Clinic
Studies
North America
Micrurus fulvius fulvius
1. Kitchens and Van Mierop 1987: 20 clearly identified M. fulvius fulvius bites. In 14 of 15 patients, the average time between the bite and appearance of the first symptoms of envenoming was 140 min (30–780 min!); the average time from the bite to clinical evaluation was 150 min (20–780 min).
Classification (at the time of the first clinical evaluation)
- no signs of envenoming 6/20
- local signs of envenoming 10/20
- systemic signs of envenoming 4/20.
Delay of 13 h between the bite and signs of severe systemic envenoming (complete paralysis, including the respiratory musculature) in one patient.
2. Parrish and Khan 1967: 6 clearly identified M. fulvius fulvius bites.
Grade 0: minimal local findings, no systemic signs of envenoming (3/6).
Grade I: local swelling and systemic signs of envenoming (nausea, vomiting, increased saliva production, paraesthesia of the bitten extremity, ptosis, muscle paralysis, dyspnoea, but no complete paralysis of the respiratory musculature during the first 36 h after the bite) (2/6).
Grade II: signs and symptoms as for grade I, but with complete respiratory paralysis within the first 36 h after the bite (1/6) (death due to respiratory failure).
Micrurus fulvius tenere (= M. tener)
Parrish and Khan 1967: 5 clearly identified M. fulvius tenere bites. No signs of envenoming.
Brazil
Micrurus lemniscatus
Casais e Silva and Brazil Nunes 1993: 7 M. lemniscatus bites; morphological identification.
Case reports
North America, USA
Micrurus sp.
Ramsey and Klickstein 1962: 1 case; morphological identification.
Micrurus fulvius
Moseley 1966: 1 case; morphological identification.
Micrurus fulvius fulvius
McCollough and Gennaro 1963: 1 case; morphological identification.
Micrurus fulvius tenere (= M. tener)
Norris and Dart 1989: 1 case; identification by geographical criteria.
Central America, Mexico
Micrurus laticollaris
Pettigrew and Glass 1985: 1 case; morphological identification.
South America, Brazil
Micrurus corallinus
Brazil 1980: 1 case; identification criteria not specified.
Columbia
Micrurus mipartitus
Mejia 1987: 3 cases; presumably morphological identification.
Signs & symptoms
Local effects
Micrurus fulvius
Bite marks 17/20, minor local swelling 8/20, minimal redness, local paraesthesia 7/20. Even in patients with severe systemic signs of paralysis, local signs are only mild (Kitchens and Van Mierop 1987).
Minimal local signs (Moseley 1966, McCollough and Gennaro 1963).
Micrurus laticollaris
Local swelling (Pettigrew and Glass 1985).
Micrurus lemniscatus
Local pain, erythema and local oedema 3/7 (Casais e Silva and Brazil Nunes 1993).
Neurological effects
Micrurus corallinus
Within hours, progressive paralysis sometimes extending to complete respiratory paralysis (Brazil 1980).
Micrurus fulvius
Diplopia 2/20, dyspnoea (paralysis of the respiratory musculature) 2/20, whereby 1 patient progressed to respiratory failure and required artificial respiration, muscle weakness 3/20, fasciculations 1/20 (Kitchens and Van Mierop 1987).
No cranial or peripheral neurological defects were determined in the first 15 h after the bite. Mild dyspnoea 22 h after the bite, ptosis, paralysis of the extremities and paralysis of the respiratory musculature with respiratory failure 31 h after the bite (Moseley 1966).
Appearance of neurological symptoms (ptosis, dyspnoea) 7.5 h after the bite, progressive paralysis of the cranial nerves, the limb musculature and the respiratory musculature, respiratory failure (McCollough and Gennaro 1963).
Appearance of neurological symptoms 2.5 h after the bite and respiratory failure within a few minutes (Ramsey and Klickstein 1962).
Micrurus laticollaris
Ptosis, dysarthria, difficulty chewing, weakness of the extremities, loss of taste within 24 h after the bite, maximum of 72 h after the bite (Pettigrew and Glass 1985).
Micrurus lemniscatus
Visual disturbances (2/7) (Casais e Silva and Brazil Nunes 1993).
Micrurus mipartitus
Progressive paralysis extending to tetraplegia 3/3 and complete respiratory paralysis 2/3 within 4–6 h (Mejia 1987).
Muscular effects
Pain on muscle palpation 2/20 (Kitchens and Van Mierop 1987).
Other signs & symptoms
Micrurus fulvius
Nausea 6/20, vomiting 5/20 (Kitchens and Van Mierop 1987). Often delayed appearance of systemic signs of envenoming (see above).
Micrurus laticollaris
Nausea (Pettigrew and Glass 1985).
Micrurus lemniscatus
Nausea and vomiting 1/7 (Casais e Silva and Brazil Nunes 1993).
Case fatality rate
Micrurus fulvius
0/20 (Kitchens and Van Mierop 1987). Respiratory failure as a result of paralysis of the respiratory musculature 1/6; the patient did not receive antivenom (Parrish and Khan 1967).
4/21, before Micrurus antivenom was available in the USA (Neill 1957).
No mortalities have been reported since the specific antivenom (Wyeth) became available (1967) (Norris and Dart 1989).
Cause of death respiratory failure due to paralysis of the respiratory musculature. Death occurred within 24 h (Willson 1908, McCollough and Gennaro 1970).
Micrurus lemniscatus
0/7 (Casais e Silva and Brazil Nunes 1993).
Micrurus mipartitus
0/3 (Mejia 1987).
Morbidity
Micrurus fulvius
Weakness of the skeletal musculature for several weeks after severe envenoming. No lasting sequelae (Kitchens and Van Mierop 1987).
Laboratory and physical investigations
1. Serum CK, LDH
Micrurus fulvius
CK maximum of 18,000 U/l in a patient with advanced signs of paralysis and generalised fasciculations (Kitchens and Van Mierop 1987).
Micrurus laticollaris
CK 1,392 U/l (normal 8–132 U/l); LDH 945 U/l (normal 83–200 U/l) (Pettigrew and Glass 1985).
2. EMG
Micrurus laticollaris
Repetitive stimulation of N. medianus: postsynaptic defect (Pettigrew and Glass 1985).
First aid
The compression-immobilisation method is recommended, based on its success in patients suffering from bites by Australian elapids (Norris and Dart 1989, Hardy 1992); however, the efficacy of this method for Micrurus bites has not yet been documented.
Treatment (symptomatic)
1. Respiratory insufficiency/respiratory failure
Micrurus fulvius
Endotracheal intubation is indicated at the first signs of bulbar paralysis (speech impairment, diplopia). 2/20 patients required endotracheal intubation due to bulbar paralysis despite receiving antivenom (Kitchens and Van Mierop 1987).
Micrurus mipartitus
Endotracheal intubation and ventilation successful in 2 patients (Mejia 1987).
Theoretically, acetylcholinesterase inhibitors could be of therapeutic benefit; however, as yet there are no studies on their use. The neurotoxic venom components are low-molecular polypeptides that cause a curare-like, postsynaptic, non-depolarising blockade at the neuromuscular end plates through competitive binding to the acetylcholine receptors. In contrast to curare, the blocking effect does not appear straight away and continues for a long time (Norris and Dart 1989). However, more recent findings show that different Micrurus species have different neurotoxic venom components: M. frontalis and M. lemniscatus (blockade of the motor end plates); M. corallinus (blockade of the motor end plates and presynaptic release of acetylcholine); M. fulvius and M. nigrocinctus (blockade of the motor end plates and depolarisation of muscle fibre membranes) (Brazil 1990).
2. Aspiration pneumonia
Micrurus fulvius
1/20 (Kitchens and Van Mierop 1987).
Prevention see 1. above.
Treatment (specific)
Studies
No controlled clinical studies on dose determination and efficacy.
Empirical data
Micrurus fulvius
Antivenom
Wyeth antivenom (Micrurus fulvius).
NB: This antivenom is not effective for Micruroides bites. However, all known cases of envenoming to date were so mild that the use of antivenom was not necessary.
17/20 received antivenom, most within 8 h and all within 12 h after the bite: 5/20 with advanced symptoms, 8/20 at the start of symptoms, 4/20 'prophylactically'. Average dose 6.5 vials (range 1–20 vials) (Kitchens and Van Mierop 1987).
Efficacy
No quick reversal of the symptoms of envenoming. In fact, symptoms might even progress (as far as respiratory paralysis) despite administration of antivenom.
Efficacy with regard to neurological signs of envenoming
Neurological symptoms may progress despite antivenom treatment in particular when neurotoxic signs were already evident at the start of treatment. It is not clear whether administration of antivenom can alter the duration of a complete paralysis if it was already present at the time of administration (Kitchens and Van Mierop 1987). 13/20 patients received antivenom due to local or systemic signs of envenoming; in 4 of these patients the symptoms progressed despite treatment, and 2 progressed to bulbar paralysis and had to be intubated (Kitchens and Van Mierop 1987).
Adverse reactions
Urticaria 6/17, anaphylactic shock 1/17. Serum sickness 2/17. If the chosen criteria for a diagnosis of serum sickness had been accelerated BSR, proteinuria and eosinophilia, the incidence would have been higher (Kitchens and Van Mierop 1987).
Antivenom indications
Micrurus fulvius (also valid for other Micrurus sp.)
- Neurotoxin-related signs and symptoms.
- Bite clearly identified to have been caused by M. fulvius, whereby the snake needs to have chewed during the bite, and blood can be exuded through the skin wounds caused by the bite (Kitchens and van Mierop 1987). The reasons for such liberal antivenom indications are the fact that with M. fulvius bites it is difficult to determine whether venom has been injected and because systemic signs of envenoming appear with a delay of more than 12 h, are difficult to reverse using the available antivenom and can even progress.
Recommended antivenom dose
Micrurus fulvius
Indication 1:
corresponding effect (Kitchens and Van Mierop 1987). 3–6 vials within 1–2 h as the initial dose, followed by 3–5 vials if new signs and symptoms appear or symptoms progress (Norris and Dart 1989).
Indication 2:
4–6 (10) vials within 4–8 h as the initial dose (Kitchens and Van Mierop 1987).
3–6 vials within 1–2 h as the initial dose, followed by 3–5 vials if signs and symptoms appear in spite of treatment (Norris and Dart 1989).