Safety Information

INTENDED USE / INDICATION

CONTRAINDICATIONS

Vagotomy — The VNS Therapy system cannot be used in patients with a bilateral or left cervical vagotomy.

Diathermy — Do not use shortwave diathermy, microwave diathermy, or therapeutic ultrasound diathermy (hereafter referred to as diathermy) on patients implanted with a VNS Therapy system.

WARNINGS — ALL IMPLANTS

Use — The VNS Therapy system should only be prescribed and monitored by physicians who have specific training and expertise in the management of seizures and the use of this device. It should only be implanted by physicians trained in surgery of the carotid sheath who have received specific training in implantation of this device.

Not a Cure — Physicians should warn patients that VNS Therapy is not a cure for epilepsy. Because seizures may occur unexpectedly, patients should consult with a physician before engaging in unsupervised activities that could harm themselves or others (e.g., driving, swimming, bathing, or participating in strenuous sports).

Safety and Efficacy Not Established — The safety and efficacy of the VNS Therapy system have not been established for uses outside its approved indications. Safety and efficacy have not been shown for people with the following conditions: cardiac arrhythmias or other abnormalities; history of dysautonomias; history of previous therapeutic brain surgery or CNS injury; 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; or progressive neurological diseases other than epilepsy.

Dysfunctional Cardiac Conduction Systems — The safety and effectiveness of the VNS Therapy system in patients with predisposed dysfunction of cardiac conduction systems (re-entry pathways) have not been established. Evaluation by a cardiologist is recommended if family history, patient history, or electrocardiogram suggests an abnormal cardiac conduction pathway. Serum electrolytes, magnesium, and calcium should be documented before implantation. Postoperative bradycardia may occur in patients with certain underlying cardiac arrhythmias. Post-implant electrocardiograms and Holter monitoring are recommended if clinically indicated.

Bradycardia or Asystole During Implantation — Recommended implantation procedures and intra-operative product tests described in the Implantation Procedure Overview should be followed. During intra-operative System Diagnostics, infrequent incidents of bradycardia and/or asystole have occurred. If asystole, severe bradycardia (heart rate < 40 bpm), or a clinically significant change in heart rate is encountered during diagnostics or initiation of stimulation, physicians should be prepared to follow Advanced Cardiac Life Support (ACLS) guidelines.

External Defibrillation or Cardioversion (electrical) — External defibrillation or cardioversion procedures may damage the generator and may temporarily or permanently damage the nerve. To minimize current flow through the generator and lead system: position defibrillation patches or paddles perpendicular to the generator and lead system and as far from the generator as possible; use the lowest clinically appropriate energy output; and confirm generator function after any defibrillation or cardioversion.

Magnetic Resonance Imaging (MRI) — MRI procedures should only be performed as described in the MRI Guidance instructions for use. In some cases, surgery may be required to remove the VNS Therapy system if scanning with a transmit RF body coil is needed.

MR Unsafe Devices — The Wand, Programmer, and patient magnet are MR Unsafe devices and must not be brought into the MRI scanner room.

Excessive Stimulation — Excessive stimulation is defined as the combination of an excess duty cycle (ON time greater than OFF time) and high-frequency stimulation (≥ 50 Hz). Excessive stimulation has resulted in degenerative nerve damage in laboratory animals.

Device Manipulation — Manipulation of the generator or lead through the skin (Twiddler’s Syndrome) may damage or disconnect the lead and potentially injure the vagus nerve. For Model 1000 and Model 1000-D devices, recalibration of prone position detection may be required. Patients, parents, and caregivers should be warned against device manipulation.

Swallowing Difficulties — Dysphagia may occur during active stimulation, and aspiration may result from increased swallowing difficulties. Patients with pre-existing swallowing difficulties or a history of drooling or hypersalivation are at greater risk. Appropriate aspiration precautions should be taken. Temporarily stopping stimulation with the magnet while eating may mitigate this risk.

Dyspnea or Shortness of Breath — Dyspnea may occur during active VNS Therapy. Patients with underlying pulmonary disease or insufficiency, such as chronic obstructive pulmonary disease or asthma, may be at increased risk and should be evaluated prior to implantation and monitored following initiation of stimulation.

Obstructive Sleep Apnea (OSA) — Patients with OSA may experience an increase in apneic events during stimulation. Lowering stimulus frequency or increasing OFF time may prevent exacerbation. Vagus nerve stimulation may also cause new-onset sleep apnea. Patients at risk for OSA should undergo appropriate evaluation prior to implantation.

Device Malfunction — Device malfunction may cause painful stimulation or direct current stimulation, potentially leading to nerve damage. Patients, parents, and caregivers should be instructed to use the magnet to stop stimulation if a malfunction is suspected and to contact their physician immediately. Surgical intervention may be required.

Sudden Unexplained Death in Epilepsy (SUDEP) — SUDEP rates observed in VNS Therapy patients through August 1996 and February 2005 are detailed based on patient-years of exposure. Although observed rates exceed those of a healthy population, they fall within the reported range for epilepsy patients not receiving vagus nerve stimulation.

WARNINGS — GENERATORS

Generators with AutoStim: Cardiac Arrhythmia — AutoStim Mode should not be used in patients with clinically meaningful arrhythmias managed by devices or treatments that interfere with intrinsic heart rate responses (e.g., pacemaker dependency, implantable defibrillators, beta-blockers), or in patients with chronotropic incompetence and sustained bradycardia (< 50 bpm).

PRECAUTIONS — ALL IMPLANTS

Physician Training — Prescribing physicians should be experienced in epilepsy diagnosis and treatment and familiar with programming and use of the VNS Therapy system.

Use During Pregnancy — Safety and effectiveness during pregnancy have not been established.

Effects on Other Medical Devices — The VNS Therapy system may affect other implanted devices, including pacemakers and defibrillators. Careful programming may be required. When multiple stimulators are implanted, they should be placed at least 10 cm (4 inches) apart to avoid interference.

Device Reset — For Models 103 through 1000-D, reset disables stimulation output while preserving settings and device history. For Models 102 and 102R, reset programs the device OFF (output current = 0 mA) and causes loss of all device history, which should be documented prior to reset.

PRECAUTIONS — GENERATOR AND LEAD

Unintended Stimulation — For devices that sense changes in heart rate, false positive detections may result in unintended stimulation. Examples of situations in which heart rate may increase include exercise, physical activity, and normal autonomic changes in heart rate, both while awake and asleep.

Battery Depletion or Drain (Generators with AutoStim)  — Patients should be informed about the AutoStim feature. Use of this feature will reduce battery longevity and may require more frequent generator replacements. Because AutoStim can significantly affect battery life, patients should return for follow-up visits at appropriate intervals to assess whether they are receiving benefit from the current AutoStim settings.

Battery Depletion or Drain (Model 102 and Model 102R) — Frequencies of 5 Hz or below should not be used for long-term stimulation.

Scheduled Programming (Model 1000 and Model 1000-D) — Because this feature allows therapy increases at scheduled intervals, it may not be appropriate for patients who are nonverbal or unable to use the patient magnet to stop undesired stimulation. Caution should also be exercised when using this feature in patients with a history of obstructive sleep apnea, shortness of breath, coughing, swallowing difficulties, or aspiration.

PRECAUTIONS — RELATED TO IMPLANTATION

Vagus Nerve Placement — The VNS Therapy system is indicated only for stimulation of the left vagus nerve in the neck within the carotid sheath, below the point where the superior and inferior cervical cardiac branches separate from the vagus nerve. Safety and efficacy have not been established for stimulation of the right vagus nerve or of any other nerve, muscle, or tissue.

Reversal of Lead Polarity — Reversal of lead polarity has been associated with an increased risk of bradycardia in animal studies. Electrodes must be attached to the left vagus nerve in the correct orientation.

Device Placement — For generators with AutoStim, the physical location of the device is critical to accurate heartbeat sensing. Care must be taken to follow the implant location selection process outlined in the Implantation Procedure. This process may be performed pre-operatively as part of the patient’s surgical work-up.

Infection Control — Strict adherence to infection control procedures is essential. Infections associated with implanted devices are difficult to treat and may require device explantation. Patients should receive pre-operative antibiotics, and surgeons should ensure all instruments are sterile. Children under 12 years of age may be at greater risk for infection compared with adolescents and adults. Careful monitoring for infection and avoidance of manipulation of the surgical site should be emphasized.

Lead Stabilization — Use of a neck brace during the first week after implantation may help ensure proper lead stabilization.

Programming After Surgery — The VNS Therapy system should not be programmed to ON or periodic stimulation for at least 14 days following initial or replacement implantation. Failure to observe this precaution may result in patient discomfort or adverse events.

Laryngeal Irritation — Laryngeal irritation may occur during stimulation. Patients who smoke may be at increased risk.

PRECAUTIONS — HOSPITAL AND MEDICAL ENVIRONMENTS

VNS Therapy System Operation —Device diagnostics should always be performed following any of the procedures described below.

Mammography — Special patient positioning may be required to obtain clear images due to the location of the generator in the chest.

Therapeutic Radiation — Therapeutic radiation, including exposure from cobalt machines or linear accelerators, may damage generator circuitry. Radiation effects are cumulative and may result in temporary disturbance or permanent damage that may not be immediately detectable.

Electrosurgery — Use of electrosurgery devices, including electrocautery or radiofrequency ablation, may damage the generator.

Extracorporeal Shockwave Lithotripsy — This procedure may damage the generator. If therapeutic ultrasound is required, the generator should not be positioned in a water bath or otherwise exposed. If unavoidable, the generator should be programmed to 0 mA during treatment and reprogrammed to original settings afterward.

Treatment That Involves Electrical Currents — For treatments involving electrical current passing through the body (e.g., TENS units), the generator output should be set to 0 mA or its function closely monitored during initial treatment.

Therapeutic Ultrasound — Routine therapeutic ultrasound may damage the generator and could be inadvertently concentrated by the device, causing harm. Diagnostic ultrasound has no known adverse effects on the generator or lead.

Magnetic Resonance Imaging (MRI) — MRI using a transmit RF body coil should not be performed for certain VNS Therapy device configurations or conditions. Lead heating may result in serious injury. MRI electromagnetic fields may reset generator parameters or activate the device if Magnet Mode output remains ON.

Receive RF Coils — Some MR head coils operate in receive-only mode and require use of the transmit RF body coil. The use of receive-only coils does not alter hazards associated with transmit RF body coils.

Transmit RF Coils — Exposure of the VNS Therapy system to any transmit RF coil must be avoided. MRI scans using transmit RF coils must not be performed in defined exclusion zones.

PRECAUTIONS — HOME OCCUPATIONAL ENVIRONMENTS

Avoid Strong Electric or Magnetic Fields — Patients should use reasonable caution to avoid strong electric or magnetic fields. If generator operation ceases due to electromagnetic interference, moving away from the source may allow normal operation to resume.

ADVERSE EVENTS

CYB 03089/2 (CE English)