Two case reports of deadly Himalayan bites with tertiary level care: A snake and a possible scorpion.

In the Himalayan region, there is a prevalence of unknown bites (not much data except media) including snakes with high range of mortality among victims because hilly terrain leads to delay in transportation and delayed initiation of proper treatment due to lack of developed tertiary care centers. These bites can present from local hypersensitivity reactions to neurological, cardiological, respiratory, hematological, musculoskeletal, and renal manifestations. We highlight two cases that presented with delayed and varied manifestations, recovered but delayed with dedicated supportive care. A 25-year-old female presented 3 days after bite from an unknown snake, possibly krait, developed cardiotoxicity, neuroxotoxicity, rhabdomyolysis, and hemolytic features and was managed with antivenom and anticholinesterase therapy along with medroxyprogesterone to facilitate recovery from bite-associated neurotoxicity. A 75-year-old male subjected to an unknown bite possibly a scorpion developed shock which was most likely cardiogenic in nature secondary to toxin and was managed initially using inotropic support. Prazosin was started, and he recovered completely though at a later time. Hence, apart from krait bite presenting as multisystem involvement, anticholinesterase and medroxyprogesterone acetate are vital for survival. Similarly, prazosin has a vital role in the recovery of scorpion bite-induced cardiotoxicity. Many such unknown venomous bites go unreported. Further case studies and case reports are necessary to help redefine the epidemiology of such bites in the Himalayan region that poses a diagnostic and therapeutic challenge.

INTRODUCTION

In Uttarakhand, there is a high possibility (not much literatures except media reports as described below) of venomous animal bites in the Himalayas (being a hilly area), especially unknown snake types which have a very deadly presentation ranging from neuroparalytic symptoms to cardiotoxicity. Furthermore, there are increasing incidences of unknown bites, other than snakes, which lead to a high range of mortality among victims. Making a correct diagnosis and initiation of treatment at the earliest plays an important role in managing such unknown bites, but Uttarakhand being a hilly area, there are difficulties associated with transportation, and hence, most victims present to the tertiary care centers usually late or not at all. Another problem associated with these bites is their varied manifestations, which may be sometimes delayed for days that pose a diagnostic challenge.

Most of the snake bite victims are in the age range of 21–30 years with krait (45.23%) followed by cobra (25%) as the most common snake types, and majority of the victims are admitted between the 2nd and 6th day with a mortality rate of 8.33% with respiratory cause being the most common cause of death.[1] In the absence of nearby hospital, many people resort to local indigenous treatment from the so-called Vish vaidyas who use medicinal plants to treat snake bite, scorpion bite, and dog bite.[2] The outcomes of these treatments are not always favorable, for example, in 2016, 42 people died in Rudrapur (in Uttarakhand) due to snake bites, due to lack of antivenom in the right time and the right place.[3] There is a scarcity of data on these bites due to the lack of reporting these cases in the literature (only available in newspapers).[3] There are still many unknowns regarding presentations and therapeutic approaches of all these bites in the holy Himalayas.

We report two cases of deadly Himalayan bites – a snake bite where the victim had neurohemolytic features with associated cardiotoxicity and a probable scorpion bite resulting in cardiogenic shock where comprehensive critical care in a tertiary hospital resulted in a favorable outcome for the patient.

CASE REPORTS

Case 1

A 25-year-old female presented with a history of a snake bite 3 days before the presentation over her right lower limb below the knee. There were two closely set puncture marks from the fangs of the snake. The snake was described as 1.5–2 feet in length, black in color with yellowish stripes on the body. She came home and put a nick mark with a blade (unknown sterility) over the puncture wounds. She was asymptomatic for 3 days when she developed ptosis, diplopia, and limb weakness, which was sudden in onset and progressive in nature. She visited a local hospital where she was administered 10 units of antivenom, but her diplopia did not subside. She additionally developed hematuria and respiratory distress for which she was referred to a tertiary care center for more specialized care.

On examination, she was tachypneic with the use of her accessory muscles of respiration and had a respiratory rate of 32/min. There were no other chest findings explaining the cause of her breathlessness. Single breath count per minute was 12. Her neurological examination revealed bilateral ptosis, diminished reflexes, decreased muscle tone, and decreased strength. The remainder of the examination was unremarkable.

Initial assessment of the patient and her arterial blood gas (ABG) analysis showed type 2 respiratory failure due to respiratory paralysis by neurotoxic snake bite. Whole blood clotting time was performed and was normal. Because of the report of hematuria, confirmed with urine routine and microscopy, serum lactic dehydrogenase level was sent and found to be significantly elevated at 10,120 units/L (normal range, <248 unit/L). There was a fall in the hemoglobin level from 16.5 g/dL to 12.1 g/dL during the 2 days' hospitalization. Liver function tests showed marked transaminitis (serum glutamate-pyruvate transaminase, 3690 U/L; serum glutamic oxaloacetic transaminase, 4100 U/L). The creatine phosphokinase (CPK) and N-acetyl-cysteine level increased to 11,880 units/L (normal range, 39–308 U/L). All of these findings confirmed rhabdomyohemolysis. Her CPK-myocardial band and pro-B-type natriuretic peptide level were also found to be abnormally high confirming cardiotoxicity.

On day-1, due to progressive symptoms, she was given 10 vials of antivenom again. Simultaneously, she was started on neostigmine infusion @1 mg/h after bolus of 2.5 mg intramuscular (IM) along with atropine. Ptosis and single breath count were monitored. However, nothing had improved, and neostigmine was stopped after 12 h. On day 2, her respiratory distress increased, oxygen saturation started to fall, and her sensorium became altered. She was intubated. Chest X ray showed opacity in the right lower lobe which could have been either consolidation or right lower lobe collapse. Computed tomography was performed and it revealed right basal lobe atelectasis with minimal pleural effusion which was mostly secondary to the underlying collapse of lung segments. Empirical antibiotics (ceftriaxone and clindamycin) were administered in view of increased leukocyte counts and basal lung atelectasis considering aspiration pneumonitis and collapse. Neostigmine infusion along with atropine was again restarted considering possibility of delayed response. On day 3, her sensorium started improving and she was put on pressure support ventilation. After giving spontaneous breath trial, she was extubated on day 4. The patient had a persistent bradycardia for which cardiology was consulted. She was placed on a Holter monitor that suggested frequent episodes of atrial and ventricular premature contractions with runs of bradycardia and tachycardia [Figure 1a-c]. This was presumed to be a cardiotoxic effect of the envenomation (or perhaps reaction to the antivenom). The dose of neostigmine and atropine were adjusted according to the patient's heart rate without compromising the recovery from neuromuscular weakness. Repeat ABG analysis suggested persistent CO2 retention due to basal atelectasis and weakness. On day 5, she was given incentive spirometry along with chest physiotherapy. She was given medroxyprogesterone to improve her respiratory drive. Neostigmine was gradually tapered and stopped. She became symptomatically better on day 10. Her respiratory muscle weakness improved and she maintained oxygen saturation without need for supplemental O2. Her repeat chest X-ray showed resolution of the collapse lung segment. Her repeat biochemical laboratory investigations also returned to a normal level. She was discharged on day 13 of hospitalization with a final diagnosis of possible snake Krait bite with cardio-neuro-rhabdomyo-hemotoxicity with delayed response to neostigmine.

Figure 1

Holter images of the case 1: (a) Single ventricular premature complex along with sinus tachycardia. (b) Sinus bradycardia. (c) Atrial premature complexes along with sinus bradycardia

Case 2

A 75-year-old male, nonsmoker, nonalcoholic, presented after a visit to the temple was subjected to an unknown bite possibly from a scorpion. The bite occurred on his left hand and was followed by multiple episodes of vomiting for 1 day and progressive pain, redness, and swelling over the bite mark on the left hand. The patient suddenly developed dizziness on day 2 and was brought to our tertiary care center.

On examination, the patient was drowsy with a blood pressure of 70/50 mmHg, pulse – 70/min, and relative risk – 34/min with the use of accessory muscles. Hand examination demonstrated swelling in the left hand with surrounding tender erythema. The remainder of the physical examination was unremarkable except for bilateral wheezes on the chest auscultation.

He was suspected to have delayed anaphylactic shock due to scorpion stings and given IM adrenaline start followed by infusion. A tetanus injection was given. Empirical antibiotics and adequate fluid replacement were also started in view of the local swelling and suspected infections and sepsis. His hemogram showed neutrophilic leukocytosis with a white blood cell – 17,880 cells/mm3 (neutrophilic). A possibility of septic shock was kept in a place, and he was given injection hydrocortisone 50 mg QID. Kidney function tests suggested a prerenal acute kidney injury. His liver function tests and serum electrolyte levels were normal. Adrenaline infusion caused large erythematous blebs and a local reaction [Figure 2a]; hence, this was changed to a noradrenaline infusion. The tachypnea persisted along with bilateral wheeze and hypotension. The patient remained hypotensive, and hence, the patient was started on a tablet of prazosin 2 mg (0.03 mg/kg/dose) QID in suspicion of cardiogenic shock after the bite from the scorpion. His respiratory distress subsided in the next 24 h along with tapering off noradrenaline. Culture and sensitivity report of the pus obtained from the swelling showed the growth of Acinetobacter and antibiotics were changed according to the sensitivity. Despite this, the swelling increased in size and developed a large ulceration. It was debrided [Figure 2b]. The patient's general condition was improved. He was transferred to burns and plastic surgery department, where he underwent full-thickness skin grafting. He was discharged on day 24 of his hospitalization with a diagnosis of possible scorpion bite with cardiotoxicity and local wound with sepsis. He is doing well with regular follow-up appointments in the plastic surgery department for the assessment of the graft.

Figure 2

Hand and leg images of the case 2: (a) Postscorpion bite debrided wound over dorsum of hand. (b) Multiple large blebs developed after adrenaline infusion in leg

DISCUSSION

With management at tertiary care medical centers, both patients survived from unknown severe venomous bites. One patient suffered from krait bite with major organ impairment and another from a possible scorpion bite with cardiogenic shock. Death from such poisonous bites is very common in the Himalayan and Sub-Himalayan region, however, rarely reported. Due to under reporting of cases reference was taken directly from newspaper article.[3] The major reason of death is lack of proper facilities for the treatment of such cases. There are only very few tertiary centers having comprehensive treatment facilities and access to antivenom. Even antivenom is not routinely available round the clock. This tertiary hospital is the first such center in this region. It is the hope with time that many such potentially deadly cases due to venomous bites will be taken care of at this center.

Snake venom contains a variety of toxins. Elapidae (cobra, krait) mainly causes neuroparalysis, hydrophidae (sea snake) causes rhabdomyolysis, and viperidae (Russell's viper, saw scale viper) causes hemolysis. Paralysis, hemolysis, and rhabdomyolysis usually occurs following the bite of Russell's viper in the Indian subcontinent.[4] Cardiotoxicity in the form of myocardial infarction and arrhythmia can occur following a viper bite.[5] The description provided by the patient herself in the first case most probably resembles the bite of a krait. Hence, Himalayan krait bite may present with myotoxicity, hemotoxicity, cardiotoxicity, and neurotoxicity in this single patient. The α- and β-bungarotoxin of krait mainly inhibits the release of acetylcholine causing paralysis, but cases have been reported with the possibility of pulmonary edema along with ventricular fibrillation and also fulminant myocarditis.[67] Phospholipase A2 of bungarus has been studied to cause hemolysis by lysing the phospholipid cell membranes of red blood cells in vitro.[8] Cases have been reported from Malaysia where the krait bites result in rhabdomyolysis.[9]

Another interesting fact of the first case was the delayed presentation after the initial krait bite. The preparalytic phase following a snake bite is as long as 12 h,[1011] but in our case, the victim developed these symptoms 3 days after the bite and initiation of antivenom. After antivenom was started, the patient responded and recovered completely. The reasons for this varied presentation and response to treatment are not known. Anticholinesterases like neostigmine when given with atropine has a definite role in cobra bites, but it is ineffective in other neurotoxic snake bite like krait whose toxins mainly act on presynaptic receptors.[1213] Even in this case despite starting neostigmine infusion at higher doses than which is recommended, the patient breath count did not improve (but was not deteriorating), and hence, the infusion stopped. However, soon the patient went again into type 2 respiratory failure and required mechanical ventilation. As a result, neostigmine was restarted, and the patient's respiratory function improved gradually. Moreover, everything was delayed in this case, including a delayed presentation and a delayed treatment response. The reason for this delayed presentation of snake bite and delayed response to neostigmine could not be ascertained, and there is a need for further investigations to ascertain the types of toxins in Himalayan krait venom and how they are different from other kraits and possible new approaches in management. Since the patient was having persistent bradycardia secondary to cardiotoxicity, the dose of neostigmine and atropine was adjusted without compromising the recovery from neuromuscular weakness. Even after weaning the patient, residual weakness remained and she developed right basal atelectasis. Medroxyprogesterone was used as a respiratory stimulant in this patient and chest physiotherapy was performed in view of residual muscle weakness. Gradually the respiratory drive and effort increased thus suggesting possible role of respiratory stimulant in aiding recovery from paralysis secondary to neurotoxic snake bite.

Scorpion bites are common in the Himalayan region, particularly in the rural areas. Although local symptoms including severe pain and burning sensation at the site of sting are most common manifestations, systemic complications can ensue.[14] Indian red scorpion venom (α toxins) delays the closing of neuronal sodium channels stimulating autonomic centers: sympathetic and parasympathetic, leading to autonomic storm.[15] Although scorpion antivenom is a specific antidote, it is not helpful to reverse the cardiovascular effects of venom and effects of venom-induced liberated pharmacological agents. However, prazosin, a pharmacological and physiological antidote to venom actions, remains a main drug of choice.[16] In this case the patient shock did not responded initially to use epinephrine/norepinephrine but use of prazosin facilitated in recovery.

Mortality associated with venomous bite is very high in India. When examining the state of Uttarakhand in India, the rate further increases. There are three main reasons behind this phenomenon (1) lack of adequate tertiary care hospitals that can provide comprehensive treatment and care for such victims, (2) hilly terrain that delays timely transportation of these victims, and (3) local indigenous practices that believe in herbal medications in the treatment of these victims. Moreover, there are many unexplored species of snakes and other venomous species in the Himalayas whose bites go unreported and there is lack of information about the wide clinical spectrums associated with these bites.

Both these cases show a wide spectrum of clinical manifestations of these deadly venomous bites; these cases of deadly bites which, although rare, can be difficult to manage without resources such as those at tertiary level institutes to ensure good clinical outcomes. Certain novel treatment strategies can be adopted when dealing with such rare manifestation as demonstrated by these two cases. There is a need for a proper referral system for transferring these patients to centers of excellence along with education to the general public about outcomes associated with these bites if proper treatment facilities are availed at the right time.

Both patients were victims of deadly Himalayan bites, and early institution of tertiary level comprehensive care improves the mortality and morbidity associated with these injuries. There is a need for more tertiary centers along with strengthening of the referral system so that the victims can be saved when proper care is initiated early. Himalayan krait bite can present with all multisystem organ toxicity. Anticholinesterase is vital for the survival of neurotoxicity by krait bite despite a delayed response. Prazosin and medroxyprogesterone acetate are vital in the recovery of scorpion bite-induced cardiotoxicity and krait bite-induced neurotoxicity, respectively.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.