Optimization of Surgical Outcomes with Prehabilitation

Appl. Physiol. Nutr. Metab. Downloaded from www.nrcresearchpress.com by MCGILL UNIVERSITY on 06/02/15 For personal use only. This Just-IN manuscript is the accepted manuscript prior to copy editing and page composition. It may differ from the final official version of record.

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Prehabilitation

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Optimization of Surgical Outcomes with Prehabilitation

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Daniel Santa Mina, PhD, RKin1,2, Celena Scheede-Bergdahl, PhD3.4, Chelsia Gillis, MSc, RD3 and Francesco Carli MD, MPhil3

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ELLICSR, Princess Margaret Cancer Centre, Toronto, Ontario

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Kinesiology Program, University of Guelph-Humber, Toronto, Ontario

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Department of Kinesiology and Physical Education, McGill University, Montreal, Québec

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Department of Anesthesia, McGill University, Montreal, Québec

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CSB: McGill University, Department of Kinesiology and Physical Education, 475 Pine Avenue West, Montreal, Quebec H2W 1S4 [email protected], t. 514-398-4184 x00839

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FC: McGill University Health Centre, 1650 Cedar Ave., Montreal, Quebec, Canada, H3G 1A4; Rm D10.14; [email protected]; t. 514-934-1934 x43261; f. 514-934-8249

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CG: McGill University Health Centre, 1650 Cedar Ave., Montreal, Quebec, Canada, H3G 1A4; Rm D10.14; [email protected]; t. 514-934-1934 x43261; f. 514-934-8249

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Submitted to: Applied Physiology, Nutrition, and Metabolism Daniel Santa Mina, PhD – Corresponding Author ELLICSR, The Princess Margaret Cancer Centre 585 University Avenue, Munk Building, BCS021 Toronto, ON, Canada M5G 2C4 t. (1) 416-581-7784 e. [email protected]

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Running Head: Prehabilitation

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Number of Words: (Max 2000) – 1749 (without references). Number of Tables: 0 Number of Figures: 1 (equivalent to 250 words)

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Abstract

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The concept of preparing surgical candidates with various modalities designed to increase

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physical, physiological, metabolic and psychosocial reserves, is known as prehabilitation.

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Prehabilitation has garnered significant attention in recent years as evidence grows describing

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benefits to clinical and quality of life outcomes. Recent research examining hospital length of

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stay and readmission rates provides promising findings with respect to the value of

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prehabilitation in economic and sustainable healthcare models. The role of prehabilitation across

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the surgical experience exploits common surgical wait-times and the teachable moment that

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many patients experience upon the identification of a surgical requirement in order to improve

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the pre, peri, and postoperative experience. Prehabilitation incorporates numerous systemic and

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regional approaches to conditioning the surgical candidate. These include exercise, nutrition,

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education, and/or psychosocial approaches that are intended to improve preoperative fitness and

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preparedness. Importantly, this also promotes and facilitates health behaviour changes not only

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preoperatively but during the postoperative period and over the long-term. In this paper, we

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briefly review the historical and current perspectives on prehabilitation and comment on

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opportunities for greater clinical and empirical understanding in this field.

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[Word Count = 181]

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Keywords: Prehabilitation, Rehabilitation, Surgery, Exercise, Post-operative Recovery

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Prehabilitation

Introduction:

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Surgery is indicated to cure or palliate numerous physical ailments; however, it represents

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a major stress that often leads to adverse effects unrelated to treatment objectives. These adverse

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effects have profound negative impacts on the capacity to perform activities of daily living,

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subsequently impairing quality of life (Litwin et al. 1999; Phillips-Bute et al. 2006). For example,

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Litwin et al. (Litwin et al. 1999) found that 3 months postoperatively, only 30% and 36% of

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patients had returned to baseline values of general physical function and energy levels,

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respectively, in men undergoing radical prostatectomy for prostate cancer. Similarly, patients

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undergoing major surgery experience disturbed sleep, decreased capacity to concentrate and

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physical fatigue for up to 9 weeks after discharge (Salmon and Hall 1997). Investigations into

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modifiable risk factors have identified preoperative physical fitness, physical activity, and

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nutritional status as predictors of surgical complications and recovery (Carswell et al. 1978;

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Cook et al. 2001; Braga et al. 2013; Gillis et al. 2014; Santa Mina et al. 2014b). Conversely,

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preoperative deterioration of fitness has been associated with more surgical complications and

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requirements for intensive care that may be exacerbated by the deleterious effects of prolonged

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postsurgical bed rest and poor nutritional intake (Mayo et al. 2011; Kortebein et al. 2008;

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Ferrando et al. 2010; Kassin et al. 2012). These findings have precipitated strategies to buffer

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against the expected decline in physical function and overall wellbeing associated with surgery.

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To improve postsurgical recovery, an important question revolves around when the most

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opportune time is to introduce recovery-optimizing behaviours. The postsurgical period may not

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be ideal for the introduction of new, positive health behaviours due to concerns related to

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perturbing the healing process. Rather, the preoperative period may be a more physically and

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Prehabilitation

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emotionally salient time to intervene with patients by capitalizing on: i) better physical condition

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of the patient (compared to the acute postoperative period); ii) opportunity to effectively use

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surgical wait-times; and iii) a ‘teachable moment’ for the patient that accompanies reflection

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upon the need for major surgery. Ostensibly, the preoperative period may be an optimal time to

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invest into modifiable risk factors, such as exercise and diet, which protect physiologic reserves

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in the face of surgical insult. Indeed, clinicians and researchers are now examining preoperative

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lifestyle interventions aimed at improving the surgical experience and clinically relevant

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outcomes. This strategy is commonly referred to as pre-habilitation.

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Prehabilitation is defined as the process of enhancing one’s functional and mental

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capacity to buffer against potential deleterious effects of a significant stressor (Carli et al. 2005).

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In a surgical setting, preoperative physical (e.g. exercise and diet) and/or psychological

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conditioning (e.g. stress management and education) aims to increase body and mind reserves to

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prevent the anticipated surgery-related declines in function and wellbeing (Figure 1) (Carli and

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Zavorsky 2005). Definitions of prehabilitation have evolved to incorporate a clinical outcome or

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impairment-prevention/mitigation approach that may be applied to specific morbidities, such as

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“a process on the cancer continuum of care that occurs between the time of cancer diagnosis and

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the beginning of acute treatment and includes physical and psychological assessments that

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establish a baseline functional level, identify impairments, and provide interventions that

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promote physical and psychological health to reduce the incidence and/or severity of future

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impairments” (Silver et al. 2013).

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baseline function, anticipated surgery-related dysfunction, and comprehensive and individualized

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program towards optimal recovery. It is also worth distinguishing prehabilitation from Enhanced

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Recovery After Surgery (ERAS) programs that employ intra- and postoperative surgical care

This latter definition requires a detailed understanding

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Prehabilitation

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plans intended on accelerating recovery. As such, ERAS may incorporate prehabilitation but

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itself represents a more comprehensive surgical recovery approach.

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‘Physical activity’ refers to movement that incurs a metabolic cost above rest, while

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‘exercise’ further specifies physical activity to be done routinely with intent to improve health.

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‘Exercise’ can adopt different meanings across contexts and may be further qualified for the

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clinical setting. For example, therapeutic exercise can refer to clinically supervised and/or

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prescribed exercises that are targeted at resolving specific morbidities. Depending on the

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jurisdiction and local healthcare system, therapeutic exercises may be covered by public insurers.

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Within the context of prehabilitation, interventions have commonly employed systemic (general)

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exercise and/or tissue-specific (therapeutic) exercise, depending on the disease and treatment-

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related sequelae. The former approach addresses the expected musculoskeletal/cardiovascular

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deconditioning that occurs following prolonged periods of sedentary behaviour (i.e., relative

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immobilization before and after surgery). The latter approach is beneficial for localized

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morbidity, and would include exercises such as deep breathing and diaphragmatic exercises for

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thoracic surgery patients, or knee flexion/extension exercises for knee replacement surgery

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patients. Systematic reviews of both approaches are hampered by heterogeneity in study

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population and prehabilitation strategies and overall paucity of high quality methodologies that

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contribute to limitations in interpretation. While the evidence of benefit in some specific fields

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remains equivocal, others have shown promise. For example, a systematic review of preoperative

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physiotherapy in arthroplastic surgery indicated no benefit for knee patients and inconclusive

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evidence for hip patients (Ackerman and Bennell 2004). Some authors suggest that chronic joint

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disease is resistant to a brief preoperative physiotherapy intervention; or alternatively, that joint

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replacement surgery provides such marked improvements in symptoms that it overshadows the 5

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Prehabilitation

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relatively smaller gains related to preoperative exercise (D'Lima et al. 1996; Gocen et al. 2004).

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Evidence for cardiac, pulmonary and major abdominal surgery; however, indicates that

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preoperative diaphragmatic and respiratory muscle training, including incentive spirometry and

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coughing exercises can improve numerous postoperative outcomes (Fagevik Olsen et al. 1997;

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Moy et al. 1999; Hulzebos et al. 2006). We recently reviewed the literature examining the effect

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of total-body (aerobic and/or resistance training) prehabilitation and found that prehabilitation

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consistently improved physical function during the preoperative period with studies reporting a

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worsening of physical and psychosocial symptoms in non-exercising control subjects (Santa

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Mina et al. 2014a).

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hospitalization, and an accelerated return to baseline physical function compared to controls.

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Unfortunately, few interventions employed a comprehensive prehabilitation approach (including

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diet, education, or psychotherapy) to address the decline in global wellbeing that persists

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postoperatively.

Postoperatively, prehabilitated participants had reduced pain and

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Prehabilitation research now extends beyond exercise approaches and examines the

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synergistic effect of preoperative dietary interventions (e.g. Carli et al. 2010, Carli and Scheede-

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Bergdahl 2015). Severe undernutrition is an independent risk factor for surgical complications,

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mortality, length of hospitalization, and costs (Weimann et al. 2006; Braga et al. 2009).

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Consequently, nutritional support, including oral nutrition supplementation (ONS), is

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recommended prior to surgery for those with and at risk of undernutrition (Weimann et al. 2006;

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Braga et al. 2009; McClave et al. 2013). In fact, preoperative nutritional support for 1-2 weeks

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may be indicated in severe cases even if surgery has to be delayed (Weimann et al. 2006; Braga,

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Ljungqvist et al. 2009). Beyond therapeutic responses to at-risk and undernourished patients,

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there appears to be an independent benefit of preoperative ONS to ensure dietary protein 6


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requirements are met prior to surgery. This proactive strategy manages nutritional status

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throughout the perioperative period, rather than correcting deficiencies later (McClave et al.

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2013). Additionally, preoperative ONS with immunomodulating nutrients has been found to

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decrease infectious complications and length of hospital stay in traditional care settings (Braga et

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al. 2013). The benefit to outcomes such as fatigue, wound healing, and functional capacity may

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be due to satisfying an increased demand for protein via a stress response that can result in

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protein depletion and muscle atrophy (Weissman 1990; Watters et al. 1993). To further examine

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the role of ONS-based prehabilitation, we are currently conducting a double-blind RCT to

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compare nutrition counselling with a placebo versus nutrition counselling with whey protein

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supplementation initiated four weeks before surgery (clinical trial registration #: NCT

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01727570).

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As nutritional supplementation and exercise have independently demonstrated benefit for

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surgical patients, it is essential to evaluate their synergistic roles as the availability of substrates

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becomes more crucial for exercise-based interventions in the perioperative setting. Therefore, a

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multimodal approach to prehabilitation that comprises tailored exercises and nutritional

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supplementation is likely the most effective approach to improving the rate and quality of

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surgical recovery. To examine this, we assessed a 1-month trimodal prehabilitation program in

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42 patients undergoing colorectal cancer surgery compared to 45 controls (Li et al. 2012). The

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trimodal prehabilitation program comprised of aerobic exercise 3x/week, nutritional counselling

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for the reduction of dietary risk factors (e.g. body fat) and whey protein supplementation to meet

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a total dietary intake of 1.2g/kg-body weight/day, and a 90-minute anxiety-reduction and stress

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management session with a clinical psychologist. While the complication rates and the hospital

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length of stay were similar between groups, prehabilitation patients experienced significantly 7

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greater 6-minute walk test performance at both 1-month (51.5m) and 2-months (84.5m) after

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surgery compared to controls. The prehabilitation group also reported greater postoperative

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physical activity throughout the entire follow-up period. Importantly, 2 months following

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surgery, 81% of prehabilitation patients recovered to baseline walking capacity compared with

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40% of the control group.

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As the prevalence of bariatric surgery has risen dramatically in Canada and the US over

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recent years (Buchwald and Oien 2009), this group represents a key opportunity to evaluate the

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effect of prehabilitation.

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surgery, improved candidacy, as well as enhanced peri- and postoperative outcomes may be

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achieved with preoperative weight loss through lifestyle approaches. In fact, some surgeons and

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insurance companies mandate attempts at preoperative weight loss prior to bariatric surgery

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(Livhits et al. 2009). A review by Livhits et al (2009) indicated that patients could reduce

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preoperative body weight by 10% without significant increase to perioperative risk. Moreover,

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among the higher quality studies included in the review, patients who achieved preoperative

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weight loss achieved greater postoperative weight loss.

Despite the relatively low mortality rate associated with bariatric

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Historically, postoperative recovery has been expedited and improved with structured

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rehabilitation programs after most major surgeries (Ades 2001; Kuster 2002; Nici et al. 2006).

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Relatively little is understood about the differential benefits of prehabilitation compared to

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rehabilitation in a surgical setting; however, to our knowledge, our group is the first to address

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this gap in the literature (Gillis et al. 2014). We randomized 38 and 39 patients undergoing

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colorectal resection for cancer to either prehabilitation or rehabilitation, respectively. Each group

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underwent a 1-month intervention comprising home-based, moderate-intensity aerobic and

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resistance training, nutritional counselling with whey protein supplementation, and relaxation

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exercises, differing only by time of implementation; whereas the prehabilitation group started 1-

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month before surgery and the rehabilitation group started immediately following surgery. We

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observed an increase in approximately 25m in preoperative walking capacity in the

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prehabilitation group that offset the average 22m decline in walking capacity that occurred over

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the 1 month following surgery. Two months postoperatively, prehabilitated participants had

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significantly greater walking capacity and more frequently recovered to baseline walking capacity

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than the rehabilitation group. While both groups had comparable complication rates, lengths of

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stay, and other clinical measures, the value of improved functional capacity observed in the

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prehabilitation group is relevant for the reduction in cardiorespiratory complications has been

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previously reported (Lee et al. 2013). Further comparisons of prehabilitation and rehabilitation

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are warranted.

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Take Home Points

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• Prehabilitation research continues to expand to identify new surgical and non-surgical

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populations, as well as the incorporation of additional or novel strategies to optimize

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peri- and post-treatment health.

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• Current prehabilitation approaches are positioned along a continuum of intensities and

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services, ranging from generalized, educational materials to personalized, multi-modal,

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lifestyle and morbidity-targeted interventions delivered by clinicians.

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• Irrespective of the approach, critical to the concept prehabilitation and consistent with the

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empirical literature is an investment in the preoperative setting with programmatic

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content that prepares the patient physically, psychologically, and/or emotionally for the 9

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pending treatment.

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• Clinicians and researchers alike are further challenged to disentangle the relative

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contributions of the individual elements of prehabilitation interventions as well as their

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parameters, such as intervention timing, exercise intensity and modalities, and nutritional

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supplementation composition and quantity.

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• With the intentions of facilitating a more rapid rate of recovery, limiting postoperative

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discomfort and dependence, and reducing healthcare resources, prehabilitation will likely

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have significant positive patient-health and healthcare cost implications.

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ACKNOWLEDGMENTS

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CONFLICT OF INTEREST

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None declared.

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Prehabilitation

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Figure Captions

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Figure 1. Conceptual model of generalized functional ability trajectory in patients undergoing

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prehabilitation compared to individuals prescribed rehabilitation only.

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Functional Capacity

Appl. Physiol. Nutr. Metab. Downloaded from www.nrcresearchpress.com by MCGILL UNIVERSITY on 06/02/15 ly. This Just-IN manuscript is the accepted manuscript prior to copy editing and page composition. It may differ from the final official Page 17 of 17

Functional Threshold

Pre-op Acute Post-op

Legend Prehabilitation Non-Prehabilitation Rehabilitation Post-Rehab