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

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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.

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.

Blood Density Is Nearly Equal to Water Density: A Validation Study of the Gravimetric Method of Measuring Intraoperative Blood Loss.

Purpose. The gravimetric method of weighing surgical sponges is used to quantify intraoperative blood loss. The dry mass minus the wet mass of the gauze equals the volume of blood lost. This method assumes that the density of blood is equivalent to water (1 gm/mL). This study's purpose was to validate the assumption that the density of blood is equivalent to water and to correlate density with hematocrit. Methods. 50 µL of whole blood was weighed from eighteen rats. A distilled water control was weighed for each blood sample. The averages of the blood and water were compared utilizing a Student's unpaired, one-tailed t-test. The masses of the blood samples and the hematocrits were compared using a linear regression. Results. The average mass of the eighteen blood samples was 0.0489 g and that of the distilled water controls was 0.0492 g. The t-test showed P = 0.2269 and R (2) = 0.03154. The hematocrit values ranged from 24% to 48%. The linear regression R (2) value was 0.1767. Conclusions. The R (2) value comparing the blood and distilled water masses suggests high correlation between the two populations. Linear regression showed the hematocrit was not proportional to the mass of the blood. The study confirmed that the measured density of blood is similar to water.

Epinephrine induces rapid deterioration in pulmonary oxygen exchange in intact, anesthetized rats: a flow and pulmonary capillary pressure-dependent phenomenon.

BACKGROUND: Previous studies indicate epinephrine adversely affects arterial oxygenation when administered in a rat model of local anesthetic overdose. The authors tested whether epinephrine alone exerts similar effects in the intact animal. METHODS: Anesthetized rats received a single intravenous injection of epinephrine (25, 50, or 100 mcg/kg); matched cohorts were pretreated with phentolamine (100 mcg/kg); n = 5 for each of the six treatment groups. Arterial pressure and blood gases were measured at baseline, 1 and 10 min after epinephrine administration. Pulmonary capillary pressures during epinephrine infusion with normal and increased flows were measured in an isolated lung preparation. RESULTS: Epinephrine injection in the intact animal caused hypoxemia, hypercapnia, and acidosis at all doses. Arterial oxygen tension was reduced within 1 min of injection. Hyperlactatemia occurred by 10 min after 50 and 100 mcg/kg. Rate pressure product was decreased by 10 min after 100 mcg/kg epinephrine. Pretreatment with phentolamine attenuated these effects except at 100 mcg/kg epinephrine. In the isolated lung preparation, epinephrine in combination with increased pulmonary flow increased pulmonary capillary pressure and lung water. CONCLUSIONS: Bolus injection of epinephrine in the intact, anesthetized rat impairs pulmonary oxygen exchange within 1 min of treatment. Effects were blunted by α-adrenergic receptor blockade. Edema occurred in the isolated lung above a threshold pulmonary capillary pressure when epinephrine treatment was coupled with an increase in pulmonary flow. These results potentially argue against using traditional doses of epinephrine for resuscitation, particularly in the anesthetized patient.

Nanomedicines for chronic non-infectious arthritis: the clinician's perspective.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues. Conceivably, biocompatible, biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could represent a promising therapeutic approach for RA and OA. To this end, the unique physicochemical properties of drug-loaded nanocarriers coupled with pathophysiological characteristics of inflamed joints amplify bioavailability and bioactivity of DMARNs and promote their selective targeting to inflamed joints. This, in turn, minimizes the amount of drug required to control articular inflammation and circumvents collateral damage to healthy tissues. Thus, nanomedicine could provide selective control both in space and time of the inflammatory process in affected joints. However, bringing safe and efficacious DMARNs for RA and OA to the marketplace is challenging because regulatory agencies have no official definition of nanotechnology, and rules and definitions for nanomedicines are still being developed. Although existing toxicology tests may be adequate for most DMARNs, as new toxicity risks and adverse health effects derived from novel nanomaterials with intended use in humans are identified, additional toxicology tests would be required. Hence, we propose that detailed pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA, including risks to the general population, must be conducted before clinical trials begin.

Nanomedicines for chronic non-infectious arthritis: the clinician's perspective.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues. Conceivably, biocompatible, biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could represent a promising therapeutic approach for RA and OA. To this end, the unique physicochemical properties of drug-loaded nanocarriers coupled with pathophysiological characteristics of inflamed joints amplify bioavailability and bioactivity of DMARNs and promote their selective targeting to inflamed joints. This, in turn, minimizes the amount of drug required to control articular inflammation and circumvents collateral damage to healthy tissues. Thus, nanomedicine could provide selective control both in space and time of the inflammatory process in affected joints. However, bringing safe and efficacious DMARNs for RA and OA to the marketplace is challenging because regulatory agencies have no official definition of nanotechnology, and rules and definitions for nanomedicines are still being developed. Although existing toxicology tests may be adequate for most DMARNs, as new toxicity risks and adverse health effects derived from novel nanomaterials with intended use in humans are identified, additional toxicology tests would be required. Hence, we propose that detailed pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA, including risks to the general population, must be conducted before clinical trials begin.

American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2012 version.

In 2010, the American Society of Regional Anesthesia and Pain Medicine (ASRA) issued a practice advisory on local anesthetic systemic toxicity (LAST). The executive summary of this work contained a document that was intended to serve as a checklist for the management of LAST. Based on testing the checklist during a simulated episode of LAST, ASRA has issued an updated version that should replace the previous 2010 version. Electronic copies of the ASRA Checklist, suitable for lamination and inclusion in a local anesthetic toxicity kit, are available from the ASRA Web site (www.asra.com).