ANAPHYLAXIS

A NAPHYLAXIS#{176} is an acute reaction,

J-

self-lim-ited symptoms to a grave medical

emer-gency. It is caused by a variety of agents,

usually occurs unexpectedly, frequently is

iatrogenic, and can be fatal if not treated

promptly and appropriately. Every

physi-of administration. Generally, agents

admin-istered parenterally are more apt to result

in severe life-threatening or fatal

anaphy-lactic reactions than those ingested orally or

administered topically to mucus

mem-branes. Medications administered orally,

such as aspirin or penicillin, however, have

cian’s and dentist’s office, pediatric

out-patient clinic, hospital emergency room,

allergy clinic or allergy testing

labora-tory, and radiology department should be

equipped to treat this potential disaster.1 i. Ai&ioti,a:

The Committee on Drugs of the

Amen-can Academy of Pediatrics has reviewed

the equipment and procedures necessary to

treat this emergency, and offers this guide

Penicillin and its semisynthetic derivatives Cephalosporins (Keflex, Kafocin, Loridine,

Keflin) Chloramphenicol Colycin

to physicians. Kanamycin

CLINICAL PICTURE _StreptomycinPolymyxin B Anaphylaxis is usually characterized by

the following sequence of signs and

symp-toms : generalized flush, urticaria,

paroxys-ma! coughing, severe anxiety, dyspnea,

Tetracyclines

Troleandomycin (Cyclamycin, TAO) Vancomycin (Vanocin)

Amphotericin B (Fungizone)

Biologicats:

wheezing, orthopnea, vomiting, cyanosis, Forei Serums (Antitoxins, Antilymphocyte

and shock. The sooner symptoms develop

after the initiating stimulus the more intense

the reaction. Symptoms beginning within

15 minutes after administration of. the

incit-Globulins [A.L.G.I) Chymotrypsin

Gamma-Globulin Asparaginase

Polypeptide Hormones (ACTH, TSH, Insulin)

ing agent require the most expedient man- Influenza Vaccine

agement.

The primary cause of death in the child is

laryngeal edema. In the adult, cardiac

ar-rhythmias may be superimposed on acute

Tetanus Toxoid

Measles and other egg-based vaccines 3. Injectable Medications:

Iron Dextran (Imferon) Dextran

upper airway edema.’ Methylergonovine Maleate (Methergine)

Nitrofurantoin MAJOR CAUSES OF ANAPHYLAXIS _{4. Local Anesthetics}

Table I lists the most common agents

as-sociated with anaphylaxis in children. The

severity and acuteness of onset will depend

upon both the type of agent and the route

5. Asiirin (Acetylsalicylic Acid) 6. DiagnoStiC Agents:

Todinated contrast media Sulfobromophthalein (B.S.P.)

Hymenoptera Stings (Bee, Yellow-Jacket, Wasp,

0 In this report, anaphylactic reactions (which

result from specific allergy, i.e., prior sensitization )

and anaphylactoid reactions (which do not require

prior sensitization and can occur on the first ad-ministration of a substance ) are combined since the clinical picture and management are identical.

and Hornet)

8. Azz,.gic Extracts (Skin-testing and treatment

solu-tions)

Foods (Especially eggs, nuts, cottonseed, and shell-fish)

io. Intravenous Narcotics (Heroin)

The statements presented herein do not preclude alternatives which may be more appropriate, taking

into account local situations and all other relevant facts.

AMERICAN

ACADEMY

OF

PEDIATRICS

COMMITTEE ON DRUGS

ANAPHYLAXIS

TABLE I

MAJOR CAUSES OF ANAPHYLAXIS8

Executive Board, AAP

TABLE II

PRIMARY EQUIPMENT AND MEDICATIONS FOR

ANAPRYLAXIS TO BE KEPT BY ALL PHYSICIANS IN AN EMERGENCY KIT

A. Tourniquet

B. 1-mi and 5-mi disposable syringes

C. Oxygen tank and mask

D. Epinephrine Solution (Aqueous) 1:1,000

E. Diphenhydramine (Benadryl), Injectable 50 mg/mI

been associated with fatal reactions so that

the oral route cannot be utilized with

impu-nity.

Before administration of substances such

as are listed in Table I, the physician

should inquire carefully for a history of

re-actions. If the patient thinks he is allergic to

a drug, it would be preferable to select an

alternate drug if possible. If there is a

possi-bility of sensitivity to foreign proteins such

as horse serum or egg based vaccines, or to

penicillin, skin testing for immediate

hyper-sensitivity to the agent should be

per-formed prior to its therapeutic

administra-tion. Since even skin testing may induce

anaphylaxis, such testing should be done

carefully with emergency equipment on

hand. Vaccines containing foreign proteins

should be diluted 1 : 100 with saline for skin

testing and penicillin should be diluted to

1,000 units per ml. The intracutaneous

in-jection of 0.01 ml of the material into the

forearm should be preceded by a

prelimi-nary scratch test. A wheal 5 mm greater

than the saline control should be

consid-ered evidence of allergy and an indication

for an alternate preparation. Skin testing is

of little value in predicting anaphylactic

sensitivity to human gamma-globulin, local

anesthetics, aspirin, or to most diagnostic

agents listed in Table I.

MANAGEMENT OF ANAPHYLAXIS

Recognizing the early signs of

anaphy-laxis will save valuable minutes.’ By

initiat-ing treatment early, the life-threatening

stages of anaphylactic shock may be

avoided or minimized. The physician

should always have basic emergency

equip-ment available to treat this condition. The

quantity of equipment, and medication to

be kept on hand for immediate therapy of

anaphylaxis, will depend upon the location

of the practice and the secondary support

available to the physician. For example, the

physician who is located miles from the

nearest hospital, or the allergist who is

more likely to encounter anaphylaxis, needs

more equipment than the physician

attend-ing patients within a medical center who

can summon an emergency team within

minutes.

PRINCIPLES OF THERAPY

In anaphylaxis there is a massive release

into the cardiovascular system of allergic

mediator substances, including histamine,

slow reactive substance of anaphylaxis

(

complement fractions such as

anaphyla-toxin. These substances cause generalized

vasodilation and urticaria, increased

vascu-lar permeability induce bronchospasm, and

produce glottid and subglottid edema. This

TABLE III

SUPPORTING EQUIPMENT AND MEDICATION

FOR

These should be available within minutes though not neces-sar-ily in the primary emergency unit:

A. Intravenous infusion sets B. Intravenous needles

C. Laryngoscope with interchangeable pediatric and

adult blades

D. Oral airway-Infant to adult E. Apparatus to establish airway patency

1. No. 1 needles for temporary airway

2. Endotracheal tubes (Numbers 18, Q, Q6, and 30 French)

3. Cricothyrotomy Tube or Tracheotomy setup F. Suction apparatus

G. Bag resuscitator for assisted ventilation7’8 (Re-susci Folding bag, P.M.R. or Ambu bag) H. Sterile surgical cutdown set

I. Aminophylline Solution (Injectable) 5 mg/mi J. Hydrocortisone/hemi succinate (Solucortef) or

equivalent

K. 5% glucose in isotonic saline (two 500 ml bottles) L. Metaraminol bitartrate (Aramine) 1% for

apy.

TABLE IV

Os’vIoNAL EQUIPMENT AND SUPPLIES

FOR ANAPHYLAXIS

These items are desirable, but may be available only in a well-equipped emergency room or intensive care unit:

A. EKG Monitor B. Defibrillator

C. Calcium Gluconate 10% (parenteral) D. Digoxin (Lanoxin) 0.Q5 mg/mi

E. Diazepam (Valium), injectable 5 mg/mI

F. Lidocaine (Xylocaine) % with 1:1,000

epi-nephrine for injection

G. Lidocaine (Xyiocaine) 2% for injection H. Sodium bicarbonate 8.75 gm in 50 ml

results in upper and lower airway

obstruc-tion, a fall in blood pressure, and usually in

vomiting which may present an additional

hazard of aspiration pneumonia.

Therapy designed to counter these factors

may thus be divided into three stages:

1. immediate Therapy. To be initiated

with any patient presenting the early signs

of anaphylaxis.

2. Supportive Therapy. For patients who

have not responded to the immediate

ther-apy.

3. Therapy of Complications. For those

few patients who have developed the most

severe complications on anaphylaxis :

oc-elusion of the upper airway, cardiac

ar-rhythmias, or severe derangement of

acid-base balance.

The physician should monitor the patient

for the following manifestations:

1. Upper Airway Obstrttction. One of the

most dramatic aspects of acute anaphylaxis

in the pediatric age group is frequently

overlooked, though pharyngeal and uvular

edema develops acutely in children and is

readily visible. The pharynx should be

ob-served frequently. At the first sign of upper

airway obstruction an oral or endotracheal

airway should be inserted.

2. Lower Airway Obstruction. Dyspnea,

frequently without wheezing, accompanies

anaphylaxis in children. Bronchospasm may

be so severe that wheezing is not heard

be-cause of a markedly diminished tidal

vol-ume.

3. Hypotension. Frequent blood pressure

determinations should be taken. Every

ef-fort should be made to keep pressure stable

using plasma volume expanders and

vaso-presser medications if necessary.

4.

Vomit-ing usually accompanies anaphylaxis in

children. Aspiration of gastric contents

should be anticipated.

Stage 1: Immediate Therapy

All patients with early signs of

anaphy-laxis should receive the following therapy

at once. Its prompt initiation may prevent

subsequent complications which would

re-quire further therapy. Table II lists primary

equipment and medications which should

be present in an emergency kit.

1. Tourniquet. If subcutaneous or

intra-muscular injection has been given into an

extremity, a tourniquet should immediately

be applied proximal to the site to obstruct

venous return from the injection.

2. Epinephrine. 0. 1 to 0.3 ml of 1:1,000

aqueous epinephrine should be injected

subcutaneously. An equal amount may be

injected around the site of injection or sting

to decrease absorption of antigen. If in

shock, the physician may administer 1 or 2

ml of 1 : 10,000 aqueous epinephrine

intrave-nously.

3. Oxygen. Since hypoxemia associated

with hypotension or upper airway edema

contributes to myocardial irritability and

ventricular fibrillation as major causes of

death, oxygen should be administered by

mask early in the course of anaphylaxis.

4. Antihistamines. Diphenhydramine

(

intrave-nously

(

hr) for the therapy of urticaria. Such

ther-apy should be considered of secondary

im-portance and should not delay more

thera-peutic steps.

Stage 2 Supportive Therapy

If the patient fails to respond to initial

therapy or is in shock when first seen, the

following therapy should be given

ther-AMERICAN ACADEMY OF PEDIATRICS

Table III lists the necessary supporting

equipment and medication, which need not

be in the emergency kit, but should be

readily available to the physician.

1. intravenous fluids. If the patient does

not respond promptly to the initial therapy,

intravenous fluids should be initiated

imme-diately to support blood pressure to treat

hypovolemia. In anaphylaxis, shock,

result-ing primarily from vasodilation and loss of

plasma volume should be treated by rapid

infusion of saline or other plasma volume

expanders.

2. Aminophylline solution. 7 mg/kg

di-luted in two equal volumes of saline, given

intravenously over a five- to ten-minute

pe-nod followed by 9 mg/kg/24 hr’ aids in

reversing bronchospasm and may inhibit

further mediator release from mast cells.b0

3. Adrenocorticosteroids. Have little

effect during the initial crucial few minutes

of anaphylaxis treatment and should be

used only to supplement the major

thera-peutic steps. Hydrocortisone, 7 mg/kg stat,

followed by 7 mg/kg/24 hr administered

intravenously may aid during the later

re-covery phase.

4. Metaraminal bitartrate (Aramine). If

the blood pressure fails to respond to saline,

Aramine, 0.5 mg to 5 mg (0.4 mg/kg), may

be added to the intravenous fluids, but

car-diac side effects should be closely

moni-tored.

Stage 3: Therapy of Complications

Late complications of anaphylaxis

in-dude occlusion of the airway, cardiac

ar-rhythmias, hypoxic seizures, and metabolic

acidosis. For therapy of these conditions a

hospital intensive care unit and blood gas

laboratory are essential.11 Table IV lists

equipment and supplies which are

neces-sary in the therapy of these late

complica-lions.

Detailed description of this tertiary

ther-apy is not included here, since therapy will

vary greatly with the patient’s clinical

course, and will need to be individualized

by the physician or his consultants.

Basi-cally an airway must be established, blood

gas derangements must be corrected,

aber-rant cardiac rhythms corrected, seizures

treated, and tissue hypoxemia corrected.

COMMENT

Since most anaphylaxis results from

iatro-genic causes, it may be prevented or

mini-mized by

(

)

his-tory of drug reactions prior to their

admin-istration, (2

)

biological products, and (3) testing for

hy-persensitivity prior to administering such

agents as penicillin to a patient with a

his-tory of penicillin allergy. No physician can

afford to administer a drug which can

in-duce an anaphylactic reaction without

ap-propriate emergency equipment on hand.

Finally, when an agent capable of inducing

anaphylaxis, such as an allergy vaccine or

penicillin, has been administered, the

pa-tient should be required to remain in the

immediate vicinity of the physician’s office

or Emergency Room for at least 15 minutes

so that appropriate therapy can be initiated

at the first sign of a constitutional allergic

reaction. Anaphylaxis occurs unexpectedly

and suddenly, and may occur in spite of

extensive precautions. Appropriate and

prompt therapy will increase the chances of

favorable outcome.

COMMITFEE ON DRucs

SUMNER

J.

CHARLES W. BIERMAN, M.D.

HOWARD M. CANN, M.D.

ARNOLD P. Gou, M.D.

FREDERIC M. KENNY, M.D.

Hiuus D. RILEY, JR., M.D.

IRWIN SCHAFER, M.D.

LEO S’rEiu, M.D.

CHARLES F. WEIss, M.D.

Consultants

GREGORY CHTJDZIK, Pharm.D. HARRY C. SHIRKEY, M.D.

LESTER F. SoxA, M.D.

REFERENCES

1. Van Arsdel, P. P., Jr. : Anaphylaxis and serum sickness. In Conn, H. L., ed : Current Ther-apy, Philadelphia: W. B. Saunders Co., p. 415, 1965.

anaphylaxis in man. New Eng. J. Med., 270:

597, 1961.

3. Siegel, S. C., and Heimlich, E. M. : Anaphylaxis. Pediat. Clin. N. Amer., 9:29, 1962

4. Bierman, C. W., and Van Arsdel, P. P., Jr.: Penicillin allergy in children. J. Allerg., 43: 267, 1969.

5. Frick, 0. L.: Anaphylaxis. In Gellis, S. S., and

Kagan, B. M., eds. : Current Pediatric

Therapy, Philadelphia: W. B. Saunders Co., p. 934, 1970.

6. Safar, P. : Recognition and management of air-way obstruction. JAMA, 208: 1008, 1969. 7. Manually operated emergency ventilation

de-vices. The Medical Letter, 1 1 :53, 1969. 8. Manually operated emergency ventilation

de-vices. The Medical Letter, 13:76, 1971. 9. Pierson, W. E., Bierman, C. W., Stamm, S. J.,

and Van Arsdel, P. P., Jr. : Double blind trial

of aminophylline in status asthmaticus.

Pami-ATRICS, 48:642, 1971.

10. Orange, R. P., Austen, W. C., and Austen,

K. F.: Immunologic release of histamine and

slow reactive substance of anaphylaxis from

human lung. J. Exp. Med., 134 (suppl) : 136,

1971.

11. Honashiro, P. K., and Weil, M. H. :

Anaphylac-tic shock in man, Arch. Intern. Med., 119:

129, 1967.

Acknowledgment

The Committee wishes to acknowledge the

gen-erous assistance of Dr. Paul P. Van Arsdel, Jr., Pro-fessor of Medicine and Head of the Division of Al-lergy, University of Washington School of

Medi-cine, Seattle, Washington, in the preparation of

1973;51;136

Pediatrics

Harry C. Shirkey and Lester F. Soyka

Kenny, Harris D. Riley, Jr., Irwin Schafer, Leo Stern, Charles F. Weiss, Gregory Chudzik,

Sumner J. Yaffe, Charles W. Bierman, Howard M. Cann, Arnold P. Gold, Frederic M.

ANAPHYLAXIS

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1973;51;136

Pediatrics

Harry C. Shirkey and Lester F. Soyka

Kenny, Harris D. Riley, Jr., Irwin Schafer, Leo Stern, Charles F. Weiss, Gregory Chudzik,

Sumner J. Yaffe, Charles W. Bierman, Howard M. Cann, Arnold P. Gold, Frederic M.

ANAPHYLAXIS

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