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.

Arterial hypotension due to the release of histamine and bradykinin has been described with some Bothrops species (Kaiser and Michl 1971).

Tourniquets can cause local swelling and mimic local venom effects.

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

Swelling that involves large areas of an extremity or the entire extremity and that extends to the trunk carries the risk of development of hypovolaemic shock due to sequestration of large volumes of fluid.

The efficacy of antivenom with regard to local effects, in particular swelling and necrosis, is also a matter of controversy in South America and has even been called into question entirely. The neutralising capacity of the available antivenoms with regard to those venom components that possess haemorrhagic and myonecrotic activity is most probably small, as these effects occur rapidly after the injection of venom (Gutierrez 1990).

Bothrops sp.: if no swelling develops, it is most unlikely that clinically relevant envenoming has occurred. In a series of B. moojeni bites, 32/34 patients developed local swelling within 30 min after the bite, and all patients within 2 h (Kouyoumdjian and Polizelli 1988, Gutierrez 1990).

The local effects caused by Bothrops sp. venoms are myonecrosis, bleeding and oedema. Damaged musculature regenerates to some extent. However, in many cases regeneration is deficient due to changes in the microcirculation (Gutierrez 1990, Gutierrez and Lomonte 1989).

Lachesis sp: marked local effects with extensive swelling.

Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites in the northeastern Amazon region of Brazil with 74 patients included 45 confirmed Bothrops atrox bites and 1 confirmed Lachesis muta bite. Pain and swelling at the site of the bite were present in 74/74 patients on admission (Pereira de Oliveira Pardal et al. 2004).

Bites from C. durissus ssp. in the southern regions of the distribution area of this species represent an important exception to the rule that clinically relevant envenoming can be excluded following bites by Viperidae (viperids and crotalids) if local swelling is absent (see also the Biomedical database entry for Crotalus durissus ssp., Clinic section: "Regional differences in symptoms of envenoming due to C. durissus ssp.").

Micrurus sp.: local swelling either does not develop at all or is insignificant.

Even extensive swelling of the extremities is not necessarily an indication of compartment syndrome. There are no reports of patients with objectively identified compartment syndrome (measurement of compartment pressure). The decision to perform a fasciotomy must have a rational basis (evidence of increased intra-compartmental pressure; reduced or absent arterial blood flow).

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 is ineffective, one of the possible reasons may be misidentification of the snake that caused the bite, in particular if a monovalent antivenom was used.

The procoagulative components of the venoms of Bothrops sp. cause more marked haemostatic defects than those of Crotalus durissus and Lachesis sp. Bothrops sp. venoms activate factor X and prothrombin and have direct fibrinogen-coagulating activity, while Crotalus durissus ssp. and Lachesis sp. venoms, in contrast, only have a direct effect on fibrinogen. Furthermore thrombopaenia is not uncommonly observed in cases of Bothrops sp. envenoming (Kamiguti and Cardoso 1989, Sano-Martins 1990). Haemorrhagic activity has been described in particular for the venom of Bothrops sp., but also for Lachesis muta ssp. venoms (Mandelbaum 1990).

This means that clinically significant haemorrhages are theoretically more likely to occur following Bothrops sp. and Lachesis sp. bites than with Crotalus durissus ssp. bites. Documented cases with haemorrhagic complications appear to confirm this (see the Biomedical database entries for B. jararaca and B. moojeni).

There are no controlled clinical studies from South America on the efficacy of antivenom for the treatment of neurological effects of the venom. The effect of the currently available and clinically proven antivenoms on neurotoxic signs of envenoming is not very convincing and, if present at all, is slow to occur (Watt 1992). Already established neurological effects of envenoming cannot be reversed with antivenom and only improve very slowly (Rosenberg 1971).

If neurological symptoms persist for longer than 30 min after the initial dose of antivenom, the dose is repeated (Warrell 1990b).

At the same time, the possibility of misidentification of the snake that caused the bite must always be kept in mind (see below), in particular if a monovalent antivenom was 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. Artificial respiration, 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). In some cases this may avoid the need for artificial respiration (see the Biomedical database entry for Micrurus sp.).

Envenoming caused by Crotalus durissus terrificus (and possibly C.durissus collilineatus and other subspecies) causes paralyses.

The venoms of various Micrurus species appear to impair neuromuscular transmission in different ways, and thus it can be expected that cholinesterase inhibitors will have varying degrees of efficacy (Brazil 1990).

There are no systematic investigations of the efficacy of acetylcholinesterase inhibitors. Their use is recommended (Bucaretchi 1990).

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

Up to 1985 Crotalus durissus ssp. venom was considered to have a haemolytic effect because myoglobinuria was incorrectly identified as haemoglobinuria on the basis of urine investigations. Now it is clear that only rhabdomyolysis is involved.

The observed enzyme pattern (CK/MB, LDH1) is not due to myocardial damage (see the Biomedical database entry for C. durissus ssp.).

Following a B. moojeni bite, raised CK levels (max. 1,269 IU/l) were observed in one patient who had neither applied a tourniquet nor received an i.m. injection (Nishioka and Silveira 1993). However, these findings are not necessarily an indication of rhabdomyolysis, as they could also be explained by local myotoxic effects (see the Biomedical database entry for B. moojeni).

There are no reports of envenoming from South America that indicate a primary cardiac effect of the venoms of South American elapids and crotalids. Secondary cardiac involvement is to be expected in patients with rhabdomyolysis and renal failure (hyperkalaemia).

Enzyme patterns that mimic a myocardial infarction can occur following C. durissus terrificus bites (pseudo-infarction enzyme patterns) (see above).

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

Following C. durissus terrificus bites, rhabdomyolysis is a factor that favours the development of acute renal failure (Ward 1988). Acute renal failure is also a commonly observed complication following Bothrops sp. bites.

In most cases acute renal failure occurs as a consequence of acute tubular necrosis. The prognosis is good, as long as there is adequate medical care (dialysis, fluid and electrolyte balance). In the case of renal cortical necrosis, which has also been observed, the prognosis depends on the availability of long-term dialysis treatment and the possibility of a renal transplant. 

Two external characteristics of the crotalids and elapids are so obvious that identification of these snakes can be made relatively reliably, and they also make it possible to distinguish between the two genera:

• the rattle on the end of the tail: Crotalus sp. (see Find terrestrial snake by morphology (regional)),
• the markings and colouring: Micrurus sp. (see Fig. 4.56).

In addition, differentiation according to symptom complexes can aid regional identification (see Clinical flowchart: South America and the West Indies):

• Local swelling, incoagulable blood, systemic bleeding:
  
  • crotalids: Bothrops sp., Lachesis sp.,
  • colubrids.
• Muscle pain, signs of paralysis of the cranial nerves, the extremities and the respiratory musculature, incoagulable blood (systemic bleeding), renal failure:
  
  • crotalids: C. durissus terrificus and possibly C. durissus collilineatus.
    
• Signs of paralysis of the cranial nerves, the extremities and the respiratory musculature:
  
  • elapids: Micrurus sp.

Controlled clinical studies from South America on the efficacy of antivenom are scarce.

A randomised study comparing 3 anti-crotalid antivenoms was performed in Brazil (Cardoso et al. 1993). There are also empirical data for antivenom treatment of B. moojeni (Kouyoumdjian and Polizelli 1988) and Crotalus durissus terrificus bites (Silveira and Nishioka 1992, Cupo et al. 1988, 1990).

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.

See Antivenom treatment.