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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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Bækgaard ES, Madsen BK, Crone V, El-Hallak H, Møller MH, Vester-Andersen M, Krag M. Perioperative hypotension and use of vasoactive agents in non-cardiac surgery: A scoping review. Acta Anaesthesiol Scand 2024; 68:1134-1148. [PMID: 38965670 DOI: 10.1111/aas.14485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/03/2024] [Accepted: 06/13/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND Perioperative hypotension is common and associated with adverse patient outcomes. Vasoactive agents are often used to manage hypotension, but the ideal drug, dose and duration of treatment has not been established. With this scoping review, we aim to provide an overview of the current body of evidence regarding the vasoactive agents used to treat perioperative hypotension in non-cardiac surgery. METHODS We included all studies describing the use of vasoactive agents for the treatment of perioperative hypotension in non-cardiac surgery. We excluded literature reviews, case studies, and studies on animals and healthy subjects. We posed the following research questions: (1) in which surgical populations have vasoactive agents been studied? (2) which agents have been studied? (3) what doses have been assessed? (4) what is the duration of treatment? and (5) which desirable and undesirable outcomes have been assessed? RESULTS We included 124 studies representing 10 surgical specialties. Eighteen different agents were evaluated, predominantly phenylephrine, ephedrine, and noradrenaline. The agents were administered through six different routes, and numerous comparisons between agents, dosages and routes were included. Then, 88 distinct outcome measures were assessed, of which 54 were judged to be non-patient-centred. CONCLUSIONS We found that studies concerning vasoactive agents for the treatment of perioperative hypotension varied considerably in all aspects. Populations were heterogeneous, interventions and exposures included multiple agents compared against themselves, each other, fluids or placebo, and studies reported primarily non-patient-centred outcomes.
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Affiliation(s)
| | - Bennedikte Kollerup Madsen
- Department of Anaesthesiology and Intensive Care, Holbæk Hospital, Holbæk, Denmark
- Department of Anaesthesiology and Intensive Care, Zealand University Hospital, Køge, Denmark
| | - Vera Crone
- Department of Anaesthesiology and Intensive Care, Holbæk Hospital, Holbæk, Denmark
| | - Hayan El-Hallak
- Department of Anaesthesiology and Intensive Care, Holbæk Hospital, Holbæk, Denmark
- Department of Anaesthesiology, Copenhagen University Hospital-Gentofte, Hellerup, Denmark
| | - Morten Hylander Møller
- Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Morten Vester-Andersen
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Anaesthesiology and Intensive Care, Copenhagen University Hospital-Herlev-Gentofte, Herlev, Denmark
| | - Mette Krag
- Department of Anaesthesiology and Intensive Care, Holbæk Hospital, Holbæk, Denmark
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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González-Suárez S, Serrano HA, Chocron IZ, Tormos P, Cano E, Galán P, de Nadal M, Matarín S, Cabeza M, Rodríguez-Tesouro AB. Postreperfusion Syndrome in Patients Receiving Vasoactive Drugs During Liver Graft Reperfusion. EXP CLIN TRANSPLANT 2024; 22:43-51. [PMID: 38284374 DOI: 10.6002/ect.2023.0146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2024]
Abstract
OBJECTIVES The most widely used definition of postreperfusion syndrome in liver transplant is a 30% decrease in mean arterial pressure during the first 5 minutes after vascular unclamping. With these criteria, increased postoperative morbidity has been reported. Vasoactivedrugs couldpreventthis syndrome.Themain objective of our study was to determine the incidence and complications associated with postreperfusion syndrome inpatientswho receivedvasoactive support. MATERIALS AND METHODS We studied 246 patients who received norepinephrine infusions to maintain mean arterial pressure ≥60 mm Hg and who were monitored with a Swan-Ganz catheter. Patients received a bolus of adrenaline after vascular unclamping in cases of insufficient response to norepinephrine. RESULTS Among the study patients, 57 (23.17%) developed postreperfusion syndrome. Patients who developed postreperfusion syndrome did not present with morepostoperative complications interms ofrenal dysfunction (P = .69), repeat surgery (P = .15), graft rejection (P = .69), transplant replacement surgery (P = .76), hospital stay (P = .70), or survival (P = .17) compared with patients without postreperfusion syndrome. CONCLUSIONS In patients who underwent orthotopic liver transplant, in whom vasoactive drugs were administered, a diagnosis of self-limited postreperfusion syndrome during the first 5 minutes after unclamping may not be associated with postoperative complications. The administration of vasoconstrictors may have a preventive effect on the postoperative complications associated with postreperfusion syndrome or they may mask the real incidence of postreperfusion syndrome. A broader definition of postreperfusion syndrome should be accepted.
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Affiliation(s)
- Susana González-Suárez
- From the Department of Surgery, Universitat Autònoma de Barcelona, Unitat Docent Vall d'Hebron, Barcelona, Spain; and the Department of Anesthesiology and Intensive Care, Vall d'Hebron University Hospital, Barcelona, Spain
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Intraoperative dialysis with the use of a mobile dialysis system during liver transplantation. Adv Med Sci 2022; 67:208-215. [PMID: 35568010 DOI: 10.1016/j.advms.2022.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 03/22/2022] [Accepted: 04/29/2022] [Indexed: 11/23/2022]
Abstract
PURPOSE Over the last few years, transplant centers have started to use various intraoperative renal replacement therapy (ioRRT) modalities during liver transplantation (LT) in patients with pre-existing renal impairment. Here, we present a study on the safety and clinical outcomes of intraoperative hemodialysis (ioHD) performed using a mobile dialysis system during LT. PATIENTS AND METHODS We retrospectively analyzed 102 adult patients undergoing LT with ioHD; pre-existing renal failure and/or intraoperative metabolic derangement were ioHD treatment indications. RESULTS Our study cohort consisted of three groups: LT with preoperative serum creatinine (sCr) < 2 mg/dL (Group 1:n = 22), LT with preoperative sCr ≥2 mg/dL (Group 2:n = 73), and simultaneous liver-kidney transplantation (Group 3:n = 7). Among the procedures, 30% were re-transplantations. The mean calculated Model for End-stage Liver Disease score in Group 2 was 39.2, and 67% of patients were hospitalized in the intensive care unit. Patients in Group 1 were less acutely ill but developed severe intraoperative derangements and, therefore, underwent urgent ioHD intraoperatively. However, it was delayed when compared to Group 2. All groups achieved post-reperfusion potassium levels <4 mmol/L and a decrease in central venous pressure. No serious procedural complications occurred. Post-reperfusion syndrome occurred in 12.7% of patients. Elevated mortality was likely due to the high illness severity in the cohort. CONCLUSIONS Performing ioHD with a mobile dialysis system during LT was safe and effective, while being easier to perform than continuous techniques. Its effect on intra- and postoperative outcomes should be addressed in a study with a control group.
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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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Kościelska M, Matuszkiewicz-Rowińska J, Zieniewicz K, Krawczyk M, Giercuszkiewicz D, Sierdziński J, Żebrowski P, Małyszko J. Intraoperative Dialysis During Liver Transplantation. Transplant Proc 2020; 52:2454-2458. [PMID: 32448654 DOI: 10.1016/j.transproceed.2020.01.129] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 01/26/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Orthotopic liver transplantation (LT) is a technically complex surgical procedure associated with a major risk of hemodynamic instability and metabolic derangement, especially in patients with coexisting renal dysfunction. Some centers have applied intraoperative renal replacement therapy (ioRRT) to support patients with preoperative renal failure and prevent critical complications. Although there is a strong theoretical rationale for this treatment, there remains a paucity of definite data demonstrating its benefits. METHODS This was a retrospective observational study of all adult patients undergoing intraoperative dialysis in our center from January 2010 till December 2016. RESULTS The study group consisted of 88 patients with a mean MELD score of 31.4. Six patients underwent simultaneous liver and kidney transplantation. Forty-four (50%) recipients were admitted to the intensive care unit before transplantation, and 19 (21.6%) needed mechanical ventilation. Twenty-eight (31.8%) of the procedures were retransplantations, and 40 (45.4%) patients had been undergoing renal replacement therapy before LT. The mean preoperative serum creatinine was 2.82 ± 1.13 mg/dL. The majority of patients (54.5%) was operated on using the veno-venous bypass technique. The mean arterial blood pH and potassium levels after reperfusion were 7.2 ± 0.12 and 4.04 ± 0.95 mmol/L, respectively. Postreperfusion syndrome (PRS) occurred in 11 (13.9%) patients in whom dialysis started at least 15 minutes before reperfusion. Dialysis circuit clotting occurred in 9.1% of cases. There were no other adverse events of ioRRT. CONCLUSION Our data suggests that intraoperative dialysis in severely ill patients with a high MELD score is safe and effective. Lower than expected PRS occurrence needs to be confirmed in a study with a control group.
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Affiliation(s)
- Małgorzata Kościelska
- Department of Nephrology, Dialysis, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
| | | | - Krzysztof Zieniewicz
- Department of General, Liver, and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Marek Krawczyk
- Department of General, Liver, and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Dorota Giercuszkiewicz
- Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
| | - Janusz Sierdziński
- Department of Medical Informatics and Telemedicine, Medical University of Warsaw, Warsaw, Poland
| | - Paweł Żebrowski
- Department of Nephrology, Dialysis, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Jolanta Małyszko
- Department of Nephrology, Dialysis, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
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Anaesthesia for Liver Transplantation: An Update. ACTA ACUST UNITED AC 2020; 6:91-100. [PMID: 32426515 PMCID: PMC7216023 DOI: 10.2478/jccm-2020-0011] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 01/30/2020] [Indexed: 02/07/2023]
Abstract
Liver transplantation (LT) is a challenging surgery performed on patients with complex physiology profiles, complicated by multi-system dysfunction. It represents the treatment of choice for end-stage liver disease. The procedure is performed under general anaesthesia, and a successful procedure requires an excellent understanding of the patho-physiology of liver failure and its implications. Despite advances in knowledge and technical skills and innovations in immunosuppression, the anaesthetic management for LT can be complicated and represent a real challenge. Monitoring devices offer crucial information for the successful management of patients. Hemodynamic instability is typical during surgery, requiring sophisticated invasive monitoring. Arterial pulse contour analysis and thermo-dilution techniques (PiCCO), rotational thromboelastometry (RO-TEM), transcranial doppler (TCD), trans-oesophageal echocardiography (TEE) and bispectral index (BIS) have been proven to be reliable monitoring techniques playing a significant role in decision making. Anaesthetic management is specific according to the three critical phases of surgery: pre-anhepatic, anhepatic and neo-hepatic phase. Surgical techniques such as total or partial clamping of the inferior vena cava (IVC), use of venovenous bypass (VVBP) or portocaval shunts have a significant impact on cardiovascular stability. Post reperfusion syndrome (PRS) is a significant event and can lead to arrhythmias and even cardiac arrest.
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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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Kaufmann T, Clement RP, Scheeren TWL, Saugel B, Keus F, Horst ICC. Perioperative goal-directed therapy: A systematic review without meta-analysis. Acta Anaesthesiol Scand 2018; 62:1340-1355. [PMID: 29978454 DOI: 10.1111/aas.13212] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 06/03/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Perioperative goal-directed therapy aims to optimise haemodynamics by titrating fluids, vasopressors and/or inotropes to predefined haemodynamic targets. Perioperative goal-directed therapy is a complex intervention composed of several independent component interventions. Trials on perioperative goal-directed therapy show conflicting results. We aimed to conduct a systematic review and meta-analysis to investigate the benefits and harms of perioperative goal-directed therapy. METHODS PubMED, EMBASE, Web of Science and Cochrane Library were searched. Trials were included if they had a perioperative goal-directed therapy protocol. The primary outcome was all-cause mortality. The first secondary outcome was serious adverse events excluding mortality. Risk of bias was assessed, and GRADE was used to evaluate quality of evidence. RESULTS One hundred and twelve randomised trials were included of which one trial (1%) had low risk of bias. Included trials varied in patients: types of surgery which was expected due to inclusion criteria; in intervention and comparison: timing of intervention, monitoring devices, haemodynamic variables, target values, use of fluids, vasopressors and/or inotropes as well as combinations of these within protocols; and in outcome: mortality was reported in 87 trials (78%). Due to substantial clinical heterogeneity also within the various types of surgery a meta-analysis of data, including subgroup analyses, as defined in our protocol was considered inappropriate. CONCLUSION Clinical heterogeneity in patients, interventions and outcomes in perioperative goal-directed therapy trials is too large to perform meta-analysis on all trials. Future trials and meta-analyses highly depend on universally agreed definitions on aspects beyond type of surgery of the complex intervention and its evaluation.
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Affiliation(s)
- Thomas Kaufmann
- Department of Anesthesiology University Medical Center Groningen University of Groningen Groningen The Netherlands
| | - Ramon P. Clement
- Department of Anesthesiology University Medical Center Groningen University of Groningen Groningen The Netherlands
| | - Thomas W. L. Scheeren
- Department of Anesthesiology University Medical Center Groningen University of Groningen Groningen The Netherlands
| | - Bernd Saugel
- Department of Anesthesiology University Medical Center Hamburg‐Eppendorf Hamburg Germany
| | - Frederik Keus
- Department of Critical Care University Medical Center Groningen University of Groningen Groningen The Netherlands
| | - Iwan C. C. Horst
- Department of Critical Care University Medical Center Groningen University of Groningen Groningen The Netherlands
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Fayed NA, Sayed EI, Saleh SM, Ehsan NA, Elfert AY. Effect of dexmedetomidine on hepatic ischemia-reperfusion injury in the setting of adult living donor liver transplantation. Clin Transplant 2016; 30:470-82. [DOI: 10.1111/ctr.12713] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2016] [Indexed: 12/14/2022]
Affiliation(s)
- Nirmeen A. Fayed
- Anesthesia and Intensive Care; National Liver Institute; Menoufia University; ShebeenAlkoom Menoufia Egypt
| | - Eman I. Sayed
- Anesthesia and Intensive Care; National Liver Institute; Menoufia University; ShebeenAlkoom Menoufia Egypt
| | - Sherif M. Saleh
- Hepatobiliary Surgery; National Liver Institute; Menoufia University; ShebeenAlkoom Menoufia Egypt
| | - Nermen A. Ehsan
- Pathology; National Liver Institute; Menoufia University; ShebeenAlkoom Menoufia Egypt
| | - Ashraf Y. Elfert
- Clinical Biochemistry; National Liver Institute; Menoufia University; ShebeenAlkoom Menoufia Egypt
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Siniscalchi A, Gamberini L, Laici C, Bardi T, Ercolani G, Lorenzini L, Faenza S. Post reperfusion syndrome during liver transplantation: From pathophysiology to therapy and preventive strategies. World J Gastroenterol 2016; 22:1551-1569. [PMID: 26819522 PMCID: PMC4721988 DOI: 10.3748/wjg.v22.i4.1551] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 10/20/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, “Reperfusion” AND “liver transplantation” were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies.
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