Safety Information

Indication for use

The MicroTransponder® Vivistim® Paired VNS™ System is intended to be used to stimulate the vagus nerve during rehabilitation therapy in order to reduce upper extremity motor deficits and improve motor function in chronic ischemic stroke patients with moderate to severe arm impairment.

Contraindications

The Vivistim® System cannot be used in patients after a bilateral or left cervical vagotomy.

Warnings

Clinicians should inform patients about all potential risks and adverse events discussed in the Vivistim manual and the other system manuals.

Use—The Vivistim® System should only be prescribed and monitored by clinicians who have specific training and expertise in the management of stroke and the use of this device. The system should only be implanted by physicians who are trained in surgery of the carotid sheath and have received specific training in the implantation of this device. The IPG, Lead, WT, and SAPS should only be used as part of MicroTransponder’s Vivistim® System.
Not curative—Clinicians should warn patients that the Vivistim® System has not been determined to be a cure for upper extremity motor deficits associated with ischemic stroke. Patients should be counseled to understand that individual results will likely vary. Beneficial results might not become evident for months or may never occur.
Unapproved uses—The safety and efficacy of the Vivistim® System have not been established for uses outside the Intended Use / Indication section of the Vivistim manual, including, but not limited to, patients with:
- Acute suicidal thinking or behavior
- History of schizophrenia, schizoaffective disorder, or delusional disorders
- History of rapid cycling bipolar disorder
- History of previous therapeutic brain surgery or CNS injury
- Progressive neurological diseases other than stroke
- Cardiac arrhythmias or other abnormalities
- History of dysautonomias
- History of respiratory diseases or disorders, including dyspnea and asthma
- History of ulcers (gastric, duodenal, or other)
- History of vasovagal syncope
- Only one vagus nerve
- Other concurrent forms of brain stimulation
- Pre-existing hoarseness
Diathermy—Do not use shortwave diathermy, microwave diathermy, or therapeutic ultrasound diathermy (thereafter referred to as diathermy) on patients implanted with a Vivistim® System. Diagnostic ultrasound is not included in this contraindication. Energy delivered by diathermy may be concentrated into or reflected by implanted products such as the Vivistim® System. This concentration or reflection of energy may cause heating. Heating of the Vivistim® System resulting from diathermy could cause temporary or permanent nerve, tissue, or vascular damage. This damage may result in pain or discomfort, loss of vocal cord function, or even possibly death if there is damage to blood vessels. Because diathermy can concentrate or reflect its energy off any size implanted object, the hazard of heating is possible when any portion of the Vivistim® System remains implanted, including just a small portion of the Lead or electrode. Injury or damage can occur during diathermy treatment whether the Vivistim® System is turned on or off. Diathermy is further prohibited because it may also damage the Vivistim® System components resulting in loss of therapy, requiring additional surgery for system explantation and replacement. All risks associated with surgery or loss of therapy would then be applicable.
Advise patients to inform all healthcare professionals that they should not be exposed to diathermy treatment.
Worsening depression/suicidality—Patients being treated with adjunctive Paired VNS™ who have moderate or severe depression should be observed closely for clinical worsening and suicidality, especially at the time of Paired VNS™ stimulation parameter changes or drug or drug dose changes, including either increases or decreases in the stimulation parameters or concomitant treatments. Consideration should be given to changing the therapeutic regimen of Paired VNS™ or concomitant treatments, including possibly discontinuing Paired VNS™ or the concomitant therapy, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient’s presenting symptoms.
Dysfunctional cardiac conduction systems—The safety and effectiveness of the Vivistim® System in patients with predisposed dysfunction of cardiac conduction systems (re-entry pathway) have not been established. Evaluation by a cardiologist is recommended if the family history, patient history, or electrocardiogram suggests an abnormal cardiac conduction pathway. Serum electrolytes, magnesium, and calcium should be documented before implantation. Additionally, postoperative bradycardia can occur among patients with certain underlying cardiac arrhythmias. Post-implant electrocardiograms and Holter monitoring are recommended if clinically indicated. It is important to follow recommended implantation procedures and intraoperative product testing described in the Recommendations for Implantation section of the Vivistim manual. During intraoperative Lead Impedance Diagnostics of other vagus nerve stimulation systems, infrequent incidents of bradycardia and/or asystole can occur. If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is encountered during a Lead Impedance Check or during initiation of stimulation, physicians should be prepared to follow guidelines consistent with Advanced Cardiac Life Support (ACLS). Additionally, postoperative bradycardia or asystole has been reported rarely in epilepsy and depression patients receiving VNS Therapy® (although none have been reported as of June 8, 2020, with Paired VNS™). If a patient has experienced asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate, the patient should be placed on a cardiac monitor. The safety of this therapy has not been systematically established for patients experiencing bradycardia or asystole during Paired VNS.
Swallowing difficulties—Difficulty swallowing (dysphagia) may occur with active stimulation, and aspiration may result from the increased swallowing difficulties. Patients with pre-existing swallowing difficulties are at greater risk for aspiration. Appropriate aspiration precautions should be taken for such patients.
Dyspnea or shortness of breath—Dyspnea (shortness of breath) has not been reported with Paired VNS™ but has been reported with VNS Therapy®. Any patient with underlying pulmonary disease or insufficiency, such as chronic obstructive pulmonary disease or asthma, may be at increased risk for dyspnea and should have their respiratory status evaluated prior to implantation and monitored following initiation of stimulation.
Obstructive sleep apnea—Although worsened apnea has not been reported with Paired VNS™, it has been reported with VNS Therapy®. Patients with obstructive sleep apnea (OSA) may have an increase in apneic events during stimulation. Lowering stimulus frequency or increasing the Train Period may prevent exacerbation of OSA. Vagus nerve stimulation may also cause new onset sleep apnea in patients who have not previously been diagnosed with this disorder. It is recommended that patients being considered for Paired VNS™ who demonstrate signs or symptoms of OSA, or who are at increased risk for developing OSA, should undergo the appropriate evaluation(s) prior to implantation.
Device malfunction—Device malfunction could cause painful stimulation or direct current stimulation. Either event could cause nerve damage and other associated problems. Patients should be instructed to end the current therapy session and/or use the magnet to stop stimulation if they suspect a malfunction, and then to contact their clinician immediately for further evaluation. Prompt surgical intervention may be required if a malfunction occurs.
Magnetic resonance imaging (MRI)—Reference the MRI Safety Information section of the Vivistim manual.
Excessive stimulation—Excessive stimulation at an excess duty cycle (when “on” time is greater than “off” time) has resulted in degenerative nerve damage in laboratory animals.
Device manipulation—Patients who manipulate the IPG and Lead through the skin (Twiddler’s Syndrome) or who have significant chest tissue causing significant movement of the IPG may damage or disconnect the Lead from the IPG and/or possibly cause damage to the vagus nerve. Patients should be warned against manipulating the IPG and Lead.

NOTE: See the Clinician Training / Information section of the instructions for use

Surgery—Post surgery, patients may commonly experience pain, swelling, and/or tenderness at the surgery site. Other risks of VNS surgery include bleeding, seroma/hematoma, bruising, permanent numbness or other sensations, vocal cord paralysis (VCP), itching, infection, and allergic response to the implanted materials. A detailed list of expected adverse events is included below.
Adjacent Equipment—Use of this equipment adjacent to or stacked with other equipment should be avoided because it could result in improper operation. If such use is necessary, this equipment and the other equipment should be observed to verify that they are operating normally.
Accessories—Use of accessories, transducers and cables other than those specified or provided by the manufacturer of this equipment could result in increased electromagnetic emissions or decreased electromagnetic immunity of this equipment and result in improper operation.”
Medications—It is possible that some medications may interfere with the mechanism of action of VNS and may therefore impact effectiveness of the therapy. Effectiveness has not been established in patients taking: Scopolamine, Atropine, Biperiden (Trihexyphenidyl and Cycrimine, Benztropine and Procyclidine), Prazosin, Clonidine, Tizanidine, Propranolol, Oxprenolol and Metoprolol, Dextromethorphan, Amantadine and Memantine, Haloperidol, Lorazepam, and Lamotrigine.

Precautions

Clinicians should inform patients about all potential risks and adverse events discussed in the Vivistim manual.

Appropriate training is very important. Prescribing clinicians should be experienced in the management and treatment of stroke and should be familiar with the programming and use of the Vivistim® System.
Physicians who implant the Vivistim® System should be experienced performing surgery in the carotid sheath and should be trained in the surgical technique relating to implantation of the MicroTransponder® Vivistim® System.
Use during pregnancy—The safety and effectiveness of the Vivistim® System have not been established for use during pregnancy. There are no adequate and well-controlled studies of Paired VNS™ in pregnant women.
The Vivistim® System is indicated for use only in stimulating the left vagus nerve in the neck area inside the carotid sheath. The Vivistim® System is indicated for use only in stimulating the left vagus nerve below where the superior and inferior cervical cardiac branches separate from the vagus nerve. The safety and efficacy of the Vivistim® System have not been established for stimulation of the right vagus nerve or of any other nerve, muscle, or tissue.
It is important to follow infection control procedures. Infections related to any implanted device are difficult to treat and may require that the device be explanted. The patient should be given antibiotics preoperatively. The surgeon should ensure that all instruments are sterile prior to the operation.
Frequent irrigation of both incision sites with generous amounts of bacitracin or equivalent solution should be performed prior to closure. To minimize scarring, these incisions should be closed with cosmetic closure techniques. Also, antibiotics should be administered postoperatively at the discretion of the physician.
Effects on other medical devices—The Vivistim® System has not been tested with and may affect the operation of other implanted devices, such as cardiac pacemakers and implanted defibrillators. Possible effects include, but are not limited to, sensing problems and inappropriate device responses.
Reversal of Lead polarity has been associated with an increased chance of bradycardia in animal studies of unpaired VNS. It is important that the electrodes are attached to the left vagus nerve in the correct orientation.
The patient can use a neck brace for the first week to help ensure proper Lead stabilization.
A reset of the device will program the device off (output current = 0.0 mA). When an IPG is reset, its stimulation output is disabled (0.0 mA); however, all settings and device history are preserved. After a successful reset, the IPG stimulation output may be reprogrammed from 0.0 mA as appropriate for the patient to resume operation at their previously programmed settings.

NOTE: For more information on diagnostic testing, see the Troubleshooting section of the instructions for use.

Laryngeal irritation may result from stimulation. Patients who smoke may have an increased risk of laryngeal irritation.
Potential effects of Lead breaks—Lead fractures may prevent patients from receiving therapy. If a Lead fracture is suspected, perform diagnostic testing to evaluate continuity within the system. If diagnostic testing suggests that a fracture is present, consider turning the Paired VNS™ IPG to 0.0 mA of output current. Continuing stimulation with a fractured Lead may result in dissolution of the conductor material resulting in adverse events, such as pain, inflammation, and vocal cord dysfunction. The benefits and risks of leaving the Paired VNS™ IPG on (actively stimulating) when a Lead fracture is present should be evaluated and monitored by the medical professional treating the patient.
Some complications may be associated with damage to the vagus nerve.
- Hoarseness may be caused by device malfunction, nerve constriction, or nerve fatigue. Nerve constriction should be apparent within a few days after implantation and may require explantation of the Lead. Nerve fatigue usually occurs after intense stimulation parameters have been used and might not be associated with any other adverse event. If fatigue is suspected, use of the Vivistim® IPG should be discontinued for several days until hoarseness subsides.
- Persistent hoarseness not associated with stimulation suggests possible nerve irritation and should be immediately investigated.
- Trauma to the vagus nerve at the implantation site could result in permanent vocal cord dysfunction or other difficulties due to a damaged nerve.
Metal objects implanted in the patient near the IPG may interfere with device communication.
Objects implanted near the IPG or Lead (typically from a separate medical procedure) may migrate and damage the IPG or Lead.

Adverse Events

Adverse events can be found in the Vivistim® System labeling. NOTE: Most stimulation related adverse event can be mitigated by reducing stimulation settings.

Potential complications associated with surgical implantation or use of the device, regardless of whether reported in clinical studies, include:

Allergic and/or rejection response to the implanted materials
Damage to blood vessels in the vicinity of implant
Discomfort from the stimulation (such as pain or muscle movement)
Excessive bleeding associated with implant surgery
Fibrosis to the extent that it makes it difficult to remove the system without damaging surrounding structures
Infection at implant site(s)
Local irritation, seroma, hematoma, erosion, or swelling
Nerve trauma or damage causing hoarseness, facial palsy, or other effects due to vagus nerve or surrounding nerve damage during implantation
Other acute symptoms (i.e., coughing, hoarseness, etc. due to stimulation)
Persistent pain, numbness, or inflammation at the implant site
Problems with swallowing or hoarseness
Undesirable change in stimulation over time, possibly related to tissue changes around the electrode(s), Lead or IPG migration, loose electrical connections, or Lead fractures – any of which may require a corrective surgery
Local irritation, seroma, hematoma, erosion, or swelling
Nerve trauma or damage causing hoarseness, facial palsy, or other effects due to vagus nerve or surrounding nerve damage during implantation
Other acute symptoms (e.g., coughing, hoarseness, etc., due to stimulation)
Persistent pain, numbness, or inflammation at the implant site
Problems with swallowing or hoarseness
Undesirable change in stimulation over time, possibly due to tissue changes around the electrode(s), Lead or IPG migration, loose electrical connections, or Lead fractures, any of which may require a corrective surgery

Events most commonly reported as at least possibly related to stimulation were coughing, hoarseness, throat irritation, and pain. Most stimulation related adverse event can be mitigated by reducing stimulation settings.

Rx Only. Refer to the product labeling for a detailed disclosure of specific indications, contraindications, warnings, precautions and adverse events.