The U.S. population is rapidly aging. By 2060, 95 million people will be age 65 or older.1 This shift in demographics is closely mirrored in much of the Western world and has major implications for all areas of healthcare delivery, particularly in the perioperative and periprocedural setting where increased age is associated with higher risk of morbidity and mortality. This aging population is expected to increase demand for interventional radiology services, particularly for palliative therapies targeted to elderly patients who are considered high-risk surgical candidates.
Despite the minimally invasive nature of IR, no procedure is without risk and a minority of our patients do experience complications, longer-than-anticipated recovery and rehabilitation, and even decreased health and death. With an increasing number of geriatric patients seeking IR services, identification of patients at higher risk for complications will allow for improved pre-procedural counseling and patient selection, as well as targeted application of resources to improve the perioperative risk profile for select patients.
Pathophysiology of frailty
Emerging data indicate that that immune and endocrine dysfunction along with malnutrition shape the stigmata of frailty. Frail patients have altered distribution of cytokines with higher proinflammatory markers, decreased sex hormones, higher levels of cortisol and vitamin D deficiency. Together, these factors result in sarcopenia, anemia, insulin resistance, decline in anabolic metabolism and leukocyte function, which all impact the patient’s risk of infection and healing abilities after surgery. Decreased muscle mass and increased adipose tissue that characterize frail body habitus alters drug metabolism, leading to higher duration of action of lipophilic drugs and higher peak plasma concentration of hydrophilic drugs. This impact, along with renal and hepatic impairments that accompany aging, results in increased risk of drug toxicity in the setting of anesthesia and chemotherapy.2–3
Measuring frailty
Frailty is defined as a multidimensional syndrome associated with aging that includes decreased physiological abilities and increased vulnerability to stressors.
There are two widely accepted approaches to conceptualizing and measuring frailty: The frailty phenotype and the deficit-accumulation frailty index (FI).4–5
In the phenotypic model described by Fried et al,6 derived from the Cardiovascular Health Study (CHS), the presence of frailty is determined on the basis of five physical indictors:
- Unintentional weight loss
- Exhaustion
- Weakness
- Slow walking
- Low physical activity
Variations of this model have been developed in specific patient populations. For example, the performance-based Liver Frailty Index (LFI), which measures grip strength, chair standing and balance testing, was specifically developed to assess frailty in cirrhotic patients.7 Among transplant candidates, frailty as measured by the LFI has demonstrated to be more predictive of waitlist mortality than the Model of End-stage Liver Disease (MELDNa) alone and more predictive of poor health and higher risk of acute cellular rejection post–liver transplantation.6–7
The FI model developed by Rockwood et al in the Canadian Study of Health and Aging (CSHA) conceptualizes frailty as a cumulative measure of medical, social and functional deficits over time.8 The original frailty index included 70 individual variables, with subsequently validated modified frailty indices (mFI) mapping the original frailty index to 11 and then five variables including8:
- Congestive heart failure
- Diabetes mellitus
- Chronic obstructive pulmonary disease or pneumonia
- Partially dependent or totally dependent functional health status
- Hypertension requiring medication
These patient-specific factors are documented in the National Surgical Quality Improvement Program (NSQIP) database, allowing for large-scale retrospective studies across surgical disciplines to assess the impact of frailty as captured by the mFI on postoperative outcomes. Unfortunately, the absence of a high-quality data registry in IR that includes validated frailty metrics poses a significant barrier to frailty research in our specialty.
Frailty and healthcare outcomes
Over the past decade, frailty has emerged as a clinically salient entity for predicting general adverse health outcomes in the geriatric population. In many studies, frailty is found to be independently predictive of incidental falls, functional disability, hospitalization, morbidity and mortality.9 In the surgical realm, pre-operative frailty has proven to be a robust metric for predicting adverse surgical outcomes such as postoperative infection, prolonged hospitalization, discharge to skilled nursing facility and mortality. Across surgical specialties, frailty assessment routinely outperformed many of the conventional surgical risk stratification tools such as American Society of Anesthesiologists (ASA) classification, Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score and Eastern Cooperative Oncology Group (ECOG) performance status. Frailty has been demonstrated to be predictive of adverse outcomes in endovascular interventions in the fields of cardiology and vascular surgery, and predictive of surgical complications, radiation and chemotherapy intolerance and disease progression in cancer patients.10–13 While these specialties share surgical techniques similar to those of IR and have overlapping patient population, data on the prevalence of frailty among IR patients and its impact on postprocedural outcomes is currently lacking.
Frailty and IR
While an interventional radiology procedure such as transarterial chemoembolization is seen as a minimally invasive, low-risk oncological therapy, it still poses a myriad of physiological challenges for patients. The procedure itself delivers chemotherapy agents to the liver, which carries a higher likelihood of toxicity in frail patients with altered metabolism. Patients undergo periprocedural fasting, opioid analgesics and anesthetic agent. They experience postprocedural pain, nausea and vomiting, an unfamiliar hospital environment and a period of immobility. Although these series of minor insults may be inconsequential for a healthy patient with sufficient physiological reserve, they can result in higher risk of short-term complications and long-term mortality in frail patients, as we have observed from our own institutional analysis.14
Conclusion
Frailty is emerging as an important determinant of healthcare and surgical outcomes in the elderly population and is increasingly being considered to guide treatment decisions across medical and surgical specialties. Routine assessment and documentation of frailty in IR has significant potential to improve patient outcomes in our specialty. For example, frailty assessment prior to IO procedures can guide appropriate dosage and selectivity in transarterial chemotherapy and radiotherapy, potentially limiting risk of toxicity in high-risk patients. It can also guide the choice of antibiotic prophylaxis to decrease risk of postoperative infection and anesthetic techniques such as the use of neuraxial blockades to reduce opioid consumption. Frailty can guide selective use of specialized hospital resources such as involvement of palliative care and admission to the Acute Care for Elders (ACE) unit for observation, as well as early involvement of nutrition counseling and physical therapy for pre-procedural optimization.
Ultimately, as interventional radiologists, it is up to us to uncover the interplay between frailty and IR procedural outcomes and to incorporate this knowledge into our clinical practice to better serve the growing geriatric patient population.
References
- Mather M, Jacobsen L, Pollard K. Aging in the United States. Population Bulletin 70, no. 2 (2015).
- Lin HS, McBride RL, Hubbard RE. Frailty and anesthesia—risks during and post-surgery. Local Reg Anesth. 2018;11:61–73.
- Amrock LG, Deiner S. Perioperative frailty. Int Anesthesiol Clin. 2014;52(4):26–41.
- Ethun CG, Bilen MA, Jani AB, Maithel SK, Ogan K, Master VA. Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology. CA Cancer J Clin. 2017 Sep;67(5):362–377.
- Czobor NR, Lehot JJ, Holndonner-Kirst E, Tully PJ, Gal J, Szekely A. Frailty in patients undergoing vascular surgery: A narrative review of current evidence. Ther Clin Risk Manag. 2019;15:1217–1232.
- Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research Group. J Gerontol A Biol Sci Med Sci. 2001 Mar; 56(3):M146–56.
- Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489–95.
- Lai JC, Covinsky KE, Dodge JL, Boscardin WJ, Segev DL, Roberts JP, Feng S. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology. 2017 Aug;66(2):564–574.
- Xue QL. The frailty syndrome: Definition and natural history. Clin Geriatr Med. 2011;27(1):1–15.
- McIsaac DI, MacDonald DB, Aucoin SD. Frailty for perioperative clinicians: A Narrative review. Anesth Analg. 2020 Jun;130(6):1450-1460.
- Ko FC. Preoperative frailty evaluation: A promising risk-stratification tool in older adults undergoing general surgery. Clin Ther. 2019;41(3):387–399.
- Fozouni L, Mohamad Y, Lebsack A, Freise C, Stock P, Lai JC. Frailty is associated with increased rates of acute cellular rejection within 3 months after liver transplantation. Liver Transpl. 2020 Mar;26(3):390–396.
- Subramaniam S, Aalberg JJ, Soriano RP, Divino CM. The 5-Factor Modified Frailty Index in the geriatric surgical population. Am Surg. 2020 Dec. doi: 10.1177/0003134820952438.
- Rabei R, Vakil P, True-Yasaki A, Phuong J, Kohi M, Lokken R, Lehrman E, Kolli K, Kohlbrenner R, Fidelman N. Abstract No. 391 Frailty is predictive of complications after transarterial chemoembolization. JVIR. 2020 Mar;31(3):S176.