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

Using a single dose of lorazepam in combination with haloperidol decreases agitation in end-of-life cancer patients with persistent agitated delirium despite scheduled haloperidol. A Antipsychotics worsen symptoms in patients with delirium who receive palliative care reported that haloperidol increases symptoms of distress in acutely delirious cancer patients who are receiving palliative care. The findings from the current study suggest that lorazepam alone may provide relief, though this can only be fully answered 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. (LOE = 1b)

Hui D, Frisbee-Hume S, Wilson A, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care. JAMA 2017;318(11):1047-1056.  [PMID:28975307]

Randomized controlled trial (double-blinded)

Government

Concealed

Inpatient (ward only)

These investigators enrolled patients from an acute palliative care unit with 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 4 hours along 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 either 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 2 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 8 hours following the study medication. The addition of lorazepam led to a greater reduction in RASS score as 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 perceived to be in greater comfort by both nurses and caregivers. There were no significant differences in adverse effects or overall survival.