of the planned sample size of 440 patients were recruited to the trial (54 on rivastigmine and 50 on placebo) when the board stopped the trial because mortality in the rivastigmine group (n=12, 22 per cent) was higher than in the placebo group (n=4, 8 per cent; P=0.07). This was not statistically significant although close to being so, say the researchers.
The median duration of delirium was longer in the rivastigmine group (five days) than in the placebo group (three days, P=0.06).
Citation: The Salvadore URI: 11042507
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