FrailtyLyndon Woytuck

What is frailty?

An age-related clinical state of increased vulnerability and decreased ability to maintain homeostasis

Centrally characterized by declines in functional reserves across multiple physiologic systems

Related to, but distinct from, disability and disease states Decline in independence and functional capacity with energy loss,

vigour and/or weight loss Not an inevitable consequence of aging It is at the core of Geriatric Medicine; Geriatrics is particularly skilled in

care of frail elderly

Frailty

Because of the high-risk status of frail older adults, geriatric medicine seeks to intervene in frail patients to prevent or minimize illness and dependency.

Those in the “fourth age” after 85 years (in developed countries), are particularly biologically vulnerable and frail and have compromised ability to tolerate stressors.

In frailty, well-being becomes increasingly dependent on the use of extrinsic compensations to maintain life and autonomy, because there is diminished ability to compensate physiologically.

Aging is associated with increased likelihood of frailty Older persons have reduced physiological reserve than younger persons These changes are likely independent of disease In old age, disrupted homeostasis can more easily result from a combination of multiple

processes (both greater insults and poor compensatory mechanisms) This is opposed to disease which is a rare occurrence and has a discrete syndromic entity

Why is frailty important?

Frail older persons are at risk for multiple adverse health outcomes, including Medical instability, Disability and dependency, Institutionalization, Injuries, Falls, Acute

illness, Hospitalization, Health care resources utilization, Slow or incomplete recovery from illness and/or hospitalization, High risk of iatrogenesis and side effects from medical interventions, and Mortality

They have compromised ability to tolerate hospitalization or invasive procedures and are at high risk of related complications

They are in high need of health care and community and informal support services, as well as long-term care

The most powerful predictors of longevity and functional outcomes are measures of subclinical organ system changes, physical, functional, and cognitive variables to explain the increased variation in health status, outcomes, or response to therapy NOT presence or absence of disease, or disease activity alone

Epidemiology

Estimates ranging from 10% to 25% of persons aged 65 years and older, with as many as 30% to 45% of those aged 85 years and older identified as frail.

Not explained by disease alone The prevalence of frailty increases dramatically with age Continuum of frailty among older adults underlies some of the heterogeneity of

health status observed with increasing age thought clinically to be a distinct causal pathway to disability, with frailty being a

major aetiologic risk factor independent of disease frailty is thought distinguishable from disability (as an outcome) and

comorbidity, although there are overlapping co-prevalences increased susceptibility to multiple chronic diseases not explained by “classic”

risk factors.

How are disability and frailty related?

Pathophysiology

In aging individuals, the variability in health and functional status is explained less and less by the effect of clinically evident or even subclinical diseases. Older age is associated with increased vulnerability to multiple diseases with no evident pathogenetic connections. Such global vulnerability is not explained by changes in recognizable risk factors.

Increased risk of adverse outcomes associated with frailty is a result of an increased vulnerability to stressors itself caused by a decreased ability to maintain homeostasis when the individual is stressed.

Stressors can be intrinsic, such as infection, or extrinsic, such as change in environment. In addition to the clinically frail, a subset of older individuals have subclinical frailty

have increased vulnerability to adverse outcomes in response to stressors, but without the clinical stigmata of frailty or any of its outcomes

Frailty results from underlying physiologic and/or biologic alterations that are age-associated and maybe compounded by single or multiple diseases, or may even be an end-stage outcome of severe disease.

Key systems: musculoskeletal, hormonal, immune, and inflammatory systems, with likely contributions from the autonomic and central nervous systemsmalnutrition,

Includes functional impairment, cognitive impairment and depression

Pathophysiology Age-related frailty may explain why older age is associated with the

increased variability in response to treatments, both in terms of effectiveness and risk of side effects, not explained fully by disease status.

The increased risk of iatrogenesis is likely a product of the altered reserves and associated physiologic vulnerabilities that are components of frailty.

Dysregulation of homeostatic or communications systems at the molecular and physiological level declines in hormones important in muscle mass maintenance such as IGF-1

and DHEA-S, and increases in afternoon cortisol levels and in inflammatory and clotting markers, point toward the immune and neuroendocrine systems as likely candidates as the physiological source of this dysregulation.

increased oxidative stress generated in mitochondria is likely to set in motion many processes that can impair physiology (molecular basic aging)

declines in energy production (ATP) can lead to less efficient signal transduction and protein transcription and translation in many cells, which in time leads to alterations in biological systems.

free radicals damage mitochondrial DNA, which leads to less efficient energy production and greater increases in oxidative stress. This process may lead to increasing DNA and protein damage, as well as direct transcription of inflammatory mediators, which are strongly associated with frailty

Clinical characteristics

composite image of loss of muscle mass (sarcopenia), weakness, slowed pace of movement, decreased activity and engagement, and possibly unexplained weight loss—often in combination.

Frailty is manifested as an impaired ability to cope with challenges in health and reduced ability to regain a stable health status, possibly related to reduced functional reserve. Severity of frailty spans from subclinical to a clinical stage to impending death.

aggregate dysregulation of many systems that results in the vulnerability and clinical presentation of frailty more than the dysregulation of any one system.

Continuum of resilience/frailty

Robu

stResilient; Recovers readily from stressors

Subc

linica

lly fr

ailAppears

resilient, but recovers slowly or incompletely from stressors & may manifest adverse consequences Ea

rly Fr

ailtyClinical

appearance of being frailPoor tolerance of stressors; no disability La

te Fr

ailtyClinical

appearance of being frailPoor tolerance of stressors very slow recoveryOutcomes: disability due to decreased energy, strength En

dsta

ge Fr

ailtyClinical

appearance of severe frailty; low LDL, cholesterol, strength; weight lossOutcomes: dependent; high risk of death within 12 months

The Vicious Cycle of Frailty

Diagnosis

Frailty is a condition of impending deterioration in health and functional status that requires immediate attention to prevent disability and other associated outcomes.

No formally agreed-upon diagnostic criteria identify the biological state of vulnerability underlying frailty, or clinically evident frailty.

Recognition of standardized clinical approaches is a critical next step to improve screening and targeting of care and implementation of effective interventions to decrease premature or preventable frailty and decrease adverse outcomes associated with frailty

There exists a subset of older adults with advanced frailty stigmata and significant outcomes, particularly disability or dependency, who have lost reserves and resilience with a very high likelihood of dying within 6 - 12 months, and quite unlikely to respond to therapies

CHS frailty phenotype

a clinical presentation that appears to be the outcome of multiple changes and constitutes a constellation of interrelated presentations and likely involved in a vicious cycle of dysregulated energetics

Treatment and prevention Identify vulnerable, frail individuals before the adverse outcomes for which they are at risk

occur Identification of secondary frailty resulting from latent, undertreated, or end-stage disease

such as congestive heart failure, which could be causing a catabolic state and weight loss or decreased nutritional intake, which are responsive to therapy including congestive heart failure, diabetes, thyroid disease, tuberculosis, and other chronic

infections, undiagnosed cancer, and inflammatory conditions such as temporal arteritis. Psychological conditions such as depression, psychosis, and grief—as well as dementia

Prevention of related adverse outcomes: falls, delirium, and disability and modify vulnerability (medications, hospitalization, surgery, or other stressors)

Outpatient geriatric assessment and intervention, with patient-centered goal-setting, family and/or caregiver involvement, and regular follow-up by a geriatric MDT. longitudinal, continuous care slows functional decline, reduces symptoms and adverse outcomes in

frail older adults If frailty is the primary condition, a goal should be to institute supportive interventions early.

target the environmental triggers, especially low activity, inadequate nutrition, and catabolic medications.

prevention of muscle loss and improvement in strength and energy; maintaining strength and nutritional intake

Management

Prevention in old age may need to be focused on reinforcing homeostatic mechanisms rather on risk factors for specific diseases.

The acute care approach is counter-intuitive in terms of frail individuals Change in nutrition and exercise are the only interventions that have been shown to prevent

disability. Frail older persons require intensive and multidimensional continuous care and have high need of

community and informal support services. These care needs necessitate a shift in the deployment of heath care resources

Frailty and the elderly must be considered in the appropriate clinical setting in order to deliver appropriate care tailored to the patient

Development of comprehensive geriatric assessment and creation of specific geriatric systems for care delivery as optimal clinical approaches to decreasing preventable adverse outcomes in public health

Inappropriate care of frail individuals in an unsuited system can lead to higher costs and poor patient outcomes

Case 1

The first case involves a very robust older man who underwent surgery and did very well. He was 75 years old, had a history of hypertension, mild congestive heart failure, and chronic knee osteoarthritis. He walked daily and lifted some weights, but had experienced increasing knee pain that slowed his activity level. He was admitted for an elective knee replacement and did very well in the postoperative period.He went home after 3 days on anticoagulation and narcotic pain medications, tolerated home physical therapy for 2 weeks, and returned close to his functional baseline within a month.

Case 2

In the second case, a man with a similar clinical history exhibited vulnerabilities to adverse outcomes following surgery that differentiated him from the first patient. This man, also 75 years old and with a history of hypertension, mild congestive heart failure, and chronic knee osteoarthritis, walked several times a week for exercise and volunteered at a hospital gift shop. He had to stop these activities because of increasing knee pain and fatigue about 2 months prior to surgery. He underwent elective knee replacement and did well in the immediate postoperative period. However, after being given narcotic pain medications, he became delirious, pulled out his foley catheter, and fell out of bed. He refused all physical therapy interventions and developed incontinence. He was eventually transferred to a subacute rehabilitation facility, where he gradually recovered over 3 weeks. He was then transferred to home and required 3 more weeks of physical therapy. After 3 months, he approached his previous functional baseline, but still described fatigue and inability to do as much as he did before.

Case 3

An obviously frail, vulnerable older man without known medical illness had a series of adverse events near the end of life.

He was 83 years old and had lived alone since his wife died 5 years earlier. He had a history of hypertension, compensated congestive heart failure, and a fall with fracture of left hip 3 years earlier. He did most of his own activities of daily living, but was not able to get out in the community anymore because of fatigue and fear of falling. He had minimal activity and almost no planned exercise.

He was found on the floor by a neighbor when it was noticed that he had not been outdoors to get his morning newspaper. The patient reported that he had simply fallen and was too weak to get up.

In the emergency room and subsequent hospitalization, the physicians identified diffuse muscular weakness and elicited a history of a 10 pound weight loss over a year, but found no other laboratory or obvious medical etiology for his decline and weakness. The patient was transferred to subacute rehabilitation and gradually improved to the point where he could ambulate 20 feet with a walker. However, he was not able to care for himself as he did previously, and was therefore transferred to an assisted living facility. He died there, of undefined causes, 3 months later.

References

Hazzard's Geriatric Medicine & Gerontology, Sixth Edition Linda P. Fried ■ Jeremy D. Walston ■ Luigi Ferrucci Chapter 52: Frailty

Toronto Notes 2015, 31st edition. Hall and Premji et al.