Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase-R)

Abstract

Background Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy. Subjects, Materials, and Methods We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data‐recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2). Results Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy. Conclusion Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure. Implications for Practice Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.

Pharmacological and non-pharmacological treatment of delirium in an oncological hospital service: an integrative review

“…This integrative review found a sample of ten articles (16)(17)(18)(19)(20)(21)(22)(23)(24)(25) , which were in accordance to the inclusion criteria. All of them took place in hospitals, four of which were in the United States, three in Japan, one in Saudi Arabia, one in England, and one in Switzerland.…”

“…The data collection of the articles (16)(17)(18)(19)(20)(21)(22)(23)(24)(25) included in the integrative review was made possible by an instrument that contained: identification, characteristics of the study and evaluation of the methodological rigor (12) .…”

Are common delirium assessment tools appropriate for evaluating delirium at the end of life in cancer patients?

“…This was a secondary analysis of a registry study designed to examine the efficacy and safety of antipsychotics for advanced cancer patients with delirium. 22 The research was conducted in accordance with the principles of the Declaration of Helsinki. The ethics committee of Osaka University (approval number: 13295) and the institutional review boards at all sites approved the study protocol.…”

C‐reactive protein, delirium, and other psychological symptoms among patients with advanced cancer

“…To evaluate the relationship between CRP levels and the incidence of delirium, adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjustments for independent variables known as potential risk factors for developing delirium in cancer patients, such as age, sex, CNS metastasis, cerebrovascular disease, dementia, ECOG PS, calcium corrected with albumin, and the opioid oral morphine milligram equivalent. [18][19][20][21][22][23][24][25][26][27] We entered them into the logistic model. We sequentially introduced variables into the model, first demographic and biological variables and then dose of opioid to understand the effect of opioid as confounding factors to the effects of other factors for developing delirium in patients with advanced cancer.…”

“…17 Delirium is frequently observed in patients with advanced cancer with a prevalence of between 30% and 40% at admission to palliative care units and up to 90% at the end of life. 18,19 Delirium may be a source of distress among not only patients themselves but also their families because attention or awareness deficits impede the ability to communicate within the family and affect decision making for end-of-life care planning. 20,21 Previous studies reported that the causes of delirium are opioids, corticosteroids, psychotropic drugs, anticholinergic drugs, hypercalcaemia, hyponatremia, dehydration, hypoxia, infection, and organic damage to the CNS.…”