Investigation of intracerebroventricularly administered rocuronium's effects on central nervous system and epileptic dose in rats

SUMMARYInvestigation of Intraserebroventricularly Administered Rocuronium?s Effects onCentral Nervous System and Epileptic Dose in RatsDr. Mehmet Baykal, Dokuz Eylul University Medical Faculty, Department ofAnesthesiology and ReanimationObjective: Rocuronium can pass to CSF after intravenous administration. Rocuronium wasgiven into central nervous system through caudal way accidentally.We couldn?t find a studyin the recent literature investigating the potential effects of rocuronium in CSF. The aim ofthis study was to investigate the effects of intraserebroventricularly administered rocuroniumon central nervous system and to determine epileptic seizure producing dose of rocuroniumin rats.Method: After aproval of Dokuz Eylul University Medical Faculty Laboratory AnimalsResearch Ethics Committee, 200-350 g weighting, 18-24 months old 36 female Wistar-Albinorat was included in the study. A canula was placed intracerebroventricularly to all rats inorder to reach lateral ventricle. The study was designed in two phases. At the first phase,Rocuronium bromid ( 0.016 μmol in 10 μliters) was administered by divided doses of 5μliters using Hamilton syringe to Group Rocuronium ( n= 6). Each dose was injected in 60seconds and the effects on subjects were observed through 60 seconds. When tonic clonicseisures observed the total dose that was given to these rats was recorded. In the secondphase, Group 2 ( n= 6), Group 3 ( n= 6), Group 4 ( n= 6) were formed by using the doses of1/5, 1/10 and 1/100 of the obtained threshold dose respectively. In the Group 2 and Group 3extremity posture formation, contractions throughout the body, agitation and shivering wasobserved, whereas in the Group 4 locomotor activity lessening was observed. In Group 1(n=6), 10 microliters of a mixture of Ringer lactate and acetic acid which was at the same pHwith rocuronium solution was given to rats in order to examine the impact of pH. Statisticalanalysis was performed by Friedman and Wilcoxon test for comparing in group, and byKruskall-Wallis, Mann-Whitney U test and Fisher Exact test for comparing between groups.Results: The seizure threshold value of intraserebrovenricularly administrated Rocuronium0.056 ± 0.009 μmol in group rocuronium,. Totallybromid (pH = 3.6 ) was found asadministered volume was found as 35.0 ± 5.48 μliters. By rating epileptic seizure thresholdvalue of the rats to their mean body weight was calculated as 0.286 μmol/kg. At the dose of1/5 of seizure threshold dose, mostly extremity posture formation and contractions throughoutthe body was observed, whereas at the dose of 1/10 of seizure threshold dose agitation andshivering was observed. At the dose of 1/ 100 of seizure threshold dose, locomotor activitylessening was developed. All these effects were decreased progressively approximately in 1hour and persisted as decreased locomotor activity. The observation was continued for 6hours and within this time feeding and motor behaviours of the rats became similar with thecontrol group.Conclusion: The finding of our study suggested that, rocuronium is effective on centralnervous system in experimental rat model. Rocuronium can produce both excitatory effectsand epileptic seizures as dose dependently.