Multidisciplinary Prehabilitation to Improve Frailty and Functional Capacity in High-risk Elective Surgical Patients: a Retrospective Pilot Study
Conditions: Frailty Syndrome
Sponsor: Chinese University of Hong Kong

Prehabilitation to improve frailty and functional capacity pilot study – English protocol ver 5            8 Dec 2022 
 
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Multidisciplinary prehabilitation clinic to improve frailty and functional 
capacity in high-risk elective surgical patients: a pilot retrospective 
observational study 
Henry MK Wong1, Calvin KW Kwong1, Bosco Ma5, Ding Qi5, Winnie Ng5, Stefanie Lam6, Terry Ting7, Kenny Ip8, 
Kelvin KC Ng4, Tony Mak4, HC Yip3, Samuel Yee3, Peggy PK Tsung1, SY Chan1, Gavin M Joynt2 
 
1Department of Anaesthesia and Intensive Care, Prince of Wales Hospital, New Territories, Hong Kong 
2Departtment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, New Territories, Hong Kong 
3Department of Surgery, Prince of Wales Hospital, Prince of Wales Hospital, New Territories, Hong Kong 
4Deparetment of Surgery, The Chinese University of Hong Kong, New Territories, Hong Kong 
5Department of Medicine and Geriatrics, Shatin Hospital, New Territories, Hong Kong 
6Department of Physiotherapy, Shatin Hospital, New Territories, Hong Kong 
7Department of Dietitian, Shatin Hospital, New Territories, Hong Kong 
8Department of Occupational Therapy, Shatin Hospital, New Territories, Hong Kong 
Correspondence should be addressed to Dr Henry MK Wong: mkw118@gmail.com 
 
Background 
Traditionally in surgical practice, the decision to proceed to surgery is made between the surgeons and the 
patients. Whenever necessary, the patients are sent to other specialties (eg. anaesthesiologists, physicians, 
dietitians, physiotherapists) for consultation and optimization before elective surgery. This approach is 
acceptable for the majority of fit patients, it can however be unsatisfactory for high-risk frail patients 
undergoing major surgical procedures. Hong Kong is facing an aging population. According to the 2016-based 
population projections published by the Census and Statistics Department, the pace of population aging in 
Hong Kong will keep on ramping up in the coming 20 years or so. Between 2018 and 2038, the size and share 
of the elderly population will almost double from 1.27 million and 17.9% to 2.44 million and 31.9% 
respectively1. With aging, there is an increase in frailty and a loss in functional and physiological reserve and 
adaptability, putting a patient that is exposed to a stressor, such as a major operation, at a higher risk of 
adverse outcomes2. Frailty is associated with two to six- fold increased risk of major adverse cardiac and 
cerebrovascular events, longer stays in intensive care unit and hospital, a 1-year mortality3. Pre-frail patients 
are also at risk of poor outcomes. Compared to non-frail patients, pre-frail patients (Clinical Frailty Score 4) 
had longer ICU stays, longer hospital stays, higher risk of postoperative stroke and a high risk of in-hospital 
mortality4. Malnutrition and sedentary lifestyle are common in frail elderly patients. These have been 
demonstrated to be a recognizable risk factor of poor postoperative outcomes11. It is therefore necessary to 
have a multidisciplinary team to manage frailty preoperatively. 
 
Prehabilitation is a multidisciplinary and multimodal approach involving anaesthesiologists, physicians, 
physiotherapists, occupational therapists and dietitians that aims to optimize functional capacity, nutritional 
status and emotional resilience before surgery, so as to enable the patients to better withstand perioperative 

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stress. It encompass individualized aerobic and resistance training to enhance cardiopulmonary fitness, 
dietary interventions to counteract the catabolic state of surgery, emotional support to improve resilience 
and advice on behavioural changes such as cessation of smoking and alcohol abuse. In the literature, 
prehabilitation has well been reported to enhance functional capacity before and after surgery. In particular, 
exercise training has been shown to improve various aspects of physical function of the frail elderly (eg. 
muscle strength, body composition, mobility, functional status and fall prevention)5. Tailored exercise training 
is therefore expected to improve physical fitness and increase functional capacity so that patients can better 
withstand the stress of surgery6. In a systematic review, prehabilitation before orthopaedic surgery have 
beneficial effects in improving strength, flexibility, balance and speed in 5 out of 7 randomized controlled 
trials7. Regarding postoperative clinical outcomes such as length of stay, readmission rate and postoperative 
complications rate, evidence demonstrated an association between physical fitness improvement and a 
lower rate and severity of complications8-9. Despite the heterogenicity in study design and modalities of 
prehabilitation program, the positive effect of prehabilitation on perioperative functional fitness has been 
shown across a wide variety of surgical procedures, including abdominal aortic aneurysm repair, 
esophagectomy, cystectomy, liver resection and colorectal surgery. In general, individuals who have been frail 
and having a sedentary activity level would benefit the most from prehabilitation program. Preoperative 
malnutrition can be due to inadequate intake and high requirements from the disease process that results in 
reduced body mass, strength and function and a reduced ability to mount an immunological defense. All 
these can be significant in the high catabolic state perioperatively for the healing process and the systemic 
inflammatory response to surgery. Preoperative malnutrition is associated with many adverse outcomes. 
After adjusting for active smoking status, preoperative malnutrition was associated with postoperative 
complications after pneumonectomy and hepatectomy12-13, a longer length of stay in hospital, higher 
readmissions within 28 days and a higher mortality up to 90 days after surgery14-16. Nutritional prehabilitation 
therefore helps prepare and optimize the patients’ nutritional status for surgery and recovery.  
 
The timing and duration of prehabilitation program can affect the risk of postoperative outcomes. An ideal 
duration of prehabilitation has not been established and there is a large heterogenicity in duration from the 
literature. But in general, a minimum of three to four weeks is required to have an effect of physical fitness17. 
Despite the need for novel resources, economic evaluation suggested that prehabilitation could be a cost-
effective approach10, the resulting benefits in short- and medium-term outcomes offset the costs of 
additional resources. 
 
Most of the “fast-track” surgical pathways focus on intraoperative and postoperative measures to enhance 
recovery, and the traditional rehabilitation approach is to operate first and then intervene. However, 
postoperative pain, fatigue and wound care impede the efficiency of rehabilitation measures such as 
physiotherapy and nutritional program. Therefore, it would be more ideal to start intervention before 
surgery while patients can be more actively engaged in the process of perioperative care and functional 
improvement. The earlier the patients can be engaged, the greater the likelihood of having a meaningful 

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impact and the less likely to affect the surgical schedule. The waiting time for surgery creates a window of 
opportunity to prepare the patients for prehabilitation by addressing problems of physical fitness, nutritional 
status and emotional distress. By re-engineering our preoperative assessment clinic and integration within 
the prehabilitation clinic, we are more able to risk stratify and identify high-risk patients at the time of 
preoperative evaluation. A common and one-stop platform can be shared by a multidisciplinary 
perioperative team with seamless communications, which reduces the chance of high-risk patients being 
bounced between independent consultations. 
 
Changing the present structure and logistics of preoperative assessment clinic requires active participation of 
the stakeholders involved in perioperative care. Surgeons need to refer patients to anaesthesiologists as 
early as possible for further screening into prehabilitation program. Anaesthesiologists need to have new 
assessment strategies for functional capacity that are not traditionally used in routine preoperative 
assessment clinic. Physiotherapist, occupational therapist and dietitians should ideally set up a one-stop 
service model to minimize patient travel. Effective implementation requires buy-in from hospital 
administrators, investing resources to support this value-based approach. Therefore, we will conduct a pilot 
retrospective observational study to evaluate the feasibility and impact of prehabilitation on our patients 
before major elective surgery. In particular, for the feasibility part, we aim to (1) estimate recruitment, 
attrition and adherence rate, and (2) ensure safety of prehabilitation. For the pilot part, we aim to identify if 
there are any changes on the outcomes after the prehabilitation intervention, and (2) identify estimates of 
variance for sample size calculation for future randomized trials. 
 
Materials and Methods 
Trial design 
This is a single centered, unblinded, single-arm retrospective study. 
 
Setting and preoperative care pathway 
The study is conducted at the Prince of Wales Hospital, a tertiary centre and a university teaching hospital 
with 1650 bed in Hong Kong. In the usual preoperative care pathway, referred patients are seen in 
preoperative assessment clinic. If the patients need medical optimization, consultations will be sent to 
corresponding medical specialty for further workup and assessment. Physiotherapy and dietitians referrals 
are initiated by surgeons at the time of decision for surgery. No adjustment is made between the schedule of 
surgery and the date to be seen at preoperative assessment clinic. Functional capacity assessment is based 
on subjective estimation of metabolic equivalent based on exercise tolerance. A metabolic equivalent of less 
than 4 and inability to climb 2 flights of stairs have been used to identify patients with poor functional 
capacity. There are no screenings for anaemia and malnutrition in the routine preoperative care pathway, 
and no preoperative interventions are prescribed to patients with baseline anaemia, malnutrition and poor 
functional capacity. 
 

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Prehabilitation clinic 
New preoperative care pathway has been implemented since August 2019. In the new preoperative care 
pathway (Fig 1), referred patients are screened by anaesthesiologists for inclusion into prehabilitation clinic, 
with the date of the clinic session at least 5 weeks before the estimated operation date. Eligible patients will 
have the baseline blood samples taken on the same day of clinic attendance. The blood samples include 
routine bloods plus the investigations necessary for anaemia screening (ferritin, iron profile, C-reactive 
protein, vitamin B12 and folate level). Anaemia is defined by the World Health Organization as a circulating 
haemoglobin concentration below 13g/dL for men and 12g/dL for non-pregnant women21. Patients found to 
have absolute iron deficiency anaemia (ferritin <30mcg/L, or ferritin <100mcg/L with transferrin saturation 
<20%) will be admitted to day surgery centre on the same day for a single dose of intravenous ferric 
carboxymaltose (20mg/kg for body weight <50kg, 1000mg for body weight >50kg) at least 3 weeks prior to 
the estimated operation date. The intravenous iron infusion will be given over 30 minutes under close 
monitoring. Patients will also be screened for malnutrition in the prehabilitation clinic using the Malnutrition 
Screening Tool (MST). Patients with MST score of more than one will be referred to dietitians for nutritional 
prehabilitation. Furthermore, functional capacity and frailty of patients will be assessed using Duke Activity 
Status Index (DASI) questionnaire, 6-mintue walk test (6MWT) and Clinical Frailty Scale (CFS). Patients with 
DASI score <34 or 6MWT distance <400m will be recruited into the prehabilitation program. 
 

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Fig 1. Workflow of prehabilitation clinic 
 
Exercise prehabilitation 
Collaboration was made with the Geriatric Day Hospital (GDH) of the same hospital cluster for the 
prehabilitation service. The GDH at Shatin provides a seamless one-stop service in medicine and geriatrics, 
physiotherapy, occupational therapy and dietitians. Patients screened eligible for recruitment are sent to 
GDH within one week after the prehabilitation clinic attendance for further holistic care and assessments. 
Patients will undergo a structured preoperative exercise training of 3 or more weeks, depending on the 
schedule of surgery, to optimize the physical and psychosocial fitness of patients with underlying frailty 
syndrome before surgery by physiotherapists at GDH. The result of the submaximal exercise test from the 
6MWT will be used as an estimation of individual peak oxygen uptake and hence oxygen uptake reserve 
(VO2R) for exercise prescription22. Each patient’s prehabilitation program will be individualized and symptom 
limited, in which exercise prescription and progression will be based on the results of the exercise test, 
individual health status, exercise performance and training response. Based on the American College of Sport 
Medicine guidelines on exercise prescription, the exercise protocol comprise of 75-90min of supervised 

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exercises at least twice per week (3 times per week for the first 2 weeks). There is a combination of 
moderate-intensity aerobic exercise and resistance training, with the exercise intensity 3-6 according to the 
modified Borg Scale. In the aerobic exercise, the patients will be asked to perform treadmill walking, stepping 
exercises and ergometer for 30min. For the resistance training, patients will be asked to perform 10 
repetitions per major muscle group of upper and lower limbs with at least 2 sets, depending on individual 
tolerance and performance. Home exercise program including stretching, aerobic and resistance training, 
and breathing exercises will be prescribed to patients with guided videos. Advice on smoking cessation and 
positive psychology support will be given to patients during the prehabilitation program. 
 
Nutritional care pathway for prehabilitation (Fig 2) 
Patients with MST score >=2 will be referred to dietitian at Shatin Hospital for nutritional prehabilitation. Two 
sessions of nutrition therapies will be offered to each eligible patient. The first session will be completed at 
4-week before the operation, and the second session will be given to the patient at 1-week before the 
operation. Assessments by dietitians include nutritional status assessment, anthropometric measurement, 
body composition analysis (muscle mass, percentage body fat), phase angle, and dietary intakes will be 
collected in each intervention. During the first and second intervention, energy level of 25-30kcal/kg/BW and 
protein level of 1-1.5g/kg/BW will be prescribed. During the second intervention, immunonutrition support, 
using a nutrition supplement containing arginine, nucleotides and omega-3 fish oil will be prescribed 5-7 
days prior to surgery to metabolically prepare the body cells for surgical stress. Patients with poor renal 
function, poor sugar control, and severely impaired liver function will be excluded for nutritional 
prehabilitation. 
 

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Fig 1. Nutritional care pathway for prehabilitation patients 
 
Inclusion and exclusion criteria 
We have procedure-specific and patient-specific criteria for inclusion. For procedure-specific criteria, we 
include major hepatectomy (resection of 3 or more Couimaud’s segments), pancreaticoduodenectomy, 
esophagectomy and radical cystectomy. For patient-specific criteria, we include adult patients age 50 or 
older, undergoing elective major procedures from the following surgical specialties (hepatobiliary and 
pancreatic, upper gastrointestinal, colorectal and urological), together with one of the following: 
1. 
American Society of Anaesthesiologists physical status (ASA-PS) score >=3 
2. 
Pre-frail to moderately frail patients with a Clinical Frailty Scale18 3-6 at time of assessment at 
prehabilitation clinic 
3. 
6-minute walk test distance < 400 metres 
4. 
Duke Activity Status Index19 < 34 
5. 
Malnutritional Screening Tool20 score >=2 
All patients are required to have an estimated 5 weeks or more of surgical waiting time to ensure the listed 
surgery date is compatible with an optimal prehabilitation time of 3 weeks or more17. 

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The exclusion criteria are: 
1. 
Patients with unstable angina or unstable cardiac syndrome (New York Heart Association Class IV, 
critical left main coronary disease, hospitalization for arrhythmias, congestive heart failure or acute 
coronary syndrome before assessment at prehabilitiation clinic) 
2. 
Patients with left ventricular outflow obstruction (severe aortic stenosis, hypertrophic cardiomyopathy) 
3. 
Chronic obstructive pulmonary disease GOLD stage IV 
4. 
Abdominal aortic aneurysm >8.0cm or suspected dissecting or leaking aortic aneurysm 
5. 
Cognitive deficits unable to comply with study procedures, physical limitations that would prelude 
rehabilitation and inability to regularly attend prehabilitation sessions. 
 
Data collection 
Frailty measures (CFS, 30 seconds sit-stand test, hand grip strength, time-up-and-go test) and functional 
capacity measures (6MWT distance, calculated peak oxygen uptake, DASI score) will be collected at 
prehabilitation clinic and upon first and last prehabilitation session. We will also evaluate the dose-response 
effect of the number of prehabilitation sessions attended. The cause for any premature termination of 
prehabilitation, for example, change in surgical plan or date, patient non-compliance, or logistic difficulties 
will also be analysed. Quality of life measurement using EQ-5D and emotional resilience screen using DASS-
21 will be done at the first and last prehabilitation session. Nutritional status based on measurement of 
weight, BMI, muscle mass and percentage body fat will be recorded at the first and last prehabilitation 
session. 
The following demographic data will be collected at baseline including age, gender, body weight, body mass 
index, ASA-PS, details of surgical procedures, length of hospital and ICU stay, pulmonary complications, 
discharge destination (home, hospital or nursing aged-care facility) and 30-day mortality from patient’s 
medical record.  
 
Table 1   Assessments overview 
Assessment 
Baseline First prehab 
session 
Last prehab 
session 
POMI 
Enrolment 
 
 
 
 
Eligibility screen 
X 
 
 
 
Demographic data 
X 
 
 
 
Comorbidity data 
X 
 
 
 
Primary outcomes 
 
 
 
 
6MWT 
X 
X 
X 
 
Secondary outcomes 
 
 
 
 
DASI 
X 
 
 
 
Clinical Frailty Scale 
X 
 
 
 

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Other frailty measures (Hand grip strength, 30s 
sit-stand test)  
 
X 
X 
 
DASS-21 
 
X 
X 
 
Nutritional status (muscle mass, % fat, BMI, 
weight) 
 
X 
X 
 
3-day food record 
 
X 
X 
 
Length of hospital and ICU stay 
 
 
 
X 
Pulmonary complications 
 
 
 
X 
30-day mortality 
 
 
 
X 
DAH30 
 
 
 
X 
 
Outcome measures 
Primary outcomes 
The primary outcome is the changes in the 6MWT distance and the calculated peak oxygen uptake (VO2peak) 
between baseline and upon completion of prehabilitation program. A dose-response effect on 6MWT 
distance and calculated VO2peak with regards to the number of prehabilitation sessions attended will be 
investigated. The 6MWT evaluates the ability of an individual to maintain a moderate level of physical 
endurance. Moderate to strong correlations have been found between the 6MWT and VO2peak obtained with 
other modes of exercise testing. Participants are instructed to walk back and forth a 30m stretch of hallway 
for 6min at a pace that would make them tired by the end of the walk. A change in 6MWT distance of 20m 
was considered meaningful as this is the estimated measurement error in community-dwelling elderly26. 
We will also assess the feasibility of the program by examining the recruitment, attrition and adherence of 
patients to the prehabilitation sessions. The reasons for drop-out from prehabilitation will be recorded. 
 
Secondary outcomes 
Secondary outcome measures include patient reported outcomes before and after the prehabilitation 
program. These include the followings: 
 
Emotional resilience 
The Chinese (Hong Kong) version of the Depression Anxiety Stress Scale (DASS-21) will be used as a measure 
of psychological stress25. It is widely used in the measurement of depression, anxiety and stress. This self-
reported questionnaire has three subscales corresponding to depression, anxiety and stress. Each of the 
three subscales includes 7 items. Patients are asked to rate each item on a 4-point scale (0 to 3) based on 
their experience during the past week. The scores on DASS-21 are multiplied by 2 to calculate the final 
subscale scores, producing a maximum of 42 points in each subscale. The higher the score, the greater the 
severity of depression, anxiety and stress. DASS-21 will be measured at baseline and upon completion of 
prehabilitation. 
 

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Nutritional outcomes 
Nutritional status before and after prehabilitation will be measured using body weight, BMI, muscle mass 
and percentage body fat. Dietary assessment will be performed using 3-day food record. Patients will be 
asked to record all foods and beverages consumed over a period of 3 days. The dietary intake adequacy 
relative to the expected individual requirement, the energy intake, and the amount of protein intake 
measured from the 3-day food record will be compared before and after prehabilitation. 
 
Clinical outcomes 
The length of hospital stay, in-hospital pulmonary complications, 30-day mortality and discharge destination 
(home, hospital or nursing aged-care facility) will be recorded. Pulmonary complications are defined using 
the NSQIP Definitions of Postoperative Complications (pneumonia, unplanned intubations, pulmonary 
embolism, failure to wean from the ventilator for more than 48 hours postoperatively) 
 
Others 
Other secondary outcome measures include the changes in hand-grip strength, time-up-and-go test and 30 
second sit-stand test before and after prehabilitation. 
 
Sample size and statistical analysis 
According to a randomized controlled trial published 2014 that addressed the effect of prehabilitation in 
patients undergoing colorectal resection for cancer27, the patients in prehabilitation group had their 6MWT 
distance significantly improved by 25.2m (SD 50.2) compared to baseline after 4 weeks exercise training, 
while those in control group declined by 16.4m (SD 46.0). Using a sample size calculator, a sample size of 46 
will achieve 80% power to reject the null hypothesis with an effect size of 0.86 and a significant level of 0.05 
using a 2-sided two-sample equal variance t-test. 
 
Data will be analyzed using SPSS 26.0 software (SPSS, Inc, Chicago, IL, USA). Continuous variables will be 
presented as mean +/- standard deviation or median +/- interquartile range if not normally distributed. The 
Shapiro-Wilk test will be used to check data for normality. Categorical data will be shown as numbers and 
percentages. Comparison of continuous data will be performed with Student’s t test with normal distribution 
and by Mann-Whitney U test for non-normally distributed data. Chi-square test will be used to compare 
groups with categorical variables. P value less than 0.05 is considered significant.  
 
Ethics 
Patients attended the prehabilitation clinic from August 2019 to November 2021 were included in this 
retrospective study. Data will be kept confidential in secure offices of the Department of Anesthesia and 
Intensive Care, Prince of Wales Hospital. Ethics approval will be obtained from the Joint CUHK-NTEC Research 
Ethics Committee. The study will adhere to local laws and the Declaration of Helsinki. 
 

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