OBJECTIVE:To establish the method for the determination of tigecycline (TGC) in human plasma. METHODS:After precipitated by acetonitrile,the plasma sample was determined by LC-MS/MS. Using d9-TGC as internal standard,Kromasil C18 column was used with mobile phase consisted of water (containing 0.05% TFA)-acetonitrile (gradient elution) at flow rate of 0.6 ml/min,column temperature of 40 ℃. The ion transitions were performed under ESI positive MRM model at m/z 586.3→513.2 and m/z 595.3→514.3 for TGC and internal standard,respectively. RESULTS:The linear range of TGC was 25-2 000 ng/ml (r=0.999 8),and lowest quantification limit was 25 ng/ml;intra-day and inter-day RSD was 3.15%-7.23%,and relative error was-4.53%-10.48%. Plasma sample kept stable after 3 times of freezing and thawing cycle,at room temperature for 24 h,in automat-ic sample injector for 24 h and freezing for 42 d (RSD<15%). Plasma concentration of TGC was 0-438.0 ng/ml in one patient with pan-drug resistant bacteria infection(0-12 h after administration). CONCLUSIONS:The developed method is accurate,sensi-tive and specific,and can be used for plasma concentration determination of TGC and pharmacokinetic study.

Objective To investigate the role of N-myc downstream regulated genes 2 (NDRG2) in attenuation of focal cerebral ischemic-reperfusin injury by sevoflurane preconditioning in rats.Methods Forty-eight healthy male SD rats weighing 280-320 g were randomly divided into 3 groups ( n =16 each):sham operation group (group S),ischemia-reperfusion injury group (group I/R) and sevoflurane preconditioning group (group Sev).Focal cerebral ischemia-reperfusion injury was induced by right middle cerebral artery occlusion (MCAO)for 120 min followed by 24 h reperfusion.In group Sev,2.0％ sevoflurane was inhaled 1 h once a day for 5 consecutive days at 24 h before MCAO.The neurologic function was evaluated at 24 h of reperfusion and than the rats were sacrificed,and the brain was removed for determination of infarct volume percentage,NDRG2 and activated Caspase-3 expression in ischemic penumbra by Western Blot and NDRG2 expression and location by immunohistochemistry.Results The infarct volume percentage,NDRG2 and activated Caspase-3 expression were higher,and neurologic function score was lower in groups I/R and Sev then in group S( P ＜ 0.05).The infarct volume percentage,NDRG2 and activated Caspase-3 expression were lower,and neurologic function score was higher in group Sev then in group I/R ( P ＜ 0.05).The intranuclear NDRG2 positive staining was decreased in group Sev than in group I/R.Conclusion Sevoflurane preconditioning can reduce focal cerebral ischemia-reperfusion injury by inhibiting the expression and activity of NDRG2 and apoptosis in rats.

Objective To explore the application value of short latency somatosensory evoked potentials (SLSEP) as a tool for preoperative assessment of surgical or interventional treatment in patients with severe aneurysmal subarachnoid hemorrhage (aSAH). Methods A prospective observational cohort study was conducted. The patients with severe aSAH with a WFNS grade of Ⅳ or Ⅴ admitted to intensive care unit (ICU) of Beijing Tiantan Hospital of Capital Medical University from November 2016 to April 2017 were enrolled. The patients received SLSEP monitoring within 12 hours after onset, and the monitoring results were classified according to the Judson scale. Meanwhile, the findings on cerebral CT scans at admission were evaluated by the modified Fisher classification. The follow-up was performed at 3 months after aSAH ictus based on the modified Rankin scale (mRS), and a mRS score 0-3 was defined as favorable outcome, 4-6 was defined as unfavorable outcome. For statistical evaluation, demographic, clinical, neuroimaging and SLSEP data were evaluated by univariate analysis to identify the risk factors associated with prognosis;afterwards, those factors were analyzed by multivariate Logistic regression; also the validity was assessed by calculating the respective sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results A total of 41 patients with aSAH were selected, of which 7 were excluded because of the interference of the SLSEP monitoring results, 34 patients with aSAH were enrolled finally. Among them, 21 were classified in the unfavorable outcome group, while the rest (n = 13) were allocated into the favorable outcome group. No significant difference was found in gender, age, body mass index (BMI), time delay from ictus to treatment or the options for therapeutic methods between the two groups. The findings of univariate analysis, however, showed statistically differences in WFNS grade, the modified Fisher scale and Judson scale of SLSEP between the two groups. Yet, the further validity evaluation for these predictors demonstrated that the sensitivity, specificity, PPV and NPV of WFNS grade of Ⅴ and modified Fisher scale of Ⅳ were all less than 85%, whereas the results for SLSEP Judson scale of Ⅲ were much better (sensitivity: 90.5% vs. 71.4% and 71.4%, specificity: 84.6% vs. 69.2% and 76.9%, PPV: 90.5% vs. 79.0% and 83.3%). In the following multivariate Logistic analysis, only Judson scale of Ⅲ was identified to be the independent risk factor for poor outcome [odds ratio (OR) = 45.73, 95% confidence interval (95%CI) = 4.25-499.31, P = 0.002], while the WFNS grade of Ⅴ (OR = 1.14, 95%CI = 0.12-13.06, P = 0.912) and the modified Fisher scale of Ⅳ (OR = 7.22, 95%CI = 0.51-113.20, P = 0.160) were merely associated with poor outcomes without significant independence. Conclusion In comparison with WFNS grade and the modified Fisher scale, SLSEP seems more accurate in the prediction of long-term outcome of severe aSAH prior to surgical or interventional treatment, and thus may be applied as an effective aid in preoperative assessment.

Objective:To investigate the relationship between double-triggering and abnormal movement of air in the lungs (pendelluft phenomenon) under pressure support ventilation (PSV).Methods:A prospective observational study was conducted, postoperative patients admitted to department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University from April 1, 2019 to August 31, 2020 and received invasive mechanical ventilation with PSV mode were enrolled. Electrical impedance tomography (EIT) monitoring was performed. Airway pressure-time, flow-time, global and regional impedance-time curves were synchronously collected and analyzed offline. The volume of abnormal movement of air in the lungs at the beginning of inspiration was measured and defined as pendelluft volume. Double-triggered breaths were identified by trained researchers. Pendelluft volume during double-triggering was measured including the first triggered breath, the double-triggered breath, and the breath immediately following the double-triggered breath. Pendelluft volume was also measured for normal breath during the study. According to the frequency of double-triggering, patients were divided into severe (≥1 time/min) and non-severe double-triggering group. Pendelluft volume, parameters of respiratory mechanics, and clinical outcomes between the two groups were compared.Results:In 40 enrolled patients, a total of 9 711 breaths [(243±63) breaths/patient] were collected and analyzed, among which 222 breaths (2.3%) were identified as double-triggering. The Kappa of interobserver reliability to detect double-triggering was 0.964 [95% confidence interval (95% CI) was 0.946-0.982]. In 222 double-triggered breaths, pendelluft volume could not be measured in 7 breaths (3.2%), but the pendelluft phenomenon did exist as shown by opposite regional impedance change at the beginning of double-triggered inspiration. Finally, pendelluft volume was measured in 215 double-triggered breaths. Meanwhile, 400 normal breaths (10 normal breaths randomly selected for each patient) were identified as control. Compared with normal breath, pendelluft volume significantly increased in the first breath, the double-triggered breath, and the following normal breath [mL: 3.0 (1.4, 6.4), 8.3 (3.6, 13.2), 4.3 (1.9, 9.1) vs. 1.4 (0.7, 2.8), all P < 0.05]. Patients in severe double-triggering, pendelluft volume of normal breath and double-triggered breath were significantly higher than those in non-severe double-triggering group [mL: 1.8 (0.9, 3.2) vs. 1.1 (0.5, 2.1), P < 0.001; 8.5 (3.9, 13.4) vs. 2.0 (0.6, 9.1), P = 0.008]. Patients in severe double-triggering group had significantly higher respiratory rate than that in the non-severe double-triggering group (breaths/min: 20.9±3.5 vs. 15.2±3.7, P < 0.001). There were no significant differences in other respiratory mechanics parameters and main clinical outcomes between the two groups. Conclusions:During PSV, the abnormal movement of air in the lungs (pendelluft phenomenon) was more likely to occur in double-triggering especially in double-triggered breath. The more frequent the double-triggering occurred, the more serious the pendelluft phenomenon was. A higher pendelluft volume of normal breath and a higher respiratory rate were related to severity of double-triggering.

Objective To evaluate the diagnostic validity of application of brainstem auditory evoked potential (BAEP) as an ancillary test in patients with brain death.Methods A prospective observational study was conducted. Adult patients (≥ 18 years) with brain death were consecutively admitted to the Department of Intensive Care Unit (ICU) of Beijing Tiantan Hospital Affiliated to Capital Medical University from July 2015 to June 2017, and they further underwent BAEP monitoring. The following findings: absence of all waveforms at bilateral sides, absence of all waveforms except wave-Ⅰonly present at bilateral orunilateral side were set as the positive criteria of BAEP for the diagnosis of brain death, and its diagnostic sensitivity (SEN), positive predictive value (PPV) and false negative rate (FNR) were further assessed.Results A total of 47 patients were enrolled in the study, and the 43 complete BAEP results were analyzed. The SEN, PPV and FNR of the above 3 types of diagnostic criteria (absence of all waveforms, and unilateral or bilateral presence of wave-Ⅰ only) were 100% [95% confidence interval (95%CI) 90-100], 100% (95%CI 89-100), and 0% (95%CI 0-9), respectively.Conclusion As an ancillary test, BAEP has extremely high validity for the diagnosis of patients with brain death, thus it should be used more extensively in clinical practice.