European Journal of Cardiovascular Medicine

A serious, perhaps fatal medical emergency that has limited time to treat is snakebite. It is a preventable public health risk that rural residents in tropical and subtropical nations with humid climates and rains frequently encounter. ^[1] A serious health concern is snake envenomation, especially in rural India. Every year in India, between 35,000 and 50,000 people pass away from snake bites. ^[2] In tropical developing nations, snake bites are a widespread, often overlooked, and often fatal occupational and environmental illness, particularly in rural regions. An estimated 2.5 million snake bites occur each year, with 20% of those bites thought to cause serious envenomation. Elapidae are mostly poisonous, which results in characteristics of neurotoxicity. Cobra and Krait, the most frequent neurotoxic envenomations seen in clinical practice, belong to this family. ^[3]

The well-known characteristic of envenoming caused by elapids (Family Elapidae) includes neurotoxicity. Examples of these snakes include death adders (Acanthophis spp.), taipans (Oxyuranus spp.), cobras (Naga spp.), kraits (Bungarus spp.), coral snakes (Micrurus spp.), and tiger snakes (Notechis spp.). Vipers have also been well-described in this context.8 

Neurological symptoms such as Ptosis, Diplopia, Disarthria, Dysphonia, Dyspnea, Dysphagia, and paralysis without local manifestations occur after a common krait bite1. However, there will be both local and neurological symptoms in the event of a cobra bite. Paralysis is brought on by the neurotoxic polypeptide and phospholipases found in snake venom, which obstruct transmission at the peripheral neuromuscular junction. Most elapids, including kraits, coral snakes, mambas, and cobras, exhibit paralytic symptoms when they envenome, but not the African spitting cobra, which is often among Elapids destroy nearby tissue without posing a risk to human health. ^[5] Patients with neuroparalytic snakebite often show symptoms 30 minutes to 6 hours after the bite in the event of a cobra bite and 6 to 24 hours after a krait bite; nevertheless, ptosis in a krait bite has been documented up to 36 hours after hospitalisation. ^[6]

In the Indian subcontinent, the common krait (Bungaruscaereulus) is said to be the most hazardous species of venomous snake. It has been observed that krait bites cause between 35% and 50% of fatalities4. B-bungarotoxin, the primary neurotoxic ingredient of Krait venom, binds strongly to pre-synaptic neuromuscular receptors4. It totally resists anticholinesterase therapy and inhibits these receptors irreversibly. ^[7] Presynaptic (Beta) neurotoxins, which include phospholipase A subunit and 120–140 amino acids, are known as bungarotoxin, crotoxin, and trapoxin. These cause injury to the nerve terminals at neuromuscular junctions after releasing acetylcholine, which stops further neurotransmitter release. The three-finger toxin family includes cobra venom toxins that function post-synoptically. They are divided into three primary categories: non-conventional alpha neurotoxins, short chain, and long chain. Because of their similarity to the effect of d-tubocurarine (dTC), these neurotoxins are referred to be "curare-mimetic." Ach binding to muscle nAChR is competitively inhibited to cause dTC block. It's not apparent what defines reversibility of blockage, despite the fact that it would be vital to the effectiveness of therapeutic therapies. ^[8]

Study Design –A comparative observational study
Study period - June 2019 to September 2020
Inclusion Criteria
All cases of neurotoxic snake bite patients of age 14 and above admitted in SIMS Medical College and hospital with normal 20-minute WBCT and bleeding manifestation.
Patients who have given informed consent.
Exclusion Criteria
Non-venomous snakebite and Venomous snakebites with no neurological manifestations.
Pregnant women and person with any co-existing illness were excluded
Age less than 14 years.
Snakebite case with neurological manifestation but with abnormal 20minute WBCT.
Snakebite cases with known neurological disease.
Methodology
The Institutional Ethical Committee will grant ethical clearance, and patients will provide written, informed consent. Over the course of a year, comparative observational research will be carried out. A minimum of fifty patients, both male and female, who were hospitalised to SCB MCH and had a history of neurotoxic snake bite with neurological manifestations are investigated. The identification of the offending snakes will be done by inspection (in the event that the snake is killed and sent to the hospital) or by relying on the testimony of eyewitnesses. The eyewitness will be shown pictures of the snakes to further substantiate the picture they took. Apart from cases of unidentified snake bites or unidentified bites with poisonous neurotoxic manifestation without a local sign will be regarded as a Krait bite, while manifestation with a local sign will be classified as a Cobra bite.
A comprehensive clinical examination and full clinical history will be taken of the patient who has been bitten by a snake. WBCT will take place in 20 minutes. The National Guidelines will be followed while administering the anti-snake venom injection. A dosage of 0.5 millilitres of Neostigmine will be administered intravenously. The patient will be monitored for ptosis severity and muscle strength over the course of 10, 20, and 30 minutes. For additional research, 5 millilitres of blood will be stored at -200 C. Patients who are ambulatory will have electrophysiological testing done

In our study of neurotoxic snake bites, a total of 50 cases has been studied over a span of 2 years from May 2019 to September 2020. Out of these 50 case 39 cases were confirmed/probable krait bites (78%) and 11 cases were confirmed/probable cobra bites (22%). So it is concluded that majority of cases of neurotoxic snake bites in our place is due to krait bite which frequently enters human dwelling

The above table shows that most of the cases of neurotoxic snake bites (50%) occurred within the 21-40yrs age group. The youngest patient in the study group was 14yrs male and female and the oldest 68 yrs male. The male to female ratio in the study was 2.8:1. Out of the 11 cases of cobra bites majority (72%) has occurred in males. Out of the 39 cases of krait bites 74% has occurred in males. There is hardly no difference between the male and female predominance of neurotoxic snake bite.

A majority of snake bite (54%) has occurred among farmer and labourers. Out of which 33.3% of Krait bite and 36.2% are Cobra bite. A significant portion (22%) of bite has also occurred among housewives among which 20.5% of Krait bite and 27.6% are of cobra bite.

It was observed in the study that 62% of cases occurred between 6PM to 6AM. A majority of cobra bite occurred between 00 AM and 6 AM, also between 12PM to 6PM. A majority of Krait bite (44%) has occurred during early morning time. Time bite of 3 cases of krait is unknown because sometimes krait bite is painless and patient is unaware of snakebite but they presented as neurotoxic snake after some hours.

From the above table it is clear that most of the snake bite occurred in the house and majority of which occurred while sleeping on the floor. Out of these, 71.8% cases were krait bites and only 45.5% was cobra bite. Majority of cobra bite has occurred in the field (54.5%) in comparison to krait bite (43%).

The site of bite was the lower extremities in maximum number of patients (56%). Out of these Krait bite (53.8%) and cobra bite (63.6%) occurred in the lower limbs. Significant number of krait bite (35.9%) in the upper limb. Krait bite can be found all over the body parts including back, head and neck, trunk as most of the bites occurred during sleep hours inside the house but cobra bite is predominantly found in upper and lower extremities as farmers and labourer working in the field.

In most of the cases the symptoms appeared after 1-4 hrs of snake bite with a mean delay of 2.56_+0.09hrs. Maximum delay in onset of symptoms in this study was 6 hrs, which was a case of suspected krait bite. In majority of cobra bite (72.7%) and krait bite (76.9%) the onset of the first symptom occurred within 4hrs

The current study comprised fifty instances of neurotoxic snake bites that were admitted to the Hospital within a two-year period.They had a thorough history taking, a clinical assessment, and a laboratory analysis. Distribution of cases by age and gender
It is clear from the current study that the majority of cases (50%) happened in the age range of 21 to 40 (Table 1). In this study, a 14-year-old man is the youngest victim, and a 58-year-old guy is the oldest. The presentation age is 37.5 years (SD_+13.8) on average. Sawai et al. (1974) reported on the findings of interspace research, which show that 71% of the fatalities fall within this age range. [9] The finding is further supported by research by David G. Laloo (1995) and Banerjee RN (1974) that found that about 80% of the fatalities belonged to the same age group. [10,11] The average age of presentation in the research was 25.2 years. Research by Virmani SK et al. (1996) found that studies were indicated in 56% of the cases. [12]
The majority of bites (52%) and krait bites (54.4%) in this research happened at night when the victims were asleep. In India, over 86% of bites happened between the hours of 6 AM and midnight, according to Sawai et al. (1974). [13] Research conducted at Safdarjung Hospital revealed a similar observation: 81% of bites happened during the day. The report of a vasculotoxic snake bite in their research series might be the reason for this. [14] The bulk of cobra bites (36.4%) and krait bites (54.4%) have happened in the early morning or afternoon. Sixty-six percent of the bites in the current series have happened inside. Of these cases, 71.8% involved bites from kraits, while only 45.5% involved cobra bites. the majority of krait bites have happened mostly in the field (54.5%), with the bulk occurring inside homes (71.8%). This discrepancy results from the behaviours of kraits, who regularly break into homes throughout the night to find prey and attack their victims (Warrel DA, 1996). [15] Cobras, on the other hand, do not invade human homes as frequently. Similar prevalence with nighttime preponderance was also noted by Veeramani SK et al. (1986). In his research, 88% of the events took place at night. [16]
In the majority of patients (56%), the bite location was the lower extremities. Of these, the lower limbs were the site of krait bites (53.8%) and cobra bites (63.6%). A notable proportion of krait bites (35.9%) occurred in the upper limb. Only 10.3% of patients had a krait bite in their head, neck, back, or trunk. According to David G. Laloo et al. (1995), 96% of the bites in their research group happened to the lower limbs. [17] The lower extremities were found to be the most prevalent site of bites (67.8%), with the feet being the most common site (41.1%), according to Sawai et al. [18]
In the lack of venom antigen testing and direct snake observation, the current investigation was unable to conclusively distinguish between cobra and krait bite conditions. 52.4% of instances had the snake recognised, while 48% of patients had no way to identify the snake since most bites happened while the victim was asleep. However, the clinical manifestation of a cobra bite is localised edoema and necrosis because the venom contains cardiotoxin. They showed no signs of local edoema in a bite from a krait. Several workers' investigations have revealed little local edoema following a krait bite. Minton SA (1990) reported comparable results in bites caused by kraits when there is either no local edoema or very little. [19] Warrel DA (1983) reported three bite instances caused by kraits in which There was some redness and mild edoema. [20]
With a mean delay of 2.56% +/- 0.09 hours, the symptoms manifested in the majority of cases 1-4 hours following the snake bite. In one instance of a suspected krait bite, the investigation found that the maximum delay in symptom onset was six hours. The majority of cases in both cobra (72.7%) and krait (76.9%) had the first symptom appear within four hours. According to the study, symptoms appear earlier in cobra bite cases than in bites by kraits (Table no. -7). According to Minton (1990), the neurotoxic symptoms of a cobra bite can occasionally be identified in three minutes and are seldom postponed for longer than six hours, but with a krait bite, the beginning is often delayed by at least one hour.

The bulk of the neurotoxic snake bites that were reported were from Kraits (70.2%), with cobra bites accounting for the remaining 22 percent. The majority of neurotoxic snake bites (2.8:1), which affect mostly farmers and labourers between the ages of 21 and 40 (50%) occur in this age range. Most bites have happened at night when people are sleeping (52%). Clinical signs appear between 1-6 hours, with ptosis being the most prevalent (100%) of the spectrum of clinical manifestations. When compared to other krait bites, the symptoms of a krait bite manifest earlier. Both cobra and krait bites have fang marks. However, blisters and localised swelling with necrosis of the tissue are exclusively seen in cobra bites. First, fourth, and fifth cranial nerves are frequently affected following a neurotoxic snake bite, with the third cranial nerve being the most frequently affected and predominating in krait bite cases. Neostigmine is usually needed for 48–72 hours per patient, and 20.2 vials of ASV are often needed. Patients who have been bitten by cobras require fewer doses of neostigmine medication. In three days, the majority of patients (54%) recovered. In every instance of a neurotoxic snake bite, the coagulopathy measure (PT/INR) was determined to be normal. Both cobra and krait bites have aberrant serum CPK levels, however all cobra bites have abnormal serum CPK levels. On days three through five of hospitalisation, the findings of the EMG and NCV tests for both cobra and krait bites were completely normal. The majority of patients healed in three days or less. Thus, this suggests a snake bite. Without causing any lasting paralysis, neurotoxicity is reversible. In every instance, there was normal conduction of the motor and sensory nerves. The amplitude and configuration of CAMP and SNAP did not exhibit any abnormalities. This proves the venom doesn't affect the peripheral nerve.

1. Government of India, National Snakebite Protocol, New Delhi; Health and Family Welfare Department, 2007
2. Devid A Werrell, World Health Organization Guidelines for The Management of Snake Bite, 2010.
3.Patwari P, Savgle S.A., Mane Abhy A, Doshi S, Kadam D.B., Comparative Study of electrophysiological changes in Snake bites. Neurology India, May 2015, Volume 63, Issue 3.
4.Swarnakar H.S., Bhawarkar P.H., Envenoming by the Common Krait (BungarusCaeruleus) and Asian Cobra (Naga Naga): Clinical Manifestation and Their management in Rural Setting. Wilderness and Environmental Medicine,!5, 257-266(2004)
5.Warwell D.A, Venomous and Poisonous Animals. Mamson’s Tropical Diseases 2014;75:1096-1117
6.Anil A, Singh S, Bhatta A, Sharma N., Agrawal R, Simpson Ian D., Role of Neostigmine and Polyvalent anti-venom in Indian common Krait (BungarusCaeruleus) bite; Journal Infection and Public Heath(2010) 3, 87-88.
7.Lee S.W, Jung I.C, Yoon Y.H, Hong S.H, Han K.S, Choi S.H, Hong Y.S., Anticholinesterase therapy for patient with Opthalmoplegia following snakebite: Reports of two cases: J Korean Med Science 2004;19:631-3
8.Ranawaka U.K, Laloo David G., Silva H.J.De; Neurotoxicity in Snakebite-The Limits of our Knowledge. PLo S Negl Trop Dis.7: e2302
9. Krishna S, Dutta TK, Vinod KV.Clinical profile and complications of neurotoxic snake bite & comparision of two regimens of polyvalent anti- snake venom in its treatment; Indian J Med Res 145, Jan 2017,pp58-62
10.Watt MD, Theakston DRG, Hayes CG, et al. Positive response to endrophonium in patients with neurotoxic envoming by Cobras( Naja naja philippinensis). N Engl J Med. 1986;325:1444-1448