medwireNews: Lorazepam significantly reduces the intensity of agitation, compared with placebo, in advanced cancer patients with agitated delirium despite already receiving scheduled haloperidol, US study data show.
The patients, who were all hospitalized at an acute palliative care unit, were randomly assigned to receive either intravenous lorazepam 3 mg (n=29) or placebo (n=29) in addition to intravenous haloperidol 2 mg at the onset of an agitation episode.
As reported in JAMA, participants who received lorazepam plus haloperidol had a mean 4.1-point reduction in the 10-point Richmond Agitation Sedation Scale (RASS) at 8 hours postadministration, which was significantly greater than the mean 2.3-point reduction observed among those who received placebo plus haloperidol.
In addition, the proportion of patients who developed a RASS score of 1 or more, where 1 equals restless and 4 represents a combative state, anytime during the first 8 hours was significantly lower in the lorazepam plus haloperidol group than in the placebo plus haloperidol group, at 28% versus 76%.
However, the researchers point out that, after an initial sharp fall within the first 30 minutes, the mean RASS score was between 0 (alert and calm) and –1 (drowsy) in the placebo plus haloperidol group, but was between −2 (light sedation) and –3 (moderate sedation) in the lorazepam plus haloperidol group.
This suggests that there is “a trade-off between more-effective treatment of agitation and higher levels of sedation,” they remark.
Nevertheless, patients who received lorazepam were perceived to be significantly more comfortable by caregivers (84 vs 37%) and nurses (77 vs 30%) than those who did not receive it, which they say indicates that lack of agitation was valued more greatly than the risk for excessive sedation.
Patients who received lorazepam also required significantly lower doses of rescue neuroleptics than those who did not (median 2 vs 4 mg per day) but there were no significant between-group differences in delirium-related distress or survival.
“Taken together, this study supports the judicious use of single-dose lorazepam [plus] haloperidol for patients with persistent agitated delirium after a trial of scheduled haloperidol,” David Hui (University of Texas MD Anderson Cancer Center, Houston) and co-authors conclude.
But they stress that “[t]he use of lorazepam in other combinations, populations, and indications needs to be thoroughly investigated in future clinical studies.”
In an accompanying editorial, Pratik Pandharipande and Wesley Ely, both from Vanderbilt University School of Medicine in Nashville, Tennessee, USA, say the study “provides critical evidence to help guide management of patients with hyperactive delirium in the last few days of life, a very difficult population to study.”
In spite of this, they question whether patients with hyperactive delirium should immediately receive “pharmacological restraint in the form of an antipsychotic, sedative, or anxiolytic,” suggesting that management of infections and dehydration, and supportive strategies, such as having family present, can result in less distressing delirium episodes.
“If hyperactive delirium persists after these important initial care steps, psychoactive medications remain a consideration”, Pandharipande and Ely conclude.
“The decision to use such powerful medications should be individualized for the patient using the lowest-possible doses of targeted antipsychotic medications or benzodiazepines rather than a one-size-fits-all protocol.”
By Laura Cowen
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