Abstract
Introduction
Our purpose was to determine the relationship between pre-operative frailty and the occurrence of postoperative complications following colorectal and cardiac operations.
Study Design
Patients ≥65 years undergoing elective colorectal or cardiac surgery were enrolled. Seven baseline frailty traits were measured pre-operatively: Katz Score ≤5, Timed Up-and-Go ≥15 seconds, Charlson Index ≥3, anemia<35%, Mini-Cog score ≤3, albumin<3.4gm/dL and ≥1 fall within six-months. Patients were categorized by the number of positive traits: non-frail: 0–1 trait, pre-frail: 2–3 traits and frail: ≥4 traits.
Results
201 subjects (age 74±6 years) were studied. Preoperative frailty was associated with increased postoperative complications following colorectal (non-frail 21%, pre-frail 40% and frail 58%; p=0.016) and cardiac operations (non-frail 17%, pre-frail 28% and frail 56%; p<0.001). This finding in both groups was independent of advancing age. Frail individuals in both groups had longer hospital stays and higher 30-day readmission rates. Receiver operating characteristic curves examining frailty’s ability to forecast complications were: colorectal (0.702; p=0.004) and cardiac (0.711; p<0.001).
Conclusion
A simple pre-operative frailty score defines older adults at higher risk for postoperative complications across surgical specialties.
INTRODUCTION
To operate or not to operate; that is the question faced by surgeons and other clinicians when an older adult presents with the indication for a major elective operation. Given that more than one third of current operations in the United States are performed in individuals 65 years and older1 (a number which is expected to increase in the next few decades2), this debate is occurring with increasing frequency. Colorectal and cardiac operations are common major elective operations that have the higher complication rates in older adults.3–4 To decide whether to recommend an operation, the clinician pre-operatively attempts to forecast the risk of postoperative adverse outcomes.
Current pre-operative risk stratification strategies do not capture physiologic compromise unique to older adults. Traditional methods typically assess single end-organ organ specific physiologic compromise (e.g., the heart5) rather than more global physiologic compromise relevant to the whole patient. Frailty is a term used for older adults and recognizes global limited reserve to withstand stressors. Frailty represents a state of reduced physiologic reserve associated with increased susceptibility to disability.6 By definition, a frail individual is highly susceptible to poor healthcare outcomes.
The purpose of this study was to determine the relationship of frailty and the occurrence of post-operative complications in two different surgical specialties. In patients undergoing elective colorectal and cardiac operations, the specific aims were to determine the relationship of baseline pre-operative frailty to (1) the occurrence of one or more post-operative complications, (2) length of stay, and (3) 30-day readmission rate.
METHODS
This was a prospective cohort study performed at the Denver Veterans Affairs Medical Center. Regulatory approval was obtained through the Colorado Multiple Institutional Review Board (COMIRB 08–1071). Inclusion criteria were patients ≥65 years of age undergoing elective colorectal or cardiac operations. Elective cardiac and colon operations were studied because these are two common operations performed at our institution which require inpatient stays and are complex enough operations to result in postoperative complications. Exclusion criteria were pelvic exenterations, cardiac operations with thoracic aneurysm repairs, and acute blood loss anemia (in whom anemia is not from chronic disease). Emergent operations (defined as clinical conditions that mandate surgery within 12 hours of admission or cardiac catheterization) and urgent operations (clinical conditions that mandate surgery between 12 and 72 hours of admission or cardiac catheterization) were excluded because accurate frailty data cannot be measured (e.g., an accurate mini-cog score cannot be obtained from a stressed patient hospitalized for sepsis or a myocardial infarction which leads to an urgent or emergent operation). Subjects were recruited between January 2007 and November 2010.
To quantify the presence of frailty in an elderly individual, abnormalities across frailty domains (e.g, function, cognition, nutrition, chronic disease burden, geriatric syndromes) are summed and the accumulation of frailty characteristics is used to describe the level of an individual’s frailty.7–8 (see Figure 19) Frailty characteristics were measured pre-operatively, at baseline prior to an elective operation in all subjects. The seven frailty characteristics which our previous work has found to be most closely associated with adverse post-operative outcomes were employed in this study.10–11 Cutoff values that define an abnormal frailty characteristic used in this study are the same as our three prior studies.10–12 Participants were grouped based on their burden of frailty: Non-Frail (0 and 1 abnormal characteristics), Pre-Frail (2 and 3 abnormal characteristics) and Frail (4 to 7 abnormal characteristics).
Figure 1. Summing Geriatric Assessment Deficits to Determine Post-Operative Risk: The Balance Scale Analogy.
The analogy of a bar scale that weighs an individual’s surgical risk is useful to understand the concept of summing abnormal geriatric assessment domains (or deficits) to predict postoperative risk.9 Blocks represent geriatric assessment domains (e.g., function, cognition, nutrition, co-morbidity burden and geriatric syndromes). Blocks are place opposite one another on the bar scale depending on whether the domain was measured as a normal characteristic or an abnormal deficit. Two older adults’ assessments are depicted in this graphic. On the left is a non-frail individual; the majority of the measured geriatric domains are normal resulting in tilting the scale toward “better” post-operative outcomes. In contrast, on the right is a frail individual; the majority of geriatric domains are abnormal (or deficits) resulting in tilting the scale toward “poor” post-operative outcomes.
The seven frailty characteristics measured and their cutoff values were: The Timed Up-and Go measures the time needed to stand up from a chair, walk 10 feet, return to the chair, and sit; an abnormal score was defined as ≥15 seconds. The Katz Score measures independence of activities of daily living (bathing, dressing, transferring, walking, toileting, and feeding);13 an abnormal score was defined as dependence in one or more activity of daily living. The Mini-Cog measures cognition using a paired three-item recall and clock draw task;14 abnormal cognition was defined as a Mini-Cog score ≤3. The Charlson Index measures burden of disease by summing 19 categories of co-morbidities weighted on their risk of one-year mortality;15 an abnormal chronic disease burden was defined as a Charlson score ≥3. Anemia of chronic disease also measured disease burden; anemia was defined as Hematocrit < 35%. Poor nutrition was defined as serum albumin level below 3.4 g/dL. The geriatric syndrome of falls16 was measured by asking the individual how many times they have fallen in the six-months prior to surgery; a positive score of falls was defined as ≥1 fall in the six-months prior to the operation. Frailty characteristics were measured within thirty-days of the operation performed. The average required to collect this information was around 5 minutes per patient. Frail individuals take more time to complete the Mini-Cog and timed up-and-go measurements.
Routine pre-, intra- and post-operative events were recorded prospectively. Postoperative complications were defined using Veterans Affairs Surgery Quality Improvement Program (VASQIP)17 definitions: cardiac (cardiac arrest requiring cardiopulmonary resuscitation [CDARREST] or myocardial infarction [CDMI]); respiratory (pneumonia [OUPNEUMO], pulmonary embolism [PULEMBOL] or reintubation for respiratory/cardiac failure [REINTUB]); renal insufficiency [RENAINSF]; neurologic (cerebral vascular accident/stroke [CNSCVA] or coma>24 hours [CNSCOMA]); post-operative infection (deep wound surgical site infection [WNDINFD], superficial surgical site infection [SUPINFEC] or urinary tract infection [URNINFEC]); sepsis [OTHSYSEP]; deep vein thrombosis [OTHDVT]; and re-operation (Return to OR [RETURNOR]). Post-operative outcomes recorded met criteria of a moderate or more severe complication (mild complications were not included) by the Accordion Severity Classification.18 By including only moderate or more severe complications by the Accordion classification, infections included in the analysis had to be treated with antibiotics as simply opening a wound without antibiotic treatment did not qualify as a moderate complication. Other outcomes recorded were length of hospital stay and 30-day readmission rate.
Statistical analysis was performed using medians and the Kruskal-Wallis analysis of variance test (a test used for comparing more than two groups with data that is not normally distributed) for continuous variables. Either a Fischer’s exact or Mantel-Haenzsel Chi-Squared test was used for categorical variables. The independent variable was frailty burden represented by the non-frail, pre-frail and frail groups. The primary outcome variable was the occurrence of one or more post-operative complications. Logistic regression was used to control for effect of advancing age on the relationship of frailty burden and the occurrence of one or more postoperative complications. Receiver operating characteristic (ROC) curves were performed to evaluate the quality of performance of accumulation of frailty characteristics (defined in the ROC analysis as a range from 0 if the subject had no positive characteristics to 7 if the subject scored positive in all 7 of the frailty characteristics) to the occurrence of one or more postoperative complications in both surgical groups. Statistical significance was set at p<0.05. Results were reported as mean ± standard deviation.
RESULTS
A total of 201 subjects were studied with an average age of 74 ± 6 year and 196 (98%) were male. Colorectal operations were performed in 72 (36%) and cardiac operations in 129 (64%) of the total group. A list of operation performed for the colorectal group included: 36% (26) right colectomies, 22% (16) left colectomies, 31% (22) sigmoid colectomies, and11% (8) colostomy takedowns. A list of operations performed in the cardiac group included 58% (75) coronary artery bypass operations, 28% (36) cardiac valve operations, and 14% (18) combined coronary artery bypass and cardiac valve operations. Baseline frailty groups for the whole study population were non-frail 105 (52%), pre-frail 40 (20%), and frail 56 (28%). The average length of stay was 9 ± 7 days and the overall rate of thirty-day readmission was 14% (29). Hospital mortality occurred 2% (4) of the entire group, which included 3% (2) in the colorectal group and 2% (2) in the cardiac group.
Baseline demographics are reported for the colorectal and cardiac surgery populations. (see Table 1) In the colorectal surgery population, increasing burden of frailty was associated with advancing age (p<0.001). Other co-morbidities were similar when comparing the three frailty colorectal groups. In the cardiac surgery population, age and co- morbidities were similar when comparing the three frailty groups except there was a higher incidence of prior stroke in the frail group (p=0.009).
Table 1.
Baseline Characteristics of Patients and Operations
| Total | Non-Frail | Pre-Frail | Frail | p-value | |
|---|---|---|---|---|---|
| Colorectal Operations | (n=72) | (n=33) | (n=15) | (n=24) | |
| Pre-Op Variables | |||||
| Age (years) | 74±6 | 70±5 | 75±6 | 79±6 | <0.001 |
| Creatinine (mg/dL) | 1.2±0.5 | 1.1±0.2 | 1.1±0.3 | 1.4±0.8 | 0.542 |
| Stroke | 7% (5) | 6% (2) | 7% (1) | 8% (2) | 1.000 |
| Hypertension | 74% (53) | 67% (22) | 80% (12) | 80% (19) | 0.469 |
| COPD | 21% (15) | 15% (5) | 13% (2) | 33% (8) | 0.180 |
| Diabetes Mellitus | 13% (9) | 12% (4) | 7% (1) | 17% (4) | 0.732 |
| Operations | 0.683 | ||||
| Right Colectomy | 36% (26) | 50% (13) | 31% (8) | 19% (5) | |
| Left Colectomy | 22% (16) | 50% (8) | 19% (3) | 31% (5) | |
| Sigmoid Colectomy | 31% (22) | 45% (10) | 18% (4) | 36% (8) | |
| Colostomy Takedown | 11% (8) | 38% (3) | 13% (1) | 50% (4) | |
| Laparoscopic (not open) | 64% (46) | 68% (23) | 73% (11) | 52% (12) | 0.350 |
| OR Time (minutes) | 168±39 | 167±38 | 174±44 | 164±39 | 0.768 |
| Blood Loss (mL) | 166±126 | 144±91 | 177±121 | 190±167 | 0.383 |
| Cardiac Operations | (n=129) | (n=72) | (n=25) | (n=32) | |
| Pre-Op Variables | |||||
| Age (years) | 73±6 | 73±5 | 75±5 | 75±6 | 0.078 |
| Creatinine (mg/dL) | 1.4±0.9 | 1.3±0.4 | 1.6±1.3 | 1.7±1.1 | 0.090 |
| Stroke | 9% (12) | 3% (2) | 16% (4) | 19% (6) | 0.009 |
| Hypertension | 91% (117) | 89% (64) | 96% (24) | 91% (29) | 0.651 |
| COPD | 29% (38) | 28% (20) | 32% (8) | 31% (10) | 0.894 |
| Diabetes Mellitus | 41% (53) | 35% (25) | 48% (12) | 50% (16) | 0.253 |
| Operations | 0.984 | ||||
| CABG | 58% (75) | 57% (43) | 19% (14) | 24% (18) | |
| Cardiac Valve | 28% (36) | 53% (19) | 19% (7) | 28% (10) | |
| CABG & Valve | 14% (18) | 56% (10) | 22% (4) | 22% (4) | |
| OR Time (minutes) | 319±88 | 327±89 | 329±87 | 292±84 | 0.135 |
Acronyms: COPD = chronic obstructive pulmonary disease; OR = operating room; CABG = coronary artery bypass graft.
One or more complications occurred in 32% (64) of patients in the entire group, 38% (27) in the colorectal group and 29% (37) in the cardiac surgery group. As frailty burden increases, one or more complications was more likely to occur in both the colorectal (p=0.016) and cardiac (p<0.001) surgery groups. (see Table 2) Infection was the most common complication in both surgical groups. Because increasing age was significantly related to increasing frailty burden in the colorectal group (p<0.001, see Table 1), logistic regression was used to control for the effect of advancing age on the relationship between increasing frailty burden and the occurrence of one or more post-operative complications in both surgical groups. For the colorectal operation cohort with the non-frail group as the reference, there was a 1.096 increase in complications (95% CI: 0.989, 1.215; p=0.081) for every one year increase in age, frail individuals were 13.360 times as likely to have a complication (95% CI: 2.557, 69.807; p=0.002) and pre-frail individuals were 3.400 times as likely to have a complication (95% CI: 0.772, 14.969; p=0.106). For the cardiac operation cohort with the non-frail group as the reference, there was a 1.015 increase in complications (95% CI: 0.943, 1.092; p=0.697) for every one year increase in age, frail individuals were 6.697 times as likely to have a complication (95% CI: 2.565, 17.483; p<0.001) and pre-frail individuals were 3.343 times as likely to have a complication (95% CI: 1.090, 10.255; p=0.035). Length of stay increased with higher accumulation of frailty characteristics in both the colorectal (p<0.001) and cardiac (p=0.026) surgery groups. Rate of thirty-day readmission increased with higher accumulation of frailty characteristics in both the colorectal (p<0.046) and cardiac (p=0.014) surgery groups. (see Table 3)
Table 2.
Baseline Frailty and Post-Operative Outcomes
| Total | Non-Frail | Pre-Frail | Frail | p-value | |
|---|---|---|---|---|---|
| Colorectal Operations | (n=72) | (n=33) | (n=15) | (n=24) | |
| One or more complications | 38% (27) | 21% (7) | 40% (6) | 58% (14) | 0.016 |
| Cardiac | 3% (2) | 0% (0) | 0% (0) | 8% (2) | |
| DVT | 1% (1) | 0% (0) | 0% (0) | 4% (1) | |
| Sepsis | 11% (8) | 3% (1) | 7% (1) | 25% (6) | |
| Post-Op Infection | 25% (18) | 18% (6) | 27% (4) | 33% (8) | |
| Renal Disease | 3% (2) | 0% (0) | 0% (0) | 8% (2) | |
| Respiratory | 8% (6) | 0% (0) | 0% (0) | 25% (6) | |
| Neurological | 1% (1) | 0% (0) | 0% (0) | 4% (1) | |
| Re-Operation | 8% (6) | 3% (1) | 0% (0) | 21% (5) | |
| Hospital Stay (days) | 9±8.0 | 6±3.6 | 8±6.1 | 14±11.0 | <0.001 |
| 30-Day Readmission | 15% (11) | 6% (2) | 20% (3) | 29% (7) | 0.046 |
| Cardiac Operations | (n=129) | (n=72) | (n=25) | (n=32) | |
| One or more complications | 29% (37) | 17% (12) | 28% (7) | 56% (18) | <0.001 |
| Cardiac | 4% (5) | 1% (1) | 4% (1) | 9% (3) | |
| DVT | 2% (2) | 1% (1) | 0% (0) | 3% (1) | |
| Sepsis | 3% (4) | 4% (3) | 0% (0) | 3% (1) | |
| Post-Op Infection | 13% (17) | 8% (6) | 8% (2) | 28% (9) | |
| Renal Disease | 4% (5) | 1% (1) | 0% (0) | 13% (4) | |
| Respiratory | 5% (6) | 3% (2) | 4% (1) | 9% (3) | |
| Neurological | 2% (3) | 1% (1) | 0% (0) | 6% (2) | |
| Re-Operation | 5% (7) | 6% (4) | 4% (1) | 6% (2) | |
| Hospital Stay (days) | 10±5.5 | 9±4.5 | 10±4.4 | 12±7.5 | 0.026 |
| 30-Day Readmission | 14% (18) | 7% (5) | 16% (4) | 28% (9) | 0.014 |
Acronyms: DVT = Deep Venous Thrombosis.
Receiver operating characteristic (ROC) curves were performed for both surgical groups. (see Figure 2). The area under the curve was compared to the null hypothesis where the area is 0.5. For colorectal operations group, area under the curve equaled 0.702 (95% CI: 0.576, 0.828; p=0.004). For the cardiac operations group, area under the curve equaled 0.711 (95% CI: 0.606, 0.817; p<0.001).
Figure 2. Receiver Operating Characteristic (ROC) Curves.
The area under the curve is compared to the null hypothesis (diagonal line) where the true area is 0.5. For colorectal operations group, area under the curve equals 0.702 (95% CI: 0.576, 0.828; p=0.004). For the cardiac operations group, area under the curve equals 0.711 (95% CI: 0.606, 0.817; p<0.001).
DISCUSSION
While the concept that frailty results in adverse healthcare events in community dwelling older adults is well-established,19–20 the notion that frailty can forecast adverse post-operative events in older adults is relatively new. Using a frailty score to risk stratify surgical patients represents a paradigm shift from current pre-operative risk assessment strategy. Frailty measurements were collected by both pre-anesthesia nurse practitioners and a research assistant who were trained in a single 30-minute training session which included a description of the tests (e.g. how to perform the Mini-Cog) and then role playing actually performing the measurements. The current study found that accumulated frailty characteristics are related to a higher rate of hospital complications following major elective surgery in two surgical specialties. In patients who had four or more abnormal frailty characteristics (a group whom this study defined as frail), over half of patients in both the colorectal and cardiac surgery populations had one or more postoperative complications. Our analyses included controlling for increasing age in the relationship between frailty burden and the occurrence of one or more post-operative complications. In the cardiac group, complications significantly increased in a dose response fashion between all three frailty groups after controlling for age. In the colorectal group, complications were different between the non-frail and frail groups after controlling for age. ROC curves were superior to the null hypothesis and demonstrate the ability of increasing frailty deficits to forecast the occurrence of one or more complications in both surgical groups. Participants with a higher burden of frailty had longer length of stays and higher thirty-day readmission rates in both the cardiac and colorectal surgery groups.
A growing body of literature supports the concept that accumulated frailty deficits (a term used to describe an abnormal frailty characteristic) are related to adverse post-operative outcomes in older adults.10–12, 21–25 In addition to our reports, there are five published studies on this topic.
Dasgupta and colleagues21 studied 125 patients 70 years and older undergoing elective operations (mostly orthopedic) prospectively. The Edmonton Frail Scale was used to define frailty which sums domains such as function, cognition, nutrition, geriatric syndromes and health status.26 Frailty was defined as an Edmonton Frail Scale score of > 7. Frail individuals were more likely to have post-operative complications (Odds Ratio 5.2) and a reduced chance of being discharged to home (p=0.02). The authors concluded that frailty assessment refines risk assessment of older adults undergoing elective operations.
Kristjansson and colleagues24 studied 178 patients 70 years and older undergoing elective operations for colorectal cancer prospectively. Baseline “comprehensive geriatric assessment” was performed which assessed and summed the geriatric domains of function, burden of co-morbidity, cognition, nutrition and mood. Patients were defined as fit, intermediate or frail. Frail individuals were more likely to have a severe post-operative complication or death (62%) in comparison to fit (33%) or intermediate (36%) individuals (p=0.002). The authors concluded that frail patients have significantly increased risk for severe post-operative complications following colorectal resection.
Makary and colleagues23 studied 594 patients 65 years and older who presented to pre-anesthesia clinic for a variety of operations prospectively. This study is notable because it is the only information relating “phenotypic frailty”20 to surgical outcomes. Phenotypic frailty was defined using the five criteria of weight loss (shrinking), decreased grip strength, exhaustion, low activity and slow walking speed. Frailty groups were assigned based on the number of accumulated abnormal characteristics. Results found that frailty was related to increased postoperative complications, longer length of stay and increased likelihood of disposition to an institutional care facility. The authors concluded that frailty can help patients and their physicians make more informed decisions.
Lee and colleagues22 studied 3,826 patients of all ages who underwent cardiac operations recorded in the Maritime Heart Center Cardiac Surgery Registry retrospectively. Frailty was defined as having one or more of three frailty deficits: dependence in one or more activity of daily living, use of a walking aid and/or a documented history of dementia. Results found frailty to independently predict hospital mortality, institutional discharge and mid-term mortality (up to three years). The authors concluded that frailty improves risk assessment prior to cardiac operations.
Saxton and Velanovich25 studied 226 patients of all ages undergoing a variety of general surgery operations retrospectively. Medical records were reviewed to create the 70 item Canadian Study of Health and Aging Frailty Index score which includes the domains of function, cognition, geriatric syndromes, co-morbidity burden, nutrition and mood.19 The patients who had post-operative complications had a higher median frailty index (p=0.007). The authors concluded that assessing pre-operative frailty may improve patient selection for operations.
The main reason this study is important is that it recognizes the ability of similar frailty characteristics to predict adverse post-operative events not only across operations, but across surgical specialties. At first, this concept seems intuitive because frailty represents decreased global physiologic reserves and is not limited to measuring compromise in a single organ system. However, ultimately, the ability of one simple frailty score to predict adverse post-operative outcomes across surgical specialties has powerful potential to unify how older adults are risk stratified prior to major operations in any specialty.
There are three main limitations of this study. First, the majority of participants in this study are male. This factor precludes accounted for any gender differences in the relationship of frailty and post-operative complications. Our study reflects the demographics of a Veteran’s Affairs patient population and not selection bias. Second, this study defines frailty as an accumulation of abnormal geriatric assessment domains which is one of two current (and contesting) strategies to define frailty. This study did not use the definition of phenotypic frailty which is accepted by gerontologists.20, 23 Third, the history of whether or not a patient had fallen in the six-months prior to their operation was always taken from the patient. While this provides a uniform methodology to collect the data, this strategy did not account for potential differences between a falls history provided by a caregiver which might differ from the history provided by the patient.
In conclusion, accumulated frailty characteristics in the domains of function, cognition, chronic disease burden, walking speed, nutrition and geriatric syndromes predict the occurrence of one or more post-operative complications across surgical specialties. This knowledge can aid clinicians in pre-operative counseling and surgical decision-making for older adults undergoing major operations. Future directions of this work are to compile the data on frailty and postoperative outcomes from the multiple single center studies currently published with the goal of designing multi-institutional clinical trials to standardize a pre-operative frailty evaluation. This accomplishment has the potential to improve the care of all older adults who are considering whether to undergo a major operation.
Acknowledgments
Financial Support: Paul B. Beeson Award – NIA K23AG034632 (TNR); Dennis W. Jahnigen Award - American Geriatrics Society (TNR); NIH K24-HL-089223 (MM).
Footnotes
Oral Presentation as Scientific Paper at the American College of Surgeons, October 26, 2011.
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