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.     

Onset properties of mivacurium measured by mechanomyography depend on the twitch height of the adductor pollicis muscle

INTRODUCTION: The influence of the twitch height of the adductor pollicis muscle during baseline measurements on the pharmacodynamic parameters of mivacurium was prospectively evaluated. PATIENTS AND METHODS: Fifty adult patients were anaesthetized with propofol and alfentanil. Neuromuscular function was monitored mechanomyographically by measuring the force of the adductor pollicis muscle following stimulation of the ulnar nerve. Following a stabilization period of 20 min, the individual twitch height of the adductor pollicis muscle was determined before a single bolus of mivacurium (75 microg kg-1) was administered. Patients were divided into two groups. The data of patients whose thumb adduction force was below the median value of all patients were the 'low force' group (9.1 +/- 1.4 N) and the data of all other patients were the 'high force' group (13.7 +/- 1.8 N). RESULTS: In the 'high force' group, maximum neuromuscular blockade of mivacurium was deeper (0.97 +/- 0.05 vs. 0.93 +/- 0.06; P < 0.05) and onset faster (2.9 +/- 1.1 min vs. 4.0 +/- 1.2 min; P < 0.05). Neuromuscular recovery did not differ between the groups. CONCLUSION: The different onset speeds reflect either different sensitivity to neuromuscular blocking agents with respect to patients' muscle power or a problem of the mechanomyographic measuring technique.     

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.     

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.     

A comparison of the neuromuscular blocking effects and reversibility of cisatracurium and atracurium

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mgkg⁻¹ were compared with those of atracurium 0.5 mgkg⁻¹ during anaesthesia with propofol, nitrous oxide and isoflurane. Neuromuscular block was monitored using train-of-four stimulation while recording the mechanomyographic response of the adductor pollicis muscle. The block was either allowed to recover spontaneously or was antagonised with neostigmine 50 μgkg⁻¹ at 10% or 25% recovery of the first twitch of the train-of-four. The median times to maximum block were 2.7, 2.2 and 1.5 min following cisatracurium 0.1 and 0.15 mgkg⁻¹ and atracurium 0.5 mgkg⁻¹, respectively. After cisatracurium 0.1 mgkg⁻¹ had been given, the median time to recovery of the train-of-four ratio to 0.8 ('adequate recovery') was 74 min during spontaneous recovery, 48 min after reversal with neostigmine when the first twitch of the train-of-four had returned to 10% of control and 50 min after reversal when the first twitch of the train-of-four had returned to 25% of control. These times for cisatracurium 0.15 mgkg⁻¹ and atracurium 0.5 mgkg⁻¹ were 90, 66 and 57 min and 75, 56 and 54 min, respectively. Administration of neostigmine significantly shortened the time to adequate recovery for both drugs but there were no significant differences in the case of either neuromuscular blocking drug between the groups of patients given neostigmine at 10 or 25% recovery of the first twitch of the train-of-four.     

Mivacurium infusion during nitrous oxide-isoflurane anesthesia: a comparison with nitrous oxide-opioid anesthesia.

STUDY OBJECTIVE: To determine the potentiation of the neuromuscular blockade induced by a titrated infusion of mivacurium in the presence of isoflurane versus a nitrous oxide (N2O)-opioid anesthesia. DESIGN: An open-label, controlled study. SETTING: The inpatient anesthesia service of two university medical centers. PATIENTS: Thirty adults divided into two groups. INTERVENTION: An intravenous infusion of mivacurium during anesthesia with N2O-opioid or N2O-isoflurane. MEASUREMENTS AND MAIN RESULTS: A neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. The mivacurium infusion rate was significantly less in the presence of isoflurane [4.0 +/- 0.8 micrograms/kg/min (mean +/- SEM)] than during N2O-opioid anesthesia (6.4 +/- 0.6 micrograms/kg/min). The recovery rates did not differ between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 of at least 0.75 occurred in an average of 17.9 +/- 1.5 minutes, with a mean recovery index (T25-75) of 6.0 +/- 0.7 minutes. CONCLUSION: Isoflurane anesthesia reduces the infusion rate of mivacurium required to produce about 95% depression of neuromuscular function.     

Blood flow and mivacurium-induced neuromuscular block at the orbicularis oculi and adductor pollicis muscles

We have studied the pattern of blood flow and pharmacodynamic profile of mivacurium-induced block at the adductor pollicis and orbicularis oculi muscles. We studied 30 adult patients anaesthetized with fentanyl, thiopentone, nitrous oxide-isoflurane, and mivacurium 0.2 mg kg-1. Neuromuscular transmission was monitored with accelerometry (TOF Guard, Biometer, Denmark). Blood flow was measured at the two muscles with the use of a laser Doppler flowmeter (Laserflo BPM2, Vasamedics, USA). All patients developed 100% neuromuscular block at the adductor pollicis muscle. Mean maximum neuromuscular block at the orbicularis oculi was 96.4 (SD 3.5)% (ns). Onset time, time required for 25% and 75% recovery of the first twitch in the train-of-four (T1), and a train- of-four ratio (T4/T1) of 90% at the orbicularis oculi were respectively, mean 130.4 (SD 28.5) s, 9.1 (3.2) min, 16.2 (3.9) min and 20.2 (4.3) min and were significantly shorter than the corresponding values at the adductor pollicis: 202.7 (37.2) s, 12.9 (3.9) min, 21.1 (5.1) min and 30.8 (7.4) min. For a given T1, there was significantly less train-of-four fade (T4/T1) at the orbicularis oculi than at the adductor pollicis muscle during recovery. Blood flow was comparable at the two muscles before induction of anaesthesia. Thiopentone significantly increased thenar muscle blood flow from 2.9 (1.5) to 12.3 (6.8) ml 100 g-1 min-1, with a further increase to 22.7 (8.0) ml 100 g- 1 min-1 after isoflurane (P < 0.001). Blood flow at the orbicularis oculi was not altered by thiopentone or isoflurane and was consistently lower than that at the adductor pollicis muscle. We conclude that the different pharmacodynamic profiles of mivacurium-induced block at the orbicularis oculi and adductor pollicis muscles were not related primarily to a difference in blood flows.      

不同剂量顺式阿曲库铵对患者拇内收肌与眼轮匝肌肌松效应的比较

目的 比较不同剂量顺式阿曲库铵对患者拇内收肌与眼轮匝肌的肌松效应.方法 全麻患者25例,ASA Ⅰ或Ⅱ级,年龄42～64岁,体重51～81 kg,随机分为2组,顺式阿曲库铵0.075ms/ks组(Ⅰ组,n=11)和顺式阿曲库铵0.15 mg/kg组(Ⅱ组,n=14).静脉注射咪达唑仑0.035～0.045mg/kg、异丙酚1.5～2 mg/kg、芬太尼0.1～0.2 mg、顺式阿曲库铵0.075 mg/kg或0.15 mg/kg行麻醉诱导,吸入50%氧化亚氮、间断静脉注射芬太尼维持麻醉.采用2台TOF-Watch SX加速度肌松监测仪同步监测眼轮匝肌和拇内收肌的神经肌肉阻滞情况,记录肌松起效时间、无反应期及T25%和T75%恢复时间.于眼轮匝肌肌颤搐抑制75%～80%时行气管插管,并评价气管插管条件.结果 2组气管插管条件良好且差异无统计学意义(P>0.05);与Ⅰ组比较,Ⅱ组拇内收肌和眼轮匝肌肌松起效时间缩短,T25%恢复时间、T75%恢复时间和无反应期延长(P<0.01);与拇内收肌比较,Ⅰ组眼轮匝肌T75%恢复时间缩短,Ⅱ组眼轮匝肌无反应期和T25%恢复时间缩短(P<0.05或0.01).结论 顺式阿曲库铵对拇内收肌和眼轮匝肌的肌松效应呈剂量依赖性,眼轮匝肌对顺式阿曲库铵的敏感性低于拇内收肌;监测顺式阿曲库铵对眼轮匝肌神经肌肉阻滞情况可有效指导气管插管.     

Mivacurium-induced neuromuscular block in adult patients suffering from Charcot-Marie-Tooth disease

PURPOSE: The response to non-depolarizing neuromuscular blocking drugs is variable in patients with Charcot-Marie-Tooth (CMT) disease. We speculated that CMT involvement of the monitored muscle may be partially responsible for this inconsistency. We therefore investigated the response to a standard dose of mivacurium simultaneously assessed at adductor pollicis (AP) and orbicularis oculi (OO) muscles in five patients with CMT. CLINICAL FEATURES: Over a period of one year, five adult patients with CMT scheduled for orthopedic surgery were studied. The right arm and the right supercilliary arch were prepared for acceleromyographic (AMG) neuromuscular monitoring. The AMG probes were attached at the distal interphalangeal joint of the right thumb and on the right upper eyelid to record the response of the AP and OO, respectively. The ulnar nerve and upper part of the facial nerve were stimulated supramaximally with repeated train-of-four stimuli (2 Hz, 0.2 msec) every 15 sec via applied surface electrodes. Following monitor calibration and induction of general anesthesia, mivacurium 0.2 mg x kg(- 1) iv was given, and the time course of relaxation and recovery were assessed. Times to spontaneous recovery of T1 to 25% were 15 +/- 3 vs 12 +/- 4 min in the AP and OO muscle groups respectively, whereas times to 90% recovery were 23 +/- 5 vs 29 +/- 10 min, respectively. CONCLUSION: The onset and recovery characteristics associated with mivacurium-induced neuromuscular block were similar at the AP and OO muscle groups. A near normal response to mivacurium was observed in this small series of patients with CMT disease.     

Effects of mivacurium on the diaphragm evaluated by cervical magnetic stimulation of the phrenic nerves

BACKGROUND AND OBJECTIVE: Non-depolarizing neuromuscular blocking agents have differential effects on the diaphragm and skeletal muscles. We employed a new method to study the effects of mivacurium on the diaphragm and compared the results obtained with this method with published data. METHODS: Anaesthesia was induced and maintained with propofol and alfentanil and the trachea was intubated after topical anaesthesia. Contractions of the diaphragm were induced by cervical magnetic stimulation of the phrenic nerves and quantified by measuring airway pressure responses. The neuromuscular effects on skeletal muscles were measured by acceleromyography of the adductor pollicis muscle. Mivacurium (0.15 mg kg(-1)) was injected and neuromuscular responses were recorded until the effects had waned. RESULTS: Eleven male and 10 female patients (ASA I-II; 57 +/- 16 yr; 78 +/- 13 kg; mean +/- standard deviation) participated. Median maximal reduction of twitch response was less (P < 0.05) for the diaphragm (89%) than for the adductor pollicis (100%). Time to 25% recovery was shorter for the diaphragm than for the adductor pollicis (8.8 +/- 2.2 min vs. 22.6 +/- 5.0 min, P < 0.05). The difference between the recovery index of the diaphragm (7.3 min (3.6-18.4)) and the adductor pollicis (8.2 min (4.4-20.9) (median (range)) just missed our chosen level of statistical significance (P = 0.06). The recovery time to train-of-four 0.8 was shorter for the diaphragm (median and 95% confidence interval 25.1 +/- 10.2 min) than for the adductor pollicis (median and 95% confidence interval 37.5 +/- 9.4 min, P < 0.05). CONCLUSIONS: The duration of the clinical effect of mivacurium on the diaphragm is markedly shorter than on the adductor pollicis muscles but there was only a small difference in the recovery index of the two muscles. These effects and the time courses determined with the new method closely resemble the results obtained with different methods in other studies.     

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).     

Early Reversal of Rapacuronium with Neostigmine

Background: Rapacuronium is a rapid-onset, short-acting neuromuscular relaxant. This multiple-center study determined neuromuscular recovery when neostigmine was given 2 or 5 min after rapacuronium.

Methods: One hundred seventeen patients were randomized to receive two different of rapacuronium and to receive neostigmine in two different does and at two different times. During propofol anesthesia with nitrous oxide, oxygen, and fentanyl, 1.5 or 2.5 mg/kg rapacuronium was given 1 min before tracheal intubation. Neuromuscular block was measured by train-of-four ulnar nerve stimulation every 12 s: The adductor pollicis force of contraction was recorded mechanomyographically. Two or five minutes after rapacuronium was administered, 0.05 or 0.07 mg/kg neostigmine was administered and recovery was compared with that of control patients who received no neostigmine.

Results: Both doses of rapacuronium produced 100% block in all but one patient, who exhibited 97% block. Neostigmine accelerated recovery in all groups. After 1.5 mg/kg rapacuronium, the time to 25% T1 twitch recovery decreased from a mean of 16 min in control patients to mean values of 8-10 min in the treatment groups: The time to train-of-four ratio of 0.7 decreased from 38 min to 17-19 min. After 2.5 mg/kg rapacuronium, the time to 25% T1 was reduced from 23 min to 11-12 min, and the time to train-of-four ratio of 0.7 decreased from 54 min to 26-32 min. Recovery was not different among the groups that received different doses and timing of neostigmine.     

Early reversal of rapacuronium with neostigmine.

BACKGROUND: Rapacuronium is a rapid-onset, short-acting neuromuscular relaxant. This multiple-center study determined neuromuscular recovery when neostigmine was given 2 or 5 min after rapacuronium. METHODS: One hundred seventeen patients were randomized to receive two different doses of rapacuronium and to receive neostigmine in two different doses and at two different times. During propofol anesthesia with nitrous oxide, oxygen, and fentanyl, 1.5 or 2.5 mg/kg rapacuronium was given 1 min before tracheal intubation. Neuromuscular block was measured by train-of-four ulnar nerve stimulation every 12 s: The adductor pollicis force of contraction was recorded mechanomyographically. Two or five minutes after rapacuronium was administered, 0.05 or 0.07 mg/kg neostigmine was administered and recovery was compared with that of control patients who received no neostigmine. RESULTS: Both doses of rapacuronium produced 100% block in all but one patient, who exhibited 97% block. Neostigmine accelerated recovery in all groups. After 1.5 mg/kg rapacuronium, the time to 25% T1 twitch recovery decreased from a mean of 16 min in control patients to mean values of 8-10 min in the treatment groups: The time to train-of-four ratio of 0.7 decreased from 38 min to 17-19 min. After 2.5 mg/kg rapacuronium, the time to 25% T1 was reduced from 23 min to 11-12 min, and the time to train-of-four ratio of 0.7 decreased from 54 min to 26-32 min. Recovery was not different among the the groups that received different doses and timing of neostigmine. CONCLUSIONS: Recovery of intense rapacuronium block was accelerated by early neostigmine administration. When given 2 min after rapacuronium, neostigmine was as effective as after 5 min, and 0.05 mg/kg neostigmine was comparable to 0.07 mg/kg neostigmine.     

Mivacurium infusion requirements in pediatric surgical patients during nitrous oxide-halothane and during nitrous oxide-narcotic anesthesia

We were interested in determining the infusion rate of mivacurium required to maintain approximately 95% neuromuscular blockade during nitrous oxide-halothane (0.8% end-tidal) or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Mivacurium steady-state infusion requirements averaged 315 +/- 26 micrograms.m-2.min-1 during nitrous oxide-halothane anesthesia and 375 +/- 19 micrograms.m-2.min-1 (mean +/- SEM) during nitrous oxide-narcotic anesthesia. Higher levels of pseudocholinesterase activity were generally associated with a higher mivacurium infusion requirement. During both anesthetics, younger age was associated with a higher infusion requirement when the infusion requirement was calculated in terms of micrograms.kg-1.min-1. This difference was not present when the infusion rate was calculated in terms of micrograms.m-2.m-1. There was no evidence of cumulation during prolonged mivacurium infusion. There was no difference in the rates of spontaneous or reversal-mediated recovery between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 greater than or equal to 0.75 occurred in 9.8 +/- 0.4 min, with a recovery index, T25-75, of 4.0 +/- 0.2 min (mean +/- SEM). In summary, pseudocholinesterase activity is the major factor influencing mivacurium infusion rate in children during nitrous oxide-narcotic or nitrous oxide-halothane (0.8% end-tidal) anesthesia.     

Dose-response relations of doxacurium and its reversal with neostigmine in young adults and healthy elderly patients.

Dose-response relationships for doxacurium and neostigmine were established in 24 young (18-40 yr) and 24 elderly (70-85 yr) patients, ASA physical status I or II, anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. Mechanomyographic response of the adductor pollicis muscle to the train-of-four stimulation of the ulnar nerve was recorded. Doxacurium (5, 10, 15, or 20 micrograms/kg IV) was administered by random allocation. After maximal blockade, and additional dose, for a total of 30 micrograms/kg, was administered. When first twitch height recovered to 25%, incremental doses of 5 micrograms/kg were administered for maintenance of relaxation. Neostigmine (5, 10, 20, or 40 micrograms/kg) was injected at 25% first twitch recovery, and neuromuscular monitoring was continued for 10 min. The doses of doxacurium (+/- SEM) required to produce a 50%, 90%, and 95% depression of twitch tension in the young patients were, respectively, 13.3 +/- 1.6, 23.6 +/- 2.8, and 28.6 +/- 3.4 micrograms/kg, not statistically different from corresponding values in the elderly, 11.8 +/- 1.3, 21.2 +/- 2.3, and 25.9 +/- 2.9 micrograms/kg, respectively. Time to 25% recovery after 30 micrograms/kg was 80.2 +/- 12.2 min in the young versus 133.0 +/- 17.1 min in the elderly (P less than 0.05). Neostigmine-assisted recovery was not significantly different in both groups. The estimated doses of neostigmine to obtain 70% train-of-four recovery after 10 min were 53.6 +/- 7.5 micrograms/kg in the young and 41.6 +/- 5.8 micrograms/kg in the elderly (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidurally administered mepivacaine delays recovery of train-of-four ratio from vecuronium-induced neuromuscular block

BACKGROUND: The aim of this study was to examine the efficacy of epidurally administered mepivacaine on recovery from vecuronium-induced neuromuscular block. METHODS: Eighty patients were randomly assigned to one of two study groups. They were either given epidurally a bolus of 0.15 ml kg(-1) of mepivacaine 2%, followed by repetitive injections of 0.1 ml kg(-1) h(-1) throughout the study, or were not given epidurally. General anaesthesia was induced and maintained with fentanyl, propofol and nitrous oxide. Neuromuscular block was induced with vecuronium 0.1 mg kg(-1) and monitored using acceleromyographic train-of-four (TOF) at the adductor pollicis. Patients in each treatment group were randomized to receive neostigmine 0.04 mg kg(-1) at 25% recovery of the first twitch of TOF or to recover spontaneously to a TOF ratio of 0.9. The effect of epidural mepivacaine on speed of spontaneous and facilitated recovery of neuromuscular function was evaluated. RESULTS: The time from administration of vecuronium to spontaneous recovery to a TOF ratio of 0.9 was significantly longer in the epidural mepivacaine group [105.4 (14.2) min] as compared with the control group [78.5 (9.1) min, P < 0.01]. Neostigmine administered at 25% of control in T1 shortened recovery from neuromuscular block, however the time required for facilitated recovery to a TOF ratio of 0.9 in the epidural group was significantly longer than that in the control group [7.6 (1.6) min vs 5.8 (2.1) min, P < 0.01]. CONCLUSIONS: In clinical anaesthesia, it should be recognized that epidurally administered mepivacaine delays considerably the TOF recovery from neuromuscular block.     

Neostigmine,pyridostigmine and edrophonium as antagonists of deep pancuronium blockade

To compare the ability of equipotent doses of neostigmine, pyridostigmine and edrophonium to antagonize intense pancuronium neuromuscular blockade, one hundred and twenty ASA physical status I or II patients scheduled for elective surgery received 0.06 mg.kg-1 pancuronium during a thiopentone nitrous oxide-enflurane anaesthetic. Train-of-four stimulation was applied every 12 s and the force of contraction of the adductor pollicis muscle was recorded. In the first 60 patients, spontaneous recovery was allowed until ten per cent of initial first twitch height. Then neostigmine (0.005, 0.01, 0.02 or 0.05 mg.kg-1), pyridostigmine (0.02, 0.04, 0.1 or 0.2 mg.kg-1), or edrophonium (0.1, 0.2, 0.4 or 1 mg.kg-1) was injected by random allocation. Dose-response relationships were established from the measurement of first twitch height (T1) ten minutes later. From these, neostigmine, 0.04 and 0.08 mg.kg-1 was found to be equipotent to pyridostigmine, 0.2 and 0.38 mg.kg-1, and edrophonium, 0.54 and 1.15 mg.kg-1, respectively. These doses were given by random allocation to the next 60 patients, but at one per cent spontaneous recovery. Neostigmine, 0.04 mg.kg-1, produced a T1 of 73 +/- 4 per cent (mean +/- SEM), and a train-of-four ratio (TOF) of 39 +/- 3 per cent. This was significantly greater than with pyridostigmine, 0.2 mg.kg-1 (T1 = 50 +/- 6 per cent; TOF = 25 +/- 3 per cent), and edrophonium, 0.54 mg.kg-1 (T1 = 54 +/- 3 per cent; TOF = 17 +/- 2 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)     

Phonomyography and mechanomyography can be used interchangeably to measure neuromuscular block at the adductor pollicis muscle

The standard of neuromuscular monitoring is the measurement of the force of contraction (mechanomyography, MMG). Phonomyography (PMG) consists of recording low-frequency sounds created during muscle contraction. In this study, we compared and used both methods to determine neuromuscular blockade (NMB) at the adductor pollicis muscle. In 14 patients, PMG was recorded via a small condenser microphone taped to the thenar mass, and a standard mechanomyographic device was applied to the same arm. In another group of 14 patients, only PMG was measured. After induction of anesthesia, the ulnar nerve was stimulated supramaximally using single twitch stimulation (0.1 Hz) for onset and train-of-four (TOF) stimulation every 12 s during offset of NMB produced by mivacurium 0.1 mg/kg. Onset and recovery indices measured by the 2 methods were compared using Student's t-test (P < 0.05). Similar comparisons were made between the two PMG groups (with or without special board). Agreement between PMG and MMG was examined using a Bland-Altman test. Onset was 165 (68) s versus 172 (67) s [mean (SD)], and maximum blockade was 89 (10)% versus 90 (11)%, for PMG and MMG respectively (NS). Time to 25%, 75%, and 90% recovery was 16.5 (4.2) min, 22.1 (6.9) min, and 24.5 (8.2) min, respectively for PMG, not different from 16.7 (4) min, 22.8 (8.1) min, and 24.8 (8.8) min for MMG. Mean bias was 0% with limits of agreement of -10 and + 10% of twitch height for all signals (MMG minus PMG). Time to TOF of 0.5, 0.7, 0.8, and 0.9, was 1 min faster with PMG than with MMG, with limits of agreement of -1.5 to 3.5 min. Pharmacodynamic data derived without or with special arm fixation were not significantly different. MMG and PMG can be used interchangeably to determine NMB at the adductor pollicis muscle. PMG is easier to apply, does not need a special monitoring board and could be a reliable monitor to determine NMB in daily routine. IMPLICATIONS: Mechanomyography and phonomyography (PMG), a novel method of monitoring neuromuscular blockade (NMB) by recording low-frequency sounds emitted by muscle contraction, can be used interchangeably to determine NMB at the adductor pollicis muscle. PMG is easier to apply, does not need a special monitoring board and could be a reliable monitor to determine NMB in daily routine.     

Dose-response relationships for edrophonium and neostigmine as antagonists of moderate and profound atracurium blockade

To measure the ability of neostigmine and edrophonium to reverse moderate and profound atracurium blockade, dose-response relationships were established for these reversal agents given at 1% and 10% twitch height recovery. Eighty-five ASA I and II adult patients received atracurium, 0.4 mg/kg, during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 seconds, and the force of contraction of the adductor pollicis muscle was recorded. Edrophonium, 0.1, 0.2, 0.4, or 1 mg/kg; neostigmine, 0.005, 0.01, 0.02 or 0.05 mg/kg; or no reversal agent was given when there was either 1% or 10% recovery of the first twitch response. With profound blockade, the slope of the edrophonium dose-response relationship was significantly flatter (P less than 0.05) than that of neostigmine. The dose of neostigmine required to achieve 80% first twitch recovery (ED80) after 10 minutes was 0.013 +/- 0.003 mg/kg (mean +/- SEM) if given at 10% recovery, and 0.032 +/- 0.004 mg/kg if given at 1% recovery. The ED80 for edrophonium was 0.22 +/- 0.04 mg/kg and 1.14 +/- 0.33 mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 16.6 +/- 3.5 and 35.3 +/- 8.9 at 90% and 99% blockade respectively (P less than 0.006). We conclude that the relative potency of neostigmine is greater than that of edrophonium for antagonism of profound atracurium blockade.     

Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia

We determined the dose-response relationships of mivacurium (BW B1090U) in children (2-10 years) during nitrous oxide-halothane anesthesia (0.8% end-tidal) and during nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relationships, for each anesthetic background four subgroups of nine patients received single bolus doses of 20-120 micrograms/kg mivacurium. The ED50 and ED95 (estimated from linear regression plots of log-dose vs. probit of effect) were 52 micrograms/kg and 89 micrograms/kg during halothane anesthesia and 62 micrograms/kg and 103 micrograms/kg during narcotic anesthesia. Nine additional patients in each anesthetic group received 250 micrograms/kg mivacurium. Three of the 18 patients given 250 micrograms/kg mivacurium developed cutaneous flushing; in one of these mean arterial pressure decreased 32% for less than 1 minute; no significant changes in heart rate occurred. With the increase in mivacurium dose from 120 micrograms/kg to 250 micrograms/kg the times to onset of 90% and maximum neuromuscular block decreased by 0.5 to 1 minute, and the times to recovery of neuromuscular transmission to 5% (T5) or 25% (T25) increased by 2-4 minutes. The recovery index (T25-75) in patients anesthetized with halothane was 4.3 +/- 1.5 minute (mean +/- SD); the time to complete recovery (T4:1 greater than or equal to 0.75) was 19.8 +/- 7.4 minutes.