Cisatracurium-induced neuromuscular blockade in anticonvulsant treated neurosurgical patients

Patients treated with the anticonvulsants phenytoin or carbamazepine are resistant to steroidal neuromuscular blocking agents. We studied the effect of cisatracurium on onset, duration, and speed of recovery from neuromuscular blockade (NMB) in acutely anticonvulsant treated patients ([< 2 weeks] [AA]), chronically anticonvulsant treated patients ([> 2 weeks] [CA]) and patients not on anticonvulsants ([controls] [C]). After Internal Review Board approval, 10 AA, 14 CA, and 14 C neurosurgical patients were studied. Anesthetic induction was midazolam, fentanyl, and thiopental, and maintenance was fentanyl and 0.5 MAC isoflurane in O2. The evoked compound electromyogram of the hypothenar eminence was monitored (TOF supramaximal stimulus at 2 Hz every 20 seconds). Baseline TOF was established, then cisatracurium (0.2 mg/kg) was administered IV. Onset (time to maximal paralysis), duration [time to recovery of first twitch (T1) to 25% of baseline] and speed of recovery (time of recovery from 10%-25% of baseline) were recorded. Data were analyzed using ANOVA. Onset (C = 4 +/- 2, AA = 3 +/- 1, CA = 3 +/- 1.5 minutes) and duration (C = 69 +/- 13, AA = 64 +/- 19, CA = 59 +/- 19 minutes) were not different among the groups (P > .7). Speed of recovery was significantly faster in both AA (6 +/- 2 minutes) and CA (6 +/- 3 minutes) than in C (12 +/- 9 minutes) patients (P < .05). (Data = mean +/- SD). Onset and duration of cisatracurium-induced neuromuscular relaxation was not affected by acute or chronic anticonvulsant treatment, but speed of recovery was significantly faster. Frequent NMB monitoring is necessary to detect the greater speed of recovery in anticonvulsant-treated patients during cisatracurium muscle relaxation.     

Cisatracurium in cardiac surgery--continuous infusion vs. bolus administration

The aim of this study was the comparison of infusion vs. intermittent bolus administration of cisatracurium (CA) following cardiac surgery with regard to total intraoperative dose and time of recovery from neuromuscular blockade. From June 2005 to April 2006 sixty ASA II-III patients who were undergoing coronary bypass graft and valve replacement surgery, were equally divided and randomized to receive either intermittent bolus (Group A, n = 30) or continuous infusion (Group B, n = 30) of CA in Madani Heart Center in the Tabriz (Iran). Total intraoperative dose of CA and time to TOF ratio = 0.8 after operation were measured. Anesthesia technique in two groups was the same. All of the patients underwent cardiopulmonary bypass. Intensity of neuromuscular blockade maintained on one train-of-four (TOF) twitch response of adductor pollicis during operation. Mean received dose of CA was 32.8 +/- 20.6 micro/kg/hr in Group A and 89.7 +/- 39.4 micro/kg/hr in Group B (p = 0.003). Total intraoperative dose of CA was 23.6 +/- 4.9 mg in Group A and 39.2 +/- 10.1 mg in Group B (p = 0.001). Spontaneous recovery from neuromuscular blockade in ICU (TOF ratio = 0.8) was reached in 43.8 +/- 9.2 min in Group A, and 64.2 +/- 15.1 min in Group B (p = 0.0001). Intubation time in ICU was not significantly different (Group A = 8.3 +/- 5.1 hrs vs. Group B = 10.2 +/- 6.2 hrs, p = 0.256). These results support the intermittent bolus administration of cisatracurium in cardiac surgery following cardiopulmonary bypass.     

The effect of cisatracurium and rocuronium on cisatracurium precurarization and the priming principle

STUDY OBJECTIVE: To demonstrate the effect of administering a precurarizing dose of cisatracurium or rocuronium on the speed of onset of cisatracurium, and to review the possible mechanisms and value of the priming principle. DESIGN: Double-blind, randomized, controlled trial. SETTING: Inpatient anesthesia in a university teaching hospital. PATIENTS: 90 ASA physical status I and II patients undergoing elective surgery requiring endotracheal intubation. INTERVENTIONS: Three groups of 30 patients each were investigated. Following induction of anesthesia with fentanyl and propofol, Group 1 received cisatracurium 0.015 mg.k(-1), Group 2 received rocuronium 0.09 mg. kg(-1), and Group 3 (control) received normal saline. Six minutes after priming, Groups 1 and 2 received cisatracurium 0.135 mg. kg(-1) whereas Group 3 received cisatracurium 0.15 mg. kg(-1). MEASUREMENTS AND MAIN RESULTS: In each group, first twitch height and the train-of-four ratios were recorded every 10 seconds after the initial priming dose. Intubation was attempted after the first twitch height became less than 15% of baseline. The decrease in the train-of-four ratios at 6 minutes was 0.97 for cisatracurium and 0.85 for rocuronium. The onset of muscle relaxation was significantly faster after priming with cisatracurium and rocuronium (71.7 +/- 21.3 and 65 +/- 19.8 sec, respectively) compared with control (148.7 +/- 43.1 sec). Females receiving both muscle relaxants had a faster onset of paralysis than did males (65.9 +/- 20.6 vs. 79.2 +/- 20.6 and 55 +/- 14.5 vs. 71.7 +/- 20.4 sec). Intubation conditions were either excellent or satisfactory in all patients. CONCLUSIONS: Six minutes after precurarization, there is no significant difference between rocuronium and cisatracurium when used as priming drugs. An even faster onset time with both drugs was demonstrated in females. The use of priming doses of 25% to 30% of ED(95) may cause symptomatic muscle weakness. The mechanisms of the priming principle are discussed.     

Mivacurium: dose-response relationship and administration by repeated injection or infusion.

The dose-response relationship and neuromuscular blockade after infusion or repeated injection of mivacurium were studied in 65 patients in nitrous oxide-narcotic anesthesia. The ED95 (twitch tension) was determined in 45 patients by intravenous injection of a single bolus of 30, 39, 47, 54, or 60 micrograms/kg (9 patients per dose). Another 20 patients received an initial bolus of 2 x ED95 followed either by an infusion started at 5% twitch recovery (i.e., 95% depression) and adjusted to sustain 95% twitch depression (n = 10) or by repeated injection of 0.6 x ED95 whenever twitch tension had recovered to 25% of control (n = 10). Five patients in each of these two groups received 7 micrograms/kg of neostigmine at 25% twitch recovery, and the others recovered twitch tension spontaneously. The mean ED95 was 73 micrograms/kg. A 2 x ED95 bolus was followed by complete twitch depression within 2.2 +/- 0.7 min. The mean infusion rate resulted in 6 +/- 2 micrograms.kg-1.min-1. The ensuing recovery index was 6 +/- 3 min. A 6 +/- 2 min recovery index was found after up to 10 repeat injections given every 9 +/- 3 min. There was no significant effect of neostigmine in both groups. In conclusion, the recovery indices after the infusion or repeat injection of near-equal doses of mivacurium were identical.     

Influence of neostigmine on the course of neuromuscular blockade with rocuronium or cisatracurium: a randomized, double-blind trial

OBJECTIVES: To compare the time-course of neuromuscular blockade with rocuronium or cisatracurium during intravenous anesthesia, in terms of both the time to spontaneous recovery or time to reversal after administration of neostigmine. MATERIAL AND METHODS: Patients classified as ASA 1-2 were randomized to receive blinded administration of a single injection of twice the 95% effective dose of rocuronium or cisatracurium for general anesthesia, and then neostigmine plus atropine at recovery of the first train-of-4 (TOF) twitch at 5% or 25%, or normal saline solution as placebo at recovery of the first TOF twitch at 25%. The neuromuscular blockade was monitored by acceleromyography. Intergroup comparisons were carried out by Student t test and analysis of variance. RESULTS: Sixty patients were enrolled. Mean (SD) time to onset was faster with rocuronium at (1.04 [0.32] minutes) compared with cisatracurium at (2.58 [0.81] minutes) and duration was shorter: time to the first twich at 5% was 30 (6.4) minutes with rocuronium and 38.1 (9.7) minutes with cisatracurium. The total duration of blockade (time to the 80% TOF ratio) was also shorter with rocuronium when the neuromuscular blockade was reversed, but there were no differences in the time to block reversal when neostigmine was not used: 62 (18.9) minutes to recovery from the rocuronium blockade vs 66.96 (15.9) minutes to recover from a cisatracurium blockade. A high percentage of patients had less than an 80% TOF ratio at 60 and 90 minutes of administration of the neuromuscular blockerswhen reversal was not used (patients receiving rocuronium, 60% at 60 minutes, and 20% at 90 minutes; patients receiving cisatracurium, 80% at 60 minutes, and 40% at 90 minutes). CONCLUSION: Not antagonizing a rocuronium- or cisatracurium-induced neuromuscular blockade in surgical procedures lasting less than 90 minutes can lead to a high percentaje of residual blockade (TOF ratio <80%).     

Large bolus dose vs. continuous infusion of cisatracurium during hypothermic cardiopulmonary bypass surgery

BACKGROUND AND OBJECTIVE: We investigated whether a high bolus dose of cisatracurium (8x ED95) given at induction can provide muscle relaxation for the major part of a cardiac procedure with hypothermic cardiopulmonary bypass, avoid important postoperative residual curarization and cause no waste of product. METHODS: Twenty patients were randomly assigned either to Group 1 (n = 10) or Group 2 (n = 10). Those in Group 1 were given cisatracurium in a high bolus dose (0.4 mg kg(-1)). Those in Group 2 received cisatracurium 0.1 mg kg(-1) at induction followed after 30 min by a continuous infusion of cisatracurium. As an escape medication in case of patient movement, a bolus dose of cisatracurium 0.03 mg kg(-1) was given. RESULTS: In Group 1 (large cisatracurium bolus dose), the clinical duration of effect (until T1/T0 = 25%) was 110 min. Six of 10 patients in Group 1 required additional boluses of cisatracurium intraoperatively. Four of these six had received an additional bolus near the end of surgery and had a train-of-four (TOF) ratio = 0 at the end. The other four patients in Group 1 had a final TOF ratio >0.9. In Group 2 (continuous cisatracurium infusion), only two patients had a TOF ratio >0.9 at the end of surgery, no patient moved and none received additional boluses. The total amount of cisatracurium used in the bolus and infusion Groups was 34.5 +/- 7.8 and 21.3 +/- 5.7 mg, respectively (P = 0.0004). CONCLUSIONS: For continued neuromuscular block during hypothermic cardiac surgery, a high bolus dose of cisatracurium appears to be safe, although it is not an alternative to a continuous infusion, as its neuromuscular blockade does not cover the intraoperative period and a high incidence of movements occurs. In the patients who received a high bolus dose of cisatracurium, postoperative residual curarization appeared after additional boluses had been given. The consumption of cisatracurium by high bolus was significantly greater than with continuous infusion.     

Comparison of the neuromuscular blocking effect of cisatracurium and atracurium on the larynx and the adductor pollicis

BACKGROUND: Cisatracurium unlike atracurium is devoid of histamine-induced cardiovascular effects and this alone would be the greatest advantage in replacing atracurium for the facilitation of tracheal intubation. On the other hand, 2 ED(95) doses of cisatracurium (100 micro g/kg) do not yield satisfactory intubating conditions such as those seen with equipotent doses of atracurium and therefore the recommended intubating dose of cisatracurium is 3 ED(95). To understand this discrepancy better, we evaluated the potency and onset of atracurium and cisatracurium directly at the larynx adductors in humans. METHODS: The study was conducted in 54 patients (ASA class I or II) undergoing peripheral surgery requiring general anesthesia. Cisatracurium 25-150 micro g/kg or atracurium 120-500 micro g/kg intravenous (i.v.) boluses doses were administered during anesthesia with propofol, nitrous oxide, oxygen and fentanyl. Neuromuscular block was measured by electromyography (single twitch stimulation every 10 s) at the larynx and the adductor pollicis. The dose-response effect measured at both muscles included maximum neuromuscular blockade achieved (Emax), the time to maximum depression of twitch height (onset) and time to spontaneous recovery of the twitch height to 25%, 75% and 90% (T25, T75, T90) of control value. RESULT: The onset at the larynx was of 196 +/- 28 s after the 100 micro g/kg cisatracurium dose compared with 140 +/- 14 s after the 500 micro g/kg atracurium dose (P < 0.05). Emax at the larynx was 92 +/- 1% and 98 +/- 1% after 100 micro g/kg cisatracurium and 500 micro g/kg atracurium, respectively (P < 0.05). The time to onset of maximum suppression Emax = 100 +/- 0% after a 150 micro g/kg cisatracurium dose was 148 +/- 29 s. At the larynx, the ED(50) was 25 micro g/kg for cisatracurium and 180 micro g/kg for atracurium and the ED(95) was 87 micro g/kg for cisatracurium compared with 400 micro g/kg for atracurium. CONCLUSION: The slow onset time at the laryngeal muscles after cisatracurium can be explained by the higher potency as compared with atracurium.     

Pharmacodynamic interactions between cisatracurium and rocuronium

The onset and duration of maintenance doses of neuromuscular blocking drugs may be influenced by the original neuromuscular blocking drug used. We assessed the effect of the interaction between steroidal and benzo-isoquinolinium compounds on the clinical duration of maintenance doses of cisatracurium. Sixty adult patients undergoing anesthesia with isoflurane, nitrous oxide, and oxygen were randomized to receive the following: Group I = rocuronium 0.6 mg/kg followed by cisatracurium 0.03 mg/kg when the first twitch in the train-of-four (TOF) recovered to 25%, Group II = cisatracurium 0.15 mg/kg followed by cisatracurium 0.03 mg/kg, and Group III = rocuronium 0.6 mg/kg followed by rocuronium 0.15 mg/kg. Neuromuscular blockade was monitored using acceleromyography (TOF-Guard, Boxtel, The Netherlands). The clinical duration (mean +/- SD) of the first 2 maintenance doses was 41 +/- 10, 31 +/- 7++, and 25 +/- 8++ min, and 39 +/- 11, 30 +/- 6+, 29 +/- 9* min in Groups I-III, respectively (*P < 0.05, +P < 0.01, ++P < 0.001; Group I versus II and III). Thus, the clinical duration of the first two maintenance doses of cisatracurium was prolonged when administered after rocuronium. IMPLICATIONS: We assessed the clinical effect of administering cisatracurium after an intubating dose of rocuronium in 60 patients undergoing isoflurane/nitrous oxide and oxygen anesthesia. The clinical duration of the first two maintenance doses of cisatracurium administered after rocuronium was significantly prolonged. This supports the contention that combinations of structurally dissimilar neuromuscular blocking drugs result in a synergistic effect.     

Atracurium and vecuronium: repeated bolus injection versus infusion.

The purpose of this study was to compare the characteristics of recovery from neuromuscular blockade after either atracurium or vecuronium given by intravenous infusion or by repeated injection. Four groups of 10 patients each were studied during nitrous oxide narcotic anesthesia. An initial intravenous dose of 2 x ED95 of either muscle relaxant was followed by an intravenous infusion started at 5% recovery of control twitch tension and adjusted for 95% block or by repeated injection of 0.6 x ED95 administered whenever twitch tension had returned to 25% of control. There were no significant differences between the maintenance doses required based on method of administration: atracurium repeated injection, 1.6 +/- 0.3 x ED95 h-1; atracurium infusion, 1.7 +/- 0.3 x ED95 h-1; vecuronium repeated injection, 1.8 +/- 0.5 x ED95 h-1; and vecuronium infusion, 1.6 +/- 0.4 x ED95 h-1. Nevertheless, differences of up to 20 min were noted in the recovery indices in the following order: atracurium repeated injection = atracurium infusion less than vecuronium repeated injection less than vecuronium infusion. A single dose of neostigmine (7 micrograms/kg) significantly reduced the recovery indices, thereby eliminating their differences.     

Total intravenous anesthesia with remifentanil, propofol and cisatracurium in end-stage renal failure

PURPOSE: To compare recovery parameters of total intravenous anesthesia (TIVA) with remifentanil and propofol, hemodynamic responses to perioperative events, and pharmacodynamic parameters of cisatracurium in 22 end-stage renal failure and 22 normal renal function patients. METHODS: Anesthesia was induced with 2-3 mg x kg(-1) propofol and 1 microg x kg(-1) remifentanil and maintained with 75 microg x kg(-1) x min(-1) propofol and propofol initial infusion of 0.2 microg x kg(-1) x min(-1) propofol. Arterial pressure and heart rate were maintained by remifentanil infusion rate adjustments. The first twitch (T1) was maintained at 25% by an infusion of cisatracurium. RESULTS: There was no difference in the time to maintenance of adequate respiration, date of birth recollection, first analgesic administration, between the renal failure (4.8+/-2.5, 7.8+/-3.2, 12.3+/-5.3 min respectively) and the control group (5.2+/-2.8, 8.1+/-3.1, 12.7+/-5.5 min): nor were there any differences in the time to 25% T1 recovery, T1 recovery from 25% to 75%, or cisatracurium infusion rate between the renal failure group (32.1 +/-10.8 min, 18.2+/-5.5 min, 0.89+/-0.29 microg x kg(-1) min(-1) respectively) and the control group (35.9 (7.9 min, 18.4+/-3.8 min, 0.95+/-0.22 microg x kg(-1) x min(-1)). CONCLUSION: End-stage renal failure does not prolong recovery from TIVA with remifentanil and propofol, or the recovery from cisatracurium neuromuscular block.     

顺式阿曲库铵不同用药方式对老年全凭静脉麻醉肌松作用的影响

目的 探讨顺式阿曲库铵不同用药方式对老年患者全凭静脉麻醉肌松作用的影响.方法 60例掸期在全麻下行普外科手术的老年患者,ASA I～Ⅱ级.年龄7l～87岁,随机分为A组(η=20)和B组(η=40),其中B组再随机分为B1组(η=20)和B2组(η=20).肌松诱导:A组单次予顺式阿曲库铵0.2 mg·kg-1静注;B...     

Postoperative residual curarization with cisatracurium and rocuronium infusions

BACKGROUND AND OBJECTIVE: Monitoring of neuromuscular blockade still often relies on clinical judgement. Moreover, there are substantial national differences in the use of agents to 'reverse' their effects. We investigated the recovery characteristics and incidence of postoperative residual curarization after cisatracurium and rocuronium infusions for long duration interventions without systematic antagonism. METHODS: In 30 patients undergoing major surgery, we measured infusion dose requirements for rocuronium and cisatracurium during propofol anaesthesia. Infusions were discontinued at the beginning of surgical closure; spontaneous recovery of neuromuscular function was awaited in both groups. Neostigmine (50 microg kg(-1)) was administered only when a patient started to wake without a train-of-four ratio (TOF) of 0.9. RESULTS: In the cisatracurium and rocuronium groups, four (27%) and one (7%) patients, respectively, had a TOF ratio > or = 0.9 at the end of surgery. The TOF ratio in each group at that time was 51 +/- 32% for cisatracurium and 47 +/- 31% for rocuronium (P = 0.78). Six patients (40%) in the cisatracurium group and seven (47%) in the rocuronium group required neostigmine. The TOF ratio at the time of reversal was 63 +/- 7% for cisatracurium and 40 +/- 19% for rocuronium (P = 0.01). The time interval between the end of surgery and a TOF ratio of 0.9 was 10 +/- 9 min for cisatracurium and 18 +/- 13 min for rocuronium (P = n.s.). CONCLUSIONS: Patients receiving a cisatracurium or rocuronium infusion have a high incidence of postoperative residual curarization when the block is not antagonized. When 'reversal' is not attempted, cisatracurium seems to be safer than rocuronium.     

Duration and recovery profile of cisatracurium after succinylcholine during propofol or isoflurane anesthesia

Study Objective: To determine the duration and recovery profile of maintenance doses of cisatracurium besylate following succinylcholine, and during propofol or isoflurane anesthesia.

Design: Randomized, open-label study.

Setting: Operating suite of a university-affiliated medical center.

Patients: Forty ASA physical status I and II adult patients having elective surgery with general anesthesia lasting longer than 90 minutes.

Interventions: Following a standardized induction sequence, a baseline electromyogram (EMG) was obtained. An intubating dose of intravenous (IV) succinylcholine 1.0 mg/kg was administered. Ventilation was maintained with a face mask until the first twitch (T₁) of the evoked train-of-four (TOF) reached 10% of control when tracheal intubation was performed. Spontaneous recovery from neuromuscular blockade was allowed to occur until the first twitch returned to 25% of control. Patients then were randomized to receive cisatracurium as follows. Group 1: 0.025 mg/kg [0.5 × 95% effective dose (ED₉₅)]; Group 2: 0.05 mg/kg (ED₉₅); Group 3: 0.05 mg/kg (ED₉₅); and Group 4: 0.1 mg/kg (2×ED₉₅). Anesthesia for Groups 1 and 2 were maintained with isoflurane 1% to 2%, 66% nitrous oxide (N₂O) in oxygen (O₂), and in Groups 3 and 4, anesthesia was maintained with propofol 80 to 160 μg/kg/min, 66% N₂O in O₂. The TOF-evoked EMG was recorded at 10-second intervals. The time for the evoked EMG to spontaneously return to 25%, 50%, and 75% of the original baseline was recorded.

Measurements and Main Results: There were 10 patients in each of the four groups. The duration of action of cisatracurium 0.05 mg/kg (ED₉₅) after an intubating dose of succinylcholine is 24.5 ± 10 minutes and 21.3 ± 9 minutes during anesthesia maintained with isoflurane and propofol, respectively. Doubling the dose of cisatracurium resulted in approximately twice the duration of action (40.2 ± 7 min) during propofol anesthesia. Following a dose of cisatracurium 0.025 mg/kg (0.5×ED₉₅), the T₁ of the EMG-evoked response did not decrease below 25% in 7 of 10 patients.

Conclusion: Following succinylcholine, the duration of action of a single dose of cisatracurium 0.05 mg/kg is 20 to 25 minutes during anesthesia maintained with propofol or isoflurane. The duration and recovery profile of cisatracurium is dose dependent during propofol and isoflurane anesthetics. Cisatracurium 0.025 mg/kg is an inadequate maintenance dose following recovery from succinylcholine and it fails to provide adequate surgical relaxation.     

Vecuronium infusion dose requirements during fentanyl and halothane anesthesia in humans

Steady-state infusion rate requirements of vecuronium were determined in 29 patients during either halothane-nitrous oxide or fentanyl-nitrous oxide anesthesia at different levels of neuromuscular block. During N2O-halothane anesthesia (end-tidal concentration, 0.5%), the infusion rate necessary for a steady-state (defined as unchanging twitch height and infusion rate for at least 20 min) 50% depression of twitch force was 28.8 +/- 5.4 (mean +/- SD) (n = 8) and 47.6 +/- 9.7 micrograms . kg-1 . hr-1 (n = 6) at 90% reduction of twitch force. During N2O-fentanyl anesthesia, the steady-state infusion rate required for 50 and 90% decrease of twitch force was 56.3 +/- 20.0 (n = 9) and 74.8 +/- 16.0 micrograms . kg-1 . hr-1 (n = 6), respectively. The variances of vecuronium steady-state infusion dose requirements were smaller in the halothane groups than in the fentanyl anesthesia groups. The steady-state vecuronium infusion dose requirements during fentanyl anesthesia were greater than the mean infusion dose requirements during halothane anesthesia at equivalent levels of twitch depression.     

Cisatracurium neuromuscular block at the adductor pollicis and the laryngeal adductor muscles in humans

We have compared the dose-response relationship (n = 30) and time course of neuromuscular block (n = 20) of cisatracurium at the laryngeal adductor and the adductor pollicis muscles. ED95 values for cisatracurium were 66.8 (95% confidence interval 61.3-72.3) micrograms kg-1 at the larynx and 45.2 (42.1-48.3) micrograms kg-1 at the adductor pollicis muscle (P < 0.0001). After administration of cisatracurium 0.1 mg kg-1, onset time was 2.7 (2.2-3.2) min at the larynx and 3.9 (3.0- 4.8) min at the adductor pollicis (P < 0.0001). Time to 95% recovery of the first twitch of the TOF was 26.9 (20.1-33.7) min and 45.6 (39.7- 51.5) min, respectively (P < 0.0001). We found that the laryngeal adductors were more resistant to the action of cisatracurium than the adductor pollicis muscle, but onset and recovery were faster at the larynx.      

Accelerated reversal of atracurium blockade with divided doses of neostigmine

The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of neuromuscular blockade was investigated. Neostigmine 0.05 mg X kg-1 was administered either in a single bolus dose (Group I, n = 16) or in an initial dose of 0.01 mg X kg-1 followed three minutes later by 0.04 mg X kg-1 (Group II, n = 16) for antagonism of atracurium-induced blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. The mean time (+/- SD) from the first injection of the drug until the train-of-four (TOF) ratio value had reached 0.75 was significantly shorter in Group II (p less than 0.05) than in Group I (391.8 +/- 83.3 and 468.6 +/- 150.3 seconds respectively). The rate of TOF ratio recovery was 2.5 times faster after neostigmine administration in divided doses. It is concluded that administration of neostigmine in divided doses, as described in this study, produced a significantly faster reversal of residual atracurium-induced neuromuscular blockade as compared to a single bolus administration.     

The clinical neuromuscular pharmacology of mivacurium chloride (BW B1090U). A short-acting nondepolarizing ester neuromuscular blocking drug

Mivacurium chloride (BW B1090U), a bis-benzylisoquinolinium diester compound, was found to undergo hydrolysis in vitro by purified human plasma cholinesterase in a pH-stat titrator at 88% of the rate of succinylcholine at pH 7.4, 37 degrees C and 5 microM substrate concentration. In 72 consenting ASA Physical Status I-II patients receiving nitrous oxide/oxygen-narcotic-thiopental anesthesia, the neuromuscular blocking effect of mivacurium was assessed following bolus doses from 0.03 to 0.30 mg/kg, as well as during and following continuous infusions from 35 to 324 min in length. The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.08 mg/kg. At 0.1 mg/kg, 96% block developed, onset to maximum block required 3.8 +/- 0.5 min, and recovery to 95% twitch height occurred 24.5 +/- 1.6 (SE) min after injection. At 0.25 mg/kg, onset was 2.3 +/- 0.3 min; 95% recovery developed within 30.4 +/- 2.2 min, an increase in duration of action of only 24% versus 150% higher dosage. Comparative recovery indices from 5 to 95% or from 25 to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.3 mg/kg (range 12.9 to 14.7 and 6.6 to 7.2 min, respectively). In 38 patients who received mivacurium by continuous infusion (duration 88.1 +/- 7.1/47.1 min, SE/SD) for maintenance of 95 +/- 4% twitch inhibition, the mean 5-95% and 25-75% recovery indices after discontinuation of infusion were 14.4 +/- 0.6 and 6.5 +/- 0.3 min (P greater than 0.5 vs. all single bolus doses). The train-of-four (T4) ratio, within 2.6 +/- 0.5 min after 95% twitch recovery following bolus doses, averaged 79.5 +/- 1.8% (n = 32). Similarly, after discontinuation of infusions, the T4 ratio reached 73.4 +/- 1.9% within 3.4 +/- 1.9 min after 95% twitch recovery (n = 33). Antagonism of residual block was seldom indicated, but, to test ease of reversal, eight patients electively received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at 67 to 93 (76.6 +/- 3.5) % block. Twitch returned to 95% of control within 4.5 to 9.5 (6.3 +/- 0.5) min after neostigmine. Mivacurium may offer increased versatility in providing clinical muscle relaxation in a variety of situations. Further studies seem appropriate.     

Pharmacokinetics and pharmacodynamics of a 0.1 mg/kg dose of cisatracurium besylate in children during N2O/O2/propofol anesthesia

We studied the pharmacokinetics and pharmacodynamics of cisatracurium in 9 children (mean weight, 17.1 kg) aged 1-6 yr (mean, 3.75 yr) during propofol-nitrous oxide anesthesia. Neuromuscular monitoring was performed. Venous samples were taken before injection of a 0.1 mg/kg dose of cisatracurium and then at 2, 5, 10, 30, 60, 90, and 120 min. Cisatracurium plasma concentrations were determined by high performance liquid chromatography. Onset time was 2.5 +/- 0.8 min, recovery to 25% of baseline twitch height was 37.6 +/- 10.2 min, and the 25%-75% recovery index was 10.9 +/- 3.7 min. Distribution and elimination half-lives were 3.5 +/- 0.9 min and 22.9 +/- 4.5 min, respectively. Steady-state volume of distribution (0.207 +/- 0.031 L/kg) and total body clearance (6.8 +/- 0.7 mL/min/kg) were significantly larger than those published for adults. Pharmacodynamic results were comparable to those obtained in pediatric studies during halothane or opioid anesthesia with the exception of a longer recovery to 25% baseline. Although the plasma-effect compartment equilibration rate constant was twofold faster (0.115 +/- 0.025 min(-1)) than that published for cisatracurium in adults, the effect compartment concentration corresponding to 50% block was similar (129 +/- 27 ng/mL).     

Assessment of neuromuscular and haemodynamic effects of cisatracurium and vecuronium under sevoflurane-remifentanil anaesthesia in elderly patients

BACKGROUND AND OBJECTIVE: Neuromuscular block times, quality of muscle relaxation for tracheal tube insertion, and the haemodynamic effects after cisatracurium and vecuronium under sevoflurane-remifentanil anaesthesia were compared in elderly patients. METHODS: The study was performed in 40 patients over 65 yr of age. Anaesthesia was induced with thiopental, and maintained with sevoflurane in N2O/O2 and remifentanil. Cisatracurium 0.15 mg kg(-1) or vecuronium 0.1 mg kg(-1) were administered after induction. Intubation was attempted when neuromuscular block was 95%. Onset time, clinical duration of action, recovery index, spontaneous recovery time and tracheal intubation conditions were assessed. Haemodynamic parameters were also monitored. RESULTS: The average ages of the patients were 72.5 +/- 5.1 and 73.6 +/- 6.3 in the cisatracurium and vecuronium groups, respectively. Onset time was significantly shorter after vecuronium, 158 +/- 34 s vs. 200 +/- 50s, respectively. Recovery index was significantly shorter after cisatracurium, 19.5 +/- 7.5 s vs. 33.7 +/- 18.6 s (P < 0.05). Clinical duration and spontaneous recovery time were similar in both groups as well as haemodynamic variables. CONCLUSIONS: In elderly patients, vecuronium has a faster onset time while cisatracurium has a shorter recovery index under sevoflurane-remifentanil anaesthesia.