Clinic
Studies
South America
Brazil (Minas Gerais)
Crotalus durissus terrificus (and Crotalus durissus collilineatus)
Silveira and Nishioka 1992: 87 C. d. terrificus or C. d. collilineatus bites; identification: morphological: C. d. terrificus 6/87, C. d. collilineatus 5/87; according to clinical criteria and the patient's description (was only accepted if they clearly referred to the rattle on the end of the tail): 76/87. Retrospective study. The time between the bite and admission to hospital was 3 h (median; range 14 min–10 days). The time between the bite and antivenom administration is not known.
Brazil (São Paulo)
C. durissus terrificus
Cupo et al. 1988: 10 C. d. terrificus bites; identification: morphological 6/10, on the basis of information provided by relatives 4/10.
Classification:
- moderate envenoming 2/10: ptosis, impaired vision, dark urine;
- severe envenoming 8/10: in addition deterioration of the patient's general condition, generalised muscular pain, nausea, vomiting. 5 of 10 patients reached the hospital within ≤3 h, 3/10 within 3–6 h and 2/10 within >6 h. The time between the bite and antivenom administration is not known.
Cupo et al. 1990: 7 C. d. terrificus bites; identification: morphological 7/7. 1 of these 7 patients is identical to 1 of the 10 patients from Cupo et al. 1988.
Classification:
- moderate envenoming 1/7,
- severe envenoming 6/7.
5/7 reached the hospital within ≤3 h, 1/7 within 6 h and 1/7 within 24 h.
Central America
Costa Rica
C. durissus durissus (=Crotalus simus?)
Bolanos et al. 1981: 21 C. d. durissus bites; identification morphological.
Classification:
- only local signs of envenoming 11/21,
- local signs of envenoming (without necrosis) and mild systemic signs of envenoming 6/21,
- local signs of envenoming (with necrosis) and moderately severe systemic signs of envenoming 4/21.
Case reports
Brazil
C. durissus terrificus
Amorim and Mello 1952, 1954: 3 cases; identification morphological 1/3.
Regional differences in symptoms of envenoming due to C. durissus ssp.
In southern Brazil (C. d. terrificus) envenoming is characterised by paralysis, renal failure, a mild local reaction and a high mortality rate (the main component of the venom is crotoxin), while in Costa Rica it is characterised by local swelling, necrosis and a low mortality rate (paralysis and renal failure have not been reported to date); adult C. d. durissus do not have much crotoxin, while newborn animals have a lot. The symptoms of envenoming due to C. d. unicolor appear to be somewhere between those of C. d. terrificus and C. d. durissus (Hardy 1992a).
Signs & symptoms
Local effects
C. durissus terrificus
Strong pain immediately after the bite at the site of the bite. Frequently an absence of further local clinical signs (Rosenfeld 1971). Local signs 0/10 (Cupo et al. 1988), local erythema 3/7 (Cupo et al. 1990).
C. durissus durissus
Local pain and local swelling 11/21; strong local pain and local or extensive swelling with bleeding from the bite wound 6/21; very strong local pain, extensive swelling and necrosis in the region of the bite 4/21 (Bolanos et al. 1981).
Haemostatic effects
C. durissus terrificus
Conjunctival bleeding 1/87, gingival bleeding 1/87 (Silveira and Nishioka 1992), melaena and haematemesis 1/1 (Ekenbäck et al. 1985).
Generally only minor bleeding that was confined to the gingivae (Azevedo-Marques et al. 1990).
C. durissus durissus (=Crotalus simus?)
Minor systemic bleeding 4/21 (Bolanos et al. 1981).
Neurological effects
C. durissus terrificus (and C. d. collilineatus)
Preparalytic period: 30–60 min (Rosenfeld 1971).
"Neurotoxic facies" (Rosenfeld 1971) (blurred vision, ophthalmoplegia, ptosis) 39/64 (Silveira and Nishioka 1992).
Ptosis 10/10 (Cupo et al. 1988), 7/7 (Cupo et al. 1990), impaired vision 10/10 (Cupo et al. 1988), double images 7/7 (Cupo et al. 1990), mydriasis 9/10 (Cupo et al. 1988), 7/7 (Cupo et al. 1990).
Rarely dysphagia. Likewise paralysis of the extremities and disturbance of the respiratory musculature have only been described rarely (differential diagnosis: rhabdomyolysis) (Azevedo-Marques et al. 1990).
C. durissus durissus (=Crotalus simus?)
Neurological signs and symptoms 0/21 (Bolanos et al. 1981).
Muscular effects
C. durissus terrificus (and C. d. collilineatus)
Myalgia 25/87 (Silveira and Nishioka 1992), 9/10 (Cupo et al. 1988), 7/7 (Cupo et al. 1990).
C. durissus durissus (=Crotalus simus?)
0/21 (Bolanos et al. 1981).
Renal effects
C. durissus terrificus (and C. d. collilineatus)
Acute renal failure 13/87 (Silveira and Nishioka 1992). Chiefly a secondary effect due to rhabdomyolysis, along with other causes. There was a positive trend for acute renal failure with increasing age of the patients and the time between the bite and medical intervention. Myotoxic and neurotoxic signs of envenoming were only positively correlated with acute renal failure in patients >40 years (Silveira and Nishioka 1992).
Acute renal failure 2/10. These were the 2 children who only reached hospital 10 and 24 h after the bite (see also description of study above). One of the two (the one who reached hospital after 24 h) died on the 13th day after the bite (Cupo et al. 1988).
Acute renal failure 1/7. This was the child who only reached hospital 24 h after the bite (see also description of study above) (Cupo et al. 1990).
Acute renal failure 3/3 (Amorim and Mello 1952, 1954).
C. durissus durissus (=Crotalus simus?)
0/21 (Bolanos et al. 1981).
Other signs & symptoms
C. durissus terrificus
Vomiting 9/10 (Cupo et al. 1988), 2/7 (Cupo et al. 1990); sweating 8/10 (Cupo et al. 1988), 3/7 (Cupo et al. 1990); somnolence 10/10 (Cupo et al. 1988), 7/7 (Cupo et al. 1990).
Morbidity
Acute and chronic renal failure (see above).
Case fatality rate
C. durissus terrificus (and C. d. collilineatus)
The mortality rate for untreated cases is estimated to be over 70% (Rosenfeld 1971).
Acute renal failure is the most important complication after C. durissus bites and is most probably a highly significant factor determining the mortality rate in untreated patients.
2/15 patients who were treated in an intensive care unit for acute renal failure died (Da Silva et al. 1979) (however no details were given regarding the method used to identify the snakes that had caused the bites).
Antivenom treatment reduces the risk of death dramatically.
Mortality in patients treated with antivenom, 1/87 (Silveira and Nishioka 1992), 1/10 (this child only reached hospital 24 h after the bite and had developed acute renal failure) (Cupo et al. 1988) and 0/7 (Cupo et al. 1990).
3/3 as a result of renal failure (Amorim and Mello 1952, 1954).
C. durissus durissus (=Crotalus simus?)
0/21 (Bolanos et al. 1981).
Laboratory and physical investigations
1. Haemostasis
Type of haemostatic defect
C. durissus terrificus
Defibrin(ogen)ation (fibrinogen-coagulating activity via "thrombin-like" enzyme).
Platelet-activating activity that is obviously not clinically significant (Kamiguti and Cardoso 1989).
Haemostatic parameters
| Overview haemostasis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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H | CT | (FSP) | Tc | PT | aPTT | TT | I | FSP | D | II | V | VIII | X | XIII | PC | ATIII | PI | tPA | α2AP | |||||||||||||||||||||||||||||||||||||||||||
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E
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Essential bed-side tests |
Tests for full clinical assessment | Tests for research purposes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| A |
Haemorrhagins: According to clinical observations to date, haemorrhagin activity appears not to have any or at least only minor clinical significance (Kamiguti and Cardoso 1989). |
| B |
Clotting time: >15 min in 33/62 (Silveira and Nishioka 1992). Clotting time not measurable in 1/1 (Amaral et al. 1980). Incoagulable blood 9/29 (however no information regarding method used to identify the snakes!) (Kamiguti and Cardoso 1989). |
| C | aPTT, PT: C. durissus terrificus aPTT >180 s (normal <40 s ) 1/1 (Ekenbäck et al. 1985). PTT 180 s (normal 40–60 s) and PT not measurable (normal 12–14 s) 1/1 (Amaral et al. 1980). |
| D | Fibrinogen: C. durissus terrificus 0.1 g/l (normal 2–4 g/l) 1/1 (Ekenbäck et al. 1985). Plasma fibrinogen undetectable (normal 1.5–3.5 g/l) 1/1 (Amaral et al. 1980). Fibrinogen consumption and normal levels of factors II, V, VIII, IX, X, ATIII (Kamiguti, unpublished observations, cited in: Kamiguti and Cardoso 1989). C. durissus durissus*(=Crotalus simus?) Mild defibrinogenation 6/21; marked defibrinogenation 4/21 (Bolanos et al. 1981). |
| E |
Platelets: Thrombopaenia has not been observed to date (although the venom does contain a platelet-aggregating factor, but it is probably not present at sufficiently high levels) (Kamiguti and Cardoso 1989). |
2. Haemoglobin
C. durissus terrificus
Stable in 10/10 during observation over a period of 96 h after the bite (Cupo et al. 1988).
3. Myoglobin
C. durissus terrificus (and C. d. collilineatus)
Dark urine and/or positive urine dipstick test 35/87. Dark urine and/or positive urine dipstick test (haemoglobin) in the absence of erythrocytes in the urine sediment was considered an indirect indication of the presence of myoglobinuria in this study (Silveira and Nishioka 1992).
Dark urine 7/10, myoglobin in the urine 10/10, myoglobin in the serum 10/10. In patients in the early phase of envenoming who did not yet display raised levels of serum enzymes (CK, LDH, AST), myoglobin could already be detected in the urine and serum, even in those (3/10) whose urine was still pale. From 48–72 h after the bite, in those patients investigated, myoglobin was no longer detectable in the urine (Cupo et al. 1988).
Haemoglobin in the urine 0/10, haptoglobin in the normal range, i.e. no haemolysis (Cupo et al. 1988). First indication that C. durissus terrificus does not cause haemolysis, but rather rhabdomyolysis, in cases of human envenoming (Azevedo-Marques et al. 1985, 1987).
4. CK, LDH
C. durissus terrificus (and C. d. collilineatus)
- CK increased in 12/13 (max. 49,760 IU/l). The same patients also had raised serum concentrations of AST, LDH, CK/MB (Silveira and Nishioka 1992).
- CK increased in 10/10. Earliest indication of increased serum CK 1–3 h after the bite. Maximum CK level reached after 24 h (maximum 105,000 IU/l). LDH and AST likewise increased beyond the normal range, and LDH reached its maximum on approx. the 2nd–3rd day. If antivenom is administered early, CK, LDH and AST do not increase at all or only insignificantly (Cupo et al. 1988).
- Acute myocardial infarction-like CK, CK-MB, LDH (LDH1 fraction) enzyme constellation: early increase in CK with a parallel increase in the CK-MB fraction. Marked increase in CK values (>10,000 IU/l) as early as 3 h after the bite. Already starting to decrease again from the 2nd day after the bite. Slower increase in LDH (LDH1 fraction), with maximum values after 48–72 h and increased values over a period of several days (Cupo et al. 1990).
Clinical data, ECG and echocardiography do not support the interpretation of the enzyme constellation as a myocardial infarction enzyme pattern. The most likely interpretation is that C. durissus terrificus venom selectively damages type I and/or IIa skeletal muscle fibres, which are rich in the isoenzymes CK-MB and LDH1 and are thus similar to myocardial muscle fibres (Cupo et al. 1990).
5. Creatinine, urea, potassium
C. durissus terrificus
Increased in patients with acute renal failure (Azevedo-Marques et al. 1990).
6. Muscle biopsy
C. durissus terrificus
Necrotic muscle fibres alternating with intact fibres. Concurrent changes in the endothelial cell layer of intramuscular capillaries and small arterial vessels (Rossi et al. 1989).
7. Histological examination of the kidneys
C. durissus terrificus
Autopsy findings from 3 patients who died as a result of renal failure (Amorim and Mello 1952, 1954).
Treatment (symptomatic)
1. Dialysis
C. durissus terrificus (and C. d. collilineatus)
In 10/87, although 13/87 had developed acute renal failure (Silveira and Nishioka 1992).
Of 15 patients who were treated in an intensive care unit for acute renal failure, 9/15 were dialysed (1/9 died) and 6/15 were treated conservatively (1/6 died). In both of the deceased patients acute tubular necrosis was present (Da Silva et al. 1979; however no details were given regarding the method used to identify the snakes that had caused the bites).
2. Prevention of acute renal failure
C. durissus terrificus (and C. d. collilineatus)
Intravenous fluid supply, mannitol i.v., alkalinisation of the urine with sodium bicarbonate i.v. (Silveira and Nishioka 1992).
Treatment (specific)
Studies
No controlled clinical studies on dose determination and efficacy available.
Empirical data
C. durissus terrificus (and C. d. collilineatus)
87 patients received a dose of a specific Brazilian crotalid antivenom that is sufficient on average to neutralise 190 ± 95 mg of venom. 1/87 died, 13/87 developed acute renal failure (Silveira and Nishioka 1992).
C. durissus terrificus
10 patients (children) received specific Brazilian crotalid antivenom (Anticrotalic, Instituto Butantan, São Paulo, Brazil) i.v. For moderate envenoming, a dose of antivenom that is sufficient to neutralise 200–250 mg of venom is adequate, and for severe envenoming, a dose sufficient for ≥300 mg (see below, Evaluation and recommendations). 2/10 developed acute renal failure, 1/2 died on the 13th day after the bite, although peritoneal dialysis had been started in a timely manner. These two children were the last to reach the hospital (10 and 24 h after the bite), after they had received an inadequate dose of antivenom s.c. at the place where the bite had occurred. In 3 children who received specific antivenom within the first hour after the bite, the serum enzymes CK, LDH and AST did not increase at all or only insignificantly (Cupo et al. 1988).
C. durissus terrificus
7 patients (children) received specific Brazilian crotalid antivenom (Anticrotalic, Instituto Butantan, São Paulo, Brazil) i.v. at a dose sufficient to neutralise 200–300 mg of venom (see below, Evaluation and recommendations). 1/7 developed acute renal failure. This child only reached hospital after 24 h and first received antivenom at that time point. 5/7 received antivenom treatment after ≤3 h, 1/7 after 6 h (Cupo et al. 1990).
Evaluation and recommendations
C. durissus terrificus
The recommendations are not based on controlled clinical studies, as to date none have been conducted on the South American crotalid antivenoms. Empirically, the maximum amount of venom that can be milked from a snake of this species is still used as a guide. For severe cases of envenoming, the recommended initial antivenom dose is that which in animal experiments is able to neutralise the maximum amount of venom that can be milked from this species. For milder cases, the dose is calibrated accordingly (Rosenfeld 1971). With regard to neutralisation of the rhabdomyolytic activity of the antivenom, early administration appears to be crucial (Cupo et al. 1988).