HK1237236B - A device and means of assessing neuromuscular junction status with higher fidelity - Google Patents

Description

Device and method for assessing neuromuscular junction status with higher fidelity

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 62/853,193, filed November 26, 2014, which is incorporated herein by reference in its entirety.

Technical Field

Embodiments of the present technology generally relate to the field of clinical neurophysiology. More specifically, they relate to devices and methods for assessing the neuromuscular junction and the level of pharmacological blockade during anesthesia. Such devices can be used to determine the degree of muscle relaxation during and at the end of surgery to ensure adequate surgical intervention and recovery from anesthesia.

Background Art

Quantitative measurement of the depth of neuromuscular blockade during surgery and at other times is widely recognized as important, particularly to prevent residual paralysis in postoperative patients. Current techniques require the anesthesiologist to use equipment that employs mechanical myography, accelerometer myography, myophonography, and/or electromyography recording methods.

All measurements of neuromuscular blockade employed by these devices rely on stimulating a nerve containing motor fibers and recording activity from the corresponding innervated muscle to quantify the response. Typically, the integrated compound motor potential or tension generated by the muscle in response to stimulation of the ulnar nerve is recorded. A variation of the latter, developed by Viby-Mogensen, records the acceleration of the rate of tension development rather than the tension itself, as the two are directly proportional.

One of two strategies is typically used to determine the relative degree of muscle block or relaxation over time: maximal contraction measurements with single or multiple stimulations to obtain the maximal muscle response that can be followed over time, and fatigue or senescence of the muscle response after repeated stimulation or high-frequency auxiliary stimulation to induce tetany (post-tetanic techniques). While all neuromuscular blocking compounds necessarily produce relaxation, not all products produce senescence. Most, if not all, commercially available agents produce senescence.

Common techniques for determining neuromuscular blockade use stimulation at a standard frequency to induce tetany and record the muscle response. A popular method for measuring the degree of neuromuscular blockade is the train-of-four (TOF) method, which features four stimuli delivered at 2 Hz and measures the presence or absence of a response to the stimulus, as well as the amplitude of the muscle response—or the ratio of the area under the curve—of the fourth response compared to the first. Other techniques involving the application of tetanic stimulation are less well-known to most anesthesiologists and are therefore rarely or inadequately used.

Summary of the Invention

Generally, embodiments disclosed herein provide an automated device and system that follows a predetermined stimulation protocol for intermittently or continuously monitoring the level of neuromuscular blockade throughout a procedure by automatically adjusting the frequency or number of stimulations delivered, based on the current degree of blockade, to improve the reproducibility and fidelity of the measurements. The device also uses novel technology to more accurately reflect the expected physiological intensity.

Applicants have identified a need for improved measurement of muscle and neuromuscular junction strength and fatigue in patients receiving neuromuscular blockade, and for displaying the data in a clear and easily understood manner. The embodiments described herein are based, at least in part, on Applicants' discovery of a need for simple, easy-to-use devices and methods that automatically adjust the level of neuromuscular blockade and improve the reproducibility and apparent quality of strength and fatigue measurements. These embodiments disclosed herein are particularly useful within the bounds of current technologies, such as time-of-flight (TOF), which are less accurate and prone to error.

Quantitative measurements, commonly used to measure the degree of block, have been found to be superior to anesthesiologists' qualitative assessments of blockade. However, quantitative measurements achieved with existing equipment and techniques may not be sufficient to determine adequate reversal of neuromuscular blockade or be clinically beneficial to the user. Therefore, embodiments of the present technology provide systems and methods for quantitatively measuring adequate reversal of neuromuscular junction blockade to ensure that the patient has adequate breathing capacity and to ensure patient safety with increased resolution and reproducibility. While current recommendations suggest that a reduction of only 10% from the fourth to the first response in a train-of-four (TOF) measurement is safe (Lien, 2014), even in normal muscle, responses to low-frequency stimulation can vary by as much as 5–8% (see, e.g., Kimura, 2013). Furthermore, motion artifacts in the measured responses, interference from electrocautery, lower-quality amplifiers, and lack of adequate filtering may contribute to further variability. Warming the patient after extubation may reduce the efficiency of the neuromuscular junction and shift the patient from a safe state to a potentially unsafe state. These factors make determining a safety margin difficult.

Embodiments described herein generally relate to devices and methods for measuring the degree of neuromuscular blockade in a patient, particularly within a safe range of blockade. Various embodiments relate to devices, systems, and methods for obtaining and processing recorded signals in a manner that reduces or eliminates interference from electrosurgical devices while preserving target biosignals.

In one aspect, disclosed herein is a device for more accurately assessing the degree of neuromuscular blockade that automatically applies stimulation at varying frequencies and amounts and measures the muscle response. In another aspect, disclosed herein is a method for more accurately assessing the degree of neuromuscular blockade that automatically applies stimulation at varying frequencies and amounts and measures the muscle response.

In another aspect, disclosed herein is an apparatus comprising at least one stimulating electrode, at least one recording electrode, a pulse generator for providing stimulation to a nerve via the stimulating electrode, and a computing device comprising a processor having instructions stored thereon. When executed by the computing device, the instructions cause the computing device to apply stimulation to the nerve via the stimulating electrode according to a stimulation protocol with varying frequencies and quantities, measure an electrical response of a muscle, and assess a degree of neuromuscular blockade based on changes in the electrical response of the muscle.

In another aspect, disclosed herein is a method for assessing the degree of neuromuscular blockade, comprising stimulating a nerve with a stimulation electrode according to a stimulation protocol with varying frequencies and numbers of stimulations, measuring the electrical response of a muscle, and assessing the degree of neuromuscular blockade based on changes in the electrical response of the muscle. In some aspects, the assessment is more accurate than standard train-of-four stimulation analysis. In some aspects, the method further comprises automatically adjusting the stimulation protocol based on the current degree of blockade to improve the reproducibility and fidelity of the measurement.

In another aspect, disclosed herein is a system comprising at least one stimulating electrode, at least one recording electrode, a pulse generator for providing stimulation to a nerve via the stimulating electrode, and a computing device comprising a processor having instructions stored thereon. When executed by the computing device, the instructions cause the computing device to apply stimulation to the nerve via the stimulating electrode according to a stimulation protocol, wherein the stimulation protocol provides a plurality of stimulation sequences having different pulse frequencies within the stimulation sequences, different frequencies within the stimulation sequences, different numbers of pulses within the stimulation sequences, or all of the foregoing; measure an electrical response of a muscle via the recording electrode; and assess a degree of neuromuscular blockade based on changes in the electrical response of the muscle during a stimulation sequence.

In some embodiments, assessing the degree of neuromuscular blockade comprises determining a ratio between the electrical response of a muscle from a first pulse in a stimulation sequence and the electrical response of the muscle from a last pulse in the stimulation sequence. In some embodiments, the number of pulses in a stimulation sequence is between 4 and 20 pulses. In some embodiments, the number of pulses increases with each subsequent stimulation sequence in the stimulation protocol. In some embodiments, the frequency of pulses in a stimulation sequence is between 2 Hz and 10 Hz. In some embodiments, the frequency of pulses increases with each subsequent stimulation sequence in the stimulation protocol.

In some embodiments, the stimulation protocol includes a first stimulation sequence of four pulses at a first frequency, a second stimulation sequence of four pulses at a second frequency higher than the first frequency, and a third stimulation sequence of four pulses at a third frequency higher than the second frequency. In some embodiments, the stimulation protocol also includes a fourth stimulation sequence of more than four pulses.

In some embodiments, the processor further comprises instructions that, when executed by the computing device, cause the computing device to operate automatically without user input. In some embodiments, the computing device automatically determines whether the stimulation protocol requires adjustment and adjusts the stimulation protocol. In some embodiments, the computing device determines whether the stimulation protocol requires adjustment at predetermined intervals based on electrical response readings above or below a threshold, in response to other physical parameters of the patient and/or consistent with program timing.

In some embodiments, the nerve is a peripheral nerve. In some embodiments, the peripheral nerve is at least one of the nerves in the group consisting of an ulnar nerve, a median nerve, a peroneal nerve, and a posterior tibial nerve. In some embodiments, the stimulation electrode is configured to be positioned on the patient's wrist or ankle.

In some embodiments, the system further comprises a display unit for displaying information about the patient. In some embodiments, the information is information related to the degree of neuromuscular blockade. In some embodiments, the system further comprises a signal amplifier to reduce factors that confound the electrical response signal, wherein the signal amplifier includes one or more of a CMRR greater than 96 dB, stimulation artifact filtering, and electrocautery signal detection.

On the other hand, the present invention discloses a method for assessing the degree of neuromuscular blockade, comprising: applying stimulation to a nerve using a pulse generator through a stimulation electrode according to a stimulation scheme, wherein the stimulation scheme provides multiple stimulation sequences, and the multiple stimulation sequences have different pulse frequencies in the stimulation sequences, frequencies in the stimulation sequences, numbers of pulses in the stimulation sequences, or all of the above; measuring the electrical response of a muscle; and assessing the degree of neuromuscular blockade based on changes in the electrical response of the muscle during a stimulation sequence.

In some embodiments, assessing the degree of neuromuscular blockade comprises determining a ratio between the electrical response of the muscle from a first pulse in a stimulation sequence and the electrical response of the muscle from a last pulse in the stimulation sequence.

In some embodiments, the nerve is a peripheral nerve. In some embodiments, the peripheral nerve is at least one of the group consisting of an ulnar nerve, a median nerve, a peroneal nerve, and a posterior tibial nerve. In some embodiments, the stimulation electrode is positioned on the patient's wrist or ankle.

In some embodiments, the stimulation protocol includes a first stimulation sequence of four pulses at a first frequency, a second stimulation sequence of four pulses at a second frequency higher than the first frequency, and a third stimulation sequence of four pulses at a third frequency higher than the second frequency. In some embodiments, the stimulation protocol also includes a fourth stimulation sequence of more than four pulses.

In some embodiments, information related to the degree of neuromuscular blockade is displayed on a display unit. In some embodiments, the method further comprises determining whether the stimulation regimen requires adjustment based on the assessment of the degree of neuromuscular blockade, and adjusting the stimulation regimen. In some embodiments, the computing device determines whether the stimulation regimen requires adjustment at predetermined intervals based on electrical response readings above or below a threshold, in response to other physical parameters of the patient and/or consistent with program timing.

In some embodiments, the method further comprises providing a signal amplifier to reduce factors that confound the electrical response signal, wherein the signal amplifier comprises one or more of a CMRR >96 dB, stimulation artifact filtering, and detection of electrocautery signals.

In another aspect, disclosed herein is a device for assessing the degree of neuromuscular blockade, the device being configured to provide a first set of electrical stimuli to a nerve, measure a muscle response to the stimuli, and automatically adjust the stimuli by changing the pulse frequency in a second set of stimuli, the number of pulses in the second set of stimuli, or both.

In another aspect, disclosed herein is a computerized method for assessing the degree of neuromuscular blockade, comprising delivering a first set of electrical stimuli to a nerve, measuring a muscle response to the stimuli, and automatically adjusting the stimuli by varying the pulse frequency in a second set of stimuli, the number of pulses in the second set of stimuli, or both.

BRIEF DESCRIPTION OF THE DRAWINGS

The above features and other features, aspects and advantages of the present technology will now be described in conjunction with various embodiments of the present invention with reference to the accompanying drawings. However, the illustrated embodiments are merely examples and are not intended to limit the present invention.

FIG1 depicts a functional block diagram of one embodiment of a system for monitoring and measuring strength and fatigue of muscles and neuromuscular junctions.

FIG2 depicts a functional block diagram of one embodiment of a computer system that may be used in conjunction with, connect with, and/or replace the systems and components described herein.

3 is a series of graphs depicting the amplitude ratio between the first stimulus in a series and the last stimulus in a series for different frequencies and numbers.

4 is a series of graphs depicting the amplitude ratio between the first stimulus in a series and the last stimulus in a series for different frequencies.

5a-5b provide a comparison of determining the onset of a muscle response when the stimulation artifact has not been cleared (5a) and when the stimulation artifact has been removed by the adaptive filter (5b).

DETAILED DESCRIPTION

In the following detailed description, reference is made to the accompanying drawings which form a part of the present disclosure. The embodiments described in the drawings and the specification are intended to be illustrative and not limiting. As used herein, the term 'exemplary' means 'serving as an example or illustration' and should not necessarily be construed as preferred or advantageous over other embodiments. Other embodiments may be utilized and variations may be made without departing from the spirit or scope of the subject matter presented herein. As described and illustrated herein, aspects of the present disclosure may be arranged, combined and designed in a variety of different configurations, all of which are expressly contemplated and form a part of this disclosure.

definition

Unless otherwise defined, the meaning of each technical term or scientific term used herein is the same as that commonly understood by those of ordinary skill in the art to which this disclosure belongs. In accordance with the claims below and the disclosure provided herein, unless otherwise explicitly stated, the following terms are defined to have the following meanings.

When the term "about" or "approximately" is used before a numerical designation or numerical range (eg, pressure or size), it indicates an approximation that may vary by (+) or (-) 5%, 1%, or 0.1%.

As used in the specification and claims, the singular forms "a," "an," and "the" include both the singular and the plural, unless the context clearly dictates otherwise. For example, the term "an evoked potential" may include, and is contemplated to include, a plurality of evoked potentials. The claims and specification may sometimes include terms such as "a plurality," "one or more," or "at least one"; however, the absence of such terms is not to be construed, and should not be construed, as meaning that the plural form cannot be constructed with respect to a particular embodiment.

With respect to any plural and/or singular terms used herein, those skilled in the art may translate from the plural to the singular and/or from the singular to the plural as appropriate to the context and/or application. For clarity, various singular/plural permutations may be explicitly set forth herein.

As used herein, the terms "comprising" or "comprises" are intended to mean that the apparatus, systems, and methods include the recited elements and may additionally include any additional elements. For purposes of this disclosure, "consisting essentially of" will mean that the apparatus, systems, and methods include the recited elements and exclude other elements that are essential to the combination. Thus, as defined herein, an apparatus or method consisting essentially of the elements will not exclude other materials or steps that do not materially affect the basic and novel characteristic(s) of the invention. "Consisting of" will mean that the apparatus, systems, and methods include the recited elements and exclude any elements or steps that are beyond those that are minor or insignificant. Embodiments defined by each of these transition terms are within the scope of this disclosure.

System Overview

FIG1 depicts a block diagram of a system for stimulating nerves and measuring muscle and neuromuscular junction strength and fatigue in a patient receiving neuromuscular blocking agents, according to one embodiment of the present disclosure. In the depicted embodiment, a system 100 that can be coupled to a patient 101 includes, but is not limited to, one or more recording electrodes 102, one or more stimulation electrodes 103, a paralysis assessment device 104, and a display unit 106.

In some embodiments of the system 100, the stimulation electrodes 103 are configured to be placed on or near the arm or leg of the patient 101, on peripheral nerve structures such as the ulnar nerve, median nerve, peroneal nerve, and/or posterior tibial nerve. In some embodiments, the stimulation electrodes 103 are configured to be placed on the skin of the patient's wrist and ankle, such that the electrodes are located on or near the ulnar nerve and the posterior tibial nerve. This configuration allows for comprehensive patient monitoring of peripheral nerves (i.e., monitoring nerves in all limbs). In other embodiments, the system 100 can be used only for upper limb monitoring; in such embodiments, the stimulation electrodes 103 can be configured to be placed on the skin of the patient's wrist, for example, only on or near the ulnar nerve. Some embodiments of the recording electrodes 102 are configured to be placed on the wrist or ankle, or other locations where the response of muscles and neuromuscular junctions to stimulation from the stimulation electrodes 103 can be measured.

In various embodiments, the paralysis assessment device 104 is electrically coupled to the recording electrodes 102 and the stimulation electrodes 103 via a plurality of cables, or the electrodes may be wirelessly coupled thereto. Various embodiments of the paralysis assessment device 104 form part of, are coupled to, and/or include a computing device, such as, for example, computing device 200 described in further detail below with reference to FIG. The paralysis assessment device 104 may include or be coupled to a pulse generator to provide stimulation via the stimulation electrodes 103. In various embodiments, the paralysis assessment device 104 is also electrically, electronically, and/or mechanically coupled to the display unit 160 via a link 150. In some embodiments, the link 150 is internal wiring or an external cable. In some embodiments, the link 150 is a wireless communication link. For example, in some embodiments, the paralysis assessment device 104 is wirelessly coupled to the display unit 160 via Bluetooth® or other radio frequency signals, or via near-field communication or cellular signals.

The display unit 106 can display various information on a graphical user interface (GUI), such as, but not limited to, patient biometric information, recommended electrode positions, stimulation parameters, stimulated and recorded areas, baseline and current signal traces, historical trends in the signal, relevant changes in the signal, locations of signal changes, recorded signal quality, electrode positions, alerts due to significant changes in the signal, and recommended movements to mitigate adverse signal changes. Furthermore, the display unit 106 can include an input user interface comprising, for example, a touch screen, buttons, and/or control inputs. According to some embodiments, the input user interface allows an operator to set up an initial monitoring design and interact with the display unit 106 during monitoring to add additional information, view information in different formats, or respond to alerts. In some embodiments, the display unit 106 can allow an anesthesiologist or other medical personnel, for example, to override signal changes when the signal change is related to or attributed to a dose change of the anesthetic agent or some other event unrelated to localization effects or neuromuscular blockade.

Various embodiments of system 100 also include software that facilitates automation of system 100. This software may be stored in memory and executed by a processor located within system 100. In various embodiments, the memory and processor are components of a computer, and in at least some such embodiments, the paralysis assessment device 104 comprises a portion of, is coupled to, and/or includes a computer via a wired or wireless connection. Additionally, in some embodiments, system 100 includes one or more user interfaces to receive input from a user and provide output to the user. Such user interfaces may comprise a portion of the computer or may be in electrical or wireless communication with the computer. The user interfaces in some embodiments further facilitate automation of system 100.

The computing device 200 includes a processor and a memory and stores programmed instructions. When the processor executes the instructions, it causes the device to: (1) deliver stimulation (in the form of current or voltage) to the stimulation electrodes, and (2) record the detection signals picked up at the recording electrodes. FIG2 depicts a block diagram of an exemplary embodiment of a computer system that may form part of any of the systems described herein. Specifically, FIG2 shows an example computer 200 that may run an operating system such as available Microsoft® WINDOWS® NT/98/2000/XP/CE/7/VISTA/RT/8, etc., from Microsoft® Corporation of Redmond, Washington, USA, SOLARIS® from SUN® Microsystems of Santa Clara, California, USA, OS/2 from IBM® Corporation of Armonk, New York, USA, iOS or Mac/OS from Apple® Corporation of Cupertino, California, USA, or various versions of UNIX® (a trademark of The Open Group of San Francisco, California, USA), including, for example, LINUX®, HPUX®, IBM AIX®, and SCO/UNIX®, or Android® from Google® Corporation of Mountain View, California, USA. These operating systems are provided for example only; embodiments of the systems described herein may be implemented on any suitable computer system running any suitable operating system.

For example, other potential components of system 100, such as computing devices, communication devices, personal computers (PCs), laptop computers, tablet computers, mobile devices, client workstations, thin clients, thick clients, proxy servers, network communication servers, remote access devices, client computers, server computers, routers, network servers, data, media, audio, video, telephony servers, or streaming servers, etc., may also be implemented using computers such as the one shown in FIG. 2 .

Computer system 200 may include one or more processors, such as processor(s) 204. Processor(s) 204 may be connected to a communication infrastructure 206 (e.g., a communication bus, a cross-over bar, or a network). Various software embodiments may be described with respect to this exemplary computer system. After reading this description, it will become apparent to those skilled in the relevant art(s) how to implement the described methods using other computer systems and/or architectures.

Computer system 200 may include a display interface 202 that forwards graphics, text, and other data from communication infrastructure 206 for display on a display unit 230 .

For example, computer system 200 may also include, but is not limited to, a main memory 208, a random access memory (RAM), and a secondary memory 210. For example, secondary memory 210 may include, but is not limited to, a hard disk drive 212 and/or a removable storage drive 214, representing a floppy disk drive, a magnetic tape drive, an optical disk drive, a magneto-optical disk drive, a compact disc drive (CD-ROM), a digital versatile disc (DVD), a write-once-read-many (WORM) device, a flash memory device, and the like. Removable storage drive 214 may read from and/or write to a removable storage unit 218 in a well-known manner. For example, removable storage unit 218 may represent a floppy disk, a magnetic tape drive, an optical disk, a magneto-optical disk, a compact disc, a flash memory device, and the like, which can be read from and written to by removable storage drive 214. As will be appreciated, removable storage unit 218 may include a computer-usable storage medium having computer software and/or data stored therein.

In alternative exemplary embodiments, the second memory 210 may include other similar devices for allowing computer programs or other instructions to be loaded into the computer system 200. For example, such devices may include a removable storage unit 222 and an interface 220. Such examples may include a program cartridge and cartridge interface (such as, but not limited to, those found in some video game devices), a removable memory chip (such as, for example, but not limited to, an erasable programmable read-only memory (EPROM) or a programmable read-only memory (PROM) and an associated slot), and other removable storage units 222 and interfaces 220 that may allow software and data to be transferred from the removable storage unit 222 to the computer system 200.

For example, computer 200 may also include input devices 216, such as a mouse or other pointing device such as a digitizer, a touch screen, a microphone, a keyboard, and/or other data input devices. For example, computer 200 may also include output devices 240, such as display 230 and/or display interface 202. Computer 200 may include input/output (I/O) devices, such as communication interface 224, cables 228, and/or communication paths 226. These devices may include, but are not limited to, network interface cards and modems. Communication interface 224 may allow software and data to be transferred between computer system 200 and external devices. Examples of communication interface 224 include modems, network interfaces (such as Ethernet cards), communication ports, Personal Computer Memory Card International Association (PCMCIA) slots and cards, and the like. Software and data transferred via communication interface 224 may be in the form of signals 228, which may be electronic, electromagnetic, optical, or other signals capable of being received by communication interface 224. For example, these signals 228 may be provided to communication interface 224 via communication paths 226 (such as channels). For example, the channel 226 may carry a signal 228 (eg, a propagated signal) and may be implemented using wire or cable, fiber optics, a phone line, a cellular link, a radio frequency (RF) link, other communication channels, and the like.

In various embodiments described herein, the wired network may include any of a variety of well-known tools for coupling voice communication devices and data communication devices together. For example, in various embodiments described herein, the wireless network type may include, but is not limited to, code division multiple access (CDMA), wireless spread spectrum, orthogonal frequency division multiplexing (OFDM), 1G wireless, 2G wireless, 3G wireless, or 4G wireless, Bluetooth, Infrared Data Association (IrDA), Shared Wireless Access Protocol (SWAP), "Wireless Fidelity (Wi-Fi)", WiMAX, and other IEEE Standard 802.11 compliant wireless local area networks (LANs), IEEE Standard 802.16 compliant wide area networks (WANs), and ultra-wideband (UWB) networks.

Some embodiments may include or otherwise refer to a WLAN. Examples of WLANs may include the Shared Wireless Access Protocol (SWAP) developed by Home Radio Frequency (HomeRF), and Wireless Fidelity (Wi-Fi), a derivative of IEEE 802.11 promoted by the Wireless Ethernet Compatibility Alliance (WECA). The IEEE 802.11 wireless LAN standard refers to various technologies that conform to one or more of various wireless LAN standards. An IEEE 802.11-compliant wireless LAN may conform to any one or more of the various IEEE 802.11 wireless LAN standards. For example, the IEEE 802.11 wireless LAN standards include wireless LANs compatible with IEEE Standards 802.11a, 802.11b, 802.11d, 802.11g, or 802.11n, such as, but not limited to, IEEE Standards 802.11a, 802.11b, 802.11d, 802.11g, and 802.11n (e.g., including but not limited to IEEE 802.11g-2003, etc.).

Some embodiments described herein are directed to apparatuses and/or devices for performing the operations described herein. Such apparatuses may be specially constructed for the intended purpose, or they may comprise general-purpose devices selectively activated or reconfigured by a program stored on the device to perform a specific purpose.

Other embodiments described herein are directed to instructions stored on a machine-readable medium that can be read and executed by a computing platform to perform the operations described herein. A machine-readable medium may include any mechanism for storing or transmitting information in a form readable by a machine (e.g., a computer). For example, exemplary machine-readable storage media may include read-only memory (ROM), random-access memory (RAM), magnetic disk storage media, optical storage media, magneto-optical storage media, flash memory devices, and other exemplary storage devices capable of storing electrical, optical, acoustic, or other forms of propagated signals (e.g., carrier waves, infrared signals, digital signals, etc.), among others. A computer program (also referred to as computer control logic) may include an object-oriented computer program and may be stored in main memory 208 and/or secondary memory 210 and/or removable storage unit 214, also referred to as a computer program product. When executed, such a computer program may enable computer system 200 to perform the features of the present invention as discussed herein. Specifically, according to exemplary embodiments, when executed, such a computer program may enable processor 204 or processors 204 to provide methods for controlling and/or managing the operation of the EPDD. Thus, such a computer program may represent a controller of computer system 200.

Another exemplary embodiment is directed to a computer program product comprising a computer-readable medium having control logic (computer software) stored therein. When executed by processor 204, this control logic can cause processor 204 to perform the functions described herein. In other embodiments, the various functions described herein may be implemented primarily in hardware using, but not limited to, hardware components such as application-specific integrated circuits (ASICs) or one or more state machines. Implementing a hardware state machine to perform the functions described herein will be readily apparent to those skilled in the relevant art(s). In some embodiments, the described functions may be implemented using any one or any combination of hardware, firmware, and software.

As used herein, the terms "computer program medium" and "computer-readable medium" may generally refer to, for example, but not limited to, removable storage drive 214, a hard disk installed in hard disk drive and/or other storage device 212, and signal 228. These computer program products can provide software to computer system 200. An algorithm is herein generally considered to be a self-consistent sequence of acts or operations leading to a desired result. These sequences include physical manipulations of physical quantities. Typically, although not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated. It has proven convenient at times, primarily for reasons of common usage, to refer to these signals as bits, values, elements, symbols, characters, terms, numbers, or the like. It should be understood, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities.

Unless otherwise specifically stated, as will become apparent from the following discussion, it will be understood that throughout the specification discussion, terms such as "processing," "computing," "calculating," "determining," etc., are utilized to refer to the action and/or processing of a computer or computing system, or similar electronic computing device, to manipulate and/or convert data represented as physical (such as electronic) quantities within registers and/or memories of the computing system into other data similarly represented as physical quantities within the computing system's memories, registers, or other such information storage, transmission, or display devices.

In a similar manner, the term "processor" may refer to any device or portion of a device that processes electronic data from registers and/or memory to transform the electronic data into other electronic data that may be stored in registers and/or memory. A "computing platform" may include one or more processors.

According to an exemplary embodiment, the exemplary method presented herein may be performed by an exemplary one or more computer processors adapted to process program logic, which may be contained on an exemplary computer-accessible storage medium, and which, when executed on the exemplary one or more processors, may perform the exemplary steps presented in the exemplary method.

In some embodiments, the systems and methods for assessing neuromuscular blockade, paralysis, or neuromuscular junction status may be combined with the systems, methods, and apparatus described in U.S. Patent No. 8,731,654, entitled “SYSTEM, METHOD, APPARATUS, DEVICE AND COMPUTER PROGRAM PRODUCT FOR AUTOMATICALLY DETECTING POSITIONING EFFECT,” the entire contents of which are incorporated herein by reference. In some embodiments, the combination with the apparatus and method of the '654 patent may provide the benefits of a multifunctional system. In some cases, the apparatus and method of the '654 patent may be supplemented by the addition of one or more additional electrodes, such as stimulation electrodes on the patient's wrist, arm, or hand. The systems, methods, and apparatus may be further modified as needed in accordance with other embodiments described herein.

Methods and functions

Embodiments described herein generally relate to improved devices and methods for measuring the degree of neuromuscular blockade in a patient, typically caused by administering neuromuscular blocking agents before or during surgery, particularly within safe limits of blockade. Various embodiments relate to devices, systems, and methods for acquiring and processing recorded signals in a manner that reduces or eliminates interference from electrosurgical devices while preserving target biosignals.

The system 100 of various embodiments may include one or more features directed to automating stimulation and improving the reproducibility and fidelity of neuromuscular blockade measurements. Various exemplary features are described below.

According to an exemplary embodiment, the paralysis assessment device 104 continuously or intermittently monitors the level of neuromuscular blockade during or throughout the procedure, as directed by the user or automatically by an automated system, and adjusts the stimulation protocol. The adjustments may include one or more of the stimulation frequency, the number of stimulations delivered, or other adjustments to the applied stimulation. The stimulation protocol may be adjusted based on the current level of blockade, thereby improving the reproducibility and fidelity of the measurements.

According to an exemplary embodiment, a paralysis assessment device electrically stimulates a patient's peripheral nerves by sending electrical signals to stimulation electrodes 103 located on some or all of the patient's limbs. Recording electrodes 102, which include sensors, sense the intrinsic electrical activity of the nerves and muscles induced by the electrical stimulation. The measured amplitude or various other characteristics of the electrical activity directly correspond to the strength of the muscle response and can be used to indicate the amount of neuromuscular blockade. Thus, the effects of blockade agents on the patient during surgery can be determined. Changes in muscle electrical activity can be directly correlated with changes caused by the addition of a blocker or the administration of a block-reversing agent.

Neuromuscular blockade is typically measured using one or more standard trains of stimulation applied at a specific frequency and for a specific duration. However, various embodiments of the device may utilize stimulation applied at different frequencies or train lengths to achieve more distinct or better defined results. For example, when applying four trains of stimulation (TOF), the ratio of the fourth muscle response to the first muscle response may fall within an unclear range, such as less than 1 but greater than 0.6. In various embodiments of a typical device, this triggers the application of a series of four stimuli at progressively higher frequencies, such as 3 Hz, 4 Hz, and so on, to add additional stress to the neuromuscular junction and make its failure or integrity more apparent. As shown in Figure 3, with four stimuli at 2 Hz, the amplitude ratio of the first to the last stimulus is 0.85, which is considered a normal stimulus response within the margin of error. However, by further stressing the neuromuscular junction with higher stimulation frequencies and a larger number of stimuli, the ratio of the first to the last stimulus decreases to 0.55, clearly indicating that the junction is still not functioning at a safe transmission level. In another example, as shown in Figure 4, at 4 stimuli at 2 Hz, the amplitude ratio of the first stimulus to the last stimulus was 0.85, which is considered a normal stimulus response within the error range. By further stressing the neuromuscular junction with a higher stimulation frequency, the ratio of the first to the last stimulus increased to a ratio of 0.90, indicating that the junction is operating at a safe transmission level and no further testing is required.

Some embodiments of the present technology additionally or alternatively apply stimulation in longer trains, such as up to 8 stimulations or 12 stimulations, etc., in order to add additional stress to the neuromuscular junction and confirm the accuracy of the results, as well as make its failure or integrity more obvious.

Furthermore, in some embodiments, the devices, systems, and methods can additionally or alternatively apply stimulation in a stepwise, rapid manner such that as stimulation is applied, the stimulation intervals shrink between successive stimulations in order to add additional stress to the neuromuscular junction, making its failure or integrity more apparent.

Additional embodiments involve applying repetitive stimulation while the stimulator depolarizes the nerve to detect proximally recorded waveforms including somatosensory evoked potentials (SSEPs) and updating the neuromuscular blockade record at the onset of each SSEP average.

Other embodiments of the present technology utilize amplifiers with one or more of a CMRR > 96dB, stimulation artifact filtering, and cautery detection, which can remove confounding factors from the response.

While most devices rely on the user to initiate various types of testing, various embodiments of the devices, systems, and methods disclosed herein use automated algorithms to determine when additional resolution of the degree of block is needed, as well as when or whether additional stimulation at different frequencies or amounts is needed. For example, the algorithm can be set to perform testing at predetermined intervals based on readings below or above a desired threshold, in response to other physical parameters, in response to the phase or timing of the procedure, etc.

Some devices for measuring neuromuscular blockade rely on a direct wired connection to a processing device. In some embodiments of the present devices, systems, and methods, transmission may be via wireless signals.

Some devices also measure neuromuscular blockade based on the maximum single response from the muscle. In some embodiments disclosed herein, the devices, systems, and methods use graded progressive stimulation levels at a high stimulation rate, such as 20 Hz. In certain embodiments, the devices and methods deliver a minimum stimulation level, such as 10 mA, to a maximum stimulation level, such as 40 mA, which will induce a response from the first few active units, and a maximum stimulation level that will induce a maximum response from all active units. Using such a graded stimulation scheme can more closely follow the natural physiological response for humans when contracting muscles, and can provide greater fidelity in the measurement of neuromuscular junction function.

Some currently used devices also have problems accurately measuring the onset of evoked muscle responses because the amplifier has not recovered to baseline due to contamination by stimulation artifacts. In some embodiments, the present devices, systems, and methods can incorporate an adaptive filtering algorithm that zeros the baseline to improve the accuracy of muscle potential measurements. Figure 5a shows a stimulation artifact that has not yet recovered to baseline before the onset of the muscle response. This is improved in Figure 5b, which shows the use of an adaptive filter that removes the stimulation artifact, allowing the onset of the muscle response to be accurately measured. Importantly, the device is able to identify the onset of the potential to accurately quantify the muscle response.

The following references are hereby incorporated by reference in their entirety, and all methods, devices, systems, and components described therein may be incorporated into, substituted for, and/or combined with the systems, methods, devices, and components described herein:

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The foregoing describes in detail certain embodiments of the systems, devices, and methods disclosed herein. However, it should be understood that, no matter how detailed the above description is, these devices and methods can be implemented in many ways. As mentioned above, it should be noted that the use of specific terms when describing certain features or aspects of the technology should not be considered to mean that the terms are redefined herein to be limited to any specific features of the features or aspects of the technology associated with the term. Therefore, the scope of the present disclosure should be interpreted in accordance with the appended claims and any equivalents thereof.

Those skilled in the art will appreciate that various modifications and variations may be made without departing from the scope of the described technology. Such modifications and variations are within the scope of the embodiments defined by the appended claims. Those skilled in the art will also appreciate that components included in one embodiment are interchangeable with other embodiments; one or more portions from an illustrated embodiment may be included in any combination in other described embodiments. For example, any of the various components described herein and/or depicted in the figures may be combined with, interchanged with, or excluded from other embodiments.

Claims (16)

1. A system that follows a predetermined stimulus protocol, comprising: At least one stimulating electrode; At least one recording electrode; A pulse generator for providing stimulation to a nerve via the stimulating electrodes; and A computing device, the computing device including a processor having instructions stored thereon, wherein when executed by the computing device, the computing device: According to the stimulation protocol, the nerve is stimulated through the stimulation electrode, wherein the stimulation protocol provides multiple stimulation sequences, and the pulse frequency, frequency of each stimulation sequence, number of pulses in each stimulation sequence, or all of the above are different. The electrical response of a muscle is measured using the recording electrodes, the electrical response including amplitude; The degree of neuromuscular blockade is assessed based on the amplitude of the electrical response of the muscle during a stimulation sequence. To determine whether the stimulation protocol needs adjustment, and when consistent with programmed timing, the computing device determines whether the stimulation protocol needs adjustment at predetermined intervals based on the electrical response amplitude being above or below a threshold; and Adjust the stimulation protocol; The pulse frequency in each stimulus sequence is between 2 Hz and 10 Hz. 2. The system of claim 1, wherein assessing the degree of neuromuscular blockade comprises determining the ratio between the electrical response of the muscle from a first pulse in a stimulation sequence and the electrical response of the muscle from a final pulse. 3. The system of claim 1, wherein the number of pulses in each stimulation sequence is between 4 and 20 pulses. 4. The system of claim 3, wherein the number of pulses increases with each subsequent stimulation sequence in the stimulation scheme. 5. The system of claim 1, wherein the pulse frequency increases with each subsequent stimulation sequence in the stimulation protocol. 6. The system of claim 1, wherein the stimulation scheme comprises a first stimulation sequence of four pulses at a first frequency, a second stimulation sequence of four pulses at a second frequency higher than the first frequency, and a third stimulation sequence of four pulses at a third frequency higher than the second frequency. 7. The system of claim 6, wherein the stimulation scheme further comprises a fourth stimulation sequence of more than four pulses. 8. The system of claim 1, wherein the processor further includes instructions that, when executed by the computing device, cause the computing device to operate automatically without user input. 9. The system of claim 8, wherein the computing device automatically determines whether the stimulus protocol needs to be adjusted, and adjusts the stimulus protocol accordingly. 10. The system of claim 1, wherein the nerve is a peripheral nerve. 11. The system of claim 10, wherein the peripheral nerve is at least one of a group of nerves including an ulnar nerve, a median nerve, a peroneal nerve, and a posterior tibial nerve. 12. The system of claim 1, wherein the stimulating electrode is configured to be positioned on the patient's wrist or ankle. 13. The system of claim 1, further comprising a display unit for displaying information about the patient. 14. The system of claim 13, wherein the information is information related to the degree of neuromuscular blockade. 15. The system of claim 1, further comprising a signal amplifier to reduce factors that obscure the electrical response signal, wherein the signal amplifier comprises one or more of a CMRR >96 dB, stimulation artifact filtering, and detection of the electrocautery signal. 16. A device for assessing the degree of neuromuscular blockade, the device being configured to provide a first set of electrical stimulations to a nerve, measure the muscle response to the stimulations, determine whether the stimulation protocol needs adjustment based on the muscle response, and automatically adjust the stimulations by changing the pulse frequency in a second set of stimulations, the number of pulses in the second set of stimulations, or both; said response includes amplitude; The device follows a predetermined stimulation protocol, wherein the pulse frequency of each group of stimuli in the stimulation protocol is between 2 Hz and 10 Hz.