Surgical Prehabilitation in Older and Frail Individuals: A Scoping Review

Abstract

Background:

Older individuals who are scheduled for elective procedures often have co-morbidities at baseline and may be classified as frail. Both older age and frailty are associated with poor fitness and preoperative deconditioning, which can be predictors of postoperative complications. Prehabilitation aims to improve preoperative health in order to reduce complications and expedite postoperative recovery. To date, the effect of prehabilitation on improving outcomes in older and frail individuals is unclear, and the evidence in support of multi-modal treatments is evolving.

Methods:

In this scoping review, searches of PubMed and Cochrane Library between August 2012 and August 2022 were performed to identify studies investigating the efficacy of prehabilitation prior to surgical procedures.

Results:

A total of 36 articles were included in the review. Most of these examined the efficacy of unimodal (n=21) prehabilitation interventions, most commonly exercise therapy. Multimodal prehabilitation programs (n=15) included a variety of intervention components (e.g., exercise training, nutrition, psychological intervention or geriatric consultation). The most commonly studied populations were patients with gastrointestinal cancer (mostly colorectal cancer). Exercise therapy and multimodal interventions are likely to be of greatest impact on postoperative functional decline in patients awaiting total knee or hip arthroplasty, and cancer-related resection surgery (e.g., due to colorectal, gastric or lung cancer) in older and frail patients.

Conclusions:

Presurgical prehabilitation showed the potential to diminish postoperative outcomes in older and frail patients prior to surgery. However, adequately powered, randomized controlled, assessor blinded intervention trials demonstrating overall benefit of prehabilitation are needed.

Aims

This scoping review aims to summarize the current literature on the efficacy of prehabilitation in older and frail individuals who are undergoing surgical procedures in order to support clinical protocols and inform future research.

Introduction

Over the past decade, prehabilitation has become increasingly important with regards to improving outcomes, particularly in surgery. Preparing older or frail individuals for upcoming surgeries and other invasive procedures is crucial, as these individuals tend to be at risk for higher rates of morbidity and mortality. For example, Shinall et al. [1] studied more than 430,000 mostly male patients who underwent a noncardiac surgical procedure with a mean age of 61 years and found that the 30-day mortality rate among patients who were frail far exceeded the 1% mortality rates that is often used to define high-risk surgery. This study reported that the 30-day mortality rate for “frail” patients who underwent the lowest-stress surgical procedures (e.g., cystoscopy) was 1.6% (95% confidence interval [CI], 1.2%-2.0%) and for moderate-stress surgical procedures (e.g., laparoscopic cholecystectomy) it was 5.1% (95% CI, 4.8%-5.5%). Among patients who were deemed “very frail,” the 30-day mortality rates were higher after the lowest-stress surgical procedures (10.3%; 95% CI, 7.7%-13.5%) and after the moderate-stress surgical procedures (18.7%; 95% CI, 17.7%-19.8%). For patients who were scored as frail and very frail, mortality continued to increase at 90 and 180 days, reaching 43% (95%CI, 41.7%-44.3%) for very frail patients at 180 days after moderate-stress surgical procedures.

Frailty may be a better predictor of poor surgical outcomes than age alone [2], and while there are many descriptions of frailty, there is no uniform consensus on its definition or how best to measure it. In general, frailty is a multidimensional clinical syndrome that involves lower thresholds of reserve and function from dysregulation across physiologic and molecular pathways that are involved with and may further cause vulnerabilities to multiple organ systems [3,4]. Nearly a quarter century ago, Fried et al. [3] described the “phenotype of frailty” that bears the hallmark of people with diminished endurance and strength, a higher risk of falls, disability, hospitalization and mortality.

In addition to frailty, other factors may be associated with complications in patients undergoing surgery. For instance, a recent study from the Netherlands [5] examined outcomes in octogenarians following major surgical procedures and found that, depending on the diagnosis, they had increased median length of stay, 30-day major morbidity, and 30-day mortality. Additional risk factors for overall complications in elderly patients scheduled for surgery include smoking and alcohol consumption [7], malnutrition [7], excessive polypharmacy [8], mental health disorders (e.g., preoperative depression or anxiety) [9,10], hemoglobin < 11 g/dl [7,11], diabetes and glycemic control (e.g., increased HBA1c) [7]. These studies and many others highlight the significant risks associated with surgical and other interventions performed on older and frail individuals, and it has been suggested that prehabilitation may be an important antidote that supports improved outcomes [6].

Prehabilitation involves either a single intervention (unimodal) or multiple interventions (multimodal), and it aims to increase patients’ health status prior to elective or scheduled surgeries and procedures. Prehabilitation typically begins weeks ahead of the surgery or procedure in preparation for the upcoming stressor. Increasingly, there is interest as to whether conventional care (i.e., the usual preoperative instructions and education and postoperative recovery recommendations) should be replaced with prehabilitation protocols (beginning weeks prior), early recovery programs (generally the 48-72 hour perioperative period), or both [12].

Prehabilitation has been understudied in older and frail individuals, and the aim of this review is to summarize the current literature in order to foster an understanding of the evidence-base that will support clinical protocols and inform future research.

Methods

The articles used in this scoping review were obtained in August 2022 using a search of PubMed and Cochrane Library databases. Articles published between August 1, 2012 and 1 August, 2022 were retrieved using search terms presented in eTable 1.

Identified articles were imported into the Covidence systematic review software (Melbourne, Australia). After removing duplicates, each article was screened independently by two study team members (MS, NBK, JSJ, LF). First, titles and abstracts were reviewed, followed by full texts for inclusion and exclusion criteria. For each article screen, disagreements were resolved by consensus (MS, NBK), and final article selections were based on a priori established inclusion and exclusion criteria (MS, NBK). Data on the study population, domains of prehabilitation, efficacy outcomes, and other study details were extracted by study team members (MS, NBK, JSJ, LF) into a preformatted Excel spreadsheet. Information from all included articles were then recorded and synthesized for the review.

Our inclusion criteria included studies (e.g., randomized controlled trials [RCTs], non-RCTs, non-controlled intervention trials, feasibility trials, case-control or prospective cohort studies) with adults that a) examined the efficacy of a unimodal or multimodal prehabilitation; b) examined an intervention with a duration of at least one week that was performed at least one week prior to surgery; and c) were available in English as full texts. Case reports, book chapters, letters to editor, systematic, scoping, and narrative reviews, study protocols, non-research-focused reports (e.g., perspective articles), and intervention trials of complementary medicine (e.g., acupuncture, spiritual intervention) were excluded.

Finally, articles were categorized according to subtopics including (1) characteristics of study population undergoing an intervention (unimodal or multimodal) prior to the scheduled procedure; (2) characteristics of unimodal or multimodal interventions prior to surgery (e.g., domains, duration, inpatient or outpatient setting); and (3) characteristics of efficacy outcomes, grouped into the following categories: physical performance and frailty (e.g., cardiopulmonary fitness, muscle strength), cognitive and psychological performance (e.g., neuropsychiatric assessment, quality of life [QoL]), health behavior outcomes (e.g., nutrition, alcohol and nicotine cessation), and perioperative outcomes (e.g., complications, length of hospital stay [LOS], in-hospital mortality).

Results

Search

The PubMed and Cochrane searches yielded 1,562 articles. After removing 95 duplicates, 1,467 were screened based on title and abstract review. After removing 1,389 based on title and abstract and upon full-text review of the remaining 78 articles, a total of 36 articles (n=21 for unimodal presurgical intervention and 15 articles for multimodal prehabilitation, Figure 1 and Table 1) were included. Articles were excluded most commonly due to intervention or participant characteristics (n=22) (e.g., ,duration less than one week, no surgical procedure); being an abstract (n=12), case report or study protocol (n=4), or systematic or narrative review (n=2); or being unavailable in English (n=2). The characteristics of the included studies are included in Table 1.

Figure 1.

Flow diagram revealing search results and reasons for exclusion

Table 1.

Study characteristics of articles included in this review

Author (Year)	N	Age (Mean/Median)	% Female	Mode	# of study arms and study design	Population (Surgery type)	Major Findings
Achilli et al (2020) [13]	175	78.3 (mean)	44.6	Unimodal - Nutrition Nutrition supplementation with arginine, omega-3 fatty acids, and nucleotides for 10-14 days prior to surgery	2 study arms, case-control study (control group = usual care)	Cancer - colorectal (colectomy, rectal resection with ileostomy/colostomy, rectal resection without ileostomy/colostomy, miles procedure)	■ Participants receiving immunonutrition had no significant difference in postoperative LOS (p=0.38) or complication rates (p=0.11) ■ Immunonutrition did not result in significantly shorter GI recovery time (p=0.04), lower rate of site infection complications (p=0.04), or less use of antibiotics (p=0.01)
An et al (2021) [28]	53	70.53 (mean)	100	Unimodal - Exercise Preoperative exercise training including mobility, strength, flexibility and balance, preoperative education on home exercise, or usual care for 3 weeks	3 study arms, single-blind RCT (two experimental, one control group = usual care)	Orthopedic - osteoarthritis (total knee arthroscopy)	■ Exercise telerehabilitation resulted in significantly improved time-by-group interaction for 60◦/s extension peak torque (p= 0.047), 180◦/s extension peak torque (p= 0.009), ROM (p= 0.002), TUG time (p< 0.001), WOMAC pain (p< 0.001), WOMAC functional outcome (p< 0.001), and WOMAC total score (p< 0.001)
Anan et al (2020) [38]	70	72.5 (median)	0	Unimodal - Exercise Preoperative pelvic floor exercise training for 28 days	2 study arms, RCT (control group received the prehabilitation intervention post-surgery)	Genitourinary - benign prostate hyperplasia (holmium laser enucleation of the prostate)	■ Pelvic floor therapy led to significantly decreased postoperative urinary incontinence rate at 3 months (p= 0.01) ■ Participants with pelvic floor therapy had no significant difference at 3 days (p= 0.34), 1 month (p= 0.34), and (p= 1.00) postoperatively
Baimas-Georg et al (2021) [23]	10	64 (mean)	40	Multimodal - Nutrition, Exercise, Pain Management Individualized multimodal intervention including pain management, aerobic exercise, diet, and supplements	1 study arm, prospective feasibility study	Cancer - pancreatic adenocarcinoma (pancreaticoduodenectomy, pancreatectomy with splenectomy, Roux-en-Y hepaticojejunostomy with gastrojejunostomy)	■ Comprehensive therapy significantly improved frailty (p< 0.0001), but there no differences in functional status, physical performance, psychosocial assessments, or nutrition
Bhatia et al (2019) [40]	151	64 (mean)	40	Unimodal - Exercise High intensity interval training performed using cycle ergometer 2-3 times a week	2 study arms, RCT (control group = usual care)	Cancer - lung (resection)	■ HIIT caused a significant decrease in HR at rest from first to third session (p<0.001) and significant increase in VO2peak (p=0.004), Wpeak (p<0.01), and 6MWT waking distance (p<0.001)
Bojensen et al (2022) [14]	8	80 (mean)	40	Multimodal - Nutrition, Exercise, Medicine Nutrition: addition of 0.4kg of protein twice daily following exercise and before bed Exercise: high intensity interval training and resistance training Medical: smoking/alcohol cessation, optimization of bloodwork	1 study arm, prospective feasibility study	Cancer - colorectal (laparoscopic, laparotomy)	■ Adherence to the training sessions and nutritional support were 87% and 57%, respectfully
Briguglio et al (2020) [30]	73	67.3 (mean)	59	Unimodal - Nutrition Intervention: dietary supplement with sucrosomial ferric pyrophosphate plus L-ascorbic acid	2 study arms, open-label RCT with no placebo (control group = usual care)	Orthopedic - general (total hip or knee arthroplasty)	■ Supplementation with sucrosomial ferric pyrophosphate plus L-ascorbic acid resulted in a significant difference in circulating hemoglobin from baseline with patients without intervention loosing 2.8±5.1% and the intervention group gaining 0.7±4.6% (p=0.019)
Brown et al (2012) [29]	18	NR	NR	Unimodal - Exercise Exercise program including resistance training, stretching, and step exercises 3 times a week for 8 weeks	2 study arms, RCT (control group = usual care)	Orthopedic - osteoarthritis (total knee arthroplasty)	■ Physical therapy resulted in significant improvement only on the physical functioning domain only of the SF-36 compared to those that did not have therapy (p=0.04)
Bruns et al (2019) [15]	14	79 (median)	64	Multimodal - Nutrition, Exercise Fit4SturgeryTV At-home Prehabilitation is a home-based, adaptable digital program. Program utilizes social and digital rewards. Exercise: strength training and mobility. Nutrition: meal delivery of meals with 20-30 grams of protein.	1 study arm, prospective feasibility study	Cancer - colorectal (laparoscopic, open hemicolectomy, low anterior resection, trans anal endoscopic microsurgery)	■ Patients performed an average of exercises 6 days/week (86%) and complete the dietary component of the process 5 d/week (71%) ■ With at-home nutritional and exercise therapy, from baseline to follow up, median hand grip strength declined, median clinical frailty score remained the same, and median fried score, 4-m GS, short physical performance battery, and overall QoL (EORTC) increased
Carli et al (2020) [16]	110	78 (mean)	53	Multimodal - Nutrition, Exercise, Psychology Personalized, home-based, and supervised intervention. Exercise: aerobic, resistance, and flexibility training. Nutrition: targeted protein intake of 1.5 g/kg and supplementation if needed. Psychological: development of coping strategies, and discussion of anxiety/depression.	2 study arms, RCT (control group = received intervention following surgery)	Cancer - colorectal (ileocecal resection, hemicolectomy, subtotal colectomy, anterior/sigmoid resection, transverse colectomy, low anterior resection, abdominoperineal resection, other)	■ Multimodal therapy before surgery resulted in no significant difference in 30-day Comprehensive Complications Index (p=0.45), severe complications (p=0.90), primary and total LOS (p=0.80 and p=0.32, respectfully), ED visits (p=0.21), readmissions (p=0.18), preoperative walking capacity (p=0.37), postoperative walking capacity (p=0.34), self-reported generic health status (SF-36) (p=0.90), anxiety/depression (HADS) (p=0.46/p=0.58), or energy expenditure (community healthy activities model) (p=0.65) compared to postoperative therapy only
Gilbert et al (2021) [18]	147	79.6 (median)	73	Unimodal - Nutrition Multi-professional assessment was used to categorize patients as sever under-nutrition, moderate undernutrition, or no under-nutrition. Length of immunomodulating nutritional supplement administration was based on categorization.	2 study arms, open-label randomized trial with a stepped-wedge design (control group = usual care)	Cancer - colorectal (NR)	■ Nutritional therapy in undernourished patients resulted in no significant difference in improvement (p=0.4367) or postoperative complications (p=0.7576) ■ During the control phase, compared with addition of nutritional supplementation, patients had significantly more frequent digestive complications (p=0.305)
Gillis et al (2021) [17]	55	77 (mean)	47	Multimodal - Nutrition, Exercise, Psychology Nutrition: focused on balanced eating, barriers to adequate food intake, and meeting 1.5g/kg protein requirement Exercise: weekly supervised training with a kinesiologist including aerobic exercise, resistance training, and stretching Psychology: personalized coping strategies and deep breathing exercises	2 arms, secondary analysis of RCT (control group received intervention after surgery)	Cancer - colorectal (NR)	■ 61% of the <400 m 6MWD group experienced at least one complication within 30 days of surgery compared to 21% in the ≥400 m group (P=0.009) ■ Patients unable to attain a minimum 400 m 6MWD compared to patients that could attain this distance preoperatively after therapy had significantly longer LOS (p=0.020) and were significantly more likely to suffer a postoperative complication (p=0.041) ■ The ≥400 group had significantly lower depression scores (p=0.047) and an improvement from baseline in pain (p=0.029) and total physical score (p=0.047)
Goldsmith et al (2020) [41]	216	71.7 (mean)	49.5	Multimodal - Exercise, Education Exercise: Supervised twice weekly sessions at dedicated prehabilitation centers as well as home exercises three times daily. Intervention included respiratory muscle training, breathing exercises, Education: health and smoking cessation, and pharmacologic agents.	1 study arm, prospective cohort study	Cancer - lung (lobectomy, segmental resection, pneumonectomy, wedge resection, endobronchial excision of tumor/open and shut thoracotomy - minimally invasive approach, standard thoracotomy)	■ Pulmonary therapy led to a significant improvement in dyspnea scores (p= 0.00002), frailty index (p= 0.0006), and 6MWT (p= 0.04)
Grundmann et al (2018) [36]	82	C:75, I:72 (median)	21	Unimodal - Nutrition Intervention group received calorie-restricted diet of 60% of daily energy expenditure. The diet was maintained for 1 week prior to surgery.	2 study arms, randomized open-label study (control group = ad libitum diet)	Cardiac - coronary artery disease and heart valve disease (coronary artery bypass grafting and valve surgery)	■ Calorie restriction did not cause a significant between-group difference in median serum creatinine increment after 24 hours (p=0.39) ■ Patients that restricted calories had significantly smaller rise in median creatinine at 48 hours compared to control (p=0.03) and continued until discharge (p=0.0006), and the benefit was most pronounced in male patients and patients with BMI>25 ■ There was no significant difference in safety related events between groups
Halliday et al (2021) [27]	111	Unmatched –I:68, C:67 (unmatched); Matched- I:69, C:68 (median)	NR	Multimodal - Nutrition, Exercise, Psychology PREPARE program (Physical activity, Respiratory exercises, Eat well, Psychological well-being, Ask about medications, Remove bad habits, Enhanced recovery). Program is individualized and delivered at home.	2 study arms, case-control study (control group = usual care)	Cancer - esophageal (resection)	■ Mulitmodal therapy led to significantly lower incidence of postoperative pneumonia (p= 0.001) and a shorter LOS (p=0.018) ■ There was no significant difference in the incidence of overall complications or severe complications
Hermann et al (2016) [33]	80	70.4 (mean)	65	Unimodal - Exercise Patients attended a supervised preoperative progressive explosive-type resistance training twice a week for 10 weeks	2 study arms, RCT (control group = usual care)	Orthopedic - osteoarthritis (total hip arthroplasty)	■ Explosive-type resistance training significantly improved HOOS ADL (p<0.001), resulted in significantly better scores for all HOOS sub scales (p<0.03), and higher leg extension muscle power (p<0.0001)
Holsgaard-Larsen et al (2020) [34]	80	70.4 (mean)	70	Unimodal - Exercise (same as Hermann et al. 2016)	2 study arms, secondary analysis of RCT (control group = usual care)	Orthopedic - osteoarthritis (total hip arthroplasty)	■ Explosive-type resistance training resulted in significant differences at 3 months for HOOS-Sport/Rec (p=0.023) and higher knee strength of the affected side (p<0.001) ■ Explosive-type resistance training did not have a significant impact at 12 months for HOOS ADL (p=0.44) or remaining subscales
Janssen et al (2019) [20]	627	C:76, I:77 (median)	C:37.5; I:35.2	Multimodal - Nutrition, Exercise, Medicine Patients were assessed by a physical therapist, nurse practitioner, and dietitian. Exercise: home-based, individualized exercise programs focused on aerobic training, resistance training, and respiratory muscle training. Nutrition: minimum daily protein intake of 1.2g/kg bodyweight. Anemic patients received intravenous iron injection during admission. Medicine: Some patients completed visits with geriatrician to assess need for delirium prevention interventions.	2 study arms, case-control study (control group = usual care)	Cancer/Vascular - colorectal, abdominal aortic aneurysm (laparoscopic or open tumor resection, open or fenestrated endovascular aorta repair)	■ Multimodal therapy led to a significant reduction of incidence of delirium (p=0.043), increased prevalence of more serious complication (p=0.036), shorter LOS (p=0.003), and higher rate of mortality (p=0.034) ■ There was a non-significant difference in overall complications between groups (p=0.32)
Kaye et al (2020) [39]	43	71 (mean)	24	Unimodal - Exercise Exercise intervention was based on relative physical exertion scale and was supervised by an exercise physiologist or trainer. Participants completed three, 90-minute exercise sessions per week for 4 weeks	1 study arm, uncontrolled experimental study	Cancer/Genitourinary - bladder (cystectomy and urinary diversion)	■ Exercise intervention resulted in improvements in functional outcomes across physical domains with significant increase in total distance walked (p<0.001) and submaximal exercise (p<0.001) ■ Unimodal exercise therapy resulted in significant improvement in patient-reported quality-of-life (SF-36) with improvements in mental health 90-days post-operative (p=0.014) and higher than baseline at 30 days (p=0.11) and 90 days post-operative (p=0.004)
Kim et al (2021) [31]	43	67.1 (mean)	44	Unimodal - Exercise Intervention group completed three 60-minute aquatic exercise sessions three times a week for 4-8 weeks	2 study arms, RCT (control group = usual care)	Orthopedic - osteoarthritis (total knee arthroplasty)	■ Aquatic therapy was associated with more favorable outcomes in WOMAC scores (p<0.01), chair- stand (p=0.019), MAT-sf as well as improved depression (p=0.043) and cognition (p=0.008) ■ Aquatic therapy did not lead to a statistically significant difference in combined outcome of any complication, ER visit, or disposition to nursing home/rehab facility
Koh et al (2022) [21]	81	C:77, I:78.5 (median)	C:48; I:43	Multimodal - Nutrition, Exercise, Medicine Programme for Enhanced Elderly Recovery at Sengkang General Hospital (PEERS) Nutrition: 3 weeks of oral nutrition supplementation Exercise: 3 weeks of resistance exercise training. Medicine: Consultation by geriatrician to optimize medications and symptoms, and a cardiovascular consultation to optimize cardiac risk factors.	2 study arms, nonrandomized sequential comparative prospective study (control group = usual care)	Cancer - colorectal (colectomy)	■ Multimodal therapy resulted in significantly shorter LOS (p= 0.01), improvement in WOMAC scores (p< 0.01), chair-stand (p= 0.019), MAT-sf as well as improved depression (p= 0.043) and cognition (p= 0.008) with intervention, but no significant difference in 30-day morbidity rates (p=0.26) ■ Multimodal therapy had no significant impact on anthropometric and functional characteristics
Lai et al (2016) [42]	60	C:71.6, I:72.5 (mean)	C:40; I:46.7	Unimodal - Exercise Exercise intervention consisting of preoperative pulmonary rehabilitation, inspiratory muscle training, and aerobic endurance training for one week	2 study arms, RCT (control group = no pulmonary rehabilitation)	Cancer - non-small cell lung (lobectomy)	■ Exercise therapy led to significantly less postoperative pulmonary complications (p=0.037), reduced postoperative LOS (p=0.010) and total in-hospital stay (p=0.012), increased 6-MWD (p=0.029), and increased PEF (p<0.001) ■ Exercise intervention resulted in no significant difference in quality of life (p=0.785), physical function (p=0.691), emotional function (p=0.206), or dyspnea score (p=0.808)
Lindbäck et al (2018) [35]	197	C:61, I:58 (mean)	C:52; I:54	Unimodal - Exercise Patients received physiotherapy twice a week for nine weeks prior to surgery. The program included physiotherapy according to treatment-based classification, tailor-made general supervised exercise programming, and behavioral approaches to reduce fear avoidance and increase activity level.	2 study arms, RCT (control group = standard pre-surgery information)	Orthopedic - degenerative lumbar spine disorder (NR)	■ Patients with physical therapy had improvements that were larger than study-specific minimal clinical important change in VAS back and leg pain, EQ-5D, and FABQ-PA
Malot et al (2021) [43]	139	<65yo:56, >65yo:75 (mean)	<65yo:52; >65yo:44	Multimodal - Nutrition, Exercise, Psychology Exercise: 4 week intervention included home-based, personalized exercise programming including both aerobic and resistance exercises. Nutrition: counseling with protein supplements Psychology: coping strategies, and strategies to manage anxiety.	2 study arms, case-control study (control group = usual care)	General Surgical - general elderly (major abdominal and thoracic surgery)	■ There was no significant difference between age groups for postoperative complications or functional capabilities; both groups had significant increase in the 6 MWT from the initial evaluation to the last (p=0.114)
McIsaac et al (2022) [44]	182	C:74, I:74 (mean)	C:52.3; I:60.6	Unimodal - Exercise Home-based intervention program including one-hour exercise sessions at least 3 times a week. Sessions consisted of strength training, aerobic exercise, and flexibility training.	2 study arms, RCT (control group received global physical activity recommendations, Canada’s food guide, and a pedometer)	Cancer - colorectal, thoracic, hepatobiliary, urologic (resection)	■ Unimodal exercise intervention resulted in no significant difference in 6MWT at follow-up (p=0.486), quality of life (p=0.547, disability score (p=0.429), LOS (p=0.739), or 30-day readmission (p=0.674)
Okazaki et al (2013) [24]	48	C:78, I:79 (median)	C:43; I:48,	Unimodal - Nutrition Intervention group received 7 days of preoperative, and 10 days of postoperative symbiotic therapy consisting of Biolactics powder (Lactobacillus casei strain Shirota and BBG-01, a living Bifidobacterium breve strain Yakult, as well as galacto-oligosaccharides.)	2 study arms, RCT (control group = no symbiotic therapy)	Cancer - hepatobiliary pancreatic (gastroenterological)	■ Symbiotic therapy did not lead to significant difference in postoperative infectious complications (p= 0.06)
Rampam et al (2022) [45]	80	69 (mean)	53	Unimodal - Exercise Home-based intervention for 3-8 weeks in which patients received a pedometer that allowed trainer to monitor activity level and prescribe daily step counts. Athletic trainers increased step count goal by 10-20% each week during weekly check-in calls.	2 study arms, RCT (control group = general walking recommendations)	General Surgical (colorectal, thoracic, urological, transplant, oncological, vascular)	■ Walking therapy resulted in no significant difference in postoperative 6MWD (p=0.54), postoperative steps (p=0.76), or postoperative stamina (p=0.70)
Sorensen et al (2014) [19]	129	C:71, I:69 (mean)	C:51; I:41	Unimodal - Nutrition Patients received outpatient nutrition supplementation including marine omega-3 fatty acids (n-3 FA) 200 mL twice per day (morning and afternoon) for 7 days before surgery.	2 study arms, sub-study of a randomized, double-blind, prospective, placebo-controlled trial. (control group = standard outpatient nutrition supplementation without marine omega-3 fatty acids)	Cancer - colorectal (open, laparoscopic resection)	■ Supplementation with omega-3 fatty acids significantly increased the production of leukotriene B5 (p<0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p<0.01) as well as significantly decrease the production of leukotriene B4 (p<0.01) from stimulated neutrophils on day of surgery ■ For patients with this nutritional supplementation, there was no statistically significant difference in clinical outcomes (total number of complications, infectious complications, non-infectious complications, intensive care unit stay, mortality, readmissions and hospital stay) ■ There was no statistically significant association between proinflammatory LTB4 production and overall complications (p=0.524)
Tweed et al (2021) [22]	9	73 (median)	44	Multimodal - Nutrition, Exercise Exercise: 60-75 minute sessions 3 times a week for 4 weeks. Each session included strength training and aerobic exercise. Nutrition: provision of 3 protein-rich meals, and three snacks a day. Calorie content was calculated by a dietician and patients were instructed to maintain a food diary and abstain from eating other foods.	1 study arm, prospective feasibility study	Cancer - colorectal (resection)	■ Nutritional and exercise intervention resulted in a significant improvement in handgrip strength (p=0.02) and exercise capacity (p=0.02) ■ For both interventions, there was a compliance rate of >80% achieved by 66.7% of patients suggesting feasibility
van Leeuwen et al (2014) [32]	18	C:69.5, I:71.8 (mean)	C:50; I:30	Unimodal - Exercise Standard treatment included information on exercise, training of walking with aids, maintenance of mobility, and aerobic training, but did not include resistance training. The intensive strength training intervention group received standard treatment as well as a progressive strength training program focused on the lower limbs.	2 study arms, RCT (control group = usual care)	Orthopedic - osteoarthritis (total knee arthroplasty)	■ Strength training led to no significant differences in strength measures compared to standard training and no changes in time for total group ■ For both groups combined, chair stand (p=0.003) and 6MWT (p=0.013) significantly improved before surgery and changes over time were similar between groups
Vlisides et al (2019) [46]	52	C:68, I:66 (mean)	C:48; I:57	Unimodal - Cognitive Home-based intervention consisting of an adaptive, computer-based cognitive training battery that specifically targets executive function, attention, working memory, and visuospatial processing Patients completed adaptive training for seven days, with sessions lasting approximately 20 minutes per day.	2 study arms, RCT (control group = no training before surgery)	General Surgical (gastrointestinal, urologic, spine, hepatobiliary)	■ Home based cognitive therapy resulted in no significant difference in incidence of postoperative delirium (p=0.507)
Wada et al (2022) [25]	58	C:70.7, I:74.9 (mean)	C:30; I:33	Multimodal - Nutrition, Exercise Nutrition: advised to take in 25-30 kcal/kg and 0.8-1.2 g/kg of ideal body weight. Exercise: walking was recommended for 1 hour a day and patients were asked to perform leg exercises.	2 study arms, non-RCT (control group = usual care)	Cancer - gastric (gastrectomy)	■ Exercise and nutritional therapy led to significantly shorter LOS (p=0.03) and significantly improved the neutrophil–lymphocyte ratio (NLR) (p=0.03) ■ There was no significant difference between groups for operative time (p=0.14), estimated mean blood loss (p = 0.27), and postoperative complications (p = 0.08)
Waite et al (2017) [37]	22	NR	NR	Unimodal - Exercise Home-based intervention consisting of individualized exercise prescription. Exercises included strength-training with progressive levels and balance exercises.	1 study arm, exploratory clinical pilot study	Cardiac (coronary artery bypass graft and vale repair/replacement)	■ Home exercise therapy led to a significant difference in clinical frailty score (p=0.0003), 6MWT distance (p=0.0005), 6MWT speed (p=0.001), and short physical performance battery (p=0.0002); Change in 6MWT distance had a significant positive associated with LOS
Wooten et al (2021) [47]	24	64.9 (mean)	58	Multimodal - Nutrition, Exercise Exercise: home-based intervention with 4 in-person visits. Resistance training utilized resistance bands, hand-grip strengthening balls, exercise videos, and exercise logs. Exercises were performed 5-6 days a week for a 4 week period. Nutrition: pre-packaged nutrition supplements and nutrition logs.	1 study arm, prospective clinical pilot study	Cancer - abdominal (NR)	■ Nutrition and blood flow restriction exercise training resulted in a significant improvement in 6MWT, timed up and go, short physical performance battery, 5-chair stand test, and physical component score of quality of life following 4 weeks of intervention (all p<0.05)
Wooten et al (2022) [48]	92	C:58.8, I:64.9 (mean)	C:34; I:62	Multimodal - Nutrition, Exercise (same as Wooten et. al. 2021)	2 study arms, prospective, exploratory clinical pilot with matched control (control group = usual care)	Cancer - abdominal (NR)	■ Multimodal nutrition and exercise intervention had a significant association with shorter LOS (p=0.02) and decreased incidence of complication (p=0.03) ■ There was no significant association between this intervention and incidence of serious complications (p=0.17) or rate of readmission (p=0.59)
Yamamoto et al (2017) [26]	22	75 (mean)	55	Multimodal - Nutrition, Exercise Exercise: program included handgrip training, walking (>7500 steps/day), and resistance training. Nutritional: consisted of total calorie intake of > 28kcal/kg and 1.2g/kg of ideal body weight, as well as 2.4 g daily oral supplementation with leucine, metabolite b-hydroxy-b-methyl butyrate in nutritional counseling.	1 study arm, prospective exploratory clinical pilot	Cancer - gastric (open, laparoscopic gastrectomy)	■ Physical and nutrition therapy led to a significant increase in handgrip strength (p=0.022), total calorie intake (p=0.049), and protein intake (p=0.0019)

Note. NR = Not reported, C = Control group, I = Intervention group, RCT = Randomized controlled trial

Characteristics of study population

Among the trials included in this review, presurgical unimodal or multimodal interventions were examined in patients with: (1) colorectal cancer (n=10) [13–22], pancreatic or hepatobiliary pancreatic cancer (n=2) [23,24], gastric cancer (n=2) [25,26], and esophageal cancer (n=1) [27] undergoing a laparoscopic or open surgery, (2) knee osteoarthritis awaiting a total knee arthroplasty (TKA) (n=5) [28–32] or hip osteoarthritis scheduled for total hip arthroplasty (THA) (n=3) [30,33,34], (3) degenerative lumbar spine disorder (e.g., disc herniation, spinal stenosis, spondylolisthesis) scheduled for surgery (n=1) [35], (4) coronary or valve heart disease (n=2) [36,37] scheduled for coronary bypass graft surgery (CABG), valve replacement via sternotomy or transcatheter aortic valve replacement (TAVR), (5) prostate cancer (n=1) [38] undergoing Holmium laser enucleation (HoLEP) or bladder cancer (n=1) [39] undergoing cystectomy, (6) lung cancer (n=3) [40–42] undergoing resection surgery, and (7) diverse mostly cancer-related major surgeries (e.g., abdominal or intra-thoracic) (n=6) [43–48].

Details of included studies are presented in Table 1. Representative data from cited sources were used to generate a supporting figure for the review. Figure 2 summarizes the literature related to risk factors for poor surgical outcomes, types of prehabilitation interventions, surgical procedures for which prehabilitation has been studied, and efficacy outcomes of prehabilitation.

Figure 2.

Prehabilitation in older and frail patients

Characteristics of unimodal presurgical interventions

Of included articles, the majority examined the efficacy of unimodal (one intervention, n=21) compared to multimodal (more than one intervention, n=15) prehabilitation. The unimodal interventions included exercise (n=14) [17,28,29,31–33,35,37–40,42,44,45], nutrition (n=6) [13,18,19,24,30], and cognitive (n=1) [46] therapies.

Exercise Therapy

The unimodal exercise therapy prehabilitation studies focused on this intervention in patients undergoing a variety of surgical procedures including joint replacements (n=5) [28,29,31–33], spinal surgery (n=1) [35], cancer resection (n=4) [39,40,42,44], cardiac surgery (n=1) [37], prostate enucleation (n=1) [38], and major general surgeries (n=1) [45].

For patients undergoing musculoskeletal surgical procedures, exercise intervention specifics varied, though most were inclusive of at least strength and flexibility training. For patients awaiting TKA, interventions included comparing the impact of 3 weeks of sessions (mobility, flexibility, strength, balance, resistance training) with real-time feedback from a therapist versus independent practice [28], 6 weeks of therapy (activities of daily life, walking with aids, mobility, and aerobics) with and without strength training [32], 8 weeks of 45 minutes/week exercise sessions (resistance, flexibility, and step training) [29], and 4-8 weeks of 60 minute aqua therapy sessions (range of motion, flexibility, strength, and endurance exercises) 3x/week [31]. Sample size ranged from 18 to 53 individuals and 50% of these were home-based while the other half were based in outpatient therapy centers. Exercise therapy in these assorted programs was shown to improve functional outcomes [28,29,31], strength, range of motion, pain [28], as well as depression and cognition [31] after surgery, compared to standard care without prehabilitation. Though intensive strength training was feasible for most of the participants (73% participants were able to complete program without adaptations, remaining 27% completed program with minor adaptations), it may not be more effective than standard physical therapy for patients undergoing TKA for improving maximal knee extensor strength, voluntary activation, and functional test performance [32]. However, these findings may be limited by the small sample size and postoperative attrition, preventing detection of difference between groups. Whereas some studies assessed exercise programs inclusive of training beyond dedicated strength training including flexibility, balance, and ADLs, Hermann et al. [33] studied a specific type of strength training. This study [33] found that in patients awaiting THA (n=80), 10 weeks of an outpatient-based supervised progressive explosive-type resistance training program (exercises with maximal intentional acceleration of the load through the concentric phase) 2x/week resulted in significant improvement on the Hip disability and Osteoarthritis Outcome Score prior to undergoing THA compared to controls.

In addition to joint replacements, exercise prehabilitation has been shown to be beneficial for patients planning to have spinal surgery for degenerative lumbar spine disease [35]. Lindbäck et al. [35] found that 9 weeks of individualized, supervised outpatient physical therapy led to clinically meaningful improvements in back and leg pain, QoL, and fear avoidance. These studies assessing impact of exercise therapy on musculoskeletal conditions support its use in improving functional outcomes both prior to and following surgical procedures.

Exercise therapy preceding surgical cancer resection has also been studied for patients with non-small cell lung [40,42], bladder [39], and intra-abdominal/thoracic cancer [44]. Sample sizes ranged from 43 to 182 individuals. Three were performed in an outpatient setting [39,40,42] , while one [44] was home-based. In patients with non-small cell lung cancer, high intensity interval training (3x/week for 2-3 weeks) led to significantly improved functional capacity, as measured by peak oxygen consumption (VO2 peak), max power, peak aerobic power, and 6 minute walk test (6MWT) prior to surgery [40], and endurance and inspiratory muscle training (2-3x/day for one week) led to increased 6MWT distance and peak expiratory flow (a measure of ventilation) preoperatively as well as significantly decreased postoperative pulmonary complications and (length of stay) LOS [42]. Similarly, a four-week exercise intervention consisting of twelve, 90-minute sessions involving aerobic, resistance, flexibility, and strength training for patients with bladder cancer awaiting cystectomy and urinary diversion led to significantly improved functional outcomes (total distance walked, submaximal exercise test), gait speed, and self-reported QoL [39]. Conversely, for patients with intra-abdominal or thoracic cancer (colorectal, thoracic, hepatobiliary, urologic), a total-body exercise program including strength, aerobic, and flexibility training (1hr/day, 3x/week for less than 4 weeks) resulted in no significant difference in 6MWT, health related QoL (HRQoL), or in-hospital complications [44].

Home-based exercise therapy has also been evaluated for prehabiliation prior to cardiac surgery [37] (valve repair/replacement, CABG), Holmium laser enucleation of the prostate [38], and a variety of other major general surgeries [45]. Prior to undergoing a cardiac valve repair/replacement or CABG, patients (n=22) that participated in an individualized exercise program (balance and strength-training exercises) had significant improvement in clinical frailty score, 6MWT distance and speed, and Short Physical Performance Battery (SPPB) Protocol. Notably, the 6MWT was shown to be significantly associated with reduced hospital LOS [37]. However, home-based therapy programs prior to other general surgeries may not be as clearly beneficial. For patients undergoing Holmium laser enucleation of the prostate (n=70), dedicated 3-minute pelvic floor muscle therapy 3x/day for 28 days preoperatively resulted in significant reductions in postoperative urinary incontinence at 3 months and no difference at 3 days, 1 month, or 6 months postoperative compared to those only participating in this therapy postoperatively [38]. Though not significantly different at each measured time point, both the intervention and the control groups had a decreasing rate of urinary incontinence from 3 days to 6 months postoperative [38]. There was also no significant improvement in stamina or mobility compared to control group for patients undergoing a variety of different types of surgeries (colorectal, thoracic, urological, transplant, oncological, and vascular surgery, n=80), who participated in a 3-8 week supervised walking program [45]. Notably, this intervention resulted in an average increased daily step count of 879 ± 1720 [45]. Limitations of this study include a small sample size and heterogeneity in surgical procedures, so findings should be interpreted accordingly.

Nutrition Therapy

Of the six studies assessing unimodal nutritional prehabilitation, five (83%) [13,18,19,24,30] involved nutritional supplementation and one (17%) [36] assessed impact of calorie restriction. Sample sizes ranged from 48 to 175, and all interventions were home-based therapies. Of the five supplementation studies [13,18,19,24,30], four (80%) [13,18,19,24] were conducted with patients with gastrointestinal cancer (colorectal, hepatobiliary, pancreatic) awaiting resection, and one (20%) [30] involved patients undergoing TKA or THA. Supplementation for patients with cancer included an oral mixture consisting of arginine, omega-3 fatty acids and nucleotides [13,18], omega-3 fatty acids alone [19], and biolactis powder (living Lactobacillus casei strain Shirota and BBG-01- a living Bifidobacterium breve strain Yakult), as well as galactooligosaccharides. Supplementation for joint replacement was with iron and L-ascorbic acid [30]. These studies included both pre- and post-operative supplementation. Nutritional supplementation in patients with gastrointestinal cancer revealed significantly lower risk of surgical site infection and need for postoperative antibiotic therapy, shorter recovery time [13], and significantly increased levels of hemoglobin [30]. No significant difference in surgical complications or adverse events [18,19,24] were found compared to controls.

One study [36] evaluated the impact of calorie restriction (diets individualized to 60% of daily energy expenditure) in patients scheduled for elective cardiac surgery (n=82) and found a significant decrease in serum creatinine (suggesting an improvement in kidney health) in the calorie restricted group prior to surgery and a significant decrease in creatinine 48 hours post-operatively in calorie restricted males with body mass index (BMI) > 25 and chronic kidney disease stage 1. Though not significant, the overall incidence of post-operative acute kidney injury was lower in the calorie restricted (71.7%) compared to control (47.5%) group.

Cognitive Therapy

Vlisides et al. [46] studied a cognitive prehabiliation model in patients scheduled for surgery (non-cardiac, non-major vascular, or non-intracranial). In this RCT, patients (n=52) participated in a 7-day, home-based computer program designed to improve executive function, attention, working memory, and visuospatial processing, all of which have been implicated in delirium. There was no significant difference in delirium incidence or cognitive performance in either group throughout the study period. Notably, only 17% of patients completed the full 7 days of training, and 48% opted out of training, which may have impacted efficacy of intervention.

Characteristics and efficacy of multimodal prehabilitation

Thirteen intervention trials [14–17,20–23,25–27,41,43,47,48] have examined the efficacy of multimodal prehabilitation in patients with colorectal cancer (n=6) [14–16,20–22], gastric cancer (n=2) [25,26], pancreatic cancer (n=1) [23], lung cancer (n=1) [41], esophageal cancer (n=1) [27] prior to resection surgery, or in cancer or non-cancer patients undergoing major elective abdominal or thoracic surgeries (n=2) [43,47,48].

Multimodal prehabilitation in patients with colorectal cancer or abdominal aortic aneurysm

The efficacy of multimodal prehabilitation in patients with colorectal cancer or abdominal aneurysm (n=627) was examined in a single center study with a matched control group [20]. The prehabilitation group (n=267, mean duration: 39 days) received a home-based personalized exercise program (aerobic training, resistance training and respiratory muscle training), dietary instructions (e.g., minimum daily protein intake, caloric intake of a patient’s basal need, supplemental protein drinks if needed), geriatric interventions (e.g., delirium prevention), and intravenous iron injection if indicated. Compared to a matched controls who did not undergo prehabilitation (n=360), the multimodal intervention led to significantly greater reductions in the incidence of delirium, with a subgroup analysis showing the greatest reductions in physically impaired patients and those between 80 and 84 years of age.

In patients with colorectal cancer, a single-blind, parallel arm, superiority randomized trial (n=110) [16], and a nonrandomized sequential comparative prospective cohort study (n=81) [21] have been performed. In the first study [16], the multimodal prehabilitation (n=55, duration: 4 weeks) included a personalized, home-based, supervised exercise (aerobic training, resistance exercises and stretching), nutrition (target protein intake, potentially with protein supplementation), and psychological intervention (e.g., causes of perioperative anxiety, depression, counselling regarding smoking and alcohol cessation). The control group (n=55) received the identical multimodal intervention program after performed surgery in form of rehabilitation. Prehabilitation did not appear to reduce postoperative complications in frail patients with colorectal cancer. Furthermore, there were no significant between-group differences in other postoperative outcomes (e.g., LOS, emergency department visits, readmissions, walking capacity, generic health status, anxiety or depression). In the second study [21], the prehabilitation program called “Programme Enhanced Elderly Recovery” at Sengkang General Hospital (n=58, PEERS) prior to surgery included 3 weeks of oral nutrition supplementation, 3 weeks of resistance training, one geriatrician consultation (e.g., optimizing polypharmacy, confusion, incontinence), and one cardiovascular consult (e.g., transthoracic echocardiogram). The matched control group (n=23, non-PEERS) did not receive the prehabilitation program. The PEERS demonstrated a significantly earlier return to bowel function, shorter LOS (9 vs 11 days, p=0.01), and an improved QoL 6 months post-surgery compared to control group. There were no significant between-group differences in 30-day mortality, survival or morbidity defined as Clavien-Dindo grade III or more.

Finally, three pilot trials with number of participants ranging from 8 to 14 examined the feasibility of multimodal prehabilitation in patients with colorectal cancer [14,15,22]. The Fit for Surgery intervention (n=8, duration: ≥ 4 weeks) [14] included high-intensity interval training and resistance training in supervised individual training sessions, nutritional support (e.g., increasing bodyweight by drinking protein shakes, intake of a multivitamin tablet), and medical optimization (e.g., anemia, high intake of alcohol, smoking). The Better Exercise and Food, Better Recovery (BEFORE) (n=9, duration: 4 weeks) [22] consisted of an ambulatory supervised, personalized exercise training (strength and aerobic training) and three freshly prepared protein-rich meals. The Fit4SurgeryTV program (n=14, duration between 18-32 days) [15] included an elderly adapted, at-home, computer-supported strength training and two protein-rich meals. All three pilot trials [14,15,22] demonstrated that the prehabilitation programs were feasible in patients with colorectal cancer prior to resection surgery.

Multimodal prehabilitation in patients with esophageal, gastric or pancreatic cancer

In patients with esophageal and gastro-esophageal junctional cancer (n=38) [27], the multimodal, personalized, home-based PREPARE (Physical activity, Respiratory exercises, Eat well, Psychological well-being, Ask for medications, Remove bad habits, Enhanced recovery) for Surgery (duration: not specified) was examined. The motivational interviewing-based intervention involved weekly telephone calls with exercise therapists and nutritionists for goal setting related to aerobic and strength exercises and nutrition, respectively. There was a significant reduction of 60-day pulmonary complications (32% vs 68%, p=0.001) and post-operative pneumonia (26% vs 66%, p=0.001) in the PREPARE compared to control group. Additionally, there was a shorter LOS in the PREPARE compared with control group (10 vs 13 days, p=0.018).

In patients with gastric cancer and a clinical frailty score > 4 (n=15) [25], the efficacy of a nutrition and exercise intervention (NEI, median duration: 13 days) was examined. The intervention included a predefined daily caloric and protein intake based on ideal body weight (IBW), and an exercise program including walking and resistance training. There was a significantly shorter LOS (13 days vs 16 days, p=0.03) and improved mean of neutrophil lymphocyte ratio in the NEI compared to non-NEI group. However, there were no between-group differences in postoperative complications or nutrition markers (e.g., BMI, soft lean mass or skeletal muscle mass).

Finally two single-arm pilot trials either in patients with gastric cancer (n=22) [26] or patients with hepatopancreatobiliary cancer (n=19) [23] have been performed. In the first study [26], the efficacy of a multimodal prehabilitation intervention (mean duration: 16 days) including exercise training (handgrip and resistance training, walking) and nutritional intervention (e.g., optimization of total daily calorie and protein intake, and oral supplementation with leucine metabolite b-hydroxy-b-methylbutyrate) was examined prior to gastrectomy. In pre-post comparisons, total calorie and protein intake were significantly higher after the program than before. Furthermore, handgrip strength significantly increased after the program. Finally, in patient with hepatopancreatobiliary cancer [23], a prehabilitation team provided evaluation and services (mean duration: 131 days) for smoking and alcohol cessation, exercise training, anemia, blood sugar, nutrition, psychological aspects, advanced care planning, social services, and alternative therapies. Frailty, as assessed by Fried frailty criteria, improved significantly after prehabilitation. There were no differences found in functional status, physical performance, psychosocial assessments, nutrition, symptom severity, laboratory values or LOS after prehabilitation.

Multimodal prehabilitation in patients with lung cancer

We found that only one study that has evaluated the impact of multimodal prehabilitation in patients with lung cancer. In this trial, 216 patients with non-small cell lung cancer were randomized to receive usual care or a prehabilitation program (duration > 2-4 weeks) involving respiratory muscle training and breathing exercises, cardiovascular exercises, education (e.g., health education and smoking cessation), and pharmacologic treatment (e.g., bronchodilator therapy) [41]. In pre-post analyses, the intervention led to significant improvements in dyspnea scores, frailty index, and 6MWT. Finally, compared to a total of 60 patients who declined prehabilitation, the median LOS for participants in the prehabilitation arm was significantly shorter than those in the control arm (7 vs 9 days, p=0.03).

Multimodal prehabilitation prior to cancer- and non-cancer-related major surgeries

In patients planned for major abdominal and thoracic surgery (n=139) [43], the efficacy of a multimodal prehabilitation (duration 4 weeks) including home-based physical exercises with aerobic and resistance exercises, nutrition advice with protein supplementation (i.e., consuming 20 g of whey-protein before sleeping on the days of aerobic exercises), and anxiety reduction, was examined. The authors compared patients younger than 65 years to patients at age of 65 years or older. There were no between-group differences in 6MWT, LOS or mortality.

In a single-arm trial in patients with abdominal cancer (n=24), the efficacy of a 4-week, home-based prehabilitation program was evaluated. It included supervised personal blood restriction training and nutrition (supplement in a dry form combining whey protein, creatinine monohydrate, and L-citruline). In pre-post comparisons, 6MWT, SPPB, timed up and go, 5-chair stand test and physical component score of QoL were significantly improved (all p < 0.05) [47]. Furthermore, prehabilitation was associated with a shorter LOS (p=0.02) with 5.5 fewer days (4.7±2.1 vs 10.2±1.2 days) and decreased incidence of any complications (p=0.03) compared to abdominal cancer patients who underwent usual preoperative care (n=71) [48]. However, prehabilitation was not related to incidence of serious complications, readmission rate, changes in hand grip strength, fear of falling, the mental component of QoL, fasting serum concentrations of myostatin, follistatin, or growth hormone [47,48].

Discussion

This scoping review presents a summary of the current literature on unimodal and multimodal surgical prehabilitation in older and frail adults. We included 36 studies examining the efficacy of prehabilitation across a wide array of study populations. Most included studies examined the efficacy of unimodal (one intervention, n=21) prehabilitation, while fewer examined multimodal (at least two different interventions, n=15) prehabilitation programs. The most frequently studied populations were patients with gastrointestinal cancer, especially colorectal cancer (n=10), followed by patients with knee or hip osteoarthritis awaiting TKA or THA (n=8). Though the findings are mixed, surgical prehabilitation showed the potential to diminish postoperative functional decline in several vulnerable populations.

The most frequently studied unimodal prehabilitation was exercise therapy. In patients awaiting TKA [28,29,31,32] and THA [33], home-based and outpatient therapy center-based exercise training led to improvements in functional outcomes, strength, range of motion, and other outcomes (e.g., pain, depression, or cognition). In cancer patients awaiting a resection surgery, the evidence was mixed. For example, in patients with lung cancer, exercise training led to improved cardiopulmonary fitness (e.g., VO2 peak, max power, peak aerobic power) [40], decreased postoperative pulmonary complications, and reduced LOS [42]. In contrast, in patients with intra-abdominal or thoracic cancer, an exercise program did not impact 6MWT, HRQoL, or in-hospital complications [44]. There might be several explanations for the lack of evidence in this RCT. First, only 60% of study participants completed the prehabilitation program per protocol, which might have reduced the impact of prehabilitation [44]. Second, frail patients with cancer may lack adequate reserve to respond to prehabilitation, or at least may benefit from a longer duration of the presurgical intervention (e.g., > 4-5 weeks) [44]. In other populations (e.g., cardiac valve repair/replacement or CABG), exercise training was associated with significant improvements of frailty and 6MWT [37]. The second mostly examined unimodal prehabilitation was nutritional supplementation. Only studies in patients with gastrointestinal cancer revealed lower risk of surgical site infection and need for postoperative antibiotic therapy, shorter recovery time [13], and significantly increased levels of hemoglobin [30]. Other studies did not find a clinically beneficial impact of nutritional supplementation on surgical complications or other outcomes [18,19,24]. Finally, cognitive training did not impact incidence of delirium or cognitive performance in patients scheduled for surgery [46]. However, notably, the above-mentioned studies have small sample sizes, and the interventions differ considerably (e.g., duration, setting, frequency).

The multimodal prehabilitation programs included a variety of intervention components (e.g., exercise training, nutrition, psychological intervention or geriatric consultation), and their efficacy was mostly examined in patients with colorectal cancer with mixed evidence to support benefit of prehabilitation. In two studies, prehabilitation led to a significant reduction of delirium incidence [20], earlier return to bowel function, shorter LOS, and improved QoL [21]. In contrast, another study failed to show an effect of prehabilitation on postoperative complications, LOS or other outcomes (e.g., walking capacity, anxiety, depression). In patients with gastrointestinal cancer (e.g., gastric, esophageal or pancreatic cancer) prior to resection surgery, multimodal prehabilitation led to a significant reduction of pulmonary complications [27], LOS [25], and frailty [23]. In lung cancer patients, prehabilitation was showed to be effective in reduction of dyspnea, frailty, LOS, and improvements in 6MWT [41]. The duration, frequency, and location of the multimodal prehabilitation differs largely. This variation of the mode of intervention of multimodal prehabilitation as well as the different outcomes in addition to different diseases and patient populations make it problematic for making comparisons and would require a standardization for different study populations.

This review of the current literature provides a comprehensive summary of unimodal and multimodal surgical prehabilitation in older and frail patients. A wide range of presurgical interventions were discussed and gaps in the current literature were identified. Several limitations should be acknowledged. This is not a systematic review, and it is possible that additional studies examining the efficacy of surgical prehabilitation were not included. Additionally, the included studies are heterogenous with variation in disease, surgical procedure, and assessments. Lastly, only a few of the included studies are RCTs with sufficient power to detect between-group differences on the studied outcomes. Due to this paucity, non-randomized trials were included, and these inherently have a higher risk of bias.

Conclusions

Overall, the evidence is supportive of surgical prehabilitation in older and frail individuals. There is a need for adequately powered, randomized, controlled, assessor-blinded intervention trials to assess the benefit of prehabilitation in improving outcomes in older and frail patients prior to surgery. Exercise therapy and multimodal interventions addressing a range of intervention components are likely to be of greatest benefit in this patient group awaiting TKA, THA, and cancer-related resection surgery (e.g., due to colorectal, gastric or lung cancer). However, further evidence of the efficacy of prehabilitation is required.

Supplementary Material

eTable 1

eTable 1: Search terms utilized in search strategy

Data availability

The search strategies of the performed for this review are available upon request to the corresponding author.