Prehabilitation in Clinical Practice: A Review of Concepts and Implementation in Enhancing Post- operative Outcomes

Anchala Jirakulsawat, BN.S.1, Nisa Noocharoen, BN.S.1, Pawit Somnuke, M.D., Ph.D.2

1Division of Operating Nursing, Golden Jubilee Medical Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Nakhon Pathom 73170, Thailand, 2Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

INTRODUCTION

In the midst of globalization and the expanding global population, particularly in the context of an aging demographic, the demand for healthcare, including hospitalization, has surged.1,2 This increase is further accompanied by the prevalence of non-communicable diseases, emerging conditions, and chronic comorbidities, necessitating both medical and surgical interventions. To address these challenges, evidence-based guidelines for intraoperative and immediate postoperative care have been established. These guidelines aim to facilitate rapid recovery and mitigate postoperative complications, such as prolonged hospital stays, hospital readmissions, escalated healthcare costs, and elevated mortality rates.3-5

Optimizing perioperative care necessitates a multidisciplinary approach that integrates surgical and anesthesia standpoints. Comprehensive medical management spans from preoperative assessment through to patient discharge. However, the pivotal factor determining favorable postoperative outcomes lies in the patient’s preoperative functional capacity. Limited functional capacity has been consistently linked to increased risks of 30-day mortality and postoperative complications. Consequently, various strategies have been devised to enhance and optimize preoperative functional status, particularly among vulnerable populations such as the elderly, frail individuals, and those suffering from malnutrition.4,6,7 The preoperative phase is widely acknowledged as a

Corresponding author: Pawit Somnuke E-mail: Pawit-pup@hotmail.com

Received 23 May 2024 Revised 28 June 2024 Accepted 28 June 2024 ORCID ID:http://orcid.org/0000-0002-6773-1882 https://doi.org/10.33192/smj.v76i9.269392

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

critical window for risk assessment, optimization, and meticulous patient preparation in anticipation of the physiological stress induced by surgical procedures.8

This review article underscores the significance of prehabilitation as a strategy for enhancing preoperative functional capacity by strengthening physiological and metabolic reserves in at-risk patients. It advocates for the integration of prehabilitation into routine anesthesia practice, emphasizing its potential benefits. The article also explores how prehabilitation can be integrated with Enhanced Recovery After Surgery (ERAS) within a framework of multidisciplinary collaboration, and introduces its implementation among various groups of specific patients.

Definition of prehabilitation

Prehabilitation, a term first proposed approximately two decades ago by Topp et al., pertains to a program aimed at enhancing functional capacity prior to admission to the intensive care unit (ICU).9 Despite its original conceptualization, prehabilitation has undergone a paradigm shift, and is now viewed as a valuable strategic approach during preoperative preparation to mitigate surgery-induced stress.10 The fundamental objective of prehabilitation is to minimize the risk of postoperative complications and expedite recovery through the proactive implementation of physical training, nutritional enhancement, and mental support, with the aim of reducing morbidity and mortality following surgery.

Optimizing the preoperative patient status necessitates a multidisciplinary collaboration involving perioperative clinicians, surgeons, anesthesiologists, geriatricians, nurses, physiotherapists, nutritionists, and various other pertinent healthcare professionals. This endeavor is often referred to as “pre-surgical conditioning”, representing measures aimed at enhancing the functional and mental status of patients before surgery, improving disease manifestations, and preventing potential adverse events through the adoption of prehabilitation principles.11

Implementation of preoperative prehabilitation approaches

The effectiveness of treatment extends beyond the surgical procedure alone; it also relies on the speed of recovery and the restoration of pre-surgery functional capacities. Implementing carefully planned physical activity programs, initiated 4-6 weeks before scheduled surgery, has been shown to enhance fitness levels.12 Additionally, as previously mentioned, integrating nutritional interventions, psychological support, and cessation of smoking and alcohol consumption is imperative and

should be incorporated into the multimodal prehabilitation regimen.

Physical exercises

One of the core components of prehabilitation is physical exercise, which encompasses a variety of activities proven to enhance functional capacity. These include aerobic exercise, resistance training, muscle strengthening, balance training, and flexibility exercises. The design of physical exercise programs is tailored to align with patients’ baseline physical abilities, as assessed by measures such as the 6-minute walk test (6MWT), oxygen consumption in the aerobic threshold (AT), and peak exercise capacity (VO2 max).11 Typically, the

recommended total exercise duration is 2.5 hours per

week, consisting of 2-3 sessions of 30-40 minutes of aerobic exercise per week. The target heart rate for each exercise session should range between 50-80% of the maximum age-related heart rate, calculated as 220 minus the individual’s age in years. Strengthening exercises targeting daily-life muscles are recommended twice a week, alternating with sessions of flexibility and balance exercises.4,13 To tailor an appropriate exercise program for each individual, common assessments of preoperative functional capacity14-31 are conducted as outlined in Table 1.

Nutritional optimization

The concept of nutrition in prehabilitation extends beyond merely replenishing deficit calories. Nutritional support is envisioned proactively, encompassing both the preoperative and postoperative periods.32 It is recommended that all patients, especially those with malnutrition and those undergoing gastrointestinal or cancer surgery, be encouraged to receive nutritional support. Enteral nutrition is prioritized for patients scheduled for major surgical interventions, with an intake of 1.2-1.5 g/kg of body weight of protein for approximately 7-14 days. Protein supplementation is suggested within 1 hour following physical activity to optimize muscle protein synthesis. Consumption of 140 g of carbohydrates around 3 hours prior to exercise is encouraged to enhance muscle and liver glycogen storage.33-36

Psychological wellness

Mental health holds equal significance to physical well- being, particularly in the context of surgery. Preoperative stressors such as fear, anger, depression, and anxiety, if left unaddressed, can accumulate and negatively impact recovery, treatment outcomes, and overall quality of life. Various strategies are proposed to alleviate psychological

TABLE 1. Preoperative functional capacity assessments14-31

Cardiopulmonary Exercise The gold standard for measuring functional The scoring system ranges from 0 to 20,

Testing (CPET)14-18 capacity and the capability to achieve where scores of 0-5 indicate normal metabolic demands. reference levels, while scores > 5

Requires significant time and resources. signify escalating risk factors. These Involves estimating cardiopulmonary function include: a ratio between pulmonary

and cellular respiration by assessing ventilation and CO2 production (VE/VCO2) physiological responses to exercise and slope of ≥ 34 = 7 points; heart rate cardiorespiratory performance. recovery (HRR) of ≤ 16 beats/min

Includes the monitoring of electrocardiogram = 5 points; O2 uptake efficiency slope (EKG), minute ventilation, heart rate, O2 (OUES) of ≤ 1.4 = 3 points; end tidal uptake, and CO2 output. CO2 partial pressure (PETCO2) of < 33 =

3 points; and peak O2 consumption (VO2

max) of ≤ 14 ml/kg/min = 2 points.

Peak VO2 < 15 ml/kg/min corresponds to metabolic equivalents (METS) < 4, resulting in postoperative complications.

Peak VO2 > 20 ml/kg/min indicates a low risk of postoperative mortality.

The Duke Activity Status

Index (DASI)14,19-21

Utilization of a 12-item questionnaire to DASI > 34 indicates a predicted VO2 determine the capacity of physical tasks max > 15 ml/kg/min.

performance. DASI < 34 is associated with an increased DASI score spans from 0 to 58.2 and risk of 30-day mortality or experiencing

possesses predictive capability for moderate to severe postoperative estimating the VO2 max as expressed complications among patients vulnerable to by the formula: VO2 max = (0.43 x DASI myocardial infarction or undergoing

score) + 0.96. major surgery.

DASI < 31.95 signifies low functional capacity among patients with preexisting stroke.

The level of O2 uptake at which lactate begins to increase in the circulation (anaerobic threshold, AT) < 9-11 ml/kg/min is related to postoperative complications and mortality.

The 6-minute walk test A sub-maximal exercise assessment The 6MWT values of 427 m and 563 m (6MWT)14,22-24 wherein a patient walks back and forth indicate a low AT of < 11 ml/kg/min and

on a level surface between 2 designated a high AT of > 11 ml/kg/min, respectively. markers. A 6MWT result of < 350 m is associated

The final walking distance is reported in with an increased risk of 12-month meters (m). disability following surgery.

A 6MWT result of 400 m corresponds to New York Heart Association (NYHA) classification 2.

TABLE 1. Preoperative functional capacity assessments14-31 (Continue)

measurement.

The final walking distance is reported in meters (m).

High-sensitivity cardiac The preoperative level of plasma hs-cTnT A cutoff of ≥ 14 pg/ml designates an troponin T (hs-cTnT)29,30 can aid in predicting peri-operative abnormal level of hs-cTnT, which predicts

Growth differentiation

factor-15 (GDF-15)29,31

The preoperative plasma level of GDF-15 can predict the risk of myocardial injury after non-cardiac surgery and also enhance cardiac risk evaluation by 30% compared to the Revised Cardiac Risk

Index (RCRI) alone.

The risk of myocardial injury after non-cardiac surgery is 12% when the GDF-15 level is between 1,000-1,500 pg/ml, and 34%

when > 3,000 pg/ml.

myocardial injury/infarction. perioperative coronary artery adverse events.

Abbreviations: 6MWT: The 6-minute walk test; AT: Anaerobic threshold; BNP: Brain natriuretic peptide; CO2: Carbon dioxide; CPET: Cardiopulmonary exercise testing; DASI: The Duke Activity Status Index; EKG: Electrocardiogram; GDF-15: Growth differentiation factor-15; hs-cTnT: High-sensitivity cardiac troponin T; ISWT: The incremental shuttle walk test; kg: Kilogram; m: Meter; METS: Metabolic equivalents; min: Minute; ml: Milliliter; NT-pro BNP: N-terminal pro-brain natriuretic peptide; NYHA: New York Heart Association; O2: Oxygen; OUES: Oxygen uptake efficiency slope; PETCO2: End tidal carbon dioxide partial pressure; pg: Picogram; RCRI: Revised Cardiac Risk Index; VCO2: Carbon dioxide production; VE: Pulmonary ventilation

stress, including deep breathing techniques, meditation, muscle relaxation, yoga, cognitive training, and potentially seeking consultation with a psychologist.37 An integrated exercise and nutrition plan can be incorporated into the program to provide psychological relief, motivating and encouraging patients to engage in prompt mental and physical preparation before their planned surgery.

Preoperative education is advocated in conjunction with psychological interventions. Such education, encompassing information pertaining to surgery and anesthesia, perioperative management, and pain control, has been demonstrated to mitigate anxiety and enhance patient satisfaction.38 The multimodal prehabilitation approaches4,11,13,33-37 are outlined in Table 2.

Prehabilitation for specific groups of patients

Strengthening the functional reserve prior to surgery constitutes the core principle of prehabilitation. It is

essential to note that while specific interventions primarily target patient cohorts vulnerable to surgical stress, certain individuals, particularly those identified as such, may require tailored prehabilitation interventions to optimize their surgical outcomes.

Frail surgical patients

Frailty denotes the age-related process encompassing both functional and cognitive decline, which subsequently elevates the risk of 30-day postoperative complications and 1-year mortality.39 Despite the absence of a standardized universal prehabilitation regimen for frailty,40 adopting a multimodal prehabilitation strategy could be beneficial. Such a program for frail patients may include41:

1. Moderate to intense aerobic exercise and resistance training targeting muscles essential for daily functioning, such as the upper and lower limbs, for 75-90 minutes, twice per week

   
   

   TABLE 2. The multimodal prehabilitation approaches.4,11,13,33-37

   
   

   1) Physical exercise intervention

Aerobic exercise: 30 min/day, 2-3 Resistance exercise: 8-15 Flexibility and balance: 2-3 times/ times/week, maintaining the target repetitions/set for 1-2 sets, week, holding each position for heart rate of 50-80% of age-adjusted 2 times/week, targeting the 20-30 sec, including:

maximal heart rate, such as: strengthening of muscles essential standing on one leg walking for daily activities including arms, lateral thigh lift

cycling shoulders, chest, abdomen, back, and single-leg squat

running legs. Examples of exercises include: stretching

hiking push-ups yoga

swimming weight lifting etc.

etc. abdominal curls

etc.

Enteral nutrition is prioritized, with a protein intake of A 60-min session with a psychological expert is

1.2-1.5 g/kg supplemented by an additional 20-30 g recommended to reduce anxiety and negative mood of protein following aerobic exercise. effects.

An intake of 140 g of carbohydrates is recommended Psychological support also enhances patient motivation 3 hours before exercise to support glycogen storage in and compliance with the prehabilitation program.

the muscles and liver. Examples of techniques for psychological support Arginine and omega-3 fatty acids are supplemented to include:

enhance immune function. mindfulness

meditation deep breathing

muscle relaxation positive thinking etc.

Abbreviations: min: Minute; sec: Second

1. Dietary adjustments tailored to body weight and composition, aiming for an intake of 25-30 kcal/kg and protein intake of 1.5 g/kg, initiated 4 weeks prior to surgery and supplementation with arginine and omega-3 fatty acids to enhance immune function

2. Psychological prehabilitation coupled with patient education

Overall, the implementation of multimodal prehabilitation interventions in frail patients is strongly recommended (1B-1C recommendation) to enhance postsurgical outcomes.40

Cancer patients

Multimodal prehabilitation remains a mainstream practice, with recent systematic reviews focusing on

exercise training programs for cancer patients. These programs typically include a warm-up period of 5-10 minutes, followed by a 30-minute session comprising aerobic and resistance exercises or aerobic training alone, concluding with a 5-10-minute cool-down period. Sessions are typically conducted 3-4 times per week over a span of 4 weeks. As a consequence of the limited number of studies and low sample size, the benefit of exercise prehabilitation in cancer patients is not apparent. However, there is a tendency towards the advantages of prehabilitation for reductions in the length of hospital stay and postoperative complications.42

Elderly patients

Among the elderly population aged over 65 years,

baseline health can be stratified into three groups: good health, pre-frail (experiencing normal aging), and frail (exhibiting pathological presentation). Regardless of initial health status, a decline in functional capacity is typically observed after surgery, with recovery to the baseline preoperative level often taking several months.43 With the implementation of moderate to intense aerobic and resistance exercise aiming for 80% of the maximum heart rate, 1.2-1.5 g/kg/day of protein intake with the supplementation of 20-30 g whey protein after aerobic exercise, and an anxiety relief program, an increase in muscle strength, muscle power, and VO2 max is observed.44

Prehabilitation and Enhanced Recovery After Surgery (ERAS)

ERAS has been recommended in the intraoperative care plan to promote early recovery and prevent adverse outcomes.45-52 However, there are a limited number of studies investigating the beneficial association between prehabilitation and the ERAS protocol. While ERAS has the potential to independently mitigate surgical stress and optimize surgical outcomes, some research has demonstrated an expedited return to baseline functional status, referred to as surgical resilience, among patients who undergo preoperative prehabilitation followed by ERAS intervention. Patients undergoing a multimodal prehabilitation plan demonstrated superior preservation of muscle mass and walking capacity, as determined by the 6MWT after surgery, compared to those who received only the ERAS protocol.53,54 Collectively, prehabilitation serves as a complement to ERAS by targeting the reduction of surgical stress through the enhancement of preoperative functional reserve. Nevertheless, the effectiveness of prehabilitation relies on both the baseline functional capacity and adherence to multimodal interventions.

The independent factors contributing to adverse postoperative outcomes include advanced age (≥ 75 years), smoking, hypertension, kidney disease requiring dialysis, body mass index (BMI) ≥ 30 kg/m², chronic steroid use, and American Society of Anesthesiologists (ASA) physical status classification ≥ 3.55 These risks for adverse postoperative outcomes are largely attributed to old age and frailty, characterized by a decline in the functional capacity and performance of organ systems, as well as cognitive function. Therefore, the implementation of prehabilitation for elderly and frail patients, as previously discussed in this context, is required.

While prehabilitation is not novel in the fields of surgery and anesthesia, its integration into ERAS protocols for ensuring optimal recovery and reducing postoperative complications is not widely practiced in routine clinical settings, particularly in Thailand. A concise overview is provided in this article regarding prehabilitation and its interaction with personalized protocols tailored to individual patients, aiming to enhance clinical outcomes and mitigate adverse postoperative events. The integration scheme4,53,54,56 of prehabilitation and ERAS targeting favorable postoperative outcomes is demonstrated in Fig 1.

Integrating prehabilitation into clinical practice through a multidisciplinary collaboration

Prehabilitation necessitates multifaceted collaboration among various healthcare professionals. Commencing with the mutual agreement between surgeons and patients regarding the forthcoming operation, the subsequent step involves preoperative screening for risk stratification and patient optimization, typically conducted in the preoperative clinic. The responsible team comprises clinicians from diverse specialties, nurses, and notably

Fig 1. Integration of prehabilitation and ERAS in surgical care to improve postoperative outcomes4,45,46,54

anesthesiologists, who conduct preoperative evaluations in the preanesthetic clinic. After preoperative evaluation, the baseline functional assessments are determined by the prehabilitation team, which includes physiotherapists, exercise trainers, nutritionists, pharmacists, psychologists, smoking and alcohol cessation counselors, and other pertinent healthcare personnel. Prehabilitation interventions are implemented. This thorough preoperative evaluation and the subsequent prehabilitation program serve as a preparatory platform for elective surgery patients before their scheduled procedures.4,57

Future directions in prehabilitation

Several studies have investigated the implementation of prehabilitation programs for patients undergoing various surgical procedures. These multimodal interventions have shown promising results in enhancing patients’ functional capacity and reducing postoperative complications.18,40,42 However, despite the documented benefits of multimodal prehabilitation in improving functional capacity, there remains limited effectiveness among vulnerable patients with low baseline functional reserve and poor adherence to interventions. Previous studies on prehabilitation have shown variations in study design, sample size, and outcome measurement. Furthermore, adherence to prehabilitation protocols varies widely across studies, ranging from 16% to 97%.58 Therefore, there is room for improvement in the form of prudent preoperative risk prediction, involving mutual decision-making among multidisciplinary care teams to tailor personalized prehabilitation interventions. Given the association of cognitive decline with aging, frailty, and malignancy, there is growing interest in integrating cognitive stimulation training into prehabilitation programs alongside exercise, nutrition, and psychological approaches, which are the cornerstones of the prehabilitation concept.59,60

CONCLUSION

Multimodal prehabilitation represents a preoperative strategy aimed at mitigating the stresses associated with subsequent surgery and anesthesia. Integrating prehabilitation with ERAS protocols can enhance functional capacity and fortify surgical resilience, thereby reducing complications during and after the operation. While exercise intervention plays a prominent role in the efficacy of prehabilitation, the significance of nutritional and psychological support is less apparent. A possible application to current perioperative practice is the integration of a preoperative prehabilitation program for indicated patients, emphasizing individualized care aimed at enhancing functional capacity in parallel with

the intraoperative ERAS protocol. However, a knowledge gap exists that future research needs to address to refine interventions and establish clear outcome measures, thereby fully exploring the potential of prehabilitation as a multidisciplinary approach to improving postoperative outcomes.

ACKNOWLEDGEMENTS

The authors wish to express their gratitude for the insightful suggestions provided by Assoc. Prof. Dr. Arunotai Siriussawakul and for the administrative support from Mr. Pichanon Choosaeng, Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University. Additionally, the authors extend their appreciation to Mr. Graeme Kay for his invaluable assistance with the English-language editing of this manuscript.

Author Contributions

PS was responsible for conceptualization, data curation, manuscript writing, and the review of the final manuscript. AJ contributed to data curation and the writing of the initial draft. NN managed data curation. All authors have read and approved the final manuscript.

DECLARATION

Funding

No funding was received for conducting this study.

Conflicts of interest

The authors declare that there are no conflicts of interest.

REFERENCES

1. World Health Organization. Ageing and health. WHO. 2022. [cited 2024 May 4]. Available from: https://www.who.int/ news-room/fact-sheets/detail/ageing-and-health

2. United Nations. World Social Report 2023: Leaving no one behind in an ageing world. Department of Economic and Social Affairs. 2023. [cited 2024 May 4]. Available from: https://www.un.org/development/desa/dspd/wp-content/ uploads/sites/22/2023/01/WSR_2023_Chapter_Key_Messages. pdf

3. Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A Review. JAMA Surg. 2017;152(3):292-8.

4. Carli F. Prehabilitation for the Anesthesiologist. Anesthesiology. 2020; 133(3):645-52.

5. Molenaar CJL, Papen-Botterhuis NE, Herrle F, Slooter GD. Prehabilitation, making patients fit for surgery - a new frontier in perioperative care. Innov Surg Sci. 2019; 4(4):132-8.

6. Arena R, Myers J, Williams MA, Gulati M, Kligfield P, Balady GJ, et al.American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Nursing. Assessment of functional capacity in clinical and

   research settings: a scientific statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing. Circulation. 2007;116(3): 329-43.

7. Snowden CP, Prentis JM, Anderson HL, Roberts DR, Randles D, Renton M, et al. Submaximal cardiopulmonary exercise testing predicts complications and hospital length of stay in patients undergoing major elective surgery. Ann Surg. 2010; 251(3):535-41.

8. Carli F, Awasthi R, Gillis C, Baldini G, Bessissow A, Liberman AS, et al. Integrating prehabilitation in the preoperative clinic: a paradigm shift in perioperative care. Anesth Analg. 2021;132: 1494-500.

9. Topp R, Ditmyer M, King K, Doherty K, Hornyak J 3rd. The effect of bed rest and potential of prehabilitation on patients in the intensive care unit. AACN Clin Issues. 2002;13(2):263- 76.

10. Carli F, Zavorsky GS. Optimizing functional exercise capacity in the elderly surgical population. Curr Opin Clin Nutr Metab Care. 2005;8(1):23-32.

11. Gonçalves CG, Groth AK. Prehabilitation: how to prepare our patients for elective major abdominal surgeries? Rev Col Bras Cir. 2019;46(5):e20192267.

12. Kothmann E, Batterham AM, Owen SJ, Turley AJ, Cheesman M, Parry A, et al. Effect of short-term exercise training on aerobic fitness in patients with abdominal aortic aneurysms: a pilot study. Br J Anaesth. 2009;103(4):505-10.

13. Le Roy B, Selvy M, Slim K. The concept of prehabilitation: What the surgeon needs to know? J Visc Surg. 2016;153(2): 109-12.

14. Ferguson M, Shulman M. Cardiopulmonary Exercise Testing and Other Tests of Functional Capacity. Curr Anesthesiol Rep. 2022;12(1):26-33.

15. Glaab T, Taube C. Practical guide to cardiopulmonary exercise testing in adults. Respir Res. 2022;23(1):9.

16. Myers J, Oliveira R, Dewey F, Arena R, Guazzi M, Chase P, et al. Validation of a cardiopulmonary exercise test score in heart failure. Circ Heart Fail. 2013;6(2):211-8.

17. Otto JM, Levett DZH, Grocott MPW. Cardiopulmonary Exercise Testing for Preoperative Evaluation: What Does the Future Hold? Curr Anesthesiol Rep. 2020;10:1-11.

18. Moran J, Wilson F, Guinan E, McCormick P, Hussey J, Moriarty

    J. Role of cardiopulmonary exercise testing as a risk-assessment method in patients undergoing intra-abdominal surgery: a systematic review. Br J Anaesth. 2016;116(2):177-91.

19. Hlatky MA, Boineau RE, Higginbotham MB, Lee KL, Mark DB, Califf RM, et al. A brief self-administered questionnaire to determine functional capacity (the Duke Activity Status Index). Am J Cardiol. 1989;64(10):651-4.

20. Wijeysundera DN, Beattie WS, Hillis GS, Abbott TEF, Shulman MA, Ackland GL, et al. Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study. Br J Anaesth. 2020;124(3):261-70.

21. Dias C, Torriani-Pasin C, Galvão ACJ, Costa PHV, Polese JC. Validation of the Duke Activity Status Index questionnaire by telephone in individuals after stroke. Int J Cardiol Cardiovasc Risk Prev. 2023;19:200208.

22. Sinclair RC, Batterham AM, Davies S, Cawthorn L, Danjoux GR. Validity of the 6 min walk test in prediction of the anaerobic

    threshold before major non-cardiac surgery. Br J Anaesth. 2012;108(1):30-5.

23. Shulman MA, Cuthbertson BH, Wijeysundera DN, Pearse RM, Thompson B, Torres E, et al. Using the 6-minute walk test to predict disability-free survival after major surgery. Br J Anaesth. 2019;122(1):111-9.

24. Giannitsi S, Bougiakli M, Bechlioulis A, Kotsia A, Michalis LK, Naka KK. 6-minute walking test: a useful tool in the management of heart failure patients. Ther Adv Cardiovasc Dis. 2019;13: 1753944719870084.

25. Struthers R, Erasmus P, Holmes K, Warman P, Collingwood A, Sneyd JR. Assessing fitness for surgery: a comparison of questionnaire, incremental shuttle walk, and cardiopulmonary exercise testing in general surgical patients. Br J Anaesth. 2008;101(6):774-80.

26. Singh SJ, Morgan MD, Hardman AE, Rowe C, Bardsley PA. Comparison of oxygen uptake during a conventional treadmill test and the shuttle walking test in chronic airflow limitation. Eur Respir J. 1994;7(11):2016-20.

27. Rodseth RN, Biccard BM, Le Manach Y, Sessler DI, Lurati Buse GA, Thabane L, et al. The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis. J Am Coll Cardiol. 2014;63(2):170-80.

28. Schmidt G, Frieling N, Schneck E, Habicher M, Koch C, Rubarth K, et al. Preoperative routine measurement of NT-proBNP predicts postoperative morbidity after non-cardiac surgery with intermediate or high surgical risk: an observational study. BMC Anesthesiol. 2024;24(1):113.

29. Devereaux PJ, Ofori S. Utility of pre-operative cardiac biomarkers to predict myocardial infarction and injury after non-cardiac surgery. Eur Heart J Acute Cardiovasc Care. 2023;12(11):740-2.

30. Meister R, Puelacher C, Glarner N, Gualandro DM, Andersson HA, Pargger M, et al. Prediction of perioperative myocardial infarction/injury in high-risk patients after noncardiac surgery. Eur Heart J Acute Cardiovasc Care. 2023;12(11):729-39.

31. Duceppe E, Borges FK, Conen D, Tiboni M, Chan MTV, Patel A, et al. Association of Preoperative Growth Differentiation Factor-15 Concentrations and Postoperative Cardiovascular Events after Major Noncardiac Surgery. Anesthesiology. 2023;138(5): 508-22.

32. West MA, Wischmeyer PE, Grocott MPW. Prehabilitation and Nutritional Support to Improve Perioperative Outcomes. Curr Anesthesiol Rep. 2017;7(4):340-9.

33. Weimann A, Braga M, Carli F, Higashiguchi T, Hübner M, Klek S, et al. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr. 2017;36(3):623-50.

34. Weimann A, Braga M, Harsanyi L, Laviano A, Ljungqvist O, Soeters P, et al. ESPEN Guidelines on Enteral Nutrition: Surgery including organ transplantation. Clin Nutr. 2006;25(2):224-44.

35. Campbell WW, Leidy HJ. Dietary protein and resistance training effects on muscle and body composition in older persons. J Am Coll Nutr. 2007;26(6):696S-703S.

36. Burke LM, Hawley JA, Ross ML, Moore DR, Phillips SM, Slater GR, et al. Pre-exercise aminoacidemia and muscle protein synthesis after resistance exercise. Med Sci Sports Exerc. 2012;44(10): 1968-77.

37. Tsimopoulou I, Pasquali S, Howard R, Desai A, Gourevitch D,

    Tolosa I, et al. Psychological prehabilitation before cancer surgery: a systematic review. Ann Surg Oncol. 2015;22(13): 4117-23.

38. Shuldham C. A review of the impact of pre-operative education on recovery from surgery. Int J Nurs Stud. 1999;36(2):171-7.

39. Van Kuiken ME, Zhao S, Covinsky K, Boscardin J, Finlayson E, Suskind AM. Frailty Is Associated with an Increased Risk of Complications and Need for Repeat Procedures after Sling Surgery in Older Adults. J Urol. 2022;207(6):1276-84.

40. Baimas-George M, Watson M, Elhage S, Parala-Metz A, Vrochides D, Davis BR. Prehabilitation in Frail Surgical Patients: A Systematic Review. World J Surg. 2020;44(11):3668-78.

41. Wong HMK, Qi D, Ma BHM, Hou PY, Kwong CKW, Lee A, et al. Multidisciplinary prehabilitation to improve frailty and functional capacity in high-risk elective surgical patients: a retrospective pilot study. Perioper Med (Lond). 2024;13(1):6.

42. Meneses-Echavez JF, Loaiza-Betancur AF, Díaz-López V, Echavarría-Rodríguez AM, Triana-Reina HR. Prehabilitation programs for individuals with cancer: a systematic review of randomized-controlled trials. Syst Rev. 2023;12(1):219.

43. Carlisle JB. Pre-operative co-morbidity and postoperative survival in the elderly: beyond one lunar orbit. Anaesthesia. 2014;69 Suppl 1:17-25.

44. Malot C, Durand-Bouteau A, Barizien N, Bizard A, Kennel T, Fischler M, et al. Prehabilitation Program in Elderly Patients: A Prospective Cohort Study of Patients Followed Up Postoperatively for Up to 6 Months. J Clin Med. 2021;10(19):4500.

45. Heng G, Lohsiriwat V, Tan K-Y. Suitability of Enhanced Recovery after Surgery (ERAS) Protocols for Elderly Colorectal Cancer Patients. Siriraj Med J. 2019;72(1):18-23.

46. Suenghataiphorn T, Songwisit S, Tornsatitkul S, Somnuke P. An Overview on Postoperative Cognitive Dysfunction; Pathophysiology, Risk Factors, Prevention and Treatment. Siriraj Med J. 2022; 74(10):705-13.

47. Tawantanakorn T, Phibalyart W, Parakonthun T, Nampoolsuksan C, Suwatthanarak T, Srisuworanan N, et al. Changes in Physical Components after Gastrectomy for Adenocarcinoma of Stomach and Esophagogastric Junction. Siriraj Med J. 2023;75(4):241-9.

48. Nampoolsuksan C, Parakonthun T, Tawantanakorn T, Mora A, Swangsri J, Akaraviputh T, et al. Short-term Postoperative Outcomes Before and After the Establishment of the Siriraj Upper Gastrointestinal Cancer Center: A Propensity Score Matched Analysis. Siriraj Med J. 2020;72(4):215-320.

49. Jiamton S, Jantanapornchai N, Nokdhes Y-N, Patthamalai P, Tantrapornpong P, Nanchaipruek Y, et al. Lidocaine Reducing Pain from Benzathine Penicillin Injection: A Controlled Trial. Siriraj Med J. 2022;74(10):699-704.

50. Lohsiriwat V, Jaturanon P. Effect of Intraoperative Hypothermia on Surgical Outcomes after Colorectal Surgery within an Enhanced Recovery after Surgery Pathway. Siriraj Med J. 2019;71(1):52-8.

51. Banyong C, Chanruangvanich W, Thosingha O, Lohsiriwat V. Factors Predicting Prolonged Postoperative Ileus in Patients Undergoing Major Gastrointestinal Surgery. Siriraj Med J. 2022;74(9):537-4.

52. Lohsiriwat V. Mosapride Reduces Prolonged Postoperative Ileus after Open Colorectal Surgery in the Setting of Enhanced Recovery after Surgery (ERAS): A Matched Case-Control Study. Siriraj Med J. 2019;71(3):181-8.

53. Gillis C, Fenton TR, Sajobi TT, Minnella EM, Awasthi R, Loiselle SÈ, et al. Trimodal prehabilitation for colorectal surgery attenuates post-surgical losses in lean body mass: A pooled analysis of randomized controlled trials. Clin Nutr. 2019;38(3): 1053-60.

54. Li C, Carli F, Lee L, Charlebois P, Stein B, Liberman AS, et al. Impact of a trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study. Surg Endosc. 2013;27(4):1072-82.

55. Hu WH, Eisenstein S, Parry L, Ramamoorthy S. Risk Factors Associated with Postoperative Outcomes in Diverticular Disease Undergoing Elective Colectomy-A Retrospective Cohort Study from the ACS-NSQIP Database. J Clin Med. 2023;12(23):7338.

56. Scheede-Bergdahl C, Minnella EM, Carli F. Multi-modal prehabilitation: addressing the why, when, what, how, who and where next? Anaesthesia. 2019;74 Suppl 1:20-6.

57. Durrand J, Singh SJ, Danjoux G. Prehabilitation. Clin Med (Lond). 2019;19(6):458-64.

58. Lobo DN, Pavel Skořepa, Gomez D, Greenhaff PL. Prehabilitation: high-quality evidence is still required. Br J Anaesth. 2023;130(1): 9-14.

59. He Y, Zou W, Han X, Chen C, Zhang A, Sun N. Cognitive prehabilitation for geriatric patients undergoing elective surgery: a PRISMA-P-compliant protocol for a systematic review. BMJ Open. 2022;12(7):e060369.

60. Daksla N, Nguyen V, Jin Z, Bergese SD. Brain Prehabilitation for Oncologic Surgery. Curr Oncol Rep. 2022;24(11):1513-20.