METHOXYFLURANE AS AN ANESTHETIC FOR NEUROLOGICAL SURGERY ALAN VAN POZNAK, M.D., BRONSON S. RAY, M.D., AND JOSEPH F. ARTUSIO, JR., M.D. DepartmeTit of Anesthesiology, The New York Hospital, a,d Department of Surgery (Anesthesiology), a~d Departme~t of Surgery (Neurosurgery), The New York Hospital, Cornell University Medical CoUege, New York, New York (Received for publication February ~4, 1960) HE most favorable physiologic conditions for anesthesia in neurosur- gery are provided bv diethyl ether, because it is least depressant to T respiratory function and maintains a stable cardiovascular system. The definite hazard of fire or explosion, particularly in the presence of the elec- trocautery, has influenced many neurosurgeons to accept anesthetic agents and techniques which, while providing nonflammability, nevertheless intro- duce the less favorable physiologic conditions inherent in the employment of multiple drug techniques. The main ingredient of the nonexplosive technique currently preferred by many neurosurgeons is nitrous oxide. However, because of its low potency there may be insufficient analgesia for many procedures, there is an in- creased hazard of hypoxia, and the patient frequently reacts on the endo- tracheal tube. In an attempt to compensate for the inadequacies of nitrous oxide, anesthetists have added intravenous drugs such as barbiturates, nar- cotics, and muscle relaxants, as well as inhalation anesthetics such as tri- chloroethylene (Trilene | Trimar | or halothane (Fluothane| Each of these supplements may produce unwanted effect on respiration or cir- culation. In an attempt to find a nonflammable anesthetic agent as innocuous as nitrous oxide but with greater potency, Van Poznak and Artusio 1-4 in 1956 began screening a number of fluorinated hydrocarbons and fluorinated ethers.* The most useful compound so far examined has been given the generic name methoxyflurane. It is 1,1-difluoro e,e-dichloro ethyl methyl ether, with the following structural formula: CH3-O-CF2CHC12. It is a clear, colorless liquid of characteristic odor. The boiling point is 103~ and the vapor pressure at e0~ is e5 mm. Hg. It is stable in the presence of light, soda, lime, and Baralyme | Presently available samples have dibenzylamine 0.01 per cent added as a stabilizer. At room temperature it is nonflammable in any mixture of air or oxygen. Pharmacologically, its behavior is in many ways similar to that of di- ethyl ether. Methoxyflurane can be administered by any technique used for diethyl ether, including open drop, semiclosed circle, and closed circle. A special vaporizer is not needed. It is compatible with other agents such as * Many of these compoumls were synthesized in tim laboratories of the Dow Chemical Company. 477 478 A. VAN POZNAK, B. S. RAY AND J. F. ARTUSIO, JR. thiopental, suceinylcholine, d-tuboeurarine, trimethaphan (Arfonad| ni- trous oxide, barbiturates, atropine, and scopolamine. It can also be used with hypothermia. With methoxyflurane alone, the time required for induction is about 9 minutes, and the time required until intubation is completed is about 14 minutes. In routine clinical practice induction and intubation are greatly speeded with the use of supplementary thiopental and succinylcholine. The conventional signs of depth of anesthesia as outlined by Guedel for diethyl ether are not as obvious with methoxyflurane and have been described by Artusio et al. 2 During maintenance in light to moderate levels with methoxy- flurane, respiration is full and even. There is usually slight depression of the blood pressure, which becomes further depressed with increasing depth of anesthesia. Trimethaphan (Arfonad | in the presence of methoxyflurane has a greater hypotensive effect than it does in the presence of other anes- thetics. The cardiac rhythm remains entirely regular. Pre-existing arrythmi- as have occasionally disappeared during methoxyflurane anesthesia. The cardiac rate usually slows slightly but the change is insignificant. Emergence requires about the same time as that from a comparable depth of diethyl

TABLE 1 First 100 ueurosurgical cases iu which methoxyflurane was used as anesthetic agent

Excision of brain tumors 14 Pituitary adenoma 3 Acoustic neurinoma 3 Meningioma 3 Cerebral glioma Posterior fossa tumor 3 Hypophysectomies ~2 Other craniotomies 11 Aneurysm Subdural hematoma 1 Cerebrospinal fluid fistula Cortical scar 1 Decompression foramen magnum 1 Osteomyelitis 1 Cranioplasty o Revision of wound 1 Fifth nerve operations 4 Spinal operations 31 Cord tmnor o Cervical disk Lumbar disk ~3 Chordotomy 3 Rhizotomy 1 Miscellaneous 18 Sympathectomy Peripheral nerve repair Arteriogram 13 Ventriculogram 1 -- Total 100