Studies

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)

Malaysia (Penang)

Reid 1975b

Patients were included in the clinical part of this study if they had systemic symptoms of envenoming after E. schistosa (16 patients), Hydrophis cyanocinctus (3 patients) and Hydrophis spiralis (3 patients) bites.

The great majority of bites were caused by E. schistosa. In the years 1957–1964, 101 patients who had suffered bites conclusively determined as being caused by a sea snake were cared for under the direction of A. Reid, most in Penang General Hospital. In only 10 cases was the snake available for identification: E. schistosa 7, H. cyanocinctus 1, H. spiralis 1, K. jerdoni 1. 71 patients identified the snake that had bitten them by choosing from amongst live sea snakes that were shown to them. This gave the following results: E. schistosa 55/101, H. cyanocinctus 14/101, H. spiralis 9/101, K. jerdoni 1/101, L. hardwickii 2/101, not identified 20/101.

Proportion of the individual genera of 4,735 sea snakes that were caught over a distance of up to 10 miles from the coast of Penang Island between 1960 and 1963: E. schistosa 2,403, H. cyanocinctus 1,074, H. spiralis 349, K. jerdoni 188, L. hardwickii 115.

Circumstances of the bite: only 12/101 patients were not fishermen. Of these 12, 10 were bitten while swimming, although all 10 were not actually swimming but rather wading at the time they were bitten.

Classification: for the definition of no/mild/severe/fatal envenoming, see below "Signs and symptoms".

Enhydrina schistosa
No envenoming: 39/55,
Mild envenoming: 4/55,
Severe envenoming: 5/55,
Fatal envenoming: 7/55.

For comparison, cases of envenoming caused by the other genera:

Hydrophis cyanocinctus
No envenoming: 11/14,
Mild envenoming: 2/14,
Severe envenoming: 1/14.

Hydrophis spiralis
No envenoming: 6/9,
Mild envenoming: 3/9.

Kerilia jerdoni
No envenoming: 1/1.

Lapemis hardwickii
No envenoming: 2/2.

Not identified
No envenoming: 9/20,
Mild envenoming: 2/20,
Severe envenoming: 8/20
Fatal envenoming: 1/20.

Time interval between the bite and admission to hospital:
≤0.5 h: 5/101; 1 of whom died,
0.5–1 h: 8/101; 1 of whom died,
1–2 h: 15/101; no deaths,
2–4 h: 27/101; no deaths,
4–6 h: 27/101; no deaths,
6–10 h: 11/101; 3 of whom died,
>10 h: 8/101; 3 of whom died.

No antivenom treatment
58/101 (from 1957–1961 antivenom was not available): fatal envenoming: 6/58; severe envenoming: 5/58; mild envenoming: 6/58; no signs of envenoming: 41/58.

Antivenom treatment
43/101 (from 1962–1964 antivenom was available): fatal envenoming: 2/43; severe envenoming: 9/43; mild envenoming: 5/43; no signs of envenoming: 27/43.

Case reports

Malaysia (Penang)
Enhydrina schistosa
Reid 1957: identification: morphological; Reid himself was bitten.
Reid 1962: identification: morphological.

Japan

Hydrophis cyanocinctus
Higa et al. 1990: identification: morphological.

Signs & symptoms

Local effects

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)

Apart from an initial stabbing pain, no local signs or symptoms! (Reid 1975b, 1979).

Neurological effects

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
E. schistosa: the venom contains only short-chain neurotoxins that require tryptophan at position 187 of the acetycholine receptor in order to be effective. This is not present in humans. This makes it clear that the venom of E. schistosa cannot cause primary neurotoxic effects in humans, in contrast to many animals (Harris 1989, Minton 1990). However, in human envenoming a myotoxic phospholipase A is active, which causes the clinical signs and symptoms in the skeletal musculature described below under "Muscular effects" (Fohlman and Eaker 1977).

Muscular effects

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Mild envenoming: in most cases no clinical signs or symptoms apart from elevated serum AST (see below "Laboratory and physical investigations").

In some cases onset of myalgia within 0.5–3.5 h after the bite. Myalgia never very marked and remains localised in around half the cases, in the other half it becomes generalised within 0.5 h. 1–4 h after the bite moderate pain may be caused by passive movement of the skeletal musculature. Symptoms disappear completely within 1–3 days.

Severe envenoming: in these cases the latency period before the onset of symptoms of envenoming is always <2 h (if no efficient tourniquet was applied after the bite). The symptoms correspond to those of mild envenoming with the difference that they start earlier and are more severe. Symptoms become generalised after 0.5 h. Dysphagia and dysphonia very marked.

At the physical investigation 1–2 h after the bite the patient lies in bed with arms bent and legs outstretched. Passive movements are very painful. Neurological investigations (grip and pinch strength, deep tendon reflexes) are normal in most cases.

Dark, red, brown or black urine first becomes evident after 3–8 h.

After several more hours actual (flaccid) paralysis (of the peripheral type) may occur: ptosis, ophthalmoplegia, inability to stick out the tongue or swallow and to keep the head upright. Posture can no longer be controlled. Deep tendon reflexes can no longer be elicited. Respiratory distress may occur due to the impairment of the respiratory musculature. However, patients are generally fully conscious.

Course (if no antivenom administered): the myalgia and myoglobinuria reach a maximum 1 week after the bite. Paralyses continue to deteriorate during this period. Grip and pinch strength returns in the 3rd week, and deep tendon reflexes in the 3rd or 4th week (for the further course, see below "Morbidity").

Fatal envenoming: aspiration may occur due to glossopharyngeal paralysis. Respiratory failure due to paralysis of the respiratory musculature can occur between several and up to 60 h after the bite.

Hyperkalaemia in the early stages of envenoming (myonecrosis) and acute renal failure somewhat later in the course of envenoming may also cause severe complications and death (Reid 1975b, 1979).

Cardiac effects

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Cardiac dysrhythmias (secondary, see above "Muscular effects") (Reid 1975b, 1979).

Renal effects

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Renal failure (secondary, see above "Muscular effects") (Reid 1975b, 1979).

Other signs & symptoms

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Nausea, vomiting, headache (Reid 1975b, 1979).

Morbidity

Without antivenom it can take several months for a patient who suffers severe envenoming to be restored to full health. In the first month after the bite the symptoms are similar to those of a muscular dystrophy. Later on the patient is able to make a firm fist and to raise themselves from a lying to a sitting position. Even after 1.5 years there may be mild residual muscle weakness. Irreversible damage of the skeletal musculature is possible, particularly if the muscles are used again too soon and the preserved sarcolemmal sheaths, which are crucial structures for muscle regeneration, are torn.

Renal failure (Reid 1975a, b).

Case fatality rate

7/55 patients who were bitten by E. schistosa according to the above-mentioned criteria.

At the time when no antivenom was available, mortality from sea snake bites was estimated at 10%. However, if only the cases of severe envenoming (see above for definition) are considered, around 50% (6/11) died in the pre-antivenom era. Once antivenom became available, 20% (2/10) of the patients with severe envenoming died, although these patients were already moribund upon arrival at hospital (Reid 1975a, b).

Laboratory and physical investigations

1. Leucocytes
Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Leucocytosis. In severe envenoming generally >20,000/mm³ (Reid 1975a, b).

2. Serum urea, creatinine
Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Elevated as a consequence of myonecrosis and acute renal insufficiency (Reid 1975a, b).

3. Serum potassium
Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Elevated as a consequence of myonecrosis and acute renal insufficiency (Reid 1975a, b).

4. AST (GOT), CPK

Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)

These enzymes are released from the damaged skeletal muscles and are very sensitive indicators of sea snake envenoming. Their levels do not correlate with the severity of envenoming.

Mild envenoming: serum AST significantly increased over 1–3 days (Reid 1975a, b).

Hydrophis cyanocinctus
CPK isoenzymes: 93,200 IU/l (MM 100%, MB 0%, BB 0%) (Higa et al. 1990).

5. Myoglobin
Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Detectable in serum and urine (Reid 1975a, b).

Hydrophis cyanocinctus
Serum myoglobin: 11,200 ng/ml (normal <70 ng/ml) (Higa et al. 1990).
Myoglobin in the urine: 660 ng/ml (normal <20 ng/ml) (Higa et al. 1990).

6. ECG
Enhydrina schistosa (Hydrophis cyanocinctus, Hydrophis spiralis)
Signs of hyperkalaemia (Reid 1975a, b).

7. EMG

Findings indicate a myopathy (Sitprija et al. 1971). The species of sea snake that caused both these accidents were not identified.

8. Muscle biopsy
E. schistosa

Histology: extensive hyaline necrosis. Individual muscle fibres may be affected while directly adjacent fibres remain undamaged. Within a single muscle fibre only one to a few segments are affected. There is usually an abrupt transition between damaged and undamaged segments within a single muscle fibre. The sarcolemma remains intact (Marsden and Reid 1961). The autopsied cases had all been bitten by E. schistosa according to the above-mentioned criteria.

9. Renal biopsy

Histology: acute tubular necrosis (Marsden and Reid 1961: the autopsied cases had all been bitten by E. schistosa according to the above-mentioned criteria; Sitprija et al. 1971: the species of sea snake that caused the accidents were not identified).

Treatment (symptomatic)

1. Immobilisation to guarantee undisturbed regeneration of the skeletal musculature.
2. Maintenance of sufficient hydration levels and diuresis. 
3. Lowering of increased serum potassium.
4. Endotracheal intubation, artificial respiration.
5. Dialysis. Besides the renal insufficiency, dialysis also improved the symptoms in the skeletal musculature (Sitprija et al. 1971: the species of sea snake that caused the accidents were not identified).
6. Neostigmine appears to be ineffective in the cases observed by Reid (1956, 1961b). Among the patients who received neostigmine (1.5 mg Prostigmin i.v.) there were some who had been bitten by E. schistosa according to the above-mentioned criteria. This supports the proposition that in cases of envenoming in humans caused by these sea snake species the effect of the venom on the skeletal musculature (myonecrosis) is foremost.

Treatment (specific)

Antivenoms
Sea snake antivenom (CSL, Parkville, Australia).
Tiger snake antivenom (CSL, Parkville, Australia).

Antivenom indications

Signs of effects of the venom on the skeletal musculature (see above "Signs and symptoms: Muscular effects" and "Laboratory and physical investigations"); leucocytosis (>20,000/mm³). Antivenom is not administered until clear systemic signs of envenoming develop, as in the great majority (approx. two thirds) of bites there is no injection of venom at all or only a small, clinically irrelevant amount, and the efficacy of the antivenom is guaranteed even after the onset of systemic symptoms of envenoming (see below) (Reid 1979).

Efficacy
Sea snake antivenom (CSL).

Pre-antivenom era: approx. 50% (6/11) of patients with severe envenoming (see above for definition) died.

Once antivenom became available only 20% (2/10) of patients with severe envenoming died, although these patients were already moribund upon arrival at hospital.

Antivenom has been observed to be effective up to 2 days after the bite.

Efficacy with regard to the effects of the venom on the skeletal musculature: the symptoms caused by the myotoxic effects of the venom disappear very quickly. Nonetheless it is necessary to continue to observe patients for several days with regard to hyperkalaemia and renal function (Reid 1975a, b).

Evaluation and recommendations

A comparison of 4 commercially available sea snake antivenoms in vivo and in vitro (Baxter and Gallichio 1974, 1976) reached the conclusion that all 4 antivenoms had good efficacy against the venom of 9 species of sea snake (Aipysurus laevis, Astrotia stokesii, Enhydrina schistosa, Hydrophis cyanocinctus, H. elegans, H. major, H. spiralis, Lapemis hardwickii, Laticauda semifasciata) as well as the Australian elapid species Notechis scutatus. According to these investigations the antivenoms are more effective the earlier they are administered. Nonetheless the clinical observations of Reid (1975b) showed that even the delayed use of antivenom is worthwhile and can clearly improve the patient's condition.

With regard to accidents in Australian waters the recommended choice is Sea snake antivenom (CSL) (Sutherland 1983, Williamson 1985).

Dose
Sea snake antivenom (CSL):
Initial dose 1,000 units (Acott 1983, Williamson 1985).
Tiger snake antivenom (CSL):
Initial dose 12,000 units (= 4 vials) (Acott 1983, Williamson 1985).