A retrospective review of rattlesnake bites in 100 children

Transcription

1 2015 EDIZIONI MINERVA MEDICA Online version at Approximately 700 species and subspecies of reptiles have been identified in Mexico. Of these, 120 are poisonous. Geographically, rattlesnakes (Crotalus) are prevalent in an extensive area in northern Mexico. In the state of Sonora, which borders Arizona (USA), 16 species and subspecies of the genus Crotalus have been identified. Crotalus atrox (western diamondback rattlesnake) and Crotalus cerastes (sidewinder rattlesnake) cause most of the snakebites in Sonora. There were less snake bites by agkinstrodon bilineatus at the border COPYRIGHT 2017 EDIZIONI MINERVA MEDICA ORIGINAL ARTICLE A retrospective review of rattlesnake bites in 100 children Norberto 1 *, Norberto GÓMEZ-RIVERA 2 Minerva Pediatrica 2017 April;69(2):121-8 DOI: /S Department of Medicine and Health Sciences, University of Sonora, Children s Hospital of the State of Sonora (HIES), Hermosillo, Sonora, Mexico; 2 Emergency Service, Children s Hospital of the State of Sonora (HIES), Hermosillo, Sonora, Mexico *Corresponding author: Norberto Sotelo-Cruz, Department of Medicine and Health Sciences, University of Sonora, Av. Colosio S/N entre Reforma y Francisco Q. Salazar, Col. Centro, Hermosillo, Sonora, México. nsotelo51@gmail.com ABSTRACT BACKGROUND: A retrospective review of clinical features and treatment of children hospitalized for rattlesnake bite. METHODS: One hundred clinical records were reviewed. Variables included: age, gender, season of the year, signs, symptoms, poisoning grade, complications, treatment and sequelae. RESULTS: Fifty-nine percent were males and 37% were less than 5 years of age; 87% occurred in rural areas; 63% of the snakebites occurred during the summer, of them, 39% occurred within the perimeter of the domicile and 8% within the home. Sixty-seven percent of children bitten by snakes reached the second degree of envenomation. During the first period ( ), treatment for intoxication included treatment with polyvalent equine anti-snake venom serum. During the second period ( , a polyvalent polyclonal horse anti-snake venom F(Ab) was used. The second period hospitalization time was reduced to 3.9 days (P<0.0001). Hematological complications dominated during the first period (P=0.093) with wound infections occurring in 26% of the cases, neurological symptoms in 24 %, fasciotomy in 6% and mortality in 1%. The second degree poisoning was more frequent and was more severe in 7% of the patients. It was determined that the best treatment for snakebite was F(Ab ) 2 therapy. Mortality occurred in 1% of the cases. CONCLUSIONS: Rattlesnake (Crotalus sp.) bite, in Mexico is less frequent as compared to other crotalidae species. The hematological complications are more frequent. We did not observe any recurrent phenomenons. (Cite this article as: Sotelo-Cruz N, Gómez-Rivera N. A retrospective review of rattlesnake bites in 100 children. Minerva Pediatr 2017;69: DOI: /S ) Key words: Crotalus - Snake bites, complications - Child. of Sonora and Sinaloa. In Oaxaca, Guerrero, Veracruz, Tamaulipas are in first place for snake bites. Of these, 68% were of the subfamily Crotalinae genus Botrhops and only 9.9% by agkinstrodon. 1-4 Most snakebites occurred during the spring and summer months. Generally the bites that occurred in rural areas were within the perimeter of the home, and sometimes even within the home itself. Accidents also occur in urban areas but to a lower extent In Mexico, from , snakebites oc- Vol No. 2 Minerva Pediatrica 121

2 curred in 18,842 individuals. Of these, 2912 (15.4%) had fatal outcomes. From January 2009 through May 2014, snakebites were reported in 20,281 cases. The mortality rate decreased during the time period from 5 to 2 per 100,000 persons. 1-4 Worldwide, 5400,000 snakebites were reported yearly. Of these, 2500,000 were from poisonous snakes. Mortality due to these bites ranged from 40,000 to 150, Snake venom is a very complex compound, containing as many as 30 metalloproteinases. These metalloproteinases cause bleeding. The venom also contains low-molecular-weight (LMW) polypeptides which can lead to cardio and neurotoxic complications. Other components within the venom are responsible for edema, histological damage, endothelial lesions, hematological disorders, kidney dysfunction, and neurological effects. 8, Gross clinical symptoms include localized pain, edema, ecchymotic lesions, local necrosis, phlyctenas, somnolence, paresthesias, vomiting and, in severe cases, hypotonia, oliguria, stupor, coma, and shock. To facilitate the identification of snakebite, diverse classifications have been described. We employ the classification of Christopher and Rodning. 11, The basic and most important treatment in Mexico is the antivenom. At present, the commercial anti-venom available in Mexico consists of a horse F(Ab ) 2 preparation, also known as fabotherapy. 11, 19, 22, 23 This therapy is recommended at multiple doses according to the degree of the envenomation and poisoning is controlled, reducing complications and hospitalization time. 9-11, The objective of this study was the follow-up of 100 children bitten by rattlesnakes. These were the children that received treatment at a pediatric hospital in northwestern Mexico during the past 37 years. Materials and methods Retrospective and descriptive review of the clinical records of patients treated for snakebite at the Children s Hospital of the State of Sonora (Hospital Infantil del Estado de So- nora, HIES) in Mexico from were performed. Patients who were sent to other hospitals or who were bitten by other varieties of snakes were excluded from the study. The variables included gender, age, place of residence, time of incident, time from incident to hospital care, and season of the year. In addition, signs and symptoms, laboratory tests, length of hospitalization treatment, and sequelae were reviewed. The most relevant data was reported in descriptive statistics and in non-parametric tests such as those described by Welch, Barttlet, and Levene, Wilcoxon, the Pearson χ 2 test. The Spearman Rank Correlation Determinant Coefficient Test was utilized for comparison of complications and length of hospital stay of the two periods from (group I) and (group II). Statistical analysis We used the JMP/SAS version 10.0 statistical software package. 25 Results Demographics Of the 100 patients, 59 were male and 41 were female. Most of the pediatric patients were from the rural area (87%). Snakebites occurred in 13% in the open countryside; in 39% of the cases, the snakebites occurred within the patio of the children s home. Other data as day hour, season of the year, ages and lesion site are presented in Tables I, II. The following occurrences drew our attention: an adolescent hit a snake s head with a hatchet. The fangs entered the adolescent s right hand and injected venom, the venom traversed the cephalic vein and through the upper right limb. Three cases occurred within the city limits. One occurred within the perimeter of the suburban home, another in a school sports field while the child was seated on the grass and the third one when the child was riding in the back of a pick-up loaded with firewood. 122 Minerva Pediatrica april 2017

3 First aid Elapsed time from the moment of the snakebite incidence to hospital treatment was <1 hour in 25% of the children and 1 to 3 hours in 38% of the cases. Twenty percent of the patients arrived at the hospital between 3 and 24 hours after the bite. Eight percent arrived after 24 hours and 2% arrived after 48 hours. First aid was administered at the site of the snakebite. This was prior to hospital admittance and application of the anti-venom by physicians. In 40% of the patients, 1 to 2 vials of anti-venom were administered and 22% of the patients received 3 to 8 vials. Ten percent of the patients presented with an incision on the bite site. In 7% of the cases, incision and oral suction was performed. This oral suction employed a double-chamber vacuum/suction apparatus. Ice was applied to 2% to the localized area and also multiple small incisions were made within the thigh and leg. One child was given garlic and milk (1%) to drink. The predominant signs and symptoms were pain, edema, functional disability, ecchymosis, somnolence, paresthesia, and bleeding at the lesion site. For the degree of envenomation, the Christopher-Rodning Classification 17 was considered (Tables III, IV). Laboratory testing Laboratory tests reported prolonged prothrombin time in 69% of the patients and Table I. Demographics. N.=100. Location % Time of day % Season % Rural area 87 During the morning 16 Spring 13 Open country side 13 2 to 8 pm 70 Summer 63 Children s home patio 39 After 9 pm 13 Autumn 23 Into the home 8 Winter 1 Agriculture field 3 Swimming in a river 1 City suburban area 3 Table II. Age and lesions location. Age (in years) % Lesions location % 1 to 2 years 10 Upper limbs 25 3 to 5 years 27 Legs and feet 74 6 to 10 years 24 Gluteous 1 11 to Table III. Signs and symptoms in 100 children with rattlesnake bite. Signs and symptoms Number of cases (100) % Pain Edema Functional disability Lesion site bleeding, ecchymoses, phlyctenule Somnolence, paresthesia Vomiting Local necrosis Loss of consciousness 2 2 Epistaxis 3 3 Hematuria 2 2 State of shock 3 3 Table IV. Degree of envenomation (Christopher- Rodning Classification). Degree % 0 Signs of bite without envenomation 3 I Slight envenomation, edema <10 c 18 II Moderate envenomation, greater pain, 60 edema >10 cm III Severe envenomation, abdominal pain, nausea, 7 petechiae, necrosis, paresthesias, bullae, oliguria IV Serious envenomation, renal insufficiency, 3 disseminating intravascular coagulation (DIC), respiratory failure, multiple organ failure Not described 9 10% of the patients had partial thromboplastin time (PTT) alteration. Hemoglobin was <10 gr/dl in 36% of the cases. Of these, only 5% had reticulocytes of >5%. Low fibrinogen was observed in 25% of the children, platelets <100,000 mm 3 in 7%, glucose >110 mg/dl in 12%, and altered urea, creatinine, U/P relation tests of urea, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in 8%, and creatine phosphokinase in 17 cases was > U/L, amylase was >1690 U/L, and calcium was <8 mg/dl in one case (1%). Vol No. 2 Minerva Pediatrica 123

4 Bacterial culture of the wound area revealed Staphylococcus aureus in 33%, followed by Klebsiella spp. in 8% of the patients. Treatment Supporting therapy consisted of the application of parenteral solutions such as penicillin-type antibiotics, aminoglucosides, tetanus toxoid, hyperimmune antitetanus gamma globulin, hydrocortisone, calcium gluconate and pressor amines. Forty-eight percent of the patients received analgesics. Of these patients, 2% received aspirin and 46% received acetaminophen, ketorolac, or metamizole. Assisted ventilation was performed on 2% of the patients, peritoneal dialysis on 1%, fasciotomy on 6%, and 2% did not receive any treatment. The remaining patients were observed in the emergency room for 12 hours. Complete blood analysis was performed for the emergency room patients. They also underwent tests for evaluation of bleeding. Transfusions were administered to 30% of the patients. This included cryoprecipitates, fresh plasma, fresh whole blood and platelets. Heparin was given to 7% of the patients and dipyridamol to 4%. In the first retrospective period (1977 to 1996), 32 patients were treated. Of these, 30 received anti-venom therapy; 2 of the patient did not receive any anti-venom treatment since they had dry bites. From 1977 to 1985, 11 children received diverse therapy since there was no standardized protocol for snakebite treatment at that time. Emergency physicians applied 1 and 6 vials of polyvalent anti-snake venom serum with horse-gamma globulin, which contained 2 g of protein and 129 mg of albumin in each vial. From 1986, a treatment regimen was initiated according to the degree of envenomation diagnosed. Patients with grade II or moderate poisoning were administered 4 vials of serum in physiological solution within the first hour and additional 3 to 4 vials within the next hour. For more severe envenomation (grades III and IV), 6 to 8 vials diluted in 250 ml of physiological solution were given during the first hour, 8 to 10 vials were added during the following 3 hours (up to 15 vials were recommended in total for the first 4 hours). This therapeutic regimen was maintained until , 10, 18 In 1997, we modified our treatment. We began using polyclonal anti-snake venom F(Ab ), 2 of hyperimmune immunoglobulin (IgG) obtained from horse serum to which Crotalus spp. and Bothrops spp. venom had been administered (Equine-derived fabotherapy). From 1997 to the present, this medication was employed according to the degree of poisoning. In one child, diagnosed with a dry bite, three vials were applied. The customary regimen for grade I bite determination, was up to 3 vials with direct intravenous (i.v.) application at the rate of 1 ml per minute. The following hour, 4 vials diluted in 100 ml of physiological solution were given. Assessments were made every 3 hours. Four more vials were added accordingly to the evaluation of the patient s clinical condition, hematological changes, and kidney function. After every 4-hour evaluation, additional doses would be given if necessary. For grade II poisoning, treatment was initiated with 5 vials intravenously and subsequently 10 vials during the following hour. Utilization assessments were made after using 6-8 vials. This would depend on the patient s response to treatment. For grade III poisoning, 5 vials were directly administered intravenously and 20 vials within the following hour. Subsequent patient evaluation was made to determine if the application of 6-8 vials of anti-venom were needed. Following assessments were made every four hours to determine if 4-5 additional vials of anti-venom were needed. For grade IV poisoning, 25 vials were administered intravenously. This was followed by an additional 25 vials during the subsequent hour. Assessments of the utilization of 10 vials in 3 hours according to the patient s clinical state, controls and the application of 4-5 vials every 4 hours were made. 11 The maximum dose of fabotherapy administered was 69 vials with range 48 to 60 vials in patients with se- 124 Minerva Pediatrica april 2017

5 Most of the snakebites that were reported at the Children s Hospital of Sonora (69%) were a result of Crotalus atrox, Crotalus cerastes, Crotalus molossus, and Crotalus tigris bites. The first two species, Crotalus atrox and cerastes account for 60% of all snakebites. In 31% of the cases, the snake type was not identified since it occurred at night. Because of the semi-desert conditions of our population, there was no incident of Botrohtps snakebits, but only bites by the genus agkinstrodon. 3-7, 11, 23 It has been reported that these types of snakebites occur in adult males who work in agriculture, zoos, and in herpetological investivere envenomation. Among the patients treated, we did not report immediate or late allergic reactions to therapy in the 8 weeks following the patients discharge from the hospital. Hospital stay for the patients full recovery was different for children of the two care periods. The second period included 68 children ( ) whose hospital stay was shorter after receiving multiple doses of fabotherapy. 7, 9, 11, 18 Tests of the two groups were performed to determine if variables were present. For the children seen during the first period the average hospital stay was 10.4 days, whereas for the children of the second period the average hospital stay was 3.9 days. Hospitalization was notably longer for children of the first time period (Welch, P<0.001) (Wilcoxon, P<0.001). The variation of the outcomes was greater as a result of the treatment regimens during the first-period than when the pediatric patients received the fabotherapy (Bartlett, P= and Levene, P<0.001). Complications and sequelae Hematological complications were the most reported in the patients. These complications included hypoprothrombinemia, anemia, and infections. Comparison of the diverse types of complications among the children of the first and second periods (groups I y II) presented more frequently in children who received polyvalent anti-snake venom serum with higher protein content than that was administered in different modalities (Tables V, VI). Table V. Complications in group I*. Group I employing equine Complications serum (N.=30 patients) Frequency Percentage Anemia Hypofibrinogenemia Hypoprothrombinemia Infection at lesion site 7 8 Acute renal failure 1 1 Localized necrosis 7 8 Somnolence, paresthesias 8 9 Compartmental syndrome 5 6 Total complications Modified from Sotelo N. 11 The ratio of complications per patient was 2.72 and 1.69 for the first and second period, respectively (Pearson s χ 2 test, P=0.0932). The linear association between treatments and complications was (R 2, P=0.0187). Patient sequelae occurring was amputation of the second phalange of the middle finger of the right hand in 1 patient (1%), fasciotomyrelated keloid scars in 3 cases (3%), and necrosis-associated skin loss in the middle finger of the hand in 2 patients (2%). A 4-year-old patient treated during the first period received 5 vials of anti-snake venom serum and died 8 hours after admission to the emergency room. This patient presented with severe fourth-degree poisoning and subsequently developed multiple organ failure associated with disseminated intravascular coagulation (DIC). Discussion Table VI. Complications in group II. Group II fabotherapic Complications F(Ab ) 2 (N.=68 patients) Frequency Percentage Anemia Hypofibrinogenemia Hypoprothrombinemia Infection at lesion site Acute renal failure Localized necrosis Somnolence, paresthesias Compartmental syndrome Total complications Vol No. 2 Minerva Pediatrica 125

6 gation and toxicology. In pediatric patients, the frequency of snakebite is less common. There is a notable male predominance in snakebites of elementary school children and adolescents. However, in this paper, the proportion of bites in girls was 41%, and 59% of <10-years-old patients (more than one half were <5 years of age). Snakebites generally occurred at midday and in 70% of cases during the summer afternoon. This coincided with school vacations. The most frequently damaged anatomical areas were the lower limbs. It has been described that the degree of poisoning is more severe in the younger age groups and patients with lower weights. The degree of poisoning also depended upon the size and type of reptile. We observed that the worst effects occurred in children aged <5 years. One of the patients was an adolescent. The signs and symptoms and the use of the Christopher-Rodning Scale for degree of envenomation must be accurately reported. Usefulness of accurate reporting is necessary in order to make the appropriate treatment decision. 11, 18, 19, 21, 24 At our hospital, we have had the opportunity of treating 100 patients during a period of 37 years. This gave us the opportunity to acquire the knowledge required to use polyvalent equine anti-snake venom serum, employed up to 1996, and of the fabotherapy that we have used from 1997 to the present. With the latter, we have observed a statistically significant reduction of hospitalization time between the first period and the second of poisoning, with a reduction from 10.4 to 3.9 days (P<0.0001). In addition, during the periods, fasciotomy was required in only one patient with compartment syndrome. This patient received a lower anti-venom dose before being treated at our hospital. In recent years, there have been notable advances in the knowledge concerning the complexity of specific components and actions of the venoms in different organs and systems The production of tissue lesions, damage of the capillary endothelium, destruction of the cellular membranes, inflammation, rhabdomyolysis, musculoskeletal necrosis, pulmonary embolism, alveolar rupture, thirdspace formation, renal insufficiency, changes in arterial pressure, neurotoxicity, cardiotoxicity, as well as more exact causes of frequent hematological complications caused by the complex interaction of diverse components of the venom. These include metalloproteinases with their proteolytic and hemorrhagic activity, the effects of serine proteinases, thromboserpentine kalicreins and fibrinogenases which activate the factor X, impeding the fibrin-linked complex form, presenting an abnormal fibrin lesion due to the thrombinoserpentines, generating unstable coagulation. Snake-venom thrombin-like enzymes (SV- TLE) insures failure of the activation of factor X, which normally crosses the fibrin chains. This also causes hypofibrinogenemia. It is also known that phospholipase A 2 causes cytotoxicity, myonecrosis and hemolysis. This also acts hydrolytically on lectin, forming isolecitins. This destroys the erythrocytes and leads to intravascular hemolysis. Additionally, platelets are destroyed due to damage to the membrane of these cells Inflammation mediators are released, such as interleukin. Tumor necrosis factor-alpha, phosphatidases, and the lytic proteoenzymes, contained in the venoms favor the consumption of coagulation factors can even lead to DIC. This series of events, described very briefly, will disclose the diverse changes in bleeding tendency tests that we reported in our laboratory and are directly responsible for the hematological alterations that were present in the first and second groups of children evaluated. This paper compares the rates of complications. The latter occurred more frequently in children who received polyvalent anti-snake venom serum with higher protein content than that administered in different modalities. The ratio of complications per patient was 2.72 and 1.69 for the first and second periods reviewed, respectively (Pearson s χ 2 test, P=0.093). We did not observe recurrence phenomena in hematological alterations and toxicity, as it had been frequently reported in other series in which polyvalent anticroatilic serum of ovine 126 Minerva Pediatrica april 2017

7 (Fab O) was used. Other authors having experience in snakebite treatment have reported that with the use of continuous infusion a lesser dose is required and the risk of recurrence is avoided. 11, 19, 21, 23, Soft tissue infections are frequent complications of snakebite with localized poisoning. The proteolytic properties of snake venom cause an extensive destruction and devitalization of the soft tissue. This predisposes the wound to bacterial infection from the snake s indigenous oral flora. The role of prophylactic antibiotics to prevent this formation is controversial. However, according to authors and treatment guides, the prophylactic administration of antibiotics is recommended. 6, 7, 11, 20, 32, 36 In group II the number of infections is noteworthy. This is probably due to the new treatment protocols and the emphasis of lesion cultures. This, however, is an expected outcome with this type of occurrence In this series, there was evident reduction in hospitalization stay. This can be attributed to the use of fabotherapy, 37 which has permitted resolution with rapid improvement of the envenomation state. The use of fabotherapy in pediatric patients has avoided serious complications and fatal outcomes. However, fabotherapy is not available worldwide. 37. Unfortunately, the death rate from snakebites has not decreased substantially in Mexico. 1-4, 7, 38 Recently, the WHO launched an integrated strategy for the management of several neglected tropical diseases, all of which disproportionately affect the poorest populations in Africa, Latin American, Asia, and Guinea. The Global Snakebite Initiative ( snakebiteinitiative.org) associated with other international efforts will help to reduce the burden of this worldwide problem. 1, 39 Conclusions Rattlesnake (Crotalus spp.) bite is less frequent as compared to other viper species. The hematological complications are more frequent in this series of cases, however we did not observe any hematological recurrent phenomenons. References 1. Frayre-Torres MJ, Sevilla-Godínez E, Orozco-Valerio MDE, Armas J, Celis A. Mortalidad por contacto con serpientes y lagartos venenosos en México de Gac Med Mex 2006;42; Siria-Hernández CG, Arellano-Bravo A. Mordedura por serpientes: panorama epidemiológico en México. Salud Publ Méx 2010;51: González-Rivera A, Chico-Aldama P, Domínguez- Viveros W, Iracheta-Gerez ML, López-Alquicira M, Cuellar-Ramírez A, et al. Epidemiología de las mordeduras por serpientes. Su simbolismo. Acta Pediatr Mex 2009;30: Luna-Bauza M, Martínez Ponce G, Salazar-Hernández AC. Mordeduras por serpiente. Panorama epidemiológico de la zona de Córdova Veracrúz. Rev Fac Med UNAM 2004;47: Russell FE. Snake venom poisoning. Philadelphia PA: JB Lippincott; p Tokish JT, Benjamin J, Walter F. Crotalid envenomation: The southern Arizona experience. J Orthop Trauma 2001;15: Tay-Zavala J, Díaz-Sánchez JG, Sánchez-Vega JT, Ruíz-Sánchez D, Castillo L. Serpientes y reptiles de importancia médica en México. Rev Fac Med UNAM 2002;45: Janes DN,Bush SP, Kollura GR. Large snake size suggest increased snakebite severity in patients bitten by rattlesnake in Southern California. Wild Environ Med 2010;21: Sotelo-Cruz N, García-Alvarez R. Rattlesnake bite complications in 19 children. Pediatr Emerg Care 1994;10: Sotelo-Cruz N. Envenenamiento por mordedura de serpiente de cascabel, daños a la salud y tratamiento en la edad pediátrica. Gac Med Mex 2003;139: Sotelo N. Review of treatment and complications in 79 children with rattlesnake bite. Clin Pediatr 2008;47: Warrel DA. Snake bite. Lancet 2010;375: Mackessy SP. The field of reptile toxinology: snakes, lizards, and their venoms. In: Mackessy SP, editor. Handbook of venom and toxins of reptiles. Boca Raton: CRC Press, Taylor Francis Group; p Gutierrez JM, Rucavado A, Escalante T. Snake venom metalloproteinases, biological roles and participation in the pathophysiology of envenomation. In: Mackessy SP, editor. Handbook of venom and toxins of reptiles. Boca Raton: CRC Press, Taylor Francis Group; p Roodt AR, Estevez-Ramírez J, Paniagua-Solis JF, Litwin S, Carvajal-Saucedo A, Dolab JA, et al. Toxicidad de venenos de serpientes de importancia médica en México. Gac Med Mex 2005;141: Phillips DJ, Swenson SD, Markland FS. Thrombin-like snake venom serine proteinases. In: Mackessy SP, editor. Handbook of venom and toxins of reptiles. Boca Raton: CRC Press, Taylor Francis Group; p Christopher DG, Rodning CB. Crotalidae envenomation. South Med J 1986;79: Sotelo-Cruz N. El tratamiento de la mordedura por serpientes. Un enfoque práctico. Rev Mex Ped 1997;64: Gold SB, Barish RA, Dart CR. North American snake envenomation: diagnosis and management. Emerg Med Clin North Am 2004;22: Campbell BT, Corsi JM, Boneti C,Jakson RJ, Smith SD, Kokosa ER. Pediatric snakebites: lessons learned from 114 cases. J Pediatr Surg 2008;43: Ozay G, Bosnak M, Ece A, Davutoglu M, Dikici B, Vol No. 2 Minerva Pediatrica 127

8 Gurkan F, et al. Inicial characteristics of children with snakebite poisoning and management of complication in the pediatric intensive care unit. Pediatr Int 2005;47: Lavonas EJ, Khatri V, Daugherty C, Bucher-Barteloson B, King T, Dart RC. Medically significant late bleeding after treated crotaline envenomation: A systematic review. Ann Emerg Med 2014;63: Sotelo-Cruz N. Mordedura por serpiente venenosa. In: Martínez- Pantaleón O (ed) Intoxicaciones, Asociación Mexicana de Pediatría. Mc Graw-Hill Interamericana, México; p Corneille MG, Larson S, Stewart RM, Dent D, Myres JG, López PP, et al. A large single-center experience with treatment of patients with crotalid envenomations: outcomes with and evolution of antivenin therapy. Am J Surg 2006;192: Software JMP Version 10.0 (Academic). SAS Institute Inc;Cary NC,USA Dart RC, McNally J. Efficacy, safety and use snake antivenom in the United States. Ann Emerg Med 2001;37(2): Sánchez EE, Galan JA, Pérez JC, Rodríguez-Acosta A, Chase BP, Pérez JC. The efficacy of two antivenoms against the venom of North American snakes. Toxicon 2003;41: Seger D, Kahn S, Krenzelok EP. Treatment of US Crotalidae bites. Comparison of serum and globulin-based polyvalent and antigen-binding fragment antivenins. Toxicol Rev 2005;24: Richardson III WH, Tanen DA, Tong TC, Betten DP, Carstairs SD, Williams SR, et al. Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American Viperidae venoms in a murine model. Ann Emerg Med 2005;45: Wasserberger J, Ordog G, Merkin TE. Southern Pacific rattlesnake bite: a unique clinical challenge. J Emerg Med 2006;31: Goto CS, Yi-Feng S. Crotalidae polyvalent immune Fab for the treatment of pediatric crotaline envenomation. Pediatr Emer Care 2009;25: Guías de Práctica Clínica. Diagnóstico y tratamiento de la mordedura por serpientes venenosas. Catálogo maestro de Guías de Práctica Clínica. CENETEC. SSA, Secretaría de Salud México [Internet]. Available from: www. cenetec.salud.gob.mx/interior/gpc.htlm [cited 2016, Apr 20]. 33. Bush SP, Seifert SA, Oakes J, Smith SD, Phan TH, Pearl SR, et al. Continuos IV Crotalidae polyvalent immune Fab (Ovine)(FabAV) for selected North American rattlesnake bite patients. Toxicon 2013;69: Boyer LV, Chase PB, Degan JA, Figge G, Buelna-Romero A, Luchetti C, et al. Subacute coagulopathy in a randomized comparative trial of Fab and F(ab )2 antivenoms. Toxicon 2013;74: Camilleri C, Offerman S, Gosselin R, Alberston T. Conservative management of delayed, multicomponent coagulopathy following rattlesnake envenomation. Clin Toxicol (Phila) 2005;43: Garg A, Sujatha S, Garg J, Srinivas AN, Parija SC. Wound infections secondary to snakebite. J Infect Dev Ctries 2009;3: Wade L. For Mexican Antivenom Maker, U.S. Market Is a Snake Pit. Science 2014;343: García-Willis CE, Rivas-Castelán AR. Experiencia en el manejo de pacientes con mordedura de víbora en el Hospital General de Tampico. Reporte de 210 casos. Med Interna Mex 1997;13: Gutierrez JM, Warrel DA, Williams DJ, Jensen S, Brown N, Calvete JJ, et al. The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: the way forward. PLoS Negl Trop Dis 2013;7:e2162. Conflicts of interest. The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Acknowledgments. We wish to thank Ing. Ignacio Fonseca-Chong from University of Sonora for his assistance with statistical analysis and as well for his excellent suggestions. Manuscript accepted: July 27, Manuscript revised: July 22, Manuscript received: November 21, Minerva Pediatrica april 2017