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BACKGROUND@#Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity.@*METHODS@#First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells.@*RESULTS@#A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC.@*CONCLUSIONS@#A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
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Humans , Mice , Animals , Psilocybin/metabolism , Fear , Extinction, Psychological , Brain-Derived Neurotrophic Factor/metabolism , Bromodeoxyuridine/pharmacology , Hippocampus/metabolism , Neuronal Plasticity , TOR Serine-Threonine Kinases/metabolismABSTRACT
Postoperative surgical site infection (SSI) can lead to adverse clinical outcomes in patients, such as prolonged hospital stay, increased medical costs, and severe economic burden on patients and on society.In addition, it may also cause nosocomial cross-infection.Therefore, it has aroused the high attention of medical workers.The development of SSI is closely related to a variety of factors, including patient factors, such as blood glucose levels, smoking, systemic use of steroids, obesity and malnutrition, and perioperative related factors, such as long preoperative hospital stay, preoperative skin preparation and prophylactic use of antibiotics of patients, hand hygiene and asepsis principles of medical staff, operation-related factors, anesthetic management and operation related factors, operating room environment factors and postoperative factors.Through reading a large number of relevant literatures published in recent years and according to the work characteristics of anesthesiologists, the author summarized the influential factors and preventive measures for postoperative SSI for the reference of fellow doctors.
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The coronavirus disease 2019(COVTD-19)epidemic has caused wide concern all over the world, including China. In order to fight against epidemic situation, the professional knowledge and practice of anesthesiologists in standard prevention, disinfection and isolation, hand hygiene, environmental sanitation, aseptic operation, occupational protection and other aspects of infection control need to be improved and standardized. Aiming at solving the main problems existing in anesthesia-related infection control in China, we put forward the following suggestions after considering COVID-19 epidemic situation deeply and sorting out the relevant laws, regulations and normative requirements.(1) In terms of standard prevention, during the diagnosis and treatment of suspected or confirmed COVID-19 patients, anesthesia practioners should wear protective equipment according to the tertiary protective measures, including wearing N95 medical respirator, goggles or protective screen, wearing protective clothing, etc.(2) In terms of hand hygiene, hand washing or hand sanitization should be carried out in strict accordance with the hand hygiene regulations when anesthetizing confirmed or suspected COVID-19 cases. Double gloves are essential, after contact with the patient, remove and discard the outer gloves if you need to touch the anesthetic machine or other areas.(3) In terms of environmental sanitation, anesthesiologists should promptly clean and disinfect small areas of patients′ blood and other contamination when performing operations for suspected or confirmed COVID-19 cases. After the operation, the person in charge of infection control in the operating room should strictly implement the technical specification for disinfection of medical institutions, clean and disinfect the operating room (air, object surface, ground, etc.), medical instruments, and objects used by patients, especially the surfaces frequently touched by anesthesiologists.(4) In terms of anesthesia machine disinfection, it is recommended to combine the use of anesthesia internal circuit disinfection machine with the use of artificial nose at the expiratory end and inspiratory end. High efficiency and low capacity hydrophobic filter are preferred in order to make bacteria and virus clearance rate>99.999%. The respiratory pathway filter should be replaced every 3-4 h. (5) In term of isolation, confirmed or suspected COVID-19 cases should be operated in the negative pressure operating room. Medical personnel should inform laminar flow engineering technical personnel to check in time, when necessary to replace the hepa filter for negative pressure operating room.(6) In other aspects, when anesthesia is performed for COVID-19 patients, sharp instruments in anesthesia operation should be carefully handled to prevent stabbing. Latrogenic occupational exposure treatment process should be initiated immediately after stabbing occurs.
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Objective To investigate the effects of special anticoagulation method of hybrid coronary revascularization procedure on postoperative bleeding and clinical outcomes.Methods One hundred and forty-one ASA Ⅱ or Ⅲ consecutive patients,aged 35-82 yr,weighing 45-105 kg,undergoing one-stop hybrid coronary revascularization procedure from June 2007 to January 2011 in Fuwai cardiovascular hospital were enrolled and served as Hybrid group.Using propensity score methodology,these patients were matched with another 141 patients who had undergone off-pump coronary artery bypass grafting (OPCAB group) during the same period,selecting from the surgical database.These ASAⅡ or Ⅲ 141 patients,aged 43-80 yr,weighing 47-110 kg,who underwent OPCAB,were served as control subjects.In group Hybrid,the left internal mammary artery was isolated and then 100-120 U/kg heparin was administrated to maintain activated clotting time between 250-300 s,and additional heparin was given if needed.Protamine 1 mg/kg was used to reverse the effect of heparin after anastomosis between left internal mammary artery and left anterior descending branch.Before stent implantation,6000-8000 U heparin and 300 mg clopidogrel were administrated.Activated clotting time was maintained between 200-250 s until the end of operation.Clopidogrel 75 mg/d was taken for at least 12 months after operation.The volume of postoperative chest tube drainage,mechanical ventilation time,length of stay in intensive care unit,postoperative transfusion of allogeneic blood,re-intubation,myocardial damage,acute kidney injury,atelectasis,hydrothorax and thromboembolism were recorded.Results No thromboembolism was observed within the stent during stay in hospital after operation in patients.The volume of chest tube drainage was significantly less,mechanical ventilation time and length of stay in intensive care unit were shorter,the incidence of atelectasis and hydrothorax and transfusion of allogeneic blood requirement were lower in Hybrid group than in OPCAB group (P ＜ 0.05).There was no significant difference in the incidences of re-intubation,myocardio damage,and acute kidney injury between the two groups (P ＞0.05).Conclusion Special anticoagulation method of hybrid coronary revascularization procedure does not increase postoperative bleeding and has a better clinical outcomes during the early period.
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Objective To evaluate premature clopidogrel cessation,intraoperative tranexamic acid and their interaction on bleeding and transfusion outcomes in on-pump CABG patients.Methods The current study is a prospective and randomized trial with 2 × 2 factorial design.The first factor is preoperative clopidogrel with 2 levels,clopidogrel ingestion within 7 days preoperatively (group E) and nave to clopidogrel (group B).The second level is antifibrinolytic therapy with 2 level,tranexamic acid (group T) and placebo (group P).A total of 333 patients receiving selective on-pump CABG were recruited.The tranexamic acid regimen was a bolus of 10 mg · kg-1 followed by a maintenance of 10 mg · kg 1 · h-1 throughout the surgery.Results Baseline characteristics were fairly balanced among the groups.Tranexamic acid significantly reduced postoperative blood loss.major bleeding,the volume of erythrocyte and plasma transfused,the exposure of erythrocyte,plasma and any allogeneic products (ET vs EP,P ＜ 0.01 ; BT vs BP,P ＜ 0.01).Clopidogrel within 7 days preoperatively significantly increased blood loss (EP vs BP,P＜0.05),major bleeding,the volume of erythrocyte (EP vs BP,P＜0.01) and the exposure of erythrocyte and plasma (EP vs BP,P ＜ 0.05) and any allogeneic products (EP vs BP,P ＜ 0.01).Under the protection of tranexamic acid,the bleeding and transfusion outcomes were comparable between the patients with premature clopidogrel cessation and those nave to clopidogrel (ET vs BP,P ＞0.05).Perioperative mortality,morbidity and the incidence of adverse events were comparable among the groups except for IABP.Conclusion Comparing with nave to clopidogrel,premature cessation within 7 days preoperatively deteriorated bleeding and transfusion outcomes in on-pump CABG patients.Intraoperative tianexamie acid could reduce the risk.
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Objective To evaluate the blood-saving effect of tranexamic acid in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).Methods The study was a prospective,randomized and placebo-control trial.Two hundred ASA Ⅰ-Ⅳ patients,aged 18-64 yr,weighing 50-100 kg,were randomized to receive placebo (group C,n =100) or tranexamic acid (group T,n =100).Tranexamic acid 10 mg/kg was intravenously infused over 20 min before skin incision followed by continuous infusion at 10 mg· kg-1 · h-1 until the end of operation in group T.While the equal volume of normal saline was given in group C.The total volume of postoperative chest tube drainage,postoperative massive bleeding and a second thoracotomy for stopping the bleeding were reordered.The requirement for transfusion of allogeneic blood and complications during the perioperative period were also recorded.Results Compared with group C,the total volume of postoperative chest tube drainage and incidences of postoperative massive bleeding and a second thoracotomy for stopping the bleeding were significantly decreased,and the requirement for transfusion of allogeneic red blood cells,platelet and fresh frozen plasma was reduced in group D (P ＜ 0.05).There was no significant difference in the incidence of complications between the two groups (P ＜ 0.05).Conclusion Tranexamic acid exerts the blood-saving effect in patients undergoing CABG with CPB and can significantly reduce postoperative bleeding and transfusion of allogeneic blood.
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ObjectiveTo investigate the effect of tranexamic acid on inflammatory response in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods Sixty ASA Ⅰ -Ⅲ and NYHA Ⅰ -Ⅲ patients of both sexes,aged 45-64 yr,with body mass index 16-22 kg/m2,undergoing elective OPCABG,were randomly divided into 2 groups ( n =30 each):control group (group C) and tranexamic acid group (group T).Anesthesia was induced with iv injection of midazolam,fentanyl and pipecuronium.The patients were tracheal intubated and mechanically ventilated.PETCO2 was maintained at 35-45 mm Hg.Tranexamic acid 1 g was infused intravenously over 30 min after induction followed by continuous infusion at 400 mg/h until the end of operation in group T.While equal volume of normal saline was given in gtoup C.Anesthesia was maintained with inhalation of isoflurane and intermittent (i)v boluses of fentanyl and pipecuroninm.Venous blood samples were taken before induction,at the end of operation and 24 h after operation for determination of Hb,platelet count,prothrombin time,international normalized ratio and plasma D-dimer and IL-6 concentrations.The volume of chest tube drainage was collected and recorded at 6 and 24 h after operation.The requirement for transfusion of allogeneic red blood cells and fresh frozen plasma was recorded.The complications during hospital stay were also recorded.ResultsCompared with group C,the plasma concentrations of D-dimer and IL-6 were significantly decreased at the end of operation and 24 h after operation,and the volume of chest tube drainage and the requirement for transfusion of allogeneic red blood cells and fresh frozen plasma were significantly decreased after operation in group T ( P ＜ 0.05 or 0.01).There was no significant difference in Hb,platelet count,prothrombin time and international normalized ratio between the two groups (P ＞ 0.05).No complications occurred during hospital stay in the two groups.ConclusionTranexamic acid can reduce inflammatory response in patients undergoing OPCABG.
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Objective To investigate the blood-saving effect of tranexamic acid in off-pump coronary artery bypass (OPCAB). Methods Two hundred and sixty ASA Ⅰ- Ⅲ and NYHA Ⅰ- Ⅲ patients of both sexes,aged 18-64 yr, with body mass index 16-22 kg/m2 , undergoing OPCAB, were randomly divided into 2 groups (n = 130 each): control group (group C) and tranexamic acid group (group T) . Anesthesia was induced with iv injection of midazolam 0.1 mg/kg, fentanyl 5-10μg/kg and pipecuronium 0.1 mg/kg. The patients were tracheal intubated and mechanically ventilated. PEr CO2 was maintained at 35-45 mm Hg. A bolus of tranexamic acid 1 g was infused intravenously within 30 min after indution followed by continuous infusion at 400 mg/h until the end of operation in group T. While equal volume of normal saline was given in control group. Anesthesia was maintained with inhalation of isoflurane and intermittent iv injection of fentanyl and pipecuronium. Venous blood samples were taken before induction, at the end of operation and at 24 h after operation for determination of Hb, platelet count (P1t), prothrombin time (PT) and international normalized ratio (INR). The volume of chest tube drainage was collected and recorded at 6 and 24 h after operation. The requirement for transfusion of allogeneic red blood cells and fresh frozen plasma was also recorded. Results There was no significant difference in Hb, Plt, PTand INR at each time point between the two groups ( P ＞ 0.05). The requirement for transfusion of allogeneic red blood cells and fresh frozen plasma was significantly reduced in group T as compared with group C ( P ＜ 0.05 or 0.01 ). No deaths and complications occurred during hospital stay in the two groups. Conclusion Tranexamic acid exerts the blood-saving effect in OPCAB.
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Objective To investigate the effects of intraoperative intravenous ulinastatin infusion on perioperative lung function in patients undergoing off-pump coronary artery bypass grafting (OPCABG). Methods Twenty-four NYHA class Ⅰor Ⅱ patients aged 65-75 y undergoing elective OPCABG were randomly divided into 2 groups(n=12 each): control group (C) and ulinastatin group (U). In group U, after tracheal intubation the patients received iv injection of ulinastatin 6 000 U/kg over 30 min followed by iv ulinastatin infusion at 1 000 U·kg-·h-1 until the end of surgery. In group C equal vohtme of normal saline was administered iv instead of ulinastatin. Radial artery and right internal jugular vein were cannulated for BP and CVP monitoring and blood sampling. The patients were premeditated with intramuscular morphine 10 mg. Anesthesia was induced with midazolam 0.1 mg/kg, fentanyl 10 μg/kg and pipecuronium 0.1 mg/kg and maintained with 1%-2% sevoflurane in 70% O2 and intermittent iv boluses of fentanyl and pipecuronium. Blood samples were taken before (T1) and at the end of operation (T2) and at 4, 8, 20 h after operation (T3.5) for determination of plasma CD11/CD18 expression, plasma IL-6 and serum NO concentrations, and blood gases. P(A-a) O2 and respiratory index (RI) (RI=P(A-a)O2/PaO2) were calculated. Mechamcal ventilation time in ICU was recorded. Results The two groups were comparable with respect to age, sex, body weight, duration of anesthesia and surgery, and the number of bypass grafts. The plasma level of IL-6, and expression of CD11 b/CDI8 were significantly increased while serum NO level was significantly decreased after operation as compared to the baseline values before operation (T1) in group C. There was no significant change in the plasma levels of IL-6, CD11b/CDI8 expression and serum levels of NO after operation in group U. P(A-a)O2 and RI were significantly increased after operation in both groups and were significandy lower in group U than in group C. The mechanical ventilation time in ICU was significantly shorter in group U than in group C. Conclusion Intravenous ulinastatin inihsion can significantly protect lung function during OPCABG by inhibiting inflammatory response.
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Objective To determine the risk factom for the development of systemic inflammatory response syndrome(SIRS)in patmnts after off-pump coronary artery bypass grafting(OPCABG).Methods Sixty NYHA Ⅰ or Ⅱ patients,aged 46-73 yr,weighing 54-110 kg,undergoing OPCABG,were studied.Blood samples from intemal iugular vein were taken for determination of the plasma concentrations of IL-6 and IL-10 at 4 h after the surgery by ELISA.SIRS 8COre W88 performed during 24 h after the surgery.The patients were divided into 2 groups:SIRS group(S,SIRS 8core≥2)and non-SIRS group(U,SIRS score<2).Factors including age,sex,weight,percentage of mononuclear cells,concentration of hemoglobin,time of operation,left ventricular ejection firction,whether using proteinase inhibitor or not during surgery and plasma concentrations of IL-6 and IL-10 at 4 h after surgery were reccorded.The risk factors were identified by logistic regression analysis.Results Logistic analysis indicated that percentage of mononuclear cells,concentration of hemoglobin,the plasma concentrations of IL-6 and IL-10 were closely related with the development of SIRS in patients after 0PCABG(P<0.05),Y=0.155+0.52 X1+0.39 X2+0.76X1-0.79X,Conclusion The percentage of mononuclear cells,concentration of hemoglobin,and plasma concentrations of IL-6 and IL-10 after surgery Call be the risk factors for the development of SIRS in patients after OPCABG.
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Objective To investigate the effects of different doses of ulinastatin on platelet counts and function after normothermic cardiopulmonary bypass (CPB) in rabbits. Methods Fifty lung-ear white rabbits aged 5-6 months weighing 2.3-3.0 kg were randomly assigned to one of 5 groups (n = 10 each) : control group (group C) and4 ulinastatin groups (group U~1, U_2,U_3,U_4). The rabbits received ulinastatin 1×10~4, 3×10~4, 5×10~4 and 10×10~4 U/kg before CPB in group U~1, U_2, U_3 and U_4 respectively while equal volume of normal saline was given instead of ulinastatin in group C. All rabbits underwent CPB for 30 min at perfusion flow of 72-120 ml·kg~(-1) ·min~(-1). The rectal temperature was maintained at 36.5-37.5℃. Hemodynamic parameters were recorded and blood platelet count, platelet adhesion rate and platelet membrane glycopretein Gp Ⅰ b, Gp Ⅱ b, Gp Ⅲ a receptors were determined before CPB (baseline), at termination of CPB and at 1, 2 and 3 h after CPB. Results The platelet counts were significantly decreased after CPB in all 5 groups (P< 0.05), but there was no significant difference among the 5 groups. The platelet adhesion rates were significantly decreased after CPB as compared with the baseline value before CPB in all 5 groups but the platelet adhesion rates were significantly higher after CPB in group U_4 than in group C. The number of molecules of Gp Ⅰ b, Gp Ⅱ b and Gp Ⅲ a receptors was significantly decreased after CPB in all 5 groups. The number of molecules of Gp Ⅰ b, Gp Ⅱ b and Gp Ⅲ a receptors after CPB was significantly higher in group U_2, U_3 and U_4 than in group C, and there was no significant difference between group U_3 and U_4 . ConclusionUlinastatin 3×10~4-5×10~4 U/kg administered before CPB can inhibit breakdown of platelet membrane glycoprotein receptors. Ulinastatin 10×10~4 U/kg can preserve the platelet adhesion function.