DOSAGE AND ADMINISTRATION
Before administration, read CONTRAINDICATIONS,
PRECAUTIONS and ADVERSE
REACTIONS sections. Since the possibility of a severe immediate reaction
(anaphylaxis) exists whenever a horse-serum-containing product is administered,
appropriate therapeutic agents, including a tourniquet, airway, oxygen, epinephrine,
an injectable pressor amine, and corticosteroid, must be available and ready
for immediate use. Constant attendance and observation of the patient for untoward
reactions are mandatory when Antivenin (Crotalidae) Polyvalent (equine origin)
is administered. Should any systemic reaction occur, administration should be
discontinued immediately and appropriate treatment initiated.
The intravenous route of administration is preferred, and probably should always be used for moderate or severe envenomation. Intravenous administration is mandatory if venom-induced shock is present. To be most effective, Antivenin should be administered within 4 hours of the bite; it is less effective when given after 8 hours and may be of questionable value after 12 hours. However, it is recommended that Antivenin therapy be given in severe poisonings, even if 24 hours have elapsed since the time of the bite. It should be kept in mind that maximum blood levels of Antivenin may not be obtained for 8 or more hours after IM administration.
For intravenous-drip use, prepare a 1:1 to 1:10 dilution of reconstituted Antivenin
in Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP. To avoid foaming,
mix by gently swirling rather than shaking. Allow the initial 5 to 10 mL to
infuse over a 3- to 5-minute period, with careful observation of the patient
for evidence of untoward reaction. If no symptoms or signs of an immediate systemic
reaction appear, continue the infusion with delivery at the maximum safe rate
for intravenous fluid administration. The dilution of Antivenin to be used,
the type of electrolyte solution used for dilution, and the rate of intravenous
delivery of the diluted Antivenin must take into consideration the age, weight,
and cardiac status of the patient; the severity of envenomation; the total amount
and type of parenteral fluids it is anticipated will be given or are needed;
and the interval between bite and initiation of specific therapy.
It is important to begin administration of the entire initial dose of Antivenin
as described above as soon as possible, based on the best estimate of the severity
of envenomation at the time treatment is begun (see PIT VIPER BITES AND ENVENOMATION).
The following initial doses are recommended:3,4,5,16
no envenomation–none. minimal envenomation–20-40 mL (contents of 2 to 4 vials). moderate envenomation–50-90 mL (contents of 5 to 9 vials). severe envenomation–100-150 mL or more (contents of 10 to 15 or more vials).
These recommended initial-dosage volumes are in general accord with those of
others.10,17,18
The need for additional Antivenin must be based on the clinical response to
the initial dose and continuing assessment of the severity of poisoning. If
swelling continues to progress or if systemic symptoms or signs of envenomation
increase in severity or if new manifestations appear, for example, fall in hematocrit
or hypotension, administer an additional 10 to 50 mL (contents of 1 to 5 vials)
or more intravenously. For severe envenomation, a total of 200 to 400 mL (contents
of 20 to 40 vials) may be necessary.10,19,20,21,22 There is not a
recommended maximum dose. The total required dose is the amount needed to neutralize
the venom as determined by clinical response.23
Envenomation by large snakes in children or small adults requires larger doses of Antivenin. The amount administered to a child is not based on weight.
If Antivenin is given intramuscularly, it should be given into a large muscle mass, preferably the gluteal area, with care to avoid nerve trunks. Antivenin should never be injected into a finger or toe.
The effectiveness of corticosteroids in treatment of envenomation per se or
venom shock is not resolved. Russell3,4 and others26,27
believe corticosteroids may mask the seriousness of hypovolemia in moderate
or severe poisoning and have little, if any, effect on the local-tissue response
to rattler venoms. Corticosteroids should not be given simultaneously with Antivenin
on a routine basis or during the acute state of envenomation; however, their
use may be necessary to treat immediate allergic reactions to Antivenin, and
corticosteroids are the agents of choice for treating serious delayed reactions
to Antivenin.
Intravascular envenomation characterized by extremely rapid (i.e., within
several minutes) onset of severe signs and symptoms has occurred in rare instances.
In such cases, neutralization with Antivenin must be instituted immediately.24
Snakes' mouths do not harbor Clostridium tetani. However, appropriate
tetanus prophylaxis is indicated, since tetanus spores may be carried into the
fang puncture wounds by dirt present on skin at time of bite or by nonsterile
first-aid procedures.
A broad-spectrum antibiotic in adequate dosage is indicated if local tissue damage is evident.
Shock following envenomation is treated like shock resulting from hypovolemia from any cause, including administration of whole blood, plasma, albumin, or other plasma expanders, as indicated.
Aspirin or codeine is usually adequate for relieving pain. Sedation with phenobarbital or mild tranquilizers may be used if indicated, but not in the presence of respiratory failure.
The bitten extremity should not be packed in ice, and so-called "cryotherapy" is contraindicated.
Compartment syndromes may complicate pit viper envenomations, especially those
caused by bites on the lower extremities. Prompt surgical consultation is indicated
whenever a closed-compartment syndrome is suspected.3,4,25
Defibrination and disseminated intravascular coagulation (DIC) syndromes have
been associated with envenomation caused by some pit vipers native to the United
States, and appropriate therapy may be indicated.3,4,26,27,28,29
Technique for Reconstituting the Dried Antivenin
Pry off the small metal disc in the cap over the diaphragms of the vials of Antivenin and diluent. Swab the exposed surface of the rubber diaphragms of both vials with an appropriate germicide. With a sterile 10 mL syringe and needle, withdraw the diluent (Sterile Water for Injection, USP) from the vial of diluent and insert the needle through the stopper of the vacuum-containing vial of Antivenin. The vacuum in the Antivenin vial will pull the diluent out of the syringe into the vial. However, delivery of 10 mL of diluent may not always exhaust the vacuum in the Antivenin vial. If all vacuum is not exhausted, reconstitution may be more difficult. Therefore, either disconnect the needle from the syringe and allow room air to be pulled into the Antivenin vial until all vacuum is released from the container or withdraw the syringe with attached needle from the vial, pull 10 mL of room air into the syringe and reinsert needle with attached syringe containing room air through stopper and repeat, if necessary, to release any remaining vacuum. At the first introduction of diluent into the vaccine vial, it is important for the needle to be pointed at the center of the lyophilized pellet of Antivenin so that the diluent stream will wet the pellet. If the diluent stream is not directed at the pellet but allowed to run down the inside wall of the vial, the pellet will float up and adhere to the stopper thereby rendering complete reconstitution much more difficult. Agitate by swirling, NOT by shaking, for 1 minute, at 5-minute intervals. Shaking causes foaming and if the diluent stream is not properly directed as described earlier, pieces of the pellet may get caught in the foam and will be very difficult to wet. Complete reconstitution usually requires at least 30 minutes.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The color of reconstituted Antivenin may vary from clear to slight yellowish or greenish.
Before each administration, gently swirl the vial to dissolve the contents.
Before any Antivenin is administered, an appropriate horse-serum sensitivity
test must be done so that, in case administration of Antivenin is subsequently
required, a decision on how to proceed will have been made (see PRECAUTIONS).
HOW SUPPLIED
Each combination package contains one vacuum vial to yield 10 mL of Antivenin
(with preservatives: phenol 0.25% and thimerosal [mercury derivative]
0.005%) and one 1 mL vial of normal horse serum (diluted 1:10) as sensitivity
testing material with preservatives: thimerosal (mercury derivative) 0.005%
and phenol 0.35%.
Store original, unused (not reconstituted) vials at temperatures not exceeding 98°F (37°C) -Do not freeze.
Reconstituted Antivenin should be used as soon as possible but may be
used up to 4 hours after reconstitution (but not yet diluted) if stored at 36°F
to 46°F (2°C to 8°C).
Antivenin which has been reconstituted and then diluted should be used
immediately. Any remaining after 12 hours or more after dilution should be discarded.
Gently swirl the vial of reconstituted Antivenin before each administration.
REFERENCES
2. PARRISH, H.: Incidence of treated snakebite in the United
States. Pub. Hlth. Rep. 81:269, 1966.
3. RUSSELL, F. et al: Snake venom poisoning in the United States.
Experiences with 550 cases. JAMA 233:341, 1975
4. RUSSELL, F.: Venomous bites and stings: Poisonous snakes.
In The Merck Manual of Diagnosis and Therapy, pp. 2450-2456, 14th Ed., 1982.
5. WINGERT, W. and WAINSCHEL, J.: Diagnosis and management of
envenomation by poisonous snakes. South. Med. J. 68:1015, 1975.
6. PARRISH, H. & HAYES, R.: Hospital management of pit viper
venenations. Clinical Toxicol. 3:501, 1970.
7. McCOLLOUGH, N. & GENNARO, J.: Diagnosis, symptoms, treatment
and sequelae of envenomation by Crotalus adamanteus and Genus Agkistrodon. J.
Florida Med. Assoc. 55:327, 1968.
8.WATT, C. & GENNARO, J.: Pit viper bites in South Georgia
and North Florida. Tr. South. Surg. Assoc. 77:378, 1966.
9. SEILER, J. et al: Venomous snake bite: Current concepts of
treatment. Orthopedics 17(8):707, 1994.
10. RUSSEL, F.: Snake venom poisoning. Scholium International, Inc., New York,
1983.
17. WINGERT, W.: Rattlesnake bites. West. J. Med. 140:100, 1984.
18. PICCHIONI, A. et al: Management of poisonous snakebite. Vet. Hum. Toxicol.
26:139, 1984.
19. ARNOLD, R.: Rattlesnake venoms, their actions and treatment. Edited by
Anthony Tu. Marcel Dekker Inc., New York, 1982. pp. 315-338.
20. ARNOLD, R.: Treatment of venomous snakebites in the Western Hemisphere.
Military Med. 149:361, 1984.
21. WATT, C.: Treatment of poisonous snakebite with emphasis on digit dermotomy.
South. Med. J. 72:694, 1985.
22. HENNESSEE, J.: Snakebite treatment. South. Med. J. 77(2):280, 1984.
23. WINGERT, W. & CHAN, L.: Rattlesnake bites in Southern California and
rationale for recommended treatment. West. J. Med. 148(1):37, 1988.
24. DAVIDSON, T.: Intravenous rattlesnake envenomation. West. J. Med. 148(1):45,
1988.
25. GARFIN, S. et al: Rattlesnake bites: Current concepts. Clin. Orthop. 140:50,
1979; Role of surgical decompression in treatment of rattlesnake bites. Surg.
Forum 30:502, 1979.
26. VAN MIEROP, L.: Snakebite symposium. J. Florida Med. Assoc. 63:101,
1976.
27. ARNOLD, R.: Treatment of snakebite. JAMA 236:1843, 1976; Controversies
and hazards in the treatment of pit viper bites. South. Med. J. 72:902,
1979.
28. VAN MIEROP, L. & KITCHENS, C.: Defibrination syndrome following bites
by the Eastern diamondback rattlesnake. J. Florida Med. Assoc. 67:21,
1980.
29. SABBACK, M. et al: A study of the treatment of pit viper envenomization
in 45 patients. J. Trauma 17:569, 1977.
Wyeth Laboratories: A Wyeth-Ayerst Company, Marietta, PA 17547,
USA. Revised September 4, 2001. FDA Rev date: n/a