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General Management Approach to Delirium

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    All antipsychotics presumably work by blocking the postsynaptic dopamine receptors, primarily in the mesolimbic region. However, simultaneous blockade of striatal dopamine receptors by these agents can cause extrapyramidal side effects (EPS) such as abnormal involuntary movements, akathisia, parkinsonian symptoms, and cogwheeling. The typical antipsychotics such as haloperidol carry a higher risk of EPS. The newer atypical antipsychotics have additional effects on the serotonin system that help reduce the EPS.

    Antipsychotics have a complex mechanism of action with effects on several other neurotransmitter systems. Atypical antipsychotics have been associated with higher risk of weight gain and metabolic issues because of these effects on other neurotransmitter systems. All antipsychotics have been associated with anticholinergic side effects and negative effects on the cardiovascular and cerebrovascular systems, depending on the medication and dosing used.

    Haloperidol, a neuroleptic agent with potent antidopaminergic properties, is still considered the drug of choice for the treatment of delirium in the patient with cancer;[1,7] however, the evidence remains limited. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of hospitalized patients with delirium and acquired immunodeficiency syndrome suggested that haloperidol and chlorpromazine were equivalent in efficacy, and both were associated with a low prevalence of EPS. Lorazepam, however, was ineffective and associated with adverse effects, resulting in early closure of this arm of the protocol.[18][Level of evidence: I] The optimal dose range of haloperidol for patients with delirium has not been determined. Consensus guidelines recommended initial doses in the range of 1 to 2 mg every 2 to 4 hours as needed and lower starting doses, such as 0.5 mg every 4 hours as needed, in elderly patients.[7]

    Haloperidol can be administered orally, intravenously, subcutaneously, or intramuscularly. Parenteral doses are roughly twice as potent as oral doses. Peak plasma concentrations are achieved 2 to 4 hours after an oral dose, and measurable plasma concentrations occur 15 to 30 minutes after intramuscular administration. Haloperidol may cause fewer EPS when administered intravenously. The EPS can be treated with agents such as benztropine in doses of 1 to 2 mg once or twice a day. Neuroleptic malignant syndrome, a rare complication with haloperidol use, is characterized by hyperthermia, increased mental confusion, leukocytosis, muscular rigidity, myoglobinuria, and high serum creatinine phosphokinase. Injectable haloperidol is approved by the FDA only for intramuscular administration. However, it is frequently administered intravenously to treat agitated delirium.

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