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Case Report: Management of Pit Viper Envenoming without Antivenom: A Case Series
Abstract
Pit viper envenoming is common in the hilly and the Himalayan regions of Nepal. Antivenom present in Nepal is unlikely to neutralize the venom of these pit vipers, although it has been used often by the healthcare providers in the clinical practice. Here, we report 15 cases of snakebite with a deranged coagulation profile. All patients recovered from envenoming on conservative management and without the administration of antivenom.
... An earlier consultation with a poison center may have prevented the administration of large quantities of antivenom, which can be expensive and have the potential for significant adverse reactions. Envenoming by most South and South-east Asian pit-vipers presents with varying combinations and severity of local effects, hematological abnormalities, myonecrosis and acute kidney injury (Sirur et al., 2022b;Mao et al., 2021;Hifumi et al., 2013;Nishimura et al., 2016;Wongtongkam et al., 2005;Thumtecho et al., 2020;Rathnayaka et al., 2021;Witharana et al., 2021;Bhatt et al., 2020;Cheng et al., 2017;Kim et al., 2019). Envenoming by some species can also trigger thrombotic microangiopathy or mild neuroparalytic effects (Namal Rathnayaka RMMKRanathunga et al., 2018;Igari et al., 2010;Herath et al., 2012). ...
... pdf, 2023). Clinical reports of 4 patients from two studies in lowland Nepal, describe limb swelling (extent varying from a single digit swelling to the entire limb), paresthesia, lymphadenopathy and coagulopathy (Bhatt et al., 2020;Pandey et al., 2021). The median duration of coagulopathy was 4.5 days (Bhatt et al., 2020;Pandey et al., 2021). ...
... Clinical reports of 4 patients from two studies in lowland Nepal, describe limb swelling (extent varying from a single digit swelling to the entire limb), paresthesia, lymphadenopathy and coagulopathy (Bhatt et al., 2020;Pandey et al., 2021). The median duration of coagulopathy was 4.5 days (Bhatt et al., 2020;Pandey et al., 2021). An observational study performed in the Terai region of Nepal, that identified responsible snake species by molecular sequencing of bite-site swabs, confirmed 5 cases of Ovophis monticola bites (Sharma et al., 2016). ...
India is home to a diverse spectrum of medically-significant snakes accounting for the world's largest burden of envenoming, morbidity and mortality. Indian polyspecific antivenom is derived from the venom of four snake species (Daboia russelii, Echis carinatus, Naja naja and Bungarus caeruleus), considered to be responsible for the majority of snakebite morbidity and mortality. The treatment of venomous bites from other less-commonly encountered venomous snake species can be challenging. In this report, we describe the case of a 32-year-old male who presented with features of local cytotoxicity and coagulopathy following a bite from Ovophis monitcola (mountain pit-viper) in Nagaland, northeast India. Local and systemic envenoming, confirmed by bedside and laboratory based clotting assays, failed to respond to polyspecific antivenom and venom-induced consumption coagulopathy persisted for 28 days. Remote consultation with a national Poison Control Centre helped establish the responsible snake species and guide appropriate medical management.
... Of the 132 studies included for full-text review, 11 met the inclusion criteria. Authors from a further 29 studies that reported methodology suggesting synchronous 20WBCT and clotting sample collection were contacted, and a further four studies (from three papers) were included [5,30,31]. Thus, 15 studies were included in the systematic review (Fig 1). ...
... Individual patient data (n = 1,865, 82.2%), were either reported, displayed in figures or provided upon request in nine studies [5,16,[30][31][32]34,36,37]. In these studies, the median INR for patients with a false negative 20WBCT (n = 33) was 1.9 (IQR 1. ...
... Using the individual patient data values described above (n = 1,865), [5,16,[30][31][32]34,36,37] a sub-analysis was performed to assess the ability of the 20WBCT to detect severe coagulopathy, defined as INR >5.0 or fibrinogen <50 mg/dL. The aggregate weighted sensitivity and specificity of the 20WBCT at detecting severe coagulopathy were 0.91 (0.64 to 0.98) and 0.90 (0.74 to 0.96), respectively. ...
Background
The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming.
Methods and findings
Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953).
The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity.
Conclusions
In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom.
... Ovophis monticola (the Mountain Pitviper) is a monotypic species (Malhotra et al, 2011) reported from across the hills of Nepal (Pandey, 2015;Pandey and Thapamagar, 2019) (Figure 1), Bangladesh, northeastern India, northeast, central and western Bhutan, west and southwestern China, northern Myanmar, northern Thailand, southern Laos, northeast and southwest Cambodia , Vietnam, and Malaysia (Grismer et al, 2010;Wallach et al, 2014), where it may cause local and systemic envenomation resulting in throbbing pain, local swelling, blister formation, necrosis, coagulopathy (Wall, 1908;Parajuli et al, 2017), and chronic pain (abnormal neurohumoral and inflammatory syndromes were reported to occur due to a suspected O. monticola envenomation in the hills of eastern Nepal by Bhattarai et al (2008)). However, little is known about circumstances of the confirmed O. monticola bites, evolution of its venom effects, treatment of local and systemic envenomations, and associated burden in its distribution ranges (Wall, 1908;Tillack et al, 2003;Pandey, 2015;Bhatt et al, 2020) although it poses the risk of envenomations throughout the hills of Nepal. Herein, we present circumstances of bite and prehospital care, clinical manifestations and management practices involving several non-evidence-based interventions and using no antivenom, for a confirmed O. monticola envenomation in the central hills of Nepal. ...
... Besides coagulopathy, the O. monticola bite caused distinctive swelling extended proximally to the upper arm. The swelling pattern was similar to the report of edema of a patient envenomed by this species elsewhere (Wall, 1908;Bhatt et al, 2020). Similar swelling patterns were also noticed in other Asian pitviper bites Bhatt et al, 2020). ...
... The swelling pattern was similar to the report of edema of a patient envenomed by this species elsewhere (Wall, 1908;Bhatt et al, 2020). Similar swelling patterns were also noticed in other Asian pitviper bites Bhatt et al, 2020). The pronounced chronic pain experienced by the patient was likely to be complex regional pain syndrome type-1 (Bhattarai et al, 2008) because the edema and chronic pain experienced by her was not associated with the loose-fitting tourniquet that was removed in about 0.6 h post-snakebite in Teku Hospital. ...
We document inadequately diagnosed coagulopathy (potential to be life threatening) due to Ovophis monticola bite. Although its bites are common in the hills of Nepal, associated envenomations have not been documented elaborately. Herein, we present the clinical and treatment details of a proven O. monticola bite and areas where it may pose the risk of envenomations (suggesting huge populations in Asia to be vulnerable to its bites). Its envenomation was managed symptomatically with several non-evidence-based interventions. Since no specific pitviper antivenom is available in Nepal yet, managing coagulopathy associated to O. monticola envenomation is still challenging. This case emphasizes the need of developing the standard protocol for the diagnosis and management of pitviper bites and study of effectiveness of the available pitviper antivenoms until specific pitviper antivenom is available. Further, the demonstrated distribution localities of this species may have implications for snakebite prevention and designing and distribution of the effective antivenoms.
... The 20WBCT was also useful in the detection of new onset coagulopathy post admission, persistent coagulopathy and rebound coagulopathy. Our sensitivity of 87% is higher than findings by Ratnayake et al, Silva et al, and Dsilva et al, who found sensitivities of 82%, 54% and 73% respectively when comparing the 20WBCT to INR > 1.4 [19,24,29,30], but lower than findings by Sharma et al, Bhatt et al and Shenoy, with 89%, 95% and 96% respectively [30][31][32]. A head-to-head comparison of the sensitivities of these studies does not provide an accurate assessment of the performance of the test due to heterogeneity in study setting, snake species, INR cut-offs for defining VICC, study inclusion criteria, sample collection time points and other design and analytical methods. ...
... Of these patients, 7 (50%) had a clinical indication for antivenom, despite the negative 20WBCT (normal), and received antivenom within 6 hours of admission. Other studies comparing 20WBCT to INR report false negative rates ranging from 4% to 46.2% [19,[29][30][31][32]. This suggests that, if used in isolation, the 20WBCT may miss a substantial number of patients who may have mild/moderate envenoming, or who may be early in the envenoming process. ...
Introduction
Envenoming by Echis spp. (carpet or saw-scaled vipers) causes haemorrhage and coagulopathy and represents a significant proportion of snakebites in the savannah regions of West Africa. Early diagnosis of envenoming is crucial in the management of these patients and there is limited evidence on the utility of the 20-minute whole blood clotting test (20WBCT) in diagnosing venom-induced consumptive coagulopathy (VICC) following envenoming by Echis ocellatus.
Methods
A prospective observational cohort study was conducted at the Kaltungo General Hospital in North-eastern Nigeria from September 2019 to September 2021. Standardised 20WBCTs were conducted by trained hospital staff and citrated plasma samples were collected at numerous timepoints. Prothrombin time (PT) and international normalised ratio (INR) were determined using a semi-automated analyser and INR values were calculated using international sensitivity indices (ISI). The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and likelihood ratios of the 20WBCT compared to an INR ≥ 1.4 were calculated, alongside 95% confidence intervals.
Results
We enrolled 121 patients into our study, with a median age of 26 (18.0–35.0) years and a male predominance (75.2%). The 20WBCT was positive (abnormal) in 101 out of 121 patients at timepoint 0h, of which 95 had an INR ≥ 1.4, giving a sensitivity of 87.2% (95%CI 79.4–92.8). Among patients with a negative 20WBCT (normal), six had an INR < 1.4 giving a specificity of 50% (95%CI 21.1–78.9). The positive and negative likelihood ratios were 1.7 (95%CI 1.6–1.9) and 0.3 (95%CI 0.1–0.4) respectively.
Conclusion
The 20WBCT is a simple, cheap, and easily accessible bedside test with a high sensitivity for the detection of patients with venom induced consumptive coagulopathy (VICC) following envenoming by E. ocellatus, although false positives do occur. Repeated 20WBCTs can identify patients with new, persistent, and rebound coagulopathy.
... Envenomation by Viperidae snakes of South Asia results in diverse local effects in envenomed victims. A few examples are local pain, swelling at the bite site, nausea, blistering, and rise of temperature followed by systemic manifestations, including consumption coagulopathy, thrombocytopenia, and platelet dysfunction that may culminate in systemic haemorrhage and constant bleeding from teeth, gum, etc. (Bhatt et al., 2020;Warrell, 2017). Envenoming by green and Salazar's pit viper accounted for most of the envenomation cases presented in Demow Model Hospital; however, no fatality was recorded. ...
... Nevertheless, this study showed similar clinical manifestations in green and Salazar's pit viper bite victims. Snakebite patients in Bayalpata Hospital, Nepal, showed a deranged coagulation profile upon green/mountain pit viper envenomation (Bhatt et al., 2020). Further, a study of 30 pediatric patients from Shimla and Himachal Pradesh also reported frequent hemostatic symptoms (87.5%) involving thrombocytopenia (26.7% of cases), prolonged PT/INR (36.7%), as well as swelling (80.9%) (Sood et al., 2020). ...
Assam, a Northeastern State of India, is inhabited by several venomous snake species causing substantial morbidity and mortality. The data on the epidemiology of snakebites and their management is underreported in this region. Hence, a secondary health-based retrospective study was carried out at Demow Model Hospital, Sivasagar, Assam, to evaluate the clinical and epidemiological profile of snakebite cases reported in this rural hospital and their management. Snakebites occurring between April 2018 to August 2022 were reviewed based on socio-demographic details of the patient, clinical symptoms, and treatment using a standard questionnaire. Out of the 1011 registered snakebite cases, 139 patients (13.7%) counted for venomous bites, among which 92 patients (66.19%) accounted for viper bites (green pit viper and Salazar's pit viper), and 30 patients (21.5%) were bitten by elapid snakes (Indian monocled Cobra, banded krait, and greater/lesser black krait). A maximum number of snakebite cases (80.5%) were reported from the interior rural villages and documented from July to September (51.3%). Elapid snake envenomed patients, except one, were successfully treated with commercial antivenom, neostigmine, and glycopyrrolate. Because commercial polyvalent antivenom against "Big Four" venomous snakes of India showed poor neutralization of pit-vipers envenomation; therefore, pit-viper bite patients were treated with repurposed drugs magnesium sulfate and glycerin compression dressing. Adverse serum reactions were reported only in 3 (11.1%) cases. The preventive measures and facilities adopted at the Demow Model Hospital significantly reduce snakebite death and morbidity; therefore, they can be s practised across various states in India as a prototype.
... Ovophis bites are potentially life-threatening, yet rarely reported. [10][11][12] Six Ovophis spp. are distributed to the South and Southeastern Asia. ...
... 14 An O. monticola bite causes tissue swelling, pain, regional lymphadenopathy, prolonged PT, and peripheral neuropathy, and no antivenom is available or considered effective in reducing its envenoming effects. 11,12,15 Because of the lack of a specific antivenom for Ovophis spp. envenomation, Tan et al. 16 examined the immunoreactivity of four monovalent antivenoms [i.e., antivenom for Calloselasma rhodostoma (produced in Thailand), for D. acutus (produced in China), for Gloydius brevicaudus (produced in China), and for T. albolabris (produced in Thailand)] to the 17 compared the immunoreactivity of monovalent antivenom for T. albolabris (in Thailand) and polyvalent antivenom for hemotoxic snakes (in Thailand; for C. rhodostoma, D. siamensis, and T. albolabris) to the venom of O. monticola. ...
Ovophis makazayazaya bite is an uncommon cause of snakebite that humans may sustain as a result of the continuous overexploitation of forest habitats and excessive development in Taiwan. Although the Taiwanese government has produced four antivenoms against medically important snakebite accidents, O . makazayazaya is not among the snakes for which an antivenom has been produced. A case of O . makazayazaya snakebite on a patient’s right foot, which later swelled into the hip, is reported. In vitro studies have reported that monovalent antivenoms for Gloydius brevicaudus and Trimeresurus albolabris , and polyvalent antivenom for Calloselasma rhodostoma , Daboia siamensis , and T . albolabris show reactivity toward Ovophis venoms. However, these antivenoms are unavailable in Taiwan. Thus, bivalent antivenom for Trimeresurus stejnegeri stejnegeri and Protobothrops mucrosquamatus was used, assuming similar immunoreactivity and a possible para-specific effect of green pit viper antivenom against this Ovophis venom. A favorable outcome was observed, without significant extension in prothrombin time and activated partial thromboplastin time. In addition, no systemic bleeding occurred. Nonetheless, further venom and antivenom evaluations should ascertain the efficacy of this para-specific antivenoms against this crotaline snakebite.
... The lack of paraspecificity of Indian antivenom against Protobothrops envenoming is expected given the fact that the two viperid venoms included in the Indian "Big Four" polyspecific antivenoms are from snakes in sub-family Viperinae, related only distantly to the crotaline members of the genus Protobothrops. Till antivenoms with proven specific/paraspecific activity against Protobothrops venoms are available in India, Protobothrops envenoming should be managed using a conservative approach, without IPAV, as outlined in our report and other literature on the management of pit-viper envenoming in South Asia (Kakati et al., 2023;Ralph et al., 2023;Pandey et al., 2021;Bhatt et al., 2020;Rathnayaka et al., 2021;Namal Rathnayaka et al., 2020). This would avoid unnecessarily exposing patients to the significant adverse reactions associated with IPAV products, the frequency of which can be as high as 43% in some parts of South Asia (de Silva et al., 2016). ...
... monticola) envenoming in Kathmandu [30], a White-Lipped Green Pit Viper (T. albolabris) envenoming in Gorkha [31], pitviper (species not mentioned) envenomings in Achham [51]]. Further, envenomings due to Greater Black Krait (B. ...
Background
Snakebite envenoming is a well-known medical emergency in the Terai of Nepal in particular. However, there is an epidemiological knowledge gap. The news media data available online provide substantial information on envenomings. Assessing this information can be a pristine approach for understanding snakebite epidemiology and conducting knowledge-based interventions. We firstly analyzed news media-reported quantitative information on conditions under which bites occur, treatment-seeking behavior of victims, and outcomes of snakebite envenomings in Nepal.
Methodology/Principal findings
We analyzed 308 Nepalese snakebite envenomed cases reported in 199 news media articles published between 2010 and 2022 using descriptive statistics, Wilcoxon, and Chi-square tests to know why and how victims were bitten, their treatment-seeking behavior, and the outcomes. These envenomated cases known with substantial information represented 48 districts (mostly located in the Terai region) of Nepal. These envenomings mostly occurred in residential areas affecting children. Generally, envenomings among males and females were not significantly different. But, in residential areas, females were more envenomed than males. Further, victims’ extremities were often exposed to venomous snakebites while their active status and these episodes often occurred at night while victims were passive during snakebites indoors and immediate surroundings of houses. Snakebite deaths were less among referred than non-referred cases, males than females, and while active than passive conditions of victims.
Conclusion/Significance
The most of reported envenomed patients were children, and most envenomings were due to cobra bites. Consultation with traditional healers complicated snakebite management. In most cases, deaths that occur without medical interventions are a severe snakebite consequence in Nepal. Further, several deaths in urban areas and mountains and higher hills of Nepal suggest immediate need of snakebite management interventions in the most affected districts. Therefore, there is an urgent need to immediately admit Nepalese snakebite victims to nearby snakebite treatment centers without adopting non-recommended prehospital interventions. The strategies for preventing snakebite and controlling venom effects should also include hilly and mountain districts where snakebite-associated deaths are reported.
... Navin Bhatt et al., [9] (2020) published a case series on American Journal of Tropical Medicine and Hygiene, involving 15 cases of viper bite who were treated conservatively without ASV. All the 15 cases had coagulopathy with deranged coagulation parameters (prolonged WBCT), and all of them were discharged within 3-8 days of snake bite after resolution of coagulopathy. ...
A BSTRACT
Envenoming and deaths resulting from snake bite are a particularly important public health problem in the tropical world, with the highest burden in rural areas of South East Asia and Africa. Snake bite is one of the most severe “Neglected Tropical Diseases” in the world and more importantly in this part of India. We present a case of hemotoxic snake bite where the coagulation parameters remained deranged for a longer time without any active bleeding manifestations, despite treatment with Anti-Snake Venom (ASV) as per the National Treatment Guidelines. Indian Snake Bite Management Protocol emphasizes on the Role of Whole Blood Clotting Time (WBCT) as a bedside, accessible and feasible test for assessment of coagulopathy even in rural settings. Certain scenarios where the patients present late to our hospital with Snake Bite and Venom Induced Consumption Coagulopathy (VICC), the decision regarding ASV prescription in such patients is quite tricky, and needs to be individualized.
Snakebite remains a prior Neglected Tropical Disease in the World, especially in South-East Asia. There were many diversities in the management of snake bites based on the different levels of clinician experience. Anti-snake venom remains the mainstay treatment in venomous snakebites, meanwhile, the distribution of anti-snake venom is very sparse. Snakebite is time-limited and could be a life-threatening event. This case report described a delayed anti-snake venom administration in snakebite grade III following a viper snake bite. Tight observation including clinical manifestation and laboratory tests is the foremost thing to do in managing snakebite, due to its unpredictable clinical manifestation. Anti-snake venom dosage must be decided based on the progress of clinical manifestation and laboratory results.
This case documents envenomation by a Green pit viper (Cryptelytrops sp.), a species found in South and Southeast Asia that causes the majority of venomous snakebites among Southeast Asian pit vipers. The proven life-threatening cases described in published literature, however, are sparse. We report a case of noticeable envenomation due to confirmed Green pit viper, Cryptelytrops sp. bite in Jajarkot. This is the first known reported case of such a bite from Jajarkot in Nepal. This case highlights the urgent need to improve diagnosis, monitoring, and supportive care for snakebite victims in Nepal.
In the Southern Asian countries, snakebite takes a substantial toll in terms of human life, inflicts acute morbidity and long term disability both physical and psychological, and therefore represents a neglected socio-economic problem and severe health issue that requires immediate medical attention. The ‘Big Four’ venomous snakes, viz. Daboia russelii, Naja naja, Bungarus caeruleus and Echis carinatus, are prominent, medically important species and are the most dangerous snakes of this region; therefore, the commercial polyvalent antivenom (PAV) contains antibodies against the venoms of these snakes. However, envenomations by species other than the ‘Big Four’ snakes are grossly neglected, and PAV is only partially effective in neutralizing the venom of these snakes. Many issues confounding effective treatment of snakebite are discussed in this review, and these hurdles preventing successful treatment of snakebite must be addressed. However, in South Asian countries, the pre-hospital treatment and appropriate first aid are equally important to mitigate the problem of snakebite and therefore, these issues are also highlighted here. Further, this review suggests a roadmap and guidelines for the prevention of snakebite and improvement of hospital management of snakebite in these Southern Asian countries.
Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5−11 years) and 10 adults (18−52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855 .
Snake bite, is a significant public health problem and medical emergency in tropical countries including Nepal. Acute renal failure is one of the devastating complications of Russell’s viper envenoming which may cause death of patient in the absence of prompt and adequate management. Treatment with anti-venom and hemodialysis can salvage the patient. Although Russell’s viper is widely distributed in Nepal, AKI due to Russell’s viper envenoming was not reported previously from Nepal.
This case report documents envenomation by an arboreal white-lipped green pit viper (Trimeresurus albolabris), a species found in South and Southeast Asia that causes the majority of venomous snakebites among Southeast Asian pit vipers. Clinical features vary from asymptomatic to serious coagulopathy that may progress into life-threatening or fatal hemorrhage. The proven life-threatening cases described in published literature, however, are sparse. Practically, no specific antivenom targeted to pit viper bites is available in Nepal. We report a case (managed with several non-evidence-based interventions) of noticeable coagulopathic envenomation due to confirmed T albolabris bite in Nepal. This is the first known reported case of such a bite in Nepal. This case highlights the urgent need to improve diagnosis, monitoring, and supportive care for bite victims and to study the effectiveness of Thai pit viper antivenoms for the treatment of T albolabris envenomations.
Venomous snakebite is considered the single most important cause of human injury from venomous animals worldwide. Coagulopathy is one of the commonest important systemic clinical syndromes and can be complicated by serious and life-threatening haemorrhage. Venom-induced consumption coagulopathy (VICC) is the commonest coagulopathy resulting from snakebite and occurs in envenoming by Viperid snakes, certain elapids, including Australian elapids, and a few Colubrid (rear fang) snakes. Procoagulant toxins activate the clotting pathway, causing a broad range of factor deficiencies depending on the particular procoagulant toxin in the snake venom. Diagnosis and monitoring of coagulopathy is problematic, particularly in resource-poor countries where further research is required to develop more reliable, cheap clotting tests. MEDLINE and EMBASE up to September 2013 were searched to identify clinical studies of snake envenoming with VICC. The UniPort database was searched for coagulant snake toxins. Despite preclinical studies demonstrating antivenom binding toxins (efficacy), there was less evidence to support clinical effectiveness of antivenom for VICC. There were no placebo-controlled trials of antivenom for VICC. There were 25 randomised comparative trials of antivenom for VICC, which compared two different antivenoms (ten studies), three different antivenoms (four), two or three different doses or repeat doses of antivenom (five), heparin treatment and antivenom (five), and intravenous immunoglobulin treatment and antivenom (one). There were 13 studies that compared two groups in which there was no randomisation, including studies with historical controls. There have been numerous observational studies of antivenom in VICC but with no comparison group. Most of the controlled trials were small, did not use the same method for assessing coagulopathy, varied the dose of antivenom, and did not provide complete details of the study design (primary outcomes, randomisation, and allocation concealment). Non-randomised trials including comparison groups without antivenom showed that antivenom was effective for some snakes (e.g., Echis), but not others (e.g., Australasian elapids). Antivenom is the major treatment for VICC, but there is currently little high-quality evidence to support effectiveness. Antivenom is not risk free, and adverse reactions can be quite common and potentially severe. Studies of heparin did not demonstrate it improved outcomes in VICC. Fresh frozen plasma appeared to speed the recovery of coagulopathy and should be considered in bleeding patients.
Snake bite is a major public problem in the rural tropics. In southern Nepal, most deaths caused by neurotoxic envenomation occur in the village or during transport to health centers. The effectiveness of victims' transport by motorcycle volunteers to a specialized treatment center, combined with community health education, was assessed in a non-randomized, single-arm, before-after study conducted in four villages (population = 62,127). The case-fatality rate of snake bite decreased from 10.5% in the pre-intervention period to 0.5% during the intervention (relative risk reduction = 0.949, 95% confidence interval = 0.695-0.999). The snake bite incidence decreased from 502 bites/100,000 population to 315 bites/100,000 population in the four villages (relative risk reduction = = 0.373, 95% confidence interval = 0.245-0.48), but it remained constant in other villages. Simple educational messages and promotion of immediate and rapid transport of victims to a treatment center decreased the mortality rate and incidence of snake bite in southeastern Nepal. The impact of similar interventions should be assessed elsewhere.
Venom-induced consumption coagulopathy (VICC) is an important feature of snake envenoming.
To investigate the effect of antivenom and fresh frozen plasma (FFP) on recovery of VICC in Australian elapid snake envenoming.
Prospective cohort study.
Patients with VICC were included from the Australian Snakebite Project (ASP). Time to recovery of VICC (defined as time until INR <2) was investigated using a time to event analysis in WinBUGS. The model considered the effects of age, sex, snake type, time of antivenom after bite, antivenom dose and use of FFP within 4 h.
The study included 167 cases of VICC, median age being 41 [interquartile range (IQR): 28-53) years, and 130 (78%) were males. Antivenom was administered at a median of 3.6 (IQR: 2.2-5.6) h after the bite at a median dose of four vials (IQR: 2-6 vials). Thirteen patients received FFP within 4 h. Recovery of VICC occurred after a median of 14.4 (IQR: 11.5-17.5) h, and only the use of FFP within 4 h influenced the time to recovery. Neither antivenom dose nor time of antivenom administration had an effect on recovery of VICC. In patients administered with FFP, 12% [credible interval (CrI): 6-21%] and 81% (CrI: 61-94%) had recovered at 6 and 12 h, respectively, vs 2.5% (CrI: 1.5-4%) and 28% (CrI: 22-34%) not receiving FFP.
Antivenom did not appear to be effective for the coagulopathy in snake envenoming in Australia. FFP appeared to shorten the time of VICC recovery.
Viper bites cause consumptive coagulopathy resulting in hypofibrinogenaemia. Whole-blood clotting time is a standard test used to assess bleeding risk. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are better standardised assays that are widely available, but their diagnostic accuracy in viper bites remains unknown. Adult patients presumed bitten by green pit vipers (Cryptelytops sp.) were enrolled. Conventional venous clotting time (VCT), 20min whole-blood clotting time (20WBCT), PT with international normalized ratio (INR) and APTT were determined. A fibrinogen level below 1.0g/litre was used as the gold standard. There were 97 patients. The average age was 46.1 years and 49.5% were men. VCT >30min, INR >1.2 and fibrinogen level <1.0g/litre were found in 9.3, 10.3 and 7.2%, respectively. The sensitivities of VCT >30min, 20WBCT (N=55), INR and APTT were 57.0%, 85.7%, 85.7% and 57.1%, respectively. The respective specificities were 94.4%, 95.8%, 95.6% and 72.4%. Three hypofibrinogenaemic patients who did not receive antivenom because of VCT <30min had persistently normal VCT and went home without clinical bleeding. In conclusion, PT with INR can be an alternative test for evaluation of coagulopathy in green pit viper bitten patients with potentially improved inter-laboratory standardisation.
- S K Sharma
- D P Pandey
- K B Shah
- F Tillack
- F Chappuis
- C L Thapa
- E Alirol
- U Kuch
Sharma SK, Pandey DP, Shah KB, Tillack F, Chappuis F, Thapa CL,
Alirol E, Kuch U, 2013. Venomous Snakes of Nepal. ■: ■, 1-76.