Botulism Antitoxin Trivalent Types A, B and E (Equine)
Connaught
Antitoxin
Indications And Clinical Uses: Experimental evidence concerning the amount of circulating antitoxin needed to counteract botulism toxin poisoning by antitoxin therapy is not fully documented. The outcome of treatment depends, as it does in other comparable conditions, largely on the time interval elapsing after onset of symptoms before the peak of absorbed antitoxin is reached. This principle is illustrated in recently reported animal experiments.
Clinical trials of type E botulism antitoxin in Canada and in Japan showed that dosages of not more than 5 000 IU of type E antitoxin, administered as a rule i.v., proved remarkably efficacious. The product, as distributed, contains 8 500 IU of E per vial, an amount which, if evenly distributed without loss throughout the blood stream, theoretically provides an adequate circulating titre.
Since the mouse-protective value of one IU of types A and B antitoxin is several times that of one IU of type E antitoxin, the relative proportions of types A and B present in the mixture are believed to be adequate to establish a level of neutralizing capacity in the blood stream, against the homologous toxins, of several times the level shown to be clinically efficacious for type E antitoxin. One or more vials of this mixture may be necessary to provide adequate circulating antibody of each type, depending upon the severity of the toxemia.
Precautions: Precautionary Measures in the Administration of any Serum or Antitoxin: 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. in character.
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 hyperaemic 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 hyperaemic 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 reactions are 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: Prevention of Botulism Types A, B, and E: The recommended prophylactic dose for an individual who has eaten food suspected of being infected with C. botulinum is 1 500 to 7 500 IU of Type A, 1 100 to 5 500 IU of Type B and 1 600 to 8 500 IU. Type E given i.m. depending on the amount of food eaten (one-fifth to one vial). This may be followed in 12 to 24 hours by the injection of the contents of a second vial if any signs or symptoms of botulism appear.
Treatment of Botulism Types A, B and E: The best results in the treatment of botulism are likely to be obtained where very large doses of antitoxin are given early in the disease. The object is to provide an excess of circulating antitoxin as early as possible.
Patients who received antitoxin in the first 24 hours after onset of signs and symptoms (early antitoxin) had a lower fatality rate (10%) than those who received antitoxin more than 24 hours after onset (late antitoxin) (15%) or those who did not receive antitoxin at all (46%). Patients who received early antitoxin had fewer days in the hospital, fewer days on a ventilator, and fewer days to sustained improvement than patients who received late antitoxin.
I.V.: In order to ensure the quickest possible neutralization of all toxin in the tissue and fluids, it is advisable to give immediately 7 500 IU of Type A, 5 500 IU of Type B and 8 500 IU of Type E (1 vial) i.v. at a 1:10 dilution. It should be at ambient temperature before being injected.
I.M.: In order to provide a reservoir of antitoxin from which it may be absorbed, an additional 7 500 IU of Type A, 5 500 IU of Type B and 8 500 IU of Type E (1 vial) may be given by i.m. injection.
The administration of two 5 000 IU vials of anti-ABE (15 000 IU Type A, 11 000 IU Type B, 17 000 IU Type E) (1 vial given i.v. and 1 vial given i.m.) to human subjects results in high levels of circulating antitoxins that are capable of neutralizing from 12 to 1 500 times the amount of toxin that is found in the serum of patients with botulism.
Further doses may be indicated in 2 to 4 hours if the signs and symptoms worsen. Black and Gunn found that the incidence of serum sickness in patients treated with botulism antitoxin was highest for persons who received more than 4 vials (30 000 IU Type A, 22 000 IU Type B, 34 000 IU Type E).
Important Points in Injecting the Serum: I.V.: The serum is injected very slowly i.v. at a dilution of 1:10. It is advisable that the patient be tested for sensitivity to horse serum and, if necessary, initial i.v. doses should be small and well diluted (see below).
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 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 reactions occur.
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 an 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 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.
Availability And Storage: A refined and concentrated preparation of horse globulins modified by enzymatic digestion. Preservative: phenol 0.4%. Trace amounts of blood substance A and residual porcine pepsin may be present. Each vial contains: Type A: 7 500 IU. Type B: 5 500 IU. Type E: 8 500 IU. The volume per vial varies depending on the potency of the antitoxin. Store at 2 to 8°C. Do not freeze.
Botulism Antitoxin Trivalent Types A, B and E (Equine) Connaught Antitoxin
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