Studies

Watt et al. 1988a: 39 Naja n. philippinensis bites; identification: specific antigen with ELISA 24/34 (34/39 were tested); exclusively morphological identification 4/39; by patients or relatives 4/39 and 7/39; with the exclusion criterion that there are no other medically significant neurotoxic snakes in the Philippines and the patients showed neurotoxic signs and symptoms.

Local envenoming:

• not present 14/39,
• minor (less than half of the bitten extremity affected) 21/39,
• extensive (more than half of the bitten extremity affected) 4/39.

Systemic envenoming:

• neurotoxic signs and symptoms 38/39.

Case reports

Watt et al. 1987a.

Signs & symptoms

Local effects

No local swelling 14/39; 6 patients displayed varying degrees of respiratory paralysis and 2 had to be intubated (Watt et al. 1988a). Also, bite marks may be undetectable (Watt et al. 1987a).

Minor local swelling 21/39; 1 patient developed superficial necrosis.

Extensive local swelling 4/39; 2 patients developed superficial necrosis (Watt et al. 1988a).

Neurological effects

Signs of paralysis 38/39; initial neurotoxic sign: ptosis 33/39, slurred speech 3/39, dysphagia 1/39, respiratory dysfunction 1/39. Varying degrees of respiratory paralysis, which was always associated with ptosis and glossopharyngeal paralysis 18/39 (Watt et al. 1988a).

Over a third of patients with neurotoxic signs and symptoms had no local swelling; this was the case even though sometimes drastic first aid measures had been used and a tourniquet was normally applied (Watt et al. 1988a). The time interval between the bite and the first neurotoxic sign or symptom was 1 h (0.05–24 h), ptosis 1 h (0.05–24 h), glossopharyngeal paralysis 1.8 h (0.08-30 h) and respiratory paralysis 1.3 h (0.17–2 h) (Watt et al. 1988a).

Cardiac effects

Arrhythmias and arterial hypotension in several patients with respiratory paralysis: secondary causes (hypoxia) likely (Watt et al. 1988a) (see also Laboratory and physical investigations below, 2. ECG).

Other signs & symptoms

Vomiting 12/39 (Watt et al. 1988a).

Drowsiness 4/39. Can be difficult to distinguish from ptosis and requires careful questioning of the patient; possibly a reason for the low incidence of this symptom compared to other Asian cobra bites (Watt et al. 1988a).

Case fatality rate

53.8/100,000 inhabitants/year; average age 17 years; 98% men (usually rice farmers). Only 8% of bite victims reach a hospital (Watt et al. 1987b).

2/39; 1 patient died 2 h after the bite, and the other 4 h afterwards (Watt et al. 1988a).

3 patients died within 30 min after the bite due to respiratory failure (Watt, unpublished observations, cited in: Watt et al. 1989).

Morbidity

3/39 patients developed local, superficial necrosis; in 1 patient a finger was amputated (Watt et al. 1988a). However, overall only minor local morbidity after Philippine cobra bites, e.g. compared to those of Malaysian cobras.

Laboratory and physical investigations

1. Leucocytes
Leucocytosis, on average 11,062/mm³ (2,600–18,700/mm³) (Watt 1988a).

2. ECG
Performed in 13/39 patients and was conspicuous in only 3 patients. 2 had ST segment elevations, 1 had sinus bradycardia. In all 3 patients the ECG changes persisted during observation in hospital and on follow-up examinations (no convincing indications of primary cardiac effects of the venom) (Watt et al. 1988a).

3. ELISA
N. n. philippinensis venom antigen detectable 24/34 (Watt et al. 1988a).

First aid

Study
Watt et al. 1988b: prospective study with 36 patients who had been bitten by Naja n. philippinensis, had had a 'tourniquet' applied and who developed neurotoxic signs and symptoms. Identification: specific antigen with ELISA 24/36 (additional morphological identification in 2 of these patients); with the aid of photos and the snake's behaviour (spread hood) 4/36; only morphological 2/36; with the exclusionary diagnosis that there are no other medically important neurotoxic snakes in the Philippines 6/36. Definition of a 'tourniquet': any type of wide band or ligature located proximal to the site of the bite.

Finding: 'Tourniquets' delay the systemic uptake of cobra neurotoxins. This effect is maintained for a long period (in one case the neurological signs worsened after the tourniquet was removed after 30 h) (Watt et al. 1988b).

When the tourniquet was removed abruptly, 11/34 noticed a sudden intensification of their neurological symptoms within 10 min; 4/34 developed symptoms for the first time. Respiratory arrest occurred in 4/34 patients within 10 min; 1 of these patients had been asymptomatic until then (Watt et al. 1988b).

Treatment (symptomatic)

1. Endotracheal intubation and artificial respiration are the most important measures in the case of respiratory insufficiency. The paralytic effect of cobra venom is reversible with time (Watt et al. 1989).
2. Edrophonium (Tensilon®) and long-acting anticholinesterase inhibitors (e.g. neostigmine methylsulphate).

Studies

Watt et al. 1986: placebo-controlled study (10 mg edrophonium after prior administration of 0.6 mg atropine sulphate vs. placebo) with 20 patients who had been bitten by Naja n. philippinensis and showed clear neurotoxic signs of envenoming. Identification: specific antigen with ELISA 9/10, in 1 case the snake was also available for identification; with the aid of photos and the behaviour of the snake (spread hood) 1/10.

Watt et al. 1989: study design see below.

Efficacy

By means of the Tensilon® test, the efficacy of neostigmine can be reliably predicted (Watt et al. 1986). Administration of edrophonium (Tensilon®) 2 h after the patient received antivenom was significantly more effective than antivenom and either completely reversed signs of paralysis or at least caused a significant improvement (Watt et al. 1989). Neurological signs and symptoms could be controlled with a dose of neostigmine adjusted for the individual patient. There was improvement of expiratory and inspiratory pressure, forced vital capacity and the ability to cough, speak and swallow, as well as improvement of ptosis and upward gaze. Before administration of treatment and under placebo treatment, EMG findings corresponded to those for myasthenia gravis and normalised with edrophonium. No serious side effects of edrophonium or neostigmine were observed in any patient. Abdominal pain was recorded most frequently, but this was manageable with atropine (Watt et al. 1986).

Treatment (specific)

Antivenom

"Cobra" (Serum and Vaccine Laboratories, Rizal).

Studies
Watt et al. 1989: double-blind study with 8 patients who had been bitten by Naja n. philippinensis and displayed clear neurotoxic signs of envenoming. Identification: specific antigen with ELISA 5/8; with the aid of photos and the behaviour of the snake (spread hood) 2/8; with the exclusionary diagnosis that there are no other medically important neurotoxic snakes in the Philippines 1/8.

Dose
20, 50 or 100 ml of antivenom were administered i.v. over 30 min. 2 h later 10 mg of edrophonium was administered after the patients received 0.6 mg of atropine sulphate (see above, Symptomatic treatment 2.)

Efficacy

1. None of the administered antivenom doses caused a clinically relevant improvement in the neurological signs and symptoms within 2 h, in contrast to edrophonium (Tensilon®) (see above), despite a high anti-neurotoxin antibody titre and good neutralising capacity in a mouse bioassay; it may be that higher doses of antivenom are necessary, in order to achieve accelerated dissociation of neurotoxin-acetylcholine receptor complexes via neurotoxin-specific antibodies (Boulain and Menez 1982). Another explanation may be that a low-molecular-weight fraction of the venom, which is, for example, almost exclusively responsible for the lethal effect of the venom of Naja n. sputatrix in Malaysia (Nget-Hong 1983), is not present in sufficient concentrations in the antivenom, which is produced by injecting horses with raw venom.
   The results of the few studies on the efficacy of antivenom in neutralising the neurotoxic effects of cobra bites in Southeast Asia are contradictory. In two of these studies the effect is also not impressive (Reid 1964, Viravan et al. 1986, Watt et al. 1989).
2. The efficacy of antivenom on the formation of local necroses is questioned (Reid 1964, Homma and Tu 1970). However, there are no prospective studies to this purpose. With Naja n. philippinensis bites, in contrast to bites of other Asian cobras, the problem of necrosis formation is anyhow generally insignificant (Watt et al. 1988a, 1989).

Adverse reactions

Immediate hypersensitivity (0/8) (Watt et al. 1989).
Delayed serum sickness (1/8) (Watt et al. 1989).

Indications for antivenom
With the tested doses (up to 100 ml), the effect of the antivenom on clinical improvement of neurological symptoms is so minor that the indication for administration of antivenom as opposed to treatment with anticholinesterase inhibitors and artificial respiration is highly questionable (Watt et al. 1989).