Management of Acute Poisoning With Activated Charcoal

(1)

324 PEDIATRICS

Vol. 54

No. 3 September 1974

pared to meet minds that, from immaturity,

apa-thy, or a feeling of nonrelevance, may be

unrecep-tive. Active poison prevention programs based on

the educational approach have been effective in

well child clinics, preschool nurseries, and

ele-mentary schools. When the enthusiasm of the

edu-cator is high it is more likely to be transmitted to

the recipient-be it a physician relating the need

for syrup of ipecac and poison prevention

precau-tions to a mother of an active inquisitive infant or

a visitor to a kindergarten class from a poison

in-formation center in the community who helps an

eager young child recognize Mr. “Yuk” as a

“friendly” danger sign.

The illusive key to the problem of accidental

childhood poisoning is prevention. Until it is found

by some future Utopian society, our failures will

continue to come to us for care. These papers

should help us render better service to our

chil-dren.

ROBERT G. SCHERZ, M.D.

Guest Editor

Management

of Acute

Poisoning

With

Activated

Charcoal

LTC Donald G. Corby, MC, and LTC Walter J. Decker, MSC

1r(;uz the (:!i,iic’al Research Sc’rtice, htz.si;nons Arnzy Medical Center, I)enuer, and the I S tony Area Medical

IAII)oratori/. fort Saii Ilmiston, Texas

Many toxicologists now consider administration

of activated charcoal as the most effective means

of reducing the systemic absorption of many

poi-sons13; nevertheless, many pediatricians and emergency room physicians ignore this valuable

treatment. The adsorbent properties of charcoal

have been known for almost two centuries.

Nu-merous articles have appeared in the European

literature0 extolling its virtues as an adsorbent and

antidote. However, it has been only during the

past decade that toxicologists have begun to

quan-titatively evaluate the ability of this substance to

adsorb drugs in vitro or to reduce absorption of

toxins from the gastrointestinal tract. In this

re-view, we shall discuss some of these studies and

at-#{176}Thereader is referred to the excellent review, “The Black Bottle” by Holt and Holz (I. Pediat., 63:306, 1963) for a

summary of this early literature and complete listing of

ref-erences.

tempt to provide the reader with practical

infor-mation and recommendations on use of this agent

in emergency management of acute childhood

in-gestions.

ANTIDOTAL EFFICACY-RECENT

EXPERIMENTAL

EVIDENCE

In 1968 we conducted a series of studies to

de-termine the ability of activated charcoal to adsorb

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

ADDRESS FOR REPRINTS FOR ALL ARTICLES IN THIS SECTION: Robert C. Scherz, M.D., Medical Director,

Mary Bridge Children’s Health Center, Tacoma,

Washing-ton 98405.

at Viet Nam:AAP Sponsored on September 8, 2020 www.aappublications.org/news

(2)

I

TABLE I

Dnu; ADSORPTION l %‘ITIW ACTIVATEI) CHARCOAL#{176}

Drug

\‘o of

10 Tablets

20

Acetylsalicylic acicj-325 mg Amphetamine-5 mg Chlorpheniramine-4 mg Colchicine-O.5 mg 90 94 96 94 85 92 96 92

Diphenylhydantoin-100 mg 90 86

Ergotamine-1 mg 92 90

Phenobarbital-32 mg 86 45

Primaquine-25 mg Propoxyphene-32 mg Digitoxin-100 mg 97 100 66 94 85 60 Probenicid-100 mg Quinacrine-325 mg Acetaminophen-325 mg 58 68 23 40 26 8

Glutethimide-500 mg 45

-Meprobamate-400 mg Propylthiouracil-50 mg 25 33 -23

Quinidine-325 mg 44 1

Quinine-325 mg 32 1

Phenylbutazone-100 mg 15

-Ferrous sulfate-325 mg 5 1

Chloroquine-500 mg 6

-0Values expressed as % dnig adsorbed after 20

mm-utes.

in citro a number of commonly prescribed dnigs

found in the home (Table I). Although these data

should not be construed as primafacie

evidence

of

clinical antidotal efficacy, two facts are apparent:

(1)

the adsorptive action of active charcoal varies

considerably, and (2) the adsorptive affinity for

certain agents, e.g., aspirin, suggests that its use as an antidote is feasible.

Table II lists therapeutic agents for which

anti-dotal in civo effectiveness has been demonstrated.

Activated charcoal has been shown to reduce

ab-sorption of salicylate from the gastrointestinal tracts of rats, dogs,6 and man.7’8 In a recent study,7

administration of activated charcoal to human

adult volunteers 30 minutes after ingestion of

aspi-rin resulted in 50% reduction of serum salicylate

concentration. The simultaneous administration

of apomorphine (0.03 mg/lb of body weight)

en-hanced this effect, thereby reinforcing our

orig-ma! conviction that a combined regimen of

macti-vation and emesis is more efficient than either

method alone (Fig. 1). In a related study Levy and

Tsuchiya8 determined the urinary excretion of

salicylate and metabolites in human adults treated

experimentally with charcoal with similar results.

Activated charcoal has also been shown to

re-duce absorption of other analgesics and

antipyret-ics. Levy and Gwilt9 showed that acetaminophen

absorption could be reduced by charcoal (77% and

69%)

in the two human subjects studied;

compa-rable inhibition

of paracetamol

adsorption

was

re-ported by Dordoni et The charcoal absorption

of salicylamidehl

and mefanamic

acid’2

in

experi-mental animals suggests that this agent might also

be efficacious

for treatment

of ingestions

of these

compounds.

Charcoal avidly binds propoxyphene

hydro-chloride

in vla

Chemish

et 14

demonstrated

significant reductions in serum propoxyphene

1ev-els

in human subjects experimentally treated with

repeated doses of activated charcoal (Fig. 2).

These

data and reports

of prevention

of toxicity

in

experimental

animals13

and

man’6

indicate

that

activated charcoal may be effective in treatment

of propoxyphene

overdose.

Although no human data are available, results

with experimental animal studies have led to

rec-ommendations for use of charcoal as an antidote

for two other groups of therapeutic agents:

seth-tive hypnotics’7 and tricyclic antidepressants.

Fiser et al.21

showed

that

administration

in

mon-grel dogs of activated charcoal 30 minutes after

phenobarbital or glutethimide ingestion reduced

TABLE II

ANTIDOTAL EFFECTIVENESS OF ACTIvATED CHARCOAL-1X

VIV() EvInENcE

Experimental

Animals Man References

ANALGESICS AND ANTIPYRETICS

Acetylsalicylic acid x x 7,8,25,30

Sodium Salicylate x 5

Salicylamide x 11

d-Propoxyphene

hydrochloride (Darvon) x x 14,15,16

Paracetamol (Trigesic) x 10

Acetaminophen (Tylenol) x 9

Mefanamic acid (Ponstel) x 12

BARBITURATES-SEDATIVES-HYPNOTICS

Barbital x 30

Phenobarbital x 21,23,25,30

Pentobarbital x 25,30

Secobarbital (Seconal) x 21

Glutethimide (Doriden) x 21,30 Ethchlorvynol

(Placidyl) x 21

TRANQUILIZERS-ANTIDEPRESSANTS Chiorpromazine

(Thorazine) x 30

Imipramine (Tofranil) x 19,20

Nortriptyline (Aventyl) x 18

MISCELLANEOUS

Chloroquine (Aralen) x 23,30

Isoniazid x 27

Chlorpheniramine x 25,30

Phenylpropanolamine x 30

Propantheline x 31

PEDIATRICS FOR THE CLINICIAN

325

(3)

ASPIRIN

A

-I

0

‘U A.

4

C, 20

10

5

2

1

I

10

5 SE

-Wa’,

0 0

‘U A.

4

CD

0

U

0 4 8 12 24

50 PROPOXYPHENE

a

p

HOURS

SINCE

INGESTION

1’u;. 1.Seinilogarithmic plot of serum salicvlate

coiicentra-tiOUS ill ten nornal adult volunteers after oral administration

of ten 0.3-gui aspirin tal)lets, replotteci from l)ecker et al. A.

control subjects: B, activated charcoal (3() gui ) adninistered 3() minutes after aspirin; C, activated charcoal +

apomor-phine (0.03 mg ler B) at 30 minutes after aspirin.

serum levels by 50% of control values: 56% to 74%

drug reduction, respectively (Fig. 3).

Rauws and van Noordwijko recently evaluated

the ability of activated charcoal to interrupt

en-terohepatic recycling of tricyclic antidepressants. In this study it was shown that pretreatment with

activated charcoal significantly reduced levels of

imipramine and its metabolite, desipramine,

found in heart, lung, and liver of rats. Alvan#{176}also demonstrated that in humans activated charcoal

reduces absorption of nortriptyline from the

gas-trointestinal tract.

Although these studies clearly demonstrate that activated charcoal is a highly effective antidote

for a broad spectrum of commonly ingested drugs,

it should be emphasized that its adsorptive

capac-ity in rit:o for many toxic agents is unknown.

Therefore, indiscriminate use of activated

char-coal should be discouraged and its selection as an

antidote should be based on rational evidence

ob-tamed experimentally, preferably from

quantita-tive in rico investigations.

STABILITY OF CHARCOAL-DRUG COMPLEX

Originally it was felt that the charcoal-drug

HOURS

SINCE

INGESTION

Fic .2. Semilogarithmic plot of serum propoxyphene

concen-trations in six normal adult volunteers after oral administra-tion of propoxyphene hydrochloride ( 130 mg), replotted

from Chernish et al. A, control subjects B, activated char-coal (0.8 gui) administered start and every ten minutes for

four doses.

complex was stable; recent studies,ui however, in-dicate that the competitive effects of other con-stituents of gastrointestinal fluids and associated higher pH may cause minimal degrees of desorp-tion to occur during passage through the

gastroin-testinal tract. However, from a practical

stand-point, this effect is inconsequential since it is

markedly diminished with increasing doses of

charcoal.

EFFECT OF DELAY IN ADMINISTRATION

Effectiveness of this antidote is determined by

several factors.

Time Interval Between Ingestion and Treatment

In general, charcoal should be administered

within 30 minutes of ingestion to achieve

signifi-cant inhibition of drug absorption. However, Levy

and Tsuchiya have shown that the charcoal can

“catch up” and bind poisons which have already

passed through the pylorus5; as such,

administra-tion should not be withheld where large amounts

of toxic substances have been ingested.

Rate of Absorption of the Drug

Charcoal is less effective in treatment of

com-pounds which are rapidly absorbed from the

gas-trointestinal tract. For example, charcoal

(4)

HOUIS SINCE INGESTION

A a

0 0

a

4

0

a

Fi;. :3. Seinilogarithiuic plots of seruii phenobarbital +

gIll-tethimide concentrations in five dogs after oral administra-tion of Phcnol)arl)ital (72 ng/kg) or glutethiinide (3 gin ), re-1)l0tte(l from liser (‘t (1!. ‘A, control dogs; B. activated

char-coal (2() gin ) a(lluinistere(l 30 minutes after drug.

tively reduced senim secobarbital concentrations in dogs when administered 30 minutes after the drug; however, no appreciable reduction in serum levels was observed when charcoal administration was delayed for one 1121 Conversely, repeated

doses of activated charcoal further reduced

ab-sorption of slowly absorbed drug and those which

undergo an enterohepatic recycling such as glu-tethimide, digitoxin, and the tricyclic

antidepres-sants.

Gastric Motility

Mans’ intoxications, such as aspirin, sedatives and hypnotics, are characterized by prolonged

re-tention of the ingested drug in the stomach. In these instances, increased absorption can result if

large doses of activated charcoal are

adniinis-tered.

SELECTION OF ANTIDOTE

Charcoals vary greatly in their adsorptive

ca-pacity; some charcoals are designedfor the

pur-pose of selective adsorption, while those used as

antidotes require a broad spectrum of adsorption. Small particle size, low mineral (ash) content, and

a large total surface area are the characteristics of

better adsorptive capacity. Charcoals derived

from vegetable sources, i.e., wood pulp, best fit these requirements.

There are numerous charcoal preparations;

however, only four have been recommended as antidotes: Norit A (American Norit Co.), Activat-ed Charcoal-Merck (Merck and Co.), Nuchar C (\Vest Virginia Pulp and Paper Co.), and Darco

G60 (Atlas Chemicals, I.C.I. America). Darco G60 prol)ably should not be used clinically since it does

not meet current United States Pharmacopeia

specifications for residue after ignition.22

Activated charcoal is most effective when

administered as a “slurry”: activated charcoal

powder mixed with tap water. The so-called

uni-versa! antidote, a combination of two parts

acti-vated charcoal, one part magnesium oxide, and

one part tannic acid has been shown to be less

ef-fective in activated charcoal powder.2 Because of

longer disintegration times, commercial charcoal

tablets and granules have also been shown to be

less effective.24

Reluctance by pediatricians and emergency

room physicians to use activated charcoal has stimulated interest among toxicologists to

evalu-ate other “more esthetic” adsorbents. The

effica-cy of Arizona Montmorillonite, evaporated milk

and attapulgite (Pharmasorb-regular, Engelhard

Mineral and Chemical Co.) have been studied. 226

These substances possess adsorptive capabilities; however, in experimental animals, none were

found as effective as powdered charcoal.

DOSAGE OF ANTIDOTE

Available quantitative in cito evidence727

in-dicates that a charcoal to poison ratio of at least

8: 1 is required for consistent effective reduction of poison absorption. Food in the stomach further

re-duces adsorption by charcoal. Therefore, since

ac-tivated charcoal is innocuous, the only limiting

factor in administration is the quantity the

recipi-ent is willing to accept. Accordingly, the optimal dose of antidote is the maximum amount that can

be given practically.

ACCEPTANCE

The major objection of physicians to the use of

activated charcoal is its disagreeable physical

characteristics. Arena25 said:

“To get a 2 year old to swallOw powdered

char-coal is a rare accomplishment indeed. The

drawback to this compound is that it is black

and many children will refuse to drink it and if

spewed, it spots uniforms, clothes, walls, and

personnel.”

Iii 1970, this widely held assumption was

test-ed.2u1 Fifty ‘oung children (ages 18 months to 5

years) appearing in the emergency room of Wi!-liani Beaumont Army Medical Center for

treat-irient of acute ingestion of drugs and toxic

house-hold products were studied. Forty-three (86%)

readily accepted the activated charcoal, and 38

(76%) consumed from 95% to 100% of the dose

administered. These results suggest that adversion to activated charcoal rests primarily, not with the

child, but with the clinician, nurse, or ancillary

emergency room personnel. They further indicate

that an expectant, firm, positice approach will

re-stilt in successful administration to most children.

327

(5)

A

However, greater acceptability might be

achieved by administering the charcoal slurry in

opaque, closed containers or by increasing

palata-bility. Preliminary studies in our laboratory

suggest that the addition of a flavoring agent to the

charcoal slurry does not significantly alter the in

titro

adsorptive

capacity

for aspirin.

SUMMARY

Activated charcoal has been shown to be an

ef-fective complexing agent for many drugs. The

quantitative in vivo evidence accumulated thus

far indicates that this agent can be a very valuable

adjunct in the initial phases of treating acute

in-gestions not only in the emergency room but also

as a first aid measure in the home. It is well

tolerat-ed in extremely high single doses, and there is no

known contraindication to its use in treatment of

acute drug ingestion. It is immediately effective

upon ingestion and can be given safely by

nonpro-fessionals; hence, its inclusion in household

first-aid supplies

is warranted.

In the emergency room,

activated charcoal can be administered by lavage

tube to an unconscious patient in large and

re-peated

doses and

can be continued throughout the acute phase of the clinical illness. The

effective-ness of activated charcoal can be enhanced by

em-esis induced by apomorphine before or after

char-coal administration. Since charcoal effectively

adsorbs ipecac, syrup of ipecac should be given

before the activated charcoal. Although it is not

uniformly efficacious for all drugs, activated

char-coal appears to be a generally useful adjunct for

gastrointestinal decontamination.

REFERENCES

1. HoD, L. E., Jr., and Holz, P. H.: The black bottle. J.

Pe-diat., 63:306, 1963.

2. Picchioni, A. L.: Activated charcoal-a neglected anti-dote. Pediat. Clin. N. Amer., 117:535, 1970.

3. Corby, D. (;., Fiser, R. C., and Decker, W. J.:

Reevalua-tion of the use of activated charcoal in the

treat-ment of acute poisoning. Pediat. Clin. N. Amer.,

17:545, 1970.

4. Decker, W. J., Combs, H. F., and Corby, D. C.: Adsorp-tion of dnigs and poisons by activated charcoal. Toxic. Appl. Pharm., 13:454, 1968.

5. Decker, W. J., Corby, D. G., and Ibanez, J. D., Jr.: Aspi-rin adsorption with activated charcoal. Lancet, 1:754, 1968.

6. Phansalkar, S. F., and Holt, L. E., Jr.: Observations on the immediate treatment of poisoning. J. Pediat., 72:685, 1968.

7. Decker, W. J., Shpall, R. A., Corby, D. C., Combs, H. F.,

and Payne, C. E.: Inhibition of aspirin absorption by activated charcoal and apomorphine. Clin. Pharm. Ther., 10:710, 1969.

8. Levy, C., and Tsuchiya, T.: Effect of activated charcoal on aspirin absorption in man, Part I. Clin. Pharm. Ther., 13:317, 1972.

9. Levy, C., and Gwilt, P. R.: Activated charcoal for acute

328 MANAGEMENT

OF POISONING

acetaminophen intoxication. JAMA, 219:621, 1972. 10. Dordoni, B., Willson, R. A., Thompson, R. P. H., and

Williams, R. : Reduction of absorption of paraceta-mol by activated charcoal and cholestyramine: A possible therapeutic measure. Brit. Med. J., 3:86,

1973.

11. Tsuchiya, T., and Levy, C.: Relationship between effect

of activated charcoal on drug absorption in man and its drug adsorption characteristics in vitro. J. Pharm. Sci., 61:586, 1972.

12. Glazko, A. J.: In Pharmacology of the Fenamates: III. Metabolic disposition. Ann. Phys. Med., 9 (Suppl.):

24, 1967.

13. Corby, D. G., and Decker, W. J.: Antidote for propoxy-phene. JAMA, 203:1074, 1968.

14. Chernish, S. M., Wolen, R. L., and Rodda, B. E.: Absorp-tion of propoxyphene hydrochloride by activated charcoal. Clin. Toxic., 5:317, 1972.

15. Corby, D. C., and Decker, W. J.:Treatment of propoxy-phene poisoning. JAMA, 205:25(), 1968. 16. LaCasse, Y. : personal communication.

17. Decker, W. J., and Corby, D. C.: Activated charcoal as a gastrointestinal decontaminant : Experiences with experimental animals and human subjects.

Clin. Toxic., 3:1, 1970.

18. Alvan, G.: Effect of activated charcoal on plasma levels of Nortriptyline after single doses in man. Europ. J. Clin. Pharm., 5:236, 1973.

19. Rauws, A., and van Noordwijk, J.: Activated charcoal in

tricyclic drug overdoses. Brit. Med. J., 4:298, 1972.

20. Crammer, J., and Davies, J.: Activated charcoal in tricy-clic drug overdoses. Brit. Med. J., 3:527, 1972. 21. Fiser, R. H., Maetz, H. M., Treuting, J. J., and Decker,

W.

J.:

Activated charcoal in barbiturate and gIn-tethimide poisoning of the dog. J. Pediat., 78:1045,

1971.

22. Activated carbon chaser chases poisons. Chemmunique, 22 (1973) IC.!. America.

23. Picchioni, A. L., Chin, L., Verhulst, H. L., and Dieterle, B.: Activated charcoal vs “universal antidote” as an antidote for poisons. Toxic. Appi. Pharm., 8:447,

1966.

24. Tsuchiya T., and Levy, C.: Dnig adsorption efficacy of commerdal activated charcoal tablets in vitro and in man. J. Pharm. Sci., 61:624, 1972.

25. Chin, L., Picchioni, A. L., and Duplisse, B. R.: Compara-tive antidotal effectiveness of activated charcoal, Arizona montmorillonite, and evaporated milk. J. Pharm. Sci., 58:1353, 1969.

26. Atkinson, J.P., and Azarnoff, D. L.: Comparison of char-coal and attapulgite as gastrointestinal seques-trants in acute dnig ingestions. Clin. Toxic., 4:31,

1968.

27. Chin, L., Picchioni, A. L., Bourn, W. NI., and Laird,

H. E.: Optimal antidotal dose of activated

char-coal. Toxic. AppI. Pharm., 26: 103, 1973.

28. Arena, J. M.: Aspirin poisoning-Gastric lavage, ipecac, or activated charcoal? JAMA, 212:327, 1970. 29. Calvert, W. E., Corby, D. C., Hebertson, L. M., and

Decker, W. J.:Orally administered activated char-coal: Acceptance by children. JAMA, 215:641,

1971.

30. Chin, L., Picchioni, A. L., and Duplisse, B. R.: The

ac-tion of activated charcoal on poisons in the diges-tive tract. Toxic. Appl. Pharm., 16:786, 1970.

31. Chaput de Saintoinge, D. M., and Herxheimer, A.: Acti-vated charcoal impairs propantheline absorption. Europ. J. Clin. Pharm., 4:52, 1971.

(6)

329

ACKNOWLEDGMENT

\,e wish to acknowledge the secretarial assistance

pro-vided by Ms. Val McCrill in the preparation of this

manu-script.

Narcotic

Poisoning

of Children

(1) Through

Accidental

Ingestion

of Methadone

and (2)

in utero

Saul Blatman, M.D.

lroiii f/U’ I)cpartmeut of \latcrnal and Child IIC(1!th, Dartmotiih .le(lical School, Ilam)ter, .Vc,t Jlantpshire

Narcotics have been known to man since pre-historic times, and they continue to be among the

most used analgesics in the practice of medicine. They comprise a group of drugs whose analgesic effect is coupled with euphoria and somnolence.

In addition, their spasmogenic effect on smooth

muscle has made them useful agents in the

allevia-tion of certain gastrointestinal tract symptoms.

For most narcotics, therapeutic dosage does not

produce serious untoward effects. Unfortunately,

they have a depressant effect on respiration by di-rectly influencing the respiratory center of the brain. This may be life threatening when recom-mended dosages are exceeded.

Narcotics have been abused since the

recogni-tion that they can induce euphoria and a feeling of

well being. Tolerance and physical and

psycho-logical dependence result from their repeated use.

The occurrence of withdrawal symptomatology in

humans using these drugs repeatedly helps to pro-duce a pattern of drug dependence; an individual has but to repeat a dose of drug in order to prevent

withdrawal symptoms. Abuse liability is thus

great.

All narcotics share this addiction potential.

Those most frequently prescribed in clinical

med-icine are morphine, trieperidine, codeine and

methadone. Heroin (diacetylmorphine), the most

commonly abused narcotic, available only

illicit-ly, is not prescribed in clinical practice. After

in-jection, it is hydrolyzed to morphine which

pro-duces its pharmacological action. While mor-phine and heroin are absorbed only following par-enteral administration, some narcotics are ab-sorbed readily from the gastrointestinal tract as well as after injection (methadone, codeine,

me-peridine). Regardless of the mode of

administra-tion, narcotics taken by a pregnant addict readily

pass the placental barrier and are capable of pro-ducing effects on the infant in utero

and

after birth.

Pregnancy in the narcotic addict has become a

significant medical and social problem in the

United States. With an estimated 500,000 narcotic

addicts, weighted heavily in the age group 17 to

30 years, there is now a sizable population of

pregnant addicts and their offspring challenging

the skills of obstetricians, pediatricians and public health workers.22

With the advent of methadone-substitution

treatment of heroin addiction, accidental

poison-ing of children by methadone has become an

in-creasingly common pediatric emergency.

Metha-done also appears as a “street” drug

and may thus

be abused by itself or in conjunction with heroin

or other drugs.

This discussion will focus on (1) the accidental

poisoning of children by methadone and (2) the

in-fant born to the heroin addict or to the woman

maintained on methadone during pregnancy.

ACCIDENTAL

METHADONE

POISONING

At present, methadone maintenance therapy of

heroin addiction appears to be one of the most

sat-isfactory forms of treatment of heroin addiction. ‘

With approximately 85,000 adults in methadone

maintenance programs, and others using the drug

illicitly, its importance in accidental poisoning of

children poses a serious problem, particularly in

urban centers.22 Accidental poisoning of children

by methadone has been reported in New York

(7)

1974;54;324

Pediatrics

Donald G. Corby and Walter J. Decker

Management of Acute Poisoning With Activated Charcoal

Services

Updated Information &

http://pediatrics.aappublications.org/content/54/3/324

including high resolution figures, can be found at:

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml

entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or in its

Reprints

http://www.aappublications.org/site/misc/reprints.xhtml

Information about ordering reprints can be found online:

(8)