Summary
Accidental bolus administration of lidocaine ranging in dosages from 1000mg to 2000mg has caused death in humans. Because lidocaine clearance depends upon hepatic blood flow, drug clearance in a hypotensive overdosed patient is poor so that a drug overdose is likely to be irreversible. Traditional approaches to drug removal include hemodialysis and charcoal hemoperfusion. Neither treatment would be effective for lidocaine overdose because the drug is a myocardial depressant and because the clearance rates of these techniques are 100–200ml/min. Hepatic clearance of lidocaine is 1000ml/min in a human with normal cardiac output. We have tested a new concept for removal of high clearance drugs that are associated with myocardial depression. Cardiac bypass support was used in a dog experiment to demonstrate that restoration of cardiac output could restore high clearance of lidocaine. Sixteen anesthetized dogs were given 30mg/kg boluses of lidocaine. In one group of eight dogs, toxicity was treated with antiarrhythmic drugs, pressor drugs and cardioversion. Six out of eight of these animals died within 30min after lidocaine infusion. In the second group of eight dogs, an extracorporeal bypass pump was used for 90min after the lidocaine injection. None of these assisted animals died. Drug clearance in dogs treated with the extracorporeal pump was compared to drug clearance in eight dogs that received non-toxic lidocaine doses of 3mg/kg. Drug clearance was 39.75±4.16ml/kg/min in the overdosed animals compared to 38.29±8.6 ml/kg/min in the non-toxic animals. Thus, drug clearance was normal in dogs treated with the extracorporeal pump. These experiments suggest that short-term support of the circulation with an extracorporeal pump could theoretically be effective in reducing patient mortality from acute massive lidocaine overdose.
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References
Burlington B, Freed CR (1980) Massive overdose and death from prophylactic lidocaine. J Am Med Assoc 243:1035
Finkelstein F, Kreeft J (1979) Massive lidocaine poisoning. N Engl J Med 301: 50
Mayer PP (1972) Lidocaine overdose and ampoule labelling. Br Med J 3: 291
Beckett AH, Boyes RN, Appleton PJ (1966) The metabolism and excretion of lignocaine in man. J Pharm Pharmacol 18: 76S-81S
Frieden J (1965) Lidocaine as an antiarrhythmic agent. Am Heart J 70: 713–715
Grossman JI, Lubow LA, Frieden J, Rubin IL (1968) Lidocaine in cardiac arrhythmias. Arch Int Med 121: 396–401
Austen WG, Moran JM (1965) Cardiac and peripheral vascular effects of lidocaine and procainamide. Am J Cardiol 16: 701–707
Collinsworth KA, Kalman SM, Harrison DC (1974) The clinical pharmacology of lidocaine as an antiarrhythmic drug. Circulation 50: 1217–1230
deJong RH, Heavner JE (1971) Diazepam prevents local anesthetic seizures. Anesthesiology 34: 523–531
Steinhaus JE (1957) Local anesthetic toxicity: A pharmacological re-evaluation. Anesthesiology 18: 275–281
Stenson RE, Constantino RT, Harrison DC (1971) Interrelationships of hepatic blood flow, cardiac output and blood levels of lidocaine in man. Circulation 43: 205–211
Thomson PD, Rowland M, Melmon KL (1971) The influence of heart failure, liver disease and renal failure on the disposition of lidocaine in man. Am Heart J 82: 417–421
Gal J, Freedman M, Kumar E, Freed CR (1981) A rapid and simple microassay for lidocaine in human blood plasma using gas liquid chromatography with nitrogen detection. Ther Drug Mon 3: 177–180
Brennan FJ, Wit AL (1973) Effects of lidocaine on electrophysiological properties of Purkinje fibers surrounding acute myocardial infarction. Circulation 48: 148
Jewitt DE, Kishon Y, Thomas M (1968) Lignocaine in the management of arrhythmias after acute myocardial infarction. Lancet 1: 266–270
Lichstein E, Chadda KD, Gupta PK (1973) Atrioventricular block with lidocaine therapy. Am J Cardiol 31: 277–281
Lieberman NA, Harris RS, Katz RI, Lipschutz HM, Dolgin M, Fischer VJ (1968) The effects of lidocaine on the electrical and mechanical activity of the heart. Am J Cardiol 22: 375–380
Robison SL, Schroll, M, Harrison DC (1969) The circulatory response to lidocaine in experimental myocardial infarction. Am J Med Sci 258: 260–269
Branch RA, Shand DG, Wilkinson GR, Nies AS (1973) The reduction of lidocaine clearance by dl-propranolol: An example of hemodynamic drug interaction. J Pharm Exp Ther 184: 515–519
Benowitz N, Rowland M, Forsyth R, Melmon KL (1973) Circulatory influences of lidocaine disposition. Clin Res 21: 467
Hoffbrand BI, Forsyth RP (1973) Regional blood flow changes during norepinephrine, tyramine and methoxamine infusions in the unanesthetized rhesus monkey. J Pharm Exp Ther 184: 656–661
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This work was supported by a grant from Abbott Laboratories and by U.S. Public Health Service grants GM07063, NS09100, HL20194, and an RCDA HL00782 (CRF)
Editorial's Remarks: According to our editorial rules this journal does not accept experimental studies in animals. In the following paper an exception seems to be justified, in so far as the study suggests a new approach to the treatment of certain intoxications in man. F.G. and H.J.D.
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Freedman, M.D., Gal, J. & Freed, C.R. Extracorporeal pump assistance — Novel treatment for acute lidocaine poisoning. Eur J Clin Pharmacol 22, 129–135 (1982). https://doi.org/10.1007/BF00542457
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DOI: https://doi.org/10.1007/BF00542457