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Hydroxocobalamin in Vasoplegic Syndrome: Effects of Poor-Adherence to Pharmaceutical Guidelines and Criteria for Use of B-12 Fritz Gerald Charles1,2, M.D., Kenneth Leonard4, PharmD, Leslie Murray3, Ph.D., Chris Giordano1,2, M.D., Bruce Spiess1,2,5 M.D 1College of Medicine, 2Department of Anesthesiology, 3Department of Chemistry, 4Department of Pharmacy, 5Division of Cardiothoracic Anesthesiology, University of Florida College of Medicine, Gainesville FL 32610 Introduction Results Vasoplegic syndrome, a common condition seen after prolonged The Big Idea The total number of patients that properly received B-12 period on cardiopulmonary bypass (CPB) and liver according to proper pharmaceutical guideline was 3/12 (25 transplantation, is a serious state of severe hypotension that is percent) of the patients. Four (4/12) patients did not meet resistant to catecholamines. Due to the high mortality rate criteria for administration of B-12 as they had MAP > 55. One associated with vasoplegia, there have been growing interests in Many of the vasodilating gasotransmitters that are patient did not meet criteria as an infusion of vasopressin was finding effective therapeutic drugs to manage the hemodynamic believed to be responsible for the hemodynamic never started. An additional 4/12 cases did not meet criteria effects resulting from the widespread systemic vasodilation based on the maximum infusion guideline for involved (1). Methylene blue (MB), which is the current standard disturbance seen in vasoplegia have a higher affinity for Epinephrine/Norepinephrine which was never achieved prior to therapy used to treat catecholamine-resistant vasoplegia, has B-12 dosing. been falling out of favor with emerging evidence showing high the core cobalt of vitamin B-12 than they do for other morbidity, and increased mortality (2). Recently, there have been metalloproteins. We postulate that such a molecular The effects of B12 on MAP was very similar to our earlier growing numbers of case reports and a series reporting reports and those reported in the case series by Shah et al. successful use of Hydroxocobalamin (HyCob) in vasoplegia. affinity is why vitamin B-12 may be highly useful in cases There were 10/12 (83.33%) patients who experienced an Given the enthusiasm surrounding the use of Hycob for this increased in MAP by at least 1mmHg at 5 minutes or less. The purpose, it is no surprise that the clinical case series of 37 of vasoplegia. range of MAP achieved at 5min was 1-26mmHg. patients published by Shah et al. showed that about 30% of Nitric Oxide: cases involving the use of HyCob in vasoplegic syndrome did not Figure 1. Methylene blue vs. hydroxocobalamin meet criteria for administration. In this retrospective review, we hope to determine if we need to tighten or enhance guidelines for proper use of HyCob in vasoplegia, thereby decreasing the unnecessary exposure of our patients to HyCob and reducing waste of this costly drug. Methods We performed a retrospective chart review of 12 patients undergoing cardiac surgery using cardiopulmonary bypass NO signaling pathway. NO is Hycob is able to block all three main produced from L-arginine by NOS. Methylene blue affects this (CPB) and liver transplant between May 30th, 2018 to January steps of the NO signaling pathway. It NO induces sGC to increase cGMP, pathway at two different locations. Conclusion inhibits the production of NO by iNOS which leads to a decrease in It inhibits the production of NO by 21st, 2020. The age range was between 21 to 84-years old. and blocks the NO-induced activation of intracellular calcium, and thereby iNOS and blocks the NO-induced sGC, as well as scavenges free NO in Reasonable biochemical explanations exist for the probable causes smooth muscle cell relaxation activation of sGC. the blood. Criteria for use of B-12 is refractory vasoplegia defined as MAP (vasodilation). beneficial effects of B-12 in treating vasoplegia. However, future < 55 mmHg (and CI > 2.5) despite norepinephrine/epinephrine research is needed to elucidate if and how these biochemical Scan the QR Code for mechanisms are causally involved in effective clinical responders equal to or greater than 0.2 mcg/kg/min (or phenylephrine equal more information. to or above 2 mcg/kg/min) and vasopressin equal to or greater and non-responders. Proper guidelines and criteria should be than 0.03 units/min. Dosing use was 5g of CyanokitTM , with followed prior to administration of B-12 to avoid confounding option to re-dose an additional 5g, if patient responds to first errors that may result in under- or over-estimation of the effect of dose (Maximum dose is 10g). the drug..

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