Introduction

    Sri Lanka is home to four species of snakes in the family Viperidae. They can be divided into 2 groups: true vipers and pit vipers. True vipers include Russell’s viper (Daboia russelii) and the saw scaled viper (Echis carinatus), and pit vipers include the hump-nosed viper (Hypnale spp.) and Sri Lankan Green pit viper (Trimeresurus trigonocephalus). Of these 4 species, Russell’s vipers and hump-nosed vipers are deadly venomous and are included in the WHO Category 1 classification of snakes, meaning antivenom is required [1]. In Sri Lanka, Russell’s viper is responsible for 30-40% of all venomous snakebites [2] and the majority of deaths are caused due to its bite [3]. Its envenoming causes systemic manifestations such as venom-induced consumption coagulopathy (VICC), neuroparalysis and acute kidney injury (AKI) [4],[5]. There are three broadly classified pulmonary manifestations in snakebites: generalized neuromuscular paralysis affecting airway and respiratory muscles, pulmonary edema, and pulmonary hemorrhage or thrombosis due to VICC [6]. Respiratory paralysis and pulmonary edema are due to either elapid [7] or, rarely, viper bites, [4] whereas VICC complicating pulmonary hemorrhage are widely caused by viper envenoming. We report a patient who presented with neuroparalysis, AKI and severe form of VICC, which manifested as pulmonary hemorrhage and hematuria, following a Russell’s viper bite. The patient completely recovered after 23 days of treatment including intensive care management.

Case presentation

    A 30-year-old previously well, married male was transferred from a local hospital to a tertiary care centre for further management of a snakebite. He was bitten by a snake around 1930 h on his left foot while walking on a footpath and the snake was identified as Russell’s viper. On admission, he had mild local pain, moderate swelling and two fang punctures on the dorsum of foot, 17 mm apart (Figure 1). Twenty minutes whole blood clotting test (WBCT20) was negative (

      As he developed vomiting with bilateral ptosis and external ophthalmeplegia 2 hours after the bite, he was administered 20 vials of polyvalent antivenom after giving intravenous hydrocortisone 400 mg, chlorpheniramine 10 mg and subcutaneous adrenaline 0.25 mg as bolus doses. Halfway through the antivenom infusion, he developed shortness of breath, rhonchi in the lungs, low blood pressure (BP 84/62 mmHg) and bradycardia (heart rate 42 beats/min). Immediately, antivenom infusion was stopped and adrenaline 0.5 mg was administered intramuscularly. After vital parameters became normal, the infusion was restarted. His WBCT20 was positive 3 hrs after the bite, and was associated with hematuria. He developed respiratory failure around 6 hrs post bite with low oxygen saturation, shortness of breath, restlessness and bleeding from gums. He was immediately intubated, another 10 vials of antivenom were started and he was transferred to the intensive care unit for mechanical ventilation. There was laryngeal edema associated with bleeding seen during intubation.

     He was kept on synchronized intermittent mandatory ventilation (SIMV) mode with sedation and paralysis for 48 hrs. On day 2, another 10 vials of antivenom were administered due to persistent incoagulable blood associated with blood stained endotracheal tube secretions. On day 2, patient developed ischemic changes on his ECG (T wave inversions on V₁-V₅) and the 2D-echocardiogram showed 45% ejection fraction with global hypokinesia. He also had oliguria associated with elevated blood urea and creatinine levels (Figure 2) for which furosemide 5 mg/hour IV infusion was started. WBCT20 was negative from day 3 onwards. Patient was extubated on day 5 after getting T piece ventilation. He then developed hemoptysis. High resonance computed tomography (HRCT) of chest was performed and confirmed pulmonary hemorrhage (Figure 3). On day 9, patient had severe pain in his right leg. A venous duplex study was done and showed deep vein thrombosis (DVT) extending from external iliac vein to popliteal vein, and soft tissue edema in bilateral lower limbs (Figure 4). Low molecular weight heparin infusion (18 IU/Kg/hour) was started for DVT and continued for 3 days and then warfarin 5 mg daily. In addition, clindamycin 600 mg IV 4 times a day and  piperacillin tazobactam 4.5 g three times a day were administered. Laboratory findings throughout hospital stay are shown in Table 1. On day 17, when the DVT was resolved, the patient was transferred to the medical ward. On day 23, he was discharged and followed up in a medical clinic for the DVT.

Discussion

    The life-threatening complications due to VICC caused by Russell’s viper envenoming are intracranial bleeding [8] and pulmonary hemorrhage [9]. The venom of Daboia russelii contains hemotoxins which cause VICC and hemorrhages [10], such as basic coagulant metalloprotease (RVBCMP), snake venom serine proteinase (SVSPs), snaclec (SCLs), and L-amino acid oxidase (LAAOs). RVBCMP is organ specific and has a direct action on lung microvasculature, which leads to pulmonary hemorrhage [11]. The hemotoxins do not induce bleeding equally in all human organs [12] which may be due to differences in the biochemical nature of the vascular wall. In mouse model, the venom has in-vitro hemorrhagic like activity in lungs, liver, kidneys, brain and heart [13]. Pulmonary hemorrhage following snake envenoming is a rare complication and is exclusively due to viper bites. Other snakes that cause fatal pulmonary hemorrhage include Bothrops species endemic to Central and South America [14],[15] and hump-nosed pit vipers (Hypnale hypnale) of Sri Lanka [16].  There is recent evidence of the Australian eastern brown snake (Pseudonaja textilis) causing fulminant pulmonary hemorrhage in dogs [17]. It was found that jararhagin, a metalloproteinase from Bothrops jararaca induces lung hemorrhage [15]. Other pulmonary effects such as acute respiratory distress syndrome (ARDS) and pulmonary edema following snakebites are rarely reported. However, pulmonary edema was found upon autopsy examination following Russell’s viper bites [18] and hump-nosed viper (Hypnale zara) bites [19].

      Pulmonary hemorrhage is acute bleeding or oozing of blood from the respiratory tract. Diffuse alveolar hemorrhage occurs due to widespread disruption of alveolar-capillary basement membranes, which leads to blood collecting within the alveoli. This may clinically manifest as hemoptysis, dyspnea, tachypnea and airspace opacities in radiological images. Our patient on day 1 may have had pulmonary hemorrhage, which could explain why he had bleeding from the laryngeal outlet upon intubation, and blood stained secretions from the endotracheal tube. After extubation on day 5, he also had hemoptysis and HRCT of the chest confirmed the possibility of pulmonary hemorrhage (Figure 2). He had high creatine phosphokinase (CPK) levels, which gradually decreased (Figure 3D), suggesting rhabdomyolysis, a known complication in Russell’s viper envenoming [5]. Also, the patient had elevated levels of creatinine and blood urea (Figure 3C), though normal urine output was maintained with a furosemide infusion. There was no metabolic acidosis seen in arterial blood gas analysis and serum potassium levels were also normal throughout except day 2, therefore, he did not need hemodialysis. Due to pulmonary hemorrhage, hemoglobin level persistently decreased (Figure 3A) and the patient had venom-induced thrombocytopenia (Figure 3B). However, peripheral blood microscopy showed no evidence of microangiopathic hemolysis. He also had cardiotoxic effects manifested as ischemic changes on the ECG and impairment of ejection fraction with global hypokinesia.

   Snakebite has a significant impact on human health and economy through treatment-related expenditures and loss of productivity [20]. Early administration of anti-venom has been accompanied by significant improvement in outcomes [21]. This index case history conveys the deadly nature of viperid snake venom which results in fatal systemic bleeding to vital organs.

Conclusion

Severe fatal systemic manifestations like pulmonary hemorrhage may rarely occur following Russell’s viper bites. These patients need mechanical ventilation with intensive care treatment and prolonged hospital stay. Early elective intubation is beneficial and antivenom is the mainstay of management.

Acknowledgement

We thank Consultant Physicians, Respiratory Physician, Anesthetists, medical officers and staff of Intensive Care Unit, Teaching Hospital, Ratnapura, Sri Lanka.

Conflict of Interest: None to be declared.

Funding and Support: None.