Tryba M, Wruck G
Universitätsklinik für Anaesthesiologie, Intensiv- und Schmerztherapie, Berufsgenossenschaftliche Krankenanstalten, Bergmannsheil, Ruhr-Universität Bochum.
Anaesthesist. 1989 May;38(5):251-4.
Many drugs potentiate the action of non depolarizing relaxants. These interactions are of clinical importance if such drugs are administered during the perioperative period. H2 Antagonists are increasingly often used for premedication. Cimetidine inhibits the elimination of a number of drugs used in the perioperative period. We therefore investigated whether H2 antagonists enhanced neuromuscular blockade by vecuronium, a medium short acting non depolarizing muscle relaxant. METHODS. The study was carried out in 24 female patients (ASA class I or II) scheduled for microsurgical procedures. Neuromuscular transmission was recorded electromyographically using four stimulations every 20 s to the ulnar nerve. After induction with thiopentone, anesthesia was maintained with fixed concentrations of volatile anesthetics. Fentanyl was administered for additional analgesia. Vecuronium was used as the sole muscle relaxant. Fixed repetitive doses of vecuronium (0.8-1.2 mg) were injected whenever the T1 returned to 25%. This time interval was defined as the T1-25 period. The study proper started when the T1-25 period had stabilized. After two control periods, six patients in each group received either 200 or 400 mg cimetidine or 100 mg ranitidine. The fourth group was the control group. The T1-25 periods and the maximal EMG depression were recorded automatically for at least two further periods. The first measured period was recorded as 100% and the length of each other periods was calculated as a percentage of the control period. This method enables an intraindividual comparison of the length of the T1-25 period and the maximal EMG depression before and after administration of the H2 antagonists. A two-tailed Student's t-test was used to test statistical significance, P less than 0.05 being accepted as significant. RESULTS. In the control group and in the group with 200 mg cimetidine or 100 mg ranitidine no statistical significant prolongation of the T1-25 period or of the maximal EMG depression could be observed, while after 400 mg cimetidine there was significant prolongation (mean 161 +/- 14.8%) of the T1-25 period and significantly greater EMG depression compared with the pre-cimetidine values. In the groups with 200 mg cimetidine or 100 mg ranitidine few patients showed prolongation of the T1-25 period up to 130%. DISCUSSION. Our results confirm experimental studies that have shown cimetidine to enhance aminoglycoside--relaxant interactions. Because we found an immediate response to the administration of the H2 antagonists, the interaction cannot be on the elimination side; it must be at the neuromuscular junction. Experimental investigation has shown that calcium reverses the cimetidine effects. It is therefore probable that the cimetidine--relaxant interaction occurs at the presynaptic level. Careful observation seems to be necessary if H2 antagonists, especially cimetidine, are administered intraoperatively at the same time as drugs that also enhance
许多药物可增强非去极化肌松药的作用。如果在围手术期使用这些药物，这些相互作用具有临床重要性。H2拮抗剂越来越常用于术前用药。西咪替丁可抑制多种围手术期使用药物的消除。因此，我们研究了H2拮抗剂是否会增强维库溴铵（一种中短效非去极化肌松药）的神经肌肉阻滞作用。方法。该研究在24例计划进行显微外科手术的女性患者（ASA I或II级）中进行。通过每隔20秒对尺神经进行四次刺激，以肌电图记录神经肌肉传递。用硫喷妥钠诱导后，用固定浓度的挥发性麻醉药维持麻醉。给予芬太尼以增强镇痛效果。维库溴铵用作唯一的肌松药。每当T1恢复到25%时，注射固定重复剂量的维库溴铵（0.8 - 1.2毫克）。该时间间隔定义为T1 - 25期。当T1 - 25期稳定后开始正式研究。经过两个对照期后，每组六名患者分别接受200毫克或400毫克西咪替丁或100毫克雷尼替丁。第四组为对照组。至少在另外两个时期自动记录T1 - 25期和最大肌电图抑制情况。第一个测量期记录为100%，其他各期的长度计算为对照期的百分比。该方法能够对给予H2拮抗剂前后的T1 - 25期长度和最大肌电图抑制进行个体内比较。采用双侧Student t检验来检验统计学显著性，P值小于0.05被认为具有显著性。结果。在对照组以及接受200毫克西咪替丁或100毫克雷尼替丁的组中，未观察到T1 - 25期或最大肌电图抑制有统计学显著性延长，而在给予400毫克西咪替丁后，T1 - 25期有显著延长（平均161±14.8%），并且与给予西咪替丁前的值相比，肌电图抑制显著更大。在接受200毫克西咪替丁或100毫克雷尼替丁的组中，少数患者的T1 - 25期延长至130%。讨论。我们的结果证实了实验研究，该研究表明西咪替丁可增强氨基糖苷类 - 肌松药的相互作用。因为我们发现给予H2拮抗剂后有即时反应，所以这种相互作用不可能在消除方面；它一定发生在神经肌肉接头处。实验研究表明钙可逆转西咪替丁的作用。因此，西咪替丁 - 肌松药的相互作用很可能发生在突触前水平。如果术中同时给予H2拮抗剂，尤其是西咪替丁，以及其他也增强……的药物，似乎有必要进行仔细观察。
