Mivacurium in children with Duchenne muscular dystrophy

The authors retrospectively reviewed their experience with mivacurium for neuromuscular blockade in seven children with Duchenne muscular dystrophy. Mivacurium was administered to seven children ranging in age from 8.3 to 14.4 years and in weight from 29 kg to 68 kg during either posterior spinal fusion or lower extremity release. An initial bolus dose of 0.2 mg·kg^?1 was followed by a continuous infusion. Neuromuscular blockade was monitored with a standard twitch monitor and the TOF (2 Hz for 2 s). Complete suppression of all four twitches occurred in 1.5 to 2.6 min. The continuous infusion was started with the return of the first twitch and adjusted to maintain one twitch. Time to recovery of the first twitch varied from 12 to 18 min. Continuous infusion requirements varied from 3 to 20 μg·kg^?1 with an average for the case of less than 10 μg·kg^?1 min^?1 in five of the seven patients. A moderate increase in sensitivity to mivacurium in this patient population is suggested by a decrease in infusion requirements and a prolonged effect following the initial dose.     

Onset and duration of action of vecuronium in the elderly: comparison with adults

The onset and duration of action of vecuronium were studied in young adult (n = 30; mean age 34 +/- 11.1 (s.d.) yr), middle-aged (n = 20; mean age 60 +/- 5.8 yr) and elderly patients (n = 30; mean age 80 +/- 4.6 yr) anaesthetised with thiopentone, nitrous oxide in oxygen and halothane. Neuromuscular block was monitored by applying the train-of-four (TOF) stimulation at 2 Hz to the ulnar nerve every 12 s. Half the patients in each group received 0.08 and the other half 0.12 mg kg-1 of the relaxant. The time to return of T1 (first response in the TOF sequence) to 25% of control was 28 +/- 5.2 (s.d.), 34 +/- 7.1 and 39 +/- 10.2 min following 0.08 mg kg-1 dose (P less than 0.05 between the elderly and young adults) and 45 +/- 9.2, 48 +/- 6.2 and 69 +/- 19.2 min following 0.12 mg kg-1 dose, respectively, in the three age groups (P less than 0.05 between the elderly and the other two groups). The recovery indices (time for 25-75% recovery of T1) after the 0.08 mg kg-1 was 9.6 +/- 3.4, 13.6 +/- 5.1 and 17.4 +/- 6.1 min, respectively (P less than 0.05 between the elderly and young adults). There was no significant difference in any of the parameters between the young adults and the middle-aged. The onset of block at each dose was not significantly different between the three age groups; however, the time to maximum effect was significantly shorter with the higher dose in the young and the middle-aged, but not in the elderly. Regression analysis of the data between age and the duration of action and recovery index suggested a significant prolongation (P less than 0.05) of these parameters in the elderly.     

Acute quadriplegic myopathy in a 16-month-old child

We present a case of a 16-month old previously healthy child who was hospitalized because of an acute respiratory insufficiency most likely caused by a viral infection and who then developed a severe acute quadriplegic myopathy (AQM). Initial clinical symptoms were respiratory acidosis, dypnea, intense wheezing, and deterioration of the level of consciousness, which required orotracheal intubation and mechanical ventilation. We administered neuromuscular blocking agents, corticosteroids, and antibiotics. After 9 days the clinical picture improved. An attempt to wean from the ventilator failed. We diagnosed AQM. This paper discusses AQM and its clinical importance.     

Rocuronium 0.3 mg x kg-1 (ED95) induces a normal peak effect but an altered time course of neuromuscular block in patients with Duchenne's muscular dystrophy

BACKGROUND: In patients with Duchenne's muscular dystrophy (DMD) recovery from neuromuscular block is delayed. It has been assumed that this is because of a higher potency of muscle relaxants in this patient cohort. We determined the peak effect, and the time course of action of rocuronium 0.3 mg x kg(-1) (ED(95)) in DMD patients. METHODS: Twenty-four patients (12 with DMD and 12 controls; aged 10-18 years) were studied. All patients were anesthetized with propofol and fentanyl/remifentanil. Neuromuscular transmission was monitored by acceleromyography. After induction all patients received a single dose of rocuronium 0.3 mg x kg(-1). The complete time course of action as onset, peak effect and spontaneous recovery was recorded. RESULTS: The onset time (s) to maximum block was significantly (P < 0.01) prolonged in DMD patients (median: 315; range: 120-465) compared with controls (195, 75-270). The peak effect (% twitch depression relative to baseline) was not different between the groups (DMD: 59-100; controls: 28-100). In the DMD group, recovery was significantly (P < 0.01) delayed compared with controls at all recorded time points. The clinical duration (min) was 40.3 (22-89) in the DMD group vs 9.8 (6-17) in the control group (P < 0.01). CONCLUSIONS: The similar peak effect in both groups does not confirm the thesis of rocuronium having a higher potency in DMD patients. The documented very long recovery after the ED(95) of rocuronium emphasizes the need for careful assessment of neuromuscular function in DMD patients.     

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

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

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block

Background. Org 25969 is a cyclodextrin compound designed toreverse a rocuronium-induced neuromuscular block. The aim ofthis study was to explore the efficacy, dose–responserelation and safety of Org 25969 for reversal of a prolongedrocuronium-induced neuromuscular block. Methods. Thirty anaesthetized adult patients received rocuronium0.6 mg kg^–1 as an initial dose followed by incrementsto maintain a deep block at a level of <10 PTCs (post-tetaniccounts) recorded every 6 min. Neuromuscular monitoring was carriedout using accelerometry, in a train-of-four (TOF) mode usingTOF-Watch®SX. At recovery of T₂, following at least 2 hof neuromuscular block, patients received their randomly assigneddose of 0.5, 1.0, 2.0, 4.0 or 6.0 mg kg^–1 of Org 25969.Anaesthesia and neuromuscular monitoring were continued fora minimum period of 30 min after Org 25969 administration. Themain end-point of the study was the time to achieve a sustainedrecovery of TOF ratio to 0.9. Patients were followed up for7 days after anaesthesia. Results. The results showed a dose-related decrease in the averagetime taken to attain a TOF ratio of 0.9 from 6:49 (min:s) withthe 0.5 mg kg^–1 dose to 1:22 with the 4.0 mg kg^–1dose. Weighted non-linear regression analysis showed the fastestachievable time to TOF ratio of 0.9 to be 1:35. Org 25969 producedno major adverse effects. Conclusion. Org 25969 effectively reversed a deep and prolongedneuromuscular block induced by rocuronium. The effective reversaldose appears to be 2–4 mg kg^–1.     

Comparative fading responses induced by mivacurium,cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat

PURPOSE: It has been suggested that the different degrees of fade induced by nondepolarizing neuromuscular blocking agents in repetitive muscular contractions may be due to the varying affinities or binding kinetics of presynaptic nicotinic receptors. We compared the degree of fade induced by mivacurium, cisatracurium, and d-tubocurarine in the cat muscular compound action potential (mCAP). METHODS: In 21 cats, mCAPs of the gastrocnemius muscle were evoked by paired (conditioning and test stimuli) and 2 Hz train-of-four (TOF) sciatic nerve stimulation. The interval between the paired stimuli was changed stepwise from 7 to 1000 ms. The ratios of the amplitude evoked by test stimulus to that evoked by the conditioning stimulus (M2/M1 ratios) and TOF ratios were measured. After baseline variables had been obtained, the cat received either mivacurium (0.08 mg x kg(-1), n = 7), cisatracurium (0.05 mg x kg(-1), n = 7), or d-tubocurarine (0.5 mg x kg(-1), n = 7). A series of M2/M1 ratios and TOF ratios were measured at various levels of partial block during recovery. RESULTS: At 10% of baseline amplitude, all agents significantly depressed the M2/M1 ratios (i.e., fade) at relatively longer intervals of paired stimuli (mivacurium, > or = 100 ms; cisatracurium. > or = 40 ms; and d-tubocurarine, > or = 20 ms), when compared with baseline. The order of activity to produce fade was mivacurium < cisatracurium < d-tubocurarine. A similar result was obtained in TOF ratios measured at various levels of neuromuscular block. CONCLUSION: Our results suggest that mivacurium shows a lesser degree of fade during partial neuromuscular block than cisatracurium and d-tubocurarine.     

A retrospective observational study of neuromuscular monitoring practice in 30,430 cases from six Danish hospitals

Timely application of objective neuromuscular monitoring can avoid residual neuromuscular blockade. We assessed the frequency of objective neuromuscular monitoring with acceleromyography and the last recorded train-of-four ratio in a cohort of Danish patients. We extracted data from all patients receiving general anaesthesia from November 2014 to November 2016 at six hospitals in the Zealand Region of Denmark. Acceleromyography was available in all operating rooms and data were recorded automatically. The primary outcome measure was acceleromyography use in patients receiving neuromuscular blocking agents, divided into non-depolarising agents and succinylcholine only. The dataset included 76,743 cases, of which 30,430 received a neuromuscular blocking drug. Non-depolarising drugs were used in 16,525 (54%) and succinylcholine as the sole drug in 13,905 (46%) cases. Acceleromyography was used in 14,463 (88%) patients who received a non-depolarising neuromuscular blocking drug and in 4224 (30%) receiving succinylcholine alone. Acceleromyography use varied between the departments from 58% to 99% for non-depolarising drugs and from 3% to 79% for succinylcholine alone. The median (IQR [range]) of the last recorded train-of-four ratio before tracheal extubation was 0.97 (0.90–1.06 [0.01–2.20]) when non-depolarising drugs were used, and was less than 0.9 in 22% of cases. The OR for oxygen desaturation was higher with the use of succinylcholine [2.51 (95%CI 2.33–2.70) p < 0.001] and non-depolarising drugs [2.57 (95%CI 2.32–2.84) p < 0.001] as compared with cases where no neuromuscular blockade drug was used. In conclusion, acceleromyography was almost always used in cases where non-depolarising neuromuscular blocking drugs were used, but a train-of-four ratio of 0.9 was not always achieved. Monitoring was used in less than 30% of cases where succinylcholine was the sole drug used.     

The effect of neuromuscular blockade on the efficiency of facemask ventilation in patients difficult to facemask ventilate: a prospective trial

Facemask ventilation of the lungs can be an important rescue intervention in a ‘cannot intubate’ scenario. We assessed the effect of neuromuscular blockade on expiratory tidal volumes in patients with expected difficulty in mask ventilation. The lungs of patients with at least three predictors of difficulty in mask ventilation were ventilated using a facemask held with two hands, with mechanical ventilation set in a pressure‐controlled mode. Tidal volumes were recorded before and after the establishment of complete neuromuscular block. In 113 patients, median (IQR [range]) tidal volume increased from 350 (260–492 [80–850]) ml initially, by 48% to 517 (373–667 [100–1250]) ml 30 s after rocuronium administration, (p < 0.001). After the onset of the complete neuromuscular block, a median tidal volume of 600 (433–750 [250–1303]) ml was observed, corresponding to an increase of 71% from baseline values (p < 0.001), and 16% from values obtained 30 s after rocuronium administration, respectively; p = 0.003). No decrease in the tidal volume during the measurements was observed. We conclude that the administration of rocuronium at a dose of 0.6 mg.kg^?1 was able to improve facemask ventilation in all cases with a potentially clinically relevant increase in tidal volume. The early use of a neuromuscular blocking agent can be considered as a therapeutic option in case of difficulty with mask ventilation.     

Duration of action of an equipotent dose of vecuronium in infants and in children

During general anaesthesia without any volatile anaesthetic agents, ten infants and ten children received incremental doses of vecuronium to achieve a 95% neuromuscular block. Thereafter, the thenar electromyographic response was allowed to recover spontaneously. Total dose of vecuronium to establish a 95.0 ± 0.5% (mean ± SEM) neuromuscular block was 66% greater for children than for infants (73 ± 4 vs. 44 ± 4 μg·kg^?1, P < 0.0001). However, recovery index and time to complete recovery of the neuromuscular function were 88 and 89% longer, respectively, in infants than in children (P < 0.0001). These results of the effect of an equipotent dose of vecuronium in infants and in children confirm that vecuronium is a long acting neuromuscular blocking agent in infants.     

Neuromuscular blocking agents and reversal agents

The neuromuscular junction consists of the motor nerve terminal, the synaptic cleft and post-synaptic nicotinic receptors on the motor end-plate of striated muscle. Neuromuscular blocking drugs are categorized into depolarizing and non-depolarizing agents. They are structurally related to acetylcholine (ACh), containing at least one positively charged quaternary ammonium radical that binds to the nicotinic receptor. Depolarizing agents (e.g. suxamethonium) act as agonists like ACh at the nicotinic receptor, but cause a more prolonged depolarization of the motor end-plate, thus rendering the ion channel insensitive to further action potentials. Non-depolarizing agents, in contrast, compete directly with ACh for nicotinic receptor binding sites and prevent neurotransmitter–receptor binding. These are either benzylisoquinoliniums (e.g. atracurium) or aminosteroids (e.g. rocuronium). Once recovery has commenced, neuromuscular block can be reversed with anticholinesterases (e.g. neostigmine). In contrast, the novel cyclodextrin sugammadex can be used to reverse any degree of neuromuscular block produced by rocuronium or vecuronium.     

Response to double-burst appears before response to train-of-four stimulation during recovery from non-depolarizing neuromuscular blockade

Background: Double-burst stimulation (DBS) it a relatively new nerve stimulation mode introduced for improved manual detection of residual neuromuscular blockade. Previous studies have shown that DBS_{3,3 50/50} (3 stimuli at 50 Hz followed 0.75 seconds later by 3 stimuli at 50 Hz) can detect deeper degrees of neuromuscular blockade than train-of-four (TOF) stimulation.
Aim: The aim of the present study was to examine if DBS_{3,3 80/40} (3 stimuli at 80 Hz followed 0.750 s later by 3 stimuli at 40 Hz) can detect even deeper degrees of neuromuscular blockade than DBS_{3,3 50/50} and to determine the time lapse from reappearance of response to each of the two DBS modes until reappearance of response to the TOF mode of nerve stimulation.
Methods: The study comprised 20 women undergoing gynaecological surgery and anaesthetised with fentanyl, thiopentone, halothane, and nitrous oxide. Neuromuscular transmission was monitored by using mechanomyography and stimulation of the ulnar nerve. Atracurium was used for neuromuscular blockade.
Results: Elapsed time from reappearance of response to DBS_{3,3 80/40} and DBS_{3,3 50/50} to reappearance of response to TOF stimulation was 459±196 (mean±SD) and 360±150 seconds, respectively, ( P <0.05).
Conclusions: DBS_{3,3 80/40} is capable of detecting deeper degrees of blockade than DBS_{3,3 50/50} which again is capable of detecting deeper degrees of blockade than TOF.     

Neuromuscular blocking agents and reversal agents

The neuromuscular junction consists of the motor nerve terminal, the synaptic cleft and post-synaptic nicotinic receptors on the motor end-plate of striated muscle. Neuromuscular blocking drugs are categorized into depolarizing and non-depolarizing agents. They are structurally related to acetylcholine (ACh), containing at least one positively charged quaternary ammonium radical that binds to the nicotinic receptor. Depolarizing agents (e.g. suxamethonium) act as agonists like ACh at the nicotinic receptor, but cause a more prolonged depolarization of the motor end-plate, thus rendering the ion channel insensitive to further action potentials. Non-depolarizing agents, in contrast, compete directly with ACh for nicotinic receptor binding sites and prevent neurotransmitter–receptor binding. These are either benzylisoquinoliniums (e.g. atracurium) or aminosteroids (e.g. rocuronium). Once recovery has commenced, neuromuscular block can be reversed with anticholinesterases (e.g. neostigmine). In contrast, the novel cyclodextrin sugammadex can be used to reverse any degree of neuromuscular block produced by rocuronium or vecuronium.     

Comparison of thumb acceleration and thenar EMG in a pharmacodynamic study of alcuronium

We compared thumb acceleration (Acc) and thenar electromyography (EMG) techniques by evaluating the neuromuscular blocking properties of alcuronium in 14 ASA physical status I patients. The dose-response curves determined by the two techniques were parallel but the EMG-curve was shifted 25% to the right (P less than 0.001). Acc reflected 8-11% greater neuromuscular block than simultaneous EMG in every patients (P less than 0.05). Concurrently, the duration of greater than 90% neuromuscular block maintained by alcuronium 280 micrograms/kg was significantly longer when measured by the Acc transducer (30 vs. 19 min, P less than 0.001). Although the TOF ratios were in good correlation (r2 = 0.82), clinically significant differences existed between the two simultaneous techniques. The results underline the importance of the method of assessment of neuromuscular transmission when evaluating the action of neuromuscular blocking drugs.     

A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anaesthesia along with propofol

Background: Rocuronium has an onset of action more rapid than other non-depolarizing neuromuscular blocking agents, but it is unclear whether it and succinylcholine give equivalent intubating conditions during rapid-sequence induction of anaesthesia. We performed this study to answer the question – are there clinically relevant differences between the use of rocuronium and succinylcholine to secure acceptable intubating conditions during rapid-sequence induction of anaesthesia with propofol? Methods: Anaesthesia was induced using propofol 2.5 mg/kg in 349 ASA physical status grade I–IV patients who were undergoing either elective or emergency surgery. Propofol was followed immediately by either rocuronium 0.6 or 1 mg/kg or succinylcholine 1.0 mg/kg (randomly selected). Fifty seconds after the end of muscle relaxant injection laryngoscopy was performed and intubating conditions were graded by an experienced anaesthetist blind to the muscle relaxant allocation. This study design was selected so that a 10% difference in clinically acceptable intubating conditions between drugs would be detectable. Results: In this setting rocuronium 1.0 mg/kg provided superior intubating conditions compared with rocuronium 0.6 mg/kg. The incidence of clinically acceptable intubating conditions with rocuronium 1.0 mg/kg and succinylcholine 1.0 mg/kg was 93.2% and 97.1% respectively, the difference being ?3.9% (95% C.I. ?9.7% to 1.9%). Conclusion: Rocuronium 1.0 mg/kg given along with propofol in a rapid-sequence induction of anaesthesia is clinically equivalent to succinylcholine 1.0 mg/kg.     

Intubating conditions and onset of neuromuscular block of rocuronium (Org 9426); a comparison with suxamethonium

The intubating conditions and neuromuscular blocking profile following 600 micrograms.kg-1 rocuronium (Org 9426) have been investigated in patients under various experimental conditions. They were compared with conditions following 1.5 mg.kg-1 suxamethonium, preceded by a precurarising dose (10 mg) of gallamine, and with those in a control group in the absence of a muscle relaxant. Rocuronium produced good to excellent intubating conditions at 60 as well as at 90 s after administration, even though there was only a partial blockade of the adductor pollicis muscle. Intubating conditions following suxamethonium were comparable with those after rocuronium. Half of the control patients could be intubated. The clinical duration and the recovery time of 600 micrograms.kg-1 of rocuronium were 24(4) and 9(3) min (mean(s.d.)), respectively. Rocuronium may have a major advantage over existing non-depolarising muscle relaxants due to the early presence of excellent intubating conditions. The results indicate that rocuronium may replace suxamethonium in procedures in which rapid sequence induction is required.     

术后非去极化肌松药肌松残余拮抗新进展

背景非去极化肌松药在临床麻醉中使用非常普遍,术后不可避免地发生肌松残余作用,其危害主要为呼吸不良事件,严重可导致死亡。 目的有效合理的肌松拮抗能降低术后肌松残余的发生率,减少相关并发症,因此,拮抗至关重要。内容阐述非去极化肌松药使用后手术结束时是否需要拮抗、拮抗的时机、拮抗剂的剂量和新的拮抗模式。趋向选择性肌松拮抗可...     

残余肌松与全麻术后呼吸功能不全关系的临床研究

目的 了解全麻手术后在麻醉恢复室(postanesthesia care unit,PACU)内呼吸功能不全的发生率,并评估其与残余肌松的关系.方法 择期全麻手术成年患者623例,术后PACU内用4个成串刺激(TOF)监测肌松,按临床指征拔管,根据拔管后即刻测量TOF值将患者分成3组,TOF＞0.9为A组；TOF 0.7～0.9为B组；TOF＜0.7为C组,记录每组出现呼吸功能不全的例数.结果 全麻手术后在PACU内呼吸功能不全的发生率为4.5％,A组患者472例,其中有7例(1.5％)出现呼吸功能不全,B组患者112例,9例(8.0％)出现,C组患者39例,有12例(30.8％)出现,最常见的是低氧血症和上呼吸道梗阻.C组与A组和B组比较及B组与A组比较,出现呼吸功能不全比例明显增高(P＜0.01).结论 存在残余肌松(TOF＜0.9)的患者更易出现术后呼吸功能不全,应加强围手术期肌松监测,掌握恰当的拔管时机.