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The Content of Pre-habilitative Interventions for Patients Undergoing Repair of Abdominal Aortic Aneurysms and Their Effect on Post-Operative Outcomes: A Systematic Review

Open ArchivePublished:March 04, 2021DOI:https://doi.org/10.1016/j.ejvs.2021.01.043

      Objective

      Patients requiring abdominal aortic aneurysm (AAA) repair are at risk of post-operative complications due to poor pre-operative state. Pre-habilitation describes the enhancement of functional capacity and tolerance to an upcoming physiological stressor, intended to reduce those complications. The ability to provide such an intervention (physical, pharmacological, nutritional, or psychosocial) between diagnosis and surgery is a growing interest, but its role in AAA repair is unclear. This paper aimed to systematically review existing literature to better describe the effect of pre-habilitative interventions on post-operative outcomes of patients undergoing AAA repair.

      Data sources

      EMBASE and Medline were searched from inception to October 2020. Retrieved papers, systematic reviews, and trial registries were citation tracked.

      Review methods

      Randomised controlled trials (RCTs) comparing post-operative outcomes for adult patients undergoing a period of pre-habilitation prior to AAA repair (open or endovascular) were eligible for inclusion. Two authors screened titles for inclusion, assessed risk of bias, and extracted data. Primary outcomes were post-operative 30 day mortality, composite endpoint of 30 day post-operative complications, hospital length of stay (LOS), and health related quality of life (HRQL) outcomes. The content of interventions was extracted and a narrative analysis of results undertaken.

      Results

      Seven RCTs with 901 patients were included (three exercise based, two pharmacological based, and two nutritional based). Risk of bias was mostly unclear or high and the clinical heterogeneity between the trials precluded data pooling for meta-analyses. The quality of intervention descriptions was highly variable. One exercise based RCT reported significantly reduced hospital LOS and another improved HRQL outcomes. Neither pharmacological nor nutritional based RCTs reported significant differences in primary outcomes.

      Conclusion

      There is limited evidence to draw clinically robust conclusions about the effect of pre-habilitation on post-operative outcomes following AAA repair. Well designed RCTs, adhering to reporting standards for intervention content and trial methods, are urgently needed to establish the clinical and cost effectiveness of pre-habilitation interventions.

      Keywords

      This study provides a review of current evidence investigating pre-habilitation in patients undergoing abdominal aorta aneurysm (AAA) repair and its effects on post-operative outcomes. Although pre-habilitation has potential to improve clinical and health related quality of life outcomes, the limited and heterogenous state of current literature precludes conclusive recommendations for future practice. The contents of included interventions were analysed and found to be generally inadequately described according to existing reporting standards. More high quality trials, conforming to an urgently needed set of core outcomes and reporting standards, are required to best inform the clinical and cost effectiveness of pre-habilitation for AAA repair.

      Introduction

      Abdominal aortic aneurysm (AAA) is a permanent, focal, full thickness dilatation of the abdominal aorta (luminal diameter ≥ 3.0 cm) with the risk of AAA rupture increasing with diameter. An anteroposterior diameter of 5.5 cm is typically the threshold at which open or endovascular aneurysm repair (EVAR) is offered.
      The risk factors predisposing to AAA development are also those predicting morbidity and mortality after surgery, with an estimated 17% of people referred with AAA deemed unsuitable for surgery. Attitudes towards the use of EVAR for patients deemed unfit for open repair are changing due to potentially worse long term morbidity and mortality.

      Overview. Abdominal aortic aneurysm: diagnosis and management. Guidance. NICE. Available at: https://www.nice.org.uk/guidance/ng156 [Accessed 7 March 2020].

      ,
      • Sweeting M.J.
      • Patel R.
      • Powell J.T.
      • Greenhalgh R.M.
      Endovascular repair of abdominal aortic aneurysm in patients physically ineligible for open repair.
      As such, there is an increasing need to improve this cohort’s pre-operative health.
      The period between AAA diagnosis and repair is a potential window for patient optimisation. Pre-habilitation describes the process of enhancing a patient’s functional capacity to improve their tolerance for an impending physiological stressor, aiming to improve peri- and post-operative outcomes.
      • Carli F.
      • Charlebois P.
      • Stein B.
      • Feldman L.
      • Zavorsky G.
      • Kim D.J.
      • et al.
      Randomized clinical trial of pre-habilitation in colorectal surgery.
      A systematic review by Kato et al.
      • Kato M.
      • Kubo A.
      • Green F.N.
      • Takagi H.
      Meta-analysis of randomized controlled trials on safety and efficacy of exercise training in patients with abdominal aortic aneurysm.
      in 2019 investigated the safety of exercise training compared with usual care for patients with AAA (≥ 3cm). This review of seven trials (489 patients) concluded that exercise training was safe (adverse cardiac event rate during exercise training 0.8%, 95% confidence interval (CI) 0.2% – 3.1%), with no reports of AAA rupture. Significant improvements in recognised predictors of short and long term survival after elective AAA (pre-operative peak oxygen consumption and anaerobic threshold) in favour of exercise were also observed.
      Pre-habilitation can also be a complex intervention, including pharmacological, nutritional, and psychosocial modalities. Cancer management pathways encourage this multi-modal approach for pre-operative optimisation,

      Principles and guidance for pre-habilitation – Macmillan Cancer Support. Available at: https://www.macmillan.org.uk/about-us/health-professionals/resources/practical-tools-for-professionals/pre-habilitation.html [Accessed 7 March 2020].

      but recent systematic reviews,
      • Thomas G.
      • Tahir M.R.
      • Bongers B.C.
      • Kallen V.L.
      • Slooter G.D.
      • van Meeteren N.L.
      Pre-habilitation before major intra-abdominal cancer surgery: a systematic review of randomised controlled trials.
      ,
      • Treanor C.
      • Kyaw T.
      • Donnelly M.
      An international review and meta-analysis of pre-habilitation compared to usual care for cancer patients.
      of randomised controlled trials (RCTs) concluded that more high quality studies were needed to confirm their benefits amongst various patient groups (e.g., level of risk and cancer type). Furthermore, a recent mixed methods analysis,
      • Goodwin V.A.
      • Hill J.J.
      • Fullam J.A.
      • Finning K.
      • Pentecost C.
      • Richards D.A.
      Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis.
      suggests that RCTs with poor rehabilitative intervention development are less likely to report treatment success. The quality and effects of such interventions prior to elective AAA repair have not been reviewed previously.
      Current national and international guidelines,

      Overview. Abdominal aortic aneurysm: diagnosis and management. Guidance. NICE. Available at: https://www.nice.org.uk/guidance/ng156 [Accessed 7 March 2020].

      ,
      • Wanhainen A.
      • Verzini F.
      • van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      European Society for Vascular Surgery 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      ,
      • Chaikof E.L.
      • Dalman R.L.
      • Eskandari M.K.
      • Jackson B.M.
      • Lee W.A.
      • Mansour M.A.
      • et al.
      The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.
      highlight a lack of literature examining AAA pre-operative optimisation. This study aimed to systematically review the content of pre-habilitative interventions for patients undergoing AAA repair and their effect on post-operative outcomes to inform future studies and the pre-operative management in this population.

      Materials and methods

      This systematic review was registered prospectively on PROSPERO (CRD42019157759) and was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

      Data searches and sources

      A literature search was performed using EMBASE (1947 to October 2020) and Medline (1946 to October 2020) (see Supplementary information). PROSPERO, the ClinicalTrials.gov registry, Cochrane database, and the WHO International Clinical Trials Registry Platform were searched for active and unpublished trials. References from relevant papers were reviewed to identify other relevant trials and papers describing study protocols. Further searches were run in Google scholar to identify any trials, or companion papers, missing from the original searches. The search was limited to the English language.

      Study selection

      RCTs investigating the effect of one or more pre-habilitative interventions compared with usual care or placebo, on the post-operative outcomes of patients undergoing elective AAA repair (open or EVAR) were included. Studies including participants at least 18 years old, diagnosed with an AAA requiring repair, with any level of risk of post-operative mortality were eligible for inclusion. Eligible interventions included physical exercise, psychosocial, nutritional, or pharmacological interventions designed to improve an individual’s physical or mental health in the period between identifying the need for repair and the operation. Since an objective of this study was to assess the content of these pre-habilitative interventions no further selection criteria, such as minimum intervention duration, were set. Interventions restricted to the peri-operative period, including those administered as part of the direct work up for surgery (24 hours prior to operation), were excluded. Studies could include one of the pre-operative interventions listed above within the standard care as long as both intervention and control groups were in receipt of usual care, and the intervention tested the direct effect of another intervention of interest provided in addition to usual care.
      Trials reporting at least one of the post-operative clinical outcomes (Table 1) were eligible for inclusion. Similar to intervention selection, no minimum follow up time or further criteria were set.
      Table 1Primary and secondary outcomes of interest for randomised controlled trials comparing post-operative outcomes for adult patients undergoing a period of pre-habilitation prior to abdominal aortic aneurysm repair
      Primary outcomesSecondary outcomes
      Post-operative 30 day mortalityAdherence to the intervention
      Composite endpoint of 30 day post-operative complicationsPost-operative mortality at follow up (if longer than 30 days)
      Hospital LOSComposite endpoint of total post-operative complications (if longer than 30 days)
      HRQL outcomes at follow up (EQ-5D;
      • Yates J.W.
      • Chalmer B.
      • McKegney F.P.
      Evaluation of patients with advanced cancer using the Karnofsky performance status.
      EQ-VAS;
      • Aggarwal S.
      • Qamar A.
      • Sharma V.
      • Sharma A.
      Abdominal aortic aneurysm: a comprehensive review.
      SF-36 PF; and MH subscales
      • Hughes M.J.
      • Hackney R.J.
      • Lamb P.J.
      • Wigmore S.J.
      • Christopher Deans D.A.
      • Skipworth R.J.E.
      Pre-habilitation before major abdominal surgery: a systematic review and meta-analysis.
      )
      Post-operative systemic complications for the following areas: cardiac, pulmonary, renal, neurological, delirium
      Post-operative surgical complications: haemorrhage, transfusion, limb ischaemia, limb loss, sepsis, complications requiring endovascular or open surgical re-intervention, readmission within 30 days
      ICU/HDU LOS
      Adverse outcomes that: are life threatening, result in death, cause significant morbidity, require hospitalisation or a prolonged hospital admission, require additional intervention to treat it, or lead to the participant needing to withdraw from the trial
      Discharge to independent living
      Health economic data
      LOS = length of stay; HRQL = Health related quality of life; EQ-5D = EuroQol five dimension questionnaire; EQ-VAS = EuroQol visual analogue scale; SF-36 = 36-item Short Form Survey; PF = physical function; MH = mental health; ICU = intensive care unit; HDU = high dependency unit.
      Duplicate studies were removed and the titles and abstracts were screened for potential inclusion by two independent reviewers (R.J.B. and A.D.J.). The full text reports of the remaining studies were subjected to the inclusion criteria by two independent researchers (R.J.B. and A.D.J.); any disagreements were settled by a third reviewer (S.H.R.).

      Outcomes

      The primary and secondary clinical outcomes of interest (Table 1) were based on the Society for Vascular Surgery Reporting Standards for EVAR
      • Chaikof E.L.
      • Blankensteijn J.D.
      • Harris P.L.
      • White G.H.
      • Zarins C.K.
      • Bernhard V.M.
      • et al.
      Reporting standards for endovascular aortic aneurysm repair.
      and expert opinion (Professor, D.J.S., and Consultant, T.W., Vascular Surgeons). Participant reported health related quality of life (HRQL) outcomes are also considered primary outcomes as they are important indicators of treatment success.

      Data extraction and management

      Data from the selected studies were independently extracted by one author (R.J.B.) and checked by another (S.H.R.) using a standardised pro forma; any disagreements were resolved by discussion. Authors of included papers were contacted in the event of missing data in relation to primary outcomes of interest.
      Participant baseline characteristics (mean age, proportion of females, mean AAA diameter, proportion of ethnicities) and mortality risk factors based on expert opinion (derived from European Society for Vascular Surgery guidelines
      • Wanhainen A.
      • Verzini F.
      • van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      European Society for Vascular Surgery 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      ) were extracted using a standardised data extraction tool. The Template for Intervention Description and Replication (TIDieR) checklist
      • Hoffmann T.C.
      • Glasziou P.P.
      • Boutron I.
      • Milne R.
      • Perera R.
      • Moher D.
      • et al.
      Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide.
      and an extension based on Goodwin et al.
      • Goodwin V.A.
      • Hill J.J.
      • Fullam J.A.
      • Finning K.
      • Pentecost C.
      • Richards D.A.
      Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis.
      were used to guide intervention appraisal. The interventions’ theories, designs, and procedures were extracted onto a standardised pro forma, referring to both the trial report, and any linked publications, supplementary materials and/or protocols describing intervention delivery. Event rate data were extracted for the clinical outcomes (mortality, post-operative composite complications). Means and standard deviations were extracted for the continuous outcomes (e.g. HRQL, hospital length of stay (LOS), health economic data); the standard deviation was calculated if only the standard error of the mean was provided.

      Assessment of risk of bias and overall quality of evidence

      The Cochrane Collaboration’s tool for assessing risk of bias
      • Higgins J.P.T.
      • Altman D.G.
      • Gøtzsche P.C.
      • Jüni P.
      • Moher D.
      • Oxman A.D.
      • et al.
      The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
      was applied. Each category was scored as “low”, “high”, or “unclear” risk of bias depending on the information reported. All included papers were assessed for risk of bias by two independent researchers (R.J.B. and A.D.J.) to ensure accuracy, with any disputes settled by a third reviewer (S.H.R.).

      Data synthesis and analysis

      A narrative synthesis was undertaken as the clinical and methodological heterogeneity between pre-habilitation interventions/trials precluded the pooling of data across studies. The results were grouped by pre-habilitation type and the outcomes described for each group of interventions. The results of any subgroup analyses performed, comparing outcomes between open repair and EVAR, are stated within the narrative analysis. Any adjustments made for confounding factors by the authors is specified within the results.

      Results

      Study selection and inclusion

      The PRISMA flow chart is summarised in Fig. 1. After removing duplicate titles, 1 639 papers were identified from electronic searches. Following the review of titles and abstracts, 1 586 studies were excluded, and a full text review was conducted for the remaining 53 papers. After final eligibility checks, eight studies
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      were included (901 participants; study samples ranged from 14 to 624). No further studies were identified from citation tracking or manual online searches.
      Figure 1
      Figure 1Preferred reporting items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram for literature search to identify randomised controlled trials on pre-habilitation in abdominal aortic aneurysm (AAA) repair and surgical outcomes.

      Intervention, study, and participant characteristics

      The pre-habilitation interventions all tested single component interventions including: exercise (three studies
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      ), pharmacological (three studies
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      ), and nutritional (two studies
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      ,
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      ); no study investigated the effects of a psychosocial intervention. Table 2 summarises the intervention characteristics and Table 3 further summarises the reporting of the content of the comparators and pre-habilitation interventions. Overall, both the intervention and comparator were inadequately described in each included study. Additionally, regarding materials and resources used, no study described the participant information provided. The Barry et al.
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      and Mealy et al.
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      papers reported results from the same study population and are regarded as the same cohort in analysis.
      Table 2Intervention characteristics of included randomised controlled trials comparing post-operative outcomes for patients undergoing a period of pre-habilitation prior to abdominal aortic aneurysm repair
      TrialType
      Criteria definition from TIDieR guidelines.14
      Intervention (I) and control (C)
      Criteria definition from TIDieR guidelines.14
      ,
      See Supplementary Table 1 for full details of procedures and doses reported.
      Duration
      Criteria definition from TIDieR guidelines.14
      Mode and setting
      Criteria definition from TIDieR guidelines.14
      Staff level of training
      Criteria definition from TIDieR guidelines.14
      Pilot study/Piloted
      Additional criteria definition from Goodwin et al. guidelines9 – only applicable to exercise based interventions.
      Dronkers et al. 2008
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      Exercise (unimodal)I: “Inspiratory muscle training”

      C: Usual care
      At least two weeks pre-operativeSingle centre

      1 session per week was supervised, five sessions were unsupervised

      Location of intervention provision/ administration NR
      Experienced physical therapistPilot
      Barakat et al. 2016
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      Exercise (unimodal)I: “Hospital based exercise class”

      C: Usual care
      6 weeks pre-operativeSingle centre

      Supervised

      Hospital based, physiotherapy gym
      NRPiloted
      Tew et al. 2017
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      Exercise (unimodal)I: “HIT programme”

      C: Usual care
      At least four weeks pre-operativeMulti-centre (3)

      Each session supervised

      Hospital based (no further information)
      Research nurse and physio-therapist, trained in ILSPilot
      Barry and Mealy et al. 1998
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      Pharmacological (unimodal)I: HrGH

      C: Placebo
      6 days pre-operative until six days post-operativeSingle centre

      Location of intervention provision/ administration NR
      NR_
      Decker et al. 2005
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      Pharmacological (unimodal)I: HrGH

      C: Placebo
      2 days pre-operative until 7 days post-operativeSingle centre

      Location of intervention provision/ administration NR
      NR_
      Watters et al. 2002
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      Nutrition (unimodal)I: Micronutrient supplement

      C: Placebo
      2–3 weeks pre-operative until 7 days post-operativeSingle centre

      Location of intervention provision/ administration NR
      NR_
      Garg et al. 2018
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      Nutrition (unimodal)I: Curcumin supplement

      C: Placebo
      Two days pre-operative until one day post-operativeMulticentre (10)

      Location of intervention provision/administration NR
      NR_
      HIT = high intensity interval training; HrGH = human recombinant growth hormone; ILS = immediate life support; NR = not reported.
      Criteria definition from TIDieR guidelines.
      • Hoffmann T.C.
      • Glasziou P.P.
      • Boutron I.
      • Milne R.
      • Perera R.
      • Moher D.
      • et al.
      Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide.
      See Supplementary Table 1 for full details of procedures and doses reported.
      Additional criteria definition from Goodwin et al. guidelines
      • Goodwin V.A.
      • Hill J.J.
      • Fullam J.A.
      • Finning K.
      • Pentecost C.
      • Richards D.A.
      Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis.
      – only applicable to exercise based interventions.
      Table 3Study intervention and comparator descriptions in included studies comparing post-operative outcomes for patients undergoing a period of pre-habilitation prior to abdominal aortic aneurysm repair
      TrialRationale
      Criteria definition from TIDieR guidelines.14
      Comparator
      Criteria definition from TIDieR guidelines.14
      Materials and sources
      Criteria definition from TIDieR guidelines.14
      Tailoring
      Criteria definition from TIDieR guidelines.14
      Modification
      Criteria definition from TIDieR guidelines.14
      Fidelity assessment
      Criteria definition from TIDieR guidelines.14
      Co-design
      Additional criteria definition from Goodwin et al. guidelines9 – only applicable to exercise based interventions.
      Context considered
      Additional criteria definition from Goodwin et al. guidelines9 – only applicable to exercise based interventions.
      Adherence support
      Additional criteria definition from Goodwin et al. guidelines9 – only applicable to exercise based interventions.
      Dronkers et al. 2008
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      FullPartialI: Partial

      C: Partial
      FullNRNRNRPilot studyNR
      Barakat et al. 2016
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      FullPartialI: Partial

      C: NR
      NRNRPartialNRFullPartial
      Tew et al. 2017
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      FullPartialI: Partial

      C: NR
      FullNRFullNRFeasibility studyFull
      Barry and Mealy et al. 1998
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      FullPartialI: Partial

      C: NR
      NRNRNR___
      Decker et al. 2005
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      FullPartialI: Partial

      C: NR
      NRNRNR___
      Watters et al. 2002
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      FullPartialI: Partial

      C: NR
      NRNRNR___
      Garg et al. 2018
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      FullPartialI: Partial

      C: Partial
      PartialNRNR___
      Rating system: full, describes criteria to standard of guidelines; partial, describes criteria but not to standard of guidelines; NR, not reported.
      Criteria definition from TIDieR guidelines.
      • Hoffmann T.C.
      • Glasziou P.P.
      • Boutron I.
      • Milne R.
      • Perera R.
      • Moher D.
      • et al.
      Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide.
      Additional criteria definition from Goodwin et al. guidelines
      • Goodwin V.A.
      • Hill J.J.
      • Fullam J.A.
      • Finning K.
      • Pentecost C.
      • Richards D.A.
      Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis.
      – only applicable to exercise based interventions.
      The procedures performed in each study (open or EVAR), the types of pre-habilitative interventions tested, and baseline characteristics of the patients are presented in Table 4. The studies were published in Europe
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      and North America
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      ,
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      from 1998 to 2018. The baseline characteristics and co-morbidities reported varied between studies. Similarly, duration of intervention and length of follow up were inconsistent between pre-habilitation types. Supplementary Table 2 lists the mortality risk factors and outcomes of interest reported by each study.
      Table 4General study and participant characteristics of randomised controlled trials comparing post-operative outcomes for patients undergoing a period of pre-habilitation prior to abdominal aortic aneurysm repair
      Trial (country)ProcedureType
      See Supplementary Table 1 for full details of procedures.
      Longest follow up timeAAA pathology (diameter)Participants allocated to group I/C – nAge – yFemale sex
      Females from the participants analysed (not allocated) by trials.
      White ethnicity
      Dronkers et al. 2008
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      (Netherlands)
      NRExercise2 w post-dischargeNR (NR)10/10
      Unclear if trial is reporting n of allocated or analysed participants.
      I: 70 ± 6

      C: 59 ± 6
      Groups reported by study as statistically significant (p = .001).
      I: 8 (80)

      C: 7 (70)
      NR
      Barakat et al. 2016
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      (UK)
      Open or EVARExercise3 mo post-dischargeNR (AAA ≥5.5 cm in maximum diameter,

      I: 6.0 ± 0.7

      C: 6.3 ± 0.9)
      68/68I: 73.8 ± 6.5

      C: 72.9 ± 7.9
      I: 6 (9.7)

      C: 7 (11.3)
      NR
      Tew et al. 2017
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      (UK)
      Open or EVARExercise12 w post-dischargeInfrarenal AAA (5.5 to 7 cm diameter,

      I: 6.0 ± 0.4

      C: 5.8 ± 0.4)
      27/26I: 74.6 ± 5.5

      C: 74.9 ± 6.4
      I: 2 (7.4)

      C: 1 (3.8)
      NR
      Barry and Mealy et al. 1998
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      (Ireland)
      NRPharmacological50 d post-opNR (NR)8/10
      Unclear if trial is reporting n of allocated or analysed participants.
      I: 71.1 ± 6.2

      C: 72.7 ± 4.7
      I: 2 (25)

      C: 0 (0)
      NR
      Decker et al. 2005
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      (Germany)
      OpenPharmacological7 d post-opInfrarenal AAA (NR)7/7
      Unclear if trial is reporting n of allocated or analysed participants.
      I: 67 (57–78)
      Unclear measure of dispersion reported by trial.


      C: 69.8 (51–77)
      Unclear measure of dispersion reported by trial.
      I: 2 (28.6)

      C: 3 (42.9)
      NR
      Watters et al. 2002
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      (Canada)
      NRNutrition30 d post-opInfrarenal AAA (NR)18/18
      Unclear if trial is reporting n of allocated or analysed participants.
      I: 70 ± 1

      C: 72 ± 5
      I: 14 (77.8)

      C: 14 (77.8)
      NR
      Garg et al. 2018
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      (Canada)
      Open or EVARNutrition30 d post-opNR (I: 57; 54–61

      C: 57; 55–60)
      Median and IQR reported.
      313/311I: 76 (71–80)
      Median and IQR reported.


      C: 76 (70–81)
      Median and IQR reported.
      I: 58 (19.1)

      C: 47 (15.6)
      I: 298 (98)

      C: 293 (97)
      Data are presented as n (%) or mean ± standard deviation, unless stated otherwise. I = intervention; C = control; NR, not reported; EVAR = endovascular aneurysm repair; HIT = high intensity interval training; post-op = post-operatively; COPD = chronic obstructive pulmonary disease; CPET = cardiopulmonary exercise testing; IHD = ischaemic heart disease; CVD = cerebrovascular disease; DM = diabetes mellitus; PAD = peripheral arterial disease; CHF = congestive heart failure; HTN = hypertension; HRQL = health related quality of life; LOS = length of stay; ICU = intensive care unit; HDU = high dependency
      See Supplementary Table 1 for full details of procedures.
      Females from the participants analysed (not allocated) by trials.
      Unclear if trial is reporting n of allocated or analysed participants.
      § Groups reported by study as statistically significant (p = .001).
      Median and IQR reported.
      Unclear measure of dispersion reported by trial.

      Risk of bias assessment

      The risk of bias scores for each study were variable (Fig. 2): one study
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      was deemed low risk in all domains, one study
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      had unclear risk of intention to treat (ITT) analysis methods, and six studies
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      were either at high risk in at least one domain or unclear risk in more than one domain. Specifically, five papers
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      had unclear or high risk of blinding of assessors to outcomes and five papers
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      ,
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      did not adequately describe ITT analysis methods.
      Figure 2
      Figure 2Risk of bias summary of randomised controlled trials comparing post-operative outcomes for patients undergoing a period of pre-habilitation prior to abdominal aortic aneurysm repair. + = low risk; x = high risk; – = unclear risk.

      Adherence to pre-habilitation interventions

      Four studies
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      ,
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      assessed the adherence to their interventions. Of the exercised based interventions, 32/62 (51.6%)
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      and 17/27 (63%; 95% CI 45–81)
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      attended at least 75% of classes. The two nutrition based interventions reported pill counts to assess adherence, reporting at least 90% compliance in one study
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      and a median of 32/32 pills consumed in the other.
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      Neither of the pharmacological based studies
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      measured compliance.

      Exercise based interventions

      Primary outcomes

      Two studies
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      ,
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported post-operative 30 day mortality and neither found significant differences between groups. Barakat et al.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      reported a significant reduction in the median hospital LOS in the exercise group (7.0 days, interquartile range [IQR] 5.0, 9.0) compared with usual care (8.0 days, IQR 6.0, 12.3) (p = .025). Subgroup analysis revealed significant reduction in hospital LOS following EVAR only, not open repair. Tew et al.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      found the median hospital LOS to be 7 days (IQR 4.5, 8.5) in the intervention group compared with six days (IQR 4, 8) in the control. Two studies
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      ,
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported HRQL between the exercise and usual care groups at three months after discharge. Tew et al.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported significant improvements in the EuroQol five dimension questionnaire (EQ-5D) (95% CI, 0.005 – 0.148) and 36 item Short Form Survey (SF-36) physical function (PF) subscale (95% CI, 0.4 to 5.4) following pre-operative exercise, but no difference in the EuroQol visual analogue scale (EQ-VAS) and SF-36 mental health (MH) subscale (analysis adjusted for baseline scores). In contrast, Barakat et al.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      reported no differences in mobility impairment using an undefined measure. Dronkers et al.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      circulated a patient satisfaction questionnaire to the intervention group only.
      No exercise based study reported the composite endpoint of 30 day post-operative complications.

      Secondary outcomes

      Two studies
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      ,
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported the composite endpoint of total post-operative complications. Barakat et al.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      found significant reductions in combined cardiac, pulmonary, and renal complications at three months after discharge with exercise (14/62, 22.6%) compared with usual care (26/62, 41.9%) (p = .021). When the authors individually analysed systemic complications, cardiac and renal complications were significantly reduced but pulmonary were not. Additionally, subgroup analysis within the exercise group showed that cardiac and renal complications were significantly reduced following open repair only, not EVAR. Tew et al.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported Post-Operative Morbidity Survey scores and did not find significant differences between intervention and control until discharge date. Dronkers et al.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      did not find a significant reduction in the incidence of atelectasis – the follow up period was not defined. Barakat et al.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      also reported rates of re-operation and post-operative bleeding or transfusion of more than four units but found no significant differences between groups. No other rates of surgical complications were described in the three studies.
      Tew et al.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported three adverse events (two withdrawals and referral to cardiology, one cessation of exercise with angina) in the exercise group but no comparison was made with usual care. The other two studies
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      ,
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported “no adverse events” but did not define what constituted an adverse event.
      No exercise based study compared total post-operative mortality at follow up or the rates of discharge to independent living between groups. Dronkers et al.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      reported the death of one participant in the intervention group but did not report whether deaths occurred in the control group.

      Pharmacological based interventions

      Primary outcomes

      Barry and Mealy and colleagues
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      reported one post-operative death (in the control group) within 30 days and a mean hospital LOS of 13 days (standard error of the mean [SEM] 2) in the intervention group compared with 17 (SEM 3) in the control. Decker et al.
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      found no significant difference in mean hospital LOS between the human recombinant growth hormone (HrGH) and placebo groups.
      No pharmacological based study reported composite endpoint of 30 day post-operative complications or HRQL outcomes at follow up.

      Secondary outcomes

      Barry and Mealy and colleagues
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      reported post-operative mortality and systemic complications at 50 days following surgery: one patient in the control group suffered a brain stem infarct which subsequently led to respiratory failure and death. Decker et al.
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      stated “no complications occurred” but did not define their criteria. Neither study reported significant differences in intensive care unit (ICU)/high dependency unit (HDU) LOS. Barry and Mealy and colleagues
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      reported adverse events and described one patient who experienced hyperglycaemia requiring treatment due to the HrGH therapy.
      No pharmacological based study reported rates of post-operative surgical complications or discharge to independent living.

      Nutrition based interventions

      Primary outcomes

      Both studies
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      ,
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      reported post-operative 30 day mortality and median
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      or mean
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      hospital LOS, no significant differences were found. Garg et al.
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      found no significant reduction in the composite endpoint of 30 day post-operative complications (including 14 clinical events) following curcumin supplementation. Watters et al.
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      examined HRQL outcomes and found significant improvements in the physical function (p < .05) and general health (p < .05) components of SF-36 in the micronutrient supplementation group at four weeks following surgery. No significant differences were reported in the EQ-VAS at seven days, Karnofsky performance status
      • Yates J.W.
      • Chalmer B.
      • McKegney F.P.
      Evaluation of patients with advanced cancer using the Karnofsky performance status.
      at four weeks, or other SF-36 components at four weeks following surgery.

      Secondary outcomes

      Garg et al.
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      reported total post-operative mortality (at 90 days after surgery) and found no significant difference. The same paper also compared the rate of acute kidney injury (AKI) in the first 48 post-operative hours and reported a significant decrease with curcumin supplementation (51/301, 16.9%) vs. placebo (30/302, 9.9%) (p = .010). Watters et al.
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      measured ICU/HDU LOS and found no significant differences between groups. Garg et al.
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      reported no significant differences in rates of clinically important bleeding or adverse events between groups.
      No nutrition based study reported the composite endpoint of total post-operative complications or rates of discharge to independent living.
      No differences in outcome between open and EVAR procedures were reported by Garg et al following subgroup analysis.

      Health economic data analysis

      One study
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      performed an economic evaluation of their pre-habilitation intervention against the comparator. Tew et al.,
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      who conducted a feasibility study, found no significant comparison in the bootstrapped mean differences of the total costs between their exercise therapy and usual care.

      Discussion

      Main findings

      Research into the effectiveness of pre-habilitation between diagnosis and elective surgery is increasing. Whilst commonly regarded as exercise based, there are other strategies to optimise a patient’s physical and mental health. This review summarised the content of pre-habilitation interventions and explored their effect on post-operative outcomes for patients undergoing AAA repair. Seven trials
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      • Watters J.M.
      • Vallerand A.
      • Kirkpatrick S.M.
      • Abbott H.E.
      • Norris S.
      • Wells G.
      • et al.
      Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy.
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      were identified evaluating single component pre-habilitation interventions testing the effectiveness of exercise (n = 3), pharmacological interventions (HrGH therapy; n = 2), or nutritional supplementation (n = 2, micronutrient, curcumin); no trials tested interventions targeting psychosocial factors; only one included assessment of the health economic impact.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      When assessed relative to standardised reporting guidelines,
      • Goodwin V.A.
      • Hill J.J.
      • Fullam J.A.
      • Finning K.
      • Pentecost C.
      • Richards D.A.
      Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis.
      ,
      • Hoffmann T.C.
      • Glasziou P.P.
      • Boutron I.
      • Milne R.
      • Perera R.
      • Moher D.
      • et al.
      Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide.
      while all studies reported the rationale of their intervention, none satisfied all the criteria regarding the content of intervention and/or comparator groups.
      Over half the trials were of unknown or high risk of bias, and the clinical and methodological heterogeneity observed ruled out meta-analysis. The outcomes reported varied considerably, in part reflecting the different interventions evaluated. Notwithstanding this, the measures likely to be of importance to patients (e.g., HRQL and functioning) were reported sparsely. Important subgroup analysis and adjustments for confounding factors were also limited. Regarding the three exercise based trials, it should be noted only one
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      was sufficiently powered to identify clinically important differences; the other two were pilot
      • Dronkers J.
      • Veldman A.
      • Hoberg E.
      • van der Waal C.
      • van Meeteren N.
      Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study.
      or feasibility
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      trials.
      Overall, hospital LOS was significantly improved in one study
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      and HRQL outcomes in another
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      following different pre-operative exercise regimens. One study
      • Garg A.X.
      • Devereaux P.J.
      • Hill A.
      • Sood M.
      • Aggarwal B.
      • Dubois L.
      • et al.
      Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.
      reported reduced rates of AKI following curcumin supplementation. There was no evidence of differences in clinical outcomes in the pharmacological based studies.
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Decker D.
      • Springer W.
      • Tolba R.
      • Lauschke H.
      • Hirner A.
      • von Ruecker A.
      Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.

      Findings in context

      A recent meta-analysis
      • Hughes M.J.
      • Hackney R.J.
      • Lamb P.J.
      • Wigmore S.J.
      • Christopher Deans D.A.
      • Skipworth R.J.E.
      Pre-habilitation before major abdominal surgery: a systematic review and meta-analysis.
      investigating the effects of exercise therapies prior to abdominal operations (cancer resection, AAA repair, bariatric surgery) observed a reduction in overall morbidity (n = 9 trials; odds ratio [OR] 0.63, 95% CI 0.46 – 0.87) and pulmonary morbidity (n = 9 trials; OR 0.40, 95% CI 0.23 – 0.68) following exercise intervention compared with controls. However, the review demonstrated that there was insufficient evidence to make recommendations regarding the most effective types of exercise when limiting to people undergoing AAA repair. Furthermore, pre-habilitation may provide varied benefit depending on surgical approach (EVAR or open) as shown by the differences seen in the exercise study by Barakat et al.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      Although a small trial
      • Barry M.C.
      • Mealy K.
      • Sheehan S.J.
      • Burke P.E.
      • Cunningham A.J.
      • Leahy A.
      • et al.
      The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.
      ,
      • Mealy K.
      • Barry M.
      • O’Mahony L.
      • Sheehan S.
      • Burke P.
      • McCormack C.
      • et al.
      Effects of human recombinant growth hormone [rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.
      investigated the effects of HrGH on cardiorespiratory function and the acute inflammatory response; more than 20 years later HrGH is not widely used for pre- or post-surgical optimisation. As ischaemic heart disease, congestive heart failure, diabetes mellitus, renal insufficiency, peripheral arterial disease, and chronic obstructive pulmonary disease are recognised predictors of post-operative complications,
      • Wanhainen A.
      • Verzini F.
      • van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      European Society for Vascular Surgery 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      all remain plausible targets for pre-operative optimisation. European guidelines
      • Wanhainen A.
      • Verzini F.
      • van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      European Society for Vascular Surgery 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      recommend blood pressure control, statins, and antiplatelet therapy for all patients with AAA, but no drug has been found to slow the rate of AAA growth.
      Interestingly, smoking is the strongest associated modifiable risk factor of AAA.
      • Aggarwal S.
      • Qamar A.
      • Sharma V.
      • Sharma A.
      Abdominal aortic aneurysm: a comprehensive review.
      There is evidence that psychological intervention with behavioural support have been shown to improve the rates of smoking cessation and reduce anxiety levels in patients awaiting surgery.
      • Thomsen T.
      • Villebro N.
      • Møller A.M.
      Interventions for preoperative smoking cessation.
      ,
      • Alanazi A.A.
      Reducing anxiety in preoperative patients: a systematic review.
      Most AAA guidelines

      Overview. Abdominal aortic aneurysm: diagnosis and management. Guidance. NICE. Available at: https://www.nice.org.uk/guidance/ng156 [Accessed 7 March 2020].

      ,
      • Wanhainen A.
      • Verzini F.
      • van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      European Society for Vascular Surgery 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      ,
      • Chaikof E.L.
      • Dalman R.L.
      • Eskandari M.K.
      • Jackson B.M.
      • Lee W.A.
      • Mansour M.A.
      • et al.
      The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.
      recommend smoking cessation, often at least two weeks before surgery, however the value of incorporating this support into pre-habilitation for patients with AAA is untested.
      Pre-operative nutrition is recommended increasingly for surgical management. Malnutrition results in poor patient outcomes due to the high metabolic demands of the surgical stress response.
      • Gillis C.
      • Wischmeyer P.E.
      Pre-operative nutrition and the elective surgical patient: why, how and what?.
      An observational study
      • Inagaki E.
      • Farber A.
      • Eslami M.H.
      • Kalish J.
      • Rybin D.v.
      • Doros G.
      • et al.
      Preoperative hypoalbuminemia is associated with poor clinical outcomes after open and endovascular abdominal aortic aneurysm repair.
      of 15 002 patients reported significantly increased 30 day mortality, re-operation rates, and pulmonary complications in patients undergoing AAA repair with hypoalbuminaemia (a marker of malnutrition). While recent guidelines
      • Wanhainen A.
      • Verzini F.
      • van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      European Society for Vascular Surgery 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      ,
      • Chaikof E.L.
      • Dalman R.L.
      • Eskandari M.K.
      • Jackson B.M.
      • Lee W.A.
      • Mansour M.A.
      • et al.
      The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.
      advise the assessment and optimisation of nutritional status in the pre-operative period, it is unclear whether it is changing clinical practice, or could be included effectively as part of pre-habilitation.
      Studies seeking to combine different treatments into a multimodal pre-habilitation package are limited. Bolshinsky et al.
      • Bolshinsky V.
      • Li M.H.G.
      • Ismail H.
      • Burbury K.
      • Riedel B.
      • Heriot A.
      Multimodal pre-habilitation programs as a bundle of care in gastrointestinal cancer surgery: a systematic review.
      systematically reviewed RCTs and observational evidence to investigate the effect of multi-modal pre-habilitation in gastro-intestinal cancer surgery. Like this review, they were unable to draw conclusions about its effectiveness and its integration into normal care due to lack of studies. An RCT
      • Barberan-Garcia A.
      • Ubré M.
      • Roca J.
      • Lacy A.M.
      • Burgos F.
      • Risco R.
      • et al.
      Personalised pre-habilitation in high-risk patients undergoing elective major abdominal surgery: a randomized blinded controlled trial.
      comparing multimodal pre-habilitation (personalised programmes to promote healthy living, exercise, and motivational interviewing) in patients undergoing major abdominal surgery showed reduced post-operative complications compared with standard care. While there remains considerable potential to undertake sufficiently powered pre-habilitation trials in AAA repair, evaluating both single and multimodal interventions, the lack of evidence means it is too early to make evidence based recommendations for clinical practice.

      Study strengths and limitations

      Despite adopting a broad definition of pre-habilitation, only seven trials were deemed eligible for inclusion. By applying standardised checklists,
      • Goodwin V.A.
      • Hill J.J.
      • Fullam J.A.
      • Finning K.
      • Pentecost C.
      • Richards D.A.
      Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis.
      ,
      • Hoffmann T.C.
      • Glasziou P.P.
      • Boutron I.
      • Milne R.
      • Perera R.
      • Moher D.
      • et al.
      Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide.
      the contents of interventions were described systematically and important gaps in the reporting of treatment protocols were identified. However, the small number of studies, combined with poor reporting of pre-operative risk factors and heterogeneity of intervention components, limited the ability to evaluate the effect of pre-habilitation on AAA repair. Importantly, two studies
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      ,
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      testing exercise regimens reported low intervention adherence (51% and 63%) and this has the potential to dilute treatment effects in an ITT analysis. It remains possible that treatment effects could be improved by incorporating strategies to increase adherence to exercise interventions, but this is currently untested. Furthermore, all interventions were unimodal thus any potential synergistic effects of combining treatments were not measurable.

      Implications for practice

      Whilst a pre-habilitation care bundle could provide an answer to the poor fitness levels in pre-operative AAA patients, it is important to consider the challenges of implementing it in practice. An editorial,
      • Giles C.
      • Cummins S.
      Pre-habilitation before cancer treatment.
      responding to the new Macmillan Cancer Support pre-habilitation guidance, raises concerns about the potential burden on patients. Pre-habilitation aims to empower the patient by giving them control, but this new responsibility, amongst the high volume of information that is delivered alongside, could be overwhelming. This further supports the inclusion of psychological interventions in pre-habilitation, as well as adherence support strategies to enhance patient compliance.
      • Hoffmann T.C.
      • Glasziou P.P.
      • Boutron I.
      • Milne R.
      • Perera R.
      • Moher D.
      • et al.
      Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide.
      The optimum timeframe to deliver pre-habilitation care also needs further investigation. The trial by Barakat et al.
      • Barakat H.M.
      • Shahin Y.
      • Khan J.A.
      • McCollum P.T.
      • Chetter I.C.
      Preoperative supervised exercise improves outcomes after elective abdominal aortic aneurysm repair: a randomized controlled trial.
      showed improved post-operative outcomes with their six week exercise programme whilst current UK guidance advises AAA repair to occur within 8 weeks of diagnosis. Therefore, there is an evident window of time which should be used productively to improve the pre-operative fitness of patients with AAA. Clearly, the perceived benefit of any pre-habilitative intervention would need to be weighed against the individual’s risk of rupture by delaying the definitive repair. Several weeks of exercise based pre-habilitation may not be appropriate in those with very large aneurysms, who tend to be admitted and repaired on an urgent basis. Cardiopulmonary testing is already being used to assess patients’ pre-operative fitness and it could provide an opportunity to recognise individual needs prior to the invasive procedure.
      • Kato M.
      • Kubo A.
      • Green F.N.
      • Takagi H.
      Meta-analysis of randomized controlled trials on safety and efficacy of exercise training in patients with abdominal aortic aneurysm.
      ,
      • Wanhainen A.
      • Verzini F.
      • van Herzeele I.
      • Allaire E.
      • Bown M.
      • Cohnert T.
      • et al.
      European Society for Vascular Surgery 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
      ,
      • Carlisle J.B.
      • Danjoux G.
      • Kerr K.
      • Snowden C.
      • Swart M.
      Validation of long-term survival prediction for scheduled abdominal aortic aneurysm repair with an independent calculator using only pre-operative variables.
      Moreover, Tew et al.
      • Tew G.A.
      • Batterham A.M.
      • Colling K.
      • Gray J.
      • Kerr K.
      • Kothmann E.
      • et al.
      Randomized feasibility trial of high-intensity interval training before elective abdominal aortic aneurysm repair.
      reported no operations were delayed due to their exercise programme. It is also possible that initiating pre-habilitative modalities at different times, even before the patient has reached the threshold for surgery, results in beneficial effects. Twelve studies were excluded as the interventions were only administered in the peri-operative period (Fig. 1) and there might be some value to these as part of an expanded multimodal programme.

      Implications for research

      There is a paucity of high quality research into the acceptability, and clinical and cost effectiveness of different types of pre-habilitation intervention, and on how to combine them to achieve the best outcomes for patients waiting for AAA repair. The use of reporting standards (e.g., TIDIER checklist
      • Hoffmann T.C.
      • Glasziou P.P.
      • Boutron I.
      • Milne R.
      • Perera R.
      • Moher D.
      • et al.
      Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide.
      including the Goodwin et al.
      • Goodwin V.A.
      • Hill J.J.
      • Fullam J.A.
      • Finning K.
      • Pentecost C.
      • Richards D.A.
      Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis.
      extension for physical interventions), can guide the design of future pre-habilitation interventions thus improving study quality and generalisability. Authors should carefully consider the issues surrounding compliance to pre-habilitative interventions during the design phase to better establish its feasibility and effect. There is an urgent need to agree a core outcome measurement set for such trials, including outcomes of importance to both clinicians and patients, to allow direct comparisons between studies and to aid meta-analysis in the future. Together with consistent reporting of important baseline characteristics, such as AAA diameter and the presence of co-morbidities, adherence rates, and the procedures performed (with subgroup analysis), care providers will be more informed to decide which populations should receive certain treatments.

      Conclusions

      The time between diagnosis and repair of an AAA presents an opportunity to implement pre-habilitative interventions and optimise pre-operative state to improve post-operative outcomes. RCTs investigating pre-habilitation in patients undergoing AAA repair are limited in availability and quality, limiting the ability to draw robust conclusions to inform practice. More high quality trials investigating and comparing the various pre-habilitative modalities are required to inform the clinical and cost effectiveness, and to guide best practice for patients undergoing AAA repair.

      Conflict of interest

      No authors of this study have any conflicting interests.

      Funding

      This study was not funded.

      Acknowledgements

      The authors would like to thank Professor R. Foy and Professor R. Neal for their guidance during the study design phase.

      Appendix A. Supplementary data

      The following is the Supplementary data to this article:

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      Linked Article

      • Preparing for Success
        European Journal of Vascular and Endovascular SurgeryVol. 61Issue 5
        • Preview
          Abdominal aortic aneurysm (AAA) repair is a significant stressor for vascular patients who often already have multiple comorbidities. The importance of comprehensively preparing patients for AAA repair is becoming recognised increasingly. The review by Bonner et al. effectively summarises the current literature on the types of prehabilitative interventions offered and the impact on peri-operative outcomes.1 There are some key considerations for successful real world implementation that warrant further discussion.
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