謝政昇 李俊達 鄭立福 王健興 吳孟熹 花蓮慈濟醫院外科部整形外科 Date: 2017/03/03 A five-year experience of the poisonous snakebites in the eastern Taiwan 謝政昇 李俊達 鄭立福 王健興 吳孟熹 花蓮慈濟醫院外科部整形外科 Date: 2017/03/03

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Purpose of the study

To identify the demographic data, treatment, and result of the poisonous snakebites in the Eastern Taiwan.

Study method

Data collection: 2010/8/1~2015/6/30 ICD-9 code: 989.5, E905, and E906 Unknown snake bite with antivenom therapy at ER were included. Total 48 patients All of the data were reviewed from the chart

Result

Total patients number: 48 Male: 35 (72.9%), female: 13 (27.1%) Mean age 53.33±14.45 龜殼花: 11 (23%), 青竹絲: 9 (19%), 百步蛇: 3 (6%), 眼鏡蛇: 17 (35%), 鎖鏈蛇: 1 (2%), 雨傘節: 1 (2%), Unknown: 6 (13%) Non OP patients: 29(60.4%), OP patients:19 (39.6%)

Table 2 Demographics(N=48) W/O OP W/I OP Total P-value N 29 (60.4%) 19 (39.6%) 48 Age 53.69±11.92 52.79±18.01 53.33±14.46 0.836 LOS 6.76±6.42 29.32±11.80 15.69±14.22 <0.001* Gender - 0.741 Male 22(75.9%) 13(68.4%) 35(72.9%) Female 7(24.1%) 6(31.6%) 13(27.1%) Site 0.452 Hand 17(58.6%) 8(42.1%) 25(52.1%) Foot 11(37.9%) 9(47.4%) 20(41.7%) Forearm 0(0.0%) 1(5.3%) 1(2.1%) Leg 1(3.4%) 2(4.2%) Extension 23(79.3%) 11(57.9%) 34(70.8%) 0.193 Antivenin 0.001* Neutropic 4(13.8%) 15(31.3%) Hemorrhagic 5(26.3%) 27(56.3%) Combine 2(6.9%) 3(6.3%) NA 2(10.5%)

W/O OP W/I OP Total P-value Antivenin amount(ml) 54.29±27.68 70.00±33.54 60.22±30.64 0.096 Allergy 3(10.3%) 0(0.0%) 3(6.3%) 0.267 就醫間格時間 - 0.164 <1天 25(86.2%) 13(68.4%) 38(79.2%) ≧1天 4(13.8%) 6(31.6%) 10(20.8%) 毒蛇種類 <0.001* 眼鏡蛇/雨傘節 14(73.7%) 18(37.5%) 龜殼花/青竹絲/百步蛇 20(69.0%) 3(15.8%) 23(47.9%) 鎖鏈蛇/NA 5(17.2%) 2(10.5%) 7(14.6%)

Table 1 臨床症狀(N=48) Clinical features No. (%) Systemic syndrome Nausea 2(4%) Vomiting 1(2%) Drooling Ptosis Dysarthria Dizziness Fever 4(8%) Shock 3(6%) Oliguria Dyspnea Skeletal muscle injury 5(10%) Pneumonia Heart failure Local symptoms Swelling 46(96%) Tenderness Erythematous change 45(94%) Bulla formation 15(31%) Ecchymosis 12(25%) Numbness 11(23%)

Cefazolin Gentamycin Oxacillin Augmentin Cephradine 毒蛇種類 N 眼鏡蛇 17 (35%) 2 3 5 龜殼花 11 (23%) 8 1 青竹絲 9 (19%) 6 百步蛇 3 (6%) 雨傘節 1 (2%) 鎖鏈蛇 Unkown 6 (13%) 4 Total 48 20 9 Penicillin Flumarin Tapimycin 1 Ceftazidine Ertapenem 毒蛇種類 N 眼鏡蛇 17 1 龜殼花 11 青竹絲 9 百步蛇 3 雨傘節 鎖鏈蛇 Unkown 6 Total 48

Table 3 手術相關處置(N=19) Item No. (%) 術式 Debride 19(100%) Fasciotomy 14(74%) NPWT 8(42%) 傷口最後處理方式 STSG 9(47%) Primary closure 5(26%) Cross finger flap and FTSG 2(11%) Open amputation Free flap FDMA flap 1(5%) Rotation flap 術中發現 Necrosis 17(89%) Abscess and pus 13(68%) Hematoma accumulation 術後診斷 Necrotizing fascitis 10(53%) Compartment syndrome 4(21%) Wound infection with necrosis

1. Total patients number: 19 Table 5 Bacterial isolates identified from snakebite wounds Organisms N(%) Aerobic gram-negative bacteria 25(49%) Morganella morganii 12 Acinetobacter baumannii 2 Pseudomonas aeruginosa Enterobacter aerogenes 1 Shewanella putrefaciens Serratia marcescens Aeromonas hydrophila E.coli Acinetobacter lwoffii Proteus vulgaris Proteus mirabilis Achromobacter Aerobic gram-positive bacteria 20(39%) Enterococcus species 10 CoNS 7 S.aureus Bacillus species Propionibacterium acnes Anaerobic bacteria 5(10%) Bacteroides fragilis 3 Bacteroides eggerthii Clostridium paraputrificum Eubacterium limosum 1(2%) 1. Total patients number: 19 2. 17 patients (89.5%) had positive culture finding. 3. 眼鏡蛇:14 (74%). 百步蛇:1 (5%), 龜殼花:1 (5%), Unknown:1 (5%) 3. Total pathogen numbers: 51

Table 6 毒蛇種類與細菌配養菌種的相關性 Species N OP(%) Aerobic gram - Morganella morganii Aerobic Gram + Enterococcus species Anaerobic 眼鏡蛇 17 14(82%) 12(70.6%) 11(64.7%) 9(52.9%) 5(29.4%) 龜殼花 11 2(18%) 0(0.0%) 青竹絲 9 0(0%) 百步蛇 3 1(33%) 1(33.3%) 2(66.7%) 雨傘節 1 鎖鏈蛇 Unknown 6 2(33%) 1(16.7%) P-value <0.001* 0.005* 0.199 Data are presented as n or percentage. *p-value<0.05 was considered statistically significant after test

Discussion

Patient number:21 Table 4 Bacterial isolates identified from snakebite wounds Organisms N(%) Aerobic gram-negative bacteria 25(49%) Morganella morganii 12 Acinetobacter baumannii 2 Pseudomonas aeruginosa Enterobacter aerogenes 1 Shewanella putrefaciens Serratia marcescens Aeromonas hydrophila E.coli Acinetobacter lwoffii Proteus vulgaris Proteus mirabilis Achromobacter Aerobic gram-positive bacteria 20(39%) Enterococcus species 10 CoNS 7 S.aureus Bacillus species Propionibacterium acnes Anaerobic bacteria 5(10%) Bacteroides fragilis 3 Bacteroides eggerthii Clostridium paraputrificum Eubacterium limosum 1(2%) 23% 63.9% 13.1%

17 patients had cobra bite, 1 was bitten by T. mucrosquamatus, 1 by T 17 patients had cobra bite, 1 was bitten by T.mucrosquamatus, 1 by T. stejnegeri, and 2 by unknown species. Our data showed the same tendency

Mixed bacterial infections were commonly observed Cobra oral cavities=> M. morganii and Enterococcus Snakebite wound abscesses=> M. morganii was the main GNB in many bacteriological studies Our data also showed the same result

Combined broad spectrum antibiotics were needed to cover aerobes and anaerobes In our cobra bite patients, 2 patient received cefazolin treatment, 3 patients received gentamycin treatment, 5 patients received augmentin treatment

Incomplete pathogen cover Not enough sensitivity Single antibiotic use (68.8%) The combination antibiotics treatment may improve the infection rate from the cobra bite.

Conclusion In this study, the cobra bite was related to the highest operation rate due to the high infection and tissue necrosis possibilities. The most common pathogen from the cobra bite including M.morganii, Enterococcus, and B. fragilis. Combined antibiotics treatment for GNB, GPC, and anaerobic pathogens may have benefit for patient who had a Cobra bite.

Limitation Retrospective study Data collection bias We did not include the non-admission patient No underlying disease collection No antivenom dosage, antibiotics data, and local symptom data after admission.

Reference Bacterial infection in association with snakebite: A 10-year experience in a northern Taiwan medical center Journal of Microbiology, Immunology and Infection (2011) 44, 456e460 Taiwan’s venomous snakebite: epidemiological, evolution and geographic differences Transactions of the Royal Society of Tropical Medicine and Hygiene (2004) 98, 96—101 MANAGEMENT OF POISONOUS SNAKE BITES IN SOUTHERN TAIWAN Kaohsiung J Med Sci 2007;23:511–8 Treatment of Venomous Snakebites in Eastern Taiwan J Plast Surg Asso R.O.C. 2009;18:257∼265 Can surgery in patient with Protobothrops mucrosquamatus envenomation be predicted in emergency department? Hong Kong j.emerg.med. 2016;23:210-219 Can surgical need in patients with Naja atra (Taiwan or Chinese cobra) envenomation be predicted in the emergency department? Hong Kong Med J 2016;22:Epub DOI: 10.12809/hkmj154739 Antivenom Therapy for Crotaline Snakebites: Has the Poison Control Center Provided Effective Guidelines? J Formos Med Assoc 2007;106(12):1057–1062

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W/O OP W/I OP Total P-value 毒蛇種類 <0.001* 龜殼花 9 2 (18%) 11 青竹絲 眼鏡蛇 3 14 (82%) 17 百步蛇 2 1 (33%) 雨傘節 1 鎖鏈蛇 Unknown 4 2(33%) 6 29 19 48 W/O OP W/I OP Total P-value WBC count 0.097 <10000 14 9 23 10000~15000 10 4 15000~20000 5 3 8 >20000 N.seg - 0.452 <75% 18 28 >75% 11 20 N.Band 0.236 <3% 26 40 >3% Platelet 0.687 <150000 2 7 >150000 24 17 41