Nondepolarizing neuromuscular blocking drugs and train-of-four fade

The aim of this study was to examine differences in prejunctional effects of different relaxants by measuring the train-offour (TOF) fade during the onset and recovery of neuromuscular block. The relaxants studied were atracurium (225 μg · kg^?1), mivacurium (65 μg · kg^?1) rocuronium (300 μg · kg^?1)) and vecuronium (40 μg · kg^?1)). The TOF ratios were measured at approximate heights of T₁) (first response in the TOF) of 90, 75, 50, and 25%. The TOF fade (as shown by lower TOF ratios) increased with a decrease in the T₁) during onset of neuromuscular block. Although there was a slightly greater fade with atracurium and rocuronium during the onset of block, the differences among the relaxants were insignificant. It is concluded that the relative prejunctional effects of these relaxants are similar.     

Muskelrelaxanzien Neue Substanzen und neuromuskuläres Monitoring

Introduction: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards. Muscle relaxants: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED₉₅ of rocuronium provides good or excellent intubating conditions within 60 to 90?s. Slight vagolytic effects were reported following injection of 0.6?mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED₉₅ did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid breakdown by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.     

Beeinflussung der Pharmakodynamik von Rocuronium durch Cimetidin

Cimetidine is a commonly used H₂-receptor antagonist that has been recommended for the prevention of acid aspiration syndrome and has been shown to potentiate vecuronium-induced neuromuscular block. The present study was designed to investigate the influence of a single IV dose of cimetidine on the neuromuscular effects of rocuronium, an analogue of vecuronium with a short onset time. Methods. Twenty adults aged 18–65 years were included in the study with their informed consent and approval of the Ethics Committee. Following oxazepam premedication, 10 patients were randomly allocated to receive cimetidine 400 mg IV 30 min before anaesthesia. After fentanyl and thiopentone induction, single-twitch stimulation of the ulnar nerve was performed every 10 s. Following stabilisation of control responses, patients received rocuronium 0.6 mg/kg for intubation. Anaesthesia was maintained with enflurane ≤0.8 vol.% (end-tidal) and 65% nitrous oxide. Onset time and recovery times to 25% and 75% of the twitch control values were recorded. Results. Onset and recovery times did not differ between groups. Conclusions. The results of the present study demonstrate that cimetidine does not increase the duration of rocuronium neuromuscular blockade. Inhibition of the cytochrome P450 system or a direct effect at the neuromuscular junction have been suggested as the mechanisms of drug interaction associated with cimetidine. Impairment of hepatic microsomal drug metabolism results in a prolonged duration of action of vecuronium, which appears to be eliminated primarily via the liver. Data on the elimination pathway of rocuronium in humans are not available. The fact that cimetidine does not alter the recovery from rocuronium-induced neuromuscular block confirms a previous suggestion that rocuronium may not be eliminated principally by the liver. A direct effect of cimetidine on the neuromuscular junction could not be confirmed by this study. Therefore, cimetidine can be given as premedication without a risk of prolonged rocuronium block.     

Effects of vecuronium and rocuronium in antagonistic laryngeal muscles and the anterior tibial muscle in the cat

BACKGROUND: Adequate vocal cord paralysis and full recovery of laryngeal muscle function are important when muscle relaxants are used perioperatively. This study was designed to compare the effects of vecuronium and rocuronium at the vocal cord abductor and adductor muscles and the anterior tibial muscle in cats. METHODS: Twelve adult cats were studied under pentobarbitone-N2O/O2-anesthesia. After supramaximal electrical stimulation of the peroneal nerve and the recurrent laryngeal nerve (0.1 Hz and intermittent train-of-four) evoked electromyographic responses were obtained from the anterior tibial muscle, the posterior cricoarytenoid muscle (vocal cord abductor) and two vocal cord adductor muscles, the lateral cricoarytenoid and the vocal muscle. Six cats received bolus doses of increasing size of vecuronium (ED90 22.5 microg x kg(-1)) and six cats rocuronium (ED90 90 microg x kg(-1)). RESULTS: Equipotent doses of vecuronium and rocuronium caused a similar degree of paralysis in all muscles (vecuronium ED90: 70% blockade at the posterior cricoarytenoid, 83% at the lateral cricoarytenoid, 84% at the vocal muscle and 90% at the anterior tibial muscle; rocuronium ED90: 71% at the posterior cricoarytenoid, 67% at the lateral cricoarytenoid, 78% at the vocal muscle and 90% at the anterior tibial muscle; vecuronium 2 x ED90: 93% blockade at the posterior cricoarytenoid, 95% at the lateral cricoarytenoid, 97% at the vocal muscle and 99% at the anterior tibial muscle; rocuronium 2 x ED90: 89% blockade at the posterior and lateral cricoarytenoid, 93% at the vocal muscle and 100% at the anterior tibial muscle). Onset time was significantly shorter at the posterior cricoarytenoid muscle (290 s) compared to the lateral cricoarytenoid muscle (400 s) after vecuronium ED90 and to the vocal muscle (150 s versus 210 s) after rocuronium ED90. Compared to the anterior tibial muscle (interval 25-75%: 6.5 min after vecuronium 2 x ED90 and 3.3 min after rocuronium 2 x ED90 and to the posterior cricoarytenoid muscle (interval 25-75%: 7 min after vecuronium 2 x ED90 and 4.3 min after rocuronium 2 x ED90), recovery of laryngeal adductor muscle function was markedly delayed with both neuromuscular blocking drugs (interval 25-75% at the lateral cricoarytenoid and vocal muscle: 14 min and 15.8 min after vecuronium 2 x ED90 and 10.3 min and 11.6 min after rocuronium 2 x ED90 respectively). CONCLUSION: In cats, the time course of neuromuscular blockade after vecuronium and rocuronium differs in antagonistic laryngeal muscles. The protective laryngeal function of glottis closure recovers later than vocal cord abduction after both vecuronium and rocuronium.     

A comparison between vecuronium and atracurium in myasthenia gravis

We evaluated the effect of vecuronium bromide and atracurium besylate on the train–of–four response in the management of muscle relaxation in 20 patients with myasthenia gravis (MG) who were undergoing thymectomy. We confirmed the safe use of these two non–depolarizing muscle relaxants in MG patients. Vecuronium (0.04 mg–kg^-1) demonstrated a lesser clinical duration than did atracurium (0.2 mg–kg^-1) (38± 19 vs 50 ± 21 min, mean ± s.e.mean). The recovery time for vecuronium patients was shorter than that for atracurium patients (22 ± 18 vs 38± 18 min), but the time until onset of neuromuscular blockade was longer with vecuronium (246 ±105 vs 107 ± 103 s). During spontaneous recovery from neuromuscular relaxation, at Tl/C of 25% and 100%, the train–of–four fade with vecuronium was significantly greater than that with atracurium (0.04 ± 0.02, 0.16 ± 0.03 vs 0.17 ±0.01, 0.83 ± 0.03), suggesting that vecuronium had a greater prejunctional effect than did atracurium.     

Die Wechselwirkung von Rocuronium und Rauchen Der Einfluß des Rauchens auf die neuromuskuläre Übertragung nach Rocuronium

Recent studies have shown different results concerning the effects of smoking on neuromuscular blocking agents. Some reports indicate that smokers need higher doses of vecuronium, but are more sensitive to atracurium. The aim of this study was to evaluate the effects of smoking on onset and recovery time after a single 0.6 mg/kg intubating dose of rocuronium an analog of vecuronium. Methods: Following institutional approval and informed consent, 20 smokers (>10 cigarettes/day) and 20 nonsmokers were included in the study. Following oxazepam premedication and induction with fentanyl and thiopental, single-twitch stimulation of the ulnar nerve was performed every 10 s. Following stabilisation of control responses, patients received rocuronium 0.6 mg/kg for intubation. Anaesthesia was maintained with enflurane ≤0.8 vol.% (end-tidal) and 65% nitrous oxide in oxygen. Onset time and recovery to 25% and 75% of the twitch control values were recorded. Results: Onset and recovery times were not different between smokers and nonsmokers. Conclusions: The results of the present study suggest that chronic nicotine exposure does not change onset time or duration of rocuronium neuromuscular blockade. A previous study found a greater need for vecuronium in smokers and discussed stimulation of the neuromuscular junction and enhanced biotransformation due to the enzyme-inducing properties of nicotine. The differences in our results could be partly due to a longer period of refraining from smoking in our patients, leading to very low nicotine blood concentrations without the proposed receptor-stimulating effect. Another cause for different behaviour of the two analogs could be different elimination pathways. Recent investigations suggest that rocuronium may not be eliminated principally by the liver. Therefore, enhanced nicotine-induced biotransformation, as suggested for vecuronium, would not occur with rocuronium.     

七氟烷对罗库溴铵、维库溴铵及阿曲库铵临床药效的影响

目的 以丙泊酚为对照,观察1.3 MAC的七氟烷对罗库溴铵、维库溴铵及阿曲库铵临床药效的影响.方法 选择60例择期腹部手术的病人随机分为6组,每组10人.七氟烷罗库溴铵组(sR组)、七氟烷维库溴铵组(SV组)及七氟烷阿曲库铵组(SA组)分别吸入1.3 MAC的七氟烷及静注芬太尼维持麻醉,丙泊酚罗库溴铵组(CR组)、丙泊酚维库溴铵组(CV组)及丙泊酚阿曲库铵组(CA组)以丙泊酚6 mg·kg-1·h-1～8 mg·kg～·h-1及芬太尼维持麻醉.监测起效时间、最大抑制程度、作用时间、维持速率、恢复时间、恢复指数.结果 七氟烷组与相应的对照组在最大抑制程度、恢复指数方面的无统计学差异,起效时间、作用时间、维持速率、恢复时间有统计学差异.结论 七氟烷能明显延长罗库溴铵、维库溴铵以及阿曲库铵的作用时间和恢复时间并减少其起效时间、维持剂量,但对最大抑制程度和恢复指数则无明显影响.     

Spontaneous recovery of residual neuromuscular blockade after atracurium or vecuronium during isoflurane anaesthesia

With atracurium and vecuronium, spontaneous recovery of residual neuromuscular blockade monitored electromyographically during 0.5% isoflurane anaesthesia was studied in 60 patients undergoing plastic surgery. After thiopentone, in random order, either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 was administered and isoflurane added to N2O and O2 mixture. Following spontaneous recovery of both the single twitch amplitude (T1) to 75% of the control value and the train-of-four ratio (TOF ratio) to 75%, incremental doses of the relaxant were given to maintain the T1 at less than 10%. Before the end of surgery, the blockade was again permitted to recover spontaneously. During the initial spontaneous recovery, the mean recovery time of T1 from 25% to 75% (the recovery index) with atracurium was longer (P less than 0.001) than that with vecuronium (13.2 min and 10.1 min, respectively) but, during the second recovery, the mean recovery index was shorter (P less than 0.05) with atracurium than with vecuronium (16.1 min and 19.8 min, respectively). The recovery time from T1 75% to TOF ratio 75%, indicating the recovery rate of residual neuromuscular blockade, with atracurium was about 15 min after both the initial and the second recoveries. With vecuronium, the respective recovery times were significantly (P less than 0.001) longer (25.6 min and 38.5 min, respectively). It is concluded that with vecuronium there is slower spontaneous recovery of residual neuromuscular blockade than with atracurium.     

Atracurium: neuromuscular blockade in repeated administration

The neuromuscular blocking action of repeated injections of atracurium and vecuronium was studied in 74 surgical patients during balanced anaesthesia (methohexitone or etomidate, intubation after suxamethonium, fentanyl, droperidol, N2O). The initial bolus dose (ID) of atracurium was 0.25 mg/kg and of vecuronium 0.05 mg/kg followed by repeated increments (RD) of atracurium 0.1 mg/kg and vecuronium 0.0125 mg/kg when neuromuscular function (EMG) had recovered to about 30% of pre-relaxant control. Dose-response relationships revealed atracurium to be about 1/5 as potent as vecuronium; the ED50 of atracurium was 0.13 +/- 0.03 mg/kg and of vecuronium 0.023 +/- 0.007 mg/kg. The ID of both relaxants produced a neuromuscular blockade of about 90% within 4 min. The duration from the time of injection to 30% recovery was slightly longer in atracurium 26 +/- 9 min. In all patients the RD produced within 3.5 min satisfactory muscle relaxation with a neuromuscular block of about 85%. The mean duration of atracurium (18 min) was 5-10 min longer than of vecuronium (12 min). To maintain good surgical relaxation (more than 70% blockade) atracurium 0.32 mg/kg X h and vecuronium 0.056 mg/kg X h were required. No cumulation could be measured after repeated injections. The recovery time of atracurium and vecuronium at the end of anaesthesia was 10-12 min. Neither cardiovascular side-effects nor signs of histamine release were observed after both relaxants in our particular dose range. It is concluded, that atracurium is a favourable blocker for anaesthetic practice: The time of onset is approximately the same compared with vecuronium. The duration of action, however, is slightly longer but still truly intermediate long.(ABSTRACT TRUNCATED AT 250 WORDS)     

Train–of–four fade during onset of neuromuscular block with nondepolarising neuromuscular blocking agents

Fade in the train-of-four (TOF) responses during onset of neuromuscular block was studied following administration of atracurium (225 or 450 micrograms/kg), vecuronium (40 or 80 micrograms/kg), pancuronium (60 or 120 micrograms/kg) and tubocurarine (450 micrograms/kg). TOF ratios were measured at approximate heights of T1 (first response in the TOF) of 75, 50 and 25%. Fade in TOF increased as the height of T1 decreased, with maximum fade being observed at T1 of 25%. The greatest difference between relaxants was observed at T1 of 25%, vecuronium showing the least fade and pancuronium, atracurium and tubocurarine showing increasing fade, in that order. The difference between atracurium and tubocurarine or between vecuronium and pancuronium was not significant, but the degree of TOF fade was significantly greater with atracurium and tubocurarine in comparison to vecuronium or pancuronium.     

The effect of phenytoin on the magnitude and duration of neuromuscular block following atracurium or vecuronium

Patients chronically receiving anticonvulsants have been reported to be resistant to the long-acting competitive neuromuscular blockers. This study examines the effects of atracurium and vecuronium on 100 neurosurgical patients; 50 receiving chronic phenytoin therapy (group I) and 50 controls (group II). During O2/N2O/halothane anesthesia, five patients in each group were given a bolus of vecuronium 0.1 mg/kg, and a different five patients in each group were given atracurium 0.5 mg/kg, to produce neuromuscular blockade in excess of 95%. The time to maximum blockade and the recovery from atracurium was unaffected by phenytoin therapy. Recovery from vecuronium was enhanced in the phenytoin group, as demonstrated by the recovery index, defined as the time required for recovery from 25-75% of the control neuromuscular response (7.9 +/- 2.2 min compared with 17.8 +/- 5.1 min in controls, P less than 0.005). Similarly, the total duration of neuromuscular blockade, defined as recovery to 90% of control response, was significantly shorter in the phenytoin group (31.9 +/- 6.0 min compared with 69.7 +/- 12.9 min in controls, P less than 0.001). The remaining 40 patients from each group were given a preselected dose of either vecuronium (0.02-0.06 mg/kg) or atracurium (0.10-0.25 mg/kg) during anesthesia with O2/N2O/fentanyl, to generate dose-response curves for the relaxants. Using analysis of covariance, the slopes and elevations for atracurium were found to be essentially identical in the two groups; as were the calculated ED50 and ED95. Patients receiving chronic phenytoin therapy were resistant to vecuronium-induced neuromuscular blockade. With vecuronium, the dose-response curves for the two groups were parallel; the curve for phenytoin patients was shifted to the right.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the Neuromuscular Blocking Effect of Atracurium and Vecuronium on the Adductor Pollicis and the Geniohyoid Muscle in Humans

Background: Residual paralysis of suprahyoid muscles may occur when the adductor pollicis response has completely recovered after the administration of a neuromuscular blocking agent. The response of the geniohyoid muscle to intubating doses of muscle relaxants is evaluated and compared to that of adductor pollicis.

Methods: Sixteen patients undergoing elective surgery under general anesthesia were given 5-7 mg *symbol* kg sup -1 thiopental and 2 micro gram *symbol* kg sup -1 fentanyl intravenously for induction of anesthesia. Eight (half) patients then received 0.5 mg *symbol* kg sup -1 atracurium, and the other eight received 0.1 mg *symbol* kg sup -1 vecuronium. The evoked response (twitch height, TH) of the adductor pollicis was monitored by measuring the integrated electromyographic response (AP EMG) on one limb and the mechanical response, using a force transducer (AP force), on the other. The activity of geniohyoid muscle (GH EMG) was measured using submental percutaneous electrodes. The following variables were measured: maximal TH depression; onset time for neuromuscular blockade to 50%, 90%, and maximal TH depression (OT50, OT90, and OTmax); times between administration of neuromuscular blocking agent and TH recovery to 10%, 25%, 50%, 75%, and 90% of control; and time for return of train-of-four ratio to return to 0.7.

Results: The principal findings were (1) OTmax was significantly (P < 0.01) shorter for geniohyoid than for adductor pollicis after either atracurium or vecuronium (OTmax was 216, 256, and 175 s for AP force, AP EMG, and GH EMG, with atracurium and 181, 199, and 144 s with vecuronium, respectively), and (2) the evoked EMG of geniohyoid recovered at the same speed as the EMG of adductor pollicis after an intubating dose of atracurium or vecuronium (recovery of TH to 75% of control at 50, 48, 42 min with AP force, AP EMG, and GH EMG with atracurium and 46, 45, and 42 min with vecuronium, respectively).     

Postoperative residual block after intermediate-acting neuromuscular blocking drugs

The frequency and duration of postoperative residual neuromuscular block on arrival of 150 patients in the recovery ward following the use of vecuronium (n = 50), atracurium (n = 50) and rocuronium (n = 50) were recorded. Residual block was defined as a train-of-four ratio of <0.8. An additional group of 10 patients received no neuromuscular blocking drugs during anaesthesia. The incidence of postoperative residual neuromuscular block was 64%, 52% and 39% after the use of vecuronium, atracurium and rocuronium, respectively. Similar numbers of patients were not able to maintain a sustained head or leg lift for 5 s on arrival in the recovery ward. The mean [range] times to attaining a train-of-four ratio of > or =0.8 after arrival in the recovery ward were 9.2 [1-61], 6.9 [1-24] and 14.7 [1.5-83] min for vecuronium, atracurium and rocuronium, respectively. None of the 10 patients who did not receive neuromuscular blocking drugs had train-of-four ratios <0.8 on arrival in the recovery ward. It is concluded that a large proportion of patients arrive in the recovery ward with a train-of-four ratio <0.8, even with the use of intermediate-acting neuromuscular blocking drugs. Although the residual block is relatively short lasting, it may occasionally be prolonged, requiring close observation and monitoring of such patients in the recovery ward.     

Atracurium, cisatracurium, vecuronium and rocuronium in patients with renal failure

AIM: The cumulative index, the recovery, the onset and the duration of action, of atracurium, cisatracurium, vecuronium and rocuronium in uremic patients undergoing kidney transplantation compared to healthy patients undergoing general surgery were studied. METHODS: In all patients (64 uremic vs 62 "healthy" patients) after anesthesia induction, atracurium 0.5 mgxkg(-1) or cisatracurium 0.15 mgxkg(-1) or vecuronium 0.1 mgxkg(-1) or rocuronium 0.6 mgxkg(-1) were administered, and at the end of surgery when T1 reached 25% neostigmine 0.05 mgxkg(-1) was given. Neuro-muscu-lar transmission was monitored by accelerometry (TOF-GUARD, Organon). RESULTS: Cumulative index of vecuronium (1.3+/-0.1 vs 1.06+/-0.11, p<0.001) and rocuronium (1.45+/-0.18 vs 1.04+/-0.16, p<0.001), recovery index (time of T1 25-75) of atracurium (14.2+/-5 vs 9+/-4, p<0.005), cisatracurium (18.7+/-3 vs 9.1, p<0.001), vecuronium (18.5+/-3 vs 12.5+/-3, p<0.001) and rocuronium (18+/-6 vs 11+/-4, p<0.001) and interval T1 25% to TOF 0.8 of cisatracurium (20.5+/-1.2 vs 16+/-2.1, p<0.001) and vecuronium (27+/-6.3 vs 20+/-3.3, p<0.001) were longer in uremic patients. The onset time and the duration of action of atracurium, cisatracurium, vecuronium and rocuronium were similar in all groups compared to controls one. CONCLUSION: In patients with renal failure the use of atracurium, cisatracurium, vecuronium and rocuronium is suitable and predictable in terms of onset, and duration of action. Care has to be taken to vecuronium and rocuronium cumulative index. Neuromuscular trasmission has to be always monitored.     

The non-depolarizing myorelaxants in orotracheal intubation. A clinical comparison

The present study was designed to compare the rapidity of onset of neuromuscular blockade after administration of 5 different neuromuscular relaxants (succinylcholine, d-tubocurarine, pancuronium, atracurium and vecuronium) in 75 patients, randomly allocated in 5 treatment groups. The facilitation for endotracheal intubation was evaluated using a clinical score. The for onset relaxation was shorter when using succinylcholine. Among non-depolarizing relaxants an adequate facilitation for endotracheal intubation was observed, two minutes after administration of atracurium and vecuronium, while endotracheal intubation was difficult when using d-tubocuranine and pancuronium.     

Die klinische Pharmakologie neuer Benzylisochinolin-Diester-Verbindungen Unter besonderer Berücksichtigung von Cisatracurium und Mivacurium

The benzylisochinoline muscle relaxants have a highly selective affinity to the motor endplate which is associated with an absence of autonomic side effects such as ganglionic and vagus block. The requirement of only low clinical doses also reduces histamine liberation. Muscle relaxants with high neuromuscular blocking potency have a slow onset. Both atracurium and cisatracurium undergo Hofmann-Elimination in the plasma whereas mivacurium is hydrolyzed by pseudocholinesterase. The difference in kinetics between these pathways render atracurium and cisatracurium muscle relaxants of intermediate duration of action while mivacurium is short acting. Cisatracurium, one of the ten stereoisomeres of atracurium, is 3 to 4 times as potent as atracurium, does not release histamine, has no cardiovascular side effects and, due to the small clinical doses resulting from its high neuromuscular blocking potency, produces only negligible quantities of laudanosine. Its ED₉₅ is 0.05 mg/kg. Good intubation conditions can be expected within 1.5 to 2 min following 3- to 4-times the ED₉₅. Thereafter is takes about 65 min for T1 to recover to 25% of control. Maintenance doses of 0.02 to 0.04 mg/kg have a duration of action of 15 to 20 min. An infusion of cisatracurium of 1.0 to 2.0 mcg/kg/min, is adequate to maintain a 90 to 95% neuromuscular block. The time of recovery is largely independent on the total dose of cisatracurium administered by either repeated injection or infusion. – Mivacurium is a racemate of 3 stereoisomeres of which the trans-trans- and the cis-trans-compound account for 95% of the neuromuscular blocking effect. In adults the ED₉₅ is 0.08 mg/kg. The ensuing recovery of T1 to 25% of control is about 15 min. Rapid injection of 3×ED₉₅ may transiently lower the arterial blood pressure and may produce skin flushing in an incidence of 30 to 40%. Larger doses should be injected slowly with 30 to 60 s. The onset of mivacurium neuromuscular block following 3×ED₉₅ is relatively slow (2 min). Maintenance doses of 0.05 to 0.1 mg/kg have a duration of action of 5 to 10 min. A 95% neuromuscular block may be maintained by an infusion of 3 to 12 μg/kg/min. The time of recovery does not depend on the total cumulative dose given by either repeated injection or by infusion. The duration of mivacurium neuromuscular block may be drastically prolonged in the presence of low or atypical plasmacholinesterase. Both neostigmine and edrophonium are suitable reversal agents. ? None of the presently available benzylisochinoline muscle relaxants has the potential to completely replace succinylcholine.     

The agreement between adductor pollicis mechanomyogram and first dorsal interosseous electromyogram

The agreement between evoked adductor pollicis mechanomyogram and first dorsal interosseous evoked electromyogram (EMG) was evaluated during a pharmacodynamic study of rocuronium and vecuronium. In the first place the effective doses of rocuronium producing 50% and 90% block (ED₅₀ and ED₉₀, respectively) were established in 32 neurolept anaesthetized patients from the adductor pollicis mechanomyogram and the first dorsal interosseous EMG area and amplitude. Secondly, limits of agreement between the two methods were evaluated from the mean difference between methods 2 s.d. in 20 patients during onset of block following 2 × ED₉₀ of rocuronium and vecuronium, and during recovery from the last supplementary dose of 1/2 × ED₉₀. Limits of agreement show how much the EMG may be above or below the mechanomyogram. No differences were found between mechanomyographical and EMG based ED₅₀ (0.20 mg kg^-1) and ED₉₀ (0.30–0.32 mg kg^-1), respectively. The first EMG train–of–four (TOF) response overestimated block at 25% recovery and underestimated block at 75% and 90% recovery by only 3–7%. Limits of agreement suggested that the EMG may be 7–8% above or below the mechanomyogram during onset compared to 12–17% during recovery. The EMG TOF ratio lagged behind that of the mechanomyogram by 0.05 at TOF ratios below 0.50. No difference was found between methods at a TOF ratio of 0.75. Limits of agreement indicated that the EMG TOF ratio may be 0.12–0.15 above or below that of the mechanomyogram. Agreement between the amplitude and the area of the EMG were better than between the mechanomyogram and the EMG. Evaluation of the time courses of action showed that rocuronium had a faster onset of action than vecuronium (1.8 min compared to 2.8 min) while duration of action and reversal were similar. In conclusion, the first dorsal interosseous EMG amplitude and area can be used to assess rocuronium and vecuronium block.     

Mivacurium chloride—a comparative profile

Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline type. Its short duration of action is due to rapid breakdown by plasma cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch response (ED₉₅) is between 60 and 80 μg/kg. Thus, mivacurium is 0.8 times and four times as potent as vecuronium and atracurium, respectively. With 2–3×ED₉₅, tracheal intubation can be accomplished within 2.5 min of intravenous injection. The ensuing DUR25% (time from injection to 25% recovery of control twitch tension) is twice as long as with suxamethonium and about half as long as with equipotent doses of atracurium or vecuronium. For muscle relaxation during long surgical procedures, mivacurium has been used as a continuous infusion. The average 6-min recovery index after infusion of mivacurium is particularly favourable for flexible control of muscle paralysis, whereas the recovery indices after infusion of atracurium or vecuronium are 15–30 min. In conclusion, mivacurium will close the pharmacodynamic gap between suxamethonium and the nondepolarizing muscle relaxants of intermediate duration of action. It will probably also be a suitable alternative to suxamethonium in elective cases.     

Visual estimation of onset time at the orbicularis oculi after five muscle relaxants: application to clinical monitoring of tracheal intubation.

The onset time of neuromuscular blockade at the adductor pollicis (AP) is different among neuromuscular blocking drugs, but these discrepancies had never been studied at the orbicularis oculi (OO). The purpose of this study was to verify if the differences in onset time observed at the AP still existed at the OO and to score the intubating conditions using monitoring at the OO after five muscle relaxants. The study included 172 adults aged 18-75 yr. Anesthesia was induced with fentanyl and propofol. Atracurium (0.5 mg/kg), mivacurium (0.20 mg/kg), rocuronium (0.6 mg/kg), succinylcholine (1.0 mg/kg), or vecuronium (0.08 mg/kg) was injected by random allocation. Time to complete disappearance of the response at the OO was assessed visually after train-of-four stimulation of the facial nerve. Laryngoscopy was then performed, and intubating conditions were determined on a scale of 1-4. Results were based on 150 patients. Onset time at the OO was (mean +/- SD): succinylcholine (57 +/- 17 s) < mivacurium (99 +/-19 s) = rocuronium (99 +/- 47 s) < atracurium (129 +/-33 s) = vecuronium (135 +/- 38 s) (P < 0.05). Overall intubating conditions were excellent (84%), good (14%), poor (1.3%), impossible (0.7%), and were similar among the five groups. We conclude that differences in onset time of muscle relaxants observed at the AP were also found at the OO. Visual estimation of the response at the OO correctly predicted good-to-excellent intubating conditions in more than 90% of cases for all the currently available muscle relaxants. IMPLICATIONS: Onset time of neuromuscular blockade, as estimated visually at the orbicularis oculi, depends on the muscle relaxants given. Regardless of the relaxant used, intubating conditions at loss of orbicularis oculi are acceptable.     

Atracurium, vecuronium and pancuronium. Results of a polygraphic study

The Authors have studied three nondepolarizing muscle relaxants widely used: pancuronium v/s atracurium and vecuronium. The Train of Four was used to detect the magnitude of the neuromuscular blockade. The intubation follows 90 minutes after administration of the drugs and for each patient the Authors valued: 1) the T1 and TR values at intubation; 2) the onset-time; 3) the duration of neuromuscular blockade; 4) the recovery time. Furthermore, the degree of neuromuscular blockade was clinically checked both at the time of induction and at recovery. The results of the present study show, in accordance with the literature, that all three drugs tested are capable of obtaining complete muscle relaxation. Atracurium and vecuronium particularly allow an adequate intubation at the adopted doses (0.6 mg/kg and 0.1 mg/kg respectively) with a relatively short onset-time (medium values 136" in the group of atracurium and 146" in the group of vecuronium) and a restoration time faster than pancuronium.