[The pharmacokinetics of lidocaine in resuscitation conditions. Results of experimental studies on swine]

Abstract

To re-evaluate dosage requirements for i.v. and endobronchial (e.b.) lidocaine therapy under the conditions of cardiac arrest, we investigated the pharmacokinetics of lidocaine after i.v. and e.b. administration in an animal cardiopulmonary resuscitation (CPR) model. METHODS. We induced cardiac arrest by ventricular fibrillation in 16 normoventilated pigs under i.v. anesthesia. Resuscitation started after 3 min with resumed ventilation and internal cardiac compressions. Simultaneously, 8 animals received 10 micrograms epinephrine/kg and 2 mg lidocaine/kg via peripheral i.v. injection and another 8 received 100 micrograms epinephrine/kg and 2 mg lidocaine/kg via e.b. instillation. During CPR and the 1st hour of restored spontaneous circulation the ECG, heart rate, and mean arterial pressure were continuously recorded. Plasma concentrations of lidocaine were measured by gas chromatography in venous blood, which was collected automatically at intervals of 30 s. RESULTS. All animals were resuscitated successfully after 3.7 +/- 1.6 min (i.v.) and 3.8 +/- 1.1 min (e.b., means +/- SD). With no differences during CPR, the hemodynamic situation of the e.b. medicated animals was characterized by higher arterial pressures from 10-15 min and higher heart rates from 10-60 min of restored spontaneous circulation. Median maximum concentrations of lidocaine after i.v. (3.2 range 1.3-9.6 micrograms/ml) and e.b. administration (3.1 range 1.1-8.6) were measured after 5.5 min (range i.v. = 4-10 min, e.b. = 3-7 min). Mean concentrations within a therapeutic range of 2-5 micrograms/ml were reached after 2-3 min and remained within these limits for 20-25 min after both routes of administration. Individual lidocaine concentrations below the therapeutic level of 2 micrograms/ml were measured in one experiment after i.v. application and in three experiments after e.b. administration. The individual time concentration profiles were mathematically approximated using an open two - compartment model with first-order absorption. The absorption half-life of e.b. lidocaine was 3.9 min, and mean bioavailability was 90%. Elimination pharmacokinetics of i.v. and e.b. lidocaine were nearly identical, with elimination half-lives of 25 min (e.b.) and 42 min (i.v.). Total body clearances were 401 ml/min (e.b.) and 362 ml/min (i.v.). CONCLUSION. An i.v. bolus of lidocaine during CPR should not exceed 2 mg/kg. During CPR without i.v. access the e.b. instillation of lidocaine can be recommended, but to ensure therapeutic concentrations a minimum dosage of 2 mg/kg is suggested.