Is it an Emergency?

Inquire

• time of the bite,
• local pain,
• nausea, vomiting, abdominal pain.

Assess

• state of consciousness.

Measure

• blood pressure/pulse,
• respiratory rate,
• oxygen saturation (pulse oximeter),
• 20WBCT (bedside test).

Observe/investigate

• bite marks,
• extent and intensity of local swelling,
• eyes: conjunctivitis, corneal lesions, uveitis (spitting cobras!),
• enlargement and painfulness of regional lymph nodes,
• swelling in the facial region, including the larynx/pharynx (angio-oedema),
• conjunctival oedema,
• clinical signs of a pleural effusion, pulmonary oedema,
• clinical signs of shock,
• bleeding in the region of the swelling,
• bleeding from bite marks and other injuries,
• gingival bleeding,
• blood-stained sputum, vomit ("coffee ground vomitus"), stools (melaena) or urine,
• acute abdomen (intra-abdominal bleeding!),
• focal neurological deficits, meningismus (intracranial bleeding!),
• cranial nerve deficits, such as ptosis, ophthalmoplegia, dysphagia, dysarthria,
• paralysis of the skeletal musculature including the respiratory musculature (→ respiratory insufficiency/respiratory failure),
• myalgia with active and passive movement and upon pressure,
• dark-brown/red urine (differential diagnosis haemoglobinuria)(rhabdomyolysis!),
• flank pain and renal bed sensitive to percussion,
• severe headache, shock (refractory arterial hypotension), signs of hypoglycaemia and loss of consciousness (acute pituitary/adrenal insufficiency).

Varibility of symptoms and degree of envenoming

The symptoms and degree of envenoming depend not only on the amount of venom injected and numerous other variables, but also on the time that has elapsed since the bite. This variable factor must be taken into account when making the following decisions:

• exclusion of envenoming 
• the time interval between clinical examinations
• emergency care (see below)

Bite marks and dry bites

The fact that a patient has been bitten by a known venomous snake and the presence of bite marks do not automatically allow the conclusion that a clinically relevant injection of venom has taken place. A substantial proportion (up to 50 % are reported) of confirmed bites, including cobra bites, proceed with no detectable symptoms or at the most negligible local signs of envenoming.

Autopharmacological signs & symptoms

“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) 

CLS is unique for Russell's viper envenoming and includes chemosis, periorbital, and facial oedema, bilateral parotid swelling, 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 (Warrell and Williams 2023).

Local signs & symptoms

Daboia sp.: on the whole, local signs of envenoming caused by D. russelii bites are quite mild compared to those of other viperids and in relation to the severity of the systemic envenoming. D. russelii is an important exception to the rule that a viperid bite can be excluded if local swelling is absent (Warrell 1989).

Echis sp.: local swelling may be mild. 

Calloselasma rhodostoma: absence of swelling or only mild local swelling virtually excludes systemic injection of venom (Reid et al. 1963a).

Ophiophagus sp. and Naja sp. (with the exception of Naja philippinensis): if local swelling does not occur within hours of a N. kaouthia bite, envenoming can effectively be ruled out (Reid 1964). All patients with systemic envenoming had swelling as a local sign (Viravan et al. 1986). In contrast, over a third of patients with N. philippinensis bites and a neurotoxic course of envenoming had no local swelling (Watt et al. 1988a).

Bungarus sp.: as a rule there are no local signs of envenoming. On average, the extent of swelling and the speed with which it spreads following Cobra bites that cause local effects are lower than with Calloselasma rhodostoma bites in particular (Reid 1964).

Compartment syndrome

Even massive swelling, such as occurs in particular following Calloselasma rhodostoma bites, only rarely causes compartment syndrome. The decision to perform a fasciotomy must have a rational basis see (Compartment syndrome). 

Necrosis

Necrosis is often a consequence of cobra bites that cause local effects in particular, likewise Calloselasma rhodostoma bites.

Local effects (eyes)

Venom ophthalmia from Asian species are considered less severe than that from African species. 
Intense local pain; Blepharospasm; Palpebral oedema; Leucorrhoea; photophobia, clouding of vision, temporary blindness
(Chu et al. 2010, Warrell 2023, WHO 2016).

Abdominal pain

Krait bites in particular may be completely unnoticed and unrecognised initially, as these snakes often bite people at night while they are asleep. A krait bite is thus an important differential diagnosis of signs of paralysis (of the cranial nerves, extremities, respiratory musculature).
Abdominal pain is recognized as a characteristic symptom of kraits.

Non-clottable blood and bleeding

Clinically evident signs of a haemostatic defect may be absent. Nonetheless defibrin(ogen)ation may be present to such a degree that the blood is completely incoagulable. For this reason the simple clotting time test should always be performed if a viperid or crotalid bite is suspected.

Even coagulation disorders that are severe according to laboratory tests may only be clinically apparent to a slight degree, or not at all (in particular following Echis sp., Calloselasma rhodostoma and Trimeresurus sp. bites). There is a threat of spontaneous haemorrhage with extensive loss of blood or focal bleeding (e.g. intracranial) as long as the haemostatic defect exists (untreated, i.e. without antivenom treatment, days to weeks). 

Acute, delayed and chronic pituitary or adrenal insufficiency and diabetes insipidus

To date, acute pituitary/adrenal insufficiency has been reported in Myanmar, southern India and Sri Lanka. 

Hypopituitarism following Daboia siamensis and Daboia russelii envenoming (Antonypillai et al 2011, Warrell and Williams 2023).

Acute signs

Acute pituitary-adrenal insufficiency is suspected in patients with bleeding, neurological features of hypoglycaemia, or refractory shock (Warrell and Williams 2023). Onset 21 h–9 days after the bite (Anatonypillai et al. 2011).

Delayed hypopituitarism (Shivaprasad et al 2019). 

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).

Pituitary dysfunction in survivors (Naik et al 2018).

Thrombotic microangiopathy (TMA)

TMA is regularly observed in Daboia bites and includes disseminated intravascular coagulation, microangiopathic haemolytic anaemia. TMA with acute kidney injury is recognised in patients envenomed by Daboia sp. and other species.

Descending paralysis / Respiratory failure

Patients remain conscious even when completely paralysed. Communication may still be possible by moving fingers on commands.
Bungarus sp. and Naja sp.: Life-threatening respiratory failure. 
Daboia russelii (Sri Lanka, South India): Mostly mild neuromuscular dysfunction with no long-term effects.

Acute kidney injury (AKI) and chronic kidney injury

Daboia sp.: “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).

Monitoring for signs and symptoms that would indicate systemic envenoming for at least 24 h.

At least hourly

• state of consciousness,
• ptosis,
• heart rate and rhythm,
• blood pressure,
• respiratory rate,
• bleeding,
• local swelling,
• other newly appearing signs and symptoms.

6-hourly (or more frequently if there is cause for suspicion)

• 20WBCT (bedside test),
• labortaory-based clotting tests (see above),
• CK, GOT (AST),
• urine output.

The absence of signs of envenoming in the first hours after the bite does not exclude the possibility that a relevant injection of venom has taken place. There may be a long delay before systemic signs of envenoming develop. Moreover, the continued absorption of venom from the region around the site of the bite can lead to renewed symptoms of systemic envenoming even after successful administration of antivenom (e.g correction of the haemostatic defect).