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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.
Background Unilateral lung disease (ULD) requiring mechanical ventilation is a unique challenge due to individual and interactive lung mechanics. The distribution of volume and pressure may not be even due to inequities in compliance and resistance. Independent lung ventilation (ILV) is a strategy to manage ULD but is not commonly employed. We assessed the mechanical power (MP) between single lung ventilation (SLV) and ILV in a dual lung model with different compliances. Methods A passive lung model with two different compliances (30 ml/cmH2O and 10 ml/cmH2O) and a predicted body weight of 65 kg was used to simulated ULD and ILV. In SLV the ventilator was set with the following: tidal volume (VT) 400 ml, PEEP 7, RR 20, I:E 1:2. In ILV, each lung was given a separate ventilator with equivalent settings to SLV: VT 300 ml, PEEP 7, RR 20, I:E 1:2 in the more compliant lung (MCL) and VT 100 ml, PEEP 7, RR 20, I:E 1:2 in the less compliant lung (LCL). The study was repeated with different PEEP levels and different ventilator modes, volume (VCV) and pressure control (PCV). PEEP was set according to the compliance: VT 300 ml, PEEP 8, RR 20, I:E 1:2 in the MCL and VT 100 ml, PEEP 10, RR 20, I:E 1:2 in the LCL. The MP in each study and compared SLV to the combined results from each lung in ILV. MP was indexed to the compliance in all the studies Results The MP was significantly lower in VCV compared to PCV in all studies. In VCV, the total MP in SLV was 12.61 J/min compared to 11.39 J/min in the combined lungs with the same PEEP levels (8.84 MCL and 2.55 LCL) (p = < 0.001). The total MP in SLV was also higher when comparing to ILV with different PEEP levels 12.57 J/min (9.43 MCL and 3.01LCL) (p= <0.001). In PCV, the total MP was 14.25 J/min which was higher compared to 13.22 in the combined lungs with the same PEEP levels (9.88 MCL and 3.32 LCL) (p =<0.001) however, the MP was lower compared to 14.55 in the combined lungs with different PEEP levels (10.58 MCL and 3.92 LCL) (p=<0.001).The Power Compliance Index (PCI) was significantly lower in ILV with same PEEP level (0.295 MCL and0.255 LCL, compared to 0.315 in the SLV) and similar in the different PEEP levels (0.314 MCL and , 0.314 LCL, compared to 0.315 in the SLV) in VCV. The PCI was significantly lower in the ILV with the same PEEP level (0.329 MCL, 0.332 LCL compared to 0.356 in the SLV). In the different PEEP levels, the MCL was less (0.352), and higher in the LCL (0.392) compared to the SLV (0.356) in PCV. Conclusions ILV can be achieved with lower MP in VCV using the same or higher PEEP levels than SLV, however in PCV the MP was less using the same PEEP but higher using different PEEP levels. Indexing the MP to compliance can be more meaningful in interpreting the results than the MP alone. Further studies are needed to confirm our findings.
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