Prehabilitation: Impact on Postoperative Outcomes

Major surgical interventions, particularly for intra-cavity cancer resections, impose significant physiological and psychological stress on patients. Postoperative complications are common, occurring in 15% to 40% of major (inpatient) surgeries, and are associated with prolonged hospital stays,1 increased health care costs,2 and reduced postoperative survival3 as well as delayed adjuvant therapy for cancer.4 The likelihood of experiencing postoperative complications is linked to several factors: the nature, extent, and duration of the surgical insult; the physiological and psychological resilience of the patient; and the care administered before, during, and after surgery (Fig. 1). It is increasingly clear that, given sufficient time and resources, interventions before surgery can augment both physical and psychological resilience.FIGURE 1: The perioperative pathway integrating prehabilitation, comorbidity optimization, and shared decision-making.Prehabilitation is a multimodal intervention before surgery that aims to optimize functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes, and facilitate recovery. Prehabilitation involves screening, needs-based assessment, and the individualized prescription of one or more of exercise, nutrition, and psychological interventions supported by behavior change techniques.5 The concept of prehabilitation has evolved from unimodal approaches focused principally on physical exercise training or nutrition to comprehensive multimodal strategies addressing multiple risk factors and supported by behavior change interventions.6 While all patients may benefit, to varying degrees, from prehabilitation interventions, individualizing therapy maximizes service efficiency and cost-effectiveness.7 Prehabilitation, as defined above, should be differentiated from the management of long-term conditions, commonly referred to as comorbidity/multimorbidity management, before surgery, which typically requires modification of pharmacological interventions under specialist guidance (eg, anemia, diabetes, COPD). Prehabilitation and comorbidity management are complementary, probably synergistic, and should occur in parallel, but are distinct interventions. The notion of reframing “waiting lists” as “preparation lists” has highlighted the opportunities available when preoperative patient evaluation takes place early in the surgical journey, ideally as close as possible to the “moment of contemplation of surgery.” Early screening enables the identification of modifiable behavioral and comorbidity risk factors and preliminary triage of the patient’s prehabilitation needs and their perioperative risks. This, in turn, facilitates (i) shared decision-making; (ii) comorbidity management; and (iii) prehabilitation. Patients identified as at increased risk during screening undergo targeted assessments, which inform individualized domain-specific (eg, exercise, nutrition, psychology) prescription of needs-based interventions (Fig. 1). This manuscript reviews the impact of prehabilitation on postoperative outcomes, including patient-centered, clinical, and cost-effectiveness measures, and the opportunities available for the implementation of prehabilitation into surgical pathways. DOMAINS OF PREHABILITATION Exercise Physical activity is defined as any and all bodily movements that require skeletal muscle contraction and energy expenditure. Exercise is a subset of physical activity that involves specifically planned, structured, and repetitive movements that aim to improve performance or physical fitness.8 Aerobic exercise training relies on increased oxygen delivery to fuel continuous and moderate-to-high-intensity dynamic activities, which involve large muscle groups such as running and cycling. It increases heart rate and energy expenditure. Regular aerobic exercise training improves cardiovascular system and skeletal muscle function which leads to increased aerobic exercise capacity (VO2peak; anaerobic threshold) and endurance performance.9 Resistance exercise involves moving against a resistance with the aim of increasing muscular strength, power, bulk, or endurance. This is achieved by varying the resistance, the number of repetitions of the exercise in a set, the number of sets, and the rest between sets.10 Reduced cardiorespiratory fitness and functional capacity are associated with adverse surgical outcomes.11,12 Surgical stress triggers an inflammatory response leading to metabolic dysregulation, muscle catabolism, and impaired wound healing.13 Prehabilitation enhances physiological reserve and thereby potentially reduces the incidence of postoperative complications.6,14 Studies have shown that preoperative exercise programs can improve oxygen uptake (VO2 max),15 enhance muscular strength,16 and facilitate early mobilization postoperatively.16 Assessment of functional capacity using a validated test before the commencement of a prehabilitation program allows the exercise program to be tailored to the patient. Cardiopulmonary exercise testing is the gold standard for assessing functional capacity and may also be used to optimize comorbidities (arrhythmia control, bronchospasm) and to prescribe exercise.17 Alternative simpler functional tests include the shuttle walking test, the sit-to-stand test, the timed up and go test (TUG), and the 6-minute walk test, although these may be less sensitive to changes in fitness and may have ceiling effects in healthy individuals.18 Exercise programs should be based on the patient's baseline fitness and prescribed and reported using the FITT principle.19 The FITT principle specifies the frequency (how often?), intensity (how hard?), time (how long?), and type (aerobic vs. resistance; intervals vs. continuous) of exercise. The prescription should also include instructions for progressing exercise intensity as fitness improves to maintain the training effect.10 Patients should be instructed to estimate the intensity of exercise using perceived exertion (eg, 10-point Borg Scale), the talk test, and/or heart rate zones (Table 1). TABLE 1 - Methods to Evaluate Exercise Intensity Evaluation method Low intensity Moderate intensity Vigorous intensity Borg Scale 0-10 rest—maximal 0-4Rest-moderate 5-7Somewhat hard-hard 8-10Very hard-maximal Talk test Speak comfortably Talk but can’t sing Few words only Breathing/speaking • Easy to breathe• Can carry on a conversation • Breathing more heavily• Can only complete 1-2 sentences • Breathing very hard• Can only say a few words Heart rate range <55% maximum heart rate 55%-75% maximum heart rate >75% maximum heart rate Example exercise Slow walk • Brisk walk• Cycle <10 miles/h• General gardening• Dancing • Running• Cycle >10 miles/h• Heavy gardening• Climbing stairs• Aerobic dancing Unfortunately, the reporting of exercise interventions in prehabilitation trials is suboptimal. In a recent scoping review of exercise interventions in prehabilitation randomized controlled trials, only 44% provided sufficient details to allow replication of interventions, including how and when they were administered and progressed, and only 15% reported who delivered/supervised the exercise program.20 This makes it challenging to reproduce an exercise intervention, compare interventions, or implement an intervention across a health system. The biological effects of different exercise intensities and modalities are different: the anti-inflammatory/immune modulating effect of high-intensity exercise is dissimilar to low intensity walking, and consequently, their clinical effects may not be the same, for example, tumor regression. All exercise may not therefore be equal, and it is critical that the type and exercise intervention are accurately prescribed and reported. Furthermore, only 45% of prehabilitation trials reported adherence to the exercise intervention. Failure of an exercise intervention may be because of a lack of efficacy of the exercise itself, but it also could be due to a failure of adherence because of the method of implementation. Thus, it is important to report not only the details of an exercise intervention but also how it was implemented. Adherence to an exercise program may also be impacted by the degree of supervision (reported adherence rates vary from 16% to 97%). A recent systematic review reported that the efficacy of exercise prehabilitation was greater in programs with more than 1 supervised exercise session a week.21 Supervision may be of particular importance for high-risk patients or frail patients who may lack the confidence to exercise alone. Early prehabilitation studies involved predominantly aerobic exercise interventions, given the reported increased risk of complications in patients with reduced aerobic exercise capacity.15,22 High-intensity interval programs (HIIT) were chosen primarily because interval programs improve fitness more quickly than moderate continuous exercise programs, time is limited in preoperative pathways, and they are more effective.23 Resistance exercise has increasingly been combined with aerobic exercise training in prehabilitation programs with the aims of improving muscle strength and mass, preventing sarcopenia, and ameliorating the effects of cancer cachexia.24,25 Combining aerobic and resistance exercise increases the intervention burden for patients, and further research is needed to evaluate the impact on surgical outcomes. There are no RCTs that compare aerobic versus resistance versus combined exercise. A recent systematic review of unimodal exercise prehabilitation concluded that prehabilitation reduced postoperative complications and length of stay. All 29 studies that included whole-body exercise included aerobic exercise; 13 studies included a combined program of aerobic exercise and resistance exercise.26 No studies evaluated resistance exercise alone. Further high-quality studies comparing resistance and aerobic exercise are needed to clarify the most effective type of exercise program for patients before surgery. Recent systematic reviews confirm that exercise interventions before surgery are acceptable to patients, feasible and safe.14,26 Increasing evidence suggests that exercise has antitumor and cancer preventive effects and that it may augment the efficacy of other neoadjuvant cancer treatments, including chemotherapy, radiotherapy, and immunotherapy.27 In colorectal cancer, tumor regression was increased 12-fold in patients participating in a supervised, personalized HIIT aerobic exercise program when compared with controls.28 This finding has subsequently been replicated with HIIT training in esophageal cancer29 and in prostate cancer.30 The mechanisms of action of exercise in prehabilitation have not been clarified, but proposed pathways include modulating tumor hypoxia, enhancing innate immunity, and modifying the inflammatory response.31 Further clinical trials are required to clarify the mechanism and explore the tumor regression effect of exercise in neoadjuvant therapies. Furthermore, there is an inverse dose-response relationship between exercise and long-term mortality after cancer treatment, emphasizing the importance of maintaining the changes in exercise behavior that prehabilitation programs initiate.32 Exercise interventions also have an important impact on mental health reducing both anxiety and depression which are prevalent in cancer surgery patients.33 This effect is mediated by exercise releasing endorphins and other neurotransmitters that enhance mood.33 In summary, exercise interventions before surgery improve surgical outcomes and enhance overall health and recovery and may improve quality of life. Further research should focus on the standardization of exercise interventions, defining the optimum type of exercise, exploring the mechanisms by which exercise impacts tumor regression, and exploring the effects of prehabilitation interventions on long-term exercise behavior and health outcomes. Nutrition Malnutrition is defined as a state resulting from a lack of intake or uptake of nutrition that leads to altered body composition and body cell mass and reduced function.34 Malnutrition is an established risk factor for poor surgical outcomes, including increased postoperative morbidity and mortality, and extended length of hospital stay.35,36 Malnutrition also impacts the costs of care with 30% to 50% higher hospitalization costs being incurred by malnourished compared with well-nourished patients.37 Malnutrition is particularly common in cancer surgical patients, with a prevalence between 20% and 70%.38 Malnutrition in cancer may be caused by reduced food intake secondary to nutritional impact symptoms (reduced appetite, disturbed GI function, pain, difficulties chewing or swallowing), which in turn may be caused by the tumor or the adverse effects of cancer treatment. Many surgical patients are also sarcopenic, defined as reduced skeletal muscle mass in association with reduced muscle strength and function. Sarcopenia may occur as a consequence of aging and the frailty phenotype39 or secondary to cancer-related cytokine-mediated inflammation and cancer cachexia40 and is associated with adverse outcomes after surgery. Nutritional prehabilitation aims to mitigate the impact of malnutrition. All surgical patients should be screened for malnutrition using a validated tool such as NRS-2002, Nutrition-Risk Screening Tool,41, PG-SGA, Patient-Generated Subjective Global Assessment,42 and MUST (Malnutrition Universal Screening Tool)43 (Table 2).46 Patients identified as at-risk should be formally assessed by a registered dietician or nutritionist using a validated nutritional assessment tool such as the Subjective Global Assessment (SGA), Patient-Generated-SGA (PG-SGA),44 or the GLIM.45 Body composition analysis using dual-energy x-ray absorptiometry (DXA), bio-electrical impedance analysis (BIA), CT, or MRI may be used to identify sarcopenia, although this remains primarily a research tool currently. Functional assessments include whole-body exercise tests and hand-grip strength using dynamometry. Dynanometry may be used to monitor response to interventions47 but its utility as a screening tool is less certain48 (Table 2). TABLE 2 - Nutritional Screening and Assessment Nutritional screening Nutritional assessment by dietician or nutritionist Nutritional assessment tools Physical assessment Body composition Functional assessment Validated tools• PG-SGA short form42• NRS-200241• MUST43 PG-SGA44Subjective global assessment• Weight loss• Metabolic demand• Physical exam• Functional status • Weight• Weight history• Anthropometry • CT• MRI• Bioimpedance • CPET• Hand grip• Shuttle walk• Timed up and go• 6-min walk test Components: Weight loss• >10% loss in 6 mo• 5% loss in 3 moBMI<18.5Reduced intake• (<50% of normal intake in last 7 d) GLIM45• Reduced food intake• Weight loss• Reduced muscle mass• Reduced body mass Nutritional interventions should be targeted to the patients’ needs. Universal nutritional interventions include dietary counseling that includes advice on healthy eating and protein intake (aiming for 1.5 g/kg) and strategies to cope with nutritional impact symptoms such as nausea, reduced taste, and reduced appetite (Table 3). Targeted interventions including oral nutritional supplements (ONS) are recommended if requirements are not being met with food. ONS should be considered in all malnourished patients if the window before surgery is short.49 Adherence to advice may be facilitated by dietary counseling and follow-up and behavioral change support.50 TABLE 3 - Nutritional Interventions, Indications, and Targets Intervention Indications Dietary advice • Aim for 25–30 kcal/kg per day• Aim for 1–1.5 g protein/kg (ideal body weight if BMI ≥30) per day• Food and increased if low to to nutritional for example, nutritional supplements • to requirements with food to protein requirements • ONS with and • No standardization of not may complications the of before major cancer surgery is A recent reported reduced postoperative morbidity and length of with oral nutritional supplements that are with and of nutritional that malnourished cancer patients major surgery should 7 to of ONS before surgery, although these supplements are not available in all health care are that effects to the when given in sufficient during the with the of their activity being in the are food as dietary that are not in the and the or activity of in the and are combined in a they are as in major surgery a in postoperative complications with the of and a lack of standardization of duration of treatment, or of they are not recommended interventions include nutrition and/or nutrition, which are recommended when a patient their nutritional requirements oral A recent systematic review of randomized controlled trials of nutritional prehabilitation and in multimodal prehabilitation programs concluded that it is associated with a in length of postoperative quality of quality of and mortality in major the quality of the studies was limited studies with high-quality trials with a intervention are needed to the of this effect and the optimum intervention. and patients for surgery is an of prehabilitation. Patients significant before surgery, and they may also This may be due to a recent cancer or from being by the and the of surgery. increases the risk of mortality in cancer across a of tumor and adherence to and postoperative and depression have been linked to prolonged hospital higher and increased A body of evidence suggests that prehabilitation programs psychological including interventions and can preoperative Prehabilitation interventions therapy and stress management have shown in improving patient high-quality trials psychological interventions or in multimodal prehabilitation pathways are have been included in multimodal prehabilitation trials, but their are not well which makes replication trials should focus on interventions and to identify the of psychological interventions. 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Validated tools should be used to identify modifiable risk factors and comorbidities that may be or impact perioperative risk (Fig. 2). 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