可乐定对氯胺酮药效学的影响

用清醒动物研究了可乐定与氯胺酮的相互作用。可乐定可增大氯胺酮引起的小鼠入睡率，延长小鼠睡眠时间，并与氯胺酮的镇痛作用协同。在兔，可乐定将氯胺酮的升压作用翻转为降压，减轻氯胺酮的的呼吸抑制作用。实验结果提示，可乐定可增强氯胺酮的麻醉作网，减轻其不良反应，可乐定与氯胺酮组成复合麻醉是合理的。     

氯胺酮抗炎作用及机制的研究进展

氯胺酮对炎性反应中的炎性因子TNFα、IL-1、6、8均有抑制作用，同时又能增加抗炎因子IL-4、IL-10的表达，减少NO的生成等，从而对感染或非感染时炎性反应造成的组织器官的损害有保护作用，显示了氯胺酮麻醉镇痛作用以外的新用途。     

普鲁卡因氯胺酮静脉复合麻醉对失血性休克犬体循环和冠脉循环血流动力学及心肌代谢的影响

目的与方法：观察失血性休克犬在普鲁卡因、氯胺酮复合静脉麻醉下６０ｍｉｎ内体循环和冠脉循环血流动力学及心肌代谢的变化。结果：除外周血管总阻力下降外,其他体循环及冠脉循环血流动力学指标均无明显的改变。动脉血和冠状窦血乳酸含量增加,心肌乳酸摄取速率和摄取率明显上升。结论：在失血性休克状态下应用普鲁卡因、氯胺酮复合静脉麻醉后心血管功能基本稳定在麻醉前水平,心脏后负荷有所降低,心肌氧供略增,氧耗稍减,保持心肌对乳酸的摄取与其血含量相适应     

右旋氯胺酮的药理学特征及其与阿片类药物联合应用的研究进展

右旋氯胺酮,亦称艾司氯胺酮,是氯胺酮的同分异构体,与氯胺酮相比,具有镇静、镇痛作用更强,呼吸抑制作用小,消除半衰期短,苏醒快的临床优势,使用后患者较少发生精神激动和梦幻等不良反应 [1].临床研究还提示,右旋氯胺酮具有神经保护作用 [2].目前的外科快速康复理念的目标之一就是应用联合镇痛的方法控制围术期疼痛,尽可能减少...     

羟丁酸钠对氯胺酮药效学的影响

用清醒动物研究了羟丁酸钠与氯胺酮的相互作用。羟丁酸钠可增大小鼠静注氯胺酮的ＬＤ５０和氯胺酮引起的小鼠入睡率，延长小鼠睡眠时间，减少躁动，并与氯胺酮的镇痛作用协同。羟丁酸钠对氯胺酮的呼吸、循环效应无明显影响。结果提示，羟丁酸钠可增强氯胺酮的麻醉作用，减轻其不良反应，与氯胺酮组成复合麻醉是合理的。     

急性胆管炎早期Kupffer细胞激活对肝细胞能量代谢的影响

应用枯否氏细胞，肝细胞共同培养Ｒｎ－１２３荧光图像分析技术研究急性胆管炎早期估否氏细胞反应对肝细胞能量代谢的影响，结果表明：大鼠急性胆管炎早期激活的枯否氏细胞对正常肝细胞线粒体能量代谢有明显抑制作用，ＴＮＦ单抗能在一定程度上减轻这种抑制效应，但不能使肝细胞线粒体能量代谢功能完全维持正常。表明急性胆管炎早期肝脏能量代谢障碍与枯否氏细胞的激活有关，ＴＮＦ的过度分泌可能是其中的机制之一。     

罗库溴铵欧洲研讨会综述

罗加溴铵是一种较新的甾类肌松药，它的特点是起效快，体内无蓄积作用，对心血管系统抑制作用弱，对肝，肾功能影响小，对体内代谢及离子平衡影响小，不升同眼压及颅内压，无类过敏反应，静脉麻醉药氯丙嗪，吗啡，硫喷妥钠，氯胺酮对罗库溴铵有增效作用，吸入麻醉药可减少罗库溴铵的用量，延长作用时间，其由强到弱依次为安氟醚，异氟醚，Ｎ２Ｏ。     

静脉麻醉药物对青年和老年人淋巴细胞转化功能的影响

目的评价三种常用麻醉药物对老年人及青年人淋巴细胞转化功能的影响.方法老年组,年龄平均67.3岁;青年组年龄平均25.9岁,每组10人.分别观察不同浓度(0.25、0.50、1.00、2.00ug/ml)的异丙酚、氯胺酮、依托咪酯三种静脉麻醉药物对两组肘静脉血淋巴细胞转化功能的影响.结果1.青年组淋巴细胞在植物血凝素(PHA)刺激下的增殖能力明显高于老年组;2.无论对青年组还是老年组,四个浓度的异丙酚对淋巴细胞转化功能均无明显影响;而氯胺酮和依托咪酯则在高浓度时(大于1ug/m;)能明显抑制淋巴细胞转化功能(P＜0.01),这种抑制作用在两组间比较无显著性差异.结论氯胺酮和依托咪酯对淋巴细胞转化功能有一定的抑制作用,老年组和青年组间差异不明显.     

氯胺酮对颅脑手术患者颅内压的影响

氯胺酮对颅脑手术患者颅内压的影响卢振和１朱建坤２钟钒１神经外科手术患者能否应用氯胺酮存在争议，焦点是氯胺酮可升高ＩＣＰ。为了探讨在神经外科临床应用氯胺酮的安全性，我们在颅内手术病人中观察氯胺酮对颅内压（ＩＣＰ）的影响，现报告如下。资料与方法选择无明显...     

氟哌啶醇对氯胺酮诱导的热休克蛋白70在大鼠海马中表达的影响

目的 研究氟哌啶醇对于氯胺酮诱导的热休克蛋白70（HSP70）在大鼠海马中表达的影响,探讨氟哌啶醇能否预防或治疗氯胺酮导致的脑损害。方法 选择48只大鼠,随机分为8组,分别在腹腔注射氯胺酮80．0mg/kg前后给予不同剂量氟哌啶醇（1．0,5．0,10．0mg/kg),24h后取鼠脑,应用HSP70单克隆抗体免疫组化染色检测大鼠海马中HSP70的表达,并用MIAS－2000图文分析系统分析大鼠海马HSP70阳性细胞百分率、阳性细胞密度和灰度值。结果 单独应用氯胺酮可在大鼠海马表达HSP70;预先给予氟哌啶醇能抑制氯胺酮诱导的HSP70表达,且随着剂量的增加,其抑制作用增强;在使用氯胺酮后给予氟哌啶醇,不能减少HSP70的表达。结论 氯胺酮可诱导HSP70在海马的表达,提示海马的神经元可能受到损害;氟哌啶醇可以预防氯胺酮所致的神经元损害,但对已造成的神经元损害无治疗作用。     

Effect on airway resistance of ketamine by aerosol in guinea pigs

The effect of aerosolized ketamine hydrochloride was investigated by measuring airway resistance with a two-compartment plethysmograph in guinea pigs challenged with histamine. In the first phase of the study, treatment with ketamine prior to histamine challenge did not protect against elevation of airway resistance. In the second phase of the study, ketamine inhalation after histamine challenge did not significantly diminish airway resistance. Aerosolized ketamine is not recommended for use in human subjects with asthma.     

Does ketamine affect intraoperative electrophysiological monitoring in children undergoing selective posterior rhizotomy?

Objective: Direct dorsal rootlet stimulation with intraoperative electrophysiological monitoring is an adjunct to clinical evaluation during selective posterior rhizotomy. The purpose of this study was to evaluate the impact of ketamine on intraoperative electrophysiological monitoring during selective posterior rhizotomy. Specifically, we sought to determine if low dose ketamine given as part of the anesthesia was associated with changes in intraoperative electrophysiological monitoring in patients who underwent selective posterior rhizotomy. Methods: A retrospective cohort study was conducted using anesthetic records and electrophysiological records of 32 children who had intraoperative electrophysiological monitoring during selective posterior rhizotomy under general anesthesia. Administration and dosage of ketamine preceding the stimulation of dorsal roots was determined from the anesthetic record. A pediatric neurologist, blinded to patient, and to ketamine exposure, evaluated different electrophysiological criteria. Results: Eight children received ketamine and 24 did not receive it. The mean average dose of ketamine was 0.18 mg·kg^?1 (sd : 0.04). We did not find any statistically significant difference in intraoperative electrophysiological response between the ketamine and the control groups. However, we noted some trends: Administration of ketamine preceding the stimulation of dorsal roots was associated with a lower maximal threshold (2.7 mA vs 3.5 mA, P = 0.663) and root thresholds compared with children who did not receive ketamine. In addition, the train response following delivery of the suprastimulation tended to last longer with the presence of ketamine. Conclusions: Administration of low dose ketamine preceding the stimulation of dorsal roots during selective posterior rhizotomy might be associated with lower maximal thresholds and a more sustained train response following stimulation. Physicians should be aware of this finding in order to avoid misinterpreting intraoperative electrophysiological monitoring.     

Ventilatory response to CO2 following intravenous ketamine in children

The effects of intravenous ketamine (bolus of 2 mg.kg-1 followed by a continuous infusion at a rate of 40 micrograms.kg-1.min-1) on ventilatory response to carbon dioxide were studied in nine children ranging in age from 6 to 10 yr and in weight from 20 to 48 kg. Ketamine did not affect resting respiratory rate, tidal volume, end-tidal CO2 tension (PETCO2), or minute ventilation. Five minutes after the ketamine bolus, the slope VE/PETCO2 decreased significantly (P less than 0.05) from 1.71 +/- 0.47 to 1.05 +/- 0.23 1.min-1.mmHg-1 (mean +/- SD). After 30 min of continuous iv ketamine infusion, the slope returned to 1.65 +/- 0.44 1.min-1.mmHg-1, a significantly higher value (P less than 0.05) compared with the nadir and not significantly different from control. The minute ventilation at a PETCO2 of 60 mmHg decreased from 824 +/- 98 to 626 +/- 26 ml.kg-1.min-1 5 min after iv ketamine, and remained depressed (640 +/- 125 ml.kg-1.min-1 P less than 0.05) throughout the 30-min ketamine infusion. In addition, the slope VT/PETCO2 and the VT 60 did not change during the study; nonetheless, the slope f/PETCO2 and the f 60 decreased significantly following iv bolus ketamine, and the f 60 remained significantly decreased following ketamine infusion. The authors conclude that clinically useful doses of iv ketamine significantly alter ventilatory control in children.     

Epidural ketamine for postoperative pain relief after gynecologic operations: a double-blind study and comparison with epidural morphine

This double-blind study evaluates whether ketamine given epidurally is effective for postoperative pain relief, and compares the effects of epidural ketamine with those of epidural morphine. Sixty-eight patients undergoing abdominal gynecologic surgery were randomly assigned into six groups (control; ketamine 4, 6, and 8 mg in saline; 6 mg in 10% glucose; morphine 3 mg). All patients were anesthetized with thiopental, nitrous oxide, and enflurane, and drugs were administered epidurally at the end of the operation. The duration of analgesia in the ketamine groups did not differ from that in control patients and the difference in diluent had no observable effects. Significantly, none of the patients in the morphine group needed additional analgesics within 24 hr, whereas 85% in the other five groups did. We conclude that ketamine administered epidurally is inadequate for postoperative pain relief after gynecologic operations.     

The effects of ketamine on venous capacitance in rats

The purpose of this study was to examine the effects of ketamine and pentobarbital on venous capacitance in rats. Venous capacitance was assessed by measuring the mean circulatory filling pressure (MCFP) at three levels of blood volume in conscious rats as well as during anesthesia with ketamine (125 mg/kg, ip) or pentobarbital (50 mg/kg, ip). MCFP was measured during brief periods of circulatory arrest produced by inflating an indwelling balloon in the right atrium. MCFP was maintained during ketamine anesthesia at a level similar to that measured in conscious animals, while it was decreased (P less than 0.01) during pentobarbital anesthesia both at normal blood volume and following hemorrhage. These results suggest that ketamine did not alter but pentobarbital increased venous capacitance. The slope of the regression line relating MCFP and blood volume was not altered by ketamine but was increased (P less than 0.05) by pentobarbital, which suggests that ketamine did not alter but pentobarbital decreased total vascular compliance. These results suggest that ketamine maintains but pentobarbital decreases venous tone.     

Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia

N-methyl-D-aspartate (NMDA) receptor antagonists enhance opioid-induced analgesia. The plasma concentration of ketamine, an NMDA receptor antagonist that enhances epidural morphine-and-bupivacaine-induced analgesia, is not known. We examined 24 patients with lung carcinoma or metastatic lung tumor who underwent video-assisted thoracic surgery in a placebo-controlled, double-blind manner 4 h after emergence from anesthesia. The morphine + ketamine group (n = 8) and morphine + placebo group (n = 8) received 5 mL volume of 2.5 mg morphine and 0.25% bupivacaine and the placebo + ketamine group (n = 8) received 5 mL volume of saline and 0.25% bupivacaine epidurally at the end of skin closure. Four hours after this anesthesia, in the morphine + ketamine and placebo + ketamine groups, ketamine was administered to successively maintain a stable plasma ketamine concentration of 0, 10, 20, 30, 40, and 50 ng/mL by a target-controlled infusion device, and patients assessed the levels of pain at rest, pain on coughing, somnolence (drowsiness), and nausea using a 100-mm visual analog scale (VAS). In the morphine + placebo group, a placebo (saline) was similarly administered instead of ketamine. In the morphine + ketamine group, the VAS scores for pain at rest and pain on coughing significantly decreased on ketamine administration at a plasma concentration of 20 ng/mL or larger compared with the respective baseline VAS scores (P < 0.05 each). In the placebo + ketamine group, the VAS scores for pain at rest and pain on coughing did not significantly change at any plasma concentration of ketamine as compared to the morphine + placebo group. In the morphine + ketamine group, a plasma concentration of ketamine larger than 20 ng/mL did not further reduce VAS scores for pain at rest and pain on coughing. The VAS scores for drowsiness were comparable among the three groups at any plasma concentration of ketamine. Ketamine at a plasma concentration of 20 ng/mL or larger may enhance epidural morphine-and-bupivacaine-induced analgesia. As an adjunct with epidural morphine-and-bupivacaine and considering the safety of small doses, the minimal plasma concentration of ketamine given IV may be approximately 20 ng/mL.     

Ketamine stereoselectively affects vasorelaxation mediated by ATP-sensitive K(+) channels in the rat aorta

BACKGROUND: The effect of ketamine on vasodilation mediated by adenosine triphosphate (ATP)-sensitive K(+) channels has not been studied. The present study was designed to determine whether ketamine might stereoselectively affect vasorelaxation induced by an ATP-sensitive K(+) channel opener in the isolated rat aorta. METHODS: Rings of the rat aorta with or without endothelium were suspended for isometric force recording. During contraction to phenylephrine (3 x 10(-7) M), vasorelaxation in response to an ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 10(-5) M) or a nitric oxide donor sodium nitroprusside (10(-10) to 10(-5) M) was obtained. Glibenclamide (10(-5) M), S(+) ketamine (10(-4) M), or ketamine racemate (10(-5) to 10(-4) M) was applied 15 min before addition of phenylephrine. RESULTS: Vasorelaxation induced by levcromakalim was completely abolished by an ATP-sensitive K(+) channel antagonist glibenclamide (10(-5) M) in the aorta with or without endothelium. Ketamine racemate (3 x 10(-5) to 10(-4) M) significantly inhibited this vasorelaxation in a concentration-dependent fashion, whereas S(+) ketamine did not affect the relaxation. However, the highest concentration of ketamine racemate and S(+) ketamine used in the present study did not alter vasorelaxation in response to sodium nitroprusside in the aorta without endothelium. CONCLUSION: In the isolated rat aorta, clinically relevant concentrations of ketamine racemate can inhibit relaxation induced by an ATP-sensitive K(+) channel opener, whereas S(+) ketamine did not produce any inhibitory effect on this vasorelaxation. These results suggest that ketamine stereoselectively alters vasodilation ATP-sensitive K(+) channels in the conduit artery.     

Ketamine does not trigger malignant hyperthermia in susceptible swine

The use of ketamine in individuals susceptible to malignant hyperthermia (MH) is controversial. We describe our experience with ketamine used for induction and/or maintenance of anesthesia in our herd of swine inbred for susceptibility to MH. A total of 76 MH-susceptible swine were given a total of 112 general anesthetics using ketamine as the induction drug. In 34 of these anesthetics, anesthesia was also maintained with ketamine. Signs of MH did not develop in response to ketamine in any of the pigs.     

The effects of nitrous oxide and ketamine on the bispectral index and 95% spectral edge frequency during propofol-fentanyl anaesthesia

In this study, we have sought to establish whether N2O and ketamine alter the bispectral index during propofol-fentanyl anaesthesia. Fourteen surgical patients were randomly assigned to one of two groups: the N2O group (n = 7) and the ketamine group (n = 7). In both groups, anaesthesia was induced with propofol 1.5-2 mg kg-1 and fentanyl 2 micrograms kg-1 and maintained with propofol 5-7 mg kg-1 hr-1 to target the bispectral index between 40 and 50. After the bispectral index value had stabilized the propofol infusion rate was fixed. In the N2O group, the following concentrations of N2O were subsequently inhaled at 20-min intervals; 20, 40, 60 and 70%, and then N2O was terminated. In the ketamine group, ketamine (0.4 mg kg-1 + 1.0 mg kg-1h-1) was given. The bispectral index and 95% spectral edge frequency were recorded 20 min after each change in concentration of N2O or ketamine infusion. The bispectral index and 95% spectral edge frequency did not change significantly in the N2O group, but increased significantly from 44.1 +/- 0.7 and 16.0 +/- 0.5 to 58.6 +/- 1.4 and 19.5 +/- 0.3 (P < 0.01), respectively, in the ketamine group. Additional N2O or ketamine did not decrease the bispectral index and 95% spectral edge frequency values. The depth of sedation should be assessed carefully using a bispectral index monitor when these anaesthetic agents are used together.     

Intramuscular low-dose ketamine versus pethidine for postoperative pain treatment after thoracic surgery

In a double-blind prospective study the effects of low-dose intramuscular ketamine (1 mg/kg) were compared to pethidine (1 mg/kg) in the treatment of pain after pulmonary surgery. Thirty patients were admitted to the study and postoperatively randomized to either a ketamine or a pethidine group. The analgesic effect was evaluated using a scale ranging from 0 to 10, where 0 denoted no pain and 10 severe pain. We did not find any significant difference between the analgesic effect of ketamine and pethidine; however, the duration of action of ketamine appeared to be slightly longer. Throughout the study PaCO2 was significantly lower in the ketamine group. PaO2 increased through the study in both groups and was significantly higher after 2 h. Heart rates increased significantly only in the pethidine group. Mean arterial pressures remained unchanged and the respiratory frequencies were similar in the two groups. The incidence of adverse reactions was low and not significantly different between the groups. The findings indicate that low-dose intramuscular ketamine is a potent analgesic for postoperative analgesia following thoracic surgery and that it has no respiratory depressive effect.