Antivenom administration

B. Specific drugs and antidotes. For patients with documented envenomation, be prepared to administer specific antivenom. Virtually all local and systemic manifestations of envenomation improve after antivenom administration. Caution Life-threatening anaphylactic reactions may occur with antivenom administration, even after a negative skin test. 

B. Before skin tests or antivenom administration, insert at least one and preferably two secure intravenous lines. 

B. Delayed hypersensitivity (semm sickness) may occur 1-3 weeks after antivenom administration, the severity depending on the total quantity of antivenom administered. 

B. Pretreatment before antivenom administration. Give 50 mg (children, 0.5-1 mg/kg) IV if possible, it should be given at least 15-20 minutes before antivenom use. 

Figure 2. Effect of antivenom administration on plasma disposition of Vipera aspis venom in experimentally envenomed rabbits. Five rabbits were intramuscularly injected with 700 pg.kg of I-labelled Vipera aspis venom. Seven hours later, they were intravenously injected with 2.5 ml of Ipser Europe serum diluted with 2.5 ml of saline. Plasma samples were analyzed by ELISA for their content in free antigens (O) and by counting radioactivity for their total concentration of antigens ( ).

The effect of antivenom administration on the kinetics of Vipera aspis envenomation was also examined. Radiolabelled Vipera aspis venom was injected intramuscularly to mimic the route of administration in case of accidental envenomations. The use of a radiolabelled venom allowed the quantification of plasma venom components free and bound to antivenom antibodies. Free venom proteins were detected by ELISA. The plasma concentration time profile of venom in antivenom-treated animals is shown in Figure 2. The plasma concentration curves measured by counting radioactivity or by ELISA superimposed before the administration of the antivenom. After intravenous injection of 125 mg of IPSER Europe serum, the total venom concentrations in plasma rapidly increased more than ten-fold and remained elevated during three days, whereas the plasma levels of free venom antigens measured by ELISA rapidly decreased and remained undetectable for the same period of time. Antivenom Fab 2 administration therefore results in the immunocomplexation of venom proteins in the vascular compartment and in the plasma redistribution of venom antigens from the extravascular compartment to the vascular compartment. 

Clinically, mamba bites may not provoke a major local reaction. If neurotoxins are injected by the bite, clinical symptoms appear within minutes to hours. Clinical signs of impairment of neuromuscular transmission (ptosis, ophthalmoplegia, bulbar symptoms, or generalized weakness) dictate administration of antivenom (Ludolfph, 2000). For Elapidae (coral snakes) venom is known that is a potential neurotoxin and may cause paresthesias, weakness, cranial nerve dysfunction, confusion, fasciculations, and lethargy. Often mild local findings, diplopia, ptosis, and dysarthria are common early symptoms. Patients die because of respiratory paralysis. In these cases, early and aggressive... 

Antivenom treatment can be complicated by early reactions (anaphylaxis), pyrogenic reactions, or late reactions (serum sickness-type). The incidence and severity of early reactions is proportional to the dose of antivenom and the speed with which it enters the blood stream (1,2). These reactions usually develop within 10-180 minutes of starting antivenom therapy. The reported incidence of early reactions after intravenous antivenom in snakebite patients, which ranges from 43% (3) to 81% (4), appears to increase with the dose and decrease when refined antivenom is used and administration is by intramuscular rather than intravenous injection. Unless patients are watched carefully for 3 hours after treatment, mild reactions can be missed and deaths misattributed to the envenoming itself. In most cases symptoms are mild urticaria, nausea, vomiting, diarrhea, headache, and fever however, in up to 40% of cases severe systemic anaphylaxis develops, with bronchospasm, hypotension, or angioedema. However, deaths are rare (5). 

It is important to evaluate the clinical presentation of the patient as well as laboratory data to determine and guide the administration of antivenom. However, antivenom is not required in all patients who are envenomated and may not be necessary if there is no significant tissue swelling, systemic symptoms are absent, and laboratory parameters are normal. 

Pepin, S., Lutsch, C., Grandgeorge, M., and Scherrmann, J.M. (1997) Snake F(ab )2 antivenom from hyperimmunized horse pharmacokinetics following intravenous and intramuscular administration in rabbits. Pharmaceutical Research, 12, 1470 1473. 

D. If antivenom is used in a patient wiUi a positive skin test, pretreat with intravenous diphenhydramine (see p 436) and cimetidine (or another H2 blocker see p 428), and have ready at the bedside a preloaded syringe containing epinephrine (1 10,000 for intravenous use) in case of anaphylaxis. Dilute the antivenom 1 10 to 1 1000 before administration, and give each vial very slowly at first (ie, over 30- 5 minutes), increasing the rate of infusion as tolerated. 

I. Pharmacology. To produce the antivenom, horses are hyperimmunized with Latrodectus mactans (black widow spider) venom. The lyophilized protein product from pooled equine seta contains antibodies specific to certain venom fractions, as well as residual serum proteins such as albumin and globulins. After intravenous administration, the antivenom distributes widely throughout the body, where it binds to venom. 

VI. Dosage and method of administration. Generally, one vial of antivenom is sufficient to treat black widow envenomation in adults or children. 

B. Pretreatment before administration of animal serum-derived antivenoms or antitoxins, especially in patients with a history of hypersensitivity or with a positive skin test. Diphenhydramine can be combined with cimetidine or another Hj histamine receptor blocker. 

The phenomenon of plasma sequestration and redistribution has been observed for digitalis, colchicine and phencyclidine after Fab infusion (Smith et al, 1976 Sabouraud et al, 1992 Valentine et al, 1994). Such experiments could also be used to determine the optimal route for serum administration, to test the efficiency of a precocious or a delayed serotherapy, to define the dose of antivenom for optimal efficacy and to compare the relative effectiveness of different preparations of antivenoms. Studies similar to those carried out in the case of viper envenomations could be performed in the case of envenomations by other snakes or by scorpion stings and would help to rationalize antivenom treatment. 

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