Clinic: Daboia russelii and Daboia siamensis

Examine for venom effects

Autopharmacological effects

• Nausea, vomiting
• Sweating
• Urticaria, angiooedema
• Arterial hypotension / hypovolaemic shock (transient, recurrent; immediate; delayed (CLS))
• Diarrhoea
• Bronchospasm 

Local Effects

• Pain
• Tender local (spreading) swelling
• Blistering
• Lymphangiopathy and lymphadenopathy
• Necrotic skin

Haematological effects 

• Clotting disturbances:
  • Bleeding from the fang marks and from injuries, in particular ones that are not located in the region in which venom application occurred.
  • Bleeding into the skin (ecchymosis, petechiae)
  • Gingival bleeding, bleeding from the nose, conjunctiva, haematemeis, bleeding per rectum, including melaena, haematuria, haemoptysis.
  • Oliguria, anuria (VICC / AKI)
• Bleeding and/or haemolytic anaemia:
  • Arterial hypotension (haemorrhagic shock)
  • Acute abdomen (intra-abdominal bleeding!)
  • Loin pain/renal bed sensitive to percussion (ischaemia, renal haemorrhage!)
  • Local neurological signs, meningism, coma (intracranial bleeding!)
  • Pale sclera (bleeding, haemolysis!)
  • Oliguria, anuria (arterial hypotension / AKI!)
  • Neurological features of hypoglycaemia, or refractory shock (acute pituitary-adrenal insufficiency!)  (bleeding!)

Neurological effects

• Descending flaccid paralysis (rarely progresses to involve bulbar and respiratory muscles):
  • 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.  

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. 

Renal effects

• Acute kidney injury:
  • Loin pain (lower back pain)
  • Renal bed sensitive to percussion
  • Haematuria, haemoglobinuria, myoglobinuria
  • Oliguria (< 400 ml of urine / 24 h), anuria
  • Uraemia (nausea, acidotic breathing, hiccups, pleuritic chest pain, encephalopathy) 

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.

 ¹ “Acute profound hypotension with or without other features of anaphylaxis is part of the autopharmacological syndrome which may occur within minutes of bites by Daboia species. It may be caused by release of endogenous vasoactive compounds such as nitric oxide, kinins, histamine, serotonin and endothelins.” (Warrell 2023)

²Capillary leak syndrome (CLS)

“CLS includes chemosis, periorbital, and facial oedema with distinctive bilateral parotid swellings giving the patient a so-called viper’s head appearance, as well as pleural effusions, ascites, macular oedema, acute angle-closure glaucoma, haemoconcentration, proteinuria, and hypovolaemic shock with low central venous pressure. Patients with CLS are unresponsive to antivenom and are at increased risk of acute kidney injury and death. Symptoms usually appear 12–48 h after the bite, accompanied by intense thirst. These features were first reported in Burma from envenoming by D. siamensis and in India from D. russelii.” (Warrell and Williams 2023).

“In people who are bitten by a Russell’s viper, the generalised increase in capillary permeability underlying CLS might be due to svVEGF (ie, VR-1)” (Warrell and Williams 2023).

Frequently recognized in Southern parts of India, especially Kerala. Pathogenesis of CLS is not fully elucidated: Increased capillary permeability is cytokine activation by the venom? Vascular apoptosis‑inducing proteins in venom leading to endothelial cell death? (Udayabhaskaran et al. 2017).

³can be mild or absent (Warrell 1989).

⁴Acute and chronic hypopituitarism and diabetes insipidus, “perhaps through deposition of fibrin microthrombi and haemorrhage in the pituitary gland resulting from the action of venom procoagulant enzymes and haemorrhagins”(Anatonypillai et al. 2011).

⁵Venom-induced consumptive coagulopathy (VICC)

⁶Warrell and Williams (2023)

⁷Mild neuromuscular dysfunction with no long-term effects. “In previous studies conducted in Sri Lanka, neuromuscular dysfunction due to Russell’s viper envenoming has resulted in bulbar, neck, and respiratory muscle paralysis, whereas the present study reports none. The reason for this may be that patients in our study reached the hospital and received antivenom earlier. “(Silva et al. 2016a).

⁸South India

⁹Mild and non-life threatening, as evident from the low frequency of generalized myotoxicity and low concentrations of serum creatine kinase in envenomed patients. There is a small possibility that myotoxicity may occur in patients with severe envenoming in which antivenom is delayed (Silva et al. 2016b).

¹⁰Possible South India

¹¹Mostly mild

¹²Severe acute kidney injury: “There has also been an apparent reduction in the incidence of severe acute kidney injury over the last three decades. Thus, earlier treatment may be leading to a change in the clinical profile of envenoming, with it becoming less lethal than reported in historical studies.”(Silva et al. 2016a).

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
Necroses: debridement; split-thickness skin grafting
Systemic antibiotics: standard indications
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 daboia sp. - specific features

see 

• 'Species-specific envenoming pattern' above

and

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

Key issues:

Early hypotensive collapse and shock - autopharmacological, (anaphylactic)

“Acute profound hypotension with or without other features of anaphylaxis is part of the autopharmacological syndrome which may occur within minutes of bites by Daboia species. It may be caused by release of endogenous vasoactive compounds such as nitric oxide, kinins, histamine, serotonin and endothelins.” (Warrell 2023) 

Capillary leak syndrome (CLS)

“A unique complication that follows Russell's viper envenomation. This syndrome has a very high fatality rate and is characterized by parotid swelling, chemosis, periorbital edema, hypotension, albuminuria, hypoalbuminemia, and haemoconcentration. This syndrome is frequently recognized from the southern parts of India, especially from the state of Kerala. It has been postulated that a vascular apoptosis inducing component of Russell's viper venom that is not neutralized by the commercially available anti-snake venom (ASV) is responsible for this complication as it occurs even after adequate doses of ASV administration in most cases. Acute kidney injury often requiring dialysis is invariably present in all patients because of reduced renal perfusion and ischemic acute tubular necrosis as a result of hypotension. Management mainly involves aggressive fluid resuscitation to maintain adequate tissue perfusion.” (Udayabhaskaran et al. 2017).
See also Warrell and Williams (2023).

Respiratory failure

Lifesaving in neurotoxic Russel’s viper envenoming (as supportive treatment and when antivenoms are not available or fail):

Airway management
Breathing: Oxygen ⇨ assisted ventilation ⇨ mechanical ventilation

Thrombotic microangiopathy (TMA)

“TMA include disseminated intravascular coagulation, microangiopathic haemolytic anaemia diagnosed by finding schistocytes in peripheral blood films, thrombocytopenia, and acute kidney injury associated with arteriolar and capillary microthrombi. TMA with acute kidney injury is increasingly recognised in patients envenomed by Russell’s vipers and a variety of other species.” (Warrell and Williams 2023).
See also Noutsos et al. (2020, 2022).

Venom-induced consumptive coagulopathy (VICC)

Gingival bleeding, epistaxis, haematemesis, haematuria, etc., haemorrhagic schock. Most likely bleeding and deposition of fibrin microthrombi in the anterior hypophysis:

Acute and chronic pituitary or adrenal insufficiency and diabetes insipidus

Russell’s viper envenoming – geographical variation of clinical manifestations across SE Asia (Warrell 1989)
Hypopituitarism following Daboia siamensis and D. russelii envenoming (Antonypillai et al. 2011)
Pathophysiology 
Most likely bleeding and deposition of fibrin microthrombi in the anterior hypophysis (Anatonypillai et al. 2011).
Acute signs
Severe headache, shock, signs of hypoglycaemia and loss of consciousness, onset 21 h–9 days after the bite (Anatonypillai et al. 2011). 
Chronic signs
Hoarse voice, low drive, reduced libido, oligo/amenorrhoea, impotence, absence of pubic hair, hyperpigmentation, signs of hypothyroidism, Addisonian crisis possible, diabetes insipidus (Anatonypillai et al. 2011).
Delayed hypopituitarism (Shivaprasad et al. 2019).
Pituitary dysfunction in survivors (Naik et al. 2018).
Clinical Management
Acute
“In Burma acute pituitary or adrenal insufficiency is frequent enough to justify routine use of intravenous hydrocortisone in all cases of D. siamensis-related shock.” (Warrell and Williams 2023)
See also Antonypillai et al. (2011), Warrell (1989).
Chronic
If patient develops polyuria, particularly after the introduction of steroids: Investigate for diabetes insipidus. Follow-up: for at least 6 months regarding hypopituitarism. Chronic ill health in survivors of the acute episode: Consider the possibility of hypopituitarism (Antonypillai et al. 2011).
Predictors of hypopituitarism (Bhat et al. 2019).

Endocrine and Metabolic Manifestations
Bhattacharya et al. (2020).

Acute kidney injury (AKI), chronic kidney disease

“Envenoming by many snake species occasionally results in acute kidney injury, but Russell’s vipers are the most dangerous. Acute kidney injury is the major cause of mortality and morbidity among people who have been bitten by these species. Direct venom nephrotoxicity, renal ischaemia secondary to shock, disseminated intravascular coagulation with thrombotic microangiopathy (TMA), haemoglobinuria, myoglobinuria, and hyperkalaemia contribute to acute tubular necrosis.” (Warrell and Williams 2023)
“The risk of progression from acute kidney injury to chronic kidney disease has been seriously underestimated because of inadequate follow-up. However, in India (e.g., Tamil Nadu and Kolkata) and Sri Lanka, where most cases were attributable to D russelii, progression from acute kidney injury to chronic kidney disease after 1–3 years, often with associated hypertension, ranged from 26% to 49%.” (Warrell and Williams 2023)

Specific treatment (antivenoms)

• WHO Snakebite Information and Data Platform

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

References

• Antonypillai CN, Wass JA, Warrell DA, Rajaratnam HN. Hypopituitarism following envenoming by Russell's vipers (Daboia siamensis and D. russelii) resembling Sheehan's syndrome: first case report from Sri Lanka, a review of the literature and recommendations for endocrine management. QJM. 2011 Feb;104(2):97-108. PMID: 21115460. https://doi.org/10.1093/qjmed/hcq214
• Bhat S, Mukhopadhyay P, Raychaudhury A, Chowdhury S, Ghosh S. Predictors of hypopituitarism due to vasculotoxic snake bite with acute kidney injury. Pituitary. 2019 Dec;22(6):594-600. PMID: 31556012. https://doi.org/10.1007/s11102-019-00990-8
• Bhattacharya S, Krishnamurthy A, Gopalakrishnan M, Kalra S, Kantroo V, Aggarwal S, Surana V. Endocrine and Metabolic Manifestations of Snakebite Envenoming. Am J Trop Med Hyg. 2020 Oct;103(4):1388-1396. PMID: 32602439; PMCID: PMC7543852.
• Naik BN, Bhalla A, Sharma N, Mokta J, Singh S, Gupta P, Rai A, Subbiah S, Bhansali A, Dutta P. Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A prospective study. Neurol India. 2018 Sep-Oct;66(5):1351-1358. PMID: 30233002. https://doi.org/10.4103/0028-3886.241378
• Noutsos T, Currie BJ, Lek RA, Isbister GK. Snakebite associated thrombotic microangiopathy: a systematic review of clinical features, outcomes, and evidence for interventions including plasmapheresis. PLoS Negl Trop Dis. 2020 Dec 8;14(12):e0008936. PMID: 33290400; PMCID: PMC7748274. https://doi.org/10.1371/journal.pntd.0008936
• Noutsos T, Currie BJ, Wijewickrama ES, Isbister GK. Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice. Toxins (Basel). 2022 Jan 14;14(1):57. PMID: 35051033; PMCID: PMC8778654. https://doi.org/10.3390/toxins14010057
• Shivaprasad C, Aiswarya Y, Sridevi A, Anupam B, Amit G, Rakesh B, Annie PA, Anish K. Delayed hypopituitarism following Russell's viper envenomation: a case series and literature review. Pituitary. 2019 Feb;22(1):4-12. PMID: 30317419. https://doi.org/10.1007/s11102-018-0915-1
• Silva A, Maduwage K, Sedgwick M, Pilapitiya S, Weerawansa P, Dahanayaka NJ, Buckley NA, Siribaddana S, Isbister GK. Neurotoxicity in Russell's viper (Daboia russelii) envenoming in Sri Lanka: a clinical and neurophysiological study. Clin Toxicol (Phila). 2016a Jun;54(5):411-9. PMID: 26923566. https://doi.org/10.3109/15563650.2016.1143556
• Silva A, Johnston C, Kuruppu S, Kneisz D, Maduwage K, Kleifeld O, Smith AI, Siribaddana S, Buckley NA, Hodgson WC, Isbister GK. Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming. PLoS Negl Trop Dis. 2016b Dec 2;10(12):e0005172. PMID: 27911900; PMCID: PMC5135039. https://doi.org/10.1371/journal.pntd.0005172
• Udayabhaskaran V, Arun Thomas ET, Shaji B. Capillary Leak Syndrome Following Snakebite Envenomation. Indian J Crit Care Med. 2017 Oct;21(10):698-702. PMID: 29142382; PMCID: PMC5672676. https://doi.org/10.4103/ijccm.IJCCM_41_17
• 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. Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites. Trans R Soc Trop Med Hyg. 1989 Nov-Dec;83(6):732-40. PMID: 2533418. https://doi.org/10.1016/0035-9203(89)90311-8
• 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

Daboia russelii (West of Bay of Bengal)

Described as: Daboia russelii pulchella

Sri Lanka

Case reports and case series

• Antonypillai et al. (2011)
  1 case
• Herath et al. (2012)
  15 cases (2 renal biopsies). Identification: by the doctors at the original referring hospitals by examining the dead specimens.
• Jeyarajah (1984)
  22 V. r. pulchella bites; identification: description of the snake by patients and recognition from photographs.
• Phillips et al. (1988)
  36 Vipera russelli pulchella bites (= Daboia russelli pulchella); identification: morphological or immunological with ELISA according to the methods described by Theakston et al. 1977 and Ho et al. 1986a.

Prospective cohort studies

• Silva et al. (2016a) – Neurological effects
  245 cases; identification: morphological and / or enzyme immunoassay. Presented within a median 2.5 h (interquartile range: 1.75–4.0 h) post-bite.
• Silva et al. (2016b) – Muscular effects
  245 cases; identification: morphological and / or enzyme immunoassay. Presented within a median 2.5 h (interquartile range: 1.75–4.0 h) post-bite.

Reviews

• Warrell (1989)
  Russell’s viper envenoming – geographical variation of clinical manifestations across SE Asia

Signs & symptoms 
Local effect
Swelling 16/22 (mostly grade 2; mean increase in the circumference of the affected extremity 6.4 cm ± 5.4%). Pain 21/22 (usually commencing within seconds or minutes, but also later; 2 patients with clear systemic signs of envenoming had no pain!). Blistering 2/22, 1 of these patients had subsequent necrosis (Phillips et al. 1988).
Local effects in 244/245 patients; none developed local tissue necrosis or gangrene (Silva et al. 2016a).
Haematological effects
Bleeding
Persistent bleeding from bite marks 2/22, discoid-shaped haemorrhages 1/22; gingival bleeding 1/11, haematemesis 4/22; epistaxis 1/22; haematuria 1/22; subarachnoid haemorrhage 1/22, intracerebral haemorrhage 1/22 (Phillips et al. 1988).
Bleeding manifestations in 82 (50%) of 166/245 (68%) with coagulopathy (Silva et al. 2016a).
Due to bleeding:
Acute and chronic hypopituitarism and diabetes insipidus
Chronic hypopituitarism
1 Patient diagnosed chronic hypopituitarism (clinical: generalized weakness, lethargy, sleepiness and reduced libido, pituitary function tests: deficiencies in steroids, thyroid and gonadal axes) following presumed Daboia russelli pulchella bite years earlier (Antonypillai et al. 2011)
Thrombotic microangiopathy (TMA)
“TMA include disseminated intravascular coagulation, microangiopathic haemolytic anaemia diagnosed by finding schistocytes in peripheral blood films, thrombocytopenia, and acute kidney injury associated with arteriolar and capillary microthrombi. TMA with acute kidney injury is increasingly recognised in patients envenomed by Russell’s vipers and a variety of other species.” (Noutsos et al. 2020, 2022, Warrell and Williams 2023).
Neurological effects
Blurred vision/double images 18/22. External ophthalmoplegia: complete 10/22, incomplete 8/22. Ptosis: complete 4/22, partial 13/22. Dysphagia 11/22, inability to open the mouth fully 5/22. No patient developed generalised muscle paralysis or respiratory failure as a consequence of paralysis of the respiratory musculature (Phillips et al. 1988).
Neurological effects in 130 / 245 (53%); Ptosis (100%), blurred vision (93%), and ophthalmoplegia (90%) with weak extraocular movements, strabismus, and diplopia. Neurotoxicity developed within 8 h post-bite in all patients. No bulbar, respiratory or limb muscle weakness. Antivenom immediately decreased unbound venom in blood. Of 52 patients without neurotoxicity when they received antivenom, 31 developed neurotoxicity.
Day 3 after envenoming: Neurological features resolved in 80% of patients; ptosis and weak eye movements resolved last.
Week 6 or month 6: No residual clinical or neurophysiological abnormalities (Silva et al. 2016a).
Muscular effects
Generalised muscular pain in 6/22, generalised pain on palpation of the muscles 7/22, black urine 6/22, 2 of these patients were oliguric (Phillips et al. 1988).
Local myalgia in 177/245 (72.2%); local muscle tenderness 173/245 (70.6%); generalized myalgia and muscle tenderness 35/245 (14.2%) and 29 (11.8%), respectively (Silva et al. 2016b).
Renal effects
Oliguria 2/22 (Phillips et al. 1988).
Oliguria 19/22, 4 of these patients died (Jeyarajah 1984).
Oliguria 19 / 245 (8%) Urine output < 400 ml/24 h in 19 (8%) patients of which five developed anuria for 24 h requiring haemodialysis (Silva et al. 2016a).
“The risk of progression from acute kidney injury to chronic kidney disease has been seriously underestimated because of inadequate follow-up. However, in India (e.g., Tamil Nadu and Kolkata) and Sri Lanka, where most cases were attributable to D. russelii, progression from acute kidney injury to chronic kidney disease after 1–3 years, often with associated hypertension, ranged from 26% to 49%.” (Warrell and Williams 2023)

Laboratory investigations 
Sri Lanka
Case series 
Haemostasis

• Phillips et al. (1988)
  19 patients underwent thorough investigations: 10/19 had moderate to severe defibrinogenation.
• Silva et al. (2016a,b)
  Coagulopathy in 166/245 (68%) with bleeding manifestations in 82 (50%). 

Type of haemostatic defect
Venom-induced consumption coagulopathy (VICC) 
Myoglobin 
In plasma (100–8,000 ng/ml) 19/19, myoglobinuria (110–16,000 ng/ml) 14/18 (rhabdomyolysis) (Phillips et al. 1988).
Serum creatine kinase
Serum creatine kinase (CK) >300 U/l in 37/245 in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049) (Silvia et al. 2016b).
ELISA
At the initial investigation, specific venom antigen was found in the serum of 23/23 patients with systemic envenoming. ELISA is important in Sri Lanka as it is not possible to clinically distinguish elapid (cobra, krait) and Vipera russelli pulchella bites (= Daboia russelli pulchella) without additional information. It may occur that after a Vipera russelli pulchella bite (= Daboia russelli pulchella) neurological signs and symptoms appear before the haemostatic defect is detectable on the clotting time test. As V. russelli pulchella venom contains relatively weak activators of clotting factors (V, X), clotting time has low sensitivity for the detection of this haemostatic defect (Phillips et al. 1988).

Clinical management 
Arterial hypotension
Bleeding affecting blood pressure is not as commonly observed as in Myanmar (described as: D. r. siamansis); increased capillary permeability as the cause of arterial hypotension also appears to be less common than in Myanmar (Phillips et al. 1988).
Renal failure
Patient characterisation: 2/22 developed oliguric acute renal failure, both had myoglobinuria (Phillips et al. 1988). Treatment: peritoneal dialysis 2/2, successful (Phillips et al. 1988).
Acute and chronic hypopituitarism
1 case and review of the literature (Antonypillai et al. 2011).
Respiratory failure
Patient characterisation: 0/22 developed envenoming-induced paralysis of the respiratory musculature that represented an indication for artificial respiration (Phillips et al. 1988). Treatment: if necessary, artificial respiration. Edrophonium (Tensilon) 10 mg i.v.: without success 9/9 (Phillips et al. 1988). 

References

• Antonypillai CN, Wass JA, Warrell DA, Rajaratnam HN. Hypopituitarism following envenoming by Russell's vipers (Daboia siamensis and D. russelii) resembling Sheehan's syndrome: first case report from Sri Lanka, a review of the literature and recommendations for endocrine management. QJM. 2011 Feb;104(2):97-108. PMID: 21115460. https://doi.org/10.1093/qjmed/hcq214
• Bhattacharya S, Krishnamurthy A, Gopalakrishnan M, Kalra S, Kantroo V, Aggarwal S, Surana V. Endocrine and Metabolic Manifestations of Snakebite Envenoming. Am J Trop Med Hyg. 2020 Oct;103(4):1388-1396. PMID: 32602439; PMCID: PMC7543852. https://doi.org/10.4269/ajtmh.20-0161
• Herath HM, Wazil AW, Abeysekara DT, Jeewani ND, Weerakoon KG, Ratnatunga NV, Bandara EH, Kularatne SA. Chronic kidney disease in snake envenomed patients with acute kidney injury in Sri Lanka: a descriptive study. Postgrad Med J. 2012 Mar;88(1037):138-42. Epub 2012 Jan 25. PMID: 22282736. https://doi.org/10.1136/postgradmedj-2011-130225
• Jeyarajah R. Russell's viper bite in Sri Lanka. A study of 22 cases. Am J Trop Med Hyg. 1984 May;33(3):506-10. PMID: 6731682. https://doi.org/10.4269/ajtmh.1984.33.506
• Noutsos T, Currie BJ, Lek RA, Isbister GK. Snakebite associated thrombotic microangiopathy: a systematic review of clinical features, outcomes, and evidence for interventions including plasmapheresis. PLoS Negl Trop Dis. 2020 Dec 8;14(12):e0008936. PMID: 33290400; PMCID: PMC7748274. https://doi.org/10.1371/journal.pntd.0008936
• Noutsos T, Currie BJ, Wijewickrama ES, Isbister GK. Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice. Toxins (Basel). 2022 Jan 14;14(1):57. PMID: 35051033; PMCID: PMC8778654. https://doi.org/10.3390/toxins14010057
• Phillips RE, Theakston RD, Warrell DA, Galigedara Y, Abeysekera DT, Dissanayaka P, Hutton RA, Aloysius DJ. Paralysis, rhabdomyolysis and haemolysis caused by bites of Russell's viper (Vipera russelli pulchella) in Sri Lanka: failure of Indian (Haffkine) antivenom. Q J Med. 1988 Sep;68(257):691-715. PMID: 3256900.
• Ramachandran S, Ganaikabahu B, Pushparajan K, De Silva CK, Wijesekera J. Myonecrosis due to Russell's viper bites in Sri Lanka. Am J Trop Med Hyg. 1994 May;50(5):597-601. PMID: 8203709. https://doi.org/10.4269/ajtmh.1994.50.597   
• Ratcliffe PJ, Pukrittayakamee S, Ledingham JG, Warrell DA. Direct nephrotoxicity of Russell's viper venom demonstrated in the isolated perfused rat kidney. Am J Trop Med Hyg. 1989 Mar;40(3):312-9. PMID: 2929855. https://doi.org/10.4269/ajtmh.1989.40.312
• Silva A, Maduwage K, Sedgwick M, Pilapitiya S, Weerawansa P, Dahanayaka NJ, Buckley NA, Siribaddana S, Isbister GK. Neurotoxicity in Russell's viper (Daboia russelii) envenoming in Sri Lanka: a clinical and neurophysiological study. Clin Toxicol (Phila). 2016a Jun;54(5):411-9. PMID: 26923566. https://doi.org/10.3109/15563650.2016.1143556
• Silva A, Johnston C, Kuruppu S, Kneisz D, Maduwage K, Kleifeld O, Smith AI, Siribaddana S, Buckley NA, Hodgson WC, Isbister GK. Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming. PLoS Negl Trop Dis. 2016b Dec 2;10(12):e0005172. PMID: 27911900; PMCID: PMC5135039 https://doi.org/10.1371/journal.pntd.0005172
• Warrell DA. Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites. Trans R Soc Trop Med Hyg. 1989 Nov-Dec;83(6):732-40. PMID: 2533418. https://doi.org/10.1016/0035-9203(89)90311-8
• 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

Described as: Daboia russelii russelii 

North India

Case reports and case series 

• Ahuja and Singh (1954)
  1 case; identification: morphological.

Northwest India

Case reports and case series 

• Chugh et al. (1975)
  8 cases with acute renal failure; identification: snake killed and then identified 2/8, description by the patient or witnesses to the accident 5/8, unidentified 1/8; the investigators found that the clinical picture corresponded to that of a Vipera russelli russelli bite (= Daboia russelii russelii) in all cases.

South India

Case reports and case series 

• Eapen et al. (1976)
  3 cases; snakes not identified; in analogy to investigations from Myanmar, V.  russelli most probably the cause.
• Matthai and Date (1981)
  42 cases (children with acute renal failure); identification: snake killed and then identified 12/42, description by the patient or witnesses to the accident 17/42, unidentified 13/42; the investigators found that the clinical picture corresponded to that of a Vipera russelli bite (= Daboia russelii) in all cases; it is further argued that experience in India shows that all patients with acute renal failure following a snakebite who brought in the snake for identification had been bitten by V. russelli.

See also cases and case series in “Laboratory and physical investigations” below.

Reviews 

• Warrell (1989)
  Russell’s viper envenoming – geographical variation of clinical manifestations across SE Asia.

Signs & symptoms 
Autopharmacological effects
Vomiting, diarrhoea, abdominal pain (Ahuja and Singh 1954).
Local effects
Local pain and swelling 42/42. Onset more or less immediately after the bite, at the latest after 72 h, resolution within 10 days (Matthai and Date 1981).
Local stabbing pain and swelling (extending to the groin) (Ahuja and Singh 1954).
Haematological effects
Bleeding
Gingival bleeding, epistaxis, haematemesis, haematuria, haemorrhagic schock (Ahuja and Singh 1954).
Gingival bleeding 38/42, haematuria 33/42, ecchymosis 30/42, haematemesis 24/42, melaena 24/42 (bleeding commenced within 2–3 h, gingival bleeding first), icterus 8/42 (Matthai and Date 1981).
Due to bleeding:
Acute and chronic hypopituitarism and diabetes insipidus
Signs of acute (1/3) and chronic (2/3) hypopituitarism (Eapen et al. 1976).
See also “Laboratory and physical investigations” below.
Neurological effects
South India (Warrell 1989).
Muscular effects
Possible in south India (Warrell 1989).
Renal effects
Acute renal failure: anuria within 42 h after the bite (42/42), anuria within 3 h after the bite (8/42). Acute renal failure occurred more commonly in children than in adults (p < 0.001); the acute renal failure persisted for 10–25 days (Matthai and Date 1981).
“The risk of progression from acute kidney injury to chronic kidney disease has been seriously underestimated because of inadequate follow-up. However, in India (e.g., Tamil Nadu and Kolkata) and Sri Lanka, where most cases were attributable to D russelii, progression from acute kidney injury to chronic kidney disease after 1–3 years, often with associated hypertension, ranged from 26% to 49%.” (Warrell and Williams 2023)

Laboratory investigations

Haemostasis
Type of haemostatic defect
Venom-induced consumption coagulopathy (VICC). 

Endocrinology
South India (Kerala)

• Eapen et al. (1976)
  3 cases (1 patient with acute and 2 patients with chronic hypopituitarism); snakes not identified; in analogy to investigations from Myanmar, V.  russelli most probably the cause.

South India (Karnataka)

• Shivaprasad et al. (2019)
  Retrospective review of patient data and literature: presentation, manifestations, hormonal profiles, and radiological features of delayed hypopituitarism (DHP) presenting months to years after recovering from snake bites.
  8 cases; identification: based on the discharge summary of the acute episode, description of the snake, and corroboration with representative photos.
  “DHP is an important complication of RVE, and a delay in its diagnosis is associated with significant morbidity. Patients with RVE should be followed up for a long term to identify DHP.”

North India

• Bhat et al. (2019)
  51 cases; identification: mixed criteria (see ‘Patients and Methods’)
  Predictors of hypopituitarism.

Cases mainly from North India

• Naik et al. (2018)
  60 cases; identification: mixed criteria (see ‘Patients and Methods’)
  Pituitary dysfunction in survivors: Hormone profiles.

Reviews

• Warrell (1989)
  Russell’s viper envenoming – geographical variation of clinical manifestations across SE Asia
• Antonypillai et al. (2011)
  Hypopituitarism following Daboia siamensis and D. russelii envenoming 

Renal biopsy
Case series

• Date and Shastry (1981)
  Identification: description by the patient or witnesses to the accident; recognition from photographs.
  Histology: Cortical necrosis (aetiology: ischaemia due to DIC).
• Date and Shastry (1982)
  9 cases with acute renal failure; identification: description by the patient or witnesses to the accident.
  Histology: Cortical necrosis (aetiology: ischaemia due to DIC).
• Matthai and Date (1981)
  Histology: Acute tubular necrosis (aetiology: ischaemia due to DIC).

Clinical management
Predictors of hypopituitarism 
(Bhat et al. 2019)

References

• Ahuja ML and Singh G. Snake bite in India. Indian J Med Res. 1954 Oct;42(4):661-86. PMID: 13232717.

• Antonypillai CN, Wass JA, Warrell DA, Rajaratnam HN. Hypopituitarism following envenoming by Russell's vipers (Daboia siamensis and D. russelii) resembling Sheehan's syndrome: first case report from Sri Lanka, a review of the literature and recommendations for endocrine management. QJM. 2011 Feb;104(2):97-108. PMID: 21115460. https://doi.org/10.1093/qjmed/hcq214
• Bhat S, Mukhopadhyay P, Raychaudhury A, Chowdhury S, Ghosh S. Predictors of hypopituitarism due to vasculotoxic snake bite with acute kidney injury. Pituitary. 2019 Dec;22(6):594-600. PMID: 31556012. https://doi.org/10.1007/s11102-019-00990-8
• Chugh KS, Aikat BK, Sharma BK, Dash SC, Mathew MT, Das KC. Acute renal failure following snakebite. Am J Trop Med Hyg. 1975 Jul;24(4):692-7. PMID: 1155703. https://doi.org/10.4269/ajtmh.1975.24.692
• Date A, Shastry JC. Renal ultrastructure in cortical necrosis following Russell's viper envenomation. J Trop Med Hyg. 1981 Feb;84(1):3-8. PMID: 7206019.
• Date A, Shastry JC. Renal ultrastructure in acute tubular necrosis following Russell's viper envenomation. J Pathol. 1982 Jul;137(3):225-41. PMID: 7097398. https://doi.org/10.1002/path.1711370307
• Eapen, C. K., N. Chandy, K. L. Kochuvarkey, P. K. Zacharia, P. J. Thomas, T. I. Ipe (1976) Unusual complication of snake bite: Hypopituitarism after viper bites. In Ohsaka A., K. Hayashi, Y. Sawai: Animal, plant and microbial toxins, Vol. 2. Plenum, New York: 467-73
• Matthai TP, Date A. Acute renal failure in children following snake bite. Ann Trop Paediatr. 1981 Jun;1(2):73-6. PMID: 6185055. https://doi.org/10.1080/02724936.1981.11748064
• Naik BN, Bhalla A, Sharma N, Mokta J, Singh S, Gupta P, Rai A, Subbiah S, Bhansali A, Dutta P. Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A prospective study. Neurol India. 2018 Sep-Oct;66(5):1351-1358. PMID: 30233002. https://doi.org/10.4103/0028-3886.241378
• Noutsos T, Currie BJ, Lek RA, Isbister GK. Snakebite associated thrombotic microangiopathy: a systematic review of clinical features, outcomes, and evidence for interventions including plasmapheresis. PLoS Negl Trop Dis. 2020 Dec 8;14(12):e0008936. PMID: 33290400; PMCID: PMC7748274. https://doi.org/10.1371/journal.pntd.0008936
• Noutsos T, Currie BJ, Wijewickrama ES, Isbister GK. Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice. Toxins (Basel). 2022 Jan 14;14(1):57. PMID: 35051033; PMCID: PMC8778654. https://doi.org/10.3390/toxins14010057
• Shivaprasad C, Aiswarya Y, Sridevi A, Anupam B, Amit G, Rakesh B, Annie PA, Anish K. Delayed hypopituitarism following Russell's viper envenomation: a case series and literature review. Pituitary. 2019 Feb;22(1):4-12. PMID: 30317419. https://doi.org/10.1007/s11102-018-0915-1
• Warrell DA. Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites. Trans R Soc Trop Med Hyg. 1989 Nov-Dec;83(6):732-40. PMID: 2533418. https://doi.org/10.1016/0035-9203(89)90311-8
• 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

Daboia siamensis (East of Bay of Bengal)

Described as: Daboia russelii formosensis

Taiwan

Case reports and case series .

• Kuo and Wu (1972)
  1 case; identification: morphological.
• Hung et al. (2002)
  18 cases; identification: the snake brought by the patient to the hospital or being witnessed by patients and the distinct clinical manifestation.
  Systemic envenoming 13/18 (72%)
• Hung et al (2006)
  13 cases; identification: ELISA.
• Mao et al. (2024)
  1 case and review.

Reviews

• Warrell (1989)
  Russell’s viper envenoming – geographical variation of clinical manifestations across SE Asia

Signs & symptoms
Autopharmacological effects
Increased capillary permeability 4/18 (22%) (Hung et al. 2002).
Local effects
Local pain or tenderness 17/18 (94%), swelling 17/18 (94%), limited to one joint 15/18 (83%), ecchymosis or bleeding at site of bite 17/18 (94%), necrosis 3/18 (17%) (Hung et al. 2002).
Haematological effect
Bleeding
Systemic bleeding 13/18 (72%), ecchymosis distant from bite site 11/18 (61%), bleeding from one/multiple organs 13/18 (72%) [GI tract 10/18 (56%) GU tract 11/18 (61&) Lung 5/18 (28%) CNS 1/18 (6%)]. Arterial thrombosis 2/18 (11%). Haemolysis 13/18 (72%) (Hung et al. 2002).
Muscular effects
Mostly mild rhabdomyolysis 9/18 (50%) (Hung et al. 2002).
Renal effects
Oliguria within 24 hours 18/18 (100%), acute renal failure 13/18 (72%) (Hung et al. 2002).
Multiple direct and indirect factors have been suggested to contribute to the development of acute renal failure: Direct venom toxicity, DIC leading to massive occlusion of the renal microvasculature with fibrin and ischemia, intravascular haemolysis. Only a few cases were noted to be hypotensive.
Renal function deteriorated despite antivenom treatment (Hung et al. 2002). 

Laboratory investigations 
Haemostasis
Coagulopathy 10/18 (56%) thrombocytopenia 13/18 (72%) (Hung et al. 2002)
Type of haemostatic defect
Venom-induced consumption coagulopathy (VICC)
Creatine kinase
Plasma CK level >10,000 m/l 2/18 (peak CK 10,890 and 27,821(Hung et al. 2002). 

References

• Hung DZ, Wu ML, Deng JF, Lin-Shiau SY. Russell's viper snakebite in Taiwan: differences from other Asian countries. Toxicon. 2002 Sep;40(9):1291-8. PMID: 12220714. https://doi.org/10.1016/s0041-0101(02)00137-x
• Hung DZ, Yu YJ, Hsu CL, Lin TJ. Antivenom treatment and renal dysfunction in Russell's viper snakebite in Taiwan: a case series. Trans R Soc Trop Med Hyg. 2006 May;100(5):489-94. PMID: 16325876. https://doi.org/10.101/j.trstmh.2005.07.020
• Kuo TP, Wu CS. Clinico-pathological studies on snakebites in Taiwan. Taiwan Yi Xue Hui Za Zhi. 1972 Jul 28;71(7):447-66. PMID: 4507795.
• Mao YC, Liu PY, Lai KL, Luo Y, Chen KT, Lai CS. Clinical Characteristics of Snakebite Envenomings in Taiwan. Toxins (Basel). 2024 Dec 30;17(1):14. PMID: 39852967; PMCID: PMC11769513. https://doi.org/10.3390/toxins17010014
• Warrell DA.Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites. Trans R Soc Trop Med Hyg. 1989 Nov-Dec;83(6):732-40. PMID: 2533418. https://doi.org/10.1016/0035-9203(89)90311-8

Described as: Daboia russelii siamensis 

Myanmar

Prospective study 

• Myint-Lwin et al (1985)
  123 Vipera russelli siamensis bites (= Daboia russelli siamensis). Identification: morphological 77/123 or immunological (Khin-Ohn-Lwin et al. 1984) 46/123.
• The data in the study of Myint-Lwin et al. 1985 refer either to the total number of verified bites (n = 123) or to the number of snakebite patients with systemic envenoming (n = 54).
• Than-Than et al (1989)
  3 patients who died from Vipera russelli siamensis bites (= Daboia russelli siamensis) (autopsy findings).
• Tun-Pe et al. (1987a)
  Part of the prospective studyMyint-Lwin et al (1985) above, investigating pituitary function.

See also cases and case series in “Laboratory and physical investigations” below.

Signs & symptoms
Autopharmacological effects
Vomiting 3/123, early occurrence of syncope as a consequence of arterial hypotension 2/123, within 90 min after the bite, spontaneous recovery within minutes. 12–24 h after the bite: conjunctival oedema 13/54, conjunctival haemorrhage 3/54, effusions (pleural, peritoneal) 1/54, pulmonary oedema (Myint-Lwin et al. 1985).
Hypovolaemia and shock due to extensive loss of fluid into the tissue (Than-Than et al. 1989).
The underlying pathophysiological mechanism is probably an autopharmacological release of endogenous mediators, histamine, 5-hydroxytryptamine, kinins and prostaglandins, or a direct effect of the venom on the vessel walls. These substances cause increased (generalised) capillary permeability. The altered capillary permeability might also cause brain oedema, which would explain the decreased consciousness, generalised cerebral seizures and focal neurological signs (Than-Than et al. 1989).
Local effects
Local pain 99/123, onset within minutes at the site of the bite.
Local swelling 84/123, maximum 1–4 days after the bite. Degree of swelling: grade 1: 49/123; grade 4 or 5: 9/123; grade 6: 1/123. Mean maximum increase in the circumference of the bitten extremity 4.0 cm ± 6.1%. Local swelling in patients with systemic envenoming more marked than in patients without systemic envenoming. However, 5/123 had systemic envenoming without local signs (Myint-Lwin et al. 1985).
Regional lymph nodes: pain 68/123, painful enlargement 66/123. Painful enlargement in patients with systemic envenoming 40/54 (Myint-Lwin et al. 1985).
Haematological effects
Bleeding
Persistent bleeding from bite marks 38/123, gingival bleeding 11/54, haematemesis 6/54, melaena 4/54, epistaxis 1/54, haematuria 39/54 (Myint-Lwin et al. 1985).
Haemoptysis (rare), menorrhagia and pre- and post-partum haemorrhaging (rare), intracerebral and subarachnoid haemorrhages (Warrell 1989).
Due to bleeding:
Clinical signs of hypopituitarism
Acute
Severe headache, shock, signs of hypoglycaemia and loss of consciousness, onset 21 h–9 days after the bite (Tun-Pe et al. 1987a). 
Chronic
Hoarse voice, low drive, reduced libido, oligo/amenorrhoea, impotence, absence of pubic hair, hyperpigmentation, signs of hypothyroidism, Addisonian crisis possible, diabetes insipidus (Tun-Pe et al. 1987a).
Pathophysiological cause most likely bleeding and deposition of fibrin microthrombi in the anterior hypophysis (Than-Than et al. 1989).
Renal effects 
Loin pain (signs of ischaemia) 9/54, renal bed sensitive to percussion (signs of ischaemia) 21/54, oliguria <400 ml/24 h 24/54; in 21/24 patients, the sensitivity of the renal bed preceded the oliguria and thus represents a valuable criterion for imminent renal failure (sensitivity 0.7, specificity 0.9) (Myint-Lwin et al. 1985).
49/119 (Tun-Pe et al. 1991) and 5/15 (Thein-Than et al. 1991) patients with systemic envenoming developed acute renal failure.
Kidney damage possible due to primary effects of the venom (Ratcliffe et al. 1989) or arterial hypotension (Myint-Lwin et al. 1985). However, the early acute renal failure seems to be primarily a consequence of ischaemia due to microthrombosis in the context of disseminated intravascular coagulation (Than-Than et al. 1989, Thein-Than et al. 1991).

Laboratory investigations
Haemostasis
Myanmar

Studies

• Than-Than et al. (1987)
  22 patients with Vipera russelli siamensis bites (= Daboia russelli siamensis) (identification: morphological) who showed no signs of systemic envenoming, such as systemic bleeding, local swelling or an abnormal clotting time, on admission to hospital 0.25–4 h after the bite. This patient population separated into 3 groups during the course of the observations.
  Group 1 (n = 5): no activation of the coagulation system that would have been detectable on the tests utilised.
  Group 2 (n = 6): sub-clinical activation of the coagulation system with minor abnormalities of some haemostatic parameters.
  Group 3 (n = 9): developed massive disseminated intravascular coagulation.
• Than-Than et al. (1988)
  42 patients with Vipera russelli siamensis bites (= Daboia russelli siamensis); identification: morphological or immunological (Khin-Ohn-Lwin et al. 1984): spontaneous systemic bleeding 23/42, hypotension 17/42, oliguria 15/42, of whom 5 died.

Type of haemostatic defect
Venom-induced consumption coagulopathy (VICC) 
Renal function
Studies

• Thein-Than et al. (1991)
  24 Vipera russelli siamensis bites (= Daboia russelli siamensis); identification morphological; prospective study.
  All patients had coagulable blood at the time of hospitalisation (0.5–6.5 h after the bite). 15/24 developed severe defibrin(ogen)ation within 3–5 days. 10 of these 15 had mild renal dysfunction; however, this returned to normal with antivenom treatment. The other 5, who were all already oliguric at the time of hospitalisation, developed acute renal failure despite administration of antivenom. Acute renal failure developed very rapidly after the bite. Albuminuria is already present in the first 24 h after the bite, sometimes even much earlier. In the 5 patients with acute renal failure, the albuminuria preceded the oliguria and is thus a suitable early indicator of acute renal failure.
• Tin-Nu-Swe et al. (1993)
  52 patients with V. r. siamensis bites who developed acute renal insufficiency (serum creatinine >1.3 mg/dl). Identification morphological and/or detection of specific venom antigen in the serum with ELISA; prospective study.
  Oliguria 32/52, urine output >400 ml/24 h 18/52. Oliguric patients more commonly had gastrointestinal bleeding, renal bed sensitive to percussion and conjunctival oedema, and the maximum serum creatinine values were significantly higher than in non-oliguric patients. The most likely cause of the renal dysfunction is proximal tubular necrosis.
• Alfred et al. (2019)
  686 patients. Identification: based on assumed snake identity.
  The publication shows the scale of the problem.

Acute and chronic hypopituitarism and diabetes insipidus
Acute
Hypoglycaemia, low levels of serum cortisol, plasma growth hormone and plasma prolactin (Tun-Pe et al. 1987a).
Chronic
Decreased levels of testosterone and thyroxine, diminished response of cortisol and growth hormone to hypoglycaemia (Tun-Pe et al. 1987a).
See also “Laboratory and physical investigations” below.
ELISA 
ELISA tests have been used in a number of studies in Myanmar for indirect identification of the cause of snakebite accidents (Khin-Ohn-Lwin et al. 1984, Myint-Lwin et al. 1985, Than-Than et al. 1988).
An improved ELISA test was used in a large study in Myanmar for indirect identification of the cause of snakebite accidents, in order to correlate the serum venom concentration with the severity of the envenoming and to investigate the dynamics of envenoming (Tun-Pe et al. 1991):
In 175 patients who did not bring the snake with them for identification, V. russelli was indirectly identified as the cause of the bite by an ELISA test in 101.
The serum venom antigen concentrations were higher in patients with systemic envenoming than in those with local symptoms of envenoming or an absence of symptoms. At the onset of the coagulation defect, they were higher the earlier after the bite the coagulation defect developed, and they increased as the coagulation defect developed. However, serum venom antigen concentrations cannot be directly correlated with the coagulability of the blood, as the assay does not only detect the fraction of the venom with a procoagulative action.
Furthermore, the measured serum venom antigen concentrations do not represent the actual amount of venom injected, as the venom undergoes tissue binding (Maung-Maung-Thwin et al. 1988). Venom is slowly released from a depot at the site of injection, so that the amount of venom measured in the serum also depends on the speed of absorption, which is influenced by various factors, including the muscular pump, which accelerates the transport of high-molecular weight venom components. The amount of venom measured is also dependent on the time period between the injection of venom and its measurement (Tun-Pe et al. 1991).

First aid
Tourniquets appear to be largely ineffective and even caused additional damage (Warrell 1989, Tun-Pe et al. 1987b).

Clinical Management
Arterial hypotension (systolic blood pressure <80 mmHg for >10 min)

• Myint-Lwin et al. (1985)
  Findings
  Patient characteristics: 19/123 became hypotensive within 4–38 h after the bite (on average 18.9 h). Mean lowest blood pressure after admission to hospital 60.2 mmHg (0–76 mmHg). 11 of the 19 hypotensive patients had clinical signs of bleeding: only gingival bleeding or bleeding from venipunctures or incisions (6/11), haematemesis (3/11), melaena (2/11). 10 of the 19 hypotensive patients developed oliguric renal failure (Myint-Lwin et al. 1985).
  Treatment
  Holding the head lower than the rest of the body and dextran 40 i.v., physiological salt solution and whole blood until the central venous pressure is 0 to +5 cmH₂O. Improvement of blood pressure through volume replacement therapy (11/19). If blood pressure did not improve with volume
  replacement therapy: dopamine 2–15 μg/kg body weight/min i.v. (infusion). Improvement of blood pressure with this treatment (6/7); in 1 of these patients, blood pressure was not measurable beforehand (Myint-Lwin et al. 1985).

Renal failure

• Myint-Lwin et al. (1985).
  Findings
  Patient characteristics: 24/123 developed oliguria. 21/123 patients who were hospitalised on average 5 h after the bite became oliguric on the 1st day in hospital, 3/123 on the 2nd and 3rd day
  Treatment
  Dialysis, if <400 ml urine/24 h despite rehydration, furosemide (up to 500 mg i.v.) and dopamine (2–5 μg/kg body weight/min) and if serum urea increasing. The prognosis for the recovery of renal function is good if the uraemic stage can be controlled with the help of dialysis (Myint-Lwin et al. 1985). In 10/28 oliguric patients treated with furosemide and dopamine, urine ouptut increased to >400 ml/24 h within 24–72 h. In 18/28 this treatment had no effect on urine output. The patients who did not respond to this treatment more frequently had spontaneous gingival bleeding and arterial hypotension (<80 mmHg) at the initial investigation and higher maximum blood urea levels and urine albumin concentrations. In none of the patients who responded to the furosemide/dopamine treatment was the renal bed sensitive to percussion or conjunctival oedema present. The time period between the bite and hospitalisation, as well as the initial venom antigen levels in the blood, were comparable between the two groups (Tin-Nu-Swe et al. 1993).

References

• Alfred S, Bates D, White J, Mahmood MA, Warrell DA, Thwin KT, Thein MM, Sint San SS, Myint YL, Swe HK, Kyaw KM, Zaw A, Peh CA. Acute Kidney Injury Following Eastern Russell's Viper (Daboia siamensis) Snakebite in Myanmar. Kidney Int Rep. 2019 May 29;4(9):1337-1341. PMID: 31517153; PMCID: PMC6732752. https://doi.org/10.1016/j.ekir.2019.05.017
• Antonypillai CN, Wass JA, Warrell DA, Rajaratnam HN. Hypopituitarism following envenoming by Russell's vipers (Daboia siamensis and D. russelii) resembling Sheehan's syndrome: first case report from Sri Lanka, a review of the literature and recommendations for endocrine management. QJM. 2011 Feb;104(2):97-108. PMID: 21115460. https://doi.org/10.1093/qjmed/hcq214
• Bhattacharya S, Krishnamurthy A, Gopalakrishnan M, Kalra S, Kantroo V, Aggarwal S, Surana V. Endocrine and Metabolic Manifestations of Snakebite Envenoming. Am J Trop Med Hyg. 2020 Oct;103(4):1388-1396. PMID: 32602439; PMCID: PMC7543852. https://doi.org/10.4269/ajtmh.20-0161
• Burke CW. The anterior pituitary, snakebite and Sheehan's syndrome. Q J Med. 1990 Apr;75(276):331-3. PMID: 2143590.
• Khin Ohn Lwin, Aye Aye Myint, Tun Pe, Theingie Nwe, Min Naing. Russell's viper venom levels in serum of snake bite victims in Burma. Trans R Soc Trop Med Hyg. 1984;78(2):165-8. PMID: 6464103. https://doi.org/10.1016/0035-9203(84)90267-0
• Myint-Lwin, Warrell DA, Phillips RE, Tin-Nu-Swe, Tun-Pe, Maung-Maung-Lay. Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment. Lancet. 1985 Dec 7;2(8467):1259-64. PMID: 2866333. https://doi.org/10.1093/qjmed/hcq214
• Noutsos T, Currie BJ, Lek RA, Isbister GK. Snakebite associated thrombotic microangiopathy: a systematic review of clinical features, outcomes, and evidence for interventions including plasmapheresis. PLoS Negl Trop Dis. 2020 Dec 8;14(12):e0008936. PMID: 33290400; PMCID: PMC7748274. https://doi.org/10.1371/journal.pntd.0008936
• Noutsos T, Currie BJ, Wijewickrama ES, Isbister GK. Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice. Toxins (Basel). 2022 Jan 14;14(1):57. PMID: 35051033; PMCID: PMC8778654. https://doi.org/10.3390/toxins14010057
• Pe T, Mya S, Myint AA, Aung NN, Kyu KA, Oo T. Field trial of efficacy of local compression immobilization first-aid technique in Russell's viper (Daboia russelii siamensis) bite patients. Southeast Asian J Trop Med Public Health. 2000 Jun;31(2):346-8. PMID: 11127337.
• Than Than, Khin Ei Han, Hutton RA, Myint Lwin, Tin Nu Swe, Phillips RE, Warrell DA. Evolution of coagulation abnormalities following Russell's viper bite in Burma. Br J Haematol. 1987 Feb;65(2):193-8. PMID: 3828227. https://doi.org/10.1111/j.1365-2141.1987.tb02264.x
• Than-Than, Hutton RA, Myint-Lwin, Khin-Ei-Han, Soe-Soe, Tin-Nu-Swe, Phillips RE, Warrell DA. Haemostatic disturbances in patients bitten by Russell's viper (Vipera russelli siamensis) in Burma. Br J Haematol. 1988 Aug;69(4):513-20. PMID: 3408687. https://doi.org/10.1111/j.1365-2141.1988.tb02408.x
• Than-Than, Francis N, Tin-Nu-Swe, Myint-Lwin, Tun-Pe, Soe-Soe, Maung-Maung-Oo, Phillips RE, Warrell DA. Contribution of focal haemorrhage and microvascular fibrin deposition to fatal envenoming by Russell's viper (Vipera russelli siamensis) in Burma. Acta Trop. 1989 Jan;46(1):23-38. PMID: 2566258. https://doi.org/10.1016/0001-706x(89)90013-2
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• Tin-Nu-Swe, Tin-Tun, Myint-Lwin, Thein-Than, Tun-Pe, Robertson JI, Leckie BJ, Phillips RE, Warrell DA. Renal ischaemia, transient glomerular leak and acute renal tubular damage in patients envenomed by Russell's vipers (Daboia russelii siamensis) in Myanmar. Trans R Soc Trop Med Hyg. 1993 Nov-Dec;87(6):678-81. PMID: 8296375. https://doi.org/10.1016/0035-9203(93)90290-7
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