Study On Forensic Toxicokinetics Of Lidocaine After The Epidural Anesthesia Accident (Ⅷ)

OBJECTIVE:1.To develop dynamic distribution models of lidocaine in rabbits after a subarachnoid space anesthesia.2.To study the toxicokinetics of lidocaine in rabbits after a subarachnoid space anesthesia with lidocaine hydrochloride.3.To investigate the dynamic distribution of lidocaine in rabbits which provides a scientific evidence for the forensic identification of the anesthesia accident caused by lidocaine.METHOD:1.Animal model:The rabbits in experiment group were given a subarachnoid space anesthesia with an even speed with 13.3mg/kg of lidocaine hydrochloride.Rabbits in control group were given eqaul NS repalced.2.GC and GC/MS:The samples were extracted with ether.Analysis was performed by a GC equipped with a NPD and a GC/MS.The qualitative analysis was based on retention time in the chromatographic system coupled with the ion fragmentation spectrum in the mass spectrometer.The quantitative analysis was on an internal standard method.3.Collection of samples:The rabbits were executed by aeroembolism in different times after administration.Brain,C.S.F,spinal cord(cervical spinal cord,thoracic spinal cord,lumbar spinal cord,sacrum spinal cord),heart,lung,liver,spleen,kidney,bile,urine,heart blood, peripheral blood,muscle of injected location and muscle of control were collected and detemined immediately.Compartment model and toxicokinetic parameters were assessed by WinNonLin program.RESULTS:1.The study had established dynamic distribution models of subarachnoid space anesthesia.The symptom of the rabbits in experiment group concides with the symptom of clinical anesthesia.2.The mean serum concentration-time profile of lidocaine after subarachnoid space administration to rabbits was fitted to a two-compartment open model with first order kinetics. The toxicokinetic equation was C_t=50.894198e^-0.226742t and toxicokinetic parameter was-K_10:0.227min^-1,t_1/2k10:3.057min,V:261.326L/kg,CL:59.254 L/kg/h,AUC:224.459, C_max,:50.894μg/ml.3.The concentrations value of C.S.F with the corresponding peripheral blood is between 30.1～45.9 in rabbits executed by aeroembolism within 1 hours.The concentrations of brain, C.S.F and spinal cord was lower in rabbits executed by aeroembolism within 2 hours.CONCLUSION:1.The model of lidocaine after a subarachnoid space anesthesia can provide a scientific evidence.2.The concentration of C.S.F,heart blood,peripheral blood,heart,liver,spleen,muscle of injected location reached maximum immediately after administration.The concentration of lung, bile,kidney,brain,urine and muscle of control increased first and then decreased.3.The concentration of brain,C.S.F and spinal cord was higher than others in rabbits executed by aeroembolism within 1 hours.The concentration of all organ and body fluids was lower in rabbits executed by aeroembolism within 2 hours than the rabbits executed by aeroembolism within 1 hours.The feature of distribution provides experimental evidence for anethesia accident.