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).     

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.     

Intubationsbedingungen nach Gabe von Atracurium und Vecuronium Bolusmethode vs. Primingtechnik

Prompted by the ongoing discussion of the pros and cons of using succinylcholine, this study was conducted to compare the responses to bolus injections of atracurium or vecuronium with those after sequential injection of these drugs (priming principle). We evaluated the earliest possible intubation times, intubating conditions, and the onset times (i.e. times from the end of injection to the maximum blockade) under conditions approaching real use as closely as possible. Methods. The randomized and double-blind study was carried out with 80 ASA risk class 1 and 2 patients. Approval of the institutional ethics committee was obtained, and each patient gave informed consent. Patients were randomly allocated to four study groups of 20 patients each. Isotonic saline was administered to those patients assigned to the atracurium or vecuronium bolus groups, whereas the patients assigned to the other two groups received a priming injection of either atracurium (0.05 mg/kg) or vecuronium (0.01 mg/kg). We observed the patients for signs of incipient muscular weakness before the induction of anaesthesia. Anaesthesia was induced with thiopental 3.5 min after the first injection (5 mg/kg and 50–100?mg before intubation). After a further 1 min during which adequate mask ventilatin with oxygen was assured, corresponding to a priming interval of 4.5?min, 0.5 mg/kg of atracurium or 0.1 mg/kg of vecuronium was administered to the patients in the bolus groups and 0.45 mg/kg of atracurium or 0.09 mg/kg of vecuronium as intubating doses to those in the priming groups. Intubation was attempted at 90, 120, 150 and 180?s thereafter. Intubating conditions were evaluated on the basis of laryngoscopy, vocal cord movement and coughing or bucking of the patients. Neuromuscular function was monitored via accelerometry at the adductor pollicis muscle (TOF stimulation of the ulnar nerve every 15?s). Results. The priming doses did not diminish the elicited twitches of the adductor pollicis muscle, but led to heavy eyelids and double vision in 35% of the atracurium patients and 47% of the vecuronium patients; these symptoms were well tolerated by the patients. At the time of intubation the adductor pollicis muscle was relaxed to approximately the same degree in all groups (mean±SD for the TOF ratios in the bolus groups was 0.46±0.37 for atracurium, 0.45±0.4 for vecuronium; in the priming groups 0.52±0.39 for atracurium, 0.53±0.36 for vecuronium). The administration of the relaxants in divided doses significantly shortened the intubating time after atracurium (100 vs 124?s) and improved the intubating conditions of vecuronium (good vs tolerable), but had no effect on the time course of the neuromuscular blockade (onset times in the bolus groups 224±84?s for atracurium and 209±64 s for vecuronium; in the priming groups 249±112?s for atracurium and 205±52 s for vecuronium). Conclusions. The priming technique presented here is clinically superior to the bolus method and therefore should be preferred in all elective cases and in those patients in whom succinylcholine is contraindicated.     

Neuromuscular block: atracurium and vecuronium compared and combined

The neuromuscular blocking action of atracurium and vecuronium acting separately and in combination have been compared using the evoked EMG of the adductor pollicis muscle. Dose response curves have been drawn for the drugs given separately and found to be nonparallel (P less than 0.05). Atracurium was calculated to be 5.25 and 4.1 times less potent than vecuronium, ED50 and ED95 respectively. The effect on neuromuscular transmission of a combined medication using equipotent doses of atracurium and vecuronium, determined from the dose response plots, was found to be greater than would be expected by addition of their separate actions. The combination of small doses resulted in significant neuromuscular blockade.     

Comparison of the effects of mivacurium on the diaphragm and geniohyoid muscles

Although subjects often report difficulty with swallowing shortly after receiving neuromuscular blocking agents, difficulty with swallowing during recovery from neuromuscular blocking agents appears to be infrequent. We have used electromyography to compare onset and recovery at the diaphragm and geniohyoid airway muscles after an intubating dose of mivacurium (0.2 mg kg-1) to determine if the geniohyoid muscles were particularly sensitive to neuromuscular blocking agents. Twelve adults undergoing elective surgery were anaesthetized with propofol and fentanyl and the trachea intubated without neuromuscular blocking agents. The left hypoglossal and right phrenic nerves were stimulated with percutaneous needle electrodes and the electromyogram recorded with surface electrodes. EMG responses were measured after a bolus dose of mivacurium 0.2 mg kg-1. Recordings were also made of the mechanical response of the adductor pollicis to supramaximal ulnar nerve stimulation. There was no difference in the rate of onset of block for geniohyoid muscles and the diaphragm, but recovery to 25% and 90% of the control response was shorter at the diaphragm (median 14.5 (95% confidence limits 12.9-15.3) min and 23.8 (21.7-26) min) than at the geniohyoid muscle (19.4 (15.6-20.1) min and 29.2 (26.3-31.4) min), respectively (P < 0.05). When the train-of-four ratio of the mechanical response of the thumb reached 70%, the diaphragm and geniohyoid muscles had recovered completely in all patients.      

Pharmacokinetic Origin of Carbamazepine-induced Resistance to Vecuronium Neuromuscular Blockade in Anesthetized Patients

Background: Patients receiving chronic carbamazepine therapy have shortened recovery times from a neuromuscular block induced by vecuronium. The current study investigates the pharmacokinetic or pharmacodynamic mechanisms responsible for this observation.

Methods: Pharmacokinetics and pharmacodynamics of 0.1 mg/kg intravenous bolus vecuronium in ten epileptic patients receiving chronic carbamazepine therapy were compared to that of ten control subjects. All patients were scheduled for neurosurgery while anesthetized with isoflurane and sufentanil. Arterial blood samples were collected for 6 h. Plasma vecuronium concentrations were measured by high-performance liquid chromatography coupled to electrochemical detection. The adductor pollicis force of contraction was recorded after supramaximal ulnar nerve stimulation. Plasma vecuronium concentrations were fitted to a two-compartment pharmacokinetic model, and the effect compartment equilibration rate constant was derived with a nonparametric link model. The effect compartment concentrations were fitted to a sigmoid Emax model. Results were compared using Student's t-test for independent samples.

Results: ln the carbamazepine group, the mean recovery times to T1 25% were shorter (28.1+/-3.4 vs. 47.3+/-5.1 min in control subjects; P = 0.007), and the T1 25% to T1 75% recovery index was decreased (7.6+/-1.2 vs. 21.9+/-6.8 min in control subjects; P = 0.025). No changes in onset times were observed. Clearance was 9.0+/-1.2 ml *symbol* kg sup -1 *symbol* min sup -1 versus 3.8+/-0.3 in the control group (P = 0.003), whereas no changes in volumes of distribution at steady-state were observed. Therefore, the mean residence time was halved (17.8+/-2.5 vs. 31.9+/-2.5 min in control subjects; P = 0.001). No differences in the effect compartment equilibration rate constant, vecuronium effect compartment concentration present at a 50% block (EC50), or slope of the sigmoid between the two groups were found.     

The neuromuscular blocking effect of vecuronium on the human diaphragm

This study compares the neuromuscular blocking effect of vecuronium (0.1 mg/kg) on the diaphragm and the adductor pollicis in nine anesthetized patients. Monitoring of the diaphragm consisted of measurement of the transdiaphragmatic pressure after bilateral phrenic nerve stimulation. Onset time for neuromuscular blockade of the diaphragm was 1.6 +/- 0.3 min (+/-SD) compared to 2.5 +/- 0.3 min in the adductor pollicis (P less than 0.001). The diaphragm recovered earlier and more rapidly than the adductor pollicis. The twitch height (TH) returned to 25% of its control value after 27 +/- 8 min for the diaphragm, compared to 41 +/- 11 min for the adductor pollicis (P less than 0.01). Complete TH recovery was achieved after 49 +/- 14 min for the diaphragm and after 74 +/- 22 min for the adductor pollicis (P less than 0.01). The recovery index of 12 +/- 4 min for the diaphragm was significantly shorter (P less than 0.05) than for the adductor pollicis (20 +/- 9 min.) We conclude that monitoring of peripheral muscles in anesthetized patients given vecuronium provides adequate information about the degree of paralysis of the diaphragm.     

Dose-response relationships for edrophonium and neostigmine as antagonists of atracurium and vecuronium neuromuscular blockade

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.     

Facilitation of rapid-sequence intubation with large-dose vecuronium with or without priming.

STUDY OBJECTIVES: To determine the effect of priming on the intubation and onset times of vecuronium 0.3 mg/kg. DESIGN: Randomized, unblinded study. SETTING: Operating rooms and postanesthetic recovery unit of a university-affiliated general hospital. PATIENTS: Thirty female ASA physical status I and II patients scheduled for intraperitoneal surgery divided into two groups of 15 each. INTERVENTIONS: Anesthesia was induced and maintained with sufentanil, droperidol, thiopental sodium, and nitrous oxide in oxygen. Patients in Group 1 were given vecuronium 0.015 mg/kg 4 minutes before induction and vecuronium 0.285 mg/kg 1 minute after induction. Patients in Group 2 received a single 0.3 mg/kg dose of vecuronium 1 minute after thiopental sodium. The ulnar nerve was stimulated every 10 seconds with train-of-four supramaximal impulses of 0.2 millisecond duration at 2 Hz. The compound electromyogram (EMG) of the adductor pollicis was continuously recorded. The trachea was intubated when the amplitude of the EMG decreased to 15% to 25% of control. At the end of surgery, residual neuromuscular block was reversed with edrophonium 0.75 mg/kg. MEASUREMENTS AND MAIN RESULTS: All patients in Group 1 could be intubated in 80 seconds or less, and the longest onset time was 120 seconds. In Group 2, the longest intubation time was 140 seconds, and the longest onset time was 200 seconds. Clinical durations in both groups were unpredictable, ranging from 47 to 185 minutes in Group 1 and from 63 to 160 minutes in Group 2. Ten of the 30 patients required an additional 0.5 mg/kg of edrophonium for antagonism of the residual neuromuscular block. There were no significant changes in heart rate or blood pressure attributable to vecuronium. CONCLUSIONS: Seventy-five percent to 85% neuromuscular block of the adductor pollicis, required for atraumatic tracheal intubation, developed in 80 seconds or less when vecuronium 0.3 mg/kg was administered in divided doses and in 140 seconds or less when it was injected as a single bolus dose. Clinical duration of vecuronium 0.3 mg/kg is long and unpredictable, and reversal of residual neuromuscular block may require larger doses of anticholinesterases. It is recommended that an intubating dose of vecuronium 0.3 mg/kg be used only in patients undergoing long surgical procedures that require prolonged postanesthetic mechanical ventilation.     

The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

Monitoring orbicularis oculi predicts good intubating conditions after vecuronium in children

Purpose

The aim of the study was to compare visual estimation of onset of neuromuscular blockade at both the adductor pollicis (AP) and the orbicularis oculi (OO) in children and to determine if monitonng the OO could predict good intubating conditions during vecuronium-induced neuromuscular blockade.

Methods

Thirty ASA I–II children (1.5–9 yr) were studied. Anaesthesia was induced with 6–8 mg · kg^?1 thiopentone. The ulnar nerve at the wrist and the temporal branch of the facial nerve were stimulated every 10 sec using train of-four (TOF) stimuli. Vecuronium. 0.15 mg · kg, was administered as a bolus. The responses at both the OO and the AP were evaluated visually. Patients were randomly divided into two groups. In the AP group (n = 15), the trachea was intubated when the AP was completely blocked. In the OO group (n = 15), intubation was performed when the OO was completely blocked. Intubating conditions were scored on a scale of 1 to 4.

Results

All the patients had complete blockade at both the orbicularis oculi and the adductor pollicis. In the two groups, time from injection of vecuronium to complete neuromuscular blockade was shorter at the orbicularis oculi than at the adductor pollicis, 1.5 ± 0.5 min vs 2.3 ± 0.7 min, respectively, (P < 0.05; mean ± SD) in the AP group, 1.7 ± 0.3 min vs 2.3 ± 0.8 min, respectively, in the OO group (P < 0.05). Intubating conditions were excellent in all patients except one. where it was rated as good. They did not differ between groups.

Conclusion

Following administration of 0.15 mg · kg^?1 vecuronium in children, monitoring of the OO can detect good intubating conditions 0.7 min earlier than with monitoring of the AP.     

Comparison of duration of neuromuscular blocking effect of atracurium and vecuronium in young and elderly patients

In a controlled, randomized study, we evaluated duration ofneuromuscular block in 80 patients undergoing routine abdominalsurgery. Forty patients were aged 18–50 yr (control group)and 40 patients were more than 65 yr (elderly group). All patientshad normal plasma creatinine concentrations. After inductionof anaesthesia, patients were allocated randomly to receiveeither atracurium 0.5 mg kg^–1 or vecuronium 0.1 mg kg^–1to facilitate tracheal intubation. Monitoring of the evokedresponse of the adductor pollicis muscle to supramaximal singletwitch ulnar nerve stimulation every 10 s was performed andmeasured with a strain gauge. Repeat doses of atracurium 0.1mg kg^–1 or vecuronium 0.02 mg kg^–1 were administeredwhen the adductor pollicis response recovered to 25% of thecontrol twitch height. We found that the duration of actionof the initial dose of atracurium was similar in the controland elderly groups, and it did not vary after repeated doses.However, the initial dose of vecuronium caused a significantlylonger period of clinical block in the elderly group comparedwith the controls, and the duration of action of repeated doseswas longer in the elderly group. We conclude that as there isa risk of prolonged effect of vecuronium in the elderly, monitoringof neuromuscular function is recommended in this group. Alternatively,atracurium should be preferred for prolonged surgery in elderlypatients.     

Neuromuscular monitoring at the orbicularis oculi may overestimate the blockade in myasthenic patients

BACKGROUND: In most publications about myasthenia, monitoring neuromuscular blockade during anesthesia is recommended. In healthy patients, the relation of blockade between muscles has been established, but there is little information about the relation in myasthenic patients. Our objective was to investigate whether the relation between the orbicularis oculi and adductor pollicis muscles is the same in healthy patients and myasthenic patients. METHODS: After anesthesia was induced with 4-6 mg/kg thiopental and 2 microg/kg fentanyl, followed by 2% sevoflurane and 60% nitrous oxide in oxygen, 10 healthy patients and 10 myasthenic patients received 0. 025 and 0.01 mg/kg vecuronium, respectively. Neuromuscular monitoring was performed with use of accelerometry at the orbicularis oculi and the adductor pollicis muscles by stimulating the temporal branch of the facial nerve and the ulnar nerve. RESULTS: The relation of blockade between these two muscles was not the same in healthy patients and myasthenic patients: in healthy patients, the maximum neuromuscular blockade with 0.025 mg/kg vecuronium was less in the orbicularis oculi than in the adductor pollicis (median 72% vs. 91%; P < 0.05); in contrast, in myasthenic patients, the blockade with 0.01 mg/kg vecuronium was greater in the orbicularis oculi than in the adductor pollicis (median 96% vs. 62%; P < 0.05). CONCLUSION: Neuromuscular monitoring at the orbicularis oculi may overestimate blockade in myasthenic patients. Extubation must be performed when the muscle most sensitive to neuromuscular blocking agents is recovered. Therefore, neuromuscular monitoring at the orbicularis oculi is recommended to avoid persistent neuromuscular blockade in patients with myasthenia gravis.     

Potency of pancuronium at the diaphragm and the adductor pollicis muscle in humans

The measurement of force of contraction of the adductor pollicis muscle following supramaximal stimulation of the ulnar nerve has become a standard method to assess the effect of neuromuscular blocking drugs. However, the diaphragm is regarded as resistant to these drugs, and considerable residual respiratory power might still be present after total block of adductor pollicis function. To quantify this differential effect, train-of-four stimulation was applied to the ulnar and the phrenic nerves in patients under N2O-halothane anesthesia. The force of contraction of the adductor pollicis muscle was measured with a force-displacement transducer and compared with the diaphragmatic electromyogram (EMG). Pancuronium cumulative dose-response curves for both muscles were determined in 10 ASA Class I adults. The mean dose (+/- SEM) required to depress adductor pollicis and diaphragm responses to first twitch stimulation (ED50) was 29.5 +/- 3.5 micrograms/kg and 59.5 +/- 7.0 micrograms/kg, respectively. Corresponding values for ED90 were 45 +/- 5 micrograms/kg and 95 +/- 11 micrograms/kg, respectively, indicating that the diaphragm required approximately twice as much pancuronium as the adductor pollicis block, the diaphragm was only 24 +/- 4% blocked. It is concluded that the adductor pollicis response might underestimate the degree of diaphragmatic relaxation. On the other hand, the administration of pancuronium in a dose sufficient to produce total paralysis might result in the inability to antagonize neuromuscular block in all muscles.     

Clinical,electrical and mechanical correlations during recovery from neuromuscular blockade with vecuronium

In order to determine correlations between electromyographic (EMG), mecanomyographic (MMG) and clinical criteria of adequate recovery from neuromuscular blockade with vecuronium, seven young healthy conscious volunteers were given subparalysing doses of vecuronium. During recovery from neuromuscular blockade, vital capacity, negative inspiratory pressure, peak expiratory flow rate and five-second head lift were assessed. Neuromuscular monitoring included the evoked EMG response of the adductor digiti minimi and the simultaneous evoked MMG response of the adductor pollicis on the same side. We found that all subjects maintained head lift for five seconds at EMG T4T1 of 0.70, and they achieved normal respiratory tests at EMG T4/T1 of 0.90. The MMG T4/T1 needed for the subjects to perform normal respiratory tests was found to be 0.50, at which time six of the seven subjects were able to perform adequately the head lift test.     

Neuromuscular Monitoring at the Orbicularis Oculi May Overestimate the Blockade in Myasthenic Patients

Background: In most publications about myasthenia, monitoring neuromuscular blockade during anesthesia is recommended. In healthy patients, the relation of blockade between muscles has been established, but there is little information about the relation in myasthenic patients. Our objective was to investigate whether the relation between the orbicularis oculi and adductor pollicis muscles is the same in healthy patients and myasthenic patients.

Methods: After anesthesia was induced with 4-6 mg/kg thiopental and 2 [mu]g/kg fentanyl, followed by 2% sevoflurane and 60% nitrous oxide in oxygen, 10 healthy patients and 10 myasthenic patients received 0.025 and 0.01 mg/kg vecuronium, respectively. Neuromuscular monitoring was performed with use of accelerometry at the orbicularis oculi and the adductor pollicis muscles by stimulating the temporal branch of the facial nerve and the ulnar nerve.

Results: The relation of blockade between these two muscles was not the same in healthy patients and myasthenic patients: in healthy patients, the maximum neuromuscular blockade with 0.025 mg/kg vecuronium was less in the orbicularis oculi than in the adductor pollicis (median 72%vs. 91%;P < 0.05); in contrast, in myasthenic patients, the blockade with 0.01 mg/kg vecuronium was greater in the orbicularis oculi than in the adductor pollicis (median 96%vs. 62%;P < 0.05).     

Enzymatic Versus Pharmacologic Antagonism of Profound Mivacurium-induced Neuromuscular Blockade

Background: Mivacurium, a nondepolarizing muscle relaxant, is hydrolyzed by butyrylcholinesterase. The use of butyrylcholinesterase for antagonism of profound mivacurium-induced blockade has not been studied in humans. In part 1 of this two-part study, the authors examined the relationship between the posttetanic count (PTC) and recovery from profound mivacurium-induced blockade. In part 2, an attempt was made to antagonize a quantified level of profound mivacurium-induced blockade using either butyrylcholinesterase, edrophonium, or neostigmine.

Methods: Eighty-seven ASA physical status 1 or 2 adult patients were given 0.15 mg *symbol* kg sup -1 mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. They were randomly assigned to eight groups. Neuromuscular function was monitored by recording the mechanomyographic response of the adductor pollicis to PTC and train-of-four (TOF) stimulation in all patients except those in group 1 where the TOF was the only pattern used. In part 1, neuromuscular function was allowed to recover spontaneously in ten patients (group 1; control-TOF) until TOF ratio (the amplitude of the fourth evoked response as a fraction of the first evoked response: T4/T1) had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 21 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously until TOF ratio had reached 0.75 (group 2; control-PTC). In part 2, the antagonism of mivacurium-induced profound (PTC greater or equal to 1; groups 3-6) and 90% block (groups 7-8) of twitch height were investigated in another 56 patients. Groups 3 and 7 received neostigmine 0.06 mg *symbol* kg sup -1 whereas groups 4 and 8 received edrophonium 1 mg *symbol* kg sup -1, respectively. Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to activity present in 25 or 70 ml *symbol* kg sup -1 of human plasma, respectively.

Results: Neither butyrylcholinesterase nor edrophonium shortened the times from first PTC response to TOF = 0.75 compared to group 2. Neostigmine resulted in prolongation of recovery time. There was a linear relationship (r = -0.80; P = 0.00001) between PTC and time of onset of TOF response.     

Pharmacokinetics of Cisatracurium in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia

Background: Cisatracurium, one of the ten isomers in atracurium, is a nondepolarizing muscle relaxant with an intermediate duration of action. It is more potent and less likely to release histamine than atracurium. As one of the isomers composing atracurium, it presumably undergoes Hofmann elimination. This study was conducted to describe the pharmacokinetics of cisatracurium and its metabolites and to determine the dose proportionality of cisatracurium after administration of 2 or 4 times the ED95.

Methods: Twenty ASA physical status 1 or 2 patients undergoing elective surgery under nitrous oxide/opioid/barbiturate anesthesia were studied. Patients received a single rapid intravenous bolus dose of 0.1 or 0.2 mg *symbol* kg sup -1 (2 or 4 times the ED95, respectively) cisatracurium. All patients were allowed to recover spontaneously to a train-of-four ratio greater or equal to 0.70 after cisatracurium-induced neuromuscular block. Plasma was extracted, acidified, and stored frozen before analysis for cisatracurium, laudanosine, the monoquaternary acid, and the monoquaternary alcohol metabolite.

Results: The clearances (5.28+/-1.23 vs. 4.66+/- 0.67 ml *symbol* min sup -1 *symbol* kg sup -1) and terminal elimination half-lives (22.4+/-2.7 vs. 25.5+/-4.1 min) were not statistically different between patients receiving 0.1 mg *symbol* kg sup -1 and 0.2 mg *symbol* kg sup -1, respectively. Maximum concentration values for laudanosine averaged 38+/-21 and 103+/-34 ng *symbol* ml sup -1 for patients receiving the 0.1 and 0.2 mg *symbol* kg sup -1 doses, respectively. Maximum concentration values for monoquaternary alcohol averaged 101+/-27 and 253+/-51 ng *symbol* ml sup -1, respectively. Monoquaternary acid was not quantified in any plasma sample.     

Ketamine potentiates nondepolarizing neuromuscular relaxants in a primate

Ketamine has many neuromuscular effects in vitro. Its neuromuscular effects in vivo have been controversial and inconsistent. To systematically examine its neuromuscular effects over a wide dose range and its interaction with all popular nondepolarizing neuromuscular relaxants, the effects of ketamine 2, 5, and 10 mg/kg IV were studied on a continuous but incomplete (50%) neuromuscular block preestablished by an IV infusion of d-tubocurarine, atracurium, vecuronium, and pancuronium. Indirectly stimulated adductor pollicis muscle response of monkeys anesthetized with 0.5-1.0% halothane in oxygen were quantified. Ketamine in the absence of a neuromuscular relaxant had no effect on the thumb twitch. In a dose-dependent manner, ketamine significantly enhanced the 50% depression of the thumb twitch preestablished by a constant IV infusion of each of the four muscle relaxants studied. Ketamine 2 mg/kg potentiated the neuromuscular relaxants in the following order of magnitude: vecuronium greater than atracurium greater than d-tubocurarine greater than pancuronium. However, with a 10 mg/kg dose of ketamine, pancuronium became as potentiated as was vecuronium, i.e., pancuronium = vecuronium greater than atracurium greater than d-tubocurarine. It is concluded that in the primate, ketamine potentiates all nondepolarizing muscle relaxants in a dose-dependent manner.     

Facilitation of rapid endotracheal intubations with divided doses of nondepolarizing neuromuscular blocking drugs

The authors sought to determine whether prior administration of a small, subparalyzing dose of nondepolarizing muscle relaxant would shorten the onset time of an intubating dose of muscle relaxant. Initially, in 60 anesthetized patients, twitch response of adductor pollicis to ulnar nerve stimulation was studied after a small dose of pancuronium 0.015 mg . kg-1, metocurine 0.03 mg . kg-1, or d-tubocurarine 0.04 mg . kg-1, followed 3 min later by pancuronium 0.08 mg . kg-1 or atracurium 0.4 mg . kg-1 administered iv. After 60 s, the minimum neuromuscular block, in all patients was 79.0 +/- 5.0%. A 95% depression or twitch tension occurred between 59.1 +/- 5.3 and 86.1 +/- 5.9 s. In another 60 patients, intubating conditions under similar regimen were studied, except the small dose of muscle relaxant was given immediately prior to induction of anesthesia. At the end of 60 s, good to excellent intubating conditions were present in 100% of the patients following the second dose of pancuronium and in 83% of the patients following atracurium. In 17% of the patients, after atracurium intubating conditions were fair. When nondepolarizing neuromuscular blocking drugs are administered in divided doses, neuromuscular blockade adequate for endotracheal intubation is achieved in less than 90 s. This facilitates rapid endotracheal intubation in a time comparable to using succinylcholine, without undesirable effects of the depolarizing neuromuscular blocking drugs.