Clinic: Bungarus sp.

Examine for venom effects

Local Effects

• Minimal / absent pain
  Note: A sleeping victim may even not wake up. Most bites happen while sleeping indoors on the ground. 

• Minimal / absent swelling.

Neurological effects

• Descending flaccid paralysis
  • Ptosis (not to be mixed up with tiredness / drowsiness; test: lid retraction with upward gaze)
  • Double vision (external ophthalmoplegia)
  • Difficulties to swallow (dysphagia) (bulbar paralysis) > inhalation of vomitus!
  • Difficulties to lift the head when lying on the back (‘broken neck syndrome’)
  • Cyanosis, shallow breathing, respiratory arrest (respiratory paralysis); respiratory arrest may be precipitated by obstruction of the upper airway by the paralysed tongue or inhaled vomitus.
  • Weakness or loss of voluntary movement; movements of digits may still be possible, allowing the patient to communicate
  • Loss of consciousness and generalized convulsions caused by hypoxaemia in patients who have respiratory paralysis

• Autonomic neurotoxicity
  • Fluctuations in heart rate and blood pressure with periods of severe hypertension
  • severe abdominal pain resembling biliary or ureteric colic
  • paralytic ileus
  • constipation

Muscular effects

• Generalized rhabdomyolysis
  • Muscles pain and tenderness, painful on passive stretching, muscle stiffness, trismus
  • Bulbar and respiratory muscle weakness
  • Dark brown urine.
  • Renal failure
  • Laboratory: Generalized rhabdomyolysis: defined by a serum creatine kinase level > 10,000 U/l
  • ECG: Signs of hyperkalaemia 

Species-specific envenoming pattern

The assessment of the envenoming pattern is based on the data from publication in which the identification of the snakes is clearly specified and in accordance with accepted criteria.

Local effects

¹Absent / mild

²Exception possibly B.niger.

Neurological effects

³Neuromuscular toxicity
Descending flaccid paralysis including respitroty muscles.

⁴Autonomic neurotoxicity

“Symptoms suggesting impaired parasympathetic or increased sympathetic activity have been largely overlooked. In people bitten by a krait (Bungarus candidus, Bungarus multicinctus, and Bungarus caeruleus), there are additional features, such as fluctuations in heart rate and blood pressure with periods of severe hypertension, severe abdominal pain resembling biliary or ureteric colic, paralytic ileus, and constipation. However, these features are difficult to attribute to venom-induced autonomic disturbances in patients who are being mechanically ventilated and given large doses of sedative drugs.” (Warrell and Williams 2023).

Muscular effects

⁵Mild

⁶Myalgia 

⁷Rhabdomyolysis with secondary renal failure

Other effects

Hyponatraemia → Hypotension / shock; brain damage. 

For references on the various venom effects, see 'Species-specific evidence' below.

Clinical management

See also (depending on the origin of the culprit)

Clinical Management: Indian Subcontinent and Southeast Asia

Clinical Management: Far East

for advice on post-First Aid measures, diagnosis (clinical, laboratory) and treatment (supportive, antivenom).

First Aid

Release of any type of tourniquet follow links above.

Local treatment

Pain control
Tetanus prophylaxis
Standard wound care
WHO (2010, 2016) 

Systemic supportive treatment

A general understanding of emergency medicine is required, or can be found in emergency medicine guidelines, e.g. ABCDE approach, WHO-ICRC Basic Emergency Care.

Follow SAMPLE & ABCDE ApproAch

• Comprehensive ABCDE approach

• ICRC Basic Emergency Care: approach to the acutely ill and injured (SAMPLE  and ABCDE approach: first module)

Obey BUNGARUS sp. - specific features

see 

• 'Species-specific envenoming pattern' above

and

• Guidelines for the Management of Snakebites, WHO Regional Office SE Asia

Key issues

Respiratory failure

Lifesaving in neurotoxic krait envenoming (as supportive treatment and when antivenoms are not available or fail):

Airway management
Breathing: Oxygen ⇨ assisted ventilation ⇨ mechanical ventilation

Anticholinesterase drugs to improve neuromuscular transmission

In Krait bites anticholinesterase drugs may fail or are only partially effective (Warrell 2023).

Signs & symptoms of autonomic neurotoxicity

See footnote 4 above.

Rhabdomyolyis

Bungarus niger

Acute kidney injury (AKI)

Secondary to rhabodmyolysis (Bungarus niger)

Specific treatment (antivenoms)

• WHO Snakebite Information and Data Platform

• Guidelines for the Management of Snakebites, WHO Regional Office SE Asia

References

• WHO-ICRC Basic Emergency Care: approach tothe acutely ill and injured (2018)
  https://www.who.int/publications-detail-redirect/basic-emergency-care-approach-to-the-acutely-ill-and-injured
• WHO ABCDE Approach
  https://cdn.who.int/media/docs/default-source/integrated-health-services-(ihs)/csy/bec-quick-cards/becp-edu29-pdf-en-finl.pdf?sfvrsn=2532d61b_2
• WHO (2010) Wound and lymphoedema management. WHO/HTM/NTD/GBUI/20101 I. 2010. https://www.who.int/publications/i/item/9789241599139
• WHO (2016) Guidelines for the management of snakebites. 2^nd edition. https://www.who.int/publications/i/item/9789290225300
• WHO Snakebite Information and Data Platform
  https://www.who.int/teams/control-of-neglected-tropical-diseases/snakebite-envenoming/snakebite-information-and-data-platform
• Warrell DA. Venomous and poisonous animals. In: Farrar J, Garcia PJ, Hotez T, Junghanss T, Kang G, Laloo D (eds.). Manson’s tropical diseases. 24th ed. Elsevier; 2023.
•  Warrell DA, Williams DJ. Clinical aspects of snakebite envenoming and its treatment in low-resource settings. Lancet. 2023 Apr 22;401(10385):1382-1398. PMID: 36931290. https://doi.org/10.1016/s0140-6736(23)00002-8 

Species-specific evidence

Bungarus caeruleus

India

• Bawaskar and Bawaskar (2004)
  23 patients bitten by kraits. Identification: indirect evidence (bite at night whilst sleeping on the floor, abdominal pain, no local signs, neurotoxic signs and symptoms). 4/23 reported with snake available for identification.

Sri Lanka

• Ariaratnam et al. (2008)
  88 patients bitten by B. caeruleus. Identification: morphological 88/88.
• Sethi and Rastogi (1981)
  1 case
• Silva et al. (2016)
  33 patients bitten by B. caeruleus. Identification: morphological or immunological. 8/33 (no neurotoxicity), 8/33 mild neurotoxicity), 17/33 (severe neurotoxicity).
• Theakston et al. (1990)
  5 patients bitten by B. caeruleus. Identification: morphological 2/5, B. caeruleus venom antigen with ELISA (3/5). No envenoming 1/5, systemic (neurotoxic) envenoming 4/5. All data below relate to the 4 patients with systemic envenoming.
• Anil et al. (2010)
  Prospective study with 72 consecutive patients; ten vials of polyvalent antivenom and three doses of 2.5 mg neostigmine at 30 min intervals after administration of 0.6 mg of atropine were administered i.v..
• Kularatne (2002)
  210 cases. Identification: In 99 (47%) situations, the offending snakes were killed and brought along with the patients and identified as common krait by the author. In the other instances other diagnostic criteria were adopted.
  
  Signs & symptoms
  Local effects
  8/88 mild local swelling (Ariaratnam et al. 2008).
  Mild pain or itching at the site of the bite 3/4 (Theakston et al. 1990).
  Swelling at the site of the bite 0/4, bite marks barely visible or not at all (Theakston et al. 1990b).
  Painful regional lymph nodes 2/4 (Theakston et al. 1990).
  Neurological effects
  Respiratory failure (paralysis of the respiratory musculature) 1/4 (Theakston et al. 1990).
  Progressive signs of paralysis with respiratory failure 2/2 (Ahuja and Singh 1954).
  Respiratory paralysis 56/88 (Ariaratnam et al. 2008).
  Typical signs and symptoms of neurotoxicity including respiratory failure (Kularatne 2002).
  8/33 mild neurotoxicity with ptosis, 17/33 severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness (Silva et al. 2016).
  Preparalytic phase 1–7 h 4/4 (Theakston et al. 1990).
  Ptosis 1.5 h after the bite 4/4 (Theakston et al. 1990).
  Bilateral external ophthalmoplegia 1.5 h after the bite 3/4 (Theakston et al. 1990).
  Autonomic neurotoxicity
  Abdominal pain 80/88 (Ariaratnam et al. 2008).
  Abdominal pain (Fernando and Dias 1982, Sethi and Rastogi 1981, Theakston et al. 1990).
  Abdominal pain cardinal symptom developing within hours of the bite. Transient hypertension, tachycardia, lacrimation, sweating, and salivation 139 patients with moderate to severe envenoming. Paralytic Ileus in 42 patients (Kularatne 2002).
  (Warrell and Williams 2023).
  Muscular effects
  Intense, prolonged muscular pain that reached a maximum on the 2nd day in hospital, with tenderness in the musculature of the extremities and trunk as well as the masseter (2/4) (Theakston et al. 1990; Discussion in Faiz et al. 2010).
  Myalgia (Kularatne 2002).
  Generalized myalgia 7/17 of patients with severe neurotoxicity; generalized muscle tenderness 7/17 of patients with severe neurotoxicity (Silva et al. 2016).
  
  Laboratory investigations (selected problems)
  Plasma myoglobin
  The plasma myoglobin concentration was raised in one of the two patients. Presynaptically, active (β) phospholipase A₂ bungarotoxin as the cause of generalized rhabdomyolysis? (Theakston et al. 1990).
  
  Clinical management (selected problems) 
  Acetylcholinesterase inhibitors 
  Bungarus caeruleus
  Edrophonium was given to 2/4 patients, but with no improvement in the neurological symptoms. Differences in efficacy can be explained by the relationship between pre- and postsynaptic toxins in individual cases of envenoming or by neuromuscular blockade already being present at the time at which treatment is administered (Theakston et al. 1990).
  Prospective study with 72 consecutive patients; ten vials of polyvalent antivenom and three doses of 2.5 mg neostigmine at 30 min intervals after administration of 0.6 mg of atropine were administered i.v.. No improvement; all patients developed respiratory paralysis, requiring assisted ventilation (Anil et al. 2010).

Bungarus candidus

Eastern Thailand/Northwestern Malaysia

• Warrell et al. (1983)
  5 patients bitten by B. candidus. Identification: morphological 4/5, B. candidus venom antigen with ELISA 1/5.

Malaysia

• Laothong et al. (2001)
  3 cases. Identification: “In all cases the snakes were seen and identified as the Malayan krait.”

Southern Vietnam

• Trinh et al. (2010)
  42 patients bitten by B. candidus. Identifiation: morphological 42/42.
  Systemic envenoming 42/42.
  
  Signs & symptoms
  Local effects
  Mild pain at the site of the bite 1/3 (Warrell et al. 1983).
  Swelling at the site of the bite 0/3 (Warrell et al. 1983).
  Fang marks visible 42/42. Local numbness 15/42 (Trinh et al. 2010).
  Neurological effects
  Preparalytic phase 75 min–3 h (3/3), but can last up to 12 h (Warrell et al. 1983).
  Ptosis 3/3, ophthalmoplegia 2/3, ophthalmoplegia not confirmed or not tested 1/3, paralysis of the masticatory musculature, glossopharyngeal and respiratory paralysis 2/3, tetraparesis 2/3, tetraparesis not confirmed or not tested 1/3 (Warrell et al. 1983).
  Ptosis 42/42, limb weakness 42/42, breathlessness 42/42, dysphonis 38/42, dyphagia 36/42, numbness of lips 23/42 (Trinh et al. 2010).
  Autonomic neurotoxicity
  Parasympathetic findings 1/3, not confirmed or not tested 2/3: dilated, fixed pupils (reduced constrictive effect of pilocarpine), heart rate consistently >120/min during the paralytic phase, no reduction in blood pressure or heart rate with a change in position or carotid sinus massage (indicates the cholinergic blocking effect of krait venom) (Warrell et al. 1983).
  Decreased parasympathetic activities 3/3 (Laothong et al. 2001)
  Dilated pupils 42/42, hypersalivation 39/42 (Trinh et al. 2010).
  Warrell and Williams (2023).
  Muscular effects
  Tenderness of the musculature and muscle pain with passive movement; however, generalized rhabdomyolysis was excluded by means of laboratory tests (Warrell et al. 1983; Discussion in Faiz et a.l 2010).
  Other signs & symptoms
  Shock 13/42 (hypotension may be linked to hyponatraemia and the possibility of venom natriuretic peptide activity) (Trinh et al. 2010).
  
  Laboratory  investigations (selected problems)
  Serum creatine kinase
  Above normal 30/42, peak levels 1375 ± 140 u/l, interpreted assuggestive of mild rhabdomyolysis in the absence of muscle trauma such as intramuscular injections (Trinh et al. 2010).
  
  Clinical management (selected problems) 
  Acetylcholinesterase inhibitors 
  Achieved marked and lasting improvement in 1/3 patients, i.e. neither the parasympathetic cholinergic nerve endings nor the motor end plates were completely blocked. This treatment was ineffective in 1/3 patients and not administered in 1/3 (Warrell et al. 1983).

Bungarus ceylonicus

Sri Lanka

• De Silva et al. (1993)
  1 case; morphological identification; review of the literature.
• Dalugama and Gawarammana(2017)
  1 case; morphological identification. Follow up of the patient in Kularatne et al (2019).
• Karalliedde and Sanmuganathan(1988)
  1 case
• Namal Kathnayaka et al. (2017)
  2 cases (1/2 ‚dry‘ bite); morphological identification.
• Namal Rathnayaka (2021)
  5 cases; identification: morphological (2/5).
• Kularatne et al. (2019) 
  2 cases (2^nd case fully reported by Dalugama and Gawarammana 2017); morphological identification.
• Rathnayaka et al. (2021)
  2 cases; morphological identification.
  
  Signs & symptoms
  Local effects
  No local reaction (Dalugama et al. 2017).
  Local pain and numbness (Kularatne et al. 2019).
  Neurological effects
  Bilateral partial ptosis, ophthalmoplegia, facial muscle weakness, dysphagia, weak neck muscle power (Dalugama et al. 2017).
  Ptosis, opthalmoplegia, facial muscle weakness, dysphagia, complete paralysis lower limbs, nearly complete – with the exception of fingers – upper limbs. Boken neck syndrome (Kularatne et al. 2019).
  Paralysis of the respiratory musculature and respiratory failure 6 h after the bite.  Dysphagia preceded these symptoms by a number of hours (Karalliedde and Sanmuganathan 1988).
  Progressive paralysis with respiratory failure commenced within an hour after the bite (de Silva et al. 1993).
  Autonomic neurotoxicity
  Colicky abdominal pain (Dalugama et al. 2017).
  Abdominal pain (Kularatne et al. 2019).
  (Warrell and Williams 2023)
  Muscular effects
  Muscular pain (Kularatne et al. 2019).
  
  Laboratory  investigations (selected problems)
  Serum creatine kinase
  Max. 1454 U/L on day 4 (26-174 U/L) 1/1 (Kularatne et al. 2019)
  
  Clinical management (selected problems) 
  Acetylcholinesterase inhibitors 
  Edrophonium had no apparent effect (de Silva et al. 1993; Karalliedde and Sanmuganathan 1988).

Bungarus fasciatus

Thailand

• Viravan et al. (1992)
  1 case; identification: ELISA

 Myanmar

• Pe et al. (1997)
  1 case; identification: dead snake.
  
  Signs & symptoms
  Local effects
  Mild swelling (Pe et al. 1997)
  Local pain and swelling (Viravan et al. 1986).
  Neurological effects
  Ptosis, paralysis of the respiratory musculature with respiratory failure (Pe at al. 1997; Viravan et al. 1986).
  Muscular effects
  ?

Bungarus multicinctus

Taiwan

• Mao et al. (2017)
  Retrospective hospital-based study.  44 B. multicinctus bites are described. 9 were asymptomatic. Identification:“Definite case“ (6/44):morphological,“suspected case” (27/44): patient recognized snake on pictures shown, „clinical case“(11/44):typical manifestation as determined through physical examination, serial wound inspection, and a relevant history. 9/44 asymptomatic.
• Mao et al. (2024)
  1 case

Vietnam

• Hung et al. (2009)
  60 ICU-treated patients bitten by B. multicinctus. Identification: morphological; by patient; circumstances and clinical features; B. multicinctus only krait of medical relevance in the region.

Captive snake

• Höjer et al. (2010)
  
  Signs & symptoms
  Local effects
  0/60(Hung et al. 2009).
  Numbness (13/35)(Mao et al. 2017).
  Minimal (Mao et al. 2024).
  Neurological effects
  Typical neurotoxic signs and symptoms. Ptosis 56/60, respiratory muscles (dyspnoea) 52/60 (Hung et al. 2009).
  The envenomed patients had typical neurotoxic signs and symptoms. Motor effects 33/35, respiratory failure 12/33 (Mao et al. 2017).
  Autonomic neurotoxicity
  Abdominal pain (11/44) (Mao et al. 2017).
  (Warrell and Williams 2023).
  Muscular effects
  Generalized myalgia 41/60 (Hung et al. 2009; Discussion in Faiz et al. 2010).
  
  Laboratory investigations (selected problem)
  Hyponatremia
  Severe hyponatraemia (dropping to 104 mmol/l within 48h) 1/1 (Höjer et al. 2010)
  Hyponatraemia 25/60 (Hung et al. 2009).
  3/44 Sodium ≤ 135 mE/L (125, 128, 134 mE/L) (Mao et al. 2017)
  Serum creatine kinase
  1/44 CK ≥1000 U/L (Mao et al. 2017)

Bungarus niger

Bangladesh

• Faiz et al. (2010) 
  5 cases; identification: morphological.

Nepal

• Pandey et al. (2016)
  1 case ; identification : morphological.
  
  Signs & symptoms
  Local effects
  Burning pain; no swelling(Pandey et al. 2016).
  Pain (Faiz et al. 2010).
  Neurological effects
  Severe neurotoxic signs and symptoms 5/5 (Faiz et al. 2010).
  Bilateral ptosis, slurred speech; muscular paralysis, respiratory failure (Pandey et al. 2016).
  Autonomic neurotoxicity
  Severe abdominal pain, frequent vomiting (Pandey et al. 2016)
  Muscular effects
  Severe generalized myalgia and odynophagia 1/5 (Faiz et al 2010).
  
  Laboratory investigations (selected problems)
  Serum creatine kinase
  Peak serum creatine kinase 29 960 u/l with myoglobulinuria (rhabdomyolysis) and acute renal failure 1/5; modest increase of serum creatine kinase 1/5 (Faiz et al 2010).

Bungarus sindanus

India (Maharastra)

• Pillai et al. (2012)
  1 case; identification: morphological.
  
  Signs & symptoms
  Local effects
  No swelling or inflammation (Pillai et al. 2012).
  Neurological effects
  Progressive neuromuscular paralysis and respiratory failure (Pillai et al. 2012).
  Autonomic neurotoxicity 
  Abdominal pain and autonomic disturbances complicated by four prolonged episodes of pulseless ventricular tachycardia requiring defibrillation (see also ‘Cardiac effects’ below) (Pillai et al. 2012).
  (Warrell and Williams 2023).
  Muscular effects
  No clinical evidence reported (Pillai et al. 2012).
  ? Cardiac effects
  Four prolonged episodes of pulseless ventricular tachycardia requiring defibrillation (see also ‘Autonomic neurotoxicity? above), and followed by pulmonary edema secondary to impaired left ventricular systolic function (see ‘ECG’ below) (Pillai et al. 2012).
  
  Laboratory and physical investigations (selected problems)
  Serum creatine kinase
  Slightly elevated levels of creatine kinase (CK-MB 34 U/L, CK-NAC 181 U/L assayed 6 hr before the pulseless ventricular tachycardia (9 hr after the bite; pre-defibrillation) (Pillai et al .2012).
  ECG
  Persistent ST depression and T wave inversion and general myocardial damage in echocardiography are interpreted as venom induced toxic myocarditis (Pillai et al. 2012).
  
  Clinical management (selected problems) 
  Acetylcholinesterase inhibitors 
  No effect (Pillai et al. 2012).

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• Trinh KX, Khac QL, Trinh LX, Warrell DA. Hyponatraemia, rhabdomyolysis, alterations in blood pressure and persistent mydriasis in patients envenomed by Malayan kraits (Bungarus candidus) in southern Viet Nam. Toxicon. 2010 Nov;56(6):1070-5. PMID: 20637219 https://doi.org/10.1016/j.toxicon.2010.06.026
• Viravan C, Veeravat U, Warrell MJ, Theakston RD, Warrell DA. ELISA confirmation of acute and past envenoming by the monocellate Thai cobra (Naja kaouthia). Am J Trop Med Hyg. 1986 Jan;35(1):173-81. PMID: 3946735. https://doi.org/10.4269/ajtmh.1986.35.1
• Warrell DA, Williams DJ. Clinical aspects of snakebite envenoming and its treatment in low-resource settings. Lancet. 2023 Apr 22;401(10385):1382-1398. PMID: 36931290. https://doi.org/10.1016/s0140-6736(23)00002-8
• Warrell DA, Looareesuwan S, White NJ, Theakston RD, Warrell MJ, Kosakarn W, Reid HA. Severe neurotoxic envenoming by the Malayan krait Bungarus candidus (Linnaeus): response to antivenom and anticholinesterase. Br Med J (Clin Res Ed). 1983 Feb 26;286(6366):678-80. PMID: 6402200; PMCID: PMC1547089. https://doi.org/10.1136/bmj.286.6366.678