Efficacy of Perioperative Anesthesia Care Bundle on Prognosis in Elderly Undergoing Hip Fracture Surgery: a Single-center Randomized Controlled Trial
Phase: NA
Conditions: Anesthesia, Hip Fracture Surgery, Nursing
Sponsor: Second Affiliated Hospital of Wenzhou Medical University

 
Efficacy of Perioperative Anesthesia care bundle on 
Prognosis in elderly undergoing Hip Fracture Surgery: 
a single-center randomized controlled trial 
Acronym: EPAPHUS 
 
PRAMARY INVESTIGATOR： TING LI 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 
ORGANIZATION'S UNIQUE PROTOCOL ID：SAHOWMU-CR2017-03-110 
Version Number：1.0  
CENTER：THE SECOND AFFILIATED HOSPITAL AND YUYING CHILDREN’S HOSPITAL OF WENZHOU MEDICAL 
UNIVERSITY 
STATISTICIAN：THE SECOND AFFILIATED HOSPITAL AND YUYING CHILDREN’S HOSPITAL OF WENZHOU 
MEDICAL UNIVERSITY, CLINICAL RESEARCH CENTER 
2018-1-29 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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Study summery  
Title 
Efficacy of Perioperative Anesthesia care bundle on Prognosis in 
elderly undergoing Hip Fracture Surgery: a single-center randomized 
controlled trial 
Objectives  
1.To evaluate the efficacy of perioperative anesthesia care bundle on 
prognosis in elderly undergoing hip fracture surgery. 
2.To assess the levels of compliance that current anesthesia 
management strategy of our hospital against the new “guidelines”. 
3.To analyze the defects in the current anesthesia management 
strategy and collect data for further multi-center research. 
Study setting  
The Second Affiliated Hospital and Yuying Children’s Hospital of 
Wenzhou Medical University 
Study design  
Prospective, single center, randomized controlled clinical trial. 
Study subjects 
Elderly patients with acute hip fracture on one side and need surgical 
treatment 
Inclusion criteria 
1.Patients ≥ 75 years old; 
2.Patients with hip fracture purely and surgical treatment is scheduled. 
Exclusion criteria 
1.surgical treatment has been performed after entering hospital; 
2. Multiple trauma: multiple fractures; chest, abdomen, pelvis and sacral 
trauma; severe head injury, etc. 
3.Refuse to sign informed consent; 
4. Investigator thinks he/she is inappropriate to carry out this study. 
Study grouping 
1.New “guideline” anesthesia strategy team (Group A)  
2.Current anesthesia strategy team (Group B) 
Primary outcome 
Mortality in 6 months of postoperative 
Secondary outcomes 
1.The intensity of postoperative pain using Visual Analogue Scale (VAS) 
2.The incidence of postoperative complications  
3.Mortality for postoperative of 30 days and 1 year 
4.Length of time after surgery to death 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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5.The level of compliance of new “guideline”(from the ratio of (score:total 
score)) 
6.Length of hospital stay 
7.Total cost in hospital and expenditure for anesthesia  
8.Cognitive function with Mini-Mental State Examination (MMSE) 
9.Overall satisfaction of patients 
Statistical analysis 
See the statistical analysis scheme 
Expected length of progress Two years 
Background 
Hip fracture is commonly seen among elderly patients. The incidence of hip fracture in the aged 65 and 
older is 957.3: 100,000 and 414.4: 100,000 respectively. Most of the elderly hip fracture needs surgical 
treatment, and the operation can improve the prognosis of patients. The 30-day hospitalization death 
rate for non-surgical treatment patients was twice as high as those with surgical treatment. However, 
elderly hip fracture patients always combine a variety of systemic diseases such as cardiovascular 
diseases (35%), respiratory system diseases (14%), cerebrovascular disease (13%), diabetes (9%), 
malignant tumor (8%) and kidney diseases (3%), and about 70% of patients are Ⅲ ~ Ⅳ class of 
American Society of Anesthesiologists (ASA). Their death rate in 6 months of postoperative is still 
between 12%~23% according to the survey, and 6 ~ 15 times higher than elective hip replacement. 
 
A meta-analysis combines 35 observational studies describes that early surgery (operates within 48 
hours) may reduce the risk of postoperative death, odds ratio (OR) = 0.74, with 95% confidence interval 
(CI): (0.67, 0.81). In addition, the risk of complications such as lung infection or deep vein thrombosis 
can be significantly increased by missing the best surgical time. But observational studies cannot tell 
whether a patient has an operation delay due to illness, which in turn affects mortality. This study has 
reviewed more than 1000 patients in our hospital (complete the operation within 48 hours) and found a 
mortality of 27% (low), and the mortality after operation within one month is 0.5%; while the length of 
surgery over 48 hours, mortality at 3.5% within one month after operation. So further randomized 
controlled studies are needed. 
 
A retrospective study in the United States involving 18158 patients found that compared with general 
anesthesia, regional anesthesia reduces the inpatient mortality and pulmonary complications, but the 
continuation of studies (involving 56729 patients) found that local anesthesia does not decrease inpatient 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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mortality and pulmonary complications, only slightly reduced the length of hospital stay (published in the 
journal JAMA).The effect of anesthesia on the prognosis of hip fracture remains to be confirmed by further 
randomized controlled study. 
There are researches that adopted a system of perioperative multidisciplinary management strategy that 
can significantly reduce the mortality of six months after hip fracture, and also lower the stress ulcer, 
occupancy rate of ICU and hospital readmission rate within 30 days. 
 
The anesthesia research associated with hip fracture have the following several noteworthy viewpoints: 
(1) Whether new drug xenon (NCT01199276) or low doses of intraoperative sedation (NCT00590707) 
can reduce the occurrence of postoperative delirium. (2) Whether Dexmedetomidine is useful to the 
postoperative treatment. (3) Whether the best analgesia method is nerve block (NCT01593319, NCT 
1547468 and NCT01638845). (4) Whether perioperative nutrition management can improve the outcome. 
(5) Anesthesiologists may need more effective clinical evaluation method than ASA to predict the 
prognosis. But as an important medical treatment for the perioperative period of elderly hip fracture, 
anesthesia needs to improve the management strategy of itself in order to improve its prognosis. A single 
anesthetic method or measure may not be sufficient to affect its prognosis. 
 
On April 10th, 2017, the Chinese medical association anesthesiology branch introduced the Chinese 
elderly hip fracture patients’ anesthesia and perioperative management guidelines (hereinafter referred 
to as "guidelines"), which expounds anesthesia related management strategies for these patients 
systematically and comprehensively. This study conformed to the guidelines and combined with our 
clinical practice, as a result, the measures to "improve" summarized (see appendix 1). The clinical 
anesthesia management strategy will implement in accordance with the appendix 1. Therefore, the 
purpose of this study is to compare the effect of the new "guideline" with the actual clinical anesthesia 
management strategy of our hospital on the prognosis of recent elderly hip fracture. 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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Its significance lies in: (1) The results of this study can be a preliminary answer whether new version of 
"guidelines" can improve the recent prognosis of elderly hip fracture, and the necessity of the promotion 
for the new "guidance". (2) The level of compliance of anesthesia management strategy from our hospital 
with new “guideline”. (3) Analyzing whether the present defects of anesthesia management strategy exist, 
and collect data for further multicenter study. 
References： 
1. 
Moja L, Piatti A, Pecoraro V, Ricci C, Virgili G, Salanti G, Germagnoli L, Liberati A, Ban  G: Timing 
matters in hip frac- ture surgery: Patients operated within 48 hours have bet- ter outcomes. A meta-
analysis and meta-regression of over 190,000 patients. PLoS One 2012; 7:e46175 
2. 
Neuman MD, Silber JH, Elkassabany NM, Ludwig JM, Fleisher LA: Comparative effectiveness of 
regional versus general anesthesia for hip fracture surgery in adults. ANESTHESIOLOGY 2012; 
117:72–92 
3. 
Neuman MD, Rosenbaum PR, Ludwig JM, Zubizarreta JR, Silber JH: Anesthesia technique, mortality, 
and length of stay after hip fracture surgery. JAMA 2014; 311:2508–17 
4. 
Boddaert J, Cohen-Bittan J, Khiami F, Le Manach Y, Raux M, Beinis JY, Verny M, Riou B: 
Postoperative admission to a ded- icated geriatric unit decreases mortality in elderly patients with hip 
fracture. PLoS One 2014; 9:e83795  
 
Study protocol 
1. Study assumption: To strengthen the comprehensive treatment of perioperative anesthesia is 
possible to improve the prognosis of patients with hip fracture and reduce mortality. 
2. Study design: randomized controlled pilot study. 
3. Subjects: elderly patients with hip fracture on one side and needing surgical treatment. 
4. Inclusion criteria: 
(1) Patients ≥ 75 years old 
(2) Patients with hip fracture purely and surgical treatment is scheduled 
   Exclusion criteria： 
(1) Surgical treatment has been performed after entering hospital; 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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(2) Multiple trauma: multiple fractures; chest, abdomen, pelvis and sacral trauma; severe head 
injury, etc. 
(3) Refuse to sign informed consent; 
(4) Investigator thinks he/she is inappropriate to carry out this study. 
5. Randomized grouping： 
The central random system was used to determine the stratification factor by age (whether > 80 
years old), POSSUM score (whether more than 40 points), whether there was a tracheal intubation 
or the auxiliary ventilation of the laryngeal mask. Randomized grouping (1:1). 
(1). New “guideline” anesthesia strategy team (Group A)  
(2). Current anesthesia strategy team (Group B) 
6. Primary outcome 
Mortality of postoperative of 6 months. 
7. Secondary outcomes 
(1). The intensity of postoperative pain using Visual Analogue Scale (VAS) – collected within two 
days after surgery  
(2). The incidence of postoperative complications – collected post-operation to discharge 
(3). Mortality for postoperative of 30 days and 1 year – collected within 30 days and 1 year after 
surgery 
(4). Length of time after surgery to death 
(5). The level of compliance of new “guideline”(from the ratio of score：total score) – duration of 
hospital stay, an average of 2 weeks 
(6). Length of hospital stay – up to discharge, an average of 2 weeks 
(7). Total cost in hospital and expenditure for anesthesia – length of hospital stay, an average of 2 
weeks 

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(8). Cognitive function with Mini-Mental State Examination (MMSE) – within two days after surgery 
(9). Overall satisfaction of patients -  collected no more than two weeks before discharge 
8. Study withdrawal 
(1) Subject can withdraw from the study at any time without giving any explanation, and will not 
lose the right to medical care in the future; 
(2) The primary orthopedic physician or anesthesiologist believes that the patient's condition is 
not suitable for continuing the study; 
(3) During the study, if two anesthesia management strategies were found significantly different 
in prognosis of patients and could be terminated in advance; 
(4) The ethics committee demands that the study be terminated. 
9. Implementation of anesthesia strategies and data collection 
Three anesthesiologists were assigned to adopt the new "guideline" of the anesthetic strategy, and 
the anesthesia management of group A was carried out. Other anesthesiologists performed the 
management of group B in accordance with their own routine. A research nurse was assigned to 
collect data from preoperative and operative procedures and to complete random grouping. Another 
study nurse (who was blind of grouping condition) was assigned to collect the postoperative data to 
avoid subjective bias and to blind the observer. The data collection table is table 1 below. 
Table1:data collection 
Period 
Variable 
Approach 
Preoperativ
e data 
Age, gender, address, type of fracture, past medical 
history, 
ASA 
grade, 
cognitive 
function(MMSE), 
POSSUM grade, VAS grade 
Medical history, 
MMSE, visit 
During 
operation 
Type of surgery, level of surgeon, type of anesthesia, 
level of anesthetist, Narcotic drugs and dosage, 
hypotension, operation duration, estimated blood loss, 
Medical history, 
anesthesia 
notes, visit 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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transfusion volume 
Postoperati
on 
Compliance degree to the new “guidelines”, length of 
hospital stay, cognitive function(MMSE), VAS grade, 
fee of hospitalization, fee of anesthesia, adverse 
event, mortality in hospital, mortality within 30 days, 
whether withdraw study 
Medical history, 
visit 
In 6 
months 
and 12 
months 
Mortality, living quality 
The telephone 
follow-up 
 
 
 
 
 
 
 
 
 
 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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10. Flow diagram： 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Select the patient according to the inclusion criteria 
Obtain informed consent of patient and family 
Elderly patients with hip fracture 
Randomly grouping according to the anesthetic strategy 
Existing anesthesia strategy group 
"Guidelines" anesthesia strategy group 
Primary outcomes：Mortality in 6 months of postoperative; The incidence of postoperative complications 
Secondary outcomes：The level of compliance of new “guideline” within 30 days and one year following hospital discharge, the length of hospital stay, 
mortality of hospitalization and within 30days after surgery, and total cost in the hospital 
Preoperative data, concomitant 
disease, cognitive function, 
POSSUM score, etc 
Data lock, statistical analysis, writing thesis 

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Note: Total loss of blood, abdominal pollution, malignant tumor, type of operation, and lack of data are 
recorded as 1 point. 
11. Adverse events 
(1) Definition of adverse events and adverse reactions 
 (Adverse Event, AE) It refers to any adverse symptoms, abnormal signs and abnormal test results 
that occur after the intervention, whether or not there is a causal relationship with the intervention. 
Any adverse events, including the subjects offered, by researchers ask or by physical examination, 
laboratory examination, or other examination methods, medical records should be recorded in the 
research, and actively processing, strictly follow-up, till to alleviate or being in a stable condition. 
 (Adverse Drug Reaction, ADR)： The harmful, rather than expected, and causal relationship 
between the use of drugs in the prescribed dose of normal dosage of the drug. 
(2) Records of adverse events 
 
All adverse events must be tracked. The investigator must document the corresponding 
parts of the case report and must record the adverse events in detail. 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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 
Adverse event content: symptom name or sign name or disease diagnosis name or 
laboratory examination of an abnormal indicator. 
 
Start date of adverse event: the first occurrence of AE or AE related symptoms. 
 
End date of adverse event: the date of filling in AE or the symptoms associated with AE. If 
AE still exists, do not fill in the end date. 
 
Assess the severity of adverse events 
a. Mild: symptoms and signs are present, but can be tolerated and generally do not 
require treatment 
b. Moderate: symptoms or signs may cause discomfort, daily activities are limited, and 
appropriate treatment measures may be taken 
c. Severe: no ability to carry out work and daily activities, and should be actively 
treated 
 
 Measures: to stop the related drugs or treatment, to adopt the treatment measures, and to 
take no measures. 
 
The result of adverse events: still exist, improve and have been relieved 
 
Correlation evaluation of adverse events and anesthesia: 
Evaluation criteria of the five levels: 
a. It must be related: the occurrence of adverse events corresponds to a reasonable 
time sequence after anesthesia; 
The production of adverse events is more reasonable than others; 

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The pattern of adverse events is consistent with the adverse reaction patterns 
produced by such anesthesia. 
b. May be related: the occurrence of adverse events is in accordance with the 
reasonable time sequence after anesthesia; 
The occurrence of adverse events is more reasonable than other causes by using 
anesthesia explanation; 
But not for other reasons. 
c. May not be related: the occurrence of adverse events does not accord with the 
reasonable time sequence after anesthesia; 
The occurrence of adverse events may be caused by other causes, but it cannot be 
ruled out by anesthesia; 
d. Irrelevant: adverse events are caused or excluded by other causes; 
e. Cannot be determined: the occurrence of adverse events does not conform to the 
reasonable time sequence after anesthesia; 
But it was impossible to tell whether it was related to anesthesia, or to explain it in 
other ways. 
12. SAE (Serious adverse event) 
(1) Severe adverse event definition (SAE) 
During the clinical trial, the patient needs to be hospitalized, prolonged hospital stay, 
disability, affecting work ability, life or death, and congenital malformation. 
(2) Serious adverse event handling procedures 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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When serious adverse events occur, all measures should be taken to avoid permanent 
damage. From the subjects began the trials to the observation period, any SAE appeared, the 
researchers must inform the principal investigator within 1 day, 5 days phone call or fax to 
inform clinical research center, the ethics committee, and fill in the part of the case report 
about the serious adverse events. 
(3) The contact of serious adverse events is as follows:： 
Table8 Contacts of SAEs 
Center 
Contact people 
Contact information 
The Second Affiliated Hospital and 
Yuying Children’s Hospital of 
Wenzhou Medical University  
Ting Li 
13587876896 
The Second Affiliated Hospital and 
Yuying Children’s Hospital of 
Wenzhou Medical University 
Medical ethics committee 
0577-88002560 
feykjkcy@126.com 
The Second Affiliated Hospital and 
Yuying Children’s Hospital of 
Wenzhou Medical University 
Good Clinical Practice 
Institution Office/ 
Good Clinical 
Practice Institution Archives 
Room 
 
0577-88002664、88002738 
ywlcsy409@163.com 
13.  Quality control and assurance 
(1) Qualification of the researcher 
To participate in this clinical study, the researchers must have the corresponding professional 
technical position in medical institutions and practicing qualification, a testing scheme of the 
required professional knowledge and experience, has rich experience on clinical trials method 
or get this unit experienced researchers in academic guidance, familiar with the associated 
with the clinical trial data and literature that sponsor offered, have the right to control 

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personnel involved in the test, and handle the equipment needed for this test. Before the 
clinical trials, through training, the researchers can fully understand the specific contents of 
clinical trial protocol and indicators. 
(2) Clinical trials supervision 
This clinical study in inspection work completed by the quality controller that assigned by 
hospital clinical research center, to ensure the test record and data is accurate, complete and 
correct; to ensure the test comply with the relevant standard operating procedures, 
guidelines, manuals, the whole process is following the approved protocol and the relevant 
laws and regulations. 
14.  Ethical principles 
(1) The ethical basis 
The clinical trials follow the Helsinki declaration and our country's regulations and regulations 
on clinical trials. 
(2) Ethics committee 
Prior to the test, the test protocol, the prepared informed consent and other information to the 
patient shall be submitted to the ethics committee (IEC) to review. Prior to the 
commencement of the trial, the written approval of the ethics committee and the date shall be 
obtained. Any amendment to the programme shall be subject to the approval of the 
committee except for the amendments to the management. 
(3) Informed consent 
The researchers are responsible for obtaining a written informed consent form from each 
subject. The subject should not be programmed to conduct any experiments prior to the 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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subject's written informed consent. The researchers should identify the patient's autonomy and 
prevent some patients from participating in the study for possible benefits and lead to influence 
on study. These people should not be included in this study. The researchers should also not 
be treated differently from patients who did not participate in the study, and patients should be 
entitled to normal treatment. 
Before obtaining the written informed consent, the researcher must explain to the prospective 
patient and his guardian the purpose, method, potential risks and possible discomfort of the 
study. Researchers should ensure that the participants in the group with plenty of time before 
asking the details of this study, this research has the responsibility to ensure that patients or 
their legal guardian all problems get a satisfactory answer. 
Participants shall sign the two copies of informed consent and dated, researchers should be 
signed at the same time, both save a copy of the test. In the process of the test, the rights and 
interests of patients should be ensured, patients should follow the principle of confidentiality. 
In the course of the study, patients can ask the researchers questions at any time, and the 
researchers have the obligation to introduce the information to the subjects in a timely manner. 
If there is a major adjustment in the research process, the informed consent form shall be 
signed from patients again. 
15. Data recording and management 
(1) Data entry and modification 
According to the original observation records of the subjects, the researchers recorded the 
data in a timely, complete, correct and clearly recorded form in the original medical records. 
Each selected case had to complete the original medical record. The monitoring personnel of 
the clinical research center shall follow the test plan to confirm the completion of the 

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electronic case report and be consistent with the original data. Data administrator work on 
data entry and management. If there are errors or omissions, the researchers should be 
required to correct them in time and modify the retention of electronic tracks. The electronic 
case report should be properly saved and backed up. 
All data is collected and stored in the Second Affiliated Hospital and Yuying Children’s 
Hospital of Wenzhou Medical University research data platform. Data administrators 
designated by the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou 
Medical University are responsible for the data entry and management. The data 
administrator compiled the table of the electronic case report, work on data entry and 
management. The questions that exist in the case report form, data administrators should 
produce question answer sheets, send ask to the researchers, researchers should answer 
and return as soon as possible. Data manger will modify the data according to the responds 
from researchers, then confirm and entry again. Fill in and transfer of case report form. 
(2) Preservation and summary of information Data audit and lock 
All the data in the system questions resolved, "clean" data export to statisticians. Statistical 
audit by the principal investigator and statistician, and the data is locked. After locking the 
data, file will no longer be altered. 
16. File preservation and summary  
(1) Preservation of relevant materials 
Clinical trials and amendment (signed), the ethics committee approval documents, signed 
informed consent form, the original medical records, case report form (already filled out, 
signed, dated) (reserved copy), serious adverse events, etc. Please file away after the study. 
(2) Data preservation 
The case report was completed by the researcher or the authorized person during the trial 
period and reviewed by the quality controller from the clinical research center. After the 
examination of all cases, the researchers will arrange the data entry, inquiry and statistics can 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
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be completed by the clinical research center or statistician arranged by researchers. The 
original medical records were also saved by the clinical research center of the hospital. 
17. Statistical analysis 
(1) Sample size estimation: According to the results from literature review, elderly hip 
fracture had a 12%~23% mortality of 6 months, and the retrospective analysis of 2014 
from our hospital found a mortality of 18.3% of 6 months. So under the existing 
anesthetic strategy, the mortality was 20% (alpha = 0.05, unilateral), and the relationship 
between the 6-month mortality and sample size of the new "guidance" anesthesia 
strategy group was as follows: 
 
 
 
 
 
The italic number needs 1 year to complete case collection; The underline numbers are 
required to complete the case collection in 1-2 years. The numbers on the box are 
required to complete the case collection by multi-center. 
The new "guidelines" anesthesia strategy can decrease the anticipated mortality of 8% to 
12% of 6 months, the required sample size of 257 cases, considering that withdraw or 
lost to follow-up, set the sample size of 300 cases, 1.5 years to complete the data 
collection. 
(2) Analysis dataset 
 
Full analysis set（FAS）：A collection of all cases of random entry and 
anesthesia。 
In the analysis of the main curative effect indexes, the missing value of FAS is 
processed by the method of the current (LOCF), which was observed at the 
previous point of time. 
In the Case of secondary curative effect indexes, general situation and safety 
analysis, the Available Case Analysis principle is adopted to carry out missing value 
processing. 
 
Per Protocol Set(PPS)： Refers to the collection of cases that meet the inclusion 
criteria and complete the treatment according to the protocol, which is the case in 
which the test scheme, compliance and efficacy (at least the primary efficacy) are 
evaluated. 
 
Safety analysist set(SAS)：At least the anesthesia was carried out and the actual 
data were recorded with the safety index。 
(3) Contents of statistical analysis 
Primary statistical analysis： 
 
Distribution of two groups: the total shedding rate of the two groups and the loss of 
shedding rate due to adverse events. 
 
Comparability analysis: comparison of demographic data and other baseline values 
Mortality 
within 6 
months 
10% 
12% 
14% 
16% 
17% 
1−β=0.8 
155 
257 
481 
1137 
4749 
1−β=0.9 
214 
355 
667 
1574 
6577 

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to measure the comparability of the two groups. 
 
Compliance analysis: compare two groups of patients with the new "guideline" 
compliance. 
 
Effectiveness analysis: the main efficacy indexes were analyzed by PP and ITT. 
 
Factors: Age, sex, drug combination, preoperative complications, ASA grade, 
POSSUM grade and anesthesia type on each stage of mortality and postoperative 
complications, using chi-square test or CMH chi-square; to data that conform to the 
normal distribution, using analysis of covariance, otherwise with H test. 
 
Safety analysis: First, according to the requirements of adverse reaction correlation, 
listing table to describe two groups of adverse events and adverse reactions 
(including the number of cases of adverse events; laboratory examination indexes 
before and after the trial; the number of "normal turn abnormal” cases and variation 
rate).The frequency table was used to summarize the comparison between groups 
using the Chi-square test or Fisher exact test. 
(4) Methods of statistical analysis 
 
The measurement data: The normal distribution was checked in the first place, then 
t test, paired t test, variance analysis and covariance analysis was adopted to test 
whether the data was normally distributed. Wilcoxon rank test, matching rank test, H 
test are used for data that do not conform to normal distribution. 
 
The enumeration data: Adjusted Chi-square test, Fisher exact test were adopted for 
enumeration data. The hierarchical data were analyzed by Ridit, CMH. The 
description of quantitative indicators included mean, standard deviation, median, 

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minimum and maximum value. The description of the classification index using 
counts and percentages. All statistical tests were carried out with unilateral test, and 
the P value was less than or equal to 0.05 was deemed to statistically significant. 
(5)  Data management and statistical software 
 
Data management and statistical software 
The integrated information platform of clinical research in our hospital is adopted. The 
statistical software included SAS9.4 and R 3.4.1 programming. 
 
Parameters in statistical analysis 
All the hypotheses were one side with 0.05 alpha. Therefore, it states significantly in 
statistics when p value is lower than 0.05. 
 
 

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Appendix 1 New elderly hip fracture anesthesia strategy  
 
The measurement of anesthesia 
Implementation  Explanation 
Preoperative 
management 
是否48 h 内实施手术 
Surgery within 48 hours? 
 
2 points: <48h，1 point: <72h >48h，
0 point: >72h. 
Complete analgesia (12 hours in 
admission), VAS<4 points 
 
2 points: <12h ，1 point: <24h  
and >12h，0 point :>24h. 
Preoperative transfusion 
Hb<80～90 g/L，Patients with 
ischemic heart disease 
preoperative transfusion 
Hb<100 g/L. 
 
2 points: complete comply，1point: 
partly comply，0 point: not follow 
Uptaking oxygen within 12 hours 
after injury, according to blood 
oxygen status to determine 
whether to continue to absorb 
oxygen after 12 hours. Target of  
SpO2 is 92% ~ 98%. Coexisting 
chronic respiratory disease or 
Ⅱ respiratory failure patients 
should maintain SpO2 in 88% ~ 
92% 
 
2 points: complete comply, 1 point: 
partly comply, 0 point: not follow 
Management 
during 
operation 
Arrange the degree of doctor in 
vice director or above 
 
2 points: complete comply, 0 point: 
not follow 
Regional block technology 
analgesia 
 
2 points: complete comply, 0 point: 
not follow 
Insulation measure 
 
2 points: complete comply, 1 point: 
partly comply, 0 point: not follow 
Temperature monitoring 
 
2 points: complete comply, 0 point: 
not follow 
Arterial Blood Pressure 
 
2 points: complete comply, 0 point: 
not follow 
Preoperative, intraoperative and 
 
2 points: complete comply, 1 point: 

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postoperative 
blood 
volume 
optimization measures 
partly comply, 0 point: not follow 
术后管理 
Maintain Hb no lower than 90 g/L 
 
1 point: partly comply, 0 point: not 
follow 
Oxygen therapy lasts at least 24 
hours, patients with hypoxemia 
continuously inhaling oxygen 
 
2 points: complete comply, 1 point: 
partly comply, 0 point: not follow 
Postoperative analgesia 
 
2 points ：Nerve block analgesic 
technique, 
1point
：
Epidural 
analgesia, 0 point：Only vein or oral 
or no analgesia 
Note: 2 points: completely comply with the specified implementation as required (the desired index), 1 
point: partly compliance (partly implemented, lack of time or (take measures not exceeding the expectation 
index), 0 point: did not comply with the corresponding measures (no measurement implemented). 
 
 
 
 
 
 
 

Efficacy of Perioperative Anesthesia care bundle on Prognosis in elderly undergoing Hip Fracture Surgery: a single-center randomized controlled trial 
                                                                 Version：1.0 
 
Investigator declaration 
I hereby sign that I have read this project and agree to the content, and will strictly follow this scheme, 
GCP and relevant national laws and regulations. I will discuss the study and relevant information with 
researchers I am responsible for to ensure that they are fully aware of this research medicine and how to 
conduct this clinical trial. 
I will ensure that the subjects can receive proper treatment during the event of adverse events, ensure 
that the subjects take appropriate treatment measures and timely report the occurrence of serious adverse 
events. 
 
Primary investigator: Ting Li 
Primary investigator（signature）:            Date: