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7 Patient Optimisation for Colorectal Surgery 183
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may include smoking cessation (with the aim of reducing pulmonary complications and surgical site infection). Addressing the patient’s nutritional status is
also important (through protein-rich supplementary drinks, or encouraging weight
loss in patients with a high body mass index (BMI)) [32], and undernourished
patients are twice as likely to be readmitted within 30 days after elective colorectal surgery [32], and conversely, obese patients are 12 times more likely to
experience post-operative complications (including pulmonary complications and
surgical site infections) [62]. Furthermore, pre-assessment may allow identification
of other potential pharmacological or medical problems which may be affected by
surgery. An assessment of the physical activity status of patients may also impact
post-operative outcomes following abdominal surgery [25], with physical activity significantly improving short-term mortality rates, length of hospital stay and
discharge destination from hospital [25].
Assessment in the pre-operative setting is typically on an outpatient basis,
including a medical assessment for fitness for surgery and a nursing assessment of
what the ERAS program entails, and clarification of patient expectations following
surgery (such as estimated discharge timing, dietary changes etc.). Pre-assessment
clinics are ideally multidisciplinary for more complex or older adults, to allow a
more holistic approach to patient care, whereas for less comorbid patients, nursing
pre-assessment may suffice. Pre-operative assessment should include: full medication review and risk of potential drug interactions, alcohol and drug history,
and identify sources of risk from omission of medications prior to surgery (e.g.
anticoagulants, or drugs used for glycaemic control).
Patient education prior to undergoing major surgery is essential. Importantly, a
survey in 2010 of ACPGBI members demonstrated that of 275 colorectal surgeon
participants, almost all patients (98%) received pre-operative written information
about ERAS principles, with verbal information provided to >98% of patients
across all hospitals [4]. The provision of relevant and timely information around
what the operation and recovery following surgery may entail, is important in
preparing patients psychologically for what they may experience [91]. Through
provision of multiple methods of communication regarding ERAS principles, there
is increased likelihood of retention of information, and may contribute to adherence with ERAS protocols and improved post-operative outcomes [43]. This also
may contribute to greater likelihood of shared decision-making, as patients become
more informed about differing treatment options, which may be of greater relevance in the high-risk setting [50, 83]. Shared decision-making is considered
the ‘gold standard’ of care, and aims to combine the ‘expert’ knowledge of both
patients and healthcare professionals to come to a mutual agreement on what treatment options are available, and ultimately selected [21]. Furthermore, a recent
review of patient education about recovery after colorectal surgery has suggested
that barriers may also include emotional situations and poor information design
(i.e. use of jargon, other confusing terminology) [17]. This is of particular importance in colorectal surgery, where stomal education may be necessary. Pre-emptive
education of patients with an introduction to stoma care nurses in the pre-operative
setting, rather than considering stomal education as a post-operative afterthought,
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can contribute significantly to reducing overall length of stay, increasing patient
confidence and fewer issues with leakage and stoma-related issues post-operatively
[18, 117].
Specific Considerations: Pre-operative Correction of Anaemia
Anaemia is a common condition found worldwide, with iron deficiency being the
commonest cause [102], with one in three patients at preassessment being identified as being anaemic [88]. The risk of iron deficiency anaemia may be even
greater in patients undergoing gastrointestinal surgery, where pathology such as
colorectal cancer may contribute to chronic blood loss or malnutrition [88]. Furthermore, chronic inflammation may disrupt iron metabolism pathways and lead to
greater levels of hepcidin which inhibits iron transport, thus negating the effectiveness of oral iron replacement due to a functional iron deficiency [29]. Pre-operative
anaemia is well-described to increase post-operative morbidity and mortality, the
risk of which does not seem to be reduced with the administration of red cell
transfusion [20, 26]. For example, van Halteren et al. demonstrated mortality was
three times higher in patients with rectal cancer with pre-operative anaemia [99],
with even mild anaemia increasing the relative risk of morbidity and mortality by
30–40% [8]. Complications are not limited to, but include: acute kidney injury,
stroke, infection, and anastomotic leakage [28, 46], leading to greater risk of critical care admission and length of stay [86]. Recent work has also demonstrated
pre-operative anaemia screening and treatment to be cost-effective [97]. Thus,
national guidelines exist to aid anaemia screening and inform the treatment of
pre-operative anaemia [41, 52]. An alternative to allogeneic blood transfusion, is
the administration of intravenous iron. This has been demonstrated to effectively
increase pre-operative haemoglobin [12, 42]. However, the recent PREVENTT
trial found that pre-operative iron administration did not reduce the need for intraoperative blood transfusion, and did not reduce the risk of post-operative mortality
[85]. Further research is needed to clarify the efficacy of various measures to treat
pre-operative anaemia in gastrointestinal cancer populations [12].
Specific Considerations: Smoking Cessation
Pre-operative smoking cessation may also improve post-operative outcomes. Carbon monoxide and p-nicotine contributes to reduced oxygen-carrying capacity,
reduced oxygen delivery, impaired collagen function and lung capacity, with
increased mucus production and a reduction in ciliary function. In combination,
this leads to increased cardiorespiratory complications and may impair wound
healing, contributing to surgical site infection and respiratory infection [72, 80]. In
an ideal world, smoking cessation should be commenced three to four weeks prior
to surgery, however some benefits may be seen within days [71, 92, 114]. Intervention in the pre-operative setting may also contribute to longer-term smoking
cessation, with clear benefits for patient health [96], with interventions including
individual counselling and nicotine replacement therapy.
7 Patient Optimisation for Colorectal Surgery 185
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Summary
Pre-assessment offers the opportunity to identify potential risk factors for complications, leading to their mitigation. These methods have been demonstrated to be
cost-effective and may be beneficial in contributing to patients overall health in
both the short and longer-term, should these contribute to long-lasting behavioural
change. Pre-assessment may also contribute to the process of shared decisionmaking between patients and healthcare professionals and may be delivered in the
outpatient setting through telehealth options or face-to-face.
7.2.2 Prehabilitation
The Cambridge dictionary defines prehabilitation as ‘activities done by someone
before they have a medical operation in order to improve their fitness and help
them to recover more quickly’ [14]. More specifically, prehabilitation aims to
optimise the patient during the time period leading into their next treatment and
those thereafter. In the rapidly evolving oncological pathway, colorectal cancer surgeons should consider prehabilitation prior to neo-adjuvant therapy and again in
the time period leading into their planned surgery. For patients undergoing elective
surgery for benign conditions (e.g., elective resection followed by stoma reversal), prehabilitation at several time points should be considered particularly as this
population are likely to have longer waiting lists in the current post-pandemic
climate [76]. Prehabilitation should be individualised and multimodal, including nutrition, exercise/physical activity (PA) and psychological support [60, 61].
However, these parameters are not confined and a colorectal surgeon might feel
their population needs additional parameters included in their prehab programme.
One example would implementation of geriatric expertise via the Comprehensive
Geriatric Assessment, (CGA) for frail older adults.
With an individualised approach, prehabilitation anticipates and aims to offset the deterioration in function after surgery displayed in Fig. 7.1. In greater
detail, Fig. 7.2 explains visually the functional improvements expected with prehabilitation that offset this predicted deterioration with the surgical stress response
[61]. Clearly enhanced recovery after surgery (ERAS) programmes have a role to
play in-hospital, but this deterioration still occurs. With prehabilitation, functional
capacity post-operatively remains close to the patient’s baseline at the time of their
diagnosis and remains greater than those patients that have not undergone prehabilitation, effectively anticipating and offsetting this expected decline. This proactive
complex intervention has been compared to training for a marathon where the similarities of individually and progressively overloading the body, leads to functional
improvements and improved running times [116]. Empowering the patient to take
control of their own treatment and implementing prehabilitation into the standard
colorectal surgical pathway is a significant movement away from the traditional
surgical pathway and requires resources and a culture change [11].
If prehabilitation can be implemented then it allows potentially long-term
lifestyle changes for each colorectal patient especially if integrated into the
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Fig. 7.2 From ‘Prehabilitation for people with cancer’
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prehab-into-rehab continuum where rehabilitation builds on the initial work of prehabilitation and ERAS programmes to allow a quicker recovery and an improved
quality of life for the patient Fig. 7.2.
7.3 The Evidence for the Effectiveness of Prehabilitation
7.3.1 Patient Safety and Feasibility
The majority of prehabilitation interventions have focused on patients with a cancer diagnosis. This large and vulnerable patient population are at greatest risk of
the complications discussed earlier, that may delay or interfere with future planned
treatment, making them a group that have a lot to gain from any prehabilitation
intervention success. One of the early criticisms of prehab was that it was unsafe
to put this vulnerable group through prehab, either physically or mentally with the
later focusing on the significant amount of information and appointments that each
patient has to process and organise. However, prehabilitation work during the last
ten years has shown that the safety profile of many of the reported interventions
rarely record any significant adverse events either in those patients going directly
to surgery or undergoing neoadjuvant therapy.
For direct-to-surgery patients, a recent systematic review supports the safety
and feasibility of performing a prehabilitation exercise intervention [66]. Encompassing a broad spectrum of exercise interventions (strength/ resistance training,
aerobic exercise, anaerobic exercise, yoga either in isolation or in combination) and
in different settings (home-based, supervised, group etc.). Different cancer populations were included (colorectal, oesophago-gastric, lung and prostate) to explore if
feasibility was different between such. The authors reported a high recruitment rate
87.7% (1371/1564) with 89.7% (1230/1371) completing the prehabiliation intervention. In regard to adverse events, no serious events (grade 3,4,5) were reported.
Patient acceptability was analysed in 5 reported studies and found to be 87.7% with
only one study significantly lower at 60%—reasons reported were that the patients
thought they were too weak to exercise or lived too far away to participate.
Neo-adjuvant therapy is widely reported to reduce functional capacity quantified by a reduction in cardiorespiratory fitness making this patient population
potentially vulnerable to any type of exercise intervention [58, 106]. West et al.
[107] prospectively recruited 39 patients (22 exercise and 17 control) upon completion of their neoadjuvant chemoradiotherapy. They were tested at baseline
(pre-neoadjuvant), week 0 (post-neoaduvant) then re-tested at week 6 after completing 6 weeks of structured responsive exercise training. Both groups physically
declined on CPET, however only the exercise group significantly improved after
completing prehabilitation showing that exercise focused prehabilitation is safe and
can produce improvements prior to surgery. Another study started prehabilitation
earlier, prior to starting neoadjuvant chemoradiotherapy and continuing through its
completion and up to the date for surgery [69]. With an excellent safety profile, an
individualised home-supervised walking intervention, prehabilitation was started
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before treatment and continued throughout until the time for surgery. The authors
reported recruitment rates of 61% (48/78), 75% adherence to the programme and
83% retention during the neo-adjuvant therapy and leading up to surgery. With a
mean intervention time of 14 weeks, prehabilitation in this setting could provide
the oncologist and surgeon with a potential opportunity to perform prehabilitation
without the time pressures of straight-to-surgery. In addition, it may minimise the
expected reduction in muscle mass seen with neoadjuvant therapy that places a
patient at greater risk of post-operative complications and a reduction in disease
free survival [70].
Another area of concern was the safety of performing physical and physiological assessments of potentially vulnerable patients. If we look at other vulnerable
patient populations there are reassuring positive examples, the main one being
the application of stress testing in patients with a suspicion or diagnosis of coronary artery disease [30]. Using either a bicycle or a treadmill, patients undergo
a graded exercise protocol that is monitored with electrocardiography and blood
pressure. Serious adverse events including myocardial infarction, sustained ventricular arrhythmia and death are rare with a risk of 1 in 10,000 patients reported.
Clearly there are contra-indications such as a recent acute myocardial infarction
and unstable angina, but these would also be contra-indications for immediately
starting neo-adjuvant therapy or planning urgent surgery for the colorectal patient.
7.3.2 Assessment of Prehabilitation
For the colorectal patient, there is no widely accepted functional test that should
be performed prior to prehabilitation. There are many available, all with a good
safety profile leaving the colorectal surgeon to choose what they think suits their
patient population, provides scientific and reliable measurements for their own
prehabilitation programme and what can be delivered within their local resources.
Assessments of functional capacity generally split into invasive or non-invasive,
from the scientifically objective and reproducible CPET (cardiopulmonary exercise
testing) to the more patient friendly stair climbing [36], sit-to-stand test, 6 minute
walk test (6MWT that give the output of the 6 minute walking distance, 6MWD)
[31, 68], Berg Balance Scale (BBS), Timed Up and Go Test (TUG), walking speed
[93] or grip strength using a dynamometer. Requirements vary with CPET needing
a specialist set up with cardio-respiratory equipment, blood lactate measurement/
and O2gas analyser and experienced exercise physiologists or anaesthetists
CO
2
to deliver. Whilst sit-to-stand test needs a chair and a stopwatch and the 6MWT
needs space (12.5 m or 25 m) marked out with cones and a stopwatch. They have
all been shown to be valid reproducible tests.
CPET carries the advantage of having scientifically developed specific cut offs
for morbidity, guiding the physiologist and the surgeon in assessment of risk for
the patient. West et al. [105] assessed 105 patients undergoing elective surgery
for rectal cancer (including 68 patients that had completed neo-adjuvant therapy).
Using ROC (Receiver Operated Characteristic) curves, they defined optimal cut
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off of 10.6 for lactate threshold and 18.6 mL/kg/ml for V02 peak. This group then
validated their findings in a multi-centre setting analysing 703 patients from 6 UK
centres [108]. Again, they reported an anaerobic threshold of 11.1 mL mL/kg/min
and V02 peak 18.2 mL/kg/min were associated with increased odds of in-hospital
2
morbidity after undergoing colorectal surgery. BMI over 27 kg/m
also carried
significantly higher morbidity whilst laparoscopic surgery decreased the risk of
complications.
For the non-invasive testing, the 6MWT (via distance, 6MWD) has been shown
to link to outcomes. This retrospective study assessed 459 patients with colorectal
cancer who had undergone TUG, handgrip strength, STS, 30 second arm curl test
and 6MWT [55]. Comparison of these functional capacity assessments to length
of post-operative stay found that only 6MWD of 432 m predicted 70% of patients
in the prolonged length of stay group (>3 days) (AUC 0.71, CI 0.63–0.78, p
= 000). For prospective evidence, good correlation between 6MWT and CPET
has been found (0.64–0.75) in studies including colorectal patients. In addition,
6MET predicted prolonged length of stay, severity of complications and disability free survival, but clear thresholds to define a high-risk patient remain unclear
[1, 13, 90, 112].
Nutrition and psychological assessment also provide a variety of validated
options that are not only safe, but easy to apply and lower in cost than the
functional capacity assessments. For nutrition, the British Association of Parental
and Enteral Nutrition (BAPEN) recommend the MUST [Malnutrition Universal
Screening Tool], [https://www.bapen.org.uk/screening-and-must/must]. Developed
by BAPEN in 2003, its simplicity has led to MUST being used widely in the
UK and beyond and being supported by NICE in 2012. For more research-based
assessments of nutrition, functional capacity measurements have been used such
as grip strength, gait speed or leg extension strength. For sarcopenia that has been
shown to be a poor prognostic factor in elective surgery in a recent meta-analysis,
Computed Tomography (CT) or ultrasound or dual-energy x-ray absorptiometry
(DEXA) can provide this information [24, 78]. Indeed, the colorectal surgeon may
find this easy to apply in the clinical setting as patients with cancer will already
have CT performed as part of the oncological staging pathway.
For psychological assessment, unsurprisingly there has been a focus in the cancer setting with the emotional response of patients to both the diagnosis and the
multiple investigations, treatments and follow up as a result. Examples of these
mental health difficulties (MHD) include anxiety, depression, panic and social isolation with 32% of patients affected [65]. There are many available questionnaires
to try to assess these MHD, including General Health Questionnaire (GHQ), Hospital Anxiety and Depression Score (HADS) and the ultra-brief 4-item patients
health questionnaire for anxiety and depression (PHQ-4) [54, 118]. The later was
supported by a recent publication from the Cancer Prehabilitation Implementation Steering group [15]. For older adults, the surgeon may want to consider the
quick Abbreviated Mental Test (AMT, AMT4 or AMT10) or perhaps the superior
Mini-Mental State Examination (MMSE) to assess mental impairment [45, 49].
The Montreal Cognitive Assessment (MoCA) is used widely for detection of mild
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cognitive impairment including early Alzheimer’s disease and for Delirium the
Confusion Assessment Method (CAM) is easy to learn and apply [48, 75].
All of these assessments for functional capacity, nutrition and psychology are
valid and feasible and have to be considered within the colorectal surgeon’s clinical
setting and available resources. As you will see from the next section, all are used
widely in the prehabilitation research and clinical setting.
7.3.3 Trials, Systematic Reviews and Meta-Analyses
Trials
One of the first randomised controlled trials on prehabilitation in colorectal patients
undergoing surgery was published by Carli et al. [16]. This exploratory study evaluated a structured prehabilitation regimen (stationary cycling plus weight training)
assessing the recovery of walking capacity compared to the control group (this
group received a recommendation to increase walking coupled with breathing
exercises). Using the 6MWT to assess walking capacity, the group reported a
recruitment rate of 75.6% (133/176) with 84.2% completing the full 3 data collections (baseline, pre-surgery, post-surgery). For the patients that were undergoing
surgery for cancer (the patient population had both benign and malignant indications for surgery), the mean duration of the prehabilitation period was 52 days
(interquartile range 22–60) supporting that prehabilitation could be implemented
into the cancer pathway despite the time pressures.
The key finding of this study was that there was no significant difference in
walking capacity (6MWT) between the two prehabilitation programmes. However, the control group (given advice about walking and breathing activity) had a
greater proportion of patients with a clinically meaningful improvement in 6MWT
in both the prehabilitation and the postoperative period (47% versus 22% in
cycling group). Several reasons are given for this including that the 6MWT is
specific to the walking group. However, other reasons include the low adherence
to both programmes and that the control group was potentially not a ‘standard
care’ control group with the walking and breathing programme giving the individual enough physiological overload to functionally improve, something that may
be further influenced by the group being non-blinded (‘exercise contamination’).
To overcome the limitations of poor adherence this group then re-analysed their
data including the people who completed the prehabilitation phase in either group
[63]. This reanalysis found that 33% improved their physical function with associated mental health improvements, vitality, self-perceived health and peak exercise
capacity. Furthermore, those patients who had improved with prehabilitation were
increasingly likely to have recovered to their baseline capacity than those with
no change or deterioration (77% versus 59% versus 32%; P = 0.0007). Overall,
this study showed promise for prehabilitation in colorectal surgery, but that more
evidence was required.
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Since then, there have been many studies showing functional capacity and
strength improvements with prehabilitation with many of the more recent publications preferring a multi-modal approach to prehabilitation with 2 or 3 prehab
components included in the interventional group. Several of these are now
discussed.
The time pressure to complete prehabilitation successfully in patients prior to
colorectal cancer surgery has been a widely expressed area of concern. Reassuringly the majority of studies have shown good recruitment and adherence. In
addition, prehabilitation has been found to be superior to rehabilitation, the later
often proposed as perhaps an easier time period to intervene in patients. In a randomized controlled trial conducted by Gillis et al. [33], it was demonstrated that
84% of patients who received a multimodal prehabilitation program prior to colorectal cancer resection recovered their baseline functional capacity by 8 weeks
post-surgery compared to only 62% of controls that received post-operative rehabilitation only The intervention was tri-modal with 3–4 weeks of home based,
unsupervised aerobic and resistance training >2 days/ week (50 min a week), whey
protein supplementation (to guarantee adequate daily protein intake) and general
dietary advice, anxiety reduction techniques (60 min with a trained psychologist followed by performing these techniques 2/3 week at home). Although it is
uncertain which component contributed the most to the improved functional outcomes, it is clear that complex interventions can be performed successfully in the
pre-operative period and that indeed, rehabilitation may be too late.
Recently published is The PREHAB Trial [67]. This international multi-centred
trial randomised colorectal patients (with no metastatic disease) to either 4 weeks
of prehabilitation or standard care (all sites included ERAS programmes). The
primary aim was to determine whether multi-modal prehabilitation could reduce
post-operative complications and enhance functional recovery. Compared to
standard care, number of severe complications was significantly lower in the
prehabilitation group (29.7% versus 17.1%, OR 0.47 (95%CI 0.26–0.87; p =
0.02). Functional capacity parameter favoured prehab in post-operative period,
but there was no significant difference in 6MWD between group at 4 weeks.
This programme consisted of 4 pillars: smoking cessation (at least 4 weeks);
exercise intervention (×3/week of a progressive in hospital high-intensity interval
training with upper and lower body training; plus walking or cycling for 60
minutes on days between supervised training sessions); dietary advice and protein
supplements (and vitamins) and 90 minutes of a psychologist visit (anxiety and
coping strategies; relaxation techniques).
For neoadjuvant treatment, EMPOWER was a multi-centred RCT in 5 UK
hospitals prehab versus usual care controls [57, 58]. For patients with margin
threatening rectal cancer, baseline testing was completed before neoadjuvant treatment and then after (post-treatment) then at weeks 3, 6 and 9. Prehabilitation
started post-treatment with 38 patients recruited (powered for 46). The prehab programme was 9 weeks duration with a high adherence of 91% (number of sessions
attended compared to number of sessions planned; a total of 27). Both groups
experienced physical fitness deterioration after neoadjuvant treatment, however,
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the prehabilitation group significantly improved their CPET results. Quality of life
was also assessed in this study with prehabilitation group only reporting a positive
effect. This work has led to the multi-centred WesFit trial that is underway [109].
Nutrition
Nutritional interventions are the most complex component of the multi-modal prehabilitation spectrum to report on. As a general approach, dietary advice can be
given where daily calorie count may need to be increased as part of the prescribed
aerobic and resistance exercise prehabilitation programme. Conversely, intentional
weight loss in overweight patients is a potential intervention with CARE trial
assessing [53].
More specifically, constituents of that daily calorie count may need to be modified to increase protein intake (whey powder, amino acid supplements) or fish oils
(krill) or vitamins (D or general multivitamins) [2, 34, 73, 98].
Novel dietary interventions can also be tested. One example is beetroot juice
which is a source of inorganic nitrate that has been implicated in development of
post-operative ileus, one of the commonest post-operative complications. A multicentre trial in Holland (BEET-IT) is assessing the reduction of ileus in patients
taking beetroot juice for one week prior to their colorectal surgery and completes
in 2025.
[https://clinicaltrials.gov/study/NCT05133024#publications].
Uni-modal prehabilitation can isolate a nutritional intervention to allow investigation and analysis, but with nutrition inherently linked to physical exercise and
activity, conclusions can be difficult to draw. Other complexities include: how
quickly can improvements be made within the prehabilitation time to surgery;
can the chosen measurements reproducibly detect those changes (weight, body
mass index, sarcopenia measurements from CT, blood markers); if more than
one nutritional intervention is chosen, how do they interact; and do nutritional
improvements link directly to post-operative outcomes for patients? Gillies et al.
[35] explored these questions in a scoping review that mapped the prehabilitation
literature to identify future research opportunities. They concluded that only 2%
of prehabilitation reported on uni-modal nutritional prehabilitation interventions
and that two thirds of all the published prehabilitation literature did not include
nutrition screening or assessment. For those that did, there was significant heterogeneity including no further monitoring of nutritional status and/ or use of
assessment tools that were not validated. This group proposed support for a core
outcome set in prehabilitation to overcome many of the limitations stated.
Psychological Interventions
With the move to multi-modal prehabilitation, it can be seen that psychological
interventions vary and can include anxiety management, relaxation techniques
and coping strategies. The results within these trials have been promising but
like exercise/activity and nutrition the underlying mechanisms and what the ‘best’
psychological intervention in what setting remains unclear.
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