Background Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant in...Background Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant inhibition, fibrinolytic supression and fibrin deposition. We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces, it could block the procoagulant tendency, lessen depletion of coagulation factors, and even influence the inflammatory response. We also assessed the effects of different administration regimens of heparin. Methods Male Wistar rats were given inhaled heparin starting 30 minutes before （prophylactic heparin） or 2 hours after （therapeutic heparin） intravenous lipopolysaccharide （LPS） was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS. Thrombin-antithrombin complexes, activated protein C, tissue type and urokinase type plasminogen activators （t-PA/u-PA）, plasminogen activator inhibitor-1 （PAl-l）, tumor necrosis factor-a, interleukin-6 in bronchoalveolar lavage, and lung tissue myeloperoxidase activity, and histology score were measured at three time-points. PAI-1/（t-PA ＋ u-PA） was calculated based on the before-mentioned parameters. Statistical analysis was made using one-way analysis of variance （ANOVA） with post hoc test or Student＇s t test in the case of heterogeneity of variance. Results An alveolar procoagulant reaction, depressed fibrinolysis, and inflammatory response occurred in endotoxemia-induced lung injury. Local prophylactic application of heparin attenuated coagulation and early inflammation, promoted fibrinolysis, and reduced the histology score. Therapeutic application of heparin had similar, but weaker effects. Conclusions Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response, promote fibrinolysis, and alleviate pulmonary pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.展开更多
Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult...Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model （NONMEM）, and to investigate the influence of relevant factors in adult patients. Methods Fourteen ASA Ⅰ-Ⅱ patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration （Cpt） was 2.0 μg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90%-95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry （LC-MS/MS）. The population pharmacokinetics analysis was performed using NONMEM program. Results The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-comparment model. Pharmacokintic parameters were clearance （CL）1=0.205 L/min, CL2=0.324 L/min, CL3=0.0292 L/min, volumes of distribution （V）1=4.00 L, V2=2.28 L, V3=4.26 L, Vdss=10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight. Conclusions No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.展开更多
文摘Background Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant inhibition, fibrinolytic supression and fibrin deposition. We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces, it could block the procoagulant tendency, lessen depletion of coagulation factors, and even influence the inflammatory response. We also assessed the effects of different administration regimens of heparin. Methods Male Wistar rats were given inhaled heparin starting 30 minutes before （prophylactic heparin） or 2 hours after （therapeutic heparin） intravenous lipopolysaccharide （LPS） was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS. Thrombin-antithrombin complexes, activated protein C, tissue type and urokinase type plasminogen activators （t-PA/u-PA）, plasminogen activator inhibitor-1 （PAl-l）, tumor necrosis factor-a, interleukin-6 in bronchoalveolar lavage, and lung tissue myeloperoxidase activity, and histology score were measured at three time-points. PAI-1/（t-PA ＋ u-PA） was calculated based on the before-mentioned parameters. Statistical analysis was made using one-way analysis of variance （ANOVA） with post hoc test or Student＇s t test in the case of heterogeneity of variance. Results An alveolar procoagulant reaction, depressed fibrinolysis, and inflammatory response occurred in endotoxemia-induced lung injury. Local prophylactic application of heparin attenuated coagulation and early inflammation, promoted fibrinolysis, and reduced the histology score. Therapeutic application of heparin had similar, but weaker effects. Conclusions Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response, promote fibrinolysis, and alleviate pulmonary pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.
文摘Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model （NONMEM）, and to investigate the influence of relevant factors in adult patients. Methods Fourteen ASA Ⅰ-Ⅱ patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration （Cpt） was 2.0 μg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90%-95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry （LC-MS/MS）. The population pharmacokinetics analysis was performed using NONMEM program. Results The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-comparment model. Pharmacokintic parameters were clearance （CL）1=0.205 L/min, CL2=0.324 L/min, CL3=0.0292 L/min, volumes of distribution （V）1=4.00 L, V2=2.28 L, V3=4.26 L, Vdss=10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight. Conclusions No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.
