Effects of Patient Age on Muscle Relaxant

HE AGING process has a profound effect on the actions of many drugs including the nondepolarizing muscle relaxants. This fact has long been appreciated by anesthesiologists. As early as 1957, Foldes stated that "adequate operating conditions in the elderly can be achieved with smaller milligrams per kilogram doses of relaxants than in young adults of corresponding weight."l He further recommended that the initial dose of the relaxant should be reduced by two thirds to one half of the usual adult dose. Although Foldes' clinical observations concerning the use of relaxants in the elderly were widely accepted, there were no careful clinical studies to support these observations. The lack of such studies was appreciated. Bender, in a 1964 review of the pharmacological effects of aging on drug activity, stated that one of the most important reasons for writing the review was "an attempt to stimulate further interest in the study of the role of aging [on drug activity]--and to stress the lack of studies in man. ''z A breakthrough came in the 1970s with the development of numerous analytical methods to accurately measure concentration of the relaxants in man. There followed an efflorescence of studies on the distribution, elimination, and actions of muscle relaxants in man. Once pharmacokinetic and pharmacodynamic values had been established for the normal human, investigators' attention was directed to studies of both pathological and physical states, in which the pharmacokinetics and pharmacodynamics of muscle relaxants might vary from the normal state. The effects of increasing age on the pharmacology of muscle relaxants attracted wide attention for several reasons. First, a number of review articles were published focusing on alteration in body composition and function with age and their possible effect on drug therapy in the elderly. 3-8 Secondly, we are an aging population. This is especially appreciated by one of the authors (RSM) of this review, who will soon become a senior citizen. At the present time, approximately 12% of the United States population is over the age of 65, and one third of all hospital beds in this country are occupied by the elderly. The elderly have become such a large segment of our population that gerontologists have subdivided the elderly (persons over age 65) into subgroups. One of the subgroups, the very elderly (over age 85), is in fact the fastest growing segment of our population. The changes are reflected in the type of patients we as anesthesiologists see in our practice. In our own clinic, Columbia Presbyterian Medical Center, a decade ago, 15% of patients undergoing anesthesia were age 70 or older. Today this figure approaches 20%. This review examines the pathophysiological changes that normally accompany advancing age (Table 1), and then examine how these changes affect the distribution, elimination (pharmacokinetics), and actions (pharmacodynamics) of the nondepolarizing muscle relaxants. DISTRIBUTION Two changes that may have a profound effect on drug distribution are the decrease in lean body mass (20% to 25%) and the increase in body fat (50% to 75%) seen with advancing years. 9'~~ There is a sex difference between these two tissues in that women have more fat and less lean body mass than men at any age, but the trend toward an increase in body fat with aging is the same in both sexes. These changes could cause a decrease in the distribution of water-soluble drugs (such as the muscle relaxants) and an increase in the distribution of fat-soluble drugs. Total body water has also been shown to increase significantly with age TM (up to 15%). This is accompanied by a decrease in cell mass. 9 Ritschel 4 has pointed out