Early adjunctive local block therapy improves pain and limb swelling after Gloydius envenomation: a propensity score–adjusted retrospective cohort study in the emergency department

Abstract

Background

Snakebite envenomation remains a major neglected tropical disease worldwide and frequently results in substantial local tissue injury despite timely antivenom therapy. Effective adjunctive strategies for early local symptom control are still limited. We aimed to evaluate whether early local block therapy (LBT) is associated with improved pain and limb swelling outcomes in patients with Gloydius envenomation.

Methods

We conducted a single-center retrospective cohort study including 203 adult patients with confirmed Gloydius envenomation between 2019 and 2024. Patients were categorized according to receipt of LBT (perilesional lidocaine, dexamethasone, and α-chymotrypsin) in addition to standard care. Primary outcomes were reduction in limb swelling (change in limb circumference from admission to Day 3) and pain relief (change in VAS score within 48 h). Secondary outcome was length of hospital stay (LOS). Multivariable linear regression and propensity score–based analyses were performed to adjust for potential confounders, including baseline wound infection.

Results

Baseline wound infection was more frequent in the LBT group than in controls (41.3% vs. 25.2%, P = 0.015). After full adjustment, LBT remained independently associated with greater limb swelling reduction (adjusted β = 2.31 cm; 95% CI 2.08–2.54; P < 0.001) and greater pain relief (adjusted β = 2.13 points; 95% CI 1.83–2.43; P < 0.001). Findings were consistent across propensity score–matched and weighted analyses. LBT was not associated with prolonged hospitalization (adjusted β = −0.98 days; P = 0.066).

Conclusions

In this real-world cohort, early adjunctive LBT was associated with clinically meaningful improvement in local symptoms without evidence of increased hospital stay. These findings support LBT as a potential adjunctive strategy for hemotoxic snakebite and warrant prospective validation in multicenter prospective studies.

Introduction

Snakebite envenomation is a World Health Organization–recognized neglected tropical disease that continues to impose a substantial burden on emergency care systems worldwide [1]. In addition to systemic toxicity, many patients experience pronounced local tissue injury, including progressive limb swelling and severe pain, which may persist despite appropriate antivenom therapy. Effective adjunctive interventions targeting early local symptom control remain an important yet under-studied clinical need [2–5].

While intravenous antivenom remains the cornerstone of treatment for neutralizing circulating toxins and preventing systemic mortality [1, 4, 5], its efficacy in mitigating established local tissue damage is often limited. Antivenom molecules may have restricted penetration into the poorly perfused, edematous bite site, potentially resulting in suboptimal neutralization of locally deposited venom depots. Consequently, patients often endure persistent pain and progressive limb swelling despite adequate systemic antivenom administration, leading to prolonged suffering and potential long-term sequelae [6, 7].

To address this therapeutic gap, local block therapy (LBT)—involving the perilesional injection of anesthetic and anti-inflammatory agents—has been utilized as an adjunctive intervention in clinical practice. The rationale for this multimodal approach involves three distinct theoretical mechanisms: (1) Lidocaine acts as a sodium channel blocker to inhibit nociceptive transmission and Lidocaine acts as a sodium channel blocker to inhibit nociceptive transmission and may also exert anti-inflammatory effects [8–12]. (2) Dexamethasone, a potent corticosteroid, targets the intense inflammatory cascade triggered by venom metalloproteinases and phospholipases; and (3) α-Chymotrypsin, a serine protease, is hypothesized to facilitate the reduction of inflammatory edema and potentially degrade proteinaceous venom components, although its specific efficacy in snakebite remains under-investigated in the Western literature [13, 14].

Despite its empirical use in certain East Asian medical centers, high-quality evidence regarding the efficacy and safety of LBT, particularly the inclusion of α-chymotrypsin, is lacking. Previous studies have been limited by small sample sizes or lack of rigorous adjustment for confounding factors such as disease severity. In this study, we conducted a retrospective cohort analysis using propensity score–based methods to evaluate the association between early LBT administration and local symptom relief (swelling and pain) in patients with confirmed Gloydius envenomation. Furthermore, we aimed to assess the safety of this intervention by examining its impact on hospital length of stay and the incidence of local complications.

Materials and methods

Study design and ethics

This single-center, retrospective cohort study was conducted at the Emergency Department of the Fourth Medical Center of the PLA General Hospital. We reviewed the electronic medical records of all patients admitted with snakebite envenomation between January 1, 2019, and December 31, 2024.

Patient selection

Eligible participants were adults (age ≥ 18 years) with clinically diagnosed Gloydius brevicaudus envenomation. Species identification was based on a composite standard including: (1) definitive identification of the snake specimen (when brought by the patient) by experienced herpetologists or physicians; or (2) a distinct clinical syndrome consistent with Gloydius envenomation (hemorrhagic swelling, pain, coagulopathy) combined with clear epidemiological exposure in Northern China, where G. brevicaudus is the predominant viperid species.

Exclusion criteria were: (1) presentation > 72 h after the bite; (2) pregnancy or lactation; (3) significant pre-existing coagulopathy, including therapeutic anticoagulant or antiplatelet use; and (4) incomplete documentation of primary outcome measures.

Significant pre-existing coagulopathy was defined as a known coagulation disorder unrelated to the snakebite, chronic liver disease with baseline coagulopathy, or use of anticoagulant/antiplatelet therapy before the bite. Venom-induced consumptive coagulopathy at admission was not an exclusion criterion; it was recorded as a baseline severity variable and adjusted for in statistical models.

Patients presenting more than 72 h after the bite were excluded to reduce heterogeneity related to delayed presentation, prior treatment, evolving wound complications, and variable clinical trajectories. This exclusion criterion was introduced for methodological consistency and does not imply that patients presenting later cannot experience pain or benefit from symptomatic treatment.

Pregnant or lactating patients were excluded from the analytic cohort because they represent distinct populations with specific maternal-fetal or lactation-related safety considerations. This exclusion was methodological and does not imply that analgesia or appropriate snakebite treatment should be withheld from these patients.

Treatment protocol and grouping

All patients received standard-of-care management according to institutional protocols, including tetanus prophylaxis, wound cleaning, and intravenous administration of specific Gloydius antivenom (Shanghai Serum Biological Technology Co., Ltd.).

Local Block Therapy (LBT) Group: Patients in this group received LBT in addition to standard care. The decision to administer LBT was based on the treating physician’s clinical judgment regarding local symptom severity and patient consent, rather than a randomized protocol. LBT was administered early as a standardized subcutaneous circumferential perilesional infiltration. The LBT mixture consisted of 10 mL of 0.5% plain lidocaine without adrenaline, dexamethasone 10 mg, α-chymotrypsin 4000 IU, and sterile normal saline to a final injectable volume of approximately 20 mL. The final working concentration of lidocaine was approximately 0.25%, corresponding to a total lidocaine dose of 50 mg. The infiltration volume and distribution were adjusted according to the size of the involved limb and the extent of local swelling. All LBT procedures were performed using the fine needle attached to a 1-mL syringe. Injection sites were placed approximately 2–3 cm away from the wound or visible skin lesion along the outer margin of the affected area, while avoiding direct injection into purulent points, abscesses, necrotic tissue, hemorrhagic bullae, blisters, visibly vascular areas, or the bite puncture itself. Gentle local compression and clinical observation were performed after injection.

When antivenom was indicated, antivenom preparation and administration were prioritized immediately after presentation. LBT was performed only as an adjunctive local intervention and was commonly carried out in parallel with antivenom preparation or initiation, without delaying systemic antivenom therapy.

Control Group: Patients in this group received standard care alone (antivenom + analgesics as needed) without local block therapy.

Data collection and definitions

Data were extracted from electronic medical records using a standardized case report form. Baseline demographic and clinical characteristics were collected, including age, sex, BMI, bite site, time from bite to presentation, vital signs, and laboratory parameters.

Definition of Baseline Wound Infection: Participants were included strictly if they presented within 72 h of the snakebite. Within this acute time window, distinguishing early bacterial infection from venom-induced sterile inflammation is critical. While sterile inflammation (erythema, edema) is ubiquitous in Gloydius envenomation [15], early bacterial infection observed at admission is typically associated with improper pre-hospital first aid (e.g., non-sterile incision, herbal application) or delayed presentation within the inclusion window [16].

To ensure diagnostic specificity and avoid misclassifying sterile inflammation as infection, Baseline Wound Infection was strictly defined by the presence of the following composite criteria at hospital admission:

Macroscopic Purulence: Visible purulent discharge (pus) or abscess formation at the bite site or incision wound; AND Disproportionate Leukocytosis: A white blood cell (WBC) count > 15 × 10$^9$/L (distinguishing from mild stress-induced leukocytosis common in envenomation) [17].

Patients presenting with severe swelling, hemorrhagic blistering, or local redness without purulence were classified as having sterile venom-induced inflammation, regardless of the time elapsed since the bite [15].

Outcome measures

Primary outcomes (effectiveness)

Limb Swelling Reduction: Defined as the absolute decrease in limb circumference (cm) from admission (Day 1) to Day 3. Measurements were performed using a flexible non-stretch tape at a marked anatomical landmark (e.g., 10 cm proximal to the malleolus or wrist) to ensure consistency between time points.

Pain Relief: Assessed using the Visual Analog Scale (VAS, 0–10). The outcome was defined as the reduction in VAS score from admission to 48 h post-treatment. This time point was selected to evaluate sustained analgesic effects beyond the immediate duration of lidocaine action.

Secondary outcomes (safety)

Length of Hospital Stay (LOS): Total days of hospitalization.

Local Complications: We specifically extracted data on secondary wound infection (defined by purulent discharge or positive culture requiring antibiotics) and tissue necrosis (requiring surgical debridement).

Statistical analysis

Continuous variables were expressed as mean ± standard deviation (SD) or median (IQR). Differences between groups were compared using Student’s t-test or Mann-Whitney U test. Categorical variables were compared using the Chi-square test.

Because treatment allocation was not randomized, baseline imbalances were addressed using multivariable regression and propensity score–based analyses. To address potential selection bias inherent in the observational design, we employed Propensity Score Matching (PSM). A propensity score for the likelihood of receiving LBT was calculated using a logistic regression model including age, sex, BMI, bite site, time to presentation, antivenom dose, and baseline Snakebite Severity Score (SSS). Patients were matched 1:1 using a nearest-neighbor algorithm with a caliper width of 0.2.

Outcomes were analyzed using multivariable linear regression, adjusting for potential confounders. Antivenom dose was included as a clinically relevant covariate in both the multivariable regression and propensity score models. Results are reported as regression coefficients (β) with 95% confidence intervals (CI). Model assumptions (normality of residuals and homoscedasticity) were verified visually. A two-sided P-value < 0.05 was considered statistically significant. All analyses were performed using R software (version 4.1.0; R Foundation for Statistical Computing, Vienna, Austria). This study is reported in accordance with the STROBE guidelines for observational studies.

The study protocol was approved by the Institutional Ethics Committee (Approval No. 2024KY1052-KS001). The study was conducted in accordance with the Declaration of Helsinki. The requirement for informed consent was waived due to the retrospective and anonymized nature of the study.

Results

Study population and baseline characteristics

A total of 384 patients were initially screened for eligibility. After excluding pediatric patients, those with non-Gloydius envenomation, and those presenting beyond the 72-hour window or with significant confounders, 203 patients were included in the final analysis (Fig. 1). Of these, 92 patients (45.3%) received Local Block Therapy (LBT) combined with standard care, while 111 patients (54.7%) were managed with standard care alone.

Fig. 1.

Flow diagram of patient selection and exclusion

Baseline demographic and clinical characteristics are summarized in Table 1. The two groups were comparable regarding age, sex, body mass index (BMI), bite site, and baseline Snakebite Severity Score (SSS). However, significant differences were observed in baseline wound characteristics. The prevalence of baseline wound infection—strictly defined by the presence of purulence and marked leukocytosis—was significantly higher in the LBT group compared to the control group (41.3% vs. 25.2%, P = 0.015). This suggests that treating physicians were more inclined to administer local block therapy to patients with distinct signs of local infection. Additionally, patients in the LBT group presented to the hospital significantly earlier (11.2 ± 10.8 h vs. 19.6 ± 18.6 h, P < 0.001) but had lower baseline C-reactive protein levels (5.0 ± 5.9 mg/L vs. 9.9 ± 17.7 mg/L, P = 0.012). These baseline imbalances were accounted for in all subsequent multivariable and propensity score–based analyses.

Table 1.

Baseline characteristics and unadjusted outcomes of patients according to receipt of local block therapy

Variable	Total (N = 203)	Standard Care (N = 111)	Local Block Therapy (N = 92)	P Value
Age (years), Mean ± SD	45.8 ± 14.4	45.7 ± 15.1	46.0 ± 13.6	0.861
Sex, n (%)				0.71
Male	122 (60.1)	68 (61.3)	54 (58.7)
Female	81 (39.9)	43 (38.7)	38 (41.3)
BMI (kg/m²), Mean ± SD	24.0 ± 3.7	23.8 ± 3.6	24.1 ± 3.9	0.536
Bite Site, n (%)				0.343
Upper extremity	114 (56.2)	59 (53.2)	55 (59.8)
Lower extremity	89 (43.8)	52 (46.8)	37 (40.2)
Time to presentation (hours)	15.8 ± 16.1	19.6 ± 18.6	11.2 ± 10.8	< 0.001
Snakebite Severity Score, n (%)				0.178
Mild	125 (61.6)	73 (65.8)	52 (56.5)
Moderate-to-Severe	78 (38.4)	38 (34.2)	40 (43.5)
Clinical Treatment
Antivenom received, n (%)	203 (100.0)	111 (100.0)	92 (100.0)	–
Antivenom dose (vials), Mean ± SD	1.28 ± 0.68	1.22 ± 0.51	1.35 ± 0.84	0.193
VICC at admission, n (%)	58 (28.6)	29 (26.1)	29 (31.5)	0.397
Baseline Wound Infection, n (%)	66 (32.5)	28 (25.2)	38 (41.3)	0.015
Laboratory Parameters
WBC (× 10$^9$/L)	13.1 ± 5.5	12.5 ± 5.0	13.8 ± 6.0	0.075
CRP (mg/L)	7.7 ± 13.9	9.9 ± 17.7	5.0 ± 5.9	0.012
NLR	10.8 ± 11.2	9.7 ± 9.4	12.1 ± 13.0	0.129
Outcomes (Unadjusted)
Length of stay (days)	5.9 ± 3.7	6.2 ± 4.5	5.4 ± 2.4	0.144
Limb swelling reduction (cm)	1.9 ± 1.4	0.8 ± 0.7	3.1 ± 0.8	< 0.001
Pain score reduction (VAS)	2.4 ± 1.5	1.3 ± 0.8	3.6 ± 1.2	< 0.001

Data are presented as mean ± standard deviation or number (%), as appropriate

Unadjusted outcomes are presented for descriptive purposes only; adjusted associations between local block therapy and clinical outcomes are reported separately using multivariable regression and propensity score–based analyses

Abbreviations: LBT, local block therapy; BMI, body mass index; SSS, Snakebite Severity Score; VICC, venom-induced consumptive coagulopathy; WBC, white blood cell count; CRP, C-reactive protein; NLR, neutrophil-to-lymphocyte ratio; ASV, antivenom serum

Univariable logistic regression analysis (Table 2) identified three factors significantly associated with the receipt of LBT. Consistent with clinical observations, baseline wound infection was significantly associated with a higher likelihood of receiving LBT (OR 2.09; 95% CI 1.15–3.79; P = 0.016). Conversely, delayed presentation was associated with a lower likelihood of receiving therapy (OR 0.96 per hour delay; P = 0.001), and higher baseline CRP levels were negatively associated with LBT administration (OR 0.96; P = 0.022).

Table 2.

Univariable logistic regression analysis of factors associated with the receipt of local block therapy

Variable	Odds Ratio (95% CI)	P Value
Time to presentation (hours)	0.96 (0.94–0.98)	0.001
Baseline CRP (mg/L)	0.96 (0.93–0.99)	0.022
Baseline Wound Infection (Yes vs. No)	2.09 (1.15–3.79)	0.016
Age (years)	1.00 (0.98–1.02)	0.86
Male Sex (vs. Female)	0.90 (0.51–1.58)	0.71
BMI (kg/m²)	1.02 (0.95–1.10)	0.534
Bite Site (Lower vs. Upper Extremity)	0.76 (0.44–1.34)	0.344
Snakebite Severity Score
Moderate-Severe vs. Mild	1.36 (0.76–2.45)	0.298
VICC at admission (Yes vs. No)	1.30 (0.71–2.40)	0.397
WBC Count	1.05 (0.99–1.10)	0.077
Neutrophil-to-Lymphocyte Ratio	1.02 (0.99–1.05)	0.14

Note: CI, confidence interval; VICC, venom-induced consumptive coagulopathy; CRP, C-reactive protein; WBC, white blood cell. Interpretation: An odds ratio > 1 indicates a higher likelihood of receiving local block therapy

Effectiveness of local block therapy

Limb Swelling Reduction Local block therapy was independently associated with a greater reduction in limb swelling. In the unadjusted analysis, the mean reduction in limb circumference from Day 1 to Day 3 was 2.29 cm greater in the LBT group compared with the control group (95% CI 2.08–2.50; P < 0.001). This association remained robust in the fully adjusted multivariable linear regression model (Model V), which accounted for potential confounders including age, sex, BMI, SSS, time to presentation, antivenom dose, and inflammatory markers (adjusted β = 2.31 cm; 95% CI 2.08–2.54; P < 0.001; Table 3).

Table 3.

Association between local block therapy and reduction in limb swelling (Multivariable Linear Regression)

Model	Coefficient (β) (95% CI)	P Value
Model I (Unadjusted)	2.31 (2.00–2.54)	< 0.001
Model II	2.30 (2.08–2.51)	< 0.001
Model III	2.30 (2.07–2.53)	< 0.001
Model IV	2.31 (2.08–2.54)	< 0.001
Model V (Fully Adjusted)	2.31 (2.08–2.54)	< 0.001

Note: The coefficient (β) represents the additional reduction in limb circumference (cm) in the local block therapy group compared with the standard care group

Model I: Unadjusted

Model II: Adjusted for age, sex, and BMI

Model III: Model II plus wound infection, bite site, time to presentation, and antivenom dose

Model IV: Model III plus Snakebite Severity Score

Model V: Model IV plus inflammatory markers (WBC, CRP, NLR)

Pain Relief Patients receiving LBT experienced superior early pain relief. The reduction in VAS pain scores at 48 h was significantly greater in the LBT group compared with standard care after adjustment for the same covariates, including antivenom dose (adjusted β = 2.13 points; 95% CI 1.83–2.43; P < 0.001; Table 4).

Table 4.

Association between local block therapy and pain relief (Multivariable Linear Regression)

Model	Coefficient (β) (95% CI)	P Value
Model I (Unadjusted)	2.28 (2.00–2.56)	< 0.001
Model II	2.27 (1.99–2.55)	< 0.001
Model III	2.16 (1.87–2.45)	< 0.001
Model IV	2.15 (1.86–2.44)	< 0.001
Model V (Fully Adjusted)	2.13 (1.83–2.43)	< 0.001

Note: The coefficient (β) represents the additional reduction in VAS pain score (points) in the local block therapy group compared with the standard care group. * Models are adjusted for the same covariates as described in Table 3

Sensitivity analyses using propensity score matching (PSM), inverse probability of treatment weighting (IPTW), standardized mortality ratio weighting (SMRW), and overlap weighting consistently supported this finding, with effect estimates ranging from 2.29 to 2.40 cm for limb swelling reduction (all P < 0.001; Table 5) and from 2.15 to 2.26 points for pain relief (all P < 0.001; Table 6).

Table 5.

Sensitivity analyses for pain relief (Propensity Score Methods)

Statistical Method	Effect Estimate (95% CI)	P Value
Unadjusted Analysis	2.28 (1.99–2.56)	< 0.001
Multivariable Regression Adjustment	2.17 (1.87–2.46)	< 0.001
Propensity Score Adjustment	2.15 (1.86–2.45)	< 0.001
Propensity Score Matching (1:1)	2.26 (1.93–2.60)	< 0.001
Inverse Probability of Treatment Weighting (IPTW)	2.14 (1.87–2.41)	< 0.001
Standardized Mortality Ratio Weighting (SMRW)	2.20 (1.92–2.48)	< 0.001
Overlap Weighting	2.15 (1.88–2.43)	< 0.001

Note: Effect estimate refers to the mean difference in VAS pain score reduction between the LBT and standard care groups

Table 6.

Association between local block therapy and length of hospital stay

Variable	Coefficient (β) (95% CI)	P Value
Standard Care (Reference)	—	—
Local Block Therapy (Unadjusted)	-0.76 (-1.78 to 0.26)	0.144
Local Block Therapy (Adjusted) **	-0.98 (-2.02 to 0.06)	0.066

Note: β indicates the difference in hospital stay (days). * *Adjusted for age, sex, BMI, Snakebite Severity Score, time to presentation, bite site, antivenom dose, and baseline VICC status

Safety assessment (Length of Hospital Stay)

To assess the clinical safety of the intervention, we evaluated the length of hospital stay (LOS) as a composite surrogate for potential complications. The administration of Local Block Therapy (LBT) was not associated with a prolongation of hospitalization. In the unadjusted analysis, the LOS was comparable between the LBT and control groups (5.4 ± 2.4 vs. 6.2 ± 4.5 days, P = 0.144).

After multivariable adjustment, LBT was associated with a numerically shorter length of stay, although this difference did not reach statistical significance (adjusted β = -0.98 days; 95% CI -2.02 to 0.06; P = 0.066). No immediate injection-site hematoma or clinically significant bleeding was observed after the procedure, and no delayed clinically significant injection-site hematoma requiring intervention was documented during hospitalization. These findings suggest that the early administration of LBT did not result in clinically significant adverse events that would otherwise necessitate extended hospitalization.

Discussion

In this propensity score–adjusted retrospective cohort study, early adjunctive local block therapy was consistently associated with improved short-term control of limb swelling and pain following Gloydius envenomation. Importantly, these benefits were observed without evidence of prolonged hospitalization, supporting the potential clinical utility of LBT as an adjunct to standard antivenom therapy in the emergency setting [13].

Globally, antivenom remains the cornerstone of treatment for snakebite envenomation and is essential for preventing or reversing systemic venom effects. However, persistent local tissue injury, swelling, pain, and functional impairment remain challenging clinical problems, particularly after viperid envenomation. Previous global studies and reviews have highlighted that local tissue damage may remain difficult to control once inflammation, edema, and microvascular injury have become established. In this context, our study provides real-world clinical evidence suggesting that early adjunctive LBT may improve short-term local symptom control. Nevertheless, these findings should be interpreted as hypothesis-generating and complementary to antivenom therapy rather than as evidence supporting replacement of standard systemic treatment.

Interpretation of Effectiveness in the Context of Selection Bias A unique finding of our study was the significantly higher prevalence of baseline wound infection (defined by purulence and marked leukocytosis) in the LBT group compared to the control group (41.3% vs. 25.2%). This reflects “confounding by indication,” where clinicians preferentially utilized aggressive local therapy for patients presenting with more complicated local wounds. Typically, infected wounds are associated with persistent inflammation and slower resolution of edema. However, our multivariable and propensity score–matched models revealed that, even after adjusting for this unfavorable baseline characteristic, LBT recipients achieved superior symptom relief. This suggests that the therapeutic effect of LBT is robust and may be particularly valuable in high-risk patients with intense local inflammatory responses.

Pharmacological Rationale and Mechanisms The components of the LBT “cocktail” address distinct pathophysiological pathways of Gloydius envenomation, which is characterized by metalloproteinase-induced tissue destruction, myonecrosis, and intense inflammation [3, 18, 19].

Lidocaine: While previous concerns have been raised regarding the reduced efficacy of local anesthetics in the acidic environment of inflamed tissue, our results demonstrate significant clinical analgesic benefit. Lidocaine likely acts not only by blocking sodium channels to inhibit nociception but also by modulating neurogenic inflammation, inflammatory mediator release, and local microvascular perfusion, which may contribute to reduction of ischemic and inflammatory pain. Although longer-acting local anesthetics such as levobupivacaine may theoretically provide more prolonged analgesia, lidocaine was used in the present protocol because of its rapid onset, wide availability, and established use in our emergency department. Levobupivacaine was not part of our routine LBT regimen during the study period; therefore, comparative evaluation of different local anesthetics was beyond the scope of this retrospective study and should be addressed in future prospective trials.The sustained pain improvement observed at 48 h is unlikely to be explained solely by the short pharmacologic duration of lidocaine and may reflect interruption of early pain–inflammation amplification and modulation of local inflammatory edema.

Dexamethasone: The early administration of corticosteroids targets the arachidonic acid cascade, suppressing the release of inflammatory mediators (e.g., cytokines, prostaglandins) triggered by venom phospholipases [18, 19]. This aligns with previous studies suggesting that short-term steroids can reduce snakebite-induced limb edema without compromising venom neutralization [6, 14, 20]. In our institutional LBT protocol, dexamethasone was selected because of its rapid anti-inflammatory effect, water solubility, and routine availability in emergency care. The protocol was intended for acute-phase local symptom control rather than prolonged depot steroid exposure; therefore, depot corticosteroids such as triamcinolone were not used. Although debate remains regarding the role of corticosteroids in snakebite management [21], our findings suggest that dexamethasone-containing LBT may have potential utility as a selected adjunctive local strategy in Gloydius envenomation.

α-Chymotrypsin: The inclusion of this serine protease is less common in Western practice but is utilized in East Asian settings to facilitate the resolution of inflammatory edema. Drawing from animal models of enzyme therapy in envenomation [7]. we hypothesize that α-chymotrypsin may aid in the proteolytic clearance of fibrin depots and inflammatory debris in the interstitial space, thereby reducing tissue oncotic pressure and promoting fluid resorption. Unlike hyaluronidase, which is known to facilitate venom spread, α-chymotrypsin was not associated with increased systemic toxicity (VICC) or prolonged hospitalization in our cohort.

Safety considerations

A theoretical concern regarding local injection therapies is the potential to increase intracompartmental pressure or facilitate the systemic spread of venom components. Our data provide reassurance regarding these risks. The length of hospital stay—a composite proxy for recovery trajectory and complications—was not prolonged in the LBT group (Table 7). This suggests that the “ring block” technique did not induce clinically significant iatrogenic injury, secondary infection, or extensive necrosis requiring prolonged care, consistent with findings in other local block studies for snakebite [13]. The lack of adverse safety signals supports the use of LBT as a safe adjunctive measure when performed under sterile conditions.

Table 7.

Sensitivity analyses for limb swelling reduction (Propensity Score Methods)

Statistical Method	Effect Estimate (95% CI)	P Value
Unadjusted Analysis	2.29 (2.08–2.51)	< 0.001
Multivariable Regression Adjustment	2.36 (2.13–2.58)	< 0.001
Propensity Score Adjustment	2.29 (2.13–2.58)	< 0.001
Propensity Score Matching (1:1)	2.40 (2.15–2.65)	< 0.001
Inverse Probability of Treatment Weighting (IPTW)	2.33 (2.12–2.54)	< 0.001
Standardized Mortality Ratio Weighting (SMRW)	2.32 (2.10–2.53)	< 0.001
Overlap Weighting	2.35 (2.14–2.57)	< 0.001

note: Effect estimate refers to the mean difference in limb circumference reduction (cm) between the LBT and standard care groups

It should also be noted that this study does not establish LBT as superior to systemic or oral anti-inflammatory therapy. Oral corticosteroids may be an alternative approach, particularly when bleeding risk is a concern. In our setting, LBT was used to provide rapid local analgesia and local anti-inflammatory modulation in patients with rapidly progressive swelling and severe pain. Therefore, LBT should be interpreted as an adjunctive local intervention rather than a replacement for systemic or oral therapy. Future prospective comparative studies are needed to evaluate local and systemic anti-inflammatory strategies and safety in patients with different degrees of coagulopathy.

Limitations

Several limitations must be acknowledged. First, the retrospective, non-randomized design introduces inherent selection bias. Although we employed propensity score matching and multivariable regression to adjust for confounders, including the higher baseline infection rate in the treatment group, residual unmeasured confounding may persist. Exact minute-level timing between antivenom initiation and LBT was not consistently available in the retrospective records. However, institutional practice prioritized immediate antivenom preparation and initiation, with LBT performed only as an adjunctive intervention without delaying systemic therapy. Second, the diagnosis of baseline wound infection relies on clinical records. To minimize misclassification of sterile venom-induced inflammation as infection, we applied a strict composite definition requiring macroscopic purulence plus marked leukocytosis [15]. Procalcitonin was not routinely measured in all patients and therefore could not be incorporated into the definition of baseline wound infection or adjusted analyses. Although this approach improved specificity, milder infections may have been overlooked, and potential misclassification between bacterial infection and venom-induced sterile inflammation cannot be completely excluded. Furthermore, early infections in our cohort were likely associated with improper pre-hospital first aid practices common in the region [16] which warrants further public health education. Third, we used the length of hospital stay as a surrogate for safety outcomes; detailed data on necrotic volume or long-term functional recovery were not available for all patients. Finally, because this study included only patients with Gloydius envenomation, the findings should not be directly extrapolated to other snakebite syndromes, including elapid envenomation, in which venom composition, dominant clinical manifestations, and local tissue effects may differ.

Conclusions

In summary, Local Block Therapy is associated with significant early improvement in swelling and pain in patients with Gloydius envenomation. This association remains robust even after adjusting for the baseline infection burden and other potential confounders. LBT may be considered as a selected adjunctive strategy for short-term symptom control when performed away from infected, necrotic, or blistered tissue and under appropriate safety precautions. It should not be considered a substitute for antivenom, wound care, or infection management. Future prospective studies are needed to validate these findings and further define the safety criteria for LBT in pit viper envenomation.

Author contributions

Hong-sheng Liu conceived and designed the study. Liang Shan, Jian-bo Zhang, and Li Yan collected the data. Liang Shan performed the statistical analysis and drafted the manuscript. Jian-bo Zhang and Li Yan contributed to data interpretation and critically revised the manuscript. Jun Yu and Li-li Cheng assisted with data validation and methodological review. Hong-sheng Liu supervised the study and provided critical revisions. All authors read and approved the final manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Data availability

Our data can be accessed by contacting the corresponding author.

Declarations

Competing interests

The authors declare no competing interests.