Effects of propofol on desipramine-sensitive [3H]-noradrenaline uptake kinetics in rat femoral artery

BACKGROUND: The intravenous anaesthetic propofol inhibits the neuronal uptake of noradrenaline (uptake1) from the vascular sympathetic neuromuscular junction, resulting in an enhancement of the sympathetic neurotransmission. This could be important for maintenance of blood pressure during propofol anaesthesia. The aim of the present study was to determine how propofol influences the kinetics of uptake1. METHODS: Isolated segments of rat femoral arteries were incubated with [3H]-noradrenaline in the presence or absence of propofol and the radioactivity taken up was measured in a scintillation counter. The uptake1 inhibitor, desipramine, was used to delineate the specific neuronal uptake. RESULTS: Desipramine and 10 microM propofol significantly reduced the uptake in segments incubated with 0.1 microM [3H]-noradrenaline. Propofol at 1 microM and 100 microM did not affect the uptake. Non-linear regression analysis of specific uptake yielded Km 0.50 microM, Vmax 1.6 pmol mg(-1) 15 min(-1) and Hill coefficient 1.1. Propofol (1-10 microM) increased the Km value and propofol (10-100 microM) increased the Vmax value concentration-dependently, while the Hill coefficient was not affected. CONCLUSION: Propofol seems to have a biphasic effect on the uptake of noradrenaline in the vascular sympathetic neuromuscular junction. At lower propofol concentrations there is a decrease in the affinity of the noradrenaline transporters. The resulting uptake inhibition is counteracted at higher propofol concentrations by an increase in the efficacy of the uptake.     

Severe neuroexcitatory symptoms after anaesthesia--with focus on propofol anaesthesia

Delayed neuroexcitatory symptoms after an uneventful anaesthesia are uncommon, although described in many reports. We want to report on two cases. The first patient developed muscle hypertonicity, jerky movements and unconsciousness after an uneventful anaesthesia with propofol, and later the same thing happened after anaesthesia with thiopentone. The second patient developed similar symptoms after an uneventful anaesthesia with propofol, but she never recovered completely after this and is now severely disabled. A search of the literature and the Swedish adverse drug reactions register revealed many similar cases. In both our patients the causal relationship between propofol and the neuroexcitatory symptoms remains uncertain, but we want to alert readers about this possible adverse reaction.     

丙泊酚、芬太尼对妇科腹腔镜手术气腹时SNAP指数和血流动力学的影响

目的研究妇科腹腔镜手术气腹时的心血管反应和脑电双频指数(SNAP指数)变化关系以及丙泊酚、芬太尼对它的影响。方法ASAⅠ或Ⅱ级妇科腹腔镜手术病人80例,随机分芬太尼(F)组、丙泊酚(P)组、芬太尼-丙泊酚(FP)组和对照(C)组,C组不做处理,其他三组分别在气腹前5min静脉注射芬太尼、丙泊酚或芬太尼 丙泊酚。以咪唑安定、芬太尼、维库溴铵、丙泊酚顺序静脉注射麻醉诱导,然后异氟醚维持麻醉。气腹前5min按照分组静脉注射相应药物。结果气腹后C组和F组的SNAP指数、SBP、HR显著升高(P<0.01),FP组的SNAP指数显著降低(P<0.01)。气腹前后,C组、F组之间以及P组、FP组之间SNAP指数、SBP、HR的差异无统计学意义。拔管时间,C组明显短于其他三组(P<0.01),FP组明显长于F组和P组(P<0.05)。结论SNAP指数能有效监测妇科腹腔镜手术时的CO2气腹反应。丙泊酚或者芬太尼-丙泊酚可以有效抑制气腹反应,但使用丙泊酚 芬太尼会使患者苏醒延迟。     

Comparison of the effects of dexmedetomidine and propofol on hypothermia in patients under spinal anesthesia: a prospective,randomized, and controlled trial

Background: Redistribution hypothermia caused by vasodilation during anesthesia is the primary cause of perioperative hypothermia. Propofol exerts a dose-dependent vasodilatory effect, whereas dexmedetomidine induces peripheral vasoconstriction at high plasma concentrations. This study compared the effects of dexmedetomidine and propofol on core temperature in patients undergoing surgery under spinal anesthesia.Methods: This prospective study included 40 patients (aged 19-70 years) with American Society of Anesthesiologists Physical Status class I-III who underwent elective orthopedic lower-limb surgery under spinal anesthesia. Patients were randomly allocated to a dexmedetomidine or propofol group (n = 20 per group). After induction of spinal anesthesia, patients received dexmedetomidine (loading dose: 1 μg/kg over 10 min; maintenance dose: 0.2-0.7 μg/kg/h) or propofol (loading dose: 75 μg/kg over 10 min; maintenance dose: 12.5-75 μg/kg/min). The doses of sedatives were titrated to maintain moderate sedation. During the perioperative period, tympanic temperatures, thermal comfort score, and shivering grade were recorded.Results: Core temperature at the end of surgery did not differ significantly between the groups (36.4 ± 0.4 and 36.1 ± 0.7°C in the dexmedetomidine and propofol groups, respectively; P = 0.118). The lowest perioperative temperature, incidence and severity of perioperative hypothermia, thermal comfort score, and shivering grade did not differ significantly between the groups (all P > 0.05).Conclusions: In patients undergoing spinal anesthesia with moderate sedation, the effect of dexmedetomidine on patients'' core temperature was similar to that of propofol.     

General anesthetics selectively modulate glutamatergic and dopaminergic signaling via site-specific phosphorylation in vivo

Isoflurane, propofol and ketamine are representative general anesthetics with distinct molecular mechanisms of action that have neuroprotective properties in models of excitotoxic ischemic damage. We characterized the effects of these agents on neuronal glutamate and dopamine signaling by profiling drug-induced changes in brain intracellular protein phosphorylation in vivo to test the hypothesis that they affect common downstream effectors. Anesthetic-treated and control mice were killed instantly by focused microwave irradiation, frontal cortex and striatum were removed, and the phosphorylation profile of specific neuronal signaling proteins was analyzed by immunoblotting with a panel of phospho-specific antibodies. At anesthetic doses that produced loss of righting reflex, isoflurane, propofol, and ketamine all reduced phosphorylation of the activating residue T183 of ERK2 (but not of ERK1); S897 of the NR1 NMDA receptor subunit; and S831 (but not S845) of the GluR1 AMPA receptor subunit in cerebral cortex. At sub-anesthetic doses, these drugs only reduced phosphorylation of ERK2. Isoflurane and ketamine also reduced phosphorylation of spinophilin at S94, but oppositely regulated phosphorylation of presynaptic (tyrosine hydroxylase) and postsynaptic (DARPP-32) markers of dopaminergic neurotransmission in striatum. These data reveal both shared and agent-specific actions of CNS depressant drugs on critical intracellular protein phosphorylation signaling pathways that integrate multiple second messenger systems. Reduced phosphorylation of ionotropic glutamate receptors by all three anesthetics indicates depression of normal glutamatergic synaptic transmission and reduced potential excitotoxicity. This novel approach indicates a role for phosphorylation-mediated down-regulation of glutamatergic synaptic transmission by general anesthetics and identifies specific in vivo targets for focused evaluation of anesthetic mechanisms.     

地氟醚与丙泊酚的不同配伍对单肺通气时肺内分流的影响

目的探讨地氟醚与丙泊酚的不同配伍在食管癌根治术单肺通气(One lung ventilation,OLV)期间对肺内分流的影响。方法选择择期行食管癌左侧开胸切除术患者45例,ASAⅠ～Ⅱ级,随机均分为3组(每组15例):丙泊酚组(P组)、地氟醚-丙泊酚组(DP组)和地氟醚组(D组),分别于平卧位双肺通气15min(T0),右侧卧位双肺通气15 min(T1),单肺通气15 min(T2)、30 min(T3)、60 min(T4)、90 min(T5)进行动脉血及混合静脉血血气分析,计算肺内分流率(Qs/Qt)。结果 TLV(T0)时,Qs/Qt组间比较,差异无统计学意义(P>0.05);OLV期间(T2～T5)Qs/Qt与TLV(T0)时相比,有明显增高(P<0.05),且D组明显高于P组和DP组(P<0.05),P组与DP组相比,差异无统计学意义(P>0.05)。三组OLV各时的PaO2较TLV时下降(P<0.05),但仍在安全范围内。结论临床剂量[3 mg/(kg.h)]丙泊酚复合低浓度地氟醚(<0.83MAC)对OLV的患者更安全有效。     

丙泊酚用于精神病患者人工通气镇静治疗的临床效果评价

目的研究丙泊酚对精神病患者人工通气在治疗慢性阻塞性肺疾病（COPD）伴重度高碳酸性呼吸衰竭的镇静效果。方法将44例COPD伴重度高碳酸性呼吸衰竭的精神病患者按入院顺序完全随机分为2组各22例,对照组：咪唑安定静脉注射10—20mg;丙泊酚组：丙泊酚静脉注射泵持续输注0．5～2．0mg/（kg·h）,比较治疗0．5、1h后,2组动脉血气分析中的pH值、氧分压（PaO2）、二氧化碳分压（PaCO2）变化,峰值气道压力（Pmax）、平台压（Ppalt）以及肺功能中第1秒用力呼气量与用力肺活量的比值（FEV1／FVC）和呼气峰流速（PEF）的变化。结果丙泊酚组的镇静效果显著优于对照组;与对照组比较,丙泊酚组在治疗后PaCO2显著降低,pH值在治疗后0．5h回到正常范围内,恢复较迅速（P〈0．05或P〈0．01）;治疗后0．5h的PaO2、PaO2／FiO2也比对照组明显升高。丙泊酚组在治疗后的Pmax、Ppalt较对照组有明显下降,PEF、FEV1／FVC的提高较对照组显著,差异有统计学意义（P〈0．05或P〈0．01）。结论丙泊酚进行镇静在COPD伴重度高碳酸性呼吸衰竭治疗中可降低气道阻力,改善氧合功能,减少精神病患者的人机对抗。     

丙泊酚与咪达唑仑对治疗难治性癫痫持续状态的临床观察研究

目的：探讨单用丙泊酚、单用咪达唑仑和2者联用在难治性癫痫持续状态治疗中的疗效、不良反应等,以寻找较好的抗癫痫治疗方案。方法回顾性分析难治性癫痫持续患者75例。使用丙泊酚治疗的患者25例,使用咪达唑仑的患者25例,2药联合使用的患者25例。记录用药前、控制癫痫发作后、停药时这3个时点的心率（HR）、自主呼吸频率（RR）、收缩压（SBP）、舒张压（DBP）、血氧饱和度（SpO 2）以及治疗后镇静评级分数,癫痫控制起效时间以及不良反应的发生情况。结果联合用药组总体有效率为92.0%,显著高于丙泊酚组和咪达唑仑组的80.0%和84.0%（P<0.05）。3组患者用药前HR、RR、SBP、DBP、SpO 2与控制癫痫发作后、停药时所测得值相比,差异有统计学意义（P<0.05）;联合用药后,药物使用总量分别低于单独使用的组别,癫痫控制时间缩短,镇静分数提高（P<0.05）。结论丙泊酚及咪达唑仑2者联合抗癫痫的疗效优于单独使用。     

右美托咪定和丙泊酚用于神经外科躁动患者镇静的比较研 究简

目的 评价神经外科躁动患者应用右美托咪定和丙泊酚镇静治疗的效果及不良反应.方法 选择2010年3月～2011年3月入住武汉大学人民医院ICU中的神经外科急重症及术后躁动患者60例,随机分为两组,右美托咪定组（D组）和丙泊白酚组（P组）,监测给药前（T1）及给药后10 min（T2）、1 h（T3）、2 h（T4）、6 h（T5）和次日清晨7：00（T6）的平均动脉压、心率、呼吸频率、脉搏血氧饱和度,记录药物起效时间、达到Ramsay镇静评分2～4级时药物平均输注速度.结果 两组药物起效时间比较差异有高度统计学意义（P＜0.01）,D组患者用药后血压及心率均有所下降（P＜0.05）,用药后呼吸频率与T1相比虽有所下降,但差异无统计学意义（P＞0.05）;P组镇静治疗后血压较给药前下降,差异有统计学意义（P＜0.05）,与T1比较,T2～4的心率明显下降（P＜0.05）,用药后10 min内即观察到呼吸频率下降,T2与T1相比差异有统计学意义（P＜0.05）.结论 右美托咪定和丙泊酚微量泵持续输入用于神经外科躁动患者镇静安全有效,丙泊酚可应用于躁动患者的快速镇静,右美托咪定镇静过程中无明显呼吸抑制发生,但要注意防范血压下降和心率减慢的不良反应.     

瑞芬太尼联合丙泊酚在关节脱位手法复位麻醉中的应用

目的 观察和分析瑞芬太尼联合丙泊酚用于关节脱位手法复位的临床效果.方法 选取安顺市人民医院2012年7月至2014年7月收治的关节脱位患者62例作为研究对象,随机分为丙泊酚麻醉组(A组)和瑞芬太尼联合丙泊酚麻醉组(B组),各31例.对两组的麻醉效果、不良反应、麻醉起效时间及苏醒时间进行分析.结果 A组麻醉有效率为83.87％,B组为96.77％,差异具有统计学意义(P＜0.05);A组不良反应发生率为41.93％,B组为16.13％,差异具有统计学意义(P＜0.05);B组麻醉起效时间及苏醒时间明显比A组短(P＜0.05),差异具有统计学意义(P＜0.05).结论 瑞芬太尼联合丙泊酚麻醉用于关节脱位手法复位的麻醉效果较好,不良反应发生率低.