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

Objective: 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.