Effect of Postoperative Oral Carbohydrate Administration in Total Knee Arthroplasty Elderly Patients
Phase: EARLY_PHASE1
Conditions: Total Knee Arthroplasty, Postoperative Oral Carbohydrates, Postoperative Recovery, Elderly Patients
Sponsor: Nanjing First Hospital, Nanjing Medical University

Protocol version: October 16，2022
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PROTOCOL
Effect of Postoperative Oral Carbohydrate Administration in Total Keen Arthroplasty
Patients
October 16,2022

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Effect of Postoperative Oral Carbohydrate Administration in Total Keen
Arthroplasty
1. Research background
In recent years, the concept of accelerated rehabilitation surgery (enhanced recovery
after surgery, ERAS) has developed vigorously, using a series of optimized
evidence-based medical support with preoperative, intraoperative and postoperative
programs to reduce postoperative physiological and psychological stress trauma
response, so as to achieve the goal of accelerating patient rehabilitation[1].
Perioperative fasting water ban management is an important component of ERAS.
Studies have found that prolonged preoperative drinking and fasting will increase the
postoperative insulin resistance, cause hypertension, and increase the risk of
postoperative infection, which is not conducive to the postoperative recovery of [2].
Oral carbohydrates for at least 2h before anesthesia can reduce the perioperative stress
response, improve patient comfort and satisfaction, and promote the postoperative
rehabilitation of [3]. The [4] of the Chinese Expert Consensus and Path Management
Guide for Accelerated Rehabilitation Surgery (2018 edition) advocates the early
postoperative recovery of diet. Studies have shown that the early recovery of oral
eating, drinking water and early oral assisted nutrition after elective abdominal
surgery can promote the recovery of intestinal motor function, help to maintain
intestinal mucosa function, prevent microflora imbalance and displacement, and can
reduce the incidence of postoperative infection and shorten the postoperative
hospitalization time by [5]. At present, shortening the perioperative water fasting time
needs to be concentrated in the preoperative stage. Although the guidelines and a
small number of studies recommend the early recovery of diet after surgery, there is
no clear stipulation on the recovery time of postoperative diet and drinking water, and
most domestic hospitals still perform fasting for at least 6h after surgery.
Carbohydrates are perioperative good oral nutritional fluids. In recent years, studies
have shown that preoperative oral carbohydrates can not only supplement the lost
water and energy, improve their thirst and hunger, but also improve the postoperative
metabolism and stress changes, reduce postoperative insulin resistance, shorten the
hospital stay, and accelerate the [6] recovery of patients compared with clear water.
Furthermore, preoperative oral carbohydrate has been confirmed by many studies and
does not increase the risk of reflux aspiration in [7]. However, most of the current
clinical studies of oral carbohydrate effects on postoperative recovery focus on the
preoperative oral phase, and only a few small samples have shown that postoperative
oral carbohydrate improves postoperative comfort [8]. Therefore, further systematic
studies on the effects of early postoperative oral carbohydrates on postoperative
recovery remain lacking.
Directory of reference
[1] Miller TE, Roche AM, Mythen M. Fluid management and goal-directed therapy as
an adjunct to Enhanced Recovery After Surgery (ERAS). Can J Anaesth. 2015
Feb;62(2):158-68.

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[2] Rizvanović N, Nesek Adam V, Čaušević S, Dervišević S, Delibegović S. A
randomised controlled study of preoperative oral carbohydrate loading versus fasting
in
patients
undergoing
colorectal
surgery.
Int
J
Colorectal
Dis.
2019
Sep;34(9):1551-1561. doi: 10.1007/s00384-019-03349-4. Epub 2019 Jul 15. PMID:
31309323.
[3] Nygren J, Thorell A, Ljungqvist O. Preoperative oral carbohydrate therapy. Curr
Opin Anaesthesiol. 2015 Jun;28(3):364-9. doi: 10.1097/ACO.0000000000000192.
PMID: 25827282.
[4] Surgery Branch of Chinese Medical Association, Anesthesiology Branch of
Chinese Medical Society. Chinese Expert Consensus and
Path Management
Guidelines for Accelerating Rehabilitation Surgery (2018) [J]. Chinese Journal of
Anesthesiology, 2018,38 (001): 8-13.
[5] Yang R, Tao W, Chen YY, Zhang BH, Tang JM, Zhong S, Chen XX. Enhanced
recovery after surgery programs versus traditional perioperative care in laparoscopic
hepatectomy: A meta-analysis. Int J Surg. 2016 Dec;36(Pt A):274-282. doi:
10.1016/j.ijsu.2016.11.017. Epub 2016 Nov 10. PMID: 27840308.
[6] Bethune Orthopaedic Accelerated Rehabilitation Alliance, Bethune Charity
Foundation
Orthopaedic
Professional
Committee
of
trauma,
Joint
Surgery
Professional Committee of Bethune Charity Foundation, etc. Guidelines for the
management of perioperative fasting fasting in orthopaedic surgery [J]. Chinese
Journal of Trauma and Orthopedics, 2019,21 (10): 829-834.
[7] MD Smith,
Mccall J , Plank L , et al. Preoperative carbohydrate treatment for
enhancing recovery after elective surgery[J]. Cochrane Database Syst Rev, 2014,
8(8):CD009161.
[8] Noba L , Wakefield A . Are carbohydrate drinks more effective than preoperative
fasting: A systematic review of randomised controlled trials[J]. Journal of Clinical
Nursing, 2019, 28.
[9] Wang Cuilan, Huang Yuting, Zeng Qing, et al. Study on postoperative fasting
water prohibition time under ERAS concept [J]. Clinical Medical Engineering,
2022,29 (4): 2.
1. Study purpose and study endpoint
1.1 Study Purpose

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1.1.1 Main study objective: To evaluate the effect of oral carbohydrates early after
TKA on the nutritional status of elderly patients.
1.1.2 Secondary study objectives: To evaluate the effect of early oral carbohydrate
administration on the comfort and safety of
TKA in elderly patients.
1.2 Study endpoint
1.2.1 Primary study endpoints
Pre-albumin levels in venous blood in the fasting state on the day of surgery, 1d and
3d after surgery.
1.2.2 Secondary study endpoints
1.2.2.1, Effectiveness study endpoint
1) The level of retinol-binding protein in venous blood on the day and 1d and 3d after
surgery;
2) The insulin resistance index in venous blood was checked on the empty stomach on
the morning, 1d and 3d after the operation;
3) NRS score of thirst and hunger at 2h, 6h and 8h after surgery;
4) Abating distension within 24h after surgery;
5) The incidence of hypoxemia and reflux aspiration within 24h after surgery;
6) Time of anal exhaust for the first time after surgery;
7) Time to leave bed for the first time after surgery;
8) Length of hospitalization;
9) Postoperative subject satisfaction score.
1.2.2.2. Safety study endpoint
1) The incidence and severity of various adverse events (AE) from the start of oral
carbohydrates to the end of the trial;
2) The incidence and severity of adverse events such as nausea, vomiting and
hypoxemia from the first start of drug administration to the end of the trial;
3) Number of antiemetic drugs used within 24h after the first start to the first start of
drug administration;
2. Expected results
Oral carbohydrates in the early postoperative period can improve patient nutritional

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status, improve comfort and satisfaction without increasing the incidence of adverse
events.
3. Design and method of the study
3.1.1 Screening period
Patients with elective knee replacement, screened with informed consent to enroll
patients, met all enrollment criteria and did not meet any of the exclusion criteria.
3.1.2 Treatment Period
Actively control blood pressure, blood pressure and blood sugar, correct anaemia and
hypoproteinemia, and increase protein intake before surgery. The dietary plan was
informed by the ward nurse: all patients were fasted with solid food 6 hours before
surgery and took 200 milliliters of carbohydrates orally 2-3 hours before surgery.
The venous access was open after home invasion and was routinely monitored
electrocardiogram(ECG),
non-invasive
blood
pressure(NBP)
，
oxygen
saturation(SpO2)，bispectral index (BIS). Parecoxib 40 milligrams of analgesia was
given intravenously at 30 minutes before the start of the procedure.
Adductor
canal block （ACB）and
Infiltration between poplitealartery and capsuleof knee
(IPACK ) block were performed on the lower limbs of the surgical side using an
ultrasound high-frequency line array probe before induction of the general anesthesia
procedure.
Anesthesia induction: after static injection of Midazolam 0.03 milligrams / kilogram,
Propofol 2 milligrams / kilogram ，
Sufentanyl 0.4 milligrams / kilogram,
Cisatracurium 0.2 milligrams / kilogram. The tracheal tube was inserted after
3minutes and mechanical controlled ventilation was performed mechanical controlled
ventilation, fraction of inspired oxygen（FiO2）40%, oxygen flow 2 litres/ minutes,
minute ventilation 7 milliliters / kilogram, respiratory rate （RR ）12 times/
inspiration-to-expiratory ratio（I: E）1:2, maintain partial pressure of carbon dioxide in
endexpiratory gas （PETCO2）35-40 millimeters of mercury（mmHg）. Anesthesia
maintenance: intravenous propofol 4~7 milligrams / kilogram/ hour, remifentanl
0.3-0.5 microgrammes/kilogram/ hour, maintain BIS 40~60. A restrictive fluid
management strategy was adopted, with 6ml/ kg·h supplemented with physiological
needs, blood loss was supplemented with hydroxyethylstarch fluid, and concentrated
red blood cells were infused at hemoglobin (Hb) <80 grams / litre to maintain patient
blood pressure and heart rate fluctuations less than ±20% of the basal value .
Dexamethasone 5mg and totoxetron 2mg for prophylactic antiemesis were given
intravenously
at
30min
before
the
end
of
the
surgery. All
patients
used
hydromorphone patient-controlled intravenous analgesia （PCIA ）
pump for
continuous: 1ml / h, automatic control: 5ml, locking: 10min, limit: 35ml / h, adjust
parameters according to the pain.
Internal postanesthesia care unit（PACU）management: Patients will randomly enter

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the PACU into two study groups: early carbohydrate feeding group (EOF group) and
conventional feeding group (control group). Routine feeding group (Group C):
Patients in group C were observed with 60min of abnormal vital signs after extubation,
and returned to the ward for fasting and fasting for at least 6 h, and began to eat
gradually through the mouth after anal exhaust. Early carbohydrate feeding group
(EOF group): The EOF group drank 10.5% of 5 ml/kg body weight (100ml containing
12.5g maltodextrin, fructose and glucose) after extubation in the resuscitation room.
PACU management: Patients will randomly enter the PACU into two study groups:
early carbohydrate feeding group (EOF group) and conventional feeding group
(control group). Routine feeding group (Group C): Patients in group C were observed
with 60min of abnormal vital signs after extubation, and returned to the ward for
fasting and fasting for at least 6 h, and began to eat gradually through the mouth after
anal exhaust. Early carbohydrate feeding group (EOF group): The EOF group drank
10.5% of 5 ml/kg body weight (100ml containing 12.5g maltodextrin, fructose and
glucose) after extubation in the resuscitation room.
To evaluate the drinking criteria for patients in the EOF group: Steward wake score of
6 and wake level level 3, take 5 ml/kg body weight of 12.5% carbohydrate (100ml
containing 12.5g maltodextrin, fructose, and glucose) according to the patient's
consent. The process of drinking carbohydrates was to take 30ml orally first. After
observing the swallowing without abnormality, the patient was ordered to drink the
remaining drinks within 2h. After the patient returned to the ward, the liquid diet
began to gradually overenter the normal diet. When the patient was able to tolerate the
normal diet, v.
Evaluation process of the drinking index:
1. Steward score: Akefulness: 0-no response to stimulus; 1-some response to stimulus;
2-full awake.(2) Respiratory tract patency degree: 0 points-the patient's respiratory
tract needs support; 1 points-the patient's respiratory tract can maintain patency
without support; 2 points-the patient can cough according to the doctor's guidance.(3)
Body activity degree: 1 points-the patient's limb has no activity; 2 points-the patient's
limb has an unconscious activity; 3 points-the patient's limb can carry out conscious
activities
2. Wakefulness classification according to the patient's consciousness performance:
Level 0: the patient is completely asleep, Call without any response; Level 1: The
patient is falling asleep, However, head and neck movement, eye opening or limb
movement when breathing; level 2: the patient is awake, Have the same performance
as level 1, At the same time can also open the mouth, stretch the tongue; Level 3: The
patient is awake, Have the same performance as level 2, At the same time can also
clearly say their own name, age and other information; Level 4: The patient is awake,
Have the same performance as level 3, It can also accurately identify the surrounding
environment, And tell you exactly where you are.
3. In addition to receiving different feeding treatment programs in the PACU, the two
groups received the same care and diet program formulated by the same care group.
3.1.3 The Follow-up Period
Record: Patients had fasting serum prealbumin, retinol-binding protein levels, and

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insulin resistance index on the same day, 1day and 3 days after surgery.
Record: 2 hours, 6 hours and 8 hours postoperative digital scores; bloating,
hypoxemia and reflux aspiration occurred 24 hours after surgery.
Record: length of hospitalization, first anal exhaust time, first ambulation time, nausea
and vomiting, and patient satisfaction.
4. Subject recruitment and protective measures
4.1 Inclusion criteria

Patients undergoing elective knee replacement surgery;

the patient gave informed consent;

Age ≥65 years, Sex is not limited

American Society of Anesthesiologists(ASA)Ⅰ~Ⅲlevel

Body Mass Index(BMI)18~28kg/m2
4.2 Exclusion criteria

Preoperative gastric emptying disorders, such as gastroesophageal reflux or
previous surgery;

Diabetes mellitus, severe renal insufficiency, or other severe metabolic diseases;

History of motion sickness;

Mental disorders, alcoholism, or a history of substance abuse;

Patients with abnormal swallowing function;

Maltodextrin, fructose allergy or intolerance;

Surgery time was greater than 3 hours.
4.3 Exit criteria
Patients may withdraw their informed consent and withdraw from the trial at any
time.
The investigator may decide on the subject to terminate the withdrawal from the study
in the following circumstances.
Any medical condition in the study leads to the risk of continuing the study subjects;
Subjects receive analgesic treatment other than the prescribed analgesic remedy
protocol, and other subjects who fail to complete the test as specified in the test
protocol;
The investigator judged the other conditions that should be withdrawn from the trial.
5 Informed consent
5.1 The Informed Consent Form
The informed consent was in accordance with the ethical principles outlined in the
Declaration of Helsinki. The informed consent form detailed the study protocol and
process, and fully explained the risks of the study.
The informed consent form also states that the records of the individual identity must
be kept confidential, but the research team and regulators can access the subject
information.
5.2 Informed consent process and record
Informed consent begins before the individual consent to participate in clinical studies
and continued throughout the course of the clinical study.
5.3 Confidential
Personal patient information will be given as confidential information. All patient data

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obtained from the patient cases will be kept as confidential. Patients will be identified
by their name acronym and the numbers provided at the time of study inclusion.
Patients or their families will be aware of the anonymity of the data and their right to
protect their privacy. However, it is also important to understand the fact that the data
will be submitted to the subject responsible unit or the government management
authority, and may also be submitted to institutions such as the Ministry of Health for
inspection and evaluation. The participating physician will keep a list of patient
personal data (patient data and corresponding patient names) for confirmation of the
record.
6. Quality control and quality assurance
6.1 Qualification of research unit and researcher qualification
The research unit shall have the experience in drug research, the facilities and
conditions of the department where the project belongs shall meet the needs of safe
and effective clinical research, and the researchers shall have the professional
expertise, qualifications and ability to undertake the clinical research, and shall be
trained in GCP regulations.
6.2 Training of the researchers
Before the start of the study, the research leaders of each center should organize the
researchers to study the program, and only the researchers who have passed the
program training can participate in the study to ensure that the researchers have a
consistent understanding of the protocol. For important assessment scales, relevant
personnel in the participating centers need systematic training and even obtain
corresponding qualification certificates.
6.3 Surveillance of clinical trials
The hospital ethics committee and institutional review board may conduct a
systematic review of the clinical trial-related activities and documents, to evaluate
whether the trial was conducted in accordance with the test protocol, SOP, and
relevant regulations, and whether the test data are timely, true, accurate, and complete
records. The audit should be performed by those who do not directly involve the
clinical trial.
7. Organization and management of the research
7.1 Change of the scheme
All additional or referenced appendices are integral parts of the scheme. No one shall
make any modifications or revisions to any part of the research protocol, as signed by
the investigator and the principal of the project, unless these changes or revisions have
been fully discussed. And through the unanimous consent of the researcher and the
subject leader.
Any agreed modifications will be recorded and will be signed by the investigator and
the project leader and filed with the protocol.
7.2 Retention of the records
The investigator shall keep all the detailed original documents of the subject and
record the trial process, medication status, laboratory examination data, safety data
and efficacy assessment in the case report form. The recorded data shall be complete,
timely and clear. The original documents and medical records should be clear, detailed

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and easily identified by those participating in this clinical trial.
The case report form and the original files can only be modified by the investigator.
No modification to the case report form and the original file shall smear the original
data off. The correct way to modify is to line the original data, and then write the
modified data next to the original data, and sign the date and the name of the
modification.
Test data shall be retained until 5 years after the termination of the test.
7.3 Early termination of the study
The leader of the project decides to stop or interrupt the study in advance in the case
of force majeure, and should inform the doctors involved in the study in writing.
Similarly, any participating unit that decides to withdraw from the study for any
reason should also notify the project leader in written form.
7.4 Research, supervision and inspection
7.4.1 Research supervision
Inspectors must follow the drug clinical trial quality management specification (GCP)
and standard operation procedures (SOP), visit the research unit regularly or
according to the actual situation, supervise the clinical trial work and progress, check,
confirm all data records and reports, correct and complete, consistent with the original
data, ensure the clinical trial in accordance with the clinical trial protocol, the
researchers should actively cooperate with the inspectors. The specific contents of the
inspector include:
a) Ensure that the test undertaking unit has appropriate conditions, including staffing
and training, complete laboratory equipment, good operation, various inspection
conditions related to the test, an estimated sufficient number of subjects, and the
participants to be familiar with the requirements in the test plan;
b) Monitor the implementation of the trial program during the trial, confirm that the
informed consent of all subjects is obtained before the trial, understand the enrollment
rate of the subjects and the progress of the trial, and confirm that the selected subjects
are qualified;
c) Confirm that the records and reports of all data are correct and complete, and that
all case report forms are entered correctly and consistent with the original data. All
errors or omissions have been corrected or indicated, signed and dated by the
Investigator.
d) Verify that all adverse events are recorded, and that serious adverse events shall be
reported and recorded within the specified time;
e) Clearly and truthfully record the failed visits, unconducted tests, and undone checks
should be made, and whether the errors and omissions should be corrected;
f) The written inspection report shall be completed after each visit, which shall state
the date, time, name of the inspector, the findings of the inspection, etc.
7.4.2 On-site inspection
The responsible unit may conduct an on-site inspection of the research at a clinical
research institution. The audit includes the required test documents, records of the
informed consent process, and the consistency of the eCRF and the original
documents. But also the content and scope of the inspection can be increased

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according to the situation. The investigator agrees to participate at a reasonable time
and in a reasonable manner.
8. Investigators' responsibilities
8.1 Participation of doctor responsibilities
The participating physicians will conduct the study following the study protocol and
confirm the accuracy of the data entered. The participating physicians should be
responsible for obtaining written signed informed consent for data collection from the
study subjects.
8.2 Responsibility of the project leader
The project leader takes all reasonable steps and provides sufficient resources to
ensure the implementation of the research, mainly involving the following aspects:
a) Ensure that the study complies with relevant national and local regulations,
including ethical requirements, patient data protection regulations, etc.
b) Ensure the effectiveness of quality control and analysis of research results.
9. Share results
The intellectual property rights, trial data and research results related to this study are
jointly owned by Nanjing First Hospital and the Department of Anesthesiology.
The intellectual property rights, trial data and research results related to this clinical
study are owned by Nanjing First Hospital and the Anesthesiology Department.
10. Ethics principles and requirements for clinical research
Clinical research will follow the world medical congress "declaration of Helsinki" and
the national health and family planning commission of the People's Republic of China
"involving people biomedical research ethics review method" and other relevant
provisions, the specific implementation of informed consent, the privacy protection,
research free and compensation, risk control, special subject protection and research
related damage compensation principles and requirements. The clinical study was
performed before the ethics committee approved the trial protocol. Before each
subject is enrolled in the study, the investigator has the responsibility to present the
subject or / and his legal agent about the purpose, procedures of the study and possible
risks, and sign a written informed consent form that their participation in the clinical
study is completely voluntary, that they may refuse to participate or withdraw from
the study at any time at any stage of the trial without discrimination and retaliation,
and their medical treatment and interests are not affected. The informed consent form
should be retained as a clinical research document for future reference to effectively
protect the subjects' personal privacy and data confidentiality.