Diphtheria Antitoxin (Equine)
Indications And Clinical Uses: For the treatment of suspected or confirmed cases of diphtheria.
Precautions: Before administering any serum or antitoxin to a patient, physicians are well advised to ascertain whether the patient has a history of asthma, or hay fever, and particularly, whether the patient suffers distress when in proximity to horses. Patients with such a history may develop serious reactions of an anaphylactic character upon the administration of serum of equine origin either s.c., i.m. or i.v. It should be borne in mind, also, that a patient who has been given a previous injection of serum of equine origin may develop a marked reaction when given a second injection, especially if the previous injection was i.v.
At the time of administering any serum or antitoxin to a patient, it is desirable to have 1 mL of epinephrine HCl solution (1:1 000) immediately available.
Tests for Sensitivity to Serum or Antitoxin: A test for sensitivity to serum or antitoxin should be carried out each time a serum or antitoxin is administered, unless it is being given daily. Sensitivity to any particular serum or antitoxin may be gauged by one of the following methods.
Skin or eye tests for sensitivity should be done before any injection, regardless of whether or not the patient has had the serum previously. The skin test dose is 0.1 mL of a 1:100 saline dilution of the serum to be given intracutaneously. In persons with a history of allergy, the dose is reduced to 0.05 mL of a 1:1 000 dilution, intracutaneously. The reaction is read in 5 to 30 minutes and is positive if a wheal with a hyperemic areola appears.
(In a marked reaction the wheal is likely to have irregular projections.) The extent of the wheal and of its projections, and the dimensions of the hyperemic area provide a rough index of the degree of the patient’s sensitivity, and of the resultant likelihood of his reacting unfavorably to the injection of the particular serum or antitoxin concerned.
A negative skin test does not entirely preclude the possibility of the occurrence of serum reactions.
Except in small children, an eye test often is simpler and is less likely to show nonspecific reactions. A drop of a 1:10 dilution of serum in physiologic saline is instilled in one eye, controlled by a drop of physiologic saline solution in the other eye; a positive reaction consists of lacrimation and conjunctivitis appearing in 10 to 30 minutes.
Eye tests have not been known to be fatal, but skin tests have resulted in fatalities. Therefore, a serum should never be injected, nor a skin test performed unless a syringe containing 1 mL of epinephrine HCl solution (1:1 000) is within immediate reach.
Serum Reactions: 1. Anaphylactic Reaction: In the event of a reaction of an anaphylactic character, 0.5 mL of epinephrine HCl solution (1:1 000) should be administered by the s.c. or i.m. route.
2. Thermal Reaction: When this reaction occurs, it usually develops from 20 minutes to 1 hour after the injection of serum or antitoxin. It is characterized by a chilly sensation, slight dyspnea and a rapid rise in temperature.
3. Serum Sickness: The symptoms of serum sickness are fever, skin rashes, edema of the skin, glandular enlargement and pains in the joints. These symptoms may appear individually, or in combination, within 14 days after the administration of a serum or antitoxin. Urticarial reaction is usually relieved by a s.c. or i.m. injection of 0.5 mL of epinephrine HCl solution (1:1 000). In severe cases of serum sickness ACTH or cortisone may be required.
It has been recommended that 0.3 mL of epinephrine HCl solution (1:1 000) be administered not only to every patient who gives a positive reaction to a sensitivity test, or has received serum or antitoxin before, or has a history of allergy, but to every patient before receiving serum irrespective of these factors.
Dosage And Administration: Treatment of Diphtheria: Since diphtheria antitoxin injected i.m. is absorbed much more rapidly than when injected s.c., i.m. injections are greatly superior to s.c. injections in the treatment of diphtheria. In the treatment of diphtheria, results are best when very large doses of antitoxin are administered. In an uncomplicated pharyngeal case, the dose should not be less than 20 000 IU for a child or 40 000 IU for an adult. In laryngeal or severe toxic cases, or in cases left untreated for several days much larger doses amounting to 100 000 or even 150 000 units are recommended. Such circumstances call for a combination of i.m. and i.v. injections, and the use of from 10 000 to 20 000 units i.v. is recommended. Diphtheria antitoxin as distributed by the Connaught Laboratories Limited may be quite satisfactorily used i.v., at a 1:10 dilution. It should be at ambient temperature before being injected.
Administration of Antitoxin to Sensitive Persons: Whenever there is a history of allergy, sensitivity to horse serum or manifestations of sensitivity when in proximity to horses, or if the reaction to the skin or eye test is positive, great care must be exercised in the administration of serum (or antitoxin).
No one method can be advised for the administration of serum or antitoxin for sensitive persons as each presents an individual problem. Desensitization of the patient should be carried out by serial injections of diluted antitoxin as indicated below at intervals of 20 minutes, provided no reaction occurs.
Schedule for Desensitization: (a) 0.05 mL of 1:20 dilution s.c., (b) 0.1 mL of 1:10 dilution s.c., (c) 0.3 mL of 1:10 dilution s.c., (d) 0.1 mL undiluted serum s.c., (e) 0.2 mL undiluted serum s.c., (f) 0.5 mL undiluted serum s.c., (g) inject remaining therapeutic doses i.m.
After the patient can properly withstand these doses of serum or antitoxin, it is usually safe to inject larger doses (i.m.) at 20-minute intervals.
If a reaction occurs after a desensitizing dose, injections should be stopped for 1 hour, recommencing the schedule at 20-minute intervals by repeating the last dose which failed to cause a reaction.
If deemed imperative on clinical grounds, i.v. administration of a serum or antitoxin may be commenced after the purpose of the desensitization has been satisfactorily served. The first i.v. dose should be small, however, i.e., 0.1 mL diluted with 10 mL of sterile physiological saline, and it should be injected very slowly, 1 mL/minute. Increasingly larger doses may then be similarly given at half-hourly intervals.
A separate sterilized syringe and needle should be used for each individual patient to prevent transmission of homologous serum hepatitis and other infectious agents from one person to another.
Note: Following the administration of serum (or antitoxin), and particularly in those cases showing a positive skin or eye test, the patient should be kept under close observation for 1 to 2 hours and under reasonably close surveillance for a period of 24 hours.
The site of injection should be prepared with a suitable antiseptic.
If sterile disposable syringes and needles are not used, syringes and needles should be sterilized in an autoclave 121°C for 30 minutes. If this method of sterilization is not available syringes and needles should be boiled for at least 20 minutes. Care should be taken to maintain sterility until used.
Withdrawing the preparation from a rubber-stopped vial: Do not remove the rubber stopper from the vial.
Apply a sterile pledget of cotton moistened with a suitable antiseptic to the surface of the rubber stopper and allow it to act for at least 5 minutes. Draw into the sterile syringe a volume of air equal to the amount of the preparation to be withdrawn from the vial. Pierce the centre of the rubber stopper with the sterile needle of the syringe; invert the vial; slowly inject into it the air contained in the syringe; and, keeping the point of the needle immersed, withdraw into the syringe the required amount of the preparation. Then hold the syringe-plunger steady and withdraw the needle from the vial.
The person giving the immunization should record the dose, route of administration, date of immmunization and the antitoxin lot number on the patient’s immunization card or medical record.
Availability And Storage: Each vial contains: 20 000 IU of a refined and concentrated preparation of globulins obtained from horse serum modified by enzymatic digestion. Also contains phenol 0.22% as a preservative. Note: The volume of antitoxin in a vial will vary from lot to lot. This is because the potency of the bulk antitoxin varies from lot to lot and it is therefore necessary to adjust the filling volume of each lot so that each vial contains 20 000 IU. As a result, vials from one lot may appear half full while vials from a different lot may appear three-quarters full. Store in a refrigerator between 2 and 8°C.
Diphtheria Antitoxin (Equine) Connaught Antitoxin