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Before administration of any product prepared from horse serum, appropriate measures must be taken in an effort to detect the presence of dangerous sensitivity: (1) A careful review of the patient's history, including any report of (a) asthma, hay fever, urticaria, or other allergic manifestations; (b) allergic reactions upon exposure to horses; and (c) prior injections of horse serum. (2) A suitable test for detection of sensitivity. A skin test should be performed in every patient prior to administration, regardless of clinical history.

Skin test-Inject intracutaneously 0.02 to 0.03 mL of a 1:10 dilution of Normal Horse Serum or Antivenin. A control test on the opposite extremity, using Sodium Chloride Injection, USP, facilitates interpretation. Use of larger amounts for the skin-test dose increases the likelihood of false-positive reactions, and in the exquisitely sensitive patient, increases the risk of a systemic reaction from the skin-test dose. A 1:100 or greater dilution should be used for preliminary skin testing if the history suggests sensitivity.

A positive reaction to a skin test occurs within five to thirty minutes and is manifested by a wheal with or without pseudopodia and surrounding erythema. In general, the shorter the interval between injection and the beginning of the skin reaction, the greater the sensitivity. If the history is negative for allergy and the result of a skin test is negative, proceed with administration of Antivenin as outlined above. If the history is positive and a skin test is strongly positive, administration may be dangerous, especially if the positive sensitivity test is accompanied by systemic allergic manifestations. In such instances, the risk of administering Antivenin must be weighed against the risk of withholding it, keeping in mind that severe envenomation can be fatal. (See last paragraph of this section.) A negative allergic history and absence of reaction to a properly applied skin test do not rule out the possibility of an immediate reaction. Also, a negative skin test has no bearing on whether or not delayed serum reactions (serum sickness) will occur after administration of the full dose.

If the history is negative, and the skin test is mildly or questionably positive, administer as follows to reduce the risk of a severe immediate systemic reaction: (a) Prepare, in separate sterile vials or syringes, 1:100 and 1:10 dilutions of Antivenin. (b) Allow at least 15 minutes between injections and proceed with the next dose if no reaction follows the previous dose. (c) Inject subcutaneously, using a tuberculin-type syringe, 0.1 , 0.2, and 0.5 mL ofthe 1:100 dilution at 1 5-minute intervals; repeat with the 1:10 dilution, and finally undiluted Antivenin. (d) If a systemic reaction occurs after any injection, place a tourniquet proximal to the site of injections and administer an appropriate dose of epinephrine, 1 :1 000, proximal to the tourniquet or into another extremity. Wait at least 30 minutes before injecting another dose. The amount of the next dose should be the same as the last that did not evoke a reaction. (e) If no reaction occurs after 0.5 mL of undiluted Antivenin has been administered, switch to the intramuscular route and continue doubling the dose at 1 5-minute intervals until the entire dose has been injected intramuscularly or proceed to the intravenous route as described above under "Dosage and Administration."

Obviously, if the just-described schedule is used, 3 to 5 or more hours would be required to administer the initial dose suggested for a moderate or severe envenomation, and time is an important factor in neutralization of venom in a critically ill patient. Wingert and Wainschel 4 have described a procedure based on the experience of their group which they have used in some severely envenomated patients who have positive sensitivity tests: 50 to 100 mg of diphenhydramine hydrochloride is given intravenously, followed by slow intravenous infusion of diluted Antivenin for 15 to 20 minutes while carefully observing the patient for symptoms and signs of anaphylaxis; if anaphylaxis does not occur, Antivenin is continued, maintaining close observation of the patient. Patients who require Antivenin but develop signs of impending anaphylaxis in spite of this or the procedure described earlier present a difficult problem, and consultation should be sought.

Systemic REACTIONS

A. The immediate reaction (shock, anaphylaxis) usually occurs within 30 minutes. Symptoms and signs may develop before the needle is withdrawn and may include apprehension, flushing, itching, urticaria; edema of the face, tongue, and throat; cough, dyspnea, cyanosis, vomiting, and collapse.

B. Serum sickness usually occurs 5 to 24 days after administration. The incubation period may be less than 5 days, especially in those who have received horse-serum-containing preparations in the past. The usual symptoms and signs are malaise, fever, urticaria, lymphadenopathy, edema, arthralgia, nausea, and vomiting. Occasionally, neurological manifestations develop, such as meningismus or peripheral neuritis. Peripheral neuritis usually involves the shoulders and arms. Pain and muscle weakness are frequently present, and permanent atrophy may develop.

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