Time course and train-of-four fade of mivacurium block during sevoflurane and intravenous anaesthesia

BACKGROUND AND OBJECTIVE: Volatile anaesthetics inhibit nicotinic acetylcholine receptors at clinically relevant concentrations with higher affinity for the neuronal nicotinic receptor. The inhibitory effects of propofol on nicotinic receptors have only been documented at supraclinical concentrations. The aim of this study was to determine recovery properties and train-of-four (TOF) fade of mivacurium during sevoflurane and propofol anaesthesia, in order to examine any differences both in the enhancement of the neuromuscular block (postjunctional effects) and in TOF fade (prejunctional effects). METHODS: Twenty ASA I-II adult patients were randomly allocated to maintenance of anaesthesia with sevoflurane (end-tidal concentration 2%) or propofol. Neuromuscular block was assessed by acceleromyography and a single dose of mivacurium (0.15 mg kg(-1)) was administered (in the sevoflurane group after 30 min of exposure to sevoflurane). We measured time for recovery of the first twitch of the TOF (T1) from 25-75%, time from 25% recovery of T1 to achieving a TOF ratio (TOFR) of 0.8, TOFR at 50%, 75% and 90% recovery of T1, and height of T1 at TOFR of 0.7 and 0.9. Data were tested using t-test for independent samples. RESULTS: Recovery times (mean (95% confidence interval, CI)) of mivacurium in the sevoflurane group (T1 25-75%, 11.3 (8.1-14.5) min; T1 25%-TOFR0.8, 19.1 (15.7-22.5) min) were significantly longer (P < 0.05) than in the propofol group (T1 25-75%, 6.5 (5.2-7.7) min; T1 25%-TOFR0.8, 11.3 (7.8-10.3) min). No differences were found in the relations between TOFR and T1 or vice versa, between the groups. CONCLUSIONS: Recovery times after a single dose of mivacurium were prolonged by sevoflurane compared with propofol but no differences in TOF fade were observed between the two anaesthetics.     

Twitch augmentation and train-of-four fade during onset of neuromuscular block after subclinical doses of suxamethonium

We have studied the train-of-four (TOF) response mechanomyographically during onset of neuromuscular block produced by subclinical doses of suxamethonium in order to follow the augmentation of the first twitch of the TOF (T1) and TOF fade compared with control TOF responses before the drug was given. In the groups given suxamethonium 0.05, 0.1, 0.2 and 0.3 mg kg-1, the increments in T1 after administration of the drug were observed before twitch depression occurred; these were mean 22.3 (SEM 8.1)%, 19.2 (3.3)%, 10.8 (2.0)% and 4.2 (2.2)%, respectively. This effect was more marked with the lower doses (P < 0.05). The degree of TOF fade was moderate during onset of neuromuscular block and depended on the dose of drug. The results of this study suggest that low doses of suxamethonium produced transient increase in muscle tension and twitch depression with significant TOF fade. We conclude that suxamethonium was associated with presynaptic effects as a consequence of brief stimulation of acetylcholine release followed by progressive diminution at the neuromuscular junction.      

Effect of tetanic stimulation on subsequent train-of-four responses at various levels of vecuronium-induced neuromuscular block

Tetanic stimulation influences subsequent neuromuscular responses.In addition, the tetanus- induced changes in neuromuscular responsesdiffer according to the level of neuromuscular block at whichtetanic stimulation is delivered. We studied the tetanus-inducedeffect on subsequent train-of-four (TOF) responses at variouslevels of vecuronium-induced neuromuscular block in 45 anaesthetizedpatients. Tetanic stimulation was applied when a twitch heightof T1 returned to 25%, 50% and 75% of its control twitch height(T0) (groups 1, 2 and 3, respectively) after administrationof vecuronium 0.1 mg kg^–1. Maximum post-tetanic percentageincreases in TOF responses in groups 1, 2 and 3 were 257 (SD119)%, 107 (75)% and 68 (54)% for T1/T0 (P < 0.001 for group1 vs 2; P < 0.001 for group 1 vs 3) and 535 (259)%, 421 (213)%and 292 (171)% for T4/T1 (P < 0.01 for group 1 vs 3), respectively.Durations of post-tetanic increases in TOF responses in groups1, 2, and 3 were 52 (19)s, 37 (14)s, and 32 (13) s for T1/T0(P / 0.05 for group 1 vs 2; P < 0.01 for group 1 vs 3) and53 (17)s, 46 (15)s and 35 (12)s for T4/T1 (P < 0.05 for group1 vs 3), respectively. These data suggest that the tetanus-inducedeffect on subsequent TOF is more apparent and lasts longer atgreater degrees than at lesser degrees of neuromuscular block.     

Evolution of single twitch and train-of-four responses and of tetanic fade in relation to plasma concentrations of fazadinium in man

The evolution of single twitch and train-of-four (2 Hz) responses and tetanic fade (100 Hz) in relation to plasma concentration of fazadinium was determined during stable anesthesia (fentanyl-N2O) in six healthy adult patients after a bolus injection of 0.75 mg/kg of fazadinium. The interval between injection and 50% recovery and the corresponding fazadinium plasma concentrations were (mean +/- SEM): 47 +/- 4 minutes and 1.44 +/- 0.18 microgram/ml for the single twitch; 66 +/- 7 minutes and 1.01 +/- 0.10 microgram/ml for the train-of-four; and 83 +/- 11 minutes and 0.82 +/- 0.08 microgram/ml for tetanic fade. The results indicate that train-of-four and tetanic fade are more sensitive tests for evaluation of residual neuromuscular block than is measurement of single twitch responses.     

Tactile evaluation of fade of the train-of-four and double-burst stimulation using the anaesthetist's non-dominant hand

We have studied detection of fade in response to train-of-four (TOF), double-burst stimulation3,3 (DBS3,3) or DBS3,2, assessed tactilely by the anaesthetist using the index finger of the non-dominant hand and the thumb of the patient, compared with that assessed when the index finger of the dominant hand was used. The probability of detection of any fade in response to TOF or DBS3,3 using the non-dominant hand was significantly less than when the dominant hand was used (P < 0.05). The probability of identification of fade in response to DBS3,2 assessed using the non-dominant hand was comparable with that evaluated using the dominant hand when TOF ratios were 0-0.9, but when TOF ratios reached 0.91-1.00, detection using the non-dominant hand was significantly less common than with the dominant hand (12% vs 33%; P < 0.05). Using the non-dominant hand, the probability of detection of fade in response to ulnar nerve stimulation was less than that with the dominant hand and only the absence of DBS3,2 fade ensured sufficient recovery of neuromuscular block.      

Response to double-burst appears before response to train-of-four stimulation during recovery from non-depolarizing neuromuscular blockade

Background: Double-burst stimulation (DBS) it a relatively new nerve stimulation mode introduced for improved manual detection of residual neuromuscular blockade. Previous studies have shown that DBS_{3,3 50/50} (3 stimuli at 50 Hz followed 0.75 seconds later by 3 stimuli at 50 Hz) can detect deeper degrees of neuromuscular blockade than train-of-four (TOF) stimulation.
Aim: The aim of the present study was to examine if DBS_{3,3 80/40} (3 stimuli at 80 Hz followed 0.750 s later by 3 stimuli at 40 Hz) can detect even deeper degrees of neuromuscular blockade than DBS_{3,3 50/50} and to determine the time lapse from reappearance of response to each of the two DBS modes until reappearance of response to the TOF mode of nerve stimulation.
Methods: The study comprised 20 women undergoing gynaecological surgery and anaesthetised with fentanyl, thiopentone, halothane, and nitrous oxide. Neuromuscular transmission was monitored by using mechanomyography and stimulation of the ulnar nerve. Atracurium was used for neuromuscular blockade.
Results: Elapsed time from reappearance of response to DBS_{3,3 80/40} and DBS_{3,3 50/50} to reappearance of response to TOF stimulation was 459±196 (mean±SD) and 360±150 seconds, respectively, ( P <0.05).
Conclusions: DBS_{3,3 80/40} is capable of detecting deeper degrees of blockade than DBS_{3,3 50/50} which again is capable of detecting deeper degrees of blockade than TOF.     

Clinical assessment of the muscular response to tetanic nerve stimulation

The study was undertaken in order to determine clinical tactile evaluation of tetanic nerve stimulation (50 Hz, 5 sec) as a means of detecting fade and possible residual curarization. Forty-four patients were studied and 128 clinical evaluations by eight different observers were performed at various levels of neuro-muscular blockade. Tetanic fade was detected reliably by clinical evaluation only when high degrees of fade (tetanic fade ratio of 0.3 or less) were detected with a force-displacement transducer. We conclude that the clinical tactile assessment of the response to tetanic stimulation is not accurate except at very high degrees of fade and that its usefulness in monitoring neuromuscular recovery is doubtful.     

Visual evaluation of fade in response to facial nerve stimulation at the eyelid

STUDY OBJECTIVE: The aim of this study is to investigate the probability of visual detection of fade in response to train-of-four (TOF) stimulation, double-burst stimulation3,3 (DBS(3,3)), or DBS(3,2) at the eyelid in comparison to that at the thumb. DESIGN: This is a randomized single-blinded study. SETTING: The study took place at the University hospital. PATIENTS AND MEASUREMENTS: Sixty adult patients underwent general anesthesia. INTERVENTIONS AND MEASUREMENTS: Patients were randomly divided into either the eyelid group (n = 30) or the thumb group (n = 30). In the eyelid group, at the varying degrees of neuromuscular block caused by vecuronium, TOF, DBS(3,3), or DBS(3,2) were given at the temporal branch of the facial nerve, and the probability of visual detection of fade in response to TOF, DBS(3,3), or DBS(3,2) was determined at the eyelid. Similarly, in the thumb group, the probability of visual detection of fade in response to TOF, DBS(3,3), or DBS(3,2) was examined at the thumb. MAIN RESULTS: When the true TOF ratios were 0 to 0.60, the probability of detection of TOF fade in the eyelid group was significantly lower than in the thumb group (P < .05). At the true TOF ratios of 0.31 to 0.70, the probability of visual detection of DBS(3,3) fade in the eyelid group was significantly less than in the thumb group (P < .05). When the true TOF ratios were 0.81 to 1.00, the probability of detection of DBS(3,2) fade in the eyelid group was significantly higher than in the thumb group (P < .05). CONCLUSION: The probability of visual detection of fade in response to TOF or DBS(3,3) is lower at the eyelid than the thumb. In contrast, DBS(3,2) fade tends to be seen more frequently at the eyelid than at the thumb.     

Relationships between block-of-twitch and train-of-four fade in the mouse phrenic nerve-diaphragm preparation

The relationships between the block-of-twitch and train-of-four fade in the presence of nondepolarizing neuromuscular blocking drugs (d-tubocurarine, vecuronium and pancuronium) were examined in vitro by measuring the contractile tension from mouse phrenic nerve-diaphragm preparations. The slope of the block/fade relationship differed between onset of and recovery from neuromuscular block following single doses of d-tubocurarine, vecuronium or pancuronium. Decreasing the dose of d-tubocurarine or using a divided dose technique to accelerate onset (i.e., priming) increased the amount of fade for a given amount of block. In addition, the block/fade relationships for cumulative dosing and sequential dilution were the same when measurements were made at steady-state for several doses. It is concluded that the block/fade relationship in the mouse phrenic nerve-diaphragm preparation is variable, and is related to the time course of the neuromuscular block. In addition, the block/fade relationships for d-tubocurarine, vecuronium and pancuronium did not differ when determined at steady-state.     

Administration of sugammadex to a patient with myasthenia gravis with fade of the train-of-four ratio

A 50-year-old man (weight 87 kg, height 171 cm) with myasthenia gravis (MG) was scheduled for extended thymectomy under general anesthesia. His preanesthetic train-of-four ratio (T4/T1) was 59%. The first twitch of the train-of-four (T1) was 130% after calibration. We administered rocuronium 10 mg (0.11 mg x kg(-1)) for tracheal intubation. Maximal suppression was achieved in 50 seconds. During the operation, we did continuous infusion of rocuronium to maintain T1 at 10%. We discontinued rocuronium infusion before the end of surgery. In patients with MG, deep levels of neuromuscular block can be achieved with less rocuronium. We hypothesized that the requirement of sugammadex in a patient with MG is less than that in normal patients. Therefore, we administered 0.5 mg x kg(-1) of sugammadex. After 5 min, T4/T1 had reached 54%, but T1 had not reached the control value; therefore, we administered additional 1.5 m x kg(-1) of sugammadex. Subsequently, T1 reached 120%. Patients with MG with fade on T4/T1 require a full dose of sugammadex, identical to the dose administered to normal patients.     

Comparison of tactile and mechanomyo-graphical assessment of response to double burst and train-of-four stimulation during moderate and profound neuromuscular blockade

It is common clinical practice to estimate the degree of neuromuscular blockade by tactile evaluation of twitch responses. The aim of the present study was to evaluate the use of tactile responses of adductor pollicis to double-burst stimulation (DBS) and train-of-four (TOF) peripheral nerve stimulation for monitoring moderate and profound levels of neuromuscular blockade. The study comprised 44 women scheduled for gynaecological laparotomy and anaesthetised with midazolam, fentanyl, thiopentone, halothane, nitrous oxide and atracurium. The tactile responses of the adductor pollicis were compared with mechanomyographical measurements in the contra lateral arm during recovery from neuromuscular blockade. The observers (anaesthetic nurses) of the tactile responses were blinded with regard to the stimulation pattern and the mechanomyo-graphical measurements. The time from injection of the initial dose of atracurium until tactile reappearance of the first twitch in DBS (D₁), was 24.6 (0–39.8) min, median (range). This was more rapid than the time until tactile reappearance of the first twitch in TOF (T₁) 32.8 (18.–243.4) min (P< 0.05). The median time from tactile reappearance of D₁ until T₁ recovered to 15% of the control twitch height was longer than the median time from tactile reappearance of T₁ (14.6 versus 10.5 min) (P < 0.05). One or two responses to DBS or TOF were often felt before any responses had been detected mechanomyographically in the contralateral arm. When three or four responses to TOF were felt, responses were always detected mechanomyographically. It is concluded that tactile evaluation of responses to DBS stimulation can estimate deeper levels of blockade than tactile evaluation of responses to TOF.     

Subjective responses to train-of-four and double burst stimulation in awake patients

The present study was undertaken to determine whether the discomfort associated with the sequential bursts of stimuli comprising the two recommended forms of double burst stimulation (DBS) is comparable to that associated with the repetitive stimuli of train-of-four (TOF). Twenty-one unmedicated volunteers rated on a visual analog scale the discomfort associated with randomly applied DBS and TOF stimulations at 20, 30 and 50 mA. All participants were blinded to the mode of stimulation, as well as to the current intensity. At each amperage tested, TOF produced significantly less discomfort than either form of DBS (P less than 0.01). Stimulation at 50 mA produced median visual analog scale scores of 7.5, 7.0, and 5.0 for DBS3,2, DBS3,3, and TOF, respectively. At 30 mA the corresponding median visual analog scale scores were 4.5, 5.5, and 3.0, whereas at 20 mA the scores were 4.0, 4.5, and 2.0, respectively. Thus, DBS is more uncomfortable than TOF at each current tested; however, in light of reports of its higher sensitivity, DBS may be the preferred means of assessing neuromuscular function in the awake as well as the anesthetized patient when a force transducer and recorder are not readily available.     

Tactile fade detection with hand or wrist stimulation using train-of-four, double-burst stimulation, 50-hertz tetanus, 100-hertz tetanus, and acceleromyography

Residual neuromuscular blockade can be evaluated using acceleromyography, tactile assessment of train-of-four (TOF), double-burst stimulation (DBS), 50-Hz tetanus, or 100-Hz tetanus. Nerve stimulation can be at the hand or the wrist. We compared all these tests at both sites of stimulation. Rocuronium was given to 32 patients under sevoflurane anesthesia. The mechanomyographic adductor pollicis TOF ratio was measured at one extremity. In the other, stimulation was at the hand or the wrist, by random allocation, and the acceleromyographic TOF ratio was measured. During recovery, a blinded observer estimated tactile fade. The TOF fade became undetectable when mechanomyographic TOF ratio was (mean +/- sd) 0.31 +/- 0.15. For DBS, this threshold was 0.76 +/- 0.11. For 50-Hz tetanus, it was 0.31 +/- 0.15. For 100-Hz tetanus, it was 0.88 +/- 0.18, with a range of 0.14-1.00. These tactile responses were the same for hand and wrist stimulation. When acceleromyographic TOF ratio reached 1.0, the mechanomyographic TOF ratio was 0.89 +/- 0.06. With stimulation in the hand, acceleromyographic TOF ratio >1.0 was less frequent than at the wrist. To exclude residual paralysis, TOF, DBS, and 50-Hz tetanus are inadequate, 100-Hz tetanus is unreliable, and acceleromyography performs best.     

Acceleromyography vs. electromyography: an ipsilateral comparison of the indirectly evoked neuromuscular response to train-of-four stimulation

BACKGROUND: There is a considerable body of evidence which suggests that data obtained using acceleromyography (AMG) cannot be used interchangeably with observations obtained by mechanomyographic (MMG) or electromyograhic (EMG) methods. All previous such studies evaluated the responses from contralateral limbs. This investigation was undertaken to determine if these previously described differences were in part a function of observing the responses from opposing limbs. METHODS: We compared the ipsilateral EMG and AMG response to an ED(95) bolus of atracurium in 50 subjects. In half of the individuals the thumb was free to move freely; in half, a small elastic preload was applied to the thumb. Train-of-four (TOF) recovery was followed until a TOF ratio >0.90 was recorded by both monitors. Acceleromyography vs. EMG differences and the resultant 95% confidence limits for twitch height (T1) and the TOF ratio were determined. RESULTS: When the AMG TOF value had recovered to a value of 0.72 +/- 0.03; the simultaneously evoked EMG value averaged only 0.59 +/- 0.08. This difference was statistically significant (P < 0.001). Although the mean difference AMG vs. EMG was little more than 0.10, differences in an individual might be twice that amount. When the AMG TOF value had recovered to 0.90, the simultaneously evoked EMG value averaged 0.85. Again the 95% confidence limits for individual observations was very wide. With EMG, once the TOF ratio returns to a value of 0.70, T1 has returned to 95% of control. In contrast with AMG, return of T1 -95% of control requires a TOF ratio of almost 0.90. Addition of an elastic preload to the thumb decreased control TOF variability without effecting the relationship between twitch height and the TOF ratio. CONCLUSION: Acceleromyographic TOF values tend to overestimate the extent of EMG recovery. Acceleromyographic TOF values <0.90 are indicative of incomplete neuromuscular recovery.