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World J Crit Care Med. Jun 12, 2019; 8(3): 18-27
Published online Jun 12, 2019. doi: 10.5492/wjccm.v8.i3.18
Current controversies and future perspectives on treatment of intensive care unit delirium in adults
Marco Cascella, Marco Fiore, Sebastiano Leone, Domenico Carbone, Raffaela Di Napoli
Marco Cascella, Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples 80049, Italy
Marco Fiore, Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
Sebastiano Leone, Division of Infectious Diseases, “San Giuseppe Moscati” Hospital, Avellino 83100, Italy
Domenico Carbone, Department of Emergency Medicine, Umberto I Hospital, Nocera Inferiore, Salerno 84014, Italy
Raffaela Di Napoli, Department of Anesthesiology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles 1000, Belgium
Author contributions: Cascella M, Fiore M, Leone S, Carbone D and Di Napoli R contributed equally to this manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Marco Cascella, MD, Professor, Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Via Mariano Semmola, 53, Naples 80049, Italy. m.cascella@istitutotumori.na.it
Telephone: +39-81-5903221 Fax: +39-81-5903778
Received: February 28, 2019
Peer-review started: March 4, 2019
First decision: April 11, 2019
Revised: April 19, 2019
Accepted: May 3, 2019
Article in press: May 5, 2019
Published online: June 12, 2019
Abstract

Delirium is the most frequent manifestation of acute brain dysfunction in intensive care unit (ICU). Although antipsychotics are widely used to treat this serious complication, recent evidence has emphasized that these agents did not reduce ICU delirium (ICU-D) prevalence and did not improve survival, length of ICU or hospital stay after its occurrence. Of note, no pharmacological strategy to prevent or treat delirium has been identified, so far. In this scenario, new scientific evidences are urgently needed. Investigations on specific ICU-D subgroups, or focused on different clinical settings, and studies on medications other than antipsychotics, such as dexmedetomidine or melatonin, may represent interesting fields of research. In the meantime, because there is some evidence that ICU-D can be effectively prevented, the literature suggests strengthening all the strategies aimed at prevention through no-pharmacological approaches mostly focused on the correction of risk factors. The more appropriate strategy useful to treat established delirium remains the use of antipsychotics managed by choosing the right doses after a careful case-by-case analysis. While the evidence regarding the use of dexmedetomidine is still conflicting and sparse, this drug offers interesting perspectives for both ICU-D prevention and treatment. This paper aims to provide an overview of current pharmacological approaches of evidence-based medicine practice. The state of the art of the on-going clinical research on the topic and perspectives for future research are also addressed.

Keywords: Delirium, Intensive care, Haloperidol, Antipsychotic agents, Major tranquilizers, Cognitive decline, Dexmedetomidine

Core tip: Delirium represents the most common type of acute brain dysfunction in intensive care unit (ICU). Despite no support from rigorous controlled studies, haloperidol and atypical antipsychotics have been for decades the main class of drugs used for its pharmacological management. Recently, large size studies demonstrated that antipsychotics do not significantly shorten the duration of delirium. However, because ICU delirium has multifactorial pathogenesis it is difficult to postulate that a single agent can be useful for all clinical contexts. In this manuscript we want to provide an overview of most recent pharmacological approaches for the ICU delirium treatment.