Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

Objective To assess the rate achieving the target vancomycin trough level (VTL) and its influencing factors in critically ill patients.Methods The retrospective observational study recruited adult patients treated with intravenous vancomycin in the intensive care unit (ICU) at Zhongda Hospital from January 2015 to December 2017.Serum VTL was tested at steady state.Patients' demographics,the sites of infection,microbial culture results,the severity of illness,laboratory data and vancomycin regimen were obtained at the baseline.The rate achieving target VTL (15-20 mg/L) was analyzed based on renal function.Linear regression was performed to determine the influencing factors of VTL.Results A total of 85 patients were enrolled,among whom only 23.5％ (20/85) achieved the target VTL.In patients with normal renal function,the achieving rate was only 11.4％ (4/35),and 80.0％ (28/35) was lower than the target trough level multiple linear regression analysis showed that procalcitonin (PCT),estimated glomerular filtration rate (eGFR) and acute physiology and chronic health disease classification system Ⅱ (APACHE Ⅱ) score were independent factors associated with VTL.Conclusion Achieving target VTL in critically ill patients is not satisfactory.Further study to optimize the administration is needed to facilitate prompt attainment of target VTL.

Objective To investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016.Methods Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation.Results A total of 1183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1124 patients were enrolled. The proportion of men was 36.48% (410/1124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: MoranI = 0.427,Z = 2.646,P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the high-high concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing.Conclusion The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.

BACKGROUNDHigh-frequency oscillatory ventilation (HFOV) allows for small tidal volumes at mean airway pressures (mPaw) above that of conventional mechanical ventilation (CMV), but the effect of HFOV on hemodynamics, oxygen metabolism, and tissue perfusion in acute respiratory distress syndrome (ARDS) remains unclear. We investigated the effects of HFOV and CMV in sheep models with ARDS.

METHODSAfter inducing ARDS by repeated lavage, twelve adult sheep were randomly divided into a HFOV or CMV group. After stabilization, standard lung recruitments (40 cmH2O × 40 seconds) were performed. The optimal mPaw or positive end-expiratory pressure was obtained by lung recruitment and decremental positive end-expiratory pressure titration. The animals were then ventilated for 4 hours. The hemodynamics, tissue perfusion (superior mesenteric artery blood flow, pHi, and Pg-aCO2), oxygen metabolism and respiratory mechanics were examined at baseline before saline lavage, in the ARDS model, after model stabilization, and during hourly mechanical ventilation for up to 4 hours. A two-way repeated measures analysis of variance was applied to evaluate differences between the groups.

RESULTSThe titrated mPaw was higher and the tidal volumes lower in the HFOV group than the positive end-expiratory pressure in the CMV group. There was no significant difference in hemodynamic parameters between the HFOV and CMV groups. There was no difference in the mean alveolar pressure between the two groups. After lung recruitment, both groups showed an improvement in the oxygenation, oxygen delivery, and DO2. Lactate levels increased in both groups after inducing the ARDS model. Compared with the CMV group, the superior mesenteric artery blood flow and pHi were significantly higher in the HFOV group, but the Pg-aCO2 decreased in the HFOV group.

CONCLUSIONCompared with CMV, HFOV with optimal mPaw has no significant side effect on hemodynamics or oxygen metabolism, and increases gastric tissue blood perfusion.

Animals ; Disease Models, Animal ; Hemodynamics ; physiology ; High-Frequency Ventilation ; methods ; Male ; Oxygen ; metabolism ; Positive-Pressure Respiration ; methods ; Respiration, Artificial ; methods ; Respiratory Distress Syndrome, Adult ; metabolism ; therapy ; Sheep

Objective To determine the effect of enhanced hand hygiene on the morbidity of ventilator-associated pneumonia (VAP).Methods Clinical studies which were related to enhanced hand cleansing to the risk of VAP,which were published between July 1992 and June 2013 in English or Chinese were retrieved via computer and manual screening.Data were extracted according to appropriate inclusion and exclusion criteria and analyzed with RevMan 5.0 software.Results A total of 6 studies,all of which were performed with well controlled protocol,involving 28 461 mechanical ventilator days and 32 428 mechanical ventilator days were analyzed.The morbidity of VAP was 39.5 days per 1 000 mechanical ventilator days and 19.5 days per 1 000 mechanical ventilator days before and after enhanced hand cleaning,respectively.The methods of enhancing hand hygiene included feasible hand hygiene apparatus,long-term education,supervision and feedback,as well as increased hand cleaning compliance.All 6 eligible studies reported that enhanced hand washing lowered the risk of VAP,with risk reduction ranging from 29.8％ to 65.5％ with a mean reduction value of 50.6％.Meta analysis showed that enhanced hand cleaning could protect patients from VAP with odds ratio (OR) varying from 1.43 to 5.82 [pooled OR=2.23,95％ confidence interval (95％CI) 1.62-3.07,P＜0.000 01].It was showed in funnel chart that bias in the published articles was not significant.Conclusions Enhanced hand hygiene has an effect of prevention of VAP morbidity and is associated with lowered morbidity of VAP.However,the reliability of this conclusion is questionable because of poor quality of these studies.

ObjectiveTo compare the outcomes of 3 modes of weaning,e.g.SmartCare (a computerdriven knowledge-based system),spontaneous breathing trials (SBBT) and empirical methods,used in patients with chronic obstructive pulmonary diseases (COPD) weaned off mechanical ventilation.MethodsSixty-eight COPD patients were enrolled and randomly (random number) assigned to receive SmartCare (SC group,n =24),SBT (SBT group,n=24) or empirical methods (EM group,n =20).The following data were recorded including beginning of weaning:time consumed for weaning,duration of mechanical ventilation,length of ICU stay,success rate of weaning,survival rate during hospitalization and the complications of mechanical ventilation.The patients were considered as successfully weaned when they were able to tolerate at least 48 consecutive hours of spontaneous breathing.ResultsTime required for weaning and total time for mechanical ventilation in SC group were greatly shorter than those in EM group (P =0.002,0.002),but there were no differences between SC group and SBT group (P =0.540,0.573).Though the length of ICU stay (7.5 d) in SBT group was notably shorter than that in EM group (82.5 d) (P=0.015),there was no difference between SBT group and SC group (8.0 d).Weaning success rate was greater in the SC group (88.3％) than that in EM group (50.0％),but there was no difference between SBT group (66.7％ ) and SC group.No significant differences in survival rate during hospitalization,rate of re-intubation,self-extubation and need for noninvasive ventilation were found among three groups.ConclusionsCompared to empirical methods for weaning,SmartCare could greatly increase the success rate of weaning,but it was not superior to SBT.

Objective To investigate the effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome (ARDS) combined with critical illness-related corticosteroid insufficiency (CIRCI).Methods All early ARDS patients combined with CIRCI were screened by an adrenal corticotrophic hormone (ACTH) test and randomly divided into treatment group (hydrocortisone 100 mg intravenous,3 times/day,consecutively for 7 days,n =12 ) and control group (equivalent normal saline,n =14 ).General clinical data,changes of arterial blood gas,hemodynamics and respiratory mechanics were observed and recorded at admission and at 7 days after treatment.Ventilator-free and shock-free days,ICU stay within 28 days after admission were recorded and 28-day mortality was used as judge prognosis index.Results CIRCI rate in 45 early ARDS patients was 57.8％ ( 26 patients),and the shock rate was markedly higher in ARDS patients with CIRCI than patients without CIRCI (46.2％ vs 5/19 ).There were no significant differences in baseline parameters,oxygenation and illness severity between the treatment and control groups,except for markedly lower lactic level in the treatment group [ 2.7 ( 1.2,3.9 ) mmol/L vs 4.6 ( 2.5,6.3 ) mmol/L,P ＜ O.05].After 7 days of treatment,PaO2/FiO2 markedly increased,while heart rate obviously decreased in the both groups.Compared with the control group,survival time of patients was significantly longer and shock rate of the patients was markedly lower in treatment group within 28 days (5/12 vs 10/14,P ＜ 0.05).The 28-day mortality,which were adjusted by baseline arterial lactic,was lower in the treatment group (2.6/12 ) than in the control group (5.8/14) while with no significant difference ( P ＞ 0.05 ).There was no significant difference in complication incidence between the two groups.Conclusion Stress dose glucocorticoid could reduce shock incidence and prolong survival time,and has a tendency of lower 28-day mortality in early ARDS patients combined with CIRCI.

ObjectiveTo evaluate the association between alveolar dead space fraction and the prognosis of patients with acute respiratory syndrome in the early phase ( ＜ 3 days).MethodsTwentythree patients with ARDS were enrolled in this study.The VD/VT was measured by the single breath test of CO2 (SBT-CO2).The age,heart rate,mean arterial pressure,APACHE Ⅱ,Murray lung injury score,functional residual capacity ( FRC ),PaO2/FiO2,tidal volume,airway plateau pressure ( Pplat ),static pulmonary compliance (Cst),28-day mortality were recorded.ResultsThe alveolar dead-space fraction was markedly elevated (0.59 ±0.06) and the mean FRC was markedly decreased (1643 ±409) ml in the early phase of ARDS.The mortality of 28 days was 52.2％.The mean dead-space fraction was significantly higher in non-survived patients than that in survival [(0.64 ± 0.08 ) vs.(0.53 ±0.04 )].VD/VT was correlated significantly with Murray lung injury score ( r=0.464,P =0.026).The area under the ROC curve for dead space fraction was 0.867,with sensitivity of 83％,and specificity of 82％.Conclusions Increased alveolar dead-space fraction of patients in the early phases of ARDS is associated with greater risk of death.

Objective To evaluate the predictive performance of neuro-mechanical coupling (NMC) and neuro-ventilatory coupling (NVC) in the weaning outcome in patients with chronic obstructive pulmonary disease (COPD). Methods Sixteen patients were enrolled when the criteria for their first spontaneous breathing trial (SBT) was met. A 30-minute SBT was attempted, with the measurement of electrical activity of the diaphragm (Edi) , NMC, NVC, NVC ×NMC, index of rapid shallow breathing (f/Vt) , airway occlusion pressure (P0.1) and f/Vt ×P0.1 at 0, 5 and 30 min. The receiver operating characteristic (ROC) curve was calculated to evaluate the predictive performance of each index. Results Successful weaning(S group) was observed in 6 patients while weaning failure(F group) in 10 patients. (1)The predictive capacity of Edi: at 30 min of SBT, Edi showed higher values in the F group (P ＜ 0. 05), the area under the ROC curves(AUC) was 0. 817(P ＜0. 05). (2) The predictive capacity of NVC and NMC:at 5, 30 min of SBT, NVC and NMC showed higher values in the S group (P ＜0. 05); at 30 min of SBT NVC presented the largest AUC than any other time of SBT (0. 822, P ＜ 0. 05), while the AUC of NMC was 0. 800 (P ＞ 0. 05). (3) The predictive capacity of NVC × NMC: at 30 min of SBT, the AUC of NVC × NMC was larger than NVC (0. 864, P ＜ 0. 05) , showing greater sensitivity (100. 0%) and specificity (83. 3%) .(4) The predictive capacity of f/Vt and P0.1: f/Vt and f/Vt × P0.1 presented poor predictive performance in the failed patients. Conclusions Edi, NVC and NVC × NMC were good predictor for the weaning outcome in patients with COPD.