Neurotoxicity of Micrurus lemniscatus lemniscatus (South American coralsnake) venom in vertebrate neuromuscular preparations in vitro and neutralization by antivenom.

We investigated the effect of South American coralsnake (Micrurus lemniscatus lemniscatus) venom on neurotransmission in vertebrate nerve-muscle preparations in vitro. The venom (0.1-30 µg/ml) showed calcium-dependent PLA2 activity and caused irreversible neuromuscular blockade in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. In BC preparations, contractures to exogenous acetylcholine and carbachol (CCh), but not KCl, were abolished by venom concentrations ≥ 0.3 µg/ml; in PND preparations, the amplitude of the tetanic response was progressively attenuated, but with little tetanic fade. In low Ca2+ physiological solution, venom (10 µg/ml) caused neuromuscular blockade in PND preparations within ~ 10 min that was reversible by washing; the addition of Ca2+ immediately after the blockade temporarily restored the twitch responses, but did not prevent the progression to irreversible blockade. Venom (10 µg/ml) did not depolarize diaphragm muscle, prevent depolarization by CCh, or cause muscle contracture or histological damage. Venom (3 µg/ml) had a biphasic effect on the frequency of miniature end-plate potentials, but did not affect their amplitude; there was a progressive decrease in the amplitude of evoked end-plate potentials. The amplitude of compound action potentials in mouse sciatic nerve was unaffected by venom (10 µg/ml). Pre-incubation of venom with coralsnake antivenom (Instituto Butantan) at the recommended antivenom:venom ratio did not neutralize the neuromuscular blockade in PND preparations, but total neutralization was achieved with a tenfold greater volume of antivenom. The addition of antivenom after 50% and 80% blockade restored the twitch responses. These results show that M. lemniscatus lemniscatus venom causes potent, irreversible neuromuscular blockade, without myonecrosis. This blockade is apparently mediated by pre- and postsynaptic neurotoxins and can be reversed by coralsnake antivenom.

Assessment of local pain and analgesia in envenoming by wandering spiders (Phoneutria spp.).

Phoneutrism (bites by wandering spiders of the genus Phoneutria) frequently results in local pain. We describe a retrospective cohort study of a case series of phoneutrism admitted to our Emergency Department (ED), in which we used the Numeric Pain Rating Scale (NPRS 0-10) to assess the intensity of local pain upon admission, and recorded the analgesic measures used to control this pain. Other criteria for inclusion were: (1) An age ≥8 years, (2) Treatment exclusively at our ED, and (3) Visualization or photographing the spider at the time of the bite and/or bringing the spider for identification. The patients were classified into three groups based on the intensity of pain at admission: group 1 - mild or no pain (NPRS: 0-3), group 2 - moderate pain (NPRS: 4-6), and group 3 - intense or severe pain (NPRS: 7-10). Fifty-two patients fulfilled the inclusion criteria (n = 11, 14 and 27 in groups 1, 2, and 3, respectively), with a median age of 37 years. The median NPRS upon admission was 7 (interquartile range: 5-8). In patients with an NPRS <7 (groups 1 and 2), only dipyrone was used to alleviate the pain, with six cases in group 1 requiring no analgesia. Most of the cases in group 3 (19/27) were treated with a local anesthetic infiltration (2% lidocaine), in association with analgesics given i.v. in 16 cases (dipyrone, 14; tramadol, 2); additional analgesic treatment was required in seven cases, six of which were treated with tramadol i.v. The median time spent in the ED was 18, 58 and 120 min for groups 1, 2 and 3, respectively. These findings show that most cases of envenoming by Phoneturia spp. involved intense local pain (NPRS ≥7), with local anesthetics being used only in these cases, often in association with dipyrone i.v.

Temporal evolution of dermonecrosis in loxoscelism assessed by photodocumentation.

BACKGROUND: Although loxoscelism (bites by brown spiders of the genus Loxosceles) frequently results in dermonecrosis, no previous clinical reports have provided detailed temporal photodocumentation of the evolution of dermonecrotic lesions in a case series. METHODS: This was a retrospective cohort study involving a case series of loxoscelism. Only cases of dermonecrosis with photodocumentation of lesion evolution (from admission until complete or almost complete healing) were included. RESULTS: Eight patients (six men, two women; median age, 38 years) fulfilled the inclusion criteria. The bite sites included the thigh (n = 4), forearm (n = 2), abdomen (n = 1), and trunk (n = 1). Time interval between the bite and first contact with our service ranged from 15 to 216 h (median = 29 h). The main clinical manifestations included local erythematous and ischemic violaceous lesions overlying a base of indurated edema (livedoid plaque, 8), local pain (8), exanthema (6), serohemorrhagic vesicles/blisters (5), fever (5), and jaundice (1). Based on a previously established classification, the cases were classified as probable cutaneous-necrotic loxoscelism (CNL, n = 4), presumptive CNL (n = 3), and presumptive cutaneous-hemolytic loxoscelism (n = 1). Seven patients were treated with anti-arachnidic antivenom (AV; median time post-bite = 46 h). Complete lesion healing ranged from 34 to 98 days post-bite (median, 68 days; six patients). None of the patients required reconstructive plastic surgery. CONCLUSIONS: The sequential photographic documentation showed considerable variation in the process of wound healing, with complete epithelialization requiring up to 3 months after the bite.

SEVERE ACUTE TOXIC EXPOSURES IN CHILDREN AND ADOLESCENTS: CASE SERIES.

OBJECTIVE: To describe a case series of severe acute toxic exposures (SATE) in individuals <20 years old followed-up by a regional Poison Control Center (PCC). METHODS: Descriptive cross-sectional study. All patients who were <20yo and classified as score 3 (severe) and 4 (fatal) following Poisoning Severity Score were included for analysis. According to the outcome, patients were classified as PSS 3 when they developed intense clinical manifestations with risk of death or important sequelae; and as PSS 4 when death had resulted from direct cause or complication of the initial exposure. The data of patients were obtained from the Brazilian electronic database system (DATATOX). RESULTS: During the biennium 2014-2015, Campinas PCC followed up 5,095 patients <20yo, with 30 being classified as SATE (PSS=3, n=24; PSS=4, n=6). The exposures circumstances were unintentional (15); intentional (14; suicide attempt = 11; street drugs consumption = 3); and not explained (1). The exposures were significantly more frequent in adolescents >14yo (n=17; p<0.01). The involved agents were venomous animals (8; scorpions=5); medicines (8; miscellaneous=6); chemicals (6); illegal rodenticides containing acetylcholinesterase inhibitors (chumbinho, 4); drugs of abuse (3); button battery (1). Three patients evolved with sequels (esophageal stricture post-corrosive ingestion). The median length of hospital stay was 6 days (IQR: 5-12 days); 26 patients were treated in intensive care units, and 22 of them needed mechanical ventilation; 12, inotropic/vasopressors; and 3, renal replacement therapy. CONCLUSIONS: Scorpion stings and poisonings caused by medicines and chemicals were the main causes of SATE. The SATE were significantly more frequent in adolescents, due to deliberate self-poisoning.

Near-fatal poisoning after ricin injection.

OBJECTIVE: To report a near-fatal poisoning after intentional injection of ricin from a castor bean (Ricinus communis) extract. CASE REPORT: A 21 year-old man self-injected ∼3 mL of a castor bean extract intramuscularly and subcutaneously in the left antecubital fossa. Upon admission to our ED (1 h post-exposure; day 1, D1) he was awake and alert, but complained of mild local pain and showed slight local edema and erythema. He evolved to refractory shock (∼24 h post-exposure) that required the administration of a large volume of fluids and high doses of norepinephrine and vasopressin, mainly from D2 to D4. During this period, he developed clinical and laboratory features compatible with systemic inflammatory response syndrome, multiple organ dysfunction, capillary leak syndrome, rhabdomyolysis, necrotizing fasciitis and possible compartment syndrome. The patient underwent forearm fasciotomy on D4 and there was progressive improvement of the hemodynamic status from D7 onwards. Wound management involved several debridements, broad-spectrum antibiotics and two skin grafts. Major laboratory findings within 12 days post-exposure revealed hypoalbuminemia, proteinuria, thrombocytopenia, leukocytosis and increases in cytokines (IL-6, IL-10 and TNF-α), troponin and creatine kinase. Ricin A-chain (ELISA) was detected in serum up to D3 (peak at 24 h post-exposure), with ∼79% being excreted in the urine within 64 h post-exposure. Ricinine was detected in serum and urine by LC-MS up to D5. A ricin A-chain concentration of 246 µg/mL was found in the seed extract, corresponding to the injection of ∼738 µg of ricin A-chain (∼10.5 µg/kg). The patient was discharged on D71, with limited range of motion and function of the left forearm and hand. CONCLUSION: Ricin injection resulted in a near-fatal poisoning that evolved with septic shock-like syndrome, multiple organ dysfunction and necrotizing fasciitis, all of which were successfully treated with supportive care.

Consecutive envenomation of two men bitten by the same coral snake (Micrurus corallinus).

Objective: To report two patients who developed systemic neurotoxicity after consecutive bites by the same coral snake.Case report: Two previously healthy men (32-year-old and 34-year-old) found a coral snake in a woodpile while collecting wood for a barbecue. During the barbecue, both men became drunk and "played" with the snake, believing that they were handling a false coral snake, and were bitten within a few minutes of each other. Both patients were admitted to a referral tertiary care hospital (175 km from where the bites occurred) 16 hours and 19 hours postbite; both showed similar features of envenomation: palpebral ptosis, muscle weakness, dysphagia, and generalized myalgia. No fang marks or local pain were detected in either case. The patients were successfully treated with Brazilian coral snake antivenom (Fab´2) and discharged one-day postadmission, with improvement of myasthenia, but still showing palpebral ptosis. The offending snake was identified as a 42-cm-long Micrurus corallinus. During follow-up, both patients reported a transitory loss of taste that lasted approximately 3-4 weeks postbite.Conclusion: Consecutive bites by the same coral snake may cause systemic neurotoxicity (acute myasthenia) in more than one person, as well as transitory loss of taste, an underreported complication of snakebites.

Thrombotic microangiopathy following Bothrops jararaca snakebite: case report.

CONTEXT: Thrombotic microangiopathy (TMA) is an uncommon and severe complication of snakebites, and is similar, in general, to hemolytic-uremic syndrome (HUS). We describe a case of TMA following envenomation by Bothrops jararaca. CASE DETAILS: A 56-y-old-woman with controlled hypertension was transferred from a primary hospital to our ER ∼7 h after being bitten by B. jararaca in the distal left leg. She developed edema extending from the bite site to the proximal thigh, associated with intense radiating local pain, local paresthesia and ecchymosis at the bite site. Laboratory features upon admission revealed coagulopathy (20 min whole blood clotting time - WBCT20 > 20 min), thrombocytopenia (76,000 platelets/mm3) and slight increase in serum creatinine (1.58 mg/dL; RV < 1.2 mg/dL). Upon admission, the patient was treated with bothropic antivenom and fluids replacement. During evolution, her thrombocytopenia and anemia worsened, with blood films showing fragmented red cells, haptoglobin consumption, increase in serum lactate dehydrogenase, and progressive increase of serum creatinine (KDIGO stage = 3). No RBC transfusion, renal replacement therapy or plasmapheresis was done. The patient showed progressive improvement from day nine (D9) onwards and was discharged on D20; there was complete recovery of hemoglobin levels at follow-up (D50). ADAMTS-13 activity, assayed 10 months post-bite, was within reference values. DISCUSSION: TMA following snakebite has been reported mainly in India, Sri Lanka and Australia, with several patients needing renal replacement therapy. Although controversial, plasmapheresis has also been used in some cases. Our patient developed microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury, a triad of features compatible with TMA similar to HUS. Despite the severity, the outcome following conservative treatment was good, with complete recovery.

Management of severe pain after dermal contact with caterpillars (erucism): a prospective case series.

CONTEXT: Erucism, envenomation caused by dermal contact with larval forms of moths, may result in intense local pain, mainly after contact with puss caterpillars (family Megalopygidae). OBJECTIVE: To evaluate the response to different treatments for controlling severe pain in a case series of erucism in Campinas, southeastern Brazil. PATIENTS AND METHODS: Prospective cohort study. A Numeric Pain Rating Scale (NPRS 0-10) was used to assess pain intensity in the Emergency Department (ED). Pain was considered as severe upon ED admission (T0) when the NPRS was ≥8. INCLUSION CRITERIA: age ≥8 years old, severe pain at T0, with continuous assessment of pain intensity in all patients using the NPRS during the ED stay (T5, T15, T30, T60 min and at discharge). RESULTS: Fifty-five patients fulfilled the inclusion criteria and were divided into three groups according to the initial treatment at T0: local anesthesia alone with 2% lidocaine (group 1, n = 15), local anesthesia and analgesics (group 2, n = 26) and analgesics without local anesthesia (group 3, n = 14). Most patients were admitted within 2 h after dermal contact with the stinging bristles of caterpillars (median =90 min, IQR: 40-125 min). In 22 cases (40%), the caterpillar was brought for identification (Podalia spp., n = 18; Megalopyge spp., n = 4). There was a significant decrease in pain from T5 onwards with all of the treatments. When the short-term response (T5 and T15) was considered, analgesia was more effective in groups 1 and 2 compared to group 3 (p < .01). Additional analgesia (from T5 until discharge) was frequently required (n = 25/55), mainly in group 1 (n = 11/15). The median length of stay in the ED was 120 min (IQR: 80-173 min). CONCLUSIONS: The association of local anesthesia with analgesics was apparently a good combination for the rapid management of severe pain in the ED.

Infective endocarditis due to Haemophilus aphrophilus: a case report.

OBJECTIVE: To report the case of a child with infective endocarditis caused by Haemophilus aphrophilus. DESCRIPTION: Boy with 20 days of fever and chills. On admission, he was febrile, pale and with no signs of hemodynamic instability; on cardiac auscultation, a mitral-related holosystolic murmur was observed. Laboratory examination identified anemia (hemoglobin = 9.14 g/dL), total leukocytes of 11,920 mm3, platelets of 250,000 mm3, elevated sedimentation velocity of red cells and elevated C-reactive protein. The echocardiogram revealed image on mitral valve, resembling vegetation. Considering endocarditis, antibiotic therapy was started with crystalline penicillin (200,000 UI/kg/day) in association with gentamicin (4 mg/kg/day). On the third day of treatment, Haemophilus aphrophilus was identified in the blood cultures and the antibiotic scheme was replaced with ceftriaxone (100 mg/kg/day). On the 20th day of evolution, the patient was pale but with no fever or other complaints. Examinations showed hemoglobin = 7.0 g/dL, leukocytes = 2,190 mm3, platelets = 98,000 mm3, international normalized ratio = 1.95 and R = 1.89. Considering the hypothesis of adverse reaction to ceftriaxone, a 6-week replacement treatment with ciprofloxacin (20 mg/kg/day) was started. Examination results normalized after 72 hours of the replacement therapy. During ambulatory follow-up, patient presented with severe mitral regurgitation, undergoing a valve replacement with a metallic prosthetic valve 9 months after acute event. Patient has done well throughout the 3-year ambulatory follow-up. COMMENTS: Identification of agents of the HACEK group (Haemophilus ssp, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae) in children with infective endocarditis is rare. This case report, with no HACEK agent-related risk factors, reinforces the need for identification of the etiological agent of endocarditis to ensure adequate treatment.

Self-medication in children and adolescents.

OBJECTIVE: To determine the prevalence of self-medication in children and adolescents in the municipalities of Limeira and Piracicaba, state of São Paulo, and to correlate results with sociodemographic indicators and with the use of health care services (public or private). METHODS: Descriptive population-based study of a simple random sample from the two municipalities, comprised of 772 inhabitants from 85 urban census sectors selected through cluster sampling. INCLUSION CRITERIA: age < or = 18 years; interview with one parent/tutor; consumption of at least one drug in the previous 15 days. Subjects were divided into two study groups according to their pattern of drug use: self-medication (lay advice) and medical prescription. Linear association tests, descriptive analysis of variables and multiple logistic regression tests were carried out to analyze data. RESULTS: The prevalence of self-medication was 56.6%. Mothers (51%) and drugstore employees (20.1%) were most frequently responsible for self-medication. The main groups of self-prescribed drugs were: analgesic/antipyretic and non-hormonal anti-inflammatory drugs (52.9%); drugs acting on the respiratory tract (15.4%) and gastrointestinal drugs (9.6%); and systemic antibiotics (8.6%). The situation that most commonly motivated self-medication were respiratory diseases (17.2%), fever (15%), and headache (14%). Subjects in the age group of 7-18 years (odds ratio = 2.81) and public health care users (odds ratio = 1.52) showed increased risk for self-medication. CONCLUSIONS: The prevalence of self-medication in children and adolescents was high, which reinforces the need for public health interventions aiming at preventing this practice.

Temporal evolution of dermonecrosis in loxoscelism assessed by photodocumentation

ABSTRACT Background: Although loxoscelism (bites by brown spiders of the genus Loxosceles) frequently results in dermonecrosis, no previous clinical reports have provided detailed temporal photodocumentation of the evolution of dermonecrotic lesions in a case series. Methods This was a retrospective cohort study involving a case series of loxoscelism. Only cases of dermonecrosis with photodocumentation of lesion evolution (from admission until complete or almost complete healing) were included. Results: Eight patients (six men, two women; median age, 38 years) fulfilled the inclusion criteria. The bite sites included the thigh (n = 4), forearm (n = 2), abdomen (n = 1), and trunk (n = 1). Time interval between the bite and first contact with our service ranged from 15 to 216 h (median = 29 h). The main clinical manifestations included local erythematous and ischemic violaceous lesions overlying a base of indurated edema (livedoid plaque, 8), local pain (8), exanthema (6), serohemorrhagic vesicles/blisters (5), fever (5), and jaundice (1). Based on a previously established classification, the cases were classified as probable cutaneous-necrotic loxoscelism (CNL, n = 4), presumptive CNL (n = 3), and presumptive cutaneous-hemolytic loxoscelism (n = 1). Seven patients were treated with anti-arachnidic antivenom (AV; median time post-bite = 46 h). Complete lesion healing ranged from 34 to 98 days post-bite (median, 68 days; six patients). None of the patients required reconstructive plastic surgery. Conclusions The sequential photographic documentation showed considerable variation in the process of wound healing, with complete epithelialization requiring up to 3 months after the bite.

TOXIC EXPOSURES IN CHILDREN INVOLVING LEGALLY AND ILLEGALLY COMMERCIALIZED HOUSEHOLD SANITIZERS. / EXPOSIÇÕES TÓXICAS EM CRIANÇAS A SANEANTES DE USO DOMICILIAR DE VENDA LEGAL E CLANDESTINA.

OBJECTIVES: To analyze and to compare clinical repercussions of accidents involving legally and illegally commercialized household sanitizers in children under 7 years of age. METHODS: A descriptive cross-sectional design was used to collect data from electronic database of a regional Poison Control Center during one year. Data were analyzed by means of descriptive non-parametric statistics and association tests. Results: The sample had 737 reported cases. Most of the accidents occurred with children under 3 years of age (median: 1 year of age; interquartile interval: 1-3 years of age), at home (92.9%), by ingestion (97.2%). Products involved were cleaning products with low toxicity and no caustic effects (38.9%); caustics (24.1%); hydrocarbons (19.3%); pesticides/rodenticides (16.6%), and other products (1.1%). Seventy accidents were due to exposures to illegal products, mainly caustics (n=47) and rodenticides (n=15). Among the 337 children presenting post-exposure clinical manifestations, the most frequent were vomiting (n=125), oral burns (n=74), cough (n=35), drooling (n=26), and abdominal pain (n=25). Clinical manifestations were significantly more frequent after illegal products exposure (55/70 versus 282/667, p<0.01). Nineteen children had to be hospitalized (caustics, n=17; illegal products, n=12; median time of hospitalization: 2 days), 22 were submitted to esophagogastroduodenoscopy (sodium hydroxide, n=14; illegal products, n=14); and 12 cases had endoscopic alterations (severe in 2). No deaths occurred. CONCLUSION: Toxic exposures owing to illegal household sanitizer products are associated with greater morbidity when compared with legal ones.

OBJETIVOS: Analisar e comparar as repercussões clínicas dos acidentes com saneantes de uso domiciliar de origem legal e ilegal (clandestina) em crianças menores de 7 anos. MÉTODOS: Estudo descritivo de corte transversal, com dados obtidos dos prontuários eletrônicos do Centro de Informações e Assistência Toxicológica de referência regional, no período de um ano completo. Foram realizadas análises estatísticas descritivas não paramétricas e de testes de associação. Resultados: A amostra foi constituída de 737 casos. A maioria das exposições ocorreu em crianças menores de 3 anos (mediana: 1 ano, intervalo interquartil: 1-3 anos) na residência habitual (92,9%) e por ingestão (97,2%). Os produtos envolvidos foram saneantes de baixa toxicidade sem efeito cáustico (38,9%), com efeito cáustico (24,1%), hidrocarbonetos (19,3%), inseticidas/raticidas (16,6%), e outros produtos (1,1%). Setenta casos decorreram de exposições a produtos clandestinos, principalmente cáusticos (n=47) e raticidas (n=15). Entre as 337 crianças que apresentaram manifestações clínicas pós-exposição, as ocorrências mais frequentes foram vômitos (n=125), queimaduras orais (n=74), tosse (n=35), salivação (n=26) e dor abdominal (n=25), significativamente mais comum com produtos clandestinos (55/70 versus 282/667; p<0,01). Dezenove crianças foram hospitalizadas (cáusticos, n=17; produtos clandestinos, n=12; mediana do tempo de internação: 2 dias), e 22 foram submetidas à endoscopia digestiva alta (hidróxido de sódio, n=14; produtos clandestinos, n=14), com alterações em 12 casos (grave=2). Não houve óbitos. CONCLUSÕES: Exposições tóxicas a saneantes de uso domiciliar de origem clandestina estão associadas com maior morbidade quando comparadas aos de venda autorizada.

Antidote availability in the municipality of Campinas, São Paulo, Brazil.

CONTEXT AND OBJECTIVE:: The lack of availability of antidotes in emergency services is a worldwide concern. The aim of the present study was to evaluate the availability of antidotes used for treating poisoning in Campinas (SP). DESIGN AND SETTING:: This was a cross-sectional study of emergency services in Campinas, conducted in 2010-2012. METHODS:: The availability, amount in stock, place of storage and access time for 26 antidotal treatments was investigated. In the hospitals, the availability of at least one complete treatment for a 70 kg adult over the first 24 hours of admission was evaluated based on stock and access recommendations contained in two international guidelines. RESULTS:: 14 out of 17 functioning emergency services participated in the study, comprising pre-hospital services such as the public emergency ambulance service (SAMU; n = 1) and public emergency rooms for admissions lasting ≤ 24 hours (UPAs; n = 3), and 10 hospitals with emergency services. Six antidotes (atropine, sodium bicarbonate, diazepam, Phytomenadione, flumazenil and calcium gluconate) were stocked in all the services, followed by 13 units that also stocked activated charcoal, naloxone and diphenhydramine or biperiden. No service stocked all of the recommended antidotes; only the regional Poison Control Center had stocks close to recommended (22/26 antidotal treatments). The 10 hospitals had almost half of the antidotes for starting treatments, but only one quarter of the antidotes was present with stocks sufficient for providing treatment for 24 hours. CONCLUSION:: The stock of antidotes for attending poisoning emergencies in the municipality of Campinas is incomplete and needs to be improved.

Suicide attempt with acetonitrile ingestion in a nursing mother.

CONTEXT: Acetonitrile (ACN) is a solvent rapidly absorbed through lungs and intestinal tract, and is slowly metabolized to cyanide (CN) by enzymatic processes mediated by CYP2E1. OBJECTIVE: To describe the clinical and laboratory evolution, ACN elimination half-life, and its presence in breast milk in a nursing mother who attempted suicide. CASE DETAILS: A 25-year-old 2-month nursing mother ingested an estimated dose of 2.1 g/kg of ACN. Blood and urine samples were collected 24 h later for ACN, CN and thiocyanate analysis, and 12.5 g sodium thiosulfate i.v. in 1-h infusion was started and repeated every 24 h for 4 days. ACN results showed 200 mg/L in blood and 235 mg/L in urine. ACN analysis in the breast milk at Day 6 showed level of 21 mg/L compared to 27 mg/L in blood collected at the same time, suggesting a possible relationship of 1.3:1.0 ratio. An elimination half-life of 40.4 h was calculated, compared to 32 and 36 h showed in other studies. DISCUSSION: The clinical management must involve the use of CN antidotes for more than 24 h depending on the symptoms and blood levels of ACN. Furthermore, our data showed the possible existence of a close relationship between plasma and breast milk levels.

Bites by coral snakes (Micrurus spp.) in Campinas, State of São Paulo, Southeastern Brazil.

Coral snakes (Micrurus spp.) are the main representatives of the Elapidae in South America. However, bites by these snakes are uncommon. We retrospectively reviewed the data from 11 individuals bitten by coral snakes over a 20-year period; four were confirmed (snake brought for identification) and seven were highly suspected (neuromuscular manifestations) cases of elapid envenoming. The cases were classified as dry-bite (n = 1, caused by M. lemniscatus; did not receive antivenom), mild (n = 2, local manifestations with no acute myasthenic syndrome; M. frontalis and Micrurus spp.), moderate (n = 5, mild myasthenia) or severe (n = 3, important myasthenia; one of them caused by M. frontalis). The main clinical features upon admission were paresthesia (local, n = 9; generalized, n = 2), local pain (n = 8), palpebral ptosis (n = 8), weakness (n = 4) and inability to stand up (n = 3). No patient developed respiratory failure. Antivenom was used in ten cases, with mild early reactions occurring in three. An anticholinesterase drug was administered in the three severe cases, with a good response in two. No deaths were observed. Despite the high toxicity of coral snake venoms, the prognosis following envenoming is good. In serious bites by M. frontalis or M. lemniscatus, the venom of which acts postsynaptically, anticholinesterases may be useful as an ancillary measure if antivenom is unavailable, if there is a delay in obtaining a sufficient amount, or in those patients given the highest recommended doses of antivenom without improvement of the paralysis or with delayed recovery.

Fatal ischemic stroke following Tityus serrulatus scorpion sting in a patient with essential thrombocythemia.

CONTEXT: Stroke following scorpion stings is rare. We report a fatal envenomation involving multiple, extensive brain infarcts in a patient with a previous diagnosis of essential thrombocythemia (ET) who was stung by Tityus serrulatus (T. serrulatus). CASE DETAILS: A 44-year-old woman with a diagnosis of low-risk ET (platelets <1,000,000/mm3, age <60 years and no history of thrombosis; positive JAK2V617F mutation) was admitted to a local ED 1 h after being stung by T. serrulatus on the left foot. She developed signs of severe envenomation, including several episodes of profuse vomiting, pallor and confusion soon after the sting, followed by shock (BP: 90/60 to 60/40 mmHg) and was treated with scorpion antivenom, vasopressors and mechanical ventilation. A brain computed tomography (CT) scan (54-h poststing) revealed diffuse bilateral cerebellar hypodensity, with partial involvement of both occipital lobes and thalamus, obstructive hydrocephaly with signs of cerebrospinal fluid extravasation, and ascending transtentorial herniation, suggestive of bilateral ischemia involving the posterior cerebral circulation. External ventricular drainage resulted in no improvement and brain death was confirmed on day 10. DISCUSSION: Several mechanisms have been proposed to explain stroke following scorpion stings, such as sympathetic stimulation, myocardial dysfunction, hypotension/shock, arrhythmias and coagulopathy. Ischemic stroke is one of the most serious complications of ET. The risk factors for thrombotic/ischemic events in patients with ET include age (≥60 years) and previous vascular events. Severe scorpion envenomation resulting in myocardial dysfunction and systemic inflammatory response syndrome may increase the overall risk of arterial thrombosis in this patient.

Coral snake bites (Micrurus spp.) in Brazil: a review of literature reports.

CONTEXT: In the Americas, the main representatives of the family Elapidae are coral snakes of the genus Micrurus, of which 33 species are in Brazil. They are the smallest cause of venomous snakebite in Brazil. We analyzed literature reports of coral snake bites in Brazil from 1867 to 2014, and provide a brief review of case series and reports of coral snake bites in the Americas in general. METHODS: Only reports with clinical descriptions of envenomation were included. The variables recorded included identification of the offending snake, patient's age, sex, bite site, clinical manifestations, treatment, including antivenom and anticholinesterase drugs, and general evolution of the cases. 30 published reports describing bites caused by Micrurus spp. in Brazil were identified and involved 194 distinct cases. Since no information on the clinical manifestations was available in 44 cases, the analysis was restricted to 25 reports (150 cases). RESULTS: Most patients were from southern (61.3%; primarily Santa Catarina state, 60%) and southeastern (20%) Brazil and were male (70.7%), with a median age of 27 years (interquartile interval = 18 to 40 years). The offending snakes were described in 59 cases (M. corallinus 36, M. frontalis 12, M. lemniscatus 5, M. hemprichi 2, M. filiformis 1, M. ibiboboca 1, M. spixii 1 and M. surinamensis 1); in 22 cases only the genus (Micrurus spp.) was reported. Of the 143 cases in which the bite site was recorded, most involved the hands (46.2%) and feet (26.6%). The main clinical features were local numbness/paresthesia (52.7%), local pain (48%), palpebral ptosis (33.3%), dizziness (26.7%), blurred vision (20.7%), weakness (20%), slight local edema (16%), erythema (16%), dysphagia (14.7%), dyspnea (11.3%), inability to walk (10.7%), myalgia (9.3%), salivation (8%) and respiratory failure (4.3%). Fang marks were described in 47.3% of cases and 14% of bites were classified as asymptomatic. A slight increase in total blood creatine kinase was reported in 3 children, suggesting mild myotoxicity. Therapeutic procedures included coral snake antivenom (77.3%), anticholinesterase drugs (6%), and mechanical ventilation (3.3%). Two patients reported in 1933 developed paralysis/respiratory failure and died 6 h and 17 h post-bite. Four more deaths probably caused by coral snakes were reported (2 in 1867, 1 in 1959, 1 in 1962), but no clinical information was available. DISCUSSION: Neuromuscular blockade was the hallmark of systemic envenomation by Micrurus spp., with signs of myasthenia such as weakness and ptosis that may evolve to paralysis and respiratory failure. Local features, mainly numbness/paresthesia and pain, were frequently reported, with the pain being intense in some cases. Although myotoxicity has been detected in experimental studies with Micrurus spp. venoms, few human reports described laboratory findings compatible with myotoxicity. CONCLUSION: Most coral snake bites reported in Brazil were caused by M. corallinus and M. frontalis, with several patients showing signs of acute myasthenia. Serious complications such as paralysis with respiratory failure were observed but comparatively rare. The deaths occurred where respiratory support (mechanical ventilation) was unavailable when needed.

Severe acute toxic exposures in children and adolescents: case series / Exposições tóxicas agudas graves em crianças e adolescentes: série de casos

ABSTRACT Objective: To describe a case series of severe acute toxic exposures (SATE) in individuals <20 years old followed-up by a regional Poison Control Center (PCC). Methods: Descriptive cross-sectional study. All patients who were <20yo and classified as score 3 (severe) and 4 (fatal) following Poisoning Severity Score were included for analysis. According to the outcome, patients were classified as PSS 3 when they developed intense clinical manifestations with risk of death or important sequelae; and as PSS 4 when death had resulted from direct cause or complication of the initial exposure. The data of patients were obtained from the Brazilian electronic database system (DATATOX). Results: During the biennium 2014-2015, Campinas PCC followed up 5,095 patients <20yo, with 30 being classified as SATE (PSS=3, n=24; PSS=4, n=6). The exposures circumstances were unintentional (15); intentional (14; suicide attempt = 11; street drugs consumption = 3); and not explained (1). The exposures were significantly more frequent in adolescents >14yo (n=17; p<0.01). The involved agents were venomous animals (8; scorpions=5); medicines (8; miscellaneous=6); chemicals (6); illegal rodenticides containing acetylcholinesterase inhibitors (chumbinho, 4); drugs of abuse (3); button battery (1). Three patients evolved with sequels (esophageal stricture post-corrosive ingestion). The median length of hospital stay was 6 days (IQR: 5-12 days); 26 patients were treated in intensive care units, and 22 of them needed mechanical ventilation; 12, inotropic/vasopressors; and 3, renal replacement therapy. Conclusions: Scorpion stings and poisonings caused by medicines and chemicals were the main causes of SATE. The SATE were significantly more frequent in adolescents, due to deliberate self-poisoning.

RESUMO Objetivo: Descrever uma série de casos de exposições tóxicas agudas graves (ETAG) em pacientes <20 anos seguidos por um Centro de Informação e Assistência Toxicológica (CIATox) regional. Métodos: Estudo descritivo de corte transversal. Incluídos no estudo todos os casos classificados como escore 3 (graves) e 4 (fatais) de acordo com o escore de gravidade de intoxicações (poisoning severity score - PSS). Segundo o PSS, os casos são classificados em relação ao desfecho como escore 3 quando os pacientes desenvolveram manifestações clínicas intensas, com risco de morte ou que resultaram em sequelas importantes; e escore 4 quando a morte foi resultado de causa direta ou por complicação da exposição. Os dados analisados foram obtidos da base eletrônica brasileira do Sistema Nacional de Informações Tóxico-Farmacológicas DATATOX. Resultados: No biênio 2014-2015 o CIATox de Campinas atendeu 5.095 casos de pacientes <20 anos, dos quais 30 foram classificados como ETAG (PSS=3, n=24; PSS=4, n=6). Quanto à circunstância, 15 foram acidentais, 14 intencionais (11 por tentativas de suicídio e três por abuso de drogas) e um de causa não esclarecida, sendo significativamente mais frequentes nos adolescentes >14 anos (n=17; p<0,01). Os grupos de agentes envolvidos foram: animais peçonhentos (8; escorpiões=5); medicamentos (8; associações=6); produtos químicos de uso domiciliar/industrial (6); rodenticidas inibidores da colinesterase de uso ilegal (chumbinho=4); drogas de abuso (3); e bateria no formato de disco (1). Três pacientes evoluíram com sequelas (estenose esofágica pós-ingestão de corrosivos). O tempo mediano de internação foi de seis dias (mediana, quartis e intervalo interquartil=5-12 dias), sendo 26 pacientes admitidos em unidades de cuidados intensivos, dos quais 22 necessitaram de ventilação mecânica, 12 de inotrópicos/vasopressores e três de terapia de substituição renal. Conclusões: Escorpionismo e intoxicações por medicamentos e por produtos químicos de uso domiciliar/industrial foram as principais causas de ETAG, sendo elas significativamente mais frequentes em adolescentes, principalmente por tentativas de suicídio.

[Acute toxic exposure in children: an overview]. / Exposições tóxicas agudas em crianças: um panorama.

OBJECTIVE: To review the literature on acute toxic exposure in children, excluding envenomations. SOURCES OF DATA: MEDLINE review (emphasis on the past decade), including the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists position statements and position papers (peer-reviewed information based on scientific evidence and broad consensus) on gastrointestinal decontamination, multiple-dose activated charcoal and urine alkalinization. SUMMARY OF THE FINDINGS: Acute toxic exposure in children is a common event, mainly in children under six years of age. Death is rare. Although widely employed, there is no evidence that gastrointestinal decontamination and multiple-dose activated charcoal improve the outcome of poisoned patients. Very few efficient antidotes are used on a consistent basis, and some of them are very expensive and not available in Brazil. CONCLUSIONS: Ipecac syrup and cathartics should not be administered on a routine basis in acute toxic exposures in outpatient treatment. Excluding the contraindications, single-dose activated charcoal and gastric lavage may be considered within one hour of ingestion if a patient ingested a potentially toxic amount or a potentially lethal amount, respectively. Whole bowel irrigation, multiple-dose activated charcoal and urine alkalinization may be considered in a few situations. Fomepizole and octreotide are safe and efficient antidotes, which can be used in the treatment of alcohol (methanol and ethylene glycol) and sulfonylureas poisoning, respectively.

Dapsone hypersensitivity syndrome in an adolescent during treatment during of leprosy.

A 12 y old girl was admitted 24 days after start a WHO multidrug therapy scheme for multibacillary leprosy (dapsone, clofazimine and rifampicin) with intense jaundice, generalized lymphadenopathy, hepatoesplenomegaly, oral erosions, conjunctivitis, morbiliform rash and edema of face, ankles and hands. The main laboratory data on admission included: hemoglobin, 8.4 g/dL; WBC, 15,710 cells/mm3; platelet count, 100,000 cells/mm3; INR = 1.49; increased serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, direct and indirect bilirubin. Following, the clinical conditions had deteriorated, developing exfoliative dermatitis, shock, generalized edema, acute renal and hepatic failure, pancytopenia, intestinal bleeding, pneumonia, urinary tract infection and bacteremia, needing adrenergic drugs, replacement of fluids and blood product components, and antibiotics. Ten days after admission she started to improve, and was discharged to home at day 39th, after start new supervised treatment for leprosy with clofazimine and rifampicin, without adverse effects. This presentation fulfils the criteria for the diagnosis of dapsone hypersensitivity syndrome (fever, generalized lymphadenopathy, exfoliative rash, anemia and liver involvement with mixed hepatocellular and cholestatic features). Physicians, mainly in geographical areas with high prevalence rates of leprosy, should be aware to this severe, and probably not so rare, hypersensitivity reaction to dapsone.