Delirium is common in the last weeks of life, occurring in 26 to 44 percent of hospitalized patients with advanced cancer, and in up to 88 percent of persons with terminal illness in the last days of life.

• Delirium is part of a wide range of organic mental disorders, which includes dementia, organic mood disorder, and organic anxiety disorder. Delirium, like dementia, is marked by a general cognitive impairment, whereas in other organic mental disorders, impairment is more selective. Delirium is distinguished from dementia in that it is deemed to be potentially reversible.

This systematic review focuses on persons with delirium secondary to underlying terminal illness who are being treated in the supportive and palliative care settings.

We found little evidence in randomized controlled trials (RCTs) of persons with delirium caused by underlying terminal illness. It would be unethical to perform a placebo-controlled trial, and it should be acknowledged that undertaking any form of clinical trial in this particularly vulnerable group is difficult.

• There is consensus based on observational evidence and experience that haloperidol and other butyrophenones, such as droperidol, are effective for the management of delirium, and are widely used. However, few RCTs assessing their effects have been undertaken.

• Although benzodiazepines (especially midazolam) are used extensively in persons with delirium who are terminally ill, we found no evidence from well-conducted trials that they are beneficial.

• We also do not know whether haloperidol, barbiturates, phenothiazines, or propofol are effective in persons with delirium caused by underlying disease. All of these drugs are associated with serious adverse effects, and some, such as barbiturates, may cause confusion and agitation. We also do not know whether artificial hydration is effective in persons with delirium.

We do not know whether switching opioids is helpful in persons who have developed opioid-induced delirium.

Definition

Delirium is defined as a nonspecific, global cerebral dysfunction with concurrent disturbances of consciousness, attention, thinking, perception, memory, psychomotor behavior, emotion, and sleep-wake cycle. There is some difficulty in assessing clinical research, because the terms “delirium” and “cognitive failure” are at times used interchangeably. Cognitive failure encompasses delirium (which is common in persons with advanced disease in the last weeks of life) and dementia, and amnesic disorders (which are relatively rare in this population). This systematic review covers only persons with delirium secondary to underlying terminal illness who are being treated in the palliative care setting.

For the purpose of this review, we have used the National Institute for Health and Clinical Excellence's definition of supportive care as follows: supportive care “helps the patient and their family to cope with cancer and treatment of it—from prediagnosis, through the process of diagnosis and treatment, to cure, continuing illness or death and into bereavement. It helps the patient to maximise the benefits of treatment and to live as well as possible with the effects of the disease. It is given equal priority alongside diagnosis and treatment.” This definition was written in relation to persons with cancer, but is applicable to all persons with terminal illness.

We have used the World Health Organization's definition of palliative care as follows: “Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.” Although this definition of palliative care does not specify incurable or terminal illness, there is consensus that palliative care applies to persons approaching the end of life (i.e., a prognosis of less than one year). Thus, supportive and palliative care embrace the same priorities of maximizing quality of life; however, supportive care aims to do this in persons who may live longer, may be cured, or are in remission from their disease.

Incidence and Prevalence

Delirium is common in the last weeks of life, occurring in 26 to 44 percent of persons hospitalized with advanced cancer, and in up to 88 percent of persons with a terminal illness in the last days of life. A key difficulty in assessing the prevalence and incidence of delirium in a population with advanced disease relates to the variety of screening instruments, scales, and terminology used (cognitive failure, delirium, agitation, and restlessness).

Etiology

Delirium is part of a wide range of organic mental disorders that includes dementia, organic mood disorder, and organic anxiety disorder. Delirium, like dementia, is marked by a general cognitive impairment, whereas in other organic mental disorders, impairment is more selective. Delirium is deemed to be potentially reversible, which distinguishes it from dementia.

In a palliative care population (47 persons with terminal cancer who died in a hospital, in which there were 66 episodes of cognitive failure over three days), it was possible to attribute a cause for the delirium in less than 50 percent of persons. These causes included medication use, sepsis, brain metastasis, organ failure, hypercalcemia, and hyponatremia. The list of potential causes of delirium is extensive, but in end-stage disease it can be subdivided as follows: central nervous system causes—primary brain tumors, metastatic spread to the central nervous system; metabolic causes—organ failure (e.g., hyper-bilirubinemia, uremia), electrolyte disturbance (e.g., hyponatremia, hypercalcemia), hypoxia; treatment adverse effects—cytotoxic chemotherapy, radiotherapy (especially cranial irradiation); other drug adverse effects—corticosteroids, opioids, anticholinergics; and other causes—anemia, nutritional deficiencies (e.g., vitamin B₁₂), paraneoplastic syndrome.

Prognosis

The prognosis of terminal illness is worsened by delirium. In one systematic review, six of seven prospective studies found a significant association between decreased survival and delirium in persons with end-stage cancer.