Vecuronium induced neuromuscular blockade

The speed of onset of neuromuscular blockade was measured for increasing doses of vecuronium. Onset times were found to be shorter with larger doses, up to a limit of ED95 X 3 (0.15 mg/kg). Thereafter, increasing the dose, even up to ED95 X 8 (0.4 mg/kg), did not appreciably shorten the time to full neuromuscular blockade. The clinical implications of, and pharmacokinetic basis for, these findings are discussed.     

The effect of acutely administered phenytoin on vecuronium-induced neuromuscular blockade

Phenytoin was administered intravenously in a dose of 10 mg kg to a group of patients in whom steady state neuromuscular blockade had been established with an infusion of vecuronium. A control group of patients were given 0.9% saline instead of phenytoin. Administration of phenytoin produced significant augmentation of neuromuscular blockade (p less than 0.001). The possible mechanism of this effect is discussed.     

Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade

The effect of epidurally administered bupivacaine on duration, intensity and reversal characteristics of atracurium-induced neuromuscular blockade was studied in 30 healthy patients anaesthetized with thiopentone, fentanyl, midazolam and nitrous oxide. Fifteen patients received, in addition, epidural anaesthesia with bupivacaine. The remaining patients served as controls. The ulnar nerve was stimulated at the wrist and the evoked twitch response from the adductor pollicis was measured with a force displacement transducer. Neuromuscular blockade was induced with atracurium 0.5 mg i.v. and maintained with repeated doses of atracurium 0.15 mg/kg whenever the twitch height had recovered to 15% of the initial twitch height. After operation, the neuromuscular blockade was reversed with neostigmine when the twitch height had recovered to 15%. In the epidural group the clinical duration of neuromuscular blockade, time until first response to train-of-four (TOF) and reversal time were all significantly prolonged (P less than 0.05). Post-tetanic count (PTC) after 20 min was also significantly lower in the epidural group (P less than 0.05). It is therefore concluded that epidurally administered bupivacaine prolongs atracurium-induced neuromuscular blockade. The clinical implication of the modest prolongation is, however, limited.     

The effect of a priming epidural injection of adrenaline on epidural blockade with bupivacaine

Twenty-four patients receiving epidural anaesthesia were studied to test the hypothesis that 1:200,000 adrenaline administered into the epidural space 5 minutes before 20 ml bupivacaine 0.5% would improve nerve block and delay systemic absorption of the local anaesthetic. Group A/B received 20 ml adrenaline 1:200,000 5 minutes before 20 ml bupivacaine 0.5%, group S/BA 20 ml saline followed by 20 ml bupivacaine 0.5% with 100 micrograms adrenaline, and group S/B saline 20 ml followed by 20 ml plain bupivacaine 0.5%. Mean maximum plasma concentrations of bupivacaine tended to be lower in the adrenaline groups. A delay in the time to peak plasma concentration of bupivacaine was noted in the A/B group; this indicated that priming with adrenaline may be effective at delaying early systemic uptake of the local anaesthetic. In both adrenaline groups a more prolonged epidural block and increased efficacy were noted, although this was only significant for the duration of block at T6 (p = 0.023) and duration of motor block at Bromage level 1 (p = 0.016) in group A/B. There seems little clinical advantage in administering adrenaline 5 minutes before bupivacaine.     

Respiratory function in children during recovery from neuromuscular blockade

Residual neuromuscular blockade is a major risk factor for respiratory insufficiency. We examined the relationship between neuromuscular and respiratory function in 18 ASA I or II children aged 2–4 years. Lung function was measured by pneumotachography and transpulmonary pressure, neuromuscular transmission by first twitch response ratio (T1:T1) and train-of-four ratio (TOFR), before and at specific points in recovery from vecuronium paralysis. The tidal volume was directly related to maximal inspiratory pressure at occlusion ( P _Iocc), P <0.001, whereas the minute ventilation (V_E) was related to the respiratory drive (P0.1), P <0.001. The best predictors of minute ventilation were the P0.1 ( r =0.57), and the TOFR ( r =0.62). P _Iocc and P0.1 correlated closely ( r =0.889, P =0.002) but TOFR and T1:T1 did not correlate with either. Our results show that the occlusion pressure measurements, P0.1 and P _Iocc, were good predictors of both V_E·kg⁻¹ and respiratory work.     

Onset and recovery of neuromuscular blockade after two doses of rocuronium in children

Study Objective: To determine if 450 μg/kg (1.5 times the ED₉₅) of rocuronium would result in a comparable onset with a shorter duration of action when compared with 600 μg/kg (2 times the ED₉₅).

Design: Randomized, single-blind study.

Setting: Teaching hospital.

Patients: 85 ASA physical status I and II children ages 2 through 12, undergoing elective surgery with an inhalation induction using halothane.

Interventions: Group 1 received 600 μg/kg rocuronium, and Group 2 received 450 μg/kg rocuronium.

Measurements and Main Results: The two groups were compared using a Student’s t-test, with p < 0.05 significant. The time of onset, or time to 95% suppression of neuromuscular twitch with standard errors, was 140 ± 13 seconds (range 46 to 365 sec) in Group 1 and 148 ± 13 seconds (range 82 to 345 sec) in Group 2 (NS = not significant). The times to 25% return of twitch from baseline (T₂₅) in Groups 1 and 2 were 28 ± 1.5 minutes (range 14 to 45 min) and 26 ± 1.6 minutes (range 10 to 55 min), respectively (NS). The differences between these two doses in onset of, and recovery from, block were not found to be statistically significant. The results, however, excluded 5% of the higher dose group and 31% of the lower dose group who did not achieve 95% suppression of twitch. Time to maximal suppression of neuromuscular blockade, however, was not statistically significant for the 85 patients with a time of 270 ± 28 seconds (range 91 to 605 sec) with a mean maximal suppression of 98.7% in Group 1 and 313 ± 25 seconds (range 91 to 899 sec) with a mean maximal suppression of 93.1% in Group 2.

Conclusion: The two doses of rocuronium did not differ statistically in onset or duration. Rocuronium at 600 μg/kg offers more reliability than 450 μg/kg in achieving adequate muscle relaxation, and the lower dose may result in a significantly large number of patients who may have inadequate intubating conditions.     

罗哌卡因与丁哌卡因硬膜外麻醉剖宫产的药效学比较

目的 将新型酰胺类局部麻醉药罗哌卡因的的药效学与丁哌卡因进行比较。方法 选择行择期剖宫产的产妇２０例,分成两组进行硬膜外麻醉。随机在硬膜外注入０．７５％罗哌卡因。对镇平面及达到最高平面和最低平面所用时间,运动阻滞程度及恢复时间,术中镇痛效果,新生儿Ａｐｇａｒ评分,不良反应的发生情况,血压和心率的变化进行观察。．     

氯普鲁卡因、布比卡因和罗哌卡因在下肢手术腰-硬联合麻醉中的比较

目的比较氯普鲁卡因、布比卡因和罗哌卡因在下肢手术腰-硬联合麻醉(CSEA)中的应用效果。方法择期行髋关节及以下部位手术患者300例,随机均分成三组:氯普鲁卡因组(C组)、布比卡因组(B组)和罗哌卡因组(R组),蛛网膜下腔分别给予1.5%氯普鲁卡因、0.5%布比卡因和0.5%罗哌卡因各2 ml。记录患者感觉阻滞起效时间、平面固定时间、阻滞平面、腰麻持续时间和运动阻滞效果。结果 C组阻滞平面固定时间、腰麻持续时间明显短于B、R组(P<0.05)。C组感觉阻滞起效时间短于B组,但长于R组(P<0.05)。C组最高阻滞平面明显高于B、R组(P<0.05)。结论与0.5%罗哌卡因和0.5%布比卡因比较,1.5%氯普鲁卡因具有起效快、阻滞完善和运动阻滞效果弱的特点,小剂量氯普鲁卡因可用于手术时间较短的CSEA中的脊麻。     

Reversal of profound paralysis: use of large doses of edrophonium to antagonize vecuronium and pancuronium induced neuromuscular blockade

The ability to evoke reversal of dense vecuronium- and pancuronium-induced paralysis (T1 10% of control) with edrophonium 1.0 mg.kg-1 was studied using train-of-four nerve stimulation and electromyographic monitoring. Two different end-points, train-of-four ratios of 0.5 and 0.7, were used to define "adequate reversal", and the results for both relaxants were compared. Reversal was reliable and rapid for vecuronium if either ratio was used with times of 2.8 (1.5) and 9 (3) min required to achieve ratios of 0.5 and 0.7, respectively. However, if the block was due to pancuronium, reversal was unreliable with 2 of 9 and 4 of 9 patients not achieving ratios of 0.5 and 0.7, respectively. Reversal was also markedly prolonged in this group with a mean time of 37 (23) min to achieve a ratio of 0.7, and in almost half these patients a supplementary dose of edrophonium was required.     

腰硬联合麻醉剖宫产术中布比卡因剂量的临床进展

布比卡因腰硬联合麻醉(combined spinal-epidural anesthesia,CSEA)在剖宫产中的应用较多,但其腰麻用于剖宫产术的最佳剂量较难确定,通过阅读文献发现有4种方法分别为给予小剂量腰麻,把腰麻限制在低位节段,通过硬膜外追加利多卡因来加强麻醉效果;根据身高与体重调节腰麻的剂量;通过硬膜外注射盐水来减少腰麻剂量;通过布比卡因腰麻复合阿片类药物来减少腰麻剂量,可使母体血液动力学相对稳定,副作用发生率低,麻醉效果好,但在这4种给药方法中,究竟哪一种能使剖宫产患者血液动力学最稳定、麻醉效果最好、副作用最少,还有待于进一步研究.     

Transpulmonary disposition of prilocaine, mepivacaine, and bupivacaine in humans in the course of epidural anaesthesia

The pulmonary first-pass kinetics of the amide-linked local anaesthetics prilocaine, mepivacaine and bupivacaine were studied in 33 patients after a single epidural injection. Drug concentrations were monitored before and after lung passage, i.e. in samples withdrawn simultaneously from mixed venous and arterial blood. In most cases, maximum plasma concentrations were observed 10 min after injection (range 2 to 30 min). Two min after injection the local anaesthetics were distinctly extracted by the lung (prilocaine 40%, mepivacaine 20%, and bupivacaine 12%). Prilocaine was retained by the lung more effectively than bupivacaine and mepivacaine. However, a transpulmonary concentration gradient could be observed only for a short time, i.e. maximum 15 min. Altogether, in the case of accidental fast absorption, e.g. inadvertent intravenous injection, arterial peak concentrations of these drugs will be attenuated by passage of the lung. However, the lung will not substantially lower the risk of toxicity by amide-linked local anaesthetics during normal conditions of regional anaesthesia where slow absorption occurs.     

罗哌卡因与布比卡因用于硬膜外阻滞麻醉效果的Meta分析

目的 评价罗哌卡因在硬膜外阻滞麻醉应用中的效果与安全性. 方法 检索PubMed、中国学术期刊全文等数据库中罗哌卡因与布比卡因在硬膜外阻滞麻醉的对比研究,利用Meta分析专用软件RevMan 5.0进行系统评价,重点分析罗哌卡因与布比卡因在感觉阻滞起效时间、运动阻滞恢复时间以及低血压发生率间的差异. 结果 12项研究纳入Meta分析,其中罗哌卡因组362例,布比卡因组377例.罗哌卡因与布比卡因比较,具有较短的感觉阻滞起效时间(Z=2.24,P=0.02,I2=20.5％,P＞0.05),与运动阻滞恢复时间(Z=5.70,P＜0.01,I2=58.9％,P＞0.05),但两者低血压发生率差别无统计学意义(Z=1.06,P＞0.05,I22=0,P＞0.05).结论 罗哌卡因麻醉效果确切,运动阻滞恢复快,具有较高的硬膜外阻滞麻醉优越性.     

Comparison of continuous epidural infusion of fentanyl and bupivacaine with intermittent epidural administration of morphine for postoperative pain management in children

Background: The aim of this study was to compare epidural infusion of bupivacaine and fentanyl and intermittent epidural morphine with regard to analgesic effect, and incidence and severity of side effects in children undergoing major abdominal or genito-urological surgery in order to improve the postoperative pain management of children. Methods: A double-blind, block-randomised study design was used. Thirty-one children aged 3 months to 6 years undergoing major abdominal or genito-urological surgery were studied. After induction of anaesthesia a lumbar epidural catheter was placed at L_3–4 or L_4–5. Postoperatively, the children received either 30 μg/kg of morphine every 8 h or a continuous infusion of fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml at a rate of 0.25 ml.kg^-1.h^-1. All children additionally received rectal paracetamol in doses of 50–100 mg.kg^-1. d^-1 on a regular basis, and if necessary supplementary intravenous morphine in doses of 50 μg/kg. Postoperatively, pain, administration of supplemental morphine and side effects were recorded 5 times by one observer during the day of surgery and the first postoperative day. All children had an epidural catheter throughout the study period. Results: Both regimens provided effective analgesia, but significantly better pain relief was obtained in children receiving the fentanyl/bupivacaine regimen. Sedation, pruritus, vomiting, and administration of antiemetics were seen in both treatment groups, and even though both the incidence and severity of side effects tended to be higher in children receiving morphine, no statistically significant difference was found. No episodes of respiratory depression or motor blockade were noticed. Conclusion: Continuous epidural infusion of fentanyl and bupivacaine was found to be superior to intermittent epidural morphine. The initial regimen should be fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml infused at a rate of 0.25 ml. kg^-1. h^-1.     

Variation in spread of analgesia and loss of temperature discrimination during intermittent postoperative epidural bupivacaine administration

The proximal-distal and bilateral extent of analgesia and loss of temperature discrimination were assessed during the initial 34.5 h after major abdominal surgery in ten patients receiving intermittent epidural bupivacaine injections according to a fixed dose regimen. Segmental spread of loss of temperature discrimination was invariably larger than analgesia at all times. During the later postoperative period (24-34 h) a pronounced intra-individual variation in both proximal-distal and bilateral spread of analgesia was observed despite identical epidural injections of bupivacaine. This variation in extent of analgesia was observed during injections of both 0.5% and 0.25% bupivacaine. The explanation of this observation is unknown but it may be shifts in catheter position, a variable disposition of the local anaesthetic agent or changes in the epidural space rather than tachyphylaxis.     

布比卡因、罗哌卡因与芬太尼不同配伍用于连续术后硬膜外镇痛安全性探讨

目的探讨布比卡因、罗哌卡因与芬太尼不同配伍用于连续术后硬膜外镇痛的效果、并发症及安全陛。方法1600例行连续术后硬膜外镇痛的患者,按所用镇痛药物配伍不同分为：0．1％布比卡因＋5μg／ml芬太尼组（B组,n=920）和0．2％罗哌卡因＋2μg／ml芬太尼组（R组,n=680）。对两组镇痛效果（视觉模拟评分及患者对镇痛效果的满意度）、并发症和处理措施进行总结分析。结果视觉模拟评分两组无差异（P〉0．05）。患者对镇痛的满意度R组明显高于B组（P〉0．05）。并发症的发生率B组高于R组（P〉0．05）。两组内年龄≥60岁的患者低血压的发生率高于年龄〈60岁者（P〈0．05）;女性患者恶心呕吐的发生率高于男性（P〈0．05）;腰段硬膜外镇痛患者下肢乏力或麻木的发生率明显高于胸段硬膜外镇痛患者（P〈0．05）。结论布比卡因、罗哌卡因与芬太尼不同配伍均可安全有效地用于连续术后硬膜外镇痛,罗哌卡因组并发症较少,并发症的发生与镇痛药物、年龄、性别及硬膜外置管部位有关。     

The effect of ulinastatin pre-treatment on vecuronium-induced neuromuscular block in patients with hepatic cirrhosis

The aim of this study was to investigate the effect of ulinastatin, a protease inhibitor, on the neuromuscular block produced by vecuronium in patients with hepatic cirrhosis. Thirty adult patients with hepatic cirrhosis were randomly allocated to receive ulinastatin (cirrhosis/ulinastatin group, n = 15) or saline (cirrhosis/saline group, n = 15). Fifteen healthy adult patients without hepatic cirrhosis comprised a control group. Patients were given a standardised anaesthetic that included nitrous oxide and isoflurane in oxygen, and fentanyl. A bolus dose of ulinastatin 5000 unit x kg(-1) was given to members of the cirrhosis/ulinastatin group. The same volume of normal saline was given to the other two groups. Two minutes later, vecuronium 0.1 mg x kg(-1) was given. The onset of neuromuscular block was significantly slower in the cirrhosis/ulinastatin group than in the cirrhosis/saline and control groups (p < 0.05). Spontaneous recovery of neuromuscular function was significantly quicker in the cirrhosis/ulinastatin and control groups than in the cirrhosis/saline group (p < 0.05). The time course of recovery in the cirrhosis/ulinastatin and control groups was similar. We conclude that in cirrhotic patients, ulinastatin delays the onset of neuromuscular block produced by vecuronium. After pretreatment with ulinastatin, the speed of recovery from neuromuscular block in patients with cirrhosis becomes similar to that seen in healthy patients.     

The effect of 0.5 % ropivacaine on epidural blood flow

Twenty patients scheduled for elective abdominal surgery received epidural analgesia with 20 ml 0.5% ropivacaine or 0.5% bupivacaine. Epidural blood flow was measured by an epidural 133Xe clearance technique on the day before surgery (no local anaesthetic) and again 1 h before surgery, 30 min after injection of the local anaesthetic during continuous infusion (8 ml/h). Median initial blood flow was 5.0 ml/min and 6.0 ml/min per 100 g tissue in patients receiving ropivacaine and bupivacaine, respectively. After epidural bupivacaine, blood flow increased in 8 of 10 patients to 6.9 ml/min per 100 g tissue (P less than 0.05) in contrast to a decrease in 9 of 10 patients to 3.3 ml/min per 100 g tissue after ropivacaine (P less than 0.05), (P less than 0.01 between groups). The median level of sensory analgesia was T3.5 and T4.5 in the ropivacaine and bupivacaine group, respectively (P greater than 0.05). The demonstrated vasoconstrictor effect of epidural ropivacaine may influence the duration of its local anaesthetic effect.     

The effect of peripheral hypothermia on a vecuronium-induced neuromuscular block

Seven healthy patients were investigated during midazolam-fentanyl nitrous oxide-oxygen anaesthesia. The mechanical twitch response of the adductor pollicis muscle was recorded simultaneously during bilateral supramaximal train-of-four (TOF) stimulation of the ulnar nerves at the wrist. Intense neuromuscular block was evaluated using the post-tetanic count (PTC) method. Core temperature and the peripheral skin temperature of one arm were kept normal and stable. Following cooling of the other arm to a peripheral hand skin temperature of 27 degrees C, vecuronium was administered in a bolus dose of 0.05 mg.kg-1 followed by maintenance doses of 0.02 mg.kg-1. In the hypothermic and the normothermic arm the onset time following the bolus dose was 180 +/- 40 (mean +/- s.d.) seconds and 140 +/- 30 s, respectively, the duration of action was 26.4 +/- 4.5 and 16.5 +/- 4.0 min and the recovery time was 265 +/- 90 and 130 +/- 60 s (P less than 0.01). The time course of action following maintenance doses showed a similar marked difference between the hypothermic and the normothermic arm. In the normothermic arm a close correlation was found between the number of post-tetanic twitches and the time to first response to TOF stimulation. In contrast, in the hypothermic arm the number of post-tetanic twitches showed great variation with a poor correlation to the duration of intense neuromuscular block. It is concluded that the time course of action of a vecuronium-induced neuromuscular block is markedly prolonged during peripheral hypothermia and intense neuromuscular block cannot reliably be assessed using the PTC method at low peripheral temperature.(ABSTRACT TRUNCATED AT 250 WORDS)     

罗哌卡因、左旋布比卡因与布比卡因低位硬膜外麻醉的比较

目的比较罗哌卡因、左旋布比卡因与布比卡因低位硬膜外麻醉的临床效果。方法60例行下腹部手术病人。随机分成三组,每组20例。Ⅰ组：0．5％罗哌卡因;Ⅱ组：0．5％左旋布比卡因;Ⅲ组：0．5％布比卡因。行连续低位硬膜外麻醉。观察感觉阻滞起效时间、感觉阻滞平面上界、运动阻滞起效时间、运动阻滞程度及麻醉质量。结果Ⅰ、Ⅱ和Ⅲ组首次局麻药用量分别为（14．38±1．57）、（14．75±0．50）和（13．80±1．30）ml。Ⅰ组运动阻滞起效时间比Ⅲ组长（P〈0．05）,Ⅰ组Bromage评分为1分的例数多于Ⅲ组（P〈0．05）。与Ⅲ组比较,Ⅰ、Ⅱ组感觉阻滞起效时间、感觉阻滞平面上界差异均无统计学意义。Ⅲ组SBP在感觉阻滞平面达上界及运动阻滞起效时有明显降低（P〈0．05）。结论0．5％罗哌旨因、左旋布比卡因或布比卡因连续硬膜外麻醉均可产生良好的感觉和运动阻滞,三种药物药效学相似。