Clinical Characteristics and Outcomes of Critically ill Mechanically Ventilated COVID-19 Patients Receiving interleukin-6 Receptor Antagonists and/or Corticosteroid Therapy, the INTERACT study: A Multicenter International Observational Study (preprint)

ObjectivesThe interest in interleukin-6 receptor antagonists (IL-6RA) and steroids have increased recently due to their potential role as immunomodulatory effect in critically ill coronavirus disease (COVID-19). The magnitude of this therapy in subgroups of patients with invasive mechanical ventilation (MV) remains to be fully clarified. We compared the clinical characteristics and outcomes of patients requiring iMV, and receiving IL-6RA and steroids with different steroids regimens. DesignInternational, multicenter, observational study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Marginal structural modeling was used to adjust time-dependent confounders; observations were weighted using inverse probability of treatment weight. A sensitivity analysis was conducted for target trial design. Setting168 hospitals, 16 countries. PatientsCovid-19 ICU patients ([≥]18 years) requiring MV between March 01,2020, and January 10,2021. InterventionNone. Measurements and Main ResultsOf 860 patients met eligibility criteria, 589 received steroids, 170 IL-6RA, and 101 combinations; groups were balanced after adjustment. Median daily steroid dose was 7.5 mg dexamethasone or equivalent (IQR:6-14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. The median C-reactive protein level was >75 mg/L in majority of our cohort. The use of IL-6R antagonists alone or in combination was not associated with a significant difference in ventilator-free days (VFD) compared to steroids alone with different steroids regimens (adjusted incidence rate ratio [95% CI]): IL-6R antagonists (1.12 [0.88,1.4]), combination (0.83 [0.6,1.14]). Patients treated with low or high-dose steroids had non-significant differences in VFD compared to IL-6RA ({beta}=0.62, 95% CI -1.54,2.78 for low-dose steroid; {beta}=-1.19, 95% CI -3.85,1.47 for high-dose steroid). There was no difference in 28-day mortality and hospital mortality with IL-6RA alone or in combination compared to steroids alone (28-day mortality adjusted odds ratio [95% CI]): IL-6RA (0.68[0.44,1.07]), combination (1.07[0.67,1.70]). Sensitivity analysis findings were consistent with primary analysis. Liver dysfunction was higher in IL-6RA (p=0.04) while rate of bacteremia did not differ among groups. ConclusionsIn adult ICU COVID-19 patients on iMV, we found no difference in outcomes between those who received IL-6RA, steroids, or combination therapy and those who received IL-6RA or low-or high-dose steroids. Further randomized trials are needed to enhance our understanding for IL-6RA safety with different steroids regimen and the magnitude of benefit in those subgroups of patients.

Modafinil for Wakefulness in the Critical Care Units: A Case Series including COVID-19 Patients at a Tertiary Care Saudi Hospital (preprint)

Cognitive improvement after critical illness is complex. Neuro-stimulants are used to speed up physical and mental processes through the increase in arousal, and wakefulness. In this case series, we reviewed the literature and described the effect of modafinil for wakefulness in a cohort of adult patients admitted to our COVID and non-COVID intensive care unit (ICU) between January 2017 and June 2020. A total of 8 patients included; 3 admitted to COVID-19, 4 surgical, and 1 transplant ICU. Obstructive sleep apnea was noted in 2 (25%), 2 patients (25 %) had an initial neuroimaging that showed hemorrhagic stroke, and 1 (12.5%) showed ischemic stroke with hemorrhagic transformation. Modafinil 100-200 mg daily was started for a median duration of 4 days and the median initiation time in relation to ICU admission was 11 (IQR 9-17) days. Glasgow coma Scale improvement was noted on 5 patients (62.5%). The median duration of mechanical ventilation was 17.5 (IQR 15-31.75) days, and the median ICU stay was 28.5 (IQR 20.25-48) days. All-cause mortality rate was 25 % at 28 days and 62.5 % at 90 days. Modafinil prevented tracheostomy in 1 COVID-19 patient. No significant adverse drug reactions were documented. In our case series, we described our experience for modafinil use for wakefulness in ICU ventilated patients including COVID-19 patients. Based on our observations, the known effects of modafinil, and its safety profile, it holds the potential to facilitate recovery from cognitive impairment. Larger studies are warranted to fully evaluate its role for this indication.