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High-Dose Intravenous Hydroxocobalamin for Persistent Vasoplegic Syndrome After Cardiac Surgery Mohamed Ben-Omran, MD1*, Ellen Huang, Pharmd2, Vijay S

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High-Dose Intravenous Hydroxocobalamin for Persistent Vasoplegic Syndrome After Cardiac Surgery Mohamed Ben-Omran, MD1*, Ellen Huang, Pharmd2, Vijay S ISSN: 2378-3656 Ben-Omran et al. Clin Med Rev Case Rep 2021, 8:335 DOI: 10.23937/2378-3656/1410335 Volume 8 | Issue 1 Clinical Medical Reviews Open Access and Case Reports CASE REPORT High-Dose Intravenous Hydroxocobalamin for Persistent Vasoplegic Syndrome after Cardiac Surgery Mohamed Ben-Omran, MD1*, Ellen Huang, PharmD2, Vijay S. Patel, MD3, Nadine Odo, BA, CCRC4, Taylor Glenn MD5 and Vaibhav Bora, MD6 1Assistant Professor, Anesthesiology and Perioperative Medicine, Augusta University, USA 2Pharmacist, Department of Pharmacy, Augusta University, USA 3 Associate Professor, Cardiothoracic Surgery, Augusta University, USA Check for updates 4Research Associate, Anesthesiology and Perioperative Medicine, Augusta University, USA 5Anesthesiology Resident, Intermountain Healthcare, Murray, Utah, USA 6Assistant Professor, Cleveland Medical Center, Case Western Reserve University, USA *Corresponding author: Mohamed Ben-Omran, MD, Assistant Professor of Anesthesiology and Critical Care Medicine, Department of Anesthesiology and Perioperative Medicine, Augusta University, 1120 15th St. BI-2144, Augusta, GA, 30912, USA, Tel: 6179538493; 7067210091, Fax: 706-721-7763 Abstract Glossary of Terms Vasoplegic syndrome is a vasodilatory shock characterized ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: by significant hypotension, normal or high cardiac output, Angiotensin II Receptor Blocker; CI: Cardiac Index; ICU: and increased requirement for intravenous fluid resusci- Intensive Care Unit; IL: Interleukin; LAD: Left Anterior De- tation and vasopressors. It is a relatively common compli- scending Coronary Artery; MAP: Mean Arterial Pressure; cation following cardiac surgery. We describe the case of NO: Nitric Oxide; SVG: Saphenous Vein Graft; SVR: Sys- a 77-year-old man who developed prolonged vasoplegic temic Vascular Resistance syndrome which was refractory to high doses of conven- tional vasopressors following coronary artery bypass graft surgery. Given the possible increased risk of serotonin Introduction syndrome associated with concurrent administration of Vasoplegia is a well-recognized complication fol- methylene blue and tramadol, we elected not to adminis- ter methylene blue in favor of hydroxocobalamin due to its lowing cardiac surgery. It is a relatively common syn- favorable adverse effect profile. A high dose of intravenous drome, with an incidence of 5-45%. The lowest and hydroxocobalamin was administered as a rescue agent in highest incidence are related to off-pump procedures the treatment of vasoplegic syndrome. The patient’s mean and patients with orthotopic heart transplantation, arterial blood pressure (MAP) increased. The vasopressors dosages were markedly reduced within the first hour and respectively [1,2]. As a vasodilatory shock, it is charac- subsequently discontinued within 18 hours. Hydroxocobal- terized by significant hypotension with a mean arterial amin was advocated for this patient as a safer alternative to pressure (MAP) < 50 mmHg, reduced systemic vascu- methylene blue in the setting of concomitant serotonergic lar resistance (SVR < 800 dynes-s/cm5), in a normal or drug use to avoid serotonin syndrome. high cardiac output setting (cardiac index [CI] > 2.2 L/ Keywords min/m2), normal or decreased filling pressures, and in- Hydroxocobalamin, Vitamin B12, Vasoplegia, Vesoplegic creased requirement for intravenous fluid resuscitation syndrome, Cardiac surgery, Serotonin toxicity, Serotonin and vasopressors [3]. It is associated with increased in- syndrome, Methylene blue tensive care unit (ICU) and hospital stays and increased morbidity and mortality secondary to multiorgan dys- Citation: Ben-Omran M, Huang E, Patel VS, Odo N, Glenn T, et al. (2021) High-Dose Intravenous Hy- droxocobalamin for Persistent Vasoplegic Syndrome after Cardiac Surgery. Clin Med Rev Case Rep 8:335. doi.org/10.23937/2378-3656/1410335 Accepted: January 28, 2021: Published: January 30, 2021 Copyright: © 2021 Ben-Omran M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduc- tion in any medium, provided the original author and source are credited. Ben-Omran et al. Clin Med Rev Case Rep 2021, 8:335 • Page 1 of 4 • DOI: 10.23937/2378-3656/1410335 ISSN: 2378-3656 function. Persistent refractory vasoplegia of > 36 hours Persistent vasoplegia remained at the top of the dif- has a mortality rate as high as 25% [4]. ferential diagnosis as the patient’s clinical course pro- gressed. Other possible causes of shock including pul- Here, we report the successful administration of a monary embolism and infection were evaluated. Trans- high dose of intravenous hydroxocobalamin as a rescue thoracic echocardiology was negative for pericardial agent to manage persistent refractory vasoplegic syn- effusion and regional wall motion abnormalities. Right drome following cardiopulmonary bypass surgery. Writ- ventricular function was normal without strain or dilata- ten HIPAA authorization and written informed consent tion, and no gross valvular or ascending aortic patholo- were obtained from the patient who agreed to have his gies were noted. No clinical or laboratory findings were anonymized clinical information published in this arti- suggestive of sepsis. cle. The patient’s chronic back pain had been controlled Case Description with tramadol, which was resumed postoperatively. A 77-year-old man presented to the emergency de- Given the possible increased risk of serotonin syndrome partment with a complaint of an episode of dizziness associated with concurrent administration of methy- and lightheadedness. His medical history was significant lene blue and tramadol, we favored administration of for coronary artery disease, hypertension, hyperlipid- hydroxocobalamin over methylene blue for refractory emia, and chronic back pain. His medications included vasoplegia. Five grams of intravenous hydroxocobala- atenolol, amlodipine, simvastatin, and tramadol. A 12- min (Cyanokit, Meridian Medical Technologies, Colum- lead electrocardiogram revealed bigeminy. The patient bia, MD) was administered over 15 minutes as a rescue was admitted for a cardiac workup. Results of the cardi- treatment for refractory vasoplegia. Arterial blood pres- ac stress test suggested ischemic changes. The left heart sure increased to a level sufficient for reducing norepi- catheterization revealed multivessel coronary artery dis- nephrine dosage to half in the first hour, tapering it off ease (MVCAD) with 95% occlusion of the distal left main within 4 hours, and discontinuing vasopressin within 18 and left anterior descending (LAD), coronary artery, 70% hours. This improvement in hemodynamic status and occlusion of the obtuse marginal (OM), and 80% occlu- sustained increase in the MAP enabled the patient to sion of distal right coronary artery (RCA). The left ven- tolerate diuresis, achieving the targeted negative flu- tricular ejection fraction (LVEF) was preserved (60%). id balance and permitting the addition of metoprolol the following day. The patient was transferred to the The patient thrice underwent coronary artery bypass wardon postoperative day 4, and to a rehabilitation grafting: Left internal mammary artery to LAD, saphe- center after 7 days of hospitalization. nous vein graft (SVG) to the distal posterior descending artery, and SVG to obtuse marginal artery. Total cardio- Discussion pulmonary pump time was 75 minutes. There were no The precise mechanisms that cause vasoplegic syn- intra-operative complications. The patient was sedat- drome are complex and not fully understood; however, ed and intubated while being transported to the ICU, it has been attributed to increased production of sev- where he was extubated within a few hours of admis- eral vasodilating mediators such as interleukins (ILs), sion. The patient remained A-paced at 90 bpm and re- mainly IL1, IL6, IL8, tumor necrosis factor, and a rela- quired a small dose of norepinephrine (0.02-0.03 mcg/ tive or absolute deficiency of vasopressin, in addition kg/min) to maintain a goal MAP of > 65 mmHg; CI re- to nitric oxide (NO) dysregulation [2,5,6]. Long cardio- mained above 2 L/m2. pulmonary bypass time; blood transfusion; sepsis; use On postoperative day 1, the patient continued to of a ventricular assist device; low ejection fraction (< require higher dosages (0.05-0.08 mcg/kg/min) of nor- 35%); and recent use of angiotensin-converting enzyme epinephrine infusion. Pulmonary artery catheter pa- inhibitors (ACEI), angiotensin II receptor blockers (ARB), rameters indicated vasoplegia, which was unresponsive beta-blockers, or calcium channel blockers, have been to multiple fluid boluses challenges. That was further identified as risk factors for the development of vaso- complicated by a short episode of atrial fibrillation with plegic syndrome after cardiac surgery [7-9]. In our pa- a rapid ventricular response that converted back to si- tient, the cardiopulmonary bypass time was 75 minutes, nus rhythm after a 150 mg bolus dose of intravenous the patient received 1L of autologous and 290 mL of cell amiodarone. Despite this conversion, the patient’s he- saver blood, and had not received ACEI or ARBs in the modynamic status continued to worsen, urine output 24 hours prior to surgery. decreased, and norepinephrine requirement increased Alpha-1 adrenoreceptor agonists and vasopressin to 0.25 mcg/kg/min, which necessitated the addition continue to be the main and the first-line treatment in of vasopressin
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