MONITORING NEUROMUSCULAR FUNCTION

Details of monitoring neuromuscular function are discussed in Chapter 39 . In this section, general concepts of monitoring as they relate to the clinical use of neuromuscular blockers are presented.

Peripheral Nerve Stimulation and Clinical Tests

Monitoring of neuromuscular function after the administration of neuromuscular blocking agents is extremely important to appropriately dose these agents and to better guarantee patient safety.^{[40] [41]} In the operating room or the ICU, the depth of neuromuscular blockade is typically monitored by observing the response of any superficially located neuromuscular unit to stimulation. Most commonly, contraction of the adductor pollicis associated with stimulation of the ulnar nerve, either at the wrist or at the elbow, is monitored. In certain circumstances, depending on patient positioning where access to the patient's arms may be limited or because of the nature of the injury, the peroneal nerve or the facial nerve may be monitored.

The pattern of response to TOF stimulation (four stimuli delivered over a period of 2 seconds) or a tetanic stimulus varies with the type of neuromuscular blocker administered because the two relaxant types, depolarizing and nondepolarizing, have different mechanisms of action. With a complete block, no response to either mode of stimulation should be seen. However, during partial neuromuscular blockade, different responses are seen to these modes of stimulation, depending on the agent administered. Nondepolarizing neuromuscular blocking agents are competitive inhibitors of the acetylcholine receptor—they compete with acetylcholine for the active, or binding, sites on the α-subunits of the receptor. With repetitive or intense stimulation, the response to stimulation fades over time because of a decrease in the amount of acetylcholine released from the prejunctional nerve terminal with successive stimuli. The fourth response to a TOF stimulus is decreased relative to the first response ( Fig. 13-2 ) because the lesser amount of acetylcholine released into the synaptic cleft with the fourth stimulus cannot overcome the competitive block as readily. Similarly, fade is seen in the response to tetanic stimuli when a partial nondepolarizing neuromuscular block is present. During neuromuscular blockade with nondepolarizing agents, if one administers a TOF stimulus shortly after administering a tetanic stimulus, the response to stimulation is augmented and neuromuscular function appears stronger than it did just a couple of minutes earlier. This presumably occurs because with the tetanic stimuli, acetylcholine is mobilized toward the presynaptic portion of the nerve terminal and then, with subsequent stimulation (TOF), an increased amount of acetylcholine is released into the synaptic cleft and the block imposed by the nondepolarizing agent is

Figure 13-2 Schematic representation of the onset of a neuromuscular block after administration of a nondepolarizing neuromuscular blocking agent at the arrow. Neuromuscular function is monitored with repetitive train-of-four (TOF) stimuli (four stimuli of 0.5-msec duration administered over a period of 2 seconds). Note the presence of fade in the response to TOF stimulation.

Figure 13-3 Schematic representation of the onset of a neuromuscular block after administration of a depolarizing neuromuscular blocking agent at the arrow. Neuromuscular function is monitored with repetitive train-of-four stimuli (four stimuli of 0.5-msec duration administered over a period of 2 seconds).

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Donati and colleagues^[46] and Pansard and associates^[47] have demonstrated that neuromuscular blockade develops faster in centrally located muscles, such as the larynx, the jaw, and the diaphragm, than in more peripherally located muscles, such as the adductor pollicis. In addition to developing more quickly, neuromuscular blockade in these regions, at a given dose, is less profound and recovers more quickly ( Fig. 13-4 ) (for details see the section "Neuromuscular Blockers and Tracheal Intubation").^[46] Consequently, the choice of monitoring site is important.

To determine the depth of block during maintenance and recovery of neuromuscular function, the response of the adductor pollicis to stimulation of the ulnar nerve should be monitored. If recovery in this neuromuscular unit is complete, recovery in the musculature of the airway should also be complete.^[46]

Peripheral nerve stimulation can be used to determine both the magnitude and the depth of neuromuscular blockade. However, the degree of neuromuscular block must be assessed cautiously. Because there is such a wide margin of safety as regards neuromuscular function, with a large number of acetylcholine receptors having to be blocked before weakness becomes detectable, the reduction in contractile response to peripheral nerve stimulation is not proportional to the action of neuromuscular blockers at the receptor. Waud and Waud^[48] demonstrated that the twitch response of the tibialis anterior muscle of the cat in response to a single supramaximal stimulus is not reduced unless more than 70% of the receptors are occupied by a nondepolarizing neuromuscular blocker. Twitch is completely eliminated when 90% of the receptors are occupied. Three questions can be answered by observing the response to peripheral nerve stimulation: (1) is the neuromuscular blockade adequate? (2) is the neuromuscular blockade excessive? and (3) can the neuromuscular blockade be antagonized?

Muscle contraction is an all-or-none phenomenon. Each fiber either contracts maximally or does not contract at all. Therefore,

Figure 13-4 Evolution of neuromuscular blockade in the larynx and thumb (adductor pollicis) after 0.07 mg/kg vecuronium. Onset and recovery from the block occur more rapidly in the larynx. (Redrawn from Donati F, Meistelman C, Plaud B: Vecuronium neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis. Anesthesiology 74:833–837, 1991.)

Because the interaction of nondepolarizing neuromuscular blockers with acetylcholine receptor binding sites is competitive, neuromuscular blockade can be overcome by increasing—or intensified by reducing—the concentration of acetylcholine. This concept is important in clinical monitoring of neuromuscular blockade. Another important concept is the economy of acetylcholine synthesis, storage, and release. The quantity of acetylcholine released with each nerve action potential is inversely proportional to the number of action potentials reaching the nerve terminal per unit time, or the stimulus frequency. The depth of blockade of evoked neuromuscular responses in the presence of nondepolarizing neuromuscular blockers is directly proportional to the stimulus frequency.

The onset of neuromuscular blockade should be monitored with either single twitch stimuli or TOF stimuli because one is looking for ablation of the twitch response, or its maximal suppression, to determine onset of the block. The depth of block during maintenance of blockade and recovery should be monitored with repeated TOF stimuli, where depending on the surgery and the type of anesthetic administered, the anesthesiologist may want to maintain deeper levels of neuromuscular blockade (one or two twitches in response to TOF stimuli) or lesser degrees of blockade (three to four twitches in response to TOF stimuli). When determining the depth of block to maintain during the course of an anesthetic, it is important to remember that a deep volatile anesthetic will provide some degree of muscle relaxation and patient immobility and that volatile anesthetics potentiate nondepolarizing neuromuscular blockers. Similarly, recovery of neuromuscular function should be monitored with TOF stimuli. Once four responses to stimulation are detectable and fade in the response is no longer detectable, the TOF ratio (the strength of the fourth response in comparison to the strength of the first response to stimulation) may be 40% to 100%. It is difficult to more reliably detect fade in the TOF response^{[48] [49]}

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In addition to using monitors of muscle strength, clinical indicators of adequacy of return of neuromuscular function should also be sought. Such clinical tests include a 5-second head lift, handgrip, and in a patient unable to cooperate with simple commands, the ability to bend the legs up off the operating room table. A successful head lift is one done from a flat surface, unaided and maintained for a full 5 seconds. Pavlin and coworkers^[53] have shown that if patients can successfully perform a head lift, their maximum inspiratory force is approximately -55 cm H₂ O, and if they can lift their legs off a flat surface, their maximum inspiratory force is -50 cm H₂ O. With a strong handgrip, clinicians should not be able to pull their fingers from the patient's grip. Even though these tests have long been the mainstay of clinical tests of neuromuscular function, they can be accomplished over a wide range of TOF ratios and must be used with caution. As described by Kopman and coauthors,^[54] volunteers with TOF ratios as low as 0.5 are capable of maintaining a 5-second head lift and having a strong handgrip. The ability of patients to oppose their incisors and maintain a tongue blade between them appears to be a more sensitive indicator of the adequacy of muscle strength inasmuch as volunteers were unable to perform this task until their TOF ratios had returned to 0.85. In patients, however, even this ability does not seem to be a sensitive indicator of residual neuromuscular block.^[55]

Monitors of respiratory function do not reliably indicate return of muscle strength and function to baseline. Tidal volume is inadequate as a monitor of the adequacy of muscle strength because it is more likely to reflect recovery in the centrally located muscles of respiration and is dependent on diaphragmatic movement only. With a tidal volume of at least 5 mL/kg, 80% of acetylcholine receptors may still be occupied by nondepolarizing neuromuscular blocking drugs. Head lift and handgrip may be 38% and 48% of control, respectively, when both inspiratory and expiratory flow rates are more than 90% of control.^[56] Furthermore, inspiratory force may be only 70% of control when vital capacity and the expiratory flow rate are greater than 90% of control values.^[57]