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Background Cefepime-induced neurotoxicity (CIN) has been well acknowledged among clinicians, although there are no clear diagnostic criteria or specific laboratory testing to help with its diagnosis. We aimed to summarize the existing evidence regarding CIN and provide future agendas for research. Methods Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and Embase for all peer-reviewed articles using keywords including ‘cefepime’, ‘neurotoxicity’, ‘encephalopathy’ and ‘seizure’, from their inception to 20 January 2022. Results We included 92 articles, including 23 observational studies and 69 cases from case reports and case series, in the systematic review. Among 119 patients with CIN, 23.5% were in the ICU at the time of diagnosis and nearly 90% of the cases showed renal dysfunction. Cefepime overdoses were described in 41%. The median latency period of developing CIN from cefepime initiation was 4 days, and about 12% developed CIN during empirical treatment. CIN patients commonly manifested altered mental status (93%), myoclonus (37%) and non-convulsive seizure epilepticus (28%). A serum cefepime trough level of >20 mg/L would put patients at risk for CIN. CIN-related symptoms were ameliorated in 97.5% by dose reduction or discontinuation of cefepime, with median time to improvement of 3 days. No CIN-associated deaths were reported. Conclusions This systematic review summarizes the current evidence and characteristics of CIN. In the current situation where there are no CIN diagnostic criteria and the drug monitoring platform is not routinely available, candidates for cefepime should be carefully selected. Also, based on these findings, it needs to be appropriately dosed to avoid the development of CIN.

Introduction Mechanical power has been linked to ventilator induced lung injury and mortality in acute respiratory distress syndrome (ARDS). Adaptive Ventilator Mode-2 is a closed-loop pressure-controlled mode with an optimal targeting scheme based on the inspiratory power equation that adjusts the respiratory rate and tidal volume to achieve a target minute ventilation. Conceptually, this mode should reduce the mechanical power delivered to the patients and thus reduce the incidence of ventilator induced lung injury. Methods A bench study using a lung simulator was conducted. We constructed three passive single compartment ARDS models (Mild, Moderate, Severe) with compliance of 40, 30, 20 ml/cmH2O respectively, and resistance of 10 cmH2O/L/s, with IBW 70 kg. We compared three different ventilator modes: AVM-2, Pressure Regulated Volume Control (PRVC), and Volume Controlled Ventilation (VCV) in six different scenarios: 3 levels of minute ventilation 7, 10.5, and 14 Lit/min (Experiment 1, 2, and 3 respectively), each with 3 different PEEP levels 10, 15, and 20 cmH2O (Experiment A, B, and C respectively) termed 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B, 3C respectively for a total of 81 experiments. The AVM-2 mode automatically selects the optimal tidal volume and respiratory rate per the dialed percent minute ventilation with an I:E ratio of 1:1. In the PRVC and VCV (constant flow) we selected target tidal volume 6ml/kg/IBW (420 ml) and respiratory rate adjusted to match the minute ventilation for the AVM-2 mode. I:E ratio was kept 1:2. The mechanical power delivered by the ventilator for each mode was computed and compared between the three modes in each experiment. Statistical analysis was done using Kruskal-Wallis test to analyze the difference between the three modes, post HOC Tukey test was used to analyze the difference between each mode where P < 0.05 was considered statistically significant. The Power Compliance Index was calculated and compared in each experiment. Multiple regression analysis was performed in each mode to test the correlation of the variables of mechanical power to the total calculated power. Results There were statistically significant differences (P < 0.001) between all the three modes regarding the ventilator delivered mechanical power. AVM-2 mode delivered significantly less mechanical power than VCV which in turn was less than PRVC. The Power Compliance index was also significantly lower (P < 0.01) in the AVM-2 mode compared to the other conventional modes. Multiple regression analysis indicated that in AVM-2 mode, the driving pressure (P = 0.004), tidal volume (P < 0.001), respiratory rate (P = 0.011) and PEEP (P < 0.001) were significant predictors in the model. In the VCV mode, the respiratory rate (P 0< 0.001) and PEEP (P < 0.001) were significant predictors, but the driving pressure was a non-significant predictor (P = 0.08). In PRVC mode, the respiratory rate (P < 0.001), PEEP (P < 0.001) and driving pressure (P < 0.001) were significant predictors. Conclusion AVM2 mode delivered less mechanical power compared to two conventional modes using low tidal volume in an ARDS lung model with different severities. This might translate to the reduction of the incidence of ventilator induced lung injury. Results need to be validated in clinical studies.

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Selective androgen receptor modulators (SARMs) are novel nonsteroidal agents abused for performance enhancement such as anabolic steroids. We report a case of a 27-year-old man who used 3 different SARMs and presented with progressive weakness. Initial laboratory testing showed kidney and liver injury with creatinine 4.8 mg/dL and total bilirubin 43.3 mg/dL. An extensive workup was negative for other causes, and the results of liver and kidney biopsies were consistent with bile cast nephropathy because of SARM-associated drug-induced liver injury. His organ functions improved with the cessation of SARMs and plasmapheresis. Providers need to recognize the extreme consequences of SARM use.