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Newer neuromuscular blocking agents: how do they compare with established agents?

Rapacuronium bromide (rapacuronium; ORG-9487) is a nondepolarising muscle relaxant (NMBA) with a low potency [90% effective dose (ED90) 1 mg/kg], which to some extent is responsible for its rapid onset of action. Because of the high plasma clearance (5.3 to 11.1 mg/kg/min) of rapacuronium, its clinical duration of action following single bolus doses up to 2 mg/kg in adults is short (i.e. <20 minutes). Rapacuronium forms a pharmacologically active 3-desacetyl metabolite, ORG-9488, which may contribute to a delay in spontaneous recovery after repeat bolus doses or infusions. After rapacuronium 1.5 mg/kg clinically acceptable intubating conditions are achieved within 60 to 90 seconds in the majority of adult and elderly patients undergoing elective anaesthesia. However, in a rapid-sequence setting. intubating conditions are less favourable after rapacuronium 1.5 to 2.5 mg/kg than after succinylcholine. The most prominent adverse effects of rapacuronium (tachycardia, hypotension and bronchospasm) are dose-related, and in particular pulmonary adverse effects are observed more frequently under conditions of a rapid-sequence induction in adults. Therefore, it seems worthwhile to consider only doses of rapacuronium < or = 1.5 mg/kg to facilitate rapid tracheal intubation, and to use succinylcholine or rocuronium rather than rapacuronium in a rapid-sequence setting. Rapacuronium, however, is a suitable alternative to mivacurium chloride (mivacurium) and succinylcholine for short procedures (e.g. ambulatory anaesthesia). Rocuronium bromide (rocuronium) is a relatively low-potent, intermediateacting NMBA. Its main advantage is the rapid onset of neuromuscular block whereby good or excellent intubating conditions are achieved within 60 to 90 seconds after rocuronium 0.6 mg/kg (2 x ED95), and within 60 to 180 seconds after smaller doses (1 to 1.5 x ED95). Larger doses of rocuronium (> or = 1 mg/kg) seem to be suitable for rapid-sequence induction under relatively light anaesthesia. However, it is still a matter of controversy whether, in the case of an unanticipated difficult intubation, the long duration of rocuronium administered in such large doses outweighs the many adverse effects of succinylcholine. Rocuronium has mild vagolytic effects and does not release histamine, even when administered in large doses. Rocuronium is primarily eliminated via the liver and its pharmacokinetic profile is similar to that of vecuronium bromide (vecuronium). Unlike vecuronium, rocuronium has no metabolite. Cisatracurium besilate (cisatracurium), the IR-cis, 1'R-cis isomer of atracurium besilate (atracurium) is approximately 4 times more potent than atracurium. The onset time of cisatracurium is significantly slower than after equipotent doses of atracurium. The recommended intubating dose is 0.15 to 0.2 mg/kg (3 to 4 times ED95). Over a wide range of clinically relevant doses the recovery properties of cisatracurium are affected by neither the size of the bolus dose nor by the duration of infusion. Unlike atracurium, cisatracurium does not trigger histamine release. Like atracurium, cisatracurium undergoes Hofmann elimination. In contrast to atracurium, cisatracurium does not undergo hydrolysis by nonspecific plasma esterases. Moreover, about 77% of the drug is cleared by organ-dependent mechanisms.

Adult↗

The effects of dexmedetomidine on neuromuscular blockade in human volunteers.

UNLABELLED: The neuromuscular effects of dexmedetomidine in humans are unknown. We evaluated the effect of dexmedetomidine on neuromuscular block and hemodynamics during propofol/alfentanil anesthesia. During propofol/alfentanil anesthesia, the rocuronium infusion rate was adjusted in 10 volunteers to maintain a stable first response (T1) in the train-of-four sequence at 50% +/- 3% of the pre-rocuronium value. Dexmedetomidine was then administered by computer-controlled infusion, targeting a plasma dexmedetomidine concentration of 0.6 ng/mL for 45 min. The evoked mechanical responses of the adductor pollicis responses (T1 response and T4/T1 ratio), systolic blood pressure (SBP), heart rate (HR), and transmitted light through a fingertip were measured during the dexmedetomidine infusion and compared with predexmedetomidine values using repeated-measures analysis of variance and Dunnett's test. Plasma dexmedetomidine levels ranged from 0.68 to 1.24 ng/mL. T1 values decreased during the infusion, from 51% +/- 2% to 44% +/- 9% (P < 0.0001). T4/T1 values did not change during the infusion. Plasma rocuronium concentrations increased during the infusion (P = 0.02). Dexmedetomidine increased SBP (P < 0.001) and decreased HR (P < 0.001) (5-min median values) during the infusion compared with values before the infusion. Dexmedetomidine increased the transmitted light through the fingertip by up to 41% +/- 8% during the dexmedetomidine infusion (P < 0.001).We demonstrated that dexmedetomidine (0.98 +/- 0.01 microg/kg) increased the plasma rocuronium concentration, decreased T1, increased SBP, and decreased finger blood flow during propofol/alfentanil anesthesia. We conclude that dexmedetomidine-induced vasoconstriction may alter the pharmacokinetics of rocuronium. IMPLICATIONS: We studied the effect of an alpha2-agonist (dexmedetomidine) on rocuronium-induced neuromuscular block during propofol/alfentanil anesthesia. We found that the rocuronium concentration increased and the T1 response decreased during the dexmedetomidine administration. Although these effects were statistically significant, it is unlikely that they are of clinical significance.

Adrenergic alpha-Agonists↗

Use of the intubating laryngeal mask airway: are muscle relaxants necessary?

BACKGROUND: The intubating laryngeal mask airway (ILMA) is designed to facilitate blind tracheal intubation. The effect of a muscle relaxant on the ability to perform tracheal intubation through the ILMA device has not been previously evaluated. This randomized, double-blind, placebo-controlled study was designed to evaluate rocuronium, 0.2 or 0.4 mg/kg administered intravenously, on the success rate and incidence of complications associated with ILMA-assisted tracheal intubation. METHODS: A total of 75 healthy patients were induced with propofol 2 mg/kg and fentanyl 1 microg/kg intravenously. After insertion of the ILMA device, patients were administered either saline, rocuronium 0.2 mg/kg, or rocuronium 0.4 mg/kg in a total volume of 5 ml. At 90 s after administration of the study drug, tracheal intubation was attempted using a disposable polyvinyl tube. If unsuccessful, a reusable silicone tube was tried. In addition to recording the time and number of attempts required to secure the airway, the incidence of complications during placement of the tracheal tube and removal of the ILMA were noted. RESULTS: Tracheal intubation was successful in 76-96% of the patients. The overall success rates and times required to secure the airway were similar in all three treatment groups. The high-dose rocuronium group experienced less patient movement (8 vs. 28 and 48%) and coughing (12 vs. 20 and 52%) than the low-dose rocuronium and saline groups, respectively. Use of rocuronium was also associated with a dose-related decrease in the requirement for supplemental bolus doses of propofol during intubation and removal of the ILMA device. CONCLUSIONS: Use of rocuronium did not significantly improve the success rate in performing tracheal intubation through the ILMA. However, it produced dose-related decreases in coughing and movement after tracheal intubation and reduced difficulties associated with removal of the ILMA device.

Adult↗

A priming technique accelerates onset of neuromuscular blockade at the laryngeal adductor muscles.

PURPOSE: Priming is a known technique to accelerate onset of neuromuscular blockade (NMB). Its effect on NMB of the larynx has not been studied yet. METHODS: We compared a priming technique with a bolus application of rocuronium on the onset of NMB at the laryngeal adductor and the adductor pollicis muscles (AP). In 30 female patients, after induction of anesthesia a tube with a surface electrode was placed into the trachea prior to the administration of any neuromuscular blocking agent to monitor electromyography (EMG) of the laryngeal adductor muscles. Neuromuscular monitoring consisted of EMG of the laryngeal adductor muscles and the left AP. Patients were randomized into two groups. After transcutaneous stimulation of the recurrent laryngeal nerve and ulnar nerve, a bolus of rocuronium 0.6 mg x kg(-1) (Bolus group) or a priming dose of rocuronium 0.06 mg x kg(-1) followed by rocuronium 0.54 mg x kg(-1) three minutes later (Priming group) were injected. Lag time, onset 90%, onset time and peak effect of NMB were recorded and compared; a P < 0.05 was considered significant. RESULTS: The onset 90% and onset time measured at the laryngeal adductor muscles (onset: 44.7 +/- 7.4 vs 74.0 +/- 23.8 sec) and at the AP (onset: 105.4 +/- 29.9 vs 139.2 +/- 51.5 sec) were significantly shorter in the Priming group than in the Bolus group. Within groups, the onset times were significantly shorter at the laryngeal muscles in comparison to AP. CONCLUSION: Our results indicate that a priming technique with rocuronium significantly accelerates the onset of NMB at the laryngeal adductor muscles. Our results further support the use of rocuronium as an alternative to succinylcholine for rapid sequence induction.

Adult↗

Interaction of neuromuscular blocking drugs with recombinant human m1-m5 muscarinic receptors expressed in Chinese hamster ovary cells.

1. Neuromuscular blocking drugs (NMBD's) are known to produce cardiovascular side effects manifesting as brady/tachycardias. In this study we have examined the interaction of a range of steroidal NMBD's with recombinant human m1-m5 muscarinic receptors expressed in Chinese hamster ovary cells. Our main hypothesis is that NMBD's may interact with m2 (cardiac) muscarinic receptors. 2. All binding studies were performed with cell membranes prepared from CHO m1-m5 cells in 1 ml volumes of 20 mM HEPES, 1 mM MgCl2 at pH 7.4 for 1 h. Muscarinic receptors were labelled with [3H]-NMS and displacement studies were performed with pancuronium, vecuronium, pipecuronium, rocuronium and gallamine. In addition a range of muscarinic receptor subtype selective reference compounds were included. In order to determine the nature of any interaction the effects of pancuronium, rocuronium and vecuronium on methacholine inhibition of forskolin stimulated cyclic AMP formation in CHO m2 cells was examined. Cyclic AMP formation was assessed in whole cells using a radioreceptor assay. All data are mean +/- s.e.mean (n > or = 5). 3. The binding of [3H]-NMS was dose-dependent and saturable in all cells tested. Bmax and Kd values in m1-m5 cells were 2242+/-75, 165+/-13, 1877+/-33, 458+/-30, 127+/-2 fmol mg(-1) protein and 0.11+/-0.02, 0.15+/-0.01, 0.12+/-0.01, 0.12+/-0.01, 0.22+/-0.01 nM respectively. 4. The binding of [3H]-NMS was displaced dose dependently (pK50) by pirenzepine in CHO m1 membranes (7.97+/-0.04), methoctramine in CHO m2 membranes (8.55+/-0.1), 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP) in CHO m3 membranes (9.38+/-0.03), tropicamide in CHO m4 membranes (6.98+/-0.01). 4-DAMP, pirenzepine, tropicamide and methoctramine displaced [3H]NMS in CHO m5 membranes with pK50 values of 9.20+/-0.14, 6.59+/-0.04, 6.89+/-0.05 and 7.22+/-0.01 respectively. These data confirm homogenous subtype expression in CHO m1-m5 cells. 5. [3H]NMS binding was displaced dose-dependently (pK50) by pancuronium (m1, 6.43+/-0.12; m2, 7.68+/-0.02; m3, 6.53+/-0.06; m4, 6.56+/-0.03; m5, 5.79+/-0.10), vecuronium (m1, 6.14+/-0.04; m2, 6.90+/-0.05; m3, 6.17+/-0.04; m4, 7.31+/-0.02; m5, 6.20+/-0.07), pipecuronium (m1, 6.34+/-0.11; m2, 6.58+/-0.03; m3, 5.94+/-0.01; m4, 6.60+/-0.06; m5, 4.80+/-0.03), rocuronium (m1, 5.42+/-0.01; m2, 5.40+/-0.02; m3, 4.34+/-0.02; m4, 5.02+/-0.04; m5, 5.10+/-0.03) and gallamine (m1, 6.83+/-0.05; m2, 7.67+/-0.04; m3, 6.06+/-0.06; m4, 6.20+/-0.03; m5, 5.34+/-0.03). 6. Cyclic AMP formation was inhibited dose dependently by methacholine in CHO m2 cells pEC50 for control and pancuronium (300 nM) treated cells were 6.18+/-0.34 and 3.57+/-0.36 respectively. Methacholine dose-response curves in the absence and presence of rocuronium (1 microM) and vecuronium (1 microM) did not differ significantly. Pancuronium, vecuronium and rocuronium did not inhibit cyclic AMP formation alone indicating no agonist activity. 7. With the exception of rocuronium there was a significant interaction with m2 muscarinic receptors with all NMBD's at clinically achievable concentrations suggesting that the brady/tachycardias associated with these agents may result from an interaction with cardiac muscarinic receptors. Furthermore pancuronium at clinically achievable concentrations antagonised methacholine inhibition of cyclic AMP formation in CHO m2 cells further suggesting that the tachycardia produced by this agent results from muscarinic antagonism. The mechanism of the bradycardia produced by vecuronium is unclear.

Analysis of Variance↗

[Rapid sequence induction in prehospital emergency medicine: is it safe?].

OBJECTIVE: The use of 0,9 mg/kg Rocuronium allows endotracheal intubation within 60 seconds and therefore might be an alternative to succinylcholine for rapid sequence induction. We investigated the use of high-dose Rocuronium for RSI in prehospital emergency medicine. METHODS: Rocuronium was used in two physician staffed units of emergency medical service for RSI in 79 patients aged 4 - 81 yrs (mean 46 yrs). Anesthesia was induced with etomidate/fentanyl or ketamine and 1 mg/kg of rocuronium. Recorded data were number of intubations, time interval application rocuronium-intubation, rating of intubation conditions and side effects. RESULTS: In 75 of 79 (94,9 %) patients intubation could be performed at the first attempt. In three (3,8 %) patients a second attempt and in one pt. a third attempt was necessary. In 78 (98,7 %) patients intubation could be performed within 60 seconds, in one patient intubation was completed within three minutes. The intubation conditions were estimated as excellent (n = 69; 87,3 %) or good (n = 10; 12,7 %) in all patients. No specific side effects could be observed. CONCLUSIONS: The use of muscle relaxants improves the intubation conditions and may help to avoid unnecessary high doses of anesthetics in hemodynamic unstable emergency patients. This study shows that rocuronium might be an alternative to succinylcholine for RSI also in prehospital emergency medicine, if succinylcholine is contraindicated.

Androstanols↗

The effect of rate of stimulation on force of contraction in a partially paralyzed rat phrenic nerve hemidiaphragm preparation.

This study was performed to determine whether presynaptic receptor blockade could be differentiated from postsynaptic blockade by examining the effect of increasing rates of indirect stimulation on twitch height depression (THD) on partially paralyzed in vitro rat diaphragm preparations. We calculated the T200/T1 ratio (force of the 200th stimuli divided by the force of the first stimuli) at rates of 0.2 Hz, 0.5 Hz, 1 Hz, and 2 Hz using a drug concentration which provided approximately 20% THD during stimulation at 0.1 Hz. Markedly different T200/T1 ratios were demonstrated when hexamethonium, a drug with predominantly presynaptic effects, was compared with alpha bungarotoxin, a drug with predominantly postsynaptic effects. These results were then compared with those from vecuronium, rocuronium, mivacurium, and tubocurarine. Both hexamethonium and rocuronium caused a marked decrease in T200/T1 ratio at higher rates of stimulation; alpha bungarotoxin caused a slight increase in T200/T1 ratio at higher rates of stimulation. The T200/T1 ratios produced by vecuronium, mivacurium, and tubocurarine lay intermediate between hexamethonium and alpha bungarotoxin. Significant differences in T200/T1 ratios were found when alpha bungarotoxin was compared with all other drugs at 2 Hz. Hexamethonium and rocuronium produced significant differences in T200/T1 ratio from those of all the other drugs at 1 Hz and 2 Hz. There were significant differences in the T200/T1 ratio found after hexamethonium and rocuronium compared to alpha bungarotoxin at 0.5 Hz. No significant differences at any rate of stimulation were found between hexamethonium and rocuronium. No difference was observed in the effect of vecuronium, mivacurium, and tubocurarine. We conclude that, if the observed effect is the result of hexamethonium acting predominantly at presynaptic sites and alpha bungarotoxin acting predominantly at postsynaptic sites, the relative contribution of small doses of nondepolarizing drugs at each site can be differentiated by determining the T200/T1 ratio at rates of 1 Hz or 2 Hz. Our results are consistent with the suggestion that small doses of rocuronium have marked presynaptic activity, but that vecuronium, mivacurium, and tubocurarine have both pre- and postsynaptic effects.

Androstanols↗

Variability of duration of action of neuromuscular-blocking drugs in elderly patients.

BACKGROUND: Steroid-based, non-depolarizing neuromuscular-blocking (NMB) drugs (e.g. rocuronium, vecuronium) are characterized by organ-dependent elimination and significantly longer durations of action in elderly compared to young patients. Cisatracurium is a benzylisoquinolinium NMB drug with a duration of action not altered by ageing. The objective of the study was to determine if elderly patients had less variability in duration of action with 2 x ED95 of cisatracurium compared to equipotent doses of rocuronium or vecuronium. METHODS: Informed consent was obtained from 66 elderly patients with normal renal and liver function. Preoperative midazolam (1 mg) was given IV. The anaesthestic induction was with 5 mg kg(-1) thiopental and 2 microg kg(-1) fentanyl. The patients received 0.6 mg kg(-1) rocuronium, 0.1 mg kg(-1) vecuronium or 0.1 mg kg(-1) cisatracurium. Anaesthetic maintenance was with sevoflurane in oxygen/nitrous oxide. Neuromuscular-blocking duration of action was defined as the return of T1 twitch height to 25% of control. Variability was determined by subtracting the actual duration of action from the mean duration of action for each drug. RESULTS: The durations of action (range, min) were: cisatracurium, 37-81; vecuronium, 35-137; and rocuronium, 33-119. The median of the variability of duration was significantly less with cisatracurium (7 min) compared to vecuronium (18 min) and rocuronium (18 min) (P < 0.05). CONCLUSION: When used with sevoflurane/N(2)O, there was a two-fold greater variability of duration of neuromuscular blockade in elderly patients receiving rocuronium or vecuronium compared with cisatracurium.

Aged↗

Selection of neuromuscular blocking agents in patients undergoing renal transplantation under general anesthesia.

OBJECTIVE: To study the pharmacodynamics of vecuronium,atracurium, mivacurium and rocuronium in patients with end-stage renal failure. METHODS: Forty-six patients with end-stage renal failure scheduled for renal transplantation and 53 patients with normal renal function were given either vecuronium, atracurium, mivacurium or rocuronium. The neuromuscular effects were monitored by the evoked response of the adductor pollicis to train-of-four stimulation of the ulnar nerve. RESULTS: Onset of vecuronium, atracurium and mivacurium occurred faster or tended to be faster in patients with end-stage renal failure, but there was no significant difference in onset by rocuronium between the control patients and renal failure patients. Furthermore, the no-response period, duration of action and recovery of atracurium did not differ between the two groups. There was no significant difference in duration of action or recovery of mivacurium between the two groups, whereas its no-response period was significantly prolonged in the patients with end-stage renal failure. There was no difference in no-response period or duration of action after the initial dose of vecuronium or rocuronium between the two groups. However, no-response period and duration of effect by vecuronium and rocuronium were prolonged with increasing incremental doses in patients with end-stage renal failure. CONCLUSIONS: All four muscle relaxants could be safely used in patients with end-stage renal failure. Onset of the relaxants were, in some cases, accelerated and no-response period of mivacurium was prolonged in patients with end-stage renal failure undergoing dialysis therapy. End-stage renal failure prolonged the no-response period and duration of action of vecuronium and rocuronium after repeated incremental doses, but did not alter those attributed to atracurium.

Adult↗

Implications of the use of neuromuscular transmission monitoring on immediate postoperative extubation in off-pump coronary artery bypass surgery.

BACKGROUND AND OBJECTIVE: When continuous infusions of neuromuscular blocking drugs are administered during lengthy interventions and no routine antagonism of their effects is applied, there is a dramatic incidence of residual curarization. We have examined whether the use of neuromuscular transmission monitoring results in differences in the incidence of postoperative residual curarization, the use of antagonist agents, and the endotracheal extubation rate and outcome after continuous infusion of rocuronium in patients undergoing off-pump coronary artery bypass surgery. METHODS: Twenty patients were assigned to group 1 (n = 10, non-blinded neuromuscular transmission monitoring) or group 2 (n = 10, blinded neuromuscular transmission monitoring). In group 1, patients were given rocuronium at an infusion rate of 6 microg kg(-1) min(-1). The rate was manually adjusted in order to maintain T1/T0 at 10%. In group 2, a rocuronium infusion was started 30 min after induction of anaesthesia, at a rate of 6 microg kg(-1) min(-1); this rate was left unchanged during surgery. The rocuronium infusion was discontinued on completion of all vascular anastomoses; propofol was stopped at the beginning of closure of the subcutis and pirinitramide (piritramide) 15 mg was administered intravenously. Remifentanil was discontinued at the beginning of skin closure and neostigmine (50 microg kg(-1)) administered at the end of surgery when the train-of-four ratio was < 0.9 in group 1, and routinely in group 2. A 20 min test period for spontaneous ventilation was allowed once surgery had been accomplished. When the train-of-four ratio was > or = 0.9 (group 1), patients were extubated if also breathing spontaneously, fully awake and able to follow commands. When they met the clinical criteria for normal neuromuscular function after induced blockade, patients in group 2 were extubated when fully awake and able to follow commands. RESULTS: In group 1, the rate of rocuronium infusion required to keep T1/T0 at 10% was 5 +/- 1.9 microg kg(-1) min(-1); this was not significantly different from the fixed rate in group 2 (P = 0.15). One patient in group 2 was excluded. Eight out of 10 and eight out of nine patients in groups 1 and 2, respectively, reached the extubation criteria. Three out of eight, and five out of eight, patients from groups 1 and 2, respectively, were extubated in the operating room. At that time of endotracheal extubation, all three patients from group 1, but only four of the five patients from group 2 had a train-of-four ratio > or = 0.9. In group 2, one patient was reintubated in the intensive care unit. The incidence of pharmacological reversal was high in group 1. CONCLUSIONS: Although we found no additional benefit of using neuromuscular transmission monitoring, it seems an absolute necessity for safety reasons. Pharmacological antagonism was mandatory. However, in our opinion, it is not wise routinely to perform immediate postoperative extubation in off-pump coronary artery bypass surgery.

Aged↗

[Muscle relaxants. New substances and neuromuscular monitoring].

INTRODUCTION: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards. MUSCLE RELAXANTS: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED95 of rocuronium provides good or excellent intubating conditions within 60 to 90 s. Slight vagolytic effects were reported following injection of 0.6 mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED95 did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid break-down by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.

Anesthesia↗

[Sugammadex (Org 25969, modified gamma-cyclodextrin)].

Sugammadex, a chemically modified gamma-cyclodextrin, was synthesized as a selective reversal agent for rocuronium, a steroidal neuromuscular blocking agent. The lipophilic cavity of sugammadex molecule encapsulates the lipophilic steroid rings of rocuronium and forms 1:1 host-guest complex. Additionally, negatively charged carboxyl groups around the rim of cyclic sugammadex easily attract a positively charged quaternary nitrogen of rocuronium. When sugammadex 8 mg x kg(-1) was given intravenously during a profound block induced by rocuronium, a train-of-four ratio of the thenar muscle to the ulnar nerve stimulation returned to 0.9 within 2 min. The rapid reversal can be explained by the rapid redistribution of free rocuronium from the neuromuscular junction to the plasma. The reversal effects are not influenced by anesthetics. There is no interaction with cholinergic systems. Therefore, undesired side effects attendant with anticholinesterases are not seen. No recurarization was also observed. The majority of the complexes is excreted via the kidney, but the reversal effects are complete even in patients with renal failure.

Cholinergic Antagonists↗

Hierarchical rule-based monitoring and fuzzy logic control for neuromuscular block.

OBJECTIVE: The important task for anaesthetists is to provide an adequate degree of neuromuscular block during surgical operations, so that it should not be difficult to antagonize at the end of surgery. Therefore, this study examined the application of a simple technique (i.e., fuzzy logic) to an almost ideal muscle relaxant (i.e., rocuronium) at general anaesthesia in order to control the system more easily, efficiently, intelligently and safely during an operation. METHODS: The characteristics of neuromuscular blockade induced by rocuronium were studied in 10 ASA I or II adult patients anaesthetized with inhalational (i.e., isoflurane) anaesthesia. A Datex Relaxograph was used to monitor neuromuscular block. And, ulnar nerve was stimulated supramaximally with repeated train-of-four via surface electrodes at the wrist. Initially a notebook personal computer was linked to a Datex Relaxograph to monitor electromyogram (EMG) signals which had been pruned by a three-level hierarchical structure of filters in order to design a controller for administering muscle relaxants. Furthermore, a four-level hierarchical fuzzy logic controller using the fuzzy logic and rule of thumb concept has been incorporated into the system. The Student's test was used to compare the variance between the groups. p < 0.05 was considered significant. RESULTS: The system achieved stable control of muscle relaxation with a mean T1% error of -0.19 (SD 0.66) % accommodating a range in mean infusion rate (MIR) of 0.21-0.49 mg x kg(-1) x h(-1). When these results were compared with our previous ones using the same hierarchical structure applied to mivacurium, less variation in the T1% error (p < 0.05) but the same variation in infusion rate were observed. The controller activity of these two drugs showed no significant difference (p > 0.5). However, the consistent medium coefficient variance (CV) of the MIR of both rocuronium (i.e., 36.13 (SD 9.35) %) and mivacurium (i.e., 34.03 (SD 10.76) %) indicated a good controller activity. CONCLUSIONS: The results showed that a hierarchical rule-based monitoring and fuzzy logic control architecture can provide stable control of neuromuscular block despite the considerable individual variation in neuromuscular block required among patients. Also, there was less variation in T1% error compared with that of previous study on mivacurium. Meanwhile, the consistent medium CV of the MIR of both rocuronium and mivacurium indicated a good controller activity which is able to withstand noise, diathermy effect, artifacts and surgical disturbances.

Adolescent↗