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Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States.

Opioid use disorder is a well-established and growing problem in the United States. It is responsible for both psychosocial and physical damage to the affected individuals with a significant mortality rate. Given both the medical and non-medical consequences of this epidemic, it is important to understand the current treatments and approaches to opioid use disorder and acute opioid overdose. Naloxone is a competitive mu-opioid receptor antagonist that is used for the reversal of opioid intoxication. When given intravenously, naloxone has an onset of action of approximately 2 min with a duration of action of 60–90 min. Related to its empirical dosing and short duration of action, frequent monitoring of the patient is required so that the effects of opioid toxicity, namely respiratory depression, do not return to wreak havoc. Nalmefene is a pure opioid antagonist structurally similar to naltrexone that can serve as an alternative antidote for reversing respiratory depression associated with acute opioid overdose. Nalmefene is also known as 6-methylene naltrexone. Its main features of interest are its prolonged duration of action that surpasses most opioids and its ability to serve as an antidote for acute opioid overdose. This can be pivotal in reducing healthcare costs, increasing patient satisfaction, and redistributing the time that healthcare staff spend monitoring opioid overdose patients given naloxone.

Coronavirus disease (COVID-19) causes many deleterious effects throughout the body. Prior studies show that the incidence of acute kidney injury in COVID-19 patients could be as high as 25%. There are also autopsy reports showing evidence of viral tropism to the renal system. In this regard, COVID-19 can damage the kidneys and increase a patient's risk of requiring dialysis. Available evidence suggests that renal involvement in COVID-19 infection is not uncommon, and there has been an increased incidence of chronic kidney disease related to the pandemic. In this literature analysis, we address COVID-19 and its effects on the renal system, including the pathophysiologic mechanisms. We also address current studies on the causes of injury to the renal system, the cause of kidney failure, its effect on mortality, the impact on dialysis patients, and the impact on renal transplant patients. COVID-19 disease may have unique features in individuals on chronic dialysis and kidney transplant recipients, requiring increased vigilance in limiting viral transmission in perioperative, in-patient, and dialysis center settings.

The Hospital Incident Command System (HICS) is an incident management system specific to hospitals based on the principles of Incident Command System (ICS), and it includes prevention, protection, mitigation, response, and recovery. It plays a crucial role in effective and timely response during the periods of disasters, mass casualties, and public health emergencies. In recent times, hospitals have used a customized HICS structure to coordinate effective responses to public health problems such as the Ebola outbreak in the US and SARS epidemic in Taiwan. The current COVID-19 pandemic has placed unprecedented challenges on the healthcare system, necessitating the creation of HICS that can help in the proper allocation of resources and ineffective utilization of healthcare personnel. The key elements in managing a response to this pandemic include screening and early diagnosis, quarantining affected individuals, monitoring disease progression, delivering appropriate treatment, and ensuring an adequate supply of personal protective equipment (PPE) to healthcare staff.

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.

Psychosis, a break in reality which is manifested as hallucinations, delusions or the disruption in thought process, is the hallmark of schizophrenia. Despite novel pharmacotherapy advancements of antipsychotic medications that have resulted in some patients having the ability to return to social settings and thereby decreasing psychotic symptoms and reducing hospital admissions, there is still a sub-population of patients who remain symptomatic. Treatment-resistant schizophrenia is defined as failure of treatment with at least two different antipsychotics with the proper length of treatment and titration. Clozapine has been heralded as a drug to resolve the puzzle of treatment-resistant schizophrenia. Clozapine has one side effect that is well known, being the development of agranulocytosis. However, there is another side effect that can limit clozapine’s use and can also be life-threatening. Recently, at the end of January 2020, the FDA issued a communications statement which “[strengthened] an existing warning that constipation caused by the schizophrenia medicine clozapine can, uncommonly, progress to serious bowel complications.” After identifying ten cases of constipation from between 2006 to 2016 that progressed to hospitalization, surgery, and even death, the FDA focused their attention on this often overlooked, common side effect, especially when considering the strong anticholinergic effects of clozapine. Although patients are screened by their physicians for agranulocytosis by weekly lab monitoring, constipation is also a complication that needs to be identified and treated. Much like opioid-induced constipation, constipation can also be reduced with the use of laxatives and reduction in the co-prescribing of anticholinergic therapies with clozapine.

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.

Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18–24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk–benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs.

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.

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.

Keratoconjunctivitis sicca (“dry eye”) is a common (14%–30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as “burning eye syndrome.” This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome. Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment centers around symptomatic alleviation and reduction of inflammation. Conservative treatments focus on well-being and perception and include exercise, acupuncture, and cognitive behavioral therapy. Topical treatment consists of the anti-adhesion T-cell antagonist lifitegrast, corticosteroids, and cyclosporine; all have moderate efficacy and good safety. Autologous serum eye drops are a second-line topical that may promote corneal and neural healing on top of symptomatic relief. When these treatments fail, patients may trial neuromodulation with transcranial magnetic stimulation. Despite general treatment safety, more research is needed to develop novel approaches to this condition, possibly focusing more directly on the neurological component.

HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine (sodium-channel blocker) and low-dose meloxicam (non-steroidal anti-inflammatory drug [NSAID]) applied needle-free during surgery. Introducing low-dose meloxicam addresses the limited efficacy of liposomal bupivacaine in acidic inflamed tissues and allows enhanced analgesic effects over three days. It has great promise to be an extremely effective postoperative pain regimen and produce an opioid-free surgical recovery, as it has consistently significantly reduced pain scores and opioid consumption through 72 h. This manuscript provides an updated, concise narrative review of the pharmacology, clinical efficacy, safety and tolerability of this drug and its applications to prevent postoperative pain.Lay abstract HTX-011 is a local anesthetic (a drug to induce temporary loss of sensation or awareness, usually during a medical procedure), which is made up of a combination of two drugs and applied needle-free during surgery. It has great promise to provide effective treatment for postoperative pain (pain after an operation), allowing patients to have an opioid-free option for their pain relief. This paper reviews how this drug works and the clinical trials that have taken place so far to investigate its safety and effectiveness in reducing pain after an operation.

Purpose of Review. This is a comprehensive review of the literature regarding the use of Aripiprazole lauroxil for schizophrenia. This review presents the background, evidence, and indications for using aripiprazole lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. Recent Findings. Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D2 and 5-HT1A receptors combined with antagonist activity at 5-HT2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole lauroxil was FDA approved in October of 2015. Summary. Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, aripiprazole lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective.

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient’s quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events.

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies—including antibody therapy and oral agents—were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS.

Cancer is now a leading health concern worldwide. In an effort to provide these patients with adequate care, coordination between anesthesiologists and surgeons is crucial. In cancer-related treatment, it is very clear that radio-chemotherapy and medical procedures are important. There are some obstacles to anesthesia when dealing with cancer treatment, such as physiological disturbances, tumor-related symptoms, and toxicity in traditional chemotherapy treatment. Therefore, it is important that a multisystemic, multidisciplinary and patient-centered approach is used to preserve perioperative homeostasis and immune function integrity. Adding adjuvants can help increase patient safety and satisfaction and improve clinical efficacy. Correctly paired anesthetic procedures and medications will reduce perioperative inflammatory and immune changes that could potentially contribute to improved results for future cancer patients. Further research into best practice strategies is required which will help to enhance the acute and long-term effects of cancer care in clinical practice.

Introduction The multifaceted clinical presentation of fibromyalgia (FM) supports the modern understanding of the disorder as a more global condition than one simply affecting pain sensation. The main pharmacologic therapies used clinically include anti-epileptics and anti-depressants. Conservative treatment options include exercise, myofascial release, psychotherapy, and nutrient supplementation. Methods Narrative review. Results Nutrient supplementation is a broadly investigated treatment modality as numerous deficiencies have been linked to FM. Additionally, a proposed link between gut microbiome patterns and chronic pain syndromes has led to studies investigating probiotics as a possible treatment. Despite positive results, much of the current evidence regarding this topic is of poor quality, with variable study designs, limited sample sizes, and lack of control groups. Conclusions The etiology of FM is complex, and has shown to be multi-factorial with genetics and environmental exposures lending influence into its development. Preliminary results are promising, however, much of the existing evidence regarding diet supplementation is of poor quality. Further, more robust studies are needed to fully elucidate the potential of this alternative therapeutic option.

Valtoco® is a new FDA-approved nasal spray version of diazepam indicated for the treatment of acute, intermittent, and stereotypic episodes of frequent seizure activity in epilepsy patients six years of age and older. Although IV and rectal diazepam are already used to treat seizure clusters, Valtoco® has less variability in plasma concentration compared to rectal diazepam. Furthermore, the intranasal administration of Valtoco® is more convenient and less invasive than rectal or IV diazepam, making it ideal for self-administration outside of a hospital setting. Multiple clinical trials have taken place comparing Valtoco® to the oral, rectal, and IV forms of diazepam. Aside from mild nasal irritation and lacrimation, Valtoco® was found to have no increased safety risk in comparison to traditional forms of diazepam. This review of Valtoco® will include a history of diazepam prescribing and withdrawal treatment, Valtoco® drug information, its mechanism of action, pharmacokinetics and pharmacodynamics, and a comprehensive review of clinical studies.

Background: Patients who are diagnosed with dextrocardia, a rare congenital heart condition in which the heart points toward the right side of the chest, need their specific situs classification (eg, solitus, inversus, ambiguus) ascertained to optimize their care and outcomes. In this report, we discuss the perioperative anesthetic management of a patient presenting with dextrocardia. Case Report: A 44-year-old African American female with a history of hypertension, hyperlipidemia, gastroesophageal reflux disease, and diabetes mellitus type 2 was admitted for shortness of breath, dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea. The patient had been diagnosed with dextrocardia in 2003 at an outside hospital and was asymptomatic prior to this presentation. Chest x-ray revealed bilateral perihilar vascular congestion with bibasilar atelectasis and suspected small bilateral pleural effusions consistent with new-onset congestive heart failure. Preoperative 2-dimensional transthoracic echocardiography revealed an ostium secundum–type atrial septal defect (ASD) with mild left-to-right atrial shunting. The patient's ASD was repaired using a pericardial patch. Conclusion: The anesthetic management of patients presenting with dextrocardia is complex. Preoperative cardiac transthoracic echocardiography can identify cardiac lesions or aberrant anatomy associated with dextrocardia. Proper placement of electrocardiogram electrodes is necessary to avoid false-positive results for perioperative ischemia. Central line access must be adjusted to anatomic variations. Clinicians should have high suspicion for associated pulmonary hypertension and should limit sedatives preoperatively to minimize the cardiovascular effects of hypoxia and/or hypercarbia on the pulmonary vasculature. Finally, high clinical suspicion for respiratory complications should be maintained, as dextrocardia has been associated with respiratory complications secondary to primary ciliary dyskinesia in approximately 25% of patients.

Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.

Parkinson’s disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and disability. PD is caused by a loss of dopaminergic, cholinergic, serotonergic, and noradrenergic neurons in the central nervous system (CNS), and peripherally; the syndromic parkinsonism symptoms of movement disorder, gait disorder, rigidity and tremor are mostly driven by the loss of these neurons in the basal ganglia. Unfortunately, a significant proportion of patients taking levodopa, the standard of care treatment for PD, will begin to experience a decrease in effectiveness at varying times. These periods, referred to as “off episodes”, are characterized by increased symptoms and have a detrimental effect on quality of life and disability. Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa/carbidopa in patients experiencing “off episodes”. It promotes dopaminergic activity by antagonizing adenosine in the basal ganglia. This review will discuss istradefylline as a treatment for PD patients with off episodes.

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

Hospitals face catastrophic financial challenges in light of the coronavirus disease 2019 (COVID-19) pandemic. Acute shortages in materials such as masks, ventilators, intensive care unit capacity, and personal protective equipment (PPE) are a significant concern. The future success of supply chain management involves increasing the transparency of where our raw materials are sourced, diversifying of our product resources, and improving our technology that is able to predict potential shortages. It is also important to develop a proactive budgeting strategy to meet supply demands through early designation of dependable roles to support organizations and through the education of healthcare staff. In this paper, we discuss supply chain management, governance and financing, emergency protocols, including emergency procurement and supply chain, supply chain gaps and how to address them, and the importance of communication in the times of crisis.

Purpose of Review This is a comprehensive review of the current literature on the usage of galcanezumab for migraine treatment. It reviews the biology, pathophysiology, epidemiology, diagnosis, and conventional treatment of migraines, then compares the literature available for galcanezumab with historical treatment options. Recent Findings Migraine is a common headache disorder and constitutes a significant source of distress from both a personal and societal perspective. Conventional treatment includes abortive and preventive treatment. Treatment options are limited and may be only partially or minimally effective in some of the population. Recent evidence points to metabolic changes in the brain as possible causes of migraine, via reduced available energy or a spiking need for it, resulting in a relative insufficiency. This leads to trigeminocervical complex (TCC) activation and a headache episode, modulated by calcitonin gene-related peptide (CGRP). Galcanezumab (Emgality) is a monoclonal antibody targeting CGRP that is given in a monthly injection for the prevention of migraines. Its safety was previously shown in phase 1 and 2 trials, and recent phase 3 trials showed efficacy, with up to 50% reduction in monthly migraine days and improved functional capacity in migraineurs. Studies show that the drug is well tolerated and safe. Summary Migraine headache is a common neurological syndrome that causes great pain and suffering. Treatment options today are limited. Galcanezumab does not prevent migraines, but it is effective in decreasing their frequency and length. It is also much better tolerated than the currently existing therapies. While it is unlikely to provide monotherapy for migraines, it is a novel therapy that may be added for cases of severe or frequent migraines.

Acupuncture is a form of traditional Chinese medicine that is performed by placing needles or pressure in specific locations on a patient’s skin to achieve a therapeutic effect. Although used to treat a variety of disorders, one of the most common applications of acupuncture is to treat chronic pain, especially headache and migraine pain. Migraines are difficult to treat, and pharmacotherapies are often the first line of treatment, although these options have many unwanted side effects, such as exacerbation of headache pain in those with chronic migraine. Many complimentary and integrative therapies are available to treat migraine (including nutraceuticals, yoga, tai chi, and biofeedback), among which acupuncture as a treatment is gaining increasing attention. In this review, we provide an overview of the current understanding of both acupuncture and migraine and of current research investigating the effectiveness of acupuncture in treating migraine and chronic migraine.

Myofascial Pain Syndrome (MPS) is a regional pain disorder that affects every age-group and is characterized by the presence of trigger points (TrPs) within muscles or fascia. MPS is typically diagnosed via physical exam, and the general agreement for diagnostic criteria includes the presence of TrPs, pain upon palpation, a referred pain pattern, and a local twitch response. The prevalence of MPS among patients presenting to medical clinics due to pain ranges anywhere from 30 to 93%. This may be due to the lack of clear criteria and guidelines in diagnosing MPS. Despite the prevalence of MPS, its pathophysiology remains incompletely understood. There are many different ways to manage and treat MPS. Some include exercise, TrP injections, medications, and other alternative therapies. More research is needed to form uniformly-accepted diagnostic criteria and treatments.

Pharmacogenomics is the study of how genetic differences between individuals affect pharmacokinetics and pharmacodynamics. These differences are apparent to clinicians when taking into account the wide range of responses to medications given in clinical practice. A review of literature involving pharmacogenomics and pain management was performed. The implementation of preoperative pharmacogenomics will allow us to better care for our patients by delivering personalized, safer medicine. This review describes the current state of pharmacogenomics as it relates to many aspects of clinical practice and how clinicians can use these tools to improve patient outcomes.

Lateral epicondylitis (LE), also known as tennis elbow, is the most common cause of elbow pain in adults, with approximately 1-3% of the general population being afflicted. Although the condition is usually self-limiting, pain can be a major hindrance, limiting daily activity and the work capacity of patients. As a result, many treatment options have become available with the aim to shorten the duration of the disease and increase the quality of life. Steroid injections, NSAIDs, topical creams, platelet-rich plasma, physical therapy, and kinesiotaping are considered conservative treatments, while surgical options are last-resort treatments reserved for refractory LE. In this review, we will provide a brief summary of LE and focus on addressing conservative and minimally invasive interventional options for the treatment of LE.

Introduction Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5–5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. Methods A literature review of folic acid supplementation for various disease states including cardiovascular disease was conducted. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. Results In this review, we discuss the biochemistry of folic acid, Hcy biosynthesis, Hcy and hydrogen sulfide bioavailability, pathogenesis of hyperhomocysteinemia and its role as a risk factor for disease, and treatment studies with folic acid supplementation in disease states. Conclusion Folic acid supplementation should be recommended to any patient who has an elevated Hcy level, and this level should be measured and treated at an early age, since folic acid is easily obtained and may likely reduce vascular disease and other deleterious pathologic processes in high-risk populations.

Platelet diseases and dysfunction are taught early in medical school to all future physicians. Understanding of the coagulation cascade and hemostatic mechanisms has allowed for targeted pharmacological therapies that have been significantly impactful in clinical practice. Platelets are an early participant in hemostasis physiologically and under pathophysiological states. A review of literature involving platelet disfunction. Various presentations of platelet diseases and dysfunction challenge clinicians and require a firm understanding of normal platelet function, drugs that mediate or modulate platelet effectiveness, and nonpharmacologic etiologies of platelet diseases and dysfunction with corresponding best practice treatment approaches. This review summarizes normal and abnormal states associated with platelets and treatment strategies.

Important elements of the preoperative assessment that should be addressed for the older adult population include frailty, comorbidities, nutritional status, cognition, and medications. Frailty has emerged as a plausible predictor of adverse outcomes after surgery. It is present in older patients and is characterized by multisystem physiologic decline, increased vulnerability to stressors, and adverse clinical outcomes. Preoperative preparation may include a prehabilitation program, which aims to address nutritional insufficiencies, modify chronic polypharmacy, and enhance physical and respiratory conditions prior to hospital admission. Special considerations are taken for particularly high-risk patients, where the approach to prehabilitation can address specific, individual risk factors. Identifying patients who are nutritionally deficient allows practitioners to intervene preoperatively to optimize their nutritional status, and different strategies are available, such as immunonutrition. Previous studies have shown an association between increased frailty and the risk of postoperative complications, morbidity, hospital length of stay, and 30-day and long-term mortality following general surgical procedures. Evidence from numerous studies suggests a potential benefit of including a standard assessment of frailty as part of the preoperative workup of older adult patients. Studies addressing validated frailty assessments and the quantification of their predictive capabilities in various surgeries are warranted.

The management principles of non-obstetric surgery during pregnancy are important concepts for all health care providers to be cognizant of. The goals of non-obstetric surgery are to ensure maternal safety, maintain the pregnancy, and ensure fetal well-being. In this regard, organogenesis occurs roughly between days 7-57 and thus, certain medications have a higher incidence of fetal teratogenicity in this first trimester. Some examples of common surgeries performed urgently or emergently include appendectomies, ovarian detorsions, bowel obstruction, trauma, and cholecystectomies. The choice of anesthetic technique and the selection of appropriate anesthetic drugs should be guided by indication for surgery, the nature of the surgery, and the site of the surgical procedure. Many of the concerns for any patients undergoing urgent or emergent surgery must be considered by anesthesia providers along with steps to ensure the fetus has the best outcome.

Preoperative laboratory testing is often necessary and can be invaluable for diagnosis, assessment, and treatment. However, performing routine laboratory tests for patients who are considered otherwise healthy is not usually beneficial and is costly. It is estimated that $18 billion (U.S.) is spent annually on preoperative testing, although how much is wasteful remains unknown. Ideally, a targeted and comprehensive patient history and physical exam should largely determine whether preprocedure laboratory studies should be obtained. Healthcare providers, primarily anesthesiologists, should remain cost-conscious when ordering specific laboratory or imaging tests prior to surgery based on available literature. We review the overall evidence and key points from the Choosing Wisely guidelines, the identification of potential wasteful practices, possible harms of testing, and key clinical findings associated with preoperative laboratory testing.

Postoperative pulmonary complications (PPCs), estimated between 2.0% and 5.6% in the general surgical population and 20-70% for upper abdominal and thoracic surgeries, are a significant factor leading to poor patient outcomes. Efforts to decrease the incidence of PPCs such as bronchospasm, atelectasis, exacerbations of underlying chronic lung conditions, infections (bronchitis and pneumonia), prolonged mechanical ventilation, and respiratory failure, begins with a detailed preoperative risk evaluation. There are several available preoperative tests to estimate the risk of PPCs. However, the value of some of these studies to estimate PPCs remains controversial and is still debated. In this review, the preoperative risk assessment of PPCs is examined along with preoperative pulmonary tests to estimate risk, intraoperative, and procedure-associated risk factors for PPCs, and perioperative strategies to decrease PPCs. The importance of minimizing these events is reflected in the fact that nearly 25% of postoperative deaths occurring in the first week after surgery are associated with PPCs. This review provides important information to help clinical anesthesiologists to recognize potential risks for pulmonary complications and allows strategies to create an appropriate perioperative plan for patients.

Purpose of Review This is a comprehensive review of the literature about the use of bupivacaine hydrochloride for the treatment of post-herpetic neuralgia (PHN). It briefly reviews the background, biology, diagnosis and conventional treatment for PHN, and then introduces and compares the recent evidence for the use of topical bupivacaine. Recent Findings PHN is defined by pain lasting 90 days or more after the initial presentation of herpes zoster (“Shingles”, HZ) rash and is the most common complication of this disease. A product of re-activation of the Varicella-Zoster virus (VZV), HZ is diagnosed more than 1 million times annually in the United States. Approximately 20% of patients with HZ will experience PHN and will continue to suffer intermittent neuropathic symptoms, including itching and pain, that is sharp, stabbing, throbbing or burning, with the pain localized to the site of their original rash. This long-lasting pain compares with the severity of long-standing rheumatics and osteo-arthritis and is accompanied by severe allodynia causing significant suffering, and a financial burden that is manifested in both healthcare costs and loss of quality-adjusted life years. Prevention of PHN may be achieved with the Zoster vaccine, although there is still a large segment of unvaccinated population. Moreover, the Zoster vaccine is not always effective for prevention. Current treatment includes medical (systemic tricyclic antidepressants, anticonvulsants and opioids, topical lidocaine and capsaicin) and interventional (subcutaneous Botox injections, nerve blocks and nerve stimulation) therapies. These therapies are not always effective, and each carries their own profile of side effects and risks. Moreover, up to 50% of patients with PHN are refractory to management. Recent evidence is emerging to support the use of topical local anesthetics for the treatment of PHN. Two small studies recently found topical lidocaine spray to be effective in treating paroxysmal pain attacks associated with PHN. Bupivacaine is a longer-lasting local anesthetic, and a film-forming formulation allows easy and durable application to the affected skin. Recent studies show that topical film-forming bupivacaine is safe and as effective as lidocaine for the treatment of PHN. Summary PHN is an important though common complication of HZ and can cause long-lasting pain and disability. Current treatment for PNH is limited by efficacy and safety profiles of individual therapies. Recent evidence points to topical local anesthetics as an effective and safe alternative to conventional therapy. Film-forming bupivacaine may offer a durable and safe option for this otherwise difficult to treat syndrome.

Purpose This is a comprehensive review of the current literature on central neuropathic pain mechanisms that is secondary to spinal cord injury. It reviews recent and seminal findings on the pathophysiology, diagnosis, and treatment and compares treatment options and recommendations. Recent Findings Neuropathic pain (NP) is a common complication of spinal cord injury (SCI). Chronicity of NP is attributed to increased abundance of inflammatory mediators and ion channel dysfunction leading to afferent nerve sensitization; nerve damage and nerve–glia cross talk have also been implicated. Conventional treatment is medical and has had limited success. Recent studies have made headway in identifying novel biomarkers, including microRNA and psychosocial attributes that can predict progress from SCI to chronic NP (CNP). Recent advances have provided evidence of efficacy for two promising drugs. Baclofen was able to provide good, long-lasting pain relief. Ziconotide, a voltage-gated calcium channel blocker, was studied in a small trial and was able to provide good analgesia in most participants. However, several participants had to be withdrawn because of worrisome creatine phosphokinase (CPK) elevations, and further studies are required to define its safety profile. Non-medical interventions include brain sensitization and biofeedback techniques. These methods have recently had encouraging results, albeit preliminary. Case reports of non-conventional techniques, such as hypnosis, were also reported. Summary CNP is a common complication of SCI and is a prevalent disorder with significant morbidity and disability. Conventional medical treatment is limited in efficacy. Recent studies identified baclofen and ziconotide as possible new therapies, alongside non-medical interventions. Further research into the pathophysiology is required to identify further therapy candidates. A multidisciplinary approach, including psychosocial support, medical and non-medical interventions, is likely needed to achieve therapeutic effects in this difficult to treat syndrome.

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.

Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hyponatremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications—it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotransmission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia.

Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.

The objectives of this review are to describe the acquired and hereditary causes of methemoglobinemia, to recommend the most sensitive diagnostic tests, and to enable critical care clinicians to rapidly detect and treat methemoglobinemia. To meet these objectives, Internet search engines were queried with the keywords to select articles for review that included case reports, case series, observational, longitudinal, and surveillance studies. The most common causes of methemoglobinemia include oxidizing reactions to cocaine-derived anesthetics, such as benzocaine and lidocaine, to antibiotics, such as dapsone and other sulfonamides, and to gases, such as nitric oxide. Additionally, CO-oximetry is superior to standard pulse oximetry in detecting methemoglobinemia. Finally, effective treatments for methemoglobinemia include intravenous administration of methylene blue, ascorbic acid, and riboflavin. In this manuscript we will discuss methemoglobinemia, how it occurs, and how to treat it.

Surgeries and chronic pain states of the upper extremity are quite common and pose unique challenges for the clinical anesthesiology and pain specialists. Most innervation of the upper extremity involves the brachial plexus. The four most common brachial plexus blocks performed in clinical setting include the interscalene, supraclavicular, infraclavicular, and axillary brachial plexus blocks. These blocks are most commonly performed with the use of ultrasound-guided techniques, whereby analgesia is achieved by anesthetizing the brachial plexus at different levels such as the roots, divisions, cords, and branches. Additional regional anesthetic techniques for upper extremity surgery include wrist, intercostobrachial, and digital nerve blocks, which are most frequently performed using landmark anatomical techniques. This review provides a comprehensive summary of each of these blocks including anatomy, best practice techniques, and potential complications.

Kratom, or Mitragyna, is a tropical plant indigenous to Southeast Asia, with unique pharmacological properties. It is commonly consumed by preparing the leaves into decoction or tea, or by grinding them into a powder. Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria, as well as stimulant properties, which together raise potential concern for dependence and addiction. Moreover, growing evidence suggests that the prevalence of kratom use is increasing in many parts of the world, raising important considerations for healthcare providers. This manuscript will discuss the most current epidemiology, pharmacology, toxicity, and management related to kratom, while seeking to provide a contemporary perspective on the issue and its role in the greater context of the opioid epidemic.

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.

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.

Pain is a significant consequence of cardiac surgery and newer techniques in cardiac anesthesia have provided an impetus for the development of multimodal techniques to manage acute pain in this setting. In this regard, regional anesthesia techniques have been increasingly used in many cardiac surgical procedures, for the purposes of reducing perioperative consumption of opioid agents and enhanced recovery after surgery. The present investigation focuses on most currently used regional techniques in cardiac surgical procedures. These regional techniques include chest wall blocks (e.g., PECS I and II, SAP, ESB, PVB), sternal blocks (e.g., TTMPB, PSINB), and neuraxial blocks (e.g., TEA, high spinal anesthesia). The present investigation also summarizes indications, technique, complications, and potential clinical benefits of these evolving regional techniques. Cardiac surgery patients may benefit from application of these regional techniques with well controlled indications and careful patient selections.

Novel preparations allowing for the extended duration of action of local anesthetics have many clinically relevant benefits. With regard to this, the development of liposomal bupivacaine has the potential to significantly impact patient care by improving perioperative pain control. The unique liposomal bilayer that encapsulates bupivacaine allows for a sustained release of local anesthetic for up to 72 h after a single use and can significantly decrease postoperative opioid consumption. SABER-bupivacaine is another depot formulation that helps in sustained release of bupivacaine from an encapsulated bupivacaine in a biodegradable sucrose acetate isobutyrate biolayer. HTX-011 is an investigational extended-release local anesthetic formulation currently undergoing Phase 3 clinical trials. HTX-011 is composed of a bioerodible polymer with bupivacaine and low-dose meloxicam in which the polymer undergoes hydrolysis and allows for sustained release of bupivacaine and meloxicam for 3 days. The present investigation reviews pharmacologic considerations related to the formulation of liposomal bupivacaine, current FDA-approved indications for its use, and future extended-release local anesthetic formulations currently under investigation.

Regional anesthesia has evolved as an important tool for anesthesiologists and surgeons managing patients for surgery of the head and neck region. In recent years, ultrasound use has increased significantly, and newer nerve blocks have been established for surgeries of the head and regions. In this review, anatomy, indications, efficacy, and potential side effects of regional anesthesia for the head and neck region are presented. Evolving practice strongly suggests that regional nerve blocks for the head and neck region are safe and effective. Future studies and education will likely evolve practice to make these regional techniques standards for future surgeries of the head and neck region.

Diagnostic ultrasonography was first utilized in the 1940s. The past 70+ years have seen an explosion in both ultrasound technology and availability of ultrasound technology to more and more clinicians. As ultrasound technology and availability have grown, the utility of ultrasound technology in the clinical setting as only been limited by clinicians' imagination. Due to its lack of radiation, non-invasive nature, and gentle learning curve, medical ultrasonography is now a tremendously useful Point of Care technology in the clinical arena. What follows is a discussion of Point of Care Ultrasound (PoCUS) and how it can be incorporated in the daily practice of any regional anesthesiology. While most regional anesthesiologists usually focus on the interventional aspects of ultrasonography (i.e. nerve blocks), our discussion will center on the diagnostic value of ultrasonography-especially concerning assessment of cardiac physiology and pathophysiology, gastric anatomy, airway anatomy, and intracranial pathophysiology. After reading and reviewing this chapter, the learner will have the knowledge to start training themselves in a variety of PoCUS exams that will allow rapid diagnosis of normal and abnormal patient conditions. Once an accurate diagnosis is established, the anesthesiologist and his/her team can then confidently optimize an anesthetic pain, prevent harm, and/or treat a patient condition. In this day and age, the ability to rapidly establish an accurate diagnosis cannot be overstated-especially in a critical situation. It is the authors' sincerest hope that the following discussion will help regional anesthesiologist to become even better and well-rounded clinical leaders.

Background Pulmonary arterial hypertension is a hemodynamic disorder. Signs and symptoms are generally difficult to recognize because they are non-specific. The current treatment for pulmonary arterial hypertension offers no cure or prevention; therefore, it is important to explore treatment avenues for novel pulmonary arterial hypertension treatments. In this study, we tested the hypothesis: pulmonary vasodilator responses of adenosine are dependent on the activation of l-type calcium channels, independent of the synthesis of nitric oxide from l-arginine, activation of adenosine triphosphate-sensitive potassium channels, and the release of cyclooxygenase products. Methods We performed an isolated lobar lung preparation in mongrel cats. The thromboxane A2 analog U-46619 was used to increase lobar arterial pressure to a high steady level. We recorded responses to adenosine and other vasodepressor agents in the pulmonary vascular bed of a cat under conditions of controlled pulmonary blood flow and constant left atrial pressure. Results These data show that adenosine has significant vasodepressor activity in the pulmonary vascular bed of the cat. The data suggest that pulmonary vasodilator responses to adenosine are partially dependent on the activation of adenosine 1 and 2 receptor pathways, and independent of the activation of cyclooxygenase activation, adenosine triphosphate-sensitive K + channels, or synthesis of nitric oxide in the pulmonary vascular bed of the cat. Conclusions Vasodepressor effects of adenosine are species specific, and this species specificity will impact the development of future testing and treatments for pulmonary arterial hypertension. Clinical studies are warranted to see if adenosine moieties could play a therapeutic role in patients with pulmonary arterial hypertension and/or other pulmonary pathogeneses.