Neuromuscular effects of 600 μg·kg−1 of rocuronium in infants during nitrous oxide-halothane anaesthesia

Rocuronium bromide (Zemuron) is a new steroidal nondepolarizing neuromuscular blocking drug. We were interested in determining the effect of a bolus of rocuronium in infants during halothane anaesthesia as we did previously in older children. Eighteen infants (2-11 months) received a bolus of 600 μg·kg^?1, which is equal to twice the dose of rocuronium estimated to produce 95% depression of neuromuscular function (ED₉₅) in children (2-12 yr). Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Time (mean ± SEM, range) from administration of 600 μg·kg^?1 rocuronium to 90% (B₉₀) and 100% (B₁₀₀) neuromuscular block was 37 ± 2 (20-60) s and 64 ± 10 (20-180) s, respectively. The time to recovery of neuromuscular transmission to 10% (T₁₀) was 35.3 ± 3.0 (20.7-57.8) min and to 25% of baseline (T₂₅) was 41.9 ± 3.2 (24.3-67.7) min. The recovery index (T₂₅-T₇₅) was 26.6 ± 2.7 (11.7-44.5) min, and the time to recovery of the train-of-four ratio (T₄/T₁) ± 0.75 was 82.1 ± 6.9 (53.2-138.3) min. The plasma concentration of rocuronium when T₁ had recovered to about 30% was 654 ± 34 (417-852) ng·ml^?1 which is similar to that observed in children. Six-hundred μg·kg^?1 of rocuronium has a rapid onset of effect in infants and prolonged duration of action in infants compared to children.     

Oral clonidine does not alter vecuronium neuromuscular blockade in anaesthetized patients

Since clonidine, an α₂-agonist, inhibits the release of norepinephrine or acetylcholine which can decrease nondepolarizing muscle relaxant-induced neuromuscular blockade, the authors examined whether clonidine given as an oral preanaesthetic medication would alter the onset, duration or recovery of a vecuronium neuromuscular blockade in lightly anaesthetized patients. Thirty-eight patients (aged 20–73 yr) randomly received oral clonidine either approximately 5 μg · kg^?1 (n = 21) or none (n = 17), 90 min before arrival in the operating room. We measured acceleration of thumb contraction with ulnar nerve stimulation at the wrist to assess neuromuscular blockade. The onset time (the time from injection to decrease to 5% of baseline twitch height), duration (the time interval between injection and return of the first twitch to 25% of the baseline value), and recovery index (the time interval of the first twitch from 25% to 75% of the baseline value) of neuromuscular blockade from a single bolus of vecuronium 0.1 mg · kg^?1 iv were determined and compared between the clonidine-treated and control patients during lower abdominal or extremity surgery under epidural plus general anaesthesia with fentanyl and nitrous oxide in oxygen. No differences were noted between the control and clonidine groups in onset time (100 ± 6 sec (mean ± SE) vs 101 ± 6 sec), duration (44.5 ±2.7 min vs 42.9 ±2.7 min), or recovery index (21.6 ± 2.8 min vs 19.1 ± 1.9 min) of neuromuscular blockade from vecuronium, respectively. These results show that oral preanaesthetic medication of clonidine 5 μg · kg^?1 does not alter neuromuscular blockade induced with vecuronium 0.1 mg · kg^?1 in patients during combined epidural and fentanyl/nitrous oxide general anaesthesia.     

Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans andtrans-trans) undergo rapid metabolism by plasma cholinesterase (t_1/2 β<2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5– 10% of control T₁ amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg · kg^{? 1} (Group EDR- 1), 0.25 mg · kg^{? 1} (Group EDR- 2), or 0.50 mg · kg^{? 1} (Group EDR- 3), in addition to a corresponding dose of atropine. 4Spontaneous recovery, from a T₁ response of<10% to a TOF ratio ≥0.7, required 13.5 ± 2.6 min (PLAC Group). In comparison, patients in the EDR- 1 group required 9.2 ± 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of ≥ 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an E^UE^A genotype, whereas the two patients with delayed recovery in the EDR- 1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg · kg^{? 1}) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg · kg^{? 1} provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.     

Neuromuskuläre Blockade mit Atracurium bei Dermatomyositis

Dermatomyositis (DM) is a rare disease of unknown aetiology involving weakness of proximal muscles, myalgia and impairment of the integument. Due to its low incidence, only few reports exist on the anaesthesiologic management of neuromuscular blockade in patients with DM considered for surgical therapy. In this setting, special attention should be given to the administration of muscle relaxants since an increased sensitivity to these drugs in neuromuscular diseases may be expected. Methods. This case report describes the neuromuscular monitoring of a female patient aged 53 years with DM undergoing strumectomy and treated with methotrexate and prednylidene. Muscle relaxation was induced with 0.35?mg/kg atracurium (1.5×ED₉₅). An additional bolus of 0.07?mg/kg was administered 50?min later. Control of sufficient relaxation was performed by tactile methods, and time of onset (TO), duration of action (DA) and recovery index (RI) were measured. Results. Relaxation was obtained within TO of 3?min, DA of 50?min and RI of 11?min. These timer indicate slightly increased sensitivity to atracurium. The postoperative outcome demonstrated no muscular weakness and sufficient spontaneous ventilation. Discussion. To date, few experiences of neuromuscular blockade with atracurium in DM have been presented, hence this report. In addition, no standard recommendations are given regarding the application of nondepolarizing muscle relaxants in this context. In our case, atracurium could be implemented as a safe drug under neuromuscular monitoring.     

The reversal of profound mivacurium-induced neuromuscular blockade

Purpose

Mivacurium is metabolized by plasma cholinesterase catalyzed ester hydrolysis. Acetylcholinesterase antagonists used in the reversal of muscle relaxation may also inhibit plasma cholinesterase and, therefore, delay the hydrolysis of mivacurium. The clinical interaction between acetylcholinesterase antagonists and mivacurium induced neuromuscular blockade was studied.

Method

Intraoperative muscle relaxation was maintained with a mivacurium infusion to achieve a constant intense block (first twitch, T¹, 2–3% of control). Patients were randomly divided into three groups. Patients in Group 1 received no anticholinesterase, in Group 2 neostigmine 0.07 mg · kg^?1, and in Group 3 edrophonium 1 mg · kg^?1. The times between termination of the mivacurium infusion (Group 1) or the administration of the anticholinesterase (Groups 2 and 3) to 25%, 50%, 75% and 95% T₁ recovery, and to 50%, 70% and 90% recovery in the ratio, T₄/T₁ (TR) were recorded.

Result

In the neostigmine Group, T₁ recovery to 25%, 50% and 75% ( 2.32 ± 1.41, 3.90 ± 1.85 and 6.88 ± 2.66 min) was accelerated compared with control (3.36 ± 1.34, 5.78 ± 2.22, and 8.58 ± 3.60, and), but recovery to 95% (18.53 ± 9.09 vs 13.29 ± 5.24 min) was delayed. Also, TR recovery to 50%, 70%, and 90% was slower (14.47 ± 8.73, 21.25 ± 11.06 and 31.37 ± 12.11 min vs 11.75 ± 3.74, 13.78 ± 4.39 and 17.86 ± 6.44 min). However, all T₁ and TR recovery times were decreased in the edrophonium group (0.88 ± 0.51, 2.00 ± 1.50, 4.97 ± 2.96, and 9.35 ± 5.24 min for T₁ and 6.86 ± 3.93, 9.05 ± 4.51 and 12.24 ± 6.66 min for TR).

Conclusion

Neostigmine reversal of intense mivacurium neuromuscular block should be avoided, as this may result in prolongation of the block.     

Mivacurium in infants and children

Mivacurium is the only available short-acting nondepolarizing muscle relaxant in clinical use. It is a bis-quaternary benzylisoquinolinium ester hydrolysed by plasma-cholinesterase into inactive compounds. The ED₅₀ and ED₉₅ in children are about 50 μg·kg^?1 and 90 μg·kg^?1 respectively. In infants, they have a tendency to be lower. A standard intubating dose of 0.25 mg·kg^?1 causes complete neuromuscular depression in 1.5–2 min, recovery to 5% in 6–10 min, and complete recovery in 15–20 min. The recent tendency is to use 0.3 mg·kg^?1 to obtain better intubating conditions with slight prolongation of effect. Since the recovery profile of mivacurium is independent of the dose and duration, it is most suitable for administration by continuous infusion. The infusion requirement in children is 10–16 μg·kg^?1 min^?1, which is about twice that of adults. Cutaneous flushes from histamine release are commonly seen with the larger doses of mivacurium; however, the associated hypotensive effects are minimal and counteracted by the tracheal intubation. The duration of action of mivacurium is prolonged in patients with cholinesterase deficiency. Mivacurium's neuromuscular effects can be satisfactorily antagonized by edrophonium or neostigmine.     

Total intravenous anesthesia without muscle relaxant in a patient with amyotrophic lateral sclerosis

A 63-year-old woman with amyotrophic lateral sclerosis (ALS) was scheduled for open reduction and internal fixation of the right tibia. Total intravenous anesthesia using propofol and remifentanil without muscle relaxant was selected as the anesthetic method, in order to avoid the possible occurrence of ventilatory depression due to abnormal responses to muscle relaxants and exacerbation of the motor neuron disease. After standard and neuromuscular monitoring devices were applied, anesthesia was induced and maintained with target controlled infusion of propofol and remifentanil in the range of 2.5–5.0 μg·ml⁻¹ and 2.5–5.0 ng·ml⁻¹, respectively. To avoid delayed neuromuscular recovery, we did not use any muscle relaxant at all. Intubation was successful and there were no remarkable events during anesthesia, except for three brief hypotensive events; there was no exacerbation of ALS itself during or after the anesthesia. She was discharged on postoperative day 3, without any discomfort.     

Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

Purpose

To determine the characteristics of neuromuscular block produced by two and three times the 95% effective dose (ED₉₅) of doxacurium in patients undergoing coronary artery surgery with hypothermic cardiopulmonary bypass.

Methods

In a prospective non randomized study, ten patients received doxacurium 0.05 mg·kg^?1 (Group 1) and ten others received 0.075 mg · kg^?1 (Group 2) with midazolam and sufentanil. The mechanomyographic response of the adductor pollicis muscle after supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium (10% of the initial dose) was administered until sternal closure whenever the first twitch (T₁) had recovered to 25% of control.

Results

The onset time (time to maximal T₁ depression) of doxacurium was 390 ± 148 sec in Group 1 and 370 ± 74 sec in Group 2 (P = 0.71). The clinical duration of neuromuscular block (time to 25% T₁ recovery) was 165 ± 90 min in Group 1 and 258 ± 86 min in Group 2 (P = 0.03). On arrival to recovery room the mean T₁ was 57 ± 23% in Group 1 and 24 ± 21% in Group 2(P = 0.003); the mean T₄/T₁ ratio was 0.25 ± 0.15 for five patients of Group 1 with four responses to TOF stimulation and 0.10 for the only patient of Group 2 with four twitches.

Conclusion

In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED₉₅. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.     

Pharmacodynamic behaviour of rocuronium in the elderly

This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I– II patients (60, âgéd 65–80 yr, and 40, âgéd 20–45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N₂O/O₂ and fentanyl, rocuronium 120,160, 200, or 240 μg · kg ^?1 was administered to determine dose-response curves. When maximum block had been obtained,further rocuronium to a total of 300 μg · kg ^?1 was given. Additional doses of 100 μg · kg^?1 were administered when the first twitch height (T₁) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T₁ was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED₅₀ was 196 ±8 (SEE for the mean) in elderly,vs 215 ±17 iμg · kg ^{? 1} in young patients (NS). When individual cumulative dose-response curves were constructed, the ED₅₀ was 203 ± 7(SEM) and 201 ± 10 μg · kg ^{? 1} in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 ±1.1 (SD) vs 3.1 ± 0.9 min, P < 0.05). The time to 25% T ₁ recovery was longer in the elderly (11.8 ± 8.1 vs 8.0 ± 6.5 min,P <0.05) as was the recovery index, time from 25 to 75% T₁ recovery (15.5 ± 6.2 vs 11.2 ± 4.9 min, P< 0.05). The duration of neuromuscular block after each maintenance dose was longer in the elderly (P <0.01) and increased gradually with time. It is concluded that rocuronium is an intermediate-acting neuromuscular blocking drug with a similar potency in elderly and young patients, but the onset and recovery of neuromuscular blockade are slower in the elderly.     

Drugs to facilitate recovery of neuromuscular blockade and muscle strength

Several drugs that quicken recovery from neuromuscular blockade caused by vecuronium in anesthetized patients are reviewed. Ulinastatin, a protease inhibitor, is thought to promote the release of acetylcholine at the neuromuscular junction and increases hepatic blood flow and urine volume. For this reason, ulinastatin quickens recovery from neuromuscular blockade in anesthetized patients receiving vecuronium. Additionally, pretreatment with ulinastatin avoids prolongation of vecuronium-induced neuromuscular blockade in patients with hepatic cirrhosis. Gabexate mesilate is also a protease inhibitor. During a continuous infusion of gabexate mesilate, recovery from neuromuscular blockade was quickened. Amino acid-enriched solution supplies energy to the skeletal muscles and causes an increase in muscle strength. An infusion of amino acid-enriched solution hastens recovery from neuromuscular blockade in anesthetized patients. When amino acids supply energy to the skeletal muscles, they simultaneously produce heat in the skeletal muscles. This thermal generation may be closely related to fast recovery from neuromuscular blockade. Amino acid-enriched solution makes recovery from neuromuscular blockade quick and avoids hypothermia during general anesthesia. Milrinone, a phosphodiesterase III inhibitor, is supposed to increase the release of acetylcholine at the neuromuscular junction and make the neuromuscular junction sensitive to acetylcholine. Therefore, recovery from neuromuscular blockade is hastened. Nicorandil enhances membrane K⁺ conductance in skeletal muscle and increases contraction of the skeletal muscle. Thus, nicorandil quickens recovery from neuromuscular blockade.     

Variability of pipecuronium neuromuscular blockade

The dose-response relationship and the variability of the time variables in pipecuronium neuromuscular blockade were studied in 29 patients (ASA physical status 3) during halothane anaesthesia. The ED₉₅ (twitch tension) was determined in 9 patients using the cumulative dose response technique. Another 20 patients received the resulting ED₉₅ as a single bolus. The mean ED₉₅ was 35 μg-kg^-1 (95% confidence interval: 29–41 μg.kg^-1). Following bolus injection of 1. ED₉₅, an 80–100% twitch depression was achieved within 4.6±1.3 min (mean ± s.d.). The duration from end of injection of pipecuronium to 25% twitch recovery, the time from 25% to 75% twitch recovery, and the time from 25% twitch recovery to the train-of-four ratio (TOF) returning to 0.7 was 35 ± 14, 37 ± 26, and 63 ± 27 min, respectively. The time from end of injection to TOF = 0.7 varied within a 2-h range (54–160 min). Thus, the time variables in pipecuronium neuromuscular blockade were as poorly predictable as those reported in the literature on pancuronium, alcuronium and doxacurium.     

Recovery of neuromuscular function after atracurium and pancuronium maintenance of pancuronium block

The study was undertaken to determine whether a neuromuscular blockade induced with pancuronium but maintained with atracurium was associated with a shorter time to complete recovery after administration of neostigmine than if the blockade was maintained with pancuronium alone. Anaesthesia consisted of thiopentone, N₂O/O₂/enflurane and fentanyl, and the neuromuscular blockade, induced by pancuronium 0.1 mg · kg^?1 was monitored by the force of contraction of adductor pollicis during major abdominal surgery lasting 2–5 hr. In 24 patients — Group 1 — atracurium 0.07 mg · kg^?1 was repeated when the first twitch of the train-of-four (TOF) returned to 25% of control (T₁/ TC 25). In 28 patients — Group 2 — pancuronium 0.015 mg · kg^?1 was given at similar recovery of T₁/ TC. At the end of surgery, neostigmine 0.07 mg · kg^?1 and glycopyrrolate 0.015 mg · kg^?1 were given to reverse the residual neuromuscular blockade which was indicated by a T₁/TC of less than 25% in all patients. The time from injection of the reversal drugs to a TOF ratio of 70% was similar in both groups (Group 1, 11.6 ± 7.6 min; Group 2, 10.1 ± 6 min; P = NS), but the recovery index was smaller in Group 2 (Group 1, 4 ± 2.6 min; Group 2, 2.61 ± 1.2 min; P < 0.05). Furthermore, there was no difference between groups in the duration of action of each redose. The study showed that when compared with pancuronium, equipotent doses of atracurium were not associated with (a) a shorter time to complete recovery from a neuromuscular blockade induced with pancuronium or (b) a shorter duration of action.     

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.     

Rocuronium in infants, children and adults during balanced anaesthesia

We studied 20 infants, 20 children and 20 adults during balanced anaesthesia to compare the neuromuscular blocking effects of rocuronium in these age groups. Neuromuscular function was recorded by adductor pollicis emg and a cumulative log-probit dose-response curve of rocuronium was established. Thereafter, full spontaneous recovery of the neuromuscular function was recorded. Onset time of the first dose of rocuronium was shorter in children than in infants or adults. The potency of rocuronium was greatest in infants and least in children; the ED₅₀ doses (mean ± SD) being 149 ± 36 μg˙kg^?1 in infants, 205 ± 52 μg˙kg^?1 in children and 169 ± 47 μg˙kg^?1 in adults (P<0.05 between infants and children) and the ED₉₅ doses being 251 ± 73 μg˙kg^?1, 409 ± 71 μg˙kg^?1 and 350 ± 77 μg˙kg^?1, respectively (P<0.05 between all groups). The emg recovery following an average 94.5 ± 4.8% neuromuscular blockade established by rocuronium was roughly similar in all study groups. Thus, one ED₉₅ dose of rocuronium, unlike vecuronium, acts as an intermediate-acting agent in all age groups.     

Recovery of train-of-four after mivacurium

The present study was designed to determine the time-course of recovery of the train-of-four (TOF) ratio during spontaneous recovery from mivacurium-induced block. Fifteen patients, free of neuromuscular disease, undergoing general endotracheal anaesthesia with isoflurane were studied. After anaesthetic induction, patients received a bolus dose of mivacurium 0.15 mg · kg^?1. The TOF was then recorded continuously every 12 sec with a mechanogram (adductor pollicis monitor). When the TOF ratio recovered spontaneously to 0.9, an additional 0.05 mg · kg^?1 of mivacurium was given. The durations required for recovery from a TOF ratio of 0.3 to 0.7 (DUR_0.3–0.7) and from a TOF ratio of 0.3 to 0.9 (DUR_0.3–0.9) were determined. The DUR_0.3–0.7 averaged 7.0 ± 2.5 min (range 3.4–12.2 min). The DUR_0.3–0.9 averaged 11.8 ± 3.9 min (range 6.0–20.2 min). There was no evidence of prolongation of recovery times (cumulation) following repeated dosing. The present data indicate that, in patients with normal cholinesterase activity (clinical duration 7–25 min), waiting 20 min beyond the time when fade is no longer apparent by visual or tactile evaluation is sufficient to attain a TOF ratio greater than 0.7–0.9 during spontaneous recovery from mivacurium, and may enable anaesthetists to avoid antagonism of mivacurium-induced block.     

Clinical use of atracurium in my asthenia gravis a case report

A patient with myasthenia gravis was anaesthetized for thymectomy utilizing atracurium for maintenance of muscle relaxation. The patient was not taking anticholin-esterase medications before surgery. Neuromuscular function was monitored by recording the train-of-four response to supramaximal stimulation of the ulnar nerve. Anaesthesia was induced with thiopentone and maintained with isoflurane and N₂O in oxygen. Following complete recovery from a succinylcholine block for intubation, the patient developed complete neuromuscular block within two minutes after atracurium (5 mg) was administered. Evidence of recovery commenced 12 minutes later and was complete at 72 minutes. This rate of recovery is consistent with the recovery rate from atracurium during isoflurane anaesthesia in normal patients. Atracurium appears to offer an advantage over other nondepolarizing muscle relaxants in patients with myasthenia gravis due to its shorter duration and less cumulative effect at the neuromuscular junction.     

Monitoring of neuromuscular blockade in one muscle group alone may not reflect recovery of total muscle function in patients with ocular myasthenia gravis

Purpose

We report on two patients with ocular myasthenia gravis who received rocuronium, followed later by sugammadex to reverse neuromuscular blockade. Recovery was monitored simultaneously at the adductor pollicis muscle (APM) and the corrugator supercilii muscle (CSM).

Clinical features

Two patients with ocular myasthenia gravis (case 1: 74 yr-old female, 54 kg; case 2: 71 yr-old male, 72 kg) were scheduled for surgery under general anesthesia. Neuromuscular blockade was induced with rocuronium 0.3 mg·kg^?1 after placing two separate monitors at the APM and the CSM, respectively. Additional doses of rocuronium 0.1-0.2 mg·kg^?1 were given to maintain neuromuscular blockade at fewer than two twitches at the APM during surgery. Train-of-four response at the CSM did not show recovery of the twitch after its initial disappearance. At the end of surgery, sugammadex was administered. Twitch height at the APM recovered to the control value in 12 min (case 1) and 13 min (case 2) after sugammadex administration; however, twitch height at the CSM took 26 min (case 1) and 14 min (case 2) to recover to the control value.

Conclusion

After rocuronium-induced paralysis in both patients with ocular myasthenia, spontaneous recovery and sugammadex-assisted recovery were slower at the CSM than at the APM. In patients without the disorder, CSM recovery is faster than APM recovery. Thus, in ocular myasthenia gravis, neuromuscular recovery at the APM may not reflect recovery of all muscles.     

Recovery of neuromuscular blockade caused by vecuronium is delayed in patients with hypertriglyceridemia

We investigated the effects of hypertriglyceridemia on the onset and recovery of neuromuscular blockade, induced by vecuronium, over the adductor pollicis muscle, electromyographically. Eighteen adult patients with hypertriglyceridemia (hypertriglyceridemia group) and 18 healthy patients with normal serum triglyceride (control group) were studied. The supramaximal stimulating current for train-of-four (TOF) in the hypertriglyceridemia group was significantly higher than that in the control group (45.7 ± 16.7 vs 31.5 ± 9.8 mA; mean ± SD; P = 0.004). The onset of vecuronium 0.1 mg·kg⁻¹-induced neuromuscular blockade in the hypertriglyceridemia group did not significantly differ from that in the control group (240 ± 60 vs 279 ± 88 s; P = 0.132). Times from vecuronium to the return of T1, T2, T3, and T4 in the hypertriglyceridemia group were significantly longer than those in the control group (31.4 ± 6.2 vs 25.5 ± 6.2 min for T1; P = 0.008). During recovery from neuromuscular blockade, T1/control did not differ between the two groups. However, the TOF ratios (T4/T1) in the hypertriglyceridemia group were significantly lower than those in the control group 80–120 min after vecuronium (P < 0.05). We conclude that, in patients with hypertriglycemidemia, a higher current is needed to elicit supramaximal response of the adductor pollicis muscle, and recovery from vecuronium-induced neuromuscular blockade is delayed.     

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.     

Surgeon-controlled mivacurium administration during elective Caesarean section

We have compared the dose requirements and recovery characteristics of a continuous mivacurium infusion given by the anaesthetist to maintain 95–100% block at the hand muscles with that of a surgeon-controlled, on-demand dosing technique based on the direct assessment of abdominal muscle tone during elective Caesarean section. Twenty-four full term pregnant patients were included. A rapid-sequence induction using thiopentone 3–5 mg· kg^?1 and succinylcholine 1 mg· kg^?1 was used. Anaesthesia was maintained with fentanyl, N₂O and iso-flurane 0.5%. The mechanomyographic response of the adductor pollicis muscle to supramaximal train-of-four (TOF) ulnar nerve stimulation was recorded. Muscle relaxation was achieved initially with mivacurium 0.1 mg· kg^?1 followed either by a continuous infusion of mivacurium to maintain 95–100% block at the adductor pollicis muscle (n = 12) or by surgeon-controlled relaxation (SCR) technique using a syringe pump for patient-controlled analgesia to administer on-demand doses of mivacurium 0.05 mg · kg^?1 (n = 12). The lockout interval was three minutes and the maximum hourly dose of mivacurium allowed was 0.6 mg · kg^?1. The total doses of mivacurium (mean ±SD) were 23.2 ± 10.4 and 12.4 ± 3.5 mg in the infusion and SCR groups, P < 0.01. On-demand, surgeon-controlled doses of mivacurium were injected at a mean of T₁ 42.3 ± 36%. At the end of surgery, T₁ and TOF ratio were respectively 16.7 ± 13%, 5 ± 10% and 48 ± 37%, 30 ± 24% in the infusion and SCR groups. Five patients in the SCR group and one patient in the infusion group did not receive antagonist at the end of surgery. The time to adequate recovery, TOF 75%, after skin closure was 8.2 ± 2.3 and 5.3 ± 4 min in the infusion and SCR groups, P = 0.05. It is concluded that, compared with a continuous mivacurium infusion, the SCR technique is associated with reduced mivacurium requirements, a substantial degree of neuromuscular recovery at the end of surgery and a reduced need for neostigmine reversal in full term pregnant patients undergoing elective Caesarean section.