Off-label Rescue Agents for Vasoplegic Syndrome after Cardiopulmonary Bypass

oai:anesthesiaejournal.com:article/155Abstract Introduction: Cardiovascular disease is the number one cause of death in the United States today1. Cardiopulmonary bypass (CPB) is a common technique used in the surgical management of cardiovascular disease. A relatively common complication of CPB is vasoplegia, which has an approximate incidence of anywhere from 5-25%1-8. Methylene blue is used to treat vasoplegic syndrome (VS) when higher dose vasopressors are ineffective. Vasoplegic syndrome (VS) is defined as a syndrome of low systemic vascular resistance (SVR) in the presence of normal or high cardiac output1-4. Generally, VS is characterized as a high cardiac output state (CI < 2.2 L/min/m2) with difficulty maintaining a mean arterial pressure (MAP) greater than 60 mmHg despite increasing vasopressor requirements1-3,7. The focus of this case report is to examine methylene blue’s effectiveness in treating vasoplegia after weaning from CPB. This case report will also compare and contrast methylene blue and another rescue agent, hydroxocobalamin, and how they combat vasoplegia. Case presentation: The case involved a 65-year-old male presenting for an aortic root and aortic valve replacement and removal of an abscess in his heart. The patient was under general anesthesia, put on cardiopulmonary bypass and then underwent a deep hypothermic circulatory arrest for the placement of the aortic root graft and aortic valve. Weaning from bypass was difficult as a result of vasoplegia, for which methylene blue was given when vasopressor requirements were increasing.   Discussion: Methylene blue is a guanylyl cyclase inhibitor that has been found to increase SVR and decrease vasopressor requirements in vasoplegic syndrome by inhibiting nitric oxide synthase (NOS), thus limiting the production of nitric oxide (NO) as well as inhibiting the enzyme guanylyl cyclase and preventing vasodilation5. The timing of administration of methylene blue is debatable, being that it is commonly given postoperatively, but the literature favors earlier administration in high-risk patients that will be placed on CPB2-5. Typical dosing for methylene blue is 2 mg/kg intravenously (IV) but increasing the dose to 3 mg/kg can be used to account for the larger volume of distribution (Vd) that is present in patients on CPB2. The only true contraindications for methylene blue are a hypersensitivity to the drug and a deficiency in the glucose-6-phosphate dehydrogenase, which is the enzyme that is responsible for turning methylene blue into its metabolites1-8. Treating VS with methylene blue after CPB has shown significantly quicker recovery and normal hemodynamics, shorter duration of vasopressor infusions, less incidence of renal complications, shorter length of stay (LOS) and less 30-day mortality6.  References: 1.Barnes TJ, Hockstein MA, Jabaley CS. Vasoplegia after cardiopulmonary bypass: A narrative review of pathophysiology and emerging targeted therapies. SAGE Open Med. 2020;8:2050312120935466. Published 2020 Jun 25. doi:10.1177/2050312120935466. Accessed January 25, 2021. 2.Ortoleva J, Shapeton A, Vanneman M, Dalia AA. Vasoplegia During Cardiopulmonary Bypass: Current Literature and Rescue Therapy Options. J Cardiothorac Vasc Anesth. 2020;34(10):2766-2775. doi:10.1053/j.jvca.2019.12.013. Accessed January 25, 2021. 3.Arevalo VN, Bullerwell ML. Methylene Blue as an Adjunct to Treat Vasoplegia in Patients Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass: A Literature Review. AANA J. 2018;86(6):455-463. Accessed January 25, 2021. 4.Busse LW, Barker N, Petersen C. Vasoplegic syndrome following cardiothoracic surgery-review of pathophysiology and update of treatment options. Crit Care. 2020;24(1):36. Published 2020 Feb 4. doi:10.1186/s13054-020-2743-8. Accessed January 25, 2021. 5.McCartney SL, Duce L, Ghadimi K. Intraoperative vasoplegia: methylene blue to the rescue!. Curr Opin Anaesthesiol. 2018;31(1):43-49. doi:10.1097/ACO.0000000000000548. Accessed January 25, 2021. 6.Habib AM, Elsherbeny AG, Almehizia RA. Methylene Blue for Vasoplegic Syndrome Postcardiac Surgery. Indian J Crit Care Med. 2018;22(3):168-173. doi:10.4103/ijccm.IJCCM_494_17. Accessed January 25, 2021. 7.Ortoleva JP, Cobey FC. A Systematic Approach to the Treatment of Vasoplegia Based on Recent Advances in Pharmacotherapy. J Cardiothorac Vasc Anesth. 2019;33(5):1310-1314. doi:10.1053/j.jvca.2018.11.025. Accessed January 25, 2021. 8.Furnish C, Mueller SW, Kiser TH, Dufficy L, Sullivan B, Beyer JT. Hydroxocobalamin Versus Methylene Blue for Vasoplegic Syndrome in Cardiothoracic Surgery: A Retrospective Cohort. J Cardiothorac Vasc Anesth. 2020;34(7):1763-1770. doi:10.1053/j.jvca.2020.01.033. Accessed January 25, 2021. 9.Cai Y, Mack A, Ladlie BL, Martin AK. The use of intravenous hydroxocobalamin as a rescue in methylene blue-resistant vasoplegic syndrome in cardiac surgery. Ann Card Anaesth. 2017;20(4):462-464. doi:10.4103/aca.ACA_88_17. Accessed January 25, 2021. 10.Kenny J-ES. Methylene Blue: The Drug You’ve Never Used PulmCCM. 2016. Accessed July 16, 2021