目的 建立超高效液相色谱-串联质谱法(UPLC-MS/MS)测定人血浆中苯磺酸顺阿曲库铵的含量,并应用于临床治疗中监测老年患者手术后血浆中的药物残留.方法 样品经含0.1％甲酸的乙腈溶液蛋白沉淀处理后,采用SHISEIDO(资生堂)ADME(3.0 mm×100 mm,2.7μm)色谱柱,流动相以含0.1％甲酸的2 mmol/L乙酸铵溶液和乙腈溶液(30:70,V/V),等度洗脱.质谱检测选择AJS-ESI离子源正离子模式,多反应监测(MRM)检测离子对为:苯磺酸顺阿曲库铵464.3→358.2(m/z)、维库溴铵(IS)557.4→356.3(m/z).收集老年脊柱手术患者麻醉诱导后、手术结束、术后0.5 h、术后1 h以及自体血回输时刻血袋内的血浆样品,于事先加入2％甲酸水溶液的冻存管中保存,测定样本中的苯磺酸顺阿曲库铵的含量,评估自体血回输对老年患者术后血浆苯磺酸顺阿曲库铵浓度的影响.结果 人血浆中苯磺酸顺阿曲库铵在20～5000 ng/ml范围内线性良好,r=0.9997;批内和批间的精密度RSD<10％、准确度RE

AIM: To investigate the changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute normovolemic hemodiluti-on and its influence on the depth of anesthesia, muscle relaxant effect and blood drug concentration after reinfusion. METHODS: Forty patients of both sexes, aged 20-60 yr, American Society of Anesthesiologists physical status Ⅰ or Ⅱ,hemoglobin（Hb） ＞120 g/L, hematocrit（Hct） ＞35%,undergoing eletive multilevel spinal surgery were included, were divided into 2 groups（n=20 each）using a random number table. ANH group（group A）: ANH was performed after stable induction of anesthesia, the target Hct value was 28%-30%, and autologous blood was reinfused after the main operation steps. Control group（group C）: routine transfusion and infusion treatment. The bispectral index（BIS） and Train-of-Four stimulation（TOF）were observed and recorded at the stable induction of anesthesia（T1）, 30 minutes of stable induction（T2）, the end of operation（T3）, 30 minutes after the end of the operation（T4）, 1 hour after the end of the operation（T5） and 2 hours after the end of the operation（T6）. The concentrations of propofol and cisatracurium besylate in plasma at T1-T6,stored blood at 1 h（TS1）, 2 h（TS2）, and before reinfusion（TS3） were detected by Liquid Chromatographytandem Mass Spectrometry. The extubation time and recovery score at T4-6hours were recorded. RESULTS: There was no significant difference in propofol between the two groups at each time point（P ＞0.05）. The plasma concentration of cisatracurium besylate in group A was higher than that in group C at T3（P＜0.05）. The concentration of two kinds of anesthetic drugs in blood samples decreased slightly with time,but there was no significant difference between groups（P＞0.05）. The BIS value at T4and TOF value at T3in group A were significantly lower than those in group C. The recovery score of group A was lower than that of group C at T4（P＜0.05）.There was no significant difference in extubation time（P＞0.05）. CONCLUSION: The plasma concentrations of propofol and cisatracurium besylate were basically unchanged during the in vitro isolation of ANH autologous blood. The plasma concentrations of cisatracurium besylate were only temporarily affected after the main operation steps, but the postoperative muscle relaxation recovery and recovery quality were not significantly affected.

经皮肾镜取石术(Percutaneous Nephrolithoto-my,PCNL),具有清除结石率高、手术时间短等优点,目前已成为治疗肾结石的首选方案.手术操作的关键步骤是建立安全高效的操作通道,可降低手术并发症的发生率.现本文结合最新文献报道一例术中并发呼吸循环衰竭的PCNL.

Objective:To evaluate the effect of intraoperative cell salvage (ICS) on the number and viability of cancer cells in salvaged autologous blood from the patients undergoing liver cancer surgery.Methods:Twenty patients undergoing open radical primary hepatocellular carcinoma were selected, and blood from the operative field was collected after exposing the liver and treated with ICS. Blood specimens 20 ml from the surgical field (S 1), blood specimens 20 ml before ICS treatment-leukocyte depletion filter (LDF) filtration (S 2) and blood specimens 20 ml after LDF filtration (S 3) were collected and enriched, of which the blood sample 10 ml was used for cancer cell identification and count by immunofluorescence staining, and the remaining blood sample 10 ml was continuously cultured for 3 weeks, and then cell viability was observed by immunofluorescence method. Results:Hepatocellular carcinoma(HCC) cells were identified in 19 S 1 specimens, 18 S 2 specimens, and 16 S 3 specimens, but there was no significant difference in the detection rate among the three specimens ( P>0.05). Compared with S 1 specimens, HCC cell count was significantly reduced in S 2 and S 3 specimens ( P<0.05). There was no significant difference in the HCC cell count between S 3 specimens and S 2 specimens ( P>0.05). After 3 weeks of culture, the results of light microscopy showed that: hepatocellular carcinoma cell clusters were found in S1 specimens, and no hepatocellular carcinoma cell cluster was found in S 2 and S 3 specimens; the results of fluorescence microscopy showed that: 400 and 14 mixed epithelial-mesenchymal HCC cells and 100 and 21 mesenchymal HCC cells were found in S 1 and S 2 specimens, respectively, while no HCC cells were identified in S 3 specimens, among which HCC cells mainly presented as clusters of hepatocellular carcinoma cells in S 1 specimen, while no clusters of hepatocellular carcinoma cells were found in S 2 and S 3 specimens. Conclusions:After treatment with ICS or ICS-LDF, the number and viability of hepatocellular carcinoma cells in salvaged autologous blood are significantly reduced, and hepatocellular carcinoma cells exist as single cells and fail to develop clusters of hepatocellular carcinoma cells; LDF can reduce the risk of hepatocellular carcinoma cell autotransfusion to a certain extent, although it can not effectively filter out hepatocellular carcinoma cells continuously.

Objective: To investigate the effect of a single sub-anesthetic dose of ketamine on postoperative anxiety, depression, and inflammatory factors in patients with colorectal cancer.Methods: A total of 104 patients undergoing selective colorectal surgery in our hospital from Jan 2015 to Oct 2017 were included and randomly assigned (1:1:1:1) into a 0.1 mg kg−1 ketamine group (K1 group), 0.2 mg kg−1 ketamine group (K2 group), 0.3 mg kg−1 ketamine group (K3 group), or control group (C group). Corresponding doses of ketamine were given intravenously in the K groups (K1, K2, and K3 groups) 5 min before operation, and the same amount of normal saline was given in the C group. The intravenous analgesia program was identical in the four groups. The patients’ emotional reactions (anxiety and depression) were assessed by the Hospital Anxiety and Depression Scale (HAD), the quality of postoperative recovery was evaluated by the Quality of Recovery-40 (QoR-40) questionnaire, and the levels of IL-6, IL-8, and TNF-α in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA) on the day before operation and within 24, 48, and 72 h post-operation respectively. Pain was estimated by the visual analog scale (VAS), and sedation was assessed with Ramsay score 30 min after extubation. The time points of anesthetic end and extubation were recorded. The complications during anesthesia and recovery such as cough and agitation 30 min after extubation were recorded.Results: The anxiety score (HAD-A) and depression score (HAD-D) of the K3 group were significantly lower than those of the C group post-operation (p < 0.05). The QoR-40 score of the K3 group was significantly higher than that of the C group (p < 0.05). The serum levels of IL-6, IL-8, and TNF-α in the K3 group were significantly lower than those in the C group (p < 0.05 and p < 0.01). There were no significant differences in HAD-A, HAD-D, and QoR-40 scores or serum levels of IL-6, IL-8, and TNF-α between the K1 and K2 groups and the C group. There were no significant differences in VAS pain score or Ramsay sedation score among the four groups 30 min after extubation. There were no significant differences in extubation time, postoperative cough, emergence agitation, or delirium among the four groups. Dizziness, nausea, vomiting, diplopia, or other adverse reactions were not found 30 min after extubation.Conclusion: A single sub-anesthetic dose (0.3 mg kg−1) of ketamine can significantly improve the postoperative anxiety and depression of colorectal cancer patients and reduce the levels of IL-6, IL-8, and TNF-α.

目的 观察目标导向液体疗法对老年全髋关节置换手术(THA)患者循环状态、免疫炎性反应和早期认知功能的影响.方法 选择2019年11月～2020年10月在海军军医大学附属公利医院择期行单侧T H A的患者60例,按随机数字法分为限制性液体治疗组(R组)、开放性液体治疗组(L组)和目标导向液体治疗组(G组),每组20例.记录患者麻醉诱导前(T1)、手术开始1 h(T2)、术毕即刻(T3)、出复苏室(PACU)(T4)时的平均动脉压(MAP)和乳酸(Lac)值;于术前1 d(T0),术后1(T5)、3(T6)、7 d(T7)采集静脉血,检测血清中炎症因子及脑损伤相关蛋白浓度,并评估患者认知功能.结果 G组液体总入量及晶、胶体量高于R组,低于L组(P<0.05).T2、T3时,G组患者MAP高于R和L组(P<0.05);T2、T3、T4时,G组患者Lac值低于R和L组(P<0.05);T5、T6、T7时,G组血清中TNF-α、IL-1β、IL-6、S-100β、tau蛋白浓度低于R和L组,MMSE评分高于R和L组(P<0.05).结论 目标导向液体治疗对维持老年全髋关节置换手术患者循环稳定,减轻术后炎性反应和降低发生术后早期认知功能具有更佳的效果.

目的:观察环氧合酶-2(cyclooxygenase-2,COX-2)抑制剂对老年骨科手术患者血浆炎症因子、神经损伤相关因子和抗氧化因子水平的变化以及疼痛和谵妄评分的影响,明确COX-2抑制剂在术后谵妄(postoperative delirium,POD)防治中的作用并探究其可能的作用机制.方法:选取行择期髋关节置换手术的患者80例,随机分为帕瑞昔布钠组(P组,n=40)和对照组(C组,n=40)两组.P组患者分别于麻醉诱导前30 min和术毕各静注帕瑞昔布钠40 mg;C组相同时点静注同等容量的生理盐水.于术前1 d(T0)术前简易智能检测量表(mini-mental state examination,MMSE)评分筛查患者术前认知功能;术前1 d(T0)、术后1 d(T4)、术后3 d(T6)、术后5 d(T7)意识模糊评估法-中文修订版(CAM-CR)量表评分判断POD的发生;术前1 d(T0)、术后12 h(T3)、术后1 d(T4)、术后2 d(T5)视觉模拟评分量表(VAS)评分观测疼痛程度;于麻醉前30 min(T1)、术后1 h(T2)、术后1 d(T4)、术后3 d(T6)经颈内静脉采集中心静脉血,ELISA法测定血浆中炎症因子(IL-6和IL-10)、神经损伤相关因子(S-100β、NSE、BD-NF)以及抗氧化因子(HO-1)的含量.结果:两组患者一般情况、MMSE评分及T1时点炎症因子、神经损伤相关因子、抗氧化因子均无统计学差异(P>0.05);T2和T4时点,P组IL-6、S-100β、NSE均低于C组,IL-10、BDNF、HO-1高于C组(P<0.05);T6时点,P组S-100β、NSE均低于C组,BDNF高于C组(P<0.05),两组IL-6、IL-10、HO-1无统计学差异(P>0.05).两组T0时点VAS和CAM-CR评分无统计学差异(P>0.05);T3、T4、T5时点,P组VAS评分低于C组(P<0.05);T4、T6、T7时点,P组CAM-CR评分低于C组,P组POD发生率低于C组(P<0.05).结论:COX-2抑制剂(帕瑞昔布钠)可减轻老年患者术后疼痛,降低术后血浆中炎症因子和神经损伤相关因子,上调抗氧化水平,降低POD发生率;其降低POD发生的机制可能与其抗炎、镇痛和抗氧化作用有关.

组学技术是通过超高通量定量跟踪标记底物的实验研究方法,从整体角度出发分析人类组织器官功能和代谢的状态.代谢组学定量研究了在外界不同刺激情况下红细胞代谢物的生理和病理变化,不同代谢物的代谢调节通路.本文深入探究红细胞在体外贮存期间氨基酸、铁、一氧化氮、糖和脂质代谢等能量代谢和氧化损伤的变化,扩大了对于代谢贮存损伤机制的理解,明确红细胞代谢物与机体生理、病理变化的相对潜在关系,为个性化体外红细胞贮存如定制添加剂、研发不同的红细胞贮存液提供思路.

Patients with malignant tumour often require massive transfusion. Intraoperative cell salvage(IOCS) was initially limited in cancer surgery by concerns about the possibility of dissemination of tumor cells into circulation. However, as supportive literature concerning IOCS research and application in cancer surgery are increasing, it is necessary to reassess the perioperative application of IOCS in patients with malignancy. This review summarizes the application, risks and value of IOCS during cancer operations.

目的:探讨肝叶切除术中静脉空气栓塞(VAE)的临床特征、可能发生原因和诊断.方法:报道1例VAE患者临床资料并复习相关文献.结果:患者通过术中临床表现及手术情况确诊VAE,并救治成功.结论:VAE是一种凶险并发症,临床上应警惕VAE的发生,并第一时间诊断和抢救,有条件可使用经食管超声心动图(TEE)进行确诊.

由于红细胞没有线粒体,其能量供应完全依赖于葡萄糖酵解,但高血糖状态可使血红蛋白糖化,产生氧化应激对细胞组分造成损伤.本文系统回顾糖尿病状态下红细胞的变化,分析糖尿病对红细胞理化性质及免疫功能的影响,以期为糖尿病患者的临床治疗提供参考.

阿芬太尼是合成的作用于μ阿片受体的芬太尼衍生物,为短效强镇痛药.相比于芬太尼和舒芬太尼等类似的麻醉药,阿芬太尼的效价最低,起效最快,作用时间更短,静注后1.4 min作用达峰,维持时间10～15 min,分布容积小,符合三室模型,经肝脏代谢失活后经尿排出.阿芬太尼作为芬太尼家族较早应用的药物,在镇痛、镇静、抗焦虑、麻醉诱导和维持等方面已得到广泛应用.近年来,阿芬太尼的应用更加倾向于短小操作、日间手术、保留自主呼吸以及门诊诊疗的麻醉.随着国产阿芬太尼近期研制成功,并逐渐开始在麻醉中应用,阿芬太尼有望成为临床镇痛的新选择,但目前其临床应用经验和相关研究十分有限.本文就阿芬太尼的药理作用特点及在国内外的应用进展作一综述,以期为该药的临床合理应用提供参考.

目的 探讨贮存式自体全血和红细胞成分对骨髓造血干细胞衰老相关指标的影响.方法 健康雄性新西兰家兔30只,3～6月龄,体重2.5～3.0 kg.采用随机数表法将其分为五组:对照组(C组)、单纯手术组(S组)、手术采血组(ABS组)、贮存式自体全血输注组(PAB组)和贮存式自体红细胞输注组(PARB)组,每组6只.C组家兔麻醉后,不做任何处理,按时点采集骨髓标本,其余各组均开腹行肝叶切除,ABS组、PAB组和PARB组于术前1周采血贮存,S组和ABS组术中输液补充血容量,PAB组和PARB组术中分别输注贮存的自体全血和自体红细胞.于麻醉诱导后手术前(T1)、术后6 h(T2)和术后24 h(T3)采集骨髓样本测定家兔CD34+细胞百分比、活性氧(ROS)浓度、衰老细胞比例及衰老相关蛋白(p53、p21)的表达情况.结果 与T1时比较,T2、T3时S组、ABS组、PAB组和PARB组的CD34+细胞百分比明显升高,ROS浓度、衰老细胞比例明显降低,T2时ABS组,T2、T3时S组、PAB组和PARB组p53、p21蛋白含量明显降低(P<0.05).与T2时比较,T3时S组、ABS组、PAB组和PARB组的CD34+细胞百分比明显升高,T3时PARB组衰老细胞比例明显降低,T3时ABS组、PAB组和PARB组p53蛋白含量明显升高,T3时ABS组和PAB组p21蛋白含量明显升高(P<0.05).与C组比较,T2、T3时S组,T1—T3时ABS组、PAB组和PARB组的CD34+细胞百分比明显升高,ROS浓度、衰老细胞比例及p53、p21蛋白含量明显降低(P<0.05).与S组比较,T1时ABS组,T1—T3时PAB组和PARB组CD34+细胞百分比明显升高,T1—T3时ABS组、PAB组和PARB组的ROS浓度明显降低,T1、T2时ABS组,T1—T3时PAB组和PARB组衰老细胞比例和p53、p21蛋白含量明显降低(P<0.05).与ABS组比较,T2、T3时PAB组和PARB组的CD34+细胞百分比明显升高,T1—T3时PAB组和PARB组的ROS浓度明显降低,T2、T3时PAB组和PARB组衰老细胞比例和p53、p21蛋白含量明显降低,T1时PARB组p53、p21蛋白含量明显升高(P<0.05).与PAB组比较,T3时PARB组的CD34+细胞百分比明显升高,T2、T3时PARB组的ROS浓度明显降低,T2时PARB组的衰老细胞比例明显降低(P<0.05).结论 贮存式自体输血在一定程度逆转骨髓细胞衰老表型,促进CD34+细胞生成,从造血干细胞的角度而言,采集并输注红细胞成分比全血更加有益.

Objective:To evaluate the relationship between the mechanism of promoting wound healing by modified autologous blood transfusion and metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) in diabetic mice. Methods:Twenty SPF ICR mice, weighing 21-25 g, in which the diabetic model was successfully established, were divided into 2 groups ( n=10 each) using a random number table method: modified preservation group (group I) and ordinary preservation group (group O). Peripheral venous blood samples were collected and stored in the corresponding preservation solution for 7 days.The platelet aggregation rate, blood glucose, serum glycosylated hemoglobin (GHB) and phosphodiesterase (DPG) concentrations and WBC were measured.Autologous blood was transfused back immediately after the wound model was established.The percentage of wound healing area was calculated at 7, 10 and 14 days after autologous blood transfusion.The expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, matrix metalloproteinase-9, β-actin, type Ⅰ collagen (Col Ⅰ), Col Ⅲ protein and mRNA and MALAT1 was determined by Western blot, immunohistochemistry and quantitative real-time polymerase chain reaction respectively, at 14 days after transfusion. Results:Compared with group O, the blood glucose, serum concentrations of GHB and DPG, and WBC were significantly decreased, platelet aggregation rate was increased, the percentage of wound healing area was increased, the positive staining rate of Col Ⅰ and Col Ⅲ was increased, and the expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, matrix metalloproteinase-9, ColⅠ, Col Ⅲ and β-actin protein and mRNA and MALAT1 was up-regulated in group I ( P<0.05). Conclusion:The mechanism by which modified autologous blood transfusion promotes wound healing may be related to up-regulating MALAT1 expression in diabetic mice.

随着血液供需矛盾的日益加剧,减少异体血输注,提高自体输血率,成为现代医学关注的热点.由于老年患者这一特殊群体日渐增多,自体输血在老年患者手术中应用是否安全仍存有争议.为此,本文将近年来老年患者不同手术类型自体输血的应用及一些特殊病例如肿瘤、细菌污染、贫血、高血压及糖尿病等患者的应用进行分析,综合评估自体输血在老年患者手术中的应用价值及风险.

液体治疗是通过补充(或限制)某些液体的输注,维持手术患者组织灌注良好和生命体征稳定的重要环节,术中恰当的补液方案可减少手术患者的应激反应和术后并发症的发生,促进患者术后恢复.接受手术的老年患者由于自身复杂的病理生理改变,对容量调节能力大大下降,术中不恰当的液体输注会使围手术期不良事件的发生风险显著增加,进而影响老年患者的术后转归.目前关于老年患者术中液体方案的选择尚无定论,恰当的术中补液方案不仅需要精准的监测技术对机体容量进行评估,还需要选择合适的液体种类,这些均需未来进行深入研究.

目的:观察急性等容血液稀释(ANH)自体血回输对老年骨科手术患者脑电双谱指数与肌松效应的影响,探究含有麻醉药成分的自体血回输对术后麻醉苏醒质量及安全性的影响.方法:择期骨科手术患者40例,年龄65～75岁,体质量55～80 kg,ASAⅠ ～Ⅱ级,预计术中出血量≥600 mL.患者随机分为2组(n=20):A组为进行ANH组,在麻醉诱导平稳后实施ANH,血细胞比容(Hct)目标值28％～30％;B组为对照组,即术中常规补液,不进行ANH.于术毕回输自体血时(T1)、回输10 min(T2)、20 min(T3)、30 min(T4)、40 min(T5)、50 min(T6)、60 min(T7)各时点观测两组患者脑电双频指数(BIS)、四个成串刺激(TOF值)及丙泊酚、顺式阿曲库铵的血浆药物浓度变化;观察并记录术前(T0)及T7时点血气变化,观察患者拔除气管导管的时间以及苏醒质量.结果:A组BIS值在术后T6、T7时点明显低于B组(P<0.05),A组TOF值在T5、T6、T7时点明显低于B组(P<0.05);A组与B组术后丙泊酚、顺式阿曲库铵的血药浓度组间比较差异无显著性(P>0.05);A组在术后T7时点乳酸(Lac)值明显高于B组(P<0.05);A组拔除气管导管的时间明显长于B组(P<0.05);A组Aldrete评分明显低于B组(P<0.05).结论:ANH后术毕自体血回输可增加血浆中麻醉药物浓度,加深患者的麻醉深度,增强肌松效应,使老年患者呼吸功能恢复和拔管时间延迟.

瑞马唑仑是一种新型超短效镇静药物,具有起效和恢复快,代谢不依赖肝肾功能,呼吸抑制轻,血流动力学稳定,长时间应用无蓄积,羧酸代谢物无药理作用,能被拮抗药氟马西尼快速逆转,有望成为临床镇静药物的新选择.本文就瑞马唑仑的药理学特性和近期的研究进展作一综述,为临床的安全用药提供参考.