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.     

A comparison of accelerometric monitoring by TOF Watch® SX and electromyographic monitoring by Tetragraph® for recovery from neuromuscular blockade

BackgroundNeuromuscular monitoring has become a standard of care for management of anesthesia. While acceleromyography (AMG) is the most common technology used in clinical practice, guidelines suggest that electromyographic (EMG) devices are ideal for quantitative neuromuscular monitoring. The Tetragraph® is an EMG monitor that has recently been marketed.Study objectiveThe aim of this study is to assess the agreement during recovery from neuromuscular blockade of this new monitor with the TOF Watch® SX, and to compare intraobserver variability for the two devices.DesignSingle-center, prospective, observational clinical study.SettingOperating room.PatientsTwenty-three patients were enrolled and twenty patients were included in the analysis.InterventionA comparison of TOF-ratios measured sequentially from the same hand with the Tetragraph and TOF Watch SX was conducted during spontaneous recovery of neuromuscular function from patients that received rocuronium during surgery.Main outcome measuresWe used Bland-Altman plots for repeated measures to compare TOF-ratios obtained sequentially by the two devices. Subsequent measures with the same device were used to calculate intraobserver variability for each monitor.Main resultsThe bias between AMG and EMG for TOF-ratios range between 0.2 and 1.0 was 0.13 (95% CI 0.08 to 0.18) and the limits of agreement (LoA) were − 0.11 (95% CI -0.20 to −0.06) and 0.37 (95% CI 0.32 to 0.46), respectively. Agreement slightly improved for TOF-ratios higher than 0.8 compared with lower TOF-ratios: the bias was 0.12 (95% CI 0.08 to 0.17) and 0.13 (95% CI 0.08 to 0.19), respectively. EMG relative intraobserver variability was lower compared with AMG (2.0%, IQR 0.0% to 4.5% vs. 3.2%, IQR 1.2% to 6.0%, P = 0.001).ConclusionsBias between the TOF Watch SX and the Tetragraph TOF-ratios is in line with previous results for AMG and EMG monitors.     

Smoking increases the requirement for rocuronium

Purpose

To compare the potency of rocuronium in non-smokers and smokers during general anaesthesia.

Methods

In a randomized, open clinical study, 40 patients, 17–62 yr of age, were anaesthetized with propofol, alfentanil and nitrous oxide in oxygen. After obtaining individual dose-response curves for rocuronium, bolus doses of rocuronium were given to maintain neuromuscular block at 90–99% for 60 min. Evoked adductor pollicis electromyography (EMG) was used to monitor neuromuscular block.

Results

The ED₉₅ values (± SEM) for rocuronium were 460.5 ± 28.9 and 471.5 ± 22.1 μg·kg^?1 for nonsmokers and smokers, respectively (P:NS). However, doses of rocuronium to maintain 90–99% neuromuscular block (± SEM) were 620.1 ± 46.7 and 747.4 ± 56.0 μg·kg^?1·hr^?1 for non-smokers and smokers, respectively (P = 0.0504).

Conclusion

The results may indicate increased metabolism of rocuronium in smokers rather than increased requirement of rocuronium at the receptor site.     

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.     

ORIGINAL ARTICLE: Potency and recovery characteristics of rocuronium mixed with sodium bicarbonate

Sodium bicarbonate may be added to rocuronium to decrease pain on injection. However, this mixture may result in the formation of carbon dioxide bubbles. We investigated whether the addition of sodium bicarbonate to rocuronium alters neuromuscular blockade, in 120 patients randomly assigned to receive rocuronium mixed with saline or bicarbonate 8.4%, either in varying doses (for dose‐response measurements; 60 patients) or a fixed dose of 600 μg.kg^‐1 (for time‐course measurements; 60 patients). Sodium bicarbonate resulted in a left‐shift of the rocuronium dose‐response curve. The effective doses of rocuronium to produce 95% twitch depression were 331.6 (95% CI: 310.4–352.8) and 284.3 (95% CI: 262.0–306.6) μg.kg^?1 mixed with isotonic saline or sodium bicarbonate, respectively (p < 0.001). The mean (SD) onset times of rocuronium 600 μg.kg^‐1 were 3.6 (0.6) and 2.7 (0.5) min in the corresponding groups, respectively (p < 0.001). The mean (SD) times to 95% recovery were 35.8 (5.8) and 47.9 (7.1) min, respectively (p < 0.001). We conclude that the mixing of sodium bicarbonate with rocuronium enhances the potency, shortens the onset and prolongs the duration of action.     

Interaction between rosuvastatin and rocuronium in rat sciatic-gastrocnemius nerve-muscle preparation

Purpose

Long-term use of rosuvastatin may be associated with myotoxicity. Statins are one of the groups commonly found to be associated with neuromuscular weakness. The present study was designed to investigate the interaction between rosuvastatin and rocuronium in vivo by using a sciatic-gastrocnemius nerve-muscle preparation of rat.

Methods

In our study groups, animals received rosuvastatin 2 mg/kg for 14 and 28 days. Train of four (TOF) stimulation was applied to the sciatic nerve, and gastrocnemius muscle contractions were recorded in Wistar albino rats. Intravenous infusion of rocuronium was given until the twitch responses were abolished. We ultimately compared the effective dose required for a desired effect in 95% of the population (ED₉₅), duration 25 %, deep block, recovery index, and time for returning of TOF ratio to 0.9 between the active control and study groups.

Results

Chronic administration of rosuvastatin at a dose of 2 mg/kg for 28 days significantly reduced the ED₉₅ of rocuronium as compared to the active control group. Deep block and duration 25 % were increased by 3.5 and 2.5 times, respectively, compared to the active control group. The spontaneous recovery of neuromuscular block was delayed, as evidenced by the prolonged recovery index and increase in time required for a return of the TOF ratio to 0.9.

Conclusion

The neuromuscular blocking potency of rocuronium is increased and recovery is delayed in rats that pre-treated with rosuvastatin.     

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.     

Neuromuscular blocking effects of rocuronium during desflurane, isoflurane, and sevoflurane anaesthesia

Purpose

To determine the magnitude of the potentiation of rocuronium by desflurane, isoflurane and sevoflurane 1.5 MAC anaesthesia.

Methods

In a prospective, randomised, study in 80 patients, the cumulative dose-effect curves for rocuronium were determined during anaesthesia with desflurane, sevoflurane and isoflurane (with N₂O 70%, 15 min steady state) or total intravenous anaesthesia (TIVA) using propofol/fentanyl. Neuromuscular block was assessed by acceleromyography (TOF-Guard®) after train-of-four (TOF) stimulation of the ulnar nerve (2Hz every 12sec, 200 μsec duration), Rocuronium was administered in increments of 100 μg·kg^?1 until first twitch (T₁) depression > 95%.

Results

Rocuronium led to more pronounced T₁ depression with desflurane or sevoflurane anaesthesia than with TIVA. The ED₅₀ and ED₉₅ were lower during desflurane (95 ± 25 and 190 ± 80 μg·kg^?1) and sevoflurane (120 ±30 and 210 ± 40 μg·kg^?1) than with TIVA (150 ± 40 and 310 ± 90 μg·kg^?1) (P < .01), while the difference was not significant for isoflurane (130 ± 40 and 250 ± 90 μg·kg^?1). Following equi-effective dosing (T₁ > 95%) the duration to 25% T₁ recovery, recovery index (25/75), and TOF_0.70 was: 13.2 ± 1.8, 12.7 ± 3.4, and 26.9 ± 5.7 min during anaesthesia with desflurane; 15.5 ± 5.0, 11.4 ± 3.8, and 31.0 ± 6.0 min with sevoflurane; 13.9 ± 4.7, 10.7 ± 3.3, and 26.3 ± 8.9 min with isoflurane; and 13.9 ± 3.9, 11.3 ± 5.7, and 27.5 ± 8,2 min with TIVA anaesthesia (P: NS).

Conclusion

Interaction of rocuronium and volatile anaesthetics resulted in augmentation of the intensity of neuromuscular block but did not result in significant effects on duration of or recovery from the block.     

Pancuronium dose-response revisited

We were interested in determining the cumulative dose-response relationship of pancuronium in infants and children during nitrous oxide–halothane anaesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10 s intervals. Forty patients were divided into four equal groups according to age: 3–6 months, 7–12 months, 13–47 months and 48–83 months. The effective dose, ED₅₀ (mean ± SEM), of pancuronium in these age groups was 24 ± 2, 30 ± 2, 34 ± 3, 29 ± 2 μgμkg^-1, respectively; the ED₉₅ (mean ± SEM) was 45 ± 2, 52 ± 3, 62 ± 6, 62 ± 4 μgμkg^-1, respectively. The ED₉₅ of pancuronium was significantly less (P < 0.05) for infants from 3 to 6 months of age than for children from 13 to 83 months of age. Infants thus appear to be more sensitive than children to the neuromuscular blocking effects of pancuronium during halothane anaesthesia.     

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.     

术前急性高容量血液稀释对罗库溴铵量-效关系的影响

Objective To study the influence of preoperative acute hypervolaemic haemodilution (AHHD) on the dose-response relationship of rocuronium.Methods Forty patients were randomly allocated to AHHD group or control group (n=20).Anesthesia was maintained with propofol and remifentsnyl using TCI,and rocuronium was randomly given with one of six doses(60 μg/kg).AHHD was conducted with preoperative infusion of 15 ml/kg 6% hydroxyethyl starch at a rate of 30 ml/min.Neuromuscular function was assessed using an accelograph with train-of-four stimulation at wrist.The dose-response relationship of rocuronium was determined with cumulative dose-response technique.Results Hb,Hct,TPP and ALB decreased markedly (P＜0.05) after AHHD.AHHD did not result in a significant shift in rocuronium dose-response curve.There was no significant difference in ED50,ED90,and ED95 between the AHHD group[(192.1±24.9) μg/kg,(309.9±42.7) μg/kg,(322.0±44.4) μg/kg,respectively]and the control group [(178.5±34.7) μg/kg,(209.1± 47.8)μg/kg,(304.1±49.5) μg/kg,respectively].Conclusion These results demonstrate that the potency of rocuronium is not affected by AHHD,and rocuronium may become an ideal choice of relaxant in occasion of applying AHHD.     

Effective dose of dexmedetomidine as an adjuvant sedative to peripheral nerve blockade in elderly patients

Background

The median effective dose (ED₅₀) of sedative dexmedetomidine adjuvant to peripheral nerve block (PNB) has not yet been verified in elderly patients. This study assessed the ED₅₀ of intravenous dexmedetomidine for sedation in elderly patients who were undergoing total knee arthroplasty (TKA) with PNB.

Methods

Forty‐two patients aged 65–85 years were included and stratified into two groups according to age: young‐old group (aged 65–74 years) and middle‐old group (aged 75–85 years). After the PNB was performed, a pre‐calculated dose of dexmedetomidine was administered for 10 min. The Observer's Assessment of Alertness/Sedation scale, bispectral index score, blood pressure and heart rate were recorded. ED₅₀ values of dexmedetomidine for adequate sedation were estimated by the up‐and‐down method of Dixon and probit regression.

Results

The ED₅₀ of single‐dose dexmedetomidine adjuvant to PNB was 0.57 μg/kg (95% confidence interval [CI], 0.47–0.65) in the young‐old group and 0.38 μg/kg (95% CI, 0.28–0.46) in the middle‐old group. The ED₅₀ of dexmedetomidine differed significantly between the two groups (P < 0.001). In addition, no significant adverse hemodynamic or hypoxemic effects were noted.

Conclusion

We determined the ED₅₀ for sedation using intravenous dexmedetomidine adjuvant to PNB in elderly patients. The ED₅₀ of dexmedetomidine in the middle‐old group decreased by 33% compared with that in the young‐old group with a mean age difference of 11 years between the two groups.     

Rocuronium and sugammadex for rapid sequence induction of obstetric general anaesthesia

Background: Many anaesthetists use rocuronium in place of suxamethonium for rapid sequence induction (RSI). This is less common in obstetric anaesthesia as the duration of action of an effective dose of rocuronium exceeds most obstetric procedures. Sugammadex offers the possibility of rapidly reversing profound rocuronium neuromuscular blockade at the end of surgery. We aimed to determine whether rocuronium 1.2 mg/kg used for RSI in the obstetric population would provide good intubating conditions at 60 s and would be effectively reversed by sugammadex at the end of surgery. Methods: We present a prospective series of 18 patients who received rocuronium 1.2 mg/kg at induction of anaesthesia, monitored with a train‐of‐four ratio (TOF)‐Watch SX^®, and reversed using sugammadex 4 mg/kg. Results: The mean (95% CI) onset time of rocuronium was 71 (56–86) s, and the mean (95% CI) time to recovery of the TOF to ≥90%, after the administration of sugammadex 4 mg/kg at the end of surgery, was 86 (69–104) s. Conclusion: Rocuronium 1.2 mg/kg reversed by sugammadex appears to be effective in the obstetric population.     

The optimal dose of remifentanil for acceptable intubating conditions during propofol induction without neuromuscular blockade

Study ObjectiveTo determine the optimal remifentanil dose required to provide acceptable intubating conditions following induction of anesthesia with propofol without using neuromuscular blockade.DesignDose-response study.SettingOperating room of a university hospital.Patients50 ASA physical status 1 men, aged between 20 and 40 years, who were scheduled for general anesthesia.InterventionsIntubating conditions were evaluated according to the scoring system described by Viby-Mogensen et al. Successful intubation was defined as excellent or good.MeasurementsFor induction of anesthesia, an intravenous (IV) bolus dose of propofol 2.0 mg/kg was given over 30 seconds followed by the administration of predetermined IV remifentanil over 30 seconds; intubation was performed 90 seconds after completion of the remifentanil administration. The dose of remifentanil used for each patient was determined by the response of the previously tested patients, using the modified Dixon's up-and-down method (using 0.2 μg/kg as a step size). The first patient was tested with remifentanil 1.0 μg/kg. If intubation failed, the remifentanil dose was increased by 0.2 μg/kg; if intubation was successful, the dose was decreased by 0.2 μg/kg. Mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation were recorded during the study period.Main ResultsAccording to probit analysis, the effective dose of remifentanil in 50% (ED₅₀) and 95% (ED₉₅) of patients were 1.40 μg/kg and 2.40 μg/kg, respectively. Preintubation and postinduction HR and MAP values were lower than preinduction values (P < 0.001).ConclusionThe optimal bolus dose of remifentanil for acceptable intubating conditions was 2.40 μg/kg (95% confidence interval, 1.90-9.0 μg/kg) in 95% of patients during induction of anesthesia with propofol 2.0 mg/kg without neuromuscular blocking agents.     

Effects of different doses of remifentanil on the end-tidal concentration of sevoflurane required for tracheal intubation in children

We investigated the effects of different doses of remifentanil on the end‐tidal concentration of sevoflurane required for tracheal intubation in children without the use of neuromuscular blocking drugs. One hundred and thirty paediatric patients, aged 3–8 years, were randomly allocated to receive no remifentanil (group control) or remifentanil 0.1 μg.kg^?1.min^?1 (group remi_0.1), 0.2 μg.kg^?1.min^?1 (group remi_0.2), 0.3 μg.kg^?1.min^?1 (group remi_0.3). All patients were anaesthetised using 5% sevoflurane. After loss of eyelash reflex, remifentanil 1 μg.kg^?1 was injected over 1 min followed by an appropriate group‐dependent infusion and the end‐tidal sevoflurane concentration was changed. Predetermined end‐tidal sevoflurane concentrations for each group were determined using the Dixon up‐and‐down method. After the target concentration of sevoflurane was maintained for 5 min, the child’s trachea was intubated. Successful intubation was defined as excellent or good intubating conditions. The end‐tidal concentration (SD) of sevoflurane for successful tracheal intubation in 50% of children (ED₅₀) were 5.16 (0.22)% in control, 3.27 (0.18)%, 1.81 (0.20)% and 1.01 (0.11)%, in remi_0.1, remi_0.2, and remi_0.3 groups, respectively. Using probit analysis, the 95% effective dose (ED₉₅) of sevoflurane were 5.60% (95% CI 5.35–7.66), 3.77% (95% CI 3.45–7.74), 2.18% (95% CI 1.96–3.86), 1.19% (95% CI 1.06–1.82) in control, remi_0.1, remi_0.2, and remi_0.3 groups, respectively.     

肝移植术患者罗库溴铵不同给药方式肌松效果的比较

目的 比较肝移植术患者间断静脉注射(Ⅳ)、静脉输注(CI)和靶控输注(TCI)罗库溴铵的肌松效果.方法 拟行肝移植术的患者36例,性别不限,年龄21～63岁,体重48～80 kg,Child-Pugh评分7～9分,肝功能Child分级B或C级,随机分为3组(n=12):Ⅳ组、CI组和TCI组.采用TOF模式进行肌松监测,Ⅳ组:麻醉诱导时静脉注射罗库溴铵0.6 mg/kg,无肝前期T1恢复至25%时、无肝期和新肝期T4/T1(TOFR)恢复至25%时追加0.15 mg/kg.TCI组:麻醉诱导时靶控输注罗库溴铵,初始效应室靶浓度3μg/ml,调整靶浓度,维持T1 5%～10%;无肝期和新肝期开始时暂停TCI,随后以效应室靶浓度0.1μg/ml再次输注,调整靶浓度,维持T15%～10%.CI组:麻醉诱导时静脉注射罗库溴铵0.6 mg/kg,无肝前期以30μg·kg-1·min-1的速率开始静脉输注,调节输注速率,维持T1 5%～10%,无肝期和新肝期开始时暂停CI,随后以1μg·kg-1·min-1的速率静脉再次输注,调整输注速率,维持T15%～10%.各组于肌松达最大效应时行气管插管,于缝合腹膜后停止给药.记录麻醉诱导时罗库溴铵肌松起效时间、T1最大抑制程度和气管插管条件满意情况;记录各组无肝期T1 25%恢复时间及TOFR 25%恢复时间,新肝期停药后T125%恢复时间、TOFR 25%恢复时间、TOFR 75%恢复时间、TOFR90%恢复时间及恢复指数;记录罗库溴铵总用量.结果 与Ⅳ组比较,TCI组和CI组气管插管条件满意率、罗库溴铵总用量、麻醉诱导时罗库溴铵起效时间、T1最大抑制程度和各期肌松恢复情况差异均无统计学意义(P＞0.05).肌松效应监测图显示Ⅳ组各期罗库溴铵肌松效应波动较大,TCI组和CI组各期肌松效应较为平稳.结论 采用Ⅳ、CI和TCI给药时,肝移植术患者罗库溴铵肌松起效和恢复情况无差异,而采用TCI或CI给药时,肌松效应较Ⅳ更加平稳.     

Time course of rocuronium‐induced neuromuscular block after pre‐treatment with magnesium sulphate: a randomised study

Background: A previously published study suggested that pre‐treatment with magnesium sulphate (MgSO₄) had no impact on the speed of onset of rocuronium‐induced neuromuscular block. We set out to verify this assumption. Methods: Eighty patients (18–60 years) were randomly allocated to MgSO₄ 60 mg/kg or placebo (saline). Study drugs were given intravenously for 15 min before induction of anaesthesia with propofol, sufentanil and rocuronium 0.6 mg/kg. Anaesthesia was maintained with a target‐controlled propofol infusion. Neuromuscular transmission was measured using train‐of‐four (TOF)‐Watch SX^® acceleromyography. Results: Onset was analysed in 37 MgSO₄ and 38 saline patients, and recovery in 35 MgSO₄ and 37 saline patients. Onset time (to 95% depression of T1) was on average 77 [SD=18] s with MgSO₄ and 120 [48] s with saline (P<0.001). The total recovery time (DurTOF0.9) was on average 73.2 [22] min with MgSO₄ and 57.8 [14.2] min with saline (P<0.003). The clinical duration (Dur25%) was on average 44.7 [14] min with MgSO₄ and 33.2 [8.1] min with saline (P<0.0002). The recovery index (Dur25–75%) was on average 14.0 [6] min with MgSO₄ and 11.2 [5.2] min with saline (P<0.02). The recovery time (Dur25%TOF0.9) was on average 28.5 [11.7] min with MgSO₄ and 24.7 [8.4] min with saline (P=0.28). Conclusion: Magnesium sulphate given 15 min before propofol anaesthesia reduces the onset time of rocuronium by about 35% and prolongs the total recovery time by about 25%. Trial Registration: Clinicaltrials.gov identifier: NCT00405977.     

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.     

癫痫患者罗库溴铵95％有效量的测定

目的 通过测定癫痫患者罗库溴铵95％有效量(95％ effective dose,ED95),为癫痫患者合理应用罗库溴铵提供依据. 方法 选取择期行癫痫病灶切除术患者40例,ASA分级Ⅰ、Ⅱ级.根据罗库溴铵不同剂量按随机数字表法分为4组(每组10例):120 μg/kg组、180 μg/kg组、240 μg/kg组和300 μg/kg组.采用单次剂量注射法测定患者ED95,记录拇指内收肌“四个成串刺激(train of four stimulation,TOF)”第1个肌颤搐反应(T1)最大抑制的百分比及药物的起效时间,将最大抑制百分比进行概率单位转换,罗库溴铵的首次剂量做对数转换,用直线回归方法建立维库溴铵的剂量-反应曲线,计算出癫痫患者的罗库溴铵ED95值. 结果 各组间一般情况比较,差异无统计学意义(P＞0.05);不同剂量组起效时间比较,差异无统计学意义(P＞0.05),T1最大抑制程度随剂量增加而增加(P＜0.05),但240 μg/kg组和300 μg/kg组间差异无统计学意义(P＞0.05);癫痫患者罗库溴铵ED95值为445.3 μg/kg,高于目前正常人群广泛应用的ED95值300 μg/kg(P＜0.05). 结论 癫痫患者罗库溴铵的ED95值高于正常人群,在该类患者中应增加罗库溴铵的剂量约50％以取得与正常人群相同的肌松水平.     

Adenosine and adenosine uptake inhibitors potentiate the neuromuscular blocking action of rocuronium mediated by adenosine A1 receptors in isolated rat diaphragms

Background: Adenosine, which pre‐junctionally modulates neuromuscular transmission, and adenosine uptake inhibitors, which increase extracellular adenosine, have been used clinically. We investigated the effects of adenosine, dipyridamole and midazolam on the neuromuscular blocking action of rocuronium. Methods: Isometric twitch tensions of rat nerve‐hemidiaphragm preparations elicited by indirect (phrenic nerve) supra‐maximal stimulation at 0.1 Hz were evaluated (n=6 in all data). Results: Pre‐treatments with adenosine (0.1 and 1 μM) and CCPA (1 μM, adenosine A₁ receptor agonist), but not that with CGS21680 (0.5 μM, A₂ receptor agonist), shifted the rocuronium concentration–twitch tension curves to the left and decreased the rocuronium concentration for 50% twitch depression (IC₅₀) compared with the control (P<0.01). The leftward shift induced by 1 μM adenosine was inhibited by pre‐treatments with theophylline (50 μM, non‐selective adenosine receptor antagonist) and DPCPX (0.2 μM, A₁ receptor antagonist) but not by that with DPMA (5 μM, A₂ receptor antagonist). Pre‐treatments with dipyridamole and midazolam, adenosine uptake inhibitors, shifted the curve to the left and decreased IC₅₀ at supra‐therapeutic concentrations (10 and 2.5 μM, respectively) but not at clinical concentrations (2 and 0.5 μM, respectively), and the leftward shifts were inhibited by pre‐treatment with DPCPX (0.2 μM). Conclusion: The results indicate that adenosine potentiates the neuromuscular blocking action of rocuronium mediated by adenosine A₁ receptors and that supra‐therapeutic concentrations of dipyridamole and midazolam also potentiate the action of rocuronium by increasing endogenous adenosine concentration.