In most cases the cause of autopharmacological reactions is the direct toxin-induced release of biogenic amines. Immediate hypersensitivity reactions (type I) appear to be rare.

An effective antivenom will improve the cardiovascular symptoms of envenoming, which are largely of autopharmacological origin, within 10–20 min (Warrell 1990b).

Hypovolaemic shock as a consequence of generalised fluid sequestration in the extravascular space due to increased capillary permeability occurs in particular with D. russelli siamensis bites in Myanmar.

Tourniquets can cause local swelling and thus mimic local venom effects.

For some species of snakes local signs of envenoming are a reliable parameter for injection of venom, while for other species they provide no indication at all.

The efficacy of antivenom with regard to local effects, such as swelling and necrosis, is controversial.

Daboia russelii ssp.: 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. Around one fifth of patients with systemic envenoming had only local oedema (Bhat 1974).

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

Ophiophagus hannah 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 C. rhodostoma bites in particular (Reid 1964).

Necrosis: necrosis is often a consequence of Cobra bites that cause local effects in particular, likewise C. rhodostoma bites.

Even massive swelling, such as occurs in particular following C. rhodostoma bites, only causes compartment syndrome in a very few cases. The decision to perform a fasciotomy must have a rational basis (evidence of increased intra-compartmental pressure; reduced or absent arterial blood flow).

• Antivenom.
• Symptomatic treatment:
  
  • Whole blood.
  • Replacement of clotting factors and platelets following antivenom administration to bridge the gap until the antivenom starts being effective, insofar as evident bleeding or the imminent threat of critical bleeding makes this necessary. Also in cases where antivenom is not available or is ineffective and bleeding or the risk of bleeding makes intervention necessary (Warrell 1990b). However, it is important to note that replacement of clotting factors and platelets is only effective in the short-term while circulating haemostatically active venom components are still present. 
  • Treatment of the haemorrhagic shock.
    

A lack of treatment success may be due to misidentification of the snake that caused the bite. This is a danger in particular in those cases in which monovalent antivenoms are used. There are reports from Thailand of cases where large amounts of monospecific Daboia russelli antivenom were administered under the assumption that the bite was caused by D. russelli, and after revision of the species identification (C. rhodostoma) and administration of the appropriate monovalent antivenom, there was immediate treatment success (Brown and Brown 1988).

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, Calloselasma and Trimeresurus 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). The risk is even greater if a patient does not receive appropriate treatment at a hospital and is then exposed to trauma, even very minor trauma, for example while working.

Loss of large volumes of blood can occur due to blood oozing from the bite wound or from injuries or due to medical or paramedical intervention.
If antivenom is effective, spontaneous systemic bleeding should cease within 15–30 min, and blood coagulability should be restored within 1–6 h. The clotting time test is a simple means to regulate the antivenom dose. The initial dose should be repeated if the blood is still not coagulable 6 h after the first dose (Warrell 1990b).

If antivenom treatment is not successful, it is necessary to consider the possibility of insufficient efficacy of the antivenom if the snake that caused the bite was identified correctly.

Blood transfusions.

The efficacy of the currently available antivenoms with regard to neurotoxic signs of envenoming is not very convincing and, if present at all, is slow to occur (Watt 1992). If the neurological symptoms persist for longer than 30 min after the initial dose, this is repeated (Warrell 1990b). See also the relevant Biomedical database entries: Bungarus sp., Naja naja, N. kaouthia, N. phillipinensis, Doboia russelii pulchella.

At the same time, it is always necessary to consider the possibility of misidentification of the snake that caused the bite (see below), especially if monovalent antivenoms were used.

Due to the highly questionable efficacy of antivenom against neurotoxic symptoms of envenoming, the other two available treatment approaches need to be used concurrently and in a timely manner:

• The edrophonium (Tensilon®) test should be performed immediately in every patient with signs of paralysis, in order, if the result is positive, to make the most of the improvement in neuromuscular transmission that can be achieved through use of a longer-acting acetylcholinesterase inhibitor (neostigmine). In some cases this may avoid the need for artificial respiration (Watt 1992).
• Endotracheal intubation and artificial respiration: endotracheal intubation is certain to prevent any form of aspiration. Manual or mechanical ventilation, even though it may have to be employed over a long period of time, can ensure survival of a patient with neurotoxin-induced respiratory failure.

There is no antivenom for Bungarus candidus. Moreover, there is no paraspecific efficacy of other monovalent Bungarus antivenoms. Haffkine polyspecific antivenom is of questionable value (see the Biomedical database entry).

Misidentification of B. candidus as B. fasciatus (although they have easily distinguishable characteristics) has led to patients being given large amounts of "ineffective" monovalent B. fasciatus antivenom following B. candidus bites, and the patients dying before the snakes were correctly identified (Looareesuwan et al. 1988).

Haffkine antivenom shows no convincing effects on the neurotoxic aspects of Daboia russelli pulchella envenoming.

• Antivenom,
• symptomatic treatment:
  • prevention of myoglobinuric nephropathy,
  • immobilisation (regeneration of the damaged musculature).

The efficacy of Haffkine antivenom has not been demonstrated.

Cardiac dysrhythmias and cardiac insufficiency or failure are usually secondary effects (hyperkalaemia from various causes; in the context of shock).

• Naja philippinensis: no conclusive indication of primary cardiotoxicity (Watt 1988a).
• Naja kaouthia: a possible cardiotoxic effect in isolated patients (Reid 1964).
• Echis carinatus: ECG: T wave inversion (Bhat 1974) (see the Biomdedical database entry for E. carinatus sochureki).

Acute renal failure is primarily associated with renal ischaemia resulting from DIC. Periods of arterial hypotension also play a role. For Daboia russelli ssp. venom, however, a direct nephrotoxic effect has also been discussed (Ratcliffe et al. 1989).

In the distribution area of Daboia russelli ssp. acute renal failure has been observed primarily in Myanmar, southern India and Sri Lanka and occasionally in northern India and Thailand.

In Rangoon Daboia russelli ssp. bites are the most common cause of acute renal failure (Warrell 1990b).

In many regions of Southeast Asia the snake that caused the bite needs to be identified at the species level in order to be able to use the appropriate antivenom (monospecific antivenoms!).

This is made difficult by the fact that in the majority of cases the snake is not available for identification or the patient's description of the snake is not conclusive.

Differentiation according to symptom complexes can aid regional identification (see Clinical flowchart: Indian Subcontinent and Southeast Asia:

Cranial nerve deficits and paralysis of the skeletal musculature including the respiratory musculature:

• Elapids (Kraits, Cobras): in this region these snakes may cause local effects in addition, or exclusively local manifestations, including extensive necrosis. This does not apply to Naja philippinensis (Philippines).
• Viperids (Daboia russelli pulchella): haemostatic effects occur in addition, and local swelling may also be present.

Incoagulable blood (clotting time test), spontaneous bleeding, local swelling:

• Vipers:
  
  • Daboia russelli ssp.: N.B.: local swelling may be absent, e.g. with Daboia russelli ssp. bites in Sri Lanka and Myanmar;  D. russelli pulchella causes paralysis in addition.
  • Echis sp.
• Crotalids:
  
  • Calloselasma rhodostoma,
  • Trimeresurus sp. (according to the old classification)
    
• (Colubrids). 

Eye injuries:

• Spitting cobras.

If the selected antivenom is not effective, 3 possible causes need to be considered:

1. correct identification of the cause, but insufficient dose administered;
2. correct identification of the cause, but inadequate efficacy of the antivenom;
3. incorrect identification of the cause → revision of identification.

Even if the desired effect of antivenom administration, namely normalisation of the parameters relevant to envenoming (findings on physical examinations, physical and laboratory investigations), is achieved quickly, this does not mean that the symptoms of envenoming may not re-occur due to continued absorption of venom from a depot in the region of the bite.

Patients bitten by species of snakes whose venom causes haemostatic defects should be kept in hospital for several days after initial treatment, and blood coagulability should continue to be monitored twice daily. A further hospital stay of at least 5 days was suggested for patients given antivenom treatment for defibrin(ogen)ation syndrome caused by Calloselasma rhodostoma (Warrell et al. 1986).

• Excision of necrotic material,
• surgical debridement under general or regional anaesthesia, 
• skin grafting (split-thickness).

• Surgical correction,
• physiotherapy.

Local treatment.

With Cobra bites in particular, a patient may be discharged from hospital before necrosis becomes evident (see the Biomedical database entry for Naja kaouthia).

Corneal lesions need to be either definitively excluded or treated systematically in order to avoid permanent damage due to secondary infections.