The combined effects of sevoflurane and remifentanil on central respiratory activity and nociceptive cardiovascular responses in anesthetized rabbits.

We studied the effects of sevoflurane and remifentanil, alone and in combination, on phrenic nerve activity (PNA), resting heart rate (HR), arterial pressure (MAP), and changes in HR (delta HR) and MAP (delta MAP) evoked by electrical stimulation of tibial nerves in anesthetized rabbits. The 50% effective dose (95% confidence intervals) for the depressant effects of sevoflurane on delta HR, delta MAP, and PNA were 2.3 (1.8%-2.6%), 2.7 (2.3%-2.9%), and 3.4 (3.1%-3.7%), respectively, and for remifentanil were 0.100 (0.050-0.132), 0.850 (0.720-1.450), and 0.090 (0.080-0.145) microgram.kg-1.min-1, which were reduced to 0.046 (0.021-0.065), 0.110 (0.080-0.200), and 0.030 (0.020-0.040) microgram.kg-1.min-1, respectively, by 1% sevoflurane. Depression of evoked cardiovascular responses relative to PNA was greater for sevoflurane and less for remifentanil both alone and in combination with sevoflurane. Sevoflurane acted synergistically with remifentanil on PNA and delta MAP, but not delta HR, for which their combined effect was additive. Coadministration of 1% sevoflurane with the highest infusion rate of remifentanil (1.6 micrograms.kg-1.min-1) used during combined administration reduced resting HR and MAP by 25% (P < 0.05) and 41% (P < 0.05), respectively, which was greater than the predicted reductions of only 14% and 15% if their combined effects had been additive. We conclude that sevoflurane caused a relatively greater depression of nociceptive cardioaccelerator and pressor responses compared with PNA and vice versa for remifentanil. When coadministered, their combined effects on PNA, resting HR, MAP, and delta MAP were synergistic, whereas they were merely additive for delta HR. Implications: Although sevoflurane caused relatively greater depression of nociceptive cardiovascular responses compared with phrenic nerve activity, remifentanil either alone or combined with sevoflurane caused a much greater depression of phrenic nerve activity than cardio-accelerator and pressor responses. This could imply that, during major surgery using anesthesia combining sevoflurane and remifentanil, spontaneous ventilation is not acceptable, and depression of the resting circulation may be much greater than anticipated.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

瑞芬太尼在气管拔管中对心血管反应的影响

目的观察术后应用瑞芬太尼对气管拔管时心血管反应的影响。方法40例腹腔镜下胆囊切除术的患者，均采用快诱导气管插管静吸复合全麻。术中维持：异氟醚吸人，瑞芬太尼泵注。术毕将患者随机分为两组，瑞芬太尼组术毕将瑞芬太尼剂量减少一半，静滴至拔管后即刻；对照组术毕即停止静滴瑞芬太尼。结果对照组在吸引及拔管后3min，HR明显加快（P〈0．05）。在拔管时及拔管后SBP升高明显。结论延长瑞芬太尼静滴时间可以减轻气管拔管时的心血管不良反应。     

Antibacterial activity of remifentanil and mixtures of remifentanil and propofol

STUDY OBJECTIVE: To investigate the antibacterial activity of glycine, which is contained in remifentanil, when combined with propofol. DESIGN: Prospective study. SETTING: Departments of anesthesiology and microbiology of a university hospital. MEASUREMENTS: Growth of the microorganisms Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans in propofol 1%; saline dilutions of remifentanil at one-, 10-, and 100-microg/mL concentrations; and 1:1 mixtures of propofol with remifentanil solutions was determined. MAIN RESULTS: Remifentanil inhibits bacterial growth in a concentration-dependent manner. The antibacterial effects were more pronounced with Staphylococcus aureus and Pseudomonas aeruginosa at cultures obtained at the fifth hour. The inhibition of bacterial growth was less influenced with Escherichia coli and Candida albicans. CONCLUSIONS: Propofol and remifentanil mixtures decreased bacterial growth, and combinations may reduce the infectious complications from accidentally contaminated propofol.     

Propofol depresses the activity of hypoglossal nerve more than that of phrenic nerve in rabbits

BACKGROUND: Respiratory depression, such as obstruction of upper airway and inadequate ventilation, often appears during sedation and anesthesia. We studied the effect of propofol on the upper airway patency and the inspiratory drives. METHODS: Experiments were performed on the adult rabbits vagotomized, paralyzed and ventilated with nitrous oxide-oxygen-sevoflurane. We evaluated and compared depressant effect of propofol on the peak amplitude of both hypoglossal nerve (AMP-HG) and phrenic nerve (AMP-PH) activities, inspiratory time (Ti), expiratory time (Te) and respiratory cycle (Tc). RESULTS: Bolus injections of propofol transiently reduced AMP-HG more than AMP-PH (18 and 70% of control, respectively). But AMPs returned to the control levels about 10-15 min after the injection. For 0.5 mg.kg-1.min-1 continuous infusion, propofol soon began to reduce both AMPs. AMP-HG was reduced to about 20% and AMP-PH to 60% of control. Administration of propofol with 1.0 mg.kg-1.min-1 caused more reduction in AMPs with respiratory slowing and AMP-HG disappeared in some animals. CONCLUSION: During the sedation with low dose of propofol, we need to pay attention to potential upper airway obstruction. In addition to the above, high doses of propofol could reduce spontaneous inspiratory drive, and we need to keep both upper airway patency and sufficient ventilation.     

Comparison of clonidine with fentanyl on phrenic nerve activity and their interaction in anaesthetized rabbits

We have compared the effects of clonidine and fentanyl on phrenicnerve activity in anaesthetized rabbits during artificial ventilation.Both drugs caused dose-dependent inhibition of phrenic nerveactivity and complete abolition in all experiments. The calculatedED₅₀ values were 3.7µg kg^–1 for clonidine and 3.9µgkg^–1 for fentanyl. Pretreatment with clonidine 1 µgkg^–1i.v. depressed phrenic nerve activity to 81.8% ofcontrol values. This effect was additive with subsequent dosesof fentanyl which was confirmed with an ED₅₀, isobologram. Weconclude that clonidine has the potential for deleterious respiratoryeffects at doses similar to those of fentanyl, but the interactionbetween the two drugs is additive and hence differs from theirknown synergistic antinociceptive interaction.     

不同剂量丙泊酚对老年患者心血管功能的影响

目的　监测丙泊酚用于老年患者全麻诱导期间对心脏功能的影响。方法　ASAⅠ～Ⅱ级拟行腹部手术的老年患者 30例 ,随机分成三组 ,经鼻放置食管超声多普勒探头。分别静注丙泊酚 1 0mg/kg(Ⅰ组 )、1 5mg/kg(Ⅱ组 )和 2 0mg/kg(Ⅲ组 )。观察MAP、HR、心输出量 (CO)、每搏量 (SV)、全身血管阻力 (TSVR)、血流加速度 (Acc)、峰流速 (PV)、左心室射血时间指数 (LVETI)值。结果　Ⅲ组在注药后 5、10min时HR、CO、SV、TSVR、Acc、PV、LVETI值与麻醉前比差异均有极显著性 (P <0 0 1)。结论　 2 0mg/kg丙泊酚诱导抑制老年人心肌收缩功能。丙泊酚用于老年患者全麻诱导时的剂量宜为 1 0～ 1 5mg/kg。     

异丙酚麻醉下瑞芬太尼抑制病人气管插管和切皮时心血管反应的效应室靶浓度

目的测定异丙酚麻醉期间瑞芬太尼抑制病人气管插管和切皮时心血管反应的效应室靶浓度(EC50和EC95)。方法择期全麻手术病人60例,ASAⅠ或Ⅱ级,年龄加～65岁,体重40～75 kg,随机分为6组(n=10):瑞芬太尼靶控输注(TCI),血浆靶浓度分别为1、2、3、4、5、6 ng/ml;异丙酚TCI,效应室靶浓度均为4.0μg/mI。病人意识消失后静脉注射维库溴铵0.15 mg/kg,气管插管。插管后2 min暂停瑞芬太尼TCI,切皮前10 min再以诱导时相同浓度瑞芬太尼TCI。记录入室安静时(基础值)、诱导后最低、插管后2 min内最高、切皮前1 min、切皮后2 min内最高的平均动脉压(MAP)和心率(HR)。MAP和HR诱导后最低值与插管后2 min内最高值、切皮前1 min与切皮后2 min内最高值比较升高>15%为心血管阳性反应。采用Probit法计算瑞芬太尼EC50和EC95。结果瑞芬太尼抑制气管插管时心血管反应的EC50为4.41 ng/ml,95%可信区间(95%CI)为3.97～5.05 ng/ml;相应的EC95为6.42 ng/ml,95%CI为5.54～8.09 ng/ml。瑞芬太尼抑制切皮时心血管反应的EC50为2.05 ng/ml,95%CI为1.36～2.59 ng/ml;相应的EC95为3.89 ng/ml,95%CI为3.20～5.71 ng/ml。结论异丙酚效应室靶浓度为4.0μg/ml时,靶控输注瑞芬太尼抑制病人对气管插管和切皮诱发的心血管反应呈剂量依赖性,其效应室EC50分别为4.41 ng/ml和2.05 ng/ml。     

Studies on the phrenic nerve and diaphragmatic plexus in rabbits and gerbils

Studies on nerve fibres within the phrenic nerve and in the diaphragmatic plexus were carried out in one species, the gerbil, a small desert rodent. The resistance of this small mammal to surgical insult enabled experimental intrathoracic transection of the phrenic nerve to be carried out so that the results in 10 animals could be observed within the diaphragmatic plexus, the phrenic nerve, and the phrenic nucleus. The findings in the diaphragmatic plexus and in the nerve trunk strongly resemble corresponding results for other animals with regard to `persisting' fibres. The phrenic nucleus, however, is much more extensive in this mammal than has been found in any other species; it is represented within the second to sixth cervical segment, its rostral extremity occupying the intermediolateral part of the spinal grey matter. The possible functional significance of these findings is discussed in the light of the mixed functions of the diaphragm, either voluntary or involuntary.     

雷米芬太尼和丙泊酚对老年大鼠认知功能的影响

目的 探讨雷米芬太尼和丙泊酚对老年大鼠认知功能及其海马β淀粉样蛋白(Aβ42)和半胱天冬酶-3(Caspase-3)表达的影响.方法 雄性18月龄SD大鼠50只,随机均分成五组:对照1周组(N1组)、雷米芬太尼1周组(R1组)、丙泊酚1周组(P1组),对照3周组(N3组)、丙泊酚3周组(P3组).R1组尾静注雷米芬太尼60μg/kg,随后静脉泵注15 μg·kg-1·min-1,维持1h.P1、P3组腹腔注射60 mg/kg丙泊酚,待出现翻正反射时追加1/2首剂量,共追加2次.N1、N3组腹腔注射等量生理盐水.N1、P1、R1组处理后第1周行Morris水迷宫实验.N3、P3组处理后第3周行水迷宫实验,每天4次,连续4 d.测试结束后灌注固定取肭.行海马组织切片的HE染色和免疫组化染色,观察海马结构及测定海马Aβ42和Caspase-3表达.结果 (1)水迷宫结果 :潜伏期测试各组间同一时点与对照组比较,仅在第1周的第2天和第3天,P1组较N1组差异有统计学意义(P<0.05或P<0.01);探索试验中通过原平台次数各组与对照组比较在第1周和第3周均无统计学意义.(2)海马HE染色:光镜下各组大鼠海马结构未见明显片常.(3)海马免疫组化染色:海码CA1区Aβ42和Caspase-3阳性件表达细胞数各组与对照组比较均无统计学意义.结论 麻醉剂量的丙泊酚可致老年大鼠短期认知功能障碍,雷米芬太尼无此作用.丙泊酚和雷米芬太尼麻醉后4 d或3周对大鼠海马Aβ42和Caspase-3的表达均尤影响.     

吸入麻醉药对兔肾交感神经活动的影响

目的比较吸入麻醉药对交感神经活动和血液动力学的影响。方法18只兔被随机分为三组:安氟醚组、异氟醚组和地氟醚组。兔麻醉、肌松和人工通气后,暴露肾交感神经并记录其电生理活动。分别吸入呼气末浓度为0.8%、1.6%、2.4%、3.2%安氟醚,0.6%、1.2%、1.8%、2.4%异氟醚,或3.0%、6.0%、9.0%、12.0%地氟醚。结果交感神经活动在兔吸入2.4%安氟醚、0.6%异氟醚和6.0%地氟醚时分别增加到44%、36%和32%,当进一步增加吸入麻醉药的浓度则抑制肾交感神经活动。血压随着吸入麻醉药浓度的增加不断下降而心率除了2.4%异氟醚诱发心率减慢外无明显变化。结论安氟醚、异氟醚和地氟醚具有双向作用,低浓度兴奋交感神经,高浓度抑制交感神经活动和降低血压。     

Effects of intravenously administered lidocaine on pulmonary vagal afferents and phrenic nerve activity in cats

The ability of lidocaine to suppress activity of single vagal afferent fiber and that of phrenic nerve was studied in 20 cats anesthetized with pentobarbital. Slowly adapting stretch receptors (SAR, n = 16) and rapidly adapting stretch receptors (RAR, n = 7) were identified by their discharge pattern to pulmonary inflation. Intravenous lidocaine (1mg·kg^–1 or 2mg·kg^–1) produced a suppression of SAR activity but not of RAR activity. Suppression of phrenic nerve activity lasted much longer than that of SAR. These findings indicate that iv lidocaine acts more dominantly on CNS than on peripherals. We conclude that iv lidocaine prevents cough and hemodynamic changes caused by airway manipulation mainly through its action on CNS and not on peripherals (peripheral nerves or their receptor).(Aoki M, Harada Y, Namiki A, et al.: Effects of intravenously administered lidocaine of pulmonary vagal afferents and phrenic nerve activity in cats. J Anesth 6: 395–400, 1992)     

瑞芬太尼对心血管系统的影响及其机制研究现状

瑞芬太尼作为一种新型超短效的阿片类镇痛药已经被广泛应用于临床,其可能造成的心率减慢、血压降低等心血管系统抑制作用也备受关注.现就瑞芬太尼对不同年龄患者心血管系统的影响及相关机制的研究进展进行分析探讨.     

The effect-site concentration of remifentanil blunting cardiovascular responses to tracheal intubation and skin incision during bispectral index-guided propofol anesthesia

We sought to determine the effect-site concentration of remifentanil blunting sympathetic responses to tracheal intubation and skin incision during bispectral index (BIS)-guided propofol anesthesia. Forty-one ASA physical status I-II patients, aged 20-65 yr and undergoing major abdominal surgery, were randomly assigned to one of two groups: tracheal intubation (group TI, n = 20) or skin incision (group SI, n = 21). All patients received a target-controlled infusion of propofol of 4 microg/mL, which was then adjusted to maintain a BIS value ranging between 40 and 50. The effect-site concentration of remifentanil blocking the sympathetic responses to tracheal intubation and skin incision in 50% of cases (Ce50) was determined using an up-and-down sequential allocation method. The mean (95% confidence interval [CI]) Ce50 of remifentanil was 5.0 ng/mL for TI (95% CI, 4.7-5.4 ng/mL) and 2.1 ng/mL for SI (95% CI, 1.4-2.8 ng/mL). This study shows that effect-site concentrations of remifentanil of 5 ng/mL and 2 ng/mL are effective in blunting sympathetic responses to tracheal intubation and skin incision in 50% of patients when combined with a BIS-guided target controlled infusion of propofol.     

瑞芬太尼对兔内毒素性急性肺损伤的影响

目的 探讨瑞芬太尼对兔内毒素性急性肺损伤(Au)的影响.方法 健康成年雄性新西兰大白兔30只,体重2.5～3.5 kg,随机分为5组(n=6):对照组(C组)、ALI组、低剂量瑞芬太尼组(LR组)、中剂量瑞芬太尼组(MR组)和高剂量瑞芬太尼组(HR组).C组经30 min静脉输注生理盐水10 ml;ALI组经30 min静脉输注大肠杆菌内毒索(LPS)0.5 mG/kg;LR组、MR组和HR组分别静脉输注瑞芬太尼0.2、0.4和0.8μg·kg~(-1)·min~(-1)至处死,输注15 min时开始给予LPS,方法同ALI组.于LPS输注前即刻(T_0)、输注结束后1、2.5、5.5 h时记录平均动脉血压(MAP)、心率(HR)和气道峰压(P_(peak),测定动脉血氧分压(PaO_2)和血浆细胞间粘附分子1(ICAM-1)浓度,称量肺组织湿重(W)和干重(D),计算W/D比,并在光镜和电镜下观察肺组织病理学结果.结果 与C组比较,ALI组MAP、HR和PaO_2,降低,W/D比、P_(peak)和血浆ICAM-1浓度升高(P<0.05);与ALI组比较,LR组、MR组和HR组MAP、HR 升高,肺组织W/D比降低,P(peak)和血浆ICAM-1浓度降低,PaO_2升高(P<0.05);与LR组比较,MR组和HR组MAP、HR、P(peak)、血浆ICAM-1浓度和肺组织W/D比降低,PaO_2升高(P<0.05);与MR组比较,HR组注肺组织W/D比降低,PaO_2升高(P<0.05).LR组、MR组和HR组肺组织病理学损伤较ALI组减轻.结论 瑞芬太尼可减轻兔内毒素性急性肺损伤,且呈剂量依赖性,其机制可能与抑制ICAM-1的表达有关.     

瑞芬太尼预先给药对兔心肌缺血再灌注损伤的影响

目的 评价瑞芬太尼预先给药对兔心肌缺血再灌注损伤的影响.方法 健康家兔30只,月龄12～18个月,体重2.5～3.5kg,随机分为3组(n=10):缺血再灌注组(IR组)、低剂量瑞芬太尼预先给药组(R1组)和高剂量瑞芬太尼预先给药组(R2组).3组均采用结扎左冠状动脉前降支30 min开放的方法制备心肌缺血再灌注模型,R1组和R2组分别静脉输注瑞芬太尼1.65、3.30μg·kg-1·min-130 min时进行缺血,IR组给予等容量生理盐水.于给药前(基础状态)、给药结束时、缺血30 min、再灌注6 h时采集静脉血样,测定血清心肌肌钙蛋白I(cTnI)和MB型肌酸激酶同工酶(CK-MB)的浓度.再灌注结束时处死动物,取心肌组织,光镜和电镜下观察病理学结果.结果 与IR组比较,R1组和R2组血清cTnI和CK-MB浓度降低(P＜0.01);与R1组比较,R2组血清cTnI浓度降低(P＜0.01).R1组和R2组心肌病理学损伤程度均轻于IR组,且R2组心肌病理学损伤程度轻于R1组.结论 瑞芬太尼预先给药可减轻兔心肌缺血再灌注损伤,且与剂量有关.     

异丙酚麻醉诱导期间不同剂量瑞芬太尼对病人气管插管心血管反应的影响

目的比较异丙酚麻醉诱导期间不同剂量瑞芬太尼对病人气管插管心血管反应的影响，寻找瑞芬太尼复合异丙酚气管插管的合适剂量。方法择期行腹腔镜胆囊切除术病人36例，ASAⅠ或Ⅱ级，年龄20～65岁，随机分为3组（n=12）：瑞芬太尼1、1．5、2μg／kg分别为复合异丙酚1．5μg／kg组（Ⅰ、Ⅱ、Ⅲ组）。依次静脉注射咪唑安定0．03mg／kg、异丙酚1．5mg/kg、维库溴铵0．1mg／kg以及瑞芬太尼麻醉诱导，2min后气管插管，进行机械通气，呼吸频率12次／min，潮气量8～10ml／kg，维持呼气末二氧化碳分压35～45mmHg。持续监测血压（平均动脉压、舒张压、收缩压）、心率（HR）以及听觉诱发电位指数（AAI），并记录病人有无气管插管时呛咳和肌肉强直、术中知晓等反应。结果与基础值比较，三组气管插管前即刻血压及Ⅲ组气管插管后即刻舒张压均降低，Ⅲ组气管插管后即刻血压低于Ⅰ组（P〈0．05）；HR组间及组内比较差异无统计学意义；三组间AAI差异无统计学意义。结论异丙酚1．5mg／kg麻醉诱导期间瑞芬太尼1或1．5μg／kg是病人气管插管时的合适剂量。     

Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly

Background. We compared the effects of remifentanil and alfentanilon arterial pressure and heart rate at induction of anaesthesiaand tracheal intubation in 40 ASA I–III patients agedgreater than 65 yr, in a randomized double-blind study. Methods. Patients received either remifentanil 0.5 µgkg^–1 over 30 s, followed by an infusion of 0.1 µgkg min^–1 (group R) or alfentanil 10 µg kg^–1over 30 s, followed by an infusion of saline (group A). Anaesthesiawas then induced with propofol, rocuronium, and 1% isofluranewith 66% nitrous oxide in oxygen. Results. Systolic arterial pressure (SAP) and mean arterialpressure (MAP) decreased after the induction of anaesthesia(P<0.05) and increased for 3 min after intubation in bothgroups (P<0.05), but remained below baseline values throughout.Heart rate remained stable after induction of anaesthesia butincreased significantly from baseline after intubation for 1and 4 min in groups R and A, respectively (P<0.05). Therewere no significant between-group differences in SAP, MAP, andheart rate. Diastolic pressure was significantly higher in groupA than group R at 4 and 5 min after intubation (P<0.05).Hypotension (SAP <100 mm Hg) occurred in four patients ingroup R and three patients in group A. Conclusions. Remifentanil and alfentanil similarly attenuatethe pressor response to laryngoscopy and intubation, but theincidence of hypotension confirms that both drugs should beused with caution in elderly patients. Br J Anaesth 2002; 88: 430–3