Parasympathetic nervous activity after administration of atropine and neostigmine using heart rate spectral analysis

Recently, heart rate spectral analysis has become recognized as a powerful tool for quantitatively evaluating autonomic nervous system activity. The purpose of this study was to analyze parasympathetic nervous activity by heart rate spectral analysis after administration of atropine and neostigmine for reversal of residual neuromuscular blockade. For our study, 36 female patients (26–37 years of age), ASA physical status (PS) I, who were scheduled for laparoscopic examination, were randomly allocated to one of the following four groups: In group A (1∶1), 9 patients received 1.0mg atropine followed 4 min later by 1.0 mg neostigmine. In group B (1∶2), 9 patients received 0.5 mg atropine followed 4 min later by 1.0 mg neostigmine. In group C (1∶2.5), 9 patients received 1.0 mg atropine followed 4 min later by 2.5 mg neostigmine. In group D (1∶2 mix), 9 patients received a mixed solution of atropine 0.5 mg and neostigmine 1.0mg. After finishing the laparoscopic examination, additional anesthesia was maintained with 70% nitrous oxide, 30% oxygen, and 0.5% isoflurane. The control data were obtained 10 min after finishing the laparoscopic examination. After that, the data on atropine were obtained between 2 and 4min after administration of atropine, and the data on neostigmine were obtained between 5 and 7 min after administration of neostigmine. We selected power spectral density of the high-frequency component (HF-p) in heart rate spectral analysis as an index to assess parasympathetic activity. In groups A, B, and C, the HF-p decreased after administration of atropine. In groups B and C, the HF-p increased after administration of neostigmine as compared to the control. In group A, the HF-p increased after neostigmine but did not differ from the control. The difference between groups D and B was not statistically significant. From the results of this study, we concluded that the muscarinic effect of neostigmine could not be sufficiently blocked by atropine at 1/2 dosages of neostigmine, but could be sufficiently blocked by atropine at equivalent dosages of neostigmine, under light isoflurane anesthesia.     

新斯的明拮抗小儿和成年患者维库溴铵的残余肌松作用

目的 观察麻醉恢复期新斯的明拮抗小儿和成年全麻患者维库溴铵的残余肌松作用的剂量反应和安全性.方法 全麻下择期手术的小儿和成年患者各50例,维库溴铵首剂0.1 mg/kg,术中必要时追加0.05 mg/kg.采用加速度肌松监测仪监测四个成串反应的比值(train-of-four ratio,TOFR).当TOFR恢复至0.55时,小儿和成年患者分别随机分为5个亚组,分别给予新斯的明10、20、30、50 μg/kg及阿托品5、10、15、25μg/kg,对照组静脉注射生理盐水2 ml.观察TOFR恢复至0.7、0.9、1.0的时间及术后6、24 h恶心呕吐的发生情况.结果 新斯的明明显加快TOFR的恢复(P＜0.05),其中30μg/kg～50μg/kg效果均更明显(P＜0.05).小儿和成年患者新斯的明拮抗维库溴铵残余肌松作用的剂量反应曲线的差异无统计学意义(P＞0.05),拮抗5min时,小儿和成年患者新斯的明的ED95分别为(6.4±10.5)μg/kg和(2.7±19.2)μg/kg.术后6、24 h恶心呕吐情况的差异无统计学意义(P＞0.05).结论 在TOFR恢复至0.55时,小儿和成年患者新斯的明拮抗维库溴铵的残余肌松作用的效果无统计学差异,推荐使用小剂量的新斯的明进行拮抗,剂量不宜超过30μg/kg.     

Accelerated reversal of atracurium blockade with divided doses of neostigmine

The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of neuromuscular blockade was investigated. Neostigmine 0.05 mg X kg-1 was administered either in a single bolus dose (Group I, n = 16) or in an initial dose of 0.01 mg X kg-1 followed three minutes later by 0.04 mg X kg-1 (Group II, n = 16) for antagonism of atracurium-induced blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. The mean time (+/- SD) from the first injection of the drug until the train-of-four (TOF) ratio value had reached 0.75 was significantly shorter in Group II (p less than 0.05) than in Group I (391.8 +/- 83.3 and 468.6 +/- 150.3 seconds respectively). The rate of TOF ratio recovery was 2.5 times faster after neostigmine administration in divided doses. It is concluded that administration of neostigmine in divided doses, as described in this study, produced a significantly faster reversal of residual atracurium-induced neuromuscular blockade as compared to a single bolus administration.     

术后非去极化肌松药肌松残余拮抗新进展

背景非去极化肌松药在临床麻醉中使用非常普遍,术后不可避免地发生肌松残余作用,其危害主要为呼吸不良事件,严重可导致死亡。 目的有效合理的肌松拮抗能降低术后肌松残余的发生率,减少相关并发症,因此,拮抗至关重要。内容阐述非去极化肌松药使用后手术结束时是否需要拮抗、拮抗的时机、拮抗剂的剂量和新的拮抗模式。趋向选择性肌松拮抗可...     

Split-dose atropine versus glycopyrrolate with neostigmine for reversal of gallamine-induced neuromuscular blockade

The effects of a split-dose of atropine sulphate versus a single dose of glycopyrrolate given with neostigmine for the reversal of gallamine-induced neuromuscular blockade were studied in 55 patients undergoing gynaecological surgery. The patients were randomized to receive either a single dose of glycopyrrolate (7 micrograms.kg-1) or two doses of atropine (8 micrograms.kg-1 each), given with an interval of 1 min. There were no differences between the two methods with respect to percentage heart rate changes, salivation or arousal time. Four patients demonstrated cardiac arhythmias in the atropine group, whereas none occurred in the glycopyrrolate group (P less than 0.05). It is concluded that a split-dose of atropine has similar chronotropic effects to a single dose of glycopyrrolate for the reversal of gallamine-induced neuromuscular blockade. However, the finding of a higher incidence of cardiac arrhythmias in the atropine group suggests that this reversal regime should be reserved for patients without cardiac disease.     

The potencies of edrophonium and neostigmine as antagonists of pancuronium

Dose response curves were constructed for edrophonium and neostigmine when used to antagonise pancuronium, 0.07 mg/kg during thiopentone-nitrous oxide-halothane anaesthesia. The antagonist was given when 10% twitch height had been restored and the effect was measured 10 minutes later. Recoveries to 50% and 90% twitch height were achieved with 167 and 828 micrograms/kg of edrophonium, and 10.5 and 51 micrograms/kg of neostigmine. The dose response curves were parallel and neostigmine was 16 times more potent than edrophonium. Combinations of equipotent doses of edrophonium and neostigmine were also administered and produced additive but not synergistic effects. It is concluded that either edrophonium or neostigmine may be used for the reversal of pancuronium neuromuscular blockade, but the combination of the two offers no advantage.     

异氟醚对新斯的明拮抗维库溴铵肌松作用的影响

目的：研究一定浓度的异氟醚对新斯的明拮抗维库溴铵肌松作用的影响。方法：30例病人随机分为三组（各10例）：（1）丙泊酚静脉麻醉组,即对照组（P组）。（2）观察组。以异氟醚维持麻醉,再分为两组;术中呼气未异氟醚浓度均为1MAC,临近手术结束用新斯的明拮抗时,呼气末异氟醚浓度分别为1MAC（1M组（）和0．3MAC（0．3M组）,术中各组均连续输注维库溴铵,术毕以新斯的明0．035mg/kg拮抗并记录以下数据;维库溴铵输注速率,从拮抗开始到T1恢复到90％,TOF恢复到0．7和0．9的时间拮抗后15分钟时的T1,TOF比值,结果：1M组和0．3M组维库溴铵输注速率较P组降低IP＜0．05）,新斯的明拮抗后,0．3M组和1M组T1恢复到90％,TOF恢复到0．7和0．9的时间较P组延长（P＜0．05和P＜0．01）,1M组TOF恢复到0．9的时间较0＝3M组延长（P＜0．05）,在新斯的明拮抗后15分钟,0．3M组和1M组的T1和TOF比值均低于P组（P＜0．05）,1M组的TOF比值低于0．3M组（P＜0．05）,结论：呼气未浓度为1MAC和0．3MAC的异氟醚均能影响新斯的明对维库溴铵肌松作用的拮抗。     

Perioperative monitoring of neuromuscular transmission using acceleromyography prevents residual neuromuscular block following pancuronium

The frequency of postoperative residual neuromuscular block following the use of the long-acting non-depolarizing muscle relaxants is high, and manual evaluation of the response to nerve stimulation does not eliminate the problem. In this prospective and randomized study we evaluated the hypothesis that perioperative use of acceleromyography would allow for a more rational and precise administration of the long-acting muscle relaxant pancuronium resulting in a decrease in 1) the incidence and severity of postoperative residual neuromuscular block, 2) the amount of pancuronium used, and 3) the time from end of surgery to tracheal extubation. Forty adult patients were randomized into two groups, one managed without the use of a nerve stimulator, the other monitored using train-of-four (TOF) nerve stimulation and acceleromyography. All patients were anaesthetized with diazepam, fentanyl, thiopenione, nitrous oxide, and in some patients halothane, and they all received pancuronium 0.08–0.1 mg kg^-1 for tracheal intubation, and 1–2 mg for maintenance of neuromuscular block. Neostigmine 2.5 mg preceded by atropine 1 mg was administered for reversal. In the patients managed without a nerve stimulator, the trachea was extubated when the anaesthetist judged the neuromuscular function to have recovered adequately for upper airway protection and spontaneous ventilation. In patients monitored with acceleromyography, the trachea was extubaled when the TOF ratio was above 0.70. In all 40 patients, TOF ratio was measured using mechanomyography immediately after tracheal extubation and the patients were evaluated for clinical signs of residual neuromuscular block. Train-of-four ratios, as measured mechanically, varied between 0.26 and 0.96 (median 0.65) in the group not monitored dunng the operation with acceleromyography. Seven patients in this group were unable to sustain head lift for 5 seconds and five patients were unable to lift an arm to the opposite shoulder, as compared to 1 and 0 patients, respectively, in the group monitored using acceleromyography (P<0.05). The lime from end of surgery to tracheal extubation varied between 0 and 25 min (median 10 min) in the group not monitored as compared to 7–47 min (median 15 min) in the monitored group (P<0.01). There was no statistically significant difference in the total dose of pancuronium given in the two groups. It is concluded, that by using acceleromyography during Anaesthesia it is possible to avoid the problem of residual neuromuscular block following pancuronium. However, in this study this happened at the expense of a slightly prolonged recovery time (5 min longer). Under the conditions of the study the use of acceleromyography did not influence the amount of pancuronium used during anaesthesia.     

Accelerated onset of pancuronium with divided doses

To determine the consequences of administering neuromuscular relaxants in divided doses, pancuronium was given either in a single dose, 0.07 mg X kg-1, or in an initial dose of 0.007 mg X kg-1 followed three minutes later with 0.063 mg X kg-1. When the drug was administered in divided dosage the onset time was reduced, the block was more intense and its duration of action was prolonged. It is suggested that such changes may be advantageous in the provision of rapid intense paralysis.     

Recovery from pancuronium

The rate at which paralysis from pancuronium could be reversed by neostigmine was monitored in two groups of patients, one elderly and the other young adults. Some patients were found to have prolonged recovery times, and this slow reversal occurred more frequently in the older group of patients. Possible reasons for this are discussed.     

新斯的明拮抗国产阿曲库铵效果及对Q-T离散度的影响

目的研究不同剂量新斯的明拮抗国产阿曲库铵肌松恢复作用的效果及对QT离散度(QTd)的影响.方法30例ASA Ⅰ～Ⅱ级患者,随机分为三组,每组10例.分别给予新斯的明20μg/kg(N20组)、30μg/kg(N30组)和40μg/kg(N40组),观察拮抗阿曲库铵肌松作用恢复时间及对QTd的影响.结果新斯的明20μg/kg产生的肌松恢复效果弱于30μg/kg和40μg/kg,而30 μg/kg和40μg/kg所产生的效果相似.新斯的明20 μg/kg、30μ/kg对QTd的影响不明显,而40μg/kg新斯的明明显增大QTd.结论新斯的明剂量由20μg/kg增加到40 μg/kg,肌松恢复加快,但增大QTd.     

A randomised controlled trial comparing deep neuromuscular blockade reversed with sugammadex with moderate neuromuscular block reversed with neostigmine

Deep neuromuscular block aims to improve operative conditions during laparoscopic surgery with a lower intra-abdominal pressure. Studies are conflicting on whether meaningful improvements in quality of recovery occur beyond emergence, and whether lower intra-abdominal pressure is achieved. In this pragmatic randomised trial with 1:1 allocation, adults undergoing elective laparoscopic surgery were allocated to moderate neuromuscular block reversed with neostigmine, or deep neuromuscular block reversed with sugammadex. Allocation was revealed to the anaesthetist only. Primary outcome was cognitive recovery of the Postoperative Quality of Recovery Scale, 7 days after surgery. Secondary outcomes included recovery in other domains of the Postoperative Quality of Recovery Scale at 15 min and 40 min; days 1, 3, 7, 14; and 1 and 3 months after surgery. Chi-square test was used for the primary outcome, and generalised linear mixed model for recovery over time between groups. Of 350 participants randomised, 140 (deep) and 144 (moderate) were analysed for the primary outcome. There was no difference in the Postoperative Quality of Recovery Scale cognitive domain at day 7 (deep 92.9% vs. moderate 91.8%, OR 1.164; 95%CI 0.486–2.788, p = 0.826), or at any other time-point. No significant difference was observed for physiological, emotive, activities of daily living, nociception, or overall recovery. Length of stay in the recovery area (mean (SD) deep 108 (58) vs. moderate 109 (57) min, p = 0.78) and hospital (1.8 (1.9) vs. 2.6 (3.5) days, p = 0.019) was not different. Intra-abdominal pressure and surgical operating conditions were not different between groups. Deep neuromuscular block did not improve quality of recovery compared with moderate neuromuscular block in operative laparoscopic surgery over a 1-h duration.     

Comparison of reversal with neostigmine of low‐dose rocuronium vs. reversal with sugammadex of high‐dose rocuronium for a short procedure

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty‐four patients undergoing elective laryngeal micro‐surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg^?1 with neostigmine (50 μg.kg^?1 with glycopyrrolate 10 μg.kg^?1) reversal (moderate block group) vs. rocuronium 0.90 mg.kg^?1 with sugammadex (4 mg.kg^?1) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra‐operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro‐surgery, the use of rocuronium 0.9 mg.kg^?1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg^?1 with neostigmine.     

Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium

Three clinically used anticholinesterases--neostigmine, pyridostigmine, and edrophonium--were tested for their ability to reverse two levels (60% and 95%) of neuromuscular blockade produced by pancuronium. A controlled in vitro environment of the rat diaphragm-phrenic nerve system was used for the studies. Concentrations of anticholinesterases spanned the clinical range and were extended beyond to establish dose-response curves. Neostigmine was the most potent reversal drug (ED50 for 95% block 5.5 +/- 4 nM), followed by pyridostigmine (0.27 +/- 0.06 microM) and edrophonium (2.1 +/- 0.05 microM). The three drugs were equally effective at reversal of block and fade as measured by train-of-four stimulation. The dose-response curves for all three drugs showed a ceiling effect for reversal of tension and fade. Supraclinical concentrations of drug did not effect complete reversal, especially at 95% block. High concentrations of anticholinesterase led to randomly appearing hyperactivity manifested by spontaneous twitching and repetitive firing with severe fade on stimulation.     

Pretreatment with pancuronium before suxamethonium administration in patients heterozygous for the usual and the atypical plasma cholinesterase gene

The object of this study was to investigate whether pretreatment with pancuronium before i.v. injection of suxamethonium could cause prolonged neuromuscular blockade in patients heterozygous for the usual and the atypical plasma cholinesterase gene (E1uE1a). Forty-three patients, 23 with genotype E1uE1a and 20 with normal genotype (E1uE1u), were pretreated with pancuronium 0.01 mg.kg-1 followed by suxamethonium 1.5 mg.kg-1, and received either neurolept anaesthesia or halothane anaesthesia. Seven patients (E1uE1a) were given suxamethonium 1.5 mg.kg-1 without pretreatment. The duration and type of neuromuscular block were evaluated using train-of-four (TOF) nerve stimulation. Type of anaesthesia did not significantly influence the results. The duration of block following pretreatment was significantly longer in heterozygous patients than in normal patients. Time to 90% twitch height recovery was 10.7 +/- 1.2 min (mean +/- s.d.) in genotypically normal patients, and 18.0 +/- 4.2 min in patients with genotype E1uE1a. Pretreatment with pancuronium caused a significantly slower recovery of the TOF ratio (phase II block). Thus, a TOF ratio of 0.7 was always reached within 13 min in genotypically normal patients. In genotypically abnormal patients, the same TOF ratio was reached within 20 min in all but three patients. In these three patients time to 90% twitch height recovery was prolonged (18-31 min), and TOF ratio did not return to normal, but stabilized at about 0.35, 0.50, and 0.65, respectively. Injection of edrophonium restored normal neuromuscular function in 10 min. It is concluded that in patients heterozygous for the usual and the atypical gene, pretreatment with pancuronium in combination with an increased dose of suxamethonium may cause a phase II block and thus a prolonged neuromuscular block.     

Dose-response to pancuronium in identical twins

The dose-response to pancuronium was determined in identical twins within an hour with the same anesthetic technique. The dose-response curves did not differ from parallelism, but one infant was more sensitive to pancuronium than the other. The recovery rates were also different. The variation in the dose response to pancuronium seems to extend to identical twins.     

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.     

Interaction of verapamil with gallamine and pancuronium and reversal of combined neuromuscular blockade with neostigmine and edrophonium

In this in vitro study, the effects and interactions of verapamil with gallamine and pancuronium and reversal by edrophonium and neostigmine of combined neuromuscular blockade, produced by the muscle relaxants and verapamil, were studied in an avian skeletal muscle. The results show that verapamil reduced the amplitude of indirectly-elicited twitch tension and potentiated the neuromuscular blockade produce by the two muscle relaxants. Edrophonium and neostigmine reversed the neuromuscular blockade produce by the muscle relaxants alone, and in combination with verapamil. Edrophonium was more potent than neostigmine in reversing the combined neuromuscular blockade produced by the muscle relaxants with and without verapamil.     

Synergism between mivacurium and pancuronium in adults

Mivacurium could be a useful agent as a final dose of a muscle relaxant following pancuronium if only additivily exists between these agents. We examined the interaction between mivacurium and pancuronium in 70 patients (ASA I-II) during propofol-alfentanil-N₂O-C₂ anaesthesia. Neuromuscular function was monitored by adductor pollicis EMG.
Firstly we established dose-response curves for mivacurium and pancuronium. Thereafter, 20 patients received a combination of 0.5 times the ED₅₀ doses of mivacurium and pancuronium (cMP) determined in the first part of this study. Patients were randomized to receive the cMP to the same IV-line (n=10) or to two separate IV-lines in opposite hands (n=10).
ED₅₀ values for mivacurium and pancuronium were 57.7 and 37.1 μg kg^-1, respectively. Maximal neuromuscular block following the cMP was 91.8 ±5.0% (mean±SD). This was highly significantly different from the estimated 50% NMB if only additivity exists between mivacurium and pancuronium ( P =0.0001). After the cMP, the 25 75% recovery rime was 9.4± 1.3 min and the time to train-of-four ratio of 0.70 was 35.8±5.4 min. There was no statistical difference in any recorded neuromuscular parameter between the two subgroups receiving mivacurium and pancuronium to the same or to opposite hands ( P >040).
We conclude that a significant synergism exists between mivacurium and pancuronium which may indicate that mivacurium does not produce a short-acting NMB if given after pancuronium. We do not recommend using mivacurium together with pancuronium.     

Haemodynamic effects of high-dose vecuronium compared with pancuronium in beta-blocked patients with coronary artery disease during fentanyl-diazepam-nitrous oxide anaesthesia

Background. Different combinations of neuromuscular blockers and opioids have been used in patients with angina pectoris to provide cardiovascular stability and reduce risk of myocardial ischaemia during anaesthesia.
Methods. We have compared the haemodynamic effects of high-dose vecuronium (0.3 mg kg^-1) with those of a standard dose of pancuronium (0.1 mg kg^-1) in patients scheduled for coronary artery bypass grafting during fentanyl-diazepam-nitrous oxide anaesthesia. All patients were receiving beta-adrenergic blocking agents. The given doses of vecuronium and pancuronium are equieffective with respect to duration of neuromuscular blockade.
Results. During a 25-min experimental period following the administration of the randomly selected drug, no significant changes in the haemodynamic parameters were observed in the vecuronium group. The administration of pancuronium, however, resulted in a significant mean increase in heart rate (20%), rate-pressure product (23%) and cardiac index (21%). Following endotracheal intubation in the pancuronium group, we observed an additional significant increase in mean arterial pressure and rate-pressure product.
Conclusion. High-dose administration of vecuronium has minimal haemodynamic effects and may thus offer a better alternative than pancuronium for long-lasting neuromuscular blockade in patients with coronary artery disease during fentanyl-diazepam-nitrous oxide anaesthesia.