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.

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.

Adjuvant Drugs for Peripheral Nerve Blocks: The Role of NMDA Antagonists, Neostigmine, Epinephrine, and Sodium Bicarbonate.

The potential for misuse, overdose, and chronic use has led researchers to look for other methods to decrease opioid consumption in patients with acute and chronic pain states. The use of peripheral nerve blocks for surgery has gained increasing popularity as it minimizes peripheral pain signals from the nociceptors of local tissue sustaining trauma and inflammation from surgery. The individualization of peripheral nerve blocks using adjuvant drugs has the potential to improve patient outcomes and reduce chronic pain. The major limitations of peripheral nerve blocks are their limited duration of action and dose-dependent adverse effects. Adjuvant drugs for peripheral nerve blocks show increasing potential as a solution for postoperative and chronic pain with their synergistic effects to increase the duration of action and decrease the required dosage of local anesthetic. N-methyl-d-aspartate (NMDA) receptor antagonists are a viable option for patients with opioid resistance and neuropathic pain due to their affinity to the neurotransmitter glutamate, which is released when patients experience a noxious stimulus. Neostigmine is a cholinesterase inhibitor that exerts its effect by competitively binding at the active site of acetylcholinesterase, which prevents the hydrolysis of acetylcholine and subsequently retaining acetylcholine at the nerve terminal. Epinephrine, also known as adrenaline, can potentially be used as an adjuvant to accelerate and prolong analgesic effects in digital nerve blocks. The theorized role of sodium bicarbonate in local anesthetic preparations is to increase the pH of the anesthetic. The resulting alkaline solution enables the anesthetic to more readily exist in its un-ionized form, which more efficiently crosses lipid membranes of peripheral nerves. However, more research is needed to show the efficacy of these adjuvants for nerve block prolongation as studies have been either mixed or have small sample sizes.

Novel Interventional Techniques for Chronic Pain with Minimally Invasive Arthrodesis of the Sacroiliac Joint: (INSITE, iFuse, Tricor, Rialto, and others).

Acute and chronic pain are public health issues that clinicians have been battling for years. Opioid medications have been a treatment option for both chronic and acute pain; however, they can cause unwanted complications and are a major contributor to our present opioid epidemic. The sacroiliac (SI) joint is a common cause of both acute and chronic low back pain. It affects about 15-25% of patients with axial low back pain, and up to 40% of patients with ongoing pain following lumbar fusion. Recent advances in the treatment of SI joint pain have led to the development of a wide variety of SI joint fusion devices. These fusion devices seek to stabilize the joints themselves in order that they become immobile and, in theory, can no longer be a source for pain. This is a minimally invasive procedure aimed to address chronic pain without subjecting patients to lengthy surgery or medications, including opioids with the potential for addiction and abuse. Minimally invasive SI fusion can be performed by a lateral approach (i.e., iFuse, Tricor) or posterior approach (i.e., CornerLoc, LinQ, Rialto). The posterior approach requires the patient to be in the prone position but allows for less disruption of muscles with entry. More data are necessary to determine which fusion system may be best for a particular patient. SI fusion devices are a promising way of treating chronic lower back pain related to the SI joint. This narrative review will discuss various types of SI fusion devices, and their potential use in terms of their safety and efficacy.

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.

Management of Lower Extremity Pain from Chronic Venous Insufficiency: A Comprehensive Review.

PURPOSE OF REVIEW: Chronic venous insufficiency is found to some extent in a large proportion of the world's population, especially in the elderly and obese. Despite its prevalence, little research has been pursued into this pathology when compared to similarly common conditions. Pain is often the presenting symptom of chronic venous insufficiency and has significant deleterious effects on quality of life. This manuscript will describe the development of pain in chronic venous insufficiency, and will also review both traditional methods of pain management and novel advances in both medical and surgical therapy for this disease. RECENT FINDINGS: Pain in chronic venous insufficiency is a common complication which remains poorly correlated in recent studies with the clinically observable extent of disease. Although lifestyle modification remains the foundation of treatment for pain associated with chronic venous sufficiency, compression devices and various pharmacologic agents have emerged as safe and effective treatments for pain in these patients. In patients for whom these measures are insufficient, recently developed minimally invasive vascular surgical techniques have been shown to reduce postsurgical complications and recovery time, although additional research is necessary to characterize long-term outcomes of these procedures. This review discusses the latest findings concerning the pathophysiology of pain in chronic venous insufficiency, conservative and medical management, and surgical strategies for pain relief, including minimally invasive treatment strategies.

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.

The role of regional anesthesia in the propagation of cancer: A comprehensive review.

New cancer incidences worldwide will eclipse 18 million in 2019, with nearly 10 million cancer-related deaths. It is estimated that in the United States, almost 40% of individuals will be diagnosed with cancer in their lifetime. Surgical resection of primary tumors remains a cornerstone of cancer treatment; however, the surgical process can trigger an immune-suppressing sympathetic response, which promotes tumor growth of any residual cancerous cells post surgery. Regional and local anesthesia have become staples of anesthesia and analgesia during and after surgery. Recently, much evidence in the form of retrospective and prospective studies has come to light regarding the protective, antitumor properties of anesthetic and analgesic agents across a wide variety of cancers and patient demographics. It is believed that by blocking afferent pain signals, the body does not mount the sympathetic response that contributes to the perpetuation of disease after surgical treatment. This review, therefore, investigates these studies as they pertain to the treatment and outcomes of cancers treated surgically to elucidate the role of regional anesthesia in the propagation of cancer.

PECS, serratus plane, erector spinae, and paravertebral blocks: A comprehensive review.

Thoracic planar blocks represent a novel and rapidly expanding facet of regional anesthesia. These recently described techniques represent the potential for excellent analgesia, enhanced technical safety profiles, and reduced physiological side effects versus traditional techniques in thoracic anesthesia. Regional techniques, particularly those described in this review, have potential implications for mitigation of surgical pathophysiological neurohumoral changes. In the present investigation, we describe the history, common indications, technique, and limitations of pectoral nerves (PECS), serratus plane, erector spinae plane, and thoracic paravertebral plane blocks. In summary, these techniques provide excellent analgesia and merit consideration in thoracic surgery.

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.

Geriatric pain management, pharmacological and nonpharmacological considerations

Persistent pain is prevalent in the elderly population, although it is not an inevitable part of aging. It is important to understand how to manage pain effectively in old age, particularly because an increasing number of individuals are becoming older, or living longer. Several problems, less common in younger adults, may complicate the treatment of pain. An accurate pain assessment is required for the most efficient strategy of pain treatment. Challenges to an effective pain assessment include: pain underreporting by patients, atypical manifestations of pain in elderly, age-associated pharmacodynamic and pharmacokinetic changes to specific drugs, other general age-related changes, and misconceptions about tolerance or addiction to opioids. However, physicians are able to provide geriatric patients with appropriate analgesia by using comprehensive assessment involving a multidisciplinary approach, and the appropriate use of various treatment modalities.

Perioperative management of neurofibromatosis type 1.

Neurofibromatosis type 1 (neurofibromatosis-1), a relatively common single-gene disorder, is caused by a mutation of the NF1 gene that results in a loss of activity or in a nonfunctional neurofibromin protein. Clinical anesthesiologists may find patients with neurofibromatosis-1 challenging because this condition may affect most organ systems and result in a wide variety of presentations and clinical implications. Current neurofibromatosis-1 research studies include genotype-phenotype correlations, investigation of the pathoetiology behind the different clinical manifestations of neurofibromatosis-1, and the search for treatment options for the different features of the disorder. Neurofibromatosis-1-associated complications of the central nervous, respiratory, cardiovascular, musculoskeletal, and gastrointestinal and genitourinary systems all present various degrees of considerations for anesthesiologists. Additionally, neurofibromatosis-1 has dramatic implications for pregnant women.

Arteriovenous malformation, complications, and perioperative anesthetic management.

Arteriovenous malformations (AVMs) are the most common intracranial vascular malformation, with an estimated occurrence of 1:5000-1:2000 persons. The repair requires careful embolization, often followed by stereotactic radiosurgery and can also include open craniotomy. Preoperatively, patients may be healthy or dramatically unstable, as 30-50% of these cases present with acute cerebral hemorrhage. One of the most important considerations for the anesthesiologist should be attempting to achieve hemodynamic stability in the face of potential increased intracranial pressure and subsequent vulnerability of the tissues to ischemic insult. Knowledge of the risks and hazards of the procedure and collaboration with specialists, including neuroradiologists, critical care physicians, and potentially neurosurgeons, ultimately form the basis for appropriate management. AVM's can lead to potentially fatal ischemic or hemorrhagic complications that may occur in up to 8% of cases. The protection of the airway, adequate monitoring, and maintaining cardiovascular and neurological stability, are critical. Further, in the setting of a radiological suite, peripheral location considerations involving equipment, monitors, and appropriate drugs and sustaining the patient's immobility during the radiological procedures, while managing potential perioperative complications are all essential.

Pharmacology of cyclooxygenase-2 inhibitors and preemptive analgesia in acute pain management.

PURPOSE OF REVIEW: NSAIDs have served as analgesic, antiinflammatory, and antipyretic medicines for over a century. A novel class of NSAIDs, cyclooxygenase-2 inhibitors, was introduced in 1999. All NSAIDs and aspirin inhibit active sites of cyclooxygenase-1 and cyclooxygenase-2. Recent studies have demonstrated an important role of cyclooxygenase-2 inhibitors in the management of acute pain processes. RECENT FINDINGS: There have been many reports related to an 'imbalance theory' suggesting that cyclooxygenase-2 inhibitors create an 'imbalance' between thromboxane and prostacyclin (reduction of prostacyclin), resulting in a prothrombic state; however, these drugs were designed to have improved gastrointestinal safety profiles by being more selective of the cyclooxygenase-2 pathway. Although balance and regulation of hemostasis is influenced in part by the balance of prostacyclin and thromboxane A2, many other substances are involved in thrombosis and include the coagulation cascade, fibrinogen and plasminogen pathways, numerous endogenous substances such as adenosine, nitric oxide, and serotonin. SUMMARY: On the basis of many human studies, one may conclude that perioperative cyclooxygenase-2 inhibitors, in standard doses, decrease opioid consumption. Future investigations that include different multimodal techniques, for example combining cyclooxygenase-2 inhibitors with regional blocks, may help elucidate and clarify the true benefits of perioperative cyclooxygenase-2 inhibitors in acute pain management strategies.