**8. Conclusion**

*Suggestions for Addressing Clinical and Non-Clinical Issues in Palliative Care*

depends on CYP2D6 functioning.

every 45–60 min) with a maximum of 2–20 mg/day.

treatment of nausea/vomiting (including the opioid-induced ones) [28]. Even if it represents the preferred drug in the treatment of delirium, its use is limited by concern for side effects. Usually, the onset of extrapyramidal disorders is dosedependent and cardiotoxicity — QTc prolongation or torsades de pointes (with a QTc > 450–500 ms immediate drug withdrawal is recommended) — generally rarely occurs for low doses [29]. However, in patients under palliative care, many factors such as the severity of the underlying disease and organ damage, comorbidities, cachexia, hypoproteinemia, advanced age, and polytherapy can increase the risk of side effects. For example, haloperidol pharmacokinetics (**Table 2**) mostly

About doses, in mild delirium with no underlying psychiatric illness haloperidol can be used at the dose of 0.5–1 mg bid, both oral or subcutaneous (0.25–0.5 mg for elderly patients). In moderate delirium, the dose can be doubled. In severe and terminal delirium the dose is 0.5–4 mg both oral or subcutaneous (possibly repeated

Among the other antipsychotics, risperidone (0.5–4 mg/day) could be useful in patients requiring high doses of haloperidol or at high risk of developing haloperidol-induced extrapyramidal or cardiac effects. Olanzapine (2.5–10 mg/day, orally or i.m.) has an efficacy comparable to haloperidol but can induce sedation due to its antihistaminergic action; thus, it is not recommended in elderly patients with dementia or hypoactive delirium, although its use can be beneficial for the regulation of the sleep–wake rhythm [30]. Quetiapine (from 12.5–25 mg/day up to an average dose of 50–175 mg/day) has an intense antihistaminergic activity which can worsen confusion. It can also cause hypotension. Finally, the first-generation antipsychotic agent levomepromazine is also used to address intractable nausea or vomiting, and for severe delirium in the last days of life. This phenothiazine is administered orally or by subcutaneous bolus injection (10–25 mg, repeatable as required after 2 hours) or continuous subcutaneous infusion (25–100 mg/day).

It must be emphasized that the efficacy of antipsychotics and other pharmacological interventions for the treatment of delirium in palliative care is still under debate [31, 32]. The use of antipsychotics and/or other medications becomes inevitable for the management of hyperactive or mixed delirium with severe agitation and anxiety but they must be given short-term and at the lowest effective dose. Symptomatic

therapy of delirium is also mandatory if it becomes a source of suffering.

*i.m*.: 20.7 hrs (decanoate i.m.: 21 days)

administration *i.v*.: 10.1–26.2 hrs

*s.c*.:10–15 min *i.v*.: seconds

*i.v*.: 4–6 hrs

Onset of action *p.o*.: > 1 hr.

Duration of action *s.c*.: up to 24 hrs

Vd 9.5–21.7 L/kg

Cl 0.9–1.5 l/kg/h

PPB 92%

*Plasma protein binding; Cl, Clearance.*

*Main haloperidol pharmacokinetics.*

T1/2 *p.o*.: after a single dose (e.g., 2–4 mg) 14.5–36.7 hrs; up to 21 days after chronic

*Abbreviations: p.o., oral; i.m., intramuscular; s.c., subcutaneous; i.v., intravenous; Vd: Volume of distribution; PPB,* 

**8**

**Table 2.**

Although clinical experience and scientific evidence underline that delirium can lead to multiple clinical and healthcare problems and that its timely recognition and treatment can induce a remission of the clinical picture, screening of cognitive conditions and delirium remains an unmet need. As the efficacy of pharmacological treatments has not yet been proven, greater efforts must be focused on prevention and early diagnosis. In short, the strategies to be adopted for prevention are quite codified. It is crucial to recognize potential risk factors and, since according to the ICD-11, delirium is essentially featured by disturbed attention and awareness, a careful evaluation of changes in usual behaviors is mandatory. The suspicion, in turn, must direct towards the administration of validated tools. Although the effectiveness of antipsychotics and other pharmacological treatments is still questioned, the use of these drugs is especially necessary for the treatment of hyperactive or mixed delirium featuring severe agitation and self or hetero-injurious behaviors. The hypoactive subtype, although very frequent, is little recognized and requires multicomponent non-pharmacological approaches.
