2024 Clinical Practice Guidelines for Postoperative Pain Management in Adults

Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
Contents lists available at ScienceDirect
Journal of Anesthesia and Translational Medicine
journal homepage: www.keaipublishing.com/en/journals/jatmed
Review Article
Clinical practice guidelines for postoperative pain management in adults
(2024 edition)☆
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Xiangdong Chena,1, Qinjun Chub,1, Yunshui Pengc, Yaolong Chend, Alan D. Kayee, Henry Liuf,
⁎
⁎⁎
⁎⁎⁎
Jianjun Yangg,h, , Tianlong Wangi, , Weifeng Yuj,k, , Pain Group of the Chinese Society of
Anesthesiology2
a
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, China
The Second Hospital of Hebei Medical University, Editorial Department of Chinese Journal of Anesthesiology, Shijiazhuang 050071, China
d
Evidence‑Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
e
Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, Louisiana State University School of Medicine-Shreveport, 1501 Kings Highway,
Shreveport, LA 71130, USA
f
Department of Anesthesiology and Critical Care, Perelman School of Medicine, The University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
g
Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
h
Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
i
Department of Anesthesiology and Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
j
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
k
Department of Anesthesiology, The First Affiliated Hospital of Wenzhou University, Wenzhou 325000, China
b
c
A R T I C L E
Keywords:
Adults
Pain
Postoperative
Analgesia
Guideline
I N F O
A B S T R A C T
Acute pain differs in many aspects from chronic pain states and can arise from various etiologies. Recent years
have seen advancements in postoperative acute pain management, which is a critical component of perio­
perative care. These strategies play a key role in enhancing recovery after surgery (ERAS) with goals of reducing
postoperative opioid consumption and shortening hospital stay durations. To further standardize postoperative
pain management for adult patients in China，the Guidelines Working Group has developed the Clinical Practice
Guideline for Postoperative Pain Management in Adults (2024 Edition). These guidelines were formulated in
accordance with World Health Organization handbook for guideline development and the Guidance Principles
for Developing/Revising Clinical Guidelines in China (2022 Edition). These guidelines consist of 33 evidencebased recommendations for 17 clinical questions on postoperative pain management. We provide re­
commendations pertaining to preoperative education, risk assessment, selection of analgesic modalities, and
management of adverse effects. We also provide some principles of analgesia strategy including: using pre­
emptive or multimodal analgesia; foundation; regional blocks; patient-controlled intravenous analgesia; and
opioid sparing. By enhancing the scientific rigor of postoperative pain management， the guidelines aim to
provide healthcare professionals with a clear decision-making framework, ultimately improving patient out­
comes.
☆
This article is published simultaneously in Chinese Journal of Anesthesiology (Chinese) and Journal of Anesthesia and Translational Medicine (English) as a bilingual
version under a collaborative agreement, with identical results and conclusions.
⁎
Corresponding author at: Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,
China.
⁎⁎
Corresponding author at: Department of Anesthesiology and Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
⁎⁎⁎
Corresponding author at: Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
E-mail addresses: [email protected] (J. Yang), [email protected] (T. Wang), [email protected] (W. Yu).
1
Xiangdong Cheng and Qinjun Chu have contributed equally as first authors.
2
See appendix for the Pain Group of the Chinese Society of Anesthesiology.
https://doi.org/10.1016/j.jatmed.2025.09.001
Received 12 July 2025; Received in revised form 26 August 2025; Accepted 2 September 2025
Available online 19 September 2025
2957-3912/© 2025 The Author(s). Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
X. Chen, Q. Chu, Y. Peng et al.
Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
Development15 and the Guidance Principles for Developing/Revising
Clinical Guidelines in China (2022 Edition).16 The guideline develop­
ment plan and the final document were prepared based on the stan­
dards from the appraisal of guidelines for research and evaluation II
(AGREE II),17 the reporting items for practice guidelines in healthcare
(RIGHT),18 and the scientific, transparent and applicable rankings
(STAR) tool for clinical practice guidelines.19
Introduction
Postoperative pain encompasses a range of physiological, psycholo­
gical, and behavioral responses that patients experience following sur­
gical injuries, typically peaking within 24–72 h after surgery.1,2 Its ori­
gins are multifactorial: surgical mechanical injury directly stimulates
superficial or deep nociceptors, resulting in somatic pain1,3; traction,
distension, ischemia, spasm, and inflammation of thoracic or abdominal
viscera during surgery elicit visceral pain4; tissue damage and the sub­
sequent inflammatory response give rise to inflammatory pain; and nerve
injury or abnormal neural signaling can lead to neuropathic pain.5 Pre­
operative anxiety, depression, and fear can further modulate pain in­
tensity.5,6 Given the variability in the type of surgical injuries, patient
characteristics, and postoperative functional exercise requirements, pain
management strategies must be individualized. Effective management
should address these diverse mechanisms while minimizing adverse ef­
fects, thereby optimizing patients’ physical, psychological, and physio­
logical functions and promoting postoperative recovery.1
Despite significant advancements in clinical medicine, the in­
troduction of novel analgesic drugs and techniques, and the rapid
evolution of pain-management models, perioperative pain control re­
mains suboptimal worldwide. A recent European study has shown that
72.8 % of patients experienced acute postoperative pain, with 48.7 %
suffering from moderate to severe pain.7 Similarly, a survey encom­
passing 26,193 surgical cases across 122 Chinese hospitals revealed that
the incidence of moderate to severe pain was as high as 48.7 % in the
first day postoperatively.8 Acute pain not only increases the risk of
complications and delays recovery but also prolongs hospital stays and
escalates medical care costs.9 Moreover, persistent pain can potentially
evolve into difficult-to-control chronic pain, which significantly impairs
quality of life.10 To enhance the quality of postoperative pain man­
agement, numerous guidelines and expert consensuses have been de­
veloped both internationally and domestically in recent years.1,11−13
However, variations in cultural differences, healthcare resources, the
availability of pain medications, and health policies can lead to dif­
ferent approaches in managing postoperative pain among patients.
While domestic consensuses are clinically pragmatic, they often to some
extent lack methodological rigor and rarely base their recommenda­
tions on systematic-review evidence.14 In contrast, formulating evi­
dence-based guidelines enables systematic evaluation and synthesis of
the most current clinical research, providing robust support for deci­
sion-making process, and promoting standardized, high-quality clinical
practice. In response to the needs and challenges of adult postoperative
pain management, the working group on this guideline has developed
the Clinical Practice Guideline for Adult Postoperative Pain Manage­
ment (2024 edition), taking into account China’s unique cultural con­
text, economic conditions, and clinical realities, while fully considering
patient preferences. It aims to enhance the scientific rigor and national
standardization of pain management, provide clear and actionable an­
algesic decision support for clinicians and nurses, and ultimately im­
prove patient outcomes.
Registration and protocol
This guideline has been registered in both Chinese and English on
the international Practice Guideline Registration for Transparency
(PREPARE) platform (http://guidelines-registry.cn/), with the regis­
tration number PREPARE-2024CN386. The protocol for this guideline
was published in the Chinese Journal of Anesthesiology, Issue 9, 2024.20
Guideline development working group
This guideline was initiated by the Pain Group of the Chinese
Society of Anesthesiology. Methodological support was provided by the
Institute of Health Data Science at Lanzhou University, WHO
Collaborating Center for Guideline Implementation and Knowledge
Translation, Research Unit of Evidence-Based Evaluation and
Guidelines, Chinese Academy of Medical Sciences, Lanzhou University,
an Affiliate of the Cochrane China Network, Lanzhou University GRADE
Center, and Evidence-Based Medicine Center, School of Basic Medical
Sciences, Lanzhou University. The working group included a steering
committee, consensus expert group, methodological group, evidence
assessment group, secretariat, external review expert panel, and patient
group. Responsibilities of each group are detailed in the protocol.20
Members consisted of multidisciplinary experts from anesthesiology,
surgery (orthopedic, general, and thoracic surgery), obstetrics and gy­
necology, clinical pharmacy, nursing, journal editing, evidence-based
medicine, and guideline methodology from various geographical re­
gions. The consensus expert panel played a key role in establishing core
development principles.
Conflict of interest management and funding
All members involved in the guideline development completed
conflict-of-interest declaration forms and managed any potential con­
flicts in accordance with the established conflict-of-interest manage­
ment policy. No financial or non-financial conflicts related to this
guideline were identified. The guideline received no industry funding
from pharmaceutical or device companies. Activities (meetings,
training, documentation) were conducted pro bono. The processes of
literature search, evaluation, evidence extraction, and systematic re­
views were funded by the Bethune Charity Foundation, which had no
role in recommendation development.
Collection and selection of clinical questions
Methods and processes for guideline development
The target population for this guideline comprises adult patients
aged 18 years and older who are undergoing inpatient surgical proce­
dures. The intended users of this guideline include clinicians, nursing
staff, and relevant scientific research personnel across various levels of
healthcare institutions.
The search team conducted systematic literature searches to identify
existing guidelines, consensus statements, and systematic reviews on
adult postoperative pain. Preliminary clinical questions were derived
from surveys/interviews with clinicians and anesthesiologists. After
deduplication and merging, clinical and methodological experts struc­
tured questions using population，intervention/exposure，compar­
ison，and outcome (PICO/PECO) frameworks. Through two Delphi
rounds and one consensus meeting, 17 questions were prioritized for
recommendations.
Methodology
Evidence retrieval, appraisal, and synthesis
This guideline was developed in accordance with the methods and
procedures outlined in the WHO Handbook for Guideline
Evidence selection followed this hierarchy: (1) Utilizing published
high-quality systematic reviews that were assessed using the A
Target population and user population
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X. Chen, Q. Chu, Y. Peng et al.
Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 tool,
provided that recent systematic reviews addressed the clinical questions
with high methodological quality.21 (2) Conducting new systematic
reviews based on randomized controlled trials (RCTs) assessed with the
Cochrane Risk of Bias (ROB) tool, if existing systematic reviews were
either absent or of poor methodological quality. (3) Including ob­
servational studies if RCTs unavailable. (4) Formulating recommenda­
tions based on expert consensus if neither RCTs nor observational evi­
dence existed.
Drafting and external review
The guideline was authored by the expert group in accordance with
the RIGHT reporting standards.18 Feedback for revision was provided
by five external reviewers. The steering committee then finalized and
approved the guideline.
Dissemination, implementation, and updates
The guideline is available in both Chinese (published in the Chinese
Journal of Anesthesiology) and English (published in the Journal of
Anesthesia and Translational Medicine). Dissemination and promotion
strategies include academic journal publications, national im­
plementation campaigns, and evaluation of guideline impacts after 1–2
years. The guideline will be updated five years post-publication, with a
focus on controversial areas or new evidence.
Database search and keywords
The databases searched included SinoMed, CNKI, WanFang,
Cochrane Library, PubMed, Embase, and Web of Science. Key terms
included "postoperative pain", "pain assessment", "perioperative an­
algesia", "multimodal analgesia", and "acute pain service", etc., com­
bined with terms related to research design and population. The search
period spanned from the inception of each database to June 1, 2024,
and was limited to articles published in Chinese and English.
Recommendations and basis for recommendations
A total of 33 recommendations are formed for 17 clinical questions
in postoperative pain management (Table 2).
Inclusion and exclusion criteria
Inclusion Criteria: (1) Population: Hospitalized surgical patients
aged ≥ 18 years. (2) Study Types: Systematic reviews, meta-analyses,
RCT, non-randomized controlled studies, cohort studies, case-control
studies, and cross-sectional studies relevant to adult postoperative pain
management.
Exclusion Criteria: (1) Duplicate publications. (2) Guidelines or
consensus protocols. (3) Studies unrelated to the clinical questions. (4)
Conference abstracts, reviews, commentaries. (5) Studies inaccessible
as full text or lacking relevant data related to the guideline issues.
Clinical question 1: what is the impact of preoperative pain education and
prehabilitation on postoperative pain?
Recommendation 1: We suggest providing preoperative pain
education for patients and their families, covering the adverse effects of
pain on the body, the importance of pain management, the use of pain
assessment tools, and pain treatment plans and their potential side ef­
fects. These may improve analgesic efficacy and enhance patient sa­
tisfaction (low-quality evidence, weak recommendation).
Recommendation 2: We suggest implementing preoperative pre­
habilitation measures for surgical patients, particularly those under­
going joint replacement surgery, including functional exercise, health
education, and psychological interventions, to improve postoperative
pain outcomes (low-quality evidence, weak recommendation).
Evidence summary: Preoperative pain education: A systematic
review developed by the evidence group included 53 RCTs (n = 6643).
Among these, 24 studies involved education on the impact of pain on
the body and the importance of pain management, 7 studies covered
knowledge of pain mechanisms, 11 studies dealt with the use of pain
assessment tools, 9 studies addressed pharmacological and non-phar­
macological pain management, and 5 studies included education on the
use of analgesic pumps. The results showed that, compared with the
Evidence certainty and recommendations strength
The certainty of evidence and the strength of recommendations
were graded using the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) system (Table 1).22,23 For re­
commendations without sufficient evidence, Good Practice Statements
(GPS)24 were formulated.
Recommendations formulation
The working group drafted 39 recommendations based on evidence
synthesis, patient values, economic analysis, and benefit-harm assess­
ment. After two Delphi rounds, 26 reached consensus (10 revised, 3
removed, 5 added). Final iterations yielded 33 recommendations.
Table 1
GRADE Evidence Certainty and Recommendation Strength.
Evidence certainty level
Symbol
Definition
High
Moderate
A
B
Low
Very low
C
D
We are very confident that the true effect lies close to that of the estimate of the effect.
We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there
is a possibility that it is substantially different.
Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of
effect.
Recommendation strength
Symbol
Definition
Strong
1
Weak
2
When the balance of benefits and harms is clearly favorable, the evidence is of high quality, patient values and preferences
are consistent, and the intervention is affordable, the recommendation is graded as strong.
•Clinicians: Nearly all will adopt the intervention.
•Policymakers: The recommendation will be implemented as standard in most settings.
•Patients: The vast majority will choose it; only a small minority will decline.
When the benefit-risk balance is uncertain, evidence quality is low, values and preferences vary widely, and costs are high,
the recommendation is graded as weak.
•Clinicians: Tailor decisions to individual patients, explicitly incorporating their values and preferences.
•Policymakers: Policy adoption should be preceded by broad stakeholder deliberation.
•Patients: While many may accept the intervention, a substantial proportion will not.
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
Table 2
Clinical questions and recommendations summary of clinical practice guideline for postoperative pain management in adults.
Clinical questions
Recommendations
1. Preoperative pain education and prehabilitation
Recommendation 1: It is suggested that preoperative pain education be provided to patients and their
families. This should cover the negative effects of pain, importance of pain management, the use of pain
assessment tools, pain treatment plans, and potential adverse effects. The goal is to improve analgesic
effectiveness and patient satisfaction (2C).
Recommendation 2: It is suggested that prehabilitation measures be implemented, including
preoperative exercises, health education, and psychological interventions. These measures are
particularly recommended for patients undergoing joint replacement surgery to enhance postoperative
analgesia (2C).
Recommendation 3: It is recommended to identify and address the following preoperative risk factors for
acute postoperative pain: young age, high BMI, preoperative depression, preoperative opioid use, and
high expectation of postoperative pain (1A); Female gender, sleep disorders, anxiety, pain
catastrophizing, preoperative pain history, diabetes, low education level, ASA classification of III or
higher (2B); Smoking history and pain sensitivity (2C).
Recommendation 4: Single-dimensional tools (Visual Analog Scale [VAS], Numerical Rating Scale
[NRS], Faces Pain Scale [FPS], Verbal Descriptor Scale [VDS])) are recommended for rapid assessment of
pain (2C).
Recommendation 5: Multi-dimensional tools (Brief Pain Inventory [BPI], McGill Pain Questionnaire
[MPQ]) (BPI, MPQ) are recommended for comprehensive assessment of pain (2B).
Recommendation 6: APS led by anesthesiologists, with multidisciplinary participation, is recommended
to improve analgesic effectiveness (2C).
Recommendation 7: Preemptive analgesia, particularly multimodal analgesia and nonsteroidal antiinflammatory drugs (NSAIDs), is recommended to reduce postoperative pain and opioid consumption
(2C).
Recommendation 8: Multimodal analgesia is recommended perioperatively to improve analgesia, reduce
opioid consumption (1C), lower nausea/vomiting incidence (2B), reduce sedation (1A), improve recovery
quality and patient satisfaction (2B), and shorten hospital stay (1A).
Recommendation 9: Acetaminophen (1B) and NSAIDs (1C) are recommended as foundational analgesics
in patients without contraindications, to improve analgesia and reduce opioid use.
Recommendation 10: The combined use of acetaminophen and NSAIDs is superior to monotherapy (2B).
Recommendation 11: Peripheral nerve blocks are recommended as an essential component of
multimodal analgesia, to reduce opioid use and nausea/vomiting and improve analgesic outcomes (1B).
Recommendation 12: Epidural analgesia is superior for thoracic and abdominal surgery analgesia but
requires caution due to potential side effects (2B).
Recommendation 13: Epidural analgesia offers no significant advantage over peripheral nerve blocks in
lower extremity surgeries and may increase urinary retention and length of hospital stay (2B).
Recommendation 14: Combining analgesics with different mechanisms is recommended for intravenous
analgesia to enhance synergistic analgesic effects and reduce adverse reactions (2D).
Recommendation 15: μ-receptor agonists are suggested for intravenous analgesic pumps (2D).
Recommendation 16: Dexmedetomidine is recommended as an adjunct in intravenous analgesic pumps
(2D).
Recommendation 17: Regional blocks and/or non-opioids (acetaminophen, NSAIDs, N-methyl-Daspartic acid (NMDA) antagonists, α2-agonists, dexamethasone, lidocaine) are recommended to reduce
opioid use and adverse effects and improve satisfaction (1C).
Recommendation 18: Close respiratory monitoring is recommended (GPS).
Recommendation 19: In case of respiratory depression or sedation, reduce or stop opioids, maintain
airway, administer naloxone or nalmefene if needed (GPS).
Recommendation 20: Reduce opioid dosage for elderly patients to prevent sedation (GPS).
Recommendation 21: For low/moderate-risk patients, prophylactic antiemetics (5-HT3 antagonists,
steroids, dopamine antagonists, NK−1 antagonists) are recommended (1A); high-risk patients should
receive combinations (1A).
Recommendation 22: Orthopedic surgery and preoperative pain are recommended risk factors for
rebound pain (1A).
Recommendation 23: Acetaminophen is suggested to prevent breakthrough pain (2C).
Recommendation 24: Opioids are recommended for management of breakthrough pain (2D).
Recommendation 25: Dexamethasone and ketamine/esketamine are recommended intraoperatively for
high-risk rebound pain (2A).
Recommendation 26: Continuous nerve blocks or multimodal analgesia are suggested for high-risk
rebound pain (2D).
Recommendation 27: Surgery-type-based individualized analgesia is recommended (1C).
2. Preoperative factors influencing acute postoperative pain
3. Assessment tools to evaluate postoperative pain
4. Impact of Acute Pain Services (APS) on postoperative analgesia
outcomes
5. Impact of preemptive analgesia on postoperative pain
6. Advantages of multimodal analgesia in postoperative pain
management
7. Effectiveness of acetaminophen and/or NSAIDs for postoperative
analgesia
8. Effectiveness of peripheral nerve blocks for postoperative pain
management
9. Effectiveness of neuraxial analgesia (epidural or spinal) for
postoperative pain management
10. Appropriate drug selection for intravenous patient-controlled
analgesia pumps
11. Impact of opioid-sparing analgesia on postoperative recovery
12. Prevention and management of common opioid-related adverse
effects in pain management
13. Risk factors for postoperative breakthrough pain and rebound
pain, and strategies for prevention and management
14. Impact of surgery-type-based pain management strategies on
postoperative analgesia
15. Analgesic regimens for postoperative pain management in day
surgery patients
16. Analgesic regimens for postoperative pain management in elderly
patients
17. Risk factors for transitioning from acute to chronic pain and the
role of transitional pain services in prevention
Recommendation 28: Acetaminophen or NSAIDs recommended for mild pain (GPS).
Recommendation 29: For day surgery patients with moderate to severe pain, acetaminophen, NSAIDs
(2B) combined with local infiltration (2C) or peripheral nerve blocks (2C) are recommended, with opioids
if needed.
Recommendation 30: NSAIDs (2C), acetaminophen (2C), and peripheral nerve blocks (2D) are
recommended for postoperative analgesia in elderly patients without contraindications.
Recommendation 31: Opioids combined with dexmedetomidine preferred over opioids alone in elderly
(2D).
Recommendation 32: Recognize risk factors for chronic pain: moderate/severe postoperative pain (1A);
young age, female gender, smoking, anxiety, depression, preoperative pain, long surgery duration (2B);
incision infection, pain catastrophizing (2C).
Recommendation 33: Transitional pain services are recommended to prevent chronic pain and reduce
long-term opioid use (2C).
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
control group (n = 3130), patients who received preoperative pain
education (n = 3513) had lower pain scores at 24 h and 48 h post­
operatively (mean difference (MD) −1.65 points; 95 % confidence in­
terval (CI) −2.13 to −1.17; MD −1.06 points; 95 % CI −1.46 to
−0.67). There was no statistically significant difference in pain scores
between the two groups in 72 h postoperatively (MD −0.38 points;
95 % CI −0.76 to 0.01). In addition, there was no statistically sig­
nificant difference between the preoperative pain education group and
the control group in postoperative opioid consumption (morphine
equivalent dose) at 24 h, 48 h, and 72 h (MD −0.11 mg; 95 % CI −0.55
to 0.33; MD −0.45 mg; 95 % CI −0.97 to 0.06; MD −0.18 mg; 95 % CI
−0.43 to 0.06).
Preoperative prehabilitation: Two published systematic reviews
were included, encompassing 56 RCTs. Of these, 23 studies included
preoperative education, 26 included strength training, 21 included
flexibility training, 12 included balance training, 5 included aerobic
exercise, and 2 included psychological intervention. A systematic re­
view published in 2023 (total of 28 RCTs, n = 1823),25 examined
surgeries including joint replacement (24 studies), spine surgery (2
studies), carpal tunnel syndrome (1 study), and colon surgery (1 study).
The results showed that patients who underwent prehabilitation had
lower pain intensity at ≤ 2 months (standardized mean difference
(SMD) −0.31; 95 % CI −0.53 to −0.10) and at 3–5 months (SMD
−0.41; 95 % CI −0.68 to −0.14) postoperatively, compared with
those who did not undergo prehabilitation. However, there was no
statistically significant difference in pain intensity at ≥ 6 months
postoperatively (SMD −0.11; 95 % CI −0.29 to 0.08). Another sys­
tematic review on joint replacement surgery published in 2024 (28
RCTs, n = 2296),26 indicated that preoperative prehabilitation can re­
duce postoperative pain scores at 4–6 weeks after joint replacement
(SMD–0.76; 95 % CI –1.45 to –0.07).
Patient preferences and values: Three patients considered pre­
operative education to be extremely important, two considered it re­
latively important, and all five patients believed that preoperative
prehabilitation was extremely important.
Recommended principle: Studies have shown that preoperative
pain education can guide patient treatment and rehabilitation,27 in­
crease patients’ understanding of pain, help them report pain, and al­
leviate anxiety and depression. It can also correct misunderstandings
about pain management and side effects of analgesics among patients
and their families, improve patient adherence, and thereby effectively
reduce postoperative pain.28,29 In recent years, both domestic and in­
ternational guidelines and expert consensus have recommended pro­
viding personalized preoperative pain education to patients and their
families, including postoperative pain management plans and goals, the
necessity of postoperative pain treatment, commonly used pain as­
sessment tools, and available analgesic methods.11,30 In addition, re­
search has shown that educating patients on the principles, structure,
and usage of patient-controlled analgesia (PCA) pumps and involving
patients and their families in the pain management process can improve
analgesic effects and increase patient satisfaction.31 Forms of pre­
operative pain education include face-to-face teaching, videos, audio
materials, and online education.11 However, the methods used in
clinical practice are often relatively limited and influenced by factors
such as the experience and communication skills of healthcare provi­
ders and the educational level, comprehension, and cognitive capacity
of patients. Therefore, the effectiveness of preoperative pain education
can vary significantly.32 In recent years, new educational formats such
as micro-videos and scenario simulations combined with ProblemBased Learning (PBL) have begun to be applied in clinical settings;
high-quality clinical research is needed in the future to evaluate the
impact of different educational forms on postoperative pain.
Preoperative prehabilitation mainly involves a multidisciplinary
team composed of surgeons, anesthesiologists, nutritionists, re­
habilitation specialists, psychologists, and nurses who deliver multi­
modal interventions before surgery to improve patients’ ability to
withstand surgical risks, improve surgical outcomes and postoperative
quality of life, and reduce medical costs.33 Preoperative exercise can
improve patients’physical function before surgery, promote skeletal
muscle fiber growth, and accelerate postoperative wound healing.25 It
can also improve immune function, reduce postoperative pain, lower
postoperative complications, and enhance quality of life.34–36 Health
education and psychological intervention can effectively alleviate pa­
tients’ anxiety and depression, thereby reducing postoperative
pain.37,38 The 2021 Chinese Clinical Practice Guidelines for enhanced
recovery after surgery39 and the 2022 Expert Consensus on pre­
habilitation management in thoracic surgery40 both recommend in­
dividualized prehabilitation measures, such as smoking cessation, cor­
rection of preoperative anemia, preemptive analgesia, preoperative
exercise, inflammation control, nutritional optimization, and psycho­
logical intervention, to improve patients’ perioperative functional
status, shorten hospital stays, and reduce postoperative complications.
Currently, prehabilitation strategies are mainly applied in orthopedic,
thoracic, and abdominal surgeries.25 However, how prehabilitation
strategies affect the prognosis of patients undergoing different surgical
procedures still requires high-quality clinical research to provide evi­
dence, helping clinicians to develop individualized prehabilitation
measures for patients.
Clinical question 2: what preoperative factors influence acute postoperative
pain?
Recommendation 3: It is recommended to focus on preoperative
risk factors for acute postoperative pain: younger age, higher body mass
index (BMI), preoperative depression, preoperative opioid use, and
higher expectations of postoperative pain (high-quality evidence,
strong recommendation); female sex, preoperative sleep disorders,
preoperative anxiety, preoperative pain catastrophizing, preoperative
pain history, diabetes history, lower educational level, and ASA clas­
sification of III or above (moderate-quality evidence, weak re­
commendation); smoking history and preoperative pain sensitivity
(low-quality evidence, weak recommendation).
Evidence summary: A total of 157 Chinese- and English-language
cohort studies were included by the evidence group, of which 102 pro­
vided regression analysis results adjusted for confounding factors. These
results were pooled for analysis, and ultimately 16 preoperative painrelated factors were identified: Age (28 studies, n = 26,393) is a pro­
tective factor for acute postsurgical pain (APSP) (odds ratio (OR) 0.98;
95 % CI 0.97 to 0.99); BMI (18 studies, n = 13,650) is a risk factor for
APSP (OR 1.10; 95 % CI 1.05 to 1.16); compared with male patients,
females (34 studies, n = 91,188) have a higher risk of APSP (OR 1.43;
95 % CI 1.27 to 1.62); lower educational level (below secondary edu­
cation) is associated with increased APSP risk (5 studies, n = 963) (OR
1.62; 95 % CI 1.02 to 2.56), ASA classification of grade III and above (7
studies, n = 4764) (OR 1.34, 95 % CI 1.02 to 1.76), smoking (9 studies,
n = 38,439) (OR 1.37; 95 % CI 1.12 to 1.66), and preoperative diabetes
(8 studies, n = 42,085) (OR 1.42; 95 % CI 1.29 to 1.56) are all associated
with increased APSP risk; whereas patient marital status (4 studies,
n = 1966) (OR 1.48; 95 % CI 0.86 to 2.56) and history of alcohol use (5
studies, n = 39,317) (OR 1.38; 95 % CI 0.78 to 2.38) are not significantly
associated with APSP risk. Patients’ preoperative psychological sta­
te—including preoperative depression (10 studies, n = 6688) (OR 1.89;
95 % CI 1.52 to 2.36), preoperative anxiety (17 studies, n = 3510) (OR
2.04; 95 % CI 1.66 to 2.51), and preoperative sleep disorders (8 studies,
n = 2142) (OR 1.97; 95 % CI 1.53 to 2.53)—is associated with increased
APSP risk; in addition, preoperative pain-related factors are also asso­
ciated with elevated APSP risk, including preoperative pain (27 studies,
n = 84,594) (OR 1.82; 95 % CI 1.52 to 2.18), preoperative pain cata­
strophizing (14 studies, n = 2781) (OR 1.07; 95 % CI 1.03 to 1.10),
preoperative use of opioids (5 studies, n = 35,813) (OR 1.56; 95 % CI
1.29 to 1.90), and expectations for postoperative pain (3 studies,
n = 1664) (OR 2.75; 95 % CI 1.55 to 4.88).
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A meta-analysis including 50 prospective cohort studies41 confirmed
that pressure pain threshold (12 studies, n = 1182) (correlation (r)
−0.27; 95 % CI 0.37 to −0.16) and electrical pain threshold (6 studies,
n = 485) (r − 0.23; 95 % CI −0.35 to −0.10) are negatively correlated
with APSP; total pain time (3 studies, n = 405) (r 0.20; 95 % CI 0.04 to
0.34) and the Pain Sensitivity Questionnaire (5 studies, n = 608) (r
0.28; 95 % CI 0.15 to 0.41) are positively correlated with APSP.
Rationale for recommendation: The incidence and severity of
APSP are influenced by multiple factors such as demographic char­
acteristics, comorbidities, and psychological status.42,43 A 2009 sys­
tematic review showed that preoperative pain, anxiety, age, and type of
surgery were the four most important predictors of APSP.44 A sys­
tematic review pointed out the association of APSP with preoperative
anxiety, pain catastrophizing, pain expectation, and depression.37 Pain
catastrophizing is an exaggerated negative cognitive and emotional
response to actual or anticipated pain,45 which can lead to excessive
fear of pain, avoidance of physical activity, and heightened pain vigi­
lance, thereby contributing to the occurrence of pain. A 2019 sys­
tematic review identified nine risk factors for predicting APSP in adults:
young age, female sex, smoking, history of depression, history of an­
xiety, sleep disturbance, high BMI, preoperative pain, and preoperative
use of opioids.46 The evidence group synthesized 16 potentially re­
levant preoperative risk factors, among which 14 were associated with
APSP, while alcohol use and marital status were not significantly as­
sociated. In addition, a 2024 systematic review indicated that pre­
operative pain sensitivity is positively correlated with APSP.41 There­
fore this guideline recommends 15 preoperative risk factors to be
considered. Identifying APSP-related risk factors is crucial for early
prevention, intervention, and individualized treatment of APSP,
thereby reducing short- and long-term postoperative pain-related
complications and accelerating postoperative recovery.
indicated that BPI better captures psychological features and is thus
recommended for assessing postoperative pain. Similarly, MPQ also
showed positive evaluations in internal consistency, reliability, and
structural validity.
Patient Values and Preferences: Four patients strongly agreed that a
good pain assessment tool should include: pain intensity, pain duration,
pain characteristics, triggers or relieving factors, and the impact of pain
on daily life; one patient expressed moderate agreement with these
contents. Regarding tool preference, two patients supported using
unidimensional scales for rapid assessment, two supported using mul­
tidimensional scales for comprehensive evaluation, and one expressed
acceptance of both.
Rationale for recommendation: Pain is a subjective experience
influenced by multiple factors. Selecting an appropriate assessment tool
to accurately evaluate patients’ pain helps identify their responses to
postoperative pain treatment and adjust the treatment plan accord­
ingly.12 Common clinical unidimensional tools include the VAS, NRS,
and FPS, while multidimensional tools include BPI and MPQ.49 These
tools have different scopes of application, each with its own advantages
and disadvantages. Unidimensional tools are simple and quick and are
recommended by previous guidelines for postoperative pain manage­
ment,49 but they are insufficient for comprehensive pain assessment
and may lead to issues such as over- or under-use of analgesics.50
Multidimensional assessments cover pain location, nature, dynamic
changes, and its impact on emotions, sleep, comfort, and psychology,
providing a more comprehensive, accurate, and scientific evaluation of
postoperative pain.51 The 2024 UK Consensus on Perioperative Pain
Management in Adults emphasized function-based pain assessment.13
Additionally, the choice of pain assessment tool should fully consider
the preferences of the user to minimize variation in assessment.52 The
BPI is better at capturing psychological characteristics and is re­
commended for postoperative pain assessment, though there is a lack of
relevant studies on its suitable population.48 Therefore, based on the
available evidence, this guideline recommends that healthcare provi­
ders weigh the pros and cons and select an appropriate assessment tool:
for rapid assessment, unidimensional tools may be used; for compre­
hensive assessment, multidimensional tools are preferred.
Clinical question 3: which assessment tools can more accurately evaluate
postoperative pain?
Recommendation 4: It is recommended to use unidimensional pain
assessment tools for rapid evaluation of postoperative pain intensity,
such as the visual analog scale (VAS), numeric rating scale (NRS), faces
pain scale (FPS), or verbal descriptor scale (VDS) (low-quality evidence,
weak recommendation).
Recommendation 5: It is recommended to use multidimensional
pain assessment tools for comprehensive evaluation of postoperative
pain, such as the brief pain inventory (BPI) or McGill pain questionnaire
(MPQ) (moderate-quality evidence, weak recommendation).
Evidence summary: A 2022 systematic review of unidimensional
pain assessment tools (31 studies in total, n = 12,498, including 1 RCT,
4 secondary analyses of RCTs, 4 cross-sectional studies, 5 clinical stu­
dies, 7 descriptive studies, and other types of research).47 The feasi­
bility and interpretability of the study methods were critically ap­
praised using the modified Newcastle-Ottawa Scale, and for validation
studies, the methodological quality was evaluated using the consensusbased standards for the selection of health measurement instruments
(COSMIN). The evaluation focused on validity, reliability, and respon­
siveness of unidimensional pain assessment tools represented by VAS,
NRS, FPS, and VDS. The results showed that there was no evidence
indicating that any one unidimensional tool possessed superior mea­
surement characteristics in assessing postoperative pain. A 2021 sys­
tematic review of multidimensional pain assessment tools (17 studies in
total, n = 15,820, including 15 cross-sectional studies and 2 secondary
analyses based on RCTs),48 used COSMIN methodological quality
standards to assess the quality of five commonly used multidimensional
clinical pain scales: BPI, MPQ, American Pain Society Patient Outcome
Questionnaire-Revised (APS-POQ-R), Hospital Pain Outcomes Index
(HPOI), and Quality Improvement in Postoperative Pain ManagementPostoperative Pain (QUIPS-POP). The assessment focused primarily on
three key aspects: validity, reliability, and responsiveness. The results
Clinical question 4: what is the impact of acute pain service on postoperative
analgesic outcomes?
Recommendation 6: It is recommended to establish an acute pain
service (APS) to improve postoperative analgesic outcomes.
Postoperative pain management requires multidisciplinary collabora­
tion, and an APS model led by anesthesiologists with multidisciplinary
participation is more beneficial for managing postoperative pain (lowquality evidence, weak recommendation).
Evidence summary: A network meta-analysis conducted by the
evidence group, (34 RCTs, n = 5393) compared the effects of four pain
management models on postoperative pain scores: traditional pain
management, APS models led by anesthesiologists or nurses, APS
models led by anesthesiologists with multidisciplinary participation,
and pain management multidisciplinary team (pMDT) models. The re­
sults showed that the APS model primarily led by anesthesiologists or
nurses (SMD −0.89; 95 % CI −1.38 to −0.39), the APS model led by
anesthesiologists with multidisciplinary participation (SMD −2.00;
95 % CI −2.48 to −1.52), and the pMDT model (SMD −1.12; 95 % CI
−1.47 to −0.77) all resulted in lower 24-hour postoperative VAS
scores compared with traditional pain management. Furthermore, the
APS model led by anesthesiologists with multidisciplinary participation
resulted in lower average postoperative VAS scores compared to the
APS model led by anesthesiologists or nurses (SMD −1.11; 95 % CI
−1.56 to −0.65), and lower 24-hour postoperative VAS scores com­
pared to the pMDT model (SMD −0.87; 95 % CI −1.47 to −0.28).
Patient Values and Preferences: Three patients considered APS to be
very important, while two patients considered it relatively important.
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Regarding acute pain management models, all five patients believed
that the pMDT model was superior to other models.
Rationale for recommendation: As a model for postoperative
analgesia management, APS has been increasingly adopted worldwide
since its introduction in 1988,53 with hospitals establishing APS teams
that help reduce postoperative pain, decrease opioid usage and chronic
postoperative pain, and improve patient experience.54 However, the
structure and function of APS vary greatly among hospitals, influenced
by factors such as staffing and resources,55 with fewer than half of APS
programs meeting minimum standards—such as designated personnel,
twice-daily APS rounds, and complete pain management records.56
Current APS models include: anesthesiologist- or nurse-led models,
anesthesiologist-led models with multidisciplinary participation (in­
cluding anesthesia nurses and surgeons), and pMDT models.57–59 Re­
lated to shortages of anesthesiologists, few patients benefit from an­
esthesiologist-led models; nurse-led models may suffer from insufficient
supervision by anesthesiologists, leading to limited analgesic options
and suboptimal quality.59 In contrast, the APS model led by anesthe­
siologists with multidisciplinary participation emphasizes that an­
esthesia nurses assess postoperative pain under anesthesiologist su­
pervision, anesthesiologists promptly adjust analgesic regimens, and
surgeons actively participate.60 This model fosters communication and
collaboration among anesthesiologists, surgeons, and nurses, ensuring
both efficacy and safety of analgesia, and can improve patient sa­
tisfaction with pain control. The pMDT model relies on a multi­
disciplinary team—including anesthesiology, surgery, nursing, re­
habilitation, and pharmacy—to formulate and implement perioperative
pain management strategies. However, it requires a significant work­
force to establish effective communication and feedback mechanisms,59
which currently poses challenges for broader implementation of this
model.
interventions (7 times), lornoxicam (5 times), intrathecal injection (4
times), ibuprofen (3 times), and parecoxib (3 times). In resting pain
scores at 6 h, 12 h, and 24 h postoperatively, preoperative use of two or
more analgesic drugs or interventions consistently ranked first among
all interventions. Compared with placebo or no intervention, the com­
bination of two or more drugs or interventions significantly reduced
resting pain scores at 6 h (MD −1.79 points; 95 % CI −2.08 to −1.51),
12 h (MD −1.55 points; 95 % CI −1.78 to −1.32), 24 h (MD −1.23
points; 95 % CI −1.40 to −1.05), and 48 h (MD −2.94 points; 95 % CI
−3.76 to −2.11), and reduced cumulative opioid consumption at 12 h
(MD −22.61 mg; 95 % CI −38.91 to −6.32 mg), 24 h (MD −34.76 mg;
95 % CI −41.70 to −27.82 mg), and 48 h (MD −39.60 mg; 95 % CI
−48.45 to −30.74 mg). Preoperative lornoxicam significantly reduced
resting pain scores at 6 h (MD −1.25 points; 95 % CI −2.01 to −0.49),
12 h (MD −0.95 points; 95 % CI −1.37 to −0.52), 24 h (MD −0.87
points; 95 % CI −1.18 to −0.55), and 48 h (MD −0.73 points; 95 % CI
−1.24 to −0.22), and reduced cumulative opioid consumption at 12 h
(MD −19.22 mg; 95 % CI −32.08 to −6.36), 24 h (MD −35.48 mg;
95 % CI −46.73 to −24.24), and 48 h (MD −65.27 mg; 95 % CI
−83.13 to −47.42). Preoperative ibuprofen significantly reduced
resting pain scores at 6 h (MD −1.62 points; 95 % CI −2.70 to −0.54),
12 h (MD −1.26 points; 95 % CI −2.09 to −0.43), and 24 h (MD
−1.08 points; 95 % CI −1.69 to −0.47). Preoperative parecoxib sig­
nificantly reduced cumulative opioid consumption at 12 h (MD
−17.92 mg; 95 % CI −30.98 to −4.86), 24 h (MD −35.06 mg; 95 % CI
−43.90 to −26.22), and 48 h (MD −78.66 mg; 95 % CI −95.60 to
−61.72). Preoperative intrathecal injection significantly reduced
resting pain scores at 12 h (MD −0.87 points; 95 % CI −1.58 to −0.07)
and 24 h (MD −0.98 points; 95 % CI −1.58 to −0.38), and reduced
cumulative opioid consumption at 12 h (MD −69.83 mg; 95 % CI
−93.34 to −46.33), 24 h (MD −52.54 mg; 95 % CI −62.46 to
−42.62), and 48 h (MD −81.38 mg; 95 % CI −97.11 to −65.65).
Patient Values and Preferences: After comparing the advantages and
disadvantages of preemptive analgesic measures or drugs, all five pa­
tients preferred receiving preemptive analgesia before surgery and se­
lected NSAIDs as the drug of choice. Four patients accepted the com­
bined use of two or more analgesic drugs or interventions, while one
patient did not.
Rationale for recommendation: Preemptive analgesia is a pain
management strategy that begins before surgery and continues post­
operatively, aiming to reduce peripheral and central sensitization
caused by noxious stimuli during the perioperative period, thereby
lowering pain intensity and the need for analgesics.62,63 Since both
preoperative pain and surgical incisions can induce central sensitiza­
tion, the preoperative phase of preemptive analgesia should not be
overlooked. Preoperative preemptive analgesic measures include
neuraxial analgesia, local infiltration, opioids, NMDA receptor antago­
nists, NSAIDs, etc.64 Based on the network meta-analysis conducted by
the evidence group, the top five interventions across seven outcome
indicators were identified and recommended. Multimodal analgesia
involving the combination of two or more drugs or interventions may
exert additive or synergistic effects, reduce the transmission of noxious
stimuli to the central nervous system, and achieve the goal of pre­
emptive analgesia.2 The use of NSAIDs as a preemptive analgesic before
surgery can reduce postoperative pain intensity and opioid consump­
tion, as well as the incidence of adverse effects such as postoperative
nausea and vomiting (PONV).65,66 Although preoperative intrathecal
injection can improve postoperative analgesia,67–69 the guideline
“Postoperative Pain Management Based on Surgical Type” recommends
administering 50–100 µg intrathecal morphine before cesarean section
to provide postoperative analgesia.70 However, evidence in other types
of surgery is relatively limited. Therefore, this guideline does not re­
commend it at present, and further high-quality studies are needed in
the future.
Clinical question 5: what is the impact of preemptive analgesia on
postoperative pain?
Recommendation 7: It is recommended to implement preemptive
analgesia during the preoperative phase (especially multimodal an­
algesia and nonsteroidal anti-inflammatory drugs) to reduce opioid
consumption (low-quality evidence, weak recommendation).
Evidence summary: A 2022 network meta-analysis (188 RCTs,
n = 13,769)61 showed that 19 types of preoperative preemptive an­
algesic drugs and interventions—including acetaminophen and NSAIDs,
opioids, NMDA receptor antagonists, and α2-adrenergic receptor ago­
nists (five drug types), as well as multimodal analgesia, epidural an­
algesia, incision infiltration, and acupuncture (four intervention mea­
sures)—were compared with placebo. Among them, 10 reduced
postoperative pain scores, 8 reduced cumulative postoperative opioid
consumption, 5 prolonged the time to first postoperative rescue an­
algesia, and 5 reduced the incidence of postoperative nausea and vo­
miting.
Based on the previous network meta-analysis, the evidence group
conducted an updated review (1111 RCTs; 434 in English and 677 in
Chinese), analyzing 27 preoperative preventive analgesic drugs and
interventions. The update included two additional drug categories corticosteroids and local anesthetics represented by lidocaine - and two
additional interventions - nerve block and intrathecal injection - and
replaced “acupuncture” with “nerve/acupoint stimulation”. Seven out­
comes were assessed: static pain score at 6–48 h postoperatively and
cumulative opioid consumption (oral morphine equivalent dose) at
12–48 h postoperatively. Compared with placebo, 21 of the 27 inter­
ventions reduced postoperative pain scores, and 19 reduced cumulative
opioid consumption (oral morphine equivalent dose). Among the top
five analgesic drugs or interventions for each outcome, the most fre­
quently identified were: combination of two or more drugs/
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multimodal analgesia",74 emphasizing personalized analgesia tailored
to pain sources, surgical site, trauma severity, and functional re­
habilitation needs, providing an essential direction for the development
of multimodal analgesia.
Clinical question 6: what are the advantages of multimodal analgesia in
postoperative pain management?
Recommendation 8: It is recommended to use multimodal an­
algesia during the perioperative period to improve postoperative an­
algesic outcomes and reduce opioid consumption (low-quality evi­
dence, strong recommendation), reduce the incidence of nausea and
vomiting, improve recovery quality and patient satisfaction (moderatequality evidence, weak recommendation), reduce postoperative seda­
tion levels, and shorten hospital stay (high-quality evidence, strong
recommendation).
Evidence summary: A systematic review conducted by the evi­
dence group (110 RCTs, n = 6576) included multimodal analgesia
across various surgical types. The results showed that for postoperative
pain scores (110 RCTs, n = 6576), compared with single-mode an­
algesia, multimodal analgesia reduced postoperative pain scores (VAS
or NRS) (SMD −1.34; 95 % CI −1.72 to −0.96). Subgroup analysis
based on different pain scoring systems also showed reductions in VAS
(SMD −1.60; 95 % CI −2.25 to −0.96) and NRS scores (SMD −0.75;
95 % CI (−1.72 to −0.96)). However, there was substantial hetero­
geneity (I² = 95 %).
For postoperative opioid consumption (61 RCTs, n = 5159), multi­
modal analgesia significantly reduced perioperative opioid use (SMD
−1.89; 95 % CI −2.60 to −1.18), including intraoperative (SMD
−2.54; 95 % CI −4.38 to −0.70) and postoperative use (SMD −1.65;
95 % CI −2.37 to −0.93). Heterogeneity remained high (I² = 95 %).
Regarding postoperative nausea (40 RCTs, n = 2876) and vomiting (30
RCTs, n = 2474), multimodal analgesia reduced the incidence of
nausea (relative risk (RR), 0.63; 95 % CI 0.56 to 0.71, I² = 39 %) and
vomiting (RR 0.66; 95 % CI 0.57 to 0.76, I² = 27 %). For postoperative
sedation levels (17 RCTs, n = 1076), multimodal analgesia reduced
Ramsay sedation scores (SMD −0.18; 95 % CI −0.36 to −0.01), with
moderate heterogeneity (I² = 55 %). Regarding cognitive function (5
RCTs, n = 760), multimodal analgesia improved postoperative MiniMental State Examination (MMSE) scores (SMD 0.46; 95 % CI 0.31 to
0.61), but heterogeneity was high (I² = 96 %). In terms of quality of
recovery (6 RCTs, n = 495), multimodal analgesia significantly im­
proved quality of recovery (QoR) scores compared to single-mode an­
algesia (SMD 0.96; 95 % CI 0.44 to 1.49), with high heterogeneity (I² =
88 %). Regarding hospital stay (17 RCTs, n = 1076), multimodal an­
algesia shortened the average length of stay (SMD −0.15; 95 % CI
−0.27 to −0.03), with moderate heterogeneity (I² = 55 %). For pa­
tient satisfaction (10 RCTs, n = 605), patients receiving multimodal
analgesia reported higher satisfaction during hospitalization (SMD
0.43; 95 % CI 0.03 to 0.83), although heterogeneity was high (I² =
80 %).
Rationale for recommendation: Multimodal analgesia emphasizes
the combination of two or more analgesic drugs or techniques with
different mechanisms of action (including non-opioid analgesics,
opioids, regional blockade, incision site infiltration, etc.).1 Targeting
different sites in the pain transmission pathway can produce synergistic
or additive analgesic effects, reduce the dosage and side effects of single
analgesics,71 facilitate early mobilization and functional rehabilitation,
and accelerate postoperative recovery.72 Therefore, both domestic and
international guidelines and expert consensus encourage the adoption
of multimodal analgesia strategies during the perioperative
period.1,11–13 The systematic review conducted by the evidence group
clarified the advantages of multimodal analgesia in terms of analgesic
efficacy, opioid consumption, postoperative adverse events, recovery
quality, and hospital stay. However, due to the high heterogeneity
among studies and the multifactorial nature of postoperative cognitive
function,73 the expert panel did not reach a consensus on this outcome,
and high-quality research is still needed in the future. According to the
mechanisms of perioperative pain, postoperative pain can be divided
into somatic pain, visceral pain, inflammatory pain, and neuropathic
pain. In 2024, domestic scholars proposed the concept of "precision
Clinical question 7: what is the effect of acetaminophen and/or NSAIDs for
postoperative pain management?
Recommendation 9: For patients without contraindications, it is
recommended to use acetaminophen (moderate-quality evidence,
strong recommendation) and NSAIDs (low-quality evidence, strong re­
commendation) as the foundation for postoperative analgesia to im­
prove pain control and reduce opioid consumption.
Recommendation 10: For patients without contraindications,
combined use of acetaminophen and NSAIDs is recommended, as it
provides superior analgesic efficacy compared to monotherapy (mod­
erate-quality evidence, weak recommendation).
Evidence summary: Acetaminophen as a foundational analgesic for
postoperative pain has been recommended in previous guidelines.1,11 In
recent years, the number of related clinical studies has been limited,
preventing updated evidence synthesis. However, the latest available
research does not substantially alter previous conclusions. Based on
careful evaluation, the evidence group adopted prior systematic re­
views to support the current recommendation for acetaminophen. A
2011 systematic review (11 RCTs, n = 1760; surgeries included or­
thopedic, obstetric and gynecologic, otolaryngologic, oral, cardiovas­
cular, transplant, or mixed types)75 found that intravenous acet­
aminophen (n = 712) significantly increased the proportion of patients
achieving ≥ 50 % pain relief within 4 h (OR 17.22; 95 % CI 5.58 to
53.17) and 6 h (OR 22.00; 95 % CI 5.3 to 91.2) compared with placebo
(n = 1048), reduced the rate of rescue analgesia (OR 0.12; 95 % CI 0.15
to 0.30), prolonged time to first rescue (MD 56 min; 95 % CI 30.2 to
81.8); decreased opioid consumption (morphine equivalent dose)
within 4 h (MD −1.2 mg; 95 % CI −1.6 to −0.8) and 6 h (MD
−2.0 mg; 95 % CI −2.6 to −1.4), with no significant difference in the
incidence of overall adverse events (OR 1.1; 95 % CI 0.8 to 1.7). A 2018
systematic review of abdominal surgery (including laparoscopic and
open approaches)76 (17 studies, n = 1595; 12 RCTs and 5 prospective
cohorts) showed no significant differences in postoperative 12-h pain
scores (MD −0.25 points; 95 % CI −0.59 to 0.08), postoperative 24-h
pain scores (MD −0.10 points; 95 % CI −0.33 to 0.14), or post­
operative 24 h analgesic consumption (morphine equivalent dose) (MD
−3.93 mg; 95 % CI −9.12 to 1.25) between intravenous acet­
aminophen and other comparators (NSAIDs/opioids/local anesthetics).
Subgroup analysis revealed reduced postoperative 24 h analgesic con­
sumption (morphine equivalent dose) in open surgeries (MD −7.29 mg;
95 % CI −13.41 to −1.16). A 2008 systematic review (51 studies,
n = 5762; 50 RCTs, 1 meta-analysis)77 found that at standard doses,
46 % of patients receiving single-dose oral acetaminophen (n = 3277)
achieved ≥ 50 % pain relief within 4–6 h compared to 20 % in the
placebo group (n = 2485) (RR 2.42; 95 % CI 2.21 to 2.64). Number
needed to treat (NNT) for ≥ 50 % pain relief within 4–6 h was: 500 mg,
NNT 3.5 (2.7–4.8); 600–650 mg, NNT 4.6 (3.9–5.5); 975–1000 mg,
NNT 3.6 (3.4–4.0). Approximately 50 % in the acetaminophen group
required rescue within 4–6 h, versus 70 % in the placebo group (RR
0.74; 95 % CI 0.71 to 0.78), with no significant difference in overall
adverse events (RR 1.12; 95 % CI 0.97 to 1.29). Subgroup analysis
showed better pain relief with 975–1000 mg acetaminophen (RR 1.70;
95 % CI 1.49 to 1.95), with no difference in adverse events (RR 1.10;
95 % CI 0.93 to 1.32). A 2022 systematic review comparing intravenous
vs. oral acetaminophen (10 RCTs, n = 1149)78 showed no significant
differences in pain scores (SMD −0.13; 95 % CI −0.36 to 0.11) or
nausea/vomiting incidence (OR 0.89; 95 % CI 0.64 to 1.25).
For NSAIDs in postoperative analgesia, a 2022 systematic review
(27 RCTs, n = 2840; orthopedic surgeries)79 showed parecoxib reduced
resting pain scores at 6 h (MD −0.87 points; 95 % CI −1.71 to −0.03),
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12 h (MD −0.86 points; 95 % CI −1.26 to −0.46), 24 h (MD −0.57
points; 95 % CI −0.80 to −0.31), and 48 h (MD −0.40 points; 95 % CI
−0.69 to −0.11), and movement pain scores at 24 h (MD −0.66
points; 95 % CI −1.14 to −0.19) and 48 h (MD −0.78 points; 95 % CI
−1.16 to −0.39). Parecoxib also reduced 24 h morphine use (MD
−11.30 mg; 95 % CI −14.79 to −7.81) and rescue analgesia (RR 0.83;
95 % CI 0.77 to 0.89), with no significant difference in adverse events
(RR 0.95; 95 % CI 0.86 to 1.04). A 2022 systematic review of TKA/THA
patients (11 RCTs, n = 1911)80 found parecoxib reduced resting pain at
12 h (SMD −0.87; 95 % CI −1.66 to −0.08), 24 h (SMD −0.57; 95 %
CI −1.19 to −0.04), 48 h (SMD −0.38; 95 % CI −0.74 to −0.02), and
movement pain at 12 h (SMD −0.89; 95 % CI −1.83 to 0.06), 24 h
(SMD −0.89; 95 % CI −1.83 to −0.06), 48 h (SMD −0.77; 95 % CI
−1.52 to −0.03), with no significant difference in adverse events (RR
0.82; 95 % CI 0.66 to 1.04). A 2021 systematic review (1 RCT, n = 201;
bunion surgery)81 showed ibuprofen improved ≥ 50 % pain relief at
4–6 h postoperatively (RR 1.44; 95 % CI 0.77 to 2.66), with no sig­
nificant difference in adverse events (RR 0.98; 95 % CI 0.81 to 1.19). A
2022 systematic review (7 RCTs; third molar extraction)82 found cel­
ecoxib 400 mg reduced rescue analgesia (OR 0.31; 95 % CI 0.17 to
0.56), and reduced nausea (OR 0.54; 95 % CI 0.32 to 0.92) and vo­
miting (OR 0.44; 95 % CI 0.22 to 0.90) compared to ibuprofen 400 mg.
For combined acetaminophen and NSAIDs, a 2021 systematic re­
view of oral surgery (7 RCTs, n = 2947)83 compared fixed-dose com­
binations (FDCs) of acetaminophen and ibuprofen to monotherapy or
placebo. Three FDCs were studied: low-dose (75 −100 mg ibuprofen/
250 mg acetaminophen), medium-dose (150 −200 mg ibuprofen/
500 mg
acetaminophen,
FDA-approved),
and
high-dose
(292.5 −400 mg ibuprofen/975 −1000 mg acetaminophen). FDCs sig­
nificantly increased ≥ 50 % pain relief (RR 2.60; 95 % CI 2.11 to 3.20),
and reduced need for rescue medication (RR 0.51; 95 % CI 0.37 to
0.71), with no increase in overall adverse events (RR 0.93; 95 % CI 0.73
to 1.20), serious events (RR 0.82; 95 % CI 0.44 to 1.50), or treatmentrelated events (RR 0.83; 95 % CI 0.50 to 1.39). It also reduced headache
(RR 0.43; 95 % CI 0.25 to 0.75) and nausea (RR 0.47; 95 % CI 0.30 to
0.73). Subgroup analysis showed that medium/low-dose FDCs sig­
nificantly increased ≥ 50 % pain relief (RR 2.94; 95 % CI 1.85 to 4.68)
compared to monotherapy/placebo. Notably, this study examined
fixed-dose combinations in a single tablet, rather than the combination
of separate marketed drugs, so further research is needed. A 2010
systematic review (21 RCTs, n = 1909; surgeries included dental, or­
thopedic, gynecological, general)84 found that acetaminophen
+ NSAIDs were superior to either alone in 85 % (vs. acetaminophen)
and 64 % (vs. NSAIDs) of the studies. Compared with acetaminophen
alone, the combination reduced pain by 35.0 % ± 10.9 % and rescue
analgesia by 38.8 % ± 13.1 %. Compared with NSAIDs alone, pain was
reduced by 37.7 % ± 26.6 % and rescue analgesia by 31.3 % ± 13.4 %.
Patient Values and Preferences: Regarding acetaminophen for
postoperative acute pain, 3 patients considered it very important, 1
fairly important, and 1 uncertain. For NSAIDs, 2 considered it very
important, 2 fairly important, and 1 uncertain. For combination
therapy, 2 considered it very important, 2 fairly important, and 1 un­
certain.
Rationale for recommendation: Acetaminophen and NSAIDs are
commonly used non-opioid analgesics in postoperative pain manage­
ment.1 Based on current evidence, acetaminophen, NSAIDs, and their
combination can all improve postoperative analgesic outcomes. As
acetaminophen and NSAIDs work via different mechanisms, their
combined use may enhance analgesic efficacy through synergistic ef­
fects,85 producing better pain relief than monotherapy.84 The 2022
Guideline for the management of acute perioperative pain12 also re­
commends acetaminophen and NSAIDs as first-line medications for
treating pain of various intensities, administered regularly in the ab­
sence of contraindications. The analgesic effects of oral and intravenous
acetaminophen are considered equivalent.78 Selective COX-2 inhibitors
have shown superior analgesic efficacy and lower incidence of
postoperative nausea and vomiting compared to non-selective
NSAIDs,82 However, current evidence is limited to dental surgeries.
Future high-quality studies are needed across a broader range of sur­
gical procedures to compare the analgesic efficacy of different types of
NSAIDs. In addition, although short-term perioperative use of NSAIDs
(not exceeding 7 days) has not been shown to increase the risk of ser­
ious adverse events, including renal impairment, bleeding, impaired
bone or tissue healing, gastrointestinal complications, or cardiac
events,86,87 clinicians should still weigh the risks and benefits when
prescribing NSAIDs. Special caution or avoidance is advised in high-risk
populations such as those with a history of gastrointestinal ulcer
bleeding, hematologic disorders, hepatic or renal disease, severe car­
diac disease, or those undergoing coronary artery bypass graft sur­
gery.88,89
Clinical question 8: what is the effectiveness of peripheral nerve blocks
(PNBs) for postoperative pain management?
Recommendation 11: Peripheral nerve blocks are recommended as
an essential component of multimodal analgesia to improve post­
operative pain control, reduce opioid consumption, and lower the in­
cidence of nausea and vomiting (moderate-quality evidence, strong
recommendation).
Evidence summary: In limb surgeries, a 2021 systematic review on
acute pain after shoulder arthroscopy90 included 40 RCTs，The review
found that, compared with general anesthesia without nerve block,
patients receiving interscalene block had significantly lower VAS pain
scores in the PACU (MD 3.86 points; 95 % CI 2.33 to 5.38), at 2 h (MD
2.70 points; 95 % CI 1.17 to 4.22), 6 h (MD 2.15 points; 95 % CI 1.56 to
2.74), 12 h (MD 1.24 points; 95 % CI 0.18 to 2.31), and 24 h (MD 1.50
points; 95 % CI 0.78 to 2.22) postoperatively, along with increased
opioid consumption (morphine equivalent dose) (MD 15.57 mg; 95 %
CI 6.79 to 24.35). Compared with single-shot interscalene, supraclavi­
cular, and suprascapular nerve blocks, continuous interscalene block
showed lower pain scores at most time points, though differences were
not statistically significant. A 2022 systematic review91 comparing
PNBs in total knee arthroplasty (TKA) included 14 single-shot femoral
nerve block studies, 7 continuous femoral nerve block studies, 6 singleshot adductor canal block studies, and 4 continuous adductor canal
block studies. All four types of nerve blocks reduced postoperative pain
and opioid consumption compared to placebo. Due to significant het­
erogeneity, no pooled meta-analyses were reported for postoperative
pain or opioid consumption in femoral nerve block studies. Compared
with placebo, both single-shot (SMD 0.46; 95 % CI 0.78 to 0.13) and
continuous adductor canal blocks (SMD −0.54; 95 % CI ‐0.81 to 0.27)
significantly reduced opioid consumption. Additionally, single-shot fe­
moral blocks reduced PONV (RR 0.64; 95 % CI 0.49 to 0.84). A 2023
review92 comparing single-shot versus continuous adductor canal
blocks in TKA (11 RCTs, n = 1185) found no significant differences in
pain scores within 48 h (SMD 2.18; 95 % CI −2.34 to 6.74) or opioid
use (SMD 0.28; 95 % CI −0.47 to 1.03), but fewer complications were
reported with single-shot blocks (OR 0.24; 95 % CI 0.14 to 0.41).
In thoracic surgery, a 2020 systematic review93 showed that erector
spinae plane block (ESPB) significantly reduced 24-h opioid use in
thoracic surgery patients (6 studies, n = 385) (MD −10.5 points; 95 %
CI −16.49 to −3.81), resting pain scores at 0–2 h (7 RCTs, n = 404)
(MD −1.84 points; 95 % CI −2.49 to −1.20), 4–6 h (7 RCTs, n = 404)
(MD −1.41 points; 95 % CI −2.11 to −0.70), 8 h (3 RCTs, n = 114)
(MD −1.48 points; 95 % CI −2.43 to −0.53), 24 h (7 RCTs, n = 364)
(MD −0.65 points; 95 % CI −1.19 to −0.11), and 0 −2 h (4 RCTs,
n = 254) (MD −2.75 points; 95 % CI −3.66 to −1.83), 4–6 h (4 RCTs,
n = 254) (MD −2.09 points; 95 % CI −2.80 to −1.37), 8 h (3 RCTs,
n = 114) (MD −1.36 points; 95 % CI −2.05 to −0.68), and 24 h (4
RCTs, n = 254) (MD −1.11 points; 95 % CI −1.85 to −0.37) for
movement pain at corresponding time points. ESPB also reduced PONV
incidence (OR 0.48; 95 % CI 0.27 to 0.86).
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In abdominal surgery, a 2024 meta-analysis94 offers a panoramic
comparison of regional versus systemic analgesia across four common
laparoscopic procedures: cholecystectomy (42 RCTs), bariatric surgery
(13 RCTs), hernia repair (8 RCTs), and appendectomy (4 RCTs). The
authors meticulously catalogued a spectrum of peripheral nerve block
(PNB) techniques—transversus abdominis plane block (28 RCTs),
paravertebral block (3 RCTs), erector spinae plane block (5 RCTs),
rectus sheath block (2 RCTs), quadratus lumborum block (1 RCT), in­
tercostal nerve block (1 RCT), and phrenic nerve block (1 RCT). The
study found that, relative to no PNB, any form of PNB modestly lowered
resting pain scores at 24 h (49 studies, n = 2795, MD −0.72 points;
95 % CI −0.91 to −0.54) and movement pain scores (18 studies,
n = 1083, MD −0.80 points; 95 % CI −1.17 to −0.42), though with no
clinical significance. Delving deeper, a subgroup analysis uncovered an
instructive exception: among patients undergoing hernia repair, PNB
conferred no detectable reduction in 24-h resting pain score (MD −0.08
points; 95 % CI −0.32 to 0.17). At 2 h after surgery, PNBs produced
clinically meaningful decreases in both resting (23 studies, n = 641,
MD −1.23 points; 95 % CI −1.57 to −0.89) and movement pain scores
(10 studies, n = 307, MD −1.38 points; 95 % CI −2.08 to −0.68). The
2024 systematic review,95 comparing subcostal TAP (sTAP) with
wound infiltration (WI) after laparoscopic cholecystectomy (6 RCTs,
n = 314), found consistently lower pain scores with sTAP at 2 h (MD
−0.70 points; 95 % CI −1.28 to −0.12), 6 h (MD −0.89 points; 95 %
CI −1.52 to −0.25), 12 h (MD −0.99 points; 95 % CI −1.54 to
−0.44), and 24 h (MD −0.73 points; 95 % CI −1.16 to −0.29), ac­
companied by a substantial reduction in 24-h opioid consumption
(morphine equivalent dose) (MD −6.67 mg; 95 % CI −9.39 to −3.95).
Importantly, the incidence of PONV remained comparable between
groups (OR 0.58; 95 % CI 0.23 to 1.44). Complementing these findings,
a concurrent 2024 review96 centered on abdominal oncologic surgery
corroborates the analgesic value of PNBs. Aggregating 24 RCTs
(n = 1604), the authors found that PNBs trimmed 24-h resting pain
scores (MD −0.75 points; 95 % CI −1.20 to −0.31) and movement
pain scores (17 RCTs, n = 180, MD −0.93 points; 95 % CI −1.34 to
−0.53) were not clinically significant. At 2 h after surgery, reductions
in both resting (11 RCTs, n = 712, MD −1.87 points; 95 % CI −2.44 to
−1.29) and movement pain scores ((9 RCTs, n = 572, MD −1.79
points; 95 % CI −2.24 to −1.34) were not only statistically robust but
also clinically meaningful. Beyond pain control, PNBs also curtailed
oral morphine requirements on postoperative day 1 (14 RCTs, n = 794,
MD −36.83 mg; 95 % CI −46.10 to −27.56), and attenuated nausea
(12 RCTs, n = 651, RR 0.55; 95 % CI 0.40–0.76), vomiting (11 RCTs,
n = 611, RR 0.55; 95 % CI 0.32 to 0.97), and the composite endpoint of
PONV (9 RCTs, n = 753, RR 0.52; 95 % CI 0.33 to 0.83).
In spine surgery, a 2023 systematic review97 of thoracolumbar fas­
cial plane blocks (17 RCTs, n = 1205) showed significant reductions in
resting pain scores at 2 h (MD −1.78 points; 95 % CI −2.66 to −0.89),
8 h (MD −1.28 points; 95 % CI −1.76 to −0.81), 12 h (MD (95 %
−1.15 points; 95 % CI −1.58 to −0.72), and 24 h (MD −0.82 points;
95 % CI −1.15 to −0.50), along with reduced total analgesic use (SMD
−2.96; 95 % CI −3.88 to −2.04) and lower PONV (OR 0.39; 95 % CI
0.24 to 0.62). Compared with wound infiltration, thoracolumbar blocks
only reduced pain scores at 8 h (MD −1.92 points; 95 % CI −3.75 to
−0.09) and total analgesic use (SMD −1.29; 95 % CI −2.44 to −0.14).
A 2023 systematic review on erector spinae plane block (ESPB) in spine
surgery98 (19 RCTs, n = 1381) reported reduced 24-h opioid use
(morphine equivalent dose) (13 RCTs, n = 859) (MD −9.81 mg; 95 %
CI −12.64 to −6.97) and lower resting pain scores at multiple post­
operative time points (13 RCTs, n = 2746): 0 h (MD −2.84 points;
95 % CI −3.06 to −2.63), 2 h (MD −1.43 points; 95 % CI −2.23 to
−0.63), 4 h (MD −1.14 points; 95 % CI −2.05 to −0.24), 8 h (MD
−1.90 points; 95 % CI −2.21 to −1.59), 12 h (MD −0.46 points; 95 %
CI −0.75 to −0.18), 24 h (MD −0.59 points; 95 % CI −0.73 to
−0.46), and 48 h (MD −0.30 points; 95 % CI −0.54 to −0.06). ESPB
also reduced movement pain scores at multiple postoperative time
points (7 RCTs, n = 1088): 0 h (MD −2.79 points; 95 % CI −3.20 to
−2.37), 2 h (MD −2.28 points; 95 % CI −2.84 to −1.72), 4 h (MD
−1.62 points; 95 % CI −2.86 to −0.39), 8 h (MD −1.71 points; 95 %
CI −2.90 to −0.53), 12 h (MD −1.07 points; 95 % CI −1.96 to
−0.19), 24 h (MD −0.72 points; 95 % CI −0.95 to −0.49), and 48 h
(MD −1.19 points; 95 % CI −1.64 to −0.73). ESPB also reduced
nausea (7 RCTs, n = 526, RR 0.40; 95 % CI 0.27 to 0.60), vomiting (8
RCTs, n = 586, RR 0.43; 95 % CI 0.26 to 0.71), sedation (3 RCTs,
n = 326, RR 0.28; 95 % CI 0.11 to 0.74), and pruritus (6 RCTs, n = 595,
RR 0.46; 95 % CI 0.27 to 0.77). However, it showed no significant effect
on dizziness (3 RCTs, n = 162, RR 0.61; 95 % CI 0.20 to 1.85).
Rationale for recommendation: The advent of ultrasound-guided
techniques has significantly expanded the clinical adoption of periph­
eral nerve blockade (PNB). The 2016 U.S. Guidelines for postoperative
pain management11 recommended PNBs for selected procedures. The
2017 Chinese Expert Consensus1 also suggested PNB alone or combined
with NSAIDs or opioids as a primary strategy for postoperative an­
algesia in limb and trunk surgeries. Furthermore, the 2022 Interna­
tional Consensus on Anesthesia-Related Outcomes after Surgery
(ICAROS)99 recommended PNBs for hip and knee arthroplasty unless
contraindicated. This guideline reviewed common surgical types and
nerve block techniques. Existing evidence supports that single-shot
PNBs can reduce early postoperative pain scores and analgesic use.
However, single-injection techniques typically last < 24 h,100 and
some patients experience rebound pain upon resolution, which may
impair recovery.101 Prolonging the therapeutic window of local anes­
thetic duration remains a key concern. Liposomal bupivacaine offers
prolonged analgesia up to 72 h,102 and has been shown to reduce opioid
consumption.103–105 Future high-quality trials are needed to evaluate
the impact of different PNB techniques on functional recovery and
define optimal PNB strategies per surgery type. Additionally, anesthe­
siologists should receive appropriate training in PNB techniques and be
capable of managing complications (e.g., local anesthetic systemic
toxicity or persistent nerve injury).13
Clinical question 9: what is the effectiveness of neuraxial analgesia (epidural
or spinal) for postoperative pain management?
Recommendation 12: For thoracic and abdominal surgeries, epi­
dural analgesia provides superior postoperative analgesic effects com­
pared to intravenous analgesia, peripheral nerve blocks, or local in­
filtration. However, attention should be paid to preventing
complications associated with epidural puncture and catheterization
(moderate-quality evidence, weak recommendation).
Recommendation 13: For lower limb surgeries, epidural analgesia
is superior to intravenous analgesia. Still, it shows no clear advantage
over peripheral nerve blocks, and it is associated with a higher in­
cidence of urinary retention and more extended hospital stay (mod­
erate-quality evidence, weak recommendation).
Evidence summary: A systematic review by the evidence group
(185 studies, n = 13,405) compared neuraxial analgesia with other
postoperative analgesia methods based on surgical site. Outcomes in­
cluded average, resting, coughing, and movement pain scores at various
time (PACU, 6 h, 12 h, 24 h, 48 h, 72 h) and adverse events. In thoracic
surgeries (45 studies, n = 3512), compared to those receiving in­
travenous analgesia, patients receiving epidural analgesia had sig­
nificantly lower average pain scores at 12 h (SMD −1.49; 95 % CI
−2.68 to −0.30), 24 h (SMD −1.79; 95 % CI −2.85 to −0.55), and
48 h (SMD −1.94; 95 % CI −3.07 to −0.81); lower resting pain scores
at 6 h (SMD −0.91; 95 % CI −1.59 to −0.23), 12 h (SMD −0.57; 95 %
CI −0.88 to −0.26), 24 h (SMD −0.92; 95 % CI −1.69 to −0.15), and
48 h (SMD −0.80; 95 % CI −1.46 to −0.13); and lower coughing pain
at 24 h (SMD −1.32; 95 % CI −3.44 to −0.79). No significant differ­
ences were found in hospital stay (SMD 0.00; 95 % CI −0.32 to 0.31),
PONV (RR 0.61; 95 % CI 0.3 to 1.25), respiratory depression (RR 0.61;
95 % CI 0.14 to 2.61), or pruritus (RR 2.76; 95 % CI 0.37 to 20.63).
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severe postoperative pain.106 The 2020 Chinese Expert Consensus on
Perioperative Pain Management for Oncology Patients107 recommends
epidural analgesia as a preferred method for open thoracic and ab­
dominal cancer surgeries. With the prevalence of minimally invasive
surgery and the broader adoption of peripheral nerve blocks, the use of
epidural analgesia is gradually declining.108 The 2022 Chinese Guide­
lines for perioperative pain management in total knee arthroplasty109
do not recommend routine neuraxial analgesia in multimodal analgesia
protocols for TKA. This guideline compares epidural analgesia with
other modalities across thoracic, abdominal, and lower limb surgeries,
focusing on pain at various time points and adverse outcomes such as
PONV, respiratory depression, hypotension, urinary retention, and
pruritus. Findings indicate that epidural analgesia offers superior pain
control in thoracic and abdominal surgeries (including open and
minimally invasive), although it is associated with higher rates of
PONV, urinary retention, and pruritus in some settings. Therefore,
epidural analgesia remains an essential component of multimodal an­
algesia strategies for thoracic and abdominal surgeries. However, for
lower limb surgeries, epidural analgesia does not demonstrate clear
advantages over peripheral nerve blocks, and is associated with higher
urinary retention and prolonged hospital stay. Thus, it is not re­
commended as the first-line option in this context.
Local anesthetics and opioids are medications used for neuraxial
analgesia. Their combined administration produces synergistic effects
and a longer duration compared to local anesthetics alone.110 The
comparative effects, safety, and recovery outcomes of different neur­
axial analgesia regimens remain unclear, and high-quality studies are
needed to guide clinical practice. This guideline will be updated as new
evidence emerges.
Compared with peripheral nerve block, epidural analgesia showed
lower average pain at 12 h (SMD −1.49; 95 % CI −2.68 to −0.30),
lower coughing pain at 6 h (SMD −0.72; 95 % CI −1.44 to −0.01), and
lower incidence of headache/dizziness (RR 16.54; 95 % CI 1.88 to
145.82). However, PONV (RR 2.06; 95 % CI 1.15 to 3.70), urinary re­
tention (RR 2.66; 95 % CI 1.27–5.57), and pruritus (RR 6.20; 95 % CI
2.60 to 14.77) were higher, with no significant differences in hospital
stay (SMD −0.04; 95 % CI −0.17 to 0.09) or respiratory depression
(RR 4.85; 95 % CI 0.55 to 42.86). Compared with combined in­
travenous with peripheral nerve block or local infiltration, no sig­
nificant difference was observed in resting pain at 24 h (SMD −0.85;
95 % CI −2.05 to 0.35) or PONV (RR 1.17; 95 % CI 0.31 to 4.43).
In abdominal surgeries (114 studies, n = 8494), compared with
intravenous analgesia, epidural analgesia led to lower average pain
scores at 6 h (SMD −1.64; 95 % CI −2.58 to −0.70), 12 h (SMD
−1.13; 95 % CI −1.79 to −0.46), 24 h (SMD −0.38; 95 % CI −0.68 to
−0.08), and 48 h (SMD −0.68; 95 % CI −1.09 to −0.26), lower
resting pain scores at 6 h (SMD −1.26; 95 % CI −2.25 to −0.28), 24 h
(SMD −1.11; 95 % CI −1.68 to −0.54), and 48 h (SMD −0.51; 95 %
CI −0.84 to −0.18), lower coughing pain scores at 24 h (SMD −0.71;
95 % CI −1.32 to −0.10), 48 h (SMD −0.92; 95 % CI −1.59 to
−0.25), and 72 h (SMD −1.26; 95 % CI −2.52 to −0.01), and lower
movement pain scores at 6 h (SMD −1.45; 95 % CI −2.28 to −0.62),
12 h (SMD −2.29; 95 % CI −4.10 to −0.48), and 24 h (SMD −1.17;
95 % CI −1.80 to −0.55). It also lowered PONV (RR 0.80; 95 % CI 0.65
to 0.99), but increased urinary retention (RR 1.96; 95 % CI 1.40 to
2.76) and pruritus (RR 1.57; 95 % CI 1.28 to 1.93), with no significant
differences in hospital stay (SMD −0.20; 95 % CI −0.49 to 0.10), hy­
potension (RR 0.35; 95 % CI 0.07 to 1.80), respiratory depression(RR
0.57; 95 % CI 0.29 to 1.1), headache/dizziness (RR 0.93; 95 % CI 0.50
to 1.72), or bradycardia(RR 1.11; 95 % CI 0.33 to 3.75). Compared with
peripheral nerve block, epidural analgesia showed lower resting pain at
6 h (SMD −1.22; 95 % CI −2.03 to −0.41), 24 h (SMD −0.61; 95 % CI
−0.97 to −0.25), and 48 h (SMD −0.35; 95 % CI −0.58 to −0.12),
but higher resting pain at 72 h (SMD 0.72; 95 % CI 0.04 to 1.40), and
longer hospital stay (SMD 0.37 day; 95 % CI 0.13 to 0.60). There were
no significant differences in PONV, respiratory depression, urinary re­
tention, and pruritus. Compared with local infiltration, epidural an­
algesia resulted in lower resting pain at 6 h (SMD −1.26; 95 % CI
−2.25 to −0.28) and 12 h (SMD −3.09; 95 % CI −5.21 to −0.96),
with no difference in PONV or hospital stay. Compared with combined
intravenous with peripheral nerve block or local infiltration, epidural
analgesia had lower resting pain at 24 h (SMD −0.75; 95 % CI −1.44 to
−0.05), and lower average pain at 24 h (SMD −0.88; 95 % CI −1.66 to
−0.11) and 48 h (SMD −0.90; 95 % CI −1.78 to −0.03), with no
significant difference in hospital stay or adverse events.
In lower limb surgeries (26 studies, n = 1399), epidural analgesia
resulted in lower average pain at 6 h (SMD −0.90; 95 % CI −1.78 to
−0.03) and 12 h (SMD −0.88; 95 % CI −1.66 to −0.11) compared to
intravenous analgesia, but PONV (RR 0.80; 95 % CI 0.55 to 1.15) and
respiratory depression (RR 1.00; 95 % CI 0.42 to 41.22) showed no
significant difference. Compared to peripheral nerve block, epidural
analgesia lowered 12-h pain scores (SMD −2.49; 95 % CI −4.86 to
−0.12) but increased 24-h pain scores (SMD 2.47; 95 % CI 0.14 to
4.80), with no difference at other time. Pruritus (RR 2.63; 95 % CI 0.25
to 28.15) and dizziness/headache (RR 2.79; 95 % CI 0.64 to 12.21)
incidence were similar. However, epidural analgesia was associated
with a longer hospital stay (SMD 1.73; 95 % CI 0.17 to 3.29) and a
higher incidence of urinary retention (RR 2.42; 95 % CI 1.11 to 5.28).
Compared with local infiltration, no significant difference was observed
in PONV (RR 1.93; 95 % CI 0.19 to 19.49).
Rationale for recommendation: Neuraxial analgesia includes
epidural and intrathecal analgesia. Few studies have examined in­
trathecal use in the postoperative period, so this recommendation fo­
cuses on epidural analgesia. Epidural analgesia involves administering
local anesthetics or opioids into the epidural space to treat moderate to
Clinical question 10: how should drugs be appropriately selected for use in
intravenous patient-controlled analgesia (IV-PCA) pumps?
Recommendation 14: It is recommended to combine medications
with different mechanisms of action in IV-PCA pumps to improve an­
algesic efficacy and reduce side effects (very low-quality evidence,
weak recommendation).
Recommendation 15: It is recommended to include µ-opioid re­
ceptor agonists in the formulation of postoperative IV-PCA (very lowquality evidence, weak recommendation).
Recommendation 16: It is recommended to use dexmedetomidine
as an adjuvant drug in postoperative IV-PCA formulations (very lowquality evidence, weak recommendation).
Evidence summary: The guideline working group conducted a
comprehensive search of literature related to IV-PCA formulations,
excluding rarely used drugs or combinations. A total of 528 studies
(n = 45,893) were included. Based on pharmacological mechanisms,
commonly used IV-PCA drugs and their formulations were categorized
into: 1. Opioids: (1) µ-opioid receptor agonists (including µ/κ dual
agonists) and their combinations; (2) Opioid agonist-antagonists and
their combinations；2. Non-opioid centrally acting analgesics and their
combinations；3. NMDA receptor antagonists and their combinations.
In the network meta‑analysis performed by the evidence group, su­
fentanil was set as the common comparator due to its widespread
clinical use and robust evidence support. Using this uniform com­
parator helped to minimize heterogeneity arising from different anes­
thetic regimens. We compared each drug category against sufentanil in
terms of postoperative 24-h and 48-h resting and movement VAS scores
and PONV incidence. Then we used SUCRA (surface under the cumu­
lative ranking curve) values to rank analgesic efficacy and PONV rates,
summarizing the drugs and formulations most frequently appearing in
the top five rankings and, considering of clinical feasibility (such as
drug availability and cost), we proposed priority recommendations.
Results showed that for postoperative 24-h resting VAS scores,
among µ‑receptor agonists and their combinations versus other for­
mulations (468 RCTs, n = 40,642), the top five in descending analgesic
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
ranking were oxycodone + dexmedetomidine (MD −0.89 points; 95 %
CI −1.61 to −0.17), sufentanil + ketamine (MD −0.84 points; 95 % CI
−0.95 to −0.72), sufentanil + nalbuphine (MD −0.63 points; 95 % CI
−0.75 to −0.51), oxycodone + ketorolac (MD −0.82 points; 95 % CI
−1.80 to 0.16), and hydromorphone + flurbiprofen ester (MD −0.75
points; 95 % CI −1.67 to 0.17). Among opioid agonist-antagonists and
their combinations versus other formulations (167 RCTs, n = 15,290),
the top five were butorphanol + ketorolac (MD −1.10 points; 95 % CI
−2.26 to 0.06), sufentanil + morphine (MD −0.81 points; 95 % CI
−1.39 to −0.23), sufentanil + tramadol (MD −0.84 points; 95 % CI
−1.54 to −0.15), sufentanil + dezocine + dexmedetomidine (MD
−0.82 points; 95 % CI −1.61 to −0.03), and butorphanol + dexme­
detomidine (MD −0.72 points; 95 % CI −1.38 to −0.06). Among
non‑opioid central analgesics and their combinations (55 RCTs,
n = 4912), the top five were fentanyl + butorphanol (MD −1.84
points; 95 % CI −3.36 to −0.32), sufentanil + tramadol (MD −0.81
points; 95 % CI −1.90 to 0.34), sufentanil alone (MD −0.55 points;
95 % CI −1.72 to 0.63), fentanyl + flurbiprofen ester (MD −0.54
points; 95 % CI −1.84 to 0.77), and sufentanil + dezocine (MD −0.51
points; 95 % CI −1.77 to 0.75). Among NMDA receptor antagonists and
their combinations (26 RCTs, n = 2809), the top four were sufentanil
+ esketamine (MD −1.04 points; 95 % CI −1.78 to −0.30), sufentanil
+ ketamine (MD −0.70 points; 95 % CI −1.40 to −0.01), sufentanil
alone (MD −0.60 points; 95 % CI −1.32 to 0.11), and fentanyl + ke­
tamine (MD −0.51 points; 95 % CI −0.86 to −0.16).
For postoperative 24 h movement VAS scores, among µ‑receptor
agonists and their combinations versus other formulations (102 RCTs,
n = 9994), the top five were morphine + dexmedetomidine (MD
−1.71 points; 95 % CI −3.56 to 0.14), tramadol alone (MD −1.26
points; 95 % CI −2.96 to 0.43), sufentanil + ketorolac (MD −1.04
points; 95 % CI −2.48 to 0.41), morphine + ketamine (MD −0.83
points; 95 % CI −2.10 to 0.45), and butorphanol + dexmedetomidine
(MD −0.72 points; 95 % CI −1.83 to 0.39). Among opioid agonistantagonists (24 RCTs, n = 2562), the top five were ketorolac alone (MD
−1.77 points; 95 % CI −2.93 to 0.20), dezocine alone (MD −0.78
points; 95 % CI −1.31 to −0.25), sufentanil + tramadol (MD −0.86
points; 95 % CI −1.91 to −0.15), butorphanol + dexmedetomidine
(MD −0.76 points; 95 % CI −1.22 to −0.30), and esketamine + nal­
buphine (MD −0.54 points; 95 % CI −1.40 to 0.33). Among non‑opioid
centrals (4 RCTs, n = 376), the top four were ketorolac (MD −1.72
points; 95 % CI −3.14 to −0.30), dezocine (MD −1.36 points; 95 % CI
−2.30 to −0.41), tramadol (MD 0.05 points; 95 % CI −0.65 to 0.75),
and fentanyl (MD 1.75 points; 95 % CI 0.25–3.25). Among NMDA an­
tagonists (3 RCTs, n = 360), ketamine + nalbuphine versus nalbuphine
alone showed no significant difference.
For postoperative 48-h resting VAS scores, among µ‑receptor ago­
nists and their combinations (364 RCTs, n = 31,438), the top five were
morphine + dexmedetomidine (MD −1.32 points; 95 % CI −2.25 to
−0.39), sufentanil + nalbuphine (MD −0.65 points; 95 % CI −1.24 to
−0.06), oxycodone + dexmedetomidine (MD −0.51 points; 95 % CI
−1.16 to 0.14), esketamine + nalbuphine (MD −0.65 points; 95 % CI
−1.86 to 0.56), and sufentanil + dezocine + dexmedetomidine (MD
−0.39 points; 95 % CI −1.10 to 0.32). Among opioid agonist-antago­
nists (141 RCTs, n = 12,508), the top five were sufentanil + nalbu­
phine (MD −0.48 points; 95 % CI −1.09 to 0.13), butorphanol + ke­
torolac (MD −0.72 points; 95 % CI −1.90 to 0.47), sufentanil
+ dezocine + dexmedetomidine (MD −0.25 points; 95 % CI −0.99 to
0.48), esketamine + nalbuphine (MD −0.25 points; 95 % CI −1.01 to
0.52), and butorphanol + dexmedetomidine (MD −0.18 points; 95 %
CI −0.84 to 0.47). Among non‑opioid centrals (36 RCTs, n = 3418),
the top four were sufentanil (MD 1.03 points; 95 % CI −0.13 to 2.20),
sufentanil + dezocine (MD 1.09 points; 95 % CI −0.20 to 2.38), su­
fentanil + tramadol (MD 1.19 points; 95 % CI 0.08 to 2.30), sufentanil
+ butorphanol (MD 1.22 points; 95 % CI −0.14 to 2.57). Among
NMDA antagonists (28 RCTs, n = 2417), the top five were sufentanil
+ esketamine (MD −0.59 points; 95 % CI −1.27 to 0.08), sufentanil
+ ketamine (MD −0.42 points; 95 % CI −1.06 to 0.22), sufentanil (MD
−0.23 points; 95 % CI −0.87 to 0.41), morphine + ketamine (MD
−0.13 points; 95 % CI −1.27 to 1.02), fentanyl + ketamine (MD
−0.15 points; 95 % CI −0.55 to 0.26).
For postoperative 48 h movement VAS scores, among µ‑receptor
agonists and their combinations (82 RCTs, n = 7977), the top five were
tramadol (MD −1.97 points; 95 % CI −8.72 to 4.78), fentanyl
+ dexmedetomidine (MD −1.91 points; 95 % CI −8.61 to 4.79),
morphine + dexmedetomidine (MD −1.81 points; 95 % CI −7.58 to
3.96), fentanyl (MD −1.21 points; 95 % CI −6.54 to 4.12), and oxy­
codone + ketorolac (MD −1.42 points; 95 % CI −8.93 to 6.09).
Among opioid agonist-antagonists (25 RCTs, n = 2695), the top five
were sufentanil + dezocine + dexmedetomidine (MD −0.91 points;
95 % CI −2.03 to 0.22), butorphanol + dexmedetomidine (MD −0.70
points; 95 % CI −1.19 to −0.22), sufentanil + dexmedetomidine (MD
−0.44 points; 95 % CI −1.18 to 0.31), nalbuphine + flurbiprofen ester
(MD −0.32 points; 95 % CI −1.35 to 0.70), and dezocine + flurbi­
profen ester (MD −0.24 points; 95 % CI −0.93 to 0.44). Among
non‑opioid centrals (4 RCTs, n = 376), the top four were dezocine (MD
0.51 points; 95 % CI −2.06 to 3.08), ketorolac (MD 0.86 points; 95 %
CI −2.57 to 4.28), tramadol (MD 0.88 points; 95 % CI −1.08 to 2.84),
and fentanyl (MD 1.64 points; 95 % CI −1.87 to 5.15). Compared with
other analgesic strategies, NMDA-receptor antagonists—especially
when used in combination—remain sparsely documented. This paucity
of data precludes the conduct of a robust network meta-analysis and
limits the evidence base available to guide clinical decisions.
For PONV incidence, among µ‑receptor agonists and their combi­
nations (188 RCTs, n = 1749), the lowest rates were tramadol + lor­
noxicam (RR 0.57; 95 % CI 0.07 to 4.76), tramadol alone (RR 0.37;
95 % CI 0.07 to 1.96), hydromorphone + flurbiprofen ester (RR 0.43;
95 % CI 0.06 to 2.99), remifentanil (RR 0.47; 95 % CI, 0.05 to 4.59),
and fentanyl (RR 0.28; 95 % CI 0.06 to 1.29). Among opioid agonistantagonists (58 RCTs, n = 5929), the lowest were morphine (RR 0.39;
95 % CI 0.05 to 3.14), sufentanil (RR 0.22; 95 % CI 0.05 to 0.96),
fentanyl (RR 0.19; 95 % CI 0.04 to 0.88), fentanyl + tramadol (RR 0.31;
95 % CI 0.02 to 4.43), and sufentanil + tramadol (RR 0.19; 95 % CI
0.02 to 1.47). Among non‑opioid centrals (11 RCTs, n = 1358), the
lowest were tramadol (RR 1.41; 95 % CI 0.59 to 3.33), lornoxicam (RR
1.06; 95 % CI 0.26 to 4.42), hydromorphone + flurbiprofen ester (RR
0.85; 95 % CI 0.07 to 10.50), tramadol + lornoxicam (RR 0.80; 95 % CI
0.26 to 2.46), and tramadol + flurbiprofen ester (RR 0.56; 95 % CI 0.08
to 4.11). Among NMDA antagonists (12 RCTs, n = 137), the lowest
were sufentanil + esketamine (RR 0.76; 95 % CI 0.56 to 1.04) and
sufentanil + ketamine (RR 0.39; 95 % CI 0.07 to 2.06).
In the analysis of dexmedetomidine and ketamine/esketamine as
adjuvants (102 RCTs, n = 8920), analgesic efficacy rankings were de­
zocine + dexmedetomidine (MD −0.99 points; 95 % CI −3.08 to
1.10), oxycodone + dexmedetomidine (MD −0.71 points; 95 % CI
−2.81 to 1.39), sufentanil + ketamine (MD −0.46 points; 95 % CI
−1.97 to 1.05), butorphanol + dexmedetomidine (MD −0.50 points;
95 % CI −2.05 to 1.05), and fentanyl + dexmedetomidine (MD −0.18
points; 95 % CI −2.05 to 1.05).
In the 15 drug-class–stratified network meta-analyses, combination
therapy featured in 75 % of the highest-ranked regimens. Among opioid
agonist–antagonists, 40 % of the leading regimens incorporated a µreceptor agonist. This proportion rose to 64.7 % among non-opioid
centrally acting agents and reached 100 % for NMDA-receptor antago­
nists. Among adjuvant analgesics, dexmedetomidine was present in
37.5 % of the top-ranked opioid-containing regimens. Specifically, the
µ-opioid agonist–dexmedetomidine combination ranked within the top
two for every efficacy outcome and accounted for 25 % of all regimens.
Other µ-opioid agonist–based combinations also demonstrated strong
analgesic efficacy, contributing an additional 20 %. In analyses re­
stricted to regimens combining dexmedetomidine with ketamine or
esketamine, dexmedetomidine was a component of 80 % of the highestranked protocols.
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Rationale for recommendation: IV‑PCA allows patients to
self‑administer boluses via a programmed pump according to pain in­
tensity and needs, enabling individualized pain management.111 PCA
offers rapid onset, relatively stable plasma concentrations, and timely
breakthrough pain control, making it a common method for managing
moderate‑to‑severe postoperative pain.1 However, despite the avail­
ability of various PCA formulations that, typically include opioids,
non‑opioid analgesics, and NMDA antagonists, high‑quality evidence on
optimal combinations is lacking. This guideline used 24-h/48-h resting
and movement VAS scores and PONV incidence as outcomes to evaluate
different formulations and recommend the most frequently top‑ranked
drugs and combinations. Combining drugs with different analgesic
mechanisms in IV‑PCA can produce additive or synergistic effects, al­
lowing for lower individual doses and fewer side effects.111 Opioids,
due to their potent analgesic effects, play a central role in moder­
ate‑to‑severe postoperative pain management.108,112 However, their
use is often accompanied by respiratory depression and PONV. Com­
bining dexmedetomidine with opioids can reduce opioid dose, PCA
demands, and rescue analgesia, lower pain scores and PONV, and im­
prove patient satisfaction—though caution or avoidance is required in
patients with bradycardia or conduction block.113 Esketamine as an
IV‑PCA adjuvant can reduce opioid consumption, PONV,114 and post­
operative depression risk.115 However, prolonged infusion of esketa­
mine may increase psychotomimetic effects, necessitating close mon­
itoring.116 New G‑protein‑biased µ‑receptor agonists activate G‑protein
pathways to produce analgesia while reducing β‑arrestin recruitment
and opioid side effects. They have been used recently for moder­
ate‑to‑severe acute postoperative pain.117–119 Compared to traditional
opioids, the biased agonist (tegileridine and oliceridine) provides more
effective IV‑PCA analgesia with a lower incidence of PONV.118–122 In
summary, it is recommended to configure IV‑PCA pumps with drugs of
different mechanisms to enhance analgesia and reduce side effects.
However, current studies have limitations and high heterogeneity, and
future research should further explore optimized PCA formulations to
improve efficacy and safety.
patient satisfaction was significantly higher (MD 1.01 points; 95 % CI
0.56–1.45). Four studies compared recovery quality: one using QoR‑40
showed scores of 184 (171,195) versus 188 (181,195), P = 0.088.
Three studies using QoR‑15 (n = 312) showed no significant difference
(MD −2.17 points; 95 % CI −7.03 to 2.69). Eight studies (n = 814)
found no significant difference in length of stay (MD −0.45 days; 95 %
CI −0.98 to 0.08).
Rationale for recommendation: Opioids exert analgesia by acti­
vating opioid receptors in the central and peripheral nervous systems.
They are commonly used to treat moderate‑to‑severe acute post­
operative pain.1 Still, they carry adverse effects such as postoperative
nausea and vomiting, respiratory depression, and the risk of addiction
and misuse,123 which can hinder early recovery. Therefore, reducing
opioid use is a trend in acute postoperative pain management under the
ERAS concept.124,125] Opioid‑sparing analgesia prioritizes non‑opioid
drugs or techniques, using opioids only when necessary and dis­
continuing them as soon as possible.126 This approach emphasizes the
use of the lowest effective opioid dose for the shortest duration to
achieve the fastest functional recovery while adequately controlling
pain and minimizing opioid side effects. The 2021 Chinese Expert
Consensus on Multimodal, Low‑Opioid Perioperative Analgesia for El­
derly Patients recommends a low‑opioid, multimodal, preemptive, and
individualized analgesic regimen to achieve maximal analgesia,
minimal adverse effects, optimal physical and psychological function,
the best quality of life, and the highest patient satisfaction.127 While
opioid-sparing regimens are widely advocated, current evidence lacks
consensus on their benefits for postoperative recovery quality or hos­
pital stay duration, with numerous studies reporting neutral or negative
outcomes. High‑quality studies are still needed to evaluate their impact
on patient recovery and to implement individualized analgesic plans
that will enhance outcomes.
Clinical question 12: how to prevent and manage common adverse effects
caused by opioids in pain management?
Recommendation 18: It is recommended to closely monitor pa­
tients’ respiratory rate and oxygen saturation to promptly detect po­
tential opioid‑induced respiratory depression (GPS).
Recommendation 19: For patients who develop respiratory de­
pression or excessive sedation, opioid use should be reduced or sus­
pended, the airway kept patent, and consideration should be given to
administering naloxone or nalfurafine. Respiratory support therapy
should be employed if necessary (GPS).
Recommendation 20: In elderly patients, postoperative opioid
dosing should be appropriately reduced to prevent excessive opioi­
d‑induced sedation (GPS).
Recommendation 21: For PONV in low‑ to moderate‑risk patients,
prophylactic use of one or two agents from serotonin 5‑HT₃ receptor
antagonists (high‑quality evidence, strong recommendation), gluco­
corticoids (high‑quality evidence, strong recommendation), dopamine
receptor antagonists (moderate‑quality evidence, strong recommenda­
tion), or neurokinin‑1 receptor antagonists (high‑quality evidence,
strong recommendation) is recommended. For high‑risk patients,
combined use of two to three or more agents is recommended
(high‑quality evidence, strong recommendation).
Evidence summary: Respiratory depression: Clinical studies on the
prevention and management of opioid‑induced respiratory depression
are relatively few, and high heterogeneity precludes evidence synthesis.
The 2020 Shanghai Expert Consensus on Perioperative Pain
Management in General Surgery128 recommends individualized, mul­
timodal analgesia to avoid respiratory depression from opioid overdose.
When respiratory depression occurs, management principles include
suspending opioid analgesics to reduce PCA dosing, maintaining airway
patency, routinely monitoring respiratory rate and pulse oximetry
postoperatively, providing supplemental oxygen and avoiding hypoxia.
For respiratory depression due to opioid overdose or residual effect,
Clinical question 11: what is the impact of opioid‑sparing analgesia on
postoperative recovery?
Recommendation 17: Post-operative analgesia should routinely
incorporate regional blockade and/or systemic non-opioid agents (e.g.
acetaminophen, nonsteroidal anti‑inflammatory drugs, NMDA receptor
antagonists, α2 adrenergic receptor agonists, dexamethasone, lido­
caine) to reduce opioid consumption, mitigate opioid-related adverse
events and improve patient satisfaction (low‑quality evidence, strong
recommendation).
Evidence summary: The evidence group’s systematic review in­
cluded 79 RCTs (n = 7124), in which the intervention arms employed
opioid‑sparing regimens—acetaminophen, NSAIDs, dexmedetomidine,
dexamethasone, ketamine/esketamine, magnesium sulfate, nerve
blocks, local infiltration, etc. The control group used postoperative in­
travenous opioids. Pooled results showed that, compared with controls,
opioid‑sparing regimens reduced resting VAS scores at 6 h (MD −0.62
points; 95 % CI −1.01 to −0.22), 12 h (MD −0.67 points; 95 % CI
−1.04 to −0.30) and 24 h (MD −0.4 points; 95 % CI −0.66 to −0.14),
and reduced movement VAS scores at 6 h (MD −0.87 points; 95 % CI
−1.49 to −0.24), 12 h (MD −0.78 points; 95 % CI −1.2 to −0.37),
24 h (MD −0.49 points; 95 % CI −0.81 to −0.17) and 48 h (MD −0.36
points; 95 % CI −0.61 to −0.11). However, the difference in 48-h
resting VAS scores was not significant (MD −0.09 points; 95 % CI
−0.23 to 0.04). Forty studies (n = 2844) demonstrated reduced post­
operative morphine consumption (MD −9.27 mg; 95 % CI −11.78 to
−6.76). Adverse event rates were lower with opioid‑sparing regimens:
PONV (27 studies, n = 3089; OR 0.64; 95％CI 0.45–0.92), dizziness (16
studies, n = 1724; OR 0.58; 95％CI, 0.37–0.93) and pruritus (10 stu­
dies, n = 750; OR 0.51; 95％CI, 0.31–0.85). In five studies (n = 359),
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intravenous naloxone 5–10 µg/kg may be administered. If respiratory
depression occurs despite non‑excessive epidural opioid dosing, epi­
dural analgesia should be discontinued and catheter position assessed
for possible intrathecal migration. A 2022 meta‑analysis (14 studies,
n = 1071)129 found that nalfurafine was significantly superior to na­
loxone in treating opioid adverse effects, shortening extubation time
(MD −1.58 min; 95 % CI −2.26 to −0.90) and respiratory recovery
time (MD −1.89 min; 95 % CI −3.10 to −0.71), as well as improving
consciousness (eye‑opening time: MD −0.78 min; 95 % CI −1.10 to
−0.46; command response time: MD −0.49 min; 95 % CI −0.80 to
−0.17).
Excessive sedation: The 2017 Expert Consensus on Adult
Postoperative Pain Management1 advises that inability to be aroused or
coma should be treated as excessive sedation, with vigilance for airway
obstruction or respiratory depression.
Nausea and vomiting: A 2021 network meta‑analysis (585 RCTs,
n = 97,516)130 evaluated 44 single agents and 51 combinations for
PONV within 24 h postoperatively. Agents demonstrating significant
efficacy included aprepitant (RR 0.26; 95 % CI 0.18 to 0.38), ramose­
tron (RR 0.44; 95 % CI 0.32 to 0.59), granisetron (RR 0.45; 95 % CI 0.38
to 0.54), dexamethasone (RR 0.51; 95 % CI 0.44 to 0.57), ondansetron
(RR 0.55; 95 % CI 0.51 to 0.60), and droperidol (RR 0.61; 95 % CI 0.54
to 0.69). Combinations of different drug classes were generally more
effective than monotherapy. A 2023 systematic review (12 RCTs,
n = 1276)131 showed dexamethasone reduced PONV incidence (RR
0.50; 95 % CI 0.26 to 0.95). A 2024 systematic review (47 RCTs,
n = 14,435)132 reported that high‑dose dexamethasone (≥0.2 mg/kg
or ≥15 mg) or high‑dose methylprednisolone (≥125 mg) effectively
reduced 24 h PONV (OR 0.29; 95 % CI 0.24 to 0.36). A 2024 network
meta‑analysis (33 RCTs, n = 4238)133 found that 5‑HT₃ antagonists
combined with dexamethasone were more effective than monotherapy
in preventing opioid‑associated PONV after cesarean delivery. A 2023
meta‑analysis on aprepitant (17 RCTs, n = 3299)134 demonstrated that
prophylactic aprepitant significantly reduced PONV (OR 0.34; 95 % CI
0.26 to 0.44), and that aprepitant combined with dexamethasone and
ondansetron further improved outcomes (OR 0.36; 95 % CI 0.16 to
0.82). Although metoclopramide at 25 mg and 50 mg has been shown to
reduce PONV, the efficacy of a 10 mg dose remains controversial.135–137
Rationale for recommendation: Opioid‑induced adverse reactions
commonly include respiratory depression, excessive sedation, nausea
and vomiting, pruritus, dizziness, urinary retention, delirium, cognitive
impairment, and constipation.138,139 The prevention and management
of these opioid‑related adverse events are integral components of pain
management and are fully endorsed in both domestic and international
guidelines and consensus statements. This guideline, based on a com­
prehensive literature review, focuses on the three most frequent post­
operative adverse effects—respiratory depression, excessive sedation,
and nausea/vomiting—and provides specific guidance for their pre­
vention and treatment.
Respiratory depression is defined as respiratory rate ≤ 8 breaths per
minute, arterial oxygen saturation < 90 % on room air, or the onset of
hypopnea.1 Opioid overdose or inappropriate dosing is a key cause of
respiratory depression, and prevention hinges on enhanced monitoring
after opioid administration, with continuous observation of respiratory
rate and oxygen saturation and maintenance of airway patency.140
Antagonists such as naloxone should be administered promptly to re­
verse respiratory depression, with dosing and administration tailored
by the clinician to the severity of the patient’s symptoms.141 Recent
studies suggest that nalfurafine, with higher opioid‑receptor affinity
and longer duration of action, may be superior to naloxone for treating
opioid‑induced respiratory depression.129However, whether nalfurafine
can replace naloxone as the primary opioid antagonist remains con­
troversial.142 There is currently no definitive evidence on how to op­
timize postoperative analgesic regimens to prevent or reduce opioi­
d‑induced respiratory depression, and further high‑quality research is
needed to guide clinical practice.
Excessive sedation is a serious complication of postoperative opioid
analgesia, characterized by reduced consciousness, respiratory depres­
sion, and potentially coma, all of which seriously endanger patient
safety.143–145 Clinical studies on the prevention and management of
opioid‑induced oversedation are similarly scarce. Elderly patients, due
to age‑related declines in physiological function and reduced drug
metabolism and clearance, are particularly susceptible to excessive se­
dation and respiratory depression. Therefore, close postoperative
monitoring is recommended, especially in elderly patients, with vigilant
observation of mental status, respiratory rate, and other vital signs.
Analgesic dosing should start low and be titrated upward to the
minimum effective dose to prevent oversedation.145,146 In cases of es­
tablished oversedation, naloxone may be considered.147–149 However,
the quality of evidence in this area remains low, and further high‑qu­
ality clinical trials are needed.
Nausea and vomiting are among the most common adverse effects of
postoperative opioid use. Employing regional analgesia techniques and
multimodal regimens to minimize opioid consumption can reduce the
incidence of PONV.150 Beyond opioid use, other Apfel risk factors for
PONV include female sex, history of PONV and/or motion sickness, and
nonsmoking status.151 The Fourth Consensus Guidelines 2020 for
management of postoperative nausea and vomiting recommend multi­
modal prophylaxis in patients with one or more risk factors,150 selecting
antiemetics from different pharmacologic classes to target multiple
receptor pathways and optimize efficacy. Serotonin 5‑HT₃ receptor
antagonists, which inhibit 5‑HT₃ receptor activity, reduce central ner­
vous system excitation and alleviate nausea and vomiting,152 making
them first‑line agents for PONV prophylaxis.150 Glucocorticoids such as
dexamethasone decrease the release of inflammatory mediators and
suppress immune cell activity, thereby reducing gastrointestinal mu­
cosal inflammation. Neurokinin‑1 (NK₁) receptor antagonists, such as
aprepitant, bind selectively to central NK₁ receptors, blocking substance
P from initiating the vomiting reflex.153 Dopamine receptor antago­
nists, such as flupentixol and metoclopramide, block D₂ receptors to
inhibit dopaminergic stimulation in the gut, alleviating nausea and
vomiting. Some of these agents also have central antiemetic effects by
modulating gastrointestinal smooth muscle activity.154 Combined an­
tiemetic is more effective than monotherapy and does not result in
additive side effects. If PONV occurs despite prophylaxis, treatment
should be switched to agents of a different pharmacologic class.150
Clinical question 13: what are the risk factors for postoperative breakthrough
pain and rebound pain? How can they be prevented and managed?
Recommendation 22: Orthopedic surgery and preoperative pain
are recommended as risk factors for postoperative rebound pain
(high‑quality evidence, strong recommendation).
Evidence summary: There is currently a lack of evidence identifying
risk factors for postoperative breakthrough pain. For rebound pain, the
guideline evidence group’s systematic review included four studies (two
RCTs, one cohort study, one cross‑sectional study). Meta‑analysis of two
RCTs (n = 223)155,156 showed that orthopedic surgery (OR 6.01; 95 % CI
2.52 to 14.32) and preoperative pain (OR 4.64; 95 % CI 2.75 to 7.81) are
risk factors for rebound pain. A 2021 retrospective cohort study
(n = 993)157 identified younger age (OR 0.98; 95 % CI 0.97 to 0.99),
female sex (OR 1.52; 95 % CI 1.15 to 2.02), orthopedic surgery (OR 1.82;
95 % CI 1.38 to 2.40), and lack of perioperative dexamethasone use (OR
1.78; 95 % CI 1.12 to 2.83) as risk factors for rebound pain. A 2022
cross‑sectional study (n = 384)158 likewise showed preoperative pain
(AOR 3.90; 95 % CI 1.10 to 57.40) and orthopedic surgery (AOR 6.50;
95 % CI 1.45 to 11.70) as risk factors.
Rationale for recommendation: Breakthrough pain is a transient
intensification of pain—spontaneous or triggered by unpredictable
factors—despite relatively stable baseline analgesia and adequate an­
algesic dosing.159 Rebound pain refers to the increase in patient‑re­
ported pain following the resolution of a single‑shot nerve block, often
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
accompanied by increased opioid consumption.160 Identifying risk
factors for breakthrough and rebound pain helps target high‑risk pa­
tients for tailored perioperative analgesia strategies, though clinicians
may confuse these two phenomena. Breakthrough pain typically occurs
with movement, deep breathing, coughing, and rehabilitation ex­
ercises.5 Opioid rescue dosing has been suggested for difficult‑to‑con­
trol breakthrough pain.161,162 However, research on breakthrough pain
and its risk factors remains scarce. Therefore, heightened postoperative
pain assessment and prompt management of breakthrough events are
advised. Rebound pain occurs upon block resolution and is related to
peripheral sensitization.160 Orthopedic surgery often involves greater
tissue trauma and inflammation, and internal fixation hardware can
perpetuate local inflammatory mediator release and nociceptor sensi­
tization,163,164 contributing to rebound pain. Higher preoperative pain
levels also increase peripheral neuroinflammation and sensitization,
predisposing to rebound pain.157,165 Although studies have suggested
catastrophizing, younger age, and female sex are possible risk fac­
tors,160,166 high‑quality evidence linking them specifically to rebound
pain is lacking. So, they are not recommended here. More rigorous
research is needed.
Recommendation 23: In patients without contraindications, acet­
aminophen is recommended to prevent postoperative breakthrough
pain (very low‑quality evidence, weak recommendation).
Recommendation 24: For postoperative breakthrough pain, opioid
rescue dosing is recommended (very low‑quality evidence, weak re­
commendation).
Recommendation 25: In patients at high risk for rebound pain,
intraoperative IV dexamethasone or ketamine/esketamine is re­
commended to prevent postoperative rebound pain (high‑quality evi­
dence, weak recommendation).
Recommendation 26: In patients at high risk for rebound pain,
continuous nerve block or multimodal analgesia is recommended to
prevent postoperative rebound pain (very low‑quality evidence, weak
recommendation).
Evidence summary: For postoperative breakthrough pain, the
evidence group conducted a systematic review based on two RCTs and
one non‑randomized controlled study. A 2018 RCT167 (n = 220)
showed that administering oral acetaminophen between two parenteral
analgesic doses reduced the incidence of breakthrough pain after
elective surgery in adults. A second 2018 RCT168 (n = 55) found that
intravenous acetaminophen and tramadol were equally effective in
treating breakthrough pain following exploratory laparotomy, but the
acetaminophen group experienced a lower rate of postoperative nausea
and vomiting. A 2021 non‑randomized controlled study169 (n = 16)
demonstrated that intranasal fentanyl effectively treated breakthrough
pain provoked by deep breathing and coughing after cardiac surgery.
For postoperative rebound pain, a 2024 meta‑analysis170 (seven
RCTs, n = 574) showed that dexamethasone reduced the odds of re­
bound pain (OR 0.16; 95 % CI 0.10 to 0.27). The evidence group’s
network meta‑analysis (11 RCTs) comparing dexamethasone, ketamine,
and esketamine for preventing rebound pain found that, compared to
no adjuvant, both dexamethasone (OR 0.22, 95 % CI 0.09 to 0.50) and
ketamine/esketamine (OR 0.29; 95 % CI 0.09 to 0.98) significantly
lowered rebound pain incidence. The ketamine/esketamine arm had a
higher—but not statistically different—rebound pain rate than dex­
amethasone (OR 1.36; 95 % CI 0.32 to 5.89). Compared with control,
dexamethasone also significantly reduced PONV (OR 0.33; 95 % CI 0.13
to 0.88), whereas ketamine/esketamine did not (OR 0.86; 95 % CI 0.27
to 2.76). Subgroup analysis showed that intravenous dexamethasone
significantly reduced both rebound pain (OR 0.13; 95 % CI 0.05 to
0.38) and PONV (OR 0.33; 95 % CI 0.13 to 0.83), whereas perineural
dexamethasone did not significantly affect rebound pain (OR 0.38;
95 % CI 0.12 to 1.19) or PONV (OR 0.39; 95 % CI 0.10 to 1.59). Both
intravenous (MD 4.06 h; 95 % CI 1.43 to 6.70) and perineural dex­
amethasone (MD 6.61 h; 95 % CI 3.26 to 9.96) delayed the onset of
rebound pain. Additionally, two 2024 RCTs included in a systematic
review showed that IV magnesium sulfate before shoulder reconstruc­
tion reduced rebound pain [VNRS 4.0 (0.6) vs. 6.2 (0.8), P = 0.03],171
and that, during arthroscopic rotator cuff repair, continuous supracla­
vicular block with IV dexmedetomidine infusion produced a lower re­
bound pain incidence (20 % vs. 56 %, P = 0.001) compared to sin­
gle‑shot block plus dexmedetomidine infusion.172
Rationale: The high frequency of breakthrough pain episodes re­
mains a persistent challenge in acute postoperative pain control. A 2019
study in open gynecologic surgery173 found that 66.8 % of patients
experienced at least one episode of moderate breakthrough pain post­
operatively, 51.4 % had two or more episodes, and 0.6 % experienced
severe breakthrough pain. Breakthrough pain significantly impairs pa­
tients’ quality of life, hinders recovery, and may even precipitate a
range of complications.174 However, clinicians have historically held a
vague concept of breakthrough pain, and related clinical research is
scarce. Breakthrough pain manifests as an acute exacerbation of pain.
Short‑acting opioids, due to their potent effect, rapid onset, brief
duration, and convenient routes of administration, are typically the
first‑line treatment for breakthrough pain.175 The 2022 Australian foot
and ankle surgeons’ consensus on acute postoperative pain manage­
ment also recommends oral opioids for treating breakthrough pain.162
Some studies suggest that acetaminophen can prevent postoperative
breakthrough pain, though the quality of evidence is low, and the
triggers for breakthrough pain are often predictable.169 Therefore,
clinicians should closely monitor patients, regularly assess pain level,
and promptly prevent and manage episodes of breakthrough pain.
Rebound pain is classically defined as the abrupt resurgence of
discomfort once a single-shot peripheral nerve block recedes, with an
incidence of 40–50 %.176,177 This predictable flare not only derails an
otherwise smooth postoperative course but also escalates analgesic re­
quirements, prolongs functional recovery, and saps patient satisfac­
tion.160,178 Recent systematic reviews point to two promising pharma­
cologic allies: intravenous dexamethasone and ketamine (or its
enantiomer esketamine). Dexamethasone attenuates the surgical in­
flammatory cascade, curbs prostaglandin synthesis, and crucially sup­
presses nociceptor priming within dorsal root ganglion, thereby
blunting the sensory “wind-up” that heralds rebond pain.170 Ketamine
and Esketamine, for their part, non-competitively block NMDA re­
ceptors in a voltage‑dependent fashion, limiting calcium influx and
preventing central sensitization.179 Preclinical evidence indicates that
ketamine may affect the mu-opioid receptor pathway both directly, via
weak partial agonism, and indirectly, by facilitating endogenous opioid
release. Pre-clinical data add another layer of nuance: ketamine’s weak
µ-opioid partial agonism and its ability to trigger endogenous opioid
release may synergize with its NMDA antagonism, jointly attenuating
the rebound phenomenon. Beyond these systemic agents, procedural
refinements can further safeguard against rebound. First, extending the
neural blockade itself-via continuous perinural infusion-smooths the
pharmacologic “off-ramp”, allowing nociceptive pathways to downregulate gradually rather than precipitously.160 Second, instituting a
multimodal analgesic regimen before the block wanes sustains an­
algesic continuity during the vlnerable transition period, effectively
bridging the gap until long-acting oral agents reach therapeutic le­
vels.166,180 Together, these approaches weave a seamless analgesic ta­
pestry rather than relying on a single thread. While adjuvants such as
dexamethasone, clonidine, or buprenorphine are increasingly added to
local-anesthetic solutions, trial results remain heterogeneous; definitive
conclusions on optimal dosing and long-term safety await robust, highquality RCTs or pooled analyses.
Clinical question 14: what is the impact of surgery-type-based pain
management strategies on postoperative analgesia?
Recommendation 27: It is recommended to adopt procedur­
e‑specific analgesic regimens to provide individualized pain manage­
ment for patients (low‑quality evidence, strong recommendation).
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
Evidence Summary: Currently, there is no direct clinical evidence on
the implementation of PROSPECT (procedure‑specific postoperative
pain management). A bidirectional cohort study of postoperative an­
algesia after cesarean section (n = 642)181 showed that compared with
traditional multimodal analgesia, a cesarean‑specific analgesic regimen
developed according to recommendations from the PROSPECT working
group (including, but not limited to, standardized transversus abdo­
minis plane blocks and scheduled oral analgesics) reduced the pro­
portion of mothers experiencing moderate‑to‑severe pain (VAS ≥ 7) at
24 h post‑op from 55.5 % to 23.0 % (P < 0.001), and on postoperative
days 2–3 from 35.1 % to 19.1 % (P < 0.001). Analgesia dissatisfaction
rates fell from 8.0 % to 0.7 %, and satisfaction with pain management
services rose from 67.1 % to 90.2 % (P < 0.001).181
Patient Preferences and Values: All five patients surveyed agreed
that procedure‑specific multimodal analgesic regimens for in­
dividualized pain management are very important.
Rationale for recommendation: Different surgical procedures are
associated with varying degrees of postoperative pain,182,183 yet recent
guidelines for postoperative pain management lack optimal strategies
tailored to specific procedures.184,185 The PROSPECT working group’s
website (www.postoppain.org) has published procedure‑specific an­
algesia guidelines covering laparoscopic cholecystectomy, total hip and
knee arthroplasty, abdominal hysterectomy, open cardiac surgery, he­
morrhoidectomy, hernia repair, colectomy, radical prostatectomy, and
others. These guidelines systematically review existing evidence and, in
conjunction with clinical practice, focus on interventions within mul­
timodal analgesia and weigh the risks and benefits of specific techni­
ques for each procedure.186 These guidelines shift the emphasis from
traditional drug‑ and intervention‑centric metrics (e.g., NNT) to pro­
cedure‑specific pain management,13 prioritizing non‑opioid analgesics
and regional techniques, with opioids reserved for rescue. They also
recommend selecting the most effective regional nerve block for each
procedure to optimize postoperative analgesia. Similarly, the 2024 UK
multidisciplinary consensus on adult perioperative pain management
advocates evidence‑based, procedure‑specific, and individualized pain
management strategies.13 However, high‑quality clinical trials are still
needed to verify the advantages of procedure‑specific pain management
in routine practice.
and oral or IV administration of non‑opioid analgesics such as acet­
aminophen and NSAIDs (MD −0.85 points; 95 % CI −1.36 to −0.34)
all reduced pain scores at 1–2 h postoperatively. Additionally, periph­
eral nerve block (MD −1.10 points; 95 % CI −2.18 to −0.02) and
non‑opioid analgesics (MD −1.60 points; 95 % CI −2.51 to −0.68)
also lowered 24-h pain scores.
For severe pain in ambulatory surgery, the evidence group’s me­
ta‑analysis of 61 RCTs found that, compared to control, neuraxial an­
algesia (MD −2.07 points; 95 % CI −3.79 to −0.36), local infiltration
(MD −1.77 points; 95 % CI −3.20 to −0.33), and peripheral nerve
block (MD −1.84 points; 95 % CI −3.37 to −0.31) all reduced pain
scores at 1–2 h postoperatively. Local infiltration (MD −1.25 points;
95 % CI −2.26 to −0.23) and peripheral nerve block (MD −1.27
points; 95 % CI −2.01 to −0.52) also reduced 24-h pain scores.
Rationale for recommendation: Postoperative pain is a leading
cause of delayed discharge and unplanned readmission in day‑case
surgery patients,190,191 making adequate postoperative analgesia a
critical component of perioperative management.187,190 The 2019 UK
Guidelines for day surgery188 categorize pain severity in day‑case pro­
cedures from A (no pain) through B (mild pain), C (moderate pain), to D
(severe pain), with examples of procedures to each grade. Our re­
commendations align with this stratification: for mild pain, multiple
guidelines and consensus statements affirm that acetaminophen and
NSAIDs are sufficient for postoperative analgesia.187–189 For moderate
to severe pain, preoperative oral or periprocedural IV acetaminophen
and/or NSAIDs,192 combined with local infiltration or peripheral nerve
block, can avoid or reduce opioid use and its adverse effects,192 pro­
viding effective analgesia in ambulatory settings.189 New long‑acting
local anesthetics may further optimize postoperative pain control.102
After discharge, patients can continue using acetaminophen or NSAIDs
and, if necessary, opioids can be added. Neuraxial analgesia in day‑case
surgery remains controversial. Although postoperative neuraxial an­
algesia is feasible with catheter retention, early use of anticoagulation
and thromboprophylaxis limits its applicability189 and outpatient
management of neuraxial catheters is challenging. Thus, it is not re­
commended in this guideline.
Clinical question 16: which analgesic regimens are more suitable for
postoperative pain management in elderly patients?
Clinical question 15: which analgesic regimens are more suitable for
postoperative pain management in patients undergoing day surgery?
Recommendation 30: It is recommended to use NSAIDs (low‑qu­
ality evidence, weak recommendation), acetaminophen (low‑quality
evidence, weak recommendation), and peripheral nerve block (very
low‑quality evidence, weak recommendation) for postoperative an­
algesia in elderly patients without contraindications (low‑quality evi­
dence, weak recommendation).
Recommendation 31: Opioid analgesia combined with dexmede­
tomidine is preferable to opioid monotherapy for postoperative pain
control in elderly patients (very low‑quality evidence, weak re­
commendation).
Evidence summary: The guideline evidence group’s systematic
review included 11 RCTs in elderly patients. Three RCTs (n = 829)
evaluated NSAIDs in the postoperative setting193–195 and found that,
compared with placebo, NSAIDs reduced 24-h pain scores (SMD −0.9;
95 % CI −1.6 to −0.1), and lowered the incidence of postoperative
neurocognitive dysfunction (RR 0.6; 95 % CI 0.6 to 0.7). Three RCTs
(n = 294) compared peripheral nerve block with IV opioid PCA in ab­
dominal and lower‑limb surgeries196–198 (n = 294), demonstrating that
both techniques achieved satisfactory analgesia (resting pain < 4
points), with no significant difference in pain scores (SMD −1.1; 95 %
CI −3.0 to 0.8), although the PCA group had a higher rate of PONV
(25.5 % vs. 13.1 %; RR 0.6; 95 % CI 0.3 to 1.0). Four RCTs (n = 1019)
assessed dexmedetomidine as an adjuvant199–202 (n = 1019), finding
that, compared with opioids alone, opioid + dexmedetomidine reduced
pain scores at 6 h (SMD −0.5; 95 % CI −0.9 to −0.1), 24 h (SMD
−0.5; 95 % CI −1.0 to −0.1) and 48 h (SMD −0.7; 95 % CI −1.2 to
Recommendation 28: For ambulatory surgery patients with mild
pain, acetaminophen or nonsteroidal anti‑inflammatory drugs are re­
commended for postoperative analgesia (GPS).
Recommendation 29: For ambulatory surgery patients with mod­
erate to severe pain, it is suggested to use non‑opioid analgesics, such as
acetaminophen and NSAIDs (moderate‑quality evidence, weak re­
commendation), combined with local infiltration (low‑quality evidence,
weak recommendation) or peripheral nerve block (low‑quality evi­
dence, weak recommendation) for postoperative analgesia, adding
opioids if necessary.
Evidence summary: For mild pain in ambulatory surgery, the 2023
Expert Consensus on Enhanced Recovery in Day‑Case Surgery187 states
that oral acetaminophen or NSAIDs are commonly used preventive
analgesic regimens for mild to moderate pain. The 2019 UK Guidelines
for day surgery188 recommend routine prophylactic oral long‑acting
NSAIDs for all patients without contraindications. The 2017 Chinese
Expert Consensus on Adult Day‑Case Postoperative Analgesia189 also
identifies acetaminophen and/or NSAIDs as the basic analgesics for
day‑case surgery, sufficient when used alone for minor to moderate
procedures.
For moderate pain in ambulatory surgery, the evidence group’s
meta‑analysis of 41 RCTs demonstrated that, compared to control,
neuraxial analgesia (MD −1.91 points; 95 % CI −3.46 to −0.36),
peripheral nerve block (MD −1.62 points; 95 % CI −2.38 to −0.85),
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
−0.2), and significantly lowered 48 h PONV incidence (32.4 % vs.
19.4 %; RR 0.4; 95 % CI 0.2 to 0.8). In one small RCT of TKA patients
(n = 36),203 acetaminophen combined with ibuprofen yielded lower
24 h NRS scores (4.8 ± 0.5) than acetaminophen alone (7.3 ± 1.2) or
ibuprofen alone (5.6 ± 0.5) (P < 0.01).
Rationale for recommendation: Elderly patients have diminished
physiologic reserve and organ function, leading to reduced drug toler­
ance and an increased risk of adverse events.127 The 2021 Chinese
Expert Consensus on Multimodal, Low‑Opioid Perioperative Analgesia
for Elderly Patients advocates prioritizing non‑opioid and regional
techniques while minimizing opioid use.127 Our review of elderly (≥ 60
years) postoperative analgesia indicates that acetaminophen and
NSAIDs serve as foundational agents.204,205 However, clinicians must
remain vigilant for cardiovascular, renal, and gastrointestinal side ef­
fects associated with NSAIDs.206 Peripheral nerve blocks offer effective
pain control, reduce opioid requirements, and lower the risk of cogni­
tive dysfunction.206 Age‑related physiologic changes prolong block
duration, necessitating careful attention to local anesthetic concentra­
tion and total dose.205 Opioids may be required for moderate‑to‑severe
pain,207 but dosing should start low and be titrated slowly under close
monitoring to balance analgesia with safety.127 Dexmedetomidine
combined with opioids in IV‑PCA provides synergistic analgesia, re­
duces opioid consumption, and lowers the incidence of PONV.208
However, clinicians must monitor for bradycardia, hypotension, and
over‑sedation.
intensity following tissue injury and persists beyond the normal healing
period, typically lasting longer than three months.213,214 Its incidence
ranges from approximately 10% to 40%.215 Postoperative chronic pain
substantially burdens patients, healthcare systems, and society.5 Studies
have found an association between acute postoperative pain and chronic
postoperative pain.216 Therefore, identifying risk factors for the transi­
tion from acute to chronic pain is crucial for comprehensive risk as­
sessment and the implementation of preventive measures to reduce the
incidence of chronic postoperative pain.217 The transition from acute to
chronic pain is a complex process,218 and research indicates that mul­
tiple factors—patient-related, surgical, and environmental—can con­
tribute to this conversion.215 Among patient factors, age, sex, smoking,
preoperative pain, preoperative anxiety, depression, pain catastro­
phizing, and moderate‑to‑severe postoperative pain are risk factors.
Among surgical factors, longer operative time and wound infection also
increase the risk of chronic postoperative pain. Additionally, geno­
me‑wide association studies (GWAS) have identified B‑lymphocyte-re­
lated genes as closely linked to the transition to chronic pain.219 How­
ever, the impact of surgical type and site, patients’ home environments,
and hospital treatment settings on chronic postoperative pain remains
unclear and requires further research to elucidate.
Recommendation 33: It is recommended to provide transitional
pain services to postoperative patients to prevent acute pain from be­
coming chronic and to reduce long‑term opioid use (low‑quality evi­
dence, weak recommendation).
Evidence summary: A systematic review of three retrospective
cohort studies220: showed that, in organ transplant recipients, transi­
tional pain service (TPS) reduced mean daily morphine use from
9.2 ± 6.3 mg to 7.7 ± 7.3 mg (P < 0.001) and Brief Pain Inventory
scores from 5.6 ± 1.8–4.9 ± 1.2 (P < 0.005). In orthopedic post­
operative, patients managed by TPS versus community care, TPS de­
creased opioid prescribing at 90 days post‑discharge (OR = 0.06, 95 %
CI 0.01–0.48).221 Among opioid‑naïve patients, TPS reduced dis­
charge‑to‑90‑day opioid use by 69.4 %, and by 44.3 % in those with
preoperative opioid use.222 A 2023 RCT of TPS (n = 176)223 found that
TPS recipients had significantly lower opioid consumption at 3 months
(median(M) −30 mg, IQR −60 to 0) and 6 months (median(M)
−29.3 mg, IQR −65.6 to 0).
Rationale: Transitional pain service (TPS), first proposed at
Toronto General Hospital in 2014,224 integrates acute pain service with
postoperative “pain home” follow‑up to provide multidisciplinary peri‑
and post‑discharge pain care.225 A team of anesthesiologists, pain spe­
cialists, nurses, psychologists, and physical therapists delivers multi­
modal analgesia across the preoperative, intraoperative, and post­
operative phases, tapering opioids and optimizing pain
control.223,226,227 Post‑discharge TPS focuses on patient education for
appropriate analgesic use,228 early opioid cessation, and psychological
support to prevent the transition from acute to chronic pain.215,223
Although evidence is still limited, TPS shows promise in reducing
chronic pain development and long‑term opioid reliance. High‑quality
studies are needed to define its role in the future.
Clinical question 17: what are the risk factors for transitioning from acute to
chronic pain? What is the role of transitional pain services in preventing the
development of chronic pain from acute pain?
Recommendation 32: It is recommended to pay attention to the
following risk factors for acute pain converting to chronic pain: mod­
erate‑to‑severe postoperative pain (high‑quality evidence, strong re­
commendation); younger age, female sex, smoking, anxiety, depression,
preoperative pain, longer surgical duration (moderate‑quality evidence,
weak recommendation); postoperative wound infection, pain catastro­
phizing (low‑quality evidence, weak recommendation).
Evidence summary: A 2023 systematic review of chronic
post‑thoracic surgery pain209 included 56 studies and 45 prognostic
factors, 16 of which were meta‑analyzed: preoperative pain (OR 2.86;
95 % CI 1.94 to 4.21); longer operative time (MD 12.02 min; 95 % CI
4.21 to 19.83); and female sex (OR 1.29; 95 % CI 1.04 to 1.60) all sig­
nificantly increased the risk of chronic pain. Intercostal nerve block in­
traoperatively (five observational studies, n = 3959) was protective
against chronic pain (OR 0.76; 95 % CI 0.61 to 0.95). A 2023 review of
total knee arthroplasty210 (30 studies, n = 26,517) analyzed 151 vari­
ables and found younger age increased risk by an absolute 4 % per
decade below age 80 (Absolute Risk Increase (ARI) 4 %; 95 % CI 1.7% to
6.4%). Moderate‑to‑severe acute postoperative pain (ARI 29.5 %; 95 % CI
20.2% to 38.5%), pain catastrophizing (ARI 29.5 %; 95 % CI 11.7% to
34.5%), female sex (ARI 6.7 %; 95 % CI 2.5% to 11.2%), and pre­
operative pain (ARI 35 %; 95 % CI 7.3% to 57.7%) were associated with
persistent pain. A 2022 systematic review in general surgery211 showed
smoking history (five prospective studies, n = 2127; RR 1.69; 95 % CI
1.20 to 2.37) and postoperative wound infection (four retrospective
studies, n = 1885; RR 2.71; 95 % CI 1.74 to 4.18) increased chronic pain
incidence. Another 2022 review in breast surgery patients212 found that
moderate‑to‑severe postoperative pain raised the risk of persistent pain
(RR 1.56; 95 % CI 1.32 to 1.84). Higher state (MD 4.70 points; 95 % CI
2.04 to 7.35) and trait (MD 3.52 points; 95 % CI 2.28 to 4.77) anxiety
scores were linked to chronic pain, and a history of depression increased
risk (RR 1.53; 95 % CI 1.30 to 1.81). Pain catastrophizing elevated
chronic pain risk (MD 3.72 points; 95 % CI 1.08 to 6.35), as did a pre­
operative pain history (RR 1.49; 95 % CI 1.36 to 1.65).
Rationale: Postoperative chronic pain is defined as pain localized to
the surgical area or its related regions that occurs or increases in
Summary and outlook
Postoperative pain management encompasses a wide range of as­
pects. This guideline included 33 recommendations addressing the most
clinically significant issues and, based on these recommendations, de­
veloped a workflow for postoperative management (Fig. 1). Clinicians
are advised to refer to these recommendations in practice and, in
conjunction with individual factors such as patient condition and sur­
gical type, implement standardized postoperative pain management to
reduce pain, decrease perioperative complications, and improve prog­
nosis. However, this guideline also has several limitations. For some
clinical questions, recent research has been limited in number, pre­
cluding evidence synthesis, and new findings have not altered previous
conclusions. After careful evaluation, the evidence group included
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
Fig. 1. Adult postoperative pain-management workflow.
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
systematic reviews older than two years to support the recommenda­
tions, which deviates from the guideline protocol. Additionally, the
heterogeneity among studies included in the systematic reviews for
certain questions was high and the quality of evidence low. Further­
more, this guideline’s assessment of analgesic efficacy focuses primarily
on postoperative pain scores and adverse events, while high‑quality
evidence regarding patient‑centered outcomes, such as functional re­
covery and quality of recovery (QoR), remains lacking.
Precision multimodal analgesia is poised to redefine perioperative
pain care. The pipeline now includes G-protein-biased μ-opioid agonists
such as tegileridine and oliceridine, alongside the peripherally‑selective
κ‑opioid receptor agonists anrikefon-agents that promise potent an­
algesia with markedly fewer systemic adverse effects. Yet, realizing this
potential demands rigorous, well-designed trials that precisely calibrate
dose, timing, and patient phenotype to translate promise into practice.
As this evidence base matures, the guideline panel will regularly update
its recommendations—locking each iteration to the strongest available
science and propelling postoperative pain care toward greater exacting
precision and uniform excellence.
China); Jianjun Yang (Department of Anesthesiology, The First
Affiliated Hospital of Nanjing Medical University, Nanjing, China);
Yaolong Chen (Center for Evidence-Based Medicine, School of Basic
Medical Sciences, Lanzhou University, Lanzhou, China)
Members (in alphabetical order by surname pinyin): Xiaoming Deng
(Department of Anesthesiology, Changhai Hospital, Naval Military
Medical University, Shanghai, China); Yuguang Huang (Department of
Anesthesiology, Peking Union Medical College Hospital, Chinese
Academy of Medical Sciences, Beijing, China); Guolin Wang
(Department of Anesthesiology, Tianjin Medical University General
Hospital, Tianjin, China); Tianlong Wang (Department of
Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing,
China); Lize Xiong (Department of Anesthesiology, Shanghai Fourth
People’s Hospital, Tongji University, Shanghai, China); Jianguo Xu
(Department of Anesthesiology, Eastern Theater General Hospital,
Nanjing, China)
Guideline Consensus Expert Group (in alphabetical order by sur­
name pinyin): Junli Cao (Department of Anesthesiology, The Affiliated
Hospital of Xuzhou Medical University, Xuzhou, China); Xiangdong
Chen (Department of Anesthesiology, Union Hospital, Tongji Medical
College, Huazhong University of Science and Technology, Wuhan,
China); Qinjun Chu (Department of Anesthesiology, Zhengzhou Central
Hospital Affiliated to Zhengzhou University, Zhengzhou, China);
Yugang Diao (Department of Anesthesiology, General Hospital of
Northern Theater Command, Shenyang, China); Yi Feng (Department of
Anesthesiology, Peking University People’s Hospital, Beijing, China);
Shiqing Feng (Orthopedics, Second Hospital of Shandong University,
Weifang, China); Jinhan He (Department of Clinical Pharmacy, West
China Hospital, Sichuan University, Sichuan, China); He Huang
(Department of Anesthesiology, The Second Affiliated Hospital of
Chongqing Medical University, Chongqing, China); Lining Huang
(Department of Anesthesiology, The Second Hospital of Hebei Medical
University, Shijiazhuang, China); Fuhai Ji (Department of
Anesthesiology, The First Affiliated Hospital of Soochow University,
Soochow, China); Xuemei Jia (Department of Gynecology, Affiliated
Maternity Hospital of Nanjing Medical University, Nanjing, China); Jun
Li (Department of Anesthesiology, The Second Affiliated Hospital of
Wenzhou Medical University, Wenzhou, China); Longyun Li
(Department of Anesthesiology, China Japan Union Hospital, Jilin
University, Changchun, China); Xuesheng Liu (Department of
Anesthesiology, The First Affiliated Hospital of Anhui Medical
University, Hefei, China); Ting Liu (Operating Room, Xuanwu Hospital,
Capital Medical University, Beijing, China); Chao Li (Department of
Anesthesiology, Fourth Hospital of Hebei Medical University,
Shijiazhuang, China); Yunshui Peng (Editorial Department of Chinese
Journal of Anesthesiology, The Second Hospital of Hebei Medical
University, Shijiazhuang, China); Jianan Ren (General Surgery, Eastern
Theater General Hospital, Nanjing, China); Shouyuan Tian (Department
of Anesthesiology, Shanxi Provincial People’s Hospital, Taiyuan,
China); Ziqiang Tian (Thoracic Surgery, Fourth Hospital of Hebei
Medical University, Shijiazhuang, China); Dongxin Wang (Department
of Anesthesiology, Peking University First Hospital, Beijing, China); E
Wang (Department of Anesthesiology, Xiangya Hospital, Central South
University, Changsha, China); Yingwei Wang (Department of
Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China);
Fushan Xue (Department of Anesthesiology, Fujian Provincial Hospital,
Fuzhou University, Fuzhou, China); Wenjun Yan (Department of
Anesthesiology, Gansu Provincial People’s Hospital, Lanzhou, China);
Liqiang Yang (Pain Department, Xuanwu Hospital, Capital Medical
University, Beijing, China); Liqun Yang (Department of Anesthesiology,
Renji Hospital, Shanghai Jiao Tong University School of Medicine,
Shanghai, China); Yonghao Yu (Department of Anesthesiology, Tianjin
Medical University General Hospital, Tianjin, China); Jing Zhao
(Department of Anesthesiology, China Japan Friendship Hospital,
Beijing, China); Tao Zhu (Department of Anesthesiology, West China
Hospital, Sichuan University, Sichuan, China)
CRediT authorship contribution statement
Weifeng Yu: Project administration, Writing – review &
editing. Tianlong Wang: Project administration, Writing – review &
editing. Jianjun Yang: Project administration, Writing – review &
editing. Xiangdong Chen: Writing – original draft. Qinjun Chu:
Writing – original draft. Yunshui Peng: Writing – original
draft. Yaolong Chen: Methodology. Alan D. Kaye: Writing – review &
editing. Henry Liu: Writing – review & editing. All authors have read
and agreed to the published version of the manuscript.
Consent for publication
Not applicable.
Ethical statement
Not applicable.
Funding
This research received no external funding.
Data availability
All data cited in this review are publicly available through the ori­
ginal publications listed in the references.
Declaration of competing interest
Xiangdong Chen, Jianjun Yang, Henry Liu (all Editors-in-Chief);
Alan D. Kaye (Associate Editor); Tianlong Wang, Weifeng Yu (both
Advisory Board Members) of Journal of Anesthesia and Translational
Medicine were not involved in the editorial review or the decision to
publish this article. The authors declare that they have no known
competing financial interests or personal relationships that could have
appeared to influence the work reported in this paper. This guideline is
not mandatory and shall not be used as the basis for medical mal­
practice determination or legal responsibility attribution. It is provided
for the reference of relevant healthcare professionals only.
Appendix A
Guideline Steering Committee:
Chairpersons: Weifeng Yu (Department of Anesthesiology, Renji
Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai,
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Journal of Anesthesia and Translational Medicine 4 (2025) 161–185
Guideline Secretariat (Sort by last name pinyin):
Yan Wang (Department of Anesthesiology, Zhengzhou Central
Hospital Affiliated to Zhengzhou University, Zhengzhou, China);
Younian Xu (Department of Anesthesiology, Union Hospital, Tongji
Medical College, Huazhong University of Science and Technology,
Wuhan, China); Yingying Zhao (Department of Anesthesiology, The
First Affiliated Hospital of Zhengzhou University, Zhengzhou, China)
Guideline Methodology Group (in alphabetical order by surname
pinyin, all are anesthesiologists):
Hui Liu (Center for Evidence-Based Medicine, School of Basic
Medical Sciences, Lanzhou University, Lanzhou, China); Tianhu Liang
(Research Center for Clinical Medicine, the First Hospital of Lanzhou
University, Lanzhou, China); Yuxiu Liu (Data and Statistics Office,
Department of Critical Care Medicine, Eastern Theater General
Hospital, Nanjing, China); Zhiguang Ping (School of Public Health,
Zhengzhou University, Zhengzhou, China); Yuanyuan Yao (Center for
Evidence-Based Medicine, School of Basic Medical Sciences, Lanzhou
University, Lanzhou, China); Jie Zhang (Center for Evidence-Based
Medicine, School of Basic Medical Sciences, Lanzhou University,
Lanzhou, China); Junxian Zhao (Research Center for Clinical Medicine,
the First Hospital of Lanzhou University, Lanzhou, China)
Evidence Appraisal Group (in alphabetical order by surname pi­
nyin):
Bing Chen (The Second Affiliated Hospital of Chongqing Medical
University, Chongqing, China); Lu Chen (West China Hospital, Sichuan
University, Sichuan, China); Xi Chen (China-Japan Union Hospital, Jilin
University, Changchun, China); Wei Du (Fourth Hospital of Hebei
Medical University, Shijiazhuang, China); Xixia Feng (West China
Hospital, Sichuan University, Sichuan, China); Lingqi Gao (Huashan
Hospital, Fudan University, Shanghai, China); Suqian Guo (The Second
Hospital of Hebei Medical University, Shijiazhuang, China); Xiaoguang
Guo (The First Affiliated Hospital of Zhengzhou University, Zhengzhou,
China); Jiang Hu (Xiangya Hospital, Central South University,
Changsha, China); Xin Huang (Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China);
Wenwen Huo (The First Affiliated Hospital of Soochow University,
Soochow, China); Yu Jiang (The First Affiliated Hospital of Anhui
Medical University, Hefei, China); Shaowu Jin (The Second Affiliated
Hospital of Wenzhou Medical University, Wenzhou, China); Chao Li
(Shanxi Provincial Peopleʼs Hospital, Taiyuan, China); Ting Li (Gansu
Provincial People’s Hospital, Lanzhou, China); Xia Li (Gansu Provincial
People’s Hospital, Lanzhou, China); Ye Li (The Second Hospital of Hebei
Medical University, Shijiazhuang, China); Zhe Li (China-Japan
Friendship Hospital, Beijing, China); Chang Liu (Xiangya Hospital,
Central South University, Shangsha, China); Huayue Liu (The First
Affiliated Hospital of Soochow University, Soochow, China); Ruizhu Liu
(China-Japan Union Hospital, Jilin University, Changchun, China);
Jiazheng Qi (Huashan Hospital, Fudan University, Shanghai, China);
Hao Qian (Union Hospital, Tongji Medical College, Huazhong
University of Science and Technology, Wuhan, China); Bin Shu (The
Second Affiliated Hospital of Chongqing Medical University,
Chongqing, China); Xuesen Su (Shanxi Provincial Peopleʼs Hospital,
Taiyuan, China); Liang Sun (Peking University People’s Hospital,
Beijing, China); Xiuli Wang (Peking University People’s Hospital,
Beijing, China); Jingjing Wang (Zhengzhou Central Hospital Affiliated
to Zhengzhou University, Zhengzhou, China); Yuanlin Wang (Tianjin
Medical University General Hospital, Tianjin, China); Qingfeng Wei
(The First Affiliated Hospital of Anhui Medical University, Hefei,
China); Yegong Xie (Tianjin Medical University General Hospital,
Tianjin, China); Yun Yan (China-Japan Friendship Hospital, Beijing,
China); Meng Zhang (The General Hospital of Northern Theater
Command, Shenyang, China); Shaoqiong Zhang (The General Hospital
of Northern Theater Command, Shenyang, China); Yue Zhang (The First
Affiliated Hospital of Zhengzhou University, Zhengzhou, China); Zhen
Zhang (Zhengzhou Central Hospital Affiliated to Zhengzhou University,
Zhengzhou, China); Yingfeng Zhou (The Second Affiliated Hospital of
Wenzhou Medical University, Wenzhou, China); Kangsheng Zhu
(Fourth Hospital of Hebei Medical University, Shijiazhuang, China)
External Review Expert Group:
Hailong Dong (Department of Anesthesiology, Xijing Hospital, Air
Force Medical University, Xi'an, China); Bifa Fan (Pain Department,
China-Japan Friendship Hospital, Beijing, China); Qulian Guo
(Department of Anesthesiology, Xiangya Hospital, Central South
University, Changsha, China); Changhong Miao (Department of
Anesthesiology, Zhongshan Hospital, Fudan University, Beijing, China);
Su Min (Department of Anesthesiology, The First Affiliated Hospital of
Chongqing Medical University, China)
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