A portable self-learning fuzzy logic control system for muscle relaxation

We have assessed the practicality and performance of the Vital Signs Paragraph neuromuscular blockade monitor as part of a 'self-learning' fuzzy logic control feedback system used to administer atracurium to a required depth of neuromuscular blockade. Fifteen patients undergoing surgery expected to last longer than 90 min entered the study. A Vital Signs Paragraph was used to measure the degree of neuromuscular blockade and control it such that the first twitch of the train-of-four was kept at 10% of its baseline value. The controller instructed a Graseby Medical 3400 infusion pump to administer an atracurium infusion to maintain this level of blockade. Five patients (33%) were withdrawn from the study due to inadequate piezo-electric sensor function. In the remaining 10 patients, the system achieved stable control of neuromuscular blockade with a mean (range) error for the first twitch of the train-of-four of −0.45 (−1.06 to 0.13)%. The mean atracurium infusion rate ranged from 0.13 to 0.67 mg.kg⁻¹.h⁻¹. These results compare reasonably well with previous results using the Datex Relaxograph, whilst the system itself was portable and easy to use. However, the reliability of the system was limited due to variability in the sensitivity of piezoelectric sensors.     

Closed-loop infusion of atracurium with four different anesthetic techniques

A new proportional-integral-derivative (PID) controller for the automated closed-loop delivery of atracurium was tested in 32 patients. Groups of 8 patients received halothane, enflurane, isoflurane, or N2O/morphine anesthesia. After induction of anesthesia with sodium thiopental 3-5 mg.kg-1, a bolus of atracurium 0.2 mg.kg-1 was delivered by the controller; this was followed by an infusion calculated by the controller to maintain the electromyogram (EMG) at a setpoint of 90% neuromuscular blockade. The average overshoot for the controller was 10.1% and the mean steady-state error 3.0%. The mean infusion rates for atracurium to maintain 90% blockade were calculated for each anesthetic group, with the inhalation anesthetics at 1 MAC. Infusion rates for N2O/morphine, halothane 0.8%, enflurane 1.7%, and isoflurane 1.4% at 90% blockade were 5.7 +/- 0.6, 4.9 +/- 0.3, 3.5 +/- 0.3, and 4.1 +/- 0.5 micrograms.kg-1.min-1, respectively (mean +/- SE). The infusion rate for atracurium at 90% blockade under N2O/morphine anesthesia was in general agreement with published values. The other infusion rates at 90% blockade have not been reported previously, but correspond to the known potencies of these inhalation anesthetics for augmentation of neuromuscular blockade. This controller performed well in comparison to previously developed controllers, and in addition was used as a research tool for rapid estimation of infusion rates.     

Performance assessment of a fuzzy controller for atracurium-induced neuromuscular block

The performance of a fuzzy controller for atracurium-induced neuromuscular block was assessed. Ten ASA I or II patients undergoing surgery anticipated to last at least 120 min were studied. A Datex Relaxograph was used to monitor neuromuscular block. Initially the T1 set point was set at 10% of baseline for at least 30 min (phase I). The T1 set point was then increased to 20% and then returned to 10% for two further periods of at least 30 min duration (phases II and III). The mean (SD) of the mean T1 error in 10 patients for phases I, II and III were 1.1 (1.4)%, -0.43 (1.2)% and 0.28 (0.94)%, respectively. The results show that a simple fuzzy logic controller can provide good accuracy with insensitivity to set point changes despite the considerable inter-individual variation in infusion rate required.      

Atracurium infusion during paediatric craniofacial surgery

A simple feedback control system was used to administer atracurium to 10 infants aged between 5 and 36 months during craniofacial reconstruction. The purpose of the study was to establish whether the system, previously evaluated only in adults, would be effective in paediatric patients. The individuals studied underwent long procedures with substantial blood loss and the potential for thermal and electrolyte disturbances. The system maintained the level of neuromuscular block successfully between 88 and 100% in all patients and between 90 and 100% in nine patients. The mean duration of feedback control was 179 (range 111-440) minutes. The mean (SD) dose of atracurium required was 0.40 (0.12) mg/kg/hour. The mean (SD) recovery time to a train-of-four ratio of 0.75 was 24.8 (9.9) minutes.     

AUTOMATIC CONTROL OF NEUROMUSCULAR BLOCK WITH ATRACURIUM

We have developed and tested a system for providing automaticcontrol of neuromuscular block with atracurium. The degree ofneuromuscular block was monitored in the small muscles of thehand using a Datex Relaxograph, and the signal was used as thecontrolled variable for a proportional plus integral controller.A preloaded integral was used to shorten the period of stabilization.The system was tested in 36 patients undergoing surgery andfound to produce stable block. For a target T1 of 20% of controlvalue, the mean block was 18.7 (SD 1.3) % of baseline T1 andthe mean consumption of atracurium was 5.39 (SD 1.23) µgkg^–1 min^–1. The block was sufficiently stable toact as a background for studies of pharmacological and physiologicalinteractions with atracurium.     

Model-based control of neuromuscular block using mivacurium: design and clinical verification

BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials. METHODS: Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated. RESULTS: Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.     

Model-based adaptive closed-loop feedback control of atracurium-induced neuromuscular blockade

Closed-loop control of atracurium-induced neuromuscular blockade by a model-based adaptive feedback algorithm is described. Mean offsets (+/- s.d.) from setpoints at 50, 70 and 90% neuromuscular blocks using the Relaxograph were 1.1 +/- 1.3, 0.2 +/- 0.7 and 0.1 +/- 0.4%, respectively. Correspondingly, the mean steady-state rates of infusion of atracurium were 0.20 +/- 0.06, 0.25 +/- 0.03 and 0.39 +/- 0.10 mg.kg-1.h-1. The described controller provides reasonable control of atracurium dosing at different degrees of neuromuscular blockade. It gives a solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.     

Atracurium infusion requirements in children during halothane, isoflurane, and narcotic anesthesia

We were interested in determining the dose-response relationship of atracurium in children (2-10 yr) during nitrous oxide-isoflurane anesthesia (1%) and the atracurium infusion rate required to maintain about 95% neuromuscular blockade during nitrous oxide-halothane (0.8%), nitrous oxide-isoflurane (1%), or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five children received 80, 100, 150 micrograms/kg atracurium, respectively. During isoflurane anesthesia, the neuromuscular block produced by 80 micrograms/kg was 23.6% +/- 6.5 (mean +/- SEM), by 100 micrograms/kg was 45% +/- 7.2, and by 150 micrograms/kg was 64% +/- 8.7. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 120 micrograms/kg and 280 micrograms/kg, respectively. At equipotent concentrations, halothane and isoflurane augment atracurium neuromuscular block to the same extent, compared to narcotic anesthesia. Atracurium steady-state infusion requirements averaged 6.3 +/- 0.6 micrograms . kg-1 . min-1 during halothane or isoflurane anesthesia; the requirements during balanced anesthesia were 9.3 +/- 0.8 micrograms . kg-1 . min-1 (P less than 0.05). There was no evidence of cumulation during prolonged atracurium infusion.     

Tactile evaluation of train-of-four count as an indicator of reliability of antagonism of vecuronium- or atracurium-induced neuromuscular blockade.

Recent evidence suggests that edrophonium is not the agent of choice to reverse profound neuromuscular blockade but remains an efficacious drug when the level of neuromuscular blockade to be antagonized is modest. We studied 90 healthy adults in an attempt to address the questions: 1) How much variability in such neuromuscular parameters as single twitch height and the train-of-four (TOF) fade ratio (T4/T1) exist when the TOF count first returns to four palpable responses? 2) Is edrophonium a reliable antagonist at this measured point of recovery? 3) What is the optimal dose of edrophonium needed to produce prompt (less than 10 min) and satisfactory (T4/T1 greater than 0.7) reversal when the fourth response of the thumb to indirect TOF stimulation just becomes palpable? Patients were given a bolus atracurium or vecuronium (n = 45 in each group) followed by an iv infusion sufficient to maintain single twitch as measured by electromyography at 10-15% of control values. At the end of surgery, the infusion was terminated and spontaneous recovery was allowed to begin. Once the tactile TOF count was four, edrophonium 0.3, 0.5, or 0.75 mg/kg was administered. At a count-of-four the first twitch averaged 37% of control (+/- 8.5% standard deviation; pooled data from all groups) and the mean T4/T1 ratio was 0.14 +/- 0.049. After atracurium neuromuscular blockade, edrophonium 0.3 mg/kg produced adequate antagonism in 10 min. At this time the mean T4/T1 ratio was 0.79 +/- 0.07 and the lowest observed value was 0.67. Increasing the edrophonium dose to 0.75 mg/kg accelerated recovery by 4-5 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of the interaction between atracurium and suxamethonium at 50% neuromuscular block using closed-loop feedback control of infusion of atracurium

We have studied the effect of prior administration of suxamethoniumon the infusion requirements of atracurium at 50% neuromuscularblock in patients undergoing elective general surgery. Anaesthesiawas maintained with nitrous oxide in oxygen, propofol and fentanyl.Of 20 patients given atracurium, only 10 were given prior administrationof suxamethonium 1 mg kg^–1. At the beginning of the infusion,atracurium 0.3 mg kg^–1 was given by bolus administration.Interaction between the two drugs was assessed by determiningthe steady state rate of infusion necessary to produce a constant50% neuromuscular block. This was accomplished by applying non-linearcurve fitting to data on the cumulative dose requirements duringanaesthesia. The neuromuscular blocking effect was found tobe similar with or without prior administration of suxamethonium.The mean steady-state rate of infusion for atracurium was 0.19(SD 0.03) mg kg^–1 h^–1 for patients given suxamethoniumand 0.18 (0.09) mg kg^–1 h^–1 for those who were notgiven suxamethonium. Thus prior administration of suxamethoniumdid not affect the infusion requirements of atracurium at 50%neuromuscular block, unlike the situation at constant 90% neuromuscularblock.     

Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients

BACKGROUND: The most sensitive diagnostic criterion of myasthenia gravis is a decrement in the muscular response to repetitive stimulation. The authors hypothesized that myasthenia gravis patients who show a train-of-four ratio (T4/T1) < 0.9 in the preanesthetic period will have increased sensitivity to nondepolarizing neuromuscular blocking agents compared with myasthenia gravis patients with preanesthetic T4/T1 > or = 0.9. METHODS: After institutional review board approval was obtained, 20 electrophysiologically documented myasthenia gravis patients were studied. Current pyridostigmine therapy was continued until the morning of surgery. Before induction of anesthesia, neuromuscular transmission was recorded from the hypothenar muscles using electromyography with train-of-four stimulation of the ulnar nerve. According to the T4/T1 ratio, patients were assigned to the "normal" group (T4/T1 > or = 0.9) or the "decrement" group (T4/T1 < 0.9). After induction of intravenous anesthesia, the effective dose to achieve a 95% neuromuscular blockade (ED95) for atracurium was assessed with a cumulative bolus technique. Postoperatively, pyridostigmine was titrated to obtain a T4/T1 > 0.75 and to treat residual myasthenic symptoms. RESULTS: In 14 patients, preanesthetic T4/T1 was > or = 0.9 (normal), whereas 6 patients presented with T4/T1 < 0.9 (decrement). Decrement patients had a lower ED95 of 0.07 +/- 0.03 mg/kg atracurium (mean +/- SD) compared with normal patients with an ED95 of 0.24 +/- 0.11 mg/kg atracurium (P = 0.002). All patients were extubated within 30 min after surgery. Postoperative pyridostigmine infusion did not differ significantly between groups. CONCLUSIONS: The requirement for atracurium is significantly reduced in myasthenia gravis patients with a T4/T1 ratio < 0.9 before anesthesia. This study indicates that routine neuromuscular monitoring in myasthenia gravis patients should be extended into the preinduction period to identify patients who require less atracurium.     

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.     

Preanesthetic Train-of-four Fade Predicts the Atracurium Requirement of Myasthenia Gravis Patients

Background: The most sensitive diagnostic criterion of myasthenia gravis is a decrement in the muscular response to repetitive stimulation. The authors hypothesized that myasthenia gravis patients who show a train-of-four ratio (T4/T1) < 0.9 in the preanesthetic period will have increased sensitivity to nondepolarizing neuromuscular blocking agents compared with myasthenia gravis patients with preanesthetic T4/T1 >= 0.9.

Methods: After institutional review board approval was obtained, 20 electrophysiologically documented myasthenia gravis patients were studied. Current pyridostigmine therapy was continued until the morning of surgery. Before induction of anesthesia, neuromuscular transmission was recorded from the hypothenar muscles using electromyography with train-of-four stimulation of the ulnar nerve. According to the T4/T1 ratio, patients were assigned to the "normal" group (T4/T1 >= 0.9) or the "decrement" group (T4/T1 < 0.9). After induction of intravenous anesthesia, the effective dose to achieve a 95% neuromuscular blockade (ED95) for atracurium was assessed with a cumulative bolus technique. Postoperatively, pyridostigmine was titrated to obtain a T4/T1 > 0.75 and to treat residual myasthenic symptoms.

Results: In 14 patients, preanesthetic T4/T1 was >= 0.9 (normal), whereas 6 patients presented with T4/T1 < 0.9 (decrement). Decrement patients had a lower ED95 of 0.07 +/- 0.03 mg/kg atracurium (mean +/- SD) compared with normal patients with an ED95 of 0.24 +/- 0.11 mg/kg atracurium (P = 0.002). All patients were extubated within 30 min after surgery. Postoperative pyridostigmine infusion did not differ significantly between groups.     

Quantifying the effect of enflurane on atracurium infusion requirements

The present study was designed to evaluate the interaction between atracurium and enflurane in 40 adult surgical patients using closed-loop feedback control of infusions of atracurium. Anaesthesia was induced with thiopentone and fentanyl and intubation was facilitated with atracurium 0.5 mg· kg^?1 lean body mass. During the first 90 min, anaesthesia was maintained with nitrous oxide in oxygen (2:1) and fentanyl. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: Group I, control, fentanyl-nitrous oxide anaesthesia; Group II, enflurane 0.3%-nitrous oxide; Group III, enflurane 0.6%-nitrous oxide; Group IV, enflurane 0.9%-nitrous oxide. The possible interaction of atracurium with enflurane was quantified by determining the asymptotic steady-state rate of infusion (I_ss) of atracurium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirements. Every patient served as his/her own control and the changes in the infusion rates were determined individually. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular blockade constant at the setpoint, did not differ among groups. In Group II I_ss decreased from 0.33 ± 0.12 to 0.26 ± 0.08 mg· kg^?1· hr^?1 (P < 0.01), in Group III from 0.32 ± to 0.12 to 0.24 ± 0.08 mg· kg^?1· hr^?1 (P < 0.001) and in Group IV from 0.29 ± 0.09 to 0.21 ± 0.09 mg· kg^?1 · hr^?1 (P < 0.001). In the control group atracurium requirements remained unchanged throughout the study. Enflurane reduces atracurium requirements in a dose-dependent manner. During enflurane anaesthesia the rate of atracurium infusion should be reduced but because of interindividual differences the monitoring of the neuromuscular function is important to ensure the appropriate level of neuromuscular block.     

Quantitation of the interaction between atracurium and succinylcholine using closed-loop feedback control of infusion of atracurium

The authors used closed-loop feedback control of infusion of atracurium to study the effect of prior administration of succinylcholine on neuromuscular blockade induced by atracurium in patients undergoing otolaryngologic surgery. Anesthesia was maintained with nitrous oxide in oxygen, flunitrazepam, and fentanyl. Of 14 patients given atracurium, seven were given prior administration of succinylcholine and seven were not. Interaction between the two drugs was quantified by determining the asymptotic steady-state rate of infusion necessary to produce a constant 90% neuromuscular blockade. This was accomplished by applying nonlinear curve-fitting to data on the cumulative dose requirement during anesthesia. The neuromuscular blocking effect of atracurium was found to be greater after prior administration of succinylcholine. The asymptotic steady-state rate of infusion (+/- SD) for atracurium was 0.27 +/- 0.06 mg.kg-1.h-1 for patients given succinylcholine and 0.38 +/- 0.10 mg.kg-1.h-1 for those not given succinylcholine. The clinical implication of this study is that the clinician should be aware of the fact that an induction dose of 1 mg/kg of succinylcholine does reduce atracurium requirement for 90% neuromuscular blockade by approximately 30%.     

Response to atracurium and mivacurium in a patient with Charcot-Marie-Tooth disease

Purpose

We studied the neuromuscular effects of both atracurium and mivacurium in a patient with Charcot-Marie-Tooth disease (CMTD) during nitrous oxide-oxygen-alfentanil-propofol anaesthesia. Neuromuscular blockade was monitored electromyographically. Train-of-four stimulation (2Hz @ 20 sec intervals) was delivered to the ulnar nerve throughout the period of observation.

Clinical features

A 17-yr-old man with the diagnosis of CMTD was presented twice for two different orthopaedic surgical procedures. The CMTD had been diagnosed since childhood. Neurological examination revealed distal wasting of the upper and lower limbs, generalised absence of reflexes and decreased sensation in a stocking distribution. In both anaesthetics, induction was carried out with alfentanil and propofol, and anaesthesia was maintained with nitrous oxide in oxygen, alfentanil and propofol infusion. The patient demonstrated a normal response to both atracurium and mivacurium. Onset time and the maximum block attained after atracurium and mivacurium were 240 and 210 sec, and 97% and 99% inhibition of T1 (the first twitch of TOF stimulation), respectively. Recovery of T1 to 10% of the control value occurred 30 and 11.5 min after the administration of atracurium and mivacurium, respectively. The patient made uneventful recoveries after both anaesthetics.

Conclusion

There was no evidence of prolonged response to atracurium and mivacurium in our patient with CMTD.     

The Maximum Depth of an Atracurium Neuromuscular Block Antagonized by Edrophonium to Effect Adequate Recovery

Background: The inability of edrophonium to rapidly reverse a deep nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling effect to antagonism of neuromuscular block by edrophonium. A ceiling effect means that only a certain level of neuromuscular block could be antagonized by edrophonium. Neuromuscular block greater than this could not be completely antagonized irrespective of the dose of edrophonium administered. The purpose of this study was to determine whether a ceiling effect occurred for antagonism of an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum level of block that could be antagonized by edrophonium.

Methods: In 30 adult patients, atracurium was administered to maintain a constant neuromuscular block. The level of block varied between patients. Evoked adductor pollicis twitch tension was monitored. Incremental doses of edrophonium were administered while the infusion of atracurium continued. Increments were given until adequate recovery occurred, as defined by a train-of-four (TOF) ratio greater or equal to 70%, or until no further antagonism of the block could be achieved. The probability of being able to effect adequate recovery by antagonism with edrophonium was determined using a logistic regression model. Cumulative dose-response curves were constructed using the logit transformation of the neuromuscular effect versus the logarithm of the cumulative dose of edrophonium.

Results: In 14 patients with a block of 25-77% depression of the first twitch response, antagonism by edrophonium to a TOF ratio greater or equal to 70% was possible, whereas in 16 patients with a 60-92% depression of T1, a TOF ratio > 70% was not achievable, indicating that a ceiling effect for antagonism by edrophonium occurred. A block of 67 plus/minus 3% (mean plus/minus SE) had a 50% probability of adequate antagonism. In patients in whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic effect occurred with an edrophonium dose of 0.8 plus/minus 0.33 mg *symbol* kg sup -1 (mean plus/minus SD).     

Experimental pharmacology of atracurium dibesylate

Atracurium dibesylate is a new non depolarizing muscle relaxant, metabolized by a non enzymic pathway, the Hofmann elimination. The potency of atracurium in animals was similar to d-tubocurarine and six times less than that of pancuronium. In the cat, the ED50 was 130 micrograms . kg-1; an intravenous dose of 250 micrograms . kg-1 atracurium was sufficient to cause complete neuromuscular block; its duration was 29 min. Single twitch block was readily antagonized by neostigmine 50-100 micrograms . kg-1 or edrophonium 200 micrograms . kg-1. Halothane potentiated the block given by atracurium. Dose ratio for 50% vagal block (ED50) and 50% neuromuscular block was 24; atracurium had weak ganglioplegic effects. 2,000 micrograms . kg-1 atracurium (eight times the neuromuscular blocking dose) reduced mean aortic pressure, heart rate, cardiac output and peripheral resistance. Such effects could be prevented by giving histamine receptor blockers prior to injecting atracurium.     

阿曲库铵气管插管肌松条件的研究

研究了肌松监测下河曲库铵气管插管的肌松条件。３２例患者随机分为三组。麻醉诱导：硫喷妥钠５～７ｍｇ／ｋｇ、阿曲库铵０．６ｍｇ／ｋｇ。根据肌松监测分别当Ｔ１＝２５％（组Ａ）、Ｔ１＝１０％（组Ｂ）、Ｔ１＝２％（组Ｃ）时气管插管。结果发现阿曲库铵首量后５．４分钟，Ｔ１＝２％时气管插管最为满意，随Ｔ１值的增加或给药后的时间缩短，插管的满意程度降低，尽管Ｔ１＝２５％时也可顺利气管插管，但插管的满意程度明显比Ｔ１＝２％时为差。三组气管插管后ＨＲ、ＭＡＰ均增加，但以组Ａ和组Ｂ增加明显，三组ＨＲ的增加幅度随Ｔ１值的增加而明显增加。     

Atracurium infusions in major ophthalmic surgery

Fifteen patients who were undergoing major ophthalmic surgery were anaesthetized using controlled ventilation with nitrous oxide, oxygen, midazolam and fentanyl after induction with thiopentone. Each was then given a bolus dose of 0.6 mg kg-1 atracurium followed immediately by an infusion of the drug at the rate of 0.6 mg kg-1 h-1, neuromuscular function being monitored throughout. Even slight movement can jeopardize the success of this type of surgery but good control of neuromuscular blockade was achieved without inhalational supplementation. The mean duration of the atracurium infusion was 118 min (range 30-247 min). The mean time from stopping the infusion to recovery of the first twitch of the train of four (TOF) to 20% was 25 min (range 11-44 min). Atropine (1.2 mg) and 5.0 mg neostigmine were then given in divided doses and a rapid and complete recovery was achieved. This technique can be used safely even in bad-risk patients but the infusion should be discontinued about 25 min before the end of surgery.