Clinical aspects of snake venom poisoning in North America

Toxfcon, 1969, Vol. 7, pp . 33-37. Pergamon Press. Printed in Great Britain

CLINICAL ASPECTS OF SNAKE VENOM POISONING IN NORTH AMERICA* FINDLAY E . RUSSELL Laboratory of Neurological Research, University of Southern California School of Medicine, Los Angeles County-University of Southern California Medical Center, Los Angeles, California, U .S .A . INTRODUCTION MORE THAN 45,000 persons in the United States are known to be bitten by snakes each year (RUSSELL, 1968) . Of this number, approximately 7000 are bitten by venomous snakes and subsequently treated for snake venom poisoning (PARRISH, 1966) ; but as in most countries the actual number of bites by both the venomous and non-venomous snakes is not known . Using statistics presented by Parrish, and reflectiag upon our own experiences, one could assume that at least 8000 bites by venomous snakes occur each year in the United States, and that approximately 7000 of these result in some degree of snake venom poisoning. We limit the use of the term snake venom poisoning to those cases in which envenomation occurs, and the term snakebite to all cases of bites by snakes, whether venomous or not . It is well known that some bites by venomous snakes do not result in venom poisoning. In our series of 204 cases treated at the Los Angeles County-University of Southern California Medical Center and at other hospitals in the western part of the United States, 13 per cent of the patients bitten by venomous snakes displayed no evidence of envenomation, even though the snake's fangs had penetrated the skin . In addition, 9 per cent of the bites were so superficial that venom could not have been injected into the wounds . On the other hand, we have seen cases in which a fang has not penetrated beyond the fang orifice, but venom has been spewed onto the skin and inadvertently rubbed into the wound produced by the fang . In the present series of 204 cases, the offending snake and the number of bites were as follows : Crotalidae : Crotalus virtdfs helleri Crotalus vü-idts oreganus Crotalus viridis viridis Crotalus viridis lutosus Crotalus riridis abyssus Crotalus molvssus molossus Crotalus enyo jurvrts Crotalus tigris Crotalus rober rober Crotalus scutulatus scutulatus

73 6 3 2 1 4 1 1 l5 12

Crotalus cerastes cerastes Crotalus cerastes laterorepens Crotalus cerastes cercobombus Crotalus mitchelli pyrrhus Crotalus mitchelli stephensi Crotalus adamantcus Crotalus atrvx Crotalus horridus horridus Crotalus pricei pricei Crotalus kpidus lepldus

18 9 1 4 3 2 9 2 2 2

'The author is indebted to the American Society of Tropical Medicine and Hygiene, and the National Institute of Allergy and Infectious Diseases for travel support. 33

34

FINDLAY E. RUSSELL Crotalus basilLrcus basiliscus

1

Elapidae :

Crotalus durissus durissus Agkistrodon plscivorus Agkistrodon contortrix Agkistrodon rhodostoma Trimeresurus granlneus

2 6 2 1 I

Naja naja Nr{ja nigricollis Norechis scutatus Bungarus caeruleus Mlcruroides euryxanthus

Sistrurus cotenatus edwardsü Sistrurus raves

I 1

Viperidae :

Bothrops atrox

3

Vipera russelli Yipera berus Bitis lachesis

4 I 1 l

3 2 1 1

Obviously, some of these snakes are not indigenous to the United States . Approximately 20 per cent of the patients were herpetologists, zoo or snake farm personnel, or persons involved in milking snakes. In 45 per cent of the cases the offending snake has been captured and brought to the Medical Center . This percentage increases each year, probably as a result of education, as well as an awareness in our area that species specific antivenins prepared in rabbits and goats are available for those patients sensitive to horse serum. A second reason for encouraging capture of the snake, if this can be done without danger, is that after milking the reptile we can obtain a general idea as to the amount of venom that may have been injected. In milking over 5000 snakes during the past two decades we have obtained data, similar to that recorded by ICi.nusm (1956), which are of value in determining the amount of venom a snake of a certain length, age, etc. might have at a particular time of the year. The offending snake is thus milked and the data obtained on milking, along with the results of the clinical evaluation, are considered when determining the dose of antivenin to be administered . At present, approximately I S persons a year in the United States die following bites by venomous snakes . Before the advent of antivenin, about 200 persons a year in our country probably died from the bites of snakes . Obviously, some of the deaths were due to infection, but from an examination of hospital records for the years between 1900-1925, one can state that the majority of these deaths can be attributed to the venom poisoning or some complication ofthe poisoning, excluding infection. This very significant decrease in mortality can be attributed, for the most part, to the availability and early injection of antivenin, to increased education on the habits and habitats of snakes, and to a lesser degree, to more effective first-aid measures . Another significant factor is the decrease in the interval of time between the bite and the administration of the antivenin. This has been reduced from 2~6 hr to less than 1 hr during the past 3 decades. These figures are based upon a study of 300 cases chosen at random from all parts of the country. SYMPTOMS, SIGNS AND FINDINGS

The clinical manifestations of rattlesnake and coral snake venom poisoning in the United States vary with the species of elapid or crotalid involved, as well as with a number of other factors. I have discussed these findings in some detail elsewhere (RUSSELL, 1960 ; RUSSELL, 1961 ; RUSSELL, 1962 ; RUSSELL, 1966a ; RUSSELL, 1967; RUSSELL, 1968 ; DowLU~rc et al., 1968), and will limit the present discourse to the problem of the tissue destruction produced by the venom of the rattlesnake. The tissue changes, which are caused by certain cytolytic proteins, chiefly enzymes, are the most dramatic manifestations provoked by the North American crotalid venoms . Figure 1 shows the severe tissue changes at 4 days following an envenomation by an adult Crotales horridus horridus. Figure 2 shows the damage at 8 days following the bite of

Clinical Aapects of Snake Venom Poisoning in North America

35

an adult Crotales atrox, and Figure 3 shows the changes at 6 days following a Crotales viridis helleri envenomation. Similar changes are seen following bites by Crotales adamanteus, which appears to produce even more extensive local tissue damage (McCoLi,ouax and GsrrAxitO, 1963), and following some other Crotales viridis subspecies. Lesser tissue reactions are usually seen following poisonings by Crotales cerastes, Crotalua molosses molosses, Crotales mitchelli, Crotales lepidus lepidus, Crotales rober rober, Crotales basiliscus basiliscus and Agkistrodon piscivores. The venom of Crotales scutulatus, while the most lethal of the North American rattlesnake venoms (and even though it produces considerable swelling and edema), causes only minimal tissue destruction . Poisonings by Agkistrodon contortrix usually result in far less tissue change and rarely in any tissue loss. USE OF ANTIVENIN

Of particular importance is the time and amount of antivenin injected . The early administration of this antitoxin cannot be overemphasized . The choice of antivenin, the route of injection and the amount to be given will depend upon the species and size of snake involved, the point of envenomation, the size of the patient and other factors (KLAUHSR, 1956; RossSS,, 1962; RUSSS,L and LAURITZEN, 1966). In the United States, one polyvalent antivenin is commercially available for envenomations by the Crotalidaethe rattlesnakes, copperheads and cottonmouths (water moccasins) . This product, Antivenin (Crotalidae) Polyvalent, Wyeth, is a lyophilized powder of relined horse serum. While it does not give equal protection against the venoms of all North, Central and South American rattlesnakes, it does give very good protection against most species, and good protection against all but a few. Figure 4 shows the left hand of a 4-year-old child who, from the initial symptoms and signs, appeared to have been severely envenomated by a 140 cm Crotales tuber tuber. She received 6 vials of antivenin (Crotalidae) Polyvalent i.v. over a 30-min period within 2 hr of the bite, 1 vial intramuscularly within 30 min of the bite and a second vial i.m . 3 hr and 30 min after the bite. In spite of the marked swelling and edema 8 hr following the injury (Fig. 4), there was little ecchymosis and no necrosis or tissue loss. The edema and swelling began to recede within 12 hr after the bite, and the hand returned to normal size and color at 5 days. I would attribute the good result to the prompt and adequate dose of antivenin given. Figure 5 shows the left hand of a 21-year-old snake handler who had been bitten on the index finger by a 130 cm Crotales viridis oregamtis, while force feeding the snake. The patient went into shock 10 min following the bite . The snake was milked and found to have 52 mg (dry weight) of venom. Normally, a snake this size would possess 125 mg. The i.v. Ln~ in mice of this snake's venom was 184 mg per kg body weight. The patient received 5 vials of Antivenin (Crotalidae) Polyvalent i.v. over a 30-min period, and 1 vial of antivenin i.m., all within 1 hr of the bite. Although the swelling and edema extended into the arm, it quickly abated during the first day. When the picture was taken, S8 hr following the bite, the minimal swelling was limited to the affected finger and the dorsum of the hand. Again, I would attribute the good result to the prompt and adequate dose of antivenin injected . Figure 6 shows the left forearm of a 17-year-old girl who had been bitten 6 hr previously by a 122 cm Crotahas viridis helleri. The patient was seen at the Medical Center within 20 min of the poisoning. At that time she complained of tingling around the mouth, over the scalp and at the finger tips. The affected extremity was painful, and there was tenderness

36

FINDLAY E. RUSSELL

in the left axilla . The patient also complained of weakness, nausea and headache . Pulse was 120 and weak ; blood pressure was 90/60 mm, and respiratory rate was 28. The patient was given an i.v. course of a species-specific antivenin prepared in goats, as she was found to be sensitive to horse serum. Six hr following the bite the patient was asymptomatic. The picture also shows the `typical' fang marks produced by the North American pit vipers . FOLLOW-UP CARE

Often neglected but of the utmost importance is the follow-up care. Figure 7 shows the hand and forearm of the patient bitten by Crotalus horridus horridus following the second surgical debridement ; this was at 7 days. It is our practice to surgically remove the vesicles and superficial necrotic tissue between the sixth and ninth days following the bite. Most of the tissue changes will have occurred by the fourth to sixth days, but all surgical procedures should be avoided during this initial period . Interruption of the vesicles or superficial necrotic tissues between the second and sixth days may result in further tissue injury and bleeding. On the other hand, the debridement should not be delayed beyond a week or 10 days, since once the injured tissues or blood have organized, debridement is more difficult. I have found that there is a period of time, between the sixth and ninth days, when surgical removal of the affected tissues can be carried out without diflîculty or subsequent complications. Figure 8 shows the hand and forearm of the patient previously noted (Figs . 1 and 7) at 6 weeks following the envenomation . The patient's extremity had been kept in sterile, loose, absorbent, dry dressings. He was maintained on a broad-spectrum antibiotic . Patients with this amount of tissue destruction must be placed nn antibiotics, and these I usually start on the third day following the bite. In a small series of cases 1 have found that tissue regeneration appears to be stimulated by metronidazole (RUSSELL, 19666). It has long been the practice at our Medical Center to initiate physical therapy early in the course of rattlesnake venom poisoning. At the present time, I begin both passive and active exercises the day following the first surgical debridement. One to 2 days following this, the injured part is exercised daily in a whirlpool bath containing hexylresorcinol . Thereafter, the physical therapist spends 1 hr a day with the patient, and also gives him an additional hour of exercises to do by himself. I believe this program has been responsible for our low incidence of contractures and deformities. We have had oily 3 minor contractures in the past 15 years. The thumb of the hand shown in Figs. 1, 7, and 8 had to be rebuilt primarily because of a persistent infection which warranted several surgeries. One of the other contractures was also due to surgical procedures necessitated by infection. We have had no amputations or deaths in our own series of patients, but we have amputated several limbs in cases referred to us 8 to 10 days following the envenomation . In all of these cases the injured limb had been packed in ice for 6 to 9 days . There appears to be little doubt that in these cases the amputation was made necessary by the cryotherapy and not by the venom poisoning. Figure 9 shows the foot and leg of one such patientjust prior to amputation below the knee. A final measure which should be tried in cases where there is extensive tissue destruction is hyperbaric oxygen. Doctors Workman, Woolley and I have placed 3 patients with considerable tissue necrosis from venom poisoning under oxygen therapy for a total of 30 days, and have been very much encouraged by the extent of the healing. We feel that this therapeutic tool, when available, should be utilized during the period when tissue regeneration is proceeding without complications.

FIG. ~ .

HAND AND FOREARM OF PATIENT BI7TEN HY CfOIOIGS horrtdus hofridus.

Tox. f.p . 36

FIG.

2.

FOQT AND

LEG GF

CHILD

HTTTEN

BY

C~OIRIdS CJtïUX .

FIG. 3.

FINGER OF CHILD BITTEN BY Gotalets viridis he!leri .

Ftc . 4.

HAND OF CHILD

BITTEN

dY Crotalus neber ruber.

FIG . S .

FINGER OF SNAKE HANDLER BII"ïEN BY Crotalus viritfis oreganus .

.~, FIG .

6.

FOREARM OF

GIRL BITTEN

HY

Crota/us riridis helleri.

FIG . ~ .

HAND AND FOREARM SHOWING DEHRIDEMENT FOLLOWING BITE (FIG . I).

Crotalus korridus horrtdus

FIG. S.

SAME EXTREMITY (FIG. L â11d 7) Ô WEEKS FOLLOWING ENVENOMATION .

FIG . 9,

FOOT AND LEG OF CHILD ON PROGRAM OF CRYOTHERAPY,

Clinical Aspects of Snake Venom Poisoning in North America Acknowledgement-The author wishes to thankDr . shown in Fig. 2.

R. L. Px~cFrt of Guymon, Oklahoma

37 for the photograph

REFERENCES H. G., MINTON, S. A., Jß ., and RussELL, F. E. (1968) Poisonous Snakes ojthe World, 212 pp. Washington, D.C . : Government Printing Ot~ce. KLAUBER, L. M. (1956) Rattlesnakes. Their Habits, Life Histories, andInfluence on Mankind, 2 vols .,1476 pp . Berkeley : University of California Press. MC~OLLOUGH, N. C. Snd GENNARO, J. F., Jn . (1963) Evaluation of venomous snake bite in the southern United States from parallel clinical and laboratory investigations. J. Fla. med. Ass. 49, 959. PARRLSH, H. M. (19C~ Incidence of treated snakebites in the United States. Publ, Hlth Rep., Wash, gl, 269. RUSSELL, F. E. (1960) Rattlesnake bites in Southern California. Am . J. nud. Sci. 239, 1 . RUSSELL, F. E. (1961) Injuries by venomous animals in the United States . J. Am. med. Ass. 177, 903. RUSSELL, F. E. (1962) Snakevenom poisoning. In : Cyclopedia ojMedicine, Surgery andtheSpecialties, Vol. II, p. 197, (PERSOL, G. M., Ed .) . Philadelphia : Davis. RUSSELL, F. E. (1966a) Injuries by venomous animals. Am . J. Nurs. 66, 1322 . RUSSELL, F. E. (19666) Metronidawle in snakevenompoisoning. Meets Inst. Butantes Simp. Internac. 33, 845. RUSSELL, F. E. (1967) Pharmacology of animal venoms . Clür . Pharmac. 7Trer. S, 849. RUSSELL, F. E. (1968) In : Current Therapy, p. 830, (Coax, H. F., Ed,) . Philadelphia : Saunders. RUSSELi,, F. E. and L~urerrzEx, L. (1966) Antivenins . Tress. R. Soc. trop. Med. Hyg. 60, 797. DOWLING,