Chinese expert consensus on tetanus prophylaxis in major trauma (2026 Edition)

Abstract

Tetanus is an acute infectious disease caused by Clostridium tetani, which enters the body through contaminated wounds, proliferates under anaerobic conditions, and produces neurotoxin. Patients with major trauma are at a markedly increased risk of tetanus owing to extensive tissue injury, heavy wound contamination, and trauma-associated impairment of immune function. Existing guidelines and consensus statements on tetanus prophylaxis largely address general open wounds and provide little specific guidance for patients with major trauma, particularly those undergoing emergency life-saving surgery through expedited care pathways or admitted to the intensive care unit. To standardize tetanus prophylaxis in the management of major trauma, the writing committee convened Chinese experts in emergency medicine, trauma surgery, critical care medicine, and immunology to develop this expert consensus based on the best available evidence and current clinical practice in China. The consensus covers the fundamental principles of tetanus prophylaxis in major trauma, damage-control debridement, assessment of immune status, active and passive immunization strategies, management of special injury types, prophylaxis in immunocompromised patients, response to mass-casualty incidents, and preventive strategies under resource-limited conditions, and it aims to provide practical guidance for tetanus prophylaxis during the clinical management of major trauma.

1. Introduction

Tetanus is an acute, specific infectious disease caused by Clostridium tetani (C. tetani), which invades the body through breaches in the skin or mucosa, proliferates under anaerobic conditions, and produces tetanus neurotoxin (TeNT), leading to generalized tonic contraction and paroxysmal spasm of skeletal muscle.¹ TeNT is an extremely potent neurotoxin; its reported median lethal dose by intraperitoneal injection in mice is 0.015 ng, and the lethal dose for humans may be below 1 μg.² In the absence of medical intervention, severe tetanus carries a very high case-fatality rate. A 2025 systematic review and meta-analysis reported a overall case-fatality rate of 32.0% among hospitalized adults with tetanus.³ Vaccination is the key measure for reducing the incidence of and mortality from tetanus.⁴ The Global Burden of Disease Study 2019 showed that, although the global incidence and mortality of tetanus declined overall between 1990 and 2019, the disease burden remained concentrated in regions with a low socio-demographic index.⁵

Since China incorporated the combined diphtheria–tetanus–pertussis vaccine into its national immunization program in 1978, the incidence of neonatal tetanus has fallen substantially; however, tetanus in adults remains a concern that should not be overlooked. A 2024 meta-analysis by Chen et al.⁶ of tetanus immunoglobulin G antibody levels in healthy Chinese populations showed that the protective antibody level against tetanus declines with age in Chinese adults, indicating a substantial gap in adult booster coverage. In a 2023 analysis of 6084 cases of non-neonatal tetanus in China, Gou et al.⁷ found that the great majority of patients had no clear vaccination history or had incomplete vaccination records, and that contaminated open wounds were the predominant wound type.

The high risk of tetanus in patients with major trauma arises mainly from the following factors: (1) severe and complex wound contamination, commonly seen in open fractures, penetrating injuries, and colorectal rupture, with wounds frequently contaminated by soil and foreign material that readily introduce C. tetani spores; (2) extensive tissue necrosis and ischemia, which disrupt the local blood supply and create an anaerobic microenvironment that provides the conditions necessary for C. tetani to germinate, proliferate, and release TeNT;^8,9 and (3) pathological states such as traumatic shock, massive transfusion, hypothermia, and acidosis, which markedly suppress the host immune response and reduce clearance of C. tetani. Such patients often have not complete the full tetanus vaccination, which further increases the risk of disease.^10,11 The combination of these factors makes patients with major trauma a high-risk population that warrants particular attention in clinical tetanus prophylaxis. The target population for tetanus prophylaxis addressed in this consensus is non-neonates (>28 days of age).

During the early management of major trauma, clinical attention is usually focused on the emergency treatment of life-threatening injuries, such as airway management, hemostasis, shock resuscitation, and damage-control surgery,¹² and specific tetanus prophylaxis is often delayed or even omitted. In clinical practice, tetanus prophylaxis in patients with major trauma frequently faces multiple challenges: patients are often unable to provide a complete tetanus vaccination history because they are comatose, intubated, or sedated, making history-taking difficult; wounds are complex and heavily contaminated, further complicating preventive decision-making; and time-window conflicts among emergency surgery, resuscitation, and vaccination readily lead to delays in prophylaxis. Although several guidelines and consensus statements on tetanus prophylaxis have been published in China and worldwide,^1,13, 14, 15, 16, 17 they mainly target patients with general open wounds and lack specific guidance for patients with major trauma who have a high injury severity score (ISS), hemodynamic instability, multiple organ dysfunction, or an immunocompromised state, and thus cannot fully meet the need for precise clinical prevention.

To fill this clinical gap, this consensus was organized by the Chinese Socitety of Traumatology of the Chinese Medical Association, the Animal Injury Treatment Branch of the China Association for Disaster and Emergency Rescue Medicine, the Youth Group of the Disaster Medicine Society of the Chinese Medical Association, the Specialist Alliance for War Trauma Care of Army Hospital (Emergency Medicine), the Western China Trauma Alliance, the China County-level Hospital Emergency Alliance, and the Chongqing Emergency Care Consortium, and an expert committee comprising experts in emergency medicine, trauma surgery, critical care medicine, and immunology was established. Based on a systematic search and rigorous appraisal of the currently available global evidence, and with full consideration of clinical practice and the accessibility of medical resources in China, this expert consensus was finalized after multiple rounds of expert discussion, deliberation, and voting. It should be noted that, because high-quality randomized controlled trials (RCTs) of tetanus prophylaxis in patients with major trauma are scarce, most recommendations in this consensus are based on available observational studies, previous authoritative guidelines, and the extensive clinical experience of the experts; they are intended to provide practical, actionable guidance for clinical care and do not constitute a legal standard. This consensus has been registered on the Practice Guideline REgistration for transPAREncy (PREPARE) platform (registration number PREPARE-2026CN991).

2. Terminology

2.1. Major trauma

Trauma accompanied by severe physiological derangement that may lead to death or serious disability and that requires emergency surgery, transfusion, or other life-saving measures within the golden hour of resuscitation.¹⁸ It is generally defined by an ISS ≥ 16 and often involves injury to more than 2 anatomical regions (multiple trauma), commonly accompanied by hemodynamic instability or a need for emergency surgical intervention together with systemic treatment.¹⁹

2.2. Damage-control wound debridement

A staged surgical debridement strategy for patients with severe open trauma and extremely depleted physiological reserve. Its core concept derives from the principles of damage-control surgery. Key operative points include: at the initial operation, taking control of bleeding and contamination is the only objective—rapidly removing obvious foreign material and necrotic tissue from the wound, irrigating the wound thoroughly, placing drains, and applying temporary coverage or negative-pressure wound therapy. After the patient has been resuscitated in the ICU, the lethal triad has been corrected, and physiological stability has been restored (usually 24 – 72 h later), a second-look operation is performed, and thorough debridement and definitive repair are carried out in a stepwise, orderly manner.²⁰

2.3. Active immunization against tetanus

A preventive measure in which a tetanus toxoid-containing vaccine (TTCV) is administered so that the host immune system actively produces specific antibodies against TeNT, thereby acquiring durable immunity.²¹ TTCVs include the monovalent tetanus toxoid vaccine and tetanus-containing combination vaccines (e.g., adsorbed diphtheria–tetanus combined vaccine and adsorbed acellular diphtheria–tetanus–pertussis combined vaccine). Active immunization is characterized by a relatively slow onset (protective antibody levels are usually achieved in 2 – 4 weeks) but durable protection (immunity can last 5 – 10 years or longer after a complete vaccination series).^22,23

2.4. Passive immunization against tetanus

An intervention in which exogenous TeNT antibody preparations are injected into the body to rapidly confer temporary immune protection, used mainly for emergency prophylaxis after tetanus exposure or for the treatment of patients who have already developed the disease.^15,16 The passive immunization preparations currently in common clinical use include recombinant anti-tetanus toxin monoclonal antibody (TeNT-mAb), such as siltartoxatug; human tetanus immunoglobulin (HTIG); equine tetanus immunoglobulin F(ab')₂ fragment (here after F(ab'))₂, and equine tetanus antitoxin (TAT). A comparison of the characteristics of these preparations is shown in Table 1.

Table 1.

Comparison of the characteristics of passive immunization preparations against tetanus.^a

Preparation	Onset (h)	Duration of protection (days)	Skin test required	Usual dose	Source
TeNT-mAb	≤12	>90	No	Per label	Recombinant expression in engineered cells
HTIG	24 – 48	About 28	No	250 – 500 IU	Human plasma
F(ab')2	24 – 48	About 10	Yes	1500 – 3000 IU	Enzyme-digested equine plasma
TAT	24 – 48	About 10	Yes	1500 – 3000 IU	Equine plasma

IU: international unit; TeNT-mAb: recombinant anti-tetanus toxin monoclonal antibody; HTIG: human tetanus immunoglobulin; F(ab')₂: equine tetanus immunoglobulin F(ab')₂ fragment; TAT: equine tetanus antitoxin.

^aIn this consensus, all recommendations regarding TeNT-mAb apply to adults only. For patients younger than 18 years, passive immunization preparations should be selected according to the approved age indications and the product labeling. All passive immunization preparations should be administered in a setting where monitoring is available and where emergency treatment for anaphylaxis can be provided immediately. Product-specific contraindications, skin-test requirements, and post-administration monitoring should follow the current product labeling.

2.5. Tetanus-prone wounds

Wound types associated with a high risk of tetanus infection,^13,15,21 including but not limited to: wounds not appropriately managed more than 6 h after injury; puncture or penetrating wounds deeper than 1 cm; wounds contaminated by soil, feces, saliva, or environmental foreign material; wounds containing necrotic or ischemic tissue; firearm injuries (including shrapnel and gunshot wounds); burns and scalds; frosbite; crush injuries; and wounds with signs of established infection, etc.

3. Methods and process of consensus development

3.1. Consensus initiation and composition of the working group

Work on this consensus began in May 2025. After discussion among core experts, it was initiated and organized by the writing committee. The expert committee comprised experts from across China in emergency medicine, trauma surgery, critical care medicine, immunology, and related fields.

3.2. Refinement of clinical questions and literature search

Taking into account the management pathway of major trauma, existing guidelines and consensus statements, and the main points of controversy in clinical practice, the writing committee summarized, consolidated, and ranked candidate clinical questions and, on this basis, established a framework of recommendations. A systematic search was conducted of PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, the Wanfang Database, and the Chinese Biomedical Literature Database for relevant literature published up to 14 May 2026. Search terms included “tetanus prophylaxis”, “major trauma”, “damage control surgery”, “immunocompromised”, “mass casualty”, “tetanus immunoglobulin”, and “tetanus toxoid”, together with their Chinese equivalents.

3.3. Evidence quality appraisal and formulation of recommendations

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to appraise the quality of evidence,²⁴ which was classified as high, moderate, low, or very low. RCTs were initially rated as high-quality and observational studies as low-quality evidence; ratings were downgraded based on risk of bias, inconsistency, indirectness, imprecision, and publication bias, and were upgraded where appropriate in the presence of a large effect, a dose–response relationship, or plausible confounding that would reduce the observed effect. The strength of each recommendation was determined according to the GRADE Evidence-to-Decision framework, taking into account the quality of evidence, the anticipated benefits and risks, patients' values and preferences, resource accessibility, implementation feasibility, and the results of expert voting. For situations in which the quality of direct evidence was low, but the anticipated benefit was clear, the risk of the intervention was small, clinical feasibility was high, and delayed management could have serious consequences, a strong recommendation could be formed after thorough expert discussion.

3.4. Expert voting and consensus results

The writing committee produced a draft after multiple rounds of discussion and, on 14 May 2026, convened all experts for online discussion and voting. The experts' level of agreement with each recommendation was rated on 5 options: (a) fully agree, indispensable; (b) partly agree, with some reservation; (c) partly agree, with considerable reservation; (d) disagree, with some reservation; and (e) completely disagree. Grading criteria were established by combining the GRADE quality of evidence with the voting results: a recommendation with ≥80% of votes for option (a) was rated a “strong recommendation”; ≥80% for options (a) plus (b) was rated a “recommendation”; and ≥80% for options (a), (b), plus (c) was rated a “suggestion”. Recommendations that did not reach the threshold for a “suggestion” were deleted. The degree of consensus is expressed as the proportion of votes for option (a). A total of 12 recommendations were formed, comprising 4 strong recommendations and 8 recommendations.

4. Clinical questions and recommendations

4.1. Assessment of tetanus immune status in patients with major trauma

Recommendation 1: When the tetanus immunization history cannot be rapidly confirmed, the patient may provisionally be managed as having incomplete immunization, and a dual prophylactic strategy comprising a complete course of active immunization plus an adequate dose of passive immunization should be implemented, provided that this does not interfere with emergency resuscitation, to avoid delaying prophylaxis while awaiting confirmation of the history (strength of recommendation: strong; consensus 85.0%).

Quality of evidence and basis for recommendation 1. The GRADE quality of evidence is low. The evidence derives mainly from seroepidemiological studies, studies of rapid tetanus antibody testing, studies of immune durability, and studies of tetanus pathogenesis and post-traumatic immune changes.^6,8, 9, 10, 11^,22,23,25, 26, 27, 28, 29 Because direct RCTs of the effect of different immunization strategies on tetanus incidence in patients with major trauma are lacking, the evidence was rated as low-quality. Given that the consequences of developing tetanus after high-risk exposure in major trauma are serious, and that the potential benefit of dual prophylaxis is clear and clinically feasible, a strong recommendation was formed.

In the early management of patients with major trauma, saving life is the primary goal. However, once C. tetani spores enter a wound, they can germinate relatively quickly and begin producing toxin in the anaerobic environment created by tissue necrosis and ischemia; ^8,9 prophylaxis should therefore proceed in parallel with resuscitation and be completed as early as possible. Assessment of a trauma patient's tetanus immune status involves the following 3 aspects: (1) Assessment of the vaccination history. The protection conferred by a complete TTCV series (≥3 doses) can last 5 – 10 years; ^22,23 patients who have completed a full series and have normal immune function generally do not require a further booster within 5 years of the last TTCV dose. In clinical practice, the usual approach is to ask about the history or check vaccination records and together with the timing of the last dose, decide whether a booster is needed. However, the rate of decline of antibody levels after a complete TTCV series varies between individuals,⁶ so decisions based solely on the timing of the last dose are not entirely precise; reliance on a patient's recollection of the immunization history is also often unreliable²⁵; and in mass-casualty incidents (MCIs), the immunization history is usually unknown. Rapid tetanus antibody testing (e.g., colloidal-gold immunochromatography) can qualitatively determine within minutes whether the serum antibody level reaches a clinically useful protective level (≥0.1 IU/mL), with reported sensitivity and specificity of 85% – 95%.25, 26 Where feasible, trauma centers may draw a blood sample for rapid testing during initial resuscitation to help guide the immunization strategy. If the test result is negative or testing cannot be performed, the patient should be managed as if they had not been immunized. Although enzyme-linked immunosorbent assay provides a more precise antibody titer, it takes several hours to yield a result and is not suitable for point-of-care decision-making in the emergency setting. (2) The effect of underlying disease on immune function. In patients with underlying conditions such as human immunodeficiency virus (HIV) infection, malignancy treated with chemotherapy, use of immunosuppressants after organ transplantation, long-term glucocorticoid use, or chronic renal insufficiency, antibody levels may decline more rapidly because of impaired immune function, even in the presence of a complete previous TTCV history^27,28 (see Section 4.7 for details). (3) The effect of trauma itself on immune function. Major trauma can lead to systemic immunosuppression. The post-traumatic stress response, the interplay between excessive activation of innate immunity and suppression of adaptive immunity, the immunomodulatory effects of massive transfusion, and the inhibitory effects of hypothermia and acidosis on immune cells can all transiently reduce the capacity to respond to vaccination.^10,11 Impairment of immune function is particularly pronounced in patients with extensive burns and can persist for several weeks.²⁹

4.2. Active immunization strategy for tetanus in major trauma

Recommendation 2: All patients with open wounds from major trauma should be assessed for the need for TTCV. For those who have not completed a full series (<3 doses) or whose vaccination history is uncertain, a complete TTCV series should be started as early as possible. For patients with tetanus-prone wounds who have previously completed a full series but whose last booster was more than 5 years ago, 1 booster dose of TTCV should be administered. If more than 10 years have elapsed since the last TTCV dose, 1 booster dose should be administered regardless of wound type. Intramuscular injection into the deltoid on the lateral aspect of the upper arm of an uninjured limb is preferred (strength of recommendation: strong; consensus 85.8%).

Recommendation 3: The first post-injury dose of TTCV should be administered as soon as possible by qualified medical staff after the initial assessment has been completed, provided that this does not interfere with resuscitation. The relevant records should be completed, and vaccination should not be deferred until after discharge (strength of recommendation: recommendation; consensus 74.2%).

Quality of evidence and basis for recommendation 2 & 3. The GRADE quality of evidence is moderate for Recommendation 2 and low for Recommendation 3. Evidence that TTCV confers durable immunity, and that simultaneous injection of TTCV and HTIG at different sites does not significantly affect the immune response, derives mainly from clinical follow-up and immunogenicity studies,^22,23,30 with relatively consistent results, although there is some indirectness because the study populations were not exclusively composed of patients with major trauma; Recommendation 2 was therefore rated as moderate-quality evidence. The timing of the first post-injury dose is inferred mainly from the kinetics of the immune response, post-traumatic changes in immune function, and workflow feasibility,^{10,11,22,23,30} and studies directly comparing the clinical outcomes of different injection timings are lacking; Recommendation 3 was therefore rated as low-quality evidence. Given the good safety profile of TTCV and the risk that deferring vaccination until after discharge may result in omission, a strong recommendation and a recommendation were formed, respectively.

The classic study by Scheibel et al.²² showed that, after 3 doses of TTCV, antibody levels remained above the protective threshold for up to 13 years in 96% of participants. The follow-up study by Simonsen et al.²³ showed that antibody protection persisted for 25 years in 72% of participants. Conservatively, protection after a complete TTCV series can be estimated to last 5 – 10 years.

The preferred injection site is the deltoid of an uninjured upper arm. Patients who are hemodynamically unstable and undergoing active resuscitation may be vaccinated after stabilization; for patients undergoing emergency surgery, vaccination may be completed intraoperatively by a qualified circulating nurse; and for patients admitted to the ICU postoperatively, vaccination should be completed within 24 h of injury whenever possible.

Although there is a transient decline in immune function after major trauma, the available literature supports that most trauma patients can still mount an effective humoral immune response to toxoid.^10,11 Vaccination should not be withheld or delayed solely out of concern about post-traumatic immunosuppression. For critically ill patients with major trauma, if there is concern about a window of susceptibility before TTCV takes effect, a comprehensive judgment should be made based on wound risk, immunization history, and immune status, and a passive immunization preparation should be combined in a timely manner to provide temporary antitoxin protection.

When passive immunization preparations are used concurrently, TTCV and the passive immunization preparation should be injected at different sites, so as to avoid local neutralization of the toxoid antigen by exogenous antibody, which would affect the immune response. The study by Shin et al.³⁰ confirmed that simultaneous injection of TTCV and HTIG at different sites does not significantly affect the immune response to TTCV.

4.3. Passive immunization strategy for tetanus in major trauma

Recommendation 4: The selection of passive immunization preparations for patients with major trauma should follow the principles of safety, efficacy, and accessibility, and should be based on a comprehensive assessment of the time since the last vaccination, the wound risk level, and the host immune status (Table 2). The order of preference for passive immunization preparations is TeNT-mAb > HTIG > F(ab')₂ > TAT (strength of recommendation: strong; consensus 81.7%).

Table 2.

Quick-reference table of immunization strategies for tetanus prophylaxis in major trauma.

Immunization history/immune status	Time since last dose	Wound type	TTCV	Passive immunization preparation
Complete series (≥3 doses)	<5 years	Any type	Not required	Not required
	≥5 and <10 years	Low-risk	Not required	Not required
	≥5 and <10 years	High-riska	One booster dose	May be consideredb
	≥10 years	Any type	One booster dose	Recommended
Incomplete series (<3 doses) or uncertain	-	Any type	Complete series	Recommended
Mild immune impairment	<5 years	Any type	Not required	May be consideredb
	≥5 years	Any type	One booster dose	Recommended
Severe immune impairment	-	Any type	Vaccinatec	Recommended
<12 months after HSCT	-	Any type	Not recommended	Recommended
≥12 months after HSCT	-	Any type	Complete series	Recommended

TTCV: tetanus toxoid-containing vaccine; HSCT: hematopoietic stem cell transplantation.

^aFor the definition of high-risk wounds, see Section 2.5.

^bEspecially applicable to patients with heavily contaminated wounds, a delay of >6 h before presentation, or extensive necrotic tissue.

^cThe effect of active immunization may be unreliable, and testing of antibody levels for assessment is recommended where feasible. Before administering TTCV, contraindications and any history of severe allergic reactions should be assessed, and post-vaccination observation should follow national regulations.

Quality of evidence and basis for recommendation 4. The GRADE quality of evidence is moderate. The main evidence comparing TeNT-mAb with HTIG derives from a randomized, double-blind, active-controlled phase 3 trial;³¹ the evidence for HTIG, F(ab')₂, and TAT derives mainly from pharmacokinetic studies, case data, guidelines, and expert consensus statements.^7,16,32, 33, 34, 35 Because the main outcomes were mostly neutralizing antibody levels, onset time, and duration of protection, and direct clinical-outcome evidence on tetanus incidence in patients with major trauma is limited, the evidence was rated as moderate-quality. Given that passive immunization can rapidly confer protection and that the preparations differ clearly in safety, speed of onset, and accessibility, a strong recommendation was formed.

The value of passive immunization lies in directly injecting exogenous antibody to provide temporary protection during the window before active immunization takes effect. This is particularly necessary for patients with major trauma whose immunization history is uncertain or who have not been immunized.

4.3.1. Recombinant TeNT-mAb

A randomized, double-blind, active-controlled phase 3 trial (n = 675) published by Liang et al.³¹ in Nature Medicine in 2025 showed that, 12 h after injection of 10 mg, TeNT-mAb enabled 95.4% of participants to reach the minimum protective level (anti-tetanus neutralizing antibody titer ≥ 0.01 IU/mL), compared with only 53.2% in the HTIG 250 IU group (p < 0.0001). The duration of protection with TeNT-mAb can exceed 90 days, significantly longer than with HTIG (about 28 days) and TAT/F(ab')₂ (about 10 days). TeNT-mAb is a recombinant product with no risk of bloodborne infection, requires no skin test, and has an extremely low incidence of allergic reactions, which can simplify the clinical workflow.

4.3.2. HTIG

Derived from human plasma, HTIG contains no heterologous protein, causes few adverse reactions, and requires no skin test. The usual dose is 250 IU, which may be increased to 500 IU in patients with heavy contamination or a delay of more than 24 h before presentation.³³ The duration of protection is approximately 28 days.^16,31 Notably, a small pharmacokinetic study (n = 12) by Wahlberg et al.³⁴ found that, 48 h after injection of 500 IU of HTIG, serum antibody titers remained low in some participants, indicating individual variation in the immediate protective effect of HTIG; this may be one reason why a small number of patients still develop the disease after receiving HTIG. As a blood product, HTIG is subject to constraints on blood supply.

4.3.3. F(ab')₂ and TAT

Both F(ab')₂ and TAT are equine passive immunization preparations against tetanus. F(ab')₂, after enzymatic digestion and purification, has most of the crystallizable fragment region removed and has a lower incidence of allergic reactions than traditional TAT; TAT, an equine tetanus antitoxin, is a heterologous protein preparation with a relatively high risk of allergic reactions. An intradermal test must be performed before use of either. The duration of protection of both is approximately 10 days,¹⁶ and it may be shortened after repeated injections. The dose is 1500 – 3000 IU per administration, and in patients with heavy contamination, a repeat injection after 1 week may be considered to prolong protection.³⁵ If the skin test is positive, another passive immunization preparation should preferably be substituted; if no alternative is available and use is genuinely necessary, desensitizing injection may be carried out according to protocol.

The order of preference for passive immunization preparations is TeNT-mAb > HTIG > F(ab')₂ > TAT. In primary-care facilities, F(ab')₂/TAT may be the only accessible preparation and should be used under strict skin-testing conditions.

The pooled analysis by Gou et al.⁷ found that, among 6084 cases of tetanus in China, 2.17% had received a passive immunization preparation before onset. Cases have also been reported in patients with a complete previous TTCV history.¹⁶ Therefore, for patients with high-risk exposure whose last TTCV dose was more than 10 years ago, combining a passive immunization preparation—especially TeNT-mAb—with a TTCV booster is a strategy worth considering.

4.4. Tetanus prophylaxis during early in-hospital management of major trauma

Recommendation 5: Tetanus prophylaxis should be incorporated into the standardized management of major trauma as a routine component of the secondary survey, with particular attention to full-body exposure to avoid missing wounds. It is recommended that, once the trauma team has completed initial resuscitation and the patient's hemodynamics have stabilized, tetanus risk assessment and immunoprophylaxis be initiated immediately. For patients requiring emergency surgery, tetanus risk assessment and immunoprophylaxis should be incorporated into the perioperative management workflow and advanced in parallel, provided that this does not interfere with the initiation and conduct of the emergency operation (strength of recommendation: strong; consensus 80.8%).

Quality of evidence and basis for recommendation 5. The GRADE quality of evidence is low. The evidence derives mainly from tetanus diagnosis and treatment standards, studies of pathogenic mechanisms, studies of trauma-related immune function, and studies of admission pathways for non-neonatal tetanus.^1,8, 9, 10, 11^,36 Because direct comparative studies of improved clinical outcomes after incorporating tetanus prophylaxis into the standardized management of major trauma are lacking, the evidence was rated as low-quality. Given that this measure is compatible with the trauma secondary-survey workflow, carries a low implementation risk, and helps reduce omission of prophylaxis, a strong recommendation was formed.

Early in-hospital management of major trauma follows the principles of Advanced Trauma Life Support, proceeding according to the primary survey and resuscitation workflow. Resuscitation to save life has the highest priority. However, once C. tetani spores enter a wound, they can germinate within hours and begin producing toxin in the hypoxic, necrotic-tissue-rich microenvironment.^8,9 The incubation period of tetanus is usually 3 – 21 days, with a mean of approximately 8 days; in a few cases, it may be as short as 1 day, and a shorter incubation period usually indicates more severe disease and is associated with a poor prognosis.¹ Injection of passive immunization preparations should therefore be completed as early as possible.

Specific implementation recommendations are as follows: During the primary survey and resuscitation phase (approximately 0 – 1 h), efforts should concentrate on life-saving resuscitation. During this phase, triage staff may record the patient's identity information to facilitate subsequent retrieval of vaccination records. If blood is drawn for cross-matching or laboratory tests, an additional tube of blood may, where feasible, be collected at the same time for rapid tetanus antibody testing. During the secondary survey (after resuscitation), all wounds should be examined individually, and tetanus risk and immune status should be assessed simultaneously; immunoprophylaxis should be initiated according to the assessment. For patients requiring passive immunization, given that patients with major trauma require prompt prophylaxis and the clinical time window is limited, immediate injection of TeNT-mAb is recommended; if TeNT-mAb is not available, HTIG may be chosen. For patients requiring active immunization, the first dose of TTCV should be administered into the deltoid of the contralateral upper arm. For patients requiring emergency surgery, if vaccination cannot be completed before surgery, it may be completed intraoperatively by a qualified circulating nurse or completed postoperatively, and the execution should be clearly recorded in the anesthesia and nursing records. The presence of spasms on admission, a heart rate ≥ 110 beats/min, and an interval of ≥ 3 days from onset to presentation can serve as high-risk features for the early identification of the risk of progression to severe tetanus. Patients with these features are recommended to be admitted directly to the ICU for monitoring and treatment, so as to reduce treatment delay and improve prognosis.³⁶

4.5. Debridement of heavily contaminated wounds and tetanus prophylaxis in major trauma

Recommendation 6: For heavily contaminated open wounds in patients with major trauma, debridement should follow these principles: (1) initial debridement should remove all visible foreign material and obvious necrotic tissue, with copious irrigation using normal saline, focusing on controlling bleeding and contamination rather than pursuing complete one-stage debridement; (2) the wound should be left open or managed with negative-pressure wound therapy, and one-stage closure of a heavily contaminated wound is generally not recommended; if closure is required, the conditions of adequate debridement, effective control of contamination, and an acceptable risk of infection should be met; (3) at second debridement (usually after 48 – 72 h), the wound should be comprehensively reassessed and residual necrotic tissue thoroughly removed, and if immunoprophylaxis was not completed during the first operation it should be administered immediately; and (4) at each debridement, the wound condition, the debridement process, and the execution of tetanus prophylaxis should be recorded (strength of recommendation: recommendation; consensus 76.7%).

Quality of evidence and basis for recommendation 6. The GRADE quality of evidence is very low. The evidence derives mainly from the concept of damage-control debridement, recommendations for initial wound management in austere environments, and expert experience,^20,37, 38, 39 and comparative studies directly evaluating the effect of different debridement strategies on tetanus incidence in patients with major trauma are lacking; the evidence was therefore rated as very low-quality. Given that removing foreign material and necrotic tissue and keeping the wound open for drainage can reduce the anaerobic environment required for C. tetani growth, and that this is consistent with the surgical principles for managing heavily contaminated wounds, a recommendation was formed.

Damage-control debridement is an important staged management strategy for patients with major trauma who have heavily contaminated open wounds, particularly those with depleted physiological reserve, hemodynamic instability, or an inability to tolerate complete one-stage debridement.²⁰ Initial debridement should take control of bleeding and contamination as the primary objectives, removing as much visible soil, gravel, clothing fragments, shrapnel, and other foreign material and clearly necrotic tissue as possible, irrigating the wound thoroughly, and keeping it open for drainage or applying temporary coverage; tissue of uncertain viability may be left for reassessment at second debridement. Second-look exploration and debridement are usually performed after the patient has been resuscitated and, when the condition permits, focusing on removing residual necrotic tissue and assessing control of wound contamination. At each debridement, whether TTCV and the passive immunization preparation have been administered according to indication, at an adequate dose, and at different sites should be checked at the same time, and clearly documented in the operative, anesthesia, or nursing records; if not completed during the first operation, they should be administered as early as possible. It is important to emphasize that although debridement reduces the spore burden within the wound and disrupts the anaerobic microenvironment, it cannot neutralize TeNT that has already been produced or has bound to neural tissue. Debridement therefore cannot substitute for active immunization with TTCV or for passive immunoprophylaxis; the two interventions should instead be undertaken concurrently, guided by risk assessment.37, 38, 39

4.6. Tetanus prophylaxis for special injury types

Recommendation 7: The following special injury types warrant particular attention to tetanus prophylaxis and should be managed according to high-risk exposure standards, with the corresponding preventive measures implemented for each: (1) confirmed or strongly suspected open skull base fracture; (2) colorectal rupture caused by blunt injury; (3) penetrating thoracic or abdominal injury with visceral injury; (4) severe closed soft-tissue injury requiring fasciotomy for decompression; (5) open bone or joint injury; and (6) burns and frostbite (strength of recommendation: recommendation; consensus 67.5%).

Quality of evidence and basis for recommendation 7. The GRADE quality of evidence is low. The evidence derives mainly from tetanus diagnosis and treatment standards, studies of pathogenic mechanisms, and studies of post-burn changes in immune function.^1,8,29 High-quality direct comparative evidence on the association between different special injury types and the risk of tetanus is lacking, and some judgments are based on mechanistic inferences regarding the source of contamination, tissue ischemia and necrosis, and the formation of an anaerobic environment the evidence was therefore rated as low-quality. Given that these injuries are often accompanied by contamination, necrotic tissue, or impaired immune function, and that managing them as high-risk exposures has good clinical rationale, a recommendation was formed.

Different types of severe injury carry different risks of tetanus and should be considered by category. An open skull base fracture accompanied by cerebrospinal fluid leakage creates communication between the intracranial space and the nasopharynx, increasing the risk of invasion by exogenous pathogens; it should therefore be managed as a high-risk exposure. C. tetani is one of the intestinal colonizing bacteria. When colorectal injury causes leakage of intestinal contents, C. tetani spores can directly contaminate the abdominal cavity and surrounding tissues, constituting a risk of endogenous infection.⁸ Therefore, gastrointestinal perforation or rupture—particularly colorectal injury—warrants tetanus prophylaxis even in the absence of an external open wound. All burns (including thermal, chemical, and electrical burns) are regarded as contaminated wounds, because the burn wound contains necrotic tissue that readily creates an anaerobic environment favorable to C. tetani proliferation. In addition, the severe impairment of immune function caused by burns (decreased immunoglobulins, suppression of cellular immunity, etc.) can persist for several weeks,²⁹ further increasing the risk. It is recommended that patients with burns routinely receive a passive immunization preparation and that TTCV be started as early as possible after stabilization. Severe frostbite can cause tissue necrosis and microcirculatory impairment, creating an anaerobic environment; it should be managed as a contaminated wound and tetanus prophylaxis should be provided. Closed crush injury and compartment syndrome are initially closed injuries, but an extensive open wound is created after fasciotomy for decompression. After decompression, the muscle tissue is frequently accompanied by ischemia–reperfusion injury and necrosis of varying degrees, and it should be managed as an open high-risk injury from the time of decompression.¹ Open fractures (especially Gustilo type III) have heavy wound contamination and extensive soft-tissue injury and should be given the highest-risk prophylaxis; pelvic fracture combined with injury to the digestive or genitourinary system is also a high-risk type. Penetrating thoracic and abdominal injuries (firearm and stab wounds) have severe necrosis of the deep tissue along the ballistic or wound tract, often with retained foreign material, and should routinely receive prophylaxis. In patients with multiple trauma, all wounds should be examined one by one during the secondary survey, and other sites should not be missed because of surgery on one site.

4.7. Tetanus prophylaxis for immunocompromised patients with major trauma

Recommendation 8: Immunocompromised trauma patients can safely receive TTCV and passive immunization preparations. Management stratified by the degree of immune impairment is recommended: (1) for patients with mild impairment, general-population prophylaxis principles should be followed, with the TTCV booster interval shortened to 5 years, and even if the last dose was administered less than 5 years previously, passive immunization may be considered according to the degree of wound contamination and the patient's immune status; (2) for patients with severe impairment, tetanus antibody levels should be tested to guide decision-making where feasible, and a passive immunization preparation should be given routinely when testing is not feasible; and (3) for hematopoietic stem cell transplantation (HSCT) patients, a passive immunization preparation should be administered if trauma occurs within 12 months after transplantation (TTCV is not recommended during this period), and a complete TTCV series should be restarted 12 months or more after transplantation (strength of recommendation: recommendation; consensus 74.2%).

Quality of evidence and basis for recommendation 8. The GRADE quality of evidence is low. The evidence includes the TeNT-mAb clinical trial³¹ and studies of vaccine responses in patients with solid organ transplantation, HIV infection, chronic renal insufficiency, chronic liver disease, diabetes, chemotherapy for hematological malignancy, and HSCT,^27,28,40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52 as well as guidelines or expert recommendations on vaccination in immunocompromised individuals.53, 54, 55, 56 Because of the great heterogeneity of the populations, the fact that study outcomes were mostly antibody levels or immune responses rather than post-traumatic tetanus incidence in major trauma, and the derivation of some evidence from guidelines and expert opinion, the evidence was rated as low-quality. Given that TTCV is an inactivated toxoid vaccine, that passive immunization preparations do not depend on the patient's own immune response, and that immunocompromised patients are at higher risk once exposed, a recommendation was formed.

Immunocompromised patients with major trauma face a double blow of underlying immune deficiency and trauma-related immunosuppression.

Patients with mild immune impairment include: those receiving conventional anti-rejection medication after solid organ transplantation;²⁷ those taking glucocorticoids (equivalent to prednisone < 20 mg/day) together with conventional immunosuppressants (e.g., methotrexate, azathioprine);^40,41 patients on dialysis for chronic renal insufficiency;^42,43 and HIV-infected individuals with a CD4⁺ T-lymphocyte count ≥ 300/μL.²⁸ In addition, patients with severe chronic liver disease (e.g., liver fibrosis, advanced hepatitis) have impaired vaccine responses due to T/B-cell dysfunction,44, 45, 46, 47 and patients with type 2 diabetes exhibit weakened immune memory and rapid antibody decline.⁴⁸ Such patients can produce protective antibodies after TTCV, but the antibodies decline faster than in the general population; it is therefore recommended that TTCV and passive immunization preparations after trauma follow the principles for the general population and that, on this basis, the booster interval be shortened to within 5 years.

Patients with severe immune impairment include: those using anti-cluster of differentiation 20 (CD20) monoclonal antibodies (e.g., rituximab);²⁷ those receiving chemotherapy for hematological malignancy;^49,50 and HIV-infected individuals with a CD4⁺ T-lymphocyte count < 300/μL.²⁸ These patients do not necessarily produce protective levels of antibody after TTCV. Antibody levels may be tested to guide decision-making where feasible; where testing is not feasible, all severely immunocompromised trauma patients should be given a passive immunization preparation. In this population, TeNT-mAb offers distinct advantages due to its rapid onset of action and favorable safety profile.

HSCT patients: After HSCT, previously acquired immune memory is effectively erased,^51,52 and such patients should be regarded as having no TTCV history. International guidelines recommend restarting a complete TTCV series at 12 months after transplantation,53, 54, 55 and the effect of restarting immunization after transplantation is similar to that in the general population.⁵¹ For injury within 12 months after transplantation, because immune reconstitution is not yet complete, TTCV is not recommended, and a passive immunization preparation should be injected to provide temporary protection.

TTCV is an inactivated toxoid vaccine that can be safely used in immunocompromised patients with no risk of causing disease.⁵⁶ The safety of passive immunization preparations is likewise unaffected by immune status.

4.8. Recommendation on “delayed management” of tetanus prophylaxis

Recommendation 9: When more than 24 h has elapsed after high-risk tetanus exposure without initiation of prophylaxis, a delayed-management procedure should be initiated. If a passive immunization preparation is needed, TeNT-mAb is recommended as the first choice, followed by 500 IU of HTIG (strength of recommendation: recommendation; consensus 71.7%).

Quality of evidence and basis for recommendation 9. The GRADE quality of evidence is low. The evidence derives mainly from studies comparing the antibody kinetics of TeNT-mAb and HTIG,³¹ studies of the growth and toxin-production mechanisms of C. tetani,^8,9 and a review of the recognition and management of tetanus.⁵⁷ Because direct clinical comparative studies among the delayed-management time window, the choice of passive immunization preparation, and tetanus incidence in major trauma are lacking, with indirectness and imprecision, the evidence was rated as low-quality. Given that the risk of short-incubation cases cannot be ignored in delayed management and that rapidly establishing neutralizing antibody protection has potential benefit, a recommendation was formed.

In clinical practice, tetanus prophylaxis may be delayed for patient-related or facility-related reasons. Delayed presentation by the patient or referral from a facility lacking comprehensive management capacity may both result in delayed prophylaxis.

Animal experiments have found that, after entering a wound suitable for its growth, C. tetani grows slowly within the first 6 h but enters a phase of rapid growth between 6 h and 24 h, potentially producing a dose of toxin sufficient to cause disease, and reaches peak growth at 24 – 48 h.⁸ Another study found that C. tetani grows rapidly within 10 h and produces toxin between 10 h and 40 h.⁹ Although the incubation period of tetanus is 3 – 21 days in most patients, 10% of patients have an incubation period shorter than 2 days, and the incubation period may be as short as 1 day.⁵⁷ Therefore, for situations with a risk of tetanus, especially those with obvious tissue necrosis, ischemia, or retained foreign material, tetanus prophylaxis should be initiated as early as possible. If a high-risk tetanus situation persists more than 24 h after injury without prophylaxis having been initiated, it can be regarded as delayed management. As a novel passive immunization preparation against tetanus, TeNT-mAb confers protection more rapidly after injection. Studies have found that TeNT-mAb confers protection significantly faster than HTIG 250 IU,³¹ giving it a potential advantage in preventing disease in patients with a short incubation period or delayed management. For patients with delayed management who require a passive immunization preparation, TeNT-mAb is the first choice, followed by a double dose of HTIG (500 IU). Nevertheless, delayed management should still be based on individualized assessment, and the benefit diminishes as the delay lengthens.

4.9. Management of tetanus in patients with major trauma during MCIs and under resource-limited conditions

Recommendation 10: Tetanus prophylaxis in an MCI should follow the principles of speed, efficiency, and order, with specific requirements including: (1) during triage, all casualties with open injuries should be clearly marked and simultaneously incorporated into a dedicated tetanus-prophylaxis management workflow to avoid omission; a simple traceable record system should be established, and a “T” mark placed on a waterproof wristband or triage tag to clearly indicate that the patient has received tetanus prophylaxis, ensuring that each patient's prophylaxis is traceable and verifiable; (2) for batches of casualties with open wounds, when the tetanus immune status cannot be rapidly confirmed, a passive immunization preparation should be given immediately together with one dose of TTCV; and (3) if the supply of passive immunization preparations is limited, they should be preferentially allocated to severely injured patients whose immunization history is uncertain or clearly incomplete, prioritizing the prevention needs of high-risk populations (strength of recommendation: recommendation; consensus 74.2%).

Recommendation 11: In the absence of tetanus immunization preparations or under resource-limited conditions (e.g., field environments, remote areas, cold-chain failure), tetanus prophylaxis should adopt the following targeted strategies: (1) thorough surgical debridement and open wound drainage are the most important preventive measures; (2) one-stage suture of a contaminated wound is not recommended in the field environment; (3) antibiotics are used for infection control of contaminated wounds but are not a core measure for post-exposure tetanus prophylaxis and cannot replace immunoprophylaxis; and (4) patients should be transferred as early as possible to a facility that has immunization preparations (strength of recommendation: recommendation; consensus 73.3%).

Quality of evidence and basis for recommendation 10 & 11. The GRADE quality of evidence is very low for both Recommendation 10 and Recommendation 11. The evidence derives mainly from the results on rapid establishment of antibody protection in the TeNT-mAb clinical trial,³¹ recommendations for post-exposure prophylaxis in MCIs, and guidelines for wound management in austere environments.37, 38, 39^,58 Because RCTs are difficult to conduct in MCIs and resource-limited environments, the available evidence is mostly indirect evidence, public-health emergency recommendations, and expert experience, and direct comparisons of the effect of different allocation strategies on tetanus incidence are lacking; the evidence was therefore rated as very low-quality. Given that the above measures can improve the traceability of managing batches of casualties, reduce omission of prophylaxis, and accord with the principles of resource allocation in disaster medicine, a recommendation was formed.

In MCIs caused by earthquakes, war, terrorist attacks, typhoons, and tsunamis, large numbers of casualties are produced in a short time, medical resources are strained, information recording is chaotic, and the risk of a tetanus outbreak is high. Tetanus cases were reported after both the 2008 Wenchuan earthquake and the 2010 Haiti earthquake. The Recommendations for Postexposure Interventions after Bombings and Other Mass-Casualty Events issued by the U.S. Centers for Disease Control and Prevention in 2008 explicitly identified tetanus prophylaxis as a core component of the medical response to such events.⁵⁸

The particular challenges faced in an MCI include: the large number of casualties, which makes detailed immunization-history-taking for each person impractical; possible shortages of vaccines and passive immunization preparations; and record systems that may be paralyzed or incomplete. A simplified “assume not immunized” strategy should be adopted. The principles of allocation when resources are short are as follows: TTCV can be administered universally to all casualties with open injuries (the vaccine is low-cost and has relatively simple storage requirements); passive immunization preparations should be preferentially used for severely injured patients whose immunization history is uncertain or who are clearly not immunized, and the execution of prophylaxis should be noted on the triage tag to facilitate continuity during evacuation and transfer. When formulating a tetanus prevention and control plan for MCIs, given that TeNT-mAb has the features of high accessibility, no need for a skin test, rapid injection, and establishment of protection within 12 h,³¹ it may be considered as a reserve passive immunization drug.

In field, remote, or post-disaster environments where infrastructure is disrupted, cold-chain systems may fail, and vaccines and immunoglobulins may be unavailable.³⁷ In such situations, casualties experience long delays in seeking care, and their wounds are exposed to a contaminated environment for a long time, further increasing the risk of tetanus. When no immunization preparation is available, surgical debridement is the only means that can directly reduce the bacterial load in the wound and improve the microenvironment: removing spore-bearing foreign material and necrotic tissue, irrigating thoroughly, and keeping the wound open for drainage to prevent the formation of a closed anaerobic environment. Metronidazole is effective against C. tetani and can suppress bacterial proliferation and toxin production to some extent, but it cannot neutralize toxin already bound to neural tissue and cannot replace immunoprophylaxis.^38,39 Once an immunization preparation becomes available, it should be administered without delay.

4.10. Quality control and follow-up management of tetanus prophylaxis in patients with major trauma

Recommendation 12: It is recommended that trauma centers and emergency departments at all levels, where feasible, incorporate tetanus prophylaxis into the quality-control indicator system for major trauma care and establish an in-hospital tetanus-prophylaxis reminder system and a sound post-discharge follow-up mechanism (strength of recommendation: recommendation; consensus 79.2%).

Quality of evidence and basis for recommendation 12. The GRADE quality of evidence is moderate. The evidence derives mainly from a systematic review showing that patient reminder and recall interventions improve vaccination rates,⁵⁹ as well as studies of trauma checklists, clinical decision support, and surveys of tetanus-prophylaxis practice.60, 61, 62, 63, 64, 65 Although most of the evidence concerns process indicators or general vaccination completion rates, which have some indirectness with respect to tetanus incidence in patients with major trauma, the direction of the results is relatively consistent, indicating that standardized reminders, quality control, and follow-up can reduce omission of vaccination; the evidence was therefore rated as moderate-quality. Given that this measure has a low implementation risk and controllable resource requirements and benefits closed-loop management, a recommendation was formed.

The main challenge in tetanus prophylaxis for patients with major trauma is often not a technical problem but a management one—omission. In the intense pace of resuscitation, tetanus prophylaxis is easily overlooked.60, 61, 62 The following measures are recommended to improve quality: incorporating tetanus assessment into the trauma secondary-survey checklist;⁶³ designating a specific role in the trauma team (e.g., a trauma coordinating nurse) to be responsible for assessment and execution;⁶⁴ setting up a reminder function in the hospital information system;⁶⁵ clearly noting in the discharge summary the prophylactic measures already completed and the schedule for subsequent vaccination; and establishing a follow-up reminder mechanism for patients who have received only the first dose of TTCV.^59,60 Quality-control indicators for tetanus prophylaxis may include the rate of tetanus risk assessment, the execution rate of vaccination in patients requiring TTCV, the execution rate of injection in patients requiring a passive immunization preparation, and the completion rate of the full TTCV series.⁶¹

5. Workflow for tetanus prophylaxis in major trauma

To facilitate clinical practice, this consensus has established a standardized workflow (Fig. 1).

Fig. 1.

Standardized workflow for tetanus prophylaxis in patients with major trauma. xABCDE: emergency hemorrhage control, airway, breathing, circulation, disability, and environmental/exposure control; Rec.: recommendation; HSCT: hematopoietic stem cell transplantation; TTCV: tetanus toxoid-containing vaccine; TeNT-mAb: recombinant anti-tetanus toxin monoclonal antibody; HTIG: human tetanus immunoglobulin; F(ab')₂: equine tetanus immunoglobulin F(ab')₂ fragment; TAT: equine tetanus antitoxin; NPWT: negative-pressure wound therapy.

CRediT authorship contribution statement

Yang Li: Writing – original draft. Si Liu: Writing – review & editing. Ping Jin: Writing – review & editing. Xiaoyong Mao: Visualization, Formal analysis, Data curation. Qiaoling Song: Project administration, Formal analysis, Data curation. Lei Li: Writing – review & editing, Methodology, Investigation, Conceptualization. Zilong Li: Writing – review & editing, Supervision, Conceptualization. Bin Yu: Writing – review & editing, Supervision, Conceptualization. Chuanlin Wang: Writing – review & editing, Supervision, Conceptualization. Lianyang Zhang: Writing – review & editing, Supervision, Conceptualization.

Expert workgroup members and authorship contribution statement

Review Experts (listed alphabetically by surname)

Yijun Bao, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Dingyuan Du, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.

Shouping Gong, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Wubing He, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.

Lijun Hou, The Second Affiliated Hospital of Naval Medical University, Shanghai, China.

Zhiyong Hou, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Yanjun Hu, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Fang Ji, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Xieyuan Jiang, Beijing Jishuitan Hospital, Beijing, China.

Kainan Li, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

Lianxin Li, Shandong Provincial Hospital, Jinan, China.

Guangyao Liu, China-Japan Union Hospital of Jilin University, Changchun, China.

Guohui Liu, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Peng Liu, Daping Hospital, Army Medical University, Chongqing, China.

Tao Liu, Henan Provincial People's Hospital, Zhengzhou, China.

Gang Lyu, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Xin Ma, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Xiguang Sang, Qilu Hospital of Shandong University, Jinan, China.

Hongtao Sun, Characteristic Medical Center of the Chinese People's Armed Police Force, Tianjin, China.

Peifu Tang, Chinese PLA General Hospital, Beijing, China.

Guanglin Wang, West China Hospital, Sichuan University, Chengdu, China.

Tianbing Wang, Peking University People's Hospital, Beijing, China.

Ce Yang, Daping Hospital, Army Medical University, Chongqing, China.

Xiaofeng Yang, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Qi Yao, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Dianying Zhang, Peking University People's Hospital, Beijing, China.

Kun Zhang, Xi'an Honghui Hospital, Xi'an, China.

Wei Zhang, PLA General Hospital, Beijing, China.

Longpo Zheng, Shanghai Tenth People's Hospital, Shanghai, China.

Consensus Writing Committee (listed alphabetically by surname)

Shanmu Ai, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.

Quanwei Bao, Daping Hospital, Army Medical University, Chongqing, China.

Yanfen Chai, Tianjin Medical University General Hospital, Tianjin, China.

Haiming Chen, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Longwang Chen, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Xianqiang Chen, Fujian Medical University Union Hospital, Fuzhou, China.

Yong Chen, The Affiliated Dazu's Hospital of Chongqing Medical University, Chongqing, China.

Dapeng Cheng, Yuncheng Central Hospital, Yuncheng, China.

Zhigang Cui, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin, China.

Xingbo Dang, Shaanxi Provincial People's Hospital, Xi'an, China.

Weiwei Ding, General Hospital of Eastern Theater Command, Nanjing, China.

Yujin Dong, Zhongshan Hospital Affiliated to Dalian University, Dalian, China.

Honglei Dou, Yidu Central Hospital of Weifang, Qingzhou, China.

Ke Feng, General Hospital of Ningxia Medical University, Yinchuan, China.

Yong Fu, The Second Affiliated Hospital of University of South China, Hengyang, China.

Tao Gan, Liuzhou People's Hospital, Liuzhou, China.

Ping Gong, Shenzhen People's Hospital, Shenzhen, China.

Guancheng Guo, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Wei Guo, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Zhitao Guo, Tianjin Xiqing Hospital, Tianjin, China.

Guangliang Hong, Quzhou Hospital Affiliated to Wenzhou Medical University, Quzhou, China.

Peiyang Hu, Tiantai County People's Hospital, Taizhou, China.

Qiang Hu, Panzhihua Central Hospital, Panzhihua, China.

Guangbin Huang, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.

Jian Huang, Chongqing Liangjiang New Area People's Hospital, Chongqing, China.

Mingwei Huang, Jinhua Central Hospital Medical Group, Jinhua, China.

Nan Jiang, China-Japan Union Hospital of Jilin University, Changchun, China.

Ping Jin, Yangming Hospital Affiliated to Ningbo University/Yuyao People's Hospital, Ningbo, China.

Hongxu Jin, General Hospital of Northern Theater Command, People's Liberation Army, Shenyang, China.

Liangjun Lang, Yangming Hospital Affiliated to Ningbo University/Yuyao People's Hospital, Ningbo, China.

Zhanfei Li, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Haishan Li, The Second People's Hospital of Hefei, Anhui, China.

He Li, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Hongbin Li, The Third People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

Junjie Li, The First Affiliated Hospital of Air Force Medical University, Xi'an, China.

Lei Li, Daping Hospital, Army Medical University, Chongqing, China.

Wen Li, Renmin Hospital of Wuhan University, Wuhan, China.

Xiaolong Li, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Yang Li, Daping Hospital, Army Medical University, Chongqing, China.

Yunming Li, General Hospital of Western Theater Command, Chengdu, China.

Zhangping Li, Jinhua Hospital Affiliated to Wenzhou Medical University, Jinhua, China.

Zilong Li, Yangming Hospital Affiliated to Ningbo University/Yuyao People's Hospital, Ningbo, China.

Jian Liang, The Affiliated Dazu's Hospital of Chongqing Medical University, Chongqing, China.

Zhenzong Lin, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China.

Fayou Liu, People's Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong, China.

Shaoguang Liu, Gansu Provincial People's Hospital, Lanzhou, China.

Guie Liu, Daping Hospital, Army Medical University, Chongqing, China.

Si Liu, Peking University First Hospital, Beijing, China.

Yuechen Liu Xingyi People's Hospital, Xingyi, China.

Zhifeng Liu, General Hospital of Southern Theater Command, People's Liberation Army, Guangzhou, China.

Chengjun Long, The Second Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Feng Lu, Huishan District People's Hospital of Wuxi, Wuxi, China.

Zhongqiu Lu, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Guofu Luo, Lijiang People's Hospital, Lijiang, China.

Yu Ma, Chongqing Emergency Medical Center/Central Hospital Affiliated to Chongqing University, Chongqing, China.

Qiang Ma, Qinghai University Affiliated Hospital, Xining, China.

Xiaoyong Mao, Daping Hospital, Army Medical University, Chongqing, China.

Yu Meng, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Yanhong Ouyang, Hainan General Hospital, Haikou, China.

Jing Peng, Daping Hospital, Army Medical University, Chongqing, China.

Na Peng, General Hospital of Southern Theater Command, People's Liberation Army, Guangzhou, China.

Haidong Qin, Nanjing First Hospital, Nanjing, China.

Nan Qin, Daping Hospital, Army Medical University, Chongqing, China.

Eryue Qiu, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.

Jianshe Shi, 910th Hospital of the Joint Logistic Support Force, Quanzhou, China.

Rongmao Shi, 920th Hospital of the Joint Logistic Support Force, Kunming, China.

Qichun Song, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Qiaoling Song, Daping Hospital, Army Medical University, Chongqing, China.

Chuanzheng Sun, The Third Xiangya Hospital of Central South University, Changsha, China.

Dahui Sun, The First Hospital of Jilin University, Changchun, China.

Huamin Tang, Guangxi International Zhuang Medicine Hospital, Nanning, China.

Youqing Tang, Guangdong Second Provincial General Hospital, Guangzhou, China.

Cheng Tao, The Second Xiangya Hospital of Central South University, Changsha, China.

Pan Tian, Hospital of the 82nd Group Army, Baoding, China.

Huasheng Tong, General Hospital of Southern Theater Command, People's Liberation Army, Guangzhou, China.

Dong Wan, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Chuanlin Wang, Peking University People's Hospital, Beijing, China.

Bowei Wang, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Chunqing Wang, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Hongqi Wang, Shangqiu First People's Hospital, Henan, China.

Jian Wang, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Kai Wang, General Hospital of Eastern Theater Command, Nanjing, China.

Liang Wang, Harbin Fifth Hospital, Harbin, China.

Nan Wang, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Song Wang, Tianjin First Central Hospital, Tianjin, China.

Xiaolong Wang, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Yanjun Wang, Xi'an Honghui Hospital, Xi'an, China.

Fei Xia, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Qiang Xiang, The First Affiliated Hospital of Army Medical University, Chongqing, China.

Ping Xu, Zigong Fourth People's Hospital, Zigong, China.

Shanxiang Xu, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Yongqing Xu, 920th Hospital of the Joint Logistic Support Force, Kunming, China.

Bo Yang, Suining Central Hospital, Sichuan, China.

Jun Yang, Chuzhou Hospital Affiliated to Anhui Medical University/Chuzhou First People's Hospital, Chuzhou, China.

Peng Yang, The First Affiliated Hospital of Soochow University, Suzhou, China.

Yuetao Yang, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Zhao Yang, Tianjin Hospital, Tianjin, China.

Yuanzhang Yao, Xiushan County People's Hospital, Chongqing, China.

Shupei Ye, Dongguan Songshan Lake Central Hospital, Dongguan, China.

Feng Yi, Yueyang Central Hospital, Yueyang, China.

Mengqiu Yi, Songyuan Jilin Oilfield Hospital, Songyuan, China.

Wenpeng Yin, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Bin Yu, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Anyong Yu, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Huijie Yu, The First Hospital of Jiaxxing, Jiaxing, China.

Shenghui Yu, Chengdu Integrated Traditional Chinese and Western Medicine Hospital/Chengdu First People's Hospital, Chengdu, China.

Maokui Yue, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China.

Chunyang Zhang, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.

Jiliang Zhang, Guilin People's Hospital, Guilin, China.

Ke Zhang, Gansu Provincial People's Hospital, Lanzhou, China.

Leibing Zhang, Guizhou Provincial People's Hospital, Guiyang, China.

Lianyang Zhang, Daping Hospital, Army Medical University, Chongqing, China.

Liang Zhang, Xuzhou First People's Hospital, Xuzhou, China.

Mao Zhang, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Ying Zhang, Heyou Hospital, Guangzhou, China.

Zhengliang Zhang, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Feng Zhao, 910th Hospital of the Joint Logistic Support Force, Quanzhou, China.

Yicheng Zheng, Lhasa People's Hospital, Lhasa, China.

Renjie Zhou, The Second Affiliated Hospital of Army Medical University, Chongqing, China.

Xiaozhong Zhou, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

Yanan Zhu, Taizhou Hospital of Zhejiang Province, Taizhou, China.

Jianchun Zong, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Ethical statement

Ethical approval and informed consent were not required because this expert consensus did not involve human participants, identifiable patient data, or animal experiments.

Funding

This work was supported by the Chongqing Science and Health Joint Project (No. 2025CCXM001). The development of this consensus did not receive funding from any commercial organization.

Declaration of competing interests

All experts who participated in the development of this consensus declare that they have no conflicts of interest. The expert voting and consensus development process was independent of any pharmaceutical enterprise or company.