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Diagnosis & Treatment — Hospital

 

Autopharmacological effects

S  Signs & Symptoms
  • Abdominal colic, vomiting, diarrhoea,
  • angio-oedema,
  • dyspnoea, bronchospasm,
  • arterial hypotension and shock.
D  Diagnostics

Clinical.

T  Treatment
  • Treatment of the anaphylactic/anaphylactoid shock,
  • possibly antivenom.
S  Signs & Symptoms

Generalised tissue oedema (increased capillary permeability!).

D  Diagnostics

Clinical.

T  Treatment
  • Antivenom,
  • treatment of the hypovolaemia/hypovolaemic shock.
S  Signs & Symptoms
  • Non-cardiogenic pulmonary oedema,
  • cerebral seizures (cerebral oedema),
  • (increased capillary permeability!).
D  Diagnostics
  • Clinical,
  • physical investigations:
    • chest X-ray,
    • CCT.
T  Treatment
  • Antivenom,
  • treatment of the non-cardiogenic pulmonary oedema/cerebral oedema.
C  Comments

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.

Species of snakes in North Africa and the Near and Middle East that cause autopharmacological effects

C  Comments

The venom of vipers in particular can cause clinical symptoms of anaphylaxis in patients within minutes after the bite.

Autopharmacological effects of venom such as arterial hypotension and hypovolaemic shock as a consequence of sequestration of large amounts of fluid in the extravascular space occur with Bitis arietans, Vipera palaestinae and Macrovipera sp.? in particular (Efrati 1979, Leviton et al. 1992, Warrell et al. 1975).

Local effects

S  Signs & Symptoms
  • Local swelling that can extend to the trunk,
  • local signs of haemorrhage (ecchymosis),
  • long-term sequelae: necrosis that can involve the subcutaneous tissue and musculature,
  • external eye: conjunctivitis, corneal lesions, uveitis.
D  Diagnostics
  • Clinical:
    • extent and intensity of the swelling,
    • inspection of the eyes (spitting cobras!).
  • Split lamp, fluorescein stain (spitting cobras!).
T  Treatment
  • Antivenom:
    • as long as there are concurrent signs of systemic envenoming,
    • if extensive or rapidly progressive swelling is present, especially with snakebites from those species known to cause necrosis (Warrell et al. 1975, 1976b, Tilbury 1982).
  • Symptomatic treatment:
    • fluid replacement if there is extensive or rapidly progressive swelling.
C  Comments

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.

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, such as swelling and necrosis, has not been proven. The small amount of data that is available is not sufficient to assess this (Warrell et al. 1975, 1976b, 1977, Tilbury 1982).

Species of snakes in North Africa and the Near and Middle East that cause local effects

In the eyes:

C  Comments

Atractaspis sp.: as a rule there is generally at least mild local swelling following injection of venom (Warrell et al. 1976c).

Bitis arietans: marked local swelling that often extends to the trunk and causes necrosis (Warrell et al. 1975, Marsh and Whaler 1984).

Causus sp.: local swelling generally appears to occur following injection of venom, but is only marked in a small proportion of cases (Warrell et al. 1976c).

Echis sp.: local swelling always occurs if venom has been injected, but may be only mild (Porath et al. 1992, Warrell et al. 1977).

Daboia palaestinae and Macrovipera lebetina: extensive swelling that may extend to the trunk, necrosis possible but rarely severe as long as the bite is not on the fingers or toes (Efrati 1979, Leviton et al. 1992).

Naja nigricollis and N. pallida: local swelling may be very extensive, possibly involving the trunk, necrosis (Warrell et al. 1976b).
Naja haje: local signs of envenoming usually absent or insignificant (Warrell et al. 1976b, Blaylock et al. 1985, Visser and Chapman 1978).

Walterinnesia aegyptia: local swelling (Yayon et al. 1988).
Eyes:
Naja nigricollis, N. pallida, N. katiensis and N. nubiae can cause lesions in the eye (Warrell and Ormerod 1976).

Compartment syndrome

D  Diagnostics
T  Treatment

Treatment of the compartment syndrome (see surgical literature).

C  Comments

Even extensive swelling, such as occurs following Bitis arietans, V. palaestinae and Macrovipera lebetina bites, is not usually a manifestation 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).

Haemostatic effects

S  Signs & Symptoms
  • Bleeding from injuries (apart from bite wounds),
  • bleeding into the skin (ecchymosis, petechiae),
  • gingival bleeding, epistaxis,
  • haematemesis, haemoptysis, bleeding per rectum, including melaena, haematuria (macro/micro),
  • clinical signs of shock (haemorrhagic shock!),
  • acute abdomen (intra-abdominal bleeding!),
  • flank pain/renal bed sensitive to percussion (ischaemia, renal haemorrhage!),
  • focal neurological signs, meningismus (intracranial bleeding!),
  • pale sclerae (anaemia due to bleeding and (haemolytic anaemia)).
D  Diagnostics
  • Clinical,
  • laboratory parameters:
    • Hb, Hct,
    • clotting time,
    • PT/aPTT,
    • TT,
    • fibrinogen,
    • FSP,
    • D-dimers,
    • platelets,
    • blood group/blood sample for cross-matching.
T  Treatment
  • 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.
C  Comments

Even coagulation disorders that are severe according to laboratory tests may only be clinically apparent to a slight degree, or not at all (e.g. Echis 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). 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 and venom-induced coagulation disorders are present, spontaneous systemic bleeding should cease within 1530 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 always necessary to consider the possibility of treatment failure or misidentification of the snake that caused the bite.

Haematuria (especially microhaematuria) is not a reliable sign of a venom-induced haemorrhage in those regions where urinary schistosomiasis (Schistosoma haematobium) is prevalent.

Species of snakes in North Africa and the Near and Middle East that cause haemostatic / haemolytic defects

Neurological effects

S  Signs & Symptoms
  • Cranial nerve paralysis, such as ptosis, opthalmoplegia, dysphagia, dysarthria.
  • Paralysis of the skeletal musculature, including the respiratory musculature, with respiratory insufficiency/respiratory failure.
D  Diagnostics
  • Clinical,
  • physical investigations:
    • blood gas analysis,
    • forced expiration test (peak expiratory flow).
T  Treatment
C  Comments

There are no controlled clinical studies of the efficacy of antivenoms for snakebites in this region that cause neurological effects. In Southeast Asia the efficacy of antivenom with regard to neurological effects (Cobras, Kraits) has been more thoroughly investigated. The effect is not convincing and, if present at all, is slow to occur (Warrell 1990b).

Apart from the problem of antivenom efficacy, the possibility of misidentification of the snake that caused the bite must always be considered if the expected treatment effect does not occur.

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).

Species of snakes in North Africa and the Near and Middle East that cause neurological effects

C  Comments

In 4 definite cases of Walterinnesia aegyptia bites no signs of paralysis were observed (Yayon et al. 1988). Corkill (1931–33) reported neurotoxic symptoms following bites by Walterinnesia morgani; however, the snakes that caused the bites were not identified with certainty.

Muscular effects

There are no known species of snakes in North Africa and the Near and Middle East whose venom causes rhabdomyolysis.

Cardiac effects

S  Signs & Symptoms
  • Cardiac dysrhythmias,
  • cardiac insufficiency/failure.
D  Diagnostics
  • Clinical,
  • blood pressure, pulse,
  • ECG.
T  Treatment
  • Antivenom,
  • symptomatic treatment.
C  Comments

ECG changes have been observed following Echis coloratus bites (Fainaru et al. 1974).

Cardiac dysrhythmias and cardiac insufficiency and failure are probably usually secondary effects (hyperkalaemia, in the context of shock).

 

Species of snakes in North Africa and the Near and Middle East that cause cardiac effects

Renal effects

S  Signs & Symptoms
  • Flank pain, renal bed sensitive to percussion,
  • eyelid oedema,
  • oliguria/anuria, polyuria.
D  Diagnostics
  • Clinical,
  • urine output (balance, hourly),
  • laboratory parameters:
    • serum creatinine,
    • serum potassium,
    • serum bicarbonate.
T  Treatment
  • Antivenom,
  • symptomatic treatment:
    • treatment of the acute renal failure.

Species of snakes in North Africa and the Near and Middle East that cause renal effects

C  Comments

According to the available data, acute renal failure following a snakebite in North Africa and the Near and Middle East generally appears to be a secondary effect (arterial hypotension, shock, DIC).

For Bitis arietans and Cerastes cerastes venom a primary nephrogenic effect is discussed (Warrell et al. 1975, Schneemann et al. 2004).

How is the appropriate antivenom chosen?

D  Diagnostics
C  Comments

In many regions of North Africa and the Near and Middle East, polyspecific antivenoms are available that cover the medically relevant snake species; however, sometimes monospecific antivenoms need to be utilised as well.

If the snake that caused the bite needs to be identified at the species level in order to choose the appropriate antivenom, indirect criteria must often be used, as 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: North Africa, Near and Middle East):

  • Signs of paralysis of the cranial nerves, extremities and respiratory musculature:
    Elapids: Naja haje, N. arabica?, N. melanoleuca?, N. senegalensis?, N. oxiana?, Walterinnesia aegyptia?
  • Incoagulable blood (clotting time test), spontaneous bleeding, local swelling:
    Viperids: Echis sp., Cerastes cerastes
  • Marked local swelling that may involve the trunk, necrosis, hypovolaemic shock, spontaneous bleeding (clotting time normal):
    Viperids: Bitis arietans, (Cerastes cerastes)
  • Marked local swelling that may involve the trunk, hypovolaemic shock, (spontaneous bleeding), (necrosis):
    Viperids: Vipera palaestinae, Macrovipera lebetina
  • Marked local swelling that may affect the entire extremity and the trunk, (necrosis):
    Elapids: Naja nigricollis, N. pallida, N. katiensis?, N. nubiae?
  • Mild swelling (→ necrosis):
    Viperids: Causus sp. (no antivenom available!); Atractaspis sp. (no antivenom available!).
  • Local signs of envenoming in the eye:
    Spitting cobras: N. nigricollis,  N. pallida, N. katiensis, N. nubiae.

 

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.

Controlled clinical studies of antivenom efficacy only exist for a small number of antivenoms (see Biomedical database).

How are antivenoms administered and complications caused by antivenoms treated?

T  Treatment

Monitoring of the patient

1. After administration of antivenom (assessment of success of antivenom or indication for continued antivenom treatment)

D  Diagnostics

Specific examinations are based on the signs and symptoms as well as laboratory parameters that were used to determine the indications for antivenom administration.

Viperids:

  • Echis sp., Cerastes cerastes: systemic bleeding, clotting time test, more complex haemostatic tests.
  • Bitis arietans, (Cerastes cerastes): systemic bleeding, hypovolaemic/shock parameters, platelets.
  • Vipera palaestinae, Macrovipera lebetina: hypovolaemic/shock parameters.

Elapids:

  • N. haje, other elapids?:
    • spontaneous breathing,
    • signs of respiratory insufficiency,
    • fist grasp,
    • upward gaze,
    • forced expiration test.

 

C  Comments

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.

2. If there is no indication for antivenom treatment following the initial investigation

D  Diagnostics

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):

Follow-up
1. Wounds, in particular necrosis

D  Diagnostics
  • Inspection,
  • bacterial smears.
T  Treatment
  • Excision of necrotic material,
  • surgical debridement under general or regional anaesthesia, 
  • skin grafting (split-thickness).

2. Contractures and other forms of impairment or loss of function of the extremities

D  Diagnostics

Clinical.

T  Treatment
  • Physiotherapy,
  • surgical correction.

3. Eyes (corneal lesions)

D  Diagnostics
  • Split lamp,
  • fluorescein stain.
T  Treatment

4. If antivenom was administered: serum sickness

D  Diagnostics
T  Treatment
C  Comments

In particular with Cobra bites that cause local effects (N. nigricollis, N. pallida, N. katiensis, N. nubiae), the true extent of the necrosis is often only discernible after some time, and thus it is essential that the patient is observed for a sufficiently long period in order to ensure the necessary treatment.

Corneal lesions and lesions of the anterior chambers of the eye need to be either definitively excluded or treated systematically in order to avoid damage due to secondary infections.