Spontaneous Recovery Of Neuromuscular Function Research Articles

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.

An Ipsilateral Comparison of Acceleromyography and Electromyography During Recovery from Nondepolarizing Neuromuscular Block Under General Anesthesia in Humans

Residual neuromuscular block is defined as a mechanomyography (MMG) or electromyography (EMG) train-of-four (TOF) ratio <0.90, and is common in patients receiving neuromuscular blocking drugs. Objective neuromuscular monitoring is the only reliable way to detect and exclude residual neuromuscular block. Acceleromyography (AMG) is commercially available and easy to use in the clinical setting. However, AMG is not interchangeable with MMG or EMG. Currently, it is unclear what value must be reached by AMG TOF ratio to reliably exclude residual neuromuscular block. During spontaneous recovery from neuromuscular block, we monitored TOF ratio on the same arm using AMG at the adductor pollicis and EMG at the first dorsal interosseus. AMG and EMG TOF ratios were compared by the Bland-Altman analysis for repeated measurements. The precision of each device was assessed by the repeatability coefficient. A small repeatability coefficient indicates high precision of the device. The agreement between the devices was assessed by the bias and the 95% limits of agreement. Small bias and narrow limits of agreement indicate strong agreement. We defined clinically acceptable agreement between AMG and EMG as a bias <0.025 and limits of agreement within -0.050 to 0.050, provided that the control comparison between EMG and itself can fulfill these criteria. In 26 patients, 261 comparisons between AMG and EMG were made. The repeatability coefficient of AMG and EMG were 0.094 (95% confidence interval [CI], 0.088-0.100) and 0.051 (95% CI, 0.048-0.055), respectively. The bias between AMG and EMG TOF ratio was 0.176 (95% CI, 0.162-0.190), with limits of agreement -0.045 to 0.396 (95% CI, -0.067 to 0.419). AMG is less precise than EMG and overestimates EMG TOF ratio by at least 0.15. The lack of agreement cannot be attributed to instrumental imprecision or the baseline difference between successive measurements during spontaneous recovery of neuromuscular function. Residual neuromuscular block cannot be excluded on reaching an AMG TOF ratio of 1.00.

In Reply

The authors thank Drs. Fuchs-Buder and Schreiber for their interest in our clinical investigation,1and we welcome the opportunity to respond to the questions raised in their Letter to the Editor. We agree that the degree of spontaneous neuromuscular recovery at the time of neostigmine administration has an important effect on the incidence of residual paresis in the postanesthesia care unit. As demonstrated in the investigation of Kim et al. , the median (range) times required to achieve a train-of-four (TOF) ratio of 0.9 after reversal with neostigmine (0.07 mg/kg) were 22.6 (8.3–57.4) min at a TOF count of 2 and 9.7 (5.1–26.4) min at a TOF count of 4.2The relatively common practice of administering an anticholinesterase agent only a few minutes before tracheal extubation, regardless of the TOF count, likely explains the high incidence of residual neuromuscular blockade reported in numerous clinical investigations.3However, our data do not support the conclusion by Drs. Fuchs-Buder and Schreiber “that the difference in symptoms of muscle weakness and improved quality of recovery observed in this study could simply be the consequence of the dose or the timing of the administration of neostigmine.” In fact, no differences in management of reversal of neuromuscular blockade (time or dose) were observed between the acceleromyography and control groups. All patients in the study received a standard dose of neostigmine (50 μg/kg) “at the conclusion of the surgical closure.” The study protocol specifically defined the timing of neostigmine administration to standardize management in both groups and to account for the relatively long time required to achieve adequate recovery of neuromuscular function, even at a TOF count of 4 (10 min).3The protocol also stated that neostigmine should be given at a TOF count of 3–4 and this was achieved in the majority of patients because the median TOF count in both groups was 4 at reversal (only 1 patient of 150 had a TOF count of 0 at this time). Nonetheless, a higher percentage of patients in the acceleromyography group achieved spontaneous recovery to a TOF count of 4 at the time of reversal compared with our control group (80.3%vs. 55.4%, respectively). We believe this was due to more careful management of neuromuscular blockade at the end of surgery in the patients monitored with acceleromyography. In both study groups, dosing of neuromuscular blocking agents was carefully standardized; however, administration of additional neuromuscular blocking agents during the times of the operation not requiring neuromuscular blockade was at the discretion of the anesthesia care team. We hypothesized that acceleromyography monitoring would allow for more accurate titration of neuromuscular blocking agents during this important time period, and our findings supported this hypothesis (i.e. , fewer patients in the acceleromyography group received neuromuscular blocking agents during the last 45 min of the surgical procedure). Thus, our findings suggest that improved spontaneous recovery of neuromuscular function at the time of neostigmine administration in the acceleromyography group resulted in fewer patients with residual muscle weakness in the postanesthesia care unit.It should be noted that the protocol used a simple definition of the TOF count at the time of reversal. As indicated, neostigmine was administered when at least three to four visual responses (“twitches”) to TOF stimulation were observed. Data from the TOF-Watch SX®(Bluestar Enterprises, Omaha, NE) display were not used in the decision process at the time of reversal. We did not attempt to differentiate between a “strong fourth twitch” and a “weak fourth twitch.”In conclusion, we agree that improved spontaneous recovery at the time of reversal resulted in fewer symptoms of muscle weakness in the postanesthesia care unit. Our data suggest that acceleromyography monitoring, by allowing for more rational and accurate management of neuromuscular blockade, resulted in more patients with a TOF count of 4 at the time of reversal and fewer patients with residual paresis after tracheal extubation. Although additional analysis of our data could reveal that patients with higher TOF counts at the time of reversal have fewer symptoms of muscle weakness and improved quality of recovery, such an analysis is beyond the scope of a Letter to the Editor. Additional studies are needed to identify the mechanisms by which acceleromyography monitoring decreases the incidence of residual neuromuscular blockade.

The effects of age on maintenance of intense neuromuscular block with rocuronium

Increasing age is associated with a longer duration of action of neuromuscular block. The aim of this study was to determine the influence of ageing on the recovery of the post-tetanic count (PTC) from rocuronium-induced neuromuscular block. Twenty-two younger (20-60 years) and 22 older (> 70 years) patients were enrolled in this study. After induction of anaesthesia with fentanyl and propofol, all patients initially received 1 mg/kg rocuronium and neuromuscular block were evaluated by contractions of the adductor pollicis muscle to ulnar nerve train-of-four stimulation using an acceleromyograph. Subsequently, intense rocuronium-induced block was determined every 6 min using the PTC during 1.0-1.5% sevoflurane and remifentanil anaesthesia. When the first response to the PTC stimulus was detected, 0.2 mg/kg rocuronium was additionally administered, and again, spontaneous recovery of neuromuscular function was monitored until the first response to the PTC reappeared. Median values (range) of the times from the administration of 1 mg/kg and 0.2 mg/kg rocuronium until recovery of the first detectable PTC were significantly longer in the older [51.0 (27-100) min, P < 0.0001 and 30.0 (12-66) min, P = 0.0036, respectively] than the younger patients [31.5 (21-45) min and 18.0 (12-36) min, respectively]. The times from rocuronium injection to reappearance of the first response to PTC stimulation are approximately twofold longer and more variable in older than younger patients. Hence, the dosing interval of rocuronium should be adjusted using neuromuscular monitoring when maintaining intense neuromuscular block, especially in older patients.

Comparison of Cisatracurium and Vecuronium by Infusion in Neonates and Small Infants after Congenital Heart Surgery

Neonates and infants often require extended periods of mechanical ventilation facilitated by sedation and neuromuscular blockade. Twenty-three patients aged younger than 2 yr were randomly assigned to receive either cisatracurium or vecuronium infusions postoperatively in a double-blinded fashion after undergoing congenital heart surgery. The infusion was titrated to maintain one twitch of a train-of-four. The times to full spontaneous recovery of train-of-four without fade, extubation, intensive care unit discharge, and hospital discharge were documented after drug discontinuation. Sparse sampling after termination of the infusion and a one-compartment model were used for pharmacokinetic analysis. The Mann-Whitney U test and Student t test were used to compare data between groups. There were no significant differences between groups with respect to demographic data or duration of postoperative neuromuscular blockade infusion. The median recovery time for train-of-four for cisatracurium (30 min) was less than that for vecuronium (180 min) (P < 0.05). Three patients in the vecuronium group had prolonged train-of-four recovery: Two had long elimination half-lives for vecuronium, and one had a high concentration of 3-OH vecuronium. There were no differences in extubation times, intensive care unit stays, or hospital stays between groups. Our results parallel data from adults demonstrating a markedly shorter recovery of neuromuscular transmission after cisatracurium compared with vecuronium. Decreased clearance of vecuronium and the accumulation of 3-OH vecuronium may contribute to prolonged spontaneous recovery times. Cisatracurium is associated with faster spontaneous recovery of neuromuscular function compared with vecuronium but not with any differences in intermediate outcome measures in neonates and infants.

Cisatracurium during halothane and balanced anaesthesia in children

Cisatracurium, 51W89, is one of the ten stereoisomers of Tracrium which, unlike atracurium, has been reported to have a lack of histamine mediated cardiovascular effects at doses as high as 8 x ED95 in adults. We compared the time-course of neuromuscular effects of 80 micrograms.kg-1 or 100 micrograms.kg-1 cisatracurium during N2O-O2-halothane or N2O-O2-opioid anaesthesia, respectively, in 32 children 2-12 years old. Neuromuscular function was monitored by evoked adductor pollicis EMG. Even-numbered patients (n = 16) were allowed to obtain full spontaneous recovery of neuromuscular function and odd-numbered patients (n = 16) received neostigmine 45 micrograms.kg-1 together with glycopyrrolate at the time of 25% EMG recovery. Data are expressed as median with 10th to 90th percentile range. Cisatracurium had an onset time (time from administration to maximal effect) of 2.2 (1.7-3.8) or 2.3 (1.8-4.9) min, a clinical duration (time to 25% EMG recovery) of 34 (22-40) or 27 (24-33) min, and a spontaneous 25-75% recovery time (time from 25 to 75% EMG recovery) of 11 (9-13) or 11 (7-12) min during halothane or balanced anaesthesia, respectively (NS). Train-of-four ratio recovered to 0.70 in 2.5 (1.8-3.0) or 3.2 (2.1-4.3) min following neostigmine during halothane or balanced anaesthesia, respectively (NS). Changes in blood pressure or heart rate following cisatracurium were negligible. We regard cisatracurium as a safe and promising intermediate duration muscle relaxant the effects of which can easily be reversed with neostigmine.

The neuromuscular blocking effects of vecuronium during sevoflurane, halothane and balanced anaesthesia in children

Forty-five children aged 5-12 years were randomly allocated to receive 1.0 MAC of sevoflurane or halothane, or balanced anaesthesia with propofol and alfentanil. The ulnar nerve was stimulated every 20 s supramaximally with a train-of-four pattern and adductor pollicis electromyography was recorded. A cumulative log-probit dose-response curve of vecuronium was established. Thereafter, spontaneous recovery of neuromuscular function was monitored until complete. Effective doses of vecuronium were lowest in the sevoflurane group and greatest during balanced anaesthesia; for 50% neuromuscular blockade these were 13.3% micrograms.kg-1, 21.8 micrograms.kg-1 and 36.6 micrograms.kg-1 during sevoflurane, halothane and balanced anaesthesia, respectively, p < 0.05. Recovery of neuromuscular function was slower during sevoflurane than during halothane or balanced anaesthesia. Sevoflurane potentiated vecuronium more than halothane; when compared to balanced anaesthesia the dose requirements of vecuronium were reduced by approximately 60% and 40%, respectively.

Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children

The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1-12 yr. All received premedication with midazolam, 0.5 mg.kg-1 po and an inhalational induction with up to 3 MAC of either agent in 70% N2O and O2. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg.kg-1) iv. The onset of maximal blockade occurred in 2.4 +/- 1.26 (mean +/- SD) min with halothane and 1.8 +/- 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 +/- 2.6, 19.5 +/- 4.4, and 24.2 +/- 4.8 min) were greater than during halothane anaesthesia (7.2 +/- 2.2, 15.0 +/- 4.0, 19.2 +/- 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T1 > 95%, T4/T1 > 75%) during the surgery which lasted 24-63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary.

The isolated heart-lung preparation in the cat an in situ model to study the role of the lungs in the disposition of drugs

In the search for drugs with an extreme short time course of action, compunds should be developed that are rapidly distributed to and temporarily stored in well-perfused organs. Since the lungs receive the complete cardiac output and have the ability to temporarily store drugs, we have developed an in situ, isolated lung preparation in the cat to study the contribution of the lungs to the disposition of drugs. The cat's own heart perfuses the lung in situ with autologous blood. The circulation between the left ventricle and the right atrium is short-circuited via an aorta-caval shunt. The right forelimb is added to study pharmacodynamics simultaneously (only for muscle relaxants). Validation of the model for 180 min of perfusion showed complete isolation of the organs without major biochemical changes or edema and a stable muscle response. In pilot experiments with two structurally related muscle relaxants, initial muscle relaxation was followed by spontaneous recovery of neuromuscular function and a gradually decreasing plasma concentration, indicating partial disposition by the lungs. This was confirmed by direct concentration measurements in the lung. The present model may provide a powerful experimental tool to elucidate the role of the lungs in the disposition of drugs.

Spontaneous Recovery of Neuromuscular Function after Atracurium in Pediatric Patients

Spontaneous recovery of neuromuscular function after a bolus dose of 0.40 mg/kg atracurium was assessed in 60 newborn to adolescent patients during balanced anesthesia. Each patient was allowed to recover spontaneously until complete recovery of the single twitch (T1) response and the train-of-four ratio measured from the hypothenar muscle evoked compound EMG. The recovery times of T1 from the onset of relaxation to 10% recovery and to 100% recovery were significantly longer in patients under 10 kg of body weight than in the heavier patients (25 and 56 min vs 19 and 45 min, respectively, P less than 0.01). The rate of recovery, calculated as the recovery index (time between 25% recovery and 75% recovery of T1) was significantly longer in patients under 2 months of age than in older infants or children and adolescents. Atracurium remains, nevertheless, a relaxant of intermediate duration of action even in small infants.