Akella Chendrasekhar, MD, FACS

• Medical Director, Trauma
• Medical Director, Emergency Department
• Wyckoff Heights Medical Center
• Brooklyn, New York

There have been recent advances in biventricular pacing beyond standard unipolar and bipolar configurations weak erectile dysfunction treatment generic 100 mg kamagra polo with mastercard, though these require the use of unique leads and generators female erectile dysfunction drugs order 100mg kamagra polo amex. The addition of several poles that can act as the cathode along the body of the lead allows the identification of areas more proximally along the cardiac venous system where phrenic capture may be avoided or where placing a bipolar lead may be difficult due to issues with stability erectile dysfunction treatment in delhi purchase generic kamagra polo pills. For example impotence blood circulation cheap 100mg kamagra polo with mastercard, the tip of a quadripolar lead may be fixed in a distal position in a cardiac vein for stability erectile dysfunction doctors in san fernando valley order kamagra polo us, but a more proximal electrode may be used for pacing if local threshold or phrenic nerve capture may be limiting in other positions diabetic erectile dysfunction icd 9 code purchase kamagra polo with visa. In addition, only one device manufacturer currently provides the lead and currently it cannot be used with generators made by other manufacturers. The pulse generator is made up of the connector block (header) and device enclosure. They have become increasingly complex, while at the same time becoming smaller and more reliable, without compromising longevity. It is not possible for the clinician to be familiar with every design aspect of each pacing system. Device encyclopedias are published by all manufacturers and contain detailed specifications for pulse generators and leads. Furthermore, a product manual is available for each device and contains an even more comprehensive description of the device specifications and function. It is necessary for the clinician to have a fundamental knowledge of pacemaker design and function in order to select the appropriate hardware for a given patient and to evaluate new products as they are introduced. Lead designs, materials, and functional characteristics Pacing leads have five major components: electrodes, conductors, insulation, connector pin, and fixation mechanism. The design and functional characteristics of these components will be discussed together. With respect to these five components, the basic endocardial pacing lead has not undergone significant change in the last decade. There is also a lack of sufficient clinical data to recommend routine clinical use of this modality at this time. The tip of the lead is the cathode and the pacemaker generator completes the circuit as the anode. Thus, pacing and sensing are accomplished as a bipolar circuit, but the lead is referred to as unipolar because only one electrode is in contact with the heart. Due to their relatively simple design, endocardial unipolar leads have demonstrated impressive longevity and many are still in service today. With a bipolar pacing lead, the pulse generator is not part of the pace/sense circuit. Both the ring electrode (anode) and the tip electrode (cathode) are in contact with the myocardium. In a co-axial design, the inner conductor is arranged in a coil that extends to the tip of the lead (cathode) and has a central lumen to allow passage of a positioning stylet. A layer of insulation then covers the inner coil, electrically separating it from the outer coil that extends to the ring electrode. These leads can be attached to the endocardium via an active or passive fixation tip. The filar count of the inner and outer coils can be variable, depending on the goals of the manufacturer. The co-axial, four-layer design is an industry standard for most pacing leads, but this limits the minimum achievable lead diameter. The coils are then covered with an outer layer of insulation, usually polyurethane. The electrical performance and reliability of current leads using a co-radial design is comparable to those using a co-axial design. In this design, a central coil conductor extends to the tip, allowing for stylet or guidewire insertion. Conductors for the more proximal electrodes are cables arranged in parallel that terminate at their respective electrodes. Since multiple pacing vectors are available, it may be possible to overcome phrenic nerve stimulation, pace from electrically more advantageous sites, or pace from sites with better pacing thresholds. Fixation mechanisms the chronic performance of permanent pacing leads is critically dependent on stable positioning of the electrode(s). Passive fixation leads have tines (fins) near their tip, which are made of the same material as the insulation. Effective fixation of the lead can be confirmed at the time of implantation by its gentle traction or rotation. The passive fixation leads are rapidly covered by fibrous tissue, making removal of the lead by simple traction difficult or impossible in as short a time as 6 months. In general, passive fixation leads are more difficult to extract than active fixation leads. Despite the overall low rates of dislodgement, passive fixation leads are not suitable for every patient. This fact is important to understand when attempting to electrically "map" the myocardium for suitable implant sites. In leads with a fixed helix design, the helix is coated with mannitol or polyethylene to facilitate introduction of the lead through the vasculature into the desired chamber. The coating dissolves within a few minutes, allowing the lead to be positioned with a stylet. Fixation is performed by rotation of the entire lead body and transmission of the torque to the distal tip. These leads have similar electrical performance characteristics to other designs with comparable rates of dislodgement. Active fixation leads allow for stable positioning of the lead at many sites in either the atrium or the ventricle. Although active fixation leads are easier to extract than passive fixation leads, the risk of myocardial perforation during and after implantation is higher. Historically, the chronic pacing thresholds of active fixation leads were higher than those of passive fixation leads. This difference has largely been eliminated with the routine use of corticosteroids in active fixation leads. Most active fixation leads are straight and can be implanted in either the atrium or ventricle with the use of preformed or user-shaped stylets. Confirming adequate fixation is also important for acute stability and long-term lead function. Fixation to the myocardium causes injury to the tissue, known as the current of injury (see "Current of injury"). In addition, the morphology of the current of injury and time course of resolution have been studied. There is inadequate data to comment on the morphology, but rapid resolution of the current of injury may be associated with inadequate fixation. The current of injury should be used in conjunction with other measured parameters (including slew rate, signal amplitude, pacing impedances, and thresholds) to guide implantation of leads. Finally, the implanter should be familiar with the fluoroscopic appearance of the lead tip with the helix extended. The implanter has to balance the frequently competing objectives of lead stability, electrical performance, avoidance of phrenic nerve capture, and resynchronization performance. Familiarity with a range of sizes, shapes, and fixation mechanisms of available leads is necessary for successful implantation. Another factor to consider is that some leads do not have isodiametric lead bodies. The tip diameter may then be the limiting factor when matching the lead to the anatomical target vessel. Some leads (Boston Scientific Easy Trak2) are straight with tines that allow them to be wedged into a distal target vessel and help provide additional stability through frictional force. Other leads have multiple cants or curves that apply pressure to the vessel wall, again providing stability by frictional force. Alternatives to canted leads are leads with sigmoidal biasing in two dimensions (S shaped) or helical biasing in three dimensions (spiral). These leads also rely on the friction created both from wedging the distal tip in a branch and from the multiple contact points on the vessel walls. If a distal branch cannot be engaged or is prohibited due to phrenic nerve or extracardiac stimulation, a proximal position can be targeted with a lead such as the Medtronic Attain 4195 StarFix lead. Epimyocardial leads Permanent epicardial pacing leads are used when tricuspid valve abnormalities, central venous obstruction, congenital heart disease, or technical issues preclude transvenous lead placement. Epicardial leads may also be used when recurrent bloodstream infection is a concern, or when there is a need for lead implantation co-incident with another intrathoracic surgical procedure. Fixation mechanisms include a fishhook-shaped electrode that is stabbed into the atrial myocardium or a large screw helix that is rotated into the ventricular myocardium. These leads are typically unipolar and are frequently non-steroid eluting, with chronic stimulation thresholds that are higher than those of modern endocardial electrodes. This lead design, which is available in unipolar and bipolar models, has the advantage of lower chronic pacing thresholds and better long-term performance. It may require greater cardiac exposure and can be technically more difficult to place. The presence of regions of epicardial fat can limit effective implant locations for all epicardial leads. Because epicardial leads have a higher rate of developing unacceptably high pacing thresholds, it is the practice of some cardiothoracic surgeons to implant two leads in a given cardiac chamber, with the second lead either connected to a different pacemaker port or left capped in the pacemaker pocket. The materials used in the construction of these leads and lead components are manufactured to very high industrial standards. Although the materials used by each manufacturer are similar, there are significant differences in how these materials are applied and in the construction of the leads. Some materials, such as co-polymer insulations, are unique to a specific manufacturer. It is characterized by biocompatibility, high tensile strength, and resistance to corrosion. The resulting wire combines increased fatigue life, high conductivity, and solderability with the ability to withstand greater mechanical stresses. Extreme compressive forces are applied in order to form a sound mechanical bond between surfaces. The tensile strength and electrical resistivity of this wire depend on the amount of silver in the core, which can be manufactured to the needs of the lead engineers. The number of wires used in a cable is related to its intended use, with larger cables used for high voltage applications and smaller cables for pacing applications. Cable conductors offer greater strength, fracture resistance, and redundancy than coiled conductors. The number of filaments and their arrangement within a given cable is variable from manufacturer to manufacturer, even for similar applications. Fractures due to fatigue cracking appear uncommon and usually occur at points of high mechanical stress, such as at the anchoring sleeve or costoclavicular ligament. These characteristics are important because they affect the flexibility of the coil as well as its resistance to fracture. Wire diameter, number of filars (wires), and pitch all vary between manufactures and between lead families of a given manufacturer. Multifilar coils offer lower electrical resistance (optimal), but may have lower fatigue life when compared to bifilar designs. Insulation the materials used in pacemaker leads for insulation play a critical role in their longevity and reliability, as well as in handling and implant characteristics. There is no single ideal insulation and some leads are constructed using multiple materials. Fluoropolymers are fluorocarbon-based polymers that are characterized by high resistance to solvents, acids, and bases. Therefore, they have maximum biocompatibility and tensile strength, but their stiffness limits their use to thin coating (<0. Conductors are coated with a fluoropolymer layer to prevent adverse interactions with silicone tubing. It also has high resistance to extreme temperatures and therefore is less susceptible to damage from electrocautery. Its main disadvantage is its low tensile strength, making it prone to tearing and abrasion wear. Abrasion wear comes from lead-to-can and leadto-lead interaction within the pocket. Silicone also has a high co-efficient of friction, making it difficult to pass alongside other leads. When silicone is used as primary insulation, relatively thick layers are used and covered with a lubricious coating or polyurethane in order to improve handling characteristics. Of the insulation materials in use today, polyurethanes have the lowest biostability, relatively speaking.

It is used for the treatment of infertility in women who have anovulatory menstrual cycles osbon erectile dysfunction pump buy kamagra polo 100 mg amex. Potential risks of the use of clomiphene include the stimulation of multiple follicles and release of multiple eggs impotence treatments generic 100mg kamagra polo amex, with a resultant multiple gestations erectile dysfunction causes psychological trusted kamagra polo 100 mg. The antiestrogen effect may precipitate hot flashes and abnormal uterine bleeding erectile dysfunction causes cures cheap kamagra polo 100mg with amex. Understand the structures impotence organic buy kamagra polo now, mechanism of action erectile dysfunction and pregnancy purchase kamagra polo online, and effects of natural gonadal hormones. Know the therapeutic uses and adverse effects of estrogens, progestins, and androgens. Describe the drugs used as antiestrogens, antiprogestins, and antiandrogens, their therapeutic uses, mechanisms of action, and adverse effects. A group of drugs that display tissuespecific estrogen agonist or antagonist activity. Antagonists acting within the system also have uses in treating hormone-dependent cancers and as abortifacients. The menstrual cycle is controlled by a complex feedback system between the hypothalamus, pituitary, and ovaries (see Case 39). This change in pituitary responsiveness requires levels of serum estradiol above 150 pg/mL for 36 hours. After ovulation, the corpus luteum is able to secrete progesterone for its lifetime of 14 days if pregnancy does not occur. A frequent cause of infertility is a disruption in the complex feedback regulatory patterns that results in anovulation. The ovary produces a number of estrogens; the most important are 17a-estradiol and estrone. The precise role that each of these receptors plays in mediating the various effects of the estrogens is unclear. On binding an estrogen, a conformational change occurs in the receptor such that additional proteins are recruited to the receptor. These proteins, called coactivators, are able to increase the transcription rate of estrogen-dependent target genes. These two isoforms are derived from a single gene by differential use of two promoters within the progesterone receptor gene. Thus, the amplitude of the effects elicited by progesterone depends on the ratio of the two isoforms. Oral Contraceptives Oral combination contraceptives contain synthetic estrogens, most commonly ethinyl estradiol, and a progestin (for example, norethindrone or norgestrel). Over the past several years the doses of estrogen in combination oral contraceptives have diminished, and the ratio of estrogen to progestin has evolved from a fixed ratio (monophasic) to biphasic and triphasic regimens with varying ratios that attempt to more closely mimic the ratio during the normal menstrual cycle. The primary mechanism of action of oral contraceptives is prevention of ovulation. Oral contraceptives also alter transport of the ovum down the fallopian tube; increase the viscosity of mucus produced by the cervix, which impairs sperm entry; and create an endometrial environment less favorable to implantation. Several preparations are available for continuous dosing for 84 or 365 days; this reduces the number of bleeding periods per year. Progestin-only contraceptives may be administered as a daily oral dose, a depot injection (medroxyprogesterone acetate), or as a progestin (L-norgestrel) implant. Their effectiveness approaches combination oral contraceptives, and both the depot injection and the implants have the advantage of a long duration of action (14 weeks for the injection, 5 years for the implants). Progestins alone inhibit ovulation approximately 70 percent of the time, but their effectiveness is increased by effects on the endometrium and cervical mucus production. Several emergency ("morning-after") contraceptive regimens have been used effectively to prevent pregnancy if used within 72 hours of coitus. Alternative (Plan B) schedule includes 2 doses of 750 mcg of L-norgestrel over 1 day; Plan B One Step is one 1. Hormone Replacement Therapy the decline in the production of estrogens that occurs at and following menopause is associated with increased rates of bone loss that can result in frank osteoporosis, vasomotor symptoms such as hot flashes and night sweats, vaginal dryness and thinning, and genital atrophy. All of these symptoms can be alleviated by estrogens, but careful assessment of the risk-benefit ratio for a given patient is essential. The most commonly prescribed oral estrogen preparation for postmenopausal therapy is a complex mixture of natural estrogens (conjugated equine estrogen, Premarin), by mass mostly estrone sulphate and equilin estrogens, and this is usually combined with medroxyprogesterone acetate to avoid unopposed estrogenic stimulation of the endometrium. Other Uses of Estrogens and Progestins Estrogens can be used to treat circumstances of inadequate hormone production as in primary hypogonadism. Estrogens are also useful in the treatment of intractable dysmenorrhea where inhibition of ovulation may be of therapeutic value. Relatively high doses of estrogens have been used to suppress ovarian production of androgens. Both of these therapeutic approaches depend on estrogen-mediated negative feedback inhibition of gonadotropin release. Estrogen/progesterone combinations as in oral contraceptives can also be used to reduce acne, to regulate menstrual cycles, to diminish menstrual flow, and for preventing or improving menstrual migraines. Adverse Effects of Estrogens and Progestins Most of the adverse effects associated with estrogens and progestins are extensions of their physiologic actions. Uterine bleeding is the most common adverse effect associated with use of estradiol. The increased risk of cancer caused by estrogen and progesterone use remains a significant concern. Unopposed estrogen treatment has been well documented to cause an approximate threefold increase in the risk of endometrial cancer. Addition of a progestin to a treatment regimen essentially eliminates this increased risk. Several very large clinical trials examining use of estrogens to treat postmenopausal women have indicated that there is an increased risk of breast cancer with estrogen plus progesterone treatment, and further studies suggest that it is the progestin that is likely responsible for this effect. These studies do also show that estrogens decrease the risk of endometrial, ovarian, and colon cancer. Estrogens do increase the risk of stroke; the underlying mechanism for this increased risk is unclear, but may involve the increased coagulability that is associated with estrogen treatment. This mechanism may also participate in the increased risk of dementia in postmenopausal women treated with estrogens. It must be noted that these serious adverse effects have been documented only with Premarin or Premarin plus progesterone at a fixed dosage, and it is not certain if other dosing regimens or other estrogen preparations cause similar untoward effects. Less serious adverse effects of estrogens include nausea and vomiting and peripheral edema. Clomiphene is a partial agonist that consists of two isomers, cis-clomiphene and trans-clomiphene. Cis-clomiphene is a weak estrogen agonist, whereas trans-clomiphene is a potent estrogen antagonist. The major pharmacologic action of clomiphene is to block estrogenmediated negative feedback in the pituitary. It does increase the number of ova released, thereby increasing the chances of twinning. Adverse effects of the antiestrogens include hot flashes, ovarian enlargement, and nausea. For example, tamoxifen is an estrogen receptor antagonist in the breast but is a weak estrogen agonist in the endometrium. The basis for this tissue specificity is a combination of drug-induced conformational changes in the receptor, and the complement of coactivators expressed in a given cell type. If the cell does express a coactivator that recognizes a particular configuration, then the drug will have agonist (or partial agonist) activity. It acts as an estrogen antagonist in the breast and in the brain, but it has weak estrogen agonist activity in the uterus and in bone. Tamoxifen has been shown consistently to increase disease-free survival and overall survival; treatment for 5 years has reduced cancer recurrence by approximately 50 percent and death by nearly 30 percent. It is approved for primary prevention of breast cancer in women at high risk, where it causes a 50 percent decrease in the incidence of invasive breast cancer and a 50 percent reduction of noninvasive breast cancer. Because of the development of drug-resistant tumors, treatment should last for no more than 5 years. Raloxifene is a polyhydroxylated nonsteroidal compound with a benzothiophene core. Raloxifene is an estrogen agonist in bone, where it exerts an antiresorptive effect. Adverse effects include hot flashes, deep vein thrombosis, and cramps in the lower extremities. These agents act by reducing the peripheral conversion of precursors such as androstenedione and testosterone into estrogens. They significantly suppress serum estradiol levels and offer an alternative to tamoxifen in postmenopausal women with receptorpositive breast cancer. A single oral dose of mifepristone combined with a vaginal suppository containing prostaglandin E1 is effective in terminating pregnancy in approximately 95 percent of cases if used in the first 7 weeks of gestation. Androgens and Antiandrogens Testosterone produced by the testes is the major androgen in humans. In many peripheral tissues, testosterone is converted to dihydrotestosterone by the enzyme 5-reductase. As an anabolic agent it promotes linear bone growth and development of internal genitalia, and increases muscle mass. As an androgenic agent, it is responsible for the development of male secondary sexual characteristics. There are two distinct chemical classes of androgens: testosterone and its esters and the 17-alkyl androgens. Testosterone esters include testosterone enanthate, testosterone cypionate, and testosterone undecanoate. The 17-alkyl androgens include methyltestosterone, oxandrolone, danazol, and stanozolol. Testosterone and its esters are administered either as depot injections via transdermal patch or as a gel. The major use of the androgens is the treatment of male hypogonadism, both in adults and in prepubertal boys who produce low amounts of testosterone. Use in adults has been reported to increase libido, reduce senescence, and reduce the rate of bone resorption. The major adverse effects of testosterone and its esters are caused by the androgenic actions, which are especially apparent in women and prepubertal children. In women, these adverse effects include hirsutism, acne, amenorrhea, and a thickening of the vocal chords. In men, androgens can produce azoospermia, decreased testicle size, and prostatic hyperplasia. The major adverse effects of the 17-alkyl androgens include masculinization and also serious hepatotoxicity. Antiandrogens Abnormal growth of the prostate is usually dependent on androgenic stimulation. This hormonal stimulation can be reduced by orchidectomy or high doses of estrogens, but either of these treatments may be undesirable. In clinical trials, finasteride decreased the incidence of prostate cancers but may have led to more aggressive tumors. It is effective in the treatment of metastatic castrate-resistant prostate cancer. She asks why she is having vaginal bleeding if the medication blocks estrogen effect in the body. It has estrogen agonist effect of the breast and uterus, thereby leading to endometrial hyperplasia. It is an estrogen antagonist in the breast and uterus, leading to loss of endometrial cells. It has no effect on the uterus, and the vaginal bleeding is caused by something else. Tamoxifen has an estrogen antagonist effect on the breast but a weak agonist effect on the uterus, leading to endometrial hyperplasia in some women. Antiandrogens are used to treat androgen-dependent cancers such as prostate carcinoma. Aromatase inhibitors in the treatment of recurrent ovarian granulosa cell tumors: brief report and review of the literature. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. He has noticed a 20-lb weight gain in the past few months without any change in his diet or activity level. On examination, his blood pressure is elevated at 165/95 mm Hg, but his other vital signs are normal. His face is plethoric, and he has a small fatty hump developing on his upper back. Skin examination is notable for moderate facial acne and multiple violaceous striae on the abdomen. Blood tests show an elevated glucose level of 150 mg/dL, normal electrolytes, and renal function. You suspect idiopathic Cushing disease and order a dexamethasone suppression test to assist with confirming the diagnosis. Their effects are mediated by specific intracellular glucocorticoid receptors that modulate the transcription rates of specific genes and results in increases or decreases of specific proteins.

Diagnosis of pacemaker lead infection necessitates the removal of all pacing hardware after antibiotics have been started erectile dysfunction ed treatment buy kamagra polo 100 mg online. This problem may also first appear after implantation and can sometimes be corrected with reprogramming treatment erectile dysfunction faqs purchase 100mg kamagra polo mastercard, although lead revision may be required what is erectile dysfunction wiki answers generic kamagra polo 100mg with amex. Newer lead design erectile dysfunction type of doctor cheap kamagra polo 100mg, such as the quadripolar lead configuration impotence thesaurus buy kamagra polo 100mg low cost, may reduce the risk of this problem and allow for more options for "electronic repositioning erectile dysfunction groups in mi order discount kamagra polo on line. The ease of accomplishing lead removal and the associated risks are related to the time the lead has been implanted. The concept of "lead management" has come into vogue; it implies limiting the number of intravascular leads to those actively providing a service to the patient and removing non-functional or potentially problematic leads at an earlier time such that the process is easier, and perhaps, complications such as venous occlusion and device system infection are reduced. When we speak of lead extraction, we are generally concerned with the special challenges presented by a chronically implanted lead. The Complications of biventricular pacing Implantation of a coronary venous lead is the major procedural difference between biventricular and simple dual chamber pacemakers. The technical challenge of this procedure has decreased with improvement in lead design and delivery equipment. Coronary sinus perforation may lead to pericardial tamponade requiring urgent drainage. With better leads and delivery equipment, and greater operator experience, lead placement has been facilitated and the procedure times as well as the significant complication rate reduced. These definitions have some importance in terms of the requisite qualifications of physicians performing the respective procedures (see "Techniques"). There are two general approaches for the removal of pacing leads: percutaneous and transthoracic. Most pacing physicians and surgeons believe that if extraction is to be performed it should be done percutaneously. Certainly, simple traction on the lead is easy, straightforward, and logistically undemanding. If all leads would yield to this treatment there would be little debate as to the threshold for lead extraction and even less support for the more invasive surgical option. Unfortunately, chronic leads are not so readily removed and, even with the variety of tools available to assist in the percutaneous technique, the procedures may be long, difficult, and associated with a finite mortality and significant morbidity. The risks of lead removal correctly influence the aggressiveness with which one should pursue this approach. Post-mortem pathological studies of the hearts of patients with permanent pacemakers have revealed intense fibrosis and encapsulation, especially involving the ventricular portion of the lead, and including the tricuspid valve and its supporting apparatus. Attempts to remove these leads ex vivo are associated with myocardial avulsion, valve damage, and disruption of the lead. Implants of longer duration tend to have more extensive fibrosis, but significant encapsulation of an atrial lead has been observed at post-mortem examination 6 weeks after implantation. Contemporary leads are of low profile and primarily co-axial bipolar in configuration; they do not, in general, tolerate the physical forces that may be necessary to extract them by simple traction in the presence of significant fibrosis. Over the last decade powered sheaths (laser, electro-dissection, and mechanical/ rotational) have been shown to facilitate lead extraction and increase the overall success rate. The specific events that might complicate lead extraction pertain to the physical forces used to strip away fibrous adhesions to the lead body, and those used to extricate the tip of the lead from the heart. Catastrophic events, when they occur, usually result from either a laceration of a central vein by an extraction tool or perforation of the heart at the site of tip fixation. Embolization of a very large vegetation or thrombus to the pulmonary artery may also cause death. Damage to the tricuspid valve, or embolization of a lead fragment or thrombus to the lung, or through a patent foramen ovale to the systemic circulation, may also occur. Although most complications become evident during or shortly after the extraction procedure, some, such as a hemothorax, pulmonary embolism, or pericardial tamponade, may be delayed in presentation. Because of the risks involved it is essential that adequate informed consent be obtained from the patient and that the reasons for performing lead extraction, the potential risks and benefits, and alternatives are thoroughly discussed with the patient and family by the operator. Indications Lead extraction has inherent risks; thus the decision to undertake the procedure must be weighed against the risk of not extracting the lead. This classification primarily addresses the nature of the risk to the patient of not removing a lead, but it does not approach the risk of extracting a chronically implanted lead in a specific patient. Thus, an infected lead is often surprisingly easy to remove, whereas elective removal of a non-functioning passive fixation lead that has been in place for a number of years may be extremely difficult and result in complications. A number of modifying factors based on clinical parameters thought to influence the risk of lead extraction have been included in the indication guidelines for the extracting physician to consider. These factors are not absolutes, but rather provide a context in which to assess the risks for each specific situation and weigh these against the perceived benefit of extraction. An infected lead provides the strongest indication for lead removal, since complete removal of all prosthetic material has been shown to be necessary for eradication of the infection in most cases. Of the remaining six patents, three (50%) had relapse of infection, whereas only one of the 117 successfully extracted patients had relapse, and this single relapse resulted from reuse of an infected pocket. In addition, 10% of cases were polymicrobial and in 12% no organism could be identified. Retained non-infected but non-functioning hardware generally poses little immediate risk to the patient, but may complicate the placement of additional pacing leads either by adding to the venous obstruction (and the risk of thrombosis/ embolization) or by generation of spurious electrical potentials between leads. Since complications of extraction increase with time elapsed since lead implantation, some argue for routine extraction, rather than abandonment, of unused leads in these patients. There are leads, however, that may exhibit normal electrical function but offer a physical risk to the patient. The Accufix J lead presents a unique risk to the patient in that a small metal wire placed within the lead for the purpose of maintaining the J shape is subject to fracture under the stress and strain of repetitive cardiac motion. The fractured wire may Totalminorcomplications Anycomplication wear through the insulation and perforate the heart, causing cardiac tamponade or mediastinal hemorrhage. Complete mitigation of this risk when the lead was recalled in 1994 would have required lead extraction in the approximately 45 000 implanted patients. However, a registry established to study this issue concluded that the risk of death from elective lead extraction of non-fractured leads is higher than the risk of injury from the lead itself. Of the 13 patients who died in this registry, five died from pericardial tamponade, three from hemothorax, one from pulmonary embolus, and one from innominate arteriovenous fistula. In centers with higher procedure volumes, clinical success rates were higher and major adverse event rates were lower. Increasing operator experience appears to reduce the risk of complications, and some highly experienced operators have reported complication rates lower than those reported in multicenter series. Risk of a major complication was associated with female gender, number of leads in place, and implant duration, whereas risk of any complication was related to less experienced operators (<50 procedures). Extraction of any chronically implanted lead should be undertaken only after careful consideration of the risk-to-benefit ratio, including patient age, overall health, presence of calcification or vegetations involving the leads, duration of implant, and patient preference to assume additional risk. In addition to the acute risks of lead extraction, physicians should be aware of the potential for late mortality after the procedure; between 15% and 25% at 1 year in some series in which extraction was performed for infection. Technique Extraction of chronically implanted endocardial leads should be undertaken only by experienced physicians and surgeons skilled in the required techniques. Unfortunately, this procedure is not frequently performed and there are few opportunities even in fellowship programs to receive adequate formal training. Acknowledging the well-documented association between complications and inexperienced operators, guidelines for the qualification of physicians have been proposed. A chest radiograph should be performed to exclude the presence of undocumented hardware. It is necessary to know if complete removal of all leads is essential and whether a new device will be implanted as part of the same procedure. Lead extraction may be performed in either a specialized electrophysiology laboratory or in a cardiac surgical operating room. Regardless of the venue, equipment, and personnel needed to perform emergency thoracotomy and cardiopulmonary bypass should be immediately available. Anesthesia personnel should be available to provide deep sedation or general anesthesia. We almost always use an assistant for these procedures (either a fellow or second attending physician) due to the amount of equipment that must be controlled during the case, as well as to increase exposure to these procedures. The routine preparation for lead extractions involves one or both groin areas for the placement of a venous line (6-Fr sheath) in the right femoral vein and a small arterial line in a femoral or radial artery for continuous monitoring of the arterial blood pressure. The femoral sheath provides for rapid fluid administration, emergent passage of a temporary pacing wire, and ability to upgrade to a femoral approach to extraction should such be needed. The chest, abdomen, and femoral regions are prepared with chlorhexidine- or iodine-based antiseptic solutions such that emergent thoracotomy could be performed. Drapes are liberally placed so that a sterile field is maintained from the neck to the thighs. If the patient is pacemaker dependent, a temporary pacing wire is inserted through either a femoral or an internal jugular vein. If prolonged temporary pacing will be needed, we employ a "permanent" active fixation lead as the temporary device via the contralateral internal jugular vein for added security against lead dislodgement during the interim period. All of our extractions are performed with a transesophageal echo probe available and after interrogation of the heart, valves, pericardial space, and leads has been performed. A commercially available lead-extraction kit supplemented by a variety of other tools (such as snares, wires, locking stylets, biopsy forceps, guidewires, and laser extraction sheaths) should be available. The operator should have on hand all of the tools that may be needed in a complex case, whether their use is anticipated or not. All the equipment necessary for emergent heart surgery (including cardiopulmonary bypass) should be available. The extraction procedure cannot start unless a designated surgeon is confirmed to be available for emergent assistance if such is needed. The operator should have in mind a step-by-step approach to the specific problems presented by the case, and be ready to respond to emergencies as they arise. The pocket is usually entered through the previous incision line, although this may be altered to include a site of erosion or skin necrosis. With a combination of sharp and blunt dissection, the generator and leads are freed. Electrocautery is essential in freeing leads that are often extensively fibrosed to themselves and subcutaneous tissue. The lead is traced to the venous entry point, the suture sleeve is identified, and all retention sutures are cut and removed. The lead is disconnected from the generator and its internal integrity is accessed by passing a standard stylet to the tip. In most cases, an initial attempt at gentle traction is worthwhile, but care must be taken not to damage the lead during this process. Observation during gentle traction also gives an idea about possible sites of lead attachment to the surrounding tissue. For active fixation leads, the helix should be retracted in order to facilitate removal and reduce the risk of cardiac perforation. If the retraction mechanism is not effective (or if this is a non-retractable helix), an attempt should be made to rotate the entire lead counter-clockwise to unscrew the tip from the heart. This may be impossible in situations where the body of the lead is extensively fibrosed to the heart and veins. While extraction of an active fixation ventricular lead with the helix extended is not likely to be a problem, an atrial lead may come free with a small full thickness piece of the wall, resulting in pericardial bleeding and potential tamponade. Tools for extraction A variety of tools are available to assist with lead extraction. A partial list of equipment which should be available to the operator is given in Table 5. Techniques for lead extraction can be broadly categorized into the superior approach (utilizing a locking stylet and telescoping sheaths placed over the lead to provide traction and countertraction) and the femoral approach (using different types of grasping snares and wires to remove leads). The central lumen of the lead is identified and carefully dilated with a coil-expander tool. The diameter of the lumen is then determined by the insertion of a series of gauge pins. A locking stylet of a size corresponding to the largest gauge pin accepted by the lead is then advanced through the lumen to the lead tip. This device is essential to focus the force of traction as close to the lead tip as possible, and to distribute traction along the length of the lead. Because current generations of these devices have a greater flexibility in adapting to a range of inner core diameters, fewer different types and sizes need to be stocked. The operator needs to be familiar with the specific directions for each of the locking stylets he/she uses. It may be difficult or impossible to reverse the locking mechanism and remove these devices once they are inserted into the lead. Some manufacturers incorporate "cables" into the insulation of the defibrillator leads to provide additional traction during lead extraction. In patients with inner conductor failure, the inner lumen of the lead may be interrupted, making it impossible to pass a locking stylet. Most of these sheaths are provided with a shorter "outer" sheath that can be advanced co-axially in a telescoping fashion to aid in the extraction process. In many cases, applying considerable countertraction and torque to the sheath is necessary to separate the lead from fibrous adhesions. Traction upon the lead via the locking stylet (usually maintained by the assistant) facilitates the processes. Correct positioning of the sheath provides a mechanism for countertraction to be applied to the lead tip to facilitate extraction.

Because lithium requires serum levels and perhaps a bit more diligence in its initial management compared with other treatments (namely antipsychotics) erectile dysfunction drugs boots order kamagra polo 100 mg without a prescription, it is now often disregarded in short-term erectile dysfunction diabetes pathophysiology kamagra polo 100 mg generic, acute inpatient settings; this disregard is unfortunate erectile dysfunction treatment natural in india cheap kamagra polo 100 mg fast delivery, as lithium remains a first-line treatment for bipolar disorder (the author believes it is the first-line treatment); for many people erectile dysfunction treatment psychological generic kamagra polo 100 mg otc, it is the most effective intervention erectile dysfunction in diabetic subjects in italy cheap kamagra polo 100mg mastercard. Although there are loading dose strategies that have been developed to predict the best "final" dose for lithium erectile dysfunction drugs in nigeria order genuine kamagra polo line, these are rarely used because of toxicity concerns. Nonetheless, with experience, clinicians can learn to balance the pressures of short inpatient stays with the initial challenges of starting lithium. Perhaps the limiting factor for using lithium is the risk of toxicity and side effects. Symptoms of toxicity include slurred speech, disorientation, ataxia, tremors, muscle twitches, cardiac arrhythmias, and nystagmus that can progress to coma and even death. Any significant acute lithium toxicity is a medical emergency requiring immediate attention that includes discontinuing lithium treatment, hydration, and aggressive supportive care. Nearly always, these symptoms resolve once the serum level returns to the therapeutic range. Gastrointestinal side effects are most common, but will often resolve over time; short-release formulations are more likely to cause nausea, whereas delayed-release preparations are more likely to cause diarrhea. Lithium is not typically sedating but does sometimes produce cognitive dulling that may not be tolerated; the latter may improve on lower serum levels. A mild tremor is common even on therapeutic doses (and sometimes a way to determine if someone is taking lithium even in the absence of a serum blood level). Restricting water intake for the couple of hours before bedtime might help with nighttime awakening to go to the bathroom. Some studies suggest that long-term diabetes insipidus might lead to irreversible changes in renal function, probably in people with other risks for renal disease. Evidence of abnormalities suggests a renal or thyroid work-up, respectively, is indicated. Conventional Antipsychotics At about the time lithium was being studied for mania, French physicians were using chlorpromazine as a pre-anesthetic and noted that it seemed to calm agitated patients. It was then tried in a group of agitated psychotic patients, who dramatically improved. As discussed in Chapter 5, mania is a state of excessive dopaminergic neurotransmission, so that dopamine antagonists are essentially universally effective in its treatment. For several decades, conventional antipsychotics, along with lithium, were the standard treatments for mania. However, as other drugs were identified, conventional antipsychotics fell into disfavor for bipolar disorder for two primary reasons. Second, conventional antipsychotics have not been found to be effective maintenance agents in bipolar disorder; in particular, they do not appear to prevent, and may even hasten, depressive recurrences. Nonetheless, these drugs remain third-line agents for acute mania in cases in which lithium, atypical antipsychotics or antiepileptics are either ineffective or not tolerated. Dosing for these compounds for the treatment of mania is typically the same as used for treating acute psychosis in schizophrenia. Although the rate and time course of treatment response is similar to lithium, the sedating effects particularly of low-potency antipsychotics are more pronounced and may therefore provide more rapid benefit for agitated patients earlier in treatment. The side effects of representative conventional antipsychotics are listed in Table 7. First, divalproex has a much wider therapeutic range than lithium and is much less toxic at the high end of the range. Practically, given this wide therapeutic range, dosing is much more dependent on symptom improvement and tolerability than serum levels as compared with lithium. Second, pseudoloading dose strategies that predict a final steady-state dose in the therapeutic range were developed and well tolerated. Serum levels should be checked every few days during initial titrations, but once response is established, these can be largely guided by clinical response and tolerability. Divalproex demonstrates less specificity, but broader efficacy than lithium, in that its response is similar independent of the presence of mixed states or multiple prior affective episodes. As noted, it did not separate from placebo on the primary maintenance study, although other studies and extensive clinical experience suggest divalproex has some relapse prevention qualities. Once the individual is stabilized, serum levels can be checked whenever performing routine follow-up of potential adverse effects of divalproex (Table 7. Ingirlsandyoungwomen,divalproex has been associated with increased rates of polycystic ovarian syndrome that can be significant and affect fertility; consequently, divalproex should be used carefully in these individuals and, when it is used, reproductive history should be monitored. Finally, rare but potentially dangerous side effects include hepatotoxicity, hemorrhagic pancreatitis, and thrombocytopenia. Consequently, hepatic profiles and blood counts are recommended perhaps annually or with symptoms; amylase should be checked with any significant abdominal symptoms. Although since then it seems less likely that bipolar and epileptic disorders share common etiopathological mechanisms, preliminary success with carbamazepine suggested alternative approaches to treating bipolar disorder. It induces the enzymes that metabolize it, leading not only to complex drug-drug interactions, but also to changes in its own serum levels over time. It can also decrease serum levels of oral contraceptives so that they become ineffective. Older studies suggest carbamazepine may be an effective antidepressant and may perhaps prevent relapse of affective episodes in bipolar disorders, although few, if any, of these studies would meet current double-blind, placebo-controlled design standards. Nonetheless, for the treatment of mania, carbamazepine is typically started at 200 mg twice per day then increased based on tolerability, clinical response, and serum levels. As noted, serum-level monitoring can be useful to adjust dosing while awaiting a response (and avoiding side effects) and will need to be repeated for several weeks as carbamazepine autoinduces its own metabolism. Serum levels can be followed as other laboratory values are checked to monitor for adverse effects. Up to 0% of individuals on carbamazepine develop a rash, of which a small percent progress to Stevens-Johnson syndrome, which can be life threatening. Consequently, it is commonly combined in the treatment of bipolar disorder with medications with the opposite profile. Divalproex increases the serum levels of lamotrigine, requiring slower titration and a lower target dose when lamotrigine is added. Carbamazepine decreases lamotrigine serum levels, often requiring an increase in the dose of the latter when this combination is used. Topiramate demonstrated initially promising results in small mania clinical trials, but then failed in large placebo-controlled studies in adults. In adolescents, one double-blind trial suggested that topiramate may be an effective antimanic in this younger age group, although the effect size was modest. For children less than 0 years old, downward adjustments must be made based on weight. Common side effects include sedation, fatigue, paresthesias, and cognitive impairment, particularly word-finding difficulties. In particular, topiramate is associated with word-finding difficulties relatively unique to its administration. Unlike most bipolar treatments, topiramate is associated with weight loss rather than weight gain. Oxcarbazepine is chemically similar to carbamazepine, and several small clinical trials suggested that it is an effective antimanic, but data are limited. Dosing is typically that used for epilepsy, namely starting with 600 mg per day and increasing up to 2,400 mg per day based on tolerability and response. Oxcarbazepine produces side effects similar to carbamazepine, although it tends to be better tolerated and the severe adverse effects. Gabapentin was widely prescribed for bipolar disorder for several years in the 990s, until studies demonstrated it was no better (and perhaps even worse) than placebo in the treatment of bipolar mania. It has no role in the treatment of acute affective episodes or relapse prevention in bipolar disorder, although it may be an alternative anxiolytic to benzodiazepines or antidepressants for some individuals. Atypical Antipsychotics Although a specific definition of an "atypical" antipsychotic separating them from "conventional" antipsychotics has been somewhat elusive, the best functional definition is related to binding at the dopamine D2 receptor. Conventional antipsychotic D2-receptor binding is such that the dose range between these two occupancy rates is very narrow and difficult to target clinically. In contrast, atypical antipsychotics either possess a larger dose range between these occupancy rates allowing more "targeted" dosing. This slow titration is believed to decrease the risk of Stevens-Johnson syndrome, the major side-effect concern with lamotrigine. Moreover, unlike conventional antipsychotics, some of these compounds appear to be effective at preventing and even treating bipolar depression. These drugs do not require serum levels, but are dosed based on clinical response and tolerability; typical ranges are provided in Table 7. Despite variable half-lives, all can be dosed once daily, although sometimes multiple dosing is used to take advantage of "useful" side-effects, such as sedation in an agitated individual. In general, these drugs have been associated with weight gain and metabolic abnormalities, namely hyperlipidemia and type-2 diabetes. Clozapine Clozapine is the original atypical antipsychotic based on its D2 dopamine-binding properties. Although it represented a major advance in managing treatment-resistant schizophrenia, and it spawned the search for the next generation of antischizophrenia treatments, it is relatively uncommonly used in bipolar disorder. Primarily, it is reserved for use in bipolar individuals with marked treatment resistance to other first- and second-line interventions. It has a complex side-effect profile that includes high rates of sedation, hypersalivation, tachycardia, dizziness, hypotension, and weight gain. Risperidone is an effective antimanic and maintenance treatment (primarily of manic relapse). The more common side effects include sedation, orthostatic hypotension, and dizziness. Finally, risperidone causes a dramatic increase in prolactin that may have long-term negative effects on reproductive functions and bone density. Ziprasidone Ziprasidone is an effective antimanic that may improve relapse prevention of lithium and divalproex when used in combination. It failed in bipolar depression studies, so is not recommended for the treatment of this phase of the illness. In mania, ziprasidone is typically initiated at 80 mg per day (40 mg bid) and titrated as tolerated and by response up to 60 mg per day. Ziprasidone is generally well tolerated, although it may cause dizziness or agitation. Nonetheless, it should be prescribed cautiously in people with personal or family histories of cardiac arrhythmias. Aripiprazole Aripiprazole is effective as an antimanic and maintenance agent (primarily for manic relapse) in bipolar disorder. Olanzapine Olanzapine is an effective antimanic and maintenance agent and may be a weak antidepressant (which improves when combined with fluoxetine). In adults, it is typically started at 0 mg per day and can be increased to 30 mg per day; lower doses are commonly used in children. The most problematic adverse effects associated with olanzapine are sedation, which appears to persist throughout its treatment course, and weight gain. Indeed, olanzapine is associated with the highest weight-gain liability of any of these recommended treatments. However, it is associated with akathisia in general and with elevated liver function tests and prolactin in children. Psychopharmacologic Management sensitive to side effects) and titrated within a few days to a target dose of 0 mg. The most common and problematic side effect for aripiprazole is nausea and vomiting, particularly initially. Aripiprazole has relatively little weight-gain liability in adults, although is associated with weight gain in younger individuals. Its use has been associated with an increased risk for stroke in elderly individuals with dementia. Lurisadone Lurisadone is an effective treatment for bipolar depression, but has not yet been studied as a maintenance agent or for mania.

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