PADMAJA, MANTHA : MONITORING OF NEUROMUSCULAR JUNCTION Indian J. Anaesth.

2002; 46 (4) : 279-288

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MONITORING OF NEUROMUSCULAR JUNCTION

Dr. D. Padmaja1 Dr. Srinivas Mantha2
Introduction Neuromuscular blockers (NMBs) are widely used in anaesthesia practice. Simple quantitative method to monitor their effects is desirable. Neuromuscular junction (NMJ) monitors have proven to be useful adjuncts in clinical anaesthesiology practice. Traditionally, anaesthesiologists evaluated the degree of neuromuscular block during and after anaesthesia using clinical criteria alone. But the recommendation for application of neuromuscular monitoring to patients receiving NMBs is based on two important issues: first, on the variable individual response to muscle relaxants1 and second, because of the narrow therapeutic window. There is no detectable block until 75 to 85% of receptors are occupied and paralysis is complete at 90 to 95% receptor occupancy.2 Therefore adequate muscle relaxation corresponds to a narrow range of 85 to 90% receptor occupancy. Neuromuscular monitoring permits administration of NMBs such that optimal surgical relaxation is achieved and yet the block reverses spontaneously or reversed reliably and quickly with antagonists. It has been shown that when monitoring of NMJ function is not performed and clinical criteria alone are used, upto 42% of the patients are inadequately reversed upon arrival to the recovery room.3 Residual neuromuscular block is a major risk factor for many critical events in the immediate postoperative period such as ventilatory insufficiency, hypoxemia and pulmonary infections.4 The use of short acting NMBs and wide spread use of perioperative NMJ monitoring was found to be helpful in reducing these complications.5 This review describes the principles and practice of NMJ monitoring in clinical settings. The most satisfactory method for reliably monitoring neuromuscular function is the stimulation of an appropriate nerve using a peripheral nerve stimulator and observation of evoked response in the muscle supplied.
1. Assistant Professor 2. Additional Professor Dept. of Anaesthesiology and Intensive Care, Nizams Institute of Medical Sciences, Punjagutta, Hyderabad - 500082

Principles of peripheral nerve stimulation Equipment A number of contemporary monitors are available commercially. The desirable features of a nerve stimulator are listed below: Essential features Square-wave impulse, < 0.5 msec,> 0.1 msec duration.

Constant current variable voltage. Battery powered. Multiple patterns of stimulation (single twitch, train-of-four, double-burst, post-tetanic count).

Optional Features Rheostat for adjustable current output.

Polarity output indicator. Ability to calculate and display fade ratio and percentage depression of single twitch. High output (80-100 mA) and low output (<5 mA) sockets. Audible signal with each stimulus. Alarm for excessive impedence, lead disconnect, low battery. Battery charge indicator.

Features of Neurostimulation The key features of exogenous nerve stimulation are: Nerve stimulator: A battery powered device that delivers depolarizing current via the electrodes. The neurostimulation is described according to intensity of each impulse and frequency and pattern of impulse repetition. Stimulus strength: It is the depolarizing intensity of stimulating current. It depends on duration (pulse width) of the stimulus and on the current intensity that reaches the current nerve fibers. Pulse width: It is the duration of the individual impulse delivered by the nerve stimulator. Each impulse

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should be <0.5 msec and 0.1 msec in duration to elicit nerve firing at a readily attainable current. Pulse width >0.5 msec extends beyond the refractory period of the nerve resulting in repetitive firing. In addition, the stimulus strength is excessive which stimulates the muscle directly. The stimulus should produce monophasic and rectangular waveform. Current intensity: It is the amperage (mA) of the current delivered by the nerve stimulator. The current output of most stimulators can range from 0-80 mA. The intensity reaching the nerve is determined by the voltage generated by the stimulator and resistance and impedance of the electrodes, skin and underlying tissues. The preset current is typically attained and maintained by internal voltage adjustments unless there is excessive impedance. In other words, nerve stimulators are constant current and variable voltage delivery devices. Reduction of temperature increases the tissue resistance (increased impedance) and may cause reduction in the current delivered to fall below the supramaximal level. Ideally, a nerve stimulator should have a built in warming system or a current level display alert. Threshold current : It is the lowest current required to depolarize the most sensitive fibres in a given nerve bundle to elicit a detectable muscle response (Figure 1).

Stimulus frequency : The rate (Hz) at which each impulse is repeated in cycles per second (Hz). Single twitch is commonly repeated at 10 second intervals i.e. 0.1 Hz and tetanic stimulation commonly consists of 50 impulsessec1 i.e. 50 Hz.

Electrodes : Surface electrodes : They contain gel covered conducting surfaces for transmission of impulses to the nerves through the skin. The transcutaneous impedance can be reduced by rubbing an electrolye solution or conducting gel, decornifying or degreasing the skin. With careful skin preparation the threshold for twitch response is generally <15 mA. It may be noted that the regular ECG electrodes i.e. silver-silver chloride electrodes offer greater impedance than those recommended for NMJ monitoring.
Needle electrodes : Subcutaneous needles deliver the impulse in the immediate vicinity of the nerve. These are highly effective because they bypass the tissue impedence so that the tissue impedance is typically < 2000 Ohms. Disadvantages include local irritation, infection, nerve damage especially if placed intraneurally, diathermy burns and delivery of excessive amounts that may induce repetative nerve firing or direct muscle stimulation. Patterns of stimulation There are five commonly used patterns of stimulation for monitoring neuromuscular blockade.

Figure 1: Evoked tension response curve

Supramaximal current : It is approximately 10-20% higher intensity than the current required to depolarize all fibres in a particular nerve bundle. This is generally attained at current intensity 2-3 times higher than threshold current. Supramaximal current should be delivered when monitoring absolute twitch height to ensure constant recruitment of all fibres (Figure 1). Submaximal current : A current intensity that induces firing of only a fraction fibres in a given nerve bundle. A potential advantage of submaximal current is that it is less painful than supramaximal current.

Single twitch This is the simplest form of neurostimulation entailing a single 0.1 to 0.2 msec impulse. Single twitch is delivered at a supramaximal current, it induces a single nerve action potential in each fiber of the nerve bundle. The height of the evoked muscle response depends on the number of unblocked junctions. There are several potential limitations with this form of neurostimulation. The magnitude of the response cannot be interpreted unless it is compared to a prerelaxant control value. Unless a recording device is employed it is difficult to monitor and compare individual twitch heights over time. During nondepolarizing block the response to single twitch stimulation is not reduced until at least 75% to 80% of receptors are occupied and therefore does not detect the receptor block of less than 70%. Although these features limit the clinical applicability of single twitch stimulation, this mode is frequently used as a yard stick to assess potency of drugs or other modes of stimulation. For example, ED95 of drug is defined as the dose producing

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a mean 95% single twitch depression. The disappearance of fourth response after TOF stimulation corresponds to 70% to 75% single twitch depression. One cycle per second (1Hz) stimulation is used in the operating room to detect onset of neuromuscular blockade. However, this rate of stimulation results in faster apparent onset of neuromuscular block when compared 0.1Hz single twitch. This phenomenon is known as stimulation dependent onset time. This is most likely a consequence of stimulation induced increase blood flow with greater relaxant delivery and also neuromuscular fatigue.6 Subtle degrees of neuromuscular block of <75% that cannot be detected by monitoring single twitch can be detected by stressing the neuromuscular junction using a stimulus of greater frequency.

Table 1: Relationship between receptor occupancy, T1, T4, T4/T1 ratio and tetanus during nondepolorising block.
Percentage Blocked 100 95 T1 (% normal) 0 90 10 20 80 25 T4 (% normal) 0 T4/T1 (% normal) T1 lost T2 lost T3 lost T4 lost Onset of fade at 30 Hz Onset of fade at 50 Hz Onset of fade at 100 Hz Onset of fade at 200 Hz Tetanus

75 -

80-90 95 100 100

55-65 70 75-100 -

0.60-0.70 0.70-0.75 0.75-1 0.90-1

Train of four (Figure 2) This is a popular mode of stimulation for clinical monitoring of neuromuscular junction first described by Ali et al.7 Four successive stimuli are delivered at 2Hz (every 0.5 sec). At this frequency, the immediately available store of acetylcholine is depleted and the amount released by the nerve decreases with each successive stimulus until the fifth or sixth when it levels off.8 Even this lesser amount of neurotransmitter is enough to elicit contraction of normal muscle because of the wide margin of safety of neuromuscular transmission. In the presence of non depolarizing relaxants, the margin of safety is decreased such that some end plates fail to develop propagated action potentials.7 With increasing degrees of block, the twitches in train of four progressively fade

50

30

First twitch will serve as a accurate control only if 10 sec have elapsed since any previous stimulation. Therefore TOF stimuli should be delivered no more frequently than 12sec.8 Train of less than four response or stimuli at slower frequency rates tend to sacrifice fade sensitivity. Higher frequency begins to result in tetanus and muscle inertia complicates interpretation.10 During depolarizing neuromuscular blockade the train of four does not fade significantly. The height of all the four twitches decreases simultaneously. However, the TOF ratio has proved useful in assessing neuromuscular block in patients who exhibit prolonged response to depolarizing relaxant to diagnose and follow a dual or phase II block.11

Figure 2 : Responses to train-of-four stimulation at different phases of neuromuscular block

starting with the fourth and one by one eventually disappear. The ratio of the height of the fourth response to the first has been defined as the train of four ratio. In the absence of nondepolarsing block, the T4/T1 ratio is approximately one. There is a fair relationship between single twitch depression and train of four response.9 Table 1 shows the relationship between receptor occupancy, twitch height, fade of TOF, and tetanic stimulation.

Advantages of TOF stimulation : This pattern of stimulation can be applied at anytime during the neuromuscular block and can provide quantification of depth of block without the need for control measurement before relaxant administration. Also correlation of the depth of block with number of response frees the clinician from recording devices necessary to calculate a ratio. Observation of evoked TOF responses after small dose of nondepolarizer allows accurate prediction of dose requirement in individual patients. It is more sensitive to lesser degree of receptor of occupancy than single twitch. The degree of fade is similar to that at 50Hz stimulation

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and therefore provide same sensitivity but is less painful. The relatively low frequency allows response to be evaluated manually or visibly. There is no post tetanic facilitation therefore can be repeated every 10 to 12sec. It does not affect the degree of neuromuscular blockade. It may be delivered at sub maximimal current which is less painful and is associated with same degree of fade.12

Tetanic stimulation High frequency stimulation (50Hz or more) results in sustained or tetanic contraction of the muscle during normal neuromuscular transmission despite decrement in acetylcholine release. During tetanus, progressive depletion of acetylcholine output is balanced by increased synthesis and transfer of transmitter from its mobilization stores. The presence of nondepolarizing muscle relaxants reduces the margin of safety by reducing the number of free cholinergic receptors and also by impairing the mobilization of acetylcholine within the nerve terminal there by contributing to the fade in the response to tetanic and TOF stimulation. This is perhaps the most stressful method of stimulating the neuromuscular junction.13 There is a controversy over the optimal rate of tetanic stimulation. A frequency of 50Hz is physiological as it is similar to that generated during maximal voluntary effort. Some workers suggested that 100Hz or 200Hz may be more stressful and thus more sensitive indicator of smaller degrees of neuromuscular blockade.14 How ever fade can occur at 100Hz in anaesthetized patients even in absence of neuromuscular blocking drugs.15 Fade is first noted at 70% receptor occupancy. The tetanic fade ratio at the end of 1 second is comparable to that of T4/T1. It has been shown that tetanic response to 50Hz for five sec is sustained when TOF ratio is greater than 0.7. Although gradual decrease in the ability of nerve terminal to release acetylcholine should be more marked at 50Hz than at 2Hz, both elicit similar degree of neuromuscular fade. This is because, more rapid depletion of acetylcholine is offset by stimulation induced acetylcholine reuptake and mobilization presynaptically.16 No prerelaxant response is required as degree of paralysis can be assessed by fade. The main disadvantage is post tetanic facilitation which depends on frequency and duration of block. For 50Hz 5sec stimulation the duration is 1 to 2min, tetanic stimulation has several other drawbacks. It is very painful and therefore not suitable for unanaesthetised patients. It facilitates the neuromuscular response during and after its application, artificially shifting all subsequent neuromuscular events towards normality. Since it provides only one point on the continuum of neuromuscular response, it is less useful than TOF. Tetanic stimulation has very little place in day-to-day clinical anaesthesia except in the context of post tetanic count.

Double burst stimulation (DBS) TOF ratio of less than 0.2 to 0.3 is difficult to detect even by trained observers.16 To improve the detection rate, a new mode of stimulation which consist of two short tetani separated by a interval long enough to allow relaxation, evaluating the ratio of second to first response has been proposed.17 Many patterns have been suggested but the most promising one consists of two train of three impulses at 50Hz separated by 750msec. The magnitude of fade is similar to TOF fade but human senses detect DBS fade better.18 At least 12 to 15sec must elapse between two consecutive double burst stimulations. Post- tetanic count (PTC) During profound neuromuscular blockade, when there is no response to single twitch, tetanic or train of four stimulation, quantification of such neuromuscular blockade can be done by using post tetanic count that is based on the principle of post tetanic facilitation.19 Mobilization and enhanced synthesis of acetylcholine continue during and after cessation of tetanic stimulation. Following the end of tetanus, there is an increase in the immediately available store of acetylcholine and the quantal content. Thus after tetanus, there is an increase in the amount of transmitter released in response to nerve stimulation and a single twitch evoked after cessation of tetanus may be stronger than the pretetanic control. Even though acetylcholine mobilization may not be adequate to sustain the response to tetanic stimulation without fade, the accumulation of acetylcholine is sufficient to elicit evoked response of increased magnitude. Tetanus at 50 Hz for five seconds is applied followed 3 sec later by single twitch stimulation at 1 Hz. The number of evoked post tetanic twitches detected is called the post tetanic count (PTC). Tetanic stimuli are not repeated more often than every six minutes. The number of post tetanic twitch correlates inversely with the time for spontaneous recovery.19
Post tetanic count is a prejunctional event, the response can vary with the nondepolarising muscle relaxant used. Following intense neuromuscular blockade by vecuronium, the first detectable response of TOF will appear and average 8.5 min (6 to15min) after appearance of post tetanic twitch. A PTC of 8 to 9 indicates imminent return of TOF.20 The recovery of atracurium is similar to that of vecuronium.21 The interval is larger for pancuronium. It takes approximately 38 min after the first post tetanic twitch to reappearance of first response to TOF stimulation. A PTC of 9 to 11 predicts imminent return of TOF response. Children have a shorter interval between PTC 1 and onset of T1. This interval for vecuronium, atracurium and pancuronium is 5.8min 7.8min and 19.8min in children and 8.5min 9.min and 37min in adults22 respectively.

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The main application of PTC is evaluating the degree of neuromuscular blockade when there is no reaction to single twitch or TOF as after administration of large dose of nondepolarizing muscle relaxant. PTC can also be used whenever sudden movement must be eliminated (ophthalmic surgery). Elimination of responses to tracheobronchial stimulation requires intense neuromuscular blockade of zero PTC.23 PTC can be used during continuous infusion of intermediate nondepolarizing muscle relaxant as a guidance to intensity of neuromuscular blockade. During atracurium infusion, all responses to TOF stimulation are obliterated at a PTC of less than 10. PTC predicts time to reappearance of first response to TOF stimulation. Thus PTC is useful in predicting an appropriate time to attempt to reversal of nondepolarising blockade.20,21 Table 2 and Figure 3 summarize the patterns of neuromuscular stimulation encountered in clinical NMJ monitoring.
Table 2: Summary of Patterns of Neuromuscular Stimulation
Feature Current strength Frequency / Description ST Supramaximal 0.1 to 1 Hz TOF Supra or submaximal 2 Hz four stimuli Tetanus DBS PTC

Figure 3: Pattern of neuromuscular stimulation

Supra or Supra or Supra or submaximal submaximal submaximal 30-50 Hz for 5 sec 3 impulses at 50 Hz repeated after 750 msec Not needed + Highly sensitive 30 Hz for 5 sec, 3 sec later ST at 1Hz Not needed + + Sensitive

Prerelaxant Control Pain on stimulation Sensitivity of manual detection (visual/tactile) Alteration of subsequent responses Interval between successive stimuli Receptor occupancy detection Sensitivity for detection of subtle block Monitoring of profound block

Needed Not sensitive Not altered 5 sec 75-90%

Not needed - / +

Not needed + +

Monitoring Sites The specific nerve-muscle site utilized for monitoring has drawn interest in the recent years because of the variability among muscle groups in sensitivity and onset time. The actual cause for these differences is not clear. The possible causes may be differences in the margin of safety of the neuromuscular junction of different muscle groups, fibre composition, innervation ratio (number of neuromuscular junctions), blood flow and muscular temperature.24 Response artifacts can occur if paretic limb is used as a site for monitoring. Spread of extrajunctional cholinoreceptors occurs in the paretic muscles. Such receptors are relatively resistant to nondepolarizing NMBs resulting in exaggerated evoked responses.25 As the muscles of interest (diaphragm, abdominal or laryngeal muscles) are clinically not accessible, it would be appropriate to choose a site that has similar response to muscle of interest (Table 3).
Table 3: Relative sensitivities of muscle groups to nondepolarizing muscle relaxants
Muscle Vocal cord Sensitivity Most resistant

Not sensitive Sensitive at TOF ratio of 0.4-0.7 Not altered 12 sec 70-90%

Altered Not (post-tetanic altered facilitation) 6 min 70-90% 12-15 sec 70-90%

Altered

6 min >90% also

Diaphragm Orbicularis oculi

Not sensitive Not useful

Sensitive

Sensitive

Sensitive

Not applicable Useful

Abdominal rectus Adductor pollicis Masseter Pharyngeal Extraocular Most sensitive

Not useful

Not useful

Not useful

ST=single twitch, TOF=train of four, PTC = post-tetanic count, DBS = double burst stimulation

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Ulnar nerve The nerve is most commonly used for neuromuscular monitoring in the perioperative period. The ulnar nerve innervates the adductor pollicis, abductor digiti quinite, abductor policies brevis and dorsal interosseous muscles. One stimulating electrode is typically placed proximal to the wrist on the radial side of flexor carpi ulnaris and the other may be placed more than 2cm proximally on the volar forearm or over the olecranon groove. The recording electrodes are placed over the appropriate muscle.
Adductor pollicis muscle : This muscle has been promoted as the most useful clinical tool and is the gold standard because of its accessibility for visual, tactile and mechanographic assessment. There is less likelihood of direct muscle stimulation. The adductor pollicis muscle however exhibits different sensitivity and time course from the laryngeal muscles. Both the onset and recovery occur more rapidly at these muscles.24 First dorsal interosseous muscle : The monitoring of this muscle is preferable while using electromyogram (EMG). Its response exhibits good morpohology with large peak to peak amplitude and relatively little base line drift. Because the muscle lies on the dorsal side of hand the electrodes are relatively undisturbed by hand movement. The sensitivity of this muscle to nondepolarising relaxants resembles that of adductor pollicis muscle.26 Abductor digiti quiniti muscle : This muscle is less sensitive to relaxants than adductor pollicis and the time course of neuromuscular block of this muscle is similar to that of diaphragm and larynx. During recovery T4 / T1 ratio of 0.7 at adductor pollicis corresponds to 0.9 at abductor digiti quiniti. Unfortunately its response is prone to stimulus artifact and its morphology is very sensitive to electroproximity.26

(contraction of eyebrow) and orbicularis oris (contraction of the lip). The responses are similar to those of diaphragm but these muscles may be stimulated directly by the electrodes suggesting adequate neuromuscular transmission unless proper placement is achieved.28 Assessment of evoked responses to neuromuscular stimulation: (Figure 4)

Figure 4: Assessment of evoked responses to neuromuscular stimulation

Visual or tactile assessment Visual or tactile methods of evaluation of the evoked response to stimulation is the simplest means of assessment. During recovery of neuromuscular function all responses of TOF can be felt. An estimation of TOF ratio may be attempted but the method is not sensitive enough to exclude possibility of residual neuromuscular blockade. Fade is usually undetected until TOF ratio values are less than 0.5.29 Greater sensitivity for fade detection is achieved with DBS.30 Recording devices for measuring neuromuscular function Because of the unreliability of visual/tactile assessment of neuromuscular function, there has been an emerging interest in the development of quantitative devices.31 These devices measure either the compound muscle action potential (MAP) or the evoked contractile response.
Compound muscle action potential: It is the cumulative electrical signal generated by the individual action potentials of the individual muscle fibres. Electromyogram (EMG) : It records the compound MAP via recording electrodes placed near the mid portion or motor point of the muscle and it a slightly remote indifferent side. The latency of the compound MAP is the interval between stimulus artifact and evolved muscle response. The amplitude of the compound MAP is proportional to the number of muscle units that generate an MAP within the designated time interval (epoch) and this correlates with the evoked mechanical responses.32 This method is used mostly for experimental studies.

Nerves of the foot The nerves of the foot elicit responses with a sensitivity and time course similar to that of ulnar-adductor pollicis.27 The posterior tibial nerve may be stimulated as it comes behind the medial malleolus, causes plantar flexion of the great toe and foot. The peroneal nerve (stimulated behind the head of fibula) and lateral popliteal nerve elicit dorsi flexion of the foot. Facial Nerve This nerve may be stimulated as it leaves behind the stylomastoid foramen near the tragus 2-3 cms posterior to the lateral border of the orbit. The response to the stimulation is monitored commonly at the orbicularis oculi

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Evolved contractile response : It is the muscle contraction generated by the MAP in each fiber. The overall magnitude is proportional to the number of neuromuscular junctions that generate MAP. It can be quantified objectively with a mechanomyogram (force translation monitor) or accelerometer or assessed visually or manually. In the response to single twitch stimulation, the contractile response tends to parallel EMG, but during tetanic stimulation, it exhibits temporal summation.32 In addition, drugs that act subsequent to generation of MAP may also affect the contractile response. Adductor pollicis force translation monitor: This mechanomyographic device objectively quantifies the force of isometric contraction of adductor pollicis muscle in response to ulnar nerve stimulation. The force is translated into an electrical signal that can be displayed on an interfaced pressure monitor and then recorded. The key features associated with optimal use of this method include alignment of the direction of thumb movement with that of the pressure transducer, application of consistent amount of baseline muscle tension (preload), use of transducer and monitor with adequate monitoring range and zeroing of the monitor before stimulation. A preload of 200-300 gm can be used to optimally align the contractile elements (actin and myosin filaments).33 Accelerography: This technique uses a miniature piezoelectric transducer to determine the rate of angular acceleration.34 The principle is based on the constant relationship between force (F) and acceleration (a) so long as mass (m) is constant (Newtons second law, F=ma). One requirement for accelerometry is that the muscle must be able to move freely. The piezoelectric crystal is distorted by the movement of the crystal inlaid transducer which is applied to the finger and an electric current is produced with an output voltage proportional to the deformation of the crystal. This is a nonisometric measurement and there are less stringent requirements for immobilization of arm, fingers and thumb and also no preload is necessary. However, recording of tetanic responses is not possible as the movement is an essential component of accelerography. Clinical trails have shown that accelography provides T4/T1 ratios similar to those obtained by force translation.35 A number of commercially available monitors are based on this principle, TOFguard, TOFwatch (Organon Teknika), Para Graph Neuromuscular Blockade Monitor (Vital signs), Part of Datex AS/3 monitoring system (M-NMT). It is a simple method useful in operating room and in the intensive care unit.

Application of neuromuscular monitoring Getting Started Check functioning of neuromuscular monitor

Choose the appropriate nerve-muscle to be monitored Careful preparation of skin (by degreasing) Apply positive electrode proximally to prevent direct depolarization of muscle Monitoring should ideally be started before administration of neuromuscular blocker but after induction of anaesthesia Select supramaximal current (turn current slowly during repetitive single twitches until maximum plateau is achieved and then increase current level by 20%) Use of recording devices is preferable Select appropriate method of stimulation Observation and interpretation of evoked response

Clinical Application The various levels of relaxation achieved with use of neuromuscular blocking drugs occurs within well defined limits of evoked responses. Hence neuromuscular monitoring can be applied at various phases during the use of these drugs.
Onset of block and assessment of adequate intubating conditions : The latent onset time of a drug is time from injection until there is a measurable effect. The onset time is defined as the time from injection to peak effect. The measured onset time of the muscle relaxants varies according to the muscle group that has been monitored and the stimulation parameters that are being used. Until recently virtually all comparisons between drug doses and stimulation patterns have been performed at the thumb but the onset for the larynx, vocal cords and diaphragm is faster than the thumb.28 If the clinician is interested in the accurate assessment of onset time, such as during rapid sequence induction and intubation, monitoring of orbicularis oculi is perhaps more useful. When patient movement is unacceptable, trachea is intubated 30-90 seconds after response to TOF stimulation disappears. The stimulation parameters also affect the apparent onset time. Faster rates of stimulation appear to have faster onset time due to increased muscle blood flow and increased drug delivery. The onset of actual adequate intubating conditions are independent of the rate of stimulation.36

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Maintenance of block : Ideally, the goal should be to maintain the minimum depth of block that is required for surgery. Adequate surgical relaxation for abdominal surgery can be achieved with greater than 80% twitch depression, that correlates with 1 or 2 twitches present in the train of four.37 Diaphragm is relatively resistant and requires greater plasma concentration of non-depolarising muscle relaxants. When paralysis of diaphragm is required, the administration of NMB is titrated to paralysis of orbicularis oculi or suppression of post tetanic response (PTC 0 at thumb). Such a block would take considerable time to be antagonised adequately.38 Detecting reversible block : Airway patency and adequate ventilation require more than an intact diaphragm, hence it is important to assess the degree of block at a muscle that does not overestimate the rate of recovery of muscles maintaining the airway. The increased sensitivity and slower time course of the adductor pollicis muscle make this site preferable for monitoring recovery.39 The PTC may be used when no twitch response is attainable. The time to recovery of twitch response is inversely proportional to the number of PTC. When twitch response is attained TOF at 10-20 seconds interval is used. In the absence of recording device DBS may be preferable to TOF to reliably detect a fade of less than 0.3. Atracurium, vecuronium, pancuronium induced neuromuscular block is antagonised by neostigmine in 30 minutes when single twitch height is 10% of control or more or just prior to emergence of second twitch of TOF count and in 10 minutes when all the four responses to TOF stimulation are present. When zero twitches are present in the TOF the block is considered not antagonizable.40 Ensuring adequate neuromuscular function : (Table 4) Safe extubation of trachea can be performed only after adequate restoration of neuromuscular function. The TOF ratio greater than 0.75 at the thumb correlates with restoration of strength of the muscles of respiration and airway protection, vital capacity, maximum expiratory force, peak expiratory flow rate, hand grip and 5 second head lift.16,41 Eriksson et al have shown that moderate degrees of neuromuscular block decrease the chemoreceptor sensitivity to hypoxia, leading to insufficient response to a decrease in oxygen tension in blood.42 They also showed that residual block (TOF<0.9) is associated with functional impairment of pharynx and upper esophagus most probably predisposing to regurgitation and aspiration.43 The TOF ratio recorded mechanically or by EMG must exceed 0.8 or even 0.9 to exclude clinically important neuromuscular blockade. The response to neurostimulation should be assessed in correlation with clinical assessment of ventilatory function.

Table 4 : Relationship between clinical and train-of-fourevoked stimulation

Test 5-sec head or leg lift Normal grip strength Masseter All subjects uncomfortable at TOF < 0.75 TOF Equivalent 0.6 0.7 0.86

It is important that all patients be reassessed in the post-anaesthesia care unit as the incidence of residual neuromuscular blockade and recurarization may be as high as 30% in patients receiving long-acting NMBs. Persistent neuromuscular blockade contributes to postoperative pulmonary complications.4 Table 5 summarizes the application of various modes of NMJ monitoring.
Table 5 : Summary of application of neuromuscular junction monitoring
Clinical Objective Fast onset/tracheal intubation Profound blockade Adequacy of relaxation (abdominal surgery) Predicting reversible block (when no TOF response present) Detecting reversible block Detecting adequate neuromuscular function Site Orbicularis oculi Twitch Modality Target Response Single twitch or train-of-four 0 twitches

Adductor pollicis Orbicularis oculi Adductor pollicis

Post tetanic count Relaxant Train-of-four dependent Train-of-four count One to two twitches present

Adductor pollicis

Post tetanic count Relaxant dependent

Adductor pollicis

Train-of-Four count Double-burst stimulus

At least two twitches present No fade preset

Adductor pollicis

Which patients should be monitored? By the foregoing discussion, it would seem prudent to monitor NMJ in all patients receiving NMBs. Such monitoring is advisible particularly in conditions where the pharmacokinetics and pharmacodynamics of NMBs are altered significantly as listed below: 1. 2. Severe renal, liver disease Neuromuscular disorders such as myasthenia gravis, myopathies, and upper and lower motor neuron lesions

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3.

4. 5. 6.

Patients with severe pulmonary disease or marked obesity to ensure adequate recovery of skeletal muscle function Neuromuscular blockade acheived with continuous infusion of NMBs Patients receiving long-acting NMBs Patients undergoing lengthy surgical procedures

6. Ali HH, Savarese JJ. Stimulus frequency and dose-respone curve to d-tubocurarine in man. Anesthesiology 1980; 52: 36-9. 7. Ali HH, Utting JE, Gray C. Stimulus frequency in the detection of neuromuscular block in humans. Br J Anaesth 1970; 42: 967-78. 8. Lee CM. Train-of-4 quantitation of competitive neuromuscular block. Anesth Analg 1975; 54: 649 - 53. 9. Waud BE, Waud DR. The relation between the response to train-of-four stimulation and receptor occlusion during competitive neuromuscular block. Anesthesiology 1972;37:413-6. 10. Epstein RA, Epstein RM. The electromyogram and the mechanical response of indirectly stimulated muscle in anesthetized man following curarization. Anesthesiology 1973;38:212-23. 11. Savarese JJ, Ali HH, Murphy JD et al. Train-of-four nerve stimulation in the management of prolonged neuromuscular blockade following succinylcholine. Anesthesiology 1975;42:106-11. 12. Brull SJ, Silverman DG. Visual assessment of train-of-four and double burst-induced fade at submaximal stimulating currents. Anesth Analg 1991;73:627-32. 13. Lee AP. Monitoring the neuromuscular junction. Int Anesthesiol Clin 1981;19:85-93. 14. Kopman AF, Epstein RH, Flashburg MH. Use of 100-Hertz tetanus as an index of recovery from pancuronium induced non-depolarizing neuromuscular blockade. Anesth Analg 1982;61:439-41. 15. Stanec A, Heyduk J, Stanec G, Orkin LR. Tetanic fade and post-tetanic tension in the absence of neuromuscular blocking agents in anesthetized man. Anesth Analg 1978;57:102-7. 16. Ali HH, Savarese JJ, Lebowitz PW, Ramsey FM. Twitch, tetanus and train-of-four as indices of recovery from nondepolarizing neuromuscular blockade. Anesthesiology 1981;54:294-7. 17. Engbaek J, Ostergaard D, Viby-Mogensen J. Double burst stimulation (DBS): a new pattern of nerve stimulation to identify residual neuromuscular block. Br J Anaesth 1989;62:274-8. 18. Saddler JM, Bevan JC, Donati F et al. Comparison of doubleburst and train-of-four stimulation to assess neuromuscular blockade in children. Anesthesiology 1990;73:401-3. 19. Viby-Mogensen J, Howardy-Hansen P, Chraemmer-Jorgensen B et al. Post tetanic count (PTC): a new method of evaluating an intense nondepolarizing neuromuscular blockade. Anesthesiology 1981;55:458-61. 20. Eriksson LI, Lennmarken C, Staun P, Viby-Mogensen J. Use of post-tetanic count in assessment of a repetitive vecuronium-induced neuromuscular block. Br J Anaesth 1990;65:487-93. 21. Bonsu AK, Viby-Mogensen J, Fernando PU et al. Relationship of post-tetanic count and train-of-four response during intense neuromuscular blockade caused by atracurium. Br J Anaesth 1987;59:1089-92.

Limitations of neuromuscular monitoring Despite the important role of NMJ monitoring in anaesthesia practice, it is necessary to use a multifactorial approach for the following reasons: 1. Neuromuscular responses may appear normal despite persistance of receptor occupancy by NMBs. T4:T1 ratio is one even when 40-50% of the receptors are occupied. 2. Because of wide individual variability in evoked responses, some patients may exhibit weakness at TOF ratio as high as 0.8 to 0.9. 3. The established cut-off values for adequate recovery do not guarantee adequate ventilatory function or airway protection. 4. Increased skin impedence resulting from perioperative hypothermia limits the appropriate interpretation of evoked responses. Conclusion Many anaesthesiologists do not agree with extensive use of NMJ monitors and argue that patients can be managed satisfactorily without the devices. Although not included under the standards for basic anaesthetic monitoing by the American Society of Anaesthesiologists, the real value of such monitors lies in the fact that they guide the optimal management of patients receiving NMBs. References
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