Mechanomyography (MMG) has, for many years, been regarded as the standard method for precise quantification of neuromuscular block (1). The conventional MMG measures the exact force of muscle contraction in response to electric stimulation of a motor nerve. It quantifies the neuromuscular function by measurement of the force displacement. However, the equipment is rather bulky, takes time to set up, and requires a rigid support of the arm in an often crowded operating room. All this limits its clinical use in daily anesthesia practice. However, the neuromuscular transmission module (M-NMT) is an integrated piezoelectric motion sensor module incorporated in the AS/3™ (Datex-Ohmeda, Helsinki, Finland) anesthesia monitor. The M-NMT quantifies neuromuscular function by measuring the signal generated from the bending and deformation of a piezoelectric sensor wafer strip as a result of thumb movement. Thus, the two monitors quantify the neuromuscular function on the basis of two different, but closely related, principles. The aim of the study was to compare the neuromuscular block of 0.6 mg/kg rocuronium (twice the 95% effective dose) monitored by the M-NMT with that by the Relaxometer® mechanomyograph (Groningen University, Groningen, Holland) (2).
A prospective, controlled, clinical, consecutive study was planned and conducted in accordance with the guidelines of “Good Clinical Research Practice (GCRP) in Pharmacodynamic Studies of Neuromuscular Blocking Agents”(1) and the consolidated standards of reporting trials statement (3). After approval of our institutional ethics committee, all patients who agreed to participate in the study gave their written informed consent. We excluded potential participants with a history of neuromuscular disease or small-joint arthritis and those who were receiving treatment with drugs thought to interfere with neuromuscular transmission. None of the female participants was pregnant or breast-feeding. Twenty consecutive patients aged 18–59 yr, ASA physical status I–II, undergoing short elective surgical procedures in the supine position which were expected to last for approximately 1 h, were included in the study.
Midazolam 7.5 mg orally was administered for premedication 1 h preoperatively. Anesthesia was induced with 2–4 mg/kg propofol until the eyelash reflex was obtunded. Anesthesia was maintained with 60% nitrous oxide in oxygen, 0.1–0.15 mg · kg−1 · min−1 propofol, and 0.1–0.2 μg · kg−1 · min−1 remifentanil infusions. Ventilation was adjusted to maintain end-tidal CO2 in the range of 35–40 mm Hg. Lactated Ringer’s solution was infused, through an IV catheter located on the arm, at a rate sufficient to replace fluid losses. Blood pressure was monitored noninvasively, once every 10 min, with the blood pressure cuff placed on the upper arm.
After induction, both arms were comfortably positioned on arm boards. The area above the ulnar nerve at the wrist, where the electrodes were to be placed, was cleaned to ensure adequate contact. To level out the effect of dominance of one hand, the two monitors were alternately allocated to the left or right hands. The force transducer of the Relaxometer (MMG) was attached to one hand, and the preload on the thumb was maintained within 200–400 g throughout the whole procedure. The M-NMT piezoelectric sensor was attached to the other hand for simultaneous monitoring. It consists of two quick-fit malleable plastic semicircular rings for the thumb and index finger with an interconnecting bending strip. The piezoelectric sensor pad, embedded in the bending strip, lies over the metacarpophalangeal joint of the thumb at the angle between the index finger and thumb. It is aligned with the ideal plane of the opposition movement of the thumb to the index finger. A narrow tape was used to fix the middle portion of the strip in place. This did not interfere with the thumb movement. The electrical wire was attached to the ring on the index finger, leaving the thumb free to move (Fig. 1).
In response to evoked stimulation of the ulnar nerve, the thumb movement resulted in bending and deformation of the piezoelectric sensor wafer. This generated a 200-ms positive voltage first and a negative voltage thereafter that was directly proportional to the thumb displacement. The area under the positive voltage wave curve over time was calculated and quantified. The signal was then filtered, amplified, displayed, and recorded.
After supramaximal current determination by both monitors, the ulnar nerves were stimulated via surface electrodes with 1-Hz single-twitch stimuli for 60 s (pulse width 200 μs, square wave), followed by train-of-four (TOF) stimuli (2 Hz, pulse width 200 μs, square wave for 2 s) at 12-s intervals. T1, the first twitch of the TOF expressed as a percentage of control response, and the TOF ratio (T4/T1) were used for evaluating the neuromuscular block. Artifact readings were filtered by discarding all measurements that suggested a change of more than 10% compared with the previous readings and those recorded during inflation of the arterial blood pressure cuff. Palmar skin temperatures of the thenar area of both hands, as well as core temperature, were monitored by the temperature probe of the MMG and the skin and esophageal probes of the AS/3. Patients were warmed (Bair Hugger™; Augustine Medical, Vienna, Austria) to keep the temperature of both hands constant at >32°C and the core temperature >35°C.
After a stable control response for both monitors was achieved, defined as variation of less than ±2% T1 for the last 3 min (1), 0.6 mg/kg rocuronium (twice the 95% effective dose) was administered. The trachea was intubated when T1 was maximally suppressed (4). Patients were allowed to recover spontaneously from the neuromuscular block. The MMG data were collected and stored with the AZG-Relaxometer 5.0 program (Groningen University) and the Datex-Ohmeda S/5 Collect (Datex-Ohmeda, Helsinki, Finland) data collection software for the M-NMT.
The time variables (min) included the following:
- 1. Stabilization period: from the start of monitoring until a stable control response was achieved.
- 2. Lag time: from the start of rocuronium administration until the first measurable effect of neuromuscular block.
- 3. Onset time: from the start of rocuronium administration until maximal T1 suppression.
- 4. Start of recovery: from the start of rocuronium administration until the first measurable effect of T1 recovery.
- 5. Dur10: from the start of rocuronium administration until 10% T1 recovery.
- 6. Dur25: from the start of rocuronium administration until 25% T1 recovery.
- 7. Dur0.8: from the start of rocuronium administration until 0.8 TOF ratio recovery.
- 8. Interval25–75: T1 recovery from 25% to 75%.
- 9. Interval10–90: T1 recovery from 10% to 90%.
- 10. Interval25–0.8: from 25% T1 until 0.8 TOF ratio recovery.
The paired Student’s t-test was used for the parametric data analysis. Data were expressed as mean ± sd. P < 0.05 was considered statistically significant. Data collected during recovery from neuromuscular block, as well as the pharmacodynamic variables, were analyzed on the basis of the statistical method of Bland and Altman (5). Although MMG might be regarded as the standard method for quantification of neuromuscular block (1), it is still subject to experimental error. The Bland and Altman analysis considers that both techniques are subject to experimental error and thus uses the average of the two measurements as an estimate of the true value rather than assuming that the MMG is a true standard. The bias defines the mean of the difference between the two monitors. The limits of agreement define the bias ± 1.96 sd in which 95% of the differences between the two monitors were expected to lie.
After the 60-s single-twitch stimulation, there was no difference in the stabilization period between the M-NMT (4.7 ± 1.5 min) and the MMG (4.9 ± 1.5 min). There was no difference in the prerelaxation TOF ratio monitored by the M-NMT (0.998 ± 0.02) compared with MMG (0.991 ± 0.018).
After rocuronium administration, the T1% and the TOF ratio of both monitors started to decrease simultaneously. There was no significant difference in the lag and onset times measured by the two monitors. Full block was reached in all patients independent of the monitoring technique.
Both monitors detected the start of recovery from neuromuscular block as well as 0.8 TOF ratio full recovery, with narrow limits of agreement. However, there was poor agreement between the two monitors in measuring Dur10 and Dur25, with the M-NMT on average underestimating the T1% measured by MMG (Table 1).
During recovery from neuromuscular block, the difference in T1% between the two monitors showed a bias of −15.9%. The limits of agreement were −40.8% and +8.9% (Fig. 2). The T1% regression plot showed a linear relationship between the two monitors (Fig. 3). The bias for the TOF ratio was −0.031, and the limits of agreement were −0.281 and +0.22 (Fig. 4). The regression plot demonstrated a close relationship between the two monitors at 0.8 TOF ratio full recovery (Fig. 5).
After full recovery from neuromuscular block, T1% monitored by MMG exceeded the control response (120.6 ± 12.8), which was significantly higher than T1% monitored by M-NMT (104.9 ± 16.9). This was not evident for the corresponding TOF ratios monitored by MMG (0.895 ± 0.08) or by M-NMT (0.915 ± 0.078).
The two monitors quantified the neuromuscular function on the basis of two closely related but different principles: namely, the force displacement of the thumb for the MMG and the motion of the thumb monitored by the piezoelectric (from Greek, meaning “pressure electric”) sensor of the M-NMT.
Reverse fade, in which T4 >T1 before the administration of neuromuscular blocking drugs, was reported in 50% of the patients monitored by the ParaGraph piezoelectric motion sensor (Vital Signs, Totowa, NJ) (6). Reverse fade was also reported with several piezoelectric acceleromyographic monitors (7–9). The TOF ratio monitored by the Acceleration transducer (Biometer, Copenhagen, Denmark) was constantly >1.0 even if monitoring continued for 20–60 minutes (7). The TOF ratio exceeded 1.0 in patients monitored by the Mini-Accelograph (Biometer) (8) and the TOF-Guard (Organon Teknika, Boxtel, Holland) (9). A possible explanation is that, despite the period of stabilization before neuromuscular blocking drug administration, the nonrelaxed free-moving thumb might not return to exactly the same position after each stimulus (9). Because the MMG applies a preload on the thumb, this might explain the absence of reverse fade demonstrated with the MMG in this study and in other studies (6–8). In contrast to all the previously mentioned piezoelectric motion sensor and acceleromyographic studies, the M-NMT manifested minimal reverse fade during the stabilization period. This could be due to its preadapted malleable bending strip, which allows the thumb to move freely only in one plane during stimulation and would bring the thumb back to almost the same position after each stimulus.
The authors of the previously mentioned studies could not exclude the reverse fade as a contributing factor in the subsequent difference, in their results, between the previously mentioned monitors and MMG (6–9). This is not the case with our results, because the MMG and M-NMT exhibited minimal reverse fade during the stabilization period.
The results of our study demonstrated that the two monitors simultaneously detected full neuromuscular block. This suggests that if tracheal intubation is attempted at full neuromuscular block (4), M-NMT is equally effective in indicating the time to tracheal intubation.
Discrepancies between the two monitors were minimal at the extremes of recovery from neuromuscular block, namely, at the start and at full recovery. However, along the course of recovery, the M-NMT reflected greater neuromuscular block than the MMG. This indicates that although the M-NMT is effective in identifying the full recovery from neuromuscular block, it lags behind the MMG in detecting the time to repeat rocuronium administration.
The mean 0.8 TOF ratio measured by the M-NMT in our study corresponded to the 0.798 TOF ratio when measured by the MMG (Fig. 5). Bland and Altman analysis demonstrated closer agreement (−0.062 and +0.118) between the two monitors at TOF ratio recovery of 0.8 (Fig. 4). This indicates that although the M-NMT could be overestimating the full recovery in some patients, the TOF ratio in this case would still be close to the 0.7 recovery threshold (10).
In this study we demonstrated that our TOF ratio limits of agreement are similar to those of other piezoelectric motion sensor monitors compared with MMG (6,10). The limits of agreement for the ParaGraph were −0.28 and +0.21 (6), and those for the piezoelectric sensor were −0.24 and +0.275 (10). This suggests that these discrepancies are largely due to an inherent difference in the fade characteristics between the two phenomena rather than the design of any of these monitors. These limits of agreement are still unacceptably wide to allow the values given by these monitors to be used interchangeably with MMG for individual patients.
Hand temperature <32°C could be a contributing factor in drift from baseline (T1 >100%) after full recovery from neuromuscular block (1). In addition, drift was suggested to be a consequence of the reverse fade manifested in the stabilization period (8). Although the hand temperature of all our study patients was kept constant at >34°C, and neither the MMG nor the M-NMT manifested significant reverse fade, our results revealed that MMG was still prone to drift. One possible explanation of this manifestation is that MMG requires frequent preload adjustments in response to even minor repositioning of the patient, to maintain it within 200–400 g. This might not necessarily bring the thumb back to the original prerelaxation position. The preadapted malleable bending strip of the M-NMT maintains the thumb in almost the same prerelaxation position; hence, the M-NMT was less prone to drift.
The consensus conference recommended the retrospective recalculation of all the MMG data recorded along the course of recovery from neuromuscular block according to the final T1% drift value (1). However, this was not the case in our study, because the purpose of our study was to compare the two monitors at various stages of neuromuscular block in the clinical daily anesthesia setting.
Among all the available neuromuscular monitors, the M-NMT offers the advantage of being incorporated into the anesthesia monitor, and thus it eliminates the need for an extra monitor in the often crowded operating room. The M-NMT monitor exhibited minimal reverse fade and minimal drift and could equally indicate the time to tracheal intubation and full recovery from neuromuscular block. It lagged behind the MMG in determining the time to rocuronium repeat dose administration. The M-NMT also has the advantage, in a busy operating room, of having a simple, small, quick-fit sensor that does not require time to set up or a rigid support of the arm. Thus, the M-NMT could be a reliable clinical monitor in daily anesthesia practice. However, the wide limits of agreement between the two monitors do not allow the values to be used interchangeably for individual patients.
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