A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan

Jen-Yu Hsu; Shu-O Chiang; Chen-Chang Yang; Yan-Chiao Mao

doi:10.4269/ajtmh.24-0030

. 2024 May 7;111(1):205–215. doi: 10.4269/ajtmh.24-0030

A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan

Jen-Yu Hsu ^1,^2,³, Shu-O Chiang ⁴, Chen-Chang Yang ^1,^2,⁵, Yan-Chiao Mao ^6,^7,^8,^9,^*

^¹Department of Occupational Medicine and Clinical Toxicology, Taipei Veterans General Hospital, Taipei, Taiwan;

^²School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan;

^³Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan;

^⁴ESTAT Statistical Consulting Co., Ltd, Taipei, Taiwan;

^⁵Institute of Environmental and Occupational Health Sciences, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan;

^⁶PhD Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;

^⁷School of Medicine, National Defense Medical Center, Taipei, Taiwan;

^⁸Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan;

^⁹Division of Clinical Toxicology, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

Financial support: This research was partly funded by the National Science and Technology Council (MOST 110-2320-B-075A-001) and Taichung Veterans General Hospital Research Funding (TCVGH-1067205C; TCVGH-1127201B), with Y.-C. Mao as the grantee. The funders had no involvement in the design of the study, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosures: Approval for this study was obtained from the Institutional Review Board of the Clinical Ethics Committee, Taichung Veterans General Hospital (CE16258B). Given the study’s retrospective design, the requirement for informed consents was waived. Measures were taken to ensure the confidentiality of medical records, safeguarding the rights and privacy of patients. Informed consent was not applicable. All relevant data are within the manuscript and its supporting information files.

Authors’ contributions: Conceptualization: J.-Y. Hsu, C.-C. Yang, Y.-C. Mao. Methodology: all authors. Investigation: J.-Y. Hsu, S.-O. Chiang. Data analysis: J.-Y. Hsu, S.-O. Chiang. Writing—original draft preparation: J.-Y. Hsu, Y.-C. Mao. Writing—review and editing: J.-Y. Hsu, Y.-C. Mao. All authors read and agreed to the published version of the manuscript.

Authors’ addresses: Jen-Yu Hsu, Department of Occupational Medicine and Clinical Toxicology, Taipei Veterans General Hospital, Taipei, Taiwan, E-mail: b94401012@ntu.edu.tw. Shu-O Chiang, ESTAT Statistical Consulting Co., Ltd, Taipei, Taiwan, E-mail: sophie@estat.com.tw. Chen-Chang Yang, Institute of Environmental and Occupational Health Sciences, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, E-mail: ccyang@vghtpe.gov.tw. Yan-Chiao Mao, Division of Clinical Toxicology, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, E-mail: doc1385e@gmail.com.

Address correspondence to Yan-Chiao Mao, Division of Clinical Toxicology, Department of Emergency Medicine, Taichung Veterans General Hospital; No. 1650, Sec. 4, Taiwan Blvd., Xitun Dist., Taichung City 407, Taiwan. E-mail: doc1385e@gmail.com

PMCID: PMC11229656 PMID: 38714189

ABSTRACT.

In Taiwan, six medically important venomous snakes, Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, Daboia siamensis, Naja atra, and Bungarus multicinctus, are found. However, comprehensive research on the complications and associated healthcare costs of snakebite envenomation (SBE) is lacking. We retrospectively analyzed pertinent information from the Taiwan National Health Insurance Research Database dated January 2002 to December 2014. We investigated the risk factors for complications and their impact on healthcare costs. Among the 12,542 patients with SBE, those from N. atra or B. multicinctus were more likely to experience wound infections and neurological complications than were those from T. s. stejnegeri or P. mucrosquamatus. In addition, being female, being elderly, and having a Charlson Comorbidity Index equal to or greater than 3 points were associated with an increased likelihood of wound infections and psychological complications. The annual national economic burden averaged US$1,083,624, with an average healthcare cost of US$1,129 per SBE. Snakebite envenomations from N. atra or B. multicinctus, as well as various complications, resulted in significantly higher costs. It is crucial to comprehend the risk factors for complications and their role in increasing expenses to provide insight for tailored healthcare interventions, mitigate complications, and reduce the economic burdens associated with SBEs.

INTRODUCTION

In 2017, the WHO reclassified snakebite envenomation (SBE) as a neglected tropical disease.¹ Because of the diverse nature of snake venoms, varying both between different species and within the same species, the acute and chronic complications of SBEs range widely.²^–⁵ Therapy with the corresponding antivenom and diligent medical care impose significant healthcare costs.⁶^,⁷ In Taiwan, effective SBE management has contributed to a low case fatality rate.⁸ Antivenom-induced anaphylaxis is rarer in Taiwan than in other Asian countries.⁸^,⁹ However, national and long-term research on the complications of SBE, such as psychological complications,¹⁰^,¹¹ and on the associated medical expenses⁸^,¹² is limited.

Six medically important venomous snakes inhabit Taiwan: Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, and Daboia siamensis in the Viperidae family and Naja atra and Bungarus multicinctus in the Elapidae family. Viperidae venoms contain enzymes that can cause local tissue injuries, resulting in symptoms and signs such as swelling, pain, blistering, bruising, and necrosis.¹³^–¹⁵ In some cases, Viperidae venoms can adversely affect the coagulation system, platelet function, and vascular integrity, potentially causing thrombotic or hemorrhagic complications, including stroke and acute kidney injury.⁴^,¹⁶^–¹⁹ On the other hand, Elapidae venoms paralyze prey by blocking acetylcholine receptors or destroying axon terminals.²⁰^–²³ Snakebite envenomation from B. multicinctus is associated with muscle paralysis and respiratory failure in humans.²⁴ In contrast, SBE from N. atra causes extensive tissue necrosis and secondary infection but insignificant neurotoxicity in humans.²⁵^,²⁶

The economic effects of SBE and its complications are a major concern with regard to allocating medical resources.²⁷ The average cost of treating SBE varies widely across countries, ranging from US$4 to US$40,000; direct healthcare expenses such as antivenom, antibiotics, pain medications, and hospitalization account for approximately 65–77% of the total cost.⁶ In Taiwan, patients with SBEs receive an average of three vials of antivenom,⁸ each vial priced at US$250; this provides an approximate estimate of the partial expenses. Patients envenomed by N. atra or B. multicinctus require more antivenom doses than do those envenomed by T. s. stejnegeri or P. mucrosquamatus.⁸ In addition, for many patients envenomed by N. atra or B. multicinctus and those who experience severe SBE complications, hospitalization is often extended,²⁸^–³³ which further increases healthcare costs.

In this nationwide study, we investigated and compared both the complications associated with SBE and/or antivenom administration among patients who received various types of antivenom and the associated healthcare costs. We aimed to comprehend the risk factors for complications and their role in expenses to provide insight for tailored healthcare interventions, mitigate complications, and reduce the economic burdens associated with SBEs.

MATERIALS AND METHODS

Patient and public involvement.

Neither patients nor the public was involved in the design, conduct, reporting, or dissemination plans of our research.

Study population and data collection.

For this retrospective study, we used data from the Taiwan National Health Insurance (NHI) Research Database that covered the period from January 2002 to December 2014. The NHI system provides uniform insurance coverage to the entire population. Within the NHI Research Database, each diagnosis, procedure, and medication is assigned a unique code from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), or from the ICD, Tenth Revision, and associated healthcare costs are documented meticulously.

The Taiwan Centers for Disease Control distributed four distinct types of ammonium sulfate–precipitated and lyophilized F(ab′)₂ fragment antivenom, each tailored to treat envenomation caused by specific snakes. These antivenom types include bivalent antivenom for T. s. stejnegeri and P. mucrosquamatus (FH) and for N. atra and B. multicinctus (FN) and monovalent antivenom for D. siamensis (FA) and for D. acutus (FD).³⁴ Patients received these antivenoms exclusively through the NHI system. Although FH, FN, and FA were available throughout the period from 2002 to 2014, FD was accessible only in 2008 and later.³⁴ For this study, we gathered comprehensive data on individuals who had received FH, FN, FA, or FD between 2002 and 2014. These data included information about their demographics, diagnoses (including complications), procedures, medications, and healthcare costs submitted to the NHI by hospitals.

Patient demographics, as previously defined,⁸ included sex, age, Charlson Comorbidity Index (CCI) score, date of antivenom administration, geographic region of the hospital providing treatment, and patient occupation. Age categories were defined as underage (<18 years of age), adults (18–65 years of age), and elderly (>65 years of age). Months in which the SBE occurred were grouped into seasons: spring (March, April, May), summer (June, July, August), autumn (September, October, November), and winter (December, January, February). Geographic regions were categorized as northern, central, southern, and eastern, and occupations were classified as agricultural workers, laborers, and others.⁸

Definitions of SBE complications.

A single SBE episode was defined as a case treated within 90 days from the administration of the initial antivenom dose.⁸ Snakebite envenomation can result in direct effects such as immunological reactions, local tissue damage, coagulopathy, nephrotoxicity, and neuroparalysis, leading to subsequent complications. All complications were recorded if the associated ICD-9-CM diagnostic codes were present (including mainly 296, 300, 311, 345, 431, 434, 518, 681, 682, 686, 728, 785, and 995). After an SBE diagnosis, the practice of administering epinephrine prior to antivenom administration was not routinely followed in Taiwan. Anaphylaxis was identified when epinephrine was prescribed within 1 day after the first antivenom dose owing to the diagnosis of shock, bronchospasm, or angioedema.³⁵^–³⁸ The physician diagnosed wound infections, such as erysipelas, cellulitis, abscess, infectious myositis, or necrotizing fasciitis that had developed within 7 days of the SBE,³⁹ and the use of antibiotics during this period was also recorded. Surgical interventions included procedures such as incisions, divisions, excisions, debridements, transplantations, reconstructions, engraftments, or amputations within 14 days of the SBE. Neurological complications included stroke, paralysis, peripheral neuropathy, hypoxic encephalopathy, or seizure within 30 days of the SBE. Endotracheal intubation referred to the use of invasive mechanical ventilation within 7 days of the SBE. Psychological complications included anxiety (such as posttraumatic stress disorder) or depression that developed within 180 days of the SBE. Hospitalization or interhospital transfer during the first 7 days of treatment was considered related to SBE. Healthcare costs were defined as the total expenses for emergency room visits, hospitalization, and outpatient care within 90 days of the SBE.

STATISTICAL ANALYSES

Complications and interventions were calculated as numbers and percentages. To evaluate the relationship between variables and these outcomes, we used either the χ² test or the two-tailed Fisher’s exact test. We constructed a logistic regression model to identify factors associated with complications and interventions. Healthcare costs were calculated as both medians and means. To explore the association between variables and healthcare costs, we used the Mann–Whitney U test. A log-linear regression model, suitable for non-normally distributed data, was constructed to analyze factors contributing to healthcare costs. Variables that had a two-sided P-value ≤0.05 in the univariable analysis were subsequently included in the final multivariable analysis, in which we used a stepwise approach to adjust for potential confounders. Regardless of their statistical significance, sex, age, and CCI score were incorporated into the final model. All statistical evaluations were conducted with Statistical Analysis Software v. 9.4 (SAS Institute, Cary, NC).

RESULTS

Study population. The study population was a subset of that of a previous study⁸; this study encompassed a total of 12,542 patients, of whom 70.1% (8,791) were male and 28.3% (3,544) were female. The median age was 53 years. The CCI scores were 0 for 25.5% (3,196) of patients, 1 for 20.5% (2,565), 2 for 16.0% (2,009), and 3 or higher for 38.0% (4,772). Antivenoms were administered as follows: 73.3% (9,194) of patients received FH alone, 17.1% (2,150) received FN alone, 0.6% (81) received FA alone, 0.1% (11) received FD alone, and 8.8% (1,106) received a mixture of different antivenoms.

Anaphylaxis.

Three percent (370) of the patients were prescribed epinephrine, and anaphylaxis was diagnosed in only 0.1% (17).⁸ We found no significant correlation between the type of antivenom administered and the occurrence of anaphylaxis (Table 1).

Table 1.

The univariable and multivariable analyses of factors associated with anaphylaxis (N = 12,542)

Variable	Anaphylaxis		No Anaphylaxis		P_a-Value^*	Univariable Analysis		Multivariable Analysis
Variable	No.	%	No.	%	P_a-Value^*	Crude Odds Ratio (95% CI)	P_b-Value^†	Adjusted Odds Ratio (95% CI)	P_c-Value^‡
All Cases	17	0.1	12,525	99.9	–	–	–	–	–
Males	11	0.1	8,780	99.9	0.3818	0.78 (0.29–2.12)	0.6281	0.68 (0.25–1.89)	0.4625
Age
<18 Years	0	0.0	459	100.0	0.6829	–	–	–	–
18–64 Years	12	0.1	8,946	99.9	–	–	–	–	–
≥65 Years	5	0.2	3,120	99.8	–	–	–	–	–
Charlson Comorbidity Index Score
0	4	0.1	3,192	99.9	0.8857	1.00 (reference)	–	1.00 (reference)	–
1	3	0.1	2,562	99.9	–	0.93 (0.21–4.18)	0.9293	0.81 (0.18–3.73)	0.7916
2	2	0.1	2,007	99.9	–	0.80 (0.15–4.35)	0.7914	0.75 (0.14–4.13)	0.7386
≥3	8	0.2	4,764	99.8	–	1.34 (0.40–4.45)	0.6329	1.07 (0.31–3.63)	0.9195
Types of Antivenom^§
FH	13	0.1	9,181	99.9	0.8044	1.00 (reference)	–	–	–
FN	2	0.1	2,148	99.9	–	0.66 (0.15–2.92)	0.5812	–	–
FH + FN	2	0.2	965	99.8	–	1.46 (0.33–6.5)	0.6163	–	–
Others	0	0.0	231	100.0	–	–	0.9867	–	–
Season
Spring	10	0.3	2,905	99.7	0.0032	1.00 (reference)	–	1.00 (reference)	–
Summer	1	0.0	4,498	100.0	–	0.06 (0.01–0.50)	0.0090	0.06 (0.01–0.47)	0.0075
Fall	5	0.1	3,934	99.9	–	0.37 (0.13–1.08)	0.0692	0.40 (0.14–1.20)	0.1015
Winter	1	0.1	1,188	99.9	–	0.24 (0.03–1.91)	0.1795	0.25 (0.03–1.98)	0.1880
Endotracheal Intubation	4	4.8	79	95.2	<0.0001	48.5 (15.48–151.97)	<0.0001	55.86 (17.13–182.13)	<0.0001

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P_a-value: the χ² or two-tailed Fisher’s exact test.

^{^†}

P_b-value: univariable analysis using the logistic regression model.

^{^‡}

P_c-value: multivariable analysis using the logistic regression model.

^{^§}

FH = a bivalent antivenom against Trimeresurus stejnegeri stejnegeri and Protobothrops mucrosquamatus; FN = a bivalent antivenom against Naja atra and Bungarus multicinctus; Others = including an antivenom against Deinagkistrodon acutus, an antivenom against Daboia siamensis, and mixed antivenoms except FH and FN.

Wound infections and necrotizing fasciitis. Among the entire patient cohort, wound infections, diagnosed by physicians, developed in 21.7% (2,716), whereas necrotizing fasciitis was diagnosed in 1.7% (217).⁸ Among the 9,194 who received FH, wound infections developed in 20.3% (1,862) and necrotizing fasciitis in 0.6% (56). In contrast, among the 2,150 FN recipients, these rates were higher: wound infections developed in 23.4% (503) and necrotizing fasciitis in 4.8% (104). Patients who received FN thus had 1.2 times higher odds of wound infection (95% CI: 1.1–1.3; P = 0.0036) and 7.8 times higher odds of necrotizing fasciitis (95% CI: 5.6–11.0; P <0.0001) than those who received FH.⁸ Wound infections and necrotizing fasciitis were more likely to occur in female patients, during the summer or autumn, and in patients who received epinephrine (Tables 2 and 3).

Table 2.

The univariable and multivariable analyses of factors associated with wound infections (N = 12,542)

Variable	Wound Infections		No Wound Infections		P_a-Value^*	Univariable Analysis		Multivariable Analysis
Variable	No.	%	No.	%	P_a-Value^*	Crude Odds Ratio (95% CI)	P_b-Value^†	Adjusted Odds Ratio (95% CI)	P_c-Value^‡
All Cases	2,716	21.7	9,826	78.3	–	–	–	–	–
Males	1,815	20.6	6,976	79.4	0.0001	0.82 (0.75–0.90)	<0.0001	0.83 (0.76–0.92)	0.0001
Age
<18 Years	86	18.7	373	81.3	0.0043	1.00 (reference)	–	1.00 (reference)	–
18–64 Years	1,892	21.1	7,066	78.9	–	1.16 (0.91–1.48)	0.2217	1.14 (0.89–1.46)	0.2853
≥65 Years	738	23.6	2,387	76.4	–	1.34 (1.05–1.72)	0.0207	1.37 (1.05–1.78)	0.0205
Charlson Comorbidity Index
0	641	20.1	2,555	79.9	0.0033	1.00 (reference)	–	1.00 (reference)	–
1	551	21.5	2,014	78.5	–	1.09 (0.96–1.24)	0.1845	1.11 (0.97–1.26)	0.1299
2	413	20.6	1,596	79.4	–	1.03 (0.90–1.18)	0.6614	1.03 (0.90–1.19)	0.6665
≥3	1,111	23.3	3,661	76.7	–	1.21 (1.08–1.35)	0.0007	1.20 (1.06–1.35)	0.0030
Types of Antivenom^§
FH	1,862	20.3	7,332	79.7	<0.0001	1.00 (reference)	–	1.00 (reference)	–
FN	503	23.4	1,647	76.6	–	1.20 (1.08–1.35)	0.0013	1.19 (1.06–1.34)	0.0036
FH + FN	294	30.4	673	69.6	–	1.72 (1.49–1.99)	<0.0001	1.61 (1.39–1.87)	<0.0001
Others	57	24.7	174	75.3	–	1.29 (0.95–1.75)	0.1001	1.26 (0.93–1.72)	0.1347
Season
Spring	585	20.1	2,330	79.9	0.0601	1.00 (reference)	–	1.00 (reference)	–
Summer	978	21.7	3,521	78.3	–	1.11 (0.99–1.24)	0.0852	1.07 (0.96–1.21)	0.2314
Fall	898	22.8	3,041	77.2	–	1.18 (1.05–1.32)	0.0067	1.18 (1.05–1.33)	0.0058
Winter	255	21.4	934	78.6	–	1.09 (0.92–1.28)	0.3210	1.14 (0.96–1.35)	0.1247
Region
Northern	984	22.7	3,342	77.3	<0.0001	1.00 (reference)	–	1.00 (reference)	–
Central	489	26.2	1,374	73.8	–	1.21 (1.07–1.37)	0.0030	1.18 (1.04–1.35)	0.0135
Southern	645	20.0	2,573	80.0	–	0.85 (0.76–0.95)	0.0048	0.87 (0.77–0.98)	0.0207
Eastern	598	19.1	2,537	80.9	–	0.80 (0.71–0.90)	0.0001	0.82 (0.73–0.92)	0.0007
Occupation
Agricultural Worker	1,039	20.6	4,006	79.4	0.0439	0.92 (0.83–1.03)	0.1571	0.86 (0.76–0.97)	0.0118
Laborer	681	21.9	2,427	78.1	–	1.00 (reference)	–	1.00 (reference)	–
Others	996	22.7	3,393	77.3	–	1.05 (0.94–1.17)	0.4235	1.06 (0.95–1.19)	0.2736
Epinephrine Administration	144	38.9	226	61.1	<0.0001	2.38 (1.92–2.94)	<0.0001	2.10 (1.68–2.61)	<0.0001

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P_a-value: the χ² or two-tailed Fisher’s exact test.

^{^†}

P_b-value: univariable analysis using the logistic regression model.

^{^‡}

P_c-value: Multivariable analysis using the logistic regression model.

^{^§}

Table 3.

The univariable and multivariable analyses of factors associated with necrotizing fasciitis (N = 12,542)

Variable	Necrotizing Fasciitis		No Necrotizing Fasciitis		P_a-Value^*	Univariable Analysis		Multivariable Analysis
Variable	No.	%	No.	%	P_a-Value^*	Crude Odds Ratio (95% CI)	P_b-Value^†	Adjusted Odds Ratio (95% CI)	P_c-Value^‡
All Cases	217	1.7	12,325	98.3	–	–	–	–	–
Males	126	1.4	8,665	98.6	0.0005	0.58 (0.45–0.77)	0.0001	0.58 (0.44–0.78)	0.0003
Age
<18 Years	11	2.4	448	97.6	0.0100	1.00 (reference)	–	1.00 (reference)	–
18–64 Years	135	1.5	8,823	98.5	–	0.62 (0.33–1.16)	0.1361	0.55 (0.29–1.08)	0.0820
≥65 Years	71	2.3	3,054	97.7	–	0.95 (0.50–1.80)	0.8677	0.87 (0.42–1.78)	0.7020
Charlson Comorbidity Index
0	49	1.5	3,147	98.5	0.1516	1.00 (reference)	–	1.00 (reference)	–
1	36	1.4	2,529	98.6	–	0.91 (0.59–1.41)	0.6857	0.97 (0.62–1.52)	0.8825
2	34	1.7	1,975	98.3	–	1.11 (0.71–1.72)	0.6555	1.11 (0.70–1.78)	0.6541
≥3	98	2.1	4,674	97.9	–	1.35 (0.95–1.90)	0.0916	1.25 (0.84–1.85)	0.2675
Types of Antivenom^§
FH	56	0.6	9,138	99.4	<0.0001	1.00 (reference)	–	1.00 (reference)	–
FN	104	4.8	2,046	95.2	–	8.29 (5.97–11.52)	<0.0001	7.80 (5.55–10.96)	<0.0001
FH + FN	42	4.3	925	95.7	–	7.41 (4.94–11.12)	<0.0001	5.99 (3.94–9.12)	<0.0001
Others	15	6.5	216	93.5	–	11.33 (6.31–20.35)	<0.0001	8.67 (4.64–16.19)	<0.0001
Season
Spring	36	1.2	2,879	98.8	<0.0001	1.00 (reference)	–	1.00 (reference)	–
Summer	110	2.4	4,389	97.6	–	2.00 (1.37–2.93)	0.0003	1.52 (1.02–2.25)	0.0397
Fall	56	1.4	3,883	98.6	–	1.15 (0.76–1.76)	0.5070	1.16 (0.75–1.80)	0.4951
Winter	15	1.3	1,174	98.7	–	1.02 (0.56–1.87)	0.9444	1.19 (0.63–2.23)	0.5902
Epinephrine Administration	59	15.9	311	84.1	<0.0001	14.43 (10.48–19.86)	<0.0001	10.69 (7.59–15.06)	<0.0001

Open in a new tab

P_a-value: the χ² or two-tailed Fisher’s exact test.

^{^†}

P_b-value: univariable analysis using the logistic regression model.

^{^‡}

P_c-value: multivariable analysis using the logistic regression model.

^{^§}

Of all the patients, 81.8% (10,263) received systemic antibiotics regardless of a wound infection diagnosis.⁸ Of these patients, 82.5% (7,585) of FH recipients and 75.6% (1,625) of FN recipients received antibiotics. Of all 10,263 patients who received systemic antibiotics, 91.0% (9,339) received cephalosporins or penicillins, and 21.0% (2,155) received combinations with aminoglycosides.⁸ Of the 217 patients in total with necrotizing fasciitis, 74.7% (162) underwent excision or debridement; 56.7% (123) underwent transplantation, reconstruction, or engraftment; and 9.2% (20) underwent amputation.

Neurological complications.

Of the whole patient population, 1.4% (180) experienced neurological complications, and 0.7% (83) required endotracheal intubation.⁸ Neurological complications included stroke in 28.3% (51); acute respiratory failure in 26.1% (47); seizures in 25.6% (46); and peripheral neuropathy in 6.1% (11). Of FH recipients specifically, 1.0% (95) experienced neurological complications, and 0.2% (18) required endotracheal intubation. These rates were higher among FN recipients: 3.2% (68) experienced neurological complications, and 2.1% (46) required endotracheal intubation. In comparison with patients who received FH, those who received FN had an adjusted odds ratio of 3.1 (95% CI: 2.2–4.3; P <0.0001) for the occurrence of neurological complications and 9.3 (95% CI: 5.2–16.5; P <0.0001) for requiring endotracheal intubation (Tables 4 and 5).⁸

Table 4.

The univariable and multivariable analyses of factors associated with neurological complications (N = 12,542)

Variable	Neurological Complications		No Neurological Complications		P_a-Value^*	Univariable Analysis		Multivariable Analysis
Variable	No.	%	No.	%	P_a-Value^*	Crude Odds Ratio (95% CI)	P_b-Value^†	Adjusted Odds Ratio (95% CI)	P_c-Value^‡
All Cases	180	1.4	12,362	98.6	–	–	–	–	–
Males	137	1.6	8,654	98.4	0.0746	1.36 (0.97–1.93)	0.0770	1.33 (0.94–1.89)	0.1084
Age
<18 Years	3	0.7	456	99.3	0.1274	1.00 (reference)	–	1.00 (reference)	–
18–64 Years	123	1.4	8,835	98.6	–	2.12 (0.67–6.67)	0.2012	1.14 (0.35–3.68)	0.8238
≥65 Years	54	1.7	3,071	98.3	–	2.67 (0.83–8.58)	0.0987	1.13 (0.34–3.81)	0.8407
Charlson Comorbidity Index
0	18	0.6	3,178	99.4	<0.0001	1.00 (reference)	–	1.00 (reference)	–
1	25	1	2,540	99	–	1.74 (0.95–3.19)	0.0749	1.78 (0.97–3.27)	0.0644
2	31	1.5	1,978	98.5	–	2.77 (1.54–4.96)	0.0006	2.86 (1.58–5.16)	0.0005
≥3	106	2.2	4,666	97.8	–	4.01 (2.43–6.62)	<0.0001	4.04 (2.39–6.8)	<0.0001
Types of Antivenom^§
FH	95	1.0	9,099	99.0	<0.0001	1.00 (reference)	–	1.00 (reference)	–
FN	68	3.2	2,082	96.8	–	3.13 (2.28–4.29)	<0.0001	3.10 (2.23–4.3)	<0.0001
FH + FN	14	1.4	953	98.6	–	1.41 (0.8–2.48)	0.2362	1.34 (0.76–2.36)	0.3178
Others	3	1.3	228	98.7	–	1.26 (0.4–4.01)	0.6951	1.33 (0.41–4.24)	0.6342
Region
Northern	70	1.6	4,256	98.4	0.009	1.00 (reference)	–	1.00 (reference)	–
Central	37	2.0	1,826	98.0	–	1.23 (0.82–1.84)	0.3092	0.94 (0.62–1.43)	0.7651
Southern	45	1.4	3,173	98.6	–	0.86 (0.59–1.26)	0.4414	0.61 (0.41–0.92)	0.0166
Eastern	28	0.9	3,107	99.1	–	0.55 (0.35–0.85)	0.0075	0.48 (0.31–0.75)	0.0013
Occupation
Agricultural Worker	78	1.5	4,967	98.5	0.0369	1.61 (1.05–2.46)	0.0273	1.47 (0.93–2.33)	0.0975
Laborer	30	1.0	3,078	99.0	–	1.00 (reference)	–	1.00 (reference)	–
Others	72	1.6	4,317	98.4	–	1.71 (1.11–2.63)	0.0140	1.74 (1.13–2.69)	0.0123

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P_a-value: the χ² or two-tailed Fisher’s exact test.

^{^†}

P_b-value: univariable analysis using the logistic regression model.

^{^‡}

P_c-value: multivariable analysis using the logistic regression model.

^{^§}

Table 5.

The univariable and multivariable analyses of factors associated with endotracheal intubation (N = 12,542)

Variable	Endotracheal Intubation		No Endotracheal Intubation		P_a-Value^*	Univariable Analysis		Multivariable Analysis
Variable	No.	%	No.	%	P_a-Value^*	Crude Odds Ratio (95% CI)	P_b-Value^†	Adjusted Odds Ratio (95% CI)	P_c-Value^‡
All Cases	83	0.7	12,459	99.3	–	–	–	–	–
Males	67	0.8	8,724	99.2	0.1046	1.79 (1.04–3.10)	0.0364	1.90 (1.08–3.36)	0.0260
Age
<18 Years	3	0.7	456	99.3	0.9103	1.00 (reference)	–	1.00 (reference)	–
18–64 Years	61	0.7	8,897	99.3	–	1.04 (0.33–3.33)	0.9445	0.85 (0.26–2.82)	0.7908
≥65 Years	19	0.6	3,106	99.4	–	0.93 (0.27–3.15)	0.9071	0.85 (0.23–3.12)	0.8099
Charlson Comorbidity Index
0	20	0.6	3,176	99.4	0.6610	1.00 (reference)	–	1.00 (reference)	–
1	13	0.5	2,552	99.5	–	0.81 (0.4–1.63)	0.5537	0.87 (0.42–1.78)	0.6945
2	15	0.7	1,994	99.3	–	1.19 (0.61–2.34)	0.6039	1.34 (0.66–2.7)	0.4143
≥3	35	0.7	4,737	99.3	–	1.17 (0.68–2.04)	0.5698	1.18 (0.64–2.17)	0.5906
Types of Antivenom^§
FH	18	0.2	9,176	99.8	<0.0001	1.00 (reference)	–	1.00 (reference)	–
FN	46	2.1	2,104	97.9	–	11.15 (6.45–19.26)	<0.0001	9.26 (5.21–16.46)	<0.0001
FH + FN	13	1.3	954	98.7	–	6.95 (3.39–14.22)	<0.0001	5.99 (2.86–12.56)	<0.0001
Others	6	2.6	225	97.4	–	13.59 (5.35–34.57)	<0.0001	10.86 (4.11–28.72)	<0.0001
Anaphylaxis	4	23.5	13	76.5	<0.0001	48.48 (15.47–151.92)	<0.0001	100.36 (27.61–364.74)	<0.0001
Necrotizing fasciitis	18	8.3	199	91.7	<0.0001	17.06 (9.94–29.29)	<0.0001	8.83 (4.99–15.62)	<0.0001

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P_a-value: the χ² or two-tailed Fisher’s exact test.

^{^†}

P_b-value: univariable analysis using the logistic regression model.

^{^‡}

P_c-value: multivariable analysis using the logistic regression model.

^{^§}

Psychological complications.

Within the study cohort, psychological complications developed within 180 days of SBE in 5.2% (654 patients). The complications manifested within 30 days of the SBE in 44.6% (292) of these patients and within 90 days in 77.1% (504). Among individuals with psychological complications, 67.7% (443) received diagnoses of anxiety disorders, including three cases of posttraumatic stress disorder, and 26.9% (176) received diagnoses of depressive disorders. We found no relationship between the occurrence of psychological complications and the types of SBE, but these complications were more common among female patients, adult patients, and patients with comorbidities (Table 6).

Table 6.

The univariable and multivariable analyses of factors associated with psychological complications (N = 12,542)

Variable	Psychological Complications		No Psychological Complications		P_a-Value^*	Univariable Analysis		Multivariable Analysis
Variable	No.	%	No.	%	P_a-Value^*	Crude Odds Ratio (95% CI)	P_b-Value^†	Adjusted Odds Ratio (95% CI)	P_c-Value^‡
All Cases	654	5.2	11,888	94.8	–	–	–	–	–
Males	357	4.1	8,434	95.9	<0.0001	0.49 (0.42–0.58)	<0.0001	0.51 (0.43–0.60)	<0.0001
Age
<18 Years	3	0.7	456	99.3	<0.0001	1.00 (reference)	–	1.00 (reference)	–
18–64 Years	441	4.9	8,517	95.1	–	7.87 (2.52–24.59)	0.0004	4.55 (1.44–14.31)	0.0096
≥65 Years	210	6.7	2,915	93.3	–	10.95 (3.49–34.37)	<0.0001	4.08 (1.28–12.97)	0.0171
Charlson Comorbidity Index
0	53	1.7	3,143	98.3	<0.0001	1.00 (reference)	–	1.00 (reference)	–
1	90	3.5	2,475	96.5	–	2.16 (1.53–3.04)	<0.0001	2.07 (1.46–2.92)	<0.0001
2	100	5.0	1,909	95.0	–	3.11 (2.22–4.35)	<0.0001	2.81 (1.99–3.95)	<0.0001
≥3	411	8.6	4,361	91.4	–	5.59 (4.18–7.47)	<0.0001	4.79 (3.55–6.46)	<0.0001
Types of Antivenom^§
FH	476	5.2	8,718	94.8	0.6321	1.00 (reference)	–	–	–
FN	122	5.7	2,028	94.3	–	1.10 (0.90–1.35)	0.3532	–	–
FH + FN	46	4.8	921	95.2	–	0.91 (0.67–1.25)	0.5735	–	–
Others	10	4.3	221	95.7	–	0.83 (0.44–1.57)	0.5655	–	–
Neurological Complications	28	15.6	152	84.4	<0.0001	3.45 (2.29–5.21)	<0.0001	2.73 (1.79–4.16)	<0.0001
Interhospital Transfer	292	7.4	3,676	92.6	<0.0001	1.80 (1.54–2.11)	<0.0001	1.52 (1.29–1.78)	<0.0001

Open in a new tab

P_a-value: the χ² or two-tailed Fisher’s exact test.

^{^†}

P_b-value: univariable analysis using the logistic regression model.

^{^‡}

P_c-value: multivariable analysis using the logistic regression model.

^{^§}

Hospitalization and interhospital transfer.

Of all the patients, 39.1% (4,902) required hospitalization. The length of stay ranged from 1 to 123 days, with a median of 3 days and an average of 5.7 days. Only two patients were hospitalized for more than 90 days, with stays of 91 and 123 days. In addition, 31.6% (3,968) were transferred to different hospitals. Factors associated with a higher likelihood of hospitalization or transfer included being children, receiving two or more doses of antivenom, and experiencing complications (Supplemental Table 1).

Healthcare costs.

The annual national economic burden of SBE averaged US$1,083,624, with a yearly increase of US$37,641 from 2002 to 2014 (P <0.0001; Figure 1). This accounted for 0.00026% of the gross domestic product. The average healthcare cost per incident amounted to US$1,129 (median, US$548). Factors contributing to higher healthcare costs included being an adult; having a CCI score of 2 or higher; receiving FN treatment; occurrence of SBE in the summer or autumn; occurrence of conditions such as anaphylaxis, wound infections, neurological complications, and psychological complications; and the need for hospitalization or interhospital transfer (Table 7).

Table 7.

The univariable and multivariable analyses of factors associated with healthcare costs (N = 12,542)

Variable	No.	%	Healthcare Costs^*	P_a-Value^†	Univariable Analysis		Multivariable Analysis
Variable	No.	%	Healthcare Costs^*	P_a-Value^†	Crude Odds Ratio (95% CI)	P_b-Value^‡	Adjusted Odds Ratio (95% CI)	P_c-Value^§
All Cases	12,542	100.0	524	–	–	–	–	–
Males	8,791	70.1	513	<0.0001	0.93 (0.91–0.96)	<0.0001	0.99 (0.97–1.01)	0.3608
Age
<18 Years	459	3.7	420	<0.0001	1.00 (reference)	–	1.00 (reference)	–
18–64 Years	8,958	71.4	505	–	1.17 (1.09–1.25)	<0.0001	1.14 (1.08–1.2)	<0.0001
≥65 Years	3,125	24.9	584	–	1.29 (1.21–1.39)	<0.0001	1.16 (1.09–1.23)	<0.0001
Charlson Comorbidity Index
0	3,196	25.5	459	<0.0001	1.00 (reference)	–	1.00 (reference)	–
1	2,565	20.5	474	–	1.03 (0.99–1.07)	0.1295	1.02 (0.99–1.05)	0.2009
2	2,009	16	512	–	1.07 (1.03–1.11)	0.0010	1.03 (1–1.07)	0.0413
3	4,772	38	583	–	1.21 (1.17–1.25)	<0.0001	1.18 (1.14–1.21)	<0.0001
Types of Antivenom^‖
FH	9,194	73.3	486	<0.0001	1.00 (reference)	–	1.00 (reference)	–
FN	2,150	17.1	513	–	1.12 (1.08–1.15)	<0.0001	1.1 (1.07–1.13)	<0.0001
FH + FN	967	7.7	833	–	1.74 (1.66–1.82)	<0.0001	1.59 (1.53–1.65)	<0.0001
Others	231	1.8	881	–	1.66 (1.52–1.82)	<0.0001	1.47 (1.36–1.59)	<0.0001
Year
2002	1,072	8.5	463	<0.0001	1.00 (reference)	–	1.00 (reference)	–
2003	1,019	8.1	390	–	0.77 (0.72–0.81)	<0.0001	0.76 (0.72–0.8)	<0.0001
2004	871	6.9	428	–	0.83 (0.78–0.88)	<0.0001	0.82 (0.77–0.86)	<0.0001
2005	908	7.2	434	–	0.86 (0.81–0.91)	<0.0001	0.84 (0.8–0.89)	<0.0001
2006	997	7.9	455	–	0.88 (0.83–0.94)	<0.0001	0.88 (0.83–0.92)	<0.0001
2007	1,010	8.1	436	–	0.82 (0.77–0.87)	<0.0001	0.83 (0.79–0.87)	<0.0001
2008	1,034	8.2	464	–	0.89 (0.84–0.94)	<0.0001	0.87 (0.83–0.91)	<0.0001
2009	923	7.4	599	–	1.15 (1.08–1.22)	<0.0001	1.09 (1.03–1.14)	0.0014
2010	944	7.5	629	–	1.23 (1.16–1.30)	<0.0001	1.18 (1.12–1.24)	<0.0001
2011	911	7.3	611	–	1.19 (1.12–1.26)	<0.0001	1.17 (1.11–1.23)	<0.0001
2012	945	7.5	636	–	1.23 (1.16–1.30)	<0.0001	1.2 (1.14–1.26)	<0.0001
2013	977	7.8	642	–	1.26 (1.19–1.33)	<0.0001	1.24 (1.18–1.3)	<0.0001
2014	931	7.4	843	–	1.63 (1.54–1.73)	<0.0001	1.62 (1.54–1.71)	<0.0001
Season
Spring	2,915	23.2	505	0.0006	1.00 (reference)	–	1.00 (reference)	–
Summer	4,499	35.9	526	–	1.05 (1.01–1.08)	0.0071	1.04 (1.01–1.07)	0.0078
Fall	3,939	31.4	550	–	1.06 (1.02–1.09)	0.0012	1.06 (1.03–1.09)	<0.0001
Winter	1,189	9.5	486	–	0.99 (0.94–1.04)	0.625	1.04 (1.00–1.08)	0.0808
Region
Northern	4,326	34.5	515	<0.0001	1.00 (reference)	–	1.00 (reference)	–
Central	1,863	14.9	701	–	1.36 (1.31–1.41)	<0.0001	1.24 (1.2–1.28)	<.0001
Southern	3,218	25.7	459	–	0.92 (0.89–0.95)	<0.0001	0.96 (0.93–0.98)	0.0017
Eastern	3,135	25.0	512	–	1.01 (0.98–1.04)	0.6137	1.02 (1–1.05)	0.0714
Anti-Allergy Agents Administration^¶	6,237	49.7	605	<0.0001	1.29 (1.26–1.33)	<0.0001	1.11 (1.09–1.13)	<0.0001
Antibiotics Administration	10,263	81.8	563	<0.0001	1.33 (1.29–1.37)	<0.0001	1.14 (1.11–1.17)	<0.0001
Surgery	914	7.3	990	<0.0001	1.88 (1.79–1.97)	<0.0001	1.37 (1.32–1.43)	<0.0001
Neurological Complications	180	1.4	907	<0.0001	1.68 (1.52–1.86)	<0.0001	1.24 (1.13–1.36)	<0.0001
Endotracheal Intubation	83	0.7	1,283	<0.0001	2.27 (1.95–2.64)	<0.0001	1.26 (1.1–1.44)	0.0007
Psychological Complications	654	5.2	639	<0.0001	1.22 (1.16–1.29)	<0.0001	1.1 (1.05–1.15)	<0.0001
Hospitalization	4,902	39.1	711	<0.0001	1.59 (1.55–1.63)	<0.0001	1.33 (1.3–1.36)	<0.0001
Interhospital Transfer	3,968	31.6	697	<0.0001	1.51 (1.47–1.55)	<0.0001	1.33 (1.3–1.36)	<0.0001

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Median healthcare costs in U.S. dollars.

^{^†}

P_a-value: the Mann-Whitney U test;

^{^‡}

P_b-value: univariable analysis using the log-linear linear regression model.

^{^§}

P_c-value: multivariable analysis using the log-linear linear regression model.

^{^‖}

^{^¶}

Anti-allergy agents: epinephrine, corticosteroids, or antihistamines within 21 days.

DISCUSSION

Among the patients in our study, anaphylaxis, necrotizing fasciitis, and neurological complications developed in very few; however, wound infections developed in a large minority and psychological complications in a notable number. Patients envenomed by N. atra or B. multicinctus (i.e., treated with FN) were more likely to have wound infections, necrotizing fasciitis, and neurological complications than were those envenomed by T. s. stejnegeri or P. mucrosquamatus (i.e., treated with FH). In addition, being female, ederly, and having a high CCI score were associated with an increased likelihood of wound infections and psychological complications. Moreover, patients envenomed by N. atra or B. multicinctus, those with complications, and those needing hospitalization or interhospital transfer incurred higher healthcare costs, which increased over time.

The reported rates of early adverse reactions to antivenom within 24 hours of administration have varied significantly, ranging from 3% to 88%.³⁵^–³⁷^,⁴⁰ Anaphylaxis, the most severe early adverse reaction to antivenom,³⁸ is not defined consistently³⁸^,⁴⁰^,⁴¹; it has been reported in 1–87% of patients.³⁵^,⁴²^–⁵⁶ In Taiwan, antivenom-induced anaphylaxis has occurred infrequently (in 0.1%), and no significant differences in rates of anaphylaxis have been observed among various antivenoms used for SBE. This achievement can be attributed to consistent antivenom purification and fragmentation technology.⁵⁷ Nevertheless, in 3% of SBE cases, epinephrine was prescribed, possibly as a prophylactic measure for patients whose antivenom skin tests yielded positive results.¹⁴^,¹⁵^,²⁴^,²⁵ Although prophylactic epinephrine administration could reduce adverse reactions to antivenom by 80%,⁴⁴ it is still unknown whether it might increase the risk of wound infections and necrotizing fasciitis after SBE.⁵⁸

Our results suggest that wound infections and necrotizing fasciitis are common complications after SBE in Taiwan; the incidence, ranging from 1% to 56%, is comparable to those in other countries.⁵⁶^,⁵⁹^–⁶⁹ Patients envenomed by N. atra or B. multicinctus were at higher risk for these complications than were those envenomed by T. s. stejnegeri or P. mucrosquamatus. These findings are consistent with those of previous studies,¹⁴^,¹⁵^,²⁵^,²⁶^,⁷⁰^–⁷² which indicated that surgery to address wound necrosis and infection was more commonly required for Elapidae SBEs than for Viperidae SBEs. Furthermore, the risk for such complications is higher when SBEs occur during seasons of higher temperature and increased snake activity, such as summer or autumn.⁸^,⁷³ This phenomenon may be attributed to seasonal variations in snake venom potency and oropharyngeal bacterial loads in snakes.⁷⁴^,⁷⁵ However, the higher incidence of complications among female patients remains unexplained. Our study also highlights the excessive use of antibiotics in SBE cases; in contrast, the literature suggests that prophylactic antibiotics should be considered only for Elapidae SBEs, such as those resulting from N. atra bites.⁵⁶^,⁶⁶^,⁶⁹^,⁷⁶^–⁸⁴ Cephalosporins and penicillins were the antibiotics most frequently prescribed in our study. Because of concerns regarding antibiotic resistance, treatment approaches may need to be adjusted.¹⁵^,⁵⁹^,⁶⁰^,⁶³^,⁶⁴^,⁶⁸^,⁷⁸^,⁸²^,⁸⁵^–⁹²

We also found that SBEs in Taiwan were associated with neurological complications, including strokes, acute respiratory failure, seizures, and peripheral neuropathy; this finding mirrored patterns observed in other countries.⁴ Among patients envenomed by T. s. stejnegeri or P. mucrosquamatus, these complications occurred at rates comparable with those seen in Viperidae SBEs from other regions, such as Crotalus, Bothrops, and Lachesis species.⁶⁷^,⁹³^–⁹⁵ Among patients envenomed by N. atra or B. multicinctus, however, the incidence of these complications was lower than that of respiratory paralysis reported in other studies in relation to Elapidae SBEs.⁹⁶^–¹⁰³ This lower incidence in Taiwan is attributed to the fact that the number of B. multicinctus SBEs is lower than that of N. atra SBEs.²⁴^,²⁵ According to several studies, SBE by B. multicinctus necessitated ventilator support because of respiratory paralysis,²⁰^–²³^,¹⁰⁴ whereas SBE by N. atra did not lead to respiratory paralysis in humans.²⁵^,²⁶ A significant proportion of patients had strokes and seizures in our study, in contrast to previous hospital-based studies.¹⁴^,¹⁵^,¹⁰⁵ Although Elapidae SBEs are generally considered to be rarely or not associated with stroke outside of Australia,¹⁰⁶^–¹⁰⁸ our finding is consistent with that of a recent study in which the incidence of stoke among patients envenomed by T. s. stejnegeri, P. mucrosquamatus, N. atra, or B. multicinctus was 8.4% during a follow-up period ranging from 6 months to 3 years.¹⁰⁹

Psychological complications after SBE are influenced by personal trauma experiences and the availability of support resources.⁴ In Taiwan, the NHI system has significantly alleviated the financial burden of medical care in general on patients, which has probably reduced the incidence of psychological complications such as anxiety, posttraumatic stress disorder, and depression among patients with SBE in comparison with those in other countries.¹¹^,⁵⁶^,¹¹⁰^–¹¹⁴ Our findings reaffirmed that female patients are more susceptible to psychological complications¹¹¹ because their levels of perceived stress are higher than those of male patients.¹¹⁵ In contrast, underaged patients in our study were less likely to experience psychological complications, which contradicts previous research findings.¹¹¹^,¹¹⁴ This discrepancy could be attributed to the comprehensive care provided to underaged patients in Taiwan, as indicated by their higher rates of hospitalization and interhospital transfer.

We found that in Taiwan, the average cost of healthcare for SBE was US$1,129, which was higher than that in several countries, including Iran, Myanmar, India, Sri Lanka, Bangladesh, Pakistan, Nigeria, Zimbabwe, and Burkina Faso. It was comparable to costs in South Africa and Mexico but lower than those in the United States, Canada, Spain, and Guyana.⁵^,⁶ Healthcare costs associated with SBE in Taiwan have been steadily increasing annually. This increase in healthcare costs has been accompanied by a rise in the utilization of antivenom doses, despite a decrease in the incidence of SBEs.⁸ The increased use of antivenom in patient treatment is probably attributable to physicians’ recognition that the previously recommended total antivenom doses, based on neutralization studies in animals, are better considered as an initial or starting dose and that subsequent doses should be based on the clinical responses of the patient.²⁷^,¹¹⁶ Owing to a comprehensive health insurance system, the increased use of antivenom in patient treatment did not have an impact on antivenom availability in Taiwan. However, with a surge in antivenom prices in Taiwan from US$250 per bottle before 2016 to US$800 after 2019, we anticipate that healthcare costs will continue to increase significantly.

Limitations.

This study had several limitations. First, the source of our data was the NHI Research Database, in which snake antivenom drug codes were used; thus, our study did not include patients who did not seek medical attention, those with mild symptoms not necessitating antivenom treatment, and those envenomed by D. siamensis before 2008.⁸ Second, our analysis, which was based on bivalent antivenom, could not differentiate among specific snake species, such as between T. s. stejnegeri and P. mucrosquamatus or between N. atra and B. multicinctus. Moreover, the absence of a confirmation test for detecting venom in serum may have introduced identification bias. Third, the NHI Research Database lacks detailed medical records. For example, subtle findings, such as ptosis, might not be documented as primary diagnoses; thus, neurological complications may be underestimated. Furthermore, we were unable to determine the reasons for endotracheal intubation (e.g., surgical requirements for N. atra SBE or respiratory failure in B. multicinctus SBE). The frequency of diagnosis of symptom-based conditions, such as serum sickness, remained unclear.¹¹⁷ Moreover, we could not evaluate other direct effects or complications, such as coagulopathy and kidney injuries, which could be better assessed in hospital-based studies.¹⁴^,¹⁵ Fourth, the use of a single diagnostic code for anxiety or depression, which was less stringent than international guidelines, may have resulted in an overestimation of psychological complications. However, employing a more rigorous standard, especially in situations with uncertain follow-up participation, might have underestimated psychological comorbidities. Finally, healthcare costs in this study covered direct expenses such as antivenom, antibiotics, analgesics, surgeries, and hospitalization fees but did not account for indirect costs such as transportation, communication, food, accommodations, caregiving, and productivity losses. Calculating healthcare costs within a 90-day time frame might also not be the most accurate method. Because of the inherent limitations of retrospective studies, our results should be interpreted with caution.

CONCLUSION

In Taiwan, a substantial proportion of SBEs (21.7%) resulted in wound infections, and a significant number of patients with SBEs (81.8%) received systemic antibiotics. Other complications observed included anaphylaxis (0.1%), neurological complications (1.4%), and psychological complications (5.2%). Wound infections and neurological complications were more likely to develop in patients envenomed by N. atra or B. multicinctus than in those envenomed by T. s. stejnegeri or P. mucrosquamatus. Anaphylaxis and psychological complications were not associated significantly with any specific types of SBE, but the latter tended to be more prevalent among female patients, adult patients, and patients with comorbidities. The study also revealed a worrisome trend of increasing annual healthcare costs and greater antivenom utilization linked to SBE. These findings underscore the importance of implementing educational strategies for physicians to appropriately treat SBE and its related complications.

Supplemental Materials

tpmd240030.SD1.pdf^{(141.1KB, pdf)}

DOI: 10.4269/ajtmh.24-0030

Note: Supplemental materials appear at www.ajtmh.org.

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PERMALINK

A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan

Jen-Yu Hsu

Shu-O Chiang

Chen-Chang Yang

Yan-Chiao Mao

ABSTRACT.

INTRODUCTION

MATERIALS AND METHODS

Patient and public involvement.

Study population and data collection.

Definitions of SBE complications.

STATISTICAL ANALYSES

RESULTS

Anaphylaxis.

Table 1.

Table 2.

Table 3.

Neurological complications.

Table 4.

Table 5.

Psychological complications.

Table 6.

Hospitalization and interhospital transfer.

Healthcare costs.

Figure 1.

Table 7.

DISCUSSION

Limitations.

CONCLUSION

Supplemental Materials

REFERENCES

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Cite

Add to Collections

PERMALINK

A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan

Jen-Yu Hsu

Shu-O Chiang

Chen-Chang Yang

Yan-Chiao Mao

ABSTRACT.

INTRODUCTION

MATERIALS AND METHODS

Patient and public involvement.

Study population and data collection.

Definitions of SBE complications.

STATISTICAL ANALYSES

RESULTS

Anaphylaxis.

Table 1.

Table 2.

Table 3.

Neurological complications.

Table 4.

Table 5.

Psychological complications.

Table 6.

Hospitalization and interhospital transfer.

Healthcare costs.

Figure 1.

Table 7.

DISCUSSION

Limitations.

CONCLUSION

Supplemental Materials

REFERENCES

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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