IMPORTANCE Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care.OBJECTIVE To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care. DESIGN, SETTING, AND PARTICIPANTSA double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more.INTERVENTIONS Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. MAIN OUTCOME AND MEASURESImprovement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival.RESULTS Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both active arms had more extrapyramidal effects (risperidone, 0.73; 95% CI, 0.09-1.37; P = .03; and haloperidol, 0.79; 95% CI, 0.17-1.41; P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50; P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95% CI, 0.91-1.84; P = .14). CONCLUSIONS AND RELEVANCEIn patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added.

The findings demonstrate both the need for more frequent and/or earlier referral of dying patients and the need for generalist staff to become more skilled in the delivery of palliative care. It also highlights the need for palliative care clinicians to be educators and advocates within services to enhance care at end-of-life.

The unaddressed palliative care needs of patients with advanced, nonmalignant, lung disease highlight the urgent requirement for new models of care. This study describes a new integrated respiratory and palliative care service and examines outcomes from this service.The Advanced Lung Disease Service (ALDS) is a long-term, multidisciplinary, integrated service. In this single-group cohort study, demographic and prospective outcome data were collected over 4 years, with retrospective evaluation of unscheduled healthcare usage.Of 171 patients included, 97 (56.7%) were male with mean age 75.9 years and 142 (83.0%) had chronic obstructive pulmonary disease. ALDS patients had severely reduced pulmonary function (median (interquartile range (IQR)) forced expiratory volume in 1 s 0.8 (0.6–1.1) L and diffusing capacity of the lung for carbon monoxide 37.5 (29.0–48.0) % pred) and severe breathlessness. All patients received nonpharmacological breathlessness management education and 74 (43.3%) were prescribed morphine for breathlessness (median dose 9 mg·day−1). There was a 52.4% reduction in the mean number of emergency department respiratory presentations in the year after ALDS care commenced (p=0.007). 145 patients (84.8%) discussed and/or completed an advance care plan. 61 patients died, of whom only 15 (24.6%) died in an acute hospital bed.While this was a single-group cohort study, integrated respiratory and palliative care was associated with improved end-of-life care and reduced unscheduled healthcare usage.

Early and routine involvement of palliative care in patients with incurable lung cancer is acceptable to the majority of treating clinicians. To facilitate early integration of palliative care, palliative care providers need to become front-line team members who provide a high-quality service. Lung cancer clinicians need further education as to the role and benefits of early palliative care, and how best to introduce this.

Despite calls for integrated palliative care, this occurs late or not at all for many patients with cancer. Our findings demonstrate the application of targeted cancer-specific transition points to trigger integration of palliative care as a standard part of quality oncological care and augment clinician-based referral in routine clinical practice.