七氟醚对非去极化肌松药与肌肉型乙酰胆碱受体作用的影响

目的探讨七氟醚增强非去极化肌松药肌松作用的机制。方法从大鼠肌肉提取多聚腺嘌呤mRNA,注入去膜的非洲爪蟾卵母细胞以表达有功能的离子通道,利用电压钳技术记录电压依赖性的离子通道电流。建立七氟醚、罗库溴铵和维库溴铵分别抑制乙酰胆碱所引起电流的量效曲线,再研究给予相当于50%抑制率浓度的七氟醚后,罗库溴铵和维库溴铵抑制作用的变化。结果七氟醚、罗库溴铵和维库溴铵均能产生快速、稳定、可逆、浓度依赖性的抑制。达到50%抑制率的浓度分别是823μmol.L-1(95%C I:681~997μmol.L-1)、33.4 nmol.L-1(95%CI:27.1~41.7nmol.L-1)和9.2 nmol.L-1(95%CI:7.9~12.3 nmol.L-1)。联合使用七氟醚、非去极化肌松药时,七氟醚增强非去极化肌松药的抑制效应。结论七氟醚增强非去极化肌松药肌松作用的机制可能是在受体水平增加拮抗剂的亲和力。     

The effect of intravenous paracetamol for the prevention of rocuronium injection pain

Rocuronium is a nondepolarizing neuromuscular blocking agent used in anesthesia induction and is associated with considerable discomfort and burning pain during injection, which is reported to occur in 50–80% of patients. This study was carried out to investigate the effectiveness of intravenous paracetamol pretreatment compared with lidocaine and normal saline to prevent rocuronium injection pain. The study included 150 ASA I–II patients undergoing elective orthopedic, gastrointestinal, and gynecological procedures under general anesthesia. They were allocated into three groups according to pretreatment drugs: lidocaine (40 mg) (n = 50), paracetamol (n = 50), and normal saline group (n = 50). Before anesthesia induction with propofol, all patients were pretreated with rocuronium. The pain caused by the injection was evaluated. Local signs were assessed on the arm at the end of the injection, as well as 24 hours after recovery from anesthesia. There were no patients with blurred speech or vision and there was no respiratory depression in any group after pretreatment with the study drug. The level of pain on injection was statistically lower in those who had received paracetamol compared to normal saline (p = 0.009). There were more patients in the saline group with severe pain (p < 0.001). Paracetamol relieved the rocuronium injection pain better than normal saline but lidocaine was the best of the three drugs (p < 0.001).     

Effects of pretreatment with cisatracurium, rocuronium, and d-tubocurarine on succinylcholine-induced fasciculations and myalgia: a comparison with placebo

Study Objective: To evaluate the efficacy of cisatracurium, rocuronium, and d-tubocurarine in preventing succinylcholine-induced fasciculations and postoperative myalgia in patients undergoing ambulatory surgery.

Design: Randomized, prospective, placebo-controlled trial

Setting: Teaching hospital.

Subjects: 80 ASA physical status I and II patients scheduled for elective ambulatory surgery with general anesthesia.

Intervention: A standardized balanced anesthetic technique was used for all patients.

Measurements and Main Results: Patients were randomized to receive cisatracurium 0.01 mg/kg, rocuronium 0.06 mg/kg, d-tubocurarine 0.05 mg/kg, or saline, 3 minutes prior to intravenous (IV) succinylcholine 1.5 mg/kg. The intensity of fasciculations and intubating conditions were assessed using a four-point rating scale. In addition, the severity of myalgia was assessed using a four-point rating scale in the postanesthesia care unit and at 24 hours postoperatively. No patient complained of any side effects after the administration of the study drug. Fasciculations were observed less frequently (p < 0.05) in the d-tubocurarine and rocuronium groups compared with the placebo and cisatracurium groups. However, there was no difference between the d-tubocurarine group and the rocuronium group (21% vs. 10%, respectively). Although fasciculations occurred less frequently in the cisatracurium group than in the placebo group (59% vs. 85%, respectively), this difference did not reach statistical significance. There was no difference among the four groups in the intubating conditions or the incidence of postoperative myalgia.

Conclusion: Pretreatment with rocuronium and d-tubocurarine was superior to cisatracurium in preventing succinylcholine-induced fasciculations. However, pretreatment did not have any effect on the incidence of myalgia after ambulatory surgery.     

Competition between acetylcholine and a nondepolarizing muscle relaxant for binding to the postsynaptic receptors at the motor end plate: simulation of twitch strength and neuromuscular block

The goal of the study was to simulate twitch strength and neuromuscular block produced by nondepolarizing muscle relaxants. Methods: In the proposed model, affinities of the two binding sites at a single postsynaptic receptor for acetylcholine (A) and the muscle relaxant (D) define the formation of three complexes with A only, three complexes with D only, and two complexes with both A and D. Twitch strength was postulated to be a function of the receptors with both binding sites occupied by A, and two constants. Neuromuscular block (NMB) was calculated from NMB=1-twitch. Results: Stimulus-induced release of A results in rapid, but transient, changes in the concentrations of free A, the eight complexes, and the unoccupied receptors. Muscle relaxants that display either a congruous or an inverse pattern of affinities for the binding sites relative to those of A produce NMB vs. [D] curves with slightly different slopes but markedly different estimates for IC50. Depending on the number of activated receptors at the end plates of muscle fibers, the simulations represent the distributions of contracting fibers in a whole muscle. Conclusion: Simulations of competition between A and D for binding to two sites at a receptor reveal that the potencies of muscle relaxants, defined by IC50, and the slopes of the NMB vs. [D] curves depend on (1) the affinities of D for the two binding sites, (2) the orientation of the affinities relative to those of A, and (3) the affinities of A for the same two sites.     

Use of rapacuronium in a child with spinal muscular atrophy

We report the case of an 18-month-old girl with spinal muscular atrophy (SMA) that received 1 mg·kg^–1 rapacuronium for laryngospasm during induction of anaesthesia. Within 15 min, we observed some diaphragmatic recovery and, after emergence from anaesthesia, the child demonstrated adequate respiratory efforts. However, the child showed diminished strength of the upper extremity muscles. Since the preoperative workup had revealed bulbar symptoms and laryngeal function could not be easily assessed, the patient was kept intubated until upper extremity strength had returned to preoperative levels. Small doses of midazolam had been given to reduce the patient's anxiety but the patient was extubated within 5 h without any complications. Train of four (TOF) monitoring of the right adductor pollicis muscle, performed during anaesthetic recovery, was equivocal. In SMA, muscle groups are differentially affected so that TOF responses may be inconclusive and not reflect the state of the upper airway muscles. To our knowledge, this is the first report of use of a nondepolarizing neuromuscular blocking agent in a child with SMA.     

Rocuronium and anaphylaxis – a statistical challenge

Drug induced anaphylaxis is frequently attributed to the use of muscle relaxants during anaesthesia. Recently The Norwegian Medicines Agency recommended that rocuronium bromide (Esmeron) be withdrawn from routine practice due to frequent reports of anaphylaxis. Over a period of two and a half years approximately 150,000 patients received rocuronium as part of their anaesthesia. In this period the Norwegian drug authorities received 29 reports of anaphylaxis or anaphylactoid reactions in patients treated with rocuronium. This is in stark contrast to the situation in other Nordic countries where a total of only seven cases of anaphylaxis in approximately 800,000 patients treated with rocuronium had been recorded by December 2000. This situation highlights the many potential problems of the surveillance of adverse drug reactions: reporting bias may lead to an over-estimate of the risk of one drug compared to another, and the possibility of under-reporting of adverse events (due to a weak reporting culture) further limit the validity of such comparisons. The surveillance of adverse drug reactions also represents a statistical challenge. While adverse event reports may help us to estimate the anaphylaxis rate we need to appreciate the uncertainty of such estimates. Adverse reactions are rare, random, and mostly independent events, resulting from the successive exposure of patients to a low risk intervention. The frequency distribution of adverse events will therefore conform to that of a Poisson process. The resulting Poisson distribution may inform us about the variability of adverse event data. An understanding of these methodological problems and statistical challenges will allow anaesthesiologists to make informed decisions concerning the use of muscle relaxants and other drugs associated with severe adverse reactions.     

机械通气联合镇静肌松剂抢救成功肺闭锁综合征1例

患者,男,34岁。因＂气促伴神志不清1d＂于2013-06-20 13：00pm收入观察室。患者6月19日下午16：00pm左右感觉胸闷、心悸提前下班,到当地诊所就诊,当地医师见其气促,呼吸困难,建议呼＂120＂转上级医院就治,于19：00pm入我院抢救室,当时患者气促,烦躁不安,查血气分析：PH 7.07,PO2 45 mmHg,PCO2 89 mmHg,     

Succinylcholine: adverse effects and alternatives in emergency medicine

Succinylcholine has long been the favored neuromuscular blocking agent for emergent airway management because of its rapid onset, dependable effect, and short duration. However, it has a plethora of undesirable side effects, ranging from the inconsequential to the catastrophic. When patients requiring tracheal intubation present with potential contraindications to succinylcholine use, the emergency physician will need to substitute a rapid-onset nondepolarizing neuromuscular blocking agent, such as rocuronium or mivacurium. An understanding of the pharmacology of these agents is essential.     

持续泵注与间断静脉给予罗库溴铵的药效学比较

目的比较罗库溴铵持续泵注与间断给药的药效学特点,探讨其最佳的给药方式.方法50例ASAⅠ～Ⅱ级,无神经肌肉疾患,全麻下行择期手术的病人,随机分成罗库溴铵间断给药组(Ⅰ组)和持续泵注组(Ⅱ组),采用TOF刺激方式,监测拇内收肌的收缩反应.记录神经肌肉阻滞的最大阻滞时间及起效时间、恢复过程,并记录罗库溴铵的用药量.应用静脉麻醉药诱导及维持.全部病例均未予拮抗,使其在安静状态下自然恢复.当TOF恢复至T4/T1≥70%时,结束肌松监测,呼吸恢复满意后拔管.结果Ⅰ组维持肌松追加用药的间隔时间平均(29.24±6.26)min,各次追加的间隔时间之间无明显差异;Ⅱ组的平均泵注速率为(6.31±1.93)μg@kg-1@min-1,与Ⅰ组单位时间平均用量(5.43±1.46)μg·kg-1·