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Early mobilization programme improves functional capacity after major

abdominal cancer surgery: A randomized controlled trial

Article  in  BJA British Journal of Anaesthesia · September 2017

DOI: 10.1093/bja/aex250

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 British Journal of Anaesthesia, 119 (5): 900–7 (2017)

doi: 10.1093/bja/aex250
Advance Access Publication Date: 13 September 2017
Clinical Practice

CLINICAL PRACTICE

Early mobilization programme improves functional

capacity after major abdominal cancer surgery: a
randomized controlled trial
E. P. M. de Almeida1, J. P. de Almeida2, G. Landoni3,*, F. R. B. G. Galas2,
J. T. Fukushima2, E. Fominskiy3, C. M. M. de Brito1, L. B. L. Cavichio1,
L. A. A. de Almeida1, U. Ribeiro-Jr2, E. A. Osawa2, M. P.E. Diz2, R. B. Cecatto1,
L. R. Battistella1 and L. A. Hajjar2,4
1
Rehabilitation Department, Instituto do Cancer, Hospital das Clinicas da Faculdade de Medicina da
Universidade de Sao Paulo, Sao Paulo, Brazil, 2Intensive Care Unit and Department of Anesthesiology,
Instituto do Cancer, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo,
Brazil, 3Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina
60, 20132 Milan, Italy and 4Department of Cardiopneumology, Instituto do Coracao, Hospital das Clinicas,
Faculdade de Medicina da Universidade de Sa ~ o Paulo, Sa
~ o Paulo, Brazil

*Corresponding author. E-mail: landoni.giovanni@hsr.it

Abstract
Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and
exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and
safety of a supervised postoperative exercise programme.
Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncol-
ogy surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme
based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary out-
come was inability to walk without human assistance at postoperative day 5 or hospital discharge.
Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilita-
tion care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P¼0.01), with an absolute risk
reduction of 22.2% [95% confidence interval (CI) 5.9–38.6] and a number needed to treat of 5 (95% CI 3–17). All patients in the inter-
vention group were able to follow at least partially the exercise programme, although the performance among them was rather
heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises.
Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible
and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact
on clinical outcomes is still unclear.
Clinical trial registration: NCT01693172.

Key words: rehabilitation; postoperative complications; neoplasms; early ambulation; exercise

Editorial decision: June 1, 2017; Accepted: July 4, 2017

C The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
V
For Permissions, please email: journals.permissions@oup.com

900
 Early mobilization after major abdominal cancer surgery
Editor’s key points
• Perioperative physical exercise is likely to improve post-
operative outcomes, but clear evidence is lacking.
• This study found that an early postoperative mobiliza-
tion programme was feasible in major cancer surgery
patients.
• Early mobilization group was associated with better
functional capacity, and perhaps better health-related
quality of life with less postoperative fatigue.
Major abdominal oncology surgery is a prototype of surgical
trauma that leads to a substantial loss of functional capacity,
particularly in elderly patients. Full recovery to a preoperative
state of independence may take weeks or even months.1
Although surgery is the cornerstone of treatment to many intra-
abdominal tumours, the decline in physical status caused by a
surgical procedure can postpone the initiation of other adjuvant
cancer therapies and impair the quality of life and patient
outcomes.2
Early postoperative mobilization has been advocated for
patients undergoing major surgery in order to improve functional
capacity and to enhance recovery. However, few studies focused
on demonstrating the benefits of postoperative exercise protocols
implemented in patients after major surgical procedures.3
Physical activity is associated with improvement in cardiopulmo-
nary endurance, decreased fatigue symptoms, improved muscu-
lar strength and quality of life.4 5 Despite potential benefits of a
structured postoperative rehabilitation programme, there is still
a lack of standardized postoperative rehabilitation protocols in
current guidelines of perioperative care.6
The aim of this study was to assess the effect, feasibility and
safety of an early postoperative mobilization programme on
functional capacity, quality of life and clinical outcomes in
patients undergoing major abdominal oncology surgery.
Methods
We performed a single-blind, parallel-arm, randomized trial in
patients undergoing major abdominal oncology surgery in a sin-
gle tertiary university hospital dedicated to cancer treatment.
The study was conducted in accordance with the International
Conference on Harmonization Good Clinical Practice and was
approved by the local ethics committee (Comitê de Ética e
Pesquisa da Faculdade de Medicina da Universidade de Sa ~o
Paulo, Brazil). Written informed consent was obtained from all
patients or their legal surrogate. The study protocol was regis-
tered at ClinicalTrials.gov as NCT01693172.
Study population
We screened patients older than 18 yr scheduled to undergo
elective major abdominal surgery for cancer treatment and
managed perioperatively conforming to enhanced recovery
principles as detailed in the Supplementary material. Major
abdominal oncology surgery was defined as a procedure involv-
ing the gastrointestinal, gynaecological or urinary tract with an
expected duration greater than 90 min. Exclusion criteria are
detailed in the Supplementary material.
All patients were assessed for eligibility on the eve of surgery
by a physician specialized in physical medicine and rehabilitation
| 901
(physiatrist) who analysed the ability to walk without assistance,
muscle strength and lack of neurological or cardiovascular condi-
tion, which would preclude exercise. Written informed consent
was obtained.
Randomization
Eligible patients were randomly assigned in a 1:1 ratio to one of
the two postoperative exercise programmes: an early postopera-
tive programme based on supervised aerobic exercise, resistance
and flexibility training or a standard rehabilitation care. The med-
ical staff contacted the study randomization centre to register the
patient and to be told which group the patient was allocated to.
To avoid loss of concealment, the group to which the patient was
allocated could only be accessed after registration in the study
randomization centre. Allocation numbers were derived from a
computer-generated non-blocked random number list prepared
by the chief statistician, placed in opaque envelopes and opened
sequentially to determine the treatment group of the patient. The
patients, outcome adjudication committee and the investigators
who classified outcomes and conducted the follow-up telephone
assessments were blinded to the study-group assignments and
had no access to the groups of treatment.
Assessment before exercises
Before and during the period of exercises, all patients included
in the study were assessed daily by the physiotherapist regard-
ing core stability, stability at orthostatic position, and upper and
lower extremities grade of muscle strength. Core stability was
defined as the ability of the patient to sit erected for at least
1 min. Stability at orthostatic position was defined as the ability
of the patient to stand up (without support or swaying) for at
least 1 min without development of symptoms of impending
syncope (e.g. light-headedness, dizziness and nausea) or hae-
modynamic changes (heart rate increase >30 beats min–1 above
supine baseline or by a systolic blood pressure decrease of
>20 mm Hg). Muscle strength was graduated according the
Muscle Strength Grading Scale (Grade 0 to 5).7
Treatment protocol
The early mobilization programme consisted of a set of exer-
cises (core stability and orthostatic training, gait training, aero-
bic and resistance training) implemented according to the level
of functionality or mobility of the patient (Fig. 1). The pro-
gramme started from postoperative day (POD) 1 and lasted until
hospital discharge with two sessions every day. A complete
description of the treatment protocol is in the Supplementary
material and in a concise form represented in Fig. 1.
Standard care
The standard rehabilitation care was composed of a set of exer-
cises that started on POD 1 and continued until hospital dis-
charge or walking independence. The programme was
performed once a day and consisted of core control training,
orthostatic training for patients with total core control and
lower extremity muscle strength grade >3, gait training and
passive or active range of motion exercises.
Outcome measures
The primary outcome was defined as the inability to cross the
room or to walk the distance of 3 m without human assistance,
 902 | de Almeida et al.

ASSESSMENT Muscle
Core stability
strength
assessment
assessment

No No
TRAINING FES
Muscle
Core stability? Core training Passive and
strength >3?
active ROM

Yes Yes
TRAINING Lower No Orthostatic
Exercise
extremities training-board,
tolerance
muscle stand-in table
training
strength >3? or aids

Yes

TRAINING Aerobic
Isometric Isotonic
Gait training training
training training
(Cyclo ergometer)

Core training Core training consisted in transferring patients to a sitting position with forearms resting on the bed and feet flat
on the floor, Thus, under physiotherapist supervision, patients were instructed to perform trunk flexion, trunk
extension, trunk lateral flexion and trunk circles, repeated 10 times, with the physiotherapist support if
necessary.

Gait training Gait training was performed in all patients with total core control, lower and upper extremity muscle strength
grade >3. Patients practiced walking over the ground with a physiotherapist, using walking aids if necessary.
The training progressed by increasing the speed and decreasing the reliance on walking aids.

Isometric training The isometric muscle contractions lasted 3 s and were increased according to patient tolerance. Isometric exercises
consisted of 3 sets of 10 repetitions each.
Isotonic training The isotonic resistance exercises were performed with a 1 kg or 2 kg weight, 3 sets composed of 10 repetitons each one.
Progression of weight from 1 kg to 2 kg occurred when patients could complete the resistance exercises with
1 kg weight with mild exertion.

Aerobic training Aerobic training was performed using the cycle ergometer during 20 min or two sets of 10 min, without
exceeding 80% of the maximum heart rate. Maximum heart-rate was calculated according to the Karvonen
Method.

Fig 1 Algorithm of the exercise protocol of the early mobilization group. ROM, range of motion; FES, functional electrical stimulation.

at POD 5 or at hospital discharge.8 The assessment of the ability
to ambulate was performed by an outcome assessor who was
not aware of the patients’ group assignment. Cross the room
and walk 3 m are interchangeable because 3 m is the distance
necessary to cross the room in the centre of the study. We pre-
dicted that readiness for discharge would be expected to be
reached after 4–5 days after a non-complicated abdominal sur-
gery based on previous studies and in our database.9
Secondary outcomes were: functional walking capacity
measured by the 6 min walk test (6MWT); incidence and inten-
sity of fatigue measured by the Piper fatigue scale revised (PFS-
R); health-related quality of life measured by EuroQol-5D-5L
survey; and reduction in lean body mass measured by the thigh
circumference at POD 5. We also measured the incidence of
postoperative complications using the Clavien–Dindo classifica-
tion, health-related quality of life by EuroQol-5D-5L 30 days after
surgery and hospital length of stay. We also investigated deep
venous thrombosis, delirium and exercise-related adverse
events (falls, pain, wound dehiscence, syncope, postural hypo-
tension) as post hoc endpoints. The outcomes definition is in the
online Supplementary material.
Statistical analysis
We estimated that 45% of our patients would not achieve the
primary outcome at POD 5 based on previous studies reporting
that 40% of patients were not able to walk one week after a
major abdominal surgery.1 We hypothesized that the early
mobilization programme would reduce the absolute risk of the
primary outcome by 25% when compared with the standard
rehabilitation programme. We calculated that a sample size of
108 patients would be required with 80% power to detect this
difference in a two-sided test, at a 5% level of significance.
 Early mobilization after major abdominal cancer surgery | 903

We compared the baseline characteristics, follow-up meas- Results

ures and clinical outcomes on an intention-to-treat
basis according to the randomized study-group assignment.
Continuous variables were analysed using a t-test or the Mann–
Whitney U-test, and categorical variables were compared
using Pearson’s v2 test, Fisher’s exact test or a likelihood ratio
test.
Continuous data are expressed as mean with standard devi-
ation (SD) or median with interquartile range (IQR). The primary
outcome is reported as relative risk with 95% confidence inter-
val (CI). We compared baseline characteristics and clinical out-
comes based on intention-to-treat principle. A two-sided P-
value less than 0.05 was considered statistically significant. The
statistical analyses were performed using SPSS version 18.0
(SPSS Inc., Chicago, IL, USA).
Study population
A total of 231 patients were scheduled for elective abdominal
surgery for cancer at the Cancer Institute of Sao Paulo between
January 2015 and September 2015. After exclusion according to
selection criteria, 108 patients were enrolled (54 to the early
mobilization programme and 54 to the standard rehabilitation
care; Fig. 2). There were no exclusions after randomization or
loss of follow-up and all enrolled patients were analysed for the
primary outcome.
Baseline characteristics of the patients were well balanced
between groups (Table 1). In both groups, lower gastrointestinal
tract was the most frequent primary cancer site, followed by upper
gastrointestinal tract and genitourinary system. Consequently, the

Assessed for elegibility (n=231)

Excluded (n=123)

Inability to perform preoperative 6 MWT

Randomized (n =108)
(prolonged preoperative fasting, bowel
preparation, pain, major comorbidity) (n=76)
Palliative procedures (n=34)
Postoperative invasive mechanical ventilation
more than 24 h (n= 3)
Declined to participate (n=3)
Participation in another research protocol (n=3)
Chronic kidney disease requiring RRT (n= 2)
Active infection (n=1)
Musculoskeletal and neurological conditions
(n=1)

Allocation
Allocated to early mobilization group (n =54) Allocated to standard care group (n=54)

Received allocated intervention (n = 54) Received allocated intervention (n =54)

Did not receive allocated intervention (n =0) Did not receive allocated intervention (n=0)

Follow-up

Lost to follow-up (n = 0) Lost to follow-up (n=0)

Discontinued intervention (n= 0) Discontinued intervention (n=0)

Analysis
Analysed (n=54) Analysed (n=54)

ITT Analysis (n =54) ITT Analysis (n=54)

Fig 2 Flow diagram of the study. 6MWT, 6 min walk test; RRT, renal replacement test; ITT, intention to treat.
 904 | de Almeida et al.

Table 1 Baseline demographic data and preoperative character- Table 2 Characteristics related to the underlying malignancies
istics. *Values are expressed as median (IQR); †NRS with score of patients and types of surgical procedure. Values are
of 3 or more means patient at nutritional risk. ECOG, Eastern expressed as number of patients (%). HIPEC, hyperthermic
Cooperative Oncology Group; ASA, American Society of intraoperative peritoneal perfusion with chemotherapy
Anaesthesiologists risk score; NRS, Nutritional Risk Screening
Variable Standard Early
Variable Standard Early care mobilization
care mobilization (n¼54) (n¼54)
(n¼54) (n¼54)
Type of tumour (%)
Age (yr)* 62 (51–68) 61 (53–70) Upper gastrointestinal 6 (11.1) 9 (16.7)
Male (%) 22 (40.7) 21 (38.9) Lower gastrointestinal 40 (74) 32 (59.2)
BMI (kg m2)* 25 (23–28) 25 (22–27) Pancreas 3 (5.6) 3 (5.6)
ECOG (%) Liver and biliary tract 0 (0) 2 (3.7)
0 29 (53.7) 25 (46.3) Urogenital 3 (5.6) 8 (14.8)
1 24 (44.5) 28 (51.9) Other (adrenal and peritoneum) 2 (3.7) 0 (0)
2 1 (1.8) 1 (1.8) Type of procedure (%)
Karnofsky* 90 (80–100) 90 (90–100) Upper gastrointestinal 6 (11.1) 7 (13.0)
Extent of cancer (%) (gastrectomy)
Metastatic (%) 12 (22.2) 12 (22.2) Lower gastrointestinal (abdomi- 27 (50) 26 (48)
Tobacco use (%) 3 (5.6) 2 (3.7) noperineal rectal amputa-
Hypertension (%) 27 (50.0) 22 (40.7) tion, colectomy and pelvic
Diabetes (%) 12 (22.2) 7 (13.0) exenteration)
Hypothyroidism (%) 1 (1.8) 6 (11.1) Urogenital (radical hysterec- 2 (3.7) 3 (5.6)
Chronic obstructive 2 (3.7) 2 (3.7) tomy, cystectomy, nephrec-
pulmonary tomy and ureterectomy)
disease (%) Pancreas, liver and biliary tract 15 (27.8) 13 (24.1)
Cirrhosis (%) 0 (0) 2 (3.7) (hepatectomy, pancreatec-
Acute myocardial 1 (1.8) 1 (1.8) tomy and
infarction (%) duodenopancreatectomy)
Heart failure (%) 0 (0) 1 (1.8) Peritonectomy (with or without 3 (5.6) 5 (9.3)
Atrial fibrillation (%) 0 (0) 1 (1.8) HIPEC)
Creatinine >1.5 mg dl1 (%) 1 (1.8) 0 (0) Other 1 (1.8) 0 (0)
Neoadjuvant therapy (%) 30 (55.6) 22 (40.7) Surgical technique (%)
ASA I (%) 3 (5.6) 7 (13.0) Laparoscopy 13 (24.1) 11 (20.4)
ASA II (%) 43 (79.6) 31 (57.4) Epidural analgesia (%) 45 (83.3) 44 (81.5)
ASA III (%) 8 (14.8) 16 (29.6)
Nutritional Risk Screening
(NRS 2002) (%)
1 7 (13.2) 10 (18.5)
2 30 (56.6) 24 (44.4)
3 13 (24.5) 15 (27.8) group, mainly because of resistance and aerobic training. At
4 2 (3.8) 4 (7.4) POD 1, 52% of patients in the interventional group managed to
5 1 (1.8) 1 (1.8) perform exercises using weights of 1 or 2 kg. This proportion
Subjective Global Assessment increased to 86% at POD 5. At POD 1, 46.6% managed to perform
(NRS 3)† (%) the aerobic training using the cycle ergometer, with a mean of
Well nourished 3 (6.0) 4 (7.0) 11.4 min per day. At POD 4, this proportion increased to 73%,
Moderately malnourished 13 (24.0) 16 (30.0) with a mean of 10.5 min per day. At POD 5, only 2% of the inter-
Preoperative serum albumin 3.8 (3.3–4.1) 4.1 (3.8–4.4) ventional group patients were not able to perform the gait train-
(g dl1)* ing (Supplementary Figs S1 and S2).
Preoperative haemoglobin 12.6 (11.4–13.3) 12.4 (11.6–13.9) There were three cases of protocol deviation in the early
(g dl1)* mobilization group; one patient started the exercise pro-
gramme on POD 2 and two patients performed the exercises
only once a day in one day during hospitalization. Overall
adherence to the early mobilization protocol was 94.4%.
Nevertheless, the performance among them was rather hetero-
most common procedures were surgeries involving the lower gas- geneous as many patients performed partially the exercises,
trointestinal tract, such as colectomy, rectosigmoidectomy and particularly in the first postoperative days (Supplementary Fig.
total pelvic exenteration. Of the 28 patients undergoing hepatec- S1). There was no protocol deviation in the standard rehabilita-
tomy or pancreatectomy, 20 patients were metastatic cancer tion group. Patients who had a severe postoperative complica-
undergoing metastasis resection. The main surgical technique tion during hospitalization, such as haemodynamic instability,
used to access the peritoneal cavity was laparotomy in both requirement of invasive mechanical ventilation or other severe
groups and the main anaesthetic technique was general anaesthe- clinical condition, which precludes them of performing exer-
sia combined with epidural anaesthesia (Table 2). cises, had the exercises withheld in both groups until clinical
The amount of exercise performed by the patients allocated stabilization. We did not consider such occasions as protocol
to the early mobilization group was greater than the control deviation.
 Early mobilization after major abdominal cancer surgery | 905

Table 3 Primary and secondary outcome measures. *Values are expressed as median (IQR); †Pearson v2; ‡Mann–Whitney; ¶Fisher’s exact
test. RR, relative risk; CI, confidence interval

Variable Standard care Early mobilization P-value RR (95% CI)

(n¼54) (n¼54)

Primary outcome
Inability to cross the room without 21 (38.9) 9 (16.7) 0.010† 0.42 (0.22–0.85)
human assistance (%) 95% CI (25.9–53.1) 95% CI (7.9–29.3)
Secondary outcomes
6 min walk test (m)*
Preoperative 391 (317–435) 403 (350–451) 0.31‡ –
Postoperative day 5 66 (0–228) 212 (56–299) 0.004‡ –
Length of hospital stay (days) 8 (7–13) 8 (6–13) 0.25‡ –
Delirium postoperative (%) 2 (3.7) 0 (0) 0.50¶ –
Deep vein thrombosis (%) 0 (0) 1 (1.8) 1.000¶ –
Thigh circumference (cm)*
Preoperative 47 (44–50) 46 (44–49) 0.56‡ –
Postoperative 46 (42–50) 46 (42–49) 0.66‡ –

Primary outcome
Table 4 Incidence of preoperative and postoperative fatigue
At POD 5, 16.7% of patients in the early mobilization programme according to revised Piper Fatigue Scale (PFS) >0. *Values
were not able to cross the room or walk 3 m without human expressed as median (IQR); †Pearson v2; ‡Fisher’s exact test;
¶
assistance compared with 38.9% in the standard rehabilitation Mann–Whitney. The PFS has four subscales, which assess four
group (P¼0.01; Table 3). Patients in the early mobilization pro- dimensions of fatigue: sensory, affective, cognitive-emotional,
gramme group had an absolute risk reduction for the primary and behavioural-intensity. The PFS total score and its subscale
scores range from 0 to 10. Values are expressed in number of
outcome of 22.2% (95% CI 5.9–38.6) and a number needed to treat
patients (%) or median (IQR)
of 5 (95% CI 3–17) in comparison with the standard group.
Variable Standard Early P-value
Secondary outcomes care mobilization
(n¼54) (n¼54)
At POD 5, performance in the 6MWT was greater in the early mobi-
lization programme group when compared with the standard reha- Piper – total (%)
bilitation group [212 m (56–299) vs 66 m (0–228), P¼0.004; Table 3]. Preoperative 4 (7.4) 7 (13.0) 0.34†
Also, patients in the early mobilization programme group Postoperative 19 (35.2) 9 (16.7) 0.028†
had a lower incidence of fatigue at POD 5 compared with the Piper – behavioural (%)
standard group (Table 4), and of those who presented fatigue, it Preoperative 3 (5.6) 7 (13.0) 0.18†
was less intense in the early mobilization group (Supplementary Postoperative 19 (35.2) 9 (16.7) 0.028†
Table S1 and Fig. S3). Piper – affective (%)
Health-related quality of life at POD 5 was better in the early Preoperative 3 (5.6) 5 (9.3) 0.72‡
mobilization group compared with the standard rehabilitation Postoperative 18 (33.3) 9 (16.7) 0.046†
group. However, there was no difference between groups regard- Piper – sensory (%)
ing quality of life 30 days after randomization (Supplementary Preoperative 4 (7.4) 7 (13.0) 0.34†
Fig. S4 and Table S2). Postoperative 19 (35.2) 9 (16.7) 0.028†
Piper – mood (%)
There were no differences regarding postoperative complica-
Preoperative 4 (7.4) 7 (13.0) 0.34†
tions assessed by the Clavien–Dindo classification (Table 5) as
Postoperative 19 (35.2) 8 (14.8) 0.015†
well as no difference in the incidence of delirium and deep
Piper – cognitive (%)
venous thrombosis. The median hospital length of stay did not
Preoperative 4 (7.4) 7 (13.0) 0.34†
differ significantly between groups (Table 3). A post hoc analysis
Postoperative 15 (27.8) 7 (13.0) 0.056†
suggested that in some patients the intervention facilitated early Fatigue duration, days*
discharge (length of stay 7 days was recorded in 14.8% in the Preoperative 0 (0–0) 0 (0–0) 0.33¶
control group and in 33.3% in the intervention group, P¼0.024). Postoperative 0 (0–5) 0 (0–0) 0.068¶
About the causes of deaths, two patients in the intervention
group died at the hospital as a result of surgical complications—
both patients had refractory septic shock—one after obstructive
acute abdomen (POD 25) and the other after evisceration (POD
28). Two patients of the control group died after hospital dis-
Discussion
charge of unknown causes.
We did not observe any difference between groups in safety In this study involving 108 patients who underwent major
outcomes, such as the occurrence of falls, pain, wound infec- abdominal cancer surgery, an early mobilization programme
tion, syncope, dehiscence and postural hypotension requiring based on supervised exercises performed twice daily was feasi-
vasopressors (Supplementary Table S3). ble and superior to standard postoperative rehabilitation,
 906 | de Almeida et al.
Table 5 Clavien–Dindo postoperative complications. Values are
expressed as number of patients (%). *Likelihood Ratio test. †All
patients had at least Grade I that included minor risk events
not requiring therapy (with the exceptions of analgesic, antipy-
retic, antiemetic, diuretics drugs, electrolytes and also includes
wound infections opened at the bedside). Grade II complica-
tions were defined as complications requiring pharmacological
treatment with drugs other than such allowed for Grade I com-
plications (blood transfusions and total parenteral nutrition are
also included); Grade III complications were defined as compli-
cations requiring an invasive procedure (IIIa not under general
anaesthesia; IIIb under general anaesthesia); Grade IV compli-
cations defined as life-threatening complications requiring
Intensive Care Unit admission and advanced organ support
(IVa single organ dysfunction, including dialysis, and IVb multi-
organ dysfunction); Grade V complication indicated death of a
patient. POD 30, postoperative day 30
Variable Standard Early P-value
care mobilization
(n¼54) (n¼54)
Clavien–Dindo 0.48*
POD 30 – Grade (%)†
I 34 (63) 37 (68.5)
II 12 (22.2) 10 (18.5)
IIIa 0 (0) 1 (1.8)
IIIb 4 (7.4) 4 (7.4)
IVa 2 (3.7) 0 (0)
IVb – –
V 2 (3.7) 2 (3.7)
resulting in a greater proportion of patients able to walk without
human assistance on the fifth day after surgery. Patients in the
early mobilization group also performed better than the usual
care group on secondary outcomes, such as 6MWT, health-
related quality of life, incidence and intensity of postoperative
fatigue.
To our knowledge, this is the first randomized study show-
ing that an intensive postoperative rehabilitation programme
improves functional capacity in cancer patients. A previous
study10 with 77 patients undergoing colorectal resection for can-
cer showed that a prehabilitation protocol increased functional
walking without impact in clinical outcomes. These findings
associated with our data reinforce the importance of stimulat-
ing both the preoperative and the postoperative rehabilitation
in cancer patients to acquire functional improvement in the
context of cancer care.
An ability to walk across the room or 3 m on the fifth postop-
erative day or at hospital discharge was selected as the primary
outcome because such a measure is recognized to be an impor-
tant functional outcome after high-risk surgery and is likely to
evaluate factors such as aerobic capacity and muscle strength.8
There are other tools already validated to evaluate functional
capacity as the 2, 6 and 12MWT, and timed-up and go test. In
our study population, there are no previous data addressing
which is the most appropriate test.
Our findings are consistent with previous studies that eval-
uated the effect of an early mobilization strategy on the func-
tional capacity of patients undergoing major surgery.11 However,
most studies have evaluated the early mobilization strategy as
part of a set of interventions in a multidisciplinary rehabilitation
approach, known as fast-track or enhanced recovery after
surgery (ERAS), which limits the measurement of the impact of a
postoperative exercise protocol on functional capacity and other
outcomes.3 12 13 The ERAS interventions have demonstrated to
be effective in promoting reduction in mortality, morbidity and
hospital length of stay in different surgical populations, and are
considered standard of care.14–18 Nevertheless, these studies are
heterogeneous and postoperative mobilization protocols are
poorly described.3 6 The novelty of our study is that we could
compare a programme of early mobilization with a standard
rehabilitation care and evaluate its impact on functional capacity
inside the frame of ERAS, as our institutional protocol of perio-
perative care had already incorporated most of the characteris-
tics of the ERAS programme.
Our study has strengths such as high adherence to the post-
operative exercise programme, which is greater compared with
other studies mainly because we overcome classic barriers to
postoperative mobilization. We involved a multiprofessional
approach including oncologists, surgeons, physiotherapy pro-
fessionals, nurses and physiatrists in a supervised protocol and
we implemented a strategy of preoperative education of
patients, focusing in information and discharge planning. Also,
other strengths should be mentioned such as the strict supervi-
sion of the intervention and performance tests by a health pro-
fessional; utilization of a validated tool to assess postoperative
complications (Clavien–Dindo); utilization of previously vali-
dated tools for health-related quality of life and fatigue assess-
ments (EuroQoL-5D-5L and Piper); and the evaluation of safety
outcomes.
As limitations of our study we should mention that it is a
single-centre study performed in a reference centre for cancer,
with physiotherapists available 24 h a day, which limits the gen-
eralization of our results. However, this could have contributed
to the high adhesion rate to the protocol. In addition, our results
underscore the importance of supervised exercises after oncol-
ogy surgery because of its positive impact on functional capacity
recovery. We also have to mention that the applicability of the
protocol was restricted to those who presented a reasonable
preoperative functional level and 76 of 231 patients screened
were not included in the study because of an inability to per-
form the preoperative 6MWT. Furthermore, the number of
patients who had neoadjuvant treatment was higher in the
standard group than in the early mobilization group and this
could have influenced the results of the study; however, when
we adjusted the primary outcome analysis for this variable, we
still found a difference between groups (Supplementary
Table 4S). Also, patients were not submitted to pulmonary func-
tion tests, which would be an objective method to measure the
effect of the postoperative exercise protocol on pulmonary
capacities; and the fact that, although all patients have under-
gone abdominal surgery, patients had different tumours and
therefore were submitted to different procedures. Another
important limitation is that our study was not designed and
powered to evaluate postoperative clinical outcomes. However,
we highlight the importance of demonstrating that a supervised
intensive exercise protocol is feasible and safe in a subset of
cancer patients undergoing surgery. Physiotherapists were not
blinded to the intervention and one can argue this fact as a limi-
tation, but blindness in this context was not feasible because of
the nature of the intervention. To attenuate this limitation, out-
come assessors were not aware of the assigned group. We also
mention as a limitation of our study that secondary outcomes
should be interpreted with caution because adjustment for mul-
tiple comparisons was not performed; therefore, applying a P-
value threshold of 0.05 may lead to an alpha error.
 Early mobilization after major abdominal cancer surgery
Conclusion
An early postoperative mobilization programme based on a set
of exercises, such as core stability and orthostatic training, gait
training, aerobic and resistance training, implemented twice
daily, seems to be safe, feasible and improves functional
capacity compared with a standard rehabilitation care in
patients undergoing major elective abdominal oncology surgery.
However, its impact on clinical outcomes is still unclear.
Authors’ contributions
Had full access to all of the data and takes responsibility for the
integrity of the data and the accuracy of the data analysis:
E.P.M.de.A.
Study concept and design: E.P.M.de.A., J.P.de.A., F.R.B.G.G. and
L.A.H.
Acquisition, analysis or interpretation of data, final approval of
the version to be published, and agreement to be accountable
for all aspects of the work thereby ensuring that questions
related to the accuracy or integrity of any part of the work are
appropriately investigated and resolved: all authors.
Drafting of the manuscript: E.P.M.de.A., J.P.de.A., G.L., E.A.O. and
L.A.H.
Critical revision of the manuscript for important intellectual
content: C.M.M.de.B., U.R.-J., M.P.E.D., L.R.B., E.F. and J.T.F.
Statistical analysis: J.T.F. and E.F.
Administrative, technical or material support: L.B.L.C.,
L.A.A.de.A., R.B.C. and E.F.
Study supervision: E.P.M.de.A. and L.A.H.
Supplementary material
Supplementary material is available at British Journal of
Anaesthesia online.
Declaration of interest
The authors have no conflicts of interest to declare related to
this manuscript.
Funding
This study was performed at the Instituto do Cancer, Hospital das
Clinicas da Faculdade de Medicina da Universidade de Sao Paulo,
Sao Paulo, Brazil. The study was sponsored by the University of
Sao Paulo. There was no funding source for this study.
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Handling editor: Paul Myles