Freedman M D, Gal J, Freed C R
Eur J Clin Pharmacol. 1982;22(2):129-35. doi: 10.1007/BF00542457.
Accidental bolus administration of lidocaine ranging in dosages from 1000 mg to 2000 mg 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 100-200 ml/min. Hepatic clearance of lidocaine is 1000 ml/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 30 mg/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 30 min after lidocaine infusion. In the second group of eight dogs, an extracorporeal bypass pump was used for 90 min 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 3 mg/kg. Drug clearance was 39.75 +/- 4.16 ml/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.