General Management Approach to Delirium
Except for lorazepam and midazolam in selected situations, benzodiazepines are generally not recommended for the treatment of delirium. Lorazepam is a short-acting agent, and its use is largely reserved for the treatment of alcohol or benzodiazepine withdrawal. Lorazepam (0.5-1 mg orally or parenterally, every 1-2 hours) has also been used along with haloperidol in patients with delirium who are particularly sensitive to extrapyramidal side effects. Another exception is midazolam, a very short-acting benzodiazepine, which is given by continuous subcutaneous or intravenous infusion in doses ranging from 30 to 100 mg over 24 hours. Midazolam is used to achieve deep sedation, especially in a terminal hyperactive or mixed delirium when agitation is refractory to other treatments, for example, doses of haloperidol in the region of 20 mg per day. Similarly, methotrimeprazine (a very sedating neuroleptic) is also used to achieve deep sedation in doses of 6.25 to 25 mg subcutaneously or intravenously every 8 hours.
The decision to use a deep level of pharmacologically induced sedation in the treatment of agitated delirium often raises ethical concerns, fueled by the marked variability in the reported frequency (ranging from 10% to 52%) for this practice in patients dying from advanced cancer. Consistent with the goals of care, it is important that appropriate efforts are made to assess the reversibility of delirium, clarify the intent of sedation (the relief of refractory symptoms), and maintain clear communication with family members and health care team members regarding rationale and process.[2,4] (Refer to the Delirium and Sedation for Refractory Delirium and Other Intractable Symptoms section of this summary for more information.)
Sedation for Refractory Delirium and Other Intractable Symptoms
Delirium at the end of life often requires a pharmacological sedative approach. This issue cannot be considered in isolation from the ethical dilemma that it evokes. The need to sedate terminally ill patients for poorly controlled symptoms that include delirium, pain, dyspnea, and psychological effects has been reported frequently.[29,30,31,32];[33,34][Level of evidence: III] Although clinical experience suggests that good palliative care can effectively manage the symptoms of most cancer patients, patients may experience symptoms that can be termed "refractory." Although sedative drugs are a therapeutic option, the incidence of these refractory situations in advanced cancer patients is controversial. This highlights the need to distinguish between "difficult" and "refractory" symptoms. A clear understanding of the terminology describing sedation and sedative medications is necessary; however, the extent to which sedation has been used for managing agitated delirium is difficult to clarify because of inconsistent definitions and confusing terminology.[36,37] Nevertheless, agitated behavior requiring sedation that is variously described as delirium, terminal restlessness, mental anguish, and agitation is a recurring theme in the literature.