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1
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Puchany AJ, Hilmi I. Post-reperfusion syndrome in liver transplant recipients: What is new in prevention and management? World J Crit Care Med 2025; 14:101777. [DOI: 10.5492/wjccm.v14.i2.101777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/22/2024] [Accepted: 12/19/2024] [Indexed: 02/27/2025] Open
Abstract
Post-reperfusion syndrome (PRS) in liver transplant recipients remains one of the most dreaded complications in liver transplant surgery. PRS can impact the short-term and long-term patient and graft outcomes. The definition of PRS has evolved over the years, from changes in arterial blood pressures and heart and/or decreases in the systemic vascular resistance and cardiac output to including the fibrinolysis and grading the severity of PRS. However, all that did not reflect on the management of PRS or its impact on the outcomes. In recent years, new scientific techniques and new technology have been in the pipeline to better understand, manage and maybe prevent PRS. These new methods and techniques are still in the infancy, and they have to be proven not in prevention and management of PRS but their effects in the patient and graft outcomes. In this article, we will review the long history of PRS, its definition, etiology, management and most importantly the new advances in science and technology to prevent and properly manage PRS.
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Affiliation(s)
- Austin James Puchany
- Department of Anesthesiology & Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
| | - Ibtesam Hilmi
- School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States
- Department of Anesthesiology and Perioperative Medicine, Clinical and Translational Science Institute, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, United States
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2
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Nguyen A, Bouajram R, Brzezinski M, Hassanipour S, Gordon D, Trinh B, Deuse T, Venado A, Hays S, Singer J, Kukreja J. Hydroxocobalamin for the treatment of vasoplegia after lung transplantation: A case series. JHLT OPEN 2025; 7:100189. [PMID: 40144827 PMCID: PMC11935413 DOI: 10.1016/j.jhlto.2024.100189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
Background The use of hydroxocobalamin following lung transplantation has not been previously reported. We present a series of 3 cases where hydroxocobalamin was used to treat postoperative vasoplegia. Methods We conducted a single-center, retrospective review of lung transplantation recipients from January 2016 to December 2020. We used cumulative vasopressor index to standardize vasopressor dose administered and mean arterial pressure at 2- and 24-hour time-points following hydroxocobalamin administration to assess treatment effectiveness. Results We identified 3 male patients aged 49 to 62, with lung allocation scores between 89.9 and 90.6, requiring extracorporeal membrane oxygenation support (pre- and post-transplant for 5, 5, 9 and 8, 2, 2 days, respectively). Each patient received hydroxocobalamin 5,000 mg infused over 15 minutes, with patient #3 receiving an additional 6 doses over the subsequent 4 days. At the 2-hour time-point, mean arterial pressure increased in all patients (+11%, +17%, and +13%, respectively), although cumulative vasopressor indexes were inconsistent. At 24 hours, patients #1 and #2 demonstrated a marked increase in mean arterial pressure (36% and 23%, respectively) and a decrease in cumulative vasopressor index, while patient #3 displayed stable with slight reduction in cumulative vasopressor index and mean arterial pressure values. No allergic reactions were observed. Patient #3 developed methemoglobinemia and a medication-related false increase in triglycerides. All 3 patients were discharged home. Conclusions Hydroxocobalamin may be a valuable adjunct in managing refractory vasoplegia following lung transplantation.
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Affiliation(s)
- Anh Nguyen
- Baylor College of Medicine, Houston, Texas
| | - Rima Bouajram
- University of California San Francisco, San Francisco, California
| | - Marek Brzezinski
- University of California San Francisco, San Francisco, California
| | | | - David Gordon
- University of California San Francisco, San Francisco, California
| | - Binh Trinh
- University of California San Francisco, San Francisco, California
| | - Tobias Deuse
- University of California San Francisco, San Francisco, California
| | - Aida Venado
- University of California San Francisco, San Francisco, California
| | - Steve Hays
- University of California San Francisco, San Francisco, California
| | - Jonathan Singer
- University of California San Francisco, San Francisco, California
| | - Jasleen Kukreja
- University of California San Francisco, San Francisco, California
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3
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Pai SL, Torp KD, Insignares VC, DeMaria S, Giordano CR, Logvinov II, Li Z, Chadha R, Aniskevich S. Use of hydroxocobalamin to treat intraoperative vasoplegic syndrome refractory to vasopressors and methylene blue during liver transplantation. Clin Transplant 2024; 38:e15271. [PMID: 38485687 DOI: 10.1111/ctr.15271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 01/16/2024] [Accepted: 02/11/2024] [Indexed: 03/19/2024]
Abstract
INTRODUCTION For patients with catecholamine-resistant vasoplegic syndrome (VS) during liver transplantation (LT), treatment with methylene blue (MB) and/or hydroxocobalamin (B12) has been an acceptable therapy. However, data on the effectiveness of B12 is limited to case reports and case series. METHODS We retrospectively reviewed records of patients undergoing LT from January 2016 through March 2022. We identified patients with VS treated with vasopressors and MB, and abstracted hemodynamic parameters, vasopressor requirements, and B12 administration from the records. The primary aim was to describe the treatment efficacy of B12 for VS refractory to vasopressors and MB, measured as no vasopressor requirement at the conclusion of the surgery. RESULTS One hundred one patients received intraoperative VS treatment. For the 35 (34.7%) patients with successful VS treatment, 14 received MB only and 21 received both MB and B12. Of the 21 patients with VS resolution after receiving both MB and B12, 17 (89.5%) showed immediate, but transient, hemodynamic improvements at the time of MB administration and later showed sustained response to B12. CONCLUSION Immediate but transient hemodynamic response to MB in VS patients during LT supports the diagnosis of VS and should prompt B12 administration for sustained treatment response.
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Affiliation(s)
- Sher-Lu Pai
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Klaus D Torp
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Vianca C Insignares
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Samuel DeMaria
- Department of Anesthesiology, Perioperative and Pain Medicine, The Mount Sinai Hospital, New York, New York, USA
| | - Chris R Giordano
- Department of Anesthesiology, University of Florida Health, Gainesville, Florida, USA
| | - Ilana I Logvinov
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Zhuo Li
- Department of Quantitative Health Science, Mayo Clinic, Jacksonville, Florida, USA
| | - Ryan Chadha
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | - Stephen Aniskevich
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida, USA
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4
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Gökdemir BN, Çekmen N. Vasoplegic Syndrome and Anaesthesia: A Narrative Review. Turk J Anaesthesiol Reanim 2023; 51:280-289. [PMID: 37587654 PMCID: PMC10440482 DOI: 10.4274/tjar.2023.221093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 02/23/2023] [Indexed: 08/18/2023] Open
Abstract
Vasoplegic syndrome (VS) is defined as low systemic vascular resistance, normal or high cardiac output, and resistant hypotension unresponsive to vasopressor agents and intravenous volume. VS is a frequently encountered complication in cardiovascular and transplantation surgery, burns, trauma, pancreatitis, and sepsis. The basis of the pathophysiology is associated with an imbalance of vasodilator and vasoconstrictive structure in vascular smooth muscle cells and is highly complex. The pathogenesis of VS has several mechanisms, including overproduction of iNO, stimulation of ATP-dependent K+ channels and NF-κB, and vasopressin receptor 1A (V1A-receptor) down-regulation. Available treatments involve volume and inotropes administration, vasopressin, methylene blue, hydroxocobalamin, Ca++, vitamin C, and thiamine, and should also restore vascular tone and improve vasoplegia. Other treatments could include angiotensin II, corticosteroids, NF-κB inhibitor, ATP-dependent K+ channel blocker, indigo carmine, and hyperbaric oxygen therapy. Despite modern advances in treatment, the mortality rate is still 30-50%. It is challenging for an anaesthesiologist to consider this syndrome's diagnosis and manage its treatment. Our review aims to review the diagnosis, predisposing factors, pathophysiology, treatment, and anaesthesia approach of VS during anaesthesia and to suggest a treatment algorithm.
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Affiliation(s)
- Begüm Nemika Gökdemir
- Department of Anaesthesiology and Reanimation, Başkent University Faculty of Medicine, Ankara, Turkey
| | - Nedim Çekmen
- Department of Anaesthesiology and Reanimation, Başkent University Faculty of Medicine, Ankara, Turkey
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5
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Brokmeier HM, Seelhammer TG, Nei SD, Gerberi DJ, Mara KC, Wittwer ED, Wieruszewski PM. Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue. J Cardiothorac Vasc Anesth 2023:S1053-0770(23)00241-0. [PMID: 37147207 DOI: 10.1053/j.jvca.2023.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/30/2023] [Accepted: 04/03/2023] [Indexed: 05/07/2023]
Abstract
Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.
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Affiliation(s)
| | | | - Scott D Nei
- Department of Pharmacy, Mayo Clinic, Rochester, MN
| | | | - Kristin C Mara
- Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN
| | | | - Patrick M Wieruszewski
- Department of Pharmacy, Mayo Clinic, Rochester, MN; Department of Anesthesiology, Mayo Clinic, Rochester, MN.
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6
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Blaha M, Blais M, Olson L. The Durability of Intravenous Hydroxocobalamin in Vasoplegia. Cureus 2023; 15:e38307. [PMID: 37255913 PMCID: PMC10226765 DOI: 10.7759/cureus.38307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2023] [Indexed: 06/01/2023] Open
Abstract
Objectives Refractory distributive shock (vasoplegia) has been treated with intravenous (IV) hydroxocobalamin (B12), but its use is poorly characterized. The objective of this study was to quantify the duration of hemodynamic improvement after B12 administration. Materials and methods This was a retrospective chart review of adult patients who received IV B12 while on vasopressors in the intensive care unit. Patients were divided into two groups: responders (≥10% decrease in baseline vasopressor requirements within 60 minutes of B12 administration) and non-responders. Results A total of 16 patients were included, and five (31%) met the 'responder' criteria. The median time to respond was 15 minutes, and the response was maintained for a median of 210 minutes. The baseline median norepinephrine equivalent (NEE) rate was 32.9 mcg/min in responders and 24.7 mcg/min in non-responders. Responders' NEE requirements decreased to 16.7 mcg/min after 15 minutes and 14.8 mcg/min after 60 minutes. All responders and 10 (91%) non-responders were mechanically ventilated; both groups were mostly male (60% and 91%) and had a median age of 54 years and 58 years, respectively. A total of 4 (80%) responders and 10 (91%) non-responders died while hospitalized. IV B12 was administered as 5 g over 15 minutes in all but two patients (one responder and one non-responder), who each received 5 g of B12 over 360 minutes. Conclusion Vasopressor requirements decreased rapidly in 31% of patients after B12 administration and remained so for a median of 210 minutes.
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Affiliation(s)
| | - Meghan Blais
- Department of Pharmacy, Nebraska Medicine, Omaha, USA
| | - Logan Olson
- Department of Pharmacy, Nebraska Medicine, Omaha, USA
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7
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Brennan KA, Bhutiani M, Kingeter MA, McEvoy MD. Updates in the Management of Perioperative Vasoplegic Syndrome. Adv Anesth 2022; 40:71-92. [PMID: 36333053 DOI: 10.1016/j.aan.2022.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Vasoplegic syndrome occurs relatively frequently in cardiac surgery, liver transplant, major noncardiac surgery, in post-return of spontaneous circulation situations, and in pateints with sepsis. It is paramount for the anesthesiologist to understand both the pathophysiology of vasoplegia and the different treatment strategies available for rescuing a patient from life-threatening hypotension.
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Affiliation(s)
- Kaitlyn A Brennan
- Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Avenue South, MAB 422, Nashville, TN 37212, USA
| | - Monica Bhutiani
- Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Avenue South, VUH 4107, Nashville, TN 37212, USA
| | - Meredith A Kingeter
- Anesthesia Residency, Vanderbilt University Medical Center, 1215 21st Avenue South, Suite 5160 MCE NT, Nashville, TN 37212, USA
| | - Matthew D McEvoy
- VUMC Enhanced Recovery Programs, Department of Anesthesiology, Vanderbilt University Medical Center, 1301 Medical Center Drive, TVC 4648, Nashville, TN 37232, USA.
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8
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Boettcher BT, Woehlck HJ, Makker H, Pagel PS, Freed JK. Hydroxocobalamin for treatment of catecholamine-resistant vasoplegia during liver transplantation: A single-center series of 20 cases. Int J Surg Case Rep 2022; 98:107488. [PMID: 35981485 PMCID: PMC9399471 DOI: 10.1016/j.ijscr.2022.107488] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 08/03/2022] [Accepted: 08/07/2022] [Indexed: 11/25/2022] Open
Abstract
Introduction Catecholamine-resistant vasoplegia is a potentially devastating complication during liver transplantation. Hydroxocobalamin has emerged as a treatment for vasoplegia associated with cardiac surgery, liver transplantation, and septic shock. Presentation of case We performed a retrospective review of patients who underwent liver transplantation between October 2015 and May 2020 to evaluate the efficiency of hydroxocobalamin in this setting. Discussion A total of 137 patients underwent liver transplantation, of which 20 received hydroxocobalamin for vasoplegia. Administration of hydroxocobalamin increased mean arterial pressure and reduced vasoactive drug requirements. Conclusion This case series adds to the previous individual reports describing the use of hydroxocobalamin during liver transplantation suggesting hydroxocobalamin can mitigate refractory hypotension from catecholamine resistant vasoplegia during liver transplantation.
Hypotension or vasoplegia is commonly encountered in end-stage liver disease. Vasoplegia during liver transplant is a common and potentially devastating condition. Hydroxocobalamin has been reported to improve catecholamine resistant vasoplegia. Hydroxocobalamin is believed to work by scavenging gasotransmitters NO, CO, and H2S.
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9
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Albertson TE, Chenoweth JA, Lewis JC, Pugashetti JV, Sandrock CE, Morrissey BM. The pharmacotherapeutic options in patients with catecholamine-resistant vasodilatory shock. Expert Rev Clin Pharmacol 2022; 15:959-976. [PMID: 35920615 DOI: 10.1080/17512433.2022.2110067] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB) and hydroxocobalamin can be added to maintain blood pressure. AREAS COVERED VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP. EXPERT OPINION Evidence supporting additional vasopressor agents in catecholamine resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor is used in VS to maintain adequate MAP. MB and/or hydoxocobalamin, vitamin C, thiamine and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given.
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Affiliation(s)
- Timothy E Albertson
- Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA.,Department of Emergency Medicine, University of California, Davis, Sacramento, CA, USA.,Department of Medicine, VA Northern California Health System, Mather, CA, USA.,Department of Clinical Pharmacy, University of California, San Francisco, CA, USA
| | - James A Chenoweth
- Department of Emergency Medicine, University of California, Davis, Sacramento, CA, USA.,Department of Medicine, VA Northern California Health System, Mather, CA, USA
| | - Justin C Lewis
- Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA.,Department of Clinical Pharmacy, University of California, San Francisco, CA, USA
| | - Janelle V Pugashetti
- Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA.,Department of Medicine, VA Northern California Health System, Mather, CA, USA
| | - Christian E Sandrock
- Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA.,Department of Medicine, VA Northern California Health System, Mather, CA, USA
| | - Brian M Morrissey
- Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA.,Department of Medicine, VA Northern California Health System, Mather, CA, USA
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10
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The Roles of Antidotes in Emergency Situations. Emerg Med Clin North Am 2022; 40:381-394. [DOI: 10.1016/j.emc.2022.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Bezinover D, Mukhtar A, Wagener G, Wray C, Blasi A, Kronish K, Zerillo J, Tomescu D, Pustavoitau A, Gitman M, Singh A, Saner FH. Hemodynamic Instability During Liver Transplantation in Patients With End-stage Liver Disease: A Consensus Document from ILTS, LICAGE, and SATA. Transplantation 2021; 105:2184-2200. [PMID: 33534523 DOI: 10.1097/tp.0000000000003642] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical causes of HDI, patient- and graft-related factors are also important. Nitric oxide-mediated vasodilatation is a common denominator associated with end-stage liver disease related to HDI. Despite intense investigation, optimal management strategies remain elusive. In this consensus article, experts from the International Liver Transplantation Society, the Liver Intensive Care Group of Europe, and the Society for the Advancement of Transplant Anesthesia performed a rigorous review of the most current literature regarding the epidemiology, causes, and management of HDI during LT. Special attention has been paid to unique LT-associated conditions including the causes and management of vasoplegic syndrome, cardiomyopathies, LT-related arrhythmias, right and left ventricular dysfunction, and the specifics of medical and fluid management in end-stage liver disease as well as problems specifically related to portal circulation. When possible, management recommendations are made.
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Affiliation(s)
- Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Pennsylvania State University, Penn State Health, Milton S. Hershey Medical Center, Hershey, PA. Represents ILTS and LICAGE
| | - Ahmed Mukhtar
- Department of Anesthesia and Surgical Intensive Care, Cairo University, Almanyal, Cairo, Egypt. Represents LICAGE
| | - Gebhard Wagener
- Department of Anesthesiology, Columbia University Medical Center, New York, NY. Represents SATA and ILTS
| | - Christopher Wray
- Department of Anesthesiology and Perioperative Medicine, University of California Los Angeles, Ronald Reagan Medical Center, Los Angeles, CA. Represents SATA
| | - Annabel Blasi
- Department of Anesthesia, IDIBAPS (Institut d´investigació biomèdica Agustí Pi i Sunyé) Hospital Clinic, Villaroel, Barcelona, Spain. Represents LICAGE and ILTS
| | - Kate Kronish
- Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA. Represents SATA
| | - Jeron Zerillo
- Department of Anesthesiology, Perioperative and Pain Medicine, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY. Represents SATA and ILTS
| | - Dana Tomescu
- Department of Anesthesiology and Intensive Care, Carol Davila University of Medicine and Pharmacy, Fundeni Clinical Institute, Bucharest, Romania. Represents LICAGE
| | - Aliaksei Pustavoitau
- Department of Anesthesia and Critical Care Medicine, Johns Hopkins Hospital, Johns Hopkins School of Medicine, Baltimore, MD. Represents ILTS
| | - Marina Gitman
- Department of Anesthesiology, University of Illinois Hospital, Chicago, IL. Represents SATA and ILTS
| | - Anil Singh
- Department of Liver Transplant and GI Critical Care, Sir HN Reliance Foundation Hospital, Cirgaon, Mumbai, India. Represents ILTS
| | - Fuat H Saner
- Department of General, Visceral and Transplant Surgery, Essen University Medical Center, Essen, Germany. Represents LICAGE
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12
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Gerdes HJ, Seelhammer TG, Nei S, Diaz Soto J, Nabzdyk CG. Extended Duration Infusion of Hydroxocobalamin for Vasoplegic Rescue in Septic Shock. Cureus 2021; 13:e13388. [PMID: 33754111 PMCID: PMC7971717 DOI: 10.7759/cureus.13388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Nitric oxide (NO) is a gaseous signaling molecule and a key endogenous mediator of vascular tone. Hydroxocobalamin (HCB) affects NO-mediated vasoplegia as (1) a direct inhibitor of nitric oxide synthase (NOS), thereby decreasing its production, and (2) by binding directly to NO and acting as a scavenger. HCB has been increasingly used in the treatment of refractory vasoplegia, particularly in cardiac surgery and liver transplant patients. Sepsis and septic shock are characterized by an increase in inducible NOS expression and activity with excessive NO production, resulting in endothelial dysfunction and profound systemic vasodilation. Therefore, a careful sustained reduction in NO burden represents a potential therapeutic target. Here, we present a case of refractory septic shock, which resolved after an extended duration infusion of high-dose HCB. We hope to foster further exploration regarding the safety, dosing, and efficacy of HCB when administered for vasopressor refractory septic shock.
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Affiliation(s)
- Harrison J Gerdes
- Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, USA
| | - Troy G Seelhammer
- Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, USA
| | - Scott Nei
- Pharmacy, Mayo Clinic, Rochester, USA
| | - Juan Diaz Soto
- Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, USA
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13
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Weinberg D, Running K, Kalarickal PL, Patel GP. Use of Intravenous Hydroxocobalamin for Vasoplegic Syndrome in Simultaneous Liver-Kidney Transplant: A Case Report. Transplant Proc 2020; 53:1300-1302. [PMID: 33246585 DOI: 10.1016/j.transproceed.2020.09.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/09/2020] [Accepted: 09/21/2020] [Indexed: 11/28/2022]
Abstract
Vasoplegic syndrome can occur after reperfusion in liver transplantation. Generally, vasopressor infusions along with volume resuscitation are used to combat this process. There are case reports of the use of hydroxocobalamin to improve vasoplegia in liver transplant and cardiac surgery. In this case report, we describe a patient who received hydroxocobalamin for a simultaneous liver-kidney transplant. Use of this medication facilitated a prompt decrease of very high-dose vasopressor infusions and allowed completion of the kidney transplantation portion of this case. To our knowledge, use in combined liver-kidney transplant has not been described. In light of the dearth of medications to improve vasoplegia outside of vasopressor infusions, the use of hydroxocobalamin as a therapeutic intervention may gain importance.
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Affiliation(s)
- Devin Weinberg
- Department of Anesthesiology, Emory University, Atlanta, Georgia
| | - Kati Running
- Department of Anesthesiology, Emory University, Atlanta, Georgia
| | | | - Gaurav P Patel
- Department of Anesthesiology, Emory University, Atlanta, Georgia.
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14
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Ayers B, Wood K, Falvey J, Bernstein W, Gosev I. The use of hydroxocobalamin for vasoplegic syndrome in left ventricular assist device patients. Clin Case Rep 2020; 8:1722-1727. [PMID: 32983485 PMCID: PMC7495745 DOI: 10.1002/ccr3.2967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 05/04/2020] [Accepted: 05/06/2020] [Indexed: 11/18/2022] Open
Abstract
We demonstrate evidence supporting the efficacy of hydroxocobalamin in reducing vasopressor requirements for LVAD patients with refractory vasoplegia. Further study is needed to substantiate these findings and determine its optimal use in practice.
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Affiliation(s)
- Brian Ayers
- Division of Cardiac SurgeryUniversity of Rochester Medical CenterRochesterNYUSA
| | - Katherine Wood
- Division of Cardiac SurgeryUniversity of Rochester Medical CenterRochesterNYUSA
| | | | - Wendy Bernstein
- Department of Anesthesiology and Perioperative MedicineUniversity of Rochester Medical CenterRochesterNYUSA
| | - Igor Gosev
- Division of Cardiac SurgeryUniversity of Rochester Medical CenterRochesterNYUSA
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15
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Kassel CA, Fremming BA, Brown BA, Markin NW. 2019 Clinical Update in Liver Transplantation. J Cardiothorac Vasc Anesth 2020; 35:1495-1502. [PMID: 32173208 DOI: 10.1053/j.jvca.2020.01.056] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 01/31/2020] [Indexed: 11/11/2022]
Abstract
Liver transplantation continues be the standard for treatment of end-stage liver disease, and even with recent advances in organ preservation, the anesthetic management continues to require understanding of multiple organ systems beyond the liver. Multiple factors contribute to hemodynamic changes after reperfusion of the liver graft that anesthesiologists should be aware of before unclamping. Concomitant renal dysfunction in end-stage liver disease is not uncommon, and preparation for continuous renal replacement therapy may need to be considered in certain cases. Cardiac evaluation of liver transplantation patients with an emphasis on arrhythmias, including atrial fibrillation, can help prevent both intraoperative and postoperative complications detrimental to the patient and graft. Finally, combined liver and thoracic organ transplantations may be indicated for certain disease processes that affect multiple organs. These cases require an understanding of the surgical technique and acknowledgment that some goals of the procedures may be in direct opposition to each other.
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16
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Busse LW, Barker N, Petersen C. Vasoplegic syndrome following cardiothoracic surgery-review of pathophysiology and update of treatment options. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2020; 24:36. [PMID: 32019600 PMCID: PMC7001322 DOI: 10.1186/s13054-020-2743-8] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 01/16/2020] [Indexed: 12/18/2022]
Abstract
Vasoplegic syndrome is a common occurrence following cardiothoracic surgery and is characterized as a high-output shock state with poor systemic vascular resistance. The pathophysiology is complex and includes dysregulation of vasodilatory and vasoconstrictive properties of smooth vascular muscle cells. Specific bypass machine and patient factors play key roles in occurrence. Research into treatment of this syndrome is limited and extrapolated primarily from that pertaining to septic shock, but is evolving with the expanded use of catecholamine-sparing agents. Recent reports demonstrate potential benefit in novel treatment options, but large clinical trials are needed to confirm.
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Affiliation(s)
- Laurence W Busse
- Department of Medicine, Emory University, Emory Critical Care Center, Atlanta, GA, USA. .,Emory Johns Creek Hospital, 6325 Hospital Parkway, Johns Creek, GA, 30097, USA.
| | - Nicholas Barker
- Department of Pharmacy, Emory St. Joseph's Hospital, Atlanta, GA, USA
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Manning MW, Kumar PA, Maheshwari K, Arora H. Post-Reperfusion Syndrome in Liver Transplantation—An Overview. J Cardiothorac Vasc Anesth 2020; 34:501-511. [DOI: 10.1053/j.jvca.2019.02.050] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 02/15/2019] [Accepted: 02/28/2019] [Indexed: 01/13/2023]
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18
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Del Rio JM, Twite M, Weitzel N, Kertai MD. Driving Paradigms Shifts Is at the Core of Our Specialty. Semin Cardiothorac Vasc Anesth 2019; 23:345-348. [PMID: 31690256 DOI: 10.1177/1089253219881833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- J Mauricio Del Rio
- Duke University, School of Medicine, Durham, NC, USA.,Duke University Medical Center, Durham, NC, USA
| | - Mark Twite
- Children's Hospital Colorado, Aurora, CO, USA.,University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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19
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Belletti A, Landoni G, Lomivorotov VV, Oriani A, Ajello S. Adrenergic Downregulation in Critical Care: Molecular Mechanisms and Therapeutic Evidence. J Cardiothorac Vasc Anesth 2019; 34:1023-1041. [PMID: 31839459 DOI: 10.1053/j.jvca.2019.10.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 09/09/2019] [Accepted: 10/10/2019] [Indexed: 02/08/2023]
Abstract
Catecholamines remain the mainstay of therapy for acute cardiovascular dysfunction. However, adrenergic receptors quickly undergo desensitization and downregulation after prolonged stimulation. Moreover, prolonged exposure to high circulating catecholamines levels is associated with several adverse effects on different organ systems. Unfortunately, in critically ill patients, adrenergic downregulation translates into progressive reduction of cardiovascular response to exogenous catecholamine administration, leading to refractory shock. Accordingly, there has been a growing interest in recent years toward use of noncatecholaminergic inotropes and vasopressors. Several studies investigating a wide variety of catecholamine-sparing strategies (eg, levosimendan, vasopressin, β-blockers, steroids, and use of mechanical circulatory support) have been published recently. Use of these agents was associated with improvement in hemodynamics and decreased catecholamine use but without a clear beneficial effect on major clinical outcomes. Accordingly, additional research is needed to define the optimal management of catecholamine-resistant shock.
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Affiliation(s)
- Alessandro Belletti
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Vladimir V Lomivorotov
- Department of Anesthesiology and Intensive Care, E. Meshalkin National Medical Research Center, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia
| | - Alessandro Oriani
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Silvia Ajello
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
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20
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21
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Vitamin B12 for the treatment of vasoplegia in cardiac surgery and liver transplantation: a narrative review of cases and potential biochemical mechanisms. Can J Anaesth 2019; 66:1501-1513. [DOI: 10.1007/s12630-019-01449-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 05/14/2019] [Accepted: 05/14/2019] [Indexed: 02/06/2023] Open
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22
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Patel JJ, Venegas-Borsellino C, Willoughby R, Freed JK. High-Dose Vitamin B12 in Vasodilatory Shock: A Narrative Review. Nutr Clin Pract 2019; 34:514-520. [PMID: 31187494 DOI: 10.1002/ncp.10327] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Vasodilatory shock, as observed in postoperative states and sepsis, is hallmarked by low systemic vascular resistance and low blood pressure compensated by increased cardiac output. Gasotransmitters, such as nitric oxide and hydrogen sulfide, are implicated in the development and perpetuation of vasodilatory shock. Established therapies do not target these physiologic drivers of vasodilation. Due to their nontoxic and pleotropic effects, micronutrients are being used as rescue therapy in postoperative vasoplegia and septic shock. Here, we outline the pathophysiology of vasodilatory shock, describe the rationale for vitamin B12 (hydroxocobalamin) in vasodilatory shock, and identify literature evaluating its use in vasoplegic states.
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Affiliation(s)
- Jayshil J Patel
- Division of Pulmonary & Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | - Rodney Willoughby
- Division of Pediatric Infectious Disease, Children's Hospital of Wisconsin and the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Julie K Freed
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.,Division of Cardiac Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA
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23
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Sakpal SV, Reedstrom H, Ness C, Klinkhammer T, Saucedo-Crespo H, Auvenshine C, Santella RN, Steers J. High-dose hydroxocobalamin in end-stage liver disease and liver transplantation. DRUGS & THERAPY PERSPECTIVES 2019; 35:442-446. [PMID: 32288505 PMCID: PMC7102271 DOI: 10.1007/s40267-019-00643-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Distributive shock is a serious complication in patients with chronic or end-stage liver disease, and can be exacerbated by vasoplegia in this patient population. Vasoplegic syndrome (VS) is a state of shock refractory to catecholamines and vasopressin that is often multifactorial in liver failure patients, and can occur in any phase of liver transplantation (LT) [i.e., pre-transplantation, intraoperative, and post-transplantation]. Methylene blue (MB) has been a well-established pharmacologic therapy for VS. However, it has been known to cause dose-related toxicity. Hydroxocobalamin (HXC) is not currently FDA approved for the management of VS, but studies have demonstrated its ability to cause an increase in systolic blood pressure by hypothesized mechanisms with only minimal side effects. To date, only three other reports have demonstrated the use of HXC in LT patients, which highlighted its use both intraoperatively and post-transplantation. Our report illustrates the utility of HXC in four LT patients with VS. Two of these cases illustrate the usefulness of HXC in the pre-transplantation period, which has never been previously reported. HXC is a useful pharmaceutical agent in the management of VS, especially if contraindications to MB exist or in cases of MB-resistant vasoplegia. Further studies with large sample sizes are necessary to ascertain the optimal dosage of HXC in LT patients.
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Affiliation(s)
- Sujit Vijay Sakpal
- 1Avera McKennan Hospital & University Health Center, Avera Medical Group Transplant & Liver Surgery, Plaza 3, 1315 S. Cliff Ave. Suite 1100, Sioux Falls, SD 57105 USA.,2Department of Surgery, University of South Dakota-Sanford School of Medicine, Sioux Falls, SD USA.,3Department of Internal Medicine, University of South Dakota-Sanford School of Medicine, Sioux Falls, SD USA
| | - Hannah Reedstrom
- 4Department of Pharmacy, Avera McKennan Hospital & University Health Center, Sioux Falls, SD USA
| | - Cody Ness
- 2Department of Surgery, University of South Dakota-Sanford School of Medicine, Sioux Falls, SD USA
| | - Tobin Klinkhammer
- 4Department of Pharmacy, Avera McKennan Hospital & University Health Center, Sioux Falls, SD USA
| | - Hector Saucedo-Crespo
- 1Avera McKennan Hospital & University Health Center, Avera Medical Group Transplant & Liver Surgery, Plaza 3, 1315 S. Cliff Ave. Suite 1100, Sioux Falls, SD 57105 USA.,2Department of Surgery, University of South Dakota-Sanford School of Medicine, Sioux Falls, SD USA
| | - Christopher Auvenshine
- 1Avera McKennan Hospital & University Health Center, Avera Medical Group Transplant & Liver Surgery, Plaza 3, 1315 S. Cliff Ave. Suite 1100, Sioux Falls, SD 57105 USA.,2Department of Surgery, University of South Dakota-Sanford School of Medicine, Sioux Falls, SD USA
| | - Robert N Santella
- 1Avera McKennan Hospital & University Health Center, Avera Medical Group Transplant & Liver Surgery, Plaza 3, 1315 S. Cliff Ave. Suite 1100, Sioux Falls, SD 57105 USA.,3Department of Internal Medicine, University of South Dakota-Sanford School of Medicine, Sioux Falls, SD USA
| | - Jeffery Steers
- 1Avera McKennan Hospital & University Health Center, Avera Medical Group Transplant & Liver Surgery, Plaza 3, 1315 S. Cliff Ave. Suite 1100, Sioux Falls, SD 57105 USA
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Feih JT, Rinka JR, Zundel MT. Methylene Blue Monotherapy Compared With Combination Therapy With Hydroxocobalamin for the Treatment of Refractory Vasoplegic Syndrome: ARetrospective Cohort Study. J Cardiothorac Vasc Anesth 2019; 33:1301-1307. [DOI: 10.1053/j.jvca.2018.11.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Indexed: 11/11/2022]
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25
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Shapeton AD, Mahmood F, Ortoleva JP. Hydroxocobalamin for the Treatment of Vasoplegia: A Review of Current Literature and Considerations for Use. J Cardiothorac Vasc Anesth 2019; 33:894-901. [DOI: 10.1053/j.jvca.2018.08.017] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Indexed: 12/15/2022]
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26
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An SS, Henson CP, Freundlich RE, McEvoy MD. Case report of high-dose hydroxocobalamin in the treatment of vasoplegic syndrome during liver transplantation. Am J Transplant 2018; 18:1552-1555. [PMID: 29573551 PMCID: PMC6138872 DOI: 10.1111/ajt.14736] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 03/02/2018] [Accepted: 03/08/2018] [Indexed: 01/25/2023]
Abstract
A 66-year-old man with cryptogenic cirrhosis secondary to nonalcoholic steatohepatitis presented for orthotopic liver transplantation. Following organ reperfusion, the patient developed vasoplegic syndrome, with arterial blood pressures of approximately 60-70/30-40 mm Hg (mean arterial pressure [MAP] <45 mm Hg) for >90 minutes. He required high-dose norepinephrine and vasopressin infusions, as well as i.v. bolus doses of norepinephrine and vasopressin to reach a goal MAP> 60 mm Hg. There was minimal response to a 2 mg/kg i.v. bolus of methylene blue. Following the administration of 5 g of i.v.hydroxocobalamin, the patient had a profound improvement in arterial blood pressure, with subsequent discontinuation of the vasopressin infusion and rapid reduction of norepinephrine infusion from 20 to 2 μg/min. While there have been several reports of the efficacy of hydroxocobalamin for vasoplegia after cardiopulmonary bypass, there have been only limited cases of hydroxocobalamin used in liver transplantation, and none with high-dose administration. We present a case of vasoplegic syndrome during liver transplantation that was refractory to high-dose vasopressors and methylene blue but responsive to high-dose i.v. hydroxocobalamin.
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Affiliation(s)
- S. Sandy An
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - C. Patrick Henson
- Division of Critical Care, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Robert E. Freundlich
- Division of Critical Care, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Matthew D. McEvoy
- Department of Anesthesiology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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Zundel MT, Feih JT, Rinka JR, Boettcher BT, Freed JK, Kaiser M, Ghadiali HY, Tawil JN, Woehlck HJ, Pagel PS. Hydroxocobalamin With or Without Methylene Blue May Improve Fluid Balance in Critically Ill Patients With Vasoplegic Syndrome After Cardiac Surgery: A Report of Two Cases. J Cardiothorac Vasc Anesth 2018; 32:452-457. [DOI: 10.1053/j.jvca.2017.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Indexed: 11/11/2022]
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28
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Shah PR, Reynolds PS, Pal N, Tang D, McCarthy H, Spiess BD. Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: a case series. Can J Anaesth 2017; 65:560-568. [DOI: 10.1007/s12630-017-1029-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 10/30/2017] [Accepted: 10/30/2017] [Indexed: 10/18/2022] Open
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29
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