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Volberg C, Toussaint K, Politt K, Gschnell M, Wulf H. [Cancer Treatment and Anaesthesia - What are the Perioperative Considerations?]. Anasthesiol Intensivmed Notfallmed Schmerzther 2025; 60:229-242. [PMID: 40233784 DOI: 10.1055/a-2442-5977] [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: 04/17/2025]
Abstract
Modern oncological treatment options are significantly extending patient survival. As a result, anaesthetists are increasingly faced with patients who have been pre-treated with immunotherapy or chemotherapy, are currently undergoing a cycle of therapy, or even need to receive chemotherapy intraoperatively. As the anaesthetic agents and perioperative analgesics may interfere with the oncological drugs, it is of interest for the anaesthetist to be aware of the spectrum of side effects and incompatibilities and to adapt the anaesthetic and perioperative treatment regimens accordingly. The aim of this review article is to present the relevant information and provide the clinician with recommendations on where problems may occur and how they can be avoided.
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Bezu L, Akçal Öksüz D, Bell M, Buggy D, Diaz-Cambronero O, Enlund M, Forget P, Gupta A, Hollmann MW, Ionescu D, Kirac I, Ma D, Mokini Z, Piegeler T, Pranzitelli G, Smith L, The EuroPeriscope Group. Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review. Cancers (Basel) 2024; 16:2304. [PMID: 39001366 PMCID: PMC11240822 DOI: 10.3390/cancers16132304] [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] [Received: 05/18/2024] [Revised: 06/19/2024] [Accepted: 06/20/2024] [Indexed: 07/16/2024] Open
Abstract
Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics' impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature.
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Affiliation(s)
- Lucillia Bezu
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Département d'Anesthésie, Chirurgie et Interventionnel, Gustave Roussy, 94805 Villejuif, France
- U1138 Metabolism, Cancer and Immunity, Gustave Roussy, 94805 Villejuif, France
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA
| | - Dilara Akçal Öksüz
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Clinic for Anesthesiology, Intensive Care, Emergency Medicine, Pain Therapy and Palliative Medicine, Marienhaus Klinikum Hetzelstift, 67434 Neustadt an der Weinstrasse, Germany
- ESAIC Mentorship Program, BE-1000 Brussels, Belgium
| | - Max Bell
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Perioperative Medicine and Intensive Care (PMI), Karolinska University Hospital, Solna, 17176 Stockholm, Sweden
- Department of Physiology and Pharmacology, Karolinska Institute, 17176 Stockholm, Sweden
| | - Donal Buggy
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Division of Anaesthesiology, Mater Misericordiae University Hospital, D07 WKW8 Dublin, Ireland
- School of Medicine, University College, D04 V1W8 Dublin, Ireland
| | - Oscar Diaz-Cambronero
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Anesthesiology, Hospital Universitario y Politécnico la Fe, 46026 Valencia, Spain
- Perioperative Medicine Research, Health Research Institute Hospital la Fe, 46026 Valencia, Spain
- Faculty of Medicine, Department of Surgery, University of Valencia, 46010 Valencia, Spain
| | - Mats Enlund
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Center for Clinical Research, Uppsala University, SE-72189 Västerås, Sweden
- Department of Anesthesia & Intensive Care, Västmanland Hospital, SE-72189 Västerås, Sweden
| | - Patrice Forget
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Aberdeen Centre for Arthritis and Musculoskeletal Health (Epidemiology Group), Institute of Applied Health Sciences, Epidemiology Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZN, UK
- Department of Anaesthesia, NHS Grampian, University of Aberdeen, Aberdeen AB25 2ZN, UK
- Pain and Opioids after Surgery (PANDOS) ESAIC Research Group, European Society of Anaesthesiology and Intensive Care, 1000 Brussels, Belgium
- IMAGINE UR UM 103, Anesthesia Critical Care, Emergency and Pain Medicine Division, Nîmes University Hospital, Montpellier University, 30900 Nîmes, France
| | - Anil Gupta
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Physiology and Pharmacology, Karolinska Institute, 17176 Stockholm, Sweden
| | - Markus W Hollmann
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Anesthesiology, Amsterdam UMC, 1100 DD Amsterdam, The Netherlands
| | - Daniela Ionescu
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Anesthesia and Intensive Care, University of Medicine and Pharmacy "Iuliu Hatieganu", 400012 Cluj-Napoca, Romania
- Outcome Research Consortium, Cleveland, OH 44195, USA
| | - Iva Kirac
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Genetic Counselling Unit, University Hospital for Tumors, Sestre Milosrdnice University Hospital Centre, 10000 Zagreb, Croatia
| | - Daqing Ma
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London SW10 9NH, UK
- Department of Anesthesiology, Perioperative and Systems Medicine Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
| | - Zhirajr Mokini
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- ESAIC Mentorship Program, BE-1000 Brussels, Belgium
- Clinique du Pays de Seine, 77590 Bois le Roi, France
| | - Tobias Piegeler
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Anesthesiology and Intensive Care, University of Leipzig Medical Center, 04275 Leipzig, Germany
| | - Giuseppe Pranzitelli
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Anesthesiology and Intensive Care, San Timoteo Hospital, 86039 Termoli, Italy
| | - Laura Smith
- EuroPeriscope, ESA-IC Onco-Anaesthesiology Research Group, B-1000 Brussels, Belgium
- Department of Anaesthesia, NHS Grampian, University of Aberdeen, Aberdeen AB25 2ZN, UK
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZN, UK
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Koutsogiannaki S, Wang W, Hou L, Okuno T, Yuki K. Mechanism of isoflurane‑mediated breast cancer growth in vivo. Oncol Lett 2024; 27:287. [PMID: 38736741 PMCID: PMC11083926 DOI: 10.3892/ol.2024.14420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/23/2024] [Indexed: 05/14/2024] Open
Abstract
Use of volatile anesthetics is associated with worse outcome following tumor resection surgery compared with the use of intravenous anesthetics. However, the underlying mechanism has not been clearly delineated yet in vivo. The EO771 cell-based congenic breast cancer model was used in the present study. Isoflurane directly binds to and inhibits two adhesion molecules, leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1). Similarly, exposure to sevoflurane, another volatile anesthetic and LFA-1 inhibitor, is associated with an increase in breast cancer size compared with non-exposure. Thus, the present study first examined the role of LFA-1 and Mac-1 in the EO771 breast cancer model. Both LFA-1 deficiency and inhibition enhanced tumor growth, which was supported by cytokine and eicosanoid data profiles. By contrast, Mac-1 deficiency did not affect tumor growth. The exposure to isoflurane and sevoflurane was associated with an increase in breast cancer size compared with non-exposure. These data suggested that isoflurane enhanced tumor growth by interacting with LFA-1. Isoflurane exposure did not affect tumor growth in LFA-1-deficient mice. In summary, the present data showed that LFA-1 deficiency facilitated breast cancer growth, and isoflurane, an LFA-1 inhibitor, also increased breast cancer growth.
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Affiliation(s)
- Sophia Koutsogiannaki
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, MA 02115, USA
- Department of Anaesthesia and Immunology, Harvard Medical School, Boston, MA 02115, USA
| | - Wei Wang
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, MA 02115, USA
| | - Lifei Hou
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, MA 02115, USA
- Department of Anaesthesia and Immunology, Harvard Medical School, Boston, MA 02115, USA
| | - Toshiaki Okuno
- Department of Biochemistry, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
| | - Koichi Yuki
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, MA 02115, USA
- Department of Anaesthesia and Immunology, Harvard Medical School, Boston, MA 02115, USA
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Maisat W, Yuki K. Narrative review of systemic inflammatory response mechanisms in cardiac surgery and immunomodulatory role of anesthetic agents. Ann Card Anaesth 2023; 26:133-142. [PMID: 37706376 PMCID: PMC10284469 DOI: 10.4103/aca.aca_147_22] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 12/05/2022] [Accepted: 12/18/2022] [Indexed: 09/15/2023] Open
Abstract
Although surgical techniques and perioperative care have made significant advances, perioperative mortality in cardiac surgery remains relatively high. Single- or multiple-organ failure remains the leading cause of postoperative mortality. Systemic inflammatory response syndrome (SIRS) is a common trigger for organ injury or dysfunction in surgical patients. Cardiac surgery involves major surgical dissection, the use of cardiopulmonary bypass (CPB), and frequent blood transfusions. Ischemia-reperfusion injury and contact activation from CPB are among the major triggers for SIRS. Blood transfusion can also induce proinflammatory responses. Here, we review the immunological mechanisms of organ injury and the role of anesthetic regimens in cardiac surgery.
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Affiliation(s)
- Wiriya Maisat
- Division of Cardiac Anesthesia, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, USA
- Department of Anaesthesia, Harvard Medical School, Boston, USA
- Department of Immunology, Harvard Medical School, Boston, USA
- Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Koichi Yuki
- Division of Cardiac Anesthesia, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, USA
- Department of Anaesthesia, Harvard Medical School, Boston, USA
- Department of Immunology, Harvard Medical School, Boston, USA
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Ramirez MF, Cata JP. Anesthetic care influences long-term outcomes: What is the evidence? Best Pract Res Clin Anaesthesiol 2021; 35:491-505. [PMID: 34801212 DOI: 10.1016/j.bpa.2021.01.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 01/27/2021] [Indexed: 10/22/2022]
Abstract
Despite advances in cancer therapy surgery remains one of the most important treatments for solid tumors; however, even with the development of better and less invasive surgical techniques, surgery is characterized by the increased risk of tumor metastasis, accelerated growth of pre-existing micrometastasis and cancer recurrence. Total intravenous anesthesia (TIVA) and regional anesthesia have been proposed to improve long-term outcomes after cancer surgery by different mechanisms, including attenuation of the neuroendocrine response, immunosuppression, decreased opioid requirements (opioids promote angiogenesis and tumor growth) and avoidance of volatile inhalational agents. Much of the data that support these ideas originate from laboratory studies, while there is no clear consensus from the retrospective cohort studies to date. Several randomized controlled trials (RCTs) are in progress and may provide a better understanding regarding the role of the anesthesiologist in cancer surgery. The purpose of this review is to summarize the experimental and human data regarding the effect of anesthesia agents and anesthesia techniques on cancer outcomes.
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Affiliation(s)
- M F Ramirez
- Department of Anesthesiology and Perioperative Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA; Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA
| | - J P Cata
- Department of Anesthesiology and Perioperative Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA; Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA.
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The Role of General Anesthetic Drug Selection in Cancer Outcome. BIOMED RESEARCH INTERNATIONAL 2021; 2021:2563093. [PMID: 34660784 PMCID: PMC8516539 DOI: 10.1155/2021/2563093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 09/30/2021] [Indexed: 01/07/2023]
Abstract
Cancer remains to be the leading cause of death globally. Surgery is a mainstay treatment for solid tumors. Thus, it is critical to optimize perioperative care. Anesthesia is a requisite component for surgical tumor resection, and general anesthesia is given in the vast majority of tumor resection cases. Because anesthetics are growingly recognized as immunomodulators, it is critical to optimize anesthetic regimens for cancer surgery if the selection can affect outcomes. Here, we reviewed the role of volatile and intravenous anesthesia used for cancer surgery in cancer recurrence.
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Fan Y, Yu D, Liang X. Volatile anesthetics versus intravenous anesthetics for noncardiac thoracic surgery: a systematic review and meta-analysis. Minerva Anestesiol 2021; 87:927-939. [PMID: 33938675 DOI: 10.23736/s0375-9393.21.15135-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION We performed this meta-analysis of randomised controlled trials (RCTs) to investigate two types of anesthetics for noncardiac thoracic surgery regarding their effects on clinical outcomes and the inflammatory response. EVIDENCE ACQUISITION We searched Cochrane Library, PubMed and EMBASE for RCTs comparing volatile anesthetics to intravenous anesthetics for noncardiac thoracic surgery. EVIDENCE SYNTHESIS This study reviewed 16 RCTs with 1467 patients. Volatile anesthetics reduced postoperative complications and the length of intensive care unit stay for lung surgery. They also lowered the concentrations of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor-α (TNF-α) in the airways of patients undergoing noncardiac thoracic surgery. However, there was no difference in short-term mortality; postoperative complications after esophagectomy; IL-1β, IL-6, IL-8 or TNF-α concentrations in the blood; IL-10 level in either the airway or the blood; overall monocyte chemoattractant protein-1. CONCLUSIONS In lung surgery, but not esophagectomy, volatile anesthetics may be a better choice than intravenous anesthetics, possibly because volatile anesthetics reduce airway inflammation.
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Affiliation(s)
- Yuchao Fan
- Department of Anesthesiology, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Deshui Yu
- Department of Anesthesiology, The Second People's Hospital of Yibin, Yibin, China
| | - Xiao Liang
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China -
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Surgical Site Infections and Perioperative Optimization of Host Immunity by Selection of Anesthetics. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5576959. [PMID: 33763473 PMCID: PMC7963902 DOI: 10.1155/2021/5576959] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/22/2021] [Accepted: 03/05/2021] [Indexed: 11/17/2022]
Abstract
Surgical site infections are significant health care issues, and efforts to mitigate their occurrence have been ongoing worldwide, mainly focusing to reduce the spillage of microbes to the otherwise sterile tissues. Optimization of host immunity has been also recognized including temperature regulation (normothermia), adequate oxygenation, and glucose management. A number of papers have described the role of anesthetics in host immunity. The role of anesthetics in postoperative outcomes including surgical site infections has been also studied. We will review the current literature and propose the importance of anesthetic selection to potentially mitigate surgical site infections.
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Nieuwenhuijs-Moeke GJ, Bosch DJ, Leuvenink HG. Molecular Aspects of Volatile Anesthetic-Induced Organ Protection and Its Potential in Kidney Transplantation. Int J Mol Sci 2021; 22:ijms22052727. [PMID: 33800423 PMCID: PMC7962839 DOI: 10.3390/ijms22052727] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/25/2021] [Accepted: 03/03/2021] [Indexed: 12/16/2022] Open
Abstract
Ischemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively impacts graft and patient outcome. Reperfusion takes place in the recipient and most of the injury following ischemia and reperfusion occurs during this reperfusion phase; therefore, the intra-operative period seems an attractive window of opportunity to modulate IRI and improve short- and potentially long-term graft outcome. Commonly used volatile anesthetics such as sevoflurane and isoflurane have been shown to interfere with many of the pathophysiological processes involved in the injurious cascade of IRI. Therefore, volatile anesthetic (VA) agents might be the preferred anesthetics used during the transplantation procedure. This review highlights the molecular and cellular protective points of engagement of VA shown in in vitro studies and in vivo animal experiments, and the potential translation of these results to the clinical setting of kidney transplantation.
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Affiliation(s)
- Gertrude J. Nieuwenhuijs-Moeke
- Department of Anesthesiology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
- Correspondence: ; Tel.: +31-631623075
| | - Dirk J. Bosch
- Department of Anesthesiology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
| | - Henri G.D. Leuvenink
- Department of Surgery, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
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Yuki K, Hou L, Shibamura-Fujiogi M, Koutsogiannaki S, Soriano SG. Mechanistic consideration of the effect of perioperative volatile anesthetics on phagocytes. Clin Immunol 2021; 222:108635. [PMID: 33217544 PMCID: PMC7856197 DOI: 10.1016/j.clim.2020.108635] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 11/12/2020] [Accepted: 11/14/2020] [Indexed: 02/06/2023]
Abstract
A growing literature has shown that volatile anesthetics are promiscuous molecules targeting multiple molecules, some of which are critical for immunological functions. We focused on studies that delineated target molecules of volatile anesthetics on immune cells and summarized the effects of volatile anesthetics on immune functions. We also presented the perspectives of studying volatile anesthetics-mediated immunomodulation.
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Affiliation(s)
- Koichi Yuki
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
| | - Lifei Hou
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
| | - Miho Shibamura-Fujiogi
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
| | - Sophia Koutsogiannaki
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
| | - Sulpicio G Soriano
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA.
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Meng XY, Zhang XP, Sun Z, Wang HQ, Yu WF. Distant survival for patients undergoing surgery using volatile versus IV anesthesia for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study. BMC Anesthesiol 2020; 20:233. [PMID: 32928121 PMCID: PMC7491163 DOI: 10.1186/s12871-020-01111-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 07/28/2020] [Indexed: 12/16/2022] Open
Abstract
Background Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.
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Affiliation(s)
- Xiao-Yan Meng
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China.,Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China
| | - Xiu-Ping Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Zhe Sun
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Hong-Qian Wang
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Wei-Feng Yu
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China. .,Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China.
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Koutsogiannaki S, Bu W, Hou L, Shibamura-Fujiogi M, Ishida H, Ohto U, Eckenhoff RG, Yuki K. The effect of anesthetics on toll like receptor 9. FASEB J 2020; 34:14645-14654. [PMID: 32901993 DOI: 10.1096/fj.202000791rr] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/17/2020] [Accepted: 08/20/2020] [Indexed: 12/11/2022]
Abstract
Toll like receptors (TLRs) are critical receptors to respond to danger signals, and their functions are relevant in the perioperative period. We previously reported that volatile anesthetics directly bound to TLR2 and TLR4 and attenuated their functions. Given that TLR9 can respond to mitochondrial DNA, a danger signal that is released upon tissue injury, we examined the role of anesthetics on TLR9 function. Our reporter assay showed that volatile anesthetics isoflurane and sevoflurane increased the activation of TLR9, while propofol attenuated it. TLR9 activation occurs via its dimerization. The dimerization is facilitated by unmethylated cytosine-phosphate-guanine (CpG) DNA as well as DNA containing cytosine at the second position from 5'-end (5'-xCx DNA). Our structural analysis using photoactivable anesthetics and rigid docking simulation showed that isoflurane and sevoflurane bound to both TLR9 dimer interface and 5'-xCx DNA binding site. Propofol bound to the TLR9 antagonist binding site. This is the first illustration that anesthetics can affect the binding of nucleic acids to their receptor. This study sets the foundation for the effect of anesthetics on TLR9 and will pave the way for future studies to determine the significance of such interactions in the clinical setting.
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Affiliation(s)
- Sophia Koutsogiannaki
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA, USA.,Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.,Department of Immunology, Harvard Medical School, Boston, MA, USA
| | - Weiming Bu
- Department of Anesthesia and Critical Care, University of Pennsylvania, Philadelphia, PA, USA
| | - Lifei Hou
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA, USA.,Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.,Department of Immunology, Harvard Medical School, Boston, MA, USA
| | - Miho Shibamura-Fujiogi
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA, USA.,Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.,Department of Immunology, Harvard Medical School, Boston, MA, USA
| | - Hanako Ishida
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Umeharu Ohto
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Roderic G Eckenhoff
- Department of Anesthesia and Critical Care, University of Pennsylvania, Philadelphia, PA, USA
| | - Koichi Yuki
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA, USA.,Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.,Department of Immunology, Harvard Medical School, Boston, MA, USA
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13
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Multiple sevoflurane exposures don't disturb the T-cell receptor repertoire in infant rhesus monkeys' thymus. Life Sci 2020; 248:117457. [PMID: 32092334 DOI: 10.1016/j.lfs.2020.117457] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 02/10/2020] [Accepted: 02/19/2020] [Indexed: 12/11/2022]
Abstract
AIMS Multiple surgical procedures and anesthesia increase the risk of the development in children. However, the influence of such exposures on the developing childhood immunity organs is rarely reported. MATERIALS AND METHODS High-throughput sequencing of T-cell receptor (TCR) repertoires (TCRseq) from rhesus monkeys' thymus was performed to investigate whether anesthetics could induce de novo antigen recognition via TCR or TCR development impairments. KEY FINDINGS No significant difference between sevoflurane and control groups regarding VJ gene combinations and diversity of V and J gene was seen, nor was there an obvious change in similar average number of Complementarity Determining Region 3 (CDR3) aa clonotypes. Our analysis of Rank abundance, Gini coefficient, Simpson index, Normalized Shannon Diversity Entropy (NSDE), Morisita-Horn Similarity Index (MHSI) and Bhattacharyya Distance (BD) indicated there is no difference in TCR diversity and similarity. SIGNIFICANCE These results suggest early events in thymic T cell development and repertoire generation are not abnormality after multiple sevoflurane exposure during childhood. The stabilization of the immune repertoires suggested the safety of sevoflurane in host immune response in children.
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14
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Mitsui Y, Koutsogiannaki S, Fujiogi M, Yuki K. In Vitro Model of Stretch-Induced Lung Injury to Study Different Lung Ventilation Regimens and the Role of Sedatives. TRANSLATIONAL PERIOPERATIVE AND PAIN MEDICINE 2020; 7:258-264. [PMID: 32542183 PMCID: PMC7295159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Currently lung injury is managed conservatively through supportive care including mechanical ventilation. However, mechanical ventilation can also cause additional lung injury due to over-stretch along with atelectasis and cytokine release. Here we developed an in vitro mechanical ventilation model using cyclic stretch of lung epithelial cells to mimic high and low tidal volume (TV) ventilation strategy, so that we could use this platform for pathophysiology analysis and screening for therapeutic drugs. METHOD We subjected MLE-15 cells to the following treatments. 1) No treatment, 2) lipopolysaccharide (100 ng/mL) stimulation for 24 hours, 3) mechanical stretch initiated at 6-hour time point for 18 hours, 4) LPS stimulation at time point 0 hour, and mechanical stretch was added at 6-hour time point for 18 hours. Biaxial cyclic stretch with a triangular wave was given via the Flexcell FX-6000 tension system to mimic low and high TV. Anesthetics dexmedetomidine and propofol were also tested. RESULT Our high TV mimic stretch increased cell death, while low TV mimic stretch did not affect the degree of cell death. Using this system, we examined the effect of sedatives commonly used in intensive care units on cell death and found that dexmedetomidine attenuated necrosis associated with stretch. CONCLUSION We described the in vitro cyclic stretch system mimicking high and low TV ventilation. High TV mimetic was associated with increased cell death. Dexmedetomidine attenuated the degree of cell death.
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Affiliation(s)
- Yusuke Mitsui
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children’s Hospital, Boston, Massachusetts, 02115, USA,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, 02115, USA
| | - Sophia Koutsogiannaki
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children’s Hospital, Boston, Massachusetts, 02115, USA,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, 02115, USA
| | - Miho Fujiogi
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children’s Hospital, Boston, Massachusetts, 02115, USA,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, 02115, USA
| | - Koichi Yuki
- Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children’s Hospital, Boston, Massachusetts, 02115, USA,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, 02115, USA
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15
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Okuno T, Koutsogiannaki S, Hou L, Bu W, Ohto U, Eckenhoff RG, Yokomizo T, Yuki K. Volatile anesthetics isoflurane and sevoflurane directly target and attenuate Toll-like receptor 4 system. FASEB J 2019; 33:14528-14541. [PMID: 31675483 DOI: 10.1096/fj.201901570r] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
General anesthesia has been the requisite component of surgical procedures for over 150 yr. Although immunomodulatory effects of volatile anesthetics have been growingly appreciated, the molecular mechanism has not been understood. In septic mice, the commonly used volatile anesthetic isoflurane attenuated the production of 5-lipoxygenase products and IL-10 and reduced CD11b and intercellular adhesion molecule-1 expression on neutrophils, suggesting the attenuation of TLR4 signaling. We confirmed the attenuation of TLR4 signaling in vitro and their direct binding to TLR4-myeloid differentiation-2 (MD-2) complex by photolabeling experiments. The binding sites of volatile anesthetics isoflurane and sevoflurane were located near critical residues for TLR4-MD-2 complex formation and TLR4-MD-2-LPS dimerization. Additionally, TLR4 activation was not attenuated by intravenous anesthetics, except for a high concentration of propofol. Considering the important role of TLR4 system in the perioperative settings, these findings suggest the possibility that anesthetic choice may modulate the outcome in patients or surgical cases in which TLR4 activation is expected.-Okuno, T., Koutsogiannaki, S., Hou, L., Bu, W., Ohto, U., Eckenhoff, R. G., Yokomizo, T., Yuki, K. Volatile anesthetics isoflurane and sevoflurane directly target and attenuate Toll-like receptor 4 system.
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Affiliation(s)
- Toshiaki Okuno
- Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan
| | - Sophia Koutsogiannaki
- Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA
| | - Lifei Hou
- Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA
| | - Weiming Bu
- Department of Anesthesia and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Umeharu Ohto
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Roderic G Eckenhoff
- Department of Anesthesia and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Takehiko Yokomizo
- Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan
| | - Koichi Yuki
- Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA
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16
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Koutsogiannaki S, Hou L, Babazada H, Okuno T, Blazon-Brown N, Soriano SG, Yokomizo T, Yuki K. The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain-Fas-associated death domain interaction. FASEB J 2019; 33:12668-12679. [PMID: 31513427 DOI: 10.1096/fj.201901360r] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Sepsis remains a significant health care burden, with high morbidities and mortalities. Patients with sepsis often require general anesthesia for procedures and imaging studies. Knowing that anesthetic drugs can pose immunomodulatory effects, it would be critical to understand the impact of anesthetics on sepsis pathophysiology. The volatile anesthetic sevoflurane is a common general anesthetic derived from ether as a prototype. Using a murine sepsis model induced by cecal ligation and puncture surgery, we examined the impact of sevoflurane on sepsis outcome. Different from volatile anesthetic isoflurane, sevoflurane exposure significantly improved the outcome of septic mice. This was associated with less apoptosis in the spleen. Because splenic apoptosis was largely attributed to the apoptosis of neutrophils, we examined the effect of sevoflurane on FasL-induced neutrophil apoptosis. Sevoflurane exposure significantly attenuated apoptosis. Sevoflurane did not affect the binding of FasL to the extracellular domain of Fas receptor. Instead, in silico analysis suggested that sevoflurane would bind to the interphase between Fas death domain (DD) and Fas-associated DD (FADD). The effect of sevoflurane on Fas DD-FADD interaction was examined using fluorescence resonance energy transfer (FRET). Sevoflurane attenuated FRET efficiency, indicating that sevoflurane hindered the interaction between Fas DD and FADD. The predicted sevoflurane binding site is known to play a significant role in Fas DD-FADD interaction, supporting our in vitro and in vivo apoptosis results.-Koutsogiannaki, S., Hou, L., Babazada, H., Okuno, T., Blazon-Brown, N., Soriano, S. G., Yokomizo, T., Yuki, K. The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain-Fas-associated death domain interaction.
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Affiliation(s)
- Sophia Koutsogiannaki
- Cardiac Anesthesia Division, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA
| | - Lifei Hou
- Cardiac Anesthesia Division, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA
| | - Hasan Babazada
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Toshiaki Okuno
- Department of Biochemistry, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Nathan Blazon-Brown
- Cardiac Anesthesia Division, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Sulpicio G Soriano
- Cardiac Anesthesia Division, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA
| | - Takehiko Yokomizo
- Department of Biochemistry, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Koichi Yuki
- Cardiac Anesthesia Division, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.,Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA
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17
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Nieuwenhuijs-Moeke GJ, Nieuwenhuijs VB, Seelen MAJ, Berger SP, van den Heuvel MC, Burgerhof JGM, Ottens PJ, Ploeg RJ, Leuvenink HGD, Struys MMRF. Propofol-based anaesthesia versus sevoflurane-based anaesthesia for living donor kidney transplantation: results of the VAPOR-1 randomized controlled trial. Br J Anaesth 2018; 118:720-732. [PMID: 28510740 DOI: 10.1093/bja/aex057] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/13/2017] [Indexed: 12/22/2022] Open
Abstract
Background Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia-reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia-reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation. Methods Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr. Results Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N -acetyl-β- d -glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO [952.8 (interquartile range 311.8-1893.0) pg mmol -1 ] compared with PROP [301.2 (202.0-504.7) pg mmol -1 ]. This was the same for NAG: SEVO, 1.835 (1.162-2.457) IU mmol -1 vs PROP, 1.078 (0.819-1.713) IU mmol -1 . Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate ( P =0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P =0.020). The difference between PROP and SEVO (11%) was not significant ( P =0.110). Conclusions The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome. Clinical trial registration NCT01248871.
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Affiliation(s)
| | - V B Nieuwenhuijs
- Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.,Department of Surgery, Isala, Zwolle, The Netherlands
| | | | | | | | - J G M Burgerhof
- Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - P J Ottens
- Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - R J Ploeg
- Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.,Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - H G D Leuvenink
- Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - M M R F Struys
- Department of Anaesthesiology.,Department of Anaesthesia, Ghent University, Ghent, Belgium
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18
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Perry NJS, Wigmore T. Propofol (TIVA) Versus Volatile-Based Anesthetics: Is There Any Oncological Benefit? CURRENT ANESTHESIOLOGY REPORTS 2018. [DOI: 10.1007/s40140-018-0296-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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19
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Shah S, Hariharan U, Bhargava A. Recent trends in anaesthesia and analgesia for breast cancer surgery. TRENDS IN ANAESTHESIA AND CRITICAL CARE 2018. [DOI: 10.1016/j.tacc.2018.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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20
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Zheng X, Wang Y, Dong L, Zhao S, Wang L, Chen H, Xu Y, Wang G. Effects of propofol-based total intravenous anesthesia on gastric cancer: a retrospective study. Onco Targets Ther 2018. [PMID: 29535538 PMCID: PMC5840299 DOI: 10.2147/ott.s156792] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Several kinds of cancer surgeries with propofol-based total intravenous anesthesia (TIVA) have been shown to have better outcomes than those with sevoflurane-based inhalational anesthesia (INHA). However, the effects of this anesthetic technique have not been investigated in patients with gastric cancer. In this study, the authors retrospectively examined the link between the choice of anesthetic technique and overall survival in patients undergoing gastric cancer resection. Methods We conducted a retrospective analysis of the database of all patients undergoing gastric cancer resection for gastric cancer between 2007 and 2012. Patients who received TIVA or INHA were administered patient-controlled intravenous analgesia for 72-120 hours postoperatively. Survival was estimated using the Kaplan-Meier log-rank test, and associations between anesthetic technique and outcomes were analyzed using Cox proportional hazards regressions after propensity matching. Results A total of 2,856 anesthetics using INHA or TIVA were delivered in the study period. After propensity matching, 897 patients remained in each group. According to Kaplan-Meier analysis, the use of TIVA was associated with improved survival (P<0.001). TIVA was associated with a hazard ratio (HR) of 0.67 (95% confidence interval [CI]: 0.58-0.77) for death in univariate analysis and 0.65 (95% CI: 0.56-0.75) after a multivariate analysis of known confounders in the matched group. Cancer stage (HR =0.74, 95% CI: 0.64-0.86, P<0.001) and degree of differentiation (HR =1.28, 95% CI: 1.11-1.47, P<0.001) were also associated with survival in the univariate analysis in the matched group. In the multivariable Cox model, cancer stage (HR =0.72, 95% CI: 0.62-0.84, P<0.001) and degree of differentiation (HR =1.23, 95% CI: 1.07-1.42, P<0.001) were associated with survival in the matched group. Conclusion These results indicate that TIVA may be associated with improved survival in gastric cancer patients who undergo resection.
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Affiliation(s)
- Xiaoyu Zheng
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yu Wang
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Linlin Dong
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Su Zhao
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Liping Wang
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Hong Chen
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yang Xu
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Guonian Wang
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
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21
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Koutsogiannaki S, Schaefers MM, Okuno T, Ohba M, Yokomizo T, Priebe GP, DiNardo JA, Sulpicio SG, Yuki K. From the Cover: Prolonged Exposure to Volatile Anesthetic Isoflurane Worsens the Outcome of Polymicrobial Abdominal Sepsis. Toxicol Sci 2018; 156:402-411. [PMID: 28003439 DOI: 10.1093/toxsci/kfw261] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Sepsis continues to result in high morbidity and mortality. General anesthesia is often administered to septic patients, but the impacts of general anesthesia on host defense are not well understood. General anesthesia can be given by volatile and intravenous anesthetics. Our previous in vitro study showed that volatile anesthetic isoflurane directly inhibits leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), critical adhesion molecules on leukocytes. Thus, the role of isoflurane exposure on in vivo LFA-1 and Mac-1 function was examined using polymicrobial abdominal sepsis model in mice. As a comparison, intravenous anesthetic propofol was given to a group of mice. Wild type, LFA-1, Mac-1, and adhesion molecule-1 knockout mice were used. Following the induction of polymicrobial abdominal sepsis by cecal ligation and puncture, groups of mice were exposed to isoflurane for either 2 or 6 h, or to propofol for 6 h, and their outcomes were examined. Bacterial loads in tissues and blood, neutrophil recruitment to the peritoneal cavity and phagocytosis were studied. Six hours of isoflurane exposure worsened the outcome of abdominal sepsis (P < .0001) with higher bacterial loads in tissues, but 2 h of isoflurane or 6 h of propofol exposure did not. Isoflurane impaired neutrophil recruitment to the abdominal cavity by inhibiting LFA-1 function. Isoflurane also impaired bacterial phagocytosis via complement receptors including Mac-1. In conclusion, prolonged isoflurane exposure worsened the outcome of experimental polymicrobial abdominal sepsis and was associated with impaired neutrophil recruitment and bacterial phagocytosis via reduced LFA-1 and Mac-1 function.
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Affiliation(s)
- Sophia Koutsogiannaki
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115
| | - Matthew M Schaefers
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115
| | - Toshiaki Okuno
- Department of Biochemistry, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Mai Ohba
- Department of Biochemistry, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Takehiko Yokomizo
- Department of Biochemistry, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Gregory P Priebe
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115
| | - James A DiNardo
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115
| | - Soriano G Sulpicio
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115
| | - Koichi Yuki
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115
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22
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Gudaitytė J, Dvylys D, Šimeliūnaitė I. Anaesthetic challenges in cancer patients: current therapies and pain management. Acta Med Litu 2017; 24:121-127. [PMID: 28845130 PMCID: PMC5566951 DOI: 10.6001/actamedica.v24i2.3493] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
THE OBJECTIVE The aim is to present the major effects of cancer treatment (chemotherapy, radiotherapy, surgery) that the anaesthesiologist should consider preoperatively, and to review techniques of the analgesic management of the disease. MATERIALS AND METHODS To summarize the major challenges that cancer patients present for the anaesthesiologists, a literature review was conducted. Articles presenting evidence or reviewing the possible effects of anaesthetics on cancer cells were also included. Online databases of Science Direct, PubMed, and ELSEVIER, as well as reference lists of included studies were searched. Articles published from 2005 to 2016 were selected. RESULTS Anaesthesiologists should pay attention to patients receiving chemotherapy and its side effects on organ systems. Bleomycin causes pulmonary damage, anthracyclines are cardiotoxic, and platinum-based chemotherapy agents are nephrotoxic. A lot of chemotherapy agents lead to abnormal liver function, vomiting, diarrhoea, etc. Surgery itself is suspected to be associated with an increased risk of metastasis and recurrence of cancer. Regional anaesthesia and general anaesthesia with propofol should be used and volatile agents should be avoided to prevent cancer patients from perioperative immunosuppression that leads to increased risk of cancer recurrence. Pain management for palliative patients remains a major problem. CONCLUSIONS To provide the best treatment for cancer patients, cooperation of anaesthesiologists with oncologists and surgeons becomes imperative. It has been established that anaesthetic techniques and drugs could minimize the perioperative inflammation. However, further research of the perioperative "onco-anaesthetic" is needed.
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Affiliation(s)
- Jūratė Gudaitytė
- Department of Anaesthesiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Dominykas Dvylys
- Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Indrė Šimeliūnaitė
- Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
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23
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Yuki K, Eckenhoff RG. Mechanisms of the Immunological Effects of Volatile Anesthetics: A Review. Anesth Analg 2017; 123:326-35. [PMID: 27308954 DOI: 10.1213/ane.0000000000001403] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Volatile anesthetics (VAs) have been in clinical use for a very long time. Their mechanism of action is yet to be fully delineated, but multiple ion channels have been reported as targets for VAs (canonical VA targets). It is increasingly recognized that VAs also manifest effects outside the central nervous system, including on immune cells. However, the literature related to how VAs affect the behavior of immune cells is very limited, but it is of interest that some canonical VA targets are reportedly expressed in immune cells. Here, we review the current literature and describe canonical VA targets expressed in leukocytes and their known roles. In addition, we introduce adhesion molecules called β2 integrins as noncanonical VA targets in leukocytes. Finally, we propose a model for how VAs affect the function of neutrophils, macrophages, and natural killer cells via concerted effects on multiple targets as examples.
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Affiliation(s)
- Koichi Yuki
- From the *Department of Anesthesiology, Perioperative and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, Massachusetts; †Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; and ‡Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Abstract
Volatile general anesthetics continue to be an important part of clinical anesthesia worldwide. The impact of volatile anesthetics on the immune system has been investigated at both mechanistic and clinical levels, but previous studies have returned conflicting findings due to varied protocols, experimental environments, and subject species. While many of these studies have focused on the immunosuppressive effects of volatile anesthetics, compelling evidence also exists for immunoactivation. Depending on the clinical conditions, immunosuppression and activation due to volatile anesthetics can be either detrimental or beneficial. This review provides a balanced perspective on the anesthetic modulation of innate and adaptive immune responses as well as indirect effectors of immunity. Potential mechanisms of immunomodulation by volatile anesthetics are also discussed. A clearer understanding of these issues will pave the way for clinical guidelines that better account for the impact of volatile anesthetics on the immune system, with the ultimate goal of improving perioperative management.
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25
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Lin CC, Chen DY, Tang KT, Chao YH, Shen CH, Lui PW. Inhibitory effects of propofol on Th17 cell differentiation. Immunopharmacol Immunotoxicol 2017; 39:211-218. [PMID: 28555509 DOI: 10.1080/08923973.2017.1327962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous anesthetic agent in daily practice. It has been reported to show immunomodulatory activity. However, the effect of propofol on the differention of T cells remains unclear. In this study, we demonstrated for the first time that propofol inhibited both interleukin (IL)-6 plus transforming growth factor-β (TGF-β)-induced Th17 cell differentiation in vitro and in LPS-challenged mice. Propofol also suppressed the IL-6-induced phosphorylation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription (STAT3) pathway, a cytokine-activated essential transcription factor in Th17 cell development, which occurred concomitantly with the enhancement of suppressor of cytokine signaling-3 (SOCS3) expression involved in the downregulation of STAT3 phosphorylation. These data extend our knowledge of the immunosuppressive effects of propofol and their underlying mechanism.
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Affiliation(s)
- Chi-Chien Lin
- a Institute of Biomedical Science, National Chung Hsing University , Taichung , Taiwan.,b Department of Medical Research , China Medical University Hospital , Taichung , Taiwan.,c Department of Biotechnology , Asia University , Taichung , Taiwan
| | - Der-Yuan Chen
- d Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine , Taichung Veterans General Hospital , Taichung , Taiwan.,e School of Medicine , National Yang-Ming University , Taipei , Taiwan.,f Department of Medical Research , Taichung Veterans General Hospital , Taichung , Taiwan
| | - Kuo-Tung Tang
- a Institute of Biomedical Science, National Chung Hsing University , Taichung , Taiwan.,d Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine , Taichung Veterans General Hospital , Taichung , Taiwan
| | - Ya-Hsuan Chao
- a Institute of Biomedical Science, National Chung Hsing University , Taichung , Taiwan
| | - Ching-Hui Shen
- e School of Medicine , National Yang-Ming University , Taipei , Taiwan.,g Department of Anesthesiology , Taichung Veterans General Hospital , Taichung , Taiwan
| | - Ping-Wing Lui
- a Institute of Biomedical Science, National Chung Hsing University , Taichung , Taiwan.,e School of Medicine , National Yang-Ming University , Taipei , Taiwan.,f Department of Medical Research , Taichung Veterans General Hospital , Taichung , Taiwan.,g Department of Anesthesiology , Taichung Veterans General Hospital , Taichung , Taiwan
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The effect of different anesthetics on tumor cytotoxicity by natural killer cells. Toxicol Lett 2016; 266:23-31. [PMID: 27940100 DOI: 10.1016/j.toxlet.2016.12.007] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 12/05/2016] [Accepted: 12/08/2016] [Indexed: 02/06/2023]
Abstract
A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anesthetics-based general anesthesia. However, the underlying mechanism is yet to be determined. Because natural killer (NK) cells are implicated as important immune cells for tumor recurrence/metastasis in the perioperative period, we examined the effect of different anesthetics on NK cell-mediated tumor cytotoxicity. Because adhesion molecule leukocyte function-associated antigen-1 (LFA-1) is functionally important in NK cells and is inhibited by commonly used volatile anesthetics isoflurane and sevoflurane, we hypothesized that these anesthetics would attenuate NK cell-mediated cytotoxicity. Using human NK cell line NK92-MI cells and tumor cell line K562 cells as a model system, we performed cytotoxicity, proliferation, conjugation and degranulation assays. Lytic granule polarization was also assessed. We showed that isoflurane, sevoflurane and LFA-1 inhibitor BIRT377 attenuated cytotoxicity, and reduced conjugation and polarization, but not degranulation of NK cells. Our data suggest that isoflurane and sevoflurane attenuated NK cell-mediated cytotoxicity at least partly by their LFA-1 inhibition in vitro. Whether or not isoflurane and sevoflurane attenuate NK cell-mediated tumor cytotoxicity in patients needs to be determined in the future.
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Adenosine Receptor Adora2b Plays a Mechanistic Role in the Protective Effect of the Volatile Anesthetic Sevoflurane during Liver Ischemia/Reperfusion. Anesthesiology 2016; 125:547-60. [DOI: 10.1097/aln.0000000000001234] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Abstract
Background
Liver ischemia/reperfusion (IR) injury is characterized by hepatic tissue damage and an inflammatory response. This is accompanied by the formation and vascular sequestration of platelet–neutrophil conjugates (PNCs). Signaling through Adora2b adenosine receptors can provide liver protection. Volatile anesthetics may interact with adenosine receptors. This study investigates potential antiinflammatory effects of the volatile anesthetic sevoflurane during liver IR.
Methods
Experiments were performed ex vivo with human blood and in a liver IR model with wild-type, Adora2a−/−, and Adora2b−/− mice. The effect of sevoflurane on platelet activation, PNC formation and sequestration, cytokine release, and liver damage (alanine aminotransferase release) was analyzed using flow cytometry, luminometry, and immunofluorescence. Adenosine receptor expression in liver tissue was analyzed using immunohistochemistry and real-time polymerase chain reaction.
Results
Ex vivo experiments indicate that sevoflurane inhibits platelet and leukocyte activation (n = 5). During liver IR, sevoflurane (2 Vol%) decreased PNC formation 2.4-fold in wild-type (P < 0.05) but not in Adora2b−/− mice (n ≥ 5). Sevoflurane reduced PNC sequestration 1.9-fold (P < 0.05) and alanine aminotransferase release 3.5-fold (P < 0.05) in wild-type but not in Adora2b−/− mice (n = 5). In Adora2a−/− mice, sevoflurane also inhibited PNC formation and cytokine release. Sevoflurane diminished cytokine release (n ≥ 3) and increased Adora2b transcription and expression in liver tissue of wild-types (n = 4).
Conclusions
Our experiments highlight antiinflammatory and tissue-protective properties of sevoflurane during liver IR and reveal a mechanistic role of Adora2b in sevoflurane-associated effects. The targeted use of sevoflurane not only as an anesthetic but also to prevent IR damage is a promising approach in the treatment of critically ill patients.
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Inhaled Anesthetics Exert Different Protective Properties in a Mouse Model of Ventilator-Induced Lung Injury. Anesth Analg 2016; 123:143-51. [DOI: 10.1213/ane.0000000000001296] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Effects of Volatile Anesthetics on Mortality and Postoperative Pulmonary and Other Complications in Patients Undergoing Surgery. Anesthesiology 2016; 124:1230-45. [DOI: 10.1097/aln.0000000000001120] [Citation(s) in RCA: 123] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Abstract
Background
It is not known whether modern volatile anesthetics are associated with less mortality and postoperative pulmonary or other complications in patients undergoing general anesthesia for surgery.
Methods
A systematic literature review was conducted for randomized controlled trials fulfilling following criteria: (1) population: adult patients undergoing general anesthesia for surgery; (2) intervention: patients receiving sevoflurane, desflurane, or isoflurane; (3) comparison: volatile anesthetics versus total IV anesthesia or volatile anesthetics; (4) reporting on: (a) mortality (primary outcome) and (b) postoperative pulmonary or other complications; (5) study design: randomized controlled trials. The authors pooled treatment effects following Peto odds ratio (OR) meta-analysis and network meta-analysis methods.
Results
Sixty-eight randomized controlled trials with 7,104 patients were retained for analysis. In cardiac surgery, volatile anesthetics were associated with reduced mortality (OR = 0.55; 95% CI, 0.35 to 0.85; P = 0.007), less pulmonary (OR = 0.71; 95% CI, 0.52 to 0.98; P = 0.038), and other complications (OR = 0.74; 95% CI, 0.58 to 0.95; P = 0.020). In noncardiac surgery, volatile anesthetics were not associated with reduced mortality (OR = 1.31; 95% CI, 0.83 to 2.05, P = 0.242) or lower incidences of pulmonary (OR = 0.67; 95% CI, 0.42 to 1.05; P = 0.081) and other complications (OR = 0.70; 95% CI, 0.46 to 1.05; P = 0.092).
Conclusions
In cardiac, but not in noncardiac, surgery, when compared to total IV anesthesia, general anesthesia with volatile anesthetics was associated with major benefits in outcome, including reduced mortality, as well as lower incidence of pulmonary and other complications. Further studies are warranted to address the impact of volatile anesthetics on outcome in noncardiac surgery.
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Abstract
Exposure to anesthesia and surgery has been hypothesized to increase the risk of developing Alzheimer's disease (AD). While the exact pathogenesis of AD remains unknown, it potentially involves specific proteins (eg, amyloid beta and tau) and neuroinflammation. A growing body of preclinical evidence also suggests that anesthetic agents interact with the components that mediate AD neuropathology at multiple levels. However, it remains unclear whether anesthesia and surgery are associated with an increased risk of AD in humans. To date, there have not been randomized controlled trials to provide evidence for such a causal relationship. Besides, observational studies showed inconsistent results. A meta-analysis of 15 case-control studies revealed no statistically significant association between general anesthesia and the development of AD (pooled odds ratio [OR] =1.05; P=0.43). However, a few retrospective cohort studies have demonstrated that exposure to anesthesia and surgery is associated with an increased risk of AD. Thus, well-designed studies with longer follow-up periods are still needed to define the role of anesthesia in relation to the development of AD.
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Affiliation(s)
- Chih-Wen Yang
- Department of Neurology, National Yang-Ming University Hospital, Ilan, Taipei, Taiwan, Republic of China ; National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
| | - Jong-Ling Fuh
- National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China ; Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
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Jung S, Yuki K. Differential effects of volatile anesthetics on leukocyte integrin macrophage-1 antigen. J Immunotoxicol 2015; 13:148-56. [PMID: 25746395 DOI: 10.3109/1547691x.2015.1019596] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Macrophage-1 antigen (Mac-1, αMβ2) is a leukocyte adhesion molecule that plays a significant role in leukocyte crawling and phagocytosis, and is homologous to its sister protein leukocyte function-associated antigen-1 (LFA-1, αLβ2). The authors have previously demonstrated that volatile anesthetics isoflurane and sevoflurane bound to and inhibited LFA-1. Here, the hypothesis tested was that isoflurane and sevoflurane would inhibit Mac-1. A binding assay of Mac-1 to its ligand inter-cellular adhesion molecule-1 (ICAM-1) using V-bottom plates was established. The effect of isoflurane and sevoflurane on Mac-1 was examined using this ICAM-1 binding assay and by probing exposure of activation-sensitive epitopes. The docking program Glide was used to predict anesthetic binding site(s) on Mac-1. The functional role of this predicted binding site was then assessed by introducing point mutations in this region. Lastly, the effect of anesthetic on activating mutants was evaluated. The results indicated that isoflurane inhibited binding of Mac-1 to ICAM-1, but sevoflurane did not. Isoflurane also attenuated the exposure of the activation-sensitive epitopes. The docking simulation predicted the isoflurane binding site to be at the cavity underneath the α7 helix of the ligand binding domain (the αM I domain). Point mutants at this predicted binding site contained both activating and deactivating mutants, suggesting its functional significance. The binding of activating mutants αM-Y267A β2-WT and αM-L312A β2-WT to ICAM-1 was not affected by isoflurane, but binding of another activating mutant αM-WT β2-L132A was inhibited supporting the binding of isoflurane to this cavity. The conclusion reached from these findings was that isoflurane inhibited Mac-1 binding to ICAM-1 by binding to the cavity underneath the α7 helix of the αM I domain, but sevoflurane did not. Thus, because these common clinical volatile anesthetics demonstrated different effects on Mac-1, this implied their effects on the immune system might differ.
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Affiliation(s)
- Sungeun Jung
- a Department of Anesthesiology , Perioperative and Pain Medicine, Boston Children's Hospital , Boston , MA , USA and.,b Department of Anaesthesia , Harvard Medical School , Boston , MA , USA
| | - Koichi Yuki
- a Department of Anesthesiology , Perioperative and Pain Medicine, Boston Children's Hospital , Boston , MA , USA and.,b Department of Anaesthesia , Harvard Medical School , Boston , MA , USA
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Minguet G, Franck T, Joris J, Ceusters J, Mouithys-Mickalad A, Serteyn D, Sandersen C. Effects of isoflurane and sevoflurane on the neutrophil myeloperoxidase system of horses. Vet Immunol Immunopathol 2015; 165:93-7. [PMID: 25796094 DOI: 10.1016/j.vetimm.2015.02.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Revised: 02/10/2015] [Accepted: 02/26/2015] [Indexed: 02/01/2023]
Abstract
Volatile anaesthestics have shown to modulate the oxidative response of polymorphonuclear neutrophils (PMNs). We investigated the effects of isoflurane and sevoflurane on the degranulation of total and active myeloperoxidase (MPO) from horse PMNs and their direct interaction with MPO activity. Whole blood from horse was incubated in 1 and 2 minimal alveolar concentrations (MAC) of isoflurane or sevoflurane for 1h and PMNs were stimulated with cytochalasin B (CB) plus N-formyl-méthionyl-leucyl-phenylalanine (fMLP). After stimulation, the plasma was collected to measure total and active MPO by enzyme-linked immunosorbent assay (ELISA) and specific immunological extraction followed by enzymatic detection (SIEFED) respectively. The effects of 1 and 2 MAC of isoflurane and sevoflurane on the peroxidase and chlorination activity of pure MPO were assessed by fluorescence using Amplex red and 3'-(p-aminophenyl) fluorescein (APF) respectively and in parallel with a SIEFED assay to estimate the potential interaction of the anaesthetics with the enzyme. Although isoflurane and sevoflurane had inconsistent effects on total MPO release, both volatile agents reduced active MPO release and showed a direct inhibition on the peroxidase and the chlorination activity of the enzyme. A persistent interaction between MPO and anaesthetics was evidenced with isoflurane but not with sevoflurane.
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Affiliation(s)
- Grégory Minguet
- Department of Anaesthesia and Intensive Care Medicine, CHU de Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium.
| | - Thierry Franck
- Center for Oxygen Research and Development, Institute of Chemistry B6a, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium
| | - Jean Joris
- Department of Anaesthesia and Intensive Care Medicine, CHU de Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium
| | - Justine Ceusters
- Center for Oxygen Research and Development, Institute of Chemistry B6a, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium
| | - Ange Mouithys-Mickalad
- Center for Oxygen Research and Development, Institute of Chemistry B6a, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium
| | - Didier Serteyn
- Center for Oxygen Research and Development, Institute of Chemistry B6a, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium; Department of Clinical Sciences, Anaesthesiology and Equine Surgery, Faculty of Veterinary Medicine, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium
| | - Charlotte Sandersen
- Department of Clinical Sciences, Anaesthesiology and Equine Surgery, Faculty of Veterinary Medicine, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium
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Yuki K, Murakami N. Sepsis pathophysiology and anesthetic consideration. Cardiovasc Hematol Disord Drug Targets 2015; 15:57-69. [PMID: 25567335 PMCID: PMC4704087 DOI: 10.2174/1871529x15666150108114810] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 09/22/2014] [Accepted: 10/11/2014] [Indexed: 12/28/2022]
Abstract
Sepsis remains to be a significant health care issue associated with high mortality and healthcare cost, despite the extensive effort to better understand the pathophysiology of the sepsis. Recently updated clinical guideline for severe sepsis and septic shock, "Surviving Sepsis Campaign 2012", emphasizes the importance of early goal-directed therapy, which can be implemented in intraoperative management of sepsis patients. Herein, we review the updates of current guideline and discuss its application to anesthesic management. Furthermore, we review the recent advance in knowledge of sepsis pathophysiology, focusing on immune modulation, which may lead to new clinical therapeutic approach to sepsis.
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Affiliation(s)
- Koichi Yuki
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA
| | - Naoka Murakami
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA
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Bechtel A, Huffmyer J. Anesthetic Management for Cardiopulmonary Bypass. Semin Cardiothorac Vasc Anesth 2014; 18:101-16. [DOI: 10.1177/1089253214529607] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Cardiopulmonary bypass has revolutionized the practice of cardiac surgery and allows safe conduct of increasingly complex cardiac surgery. A brief review of the bypass circuit is undertaken in this review. A more thorough review of the anesthetic management is accomplished including choice of anesthetic medications and their effects. The inflammatory response to cardiopulmonary bypass is reviewed along with interventions that may help ameliorate the inflammation.
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Khanna AK, Perez ER, Laudanski K, Moraska A, III KCC. Perioperative care and cancer recurrence: Is there a connection? World J Anesthesiol 2014; 3:31-45. [DOI: 10.5313/wja.v3.i1.31] [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: 10/21/2013] [Revised: 12/13/2013] [Accepted: 02/18/2014] [Indexed: 02/06/2023] Open
Abstract
Cancer is the second most common cause of death in the United States. Metastatic disease is a more important cause of cancer-related death relative to primary tumor progression. Surgical excision is the primary treatment for most malignant tumors. However, surgery itself can inhibit important host defenses and promote the development of metastases. An altered balance between the metastatic potential of the tumor and the anti-metastatic host defenses, including cell-mediated immunity and natural killer cell function, is a plausible mechanism of increased cancer metastasis. This article reviews the increasingly recognized concept of anesthetic technique along with perioperative factors and their potential to affect long-term outcome after cancer surgery. The potential effect of intravenous anesthetics, volatile agents, local anesthetic drugs, opiates, and non-steroidal anti-inflammatory drugs are reviewed along with recent literature and ongoing clinical trials in this area. Regional anesthesia is increasingly emerging as a safer option with less cancer recurrence potential as compared to general anesthesia. Blood transfusion, pain, stress, use of beta-blockers, and hypothermia are other potentially important perioperative factors to consider.
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Landoni G, Greco T, Biondi-Zoccai G, Nigro Neto C, Febres D, Pintaudi M, Pasin L, Cabrini L, Finco G, Zangrillo A. Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery. Br J Anaesth 2013; 111:886-896. [PMID: 23852263 DOI: 10.1093/bja/aet231] [Citation(s) in RCA: 126] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival. METHODS We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012). RESULTS We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004, number needed to treat 74, I(2)=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were individually associated with a reduction in mortality when compared with TIVA. CONCLUSIONS Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.
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Affiliation(s)
- G Landoni
- Anesthesia and Intensive Care Department, San Raffaele Scientific Institute, Milan, Italy
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Anesthesia, surgery, illness and Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2013; 47:162-6. [PMID: 22729032 PMCID: PMC3509241 DOI: 10.1016/j.pnpbp.2012.06.011] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Revised: 06/12/2012] [Accepted: 06/17/2012] [Indexed: 11/24/2022]
Abstract
Patients and their families have, for many decades, detected subtle changes in cognition subsequent to surgery, and only recently has this been subjected to scientific scrutiny. Through a combination of retrospective human studies, small prospective biomarker studies, and experiments in animals, it is now clear that durable consequences of both anesthesia and surgery occur, and that these intersect with the normal processes of aging, and the abnormal processes of chronic neurodegeneration. It is highly likely that inflammatory cascades are at the heart of this intersection, and if confirmed, this suggests a therapeutic strategy to mitigate enhanced neuropathology in vulnerable surgical patients.
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Weiser BP, Woll KA, Dailey WP, Eckenhoff RG. Mechanisms revealed through general anesthetic photolabeling. CURRENT ANESTHESIOLOGY REPORTS 2013; 4:57-66. [PMID: 24563623 DOI: 10.1007/s40140-013-0040-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
General anesthetic photolabels are used to reveal molecular targets and molecular binding sites of anesthetic ligands. After identification, the relevance of anesthetic substrates or binding sites can be tested in biological systems. Halothane and photoactive analogs of isoflurane, propofol, etomidate, neurosteroids, anthracene, and long chain alcohols have been used in anesthetic photolabeling experiments. Interrogated protein targets include the nicotinic acetylcholine receptor, GABAA receptor, tubulin, leukocyte function-associated antigen-1, and protein kinase C. In this review, we summarize insights revealed by photolabeling these targets, as well as general features of anesthetics, such as their propensity to partition to mitochondria and bind voltage-dependent anion channels. The theory of anesthetic photolabel design and the experimental application of photoactive ligands are also discussed.
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Affiliation(s)
- Brian P Weiser
- Department of Anesthesiology & Critical Care, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104 ; Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104
| | - Kellie A Woll
- Department of Anesthesiology & Critical Care, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104 ; Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104
| | - William P Dailey
- Department of Chemistry, University of Pennsylvania School of Arts and Sciences, 231 S. 34th Street, Philadelphia, PA 19104
| | - Roderic G Eckenhoff
- Department of Anesthesiology & Critical Care, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104
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Ash SA, Buggy DJ. Does regional anaesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence. Best Pract Res Clin Anaesthesiol 2013; 27:441-56. [PMID: 24267550 DOI: 10.1016/j.bpa.2013.10.005] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 10/07/2013] [Indexed: 12/12/2022]
Abstract
Cancer continues to be a key cause of morbidity and mortality worldwide and its overall incidence continues to increase. Anaesthetists are increasingly faced with the challenge of managing cancer patients, for surgical resection to debulk or excise the primary tumour, or for surgical emergencies in patients on chemotherapy or for the analgesic management of disease- or treatment-related chronic pain. Metastatic recurrence is a concern. Surgery and a number of perioperative factors are suspected to accelerate tumour growth and potentially increase the risk of metastatic recurrence. Retrospective analyses have suggested an association between anaesthetic technique and cancer outcomes, and anaesthetists have sought to ameliorate the consequences of surgical trauma and minimise the impact of anaesthetic interventions. Just how anaesthesia and analgesia impact cancer recurrence and consequent survival is very topical, as understanding the potential mechanisms and interactions has an impact on the anaesthetist's ability to contribute to the successful outcome of oncological interventions. The outcome of ongoing, prospective, randomized trials are awaited with interest.
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Affiliation(s)
- Simon A Ash
- Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
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Yuki K, Bu W, Xi J, Shimaoka M, Eckenhoff R. Propofol shares the binding site with isoflurane and sevoflurane on leukocyte function-associated antigen-1. Anesth Analg 2013; 117:803-811. [PMID: 23960033 DOI: 10.1213/ane.0b013e3182a00ae0] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND We previously demonstrated that propofol interacted with the leukocyte adhesion molecule leukocyte function-associated antigen-1 (LFA-1) and inhibited the production of interleukin-2 via LFA-1 in a dependent manner. However, the binding site(s) of propofol on LFA-1 remains unknown. METHODS First, the inhibition of LFA-1's ligand binding by propofol was confirmed in an enzyme-linked immunosorbent assay (ELISA) ELISA-type assay. The binding site of propofol on LFA-1 was probed with a photolabeling experiment using a photoactivatable propofol analog called azi-propofol-m. The adducted residues of LFA-1 by this compound were determined using liquid chromatography-mass spectrometry. In addition, the binding of propofol to the ligand-binding domain of LFA-1 was examined using 1-aminoanthracene (1-AMA) displacement assay. Furthermore, the binding site(s) of 1-AMA and propofol on LFA-1 was studied using the docking program GLIDE. RESULTS We demonstrated that propofol impaired the binding of LFA-1 to its ligand intercellular adhesion molecule-1. The photolabeling experiment demonstrated that the adducted residues were localized in the allosteric cavity of the ligand-binding domain of LFA-1 called "lovastatin site." The shift of fluorescence spectra was observed when 1-AMA was coincubated with the low-affinity conformer of LFA-1 ligand-binding domain (wild-type [WT] αL I domain), not with the high-affinity conformer, suggesting that 1-AMA bound only to WT αL I domain. In the 1-AMA displacement assay, propofol decreased 1-AMA fluorescence signal (at 520 nm), suggesting that propofol competed with 1-AMA and bound to the WT αL I domain. The docking simulation demonstrated that both 1-AMA and propofol bound to the lovastatin site, which agreed with the photolabeling experiment. CONCLUSIONS We demonstrated that propofol bound to the lovastatin site in LFA-1. Previously we showed that the volatile anesthetics isoflurane and sevoflurane bound to this site. Taken together, the lovastatin site is an example of the common binding sites for anesthetics currently used clinically.
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Affiliation(s)
- Koichi Yuki
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115.
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Yuki K, Bu W, Shimaoka M, Eckenhoff R. Volatile anesthetics, not intravenous anesthetic propofol bind to and attenuate the activation of platelet receptor integrin αIIbβ3. PLoS One 2013; 8:e60415. [PMID: 23573252 PMCID: PMC3616120 DOI: 10.1371/journal.pone.0060415] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Accepted: 02/27/2013] [Indexed: 12/03/2022] Open
Abstract
Background In clinical reports, the usage of isoflurane and sevoflurane was associated with more surgical field bleeding in endoscopic sinus surgeries as compared to propofol. The activation of platelet receptor αIIbβ3 is a crucial event for platelet aggregation and clot stability. Here we studied the effect of isoflurane, sevoflurane, and propofol on the activation of αIIbβ3. Methods The effect of anesthetics on the activation of αIIbβ3 was probed using the activation sensitive antibody PAC-1 in both cell-based (platelets and αIIbβ3 transfectants) and cell-free assays. The binding sites of isoflurane on αIIbβ3 were explored using photoactivatable isoflurane (azi-isoflurane). The functional implication of revealed isoflurane binding sites were studied using alanine-scanning mutagenesis. Results Isoflurane and sevoflurane diminished the binding of PAC-1 to wild-type αIIbβ3 transfectants, but not to the high-affinity mutant, β3-N305T. Both anesthetics also impaired PAC-1 binding in a cell-free assay. In contrast, propofol did not affect the activation of αIIbβ3. Residues adducted by azi-isoflurane were near the calcium binding site (an important regulatory site termed SyMBS) just outside of the ligand binding site. The mutagenesis experiments demonstrated that these adducted residues were important in regulating integrin activation. Conclusions Isoflurane and sevoflurane, but not propofol, impaired the activation of αIIbβ3. Azi-isoflurane binds to the regulatory site of integrin αIIbβ3, thereby suggesting that isoflurane blocks ligand binding of αIIbβ3 in not a competitive, but an allosteric manner.
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Affiliation(s)
- Koichi Yuki
- Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
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Heaney A, Buggy DJ. Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis? Br J Anaesth 2013; 109 Suppl 1:i17-i28. [PMID: 23242747 DOI: 10.1093/bja/aes421] [Citation(s) in RCA: 264] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Cancer is a leading cause of morbidity and mortality worldwide and the ratio of incidence is increasing. Mortality usually results from recurrence or metastases. Surgical removal of the primary tumour is the mainstay of treatment, but this is associated with inadvertent dispersal of neoplastic cells into the blood and lymphatic systems. The fate of the dispersed cells depends on the balance of perioperative factors promoting tumour survival and growth (including surgery per se, many anaesthetics per se, acute postoperative pain, and opioid analgesics) together with the perioperative immune status of the patient. Available evidence from experimental cell culture and live animal data on these factors are summarized, together with clinical evidence from retrospective studies. Taken together, current data are sufficient only to generate a hypothesis that an anaesthetic technique during primary cancer surgery could affect recurrence or metastases, but a causal link can only be proved by prospective, randomized, clinical trials. Many are ongoing, but definitive results might not emerge for a further 5 yr or longer. Meanwhile, there is no hard evidence to support altering anaesthetic technique in cancer patients, pending the outcome of the ongoing clinical trials.
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Affiliation(s)
- A Heaney
- Department of Anaesthesia, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland
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Polak PE, Dull RO, Kalinin S, Sharp AJ, Ripper R, Weinberg G, Schwartz DE, Rubinstein I, Feinstein DL. Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis. J Neuroinflammation 2012; 9:272. [PMID: 23253693 PMCID: PMC3544665 DOI: 10.1186/1742-2094-9-272] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 11/26/2012] [Indexed: 02/08/2023] Open
Abstract
Background Inhalational anesthetics have been shown to influence T cell functions both in vitro and in vivo, in many cases inducing T cell death, suggesting that exposure to these drugs could modify the course of an autoimmune disease. We tested the hypothesis that in mice immunized to develop experimental autoimmune encephalomyelitis (EAE), a well established model of multiple sclerosis (MS), treatment with the commonly used inhalational anesthetic sevoflurane would attenuate disease symptoms. Methods C57Bl6 female mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide residues 35 to 55 to induce a chronic demyelinating disease. At day 10 after immunization, the mice were subjected to 2 h of 2.5% sevoflurane in 100% oxygen, or 100% oxygen, alone. Following treatment, clinical scores were monitored up to 4 weeks, after which brain histology was performed to measure the effects on astrocyte activation and lymphocyte infiltration. Effects of sevoflurane on T cell activation were studied using splenic T cells isolated from MOG peptide-immunized mice, restimulated ex vivo with MOG peptide or with antibodies to CD3 and CD28, and in the presence of different concentrations of sevoflurane. T cell responses were assessed 1 day later by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for proliferation, lactate dehydrogenase (LDH) release for cell death, and inflammatory activation by production of interleukin (IL)-17 and interferon (IFN)γ. Results Clinical scores in the oxygen-treated group increased until day 28 at which time they showed moderate to severe disease (average clinical score of 2.9). In contrast, disease progression in the sevoflurane-treated group increased to 2.1 at day 25, after which it remained unchanged until the end of the study. Immunohistochemical analysis revealed reduced numbers of infiltrating leukocytes and CD4+ cells in the CNS of the sevoflurane-treated mice, as well as reduced glial cell activation. In splenic T cells, low doses of sevoflurane reduced IFNγ production, cell proliferation, and increased LDH release. Conclusions These results are the first to show attenuation of EAE disease by an inhaled anesthetic and are consistent with previous reports that inhaled anesthetics, including sevoflurane, can suppress T cell activation that, in the context of autoimmune diseases such as MS, could lead to reduced clinical progression.
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Affiliation(s)
- Paul E Polak
- Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA
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The volatile anesthetic sevoflurane inhibits activation of neutrophil granulocytes during simulated extracorporeal circulation. Int Immunopharmacol 2012; 14:202-8. [DOI: 10.1016/j.intimp.2012.07.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2012] [Revised: 07/10/2012] [Accepted: 07/11/2012] [Indexed: 11/19/2022]
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Yuki K, Bu W, Xi J, Sen M, Shimaoka M, Eckenhoff RG. Isoflurane binds and stabilizes a closed conformation of the leukocyte function-associated antigen-1. FASEB J 2012; 26:4408-17. [PMID: 22815384 DOI: 10.1096/fj.12-212746] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
We previously demonstrated that isoflurane targets lymphocyte function-associated antigen-1 (LFA-1), a critical adhesion molecule for leukocyte arrest. However, it remains to be determined how isoflurane interacts with the full ectodomain LFA-1 and modulates its conformation and function. Isoflurane binding sites on the full ectodomain LFA-1 were probed by photolabeling using photoactivatable isoflurane (azi-isoflurane). The adducted residues were determined by liquid chromatography/mass spectrometry analysis. Separately, docking simulations were performed to predict binding sites. Point mutations were introduced around isoflurane binding sites. The significance of isoflurane's effect was assessed in both intracellular adhesion molecule-1 (ICAM-1) binding assays and epitope mapping of activation-sensitive antibodies using flow cytometry. Two isoflurane binding sites were identified using photolabeling and were further validated by the docking simulation: one at the hydrophobic pocket in the ICAM-1 binding domain (the αI domain); the other at the βI domain. Mutagenesis of the α'1 helix showed that isoflurane binding sites at the βI domain were significantly important in modulating LFA-1 function and conformation. Epitope mapping using activation-sensitive antibodies suggested that isoflurane stabilized LFA-1 in the closed conformation. This study suggested that isoflurane binds to both the αI and βI domains allosteric to the ICAM-1 binding site, and that isoflurane binding stabilizes LFA-1 in the closed conformation.
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Affiliation(s)
- Koichi Yuki
- Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA.
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Cata JP, Gottumukkala V, Sessler DI. How regional analgesia might reduce postoperative cancer recurrence. ACTA ACUST UNITED AC 2012. [DOI: 10.1016/j.eujps.2011.08.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Recent advances in epidural analgesia. Anesthesiol Res Pract 2011; 2012:309219. [PMID: 22174708 PMCID: PMC3232404 DOI: 10.1155/2012/309219] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2011] [Accepted: 08/13/2011] [Indexed: 01/08/2023] Open
Abstract
Neuraxial anesthesia is a term that denotes all forms of central blocks, involving the spinal, epidural, and caudal spaces. Epidural anesthesia is a versatile technique widely used in anesthetic practice. Its potential to decrease postoperative morbidity and mortality has been demonstrated by numerous studies. To maximize its perioperative benefits while minimizing potential adverse outcomes, the knowledge of factors affecting successful block placement is essential. This paper will provide an overview of the pertinent anatomical, pharmacological, immunological, and technical aspects of epidural anesthesia in both adult and pediatric populations and will discuss the recent advances, the related rare but potentially devastating complications, and the current recommendations for the use of anticoagulants in the setting of neuraxial block placement.
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Current World Literature. Curr Opin Anaesthesiol 2011; 24:463-5. [DOI: 10.1097/aco.0b013e3283499d5a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
PURPOSE OF REVIEW To summarize key studies and recent thought on the role of neuroinflammation in chronic neurodegeneration, and whether it can be modulated by anesthesia and surgery. RECENT FINDINGS A large and growing body of evidence shows that neuroinflammation participates in the development of neurodegeneration associated with Alzheimer's disease. Modulation may be possible early in the pathogenesis, and less so when cognitive symptoms appear. A dysfunctional hypoinflammatory response may permit accelerated damage due to other mechanisms in late disease. The peripheral inflammatory response elicited by surgery itself appears to provoke a muted neuroinflammatory response, which enhances ongoing neurodegeneration in some models. Anesthetics have both anti-inflammatory and proinflammatory effects depending on the drug and concentration, but in general, appear to play a small role in neuroinflammation. Human studies at the intersection of chronic neurodegeneration, neuroinflammation, and surgery/anesthesia are rare. SUMMARY The perioperative period has the potential to modulate the progression of chronic neurodegenerative diseases. The growing number of elderly having surgery, combined with the expanding life expectancy, indicates the potential for this interaction to have considerable public health implications, and call for further research, especially in humans.
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Affiliation(s)
- Junxia X Tang
- Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
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