Lokal Anestezik Sistemik Toksisitesi (LAST) ve Güncel Yaklaşımlar
Özet
Lokal Anestezik Sistemik Toksisitesi (LAST), lokal anesteziklerin yanlışlıkla damar içine enjekte edilmesi veya sistemik dolaşıma hızlı emilimi sonucu gelişen, nadir fakat hayati risk taşıyan bir komplikasyondur. Bu ajanlar temel olarak sodyum kanallarını bloke ederek çalışır; ancak yüksek plazma konsantrasyonları merkezi sinir sistemi (MSS) ve kardiyovasküler sistem (KVS) üzerinde toksik etkiler yaratarak mitokondriyal metabolizmayı ve iyon sinyallerini bozar. Klinik tablo genellikle ağızda metalik tat ve kulak çınlaması gibi öncü belirtilerle başlar, ardından nöbetler ve kardiyovasküler çöküşe kadar ilerleyebilir. Bununla birlikte, vakaların yaklaşık yarısında sadece KVS veya MSS bulguları içeren atipik seyirler görülebilir. Risk faktörleri arasında uç yaş grupları (bebekler ve yaşlılar), gebelik, kalp yetmezliği ve karaciğer veya böbrek disfonksiyonu yer alır. Korunma stratejileri; minimum etkin dozun kullanılmasını, kademeli enjeksiyonu ve damar içi ponksiyon riskini azaltan ultrason rehberliğini içerir. Tedavide ilk adım, lokal anestezik uygulamasının durdurulması ve asidozu önlemek için havayolu yönetimidir. Kesin tedavi yöntemi, lokal anesteziği hedef organlardan uzaklaştırarak bir "mekik" görevi gören %20’lik lipid emülsiyonu terapisidir. Olay sonrası hastaların 2-6 saat izlenmesi hayati önem taşır.
Local Anesthetic Systemic Toxicity (LAST) is a rare but potentially fatal complication resulting from accidental intravascular injection or rapid systemic absorption of local anesthetics. These agents primarily work by blocking sodium channels; however, high plasma concentrations interfere with mitochondrial metabolism and ion signaling, leading to toxic effects in the central nervous (CNS) and cardiovascular systems (CVS). Clinical presentation often begins with prodromal symptoms such as metallic taste or tinnitus, progressing to seizures and potential cardiovascular collapse. Notably, nearly half of all cases involve atypical presentations with isolated CVS or CNS symptoms. Risk factors include extreme age (infants and the elderly), pregnancy, heart failure, and hepatic or renal dysfunction. Prevention focuses on using the minimum effective dose, incremental injection, and utilizing ultrasound guidance to reduce the risk of vascular puncture. Management requires immediate cessation of the local anesthetic and prioritized airway management to prevent acidosis. The definitive treatment is the early administration of 20% lipid emulsion therapy, which acts as a "shuttle" to redirect local anesthetics away from target organs. Continuous monitoring for 2–6 hours post-event is essential for patient safety.
Referanslar
Neal JM, Barrington MJ, Fettiplace MR, et al. The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017. Reg Anesth Pain Med. 2018;43(2):113-123. doi:10.1097/AAP.0000000000000720
Pachuk CJ, Ciccarelli RB, Samuel M, et al. Characterization of a new class of DNA delivery complexes formed by the local anesthetic bupivacaine. Biochim Biophys Acta. 2000;1468(1-2):20-30. doi:10.1016/s0005-2736(00)00242-x
Chen D, Yan Y, Xie J, et al. Amide-type local anesthetics may suppress tumor cell proliferation and sensitize Human Hepatocellular Carcinoma Cells to Cisplatin via upregulation of RASSF1A expression and demethylation. J Cancer. 2020;11(24):7312-7319. Published 2020 Oct 23. doi:10.7150/jca.46630
Freeman J, Crowley PD, Foley AG, et al. Effect of Perioperative Lidocaine and Cisplatin on Metastasis in a Murine Model of Breast Cancer Surgery. Anticancer Res. 2018;38(10):5599-5606. doi:10.21873/anticanres.12894
Gitman M, Fettiplace MR, Weinberg GL, Neal JM, Barrington MJ. Local Anesthetic Systemic Toxicity: A Narrative Literature Review and Clinical Update on Prevention, Diagnosis, and Management. Plast Reconstr Surg. 2019;144(3):783-795. doi:10.1097/PRS.0000000000005989
Tunney RK Jr, Whyte K, DeAntonio HJ. Lidocaine toxicity in the setting of HeartMate II left ventricular assist device. J Clin Pharm Ther. 2018;43(5):733-736. doi:10.1111/jcpt.12717
Kramer ME, Holtan EE, Ives AL, Wall RT. Perioperative Intravenous Lidocaine Infusion Adverse Reaction: A Case Report. A A Pract. 2019;13(3):96-98. doi:10.1213/XAA.0000000000001002
Digala LP, Lucchese S. IV Lidocaine Infusion Leading to the Toxic Levels in Serum Causing Asystole - A Case Report. Headache. 2020;60(1):269-270. doi:10.1111/head.13699
Macfarlane AJR, Gitman M, Bornstein KJ, El-Boghdadly K, Weinberg G. Updates in our understanding of local anaesthetic systemic toxicity: a narrative review. Anaesthesia. 2021;76 Suppl 1:27-39. doi:10.1111/anae.15282
Brown DL, Ransom DM, Hall JA, Leicht CH, Schroeder DR, Offord KP. Regional anesthesia and local anesthetic-induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg. 1995;81(2):321-328. doi:10.1097/00000539-199508000-00020
Barrington MJ, Kluger R. Ultrasound guidance reduces the risk of local anesthetic systemic toxicity following peripheral nerve blockade. Reg Anesth Pain Med. 2013;38(4):289-299. doi:10.1097/AAP.0b013e318292669b
Auroy Y, Benhamou D, Bargues L, et al. Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service [published correction appears in Anesthesiology. 2003 Feb;98(2):595. Mercier Frédéric [corrected to Mercier Frédéric J]]. Anesthesiology. 2002;97(5):1274-1280. doi:10.1097/00000542-200211000-00034
Ecoffey C, Lacroix F, Giaufré E, Orliaguet G, Courrèges P; Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (ADARPEF). Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF). Paediatr Anaesth. 2010;20(12):1061-1069. doi:10.1111/j.1460-9592.2010.03448.x
Vasques F, Behr AU, Weinberg G, Ori C, Di Gregorio G. A Review of Local Anesthetic Systemic Toxicity Cases Since Publication of the American Society of Regional Anesthesia Recommendations: To Whom It May Concern. Reg Anesth Pain Med. 2015;40(6):698-705. doi:10.1097/AAP.0000000000000320
Gitman M, Barrington MJ. Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries. Reg Anesth Pain Med. 2018;43(2):124-130. doi:10.1097/AAP.0000000000000721
Kotelko DM, Shnider SM, Dailey PA, et al. Bupivacaine-induced cardiac arrhythmias in sheep. Anesthesiology. 1984;60(1):10-18. doi:10.1097/00000542-198401000-00004
Singaravelu Ramesh A, Boretsky K. Local anesthetic systemic toxicity in children: a review of recent case reports and current literature. Reg Anesth Pain Med. 2021;46(10):909-914. doi:10.1136/rapm-2021-102529
Gupta RK, Schwenk ES. Local anesthetic systemic toxicity in children: a review of recent case reports and current literature - an infographic. Reg Anesth Pain Med. 2021;46(10):915. doi:10.1136/rapm-2021-102993
El-Boghdadly K, Chin KJ. Local anesthetic systemic toxicity: Continuing Professional Development. Can J Anaesth. 2016;63(3):330-349. doi:10.1007/s12630-015-0564-z
El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives. Local Reg Anesth. 2018;11:35-44. Published 2018 Aug 8. doi:10.2147/LRA.S154512
Waldinger R, Weinberg G, Gitman M. Local Anesthetic Toxicity in the Geriatric Population. Drugs Aging. 2020;37(1):1-9. doi:10.1007/s40266-019-00718-0
Paqueron X, Boccara G, Bendahou M, Coriat P, Riou B. Brachial plexus nerve block exhibits prolonged duration in the elderly. Anesthesiology. 2002;97(5):1245-1249. doi:10.1097/00000542-200211000-00030
Grigg E, Anderson C, Pankovich M, Martin L, Flack S. Systemic ropivacaine toxicity from a peripheral nerve infusion in a medically complex patient. J Clin Anesth. 2015;27(4):338-340. doi:10.1016/j.jclinane.2015.03.021
Calenda E, Baste JM, Hajjej R, Danielou E, Peillon C. Toxic plasma concentration of ropivacaine after a paravertebral block in a patient suffering from severe hypoalbuminemia. J Clin Anesth. 2014;26(2):149-151. doi:10.1016/j.jclinane.2013.11.008
Wong GK, Joo DT, McDonnell C. Lipid resuscitation in a carnitine deficient child following intravascular migration of an epidural catheter. Anaesthesia. 2010;65(2):192-195. doi:10.1111/j.1365-2044.2009.06131.x
Wong GK, Crawford MW. Carnitine deficiency increases susceptibility to bupivacaine-induced cardiotoxicity in rats. Anesthesiology. 2011;114(6):1417-1424. doi:10.1097/ALN.0b013e31821a8d46
Pihlajamäki K, Kanto J, Lindberg R, Karanko M, Kiilholma P. Extradural administration of bupivacaine: pharmacokinetics and metabolism in pregnant and non-pregnant women. Br J Anaesth. 1990;64(5):556-562. doi:10.1093/bja/64.5.556
Tsen LC, Tarshis J, Denson DD, Osathanondh R, Datta S, Bader AM. Measurements of maternal protein binding of bupivacaine throughout pregnancy. Anesth Analg. 1999;89(4):965-968. doi:10.1097/00000539-199910000-00027
Santos AC, DeArmas PI. Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes. Anesthesiology. 2001;95(5):1256-1264. doi:10.1097/00000542-200111000-00033
Tran DQ, Boezaart AP, Neal JM. Beyond Ultrasound Guidance for Regional Anesthesiology. Reg Anesth Pain Med. 2017;42(5):556-563. doi:10.1097/AAP.0000000000000628
Fencl JL. Guideline implementation: local anesthesia. AORN J. 2015;101(6):682-692. doi:10.1016/j.aorn.2015.04.014
Abrahams MS, Aziz MF, Fu RF, Horn JL. Ultrasound guidance compared with electrical neurostimulation for peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials. Br J Anaesth. 2009;102(3):408-417. doi:10.1093/bja/aen384
Neal JM. Ultrasound-Guided Regional Anesthesia and Patient Safety: Update of an Evidence-Based Analysis. Reg Anesth Pain Med. 2016;41(2):195-204. doi:10.1097/AAP.0000000000000295
Aggarwal N. Local anesthetics systemic toxicity association with exparel (bupivacaine liposome)- a pharmacovigilance evaluation [published correction appears in Expert Opin Drug Saf. 2018 Jun;17(6):655]. Expert Opin Drug Saf. 2018;17(6):581-587. doi:10.1080/14740338.2017.1335304
Neal JM, Bernards CM, Butterworth JF 4th, et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35(2):152-161. doi:10.1097/AAP.0b013e3181d22fcd
Neal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version. Reg Anesth Pain Med. 2021;46(1):81-82. doi:10.1136/rapm-2020-101986
Wang QG, Wu C, Xia Y, et al. Epinephrine Deteriorates Pulmonary Gas Exchange in a Rat Model of Bupivacaine-Induced Cardiotoxicity: A Threshold Dose of Epinephrine. Reg Anesth Pain Med. 2017;42(3):342-350. doi:10.1097/AAP.0000000000000541
Neal et al Publication or reproduction of the checklist for commercial use requires written permission from ASRA. Graphic: Erin J. Neal. ACLS, Advanced Cardiac Life Support; LAST, Local Anesthetic Systemic Toxicity.
Fettiplace MR, Weinberg G. The Mechanisms Underlying Lipid Resuscitation Therapy. Reg Anesth Pain Med. 2018;43(2):138-149. doi:10.1097/AAP.0000000000000719
Fettiplace MR, Lis K, Ripper R, et al. Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. J Control Release. 2015;198:62-70. doi:10.1016/j.jconrel.2014.11.018
Dureau P, Charbit B, Nicolas N, Benhamou D, Mazoit JX. Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. Anesthesiology. 2016;125(3):474-483. doi:10.1097/ALN.0000000000001230
Shi K, Xia Y, Wang Q, et al. The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats [published correction appears in Anesth Analg. 2013 Aug;117(2):536]. Anesth Analg. 2013;116(4):804-809. doi:10.1213/ANE.0b013e318284123e
Fettiplace MR, Ripper R, Lis K, et al. Rapid cardiotonic effects of lipid emulsion infusion*. Crit Care Med. 2013;41(8):e156-e162. doi:10.1097/CCM.0b013e318287f874
Stehr SN, Ziegeler JC, Pexa A, et al. The effects of lipid infusion on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart. Anesth Analg. 2007;104(1):186-192. doi:10.1213/01.ane.0000248220.01320.58
Kawaraguchi Y, Roth DM, Patel HH. From local to global: lipid emulsion (intralipid) makes a move. Anesthesiology. 2011;115(2):226-228. doi:10.1097/ALN.0b013e318223b8f4
Willis-Gray MG, Husk KE, Brueseke TJ, Connolly A, Geller EJ. Lidocaine Use in Vaginal Surgery and Risk of Toxicity. Female Pelvic Med Reconstr Surg. 2020;26(9):546-549. doi:10.1097/SPV.0000000000000622
Partownavid P, Umar S, Li J, Rahman S, Eghbali M. Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats. Crit Care Med. 2012;40(8):2431-2437. doi:10.1097/CCM.0b013e3182544f48
