Test Avoids Fatal Anesthetic Reaction

A mysterious fatal reaction to anesthetics which has killed unknown numbers of patients across the world since the advent of general anesthesia can be eliminated by a single, simple blood test. University scientists reported on their efforts in narrowing down the cause of malignant hyperpyrexia, which has puzzled and frustrated surgeons and anesthesiologists for decades. Until recently, there has been no way to predict or prevent the disease. The rare, nearly always fatal reaction is indicated by the body temperature that rises to the deadly level of 110 degrees. It strikes without warning, usually in surgery recovery rooms after the patient has undergone general anesthisia. To those susceptible, general anesthetics such as ether, hallothane or nitrous oxide are literally poison to their systems. They all have the same effect - a rapidly rising temperaure, followed by stiffening of the muscles almost like rigor mortis, trembling and convulsions, rapid heartbeat and then death. Except in the case of very young patients, physicians are nearly always powerless to halt the fatal sequence once it strarts. The cause, according to four investigators in the U-M departments of anesthesiology and hematology, is abnormally high levéis in blood and muscle of a common enzyme - creatine phosphokinase (CPK). The members of the U-M reserch team are : Dr. Elemer K. Zsigmond, M. D., professor of anesthesiology; Dr. Gregory S. Duboff, DSC, research associate, U-M Simpson Memorial Institute ; William Starkweather, biochemist, Ann Arbor Veteran's Hospital; and Kathryn Flynn, laboratory technologist in anesthesiology. Persons subject to hyperpyrexia may have a CPK blood level 10 times normal. Prevention is through a complete ban on general anesthesia for persons with high CPK levéis in their blood not attributable to another cause. There is no way to lower the body's CPK level, Dr. Duboff said. Local anesthetic I injections or spinal blocks I will have to be used for 1 gery. How will doctors know I whom to test for CPK? The U-M investigation has I linked the susceptibility tol 'nyperpyrexia to genetic muscle disorders. Parallel, independent research in Great Britain has also disclosed recently the relationship between blood CPK levéis and hyperpyrexia. UM research went another step in identifying an abnormal CPK type in muscle tissue, which is a 'final, definitive test in doubtful cases. A warning has been issued to anesthetists and surgeons, through professional publications, that a CPK blood test is mandatory for patients who have suspected familial muscle or nerve disorder, even if the patiënt himself seems to have normal muscle function. The researchers explained that when a patiënt is "put to sleep" by general anesthetic for surgery or childbirth the drug permeates the whole body, and, if there are high levéis of CPK present in muscle and blood tissue, it reacts "in some way yet unknown to produce the fatal high fever. Although the condition has been r a r e 1 y diagnosed or reported its prevalence may be much wider than statistics indicate, they said. Only about 170 deaths from the condition have been reported officially over the past 30 yeafs. However, without any attempt at general screening of thé population, doctors at the U-M, using muscle disorders as a tracer, have located eral families in the Ann Arbor area with members having high blood CPK levéis. Two families tested ■ have more than 30 relatives vsjho possibly could have died had they undergone general anesthesia. Tweive members had already died after surgery, apparently from hyperpyrexia. Based on this, the researchers surmised that an unknown number of hyperpyrexia deaths in the past may have been imstakenly described as "allergie reaction," "postoperative shock" or "complications." Dr. Zsigmond noted that heavy drug and alcohol users may also have high CPK blood levéis so a second test must be used if a false reading is suspected, to postively identify hyperpyrexia susceptíbility. The test is a biopsy which involves removing a small piece of muscle tissue and analyzing it for the presence of "nerve type" CPK which is not present in the muscles of normal persons, even those with high CPK levéis due to other unusual conditions. The second test is usually ordered if the use of local anesthetics is difficult or impractical and the physician wants to be sure it is the qply recourse for s u d p e c te d hyperpyrexia patients. While high temperatura is the main cause of death, the convulsive effect on muscles "almost like strychnine poisoning" is what impressed the U - M researchers and led them to the cause of hyperpyrexia. The tracking down of the fatal enzyme began in 1969 when Dr. Zsigmond asked Dr. Duboff to join in an ongoing search for a preventive. Dr. Duboff, as are other m e m b e r s of the Simpson Memorial Institute, is a specialist in blood disease research. However, he thought the cause of hyperpyrexia might be more related to the body's muscles. He .suggested that the next time a patiënt appeared with any seeming tendency toward hyperpyrexia, they test for blood levéis of enzymes used and thrown off by the muscles. In early 1970, a 36-year-old professional man was examined at Simpson and admitted to University Hospital for a diagnostic surgical procedure. He told surgeons that he had almost died as a youth from a very high fever following surgery. . Dr. Zsigmond and Dr. Duboff conferred and" Dr. ■ Duboff suggested a complete blood enzyme assay. ■ When the results 'carne in, the patient's CPK level was elevated to almost 10 times normal. "We know this must be the ndicator, especially after his ■vife was interviewed and she old us that, of the couple's even children, three had had perations and died," D r . Duboff said. The patiënt underwent surg;ry by nerve block anesthesia vithout complications and a siece of muscle was removed I Dy analysis during the proceiure. A high level of CPK was alo found in the musele and, after further exhaustive biofchemical tests by Starkweathpr, abnormal "nerve type" I CPK also was detected in the I oatient's muscle tissue. Other members of the paient's family were 'called in for blood tests and, of these, more than 20 had elevated PK levéis, the researchers found. Examination also e s t a blished a relationship between [he high blood CPK and musular disorders and this seemd to clinch the enzyme as the causative factor in malignant lyperpyrexia. "However, one thing puzzled us," Dr. Duboff added. The initial patiënt said" he feit fine and there was nothing wrong with his muscles. But upon further examina;ion, his muscles, while large, ivere abnormally weak. His I trength did not come close toj matching his build. He, top it the now familiar pattera o; j yperpyrexia.