Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea.

Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.

Clinico-Epidemiological Profile, Trends, and Health-Related Outcomes of Snakebite Victims: A One-Year Prospective Study from Eastern India.

INTRODUCTION: Snakebite envenomation is a significant life-threatening public health problem in Southeast Asia (SEA). In this region, India reported the largest number of snakebite deaths from 2000 to 2019 (1.2 million), with an average of 58,000 deaths yearly. METHODS: This prospective observational study was carried out among snakebite victims at the emergency department (ED) of a tertiary care public sector hospital in eastern India. RESULTS: A total of 145 cases of venomous snakebite were investigated. More than half (n = 81, 56%) of the snakebite victims were between 17 to 45 years. Most of the snakebite victims were male (68%) and were farmers (53%) by occupation. The majority of snakebites occurred during the daytime (76%) and while outdoors (67%). Most victims sustained a bite on the lower extremity (71%). The peak incidence of snakebites occurred from June to September (69%). Three-quarters of all patients were unaware of the required first aid measures following a snakebite. Among the 145 venomous snakebites, 48 were presumptively identified as the Indian cobra, 32 by the Indian krait, 56 by the Russel's viper, and 9 by saw-scaled viper. The mean duration from the snakebite to the onset of systemic effects in the Indian cobra was 52 ± 14.28 min, 66 ± 18.35 min in the Indian krait, 42 ± 13.47 min in Russel's viper, and 48 ± 16.38 min in saw-scaled viper. Respiratory failure was the commonly observed complication following an elapid envenomation. The mortality rate was 2.1% among the patients treated with antivenom. CONCLUSIONS: Snakebite is considered an occupational hazard in India, commonly affecting the young population in their productive period. The peak incidence was during monsoon season, and the majority had neurotoxic envenomation following an elapid bite (55%) that contributed to the increased mortality and morbidity among young adults. Of the 145 patients, the majority (84%) recovered fully with treatment; 16% of the victims developed morbidity viz cellulitis, respiratory failure, acute renal failure, compartment syndrome, local tissue necrosis, intracerebral hemorrhage, and disseminated intravascular coagulation. Appropriate first aid measures and timely medical intervention can significantly improve the treatment outcome following snakebites.

To bite the hand that feeds you: A case of thrombotic microangiopathy due to Tiger snake bite.

This report details the case of a 51-year-old man with a Tiger snake bite who developed systemic envenomation, coagulopathy and thrombotic microangiopathy (TMA) requiring renal replacement therapy. He received plasma exchange as additional therapy while awaiting confirmation of the cause of the TMA. We discuss clinical decision making in detection of systemic envenomation and management of the rare complication of TMA, as well as current Australian guidelines around antivenom administration. This is the fourth known documented case of TMA from a Tiger snake bite in Australia.

Prolonged venom-induced consumptive coagulopathy following Mangshan pit viper (Protobothrops mangshanensis) envenomation despite Hemato Polyvalent antivenom administration.

This case report summarizes an envenomation by the Mangshan pit viper (Protobothrops mangshanensis), a rare, endangered, venomous snake endemic to Mount Mang of China, and the first reported use of Hemato Polyvalent antivenom (HPAV) for this species. The snakebite occurred in a United States zoo to a 46-year-old male zookeeper. He presented via emergency medical services to a tertiary center after sustaining a single P. mangshanensis bite to the abdomen and was transported with antivenom from the zoo. Within 2 hours of envenomation, he developed oozing of sanguineous fluid and ecchymosis at the puncture site, and about 4 hours post-bite, was treated with HPAV. His coagulation profile fluctuated with the following pertinent peak/nadir laboratory values and corresponding hospital day (HD): undetectable fibrinogen levels, d-dimer 8.89 mg/L and 7.43 mg/L, and INR 2.97 and 1.46 on HD zero and three, respectively. Other peak/nadir values included hemoglobin 9.7 g/dL and creatinine phosphokinase 2410 U/L on HD four and platelets 81 × 109/L on HD seven. The patient received a total of 30 vials of HPAV over 5 days and 1 unit of cryoprecipitate on HD six. Upon discharge on HD eight, laboratory studies were normalizing, except for platelets, and edema stabilized. This case describes an acute, recurrent, and prolonged venom-induced consumptive coagulopathy despite prompt administration and repeated doses of HPAV.

Atrial fibrillation caused by Daboia palestinae snakebite: a case report.

Background: snake envenomation is a serious healthcare issue. Daboia palaestinae is an endemic species to the Middle East that is responsible for the majority of envenomation cases with serious health issue consequences. Case Presentation: we report a case of a 20-year-old Palestinian man who presented to emergency room following a snake bite. He developed atrial fibrillation which is a rare but serious complication of D. palaestinae snakebite. We reviewed the proper approach and management to such cases. Conclusion: cardiac arrhythmias are a rare but serious, often fatal, complication of snake envenomation. Early detection and proper management is key to avoid morbidity and mortality.

Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors.

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A2 (SvPLA2) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA2 catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA2 toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A2, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA2, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA2 effect.

Affected inflammation-related signaling pathways in snake envenomation: A recent insight.

Snake envenomation is well known to cause grievous pathological signs, including haemorrhagic discharge, necrosis, and respiratory distress. However, inflammatory reactions are also common envenoming manifestations that lead to successive damage, such as oedema, ulceration, lymphadenectasis, systemic inflammatory response syndrome (SIRS) and even multiple organ dysfunction syndrome (MODS). Interference with the inflammatory burst is hence important in the clinical treatment of snake envenomation. Here, we summarize the typical snake toxins (or venoms) that cause inflammatory reactions and the underlying signaling pathways. In brief, inflammatory reactions are usually triggered by snake venom phospholipase A2 (svPLA2), snake venom metalloprotease (SVMP), snake venom serine protease (SVSP) and C-type lectin/snaclec (CTL) as well as disintegrin (DIS) via multiple signaling pathways. They are nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), janus kinase/signal transducer and activator of transcription (JAK-STAT) and phosphoinositide 3-Kinase/protein kinase B (PI3K/PKB also called PI3K-AKT) signaling pathways. Activation of these pathways promotes the expression of pro-inflammatory molecules such as cytokines, especially interleukin-1ß (IL-1ß) which causes further inflammatory cascades and manifestations, such as swelling, fever, pain, and severe complications. Remarkably, almost half of introduced snake toxins (or venoms) have anti-inflammatory effects through blocking these pathways and suppressing the expression of pro-inflammatory molecules. Investigation of affected inflammation-related signaling pathways is meaningful to achieve better clinical treatment.

Cortical Blindness and Thrombotic Microangiopathy Following a Hemotoxic Snake Envenomation: An Unusual Presentation.

Snake envenomation leads to significant morbidity and mortality with local, hematological, renal, and neurological complications. Hemotoxic envenomation activates a hemorrhagic cascade, leading to many manifestations ranging from skin bleeds to major organ bleeds and fatal intracranial hemorrhage. Although rare, ischemic manifestations are possible following a hemotoxic envenomation, and they may present as cortical blindness, an unusual ocular symptom. Snake envenomation is also known to cause multifactorial acute kidney injury (AKI), precipitated by hemodynamic disturbances secondary to rhabdomyolysis, hemoglobinuria, direct tubular toxicity, and thrombotic microangiopathy. Thrombotic microangiopathy (TMA) is often overlooked in snake bites, as the hematological manifestations are often conveniently attributed to venom-induced consumptive coagulopathy (VICC). The distinct clinical entity of thrombotic microangiopathy should factor into one's differential diagnosis in patients presenting with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury following a snake bite. We report a patient who developed cortical blindness and thrombotic microangiopathy following snake envenomation, which are uncommon sequelae.

Thromboelastography Use to Guide Resuscitation and Antivenom Administration after Gaboon Viper Bite.

The Gaboon viper (Bitis gabonica) is an exotic snake native to sub-Saharan Africa. Gaboon viper venom is an extremely toxic hemotoxin, causing severe coagulopathy and local tissue necrosis. These are not aggressive snakes and therefore bites involving humans are rare and there is not a substantial amount of literature documenting how to manage these injuries and resultant coagulopathies. We report a 29-year-old male presenting 3 hours after a Gaboon viper envenomation resulting in coagulopathy requiring massive resuscitation and multiple doses of antivenom. The patient received various blood products based on thromboelastography (TEG) and also underwent early continuous renal replacement therapy (CRRT) to assist in correction of severe acidosis and acute renal failure. The combination of TEG to guide resuscitation, administration of antivenom, and early implementation of CRRT allowed our team to correct venom-induced consumptive coagulopathy and ultimately allow the patient to survive following this extremely deadly Gaboon viper envenomation.

Intravenous snake bite: A catastrophic snake envenomation.

The rapid onset of life-threatening clinical manifestations in venomous snake bite could be due to an intravenous bite. This article seeks to review and consider the clinical implications, pathophysiology, and management of this rare route of snake envenomation broadly by venomous snakes which are little described in the available literature.

Résumé L'apparition rapide des manifestations cliniques potentiellement mortelles dans la morsure de serpent venimeux pourrait être due à une morsure intraveineuse. Cet article vise à revoir et à considérer les implications cliniques, la physiopathologie et la gestion de cette rare itinéraire d'envenomations de serpents largement par des serpents venimeux qui sont peu décrits dans la littérature disponible. Mots-clés: Effondrement cardiovasculaire, morsure de serpent intraveineuse, début rapide de la mort, envenimation de serpent.

Hospital admissions due to snake envenomation in the Republic of Cyprus: a 7-year retrospective review.

BACKGROUND: Snake envenomation is a major neglected tropical disease, lacking data in many countries including Cyprus, a Mediterranean island inhabited by the medically important blunt-nosed viper (Macrovipera lebetina). Reviewing the 2013-2019 period, we present first-time epidemiological snakebite data in the Republic of Cyprus. METHODS: We obtained data on snake envenomation-related hospital admissions from the Ministry of Health, and population and rainfall data from the Statistical Service of Cyprus and Department of Meteorology websites. Human-viper conflict information was acquired from interviews with 12 representatives of Cypriot institutions. RESULTS: Between 2013 and 2019, 288 snake envenomation cases were admitted to public hospitals, averaging 41 people annually. The minimum was 29 cases (2017) and the maximum was 58 (2015). Snake envenomation incidence increased from 4.55 per 100,000 population (2013) to 6.84 (2015), but remained low since 2017 (3.49 in 2019). Between 2000 and 2018, the deaths of one man (73 years), and indirectly, one woman (77 years), were related to snake envenomation. While 266 cases (92%) happened between April and October (the blunt-nosed viper activity period), most envenomations occurred in September (cumulative for 2013-2019), with 88 cases (31%). Snakebite incidence peaked in the 60-69 years age group (9.19 per 100,000 population), and was higher in males (6.85) than in females (2.82). Of all admitted patients, 242 (84%) were discharged within 4 days. Mean hospital stay duration was 2.65 days, with one case of 13 days. Most patients were admitted to the general hospitals in Paphos (51%), Limassol (30%) and Nicosia (11%), which provide secondary healthcare, with the last one providing tertiary healthcare. CONCLUSIONS: Snakebite-related deaths are very rare in the Republic of Cyprus. Most envenomation cases happened in late summer (September). Short hospital stays indicate mostly non-severe clinical courses. The hospital admission data suggest that snake envenomation risk is highest in Paphos district. The statistical data hint at males and middle- to older-aged people being at highest risk, whereas from our interview data we assume that outdoor workers are at higher risk than other occupational groups.

Renal and hepatic changes in a case of envenomation by snake bite: Case report and review of literature.

Snake bite is a major health hazard, moreover in tropical countries where the density of snakes, frequent human contact, lack of diagnostic and treatment facilities further add-on to the high morbidity and mortality. No organ escapes the effect of envenomation from Heart to liver and kidney, CNS to local bite site. While the effect of snake venom on kidney has been documented, the literature available on the pathological effects of envenomation in human liver is lacking. We present a case of an elderly male with renal and hepatic manifestations of envenomation.

Effects of cilostazol, a Phosphodiesterase-3 inhibitor, on kidney function and redox imbalance in acute kidney injury caused by Bothrops alternatus venom.

The mechanisms of pathogenesis of acute kidney injury (AKI) in snakebites is multifactorial and involves hemodynamic disturbances, with release of free radical causing cytotoxic effects. The phosphodiesterase-3 (PDE3) inhibitor, Cilostazol, has been reported to provide protection against renal oxidative stress. OBJECTIVE: We evaluated the protective effects of cilostazol against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity. METHODS: Wistar rat kidneys (n = 6, 260-300 g) were isolated and perfused with Krebs-Henseleit solution containing 6 g/100 mL of bovine serum albumin. After 30 min, the kidneys were perfused with BaV to a final concentration of 1 and 3 µg/mL, and subsequently evaluated for perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and percentage of electrolyte tubular sodium and chloride transport (%TNa+, %TCl-). Oxidative stress and renal histological analyses were performed. RESULTS: BaV caused a reduction in all the evaluated renal parameters (PP, RVR, GFR, UF, %TNa+, and %TCl-). Although only the effects on PP and UF were reversed with cilostazol treatment, the decrease in the malondialdehyde levels, without changes in glutathione levels, further reduced the venom-induced renal tissue changes. CONCLUSION: Our data suggest that PDE3 is involved in BaV-induced nephrotoxicity, as cilostazol administration significantly ameliorated these effects.

A Contemporary Exploration of Traditional Indian Snake Envenomation Therapies.

Snakebite being a quick progressing serious situation needs immediate and aggressive therapy. Snake venom antiserum is the only approved and effective treatment available, but for selected snake species only. The requirement of trained staff for administration and serum reactions make the therapy complicated. In tropical countries where snakebite incidence is high and healthcare facilities are limited, mortality and morbidities associated with snake envenomation are proportionately high. Traditional compilations of medical practitioners' personal journals have wealth of plant-based snake venom antidotes. Relatively, very few plants or their extractives have been scientifically investigated for neutralization of snake venom or its components. None of these investigations presents enough evidence to initiate clinical testing of the agents. This review focuses on curating Indian traditional snake envenomation therapies, identifying plants involved and finding relevant evidence across modern literature to neutralize snake venom components. Traditional formulations, their method of preparation and dosing have been discussed along with the investigational approach in modern research and their possible outcomes. A safe and easily administrable small molecule of plant origin that would protect or limit the spread of venom and provide valuable time for the victim to reach the healthcare centre would be a great lifesaver.

A review of 91 canine and feline red-bellied black snake (Pseudechis porphyriacus) envenomation cases and lessons for improved management.

INTRODUCTION: Most cases of red-bellied black snake (RBBS) envenomation in dogs respond favourably to treatment comprising of tiger-brown snake antivenom (TBAV), intravenous fluid therapy, analgesia and, if indicated, mechanical ventilation and/or blood transfusion. However, there remains a subset of patients who develop fatal complications despite intensive treatment and risk factors for these occurring remain unknown. Here we present a retrospective cross-sectional survey of 91 canine and feline RBBS envenomation cases. METHODS: Cases seen between June 2010 and June 2020 were retrieved from the databases of seven practices in South East and coastal Queensland. From the canine case population, logistic regression analysis was performed to assess the impact of potential risk factors at presentation on the likelihood of death. A final multivariable model was developed using a manual backwards elimination approach based on overall likelihood ratio tests and Wald chi-square P-values for each variable. Where model convergence failed due to quasi-complete separation, Firth's penalised maximum likelihood method was implemented. Such separation may occur when an outcome is completely predicted by an explanatory variable in one group. RESULTS: Of the 88 canine cases, 7 died (8.0%), all after prognosis-based euthanasia. Of the three feline cases, one died after unsuccessful resuscitation following cardiopulmonary arrest. Compared to survivors, dogs that died were older, exhibited pigmenturia, received antivenom later and had a higher total plasma protein (TPP), activated clotting time (ACT) and lower packed cell volume (PCV) at presentation.

Hemostatic Analysis of Simulated Gloydius ussuriensis Envenomation Using Canine Blood: A Comparison of Thromboelastography and Classical Coagulation Tests.

Snake envenomation may lead to venom-induced consumptive coagulopathy (VICC), usually diagnosed by classical coagulation tests (CCTs), such as prothrombin time (PT) and activated partial thromboplastin time (aPTT). However, the results of CCTs are frequently normal in the initial stages, which may delay anti-venom treatments. Thromboelastography (TEG) is a point-of-care and real-time diagnostic tool that enables a comprehensive assessment of the coagulation process. This in vitro study aimed to determine concentration-dependent changes in canine blood caused by Gloydius ussuriensis (G. ussuriensis) envenomation using TEG and CCTs. Lyophilized G. ussuriensis venom was reconstructed using mouse intravenous lethal dose 50 (LD50iv) and serially diluted to 25% LD50iv, 50% LD50iv, and 75% LD50iv to reproduce VICC at different concentrations. Normal saline was used for the control. We compared TEG values of the reaction time (R), kinetic time (K), rate of clot formation (α-angle), maximum amplitude (MA), fibrinolysis at 30 min (LY30), and global strength of the clot (G) with those of PT, aPTT, fibrinogen, and platelet counts (PLTs). Most TEG parameters, except R and LY30, demonstrated statistically significant changes compared with the control at all concentrations. CCTs, except PLTs, revealed significant changes at ≥50% LD50iv. Thus, TEG could be a useful diagnostic strategy for early VICC and preventing treatment delay.

Benefits of Sebastiania hispida (Euphorbiaceae) extract and photobiomodulation therapy as potentially adjunctive strategies to be explored against snake envenoming.

The purpose of this study was to assess the topic use of Sebastiania hispida extract and low-level gallium-arsenide laser irradiation (GaAs, 904 nm) to reduce the local myonecrosis and edema of Bothrops moojeni snake venom-injected gastrocnemius. Wistar rats receiving intramuscular venom injection (VBm) were compared with saline control (S) and envenomed rats receiving local exposure to plant extract (VExt) or laser irradiation (VL). The phytochemistry and thin-layer chromatography of S. hispida extract indicated the presence of phenolic compounds like gallic acid and flavonoids including quercetin. Gastrocnemius of VExt and VL groups had a significant reduction of edema and creatine kinase (CK) activities and a greater Myogenin (MyoG) expression compared to VBm group, with the plant extract efficacy better than laser exposure. Reduction of edema and serum CK activities reflects a lessening of muscle damage, whereas the increase of MyoG indicates myoblast differentiation and acceleration of muscle repair. The S. hispida richness in phenolic compounds and flavonoids, such as the light modulatory ability to triggering a multitude of cell signalings likely underlie the positive outcomes. Our findings suggest both treatments as potential auxiliary tools to be explored in clinical trials in combination with anti-venom therapy after Bothropic snakebites.

Potential of herbal cocktail of medicinal plant extracts against 'big four' snake venoms from India.

BACKGROUND: Venomous snake bites cause acute medical emergencies and are fatal. India accounts for large proportion of snake-bite deaths globally. Medically important 'BIG FOUR' snakes of India are Bungarus caeruleus (krait), Naja naja (cobra), Echis carinatus (saw-scaled viper) and Daboia russelii (Russell's viper). Polyherbal formulations have been proved to be effective in treatment of diseases than a single formulation. OBJECTIVE(S): To evaluate aqueous ethanolic extract cocktail of Azadirachata indica, Butea monosperma, Citrus limon, Clerodendrum serratum and Areca catechu for antidote potential against BIG FOUR venoms in ex vivo and in vivo model. MATERIALS AND METHODS: Anti-hemorrhagic and venom neutralization studies were performed in seven-day old chick embryo model for ex vivo studies. In vivo studies were performed using male Swiss albino mice for antivenom potential of herbal cocktail by performing anti-edematic, anti-hemorrhagic, anti-myotoxic activity, and venom neutralization. RESULTS: Herbal cocktail exhibited differential venom inhibition potential against four venoms tested. Hemorrhagic activity was completely neutralized by the herbal cocktail; myotoxic activities of krait and Russell's viper venom were neutralized; while anti-edematic activity was observed for krait and cobra venom. Herbal cocktail completely neutralized venom lethality (3∗LD50) of krait and saw-scaled viper venom. CONCLUSION: Inhibitions of various venom components of all four venoms suggests presence of phytochemicals in herbal cocktail with therapeutic properties. Further studies would help in the development of a formulation as a first-aid towards treatment of snake bite victims.

Serious Adverse Reactions to Anti-snake Venom in Children with Snake Envenomation: An Underappreciated Contributor to Snakebite Mortality?

BACKGROUND: Deaths due to snakebites and serious adverse reactions to anti-snake venom (ASV) are both underreported in India. Serious adverse reactions to ASV are common, contributing significantly to mortality and morbidity. We conducted a study to determine the frequency of occurrence of severe adverse reactions to ASV in children and study the various risk factors and their outcomes. PATIENTS AND METHODS: We carried out a retrospective record review of all children of snake envenomation admitted in our tertiary care teaching hospital, from January 2013 to December 2016. Children aged 0 to 12 years admitted for snake envenomation and who received ASV as part of their treatment were included. Details about their management, including ASV usage and any adverse effects noted, were collected on a standard data collection form. RESULTS: Sixty-eight children were enrolled. Hemotoxic (52.9%) envenomation was more common than neurotoxic (35.2%). Severe adverse reactions were present in 42.6%, hypotension in 38.2%, and bronchospasm in 4.4% of the children. The overall mortality rate was 16.1%, anaphylaxis to ASV contributing to 36.3% of them. Mortality was significantly higher in cases with severe adverse reactions (p = 0.005). ASV reactions were also significantly different with different manufacturers. CONCLUSIONS: There is a high frequency of occurrence of severe adverse reactions to ASV resulting in significant morbidity and mortality. HOW TO CITE THIS ARTICLE: Hooda R, Parameswaran N, Subramanian M. Serious Adverse Reactions to Anti-snake Venom in Children with Snake Envenomation: An Underappreciated Contributor to Snakebite Mortality? Indian J Crit Care Med 2021;25(6):720-723.

Snake bite associated with acute kidney injury.

Acute kidney injury (AKI) is a well-known life-threatening systemic effect of snake envenomation which commonly happens secondary to snake bites from families of Viperidae and Elapidae. Enzymatic toxins in snake venom result in injuries to all kidney cell types including glomerular, tubulo-interstitial and kidney vasculature. Pathogenesis of kidney injury due to snake envenomation includes ischaemia secondary to decreased kidney blood flow caused by systemic bleeding and vascular leakage, proteolytic degradation of the glomerular basement membrane by snake venom metalloproteinases (SVMPs), deposition of microthrombi in the kidney microvasculature (thrombotic microangiopathy), direct cytotoxic action of venom, systemic myotoxicity (rhabdomyolysis) and accumulation of large amounts of myoglobin in kidney tubules. Clinical features of AKI include fatigue, loss of appetite, headache, nausea, vomiting, oliguria and anuria. Monitoring of blood pressure, fluid balance, serum creatinine, blood urea nitrogen and serum electrolytes is useful in managing AKI induced by snake envenomation. Early initiation of anti-snake venom and early diagnosis of AKI are always desirable. Biomarkers which will help in early prediction of AKI are being explored, and current studies suggest that urinary clusterin, urinary neutrophil gelatinase-associated lipocalin, and serum cystatin C may play an important clinical role in the future. Apart from fluid and electrolyte management, kidney support including early and prompt initiation of kidney replacement therapy when indicated forms the bedrock in managing snake bite-associated AKI. Long-term follow-up is important because of chances of progression towards CKD.