Methods
This was a retrospective case-control study of patients who died in the Edward Hines Jr. Veterans Affairs Hospital CLC in Hines, Illinois, under the treating specialty nursing home hospice from October 1, 2013 to September 30, 2015. Due to the retrospective nature of this trial, the use of antipsychotics within the last 2 weeks of life was a surrogate marker for development of terminal delirium. Cases were defined as patients who were treated with antipsychotics for terminal delirium within the last 2 weeks of their lives. Controls were defined as patients who were not treated with antipsychotics for terminal delirium within the last 2 weeks of their lives. Living hospice patients and patients who were discharged from the CLC before death were excluded.
The goals of this study were to (1) determine risk factors in the VA CLC hospice veteran population for the development of terminal delirium; (2) evaluate documentation by the nursing staff of nonpharmacologic interventions and indications for antipsychotic use in the treatment of terminal delirium; and (3) examine the current usage patterns of antipsychotics for the treatment of terminal delirium.
Veterans’ medical records were reviewed from 2 weeks before death until the recorded death date. Factors that were assessed included age, war era of service, date of death, terminal diagnosis, time interval from cancer diagnosis to death, comorbid conditions, prescribed antipsychotic medications, and other medications potentially contributing to delirium. Nursing documentation was reviewed for indications for administration of antipsychotic medications and nonpharmacologic interventions used to mitigate the symptoms of terminal delirium.
Statistical analysis was conducted in SAS Version 9.3. Cases were compared with controls using univariate and multivariate statistics as appropriate. Comparisons for continuous variables (eg, age) were conducted with Student t tests. Categorical variables (eg, PTSD diagnosis) were compared using χ2 analysis or Fisher exact test as appropriate. Variables with a P value < .1 in the univariate analysis were included in logistic regression models. Independent variables were removed from the models, using a backward selection process. Interaction terms were tested based on significance and clinical relevance. A P value < .05 was considered statistically significant.
Results
From October 1, 2013 to September 30, 2015, 307 patients were analyzed for inclusion in this study. Within this population, 186 received antipsychotic medications for the treatment of terminal delirium (cases), while 90 did not receive antipsychotics (controls). Of the 31 excluded patients, 13 were discharged to receive home hospice care, 11 were discharged to community nursing homes, 5 died in acute care units of Edward Hines, Jr. VA Hospital, and 2 died outside of the study period.
The mean age of all included patients was 75.5 years, and the most common terminal diagnosis was cancer, which occurred in 156 patients (56.5%) (Table 1). The baseline characteristics were similar between the cases and controls, including war era of veteran, terminal diagnosis, and comorbid conditions. The mean time between cancer diagnosis and death was not notably longer in the control group compared with that of the case group (25 vs 16 mo, respectively). There was no statistically significant difference in terminal diagnoses between cases and controls. Veterans in the control group spent more days (mean [SD]) in the hospice unit compared with veterans who experienced terminal delirium (48.5 [168.4] vs 28.2 [46.9]; P = .01). Patients with suspected infections were more likely found in the control group (P = .04; odds ratio [OR] = 1.70; 95% CI, 1.02-2.82).
The most common antipsychotic administered in the last 14 days of life was haloperidol. In the case group, 175 (94%) received haloperidol at least once in the last 2 weeks of life. Four (4.4%) veterans in the control group received haloperidol for the indication of nausea/vomiting; not terminal delirium. Atypical antipsychotics were infrequently used and included risperidone, olanzapine, quetiapine, and aripiprazole.
A total of 186 veterans received at least 1 dose of an antipsychotic for terminal delirium: 97 (52.2% ) veterans requiring antipsychotics for the treatment of terminal delirium required both scheduled and as-needed doses; 75 (40.3%) received only as-needed doses, and 14 (7.5%) required only scheduled doses. When the number of as-needed and scheduled doses were combined, each veteran received a mean 14.9 doses. However, for those veterans with antipsychotics ordered only as needed, a mean 5.8 doses were received per patient. Administration of antipsychotic doses was split evenly among the 3 nursing shifts (day-evening-night) with about 30% of doses administered on each shift.
Nurses were expected to document nonpharmacologic interventions that preceded the administration of each antipsychotic dose. Of the 1,028 doses administered to the 186 veterans who received at least 1 dose of an antipsychotic for terminal delirium, most of the doses (99.4%) had inadequate documentation based on current long-term care guidelines for prudent antipsychotic use.9
Several risk factors for terminal delirium were identified in this veteran population. Veterans with a history of drug or alcohol abuse were found to be at a significantly higher risk for terminal delirium (P = .04; OR, 1.87; 95% CI, 1.03-3.37). As noted in previous studies, steroid use (P = .01; OR, 2.57; 95% CI, 1.26-5.22); opioids (P = .007; OR, 5.94; 95% CI, 1.54-22.99), and anticholinergic medications (P = .01; OR, 2.06; 95% CI, 1.21-3.52) also increased the risk of delirium (Table 2).
When risk factors were combined, interaction terms were identified (Table 3). Those patients found to be at a higher risk of terminal delirium included Vietnam-era veterans with liver disease (P = .04; OR, 1.21; 95% CI, 1.01-1.45) and veterans with a history of drug or alcohol abuse plus comorbid liver disease (P = .03; OR, 1.26; 95% CI, 1.02-1.56). In a stratified analysis in veterans with a terminal diagnosis of cancer, those with a mental health condition (eg, PTSD, bipolar disorder, or schizophrenia) (P = .048; OR, 2.73; 95% CI, 0.98-7.58) also had higher risk of delirium, though not statistically significant. Within the cancer cohort, veterans with liver disease and a history of drug/alcohol abuse had increased risk of delirium (P = .01; OR, 1.43; 95% CI, 1.07-1.91).