Leadless Pacemakers

Leadless or transcatheter pacemakers have recently been introduced to market with important benefits and some limitations. Implanted entirely within the right ventricle, these devices eliminate the need for transvenous pacing leads and pacemaker pockets and thus reduce the risk of infections and lead-related problems. Currently, they offer only VVI/R pacing and they cannot provide atrial sensing, antitachycardia pacing, or AV synchrony. They offer a number of features (such as rate response) and electrogram storage, albeit more limited than in a transvenous system. Real-world clinical data are needed to better comment on projected battery life, which manufacturers suggest will be at least equivalent to transvenous devices. Extracting an implanted leadless pacemaker remains a challenge, although proprietary snare and removal systems are available. However, a leadless pacemaker at end of service may be programmed to OOO and left in place; a revised device may be implanted adjacent. These innovative new devices may have important uses in special populations. Initial data on implant success and adverse events are favorable. Currently, there are two leadless pacemakers available: the Micra™ device by Medtronic and the Nanostim™ device by Abbott (formerly St. Jude Medical)

Atrial Fibrillation and the Role of Thumb ECGs

Atrial fibrillation (AF) may be underdiagnosed, and there is much that remains unknown about this prevalent and potentially life-threatening arrhythmia. AF epidemiology has been thwarted in part by the fact that about a third of patients with AF have no symptoms, those with symptoms may experience them intermittently or have vague symptoms, and it can be challenging to capture an episode on a 12-lead ECG, which is required for diagnosis. There are many significant knowledge gaps in our understanding of AF etiology and progression. A new user-friendly device that allows for frequent self-monitoring of the heart rhythm has been introduced. With the thumb ECG, patients can record a tracing multiple times a day. A smartphone app will soon allow them to interact with their healthcare providers about these ECG recordings. An ECG parser will allow for an algorithm-directed, rapid, automatic interpretation of these recordings with high specificity and sensitivity. This may help researchers learn more about the so-called silent AF, AF progression (and possible remission), and risk factors for AF. This technology holds great promise for patient care as well as for research into AF

Anticoagulation in Atrial Fibrillation Patients

Atrial fibrillation (AF) is the most common arrhythmia and may cause thromboembolic events, typically stroke. Advances in pharmacological approaches to anticoagulation and groundbreaking large randomized controlled trials of non-vitamin K antagonist oral anticoagulants (NOACs) have changed the paradigm of anticoagulation therapy. Furthermore, observational studies support the efficacy and safety of NOAC. Few studies address the differences among NOACs, but prescriptions should be based on a thorough understanding of their pharmacological differences, including interactions, side effects, reversibility, and practical approach. In a subset of patients with AF, warfarin may still be the preferable option. Consequently, an individualized approach to oral anticoagulation is crucial

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects

Background and Objective Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. Methods In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Results Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max) and area under the plasma concentration-time curve over the dosing interval (AUC0–6) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased Cmax and AUC0–6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (Tmax) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Conclusions Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain

Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a "do ask, do tell" approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with minimal toxicit

Good clinical practice guide for opioids in pain management: the three Ts - titration (trial), tweaking (tailoring), transition (tapering)

ABSTRACT BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial) during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation). Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring). Finally, for those patients for whom transition (tapering) from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. CONCLUSION: We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's): titration (or trial), tweaking (or tailoring), and transition (or tapering). Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non-pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain

The Use of Peripheral mu-Opioid Receptor Antagonists (PAMORA) in the Management of Opioid-Induced Constipation : An Update on Their Efficacy and Safety

Peripherally acting mu-opioid receptor antagonists (PAMORAs) constitute a class of drugs which reverse opioid-induced constipation (OIC) with similar opioid analgesic effects. OIC differs from other forms of constipation in that it is an iatrogenic condition that occurs when an opioid acts on the dense network of mu-opioid receptors in the enteric system, which affect a variety of functions including gastrointestinal motility, secretion, and other factors that can cause bowel dysfunction. Unfortunately, laxative products, bowel regimens, dietary changes, and lifestyle modifications have limited effectiveness in preventing OIC, Opioid-associated adverse effect which occurs in 40% to 80% of opioid patients and may led to cessation of the treatment. PAMORAs are mu-receptor opioid antagonists specifically developed so that they have very limited ability to cross the blood-brain barrier and thus they are able to antagonize peripheral but not central mu-opioid receptors. PAMORAs are designed to have no effect on the analgesic benefits of opioid pain relievers but to relieve but antagonizing the effects of the opioid in the gastrointestinal system. The three main PAMORAS are methyl-trexone (oral or parenteral), naldemedine (oral only), and naloxegol (oral only). Clinical studies demonstrate the safety and efficacy of these agents for alleviating constipation without diminishing the analgesic effect of opioid therapy. The aim of this narrative review to update the current status of PAMORAs for treating OIC in terms of safety and efficacy

¿Es la Buprenorfina una buena opción en el manejo de dolor postoperatorio?

Background: Pain is one of the most feared outcomes of surgery by patients, yet current practices of pain management are suboptimal. Failure to address acute postoperative pain can have a variety of consequences that affect physical and psychological aspects of the patient. Current perioperative pain management normally consists of opioid therapy, which has been a mainstay for many years. However, use of opioids can have moderate risks, including nausea/vomiting, dizziness, and constipation, or more severe risks, including respiratory depression and immunosupression. Aim: In order to address some of the issues surrounding perioperative pain management, a group of key opinion leaders gathered at an international summit to analyze the current practices of perioperative pain management. One of the topics focused on buprenorphine's role in perioperative pain and the information discussed is presented throughout this article. Conclusion: Buprenorphine has been demonstrated to be effective and safe in many postoperative pain models. Its administration versatility, its manageable side effects, and its use in combination with other analgesics allow buprenorphine therapy to be successful in perioperative pain management.Antecedentes: El dolor es uno de los eventos más temidos por los pacientes después de una cirugía, y en la actualidad el manejo del dolor es subóptimo. La falta de control del dolor agudo postoperatorio puede tener una serie de consecuencias que afectan a los aspectos físicos y emocionales de los pacientes. El manejo habitual del dolor postoperatorio se basa en la utilización de opioides, pilar de tratamiento desde hace muchos años. Sin embargo, el uso de opioides puede tener riesgos moderados, como son las náuseas y vómitos, mareos y constipación, o riesgos más severos que incluyen a la inmunosupresión y depresión respiratoria. Objetivo: Para poder determinar algunos de los factores circundantes del dolor postoperatorio, se realizó una reunión cumbre internacional en la que un grupo de líderes de opinión analizó las prácticas habituales de manejo de dolor postoperatorio. Uno de los temas abordados fue el rol de la buprenorfina en el manejo del dolor perioperatorio, y la información discutida se presenta a lo largo de este artículo. Conclusión: La buprenorfina ha demostrado ser eficaz y segura en muchos modelos de dolor postoperatorio. Su versatilidad de administración, sus efectos secundarios manejables y su posibilidad de ser combinada con otros analgésicos hacen que la buprenorfina sea exitosa en el manejo del dolor perioperatorio