Making adequate assessments of the depth of paralysis and the return of spontaneous ventilation are critical to effective NMB.

In the US health care system, the severity of illness seen in critical care units continues to rise as increasingly complex procedures and therapies are undertaken to diagnose and treat the disease processes of critically ill patients. The use of neuromuscular blockade (NMB) medications is a valuable adjunct in the control of ventilation and in the provision of patient care. While the rate of complications associated with the use of NMB medications is low, adequate assessment of the depth of paralysis and the return of spontaneous ventilation requires constant vigilance. Resolving complications related to NMB use may require a prolonged course of mechanical ventilation and may incur unanticipated costs related to the higher level of care provided to the patient. Not only can negative consequences occur during NMB, but they can sometimes have effects that compromise the patient’s health in the days following the attempt to wean him or her from ventilator dependency.

Monitoring the level of blockade may allow the clinician to provide improved ventilator management for the paralyzed patient. Several techniques are available for monitoring the depth of NMB, and some of these techniques provide quantification of the depth of paralysis.

Neuromuscular Function and NMB Agents
Nerves resemble elongated bags of salty water. The outside of a nerve is positively charged (polarized). That charge is lost when the top of a nerve cell is stimulated. The resulting wave of depolarization runs down the cell from the brain to the muscle. The nerve swells near the muscle at the neuromuscular junction. The nerve cell releases acetylcholine into the gap between the nerve and the muscle.

A muscle has a polarized membrane surrounding it; special receptors are built into this membrane. When acetylcholine attaches to a receptor, the membrane is depolarized. The wave of depolarization runs over the muscle fiber and causes it to contract.

Anesthesiologists use NMB agents to keep patients from moving during surgery and increase the ease of intubation. These muscle relaxants are also used when it is necessary to take over a patient’s breathing or when the muscles of the abdomen need to be relaxed to enable the surgeon to perform a procedure. NMB agents are used in critical care areas for the same reasons. It is the blocking of transmissions across the neuromuscular junction, performed by muscle relaxants, that produces muscle relaxation. The acetylcholine released by the nerve terminal can no longer cause depolarization of the muscle membrane.

NMB agents fall into two categories: depolarizing and nondepolarizing. With depolarizing agents such as succinylcholine chloride, the physiological conduction of acetylcholine across the neuromuscular junction is prevented by depolarization of the motor end plate. Nondepolarizing relaxants such as tubocurarine chloride do not cause depolarization; they occupy the specific receptor sites on the motor end plate. This prevents acetylcholine from attaching to the receptor sites. Although all muscle relaxants act on the neuromuscular junction, the modes and durations of action (and intensity of blockade) differ for various agents.

Potential Complications
There are a number of factors that can influence the morbidity and mortality related to NMB. These include patient selection, type of procedure, type of NMB agent used, and NMB monitoring equipment.

Many causes of morbidity and mortality during NMB administration are linked to the respiratory system. For intubated patients, there is always the risk of undetected esophageal intubation, with a resultant risk of hypoxemia. This has been addressed in recent years through improved monitoring (pulse oximetry and capnography) and backup airway management techniques. Other complications, which may depend on the blocking agent used, can include laryngospasm; bronchospasm; aspiration; intubation injuries to the teeth, lips, pharynx, esophagus, larynx, or trachea; pulmonary edema; respiratory arrest; cardiovascular problems; hypotension; anaphylaxis; and prolonged paralysis.1,2

Clinical conditions that can precipitate complications during and after NMB include cardiovascular problems such as myocardial ischemia/infarction, cardiac failure, or cardiac arrest (which may be secondary to a respiratory problem); emboli due to clots, air, or orthopedic stimuli; and hypotension due to undetected hypovolemia or massive hemorrhage.

One of the most serious complications that can occur with NMB is malignant hyperthermia, a potentially fatal hypermetabolic state of skeletal muscle. Malignant hyperthermia frequently presents as an intractable spasm of the jaw (masseter) muscles that may progress to generalized rigidity, increased oxygen demand, tachycardia, tachypnea, and profound hyperpyrexia. A successful outcome depends on recognition of early signs such as jaw-muscle spasm, acidosis, and failure of tachycardia to respond to deepening anesthesia. Malignant hyperthermia occurs more commonly in response to depolarizing muscle relaxants.

Response Assessment
The use of NMB agents in the critical care arena is controversial, but widely accepted.3 For newer agents, indications for use have expanded. Along with this expanded use, however, goes an even greater need to assess the patient’s response to these agents.4

Clinical assessment of NMB is possible, but is limited, in practice, due to sedation, reduced level of consciousness, and other factors. Several clinical signs manifest themselves; in order of increasing blockade, they are:

• diplopia or weakness of the extraocular muscles,
• a perception of weakness or heaviness,
• difficulty swallowing,
• inability to sustain lifting of the head,
• decreased peak inspiratory force,
• obvious muscular weakness,
• poor grip strength,
• decreased vital capacity or inspiratory flow rate,
• respiratory insufficiency, and
• diaphragmatic paralysis

Clinical assessment of the patient will provide the RCP with substantial information about the patient’s level of paralysis, but this information may not be adequate, in many situations.5 Beyond clinical assessment, more quantifiable forms of NMB monitoring involve electrical nerve-stimulation devices of various kinds.6,7 These devices include small, portable stimulators and modules as part of comprehensive cardiopulmonary monitors. The advantages of using peripheral nerve stimulators in the critical care environment include cost savings,8 reduced administration of NMB agents,9 and a reduction in neuromuscular dysfunction.10

Prior to the use of any nerve stimulator, the patient must receive adequate sedation and pain control. The negative electrode of the nerve stimulator is attached as closely as possible to the skin surface near a nerve (commonly, the ulnar nerve at the wrist or elbow). The facial nerve can be used if there is no access to the hands. The other electrode can be placed anywhere along the line of the nerve, and is typically positioned halfway along the forearm. The clinician then assesses the amount or strength of movement in muscles (usually in the thumb) supplied by that nerve.

The outside of a resting nerve is polarized; if electrons are added to the outside, they will neutralize the positive charge. A nerve stimulator works by supplying negative electrons, causing a wave of depolarization to wash down the nerve. The number of electrons supplied per stimulus equals the current.

To ensure that the nerve is completely depolarized, the stimulating current is increased until the muscular response does not increase any more. The current level is then increased another 10% to provide supramaximal stimulus. At this point, it is assumed that the nerve supplying the muscle is completely depolarized. As a result, the muscle must be maximally stimulated by the nerve. The muscle contraction (twitch) that results must also be maximal. The amount or strength of movement is called the twitch height (from the height of the resulting tracing seen on a recorder). To allow comparison of twitches, it is essential for the current to remain constant, thus ensuring that the nerve is always completely depolarized.

Peripheral nerve stimulators are battery-operated devices. Their output may vary according to the battery power supplied to the electrodes. This reduced level of electrical stimulus may lead the clinician to the incorrect conclusion that the patient is adequately relaxed. A controlled NMB (accelerometer) monitor, in contrast, delivers consistent levels of electrical stimulus to the electrode site and provides automated documentation.

The information obtained through NMB monitoring assists the RCP in delivering improved care in several ways. It facilitates adjusting the timing and dosage of NMB medications to achieve optimal effect. The duration of action at the synapse varies considerably, depending on the medication chosen by the ordering physician. Avoiding accidental recovery (with its potential to produce patient injury or an increase in the work of breathing) is a key advantage of the documented, repeatable assessment of NMB. Determining the appropriate time to reverse the relaxant and extubate the patient is also vital to successful NMB.

In addition, NMB monitoring helps the RCP to decrease avoidable side effects such as spontaneous (and potentially dangerous) movement, prolonged paralysis, expensive overutilization of NMB agents, and a delay in recovering from drug and/or metabolite accumulation.The clinical use of peripheral nerve stimulators to assess NMB has become more widespread because they permit titration of the drug dose to produce the desired effect, allowing more accurate prediction of the clinical degree of paralysis than any other means in anesthetized patients (particularly where deep levels of paralysis are required). Peripheral nerve stimulators provide the clinician with both tactile and visual responses to stimuli, and can display graphical as well as numerical information. Peripheral nerve stimulators do, however, have their shortcomings. In one study, the authors stated, “When full recovery of neuromuscular function is critical, neither visual nor tactile assessment from any form of peripheral nerve stimulator tested is adequate.”11

Stimuli Provided by Nerve Stimulators
There are four primary stimuli provided by nerve stimulators: single twitch, train of four, post-tetanic count, and double burst.

The single-twitch stimulus is the simplest type. A fixed current is used to stimulate the nerve for a brief period. This is known as a square-wave stimulus. If more than 80% of the receptors are blocked, there will be a decrease in the height of the twitch (or no twitch at all). The amount of movement in response to a supramaximal stimulus before any relaxant is given is known as the supramaximal response. Successive twitches are often reported as a percentage of this control height; for example, a patient can have NMB drugs reversed when the first twitch reaches 20% of the control value. A control twitch must be measured before any relaxant has been given.

Emergency procedures such as rapid-sequence intubation may require quick administration of the muscle relaxant, so the calibration step must be performed on patients before they are sedated and given pain medications. This stimulus may be painful for patients. The subjective measurement of the twitch response can become an issue, but the use of assessment technology allows objective measurement of the patient’s response to the controlled stimulus.

To aid in surmounting the problem of subjective assessment of the height of the control twitch, the train-of-four method was developed. Four twitches are automatically delivered at 0.5-second intervals. The first twitch in the train can be used as the control. Each successive response to a stimulus becomes lower as the acetylcholine in the nerve terminal is depleted. After a pause of 30 seconds, the acetylcholine in the nerve terminal will have built up again, so the test can be repeated.

In addition to estimating the fading of twitches in the train-of-four test, it is also useful simply to count the twitches. Fewer stimuli cross the neuromuscular junction as the block becomes deeper. For most patients, a block with a response of two twitches is adequate for controlling ventilation. As the level of neuromuscular blockade deepens and only one twitch is recognized by the monitor or clinician, the patient may still be able to move slightly. If relaxant is administered at doses adequate to eliminate all twitches, the RCP will no longer be able to determine the level of relaxation.

At the other end of the relaxant scale, the clinician may need to ensure that the neuromuscular block has worn off. Fading on the train-of-four test can be difficult to detect in a minor block without an NMB monitor. The middle two twitches make it difficult to compare the first and the last. Double-burst stimulation consists of two sets of twitches that are separated by a brief interval to improve the perception of fading. The first twitches and the brief pause are designed to prevent facilitation occurring between the first and second bursts.

The post-tetanic count was developed to allow the control of deep blockade. After a period of rapid stimulation (tetany), the nerve cells gear up for action. After a brief pause, the twitch height will be increased above baseline for that degree of block. Not only the height, but the number of twitches increases. The NMB agent is administered via intravenous line until no twitches at all are visible or tracked by the monitor. A burst of tetany is given, followed by a pause and then by one stimulus every second for 10 seconds. The clinician observes the number of visible twitches, or the monitor can objectively assess the response. When only one or two twitches are visible, the block is very deep.

If possible, the patient should be assessed prior to receiving NMB medication to obtain a baseline level and ensure proper placement of electrode pads. Initially, and after changes in dosage, nerve stimulation should be assessed every 1 to 2 hours until the desired level of relaxation is achieved. At that point, the level of paralysis should be assessed at intervals according to the institution’s protocols and policies. Controlled methods of NMB monitoring can allow this assessment to be performed automatically at preset intervals, with the monitor also recording physiological parameters. The monitor can also alert the clinician to the earlier-than-expected return of spontaneous muscle control. The physician should determine, daily, the need for NMB and its proper level (defined as the desired number of twitches on the train-of-four test). The ordering physician is to be consulted if the level of NMB varies from this target level.

Types of Nerve Stimulators
Constant-voltage nerve stimulators are relatively easy and inexpensive to make. Unfortunately, if the voltage remains constant, current decreases when resistance increases and the nerve may not be completely stimulated. The muscle contraction will then be depressed. The RCP may falsely conclude that the NMB drug is still active, resulting in patient movement, increases in airway pressure, and asynchronous ventilation.

Increasing resistance at the electrodes is countered by an increase in the voltage delivered by constant-current nerve stimulators. As a result, the stimulation of the nerve remains constant. Any change noted in response is, therefore, occurring at the neuromuscular junction or in the muscle itself.

Quantifiable NMB monitoring uses mechanomyography (in the form of an accelerometer) to quantify the muscular response to a known level of nerve stimulation objectively.12 The accelerometer produces an electrical signal when there is muscular response to the nerve stimulation. The two stimulating electrodes are placed above the ulnar nerve. The sensor is positioned as directed by the manufacturer (typically, between the index finger and the thumb) and the sensor is taped in the center to prevent movement artifacts. One of the key advantages of the accelerometer is the ability to record the patient’s response to the stimulus automatically on a patient monitor.

Policies and Procedures
All clinicians should have clearly defined responsibilities for patient monitoring and care during the period of ventilator dependency and paralysis. Hospitals have developed guidelines for patient monitoring, NMB, and NMB monitoring based on the complexity of the procedure. Trained personnel should be available for the administration and monitoring of the effects of NMB, and staff for airway management should be immediately available. Patient monitoring during the procedure requires documentation of the dosage and timing of NMB, and of the patient’s response to it, throughout the critical care stay.

An effective multidisciplinary plan to manage paralysis in critical care areas helps ensure a team approach, coordinating the efforts of nurses, physicians, and RCPs. Team members and team management must be prepared for worst-case scenarios, and must have plans in place for resolving problems that may occur during paralysis. These plans must cover patients who cannot be ventilated or intubated and paralyzed patients who become extubated.

Monitoring the patient’s electrocardiogram, heart rate, blood pressure, temperature, oxygen saturation (using pulse oximetry), and end-tidal carbon dioxide as required constitutes the standard of care for procedures that require NMB. Patients requiring sedation and analgesics are observed using the monitors deemed appropriate by the clinician.

Conclusion
Adequate assessments of the depth of paralysis and the return of spontaneous ventilation are critical to effective NMB and to the avoidance of complications or adverse effects. While clinical assessment of the effects of NMB is possible for some patients, nerve stimulators with objective measurement technology provide more specific, quantifiable assessment for a broader range of patients. RCPs who are knowledgeable and skilled in the use of nerve stimulators provide a valuable component of NMB care.

Dan Hatlestad is a public speaker and trainer, Littleton, Colo.

References
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