NeuRx Diaphragm Pacing System Clinicians Guide Rev A

TABLE OF CONTENTS INTENDED USE ... 5 GENERAL OVERVIEW... 6 WARNINGS AND CAUTIONS ... 6 ELECTROMAGNETIC INTERFERENCE WARNING... 7 FLAMMABILITY WARNING ... 7 PRECAUTIONS... 7 DESCRIPTION OF THE SYSTEM ... 8 PROCEDURE RISKS... 9 PREPARATION FOR PROCEDURE ... 10 Verifying Clinical Station Charge ... 10 OPERATING ROOM PREPARATION/ASSEMBLY ... 10 Preparation of the Electrode Delivery Tools ... 10 Patient Preparation ... 11 Establishing Laparoscopic Ports... 11 Mapping the Diaphragm ... 12 Using the Clinical Station for Mapping the Diaphragm... 14 Implantation ... 16 Routing ... 19 Final Check of Electrodes... 20 Changing Setting on the Clinical Station for Final Intraoperative Check... 20 Blocking ... 22 Apply Strain Relief Boot... 27 ESTABLISHING SETTINGS FOR A PATIENT WITH SPINAL CORD INJURY ... 32 Changing Settings on the Clinical Station... 32 Recommendations for SCI Patient without Sensation ... 34 Suggestions for making adjustments ... 34 Recommendations for SCI Patients with Sensation ... 35 ESTABLISHING SETTINGS FOR A PATIENT WITH ALS ... 36 Changing Settings on the Clinical Station... 36 Programming the NeuRx DPS® External Pulse Generator (EPG) ... 40 Confirming Settings ... 41

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Clinician’s Guide NeuRX® Diaphragm Pacing System™ Procedure & Technique Guide

Caution: Federal law restricts this device to sale by or on the order of a physician.

INTENDED USE The NeuRx® Diaphragm Pacing System™ (DPS) provides ventilatory support in patients with diaphragm dysfunction of neuromuscular origin. Diaphragm dysfunction can result in abnormal or absent respiration in patient populations of high-level spinal cord injury, central hypoventilation, amyotrophic lateral sclerosis, and other injuries or diseases affecting the neuromuscular respiratory pathways.

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GENERAL OVERVIEW This technique guide is designed as a supplement, not as a substitute, for proctorship by a certified surgeon experienced in placement of the NeuRx DPS®. It is not intended as a standalone document. The purpose of this guide is to establish clinical guidelines and practices to successfully apply the required processes to surgically implant, condition, and manage a patient with the NeuRx® Diaphragm Pacing System™ from the clinical aspect. This procedure and technique guide is not intended as a standalone document. The additional instructions of other Synapse Biomedical manuals will add clinical support and training as necessary.

WARNINGS AND CAUTIONS Caution: Federal Law (USA) restricts this device to sale, distribution and use by or on the order of a physician Caution: The long-term effects of chronic electrical stimulation are unknown. Caution: Safety has not been established for the use of the device during pregnancy. Warning: This device is electrically powered and may produce tissue damage or electrical hazard if improperly used. Warning: This device should be kept out of the reach of children. Do NOT attempt to open the NeuRx® External Pulse Generator (EPG) case; the device has NO patient-accessible controls. Doing so can result in damage to the device. Do NOT use in patients with an implanted cardiac stimulator unless a medical opinion from a specialist has first been obtained and testing for device-device interaction is performed. (Insufficient clinical data is available, at this time, to establish safety with a cardiac pacemaker). Do NOT connect the patient to high-frequency surgical equipment while connected to the EPG. Doing so can result in burns at the site of the exiting electrodes and possible damage to the EPG. Do NOT subject patients implanted with the NeuRx® Diaphragm Pacing System™ to Magnetic Resonance Imaging (MRI). Do NOT use this device if skin in the electrode implant area is swollen, infected, or inflamed or if there are skin eruptions such as phlebitis, thrombophlebitis, or varicose veins. Avoid operating this device in close proximity (for example 3 feet) to shortwave or microwave therapy equipment that may produce instability in the EPG output.

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Avoid accidental contact between connected but unused applied parts (cable or leads) and other conductive parts including those connected to ground (protective earth).

ELECTROMAGNETIC INTERFERENCE WARNING Do follow the EMC information provided. The NeuRx® External Pulse Generator (EPG) needs special precautions regarding electromagnetic compatibility (EMC). Use Caution around portable and mobile RF communications equipment as these can affect the NeuRx® EPG. Do NOT use cables or accessories other than those specified. Doing so may result in increased emissions or decreased immunity of the NeuRx® EPG.

FLAMMABILITY WARNING Do NOT use the NeuRx® External Pulse Generator (EPG) in an oxygen enriched environment or near a flammable anesthetic mixture with air, oxygen or nitrous oxide. The NeuRx® EPG is not categorized as AP (anesthetic-proof) or APG (anesthetic-proof category G - gas) type of equipment.

PRECAUTIONS Individuals with cervical and upper thoracic spinal cord injuries have an increased risk for cardiac arrhythmias. During initial use of the device, patients should be closely monitored during position changes (e.g. supine, semi-supine, sitting) for the possibility of capture of the cardiac rhythm. If it is discovered that while the device is in use there is cardiac capture due to the patient’s position, the device should be immediately turned off, the patient should be placed back on mechanical ventilation, and all appropriate patient care measures should be initiated. It is recommended that facility policies and procedures regarding cardiac events be followed. Do NOT expose the device to excessive moisture or severe mechanical shock. If display indicates system failure, pain is felt at the electrode site, or device is exposed to moisture or shock, disconnect the cable and contact Synapse Biomedical. Do NOT conduct diathermy treatment or electro cauterization in the area of the implanted electrodes. Do NOT have the EPG connected during any type of electrical diagnostic treatment such as EMG or ECG. Precautions should be observed when there is a tendency to hemorrhage following acute trauma or fracture, following recent surgical procedures when muscle contraction may disrupt the healing process, or where sensory nerve damage is present.

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Some patients may experience skin irritation or hypersensitivity due to the electrical stimulation, the adhesive on the skin bandage, or the transparent dressing (Tegaderm™ and Op-Site™ are examples of transparent dressings) used over the gauze that covers the electrodes. Contact your physician or center if this occurs as irritation can usually be reduced by changing the stimulus parameters or removing the adhesive.

DESCRIPTION OF THE SYSTEM The NeuRx DPS® is an intramuscular, percutaneous, motor point diaphragm stimulation system. It is implanted using standard laparoscopic surgical techniques in an outpatient procedure. The implanted intramuscular diaphragm electrodes are connected to a four channel external pulse generator (EPG) at a percutaneous exit site. The EPG provides a capacitively coupled, charge balanced, biphasic stimulation to each electrode with a common indifferent electrode that is placed subcutaneously. The EPG controls the charge delivered through clinician programmed parameters of pulse amplitude, pulse duration, pulse frequency, pulse ramp, inspiration time, and respiratory rate. The clinician uses a clinical station to characterize electrode response to stimulation and program the EPG with the patient specific parameters. The user connects the EPG and turns it on for use; no other controls are available or necessary for operation.

Electrode Connector Electrode wires

Patient Cable NeuRx® External Pulse Generator (EPG) Connector Holder

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The NeuRx® EPG provides repetitive electrical stimulation to the implanted electrodes to cause the patient’s diaphragm to contract and move in a manner similar to natural breathing. A clinician will program the NeuRx® EPG so that it produces the right stimulation patterns the patient. If the stimulation is uncomfortable, the clinician can adjust the NeuRx® EPG to reduce or eliminate the discomfort. The user simply connects the NeuRx® EPG to the implanted electrodes and turns it on for use; no other controls are available or necessary for operation. During use, the NeuRx® EPG should be kept close to the patient’s body to avoid pulling on the cable and electrodes. The NeuRx® EPG can be placed in a pocket of the patient’s clothing, a fanny pack or simply placed on a table or other convenient location.

PROCEDURE RISKS • • • • • • •

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There is a risk of diaphragm penetration during the procedure, which could cause a condition known as capnothorax There is a risk of infection and/or inflamed tissue at the electrode implantation sites There is a risk of bleeding at the electrode implantation sites There is a risk of nerve, tissue or organ damage as a result of the procedure There is a risk that the electrode wires could break off in the body leading to reduced or intermittent diaphragm pacing or failure of the NeuRx DPS® There is a risk of cardiac arrhythmia being caused by the placement of the electrodes in the chest cavity There is a risk of skin irritation or hypersensitivity from the electrical stimulation or from the tape used with the electrodes or from the Connector Holder bandage that holds the electrode connections There is a risk that the body may not be compatible with the materials used in the electrodes and their wires There is a risk of discomfort during use of the NeuRx DPS® There is a risk that the patient may not have sufficient muscle reaction when using the NeuRx DPS® and the product may not work Do NOT use in patients with an implanted cardiac stimulator unless a medical opinion from a specialist has first been obtained and testing for device-device interaction is performed. (Insufficient clinical data is available, at this time, to establish safety with a cardiac pacemaker) This product should not be used by patients with suspected or real heart problems The safety of this device in use during pregnancy is unknown

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PREPARATION FOR PROCEDURE Verifying Clinical Station Charge: The Clinical Station should be charged the night before a planned surgery to ensure sufficient charge for the case. To check the charge of the clinical station, simultaneously press the POWER button and the LINE FEED button. Release the POWER button and after the “Synapse Biomedical” screen appears release the LINE FEED button. A printer system check and battery charge indication will be printed. [Note: a minimum of 4 stars is required to accomplish the surgical procedure.] Turn the Clinical Station off until needed. Do not use the Clinical Station while it is plugged into wall power.

OPERATING ROOM PREPARATION/ASSEMBLY Prior to beginning procedure and patient’s arrival to the operating room, verify all of the Electrode Delivery Instruments have been sterilized and are in good working condition. You may refer to the Disassembly for Cleaning/Assembly for Use Guide provided by Synapse Biomedical. The Sterile Surgical Kit is packaged in the order of use during the case. The circulating staff should remove the following items from the kit and introduce onto the sterile table: • • • •

Trocar Tubing Mapping Probe Blue Cable Set 4 Permaloc® Electrodes

Preparation of the Electrode Delivery Tools The scrub staff should preload one PermaLoc® Electrode into one of the Electrode Delivery Tools. The other Electrode Delivery Tool should not be loaded as the surgeon may want to use it to orient the entry angle of the instrument into the diaphragm. A bowl of sterile water or saline may be used to lubricate the electrodes prior to inserting into the Electrode Delivery Tool. Use a syringe filled with saline to lubricate the Electrode Delivery Tool to aid in electrode insertion. To load the Electrode Delivery Tool, squeeze the handle of the instrument so the needle is extended approximately 180 degrees and lock the needle in this position by using the trigger stop. Carefully insert the silver pin end of the electrode into the needle tip, using caution as the needle can catch the silicon sheath on the electrode. Once the silver pin clears the end of the instrument, carefully pull most of the electrode through the needle until the blue tip of the electrode nears the bevel of the needle. Place your thumb over the bevel of the needle and pull the electrode into the needle ensuring the blue tip is completely in the bevel of the needle. Verify that only metal filament [appears white due to material properties] of the IM electrode is exiting the needle tip of the electrode delivery instrument. 10

Repeat this procedure for loading electrodes into other Electrode Delivery Tools.

Patient Preparation Ask the circulating nurse to remove the white Touch Proof Extension Lead and packet of Surface Electrodes from the Sterile Surgical Kit. Open packet of surface electrodes and remove one sheet from packet. Attach the white Touch Proof Extension Lead to one of the surface electrodes.

Surface Electrode with Touch Proof Extension Lead

Once the patient is placed on the table and prior to sterile draping, ask staff to place the surface electrode on to the patient’s thigh. Extend the White Touch Proof Extension Lead away from the sterile field so you have access to it when needed for mapping the diaphragm. Place the clinical station on small surgical table that can be easily moved into position once procedure starts. It is recommended you can see the monitor to visualize diaphragm contraction. Do not make any connections to the clinical station until the surgeon is ready to begin mapping.

Establishing Laparoscopic Ports The operation is done in the supine position with no neuromuscular blocking agents. The patient’s abdomen and chest is prepped and draped in the usual sterile fashion. Four ports will need to be inserted into the abdominal cavity: one for optics, two lateral 11

working ports for the mapping probe and one epigastric port for electrode insertion instruments and the exit site from the abdominal cavity for the electrode lead wires. During this phase, any abdominal adhesions are released and gastrostomy tube tracts are removed if they are in the way of implantation of the diaphragm pacing system. The falciform ligament is divided which allows easier visualization of the medial aspect of the right diaphragm and provides an easier exit of the pacing electrodes through the epigastric port. Standard laparoscopic principles are followed with a typical setup.

4 ports insertion

Mapping the Diaphragm First, the Falciform Ligament is cut to allow better exposure and then the electronic scalpel/cauterizing instrument is removed. Proceed by connecting the trocar tubing to the lateral trocar closest to where the clinical station is set up. Both ends of the tubing are the same. One end of the Trocar Tubing should be attached to the trocar and the other end should be passed off the sterile field. Secure the Active Sensor Module (pressure transducer) to the end of the Trocar Tubing that was passed off by twisting the luer lock connection to the transducer port.

Connect the cable from the pressure transducer to the blue “SENSOR INPUT” port on the back of the Clinical Station.

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The transducer allows the clinical station to measure the change in abdominal pressure when the muscle contracts and is not a direct reflection of muscle strength. A larger number correlates to a greater diaphragm contraction and the quality of muscle contraction is also visualized. A larger number with a large part of posterior diaphragm contracting is optimal. Insert the white Touch Proof Extension Lead into the white port on the back of the clinical station labeled “REFERENCE”. Assembly of the Mapping Probe and Blue Touch Proof Cable set will occur on the sterile field and be done by the surgical team. Connect the appropriate end of the blue touch proof cable set to the end of the blue cable on the mapping probe.

The other end of the blue cable should be passed off of the sterile field and attached to the blue port labeled “#1/L1”on the back of the Clinical Station.

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Set the blue alligator clamp aside on the sterile field. This will be used to check each electrode after implantation. Move the white clamp on the suction tubing of the mapping probe closer to the mapping probe while keeping it on sterile field. Keep clamp in locked position when not in use. Standard suction tubing is then attached to the mapping probe.

Using the Clinical Station for Mapping the Diaphragm Turn on the clinical station by depressing the power button. The Clinical Station will be in “stimulator” mode. Press the “mode” button on the left side of the Clinical Station and scroll to the “SURGICAL” function.

Locate the “Enable Auto Print” button under the printer. This feature will allow you to have a documented record of diaphragm mapping. Press the “Enable Auto Print” button to record the diaphragm mapping. Record the date, patient name and location you are mapping (Right or Left).

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When the surgeon places the mapping probe on to the diaphragm, they will request a “stim”. Locate the “STIM” button in the “MAPPING” section on the lower right side of the Clinical Station. To “stim”, press the “STIM” button and tell the surgeon the number that appears on the screen. This number represents that change in abdominal pressure. Press the “NEXT SITE” button to record that number and clear the screen for the next mapping point.

The primary electrode implant site is identified at the location of maximal pressure change in each hemi-diaphragm and visualization of diaphragm muscle contraction. A secondary electrode site is identified as either a backup to the primary site or at a location in each hemi-diaphragm that recruits another phrenic nerve motor point region [e.g. anterior or posterior] of the diaphragm at a similar magnitude. The two locations on each hemi-diaphragm are then marked using a marker. The process is repeated for the opposite hemi-diaphragm. At times, there may be very low readings of a change in abdominal pressure or very little diaphragm may move. This occurs in patients with an extremely de-conditioned diaphragm or if the diaphragm has more lower neuron involvement than the preoperative tests indicated. To confirm that this is not a technical problem, proceed with the following: In conditions of LOW READING use steps 1-7 below; 1. Confirm that all connections are secure. 2. Confirm that port on trocar is open. 3. Look for electrical artifact on the anesthesia cardiac rhythm monitor to verify stimulation. 4. Confirm that no paralyzing agent was given by the anesthesiology team and, if so, confirm that it was reversed. 5. Decrease insufflation pressure which decreases the force the diaphragm will have to contract against and may allow better visualization of diaphragm movement. 6. Allow diaphragm to rest; the repeated stimulation of a deconditioned muscle will lead to fatigue 7. Use “train” if “stim” cannot be measured or visualized. a. The use of “train” to map the diaphragm will quickly fatigue the muscle. b. To initiate a Train, depress the INSP button followed by the STIM button. [A Train pulse is a stimulation lasting 1.1 seconds in duration] 15

Upon completion of mapping the four electrode sites, disassemble the mapping probe from the blue extension cable. Place the mapping probe on the sterile back table. Assemble the sterile blue alligator clamp to the blue extension cable. Secure the blue alligator clamp to the sterile field with hemostat or by clamping to the sterile drape.

Implantation Once the primary and secondary electrode sites are identified in each hemi-diaphragm, the implantation phase begins. Placement begins with the posterior electrodes. Verify that only metal filament [appears white due to material properties] of the IM electrode is exiting the needle tip of the electrode delivery instrument.

IM Electrode with skirt

[Ensure that the 5mm blue skirt is inside the needle bevel for easier introduction into the diaphragm. The blue skirt secures the IM electrode into the diaphragm muscle]. Using the handle, position the needle tip retrograde along the barrel of the instrument and introduce the instrument in the abdomen through the 12mm port. [Note that the instrument’s needle extends through a circular motion and requires 1.35” arc of free space to transverse and open.]

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Surgical Electrode Delivery Instrument

Using the handle of the instrument carefully extend the needle. Slowly advance the tip of the needle at an angle parallel to the plane of the diaphragm that results in entry into the superficial layer of the hemi-diaphragm. [Since the diaphragm is typically 3mm 4mm thick, particular attention needs to be placed on the angle to avoid entry into the thoracic cavity].

Electrode Insertion

Electrode Insertion

Externalization of the needle tip in the abdominal cavity would confirm superficial plane of entry into the diaphragm. The laparoscopic dissector may be used to assist in the positioning of the electrode at the desired site on the diaphragm. The dissector should be used to gently grasp the diaphragmatic tissue surrounding the needle to provide counter traction as the needle is retracted from the diaphragm.

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Counter Traction on IM Electrode

Using the dissector, grasp the base of the electrode exiting the diaphragm and gently pull about 5-7cm of the electrode from the instrument. Do not pull the electrode from the diaphragm. The needle of the instrument should be extended while the instrument is withdrawn from the abdomen through the trocar. Hold the electrode while the instrument is withdrawn from the trocar to ensure the electrode is not pulled out of the diaphragm. When the electrode delivery instrument is through the trocar, the electrode will be at the tip of the needle. Gently grasp the electrode with your fingers and completely remove it from the instrument. Hand the electrode delivery instrument to the scrub staff to be reloaded in preparation for the next side. The silver end of the electrode will be out of the trocar. Take the blue alligator clamp and connect it to the silver electrode tail. The Clinical Station operator will run a STIM test to verify muscle twitch and a Train test to verify full muscle contraction. Readings of A, B, or C denotes acceptable connection [A superior, B strong, C acceptable]. If the response is an X [open circuit or unacceptable resistance], reposition the alligator clamp ensuring that alligator clamp is making good contact with the silver pin [avoiding the silicon sleeve] and retest. If the response is still “X”, then use a 5mm dissector to manipulate the electrode and retest again. If the response continues to be an X, the electrode may need to be removed and a new electrode may need to be introduced into the diaphragm. The second IM electrode is inserted in a similar fashion and tested to confirm appropriate contraction of the hemi-diaphragm. The procedure is repeated now on the opposite hemi-diaphragm.

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After all electrodes are implanted, all 4 leads are carefully brought out through the 12 mm trocar, separated and marked with steri-strips® noting the right and left side. The 12mm trocar is then removed.

IM Electrodes Exit

Routing Use a local anesthetic around 12 mm port entrance site and the marked exit sites before tunneling. Four tunnelers are passed subcutaneously to an acceptable location on the patient’s chest or abdomen in a vertical line. An additional indifferent electrode is placed subcutaneously in the most inferior or caudad location with a separate tunneler and percutaneous exit site. The tunnelers are then flushed to enable the electrodes to pass through the lumen. In a standard fashion, the two left electrodes are fed down the two cephalad tunnelers and then the two right electrodes in the more caudad tunnelers.

Tunneling IM electrodes

The steri-strips® are removed, the IM electrodes are fed down the tunnelers cannula and the exit sites are marked [L, L, R, R, A]. At this time, the abdomen is once again insufflated and the excess leads are retracted into the abdomen and placed immediately over the liver, away from any of the bowel. The leads need to be approximately 1.5” exiting the chest and a final system check will be conducted.

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Final Check of Electrodes The Clinical Station now needs to be in the “STIMULATOR” mode and placed to maximal stimulus settings (increase Pulse Width to 200us) to check for cardiac interaction. To do this, press the “MODE” until the “STIMULATOR” mode is indicated on the screen.

Changing Setting on the Clinical Station for Final Intraoperative Check Place the clinical station in “STIMULATOR” mode by using the “MODE” button. Note that the clinical station will default to this mode and the selector will be on Channel 1 when it is turned on. The clinical station will display default setting of AMP = 25mA, Pulse Width = 100μs, Respiration = 12 BPM, Inspiration Time = 1.1 seconds, Frequency = 20Hz, Pulse Ramp = 0. Adjusting Pulse Width: 1. Under “STIMULUS SETTINGS”, press the “PW” button. You will notice a flashing block over the number 0 in 100us.

2. To increase pulse width, use the up arrow (▲). a. Maximum pulse width setting is 200us. 3. To decrease pulse width, use the down arrow (▼). a. Minimum pulse width setting is 20us. 4. When finished with the adjustments, press the “SELECT’ button and the indicator will move to the next channel. 5. All four channels need to be set for 200us and the select button is pressed to have the indicator point to each channel.

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Introduce the colored cables into the sterile field in the following order: green, orange, yellow and white. Connect in the following sequential order the alligator clamps to the silver pin on the designated electrodes; 1. Blue to 1st left IM electrode 2. Green to 2nd left IM electrode 3. Orange to 1st right IM electrode 4. Yellow to the 2nd right electrode 5. White to the indifferent electrode Connect each cable to the respective matching colored port on the Clinical Station.

Each lead is checked sequentially by depressing the number 1, 2, 3, 4 in order and noting readings of A, B, C, or X. Then depress the “LEFT” button to stimulate the left hemi-diaphragm followed by the “RIGHT” button. Check all leads by pressing the “ALL” button. These buttons are found in the “STIMULUS ACTIVATE” section of the clinical station.

To pace all the leads, press the “BPM” button and then the “ALL” button. The clinical station will now be stimulating the entire diaphragm and the patient is now pacing at 12 breaths per minute (BPM).

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An ECG strip is recorded with all four electrodes active to be sure there is no capture of the cardiac rhythm. In the event of cardiac rhythm capture, the stimulus must be stopped immediately and the intensity level and electrode combination must be noted. The identified electrode or electrodes must not be used and the surgical team should terminate the electrodes and locate another motor point that does not interrupt the cardiac rhythm. During initial use of the device, patients should be closely monitored during position changes (e.g. supine, semi-supine, sitting) for the possibility of capture of the cardiac rhythm. If it is discovered that while the device is in use there is cardiac capture due to the patient’s position, the device should be immediately turned off, the patient should be placed back on mechanical ventilation, and all appropriate patient care measures should be initiated. It is recommended that facility policies and procedures regarding cardiac events be followed. If it is discovered that there is capture of the cardiac rhythm by the device, for any reason, the identified electrode or electrodes on the patient’s device should be programmed “OFF”. It will be at the discretion of the medical team to interrogate the device under controlled settings (e.g. cardiology lab) or to terminate the electrodes at the skin to prevent further use. Once it is determined that there is no cardiac capture, you may request someone from the anesthesia team to discontinue ventilation while the patient is being paced and note tidal volume on the anesthesia record. Then reinitiate ventilation, gently disconnect the clamps from the electrodes and turn off the clinical station. Cover the exiting electrodes with a 4 x 4 dressing and secure with an occlusive dressing. At the conclusion of the case, it is recommended that a chest x-ray be obtained to verify that no intra-abdominal CO2 has entered into the chest cavity (capnothorax). If a capnothorax is present, it can be resolved with deep tidal volumes by Anesthesia [deep breathing] and, if clinically indicated, aspirated with a percutaneous catheter at the end of the surgery.

Blocking Blocking is the final process of preparing the wires to allow connection to the NeuRx DPS® and its connection cable. Blocking can be done in the Operating Room or in Recovery. [CAUTION: When performing this step, avoid pulling excess electrode from the exit site. Excessive externalized electrode from the exit site could lead to accidental electrode breakage.]

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