The Frailty Syndrome: Anesthesiologists Must Understand More and Fear Less

Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less. —Marie Skłodowska Curie1 As of 2019, there are approximately 703 million people worldwide who are ≥65 years of age, and recent data suggest that by the middle of the current century, this number will approach 1.5 billion.2 In 2019, the National Academy of Medicine (NAM) announced its Healthy Longevity Global Grand Challenge.3 This initiative is designed to identify innovative approaches to improve healthy aging and attain the formidable, yet commendable, goal of increasing disease-free healthy longevity, a concept recently coined “immorbidity” by the Dutch scientist Jaap Goudsmit.4 An entire medical subspecialty has grown out of this concept; the principal expertise of geriatricians is in the active promotion of healthy aging.5 As experts in perioperative medicine, the time has similarly come for anesthesiologists to play a more active role in supporting the healthy aging of older adults who require some form of anesthesia care. An initial step toward improving the perioperative care of older adults requires a better appreciation of how clinical outcomes are impacted by frailty. Frailty is a multidimensional syndrome characterized by increased clinical vulnerability linked to diminished physiological reserve and decreased resistance to stressors.6,7 Although not solely associated with advanced age, a recent systematic review and meta-analysis reported that the prevalence of frailty in a general surgical population 61–77 years old ranged from 10.4% to 37%, and frailty was associated with an 8-fold increase in 30-day mortality.8 Despite a significant increase in scientific knowledge related to frailty since Fried et al6 described the syndrome as an operational phenotype in 2001, this state of increased vulnerability remains a major impediment to attaining this goal of disease-free healthy longevity. Given the expected increase in older adults requiring anesthesia care, it is imperative that anesthesiologists better appreciate the immediate perioperative and longer-term consequences of frailty. The fundamental goal of this month’s frailty-themed issue of Anesthesia& Analgesia is to essentially put this syndrome “on the radar” of anesthesiologists and perioperative physicians. In doing so, anesthesiologists will be better prepared to care for this increasing vulnerable patient population. Such an educational endeavor is especially timely given the recent introduction of the American College of Surgeons Geriatric Surgery Verification Program,9 which recommended that geriatric surgical patients be screened for the major components of frailty as part of their preoperative evaluation. Much more research still needs to be done to determine how to better improve clinical outcomes in frail older adults. A considerable number of unknowns regarding the true significance of this syndrome remain, especially in terms of reversibility of this state. Nevertheless, this themed issue highlights areas where there is reasonable scientific evidence to (1) improve the preoperative identification of frail (and “prefrail”) patients; (2) better understand the indications for perioperative geriatric consultation; (3) develop evidence-based perioperative care plans better designed to measure and improve clinical outcomes; (4) better approach informed consent and shared decision-making discussions whenever possible; and (5) better integrate palliative care in this vulnerable patient population. We have taken a multidisciplinary educational approach. Thus, this issue includes articles authored by anesthesiologists, geriatricians, intensivists, and palliative care specialists. These experts are at the forefront of frailty research, especially as it relates to the practice of anesthesiology and perioperative medicine. Another objective of this themed issue is to identify and highlight knowledge gaps in our understanding of how frailty mechanistically impacts risk, perioperative care, and clinical outcomes. Wherever applicable, the authors have identified scientific knowledge gaps where additional frailty-focused research is warranted. By singling out these knowledge gaps, we hope that this will help inform innovative directions in frailty research. Perhaps, the identification of these unanswered scientific questions will also serve as impetus for more anesthesiologists to pursue frailty-focused research. For readers wishing to gain an increased appreciation of frailty, as it specifically relates to clinical anesthesiology, McIsaac et al10 have written an excellent narrative review specifically nuanced for perioperative physicians. These authors clarify what frailty is and, importantly, what does not constitute frailty—especially how it differs from comorbidity and multimorbidity. In addition, this manuscript reviews the 2 common approaches to conceptualizing frailty: the frailty phenotype6 and the cumulative deficit model approach.7 Finally, this work provides an important overview of how frailty negatively impacts a myriad of common postoperative outcomes in older adults. Although a common myth exists that clinicians can often recognize frailty using a “know it when I see it” approach, a concept in the spirit of late US Supreme Court Justice Potter Stewart’s aphoristic opinion on obscenity,11 the literature does not support such a notion.12 Hence, formal frailty assessments are recommended in the preoperative period and are important for more accurately predicting risk. However, with over 70 frailty screening instruments available, which approach should perioperative physicians choose? The review by McIsaac et al10 and the review by Nidadavolu et al13 comprehensively examine how frailty can be effectively assessed perioperatively, while taking into consideration many of the logistical obstacles in the clinical environment. Nidadavolu et al13 also provide a thorough overview of common health care outcomes that are negatively impacted by frailty, again underscoring the need for anesthesiologists to become more proactive in developing and investigating anesthetic approaches that mitigate risk in these patients. The granular information that both of these reviews provide on frailty assessment approaches is of tremendous value for anesthesiologists planning to incorporate frailty screening protocols for older adults in a preoperative evaluation clinic setting. Furthermore, given that the addition of a frailty assessment may improve existing comorbidity-based risk prediction systems, the need to become more familiar with these frailty assessment approaches cannot be overemphasized, especially as they may be tied ultimately to health care reimbursement.14 In an intensive care unit (ICU) setting, frailty is quite common with a reported prevalence of 30% in a population of >18 years of age.15 In octogenarians, this number increases to as high as 43%.16 In their review, De Biasio et al17 describe common approaches to and challenges associated with evaluating frailty in an ICU setting. Furthermore, they effectively discuss how frail patients commonly present to the ICU and their clinical trajectories beyond that of mortality. Common interventions, such as increased mobility and nutritional approaches, that are being currently implemented to mitigate the detrimental consequences of ICU frailty are also discussed. However, the authors correctly conclude that more studies are needed to specifically assess whether such interventions actually improve outcomes in this ICU population. Complementing the work by De Biasio et al17 is a narrative review by Paul et al18 focusing on novel translational mechanisms and potential therapeutic targets of frailty in critically ill older adults. Paul et al18 summarize many of the putative mechanisms thought to underlie the frailty of critical illness including inflammation and its failed resolution, mitochondrial myopathy, and neuroendocrine abnormalities. Again, both of these reviews effectively identify translational research knowledge gaps, including potential therapeutic interventions, that need to be further investigated to perhaps improve the care of critically ill patients with frailty. Although frailty has been associated with a high degree of morbidity and mortality, much of this research has been performed by geriatricians, surgeons, and internists who are not primarily involved in the practice of perioperative medicine let alone anesthesiology. Therefore, given our specialty’s charge to advance safe, expert perioperative care, anesthesiologists need to play a more active role in pursuing frailty-focused research. This is necessary to answer questions that are highly relevant to the practice of anesthesiology, pain management, and critical care medicine. Thus, in this issue, we have included several articles from anesthesiology-focused research groups. These anesthesiologists are at the vanguard of frailty research, and their scientific investigations are highly relevant to perioperative anesthetic management as well as the informed consent and shared decision processes. The original research articles by Poulton et al,19 Mahanna-Gabrielli et al,20 and Nakano et al21 highlight patient-focused postoperative outcomes in frail surgical patients: disposition after multisystem trauma, cognitive sequelae, and longer-term functional outcomes. Poulton et al19 using a sophisticated meta-analytic approach incorporating 16 studies and 5198 patients observed that frailty after multisystem trauma was associated with significantly increased mortality, significant organ-based complications, and adverse hospital discharge disposition. Although previous work has demonstrated that the preoperative frailty in cardiac surgical patients was associated with at least a 2.1-fold increase in the relative risk of postoperative delirium22 (POD), questions remain as to whether this effect persists in a noncardiac surgical population. The research article by Mahanna-Gabrielli et al20 examines this cognitive outcome in older adults undergoing major noncardiac surgery and observed that an increased risk of POD is not only observed in frail patients but also in prefrail patients. Finally, Nakano et al21 observed a decline in Instrumental Activities of Daily Living (iADLs) in frail patients 1 month after cardiac surgery. Interestingly, delirium was particularly associated with increased vulnerability to functional decline. Recently, there have been increasing calls for health care providers to incorporate palliative care within the care plans of all seriously ill patients, including older adults with the highest degrees of frailty. Crooms and Gelfman23 expertly discuss the main domains of palliative care, the control of symptoms, and palliative care goals as they related to patients living with frailty. These authors also provide important information, nuanced for anesthesia care providers, on how to better integrate palliative care within the perioperative care goals of frail patients. Because patients living with frailty are at increased risk for a cascade of detrimental postoperative outcomes, the issue of informed consent is critically important in this context. Therefore, this thematic issue includes a special article authored by Silbert and Scott24 who make a logical argument that labeling patients as “frail” could essentially have a Janus effect—a 2-faced impact with both positive and negative implications. On one hand labeling patients as “frail” or even “prefrail” could benefit patients by identifying them as being at increased risk for perioperative morbidity and mortality. However, this identification could come at the expense of increased risk of ageism and medical paternalism. In turn, both of these practices could negatively impact patient care by interfering with the informed consent and shared decision-making processes. Silbert and Scott24 summarize the key elements of appropriately obtained informed consent as well as the logistical and ethical challenges to proper informed consent procedures in patients living with frailty. Moreover, because these authors accurately point out, frail patients are likely at particular risk of perioperative neurocognitive disorders (postoperative cognitive dysfunction and POD); therefore, the default practice should be that this risk be openly disclosed. Unfortunately, this disclosure is often not regularly performed during the informed consent process, especially in frail patients. Prehabilitation is being increasingly used in an attempt to decrease risk by improving a patient’s functional reserve before a major stressor such as surgery. However, many questions remain regarding the effectiveness of these programs, particularly in frail patients. Norris and Close25 specifically review various modalities of prehabilitation as they are applied to frail populations. They also discuss how they differ from enhanced recovery after surgery (ERAS) protocols, although there is often overlap between the 2 approaches. The evidence for pursuing prehabilitation in frail patients is also discussed, and it is quite apparent that additional research in this field is warranted. Finally, the importance of multidisciplinary collaboration with geriatricians and the importance of the comprehensive geriatric assessment in the care of the frail surgical patients are also reviewed. Overall, Norris and Close25 provide very useful guidance for those clinicians planning to establish prehabilitation programs for patients with or at risk for frailty. In summary, in the spirit of the aforementioned quote by Madame Curie, anesthesiologists should strive to better understand frailty and its clinical and psychosocial consequences, so they do not fear. As the demographic transition toward older adults continues, healthy longevity should indeed remain a health care goal of paramount importance. Therefore, anesthesiologists and perioperative physicians must do their part to better appreciate this state of increased clinical vulnerability so that they can do more and fear less when rendering clinical care to patients living with frailty. Whether in academic or community practice, anesthesiologists have always played a critical, yet often underrecognized, role in improving modern health care. We hope that this themed issue will inspire physicians in our specialty who care for older adults to “answer the call” once again. That call is to better understand frailty, attempt to mitigate its detrimental effects, and certainly not to fear. DISCLOSURES Name: Elizabeth L. Whitlock, MD, MSc. Contribution: This author helped conceive and cowrite the manuscript. Name: Robert A. Whittington, MD. Contribution: This author helped conceive and cowrite the manuscript. This manuscript was handled by: Jean-Francois Pittet, MD.