Perioperative medicine training resources: U3M4: Exercise programs for surgical patients 

Abstract
In this article, we review the evidence underpinning the broader prehabilitation concept and the target behavioural and lifestyle risk factors including their perioperative impact and evidence for prehabilitation intervention. We also identify principles for delivering prehabilitation in practice, alongside lessons for the perioperative setting from well-established allied interventions; cardiac and pulmonary rehabilitation.

Abstract
Purpose of review: Advances in medical care have led to an increasing elderly population. Elderly individuals should be able to participate in society as long as possible. However, with an increasing age their adaptive capacity gradually decreases, specially before and after major life events (like hospitalization and surgery) making them vulnerable to reduced functioning and societal participation. Therapeutic exercise before and after surgery might augment the postoperative outcomes by improving functional status and reducing the complication and mortality rate.

Recent findings: There is high quality evidence that preoperative exercise in patients scheduled for cardiovascular surgery is well tolerated and effective. Moreover, there is circumstantial evidence suggesting preoperative exercise for thoracic, abdominal and major joint replacement surgery is effective, provided that this is offered to the high-risk patients. Postoperative exercise should be initiated as soon as possible after surgery according to fast-track or enhanced recovery after surgery principles.

Summary: The perioperative exercise training protocol known under the name 'Better in, Better out' could be implemented in clinical care for the vulnerable group of patients scheduled for major elective surgery who are at risk for prolonged hospitalization, complications and/or death. Future research should aim to include this at-risk group, evaluate perioperative high-intensity exercise interventions and conduct adequately powered trials.

Abstract
Reduced exercise capacity is associated with increased postoperative morbidity. Cardiopulmonary exercise testing variables can be used to risk stratify patients. This information can be used to help guide the choice of surgical procedure and to decide on the most appropriate postoperative care environment. Thus CPET can aid collaborative decision making and improve the process of informed consent. In the future, CPET may be combined with other risk predictors to improve outcome prediction. Furthermore early evidence suggests that CPET can be used to guide prehabilitation training programs, improving fitness and thereby reducing perioperative risk.

Abstract
Background: The certainty that prehabilitation improves postoperative outcomes is not clear. The objective of this umbrella review (i.e. systematic review of systematic reviews) was to synthesise and evaluate evidence for prehabilitation in improving health, experience, or cost outcomes.

Methods: We performed an umbrella review of prehabilitation systematic reviews. MEDLINE, Embase, Cochrane, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Joanna Briggs Institute's database, and Web of Science were searched (inception to October 20, 2020). We included all systematic reviews of elective, adult patients undergoing surgery and exposed to a prehabilitation intervention, where health, experience, or cost outcomes were reported. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. Primary syntheses of any prehabilitation were stratified by surgery type.

Results: From 1412 titles, 55 systematic reviews were included. For patients with cancer undergoing surgery who participate in any prehabilitation, moderate certainty evidence supports improvements in functional recovery. Low to very low certainty evidence supports reductions in complications (mixed, cardiovascular, and cancer surgery), non-home discharge (orthopaedic surgery), and length of stay (mixed, cardiovascular, and cancer surgery). There was low to very low certainty evidence that exercise prehabilitation reduces the risk of complications, non-home discharge, and length of stay. There was low to very low certainty evidence that nutritional prehabilitation reduces risk of complications, mortality, and length of stay.

Conclusions: Low certainty evidence suggests that prehabilitation may improve postoperative outcomes. Future low risk of bias, randomised trials, synthesised using recommended standards, are required to inform practice. Optimal patient selection, intervention design, and intervention duration must also be determined.

Abstract
Importance: Prehabilitation programs for patients undergoing orthopedic surgery have been gaining popularity in recent years. However, the current literature has produced varying results.

Objective: To evaluate whether prehabilitation is associated with improved preoperative and postoperative outcomes compared with usual care for patients undergoing orthopedic surgery.

Data sources: Bibliographic databases (MEDLINE, CINAHL [Cumulative Index to Nursing and Allied Health Literature], AMED [Allied and Complementary Medicine], Embase, PEDRO [Physiotherapy Evidence Database], and Cochrane Central Register of Controlled Trials) were searched for published trials, and the Institute for Scientific Information Web of Science, System for Information on Grey Literature in Europe, and European clinical trials registry were searched for unpublished trials from January 1, 2000, to June 30, 2022.

Study selection: Randomized clinical trials (RCTs) comparing prehabilitation with standard care for any orthopedic surgical procedure were included.

Data extraction and synthesis: Two independent reviewers screened trials. Data were pooled using a random-effects model. Recommendations were determined using the Grading of Recommendations Assessment, Development and Evaluation system and the study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline.

Main outcomes and measures: Pain, function, muscle strength, and health-related quality of life (HRQOL).

Results: Forty-eight unique trials involving 3570 unique participants (2196 women [61.5%]; mean [SD] age, 64.1 [9.1] years) were analyzed. Preoperatively, moderate-certainty evidence favoring prehabilitation was reported for patients undergoing total knee replacement (TKR) for function (standardized mean difference [SMD], -0.70 [95% CI, -1.08 to -0.32]) and muscle strength and flexion (SMD, 1.00 [95% CI, 0.23-1.77]) and for patients undergoing total hip replacement (THR) for HRQOL on the 36-item Short Form Health Survey (weighted mean difference [WMD], 7.35 [95% CI, 3.15-11.54]) and muscle strength and abduction (SMD, 1.03 [95% CI, 0.03-2.02]). High-certainty evidence was reported for patients undergoing lumbar surgery for back pain (WMD, -8.20 [95% CI, -8.85 to -7.55]) and moderate-certainty evidence for HRQOL (SMD, 0.46 [95% CI, 0.13-0.78]). Postoperatively, moderate-certainty evidence favoring prehabilitation was reported for function at 6 weeks in patients undergoing TKR (SMD, -0.51 [95% CI, -0.85 to -0.17]) and at 6 months in those undergoing lumbar surgery (SMD, -2.35 [95% CI, -3.92 to -0.79]). Other differences in outcomes favoring prehabilitation were of low to very low quality of evidence.

Conclusions and relevance: In this systematic review and meta-analysis of RCTs, moderate-certainty evidence supported prehabilitation over usual care in improving preoperative function and strength in TKR and HRQOL and muscle strength in THR, high-certainty evidence in reducing back pain, and moderate-certainty evidence in improving HRQOL in lumbar surgery. Postoperatively, moderate-certainty evidence supported prehabilitation for function following TKR at 6 weeks and lumbar surgery at 6 months. Prehabilitation showed promising results for other outcomes, although high risk of bias and heterogeneity affected overall quality of evidence. Additional RCTs with a low risk of bias investigating preoperative and postoperative outcomes for all orthopedic surgical procedures are required.

Abstract
There is a consistent relationship between physical activity, physical fitness, and health across almost all clinical contexts, including the perioperative setting. Physiological measurements obtained during physical exercise may be used to infer the risk of adverse outcome after major surgery. In particular, data obtained from perioperative cardiopulmonary exercise testing have an expanding role in perioperative care. Such information may be used to inform a variety of changes in clinical practice, including interventions that may reduce the risk of perioperative adverse events. Specifically, for patients undergoing major cancer surgery there is a complex interplay between different cancer treatments, including neoadjuvant therapies (chemo- and chemo- plus radiotherapy), surgery, and physical fitness, and the modulation of these relationships by perioperative exercise interventions. Preoperative cardiopulmonary exercise testing provides an objective evaluation of physical fitness and has been used to provide an individualized risk profile in order to guide collaborative decision-making, inform the consent process, characterize and optimize co-morbidities, and to triage patients to perioperative care. Furthermore, studies evaluating exercise interventions aimed at increasing preoperative exercise capacity have established that training improves physical fitness. However, to date, this literature is largely composed of feasibility and pilot studies with small sample sizes, which are in general underpowered to assess clinical outcomes. Adequately powered prospective multicentre studies are needed to characterize the most effective means of improving patient fitness before surgery and to evaluate the impact of such improvements on surgical and disease-specific (e.g. cancer) outcomes.

Abstract
Background: Chemotherapy offers cancer patients the potential benefits of improved mortality and morbidity but may cause detrimental outcomes due to adverse drug events (ADEs), some of which requiring time-consuming, resource-intensive and costly clinical management. To appropriately assess chemotherapy agents in an economic evaluation, ADE-related parameters such as the incidence, (dis)utility and cost of ADEs should be reflected within the model parameters. To date, there has been no systematic summary of the existing literature that quantifies the utilities of ADEs due to healthcare interventions in general and chemotherapy treatments in particular.

Objective: This review aimed to summarize the current evidence base of reported utility values for chemotherapy-related ADEs.

Methods: A structured electronic search combining terms for utility, utility valuation methods and generic terms for cancer treatment was conducted in MEDLINE and EMBASE in June 2011. Inclusion criteria were: (1) elicitation of utility values for chemotherapy-related ADEs and (2) primary data. Two reviewers identified studies and extracted data independently. Any disagreements were resolved by a third reviewer.

Results: Eighteen studies met the inclusion criteria from the 853 abstracts initially identified, collectively reporting 218 utility values for chemotherapy-related ADEs. All 18 studies used short descriptions (vignettes) to obtain the utility values, with nine studies presenting the vignettes used in the valuation exercises. Of the 218 utility values, 178 were elicited using standard gamble (SG) or time trade-off (TTO) approaches, while 40 were elicited using visual analogue scales (VAS). There were 169 utility values of specific chemotherapy-related ADEs (with the top ten being anaemia [34 values], nausea and/or vomiting [32 values], neuropathy [21 values], neutropenia [12 values], diarrhoea [12 values], stomatitis [10 values], fatigue [8 values], alopecia [7 values], hand-foot syndrome [5 values] and skin reaction [5 values]) and 49 of non-specific chemotherapy-related adverse events. In most cases, it was difficult to directly compare the utility values as various definitions and study-specific vignettes were used for the ADEs of interest.

Limitations: This review was designed to provide an overall description of existing literature reporting utility values for chemotherapy-related ADEs. The findings were not exhaustive and were limited to publications that could be identified using the search strategy employed and those reported in the English language.

Conclusions: This review identified wide ranges in the utility values reported for broad categories of specific chemotherapy-related ADEs. There were difficulties in comparing the values directly as various study-specific definitions were used for these ADEs and most studies did not make the vignettes used in the valuation exercises available. It is recommended that a basic minimum requirement be developed for the transparent reporting of study designs eliciting utility values, incorporating key criteria such as reporting how the vignettes were developed and presenting the vignettes used in the valuation tasks as well as valuing and reporting the utility values of the ADE-free base states. It is also recommended, in the future, for studies valuing the utilities of chemotherapy-related ADEs to define the ADEs according to the National Cancer Institute (NCI) definitions for chemotherapy-related ADEs as the use of the same definition across studies would ease the comparison and selection of utility values and make the overall inclusion of adverse events within economic models of chemotherapy agents much more straightforward.

Abstract
Backgrounds: There is mixed evidence on the value of preoperative cardiorespiratory exercise test (CPET) to predict postoperative outcomes in patients undergoing a cancer surgical procedure. The purpose of this review was to investigate the association between preoperative CPET variables and postoperative complications, length of hospital stay, and quality of life in patients undergoing cancer surgery.

Methods: A search was conducted on MEDLINE, Embase, AMED, and Web of science from inception to April 2020. Cohort studies investigating the association between preoperative CPET variables, including peak oxygen uptake (peak VO2), anaerobic threshold (AT), or ventilatory equivalent for carbon dioxide (VE/VCO2), and postoperative outcomes (complications, length of stay, and quality of life) were included. Risk of bias was assessed using the QUIPS tool. A random-effect model meta-analysis was performed whenever possible.

Results: Fifty-two unique studies, including 10,030 patients were included. Overall, most studies were rated as having low risk of bias. Higher preoperative peak VO2 was associated with absence of postoperative complications (mean difference [MD]: 2.28; 95% confidence interval [CI]: 1.26-3.29) and no pulmonary complication (MD: 1.47; 95% CI: 0.49-2.45). Preoperative AT and VE/VCO2 also demonstrated some positive trends. None of the included studies reported a negative trend.

Conclusions: This systematic review and meta-analysis demonstrated a significant association between superior preoperative CPET values, especially peak VO2, and better postoperative outcomes. The assessment of preoperative functional capacity in patients undergoing cancer surgery has the potential to facilitate treatment decision making.

Abstract
Despite calls for the routine implementation of pre-operative exercise programmes to optimise patient fitness before elective major surgery, there is no practical guidance for providing safe and effective exercise in this specific context. The following clinical guideline was developed following a review of the evidence on the effects of pre-operative exercise interventions. We developed a series of best-practice and, where possible, evidence-based statements to advise on patient care with respect to exercise training in the peri-operative period. These statements cover: patient selection for exercise training in surgical patients; integration of exercise training into multi-modal prehabilitation programmes; and advice on exercise prescription factors and follow-up. Although we acknowledge that further research is needed to identify the optimal exercise prescription in different clinical scenarios, we urge peri-operative teams to make use of these recommendations.

Abstract
Objective: To summarize the current evidence on the effects of preoperative exercise therapy in patients awaiting invasive surgery on postoperative complication rate and length of hospital stay.

Data sources: A primary search of relevant key terms was conducted in the electronic databases of PubMed, EMBASE, PEDro and CINAHL.

Review methods: Studies were included if they were controlled trials evaluating the effects of preoperative exercise therapy on postoperative complication rate and length of hospital stay. The methodological quality of included studies was independently assessed by two reviewers using the PEDro scale. Statistical pooling was performed when studies were comparable in terms of patient population and outcome measures. Results were separately described if pooling was not possible.

Results: Twelve studies of patients undergoing joint replacement, cardiac or abdominal surgery were included. The PEDro scores ranged from 4 to 8 points. Preoperative exercise therapy consisting of inspiratory muscle training or exercise training prior to cardiac or abdominal surgery led to a shorter hospital stay and reduced postoperative complication rates. By contrast, length of hospital stay and complication rates of patients after joint replacement surgery were not significantly affected by preoperative exercise therapy consisting of strength and/or mobility training.

Conclusion: Preoperative exercise therapy can be effective for reducing postoperative complication rates and length of hospital stay after cardiac or abdominal surgery. More research on the utility of preoperative exercise therapy and its long-term effects is needed as well as insight in the benefits of using risk models.

Abstract
Purpose: Improving cardiopulmonary reserve, or peak oxygen consumption(
˙
V
O2peak ), may reduce postoperative complications; however, this may be difficult to achieve between diagnosis and surgery. Our primary aim was to assess the efficacy of an approximate 14-session, preoperative high-intensity interval training(HIIT) program to increase
˙
V
O2peak by a clinically relevant 2 ml·kg-1 ·min-1 . Our secondary aim was to document clinical outcomes.

Methodology: In this prospective study, participants aged 45-85 undergoing major abdominal surgery were randomized to standard care or 14 sessions of HIIT over 4 weeks. HIIT sessions involved approximately 30 min of stationary cycling. Interval training alternated 1 min of high (with the goal of reaching 90% max heart rate at least once during the session) and low/moderate-intensity cycling. Cardiopulmonary exercise testing(CPET) measured the change in
˙
V
O2peak from baseline to surgery. Clinical outcomes included postoperative complications, length of stay(LOS), and Short Form 36 quality of life questionnaire(SF-36).

Results: Of 63 participants, 46 completed both CPETs and 50 completed clinical follow-up. There was a significant improvement in the HIIT group's mean ± SD
˙
V
O2peak (HIIT 2.87 ± 1.94 ml·kg1 ·min-1 vs standard care 0.15 ± 1.93, with an overall difference of 2.73 ml·kg1 ·min-1 95%CI [1.53, 3.93] p < 0.001). There were no statistically significant differences between groups for clinical outcomes, although the observed differences consistently favored the exercise group. This was most notable for total number of complications (0.64 v 1.16 per patient, p = 0.07), SF-36 physical component score (p = 0.06), and LOS (mean 5.5 v 7.4 days, p = 0.07).

Conclusions: There was a significant improvement in
˙
V
O2peak with a four-week preoperative HIIT program. Further appropriately powered work is required to explore the impact of preoperative HIIT on postoperative clinical outcomes.