Clinic
Studies
Vipera berus, Vipera aspis
Audebert et al. 1992: 102 V. berus/V. aspis bites; identification: geographical criterion, ELISA.
Kaufmann 1892: 63 V. berus/V. aspis bites; identification: geographical criterion, in a few cases morphological.
Persson and Irestedt 1981: 136 V. berus bites; identification: geographical criterion.
Petitpierre 1934: 20 V. berus/V. aspis bites; identification: geographical criterion, in a few cases morphological.
Stahel et al. 1985: 113 V. berus/V.aspis bites; identification: geographical criterion, in a few cases morphological.
Reid 1976: 95 V. berus bites; identification: geographical criterion; review of cases from the previous 100 years.
Karlson-Stiber et al 2006: 231 V. berus bites; identification: geographical criterion.
Petite 2005: 99 V. aspis bites; identification: geographical criterion.
Grönlund et al 2003: 68 V. berus bites; identification: geographical criterion.
See also Table 4.13 "Variability of the clinical picture of envenoming due to European vipers (V. berus, V. aspis)”, see there for the study design.
With regard to the clinical data on envenoming (see below), symptoms, signs and laboratory results refer to the number of patients who showed oedema as a sign that venom was injected.
Case reports
V. berus
Morton 1960: 2 V. berus bites; identification: geographical criterion.
Arneil and Maclaurin 1961: 1 V. berus bite; identification: geographical criterion.
Brown and Dewar 1965: 1 V. berus bite; identification: morphological.
Chadha et al. 1968: 1 V. berus bite; identification: morphological.
Gerrard and Pugh 1982: 1 V. berus bite; identification: geographical criterion.
Jones and Clegg 1985: 1 V. berus bite; identification: geographical criterion.
Cederholm and Lennmaken 1987: 3 V. berus bites; identification: geographical criterion.
V. aspis
Antonini et al. 1991: 1 V. aspis bite; identification: morphological.
Beer and Putorti 1998: 2 V. aspis afrancisciredi bites; identification: georaphic criterion
Re et al 1999: 1 V. aspis bite; cited as "identified".
de Haro et al 1994: 2 V. aspis aspis bites, identification: georaphic criterion.
de Haro et al 2002: 5 V. aspis aspis bites and two already published V. aspis aspis bites (De Haro et al 1994), identification: georaphic criterion, immunological.
V. ammodytes
Jackson 1980: 1 V. ammodytes bite; identification: morphological.
European vipers
Aravanis et al. 1982: 1 bite due to a European viper; identification: geographical criterion.
Signs & symptoms
Autopharmacological effects
Gastrointestinal
Nausea, vomiting, diarrhoea, abdominal pain.
Gastrointestinal symptoms occurred in 55.6% of patients within the first hour, and in 83.3% within the first 2 h after the bite (Stahel et al. 1985, n = 36).
Cardiovascular
Sweating, pallor, cold extremities, tachycardia, arterial hypotension, shock; multifactorial: 1. direct vascular effects of the venom, 2. intravascular fluid loss (oedema), (3. haemoglobin decrease, 4. cardiac?).
Somnolence 8/100 (Stahel et al. 1985), confusion and somnolence 11/131 (Persson and Irestedt 1981).
Coma 3/100 (Stahel et al. 1985), 4/131 (Persson and Irestedt 1981), probably part of the shock symptoms (Reid 1976).
If the patient goes into shock, it will be within the first 2 h (Persson and Irestedt 1981), but there can be a longer latency period (Reid 1976).
Cardiovascular impairment within the first hour after the bite in 62.5%, within the first 2 h in 87.5% (Stahel et al. 1985, n = 32).
Audebert et al. 1992 distinguish between acute anaphylactic/anaphylactoid reactions to the venom (7/102), including anaphylactic shock (4 of the 7 patients with acute anaphylactic reactions), and hypotensive reactions due to another cause (17/82). 2 of these 17 developed severe shock, of whom one died. The occurrence of anaphylactic reactions does not appear to correlate with the severity of envenoming as defined by the classification of these authors (see below). Severe anaphylactic/anaphylactoid reactions were observed after the 2nd, 3rd and 4th bite, some of which were caused by European vipers. In most cases, sensitization was not caused by the same species that later caused the allergic reaction. It is assumed that there is cross-antigenicity (Schmutz and Stahel 1985).
Skin
Angioneurotic oedema (Schmutz and Stahel 1985).
Pulmonary
Dyspnoea (bronchospasm) (Persson and Irestedt 1981).
Local effects
Pain at the site of the bite
Remarkably rarely described in retrospective studies. In a prospective study (Audebert et al. 1992), however, 35/82 patients had local pain. Nonetheless, even with severe envenoming pain can be minimal or absent (Persson and Irestedt 1981).
Swelling
Oedema occurred in 82/102 prospectively studied bites (V. berus, V. aspis). In all 82 patients the oedema occurred within the first 2 h. All patients who developed no oedema or only local oedema also had no systemic signs of envenoming and had venom levels in blood/serum and urine that were no different from those in the control group (individuals not bitten). The extent of the oedema (regional oedema = majority of the bitten extremity affected, and extensive oedema = regional oedema and trunk affected) was a good indicator of systemic envenoming: sensitivity 100%, specificity 85%, positive predictive value 65%, negative predictive value 100% (Audebert et al. 1992). As the maximum extent of oedema cannot be predicted in the early stage of envenoming (in 2 patients, maximal oedema occurred 5 days after the bite!), this sign by itself is not a good parameter for evaluation of the severity of envenoming. In contrast, the speed at which oedema spreads appears to be a very reliable indicator.
Ecchymoses in the region of the oedema 44/100 (Stahel et al. 1985); 16/82 (Audebert et al. 1992).
Haemostatic effects
Systemic bleeding (Gerrard and Pugh 1982) is the exception even in cases of severe envenoming (Reid 1976) (see below, Haemostasis).
Neurological effects
Although neurotoxic phospholipases are present in the venom of European vipers, neurotoxic signs of envenoming, such as ptosis, ophthalmoplegia and paralysis of the skeletal musculature, are generally not observed. The reason for this is considered to be the small amounts of venom that are injected by European vipers (Mebs and Langelüddeke 1992). However, cases of envenoming due to V. aspis with neurological signs (predominately cranial nerve deficits, such as facial diplegia, pharyngo-laryngeal paralysis, bilateral ptosis and external ophthalmoplegia, dysphonia, dysphagia, but also dyspnoea) have been described in Italy (Antonini et al. 1991, Beer and Putorti 1998, Re et al 1999) and in South-Eastern France (de Haro et al 1994, 2002).
Muscular effects
Although myotoxins are present in the venom of European vipers, they generally do not cause any visible effects in humans. The reason for this is considered to be the small amounts of venom that are injected by European vipers (Mebs and Langelüddeke 1992).
Cardiac effects
Myocardial injury in connection with envenoming due to European vipers has been reported (see below, Laboratory and physical investigations, 4. ECG), but it is unclear to what extent it can be primarily (solely) attributed to the effects of toxins.
Renal effects
(Secondary) renal failure (see Laboratory and physical investigations, 5. Kidney function)
Table 4.12 Classification of V. berus and V. aspis bites and correlation with venom levels in blood or serum and urine (ELISA) (Audebert et al. 1992)
| Grade | Envenoming | Characterisation | Venom levels in blood or serum and urine |
| 0 | none |
bite marks no oedema |
= control group |
| 1 | minimal |
local oedema in the region of the bite no systemic signs of envenoming |
= control group |
| 2 | moderate |
regional oedema that affects the majority of the bitten extremity moderate systemic signs of envenoming (mild hypotension, vomiting, diarrhoea) |
statistically significantly > control group |
| 3 | severe | oedema that extends to the trunk severe systemic signs of envenoming (persistent hypotension, shock, bleeding) |
statistically significantly > control group |
Morbidity
136/5.2 million (5.2 million represents 63% of the Swedish population, who were registered in the central Diagnostic Code Register at the time of the investigation) were hospitalised in 1975 for a viper bite. 16/131 (12%) had a severe course of envenoming (grade D, see classification in Table 4.14) with an average hospital stay of 7.6 days. Children developed marked anaemia (Persson and Irestedt 1981). In the study of Stahel et al. 1985, severe envenoming was no more common in children than in adults. Myocardial infarction in connection with viper bites in isolated cases (Brown and Dewar 1965, Aravanis et al. 1982).
As long as the bitten extremity is not interfered with (by means of tourniquets, compression bandages, incisions and other inadvisable or contra-indicated interventions), necrosis hardly ever occurs. Complete recovery can take weeks or months, especially in adults, during which time swelling of the affected extremity may recur and ongoing pain can be very debilitating. In the (retrospective!) study of Reid (1976), two thirds of the patients were free of symptoms only after ≥3 weeks, and a quarter only after 1–9 months.
Case fatality rate
In Sweden, 44 deaths were recorded between 1911and 1978, and none since then (Persson and Irestedt 1981).
In Switzerland, from 1881–1930, 25 people died of bites from native venomous snakes (Petitpierre 1934); in the years from 1931 to 1965, in contrast, only 3 people died (1934, 1952 and 1960) (Hediger 1969, Kaufmann 1882).
In Great Britain, 14 deaths were recorded between 1876 and 1976 (Reid 1976). Comparison of fatalities due to V. berus bites and bee and wasp stings in England and Wales from 1950–1976 (Reid 1976): 1 fatality due to a bite from a native viper, 61 deaths due to bee or wasp stings.
See also Table 4.13.
Laboratory and physical investigations
1. Haemostasis
Type of haemostatic defect
European viper venoms do have haemorrhagic activity; however, due to the small amounts of venom injected in humans, the haemorrhagic activity does not take effect. The proteolytic activity is very slight compared to the haemorrhagic activity. This explains the infrequency of primary haemorrhagic complications (Calderon et al. 1993, Mebs and Langelüddeke 1992).
Haemostatic parameters
In 10/102 patients investigated in a prospective study, coagulation parameters were determined: low platelets (2/10) and decreased fibrinogen (3/10) with no clinical manifestations (Audebert et al. 1992). Mild decrease in platelets, the Quick value (PT) and fibrinogen without clinical manifestations in individual cases (Stahel et al. 1985).
2. Leucocytes
Leucocytosis in 46/131 (Persson and Irestedt 1981).
3. Haemoglobin/haematocrit
Haemoconcentration in severe cases. Reasons are extensive oedema, vomiting, diarrhoea. Anaemia (extravasation of erythrocytes and haemolysis) (primary/secondary?) (Persson and Irestedt 1981).
4. ECG
T wave inversion (Chadha et al. 1968), myocardial infarction patterns (Brown and Dewar 1965, Aravanis et al. 1982), repolarisation abnormalities in 3/5 cases, not accompanied by arterial hypotension or tachycardia (Stahel et al. 1985). Flat or negative T waves (3/131) (Persson and Irestedt 1981). Non-specific ECG changes (chiefly T wave inversion) in patients with mild and severe envenoming, but also normal ECG findings in patients with envenoming of all grades (Reid 1976).
5. Kidney function
Increase in serum creatinine, haematuria, proteinuria, oliguria and anuria were observed (Persson and Irestedt 1981). However, clinically relevant impairment of kidney function is rare and probably usually secondary (arterial hypotension).
6. ELISA
ELISA test (serum, urine) to supplement the clinical classification of the severity of envenoming:
The ELISA test employed by Audebert et al., when performed >2 h after the bite, allows prediction of the severity of envenoming. In a prospective study, the ELISA test distinguished clearly between patients with severe envenoming (grade 3) and the remaining patients and is thus a valuable aid in deciding whether antivenom is indicated (Audebert et al. 1992).
An ELISA test that detects V. ammodytes venom antigen within less than 20 min has been developed (Labrousse et al. 1988). A corresponding test for V. aspis, V. berus and V. ammodytes is in development (Audebert et al. 1992).
Treatment (symptomatic)
In most patients with mild hypotension (12/17), normal blood pressure could be restored with intravenous fluids (500 ml). In cases of severe hypotension, large amounts of intravenous fluids were required to restore normal blood pressure (5/17). 2 of these patients went into severe shock despite receiving >1,000 ml of fluids and dopamine; 1 of the 2 died (Audebert et al. 1992).
Efficacy of symptomatic treatment
9 patients with moderately severe envenoming (grade 3, see classification in Table 4.15) and 4 with severe envenoming (grade 4, see classification 4.15) (Stahel et al. 1985), 21 patients with moderate envenoming (grade C, see classification in Table 4.14) and 16 with severe envenoming (grade D, see classification in Table 4.14) (Persson and Irestedt 1981) did not receive antivenom and survived.
29 patients with moderate envenoming (grade 2, see classification in Table 4.12) and 5 patients with severe envenoming (grade 3, see classification in Table 4.12) did not receive antivenom. 1 of these 34 patients died (from the group with severe envenoming) (87-year-old woman, death due to shock, spontaneous bleeding with DIC, respiratory and kidney failure) (Audebert et al. 1992).
Treatment (specific)
Antivenoms
- "Antiviperinum", Institute of Immunology, Zagreb, Croatia
- Vipera berus antivenom, ovine, Fab, affinity purified, Therapeutic Antibodies Inc. (TAb)
- Purified equine F(ab')2 antivenom (Viperfav™)
- Schlangengift-Immunserum Europa, Behringwerke, Marburg, Germany
Efficacy of individual antivenoms
- "Antiviperinum", Institute of Immunology, Zagreb: Purified F(ab')2 fragments obtained from horses injected with V. ammodytes venom. High cross-reactivity with all European vipers. More effective against the individual venoms of the European viper species than the polyvalent antivenoms. Good efficacy in animal experiments (Theakston and Reid 1976).
In a comparison of 5 antivenoms (Stanic 1969), the Zagreb antivenom had the highest degrees of concentration and purity [in the study of Stanic 1969, the antivenom labelled with the code number 5 is the Zagreb antivenom (Stanic, pers. comm., cited in Theakson and Reid 1976)].
The antivenom has a very good reputation in clinical use in Great Britain and other European countries (Smith et al. 1992). - "Antiviperinum", Institute of Immunology, Zagreb, Croatia, or Schlangengift-Immunserum Europa, Behringwerke, Marburg, Germany: Retrospective study to evaluate the efficacy and rate of adverse reactions of 2 equine F(ab')-2 antivenoms.
Study group: 30 patients with envenoming due to V. berus bites who had received one of the two above-named antivenoms. Signs of envenoming: see the study of Persson et al. 1994 below. Control groups: 16 patients who displayed signs of envenoming of an equal degree but were not treated with antivenom, and 38 patients who had only mild signs of envenoming and for this reason were not treated with antivenom.
Findings: in the group that was treated with antivenom, the incidence of marked oedema (23 vs. 88%) and anaemia (10 vs. 50%) was significantly lower and the duration of hospitalisation shorter (median 3 vs. 6 days). In addition, antivenom treatment caused rapid improvement of acute symptoms of envenoming. However, adverse reactions, such as urticaria and serum sickness, occurred in 10% of the treated patients (Karlson-Stiber and Persson 1994). - Vipera berus antivenom, ovine, Fab, affinity purified, Therapeutic Antibodies Inc. (TAb): Open, multi-centre study in 18 Swedish hospitals between 1991and 1994 involving patients (N=30) with V.berus envenoming compered to historical controls. Antivenom dosing: first 4 trial patients: 100 mg of ovine Fab i.v. over 30 min, subsequent 19 patients 200 mg, 7 patients received repeated doses of 200 mg because of relapsing signs and symptoms or continued swelling. Inclusion criteria: (1) circulatory failure that does not respond well to symptomatic treatment or relapses, (2) persistent or recurrent gastrointestinal symptoms or (3) less pronounced circulatory problems or rapidly progressive local oedema combined with one of the following signs of envenoming, i.e. early, marked leucocytosis, marked haemolysis, coagulopathy, metabolic acidosis, or electrocardiographic abnormalities. The results were compared with those of 16 patients who had similar symptoms of envenoming but received no antivenom and with 30 patients who were treated with 1.4 g of equine F(ab')2 antivenom ("Antiviperinum", Institute of Immunology, Zagreb). Indications for antivenom treatment (ovine Fab antivenom) (see also inclusion criteria), time of antivenom application and clinical course:
-
- Group 1 (n=8): Indication: circulatory shock that responded poorly to symptomatic treatment or relapsed; time of antivenom application: 2.5 h (median) after the bite; clinical course: normal circulation restored the latest 30 min after antivenom infusion completed, 2 patients received a second dose (one patient with impaired oxygenation, dyspnoe, generalized oedema with a good response to the second dose; one patient with continued swelling);
- Group 2 (n=17): Vomiting, diarrhoea and abdominal pain lasting longer than 2 hours; time of antivenom application: 4 h (median) after the bite; clinical course: recovery time for gastrointestinal signs and symptoms 30 min to 2 h, angiooedema, circulatory instability and somnolence resolved more quickly; second antivenom dose: relapsing gastrointestinal signs and symptoms (2 patients), continued swelling (3 patients);
- Group 3 (n=5): leucocytosis (19.5 to 26.1x109/l) (n=5/5), T-wave in version in ECG (n=2/5), bite in lower lip with rapidly spreading local swelling and respiratory distress (n=1/5); time of antivenom application: >7 - 24 h (only patient with bite in lip 2.5. h); clinical course: response of local effects difficult to assess, criculatory instability prompt response.
Comparison between patients treated with antivenom (equine F(ab')2 antivenom or ovine Fab antivenom) and untreated patients:
- Extensive oedema (swelling extending beyond the bitten limb) in severe envenoming observed in 88 % of non-treated and 23 % of treated patients.
- Anaemia (≥10% below the lowest normal value) 44 % of non-treated and 10 % of equine F(ab')2 antivenom and 23% of ovine Fab antivenom treated patients.
- Time in hospital: in both treated groups lower than in not treated group.
- Acute or delayed antivnom reactions: 10 % in equine F(ab')2 antivenom and non in ovine Fab antivenom treated patients.
Conclusion: Ovine Fab antivenom is safe and effective. For the majority of patients an initial dose of 200 mg can be recommended to be repeated if recrudescence of systemic signs and symptoms or continued swelling occurs (Karlson-Stiber et al 1997).
- Purified equine F(ab')2 antivenom (Viperfav™): Open, multicentre clinical trial (N=46); moderate to severe envenoming (grade 2 and 3; see Table 4.16 below). Initial dose: 1 dose; if needed 4 additional doses at 4-hour intervals. Results: Severity grade decreased by at least 1 grade in 35 patients. In 2 patients (grade 3) the effect of the antivenom was assessed as "inefficient" by the investigators (de haro et al 1998).
- Purified equine F(ab')2 antivenom (Viperfav™): Retrospective case review in two French poison centers. Of 207 cases of European viper bites of which 119 were grade 2 or 3 (see Table 4.16 below) the treated group 1 (n=48) (Viperafav™) and the unreated group 2 (n=71) were compared. Comparison of the two groups before treatment showed no significant differences. Comparison of the clinical evolution of the two groups: Complications (renal, pulmonary, haemorrhage): 4% group 1, 21% group 2; sequelae: 0% group 1, 14% group 2; ICU > 3 days: 0% group 1, 28% group 2, total hospital stay: 3.3 days group 1, 8.7 days group 2 (Harry et al 1999).
- Purified equine F(ab')2 antivenom (Viperfav™): 5 patients with neurotoxic signs and symptoms in South-Eastern France responded favouably to this antivenom (de Haro et 2002).
Adverse reactions to antivenoms
- "Antiviperinum", Institute of Immunology, Zagreb: Although this antivenom does not contain any immunoglobulin Fc fragments, which are considered responsible for allergic reactions, adverse reactions occur in 6–7% of treated patients (Karlson-Stiber et al. 1990, cited in: Smith et al. 1992). Nonetheless, with the exception of TAb antivenom, severe antivenom reactions in particular are much less likely with Zagreb antivenom in comparison to all other antivenoms against European vipers.
- Vipera berus antivenom, ovine, Fab, affinity purified, Therapeutic Antibodies Inc. (TAb): None of the 30 patients who have received this antivenom had adverse reactions (Karlson-Stiber et al 1997). In analogy to digoxin-specific antibodies (Digibind®), a product that is produced in the same way as the TAb Vipera berus antivenom, a rate of allergic adverse reactions of less than 1% is to be expected, and none of the reactions should take a severe course (Smith et al. 1992).
Antivenom indications
- Drop in blood pressure (systolic to <80 mmHg or around >50 mmHg compared to the systolic blood pressure at the initial investigation) with or without signs of shock (Warrell 2005, 2010).
- Signs of systemic envenoming, such as spontaneous bleeding, coagulopathy, pulmonary oedema or pulmonary haemorrhage (chest X-ray), ECG abnormalities, leucocytosis and elevated serum creatin kinase (Warrell 2005, 2010).
- Severe local signs of envenoming, even in the absence of systemic signs of envenoming: swelling that involves >1/2 of the affected extremity within 48 h, or rapidly spreading local swelling that reaches the forearm or lower leg within about 4 h of the bite (Warrell 2005, 2010).
- Cranial nerve deficits, such as facial diplegia, pharyngo-laryngeal paralysis, bilateral ptosis and external ophthalmoplegia, dysphonia, dysphagia, paraysis of skeletal muscles may be an additional indication given the experince e.g. in Souh-Eastern France (de Harro et al 2002)
Recommendation
To prevent morbidity and reduce length of convalescence in patients with moderately severe and to save lifes of severely envenomed patients equine F(ab')2 antivenom (Zagreb) or ovine Fab antivenom (Protherics ViperaTAb) are recommended (Warrell 2010).
Efficacy (general)
- With regard to autopharmacological effects of the venom: no controlled clinical studies are available. Allergic reactions, in particular IgE-mediated reactions, are not influenced by antivenom. Complex autopharmacological effects of toxins, in particular arterial hypotension and shock, appear to respond to antivenom, according to individual observations, and represent an indication for administration of antivenom (Reid 1976, Warrell 2010).
- With regard to local effects of the venom: European viper bites very rarely cause necrosis, as long as no contra-indicated first aid or medical interventions have been employed (see above "Morbidity" and Table 4.13). The use of antivenom due to local effects of the venom can only be justified on the basis that it might decrease the period during which pain and recurrent swelling may occur, in particular in adults (see "Morbidity"). However, there are no controlled clinical studies on this subject. The recommendation to administer antivenom to adult patients who display swelling of the forearm or leg within 2 h after the bite is based on animal experiments. A clear effect of antivenom (Zagreb) on regional swelling and bleeding has been shown, as long as it was administered shortly after the bite (1 h) (Theakston and Reid 1976).
- Influence on duration of hospitalisation: in cases of severe envenoming (grade 4, see classification in Table 4.15) the duration of hospitalisation was decreased by half with administration of antivenom (mean stay without antivenom 10 days, with antivenom 5 days), in cases of moderately severe envenoming (grade 3, see classification in Table 4.15) it was not altered and in cases of no or mild envenoming (grade 2, see classification in Table 4.15) it was even prolonged (Stahel et al. 1985).
Table 4.13 Variability of the clinical picture of envenoming due to European vipers (V. berus, V. aspis)
| Country | Author |
n1 |
Study description |
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
| Sweden (V. berus) |
Persson and Irestedt 1981 | 131 | (1) | ND |
ND |
ND |
|||||||
| Switzerland (V. berus, V. aspis) |
Stahel et al. 1985 | 100 | (2) | ND |
49% | ||||||||
| France (V. berus, V. aspis) |
Audebert et al. 1992 | 82 | (3) | ND |
1.2% |
|
ND = Not determined. |
1 Patients definitely injected with venom (criterion: local oedema).
reactions to the venom (7/82 bites), including anaphylactic shock (4 of the 7 patients with acute anaphylactic reactions), and hypotensive reactions due to another cause (17/82). 2 ofthese 17 developed severe shock, of whom one died. |
|
Study descriptions
1. Persson and Irestedt 1981 (V. berus): retrospective study. Included all patients hospitalised due to bites from native snakes in Sweden in the year 1975 who had been recorded in the central Diagnostic Code Register (n = 136). The study thus allows an estimation of the incidence of cases of severe envenoming but not the incidence of snakebites in Sweden.
Table 4.14 Classification of Persson and Irestedt 1981 (slightly modified version of that of Reid 1976)
| Grade | Envenoming with |
Characterisation | n |
| A | minimal (or no) reaction | local swelling; no general symptoms apart from anxiety | 37 |
| B | slight reaction |
local or extensive swelling ± gastrointestinal symptoms, but no other systemic signs |
62 |
| C | moderate reaction | extensive oedema, shock <2 h, other signs of moderately severe systemic envenoming | 21 |
| D | severe reaction | shock >2 h or recurrent symptoms of shock; other signs of severe systemic envenoming | 16 |
| E | fatal outcome |
0 |
2. Stahel et al. 1985 (V. berus, V. aspis): retrospective study of bites from native snakes in Switzerland occurring over a period of 16 years (1967–1983). Sources: case collections of the Swiss Toxicological Information Centre, the Swiss Tropical Institute and the Upper Engadin County Hospital in Samedan, as well as individual cases from hospitals in the Jura region, Vaud, central Switzerland, the cantons Grisons and Ticino and terrarium owners who had been bitten.
Table 4.15 Classification of Stahel et al. 1985 (based on Reid 1976 and Gonzalez and Boada 1981)
| Grade | Envenoming | Characterisation | n |
| 1 | none | no local swelling 1 h after the bite | 13 |
| 2 | mild | one of the following as an isolated symptom: local swelling, tachycardia, hypotension, nausea or vomiting | 62 |
| 3 | moderately severe |
local or extensive swelling; two or more systemic symptoms such as diarrhoea, vomiting, abdominal pain, hypotension; no circulatory shock | 24 |
| 4 | severe |
local or extensive swelling; signs of systemic envenoming with circulatory shock and/or oropharyngeal angio-oedema |
14 |
3. Audebert et al. 1992 (V. berus, V. aspis): prospective, multi-centre study, large hospitals and toxicological information centres in France in regions with a high probability of viper bites, May to September 1990. ELISA investigations of blood or serum and urine samples collected during the first 12 h of hospitalisation. Calculation of the mean venom concentrations in serum and urine.
Table 4.16 Classification of Audebert et al. 1992
| Grade | Envenoming | Characterisation | Venom concentration in blood or serum and urine | n |
| 0 | none | bite marks, no oedema | = control group |
20 |
| 1 | minimal |
local oedema in the region of the bite, no systemic signs of envenoming |
= control group |
48 |
| 2 | moderate |
regional oedema affecting the majority of the bitten extremity; moderately severe systemic signs of envenoming (mild hypotension, vomiting, diarrhoea) |
statistically significantly > control group |
29 |
| 3 |
severe |
oedema extending to the trunk; severe systemic signs of envenoming (persistent hypotension, shock, bleeding) |
statistically significantly > control group |
5 |