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We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
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Humans , Consensus , Critical Care/methods , Intensive Care Units , Pain/drug therapy , Analgesics/therapeutic use , Delirium/therapy , Critical IllnessABSTRACT
Objectives To learn the echocardiography skills of intensivists after receiving a basic critical care echocardiography training course, and investigate factors that may influence their performance. Methods We completed a web-based questionnaire that assessed the skills in ultrasound scanning techniques of intensivists who took a training course on basic critical care echocardiography held in 2019 and 2020. Mann-Whitney test was used to analyze the factors which might affect their performance on image acquisition, recognizing clinical syndrome, and measuring the diameter of inferior vena cava, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral.Results We enrolled 554 physicians from 412 intensive care units across China. Among them, 185 (33.4%) reported that they had 10%-30% chance of being misled by critical care echocardiography when making therapeutic decision, and 34 (6.1%) reported that the chance was greater than 30%. Intensivists who performed echocardiography under the guidance of a mentor and finished ultrasound scanning more than 10 times per week reported significant higher scores in image acquisition, clinical syndrome recognition, and quantitative measurement of inferior vena cava diameter, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral than those without mentor and performing echocardiography 10 times or less per week respectively (all P < 0.05).Conclusion The skills in diagnostic medical echocardiography of Chinese intensivists after a basic echocardiographic training course remain low, and further quality assurance training program is clearly warranted.
Subject(s)
Humans , Clinical Competence , East Asian People , Echocardiography/standards , Stroke Volume , Ventricular Function, Left , Self-Assessment , Physicians/standards , Internal Medicine/standardsABSTRACT
Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%
Subject(s)
Humans , Critical Illness , Cross-Sectional Studies , Echocardiography , Intensive Care Units , Lung/diagnostic imaging , Retrospective StudiesABSTRACT
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The heart is one of the most important oxygen delivery organs, and dysfunction significantly increases the mortality of the body. Hence, the heart has been studied in sepsis for over half a century. However, the definition of sepsis-induced cardiomyopathy is not unified yet, and the conventional conception seems outdated: left ventricular systolic dysfunction (LVSD) along with enlargement of the left ventricle, recovering in 7 to 10 days. With the application of echocardiography in intensive care units, not only LVSD but also left ventricular diastolic dysfunction, right ventricular dysfunction, and even diffuse ventricular dysfunction have been seen. The recognition of sepsis-induced cardiomyopathy is gradually becoming complete, although our understanding of it is not deep, which has made the diagnosis and treatment stagnate. In this review, we summarize the research on sepsis-induced cardiomyopathy. Women and young people with septic cardiomyopathy are more likely to have LVSD, which may have the same mechanism as stress cardiomyopathy. Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction. Patients with mechanical ventilation, acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction. Diffuse cardiac dysfunction has also been shown in some studies; patients with mixed or co-existing cardiac dysfunction are more common, theoretically. Thus, understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.
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Objective This study aimed to determine which parameters in transthoracic echocardiography (TTE) are more likely to be affected when applied in a critical care setting with mechanical ventilation.Methods Ninety mechanically ventilated ICU patients were enrolled into the study group. The control group consisted of 90 patients who underwent interventional therapy. All patients had bedside TTE for parametric measurements including the right ventricular size, septal kinetics and left ventricular ejection fraction (LVEF) by eyeballing (visual assessment), the tricuspid annular plane systolic excursion (TAPSE), mitral annular plane systolic excursion (MAPSE) by M-mode sonography, the right ventricular outflow tract velocity-time integral (RVOT VTI) and left ventricular outflow tract velocity-time integral (LVOT VTI) by pulse-Doppler, the right ventricular fraction of area change (FAC) and left ventricular ejection fraction (LVEF Simpson) by endocardium tracing. We compared the differences in the frequency of optimal image acquisition in assessments of these parameters between the two groups, as well as the differences in acquisition rates of parameter measurements in ventilated ICU patients.Results There were significantly fewer patients in the study group than in the control group who had optimal images acquisitions for parameter assessments with M-mode method, pulse Doppler method and endocardium-tracing method (
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BACKGROUND@#Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients' kidney function recovery.@*METHODS@#A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients' renal function recovery at discharge, fluid balance, and levels of CVP were assessed.@*RESULTS@#A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI.@*CONCLUSION@#Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.
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Background@#Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients’ kidney function recovery.@*Methods@#A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients’ renal function recovery at discharge, fluid balance, and levels of CVP were assessed.@*Results@#A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ2 = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ2 = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI.@*Conclusion@#Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.
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Objective: To explore the effect and mechanism of genistein on oleic acid-induced lipid accumulation in HepG2 cells. Method: Lipid accumulation model in HepG2 cells was induced by different concentrations of oleic acid for 24 h, and 12.5, 25, 50 μmol·L-1genistein and oleic acid acted on cells for 24 h. Cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Double staining with Nile red and DAPI was used to observe the intracellular lipid droplets. Intracellular triglyceride (TG) content was determined by kit. The protein expression levels of triglyceride lipase(ATGL),hormone-sensitive fatty acid(HSL),phosphorylation HSL(p-HSL),silent information regulator 1(STRT1),peroxisome proliferator-activated receptor α(PPARα),carnitine palmityl transferase 1(CPT-1) in oleic acid-induced HepG2 cells were detected by Western blot. Result: 0.5 mmol·L-1 oleic acid and 12.5, 25, 50 μmol·L-1 genistein had no significant effect on cell viability after treated cells for 24 h. Compared with normal group, the TG content and lipid droplets in oleic acid-induced HepG2 cells was significantly increased (PPPPα, and CPT-1 compared with model group (PPConclusion: Genistein can significantly improve the lipid accumulation in oleic acid-induced HepG2 cells, and its mechanism may be related to up-regulating the protein expression levels of ATGL, p-HSL/HSL, SIRT1, PPARα, CPT-1, and thus promoting lipid hydrolysis and oxidative metabolism.
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BACKGROUND@#Increased right ventricle afterload during acute respiratory distress syndrome (ARDS) may induce acute cor pulmonale (ACP), which is associated with a poor clinical outcome. Echocardiography is now considered as a rapid and non-invasive tool for diagnosis of ACP. The aims of this study were to investigate the morbidity and mortality rates of ACP in ARDS patients in intensive care units (ICUs) across the mainland of China and to determine the severity and prognosis of ACP in ARDS patients through an ultrasound protocol (TRIP). And the association between ACP related factors and the ICU mortality will be revealed.@*METHODS@#This study is a multicenter and cross-sectional study in China which will include ICU participants when diagnosed as ARDS. The ultrasound protocol, known as the TRIP, is proposed as severity assessment for ACP, which includes tricuspid regurgitation velocity (T), right ventricular size (R), inferior vena cava diameter fluctuation (I), and pulmonary regurgitation velocity (P). The 28-day mortality, ICU/hospital mortality, the length of stay in ICU, mechanical ventilation days, hemodynamic parameters and lab parameters of liver function and kidney function are all recorded.@*DISCUSSION@#This large-scale study would give a sufficient epidemic investigation of ACP in ARDS patients in China. In addition, with the TRIP protocol, we expect that we could stratify ACP with more echocardiography parameters.@*TRIAL REGISTRATION@#NCT03827863, https://clinicaltrials.gov/ct2/show/NCT03827863.
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·AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration. · METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total). The concentrations of the metabolites of diacerein in the cornea were measured by high performance liquid chromatography after given eye drop 5, 15, 30, 60, 120, and 180min. The pharmacokinetic parameters were calculated by pharmacokinetic software (DAS2.1.1). ·RESULTS: The metabolites of diacerein, rhein, was detected in the cornea at each time point. The concentration of the metabolite of diacerein in the cornea was 318.678±40.88,210.02±25.66,188.83±31.74,112.24± 11.70,90.28±22.01 and 57.67±13.71μ g/g after given eye drop 5, 15, 30, 60, 120, and 180min in the multiple administration group. The concentration in the single administration group was 145.17 ± 19.29, 97.95 ± 10.49, 71.18±18.70,39.11±2.44,18.10±2.34 and 9.08±2.04μ g/g respectively. The concentration of rhein in the cornea was the highest at 5min after the administration in the two groups. The concentration of the multiple administration group was higher than that in the single administration group at 5, 15, 30, 60, 120, and 180min (P<0.01). The half-life of the drug was 0.89 ± 0.31h in the single administration group. · CONCLUSION: Compared with the single administration, the conjunctival sac multiple administration has the advantages of high drug concentration and long duration. Therefor the conjunctival sac multiple administration is a more effective method to treat acute infectious corneal diseases.
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Objective To compare the removal efficiency of γδT cells between cornea and ear skin and develop an alternative method for dynamic monitoring of γδT cells in mouse cornea in vivo using 2-photon laser scanning microscopy.Methods The γδT cells in mouse ear skin were monitored before and after antibody neutralization,and the mice corneas were excised and stained for counting γδT cells at 6 h,12 h,24 h after antibody neutralization by using 2-photon laser scanning microscopy,followed by comparison of the removal efficiency of γδT cells between the cornea and ear skin.Results The γδT cells in normal mouse cornea were often distributed in the limbal epithelium and superficial stromal layer.The irregular morphology of γδT cells in the epithelial layer was often accompanied by protuberances,while the stromal γδT cells were mostly round or oval and the number of cells was approximately 27 ± 4.After antibody neutralization,the number of γδT cells in the cornea of mice gradually decreased,and the number of cells at 6 h,12 h and 24 h was significantly lower than that of before depletion (P =0.03,0.00,0.00),and the removal efficiencies were 48%,78%,and 96%,respectively.The γδT cells in ear skin of the normal mice were ellipse or stellate with cell processes and they were located in epidermal layer,and the cell number was about 60 ± 9.After antibody neutralization,the number of γδT cells were significantly reduced at 6 h,12 h and 24 h compared with before depletion (P =0.000,0.000,0.000) and the removal efficiency were 43%,72% and 95%,respectively.Conclusion The number of γδT cells in the cornea and ear skin is gradually decreased after antibody neutralization,and their removal efficiency is consistent with time.Therefore,monitoring the γδT cells in the mouse ear skin is an ideal alternative to dynamically monitoring the changes in the number of γδT cells in the cornea in vivo.
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Objective To investigate the effect of target-and-endpoint protocol on the resuscitation of septic patients.Methods This is a retrospective study performed at the Peking Union Medical College Hospital Intensive Care Unit. We enrolled 545 septic patients who needed vasopressors on at least the first day of ICU admission. The general characteristics, blood lactate level, mean arterial pressure (MAP), central venous pressure (CVP) and saturation of central venous oxygen (ScvO) at admission and 6, 24 hours after admission were collected. The parameters at different time points were compared. Lactate clearance rate and in-hospital mortality were analyzed.Results The 6-hour lactate clearance rate was 21.6% (IQR, 8.6%-39.0%), and in-hospital mortality was 9.4%. For patients with low CVP values (<8 mm Hg, 1 mm Hg=0.133 kPa) at admission, CVP increased significantly at 6 hours after admission (5.4±1.6 mm Hg vs. 7.7±2.6 mm Hg, P<0.001). For patients with low MAP (<75 mm Hg) at admission, the MAP values increased significantly at 6 hours (64.2±7.1 mm Hg vs. 82.2±13.1 mm Hg, P<0.001). For patients with low ScvO value (<70%) at admission, the ScvO value increased significantly at 6 hours (61.9%±7.0% vs. 71.9%±7.8%, P<0.001). No difference was found between the values at 6 hours and the corresponding values at 24 hours after admission. For patients with high CVP values (≥8 mm Hg) at admission, CVP decreased significantly at 6 hours (11.3±4.0 mm Hg vs. 10.3±2.9 mm Hg, P<0.001). For patients with high MAP (≥75 mm Hg) at admission, the MAP values decreased significantly at 6 hours (94.2±13.9 mm Hg vs. 89.4±11.4 mm Hg, P<0.001). For patients with high ScvO value (≥70%) at admission, the ScvO values decreased significantly at 6 hours (76.8%±4.2% vs. 72.9%±7.3%, P<0.001). No difference was found between the values at 6 hours and the corresponding values at 24 hours.Conclusions This study suggested that in the resuscitation of sepsis and septic shock patients in the ICU, the target values did not need to be within the "normal range" recommended by early-goal directed therapy. The "target-and-endpoint" protocol, which aimed for personalized goals, deserves more consideration.
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<p><b>OBJECTIVE</b>Continuous renal replacement therapy (CRRT) is a continuous process of bedside blood purification which is widely used in the treatment of acute kidney injury (AKI) and for fluid management. However, since AKI and fluid overload are often found to be associated with hemodynamic abnormalities, determining the relationship between CRRT and hemodynamics remains a challenge in the treatment of critically ill patients. The aim of this review was to summarize key points in the relationship between CRRT and hemodynamics and to understand and monitor renal hemodynamics in critically ill patients, especially those with AKI.</p><p><b>DATA SOURCES</b>This review was based on data in articles published in the PubMed databases up to January 30, 2017, with the following keywords: "continuous renal replacement therapy," "Hemodynamics," and "Acute kidney injury."</p><p><b>STUDY SELECTION</b>Original articles and critical reviews on CRRT were selected for this review.</p><p><b>RESULTS</b>CRRT might treat AKI by hemodynamic therapy, and it was an important form of hemodynamic therapy. The targets of hemodynamic therapy should be established when using CRRT. Therefore, hemodynamic management and stability were very important during CRRT. Most studies suggested that renal hemodynamics should be clearly identified.</p><p><b>CONCLUSIONS</b>CRRT is not only a replacement for organ function, but an important form of hemodynamic therapy. Improved hemodynamic management of critically ill patients can be achieved by establishing specific therapeutic hemodynamic targets and maintaining circulatory stability during CRRT. Over the long term, observation of renal hemodynamics will provide greater opportunities for the progression of CRRT hemodynamic therapy.</p>
Subject(s)
Animals , Female , Humans , Male , Acute Kidney Injury , Therapeutics , Hemodynamics , Physiology , Renal Dialysis , Methods , Renal Replacement Therapy , MethodsABSTRACT
<p><b>BACKGROUND</b>Septic cardiomyopathy is a common finding in septic shock patients. The accepted definition of septic cardiomyopathy is often based on the left ventricular ejection fraction (LVEF). The aim of this study was to determine whether the left ventricular longitudinal systolic function was more sensitive than the LVEF in heart function appraisal of septic shock patients.</p><p><b>METHODS</b>This was a case-control study conducted at a 40-bed Intensive Care Unit (ICU) of Peking Union Medical College Hospital. Septic shock patients admitted to the ICU were consecutively enrolled in the study group from March 1, 2016 to September 1, 2016. The control group was selected from nonsepsis patients who were admitted to the ICU and were comparable to the study group. Transthoracic echocardiography was performed to obtain the LVEF measurement, mitral annular plane systolic excursion (MAPSE), tissue Doppler velocity measurement of mitral annulus (Sa), and tricuspid annular plane systolic excursion.</p><p><b>RESULTS</b>The study group consisted of 45 septic shock patients. Another 45 nonsepsis patients were selected as the control group. There was no difference in the LVEF between the two groups (64.6% vs. 67.2%, t= -1.426, P= 0.161). MAPSE in the study group was much lower than in the control group (1.2 cm vs. 1.5 cm, t= -4.945, P< 0.001). Sa in the study group was also lower than in the control group (10.2 cm/s vs. 11.8 cm/s, t = -2.796, P= 0.014).</p><p><b>CONCLUSIONS</b>Compared to the LVEF, longitudinal systolic function might be more sensitive in the detection of cardiac depression in septic shock patients. In the heart function appraisal of septic shock patients with a normal ejection fraction, more attention should be given to longitudinal function parameters such as MAPSE and Sa.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Cardiomyopathies , Pathology , Case-Control Studies , Echocardiography , Echocardiography, Doppler , Hemodynamics , Physiology , Intensive Care Units , Shock, Septic , Pathology , Ventricular Function, Left , PhysiologyABSTRACT
Objective To investigate the respiratory and cardiac characteristics of elderly Intensive Care Unit (ICU) patients.Methods Twelve senior ICU patients aged 90 years and older were enrolled in this study. We retrospectively collected all patients' clinical data through medical record review. The basic demographics, primary cause for admission, the condition of respiratory and circulatory support, as well as prognosis were recorded. Shock patients and pneumonia patients were specifically analyzed in terms of clinical manifestations, laboratory variables, echocardiography, and lung ultrasound Results.Results The mean age of the included patients was 95 years with a male predominance (8 to 4, 66.7%). Regarding the reasons for admission, 6 (50.0%) patients had respiratory failure, 1 (8.3%) patient had shock, while 5 (41.7%) patients had both respiratory failure and shock. Of the 6 patients who suffered from shock, only 1 was diagnosed with distributive shock, 5 with cardiogenic shock. Of the 5 cardiogenic shock patients, 1 was diagnosed with acute coronary syndrome. The rest 4 cardiogenic shock patients were diagnosed with Takotsubo cardiomyopathy. The patient with ST-segment elevation myocardial infarction died within 24 hours. Of the 4 Takotsubo patients, 1 died on day-6 and the other 3 patients were transferred to ward after heart function recovered in 1 to 2 weeks. Of the 10 pneumonia patients, 3 were diagnosed as community acquired pneumonia, and 7 as hospital acquired pneumonia. Only 3 patients were successfully weaned from ventilator. The others required long-term ventilation complicated with heart failure, mostly with diastolic heart failure. Lung ultrasound of 6 patients with diastolic dysfunction showed bilateral B-lines during spontaneous breathing trial.Conclusions Elderly patients in shock tend to develop Takotsubo cardiomyopathy. Diastolic heart dysfunction might be a major contributor to difficult weaning from ventilator in elderly patients. Bedside lung ultrasonography and echocardiography could help decide the actual cause of respiratory failure and shock more accurately and effectively.
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OBJECTIVE: To study the in situ small intestinal absorption mechanism of ZYS-01 in rats and discuss its absorption mechanism. METHODS: Single pass intestinal perfusion model was established, intestinal perfusate concentration of ZYS-01 was measured by HPLC, using the gravimetric method corrected the perfusate volume, absorptions of different dose groups of ZYS-01 in different segments and the effect of P-glycoprotein(P-gp) inhibitors on the absorption of ZYS-01 were investigated. RESULTS: ZYS-01 was absorpted in the whole small intestinal segments, its absorption rate was related to intestinal segments and perfusate concentrations, Peff was more than 0.2×10-4 cm·s-1. P-gp inhibitors could obviously increase the absorption of ZYS-01 in different intestinal segments. CONCLUSION: ZYS-01 is high permeable drug, it can be absorpted in the whole small intestinal segments, duodenum has the fastest absorption rate. the absorption is effected by different concentrations, low concentration has the fastest absorption rate, with the increasing of concentration, the absorption rate decreased gradually. The absorption mechanism of ZYS-01 is active transport. ZYS-01 may be a substrate for P-gp.
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Currently, chemotherapy is one of the main therapy for cancer. But the traditional antitumor drugs are systemic distribution in vivo, they are difficult to achieve an effective drug concentration in the tumor tissue and don't have the ability to distinguish normal cells and tumor cells by themselves, that cause systemic toxicity easily and can not meet the clinical needs. With the research on mesoporous silica nanoparticles (MSNs) deepening, more and more attention in the drug delivery system have been payed to in recent years, because of its unique physicochemical structure characteristics, it has the effect on specific targets, directly inhibits the tumor cell growth, reduces the side effects to normal cells, tissues and organs and can be long-term medication, etc. It is expected to be excellent carriers of antitumor drugs. MSNs application in the field of cancer treatment has now become a hot research field of medicine. In this paper, the latest research about MSNs in antitumor drugs targeting delivery system from 2008 to 2015 is summarized, including the application of MSNs separately in antitumor drug targeting, passive targeting, active targeting, physical or chemical conditions response targeting and other compound targeting drug delivery system. We expect it to provide a reference to the toxicity reducing and efficacy enhancing and further development of chemical medicine, natural medicine and monomeric compound of chinese herbal medicine.
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Animals , Humans , Antineoplastic Agents , Chemistry , Pharmacology , Drug Delivery Systems , Methods , Nanoparticles , Chemistry , Neoplasms , Drug Therapy , Silicon Dioxide , ChemistryABSTRACT
To study the absorptive characteristics of aqueous extracts from Salviae Miltiorrhizae Radix et Rhizoma by in vitro rat everted intestinal sac model. Three representative ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et Rhizome--protocatechuic aldehyde (PAL), posmarinic acid (RA) and salvianolic acid B (SAB), were selected as the study objects. An UPLC method was established to determine and measure their cumulative absorption amount, in order to explain the absorption characteristics of ingredients in different intestinal sections. According to the experimental result, RA and SAB showed the passive absorption in ileum, which conformed to the first-order absorption rate; with low and medium doses, they showed a zero-order absorption rate in jejunum, which was reflected in the coexistence of both positive and passive absorptions; PAL showed a passive absorption manner both in ileum and jejunum. According to the experiment for absorption in different intestinal sections, RA and SAB were mainly absorbed in jejunum, while PAL was absorbed mainly in ileum. All of the three ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et rhizome--PAL, RA and SAB could be absorbed in intestines, but with differences in the absorption rate and mechanism, which indicated that the intestinal absorption of aqueous extracts from Salviae Miltiorrhizae Radix et rhizome was selectivity, instead of a simple semi-permeable membrane penetration process.
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Animals , Male , Rats , Intestinal Absorption , Plant Extracts , Pharmacokinetics , Rats, Sprague-Dawley , Rhizome , Salvia miltiorrhizaABSTRACT
<p><b>OBJECTIVE</b>To study the effect of exogenous Ca2+ on photosynthetic parameters of Pinellia ternate and accumulations of active components under high temperature stress.</p><p><b>METHOD</b>The pigment contents of P. ternata leaves, photosynthesis parameters and chlorophyll fluorescence parameters of P. ternata leaves, the contents of guanosine, adenosine and polysaccharide in P. ternata tubers were measured based on different concentrations of exogenous Ca2+ in heat stress when the plant height of P. ternata was around 10 cm.</p><p><b>RESULT</b>The contents of total chlorophyll and ratio of chlorophyll a/b were relatively higher by spaying Ca2+. Compared with the control, spaying 6 mmol x L(-1) Ca2+ significantly enhanced the net photosynthetic rate (Pn), transpiration (Tr) and stomatal limitation (L8), but reduced intercellular CO2 concentration (C) in P. ternata leaves. With the increase of Ca2+ concentration, maximal PS II efficiency (Fv/Fm), actual photosynthetic efficiency (Yield) and photochemical quenching coefficient (qP) initially increased and then decreased, however, minimal fluorescence (Fo) and non-photochemical quenching coefficient (NPQ) went down first and then went up. The contents of guanosine and polysaccharide and dry weight of P. ternata tubers showed a tendency of increase after decrease, and the content of adenosine increased with the increase of Ca2+ concentration. The content of guanosine and polysaccharide in P. ternata tubers and its dry weight reached maximum when spaying 6 mmol x L(-1) Ca2+.</p><p><b>CONCLUSION</b>With the treatment of calcium ion, the inhibition of photosynthesis and the damage of PS II system were relieved in heat stress, which increased the production of P. ternata tubers.</p>
Subject(s)
Breeding , Calcium , Pharmacology , Chlorophyll , Metabolism , Dose-Response Relationship, Drug , Heat-Shock Response , Organ Size , Photosynthesis , Pinellia , Metabolism , Physiology , Plant Leaves , MetabolismABSTRACT
IN the presence of septic shock, every hour in delaying the administration of effective antibiotics is associated with a measurable increase in mortality. This is especially true for neutropenic patients with septic shock.1 As there is a higher incidence of involving multi-drug resistant pathogens for neutropenic patients, the decision on antibiotics regime remains a challenge for physicians.2 Immunosuppression and previous antibacterial use are factors that promote the spread of multi-drug resistant pathogens, and the possibility of co-existing multi-drug resistant pathogens should be suspected when treating patients with these risk factors who developed refractory shock. Here we present a case with neutropenic fever and refractory shock whose blood culture yielded multi-drug resistant Acinetobacter baumannii and carbapenem- resistant Klebsiella pneumoniae.