| Abstract: |
The present study has been performed in the departments of Anesthesia, Pharmacology and Clinical Pathology, Faculty of Medicine, Zagazig University. The aim of the study was a trial to evaluate the clinical and pharmacological effects ofsevoflurane. This study included two main parts, pharmacological experimental part and clinical part.In the pharmacological experimental part, total 207 normal adult albino rats were used as an animal model. This part was divided into 3 main studies, toxicity study, hemodynamic study and neuromuscular study.In the toxicity study, total I26 normal adult albino rats were used in this study which was divided into two studies:(a) Studying the effects of graded concentrations of sevoflurane for variable durations. This study was containing 90 rats divided into 3 groups, each of 24 rats (divided into 4 sub-groups each of 6 rats) and a control group of I 8 rats.(b) Studying the effects of repeated administration of 2% of sevoflurane after 2 days. This study was containing 30 rats divided into 4 groups and a control group, each group of 6 rats.The parameters studied were:• Time of onset of anesthesia and time of recovery.• Recording of any abnormality.xBiochemical blood analysis for evaluating liver and kidney function by measuring blood urea nitrogen, serum creatinine, AST, ALT, ALP, T Bil and D Bil. pre-exposure(control), immediately post- exposure and after 24 hours.Histo-pathological study of heart, lung, liver and kidney after 24 hours.In the hemodynamic study, total 36 normal adult albino rats were used to study the effect of sevoflurane inhalation on the arterial blood pressure and heart rate. The rats were divided into 5 groups and a control group each of 6 rats.In the neuro-muscular study, total 45 rats were used to study the effect of sevoflurane and its interaction with atracurium and gallamine on gastrocnemius-sciatic nerve preparation. The rats were divided into 7 groups, six groups, each of 5 rats, while the seventh group was 15 rats.The results of this part showed that:l-The onset of anesthesia and the time of recovery were affected by the concentration and the duration of exposure to sevoflurane.2-Labored breathing was noticed with high concentration and long duration.3-Renal and hepatic toicity with sevoflurane in rats depending on the concentration of the sevoflurane and the duration of exposure.4-Repeated administration of 2% concentration of sevoflurane after 2 days did not cause any renal or hepatic change.5-Sevoflurane in graded concentrations produced significant concentration-dependent drop in the blood pressure. Also, sevoflurane elicited in-significant decrease in the heart rate in proportion with the inhaled concentration.6-Concentrations of 4% and 6% of sevoflurane alone caused reduction of the twitch tension returned to normal within 5-7 minutes. Administration of atracurium with sevoflurane produced proportional reduction in the twitch tension induced by indirect electrical stimulation of the gastrocnemius sciatic nerve preparation. All values of ED50 of atracurium were decreased by sevoflurane inhalation. This shows increase of potency of atracurium with sevoflurane. Also, inhalation of sevoflurane produced significant prolongation in recovery time from atracurium.Inhalation of sevoflurane caused no significant change in the mean percentage of reduction produced by sub-maximal dose of gallamine. However, it elicited increase in recovery time up to 100%, which was significant after inhalation of sevoflurane.In the clinical part, 60 adult patients of both sexes class 1 and 11 of American• Society of Anesthesiologists (ASA) classification, undergoing elective surgery, divided into two equal groups (1 and 11):In Group 1, anesthesia was induced by thiopentone sodium 3-5 mg/kg, and intubation done with succinylcholine 1 mg/kg. Anesthesia was maintained by sevoflurane 1-1.5% concentration with oxygen 8 L/minute and pancronium bromide 0.2 mg/kg was injected with controlled ventilation. Injection of atropine 1 mg with prostigmin 2.5mg to reverse the effect of pancronium. The duration of operations in this group was from 1 up to 5 hours.While, in group II, the same induction of anesthesia done as group I but, anesthesia was maintained by sevojlurane 2-3% concentration with oxygen 8 L/minute with spontaneous ventilation. The duration of operations in this group were from 1;2 to I hour.Pre-operative, intra-operative and post-operative comparison of the following parameters done:I-Heart rate, blood pressure (systolic, diastolic and mean) and ECG. 2- Kidney function (blood urea nitrogen and serum creatinine).3- Liver enzymes (AST, ALT, ALP, T. Bil and D.Bil).4-The recovery characteristics, (eye opening, square fingers, spontaneous breathing, extubation, state name, nausea, and vomiting) were observed and recorded.The results of this part showed that:I-Sevojlurane caused in-significant decrease in heart rate, systolic, diastolic and mean blood pressure and may do prolongation of Q- T interval in E. C. G. intra-operatively mainly in females.2-Blood urea nitrogen and serum creatinine in-significantly decreased intra-operative and post-operative.3-ln-significant increase of AST, ALl, T Bil and D Bil while ALP decreased post-operatively.4-Recovery after sevojlurane anesthesia was rapid especially with the short duration operations. Post-operative nausea and vomiting in 31.6%from the total patients in both groups occurred.
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