Effects of Paravertebral Block on Postoperative Analgesia in Children Undergoing Lateral Incision Cardiac Surgery With Cardiopulmonary Bypass: a Randomized Controlled Trial
Phase: NA
Conditions: Postoperative Pain
Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital

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Effects of paravertebral block on postoperative analgesia in 
children undergoing lateral incision cardiac surgery with 
cardiopulmonary bypass: a randomized controlled trial 
 
 
Research Plan  
 
Project source: The Top-level Hospital Clinical Research Project by Chinese Academy of 
Medical Sciences (2023-GSP-QN-7) 
Principal Investigator: Guo Jingfei 
Sponsor (if applicable): Not involved 
Statistical unit (if applicable): Not involved 
 
 
 
 
2024-02-26 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Abstract  
Research Name 
Effects of paravertebral block on postoperative analgesia in 
children undergoing lateral incision cardiac surgery with 
cardiopulmonary bypass: a randomized controlled trial 
（PVB research） 
Research Goal 
This study aims to determine whether postoperative PVB has better 
postoperative analgesic effect, lower complication rate and quicker 
recovery process compared to local infiltration anesthesia for 
children 
undergoing 
side-incision 
cardiac 
surgery 
with 
cardiopulmonary bypass.  
Research Design 
Single-center，randomized， controlled，double-blinded  
Study population 
Children aged 6-14 years who undergo side-incision atrial septal 
defect repair and/or ventricular septal defect repair surgery with 
cardiopulmonary bypass 
Study intervention 
After surgery, patients in the experimental group undergo 
paravertebral block using drug A, and local infiltration anesthesia 
using drug B. For the experimental group, drug A is 3mg/kg of 
0.375% ropivacaine and drug B is normal saline solution of the same 
volume. After surgery, patients in the control group undergo 
paravertebral block using drug A, and local infiltration anesthesia 
using drug B. For the control group, drug B is 3mg/kg of 0.375% 
ropivacaine, and drug A is normal saline solution of the same 
volume. 
Inclusion criteria 
(1) Children aged 6-14 years old; 
(2) Children who have atrial septal defect or ventricular septal defect 
scheduled for lateral incision cardiac surgery with cardiopulmonary 
bypass; 
(3) Inform consent signed by the parent or legal guardian. 
Exclusion criteria 
(1) Patients who were intubated, on mechanical circulatory support, 
or with intravenous inotropes before surgery; 
(2) Emergency surgery or redo cardiac surgery; 
(3) Body weight more than 50 kg; 
(4) Diagnosed as severe pulmonary hypertension; 
(5) Left ventricular ejection fraction less than 45% in most recent 
echocardiography before surgery; 
(6) Allergic to ropivacaine or other regular anesthetics, analgesics or 
other medications regularly used in the study; 
(7) Preoperative platelet counts less than 100*109/L, coagulopathy 

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or bleeding tendency ; 
(8) Preoperatively using antiplatelets or anticoagulants; 
(9) Diagnosed with scoliosis or other contraindications for PVB. 
Primary outcome 
Total opioid consumption within 24 hours after surgery (ug/kg) 
Secondary outcome
(1) FPS-R scores at 6 hours, 12 hours, 18 hours, and 24 hours after 
surgery 
(2) The rate of opioid treatment for remedial analgesia between 
groups.  
(3) The first time of FPS-R≥4 postoperatively. (recorded by 
bedside nurse) 
(4) Length of postoperative mechanical ventilation, length of ICU 
stay and hospital stay. 
(5) The rate of postoperative nausea and vomiting (PONV) 24 
hours after surgery 
(6) The incidence of respiratory depression in the two groups  
Study period 
2024.3.11-2024.12.31 
Sample size 
100（50 cases each for experimental group and control group） 
 
1. Research Background 
Postoperative pain after cardiac surgery is severe, and adequate postoperative analgesia 
is crucial for quick recovery for cardiac surgery patients. The traditional postoperative 
analgesia model for cardiac surgery is mainly based on opioids. However, the use of 
large doses of opioids can lead to delayed postoperative recovery. In recent years, the 
promotion and application of accelerated recovery surgery theory have led to an overall 
improvement in medical quality (1, 2). The theory of Enhanced Recovery After Surgery 
emphasizes postoperative multimodal analgesia to reduce opioid use. Postoperative 
intravenous analgesia combined with regional anesthesia is one of them, such as 
combined epidural anesthesia, spinal anesthesia, sacral anesthesia, thoracic 
paravertebral nerve block (PVB), etc. 
However, there are risks associated with epidural anesthesia, spinal anesthesia, or sacral 
analgesia after cardiac surgery. Cardiac surgery requires systemic blood heparinization, 
which despite neutralization with protamine, can leave patients more susceptible to 
serious complications such as epidural hematoma than with other types of surgery. 
Therefore, new regional blocks such as PVB have gradually emerged in recent years. 
Compared with epidural block, PVB is easier to operate and can avoid complications 

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such as epidural abscess, hematoma, general spinal anesthesia, spinal cord, or spinal 
nerve injury. 
An RCT of patients undergoing central sternotomy for cardiac surgery showed that 
patients who underwent bilateral PVB had the same postoperative pain scores, shorter 
postoperative ICU length of stay, less nausea and vomiting, and less urinary retention 
compared to those who underwent epidural blockade (3). Another RCT showed that 
during side-incision cardiac surgery, patients who underwent unilateral PVB had no 
significant difference in postoperative pain scores and had lower rates of nerve block 
failure and nausea compared with patients who underwent epidural blockade. The 
incidence of complications such as vomiting, urinary retention, and hypotension is also 
lower (4). However, there are currently no RCT studies in side-incision cardiac surgery 
comparing postoperative paravertebral blockade with intravenous analgesia 
alone/incisional local anesthetic infiltration. In thoracic surgery, similar studies have been 
conducted with positive results (5, 6). An RCT study of PVB for lung surgery showed (6) 
that compared with simple intravenous analgesia, the PVB group had lower 
postoperative pain scores and less morphine consumption; while local infiltration 
analgesia had no significant difference compared with intravenous analgesia alone (5). 
At present, the number of minimally invasive cardiac surgeries with side incisions is 
gradually increasing. In order to cooperate with the development of surgery and 
enhanced recovery process , it is crucial to develop postoperative PVB analgesia 
technology. This study aims to determine whether postoperative PVB has better 
postoperative analgesic effect, lower complication rate and faster recovery process 
compared with simple local infiltration anesthesia for children undergoing side-incision 
cardiac surgery with cardiopulmonary bypass.  
 
2. Research purpose 
This study aims to determine whether postoperative PVB has better postoperative 
analgesic effect, lower complication rate and faster recovery process compared with 
simple local infiltration anesthesia for children undergoing side-incision 
cardiopulmonary bypass cardiac surgery.  
 
3. Research Method 
3.1 Overview of experimental design 
This study is a single-center, randomized, double-blind trial that aims to determine 
whether post-operative PVB provides better postoperative analgesia, lower incidence of 
complications, and faster recovery process compared with simple local infiltration 
anesthesia for children undergoing side-incision cardiac surgery with cardiopulmonary 
bypass. This trial will be registered on ClinicalTrials.gov before starting. A detailed 
statistical analysis plan will be developed before starting data analysis. Results reporting 

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will strictly follow CONSORT guidelines. 
3.2 Subject selection 
3.2.1 Inclusion criteria 
(1) Children aged 6-14 years old; 
(2) Children who have atrial septal defect or ventricular septal defect scheduled for 
lateral incision cardiac surgery with cardiopulmonary bypass; 
(3) Inform consent signed by the parent or legal guardian. 
3.2.2 Exclusion criteria 
(1) Patients who were intubated, on mechanical circulatory support, or with intravenous 
inotropes before surgery; 
(2) Emergency surgery or redo cardiac surgery; 
(3) Body weight more than 50 kg; 
(4) Diagnosed as severe pulmonary hypertension; 
(5) Left ventricular ejection fraction less than 45% in most recent echocardiography 
before surgery; 
(6) Allergic to ropivacaine or other regular anesthetics, analgesics or other medications 
regularly used in the study; 
(7) Preoperative platelet counts less than 100*109/L, coagulopathy or bleeding 
tendency ; 
(8) Preoperatively using antiplatelets or anticoagulants; 
(9) Diagnosed with scoliosis or other contraindications for PVB. 
3.2.3 Subject withdrawal criteria and procedures 
The researcher may ask the subject to withdraw from the trial at any time during the 
research process. At the same time, the subject may also spontaneously request to 
withdraw from the trial at any time. The reasons for withdrawal include but are not 
limited to: 1) the subject revokes informed consent; 2) the subject is lost to follow-up; 3) 
the researcher fully assesses the subject from a safety perspective and deems the 
subject not suitable to continue the trial. 
Withdrawal of informed consent means that after obtaining relevant information about 
the subject's trial, the subject refuses to have further contact with the researcher or his 
authorized person. The subject should try to inform the researcher in writing that he or 
she is withdrawing his or her consent for future follow-up. In case of informed consent, 
the researcher should specify the specific reasons for the subject's withdrawal of 
informed consent in the case report form (CRF). Subjects may withdraw from the trial at 
any time at their own request, or may be asked to withdraw from the trial at any time by 
the investigator, the Data Safety Monitoring Board or the Clinical Events Committee for 
safety or behavioral reasons, or if the subject is unable to comply with specific trial 
procedures. In this case, subjects should be encouraged to stay in contact with the 
investigators and continue to be followed up by telephone and other means during the 

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remainder of the trial to better assess the safety indicators of the trial. If a subject 
withdraws from the trial and withdraws informed consent for future disclosures, no 
further assessments should be conducted and additional data should not be collected, 
but the investigator may retain and continue to use any data collected before the 
withdrawal of informed consent. 
Loss to follow-up refers to the inability to contact the subject at the end of the trial. No 
subject should be considered lost to follow-up until the trial is completed. If the subject 
does not see the doctor as planned, every effort should be made to contact the subject, 
which can be by phone, email, text message, social media, or if necessary, by letter 
and/or registered call if necessary. If the subject has died, the date and cause of death 
should be obtained. If follow-up of this information is not possible, the last known date 
of survival determined should be reported and recorded on the subject's CRF form. 
3.3 Intervention or product introduction 
Patients in the experimental group received paravertebral block with 3 mg/kg of 0.375% 
ropivacaine. Paravertebral block is a commonly used regional block technology. 
Compared with traditional epidural anesthesia, it has the advantages of relatively stable 
circulation, lower requirements for coagulation function, and lower complication rate. 
Paravertebral block can be used for all surgeries from the chest to the pubic symphysis. 
This study used the thoracic paravertebral block. Specific implementation methods of 
paravertebral block include blind exploration method, nerve stimulator guidance 
method, ultrasound guidance method, etc. This study adopts ultrasound-guided 
paravertebral block technology, which enables accurate positioning and reduce the 
occurrence of complications such as anesthetic injection into blood vessels and 
pneumothorax. 
3.4 Research process 
3.4.1 Research flow chart 
3.4.2 Research implementation (method, content, steps, etc.) 
1) Before surgery: 
The investigator will conduct a pre-screening process to assess whether potential 
subjects are suitable for inclusion in this study. After pre-screening, the investigator will 
conduct a screening process to assess whether the subjects meet the inclusion criteria. 
Before the process of screening subjects, researchers need to obtain informed consent. 
Our assessment mainly collects the following information: 
A. Informed consent: When contacting the subject for the first time, the researcher 
should explain the entire process of the trial to the subject or their legal representative 
and obtain their informed consent; 
B. Demographic information: gender, date of birth, race, height and weight; 
C. Medical history: Medical history relevant to this study, including primary diagnosis, 
NYHA classification, diabetes, hypertension, hyperlipidemia, infective endocarditis, 

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COPD, peripheral vascular disease, cerebrovascular disease, previous cardiac surgery 
history, smoking history, allergy history and current medications (beta blockers, ACE 
inhibitors, ARBs, statins，diuretics); 
D. Basic vital signs: body temperature, heart rate, blood pressure, oxygen saturation 
E. Related examinations: echocardiography, routine blood tests, liver and kidney 
function tests, and coagulation function tests 
2) Intraoperative: 
Implementation of intervention: After the operation, patients in the experimental group 
and the control group were treated with drug A for paravertebral block, and drug B for 
local infiltration block through the incision. Paravertebral block is performed under 
ultrasound guidance, and right T4 paravertebral nerve block is performed. It is 
recommended to use the needle insertion method in the sagittal plane. Use 0.375% 
ropivacaine at a dosage of 3 mg/kg. The rest of the intraoperative anesthesia protocol is 
the same as the clinical routine. 
Intraoperative anesthesia management: Give anesthetic drugs and perform 
intraoperative management according to the routine of the anesthesia center. 
Intraoperative record information: basic intraoperative information such as type of 
operation, operation time, etc. 
3) After surgery: 
Routine postoperative analgesia plan: Children are not routinely given analgesic pumps 
and other analgesic measures after surgery. The ICU bedside nurse observes the 
patient's pain condition at any time. When the patient shows any signs of discomfort or 
pain (such as crying, painful expression, body twisting, etc.), the ICU bedside nurse 
conducts a FPS-R pain score on the child. If the FPS-R score is ≥4, sufentanil 0.05 
μg/kg/h will be continuously pumped intravenously. If 0＜FPS-R score＜4，than Non-
opioid analgesics will be given. 
Postoperative follow-up information: record the total amount of opioids taken by the 
patient within 24 hours after surgery; FPS-R scores at 6 hours, 12 hours, 18 hours, and 
24 hours after surgery; the time when the first FPS-R ≥ 4 points after surgery; incidence 
of nausea and vomiting 24 hours after surgery, the incidence of serious complications 
such as respiratory depression, postoperative mechanical ventilation time, ICU stay time, 
postoperative hospital stay. 
3.5 Criteria for suspension/termination of studies 
The researcher has the right to suspend/terminate this study at any time during the trial. 
The reasons for suspension/termination include but are not limited to, 1) The incidence 
and severity of adverse events reported in this study or other similar studies indicate 
that continuing this trial will be harmful to the subjects. The subjects pose potential 
health threats; 2) The subjects are not satisfied with the enrollment. 
The researcher has the right to replace any research center at any time during the trial. 

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The reasons for suspending/terminating the research center's continued participation in 
this study include, but are not limited to, 1) extremely slow recruitment of subjects and 
insufficient recruitment; 2) poor trial compliance; 3) inaccurate or incomplete data 
recording; 4) non-compliance with the GCP guidelines of the International Conference 
on Harmonization (ICH). 
3.6 Endpoint evaluation 
3.6.1 Effectiveness evaluation 
1) Primary endpoint: total opioid consumption within 24 hours after surgery (ug/kg) 
2) Secondary endpoints: other postoperative analgesic indicators. 
A. FPS-R scores at 6 hours, 12 hours, 18 hours, and 24 hours after surgery. (See 
attachment 1)  
B. Rates of postoperative opioid rescue analgesia use in both groups. 
C. Time to first postoperative FPS-R ≥ 4 points (recorded by bedside nurse) 
D. Postoperative mechanical ventilation time, ICU stay time, and postoperative 
hospitalization time 
3.6.2 Safety evaluation 
The incidence of vomiting in two groups of children within 24 hours after surgery 
The incidence of serious complications including respiratory depression in the two 
groups of children 
3.7 Randomization method and blinding method 
3.7.1 Blinding 
For children who signed informed consent and screened into the group, their baseline 
information is recorded, and randomization is conducted after entering the operating 
room. The children are randomly grouped using the block randomization method. After 
the random numbers are generated by the computer, all the random numbers are 
coded and sealed into opaque envelopes. The code, that is, the selection number, was 
written on the outside of the envelope, and the random number was placed inside the 
envelope. The children were randomly divided into the experimental group (PVB group) 
and the control group (local infiltration group). This study is blinded to the 
intraoperative anesthesiologists, patients, data collectors and analysts, and study result 
evaluators. Before surgery, a pharmacist who is not involved in the follow-up process 
opens the envelope and prepares medications based on the grouping results. The 
pharmacist prepares two medications, A and B for each patient. Drug A for patients in 
the test group is 3 mg/kg of 0.375% ropivacaine, while for patients in the control group, 
drug A is the same volume of normal saline. Drug B for patients in the control group is 
0.375% ropivacaine at 3 mg/kg, and drug B for patients in the test group is the same 
volume of normal saline. The anesthesiologists all use drug A to perform paravertebral 
block on the patients, and drug B to perform local infiltration on the patients. The 
intraoperative anesthesia management plans of the two groups of patients are exactly 

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the same, so they are blinded. All patients undergo paravertebral block and local 
infiltration twice, so they are blinded. The anesthesiologists who collect intraoperative 
and postoperative data do not know the patient grouping information, so they are 
blinded. The ICU nurse who evaluates the patient's postoperative pain and adds 
analgesics does not know the patient's group information and is therefore blinded. 
Principle of unblinding: If a subject has an adverse event that is suspected to be related 
to the trial operation and cannot be alleviated by standard clinical treatment methods, 
for the safety of the subject, emergency unblinding should be carried out. Before the 
trial begins, each research center will be educated and instructed on the blinding 
process. If unblinding is necessary, the principal investigator needs to contact the drug 
dispenser to obtain the trial drug distribution information of the subject, and this 
unblinding process can only occur when the safety of the subject is threatened. If 
feasible, before unblinding, it is best for the principal investigator to communicate with 
members of the trial team to reconfirm the need for urgent unblinding. Once 
emergency unblinding is carried out, the reason for unblinding must be recorded in 
detail in the CRF, and the subject is no longer given the trial drug, but the subject can 
remain in the trial cohort until follow-up is completed. 
3.7.2 Randomization method 
This study is blinded to the anesthesiologists who performed intraoperative 
management, patients, and postoperative evaluators. The intraoperative anesthesia 
management plans of the two groups of patients are exactly the same: drug A is used 
for paravertebral block and drug B is used for local infiltration anesthesia of the surgical 
incision. Patients and their families are blinded (both the experimental group and the 
control group received paravertebral block of the back and local infiltration anesthesia 
of the wound so that family members and other clinicians ostensibly would not know 
about the children's grouping). The evaluators are blinded (the person conducting the 
postoperative pain score does not know the children's grouping and the third-party 
independent evaluation including the central laboratory does not know the children's 
grouping either). 
4. Statistical considerations 
4.1 Sample size estimation 
Sample size calculation is based on the primary outcome, total opioid consumption 
within 24 hours after surgery. Referring to the preliminary test results, the average total 
opioid consumption within 24 hours after surgery in the traditional low-dose opioid 
anesthesia group was 850± 180 μg/kg MSE. According to previously published 
literature (12，13) and the experience of clinical experts, it is assumed that in the PVB 
group, total opioid consumption within 24 hours after surgery was reduced by an 
average of 30%，255 μg/kg MSE. At the same time, the combined standard deviation 
was conservatively estimated to be 425 μg/kg MSE. When the significance level of the 

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statistical test was taken to be one-sided 0.025, the power level was taken to be 80%. 
hour. According to statistical principles, 45 children need to be enrolled in each group, 
and the total number of cases in the two groups is 90. Sample size calculation was 
performed using the PASS software. Taking into account the maximum possible 
dropout rate of 10% in the study, this trial will eventually enroll 100 children, 50 children 
in each group. 
4.2 Statistical Analysis Plan 
This trial will be analyzed according to the intention-to-treat principle, and any subject 
who completes randomization will be followed up until the end of the trial (unless the 
subject withdraws informed consent). This study uses SPSS data analysis software for 
analysis. Quantitative data will be expressed as mean ± standard deviation or median 
(interquartile range) depending on whether it conforms to the normal distribution; 
enumeration data will be expressed as frequency (percentage). Group patients 
according to intervention measures, compare differences between groups and express 
them as absolute standard deviations. Comparisons between groups are performed 
using the two independent sample t-tests for normally distributed measurement data, 
comparisons between groups are performed using the rank sum test for skewed 
measurement data, and comparisons between groups are performed using the χ2 test 
for enumeration data. All tests are two-sided, and P<0.05 means the difference is 
statistically significant. 
5. Data management 
5.1 Data collection and CRFs 
The data collection of this study is based on paper CRF forms, and all data and its 
collection process will be completed under the supervision of the trial management 
center. After the trial is completed, all data and CRF forms will be provided to the 
principal investigator for long-term storage. 
5.2 Saving of test files 
The trial documents will be archived securely and confidentially so that they can be 
reviewed for compliance at any time. The relevant medical documents of the subjects 
will also be archived in accordance with regulations and saved for the maximum period 
allowed by the medical institution. If the archive changes, the researcher and the study 
center need to report to the ethics committee and shall not destroy trial-related 
documents without the approval of the ethics committee. 
5.3 Data quality 
The ethics committee and clinical trial institutions will regularly monitor the quality of 
the data, and the researchers will allow the monitors to obtain any trial-related data at 
any time. 
6. Confidentiality principle 
This study will take the following measures to strictly protect the privacy and personal 

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information of each subject: (1) Confidentiality measures and information security 
systems for sample providers have been established; (2) Samples and data are stored 
securely, and all samples and data in the library are /or set access rights for data; (3) 
When samples or prepared research samples are transferred to other researchers or 
institutions, all collected samples shall be de-identified (coding management and 
deletion of all identification information); (4) Data resulting from the research may be 
published or published publicly, but name or personally identifiable information will not 
be released. 
7. Quality control of research 
7.1 Data Security Monitoring Board 
The independent Data Safety Monitoring Board (DSMB) will monitor the entire process 
of this trial. All serious adverse events must be reported to DSMB. If serious clinical 
safety risks arise, DSMB will give specific opinions to the principal investigator and 
clinical trial institution. Including 1) continue the trial; 2) continue the trial after 
adjustment; 3) terminate the trial. 
7.2 Researchers and training 
Before the trial begins, researchers who can maximize the safety and compliance of the 
subjects will be selected based on their abilities and experience. In addition, only trained 
researchers who are familiar with the protocol can participate in this study, and training 
records will be stored in files. 
7.3 Research monitoring 
After the study begins, regular monitoring will be conducted to evaluate the progress of 
the study, adequacy of records, and compliance with the study protocol, and 
corresponding monitoring records will be provided to the investigators. In addition to 
regular on-site monitoring, remote monitoring will also be conducted to ensure timely 
submission of data. Monitors will maintain ongoing communication with researchers 
through written correspondence, telephone calls, or online conversations. 
8. Ethical principles 
8.1 Ethical approval 
Research can only be implemented after approval by the Ethics Committee. During the 
research process, the research plan and operating procedures must be strictly followed. 
At the same time, modifications to the research plan and informed consent must be 
reviewed and approved by the Ethics Committee before execution. 
8.2 Informed consent 
Before each research subject is selected for this study, the researcher must provide him 
or his legal representative with a complete, comprehensive, easy-to-understand 
content and explanation of the informed consent form approved by the ethics 
committee in writing, and give it to the research subject or their legal representatives 
who will be given sufficient time to consider whether to participate in this study. The 

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research can only be entered after the research subjects or their legal representatives 
sign the informed consent form. During the study, if new safety information causes 
significant changes in the risk/benefit evaluation, all updated new information should be 
provided to the subjects or their guardians and a new informed consent form should be 
signed. 
8.3 Risk-benefit analysis 
This study will not bring risks to subjects beyond routine diagnosis and treatment. Most 
of the clinical outcomes in this study are determined based on questionnaires and 
routine clinical examination results, and only a small amount of additional blood is 
drawn from the subjects for the detection of inflammation and pain-related factors. 
Participants will not receive direct benefit from participating in this study, but if 
participants are assigned to the intervention group, the intervention may reduce the 
occurrence of postoperative pain, but it may also have no effect. At the same time, the 
follow-up personnel during the follow-up period will provide you with treatment and 
healthcare-related suggestions based on the subject's condition. Subject participation 
may help us identify safer or more effective diagnosis and treatment methods and 
expand new scientific knowledge. 
8.4 Conflict of interest 
not involving 
8.5 Subject protection measures 
Participants are not required to pay any research-related costs for participating in the 
study. Subjects’ de-identified information and de-identified biological samples may be 
used to create products or provide health-promoting services. If these situations occur, 
we will not inform the subjects, pay the subjects, or provide any compensation to the 
subjects or their families. Most uses of biological samples and biological information do 
not result in a commercial product or benefit to anyone. No remuneration or 
compensation will be provided to the subjects in this study. 
When the subject's health condition is harmed while participating in this study, the 
researchers are informed, and we will take necessary measures in a timely manner and 
determine compensation or compensation liability in accordance with the relevant laws 
and regulations of our country. 
9. Pre-assessment of project risks and risk treatment plan 
Investigator reports SAE to the ethics committee 
If an SAE occurs during the study, the investigator should immediately report all serious 
adverse events to the sponsor in writing (within 24 hours after the investigator learns of 
the event), and then provide a detailed and written follow-up report in a timely manner. 
At the same time, researchers must fill in the "Serious Adverse Event Report Form" to 
record the time of SAE occurrence, symptom description, severity, duration, measures 
taken, outcomes, basis for correlation assessment, and possible explanations for SAE, 

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etc. If the researcher is unable to learn of a serious adverse event in time (for example, 
the subject was first treated in another hospital), he or she should report and record the 
time when the serious adverse event was first learned within 24 hours after becoming 
informed. 
Typically, this information should include a detailed description of the serious adverse 
event to allow for a complete medical evaluation of the event and an initial independent 
determination of the possible cause. In addition, information must be provided on other 
possible causes, such as concomitant medications and concomitant diseases. In the 
event of death of a subject, the autopsy report must be submitted as soon as possible if 
available. 
Researchers report SUSAR to ethics committee 
Researchers should promptly sign and read the relevant safety information of clinical 
trials such as Suspicious and Unexpected Serious Adverse Reactions (SUSAR) provided 
by the sponsor, consider the subject's treatment, whether to make corresponding 
adjustments, and communicate with the subject as soon as possible if necessary , and 
the SUSAR provided by the sponsor should be reported to the ethics committee. 
9.1 Adverse events (AEs) 
All AEs need to be reported regardless of whether they occur related to trial procedures 
or drugs. At the same time, researchers need to follow up closely to determine whether 
they are related to trial procedures or drugs, patients‘ clinical outcomes, and whether 
they can be upgraded to serious adverse events (SAEs). This follow-up process needs to 
continue until the AEs and their related symptoms are reasonably controlled to a stable 
level. 
9.2 Adverse event reporting interval 
For SAEs, if they occur within 90 days from the time the subject signs informed consent 
to the trial operation intervention, they must be reported to the clinical trial institution; if 
they are not within this interval, but the researcher determines that its occurrence may 
be related to trials, it also needs to be reported to clinical trial institutions. At the same 
time, both AEs and SAEs need to be recorded in detail in the CRF. 
9.3 Definition of SAEs 
SAEs are defined as adverse events with unexpected clinical outcomes during clinical 
trials, including death, serious life-threatening events, need for readmission, prolonged 
hospitalization, permanent disability or disability, and teratogenic mutations. 
SAEs in this trial included IABP, ECMO, reintubation, tracheotomy, severe respiratory 
depression, reoperation, perioperative myocardial injury, and stroke. 
9.4 Definition of AEs 
AEs are unanticipated clinical events that occur in subjects using an investigational drug 
or device during a clinical trial, and the event does not need to be related to the 
intervention. 

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9.5 Severity and relevance assessment 
This study will use mild, moderate, and severe to classify the severity of AEs. Mild means 
that the AEs do not affect the subjects' daily life, moderate means that the AEs affect the 
subjects' daily lives to a certain extent, and severe means that the AEs significantly affect 
the subjects' daily lives. In addition, the correlation between AEs and the intervention is 
assessed and recorded in CRFs. 
9.6 Reporting Adverse Events 
All SAEs and serious AEs need to be reported to the clinical trial institution within 
24 days of occurrence. Non-serious AEs need to be recorded in detail in CRFs. 
 
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men. Pain. 2019;160(8):1691-2. 
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Choi JC, Park YH, Park SK, Lee JS, Kim J, Choi JI, et al. Testosterone effects on pain 
and brain activation patterns. Acta Anaesthesiol Scand. 2017;61(6):668-75. 
9. 
Boll S, Almeida de Minas AC, Raftogianni A, Herpertz SC, Grinevich V. Oxytocin 

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and Pain Perception: From Animal Models to Human Research. Neuroscience. 
2018;387:149-61. 
10. Choi HY, Lee CH. Can Beta-Endorphin Be Used as a Biomarker for Chronic Low 
Back Pain? A Meta-analysis of Randomized Controlled Trials. Pain medicine (Malden, 
Mass). 2019;20(1):28-36. 
11. Karuppiah N, Pehora C, Haller C, Taylor K. Surgical Closure of Atrial Septal Defects 
in Young Children-A Review of Anesthesia Care in Sternotomy and Thoracotomy 
Approaches. J Cardiothorac Vasc Anesth. 2021;35(1):123-7. 
12. Feng, J., et al. (2023). "Effects of Thoracic Paravertebral Block on Postoperative 
Analgesia in Infants and Small Children undergoing Ultra-Fast Track Cardiac Anesthesia: 
A Randomized Controlled Trial." J Cardiothorac Vasc Anesth 37(4): 539-546. 
13．Sahajanandan, R., et al. (2021). "Efficacy of paravertebral block in "Fast-tracking" 
pediatric cardiac surgery - Experiences from a tertiary care center." Ann Card Anaesth 
24(1): 24-29. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Informed Consent 
We invite your child to participate in a study initiated/funded by Fuwai Hospital, Chinese 
Academy of Medical Sciences on " Effects of paravertebral block on postoperative analgesia 
in children undergoing lateral incision cardiac surgery with cardiopulmonary bypass: a 
randomized controlled trial". This study has been approved by the Ethics Committee of Fuwai 
Hospital, Chinese Academy of Medical Sciences (tel: 010-88396281, 010-88396282). Please 
read the instructions carefully to understand your rights and obligations in the research, and 
to understand the nature and risks of the research. Participation in this study is completely 
voluntary, and whether you participate in this study or not will not affect your treatment and 
other legitimate rights and interests during your stay in the hospital. While the researcher 
explains and discusses the informed consent form with you, you can always ask questions and 
have the researcher explain anything you don't understand. You have plenty of time to discuss 
your decision with family, friends, and your doctor. 
If your child is currently participating in another clinical study, please inform the 
researchers. 
The project leader of this study is Guo Jingfei, attending physician of anesthesiology. 
The source of funding for this project is: clinical research funding for the top-level medical 
centers.  
 
1. Why is this study conducted? 
Postoperative analgesia regimen after cardiac surgery is critical to a patient's rapid 
recovery. Traditional opioid-based postoperative analgesia may lead to increased 
postoperative complications and prolonged recovery time. Currently, multimodal analgesia 
is advocated for postoperative analgesia, and nerve block, including paravertebral block, is 
an important part of multimodal analgesia after cardiac surgery. Currently, for lateral-
incision cardiac surgery with cardiopulmonary bypass, there are no randomized controlled 
studies to clarify the postoperative analgesic effect, safety, and impact of paravertebral 
block on rapid postoperative recovery. This double-blinded randomized controlled trial 
aims to study whether pediatric patients who underwent paravertebral block have less 
postoperative pain, fewer complications and faster recovery process compared to patients 
who underwent local infiltration anesthesia.  
 
2. Why are your children invited to participate in this study? 
The inclusion and exclusion criteria for this study are: 
Inclusion Criteria: 
(1) Children aged 6-14 years old; 
(2) Children who have atrial septal defect or ventricular septal defect scheduled for lateral 
incision cardiac surgery with cardiopulmonary bypass; 
(3) Inform consent signed by the parent or legal guardian. 
Exclusion Criteria 
(1) Patients who were intubated, on mechanical circulatory support, or with intravenous 
inotropes before surgery; 
(2) Emergency surgery or redo cardiac surgery; 

17 
 
(3) Body weight more than 50 kg; 
(4) Diagnosed as severe pulmonary hypertension; 
(5) Left ventricular ejection fraction less than 45% in most recent echocardiography before 
surgery; 
(6) Allergic to ropivacaine or other regular anesthetics, analgesics or other medications 
regularly used in the study; 
(7) Preoperative platelet counts less than 100*109/L, coagulopathy or bleeding tendency ; 
(8) Preoperatively using antiplatelets or anticoagulants; 
(9) Diagnosed with scoliosis or other contraindications for PVB. 
 
3. The process and methods of this research 
The intervention of this study is paravertebral block, a commonly used perioperative 
analgesia method that is quite safe when administered under ultrasound guidance. 
This study is a randomized controlled clinical trial. After you agree that your child will 
participate in this study, your child will be randomly assigned to the intervention group or 
the control group. The probability of entering the two groups is equal. The intervention we 
take in the two groups are: patients in the experimental group will have paravertebral block 
using 3 mg/kg of 0.375% ropivacaine after the operation, and patients in the control group 
will have paravertebral block using the same volume of normal saline to simulate the 
experimental group after the operation. Patients in the control group will be treated with 3 
mg/kg of 0.375% ropivacaine for local infiltration anesthesia after the operation, and patients 
in the experimental group will be treated with the same volume of normal saline to simulate 
the control group after the operation. 
Throughout the study, your child's demographics, medical history, basic vital signs, test 
results, information about adverse events, pain scores and opioid dosage, the length of 
postoperative ICU stay and hospital stay will be recorded. We also need to collect blood 
samples from your child at certain time points for testing of relevant indicators. 
 
4. Duration of the study and number of participants 
This study is a single-center clinical study and plans to recruit 100 research participants 
at Fuwai Hospital, Chinese Academy of Medical Sciences. The planned duration of this study 
is from March 2024 to December 2024, and your child is expected to participate until 
discharge. 
 
5. What do you need to do to participate in this study? 
Before enrolling in the study, the doctors will ask and record your child's medical 
history, comorbid diseases and treatment, and conduct physical examination to determine 
whether your child meets the research criteria. Then the researchers will obtain your 
informed consent and sign an informed consent form. Once your child is included in the 
study, he/she will undergo preoperative, intraoperative and postoperative interventions 
guided by researchers and doctors. At the same time, you need to provide complete 
medical history information so that our team members can fully judge your risk and benefits 
at any time during the study, and decide whether your child should continue participating in 
the study. 

18 
 
We will record the dosage of analgesic drugs within 24 hours after the operation, and 
visit your child at 6 hours, 12 hours, 18 hours, and 24 hours after the operation to record 
pain and complications during the postoperative period. This would require the child's 
cooperation. We will draw a small amount of blood samples for testing at three time points: 
before the operation, 6 hours after the operation, and 24 hours after the operation (the 
total volume of blood collected shall not exceed 20ml), and your child's cooperation is 
required. 
 
6. What are the risks and adverse events for study participants in this study? 
Some side effects may occur during the trial. Complications of paravertebral nerve 
block are not common, especially when conducted under the guidance of ultrasound. Most 
complications are transient and do not cause serious damage. However, as a nerve block 
method, it does have certain risks, such as puncture-caused nerve injury, hypotension after 
the nerve block, localized hematoma, infection, etc. 
 
7. Are there any direct benefits from participating in this study? 
Your child may not benefit directly from participating in this study. Your child's 
participation may lead to improvements in medical care, the development of safer or more 
effective treatments, and new scientific knowledge. 
 
8. If I do not participate in this study, are there any other treatment options? 
You can choose not to participate in this study, which will not affect your child’s regular 
treatment. At present, the conventional treatment method for postoperative pain after 
cardiac surgery is intravenous analgesia based on opioids. 
 
9. Fees and compensation for participating in this study 
There are no study-related costs for your participation in the study. Your child's de-
identified information and de-identified biological samples may be used to create products 
or provide health promotion services. If these situations occur, we will not tell you, pay you, 
or provide you or your family with any compensation. Most uses of biological samples and 
biological information do not result in a commercial product or benefit to anyone. 
You will not be paid or compensated for this study. 
 
10. Handling of research-related damages 
When your child's health condition suffers research-related damage while participating 
in this study, please inform the researcher (Dr. Guo Jingfei, contact number: 15810396387). 
We will take necessary medical measures promptly and compensate you and your child in 
accordance with the relevant laws and regulations of our country.  
 
11. Will my information be kept confidential? 
If you decide to have your child take part in this study, your participation in the study 
and your child's personal information in the study will be kept confidential. When using 
research data in this study, your child's personal information will be kept confidential and all 
information will be kept secure and used only for this study. Information in the research 

19 
 
database and samples will be strictly desensitized to remove personally identifiable 
characteristics, and information that may identify your child will not be disclosed to anyone 
other than the researchers without your permission. 
In order to ensure that the research is conducted in accordance with regulations, 
inspectors from the ethics committee, drug regulatory authorities, and health authorities 
may access the original medical records of research participants to verify the process of 
clinical research without violating the principle of confidentiality and relevant regulations.  
If the research results are published publicly, your child's personal information will not 
appear in any public medical records or publications, and we will not disclose this 
information to anyone or any institution. 
 
12. What rights do research participants have? 
Participation in this study is voluntary and you are free to decide whether to participate 
in this study. Regardless of whether you agree to participate in this study, it will not affect 
the routine clinical diagnosis and treatment you should receive during your hospital stay. 
You may refuse to participate at any time or have the right to withdraw from the study 
at any stage during the study without any reason, and you will not be subject to 
discrimination or unequal treatment. Medical treatment and rights will not be affected. 
If you want to withdraw from the research project during your participation, please 
notify the researcher, complete relevant pre-exit checks as required by the researcher, and 
complete the relevant withdrawal procedures as required. After withdrawal, the researcher 
will no longer continue to collect and use your children's experimental data, but the 
anonymized data collected before you exit will not be deleted or withdrawn. After you 
withdraw, your child may choose opioid analgesic treatment. If we discover new information 
related to your child's health and rights after you withdraw, we may contact you again. 
If you want to participate in this study, you need to read this informed consent form 
carefully and sign it after confirming that you fully understand the relevant issues. You will 
not lose any legal rights granted to you by law after signing this document. 
During the research process, you have the right to obtain new information about this 
research, and you also have the right to obtain the informed consent form and re-sign the 
new version of the informed consent form. 
If you agree to sign this document, our hospital will obtain your biological samples and 
research data free of charge. Our researchers and the joint research institutions participating 
in this study can use your biological samples and research data for the purpose of this 
research.  
 
13. Circumstances and reasons under which research participants may be terminated 
If your child has the following circumstances during the study, the researcher will ask 
your child to withdraw from this study: 
(1) After randomization, serious violations of the inclusion criteria or exclusion criteria 
are found, affecting the evaluation of intervention efficacy; 
(2) Serious complications or special physiological change occurs, and it is not suitable 
to continue the trial; 
(3) If allergic reactions or serious adverse events occur, the trial should be stopped 

20 
 
according to the doctor’s judgment; 
(4) The blinding is broken midway due to various reasons. 
The study sponsor or regulatory agency may also terminate the study during the 
research period. If this study is terminated prematurely, we will notify you promptly and 
your researcher will provide recommendations for the next treatment plan based on your 
child's health condition. For study participants who drop out midway, for safety reasons, we 
have a final follow-up plan, and you have the right to refuse. In addition, you are expected 
to return all unused study drugs/study equipment to the researchers. If we find new 
information related to your health and rights after you drop out, we may contact you again. 
Once you withdraw from the study, we won’t collect new data about your child. The 
researcher will closely preserve the relevant information before withdrawing from the study 
until it is finally destroyed and will not continue to use or disclose it. However, in rare cases, 
this information needs to be used. For example, when government supervision departments 
conduct supervision, inspections, and statistics, they will ask to see all research information, 
which will include information related to your participation in the research at that time. 
 
14. Are you willing to participate in future research? 
If you agree, we would like to keep your child's remaining samples for testing during 
the study. In addition, we would like to follow up with your child long-term after the study 
ends to learn about health status and medication information (this may be considered if 
long-term follow-up is involved). Your child's remaining de-identified biological samples, 
research data, clinical diagnosis and treatment data (including but not limited to medical 
records, imaging data, clinical examination and monitoring data etc.) and follow-up data 
will continue to be used for subsequent genetic and non-genetic medical research on 
cardiovascular diseases in order to explore the causes, mechanisms and influencing factors 
of disease occurrence and evolvement, and to develop disease prevention, diagnosis and 
treatment measures. If you do not agree, after completing this study, your child's remaining 
research samples will be destroyed according to clinical routines, and the research data and 
clinical diagnosis and treatment data will be kept for a specified number of years in 
accordance with national regulations and will be kept strictly confidential. 
Participating in future research will not increase your additional risk or financial burden. 
All samples and data from future research will be properly kept at our hospital and kept 
strictly confidential. You may voluntarily choose whether to participate in future studies and 
may withdraw from the study at any time by contacting the researchers. 
 
15. Who should I contact if I have questions or difficulties? 
You can ask any questions about this study at any time and get corresponding answers, 
including any discomfort that may occur during the study, please contact researcher Guo 
Jingfei at 15810396387. 
If you have any questions about your rights, please contact the Ethics Committee of 
Fuwai Hospital, Tel: 010-88396281, 010-88396282. 
Thank you for taking the time to read this informed consent form. If you and your 
family members agree to participate in this study after full consideration, we hope that you 
and your family members will complete this study in accordance with the requirements of 

21 
 
the researchers. Before participating in this study, please complete and sign the last page of 
this document (signature page) with your researcher in duplicate, with each of you and the 
hospital keeping one copy of the signed document. 
 
Signature page 
Statement of research participants 
I have carefully read, understood and agreed to all the terms of this informed consent 
form. 
I have been informed of the research purpose, content, and procedures of this 
research/clinical trial, possible risks of the research/trial, research compensation, and my 
rights, etc.; I have had sufficient time and opportunity to ask questions and have received 
satisfactory answers.  
I agree to participate in this study and authorize your hospital to collect my biological 
samples and research data for this study. 
I promise that the information I provide is true; if I provide false information, I promise 
to be responsible for the consequences. 
I have also been told who to contact if I have questions or want further information. 
I confirm that the contact information left at the signature office is my own valid 
contact information. If I change my contact information, I should inform your hospital in 
time. Otherwise, I am willing to bear the consequences of being unable to contact and 
receive notifications. 
I know that I can withdraw from this study at any time without affecting my medical 
treatment and rights. I also know that the researcher may suspend/terminate my continued 
participation in this study at any time. 
I will be given an original copy of this informed consent form, signed by myself and the 
researcher. 
I agree to participate in this study. 
Do you agree to participate in future research □ Agree □ Disagree (please 
choose) Donate the remaining samples for testing, clinical diagnosis and treatment 
data, and long-term follow-up data for future research. I authorize researchers and 
joint research units of related medical research projects use my approved anonymous 
remaining samples and data for cardiovascular-related genetic and non-genetic 
medical research. (If there is content for future research in the text, you may consider 
adding this wording) 
Name of the Study Participant:                         Signature： 
                                                   Date: 
(If the research participant is a person without capacity or with limited capacity, a 
guardian’s signature is required. If the research participant is a person with full capacity for 
civil conduct, this part can be deleted) 
Name of the guardian:                                Signature: 
                                                   Date: 
I confirm that the information in the informed consent form has been correctly 
interpreted and understood by the research participant and/or the research participant's 

22 
 
legal representative. Study participants voluntarily agreed to participate in this study. 
Signature of impartial witness [if applicable]:              Date: 
 
Statement of the investigators 
I confirm that the details of this study have been explained to the study participants. 
Including their rights, benefits and risks, the research participants' questions were answered, 
and a signed copy of the informed consent form was given to them. The research 
participants voluntarily participated in this study. 
Name of the investigator:                              Signature: 
                                                    Date: