Clinic: Vipera sp., European vipers

Examine for venom effects

Autopharmacological effects

• Nausea, vomiting
• Sweating
• Urticaria, angiooedema
• Arterial hypotension / hypovolaemic shock (transient, recurrent; immediate; delayed (CLS))
• Diarrhoea
• Bronchospasm 

Local Effects

• Pain
• Tender local (spreading) swelling
• Blistering
• Lymphangiopathy and lymphadenopathy
• Necrotic skin

Haematological effects 

• Clotting disturbances:
  • Bleeding from the fang marks and from injuries, in particular ones that are not located in the region in which venom application occurred.
  • Bleeding into the skin (ecchymosis, petechiae)
  • Gingival bleeding, bleeding from the nose, conjunctiva, haematemeis, bleeding per rectum, including melaena, haematuria, haemoptysis.
  • Oliguria, anuria (VICC / AKI)
• Bleeding and/or haemolytic anaemia:
  • Arterial hypotension (haemorrhagic shock)
  • Acute abdomen (intra-abdominal bleeding!)
  • Loin pain/renal bed sensitive to percussion (ischaemia, renal haemorrhage!)
  • Local neurological signs, meningism, coma (intracranial bleeding!)
  • Pale sclera
  • Oliguria, anuria (arterial hypotension / AKI)

Neurological effects

• Descending flaccid paralysis (rarely progresses to involve bulbar and respiratory muscles)
  • Ptosis (not to be mixed up with tiredness / drowsiness; test: lid retraction with upward gaze).
  • Double vision (external ophthalmoplegia)
  • Difficulties to swallow (dysphagia) (bulbar paralysis) > inhalation of vomitus!
  • Difficulties to lift the head when lying on the back (‘broken neck syndrome’)
  • Cyanosis, shallow breathing, respiratory arrest (respiratory paralysis); respiratory arrest may be precipitated by obstruction of the upper airway by the paralysed tongue or inhaled vomitus. 
  • Weakness or loss of voluntary movement; movements of digits may still be possible, allowing the patient to communicate.
  • Loss of consciousness and generalized convulsions caused by hypoxaemia in patients who have respiratory paralysis.  

(Cardiac Effects)

• Bradycardia, tachycardia, arrhythmias
• Arterial hypotension
• Heart failure
• ECG: Tachyarrhythmias, sinus bradycardia, ST-T wave changes, varying degrees of atrioventricular block, and evidence of hyperkalaemia.

Species-specific envenoming pattern

The assessment of the envenoming pattern is based on the data from publication in which the identification of the snakes is clearly specified and in accordance with accepted criteria.

Overview: envenoming pattern of Vipera berus and Vipera aspis

Variability of the clinical picture of envenoming due to European vipers (V. berus, V. aspis)

(Review: T. Junghanss)

 Classification of Persson and Irestedt 1981 (slightly modified version of that of Reid 1976)

Classification of Stahel et al. 1985 (based on Reid 1976 and Gonzalez and Boada 1981)

Classification of Audebert et al. 1992

Study descriptions

• 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.
• 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.
• 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.

¹Autopharmacological effects
Nausea, vomiting, diarrhoea, abdominal pain, incontinence of urine and faeces. Angioneurotic oedemaof the face, lips, gums, tongue, throat, and epiglottis; urticaria; and bronchospasm (Schmutz and Stahel 1985, Warrell 2005).
Sweating, pallor, cold extremities, tachycardia, arterial hypotension, loss of consciousness, shock; multifactorial: 1. direct vascular effects of the venom, 2. intravascular fluid loss (oedema), (3. haemoglobin decrease, 4. cardiac?).
If the patient goes into shock, it can be within 5 minutes (Warrell 2005), but there can be a longer latency period, and the signs and symptomsmay persist or fluctuate for as long as 48 hours in the absence of treatment. (Warrell 2005, Reid 1976).

²Local effect
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 (Audebert et al. 1992, Stahel et al. 1985).
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.

Hematological effects
³Bleeding
Systemic bleeding
Systemic bleeding (Gerrard and Pugh 1982) is the exception even in cases of severe envenoming (Reid 1976).
Clinical features of a bleeding diathesis are unusual, but bleeding from the gums and nose and into the lungs, gastrointestinal and genitourinary tracts, and serosal cavities and retroperitoneally can occur (Warrell 2005).
⁴Coagulopathy
Type of haemostatic defect
Venom-Induced Consumption Coagulopathy
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).
“Disorders of coagulation were rare in our series. Fibrinogen, measured in 49 cases, was abnormal in only 2 cases (number 2 and one case with grade 3: 1,85 g/l). In other patients with severe envenomation, fibrinogen was minimally and transiently decreased, often during the period of haemorrhage. PT and PTT were measured several times for 75 patients. A true disseminated intravas cular coagulopathy (DIVC) was diagnosed in 2 cases (numbers 2 and 3), accompanied by thrombocytopenia and hypofibrinogenaemia. In other 3 patients with grade 3, PT was abnormal at the admission. In all other patients with severe envenomation, changes of PT and PTT were minimal, and not correlated with thrombocytopenia.” (Petite 2005).

⁵Neurological effects
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 2002).

Other effects

Cardial effects

Myocardial injury in connection with envenoming due to European vipers has been reported.

Renal effects

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). 

Species-specific publications 
see ‘References’ at the end of the file.

Clinical management

See also Clinical Management: European vipers

for advice on post-First Aid measures, diagnosis (clinical, laboratory) and treatment (supportive, antivenom).

First Aid

Any type of tourniquet follow link above.

Local treatment

Pain control
Tetanus prophylaxis
Standard wound care
Necrosis: debridement
Systemic antibiotics: standard indications
WHO (2010) 

Systemic supportive treatment

A general understanding of emergency medicine is required, or can be found in emergency medicine guidelines, e.g. ABCDE approach, WHO-ICRC Basic Emergency Care.

Follow SAMPLE & ABCDE ApproAch

• Comprehensive ABCDE approach

• ICRC Basic Emergency Care: approach to the acutely ill and injured (SAMPLE  and ABCDE approach: first module) 

Obey european viper - specific features

see

• 'Species-specific envenoming pattern above'.

Key issues:

Rapid cardiovascular collapse, arterial hypotension, shock

If the patient goes into shock, it can be within 5 minutes (Warrell 2005), but there can be a longer latency period, and the signs and symptomsmay persist or fluctuate for as long as 48 hours in the absence of treatment. (Warrell 2005, Reid 1976).
See footnote 1 

Venom-induced coagulopathy (VICC) and bleeding

See footnotes 3 and 4

Neurological signs & symptoms

See footnote 5

Specific treatment (antivenoms)

• WHO Snakebite Information and Data Platform

References

• Antonini G, Rasura M, Conti G, Mattia C. Neuromuscular paralysis in vipera aspis envenomation: pathogenetic mechanisms. J Neurol Neurosurg Psychiatry. 1991 Feb;54(2):187. PMID: 2019852; PMCID: PMC1014365. https://doi.org/10.1136/jnnp.54.2.187

• Audebert F, Sorkine M, Bon C. Envenoming by viper bites in France: clinical gradation and biological quantification by ELISA. Toxicon. 1992 May-Jun;30(5-6):599-609. PMID: 1519251.

  https://doi.org/10.1016/0041-0101(92)90854-x
• Beer E, Putorti F. Dysphonia, an uncommon symptom of systemic neurotoxic envenomation by Vipera aspis bite. Report of two cases. Toxicon. 1998 May;36(5):697-701. PMID: 9655630. https://doi.org/10.1016/s0041-0101(97)00168-2
• Boels D, Hamel JF, Le Roux G, Labadie M, Paret N, Delcourt N, Langrand J, Puskarczyk E, Nisse P, Sinno-Tellier S, de Haro L. Snake bites by European vipers in Mainland France in 2017-2018: comparison of two antivenoms Viperfav^® and Viperatab^®. Clin Toxicol (Phila). 2020 Nov;58(11):1050-1057. Epub 2020 Mar 5. PMID: 32134691. https://doi.org/10.1080/15563650.2020.1726377
• de Haro L, Robbe-Vincent A, Saliou B, Valli M, Bon C, Choumet V. Unusual neurotoxic envenomations by Vipera aspis aspis snakes in France. Hum Exp Toxicol. 2002 Mar;21(3):137-45. PMID: 12102539. https://doi.org/10.1191/0960327102ht226oa
• Di NicolaMR, Pontara A, Kass GEN, Kramer NI, Avella I, Pampena R, Mercuri SR, Dorne JLCM, Paolino G. Vipers of Major clinical relevance in Europe: Taxonomy, venom composition, toxicology and clinical management of human bites. Toxicology. 2021 Apr 15;453:152724. doi: 10.1016/j.tox.2021.152724. Epub 2021 Feb 18. PMID: 33610611. https://doi.org/10.1016/j.tox.2021.152724
• Di Nicola MR, Crevani M, Avella I, Cerullo A, Dorne JCM, Paolino G, Zattera C. A Guide to the Clinical Management of Vipera Snakebite in Italy.Toxins (Basel). 2024 May 31;16(6):255. PMID: 38922149; PMCID: PMC11209566. https://doi.org/10.3390/toxins16060255
• Fuchs J, Gessner T, Kupferschmidt H, Weiler S. Indigenous venomous snakebites in Switzerland: analysis of reports to the National Poisons Information Centre over 22 years. Swiss Med Wkly. 2021 Dec 16;151:w30085. PMID: 34964582. https://doi.org/10.4414/smw.2021.w30085
• Gerrard M, Pugh R. An adder bite with unusual consequences. Practitioner 1982;226:527-8
• Karlson-Stiber C, Salmonson H, Persson H. A nationwide study of Vipera berus bites during one year-epidemiology and morbidity of 231 cases. Clin Toxicol (Phila). 2006;44(1):25-30. PMID: 16496490. https://doi.org/10.1080/15563650500394597
• Lamb T, Stewart D, Warrell DA, Lalloo DG, Jagpal P, Jones D, Thanacoody R, Gray LA, Eddleston M. Moderate-to-severe Vipera berus envenoming requiring ViperaTAb antivenom therapy in the UK. Clin Toxicol (Phila). 2021 Nov;59(11):992-1001. Epub 2021 Mar 15. PMID: 33720783. https://doi.org/10.1080/15563650.2021.1891245
• Persson H, Irestedt B. A study of 136 cases of adder bite treated in Swedish hospitals during one year. Acta Med Scand. 1981;210(6):433-9. doi: 10.1111/j.0954-6820.1981.tb09845.x. PMID: 7331888. https://doi.org/10.1111/j.0954-6820.1981.tb09845.x
• Petite J. Viper bites: treat or ignore? Review of a series of 99 patients bitten by Vipera aspis in an alpine Swiss area. Swiss Med Wkly. 2005 Oct 15;135(41-42):618-25. PMID: 16380847. https://doi.org/10.4414/smw.2005.11198
• Re G, Trisolino G, Miglio F. Eye muscle paralysis after Vipera aspis envenomation. J Accid Emerg Med. 1999 Nov;16(6):458. PMID: 10572830; PMCID: PMC1343423. https://doi.org/10.1136/emj.16.6.458
• Reid HA. Adder bites in Britain. Br Med J. 1976 Jul 17;2(6028):153-6. PMID: 1276841; PMCID: PMC1687390. https://doi.org/10.1136/bmj.2.6028.153
• Stahel E, Wellauer R, Freyvogel TA. Vergiftungen durch einheimische Vipern (Vipera berus und Vipera aspis).Eine retrospektive Studie an 113 Patienten [Poisoning by domestic vipers (Vipera berus and Vipera aspis). A retrospective study of 113 patients]. Schweiz Med Wochenschr. 1985 Jun 29;115(26):890-6. German. PMID: 4023676.
• Warrell DA. Treatment of bites by adders and exotic venomous snakes. BMJ. 2005 Nov 26;331(7527):1244-7. Erratum in: BMJ. 2006 Jan 21;332(7534):151. PMID: 16308385; PMCID: PMC1289323. https://doi.org/10.1136/bmj.331.7527.1244
• Warrell DA, Williams DJ. Clinical aspects of snakebite envenoming and its treatment in low-resource settings. Lancet. 2023 Apr 22;401(10385):1382-1398. PMID: 36931290. https://doi.org/10.1016/s0140-6736(23)00002-8
• WHO ABCDE Approach. https://cdn.who.int/media/docs/default-source/integrated-health-services-(ihs)/csy/bec-quick-cards/becp-edu29-pdf-en-finl.pdf?sfvrsn=2532d61b_2
• WHO-ICRC Basic Emergency Care: approach to the acutely ill and injured. https://www.who.int/publications-detail-redirect/basic-emergency-care-approach-to-the-acutely-ill-and-injured. https://cdn.who.int/media/docs/default-source/integrated-health-services-(ihs)/csy/bec-quick-cards/becp-edu29-pdf-en-finl.pdf?sfvrsn=2532d61b_2
• WHO Snakebite Information and Data Platform. https://www.who.int/teams/control-of-neglected-tropical-diseases/snakebite-envenoming/snakebite-information-and-data-platform
• WHO (2010) Wound and lymphoedema management. WHO/HTM/NTD/GBUI/20101 I. 2010. https://www.who.int/publications/i/item/9789241599139

Species-specific evidence

Vipera ammodytes

• Jackson OF. Effects of a bite by a sand viper (Vipera ammodytes). Lancet. 1980 Sep 27;2(8196):686-7. PMID: 6106795. https://doi.org/10.1016/s0140-6736(80)92718-x

Vipera aspis

Italy

• Antonini G, Rasura M, Conti G, Mattia C. Neuromuscular paralysis in vipera aspis envenomation: pathogenetic mechanisms. J Neurol Neurosurg Psychiatry. 1991 Feb;54(2):187. PMID: 2019852; PMCID: PMC1014365. https://doi.org/10.1136/jnnp.54.2.187
• Beer E, Putorti F. Dysphonia, an uncommon symptom of systemic neurotoxic envenomation by Vipera aspis bite. Report of two cases. Toxicon. 1998 May;36(5):697-701. PMID: 9655630. https://doi.org/10.1016/s0041-0101(97)00168-2
• Re G, Trisolino G, Miglio F. Eye muscle paralysis after Vipera aspis envenomation. J Accid Emerg Med. 1999 Nov;16(6):458. PMID: 10572830; PMCID: PMC1343423. https://doi.org/10.1136/emj.16.6.458
• Sassoè M. Envenomation by Vipera aspis in Piedmont (Italy): A report of three cases, including one case with neurological symptoms. Toxicon. 2023 Jul;230:107154. Epub 2023 May 9. PMID: 37169267. https://doi.org/10.1016/j.toxicon.2023.107154

France

• Audebert F, Sorkine M, Bon C. Envenoming by viper bites in France: clinical gradation and biological quantification by ELISA. Toxicon. 1992 May-Jun;30(5-6):599-609. PMID: 1519251. https://doi.org/10.1016/0041-0101(92)90854-x
• Boels D, Hamel JF, Le Roux G, Labadie M, Paret N, Delcourt N, Langrand J, Puskarczyk E, Nisse P, Sinno-Tellier S, de Haro L. Snake bites by European vipers in Mainland France in 2017-2018: comparison of two antivenoms Viperfav^® and Viperatab^®. Clin Toxicol (Phila). 2020 Nov;58(11):1050-1057. Epub 2020 Mar 5. PMID: 32134691. https://doi.org/10.1080/15563650.2020.1726377
• de Haro L, Robbe-Vincent A, Saliou B, Valli M, Bon C, Choumet V. Unusual neurotoxic envenomations by Vipera aspis aspis snakes in France. Hum Exp Toxicol. 2002 Mar;21(3):137-45. PMID: 12102539. https://doi.org/10.1191/0960327102ht226oa
• Ferquel E, de Haro L, Jan V, Guillemin I, Jourdain S, Teynié A, d'Alayer J, Choumet V. Reappraisal of Vipera aspis venom neurotoxicity. PLoS One. 2007 Nov 21;2(11):e1194PMID: 18030329; PMCID: PMC2065900. https://doi.org/10.1371/journal.pone.0001194

Switzerland

• Fuchs J, Gessner T, Kupferschmidt H, Weiler S. Indigenous venomous snakebites in Switzerland: analysis of reports to the National Poisons Information Centre over 22 years. Swiss Med Wkly. 2021 Dec 16;151:w30085. PMID: 34964582. https://doi.org/10.4414/smw.2021.w30085

Vipera berus

Finland

• Grönlund J, Vuori A, Nieminen S. Adder bites. A report of 68 cases. Scand J Surg. 2003;92(2):171-4. PMID: 12841560. https://doi.org/10.1177/145749690309200211
• Nurminen I, Eskola V. Most adder bites in Finland's Lake District caused mild symptoms and severe poisoning was rare. Acta Paediatr. 2022 Aug;111(8):1638-1643. Epub 2022 Jun 1. PMID: 35531612; PMCID: PMC9546192. https://doi.org/10.1111/apa.16397

France

• Boels D, Hamel JF, Le Roux G, Labadie M, Paret N, Delcourt N, Langrand J, Puskarczyk E, Nisse P, Sinno-Tellier S, de Haro L. Snake bites by European vipers in Mainland France in 2017-2018: comparison of two antivenoms Viperfav^® and Viperatab^®. Clin Toxicol (Phila). 2020 Nov;58(11):1050-1057. Epub 2020 Mar 5. PMID: 32134691. https://doi.org/10.1080/15563650.2020.1726377

Sweden

• Karlson-Stiber C, Salmonson H, Persson H. A nationwide study of Vipera berus bites during one year-epidemiology and morbidity of 231 cases. Clin Toxicol (Phila). 2006;44(1):25-30. PMID: 16496490. https://doi.org/10.1080/15563650500394597
• Persson H, Irestedt B. A study of 136 cases of adder bite treated in Swedish hospitals during one year. Acta Med Scand. 1981;210(6):433-9. doi: 10.1111/j.0954-6820.1981.tb09845.x. PMID: 7331888. https://doi.org/10.1111/j.0954-6820.1981.tb09845.x

Switzerland

• Fuchs J, Gessner T, Kupferschmidt H, Weiler S. Indigenous venomous snakebites in Switzerland: analysis of reports to the National Poisons Information Centre over 22 years. Swiss Med Wkly. 2021 Dec 16;151:w30085. PMID: 34964582. https://doi.org/10.4414/smw.2021.w30085
• Petite J. Viper bites: treat or ignore? Review of a series of 99 patients bitten by Vipera aspis in an alpine Swiss area. Swiss Med Wkly. 2005 Oct 15;135(41-42):618-25. PMID: 16380847. https://doi.org/10.4414/smw.2005.11198
• Stahel E, Wellauer R, Freyvogel TA.Vergiftungen durch einheimische Vipern (Vipera berus und Vipera aspis).Eine retrospektive Studie an 113 Patienten [Poisoning by domestic vipers (Vipera berus and Vipera aspis). A retrospective study of 113 patients]. Schweiz Med Wochenschr. 1985 Jun 29;115(26):890-6. German. PMID: 4023676.

United Kingdom

• Gerrard M, Pugh R. An adder bite with unusual consequences. Practitioner 1982;226:527-8
• Lamb T, Stewart D, Warrell DA, Lalloo DG, Jagpal P, Jones D, Thanacoody R, Gray LA, Eddleston M. Moderate-to-severe Vipera berus envenoming requiring ViperaTAb antivenom therapy in the UK. Clin Toxicol (Phila). 2021 Nov;59(11):992-1001. Epub 2021 Mar 15. PMID: 33720783. https://doi.org/10.1080/15563650.2021.1891245
• Reid HA. Adder bites in Britain. Br Med J. 1976 Jul 17;2(6028):153-6. PMID: 1276841; PMCID: PMC1687390. https://doi.org/10.1136/bmj.2.6028.153
• Warrell DA.Treatment of bites by adders and exotic venomous snakes. BMJ. 2005 Nov 26;331(7527):1244-7. Erratum in: BMJ. 2006 Jan 21;332(7534):151. PMID: 16308385; PMCID: PMC1289323. https://doi.org/10.1136/bmj.331.7527.1244