Outcomes after thoracic surgery are better predicted by preoperative evaluation of patients’ physiologic reserve (also known as personal biologic age rather than chronologic age), using validated assessment tools in multidisciplinary collaboration with geriatricians. Targetable risk factors should be identified, and methods should be utilized to minimize these risks. Prehabilitation has been validated as a tool to increase functional and nutritional status of patients undergoing surgery in other specialties and improve outcomes. Although research is still limited in thoracic surgery, early results are promising.
Physiologic age rather than chronologic age is a better predictor of outcomes after thoracic surgery.
Useful assessment tools exist to identify frailty in older patients, such as clinical frailty scales, frailty index, frail screening scale, and frailty phenotype, which may identify appropriate candidates for prehabilitation. Assessment is done best in a multidisciplinary fashion between primary care, geriatricians, and thoracic surgeons.
Preoperative exercise-based intervention (prehabilitation) has demonstrated reduction of morbidity and mortality in other surgeries but in thoracic surgery continues to be under discussion with heterogeneous but potentially promising results.
In thoracic surgery the 2 main groups of high-risk patients are young adults with comorbidities, mainly chronic lung and heart disease, and older adults, mainly with frailty. This review focuses on these 2 different populations and on strategies to define and better prepare them for surgery and thus improve postoperative outcomes.
Many older patients, defined as those patients 65 years or older, present an array of challenges when undergoing thoracic surgery. Although advances in minimally invasive techniques have made it feasible for the older population to undergo thoracic surgery safely, , elderly patients are more likely to have complications, have longer lengths of stay, , and are more likely to require involved discharge planning, including need for home health aides or formal rehabilitation.
Preoperative rehabiliation (prehabilitation) can optimize functional and nutritional capacity and serve as a teachable moment in which healthy lifestyle changes actively can be made. Prehabilitation has 2 parts: (1) the identification of preoperative conditions that are associated with postoperative morbidity and (2) an attempt to minimize these conditions preoperatively with the hope it will result in better outcomes. Furthermore, when looking at mortality after elective surgery, it frequently is characterized by multiorgan dysfunction. In fact, 1 study compared major surgery to running a marathon. Few adults can go out and run a marathon without training, but, after several months of regular training, some could complete this goal. Their bodies did not grow additional heart and lung tissue, but their organs became more efficient. This analogy is an attractive comparison, particularly to prehabilitation, because marathon training also has developed its own science. Prehabilitation tries to improve multiple organ systems prior to elective surgery.
History of Prehabilitation
Prehabilitation does not appear as a topic in the surgical textbooks of the 1980s. At that time, preoperative preparation for patients referred to immediate correction of blood volume, intravascular fluids, and electrolyte balance. There were no large databases. The under-appreciated personal computers became available in the 1990s. Surgical outcome reports were based on laborious chart reviews, usually from single institutions, and were prone to subtle selection biases of the lead surgeon. For elective cases, selection of patients was binary: either a patient was surgical candidate or not.
The Goldman criteria were published in 1977. This was a landmark prospective study of preoperative variables that predicted cardiac events after major noncardiac surgery in 1001 patients over age 40. Data were collected from Massachusetts General Hospital from October 1975 to April 1976. By multivariate discriminant analysis, the investigators were able to identify 9 predictors: preoperative third heart sound or jugular venous distention; myocardial infarction in the preceding 6 months; more than 5 premature ventricular contractions per minute before operation; rhythm other than sinus or premature atrial contractions on preoperative electrocardiogram; age over 70 years; intraperitoneal, intrathoracic or aortic operation; emergency operation; important valvular aortic stenosis; and poor general medical condition. Patients could be separated into 4 classes of significantly different risk. Ten of the 19 postoperative cardiac fatalities occurred in the 18 patients at highest risk. The investigators created a clinical prediction rule. Of the maximum 53 possible points, 23 were potentially controllable. The Goldman criteria became popular as a method to identify elevated risk for elective surgery and a way to reduce that risk with preoperative intervention or timing.
The gold standards to judge the success of an operation have been the 30-day mortality rate and the disease recurrence rate. With modern critical care, a low 30-day mortality rate may be a reflection of an advanced intensive care unit team. Today, it is recognized that the 90-day mortality frequently is much higher than the 30-day mortality. Even more ominous, a recent analysis shows that nursing home placement 1 year after surgery is a function of age. This is a poor outcome that was not measured 4 decades ago. Additionally, surgery for lung cancer can trigger a loss of independence that patients may deem unacceptable. ,
Neoadjuvant chemoradiation trials for esophageal and stage IIIA (N2) lung cancer , in the mid-1990s demonstrated to thoracic surgeons that dramatic but temporary declines in functional status might follow the neoadjuvant stage. The toxicity of combined chemoradiation frequently reduces the performance status of the patient temporarily. For some patients for whom the hope was to perform the surgical resection by 4 weeks after the neoadjuvant therapy, their frailty interfered with the plan. On later reassessment, the clinicians found that these same frail patients had improved their strength and functional status with an additional 2 weeks to 6 weeks of recovery time, thus making them strong enough for an operation. This experience taught a generation of thoracic surgeons that performance status could be improved prior to surgery.
Identification of Candidates for Prehabilitation
Often frailty is the metric utilized to identify those who may benefit from prehabilitation. Frailty is a syndrome of decreased reserve and resistance to stressors resulting from cumulative declines across multiple physiologic systems and causing vulnerability to adverse outcomes. Frailty, although more prevalent in older adults, is not limited to this population , and is important to recognize and quantify. The presence of frailty and degree of severity are known to be predictors of worse postoperative outcomes. , Therefore, it remains critical to identify high-risk surgical candidates and target modifiable risk factors (pulmonary and cardiac function; functional capacity; degree of lung resection; cognitive reserve and delirium risk; polypharmacy; and nutritional status) to improve postoperative outcomes.
It is accepted that operative risk is associated more closely with functional status, frailty, and physiologic age rather than chronologic age. High rates of frailty have been identified on a national level as present in 15.3% of patients greater than 65 years old, with notable variation by region, race/ethnicity, and income. In thoracic surgery, preoperative patients appear to have even higher rates, with estimate prevalence of frailty and prefrailty as high as 68.8% of older patients.
The thoracic surgery patient routinely suffers from multiple comorbidities in addition to higher rates of frailty. These may have an impact on their surgical outcomes. Outcomes also may be impacted by higher rates of chronic obstructive pulmonary disease (COPD) and decreased pulmonary reserve, including physiologic changes of the respiratory system. These changes include but are not limited to reduced chest wall compliance, reduction of elastic recoil, and decreased alveolar gas exchange, resulting in decreased P o 2 and forced expiratory volume in the first second of expiration (FEV 1 ). In addition, there are higher rates of malnutrition and sarcopenia in esophageal cancer patients related to their prevalence of smoking and ethanol use. All these factors are associated with worse postoperative morbidity and mortality in thoracic surgery. ,
Assessment of frailty in addition to routine preoperative work-up includes validated metrics, such as clinical frailty scale ( Fig. 1 ), frailty phenotype, and the more detailed frailty index. , Higher frailty index has been associated with increased 30-day complications, failure to wean from ventilator, reintubation, surgical site infection, pneumonia, and grade 4 complications after lobectomy. , These tools are important in identifying frail older adults, thus introducing an opportunity to increase functional and nutritional reserves to decrease the decline in the postoperative period.
In addition to traditional preoperative work-up, consisting of laboratory tests, and imaging such as echocardiogram or stress tests, high-risk patients may be identified with frailty scales, geriatric assessment, performance of physical examination, and physiologic testing. Physical examination should be directed for signs of COPD, pulmonary hypertension, arthritis, kyphosis, and hiatal hernias. Standard physiologic tests include pulmonary function testing, 6-minute walk tests (6MWTs), and exercise-induced hypoxia testing. Absolute step count recently has been noted to be not predictive of postoperative outcome. These previously listed assessment practices are aligned with the recently published recommendations from the American College of Surgeons and the American Geriatrics Society. At minimum, the team should evaluate in the preoperative period the following domains to identify high-risk vulnerable patients: those with impaired cognition, delirium risk, impaired functional status, impaired mobility, malnutrition, difficulty swallowing, and in need of a palliative care assessment. Ways to assess and address frailty as well as screen for cognitive impairment (eg, mini-cognitive test) among older adults who are candidates for surgical interventions have been published by the Society of Perioperative Assessment and Quality Improvement and include the different methods available and how to best utilize them in the perioperative period ( Fig. 2 ). ,
Modern-day Evidence for Prehabilitation
Use of prehabilitation originated outside of thoracic surgery. In cardiac surgery, prehabilitation was shown to reduce hospital length of stay. After major abdominal surgery, patients who underwent formal prehabilitation prior to colectomy had fewer complications and an average savings of $21,946 per patient. This has been similarly validated for pulmonary rehabilitation and inspiratory muscle training to prevent atelectasis. For example, after cardiac surgery, in a single-blind randomized trial by Hulzebos and colleagues, those who underwent preoperative inspiratory muscle training had reduced odds of postoperative pulmonary complications (odds ratio [OR] 0.52; 95% CI, 0.30–0.92), pneumonia (OR 0.40%; 95% CI, 0.19–0.84), and shorter length of stay (LOS) (median 7 days vs 8 days, respectively; P = .02). No outcome change, however, was shown for simple preoperative information booklet and diaries without physical intervention.
Within the realm of thoracic surgery, data and randomized controlled trials (RCTs) are more limited, with only circumstantial benefit in thoracic patients.
In patients undergoing lung resection for lung cancer, the few RCTs that exist had small sample sizes, with heterogeneous interventions ranging from strength training to inspiratory muscle training. One RCT looked at a multimodal prehabilitation program on perioperative functional capacity in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non–small cell lung cancer. Their study found that a 14-day intervention increased the preoperative 6MWT and postoperative forced vital capacity (FVC) but did not show an improvement in clinical outcomes, such as LOS and complications. Another study showed only circumstantial benefit in thoracic patients (weak recommendation), noting in their review that most previous studies lacked statistical power to demonstrate an effect on postoperative complication for thoracic surgery. A recent systematic review of lung resection showed, however, intervention-based improvement in walking endurance, peak exercise capacity, dyspnea, risk of hospitalization, and postoperative pulmonary complications when there was a minimum of 1 week to 4 weeks with 1 session to 3 sessions per week at moderate intensity (50% of endurance capacity). Pulmonary rehabilitation is recommended by professional societies for high-risk patients. Finally, most prior studies on prehabilitation largely looked at older patients or frail patients. There is, however, limited evidence to suggest younger patients may achieve similar benefits from pulmonary rehabilitation.
In esophageal cancer there is an even higher burden of care due to neoadjuvant chemoradiation in most cases followed by esophagectomy (a highly morbid procedure in many cases). , There also is a high prevalence of declined nutritional status due to the nature of this disease with weeks of dysphagia. On the other hand, this conveys a unique opportunity to prepare patients, especially older adults, for this complicated procedure. Prehabilitation that includes exercise and nutritional intervention was shown in 1 recent RCT to improve functional capacity (study primary endpoints included walk distance, 6MWT, and proportion of patients who experienced a change in functional capacity) before and after esophagectomy. The RCT unfortunately was not powered enough to show any differences in their secondary outcomes (number and severity of complications, length of hospital stay, and readmission rates). In another study on prehabilitation by Soares and colleagues, pulmonary function and physical performance were improved before and after upper abdominal surgery. Although there are some data showing that prehabilitation can improve outcomes in esophageal cancer, the overall benefits, including postoperative complications and oncology outcomes, are yet to be determined and remain an active area of research.
Another issue surrounding prehabilitation of thoracic surgery relates to the time commitment. Although in other fields, such as cardiac surgery, it may be appropriate to wait 6 weeks prior to surgery, this is not practical in lung cancer patients, who may benefit from timelier oncologic resection. In this regard, only 2 RCTs looked at short-term (1 week or less) high-intensity rehabilitation in thoracic patients. One RCT found decreased LOS and complications in elderly thoracic patients undergoing a 7-day intensive prehabilitation program, and the other noted no difference but with premature study closure due to poor recruitment. New RCTs in other surgical subspecialties investigating prehabilitation or exercise intervention are actively enrolling, including the PERFORM-TAVR study ( NCT03522454 ), the PREHAB study ( NCT02219815 ), and the PREQUEL trial. The authors have identified no new RCTs in thoracic surgery, however, to investigate physical interventions, although there has been new interest in possible use of pedometer tracking as a possible tool.
The authors’ practice has synthesized the data, discussed previously, and developed their own best practice recommendations. The first step in their practice is to identify nonmodifiable variables (age, gender, stage, and family history) and, more importantly, modifiable variables (pulmonary and cardiac function, exercise capacity, amount of lung to be removed, polypharmacy, nutrition, and sleep) in a multidisciplinary office visit in conjunction with a geriatrician in older candidates. The steps in the authors’ preoperative evaluation are listed. A flowchart for the work-up (see Fig. 3 ) and the authors’ previously published minimum requirement functional cutoffs to consider candidacy for lung resection by degree of resection in older patients from their practice are provided in Table 1 , which includes adjunct tests cutoffs, such as oxygen consumption, should initial tests be abnormal, to stratify surgical candidacy better; the authors offer surgery based on the lowest category a patients falls into based on cutoffs provided.
Obtain complete history and physical examination, including body mass index
Obtain basic preoperative laboratory tests, imaging (at minimum, chest computed tomography and almost universal use of a PET scan).
Cardiac risk assessment (American Heart Association and American College of Cardiology) provides easily accessible practice guidelines for need for electrocardiography, echocardiography, or stress test.
Pulmonary assessment for lung resection patients includes pulmonary function tests (PFTs), including FEV 1 , measurement of diffusing capacity of the lungs for carbon monoxide (DLCO), and room air arterial blood gas.
Maximum oxygen consumption (V o 2max) , predicted postoperative lung function, and ventilation/perfusion scans may be used as adjuncts in setting of abnormal values to evaluate patients with marginal function.
In older patients, include comprehensive geriatric assessment.
Use of clinical frailty scale (score 1–9), identification of frailty phenotype (prefrail if 1–2 factors met or frail if 3 or more criteria met, including unintentional weight loss, self-exhaustion, slow gait speed, low energy expenditure, and weak grip strength), or frailty index (individual deficits/number of measured deficits)
Assess functional status, including activities of daily living and instruments of daily living
Performance status (Karnofsky Performance Status, Eastern Cooperative Oncology Group performance status)
Exercise tolerance tests: stair climbing, 6MWT, and most importantly walking distance
Measure of cognition and mood: Mini-Mental Status Examination, Geriatric Depression Scale, cognition and risk of postoperative confusion scale
Social support: quality of life after surgery, new supports needed, possible loss of independence, and goals of care, including advance planning and code status
Tobacco and alcohol abstinence for 7 days prior to surgery
Reduction in polypharmacy. Identify medications at risk of delirium (benzodiazepines and anticholinergics) and renal failure as well as develop β-blockade protocol, and discuss anticoagulation.
Sleep: recommend 6 hours to 8 hours of sleep per 24-hour period
Diet: calorie counts and quality of diet, possible nutrition laboratory tests
Recommend exercise 3 times a week for 1 hour. Reevaluate at 2-week mark if considering surgery with endpoints (kept appointment, exercised, and made objective improvement).
Use this time to adjust nutrition, sleep, and mood.
Consider adjunct use of pedometers to measure walk distance.
Surgical planning and hospital course
Reassess surgical candidacy at regular intervals.
If having surgery, develop intrahospital plan (minimize high risk medication, develop sleep regimens, discuss postoperative fluid management, utilizie nonpharmacologic prevention and management of delirium, establish early recovery after surgery protcols and utilizie in-hospital geriatrician comangement or consultation).