Scorpion Envenomation

(1)

Scorpion

Envenomation

Scorpion envenomation is a common event in the

southwestern United States. Although most

scor-pion species are not dangerous to man, there exists

in the southwestern United States a potentially

lethal scorpion, Centruroides scuipturatus Ewing

(Fig 1), which produces a neurotoxic venom. We

report an eight-year experience with C scuipturatus

stings in Phoenix, Arizona, review the literature,

and discuss the pathophysiology of the symptom

complex. Suggestions are made for further research.

MATERIALS AND METHODS

A retrospective study was made of all cases of

scorpion envenomation seen from 1970 through

1978 in four large Phoenix hospitals: Maricopa

County General Hospital, Good Samaritan

Hospi-tal, Phoenix Indian Medical Center, and St Joseph’s

Hospital and Medical Center. The charts of 24

patients were reviewed for patient’s age, symptoms

on admission, initial diagnosis, physical findings,

treatment, hospital course, and complications.

RESULTS

Forty percent of patients were less than 4 years

of age and 80% less than 10 (Fig 2). Symptoms

observed in our series are listed in Fig 3. The most

common symptoms were local pain, restlessness,

and roving eye movements. The symptom complex

varied with the patient’s age. All patients more than

10 years of age complained of local pain, and none

experienced restlessness, whereas only 28% (4/14)

of patients less than 10 years of age complained of

local pain and 85% (12/14) experienced marked

agitation. Symptoms began within 60 minutes of the sting in all patients. Time of onset of symptoms

was unrelated to age or site of sting. Symptoms

persisted for three to 30 hours. All patients more

than 10 years ofage were symptom free by 10 hours.

In contrast, all patients less than 3 years of age

experienced symptoms for more than ten hours and,

in general, the duration of symptoms was inversely

related to the patient’s age.

Visual symptoms occurred in 12 patients,

consist-ing of roving eye movements (8), nystagmus (3),

and “oculogyric movements” (1).

Six

patients had

respiratory distress: four had inspiratory stridor and

Reprint requests to (M.E.R.) Department of Pediatrics,

Man-copa County General Hospital, 2601 E Roosevelt St, Phoenix,

AZ 85008.

American Academy of Pediatrics.

two had expiratory wheezing. All patients with

res-piratory distress were less than 6 years of age. Two required assisted ventilation. “Frothy sputum” was

noted in two patients. Excessive salivation was

noted in five. Three patients were initially

misdi-agnosed as foreign body aspiration, allergic

reac-tion, and asthma, respectively. One child underwent bronchoscopy, and two were treated with

epineph-rine and/or antihistamines with no improvement in

symptoms. Eight patients were hypertensive on

admission. Three had systolic hypertension only,

and

five had systolic and diastolic elevations.1 Seven

of the eight hypertensive patients were less than 7

years of age. One patient was believed to have had

seizures. This child had diffuse slowing in the left

temporal region on a subsequent EEG tracing.

Medications given to combat envenomation

symptoms in our series included antivenin, pheno-barbital, calcium gluconate, epinephrine, diazepam

(Valium), hydrocortisone, and diphenhydramine.

Three patients received no medications. There was

no correlation between variety, dose, or duration of

medication and length of symptoms.

Complications recorded in our series included respiratory arrest (2 patients) and prolonged

leth-argy (4 patients). All complications occurred in

patients less than 6 years of age. Both patients who

suffered respiratory arrest had received over 15 mgI

kg of phenobarbital in the first two hours of

hospi-talization.

DISCUSSION

Scorpion

The scorpion is an arthropod possessing a hard

exoskeleton, two powerful pinching claws

ante-riorly, and a “tail” (pseudoabdomen) which ends in

a bulbous enlargement, the telson. The latter

struc-ture bears coupled poison glands and tapers to a

stinger, which is thrust into the prey. Venom is

extruded through an orifice near the end of the

stinger. The scorpion grasps spiders and larger

in-sects upon which it feeds in its claws and stings

them to death by means of the pseudoabdomen

arching forward over its own head. The scorpion is

a nocturnal animal that hibernates in winter.

Dur-ing the day, it seeks shelter under stones or debris

but may crawl into a home or items of clothing.2

Although approximately 650 species of scorpions

exist, only a limited number are dangerous to man.

Arizona and parts of Texas, California, and

north-ern Mexico make up the habitat of the neurotoxic

C scuipturatus. It is small, slender, and yellowish in

color. Its size ranges from about 1.3 cm when it

leaves the mother’s back to about 7.6 cm when fully

(2)

I

H

‘H

2 3 4 5

<lyr. 1-4 5-10

1

Fig I. Centruroides scuipturatus Ewing.

No. of Patienfs

Age

Fig 2. Patients’ age.

base of the stinger allows differentiation from

non-neurotoxic scorpions indigenous to the Southwest.3

Scorpion Venom

Scorpion venoms are neurotoxic, thermostable,

low molecular weight basic proteins. They consist

of single polypeptide chains of approximately 65

amino acids cross-linked by four disulfide bridges.

Four potent and closely related neurotoxins have

been isolated from C scuipturatus and designated

toxins I to IV. The amino acid sequence of toxin I has been elucidated.4 The venom composition

var-ies not only with the species and the season, but

also with the age and nutritional state of the

scor-pion.5

The target structures of the scorpion venoms are

excitable membranes. When applied to desheathed

nerves of presynaptic terminals, they increase the

sodium permeability of the resting membrane.6 The

venom of C scuipturatus, in vitro, has a direct and

marked effect on the neuromuscular junction, a

lesser effect on single muscle fibers, and very little effect on conduction along myelinated nerves.7

Ap-Tachycarda 22

Pain at Site 1 1

Restlessness

-

9 Roving Eye Movements 8

Hypertension 8

Tachypnea 6

Respiratory Distress 6 Encess Salivation 5 Blurring of Vision 4

Slurred Speech 4 Stridor 4 Frothy Sputum 2 Poor Coordination 2

Paresthesias 2

Vomiting 2 Wheezing 2

Dysphagia

#{149}

1

6 Fig 3. Recorded signs and symptoms in 24 patients

with scorpion sting.

plication of venom directly to denervated skeletal

muscle preparations causes repetitive contracture

of the muscle. In vivo, the venom acts at the

pre-synaptic terminal of the neuromuscular junction

causing depolarization. Depolarization causes in-creased calcium permeability at the presynaptic

terminal, provoking entry of calcium ion and release

of acetylcholine.8 This, in turn, results in muscle

twitching and fibrillations. The excitatory effects of

scorpion venom can be blocked by strychnine, a

known blocking agent of the neuromuscular

june-tion at the presynaptic terminal. Venoms from var-ious scorpions have also been shown to release

acetyicholine from postganglionic parasympathetic nerves.9

The scorpion venom

also affects

the sympathetic

nervous system. Venom from a South American

scorpion, Tityus serrulatus, exerts a

sympathomi-metic effect on isolated guinea pig heart. Intrave-nous administration of scorpion venom causes im-mediate and sustained hypertension in rats and a

striking increase in serum catecholamines. The

scorpion toxin of Leiurus quinquestriatus has been shown to induce the prolonged release of

catechol-amines by a direct action on the membrane of

adrenergic neurons.9 Sympathetic activity may

ac-count for the majority of symptoms seen clinically. Pure scorpion neurotoxins are also strongly car-diotoxic. One neurotoxin causes embryonic heart

cells in culture to increase cell beat frequency. It decreases the amplitude of contraction at low con-centrations and causes fibrifiation at higher

concen-trations.8 Stings by the Buthus quinquestriatus

species found in India cause heart failure,

pulmo-nary edema, electrocardiographic changes of “early

myocardial infarction-like patterns,” and elevated

(3)

hy-potension and often bradycardia. This clinical pie-ture has been attributed to catecholamine-induced

hypoxia. Adrenergic blockers reduce the severity of

the clinical picture. Twenty-four hour catechola-mine secretion was markedly increased in the first day after a sting in two patients studied.

Further-more, a synergistic effect of epinephrine on scorpion

venom has been reported. Pathologic changes in

the myocardium of fatal cases have included inter-stitial edema and muscle fiber necrosis; however,

some cases have no morphologic changes.5”#{176} Death

appears to be due to pulmonary edema and penph-eral circulatory failure.11

Signs and Symptoms

The symptom complex caused by C scuipturatus,

according to previous reports, begins with an

ab-rupt, painful tingling or burning sensation at the

site of the sting.3 In our series, however, only 50%

of patients reported local pain. All patients more

than 10 years of age complained of pain, but only

28% of the younger patients did so. The site of the

sting is said to be hyperesthetic with pain to the

touch extending proximally along an extremity for

as long as ten days.3 In our series, as in previous

reports, the site of the sting was never identified.

The presence of swelling, ecchymosis, or erythema

at the site indicates the offending scorpion was not

a neurotoxic variety.’2

Other symptoms recorded in the literature are

pharyngeal spasms, extreme restlessness (especially

in children), convulsions, drooling, wheezing,

blind-ness or inability to focus eyes, incontinence of urine

and feces, hyperthermia, cyanosis, and gastric

dis-tention.3 Previously unreported symptoms present

in our series include poor coordination, dysphagia,

vomiting, and “roving eye movements.”

Special clinical difficulty is encountered with

re-gard to respiratory symptoms and convulsions.

Mis-diagnoses in

this

series were all due to wheezing, respiratory distress, and/or stridor. Although

res-piratory effects may be considerable, other

symp-toms are present which should reveal the true

di-agnosis, especially agitation out ofproportion to the

respiratory findings. Convulsions may be difficult

to differentiate from the extreme hyperactivity.

Electroencephalographic recording in the acute

stage is impossible because of continuous body

movement.

This study also indicates that the nature and

duration of symptoms are remarkably influenced

by age. All patients more than 10 years of age were

symptom free by ten hours, whereas symptoms

persisted in younger patients for as long as 30 hours.

Pain at the site of the sting was a predominant

symptom in the patient more than 10 years of age;

however, restlessness was the most common

pre-senting symptom in the younger patient.

Diagnosis

In children, the diagnosis of scorpion sting due to

the neurotoxic species presents unique problems to the physician. Since the site cannot be identified

and children may not communicate accurately the

history of a sting, diagnosis is usually made by clinical presentation alone. In the young child,

per-petual restlessness characterized by writhing,

jerk-ing, and flailing is extraordinary and is duplicated

by little else in medicine. Such extreme agitation

may also be seen with convulsions, corneal abrasion,

intra-abdominal catastrophe, and phenothiazine

in-toxication. History, physical examination, and nat-ural course will usually exclude other conditions.

Treatment

Cryotherapy, antivenins, sedatives,

anticonvul-sants, calcium, corticoids, adrenocorticotropic

hor-mone, and antihistamines have been used for the treatment of C scuipturatus stings.’2 Immediate

application of ice to the area of the sting has been

recommended to reduce pain.’3 The application of a cube of ice for a few minutes may provide some relief and is harmless. There is no evidence,

how-ever, that more extensive cryotherapy is helpful.

An antivenin produced from cat serum has been

distributed in Arizona in the past.’2 The Maricopa

County Medical Society Board of Directors

re-viewed the product and “determined the available

evidence failed to allow the Society’s endorsement.”

Its investigation also failed to show appreciable

usage by hospitals and physicians in Arizona!4 An

antivenin produced from goat serum is now

avail-able in Arizona.

Phenobarbital is perhaps the most commonly

used chemotherapeutic agent in scorpion

enven-omation. Massive doses have been recommended by Stahnke.3 Twelve patients (54%) in our series

received phenobarbital; in eight cases 15 mg/kg or

more was given. The two children who required assisted ventilation had both received 15 mg/kg of

phenobarbital in the first two hours of treatment.

Unfortunately, the literature suggests that such

high doses will be well tolerated. In fact, it has been

recommended that adults receive 1,300 mg of

phe-nobarbital and that infants receive at least

260

mg.3

It appears that complications that occurred in our

series were related to the use of high-dose

(4)

symp-toms. Certainly the extreme agitation seen in young

children can be controlled with enormous doses of

barbiturates; however, in the authors’ opinion,

this

therapeutic regimen cannot be recommended, and

we suggest that sedatives be used cautiously. The

dangers of excessive doses should be realized and the temptation to totally control the restlessness be resisted. All infants should be observed closely in

an intensive care setting.

Mortality

At one time C scuipturatus caused more deaths than any other venomous animal in Arizona. In

spite of greatly increased population in the state, the number of deaths diminished more than three-fold between 1930 and 1970. The cause of such a

dramatic decrease has been attributed to eradica-tion techniques as well as to improved

therapeu-tics.2 There have been no reported deaths in

Ari-zona since 1970 (5. Friedman, personal

communi-cation, 1979). With improved transportation and

clinical care, minimal mortality should result except

in exceptional circumstances.

Needs for Future Research

Implicated in the pathogenesis of the extreme

restlessness seen in C sculptur#{224}tus stings is a virtual

“sympathetic storm” with release oflarge quantities

of sympathetic neurotransmitters. Research is

needed on the efficacy of sympathetic blocking

agents in this condition. In theory, therapy could

then be specific rather than symptomatic. Also

vitally

needed are objective controlled evaluations

of the drug regimens currently in use. Finally, data

are needed on the incidence (if any) and nature of

seizure activity in order to ascertain the need for anticonvulsant therapy versus simple sedation.

On the basis of the foregoing information, we

recommend that all children who have been stung

by a Centruroides scuipturatus and develop

sig-nificant symptoms should be admitted to a pediatric

intensive care unit where neurologic,

cardiovascu-lar, and respiratory status can be monitored closely.

We cannot recommend the use of goat serum

anti-venin since

this

product has not been, in our

opin-ion, adequately investigated. If barbiturates are

used, they should be given cautiously and only in

anticonvulsant doses. We are currently studying a

management regimen of Centruroides

envenoma-tion which excludes chemotherapy. In the past,

fatalities in young children were likely secondary to cardiac complications: hypertension, arrhytKmias,

and heart failure. In light of our current knowledge

of the scorpion neurotoxins, the use of propranolol

or other sympatholytic agents might be warranted

in a young child with severe hypertension and/or

congestive heart failure. Further work in

this

area, however, is needed.

SUMMARY

A potentially lethal neurotoxin-producing

scor-pion, Centruroides scuipturatus, exists in the

southwestern United States. The most common

symptoms of envenomation of 24 patients included

local pain, restlessness, and roving eye movements.

In

this

series 80% of cases were in children less than

10 years of age. Pain at the site of the sting was a

predominant symptom in the patient more than 10

years of age; however, extreme and perpetual

rest-lessness was the most common symptom in the

younger patient. The diagnosis in children is usually

made by clinical presentation alone since the site of the sting cannot be identified and children may not

communicate the history of the sting. The most

commonly used chemotherapeutic agent is

pheno-barbital. There is no evidence, however, that this

drug

decreases morbidity or mortality, and massive

doses of phenobarbital were associated with two

respiratory arrests in

this

series. The nature of

scorpions and their venoms is discussed. Research

is needed regarding the use of sympathetic blocking

agents in scorpion envenomation.

ACKNOWLEDGMENT

The authors thank Ms Barbara Bengtson for expert secretarial assistance.

REFERENCES

MARY ELLEN RIMSZA, MD

Maricopa County General Hospital

DALE R. ZIMMERMAN, DO

PAUL S. BERGESON, MD Good Samaritan Hospital

Phoenix, Arizona

1. Haggerty RJ, Maroney MW, Nadas AS: Essential hyperten-sion in infancy and childhood. Am J Dis Child 92:535, 1956 2. Stahnke HL: Scorpiology. Turtox News 45:218, 1967 3. Stahnke HL: Arizona’s lethal scorpion. Ariz Med 29:490,

1972

4. Babin DR, Watt DD, Goes SM, et al: Amino acid sequence of neurotoxin I from Centruroides scuipturatus Ewing. Arch

Biochem Biophys 166:125, 1975

5. Yarom R: Scorpion venom: A tutorial review of its effects in men and experimental animals. Clin Toxicol 3:561, 1970 6. Chahl LA, Kirk EJ: Toxins which produce pain. Pain 1:3,

1975

7. Russell FE: Pharmacology of animal venoms. Clin Phar-macol Ther 8:849, 1967

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neu-scorpion sting. A clinical and electrocardiographic study of 50 cases. Indian Heart J 28:88, 1975

12. Stahnke HL, Stahnke J: The treatment of scorpion sting.

Ariz Med 14:576, 1957

13. Stahnke HL: Hypothermia and scorpion venomation.

South-western Med 46:286, 1965

14. Arizona Medical Association Notes. Section on Poison Con-trol. Ariz Med 29:797, 1972

rotoxins. Mode of action on neuromuscular junctions and synaptosomes. Biochim Biophys Acta 448:607, 1976

9. Moss J, Thoa NB, Kopin IJ: On the mechanism of scorpion toxin-induced release of norepinephrine from peripheral ad-renergic neurons. J Pharmacol Exp Ther 190:39, 1974 10. Geuron M, Weizman S: Catecholamines and myocardial

damage in scorpion sting. Am Heart J 75:715, 1968 11. Kothari UR, Shah SS, Doshi HV, et al: Myocarditis from

Mouthwash:

A Source

of

Acute

Ethanol

Intoxication

Poisoning is an important cause of accidental

death in children under the age of 5 ars2 The

most frequently ingested poisons are those that are

commonly available to families, are kept in easily

accessible places in the and are not

pack-aged in child-resistant containers.4 Mouthwashes

are easily accessible, high-ethanol products mar-keted without child-resistant packaging. They are

used daily by millions of people in spite of the fact

that their efficacy remains unproven.7 As the

Na-tional Academy of Sciences concluded, “There is no

convincing evidence that any medicated

mouth-wash, used as a part of a daily hygiene regimen, has

therapeutic advantage over a physiologic saline

so-lution or even water.”8

We recently treated a child with severe ethanol

intoxication resulting from the ingestion of

mouth-wash. Case reports of accidental pediatric ethanol

intoxication have appeared sporadically, focusing

on secondary hypoglycemia’3 or on other unusual

medical pets” We have found only one report

of mouthwash-related intoxication.’3 The blood

ethanol levels in both children in that report were only minimally elevated and the report dealt

pri-manly with hypoglycemia. Our patient had a

dan-gerously high ethanol level.

CASE REPORT

The parents of a previously healthy 33-month-old girl

found her stuporous outside an upstairs bathroom at

11:00 AM. A partially empty 16-oz bottle of “generic”

mouthwash containing 18.5% (v/v) ethanol was found

nearby. An ambulance arrived within ten minutes. An

intravenous infusion of 5% dextrose in hypotomc saline

was begun, and the child was transported to the

emer-gency room.

Reprint requests to (W.G.T.) New Mexico Poison, Drug Infor-mation and Medical Crisis Center, University of New Mexico, Albuquerque, NM 87131.

American Academy of Pediatrics.

The approximate time of ingestion was 9:00 AM. Based

on the parents’ estimate of bottle contents prior to inges-tion and the amount of mouthwash remaining in the bottle, we estimated that 11 oz of mouthwash (48.2 gm of absolute ethanol) were unaccounted for and were presuin-ably ingested.

On admission, this normally developed child smelled

strongly of mouthwash. Her weight was 13.1 kg. Rectal

temperature was 35.4 C (95.7 F); pulse rate 125 beats per

minute; respiratory rate 28/mm; and blood pressure 88/ 50 mm Hg. She was comatose and responded only to deep

pain. Her pupils were midpoint and reactive and the fundi were normal. The gag reflex was present, the deep tendon reflexes were difficult to elicit but symmetrical, and the

toes were down-going.

Initial laboratory data included the following: sodium

139 mEq/liter; potassium 3.6 mEq/liter; chloride 106

mEq/liter; HCO3 9 mEq/liter, BUN 24 mg/100 ml; and glucose 97 mg/100 ml. Arterial blood gases were as fol-lows: pH 7.18; Pco2 25 mm Hg; Po2 102 mm Hg; and

HCO3 9 mEq/liter. Blood alcohol level was 306 mg/100

ml approximately 3/2 hours after ingestion.

Treatment consisted of nasogastric lavage with normal

saline, warming by radiant heater, and administration of

intravenous fluids, and supplemental bicarbonate. Within

four hours, the child’s rectal temperature was normal. Eight hours after the ingestion the blood alcohol level

was 128 mg/i#{174} ml. By 18 hours after admission, the

child was responding appropriately and had normal blood

gases and electrolytes. She was discharged home on the

second hospital day. A public health nursing referral was

made for a follow-up home visit.

DISCUSSION

During an 18-month period (January 1978 to

June 1979), reports of 422 cases of mouthwash

ingestion in children under the age of 6 years were

collected by the National Poison Center Network

from its member poison centers in selected areas of

the United States (unpublished data, 1979). Total

reported poisonings in

this

age group were 128,370. As with most accidental ingestions, 2 and 3 year

olds were the most common victims of acute

mouth-wash poisoning, accounting for 145 (34.3%) and 132

(31.3%) cases, respectively. Of these patients, 56

(13.3%) were symptomatic, 26 (6.2%) were treated

in an emergency room, and 8 (1.9%) required

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1980;66;298

Pediatrics

Mary Ellen Rimsza, Dale R. Zimmerman and Paul S. Bergeson