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.

The venoms of Protobothrops flavoviridis and Daboia russelli in particular can cause hypotensive shock within minutes after the bite and hypovolaemic shock within hours (note that such reports are primarily from Myanmar). The most common cause of death from Protobothrops flavoviridis bites is shock (Sawai 1989).

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

For some species of snakes local signs of envenoming, in particular swelling, are a reliable parameter for possible systemic envenoming, 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 also controversial in the Far East.

Necrosis develops after Cobra bites: N. atra, but also Ophiophagus hannah; and after crotalid bites: Gloydius sp., Deinagkistrodon acutus, Trimeresurus sp. (in the old taxonomic sense). Especially marked necrosis with large tissue defects and permanent severe functional impairment has been described in Japan (Amami Islands) following Protobothrops flavoviridis bites and in Taiwan following Deinagkistrodon acutus bites.

There are no reports from the Far East of compartment syndrome.

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.
    

The haemostatic defects caused by crotalids in the Far East are primarily due to direct activation of fibrinogen ("thrombin-like" activity), while those caused by D. russelli are due to procoagulative venom components (DIC).

Even coagulation disorders that are severe according to laboratory tests may only be clinically apparent to a slight degree, or not at all. 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 misidentification of the snake that caused the bite, especially if monospecific antivenoms were used.

The efficacy of the currently available and clinically tested antivenoms with regard to neurological effects 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, a further dose should be given (Warrell 1990b).

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:

• 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.
• 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) (Watt 1992).

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

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

• Antivenom,
• symptomatic treatment:
  
  • treatment of the acute renal failure.

Acute renal failure is the most common cause of death from Gloydius blomhoffii bites (Sawai 1989).

With Daboia russelli and Rhabdophis sp. bites, acute renal failure is most probably primarily associated with renal ischaemia resulting from DIC. Periods of arterial hypotension also play a role.

However, a direct nephrotoxic effect of Daboia russelli venom has also been discussed (Ratcliffe et al. 1989).

Difficulties arise if only monospecific antivenoms are available and the snake that caused the bite needs to be identified at the species level in order to be able to choose the appropriate antivenom.

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: The Far East):

Signs of paralysis of the cranial nerves, extremities and respiratory musculature with no or minimal local effects:

• Elapids: Bungarus sp.

Signs of paralysis of the cranial nerves, extremities and respiratory musculature, sometimes with marked local effects:

• Elapids:
  • Naja atra,
  • Ophiophagus hannah,
  • Naja kaouthia ?
    
• Crotalids: G. blomhoffii (+ possible bleeding, acute renal failure).

Haemostatic defects (abnormal clotting time) with spontaneous bleeding and local effects:

• Viperids: Daboia russelli.

• Crotalids: several Trimeresurus sp. (in the old taxonomic sense), Deinagkistrodon acutus.

• Colubrids: Rhabdophis sp.

Local effects, hypotensive shock in the early phase (bleeding?) (clotting time normal):

• Crotalids:
  • G. blomhoffii (+ signs of paralysis and acute renal failure),
  • Protobothrops flavoviridis.

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 up to several days after initial treatment, and blood coagulability should continue to be monitored twice daily.

The same considerations apply to patients suffering from elapid bites.

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

• Physiotherapy,
• surgical correction.

Local treatment.

See Antivenom treatment.