Evaluation of the International Society on Thrombosis and Haemostasis definition of major bleeding in Arizona rattlesnake bites.

INTRODUCTION: In 2023, a group of experts proposed that a definition of major bleeding in pharmaceutically anticoagulated patients be used in all snakebite trials. This includes bleeding that results in death, is life-threatening, causes chronic sequelae, or consumes major healthcare resources, including bleeding into a major area or hemoglobin concentration decrease ≥20 g/L. We hypothesized that a decline in hemoglobin concentration ≥20 g/L is common but rarely clinically significant in our population of Arizona rattlesnake bite patients. METHODS: Poison center records of rattlesnake bites in humans from 2018 through 2022 were retrospectively reviewed and assessed for major bleeding by the above criteria. RESULTS: Four hundred and eighty-one patients met the inclusion criteria, of whom 265 (55.1%) had a hemoglobin concentration decrease ≥20 g/L. No patients died, and there was no evidence of bleeding into a critical organ. Three patients (1.1%) received blood transfusions. A decrease in hemoglobin concentration ≥20 g/L was 100% sensitive for identifying the major bleeding-associated outcomes; however, specificity was only 45.2%. Measures of healthcare utilization and chronic sequelae were somewhat higher in patients with a decrease in hemoglobin concentration ≥20 g/L. DISCUSSION: Laboratory manifestations of hemotoxicity were common in this population, but hemorrhage was rare. While over half of patients met the major bleeding criterion of a decline in hemoglobin concentration ≥20 g/L, only 1.1% had bleeding that was potentially life-threatening as measured by receipt of a red blood cell transfusion. None died or had bleeding into a critical area. While nonspecific for major bleeding, a drop in hemoglobin concentration correlated with worse envenomation severity: these patients received more vials of antivenom, had a higher medical bill, a longer hospital stay, and were less likely to report full recovery at 90 days. CONCLUSIONS: A decrease in hemoglobin concentration ≥20 g/L should not be used as evidence of major bleeding for Arizona rattlesnake envenomation studies, but it may have a role as an indirect marker of envenomation severity.

Infections following rattlesnake envenomation and use of antibiotics.

BACKGROUND: There are 7000-8000 venomous snake bites annually in the USA. Antibiotics are commonly administered to bite victims because infection is difficult to differentiate from local tissue injury following envenomation. METHODS: The Arizona Poison and Drug Information Center (APDIC) in Tucson oversees antivenom administration for 14 Arizona counties. Records (1999-2021) were searched for antibiotic use and confirmed infections after a rattlesnake bite. RESULTS: There were 4160 calls to APDIC regarding rattlesnakes. After excluding bites to animals, 'dry bites', prisoners and records with missing data, 2059 records were evaluated. Systemic antibiotics were administered to 206 patients (10% of bite victims). Twenty patients (0.97%) had confirmed infections, including cellulitis (n=10), fasciitis (n=4), abscess (n=3) and osteomyelitis (n=3). Five of the victims had positive blood cultures. The presence of tissue necrosis, leukocytosis, fever and elevated fibrinogen levels did not discriminate between toxic effects of venom and infection. CONCLUSIONS: Confirmed infections following a rattlesnake bite are uncommon (0.97% of bites). Physicians should refrain from prescribing antibiotics, as they are not justified for most rattlesnake bite victims and the variety of pathogens encountered precludes use of any single effective antibiotic.

Twenty-five years of suspected rattlesnake encounters in Arizona.

INTRODUCTION: Rattlesnake (Crotalus spp., Sistrurus spp.) bites in the southwestern United States are associated with significant morbidity. This study aims to describe 25 years of rattlesnake encounters reported to the Arizona Poison and Drug Information Center to identify vulnerable populations and circumstances where encounters occur to create public education to reduce future bites. METHODS: Cases of suspected rattlesnake encounters in Arizona reported to the Arizona Poison and Drug Information Center between 1999 and 2023 were analyzed to identify populations and circumstances associated with encounters. RESULTS: A total of 3,808 cases were analyzed overall and by age subgroups. Most encounters occurred in men (69.9%), during the evening (16:00-21:59; 49.2%), in summer (41.9%), and close to home (38.2%). Most bites occurred to the lower extremity (51%). Children 0 to 12-years-old have more encounters than those 13-years-old and older in rural zip codes (27.7% versus 14.8%; P = 0.005), during spring (31.8% versus 22.3%; P = 0.0005), and during the evening (64.4% versus 48.1%; P < 0.001). DISCUSSION: Rattlesnakes are encountered when rattlesnake and human behavior patterns overlap. Many people spend time outside during evening hours in the summer, and valuable resources like food, water, and shelter can be found near houses where humans spend much of their time. Most age groups have similar encounter circumstances but encounters among children 0 to 12-years-old differ in time of day, season, and urbanization level than encounters of those 13-years-old and older. Limitations of this study include underreporting of encounters, incomplete case details, potential reporting bias, potential snake misidentification, and geographic coverage of the poison center. CONCLUSION: Prevention of rattlesnake bites by reducing encounters is the most effective way to reduce suffering and healthcare costs. Future steps include creating and disseminating targeted public health education using the data collected.

A case report of mis-snaken identity: When misdiagnosis really bites.

When patients present with an unknown puncture wound, emergency physicians need to consider regional hazards, in addition to standard mechanical injury etiologies. In the Southwestern United States, one such hazard is the rattlesnake. In this report, we present a case in which a rattlesnake envenomation was not considered as a possible cause for a puncture wound of unknown origin, which resulted in an envenomation left untreated for 7 days. A full dry bite observation period of 12 h with serial physical exams and laboratory analysis with guidance from the region poison control center might have led to earlier recognition of an envenomation and antivenom administration. A male patient in his late 70's felt a painon his right ankle while in his backyard in southern Arizona. He did not see the cause and assumed he had sustained an insect bite. He went to the ED that day with minor pain and swelling and was discharged home. One week later, he re-presented severely anemic with edema and ecchymosis to the entire right lower extremity that developed over several days after his first ED visit. He was admitted for antivenom and blood transfusion and discharged on hospital day three. For as long as humans continue to interact with the natural world, venomous creature encounters are going to continue to happen. Rattlesnake envenomation should be included in a physician's differential diagnosis even if one is not witnessed, especially in regions with high rattlesnake activity. In addition to assessing for other potential causes of undifferentiated puncture wounds, serial physical examinations and laboratory testing (with guidance of the regional poison center) are necessary to rule out rattlesnake envenomation.

Neurotoxic respiratory failure absent following Arizona rattlesnake bites.

Warnings of neurotoxic respiratory paralysis following envenomation by rattlesnakes (Crotalus sp.) have been included in numerous scholarly publications over the past 60 years, resulting in fear and anxiety in the public and among clinicians. We examine the validity of the widespread belief that rattlesnakes in the arid southwestern United States, and particularly the Mohave Rattlesnake (Crotalus scutulatus), pose a significant risk of medically relevant respiratory weakness and paralysis in humans. A retrospective review of 3440 suspected rattlesnake bites reported to the Arizona Poison and Drug Information Center between 1999 and 2020 produced no evidence of respiratory weakness in a region with three species known to express significant amounts of neurotoxin in their venoms: Crotalus concolor, C. tigris, and the more widely distributed C. scutulatus. A literature review produced numerous warnings regarding respiratory paralysis following envenomation by rattlesnakes in our region that either lacked references or cited sources that did not contain strong supportive data. We found no case reports of neurotoxic respiratory weakness following Arizona rattlesnake bites in the literature and such reports in surrounding states were scant. We conclude that neurotoxic respiratory failure in this region following rattlesnake envenomation is extraordinarily rare. All rattlesnake bites should receive the same consideration and critical care, and warnings about significant risk of respiratory failure are unwarranted, regardless of species involved.

Fashionably late: A characterization of late coagulopathies in rattlesnake envenomations between Fab and F(ab')2 antivenoms.

BACKGROUND: Rattlesnake envenomation may lead to a multitude of clinical effects, including a late onset hemorrhage. Laboratory values such as platelets and fibrinogen are commonly used to assess the risk of developing a life-threatening bleed. To date, no specific threshold has been identified that links a lab value to the risk of bleeding. This has led to widespread practice variability among clinicians managing snake bites. In assessing risk for patients, we apply the concept that the more abnormal the lab values are, the higher the risk probably is. Late onset coagulopathies pose a unique clinical challenge because they indicate the potential risk for a life-threatening hemorrhage, yet they have been identified after hospital discharge. There are currently two antivenom (AV) products on the US market to treat rattlesnake envenomations, a Fab product, CroFab® (BTG, UK) and a F (ab')2 product, Anavip® (Bioclon, Mexico). OBJECTIVE: This study intended to characterize the incidence and severity of late coagulopathies reported to a Regional Poison Center (RPC) and hypothesized that late coagulopathies occur at rates higher than previously reported in the literature. Additionally, we sought to compare rates of late coagulopathy between Fab and F (ab')2 AV. METHODS: The investigators performed an in-depth review of all suspected snakebite envenomations from 2018 to 2020 that presented to an Arizona healthcare facility in the RPC's catchment area between January 2018 through December of 2020. Patients were excluded from analysis if they did not receive any antivenom, had an incomplete medical record with the APDIC, were diagnosed as something other than a rattlesnake bite or had a known medical history that clouded the diagnosis or assessment of a rattlesnake envenomation. RESULTS: In total, 522 records were reviewed of which 283 patients met the inclusion criteria. There were 149 patients who received Fab AV and 134 who received F (ab')2. No significant baseline or demographic differences existed between the groups. 95 of the 283 patients developed a late onset coagulopathy. 39% of the late onset coagulopathies were delayed, 32% were recurrent and 29% were persistent. When comparing the two different AV products, delayed or recurrent coagulopathies occurred in 36% of Fab AV- and 10% of F (ab')2 treated patients. Persistent coagulopathies occurred in 17% of Fab AV- and 8% of F (ab')2 treated patients. Interestingly, there were zero cases of late hypofibrinogenemia in any of the 134 F (ab')2 treated patients compared to 26% of all Fab treated ones. The average onset of late coagulopathy post-bite was 8 days for Fab AV and 7 for F (ab')2. CONCLUSION: The results from this study suggest the total rate of late onset coagulopathies may be underestimated. Additionally, our results suggest the potential that F (ab')2 AV may be associated with fewer late onset coagulopathies, especially late onset hypofibrinogenemia.

Mohave Rattlesnake (Crotalus scutulatus) Identification Revisited.

Crotalus scutulatus (Mohave rattlesnake) is a clinically significant pit viper broadly distributed across much of the arid southwestern United States and mainland Mexico. Identification of C scutulatus is a concern among emergency medical service and emergency department personnel owing to its reputation for severe envenomations and difficulty in visually differentiating between C scutulatus and other species, primarily Crotalus atrox (western diamond-backed rattlesnake). We contrast distinctive characteristics of C scutulatus, C atrox, and 3 other sympatric species: Crotalus molossus, Crotalus ornatus, and Crotalus viridis (western and eastern black-tailed rattlesnakes and prairie rattlesnake, respectively). Greenish coloration eliminates C atrox but does not confirm C scutulatus. Obvious coarse and fine speckling of the dorsal pattern and a pale postocular stripe intersecting the mouth characterize C atrox. Dorsal speckling is insignificant or absent in the other species, whereas the pale postocular stripe passes above the mouth in C scutulatus and C viridis and is absent in C molossus and C ornatus. Tails boldly ringed with alternating black and white or contrasting shades of gray are shared by C atrox and C scutulatus, respectively, but a lack of boldly ringed tails characterizes the other species. The proximal rattle segment is yellow and black, or entirely yellow, in C scutulatus but black in the others. The most reliable visual identifications are based on evaluations of multiple traits, all of which are variable to some extent. Traits such as tail ring width and the size and number of crown scales have frequently been overemphasized in the past.

Initial Experience with F(ab')2 Antivenom Compared with Fab Antivenom for Rattlesnake Envenomations Reported to a single poison center during 2019.

BACKGROUND: There are two Food and Drug Administration (FDA)-approved antivenoms available for rattlesnake envenomations in the United States: the equine-derived F (ab')2 product sold with the brand name Anavip (F (ab')2 AV) and the ovine-derived Fab product sold with the brand name Crofab (FabAV). OBJECTIVE: To compare the clinical outcomes of rattlesnake envenomation patients treated either with FabAV or F (ab')2AV or a combination of these. METHODS: This is a retrospective chart review of all human rattlesnake envenomations requiring antivenom reported to one regional poison control center in 2019. Patients were categorized as receiving F (ab')2 AV, FabAV, or a combination of both. Baseline characteristics included demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation. RESULTS: There were a total of 123 patients requiring antivenom. Of these, 57 (46.3%) received FabAV, 53 (43.1%) received F (ab')2 AV, and 13 (10.6%) received a combination of these. Those receiving F (ab')2 AV were younger, with an average age of 40.8 (±25.0) years versus 51.3 (±19.9) years (p = 0.0161) for those receiving FabAV. Time between envenomation and antivenom administration, ASSS, and the percentage of those with coagulopathy at presentation were otherwise similar. Patients treated with F (ab')2 AV or FabAV received a similar total number of vials [16.0 vials (±6.1) vs 14.5 vials (±5.4), p = 0.189], but patients treated with F (ab')2 AV were more frequently given additional doses [31 patients (58.5%) vs. 22 FabAV patients (38.6%), p = 0.0051]. In patients with outpatient follow-up for 2 weeks, fewer patients treated with F (ab')2 AV developed late coagulopathy [5 patients (11.1%) vs 22 FabAV patients (48.9%), p = 0.0004]. Adverse events were generally mild and uncommon with no difference in frequency between patients who received either antivenom (2 F (ab')2 AV patients vs 4 FabAV patients, p = 0.6637). CONCLUSIONS: Other than patient age, we found no significant difference in the baseline demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation between patients receiving F (ab')2 AV or FabAV. Patients receiving F (ab')2 AV were more likely to be given an additional dose beyond the minimum typical treatment course, but less likely to develop late coagulopathy. Adverse events were uncommon and generally mild whether patients received either antivenom.

Death by hand sanitizer: syndemic methanol poisoning in the age of COVID-19.

BACKGROUND: The advent of COVID-19 increased attention to hand hygiene in prevention of disease transmission. To meet the increased demand for hand sanitizer during the pandemic, the US FDA issued an Emergency Use Authorization allowing new manufacturers and importers to enter the market. Some of the newly introduced hand sanitizer products contained methanol in lieu of ethanol or isopropanol. We describe five patients with fatal methanol poisoning resulting from hand sanitizers improperly containing methanol. CASE SUMMARY: Comparing a 5-month period from 2019 to the same time frame in 2020, the Arizona Poison and Drug Information Center has seen an increase of 124% in exposures to hand sanitizer. Of these cases, 28% involved methanol-contaminated hand sanitizer. Five of these patients died from methanol poisoning. All five cases had similar clinical features with severe high anion gap metabolic acidosis and, in four patients, elevated osmolal gap. Methanol concentrations were consistently very elevated, but these results were not available before the patients succumbed. Four of the patients received fomepizole and adjunctive care. Two patients received emergency extracorporeal therapy. All five died despite maximal treatment efforts. CONCLUSION: During the pandemic in 2020, there was a proliferation of alcohol-based hand sanitizers which contained methanol. Exposure to these products, which failed to meet regulatory standards, led to increased harm and death. Challenges to treatment of methanol poisoning, especially in rural areas, include lack of access to timely laboratory measurement of methanol concentrations and lack of available emergency hemodialysis without transfer of the patient.