Studies

Nigeria
Warrell et al. 1976b: 14 N. nigricollis bites; identification: morphological (7/14) or immunological with ELISA (Greenwood et al. 1974) (7/14).

Local envenoming:

1. Extent of the swelling (grade 1–6; scale of Warrell et al. 1974):

Grade 1  3/14
Grade 2  1/14
Grade 3  1/14
Grade 4  1/14
Grade 5  4/14
Grade 6  4/14

2. Intensity of the swelling (measurement method of Reid et al. 1963c): maximum difference in circumference between the bitten extremity and the healthy extremity on average 12.6 cm (4.7–18.4 cm) or 14.9% (3.8–27%).

Warrell and Ormerod 1976: 9 N. nigricollis bites; identification: patient history ("spitting" cobra was seen) and ophthalmological findings.

Case reports

Côte d'Ivoire: Chippaux et al. 1978.

Signs & symptoms

Local effects

Local swelling 14/14; swelling reached a maximum within 36 h after the bite (see above for degree and extent). On average it took 11 days (1–18 days) for the swelling to disappear completely (Warrell et al. 1976b). Enlarged, painful lymph nodes (10/14). Painfulness of the lymph nodes was an early sign that appeared as early as 30 min after the bite (Warrell et al. 1976b).

Blistering 8/14, beginning 4 h to 5 days after the bite. Blistering was always followed by necrosis (Warrell et al. 1976b).

Local necroses 10/14, usually appearing around the 5th day after the bite (36 h to 10 days). Necroses at times so extensive that they led to loss of the entire soft tissue covering of the affected extremity (Warrell et al. 1976b).

Accidents in which venom entered the eye: conjunctivitis 5/9, corneal ulceration 4/9, anterior uveitis, i.e. absorption of venom into the anterior chamber of the eye 1/9, permanent blindness (failure to treat symptoms, e.g. corneal ulceration) 2/9 (Warrell and Ormerod 1976).

Haemostatic effects

Spontaneous haemorrhage 3/14,  subarachnoid haemorrhage 1/3 (observed 36 h after the bite), gingival bleeding 1/3 (observed 16 h after the bite), epistaxis 1/3 (observed 72 h after the bite); microhaematuria in the absence of urogenital schistosomiasis 1/14 (Warrell et al. 1976b).

Other signs & symptoms

Diminished consciousness 3/14; one of these patients had pulmonary oedema and died, another had a subarachnoid haemorrhage and also died, and the third regained full consciousness after several hours (Warrell et al. 1976b).

Case fatality rate

2/14; cause: subarachnoid haemorrhage 1/2, uncertain cause 1/2 (Warrell et al. 1976b).

Morbidity

Local necroses 10/14, at times so extensive that they led to loss of the entire soft tissue covering of the affected extremity. Untreated wounds are prone to secondary infection. If treatment is not timely or adequate (debridement, split-thickness skin grafting, antibiotic treatment), amputation of the whole limb is often unavoidable. A further problem are chronic recurrent ulcers that carry a risk of becoming malignant (Warrell et al. 1976b).

Accidents in which venom entered the eye: conjunctivitis, corneal ulceration, anterior uveitis, permanent blindness (failure to treat symptoms, e.g. corneal ulceration) 2/9 (Warrell and Ormerod 1976).

Laboratory and physical investigations

1. Haemostasis

Type of haemostatic defect
Platelet dysfunction (in vitro: MacKay et al. 1969, cited in Warrell et al. 1976b); no proven effect of venom components on blood clotting in humans.
Possible activation of blood clotting and vascular impairment through activation of complement (Warrell et al. 1976b).

2. Leucocytes
Neutrophil leucocytosis, on average 16,000/mm³  (Warrell et al. 1976b).

3. Complement
C3 ↑, GBG ↑ (possible activation of blood clotting and vascular impairment through activation of complement) (Warrell et al. 1976b).

4. ELISA (Greenwood et al. 1974)
Crucial contribution to identifying the snake that caused the bite if the snake is not available for morphological identification. In particular, ELISA allows differentiation from Bitis arietans, which has probably been incorrectly blamed for a considerable number of envenoming cases caused by N. nigricollis (Warrell et al. 1976b).

Treatment (symptomatic)

1. Pain: codeine phosphate (Warrell et al. 1976b).
2. Necroses: debridement 7/14 and split-thickness skin grafting 4/14 (Warrell et al. 1976b).
3. Patients with necroses and wound incisions before hospitalisation: procaine-penicillin, anti-tetanus serum (1,500 units) (Warrell et al. 1976b).
4. Accidents in which venom enters the eye: rinse the eye immediately with water, prevention of secondary infections (local antibiotic treatment, atropine). Thorough examination of the eye (fluorescein test, split lamp: corneal ulceration, changes in the anterior chamber of the eye) in order to identify patients at risk, who must be looked after diligently until the lesions have healed (Warrell and Ormerod 1976).

Treatment (specific)

Studies
No controlled clinical studies available. Data regarding the efficacy of antivenom in the report of Warrell et al. 1976b.

Antivenoms

Utilised by Warrell et al. 1976b:
Behringwerke North and West Africa, polyvalent (Bitis, Echis, Naja)
FitzSimons', polyvalent (Bitis, Hemachatus, Naja)
South African Institute for Medical Research (SAIMR), polyvalent (Bitis, Dendroaspis, Hemachatus)

Indications for administration of antivenom
Systemic signs of envenoming 11/14 (Warrell et al. 1976b).

Dose

Doses of 20–80 ml administered in the study of Warrell et al. (1976b).

Efficacy

1. With regard to local effects: increase in swelling despite administration of antivenom up to a total dose of 80 ml (5/11) (Warrell et al. 1976b).
2. With regard to the development of necroses: development of necroses despite administration of antivenom up to a total dose of 80 ml (8/11) (Warrell et al. 1976b).
3. With regard to the haemostatic effect (haemostatic defect found in laboratory investigations): impaired clot retraction and elevated FSP despite administration of antivenom.
4. With regard to eye injuries in accidents in which venom enters the eye: systemic administration of antivenom is not indicated, no proven value of local application of antivenom (Warrell et al. 1976b).

Adverse Reactions

Immediate-type allergic reaction 4/11, pyrogenic reaction 2/11 (Warrell et al. 1976b).

Evaluation and recommendations
The antivenom doses administered in this study had no demonstrable effect on the N. nigricollis venom. The available study is not able to answer these two crucial questions: 1. What represents a sufficient dose of antivenom? 2. Which effects are neutralised by the available antivenoms?

Until these questions are answered, it is recommended that a minimum dose of 80 ml of antivenom that includes Naja sp. in its specific spectrum of activity be administered following a N. nigricollis bite, provided that swelling is present that extends over more than half of the affected extremity, regardless of whether or not there are systemic signs of envenoming (Warrell et al. 1976b).