Remifentanil reduces auditory and somatosensory evoked responses during isoflurane anaesthesia in a dose-dependent manner

We studied 60 patients during stable isoflurane anaesthesia (0.4 MAC) after premedication with temazepam. Patients were allocated randomly to one of three dose regimens of remifentanil: 1 microgram kg-1 i.v. over 1 min and an infusion of 0.2 microgram kg-1 min-1 (low dose); 2.5 micrograms kg-1 and 0.5 microgram kg-1 min-1 (medium dose); and 5 micrograms kg-1 and 1 microgram kg-1 min-1 (high dose). The auditory (AER) and median nerve somatosensory (SER) responses were elicited throughout, and recorded before and after tracheal intubation, and surgical incision, together with systolic and diastolic arterial pressure and heart rate. Venous blood concentrations of remifentanil were measured at the above times. After administration of remifentanil, Pa and Nb amplitudes of the AER increased at the low dose, remained constant at the medium dose and decreased at the high dose. This dose- related effect was linear and significant (P = 0.012, P = 0.05). Pa amplitude correlated inversely with remifentanil blood concentrations before and after intubation and incision (P = 0.002, P < 0.001, P < 0.001 and P < 0.001). In the SER, P15-N20 amplitudes decreased after administration of remifentanil (P < 0.001), whereas P25-N35 and N35-P45 amplitudes increased at all dose concentrations (P < 0.001 and P < 0.001). After intubation, P15-N20 and N35-P45 amplitudes increased at the low dose, did not change at the medium dose and decreased at the high dose (P = 0.001, P = 0.027). After remifentanil, systolic and diastolic arterial pressure and heart rate decreased in a linearly dose- related manner (P = 0.033, P < 0.001, P < 0.001). At all doses the three variables increased after intubation (P = 0.001, P < 0.001, P < 0.01), and systolic and diastolic arterial pressure increased after incision (P = 0.027, P = 0.039).      

Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with anaesthetic-sparing effects. We have determined the pharmacodynamic and pharmacokinetic interactions between dexmedetomidine and isoflurane in volunteers. Nine male subjects were allocated randomly to receive isoflurane anaesthesia preceded by infusion of dexmedetomidine on three separate occasions, 2 weeks apart. Dexmedetomidine target plasma concentrations were 0.0 (placebo), 0.3 ng ml-1 (low-dex) and 0.6 ng ml- 1 (high-dex). End-tidal isoflurane concentrations at which gross purposeful movement and response to verbal commands occurred were identified. In the recovery period, sedation scores and digit symbol substitution tests were recorded. Venous blood samples were obtained before, during and after anaesthesia at predetermined intervals for measurement of plasma concentrations of dexmedetomidine and calculation of standard pharmacokinetic indices (AUC, Cl, Vss, T1/2 alpha, T1/2 beta). The end-tidal isoflurane concentration at which 50% of subjects first responded to the tetanic stimulus was 1.05% in the placebo group, 0.72% in the low-dex group and 0.52% in the high-dex group. We conclude that dexmedetomidine decreased isoflurane requirements in a dose- dependent manner and reduced heart rate, systolic and diastolic arterial pressures. Sedation and slight impairment of cognitive function persisted for several hours after anaesthesia and the end of infusion of dexmedetomidine. Isoflurane did not appear to influence the pharmacokinetics of dexmedetomidine.      

SOMATOSENSORY AND AUDITORY EVOKED RESPONSES RECORDED SIMULTANEOUSLY: DIFFERENTIAL EFFECTS OF NITROUS OXIDE AND TSOFLURANE

Auditory (AER) and somatosensory evoked responses (SSER) wererecorded simultaneously in eight patients under anaesthesiabefore surgery. We studied the effects of equi-MAC end-expiratoryconcentrations of isoflurane (0.65–0.75%) and nitrousoxide (60–65%). The anaesthetics were changed at randomin three consecutive 10-min periods so that each patient receivedboth drugs. From the AER recorded from the vertex and inion.Pa and Nb latency and amplitude were measured. N13, P20 latencyand N13 amplitude were measured from SSER recordings from theneck and P15, N20. P25, N35, P45 latency and P15-N20, N20-P25,P25-N35 and N35-P45 amplitude from the scalp over the hand areaof the sensory cortex. Compared with nitrous oxide, isofluranesignificantly increased the latencies of the AER waves Pa (P= 0.02) andNb (P = 0.02), and the SSER waves N20 (P = 0.001)and P25 (P = 0.04). We were unable to demonstrate significantdifferences in Pa and Nb amplitude between isoflurane and nitrousoxide that we had seen previusly. However, the amplitude ofthe SSER wave N20 was reduced significantly by nitrous oxidecompared with isoflurane (P = 0.0004). This wave (N20) is thoughtto emanate from the thalamo-cortical radiations, and our findingsmay be explained by an analgesic effect of nitrous oxide mediatedby endogenous opioids. ^*Present address: Department of Anaesthesia, Royal Free Hospital,Pond Street, London NW3.     

Cardiopulmonary bypass-induced changes in plasma concentrations of propofol and in auditory evoked potentials

Unbound, rather than total, plasma concentrations may be related to the anaesthetic action of propofol. Therefore, we measured plasma concentrations of propofol and recorded Nb wave latencies of auditory evoked potentials (AEP) during continuous infusion of propofol in 15 patients undergoing coronary artery bypass grafting (CABG) surgery. After induction of anaesthesia with fentanyl, propofol was infused continuously at a rate of 10 mg kg-1 h-1 for 20 min, and then the rate was reduced to 3 mg kg-1 h-1. Administration of heparin before cardiopulmonary bypass (CPB) did not affect total or unbound propofol concentration. Initiation of CPB decreased mean total propofol concentration from 2.6 to 1.7 micrograms ml-1 (P < 0.01). Simultaneously, mean unbound propofol concentration remained at 0.06 micrograms ml-1 because of a slight increase in the mean free fraction of plasma propofol (from 2.3 to 3.5%; P > 0.05). During hypothermic CPB, mean total propofol concentration increased to concentrations measured before bypass (to 2.1 micrograms ml-1; P > 0.05 vs value before CPB) and the mean unbound propofol concentration was at its highest (0.07 microgram ml-1; P < 0.05 vs value before heparin). After CPB and administration of protamine, the mean total propofol concentration remained lowered (1.7 micrograms ml-1; P < 0.05 vs value before heparin) and the mean unbound propofol concentration returned to the level measured before heparin (P < 0.001 vs value during hypothermia). The latency of the Nb wave from recordings of AEP increased after induction of anaesthesia, reached its maximum during hypothermia and was prolonged during the subsequent phases of the study. The latency of the Nb wave did not correlate with total or unbound propofol concentration. We conclude that the changes in total and unbound concentrations of plasma propofol were not parallel in patients undergoing CABG. During CPB or at any other time during the CABG procedure, the unbound propofol concentration did not decrease and Nb wave latency was prolonged compared with baseline values measured after induction of anaesthesia before the start of CPB.      

Effects of a single pre-operative dexmedetomidine dose on isoflurane requirements and peri-operative haemodynamic stability

In a double-blind, placebo-controlled study we investigated the effect of a single pre-induction intravenous dose of dexmedetomidine 2 μg.kg⁻¹ on anaesthetic requirements and peri-operative haemodynamic stability in 50 patients undergoing minor orthopaedic and general surgery. Patients were anaesthetised with nitrous oxide/oxygen/fentanyl, supplemented if necessary with isoflurane. The mean (SD) intra-operative isoflurane concentration was lower in the dexmedetomidine-treated patients than controls (0.01 (0.03)% compared to 0.1 (0.1)%; p = 0.001) although six of the 25 treated patients required isoflurane at some stage. The haemodynamic response to tracheal intubation and extubation was reduced in the dexmedetomidine group as was intra-operative heart rate variability; postoperative analgesic and anti-emetic requirements and peri-operative serum catecholamine concentrations were lower in the dexmedetomidine group. Hypotension and bradycardia occurred more frequently after dexmedetomidine.     

The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy.

The effects of two doses of dexmedetomidine (0.3 or 0.6 micrograms.kg-1), fentanyl 2.0 micrograms.kg-1, or saline as a single intravenous bolus administered 10 min prior to the induction of anesthesia were assessed in double-blind, randomized study in 96 women undergoing abdominal hysterectomy. In each patient, anesthesia was induced with thiopental 4.0 mg.kg-1, and after the effect of succinylcholine had dissipated, isoflurane 0.3% end-tidal concentration in 70% nitrous oxide was begun to maintain anesthesia. The isoflurane concentration was adjusted to maintain blood pressure and heart rate within 20% of preoperative values, and fentanyl was given if the end-tidal isoflurane concentration exceeded 1.5%. In all groups, blood pressure and heart rate increased after tracheal intubation. However, the increase in blood pressure and heart rate was significantly less in the higher dexmedetomidine (0.6 micrograms.kg-1) group than in the saline group (P less than 0.01). Also, the postintubation increase in heart rate was significantly less (P less than 0.05) in the dexmedetomidine 0.6 micrograms.kg-1 group (increase of 18 +/- 3 beats per min) compared to the fentanyl group (increase of 26 +/- 3 beats per min). In patients receiving dexmedetomidine 0.3 micrograms.kg-1, the increase in blood pressure or heart rate did not differ from that of the saline group. The mean end-tidal isoflurane concentration was significantly less in the women receiving the higher dose of dexmedetomidine (0.35%) than in those receiving saline (0.47%) or fentanyl (0.48%), although the reduction was not clinically important.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of the Minimum Alveolar Concentration of Isoflurane by Dexmedetomidine

Background: Alpha2-Adrenergic agonists have been shown to reduce anesthetic requirements of other anesthetics, and they may even act as complete anesthetics by themselves at high doses in animal models. The present study was designed to define the interaction of intravenous infusion of dexmedetomidine, an alpha2-adrenergic agonist, and isoflurane in patients having surgery by using the minimum alveolar concentration (MAC) of isoflurane as the measure of anesthetic potency.

Methods: Forty-nine women scheduled for abdominal hysterectomy were randomly allocated to receive either a placebo infusion (n = 16) or a two-stage infusion of dexmedetomidine with target plasma concentration of 0.3 ng/ml (n = 17) or 0.6 ng/ml (n = 16). The study drug infusion was commenced 15 min before induction of anesthesia with thiopental and alfentanil and was continued until skin incision. The end-tidal concentration of isoflurane for each patient was predetermined according to the "up-down" method of Dixon, and it was maintained for at least 15 min before the patient's response to skin incision was assessed.

Results: The MAC of isoflurane was 0.85% end-tidal in the control group, 0.55% end-tidal with the low dose of dexmedetomidine, and 0.45% end-tidal with the high dose of dexmedetomidine.     

Effect of bolus doses of alfentanil on the arousal response to intubation, as assessed by the auditory evoked response

We have studied the effect of bolus doses of alfentanil on the arousal response to intubation, using the auditory evoked response (AER) of the electroencephalogram (EEG) in 45 anaesthetized patients. After induction of anaesthesia with propofol and 20 min of positive pressure ventilation via a laryngeal mask airway with 0.6 MAC of isoflurane and 50% nitrous-oxide in oxygen, patients received saline (control), or alfentanil 15 or 50 micrograms kg-1 before intubation. The early cortical AER before and after intubation in each group was measured and compared. After intubation, Pa amplitude increased in the saline group by 60% (95% CI +10 to +130), decreased in the low-dose alfentanil group by 11% (-38 to +29) and decreased further in the high-dose alfentanil group by 26% (-49 to +7). There were significant (P < 0.005) linear trends in the three group means for Pa amplitude. Similarly, Nb latency increased in the saline group by 30% (-2 to +73), decreased in the low- dose alfentanil group by 10% (-32 to +19) and decreased further in the high-dose alfentanil group by 19% (-39 to +7). There were significant (P = 0.02) linear trends in the three group means for Nb amplitude. Systolic and diastolic arterial pressures increased after intubation in the control group, and to a lesser extent in the low-dose alfentanil group, but decreased after high-dose alfentanil. Heart rate increased after intubation in the control group but decreased in both alfentanil groups, decreasing to a greater degree in the high-dose group. There were significant (P < 0.001) linear trends for all three haemodynamic variables in the three groups. We conclude that the increase in Pa amplitude after intubation was blocked by bolus administration of alfentanil and that this effect was dose dependent.      

DEXMEDETOMIDINE ATTENUATES SYMPATHOADRENAL RESPONSES TO TRACHEAL INTUBATION AND REDUCES THE NEED FOR THIOPENTONE AND PEROPERATIVE FENTANYL

The effects of the new, highly selective alpha₂-adrenergic agonist,dexmedetomidine, were studied in a randomized, placebo-controlled,double-blind trial in 24 ASA I patients. Dexmedetomidine 0.6µg kg^–1 or saline was given i.v. 10 min before inductionof anaesthesia. The required dose of thiopentone was significantly(P < 0.001) smaller in the dexmedetomidine group (mean 4.4(SD 0.9) mg kg^–1) than in the control group (6.9 (1.6)mg kg^–1), and the drug attenuated the cardiovascular responsesto laryngoscopy and tracheal intubation. The concentration ofnoradrenaline in mixed venous plasma was smaller in the dexmedetomidinegroup during all phases of induction (P < 0.01). During surgery,fentanyl was required in a dose of 0.5 (0.6) mg kg^–1 and2.8(2.6) mg kg^–1 in the dexmedetomidine and control groups,respectively (P < 0.001). During 2h postoperative follow-up,oxycodone 0.06 (0.06) mg kg^–1 and 0.16 (0.1) mg kg^–1(P < 0.05) was given to the two groups respectively.     

右美托咪啶对异氟醚抑制切皮时患者体动反应的肺泡气最低有效浓度的影响

目的 探讨右美托咪啶对异氟醚抑制切皮时患者体动反应的肺泡气最低有效浓度(MAC)的影响.方法 择期全身麻醉下行上腹部手术患者,年龄40～60岁,ASA分级Ⅰ或Ⅱ级,体重指数22～27 kg/m2,采用随机数字表法,将患者随机分为3组:对照组(C组)、小剂量右美托咪啶组(D1组)和大剂量右美托咪啶组(D2组).麻醉诱导前静脉输注右美托咪啶(生理盐水稀释至15 ml)0.4 μg/kg(D1组)、0.8μg/kg(D2组)及生理盐水15 ml(C组),15 min内输注完毕.静脉注射芬太尼-异丙酚-琥珀酰胆碱麻醉诱导,气管插管后机械通气并开启异氟醚挥发罐.采用序贯法确定麻醉维持期间异氟醚的呼气末浓度,C组、D1组和D2组第1例患者异氟醚呼气末浓度分别设定为1.0%、0.8%和0.6%,当异氟醚呼气末浓度达到预设水平并维持15 min以上,且肌颤搐恢复到对照值90%以上时开始手术,相邻浓度差值为0.2%.于切皮时评估患者体动反应,以各交叉点异氟醚呼气末浓度的均数为MAC,并计算95%可信区间(CI).结果 C组、D1组和D2组入选病例分别为15、17和16例.异氟醚抑制切皮时体动反应的MAC及其95%CI分别为:C组(1.03±0.23)%(95%CI 0.83%～1.21%)、D1组(0.72±0.19)%(95%CI 0.58%～0.85%)、D2组(0.51±0.27)%(95%CI 0.30%～0.71%).与C组比较,D1组和D2组MAC降低(P＜0.01),D2组MAC明显低于D1组(P＜0.05).结论 右美托咪啶可明显降低异氟醚抑制切皮时患者体动反应的MAC,且与剂量有关.

Abstract：

Objective To investigate the effect of dexmedetomidine on minimum alveolar concentration (MAC) of isoflurane required to inhibit the body movement during skin incision. Methods Forty-eight ASA Ⅰ or Ⅱ patients aged 40-60 yr with body mass index of 22-27 kg/m2 undergoing elective upper abdominal surgery under general anesthesia were randomly divided into 3 groups: control group (group C, n = 15);low dose dexmedetomidine group (group D1, n = 17) and high dose dexmedetomidine group (group D2, n = 16). The patients were unpremedicated. Dexmedetomidine 0.4 and 0.8 μg/kg in normal saline (NS) 15 ml was infused over 15 min before induction of anesthesia in D1 and D2 groups respectively. Anesthesia was induced with fentanyl-propofol-succinylcholine. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained with isoflurane. MAC of isoflurane was determined by up-and-down technique. The initial end-tidal isofiurane concentration was set at 1.0%, 0.8% and 0.6% in C, D1 and D2 groups respectively. Each time the end-tidal isoflurane concentration was increased/decreased by 0.2%. Skin incision was made after 15 min of equilibration, when the twitch height returned to more than 90% of its control value. Movement of body and limbs including swallowing and coughing were carefully looked for when skin incision was made. MAC of isoflurane was the mean of end-tidal concentration of isoflurane of each crossover pair, and 95 % CI was calculated. Results MAC of isoflurane was significantly decreased in D1 and D2 groups as compared with group C and in group D2 as compared with group D1( P ＜ 0.05 or 0.01 ). Conclusion Dexmedetomidine can significantly decrease MAC of isoflurane required to inhibit the body movement during skin incision in a dose-dependent manner.     

DEXMEDETOMIDINE REDUCES INTRAOCULAR PRESSURE, INTUBATION REPONSES AND ANAESTHETIC REQUIREMENTS IN PATIENTS UNDERGOING OPHTHALMIC SURGERY

We studied the effects of a single i.v. dose of dexmedetomidine,a highly selective and specific alpha₂ adrenoceptor agonist,on intraocular pressure (IOP), haemodynamic and sympathoadrenalresponses to laryngoscopy and tracheal intubation, and on anaestheticrequirements in ophthalmic surgery. Thirty ASA I–II patientsundergoing cataract surgery were allocated randomly to receiveeither dexmedetomidine 0.6 µg kg^–1 or saline placeboi.v. 10 min before induction of anaesthesia in a double-blinddesign. After dexmedetomidine there was a 34% (95% confidenceinterval (Cl) 27–43%) reduction in IOP (P<0.001) and62% (Cl 57–68%) decrease in plasma noradrenaline concentrations(P<0.001). After intubation, maximum heart rate was 18% (Cl3–33%, P=0.036) and the maximum IOP 27% (Cl 11–43%.P=0.005) less in the dexmedetomidine group compared with thepatients treated with placebo. Within 10 min after intubation,maximum systolic and diastolic arterial pressures were alsosignificantly (P=0.013 and P=0.020) smaller in the dexmedetomidinegroup. The induction dose of thiopentone was smaller (23% (Cl20–26%) P=0.012), and the use of isoflurane or fentanylsupplements during anaesthesia was less frequent in the dexmedetomidinegroup. The patients premedicated with dexmedetomidine recoveredfaster from anaesthesia (P=0.042). These results suggest thatdexmedetomidine may be a useful anaesthetic adjunct in ophthalmicsurgery.     

Depressive effect of isoflurane anesthesia on motor evoked potentials

The influence of the volatile anesthetic isoflurane (Forane) on motor evoked potentials was examined in rats. To record motor evoked potentials, single-shock electrical stimulation was delivered to the forelimb representation of the motor cortex. This resulted in elicitation of a compound muscle action potential from the contralateral extensor muscles. The effect of isoflurane was examined at various concentrations ranging from 0.2 to 1.5%. With increasing concentrations of isoflurane there was a progressive increase in onset latency of the compound muscle action potential and a decrease in peak-to-peak amplitude and duration. Latencies were significantly increased over baseline values for concentrations of isoflurane from 0.5 to 1.5% (P values were 0.001 to 0.007). For the amplitude and the duration, responses at 0.5 to 1.5% isoflurane were significantly lower than baseline (P values were 0.001 to 0.007). We conclude that isoflurane anesthesia significantly changes the muscle response evoked by motor cortex stimulation in experimental animals.     

Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats

We have studied the effect of intrathecal administration of N-methyl-D- aspartate (NMDA) receptor antagonists on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after administration of a competitive NMDA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 micrograms), a non-competitive NMDA receptor antagonist, MK801 (0.1, 1.0, 10, 30 micrograms). NMDA (0.01, 0.1, 1.0, 10, 30 micrograms) and saline. APV at all doses except 0.01 micrograms decreased MAC by 17.1-32% (P < 0.001 and P < 0.0001). Although MK801 at 10 and 30 micrograms reduced MAC by 24.3-31.7% (P < 0.001 and P < 0.0001), lower doses did not affect MAC. Intrathecal administration of NMDA reversed these decreases in MAC, but not to control values with APV 10 and 30 micrograms and MK801 30 micrograms. We suspect that NMDA and NMDA receptor antagonists play important roles in the spinal cord in determining the MAC of isoflurane.      

Comparative assessment of the anaesthetic and analgesic effects of intramuscular and epidural clonidine in humans

Purpose

The aim of the study was to assess and compare in analogous controlled experimental conditions, the anaesthetic sparing and analgesic effects of the same dose of clonidine administered by the intramuscular (im) and epidural (ep) routes.

Methods

We used a randomized, double blind and placebo controlled protocol. Sixty patients undergoing abdominal hysterectomy were distributed into three groups who, 30 min before surgical incision, received: 300 μg ep clonidine plus im saline; ep saline plus 300 μg im clonidine; or ep and im saline (ss). General anaesthesia was maintained with 60% N₂O in O₂, and isoflurane administered at concentrations to maintain mean arterial pressure (MAP) and heart rate (HR) within 20% of basal values. Isoflurane requirements (mass spectrometry), cardiovascular variables (MAP, HR), and plasma concentrations of glucose, cortisol and prolactin were evaluated at critical time points. In the recovery room (RR), sedation (Ramsay) and pain intensity (VAS) were estimated at the time of analgesia request (TAR).

Results

Intramuscular and ep clonidine decreased isoflurane requirements similarly by about 85% (P < 0.001). Patients in the ep group had lower MAP (P < 0.03) and HR (P < 0.001) than in the im group, but im and ep clonidine similarly blunted the plasma prolactin increase induced by intubation. In RR, ep but not im clonidine (P < 0.01) induced postoperative analgesia demonstrated by a prolonged TAR 80.8 ± 7.3 (ep) 35.9 ± 3.2 (im) and 44.5 ±5.1 (ss) min and a lower VAS (P < 0.05).

Conclusions

Epidural and intramuscular clonidine decreased isoflurane requirements similarly, but only the epidural route provided postoperative analgesia, suggesting a spinal site for the analgesic action.     

右美托咪啶对异氟醚致新生鼠海马神经细胞凋亡的影响

【摘要】 目的 比较右美托咪啶(Dex)预处理给药和分次给药两种方法对异氟醚(Iso)致新生大鼠海马细胞凋亡的影响。方法 将出生后7天(postnatal day 7, P7)的SD大鼠随机分成6组:空气+盐水组(Air+NS组)、空气+Dex 25 μg·kg-1分次给药组(Air+Dex25×3组)、空气+Dex 75 μg·kg-1预处理组(Air+Dex75组)、异氟醚+盐水组(Iso+NS组)、异氟醚+ Dex 25μg·kg-1分次给药组(Iso+Dex25×3组)以及异氟醚+Dex 75μg·kg-1预处理组(Iso+Dex75组)。前3组吸入空气,后3组吸入0.75%异氟醚6 h。Air+NS组、Iso+NS组、Air+Dex75组和Iso+Dex75组在麻醉前20 min腹腔内注射生理盐水或75 μg·kg-1剂量的Dex;Air+Dex25×3组和Iso+Dex25×3组分别在麻醉前20 min,麻醉开始后2 h和4 h腹腔内重复注射25μg·kg-1剂量的Dex。麻醉结束后用原位末端标记(TUNEL)法检测海马神经细胞凋亡(n=4); 用Western blot检测海马激活型caspase-3蛋白表达变化(n=4)。 结果 异氟醚能诱导海马CA1区TUNEL阳性细胞数增加391.0 %(P<0.001);激活型caspase-3表达增加122.0%(P<0.001)。Iso +Dex25×3组和Iso+Dex75分别减少异氟醚诱导的TUNEL阳性细胞的增加为80.7%(P<0.001)和73.2%(P<0.001);两组均能完全抑制激活型caspase-3表达的增加(P<0.001);两组间无统计学差异(P>0.05)。结论 右美托咪啶预处理给药和分次给药都能通过抑制海马细胞凋亡来减轻异氟醚对新生大鼠的脑毒性作用,且两者的抗凋亡效果相似。     

Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy.

The usefulness of intravenous dexmedetomidine infusion for maintenance of anesthesia was studied in patients anesthetized with thiopental, fentanyl, nitrous oxide, and oxygen. Isoflurane was added as needed. The study was conducted in two parts, the first of which was an open dose-response study that comprised 14 women undergoing abdominal hysterectomy. After a suitable infusion regimen of dexmedetomidine was determined according to hemodynamic criteria, 20 patients were included in a double-blind, randomized placebo-controlled trial (10 receiving dexmedetomidine, 10 saline solution). Dexmedetomidine was administered as a two-step infusion to rapidly achieve a steady-state plasma concentration. The infusion was started with an initial dose given over 10 min before the induction of anesthesia; at induction the maintenance rate was begun and continued until closure of the abdominal fascia. The infusion regimens of dexmedetomidine tested in the dose-response study ranged from 120 ng.kg-1 x min-1, followed by 6 ng.kg-1 x min-1, to 270 + 13.5 ng.kg-1 x min-1. In the second part of the study, an initial infusion of 170 ng.kg-1 x min-1 was chosen, followed by 10 ng.kg-1 x min-1 for maintenance. Anesthesia was induced with thiopental (4.0 mg/kg) and maintained with isoflurane in 70% nitrous oxide and oxygen. Isoflurane was administered according to predetermined hemodynamic criteria. Dexmedetomidine infusion did not completely abolish the need for isoflurane but diminished its requirement by > 90% (P = 0.02). The heart rate response to endotracheal intubation was significantly blunted.     

Intravenous dexmedetomidine inhibits cerebrovascular dilation induced by isoflurane and sevoflurane in dogs.

Our aim in this study, performed using a closed cranial window preparation, was to investigate the effect of systemic pretreatment with dexmedetomidine on cerebrovascular response to isoflurane or sevoflurane. After instrumentation under pentobarbital anesthesia, 48 dogs were assigned to one of two groups: the isoflurane group or the sevoflurane group (n = 24 each). Twenty-four dogs received saline (n = 6) or one of three different doses of dexmedetomidine (0.5, 1.0, or 2.0 micrograms/kg) (n = 6 each) i.v. Animals were then exposed to three different minimum alveolar anesthetic concentrations (MACs; 0.5, 1.0, and 1.5) of either isoflurane or sevoflurane. Cerebrovascular diameters were measured at each stage. Pretreatment with dexmedetomidine decreased pial vessel diameters. Both isoflurane and sevoflurane significantly dilated both arterioles and venules in a concentration-dependent manner. Isoflurane- and sevoflurane-induced dilation of cerebral arterioles was significantly attenuated in the presence of dexmedetomidine. The dexmedetomidine-induced attenuation of the vascular responses was not dependent on the dose of dexmedetomidine and was not different between isoflurane and sevoflurane. The vasodilation of cerebral pial vessels induced by isoflurane and sevoflurane could be attenuated by the systemic administration of dexmedetomidine, and this interaction between dexmedetomidine and volatile anesthetics showed no evidence of dose-dependency. Implications: The systemic administration of dexmedetomidine attenuates the dilation of cerebral vessels induced by isoflurane and sevoflurane in pentobarbital-anesthetized dogs. This interaction was not dependent on the clinical (0.5-2.0 micrograms/kg) dose of dexmedetomidine and was not different between isoflurane and sevoflurane anesthesia.     

Volatile anesthetics excite mammalian nociceptor afferents recorded in vitro

The present study investigated the actions of halothane, isoflurane, and enflurane on spontaneous discharge and evoked action potential activity in mammalian A-delta and C fiber nociceptors from the in vitro rabbit cornea. At 1 MAC halothane, isoflurane, and enflurane significantly (P less than 0.001) increased spontaneous discharge frequency of C fibers to 410%, 388%, and 569% of control, respectively. The anesthetics produced burst discharge activity over the concentration range of 0.25-1.5 MAC and depressed discharge activity at higher concentrations (greater than 3.0 MAC). Similar excitatory effects were produced by the potassium channel blocker 4-aminopyridine (250-500 microM). Variable effects on evoked discharge activity of A-delta fibers were observed. Halothane reduced action potential amplitude (77.3 +/- 4.5% of control +/- SD; n = 6 at 1 MAC) and increased spike latency (0.42 +/- 0.075 ms). In contrast, the ethers decreased both spike latency (isoflurane by 0.31 +/- 0.064 ms and enflurane by 0.35 +/- 0.058 ms) and action potential amplitude. Halothane and the ether anesthetics produced a common excitatory action on C fibers; however, the differential depressant effects on A-delta fibers suggest that different membrane mechanisms of action are involved.     

右美托咪啶-异丙酚-芬太尼复合麻醉对颈椎手术病人体感诱发电位及运动诱发电位的影响

目的 评价右美托咪啶-异丙酚-芬太尼复合麻醉对颈椎手术病人体感诱发电位及运动诱发电位的影响.方法 择期全麻下行颈椎手术的病人36例,随机分为2组(n=18):异丙酚-芬太尼复合麻醉组(C组)和右美托咪啶-异丙酚-芬太尼复合麻醉组(D组).麻醉诱导:TCI异丙酚,血浆靶浓度为2μg/ml,静脉注射芬太尼1～2μg/kg,意识消失后经口置入喉罩进行通气.意识消失后D组经10 min静脉注射右美托咪啶0.5μg/kg,随后以0.5μg·kg-1·h-1的速率静脉输注至术毕,C组给予等容量生理盐水.分别于给予右美托咪啶前及静脉输注右美托咪啶10 min时记录体感诱发电位P15-N20波的波幅和潜伏期,并记录运动诱发电位的未引出情况.结果 与C组比较,D组P15-N20波的波幅和潜伏期差异无统计学意义(P＞0.05);两组运动诱发电位未引出率均为0.结论 右美托咪啶-异丙酚-芬太尼复合麻醉对颈椎手术病人体感诱发电位及运动诱发电位无影响.     

Effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects

BACKGROUND: Dexmedetomidine, a selective alpha2-adrenoceptor agonist, has counteracting effects on the cardiovascular system. It mediates sympatholysis by activating alpha2 adrenoceptors in the central and peripheral nervous system, and vasoconstriction and vasorelaxation by activating postsynaptic alpha2 adrenoceptors in blood vessels. The goal of this study was to determine the effects of therapeutic and high concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy subjects. METHODS: The authors studied 12 healthy young men. Myocardial blood flow (assessed with positron emission tomography), myocardial function (by echocardiography), and hemodynamic data were collected before and during low (measured mean plasma concentration, 0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine. RESULTS: The low concentration of dexmedetomidine reduced myocardial perfusion (mean difference, -27% from baseline [95% confidence interval, -31 to -23%], P < 0.001) in parallel with a reduction in myocardial oxygen demand (estimated by the rate-pressure product (-23% [-28 to -18%], P < 0.001). The high dexmedetomidine plasma concentration did not further attenuate myocardial perfusion (-3% [-12 to +6%] from low dexmedetomidine, P > 0.05; -29% [-39 to -18%] from baseline, P < 0.001) or statistically significantly affect the rate-pressure product (+5% [0 to +10%], P > 0.05). Systolic myocardial function was attenuated by sympatholysis during the low infusion rate and was further attenuated by a combination of the sustained sympatholysis and increased afterload during the high infusion rate. CONCLUSIONS: In healthy subjects, plasma concentrations of dexmedetomidine that significantly exceed the recommended therapeutic level do not seriously attenuate myocardial perfusion below the level that is observed with usual therapeutic concentrations and do not induce evident myocardial ischemia.