Management of Pediatric Snake Bites: Are We Doing Too Much? Jesus A. Correa, Sara C. Fallon, Andrea T. Cruz, Glenda H. Grawe, Phong V. Vu, Daniel M. Rubalcava, Brent Kaziny, Bindi J. Naik-Mathuria, Mary L. Brandt PII: DOI: Reference:
S0022-3468(14)00052-9 doi: 10.1016/j.jpedsurg.2014.01.043 YJPSU 56674
To appear in:
Journal of Pediatric Surgery
Received date: Accepted date:
26 January 2014 27 January 2014
Please cite this article as: Correa Jesus A., Fallon Sara C., Cruz Andrea T., Grawe Glenda H., Vu Phong V., Rubalcava Daniel M., Kaziny Brent, Naik-Mathuria Bindi J., Brandt Mary L., Management of Pediatric Snake Bites: Are We Doing Too Much?, Journal of Pediatric Surgery (2014), doi: 10.1016/j.jpedsurg.2014.01.043
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Management of Pediatric Snake Bites: Are We Doing Too Much?
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Jesus A. Correa1, Sara C. Fallon1, Andrea T. Cruz2, Glenda H. Grawe2, Phong V. Vu2, Daniel M. Rubalcava2, Brent Kaziny2, Bindi J. Naik-Mathuria1, Mary L. Brandt1 1
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Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine 2
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Department of Pediatrics, Section of Emergency Medicine, Baylor College of Medicine, Houston, TX
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Mary L. Brandt MD Division of Pediatric Surgery Texas Children's Hospital 6701 Fannin CCC Suite 1210 Houston, TX 77030 Phone: 832 822 3135 Fax: 832 825 3141 E-mail: [email protected]
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Correspondence:
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Abstract
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Background
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The optimal management of children with snake bite injuries is not well defined. The purpose of this study was to review the use of antivenom, diagnostic tests, and antibiotics in children bitten by venomous snakes in a specific geographic region (Southeast Texas).
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Methods
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This is a retrospective single-center review of all patients with snake bite injury from 1/20066/2012. An envenomated bite was defined as causing edema, discoloration of the skin, necrosis, or systemic effects. The severity of injury was scored using a novel 4-point scale based on initial physical examination alone. Results
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Conclusion
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One hundred fifty-one children (mean age 8.4+4.3 years) were treated for a snake bite. There were no mortalities. Lower extremity injuries were most common (60%). Most bites were from copperheads (43%). Envenomation was evident in 82% (average wound score: 2.61+0.81). The median hospital stay for admitted patients (79%) was 2 days (range 1-7). Four patients required surgery for complications of the snake bite. Fifty-two children (34%) received CroFab, with one allergic reaction. 22/135 (16%) had evidence of coagulopathy. Seventy-two children (48%) received IV antibiotics.
Despite a high rate of envenomated bites in Southeast Texas, significant morbidity is rare. Children with an envenomation score of 1 or 2 are unlikely to be coagulopathic, suggesting that laboratory investigation should be reserved for patients with higher scores. The indications for the administration of CroFab deserve further prospective study.
Keywords: Pediatric; Envenomation; Snake Bite; Animal Bite; Antivenom
ACCEPTED MANUSCRIPT Background Snake bites are relatively uncommon in most regions of the United States, but represent
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an injury that may have significant associated potential morbidity or even mortality. Globally, it is estimated that over 2 million snakebites cause 20,000 to 94,000 deaths every year [1]. In the
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United States, approximately 3,000-6,000 snake bite envenomations occur every year, with an incidence of 0.79 to 1.14 per 100,000 people, resulting in only 5 deaths [1-3]. Geographic
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regions have different species of snakes, resulting in significant variability in the risk of
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morbidity and mortality. Serpents in the Crotalidae (pit viper) family cause 99% of snakebites in the United States. There are five subspecies of copperheads which are found from New England
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to Florida, west to Texas, and in the southern Midwest. The three subspecies of cottonmouths are most common in the southeastern US and along the Gulf Coast. There are over 60 subspecies of
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rattlesnakes, with a wide distribution from the Atlantic to the Pacific coasts at lower latitudes [4].
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Snake venom from pit vipers contains zinc-dependent metalloproteinases that cause
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direct damage to capillaries by disrupting the basement membrane-endothelial cell connections, causing hemorrhage and fluid extravasation [5]. Significant envenomation can lead to hypoperfusion of soft tissue and skeletal muscle which results in tissue necrosis. The venom of the Crotalidae subfamily, which includes rattlesnakes, copperheads, and cottonmouths/water moccasins, is hemotoxic [6-8]. The consumptive coagulopathy resulting from rattlesnake envenomation is presumably unresponsive to heparin and to fresh frozen plasma while the venom is still circulating, resulting in disseminated intravascular coagulation. The venom of the Elapid family snakes (coral snakes), works by a different mechanism as it contains alpha neurotoxins which cause direct neurotoxicity [5].
ACCEPTED MANUSCRIPT The majority of patients with envenomated snake bites present with painful swelling at the injury site and can be managed conservatively [9]. A smaller percentage of patients suffer
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more significant morbidity including consumptive coagulopathy, acute renal failure,
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hypovolemic shock, and anaphylaxis [7]. Children are at a higher risk of developing more serious injuries due to their smaller size and the higher relative concentrations of venom
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compared to adults.
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A paucity of prospective data has led to variation in management of pediatric snakebites.
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The use of antivenin (CroFab) and screening labs to detect abnormalities in coagulation has been recommended in patients with evidence of envenomation. However, there is no clear definition
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of envenomation in the literature, making it difficult to determine the efficacy of these proposed guidelines [4, 10]. The purpose of this study was to review a high-volume tertiary care
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experience with snakebites in a pediatric population, in order to examine current practice patterns
Methods
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and outcomes.
After obtaining IRB approval, the medical records of all patients < 18 years of age presenting to Texas Children’s Hospital (TCH) with a snake bite injury from 1/2006-6/2012 were reviewed. Texas Children’s Hospital is a tertiary care, level 1 trauma center in Houston, Texas with over 80,000 emergency department visits annually. Patients coded with an injury mechanism of snake bite were identified through a prospectively collected trauma database. Data collected included the age at presentation, the setting of the injury, the type of snake involved, physical exam findings, and the hospital course. Snake bites were defined as “envenomated” if
ACCEPTED MANUSCRIPT there was evidence of edema, discoloration of the site, necrosis, or systemic symptoms. The severity of injury was scored using a novel scale based only on the initial physical examination
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(Table 1). Patients with systemic symptoms such as neuralgia, paresthesias, paralysis, altered
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mental status and/or hypotension received automatic scores of 4, independent of local findings.
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Demographic characteristics and clinical and laboratory findings were calculated as percentages or means/medians for continuous variables. A priori analyses compared clinical and
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laboratory findings and outcomes of patients stratified by wound scale score and CroFab
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administration to assess management practices and resource utilization. Coagulopathy was defined as a PT> 15, INR>1.5, or a PTT>40. Creatine kinase (CK) was considered elevated if >
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240 IU/L. Analyses were conducted using SPSS Version 20 (IBM; Chicago, IL).
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Results
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Patient Population
During the study period, 151 children (66% male, mean age 8.4+4.3 years) were
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evaluated for snakebite in our institution (Table 2). Lower extremity injuries were most common (60%, n=91), followed by upper extremity (38%, n=58), groin (1%, n=1), and face (1%, n=1). The majority of our patients were transferred from referring facilities (n=121, 80%). Pediatric general surgery was consulted for assistance in management in 82 (54%) patients, and plastic surgery was consulted for wound management in 36 (24%); a small number of children received both general and plastic surgery consultation. The snake was identified by photo, description, or by examination of the snake (n=27) in 86 (57%) cases. Copperheads (n=65, 43%) were the most frequent, followed by water moccasins (n=6, 4%), rattlesnakes (n=6, 4%), coral snakes (n=3, 2%), pit vipers (n=3, 2%), pygmy rattlesnake (n=1, 1%), timber rattle snake (n=1, 1%), and fer-
ACCEPTED MANUSCRIPT de-lance (n=1, 1%). The snakebite occurred near the home in the majority (53%) of patients. 11 patients (7%) were bitten in a wilderness setting, and the setting of the bite was not documented
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in 60 (40%).
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Patient Outcomes
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Four patients required surgery: two fasciotomies for compartment syndrome, one fullthickness skin graft, and one operative wound debridement. No patients presented with or
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mentation. There were no deaths.
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developed hypotension, neurologic deficits, significant gastrointestinal symptoms, or altered
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Resource Utilization
We evaluated the management strategies and overall resource utilization with respect to
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laboratory investigation, antibiotic treatment, and antivenom administration based on wound score (Table 3). Thirty-four percent (n=52/154) received antivenom. Laboratory studies, including coagulation profile (89%), complete blood count (85%), creatinine kinase (23%), and urinalysis (2%) with microscopy (evaluating for myoglobinuria) were ordered in a significant number of patients. Of the 109 patients who had envenomated snake bites and were admitted, 81 patients were treated with intravenous antibiotic therapy. Patients with a wound score of 1 were treated with the full complement of IV antibiotics, laboratory evaluation, and antivenom 7% of the time, compared to 10%, 22%, and 21% for wound scores of 2, 3, and 4, respectively. Laboratory Evaluation
ACCEPTED MANUSCRIPT We analyzed the specific laboratory findings to determine the rates of anomalous values. Coagulation parameters are commonly ordered to assess for envenomation. Of the 135 patients
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with a coagulation panel obtained, 18% of patients had an abnormality. The highest values for
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PT, INR, and PTT were 20.2, 1.6, and 40.6, respectively. No patients had platelet levels less than 100,000 U/L. Myoglobinuria was detected in 3% (n=3), and elevation of CK was evident in 3%
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(n=1) of patients (Table 3).
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Antibiotic Utilization
In total, 44% (52/109) of admitted patients received IV antibiotics. 39% of all patients
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(59/151) were treated with oral antibiotics. Some patients received IV antibiotics as an inpatient,
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and were discharged with oral therapy. The specific antibiotic used for treatment varied. The most common drugs included clindamycin (14%), piperacillin/tazobactam (11%), and
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ticeracillin/sulbactam (7%) on an inpatient basis, and amoxicillin/clavulanate (25%),
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clindamycin (14%) and trimethoprim-sulfamethoxazole (4%) as an outpatient. There were no readmissions related to inadequately treated or recurrent skin infections.
Antivenom Administration Fifty-two patients (34%) received antivenom (generic name FabAV, trade name CroFab). There were no significant differences in patients who were treated with CroFab compared to those who were not (Table 2). The median dose was 6 vials (range = 1-16) for an estimated cost (based on the cost of one vial of CroFab in 2012) of $70,824 (range $11,804-$188,864). We
ACCEPTED MANUSCRIPT compared rates of antivenom administration between those patients presenting primarily to our institution and those referred from another center. The wound severity scale was similar between
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transferred patients (2.61+0.75) and patients with primary presentation (2.43+0.94, p=0.29). In
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the group of transferred patients, most (59%, n=71) did not receive antivenom at either the referral center or our institution. Of the 121 patients received in transfer from other institutions,
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17 (14%) were given antivenom prior to transfer, and 21 (17%) received antivenom after arrival
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to TCH. Patients who presented primarily to our hospital received antivenom infrequently (7%, n=2). Due to an evolving injury, 10% of patients were given antivenom at both institutions.
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Three of four children who required an operation for treatment were given antivenom prior to the
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surgery.
Approximately 35% of all patients received CroFab, indendent of the wound severity.
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(Table 3) However, the likelihood of receiving CroFab differed between patients transferred to
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TCH vs. patients seen primarily at TCH. Of the transferred patients with a wound score of 4, antivenom administration rate was highest at 64%, with a rate of 38% for a score of 3, 43% for a
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2, and 25% for a 1. Only one of two patients seen at TCH with a score of 4 received antivenom (50%), decreasing to rates of 15% for a score of 3, and 0% for scores of 2 or 1. There was only one allergic reaction (urticarial) to FabAV administered at an outside hospital. Discussion Proposed classifications of snakebite wounds described in the literature most often combine findings on physical examination with laboratory evidence of systemic envenomation. One group stratifies snakebite envenomations into “Minimal,” “Moderate,” and “Severe” categories, using the severity of the wound, systemic symptoms, and coagulation abnormalities
ACCEPTED MANUSCRIPT [3]. Another group bases the severity of envenomation on the presence of symptoms in multiple organ systems (pulmonary, cardiovascular, gastrointestinal, hematologic, and central nervous),
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and has less of an emphasis on wound appearance [4]. Neither scheme has been validated in a
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pediatric population. Our proposed classification method emphasizes physical findings of the wound, as the majority of patients did not have significant laboratory abnormalities or systemic
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symptoms despite a high rate of envenomation.
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Treatment algorithms for pediatric snake bite management are varied. Centers for
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Disease Control and Prevention recommendations include rapid transport for emergency care, seeking attention before symptoms appear, and avoidance of self-treatment [11]. Supportive care
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with intravenous fluids is recommended, and laboratory panels examining for evidence of developing coagulopathy may be drawn from the unaffected limb. Those who appear to be
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affected by a non-envenomated bite may be discharged after a period of observation [3, 10].
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When patients have signs and symptoms of envenomation, current recommendations include observation of the affected limb with the leading edge of edema demarcated and timed and
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measured every 30 minutes. The recommendations regarding who should receive antivenom are less clear. Antivenom is suggested when the clinical picture of the patient and supportive lab results indicate envenomation, but stratification based on severity of the bite is not well-defined. Consensus recommendations from a panel of experts in bite management include the use of antivenom when there is moderate or increased swelling, laboratory evidence of coagulopathy, or systemic signs. [12] Patients with potential coral snake envenomation should be treated differently due to the risks of respiratory muscle paralysis requiring emergency ventilation, and should immediately receive antivenom and supportive care. [13, 14]. The antivenom targeting coral snake bites, which is horse derived and of limited availability, is different than the standard
ACCEPTED MANUSCRIPT antivenom given to target crotalidae bites. If antivenom is given, CroFab is preferable to antivenin crotalidae polyvalent (ACP), as ACP is highly allergenic with a high risk of serum
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sickness (up to 75%) [15-18]. CroFab was first approved for treatment of minimal and
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moderate Crotaline envenomations in 2000 [19]. CroFab has a reported 14.3% reaction rate (all mild to moderate in severity), most commonly urticarial [20], though serum sickness has been
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reported [21]. In this series, only one patient had an urticarial reaction to CroFab. However, the
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favorable side effect profile reported in our series does not obviate judicious use of this medication—serum sickness remains a potentially devastating side effect of CroFab, and the
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effect on the patient’s clinical course.
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costs associated with administration of this drug are high, particularly given the uncertainty of its
The use of extensive laboratory investigation to direct clinical management deserves
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further scrutiny. Snake bite envenomations can cause coagulopathy by inducing
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hypofibrinogenemia, thrombocytopenia, prolonged INR and activated PTT, and increased fibrin degradation products [10]. However, the number of patients with severely disrupted coagulation
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profiles or clinical evidence of coagulopathy noted in our series was minimal. Our series may not be comparable to other geographic locations as copperheads caused nearly half of the identified injuries, and their venom is known to produce less severe effects than rattlesnake venom [3]. We recommend obtaining the full profile of laboratory test for childen bitten by an unidentified snake who live in an area where there is a higher probability of rattlesnake bites. For copperhead and cottonmouth bites, it may be more appropriate to order laboratory studies only if significant envenomation is suspected by exam or the presence of systemic symptoms, as those with more severe wounds or symptoms are more likely to have laboratory abnormalities.
ACCEPTED MANUSCRIPT The utility of prophylactic antibiotics in snakebites is controversial. For Crotalid bites, wound infection rates are 3%, and prophylactic antibiotics would have a marginal, if any benefit
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[22, 23]. A significant number of patients in our study received antibiotics, both in the hospital
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and at home after discharge. Given the retrospective nature of the study with limited follow-up, it is difficult to determine the impact on patient outcome. However, it has been argued that
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empirical use of antibiotics has little use in the care of patients bitten by snakes, and we question
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the utility of its administration in milder injuries.[3, 24, 25]
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To our knowledge, this study presents the findings of the largest group of pediatric patients treated for envenomated snakebites since CroFab was introduced. Our results support
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that envenomation from copperheads and cottonmouths can be managed more conservatively than currently published recommendations. Patients with envenomated rattlesnake and coral
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snake bites are at greater risk for serious sequelae and should receive antivenom [3, 13, 26]. It is
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reasonable, if the snake was not identified, to administer antivenom for suspected envenomated
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snake bites, particularly in regions where rattlesnakes are common. There were limitations to this retrospective study. The wound severity score was calculated retrospectively based on documentation after the child arrived to Texas Children’s Hospital. The appearance of a snakebite wound will progress with time. We anticipate that further refinement of our wound classification and treatment algorithm will take this into account. Additionally, it was difficult to account for patient size in this review. Smaller patients may benefit from differential management, as less severe bites may have greater systemic consequences. A prospective study would better assess certain patient specific variables that may require alterations in the management algorithm. Laboratory evaluation and management were not standardized, and the rationale for administration of antibiotics and CroFab was not always
ACCEPTED MANUSCRIPT discernible from the medical record. In our community, the majority of bites where the snake could be identified were inflicted by copperheads. Given the great geographic variability of
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snake species in the United States, we recommend consulting local and regional species
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distributional maps (Figures 2-4) when considering appropriate algorithms for the treatment of
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snakebites.
Despite a high rate of envenomated bites (~80% in our series), severe morbidity meriting
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fasciotomy or extensive treatment with CroFab is rare. We found that the majority of children
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with envenomated snake bites recovered well with supportive care and elevation of the affected limb, without administration of CroFab. Given these data, we have proposed a management
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algorithm specific to pediatric patients treated at tertiary care centers to standardize therapy and optimize interventions. (Figure 1). Patients with suspected rattlesnake or coral snake bites (2%
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of our series) and patients with evidence of systemic symptoms (13% of our series) would not be
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treated according to this algorithm and would undergo the complete laboratory panel, receive antivenom and would most likely be admitted to a higher level of care such as the intensive care
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unit. Antibiotic administration in our proposed algorithm is based on the presence of cellulitis or necrosis. Importantly, we recognize that this proposed algorithm may not be valid in all locations and must be validated before it can be widely implemented.
ACCEPTED MANUSCRIPT References:
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17. 18. 19. 20. 21. 22. 23.
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Kasturiratne, A., et al., The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med, 2008. 5(11): p. e218. Langley, R.L. and W.E. Morrow, Deaths resulting from animal attacks in the United States. Wilderness Environ Med, 1997. 8(1): p. 8-16. Gold, B.S., R.C. Dart, and R.A. Barish, Bites of venomous snakes. N Engl J Med, 2002. 347(5): p. 347-56. Dart, R.C., et al., Validation of a severity score for the assessment of crotalid snakebite. Ann Emerg Med, 1996. 27(3): p. 321-6. Gutierrez, J.M. and A. Rucavado, Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage. Biochimie, 2000. 82(9-10): p. 841-50. Persson, H., Envenoming by European vipers antivenom treatment--influence on morbidity. Przegl Lek, 2001. 58(4): p. 223-5. Juarez, P., L. Sanz, and J.J. Calvete, Snake venomics: characterization of protein families in Sistrurus barbouri venom by cysteine mapping, N-terminal sequencing, and tandem mass spectrometry analysis. Proteomics, 2004. 4(2): p. 327-38. Warrell, D.A., Commissioned article: management of exotic snakebites. QJM, 2009. 102(9): p. 593-601. Campbell, B.T., et al., Pediatric snakebites: lessons learned from 114 cases. J Pediatr Surg, 2008. 43(7): p. 1338-41. Goto, C.S. and S.Y. Feng, Crotalidae polyvalent immune Fab for the treatment of pediatric crotaline envenomation. Pediatr Emerg Care, 2009. 25(4): p. 273-9; quiz 280-2. Prevention, C.f.D.C.a. Venomous Snakes. 2012 [cited 2012 December 4th]; Available from: http://www.cdc.gov/niosh/topics/snakes/. Lavonas, E.J., et al., Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med, 2011. 11: p. 2. Kitchens, C.S. and L.H. Van Mierop, Envenomation by the Eastern coral snake (Micrurus fulvius fulvius). A study of 39 victims. JAMA, 1987. 258(12): p. 1615-8. Morgan, D.L., et al., Texas coral snake (Micrurus tener) bites. South Med J, 2007. 100(2): p. 152-6. Corrigan P, R.F., Wainschel J, Clinical reactions to antivenin. Toxicon, 1978: p. 457-465. Consroe, P., et al., Comparison of a new ovine antigen binding fragment (Fab) antivenin for United States Crotalidae with the commercial antivenin for protection against venom-induced lethality in mice. Am J Trop Med Hyg, 1995. 53(5): p. 507-10. Dart, R.C. and J. McNally, Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med, 2001. 37(2): p. 181-8. Bush, S.P., V.H. Wu, and S.W. Corbett, Rattlesnake venom-induced thrombocytopenia response to Antivenin (Crotalidae) Polyvalent: a case series. Acad Emerg Med, 2000. 7(2): p. 181-5. insert, P., CroFab (Crotalidae polyvalent immune fab (ovine), Protherics, Editor. 2002: Brentwood, TN. Ruha, A.M., et al., Initial postmarketing experience with crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation. Ann Emerg Med, 2002. 39(6): p. 609-15. Johnson, P.N., L. McGoodwin, and W. Banner, Jr., Utilisation of Crotalidae polyvalent immune fab (ovine) for Viperidae envenomations in children. Emerg Med J, 2008. 25(12): p. 793-8. Wingert, W.A. and L. Chan, Rattlesnake bites in southern California and rationale for recommended treatment. West J Med, 1988. 148(1): p. 37-44. Hall, E.L., Role of surgical intervention in the management of crotaline snake envenomation. Ann Emerg Med, 2001. 37(2): p. 175-80.
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Clark, R.F., B.S. Selden, and B. Furbee, The incidence of wound infection following crotalid envenomation. J Emerg Med, 1993. 11(5): p. 583-6. Kerrigan, K.R., et al., Antibiotic prophylaxis for pit viper envenomation: prospective, controlled trial. World J Surg, 1997. 21(4): p. 369-72; discussion 372-3. Vital Brazil O, F.M., Pellegrini FIlho A, Physiopathologie et therapeutique de l'envenomation experimentale causee par le venin de Micrurus frontalis. Mem Inst Butantan, 1976. 40: p. 221240.
Figure and Table Legends:
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Table 1: Texas Children’s Hospital novel classification system for the severity of snake bite wounds
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Table 2: Demographic, clinical, and laboratory characteristics of the study population Table 3: Resource utilization stratified by wound severity score
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Figure 1: Proposed clinical algorithm for snake bite management
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Figure 2. Distribution of the Western diamondback rattlesnake (Crotalus atrox) in the United States. Used with permission from NatureServe. 2013. NatureServe Explorer: An online encyclopedia of life [web application]. Version 7.1. NatureServe, Arlington, Virginia. Available http://www.natureserve.org/explorer. (Accessed: July 25, 2013).
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Figure 3. Distribution of Copperhead snakes (Agkistrodon contortrix) in the United States. Used with permission from NatureServe. 2013. NatureServe Explorer: An online encyclopedia of life [web application]. Version 7.1. NatureServe, Arlington, Virginia. Available http://www.natureserve.org/explorer. (Accessed: July 25, 2013). Figure 4. Distribution of Cottonmouth snakes (Agkistrodon piscivorus). Used with permission from NatureServe. 2013. NatureServe Explorer: An online encyclopedia of life [web application]. Version 7.1. NatureServe, Arlington, Virginia. Available http://www.natureserve.org/explorer. (Accessed: July 25, 2013).
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Description Minor injury Puncture marks only Moderate injury Puncture marks Cellulitis or ecchymosis localized to puncture marks Level 2 Findings +Spreading erythema, induration, or purulent material -Necrosis Level 3 Findings +Tissue necrosis *Systemic symptoms (neurologic, cardiovascular, gastrointestinal) irrespective of local findings.
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Wound Class 1
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Type of Snake
4%
4%
0.83
4% 4% 6%
4% 1% 3%
42%
43%
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83%
81%
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9% 33% 48% 10% 18%
10% 37% 44% 10% 17%
9% 31% 50% 10% 18%
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80%
81%
79%
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2 days Range 1-7
2 (range 1-5)
1 (range 1-7)
0.07
65 6 6 3 6
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Signs of envenomation 1 WSS 2 3 4 Coagulopath y Admitted to Hospital Median Length of Hospital stay (admitted patients) WSS: wound severity score
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42% 58% 64% 35% 1% 40%
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Water moccasins Rattlesnakes Coral Snake Other identified (venomous) snake Unidentified snake
Did not receive CroFab (n=103) 30% 70% 58% 41% 2% 44%
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Site of Bite
Female Male Leg Arm Other Copperhead
Received CroFab (n=48)
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Gender
Total population (n=151) Number (%) 52 (34%) 99 (66%) 91 57
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Variable
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Table 2: Demographic, clinical, and laboratory characteristics of the study population
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14%
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28%
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1/20 (5%) 54% 90%
0% 71% 80%
37% 0%
32% 0%
36% 4/15 (27%)
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0% 39% 74%
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Intervention CBC Thrombocytopenic (
S0022-3468(14)00052-9 doi: 10.1016/j.jpedsurg.2014.01.043 YJPSU 56674
To appear in:
Journal of Pediatric Surgery
Received date: Accepted date:
26 January 2014 27 January 2014
Please cite this article as: Correa Jesus A., Fallon Sara C., Cruz Andrea T., Grawe Glenda H., Vu Phong V., Rubalcava Daniel M., Kaziny Brent, Naik-Mathuria Bindi J., Brandt Mary L., Management of Pediatric Snake Bites: Are We Doing Too Much?, Journal of Pediatric Surgery (2014), doi: 10.1016/j.jpedsurg.2014.01.043
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ACCEPTED MANUSCRIPT Management of Pediatric Snake Bites: Are We Doing Too Much?
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Jesus A. Correa1, Sara C. Fallon1, Andrea T. Cruz2, Glenda H. Grawe2, Phong V. Vu2, Daniel M. Rubalcava2, Brent Kaziny2, Bindi J. Naik-Mathuria1, Mary L. Brandt1 1
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Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine 2
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Department of Pediatrics, Section of Emergency Medicine, Baylor College of Medicine, Houston, TX
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Mary L. Brandt MD Division of Pediatric Surgery Texas Children's Hospital 6701 Fannin CCC Suite 1210 Houston, TX 77030 Phone: 832 822 3135 Fax: 832 825 3141 E-mail: [email protected]
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Correspondence:
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Abstract
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Background
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The optimal management of children with snake bite injuries is not well defined. The purpose of this study was to review the use of antivenom, diagnostic tests, and antibiotics in children bitten by venomous snakes in a specific geographic region (Southeast Texas).
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Methods
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This is a retrospective single-center review of all patients with snake bite injury from 1/20066/2012. An envenomated bite was defined as causing edema, discoloration of the skin, necrosis, or systemic effects. The severity of injury was scored using a novel 4-point scale based on initial physical examination alone. Results
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Conclusion
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One hundred fifty-one children (mean age 8.4+4.3 years) were treated for a snake bite. There were no mortalities. Lower extremity injuries were most common (60%). Most bites were from copperheads (43%). Envenomation was evident in 82% (average wound score: 2.61+0.81). The median hospital stay for admitted patients (79%) was 2 days (range 1-7). Four patients required surgery for complications of the snake bite. Fifty-two children (34%) received CroFab, with one allergic reaction. 22/135 (16%) had evidence of coagulopathy. Seventy-two children (48%) received IV antibiotics.
Despite a high rate of envenomated bites in Southeast Texas, significant morbidity is rare. Children with an envenomation score of 1 or 2 are unlikely to be coagulopathic, suggesting that laboratory investigation should be reserved for patients with higher scores. The indications for the administration of CroFab deserve further prospective study.
Keywords: Pediatric; Envenomation; Snake Bite; Animal Bite; Antivenom
ACCEPTED MANUSCRIPT Background Snake bites are relatively uncommon in most regions of the United States, but represent
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an injury that may have significant associated potential morbidity or even mortality. Globally, it is estimated that over 2 million snakebites cause 20,000 to 94,000 deaths every year [1]. In the
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United States, approximately 3,000-6,000 snake bite envenomations occur every year, with an incidence of 0.79 to 1.14 per 100,000 people, resulting in only 5 deaths [1-3]. Geographic
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regions have different species of snakes, resulting in significant variability in the risk of
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morbidity and mortality. Serpents in the Crotalidae (pit viper) family cause 99% of snakebites in the United States. There are five subspecies of copperheads which are found from New England
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to Florida, west to Texas, and in the southern Midwest. The three subspecies of cottonmouths are most common in the southeastern US and along the Gulf Coast. There are over 60 subspecies of
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rattlesnakes, with a wide distribution from the Atlantic to the Pacific coasts at lower latitudes [4].
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Snake venom from pit vipers contains zinc-dependent metalloproteinases that cause
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direct damage to capillaries by disrupting the basement membrane-endothelial cell connections, causing hemorrhage and fluid extravasation [5]. Significant envenomation can lead to hypoperfusion of soft tissue and skeletal muscle which results in tissue necrosis. The venom of the Crotalidae subfamily, which includes rattlesnakes, copperheads, and cottonmouths/water moccasins, is hemotoxic [6-8]. The consumptive coagulopathy resulting from rattlesnake envenomation is presumably unresponsive to heparin and to fresh frozen plasma while the venom is still circulating, resulting in disseminated intravascular coagulation. The venom of the Elapid family snakes (coral snakes), works by a different mechanism as it contains alpha neurotoxins which cause direct neurotoxicity [5].
ACCEPTED MANUSCRIPT The majority of patients with envenomated snake bites present with painful swelling at the injury site and can be managed conservatively [9]. A smaller percentage of patients suffer
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more significant morbidity including consumptive coagulopathy, acute renal failure,
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hypovolemic shock, and anaphylaxis [7]. Children are at a higher risk of developing more serious injuries due to their smaller size and the higher relative concentrations of venom
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compared to adults.
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A paucity of prospective data has led to variation in management of pediatric snakebites.
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The use of antivenin (CroFab) and screening labs to detect abnormalities in coagulation has been recommended in patients with evidence of envenomation. However, there is no clear definition
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of envenomation in the literature, making it difficult to determine the efficacy of these proposed guidelines [4, 10]. The purpose of this study was to review a high-volume tertiary care
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experience with snakebites in a pediatric population, in order to examine current practice patterns
Methods
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and outcomes.
After obtaining IRB approval, the medical records of all patients < 18 years of age presenting to Texas Children’s Hospital (TCH) with a snake bite injury from 1/2006-6/2012 were reviewed. Texas Children’s Hospital is a tertiary care, level 1 trauma center in Houston, Texas with over 80,000 emergency department visits annually. Patients coded with an injury mechanism of snake bite were identified through a prospectively collected trauma database. Data collected included the age at presentation, the setting of the injury, the type of snake involved, physical exam findings, and the hospital course. Snake bites were defined as “envenomated” if
ACCEPTED MANUSCRIPT there was evidence of edema, discoloration of the site, necrosis, or systemic symptoms. The severity of injury was scored using a novel scale based only on the initial physical examination
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(Table 1). Patients with systemic symptoms such as neuralgia, paresthesias, paralysis, altered
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mental status and/or hypotension received automatic scores of 4, independent of local findings.
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Demographic characteristics and clinical and laboratory findings were calculated as percentages or means/medians for continuous variables. A priori analyses compared clinical and
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laboratory findings and outcomes of patients stratified by wound scale score and CroFab
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administration to assess management practices and resource utilization. Coagulopathy was defined as a PT> 15, INR>1.5, or a PTT>40. Creatine kinase (CK) was considered elevated if >
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240 IU/L. Analyses were conducted using SPSS Version 20 (IBM; Chicago, IL).
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Results
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Patient Population
During the study period, 151 children (66% male, mean age 8.4+4.3 years) were
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evaluated for snakebite in our institution (Table 2). Lower extremity injuries were most common (60%, n=91), followed by upper extremity (38%, n=58), groin (1%, n=1), and face (1%, n=1). The majority of our patients were transferred from referring facilities (n=121, 80%). Pediatric general surgery was consulted for assistance in management in 82 (54%) patients, and plastic surgery was consulted for wound management in 36 (24%); a small number of children received both general and plastic surgery consultation. The snake was identified by photo, description, or by examination of the snake (n=27) in 86 (57%) cases. Copperheads (n=65, 43%) were the most frequent, followed by water moccasins (n=6, 4%), rattlesnakes (n=6, 4%), coral snakes (n=3, 2%), pit vipers (n=3, 2%), pygmy rattlesnake (n=1, 1%), timber rattle snake (n=1, 1%), and fer-
ACCEPTED MANUSCRIPT de-lance (n=1, 1%). The snakebite occurred near the home in the majority (53%) of patients. 11 patients (7%) were bitten in a wilderness setting, and the setting of the bite was not documented
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in 60 (40%).
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Patient Outcomes
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Four patients required surgery: two fasciotomies for compartment syndrome, one fullthickness skin graft, and one operative wound debridement. No patients presented with or
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mentation. There were no deaths.
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developed hypotension, neurologic deficits, significant gastrointestinal symptoms, or altered
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Resource Utilization
We evaluated the management strategies and overall resource utilization with respect to
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laboratory investigation, antibiotic treatment, and antivenom administration based on wound score (Table 3). Thirty-four percent (n=52/154) received antivenom. Laboratory studies, including coagulation profile (89%), complete blood count (85%), creatinine kinase (23%), and urinalysis (2%) with microscopy (evaluating for myoglobinuria) were ordered in a significant number of patients. Of the 109 patients who had envenomated snake bites and were admitted, 81 patients were treated with intravenous antibiotic therapy. Patients with a wound score of 1 were treated with the full complement of IV antibiotics, laboratory evaluation, and antivenom 7% of the time, compared to 10%, 22%, and 21% for wound scores of 2, 3, and 4, respectively. Laboratory Evaluation
ACCEPTED MANUSCRIPT We analyzed the specific laboratory findings to determine the rates of anomalous values. Coagulation parameters are commonly ordered to assess for envenomation. Of the 135 patients
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with a coagulation panel obtained, 18% of patients had an abnormality. The highest values for
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PT, INR, and PTT were 20.2, 1.6, and 40.6, respectively. No patients had platelet levels less than 100,000 U/L. Myoglobinuria was detected in 3% (n=3), and elevation of CK was evident in 3%
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(n=1) of patients (Table 3).
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Antibiotic Utilization
In total, 44% (52/109) of admitted patients received IV antibiotics. 39% of all patients
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(59/151) were treated with oral antibiotics. Some patients received IV antibiotics as an inpatient,
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and were discharged with oral therapy. The specific antibiotic used for treatment varied. The most common drugs included clindamycin (14%), piperacillin/tazobactam (11%), and
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ticeracillin/sulbactam (7%) on an inpatient basis, and amoxicillin/clavulanate (25%),
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clindamycin (14%) and trimethoprim-sulfamethoxazole (4%) as an outpatient. There were no readmissions related to inadequately treated or recurrent skin infections.
Antivenom Administration Fifty-two patients (34%) received antivenom (generic name FabAV, trade name CroFab). There were no significant differences in patients who were treated with CroFab compared to those who were not (Table 2). The median dose was 6 vials (range = 1-16) for an estimated cost (based on the cost of one vial of CroFab in 2012) of $70,824 (range $11,804-$188,864). We
ACCEPTED MANUSCRIPT compared rates of antivenom administration between those patients presenting primarily to our institution and those referred from another center. The wound severity scale was similar between
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transferred patients (2.61+0.75) and patients with primary presentation (2.43+0.94, p=0.29). In
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the group of transferred patients, most (59%, n=71) did not receive antivenom at either the referral center or our institution. Of the 121 patients received in transfer from other institutions,
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17 (14%) were given antivenom prior to transfer, and 21 (17%) received antivenom after arrival
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to TCH. Patients who presented primarily to our hospital received antivenom infrequently (7%, n=2). Due to an evolving injury, 10% of patients were given antivenom at both institutions.
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Three of four children who required an operation for treatment were given antivenom prior to the
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surgery.
Approximately 35% of all patients received CroFab, indendent of the wound severity.
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(Table 3) However, the likelihood of receiving CroFab differed between patients transferred to
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TCH vs. patients seen primarily at TCH. Of the transferred patients with a wound score of 4, antivenom administration rate was highest at 64%, with a rate of 38% for a score of 3, 43% for a
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2, and 25% for a 1. Only one of two patients seen at TCH with a score of 4 received antivenom (50%), decreasing to rates of 15% for a score of 3, and 0% for scores of 2 or 1. There was only one allergic reaction (urticarial) to FabAV administered at an outside hospital. Discussion Proposed classifications of snakebite wounds described in the literature most often combine findings on physical examination with laboratory evidence of systemic envenomation. One group stratifies snakebite envenomations into “Minimal,” “Moderate,” and “Severe” categories, using the severity of the wound, systemic symptoms, and coagulation abnormalities
ACCEPTED MANUSCRIPT [3]. Another group bases the severity of envenomation on the presence of symptoms in multiple organ systems (pulmonary, cardiovascular, gastrointestinal, hematologic, and central nervous),
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and has less of an emphasis on wound appearance [4]. Neither scheme has been validated in a
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pediatric population. Our proposed classification method emphasizes physical findings of the wound, as the majority of patients did not have significant laboratory abnormalities or systemic
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symptoms despite a high rate of envenomation.
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Treatment algorithms for pediatric snake bite management are varied. Centers for
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Disease Control and Prevention recommendations include rapid transport for emergency care, seeking attention before symptoms appear, and avoidance of self-treatment [11]. Supportive care
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with intravenous fluids is recommended, and laboratory panels examining for evidence of developing coagulopathy may be drawn from the unaffected limb. Those who appear to be
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affected by a non-envenomated bite may be discharged after a period of observation [3, 10].
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When patients have signs and symptoms of envenomation, current recommendations include observation of the affected limb with the leading edge of edema demarcated and timed and
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measured every 30 minutes. The recommendations regarding who should receive antivenom are less clear. Antivenom is suggested when the clinical picture of the patient and supportive lab results indicate envenomation, but stratification based on severity of the bite is not well-defined. Consensus recommendations from a panel of experts in bite management include the use of antivenom when there is moderate or increased swelling, laboratory evidence of coagulopathy, or systemic signs. [12] Patients with potential coral snake envenomation should be treated differently due to the risks of respiratory muscle paralysis requiring emergency ventilation, and should immediately receive antivenom and supportive care. [13, 14]. The antivenom targeting coral snake bites, which is horse derived and of limited availability, is different than the standard
ACCEPTED MANUSCRIPT antivenom given to target crotalidae bites. If antivenom is given, CroFab is preferable to antivenin crotalidae polyvalent (ACP), as ACP is highly allergenic with a high risk of serum
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sickness (up to 75%) [15-18]. CroFab was first approved for treatment of minimal and
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moderate Crotaline envenomations in 2000 [19]. CroFab has a reported 14.3% reaction rate (all mild to moderate in severity), most commonly urticarial [20], though serum sickness has been
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reported [21]. In this series, only one patient had an urticarial reaction to CroFab. However, the
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favorable side effect profile reported in our series does not obviate judicious use of this medication—serum sickness remains a potentially devastating side effect of CroFab, and the
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effect on the patient’s clinical course.
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costs associated with administration of this drug are high, particularly given the uncertainty of its
The use of extensive laboratory investigation to direct clinical management deserves
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further scrutiny. Snake bite envenomations can cause coagulopathy by inducing
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hypofibrinogenemia, thrombocytopenia, prolonged INR and activated PTT, and increased fibrin degradation products [10]. However, the number of patients with severely disrupted coagulation
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profiles or clinical evidence of coagulopathy noted in our series was minimal. Our series may not be comparable to other geographic locations as copperheads caused nearly half of the identified injuries, and their venom is known to produce less severe effects than rattlesnake venom [3]. We recommend obtaining the full profile of laboratory test for childen bitten by an unidentified snake who live in an area where there is a higher probability of rattlesnake bites. For copperhead and cottonmouth bites, it may be more appropriate to order laboratory studies only if significant envenomation is suspected by exam or the presence of systemic symptoms, as those with more severe wounds or symptoms are more likely to have laboratory abnormalities.
ACCEPTED MANUSCRIPT The utility of prophylactic antibiotics in snakebites is controversial. For Crotalid bites, wound infection rates are 3%, and prophylactic antibiotics would have a marginal, if any benefit
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[22, 23]. A significant number of patients in our study received antibiotics, both in the hospital
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and at home after discharge. Given the retrospective nature of the study with limited follow-up, it is difficult to determine the impact on patient outcome. However, it has been argued that
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empirical use of antibiotics has little use in the care of patients bitten by snakes, and we question
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the utility of its administration in milder injuries.[3, 24, 25]
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To our knowledge, this study presents the findings of the largest group of pediatric patients treated for envenomated snakebites since CroFab was introduced. Our results support
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that envenomation from copperheads and cottonmouths can be managed more conservatively than currently published recommendations. Patients with envenomated rattlesnake and coral
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snake bites are at greater risk for serious sequelae and should receive antivenom [3, 13, 26]. It is
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reasonable, if the snake was not identified, to administer antivenom for suspected envenomated
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snake bites, particularly in regions where rattlesnakes are common. There were limitations to this retrospective study. The wound severity score was calculated retrospectively based on documentation after the child arrived to Texas Children’s Hospital. The appearance of a snakebite wound will progress with time. We anticipate that further refinement of our wound classification and treatment algorithm will take this into account. Additionally, it was difficult to account for patient size in this review. Smaller patients may benefit from differential management, as less severe bites may have greater systemic consequences. A prospective study would better assess certain patient specific variables that may require alterations in the management algorithm. Laboratory evaluation and management were not standardized, and the rationale for administration of antibiotics and CroFab was not always
ACCEPTED MANUSCRIPT discernible from the medical record. In our community, the majority of bites where the snake could be identified were inflicted by copperheads. Given the great geographic variability of
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snake species in the United States, we recommend consulting local and regional species
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distributional maps (Figures 2-4) when considering appropriate algorithms for the treatment of
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snakebites.
Despite a high rate of envenomated bites (~80% in our series), severe morbidity meriting
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fasciotomy or extensive treatment with CroFab is rare. We found that the majority of children
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with envenomated snake bites recovered well with supportive care and elevation of the affected limb, without administration of CroFab. Given these data, we have proposed a management
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algorithm specific to pediatric patients treated at tertiary care centers to standardize therapy and optimize interventions. (Figure 1). Patients with suspected rattlesnake or coral snake bites (2%
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of our series) and patients with evidence of systemic symptoms (13% of our series) would not be
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treated according to this algorithm and would undergo the complete laboratory panel, receive antivenom and would most likely be admitted to a higher level of care such as the intensive care
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unit. Antibiotic administration in our proposed algorithm is based on the presence of cellulitis or necrosis. Importantly, we recognize that this proposed algorithm may not be valid in all locations and must be validated before it can be widely implemented.
ACCEPTED MANUSCRIPT References:
8. 9. 10. 11. 12.
13. 14. 15. 16.
17. 18. 19. 20. 21. 22. 23.
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Kasturiratne, A., et al., The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med, 2008. 5(11): p. e218. Langley, R.L. and W.E. Morrow, Deaths resulting from animal attacks in the United States. Wilderness Environ Med, 1997. 8(1): p. 8-16. Gold, B.S., R.C. Dart, and R.A. Barish, Bites of venomous snakes. N Engl J Med, 2002. 347(5): p. 347-56. Dart, R.C., et al., Validation of a severity score for the assessment of crotalid snakebite. Ann Emerg Med, 1996. 27(3): p. 321-6. Gutierrez, J.M. and A. Rucavado, Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage. Biochimie, 2000. 82(9-10): p. 841-50. Persson, H., Envenoming by European vipers antivenom treatment--influence on morbidity. Przegl Lek, 2001. 58(4): p. 223-5. Juarez, P., L. Sanz, and J.J. Calvete, Snake venomics: characterization of protein families in Sistrurus barbouri venom by cysteine mapping, N-terminal sequencing, and tandem mass spectrometry analysis. Proteomics, 2004. 4(2): p. 327-38. Warrell, D.A., Commissioned article: management of exotic snakebites. QJM, 2009. 102(9): p. 593-601. Campbell, B.T., et al., Pediatric snakebites: lessons learned from 114 cases. J Pediatr Surg, 2008. 43(7): p. 1338-41. Goto, C.S. and S.Y. Feng, Crotalidae polyvalent immune Fab for the treatment of pediatric crotaline envenomation. Pediatr Emerg Care, 2009. 25(4): p. 273-9; quiz 280-2. Prevention, C.f.D.C.a. Venomous Snakes. 2012 [cited 2012 December 4th]; Available from: http://www.cdc.gov/niosh/topics/snakes/. Lavonas, E.J., et al., Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med, 2011. 11: p. 2. Kitchens, C.S. and L.H. Van Mierop, Envenomation by the Eastern coral snake (Micrurus fulvius fulvius). A study of 39 victims. JAMA, 1987. 258(12): p. 1615-8. Morgan, D.L., et al., Texas coral snake (Micrurus tener) bites. South Med J, 2007. 100(2): p. 152-6. Corrigan P, R.F., Wainschel J, Clinical reactions to antivenin. Toxicon, 1978: p. 457-465. Consroe, P., et al., Comparison of a new ovine antigen binding fragment (Fab) antivenin for United States Crotalidae with the commercial antivenin for protection against venom-induced lethality in mice. Am J Trop Med Hyg, 1995. 53(5): p. 507-10. Dart, R.C. and J. McNally, Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med, 2001. 37(2): p. 181-8. Bush, S.P., V.H. Wu, and S.W. Corbett, Rattlesnake venom-induced thrombocytopenia response to Antivenin (Crotalidae) Polyvalent: a case series. Acad Emerg Med, 2000. 7(2): p. 181-5. insert, P., CroFab (Crotalidae polyvalent immune fab (ovine), Protherics, Editor. 2002: Brentwood, TN. Ruha, A.M., et al., Initial postmarketing experience with crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation. Ann Emerg Med, 2002. 39(6): p. 609-15. Johnson, P.N., L. McGoodwin, and W. Banner, Jr., Utilisation of Crotalidae polyvalent immune fab (ovine) for Viperidae envenomations in children. Emerg Med J, 2008. 25(12): p. 793-8. Wingert, W.A. and L. Chan, Rattlesnake bites in southern California and rationale for recommended treatment. West J Med, 1988. 148(1): p. 37-44. Hall, E.L., Role of surgical intervention in the management of crotaline snake envenomation. Ann Emerg Med, 2001. 37(2): p. 175-80.
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Clark, R.F., B.S. Selden, and B. Furbee, The incidence of wound infection following crotalid envenomation. J Emerg Med, 1993. 11(5): p. 583-6. Kerrigan, K.R., et al., Antibiotic prophylaxis for pit viper envenomation: prospective, controlled trial. World J Surg, 1997. 21(4): p. 369-72; discussion 372-3. Vital Brazil O, F.M., Pellegrini FIlho A, Physiopathologie et therapeutique de l'envenomation experimentale causee par le venin de Micrurus frontalis. Mem Inst Butantan, 1976. 40: p. 221240.
Figure and Table Legends:
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Table 1: Texas Children’s Hospital novel classification system for the severity of snake bite wounds
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Table 2: Demographic, clinical, and laboratory characteristics of the study population Table 3: Resource utilization stratified by wound severity score
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Figure 1: Proposed clinical algorithm for snake bite management
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Figure 2. Distribution of the Western diamondback rattlesnake (Crotalus atrox) in the United States. Used with permission from NatureServe. 2013. NatureServe Explorer: An online encyclopedia of life [web application]. Version 7.1. NatureServe, Arlington, Virginia. Available http://www.natureserve.org/explorer. (Accessed: July 25, 2013).
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Figure 3. Distribution of Copperhead snakes (Agkistrodon contortrix) in the United States. Used with permission from NatureServe. 2013. NatureServe Explorer: An online encyclopedia of life [web application]. Version 7.1. NatureServe, Arlington, Virginia. Available http://www.natureserve.org/explorer. (Accessed: July 25, 2013). Figure 4. Distribution of Cottonmouth snakes (Agkistrodon piscivorus). Used with permission from NatureServe. 2013. NatureServe Explorer: An online encyclopedia of life [web application]. Version 7.1. NatureServe, Arlington, Virginia. Available http://www.natureserve.org/explorer. (Accessed: July 25, 2013).
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Description Minor injury Puncture marks only Moderate injury Puncture marks Cellulitis or ecchymosis localized to puncture marks Level 2 Findings +Spreading erythema, induration, or purulent material -Necrosis Level 3 Findings +Tissue necrosis *Systemic symptoms (neurologic, cardiovascular, gastrointestinal) irrespective of local findings.
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Wound Class 1
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Type of Snake
4%
4%
0.83
4% 4% 6%
4% 1% 3%
42%
43%
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83%
81%
0.83
9% 33% 48% 10% 18%
10% 37% 44% 10% 17%
9% 31% 50% 10% 18%
0.94
80%
81%
79%
0.84
2 days Range 1-7
2 (range 1-5)
1 (range 1-7)
0.07
65 6 6 3 6
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Signs of envenomation 1 WSS 2 3 4 Coagulopath y Admitted to Hospital Median Length of Hospital stay (admitted patients) WSS: wound severity score
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42% 58% 64% 35% 1% 40%
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p-value
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Water moccasins Rattlesnakes Coral Snake Other identified (venomous) snake Unidentified snake
Did not receive CroFab (n=103) 30% 70% 58% 41% 2% 44%
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Site of Bite
Female Male Leg Arm Other Copperhead
Received CroFab (n=48)
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Gender
Total population (n=151) Number (%) 52 (34%) 99 (66%) 91 57
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Variable
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Table 2: Demographic, clinical, and laboratory characteristics of the study population
0.15 0.67
1.0
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14%
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0% 14% 45%
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7%
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93% 9/64 (14.1%) 1.4%
4 (n=14) 85% 0% 100% 5/14 (35.7%) 0%
28%
50%
1/20 (5%) 54% 90%
0% 71% 80%
37% 0%
32% 0%
36% 4/15 (27%)
10%
22%
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0% 39% 74%
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36% 0%
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86% 8/43 (18.6%) 4%
3 (n=72) 89% 0%
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71% 1/10 (10%) 0%
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Intervention CBC Thrombocytopenic (
