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Comprometimento respiratório secundário a acidente ofídico crotálico (Crotalus durissus)

Authors:
Carlos Faria Santos Amaral
Carlos Faria Santos Amaral
Renato Almeida Magalhães
Renato Almeida Magalhães
Renato Almeida Magalhães
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Nilton Alves de Rezende at Federal University of Minas Gerais
Nilton Alves de Rezende
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Abstract

São analisados três pacientes que apresentaram comprometimento da função respiratória após acidente por Crotalus durissus. As manifestações respiratórias surgiram nas primeiras 48 horas após a picada do ofídio e consistiram de dispnéia, taquipnéia, uso da musculatura acessória da respiração (casos 1 e 2) e batimento das aletas nasais (caso 2). Dois pacientes (casos 1 e 2) apresentaram insuficiência respiratória aguda. O diagnóstico desta complicação no caso 1 foi clínico pois o paciente apresentou apnéia. O paciente do caso 2, 24 horas após o acidente ofídico apresentou dificuldade respiratória intensa e períodos de apnéia sendo intubado, permanecendo em respiração espontânea. Houve agravamento dos sinais clínicos de insuficiência respiratória e a determinação de pH e gases do sangue arterial mostrou em relação ao exame inicial elevação da pressão parcial de gás carbônico (40 mmHg para 50,3 mm Hg) caracterizando insuficiência ventilatória aguda. Ambos foram tratados com emprego de ventilação artificial mecânica, tendo o paciente do caso 1 permanecido no ventilador durante 33 dias e o do caso 2 durante 15 dias. Ambos desenvolveram insuficiência renal aguda, necessitaram de diálise peritoneal e recuperaram a função renal. A paciente do caso 3, apesar dos sintomas e sinais de comprometimento respiratório não apresentou alterações do pH e gases arteriais. Espirometria realizada 58 horas após o acidente mostrou capacidade vital forçada (CVF) e volume espirado no primeiro segundo (VEF1) abaixo do previsto (60 e 67% respectivamente). As espirometrias realizadas nos dias subseqüentes evidenciaram melhora progressiva destes parâmetros. No 10º dia após o acidente constatou-se aumento de 20% da CVF e de 17% do VEF1 comparativamente ao exame inicial. A relação entre VEF1 e a CVF manteve-se praticamente inalterada e em valores próximos ao previsto, caracterizando distúrbio ventilatório do tipo restritivo. O comprometimento respiratório nestes pacientes foi atribuído à ação da crotoxina na musculatura respiratória desde que não se encontravam presentes outras condições etiológicas que pudessem ocasioná-lo como uremia avançada, atelectasias, infecção pulmonar, hipopotassemia, congestão e edema pulmonar agudo.Three patients presented respiratory abnormalities following Crotalus durissus snakebite. These abnormalities appeared in the first 48 h after the snake bite and consisted of dyspnea, tachypnea, use of accessory muscles of respiration (cases 1 and 2) and flaring of the nostrils (case 2). Cases 1 and 2 developed acute respiratory failure. Case 2, 24 h after the snakebite presented difficult breathing and periods of apnea. He was intubated in the emergency room and transferred to the intensive case unit where he arrive with spontaneous breathing. His respiratory pattern worsened and measurement of arterial pH and blood gases showed metabolic and respiratory acidosis with partial carbon dioxide pressure increasing from 40 to 50,3 mmHg compatible with acute ventilatory failure. Both patients needed mechanical ventilation. Weaning from the ventilator was accomplished after 33 days in case 1 and after 15 days in case 2. Both patients also presented acute renal failure treated with peritoneal dialysis with full recovery of the renal function. Measurements of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV 1.0) was carried out 58 hours after the snakebite in case 3. Both FVC and FEV 1.0 were reduced in relation to the predicted values (60 and 67% respectively) but the ratio FEV 1.0/FVC was in the normal range. These findings were compatible with a restrictive pattern of ventilatory failure. Serial measurements showed progressive increase of both FVC and FEV 1.0 reaching 72 and 79% of the predicted values, respectively, in the 10 th day after the snakebite. Case 1 developed deep coma attributed to cerebral hypoxia suffered during several episodes of seizure and died of pulmonary infection 10 months after the snakebite. Cases 2 and 3 recovered completely. These respiratory abnormalities were attributed to the action of crotoxin in the respiratory muscles since the patients did not present complications such as severe uremia, atelectasis, pulmonary infection, cardiac failure and pulmonary edema that could also produce them.
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... The favorable outcome in this case, with extubation occurring slightly over 12 hours after intubation, may be attributed to the efficacy of the Butantan Institute-produced antivenom serum. Several studies have demonstrated the effectiveness of specific antivenoms against Crotalus durissus 7,9,12 . In a study by Amaral et al. 12 , plasma levels of total venom, crotoxin, and antivenom measured over time revealed the efficacy of antivenom treatment. ...
... Although rarely documented in the literature, respiratory muscle paralysis can occur and is a serious manifestation requiring prompt identification and treatment 9,10 . Adequate treatment with a specific antivenom typically reverses the symptoms without sequelae 10 . ...
... Adequate treatment with a specific antivenom typically reverses the symptoms without sequelae 10 . Severely poisoned patients without timely access to intubation and mechanical ventilation are at risk of asphyxia due to poison-induced peripheral respiratory paralysis [9][10][11] . ...
Early-Onset Respiratory Muscle Paralysis in Crotalic Envenomation: A Case Study
Article
Full-text available
  • Nov 2023
  • REV SOC BRAS MED TRO
Crotalic envenomation is responsible for approximately 8%-13% of ophidism cases in Brazil, yet it is associated with the highest mortality among snakes. We describe the case of a patient bitten by a rattlesnake who developed ventilatory muscle paralysis within hours after envenomation. While diaphragmatic paralysis is a rare late neurotoxic event following crotalic envenomation, in this case, paralysis occurred early but was rapidly reversed after antivenom administration. This report discusses potential contributing factors based on a comprehensive literature review. Keywords: Crotalus; Respiratory failure; Antivenom
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... Treating these conditions involves supportive care, mechanical ventilation, and antivenom therapy. Few studies have examined pulmonary involvement in snakebite accidents [4,7,19], and the pathogenesis of respiratory failure by Crotalus durissus cascavella venom has not been fully elucidated. However, respiratory failure is frequently associated with ALI, mechanical distress, and respiratory muscle paralysis [20]. ...
... In crotalic accidents, the crotoxin can compromise neuromuscular function, blocking the transmission of neurotransmitters and impacting diaphragm muscle function, which may result, clinically, in muscle paralysis and respiratory failure [4,23,24]. Other toxins, such as lectins [25,26] and serine proteases [27], as well as hypotensive components [28,29], can act synergetically to potentialize diffuse coagulation in the small and larger veins, as observed in the present study. ...
Pathophysiological and Clinical Significance of Crotalus durissus cascavella Venom-Induced Pulmonary Impairment in a Murine Model
Article
Full-text available
  • Apr 2023
Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 animals intraperitoneally inoculated with saline solution in the control group (CG), as well as venom in the experimental group (EG). The animals were euthanized at predetermined intervals (1 h, 3 h, 6 h, 12 h, 24 h, and 48 h), and lung fragments were collected for H&E and Masson histological analysis. The CG did not present inflammatory alterations in pulmonary parenchyma. In the EG, interstitial and alveolar swelling, necrosis, septal losses followed by alveolar distensions, and areas of atelectasis in the pulmonary parenchyma were observed after three hours. The EG morphometric analysis presented pulmonary inflammatory infiltrates at all time intervals, being more significant at three and six (p = 0.035) and six and 12 h (p = 0.006). The necrosis zones were significant at intervals of one and 24 h (p = 0.001), one and 48 h (p = 0.001), and three and 48 h (p = 0.035). Crotalus durissus cascavella venom induces a diffuse, heterogeneous, and acute inflammatory injury in the pulmonary parenchyma, with potential clinical implications for respiratory mechanics and gas exchange. The early recognition and prompt treatment of this condition are essential to prevent further lung injury and to improve outcomes.
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... Respiratory failure is also a rare complication from C. durissus snakebites, being associated with severe cases of envenomings resulting from paralysis of the rib cage and diaphragm muscles (148,149). A previous report on two cases of C. d. terrificus snakebite showed that respiratory manifestations emerged within the first 48 hours and were characterized by dyspnea, tachypnea, use of accessory muscles of respiration, and decreased blood pH and imbalanced pO 2 pCO 2 levels (148). ...
... Respiratory failure is also a rare complication from C. durissus snakebites, being associated with severe cases of envenomings resulting from paralysis of the rib cage and diaphragm muscles (148,149). A previous report on two cases of C. d. terrificus snakebite showed that respiratory manifestations emerged within the first 48 hours and were characterized by dyspnea, tachypnea, use of accessory muscles of respiration, and decreased blood pH and imbalanced pO 2 pCO 2 levels (148). SINAN database analysis revealed that the frequency of this complication ranged from 0% in C. d. marajoensis to 2.4% in C. d. ruruima envenomings. ...
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... Respiratory failure is also a rare complication from C. durissus snakebites, being associated with severe cases of envenomings resulting from paralysis of the rib cage and diaphragm muscles (148,149). A previous report on two cases of C. d. terrificus snakebite showed that respiratory manifestations emerged within the first 48 hours and were characterized by dyspnea, tachypnea, use of accessory muscles of respiration, and decreased blood pH and imbalanced pO 2 pCO 2 levels (148). ...
... Respiratory failure is also a rare complication from C. durissus snakebites, being associated with severe cases of envenomings resulting from paralysis of the rib cage and diaphragm muscles (148,149). A previous report on two cases of C. d. terrificus snakebite showed that respiratory manifestations emerged within the first 48 hours and were characterized by dyspnea, tachypnea, use of accessory muscles of respiration, and decreased blood pH and imbalanced pO 2 pCO 2 levels (148). SINAN database analysis revealed that the frequency of this complication ranged from 0% in C. d. marajoensis to 2.4% in C. d. ruruima envenomings. ...
Crotalus Durissus Ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinology
Article
Full-text available
  • Jun 2021
Crotalus durissus ruruima is a rattlesnake subspecies mainly found in Roraima, the northernmost state of Brazil. Envenomings caused by this subspecies lead to severe clinical manifestations (e.g. respiratory muscle paralysis, rhabdomyolysis, and acute renal failure) that can lead to the victim’s death. In this review, we comprehensively describe C. d. ruruima biology and the challenges this subspecies poses for human health, including morphology, distribution, epidemiology, venom cocktail, clinical envenoming, and the current and future specific treatment of envenomings by this snake. Moreover, this review presents maps of the distribution of the snake subspecies and evidence that this species is responsible for some of the most severe envenomings in the country and causes the highest lethality rates. Finally, we also discuss the efficacy of the Brazilian horse-derived antivenoms to treat C. d. ruruima envenomings in Roraima state.
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... In Minas Gerais state, C. d. terrificus is the most frequently encountered subspecies from C. durissus. Several clinical studies have reported acute renal failure as the leading cause of death in this type of accident, however, acute respiratory failure, due to respiratory muscle paralysis, can also account for lethality (Amaral et al., 1986;Amaral and Magalhães, 1991). ...
Engineered protein containing crotoxin epitopes induces neutralizing antibodies in immunized rabbits
Article
  • Feb 2020
Crotoxin (Ctx) is the main lethal component of Crotalus durissus terrificus venom. It is a neurotoxin, composed of two subunits associated by noncovalent interactions, the non-toxic acid subunit (CA), named Crotapotin, and the basic subunit (CB), with phospholipase A2 (PLA2) activity. Employing the SPOT synthesis technique, we determined two epitopes located in the C-terminal of each Ctx subunit. In addition, 3 other epitopes were mapped in different regions of Ctx using subcutaneous spot implants surgically inserted in mice. All epitopes mapped here were expressed together as recombinant multi-epitopic protein (rMEPCtx), which was used to immunize New Zealand rabbits. Anti-rMEPCtx rabbit serum cross-reacted with Ctx and crude venoms from C. d. terrificus, Crotalus durissus ruruima, Peruvian C. durissus and Bothrops jararaca (with lower intensity). Furthermore, anti-rMEPCtx serum was able to neutralize Ctx lethal activity. As the recombinant multiepitopic protein is not toxic, it can be administered in larger doses without causing adverse effects on the immunized animals health. Therefore, our work evidences the identification of neutralizing epitopes of Ctx and support the use of recombinant multiepitopic proteins as an innovation to immunotherapeutics production.
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Acidentes laquéticos na Amazônia brasileira: aspectos clínicos e ecoepidemiológicos
Article
  • Mar 2024
Objetivo: O presente artigo tem como objetivo descrever e discutir os aspectos mais relevantes do envenenamento por Lachesis na Amazônia brasileira. Metodologia: Assim, foi utilizada a estratégia de busca definida nas bases de dados Lilacs, Scielo e Pubmed. Esta busca permitiu a discussão dos seguintes temas: (1) biologia das serpentes do gênero Lachesis, (2) ecologia e epidemiologia do acidente laquético, (3) patogênese, (4) história natural e apresentação clínica, (5) diagnóstico diferencial, (6) avaliação laboratorial, (7) abordagem terapêutica e (8) profilaxia e controle. Resultados: O veneno laquético apresenta atividade proteolítica, hemorrágica e coagulante, sendo também relatada ação neurotóxica, com ocorrência de alterações clínicas relacionadas. As condutas devem ser adotadas com base nas informações obtidas por meio de anamnese completa, observação clínica detalhada e exames laboratoriais (principalmente tempo de coagulação). O soro antilaquético (ALS) ou soro antibotrópico-laquético (ABLS) precisa ser administrado o mais precocemente possível, o que tem um impacto positivo na evolução clínica. Conclusão: Medidas preventivas devem ser adotadas, minimizando o risco de encontro entre Homo sapiens e Lachesis e, consequentemente, a ocorrência de envenenamento. ABSTRACT Introduction: Ophidism – synonymous with snakebites – comprises envenomation cases resulting from snakebites. These cases are divided into four basic types in Brazil: bothropic, crotalic, elapidic, and laquetic. Objective: This article aims to describe and discuss the most relevant aspects of envenomation by Lachesis in the Brazilian Amazon. Methodology: To fulfill the objective, a literature review was conducted using the search strategy defined in the Lilacs, Scielo, and Pubmed databases. This search allowed the discussion of the following topics: (1) biology of snakes of the genus Lachesis, (2) ecology and epidemiology of laquetic accidents,(3)pathogenesis, (4) natural history and clinical presentation, (5) differential diagnosis, (6) laboratory evaluation, (7) therapeutic approach, and (8) prophylaxis and control. Results: Laquetic venom presents proteolytic, hemorrhagic, and coagulant activity, with reported neurotoxic action and related clinical alterations. Conducts should be based on information obtained through complete anamnesis, detailed clinical observation, and laboratory tests (especially coagulation time). Antilaquetic serum (ALS) or antibothropic-laquetic serum (ABLS) should be administered as early as possible to promote a positive impact on the victim's clinical evolution. Conclusion: Preventive measures should be adopted to minimize the risk of encounters between Homo sapiens and Lachesis and, consequently, the occurrence of envenomation. Keywords: Amazon; Lachesis; Pathogenesis; "Surucucu".
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Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids
Article
Full-text available
  • May 2020
Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite.
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Evaluation of systemic inflammatory response and lung injury induced by Crotalus durissus cascavella venom
Article
Full-text available
This study investigated the systemic inflammatory response and mechanism of pulmonary lesions induced by Crotalus durissus cascavella venom in murine in the state of Bahia. In order to investigate T helper Th1, Th2 and Th17 lymphocyte profiles, we measured interleukin (IL) -2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) and interferon gamma (IFN-γ) levels in the peritoneal fluid and macerated lungs of mice and histopathological alterations at the specific time windows of 1h, 3h, 6h, 12h, 24h and 48h after inoculation with Crotalus durissus cascavella venom. The data demonstrated an increase of acute-phase cytokines (IL-6 and TNF) in the first hours after inoculation, with a subsequent increase in IL-10 and IL-4, suggesting immune response modulation for the Th2 profile. The histopathological analysis showed significant morphological alterations, compatible with acute pulmonary lesions, with polymorphonuclear leukocyte (PMN) infiltration, intra-alveolar edema, congestion, hemorrhage and atelectasis. These findings advance our understanding of the dynamics of envenomation and contribute to improve clinical management and antiophidic therapy for individuals exposed to venom.
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South and Central American Snakes
Chapter
  • Jun 2017
Snakebites can cause life-threatening injuries, sometimes requiring intensive care. The most important snakebites occurring in Latin America are provoked by species of the family Viperidae (Bothrops, Crotalus, and Lachesis) and Elapidae (genus Micrurus). Viperid venoms induce prominent local tissue pathology, which may lead to permanent sequelae and systemic disturbances associated with coagulopathies, bleeding, hemodynamic alterations, and acute kidney injury. Elapid snake venoms, and South American rattlesnake venoms, induce neurotoxic manifestations associated with paralysis of various muscles, including respiratory muscles. Treatment of envenomation is based on parenteral administration of antivenoms. Severely envenomed patients need an adequate life support therapy such as treatment of shock, assisted ventilation, and renal therapy replacement.
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Snakebite envenomation in Central and South America. In: Critical Care Medicine (Brendt et al., Eds.), Springer International, Switzerland, pp. 1-22.
Chapter
Full-text available
  • Oct 2016
Snakebites can cause life-threatening injuries, sometimes requiring intensive care. The most important snakebites occurring in Latin America are provoked by species of the family Viperidae (Bothrops, Crotalus, and Lachesis) and Elapidae (genus Micrurus). Viperid venoms induce prominent local tissue pathology, which may lead to permanent sequelae and systemic disturbances associated with coagulopathies, bleeding, hemodynamic alterations, and acute kidney injury. Elapid snake venoms, and South American rattlesnake venoms, induce neurotoxic manifestations associated with paralysis of various muscles, including respiratory muscles. Treatment of envenomation is based on parenteral administration of antivenoms. Severely envenomed patients need an adequate life support therapy such as treatment of shock, assisted ventilation, and renal therapy replacement.
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Poisonous snakebite: a review. II. Symptomatology and treatment
Article
  • Apr 1976
  • J Fla Med Assoc
Methods of treatment of poisonous snakebite continue to be controversial. Even the efficacy of such time honored first aid measures as the use of a tourniquet, incision and suction has been questioned and denounced. Their use, however, is of definite benefit and justified after bites by North American pit vipers, if done within 30 minutes after the accident. Antivenin, the mainstay of treatment, should be given in adequate amounts, preferably intravenously, within 4 hours after the bite and over a period of one hour or less. Only then will it have beneficial effects not only on systemic envenomation but also on the local manifestations. Cryotherapy, early primary fasciotomies, steroids and antihistamines have no place in the early phases of treatment. Excisional therapy should only be considered (if at all) if it can be done within 30 minutes. All patients should receive tetanus prophylaxis, and broad spectrum antibiotics are recommended in all but the mildest cases.
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Clinical Manifestations of Cobra Bite in the Thai Farmer
Article
  • Feb 1979
Twenty cases of cobra bite in farmers from the central region of Thailand are reported. Ptosis is the earliest sign of cobra bite and is an important diagnostic indication of systemic poisoning. Restlessness, irregular breathing and mental confusion are warning signs of respiratory paralysis. Antivenom for cobra bite was administered intravenously together with symptomatic and supportive treatment; 19 patients survived and 1 died from cerebral anoxia.
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Myonecrosis, myoglobinuria and acute renal failure induced by South American rattlesnake (Crotalus durissus terrificus) envenomation in Brazil
Article
  • Feb 1985
  • TOXICON
The venom of the Brazilian rattlesnake Crotalus durissus terrificus is know to have hemolytic and neurotoxic physiopathological activities which may cause acute renal failure with hemoglobinuria and/or methemoglobinuria. As far as we know, no report has been published on the ability of the venom of this rattlesnake species to cause rhabdomyolysis. In the present paper we demonstrate that the venom of Brazilian snakes of the genus Crotalus can induce systemic myonecrosis. Clinical, laboratory and anatomo-pathological data for two patients referred to the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, 24 hr after a rattlesnake bite, are presented. In both cases, exaggerated elevation of serum levels of the enzymes creatine phosphokinase, lactate dehydrogenase and glutamic-oxaloacetic transaminase were detected, as well as data suggesting acute hypercatabolic renal failure. Immunoelectrophoresis of the serum and urine of these patients, carried out against specific anti-myoglobin serum (Behringwerke), demonstrated myoglobinemia and myoglobinuria, confirming injury to muscle tissue. Electron microscopy of a calf muscle biopsy taken from the leg contralateral to the bite from one patient revealed foci of myonecrosis.
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Afibrinogenemia secundária a acidente ofídico crotálico (Crotalus durissus terrifícus)
  • C.F.S. AMARAL
  • N.A. REZENDE
  • T.M.G. PEDROSA
  • O.A. SILVA
  • E.R.P. PEDROSO