Lower Extremity Peripheral Nerve Blocks for Post-operative Pain Control in a Multi-trauma Patient With Brugada Syndrome: A Literature Review and Case Report.

We describe the case of a 28-year-old man with Brugada syndrome who received single-shot adductor canal and sciatic nerve blocks for the management of post-operative pain related to extensive orthopedic injuries. Low-dose ropivacaine with glucocorticoid additives was administered without any EKG changes, arrhythmias, or syncopal sensations. The patient experienced pain relief for over 24 h and was monitored on telemetry with defibrillator pads as a cardiac precaution. This case adds a valuable data point in the limited canon of information on the safety and efficacy of regional anesthesia in Brugada syndrome for the perioperative physician.

The Telluride YAP/TAZ and TEAD Workshop: A Small Meeting with a Big Impact.

Funding the research needed to advance our understanding of rare cancers is very challenging [...].

Lipid emulsion for xenobiotic overdose: PRO.

Infusion of lipid emulsion for drug overdose arose as a treatment for local anaesthetic systemic toxicity (LAST) initially based on laboratory results in animal models with the subsequent support of favourable case reports. Following successful translation to the clinic, practitioners also incorporated lipid emulsion as a treatment for non-local anaesthetic toxicities but without formal clinical trials. Recent clinical trials demonstrate a benefit of lipid emulsion in antipsychotic, pesticide, metoprolol and tramadol overdoses. Formal trials of lipid emulsion in LAST may never occur, but alternative analytic tools indicate strong support for its efficacy in this indication; for example, lipid emulsion has obviated the need for cardiopulmonary bypass in most cases of LAST. Herein, we describe the pre-clinical support for lipid emulsion, evaluate the most recent clinical studies of lipid emulsion for toxicity, identify a possible dose-based requirement for efficacy and discuss the limitations to uncontrolled studies in the field.

After a century, Epinephrine's role in cardiac arrest resuscitation remains controversial.

BACKGROUND: Epinephrine is recommended in contemporary educational efforts by the American Heart Association (AHA) as central to adult Advanced Cardiac Life Support (ACLS). However, the International Liaison Committee on Resuscitation (ILCOR) 2019 recommendations update describes large evidentiary gaps for epinephrine use in cardiopulmonary resuscitation, highlighting that clinical and experimental evidence do not support the current AHA recommendations. OBJECTIVE: This controversies article was written as a response to updated AHA and ILCOR adult ACLS recommendations in late 2019. This report summarizes and evaluates the evidence surrounding epinephrine for cardiac arrest with a focus on the historical perspective of epinephrine research. DISCUSSION: According to the 2019 AHA ACLS guidelines, epinephrine is an integral component of adult out-of-hospital cardiac arrest resuscitation. Epinephrine improves rates of return of spontaneous circulation and might provide benefit at different doses or in select resuscitation scenarios, such asystole as an initial rhythm at onset of resuscitation efforts. However, evidence indicates potential harms with routine use of standard dose epinephrine (1 mg/10 mL), with no improvement in neurologic or long-term outcomes. CONCLUSIONS: Despite years of use and inclusion in resuscitation guidelines, epinephrine is not associated with improved neurologic outcomes. The AHA Emergency Cardiovascular Care committee should revise ACLS guidelines reflecting evidence that standard-dose epinephrine offers little benefit to successful patient recovery including neurologic outcomes. Future resuscitation guidelines should reflect this important consideration.

American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version.

The American Society of Regional Anesthesia and Pain Medicine (ASRA) periodically updates its practice advisories and associated cognitive aids. The 2020 version of the ASRA Local Anesthetic Systemic Toxicity checklist was created in response to user feedback, simulation studies and advances in medical knowledge. This report presents the 2020 version and discusses the rationale for its update.

Diet Practices, Body Mass Index, and Oral Health-Related Quality of Life in Adults with Periodontitis- A Case-Control Study.

OBJECTIVES: To assess and compare dietpractices, body mass index (BMI), and oral health-related quality of life (OHRQoL) in adults with and without periodontitis. METHODS: Demographics, health-related behaviors, BMI, dental and periodontal parameters, diet practices, and Oral Health Impact Profile-14 (OHIP-14) were collected from 62periodontitis patients and 100 controls without periodontitis. RESULTS: Havingperiodontitis was positively associated with male sex (p=0.004), older age (p<0.001), smoking pack-years (p = 0.006), weight (p = 0.008), BMI (p = 0.003), number of meals per day (p<0.001) and had a negative associationwithdecayed teeth (p = 0.013), alcohol (p = 0.006), and sweets (p = 0.007) consumption.Periodontitis patients were more likely to avoid carbonated beverages (p = 0.028), hot (p = 0.003), and cold drinks (p = 0.013), cold (p = 0.028), hardtextured (p = 0.002), and fibrous foods (p = 0.02) thanthe controls, and exhibited higher global OHIP-14 (p<0.001) andmost domain scores. Age (p<0.001), BMI (p =0.045), number of meals per day (p = 0.024), and global OHIP-14 score (p<0.001) remained positivelyassociated with periodontitis in the multivariate analysis. CONCLUSIONS: Periodontitis patients exhibitedhigher BMI and altered dietpracticesand OHRQoL as compared to controls. Assessment of diet practices, BMI,and OHRQoLshould bepart of periodontal work-up. Dentists and dietitians shouldcollaborate to design strategies to addressthese challenges.

Norepinephrine Induces Lung Microvascular Endothelial Cell Death by NADPH Oxidase-Dependent Activation of Caspase-3.

Norepinephrine (NE) is the naturally occurring adrenergic agonist that is released in response to hypotension, and it is routinely administered in clinical settings to treat moderate to severe hypotension that may occur during general anesthesia and shock states. Although NE has incontestable beneficial effects on blood pressure maintenance during hypotensive conditions, deleterious effects of NE on endothelial cell function may occur. In particular, the role of reactive oxygen species (ROS) and NADPH oxidase (Nox) on the deleterious effects of NE on endothelial cell function have not been fully elucidated. Therefore, we investigated the effects of NE on ROS production in rat lung microvascular endothelial cells (RLMEC) and its contribution to cell death. RLMEC were treated with NE (5 ng/mL) for 24 hours and ROS production was assessed by CellROX and DCFDA fluorescence. Nox activity was assessed by NADPH-stimulated ROS production in isolated membranes and phosphorylation of p47phox; cell death was assessed by flow cytometry and DNA fragmentation. Caspase activation was assessed by fluorescent microscopy. Nox1, Nox2, and Nox4 mRNA expression was assessed by real-time PCR. NE increased ROS production, Nox activity, p47phox phosphorylation, Nox2 and Nox4 mRNA content, caspase-3 activation, and RLMEC death. Phentolamine, an α 1-adrenoreceptor antagonist, inhibited NE-induced ROS production and Nox activity and partly inhibited cell death while ß-blockade had no effect. Apocynin and PEGSOD inhibited NE-induced caspase-3 activation and cell death while direct inhibition of caspase-3 abrogated NE-induced cell death. PEG-CAT inhibited NE-induced cell death but not caspase-3 activation. Collectively, these results indicate that NE induces RLMEC death via activation of Nox by α-adrenergic signaling and caspase-3-dependent pathways. NE has deleterious effects on RLMECs that may be important to its long-term therapeutic use.

Local Anesthetic Toxicity in the Geriatric Population.

This article provides a concise overview of local anesthetic systemic toxicity, its history, mechanisms, risk factors, prevention, clinical presentation, and treatment, with a special emphasis on issues specific to the geriatric population. The authors used MEDLINE, Scopus, and Google Scholar to search for original research articles (human and animal studies), registries data, case reports, review articles, and pertinent online publications using the combinations of the following search terms: local anesthetics, local anesthetic systemic toxicity, intralipid, lipid emulsion, Exparel, ultrasound-guidance, regional anesthesia, lidocaine, bupivacaine, ropivacaine, cocaine, procaine, tetracaine, levobupivacaine, liposomal bupivacaine, lignocaine. Local anesthetic systemic toxicity continues to occur despite the use of putatively less cardiotoxic formulations of local anesthetics and more common use of ultrasound guidance. The elderly appear to be at a disproportionately increased risk for toxicity owing to the presence of relevant comorbidities and decreased muscle mass. Examination of recent case reports involving patients over the age of 65 years demonstrates that inadvertent overdosing is responsible for some cases of local anesthetic systemic toxicity. Elderly patients are at increased risk of local anesthetic systemic toxicity. When considering use of local anesthetics in older patients, special attention should be paid to the presence of systemic disease and muscle wasting. The safety of regional anesthesia and multi-modal analgesia among these at-risk patients will be improved by educating physicians and staff to recognize and manage local anesthetic systemic toxicity.

Local Anesthetic Systemic Toxicity: A Narrative Literature Review and Clinical Update on Prevention, Diagnosis, and Management.

BACKGROUND: The objective of this narrative review of local anesthetic systemic toxicity is to provide an update on its prevention, diagnosis, and management. METHODS: The authors used a MEDLINE search of human studies, animal studies, and case reports and summarize findings following the American Society of Regional Anesthesia and Pain Medicine practice advisories on local anesthetic systemic toxicity. RESULTS: Between March of 2014 and November of 2016, there were 47 cases of systemic toxicity described. Twenty-two patients (47 percent) were treated with intravenous lipid emulsion and two patients (4.3 percent) died. Seizures were the most common presentation. The spectrum of presenting neurologic and cardiovascular symptoms and signs are broad and can be obscured by perioperative processes. Local anesthetic type, dosage, and volume; site of injection; and patient comorbidities influence the rate of absorption from the site of injection and biodegradation of local anesthetics. Consider discussing appropriate dosages as a component of the surgical "time-out." A large-volume depot of dilute local anesthetic can take hours before reaching peak plasma levels. Oxygenation, ventilation, and advanced cardiac life support are the first priorities in treatment. Lipid emulsion therapy should be given at the first sign of serious systemic toxicity with an initial bolus dose of 100 ml for adults weighing greater than 70 kg and 1.5 ml/kg for adults weighing less than 70 kg or for children. CONCLUSION: All physicians who administer local anesthetics should be educated regarding the nature of systemic toxicity and contemporary management algorithms that include lipid emulsion therapy.

The relative toxicity of brodifacoum enantiomers.

Brodifacoum (BDF) is a potent, long-acting anticoagulant rodenticide that can cause fatal poisoning in humans. The chemical structure of BDF includes 2 chiral carbons, resulting in 2 pairs of diastereomers, BDF-cis (R/S and S/R) and BDF-trans (R/R and S/S). However, the relative potency of these molecules is not known. The purpose of this study was to compare the in vitro and in vivo toxic effects of the 2 BDF diastereomer pairs. In adult Sprague-Dawley rats BDF-cis was significantly more toxic than BDF-trans (LD50 values of 219 versus 316 µg/kg, respectively) while racemic BDF had intermediate potency (266 µg/kg). In adult New Zealand white rabbits, BDF-cis had a longer half-life than BDF-trans which could contribute to its observed increased toxicity. Lastly, BDF-cis (10 µM), but not BDF-trans, damaged cultured SH-SY5Y human neuroblastoma cells by attenuating mitochondrial reductive capacity. Taken together, these data suggest that different toxic manifestations of BDF poisoning in mammals could be attributed, in part, to differences in relative enantiomer concentrations present in racemic formulations of this commercially-available toxicant.