{
  "abstract": "Prehabilitation transforms the preoperative waiting period into an opportunity for patients to actively improve their health before surgery. With surgical populations ageing and presenting with increasing frailty, patient prioritised outcomes, such as postoperative complications and disability, affect >20% of patients undergoing major surgery, resulting in substantial healthcare costs. This review combines the current evidence for prehabilitation components, including exercise, and respiratory, nutritional, cognitive, and psychosocial interventions. Although respiratory prehabilitation showed high certainty evidence for reducing postoperative pulmonary complications after major surgery, other components showed promising but lower certainty benefits. Multimodal prehabilitation, especially when exercise and nutrition are combined, seems to be most effective for improving clinical and patient centred outcomes. Significant knowledge gaps remain, however, about optimal programme design, delivery models, target populations, and strategies to maximise adherence. Patient perspectives emphasise the importance of individualised coaching or support from healthcare professionals, or both, home based accessibility, and collaborative care. Future research should include a focus on pragmatic multicentre trials with robust cost effectiveness analyses to support implementation in the health system of effective, scalable prehabilitation programmes that can meaningfully improve outcomes for surgical patients. Opportunities to enhance the effectiveness and reach of prehabilitation include exploiting existing and emerging technologies, as well as optimising participant support to maximise adherence.",
  "authors": [
    {
      "affiliations": [
        "Departments of Anesthesiology and Pain Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, ON, Canada",
        "Ottawa Hospital Research Institute, Ottawa, ON, Canada"
      ],
      "name": "Daniel I McIsaac"
    },
    {
      "affiliations": [
        "Departments of Anesthesiology and Pain Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, ON, Canada",
        "Ottawa Hospital Research Institute, Ottawa, ON, Canada"
      ],
      "name": "Leandra Amado"
    },
    {
      "affiliations": [
        "Ottawa Hospital Research Institute, Ottawa, ON, Canada"
      ],
      "name": "Gurlavine Kidd"
    },
    {
      "affiliations": [
        "Ottawa Hospital Research Institute, Ottawa, ON, Canada"
      ],
      "name": "Christopher Wanczycki"
    },
    {
      "affiliations": [
        "School of Health Science, University of Tasmania, Hobart, TS, Australia",
        "Department of Physiotherapy, Launceston General Hospital, Launceston, TS, Australia"
      ],
      "name": "Ianthe Boden"
    },
    {
      "affiliations": [
        "Departments of Anesthesiology and Pain Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, ON, Canada",
        "Ottawa Hospital Research Institute, Ottawa, ON, Canada"
      ],
      "name": "Emily Hladkowicz"
    },
    {
      "affiliations": [
        "School of Human Nutrition, McGill University, Montreal, QC, Canada",
        "Departments of Surgery and Anesthesia, McGill University, Montreal, QC, Canada"
      ],
      "name": "Chelsia Gillis"
    }
  ],
  "full_text": "Introduction The number of surgical procedures conducted worldwide is increasing, with 200-300 million people undergoing surgery each year. 1 The characteristics of people having surgery are also changing. Surgical patients are increasingly older, present with a greater comorbidity burden, and often have frailty, a multidimensional loss of reserve leading to poor tolerance of stressors.2–5 Although postoperative mortality is relatively rare (<3% at 30 days, even for older patients with frailty),5 6 other adverse patient prioritised outcomes are relatively common. For example, >20% of patients have a postoperative medical or surgical complication (eg, cardiac, pulmonary, and infectious adverse events) and a similar number report a clinically meaningful increase in disability after major inpatient surgery.7–10 These adverse patient outcomes result in increased use of healthcare resources. A moderate severity complication can result in an increase in perioperative costs of care of >US$20 000 (£15 100; €17 200),11 12 whereas a clinically meaningful increase in disability is associated with >C$8000 (£4281; €4940; US$5666) in attributable health system costs, independent of out-of-pocket costs incurred by patients.13 The incidence of adverse postoperative outcomes and associated healthcare costs are strongly related to a patient's preoperative health status.14 15Most major surgeries are conducted on a planned (also referred to as elective) basis, meaning that opportunities exist to improve patients' health status before surgery, which can enhance recovery and improve postoperative outcomes. Wait times for planned surgery vary widely across countries and indications, but are typically 4-6 weeks from diagnosis to surgery (depending on disease type and characteristics).16–18 This time allows the waiting period before surgery to be intentionally used to build reserve across multiple domains with the process of prehabilitation, reflecting the new approach of viewing the preoperative phase as a preparation period.19In this review, we look at the current state of prehabilitation science and practice, as well as explore the necessary steps to deliver effective prehabilitation before planned surgery at a health system level. We will share patient perspectives on successful prehabilitation design and participation, discuss the conceptual basis and evidence supporting individual components of prehabilitation (exercise, respiratory, nutritional, cognitive, and psychosocial prehabilitation), along with multimodal programming, and analyse new and future directions of prehabilitation research and practice as well as highlight key knowledge gaps preventing delivery of widespread effective prehabilitation.Prehabilitation Multiple definitions of prehabilitation have been proposed, but most share several common features. 20–23 Prehabilitation is typically characterised as an intervention that is used before surgery, involving activities with the intent of building or enhancing reserve and functional capacity in one or more domains (eg, exercise, targeted conditioning, nutrition, cognition, and psychosocial), and aiming to improve outcomes after surgery.Although core elements are shared across definitions, some key aspects of prehabilitation are unresolved. These aspects are whether prehabilitation includes medical optimisation, management of drug treatments, procedure specific education, with or without single risk factor management (eg, anaemia treatment with iron), or whether these interventions, along with prehabilitation, are more appropriately considered as complementary processes under a common overall process of preoperative optimisation. How some prehabilitation components are defined is also uncertain. For example, whether respiratory prehabilitation, which incorporates inspiratory muscle training and other approaches to building respiratory reserve, represents a subcomponent of exercise prehabilitation or a unique component has yet to be defined.24 The length of the programme required to differentiate prehabilitation from related but distinct perioperative interventions, such as Enhanced Recovery After Surgery (which often include, for example, carbohydrate supplementation and other components that begin in the immediate preoperative period), is also uncertain, with seven days before surgery currently suggested as a differentiating threshold.20 25 Ultimately, interventions undertaken for a meaningful portion of the preoperative waiting period that aim to build reserve and improve outcomes can be considered prehabilitation.Prehabilitation aims to support and engage patients to improve their health status before surgery. Not surprisingly, prehabilitation is prioritised by patients and the public, along with clinicians and health system leaders.26–28 Therefore, understanding the composition of prehabilitation programmes, along with their component interventions, is key to advancing prehabilitation research and practice. Current evidence mainly focuses on exercise (about 70% of available trials) and nutritional (about 35% of available trials) components, whereas psychological and cognitive components are less well studied.20 25 Programmes that combine components (ie, multimodal prehabilitation) are emerging as some of the most promising approaches to prehabilitation.A variety of approaches to programme design and delivery also exist within and across each component. Effective prehabilitation relies on patients' capabilities as well as their engagement and commitment to prehabilitation, highlighting the importance of patient oriented programme design and evaluation.29 30 Equally important is grounding interventions in programme theory (ie, a logic model to describe the pathway through which an intervention is understood to have its effect), which provides a structured framework to clarify mechanisms of action, guide implementation, and ensure that outcomes are meaningfully linked to intervention components.31 Because prehabilitation requires adequate time to engage in the intervention and build reserve, prehabilitation programmes are mainly limited to patients preparing for planned (elective) surgeries.Sources and selection criteria As a narrative clinically focused review, sources were not identified through systematic literature searches. For each topic discussed, however, we focused on describing results from recent, high quality systematic reviews that included only randomised controlled trials. Where such reviews were not available, we included recent high quality reviews of randomised trials and observational studies. Where systematic reviews were not available, we described findings from individual randomised trials, as applicable. Different approaches to prehabilitation may carry differential importance for patients with different risk factor profiles, or having different surgery types. Because the available data did not suggest important effect modification by surgery type or patient characteristics, 25 32 we included all relevant evidence looking at adult patients having any type of planned surgery. Box 1 outlines patient perspectives on prehabilitation.Box 1Patient perspectives on prehabilitation “Prehabilitation is a collaborative process—something done with the patient, rather than to the patient.”Gurlavine (Gurlie) Kidd, prehabilitation patient research partnerPatient informed considerations for prehabilitation:Prehabilitation should be co-designed with patients and adapted to individual needs, capacities, and preferences.Engagement in prehabilitation requires behaviour change and can be challenging, particularly in the context of frailty, fatigue, and competing demands.Coaching and regular follow-up are key to supporting adherence, building confidence, and sustaining participation.Home based and flexible programme delivery can improve accessibility and integration into daily routines.Practical strategies (eg, goal setting, tracking, and scheduled check-ins) can support motivation and accountability.Prehabilitation may increase both physical capacity and psychological readiness for surgery, including a sense of control and confidence.Early integration into surgical care pathways supports uptake and reinforces prehabilitation as part of routine patient care.Prehabilitation components Exercise prehabilitation Cardiopulmonary fitness is a strong and consistent predictor of adverse outcomes after surgery. 9 33 Cardiac and pulmonary complications are the most common organ adverse events after surgery, and most strongly predict subsequent mortality and use of healthcare resources.34 For older adults, loss of lower limb strength and function are the largest contributors to disability after surgery.35 Hence exercise is a foundational component of prehabilitation, because exercise aims to build strength and cardiopulmonary reserve in advance of the substantial physiological stress of surgery. About 70% of prehabilitation programmes evaluated in randomised trials included an exercise component in isolation or as part of a multimodal programme.25 Although no optimal approach to exercise prehabilitation is defined, most programmes combined aerobic and strength training, occasionally incorporating functional exercises, such as stretching or balance, or both. Exercise is typically prescribed at moderate intensity (eg, aerobic exercise targeting moderate perceived exertion with a Borg scale,36 although high intensity interval training techniques are emerging as an effective approach).25 37 In a systematic review and network meta-analysis that included 133 randomised controlled trials with an exercise prehabilitation component, isolated exercise prehabilitation reduced postoperative complications (odds ratio 0.50, 95% confidence interval (CI) 0.39 to 0.64) and length of hospital stay (−0.93 days, 95% CI −1.27 to −0.58), while improving health related quality of life (equivalent to 2.3 points on the Short Form-36 Physical Component Score, 95% CI 1.0 to 3.6) and physical recovery (equivalent to 25.7 m on the six minute walk test, 95% CI 6.1 to 45.4).25 Although effect estimates were consistent with clinically meaningful benefits for each outcome, the certainty of benefit was low to very low because the included randomised controlled trials often had a high risk of bias and estimates were imprecise with moderate to high heterogeneity.Because evidence supporting the benefits of exercise prehabilitation is promising but of low certainty, understanding the specific types of programmes, how the programmes are delivered, and what constitutes optimal dose and duration for different patient subgroups are important questions. Studies comparing moderate intensity exercise prehabilitation with high intensity interval training are generally lacking. One systematic review and meta-analysis of 12 studies (n=832) that combined randomised and prospective observational studies comparing high intensity interval training with standard care reported a significant reduction in postoperative complications (odds ratio 0.44, 95% CI 0.32 to 0.60); this effect estimate was similar in direction and magnitude to estimates derived from reviews that pooled all types of exercise interventions.37 In a systematic review and meta-regression to identify programme features associated with greater prehabilitation efficacy across 98 randomised controlled trials (n=8222), increased programme duration or session frequency did not increase the benefits of exercise prehabilitation.32 This review also found no evidence that supervised (v self-directed) or facility (v home based) programmes increased the efficacy of prehabilitation, but caution is needed in evaluating these results because reporting of prehabilitation interventions is often limited in quality and veracity.38Currently, exemplar randomised trials without major risks of bias, that are adequately powered for clinically relevant outcomes, and that show significant improvements in postoperative complications and patient oriented recovery, typically involve more than four weeks of prehabilitation. Prehabilitation should be conducted multiple times each week at moderate intensity, with programmes personalised by an exercise professional to target strength and cardiovascular fitness, performed with at least partial supervision at a facility or with a combined home based and facility based design.39–42 Table 1 provides descriptions of exercise prehabilitation intervention designs consistent with the available best evidence. Table 2 has an evidence summary for the different prehabilitation interventions. Exercise programmes will often need to be individualised, especially when participants present with physical limitations (eg, musculoskeletal injuries or pain). How such programmes can be effectively funded and delivered at a health system level is an important knowledge gap.43Table 1Descriptions of prehabilitation approaches consistent with best available evidenceComponentFrequencyIntensityTimeTypeEnact and extentResponseRiskStaff and resourcesDifficulty of each sessionDuration of each sessionMode of sessionMinimum start time before surgery and length of programmeTailoring and progressionPotential to harm/injury patientExercise Strength2-3 per week2 sets30 minInterval3-6 weeksIncrease resistance 1-2kg every 2-3 sessionLowExercise professional60-75% 1RMMajor muscle groupsSupervised sessions with home programmeFree or fixed weights Aerobic2-3 per weekModerate to high30 minContinuous/3-6 weeksIncrease work rate to maintain target RPE 5-8LowExercise professional50-90% VO2 maxIntervalSupervised sessions with home programmeLarge muscle groupsErgometer, treadmillRespiratory IMT7 per weekModerate to high10-20 minInitial face to face then home based training1-6 weeksIncrease intensity 2cm H2O every 2-3 daysNegligiblePhysiotherapist or respiratory therapist30-70% MIPHandheld device Preop educationOnceLow20 minFace to face1 day to 4 weeksNot requiredNegligiblePhysiotherapist or respiratory therapistNutrition UniversalOnceProvision of structured nutritional recommendations30 minGroup (virtual or in person)7 daysNANegligibleNutrition training Targeted to malnutrition riskTwice up to once per weekProvision of targeted nutritional recommendations and personalised program of nutritional supplementation60 minInitial face to face then follow-up phone call/virtual7-30 days, depending on severity of malnutrition riskMonitor weight, resolution of nutrition impact symptoms, and potentially body composition and functionLowRegistered dietitian or registered nutritionistOral nutrition supplements, protein supplements, and/or vitamins/minerals (as needed), rarely parenteral nutritionCognitive5 per week; greatest efficacy if ≥150 minutes per weekNA30-60 minIdeally home based with virtual supervisionUncertainty remains: thought to be at least 10 hours of trainingBrain training difficulty should adapt to performanceNegligiblePrehabilitation coach; potential involvement of neuropsychologistInternet connected devicePsychosocialUncertainty remains: ranges from one-off information sessions to dailyNAUncertainty remains: ranges from 30 min (motivational interviewing/brief psychoeducation) to 60 min (cognitive behavioural therapy)Individual or (support) groups; face-to-face or virtualNeeds based (varies widely)NANegligiblePsychologist; licensed counsellor; potential involvement of social workerInternet connected device (if required for virtual or app based therapy)MIP, maximum inspiratory pressure; NA, not available; RM, repetition maximum; RPE, rating of perceived exertion; VO2max, maximum oxygen consumption.Table 2Evidence summary for different prehabilitation interventionsPrehabilitation componentPopulation and contextMain findingsStrength of evidenceKey limitationsKey knowledge gapsExerciseMixed surgical populations↓ Complications (odds ratio ~0.50); ↓ length of hospital stay (~1 day); ↑ functional capacity; ↑ health related quality of lifeLow-very lowHigh risk of bias; heterogeneity; imprecision; poor reportingOptimal dose and intensity; programme design; target populations; scalable deliveryRespiratoryCardiac, thoracic, and abdominal surgery↓ Postoperative pulmonary complications (relative risk ~0.4-0.6); ↑ inspiratory strength; ↓ length of hospital stayModerate-high (cardiothoracic); low-moderate (abdominal)Variation in trial quality; less certainty in abdominal surgeryEffectiveness in other populations; optimal delivery; role of education v inspiratory muscle trainingNutritionMixed and gastrointestinal surgical populations; strongest in populations that are malnourished↓ Complications (~30%); ↓ infections; improved body compositionLow-moderateSmall trials; heterogeneous interventionsTarget populations; optimal type and dose; integration with exerciseCognitiveOlder adults; cardiac and non-cardiac surgeryPossible ↓ delirium; improved cognition; mixed resultsVery lowSmall trials; low adherence; feasibility concernsOptimal dose; adherence strategies; scalable deliveryPsychosocialMixed surgical populations↓ Length of hospital stay; ↓ pain; mixed effects on anxiety and depressionLow-moderateHeterogeneous interventions; unclear active componentsOptimal components; scalable interventions; guideline developmentMultimodalMixed populationsMost likely to improve outcomes; ↑ recovery; ↑ health related quality of lifeLowImprecision; risk of bias; unclear synergy between componentsOptimal combinations; tailoring; cost effectivenessRespiratory prehabilitation Respiratory prehabilitation is a form of targeted conditioning that specifically aims to minimise postoperative pulmonary complications, such as pneumonia. 44 Compared with cardiac complications, postoperative pulmonary complications are more common, are twice as costly for hospitals to manage, and have similar effects on patient morbidity and mortality.45 Most postoperative pulmonary complications develop within the first two postoperative days, and the first 24 hours is a critical window to reverse atelectasis and prevent microbial airway contamination.46Pathophysiological effects on the respiratory system during major non-orthopaedic surgery reduced respiratory muscle strength by 20-50% and half of all patients had immediate postoperative atelectasis.47–49 The mechanical disadvantage of weaker respiratory muscles being less likely to reverse closed lung tissue can be compounded by a patient's lack of awareness on how to perform effective deep breathing exercises immediately after surgery. Respiratory prehabilitation deals with these concerns through preoperative inspiratory muscle training to optimise respiratory muscle strength, as well as by educating patients to develop the skills to perform lung expansion exercises as soon as they awake from surgery.44 A meta-analysis of 64 randomised controlled trials investigating prophylactic physiotherapy interventions aimed at preventing postoperative pulmonary complications after abdominal surgery suggested that respiratory prehabilitation may be comparatively more effective in preventing postoperative pulmonary complications (nine trials, n=1226; relative risk 0.43, 95% CI 0.29 to 0.55) than postoperative phase interventions, including chest physiotherapy (seven trials, n=453; relative risk 0.92, 0.58 to 1.48), incentive spirometry (five trials, n=512; relative risk 0.90, 0.43 to 1.88), or early mobilisation (five trials, n=596; relative risk 1.01, 0.69 to 1.48).50Seven systematic reviews with meta-analyses have estimated the pooled effect of inspiratory muscle training before major visceral surgery from at least 18 randomised controlled trials.44 Despite varying methodological quality of both the source trials and the reviews themselves, the positive effects of preoperative inspiratory muscle training have been reported consistently, with increases in inspiratory muscle strength of at least 15%,51 reductions in relative postoperative pulmonary complication risk by 6-61% (relative risk 0.61, 95% CI 0.39 to 0.94),52 and shorter hospital stay by 1-2 days.53 Combining inspiratory muscle training with whole body exercise training improved the certainty of the risk reduction in postoperative pulmonary complications (relative risk 0.43, 0.31 to 0.60).52 Specific to cardiothoracic surgery, a strong and consistent independent effect of preoperative inspiratory muscle training reducing postoperative pulmonary complications was found, with a risk reduction of at least 15% after thoracic (relative risk 0.44, 0.23 to 0.84) and cardiac (relative risk 0.57, 0.50 to 0.81) surgery, with time sequential meta-analyses suggesting no further trials are required.52 53 Subgroup analysis suggested that inspiratory muscle training may be equally effective across age groups and risk categories,53 although the evidence for inspiratory muscle training in preventing postoperative pulmonary complication for abdominal surgery is less certain (relative risk 1.07, 0.78 to 1.46).50Inspiratory muscle training involves a spring loaded or electronic device to generate a load during inspiration (figure 1). One baseline assessment of a patient's maximum inspiratory pressure is required followed by individualised prescription of a training programme at 30-70% of their maximal load performed for 15-30 min daily, either at home or with in-person supervision. To maintain an effective training load, tailored dose progression is needed with weekly supervision by telephone or telehealth. Inspiratory muscle training is effective as little as a week before surgery.53 54 Even with improved inspiratory muscle strength, however, patients must also consciously perform repeated large volume breaths to sustainably reverse atelectasis after surgery. Specifically, effective respiratory prehabilitation not only involves increasing respiratory muscle strength before surgery, but also educating and training patients to start deep breathing exercises immediately on awaking from surgery.Figure 1Example of an inspiratory muscle training device (electronic flow resistance device; Powerbreathe)The independent effect of preoperative education and training in breathing exercises starting on awaking from anaesthesia has been tested in an international multicentre clinical trial that included 441 participants having all types of patients awaiting major abdominal surgery.55 Preoperative education and training on how to perform volume recruitment breathing exercises specifically designed to overcome atelectasis enables patients to start these self-directed exercises on awaking from surgery (figure 2). An individual participant meta-analysis of two large randomised trials (n=800) in abdominal surgery estimated that preoperative education plus preoperative respiratory muscle training halved the risk of postoperative pulmonary complications (adjusted odds ratio 0.53, 95% CI 0.34 to 0.85) with a number to treat of eight, and shortened length of hospital stay.54 56 This treatment effect seemed to be consistent across patient subgroups, including age, surgery type, and those with or without existing respiratory disease. Within the public Australian and New Zealand hospital system, preoperative education and training in breathing exercises saved A$8 (£4.2; €4.9; US$5.6) in downstream hospital costs for every A$1 invested,57 suggesting that this equipment free, single face-to-face session delivered up to a day before surgery by a trained physiotherapist is among the most cost effective prehabilitation interventions.58 Whether alternative modes (ie, telehealth or multimedia) or delivered by other health professionals are equally effective is not known. Table 1 provides descriptions of respiratory prehabilitation intervention designs consistent with available best evidence, supported by an evidence summary in table 2.Figure 2Breathing exercises to prevent pneumonia after surgeryNutritional prehabilitation About one in three patients present to surgery with a potentially modifiable preoperative nutrition related risk factor (eg, malnutrition or abnormalities in skeletal muscle quantity or composition) that increases the risk of postoperative morbidity. 59 Malnutrition, characterised by inadequate nutritional intake leading to loss of body mass and function, is especially amenable to short term intervention and should therefore be prioritised in prehabilitation care.60Although the preoperative window is often short, nutritional status can be meaningfully improved before surgery. In a small pragmatic randomised trial (n=110) of multimodal prehabilitation, including protein supplementation and expert nutritional advice, patients with colorectal disease increased their dietary protein intake over a mean of 18 days, reducing the proportion failing to meet recommended protein targets (≥1.2 g/kg/day) from two thirds to one third (prevalence ratio 0.59, 95% CI 0.36 to 0.82).61 A secondary analysis of five prehabilitation trials (pooled n=266) grouped by nutritional status showed that 4-6 weeks of multimodal prehabilitation improved preoperative weight, body composition, and functional capacity, highlighting the potential for nutritional optimisation in patients who are moderately malnourished awaiting surgery.62Preoperative nutrition interventions can improve surgical outcomes. A network meta-analysis of 186 randomised trials in mixed populations (n=15,684) identified that preoperative nutrition interventions (in isolation or when combined with exercise) reduced postoperative complications by about 30% (the certainty of the evidence ranged from very low to moderate).25 These data from randomised controlled trials are consistent with real world observational data, where a cross sectional study of 27 tertiary centres (n=200) in Australia found that patients with upper gastrointestinal cancer who received three or more dietetic consultations in the month before surgery had less preoperative weight loss than those who received fewer consultations (1.2 (2.0) v 3.1 (3.3) kg, P=0.001). Among patients who were malnourished, having ≥3 dietetic consultations was independently associated with a reduction in surgical complications (odds ratio 0.2, 95% CI 0.1 to 0.9).63 Similarly, in a randomised trial (n=101) that exclusively enrolled patients with colorectal cancer with preoperative weight loss, oral nutrition supplementation combined with dietary advice resulted in fewer infections (odds ratio 0.3, 95% CI 0.1 to 0.9) and mitigated further postoperative weight loss compared with dietary advice alone.64These clinical findings may, in part, be explained by improvements in immune function. Malnutrition is consistently associated with an impaired immune response.65 66 For example, a small study (n=69) of patients admitted to hospital with malnutrition found that complex I activity, a key step in mitochondrial energy production, in peripheral blood mononuclear cells was significantly lower than in age matched controls (P<0.001). After four weeks of nutritional support (including oral nutritional supplements, or enteral or parenteral feeding), peripheral blood mononuclear cell complex I activity was restored to levels comparable with those of healthy volunteers.67 Given the substantial energy demands of initiating an immune response for postoperative wound healing, restoring immune cell mitochondrial function through nutritional intervention may help to explain the observed reduction in complications in patients who are malnourished.Despite these promising findings, uncertainty remains about the optimal approach. A recent Cochrane systematic review of 16 randomised trials (n=2164) could not determine, because of very low quality evidence, whether preoperative parenteral nutrition, enteral nutrition, immune enhancing formulas, or standard oral supplements have a definitive effect on clinical outcomes for patients with gastrointestinal disease. Subgroup analyses by nutritional status, however, suggested that standard oral nutrition supplements probably reduced infectious complications in patients who were malnourished (relative risk 0.6, 95% CI 0.4 to 0.9), reinforcing the importance of targeted interventions.68 A risk stratified approach that prioritises specialist resources for patients who are malnourished, while providing education on nutrition through web based tools, booklets, or surgery schools for patients who are not malnourished, is likely an effective and resource efficient strategy.61 69As well as considerations of malnutrition and related deficits in muscle quality and quantity, patients with class 3 obesity (eg, body mass index >40) have an increased risk of adverse postoperative outcomes. Limited evidence exists, however, about the effectiveness of intentional weight loss interventions delivered within a prehabilitation framework in non-bariatric surgical populations.70 Preoperative weight management in bariatric surgery represents a distinct clinical context, with its own evidence base and considerations.71 72Overall, the evidence base for nutritional prehabilitation is limited by small sample sizes, heterogeneous interventions, and low certainty of effect estimates. Important uncertainties persist about who to target beyond malnutrition (eg, poor diet quality), the optimal strategy, dose, and duration of preoperative nutrition interventions, and the timing and type of exercise appropriate for patients with different nutritional statuses across surgical populations. Table 1 provides descriptions of nutritional prehabilitation intervention designs consistent with available best evidence, supported by an evidence summary in table 2. Although mechanistic studies suggest plausible pathways, these findings are preliminary. Collectively, these limitations highlight the need for large, rigorously designed, risk stratified trials to determine which patients benefit most and how nutrition should be optimally integrated with other components of multimodal prehabilitation.Cognitive prehabilitation Cognitive prehabilitation by multidimensional structured brain training is an emerging component of prehabilitation that aims to enhance brain function and reserve before surgery to decrease the incidence and severity of postoperative neurocognitive disorders, a collective term comprising postoperative delirium and longer term cognitive decline diagnosed up to a year after surgery. 73 As the surgical population ages rapidly, developing interventions to decrease postoperative neurocognitive disorders is crucial, because postoperative delirium is one of the most common complications in older surgical patients (incidence 15-53%),74 is associated with poor long term physical and cognitive recovery,75 and results in substantial increases in use of health system resources,76–79 along with substantial distress for patients and families.80Although multiple approaches to increasing cognitive reserve are described,81–87 accumulating evidence suggests that cognitive prehabilitation may improve cognitive recovery after surgery. So far, most cognitive prehabilitation trials have used home based88–92 electronic (computer or tablet based) interventions88–93 that dynamically target multiple cognitive domains by increasing task difficulty as performance improves. The available evidence is early stage and of low certainty, however, because multiple evidence gaps have yet to be considered.Multicentre randomised trials of cognitive prehabilitation are lacking. So far, only four single centre cognitive prehabilitation trials have been powered for cognitive outcomes89 91 93 94 (the remainder have been feasibility designs).88 90 92 In a randomised trial of 80 participants from Spain (intermediate risk and non-cardiac surgery), the cognitive training group had a significant improvement in postoperative memory (8%; P<0.05) and Mini-Cog scores (20%; P=0.03).91 In a Chinese randomised trial comprising 208 patients undergoing cardiac surgery, who were in hospital for their prehabilitation, the cognitive training group had a significant decrease in the incidence of postoperative delirium (odds ratio 0.43, 95% CI 0.23 to 0.77; P=0.007), severe delirium (odds ratio 0.46, 0.25 to 0.82; P=0.01), median duration of delirium (P=0.008), and number of delirium positive days (P=0.007).93 Another randomised trial from China (n=141; gastrointestinal surgery) found a significant decrease in long term neurocognitive disorders (15.9% in the cognitive training group v 36.1% in the control group; P=0.05).94 Finally, a randomised trial of 268 participants from the US (in older patients undergoing non-cardiac surgery) reported a 9% absolute decrease in delirium, but this result was not significant (P=0.08). In post hoc analyses limited to adherent participants only, and accounting for frailty characteristics, delirium was significantly reduced (P=0.04).89Table 1 provides descriptions of cognitive prehabilitation intervention designs consistent with available best evidence, but the data are preliminary given the development stage in this area. Table 2 gives an evidence summary. Few participants (range 9-40%)88–90 92 in existing trials achieved adequate intervention adherence unless participants were in hospital for prehabilitation,93 or were provided with constant support.91 Barriers to adherence included feeling overwhelmed, information technology problems, and the required time commitment.88 90 The optimal dose, duration, and delivery system for cognitive prehabilitation are not known. Optimisation of the design of future cognitive prehabilitation programmes will be required and could involve structured coaching and real time technology support to optimise adherence to the interventions, ensuring adequate time is available before surgery to complete cognitive training tasks, and inclusion of participants with pre-existing cognitive impairment or frailty, or both.Psychosocial prehabilitation The mind-body connection has received increased attention in the perioperative context. Systematic reviews 95–97 have evaluated the effect of various psychological factors on physiological surgical outcomes. Postoperative pain is predicted by anxiety, depression, and catastrophising,98–102 and pain perception is further amplified by negative emotions such as anger and sadness.103 104 Stress directly impairs wound healing105–107 and disrupts the gut microbiome108; indirectly, health damaging behaviours may be concomitantly adopted.109Preoperative psychological preparation includes the provision of procedural and sensory information, behavioural instruction, cognitive interventions (reducing negative thoughts), emotion focused interventions (managing feelings), relaxation, and hypnosis. In various combinations, these approaches have improved postoperative outcomes.110 111 A component network meta-analysis (35 trials) identified reduced length of stay (−0.5 days, 95% credible interval (CrI) −0.9 to −0.2) and less postoperative pain (−0.15 standardised units, 95% CrI −0.27 to −0.016) for any psychological intervention versus control. For length of stay, all components (other than emotion focused interventions) contributed to this effect. Combining provision of procedural information, sensory information, and either behavioural instruction (mean difference −0.96, 95% CrI −1.62 to −0.35) or relaxation (mean difference −1.02, −2.00 to −0.052), reduced length of stay by about one day each. Relaxation was the most effective component for reducing postoperative pain (−0.28 standardised units, 95% CrI −0.49 to −0.058). The evidence was insufficient, however, that any particular component contributed to a decrease in anxiety or depression.112 Overall, although the results seem promising for a variety of components of psychosocial prehabilitation (table 1 provides brief descriptions of psychosocial prehabilitation intervention designs consistent with available best evidence, supported by an evidence summary in table 2), the specialty consistently identifies the need for more generalisable randomised trials to inform detailed recommendations, including practice guidelines.112–114Multimodal prehabilitation Although accumulating evidence supports the individual prehabilitation components already discussed, a systematic review with network meta-analysis that included 186 randomised controlled trials (n=15,684) suggested that multimodal prehabilitation interventions are most likely to improve critical outcomes. 25 In estimating the relative efficacy of individual components and multimodal approaches compared with standard care, multimodal prehabilitation interventions were ranked as the approaches with the highest probability of improving three of four critical outcomes assessed in the review, based on P scores (P scores ranged from 0 to 1, with values closer to 1 representing greater probability of being the most efficacious intervention).115 For length of hospital stay, exercise with psychosocial prehabilitation was most likely to be efficacious (P score=0.97), whereas for physical recovery and health related quality of life, exercise with nutrition, and exercise with nutrition and psychosocial prehabilitation, ranked highest (P scores=0.72 and 0.85, respectively).25 Two patient centred outcomes were clinically and significantly improved with a combination of exercise, nutrition, and psychosocial prehabilitation, including physical recovery (43 m on the six minute walk test, 95% CI 6 to 81) and health related quality of life (3.5 points on the Short Form-36 Physical Component Score, 95% CI 0.8 to 6.1). Similar results were reported in a systematic review and network meta-analysis of 25 trials restricted to abdominal surgeries, where aerobic exercise with inspiratory muscle training was the most likely approach to reduce the risk of pneumonia (odds ratio 0.21, 95% CI 0.04 to 1.15; P score=0.91), the second most likely approach to decrease rates of overall morbidity and mortality (odds ratio 0.66, 0.28 to 1.26; P score=0.68), and had the largest pooled effect size for reducing length of stay (mean difference −1.7 days, −2.1 to −1.3).24The certainty of benefit from multimodal prehabilitation in abdominal surgery and in other surgical specialties is low because current estimates are imprecise and underlying trials are at risk of numerous biases.24 25 Also, despite clinician and patient perspectives that complementary prehabilitation components (eg, exercise with nutrition) may be synergistic (rather than additive) in improving outcomes after surgery, based on the notion that increasing functional reserve requires both physiological stimulus and adequate substrate,116 current evidence from a component network meta-analysis of randomised trials does not suggest strong synergy between different prehabilitation components.25 This lack of evidence for synergy suggests that the high probability of efficacy for multicomponent interventions likely reflects the additive benefits of different prehabilitation components that aim to deal with unique and overlapping deficits before surgery.Adherence The causal pathway from provision of an efficacious prehabilitation programme to effectively improving outcomes at a population level requires achieving adequate levels of adherence to prehabilitation programmes. Available studies suggest that high levels (>75%) of adherence can often be achieved, but most data come from small, single centre studies that provided facility based programmes (limiting access) or resource intensive strategies to enhance programme adherence (limiting adoption), or both. 30 Therefore, results from idealised studies may not be generalisable as prehabilitation is implemented more broadly. Although systematic reviews of home based programmes, which are prioritised by patients, suggest efficacy, pooled effect sizes were smaller for home based programmes than for predominantly facility based programmes.25 117 For subgroups such as older patients with frailty, who may benefit substantially from prehabilitation,118 low programme adherence is consistently reported in randomised trials.119–121 In the PREPARE (Preoperative Exercise to decrease Postoperative Complication Rates and Disability Scores) trial, a multicentre randomised trial that exclusively enrolled 847 older patients with frailty, no significant or clinically meaningful improvement in patient reported disability was seen across all participants. In analyses limited to participants achieving >75% adherence, however, a significant and clinically meaningful (mean difference −5 points, P=0.03) improvement was reported for participants receiving prehabilitation relative to usual care.121Important questions need to be answered about what types of patients can effectively receive prehabilitation at home (which could optimise access) versus those who would benefit from facility based programmes and supervision (which could optimise effectiveness for those who can attend), or a hybrid approach. Insights into these important questions should begin to emerge from individual participant data meta-analysis of multicentre trials that are starting to appear in the literature.42 122 123 Also, both framework guided qualitative research based on validated behaviour change theories and patient or caregiver led inductive exploration of new insights, should be pursued to help develop and refine interventions that improve adherence, while also informing patient centred programme design globally.29 124Implementation Moving from current prehabilitation evidence, which is predominantly early stage and derived from single centre trials, towards routine delivery of effective prehabilitation at a health system level, will likely need to follow an established framework for implementing health promoting interventions, such as the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. The RE-AIM framework is an iterative approach to evaluating and implementing complex health interventions that aligns with the multilevel structure of prehabilitation. 125 Specifically, successful prehabilitation requires both activation and behavioural change at the patient level, and appropriate structural design and support at the system level. Also, a deeper understanding of the optimal balance between the potentially greater efficacy of supervised, facility based prehabilitation compared with less costly and more scalable home based programmes must be established.Although evidence certainty seems to support implementation of respiratory prehabilitation in patients undergoing cardiothoracic surgery, achieving high certainty evidence for other surgery types, and other prehabilitation modalities, will require future randomised trials that look at the limitations of the current evidence base. Key areas for researchers should include a focus on multicentre trial design (including pragmatic features126 to support generalisability), concurrent qualitative evaluation of barriers to participation and implementation based on SWAT (study within a trial) designs,127 and design and execution of trials with a low risk of bias. Also, robust, preplanned cost effectiveness analyses would help to inform the economic rationale for implementation of prehabilitation.As a multicomponent intervention, future directions in intervention development are also required to support implementation of effective and feasible programmes. Improved reporting quality of prehabilitation studies, and in particular randomised trials, will be required to support meaningful implementation.38 128 For exercise, understanding whether high intensity interval training approaches can more efficiently prepare some patient subgroups for surgery than traditional moderate intensity programmes represents a crucial next step for patients facing wait time sensitive surgeries. For nutritional prehabilitation, understanding the role and relative efficacy of different approaches (eg, advice or counselling v explicit supplementation) remains to be determined. Moreover, whether nutritional restoration should precede or coincide with exercise training is unclear, particularly in patients with limited metabolic reserve where correcting nutritional deficits may be necessary to enable effective physical adaptation.62 Cognitive prehabilitation interventions require early stage research to show that adequate intervention participation can be feasibly achieved, whereas psychosocial interventions that aim to enhance resilience (positive adaptation despite adversity)129 might support more effective patient centred recovery after surgery. Overall, understanding what interventions should be prioritised for what types of patients having what types of surgery would likely optimise clinical and cost effectiveness, but could create barriers to programme design and implementation based on complexity.Future directions As a multicomponent intervention, supported by a multidisciplinary specialty that requires engagement and support from patients, clinicians, researchers, and health system leaders, future directions in prehabilitation are likely to span a wide and diverse spectrum. Currently, few guidelines deal with prehabilitation in clinical care ( table 3), but increasing evidence of the efficacy of prehabilitation is likely to increase inclusion of prehabilitation in guidelines moving forward. From the perspective of patients, clinicians, and health system leaders interested in offering prehabilitation services broadly to patients preparing for surgery, several important barriers and knowledge gaps remain before achieving a high level of certainty that most aspects of prehabilitation can be effectively delivered in real world settings (figure 3).Table 3Clinical guidelines related to prehabilitationOrganisationPopulationRecommendationStrengthEvidence qualityNational Institute for Health and Care Excellence 2020136Adults undergoing primary hip or knee replacementProvide advice on preoperative rehabilitation, including exercises and lifestyle or wellbeing guidanceNot formally graded (implied recommendation)Low to moderateEuropean Society for Clinical Nutrition and Metabolism 2025137Patients with severe malnutrition or high metabolic risk, or both, shall receive nutritional treatment preoperativelyProvide 10-14 days of nutritional treatment before surgeryPrehabilitation shall be offered on a risk stratified basisStrong (both)HighEnhanced Recovery After Surgery Society and European Society of Thoracic Surgeons 2019138Patients undergoing lung surgery with borderline lung function or exercise capacityConsider prehabilitation; provide nutritional support if malnourishedStrong (both)Low (prehabilitation); moderate (nutrition)Enhanced Recovery After Surgery Society for oesophageal surgery 2021139Patients undergoing oesophagectomyRecommend nutritional support if malnourished; recommend multimodal prehabilitationStrong (nutrition); moderate (prehabilitation)Low (both)Centre for Perioperative Care 2023140Older adults with frailtySuggest considering referral for prehabilitationNot specifiedNot specifiedAmerican Society of Anesthesiologists 2025141Older adults undergoing inpatient surgeryNo recommendation due to insufficient evidenceNot applicableNot applicableMacMillan Cancer Support 2025142OncologyRisk stratified prehabilitation delivered at escalating intensity as universal, targeted, or specialist interventions based on baseline evaluationNot formally gradedNot specifiedEnhanced Recovery After Surgery Society for elective colorectal surgery 2025143Patients undergoing elective colorectal surgeryNo specific prehabilitation regimen can be recommended before surgeryNo specific recommendationLowFigure 3Key areas of focus in advancing prehabilitation towards routine effective delivery at the system, programme, and patient levelsTechnology Wearable technology and virtual programme delivery are emerging as promising modalities to improve the efficacy and safety of prehabilitation, especially in the home based setting. 130 For virtually delivered home based programmes, wearable vital signs and motion sensors could help to monitor programme adherence and performance. Although the human relationship between a coach or healthcare professional, or both, and participant is an important facilitator of adherence,29 the influence of human factors, including training and provider type, on the effectiveness of prehabilitation is not known. Understanding these relationships could identify opportunities for machine learning and large language models to rapidly evaluate data and provide feedback, to alert coaches or healthcare professionals, or both, to participation deficits and to increase effective human led support strategies at scale. Also, large language models could be trained to act as coaching agents, providing an easily accessible guide for participants, which could allow effective human coaches to support a larger number of participants. Although the data suggest that prehabilitation is safe at home, even for older patients with frailty,131 remote monitoring could provide extra safety in monitoring for adverse events, such as falls, dysrhythmias, or other physiological disturbances.Using technology with integrated wearables could also help to facilitate application of behavioural economic techniques to increase participation and adherence levels. Current evidence from systematic reviews suggests that behavioural incentives, such as contracts and lotteries, can increase participation in exercise and other health promoting activities,132 133 and therefore these approaches should be considered for prehabilitation. Although the effect sizes for behavioural interventions are typically moderate in scale (about a 1.5-fold relative increase in target behaviours), existing data suggest that these interventions are often cost effective.133 134 Therefore, researchers should collaborate with patients to develop and evaluate behavioural incentive programmes specifically tailored to prehabilitation.Target populations Identifying optimal target populations is a major gap for most components of prehabilitation. Although high certainty data support respiratory prehabilitation for patients undergoing cardiothoracic surgery, and nutritional prehabilitation for patients who are malnourished, optimal target populations for exercise, cognitive, and psychosocial prehabilitation, as well as further target populations for respiratory and nutritional prehabilitation, have yet to be identified. Identifying target populations will require a complimentary approach of using validated and feasible screening tools to recognise populations expected to benefit, followed by testing targeted prehabilitation interventions in trials limited to specific populations. Also, biomarker profiles and responses show promise in guiding prehabilitation efficacy and explaining underlying mechanisms. 135 More generalisable trials inclusive of a variety of subgroups should be conducted. Synthesis of postulated effect modifiers based on advanced techniques, such as individual participant meta-analyses, will also be required, facilitated by structured data sharing between research teams. Establishing and analysing high quality registries with common data elements linked to implementation programmes could further enhance our understanding of target populations based on real world data, ideally sourced from a variety of countries and health systems.Conclusions Improving health status and building reserve before surgery through prehabilitation is prioritised by patients and clinicians, and supported by promising evidence. Patients should be encouraged to improve their health promoting behaviours before surgery, with support from their clinicians. For patients undergoing major surgery, systematic application of preoperative respiratory prehabilitation based on surgery specific modalities should be pursued. For other forms of prehabilitation, accumulating evidence of efficacy combined with consistent safety signals suggest that individual patients may benefit from exercise and nutritional prehabilitation, alone or in combination, if high levels of adherence can be achieved. For health system leaders, before widescale adoption, research supporting the real world effectiveness (ie, consistent with real world care based on feasible and scalable approaches) of exercise and nutritional prehabilitation has yet to be produced. Researchers and health system leaders should prioritise efforts that will bring effective prehabilitation closer to routine effective implementation. For cognitive and psychosocial prehabilitation, further foundational evidence is required.Questions for future research What patient populations are most likely to benefit from what types of prehabilitation interventions?What is the minimum effective dose (duration and intensity) of prehabilitation required to meaningfully improve outcomes after surgery?How can existing and emerging technologies be leveraged to increase the clinical and cost effectiveness of prehabilitation?Can prehabilitation programmes effectively improve patient level or system level outcomes, or both, in real world settings?Patient involvement Two patient partners (CW and GK) were engaged immediately after our team received a request to produce this review. In partnership, the team decided that an explicit section on patient perspectives would be the optimal approach, with GK and CW further involved as full authors to review the proposed outline as well as the final paper in its entirety.",
  "title": "Prehabilitation in preparation for surgery",
  "uid": "78cb06c6-0d05-5bcb-a02d-5bfcfba4120b"
}