Hemodynamic, ventilatory and gas exchange responses to exercise using a cycle ergometer and the incremental shuttle walk test in pregnant women.

BACKGROUND: Cardiovascular disease, including hypertension, in pregnant women is a leading cause of morbidity and mortality globally. The development of reference intervals for cardiovascular responses using exercising testing to measure oxygen utilisation (V̇O2) with cardiopulmonary exercise testing (CPET), and distances walked using the incremental shuttle walk test (ISWT), may be promising methods to assess and stratify pregnant women regarding their risk of adverse pregnancy outcomes, to encourage exercise during pregnancy, and to improve exercise prescriptions during pregnancy. We aimed to determine the reference intervals for V̇O2 at rest, anaerobic threshold (AT), and submaximal exercise using CPET, and the reference interval for the ISWT, to develop a correlation equitation that predicts submaximal V̇O2 from the distance walked in the ISWT, and to explore the relationship between hemoglobin (Hb) and ferritin concentration and V̇O2 at AT in women in second trimester. METHODS: After prospective IRB approval (HREC 15/23) and clinical trials registration (ANZCTR ACTRN12615000964516), and informed written consent, we conducted CPET and the ISWT according to international guidelines in a university associated tertiary referral obstetric and adult medicine hospital, in healthy pregnant women in second trimester (14 to 27 gestational weeks). Hemoglobin and ferritin concentrations were recorded from pathology results in the participants' medical records at the time of exercise testing. Adverse events were recorded. RESULTS: About 90 participants undertook CPET, 28 of which also completed the ISWT. The mean ± SD age and body mass index (BMI) were 32 ± 3.2 years, and 25 ± 2.7 kg/m2. Median (IQR) gestation was 23 (22-24) weeks. One in 4 women were 24 weeks or greater gestation. The reference intervals for V̇O2 at rest, AT, and submaximal exercise were 2.9 to 5.3, 8.1 to 20.7, and 14.1 to 30.5 mL/kg/min respectively. The reference interval for the ISWT was 218 to 1058 meters. The correlation equation to predict submaximal V̇O2 from the distance walked in the ISWT was submaximal V̇O2 (mL/kg/min) = 0.012*distance walked in ISWT (m) + 14.7 (95%CI slope 0.005-0.070, Pearson r = 0.5426 95%CI 0.2126-0.7615, P = .0029). Hemoglobin concentration was positively correlated with V̇O2 at AT (AT V̇O2 (mL/kg/min) = 0.08*Hb (g/L) + 4.9 (95%CI slope 0.0791-0.143, Pearson r = 0.2538 95%CI 0.049-0.438, P = .016). There was no linear association between ferritin and submaximal V̇O2 (Pearson r = 0.431 P = .697). There were no maternal or fetal complications. CONCLUSIONS: CPET and ISWT are safe and feasible in women in second trimester including those at or beyond 24 weeks gestation. We have established the reference interval for V̇O2 at rest, AT, and submaximal exercise by CPET, the reference interval for the distance walked for the ISWT, and a correlation equation to predict submaximal V̇O2 for use in clinical practice and research. Hemoglobin rather than ferritin is likely correlated with exercise capacity in pregnancy suggesting vigilance to correct lower hemoglobin levels may positively impact maternal health. CLINICAL TRIALS REGISTRY: The study was prospectively registered with the Australian and New Zealand Clinical Date of registration - 15/9/2015; Date of initial participant enrolment - 4/11/2015; Clinical trial identification number; ACTRN12615000964516; URL of the registration site - https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369216.

PRehabIlitatiOn with pReoperatIve exercise and educaTion for patients undergoing major abdominal cancer surgerY: protocol for a multicentre randomised controlled TRIAL (PRIORITY TRIAL).

BACKGROUND: Radical surgery is the mainstream treatment for patients presenting with advanced primary or recurrent gastrointestinal cancers; however, the rate of postoperative complications is exceptionally high. The current evidence suggests that improving patients' fitness during the preoperative period may enhance postoperative recovery. Thus, the primary aim of this study is to establish the effectiveness of prehabilitation with a progressive, individualised, preoperative exercise and education program compared to usual care alone in reducing the proportion of patients with postoperative in-hospital complications. The secondary aims are to investigate the effectiveness of the preoperative intervention on reducing the length of intensive care unit and hospital stay, improving quality of life and morbidity, and reducing costs. METHODS: This is a multi-centre, assessor-blinded, pragmatic, comparative, randomised controlled trial. A total of 172 patients undergoing pelvic exenteration, cytoreductive surgery, oesophagectomy, hepatectomy, gastrectomy or pancreatectomy will be recruited. Participants will be randomly allocated to prehabilitation with a preoperative exercise and education program (intervention group), delivered over 4 to 8 weeks before surgery by community physiotherapists/exercise physiologists, or usual care alone (control group). The intervention will comprise 12 to 24 individualised, progressive exercise sessions (including aerobic/anaerobic, resistance, and respiratory exercises), recommendations of home exercises (16 to 32 sessions), and daily incidental physical activity advice. Outcome measures will be collected at baseline, the week prior to surgery, during the hospital stay, and on the day of discharge from hospital, and 1 month and 1 months postoperatively. The primary outcome will be the development of in-hospital complications. Secondary outcomes include the length of intensive care unit and hospital stay, quality of life, postoperative morbidity and costs. DISCUSSION: The successful completion of this trial will provide robust and high-quality evidence on the efficacy of a preoperative community- and home-based exercise and education intervention on important postoperative outcomes of patients undergoing major gastrointestinal cancer surgery. TRIAL REGISTRATION: This trial was registered prospectively with the Australian New Zealand Clinical Trials Registry ( ACTRN12621000617864 ) on 24th May 2021.

Preoperative Cardiopulmonary Exercise Test Associated with Postoperative Outcomes in Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analyses.

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.

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: a secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study.

BACKGROUND: Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. METHODS: In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg-1 min-1 and peak oxygen consumption (VO2 peak) >16 ml kg-1 min-1, cut-points that represent a reduced risk of postoperative complications. RESULTS: Five questions were identified to have dominance in predicting AT>11 ml kg-1 min-1 and VO2 peak>16 ml.kg-1min-1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg-1.min-1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO2 peak>16 ml.kg-1.min-1 and VO2 peak<16 ml.kg-1.min-1. CONCLUSIONS: The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management.

Patient acceptance of prehabilitation for major surgery: an exploratory survey.

PURPOSE: Prehabilitation programs are effective in optimising patient's functional reserve prior to surgery and increasingly associated with reduced postoperative complications. However, acceptability of programs among patients is largely unknown. This study set out to explore the acceptability of prehabilitation from the perspective of patients awaiting major cancer surgery. METHODS: Adult patients awaiting major gastrointestinal and urological cancer surgeries were surveyed. Patients were excluded if they were unable to complete the survey due to language, intellectual impairment and/or visual/hearing deficit. The survey was designed to explore categories related to patient demographics, level of physical activity and perceived enablers and barriers to prehabilitation. RESULTS: One hundred and three participants presenting to a pre-anaesthesia clinic completed the survey over a 5-month period, with 83% response rate. Approximately, half of the respondents were female (55%) and were currently physically active (53%). Fewer than one third (30%) felt they completed 'enough exercise'. The majority of participants (83%) were unfamiliar with the concept of prehabilitation but two thirds (68%) were interested in such a program after explanation. The majority of participants (72%) indicated a strong preference to exercise in a home-based environment. Medical recommendation increased willingness to participate (p < 0.001), while program costs (p = 0.01) were potential barriers to participation. CONCLUSION: Patients are willing to participate in prehabilitation prior to major cancer surgery but practical barriers and facilitators should be considered when designing prehabilitation programs to maximise patient commitment to facilitate improved postoperative outcomes.

Implementing a telehealth prehabilitation education session for patients preparing for major cancer surgery.

BACKGROUND: Prehabilitation services assist patients in preparing for surgery, yet access to these services are often limited by geographical factors. Enabling rural and regional patients to access specialist surgical prehabilitation support with the use of telehealth technology has the potential to overcome health inequities and improve post-operative outcomes. AIM: To evaluate the current and likely future impact of a telehealth preoperative education package for patients preparing for major abdominal cancer surgery. METHODS: A telehealth alternative to a hospital based pre-operative education session was developed and implemented at a dedicated cancer hospital. Adult patients (≥18 years) scheduled for elective major cancer surgery were offered this telehealth alternative. Impact evaluation was conducted using the RE-AIM framework. RESULTS: To date, 35 participants have consented to participate in the study. Thirty-one participants attended the intervention; 24 (69%) residing in rural or regional areas. Twenty-four (77%) reported that if given a choice they would prefer the online session as opposed to attending the hospital in person. The majority (97%) reported they would recommend the intervention to others preparing for surgery. Session information was recalled by all 26 participants and 77% of participants reported acting on recommendations 2 weeks after the session. Lessons learnt and recommendations for providers implementing similar programs are reported. CONCLUSION: Telehealth alternatives to hospital based pre-operative education are well received by patients preparing for major cancer surgery. We make seven recommendations to improve implementation. Further evaluation of implementation strategies alongside clinical effectiveness in future studies is essential. TRIAL REGISTRATION: ACTRN12620000096954 , 04/02/2020.

A cross-sectional survey of Australian anesthetists' and surgeons' perceptions of preoperative risk stratification and prehabilitation.

PURPOSE: Preoperative fitness training has been listed as a top ten research priority in anesthesia. We aimed to capture the current practice patterns and perspectives of anesthetists and colorectal surgeons in Australia and New Zealand regarding preoperative risk stratification and prehabilitation to provide a basis for implementation research. METHODS: During 2016, we separately surveyed fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) and members of the Colorectal Society of Surgeons in Australia and New Zealand (CSSANZ). Our outcome measures investigated the responders' demographics, practice patterns, and perspectives. Practice patterns examined preoperative assessment and prehabilitation utilizing exercise, hematinic, and nutrition optimization. RESULTS: We received 155 responses from anesthetists and 71 responses from colorectal surgeons. We found that both specialty groups recognized that functional capacity was linked to postoperative outcome; however, fewer agreed that robust evidence exists for prehabilitation. Prehabilitation in routine practice remains low, with significant potential for expansion. The majority of anesthetists do not believe their patients are adequately risk stratified before surgery, and most of their colorectal colleagues are amenable to delaying surgery for at least an additional two weeks. Two-thirds of anesthetists did not use cardiopulmonary exercise testing as they lacked access. Hematinic and nutritional assessment and optimization is less frequently performed by anesthetists compared with their colorectal colleagues. CONCLUSIONS: An unrecognized potential window for prehabilitation exists in the two to four weeks following cancer diagnosis. Early referral, larger multi-centre studies focusing on long-term outcomes, and further implementation research are required.

RéSUMé: OBJECTIF: Le conditionnement physique préopératoire a été cité dans les dix priorités de recherche les plus importantes en anesthésie. Notre objectif était de déterminer quels étaient les habitudes actuelles de pratique ainsi que les perspectives des anesthésistes et des chirurgiens colorectaux en Australie et en Nouvelle-Zélande concernant la stratification préopératoire du risque et la préhabilitation afin de proposer un point de départ pour la recherche sur sa mise en œuvre. MéTHODE: Au cours de l'année 2016, nous avons soumis un questionnaire séparé aux membres du Collège australien et néozélandais des anesthésistes (ANZCA - Australian and New Zealand College of Anaesthetists) et aux membres de la Société colorectale des chirurgiens australiens et néozélandais (CSSANZ - Colorectal Society of Surgeons in Australia and New Zealand). Nos critères d'évaluation portaient sur les données démographiques, les habitudes de pratique et les perspectives des répondants. Les questions sur les habitudes de pratique touchaient à l'évaluation préopératoire et la préhabilitation fondée sur l'exercice physique et l'optimisation antianémique et nutritionnelle. RéSULTATS: Nous avons reçu 155 réponses d'anesthésistes et 71 réponses de chirurgiens colorectaux. Notre questionnaire a révélé que les deux spécialités reconnaissaient que la capacité fonctionnelle est liée au pronostic postopératoire; toutefois, moins de répondants étaient d'avis qu'il existe des données probantes fiables concernant la préhabilitation. Dans la pratique de routine, la préhabilitation demeure peu courante mais a le potentiel de prendre plus d'ampleur. La plupart des anesthésistes estiment que leurs patients ne sont pas stratifiés adéquatement en fonction de leur risque avant leur chirurgie, et la plupart de leurs collègues colorectaux sont ouverts à l'idée de retarder la chirurgie d'au moins deux semaines supplémentaires. Deux tiers des anesthésiologistes n'ont pas eu recours à un test d'effort cardiopulmonaire par manque d'accès à ce type d'examen. L'évaluation et l'optimisation antianémique et nutritionnelle sont moins fréquemment réalisées par les anesthésistes comparativement à leurs collègues colorectaux. CONCLUSION: Il existe une fenêtre potentielle mais non reconnue pour la mise en œuvre d'une préhabilitation au cours des deux à quatre semaines suivant l'annonce d'un diagnostic de cancer. Une prise en charge précoce par des spécialistes, des études multicentriques plus importantes s'intéressant aux pronostics à long terme et des travaux de recherche supplémentaires sur la mise en œuvre sont nécessaires.

Multimodal Prehabilitation Programs as a Bundle of Care in Gastrointestinal Cancer Surgery: A Systematic Review.

BACKGROUND: Prehabilitation reflects a proactive process of preoperative optimization undertaken between cancer diagnosis and definitive surgical treatment, with the intent of improving physiological capacity to withstand the major insult of surgery. Prehabilitation before GI cancer surgery is currently not widely adopted, and most research has focused on unimodal interventions such as exercise therapy, nutritional supplementation, and hematinic optimization. A review of the existing literature was undertaken to investigate the impact of multimodal prehabilitation programs as a "bundle of care." DATA SOURCE: A systematic literature search was performed utilizing Medline, PubMed, Embase, Cinahl, Cochrane, and Google Scholar databases. STUDY SELECTION: The quality of studies was assessed by using the Cochrane tool for assessing risk of bias (randomized trials) and the Newcastle-Ottawa Quality Assessment scale (cohort studies). INTERVENTION: Studies were chosen that involved pre-operative optimization of patients before GI cancer surgery. MAIN OUTCOMES: The primary outcome measured was the impact of prehabilitation programs on preoperative fitness and postoperative outcomes. RESULTS: Of the 544 studies identified, 20 were included in the qualitative analysis. Two trials investigated the impact of multimodal prehabilitation (exercise, nutritional supplementation, anxiety management). Trials exploring prehabilitation with unimodal interventions included impact of exercise therapy (7 trials), impact of preoperative iron replacement (5 trials), nutritional optimization (5 trials), and impact of preoperative smoking cessation (2 trials). Compliance within the identified studies was variable (range: 16%-100%). LIMITATIONS: There is a lack of adequately powered trials that utilize objective risk stratification and uniform end points. As such, a meta-analysis was not performed because of the heterogeneity in study design. CONCLUSION: Although small studies are supportive of multimodal interventions, there are insufficient data to make a conclusion about the integration of prehabilitation in GI cancer surgery as a bundle of care. Larger, prospective trials, utilizing uniform objective risk stratification and structured interventions, with predefined clinical and health economic end points, are required before definitive value can be assigned to prehabilitation programs.

Systematic Review and Meta-analysis of Objective Assessment of Physical Fitness in Patients Undergoing Colorectal Cancer Surgery.

BACKGROUND: Gas exchange-derived variables obtained from cardiopulmonary exercise testing allow objective assessment of functional capacity and hence physiological reserve to withstand the stressors of major surgery. Field walk tests provide an alternate means for objective assessment of functional capacity that may be cheaper and have greater acceptability, in particular, in elderly patients. OBJECTIVE: This systematic review evaluated the predictive value of cardiopulmonary exercise testing and field walk tests in surgical outcomes after colorectal surgery. DATA SOURCE: A systematic search was undertaken using Medline, PubMed, Embase, CINAHL, and PEDro. STUDY SELECTION: Adult patients who had cardiopulmonary exercise testing and/or field walk test before colorectal surgery were included. MAIN OUTCOME MEASURE: The primary outcomes measured were hospital length of stay and postoperative morbidity and mortality. RESULTS: A total of 7 studies with a cohort of 1418 patients who underwent colorectal surgery were identified for inclusion in a qualitative analysis. Both pooled oxygen consumption at anaerobic threshold (range, 10.1-11.1 mL·kg·min) and peak oxygen consumption (range, 16.7-18.6 mL·kg·min) were predictive of complications (OR for anaerobic threshold, 0.76; 95% CI, 0.66-0.85, p<0.0001; OR for peak oxygen consumption, 0.76; 95% CI, 0.67-0.85, p<0.0001). Patients had significant increased risk of developing postoperative complications if their anaerobic threshold was below this cut point (p<0.001). However, it was not predictive of anastomotic leak (p = 0.644). Shorter distance (<250 m) walked in incremental shuttle walk test, lower anaerobic threshold, and lower peak oxygen consumption were associated with prolonged hospital length of stay, which was closely related to the development of complications. CONCLUSIONS: Variables derived from cardiopulmonary exercise testing are predictive of postoperative complications and hospital length of stay. Currently, there are insufficient data to support the predictive role of the field walk test in colorectal surgery.

Comparison of Duke Activity Status Index with cardiopulmonary exercise testing in cancer patients.

PURPOSE: The Duke Activity Status Index (DASI), a patient-administered questionnaire, is used to quantify functional capacity in patients undergoing cancer surgery. METHODS: This retrospective cohort study assessed whether the DASI was accurate in predicting peak oxygen consumption (pVO2) that was objectively measured using cardiopulmonary exercise testing (CPET) in 43 consecutive patients scheduled for elective major cancer surgery at a tertiary cancer centre. The primary outcome measured the limits of agreement between DASI-predicted pVO2 and actual measured pVO2. RESULTS: The study population was elderly (median 63 years, interquartile range 18), 58% were male, with the majority having intraabdominal cancer surgery. Although the DASI scores were statistically related to the measured pVO2 (N = 43, adjusted R2 = 0.20, p = 0.002), both the bias (8 ml kg- 1 min- 1) and 95% limits of agreement (19.5 to - 3.4 ml kg- 1 min- 1) between the predicted and measured pVO2 were large. Using some of the individual components, recalibrating the intercept and regression coefficient of the total DASI score did not substantially improve its ability to predict the measured pVO2. CONCLUSION: In summary, both the limits of agreement and bias between the measured and DASI-predicted pVO2 were substantial. The DASI-predicted pVO2 based on patient's assessment of their functional status could not be considered a reliable surrogate of measured pVO2 during CPET for the population of patients pending major cancer surgery and cannot, therefore, be used as a triage tool for referral to CPET centres for objective risk assessment.

Evaluation of Reliability of MYZONE MZ-3 Heart Rate Monitor: A Study for the Future of Telephysiotherapy for Preoperative Prehabilitation in Cancer Patients.

BACKGROUND: There are a number of commercially available heart rate (HR) monitors on the market. The reliability of these monitors has had varying results. To the best of our knowledge, there are no telemonitoring services utilizing these devices for perioperative prehabilitation services for patients undergoing major surgery. The goal of this study is to pilot the MYZONE® MZ-3 HR monitor to assess its level of reliability to provide a feasible telephysiotherapy prehabilitation service through prescription-based exercise programs to patients presenting for major cancer surgery within our leading oncological health service. MATERIALS AND METHODS: Paired HR data from each participant were captured and analyzed using a Bland-Altman plot. RESULTS: Seven healthy participants were included in the study with a total number of paired HR data points of 1,928. The bias (mean difference) between electrocardiogram and the MYZONE MZ-3 was 0.4 beats per minute (bpm) with an adjusted 95% limits of agreement of -4.5 to 5.3 bpm. CONCLUSION: The commercially available MYZONE MZ-3 HR monitor is a reliable tool for delivering telephysiotherapy to patients undergoing major cancer surgery. Further studies are needed to validate its use in this setting.

Structured exercise program prior to major cancer surgery improves cardiopulmonary fitness: a retrospective cohort study.

PURPOSE: To determine if cardiopulmonary exercise testing (CPET) was useful in predicting response to exercise in cancer patients preoperatively. A secondary aim was to explore if exercise was associated with improved postoperative outcomes. METHODS: A retrospective cohort study was performed on consecutive cancer patients from 2012 to 2014, referred for exercise prehabilitation and had two CPET preoperatively. RESULTS: Twenty-six patients were analysed. There was a significant overall increase in oxygen uptake at anaerobic threshold (AT) from 10.4 to 11.6 ml kg(-1) min(-1) (ΔAT = 1.2 ± 3.0 ml kg(-1) min(-1) [9 %]; p = 0.046); peak oxygen uptake (pVO2) from 16.0 to 17.7 ml kg(-1) min(-1) (ΔpVO2 = 1.7 ± 2.4 ml kg(-1) min(-1) [9 %]; p = 0.002); and pVO2/BSA from 658 to 726 ml min(-1) m(-2); (ΔpVO2/BSA = 68 ± 112.3 mL min(-1) m(2) [10 %]; p = 0.004). Fifty percent of patients were responders to exercise, defined as having >10 % increase in AT. Responders had a median increase in AT of 26 % [IQR 7 %, 45 %] with an absolute increase in AT of 2.5 ml kg(-1) min(-1) [IQR 1.1, 3.9] (p = 0.002) and a median increase in pVO2 of 22 % [IQR 11.5, 32.5 %] with an absolute increase in pVO2 of 3.8 ml.kg(-1).min(-1) [IQR 2.0, 5.7] (p < 0.001). Responders were more likely to have a lower baseline AT (9.1 ml kg(-1) min(-1); p = 0.002). CONCLUSIONS: Exercise improved cardiorespiratory fitness prior to major cancer surgery. Not all patients responded the same, with only 50 % of the study cohort being responders to exercise. A low AT, pVO2 and ratio of AT/pVO2 at baseline were good predictors of response to exercise, with a tendency for responders to suffer fewer major postoperative complications.

Neuraxial Anesthesia Reduces Lymphatic Flow: Proof-of-Concept in First In-Human Study.

Dilation of lymphatic vessels may contribute to iatrogenic dissemination of cancer cells during surgery. We sought to determine whether neuraxial anesthesia reduces regional lymphatic flow. Using nuclear lymphoscintigraphy, 5 participants receiving spinal anesthesia for brachytherapy had lower extremity lymph flow at rest compared with flow under conditions of spinal anesthesia. Six limbs were analyzed. Four limbs were excluded because of failure to demonstrate lymph flow (1 patient, 2 limbs), colloid injection error (1 limb), and undiagnosed deep vein thrombosis (1 limb). All analyzed limbs showed reduced lymph flow washout from the pedal injection site (range 62%-100%) due to neuraxial anesthesia. Lymph flow was abolished in 3 limbs. We report proof-of-concept that neuraxial anesthesia reduces lymphatic flow through a likely mechanism of sympathectomy.

Exercise capacity prior to major cancer surgery: A cross-sectional observational study of the validity of the 6-minute walk and 30-second sit-to-stand tests.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is the gold standard for measuring exercise capacity, however, it is resource intensive and has limited availability. This study aimed to determine: 1) the association between the 6-min walk test (6MWT) and the 30-s sit-to-stand test (30STS) with CPET peak oxygen uptake (VO2peak) and anaerobic threshold (AT) and 2) 6MWT and 30STS cut points associated with a higher risk of postoperative complications. METHODS: A cross-sectional study, retrospectively analyzing data collected from a tertiary cancer center over a 23-month period. Measures included CPET VO2peak and AT, 6MWT and 30STS test. Correlations were used to characterize relationships between variables. Receiver operating characteristic curve analyses determined 6MWT and 30STS cut points that aligned with CPET variable cut points. RESULTS: Note that, 156 participants were included. The 6MWT and 30STS displayed moderate correlations with VO2peak, rho = 0.65, p = 0.01 and rho = 0.52, p < 0.005 respectively. Fair correlations were observed between AT and 6MWT (rho = 0.36, p = 0.01) and 30STS (rho = 0.41, p < 0.005). The optimal cut points to identify VO2peak < 15 mL/kg/min were 493.5 m on the 6MWT and 12.5 stands on the 30STS test and for AT < 11 mL/kg/min were 506.5 m on the 6MWT and 12.5 stands on the 30STS test. CONCLUSION: Both the 6MWT and 30STS test could be used as alternative tools for measuring exercise capacity preoperatively in the cancer setting where CPET is not available. A range of 6MWT and 30STS cut points, according to sensitivity and specificity levels, may be used to evaluate risk of postoperative outcomes.

Evaluating a Remotely Delivered Cardio-Oncology Rehabilitation Intervention for Patients With Breast Cancer (REMOTE-COR-B): Protocol for a Single-Arm Feasibility Trial.

BACKGROUND: Exercise rehabilitation is a promising strategy for reducing cardiovascular disease risk among patients with breast cancer. However, the evidence is primarily derived from programs based at exercise centers with in-person supervised delivery. Conversely, most patients report a preference for home-based rehabilitation. As such, there is a clear need to explore strategies that can provide real-time supervision and coaching while addressing consumer preferences. Evidence from cardiac rehabilitation has demonstrated the noninferiority of a smartphone-based telerehabilitation approach (REMOTE-CR) to improve cardiorespiratory fitness in people with cardiovascular disease compared to a center-based program. OBJECTIVE: This study aims to assess the feasibility, safety, and preliminary efficacy of the REMOTE-CR program adapted for patients with breast cancer at risk of cardiotoxicity (REMOTE-COR-B). We will also assess the satisfaction and usability of REMOTE-COR-B. METHODS: We will conduct a single-arm feasibility study of the REMOTE-COR-B program among patients with stage I-III breast cancer who are at risk of cardiotoxicity (taking treatment type and dose, as well as other common cardiovascular disease risk factors into account) and who are within 24 months of completing primary definitive treatment. Participants (target sample size of 40) will receive an 8-week smartphone-based telerehabilitation exercise program involving remotely delivered real-time supervision and behavior change support. The platform comprises a smartphone and wearable heart rate monitor, as well as a custom-built smartphone app and web application. Participants will be able to attend remotely monitored exercise sessions during set operating hours each week, scheduled in both the morning and evening. Adherence is the primary outcome of the trial, assessed through the number of remotely monitored exercise sessions attended compared to the trial target (ie, 3 sessions per week). Secondary outcomes include additional trial feasibility indicators (eg, recruitment and retention), safety, satisfaction, and usability, and objective and patient-reported efficacy outcomes (cardiovascular fitness, quality of life, fatigue, self-reported exercise, self-efficacy, habit strength, and motivation). Adherence, feasibility, and safety outcomes will be assessed during the intervention period; intervention satisfaction and usability will be assessed post intervention; and objective and patient-reported efficacy outcomes will be assessed at baseline, post intervention (2-month postbaseline assessment), and at follow-up (5-month postbaseline assessment). RESULTS: Recruitment for this trial commenced in March 2023, and 7 participants had been recruited as of the submission of the manuscript. The estimated completion date for the project is October 2024, with results expected to be published in mid-2025. CONCLUSIONS: The REMOTE-COR-B intervention is a novel and promising approach to providing exercise therapy to patients with breast cancer at risk of cardiotoxicity who have unique needs and heightened safety risks. This project will provide important information on the extent to which this approach is satisfactory to patients with breast cancer, safe, and potentially effective, which is necessary before larger-scale research or clinical projects. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621001557820; www.anzctr.org.au/ACTRN12621001557820.aspx. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53301.

End-tidal carbon dioxide in the early phase of cardiopulmonary exercise testing prior to major colorectal cancer surgery associates with postoperative outcome.

BACKGROUND: Cardiopulmonary exercise testing (CPET) objectively informs preoperative risk stratification prior to major surgery. CPET facilities are resource intensive and therefore more cost-effective triage methods are desirable for scalability. We tested two dynamic CPET parameters (end-tidal CO2 (PetCO2) and heart rate (HR)) to early phase exercise and resting diffusion capacity (DLCO) as potential point of care assessments that could be used outside of formal CPET testing facilities. METHODS: We conducted a retrospective cohort study including 84 patients who underwent CPET prior to elective major abdominal cancer surgery. Data were analyzed for PetCO2 and HR in response to early phase (2 minutes) exercise as well as resting DLCO against postoperative complications and two-year survival. Complications were classified according to Clavien-Dindo classification into less severe and severe (CD>IIIb) grades. Optimal cut points for predicting outcomes were determined using the Youden Index of receiver operating characteristic (ROC) curves. Multivariate regression modeling including both logistic and Cox proportional-hazards model adjusted to age and comorbidity burden was used to analyse the association between the selected parameters and postoperative outcomes. RESULTS: PetCO2, in response to two minutes of loaded exercise was higher in survivors than in non-survivors (median (IQR) 40.0 (4.2) mmHg vs. 34.5 (5.2) mmHg, P<0.001). There was no association between chronotropic response and postoperative outcome. The optimal cut point for predicting postoperative complications and survival was 38 mmHg and 37.1 mmHg for PetCO2, respectively. Low PetCO2 was associated with considerably lower odds of survival (OR 0.12; 95% CI 0.03, 0.47; P=0.003) and additionally increased odds of severe postoperative complications (OR 6.77; 95% CI 1.45, 38.4; P=0.019). Reduced age-predicted DLCO% <80% was associated with increased mortality (HR 5.27; 95% CI 1.09, 25.5; P=0.039). CONCLUSIONS: Assessment of DLCO at rest and dynamic assessment of PetCO2 during the early phase of exercise may potentially be developed as inexpensive point-of-care triage tools to scale objective preoperative risk assessment.

Sex-related differences in functional capacity and its implications in risk stratification before major non-cardiac surgery: a post hoc analysis of the international METS study.

Background: Poor functional capacity has been identified as an important modifiable risk factor for postoperative complications. Cardiopulmonary exercise testing (CPET) provides objective parameters of functional capacity (e.g., oxygen consumption at peak exercise, peak VO2), with significant prognostication for postoperative complications. However, sex-specific thresholds for functional capacity to predict surgical risk are yet to be established. Therefore, we performed a post hoc analysis of the international, multicentre, prospective observational METS (Measurement of Exercise Tolerance before Surgery) study to evaluate if sex-specific thresholds of peak VO2 improve risk prediction of postoperative complications. Methods: We undertook a post hoc analysis (HREC/71824/PMCC) of the METS study, which was performed between March 2013 and March 2016. We investigated whether sex-specific differences exist for CPET-derived parameters and associated thresholds for predicting postoperative complications in this large cohort of patients that had major non-cardiac surgery (n = 1266). Logistic regression models were analyzed for the association of low peak VO2 with moderate-to-severe in-hospital postoperative complications. Optimal sex-specific peak VO2 thresholds were obtained by maximizing the Youden index of receiver operating characteristic (ROC) curves. Finally, multivariable logistic regression models tested the resulting sex-specific thresholds against the established non-sex-specific peak VO2 threshold (14 mL kg-1 min-1) adjusted for clinically relevant features such as comorbidities and surgical complexity. Models were evaluated by bootstrapping optimism-corrected area under the ROC curve and the net reclassification improvement index (NRI). Findings: Female patients (n = 480) had a lower mean (SD) peak VO2 than males (16.7 (4.9) mL kg-1 min-1 versus 21.2 (6.5) mL kg-1 min-1, p < 0.001) and a lower postoperative complication rate (10.4% versus 15.3%; p = 0.018) than males (n = 786). The optimal peak VO2 threshold for predicting postoperative complications was 12.4 mL kg-1 min-1 for females and 22.3 mL kg-1 min-1 for males, respectively. In the multivariable regression model, low non-sex-specific peak VO2 did not independently predict postoperative complications. In contrast, low sex-specific peak VO2 was an independent predictor of postoperative complications (OR 2.29; 95% CI: 1.60, 3.30; p < 0.001). The optimism-corrected AUC-ROC of the sex-specific model was higher compared with the non-sex-specific model (0.73 versus 0.7; DeLong's test: p = 0.021). The sex-specific model classified 39% of the patients more correctly than the baseline model (NRI = 0.39; 95% CI: 0.24, 0.55). In contrast, the non-sex-specific model only classified 9% of the patients more correctly when compared against the baseline model (NRI = 0.09; 95% CI: -0.04, 0.22). Interpretation: Our data report sex-specific differences in preoperative CPET-derived functional capacity parameters. Sex-specific peak VO2 thresholds identify patients at increased risk for postoperative complications with a higher discriminatory ability than a sex-unspecific threshold. As such, sex-specific threshold values should be considered in preoperative CPET to potentially improve risk stratification and to guide surgical decision-making, including eligibility for surgery, preoperative optimization strategies (prehabilitation) or seeking non-surgical options. Funding: There was no funding for the present study. The original METS study was funded by Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

Prehabilitation in high-risk patients scheduled for major abdominal cancer surgery: a feasibility study.

BACKGROUND: Patients presenting for major surgery with low cardiorespiratory fitness (deconditioning) and other modifiable risk factors are at increased risk of postoperative complications. This study investigated the feasibility of delivering prehabilitation in high-risk patients scheduled for major abdominal cancer surgery. METHODS: Eligible patients in this single-center cohort study included patients with poor fitness (objectively assessed by cardiopulmonary exercise testing, CPET) scheduled for elective major abdominal cancer surgery. Patients were recruited to participate in a prehabilitation program that spanned up to 6 weeks pre-operatively and comprised aerobic and resistance exercise training, breathing exercise, and nutritional support. The primary outcome assessed pre-specified feasibility targets: recruitment >70%, retention >85%, and intervention adherence >70%. Secondary outcomes were assessed for improved pre-operative functional status and health-related quality of life and for postoperative complications. RESULTS: Eighty-two (34%) out of 238 patients screened between April 2018 and December 2019 were eligible for recruitment. Fifty (61%) patients (52% males) with a median age of 71 (IQR, 63-77) years participated in the study. Baseline oxygen consumption the at anaerobic threshold and at peak exercise (mean±SD: 9.8±1.8 and 14.0±2.9 mL/kg/min, respectively) confirmed the deconditioned state of the study cohort. The retention rate within the prehabilitation program was 84%, with 42 participants returning for repeat CPET testing. While >60% of participants preferred to do home-based prehabilitation, adherence to the intervention was low-with only 12 (28%) and 15 (35%) of patients having self-reported compliance >70% with their exercise prescriptions. CONCLUSION: Our prehabilitation program in high-risk cancer surgery patients did not achieve pre-specified targets for recruitment, retention, and self-reported program adherence. These findings underpin the importance of implementation research and strategies for the prehabilitation programs in major surgery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12620000073909 ) retrospectively registered.