Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review.

PURPOSE OF REVIEW: Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens. RECENT FINDINGS: However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.

A comprehensive review of intraarticular knee injection therapy, geniculate injections, and peripheral nerve stimulation for knee pain in clinical practice.

The knee is the most common joint in adults associated with morbidity. Many pathologies are associated with knee damage, such as gout or rheumathoid arthritis, but the primary condition is osteoarthritis (OA). Not only can osteoarthritis cause significant pain, but it also can result in signficant disability as well. Treatment for this condition varies, starting off with oral analgesics and physical therapy to surgical total knee replacmenet. In the gamut of this various treatments, a conservative approach has included intra articular steroid injections. With time, researchers and clinicians determined that other components injected to the knee may additionally provide relief of this condition. In this investigation, we describe different types of knee injections such as platelet-rich plasma (PRP), hyaluronic acid, stem cells, and prolotherapy. Additionally, we describe the role of geniculate knee injections, radiofrequency, and periopheral nerve stimulation. These treatments should be considered for patients with knee pain refractory to conservative therapies.

Brexpiprazole for the Treatment of Schizophrenia and Major Depressive Disorder: A Comprehensive Review of Pharmacological Considerations in Clinical Practice.

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient's emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics.

Comparing incidence of emergence delirium between sevoflurane and desflurane in children following routine otolaryngology procedures.

BACKGROUND: Emergence delirium (ED) is a state of aggressive agitation that can occur temporarily in the process of emerging from anesthesia in children exposed to volatile or intravenous anesthetics. Emergence delirium is typically assessed using the published and validated Pediatric Emergence Delirium (PAED) Scale. Due to some variation in properties between sevoflurane and desflurane for maintenance of anesthesia after standard sevoflurane induction, we designed a prospective study to examine potential differences in emergence behavior and incidence of ED in children undergoing elective ear-nose-throat surgery. METHODS: Forty-six children aged 12 months-7 years were randomly assigned to receive either sevoflurane (N.=23) or desflurane (N.=23) for maintenance of general anesthesia. All patients were extubated awake in the OR, and upon arrival in the PACU, PAED scores were assessed every 15 minutes until discharged. In addition to PAED scores, time to tracheal extubation, emergence behavior, pain scores, and recovery complications were recorded. RESULTS: We found no significant difference in incidence of ED or peak PAED scores between sevoflurane and desflurane groups (12 [0-18] versus 12 [0-20]; P=0.79). There were no significant differences between desflurane and sevoflurane with respect to incidence of adverse events, such as nausea, vomiting, laryngospasm, or excessive secretions. CONCLUSIONS: In conclusion, the use of desflurane for maintenance of anesthesia did not significantly affect the incidence or duration of ED when compared to sevoflurane. However, desflurane did not demonstrate any increase in adverse events, which may support its routine use in this patient population.

Recovery following desflurane versus sevoflurane anesthesia for outpatient urologic surgery in elderly females.

BACKGROUND: An unresolved question is the time required for the ability to return to complex tasks following anesthesia. OBJECTIVES: This study aims to characterize the severity and duration of cognitive impairment following sevoflurane or desfluane anesthesia after brief surgery using tests of cognitive ability to objectively testing performance. PATIENTS AND METHODS: This study is a double blinded randomized controlled trial. Patients were randomized to receive either a desflurane or sevoflurane-based anesthetic. On the morning of the surgery the subjects performed baseline cognitive task tests (Mini Mental Status exam, Trail Making Test Part A and B, Digit Symbol Coding, Hopkins Verbal Learning Test, Stroop Color and Word Test to determine baseline cognitive function. Cognitive testing was repeated 30 minutes and 1 hour after surgery whereas Modified Telephone Interview for Cognitive Status (TICS-M) and Memory Aging Telephone Screen (MATS) was used on the following day of surgery. RESULTS: Trail Making Test Part B cognitive test showed statistically significant in comparison for pre and post exposure of anesthetics. This difference was seen in the desflurane group. Other cognitive tests did not show differences on exposure to the anesthetic gases. CONCLUSIONS: This study questioned the difference between volatile anesthetic agent's effects on patients completing a battery of neurocognitive tests attempting to answer if one agent has a more profound effect. Our study shows no statistically significant cognitive decline except for those in the Trail Making Part B in the Desflurane group. This conclusion is limited by the inherent limitations of the study, but does reinforce that the systemic inflammatory response from the surgery contributes cognitive impairment.

Desflurane versus opioid anesthesia for cardiac shunt procedures in infants with cyantoic congential heart disease.

BACKGROUND: Placement of a Blalock-Taussig (BT) shunt is frequently performed for palliation of cyanotic congenital heart disease (CCHD). OBJECTIVES: Inhalational anesthetics, when used in adult heart surgery, offer advantages of myocardial protection and decrease in use of inotropes, duration of ventilation, ICU and hospital length of stay (LOS).There is little literature, however, in the comparative use of inhalational and narcotic anesthesia in CCHD. PATIENTS AND METHODS: Following Institutional Ethical Review Board approval and parental consent, 35 patients presenting for BT shunt were prospectively randomized to receive either a desflurane anesthetic or a narcotic anesthetic. Institutional practice for all patients undergoing BT shunt is to undergo cardiopulmonary bypass (CPB) following median sternotomy. Induction was accomplished with 5-7% sevoflurane in 100% oxygen, 2ug/kg fentanyl, 0.05mg/kg midazolam and 0.1mg/kg vecuronium. After intubation, patients in the narcotic group (n=16) received an additional 5-10ug/kg fentanyl, 0.1mg/kg midazolam, 100% oxygen and vecuronium. Patients in the inhalational group (n=19) received desflurane, 0.6-1 MAC, 100% oxygen, 0.05mg/kg midazolam, IV paracetamol 15mg/kg and vecuronium. At the end of surgery, patients were transferred to the ICU and received IV paracetamol and midazolam. Ventilation was weaned when the patient was hemodynamically stable. Demographics, baseline, intra and post-op heart rates, duration of inotrope use, ICU and hospital LOS, pre and post-op creatinine and serious adverse events (SAE) were recorded. Data were analyzed using Student, paired t, Mann-Whitney U and Chi square/Fisher exact tests, P < 0.05 significant. RESULTS: Demographic data were similar, except for a modestly higher pre-op heart rate in the group receiving opioid anesthesia. Patients receiving desflurane had a significantly shorter duration of mechanical ventilation and length of ICU and hospital stay. Inotrope use was similar in both groups. The group receiving opioid anesthesia had an increase in creatinine post operatively which was not observed in the desflurane group. There was no difference in incidence of significant adverse events in either group. CONCLUSIONS: Use of inhalational anesthesia has increased in adult cardiac surgery and has proved to reduce duration of elective ventilation, decrease ICU and hospital LOS, and mortality. Inhalational anesthetics are less well-studied in CCHD. In the current study, desflurane was chosen because of its low solubility, decreased recovery time and lack of metabolism or organ system toxicities. Although it is a popular belief that desflurane is associated with tachycardia and airway irritation, findings of the current study are consistent with those of the previous works demonstrating a lack of these side effects below 1 MAC3. No hemodynamic instability was encountered and there was no evidence that desflurane exerted a negative inotropic effect. Markers of cardio protection were not examined, although desflurane may have had a renal protective effect compared to narcotic technique. In the current study, a desflurane anesthetic for BT shunt decreased the duration of mechanical ventilation and ICU and hospital LOS by nearly three days, with no difference in perioperative morbidity or mortality. Larger studies are required to determine whether these changes result in overall decreased complication rate and morbidity/mortality and whether desflurane has a cardio or renal protective effect in the patient population.

Efficacy of hyperbaric oxygen in patients with Crohn's disease: two case reports.

Crohn's disease is an inflammatory disease of the gastrointestinal tract, usually involving the ileum, that can lead to debilitating symptoms of abdominal pain, diarrhea and malabsorption during acute exacerbations. Because there is no known cause of the illness, treatment is based upon symptomatology and may ultimately require bowel resection if response to medical therapy is inadequate. Treatment with hyperbaric oxygen has shown promise in the reduction of inflammation associated with acute exacerbations of Crohn's disease, with alleviation of symptoms and an improvement in quality of life. We present two cases of pediatric patients with exacerbations of Crohn's disease who underwent cycles of hyperbaric oxygen therapy. Each patient was symptomatic and had no improvement despite prolonged medical therapy. Following treatment with hyperbaric oxygen, both patients showed resolution of the inflammatory lesions and improvement in conditions, allowing them to reduce drug therapy. Although the mechanisms by which hyperbaric oxygen reduce inflammation in Crohn's disease is poorly defined, this therapy seems to have offer a safe adjunct in the treatment of refractory exacerbations.

Hemodynamic response to repeated noxious cold pressor tests measured by functional near infrared spectroscopy on forehead.

The objective of this research was to assess the utility of a simple near infrared spectroscopy (NIRS) technology for objective assessment of the hemodynamic response to acute pain. For this exploration, we used functional near infrared spectroscopy (fNIRS) to measure the hemodynamic response on the forehead during three trials of a cold pressor test (CPT) in 20 adults. To measure hemodynamic changes at the superficial tissues as well as the intracranial tissues, two configurations of 'far' and 'near' source-detector separations were used. We identified two features that were found to be fairly consistent across all subjects. The first feature was the change of total hemoglobin (THb) concentration in a given condition divided by the duration of that condition [Formula: see text]. Statistical analyses revealed that during the first CPT trial [Formula: see text] significantly changed from its baseline value in all channels. Also, adaptation to repeated CPTs was observed in both [Formula: see text] parameter and the reported post-stimulus pain rating scores. The second feature was the difference between the maximum and the minimum of the evoked changes in the THb concentration (ΔTHb). A significant correlation was observed between the post-stimulus pain rating score and ΔTHb at all channels. An asymmetrical activity was observed only at the 'far' channels. These results suggest that fNIRS can potentially be used as a reliable technique for the assessment of the hemodynamic response to tonic pain induced by the CPT.

Therapeutic effect of hyperbaric oxygen on inclusion body myositis.

An inflammatory myopathy, inclusion body myositis (IBM) presents with progressive muscle weakness against a background of elevated creatine kinase and diffuse endomysial damage. Typically occurring in patients greater than 50 years of age, it is commonly misdiagnosed as polymyositis or other rheumatological disease and is often ineffectively treated with steroids [1]. The approach to IBM is frequently a clinical challenge due to its unique and often aberrant response to common treatment modalities. Here we report an apparent improvement in the clinical course of and associated laboratory findings in a patient with co-existing IBM following the use of hyperbaric oxygen therapy as an adjunct for managing ischemic colitis.