Mojave rattlesnake envenomation in southern California: A review of suspected cases

Wilderness and Environmental Medicine, 8, 89-93 (1997) ORIGINAL ARTICLE Mojave rattlesnake envenomation in southern California: A review of suspected cases DAVIDFARSTAD,MD 1 *, TAMARATHOMAS,MD 1, TONYCHOW,MD!, SEAN BUSH,MD l, and PAUL STIEGLER, MD 2 ldepartment ofemergency Medicine, Loma Linda University Medical Center, Lama Linda, CA 00000, and the 2Emergency Department, Saint Mary's Hospital, Apple Valley, CA 00000, USA To clarify whether Mojave rattlesnake (Crotalus scutulatus scutulatus) envenomations occurring in California cause typical crotalid tissue effects, pain, edema, and ecchymosis, we reviewed charts of snakebite victims at a tertiary care teaching hospital and a moderate-size community hospital. Forty-two patients were bitten within the range of Mojave rattlesnakes. Eight snakes were identified as Mojave rattlesnakes (group I); of these, four were confirmed by experts in snake identification (group la). Fifteen patients were reported bitten by other rattlesnake species (group 2), and in 19 envenomations the species was unknown (group 3). Seventy-five percent of patients in group 1 were reported to have local edema at the envenomation site compared with all of the patients in group 2. Ecchymosis was found in 25% of group 1 patients and 73% of group 2 patients. Pain was documented in only 12% of group 1 and 67% of group 2 victims. Neurotropic events, many severe, were found in 75% of group 1 patients compared with 7% of those in group 2. Although this study does not have the power to justify statistical evaluation, C. scutulatus envenomations do appear inclined to less tissue reaction. A disturbing trend toward severe neurotropic manifestations was also suggested in presumed Mojave rattlesnake envenomations. Key words: Mojave rattlesnake, Crotalus scutulatus. envenomation, rattlesnake, snakebite Introduction The Mojave rattlesnake (Crotalus scutulatus scutulatus) is considered one of the most dangerous reptiles in North America (1-3]. Envenomation by C. scutulatus is commonly believed to cause a clinical picture different from that of other North American pit vipers [4-6]. Populations of Mojave rattlesnakes are described based on the presence or absence of the protein complex, Mojave toxin, in their venom [7J. Mojave toxin is the most lethal crotalid peptide yet isolated, experimentally producing severe neurotropic effects (1,8J. Snakes possessing the Mojave toxin (type A snakes) are reported to exhibit a relative lack or even total absence of local tissue effects traditionally associated with crotalid envenomation [1,5,9-15]. Ecchymosis and tissue necrosis are reported to be particularly absent in type A Mojave envenomations [1,7]. Mojave rattlesnakes not expressing Mojave toxin (type B snakes) are characterized by hemorrhagic and proteolytic venom peptides that type A snakes often lack, and they cause local *Address for correspondence: 390 South 68th Street, Boulder, CO 80303. USA. tissue findings similar those of other North American crotalids (9,16]. The decision to administer snake antitoxin after crotalid envenomation is generally predicated on the degree of local tissue reaction. If victims of certain Mojave rattlesnake envenomations lack significant local findings, treatment paradigms involving antitoxin administration may be misleading. Our main goal was to pose the question, "Do Mojave rattlesnake bites produce local tissue effects comparable to those of other rattlesnakes in southern California?" Methods Loma Linda University Medical Center is the principal referral center for most of the known range of the Mojave rattlesnake in southern California (Fig. 1) [9,17-19]. We conducted a chart review of all snakebites occurring in the range of Mojave rattlesnakes in the medical center data base from 1978 to 1994. Also, snakebites seen at Saint Mary's Hospital in Apple Valley, California, were reviewed similarly from 1991 through 1994. Thirty-five envenomations were included from Lorna Linda and seven from Apple Valley. Roughly 70% of the snakebites in the Loma Linda 1080--6032 1997 Chapman & Hall

90 Fig. 1. Mojave rattlesnake in California. The gray area represents the approximate range. data base occurred outside the range of Mojave rattlesnakes and were excluded. Only one snakebite in the Apple Valley data base occurred outside the defined range for C. scutulatus. Interpretation of the medical record was limited to findings occurring within 24 hours after the snakebite. Charts were reviewed for evidence of local reaction after envenomation, specifically pain, ecchymosis, and swelling. Pain was defined as discomfort at the site of envenomation after the patient arrived at the hospital. Any degree of edema or ecchymosis documented on the medical record constituted a positive finding for the purpose of this study. Other selected variables included the patient's age and early neurotropic symptoms. Neurotropic symptoms were defined as paralysis, parasthesias, cranial nerve deficits, seizures, alteration in consciousness (ALOC) without identifiable intoxicant, or respiratory arrest. When available, identification of the snake was recorded. Species were confirmed only when the snake was inspected by an animal control official or herpetologist. If the medical record indicated that the treating physician believed the snake to belong to a certain species, the case was classified as suspected identification. The remaining snakes were defined as unknown species. Analysis groups included all snakes identified as Mojave rattlesnakes (group 1) and those snakes in group 1 confirmed as Mojave rattlesnakes (group la). Any envenomation in which the species was identified or confirmed as a rattlesnake other than C. scutulatus was included in group 2. Group 3 comprised snakebites by unknown species. Results Forty-two individuals were bitten in the Mojave area (Fig. 1). Of eight patients in group 1, in four the snake was confirmed by experts as a Mojave rattlesnake (group 1a). Fifteen individuals were included in group 2 after the snake Farstad et al. was identified as either Crotalus cerastus (sidewinder) or Crotalus viridis helleri (Southern Pacific rattlesnake). The remaining 19 snakes were not identified. Relevant data concerning symptoms are included in Table 1. Table 2 includes patient ages. In group 1, neurotropic findings occurred in six victims, including two in the confirmed Mojave group (group 1a). Of the two victims in group la, the first experienced paresthesia of the face and hands, received Wyeth polyvalent antivenin, and recovered without complications. The second patient had rapid onset of respiratory arrest and ALOe, requiring mechanical ventilation and repeated antivenin administration. Of the remaining four individuals in group 1 experiencing neurotropic symptoms, the first presented with respiratory failure and lethargy and required mechanical ventilation and multiple antitoxin doses. Administration of antivenin appeared to reverse the mental status alteration and motor weakness in this patient. The second patient presented with coma, respiratory arrest, and seizure activity and also received mechanical ventilation and antivenin. The third patient presented with lethargy, diplopia, and ataxia and received large amounts of antivenin. There was some evidence that the snake involved in this third envenomation was a confirmed Mojave rattlesnake. The final patient developing neurotropic symptoms in group 1 experienced facial and extremity paresthesia and again received antivenin. As observed previously in our area, many of the patients believed to be bitten by Mojave rattlesnakes developed significant elevations in creatinine kinase and rhabdomyolysis. Prolonged hospital courses in group 1 appeared related to renal failure and rhabdomyolysis rather than prolonged neurologic dysfunction. In group 2, one patient presumably bitten by a Southern Pacific rattlesnake experienced extremity paresthesia. Group 3 included four individuals with neurotropic findings, including one with ALOC and apnea, another with lethargy and severe hypotension, and two patients with extremity paresthesia. Table 1. Symptoms Variable Group J Group Ja Group 2 Group 3 (identified (confirmed (identified (not as Mojave) Mojave) as non- identified) Mojave) Total 9 4 15 19 Edema 7 (78%) 4 (100%) 15 (100%) 17 (89%) Ecchymosis 3 (33%) 1 (25%) 11 (73%) 11 (58%) Pain 1 (11 %) 0 10 (67%) 14 (74%) Neurotropic symptoms 7 (78%) 2 (50%) 1 (7%) 4 (21%)

Mojave rattlesnake envenomation Table 2. Age Patient Group 1 Group la Group 2 Group 3 age (identified (confirmed (identified (not (years) as Mojave) Mojave) as non-mojave) identified) 0-5 1 (ll%) 0 4 (27%) 4 (21%) 6-10 1 (ll%) 0 2 (13%) 2(1l%) 11-20 4 (44%) 2 (50%) 4 (27%) 2 (ll%) 21-60 3 (33%) 2 (50%) 4 (27%) 10 (53%) >60 0 0 1(7%) 1 (5%) Discussion RANGE OF MOJAVE RATTLESNAKES Ranging from southwestern Texas to southern California, Mojave rattlesnake populations contain significant variations in venom composition. In general, extreme western ranges of the Mojave rattlesnake possess individual snakes that differ not only in their predilection to express type A venom but also morphologically [9]. Western ranges of the Mojave rattlesnake contain individuals lighter in color, often described as yellow to green, giving rise to the popular slang term, "Mojave Green." Eastern ranges alternatively contain dark brown snakes [20]. Snakes ranging from central to northern Arizona, roughly in the area between Tucson and Phoenix, generally express type B venom [7,9]. The population of Mojave rattlesnakes in southern California is located primarily in the Mojave desert, a range including San Bernardino, Kern, Riverside, and Los Angeles (Antelope Valley) Counties on the desert (eastern) side of the San Gabrial, San Bernardino, and Tehachapi mountain crests [9,23-25]. The Mojave species in California are reported to contain primarily type A venom populations [9,25]. Among type A Mojave populations, differences in venom potency exist [9]. Type A populations in Texas are noted to have higher LDso values than those in western Arizona, southwestern Utah, and southern California. Because of overlapping ranges, an integradation zone exists, producing hybrids of type A and B snakes [9]. Hybrid forms of type A and B Mojave rattlesnakes possess both type A and B venom activities and have higher LDso values than type A snakes [9]. Mojave toxin has been isolated in the venom of western diamondback rattlesnakes (Crotalus atrax) and prairie rattlesnakes (c. viridis viridis). Interbreeding may in part explain variable toxicity after Mojave envenomation [23]. THE VENOM Type A Mojave rattlesnake venom is described as producing primarily neurotropic effects [1,10,15,22-25]. Mojave specimens from California differ significantly in lethality and reactlvity to commercial antivenin compared with specimens from central Arizona [25]. The C. scutulatus specimens in California possessed LD so values ranging from 0.13 mglkg to 0.33 mglkg, whereas the Arizona specimen LDso values ranged from 2.3 mglkg to 3.5 mglkg [6,26]. By comparison, the western diamondback rattlesnake, considered by many to be the most dangerous snake in the western United States is reported to have LDso values in the region of 3.71 mglkg [25]. Although Wyeth antivenin is believed to have limited activity against the neurotropic effects of type A venom, antitoxin administration is standard practice [1,17,25]. THE MOJAVE TOXIN The Mojave toxin complex responsible for the high toxicity of type A venom contains at least two major subunits, an acidic peptide, and a basic protein possessing phospholipase A 2 activity [19,27]. Increased lethality is often attributable to the presence of phospholipoase A 2 neurotoxins among crotalid venoms [9]. On mouse phrenic nerve diaphragm preparations, Mojave toxin causes immediate inhibition of neuromuscular transmission followed by excitation and eventually irreversible blockade [19]. Mojave toxin is described as an irreversible presynaptic neurotoxin [28-30]. Early, even presumptive antitoxin administration is occasionally recommended in the treatment of many exotic neurotoxic snake species [15,31,32]. Similar recommendations cannot be made for Mojave rattlesnake envenomations without further investigation [1,17,23]. Hagwood described hypotension after intravenous administration of Mojave toxin into rabbits, and Corrigan showed alterations of platelets and coagulation [33,34]. Other authors have described cardiotoxic, hemorrhagic, and anticomplement effects in animal studies involving Mojave rattlesnake venom [35 37]. MOJAVE ENVENOMATION SYNDROME Some researchers have suggested that the distinction between type A and B Mojave snake envenomation is not as significant clinically as might be expected from animal models [3,16,25]. Hardy reported 15 cases of documented Mojave rattlesnake bites in Arizona, concluding that envenomation in Arizona is clinically like that from other local rattlesnakes, including typical crotalid local effects, edema, necrosis, and bleb formation [16]. As Hardy volunteered, 14 of 15 snakes in his data were collected from type B or intermediate locations and one from a type A location. The patient from the type A location displayed minor neurotropic symptoms not seen in any other patient (eyelid ptosis) as well as local swelling without blebs or necrosis [16]. Local effects after Mojave envenomation in Hardy's data were described as follows: local swelling (100%), ecchymosis (67%), and necrosis (20%). Hypotension occurred in 91

92 20% of Hardy's subjects and abnonnal hematological tests in 50% [16]. OUR DATA Although attempts were made to eliminate as many non Mojave bites as possible, one cannot assume that group 1 contains envenomation exclusively from C. scutulatus. Range maps were constructed from previous publications and after consultation with local biologists; these maps, however, are estimations and may not reflect exact population distribution [9,22-24]. The Mojave green rattlesnake reputation has attained almost mythical proportion among residents of the Mojave desert, and many snakebites in the region are instantly attributed to C. scutulatus without proper identification. Another problem compounding the interpretation of snakebite data arises in the previously well established concept of bites without envenomation [38]. In certain species, it is believed as many as half of all defensive strikes result in negligible or no envenomation. Considering the above difficulties and the small numbers in this study, and data should be interpreted cautiously. Many researchers have concluded that type A Mojave envenomations generally exhibit some lesser degree of edema compared with those of other rattlesnakes. All 15 identified non-mojave species in the Mojave area manifested edema, as would be expected; however, 75% of group 1 patients also apparently manifested edema. To complicate matters further, all members of group la apparently had edema. Pain was rarely described in group 1 and group la, 12% and 0%, respectively. The majority of patients in group 2 and group 3 described pain, 67% and 74%, respectively. Data regarding pain are more likely to suffer from the retrospective nature of this study because of its subjective nature. Another problem concerning interpreting the pain data is suggested by the frequently altered mental status in group 1 patients. Ecchymosis, previously predicted to occur infrequently in type A Mojave populations, appeared to occur frequently in all groups. Clearly, a trend toward more serious envenomation and a higher incidence of neurologic symptoms is evident in group 1 and group 1a. The increased morbidity in group 1 and group la did not appear to be related to age (Table 2). Snakebite victims at either age extreme are known to have worse outcomes. Conclusions Based on our findings, local symptoms are unreliable in differentiating Mojave envenomation from other crotalid bites in southern California, although there appears to be a trend toward less frequent local symptoms in suspected C. scutulatus bites. It appears that local symptoms will usually Farstad et al. be a component of Mojave envenomations in California deserts; physicians, however, should not expect pain, swelling, or ecchymosis to exist in every case. Because of the small numbers in this study and the subsequent lack of statistical power, a larger prospective study is needed to settle this debate. Unfortunately, because ofthe relative lack of human population and the low prevalence of snakebites in the Mojave desert, such a study would take many years. Treatment for C. scutulatus envenomations should proceed in the standard fashion as for other crotalid bites, and antivenin should not be withheld. Despite the relative lack of effect against Mojave toxin, traditional antitoxin is probably active against other venom components, and clinical experience seems to support its use. New generation antitoxins developed using C. scutulatus venom may be available in the future [39]. Given the disturbing trend toward more severe neurotropic complications after C. scutulatus envenomation, a high index of suspicion should predicate treatment of rattlesnake victims in areas known to contain Mojave rattlesnakes. A careful search for bite marks is warranted in patients presenting with altered sensorium and shock of unknown etiology from the Mojave desert. Decisions regarding institution of antivenin therapy should take into account both the possible decrease in local tissue effects and the apparent increase in morbidity of C. scutulatus envenomation compared with that of other rattlesnakes in the Mojave desert region. References 1. Pattabhiraman, T.R, Russell, F.E. Isolation and purification of the toxic fractions of Mojave rattlesnake venom. Toxicon 1975; 13, 291-294. 2. Russell, F. Pharmacology of animal venoms. Clin Pharmacol Ther 1967; 8, 849-873. 3. Huang, S.Y., Perez, J.e., Rae1, E.D., Lieb, e., Martinez, M., Smith, S.A. Variation in the antigenic characteristics of venom from the Mojave rattlesnake (Crotalus scutulatus scutulatus). Toxicon 1992; 30, 387-397. 4. Rhoten, W.B., Gennaro, J., Jr. Treatment of the bite of a Mojave rattlesnake. J Fia Med Assoc 1968; 55, 324--326. 5. 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