Vasoplegic syndrome, a possible complication of cardiopulmonary bypass, is a critical state of unregulated systemic vasodilation with decreased vascular resistance and a pathological insensitivity to conventional inotropes and vasoconstrictors. This case demonstrates the use of methylene blue and hydroxocobalamin as medications in the treatment of refractory vasoplegic syndrome in the context of cardiac surgery due to their differences in mechanism of action. A 24-year-old female with history of intravenous drug abuse and hepatitis C infection underwent mitral valve repair for infective endocarditis. Preoperative transesophageal echocardiography showed normal right ventricular function, left ventricular ejection fraction of 65%–75%, and severe mitral regurgitation with vegetation. In order to maintain a mean arterial pressure over 60 mmHg during cardiopulmonary bypass, norepinephrine, epinephrine, and vasopressin infusions were required. Given the patient’s minimal response to these medications, a 1.5 mg/kg bolus of intravenous methylene blue was also given intraoperatively; vasoplegic syndrome remained refractory in the post-cardiopulmonary bypass period. A 5 g dose of intravenous hydroxocobalamin was administered in the intensive care unit postoperatively. Postoperative liver function tests were abnormal, and post-cardiopulmonary bypass transesophageal echocardiography revealed mildly decreased right ventricular function. While in the intensive care unit, the patient was placed on venoarterial extracorporeal membrane oxygenation and underwent therapeutic plasma exchange. Vasopressors were weaned over the course of the next 24 h. The patient was able to be transferred out of the intensive care unit on postoperative day 5. Traditional vasoconstrictors activate signal transduction pathways that lead to myosin phosphorylation. Vasodilatory molecules such as nitric oxide (NO) activate the enzyme soluble guanylyl cyclase (sGC), ultimately leading to the dephosphorylation of myosin. Nitric Oxide Synthase (NOS) can potentially increase NO levels 1000-fold when activated by inflammatory cytokines. Methylene blue is a direct inhibitor of NOS. It also binds and inhibits sGC. Hydroxocobalamin is a direct inhibitor of NO, likely inhibits NOS and may also act through additional mechanisms.

between the TGF-b1 treated cells (11.56%AE4.83%) and the TGF-b1+rhPRG4 treated cells (10.66%AE4.16%) (unpaired t-test, N¼5, p¼NS). Collagen fiber alignment was used as a measure of local extracellular matrix remodeling by single human cardiac myofibroblasts embedded in 3D collagen matrices using confocal microscopy (Figure). Collagen fiber alignment by human cardiac myofibroblasts in the presence of TGF-b1 (normalized ratio: 1.17AE0.03) was attenuated with the addition of rhPRG4 (0.90AE0.05) (unpaired t-test, N¼3, p < 0.05). Cell roundness was measured to determine effects of rhPRG4 on cell morphology. Cell roundness of human cardiac myofibroblasts in the presence of TGF-b1 (normalized ratio: 0.60AE0.09) was increased with the addition of rhPRG4 (0.84AE0.06) (unpaired ttest, N¼3, p < 0.05). CONCLUSION: We show for the first time that rhPRG4 attenuates human cardiac myofibroblast activity and cellmediated collagen matrix remodeling. These data support the possibility that restoring PRG4 content in the pericardial space may prevent intrathoracic adhesion development after cardiac surgery.

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Background: We sought to evaluate differences in primary anesthetic type used in arteriovenous access creation with the hypothesis that administration of regional anesthesia and monitored anesthesia care (MAC) with local anesthesia as the primary anesthetic has increased over time. Methods: National Anesthesia Clinical Outcomes Registry data were retrospectively evaluated. Covariates were selected a priori within multivariate models to determine predictors of anesthetic type in adults who underwent elective arteriovenous access creation between 2010 and 2018. Results: A total of 144,392 patients met criteria; 90,741 (62.8%) received general anesthesia. The use of regional anesthesia and MAC decreased over time (8.0%–6.8%, 36.8%–27.8%, respectively; both p < 0.0001). Patients who underwent regional anesthesia were more likely to have ASA physical status >III and to reside in rural areas (52.3% and 12.9%, respectively; both p < 0.0001). Patients who underwent MAC were more likely to be older, male, receive care outside the South, and reside in urban areas (median age 65, 56.8%, 68.1%, and 70.8%, respectively; all p < 0.0001). Multivariate analysis revealed that being male, having an ASA physical status >III, and each 5-year increase in age resulted in increased odds of receiving alternatives to general anesthesia (regional anesthesia adjusted odds ratios (AORs) 1.06, 1.12, and 1.26, MAC AORs 1.09, 1.2, and 1.1, respectively; all p < 0.0001). Treatment in the Midwest, South, or West was associated with decreased odds of receiving alternatives to general anesthesia compared to the Northeast (regional anesthesia AORs 0.28, 0.38, and 0.03, all p < 0.0001; MAC 0.76, 0.13, and 0.43, respectively; all p < 0.05). Conclusions: Use of regional anesthesia and MAC with local anesthesia for arteriovenous access creation has decreased over time with general anesthesia remaining the primary anesthetic type. Anesthetic choice, however, varies with patient characteristics and geography.