Reprinted from Bull. Chicago Herp. Soc. 42(7):105-115

¹ Itacaré Medical Foundation, Itacaré, Bahia State, Brazil

² Physician, Municipality of Itacaré, Bahia State, Brazil

³ Biologist, Belo Horizonte, Minas Gerais State, Brazil

⁴ Vital Brazil Hospital - Butantan Institute, São Paulo, São Paulo State, Brazil

Corresponding author:

JLC CARDOSO

Av. Vital Brazil 1500

Hospital Vital Brazil

São Paulo / SP

05503.900

Brazil

E-mail: jlcardoso@butantan.gov.br

Abstract: Confirmed snakebite accidents involving Lachesis vipers (“surucucu”) are rare in the literature. We present two cases that occurred recently in the southern region of Bahia State - Brazil. These two cases were singled out of a series of nine accidents. Both presented intense local pain, edema, mild local ecchymosis, local hemorrhage and dramatic systemic alterations within the first 30 minutes after the bite: hypotension, vomit and diarrhea, sinus bradycardia configuring a pre-chock state. Both patients were treated with antivenom within 60 minutes of the accident: one received 20 I.V. vials of Bothropic-Lachetic Antivenom ('BLA' - Butantan Institute) and the other received 10 I.V. vials of Bothropic-Lachetic Antivenom (Butantan Institute). Both patients recovered fully. Few laboratorial tests were made and both snakes were positively identified. Accidents in the north margin of the Amazon River seem to present different signs and symptoms. The objective of this case report is to contribute for a better understanding of these envenomings and of the genus as a whole, aiming at early diagnosis and treatment of Lachesis snake bites.

Keywords: Lachesis, Bushmaster, snakebite, case report, poisoning.

Introduction

Proven Lachesis-inflicted accidents are rare in scientific literature while, on the other hand, the genus is given almost mythological status by common folk. According to the Villas-Boas brothers (indigenists and field man, who dedicated most of their lives to making first contact with previously unknown indian tribes in the Amazon where `white man' had never set foot before in the late 40s), “[Lachesis] is the only venomous snake of Brazil that might actually attack a human being” (Villas-Boas, 1994). In ancient Tupi-Guarani Indian language, “surucucu” stands for “one who strikes repeatedly”(Silveira, 1982) . Exploratory expeditions to South America such as those carried on by Von Spix and Von Martius (1817-1820) brought back to Europe weird, exaggerated accounts of huge snakes attacking campfires, such as the one below, by John Manley (1851):

Figure 1: Note published in London in 1851 reporting the alleged Lachesis' “Antipathy to fire” (Manley, John 1851).

Those who actually deal with Lachesis on a daily basis, find it of “calm disposition and delicate constitution” (Boyer, 1989). However, when cornered, wounded, thermally disoriented or guarding eggs, the genus may react in a very particular way. In the words of the experienced Rob Carmichael (pers. com.):

“As far as safety goes, I never work with these snakes unless I am 100% focused and alert. I keep many elapids (including king cobras), bothrops, crotalines, etc. but nothing strikes more concern in me than these bushmasters. I fully know that a bite could end my life, which is why when I work with the bushmasters, I don't work with any other snake that day... I want to make sure that I am ready, focused, relaxed and ready for anything. So far, I have found the bushmasters to be amazingly calm and wonderful animals, however, I also have experienced first hand the full wrath of this species... Even a 16' king cobra coming full steam at me didn't scare me as much as an 8' bushmaster in full “I want to kill you” mode did a year ago. It made me completely re-think my strategies and safety procedures when working with them. But, for the most part, they have been very easy going and I think staying calm, deliberate and keeping movements slow and always working on the bushmaster's terms is the best course of action.”

This dauntless behavior, its almost mythical status and even religious associations with “the evil one” fuel the ongoing slaughter of the species. In the case of the Atlantic Bushmasters (Lachesis muta rhombeata), the destruction of 93% of its natural habitat makes it a highly endangered species, classified as “Vulnerable” by the “International Union for the Conservation of Nature”.

Case Reports

In six years in the region of Ilhéus - Bahia State - Brazil, we have positively identified eight accidents as caused by Lachesis, the most recent ones on 01/21/2007 and 02/28/2007. A ninth accident took place just before our arrival in the region and resulted in the almost instant death of J.A.D., a 7 year old boy, who went out of his impoverished house at night to pee, stepped on an animal and was bitten more than once according to the family.

If there is venom inoculation, the first 60 minutes of these accidents are always dramatic and similar to the evolution of the hypovolemic shock: severe hypotension may occur within 20 minutes, along with hypothermia as low as 35°C, vomiting, diarrhea, abdominal pain, difficulty to swallow, sensorial disorientation, sinus bradycardia, and eventually shock and cardiac arrest. Although these signs and symptoms are the norm in our experience, while reviewing the literature we found out that there is no general agreement around the onset of such signs and symptoms, something that could be explained at least in part by the difficulty in determining the genus which actually caused the accident (Hardy and Haad, 1998), specially in the Amazon area where large Bothrops atrox (Linnaeus, 1758) are commonly confused with (small) Lachesis specimens. Out of these eight cases, we chose to report only two, in which the animals are still alive, positively identified and photographed.

Case 1

T.L., professional herpetologist and Biologist, male, 23 years old, healthy, 140 pounds, was bitten on the top of his head by a 2,00m male Lachesis at 11:40 of 05/27/2005 while working with de Souza in the Serra Grande Center:

Late biochemistry (4 - 7 days after the accident, performed in Belo Horizonte/Minas Gerais State) indicating consumption of coagulation factors on the occasion of the accident and a slow recovery in the following days.

Case 2:

Patient J.A.S., male, 49 years old, professional herp keeper at CEPLAC, a federal agency for cocoa research, was bitten in the medium 1/3 of the left forearm on 10/02/2006 at 8:30am by a two meter male Lachesis fed 15 days before. Upon clinical examination, only one inoculation point was found.

J.A.S. suffers from high blood pressure and is under regular medication, but on that specific morning he reports to have forgotten to take his 25mg of Captopril - this might have saved his life.

The first symptom was severe pain, and the patient immediately drove his car for 20 minutes to a nearby hospital, where he arrived “in the limit of his strength”. Upon admission, systolic blood pressure was 70 mmHg with no detectable diastolic blood pressure. The patient also presented intense sweating, diarrhea, upper abdominal pain and great difficulty to swallow.

Infusion of saline solution 0,9% + metoclopramide + 10 I.V vials of "Bothropic-Lachetic Antivenom" (BLA - Butantan) were simultaneously administered. Coagulation time could not be measured (over 30 minutes) and remained like that for the next 24 hours, during which he had compressive bandage around the wound site. The patient developed a moderate systemic reaction to the antivenom (figure 3 below). After 24 hours of hospitalization blood pressure stabilized, bleeding at the inoculation point stopped, urinary debt was over 40 ml/hour with normal macroscopic aspect so, after another two days under observation, he was discharged for an ambulatorial follow-up. The left arm remained sore for two weeks.

Figure 3: J.A.S. back to work 14 days after the accident, handling the same animal involved in the accident

Discussion:

All confirmed accidents by Lachesis should be considered life-threatening since even mere scratches, one fang inoculations and accidents with babies or youngsters (Ripa, 2002) , characterized by small amounts of poison delivered may still provoke early systemic symptoms, something we do not observe in the sympatric Bothrops genus, where the size of the animal is the most important prognostic factor: bigger animal = more venom = more damage (Ribeiro et al., 1989). By saying this, we do not intend to affirm that the amount of venom delivered is unimportant for the clinical evolution, since in vitro, the neurotoxic action of the venom is dose-dependant. On the other hand, based on our experience, we infer the existence of a “Minimum Activating Dose” (M.A.D.) which triggers all symptomatology. It is worth noticing that this “M.A.D.” is way below the 400mg potentially delivered by adult Bushmasters.

Regarding the biochemistry of the Lachesis venom, the following activities have been described:

We believe that the so-called “activation of the parasympathic autonomous nervous system” can be considered partly neurotoxic in nature, where kinins³⁶ and phospholipases play a major role. Therefore, in Lachesis, the abnormally quick shock onset seems best explained by a Synergy Hypothesis, in which neurotoxicity, vasodilatation and leaks to interstitial space, independently play a part.

One could only speculate as the causative factor of specific clinical alterations such as dysphagia or the “vagal triad” (hypotension, diarrhea, vomiting - and why not, a fourth element: sinus bradycardia) or sensorial disorders (to colors, deafness, uncoordinated march) that will take place within 30-45 minutes after a bushmaster bite in Brazil, BUT it is not speculation to affirm that these clinical features can be considered pathognomonic of the genus that caused the accident, as noted by Jorge et al., 1997:

“A review of reports of 20 cases of bites in humans reliably attributed to this snake [Lachesis] in Costa Rica, French Guyana, Brazil, Colombia and Venezuela confirms a syndrome of nausea, vomiting, abdominal colic, diarrhea, sweating, hypotension, bradycardia and shock, possibly auto-pharmacological or autonomic in origin, not seen in victims of other American crotaline snakes.”

Bothropic accidents may lead to shock and hypotension and even death within one hour of inoculation, but such events are rare (Cardoso et al., 2003; Haad, 1980-81). Statistics of a major ER (H.P.S João XXIII) in Belo Horizonte/Brazil, show that only 5% of all bothropic accidents present hemodynamic alterations such as blood pressure drops upon admission (Cecilia Haddad, pers. com.). A series of 29 accidents involving Bothrops jararacussu (Lacerda, 1884), normally the worst bothropic accident, presented two (6,8%) hemodynamically unstable patients (Milani et al., 1997). Therefore, hemodynamic repercussion as well as all morbidity in the bothropic accident is dose-dependent. It isn't so in Lachesis, probably due to the combination of factors described above. As long as at least the “M.A.D.” is inoculated, the synergy of effects, will produce major blood pressure drops in humans with unsurpassed speed.

Our observations about how dangerous these intoxications may be in humans are in agreement with recent accidents with North American herpetologists and also with a series presented by Bolaños e Rojas in 1982 where 3 of 4 patients died, even with early (but insufficient) antivenom therapy (Ripa, 2002; Bolaños and Rojas, 1982). Adult Lachesis may reach or exceed 3.40m TL (Ditmars, 1933; Campbell and Lammar, 2004) and according to Bolaños (1972), can inoculate 333mg or more of venom (Bolaños, 1972) but, although there are usually great amounts of toxins to be neutralized, the severity of the symptoms is not necessarily related to the amount of venom injected. The unique, dose-independent body response to the overwhelming synergic hypothesis, which includes direct actions of the poison, auto-pharmacological events and individual characteristics, something also noted by other author-victim (Ripa, 2002), can be taken as a standpoint for further studies on the fundamentals of the “M.A.D.” concept.

The present work diverges of that presented by Burnheim and Souza and others ( Sá-Neto, 1995; Souza, 1999) developed in Manaus area (Amazonas State), where statistics suggest that only 15% of Lachesis accidents present the "vagal triad" as a clinical feature, probably due to (1) inclusion of "dry-bites" in their series (“only about 50% of people bitten by venomous snakes are actually envenomed”- (Warrel, 1989) ; (2) wrong information (common) by patients as to which animal caused the accident; (3) wrong classification by M.D.s (common) of the snake brought to the hospital; (4) mistakes in the application/interpretation of ELISA tests; or maybe the clinical practice of the M.D.s working in the north margin of the Amazon river is revealing a totally different pattern of venom action when compared to the Atlantic coast and north of Mato Grosso State envenomings. Here is the enigma.

Only accidents by Lachesis acrochorda (Garcia,1896) in Colombia should present low or none "vagal simptomatology" (Campbel , Lammar and Warrel, 2004), but Haad et al ( Haad, 1980-81; Hardy and Haad, 1998) presented three cases from Colombia in which “the triad” was observed. It has been experimentally proved that samples of venom from Brazil, Costa Rica, and Colombia did display toxic and enzymatic differences (Hardy and Haad, 1998; Otero et al., 1998), but all induced a qualitatively similar pathophysiological profile in vitro (Otero et al., 1998). We will comment further down (see map below) on clinical variations in Lachesis accidents in humans as described by Warrel (Campbell, Lammar and Warrel, 2004), keeping Haad and Hardy in mind: that "we are not mice". Maybe the observations (85 % of absence of "vagal symptoms") of our colleagues of the “north margin” will also fit in Warrels' observations, since the venom does present variations within populations, seasons, age of the animals (Gutierrez, 1990), and that can also lead to wrong readings of ELISA tests. Coincidentally, Ripa in his latest work proposed the extension of the range distribution of Lachesis muta rhombeata to the entire forest south of the Amazon river, and not only in the Atlantic coast (Ripa, 2002).

Our position is clear: bushmaster bites in Brazil, or at least in the south of the Amazon river and in the Atlantic rainforest, without extreme and immediate local pain and edema and without early (20 minutes) gastrointestinal (diarrhea, vomiting) and cardiovascular (hypotension) repercussion, is not a Lachesis bite. There is no such thing as “walk for two days for help”, “deny local pain” or “refuse hospitalization” if you have been bitten by a “surucucu” (and had venom injected in your organism). In one accident in Serra Grande, Bahia, January 21^st, 2007, "N.R." was knocked out by hypotension and could not make the 40 minute walk to town to get help, being saved by his wife who rushed for an ambulance right after killing the snake, extracting her tongue and forcing the husband to swallow it as an “antidote”.

Such “treatments” should be viewed as acts of despair due to the abandonment by the public health system of geographically isolated populations, until very recently. However, we've also collected in the region ethnobotanic approaches, such as the “graviola tea” (Anonna muricatta) which is now being tested for possible anti-emetic and/or vasoactive properties.

Since we are talking about the treatment of snakebites that can quickly lead to life threatening conditions, as far as treatment is concerned, the tourniquet issue inevitably arises. Such practice has not been abolished. It has saved lives in Australia and South Africa (Fairley, 1929; Chritensen, 1963) in accidents with Elapids. Taipans (Oxyuranus), “the deadliest” in popular interpretations of the LD 50 in mice, will cause systemic alterations in 3 hours, progressively worsening, reaching critical status around the 12^th hour and killing 20 hours after the bite (White, 1995) so, “their accidents” are medical emergencies like ours (Lachesis) are. However, a study in Brazil involving the use of tourniquet in accidents with Crotalus durissus (Amaral et al, 1998) proved it to be inefficient. So since we believe in the M.A.D and the instant pain reveals that it may already been delivered into the body, and an arterial tourniquet in such circumstance could only be efficient if applied within a minute or two of the accident, something hard to do, and last but not least, the procedure is controversial in Viperidae, we do not recommend its use.

In Serra Grande, we carry a kit of ampoules and syringes, ethylepinephrine cloridrate, adrenaline, atropine, metoclopramide for I.M. use and also saline solution for I.V. use; working in pairs (at least) is essential. In case 1, “T.L.” was not able to make a phone call within 15 minutes of the bite.

The field administration of the antivenom must take into consideration the impossibility of quick rescue and the feasibility of controlling eventual reactions with limited resources. Alternating (12-20 vials of 10ml ampoules) I.M. and I.V. administration to intentionally delay absorption for safety reasons (Pepin et al, 1995; Riviere et al., 1997), does not prevent the onset of complications such as major exanthem and bronchospasm, so it is wise to be ready for these medical emergencies. Allergic tests have been shown to be ineffective (Warrel, 1989). As soon as the patient makes it to the nearest hospital, signs and symptoms such as blood pressure drops, bleeding at the wound site, or the "triad" will reveal the need of more antivenom, “better late than sorry”. If none of these signs are present and the patient can be considered hemodynamically stable with proper urinary debt, it is time to face other complications edema being one of them.

Fasciotomies seem to have no indication in Lachesis bites. In Brazil, the concept of Compartment Syndrome (C.S.), an event of the first 24 hours, is still plagued with empiricism. Statistics from Vital Brazil Hospital ( França and Cardoso, 1989; Bueno, 1996) show that C.S. was observed in only 1,4% of all Bothrops accidents, locally more aggressive than Lachesis. Precise indication could avoid further expoliation, blood loss, risk of infection, longer hospitalization time, and costs. The “usually disappointing” (Warrel, 1989) results of fasciotomies can be explained, at least in part, by the lack of reliable parameters upon which the decision has to be made (compartment pressure above 45 mm Hg and doppler revealing obstruction to blood flow) and to the fact that muscle swelling and necrosis can be attributed to direct action of venom injected in the area.

The possibility of late blood pressure drops, bleeding to the digestive system and reaction to antivenom therapy demands in hospital observation for 48-72 hours and ambulatorial follow-up for the next 30 days. Infection in the wound site can turn into a major complication if deep fascial progression is undetected below normal looking skin. Common agents are: D group streptococcus, Enterobacter sp., Providencia rettgeri, Providencia sp., Escherichia coli, Morganella morganii, Clostridium sp., Aeromonas hydrophila, Proteus mirabilis, Acinetobacter alcoaceticum, Pseudomonas aeruginosa and Klebisiela pneumonae (Bolaños et al 1982; de Andrade et al 1989; Jorge et al.,1990)

Close attention also to “serum disease” around the 20th day (sore joints, fever, dermatitis), mesenteric thrombosis (Rosenthal et al., 2002) and intracranial bleeding (Eric Jennings, pers. com.) that can be of early (first 24 hours.) or late (fifth day) onset:

Figure 4: Intracranial bleeding 24 hours after a Lachesis bite, causing the death of a 23 year old man. Accident near Santarém/Pará State, in 2003. (Courtesy Dr. Eric Jennings)

Figure 5: Intracranial bleeding in a 57 year old man 5 days after a Lachesis bite; the patient survived neurosurgery. We do not know of any other cases where the patient survived intracranial bleeding in ophidism,wordlwide. Great and historical job by Dr. Jennings, again near Santarém/Pará State in 2003. (Courtesy Dr. Eric Jennings)

It is important to remember that the doses of antivenom are the same in children as in adults, and that the anti-bothropic antivenom will not neutralize the coagulant factor of Lachesis poison, so its use is not recommended (Ramza et al, 1994). Heparin has also no indication in Lachesis bites.

Conclusion:

Lachesis bites should be considered medical emergencies, regardless of the size of the animal. In Brazil, they can happen anywhere in the Brazilian Atlantic rainforest remnants, from Rio de Janeiro State up to Rio Grande do Norte State, parts of Ceará State (Feitosa et al., 1997; Freitas, 2005), possibly in "Parque do Rio Doce" or “Zona da Mata” in Minas Gerais State and in the Amazonic region as a whole. The animal is highly dependent and adapted to the preserved rainforest of medium altitude (high humidity and low temperatures).

Figure 6: Dark areas denote “Lachesis Territory”.

From the medical standpoint, the academic discussion if Lachesis should maintain its subspecific differentiation (Ripa, 2002) or should be considered as two populations of the same species (Fernades et al., 2004), is irrelevant.The present edition of rules of the "International Code of Zoological Nomenclature" (Fourth Edition, ISBN 053301-006-4) maintains the trinominal status (subspecific) for South American bushmasters, but its true that the concept of subspecies in herpetology is highly questionable.

It is of great medical importance however, to keep in mind that the venoms of both populations (coastal & amazonic) are similar (Otero et al., 1998) and the clinical features in intoxications should also be similar. However, important variations such as local effects and C.N.S. activation have been described (Campbell, Lammar and Warrel, 2004). The venom of the amazonic animal has greater hemorrhagic activity, whereas the venom of the Atlantic Rainforest animal has greater coagulant activity (Otero et al., 1998). It is not clear at this point, how these differences fit in the puzzle of the “north margin enigma”.

Whoever ventures in “Lachesis Territory” should recognize the risk, work in pairs with a pre-determined evacuation plan, carry and in remote areas carry an emergency kit similar to the one used in Serra Grande, knowing how to use it in order to avoid early and severe hypotension, and to allow oral intake of liquids or medication (blocking vomiting) while on the way to the nearest hospital.

Until the lyophilized version of the antivenom for human use reaches the Brazilian market, refrigeration between 3-8°C and respect to expiration dates dictate its effectiveness when needed. A well-planned distribution among major towns will help avoid the tragedy of late treatment: death, suffering and costs. In our series, the efficient distribution meant eight lives saved without any permanent handicap. The costs issue also leads us to affirm that tests such as ELISA are recommended but not necessary to differentiate Lachesis accidents from the others.

The statistic probability of accidents in the Amazon region, 76% Bothrops x 17% Lachesis (Ramza et al., 1994), indicate that the obvious antivenom to be distributed (and carried around) in these areas is the highly effective (Pardal et al., 2004) "Bothropic-Lachetic Antivenom" (BLA) but attending physicians in ERs in the darker areas in the map above should also keep in mind that Crotalus is also present in the Amazon and in some coastal biomes of Atlantic Rainforest (“restingas”) in Piauí state (Freitas, 2005) and that Micrurus (some without the red rings), all share the well preserved forest with Lachesis and Bothrops.

Notification of snake bites is compulsory in Brazil, but most of our statistics remain unreliable due to under-notification, general ignorance about such accidents, and work overload in underequipped and understaffed ERs, all of which might contribute to wrong planning in the distribution of the BLA throughout the vast Brazilian territory. A good example of this is an old review of medical records in the Ilhéus area that points to Lachesis accidents figures around 0,5%. Although this particular accident is uncommon due of the ecobiology of the animal and its usually calm disposition, it is not as rare this figure (0.5%) seems to indicate, as noted by Baard (Ramza et al., 1994) and in the present work.

While we watch in real time the burning down of the Amazon and the progressive destruction of the residual 7% of the Atlantic Rainforest, signaling a dire future of Lachesis in the wild, isolated actions such as the Serra Grande breeding center try to compensate the damage already done via programs that may generate animals for antivenom production, reintroduction of animals to their native habitat and advanced pharmacological research.

Figure 7: “Baby Atlantic Surucucu”, Núcleo Serra Grande, in Itacaré/Bahia State - Brasil (de Souza ,2007).

Acknowledgements:

To Dr Ronaldo Souza, our greatest inspiring and driving force in this article

To Drs. Daniela Damico from UNICAMP and Fatima Furtado from Butantan Institute, for the deep insights in the biochemistry of Lachesis venom.

To Dr Cecilia Haddad, for sharing her experience in the Toxinology Department of