Frailty in Critical Care Medicine: A Review

Abstract

Traditional approaches to clinical risk assessment utilize age as a marker of increased vulnerability to stress. Relatively recent advancements in the study of aging have led to the concept of the frailty syndrome, which represents a multidimensional state of depleted physiologic and psychosocial reserve and clinical vulnerability that is related to but variably present with advancing age. The frailty syndrome is now a well-established clinical entity that serves as both a guide for clinical intervention and a predictor of poor outcomes in the primary and acute care settings. The biological aspects of the syndrome broadly represent a network of interrelated perturbations involving the age-related accumulation of molecular, cellular, and tissue damage that leads to multisystem dysregulation, functional decline, and disproportionately poor response to physiologic stress. Given the complexity of the underlying biologic processes, several well-validated approaches to define frailty clinically have been developed, each with distinct and reasonable considerations. Stemming from this background, the past several years have seen a number of observational studies conducted in intensive care units that have established that the determination of frailty is both feasible and prognostically useful in the critical care setting. Specifically, frailty as determined by several different frailty measurement tools appears associated with mortality, increased health care utilization, and disability, and has the potential to improve risk stratification of intensive care patients. While substantial variability in the implementation of frailty measurement likely limits the generalizability of specific findings, the overall prognostic trends may offer some assistance in guiding management decisions with patients and their families. Although no trials have assessed interventions to improve the outcomes of critically ill older people living with frailty, the particular vulnerability of this population offers a promising target for intervention in the future.

Figure 1.

Conceptual models of frailty. Working definitions of frailty use 3 broad approaches. Each approach has established merit and validated measurement instruments that can be used for their assessment in clinical practice. A, The frailty physical phenotype model evaluates frailty by a set of 5 clinically measurable phenotypic traits that develop as a result of underlying frailty physiology. B, The accumulated deficits model views frailty as a function of a network of a diverse set of age-associated deficits that interact to produce a state of vulnerability. C, The multidimensional model formalizes frailty as a syndrome of multiple interrelated factors, including both biological and nonbiological impairments.

Figure 2.

Mechanisms of frailty. The physiologic underpinnings of frailty are complex and involve a range of interacting elements. A number of physiological perturbations have been noted to be common among frail individuals, but none have specifically been shown to be necessary for the development of frailty. Frailty-related changes occur across multiple biological systems as both an innate element of aging and a response to environmental exposures. These systems interact through a network of interconnected feedback loops to produce the vulnerable state of frailty, including disability, dependence, and adverse health outcomes, particularly following stress. ADL indicates activities of daily living; ADMA, asymmetric dimethylarginine; CRP, C-reactive protein; DHEA, dehydroepiandrosterone; HRQOL, health-related quality of life; IADL, instrumental activities of daily living; IGF1, insulin-like growth factor 1; IL, interleukin; TNFα, tumor necrosis factor α.

Figure 3.

The CFS. The 9-point CFS was adapted from the 7-point scale used in the Canadian Study of Health and Aging. CFS is the most frequently used frailty measurement instrument in the ICU. Categorically, the scale distinguishes among fit (1–3), vulnerable (4), frail (5–8), and terminally ill but not otherwise frail (9) patients. The scale is intended to be self-evident in its application, and notably relies on the characterization of disability in IADLs and ADLs to determine the transition from vulnerability to frailty. ADL indicates activities of daily living; CFS, Clinical Frailty Scale; IADL, instrumental activities of daily living; ICU, intensive care unit. Reprinted with permission from Geriatric Medicine Research, Dalhousie University, Halifax, Nova Scotia.