Advances in Anesthesia 32 (2014) 119–131

ADVANCES IN ANESTHESIA

Perioperative FrailtyDefinitions, Evaluation, Implications for

Management, Impact on Outcomes After Anesthesia

Sheila Ryan Barnett, MDDepartment of Anesthesiology, Beth Israel Deaconess of Medical Center, Harvard Medical School,330 Brookline Avenue, Boston, MA 02215, USA

Keywords

� Frailty � Perioperative � Anesthesia � Outcomes

Key points

� Frailty is an important syndrome in the geriatric population.� The occurrence of frailty has important prognostic implications, for patients ingeneral and in particular at the time of surgery.

� Anesthesiologists should be able to recognize and diagnose frailty in older pa-tients and understand the implications for outcomes.

� Measuring frailty may contribute to decision-making capability for patients andtheir families, as well as anesthesiologists and surgeons.

� Future research should be directed toward strategies to reverse frailty and reduce

INTRODUCTIONAdvanced age is not considered a contraindication to surgery, and the elderlyrepresent a significant proportion of the patients undergoing surgical and inva-sive procedures. In the United States more than 40% of surgery is performed inpatients more than 65 years of age. As the volume of geriatric patients con-tinues to grow, so does the understanding that older patients represent a specialpopulation for anesthesiologists, carrying inherently high risks from complica-tions and even mortality. A major challenge encountered when caring for olderpatients is evaluating physiologic versus chronologic age, and estimating theconsequences of aging and morbidity on a patient’s functional reserve. It hasrecently been recognized that frailty is an important and increasingly commoncondition in the geriatric population that predisposes patients to adverse out-comes following anesthesia and surgery [1–6].

complications and readmissions in frail patients undergoing surgery.

E-mail address: sbarnett@bidmc.harvard.edu

0737-6146/14/$ – see front matterhttp://dx.doi.org/10.1016/j.aan.2014.08.012 � 2014 Elsevier Inc. All rights reserved.

120 BARNETT

WHY STUDY FRAILTY?It is well known that, as people age, organ function declines and patients’reserve functions are diminished. In addition, common comorbidities such ashypertension, diabetes, coronary disease, and pulmonary disease are allmore common in older patients and further reduce an elderly person’s reservefunction. However, the impact of aging or age-related diseases can vary consid-erably and the older population is by nature heterogeneous. Frailty is now awell-accepted concept that seems to provide a global assessment of the com-bined impact of aging and comorbidity on reserve function.

The preoperative identification of frailty ideally leads to strategies to reversethe frailty or improve baseline functional reserve [7–9]. Although the timeavailable before surgery may often preclude the implementation of any pre-emptive measures, there may be circumstances in which early identificationof frailty could affect decision making or lead to strategies to improve out-comes. It is known that exercise programs in very old patients may lead to im-provements in several domains including strength, cognitive well-being, andbalance. Physical activity programs may also lead to reduction in inflammatoryactivation, production of free radical scavengers, metabolic modulation, andimprovement of insulin resistance [10]. Both muscle weakness and poor nutri-tion are hallmarks of frailty and low albumin has been associated with negativeperioperative outcomes [11–14]. However, the data on preoperative nutritionin frail patients are still insufficient, likely in part because of the often limitedperiod of time available before scheduled surgery in frail patients.

DEFINING FRAILTYFrailty is a state of reduced physiologic reserve and consequent increasedvulnerability from challenges that threaten homeostatic balance [11,12,15].Frailty is not a disease state in and of itself, but instead represents a constella-tion of symptoms or conditions that lead to a recognizable decline in physicaland cognitive function and general endurance [1,2,14,16]. Frailty is associatedwith an increased risk of adverse events such as falls, delirium and generalmorbidity. In the surgical domain, frailty has been increasingly recognized asan important geriatric syndrome that is associated with increased risk of com-plications, length of stay, discharge disposition and mortality [8,16–19].

The prevalence of frailty is not fully known, but for community-dwelling el-ders it is estimated at 3%–7% for 65–75 years, 20%–26% for 80–90 years andaround 33% for people more than 90 years [20,21]. Frailty is especially preva-lent in patients with cardiovascular disease, and the presence of frailty isbecoming recognized as an important variable when considering appropriatetreatment strategies for cardiovascular patients [22–25].

PATHOPHYSIOLOGYThe causes leading to the development of frailty are not fully understood.During ‘normal’ aging, gradual cell and molecular damage occur through mul-tiple mechanisms. At some point the overall effect/affect of age-related damage

121PERIOPERATIVE FRAILTY

is enough to negatively influence organ function, ultimately reducing reservefunction in the older patient. In frail patients the rate and extent of decline isaccelerated and the accumulation of deficits in multiple organs systems leadmore rapidly to a global decline in function [11,15,26,27]. There is increasingevidence that the pathophysiology of frailty involves an interconnection be-tween inflammatory changes and alterations in endocrine and immune modu-lation [28]. Inflammatory markers such as C-reactive protein and interleukin-6(IL6), and immune alterations characterized by higher neutrophil and mono-cyte cell counts, have been found in frail elderly populations. Endocrineabnormalities, including insulin resistance, and declines in IGF-1 and testos-terone have also been identified in frail populations [29]. The role of vitaminD deficiency is not clear, although increasing evidence supports an associationwith low vitamin D and decreased muscle mass and strength in elderlypatients, both hallmarks of frailty. It is not known what the role of extrinsicfactors such as smoking, and low physical activity play in the developmentof frailty [13,29].

Part of the difficulty in defining the pathophysiology of frailty is the lack ofspecific markers and symptoms associated with frailty. An increase in inflam-matory markers and many of the mediators associated with frailty are alsofound in other conditions, including normal senescence, cancer, and Alz-heimer’s type dementia (Box 1) [11,12,22].

IDENTIFYING FRAILTYThere is no single test or tool that can be used to diagnose frailty, instead thereare multiple scales and tools available [14,30,31]. Amongst accepted scales, the

Box 1: Nonspecific biomarkers associated with frailty

C-reactive protein

Interleukin-6

Tumor necrosis factor alpha

Neutrophil count

D-dimer

Plasminogen activator inhibitor-1

Testosterone

Insulinlike growth factor-1

Albumin

Vitamin D

Lymphocyte count

Memory/naive CD8 T-cell ratio

Data from Afilalo J, Alexander KP, Mack MJ, et al. Frailty assessment in the cardiovascular care ofolder adults. J Am Coll Cardiol 2014;63(8):747–62.

122 BARNETT

thresholds for identifying frailty may differ depending on the population [1,3].Screening tools may be quite broad, as opposed to more specific scales used tomeasure a treatment effect following intervention. Despite the multitude ofscales, there are 2 main approaches commonly used to define frailty. Theseare the clinical phenotype method and the accumulation deficit model; eachapproach has advantages and disadvantages [32,33].

Clinical phenotype

Fried and colleagues [32] first established the ‘phenotype’ of frailty, using datafrom more than 5000 patients in the Cardiovascular Health Study in 2001(Box 2). The 5 variables associated with the frailty phenotype are:

1. Unintentional weight loss greater than 4.5 kg (10 lb) in prior year2. Symptoms of exhaustion3. Low physical activity4. Poor handgrip strength5. Slow walking speed

Patients are assigned a frailty score of 0–5 based on the presence or absenceof symptoms of weight loss or exhaustion, a description of their activity, or apredetermined cut off for the hand grip or walking speed. These variables areweighted equally, and each 1 is equal to 1 point. Patients with a score of zeroare considered robust or nonfrail, those with 1 or 2 points out of the possible 5are considered ‘prefrail’. Patients who have total score of 3, 4 or 5 of the factorsare considered frail. Although easy to use, this model has been criticized as itrelies heavily on the identification of a decline in muscle mass (sarcopenia)as the central feature of frailty, and excludes any inclusion of cognitive assess-ment or mood. Other tests that rely on a physical assessment include gait speedand handgrip measurements [31,34,35].

Deficit accumulation

The frailty index (FI) was initially created using data from the Canadian Studyof Health and Aging (CSHA), a 5-year prospective cohort study including10,263 patients (Box 3). Ninety 2 patient variables were identified that includeda variety of symptoms, abnormal laboratory values, comorbidities, and a

Box 2: Fried frailty phenotype

1. Unintentional weight loss greater than 4.5 kg (10 lb) in prior year

2. Self-reported exhaustion or lack of energy

3. Diminished grip strength adjusted for sex and size

4. Low physical activity

5. Slow walking speed

From Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci 2001;56:M146–56; with permission.

Box 3: Modified Canadian Frailty Index: accumulation deficit model

1. Diabetes mellitus

2. Chronic obstructive pulmonary disease

3. Congestive heart failure

4. Myocardial infarction

5. Hypertension treated with medication

6. Angina or prior coronary intervention including stent or coronary arterybypass grafting

7. Peripheral vascular disease

8. Impaired sensorium

9. Prior transient ischemic attack or stroke without residual deficit

10. Cerebrovascular accident with residual symptoms

11. Dependent function status

123PERIOPERATIVE FRAILTY

disability assessment. The FI is the number of variables identified, divided bythe total possible (92 for the original test) [1,6,19,30,36]. The higher the score(reflecting more deficits) the more likely it is that a patient is frail. Because thedevelopment of the original model using 92 deficits, several modified FIs havebeen described, including only 70, 30, or even 11 variables. These modifiedfrailty scales are much simpler to calculate and probably have greater utilityin clinical practice. Because the accumulation deficit model (and variants)does not require a physical examination of the patient, this approach hasalso gained popularity for research, using data extraction from medical records.In the USA, the National Surgical Quality Improvement Program (NSQIP) col-lects data from surgical patients in more than 450 hospitals. NSQIP data werecompared with the CSHA data and 11 preoperative variables were identifiedcommon to both programs. These 11 variables were incorporated into a modi-fied FI (mFI) and, when applied to NSQIP data, a positive correlation betweenfrailty and morbidity and mortality following surgery has been found [37–41].

There are other simple ‘bedside’ tests that can be used to assess the func-tional capacity of elderly patients before surgery, many of these are regularlyused by geriatricians but rarely by anesthesiologists. Examples include thetimed get up and go, grip strength and overall walking speed [31,42]. A simplehistory of falls is also an important marker of possible deterioration in indepen-dence that has been associated with increased complications following surgery.These tests may be important additions to the anesthesia preoperative evalua-tion especially when there are lingering questions regarding recovery optionsor choice of surgery [36].

THE ROLE OF THE COMPREHENSIVE GERIATRIC ASSESSMENTAs described earlier, there are multiple scales used to identify frailty, but thesemay only represent a limited evaluation of a patient’s total functional capacity

124 BARNETT

and health. The Comprehensive Geriatric Assessment (CGA) is a multidimen-sional evaluation process covering several distinct domains of an older person’shealth, and can provide a measure of frailty [23,24,40]. The CGA generally in-volves a team-based evaluation including an in-depth assessment of medical,cognitive, psychological, and functional status. A major goal of the CGA isto identify treatable aspects of health issues. The CGA seems to be particularlyvaluable for the assessment of life expectancy and survival. The CGA was notdeveloped as a preoperative screening tool, although recently it has been usedin the presurgical setting with mixed success.

The CGA provides an extensive evaluation of an older patient; the compo-nents may vary depending on the providers, institutions, and the situation. Inone of its most complete forms, the CGA includes an evaluation in as many as11 distinct domains, and involving several types of caregivers, including physi-cians, physical therapists, and social workers. The types of assessment areas rangefrom screening for dementia and delirium to an assessment of sensory perception(hearing and vision). An essential part of all CGAs is an evaluation of mobilityand independence. As stated earlier, the timed get-up-and-go test is a validatedtool used to assess mobility and fall risk. The patient is asked to sit in a chair,walk a distance, make a full turn, and return to the chair. Although simple, thistest requires strength and balance to execute without falling or requiring extraassistance. An assessment of the patient’s independence includes an assessmentof the activities of daily living (ADLs) using, for example, the Barthel index ofADLs, which includes questions about bladder and bowel continence, feeding,dressing, and the ability to go up and down stairs independently. In addition,theCGAmay include an evaluation of the caregiver burden, detailing the supportavailable and required by the patient on a regular basis.

In older patients who have cancer, studies have found that the CGA addspredictive power for morbidity and mortality associated with not only the can-cer but also the treatment. These studies suggest that the CGA may haveparticular value for planning cancer treatments in patients who may be facinga complex course of treatments. However, when applied to the surgical setting,the value-added nature of the CGA has been variable. In one small study, Suhand colleagues [43] studied 60 patients undergoing elective surgery for gyneco-logic cancer who underwent extensive preoperative evaluations using theCGA. They then compared the utility of the complete CGA and all its compo-nents with a simple performance status assessment and instrumental ADLs.The complexity of the surgery predicted the occurrence of major and minorcomplications and the performance status assessment was useful at identifyingpatients at risk of any complication, in contrast with the CGA, which was notvaluable in predicting complications. In contrast, Kim and colleagues [44] per-formed CGA in 140 patients undergoing surgery. The cumulative impairmentidentified within the CGA was independently associated with adverse surgicaloutcomes in elderly patients.

In a study of elderly patients presenting for laparoscopic cholecystectomy,Lasithiotakis and colleagues [37] divided patients into fit or frail groups using

125PERIOPERATIVE FRAILTY

a CGA. The CGA comprised a comprehensive assessment including func-tional assessment tools of independence, an assessment of comorbidity usingthe Charlson comorbidity index, a nutritional appraisal and a cognitivescreen using the mini–mental state examination. If patients had any criteriathat were frail they were considered frail; to be considered fit they had tomeet all the predefined criteria. The main outcome examined was the occur-rence of postoperative complications within 30 days. Fifty-seven patientscompleted the preoperative CGA, and of these 56% were considered frailversus 44% who were fit. Postoperative complications, including length ofstay, were significantly higher in frail patients than in fit patients: 85% versus15%, respectively (P<.022). This study supports the theory that frail patientshave more complications and potentially longer lengths of stay and thereforegreater costs. Other studies have also shown that identifying frailty, usingan individual test or the CGA approach, can provide an improved estimateof risk compared with a patient’s age or the American Society of Anesthesi-ology (ASA) classification alone [16,19,38,45].

STRENGTH AND GAIT SPEEDThe phenotype frailty evaluation and the CGA may both include a test of gaitspeed and mobility. For the Fried phenotype, a slow gait speed is the strongestpredictor of chronic disability and institutionalization. In community-dwelling el-ders, slow gait speed is also associated with greater risk of cognitive impairmentand disability. Although a valuable marker, gait speed is nonspecific and multipledisorders can contribute to a slow gait speed [31,34,42]. In most studies the timeto walk 5 m on a flat surface is measured. Hand grip, another strength-relatedmarker, also has good predictive value on outcomes [35].

SARCOPENIANormal aging is associated with a decrease in skeletal muscle quality andmass, and with associated strength and function. This condition is knownas sarcopenia, which can be primary or secondary. Primary sarcopenia seemsto be associated with age-related inactivity, and is associated with weakeningand impaired function; secondary sarcopenia is more active and is associatedwith alterations in metabolism, referred to as cachexia. After the seventhdecade of life, the rate of loss of function versus muscle mass is accelerated,which has important implications for mobility and functional independence[1,4,12]. In addition, the length of time to recovery of muscle function isimpaired in older patients, and even a few days of bed rest or immobilitycan lead to a significant loss of muscle function [46,47]. Sarcopenia is animportant feature of frailty and a predictor of mortality and complicationsafter surgery. Although classic sarcopenia and frailty are characterized byweight loss and a low body mass index (BMI), sarcopenic obesity has alsorecently been recognized in older obese patients with high BMI but low mus-cle mass.

126 BARNETT

CARDIOVASCULAR DISEASE AND FRAILTYGeneral increases of inflammatory biomarkers such as interleukin-6, C-reactiveprotein, and various cytokines, and other alterations in immune modulationcontribute to the development of atherosclerosis and damage to the cardiovas-cular system [22]. The frailty condition shares many of these markers, and sub-clinical cardiovascular disease (CVD) is commonly found in frail patients[48,49]. Frailty is becoming an increasingly important consideration in cardio-vascular patients, affecting prognosis and treatment choices [27,40,45,48]. Esti-mates suggest that frailty occurs in 25% to 50% of patients with CVD. Khanand colleagues [21] found that in community-dwelling elders, moderate to se-vere frailty was associated with a greater than 30% risk of developing clinicalheart failure. The underlying risk and association of CVD and frailty is impor-tant to the preoperative risk for patients undergoing anesthesia and surgery,especially in patients with congestive heart failure [12,22,45,49–51].

PREOPERATIVE IDENTIFICATION OF VULNERABLE PATIENTSAs described earlier, frailty is associated with increased complications followingsurgery, and preoperative identification of the frail patient ideally leads to effec-tive preventative interventions. Using the mFI to assess the degree of frailtypresent in patients undergoing laparoscopic colorectal surgery, Keller and col-leagues [39] found that higher frailty score was associated with longer length ofstay, and that patients with a 0 score on the frailty assessment were dischargedthe earliest. The modified Hopkins Score criteria include a measure of shrink-ing or weight loss, decreased grip strength, exhaustion, low activity, and slowwalking speed. The advantage of the modified frailty score described by Kelleris the simplicity to perform, requiring little or no additional expense. The Hop-kins Score alone is a robust predictor of postoperative complications. Addingother predictors of postoperative complications such as albumin, C-reactiveprotein, the glomerular filtration rate alone, and classic ADLs did not improvethe predictive power of the mFI. At present there is little to do to reverse frailtybefore surgery, but this study and others like it suggest that a frailty assessmentbefore surgery can predict who will need additional resources after surgery andwhich are the most vulnerable populations [19,38].

Robinson and colleagues [6] studied the incidence of postoperative complica-tions in elderly patients after colorectal and cardiovascular surgery. They usedan array of 7 different frailty tests and categorized patients as nonfrail, prefrail,and frail (Box 4). For colorectal patients, complications occurred in 21% of thenonfrail, 40% of the prefrail, and 58% of the frail groups (P ¼ .016). The inci-dence of complications in patients having cardiac surgery was 17% for nonfrailversus 56% in frail patients (P < .001). Lengths of stay were longer and read-missions were more common in frail patients in both surgical types.

ANESTHESIA AND THE FRAIL PATIENTThere is no single approach to frail geriatric patients; instead meticulous care ofelderly patients is important. Frail patients are patients with limited physiologic

Box 4: Frailty tests

1. Timed Up and Go Normal less than 15 seconds. This test is a measure of thetime in seconds from sitting and rising from a chair to a standing position andwalking 3 m (10 feet) on a flat surface, returning to the chair, and sittingagain.

2. Independence of activities by the Katz Score. ADLs: bathing, feeding, dres-sing, transferring, walking, and toileting. Abnormal score defined as depen-dence of 1 or more activity.

3. Cognition test using the Mini-Cog test, which includes the 3-paired item recalland clock drawing.

4. Comorbidity assessment using the Charlson Index. This index measuresburden of disease using 19 categories of comorbidity.

5. Chronic disease anemia, defined as hematocrit level of less than 35%.

6. A low albumin of less than 3.4 g/dL, which is a measure of nutrition.

7. History of 1 or more falls in the last 6 months.

Patients are grouped by number of positive characteristics: 0–1, nonfrail; 2–3 positives,prefrail; 4–7 abnormalities, frail.

From Robinson TN, Wu DS, Pointer L, et al. Simple frailty score predicts postoperative com-plications across surgical specialties. Am J Surg 2013;206:544–50; with permission.

127PERIOPERATIVE FRAILTY

reserve, who are thus vulnerable to even the slightest insult; for example,through hypotension or hypovolemia. Frail patients undergoing surgery andanesthesia carry an increased risk from complications and poor outcomes,including delirium. The contribution of the intraoperative anesthetic to theseadverse outcomes is not well understood. In adults, deep anesthesia, defined us-ing the bispectral index (BIS), has been associated with increased mortality in pa-tients, especially those with low blood pressure and hematocrit. From thesestudies it is unclear whether the low BIS in these patients was a marker of overallpoor preoperative status or a reflection of the impact of anesthetic agents on thebrain [52]. Several studies have recently assessed the relationship between thedepth of anesthesia and the risk of developing cognitive dysfunction followingsurgery. Siebert and colleagues [53] randomized elderly patients having hip frac-ture repair under spinal anesthesia to 2 different levels of sedation. Both groupsreceived sedation with propofol and/or midazolam. The incidence of deliriumwas 50% less in the light sedation group, in which a BIS greater than 50 wasmain-tained, versus the deep sedation group, which had BIS less than 50. On follow-upthe 1-year mortality was 50% higher in patients withmultiple comorbidities in thedeep sedation group versus the light sedation group [51]. In a series of otherstudies of general anesthesia with anesthetic gases, patients who are maintainedwith higher BIS levels (45 or more) have a faster emergence and less likelihood ofshort-term delirium or longer-term postoperative cognitive dysfunction. Thesestudies have not been directed at frail patients but, given the known increasedrisk of delirium and the reduction in reserve function, it is intuitive that these

Box 5: Elements of prehabilitation programs

1. Walking 15 to 20 minutes 3 times per week

2. Strength exercises: upper arm and shoulder; lower limbs including hamstringcurls, ankle pronation

3. Abdominal breathing exercises

Data from Lee DH, Buth KJ, Martin BJ, et al. Frail patients are at increased risk for mortality andprolonged institutional care after cardiac surgery. Circulation 2010;121:973–8; and KortebeinP, Ferrando A, Lombeida J, et al. Effect of 10 days of bed rest on skeletal muscle in healthy olderadults. JAMA 2007;297:1772–4.

128 BARNETT

patients will require less anesthesia. It is well known that the minimum alveolarconcentration (MAC) of anesthesia is less in older patients, and these studies sug-gest there are advantages to monitoring the depth of anesthesia in very old andfrail patients.

PREHABILITATION AND ENHANCED RECOVERY AFTERSURGERY PROGRAMSPhysical deconditioning (ie, a history of early exhaustion, diminished gripstrength, weight loss, and generalized poor nutrition) is central in the identi-fication of frail patients. Frail patients, especially those with sarcopenia, are athigh risk of rapid deconditioning after any period of immobility [6]. Prehabi-litation refers to a concentrated exercise program for patients before surgery,in contrast with the traditional rehabilitative physiotherapy and interventionsoffered after surgery (Box 5). It is known that resistance training in older frailcommunity patients can lead to improvements in physical function [54,55].This approach has also been tried in frail orthopedic patients. Some studieshave shown benefit for patients undergoing elective knee surgery who un-derwent strength and endurance training for several weeks before electivesurgery [56]. However, the feasibility and cost of prehabilitation for generalsurgery patients have yet to be established. It might be that, in selectedsurgeries, a period of prehabilitation can improve functional outcomes.ERAS refers to the enhanced recovery after surgery [6,41,57] programs.These clinical pathways guide preoperative and postsurgical care of patients,and improved outcomes have been shown for surgeries such as joint replace-ment, although most are not specific to frail patients [10].

SUMMARYFrailty is an important syndrome in the geriatric population. The occurrence offrailty has important prognostic implications for patients in general and inparticular at the time of surgery. Anesthesiologists should be able to recognizeand diagnose frailty in older patients and understand the implications for out-comes. Measuring frailty may contribute to decision-making capability for pa-tients and their families, as well as anesthesiologists and surgeons. Future

129PERIOPERATIVE FRAILTY

research should be directed toward strategies to reverse frailty and reducecomplications and readmissions in frail patients undergoing surgery.

References

[1] Hubbard RE, Story DA. Patient frailty: the elephant in the operating room. Anaesthesia

2014;69(Suppl 1):26–34.[2] Amrock LG, Deiner S. The implication of frailty on preoperative risk assessment. Curr Opin

Anaesthesiol 2014;27:330–5.[3] Partridge JS, Harari D, Dhesi JK. Frailty in the older surgical patient: a review. Age Ageing

2012;41(2):142–7.[4] Joseph B, Pandit V, Sadoun M, et al. Frailty in surgery. J Trauma Acute Care Surg

2014;76(4):1151–6.[5] Peden CJ, Grocot MP. National Research Strategies: what outcomes are important in

peri-operative elderly care? Anaesthesia 2014;69(Suppl 1):61–9.[6] Robinson TN, Wu DS, Pointer L, et al. Simple frailty score predicts postoperative com-

plications across surgical specialties. Am J Surg 2013;206:544–50.[7] Robinson TN, Eiseman B, Wallace JI, et al. Redefining geriatric preoperative assessment

using frailty, disability and co-morbidity. Ann Surg 2009;250:449–55.[8] Bakker FC, Robben SH, Olde Rikkert MG. Effects of hospital-wide interventions to

improve care for frail older inpatients: a systematic review. BMJ Qual Saf 2011;20:680–91.

[9] Chin A, PawMJ, Dekker JM, et al. How to select a frail elderly population? A comparison ofthree working definitions. J Clin Epidemiol 1999;52:1015.

[10] Carli F, Brown R, Kennepohl S. Prehabilitation to enhance postoperative recovery for anoctogenarian following robotic-assisted hysterectomy with endometrial cancer. Can JAnaesth 2012;59:779–84.

[11] Fedarko NS. The biology of aging and frailty. Clin Geriatr Med 2011;27:27–37.[12] Fulop T, Larbi A, Witkowski JM, et al. Aging, frailty and age-related diseases. Bio-

gerontology 2010;11:547–63.[13] Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and

coagulation systems with and without clinical comorbidities: results from the Cardio-vascular Health Study. Arch Intern Med 2002;162:2333–41.

[14] Abellan van Kan G, Rolland Y, Bergman H, et al. The I.A.N.A task force on frailty assess-ment of older people in clinical practice. J Nutr Health Aging 2008;12:29–37.

[15] Bergman H, Ferrucci L, Guralnik J, et al. Frailty: an emerging research and clinical para-digm–issues and controversies. J Gerontol A Biol Sci Med Sci 2007;62:731–7.

[16] Shamliyan T, Talley KM, Ramakrishnan R, et al. Association of frailtywith survival: a system-atic literature review. Ageing Res Rev 2012;12:719–36.

[17] Chikwe J, Adams DH. Frailty: the missing element in predicting operative mortality. SeminThorac Cardiovasc Surg 2010;22:109–10.

[18] Fried LP, Ferrucci L, Darer J, et al. Untangling the concepts of disability, frailty, and comor-bidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci2004;59:255–63.

[19] Revenig LM, Canter DJ, Taylor MD, et al. Too frail for surgery? Initial results of a large multi-disciplinary prospective study examining preoperative variables predictive of poor surgi-cal outcomes. J Am Coll Surg 2013;217:665–70.

[20] Collard RM, Boter H, Schoevers RA, et al. Prevalence of frailty in community-dwelling olderpersons: a systematic review. J Am Geriatr Soc 2012;60:1487–92.

[21] Khan H, Kalogeropoulos AP, Georgiopoulou VV, et al. Frailty and risk for heart failure inolder adults: the Health, Aging, and Body Composition Study. Am Heart J 2013;166:887–94.

[22] Afilalo J, Alexander KP, Mack MJ, et al. Frailty assessment in the cardiovascular care ofolder adults. J Am Coll Cardiol 2014;63(8):747–62.

130 BARNETT

[23] Sundermann S, Dademasch A, Praetorius J, et al. Comprehensive assessment of frailtyfor elderly high-risk patients undergoing cardiac surgery. Eur J Cardiothorac Surg2011;39:33–7.

[24] Sundermann S, Dademasch A, Rastan A, et al. One-year follow-up of patients undergoingelective cardiac surgery assessed with the comprehensive assessment of frailty test and itssimplified form. Interact Cardiovasc Thorac Surg 2011;13:119–23.

[25] Stortecky S, Schoenenberger AW,Moser A, et al. Evaluation of multidimensional geriatricassessment as a predictor of mortality and cardiovascular events after transcatheter aorticvalve implantation. JACC Cardiovasc Interv 2012;5:489–96.

[26] Klein BE, Klein R, KnudtsonMD, et al. Frailty, morbidity and survival. ArchGerontolGeriatr2005;41:141–9.

[27] Woods NF, Lacroix AZ, Gray SL, et al. Frailty: emergence and consequences in womenaged 65 and older in the Women’s Health Initiative Observational Study. J Am GeriatrSoc 2005;53:1321–30.

[28] Baylis D, Bartlett DB, Syddall HE, et al. Immune-endocrine bio-markers as predictors offrailty and mortality: a 10-year longitudinal study in community-dwelling older people.Age (Dordr) 2013;35:963–71.

[29] Barzilay JI, Blaum C, Moore T, et al. Insulin resistance and inflammation as precursors offrailty: the cardiovascular health study. Arch Intern Med 2007;167:635–41.

[30] Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicinedefined by frailty. Clin Geriatr Med 2011;27:17–26.

[31] Volpato S, Cavalieri M, Sioulis F, et al. Predictive value of the short physical performancebattery following hospitalization in older patients. J Gerontol A Biol Sci Med Sci 2011;66:89–96.

[32] Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci 2001;56:M146–56.

[33] Bandeen-Roche K, Xue QL, Ferrucci L, et al. Phenotype of frailty: characterization in thewomen’s health and aging studies. J Gerontol A Biol Sci Med Sci 2006;61:262–6.

[34] Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assess-ing lower extremity function: associationwith self-reported disability and prediction of mor-tality and nursing home admission. J Gerontol 1994;49:M85–94.

[35] Ling CH, Taekema D, de Craen AJ, et al. Handgrip strength and mortality in the oldest oldpopulation: the Leiden 85-Plus study. CMAJ 2010;182:429–35.

[36] de VriesNM, Staal JB, van RavensbergCD, et al. Outcome instruments tomeasure frailty: asystematic review. Ageing Res Rev 2011;10:104–14.

[37] Lasithiotakis K, Petrakis J, Venianaki M, et al. Frailty predicts outcome of elective laparo-scopic cholecystectomy in geriatric patients. Surg Endosc 2013;27(4):1144–50.

[38] Adams P, Ghanem T, Stachler R, et al. Frailty as a predictor of morbidity and mortality ininpatient head and neck surgery. JAMA Otolaryngol Head Neck Surg 2013;139(8):783–9.

[39] Keller DS, Bankwitz B, Nobel T, et al. Using frailty to predict who will fail early dischargeafter laparoscopic colorectal surgery with an established recovery pathway. Dis ColonRectum 2014;57:337–42.

[40] Afilalo J, Karunananthan S, Eisenberg MJ, et al. Role of frailty in patients with cardiovas-cular disease. Am J Cardiol 2009;103:1616–21.

[41] Perera S, Mody SH,Woodman RC, et al. Meaningful change and responsiveness in com-mon physical performance measures in older adults. J Am Geriatr Soc 2006;54:743–9.

[42] Afilalo J, EisenbergMJ, Morin JF, et al. Gait speed as an incremental predictor of mortalityand major morbidity in elderly patients undergoing cardiac surgery. J Am Coll Cardiol2010;56:1668–76.

[43] Suh DH, Kim JW, Kim SH, et al. Pre-and intra-operative variables associated with surgicalcomplications in elderly patients with gynecologic cancer: the clinical value of comprehen-sive geriatric assessment. J Geriatr Oncol 2014;5(3):315–22.

131PERIOPERATIVE FRAILTY

[44] Kim K, Park KH, Koo KH, et al. Comprehensive geriatric assessment can predict postoper-ative morbidity and mortality in elderly patients undergoing elective surgery. Arch Geron-tol Geriatr 2013;56:507–12.

[45] Lee DH, Buth KJ, Martin BJ, et al. Frail patients are at increased risk for mortality and pro-longed institutional care after cardiac surgery. Circulation 2010;121:973–8.

[46] Kortebein P, Ferrando A, Lombeida J, et al. Effect of 10 days of bed rest on skeletal musclein healthy older adults. JAMA 2007;297:1772–4.

[47] Wall BT, Dirks ML, van Loon LJ. Skeletal muscle atrophy during short-term disuse: implica-tions for age-related sarcopenia. Ageing Res Rev 2013;12:898–906.

[48] Newman AB, Gottdiener JS, Mcburnie MA, et al. Associations of subclinical cardiovascu-lar disease with frailty. J Gerontol A Biol Sci Med Sci 2001;56:M158–66.

[49] Cacciatore F, Abete P, Mazzella F, et al. Frailty predicts long-term mortality in elderly sub-jects with chronic heart failure. Eur J Clin Invest 2005;35:723–30.

[50] Rozzini R, Sabatini T, Frisoni GB, et al. Frailty is a strong modulator of heart failure-associated mortality. Arch Intern Med 2003;163:737–8.

[51] Radtke FM, Franck M, Lendner JL, et al. Monitoring depth of anaesthesia in a randomizedtrial decreases the rate of postoperative delirium but not postoperative cognitive dysfunc-tion. Br J Anaesth 2013;110(S1):i98–105.

[52] Sieber Fe, Zakriya KJ, Gottschalk A, et al. Sedation depth during spinal anesthesia and thedevelopment of postoperative delirium in elderly patients undergoing hip fracture repair.Mayo Clin Proc 2010;85:18–26.

[53] Brown CH, Azman AS, Gottschalk A, et al. Sedation depth during spinal anesthesia andsurvival in elderly patient undergoing hip fracture repair. Anesth Analg 2014;118:977–80.

[54] Latham NK, Bennett DA, Stretton CM, et al. Systematic review of progressive resistancestrength training in older adults. J Gerontol A Biol Sci Med Sci 2004;59:48–61.

[55] Gill TM, Baker DI, Gottschalk M, et al. A program to prevent functional decline in physi-cally frail, elderly persons who live at home. N Engl J Med 2002;347:1068–74.

[56] Huang SW, Chen PH, Chou YH. Effects of a preoperative simplified home rehabilitationeducation program on length of stay of total knee arthroplasty patients. Orthop TraumatolSurg Res 2012;98(3):259–64.

[57] Zhuang CL, Ye XZ, Zhang XD, et al. Enhanced recovery after surgery programs versustraditional care for colorectal surgery: a meta-analysis of randomized controlled trials.Dis Colon Rectum 2013;56:667–78.