North American Coral Snake Antivenin for the Neutralization of Non-native Elapid Venoms in a Murine Model

Objectives: North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus fulvius], equine origin) is approved for the treatment of coral snake envenomations in the United States. The coral snake is the only elapid that is native to North America, but envenomations from non‐native elapids are occurring more commonly in this country. This study was designed to evaluate the efficacy of CSAV in the neutralization of two exotic elapid envenomations: Naja naja (Indian cobra) and Dendroaspis polylepsis (black mamba). Methods: A randomized, blinded, placebo‐controlled murine model of intraperitoneal venom injection was employed. Venom potency was determined in preliminary dosing studies. Study animals then were divided into five groups: 1) N. naja venom + CSAV, 2) N. naja venom + 0.9% normal saline (NS), 3) D. polylepsis venom + CSAV, 4) D. polylepsis venom + NS, and 5) CSAV + NS. The venom dose was chosen to be twice the estimated LD ₅₀. The amount of CSAV injected was ten times the amount necessary for neutralization of a 2 × LD₅₀ dose of M. f. fulvius venom in a murine model. Statistical analysis included Fisher's exact and log‐rank testing to compare survival rates and times. Results: Preliminary studies estimated the venom LD₅₀ to be 2.58 mg/kg and 0.45 mg/kg, respectively, for the N. naja and D. polylepsis. A significant difference was shown in comparison of survival times between CSAV–venom groups and normal saline–venom groups despite all animals in both treatment and control arms dying. Animals receiving CSAV and N. naja venom survived (mean ± SD) 24.4 ± 3.0 minutes, versus 17.8 ± 1.3 minutes in the control group (p < 0.001), whereas those receiving CSAV and D. polylepsis venom survived 203.8 ± 37.0 minutes versus 130.0 ± 42.6 minutes in the control group (p < 0.001). All animals in the CSAV + NS group survived to the conclusion of the study. Conclusions: When premixed with venom, CSAV increased survival time in a murine model of intraperitoneal N. naja and D. polylepsis venom injection. The clinical implications of this are unclear, given unchanged mortality rates.     

The Safety and Efficacy of Antivenin Latrodectus mactans

Background: The morbidity associated with snakebite envenomation has not been well documented.

Method: Using a standardized questionnaire all patients with snakebite reported to a regional poison center during the year 2001 were followed after hospital discharge by telephone until resolution of symptoms.

Results: One hundred and twenty-eight snakebite cases were reported, of which 16 (12.5%) were lost to follow-up and 31 (24.2%) reported no progression of symptoms beyond puncture and were deemed “dry bites.” Eighty-one (63.3%) patients were followed for the duration of symptoms. Age ranged from 1 to 86 years with a mean of 32 years. There were 64 males (79%). The snakes were identified as copperhead (n=57), unidentified venomous (n=17), timber rattlesnake (n=6), and cottonmouth (n=1). All patients were initially evaluated in a hospital emergency department of which 51 were admitted. Nine patients received antivenin. Of the 37 patients who had a job, 33 lost a mean of 14 days of work (SD±18.1). Mean duration of edema was reported as 11.4 days (S.D±12). Recurrent edema frequently occurred with limb activity. Pain was scored on a scale of 1 to 10, with a mean score of 4.8 (SD±2.7). Mean duration of pain was reported as 7.8 days (SD±6.4). Thirty patients required accommodation for ambulation including crutches (n=11), limp (n=11), and no shoes or loose shoes (n=14). Of the 26 patients bitten on the hand or finger, duration of reduced function persisted for a mean of 14.3 days (SD±10.4) and reduction of hand strength persisted for a mean of 22 days (SD±25.5). Five patients had poorly healing wounds at the bite site which persisted from 14 to 77 days with a mean of 45 days (SD±22.8)

Conclusion: In this study snakebite resulted in significant duration and extent of morbidity in a majority of patients.     

Elevated Compartment Pressures from Copperhead Envenomation Successfully Treated with Antivenin

Background

Copperhead envenomation causes local soft tissue effects; however, associated compartment syndrome is rare. We report a case of a 17-month-old with significantly elevated compartment pressures successfully treated with antivenin and supportive care.

Case Report

A 17-month-old girl sustained a copperhead bite to the foot and presented with circumferential edema, erythema, and ecchymosis of the foot and distal ankle. The patient had palpable pulses and was neurologically intact. Four vials of Crotalidae polyvalent immune Fab was initiated and additional doses were administered in an attempt to achieve local control. Within 10 h of presentation, the patient's edema extended to the groin, although sensation was maintained and pulses were documented by Doppler. Lower-extremity compartment pressures were measured and were most notable for an anterior pressure of 85 mm Hg, despite having received 12 vials of antivenin. Fasciotomy was deferred and the patient received two additional six-vial doses of antivenin to achieve local control. Compartment pressures improved with a 2.2-cm mean decrease in limb diameter within 48 h. Maintenance dosing was initiated and the patient ultimately received a total of 26 vials of antivenin. The patient did not develop significant coagulopathy or thrombocytopenia. Swelling continued to improve with return of limb function.

Conclusion

In this case, early and aggressive treatment with antivenin may have avoided invasive fasciotomy, and its use should be considered in patients with copperhead envenomation and significantly elevated compartment pressures.     

Antivenin remains effective against African Viperidae bites despite a delayed treatment

Background

Viperidae bites represent a public health issue in Africa and are responsible for a hemorrhagic syndrome with fatal outcome in the short term. A research on Medline database does not reveal any data definitively demonstrating the efficiency of antivenom in case of delayed administration. The aim of this study, based on a 12-year survey of viperine syndromes in Republic of Djibouti, was to compare the normalization of the hemostasis disorders with an early administration of antivenin versus a delayed administration.

Methods

A retrospective study was conducted from October 1994 to May 2006 in the intensive care unit of the French military Hospital, in Djibouti. Seventy-three Viperidae-envenomed patients were included. Antivenin efficiency in correcting hemostatic disorders was analyzed in relation to time to treatment (before or after the 24th hour after the bite).

Results

Forty-two patients (58%) presented with bleeding. A consumptive coagulopathy was found in 68 patients (93%). Antivenin was observed to be effective in improving hemostasis, and the time to normalization of biologic parameters was similar, whether the treatment was started before or after the 24th hour after the bite.

Conclusion

Antivenin should ideally be administered as early as possible. However, in Africa, time to treatment generally exceeds 24 hours. The results of the present evidence-based study confirm an empirical concept: a delayed time to treatment should in no way counterindicate the use of antivenin immunotherapy, in the case of African Viperidae bites.     

抗蝮蛇毒血清静脉输液速度对蝮蛇咬伤患者凝血功能影响的研究

目的 探讨抗蝮蛇毒血清的使用以及其输注时间对患者凝血功能的影响。 方法 回顾性收集2013年4月1日－11月30日首诊于急诊科的蝮蛇咬伤患者的临床资料,根据其过敏试验结果将所有患者分为皮试阴性组和皮试阳性组。再根据两组患者输注抗蝮蛇毒血清时间的长短,将阴性组患者分为输液时间≤1.5 h组和＞1.5 h组;阳性组患者分为输液时间≤3 h组和＞3 h组;记录所有患者的性别、年龄、输注时间、以及输注抗蝮蛇毒血清前后患者的凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、血浆凝血酶时间（TT）纤维蛋白原（FIB）、D-二聚体（D-Dimer）等指标的情况。比较输注抗蝮蛇毒血清前后以及不同输注时间对患者的凝血功能相关指标的影响。结果 阴性组和阳性组输注抗蝮蛇毒血清治疗后,患者的PT、APTT、TT、FIB、D-Dimer均较输注前有所改善,差异均具有统计学意义,输液时间≤1.5 h组和≤3 h组分别较输液时间＞1.5 h组和＞3 h组患者的上述凝血功能相关纠正更明显,差异有统计学意义（P＜0.05）。 结论 抗蝮蛇毒血清能够纠正蛇咬伤患者凝血功能,且输注速度越快对凝血功能的改善效果更明显。     

Rattlesnake Venom-induced Thrombocytopenia Response to Antivenin (Crotalidae) Polyvalent: A Case Series

OBJECTIVE: To test the hypothesis that rattlesnake venom-induced thrombocytopenia would improve following Antivenin (Crotalidae) Polyvalent administration, and that the degree of platelet increase would correlate with the dosage of antivenom. METHODS: The authors conducted a retrospective review of all patients admitted for rattlesnake envenomation at two southern California hospitals between 1980 and 1998. Patients were included if platelet count was less than 150 x 10(9)/L following a rattlesnake bite. Patients were excluded if they received platelet transfusion. The relationship between Antivenin (Crotalidae) Polyvalent administration and venom-induced thrombocytopenia was evaluated by linear regression and paired t-test. RESULTS: The authors identified 103 cases of rattlesnake envenomation. Seventeen cases met inclusion criteria for thrombocytopenia. Two patients were excluded because they received platelet transfusions. One additional patient was excluded from paired t-test only because no antivenom was given. Thrombocytopenia usually improved between presentation and discharge (mean difference, 44 x 10(9)/L), although complete resolution was often not achieved. A statistically significant partial improvement in platelet counts immediately after antivenom administration was observed in a subset of patients with severe thrombocytopenia (platelet count <100 x 10(9)/L) (mean difference, 64 x 10(9)/L). Using regression analysis, the authors did not detect a linear relationship between the amount of Antivenin (Crotalidae) Polyvalent administered and the degree of improvement. CONCLUSIONS: Although rattlesnake venom-induced thrombocytopenia usually improves immediately after Antivenin (Crotalidae) Polyvalent administration and by the time of discharge, the degree of improvement is frequently incomplete and of uncertain clinical significance in the absence of life-threatening bleeding. The authors found no correlation between the degree of improvement and the dosage of Antivenin (Crotalidae) Polyvalent.     

经椎板切开成形术切除椎管内肿瘤

【目的】探讨经椎板切开成形术切除椎管内肿瘤的临床经验。【方法】2010年6月至2013年6月采用后路椎板切开椎管内肿瘤切除后椎板复位成形术治疗16例椎管内肿瘤患者,16例均平均随访12个月,回顾性对比研究手术前后患者神经功能的变化情况。【结果】16例患者13例肿瘤全切,3例次全切除,术后神经根性疼痛均在1周内好转,肢体、躯干运动感觉障碍在3个月内逐渐改善。3例括约肌功能障碍患者中2例在半年内明显改善,1例改善不明显。所有患者均获得门诊随访,随访时间平均12个月。经M RI检查均未见肿瘤复发。2例患者因术中脊髓神经根牵拉术后出现单侧下肢无力,随访半年后1例恢复良好,1例无明显改善,未出现其他并发症。【结论】后路椎板成形治疗椎管内肿瘤安全可靠,疗效满意。     

Rivaroxaban for the Treatment of Pulmonary Embolism

With the advent of new oral anticoagulants (NOACs) for the treatment of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE), a new era of oral anticoagulation for patients with venous thromboembolism (VTE) has begun. Rivaroxaban is the first NOAC to receive regulatory approval for the acute and continued treatment of DVT and PE, and for the secondary prevention of VTE. Here, the clinical trials of rivaroxaban in patients with VTE are reviewed, and the clinical use of rivaroxaban for patients with PE is discussed. Even though rivaroxaban will facilitate the therapeutic management of PE, its use in specific clinical situations needs further study.