Journal of Toxicology

CLINICAL TOXICOLOGY

Vol 42 No 5 pp 635ndash641 2004

Rattlesnake Bites in EuropemdashExperiences from Southeastern France andNorthern Germany

Andreas Schaper1 Luc de Haro2 Herbert Desel1 Martin Ebbecke1

and Claus Langer3

1GIZ-Nord Poison Centre University of Gottingen Gottingen Germany2Centre Antipoison Marseille France

3Department of General Surgery University of Gottingen Gottingen Germany

ABSTRACT

Introduction Rattlesnakes are indigenous to the New World and hence their

envenomations are a significant percentage of all poisonings in North and South

America Some years ago rattlesnake bites were virtually unknown in Europe But the

biodiversity of European household fauna has changed cats and dogs are increasingly

replaced by stingrays tarantulas fire fish and rattlesnakes This phenomenon is the

background of a FrenchndashGerman cooperation to evaluate the relevance of rattlesnake

bites for European doctors Material and Methods In a retrospective study all

consultations of the GIZ-Nord poison centre in Gottingen and the Centre Antipoison

in Marseille concerning bites of poisonous snakes in a 20-yr time period were

analyzed Results Altogether 671 cases of poisonous snake bites were registered

Rattlesnake bites came up to 21 (31 of all consultations due to poisonous snake

bites) Over the years the number increased constantly All patients were adult men

with a mean age of 372 (20ndash64) years There were no females and no pediatric

patients involved According to the Poisoning Severity Score there were 8 minor

5 moderate and 8 severe envenomations no fatalities The leading clinical symptoms

consisted of rhabdomyolysis neurological and coagulational disorders In 5 cases

antivenom therapy was applied and in 4 patients surgical therapy was performed

Conclusion Rattlesnake bites are rare in Europe but the incidence is rising The

patientsrsquo profile is different from large American case series European doctors should

be aware of the increase in these infrequent envenomations

Key Words Rattlesnake bites Envenomations Poisoning Biodiversity

Correspondence Dr Andreas Schaper GIZ-Nord Poison Center II (Giftinformationszentrum-Nord der Lander Bremen Hamburg

Niedersachsen und Schleswig-Holstein) Zentrum Pharmakologie und Toxikologie Georg August Universitat Bereich Human-

medizin Robert-Koch-Str 40 D-37075 Gottingen Germany Fax +49-551-3831881 E-mail aschapergiz-nordde

635

DOI 101081CLT-200026962 0731-3810 (Print) 1097-9875 (Online)

Copyright D 2004 by Marcel Dekker Inc wwwdekkercom

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INTRODUCTION

Poisonous snake bites play an important role in

medical care all over the world The World Health

Organization estimates approximately 50000 deaths

each year caused by the bites of poisonous snakes

worldwide (1) Most of these fatalities take place in

rural areas of Asia South America and Africa Never-

theless the number of deaths following a poisonous

snake bite is approximately 10 in the United States

each year (1)

Until recently these incidents were virtually un-

known to physicians in France or Germany But the

biodiversity of pets in European households has

increased Cats and dogs have been replaced by snakes

tarantulas and venomous fish or stingrays Physicians

in Europe encounter an increasing number of exotic

animal bites

This study represents a FrenchndashGerman coopera-

tion concerning our experiences with this exposure

towards poisonous animals In a retrospective study we

analyzed our cases of poisonous snake bites in North-

ern Germany and Southeastern France A special focus

was placed on antivenom and surgical therapy in these

envenomations The study was designed to provide a

survey of our experiences with rattlesnake bites and to

summarize indications and criteria for antivenom and

surgical therapy

MATERIAL AND METHODS

In a retrospective study all consultations of the

GIZ-Nord poison center at Gottingen University and

the Centre Antipoison at Marseille concerning bites of

poisonous snakes in a 20-yr time period were analyzed

with a special focus on rattlesnakes In order to esti-

mate the relevance of poisonous snakes the figures

were put in relationship to all consultations concerning

poisonous animals

The poison center in Gottingen is responsible for the

northern part of Germany including the states of Bremen

Hamburg Schleswig-Holstein and Lower Saxonymdashthus

representing a population of about 12 million people

The catchment area of the Marseille poison center

consists of three French regions (Provence Languedoc

and Corsica) with approximately 7 million inhabitants

In most cases the taxonomy ie the exact

biological identification of the snake was determined

(usually by the patients who were the owners of the

rattlesnakes) Moreover all rattlesnake cases were

classified according to the Poisoning Severity Score

(2) Demographic data of all patients and their outcome

were investigated The modus of intoxication (acciden-

talmdashoccupationalat homemdashsuicidal) was classified and

the indications for antivenom and surgical therapy were

analyzed The numerical development over the years

was determined

RESULTS

From 1983ndash2002 the GIZ-Nord poison center and

the Centre Antipoison in Marseille were involved in

12400 cases of poisonous animals (Marseille 10624

cases and Gottingen 1776 cases) During this period

the two poison centers were consulted in 671 cases due

to poisonous snake bites (Marseille 367 cases and

Gottingen 304 cases) Thus the consultations due to

venomous snakes made up 54 of all exposures to

venomous animals

Altogether the number of rattlesnake bites

amounted to 21 (31 of all cases concerning poi-

sonous snake bites) There were 8 Marseille and 13

Gottingen patients

The numerical development is depicted in Fig 1

There was one case per year in 1983 1989 1996 and

1998 two cases in 1990 and 1997 three cases in 2001

and five rattlesnake bites in the years 2000 and 2002

Table 1 gives an overview of the cases and the

clinical symptoms All the patients were male and the

average age was 372 (20ndash64) years There were no

children among the patients All but one case (patient

2) were accidental In this only case of an inten-

tional intoxication a 32-yr-old man tried to commit

suicide by being bitten by his exotic pet a Sistrurus

miliarius or pigmy rattlesnake the result was only a

moderate intoxication

One accidental bite took place in an occupation-

al setting a 48-yr-old man was bitten at work (a

Figure 1 Numerical development of rattlesnake bites in

Northern Germany and Southeastern France n=21 1983ndash

2002

636 Schaper et al

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professional snake farm) when he was about to harvest

the venom of a Crotalus durissus terrificus (patient 4)

The patient developed a severe intoxication with res-

piratory insufficiency and had to be ventilated mechani-

cally for 10 days

According to the Poisoning Severity Score the

following classification was carried out there were

8 minor 5 moderate and 8 severe intoxications no

fatalities were registered 57 of the patients (12 of

21) developed clinical signs of systemic toxicity (see

Table 1) In two cases mechanical ventilation was

necessary Three patients developed rhabdomyolysis

one with a creatinine kinase activity of 34000 UL

[270 UL] Coagulational disorders were common they

developed in 33 of the patients (7 of 21) In one case

of a 32-yr-old man subcutaneous bleeding in the right

upper arm was detected

In 5 of the 21 cases an antivenom therapy was

performed (PSS 4 severe and 1 minor intoxication) In

Table 1 these are the patients 9 11 12 14 and 16

The indications consisted of symptoms such as

rhabdomyolysis coagulation disorders and neurologic

impairment including respiratory insufficiency caused

by toxic paralysis In 4 cases there was an indication

for surgical treatment (patients 1 6 12 and 15) such

as abscesses or compartment syndromes (Fig 2)

Table 1 Overview of 21 rattlesnake bites (Centre Antipoison Marseille and GIZ-Nord poison center Gottingen 1983ndash2002)

Age (years) Taxonomy PSS-level Systemic toxicity Antivenom Operation

1 30 Crotalus atrox Severe Hypotension

coagulation disorder

+

2 32 Sistrurus miliarius Moderate 3 35 Sistrurus miliarius Minor Paresthesia 4 48 Crotalus durissus

terrificus

Severe Intubation resp

insufficiency

5 50 Crotalus atrox Severe Coagulation disorder 6 20 Sistrurus miliarius Moderate +

7 53 Crotalus viridis Severe Hypotension coagulation

disorder

8 64 Crotalus durissus

terrificus

Moderate Rhabdomyolysis drowsiness

dyspnea

9 35 Crotalus sp Minor + 10 35 Agkistrodon

piscivorus

Minor

11 33 Crotalus

adamanteus

Severe Intubation coagulation

disorder

+

12 Adult Crotalus sp Severe Coagulation disorder + +

13 30 Sistrurus

miliarius

Moderate

14 Adult Crotalus

adamanteus

Severe Coagulation disorder +

15 35 Sistrurus miliarius Moderate Coagulation disorder

rhabdomyolysis

+

16 21 Crotalus sp Severe Rhabdomyolysis + 17 Adult Crotalus sp Minor 18 Adult Crotalus atrox Minor 19 37 Agkistrodon

contortrix

Minor Swelling of local

lymph nodes

20 Adult Agkistrodon

piscivorus

Minor

21 Adult Agkistrodon

contortrix

Minor

Summary Average

372

12 Crotalus sp 8 Severe 12 (21) 5 (21) 4 (21)

5 Agkistrodon sp 5 Moderate 57 24 19

4 Sistrurus mil 8 Minor

Rattlesnake Bites in Europe 637

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Due to a lack of documentation the exact time of

hospital stay cannot be reported In summary there

were no major complications and no long-term

sequelae were registered Concerning snake taxonomy

there were 12 cases of Crotalus (Fig 3) 5 of

Agkistrodon and 4 cases of Sistrurus or pigmy rattle

snake (Fig 4) The exact scientific names of the

rattlesnakes that had caused the injuries in the 21

reported cases are listed in Table 1

DISCUSSION

Rattlesnakes are indigenous to the New World (3)

Their length varies between 40 cm and 25 meters

Three genera belong to the family Crotalidae (pit

vipers) Agkistrodon Crotalus and Sistrurus Agkis-

trodon snakes include copperhead cottonmouth and

water moccasin snakes Crotalus are the rattlesnakes in

the strict sense whereas Sistrurus are Massasauga or

pigmy rattlesnakes They can be encountered in all

different habitats from deserts to humid jungles and in

mountain areas up to an altitude of approximately

4000 meters

The name lsquolsquopit viperrsquorsquo refers to a depression or

lsquolsquopitrsquorsquo located midway between the eye and the nostril

(arrow in Fig 4) This pit represents a heat-receptor

organ which senses the presence and location of warm-

blooded prey and predators (4) The characteristic

sound of the rattle is a warning signal for potential

enemies After every shedding an additional segment

lengthens and enlarges this organ which gave the

name to the whole family (circled in Fig 3)

The only native poisonous snakes that are

encountered in France and Germany are Vipera aspis

and Vipera berus Compared with snake bites in

America rattlesnake bites are infrequent in Germany

and France Considering the changing fauna in Europe-

an households these envenomations have become more

and more important to French and German doctors

Taking the development of rattlesnake bites in parts of

Europe (Fig 1) into account this problem becomes

increasingly important for European health care In

several publications this European trend to exotic pets

and the increasing number of injuries caused by poi-

sonous animals are described (5ndash7) The authors cannot

supply data about the numerical development of govern-

mental permits for venomous animalsFigure 3 Crotalus durissus terrificus circle around the

rattle

Figure 4 Sistrurus miliarius or pigmy arrow marks the pit

(hence pit vipers details in text)

Figure 2 Local effect of a rattlesnake bite in the right index

finger (patient 15)

638 Schaper et al

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Concerning demographic data there is an obvious

difference between the American publications (89) and

the European results (56) Whereas there were no

children among our patients (the youngest victim was

20 yrs old) this group of young patients especially

represents an important focus in the American litera-

ture The reason might be that in Europe there are

virtually no accidents with rattlesnakes outside the

housemdashthe snakes are exclusively held as pets in terraria

within the household

The venom of these poisonous snakes consists of

various toxic components including a mixture of

proteins with enzymatic activities Some heat-stable

hemorrhagic toxins (10) citrate (11) and Barbourin

were characterized The latter might have therapeutic

value as a platelet aggregation inhibitor (12) Referring

to toxicity in general Minton and Weinstein (1984)

published an LD 50 of the venom produced by

Crotalus tigris for rats this came up to 0056 mgkg

iv and 021 mgkg after subcutaneous injection (13)

The venom can cause both local and systemic

damage The toxic proteins can be grouped into

neurotoxins myotoxins and hemorrhagic components

Scientists of different provenance are interested in

these venoms Hence there does exist a broad variety

of publications concerning rattlesnakes Whereas med-

ical doctors surgeons or neurologists put their focus

on the clinical aspects (81415) on the other hand

biologists biochemists and chemists characterize the

venom (16ndash18) Molecular biologists compare differ-

ent genetic patterns to carry out gene mapping (1920)

Moreover pharmacological aspects should not be un-

derestimated several drugs are produced from snake

venoms The most important target is the coagulation

system Coagulation disorders seem to be the most

common and leading symptom (79) in rattlesnake

envenomations About a third of our patients developed

coagulation disorders Sometimes these symptoms are

clinically obvious but are rather difficult to demon-

strate in the laboratory results One of our patients for

example showed a subcutaneous bleeding in his right

upper armmdashhis coagulation tests were all normal

with the exception of a mild thrombocytopenia of

102000ml [150000ndash300000] which does not explain

the bleeding This phenomenon seems to be well

possible since not all components of the rattlesnake

venom have been characterized yet There does exist a

dose-dependency of the venom concerning its ability to

alter the coagulation system several publications

showed a hypercoagulability after application of low

doses and a hypocoagulability thus bleeding after

higher doses (2122) Twenty-five percent of our

patients showed neurological symptoms the most

severe being respiratory insufficiency Four patients

needed mechanical ventilation One example of a

neurotoxic serpentine venom is a-neurotoxin it is able

to block the nicotinic acetylcholine receptor being part

of a tubular transmembrane protein This receptor

consists of 5 subunits (2 a-areas one b- one g- and

one d-subunit) The toxin hinders acetylcholine from

binding at the a-area and thus leading to an inability to

open the channel This blocking of the a-subunit

means that potassium ions cannot be transported

through the membrane and neurotransmissional signals

are discontinued

Another group of toxins is represented by

myotoxins The myotoxin-alpha-like protein for exam-

ple can cause severe rhabdomyolysis with consecutive

renal insufficiency In our patients we detected

rhabdomyolysis in 15 of all cases One patient

developed a CK of some 34000 UL One toxicolog-

ical mechanismmdashdirect toxicity for the musclesmdashcould

be triggered by this myotoxin-alpha-like protein (16)

Whereas severe rhabdomyolysis is not uncommon in

Crotalus envenomations it is infrequent concerning

Sistrurus snake bites The first case of rhabdomyolysis

with consecutive renal failure after a pigmy rattlesnake

bite was published 1991 by Ahlstrom et al (1)

In summary the clinical effects of rattlesnake and

pigmy bites are caused by three groups of toxins

hemorrhagins are responsible for coagulation disorders

neurotoxins can lead to paralyses and rhabdomyolysis

develops due to myotoxins

Apart from symptomatic therapy of rattlesnake bites

two specific regimen exist On the one hand an

antivenom is available On the other hand surgical

treatment may be necessary A very comprehensive

review including all different aspects of snake anti-

venoms especially the risks and side effects of

antivenom treatment was published in Clinical Toxicol-

ogy only recently (23) In consent with these authors we

suggest the indication for the application of antivenom

to be very strict since there is a high probability of

developing hypersensivity reactions especially serum

sickness The figures of the development of serious

side effects of the antivenom vary between 10 and

more than 50 (923) In our opinion it should only be

applied in severe envenomation Antivenom therapy

should always be performed under intensive-care mon-

itoring The indications consist of increasing local ef-

fects like necrosis and a deterioration of the systemic

toxic effects such as the impairment of coagulational or

development of neurological symptoms Because of the

serious potential side effects a prophylactic application

Rattlesnake Bites in Europe 639

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should be omitted Concerning the availability of snake

antivenom the situation is very heterogenous in Europe

most poison centers do not store the antivenom Usually

the antivenom is available in university hospitals but

only in a small number of poison centers In our opinion

this heterogeneity can affect the treatment of the pa-

tients retrospectively some of the patients who did not

get the antivenom should have been treated on the

other hand at least one patient who was treated did not

need the antivenom

Concerning surgical treatment the indication

should be strict as well the development of abscesses

or a threatening compartment syndrome are reasons for

surgery Severe local effects even circumscribed

necrosis are not necessarily an indication for surgery

Taking the potential side effects into account these

local symptoms can be treated very effectively by

antivenom The excision of the fangmark is discussed

controversially in literature a probable foreign body in

the wound can be an indication for surgical treatment

The experience concerning these envenomations is

limited in Europe but several studies from the United

States draw similar conclusions (8914)

In conclusion the indication for both antivenom

therapy and for surgical treatment following rattlesnake

bites should be very strict Increasing systemic effects

of the toxins are indications for antivenom therapy

Surgical treatment is necessary in cases of abscess or

compartment syndrome

REFERENCES

1 Ahlstrom NG Luginbuhl W Tisher CC Acute

anuric renal failure after pigmy rattlesnake bite

South Med J Jun 1991 84(6)783ndash785

2 Persson HE Sjoberg GK Haines JA Pronczuk de

Garbino J Poisoning severity score Grading of

acute poisoning J Toxicol Clin Toxicol 199836(3)205ndash213

3 Tu AT Preface Rattlesnake Venoms 1st ed New

York Marcel Dekker Inc 1982 V

4 Kass L Loop MS Hartline PH Anatomical and

physiological localization of visual and infrared

cell layers in tectum of pit vipers J Comp Neurol

Dec 15 1978 182(4 Pt 2)811ndash820

5 de Haro L Hayek-Lanthois M Jouglard J-P David

J-M Jouglard J Envenimations par serpents

exotiques bilan du centre anti-poison de Marseille

Bull Soc Herp Fr 1995 75ndash7651ndash566 de Haro L Pommier P Envenomation a real risk

of keeping exotic house pets Vet Hum Toxicol

August 2003 45(4)214ndash216

7 Bismuth C Chouvalidze N Baud F Soria C

Drouet L Tobelem G Defibrination Pure Apres

Morsure de Crotale Horridus La Presse Medicale

1983 291 15 janvier 12 N8 Shaw BA Hosalkar HS Rattlesnake bites in

children antivenin treatment and surgical indica-

tions J Bone Jt Surg Am Sep 2002 84-

A(9)1624ndash1629

9 White RR IV Weber RA Poisonous snakebite in

central Texas Possible indicators for antivenin

treatment Ann Surg May 1991 213(5)466ndash471

discussion 471ndash472

10 Ownby CL Colberg TR Li Q Presence of heat-

stable hemorrhagic toxins in snake venoms

Toxicon Aug 1994 32(8)945ndash954

11 Freitas MA Geno PW Sumner LW Cooke ME

Hudiburg SA Ownby CL Kaiser II Odell Citrate

is a major component of snake venoms Toxicon

Apr 1992 30(4)461ndash464

12 Scarborough RM Rose JW Hsu MA Phillips DR

Fried VA Campbell AM Nannizzi L Charo IF

Barbourin A GPIIb-IIIa-specific integrin an-

tagonist from the venom of Sistrurus m barbouri

J Biol Chem May 25 1991 266(15)9359ndash

9362

13 Minton SA Weinstein SA Protease activity and

lethal toxicity of venoms from some little known

rattlesnakes Toxicon 1984 22(5)828ndash830

14 Weber RA White RR IV Crotalidae envenoma-

tion in children Ann Plast Surg Aug 199331(2)141ndash145

15 de Haro L Envenimations Rev Prat Feb 15 200050(4)401ndash406

16 Bober MA Glenn JL Straight RC Ownby CL

Detection of myotoxin alpha-like proteins in

various snake venoms Toxicon 1988 26(7)

665ndash673

17 Foote R MacMahon JA Electrophoretic studies of

rattlesnake (Crotalus and Sistrurus) venom taxo-

nomic implications Comp Biochem Physiol B

1977 57(3)23

18 Mebs D Pohlmann S Von Tenspolde W Snake

venom hemorrhagins neutralization by com-

mercial antivenoms Toxicon 1988 26(5)453ndash

458

19 Gibbs HL Prior KA Weatherhead PJ Johnson

G Genetic structure of populations of the

threatened eastern massasauga rattlesnake Sis-

trurus c catenatus evidence from microsatellite

DNA markers Mol Ecol Dec 1997 6(12)1123ndash

1132

20 Lougheed SC Gibbs HL Prior KA Weatherhead

PJ A comparison of RAPD versus microsatellite

640 Schaper et al

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DNA markers in population studies of the massa-

sauga rattlesnake J Heredity NovndashDec 200091(6)458ndash463

21 Assi AA Nasser H An in vitro and in vivo study

of some biological and biochemical effects of

Sistrurus Malarius Barbouri venom Toxicology

Sep 20 1999 137(2)81ndash94

22 Tan NH Ponnudurai G A comparative study of

the biological activities of rattlesnake (genera

Crotalus and Sistrurus) venoms Comp Biochem

Physiol C 1991 98(2ndash3)455ndash461

23 Lalloo DG Theakston RD Snake antivenoms J

Toxicol Clin Toxicol 2003 41(3) pp 277ndash290

317ndash327

Submitted January 14 2004

Accepted May 18 2004

Rattlesnake Bites in Europe 641

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professional snake farm) when he was about to harvest

the venom of a Crotalus durissus terrificus (patient 4)

The patient developed a severe intoxication with res-

piratory insufficiency and had to be ventilated mechani-

cally for 10 days

According to the Poisoning Severity Score the

following classification was carried out there were

8 minor 5 moderate and 8 severe intoxications no

fatalities were registered 57 of the patients (12 of

21) developed clinical signs of systemic toxicity (see

Table 1) In two cases mechanical ventilation was

necessary Three patients developed rhabdomyolysis

one with a creatinine kinase activity of 34000 UL

[270 UL] Coagulational disorders were common they

developed in 33 of the patients (7 of 21) In one case

of a 32-yr-old man subcutaneous bleeding in the right

upper arm was detected

In 5 of the 21 cases an antivenom therapy was

performed (PSS 4 severe and 1 minor intoxication) In

Table 1 these are the patients 9 11 12 14 and 16

The indications consisted of symptoms such as

rhabdomyolysis coagulation disorders and neurologic

impairment including respiratory insufficiency caused

by toxic paralysis In 4 cases there was an indication

for surgical treatment (patients 1 6 12 and 15) such

as abscesses or compartment syndromes (Fig 2)

Table 1 Overview of 21 rattlesnake bites (Centre Antipoison Marseille and GIZ-Nord poison center Gottingen 1983ndash2002)

Age (years) Taxonomy PSS-level Systemic toxicity Antivenom Operation

1 30 Crotalus atrox Severe Hypotension

coagulation disorder

+

2 32 Sistrurus miliarius Moderate 3 35 Sistrurus miliarius Minor Paresthesia 4 48 Crotalus durissus

terrificus

Severe Intubation resp

insufficiency

5 50 Crotalus atrox Severe Coagulation disorder 6 20 Sistrurus miliarius Moderate +

7 53 Crotalus viridis Severe Hypotension coagulation

disorder

8 64 Crotalus durissus

terrificus

Moderate Rhabdomyolysis drowsiness

dyspnea

9 35 Crotalus sp Minor + 10 35 Agkistrodon

piscivorus

Minor

11 33 Crotalus

adamanteus

Severe Intubation coagulation

disorder

+

12 Adult Crotalus sp Severe Coagulation disorder + +

13 30 Sistrurus

miliarius

Moderate

14 Adult Crotalus

adamanteus

Severe Coagulation disorder +

15 35 Sistrurus miliarius Moderate Coagulation disorder

rhabdomyolysis

+

16 21 Crotalus sp Severe Rhabdomyolysis + 17 Adult Crotalus sp Minor 18 Adult Crotalus atrox Minor 19 37 Agkistrodon

contortrix

Minor Swelling of local

lymph nodes

20 Adult Agkistrodon

piscivorus

Minor

21 Adult Agkistrodon

contortrix

Minor

Summary Average

372

12 Crotalus sp 8 Severe 12 (21) 5 (21) 4 (21)

5 Agkistrodon sp 5 Moderate 57 24 19

4 Sistrurus mil 8 Minor

Rattlesnake Bites in Europe 637

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Due to a lack of documentation the exact time of

hospital stay cannot be reported In summary there

were no major complications and no long-term

sequelae were registered Concerning snake taxonomy

there were 12 cases of Crotalus (Fig 3) 5 of

Agkistrodon and 4 cases of Sistrurus or pigmy rattle

snake (Fig 4) The exact scientific names of the

rattlesnakes that had caused the injuries in the 21

reported cases are listed in Table 1

DISCUSSION

Rattlesnakes are indigenous to the New World (3)

Their length varies between 40 cm and 25 meters

Three genera belong to the family Crotalidae (pit

vipers) Agkistrodon Crotalus and Sistrurus Agkis-

trodon snakes include copperhead cottonmouth and

water moccasin snakes Crotalus are the rattlesnakes in

the strict sense whereas Sistrurus are Massasauga or

pigmy rattlesnakes They can be encountered in all

different habitats from deserts to humid jungles and in

mountain areas up to an altitude of approximately

4000 meters

The name lsquolsquopit viperrsquorsquo refers to a depression or

lsquolsquopitrsquorsquo located midway between the eye and the nostril

(arrow in Fig 4) This pit represents a heat-receptor

organ which senses the presence and location of warm-

blooded prey and predators (4) The characteristic

sound of the rattle is a warning signal for potential

enemies After every shedding an additional segment

lengthens and enlarges this organ which gave the

name to the whole family (circled in Fig 3)

The only native poisonous snakes that are

encountered in France and Germany are Vipera aspis

and Vipera berus Compared with snake bites in

America rattlesnake bites are infrequent in Germany

and France Considering the changing fauna in Europe-

an households these envenomations have become more

and more important to French and German doctors

Taking the development of rattlesnake bites in parts of

Europe (Fig 1) into account this problem becomes

increasingly important for European health care In

several publications this European trend to exotic pets

and the increasing number of injuries caused by poi-

sonous animals are described (5ndash7) The authors cannot

supply data about the numerical development of govern-

mental permits for venomous animalsFigure 3 Crotalus durissus terrificus circle around the

rattle

Figure 4 Sistrurus miliarius or pigmy arrow marks the pit

(hence pit vipers details in text)

Figure 2 Local effect of a rattlesnake bite in the right index

finger (patient 15)

638 Schaper et al

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

Concerning demographic data there is an obvious

difference between the American publications (89) and

the European results (56) Whereas there were no

children among our patients (the youngest victim was

20 yrs old) this group of young patients especially

represents an important focus in the American litera-

ture The reason might be that in Europe there are

virtually no accidents with rattlesnakes outside the

housemdashthe snakes are exclusively held as pets in terraria

within the household

The venom of these poisonous snakes consists of

various toxic components including a mixture of

proteins with enzymatic activities Some heat-stable

hemorrhagic toxins (10) citrate (11) and Barbourin

were characterized The latter might have therapeutic

value as a platelet aggregation inhibitor (12) Referring

to toxicity in general Minton and Weinstein (1984)

published an LD 50 of the venom produced by

Crotalus tigris for rats this came up to 0056 mgkg

iv and 021 mgkg after subcutaneous injection (13)

The venom can cause both local and systemic

damage The toxic proteins can be grouped into

neurotoxins myotoxins and hemorrhagic components

Scientists of different provenance are interested in

these venoms Hence there does exist a broad variety

of publications concerning rattlesnakes Whereas med-

ical doctors surgeons or neurologists put their focus

on the clinical aspects (81415) on the other hand

biologists biochemists and chemists characterize the

venom (16ndash18) Molecular biologists compare differ-

ent genetic patterns to carry out gene mapping (1920)

Moreover pharmacological aspects should not be un-

derestimated several drugs are produced from snake

venoms The most important target is the coagulation

system Coagulation disorders seem to be the most

common and leading symptom (79) in rattlesnake

envenomations About a third of our patients developed

coagulation disorders Sometimes these symptoms are

clinically obvious but are rather difficult to demon-

strate in the laboratory results One of our patients for

example showed a subcutaneous bleeding in his right

upper armmdashhis coagulation tests were all normal

with the exception of a mild thrombocytopenia of

102000ml [150000ndash300000] which does not explain

the bleeding This phenomenon seems to be well

possible since not all components of the rattlesnake

venom have been characterized yet There does exist a

dose-dependency of the venom concerning its ability to

alter the coagulation system several publications

showed a hypercoagulability after application of low

doses and a hypocoagulability thus bleeding after

higher doses (2122) Twenty-five percent of our

patients showed neurological symptoms the most

severe being respiratory insufficiency Four patients

needed mechanical ventilation One example of a

neurotoxic serpentine venom is a-neurotoxin it is able

to block the nicotinic acetylcholine receptor being part

of a tubular transmembrane protein This receptor

consists of 5 subunits (2 a-areas one b- one g- and

one d-subunit) The toxin hinders acetylcholine from

binding at the a-area and thus leading to an inability to

open the channel This blocking of the a-subunit

means that potassium ions cannot be transported

through the membrane and neurotransmissional signals

are discontinued

Another group of toxins is represented by

myotoxins The myotoxin-alpha-like protein for exam-

ple can cause severe rhabdomyolysis with consecutive

renal insufficiency In our patients we detected

rhabdomyolysis in 15 of all cases One patient

developed a CK of some 34000 UL One toxicolog-

ical mechanismmdashdirect toxicity for the musclesmdashcould

be triggered by this myotoxin-alpha-like protein (16)

Whereas severe rhabdomyolysis is not uncommon in

Crotalus envenomations it is infrequent concerning

Sistrurus snake bites The first case of rhabdomyolysis

with consecutive renal failure after a pigmy rattlesnake

bite was published 1991 by Ahlstrom et al (1)

In summary the clinical effects of rattlesnake and

pigmy bites are caused by three groups of toxins

hemorrhagins are responsible for coagulation disorders

neurotoxins can lead to paralyses and rhabdomyolysis

develops due to myotoxins

Apart from symptomatic therapy of rattlesnake bites

two specific regimen exist On the one hand an

antivenom is available On the other hand surgical

treatment may be necessary A very comprehensive

review including all different aspects of snake anti-

venoms especially the risks and side effects of

antivenom treatment was published in Clinical Toxicol-

ogy only recently (23) In consent with these authors we

suggest the indication for the application of antivenom

to be very strict since there is a high probability of

developing hypersensivity reactions especially serum

sickness The figures of the development of serious

side effects of the antivenom vary between 10 and

more than 50 (923) In our opinion it should only be

applied in severe envenomation Antivenom therapy

should always be performed under intensive-care mon-

itoring The indications consist of increasing local ef-

fects like necrosis and a deterioration of the systemic

toxic effects such as the impairment of coagulational or

development of neurological symptoms Because of the

serious potential side effects a prophylactic application

Rattlesnake Bites in Europe 639

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

should be omitted Concerning the availability of snake

antivenom the situation is very heterogenous in Europe

most poison centers do not store the antivenom Usually

the antivenom is available in university hospitals but

only in a small number of poison centers In our opinion

this heterogeneity can affect the treatment of the pa-

tients retrospectively some of the patients who did not

get the antivenom should have been treated on the

other hand at least one patient who was treated did not

need the antivenom

Concerning surgical treatment the indication

should be strict as well the development of abscesses

or a threatening compartment syndrome are reasons for

surgery Severe local effects even circumscribed

necrosis are not necessarily an indication for surgery

Taking the potential side effects into account these

local symptoms can be treated very effectively by

antivenom The excision of the fangmark is discussed

controversially in literature a probable foreign body in

the wound can be an indication for surgical treatment

The experience concerning these envenomations is

limited in Europe but several studies from the United

States draw similar conclusions (8914)

In conclusion the indication for both antivenom

therapy and for surgical treatment following rattlesnake

bites should be very strict Increasing systemic effects

of the toxins are indications for antivenom therapy

Surgical treatment is necessary in cases of abscess or

compartment syndrome

REFERENCES

1 Ahlstrom NG Luginbuhl W Tisher CC Acute

anuric renal failure after pigmy rattlesnake bite

South Med J Jun 1991 84(6)783ndash785

2 Persson HE Sjoberg GK Haines JA Pronczuk de

Garbino J Poisoning severity score Grading of

acute poisoning J Toxicol Clin Toxicol 199836(3)205ndash213

3 Tu AT Preface Rattlesnake Venoms 1st ed New

York Marcel Dekker Inc 1982 V

4 Kass L Loop MS Hartline PH Anatomical and

physiological localization of visual and infrared

cell layers in tectum of pit vipers J Comp Neurol

Dec 15 1978 182(4 Pt 2)811ndash820

5 de Haro L Hayek-Lanthois M Jouglard J-P David

J-M Jouglard J Envenimations par serpents

exotiques bilan du centre anti-poison de Marseille

Bull Soc Herp Fr 1995 75ndash7651ndash566 de Haro L Pommier P Envenomation a real risk

of keeping exotic house pets Vet Hum Toxicol

August 2003 45(4)214ndash216

7 Bismuth C Chouvalidze N Baud F Soria C

Drouet L Tobelem G Defibrination Pure Apres

Morsure de Crotale Horridus La Presse Medicale

1983 291 15 janvier 12 N8 Shaw BA Hosalkar HS Rattlesnake bites in

children antivenin treatment and surgical indica-

tions J Bone Jt Surg Am Sep 2002 84-

A(9)1624ndash1629

9 White RR IV Weber RA Poisonous snakebite in

central Texas Possible indicators for antivenin

treatment Ann Surg May 1991 213(5)466ndash471

discussion 471ndash472

10 Ownby CL Colberg TR Li Q Presence of heat-

stable hemorrhagic toxins in snake venoms

Toxicon Aug 1994 32(8)945ndash954

11 Freitas MA Geno PW Sumner LW Cooke ME

Hudiburg SA Ownby CL Kaiser II Odell Citrate

is a major component of snake venoms Toxicon

Apr 1992 30(4)461ndash464

12 Scarborough RM Rose JW Hsu MA Phillips DR

Fried VA Campbell AM Nannizzi L Charo IF

Barbourin A GPIIb-IIIa-specific integrin an-

tagonist from the venom of Sistrurus m barbouri

J Biol Chem May 25 1991 266(15)9359ndash

9362

13 Minton SA Weinstein SA Protease activity and

lethal toxicity of venoms from some little known

rattlesnakes Toxicon 1984 22(5)828ndash830

14 Weber RA White RR IV Crotalidae envenoma-

tion in children Ann Plast Surg Aug 199331(2)141ndash145

15 de Haro L Envenimations Rev Prat Feb 15 200050(4)401ndash406

16 Bober MA Glenn JL Straight RC Ownby CL

Detection of myotoxin alpha-like proteins in

various snake venoms Toxicon 1988 26(7)

665ndash673

17 Foote R MacMahon JA Electrophoretic studies of

rattlesnake (Crotalus and Sistrurus) venom taxo-

nomic implications Comp Biochem Physiol B

1977 57(3)23

18 Mebs D Pohlmann S Von Tenspolde W Snake

venom hemorrhagins neutralization by com-

mercial antivenoms Toxicon 1988 26(5)453ndash

458

19 Gibbs HL Prior KA Weatherhead PJ Johnson

G Genetic structure of populations of the

threatened eastern massasauga rattlesnake Sis-

trurus c catenatus evidence from microsatellite

DNA markers Mol Ecol Dec 1997 6(12)1123ndash

1132

20 Lougheed SC Gibbs HL Prior KA Weatherhead

PJ A comparison of RAPD versus microsatellite

640 Schaper et al

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

DNA markers in population studies of the massa-

sauga rattlesnake J Heredity NovndashDec 200091(6)458ndash463

21 Assi AA Nasser H An in vitro and in vivo study

of some biological and biochemical effects of

Sistrurus Malarius Barbouri venom Toxicology

Sep 20 1999 137(2)81ndash94

22 Tan NH Ponnudurai G A comparative study of

the biological activities of rattlesnake (genera

Crotalus and Sistrurus) venoms Comp Biochem

Physiol C 1991 98(2ndash3)455ndash461

23 Lalloo DG Theakston RD Snake antivenoms J

Toxicol Clin Toxicol 2003 41(3) pp 277ndash290

317ndash327

Submitted January 14 2004

Accepted May 18 2004

Rattlesnake Bites in Europe 641

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

Due to a lack of documentation the exact time of

hospital stay cannot be reported In summary there

were no major complications and no long-term

sequelae were registered Concerning snake taxonomy

there were 12 cases of Crotalus (Fig 3) 5 of

Agkistrodon and 4 cases of Sistrurus or pigmy rattle

snake (Fig 4) The exact scientific names of the

rattlesnakes that had caused the injuries in the 21

reported cases are listed in Table 1

DISCUSSION

Rattlesnakes are indigenous to the New World (3)

Their length varies between 40 cm and 25 meters

Three genera belong to the family Crotalidae (pit

vipers) Agkistrodon Crotalus and Sistrurus Agkis-

trodon snakes include copperhead cottonmouth and

water moccasin snakes Crotalus are the rattlesnakes in

the strict sense whereas Sistrurus are Massasauga or

pigmy rattlesnakes They can be encountered in all

different habitats from deserts to humid jungles and in

mountain areas up to an altitude of approximately

4000 meters

The name lsquolsquopit viperrsquorsquo refers to a depression or

lsquolsquopitrsquorsquo located midway between the eye and the nostril

(arrow in Fig 4) This pit represents a heat-receptor

organ which senses the presence and location of warm-

blooded prey and predators (4) The characteristic

sound of the rattle is a warning signal for potential

enemies After every shedding an additional segment

lengthens and enlarges this organ which gave the

name to the whole family (circled in Fig 3)

The only native poisonous snakes that are

encountered in France and Germany are Vipera aspis

and Vipera berus Compared with snake bites in

America rattlesnake bites are infrequent in Germany

and France Considering the changing fauna in Europe-

an households these envenomations have become more

and more important to French and German doctors

Taking the development of rattlesnake bites in parts of

Europe (Fig 1) into account this problem becomes

increasingly important for European health care In

several publications this European trend to exotic pets

and the increasing number of injuries caused by poi-

sonous animals are described (5ndash7) The authors cannot

supply data about the numerical development of govern-

mental permits for venomous animalsFigure 3 Crotalus durissus terrificus circle around the

rattle

Figure 4 Sistrurus miliarius or pigmy arrow marks the pit

(hence pit vipers details in text)

Figure 2 Local effect of a rattlesnake bite in the right index

finger (patient 15)

638 Schaper et al

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

Concerning demographic data there is an obvious

difference between the American publications (89) and

the European results (56) Whereas there were no

children among our patients (the youngest victim was

20 yrs old) this group of young patients especially

represents an important focus in the American litera-

ture The reason might be that in Europe there are

virtually no accidents with rattlesnakes outside the

housemdashthe snakes are exclusively held as pets in terraria

within the household

The venom of these poisonous snakes consists of

various toxic components including a mixture of

proteins with enzymatic activities Some heat-stable

hemorrhagic toxins (10) citrate (11) and Barbourin

were characterized The latter might have therapeutic

value as a platelet aggregation inhibitor (12) Referring

to toxicity in general Minton and Weinstein (1984)

published an LD 50 of the venom produced by

Crotalus tigris for rats this came up to 0056 mgkg

iv and 021 mgkg after subcutaneous injection (13)

The venom can cause both local and systemic

damage The toxic proteins can be grouped into

neurotoxins myotoxins and hemorrhagic components

Scientists of different provenance are interested in

these venoms Hence there does exist a broad variety

of publications concerning rattlesnakes Whereas med-

ical doctors surgeons or neurologists put their focus

on the clinical aspects (81415) on the other hand

biologists biochemists and chemists characterize the

venom (16ndash18) Molecular biologists compare differ-

ent genetic patterns to carry out gene mapping (1920)

Moreover pharmacological aspects should not be un-

derestimated several drugs are produced from snake

venoms The most important target is the coagulation

system Coagulation disorders seem to be the most

common and leading symptom (79) in rattlesnake

envenomations About a third of our patients developed

coagulation disorders Sometimes these symptoms are

clinically obvious but are rather difficult to demon-

strate in the laboratory results One of our patients for

example showed a subcutaneous bleeding in his right

upper armmdashhis coagulation tests were all normal

with the exception of a mild thrombocytopenia of

102000ml [150000ndash300000] which does not explain

the bleeding This phenomenon seems to be well

possible since not all components of the rattlesnake

venom have been characterized yet There does exist a

dose-dependency of the venom concerning its ability to

alter the coagulation system several publications

showed a hypercoagulability after application of low

doses and a hypocoagulability thus bleeding after

higher doses (2122) Twenty-five percent of our

patients showed neurological symptoms the most

severe being respiratory insufficiency Four patients

needed mechanical ventilation One example of a

neurotoxic serpentine venom is a-neurotoxin it is able

to block the nicotinic acetylcholine receptor being part

of a tubular transmembrane protein This receptor

consists of 5 subunits (2 a-areas one b- one g- and

one d-subunit) The toxin hinders acetylcholine from

binding at the a-area and thus leading to an inability to

open the channel This blocking of the a-subunit

means that potassium ions cannot be transported

through the membrane and neurotransmissional signals

are discontinued

Another group of toxins is represented by

myotoxins The myotoxin-alpha-like protein for exam-

ple can cause severe rhabdomyolysis with consecutive

renal insufficiency In our patients we detected

rhabdomyolysis in 15 of all cases One patient

developed a CK of some 34000 UL One toxicolog-

ical mechanismmdashdirect toxicity for the musclesmdashcould

be triggered by this myotoxin-alpha-like protein (16)

Whereas severe rhabdomyolysis is not uncommon in

Crotalus envenomations it is infrequent concerning

Sistrurus snake bites The first case of rhabdomyolysis

with consecutive renal failure after a pigmy rattlesnake

bite was published 1991 by Ahlstrom et al (1)

In summary the clinical effects of rattlesnake and

pigmy bites are caused by three groups of toxins

hemorrhagins are responsible for coagulation disorders

neurotoxins can lead to paralyses and rhabdomyolysis

develops due to myotoxins

Apart from symptomatic therapy of rattlesnake bites

two specific regimen exist On the one hand an

antivenom is available On the other hand surgical

treatment may be necessary A very comprehensive

review including all different aspects of snake anti-

venoms especially the risks and side effects of

antivenom treatment was published in Clinical Toxicol-

ogy only recently (23) In consent with these authors we

suggest the indication for the application of antivenom

to be very strict since there is a high probability of

developing hypersensivity reactions especially serum

sickness The figures of the development of serious

side effects of the antivenom vary between 10 and

more than 50 (923) In our opinion it should only be

applied in severe envenomation Antivenom therapy

should always be performed under intensive-care mon-

itoring The indications consist of increasing local ef-

fects like necrosis and a deterioration of the systemic

toxic effects such as the impairment of coagulational or

development of neurological symptoms Because of the

serious potential side effects a prophylactic application

Rattlesnake Bites in Europe 639

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

should be omitted Concerning the availability of snake

antivenom the situation is very heterogenous in Europe

most poison centers do not store the antivenom Usually

the antivenom is available in university hospitals but

only in a small number of poison centers In our opinion

this heterogeneity can affect the treatment of the pa-

tients retrospectively some of the patients who did not

get the antivenom should have been treated on the

other hand at least one patient who was treated did not

need the antivenom

Concerning surgical treatment the indication

should be strict as well the development of abscesses

or a threatening compartment syndrome are reasons for

surgery Severe local effects even circumscribed

necrosis are not necessarily an indication for surgery

Taking the potential side effects into account these

local symptoms can be treated very effectively by

antivenom The excision of the fangmark is discussed

controversially in literature a probable foreign body in

the wound can be an indication for surgical treatment

The experience concerning these envenomations is

limited in Europe but several studies from the United

States draw similar conclusions (8914)

In conclusion the indication for both antivenom

therapy and for surgical treatment following rattlesnake

bites should be very strict Increasing systemic effects

of the toxins are indications for antivenom therapy

Surgical treatment is necessary in cases of abscess or

compartment syndrome

REFERENCES

1 Ahlstrom NG Luginbuhl W Tisher CC Acute

anuric renal failure after pigmy rattlesnake bite

South Med J Jun 1991 84(6)783ndash785

2 Persson HE Sjoberg GK Haines JA Pronczuk de

Garbino J Poisoning severity score Grading of

acute poisoning J Toxicol Clin Toxicol 199836(3)205ndash213

3 Tu AT Preface Rattlesnake Venoms 1st ed New

York Marcel Dekker Inc 1982 V

4 Kass L Loop MS Hartline PH Anatomical and

physiological localization of visual and infrared

cell layers in tectum of pit vipers J Comp Neurol

Dec 15 1978 182(4 Pt 2)811ndash820

5 de Haro L Hayek-Lanthois M Jouglard J-P David

J-M Jouglard J Envenimations par serpents

exotiques bilan du centre anti-poison de Marseille

Bull Soc Herp Fr 1995 75ndash7651ndash566 de Haro L Pommier P Envenomation a real risk

of keeping exotic house pets Vet Hum Toxicol

August 2003 45(4)214ndash216

7 Bismuth C Chouvalidze N Baud F Soria C

Drouet L Tobelem G Defibrination Pure Apres

Morsure de Crotale Horridus La Presse Medicale

1983 291 15 janvier 12 N8 Shaw BA Hosalkar HS Rattlesnake bites in

children antivenin treatment and surgical indica-

tions J Bone Jt Surg Am Sep 2002 84-

A(9)1624ndash1629

9 White RR IV Weber RA Poisonous snakebite in

central Texas Possible indicators for antivenin

treatment Ann Surg May 1991 213(5)466ndash471

discussion 471ndash472

10 Ownby CL Colberg TR Li Q Presence of heat-

stable hemorrhagic toxins in snake venoms

Toxicon Aug 1994 32(8)945ndash954

11 Freitas MA Geno PW Sumner LW Cooke ME

Hudiburg SA Ownby CL Kaiser II Odell Citrate

is a major component of snake venoms Toxicon

Apr 1992 30(4)461ndash464

12 Scarborough RM Rose JW Hsu MA Phillips DR

Fried VA Campbell AM Nannizzi L Charo IF

Barbourin A GPIIb-IIIa-specific integrin an-

tagonist from the venom of Sistrurus m barbouri

J Biol Chem May 25 1991 266(15)9359ndash

9362

13 Minton SA Weinstein SA Protease activity and

lethal toxicity of venoms from some little known

rattlesnakes Toxicon 1984 22(5)828ndash830

14 Weber RA White RR IV Crotalidae envenoma-

tion in children Ann Plast Surg Aug 199331(2)141ndash145

15 de Haro L Envenimations Rev Prat Feb 15 200050(4)401ndash406

16 Bober MA Glenn JL Straight RC Ownby CL

Detection of myotoxin alpha-like proteins in

various snake venoms Toxicon 1988 26(7)

665ndash673

17 Foote R MacMahon JA Electrophoretic studies of

rattlesnake (Crotalus and Sistrurus) venom taxo-

nomic implications Comp Biochem Physiol B

1977 57(3)23

18 Mebs D Pohlmann S Von Tenspolde W Snake

venom hemorrhagins neutralization by com-

mercial antivenoms Toxicon 1988 26(5)453ndash

458

19 Gibbs HL Prior KA Weatherhead PJ Johnson

G Genetic structure of populations of the

threatened eastern massasauga rattlesnake Sis-

trurus c catenatus evidence from microsatellite

DNA markers Mol Ecol Dec 1997 6(12)1123ndash

1132

20 Lougheed SC Gibbs HL Prior KA Weatherhead

PJ A comparison of RAPD versus microsatellite

640 Schaper et al

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

DNA markers in population studies of the massa-

sauga rattlesnake J Heredity NovndashDec 200091(6)458ndash463

21 Assi AA Nasser H An in vitro and in vivo study

of some biological and biochemical effects of

Sistrurus Malarius Barbouri venom Toxicology

Sep 20 1999 137(2)81ndash94

22 Tan NH Ponnudurai G A comparative study of

the biological activities of rattlesnake (genera

Crotalus and Sistrurus) venoms Comp Biochem

Physiol C 1991 98(2ndash3)455ndash461

23 Lalloo DG Theakston RD Snake antivenoms J

Toxicol Clin Toxicol 2003 41(3) pp 277ndash290

317ndash327

Submitted January 14 2004

Accepted May 18 2004

Rattlesnake Bites in Europe 641

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

Concerning demographic data there is an obvious

difference between the American publications (89) and

the European results (56) Whereas there were no

children among our patients (the youngest victim was

20 yrs old) this group of young patients especially

represents an important focus in the American litera-

ture The reason might be that in Europe there are

virtually no accidents with rattlesnakes outside the

housemdashthe snakes are exclusively held as pets in terraria

within the household

The venom of these poisonous snakes consists of

various toxic components including a mixture of

proteins with enzymatic activities Some heat-stable

hemorrhagic toxins (10) citrate (11) and Barbourin

were characterized The latter might have therapeutic

value as a platelet aggregation inhibitor (12) Referring

to toxicity in general Minton and Weinstein (1984)

published an LD 50 of the venom produced by

Crotalus tigris for rats this came up to 0056 mgkg

iv and 021 mgkg after subcutaneous injection (13)

The venom can cause both local and systemic

damage The toxic proteins can be grouped into

neurotoxins myotoxins and hemorrhagic components

Scientists of different provenance are interested in

these venoms Hence there does exist a broad variety

of publications concerning rattlesnakes Whereas med-

ical doctors surgeons or neurologists put their focus

on the clinical aspects (81415) on the other hand

biologists biochemists and chemists characterize the

venom (16ndash18) Molecular biologists compare differ-

ent genetic patterns to carry out gene mapping (1920)

Moreover pharmacological aspects should not be un-

derestimated several drugs are produced from snake

venoms The most important target is the coagulation

system Coagulation disorders seem to be the most

common and leading symptom (79) in rattlesnake

envenomations About a third of our patients developed

coagulation disorders Sometimes these symptoms are

clinically obvious but are rather difficult to demon-

strate in the laboratory results One of our patients for

example showed a subcutaneous bleeding in his right

upper armmdashhis coagulation tests were all normal

with the exception of a mild thrombocytopenia of

102000ml [150000ndash300000] which does not explain

the bleeding This phenomenon seems to be well

possible since not all components of the rattlesnake

venom have been characterized yet There does exist a

dose-dependency of the venom concerning its ability to

alter the coagulation system several publications

showed a hypercoagulability after application of low

doses and a hypocoagulability thus bleeding after

higher doses (2122) Twenty-five percent of our

patients showed neurological symptoms the most

severe being respiratory insufficiency Four patients

needed mechanical ventilation One example of a

neurotoxic serpentine venom is a-neurotoxin it is able

to block the nicotinic acetylcholine receptor being part

of a tubular transmembrane protein This receptor

consists of 5 subunits (2 a-areas one b- one g- and

one d-subunit) The toxin hinders acetylcholine from

binding at the a-area and thus leading to an inability to

open the channel This blocking of the a-subunit

means that potassium ions cannot be transported

through the membrane and neurotransmissional signals

are discontinued

Another group of toxins is represented by

myotoxins The myotoxin-alpha-like protein for exam-

ple can cause severe rhabdomyolysis with consecutive

renal insufficiency In our patients we detected

rhabdomyolysis in 15 of all cases One patient

developed a CK of some 34000 UL One toxicolog-

ical mechanismmdashdirect toxicity for the musclesmdashcould

be triggered by this myotoxin-alpha-like protein (16)

Whereas severe rhabdomyolysis is not uncommon in

Crotalus envenomations it is infrequent concerning

Sistrurus snake bites The first case of rhabdomyolysis

with consecutive renal failure after a pigmy rattlesnake

bite was published 1991 by Ahlstrom et al (1)

In summary the clinical effects of rattlesnake and

pigmy bites are caused by three groups of toxins

hemorrhagins are responsible for coagulation disorders

neurotoxins can lead to paralyses and rhabdomyolysis

develops due to myotoxins

Apart from symptomatic therapy of rattlesnake bites

two specific regimen exist On the one hand an

antivenom is available On the other hand surgical

treatment may be necessary A very comprehensive

review including all different aspects of snake anti-

venoms especially the risks and side effects of

antivenom treatment was published in Clinical Toxicol-

ogy only recently (23) In consent with these authors we

suggest the indication for the application of antivenom

to be very strict since there is a high probability of

developing hypersensivity reactions especially serum

sickness The figures of the development of serious

side effects of the antivenom vary between 10 and

more than 50 (923) In our opinion it should only be

applied in severe envenomation Antivenom therapy

should always be performed under intensive-care mon-

itoring The indications consist of increasing local ef-

fects like necrosis and a deterioration of the systemic

toxic effects such as the impairment of coagulational or

development of neurological symptoms Because of the

serious potential side effects a prophylactic application

Rattlesnake Bites in Europe 639

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

should be omitted Concerning the availability of snake

antivenom the situation is very heterogenous in Europe

most poison centers do not store the antivenom Usually

the antivenom is available in university hospitals but

only in a small number of poison centers In our opinion

this heterogeneity can affect the treatment of the pa-

tients retrospectively some of the patients who did not

get the antivenom should have been treated on the

other hand at least one patient who was treated did not

need the antivenom

Concerning surgical treatment the indication

should be strict as well the development of abscesses

or a threatening compartment syndrome are reasons for

surgery Severe local effects even circumscribed

necrosis are not necessarily an indication for surgery

Taking the potential side effects into account these

local symptoms can be treated very effectively by

antivenom The excision of the fangmark is discussed

controversially in literature a probable foreign body in

the wound can be an indication for surgical treatment

The experience concerning these envenomations is

limited in Europe but several studies from the United

States draw similar conclusions (8914)

In conclusion the indication for both antivenom

therapy and for surgical treatment following rattlesnake

bites should be very strict Increasing systemic effects

of the toxins are indications for antivenom therapy

Surgical treatment is necessary in cases of abscess or

compartment syndrome

REFERENCES

1 Ahlstrom NG Luginbuhl W Tisher CC Acute

anuric renal failure after pigmy rattlesnake bite

South Med J Jun 1991 84(6)783ndash785

2 Persson HE Sjoberg GK Haines JA Pronczuk de

Garbino J Poisoning severity score Grading of

acute poisoning J Toxicol Clin Toxicol 199836(3)205ndash213

3 Tu AT Preface Rattlesnake Venoms 1st ed New

York Marcel Dekker Inc 1982 V

4 Kass L Loop MS Hartline PH Anatomical and

physiological localization of visual and infrared

cell layers in tectum of pit vipers J Comp Neurol

Dec 15 1978 182(4 Pt 2)811ndash820

5 de Haro L Hayek-Lanthois M Jouglard J-P David

J-M Jouglard J Envenimations par serpents

exotiques bilan du centre anti-poison de Marseille

Bull Soc Herp Fr 1995 75ndash7651ndash566 de Haro L Pommier P Envenomation a real risk

of keeping exotic house pets Vet Hum Toxicol

August 2003 45(4)214ndash216

7 Bismuth C Chouvalidze N Baud F Soria C

Drouet L Tobelem G Defibrination Pure Apres

Morsure de Crotale Horridus La Presse Medicale

1983 291 15 janvier 12 N8 Shaw BA Hosalkar HS Rattlesnake bites in

children antivenin treatment and surgical indica-

tions J Bone Jt Surg Am Sep 2002 84-

A(9)1624ndash1629

9 White RR IV Weber RA Poisonous snakebite in

central Texas Possible indicators for antivenin

treatment Ann Surg May 1991 213(5)466ndash471

discussion 471ndash472

10 Ownby CL Colberg TR Li Q Presence of heat-

stable hemorrhagic toxins in snake venoms

Toxicon Aug 1994 32(8)945ndash954

11 Freitas MA Geno PW Sumner LW Cooke ME

Hudiburg SA Ownby CL Kaiser II Odell Citrate

is a major component of snake venoms Toxicon

Apr 1992 30(4)461ndash464

12 Scarborough RM Rose JW Hsu MA Phillips DR

Fried VA Campbell AM Nannizzi L Charo IF

Barbourin A GPIIb-IIIa-specific integrin an-

tagonist from the venom of Sistrurus m barbouri

J Biol Chem May 25 1991 266(15)9359ndash

9362

13 Minton SA Weinstein SA Protease activity and

lethal toxicity of venoms from some little known

rattlesnakes Toxicon 1984 22(5)828ndash830

14 Weber RA White RR IV Crotalidae envenoma-

tion in children Ann Plast Surg Aug 199331(2)141ndash145

15 de Haro L Envenimations Rev Prat Feb 15 200050(4)401ndash406

16 Bober MA Glenn JL Straight RC Ownby CL

Detection of myotoxin alpha-like proteins in

various snake venoms Toxicon 1988 26(7)

665ndash673

17 Foote R MacMahon JA Electrophoretic studies of

rattlesnake (Crotalus and Sistrurus) venom taxo-

nomic implications Comp Biochem Physiol B

1977 57(3)23

18 Mebs D Pohlmann S Von Tenspolde W Snake

venom hemorrhagins neutralization by com-

mercial antivenoms Toxicon 1988 26(5)453ndash

458

19 Gibbs HL Prior KA Weatherhead PJ Johnson

G Genetic structure of populations of the

threatened eastern massasauga rattlesnake Sis-

trurus c catenatus evidence from microsatellite

DNA markers Mol Ecol Dec 1997 6(12)1123ndash

1132

20 Lougheed SC Gibbs HL Prior KA Weatherhead

PJ A comparison of RAPD versus microsatellite

640 Schaper et al

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

DNA markers in population studies of the massa-

sauga rattlesnake J Heredity NovndashDec 200091(6)458ndash463

21 Assi AA Nasser H An in vitro and in vivo study

of some biological and biochemical effects of

Sistrurus Malarius Barbouri venom Toxicology

Sep 20 1999 137(2)81ndash94

22 Tan NH Ponnudurai G A comparative study of

the biological activities of rattlesnake (genera

Crotalus and Sistrurus) venoms Comp Biochem

Physiol C 1991 98(2ndash3)455ndash461

23 Lalloo DG Theakston RD Snake antivenoms J

Toxicol Clin Toxicol 2003 41(3) pp 277ndash290

317ndash327

Submitted January 14 2004

Accepted May 18 2004

Rattlesnake Bites in Europe 641

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

should be omitted Concerning the availability of snake

antivenom the situation is very heterogenous in Europe

most poison centers do not store the antivenom Usually

the antivenom is available in university hospitals but

only in a small number of poison centers In our opinion

this heterogeneity can affect the treatment of the pa-

tients retrospectively some of the patients who did not

get the antivenom should have been treated on the

other hand at least one patient who was treated did not

need the antivenom

Concerning surgical treatment the indication

should be strict as well the development of abscesses

or a threatening compartment syndrome are reasons for

surgery Severe local effects even circumscribed

necrosis are not necessarily an indication for surgery

Taking the potential side effects into account these

local symptoms can be treated very effectively by

antivenom The excision of the fangmark is discussed

controversially in literature a probable foreign body in

the wound can be an indication for surgical treatment

The experience concerning these envenomations is

limited in Europe but several studies from the United

States draw similar conclusions (8914)

In conclusion the indication for both antivenom

therapy and for surgical treatment following rattlesnake

bites should be very strict Increasing systemic effects

of the toxins are indications for antivenom therapy

Surgical treatment is necessary in cases of abscess or

compartment syndrome

REFERENCES

1 Ahlstrom NG Luginbuhl W Tisher CC Acute

anuric renal failure after pigmy rattlesnake bite

South Med J Jun 1991 84(6)783ndash785

2 Persson HE Sjoberg GK Haines JA Pronczuk de

Garbino J Poisoning severity score Grading of

acute poisoning J Toxicol Clin Toxicol 199836(3)205ndash213

3 Tu AT Preface Rattlesnake Venoms 1st ed New

York Marcel Dekker Inc 1982 V

4 Kass L Loop MS Hartline PH Anatomical and

physiological localization of visual and infrared

cell layers in tectum of pit vipers J Comp Neurol

Dec 15 1978 182(4 Pt 2)811ndash820

5 de Haro L Hayek-Lanthois M Jouglard J-P David

J-M Jouglard J Envenimations par serpents

exotiques bilan du centre anti-poison de Marseille

Bull Soc Herp Fr 1995 75ndash7651ndash566 de Haro L Pommier P Envenomation a real risk

of keeping exotic house pets Vet Hum Toxicol

August 2003 45(4)214ndash216

7 Bismuth C Chouvalidze N Baud F Soria C

Drouet L Tobelem G Defibrination Pure Apres

Morsure de Crotale Horridus La Presse Medicale

1983 291 15 janvier 12 N8 Shaw BA Hosalkar HS Rattlesnake bites in

children antivenin treatment and surgical indica-

tions J Bone Jt Surg Am Sep 2002 84-

A(9)1624ndash1629

9 White RR IV Weber RA Poisonous snakebite in

central Texas Possible indicators for antivenin

treatment Ann Surg May 1991 213(5)466ndash471

discussion 471ndash472

10 Ownby CL Colberg TR Li Q Presence of heat-

stable hemorrhagic toxins in snake venoms

Toxicon Aug 1994 32(8)945ndash954

11 Freitas MA Geno PW Sumner LW Cooke ME

Hudiburg SA Ownby CL Kaiser II Odell Citrate

is a major component of snake venoms Toxicon

Apr 1992 30(4)461ndash464

12 Scarborough RM Rose JW Hsu MA Phillips DR

Fried VA Campbell AM Nannizzi L Charo IF

Barbourin A GPIIb-IIIa-specific integrin an-

tagonist from the venom of Sistrurus m barbouri

J Biol Chem May 25 1991 266(15)9359ndash

9362

13 Minton SA Weinstein SA Protease activity and

lethal toxicity of venoms from some little known

rattlesnakes Toxicon 1984 22(5)828ndash830

14 Weber RA White RR IV Crotalidae envenoma-

tion in children Ann Plast Surg Aug 199331(2)141ndash145

15 de Haro L Envenimations Rev Prat Feb 15 200050(4)401ndash406

16 Bober MA Glenn JL Straight RC Ownby CL

Detection of myotoxin alpha-like proteins in

various snake venoms Toxicon 1988 26(7)

665ndash673

17 Foote R MacMahon JA Electrophoretic studies of

rattlesnake (Crotalus and Sistrurus) venom taxo-

nomic implications Comp Biochem Physiol B

1977 57(3)23

18 Mebs D Pohlmann S Von Tenspolde W Snake

venom hemorrhagins neutralization by com-

mercial antivenoms Toxicon 1988 26(5)453ndash

458

19 Gibbs HL Prior KA Weatherhead PJ Johnson

G Genetic structure of populations of the

threatened eastern massasauga rattlesnake Sis-

trurus c catenatus evidence from microsatellite

DNA markers Mol Ecol Dec 1997 6(12)1123ndash

1132

20 Lougheed SC Gibbs HL Prior KA Weatherhead

PJ A comparison of RAPD versus microsatellite

640 Schaper et al

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

DNA markers in population studies of the massa-

sauga rattlesnake J Heredity NovndashDec 200091(6)458ndash463

21 Assi AA Nasser H An in vitro and in vivo study

of some biological and biochemical effects of

Sistrurus Malarius Barbouri venom Toxicology

Sep 20 1999 137(2)81ndash94

22 Tan NH Ponnudurai G A comparative study of

the biological activities of rattlesnake (genera

Crotalus and Sistrurus) venoms Comp Biochem

Physiol C 1991 98(2ndash3)455ndash461

23 Lalloo DG Theakston RD Snake antivenoms J

Toxicol Clin Toxicol 2003 41(3) pp 277ndash290

317ndash327

Submitted January 14 2004

Accepted May 18 2004

Rattlesnake Bites in Europe 641

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y

DNA markers in population studies of the massa-

sauga rattlesnake J Heredity NovndashDec 200091(6)458ndash463

21 Assi AA Nasser H An in vitro and in vivo study

of some biological and biochemical effects of

Sistrurus Malarius Barbouri venom Toxicology

Sep 20 1999 137(2)81ndash94

22 Tan NH Ponnudurai G A comparative study of

the biological activities of rattlesnake (genera

Crotalus and Sistrurus) venoms Comp Biochem

Physiol C 1991 98(2ndash3)455ndash461

23 Lalloo DG Theakston RD Snake antivenoms J

Toxicol Clin Toxicol 2003 41(3) pp 277ndash290

317ndash327

Submitted January 14 2004

Accepted May 18 2004

Rattlesnake Bites in Europe 641

Clin

ical

Tox

icol

ogy

Dow

nloa

ded

from

info

rmah

ealth

care

com

by

Penn

Sta

te B

erks

Cam

pus

on 1

105

14

For

pers

onal

use

onl

y