Zusammenfassung
Hintergrund
Akut auftretende Organschädigungen tragen im perioperativen Kontext signifikant zu Morbidität und Mortalität bei.
Ziel der Arbeit
Es sollen Möglichkeiten skizziert werden, wie perioperative Organschäden präventiv und proaktiv durch die Beeinflussung des „high mobility group box 1 protein (HMGB1) signaling“ vermieden und verringert werden können.
Material und Methoden
Es wurde eine MEDLINE-Suche im Bereich der klinischen und der Grundlagenforschung durchgeführt. Die Darstellung grundlegender Mechanismen perioperativer Organschäden und die Diskussion der Bedeutung von HMGB1 in der Prävention und Therapie mithilfe medikamentöser und nichtmedikamentöser Intervention stehen im Mittelpunkt der Betrachtung.
Ergebnisse
In der Pathogenese von septisch und aseptisch bedingten Organschäden ist HMGB1 ein zentrales Element. „Remote ischemic preconditioning“ (RIPC) und Dexmedetomidin sind hocheffektive Möglichkeiten, um Organschäden abzumildern resp. zu vermeiden.
Schlussfolgerung
Sowohl bei Ischämie-Reperfusionsschäden als auch bei inflammationsbedingten Organschäden bieten RIPC und Dexmedetomidin protektive Eigenschaften, die u. a. HMGB1-vermittelt sind. Hierdurch lassen sich Nieren, Herz, Lungen, Leber und Gehirn wirkungsvoll schützen. Die Anwendung dieser Konzepte sollte im klinischen Alltag Beachtung finden.
Abstract
Background
Acutely occurring organ damage significantly contributes to morbidity and mortality in the perioperative context.
Objective
This article highlights new clinical perspectives on how perioperative organ damage can be prevented and ameliorated by influencing the high mobility group box 1 protein (HMGB1) signaling.
Material and methods
A MEDLINE search was performed in the fields of clinical and basic research. The presentation of basic mechanisms of perioperative organ damage and the discussion of the importance of HMGB1 in prevention and treatment by pharmaceutical and nonpharmaceutical interventions are the focus of the review.
Results
The HMGB1 is a central element in the pathogenesis of septic and aseptic inflammation-induced organ damage. Remote ischemic preconditioning (RIPC) and dexmedetomidine are highly effective approaches to mitigate or prevent organ damage.
Conclusion
The RIPC and dexmedetomidine offer protective properties in ischemia-reperfusion injury as well as in inflammation-related organ damage, which are mediated by HMGB1, among others. This effectively protects the kidneys, heart, lungs, liver and brain. The application of these concepts should be considered in routine clinical practice.
Literatur
Nepogodiev D, Martin J, Biccard B, Makupe A, Bhangu A, National Institute for Health Research Global Health Research Unit on Global Surgery (2019) Global burden of postoperative death. Lancet 393:401. https://doi.org/10.1016/S0140-6736(18)33139-8
Lobo SM, Rezende E, Knibel MF, Silva NB, Paramo JA, Nacul FE, Mendes CL, Assuncao M, Costa RC, Grion CC et al (2011) Early determinants of death due to multiple organ failure after noncardiac surgery in high-risk patients. Anesth Analg 112:877–883. https://doi.org/10.1213/ANE.0b013e3181e2bf8e
Sauaia A, Moore EE, Johnson JL, Chin TL, Banerjee A, Sperry JL, Maier RV, Burlew CC (2014) Temporal trends of postinjury multiple-organ failure: still resource intensive, morbid, and lethal. J Trauma Acute Care Surg 76:582–592. https://doi.org/10.1097/TA.0000000000000147 (discussion 592–583)
Bainbridge D, Martin J, Arango M, Cheng D, Evidence-based Peri-operative Clinical Outcomes Research (2012) Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet 380:1075–1081. https://doi.org/10.1016/S0140-6736(12)60990-8
Ferdinandy P, Schulz R, Baxter GF (2007) Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev 59:418–458. https://doi.org/10.1124/pr.107.06002
Conrad C, Eltzschig HK (2020) Disease mechanisms of Perioperative organ injury. Anesth Analg 131:1730–1750. https://doi.org/10.1213/ANE.0000000000005191
Vachharajani V, McCall CE (2019) Epigenetic and metabolic programming of innate immunity in sepsis. Innate Immun 25:267–279. https://doi.org/10.1177/1753425919842320
Xue J, Suarez JS, Minaai M, Li S, Gaudino G, Pass HI, Carbone M, Yang H (2021) HMGB1 as a therapeutic target in disease. J Cell Physiol 236:3406–3419. https://doi.org/10.1002/jcp.30125
Torregroza C, Gnaegy L, Raupach A, Stroethoff M, Feige K, Heinen A, Hollmann MW, Huhn R (2021) Influence of hyperglycemia and diabetes on Cardioprotection by humoral factors released after remote Ischemic preconditioning (RIPC). Int J Mol Sci. https://doi.org/10.3390/ijms22168880
Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, Wolf B, Goebel U, Schwer CI, Rosenberger P et al (2015) Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA 313:2133–2141. https://doi.org/10.1001/jama.2015.4189
Meersch M, Kullmar M, Pavenstadt H, Rossaint J, Kellum JA, Martens S, Klausmeyer P, Schmidt EA, Kerschke L, Zarbock A (2020) Effects of Different Doses of Remote Ischemic Preconditioning on Kidney Damage Among Patients Undergoing Cardiac Surgery: A Single-Center Mechanistic Randomized Controlled Trial. Crit Care Med 48:e690–e697. https://doi.org/10.1097/CCM.0000000000004415
Moretti C, Cerrato E, Cavallero E, Lin S, Rossi ML, Picchi A, Sanguineti F, Ugo F, Palazzuoli A, Bertaina M et al (2018) The EUROpean and Chinese cardiac and renal remote Ischemic preconditioning study (EURO-CRIPS Cardiogroup I): a randomized controlled trial. Int J Cardiol 257:1–6. https://doi.org/10.1016/j.ijcard.2017.12.033
Otsuka H, Miyoshi T, Ejiri K, Kohno K, Nakahama M, Doi M, Munemasa M, Murakami M, Nakamura K, Ito H (2021) Possible protective effect of remote Ischemic preconditioning on acute kidney injury following elective Percutaneous coronary intervention: secondary analysis of a multicenter, randomized study. Acta Med Okayama 75:45–53. https://doi.org/10.18926/AMO/61433
Pierce B, Bole I, Patel V, Brown DL (2017) Clinical outcomes of remote Ischemic preconditioning prior to cardiac surgery: a meta-analysis of randomized controlled trials. J Am Heart Assoc. https://doi.org/10.1161/JAHA.116.004666
Deferrari G, Bonanni A, Bruschi M, Alicino C, Signori A (2018) Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials. Nephrol Dial Transplant 33:813–824. https://doi.org/10.1093/ndt/gfx210
Wu J, Yu C, Zeng X, Sun C (2021) The hepatoprotective effect from ischemia-reperfusion injury of remote ischemic preconditioning in the liver related surgery: a meta-analysis. ANZ J Surg. https://doi.org/10.1111/ans.17236
Zheng L, Han R, Tao L, Yu Q, Li J, Gao C, Sun X (2020) Effects of remote ischemic preconditioning on prognosis in patients with lung injury: a meta-analysis. J Clin Anesth 63:109795. https://doi.org/10.1016/j.jclinane.2020.109795
Sales AHA, Barz M, Bette S, Wiestler B, Ryang YM, Meyer B, Bretschneider M, Ringel F, Gempt J (2017) Impact of ischemic preconditioning on surgical treatment of brain tumors: a single-center, randomized, double-blind, controlled trial. BMC Med 15:137. https://doi.org/10.1186/s12916-017-0898-1
Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas JM et al (2016) Effect of Remote Ischaemic preconditioning on Clinical outcomes in patients undergoing Coronary Artery bypass graft surgery (ERICCA study): a multicentre double-blind randomised controlled clinical trial; Efficacy and Mechanism Evaluation Southampton (UK) (In)
Meybohm P, Kohlhaas M, Stoppe C, Gruenewald M, Renner J, Bein B, Albrecht M, Cremer J, Coburn M, Schaelte G et al (2018) RIPheart (remote Ischemic preconditioning for heart surgery) study: myocardial dysfunction, postoperative Neurocognitive dysfunction, and 1 year follow-up. J Am Heart Assoc. https://doi.org/10.1161/JAHA.117.008077
Kottenberg E, Thielmann M, Bergmann L, Heine T, Jakob H, Heusch G, Peters J (2012) Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol—a clinical trial. Acta Anaesthesiol Scand 56:30–38. https://doi.org/10.1111/j.1399-6576.2011.02585.x
MacAllister R, Clayton T, Knight R, Robertson S, Nicholas J, Motwani M, Veighey K (2015) REmote preconditioning for Protection Against Ischaemia-Reperfusion in renal transplantation (REPAIR): a multicentre, multinational, double-blind, factorial designed randomised controlled trial</i>; Efficacy and Mechanism Evaluation Southampton (UK) (In)
Veighey KV, Nicholas JM, Clayton T, Knight R, Robertson S, Dalton N, Harber M, Watson CJE, De Fijter JW, Loukogeorgakis S et al (2019) Early remote ischaemic preconditioning leads to sustained improvement in allograft function after live donor kidney transplantation: long-term outcomes in the REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) randomised trial. Br J Anaesth 123:584–591. https://doi.org/10.1016/j.bja.2019.07.019
Chen J, Jiang Z, Zhou X, Sun X, Cao J, Liu Y, Wang X (2019) Dexmedetomidine preconditioning protects Cardiomyocytes against hypoxia/Reoxygenation-induced Necroptosis by inhibiting HMGB1-mediated inflammation. Cardiovasc Drugs Ther 33:45–54. https://doi.org/10.1007/s10557-019-06857-1
Liu J, Shi K, Hong J, Gong F, Mo S, Chen M, Zheng Y, Jiang L, Xu L, Tu Y et al (2020) Dexmedetomidine protects against acute kidney injury in patients with septic shock. Ann Palliat Med 9:224–230. https://doi.org/10.21037/apm.2020.02.08
Bao N, Tang B (2020) Organ-protective effects and the underlying mechanism of Dexmedetomidine. Mediators Inflamm 2020:6136105. https://doi.org/10.1155/2020/6136105
Huang YQ, Wen RT, Li XT, Zhang J, Yu ZY, Feng YF (2021) The protective effect of Dexmedetomidine against Ischemia-Reperfusion injury after Hepatectomy: a meta-analysis of randomized controlled trials. Front Pharmacol 12:747911. https://doi.org/10.3389/fphar.2021.747911
Wang C, Yuan W, Hu A, Lin J, Xia Z, Yang CF, Li Y, Zhang Z (2020) Dexmedetomidine alleviated sepsisinduced myocardial ferroptosis and septic heart injury. Mol Med Rep 22:175–184. https://doi.org/10.3892/mmr.2020.11114
Mei B, Li J, Zuo Z (2021) Dexmedetomidine attenuates sepsis-associated inflammation and encephalopathy via central alpha2A adrenoceptor. Brain Behav Immun 91:296–314. https://doi.org/10.1016/j.bbi.2020.10.008
Cioccari L, Luethi N, Bailey M, Shehabi Y, Howe B, Messmer AS, Proimos HK, Peck L, Young H, Eastwood GM et al (2020) The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the sedation practice in intensive care evaluation [SPICE III] trial. Crit Care 24:441. https://doi.org/10.1186/s13054-020-03115-x
Hegazy MA, Hegazi RA, Hendawy SR, Hussein MS, Abdellateef A, Awad G, Abdeldayem OT (2020) Cardiac preconditioning effect of Ketamine-Dexmedetomidine versus Fentanyl-Propofol during arrested heart Revascularization. Anesth Essays Res 14:312–320. https://doi.org/10.4103/aer.AER_55_20
Cho JS, Shim JK, Soh S, Kim MK, Kwak YL (2016) Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int 89:693–700. https://doi.org/10.1038/ki.2015.306
Biccard BM, Goga S, de Beurs J (2008) Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials. Anaesthesia 63:4–14. https://doi.org/10.1111/j.1365-2044.2007.05306.x
Danksagung
Die Autoren danken Nina Knubel für die Hilfe beim Erstellen der Abbildungen.
Förderung
Diese Arbeit wurde unterstützt von der Deutschen Forschungsgemeinschaft (DFG RO 4537/5‑1 und ZA 428/18-1).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Interessenkonflikt
M. Lehmann, A. Zarbock und J. Rossaint geben an, dass kein Interessenkonflikt besteht.
Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.
Additional information
QR-Code scannen & Beitrag online lesen
Rights and permissions
About this article
Cite this article
Lehmann, M., Zarbock, A. & Rossaint, J. Neue Aspekte der perioperativen Organprotektion. Anaesthesiologie 71, 741–749 (2022). https://doi.org/10.1007/s00101-022-01197-6
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00101-022-01197-6