Clinical Question

Does adding lorazepam (Ativan) to haloperidol improve symptoms of agitation in patients with advanced cancer and acute delirium?

Bottom Line

Using a single dose of lorazepam in combination with haloperidol decreases agitation in end-of-life patients with cancer who had persistent agitated delirium despite scheduled haloperidol. A recent POEM (https://www.aafp.org/afp/2017/0315/od3.html) reported that haloperidol increases symptoms of distress in patients with cancer and acute delirium who are receiving palliative care. The findings from the current study suggest that lorazepam alone may provide relief, although this can be fully answered only with a trial that includes a benzodiazepine-only arm. Further, the patients in the current study had an average age of 65 years, so the findings may not apply to an older population. (Level of Evidence = 1b)

Synopsis

These investigators enrolled patients from an acute palliative care unit with a history of advanced cancer and a diagnosis of delirium with agitation. The Richmond Agitation-Sedation Scale (RASS) score was used to identify agitation (range: −5 to 4, where −5 = unarousable and 4 = combative). After enrollment in the study, all patients received open-label haloperidol, 2 mg intravenously every four hours, with 2 mg every hour as needed for agitation. Once patients had a RASS score of 2 or more and required a rescue medication, they received a single dose of lorazepam, 3 mg intravenously, or an identical placebo based on their randomization group, followed by 2 mg of haloperidol. All patients also received standardized care for delirium including treatment for potentially reversible causes, nonpharmacologic delirium prevention measures, and symptom management.

Patients in the two groups were similar at baseline, with a mean age of 65 years, a mean RASS score of 1.6, and a median survival of 73 hours. Out of the 90 patients who were randomized in this study, 29 patients in each group received the study medication and were included in the modified intention-to-treat population. The primary outcome was the RASS score eight hours following the study medication. The addition of lorazepam led to a greater reduction in RASS score compared with placebo (−4.1 points vs. −2.3 points; P < .001). In addition, patients in the lorazepam group required lower doses of rescue drugs and were more likely to be perceived in greater comfort by nurses and caregivers. There were no significant differences in adverse effects or overall survival.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Reference:HuiDFrisbee-HumeSWilsonAet alEffect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial. JAMA2017;318(11):1047–1056.