Neuromuscular Effects of Common Krait (Bungarus caeruleus) Envenoming in Sri Lanka
Abstract
We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response.
Methodology
Patients with definite common krait (Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6wk and 6–9mth post-bite.
Principal Findings
"There were 33 patients enrolled (median age 35y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20–32h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5h post-bite (2.8–7.2h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12h. sfEMG abnormalities gradually improved over 24h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96h post-bite (54–216h). On discharge, median 8 days (4–12days) post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6wk post-bite. There were no clinical or neurophysiological abnormalities at 6–9mth.
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"All patients with suspected krait envenoming had a complete neurological examination on admission to hospital, then repeat examinations every 2h for the first 24h post-bite, and then every 4h for the remainder of their hospital stay. After discharge patients had a full neurological examination at six weeks and six months post-bite to detect residual neurological impairment. The Medical Research Council scale for muscle strength[18] was used wherever appropriate. For the assessment of respiratory muscles, tidal volume was measured using a spirometer. Ptosis was graded from grade I to III using a visual analogue scale, with complete ptosis being grade III. Weak or sluggish eye movements in one or all directions was considered to be partial ophthalmoplegia and absent eye movements in all directions, complete ophthalmoplegia. At each time point patients were specifically examined for features of autonomic neurotoxicity (heart rate, blood pressure, lacrimation, sweating and salivation), central effects (level of consciousness and occulocephalic reflexes) and myotoxic effects (muscle pain and tenderness, both local and general).
Clinical assessments were done by one author (AS) or medically qualified clinical research assistants. All assessments performed by clinical research assistants were reviewed by AS and approximately one third were reviewed by another medically trained author (SS). In addition to a neurological assessment, all patients had a full clinical examination on admission, at 12h and 24h post-bite, and then daily until discharged. Local effects included pain, swelling, paraesthesia or regional lymphadenopathy and non-specific systemic effects were defined as headache, nausea, vomiting or abdominal pain. All assessments were recorded using a pre-formatted clinical data form.
Antivenom administration was decided by the treating physician. All patients who received antivenom in this study received 20 vials of Indian polyvalent antivenom as the first dose from VINS Bioproducts (batch numbers: 01AS11119, 01AS11121, 01AS13100, 01AS14025, 01AS14026, 01AS14035). No patient in this study received a second antivenom dose. The antivenom infusion was ceased briefly for 5–10min in patients who developed anaphylaxis. Antivenom reactions were treated according to the attending physician with adrenaline, antihistamines and corticosteroids.
During review visits patients had a routine physical and neurological examination. They were also questioned specifically about the presence of neuromuscular effects that prevented them performing routine daily work, and about any recovery of local effects.
Patients were classified into three groups based on the presence and severity of neurotoxicity. The first group included patients who developed no clinical evidence of neurotoxicity. The second group was patients with mild neurotoxicity defined as the presence of one of the following clinical features; ptosis, ophthalmoplegia or facial muscle weakness, but not bulbar, respiratory or limb weakness. The third group was severe neurotoxicity defined as patients developing paralysis that involved bulbar and respiratory muscles requiring mechanical ventilation."
"During the study period 773 snakebite patients were admitted and 38 of these were suspected common krait bites. Thirty one patients had the offending snake positively identified as a common krait and two others were positive for krait venom in their blood. The remaining five cases were only suspected common krait bites based on circumstances of the bite, but had no features of local or systemic envenoming, despite having fang marks. None of these patients had a previous history of neurological disorders or therapeutic agents known to cause neurotransmission abnormalities. Table 1 provides the demographic features of the 33 confirmed cases of common krait bites."
link to image"Seventeen patients developed severe neurotoxicity with a range of neurotoxic clinical features on admission (Table 2). Three patients appeared to have altered consciousness and had no respiratory effort on admission with oxygen saturations < 50%. These three were immediately intubated and ventilated. All 17 patients were given antivenom a median of 3.5h post-bite (2.8–7.2h). Antivenom therapy did not stop progression of neurotoxic features in any patient and intubation and mechanical ventilation was required within 7h of the snake bite in all 17 patients. The clinical features of neurotoxicity progressed in a descending order from eyes to peripheral limbs (Fig 2A). Five patients developed complete limb paralysis with areflexia occurring within 8h of the bite (Figs 1C and 2A)."
link to image"In this cohort of patients with definite common krait envenoming, about half developed life-threatening neuromuscular paralysis that did not appear to be prevented by or respond to antivenom treatment. Patients who had sfEMG performed had increased jitter and increased neuromuscular block that correlated with the clinical severity. The neurophysiological abnormalities improved in line with clinical recovery but were still abnormal 6 weeks after the bite, despite the patients being clinically normal. The prolonged high jitter during the recovery phase may represent immaturity of the motor nerve terminals undergoing the re-innervation process. Excepting the three patients who were intubated due to antivenom reactions, all other patients were intubated due to bulbar weakness and/or respiratory paralysis, which developed within 7h of the bite. This demonstrates that severe neuromuscular paralysis develops rapidly. Based on this finding it appears that patients who do not develop bulbar weakness or respiratory paralysis within 12h of the bite, are highly unlikely to develop severe paralysis. These figures are largely in agreement with previous reports from Sri Lank"
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