Dose Of Antivenom Research Articles

Developing a computational pharmacokinetic model of systemic snakebite envenomation and antivenom treatment

Snakebite envenomation is responsible for over 100,000 deaths and 400,000 cases of disability annually, most of which are preventable through access to safe and effective antivenoms. Snake venom toxins span a wide molecular weight range, influencing their absorption, distribution, and elimination within the body. In recent years, a range of scaffolds have been applied to antivenom development. These scaffolds similarly span a wide molecular weight range and subsequently display diverse pharmacokinetic behaviours. Computational simulations represent a powerful tool to explore the interplay between these varied antivenom scaffolds and venoms, to assess whether a pharmacokinetically optimal antivenom exists. The purpose of this study was to establish a computational model of systemic snakebite envenomation and treatment, for the quantitative assessment and comparison of conventional and next-generation antivenoms. A two-compartment mathematical model of envenomation and treatment was defined and the system was parameterised using existing data from rabbits. Elimination and biodistribution parameters were regressed against molecular weight to predict the dynamics of IgG, F(ab’)2, Fab, scFv, and nanobody antivenoms, spanning a size range of 15–150 kDa. As a case study, intramuscular envenomation by Naja sumatrana (equatorial spitting cobra) and its treatment using Fab, F(ab’)2, and IgG antivenoms was simulated. Variable venom dose tests were applied to visualise effective antivenom dose levels. Comparisons to existing antivenoms and experimental rescue studies highlight the large dose reductions that could result from recombinant antivenom use. This study represents the first comparative in silico model of snakebite envenomation and treatment.

Mathematical Model of In-host Dynamics of Snakebite Envenoming

In this paper, we develop an in-host mathematical model of snakebite envenoming that includes tissue, red blood and platelet cells of humans as specific targets of different kinds of toxins in the snake venom. The model is use to study some harmful effects of cytotoxic and hemotoxic snake venom on their target cells under the influence of snake antivenom. The model has two equilibrium points, namely, trivial and venom free. It has been shown that both the equilibrium points are globally asymptotically stable and numerical simulations illustrate the global asymptotic stability of the venom free equilibrium point. Furthermore, simulations reveal the importance of administering antivenom to avert the possible damage from venom toxins on the target cells. It is also shown through simulation that administering the required dose of antivenom can lead to the elimination of venom toxins within one week. Therefore, we recommend the administration of an adequate dose of antivenom therapy as it helps in deactivating venom toxins faster and consequently enhances the recovery time.

Early Experience with Crotalidae Immune F(ab')2 Antivenom to Treat Arizona Rattlesnake Envenomations.

Crotalidae immune F(ab')2 (Fab2AV) became available in the USA in 2019 for treatment of rattlesnake envenomation. In the clinical trial comparing Fab2AV to crotalidae immune polyvalent fab (FabAV), Fab2AV was associated with less late hemotoxicity. The purpose of this study was to describe outcomes following use of Fab2AV in patients with rattlesnake envenomation in Arizona. This is an observational study of patients admitted to a medical toxicology service at two hospitals in Arizona between January 1, 2019 and December 31, 2020. Patients with rattlesnake envenomation who received Fab2AV were included. Patients who received FabAV, alone or in combination with Fab2AV, were excluded. The main outcomes of interest were antivenom dose, adverse reactions, late hemotoxicity, and hospital readmission or retreatment. Forty-six patients were included. The mean age was 40years, with 15% under 12years of age. All exhibited swelling, 20% thrombocytopenia, and 35% coagulopathy. Median time to treatment was 3h and median total Fab2AV dose was 20 vials. Three patients had an acute reaction to Fab2AV which was non-life-threatening and resolved with antihistamines and/or steroids. In the follow-up period, one case of delayed thrombocytopenia (platelets = 108K/mm3) and one case of recurrent thrombocytopenia (platelets = 111K/mm3) were identified. There was no late coagulopathy. Five patients reported symptoms consistent with mild serum sickness. In this series of patients with rattlesnake envenomation in Arizona who were treated with Fab2AV, there were no cases of clinically significant late hemotoxicity, and no patients required late retreatment with antivenom. Acute and delayed reactions did occur in some patients but were mild and easily treated.

Venomous Snakebites: Treatment Considerations and the Emergency Department Nurse Practitioners'/Providers' Priorities of Care.

In the United States, 7,000-8,000 people are bitten by a venomous snake each year, out of which approximately 5 die. Although common practice is to treat any and all victims of envenomation with repeated doses of antivenom, this approach is not without its risks. The gold standard for treating venomous snakebites with severe symptoms is antivenom. Although a standardized approach to treating envenomation is needed, it cannot be developed without first delineating current practices. This article discusses the ways in which advanced practice emergency nurses should manage bites from a variety of venomous snakes. It is divided into 4 main sections: (1) the types of venomous snakes found in the United States, their habitat, and the effects of their venom; (2) priorities of care in treating venomous snakebites; (3) preparation and administration of antivenom; and (4) other considerations for the advanced practice emergency department nurse.

76 Most Rattlesnake Envenomation Patients Receive Multiple Doses of Antivenom

Antivenom is dosed to clinical effect. Previous reports from a smaller dataset showed that most patients envenomated by rattlesnakes require multiple doses of antivenom, regardless of whether they were treated with Fab or F(ab’)2 antivenom. This study expands previous work to incorporate 2020 data, and describes the dose and timing of both ovine Fab and equine F(ab’)2 antivenom administration for rattlesnake victims.

The Usefulness of Platelet Distribution Width and Platelet Distribution Width to Lymphocyte Ratio in Predicting Severity and Outcomes in Patients with Snakebite.

Tissue damage, inflammatory response, and hematologic abnormalities may occur in snakebite envenomation. This study aimed to evaluate the predictive ability of platelet distribution width (PDW) and platelet distribution width to lymphocyte ratio (PDWLR) in the severity and outcome of envenomation in patients with snakebites in the emergency department (ED). All adult patients admitted to the ED after a snakebite were retrospectively evaluated. Patients were classified according to the severity of envenomation. The relationship between the PDW and PDWLR and envenomation severity and patient outcomes was analyzed. Multivariate logistic regression analysis was performed to determine the predictors of severe envenomation. Results were presented as 95% CIs with odds ratios. Statistical significance was accepted at P<0.05. Envenomation was classified as none/minimal in 42 patients and moderate/severe in 29. PDW and PDWLR were significantly higher in the moderate/severe group (P=0.016 and P<0.001, respectively). Cut-off values of 16.5 for PDW and 6.15 for PDWLR were related to more severe envenomation (area under the curve 0.67, 95% CI 0.55-0.78 and area under the curve 0.85, 95% CI: 0.74-0.92, respectively). Blood product replacement, thrombocytopenia, hematologic abnormality, advanced local findings, compartment syndrome/fasciotomy, antivenom dosing, and moderate/severe envenomation were associated with PDWLR >6.15 (P<0.05). In multivariate analysis, PDWLR (odds ratio 1.19 [95% CI 1-1.4]; P=0.04) was an independent predictor of severe envenomation. Higher PDW and PDWLR were associated with severe envenomation in patients with snakebites in the ED. PDWLR may be used as a predictor of severe envenomation and adverse outcomes.

Reports of Doses Administered and Adverse Reactions to Snake Antivenom Used in Uruguay in 2018.

In Uruguay, around 60 cases of snakebite accidents occur every year that need to be treated with specific antivenom. They are caused by two snakes of Bothrops genus: Bothrops alternatus and Bothrops pubescens. Snakebite accidents are mandatory notification events, allowing the acquisition of an accurate registry and a fluent communication with the health care services. The aim of this study is to analyze and report the doses administered to achieve the neutralization of the venom and the adverse reactions caused by snake antivenoms used in Uruguay in 2018, when a change was made in the type of antivenom available. In this year, Uruguay started to use the BIOL® antivenom (lyophilized) and this use coexists with traditional antivenom liquid forms (Vital Brazil and Malbran). The number of patients treated with heterologous BIOL® antivenom were 28 and the ones treated with heterologous solutions Malbran and Vital Brazil antivenoms were 21. The initial dose of BIOL antivenom was 8 vials instead of 4 vials regularly used with the others antivenoms and it achieved the neutralization of most cases (27/28 cases). Early adverse reactions were detected in 4 patients (3 in children) treated with BIOL antivenom and there were no adverse reactions in those treated with Malbran or Vital Brazil antivenoms. Lyophilized antivenom BIOL is being used widely in Uruguay without major complications.

Challenges in the Management of an Echis coloratus Adult Snakebite Victim at a Tertiary Care Hospital: A Case Report

Patient: Male, 18-year-oldFinal Diagnosis: Snakebite envenomationSymptoms: CoagulopathyMedication:—Clinical Procedure: Anti snake venomSpecialty: General and Internal Medicine • Toxicology • Tropical MedicineObjective:Unusual clinical courseBackground:The World Health Organization has set clear guidelines for the management of snakebite envenomation. However, challenges have been reported in the clinical application of guidelines, such as identification of the biting snake, hypersensitivity reactions to the antivenom, and influence of repeated antivenom administration during hospital stay. This report aims to discuss how these challenges can affect patient management and to highlight improvement opportunities.Case Report:An 18-year-old man presented to the Emergency Department without remarkable signs of envenomation following a snakebite. An initial dose of antivenom was given despite the misidentification of snake species. An allergic reaction developed and was successfully managed. Following admission, the coagulation profile and local tissue reaction worsened. Upon consulting the Drug and Poison Information Center, it was discovered that a subtherapeutic dose of antivenom was administered. The patient was rechallenged after the administration of premedication. Coagulation profile could not be maintained; therefore, 2 extra doses of antivenom were administered, resulting in sustained improvement in local tissue reaction and coagulation profile.Conclusions:First, victims presenting without signs and symptoms of envenomation may benefit from close monitoring for late presentation of envenomation signs. Second, dosing guidelines are suggested to consider Institute of Safe Medication Practices recommendations for order sets to reduce the possibility of medication errors. Third, premedication may be an effective alternative in patients who develop allergic reaction to the locally produced equine antivenom in the setting of absent goat-derived antivenom. Lastly, antivenom administration should be titrated to patient response even if it occurs over several days.

Population pharmacokinetics of Pseudechis porphyriacus (red-bellied black snake) venom in snakebite patients

Objectives Understanding the time course of venom exposure in snakebite patients is important for the optimisation of treatment including antivenom dose and timing. We aimed to investigate the pharmacokinetics of red-bellied black snake (RBBS; Pseudechis porphyriacus) venom in envenomed patients. Methods Timed venom concentration data were obtained from patients with RBBS envenomation recruited to the Australian Snakebite Project (ASP), including demographics and antivenom treatment. Venom concentrations were measured using an enzyme immunoassay. Data were modelled using NONMEM version 7.3. Uncertainty in venom “dose” was accounted for by arbitrarily fixing the average amount to 1 mg and incorporating between-subject variability on relative bioavailability. A scale parameter for venom clearance was implemented to account for the rapid venom clearance following antivenom dosing. A sensitivity analysis was performed to determine the magnitude of venom clearance amplification. Results There were 457 venom concentrations in 114 patients (median age 41, 2–90 y; 80 male). Antivenom was administered to 54 patients a median of 4.2 h post-bite (0.67 to 32 h). A one-compartment model with first-order absorption and elimination provided the best description of the data. The estimated clearance and volume of distribution were 5.21 L/h and 39.9 L, respectively. The calculated elimination half-life of P. porphyriacus venom from the final pharmacokinetic model was 5.35 ± 0.36 h. The variability in the relative dose of injected venom was 140%. Antivenom administration increased venom clearance by 40-fold. Ten patients showed evidence of a double peak in the absorption profile. Conclusion The information on the exposure time of venom in the body following envenomation will help improve treatment and the timing of antivenom.

Quantitation of venom Antigens from Moroccan vipers in serum by using an Enzyme-Linked Immunosorbent Assay (ELISA) toward improving health vigilance systems

In the present study an ELISA assay was developed and validated for detection and determination of the concentration of snakes venom in biological samples. Individual component of each venom (Cerastes cerastes and Macrovipera mauretanica) used as immunogen to raise specific rabbit IgGs in order to set up a sandwich-type ELISA. Lower detection limit, linearity, accuracy, precision, reproducibility, and reference intervals were determined. The method proved to be simple, specific, reproducible, sensitive (detection limit = 0.5 ng/ml) and the calibration plot was based on linear regression analysis (r = 0.980) between 0.9 and 1000 ng/mL of venom concentration, with a lower limit of quantification of 1.58 ng/mL. The intra- and interassay coefficient of variation ranged from 2,02 to 4.62% and 5.29 to 7.40%, respectively. The specificity of the assay was tested using vipers, cobra and scorpion venom. This method detected venom from all viper species tested without significant cross reactivity with other venoms in the concentration range of 0.9–1000 ng/mL. This ELISA described is sufficiently validated for clinical evaluation. The method is adaptable to other venoms. This is potentially useful for clinical diagnosis of snakebite, to monitor antivenom dose, and consequently to improve the national health monitoring systems.

A retrospective evaluation of eastern coral snake envenomation and antivenom administration in cats: 30 cases (2012–2019)

Thirty cats were identified to be have been suspected to have a potential coral snake envenomation after searching medical records from 2012 to 2019 at a university teaching hospital. The records were reviewed and evaluated for signalment, date and time of the snake encounter, elapsed time between encounter and hospital examination, presenting complaint, initial physical examination findings, initial laboratory findings, antivenom dose and duration of administration, adverse reactions to antivenom, additional treatments administered, progression of clinical signs, length of hospitalization, and outcome. Thirteen cats presented with clinical signs consistent with envenomation while 17 cats were treated for possible asymptomatic envenomation, as defined by the owner discovering a live or dead coral snake in their home or on their property. Initial physical examination findings included tachypnea with short shallow breaths and use of accessory muscles; tetraparesis with normal or decreased to absent spinal reflexes; cranial nerve deficits including decreased to absent gag, slow pupillary light reflexes, and absent physiologic nystagmus; and normal or altered mentation. Laboratory findings included hypercapnia, hyperglycemia, hypokalemia, increased aspartate aminotransferase activity, increased alanine aminotransferase activity, echinocytosis, leukocytosis, azotemia, and hyperlactatemia. Twenty-eight cats received antivenom; two cats received two vials while twenty-six cats received one vial. Antivenom reaction was suspected in one cat that developed facial swelling during administration of the drug. Average length of hospitalization was 1 day for cats without clinical signs and 3 days for cats with clinical signs. Twenty-nine cats survived to discharge. Due to the inclusion criteria of the study, cats euthanized on presentation or discharged without receiving antivenom may have been unintentionally excluded from the study.Diagnosis of eastern coral snake envenomation should be suspected in the cat that has acute onset of lower motor neuron neuropathy. Prognosis with treatment is considered good with 97% of cats surviving to discharge. Antivenom reaction occurred in 3.5% of administrations with none being fatal. Monitoring of hypercapnia was critical in making the decision to mechanically ventilate patients. Supportive care that includes antivenom administration, recumbency care, and mechanical ventilation if needed are the mainstays of therapy.

A Bayesian phase 2 model based adaptive design to optimise antivenom dosing: Application to a dose-finding trial for a novel Russell's viper antivenom in Myanmar.

For most antivenoms there is little information from clinical studies to infer the relationship between dose and efficacy or dose and toxicity. Antivenom dose-finding studies usually recruit too few patients (e.g. fewer than 20) relative to clinically significant event rates (e.g. 5%). Model based adaptive dose-finding studies make efficient use of accrued patient data by using information across dosing levels, and converge rapidly to the contextually defined 'optimal dose'. Adequate sample sizes for adaptive dose-finding trials can be determined by simulation. We propose a model based, Bayesian phase 2 type, adaptive clinical trial design for the characterisation of optimal initial antivenom doses in contexts where both efficacy and toxicity are measured as binary endpoints. This design is illustrated in the context of dose-finding for Daboia siamensis (Eastern Russell's viper) envenoming in Myanmar. The design formalises the optimal initial dose of antivenom as the dose closest to that giving a pre-specified desired efficacy, but resulting in less than a pre-specified maximum toxicity. For Daboia siamensis envenoming, efficacy is defined as the restoration of blood coagulability within six hours, and toxicity is defined as anaphylaxis. Comprehensive simulation studies compared the expected behaviour of the model based design to a simpler rule based design (a modified '3+3' design). The model based design can identify an optimal dose after fewer patients relative to the rule based design. Open source code for the simulations is made available in order to determine adequate sample sizes for future adaptive snakebite trials. Antivenom dose-finding trials would benefit from using standard model based adaptive designs. Dose-finding trials where rare events (e.g. 5% occurrence) are of clinical importance necessitate larger sample sizes than current practice. We will apply the model based design to determine a safe and efficacious dose for a novel lyophilised antivenom to treat Daboia siamensis envenoming in Myanmar.

353 Point-of-Care Ultrasound in the Evaluation of Rattlesnake Envenomation

To our knowledge, no prior studies investigated the role of point-of-care ultrasound (POCUS) in the evaluation of rattlesnake envenomation. The objective of this study was to determine the utility of POCUS in the management of rattlesnake envenomation in the emergency department (ED). This was a retrospective review of patients presenting to an academic ED with rattlesnake bite and received a POCUS examination after initial clinical assessment. Proximal progression of symptoms and signs in the affected extremity was monitored clinically and repeat POCUS examinations of the extremity were performed. POCUS findings were collected from ED POCUS database. Medical records were then reviewed for history, physical examination findings, laboratory results, additional diagnostic testing, and disposition. The proportion of patients whose treatment plan was altered by the addition of POCUS findings was determined. A total of 21 patients (mean age 48 years ± 15 (SD); 14 males, 7 females) were included in this study. All patients presented with pain, swelling and tenderness at the site of bite (16-lower extremity, 5-upper extremity). On initial POCUS examination, all patients except one case were noted to have subcutaneous edema at the location of snake bite. Twelve patients were also noted to have cobblestoning on initial POCUS. Myokymia was visualized on initial POCUS in 2 patients. On repeat assessments, POCUS demonstrated subcutaneous edema and cobblestoning more proximally than what was determined and marked by treating emergency physicians in 16 patients. Four patients received additional doses of antivenom based on POCUS findings. The one patient who did not have any sonographic findings on initial POCUS was eventually determined to have dry bite by the toxicologist. Patients with myokymia had a complicated hospital course with thrombocytopenia and deterioration of hemodynamic status. Despite limited numbers, our study suggests that POCUS can be a useful adjunct in the evaluation of patients with rattlesnake bite. Ultrasound appears to be more sensitive than clinical assessment in detecting proximal progression of effects of venom and can potentially guide management. Our ongoing prospective study will further define the role of POCUS in the treatment of rattlesnake envenomation.

Retrospective evaluation of acute kidney injury in dogs with pit viper envenomation (2008-2017): 56 cases.

To describe the clinicopathological characteristics of dogs that develop acute kidney injury (AKI) secondary to pit viper envenomation, and to describe the association between development of AKI and clinical course and outcome. Retrospective study. University teaching hospital. Client-owned dogs treated with at least 1 vial of antivenom following pit viper envenomation and that had at least 2 plasma creatinine concentrations measured during the course of hospitalization. None. Sixty-three dogs met the inclusion criteria. One was excluded due chronic kidney disease, and 6 were excluded due to nonsteroidal anti-inflammatory drug administration. Of the 56 dogs included in the study, 16 developed AKI (29%). Dogs with AKI received a significantly higher dose of antivenom, 8.7 ± 6.8 total vials versus dogs in the non-AKI group that received 4.2 ± 2.6 vials (P=0.006). Dogs in the AKI group were significantly more tachycardic (P=0.028), hypotensive (P=0.002), had a higher shock index (P=0.012), and were more likely to receive transfusions with packed red blood cells (P=0.042) than dogs in the non-AKI group. No significant association was identified between the development of AKI and length of hospitalization. The only factors that were significantly associated with degree of severity of AKI included the receipt of blood transfusion (P=0.006) and number of vials of antivenom administered (P=0.03). The development of AKI was significantly associated with outcome (P<0.001), with 5 of 16 (31%) dogs in the AKI group surviving to discharge, 7 of 16 (44%) dying, and 4 of 16 (25%) being euthanized versus 39 of 40 (98%) surviving to discharge in the non-AKI group and 1 of 40 (2%) dying in hospital. Development of AKI in dogs following pit viper envenomation carries an increased risk of mortality that is associated with severity of shock at presentation and increased doses of antivenom administration.

Delayed antivenom for life-threatening tiger snake bite: Lessons learnt.

An adolescent victim of an urban snakebite developed respiratory failure, rhabdomyolysis and consumption procoagulopathy but recovered with two vials of tiger snake antivenom administered after a delay of 48 hours. The clinical significance of a post-bite collapse was not initially appreciated. Tiger snake (Notechis spp.) venom antigen was measurable in blood before antivenom but not after whereas antivenom was measurable in blood for nine ensuing days. This case adds to growing evidence that further pharmacokinetic research of venom-antivenom interaction is required to establish the correct dose and timing of tiger snake antivenom. Antivenom therapy, even when delayed, facilitates recovery from snake envenomation.

The effect of myocardial injury on the clinical course of snake envenomation in South Korea

Content This study investigated the incidence, progression and clinical course of myocardial injury-related snake envenomation in South Korea. In addition, this study evaluated whether antivenom guidelines are appropriate to control envenomation in patients with myocardial injury. Methods The study included 198 patients who received antivenom after a snakebite, and they were divided into two groups according to evidence of myocardial injury (defined as elevated troponin I or ischemic change on electrocardiogram) at presentation. Data including serial troponin I, echocardiogram/coronary angiogram findings, the clinical course, and treatment were collected and analyzed. Results The incidence of myocardial injury at presentation was 15.2%. The troponin I level was 0.11 (0.07–0.56) ng/ml at presentation and tended to decrease over 24 h. Echocardiograms revealed neither regional wall motion abnormalities nor left ventricular dysfunction in 15 of 17 patients, while two patients showed signs of coronary artery stenosis on echocardiograms and coronary angiograms. However, compared with patients without myocardial injury, patients with myocardial injury had a higher frequency of systemic envenomation complications, including bleeding, respiratory failure, hypotension, acute kidney injury, thrombocytopenia and venom-induced consumption coagulopathy (VICC). The patients with myocardial injury at presentation needed significantly more frequent and larger doses of antivenom than indicated by the initial severity of envenomation. Multivariate analysis showed that myocardial injury was associated with the need for additional antivenom administration after initial administration. Discussion and Conclusion Myocardial injury is not uncommon after snake envenomation in Korea. Although myocardial injury itself seems to be benign, the clinical course of patients with myocardial injury is complicated, and myocardial injury is associated with the need for additional antivenom administration. The optimal use of antivenom to control envenomation in patents with myocardial injury after snake envenomation in South Korea should be established.

Intensive-care management of snakebite victims in rural sub-Saharan Africa: An experience from Uganda.

Antivenom is rarely available for the management of snakebites in rural sub-Saharan Africa(sSA). To report clinical management and outcomes of 174 snakebite victims treated with basic intensive-care interventions in a rural sSA hospital. This cohort study was designed as a retrospective analysis of a database of patients admitted to the intensive care unit (ICU) of St. Mary's Hospital Lacor in Gulu, Uganda (January 2006 - November 2017). No exclusion criteria were applied. Of the 174 patients admitted to the ICU for snakebite envenomation, 60 (36.5%) developed respiratory failure requiring mechanical ventilation (16.7% mortality). Results suggest that neurotoxic envenomation was likely the most common cause of respiratory failure among patients requiring mechanical ventilation. Antivenom (at probably inadequate doses) was administered to 22 of the 174 patients (12.6%). The median (and associated interquartile range) length of ICU stay was 3 (2 - 5) days, with an overall mortality rate of 8%. Of the total number of patients, 67 (38.5%) were younger than 18 years. Results suggest that basic intensive care, including mechanical ventilation, is a feasible management option for snakebite victims presenting with respiratory failure in a rural sSA hospital, resulting in a low mortality rate, even without adequate antivenom being available. International strategies which include preventive measures as well as the strengthening of context-adapted treatment of critically ill patients at different levels of referral pathways, in order to reduce deaths and disability associated with snakebites in sSA are needed. Provision of efficient antivenoms should be integrated in clinical care of snakebite victims in peripheral healthcare facilities. Snakebite management protocols and preventive measures need to consider specific requirements of children. It is estimated that up to 138 000 people die each year following snakebites. Currently, reliable provision of efficient snake-bite antivenom is challenging in many rural health facilities in sub- Saharan Africa (sSA). Our results suggest that basic intensive-care interventions, including mechanical ventilation, is a feasible management option for critically ill snakebite victims in a rural sSA hospital, resulting in a low mortality rate, even without adequate antivenom doses being available.

Clinical manifestations and treatments of Protobothrops mucrosquamatus bite and associated factors for wound necrosis and subsequent debridement and finger or toe amputation surgery

Introduction Protobothrops mucrosquamatus bite induces wound necrosis, coagulopathy, thrombocytopenia, rhabdomyolysis, and acute renal failure. The severity of the hematological derangements and associated factors for wound necrosis and subsequent surgery and the appropriate management of these conditions have not been well characterized. Although severe renal failure requiring hemodialysis has been reported following P. mucrosquamatus bite, the culprit snake may be erroneously classified. Materials and methods A total of 186 patients with P. mucrosquamatus bites were retrospectively evaluated. They were categorized into group 1 (patients receiving debridement or finger/toe amputation) and group 2 (all other patients) to identify the associated factors for surgery. Characteristic data were compared between groups 1 and 2 and between definite and suspected cases. Results No differences were observed between definite and suspected cases in terms of symptomatology and management. Of the 186 patients, 7 (3.8%) were asymptomatic, 179 (96.2%) experienced tissue swelling and pain, and 107 (57.5%) had local ecchymosis. Coagulopathy, thrombocytopenia, and renal impairment were found in 13 (7%), 19 (10.2%), and 7 (3.8%) patients, respectively. None of the patients required transfusion therapy or hemodialysis. Furthermore, no systemic bleeding or death occurred. Antivenom was administered to all 179 envenomed patients at a median of 1.5 h post-bite. The median total dose of the specific antivenom was 5.5 vials. In multivariate logistic regression analysis, finger as the bite site, bullae and blister formation, and wound infection were significantly associated with wound necrosis; whereas finger as the bite site and bullae and blister formation were related to debridement or finger/toe amputation. Discussion and conclusions Protobothrops mucrosquamatus envenomation mainly exerts effects on local tissue. Systemic effects are uncommon and generally nonsevere and transient after the treatment with the specific antivenom. We speculated that severe renal failure requiring hemodialysis is not a typical finding of P. mucrosquamatus envenomation. Patients with finger as the bite site and bullae or blister formation should be carefully examined for wound necrosis, secondary infection, and subsequent surgery. Further evaluations of the efficacy of antivenom against local tissue effects and the effect of selective antibiotics in the management of bite wound infection are urgently required. Although the antivenom manufacturer suggested a skin test prior to use, we believed that it could be omitted because it does not accurately predict the allergic responses.

CORRIGENDUM: Australian snake antivenom dosing: What is scientific and safe?

CORRIGENDUM: Australian snake antivenom dosing: What is scientific and safe?

Envenomation by Trimeresurus stejnegeri stejnegeri: clinical manifestations, treatment and associated factors for wound necrosis.

Background: Trimeresurus stejnegeri stejnegeri bite induces tissue swelling, pain, thrombocytopenia, rhabdomyolysis, and acute renal failure. However, the incidence of coagulopathy, factors associated with wound necrosis, and the appropriate management of this condition have not been well characterized yet.Materials:This study included patients bitten by T. s. stejnegeri that were admitted to the study hospitals from 2001 to 2016. Patient characteristics, laboratory data, and management approaches were compared in victims with and without wound necrosis.Results:A total of 185 patients were evaluated: three patients (1.6%) were asymptomatic; whereas tissue swelling and pain, local ecchymosis, wound necrosis, coagulopathy, thrombocytopenia, rhabdomyolysis, and renal impairment were present in 182, 53, 13, 15, 10, 1, and 3 patients, respectively. One patient died from coagulopathy and hemorrhagic shock. Antivenom was administered to all envenomed patients at a median time of 1.8 h after the bite. The median total dose of antivenom was five vials. Chi-square analysis showed that bitten fingers, using cold packs during first aid, presence of bullae or blisters, lymphangitis or lymphadenitis, local numbness and suspected infection to be significantly associated with wound necrosis. After adjustment using a multivariate logistic regression model, only cold packs as first aid, bulla or blister formation, and wound infection remained significant.Conclusions:The main effects of T. s. stejnegeri envenomation are tissue swelling, pain, and local ecchymosis. We do not recommend the use of cold packs during first aid to reduce wound pain, as this may be a risk factor for wound necrosis. In addition, patients with bulla or blister formation should be carefully examined for subsequent wound necrosis. Antiplatelet use may worsen systemic bleeding. No severe rhabdomyolysis or renal failure was observed in this large case series, we therefore considered that they were not prominent effects of T. s. stejnegeri bite.