MS

thesisThe search for new general anesthetic agents has continued in spite of the many agents that are available because all have some problem with their use. The introduction of electrocautery has greatly reduced the use of flammable agents, primarily fluroxene, cyclopropane, and diethyl ether. Of the non-flammable agents' trichloroethylene is used during labor but rarely for surgery because of poor relaxation, myocardial and respiratory depression at anesthetic levels and the fact that it forms toxic products with soda lime. Nitrous oxide suffers from a lack of potency and must be given in high concentration with supplementary agents thus limiting the amount of oxygen available. Halothane is associated with the occasional occurrence of hepatic necrosis through to be a hypersensitivity reaction; and methoxyflurane can cause a high output renal failure probably due to toxicity of the fluoride ion. There is, therefore, a need for a new non-flammable anesthetic agent without these problems. The search for new agents has centered among the halogenated hydrocarbons because these are the non-flammable agents. Bromine and chlorine increase anesthetic potency while fluoride decreases flammability and increases stability of the molecule. Of the halogenated hydrocarbons only the aliphatic hydrocarbons and ethers have been found useful. The ethers have been studied recently because they depress the myocardium less, sensitize the conducting tissues of the heart less, and are less hepatotoxic. Enflurane, a halogenated methyl ethyl ether, was the subject of this investigation. It has the following characteristics: non-flammable, vapor pressure 180 mmHg at 20°C, blood gas partition coefficient 1.01, minimum alveolar concentration 1.68% (12.8 mmHg), induction concentration 0.5-4%, and is stable without preservative. In this study we found that it gives a rapid induction without complication. Cardiovascular and respiratory depression has parallel anesthetic depth. Cardiac rhythm is extremely stable and muscle relaxation is good. Emergence from anesthesia is rapid and smooth with stable vital signs and minimal occurrence of nausea, vomiting, delirium, and shivering. There is minimal post-operative pain relief. The only complication has been the occasional occurrence of twitching or tonic clonic movements during deep enflurane anesthesia with hyper-ventilation. This occurred once in 200 cases in our series. Extensive laboratory tests were done in 50 patients to look for evidence of hepatic or renal toxicity. Of the liver function tests there was a rise in BSP, SGOT, LDH, and bilirubin with the SGOT rising slightly above normal and the BSP becoming slightly more abnormal. There was no change in alkaline phosphatase, serum proteins, prothrombin time or percentage of eosinophils in the differential white blood count. These results were found to be similar to those reported after all potent inhalation anesthetics and after spinal anesthesia. Tests of renal function including BUN, creatinine, uric acid, serum electrolytes, and urine specific gravity showed no change from preoperative values and urine volume was within normal limits. We, therefore, found no evidence of hepatic or renal toxicity in our study. Cardiovascular effects of enflurane were studied in 21 patients using the pulse-pressure method of Warner. We compared awake values with those obtained at the level of enflurane supplying adequate pain relief during a period of full surgical stress (enflurane 1.1% N2O-O2 40%). Enflurane caused a statistically significant reduction in cardiac output (18%), stoke volume (12%), systolic pressure (10%), mean pressure (8%), and a significant rise in central venous pressure (43%) with no significant change in heart rage (-2%), peripheral resistance (+5%), or diastolic pressure (-4%). This work confirms the findings of others that enflurane depresses the myocardium. This depression is shown in the fall of cardiac output as a result of decreased stroke volume. The increase central venous pressure may also indicate depression of the myocardium