Modafinil for Wakefulness and Disorders of Consciousness in the Critical Care Units

  1. Marwa Amer
  2. Mouhamad Ghyath Jamil
  3. Eiad Kseibi

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Abstract

Cognitive improvement after critical illness is complex. Neurostimulants are used to speed up physical and mental processes. Modafinil for wakefulness in the intensive care unit (ICU) holds the potential to facilitate recovery from cognitive impairment. We aim to provide an updated narrative review of the current evidence on modafinil use for wakefulness and disorders of consciousness (DoC) and describe modafinil effect for wakefulness in eight adults admitted to our ICUs at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Methods:

For the narrative review, we searched MEDLINE for modafinil studies as neurostimulant for wakefulness and DoC published from inception through May 30, 2022, with no language or study design restriction, focused on adults, and neurocritical care population (traumatic brain injury [TBI], poststroke). The case series included adult patients (age ≥18 years), admitted between January 2017 and June 2020 to coronavirus disease 2019 (COVID-19) and non-COVID ICUs with an ICU stay of at least 48 h, started on modafinil during ICU stay for at least 48 h and required ventilatory support.

Results:

For the narrative review, we identified five studies in TBI ( n = 285; two RCTs and three retrospective cohort studies), one systematic review poststroke ( n = 120), two studies on ICU population, and one case report describing modafinil use in post-COVID encephalopathy. We also identified additional three recent studies that were published after systematic review for modafinil use poststroke. A total of eight patients out of approximately 10,000–13,000 ICU admissions used modafinil over the 4 years' period and described in our case series; 3 admitted to COVID-19 ICU, 4 surgical ICU, and 1 transplant ICU. Modafinil 100–200 mg daily was started for median duration of 4 days and median initiation time in relation to ICU admission was 11 (IQR 9–17) days. Glasgow Coma Score improvement was noted in 5 (62.5%) patients. No significant adverse effects were documented.

Conclusion:

In this case series, modafinil as neurostimulant was infrequently prescribed in ICU over the 4 years and was associated with a low incidence of adverse effects. Based on our observations, modafinil might have a potential role when administered to certain patients. Our findings can be biased by confounders that influence cognitive function and recovery. Larger studies are warranted to evaluate its role in this indication fully.

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  1. Version published to 10.4103/sccj.sccj_15_22
  2. ScreenIT

    SciScore for 10.1101/2021.02.11.21250832: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Research Ethics Committee and Clinical Research Committee.
    Consent: The patient’s written consent to publish was taken for each case included in the series.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data were collected and managed using institutional Research Electronic Data Capture (REDCap).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Descriptive statistical analysis was conducted using IBM SPSS Statistics, windows version 25.0 (IBM Corp., Armonk, NY).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study limitations were small sample size, single institution experience, retrospective and observational in nature, and lack of a control group which precludes causal interpretations. Similar to other observational studies, our findings can be biased by confounding from unmeasured factors that influence cognitive function and recovery such as the effect of physiotherapy and rehabilitation. It is also plausible that the increasing trend in GCS over time was largely owing to the result of reduced exposure to other sedatives and analgesics and spontaneous recovery. Moreover, patient-family interaction has a great impact in patient recovery as shown in the recent report [43, 44]. In our series, the intensivist on service had the patient described in case 1 interact with the patient’s family through video calling, which likely uplifted his spirit and played a potential role in his recovery. Additionally, the small sample size prohibited us from performing statistical analysis to assess and adjust for confounders or perform analysis of what factors might be associated with response or lack thereof. This may have led to an overestimation or underestimation of modafinil effect for wakefulness in the critical care unit [45]. As is always the case with observation type study, association does not prove causality, but there are reasonable data showing that modafinil might have potential benefits when administered to certain critically ill patients especially those who appear hypoact...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04751227CompletedModafinil for Wakefulness in the Critical Care Units

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.02.11.21250832v1 on medRxiv