Delirium is a common complication in terminally ill cancer patients. Identification of underlying pathologies and prediction of clinical features may improve effective symptom alleviation. This study aims to clarify precipitating factors and their associations with clinical features of terminal delirium. Consecutive hospice inpatients who developed delirium were prospectively evaluated following a structured protocol. Among 237 patients followed until death, 245 episodes of delirium were identified in 213 patients. Precipitating factors for delirium were disclosed in 93% of the 153 cases in which investigations were completed. Mean number of etiologies was 1.8 +/- 1.1 per patient, and two or more factors were recognized in 52%. The main pathologies identified were hepatic failure, medications, prerenal azotemia, hyperosmolality, hypoxia, disseminated intravascular coagulation, organic damage to the central nervous system, infection, and hypercalcemia. Occurrence of hyperactive delirium and the requirement for symptomatic sedation significantly correlated with hepatic failure, opioids, and steroids, while dehydration-related pathologies were significantly associated with hypoactive delirium. Complete recovery was frequently achieved in cases with medication- and hypercalcemia-induced delirium, whereas a low remission rate was related to hepatic failure, dehydration, hypoxia, and disseminated intravascular coagulation. In conclusion, standard examinations can confirm factors potentially contributing to delirium and thereby predict the severity of agitation and clinical outcomes.

The maintenance of intellectual activity is an important area in the "good death" concept. To clarify the communication capacity levels of terminally ill cancer patients in their final week, and to identify factors contributing to the development of communication capacity impairment and agitated delirium, a retrospective study was performed on 284 consecutive hospice inpatients. The data were collected by chart review, and two independent raters measured the degree of communication capacity and agitation in the last week, using multiple items from the Memorial Delirium Assessment Scale, the Communication Capacity Scale, and the Agitation Distress Scale. The percentages of patients who could achieve complex communication were 43%, 28%, and 13% at 5 days, 3 days, and 1 day before death, respectively. Agitated delirium was identified in 20%. Patients receiving opioids at a dose of > or =120 mg oral morphine equivalents/day one week before death were significantly unable to communicate clearly 3 days before death (0.48 [0.28-0.84], P=0.011). Male gender and the presence of icterus were identified as significant contributors to the development of agitated delirium (odds ratios [95% C.I.]=2.6 [1.4-5.0], P<0.01; 2.4 [1.3-4.4], P< 0.01). These findings demonstrate that communication capacity impairment and agitated delirium are frequently observed in terminally ill cancer patients, and are significantly correlated with a higher dose requirement of opioids and the presence of icterus. To explore the best management to maintain the intellectual activity of dying patients, research should focus on a homogeneous sample of patients receiving high-dose opioids and those with hepatic encephalopathy. In the meanwhile, clinicians should educate patients and family members about the nature of the dying process and help facilitate the completion of life purposes requiring complex mental activities before the latest stages of cancer.

Partial opioid substitution with fentanyl and moderate levels of hydration had no significant preventive effects on the occurrence of agitated delirium in the last week on a mass level. We should explore new strategies to prevent agitated delirium that are practically available in Japan.

No abstract

Although tolerance to midazolam is sometimes described in the palliative care literature, no studies have systemically examined the possibility. To explore the association between midazolam dose for symptom palliation and the administration period, a retrospective study was performed on 62 terminally ill cancer patients who required parenteral midazolam in the final three days of life. The mean maximum dose and administration period of midazolam were 38 +/- 45 mg/day (median = 24) and 10 +/- 19 days (median = 2.5), respectively. Thirteen patients (21%) received midazolam at a dose of 60 mg/day or more, and 13 patients (21%) received it for 14 days or longer. The maximum doses were significantly correlated with patient age (rho = -0.32, P = 0.012) and the administration period (rho = 0.47, P < 0.01); and were significantly higher in patients who received midazolam for 14 days or longer (74 +/- 63 mg/day vs. 28 +/- 34 mg/day, P < 0.01). Multivariate analyses revealed that younger age (< or =70) and longer administration periods (> or =14 days) were independent determinants for a midazolam requirement of 60 mg/day or more (odds ratios [95% C.I.] = 0.091 [0.009 - 0.92], P = 0.042; 11 [2.3 - 54], P < 0.01; respectively). The significant correlation of midazolam doses with administration period suggests that the longer use of midazolam can result in the development of tolerance. This finding suggests that midazolam should be reserved for patients with limited prognoses.