In January a column by Jim Spencer of the Denver Post took issue with a common billing modifier for extreme age. “I object to being charged for living to be 73,” stated Spencer’s subject who had anesthesia to repair a fractured arm. With no medical problems and an active life, the patients did not believe that being over 70 was associated with increased work.

Created back at the inception of the Relative Value Guide, the modifier is a chronological surrogate for increased difficulty of anesthesia. At the time, operating on elderly patients was far less common and there were far fewer elderly. Today we operate on many elderly. Many, as in this case, are quite robust with little if any disease load and very active lives. Thus an age greater than 70 does not really provide the anesthesiologist very much information. Although the principal insurer of the elderly, Medicare does not recognize the modifier.

Many old people do well after surgery, but many do not. Whether a patient does well or does poorly is not necessarily related to the procedure undertaken but rather the condition of the patient prior to surgery. Traditional preoperative assessment only partially captures information about fitness and frailty. Because there is no good method to stratify patients by relative fitness or frailty, we may miss opportunities for preventions and rational allocation of services. In the absence of a good method, chronological age and the ASA Physical Status Classifications are used as poor surrogates.

A recent National Institute on Aging/American Geriatrics Society conference was convened last February in Baltimore, Maryland, to discuss the concept of frailty. The conference started off by presenting frailty as a medical/biologic syndrome with a constellation of clinical manifestations. The manifestations we “see” in a frail individual are not necessarily related to disease. The clinical manifestations tend to include sarcopenia (loss of muscle mass), weight loss plus or minus undernutrition, decreased strength and exercise tolerance, slowed motor performance, decreased balance, low physical activity and an increased vulnerability to stressors. The role and/or relationship of cognitive vulnerability to this general syndrome is frequently discussed.

Frailty may be a specific disorder or nonspecific combination of other specific disorders that might occur. Is frailty the same thing as senescence or aging? The underlying physiology is clearly related, so think of the robust 92-year-old who still skis and scuba dives. In the absence of disease, this patient is aging successfully and would not be described as frail. Many younger patients are considerably frailer. The question is how to measure this distinction in a manner that has utility in the perioperative period.

Of the specific disorders at a cellular level that may be associated with frailty are the accumulation of senescent cells and oxidative stress having an impact on mitochondrial metabolism. A concept related to both underlying aging and potentially to frailty is the shortening of telomeres. Critically short telomeres cannot form a protective (capped) structure, leading to cell injury and death. Telomere integrity is related to telomerase activity that is altered with aging.

At a physiologic level, alterations in long-term inflammation (particularly IL-6), changes in sex steroid levels and human growth hormone levels all have an association with frailty. The interaction of sex steroids with cytokine levels may be important. Loss of muscle mass is a common feature in most conceptions of frailty. Sarcopenia has been estimated to cost $18.5 billion in the United States. An underlying mechanism may be an alteration of skeletal muscle mass and quality with accumulating muscle fat associated with decreased muscle strength.

The role of subclinical neurological dysfunction remains highly controversial in aging. Some argue that frailty is primarily a neurologic phenomenon. They cite, for example, postural instability as an example of a variety of systems that are ultimately regulated by the brain. Therefore it is likely to be the brain that is failing when individuals lose stability. Although theoretically appealing, there is much to be done to understand the role of the central nervous system in the development of frailty.

Healthy physiologic functions result from a complex interaction of multiple control systems that enable an organism to adapt to the stresses of everyday life. With aging many physiologic control systems lose complexity, resulting in reduced adaptive capacity or a loss in physiologic reserve. Delving into complex system biology is typically undertaken with a reductionist approach. We pick something, typically a biochemical circulating factor or easily measured physiologic variable, and search for linear changes in mean values. Lewis A. Lipsitz, M.D., Co-Director of the Research and Training Institute of the Hebrew Rehabilitation Center for the Aged in Boston, Massachusetts, has suggested that mathematical models associated with nonlinear systems and chaos theory might be more effective in capturing this loss of complexity in a manner that could be correlated with clinically useful outcomes.

A full systems biological approach also is suggested by Arnold B. Mitnitski, Ph.D., an assistant professor in the Department of Medicine at Dalhousie University, Halifax, Nova Scotia. Dr. Mitnitski has developed a frailty index that is estimated as the accumulation of deficits (symptoms, signs, disease classifications) detected in a given individual. Initially correlated with mortality, it has yet to be tested in a perioperative environment.

Where will we be 10 years from now? A frailty syndrome could be an ICD-x diagnosis. It might be accepted by the Food and Drug Administration as an indication for drugs or interventions, and we may have strategies to prevent frailty. In the more immediate future, we can expect a serious effort to refine our assessment of the elderly in a manner that accurately allows the evaluation and ultimate adoption of improved anesthetic practice.

Jeffrey H. Silverstein, M.D., is Associate Professor for Research,Vice-Chair for Research and Associate Professor of Anesthesiology, Surgery, Geriatrics and Adult Development at Mt. Sinai School of Medicine, New York, New York.