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Halothane이 肝朦機能에 미치는 影響

Effects of Halothane on Hepatic Function in the Dog

대한마취과학회지 1968년 1권 1호 p.9 ~ 24
오흥근 (  ) - 연세대학교 의과대학 생리학교실 마취과학교실

Abstract


Since halothane, as a new potent, non-explosive, volatile agent, was introduced by Raventos(1956) and studied clinically by Johnstone(1958), Bryce-Smith (1958) and Stephen(1958), it has been used extensively all over the world. However recent case reports of liver necrosis following halothane anesthesia have raised the possibility that the agent may, under certain circumstance, damage the liver. Following the announcement of cooperative study of effects of halothane on the liver by the National Research Council Committee on anesthesia of U.S.A. in 1963, this investigation was undertaken.
Experiments were carried out in 31 anesthetized mongrel dogs, weighing approximately 10kg. After anesthesia with pentothal sodium (25mg/kg), an endotracheal tube with cuff was passed and connected to a closed circle absorption system using an Ohio Heidbrink machine. Oxygen flow was 300 to 500 ml/min. Fluotec Mark Ⅱ vaporizer, using 1.5 to 2% for induction and 0.5 to 1% for maintenance, was set up outside of the circle system. Depth of anesthesia was judged mainly by clinical signs eg. Respiration and blood pressure, and halothane anesthesia lasted for 3 hours. After laparotomy, a ligation of the cystic duct was done and bile was collected from the cannulated common bile duct continuously. Studies have been made on the cardiac output and hepatic blood flow with changes of blood pressure, bile formation, function of dye excretion, changes of serum protein, prothrombin time, coagulation time and histopathological changes of the liver. The results obtained may be summarized as follows.
1. Measuring of cardiac output using RIHSA after halothane administration with lowered blood pressure, as compared with investigations before halothane (average blood pressure 155mmHg), showed 12.4% decrease in light anesthesia (average B.P. 140mmHg) and 27% in deep anesthesia (average B.P. 7OmmHg).
2. Hepatic blood flow measured with radioactive colloidal gold(Au^(198)) showed 218 ml/min in the control group (B.P. 170mmHg) and 309 ml/min in the deep halothane anesthesia group (R.P. 80mmHg). Thus there was a 42% increase in deep halothane anesthesia. As the blood pressure decreased the cardiac output also decreased but the hepatic blood flow showed a tendency to increase.
3. The amount of bile flow an 1 cholate output in the pre-halothane state was 0.040 ml/min and 1.069 mg/min, respectively. After halothane administration, the bile was significantly increased to 0.061 ml/min at 90 min. Thereafter it returned to the initial level 3 hours later and cholate:output continuously decreased for 3 hrs., showing that halothane may have a hydrocholeretic effect. Before and after the halothane administration, Po₂ in arteral blood was 344 and 377 mmHg, Pco₂ in arterial blood was 38.5 and 40. 9mmHg, respectively. The Po₂, Pco₂, Ph and electrolytes (sodium, potassium and chloride concentration) in the hepatic bile did not reveal a significant change. Electrolytes (sodium, potassium and chloride), and osmolarity in urine did not show significant changes.
4. The function of biliary dye excretion was studied using bromsulfalein (BSP), phenol red (PSP) and indocyanine green. The one hour biliary excretion of indocyanine green did not show significant changes between the control group, the group with exposure only, and the group with two exposures with an interval of 1 week. However, the biliary excretion of indocyanine green for 2 hours was 45% of the given amount for the control group, 41% for one exposure, and 37% for the group with two exposures. PSP biliary clearance, before and after halothane administration, showed 19.62 ml/min and 13.35 ml/min respectively, but BSP biliary clearances were 21.3 ml/min and 22.0 ml/min respectively. It is concluded that the biliary excretion of indocyanine green and PSP showed a tendency for a decrease following halothane administration.
5. The coagulal ion time and prothrombin time, measured after halothane administration, were -shortened during the first hour, and after this, they were gradually prolonged, returning to normal in two to three hours after the administration. The values of serum protein and thymol turbidity did not show significant differences among each group and between the time before and after halo-thane administration.
6. The histopathological examination showed that the anesthetic group had a much more intense degree of degenerative changes of liver parenchymal cells including vacuolar formation and hydropic degeneration, in addition to vasodilatation, compared with the biopsy before halothane.
7. The above studies indicate that halothane administration exerts a slight influence on the hepatic function and induces histological changes in the liver. However, quantitative comparison between halothane and other anesthetic drugs will be clarified by further studies.

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