Need For Venous Access Research Articles

Pacing Over the Guidewire in Cardiac Structural Intervention: A Practical Guide

Left ventricular access for aortic valve intervention provides the opportunity to deliver rapid pacing over the guidewire for device positioning and deployment. Temporary pacing delivered via the left ventricle can obviate the need for venous access and has been shown to be a safe alternative to temporary right ventricular pacing. The technique requires some basic knowledge and experience in temporary cardiac pacing. We outline safe practical steps and common pitfalls in using this technique.

Intranasal Ketamine and Its Potential Role in Cancer-Related Pain.

Cancer-related pain continues to be a significant therapeutic challenge, made more difficult by contemporary opioid use and diversion concerns. Conventional treatment using a tiered approach of nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and adjuvant agents is limited; and alternatives are needed for patients with rapidly progressing pain and those who develop hyperalgesia and tolerance to opioids. Ketamine, an N-methyl-d-aspartate (NMDA) selective antagonist, has historically been used for anesthesia in adult and pediatric populations but has also been investigated for depression, bipolar disorder, and general and postoperative pain management. As an analgesic, low-dose ketamine decreases morphine requirements and rates of nausea and vomiting, suggesting a potentially beneficial role in cancer-related pain. Ketamine is typically administered intravenously and has a rapid onset of action with a relatively short half-life (2-3 hours) but is inconvenient for use in an ambulatory setting. Oral bioavailability is low and erratic, limiting application of this route for chronic use. Intranasal administration has a number of potential advantages, including avoidance of first-pass hepatic metabolism, no need for venous access, ability to repeat doses quickly, and rapid absorption. Although early studies of intranasal ketamine are promising in a number of indications, information is more limited in its use as an adjunct in cancer-related pain. We review the background, rationale, pharmacokinetics, and clinical and safety data using intranasal ketamine as an adjunctive agent and its potential in cancer-related pain.

Early application of the Ponseti casting technique for clubfoot correction in sick infants at the neonatal intensive care unit.

The treatment of congenital clubfoot has been changing rapidly since the mid-1990s with the worldwide use of the Ponseti method for serial casting and limited operative interventions. This method was first applied for isolated clubfeet and later on for other types of clubfoot (teratologic, residual, and neurogenic). Premature babies sustaining clubfoot commonly suffer from additional congenital and acquired medical problems. These may postpone clubfoot management until urgent issues are resolved. The current study describes early initiation of treatment of clubfoot in premature babies at the neonatal intensive care unit (NICU) and their outcomes. The study group included all babies diagnosed with clubfoot and managed in the NICU (for any etiology) between 2006 and 2012. Management was based on the Ponseti protocol for serial casting. We also report on neonates who died in the NICU before or during treatment. We specifically describe adverse events of early casting and situations necessitating removal of casts or termination of treatment. We diagnosed and treated 20 neonates with clubfoot (four females and 16 males, 10 bilateral cases). Gestational age ranged from 27 weeks to term. Eight were identified with clubfoot by prenatal sonographic survey and 10 were diagnosed with a defined syndrome. Seven had respiratory support, including one with a chest drain (50%). Length of stay in the NICU ranged from 3 to 90 days. Four neonates died while in the NICU (all syndromatic). In the remaining 16 cases, treatment began as early as medically possible. The first cast was applied within the first week of life in 14 cases. A total of 75 casts were applied during the study period. Three casts (4%) were removed because of leg edema or a need for venous access. Casts were routinely replaced every 4-7 days. Achilles tenotomies were performed in the NICU for babies achieving satisfactory correction. At last follow-up, 10 children were independent walkers and six were nonambulatory; all showed successful correction of clubfeet. The results of this study show that in most cases, clubfoot treatment is feasible and effective within the first week of life. Instances necessitating immediate cast removal are highlighted. Although while facing acute life-threatening medical problems, the treatment of clubfoot may not be considered a priority, most neonates will grow up into independent individuals; thus, every effort should be made to initiate the best clubfoot management with minimal delay.

Heparin for the treatment of thrombosis in neonates.

Among pediatric patients, newborns are at highest risk of developing thromboembolism. Neonatal thromboembolic (TE) events may consist of both venous and arterial thromboses and often iatrogenic complications (eg, central catheterization). Treatment guidelines for pediatric patients with TE events most often are extrapolated from the literature regarding adults. Options for the management of neonatal TE events include expectant management; nitroglycerin ointment; thrombolytic therapy or anticoagulant therapy, or a combination of the two; and surgery. Since the 1990s, low molecular weight heparin (LMWH) has become the neonatal anticoagulant of choice. Reasons for its appeal include predictable dose response, no need for venous access, and limited monitoring requirements. The overall major complication rate is around 5%. Whether preterm infants are at increased risk is unclear. No data are available on the frequency of osteoporosis, heparin-induced thrombocytopenia (HIT), or other hypersensitivity reactions in children and neonates exposed to LMWH. To assess whether heparin treatment (both unfractionated heparin [UFH] and LMWH) reduces mortality and morbidity rates in preterm and term newborn infants with diagnosed thrombosis. The intervention is compared with placebo or no treatment. Also, to assess the safety of heparin therapy (both UFH and LMWH) for potential harms.Subgroup analyses were planned to examine gestational age, birth weight, mode of thrombus diagnosis, presence of a central line, positive family history for genetic disorders (thrombophilia, deficiency of protein S and protein C, methylenetetrahydrofolate reductase [MTHFR] mutation), route of heparin administration, type of heparin used, and location of thrombus (see "Subgroup analysis and investigation of heterogeneity"). We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4), MEDLINE via PubMed (1966 to May 9, 2016), Embase (1980 to May 9, 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to May 9, 2016). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. Randomized, quasi-randomized, and cluster-randomized controlled trials comparing heparin versus placebo or no treatment in preterm and term neonates with a diagnosis of thrombosis. We used the standard methods of the Cochrane Neonatal Review Group. Two review authors independently assessed studies identified by the search strategy for inclusion. Our search strategy yielded 1160 references. Two review authors independently assessed all references for inclusion. We found no completed studies and no ongoing trials for inclusion. We found no studies that met our inclusion criteria and no evidence from randomized controlled trials to recommend or refute the use of heparin for treatment of neonates with thrombosis.

Emerging and future therapies for hemophilia.

The evolution of care in hemophilia is a remarkable story. Over the last 60 years, advances in protein purification, protein chemistry, donor screening, viral inactivation, gene sequencing, gene cloning, and recombinant protein production have dramatically enhanced the treatment and lives of patients with hemophilia. Recent efforts have produced enhanced half-life (EHL) clotting factors to better support prophylaxis and decrease the frequency of infusions. Medical needs remain in the areas of alternate modes of administration to decrease the need for venous access, better treatment, and prophylaxis for patients who form antibodies to clotting factors, and ultimately a cure of the underlying genetic defect. In this brief review, the authors summarize data on EHL clotting factors, introduce agents whose mode of action is not clotting factor replacement, and list current gene therapy efforts.

Venous access in children: state of the art.

The aim of this review is to discuss recent developments in vascular access technology and to highlight those that are particularly relevant to the practitioner. The need for venous access should always be critically assessed in every child, and it is important to use the limited number of suitable veins wisely and to avoid unnecessary attempts. Near-infrared devices make veins visible, but they do not necessarily increase the success rate of peripheral venous puncture. In contrast, ultrasound is now almost universally used for central venous puncture, and it helped to popularize the supraclavicular puncture of the left anonymous vein. The focus has shifted more toward infectious and especially thrombotic complications. Despite the development of new technical devices, successful venous puncture remains heavily dependent on the skills of the operator.

Subcutaneous Immunoglobulin (SCIG) in Responders to Intravenous Therapy with Chronic Immune Thrombocytopenia (ITP)

Introduction. Immune thrombocytopenia (ITP) is characterized by platelet destruction due to the presence of platelet antibodies. This phenomenon is associated with impaired platelet production by bone marrow. Short-course corticosteroids and high-dose intravenous immunoglobulins remain the first-line treatments. Aim of this study was to test if SCIG is equally effective and can be less expensive than hospital-based IVIG in treating chronic-ITPMethodsSeven-ITP patients aged between 13-52 years were given liquid intravenously immunoglobulin (IVIg) stabilized with proline in a dose of 400 mg/kg per day for 5 consecutive days.The median time since ITP diagnosis was 18 months (range, 16 – 38) Median (range) baseline platelet count 19 (3 – 32) x 109/L.,median of 2 (1 – 3) prior ITP therapies. Furthermore, none of of the subjects was a good candidate for TPO-receptor agonists (romiplostim and eltrombopag) because of age or other comorbidities.6 / 6 had a good response to the first 5 day course of gammaglobulin therapy, (platelet count ≥50 × 10(9) /l and ≥2× baseline). The peak platelet count occurred within 7 days from the beginning of the therapy. Only in one patient the platelet count peak took place after 12 days. During the first year of treatment, only one of seven initial responder patients achieved CR(defined as platelet count ≥ 100 * 10^9/L measured on two occasions > 7 days apart and the absence of bleeding) and was excluded from the study. After a loading dose of 2 g/kg over 2 days of IVIg, home SCIG of 8 gr total weekly dose was started by 87,3% (6/7) to maintain platelet counts in the target range of 50–100x109/L.Results5/6 patients reached the target. One patient achieved CR during the maintenance therapy.No untoward reactions necessitating cessation of therapy were encountered during this study. The most common side effect observed was headache.ConclusionApplication of SCIG was well tolerated, easy to manage, and led to stabilization of the disease course.The therapy facilitates home therapy, as the infusion technique is easy for children, adults and elderly people to learn and there is no need for venous access. SCIG home therapy leads to significantly improved life situations for the patients; the SCIG home therapy regimen in particular reduces the costs of treatment. Overall costs per patient were strongly reduced in SCIG in comparison to IVIg.SCIG may represent an effective new therapeutic option in chronic ITP. DisclosuresAbruzzese:novartis, bristol myers squibb, ariad, pfizer, takeda: Consultancy, Membership on an entity’s Board of Directors or advisory committees.

Subcutaneous IgG in neurologic diseases

Subcutaneous administration of IgG (SCIG) has become widely used in primary immune deficiency diseases but it has only recently been studied for maintenance therapy in autoimmune peripheral neuropathies, such as chronic idiopathic demyelinating polyneuropathy and multifocal motor neuropathy. Weekly self-administration of SCIG is safe and well-tolerated, and results in steady-state serum IgG levels, as contrasted with the peaks and troughs of monthly immune globulin (human) for intravenous use. Freedom from the need for venous access or medical personnel for infusions, flexibility in scheduling, convenience of home therapy, and improved clinical stability due to the steady-state IgG levels, lead many patients to prefer SCIG to immune globulin (human) for intravenous use. Long-term studies are needed to determine if the constant IgG levels and clinical stability translate into better long-term outcomes.

El cardiodesfibrilador totalmente subcutáneo

The implantable cardioverter-defibrillators (ICD) is a therapy for the prevention of sudden cardiac death. Complications with implant have been associated mainly with transvenous lead insertion. Difficulties in achieving venous access can occasionally result in failed ICD implantation. Lead failures remains a major limitation and often require removal. This procedure is associated with important morbidity and mortality. To eliminate the need for venous access, Bardy et al. designed an entirely subcutaneous ICD system. The subcutaneous ICD consists of a 3-mm tripolar parasternal electrode positioned parallel to the left of the sternal midline and guided exclusively by anatomical landmarks without fluoroscopy. The pulse generator is positioned over the sixth rib between the midaxillary line and the anterior axillary line. The device delivers a maximum of only 80-J shocks. Ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two tests to ensure a margin of safety. A demand pacing at 50 beats per minute is available for 30 seconds after a shock. These studies are preliminary but the system will need to be employ in a long-term, randomized, prospective, multicenter clinical trials.

Emergency Ultrasound Diagnosis of Deep Venous Thrombosis in the Pediatric Emergency Department

The diagnosis of deep venous thrombosis (DVT) in patients presenting to the emergency department (ED) has traditionally been limited to examinations by radiologists and ultrasound technicians. Although contrast venography is considered the criterion standard for diagnosis of DVT, time, personnel, cost, exposure to radiation, and the invasive nature of the study (need for venous access) potentially limit the ability to perform the study in an emergent setting. Ultrasonography is an alternative method for thrombus detection and is widely preferred. However, in many health care settings, consultative ultrasound services may not be available immediately, especially after hours and on weekends. Based on recent studies demonstrating accuracy in adult patients, emergency sonographic evaluation of DVT by emergency physicians is considered a core emergency ultrasound application and is recently recommended as standard training to all emergency medicine residents. The diagnosis of DVT in children by emergency ultrasound in the pediatric ED has not been previously described. We present 3 cases of DVT in adolescents identified by emergency ultrasound evaluation in the pediatric ED.

An Entirely Subcutaneous Implantable Cardioverter–Defibrillator

Background Implantable cardioverter–defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. Methods First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. Results The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous I...

Improved Quality of Life, Immunoglobulin G Levels, and Infection Rates in Patients with Primary Immunodeficiency Diseases during Self-Treatment with Subcutaneous Immunoglobulin G

Primary immunodeficiency diseases (PIDDs) include a large class of genetically heterogeneous disorders which predispose patients to significant risk of serious and chronic/recurrent infections, as well as reduced quality of life (QoL). Intravenous immunoglobulin (IVIG) therapy improves the well being of PIDD patients; however, the need for venous access and potentially severe side effects frequently require administration in medical facilities. We evaluated the long-term (12-month) experience with home-based self infusions of subcutaneous immune globulin (SCIG) in patients with PIDD on health-related QoL, rates of serious bacterial infections, and all other infections. Adults (n = 42) and children (n = 9) with PIDD, previously treated with clinic-based IVIG, were trained to self administer SCIG at home. QoL (SF-36(R) and CHQ-PF50 questionnaires), serious bacterial infections, serum immunoglobulin G (IgG) levels, overall infections, and incidence of adverse events were recorded at predetermined intervals. All patients had improved perceptions of general health (adults P = 0.047, children P = 0.037). Adults also had marked improvement in the bodily pain and vitality assessments, and parents had improved perceptions of personal and family activities. Serum IgG levels were maintained at mean levels 25% higher than previous troughs on IVIG. There were 162 infections overall for an annual rate of 3.42/patient, but only 1 serious bacterial infection was observed (0.03/patient/yr). An average of 4.5 days/yr was missed from work or school per patient. Home SCIG therapy was safe and led to improved perceptions of general health, higher serum IgG levels, and very low rates of infections and days missed from work/school.

An Entirely Subcutaneous Implantable Cardioverter–Defibrillator

Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)

Pharmacokinetics of fentanyl after subcutaneous administration in volunteers

Pain relief using intermittent subcutaneous injections of an opioid (e.g. morphine) avoids the need for venous access and does not require complex or expensive pumps and devices. Although data on the pharmacokinetics of subcutaneous morphine exist, there are no comparable data for fentanyl in healthy volunteers. Therefore, the aim of this study was to characterize the pharmacokinetics of 200 microg fentanyl administered as a single bolus dose via the subcutaneous route in healthy opioid-naive volunteers. Nine healthy male volunteers were given 200 microg of subcutaneous fentanyl for more than 30 s. Opioid effects were blocked by administration of naltrexone. Venous blood samples taken at intervals from 5 min to 10 h after the dose were assayed using a liquid chromatography-mass spectrometry method. Pharmacokinetic data were analysed using a noncompartmental analysis approach. After subcutaneous bolus dose administration, the median maximum concentration of fentanyl was 0.55 ng ml(-1) (range 0.28-0.87 ng ml(-1)), reached at a median time of 15 min (range 10-30 min). The terminal half-life was 10.00 h (range 5.48-16.37 h). Absorption of subcutaneous fentanyl was relatively rapid and similar to the rate of absorption previously reported for subcutaneous morphine; the terminal half-life for fentanyl was substantially longer (10 h) than that of morphine (2.1 h), and blood concentrations were no more variable than that after administration by other nonintravenous routes.

The Association of Malignant Hyperthermia and Unusual Disease: When You’re Hot You’re Hot, or Maybe Not

Barbara W. Brandom, MD This issue of Anesthesia & Analgesia brings together a collection of papers focused on the prevalence of malignant hyperthermia (MH), the possible association of exertional heat illness with MH, and the association of myotonias, muscular dystrophies, core myopathies, and enzymopathies with MH. Although these papers have a global perspective, a number of them originate from a 1-day symposium held during the 2008 Society for Pediatric Anesthesia Spring meeting in San Diego. The purpose of this symposium was to discuss the relationship of these disorders to MH in light of what is currently understood with regard to their molecular basis and to identify the clinical challenges that these disorders present to pediatric anesthesiologists. Because a number of case reports and small series have described patients with these disorders and clinical symptoms of increased temperature, arrhythmias, rhabdomyolysis, and/or hyperkalemia during or after anesthesia, the clinician is confronted with the question of whether there is a true association between these disorders and MH. In view of the relative rarity of these disorders, establishing an association between these disorders and MH becomes difficult. One of the many challenges of providing anesthesia for pediatric patients is that rare or unusual diseases often remain undiagnosed in infancy and early childhood because they have not produced sufficient physiological impairment or clinical signs and symptoms to merit evaluation. This is especially true in pediatric patients with underlying neuromuscular disorders or enzymopathies undergoing anesthesia for muscle biopsies. In addition, critical incidents during anesthesia occur more frequently in infants and small children compared with older children and adults. Airway and cardiovascular instability frequently occurs on induction of anesthesia in infants and small children. Induction of anesthesia by inhalation of potent anesthetic is a method that can facilitate airway management. To further complicate the anesthetic management, IV access is often a challenge in pediatric patients. The need for venous access can become a major determinant of anesthetic technique. Usually the pediatric patient who presents for a muscle biopsy has only a tentative diagnosis and therefore the risk of MH in this patient is unknown. Part of the dilemma in assessing MH risk in these patients is understanding the limitations in the MH literature and numerous case reports describing adverse anesthetic events. The “gold standard” for confirming a diagnosis of MH has been the in vitro contracture test. The sensitivity and specificity of the caffeine halothane contracture test has been determined in patients who did not have clinical myopathy. The sensitivity of a diagnostic test is the probability of that test being positive when the patient has the disease. Specificity of the test is the probability of a negative or normal test result when the patient does not have the disease. Any diagnostic test with high sensitivity has a low false negative rate, and tests with a low specificity have a high incidence of false positives. The From the *Department of Anesthesiology, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine; and †University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Accepted for publication June 19, 2009. Barbara W. Brandom has received research funding from the Malignant Hyperthermia Association of the United States (MHAUS). The North American MH Registry (which is financially supported by MHAUS) may be affected financially by this publication. MHAUS is a not-for-profit organization focused on MH. Peter J. Davis is a consultant for EISAI Pharmaceuticals, Abbott Laboratories, and Hospira. Address correspondence and reprint requests to Peter J. Davis, MD, Department of Anesthesiology, Children’s Hospital of Pittsburgh, 45th and Penn, Pittsburgh, PA 15201. Address e-mail to davispj@anes.upmc.edu. Copyright © 2009 International Anesthesia Research Society DOI: 10.1213/ane.0b013e3181b493d4

Erfahrungen mit einem abwerfbaren temporären Vena cava Filter

Evaluation of the feasibility of implantation and explantation and evaluation of the efficacy of a detachable and retrievable temporary vena cava filter. The temporary vena cava filter "OptEase" (Cordis) is a nitinol filter derived from the "TrapEase" (Cordis) permanent filter, which is implantable transjugularly or transfemorally. In contrast to other temporary filters, this type can be detached and is not fixed on a catheter during implantation. Therefore, it is usable as a temporary as well as a permanent filter which can be retrieved up to 12 days after detachment with a special catheter using the loop technique. The "OptEase" filter was implanted in 11 patients ranging in age from 19 to 82 (mean age 30 years). In 10 patients the filter was transfemorally implanted and explanted. In 1 patient implantation was performed transjugularly prior to surgery and explantation was performed transfemorally after surgery. All patients had a deep vein thrombosis or iliac vein thrombosis. In 3 patients the filter was implanted prior to surgery. In 2 patients pulmonary embolism was identified. In 5 patients the filter was implanted prophylactically because of deep vein thrombosis according to interdisciplinary diagnosis. No pulmonary embolism occurred during implantation. All filters were able to be retrieved without complications using the loop technique on the 6th, 8th, 12th and 13th day. No captured thrombus material was in the filter. This new vena cava filter type is an easily implantable and retrievable system. Since this filter type is detachable without a need for venous access during implantation, there are no sterility problems. The filter can be left in the vena cava as a permanent system if explantation is not indicated.

Immunoglobulin Treatment for Primary Antibody Deficiencies

Adults and children with primary antibody deficiencies are prone to bacterial infections affecting the respiratory tract and gastrointestinal canal. To prevent or alleviate infections, replacement therapy with IgG is needed, usually on a lifelong basis. The IgG can be administered intramuscularly, intravenously, or subcutaneously. Subcutaneous IgG (SCIG) therapy, using small portable pumps for once-per-week self infusions, has shown many advantages compared with the two other routes of administration. This review highlights findings from international studies and demonstrates that: (i) SCIG therapy is safe, with very few adverse effects; (ii) the therapy can be used for patients with previous adverse effects to intravenous administration of IgG; (iii) the therapy leads to high serum IgG levels and good protection against infections; (iv) the therapy facilitates home therapy, as the infusion technique is easy for children, adults and elderly people to learn and there is no need for venous access; (v) SCIG home therapy leads to significantly improved life situations for the patients; (vi) the SCIG home therapy regimen in particular reduces the costs of treatment.

Update on treatment regimens: Prophylaxis versus on-demand therapy

Prophylaxis, or the routine scheduled replacement of clotting factor concentrate in patients with hemophilia, greatly decreases episodes of joint hemorrhage and effectively prevents the development of chronic joint arthropathy and disability. Despite clear evidence of its effectiveness and the fact that it is recommended by international authorities, prophylaxis still is not widely accepted in the hemophilia community. In the United States, approximately half of children with severe hemophilia A and one third of those with hemophilia B are on prophylactic regimens. Factors limiting acceptance include the need for venous access, factor availability, poor acceptance of injection therapy, safety concerns, cost, and a perceived lack of need. Questions remaining to be answered include the reasons for inter-individual variability in bleeding patterns, predictors for and reversibility of joint damage, and the optimal regimen for prophylaxis. A need exists for validated and standardized outcome measures in future research, as well as for research into factors that affect families' adherence to prophylactic regimens for their children.

Internal Cardioversion of Atrial Fibrillation: New Information

For more than 30 years transthoracic external cardioversion has been an established method for the restoration of sinus rhythm in patients with persistent atrial fibrillation. It was first described by Lown in 1963 [1]. Though the success rate for external cardioversion ranges from 60–90% [2–4], there is reduced efficacy in those patients with a high body-mass index and an increased transthoracic diameter [5]. The method of internal cardioversion for restoration of sinus rhythm using transvenous electrodes has been reported in several animal [6,7] and human studies [8–15]. Cooper et al. [6] tested multiple electrode configurations in a sheep model of atrial fibrillation. They demonstrated that the optimal single current pathway for internal atrial defibrillation employed two electrodes that surrounded both atria (e.g., right atrial appendage and distal coronary sinus). Similar results have been reported in several human studies [12–14]. Internal cardioversion has been shown to be superior to conventional external cardioversion in terms of primary success rate, energy requirements and the need for sedation; this superiority holds especially true for patients with a high body mass index of >25 kg/m2 and increased transthoracic diameter [15]. The initial human data has been collected using two separate catheter for internal cardioversion. Though this approach demonstrated some advantages, there are also clear disadvantages, such as lack of ventricular backup stimulation in cases of post shock bradycardia, prolonged fluoroscopy time and the need for venous access via primarily the lower limb. These disadvantages increase the risk of bleeding complications, especially in patients with anticoagulation. Recently published data have demonstrated the benefit of a single lead catheter with two shock arrays on a balloon guided pulmonary artery catheter, when compared to the previous two catheter technique [12]. Optional ventricular backup pacing, preferable venous access via the upper limb, reduced procedural and fluoroscopy time are the major advantages. This new balloon-tipped cardioversion catheter (Figures 1 and 2) resembles a regular Swan-Ganz catheter. A guide-wire introduced via a central lumen allows facilitated searing and positioning of this device. The central lumen also provides means to draw blood samples, infuse drugs or perform haemodynamic measurements (pulmonary artery and wedge pressure). The proximal and distal high-energy electrode arrays for internal defibrillation consist of six 0.5 cm long platinum rings with a total surface area of 2.4 cm2 for each array. The middle ring of the proximal array is connected individually for atrial sensing and pacing, while the others are connected in parallel (atrial array). One pole located in the right ventricular outflow tract—between both arrays— serves for ventricular pacing and sensing. The six distal pulmonary rings are connected in parallel for internal cadioversion shock delivery. For cardioversion with this new device an electrode configuration in the right atrium and left pulmonary artery is suggested. A randomized trial could demonstrate that this configuration provides a homogeneous electrical field for effective cardioversion, and slightly higher energy requirements compared to a lead position in the right atrium and distal coronary sinus [12], as described earlier. However, the use of single lead catheters with a shock array position proximal in the right atrium and distal in the left pulmonary artery has contributed to facilitate the procedure of internal cardioversion of atrial fibrillation considerably. Ventricular backup pacing is an important safety tool, not only for a subgroup of patients with post shock bradycardia, but also for bradycardia after the administration of antiarrhythmic drugs or beta-blockers. The possibility of post shock atrial pacing also offers new therapeutic options in preventing the early recurrence of atrial fibrillation. Immediately after cardioversion 60% of all patients develop premature atrial contractions [16]. Recently published data suggest that short coupling intervals of the premature atrial beat predict an early relapse of atrial fibrillation [16]. Heterogeneity of refractoriness and conduction give way for a premature stimulus to reinduce atrial fibrillation. Immediately after cardioversion, electrical remodeling has shortened the

Intravenous immunoglobulins as therapeutic agents.

Intravenous immunoglobulins are stable monomeric pooled human IgG preparations for therapeutic use. Three intravenous immunoglobulins licensed in the United States are generally therapeutically equivalent. Intravenous immunoglobulin is the preferred agent for replacement therapy for most patients with primary or secondary antibody immunodeficiency because of the rapidity and ease of giving large quantities of IgG, even by self-administration. Disadvantages of intravenous immunoglobulins include frequent (approximately 10%) but usually not serious side effects, the need for venous access (often difficult in infants and young children), and high cost. Intravenous immunoglobulins are also beneficial in the prevention of certain viral infections, such as cytomegalovirus pneumonia and varicella; they may also have a synergistic effect with antibiotics in certain bacterial diseases. Intravenous immunoglobulin has also been used successfully in the management of idiopathic thrombocytopenia purpura, Kawasaki disease, and certain autoimmune diseases. Intravenous immunoglobulin may also be of use in certain high-risk and premature newborns.