Studies

Northwest Malaysia
Reid 1964: 47 N. naja ssp. bites; identification: morphological by Reid: N. n. leucodira (= N. kaouthia) 45/47, N. n. kaouthia 2/47 (Viravan et al. 1986: "Reid's 47 patients were bitten by cobras morphologically similar to N. n. kaouthia, but mistakenly described as N. n. leucodira").

• no envenoming 21/47,
• negligible envenoming: local swelling, but no necrosis 4/47,
• necrosis: local necrosis, but no systemic effects 16/47,
• systemic envenoming (neurotoxic) 4/47; these patients also developed necroses; 2/47 died.

Method for measuring difference in circumference: measurement of the circumference of the bitten extremity and the healthy extremity in centimetres (rounded up or down to the nearest 0.5 cm) at the same level on the hands or feet, or the wrists or ankles (narrowest part), and the upper arms or thighs (middle). The 4 respective measurements are added together and the difference is calculated.

Thailand
Viravan et al. 1986: Naja n. kaouthia bites (N. kaouthia or N. siamensis); identification: ELISA detection of N. n. kaouthia venom antigen in serum 22/24; positive ELISA detection and morphological identification of the dead snake 11/22, only positive ELISA identification 11/22; only morphological identification of the dead snake 2/24.

No envenoming 2/24.

Only local swelling 8/24; local necrosis 7/24.

Systemic envenoming (ptosis and other neurotoxic signs of envenoming) 14/24; all 7 patients who developed local necroses also had neurotoxic signs of envenoming.

Compared to Reid (1964), this study had a significantly lower percentage of patients without signs of envenoming, which is due to methodological factors, among others. As detection of venom antigen in serum requires a minimum amount of injected venom, the severe cases of envenoming are over-represented (Viravan et al. 1986) (see also below: Regional differences in symptoms of envenoming).

Case reports

Sawai 1987

Regional differences in symptoms of envenoming

On the basis of observations made to date, it would seem that N. kaouthia causes more necrotic and fewer neurotoxic effects in northwest Malaysia compared to Thailand (Viravan et al. 1986).

Signs & symptoms

Autopharmacological effects

Urticaria of the face and extremities with fever in the first 2 days after the bite (1/47). This patient received neither medication nor antivenom (Reid 1964).

Local effects

Pain: in most patients, pain commences immediately after the bite. The duration of the pain, which is felt as severe, correlates with the extent of necrosis (necrosis <100 cm²: on average 3 days; ≥100–600 cm²: on average 10 days) (Reid 1964).

Swelling: commences 2–3 h after the bite, at the latest 24–48 h after the bite (Reid 1964). The speed at which the swelling spreads and its extent are generally less than with Calloselasma rhodostoma bites.

If there is no local swelling within >1 h after the bite, it is almost certain that envenoming has not occurred (Reid 1964). All patients with systemic envenoming had local swelling at the site of the bite (Viravan et al. 1986).

Initially, the local swelling is a dirty colour around the area of the bite marks, which spreads from day to day. On the 3rd–4th day this grey-black area is surrounded by a red edge which sometimes has small blisters in it, while blood-filled blisters often form in the centre. After 4–5 days the swelling fluctuates, and after incision, the necrotic area becomes visible and reveals necrosis of a greater extent than is indicated by the superficial changes. The necrosis extends into the subcutaneous tissue. In light of this, there is a danger that a local envenoming is initially regarded as harmless. Experience has shown, however, that necrosis occurs in almost all cases (Reid 1964). It is thus necessary to make sure the patient is observed for a sufficient length of time.

Frequency of swelling and necrosis as local signs of envenoming in the populations studied (see above: studies of Reid 1964, Viravan et al. 1968).

10 of 12 patients who died due to respiratory failure after N. n. kaouthia bites had local swelling with or without the formation of blisters (Looareesuwan et al. 1988).

Neurological effects

Ptosis, dysarthria, dysphagia, ophthalmoplegia, which commenced 3–4 h after drowsiness began (see below), i.e. 4–9 h after the bite, occurred in all patients with systemic envenoming (by definition). Generalised weakness as a sign of paralysis of the skeletal musculature was last to occur (Reid 1964). Paralysis of the respiratory musculature with respiratory failure (Viravan et al. 1986, Sawai 1987).

All patients with systemic envenoming displayed ptosis ((Viravan et al. 1986).

Frequency of neurotoxic signs of envenoming in the populations studied (see above: studies of Reid 1964, Viravan et al. 1968).

In one study of fatal snakebites in rural areas of Thailand, 12 of 46 fatalities were due to N. n. kaouthia bites. Respiratory failure was the cause of death in all cases; 10 of 12 had local swelling (Looareesuwan et al. 1988).

Cardiac effects

Arterial hypotension 1/4 (concurrent ECG changes: see Laboratory and physical investigations below) (Reid 1964) (primary/secondary cardiotoxic effect?).

Other signs & symptoms

Vomiting 5/20, abdominal pain 3/20. There was no difference in the incidence of these two symptoms between patients with only local envenoming and those with systemic envenoming (Reid 1964).

Drowsiness occurred in all patients with systemic envenoming, beginning 1–5 h after the bite, and was the earliest sign of systemic envenoming (6/6) (Reid 1964). Difficult to differentiate between this and ptosis. Careful questioning of the patient is thus necessary (Watt et al. 1988).

Case fatality rate

2/47 (Reid 1964).

In 14 lethal bites in Malaysia (1955–1961), the average time between the bite and death was 12.6 h. If one discounts 3 cases with an unusually long time between the bite and death, the average time was 4.6 h (1¼–8½ h) (Reid 1964).

4/58 patients with a suspected cobra bite (N. n. kaouthia was confirmed to be the cause of the bite in 24 of these 58 cases). Amongst the fatalities, an N. n. kaouthia bite was confirmed by the ELISA method in 3/4 (surprisingly, in 1 case  B. fasciatus venom antigen was found in the serum). Death occurred 2–3 h after the bite and was attributed to respiratory failure (Viravan et al. 1986).

According to a study of fatal snakebites in rural areas of Thailand, 12/46 died from N. n. kaouthia bites. Respiratory failure was the cause of death in all cases (Looareesuwan et al. 1988). Of 4,850 snakebites recorded over a period of 5 years in Thailand, 25% were caused by N. n. kaouthia, 6.5% were fatal (Trishnananda 1979).

Morbidity

Nearly all patients who are injected with a significant amount of venom develop necroses, even if local symptoms initially look only mild (see above). Split-thickness skin grafting is necessary in all cases where there is extensive skin loss (Reid 1964, Sawai 1987).

The time it took for necrosis to heal completely differed according to the extent of the necrosis, and was on average 6 weeks (<10 cm²), 12 weeks (>10 cm², <100 cm²) or 15 weeks (≥100 cm²). The administration of antivenom had no effect on the course of the necroses (Reid 1964).

Laboratory and physical investigations

1. Haemostatic parameters
Clotting time, clot quality test, prothrombin time, platelet count unaffected (Reid 1964).

2. Haemoglobin
Decrease in haemoglobin of 2–3 g/100 ml, which was preceded by an increase in serum bilirubin of 2–3 mg/100 ml and urobilinogen in the urine in the first few days after the bite.

Increase in reticulocytes in 3/6 patients with systemic envenoming (Reid 1964).

3. Leucocytes
Leucocytosis in the first few days in patients with severe systemic envenoming (Reid 1964).

4. Proteinuria
In 6/6 patients with systemic envenoming for 2–4 days. No evidence of haemoglobin or myoglobin in the urine. Serum urea normal, except for 1 patient with a slight increase on the 5th day and normalisation on the 9th day. Urinary output unaffected in all patients (Reid 1964).

5. ECG
ECG performed in 13/13 patients with only local envenoming (necroses), normal in all cases. Pathological changes in 1 patient with systemic envenoming: ST segment elevation in the right precordial leads, followed later by T wave inversions. Concurrent arterial hypotension was present. 7 days after the bite the ECG was normal again  (Reid 1964) (primary/secondary cardiotoxic effect?).

6. ELISA
22/58 suspected cobra bites were confirmed with the ELISA method. Specific venom antigen was detected in 14/20 (70%) of the patients with systemic envenoming and in 8/33 (24%) of the patients with only local envenoming  (Viravan et al. 1986). As detection of venom antigen in the serum requires a minimum quantity of venom to have been injected, mild cases of envenoming cannot be reliably verified. However, even in the sera of 6/20 patients with systemic (neurotoxic) signs of envenoming, no N. n. kaouthia venom antigen was found, nor B. candidus venom antigen, but in 1 of these 6 patients a high concentration of B. fasciatus venom antigen was detected. This patient had received monovalent cobra antivenom and died. This underlines the importance of the ELISA method for differentiating neurotoxic symptoms. This is especially important in countries (such as Thailand) where only monovalent antivenoms are available (Viravan et al. 1986). At the same time it is necessary to be cautious with the use of this method for the exclusion of a particular cause of envenoming, due to problems with the sensitivity of the method, as no antigen was detected in 5/20 patients with systemic signs of envenoming.

7. Bacteriology
In 4/47 patients, culture of blister contents and excised material from necrotic areas was performed. Staphylococcus aureus was isolated in 1 patient, and Proteus (among others) in the other 3 patients (Reid 1964).

Treatment (symptomatic)

Endotracheal intubation and artificial respiration: successful (Sawai 1987).

Treatment (specific)

Antivenom

Cobra antivenom (QSMI, Bangkok).

Efficacy 

1. Local envenoming
   Cobra antivenom (QSMI, Bangkok) (4 patients), polyvalent antisnake venom serum (Haffkine, Mumbai) (6 patients). Dose: 50 ml (20–150 ml) in most cases: local necroses were neither prevented nor improved.
2. Systemic envenoming
   Cobra antivenom (QSMI, Bangkok) (4 patients), polyvalent antisnake venom serum (Haffkine, Mumbai) (6 patients): condition improved in patients with systemic envenoming, but not dramatically, possibly due to insufficient doses of antivenom (Reid 1964).
   Cobra antivenom (QSMI, Bangkok): 19 patients with systemic (neurotoxic) envenoming. Administered dose on average 240 ml (40–470 ml), from which it can be concluded that this antivenom does not show any convincing efficacy in neutralising neurotoxic effects. However, the data are inconsistent, and a well-planned clinical study is urgently required in order to clarify the efficacy of antivenom for the treatment of N. n. kaouthia bites (Viravan et al. 1986). 

Adverse reactions

Cobra antivenom (QSMI, Bangkok): 3/4 patients who received this antivenom developed immediate hypersensitivity, severe in 1/3, moderately severe in 2/3; delayed serum sickness in 4/4 (Reid 1964).

Polyvalent antisnake venom serum (Haffkine, Mumbai): 1/6 patients who received this antivenom developed moderately severe immediate hypersensitivity and 0/6 patients suffered delayed serum sickness (Reid 1964).

Recommendations
Indications for antivenom
Clinical signs of systemic envenoming:
1. paresis,
2. drowsiness with or without arterial hypotension (Reid 1964).

Dose
Minimum 100 ml i.v. (Reid 1964).