U ploD ate’ Mfficial reprint from UpToDate? www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. 8. Wolters Kluwer Monitoring neuromuscular blockade Author: Johnathan Ross Renew, MD Section Editor: Girish P Joshi, MB, BS, MD, FFARCSI Deputy Editor: Marianna Crowley, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Dec 2022. | This topic last updated: Jan 13, 2023. INTRODUCTION Neuromuscular blocking agents (NMBAs) are usually administered during anesthesia to facilitate endotracheal intubation and/or to improve surgical conditions. Neuromuscular block should be monitored for all patients who receive NMBAs during anesthesia, to guide dosing of NMBAs and reversal agents, and to assess the degree of recovery. This topic will discuss the devices that may be used, the patterns of nerve stimulation, and interpretation of results. The choice of NMBAs, clinical uses for anesthesia, and reversal of neuromuscular block are discussed separately. (See "Clinical use of neuromuscular blocking agents in anesthesia".) WHEN AND HOW TO MONITOR NEUROMUSCULAR BLOCKADE We suggest the use of quantitative, objective measurement of neuromuscular function (ie, accelerometry, electromyography [EMG], kinemyography [KMG]) to monitor administration of and recovery from neuromuscular blocking agents (NMBAs) whenever possible. If a quantitative monitor is not available, qualitative monitoring with a peripheral nerve stimulator may be used, but only to determine the depth of block (train-of-four count [TOFC)). Evaluations of train-of-four (TOF) fade made subjectively (with a peripheral nerve stimulator) cannot assure adequate recovery. (See ‘Qualitative versus quantitative monitoring’ below.) In 2023, both the American Society of Anesthesiologists (ASA) and European Society of Anaesthesiology and Intensive Care (ESAIC) published guidelines on the management of neuromuscular blockade [1,2]. Both societies strongly recommend the use of objective monitors whenever NMBAs are administered. These recommendations align with aconsensus statement issued in 2018 by an international panel of experts in neuromuscular blockade [3], which state that objective monitoring (documentation of TOF ratio [TOFR] 20.9) is the only method of assuring satisfactory recovery of neuromuscular function, and if a quantitative monitor is not available, the use of a peripheral nerve stimulator is mandatory when NMBAs are used. Previously, a 2020 guideline for the use of NMBAs from the French anesthesia society recommended monitoring whenever NMBAs are used [4], and the 2021 guidelines for monitoring standards from the Association of Anesthetists of Great Britain and Ireland (AAGBI) states that quantitative neuromuscular monitoring should be used whenever NMBAs are administered for anesthesia [5]. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on ‘Avoidance of residual neuromuscular blockade'.) However, in a large 2010 survey of anesthesia providers, 19.3 percent of Europeans and 9.4 percent of Americans never use neuromuscular monitors [6]. In a 2017 survey of anesthesia clinicians in Denmark, objective neuromuscular monitors were always used by 60 percent of clinicians when NMBAs were administered [7]. CLINICAL EVALUATION Clinical tests that have historically been used to assess recovery from neuromuscular blockade (ie, grip strength, vital capacity, head lift) are not sensitive or specific for detection of residual weakness [8-12]. Reliance on clinical evaluation alone to manage neuromuscular blocking agent (NMBA) administration can result in residual paralysis. (See "Clinical use of neuromuscular blocking agents in anesthesia’, section on ‘Avoidance of residual neuromuscular blockade’.) PERIPHERAL NERVE STIMULATION Monitors of neuromuscular function use stimulation of a peripheral nerve, and evaluation of a response (ie, a contraction or twitch) in the innervated muscle. The peripheral nerve stimulator consists of a battery powered device that may be portable or hand held, or mounted to the anesthesia workstation. Stimulator wires are connected to surface electrodes placed on the skin along the course of a peripheral nerve, optimally positioned to avoid direct stimulation of the muscle being monitored. The negative electrode is placed distally and the positive electrode proximally to ensure most effective neurostimulation 13,14]. Nerves that may be monitored — Several sites are commonly used for neuromuscular monitoring during administration of neuromuscular blocking agents (NMBAs). Response to stimulation varies among different muscles at the same level of neuromuscular block. (See ‘Differential muscle sensitivity’ below.)Ulnar nerve — The ulnar nerve is the preferred site for peripheral nerve stimulation, since it is generally readily accessible and the results are not confounded by direct muscle stimulation: a single ulnar nerve branch crosses over to the radial side of the hand and innervates the adductor pollicis (AP) muscle. The response is assessed at the AP muscle by monitoring adduction of the thumb. Maximal neuronal stimulation and muscular response are achieved by placing the negative electrode one centimeter proximal to the wrist crease, with the positive electrode four to five centimeters proximally along the ulnar surface of the volar forearm ( figure 1) [13]. The abductor digiti minimi (ADM) can also be monitored when stimulating the ulnar nerve, but such monitoring is generally reserved for electromyographic (EMG) monitoring. (See ‘Electromyography (EMG) below.) Facial nerve — Facial nerve stimulation is less accurate than ulnar nerve stimulation, but may be necessary if surgical positioning limits access to the hands or feet (eg, with the patient's arms tucked at the sides under surgical drapes during laparoscopic pelvic surgery). In one prospective cohort study, 150 patients who received NMBAs during anesthesia were assessed for residual paralysis using acceleromyography in the post anesthesia care unit [15]. Fifty-two percent of patients who were subjectively monitored with facial nerve stimulation had residual paralysis (ie, train-of-four [TOF] ratio <90 percent), compared with 22 percent of patients who had subjective ulnar nerve monitoring. If facial nerve monitoring is used during surgery, ulnar nerve stimulation should be used to confirm adequate reversal of neuromuscular block before extubation, preferably by objective means. (See ‘Differential muscle sensitivity’ below.) Facial nerve electrodes are placed on the mastoid process and just anterior to the tragus of the ear, to minimize the risk of direct muscle stimulation ( figure 2) [16]. Both electrodes can also be placed anterior to the ear, along the course of the facial nerve. Contraction of the orbicularis oculi (at the eyelid) or the corrugator supercilii muscle (at the eyebrow) is subjectively assessed by palpation (or visually) in response to stimulation. Acceleromyographic (quantitative) monitoring is possible (and recommended) at both corrugator supercilii and orbicularis oculi muscles (__ figure 3) [17]. (See 'Acceleromyography (AMG) below.) Importantly, during recovery from neuromuscular block, recovery of the stimulation response at the muscles around the eye may not reflect a degree of recovery in other muscles that would allow safe extubation. (See ‘Differential muscle sensitivity’ below.) Posterior tibial nerve — The posterior tibial nerve can be stimulated by placing electrodes superior to the medial malleolus and monitoring the response (flexion) of the great toe (figure 4), Paralyzed limb — Neuromuscular monitoring should not be performed on a paralyzed limb. Upregulation of acetylcholine receptors after denervation results in resistance tonondepolarizing NMBAs, and variable exaggeration of the TOF ratio(TOFR) in paretic limbs [18,19]. Thus, the degree of systemic neuromuscular block may be underestimated if a paretic limb is monitored. Patterns of stimulation — A variety of patterns of neurostimulation may be used to monitor the degree of neuromuscular blockade. The most commonly used stimulation patterns are the TOF, tetanus, and post-tetanic count. Responses to patterns of stimulation differ between depolarizing and nondepolarizing block Single twitch — Single-twitch (ST) stimulation involves one supramaximal neurostimulation every 10 seconds (__ figure 5), ST stimulation is used to determine the potency of NMBAs and is not used clinically. Train-of-four — TOF stimulation consists of four successive supramaximal stimuli delivered at 2 Hz, no less than 10 seconds apart (__ figure 6). After administration of a nondepolarizing NMBA, responses at this frequency show fade, or progressively decreasing amplitude of the responses (figure 6). A TOFR is calculated by dividing the amplitude of the fourth response by the amplitude of the first response, and requires an objective measure of the response to stimulation. With progressive nondepolarizing block, the fourth twitch disappears, followed by the third, then the second, and finally the first (figure 6). As neuromuscular block dissipates, the TOF twitches reappear one by one, with the degree of fade decreasing as full neuromuscular function returns. The TOF count (TOFC) is defined as the number of detectable evoked responses, and it correlates with the degree of neuromuscular block, as follows [20]: * TOFC = 1 : >95 percent of nicotinic acetylcholine receptors (nAChRs) blocked * TOFC = 2: 85 to 90 percent of nAChRs blocked * TOFC = 3: 80 to 85 percent of nAChRs blocked * TOFC = 4: 70 to 75 percent of nAChRs blocked With depolarizing block, fade does not occur, and all four twitches decline in amplitude to a similar extent( figure 6), unless phase II block occurs. Fade in response to TOF stimulation or tetanus, and post-tetanic potentiation, are signs of development of depolarizing phase II block. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on ‘Phase I block',) Depth of block and the use of TOF stimulation during endotracheal intubation, maintenance of anesthesia, and reversal of NMBAs is discussed below and in a separate topic. (See "Clinical use of neuromuscular blocking agents in anesthesia" and ‘Differential muscle sensitivity’ below.)Tetanus — Tetanic stimulation, also called tetanus, involves repetitive stimulation at a frequency of >30 Hz for 5 seconds, which causes sustained muscle contraction (figure 7). Tetanic contraction fades as the level of nondepolarizing NMBA-induced blockade increases (figure 8 and figure 9), and the degree of fade is equivalent to the fade with TOF stimulation. Tetanus should be performed at a frequency below approximately 60 Hz, which is the frequency at which voluntary muscle contraction occurs. At a supraphysiologic frequency, tetanic fade may occur even in the absence of NMBA [21]. Post-tetanic potentiation — Post-tetanic count (PTC) consists of a five-second tetanic (50 Hz) stimulus, followed by a series of ST stimuli delivered at 1 Hz for 20 seconds. Tetanus transiently mobilizes presynaptic acetylcholine (Ach) release into the neuromuscular junction, and therefore the response to subsequent stimulation is potentiated ( figure 8). This pattern is useful during deep levels of nondepolarizing neuromuscular block with a TOFC of zero. If PTC is 1, spontaneous recovery from intermediate-acting NMBAs to a TOFC of 1 can take up to 30 minutes [22]. The TOF count and ratio, and apparent recovery from neuromuscular block, are increased for a variable period of time after tetanus [23,24]. Thus, TOF monitoring at the same site after tetanic stimulation may lead to either unnecessary intraoperative administration of additional NMBA, or overestimation of the degree of recovery at the end of surgery. As such, we suggest waiting two to three minutes after tetanic stimulation before resuming TOF monitoring. Assessing the response to tetanic stimulation during moderate levels of block (when TOFC is 1 to 3) yields no useful information and should not be used. Double burst stimulation — Double-burst stimulation was developed because the assessment of two, instead of four, stimuli might allow more accurate subjective assessment of fade. The two mini-tetanic bursts are delivered 0.75 seconds apart. As in TOFR, the ratio is determined by comparing the second muscle response to the first (__ figure 9). In awake patients, it is less painful than tetanic stimulation [25] but it is more painful than TOF. When objective monitoring is used, it offers no advantage over the more widely used TOF pattern. QUALITATIVE VERSUS QUANTITATIVE MONITORING * Qualitative monitoring refers to visual or tactile (ie, holding the patient's thumb and feeling movement) evaluation of the train-of-four count (TOFC) or degree of train-of- four (TOF) fade in response to neurostimulation provided by a peripheral nerve stimulator (figure 1). Qualitative monitoring is sometimes referred to as subjective monitoring.* Quantitative, or objective, monitors actually measure the response of the muscle to the neurostimulation, and should be used whenever they are available. (See ‘Quantitative monitoring’ below.) Assessment of the degree of neuromuscular block using qualitative evaluation is less accurate than quantitative evaluation, both when assessing the TOFC and TOF ratio (TOFR). Thus, qualitative evaluation with a peripheral nerve stimulator may provide inaccurate information regarding the level of blockade, which may have implications for the dose and type or reversal agent used, as well as the timing of tracheal extubation, If a quantitative monitor is not available, qualitative monitoring with a peripheral nerve stimulator should be used, recognizing the limitations of subjective assessment. Suggested management according to monitoring and a comparison of the depth of block based on quantitative and qualitative monitoring are included in tables( table 1and table 2). * Assessing TOFC - Clinicians tend to overestimate the TOFC when using subjective evaluation, especially at moderate levels of block. In one study including 90 patients who were recovering from an intubating dose of rocuronium or vecuronium, the TOFC was assessed subjectively by clinicians and simultaneously with acceleromyography (AMG) [26]. The TOFC was the same in 36 percent of measurements at a TOFC of 1 to 3, and 87 percent at TOFC of 0 or 4; 96 percent of disagreements were overestimates using subjective assessment. * Assessing fade - Similarly, the level of fade is difficult to detect subjectively, with most clinicians unable to detect fade when TOFR >0.4 [27-30]. Multiple studies have reported residual neuromuscular block (ie, TOFR <0.9 measured by quantitative monitors) despite the use of subjective monitoring with a peripheral nerve stimulator [31]. (See "Clinical use of neuromuscular blocking agents in anesthesia’, section on ‘Avoidance of residual neuromuscular blockade.) ‘A 2020 meta-analysis of 53 observational and randomized trials found that for patients who received intermediate-acting NMBAS (ie, atracurium, cisatracurium, mivacurium, vecuronium, or rocuronium), the use of quantitative neuromuscular monitoring was associated with a reduced incidence of postoperative residual neuromuscular block, compared with qualitative (subjective) monitoring, or no monitoring at all (11.5 versus 30.6 versus 33.1 percent, respectively) [32]. However, the quality of the data was judged to be very low. QUANTITATIVE MONITORING Types of quantitative monitors — Several types of quantitative neuromuscular monitors are available, and they are categorized by the method they use to obtain quantitativemeasurements (ie, the monitoring modality). Some monitors are hand held, portable devices, whereas others are fixed devices integrated into the anesthesia work station, Available monitors use electromyography (EMG), acceleromyography (AMG), or less commonly, kinemyography (KMG). In research settings, mechanomyography has been used in the past and was the standard for comparison of new devices, but it cannot be used clinically and the devices are no longer manufactured. Choice of quantitative monitor — When an EMG monitor is available, we suggest using EMG rather than AMG or KMG. Relative advantages of EMG include the following: EMG monitors do not require unrestricted movement of the stimulated muscle. This is important because increasingly the arms are tucked at the patient's side during surgery, such that AMG or KMG cannot be used without a special device protecting the hand * Unlike AMG, EMG is not subject to reverse fade, so that baseline TOFR is typically approximately 1.0 with EMG monitoring. Thus, normalization of the TOFR is not required when assessing block reversal with EMG. Reverse fade and normalization are described below. (See ‘Acceleromyography (AMG)' below.) + EMG monitors have a high level of agreement with mechanomyography [33], and better agreement than AMG [34]. * EMG monitors are better indicators of adequate recovery than AMG, as a result of greater precision and repeatability [35]. Relative disadvantages of EMG monitors are that they may be affected by electrical interference in the operating room (eg, electrocautery), which is not a problem with AMG or KMG, and they require manufacturer-specific electrode strips, which are significantly more expensive than the standard ECG electrodes used for AMG and KMG. Electromyography (EMG) — EMG monitors use stimulating skin surface electrodes to generate an action potential of the target peripheral nerve, and then measure the evoked muscle response (action potential). These monitors do not require the needle electrodes that are usually used for EMG performed for diagnosis of neurologic disease or intraoperative neuromonitoring. (See "Neuromonitoring in surgery and anesthesia’, section on ‘Electromyography'.) For monitoring neuromuscular blockade, EMG electrodes are typically placed over the ulnar nerve, after which the muscle response is measured at the adductor pollicis, abductor digiti minimi, or first dorsal interosseus muscle (picture 1). EMG monitors can use the same patterns of stimulation described above, and report a train-of-four (TOF) count and ratio. One benefit of EMG monitors is that they do not require unrestricted motion of the hand and therefore can be used when the arms are tucked at the patient's side. When recordedsimultaneously, TOF ratios (TOFR) are higher with AMG monitoring than with EMG monitoring; however, recovery is still defined by a TOFR >0.9 as measured at the adductor pollicis with either modality [36]. Unlike AMG, EMG monitoring is not associated with the “reverse fade," phenomenon. and there is a high level of agreement between newer EMG devices and newer AMG devices [37]. Given its high level of agreement with mechanomyography (the traditional gold standard for objective monitoring) and utility when the limbs are restricted, many experts feel EMG has become the new gold standard for objective monitoring [38,39]. There are several standalone handheld EMG monitors available (eg, TetraGraph, Twitchview) as well as a monitor that is incorporated into the anesthesia workstation. The E-NMI device is a component of the General Electric Datex-Ohmeda workstation. Acceleromyography (AMG) — For AMG using the adductor pollicis muscle (APM), skin surface electrodes are placed over the ulnar nerve, and an accelerometer mounted to the thumb measures acceleration in response to ulnar nerve stimulation, This technique is based on the Newton's Second Law of Motion (ie, force = mass x acceleration), such that the force exerted by the thumb is proportional to measured acceleration, since mass doesn’t change. The monitor displays a TOF count (TOFC), and when there are four twitches, a TOFR. For AMG the arm position must stay the same throughout the monitoring period, and the thumb must be free to move, unimpeded by surgical drapes or positioning. Therefore, AMG cannot be applied to an arm that is tucked at the patient's side, unless the arm is placed in a special protective device (__ picture 2). Following induction of general anesthesia, the AMG device should optimally be calibrated and a baseline TOFR established prior to administration of NMBA. * Calibration refers to a process the device performs to determine the optimal current that will achieve supramaximal stimulation, independent of the monitoring modality. During calibration, the device delivers increasing current in 10 mA increments and sets the stimulation at 10 mA above that which achieves maximal stimulation. If calibration is not performed, most monitors default to a current of 50 to 60 mA. * Establishing a baseline TOFR is necessary for accurately interpreting data from AMG monitors, particularly when assessing recovery from neuromuscular block. The baseline TOFR in the absence of neuromuscular blockade measured by AMG at the adductor pollicis muscle is often >1.0 (>100 percent), and may be as high as approximately 1.5 [40]. Thus, when assessing the degree of reversal, the goal should be achieving a TOFR 20.9 times baseline rather than an absolute value of 0.9. Correction for the baseline TOFR is called normalization. For example, if the baseline TOFR before administration of NMBA is 1.2, the normalized value when assessing for safe recovery would be 0.9 x 1,2 = 1,08. If the TOFR of 0.9 is used in this circumstance, the patient'snormalized recovery value would be 0.9 / 1.2 = 0.75, which would not indicate adequate recovery for extubation. The effect by which the TOFR exceeds 1.0 by accelerometry is called the reverse fade phenomenon; its mechanism has not been elucidated. To address this phenomenon, some monitors default to displaying the ratio of the fourth twitch to the second (T4/T2), and others report a baseline numerical value of 100 percent for any value 2100 (though the raw data is displayed on a bar graph) [41]. Whereas the monitor using T4/T2 rather than T4/T1 may affect the conduct of research involving neuromuscular blockade, this is unlikely to be a relevant issue when these devices are used clinically. The early versions of AMG transducers measured acceleration in one plane of motion (TOF- Watch, TOF-Watchs S, TOF-Watch SX), and are no longer commercially available. Newer AMG monitors (eg, TOFScan, StimPOD) use three dimensional transducers that were developed to account for the complex motion of muscles in response to neurostimulation and have demonstrated good agreement with mechanomyography and normalized single plane accelerometers [42]. Per the manufacturer's directions, calibration is unnecessary for the TOFScan as the device defaults to 50 mA output. Normalization is not performed since the device limits the numerical display of the TOFR to <1.0. The TOFScan device includes a hand adapter that stabilizes the position of the thumb and is embedded with the accelerometry sensor. In addition to its 3D transducer, the StimPOD device has both AMG and EMG capabilities. Kinemyography (KMG) — KMG measures the electrical signal generated from the distortion (bending) of a mechanosensor that is placed at the base of the thumb and index finger. KMG results are not interchangeable with other quantitative modalities, and the technology has similar limitations as AMG, being dependent on freely moving muscles [43]. However, KMG is an easy to use modality and is a much more reliable monitor than subjective assessment with a peripheral nerve stimulator. A KMG device is available on General Electric anesthesia machines. DIFFERENTIAL MUSCLE SENSITIVITY Muscle groups respond differently to neuromuscular blocking agents (NMBAs), such that the monitored twitch response may not accurately reflect neuromuscular transmission in clinically important muscles (eg, airway muscles and diaphragm) ( table 2 and figure 10). After NMBA administration, neuromuscular block occurs faster in central muscles (eg, larynx and diaphragm) than peripheral muscles (adductor pollicis, flexor hallucis) [44-48], because of greater blood flow and drug delivery to the central muscles. However, the diaphragm is also more resistant to the effects of nondepolarizing NMBAs, and recovers faster, because it has a higher density of nAChRs [49]The response to stimulation at the corrugator supercilii muscle (at the eyebrow) correlates closely with neuromuscular block at the diaphragm and larynx [17,46], whereas stimulation at the orbicularis oculi correlates closely with the adductor pollicis muscle [17]. However, in practice it is difficult to separate the responses of these two muscles, and therefore facial nerve stimulation may overestimate the degree of recovery from neuromuscular block [15]. The sequence of recovery of various muscles after nondepolarizing neuromuscular blockade is as follows (fastest to slowest): diaphragm > laryngeal muscles > corrugator supercilii > abdominal muscles > orbicularis oculi > geniohyoid muscle (upper airway) > adductor pollicis muscle( figure 10) [17,44-47,49]. The clinical implications of the difference in sensitivity of various muscles include the following: * During intubation if deep neuromuscular blockade is confirmed by monitoring adductor pollicis or flexor hallucis stimulation, pharyngeal muscles are usually blocked as well, and optimal intubating conditions are achieved. * During surgery, the absence of a twitch at the adductor pollicis muscle (APM) does not guarantee that the diaphragm will be paralyzed. A post-tetanic count of 1 or 2 at the APM indicates deep block, but diaphragm movement is still possible. * During recovery from neuromuscular block, a train-of-four ratio (TOFR) >0.9 at the APM. represents full recovery; the airway muscles and diaphragm have recovered fully. * Monitoring facial muscles will overestimate the degree of recovery. If the arms are not accessible due to surgical positioning, monitor the facial muscles but transition to the arms once they become available. SUMMARY AND RECOMMENDATIONS * Quantitative monitoring preferred - We suggest the use of quantitative, objective measurement of neuromuscular function to monitor administration of and recovery from neuromuscular blocking agents (NMBAs) whenever possible. If a quantitative monitor is not available, a peripheral nerve stimulator may be used with subjective evaluation, recognizing the limitations of the technology ( _ figure 1). Clinical tests (ie, grip strength, vital capacity, head lift) are not sensitive or specific for detection of residual weakness. (See 'When and how to monitor neuromuscular blockade’ above.) * Peripheral nerve stimulation - Neuromuscular monitoring for NMBAs most commonly involves the use of a peripheral nerve stimulator, with stimulation of a nerve and assessment of the muscle response.+ Monitoring site - The ulnar nerve is the preferred monitoring site, with response assessed in the adductor pollicis muscle(__ figure 1). (See ‘Peripheral nerve stimulation’ above.) + Stimulation patterns - The most commonly used patterns of stimulation include a train-of-four (TOF) stimuli, tetanus, and post-tetanic potentiation. Double burst stimulation may be used as well( table 1), (See ‘Patterns of stimulation’ above.) - TOF stimulation consists of four successive supramaximal stimuli delivered at 2 Hz, no less than 10 seconds apart(__ figure 6). With progressive nondepolarizing block, the amplitude of successive twitches in the TOF decrease, or fade, and ultimately the twitches disappear one by one. The TOF ratio (TOFR) (ie, ratio of the amplitude of the fourth to the first twitch) and the TOF count (TOFG; ie, the number of twitches that occur after TOF stimulation) are used as measures of the degree of nondepolarizing neuromuscular block. With depolarizing block, fade does not occur during TOF stimulation, unless phase II block develops. (See 'Train-of-four' above.) - Tetanic stimulation, also called tetanus, involves repetitive stimulation at a frequency of >30 Hz for 5 seconds, which causes sustained muscle contraction. With increasing nondepolarizing block, tetanic contraction fades (figure 7). (See ‘Tetanus above.) ~ Post-tetanic count (PTC) consists of a five-second tetanic (50 Hz) stimulus, followed by a series of single stimuli delivered at 1 Hz for 20 seconds (figure 7). Post-tetanic potentiation, or increase in PTC, is a characteristic of nondepolarizing neuromuscular block, and is useful during deep levels of block with a TOFC of zero(_ figure 8). The TOFC and TOFR are increased, or potentiated, for a variable period of time after tetanus. Therefore, tetanus should not be used during moderate levels of neuromuscular block (ie, TOFC 1 to 3), and TOF stimulation should not be used for two to three minutes after tetanus, to avoid underestimating the degree of neuromuscular block. (See 'Post-tetanic potentiation’ above.) * Quantitative monitors - Options for quantitative, objective monitoring include electromyography (EMG), acceleromyography (AMG), and less commonly, kinemyography (KMG). Some experts believe that EMG should be the gold standard for objective intraoperative neuromuscular blockade monitoring, since EMG does not require unrestricted movement of the stimulated muscle, and does not require normalization of the TOFR. (See ‘Choice of quantitative monitor’ above.)ACI + EMG monitors use stimulating skin surface electrodes to generate an action potential of the target nerve, and then measure the evoked muscle response (action potential) ( picture 1). (See ‘Electromyography (EMG)' above.) + For AMG using the adductor pollicis muscle (APM), skin surface electrodes are placed over the ulnar nerve, and an accelerometer mounted to the thumb measures acceleration in response to ulnar nerve stimulation. The baseline TOFR with an AMG. monitor is often >1.0. If so, safe reversal of neuromuscular blockade is ensured by aiming for a normalized TOFR, calculated as >90 percent of the baseline TOFR (picture 2), (See ‘Acceleromyography (AMG)' above.) * Differential muscle sensitivity - Differential muscle sensitivity must be recognized when interpreting the results of neuromuscular monitoring ( figure 10 and table 2). (See ‘Differential muscle sensitivity’ above.) 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Forty years of neuromuscular monitoring and postoperative residual curarisation: a meta-analysis and evaluation of confidence in network meta-analysis. Br J Anaesth 2020; 125:466. Engbaek J, Roed J, Hangaard N, Viby-Mogensen J. The agreement between adductor pollicis mechanomyogram and first dorsal interosseous electromyogram. A pharmacodynamic study of rocuronium and vecuronium, Acta Anaesthesiol Scand 1994; 38:869.34, Bowdle A, Bussey L, Michaelsen K, et al. A comparison of a prototype electromyograph vs. a mechanomyograph and an acceleromyograph for assessment of neuromuscular blockade. Anaesthesia 2020; 75:187. 35. Nemes R, Lengyel S, Nagy G, et al. Ipsilateral and Simultaneous Comparison of Responses from Acceleromyography- and Electromyography-based Neuromuscular Monitors. Anesthesiology 2021; 135:597. 36. Kopman AF, Chin W, CyriacJ. Acceleromyography vs. electromyography: an ipsilateral comparison of the indirectly evoked neuromuscular response to train-of-four stimulation, Acta Anaesthesiol Scand 2005; 49:316. 37. Renew JR, Hernandez-Torres V, Logvinov I, et al. Comparison of the TetraGraph and TOFscan for monitoring recovery from neuromuscular blockade in the Post Anesthesia Care Unit. J Clin Anesth 2021; 71:110234. 38. Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned, Part I: methods to reduce the risk of residual weakness. Anesth Analg 2010; 111:129. 39, Fuchs-Buder T, Claudius C, Skovgaard LT, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007; 51:789. 40. Suzuki T, Fukano N, Kitajima O, et al. Normalization of acceleromyographic train-of-four ratio by baseline value for detecting residual neuromuscular block. Br J Anaesth 2006; 96:44, 41. Kopman AF, Kopman DJ. An analysis of the TOF-watch algorithm for modifying the displayed train-of-four ratio, Acta Anaesthesiol Scand 2006; 50:1313 42. Murphy GS, Szokol JW, Avram MJ, et al. Comparison of the TOFscan and the TOF-Watch SX during Recovery of Neuromuscular Function. Anesthesiology 2018; 129:880. 43. Stewart PA, Freelander N, Liang 5, et al. Comparison of electromyography and kinemyography during recovery from non-depolarising neuromuscular blockade. Anaesth Intensive Care 2014; 42:378, 44, Wright PM, Caldwell JE, Miller RD. Onset and duration of rocuronium and succinylcholine at the adductor pollicis and laryngeal adductor muscles in anesthetized humans Anesthesiology 1994; 81:1110. 45. Meistelman C, Plaud B, Donati F. Neuromuscular effects of succinylcholine on the vocal cords and adductor pollicis muscles. Anesth Analg 1991; 73:278. 46. Donati F, Meistelman C, Plaud B. Vecuronium neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis. Anesthesiology 1991; 74:83. 47. Hemmerling TM, Schmidt J, Hanusa C, et al, Simultaneous determination of neuromuscular block at the larynx, diaphragm, adductor pollicis, orbicularis oculi and corrugator supercilii muscles. Br J Anaesth 2000; 85:856.48. Sopher MJ, Sears DH, Walts LF. Neuromuscular function monitoring comparing the flexor hallucis brevis and adductor pollicis muscles. Anesthesiology 1988; 69:129. 49. Donati F, Meistelman C, Plaud B. Vecuronium neuromuscular blockade at the diaphragm, the orbicularis oculi, and adductor pollicis muscles. Anesthesiology 1990; 73:870. Topic 114324 Version 22.0GRAPHICS Subjective evaluation of neuromuscular responses at the adductor pollicis!) = = ee coroz0i6 Subjective (tactile) evaluation of neuromuscular responses at the adductor pollicis (thumb) muscle in response to ulnar nerve stimulation. Note the negative (black) electrode is placed distally. Reference: 1. Naguib M, Bull Johnson KB. Conceptual and technical insights into the basis of neuromuscular monitoring. Angesthesia 2017; 72 Suppl 1:16. Reprinted with permission, Cleveland Clinc Center for Medical Art & Photography ©2016-2017. All Rights Reserved. Graphic 114145 Version 1.0,Placement of stimulating electrodes for monitoring of eye!"! P CCF ©2016 Suggested placement of stimulating electrodes for monitoring of the eye (orbicularis oculi, corrugator supercilil) muscles. Given the course of the facial nerve, note that the positive (red) electrode is always proximal and the negative (black) electrode always distal. Reference: 1. Naguib M, Brull 5}, Johnson KB. Conceptual and technical insights into the basis of neuromuscular monitoring. Anaesthesia 2017; 72 Suppl 1:16. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2016-2017. All Rights Reserved, Graphic 114147 Version 1.0Placement of electrodes for facial nerve monitoring using acceleromyograp| Apparatus for objective monitoring of the orbicularis oculi (A) and the corrugator supercilii (B) muscle cc using acceleromyography. An accelerometer is attached to the eyelid (A) or the eyebrow (B). Facial nerve (note that the negative electrode is distal to the positive electrode) will result in contraction of the eye m which is measured by the accelerometer. The results are displayed on the monitor's screen. Reprinted with permission. Copyright © 2020 Cleveland Clinic Center for Medical Art & Photography. ll Rights Reserved. Graphic 128514 Version 1.0Lower extremity mor coring!) CCF ©2016 An accelerometer is attached to the plantar surface of the large toe. The stimulating electrodes are placed along the posterior tibial nerve (posterior to the medial malleolus). Stimulation causes plantar flexion of the toes. Note the negative (black) electrode is placed distally. Reference: 1. Naguib M, Brull 5} Johnson KB. Conceptual and technical insights into the basis of neuromuscular monitoring. Anaesthesia 2017; 72 Suppl 1:16. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2016-2017. All Rights Reserved. Graphic 114146 Version 1.0Single twitch stimulation Bl comet pana Bock odessa halo, eres — stn same 7 Sra eae i 3 | 5 | & $ | $8 | g 2 i z +: g 3 ae 3 it ae Depiction of muscle contractions in response to single twitch (ST) stimuli delivered at a frequency of 0.1 Hz during normal conduction (control, A); partial depolarizing block (B); and moderate, shallow or minimal non-depolarizing block (C). Note the lack of fade between the first ST and subsequent ST evoked responses during both depolarizing and non-depolarizing block when stimuli are delivered at this slow, 0.1 Hz frequency. For this and other figures, the control value is that of the evoked mechanical response of the adductor pollicis muscle (in N) to a supramaximal stimulation of the ulnar nerve. From: Naguib M, Brull 5 Johnson KB. Conceptual and technical insights into the basis of neuromuscular monitoring. ‘Anaesthesia 2017; 72 Suppl 1:16. https//onlinelibrary.wiley.com/journal/13652044. Copyright © 2017 Association of ‘Anaesthetists. Reproduced with permission of john Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley’s permissions department either via email: [email protected] or use the RightsLink service by licking con the ‘Request Permission’ link accompanying this article on Wiley Online Library (ttps:/onlinelibrary.wile.com). Graphic 120555 Version 1.0,Train-of-four stimulation A El el oe eee eee 5 i 5 g 2 é i i i o eee ceeceos 3[ FTOFR = 01 : hove z i EE if fea "meme - | & == rasa z i The train-of-four ratio (TOFR) is calculated as the ratio between the fourth twitch (74) of the train-of four (TOF) sequence and the first (T1) (A) In the unblocked muscle the TOFR is 1. (B) During a partial depolarizing block there is minimal, if any, fade such that the TOFR remains close to 1. (©) During a partial non-depolarizing block, T4 decreases preferentially, followed by 73, then 2, and lastly, T1. The decrease in TOFR from the normal ratio of 1 is called "fade". (D)A set of two TOF stimuli are recorded, followed by administration of rocuronium. Over the ensuing three sets of TOF stimuli, the TOFR remains atbaseline (ie, TOFR 1), followed by progressive increase in fade (decrease in TOFR) from 0.81 to 0 during neuromuscular block onset. (E) During recovery of block the TOFR increases progressively towards 1 (F) During recovery from 1 mg/kg succinylcholine there is no significant fad the train-of four (TOF) response. At 8% recovery of T1 (the first twitch in the train- of-four), the TOFR was 0.89 and at 96% recovery of T1, the TOFR was 1.04. From: Naguib M, Brull Sj Johnson KB, Conceptual and technical insights into the basis of neuromuscular monitoring. Anaesthesla 2017; 72 Suppl 1:16. https/ontinelibrary.wiley.com/journal/13652044, Copyright © 2017 Association of Anaesthetists. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: [email protected] or use the RightsLink service by clicking on the ‘Request Permission’ link accompanying this article on Wiley Online Library (https:/ontinelibrary.wiley.com). Graphic 120570 Version 1.0,Tetanic stimula in and post-tetanic count (PTC) al B 10 seconds 100% control 100% control 10 second= 10 seconds. 100% control 100% control (A) In the unblocked muscle, the mechanical response to a 50 Hz tetanic stimulation is characterized by « sustained contraction with no fade or post-tetanic potentiation. (8) Application of tetanus during deep block resulted in a faint contraction for 5 seconds, and post-tetan potentiation that results in eight progressively weaker contractions (PTC = 8). Note that when measuring the PTC one always uses 1 Hz stimulation. (©) Single twitch is repeated every 12 seconds, followed by a 5 second tetanus, then decay to an amplitu: lower than the pre-tetanic single twitch amplitude. The pre-tetanic stimulus twitch amplitude is 16% of t control value and the first post-tetanic twitch amplitude increased to 76% of the control value. (0) With further spontaneous recovery of neuromuscular blockade, the tetanic and post-tetanic twitch ides increase. From: Naguib M, Brull S|, Johnson KB. Conceptual and technical insights into the basis of neuromuscular monitoring. Anaesthesit 2017; 72 Suppl 1:16. https:/onlinelibrary.wiley.com/journal/13652044. Copyright © 2017 Association of Anaesthetists. Reproduci‘with permission of john Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed, Please contact Willey's permissions department either vic email: [email protected] or use the RightsLink service by clicking on the ‘Request Permission’ link accompanying this article ‘on Wiley Online Library (https://onlinelibrary.wiley.com). Graphic 120571 Version 1.0Post-tetanic potentiation 10 seconds 4 100% contro! Tetanic stimulation results in apparent acceleration of recovery during the period of post-tetanic potentiation. TOFC is 3 before the tetanus and the recovery is falsely accelerated to a TOFR of 0.3 due to post-tetanic facilitation. ‘TOFR: train-of-four ratio; TOFC: train-of-four count. From: Naguib M, Brul SJ Johnson KB. Conceptual and technical insights into the basis of neuromuscular ‘monitoring. Anaesthesia 2017; 72 Suppl 1:16. https//onlinelibrary.wile.com/journal/13652044, Copyright © 2017 Association of Anaesthetists. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downfoaded to PowerPoint, printed, shared or emalied. Pease contact Wiley’s permissions department either via email [email protected] or use the RightsLink service by clicking an the ‘Request Permission’ link ‘accompanying ths article on Wiley Online Library (http://onlinelibrary.wiley.com). Graphic 120573 Version 1.0,Single twitch, double burst, and train-of-four stimula’ 10 seconds | 100% control Different patterns of stimulation (single twitch at 1 Hz, double burst stimulation [DBS3,2] and train- of four). DBS3,2 stimulation consists of a mini-tetanic sequence of three stimuli at 50 Hz, followed 750 ms later by two short simulit at 50 Hz. The pre-DBS twitch height was 14% of the control value. The amplitude of the first stimulus of DBS (D1) reaches 66% of Control amplitude. The train of four ratio is 0.18. 8S: double burst stimulation; TOF: train-of-four. From: Naguib M, Brull 5), Johnson KB. Conceptual and technical insights into the basis of neuromuscular monitoring. ‘Anaesthesia 2017; 72 Suppl 1:16, htps://onlinelibrary.wiley.conv/journal/13652044, Copyright © 2017 Association of ‘Anasesthetists. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: [email protected] or use the RightsLink servic by clicking on the ‘Request Permission’ link accompanying this article on Wiley Online Library (https//onlinelibrary.wile.conn/ Graphic 120574 Version 1.0Classification of depth of nondepolarizing neuromuscular blockade based on subjective and objective criteria secti Measured , , Subjective Depth of Posttetanic Train-of-four train-of-four (actual) train- block count (PTC) count (TOFC) * of-four (TOF) (TOF) ratio i ratio Intense 0 0 0 0 (profound) block Deep block 21 o 0 0 Moderate block NA 1t03 0 0 Light (shallow) NA 4 Fade present 0.1 to 0.4 block Minimal block NA 4 No fade >0.4 but <0.9 Full recovery NA 4 No fade 20.910 1.0 NA: data not available. Reproduced with permission from: Brull SJ. Neuromuscular blocking agents. In: Clinical Anesthesia, 8th ed, Barash PG, Cullen BF, Stoetting RK, et al (Eds), Wolters Kiuwer, Philadelphia 2017. Copyright © 2017 Wolters Kluwer. Graphic 114083 Version 3.0Suggested management of neuromuscular blockade according to monitoring Site Prediction of tracheal intubating condi Modality Response ions Interpretation Comments Any site Single twitch, Present Adequate Deep blockade is TOF conditions not required for met intubation Corrugator Single twitch, Absent Adequate Corrugator supercili TOF conditions likely | supercili reflects vocal cords and diaphragm Adductor Single twitch, Absent Adequate Adductor pollicis pollicis TOF conditions likely is more sensitive only ifhigh dose | than vocal cords given and diaphragm Flexor hallucis Single twitch, Absent Adequate Foot muscles are (foot) TOF conditions likely sensitive and only ifhigh dose block late given Intraoperative conditions Adductor PTC 1102 Deep blockade —_—Return of pollicis diaphragm movements possible, no TOF response at adductor pollicis Corrugator TOF 1102 Deep blockade —_—Return of supercili abdominal tone possible, no TOF response at adductor polices Adductor TOF 1102 Moderate Usually sufficient pollicis, blockade for most procedures Corrugator TOF 4, with or Moderate to Difficult to supercili without fade shallow blockade interpret without adductor pollicis, data Adductor TOF 4, with or Shallow blockade Additional pollicis without fade relaxation might be neededManagement of recovery Adductor pollicis ‘Adductor pollicis Corrugator supercili ‘Adductor pollicis Corrugator supercli Hypothenar eminence (fifth finger) Adductor pollicis Adductor pollicis ‘Adductor pollicis ‘Adductor pollicis Adductor pollicis PTC prc TOF TOF TOF TOF TOF, visual or tactile TOF, visual or tactile DBS, visual or tactile DBS, visual or tactile TOF, quantitative 1t02 1t02 4, with or without fade 4, with or without fade 4, with fade 4, without fade Fade No fade TOF ratio <0.90 Wait or sugammadex* 16 malkg Wait or sugammadex* 4 mg/kg Wait or sugammadex* 4 mg/kg Wait or sugammadex* 2 mg/kg Wait or correlate Corrugator with adductor supercili pollicis or recovers early sugammadex* 4 ma/kg Correlation with adductor pollicis preferable Observe thumb Adductor pollicis motion recovers later Wait or neostigmine 0.04 to 0.05 mg/kg or sugammadex* 2 mg/kg Wait or neostigmine! 0.020 mg/kg Wait or Less neostigmine! neostigmine 0.02 to 0.05 needed if no TOF mg/kg fade Wait or DBS fade neostigmine" detected when 0.020 mg/kg TOF ratio = 0.6 Wait or Neostigmine neostigmine 0.04 to 0.05 mg/kg if TOF ratio <0.4; 0.02 mg/kg if TOF ratio >0.4Adductor 100 Hz TET No fade No reversal 100 Hz TET fade pollicis necessary detected when TOF ratio = 0.8 to 09 Adductor TOF, quantitative | TOF ratio 20.9 No reversal Full recovery pollicis necessary Actual management depends on patient, surgical procedure, and previous response to neuromuscular blocking agents ‘TOF: train of four; PTC: posttetanic count; DBS: double burst stimulation; TET: 5-sec tetanic stimulation. * Sugammadex can be used to reverse only rocuronium or vecuronium, ‘ Neostigmine can be used to reverse any nondepolarizing neuromuscular blocking agent. Reproduced with permission from: Brull J. Neuromuscular blocking agents. In: Clinical Anesthesia, 8th ed, Barash PG, Cullen BF, Stoelting RK, et al (Eds), Wolters Kluwer, Philadelphia 2017. Copyright © 2017 Wolters Kluwer. Graphic 114082 Version 4.0Setup for EMG monitor This photo shows the Tetragraph EMG monitor. Similar to other EMG monitors for neuromuscular block: one requires a proprietary electrode strip. For further information, refer to UpToDate content on monite neuromuscular blockade. EMG: electromyography; TOF: train-of-four. Graphic 131801 Version 1.0,Setup for AMG monitor This graphic shows the TOFScan AMG monitor in use. The accelerometer is embedded in the hand adap! stabilizes the thumb. For further information, refer to UpToDate content on monitoring neuromuscular | AMG: acceleromyography; TOF: train-of-four. Graphic 131800 Version 1.0Differential muscle sensitivity to rocuro! 4100. 80 80 70 60 50 40. Twitch height (%) Time (minutes) Approximate time course of twitch height reduction and recovery at different muscles after administrati rocuronium 0.6 mg/kg IV. Larynx: laryngeal adductors (vocal cords); CS: corrugator supercilii muscle (eyebrow); Abd: abdominal mi orbicularis oculi muscle (eyelid); GH: geniohyoid muscle (upper airway); AP: adductor pollicis muscle (the intravenous. Reproduced with permission from: Brull J. Neuromuscular blocking agents. In: Clinical Anesthesia, 8th ed, Barash PG, Cullen BF, (Eds), Wolters Kluwer, Philadelphia 2017. Copyright © 2017 Wolters Kluwer Health. Graphic 115809 Version 2.0Contributor Disclosures Johnathan Ross Renew, MD Grant/Research/Clinical Trial Support: Merck [Neuromuscular blockade]. Other Financial Interest: Senzime Inc [Quantitative neuromuscular monitor J. All of the relevant financial relationships listed have been mitigated. Girish P Joshi, MB, BS, MD, FFARCSI Consultant/Advisory Boards: Baxter [anesthesia]. All of the relevant financial relationships. listed have been mitigated. Marianna Crowley, MD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy >