离体模式下地氟醚、异氟醚和氟烷通过氧合器应用的药代动力学研究

目的研究在离体模式下地氟醚、异氟醚和氟烷通过氧合器应用的药代动力学。方法选择成人型膜式氧合器，预充生理盐水2000ml，连接动静脉端形成环路。将预先配制在钢瓶内的2．4％地氟醚、0．46％异氟醚及0．308％氟烷混合气体输送至氧合器，气体流量3Umin，泵流量4Umin，温度30℃。在摄入及排出的0、1、2、4、8、16、32min采集氧合器入气口、排气口及动脉端样本，测定吸入麻醉药分压。结果在摄入阶段及排出阶段，动脉端溶液中三种吸入麻醉药分压迅速上升或下降，用药后8min时，三种药物的动脉端样本分压与吸入气分压之比(Pa／Pi)均达50％以上，停药后8min动脉端样本分压与动脉端样本分压峰值之比(Pa／Pa0)均降至10％以下。三种药物之间在同一时间点Pa／Pi及Pa／17aO均有显著性差异(P＜0．05)。各吸入麻醉药动脉端样本与氧合器排气口中分压之间呈线性相关关系(r=0．99)。结论(1)Bentley膜式氧合器具有快速转运吸入麻醉药的性能；(2)地氟醚、异氟醚及氟烷通过氧合器应用后摄取和排出速率随着药物的水／气分配系数的增高而减慢；(3)通过监测氧合器排气口中吸入麻醉药分压可以快速、准确地估计液相中吸入麻醉药分压。     

氟烷吸入麻醉引起c—fos基因在中枢神经系统的表达与分布

研究氟烷吸入麻醉在中枢神经系统作用部位。应用ｃ－ｆｏｓ基因免疫组织化学方法。ＳＤ大鼠在吸入氟烷浓度为０．７５％．１。５％和２％麻醉１ｈ后，Ｆｏｓ阳性神经元主要分布于端脑；梨状皮层，杏仁核簇，伏核，外侧隔核，终纹麻核、海马ＣＡＩ区，海马回嗅觉小岛；     

Cardiac arrhythmogenic action of benzo(a)pyrene in the rabbit

Rabbits treated with benzo(a)pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene and 3-methylcholanthrene both increased the metabolism of trichloroethylene, but 3-methylcholanthrene did not increase its cardiotoxic effect. The basis of the arrythmogenic action of benzo(a)pyrene appears to be unrelated to its ability to induce xenobiotic metabolism.     

Effect of temperature variation (22˚C- 44˚C) on halothane and caffeine contracture testing in normal humans

Background: Malignant hyperthermia (MH) susceptibility is diagnosed using halothane-caffeine contracture testing of a muscle sample maintained at 37˚C. However, there has not been a systematic study that examines the effect of different temperatures on the response of normal muscle to halothane and caffeine. We hypothesized that altering bath temperature would modify the contracture responses.
Methods: We obtained muscle samples from 20 patients undergoing surgical procedures of the lower extremities. The samples were dissected into 245 bundles and the bundles were exposed to halothane 3% or incremental caffeine, according to the North American MH group protocol. Several bundles from each patient were simultaneously studied at four different temperatures (22˚C, 30˚C, 37˚C and 44˚C). Each bundle was studied at only one temperature, the muscle samples of 3 patients were simultaneously studied at all four temperatures for halothane and caffeine.
Results: Maximum contracture to caffeine (32 mM) was highest at 37˚C; however, at lower caffeine concentrations (2–4 mM), there was no consistent effect of temperature on contracture response. Likewise, temperature did not alter contracture responses to halothane. The extremes of temperature (22˚C and 44˚C) were associated with lack of twitch in response to electrical stimulation. For the bundles exposed to halothane at 22"C, the absence of a twitch was associated with the presence of a contracture, although these were never above the diagnostic threshold.
Conclusions: We conclude that temperature has little effect on responses of normal muscle to halothane and caffeine.     

Evaluation of awakening and recovery characteristics following anaesthesia with nitrous oxide and halothane fentanyl or both for brief outpatient procedures in infants

This study compared recovery characteristics and postoperative ventilatory function when halothane, fentanyl or combination of halothane and fentanyl in addition to N₂O were used for intraoperative anaesthesia in term infants undergoing hernia repair as outpatients. Sixty-six full term ASA PS I infants ages 1–12 months were studied. All received inhalation induction with N₂O, O₂ and halothane, followed by intravenous atropine and atracurium, tracheal intubation, and controlled ventilation. For anaesthesia maintenance, patients were randomized into one of three groups. Group I received 70% N₂O, 30% O₂ and halothane. Group II received 70% N₂O, 30% O₂, halothane and 2 μg·kg^?1 fentanyl. Group III received 70% N₂O, 30% O₂ and 10 μg·kg^?1 fentanyl. Awakening times were similar in all three groups, however, Group I patients had significantly shorter recovery and discharge times than those of Group II and III. None of the patients experienced postoperative apnoea or periodic breathing. One patient in Group III experienced two brief episodes of bradycardia not associated with apnoea or arterial desaturation (Spo ₂ >90% for greater than 30 s). Decreased Spo ₂ occurred less frequently in Group I (5.9%) compared to Group II (22.7%) and Group III (19.0%) patients, however, the group differences were not significant. Transcutaneous CO₂ (TcCO₂) values were not statistically different among the three groups. Pain scores were initially lower in Groups II and III, but at 120 min the differences were not significant. Postoperative apnoea was not observed in this study. Spo ₂ <90% and TcCO₂ >9 kPa (70 mmHg) was more common in infants receiving 2 and 10 μg·kg^?1 fentanyl than in infants receiving halothane and nitrous oxide anaesthesia. Infants <3 months old did not have a higher incidence of Spo ₂ <90% or significantly higher TcCO₂ values when compared to infants >3 months old. Fentanyl in doses used in this study did not prolong awakening time but did prolong recovery and discharge times in outpatient infants.     

Different effects of halothane, isoflurane and sevoflurane on sarcoplasmic reticulum of vascular smooth muscle in dog mesenteric artery

Background: The direct effect of halothane on vascular smooth muscle is mediated in part via its effects on the sarcoplasmic reticulum (SR). Little information is available concerning the effects of other volatile anesthetics including isoflurane and sevoflurane, whose vascular effects differ from those of halothane. The aim of the present study was to compare the effects of halothane, isoflurane and sevoflurane on the SR by testing the contraction induced by caffeine in vascular smooth muscle. Methods: Rings without endothelium from isolated canine mesenteric artery were mounted in physiological saline solution (PSS) for isometric tension recording. After complete depletion of Ca²⁺ from the SR by adding 35 mM caffeine, the rings were exposed to normal Ca²⁺ containing PSS (Ca²⁺ loading), to Ca²⁺-free PSS for 10 min, and then to 15 mM caffeine to induce contraction. Anesthetics were administered during Ca²⁺ loading, the Ca²⁺-free phase and simultaneously with caffeine administration. Results: Halothane (0.5-2%) attenuated the caffeine-induced contraction of canine mesenteric artery when administered during Ca²⁺ loading in the SR (P<0.001), whereas isoflurane and sevoflurane (1–4%) failed to affect the contraction. When given simultaneously with caffeine, halothane (1–2%) potentiated the caffeine-induced contraction (P<0.05), but isoflurane and sevoflurane had no effect. When given before caffeine administration, halothane (0.5-2%), isoflurane (24%) and sevoflurane (4%) all potentiated the caffeine-induced contraction (P<0.05). Conclusion: It has been shown that halothane not only potentiates caffeine- induced Ca²⁺ release from the SR, but also induces contraction by releasing Ca²⁺ from the SR. We conclude that halothane decreases Ca²⁺ accumulation in the SR while exerting facilitative and additive effects on caffeine-induced Ca²⁺ release from the SR when applied before caffeine administration and simultaneously with caffeine, respectively, whereas isoflurane and sevoflurane lack both the ability to decrease Ca²⁺ accumulation and an additive effect on caffeine-induced Ca²⁺ release from the SR, but are able to facilitate Ca²⁺ release by caffeine.     

In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: Results of testing patients surviving fulminant MH and unrelated low-risk subjects

Background: Determination of sensitivity and specificity of the in vitro contracture test (IVCT) for malignant hyperthermia (MH) susceptibility using the European MH Group (EMHG) protocol has been performed in some laboratories but only on a small sample from the combined EMHG. Thus, the purpose of the present study was to determine combined EMHG sensitivity and specificity of the test. Methods: Results of IVCT of patients with previous fulminant MH and normal, low-risk subjects (controls) were collected from 22 centresof the EMHG. IVCT was performed according to the EMHG protocol. Patients were included inthe study if the clinical crisis had a score of at least 50 points with the Clinical Grading Scale. Low-risk subjects were included provided they did not belong to a family with known MH susceptibility, they had not developed any signs of MH at previous anaesthetics, and they did not suffer from any neuromuscular disease. For inclusion of both MH patientsand low-risk subjects, at least 1 muscle bundle in the IVCT should have twitches of 10 mN(1 g) or more. For evaluation of individual tests, only muscle bundles with twitch heights of 10 mN (1 g) or more were used. Results: A total of 1502 probands had undergone IVCT because of a previous anaesthesia with symptoms and signs suggestive of MH. Of these, 119 had clinical scores of 50 and above. From these 119 MH-suspected patients and from 202 low-risk subjects, IVCT data were collected. Subsequently, 14 MH-suspected patients were excluded from further analysis for thefollowing reasons: In 3 patients, the suspected MH episode could be fully explained by diseases other than MH; in 11 MHS patients, IVCT was incomplete (n=l), data were lost (n=3), or none of the muscle bundles fulfilled twitch criteria (n=7). Of the remaining 105 MH-suspected patients, 89 were MHS, 10 MHEh, 5 MHEc, and one MHN. Thus, we observed a diagnostic sensitivity of the IVCT of 99.0% if the MHE group is considered susceptible(95% confidence interval 94.8–100.0%). Of the 202 low-risk subjects, 3 were MHS, 5 MHEh, 5 MHEc, and 189 MHN. This gives a specificity of the IVCT of 93.6% (95% confidence interval 89.2–96.5%). Conclusion: The IVCT for diagnosis of MH susceptibility in Europe has a high sensitivity and a satisfactory specificity.     

A Pilot Study: Defibrillation Thresholds in Dogs are Similar with Isoflurane, Halothane, and Pentobarbital

The objective of this pilot study was to determine if three common anesthetic drugs have differing effects on the measurement of defibrillation thresholds (DFT) in dogs. The drugs compared were pentobarbital, isoflurane, and halothane. We used six dogs, which were surgically instrumented, in a chronic study design. Each dog had two internal defibrillation patches placed on its heart, which were used to deliver the defibrillation energy. DFT was determined while each dog was anesthetized under each of the listed drugs in a crossover design. This pilot study suggests that differences in DFT due to the anesthetic drugs is not significant in studies with low numbers of animals (halothane 14.5 ± 1.0, isoflurane 14.2 ± 1.0, pentobarbital 12.8 ± 1.0;P = NS; mean ± SE). Tbe variation in DFT between individual animals is much larger than the difference in DFT due to the drugs.     

Age, fiber type composition and in vitro contracture responses in human malignant hyperthermia

Muscle fiber typing and in vitro contracture tests were performed in 59 patients investigated for susceptibility to malignant hyperthermia (MH). Eighteen patients were found to be susceptible to MH. There was no difference in age or fiber type distribution between MH susceptible and non-susceptible patients. No correlation was found between age and fiber type distribution. Separate analyses for each diagnostic group revealed no relationship between age or fiber type distribution and response to halothane or caffeine. When all caffeine results were pooled, however, there was a significant effect of age on the caffeine specific concentration (the concentration eliciting a contracture of 1 g), but not on the caffeine threshold concentration (the minimal concentration eliciting an increase in tension). It is concluded that age and fiber type distribution have no influence on MH diagnosis, if the protocol of the European MH Group for evaluation of susceptibility to MH is followed.     

The onset of ablation of the evoked adductor pollicis muscle twitch in children: a clinical perspective

The time to loss of the adductor pollicis muscle response to ulnar nerve stimulation at 1 Hz (twitch) after succinylcholine, 1.5 mg.kg-1 intravenously (IV), or vecuronium, 0.1 mg.kg-1 (IV), administration was assessed visually in 134 children, age 2-13 yr, during clinically determined, deep halothane, enflurane and isoflurane anaesthesia. The overall time to twitch ablation and duration of succinylcholine's action is in agreement with published times obtained under controlled experimental conditions; the onset time following vecuronium is comparable to those observed during a similar anaesthetic background measured under controlled experimental conditions. Twitch ablation after succinylcholine was achieved in half the time needed following vecuronium regardless of anaesthetic agent. Succinylcholine's and vecuronium's onset time as well as succinylcholine's duration is adequately assessed by the outlined, simple clinical means. The choice of inhalation agent does not affect the time to visible twitch ablation in a clinically relevant manner; nor does it make an appreciable difference, in clinical terms, in succinylcholine's duration of action.