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Aripiprazole for prevention of delirium in the neurosurgical intensive care unit: a double-blind, randomized, placebo-controlled study

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Abstract

Purpose

Delirium is reported in over 50% of critically ill ICU patients, and is associated with increased mortality and long-term cognitive consequences. Prevention and early management of delirium are essential components of ICU care. However, pharmacological interventions have not been effective in delirium prevention. This study investigated the effect of aripiprazole in the prevention of delirium in a neurosurgical intensive care unit.

Methods

In this prospective, randomized placebo-controlled small clinical trial, 53 patients, 18 to 80 years old, were randomized to receive enteric aripiprazole (15 mg) or placebo for up to 7 days. Delirium, detected by the Confusion Assessment Method-ICU, ICU events, laboratory studies, aripiprazole safety, time to delirium onset, delirium-free days, delirium prevalence during follow-up and ICU length of stay were recorded.

Results

Forty patients with similar baseline characteristics, including age, sex, neurosurgery types and APACHE II scores, completed the study. Delirium incidence and the mean days to its onset were 20% vs. 55% (p = 0.022) and 2.17 ± 0.41 vs. 2.09 ± 0.30 (p = 0.076) in the aripiprazole and placebo groups, respectively. The mean number of delirium-free days were: 5.6 (95%CI, 4.6-6.5) and 4.3 (95%CI, 3.2-5.4), in aripiprazole and placebo groups, respectively (p = 0.111). The prevalence of delirium during the follow-up was significantly lower in the aripiprazole group (p = 0.018). Serious aripiprazole adverse reactions were not observed.

Conclusions

Aripiprazole can reduce the incidence of delirium in the neurosurgical ICU. Studies with larger sample size in diverse ICU settings and longer follow-up are needed to confirm our findings.

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Abbreviations

ICU:

Intensive care unit

CAM-ICU:

Confusion Assessment Method for the ICU

EPS:

Extrapyramidal syndrome

TBI:

Traumatic brain injury

SAH:

Subarachnoid hemorrhage

IQCODE:

Informant Questionnaire on Cognitive Decline in the Elderly

RASS:

Richmond Agitation–Sedation Scale

APACHE-II:

Acute Physiology and Chronic Health Evaluation II

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Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, Imam Hossein Teaching and Educational Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Majid Mokhtari

  2. Department of Clinical Pharmacy, School of Pharmacy-International Campus. Firoozgar Clinical Research Development Center (FCRDC), Iran University of Medical Sciences, Tehran, Iran

    Maryam Farasatinasab

  3. Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mina Jafarpour Machian

  4. Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Yaseri

  5. Department of Neurosurgery, Firoozgar Teaching and Educational Center, Iran University of Medical Sciences, Tehran, Iran

    Mohammad Ghorbani, Seyed Mahmood Ramak Hashemi & Navid Golchin

  6. Department of Neurosurgery, Firoozgar Clinical Research Development Center (FCRDC), Iran University of Medical Sciences, Tehran, Iran

    Mehdi Nikoobakht

  7. Department of Neurosurgery, Firoozgar Clinical Research Development Center (FCRDC), Iran University of Medical Sciences, Firoozgar Teaching and Educational Center, Tehran, Iran

    Gholamhasan Mohammadi

  8. Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Sistanizad

  9. Department of Pharmaceutical Care Unit, Imam Hossein Medical and Educational Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Sistanizad

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  1. Majid Mokhtari
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Contributions

MM and MS created the concept. Literature review and drafting of the proposal were done by MF and MJ. MG, SMRH, MN, NG, and GM performed the search and gathered clinical data. MY analyzed the data. All authors reviewed and helped to finalize the article for publication.

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Correspondence to Mohammad Sistanizad.

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All authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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This study was performed at Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

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Mokhtari, M., Farasatinasab, M., Jafarpour Machian, M. et al. Aripiprazole for prevention of delirium in the neurosurgical intensive care unit: a double-blind, randomized, placebo-controlled study. Eur J Clin Pharmacol 76, 491–499 (2020). https://doi.org/10.1007/s00228-019-02802-1

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