Rocuronium-induced Neuromuscular Block Is Affected by Chronic Carbamazepine Therapy

Background: Patients on chronic anticonvulsant drugs are relatively resistant to certain nondepolarizing neuromuscular blockers such as pancuronium, vecuronium, pipecuronium, doxacurium, or metocurine, but not resistant to mivacurium and atracurium. This study investigated the influence of chronic carbamazepine therapy on the neuromuscular block induced by the new muscle relaxant rocuronium.

Methods: Twenty-two otherwise healthy individuals scheduled for neurosurgical operations were studied: 11 of them were on chronic treatment with carbamazepine; the others served as control subjects. The median duration of carbamazepine therapy was 9 weeks (range, 4-312 weeks). After premedication with oral diazepam, anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide/oxygen and 0.5% inspired isoflurane. Rocuronium, 0.6 mg/kg (2 x ED95), was given for intubation. The ulnar nerve was stimulated, and the evoked electromyogram recorded using a Datex NMT monitor.

Results: Based on the response to the first of four stimuli, neither the lag time nor the onset-time differed between the two groups. However, the intervals of recovery to 10%, 25%, 50%, and 75% of the baseline response and the recovery index (RI, 25%-75%) were significantly shorter in patients on chronic carbamazepine therapy.     

Reversal of Rocuronium-induced Neuromuscular Block by the Selective Relaxant Binding Agent Sugammadex: A Dose-finding and Safety Study

Background: Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.

Methods: Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9.

Results: Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient.     

Reversal of Rocuronium-induced (1.2 mg/kg) Profound Neuromuscular Block by Sugammadex: A Multicenter, Dose-finding and Safety Study

Background: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified [gamma]-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients.

Methods: Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period.

Results: A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae.     

Onset and Duration of Rocuronium-induced Neuromuscular Blockade in Patients with Duchenne Muscular Dystrophy

Background: In patients with Duchenne muscular dystrophy (DMD) the response to nondepolarizing muscle relaxants is scarcely documented and conflicting. The current study was conducted to determine the time to peak effect and the time for complete spontaneous recovery after a single dose of 0.6 mg/kg of rocuronium in patients with DMD.

Methods: Twenty-four patients (12 with DMD, 12 controls, aged 10-16 yr) were studied. All patients were anesthetized with propofol and fentanyl/remifentanil. Neuromuscular transmission was monitored by acceleromyography. After induction all patients received a single dose of 0.6 mg/kg of rocuronium. The complete time course of onset and spontaneous recovery were recorded

Results: Significant (P < 0.01) increase in the onset times to 95% neuromuscular block was observed in DMD patients (median, 203 s; range, 90-420 s) compared with controls (median, 90 s; range, 60-195 s). The time between rocuronium administration and recovery of first twitch of the train-of-four to 90% was significantly (P < 0.01) prolonged in DMD compared with controls (median, 132 min; range, 61-209 min versus 39 min; 22-55 min). The recovery index was also significantly prolonged in the DMD group compared with controls (median, 28 min, range, 15-70 min versus 8 min; 3-14 min).     

琥珀胆碱对罗库溴铵肌松作用的影响

目的：本试验应用ＰＩ控制器自动化反馈控制罗库溴铵的输注,将肌松维持在恒定水平,通过确定罗库溴铵的稳态输注速率,来研究琥珀胆碱对罗库溴铵肌松作用的影响。方法：选择１４例ＡＳＡ分级Ⅰ～Ⅱ级的手术病人,随机分成对照组（７例）和试验组（７例）。对照组在麻醉诱导后,静注０．６ｍｇ／ｋｇ罗库溴铵进行气管插管;试验组则静注１．５ｍｇ／ｋｇ琥珀胆碱后气管插管,待肌松作用完全恢复后,再静注０．６ｍｇ／ｋｇ罗库溴铵,     

美维库铵持续静滴与单次静注肌松效应及恢复过程的临床药效学观察

目的 :观察美维库铵持续静滴和单次静注肌松效应及术后恢复的临床药效学指标。方法 :6 0例ASA分级Ⅰ～Ⅱ级复合全麻患者随机分为四组 ,每组 15例。美维库铵 0 2 5mg/kg给药后行气管插管 ,Ⅰ、Ⅱ组以微量泵持续静滴美维库铵 ,Ⅲ、Ⅳ组单次静注美维库铵维持肌松。术后Ⅰ、Ⅲ组患者待肌松自主恢复 ,Ⅱ、Ⅳ组静注新斯的明5 0 μg/kg、阿托品 10 μg/kg拮抗。结果 :实验提示 0 2 5mg/kg的美维库铵剂量可于 2 4± 0 6分钟内产生满意的插管条件 ,优秀率 95 %以上。Ⅰ、Ⅱ、Ⅲ、Ⅳ组平均用药量分别为 4 7± 1 2、5 0± 1 9、5 2± 2 2和 4 9± 1 8μg·kg-1·min-1,持续静滴组与单次静注组用药量无显著性差异 (P >0 0 5 )。Ⅰ、Ⅲ组恢复指数分别为 8 1± 2 3分钟和 8 7± 2 2分钟 (P >0 0 5 )。Ⅱ、Ⅳ组的恢复指数亦无明显差异 ,但比自然恢复组约缩短 2分钟左右。结论 :美维库铵持续静滴与单次静注用药量无明显差异 ,持续静滴可获得较好的肌松效果。术后使用新斯的明拮抗虽可加快肌缩力的恢复 ,但因其短效作用 ,故术后无需常规拮抗。     

乌司他丁对阿曲库铵神经肌肉阻滞效应的影响

目的观察乌司他丁对阿曲库铵神经肌肉阻滞效应的影响。方法选择择期胆道探查手术病人30例,随机分成两组乌司他丁组,麻醉诱导按顺序静脉注射咪唑安定1mg/kg、丙泊酚1mg/kg、芬太尼5μg/kg,然后给予乌司他丁5000U/kg,2min后给予阿曲库铵0.6mg/kg;对照组,麻醉诱导后,给予同等剂量生理盐水,2min后给予阿曲库铵0.6mg/kg。观测两组患者拇内收肌群TOF,记录T1消失所需时间及第1次TOF恢复时T1出现的时间。结果乌司他丁组阿曲库铵起效时间为(289.0±19.7)s,比对照组(226.4±11.2)s明显延长,恢复时间为(14.4±0.8)min,比对照组(19.8±1.7)min明显缩短(P<0.05)。结论乌司他丁可影响阿曲库胺对胆道探查手术全麻病人的神经肌肉阻滞效应。     

Early Reversal of Profound Rocuronium-induced Neuromuscular Blockade by Sugammadex in a Randomized Multicenter Study: Efficacy, Safety, and Pharmacokinetics

Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated.

Methods: Ninety-eight male adult patients were randomly assigned to receive sugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 min after 0.6 mg/kg rocuronium. Patients were anesthetized with propofol and fentanyl. The primary endpoint of the study was the time to achieve a recovery of train-of-four ratio to 0.9. Neuromuscular blockade was measured using acceleromyography. Concentrations of rocuronium and sugammadex were determined in venous blood and urine samples. A population pharmacokinetic model using NONMEM (GloboMax LLC, Hanover, MD) was applied.

Results: The mean time to recovery of the train-of-four ratio to 0.9 after dosing at 3, 5, and 15 min decreased from 52.1, 51.7, and 35.6 min, respectively, after administration of placebo to 1.8, 1.5, and 1.4 min, respectively, after 8 mg/kg sugammadex. Sugammadex was safe and well tolerated. However, 20.4% of patients showed signs of inadequate anesthesia after its administration. The median cumulative excretion of rocuronium in the urine over 24 h was 26% in the placebo group and increased to 58-74% after 4-8 mg/kg sugammadex. The mean plasma clearances of sugammadex and rocuronium were 0.084 and 0.26 l/min, respectively.     

Effect of Renal Failure and Cirrhosis on the Pharmacokinetics and Neuromuscular Effects of Rapacuronium Administered by Bolus Followed by Infusion

Background: Recent trials indicate that rapacuronium's pharmacokinetic characteristics are influenced by both renal failure and cirrhosis but the time course of a single bolus dose of 1.5 mg/kg is affected minimally. The authors reassessed these pharmacokinetic findings and examined the time course of the same bolus dose followed by a 30-min infusion.

Methods: During nitrous oxide-isoflurane anesthesia, patients with normal renal and hepatic function (n = 25), those with renal failure (n = 28), and those with cirrhosis (n = 6) received a bolus dose of rapacuronium (1.5 mg/kg) followed by a 30-min infusion adjusted to maintain 90-95% twitch depression. At 25% recovery, neostigmine was administered. Blood was sampled until 8 h after the infusion to determine concentrations of rapacuronium and its active metabolite ORG9488. Rapacuronium's pharmacokinetic parameters were determined using mixed-effects modeling.

Results: Onset and facilitated recovery of twitch depression were similar in the three groups. Patients with renal failure required 22% less rapacuronium to maintain target twitch depression during the infusion. Rapacuronium's plasma clearance was 24% smaller in renal failure and decreased 0.5%/yr of age; rapid distribution clearance was 51% smaller in men than in women. After the infusion, ORG9488 concentrations decreased markedly more slowly in patients with renal failure. Cirrhosis did not alter the pharmacokinetics of rapacuronium.     

Efficacy of Tactile-guided Reversal from Cisatracurium-induced Neuromuscular Block

Background: Because tactile evaluation is the most common form of clinical neuromuscular monitoring, this study examines the relative efficacy of antagonizing residual block at different levels of recovery of the tactile train-of-four (TOF) response.

Methods: Anesthesia was induced in 64 adults with 2-5 [mu]g/kg fentanyl and 1-3 mg/kg propofol and maintained with fentanyl, propofol, and nitrous oxide. The tactile response of the adductor pollicis to TOF stimulation was evaluated at one arm, and the mechanomyographic response was recorded at the other. Patients received 0.15 mg/kg cisatracurium and were randomized to receive 0.07 mg/kg neostigmine on reappearance of the first (group I), second (group II), third (group III), or fourth (group IV) tactile TOF response (16 patients per group). Times from administration of neostigmine until the TOF ratio recovered to 0.7 (R0.7), 0.8 (R0.8), and 0.9 (R0.9) were measured.

Results: Data are presented as median with range in parentheses. R0.7 was 10.3 (5.9-23.4), 7.6 (3.2-14.1), 5.0 (2.0-18.4), and 4.1 (2.4-11.0) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.8 was 16.6 (8.9-30.7), 9.8 (5.3-25.0), 8.3 (3.8-27.1), and 7.5 (3.0-74.5) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.9 was 22.2 (13.9-44.0), 20.2 (6.5-70.5), 17.1 (8.3-46.2), and 16.5 (6.5-143.3) min in groups I, II, III, and IV, respectively (no intergroup differences). Ten minutes after neostigmine, a TOF ratio of 0.7 or greater was achieved in 50, 75, 88, and 93% of patients in groups I, II, III, and IV, respectively (P < 0.05 group I > II, III, and IV). At 30 min, a TOF ratio of 0.9 or less was observed in 21, 13, 13, and 7% of patients in groups I, II, III, and IV respectively (no intergroup differences).     

七氟醚对心脏病病人维库溴铵肌松效力的影响

目的 :观察吸入七氟醚对维库溴铵肌松效力的影响。方法 :4 0例择期体外循环心内直视术病人随机分成两组 ,分别为静脉麻醉组 (对照组 )和静脉麻醉复合吸入 1 3MAC七氟醚组 (七氟醚组 ) ,采用累积剂量反应的方法测定两组维库溴铵的量效关系曲线。结果 :诱导期吸入七氟醚 15分钟后使维库溴铵的量效关系曲线左移 ,七氟醚组的ED50 和ED95分别为 19 2± 5 6和 3 7 0± 10 3 μg/kg ,与对照组的 3 0 7± 8 6和 5 7 8± 11 6μg/kg相比 ,分别减少3 6 5 %和 3 5 8% (P <0 0 1)。结论 :七氟醚麻醉能明显增强维库溴铵的肌松效力。     

Genotyping the Butyrylcholinesterase in Patients with Prolonged Neuromuscular Block after Succinylcholine

Background: Succinylcholine remains the standard neuromuscular blocking drug for tracheal intubation in emergency situations. The short duration of action is due to its rapid hydrolytic degradation by butyrylcholinesterase (plasmacholinesterase). Multiple variants of this enzyme are known (A, F, S, H, J, K variants) with different effects on enzyme activity. This study was undertaken to evaluate the use of molecular genetic methods in patients with clinically prolonged neuromuscular block.

Methods: Nine patients with a neuromuscular block of 14 min to 5 h were selected. All four exons of the butyrylcholinesterase were amplified by polymerase chain reaction and analyzed by automated sequencing. Molecular genetic results were compared with clinical relaxation time and with biochemical test results (total butyrylcholinesterase activity, dibucaine and fluoride inhibition).

Results: Seven of nine patients were mutation carriers. Five of these had more than one mutation. The A and K variants were the most frequent variations. Three of four patients who were homozygous for the A variant were also carriers of the K allele. The authors identified one novel mutation (G1294T) introducing a stop codon at amino acid position 432. The duration of neuromuscular block was substantially different between patients with identical butyrylcholinesterase genotypes.     

Comparison of Physostigmine and Neostigmine for Antagonism of Neuromuscular Block

The ability of physostigmine alone and in combination with neostigmine to reverse d-tubocurarine-induced neuromuscular block was evaluated in surgical patients. The relaxation was maintained at a level of90 % twitch suppression during balanced anaesthesia, and antagonism was attempted with physostigmine 1.5 mgX3; neostigmine 0.5 mgX3; neostigmine 1.0 mgX3; or with a combination of physostigmine 0.75 mg and neostigmine 0.5 mg × 3.
The measured parameters included the twitch force or EMG amplitude of the adductor pollicis brevis muscle after supramaximal 0.1 Hz stimulation and fading of these responses after repetitive 2 and 50 Hz stimuli. Although the restitution rate of twitch height and EMG amplitude were essentially the same with both antagonists, there was a considerable time-lag in regeneration of the fades after repetitive stimuli with physostigmine as compared with the neostigmine group. The addition of physostigmine to a subeffective dose of neostigmine resulted in antagonism comparable to that seen in other groups. The clinical antagonism was satisfactory in all patients receiving physostigmine. The divergence of relaxation-indicating parameters (twitch responses and fades) after physostigmine suggests dissimilar modes of action of the two antagonists at the neuromuscular junction.     

The Maximum Depth of an Atracurium Neuromuscular Block Antagonized by Edrophonium to Effect Adequate Recovery

Background: The inability of edrophonium to rapidly reverse a deep nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling effect to antagonism of neuromuscular block by edrophonium. A ceiling effect means that only a certain level of neuromuscular block could be antagonized by edrophonium. Neuromuscular block greater than this could not be completely antagonized irrespective of the dose of edrophonium administered. The purpose of this study was to determine whether a ceiling effect occurred for antagonism of an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum level of block that could be antagonized by edrophonium.

Methods: In 30 adult patients, atracurium was administered to maintain a constant neuromuscular block. The level of block varied between patients. Evoked adductor pollicis twitch tension was monitored. Incremental doses of edrophonium were administered while the infusion of atracurium continued. Increments were given until adequate recovery occurred, as defined by a train-of-four (TOF) ratio greater or equal to 70%, or until no further antagonism of the block could be achieved. The probability of being able to effect adequate recovery by antagonism with edrophonium was determined using a logistic regression model. Cumulative dose-response curves were constructed using the logit transformation of the neuromuscular effect versus the logarithm of the cumulative dose of edrophonium.

Results: In 14 patients with a block of 25-77% depression of the first twitch response, antagonism by edrophonium to a TOF ratio greater or equal to 70% was possible, whereas in 16 patients with a 60-92% depression of T1, a TOF ratio > 70% was not achievable, indicating that a ceiling effect for antagonism by edrophonium occurred. A block of 67 plus/minus 3% (mean plus/minus SE) had a 50% probability of adequate antagonism. In patients in whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic effect occurred with an edrophonium dose of 0.8 plus/minus 0.33 mg *symbol* kg sup -1 (mean plus/minus SD).     

Mivacurium Neuromuscular Block at the Adductor Muscles of the Larynx and Adductor Pollicis in Humans

Background: Laryngeal muscles must be paralyzed for tracheal intubation. Time to peak effect (onset time) is shorter and intensity of blockade is less at laryngeal muscles compared with the adductor pollicis. The authors' aim in this study was to determine the neuromuscular effects of mivacurium at the laryngeal adductor muscles and the adductor pollicis.

Methods: In 22 adults, anesthesia was induced and maintained with propofol and alfentanil. The force of contraction of the adductor pollicis was recorded, and the laryngeal response was evaluated by measuring the pressure change in the cuff of a tracheal tube positioned between the vocal cords after train-of-four stimulation. Mivacurium (0.07 mg *symbol* kg sup -1 or 0.14 mg *symbol* kg sup -1) was given intravenously (10 s).

Results: With 0.07 mg *symbol* kg sup -1 mivacurium, onset time was 151+/-40 s (mean+/-SD) at the larynx and 241+/- 79 s at the adductor pollicis, respectively (P < 0.005). Maximum block was 78+/-18% and 95+/-8%, respectively (P < 0.002), and time to 90% recovery was 11.1+/-2.9 min and 23.3+/-7.6 min, respectively (P < 0.001). With 0.14 mg *symbol* kg sup -1 mivacurium, onset time also was more rapid at the vocal cords (137+/-20 s) than at the adductor pollicis (201+/-59 s, P < 0.01). Maximum block was 90+/-7% and 99+/-1% (P < 0.005), and time to 90% recovery was 16.4+/-4.9 min and 27.4+/-7.8 min, respectively (P < 0.01).     

低温对肌肉松弛药作用消退的影响

目的与方法：使用孤立前臂技术、前臂局部降温、记录单个重复刺激尺神经时姆指内收肌收缩反应。在志愿受试者双前臂上观察中度低温对维库溴铵、罗库溴铵（ｒｏｃｕｒｏｎｉｕｍ）和十季铵（ｄｅ－ｃａｍｅｔｈｏｎｉｕｍ）消退作用的影响。结果：当皮肤温度下降５～７℃时，维库溴铵和罗库溴铵的恢复指数从常温时８．８±１．５和９．６±２．７分别延长至１５．６±３．３和１９．６±６．５（Ｐ＜０．０１），十季铵的恢复指数无显著改变。恢复指数变化与温度变化间比例常数维库溴铵和罗库溴铵分别为３．２１±１．３４和２．８６±０．８２，十季铵为１．２９±０．２６。结论：非去极化肌松药维库溴铵和罗库溴铵作用的消除可能是受温度影响的生物学过程，去极化肌松药十季铵作用的消除可能是较少受温度变化影响的物理学过程。     

ORG 9487 Neuromuscular Block at the Adductor Pollicis and the Laryngeal Adductor Muscles in Humans

Background: ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis.

Methods: In 30 adults, anesthesia was induced with propofol (2-5 mg/kg) and fentanyl (2-3 micro gram/kg). After train-of-four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group).

Results: Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P < 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/- 14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/- 20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P <0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/- 7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min at the adductor pollicis muscle.     

Inhibition of the Enzymic Degradation of Suxamethonium and Mivacurium Increases the Onset Time of Submaximal Neuromuscular Block

Background: The factors that influence the onset time of submaximal (< 100%) neuromuscular block are not fully known. The authors hypothesized that differences in the rate of decrease in the plasma concentration result in differences in the rate of equilibration between plasma and biophase and thus in different onset times. If this hypothesis is valid, inhibition of the enzymic degradation of muscle relaxants should increase the onset time of neuromuscular block.

Methods: Twenty pigs received either suxamethonium or mivacurium. Dose finding (70% block) was done for each pig. The enzymic degradation of the muscle relaxant was randomly inhibited by selective inhibition of plasma cholinesterase activity by tetraisopropyl pyrophosphoramide (10 pigs) or was not inhibited (10 pigs). Plasma cholinesterase activities and the mechanomyographic muscle response after peroneal nerve stimulation (0.1 Hz) were measured.

Results: Inhibition of plasma cholinesterase activity (by 93% and 89%, respectively) increased the onset time of suxamethonium from a median of 40 s (range, 20-45 s) to 131 s (range, 114-166 s; P = 0.009) and of mivacurium from a median of 52 s (range, 40-59 s) to 105 s (range, 90-125 s; P = 0.009). Inhibition of degradation decreased the effective dose of suxamethonium that resulted in 70% depression of the initial twitch height from 900 [micro sign]g/kg (range, 400-1,000 [micro sign]g/kg) to 150 [micro sign]g/kg (range, 135 - 150 [micro sign]g/kg) and of mivacurium from 100 [micro sign]g/kg (range, 80-150 [micro sign]g/kg) to 35 [micro sign]g/kg (range, 20-50 [micro sign]g/kg).