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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.
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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.
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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.
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<p><b>BACKGROUND</b>High-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.</p><p><b>METHODS</b>After 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>Compared with CMV, HFOV with optimal mPaw has no significant side effect on hemodynamics or oxygen metabolism, and increases gastric tissue blood perfusion.</p>
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Animals , Male , Disease Models, Animal , Hemodynamics , Physiology , High-Frequency Ventilation , Methods , Oxygen , Metabolism , Positive-Pressure Respiration , Methods , Respiration, Artificial , Methods , Respiratory Distress Syndrome , Metabolism , Therapeutics , SheepABSTRACT
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.
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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.
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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.
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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.
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Objective To investigate the effects of elasticity resistance (Ers) in respiratory system on oxygenation in patients with acute lung injury (ALI) after recruitment maneuvers (RM). Method Meta-analysis of data about the effects of recruitment maneuvers on oxygenation in ALI patients with different elasticity resistances in respiratory system carried out with pooling of study-oriented data stored in Pubmed, Embase, Web of Science databases from January 1999 to June 2010. Results A total of 281 articles were taken, and 20 of them included a sample size of 395 ALI patients. In patients treated with RM in different degrees of respiratory system elasticity resistance ( ≥33.3 cmH2O/L and ＜33.3 cmH2O/L), the effect of RM was better in patients with the high respiratory system elasticity resistance than that with the low one [(51.97 + 8.89) mmHg vs. (35.13 ± 10.33 ) mmHg], P ＜ 0. 01 ), but the high respiratory system elasticity resistance was potentially to lower blood pressure [(4. 33 ± 1.32 ) mmHg vs. (0.22 ± 1.03 ) mmHg],P ＜ 0.01 ). Conclusions This study suggests RM could improve oxygenation of ALI patients with high respiratory system elasticity resistance, and caution must be made to avoid hypotension during RM.
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Objective To investigate the effects of extracorporeal membrane oxygenation (ECMO) on survival of adult from acute respiratory distress syndrome (ARDS). Method We searched Pubmed, Embase, Cochrane Library, Web of Science databases to find relevant literatues on ECMO in treatment of ARDS, which are reported from January 1966 to June 2010. Meta analyses was performed. Results Three papers about randomized controlled trial (RCT) of evaluating ECMO in patients with severe ARDS were enrolled for analyses. Meta-analysis of the three randomized controlled trials revealed ECMO did not decrease the mortality of ARDS patients. However, the cumulative meta-analysis of randomized trials showed ECMO had a protective effect on patients with ARDS. The most recent observational studies suggested that ECMO significantly decreased the mortality of ARDS caused by H1 N1 viral pneumonia. Conclusions There is no evidence to prove the benefit of ECMO in patients with ARDS. However, ECMO should be considered to use in early stage of ARDS as a last rescue resort for potentially reversible severe acute respiratory failure. Further investigation of large sample of high quality RCTs is needed.
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Objective To evaluate the effects of noninvasive positive pressure ventilation (NPPV)used after extubation on mortality and rate of reintubation in patients with acute respiratory failure (ARF).Method Pubmed, Embase, Web of Science databases were searched to collect data from randomized controlled trials (RCT) of the relevant subject from January 1995 to May 2010. Meta analysis of data about NPPV on mortality and rate of reintubation in patients after extubation carried out by using the methods recommended by the Cochrane Collaboration. Results Six RCTs included sample size of 381 NPPV and 379routine medical care. In total, the mortalities of patients in NPPV group and routine medical care group were 18.6% (62/334) vs. 21.6% (72/333), respectively, and the rates of reintubation of the two groups were 30.2% (115/381) vs. 33.5% (127/379), respectively. Compared with routine medical care, NPPV did not significantly reduce the mortality ( OR: 0.83, 95% CI =0.57 ～ 1.21 ,P =0.34) and rate of reintuation( OR: 0.83, 95% CI = 0.59 ～ 1.16, ( P = 0.27). When the analysis was focused to the four studies of them in which patients received NPPV as soon as extubation, the results were quite different. From these four studies, the mortalities of patients in NPPV group and routine medical care group were 12. 2% (22/181) vs.23.9% (44/184),(P=0.004), and the rate of reintubation of the two groups were 14.0% (32/228) vs.20.4% (47/230), (P =0.07). Compared with routine medical care, early application of NPPV to patients after extubation reduced the mortality. Conclusions This study suggests the favorable effects of early application of NPPV to patients after extubation on the mortality of acute respiratory failure.
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Objective To investigate the effects of direct hemoperfusion with polymixin B-immobilized fiber (DHP-PMX) in patients with sepsis. Methods We searched Pubmed, Embase, Web of Science databases and identified relevant randomized controlled trials (RCT) from January 1995 to May 2010. Meta-analysis of DHP-PMX on mortality and levels of endotoxin in patients with sepsis were conducted using the methods recommended by the Cochrane Collaboration. Results Eleven RCTs were included.Eight of them included the mortality of patients (sample size: 211 DHP-PMX and 178 conventional medical therapy). In total, the mortalities of patients with sepsis in DHP-PMX group and conventional group were 37.4% (79/211) and 68.5% (122/178) respectively. Compared with the conventional medical therapy,DHP-PMX appeared to significantly reduce mortality ( OR =0.24,95% CI 0.16-0.38 ,P ＜0.000 01 ). The results were similar when two RCTs enrolling patients with methicillin resistant staphylococcus aureus (MRSA) infections were excluded( OR =0. 27,95% CI 0. 17-0. 45, P ＜0. 000 01 ). When the analysis was limited to the nine studies that reported 28- to 30-day mortality, results were unchanged( OR =0. 29,95% CI 0.17-0.48 ,P ＜0.000 01 ). Six RCTs had the available data of endotoxin. The level of endotoxin decreased 31 ng/L(95% CI 22.46-39.55 ) after DHP-PMX therapy, and the decreasing was statistically significant (P＜0. 000 01 ) ,while the level of endotoxin in patients of conventional group did not change (P =0.94).Conclusions This study suggests a favorable effects of DHP-PMX on mortality and endotoxin decreasing in patients with sepsis. However, lack of enough cases and blinding need to be considered. Further investigation with large sample of high quality RCTs is needed.
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ObjectiveTo evaluate the value of dead space fraction (VD/VT) guided positive end expiratory pressure ( PEEP ) in acute respiratory distress syndrome ( ARDS ).Methods Twenty-three intubated and mechanically ventilated patients with early ARDS were enrolled in the study.PEEP was titrated by lowest VD/VT.Parameters of oxygenation and respiratory mechanics were observed.Results PEEP titrated by lowest VD/VT and highest static lung compliance ( CLst ) ( P ＞ 0.05 ) respectively,were lower than PEEP titrated by optimal oxygenation ( P ＜ 0.05),but there was no significant difference between lowest VD/VT and highest Ctst method.The VD/VT that ventilated on PEEP titrated by the lowest VD/VT decreased than its basal level.There was no difference significantly between the VD/VT that ventilated on PEEP elected by the other two methods with basal level ( P ＞ 0.05 ).The the ratio of arterial PO2 to the inspired oxygen fraction (PaO2/FiO2)ratios improved significantly than the baseline values in three ventilation strategies,and that ventilated on PEEP targeting the lowest VD/VT was lower than PEEP targeting optimal oxygenation.The plateau airway pressure that ventilated on PEEP targeting optimal oxygenation was higher than the other two methods.The functional residual capacity (FRC) of patients ventilated by PEEP targeting optimal oxygenation was increased than the lowest VD/VT and maximum CLst.Conclusions VD/VT could be one of the methods to titrate the optimal PEEP in patients with early ARDS.Optimal PEEP targeting the highest compliance in conjunction with the lowest dead space fraction indicated a maximumamount of effectively expanded alveoli.
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Objective To assess the value of pulmonary vascular permeability index in differentiating acute lung injury (ALI) from cardiac pulmonary edema. Methods Critically ill patients with acute pulmonary edema were included from May, 2004 to September, 2008. Patients were divided into two groups, the ALI group and the cardiac pulmonary edema group (C group). Pulmonary vascular permeability index (PVPI) , intrathoracic blood volume (ITBVI) were determined by pulse indicator continuous cardiac output(PiCCO) system. Results ( 1 ) Thirty-four patients were enrolled, 22 cases in ALI group and 12 cases in C group. (2) The PVPI in patients of ALI group (2.7 ± 1.4) was higher than that of C group (1.9 ±0.6 ;P＜0.05). EVLWI and ITBVI did not have the significant difference between the two groups (P ＞0. 05). (3) PVPI was positively correlated with EVLWI(r = 0. 762) , negatively correlated with PaO2/ FiO2(r= -0.478). (4)ARDS was diagnosed in 13 cases, including 8 pulmonary cause(ARDSp) and 5 extra-pulmonary cause ( ARDSexp). PVPI, EVLW/ITBV and EVLWI of patients with ARDSexp were obviously higher than those with ARDSp. Conclusions PVPI may be useful for differentiating the types of pulmonary edema in the critically ill.
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Objective To evaluate the effects of positive end-expiratory pressure (PEEP) targeting optimal oxygenation on local gas distribution and inflammation in dogs with acute respiratory distress syndrome (ARDS). Methods ARDS was induced by saline alveoli-lavage and oleic acid intravenous. The animals were mechanical ventilated 4 h at optimal PEEP titrated by oxygenation. Computed tomography (CT) scans were performed before and after induction of ARDS and at the end the study. NF-κB was measured by electrophoretic mobility shift assay (EMSA), IL-6 and IL-10 were assessed by ELISA.Myeloperoxidase (MPO) and malondialdehyde (MDA) were measured. Pathological changes were examined under optical microscope. Results (1) Compared to baseline, total lung volumes decreased and nonaerated areas increased significantly after the induction of ARDS in both groups (P ＜ 0.05 ). Compared with ARDS models, PEEP titrated to achieve optimal oxygenation resulted in greater lung recruitment but was accompanied with hyperinflation, hyperinflation occurred in non-dependent lung. Compared with oleic acidinjured ARDS, the changing of hyperinflated lung areas was increased markedly in saline lavage-injured ARDS (P＜0.05). (2) Compared with right lung ventral lower lobe, lung injury score was lower in right lung upper lobe. Histological injury in right lung dorsal lower lobe was severer than that in right lung upper lobe and right lung ventral lower lobe. NF-κB activation of right lung dorsal lower lobe was markedly higher than right lung upper lobe (P ＜ 0.05 ). MPO and MDA were much higher with right lung dorsal lower lobe than right lung upper lobe and right lung ventral lower lobe ( P ＜ 0.05 ). Compared with right lung upper lobe and right lung ventral lower lobe, IL-6 and IL-10 increased markedly in right lung dorsal lower lobe ( P ＜ 0.05 ). Conclusions Alveolar hyperinflation and aggravated lung injury in non-dependent region were occurred at PEEP targeting optimal oxygenation. Hyperinflation was more common in saline lavage-injured ARDS.
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Objective To systematically review the efficacy of dexmedetomidine or midazolam for sedation in critically ill patients. Methods We searched the PubMed, EMBaes, Cochrane Library, Wanfang Database,CNKI and VIP for all randomized controlled trials (RCTs) about the efficacy of dexmedetomidine versus midazolam for sedation in severe cases. The quality of the studies was evaluated by the method recommended by Cochrane Collaboration. Meta-analysis was conducted using the Cochrane Collaboration's RevMan 5.0 software. Results Six RCTs involving 613 patients were included in our Meta-analysis. The results of Meta-analysis showed that the length of ICU stay was significantly shorter in group dexmedetomidine than in group midazolam. There were no significant differences in the duration of mechanical ventilation, incidences of bradycardia, hypotension and delirium and mortality rate between the two groups. Conclusion Dexmedetomidin can shorten the length of ICU stay and is beneficial for the outcome in critically ill patients.
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Objective: To establish the method of percutaneous endoscopic gastrostomy(PEC) and percutaneous endoscopic jejunostomy (PEJ) for enteral nutrition. Methodes: PEG tubes were placed in 114 patients with Pull method. On the foundation of PEG, PEJ tubes were placed in 26 patients by pushing endoscopy to send tubes through Treitz ligment with usingthe the clip. Results: All PEG insertion was performed successfully. PEJ tubes were placed successfully with a new method in 26 patients. 15 patients had a little blooding and 8 patients had slight infection. 21 patients had respiratory tract infection and had been cured by using antibiotic. There was no severe complication. Conclusion: PEG is simple、safe、efficient. The new method of PEJ is feasible.