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Scorpions are arthropods with a hard exoskeleton, two anterior pinching claws, and a tail ending with a bulbous enlargement. The poison gland and the stinger are located at the distal part of the tail. The tail is long and able to arch over the head, allowing the stinger to hit the prey grasped between the claws [1]. Scorpions are among the oldest creatures on earth. Their habitat is warm and arid areas, as reflected in their first mentioning in the Bible: “He led you through the vast and dreadful desert, that thirsty and waterless land, with venomous snakes and scorpions” [2]. The scorpion is a nocturnal animal that hibernates in winter and is active in the warm seasons [3].
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Middle East and North African
Yona Amitai
Epidemiology ......................................... 1
Biochemistry and Pathophysiology of Scorpion
Envenomation .................................... 2
Clinical Manifestations .............................. 4
Diagnosis and Laboratory Findings ................ 5
Treatment ............................................. 6
Antivenom Therapy . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Special Populations .................................. 11
Pregnant Patients . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Grading System for Levels of Evidence Supporting
Recommendations in Critical Care Toxicology,
2nd Edition ........................................ 12
References ............................................ 12
Scorpions are arthropods with a hard exoskeleton,
two anterior pinching claws, and a tail ending with
a bulbous enlargement. The poison gland and the
stinger are located at the distal part of the tail. The
tail is long and able to arch over the head, allowing
the stinger to hit the prey grasped between the
claws [1]. Scorpions are among the oldest crea-
tures on earth. Their habitat is warm and arid
areas, as reected in their rst mentioning in the
Bible: He led you through the vast and dreadful
desert, that thirsty and waterless land, with ven-
omous snakes and scorpions[2]. The scorpion is
a nocturnal animal that hibernates in winter and is
active in the warm seasons [3].
Scorpion sting is common and endemic in various
regions. Because most envenomations occur in
developing countries, where regular reporting
systems often are lacking, data on scorpion stings
in several countries are based on estimates. High
fatality rates were reported from scorpion enven-
omation from Saudi Arabia, Israel, Tunisia,
Egypt, and Iran in the 1960s and 1970s. In recent
years, there has been a marked reduction in mor-
tality, however, owing to the improvement in sup-
portive care and increased availability of
antivenom therapy.
In a report by Chippaux and Goyffon from
2008, the estimated annual number of scorpion
stings exceeded 1.2 million globally, with more
Y. Amitai (*)
Department of Management, Bar Ilan University,
Jerusalem, Israel
#Springer International Publishing Switzerland 2016
J. Brent et al. (eds.), Critical Care Toxicology,
DOI 10.1007/978-3-319-20790-2_104-1
than 3,250 deaths (0.27 %). Middle Eastern and
North African scorpion stings accounted for 42 %
of the global sting burden and a half of the fatal-
ities. The number of scorpion stings in the Middle
East and North Africa was estimated at 146,500
and 350,000, respectively [4]. The case-fatality
rates were estimated at 0.42 % and 0.52 %,
respectively, but these estimates are imprecise
due to incomplete information.
Scorpion species of medical importance in the
Middle East and Africa have been mainly reported
from Tunisia, Morocco, Egypt, Israel, Saudi Ara-
bia, Turkey, and Iran, though likely occur across
all countries in North Africa and the Middle East
[428]. Some of the main venomous scorpions,
their geographic distribution, and target organ
toxicities are listed in Table 1.
The main offending toxic scorpion in the Middle
East, Leiurus quinquestriatus is illustrated in Fig. 1.
Some of the major clinical series of scorpion
envenomations reported from Middle East and
North African countries are listed in Table 2.
Biochemistry and Pathophysiology
of Scorpion Envenomation
Scorpion venom is a complex mixture of muco-
polysaccharides, hyaluronidase, serotonin, hista-
mine, protease inhibitors, histamine releasers,
neurotoxins, and approximately 70 polypeptides.
Despite species differences, there are some simi-
larities in venom composition; this explains some
similarities among clinical manifestations in
envenomation sustained from scorpion stings
from different geographic locations [30].
Scorpion venom increases neuronal Na
by blocking inactivation of the Na
resulting in increased duration and amplitude of
the neuron action potential (Fig. 2). Consequently,
a voltage-gated channel opening is enhanced by
increased Ca
conductance at presynaptic nerve
bers, with increased release of neurotransmitters,
including acetylcholine [31,32]. The clinical
effects of this enhanced neural impulse transmis-
sion include muscle fasciculations, respiratory,
Table 1 Scorpion envenomation by species, regions, and characteristic toxicity
Scorpion species Geographic region
Hemolysis DIC, renal
failure cytotoxicity Reference
Leiurus quinquestriatus Middle East, Turkey +++ ++ [1420]
Androctonus crassicauda,
A. australis, A. mauretanicus
Middle East and North
Africa, Turkey, Iran
+++ ++ [511,20,
Buthus occtitanus North Africa +++ + [6]
Hemiscorpius lepturus Iran, Iraq + + ++ [23,
Fig. 1 The scorpion
Leiurus quinquestriatus
2 Y. Amitai
gastric, and pancreatic hypersecretion, and, occa-
sionally, bradycardia [33,34]. Parasympathetic
stimulation also may cause vascular dilation of
the penile arterioles supplying the corpus
cavernosus, resulting in priapism.
Scorpion venom also induces sympathetic
stimulation with excessive adrenergic discharge
[35]. The clinical effects of scorpion envenom-
ation may include parasympathetic and sympa-
thetic stimulation. The nonspecic signs of
tachycardia, tachypnea, hypothermia or hyper-
thermia, and leukocytosis are explained by cyto-
kine release (particularly, interleukin-6 [64] and
interleukin-1) and increased autonomic
Table 2 Reports on scorpion envenomation by regions, study population, setting, and case fatality rates
First author;
reference; years Setting and sample size
Case fatality
rate Comment
Goyffon [5],
Hospital, a few were
admitted; n=717
0.35 % All fatalities <15 year old
Abroug [7],
Hospital, controlled study
n=825: age >10 year old
0.24 % Only 18 % had systemic envenomation
Bouaziz [9],
ICU, n=951; 72 % <16
year old
7.5 % 81 % had severe envenomation
Ghalim [11],
Prospective, hospitals
Not reported 10 % has systemic envenomation
Farghly [12],
Prospective, hospital
n=302; 78 % <18 year old
8 % 19 % with congestive heart failure
Mohamad [13],
Retrospective, hospital:
n=111; <16 year
18 % 53 % had severe systemic envenomation
Amitai [14],
Retrospective, hospital;
n=51; <13 year
3.9 % 29 % had severe systemic envenomation
Sofer [15];
Retrospective, historical
control; 104 children in PICU,
52 with AV
1.9 % Treatment group 19859 controls in
Time of AV M=1.56 h after sting
el-Amin [17]
Saudi Arabia;
Retrospective; hospitalized
children; n=780
reduced from
4.8 % to 0 %
Antivenom was very effective
Bosnak [20],
Retrospective hospitalized
PICU; <15 years; n=45
4.4 % All patients received antivenom and
Konca [22],
Retrospective; hospitalized
<17 years; n=80
1.2 % 57 % with severe envenomation
Pipelzadeh [23],
Retrospective, hospitalized
N=354; 40 % <10 years
8.4 % 90 % of the fatalities got antivenom >12 h
after the sting. Most of severe cases due to
H. lepturus.
[24], Iran
Retrospective; emergency
departments; n=12,150
0.02 % 74.5 % were mild
Dehghani [27],
Review; retrospective
0.46 %
Middle East and North African Scorpions 3
neurotransmission. In a canine model, injection of
venom from the yellow scorpion (Leiurus
quinquestriatus) resulted in an early stage of
increased cardiac output and hypertension,
followed by a second stage of reduction in cardiac
output [37]. These two stages may reect an initial
catecholamine discharge with a subsequent stage
of catecholamine depletion. The mechanism of
cardiotoxicity in scorpion envenomation is multi-
factorial, beginning with catecholamine
overstimulation, causing hypertension and a tran-
sient phase of increased contractility. There is a
diminished systolic performance in addition to the
catecholamine effect. The combination of myo-
cardial ischemia, excessive catecholamine effect,
cardiac arrhythmia, and increased oxygen demand
may result in acute myocardial infarction [38].
Respiratory failure, caused by pulmonary
edema, is a common complication of severe scor-
pion envenomation. The pulmonary edema has a
cardiogenic and noncardiogenic component. The
latter is thought to occur as a result of increased
vascular permeability induced by release of vaso-
active substances [38]. Central nervous system
involvement is more frequent in children with
severe envenomation. In the case of L.
quinquestriatus sting, central nervous system
effects are explained partially on the basis of
hypertension, causing hypertensive encephalopa-
thy, and may respond to antihypertensive therapy
(prazosin) [39]. Central nervous system
manifestations, such as agitation, hyperthermia,
hypertonus, seizures, and coma [14,38,40], also
occur, however, in the presence of normal blood
pressure, suggesting a more direct central mecha-
nism of toxicity [38]. Intraventricular injection of
extremely small doses of toxic L. quinquestriatus
venom to rabbits (1/500 to 1/100 of the intrave-
nous lethal dose) caused complex neurotoxicity
with restlessness, tremors, and convulsions [38].
Clinical Manifestations
The severity of scorpion envenomation varies with
the scorpions species, age, and size, but clinical
severity tends to be greater in children. As a general
rule, venomous scorpions with thin claws are more
toxic than scorpions with thick claws. Clinical
severity ranges from local pain to encephalopathy
and potentially fatal cardiotoxicity.
In most cases, adults stung by scorpions expe-
rience only local symptoms and signs consisting
of pain, erythema, pruritus, edema, and paresthe-
sias [34,41], occasionally involving the extremi-
ties and the perioral area [41]. Local skin necrosis
has been documented only from stings of
Hemiscorpius lepturus in Iran and may occasion-
ally be severe and accompanied by hemlolysis and
complicated by renal failure and disseminated
intravascular coagulopathy [23,29]. This is a
unique and quite atypical form of scorpion
3 Å by 5 Å
Toxins bind at this end
Enzymes inactivate
and scorpion toxin
blocks at this end
Local anesthetics
bind in pore P
1 2
Fig. 2 Schematic
representation of the
voltage-gated channel in a
neuron showing the site of
scorpion toxin binding. The
channel is roughly a
0.3 mm 0.5 nm
rectangular hole formed by
four of the transmembrane
helices within this subunit
(From Brody TM, Garrison
JC: Sites of action:
Receptors. In Brody TM,
Larner J, Minneman KP
(eds): Human
Pharmacology: Molecular
to Clinical, 3rd ed. St.
Louis, Mosby, 1998, p 18.
With permission)
4 Y. Amitai
envenoming, not seen following stings by other
medically important scorpions, which can broadly
be characterized as neuroexcitatory, as opposed to
the dermonecrotic and hemolytic venom of
Hemiscorpius lepturus.
For the numerous neuroexcitatory scorpion spe-
cies, systemic envenoming reects stimulation or
depression of the central nervous system and stim-
ulation of the sympathetic, parasympathetic, and
skeletal motor nervous systems. Skeletal motor and
parasympathetic stimulation is manifest mainly as
tongue and muscle fasciculation, gastric and pan-
creatic hypersecretion, and occasionally bradycar-
dia [14,33,42]. Salivation, abdominal pain,
nausea, and vomiting are common and may be
attributed to stimulation of salivary glands and to
pancreatitis [42]. Parasympathetic stimulation also
may cause priapism, even in young boys [14,43].
In the cardiovascular system, the increased
sympathetic tone prevails, as reected by the
high incidence of tachycardia and hypertension
(72 % and 58 %) and the much lower incidence
of bradycardia and hypotension (14 % and 5 %)
in victims of scorpion envenomation [34]. In a
report of 386 children with scorpion stings from
Saudi Arabia, tachycardia occurred in 32 % of
children and bradycardia in 0.77 % [43].
Most scorpions with the potential to cause
human envenomation in the Middle East and
North Africa exert cardiotoxicity and
neuroexcitatory neurotoxicity (see Table 1). A
grading system for scorpion envenomation has
been developed in Tunisia, consisting of three
classes. This grading system has been further
developed by a Consensus Group of experts in
2011, for the purpose of facilitating development
of international clinical studies.
The three classes are: Class 1local manifes-
tations; Class 2 minor manifestations (non-life-
threatening), and Class 3 severe manifestations
(life-threatening) [44]. The details of this classi-
cation with the specic symptoms are specied in
Table 3.
A simplied grading system, based on clinical
grade and focused on treatment, has been
published by Isbister and Bawaskar (Table 4),
though presumably largely based on experience
with scorpion sting in India [45].
Envenomation by the main venomous scorpion
species in North Africa and the Middle East (L.
quinquestriatus and Androctonus crassicauda)
and India (Hottentotta tamulus) has a similar clin-
ical course. Effects of mild envenomation are
agitation, tachycardia, and sweating. In more
severe cases, particularly in young children, addi-
tional symptoms include vomiting, abdominal
pain, salivation, dehydration, priapism, extreme
agitation, generalized erythema, muscle rigidity
and twitching, tremor, seizures, coma, pupillary
changes (miosis, mydriasis, or anisocoria), hyper-
thermia, tachyarrhythmia or occasionally
bradyarrhythmia and A-V Block, hypertension
(less often hypotension), cardiac and respiratory
failure, and death [14,34,43]. Idiopathic dilated
cardiomyopathy was found to be eight times more
frequent in patients with a past history of scorpion
sting in India, despite apparent complete recovery
from the acute envenomation [46].
Diagnosis and Laboratory Findings
The diagnosis of scorpion envenomation is made by
the characteristic clinical presentation of the patient
in an area in which scorpions are endemic. Occa-
sionally the scorpion is seen, or the sting may be
witnessed, though in nearly all cases the initial pain
of the sting helps assure the diagnosis. The excep-
tion is dermonecrotic envenoming by Hemiscorpius
lepturus in Iran and adjacent countries, where the
sting may be initially painless and unnoticed, with
later development of local skin damage and, in
more severe cases, systemic envenoming character-
ized by intravascular hemolysis, DIC, shock, and
sometimes multiorgan failure.
Laboratory abnormalities have been reported
mainly from scorpion stings from the Middle
East, North Africa, and India. Hyperglycemia and
leukocytosis are nonspecic but common [14,20,
47]. Cardiac ischemia is expressed by transient
elevation of cardiac enzymes [38,48] and electro-
cardiograms with depressed or elevated ST seg-
ment, Q waves in leads I and aVL, prolonged
intervals, and peaked T waves [38]. Cardiac
dysfunction is evidenced on echocardiography as
diminished global wall motion with decreased
Middle East and North African Scorpions 5
systolic left ventricular performance and dimin-
ished ejection fraction [4951]. Left ventricular
dysfunction also has been shown by cardiac radio-
nuclide scan [50]. Transient elevation of pancreatic
enzymes has been reported [42]. For Hemiscorpius
lepturus stings in Iran there may be laboratory
evidence of hemolysis, coagulopathy, renal failure,
and other secondary effects.
Numerous treatments have been recommended
for scorpion envenomation, including antivenom,
prazosin, inotropic agents, atropine, vasodilators,
and benzodiazepines (Table 4). However, the evi-
dence for the effectiveness of most treatments is
variable, and types of treatment appear to vary
according to region [45].
As a general approach, the following recom-
mendations can be made:
First aid and prehospital treatment:
1. Cleansing the sting site with alcohol or soap.
2. Reducing the spread of the venom before arriv-
ing at a medical facility is crucial. Several
reports emphasize the critical effect on the out-
come of delay in time of arrival of the victim to
medical facilities [11,15,38]. This is explained
by the rapid spread of the venom [52]. To reduce
lymphatic spread of the venom, immobilize the
stung limb (Grade III recommendation).
3. Application of an elastic bandage or gauze ban-
dage with light pressure on the sting site may
reduce the spread of the venom. This pressure-
immobilization techniqueis endorsed by the
National Health and Medical Research Council
of Australia to reduce lymphatic spread in toxic
snake bites [53]. It is logical to also use such
technique for venomous scorpions. Increased
venom concentration at the sting site should
not be a problem in envenomation by most
scorpion species as local necrosis is rare with
scorpion stings by most scorpion species.
Applying this technique is not recommended
Table 3 Modified proposed classification of scorpion stings
manifestations Minor manifestations (non-life-threatening)
Severe manifestations (life threatening)
Presence of at least one of the following
Pain Agitation/restlessness/
Priapism Cardiogenic failure
Local paresthesia Altered mental status Pupillary
GCS score 6 (in absence of sedation)
Rash Arthralgia Rhinorrhea Paralysis
Ataxia Salivation Respiratory failure
Dry mouth Seizures Paralysis
Dystonia Stridor
Fasciculation Sweating
Gastrointestinal symptoms Tachycardia
Generalized paresthesias Temperature
Hematuria Urinary retention
Headache Wheezing
Muscular cramps
Modied from Khattabi et al. [44]
6 Y. Amitai
in stings by Hemiscorpius lepturus in Iran and
Iraq, which tends to cause local necrosis [23,
29]. Application of tourniquet, cauterization, or
incision and drainage are contraindicated for all
scorpion stings. An Australian study of venom-
ous snake bites without local necrosis in a rat
model showed that local application of nifedi-
pine, lidocaine, and NO releasing ointments
markedly reduced the spread of venom from
the sting site [53]. However, there are no
published data for such treatments in humans.
4. Transport the victim to a medical facility as
soon as possible, particularly when the victim
is an infant or small child. If it is known or
suspected that the scorpion is capable of
envenoming humans, all victims of sting
should be transported to a hospital or clinic.
5. When an elastic bandage has been applied, it
should be removed under observation when the
victim has arrived at a medical facility.
6. Analgesics (acetaminophen, ibuprofen) are
recommended for pain relief [45]. Topical
application of lidocaine may also be helpful.
7. In most cases, adults stung by scorpions do not
develop a systemic envenomation syndrome.
Close observation outside of a health care facil-
ity for 26 h is sufcient in these cases. In
regions where cardiotoxic scorpions are
endemic (see Table 1), an electrocardiogram
should be performed.
Hospital admission and in-hospital treatment:
1. A clinical score predicting the need for hospi-
talization in scorpion envenomation was devel-
oped by Nouira et al., from Tunisia, based on a
prospective study in 868 patients with scorpion
envenomation with a validation group of
435 patients. The following variables were
strong predictors for admission: priapism,
vomiting, hypertension (>160 mmHg),
administration of corticosteroids before arrival
to emergency department, delay (>30 min) to
emergency department arrival, hyperthermia,
and tachycardia [8].
2. In cases of systemic envenomation, the princi-
ples of management are observation, cardiac
monitoring, supportive treatment with intrave-
nous uids and electrolytes, sedatives and
analgesics, and cautious use of cardiovascular
agents, including vasodilators, adrenergic
antagonists, or calcium channel blockers, in
the hypertensive phase. Sofer and colleagues
[15] advocated the use of hydralazine or nifed-
ipine. Bawaskar and Bawaskar [36] found
prazosin to be safer and more effective than
nifedipine in their patients stung by the Indian
scorpion, Hottentotta tamulus and recommended
using prazosin alone in patients with hyperten-
sion and tachycardia from scorpion sting. In a
controlled study, these authors reported lower
complication rates (no fatalities) in patients
treated with nifedipine or supportive care alone
(fatality rates of 35 % and 25 %, respectively).
However, subsequent studies by these authors
have indicated that antivenom is the most effec-
tive treatment.
3. Elatrous and coworkers from Tunisia reported
the efcacy of dobutamine infusion at 720 μg/
kg/min in 19 patients with severe scorpion
Table 4 Clinical grade and treatment of scorpion stings
Grade Effects Treatment
1 Local effects only Analgesia, local
2 Autonomic
Antivenom, prazosin
Agitation and
3 Pulmonary edema Admission to intensive
care unit, noninvasive
or mechanical
ventilation, antivenom
Hypotension and
cardiogenic shock
(associated with
4 Multiorgan failure,
including coma,
seizures, and
end-organ damage
caused by
Supportive care,
ventilation, inotropes
(e.g., dobutamine),
Adapted from Isbister and Bawaskar [45]
Middle East and North African Scorpions 7
envenomation and acute pulmonary edema, of
whom ten also had severe hypotension. In these
patients, cardiac output, blood pressure, tissue
oxygenation, and clinical outcome improved
signicantly, but there were two fatalities
[54]. Antiarrhythmics, such as lidocaine, may
be required [38]. In an experimental envenom-
ation by L.quinquestriatus in rabbits, lidocaine
infusion signicantly attenuated venom-
invoked effects and reduced mortality [55].
Use of sedatives to reduce anxiety and agita-
tion has an important role in the treatment of
symptomatic patients. Benzodiazepines are used
for sedation [45]. At the Hadassah University
Hospital, Mt. Scopus, Jerusalem, we have used
diazepam or midazolam at doses titrated to control
agitation and anxiety in children with scorpion
envenomation with good response. Steroids have
no role in the treatment of scorpion
envenomation [56].
Antivenom Therapy
Specic antivenom therapy has been used for sev-
eral decades. Most antivenom preparations consist
of animal serum (mainly equine) and are immuno-
globulin F(ab)
fragments. The types of scorpion
antivenom used in each country were summarized
by Bahloul et al. in 2013 [47]. Those relevant to
Middle Eastern and North African appear in
Tab l e 5.
The antivenom currently used in Israel is
SCORPIFAV, a polyvalent scorpion antivenom
against A. australis, B. occitanus, and L.
quinquestriatus, produced by Sano-Pasteur
Numerous reports exist on the clinical use of
specic antivenom preparations from Middle
Eastern and North African countries [7,11,
Due to ethical limitations, most studies are
retrospective, observational, or historical controls.
There are only a few prospective, randomized,
controlled studies [6,7]. Reports on antivenom
therapy are summarized in Table 6. Of the seven
reports summarized there, ve concluded that
antivenom is effective [11,16,17,38,57], two
concluded that antivenom is not effective [7,15],
and one gave data only on safety and did not
report efcacy [43]. The two studies reporting a
lack of antivenom efcacy were controlled, and
one was randomized controlled. However, the
main limitation was that 82 % of the patients
had only local signs of envenomation (grade 1)
and only 1 % of patients in both groups had life-
threatening envenomation [7,57]. A meta-
analysis of controlled studies by Abroug
et al. concluded that antivenom for scorpion
Table 5 The types of scorpion antivenom used in Middle
Eastern and North African countries (Adapted from
Bahloul et al. [47])
Antivenom Species Country
australis garzonii,
B. occitanus
tunetanus, and
Tityus serrulatus
Puried polyvalent
serum (equine)
Androctonus aeneas
Scorpio marus
Buthus occitanus
antivenom (Pasteur
Institute of Algeria)
Bivalent scorpion
antivenom (Institut
Pasteur, Tunis,
A. australis and
B. occitanus
crassicauda, Buthus
arenicola, Butus
mimax, Buthus
occitanus, Leiurus
hebreus, and
A. amoreuxi
8 Y. Amitai
envenomation is ineffective [58]. However, the
main weight of randomized controlled studies in
this study was given to the original study of these
authors, which had the largest number of patients
[7] and affected the overall result. In a recent
review of scorpion envenomation by Isbister and
Bawaskar, the authors conclude: Although the
evidence in favor of antivenom is heterogeneous,
given the small sample size of the trials with
positive results and the different scorpion species
across studies, the reports, when taken together,
suggest that administration of antivenom after a
sting is of some benet[45].
Of note, antivenom for the scorpion
Centruroides sculpturatus from Southern United
States and for the Indian scorpion Hottentotta
tamalus were shown to be effective in randomized
controlled studies [45] (Grade I evidence).
Table 6 Published studies on antivenom efficacy in scorpion envenomation in the Middle East and North Africa
Study; region; years;
scorpion species
Study design; sample
type; dose;
and route
Results and
conclusion Comment
Sofer et al. [15];
Israel; 19851992;
historical control;
104 children in PICU,
52 with AV
515 mL; IV
No effect;
emphasis on
Treatment group in 19859;
Controls in 198992
Time of AV
M=1.56 h after sting
Ismail [16,38]; Saudi
Arabia; 19911992;
Androctonus, Leiurus
multicenter; 24,000
5 mL; IV
reduced from
46.8 % to
<0.05 %
Efcacy requires prompt IV
infusion and large dose
el-Amin et al. [17];
Saudi Arabia;
19881994; Leiurus
780 hospitalized
children and children
treated as outpatients
5 mL; IV
reduced from
4.8 % to 0 %
Very effective
Gajre and Dammas
[43]; Saudi Arabia;
19911995; Leiurus
182 children treated,
90 % symptomatic
(1020 mL for
patients); IV
Efcacy not
reactions in
13.7 %, severe
in 1 %
Restrict AV use to patients
with systemic envenomation
Abroug et al. [7];
Tunisia; 19941995;
australis, Buthus
825 patients >10 year
old, 412 treated
bivalent AV;
20 mL; IV
No effect; four
(1 %)
The antivenom was not
highly specic[57]82%of
patients had only local signs
and only 1 % of patients had
Kriet al. [6];
Tunisia; 19931997;
australis, Buthus
147 severely
envenomed children,
12 doses IV or IM or
no AV
bivalent AV,
530 mL; IV
AV given IV
effective; IM
not effective
Ghalim et al. [11];
Morocco; 1997;
mauretanicus, Buthus
275 patients
bivalent AV,
210 mL; IV
Effective Prompt use and large dose
AV antivenom, PICU pediatric intensive care unit
Some patients received 25 mL of antivenom, and some received 1 mL. In those who received the higher dose, there was
a higher degree of circulating venom depth
Middle East and North African Scorpions 9
Ismail [16,38] from Saudi Arabia reported
robust data on 24,000 patients with scorpion
envenomation treated by a national protocol.
Thousands of these patients were treated with
antivenom, with a reduction in the fatality rate
from 4 % to 6.8 % to less than 0.05 %. Among
780 children, the use of antivenom therapy
resulted in reduction of mortality from 4.8 % to
In Iran, there are trials to prepare a specic
antivenom for envenomation by the scorpion
Hemiscorpius lepturus, which so far were suc-
cessful only in an animal model [59]. However,
this antivenom is currently used in clinical prac-
tice in Iran.
Important points regarding the optimal use of
antivenom can be inferred from these reports, as
1. Because of regional variations in scorpion spe-
cies and specic antivenom preparations,
always obtain the advice of local experts (i.e.,
poison information centers, medical toxicolo-
gists, or treatment centers with expertise in the
eld of scorpion envenomation).
2. Reserve antivenom preparations for patients
with systemic toxicity. A suggested guideline
for treatment with antivenom is the appearance
of two or more of the signs and symptoms of
systemic envenomation listed in the box below
or the occurrence of one of the following:
arrhythmia, hypertension, hypotension, sei-
zures, coma, and pulmonary edema (Grade
II-2 evidence).
3. When indicated, give antivenom promptly
after onset of systemic signs or symptoms. In
the event of a rash appearing during antivenom
administration, decrease the infusion rate, add
intravenous antihistamine, and continue the
antivenom infusion, with caution and standby
intravenous epinephrine and airway manage-
ment equipment.
4. Administer antivenom intravenously only. The
intramuscular route is not effective, likely due
to the slow absorption and distribution of the
large antibody molecules from the intramuscu-
lar injection site [6].
5. The volume required depends on the prepara-
tion and the initial and subsequent responses to
treatment but may vary from 6 to 10 mL in
severe cases. Always consult with local experts
about the proper preparation, dose, and precise
instructions about how to administer the anti-
venom. The antivenom is diluted in 50 mL of
normal saline and administered intravenously
starting with a slow infusion rate and increasing
gradually. Skin testing generally is not
performed because when antivenom is deemed
necessary, there should not be a further delay in
its administration and there is no evidence indi-
cating reliability of such testing but ample evi-
dence of the potential hazard. The safety of
specic scorpion antivenom (i.e., low likelihood
of anaphylactic or anaphylactoid reaction)
given in various geographic locations is consid-
ered to be generally satisfactory [14,38]. This
safety is related to the low protein content of the
antivenom. Paradoxically, the theoretical likeli-
hood of patients with severe envenomation
developing an anaphylactoid reaction is lower
than that of patients with mild envenomation
because severe venom toxicity causes the
release of massive amounts of catecholamines,
inhibiting mast cell degranulation [60].
6. The dose should not vary with the age or weight
of the patient because it should be directed at
neutralizing a given amount of venom intro-
duced by the scorpion into the patientsbody.
At the Hadassah Hospitals, we have used anti-
venom therapy to treat more than 50 children
with systemic scorpion envenomation. In many
instances, an impressive reversal of signs and
symptoms was observed immediately after anti-
venom administration. This specicantivenom
is the only one available in Israel; however, it
has been reported also to be effective in the case
of envenomation by another (nonhomologous)
scorpion species, A. crassicauda [61]. The
explanation of this effect is related to the simi-
larity in venom composition between these two
scorpion species.
7. Patients who receive antivenom should be
followed at home for the next few days. If
serum sickness occurs, antihistamines or a
10 Y. Amitai
short course of oral steroids should be given
according to the severity of symptoms [62].
8. Advances in supportive care and antivenom
therapy have markedly improved the outcome
of patients treated for scorpion envenomation.
Indications for ICU Admission
in Neuroexcitatory Scorpion Envenomation
Infants and young children (<5 years old)
Anyone with systemic manifestations
consisting of two or more of the following:
Cardiovascular: tachycardia/bradycardia,
hypertension/hypotension, arrhythmia
Neurologic: agitation, lethargy, coma, tremor,
hypertonicity, seizures, opisthoclonus, par-
esthesia (other than at the sting site)
Respiratory: tachypnea, respiratory distress,
stridor, pulmonary edema
Dermatologic: sweating, ushed skin, goose
Laboratory: electrocardiogram abnormalities,
elevated myocardial enzymes, echocardio-
gram evidence of cardiac wall dysfunction
(reduced contraction)
One of the following: arrhythmia, hypertension
(new onset), hypotension, seizures, leth-
argy, coma, pulmonary edema, electrocar-
diogram or echocardiogram abnormalities,
increased myocardial enzymes CKMB,
Criteria for ICU Discharge in Neuroexcitatory
Scorpion Envenomation
Infants and young children (<5 years old)
lack of signs or symptoms of systemic enven-
omation for 6 h and normal electrocardiogram
Others resolution of systemic manifesta-
tions of scorpion envenomation for 3 h and no
new abnormalities on electrocardiogram
Special Populations
Pregnant Patients
Data are insufcient to make conclusions about
the safety of antivenom administration in preg-
nant women. However, in general there is no
evidence antivenom is harmful in pregnancy, par-
ticularly compared to signicant systemic
envenoming, therefore pregnancy should not be
considered a contraindication for antivenom treat-
ment. As for poisoning by other toxins, indica-
tions for treatment should be guided by maternal
clinical state.
Key Points in Scorpion Envenomation
1. Venomous scorpions exist in different
regions, usually in warm climates, and are
active in the warm season, particularly
after dark.
2. Because of marked geographic variations in
scorpion species and their toxicity, the cli-
nician always must consult with local
experts about treatment and administration
of antivenom.
3. As a rule, venomous scorpions with thin
claws are more toxic than scorpions with
thick claws.
4. Young children are at greater risk for severe
envenomation after a sting.
5. When antivenom is indicated, the dose
should be similar in children and adults.
6. After being stung, it is helpful if the patient
can catch or take a photo of the scorpion, for
7. In contrast to bee stings, scorpions excrete
only a small fraction of their venom in one
sting and could cause severe toxicity imme-
diately in repetitive stings [63].
8. After being stung, the patient should not
run. Immobilization of the affected limb is
important to slow venom distribution.
9. Incision and drainage at the site of the sting
is contraindicated.
Middle East and North African Scorpions 11
Grading System for Levels of Evidence
Supporting Recommendations
in Critical Care Toxicology, 2nd Edition
I. Evidence obtained from at least one properly
randomized controlled trial.
II-1. Evidence obtained from well-designed con-
trolled trials without randomization.
II-2. Evidence obtained from well-designed
cohort or case-control analytic studies, pref-
erably from more than one center or research
II-3. Evidence obtained from multiple time series
with or without the intervention. Dramatic
results in uncontrolled experiments (such as
the results of the introduction of penicillin
treatment in the 1940s) could also be
regarded as this type of evidence.
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14 Y. Amitai
... effectiveness of antivenoms against envenoming by scorpions has not been formally demonstrated by clinical trials in Arab countries of the Middle East. However, outside the region, antivenoms have proved effective (Amitai, 2017). In Arizona, USA, children stung by Centruroides sculpturatus who were treated with Instituto Bioclon Centruroides antivenom showed more rapid resolution of symptoms and required less midazolam sedation than those given placebo (Boyer et al., 2009). ...
The twelve Arab countries of the Middle East are inhabited by 117 species of scorpions of varying medical importance within six families. Scorpion stings are a very common occurrence throughout the region. Twenty-two scorpion species are considered to be dangerously venomous, causing potentially life threatening stings. Accessible literature in English and Arabic on scorpions, scorpion stings and available antivenoms was reviewed to document the scorpion fauna and scorpion stings in each country. Saudi Arabia, Iraq and Jordan report the highest numbers of stings and envenomings. Clinically, the most important toxins in Old World scorpion venoms are α-toxins that target voltage-gated sodium (Nav) channels at neurotoxin binding site 3, causing sympathetic excitation and the endogenous release of catecholamines that is responsible for transient, but life-threatening myocardial damage.Most victims of scorpion stings suffer severe local pain, but a few, especially children, develop systemic envenoming which, in the case of most Middle Eastern buthid species, such as Androctonus and Leiurus species, is dominated by the cardiovascular and respiratory consequences of hypercatecholinaemic myocarditis. Other syndromes include paralysis (Parabuthus leiosoma), coagulopathy (Nebo hierichonticus and Hemiscorpius species), and local tissue damage, haemolysis and acute kidney injury (H. lepturus). Early antivenom treatment is recommended but its value remains controversial. However, intensive care, with the ancillary use of vasoactive drugs such as prazosin and dobutamine, has proved effective.
On the road ahead for Egypt, the formidable obstacle is a two-headed monster: character and leadership. Now, after two revolutions, it is time to analyze this monster. Egypt must deal with this as success in development is simply not possible without first slaying this monster. As Egypt embarks on its immediate future, targeting its immediate political, economic, and social priorities, it must not overlook the crucial objective of determining the character of the nation, and the responsibility of its leadership. This is a prerequisite that if not met will delay further progress and development.
Social unrest may reflect a variety of factors such as poverty, unemployment, and social injustice. Despite the many possible contributing factors, the timing of violent protests in North Africa and the Middle East in 2011 as well as earlier riots in 2008 coincides with large peaks in global food prices. We identify a specific food price threshold above which protests become likely. These observations suggest that protests may reflect not only long-standing political failings of governments but also the sudden desperate straits of vulnerable populations. If food prices remain high, there is likely to be persistent and increasing global social disruption. Underlying the food price peaks we also find an ongoing trend of increasing prices. We extrapolate these trends and identify a crossing point to the domain of high impacts, even without price peaks, in 2012–2013. This implies that avoiding global food crises and associated social unrest requires rapid and concerted action.
Full-text available
The objective of our consensus process was to develop a unique classification of the natural history of scorpion stings and their clinical signs and symptoms. The technique used was an adapted Delphi approach completed by a nominal group meeting. Researchers included in a study received a questionnaire in which we listed all terms used in published studies to characterize clinical consequences of scorpion stings and all signs and symptoms belonging to each class. For each term, experts had to judge the relevance for classifying clinical consequences of scorpion stings and state whether they agreed with the terminology; they could also propose new terms or classes. For each sign or symptom, they had to choose in which class it belonged and also propose if any other sign or symptom should be added. Sixteen researchers participated. Consensus was reached to include four classes: local manifestations; minor systemic manifestations; major systemic manifestations; lethal envenomation. Signs and symptoms associated with each class were defined. A second Delphi round is planned to define indicators to follow the epidemiological situation within and across countries and to develop recommendations for an optimal management of scorpion envenomations. These consensus-based tools should facilitate development of international clinical studies.
Full-text available
Scorpion stings and envenomation are of clinical importance worldwide, and although most stings cause only local effects, severe envenomation that causes either excessive autonomic activity and cardiovascular toxic effects or neuromuscular toxic effects results in illness and, in the case of children, in death. The specific treatment is the administration of antivenom combined with symptomatic and supportive treatment, including prazosin and dobutamine in patients with cardiovascular toxic effects and benzodiazepines when there is neuromuscular involvement.
Full-text available
This study examines the use of topical pharmacological agents as a snakebite first aid where slowing venom reaching the circulation prevents systemic toxicity. It is based on the fact that toxin molecules in most snake venoms are large molecules and generally first enter and traverse the lymphatic system before accessing the circulation. It follows on from a previous study where it was shown that topical application of a nitric oxide donor slowed lymph flow to a similar extent in humans and rats as well as increased the time to respiratory arrest for subcutaneous injection of an elapid venom (Pseudonaja textilis, Ptx; Eastern brown snake) into the hind feet of anaesthetized rats. The effects of topical application of the L-type Ca(2+) channel antagonist nifedipine and the local anesthetic lignocaine in inhibiting lymph flow and protecting against envenomation was examined in an anaesthetized rat model. The agents significantly increased dye-measured lymph transit times by 500% and 390% compared to controls and increased the time to respiratory arrest to foot injection of a lethal dose of Ptx venom by 60% and 40% respectively. The study also examined the effect of Ptx venom dose over the lethal range of 0.4 to 1.5 mg/kg finding a negative linear relationship between increase in venom dose and time to respiratory arrest. The findings suggest that a range of agents that inhibit lymphatic flow could potentially be used as an adjunct treatment to pressure bandaging with immobilization (PBI) in snakebite first aid. This is important given that PBI (a snakebite first aid recommended by the Australian National Health and Medical research Council) is often incorrectly applied. The use of a local anesthetic would have the added advantage of reducing pain.
All cases of scorpion stings (2240) that attended all primary health care centres and hospitals in Hail region, Saudi Arabia, from 1 June 1994 to 31 August 1995 were recorded and analysed. The incidence of scorpion stings and treatment by antivenom were studied. A total incidence of 1.87% was found for the 15-month period. The severity of symptoms and signs were marked among infants. Guidelines for the management of scorpion stings are suggested and the importance of local treatment of stings affecting infants and preschool children is emphasized.
Objectives: To study the clinical aspects and frequency of scorpion stings in Riyadh region of Saudi Arabia. Methods: Clinical aspects and frequency of scorpion sting cases reporting to 2 referral hospitals in the Riyadh region of Saudi Arabia were analyzed during May 2006 to April 2008. Data on demographic status, date and time of sting, sting site, scorpion color, clinical manifestations, and treatment were collected. Results: A total of 391 cases of scorpion stings were recorded from the 2-referral hospitals, 248 (63.4%) of were men and 143 (36.6%) were women. The 21-30 years age group was the worst affected, followed by 31-40 years, 11-20 years, and <10 years age groups. Larger number of stings occurred during the summer months, at nights, and on distal limbs. Most of the patients reached the hospital within one hour of the sting. The yellow scorpions were responsible for a larger number of stings than the black scorpions. Seventy-five percent of the patients showed local signs and symptoms and 25% demonstrated systemic manifestations of poisoning. Most of the patients were treated with antivenom. Conclusion: The high prevalence of scorpion stings largely with mild signs/symptoms and without any mortality suggests the predominance of weak venomous scorpion species in the Riyadh region. Therefore, the protocol of managing scorpion-sting patients with antivenom irrespective of the intensity of manifestations warrants a detailed review.
This epidemiological review was carried out to display the magnitude and the geographic distribution of scorpion envenomation in Iran with focus on the southwestern region of Iran, particularly. The Iranian recognized scorpions belonging to two families, including Buthidae and Scorpionidae. Buthidae family consists of 14 genuses, 26 species, and 18 sub-species, while Scorpionidae family has three genuses and four species. The lack of basic knowledge, including the geographical distribution, clinical manifestations, and specific treatments related to scorpiofauna justifies such multidisciplinary studies. The venom of two endemic Iranian scorpions, including Hemiscorpius lepturus (H. lepturus) and Odonthubuthus doriae (O.doriae) have considered as an effective source of new neurotoxin peptides for the further development of physio-pharmacological probes and designing the clinical trials. Such epidemiological information may improve the determinants of Iranian scorpion stings in order to plan and implement effective public health intervention. © 2014 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services.
This epidemiological review was carried out to display the magnitude and the geographic distribution of scorpion envenomation in Iran with focus on the southwestern region of Iran, particularly. The Iranian recognized scorpions belonging to two families, including Buthidae and Scorpionidae. Buthidae family consists of 14 genuses, 26 species, and 18 sub-species, while Scorpionidae family has three genuses and four species. The lack of basic knowledge, including the geographical distribution, clinical manifestations, and specific treatments related to scorpiofauna justifies such multidisciplinary studies. The venom of two endemic Iranian scorpions, including Hemiscorpius lepturus (H. lepturus) and Odonthubuthus doriae (O.doriae) have considered as an effective source of new neurotoxin peptides for the further development of physio-pharmacological probes and designing the clinical trials. Such epidemiological information may improve the determinants of Iranian scorpion stings in order to plan and implement effective public health intervention.
Hemiscorpius lepturus scorpionism poses one of the most dangerous health problems in many parts of the world. The common therapy consists of using antivenom antibody fragments derived from a polyclonal immune response raised in horses. However, this immunotherapy creates serious side effects, including anaphylactic shock sometimes even leading to death. Thus, many efforts have been made to introduce new replacement therapeutics that cause less adverse reactions. One of the most attractive approaches to replacing the available therapy is offered by single-domain antibody fragments, or nanobodies (Nbs). We immunized dromedaries with H. lepturus toxin and identified a functional recombinant Nb (referred to as F7Nb) against heminecrolysin (HNc), the major known hemolytic and dermonecrotic fraction of H. lepturus venom. This Nb was retrieved from the immune library by phage display selection. The in vitro neutralization tests indicated that 17.5 nmol of the F7Nb can inhibit 45% of the hemolytic activity of 1 EC100 (7.5 μg/ml) of HNc. The in vivo neutralization tests demonstrated that F7Nb had good antihemolytic and antidermonecrotic effects against HNc in all tested mice. Surprisingly, F7Nb (8.75 nmol) neutralized 1 LD100 of HNc (10 μg) via an intracerebroventricular route or 1 LD100 (80 μg) via a subcutaneous route. All of the control mice died. Hence, this Nb is a potential leading novel candidate for treating H. lepturus scorpionism in the near future.-Yardehnavi, N., Behdani, M., Pooshang Bagheri, K., Mahmoodzadeh, A., Khanahmad, H., Shahbazzadeh, D., Habibi-Anbouhi, M., Hassanzadeh Ghassabeh, G., Muyldermans, S. A camelid antibody candidate for development of a therapeutic agent against Hemiscorpius lepturus envenomation.