Journal of Clinical & Experimental Pharmacology

Abstract

Assessment of Safety of Haloperidol in the Presence of Other QT Prolonging Drugs in the Intensive Care Unit

J. MCLUCKIE

ICU delirium is a common neuropsychiatric disorder, characterized by an acute fluctuation in consciousness. Haloperidol is used routinely in ICUs to both treat and prevent delirium, which strikes up to half of ICU patients and is associated with prolonged mechanical ventilation, longer ICU and hospital stays, and increased mortality. Haloperidol, the major tranquilizer par excellence, was synthesized 60 years ago in February 1958. Since then it has been used in hundreds of thousands of patients with schizophrenia and other psychoses, particularly for the management of psychosis-induced agitation , and is included in the World Health Organization’s list of essential medicines. In 1974–1975, Seeman, by using a preparation of rat brain striatum, discovered that haloperidol selectively blocked the D2 dopamine receptors. This hypothesis also provides a biological basis to explain the observed efficacy of haloperidol not only in schizophrenia but also in delirium. Dopamine excess may cause some of the neurobehavioral alterations observed in patients with hyperactive or mixed type delirium, namely agitation, restlessness, irritability, increased psychomotor activity, distractibility, hyperlertness, combativeness, and psychotic distressing symptoms. This explains why dopaminergic drugs, such as the levodopa, can precipitate delirium, while dopamine antagonists like haloperidol and other antipsychotics can effectively control the behavioral signs of delirium. Dopamine D2 antagonists enhance acetylcholine release, which may be another mechanism by which these drugs help to alleviate the symptoms of delirium . Based on this multiplicity of effects, some experts suggest that haloperidol and other antipsychotic agents may be effective not only in the management of behavioral symptoms of delirium (agitation), but they might also be useful in patients with hypoactive delirium to control distressing psychotic symptoms such as hallucinations and delusions.

Published Date: 2020-12-25; Received Date: 2020-11-04