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The study was conducted in two parts. First, evoked responses to common peroneal nerve stimulation at four electrode positions were tested in 25 awake volunteers. The initial threshold stimulus current (ITS) (minimal current producing dorsiflexion or eversion of the ankle joint and great toe) and the supramaximal stimulus current (SMS) (the point at which further increases in current did not produce increases in twitch tension) were defined. SMS was not reliably achieved using electrodes at each side of the fibular head. However, an exploratory electrode accurately located the nerve and enabled SMS in all volunteers (SMS/ITS = 3.4). Second, 16 anesthetized, paralyzed patients were studied. The common peroneal and ulnar nerves were stimulated simultaneously. Evoked tension was recorded at the adductor pollicis using a force transducer and at the great toe by a blinded observer. Reversal was given when the train-of-four count at the great toe reached four. Onset times were longer, and median posttetanic counts were greater, at the great toe compared with the adductor pollicis. Time from reversal to train-of-four ratio = 0.7 at the adductor pollicis was 207 ± 160 s. We conclude that neuromuscular monitoring at the common peroneal nerve was not equivalent to monitoring at the ulnar nerve. Implications: Accurate neuromuscular monitoring is important for patient safety. We studied the accuracy of monitoring at the common peroneal nerve in volunteers and patients. An exploratory electrode accurately located the common peroneal nerve. Monitoring at the common peroneal nerve was not equivalent to monitoring at the ulnar nerve in patients.
Neuromuscular monitoring enables accurate dosing and safe reversal of neuromuscular blockade (1). The common peroneal nerve has been suggested as a useful site for neuromuscular monitoring, particularly when the upper limb is inaccessible (2,3). The nerve is conveniently located at the lateral side of the leg and innervates the muscles of the anterior compartment of the leg that are responsible for dorsiflexion and eversion of the ankle and dorsiflexion of the great toe. However, common peroneal nerve stimulation has not been formally evaluated, nor has it been compared with the "gold standard," the ulnar nerve-adductor pollicis complex. Furthermore, common peroneal nerve monitoring may not be equivalent to monitoring other nerves in the leg. The posterior tibial nerve has been compared with the ulnar nerve, and significant differences have been reported (47). However, posterior nerve stimulation produces ankle and great toe plantar flexion, whereas common peroneal nerve stimulation produces ankle and great toe dorsiflexion. In addition, optimal electrode positioning and the feasibility of supramaximal stimulation (SMS) were not established for the posterior tibial nerve. Therefore, we sought optimal sites for nerve stimulation, assessed the feasibility of supramaximal nerve stimulation, and determined appropriate evoked muscular responses for monitoring in awake volunteers. We then compared the common peroneal nerve-great toe complex with the ulnar nerve-adductor pollicis complex during onset, maintenance, and reversal of neuromuscular blockade in anesthetized patients undergoing craniotomy.
Both studies were undertaken with approval from the Board of Medical Research of the hospital, and informed consent was obtained.
Volunteers Each volunteer rested on the laboratory bench with their left leg splinted to allow only ankle joint and toe movement. The force transducer was attached to the great toe, and preload was adjusted to approximately 300 g. The skin was shaved, cleaned with alcohol, and lightly abraded before Ag-AgCl electrodes were applied. Square-wave impulses of 0.2-ms duration were delivered by a Digistim III® nerve stimulator (Neuro Technology, Houston, TX). Evoked tension of ankle-joint movement was measured by using a linear force-displacement transducer and was continuously recorded on a polygraph. Four different electrode positions were studied for each volunteer (Figure 1): 1) posterior active: the active (negative) electrode was applied posterior to the fibula neck and the inactive (positive) electrode was applied anterior to the fibula neck; 2) anterior active: the active (negative) electrode was applied anterior to the fibula neck and the inactive (positive) electrode was applied posterior to the fibula neck; 3) exploratory: the active (negative) electrode was fixed after exploring around the neck of the fibula to find the point where the initial threshold stimulus current was least. The inactive (positive) electrode was applied just posterior to the biceps femoris tendon at the level of the knee joint; and 4) biceps tendon: the active (negative) electrode was applied immediately posterior to the biceps femoris tendon at the level of the knee joint. The inactive (positive) electrode was applied just proximal to the active electrode.
Nerve stimulation was performed at each electrode position. The initial threshold stimulus current (ITS) was defined by the minimal current producing visible dorsiflexion or eversion of the ankle joint and great toe. The stimulator output (single twitch, 0.1 Hz) was then increased in 2- to 5-mA increments until maximal current output was reached. Response curves for the four electrode positions were plotted for each volunteer. The SMS was defined by a blinded investigator as the point on each curve at which further increases in current did not produce significant increases in twitch tension. ITS and SMS currents at the four sites were compared using repeated-measures analysis of variance, with Sheffé's F-test. Linear regression with residual analysis was used to define the relationship between leg circumference and ITS or SMS current. Unpaired two-tailed t-tests were used to compare ITS current, tibial circumference, and %fat of volunteers in whom SMS was achieved compared with those in whom it was not achieved (posterior and anterior active groups only). ITS current was plotted against SMS current for each electrode position. A line was drawn from the origin with all points to the left of it. The gradient of this line represents the factor by which the ITS current must be multiplied to ensure SMS (8).
Patients Patients received temazepam 20 mg PO 1 h preoperatively and midazolam 15 mg IV during preparation. IV access and intraarterial blood pressure monitoring were established in the right arm. Routine monitors were applied. Anesthesia was induced with fentanyl 1.5 µg/kg and propofol 1.52.0 mg/kg and was maintained with a propofol infusion and intermittent boluses of fentanyl. Paralysis was induced with vecuronium 0.1 mg/kg, the trachea was intubated, and ventilation was commenced with 70% nitrous oxide and 30% oxygen. Paralysis was maintained with vecuronium by infusion to maintain a posttetanic count (PTC) of 17 at the adductor pollicis. At the end of surgery, neuromuscular blockade was reversed with neostigmine 0.05 mg/kg and atropine 0.025 mg/kg. Core temperature was measured in the distal esophagus and maintained above 35.5°C using a forced air warmer (9). Forearm minus fingertip skin temperature gradients were measured on the left arm, and thermoregulatory vasoconstriction was identified by a gradient >0°C (10). This arm was shielded from heating devices. Neuromuscular blockade was assessed in the left upper and lower limbs. The skin was prepared, and nerve stimulation was delivered as previously described. The ulnar nerve was located lateral to the tendon of flexor carpi ulnaris at the proximal skin crease of the wrist (11). Evoked tension at the adductor pollicis was determined using a force transducer, as described. For common peroneal nerve stimulation, the exploratory electrode position was used. A response after common peroneal nerve stimulation was defined as obvious palpable dorsiflexion of the great toe and was counted and recorded by a blinded observer. Anesthesia was induced and train-of-four (TOF) stimulation was commenced at both sites at 3.5 times the ITS current. Once twitch height stabilized, neuromuscular blockade was induced, and the time to disappearance of the first twitch at each site was recorded as the onset time. During surgery, PTCs were recorded simultaneously at both sites every 6 min. During recovery from neuromuscular blockade, TOF counts (TOFCs) were measured every 10 s. Neostigmine and atropine were given when the TOFC reached 4 at the great toe: the time from this point to a TOF ratio (TOFR) = 0.7 at the adductor pollicis was measured and defined as reversal time. Paired two-tailed t-tests were used to compare onset times and reversal times. A Mann-Whitney U-test was used to compare median PTCs. Spearman rank order correlations were used to correlate the height of the first twitch in the TOF compared with control (T1%) at the adductor pollicis, and the TOFC at the adductor pollicis, with the TOFC at the great toe. A Bland-Altman analysis was used to assess the relationship between the TOFC at the adductor pollicis and the great toe (12). Data are presented as mean ± SD; P < 0.05 was considered statistically significant.
Volunteers SMS currents were identified by obvious plateaus in the response curves when the exploratory and biceps tendon electrode positions were used. In contrast, many response curves from posterior and anterior active positions had no identifiable plateau (Figure 2).
ITS currents for exploratory and biceps tendon electrode positions were significantly less than those for posterior and anterior active positions. SMS was universally achieved using the exploratory and biceps tendon positions, and multiplying the initial threshold stimulus current by 3.4 and 3.5, respectively, ensured SMS in all volunteers (Figure 3, Table 1 ).
SMS was not achieved in all volunteers when posterior or anterior active electrode positions were used; therefore, a reliable relationship between the ITS and SMS currents was not defined. Volunteers in whom SMS was not achieved in the posterior active position had significantly greater ITS currents (22 ± 5 vs 15 ± 4 mA) and tibial circumferences (38 ± 2 vs 35 ± 1 cm) than those in whom SMS was achieved. However, neither of these factors correlated with SMS current in the anterior active group. Linear regression analysis revealed that tibial circumference was not related to SMS current in any electrode position (Table 2).
Patients Onset of neuromuscular block was slower at the great toe than at the adductor pollicis (179 ± 82 vs 151 ± 54 s; P = 0.015). During maintenance, the median PTC was significantly greater at the great toe than at the adductor pollicis (8 vs 4; P = 0.0001) (Figure 4).
During spontaneous recovery from neuromuscular blockade, there was correlation between T1% at the adductor pollicis and TOFCs at the great toe (r = 0.74; P < 0.05) and between TOFCs at the adductor pollicis and TOFCs at the great toe (r = 0.72; P < 0.05). T1% was 3% ± 3%, 18% ± 12%, 24% ± 14%, and 35% ± 16% when the first, second, third, and fourth twitches reappeared at the great toe. When the TOFC = 1 at the great toe, the TOFC at the adductor pollicis was 0 in 4 patients and 1 in 12 patients. When the TOFC = 4 at the great toe, the TOFC at the adductor pollicis was 1 in two patients, 2 in five patients, 3 in two patients, and 4 in seven patients. On the Bland-Altman plot, the mean of the differences between the TOFCs at the adductor pollicis and great toe was 0.61 ± 0.88, and the limits of agreement were -1.12 to 2.34. Neuromuscular blockade was reversed when the TOFC reached 4 at the great toe. Mean reversal time was 207 ± 160 s (range 50570 s). If the TOFC at the adductor pollicis was <4 at reversal, reversal time was 304 ± 176 s. In contrast, if the TOFC at the adductor pollicis was equal to 4, then the reversal time was 110 ± 48 s (P < 0.03). Forearm minus fingertip skin temperature gradients remained < 0°C in all patients.
This study demonstrates that optimal positioning of electrodes is essential for accurate neuromuscular monitoring at the common peroneal nerve. In addition, there are some important differences between neuromuscular monitoring at the great toe and the adductor pollicis that must be borne in mind when this site is used for clinical neuromuscular monitoring. An exploratory electrode accurately located the common peroneal nerve and ensured reliable results. Positioning the electrodes over the biceps tendon also was reliable because the tendon is a readily palpable landmark, even in obese subjects, and the nerve is superficial at this point. However, positioning the electrodes at either side of the neck of the fibula failed to provide reliable results. In larger individuals, the neck of the fibula is not easy to locate, and when overlying tissues are thick, the currents required for stimulation are greater, exceeding maximal stimulator output in some instances. Positioning the electrodes at either side of the fibula neck is only acceptable if a low ITS current indicates that the nerve has been accurately located. An additional problem resulting from positioning the electrodes at either side of the neck of the fibula relates to the division of the nerve at this point into superficial and deep peroneal branches. The active electrode may stimulate the superficial and deep branches separately; because branches lie at different distances from the surface, each will have a different ITS and SMS. A plot of the response to stimulation will be a confusing composite of the two branches and is unlikely to feature the plateau in the response curve that normally defines SMS. Electrode polarity may affect nerve stimulation (13,14). When stimulating the common peroneal nerve with the active electrode anterior to the neck of the fibula, the inactive electrode (anode) is positioned closest to the nerve. Failure to achieve SMS in our study may have been due to anodal stimulation, which required currents greater than the maximal output of the nerve stimulator. Anodal stimulation, however, may not be clinically important (15). Accurate neuromuscular monitoring requires SMS (11,13,16,17). When the exploratory or the biceps tendon electrode positions were used to stimulate the common peroneal nerve, delivering 3.5 times the initial threshold stimulus current was predicted to produce SMS. In contrast, a ratio of 2.75 was reported for the ulnar nerve at the wrist (8). The difference between these two results may be explained by the greater diameter of the common peroneal nerve or greater distance from the skin to the nerve. However, this ratio still allows SMS in all subjects using available nerve stimulators (11). Several evoked muscular responses resulted from common peroneal nerve stimulation around the knee joint. Ankle eversion resulted from the contraction of peroneus longus and brevis and may have resulted, in part, from direct muscle stimulation. Common peroneal nerve stimulation resulted in strong ankle dorsiflexion, but we found that ankle eversion interfered with the detection of ankle dorsiflexion. Great toe dorsiflexion resulted from contraction of extensor hallucis longus and extensor hallucis brevis. We recommend monitoring great toe dorsiflexion because it was the easiest to assess and least likely to be interfered with by direct muscle stimulation. Before the muscles innervated by the common peroneal nerve can be used to monitor neuromuscular blockade in patients, we must know how they compare with the adductor pollicis (the gold standard). Other monitoring sites have differed from adductor pollicis in terms of time course of block and sensitivity (18). Therefore, we compared the common peroneal nerve-great toe complex with the ulnar nerve-adductor pollicis complex. The common peroneal nerve-great toe complex behaved similarly to the tibial nerve-great toe complex during neuromuscular blockade (4,6,7). For example, Kitajima et al. (6) investigated the plantar evoked response of the great toe after tibial nerve stimulation behind the ankle using acceleromyography and showed that onset was slower, recovery was faster, and depth of neuromuscular blockade was less at the great toe than at the adductor pollicis. These results show that both nerve-muscle groups act on the same joint and probably have similar blood flow and muscle fiber composition (19). Onset of neuromuscular blockade at the great toe was slower than that at the adductor pollicis. Muscle blood flow is the most important factor affecting onset of neuromuscular blockade (20). For example, the faster onset time of the diaphragm compared with the adductor pollicis is attributed to differences in blood flow (21,22). We postulate that faster onset of blockade at the adductor pollicis is due to greater blood flow to this muscle compared with the great toe dorsiflexors. During maintenance of neuromuscular blockade, the great toe dorsiflexors were more resistant to neuromuscular blockade than the adductor pollicis. Differences in the sensitivity of muscles to muscle relaxants may be attributed to muscle composition (23). Muscles composed of fast twitch fibers, such as the adductor pollicis, are more sensitive than those predominantly composed of slow fibers, such as the diaphragm (24). The dorsiflexors of the great toe contain a significant proportion of slow fibers, which allows these muscles to perform the prolonged contractions required to maintain posture and balance (19). Therefore, like the diaphragm, the dorsiflexors of the great toe should be more resistant to neuromuscular blockade than the adductor pollicis (18,25). Recovery is also related to muscle sensitivity: more resistant muscles recover earlier than more sensitive ones (22). In all our patients, the fourth twitch on the TOFC appeared at the great toe before the it appeared at the adductor pollicis. However, all patients achieved a TOFR = 0.7 at the adductor pollicis <10 min after reversal, which is within the accepted levels of safety because the peak effect of antagonism by neostigmine occurs between 7 and 11 min (26). In this study, we wanted to validate clinical monitoring of the common peroneal nerve-great toe complex. Mechanomyography was used at the adductor pollicis because this is the known reference measure. Using this method, we compared clinical end points, such as the TOFC and PTC, at the great toe, as assessed by a single observer. Our results can therefore be applied in the clinical setting without expensive monitoring equipment. We chose tactile, rather than visual, assessment of evoked responses at the great toe. Visual assessment leads to underestimation of the depth of neuromuscular blockade because very small responses that result from direct muscle stimulation or repetitive nerve firing may be included (27). Tactile evaluation may produce better results because applying preload to the muscle maximizes its contraction (28). We routinely count obvious muscular responses. In this way, we believe that the threshold for defining a response will be very similar to mechanomyography. We did not attempt to detect the TOFR manually during recovery, as manually or visually detecting fade is notoriously inaccurate (29). Instead, we restricted our clinical assessment to twitch counts: both the TOFC and PTC are sufficiently accurate when measured clinically (30,31). In conclusion, we recommend monitoring behind the biceps tendon or using an exploratory electrode at the neck of the fibula. At either of these positions, stimulation with 3.5 times the ITS will achieve SMS in all subjects. Onset of blockade at the great toe is slower than that at the adductor pollicis. There is relative resistance to neuromuscular blockade at the great toe. A greater PTC can be accepted during maintenance than if the adductor pollicis is used for monitoring. Reversal of vecuronium neuromuscular blockade with neostigmine can be undertaken safely when four twitches have returned on the TOFC at the great toe.
We thank our volunteers from the Department of Anesthesia, Royal Melbourne Hospital, and the physicians of the Department of Neurosurgery, Royal Melbourne Hospital, for allowing us to study their patients. We gratefully acknowledge the statistical advice of Dr. Paul Myles.
Presented in part at the combined annual scientific meeting of the Australian and New Zealand College of Anaesthetists and the Australian Society of Anaesthetists, Perth, Australia, October 1996; and at the annual scientific meeting of the Australian and New Zealand College of Anaesthetists, Christchurch, New Zealand, May 1997.
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