Aurora BioScience Neurology

VNS Therapy for Pharmacoresistant Epilepsy

 

This resource is intended to provide specific information regarding VNS Therapy™ and pharmacoresistant epilepsy for physicians, nurses and other healthcare professionals.

 

 

Safety and Prescribing Information

 

 

Indications for Use

 

The VNS Therapy System is indicated for use as an adjunctive therapy in reducing the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or without secondary generalisation) or generalised seizures that are refractory to antiepileptic medications.

 

 

The VNS Therapy System cannot be used in patients after a bilateral or left cervical vagotomy.

Do not use short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy on patients implanted with the VNS Therapy System. Diagnostic ultrasound is not included in this contraindication.

 

 

Warnings

 

Physicians should inform patients about all potential risks and adverse events discussed in the Physician’s Manual. This is not intended to serve as a substitute for the complete Physician’s Manual.

The safety and efficacy of the VNS Therapy System has not been established for uses not covered in the “Intended Use / Indications” section of the Physician’s Manual.

The safety and efficacy of the VNS Therapy System treatment has not been established for stimulation of the right vagus nerve or of any other nerve, muscle, or tissue.
 

 

Excessive stimulation at a combination of high frequency (50 Hz) and an excess duty cycle (that is, one that occurs when ON time is greater than OFF time) has resulted in degenerative nerve damage in laboratory animals. An excess duty cycle can be produced by continuous or frequent magnet activation (> 8 hours), as determined by animal studies. Cyberonics recommends against stimulation at these combinations of ranges.

Aspiration may result from the increased swallowing difficulties reported by some patients during stimulation. Patients who have pre-existing swallowing difficulties are at greater risk for aspiration.

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 use the magnet to stop stimulation if they suspect a malfunction, and then to contact their physician immediately for further evaluation. Prompt surgical intervention may be required if a malfunction occurs.

Susceptible patients with predisposed dysfunction of cardiac conduction systems (re-entry pathway) have not been studied as part of controlled clinical trials to establish the safety of VNS Therapy system treatment in these patients. 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. Post-implant electrocardiograms and Holter monitoring are recommended if clinically indicated.

Sudden unexplained death in epilepsy (SUDEP): Through August 1996, 10 sudden and unexplained deaths (definite, probable, and possible) were recorded among the 1,000 patients implanted and treated with the VNS Therapy device. During this period, these patients had accumulated 2,017 patient-years of exposure. Some of these deaths could represent seizure-related deaths in which the seizure was not observed, at night, for example. This number represents an incidence of 5.0 definite, probable, and possible SUDEP deaths per 1,000 patient-years. Although this rate exceeds that expected in a healthy (nonepileptic) population matched for age and sex, it is within the range of estimates for epilepsy patients not receiving vagus nerve stimulation, ranging from 1.3 SUDEP deaths for the general population of patients with epilepsy, to 3.5 (for definite and probable) for a recently studied antiepileptic drug (AED) clinical trial population similar to the VNS Therapy System clinical cohort, to 9.3 for patients with partial onset epilepsy.
 

The VNS Therapy System is not curative: Physicians should warn patients that the VNS Therapy System is not a cure for epilepsy and that since seizures may occur unexpectedly, patients should consult with a physician before engaging in unsupervised activities, such as driving, swimming and bathing, and in strenuous sports that could harm them or others.

Obstructive Sleep Apnea: Patients with obstructive sleep apnea (OSA) may have increased apneic events during stimulation. Cyberonics recommends care when treating patients with pre-existing OSA. Lowering stimulus frequency or prolonging OFF time may prevent exacerbation of OSA.
 

 

Precautions

 

Physicians should inform patients about all potential risks and adverse events discussed in the Physician’s Manual.

Laryngeal irritation may result from stimulation. Patients who smoke may have an increased risk of laryngeal irritation.

Dyspnea may result from stimulation. Patients with chronic obstructive pulmonary disease may have an increased risk of dyspnea.

It is important to follow recommended implantation procedures and intraoperative product testing described in this manual. During the intraoperative Lead Test, rare incidents of bradycardia and/or asystole have occurred. As of October 1998, approximately 3,000 patients had been implanted with the VNS Therapy System. Four of these patients were reported to have experienced bradycardia and/or asystole during the intraoperative Lead Test. All four patients recovered without sequelae. One of the four patients was implanted with the VNS Therapy System. There were no postoperative or VNS-treatment-related cardiac adverse events later reported for that patient. No similar events were reported to have occurred during the clinical studies at the time of implantation or during treatment. The safety of this therapy has not been systematically established for patients experiencing bradycardia or asystole during VNS Therapy System implantation.

Reversal of lead polarity has been associated with an increased chance of bradycardia in animal studies. When using the Model 300 Bipolar Lead, it is important to make sure that the dual lead connector pins are correctly inserted (white marker to + connection) into the pulse generator header.

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. Cyberonics recommends that the patient be given antibiotics preoperatively. The surgeon should ensure that all instruments are sterile prior to the operation.

The information contained in this Brief Summary for Physicians represents partial excerpts of important prescribing information taken from the Physician’s Manual. The information is not intended to serve as a substitute for a complete and thorough understanding of the material presented in all of the Physician’s Manuals for the VNS Therapy System and its component parts, nor does this information represent full disclosure of all pertinent information concerning the use of this product, potential safety complications or efficacy outcomes.

The VNS Therapy System is indicated for use only in stimulating the left vagus nerve in the neck area inside the carotid sheath.

The VNS Therapy 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. A neck brace can be used by the patient for the first week to help ensure proper Bipolar Lead stabilisation.
 

Environmental and Medical Therapy Hazards
Patients should exercise reasonable caution in avoiding devices that generate a strong electric or magnetic field. (For examples, see the “Other Environmental Hazards” section of the Physician’s Manual.) If a pulse generator ceases operation while in the presence of electromagnetic interference (EMI), moving away from the source may allow it to return to its normal mode of operation. VNS Therapy System operation should always be checked by performing device diagnostics after any of the procedures mentioned in the Physician’s Manual.

For clear imaging, patients may need to be specially positioned for mammography procedures, because of the location of the Pulse Generator in the chest. (Most routine diagnostic procedures, such as fluoroscopy and x-radiography, are not expected to affect system operation.)

Therapeutic radiation may damage the pulse generator’s circuitry, although no testing has been done to date and no definite information on radiation effects is available. Sources of such radiation include therapeutic radiation, cobalt machines and linear accelerators. The radiation effect is cumulative, with the total dosage determining the extent of damage. The effects of exposure to such radiation can range from a temporary disturbance to permanent damage, and may not be detectable immediately.

External defibrillation may damage the pulse generator. Please refer to the Physician’s Manual for complete instructions for external defibrillation.

Use of electro surgery (electrocautery or radio frequency (RF) ablation devices) may damage the pulse generator. Please refer to the Physician’s Manual for complete instructions for use during electro surgery.

Magnetic resonance imaging (MRI) should not be performed with a magnetic resonance body coil in the transmit mode. The heat induced in the bipolar lead by an MRI body scan can cause injury. If an MRI should be done, use only a transmit and receive type of head coil. MRI compatibility was demonstrated using a 1.5T General Electric Sigma Imager. When other MRI systems are used, adverse events may occur because of different magnetic field distributions.

No scan in which the radiofrequency (RF) is transmitted by the body coil should be done on a patient who has the VNS Therapy System. Thus, protocols must not be used which utilise local coils that are RF-receive only, with RF-transmit performed by the body coil. Note that some RF head coils are receive only, and that most other local coils, such as knee and spinal coils, are also RF-receive only. These coils must not be used in patients with the VNS Therapy System.

Therapeutic ultrasound. Routine therapeutic ultrasound could damage the pulse generator and may be inadvertently concentrated by the device, causing harm to the patient.

Extracorporeal shockwave lithotripsy may damage the pulse generator. If therapeutic ultrasound therapy is required, avoid positioning the pulse generator part of the body in the water bath or in any other position that would expose it to ultrasound therapy. If that positioning cannot be avoided, programme the pulse generator output to 0 mA for the treatment, and then after therapy, reprogramme the pulse generator to the original parameters.

Diagnostic ultrasound is not expected to affect the VNS Therapy System.

The pulse generator may affect the operation of other implanted devices, such as cardiac pacemakers and implantable defibrillators. Possible effects include sensing problems and inappropriate pulse generator responses. If the pulse generator patient requires concurrent implantable pacemaker and/or defibrillator therapy, careful programming of each system is necessary to optimise the patient’s benefit from each device.
 

 

Adverse Events

 

Adverse events reported during clinical studies as statistically significant are listed in alphabetical order: Ataxia (muscle movements or twitching, generally associated with stimulation); Dyspepsia (indigestion); Dyspnea (difficulty breathing, shortness of breath); Hypesthesia (impaired sense of touch); Increased coughing; Infection; Insomnia (inability to sleep); Laryngismus (throat, larynx spasms); Nausea; Pain; Paresthesia (prickling of the skin); Pharyngitis (inflammation of the pharynx, throat); Voice alteration (hoarseness); Vomiting.

Other potential adverse events possibly associated with surgery or stimulation include but are not limited to the following: Aspiration (fluid in the lungs); Blood clotting; Choking sensation; Damage to nerves or vasculature in the surgical area, including the carotid artery and jugular vein; Device (Generator and/or Lead) migration or extrusion; Dizziness; Dysphagia (difficulty swallowing); Duodenal ulcer, gastric ulcer; Ear pain; Facial flushing; Facial paralysis, paresis; Foreign body reaction to implants, including possible tumour formation; Formation of fibrous tissue, pockets of fluid; Heart rate and rhythm changes; Hiccupping; Incision site pain; Irritability; Laryngeal irritation (sore, painful throat); Left hemidiaphragm paralysis; Left recurrent laryngeal nerve injury; Left vocal cord paralysis; Low-grade fever; Muscle pain; Neck pain; Nerve injury; Painful or irregular stimulation; Skin, tissue reaction; Stomach discomfort; Tinnitus (ringing in the ears); Tooth pain; Unusual scarring at the incision site; Urinary retention; Vagus nerve paralysis; Weight change; Worsening of asthma and bronchitis; Worsening of cardiac abnormalities, including heart rate and rhythm.

Patients who manipulate the pulse generator and bipolar lead through the skin may damage or disconnect the bipolar lead from the pulse generator and/or possibly cause damage to the vagus nerve.
 

 

Pre-Clinical Study, Teratogenic Effects

 

There are no adequate and well-controlled studies of VNS Therapy in pregnant women. Reproduction studies have been performed using female rabbits stimulated with the commercially available VNS Therapy System at stimulation dose settings similar to those used for humans. These animal studies have revealed no evidence of impaired fertility or harm to the foetus due to VNS Therapy. Because animal reproduction studies are not always predictive of human response and animal studies cannot address developmental abnormalities, VNS should be used during pregnancy only if clearly needed. Although the operating ranges of the VNS Therapy System and foetal monitors are dissimilar and no interaction would be expected, testing has not been performed. Therefore, the potential may exist for interaction between the VNS Therapy System and foetal monitoring systems.