Fatal intracranial bleedings in a viper bite: A case report

Abstract

Viper bite envenomation represents a significant occupational hazard among agricultural workers in India. The viper bite envenomation is usually suspected when a patient presents with predominant local symptoms at the bitten site, including pain, swelling, and necrosis. Further, systemic findings such as diffuse intravascular coagulation, hypotension, and shock may alert physicians of viper bite envenomation rather than a neurotoxic snake bite. However, cerebral complications are rare in viper bites but may potentially fatal. Central nervous system involvement in a viper bite is either due to neurotoxins or hemorrhagins present in the venom, which may induce cerebral thrombosis, ischemia, infarction, and hemorrhage. Here we present a case of a previously healthy adult male who succumbed to extensive subarachnoid, intracerebral, and intraventricular hemorrhages involving bilateral cerebral hemispheres following viper snake bite envenomation. This report highlights the importance of anticipating cerebral complications in viper bite envenomation, a rare occurrence. It also emphasizes the need for early antisnake venom administration to prevent and control systemic envenomation and its complications.

Introduction

Snake bite deaths remain a significant occupational, domestic, and environmental health hazard among breadwinning male population of 25–55 years in developing and tropical countries.¹ Recent global estimates reveal that out of 2.5 million snake bite envenoming cases, approximately 81,000–138,000, die in a year, and unfortunately, more than half of these deaths occur in India.^1,2 In line with this, WHO recategorized snake bites as the priority neglected tropical disease and aims to halve snake bite deaths by 2030.^2,3

In India, the majority of the snake bite envenomation are caused by the following four snakes: Indian cobra (Naja naja), Indian krait (Bungarus caeruleus), Russell's viper (Daboia russelli), and saw-scaled viper (Echis carinatus). They are infamously known as ‘Big Fours’. ⁴ Among them, vipers cause the majority of snake bites in India.² Viper bite is characterized by predominant local symptoms such as pain, swelling, and necrosis at the bite site. Besides, it also results in systemic manifestations like consumption coagulopathy, acute renal failure, acute respiratory distress syndrome, hypotension, shock, etc.⁵ However, cerebral complications are rare following viper bites but are potentially fatal to cause death. Here we report a case of multiple fatal intracranial bleedings, consisting of intracerebral hemorrhage, subarachnoid hemorrhage, and intraventricular hemorrhage besides local manifestations following a viper bite.

Case report

Alleged history

An unidentified snake bit a previously healthy male farmer, 42-year-old, on the left foot while he was returning home from his paddy field around 4:00 p.m. He developed pain and mild swelling on the left foot following the bite, and then was shifted to a nearby primary health care center and thereafter to the district government hospital. After careful physical examination, the medical officer ruled out the systemic envenomation and did not administer the antivenom as there are no signs and symptoms except pain and mild swelling at the bite site. His 20-min whole blood clotting test (WBCT20) was normal (blood was clotted) at the time of admission. However, his symptoms started worsening after 4 h with complaints of altered sensorium, nausea, vomiting, increased thirst, giddiness, chest pain, and sweating. Hence, he was discharged against medical advice and admitted to our tertiary care hospital for further management on the same day at 10:00 p.m. (about 6 h post-bite).

Clinical findings

On admission, he was drowsy with altered sensorium, and his vitals were as follows: Glasgow coma scale score 14, blood pressure 160/90 mmHg, respiratory rate 30 per min, the pulse rate 136 beats per min, and SpO₂ 98% at room air. His WBCT20 was positive (not clotted). The laboratory workup revealed the following: haemoglobin 141 g/L, pH 7.47, PO₂ 25.2 mmHg, PCO₂ 24.0 mmHg, HCO₃ 19.7 mmol/L, sodium 131.5 mmol/L, potassium 2.97 mmol/L, chloride 108 mmol/L, and lactate 2.1 mmol/L. Gross haematuria was noted in the urine bag after catheterization.

Local examination of the bitten part (left foot) revealed profound swelling, tenderness, oozing of the blood from the alleged bite mark. Ten vials of polyvalent antisnake venom effective against ‘Big Four’ Indian snakes were administered approximately 6 h after the bite along with antacids, antiemetics, antibiotics, and prophylactic tetanus toxoid. He was intubated and put on mechanical ventilation after becoming unconscious and further clinically deteriorated. Noncontrast CT of the brain revealed multiple intracerebral hemorrhages in both cerebral hemispheres with surrounding edema and midline shift (Fig. 1). He succumbed to the envenomation despite resuscitative efforts after about 14 h of snake bite. The body of the deceased was sent to the mortuary for post-mortem examination.

Fig. 1.

Noncontrast CT images of the brain displays multiple intracerebral hemorrhage involving bilateral cerebral hemispheres.

Autopsy findings

The external examination has revealed 2 fang marks (punctured wounds) at a distance of 1 cm on the inner aspect of the left foot with edema and purplish discoloration of the surrounding area. Blood was oozing out on pressure from the fang marks. On dissection, the underlying layers of the skin and muscles were ecchymosed. Internal examination of the skull cavity showed an oedematous brain with diffuse, thin-layered subarachnoid hemorrhage over bilateral cerebral hemispheres and cerebellum (Fig. 2). Intracerebral hemorrhage of about 200 mL was present in the bilateral frontoparietal-temporal lobes (Fig. 3). A hemorrhage of about 50 mL was present in the third and fourth ventricle. The abdominal cavity exhibited multiple petechial hemorrhages on the inner aspect of the peritoneal wall and beneath the capsule (subcapsular) on the anterior surface of the right and left lobe of the liver. Both kidneys were markedly congested. Histopathological examination revealed acute tubular necrosis of the kidneys, denudation of the wall, congestion, hemorrhages of the stomach wall mucosa, and hemorrhage, congestion, and necrosis of dermis at the bite site.

Fig. 2.

Gross picture of the brain with meninges illustrates the diffuse subarachnoid hemorrhage on the bilateral cerebral hemispheres with the exception over right frontal and left parietal lobes at places.

Fig. 3.

Gross picture of the right cerebral hemisphere shows multiple intracerebral hemorrhages involving right (A) and left (B) cerebral hemispheres.

Given the history, clinical presentation, and autopsy findings, along with histopathological examination, the cause of death was ascertained to be intracerebral hemorrhage and its complications as a result of viper bite envenomation.

Discussion

Viper venom is a complex mixture of enzymes that include proteolytic enzymes, polypeptide toxins, proteases, phospholipases, collagenases, thrombin-like enzymes, etc.⁶ The interaction between these anti-coagulants and procoagulant enzymes (metalloproteinases and serine proteases) in their venom are responsible for venom-induced consumption coagulopathy and hemorrhagin-induced direct endothelial injury. This results in hemorrhage in various organs, including intracranial bleedings.7, 8, 9, 10 This explains the possible mechanism of fatal intracranial bleedings in the present case. Further, snake venom metalloproteinases also trigger hemorrhage by degrading type IV collagen of the capillary basement membrane and disrupting the cell-to-cell adhesion of vessel endothelium.¹¹

Pain at the bite site is the earliest symptom following the viper bite, which precedes swelling, blister formation, and necrosis.¹⁰ Also, coagulopathy and platelet dysfunction following viper bite cause spontaneous and persistent bleedings from various systemic organs and at the bite site.¹² Neurological or neuromuscular manifestations such as ptosis, blurred vision, ophthalmoplegia, strabismus, and diplopia are most commonly reported following Sri Lankan and South Indian Russel's viper bite.^13,14 These neurological manifestations were absent in the present case due to the lack of neurotoxins present in the venom of East Indian Russel's viper. In the present case, the elevated blood pressure on admission and concentric hypertrophy of the left ventricle at autopsy suggests the possibility of undiagnosed hypertension, which could also potentially contribute to intracranial bleeding. However, this possibility is ruled out by the absence of bleeding at the basal ganglia, thalamus, and pons, the preponderance sites for hypertension-induced intracerebral hemorrhages.¹⁵

Identification of the snake species concerning venomous and non-venomous is paramount in the management. It is usually achieved by detailed history from the patient or onlookers, species identification from the snake which might be killed and brought to the hospital or from photographs of the snake, examination of the fang marks, or through local and systemic manifestations. The treating physicians should not hesitate to get help from forensic toxicologists or herpetologists if any difficulties to identify the snake species. Once the diagnosis of venomous snake is made, the examination for signs and symptoms of local and systemic envenomation should be carried out (syndromic approach). Given the history of snake bite at the paddy field, during the daytime, concomitant profound local symptoms, and prolonged WBCT20, the envenomation in the present case is ascribed to Russel's viper bite.²

Clinically, the WBCT20 is the standard method to diagnose the viper bite envenomation. In addition, prolonged prothrombin time and activated partial thromboplastin time, coupled with elevated fibrin degradation products and D-dimer levels, are indicators of severe consumption coagulopathy or disseminated intravascular coagulation following viper bite.¹¹ In unknown snake bite cases, immunodiagnostic tests play a crucial role in identifying snake venom antigens in the serum, thus facilitating the indirect identification of the snake.¹⁰ Enzyme-linked immunoassay and radioimmunoassay are the preferred methods for qualitative and quantitative analysis of the venom in clinical and forensic settings.¹⁶ However, this is usually not done in most health care settings of India and not done in the present case as there was a consensus made on the diagnosis of viper bite from the history and clinical manifestations. CT and MRI are valuable tools in detecting intracranial hemorrhages.

Ignorance and lack of awareness about specific approved and obsolete first aid methods cause an undue deleterious impact on the outcome of the victims in developing countries. After a snake bite, the most preferred first aid methods are reassurance of the victim, pressure immobilization of the bitten limb, non-interference of the wounds at the bite site, and immediate referral to the nearby hospital.¹⁷ The undue delay in the initial presentation at the primary health center along with post-bite ambulation (walking for an ample distance from the field to home) might have increased the severity of envenomation in the reported case.

Antisnake venom (ASV) is the only scientifically validated treatment against snake bite envenomation. It should be given as soon as possible when envenomation is clinically established. The administration of ASV is indicated when: profound local findings include severe pain, swelling, and gangrene; signs of systemic envenomation, for example, ptosis, ophthalmoplegia, respiratory paralysis (neurological); bleeding from various organs and mucous membranes, or clinical evidence of hemostatic abnormalities (consumptive coagulopathy); hypotension and shock (cardiovascular).¹⁷ Delayed administration of antivenom could be futile in cases with cerebrovascular complications.^10,18 In the present case, the ASV was administered 6 h post-bite. Though he presented to the first hospital (primary health care) within 2 h post-bite, the ASV was not given as no indications were present except minimal swelling and pain at the bite site. His WBCT20 was also within normal limits at primary and district level hospitals. Hence, ASV was deferred considering the risk-benefit ratio, as ASV itself can result in life-threatening anaphylactic reactions.

Further, the sudden deterioration in his condition (altered sensorium and worsening local symptoms) made the relatives get him discharged from the district hospital against medical advice and transferred to our tertiary care hospital. Individual variations, age, and other comorbidities of the victim, bite site, snake's size, dry bite, season, etc. may significantly influence the signs, symptoms, and their onset following snake bite.⁵ Prompt administration of ASV after eliciting the signs of envenomation at the district hospital would have effectuated the better prognosis in the present case.

Lack of trained human resources coupled with apprehensions in the administration of ASV, fearing possible adverse reactions by the primary treating doctor at primary health care are the major hindrances in managing snake bite cases at an earlier stage in India.¹ In addition, by the time envenomation is confirmed through the syndromic approach, most of the venom might be bound to tissues and make the neutralization implausible by antivenom.⁵ Development and utilization of a snake venom detection kit is paramount in the early and immediate treatment of snake bite victims.¹ Prompt neurosurgical interventions, for example, a craniotomy, may be needed to evacuate extensive intracranial hemorrhage and relieve associated edema and intracranial tension.¹⁹ However, the neurosurgical interventions are most often deferred until the ongoing hemostatic abnormalities get improved.

Ehelepola et al.²⁰ reported a case of intracranial hemorrhage including subarachnoid hemorrhage, and intraventricular hemorrhage due to alleged Russel's viper envenomation from Sri Lanka. In their report, the patient was initially treated by an indigenous doctor and was admitted to a teaching hospital 24 h of post-bite. The victim had profound local and systemic (hematological, cardiac, neurological, and renal) abnormalities and died 48 h post-bite because of the late administration of antivenom (24 h post-bite) coupled with the unavailability of an intensive care bed to provide aggressive management. In contrast to their report, the present case had no neuromuscular symptoms such as bilateral ptosis and ophthalmoplegia. Also, the hospital admission time is around 6 h post-bite. Polyvalent ASV is administered on admission, and he was intensively managed as per protocol, including mechanical ventilation. Despite this, he succumbed to the envenomation because of extensive intracranial bleeding.

In conclusion, fatal cerebral complications can result from viper bite envenomation, though extremely rare. The treating physicians should be vigilant and watchful for cerebral complications in addition to other systemic and local findings in viper bite. Given the significance of early detection of snake species, it is recommended that snake venom detection kits in primary or district hospitals be made available to scale down fatalities. This report also stressed the prompt administration of ASV upon the signs and symptoms of envenomation by trained staff at primary health centres and district hospitals to reduce morbidity and mortality. Because they are the first contact healthcare systems for most victims in developing countries like India. Special attention should be given to creating awareness and mass education among vulnerable populations, especially farmers, about identifying snakes, appropriate & prohibited first aid measures, early and effective treatments available such as ASV in nearby hospitals.

Funding

Nil.

Ethical statement

Informed consent from the legally authorized representatives of the deceased has been obtained.

Declaration of competing interest

All authors declare that they have no competing interests.

Author contributions

Conceptualization: Alagarasan Naveen, Manas Ranjan Sahu, and Manoj Kumar Mohanty. Literature search & review, and manuscript writing: Alagarasan Naveen, Manas Ranjan Sahu. Data curation: Alagarasan Naveen, Kimi Soumya Padhi. Investigation: Autopsy done by: Alagarasan Naveen, Manas Ranjan Sahu, Kimi Soumya Padhi. Review and editing: all authors. Manuscript approval: all authors.