Some types of delirium indicate approaching death

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In cancer patients nearing the end of life, certain subtypes of delirium – specifically, hypoactive and “mixed” delirium – are a strong indicator that death will come soon, reports a new study.

“Terminally ill patients with the hypoactive or mixed subtypes of delirium showed a higher probability of imminent death, with even earlier mortality among younger patients,” according to the new research by Dr Sung-Wan Kim, and colleagues of Chonnam National University Medical School Gwangju, Republic of Korea. They believe their findings might help make more accurate predictions of survival in patients nearing the end of life.

The researchers looked at the relationship between delirium and survival time in 322 patients with terminal cancer entering palliative care. Delirium refers to confusion, altered awareness, or altered thoughts. It can result from many different illnesses, medications, and other causes.

Delirium was divided into sub-types according to standard DSM-5 criteria: hyperactive delirium, with increased motor activity, loss of control, and restlessness; hypoactive delirium, with decreased activity, decreased speech, and reduced awareness. Patients with normal psychomotor activity or fluctuating activity levels were classified as having “mixed” delirium.

About 30% of patients were diagnosed with delirium on entering palliative care. Of these, the delirium subtype was hyperactive in about 15% of patients, hypoactive in 34%, and mixed in 51%.

Survival time after entering palliative care was shorter for patients with delirium: median 17 days, compared to 28 days for those without delirium. However, the difference was significant only for patients with hypoactive or mixed delirium – with median survival times of 14 and 15 days, respectively. These differences remained significant after adjustment for other factors. For patients with hyperactive delirium, survival was not different from that in patients without delirium.

While delirium was more common in older patients, the effects on time to death were actually stronger in younger patients. That was consistent with previous studies suggesting shorter survival times in younger patients diagnosed with delirium

Why are different delirium sub-types associated with differing survival times? It may have to do with differences in the underlying causes of and treatment responses. Hyperactive delirium is commonly related to reversible causes, such as medication side effects.

“In contrast, hypoactive delirium is generally related to hypoxia (decreased oxygen levels), metabolic disturbances, and multi-organ failure,” Kim explains. “Therefore, hypoactive delirium could be associated with a higher mortality rate than hyperactive delirium.”

Kim adds, “Also, the earlier mortality in younger patients overturns a conventional assumption for survival prediction of delirium. Although delirium was more prevalent in older patients, as known, the irony is that delirium predicted shorter survival in younger patients.”

Accurate predictions of survival time in terminally ill patients are important for many reasons – “in terms of ensuring good clinical decision making, developing care strategies, and preparing for the end of life in a dignified manner.” The researchers conclude, “Thus, the present findings could facilitate more precise predictions of survival, allowing families to prepare for the patient’s death.”

Objective: This study investigated the differential associations between delirium and mortality in terminally ill patients according to delirium subtype and age.
Methods: This was a prospective cohort study of terminally ill patients. Delirium was diagnosed using the confusion assessment method. Delirium subtypes were defined based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and the Delirium Rating Scale-98-R. A multivariate Cox proportional hazards regression analysis was used to examine predictors of mortality.
Results: Of the 322 cases, 98 patients (30.4%) were diagnosed as having delirium. The median (interquartile range) number of survival days after admission was 17.0 (10.0-36.0) days for patients with delirium and 28.0 (16.0-57.0) days for patients without delirium (p = .002). A multivariate analysis revealed that patients with hypoactive and mixed subtypes of delirium survived for shorter periods compared with patients without delirium (hazard ratio [HR] = 1.65 [95% confidence interval {CI} = 1.05-2.59, p = .029] and HR = 2.30 [95% CI = 1.44-3.69, p = .001], respectively). The hypoactive and mixed delirium subtypes exhibited significant interactions with age: younger age was associated with shorter periods of survival in patients with hypoactive and mixed subtype delirium (HR = 0.95 [95% CI = 0.93-0.98, p < .001] and HR = 0.97 [95% CI = 0.93-1.00, p = .038], respectively).
Conclusions: The hypoactive and mixed subtypes of delirium were associated with shorter survival periods in terminally ill patients, and these associations interacted significantly with age. These findings support the clinical and academic value of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition specifiers that differentiate the diagnoses of delirium subtypes.

Wolters Kluwer material
Psychosomatic Medicine: Journal of Behavioural Medicine abstract

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