IPACK Block Efficacy for Acute Pain Management after Total Knee Replacement: A Review.

PURPOSE OF REVIEW: Patients often experience a significant degree of knee pain following total knee replacement (TKR). To alleviate this pain, nerve blocks may be performed such as the adductor canal block (ACB). However, ACBs are unable to relieve pain originating from the posterior region of the knee. A new type of nerve block known as the IPACK block may be used in conjunction with ACBs as it is designed to inhibit nerve branches innervating this area. In this article, we examine the rationale behind the IPACK procedure, how it is performed, and clinical trials examining its efficacy. RECENT FINDINGS: 5 of the 7 clinical trials examined in this article showed the IPACK + ACB block to show superior efficacy in treating pain following TKR compared to other blocks. These blocks included PMDI+ACB, SPANK+ACB, PAI+ACB, ACB alone, and SCAB. 2 of the 7 clinical trials showed the IPACK + ACB to be less effective in managing patients pain following TKR compared to other blocks which included the CACB and 4 in 1 block. In most instances, the IPACK + ACB showed superior efficacy in managing patients' pain following TKR when compared to other types of nerve blocks. This was determined by measuring usage of opioids, reported postoperative pain, and length of hospital stays following TKR. Thus, we suppose the IPACK block may be used in conjunction with the ACB to effectively reduce patient's pain following TKR.

The Emerging Role of Ketamine in Acute Postoperative Pain Management.

PURPOSE OF REVIEW: Postoperative pain (POP) is among the most unpleasant experiences that patients face after surgery. Interest in and use of N-methyl-D-aspartate (NMDA) receptor antagonists for the management of POP has increased over the years with ketamine being the most popular drug of this class. RECENT FINDINGS: Several randomized controlled trials found that the use of ketamine either alone or in combination with other medications leads to decreased postoperative pain and opioid consumption. However, there are other studies that have not found these benefits. The results as of now suggest that the role of intraoperative ketamine in postoperative pain control varies among different operative procedures. While some studies have shown promise in ketamine's potential use as a postoperative analgesic, there is still a great deal of proposed research and randomized controlled trials needed to deduce the most efficacious and tolerable form and dose of ketamine.

Regenerative Medicine: Pharmacological Considerations and Clinical Role in Pain Management.

PURPOSE OF REVIEW: Low back pain affects at least 80% of individuals at some point in their lifetime and is the fifth most common reason for physician visits in the USA. Treatment of an acute episode of LBP generally includes rest, activity modification, physical therapy, NSAIDs, and patient education. RECENT FINDINGS: A small percentage of patients will develop chronic pain lasting > 6 months duration. Platelet-rich plasma (PRP) is one of the main pillars of regenerative medicine, as its release of bioactive proteins supports the aim of RM of restoring the anatomical function in degenerative conditions. Mesenchymal stem cells (MSCs) are multipotent stem cells, multipotent progenitor cells, or marrow stromal cells found in various body tissues, including bone marrow, lung, and adipose tissue. Evidence from well-designed case-control or cohort studies for the use of PRP and MSCs in lumbar facet joint, lumbar epidural, and sacroiliac joint injections is currently described as level IV evidence. PRP and MSCs are used autogenously to help facilitate the healing process, and their injection has been studied in the long-term management of discogenic low back pain. PRP has been compared to steroid injections in the sacroiliac joint for chronic low back pain, with favorable results. MSCs have also been shown to be useful in intervertebral disc regeneration and treatment of chronic low back pain associated with degenerative disc disease. Currently, the price for these treatments is extremely high, and thus the standard of care continues to be steroid injections and other treatments. This could change, however, with more robust data and research on the safety and long-term efficacy of biologics compared to other interventional management.

Neuropathic Pain and Sickle Cell Disease: a Review of Pharmacologic Management.

PURPOSE OF REVIEW: Sickle cell disease (SCD) remains among the most common and severe monogenic disorders present in the world today. Although sickle cell pain has been traditionally characterized as nociceptive, a significant portion of sickle cell patients has reported neuropathic pain symptoms. Our review article will discuss clinical aspects of SCD-related neuropathic pain, epidemiology of neuropathic pain among individuals with SCD, pain mechanisms, and current and future potential pharmacological interventions. RECENT FINDINGS: Neuropathic pain in SCD is a complicated condition that often has a lifelong and significant negative impact on life; therefore, improved pain management is considered a significant and unmet need. Neuropathic pain mechanisms are heterogeneous, and the difficulty in determining their individual contribution to specific pain types may contribute to poor treatment outcomes in this population. Our review article outlines several pharmacological modalities which may be employed to treat neuropathic pain in SCD patients.

Regional Anesthesia in Patients on Anticoagulation Therapies-Evidence-Based Recommendations.

PURPOSE OF REVIEW: Anticoagulant use among patients is prevalent and increasing. It is important for anesthesiologists to be aware of patients on anticoagulants while performing regional anesthesia. RECENT FINDINGS: In recent years, the FDA has approved many new anticoagulants. With new drugs coming to the market, new side effect profiles should be considered when treating patients, especially when using regional anesthesia. Both ASRA and European agencies have laid out recommendations regarding anticoagulant use and neuraxial/regional techniques. Regarding newer anticoagulants, the guidelines for discontinuation prior to neuraxial injection are based on pharmacokinetics, including half-life duration for each drug. While each clinical scenario requires an individualized approach, general guidelines can serve as a starting point to help with anesthetic planning and potentially improve patient safety in this evolving field.

Regional Nerve Blocks-Best Practice Strategies for Reduction in Complications and Comprehensive Review.

PURPOSE OF REVIEW: Understanding the etiologies of the complications associated with regional anesthesia and implementing methods to reduce their occurrence provides an opportunity to foster safer practices in the delivery of regional anesthesia. RECENT FINDINGS: Neurologic injuries following peripheral nerve block (PNB) and neuraxial blocks are rare, with most being transient. However, long-lasting and devastating sequelae can occur with regional anesthesia. Risk factors for neurologic injury following PNB include type of block, injection in the presence of deep sedation or general anesthesia, presence of existing neuropathy, mechanical trauma from the needle, pressure injury, intraneural injection, neuronal ischemia, iatrogenic injury related to surgery, and local anesthetic neurotoxicity. The present investigation discusses regional blocks, complications of regional blocks, risk factors, site-specific limitations, specific complications and how to prevent them from happening, avoiding complications in regional anesthesia, and the future of regional anesthesia.

Stem Cell Therapy for Osteonecrosis of the Femoral Head: Current Trends and Comprehensive Review.

PURPOSE OF REVIEW: Osteonecrosis of the femoral head (ONFH) is a common and frequently occurring disease. It is caused by interruption of blood supply with different etiologies. ONFH leads to degeneration and necrosis of the subchondral bone of the femoral head and eventually collapse of the femoral head. ONFH has a high disability rate, seriously affecting the quality of living of patients, and often involves middle-aged and younger people. RECENT FINDINGS: In recent years, the technology and understanding of stem cells and regenerative medicine have been developing rapidly. Numerous studies have reported successful results in the treatment of ONFH by stem cell transplantation. Thus, stem cell transplantation is expected to serve as a new method in the treatment of ONFH. In the present report, therefore, we evaluated current techniques and outcomes utilizing stem cells in the treatment of ONFH. A computer-based online search of PubMed and Cochrane Library databases between January 2006 and June 2017 was performed to search related articles using the keywords of "treatment, stem cell, osteonecrosis of the femoral head" in English language. Literature related to the treatment of ONFH was selected. Our search obtained a total of 161 articles, but only 9 articles met our inclusion criteria and were included in our report. The present review reveals that cell technology has demonstrated good evidence in the treatment of ONFH. However, this technology needs additional in-depth study to better explore and appreciate more ideal ways to overcome difficulties associated with source of cells.

Preoperative Assessment for Ambulatory Surgery.

PURPOSE OF REVIEW: Ambulatory surgery has grown in recent decades in volume and represents a significant number of anesthetics delivered throughout the USA. Preoperative anesthetic assessment in the ambulatory setting has become important because patients with numerous complex comorbidities are now commonplace in this arena. Disease states involving the lungs, the heart, the kidneys, and subpopulations including those who are obese and the elderly commonly receive anesthetics in an ambulatory setting. RECENT FINDINGS: This review presents key aspects of current thinking with regard to preoperative assessment and considerations for different critical disease states and subpopulations that are now being managed under ambulatory surgery. Same day surgery centers require patient safety, and expectations are high for patient satisfaction. Advancements in surgical and anesthetic technique have allowed for more complex patients to partake in ambulatory surgery. Anesthesiologists must be familiar with guidelines, state-of-the-art pain management, and standards of preoperative patient evaluation to accurately stratify patient risk and to advocate for patient safety.

An Analysis of Responses to Defibrotide in the Pulmonary Vascular Bed of the Cat.

Defibrotide is a polydisperse mixture of single-stranded oligonucleotides with many pharmacologic properties and multiple actions on the vascular endothelium. Responses to defibrotide and other vasodepressor agents were evaluated in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure. Lobar arterial pressure was increased to a high steady level with the thromboxane A2 analog U-46619. Under increased-tone conditions, defibrotide caused dose-dependent decreases in lobar arterial pressure without altering systemic arterial and left atrial pressures. Responses to defibrotide were significantly attenuated after the administration of the cyclooxygenase inhibitor sodium meclofenamate. Responses to defibrotide were also significantly attenuated after the administration of both the adenosine 1 and 2 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine and 8-(3-chlorostyryl)caffeine. Responses to defibrotide were not altered after the administration of the vascular selective adenosine triphosphate-sensitive potassium channel blocker U-37883A, or after the administration of the nitric oxide synthase inhibitor L-N-(1-iminoethyl)-ornithine. These data show that defibrotide has significant vasodepressor activity in the pulmonary vascular bed of the cat. They also suggest that pulmonary vasodilator responses to defibrotide are partially dependent on both the activation of the cyclooxygenase enzyme and adenosine 1 and 2 receptor pathways and independent of the activation of adenosine triphosphate-sensitive potassium channels or the synthesis of nitric oxide in the pulmonary vascular bed of the cat.

Novel Local Anesthetics in Clinical Practice: Pharmacologic Considerations and Potential Roles for the Future.

The treatment of pain, both acute and chronic, has been a focus of medicine for generations. Physicians have tried to develop novel ways to effectively manage pain in surgical and post-surgical settings. One intervention demonstrating efficacy is nerve blocks. Single-injection peripheral nerve blocks (PNBs) are usually preferred over continuous PNBs, since they are not associated with longer lengths of stay. The challenge of single injection PNBs is their length of duration, which at present is a major limitation. Novel preparations of local anesthetics have also been studied, and these new preparations could allow for extended duration of action of anesthetics. An emerging preparation of bupivacaine, exparel, uses a multivesicular liposomal delivery system which releases medication in a steady, controlled manner. Another extended-release local anesthetic, HTX-011, consists of a combination of bupivacaine and low-dose meloxicam. Tetrodotoxin, a naturally occurring reversible site 1 sodium channel toxin derived from pufferfish and shellfish, has shown the potential to block conduction of isolated nerves. Neosaxitoxin is a more potent reversible site 1 sodium channel toxin also found in shellfish that can also block nerve conduction. These novel formulations show great promise in terms of the ability to prolong the duration of single injection PNBs. This field is still currently in development, and more researchers will need to be done to ensure the efficacy and safety of these novel formulations. These formulations could be the future of pain management if ongoing research continues to prove positive effects and low side effect profiles.

The Influence of Analgesic Modalities on Postoperative Cancer Recurrence.

The potential for cancer cells to grow and to metastasize depends on complex interactions between inflammatory signals and pathways, immune cells, and elements of the stromal tissue in which they invade. Related to the nature of many cancers, the probability of recurrence can potentially be quite high for some patients. Immunology, lifestyle modifications, timing of disease, genetics, age, gender, and race are only a handful of ways the likelihood of cancer recurrence can be influenced. The quantity, or density, of certain immunological cells or factors, plays a role in the propagation of cancer cells. Opioids are often used in cancer patients for acute postoperative and chronic pain management. While they can produce significant pain relief, the type of analgesic utilized is important, as it may influence cancer propagation. In this regard, certain opioids have been found to increase T regulatory cells while suppressing NK cell function. Morphine may promote tumor neovascularization and expansion. Fentanyl administration significantly diminishes NK-cells and CD8+ cytotoxic T-cells. In a recent meta-analysis, propofol-based anesthesia improved both cancer-free survival and overall survival. COX inhibitors have also shown promise in persevering cancer immune function, as in literature involving ketorolac and celecoxib. In summary, inhaled anesthesia and opioids may contribute to a pro-tumor metastasis environment also known as cancer propagation; whereas propofol and COX inhibitors may provide a better alternative to reduce cancer recurrence and propagation.

Midazolam nasal spray to treat intermittent, stereotypic episodes of frequent seizure activity: pharmacology and clinical role, a comprehensive review.

An intranasal formulation of midazolam, Nayzilam, has been FDA-approved to treat intermittent, stereotypic episodes of frequent seizure activity. Nayzilam is easy to administer and can quickly treat seizures that occur outside of the hospital. The intra-nasal route of administration allows non-medical personal to administer the drug which makes it more accessible and user-friendly in the event of a seizure. Many studies have indicated quick cessation of seizures with Nayzilam compared to rectal diazepam, which has been the standard of care treatment. Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative in times where intravenous administration is not possible.

Novel Regional Nerve Blocks in Clinical Practice: Evolving Techniques for Pain Management.

This review examines the use of novel US-guided nerve blocks in clinical practice. Erector spinae block is a regional anesthesia technique doing by injecting a local anesthetic among the erector spinae muscle group and transverse processes. The phrenic nerve is a branch of the cervical plexus, arising from the anterior rami of cervical nerves C3, C4, and C5. The quadratus lumborum muscle is located along the posterior abdominal wall. It originates from the transverse process of the L5 vertebral body, the iliolumbar ligament, and the iliac crest. US-guided peripheral nerve procedures have a considerable scope of use, including treating headaches and hiccups to abdominal surgical pain, cesarean sections, musculoskeletal pathologies. These nerve blocks have been an effective addition to clinical anesthesia practice. The use of peripheral nerve blocks has improved postoperative pain, lessened the use of opioids and their potential side effects, and decreased the incidence of sleep disturbance in patients. More research should be done to further delineate the potential benefits of these blocks.

Adjuvant Drugs for Peripheral Nerve Blocks: The Role of Alpha-2 Agonists, Dexamethasone, Midazolam, and Non-steroidal Anti-inflammatory Drugs.

Adjuvant drugs for peripheral nerve blocks are a promising solution to acute postoperative pain and the transition to chronic pain treatment. Peripheral nerve blocks (PNB) are used in the brachial plexus, lumbar plexus, femoral nerve, sciatic nerve, and many other anatomic locations for site-specific pain relief. However, the duration of action of a PNB is limited without an adjuvant drug. The use of non-opioid adjuvant drugs for single-shot peripheral nerve blocks (sPNB), such as alpha-2 agonists, dexamethasone, midazolam, and non-steroidal anti-inflammatory drugs, can extend the duration of local anesthetics and reduce the dose-dependent adverse effects of local anesthetics. Tramadol is a weak opioid that acts as a central analgesic. It can block voltage-dependent sodium and potassium channels, cause serotonin release, and inhibit norepinephrine reuptake and can also be used as an adjuvant in PNBs. However, tramadol's effectiveness and safety as an adjuvant to local anesthetic for PNB are inconsistent. The effects of the adjuvants on neurotoxicity must be further evaluated with further studies to delineate the safety in their use in PNB. Further research needs to be done. However, the use of adjuvants in PNB can be a way to help control postoperative pain.

Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review.

Given the typical age onset of schizophrenia, there are tremendous economic and social impacts that extend beyond the person and their families. One critical determinant of the diseases' impact is the patient's adherence to antipsychotic drug treatment. Approved in 2015 for the treatment of schizophrenia, paliperidone palmitate (Invega Trinza, a 3-month injection, noted as PP3M) is a second-generation long-acting injectable antipsychotic medication. Among the different formulations offered for palmitate paliperidone, including the 1 and 3-month formulations, the longer duration 3-month formulation was better at preventing relapse in schizophrenic patients. To date, different formulations of palmitate paliperidone that have been studied on relapse episodes of schizophrenia include once-daily extended-release oral paliperidone (ORAL paliperidone), once-monthly paliperidone palmitate (PP1M), and once-every-3-months paliperidone palmitate (PP3M). Post-hoc analyses show that patients who were withdrawn from PP1M paliperidone had the least risk of relapse, followed by patients withdrawn from PP3M and patients withdrawn from ORAL paliperidone. PP3M was better at preventing relapse compared to ORAL paliperidone. The results demonstrated that 50% of patients who were withdrawn from ORAL paliperidone, PP1M, or PP3M remained relapse-free for ~2, 6, and 13 months, respectively. Compared to PP1M, PP3M is just as safe and effective and has the added advantage of increased adherence related to a longer dose interval, decreasing the risk of relapse.

Supraclavicular vs. Infraclavicular Brachial Plexus Nerve Blocks: Clinical, Pharmacological, and Anatomical Considerations.

Peripheral nerve blocks (PNB) have become standard of care for enhanced recovery pathways after surgery. For brachial plexus delivery of anesthesia, both supraclavicular (SC) and infraclavicular (IC) approaches have been shown to require less supplemental anesthesia, are performed more rapidly, have quicker onset time, and have lower rates of complications than other approaches (axillary, interscalene, etc.). Ultrasound-guidance is commonly utilized to improve outcomes, limit the need for deep sedation or general anesthesia, and reduce procedural complications. Given the SC and IC approaches are the most common approaches for brachial plexus blocks, the differences between the two have been critically evaluated in the present manuscript. Various studies have demonstrated slight favorability towards the IC approach from the standpoint of complications and safety. Two prospective RCTs found a higher incidence of complications in the SC approach - particularly Horner syndrome. The IC method appears to support a greater block distribution as well. Overall, both SC and IC brachial plexus nerve block approaches are the most effective and safe approaches, particularly under ultrasound-guidance. Given the success of the supraclavicular and infraclavicular blocks, these techniques are an important skill set for the anesthesiologist for intraoperative anesthesia and postoperative analgesia.

A Comprehensive Review of Novel Interventional Techniques for Chronic Pain: Spinal Stenosis and Degenerative Disc Disease-MILD Percutaneous Image Guided Lumbar Decompression, Vertiflex Interspinous Spacer, MinuteMan G3 Interspinous-Interlaminar Fusion.

Spinal stenosis is the compression of nerve roots by bone or soft tissue secondary to the narrowing of the spinal canal, lateral recesses, or intervertebral foramina. Spinal stenosis may have acquired or congenital origins. Most cases are acquired and caused by hypertrophy of the ligamentum flavum, enlarged osteophytes, degenerative arthritis, disk herniations, and various systemic illnesses. The ligamentum flavum (LF) is a highly specialized elastic ligament that connects the laminae of the spine and fuses them to the facet joint capsules. There are a number of treatment options available for spinal stenosis. Implants and surgical interventions have grown in popularity recently, and a number of these have been shown to have varying efficacy, including the minimally invasive lumbar decompression (MILD®), Vertiflex®, Coflex® Interlaminar Stabilization, and MinuteMan G3® procedures. Minimally invasive lumbar decompression (MILD®) is a minimally invasive outpatient procedure to treat spinal stenosis related to hypertrophied ligamentum flavum. The Superion® Interspinous Spacer, also known as Vertiflex®, is a titanium implant that is delivered percutaneously to relieve back pain caused by lumbar spinal stenosis. The MinuteMan® is a minimally invasive, interspinous-interlaminar fusion device planned for the temporary fixation of the thoracic, lumbar, and sacral spine, which eventually results in bony fusion. Based on our review of the available current scientific literature, the novel interventions for symptomatic lumbar spinal stenosis, such as the MILD® procedure and the Superion® interspinous spacer, generally appear to be safe and effective. There is a possibility in the future that these interventions could disrupt current treatment algorithms for lumbar spinal stenosis.

Pharmacological Advances in Opioid Therapy: A Review of the Role of Oliceridine in Pain Management.

Problems with the treatment of acute pain may arise when a patient is opioid-tolerant, such as those on chronic therapy with opioids or opiate replacement therapy, those who misuse opioids, and those who are in recovery. While some of the adverse effects of opioid medications are well known, it is also important to recognize the roles of tolerance and hyperalgesia. Oliceridine can target and modulate a novel µ-receptor pathway. The G protein-biased agonism of oliceridine allows for effective re-sensitization and desensitization of the mu-opioid receptor, which decreases the formation of opioid tolerance in patients. Oliceridine has been demonstrated to be an effective and relatively safe intravenous analgesic for the treatment of postoperative pain and is generally well tolerated with a favorable side effect profile when compared to morphine. As the prevalence of pain increases, it is becoming increasingly important to find safe and effective analgesics.

Peripheral Nerve Stimulation: A Review of Techniques and Clinical Efficacy.

Chronic pain is a common source of morbidity in many patient populations worldwide. There are growing concerns about the potential side effects of currently prescribed medications and a continued need for effective treatment. Related to these concerns, peripheral nerve stimulation has been regaining popularity as a potential treatment modality. Peripheral nerve stimulation components include helically coiled electrical leads, which direct an applied current to afferent neurons providing sensory innervation to the painful area. In theory, the applied current to the peripheral nerve will alter the large-diameter myelinated afferent nerve fibers, which interfere with the central processing of pain signals through small-diameter afferent fibers at the level of the spinal cord. Multiple studies have shown success in the use of peripheral nerve stimulation for acute post-surgical pain for orthopedic surgery, including post total knee arthroplasty and anterior cruciate ligament surgery, and chronic knee pain. Many studies have investigated the utility of peripheral nerve stimulation for the management of chronic shoulder pain. Peripheral nerve stimulation also serves as one of the potential non-pharmacologic therapies to treat back pain along with physical therapy, application of transcutaneous electrical neurostimulation unit, radiofrequency ablation, epidural steroid injections, permanently implanted neurostimulators, and surgery. Studies regarding back pain treatment have shown that peripheral nerve stimulation led to significant improvement in all pain and quality-of-life measures and a reduction in the use of opioids. Further studies are needed as the long-term risks and benefits of peripheral nerve stimulation have not been well studied as most information available on the effectiveness of peripheral nerve stimulation is based on shorter-term improvements in chronic pain.

A Comprehensive Review of Alternative Therapies for the Management of Chronic Pain Patients: Acupuncture, Tai Chi, Osteopathic Manipulative Medicine, and Chiropractic Care.

INTRODUCTION: Non-pharmacologic alternative therapies for pain have been around for a long time, some for hundreds of years. They have been used throughout history to treat many issues. RECENT FINDINGS: Currently, alternative medicine is most frequently used to treat musculoskeletal pain, and between 59 and 90% of patients utilizing alternative therapies for chronic pain claimed they were helpful and can serve as an effective adjunctive for the treatment of chronic pain. Some examples of alternative therapies that will be discussed in this review include acupuncture, tai chi, osteopathic manipulation, and chiropractic care. Acupuncture, traditionally a Chinese practice, is becoming more popular across the world to attempt to relieve pain. It involves the placement of thin needles at various points in the body. The efficacy of acupuncture for pain is heavily debated. More research and discussion are necessary to determine the exact role it plays in the treatment of chronic pain. Tai chi is also a traditional Chinese practice that is often used as a form of meditation and for potential health benefits. Tai chi involves a series of complex movements such as squatting combined with deep breathing to achieve relaxation and pain reduction. Osteopathic manipulative treatment (OMT) is a technique used by both osteopathic physicians (DO) as well as other health professionals to manage a wide range of conditions in any given patient. The technique involves utilization and manipulation of the musculoskeletal system to achieve potential health benefits. OMT has been used as therapy for many issues but is commonly used for pain conditions. Alternative therapies may serve as an effective adjunctive treatment modality for the management of chronic pain conditions. There has been a tremendous amount of research dictating the effectiveness of alternative therapies for chronic pain management. The purpose of this review is to provide a comprehensive evidence-based update of alternative therapy used for the management of chronic pain conditions.