Neuromuscular monitoring

Abstract

Neuromuscular Monitoring A method of neuromuscular monitoring and corresponding apparatus for determining the effectiveness of a neuromuscular block. The method comprises inserting an electrode into a muscle of a mammalian subject, wherein the muscle has a singular branch of innervation, and the electrode extends to an innervation end point. The method is characterised by monitoring a sub-threshold potential at a neuromuscular junction of the muscle.

Description

[0001] NEUROMUSCULAR MONITORING

[0002] FIELD

[0003]

[0001] Disclosed are neuromuscular monitoring methods, and associated apparatus.

[0004] BACKGROUND

[0005]

[0002] The use of neuromuscular monitoring, also known as neuromuscular function monitoring, to assist anaesthetists during administration of paralytic agents is recommended for patient protection. Neuromuscular monitoring techniques can be subdivided into methods that measure electrical response to an applied stimulus in the form of compound muscle action potential, and those that monitor a contractile response of a muscle or muscle group to an applied stimulus. Measurement of the electrical response is referred to as electromyography, whereas the mechanical response to stimulation of the muscle can be measured using mechanomyography, kinemyography and acceleromyography techniques.

[0006]

[0003] Across the range of neuromuscular monitoring methods, the primary aim is to determine the extent of the effect of a neuromuscular blocking agent on a patient. An increase in sensitivity is desirable to make the depth of the neuromuscular blocking effect easier to monitor, so that a desired state of paralysis can be achieved. However, other factors are also relevant, such as ease and cost of manufacture, ease of application of monitoring equipment to a patient, and the ease of integration into related surgical and monitoring equipment which is present in surgical theatres.

[0007] SUMMARY

[0008]

[0004] In one aspect there is provided a method of neuromuscular monitoring for determining the effectiveness of a neuromuscular block, the method comprising: inserting an electrode into a muscle of a mammalian subject, wherein the muscle has a singular branch of innervation, and the electrode extends to an innervation end point, and characterised by monitoring a subthreshold potential at a neuromuscular junction of the muscle as a result of proximal nerve stimulation.

[0009]

[0005] Rather than neuromuscular monitoring that requires activation of a muscle to determine the effectiveness of a neuromuscular block, a relatively sensitive determination can be made by considering the potential at the neuromuscular junction(s) when this is the singular innervation route for the muscle.

[0010]

[0006] In one example, the method comprises stimulating the nerve that provides the singular branch of innervation. In one example, the method comprises providing a peripheral nerve stimulator by which a stimulus is provided. In one example, the method uses an electrode and integrated peripheral nerve stimulator. This facilitates insertion of the electrode such that an appropriate nerve stimulus can be provided. In one example, the electrode is a single use component, and the method comprises disposing of the electrode after use. In one example, the electrode and peripheral nerve stimulator comprise the only components that contact the subject, and comprise an integrated single use component.

[0011]

[0007] In one example, the method further comprises stimulating the nerve that provides the singular branch of innervation, and using the electrode to monitor the sub-threshold potential at a neuromuscular junction of the muscle in response to the stimulus.

[0012]

[0008] In one example, the method comprises stimulating the nerve with a series of stimuli. In one example, the method comprises stimulating the nerve with a series of pulses. In one example, the series of pulses comprises a regular pulse train. In one example, the method comprises stimulating the nerve with a series of single pulses. In one example, the method comprises stimulating the nerve with a series of grouped pulses. The pulses for example may be provided at regular intervals, or in some other regular pattern, or randomly. In one example, the method comprises providing a minimum relaxation period between stimuli. In one example, the pulses are separated by 30 seconds, or 45 seconds or more. In one example, the pulses are separated by one minute, by two minutes or by more than two minutes.

[0013]

[0009] In one example, the method is commenced before administration of a neuromuscular block. In one example, the method is performed from commencement of a neuromuscular block and continues while the neuromuscular block is in place. In one example, the method is performed throughout the duration of a neuromuscular block, for example until the administration of a neuromuscular block reversal agent. In one example, the method is performed throughout the duration of a neuromuscular block, for example until the effect of the neuromuscular block is ended, for example until the subject has been extubated and / or is fully alert.

[0014]

[0010] In one example, the method comprises processing the signal received from the electrode, to produce an indication of the effectiveness of a neuromuscular block. In one example, the processing of the signal received from the electrode comprises one or more of: amplifying the signal; filtering; removing common mode noise. In one example, the method comprises AD (analogue-to-digital) converting of the signal received from the electrode.

[0015]

[0011] In one example, the method comprises outputting an indication corresponding to the effectiveness of the neuromuscular block. In one example, the method comprises outputting an indication of the effectiveness of the neuromuscular block in the form of a visual indication, such as a visual indication on a display.

[0016]

[0012] In one example, the method comprises outputting an indication corresponding to the change of effectiveness of the neuromuscular block. In one example, the method comprises outputting a graphical representation of the effectiveness of the neuromuscular block over time. In one example, the method comprises outputting an indication of whether the effectiveness of the neuromuscular block is increasing or decreasing.

[0013] In one example, the method comprises determining a target range for the effectiveness of the neuromuscular block, and activating an alarm if the effectiveness of the neuromuscular block is not within the target range.

[0017]

[0014] In one example, the method comprises activating an alarm if the effectiveness of the neuromuscular block is determined to be below a lower threshold corresponding to too deep a block. In one example, the method comprises activating an alarm if the effectiveness of the neuromuscular block is determined to be above an upper threshold corresponding to too shallow a block. Herein, depth of block refers to the degree of blocking effect, with a deeper block corresponding to a greater degree of blocking effect and correspondingly a shallower block corresponding to a lesser degree of blocking effect.

[0018]

[0015] In one example, activating an alarm comprises activating a visual alarm, such as a warning light. The warning light may be a flashing light. In one example, the visual alarm comprises a warning symbol that appears on a display. In one example, the visual alarm comprises a written notification that appears on a display. In one example, activating an alarm comprises outputting an audible alarm, for example a beep, a siren, or other such sound.

[0019]

[0016] In one example, the method comprises outputting an indication corresponding to the effectiveness of the neuromuscular block as part of a feedback control system for administering a neuromuscular blocking agent to a subject. In one example, the method comprises outputting an indication corresponding to the effectiveness of the neuromuscular block as part of a feedback control system for administering a neuromuscular block reversal agent to a subject.

[0020]

[0017] In one example, the method comprises determining, based on the effectiveness of the neuromuscular block, the need to administer additional neuromuscular blocking agent to a subject. In one example, the method comprises determining, based on the effectiveness of the neuromuscular block, the need to administer a neuromuscular block reversal agent to a subject.

[0021]

[0018] In one example, the method comprises administering, based on the determined effectiveness of the neuromuscular block being too shallow a block, additional neuromuscular blocking agent to a subject. In one example, the method comprises administering, based on the determined effectiveness of the neuromuscular block being too deep a block, a reduced amount of neuromuscular blocking agent thereafter, or administering a neuromuscular block reversal agent.

[0022]

[0019] In one example, the administering is carried out by a human. For example, a doctor, nurse, anaesthesiologist or other such individual responsible for monitoring sedation of the subject.

[0023]

[0020] In one example, the administering is carried out automatically as part of the feedback control system. In one example, the method comprises administering automatically to keep the level of the neuromuscular block in a target range for the effectiveness of the neuromuscular block, as part of a feedback control system. In one example, the feedback control system comprises an adaptive gain in the feedback loop. In one example the adaptive gain in the feedback loop is determined according to the previous response of a subject to administration of a neuromuscular blocking agent. In one example, the adaptive gain in the feedback loop is determined by Al or machine learning utilising data models to predict response trends. In this example, the data models may include stratified data based on, for example, age, sex and / or BMI. In these examples, the adaptive gain is used to determine the appropriate amount of neuromuscular blocking agent or neuromuscular block reversal agent to maintain the level of neuromuscular block in the target range.

[0024]

[0021] In one example, the method is conducted during perioperative or intraoperative care, such as during perioperative or intraoperative care of a subject, such as a human subject.

[0025]

[0022] In one example, the muscle being monitored is a muscle in the hand of a subject. In one example, the muscle being monitored is a thenar muscle. In one example, the muscle being monitored is one of: the opponens pollicis, the abductor pollicis brevis, and the flexor pollicis brevis. In one example, the muscle being monitored is a superficial muscle. In one example, the muscle being monitored is the abductor pollicis brevis. In one example, the muscle being monitored is innervated by the median nerve. In one example, the muscle being monitored is innervated by the recurrent branch of the median nerve. In mammalian subjects, these muscles are readily accessible, and provide a suitable singular branch of innervation.

[0026]

[0023] In one example, the sub-threshold potential is the threshold at the neuromuscular junction between the resting potential and the threshold value at which recruitment cascade of muscle fibres occurs. Typically, resting potential of skeletal muscle is -75mV or a greater negative potential, with the threshold being closer to OV. In one example, the sub-threshold potential being monitored is a potential in the range of -70mV to -50mV. In one example, the sub-threshold potential being monitored at the neuromuscular junction is a potential in the range of -55mV to - 50mV. These values are appropriate to thenar muscles, in particular the abductor pollicis brevis in human subjects. In one example, the method comprises determining a resting potential, and comparing the monitored potential thereto.

[0027]

[0024] In one example, the method comprises inserting a bipolar electrode. In one example, the electrode comprises a reference pole and a sense pole. In one example, the electrode comprises a plurality of sense poles, for measuring potential relative to a reference pole. In one example, the reference pole is referenced to a ground or earth potential.

[0028]

[0025] In one example, the electrode comprises a plurality of second poles that are spaced apart from one another, for example at equal spacing from one another. In one example, the second poles are arranged around the reference pole. In one example, the second poles are arranged in a plane. In one example, the second poles are arranged at a common distance from the reference pole, for example at the same offset from the reference pole. In one example, the second poles are arranged at a common distance from the end of the electrode. In one example, the reference pole is arranged centrally with respect to the second poles. In one example, the reference pole extends to a point, for example the extreme point, or end of the electrode. In one example, the reference pole comprises a tapered form, for example comprises a generally conical shape, for example a shape that is narrower toward the end of the electrode. In one example, the second pole(s) are arranged with the reference pole to form a tapered form. In one example the reference pole tapers at a first taper angle, and the second pole(s) taper at a second taper angle. In one example the second taper angle is greater than the first taper angle, i.e., the electrode gets wider more quickly in the region of the second pole(s), for example.

[0029]

[0026] In one example, the second pole(s) each comprise a separate electrical path for a sensed potential, with reference to the reference pole. In one example, the second pole(s) are formed from individually insulated wires. In one example, the second pole(s) are formed from wires that are wrapped around the reference pole, for example separately insulated wires. In one example, the second pole(s) are insulated, away from their ends, in parylene or another sufficiently insulating material. In one example, the wires are wrapped around the reference pole, spirally progressing away from the free end of the electrode. In one example, the second poles are interwound with one another. In one example, the electrode comprises an even number of second poles, for example 2 second poles. In one example, the electrode comprises a 2An electrodes, for example 4, 8, 16, 32, or 64, or more.

[0030]

[0027] In one example, the electrode comprises a sensing region at the end thereof. In one example, the method comprises positioning the electrode such that the sensing region is at the neuromuscular junction(s).

[0031]

[0028] In one example, the method comprises positioning the reference pole at the neuromuscular junction(s).

[0032]

[0029] In one example, the method comprises positioning the end of the electrode at the neuromuscular junction(s).

[0033]

[0030] In one example, the sensing region comprises a three-dimensional region between the reference pole and the second pole(s).

[0034]

[0031] In one example the electrode comprises tungsten, for example the reference electrode comprises a tungsten needle. In one example, away from the end, the reference electrode is covered in insulating material, for example parylene.

[0035]

[0032] In one example, the electrode comprises a needle, for example a hypodermic needle, for example, a concentric needle electrode, for example, a cannula.

[0036]

[0033] In one example, the one or other of the reference pole and the electrode extends through the needle such that one of said poles is in an aperture at the end of the needle. That is to say, the pole is exposed on the external surface of the needle at the end of the needle.

[0034] In one example, the needle is coated with a conductive substance that is ablated to form multiple helical paths which are then coated with an insulating coating. In one example, the insulating coating comprises parylene. In one example, the insulating coating is selectively ablated to form the second poles along the length of the electrode.

[0037]

[0035] In one aspect, there is provided a neuromuscular monitoring apparatus for determining the effectiveness of a neuromuscular block, the apparatus comprising an electrode for inserting into a muscle of a mammalian subject, the muscle having a singular branch of innervation, and characterised by a controller to monitor a sub-threshold potential at the neuromuscular junction of the muscle.

[0038]

[0036] In one example, the apparatus comprises a peripheral nerve stimulator. In one example, the electrode and peripheral nerve stimulator are integrated with one another. In one example, the electrode and peripheral nerve stimulator comprise an integrated single use component. In one example, the electrode and peripheral nerve stimulator are integrated on a carrier sheet. In one example, the carrier sheet comprises an adhesive surface, to adhere to a subject in use. In one example, the electrode and peripheral nerve stimulator each comprise electrical connectors for coupling to the controller. In one example, the electrical connectors are also suitably integrated into a single use component, such as an adherent sheet.

[0039]

[0037] In one example, the controller is arranged to provide a stimulation signal to stimulate the nerve that provides the singular branch of innervation, and to monitor the sub-threshold potential at a neuromuscular junction of the muscle in response to the stimulus, at the electrode.

[0040]

[0038] In one example, the controller is arranged to provide a stimulation signal to stimulate the nerve with a series of stimuli. In one example, the stimulation signal comprises a series of pulses. In one example, the series of pulses comprises a regular pulse train. In one example, the stimulation signal comprises a series of single pulses. In one example, the stimulation signal comprises a series of grouped pulses. The pulses for example may be provided at regular intervals, or in some other regular pattern, or randomly. In one example, the controller is arranged to provide a minimum relaxation period between stimuli. In one example, the pulses are separated by 30 seconds, or 45 seconds or more. In one example, the pulses are separated by one minute, two minutes, or more than two minutes.

[0041]

[0039] In one example, the controller is arranged to process the signal received from the electrode, to produce an indication of the effectiveness of a neuromuscular block. In one example, the processing of the signal received from the electrode comprises one or more of: amplifying the signal; filtering; removing common mode noise. In one example, the controller is arranged to AD convert the signal received from the electrode.

[0042]

[0040] In one example, the controller is arranged to output an indication corresponding to the effectiveness of the neuromuscular block. In one example, the controller comprises a display, and is arranged to output an indication of the effectiveness of the neuromuscular block in the form of a visual indication on the display.

[0043]

[0041] In one example, the controller is arranged to output an indication corresponding to the change of effectiveness of the neuromuscular block. In one example, the controller is arranged to output a graphical representation of the effectiveness of the neuromuscular block over time. In one example, the controller is arranged to output an indication of whether the effectiveness of the neuromuscular block is increasing or decreasing.

[0044]

[0042] In one example, the controller is arranged to determine and / or monitor a target range for the effectiveness of the neuromuscular block, and activate an alarm if the effectiveness of the neuromuscular block is not within the target range.

[0045]

[0043] In one example, the controller is arranged to activate an alarm if the effectiveness of the neuromuscular block is determined to be below a lower bound threshold corresponding to too deep a block. In one example, the controller is arranged to activate an alarm if the effectiveness of the neuromuscular block is determined to be above an upper threshold corresponding to too shallow a block.

[0046]

[0044] In one example, activating an alarm comprises activating a visual alarm, such as a warning light of the controller. The warning light may be a flashing light. In one example, the visual alarm comprises a warning symbol that appears on the display. In one example, the visual alarm comprises a written notification that appears on the display. In one example, activating an alarm comprises outputting an audible alarm, for example a beep, a siren, or other such sound from a sounder of the controller.

[0047]

[0045] In one example, the controller is arranged to output an indication corresponding to the effectiveness of the neuromuscular block as part of a feedback control system for administering a neuromuscular blocking agent or a neuromuscular block reversal reagent to a subject. In one example, the controller is arranged to output an indication corresponding to the effectiveness of the neuromuscular block as part of a feedback control system for administering a neuromuscular block reversal agent to a subject. That is, the controller is operatively coupled to a titration or other suitable delivery system for a neuromuscular blocking agent and / or a neuromuscular block reversal agent, and is arranged to control the delivery therefrom to a subject.

[0048]

[0046] In one example, the controller is arranged determine, based on the effectiveness of the neuromuscular block, the need to administer additional neuromuscular blocking agent to a subject. In one example, the controller is arranged to determine, based on the effectiveness of the neuromuscular block, the need to administer a neuromuscular block reversal agent to a subject.

[0049]

[0047] In one example, the controller is arranged to administer, based on the determined effectiveness of the neuromuscular block being too shallow a block, additional neuromuscular blocking agent to a subject. In one example, the controller is arranged to administer, based on the determined effectiveness of the neuromuscular block being too deep a block, a reduced amount of neuromuscular blocking agent thereafter, or to administer a neuromuscular block reversal agent.

[0050]

[0048] In one example, the controller is arranged to display a prompt to suggest such administering to be carried out by a human. For example, to display a prompt for a doctor, nurse, anaesthesiologist or other such individual responsible for monitoring paralysis of the subject.

[0051]

[0049] In one example, the controller is arranged to carry out such administering automatically as part of the feedback control system. In one example, the controller is arranged to carry out said administering automatically to keep the level of the neuromuscular block in a target range for the effectiveness of the neuromuscular block, as part of a feedback control system. In one example, the controller operates the feedback control system with an adaptive gain in the feedback loop. In one example the controller is arranged to vary the adaptive gain in the feedback loop according to the previous response of a subject to administration of a neuromuscular blocking agent. In one example, the controller operates the feedback loop with adaptive gain according to response trends predicted by Al or ML using data models. In this example, the data models may include stratified data based on, for example, age, sex and / or BML In these examples, the controller can vary the adaptive gain to determine the appropriate amount of neuromuscular blocking agent or neuromuscular block reversal agent to maintain the level of neuromuscular block in the target range more accurately.

[0052]

[0050] In one example, the electrode is for a muscle in the hand of a subject. In one example, the electrode is for a thenar muscle. In one example, the electrode is for one of: the opponens pollicis, the abductor pollicis brevis, and the flexor pollicis brevis. In one example, the electrode is for a superficial muscle. In one example, the electrode is for the abductor pollicis brevis. In one example, the peripheral nerve stimulator is for the median nerve. In one example, the peripheral nerve stimulator is for the recurrent branch of the median nerve.

[0053]

[0051] In one example, the electrode comprises a bipolar electrode. In one example, the electrode comprises a reference pole and a sense pole. In one example, the electrode comprises a plurality of sense poles, for measuring potential relative to a reference pole. In one example, the reference pole is referenced to a ground or earth potential.

[0054]

[0052] In one example, the electrode comprises a plurality of second poles that are spaced apart from one another, for example at equal spacing from one another. In one example, the second poles are arranged around the reference pole. In one example, the second poles are arranged in a plane. In one example, the second poles are arranged at a common distance from the reference pole, for example at the same offset from the reference pole. In one example, the second poles are arranged at a common distance from the end of the electrode. In one example, the reference pole is arranged centrally with respect to the second poles. In one example, the reference pole extends to a point, for example the extreme point, or end of the electrode. In one example, the reference pole comprises a tapered form, for example comprises a generally conical shape, for example a shape that is narrower toward the end of the electrode. In one example, the second pole(s) are arranged with the reference pole to form a tapered form. In one example the reference pole tapers at a first taper angle, and the second pole(s) taper at a second taper angle. In one example the second taper angle is greater than the first taper angle, i.e., the electrode gets wider more quickly in the region of the second pole(s), for example.

[0055]

[0053] In one example, the second pole(s) each comprise a separate electrical path for a sensed potential, with reference to the reference pole. In one example, the second pole(s) are formed from individually insulated wires. In one example, the second pole(s) are formed from wires that are wrapped around the reference pole, for example separately insulated wires. In one example, the second pole(s) are insulated, away from their ends, in parylene or another sufficiently insulating material. In one example, the wires are wrapped around the reference pole, spirally progressing away from the free end of the electrode. In one example, the second poles are interwound with one another. In one example, the electrode comprises an even number of second poles, for example 2 second poles. In one example, the electrode comprises a 2An electrodes, for example 4, 8, 16, 32, or 64, or more.

[0056]

[0054] In one example, the electrode comprises a sensing region at the end thereof. In one example, the sensing region is positionable at the neuromuscular junction(s).

[0057]

[0055] In one example, the reference pole is positionable at the neuromuscular junction(s).

[0058]

[0056] In one example, the end of the electrode is positionable at the neuromuscular junction(s).

[0059]

[0057] In one example, the sensing region comprises a three-dimensional region between the reference pole and the second pole(s).

[0060]

[0058] In one example the electrode comprises tungsten, for example the reference electrode comprises a tungsten needle. In one example, away from the end, the reference electrode is covered in insulating material, for example parylene.

[0061]

[0059] In one example, the electrode comprises a needle, for example a hypodermic needle, for example, a concentric needle electrode, for example, a cannula.

[0062]

[0060] In one example, the one or other of the reference pole and the electrode extends through the needle such that one of said poles is in an aperture at the end of the needle. That is to say, the pole is exposed on the external surface of the needle at the end of the needle.

[0063]

[0061] In one example, the needle is coated with a conductive substance that is ablated to form multiple helical paths which are then coated with an insulating coating. In one example, the insulating coating comprises parylene. In one example, the insulating coating is selectively ablated to form the second poles along the length of the electrode. BRIEF DESCRIPTION OF DRAWINGS

[0064]

[0062] For a better understanding of the invention, and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example, to the accompanying diagrammatic drawings in which:

[0065] Figure 1 shows a schematic plan view of an integrated electrode and peripheral nerve stimulator for a monitoring apparatus for determining the effectiveness of a neuromuscular block, in place on the hand of a human subject;

[0066] Figure 2 shows first and second enlarged views of portions of the electrode;

[0067] Figure 3 shows schematic side and plan view of the integrated electrode and peripheral nerve stimulator of Figure 1 ;

[0068] Figure 4 shows the integrated electrode and peripheral nerve stimulator of Figure 1 in a blister pack prior to use, and a monitoring apparatus for determining the effectiveness of a neuromuscular block in use on the hand of a human subject;

[0069] Figure 5 shows the integrated electrode and peripheral nerve stimulator of Figure 1 and a monitoring apparatus for determining the effectiveness of a neuromuscular block in use on the hand of a human subject

[0070] Figure 6 shows an example of an electrode for use in a monitoring apparatus for determining the effectiveness of a neuromuscular block;

[0071] Figure 7 shows another example of an electrode for use in a monitoring apparatus for determining the effectiveness of a neuromuscular block;

[0072] Figure 8 shows a further view of an example of an electrode for use in a monitoring apparatus for determining the effectiveness of a neuromuscular block;

[0073] Figure 9 shows a closeup view of an example of an electrode for use in a monitoring apparatus for determining the effectiveness of a neuromuscular block;

[0074] Figure 10 shows another view of an electrode for use in a monitoring apparatus for determining the effectiveness of a neuromuscular block;

[0075] Figure 11 shows further closeup view of examples of an electrode for use in a monitoring apparatus for determining the effectiveness of a neuromuscular block; and

[0076] Figure 12 shows a method of using the integrated electrode and peripheral nerve stimulator of Figure 1 for determining the effectiveness of a neuromuscular block.

[0077] DESCRIPTION OF EXAMPLE EMBODIMENTS

[0078]

[0063] Referring to Figure 1 an integrated electrode 102 and peripheral nerve stimulator 103 are shown schematically, in place on the hand 101 of a human subject. The electrode 102 comprises a multipolar needle electrode, which is inserted in the thenar muscles of the hand 101 . The peripheral nerve stimulator 103 is arranged to overlie the median nerve of the subject.

[0079]

[0064] The integrated electrode 102 and peripheral nerve stimulator 103 are used in a method of neuromuscular monitoring for determining the effectiveness of a neuromuscular block. The method comprises inserting an electrode 102 into a muscle of a mammalian subject that is supplied with a singular branch of innervation. The electrode 102 is positioned to extend to an innervation end point of the muscle. With this arrangement, the inventors have determined a subthreshold potential at a neuromuscular junction of the muscle that can be used to monitor the effectiveness of neuromuscular block. That is, rather than neuromuscular monitoring that requires activation of a muscle to determine the effectiveness of a neuromuscular block, a relatively sensitive determination can be made by considering the potential at the neuromuscular junction when this is the singular innervation route for the muscle.

[0080]

[0065] The existence of a monitorable sub-threshold potential at a neuromuscular junction(s) of the muscle results from provision of a stimulus to the relevant nerve branch. In the example of Figure 1 , the peripheral nerve stimulator 103 comprises a pair of stimulating electrodes. More specifically, as shown in Figure 2, the pair of stimulating electrodes comprise a positive skin contacting electrode and a negative skin contacting electrode that are each supplied by paths 204, 205 and extend to a positive 207 and a negative 208 terminal 21 1 .

[0081]

[0066] In the example the specific muscle being monitored is the abductor pollicis brevis, which is innervated by the recurrent branch of the median nerve. In human mammalian subjects, this muscle and nerve are readily accessible. A sub-threshold potential at the neuromuscular junction means the potential below that required potential for a recruitment of a cascade of muscle fibres. If a neuromuscular block is in place, as a result of administering a neuromuscular blocking agent, innervation signals from the nerve are not passed to the muscle fibres. However, even in this scenario the inventors have determined that a measurable change in potential may exist at the neuromuscular junction. For example, in typical human subjects, in the hand example above, a sub-threshold potential in the range of -75mV to -50mV may be produced when a clinically acceptable level of neuromuscular block is in place and the recurrent branch of the median nerve is stimulated. By monitoring this sub-threshold potential, over the course of the neuromuscular block, more, or less neuromuscular blocking agent, or indeed a reversal agent may be administered as required.

[0082]

[0067] Figure 2 shows the needle electrode 201 in closeup, where the ends of the sensing wires 202 create a three-dimensional sensing area 203. The electrode 201 and positive 204 and negative 205 stimulus paths run along a flexible foam adhesive backing 206 to the positive 207, and negative 208 electrode terminations 211 as mentioned. The electrode 201 is mounted to a printed circuit board 209 that integrates with a needle electrode body 210. In Figure 4 these components are shown in a blister pack 301 , together forming a disposable electrode assembly 302, intended to be supplied as a sterile single-use assembly that comprises all the subjectcontacting elements in the monitoring apparatus.

[0083]

[0068] Figure 5 shows a system overview in which the electrode assembly 302 is connected via an umbilical cable 303 to a controller 304 that includes a display 305 providing a graphical user interface. The umbilical cable 303 delivers stimulus pulses to the electrode assembly 302, while simultaneously monitoring the response signals from the electrode 201 . For the apparatus to function automatically, a secondary control cable 306 is connected to an infusion pump 307 in a delivery system for controlled doses of a pharmacological agent 308 via an intravenous line 309. The pharmacological agent 308 suitably comprises a neuromuscular blocking agent.

[0084]

[0069] Figures 6 and 7 show another example of a needle electrode 401 , that is formed from a solid or hollow tube 402 is coated with a conductive substance 404 that is then ablated to form multiple helical paths 403. These paths are then coated with a non-conductive coating 405 such as parylene. The non-conductive coating 405 is selectively ablated to form sensing poles along the length 406 of the needle electrode 401 .

[0085]

[0070] Still further suitable electrode configurations are shown in Figures 8, 9, 10 and 11 . They are provided to explain the construction of electrodes like that shown in Figure 2. Figures 8 and 10 show the a solid inner electrode 502 mounted to a printed circuit board 501 . Figures 9 and 1 1 show multiple insulated sensing wires 503 wrapped around the solid core 502 and bonded in place. The conducting wires 503 suitably comprise tungsten for flexibility and strength, and have a diameter of 12.5pm. UV (ultraviolet) curable glue is used to bond the conducting wires 503 in place. The bonded assembly is then ground into a desired tapering shape 504 exposing the ends central tip as the reference pole and the ends of the conducting wires as the second pole(s).

[0086]

[0071] Figure 12 shows a method of using an integrated electrode 102 and peripheral nerve stimulator 103 for determining the effectiveness of a neuromuscular block. The first step 601 of the method comprises inserting an electrode 102 into a muscle of a mammalian subject, wherein the muscle has a singular branch of innervation. The second step 602 comprises stimulating the nerve that provides the singular branch of innervation to the muscle, for example proximal to the muscle. The third step 603 comprises using the electrode 102 to monitor the sub-threshold potential at the neuromuscular junction in response to the stimulus. The method may contain a fourth step 604 that comprises processing the signal received from the electrode 102 to produce an indication of the effectiveness of the neuromuscular block, and a fifth step 605 of outputting an indication of the effectiveness of the neuromuscular block. The method may further comprise a sixth step of determining the amount of pharmacological agent 308, for example, neuromuscular blocking agent or neuromuscular block reversal agent, to be administered to the patient based on the determined effectiveness of the neuromuscular block. The method may further comprise a seventh step of administering the determined amount of pharmacological agent 308 to the patient. To continue monitoring the effect of neuromuscular block on the patient this process is repeated from the second step 602. Once monitoring of the effect of neuromuscular block on the patient has been stopped, the electrode 102 and peripheral nerve stimulator 103 are removed from the patient and the single-use component(s) are disposed of.

[0087]

[0072] In a related approach, there is provided a computer-readable storage medium comprising instructions which, when executed by a processor, causes the processor to carry out any of the methods described herein.

[0088]

[0073] As will be appreciated by one skilled in the art, the present techniques may be embodied as a system, method or computer program product. Accordingly, present techniques may take the form of an entirely hardware embodiment, an entirely software embodiment, or an embodiment combining software and hardware aspects.

[0089]

[0074] Furthermore, the present techniques may take the form of a computer program product embodied in a computer readable medium having computer readable program code embodied thereon. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable medium may be, for example, but is not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing.

[0090]

[0075] Computer program code for carrying out operations of the present techniques may be written in any combination of one or more programming languages, including object oriented programming languages and conventional procedural programming languages. Code components may be embodied as procedures, methods or the like, and may comprise subcomponents which may take the form of instructions or sequences of instructions at any of the levels of abstraction, from the direct machine instructions of a native instruction set to high-level compiled or interpreted language constructs.

[0091]

[0076] Embodiments of the present techniques also provide a non-transitory data carrier carrying code which, when implemented on a processor, causes the processor to carry out any of the methods described herein.

[0092]

[0077] The techniques further provide processor control code to implement the above-described methods, for example on a general-purpose computer system or on a digital signal processor (DSP). The techniques also provide a carrier carrying processor control code to, when running, implement any of the above methods, in particular on a non-transitory data carrier. The code may be provided on a carrier such as a disk, a microprocessor, CD- or DVD-ROM, programmed memory such as non-volatile memory (e.g. Flash) or read-only memory (firmware), or on a data carrier such as an optical or electrical signal carrier. Code (and / or data) to implement embodiments of the techniques described herein may comprise source, object or executable code in a conventional programming language (interpreted or compiled) such as Python, C, or assembly code, code for setting up or controlling an ASIC (Application Specific Integrated Circuit) or FPGA (Field Programmable Gate Array), or code for a hardware description language such as Verilog (RTM) or VHDL (Very high speed integrated circuit Hardware Description Language). As the skilled person will appreciate, such code and / or data may be distributed between a plurality of coupled components in communication with one another. The techniques may comprise a controller which includes a microprocessor, working memory and program memory coupled to one or more of the components of the system.

[0093]

[0078] It will also be clear to one of skill in the art that all or part of a logical method according to embodiments of the present techniques may suitably be embodied in a logic apparatus comprising logic elements to perform the steps of the above-described methods, and that such logic elements may comprise components such as logic gates in, for example a programmable logic array or application-specific integrated circuit. Such a logic arrangement may further be embodied in enabling elements for temporarily or permanently establishing logic structures in such an array or circuit using, for example, a virtual hardware descriptor language, which may be stored and transmitted using fixed or transmittable carrier media.

[0094]

[0079] In an embodiment, the present techniques may be realised in the form of a data carrier having functional data thereon, said functional data comprising functional computer data structures to, when loaded into a computer system or network and operated upon thereby, enable said computer system to perform all the steps of the above-described method.

[0095]

[0080] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0096]

[0081] All the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive.

[0097]

[0082] Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent, or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0098]

[0083] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Claims

CLAIMS1. A method of neuromuscular monitoring for determining the effectiveness of a neuromuscular block, the method comprising: inserting an electrode into a muscle of a mammalian subject, wherein the muscle has a singular branch of innervation, and the electrode extends to an innervation end point, characterised by monitoring a sub-threshold potential at a neuromuscular junction of the muscle.

2. The method of claim 1 , comprising providing proximal nerve stimulus for the nerve that provides the singular branch of innervation, and using the electrode to monitor the sub-threshold potential at a neuromuscular junction of the muscle in response to the stimulus.

3. The method of any preceding claim, comprising stimulating the nerve with a series of pulses.

4. The method of any preceding claim, wherein the method is commenced before administration of a neuromuscular block, and continues while the neuromuscular block is in place until the effect of the neuromuscular block is ended.

5. The method of any preceding claim, comprising processing the signal received from the electrode to produce an indication of the effectiveness of a neuromuscular block, and outputting an indication corresponding to the effectiveness of the neuromuscular block, such as outputting an indication of whether the effectiveness of the neuromuscular block is increasing or decreasing.

6. The method of any preceding claim, comprising determining a target range for the effectiveness of the neuromuscular block, and activating an alarm if the effectiveness of the neuromuscular block is not within the target range.

7. The method of any preceding claim, comprising determining, based on the effectiveness of the neuromuscular block, the need to administer additional neuromuscular blocking agent to a subject; or the need to administer a neuromuscular block reversal agent to a subject to maintain the effectiveness of the neuromuscular block within a target range.

8. The method of claim 7, comprising administering, based on the determined effectiveness of the neuromuscular block being too shallow a block, additional neuromuscular blocking agent to a subject; or administering, based on the determined effectiveness of the neuromuscular block being too deep a block, a reduced amount of neuromuscular blocking agent thereafter, or administering a neuromuscular block reversal agent.

9. The method of claim 8, comprising performing the administering automatically as part of the feedback control system.

10. The method of claim 9, performing the administering automatically is to keep the level of the neuromuscular block in a target range for the effectiveness of the neuromuscular block, as part of a feedback control system that comprises an adaptive gain in the feedback loop.11 . The method of claim 10, wherein the adaptive gain is determined according to the previous response of the subject to administration of a neuromuscular blocking agent.

12. The method of any preceding claim, wherein the muscle being monitored is the abductor pollicis brevis as innervated by the recurrent branch of the median nerve, with the sub-threshold potential is the threshold at the neuromuscular junction between the resting potential and the threshold value at which recruitment cascade of muscle fibres occurs.

13. A neuromuscular monitoring apparatus for determining the effectiveness of a neuromuscular block, the apparatus comprising: an electrode for inserting into a muscle of a mammalian subject, the muscle having a singular branch of innervation, and characterised by a controller to monitor a sub-threshold potential at the neuromuscular junction of the muscle.

14. The apparatus of claim 13, comprising a peripheral nerve stimulator, wherein the electrode and peripheral nerve stimulator comprise an integrated, single use, component.

15. The apparatus of claim 13 or 14, wherein the electrode comprises a reference pole and a plurality of sense poles for measuring potential relative to a reference pole, the sense poles being spaced apart from one another to provide a sensing in a three-dimensional sensing region positionable at the neuromuscular junction.

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