Comparing cost of F(.ab')2AV vs FabAV in the treatment of copperhead envenomation-One center's experience.

The definitive treatment of North American crotalid snakebites is antivenin. In 2000, an FabAV antivenom (CroFab®) was introduced and in 2022, F(ab')2AV (Anavip®) was approved for treatment of copperhead bites. Our center that sees primarily copperhead snake bites added the recently approved treatment as a second option for the 2022 snake bite season. This brief report we describe our initial experience with the two antivenins via retrospective chart review: the cost, charge, laboratory differences, response to therapy, complications and duration of hospitalization of admitted patients with copperhead envenomation. Using three independent reviewers in this IRB exempt report we found 31 patients with copperhead bites (7 exclusions) leaving 19 adults and 7 children for analysis. We found there was no difference in age, sex, presence of lab abnormalities, total vials administered, or length of stay. There was significant differences in hospital costs and charges to the patient. Future research should include multi-center experiences comparing the two antivenins.

Efficacy of methylene blue in a murine model of amlodipine overdose.

INTRODUCTION: Amlodipine overdoses have significant cardiac toxicity and are difficult to treat. Methylene blue has potential as a treatment for overdoses. METHODS: A randomized controlled study of methylene blue as a treatment for amlodipine toxicity was conducted in C57Bl/6 mice. A baseline echocardiography was followed by gavage administration of amlodipine (90 mg/kg). Five minutes after gavage, animals received either vehicle solution (controls) or methylene blue (20 mg/kg) by intra-peritoneal injection. Animals were continuously monitored, and cardiac parameters were acquired every 15 min up to two hours. RESULTS: Only 50% of control animals survived to the two-hour endpoint compared to 83% that received methylene blue. Amlodipine delivery induced significant reduction in left ventricular ejection fraction (EF), fractional shortening (FS), stroke volume (SV), and cardiac output (CO) in the vehicle treated animals relative to animals in the treatment group (p < 0.05 vehicle versus Methylene blue for EF, FS, SV, CO, and HR). DISCUSSION: The amlodipine dose induced cardiotoxicity that were effects were more pronounced in the untreated group. 50% vehicle controls quickly progressed into heart failure (within 90 min of exposure) and did not survive the two h observation endpoint. Distinctly, only one animal from the Methylene blue treatment group did not survive (83% survival) the study. Additionally, the surviving animals from the Methylene blue group displayed significantly higher ejection fraction, fractional shortening, stroke volume, and cardiac output compared to vehicle group, indicating that methylene blue preserved cardiac function. CONCLUSION: In this mouse model of amlodipine overdose, methylene blue decreased cardiac toxicity.

Wernicke encephalopathy associated with hyperemesis gravidarum.

Emergency physicians frequently treat hyperemesis gravidarum and should be aware of possible complications. Wernicke encephalopathy secondary to thiamine deficiency should be considered in the differential diagnosis of acute encephalopathy in pregnant women. A seventeen-week pregnant 27-year-old woman presented to the Emergency Department with nausea, emesis, and right upper quadrant abdominal pain. Ultrasound diagnosed gallbladder sludge. Surgical consultant offered cholecystectomy versus expectant management. She improved with IV hydration, ondansetron, and was discharged on hospital day 3 with a diagnosis of hyperemesis gravidarum and gallbladder sludge. Three days later she presented with continued emesis and altered mental status. She and family members denied alcohol or illicit drug use. Vital signs were pulse 99/min, blood pressure 115/70, temperature 36.4 °C, respiratory rate 18, and oxygen saturation 99%. Neurological examination was delirium, variable mentation, and inability to follow commands. She had internuclear opthalmoplegia with bilateral nystagmus. CT scan of brain was negative. MRI found abnormal T2-weighted signal in the central pons and medial thalami. Radiographic differential included central pontine myelinolysis, dysmyelinating conditions from malnutrition, toxic encephalopathy, and Wernicke encephalopathy. Thiamine level was below the limits of detection. Alcohol and urine drug screen were negative. Diagnosis was thiamine deficiency secondary to hyperemesis gravidarum with Wernicke encephalopathy. Emergency physicians frequently treat hyperemesis gravidarum. Nutritional status should be evaluated in patients who are unable to take neonatal vitamins. Awareness should exist of possible complications, including Wernicke encephalopathy secondary to thiamine deficiency.

Long-term efficacy of pressure immobilization bandages in a porcine model of coral snake envenomation.

BACKGROUND: Pressure immobilization bandages delay mortality for 8 hours after coral snake envenomation, but long-term efficacy has not been established. OBJECTIVE: The objective of this study is to determine the long-term efficacy of pressure immobilization bandages after coral snake envenomation in the absence of antivenom therapy. METHODS: A randomized, observational pilot study was conducted. Ten pigs (17.3-25.6 kg) were sedated, intubated for 5 hours, and injected subcutaneously with 10 mg of lyophilized Micrurus fulvius venom resuspended in water. Pigs were randomly assigned to a control group (no treatment) or a treatment group (compression bandage and splint) approximately 1 minute after envenomation. Bandage pressure was not controlled. Pigs were monitored daily for 21 days for signs of respiratory depression, decreased oxygen saturations, and paralysis. In case of respiratory depression, pigs were humanely euthanized and time to death recorded. Statistical analysis was performed with Fisher exact test, Mann-Whitney U test, and Kaplan-Meier survival curve as appropriate. RESULTS: Median survival time of control animals was 307 minutes compared with 1172 minutes in treated animals (P = .10). Sixty percent of pigs in the treatment group survived to 24 hours vs 0% of control pigs (P = .08). Two of the treatment pigs survived to the end point of 21 days but showed necrosis of the distal lower extremity. CONCLUSIONS: Long-term survival after coral snake envenomation is possible in the absence of antivenom with the use of pressure immobilization bandages. The applied pressure of the bandage is critical to allowing survival without necrosis. Future studies should be designed to accurately monitor the pressures applied.

Naltrexone prevents delayed encephalopathy in rats poisoned with the sarin analogue diisopropylflurophosphate.

BACKGROUND: Acute poisoning with organophosphate compounds can cause chronic neuropsychological disabilities not prevented by standard antidotes of atropine and pralidoxime. We determine the efficacy of naltrexone in preventing delayed encephalopathy after poisoning with the sarin analogue diisofluorophosphate (DFP) in rats. METHODS: A randomized controlled experiment was conducted. Rats were randomly assigned to receive a single intraperitoneal (IP) injection of 5 mg/kg DFP (n = 12) or vehicle control (isopropyl alcohol, n = 5). Rats were observed for cholinesterase toxicity and treated with IP atropine (2 mg/kg) and pralidoxime (25 mg/kg) as needed. After resolution of acute toxicity, rats injected with DFP were again randomized to receive daily injections of naltrexone (5 mg/kg per day) or saline (vehicle control). Control animals also received daily injections of saline. For 4 weeks after acute poisoning, rats underwent neurologic testing with the Morris Water Maze for assessment of spatial learning and reference memory. Comparisons on each test day were made across groups using analysis of variance followed by Fisher's least significant difference. Comparisons of changes in performance between first and last test day within each group were made using a paired t test. Significance was determined at P < .05. RESULTS: All rats receiving DFP developed toxicity requiring rescue. Spatial learning was significantly worse in the DFP-only group compared with the naltrexone-treated and control groups at day 10 (P = .0078), day 13 (P = .01), day 24 (P = .034), and day 31 (P = .03). No significant differences in reference memory were detected at any time point. CONCLUSION: Naltrexone protected against impairment of spatial learning from acute poisoning with DFP in rats.

Retrospective chart review of substance abuse in patients with psychiatric emergencies in an emerging urban county.

Objectives: Substance abuse is common in patients with psychiatric emergencies. To further understand the connection between substance abuse and psychiatric disorders, a retrospective chart review was done that included positive drug screens among patients with psychiatric emergencies and to determine whether there was an association between substances used and the psychiatric diagnosis. Methods: A retrospective chart review of patients seen in an emergency department with psychiatric emergencies was conducted. The review comprised 1000 charts with diagnoses of anxiety, depression, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, alcohol abuse, or schizoaffective disorder. Data collected included patient demographics, tobacco abuse, chief complaint, arrival mode, voluntary versus involuntary status, suicide attempt on presentation, psychiatric diagnoses, urine drug screen, and ethanol results. Chi-square statistical analysis was conducted to examine the relationship between substances of abuse and psychiatric diagnoses. Results: Approximately 58% of patients with a history of psychiatric illness had a positive urine drug screen. Of 245 patients with schizoaffective disorder, 69 (28%) were positive for tetrahydrocannabinol (THC) and 48 (20%) were positive for cocaine. Of 225 patients with depression, 59 (29%) were positive for THC and 33 (15%) were positive for cocaine. Cannabis was the most commonly reported substance used among patients with depression, schizophrenia, anxiety, schizoaffective disorder, and bipolar disorder, and ethanol was most common in patients with ADHD. No significant correlations were found between psychiatric diagnosis and positive drug screens. A statistically significant secondary end point was found that White people using cannabinoids were more likely to attempt suicide than were African American people (P = 0.02). Conclusions: Positive drug screens were common among patients presenting to an ED with psychiatric emergencies. Cannabis was the most commonly reported substance used among patients independent of diagnosis. Ethanol was the most common in patients with ADHD. Urine drug screens are unlikely to provide insights into relationships between specific substance use and psychiatric emergencies.

Trending of a falsely elevated serum creatinine after a pediatric nitromethane ingestion: A case report.

Introduction: Nitromethane is a primary nitroalkane used as a solvent and a fuel that may be toxic by ingestion, inhalation, or contact. Its presence can be detected in serum of exposed persons, but levels are not readily available to guide patient care. Nitromethane has been shown to falsely elevate serum creatinine when clinical laboratories use Jaffe assays to measure creatinine; enzymatic assays are not affected. Ex vivo experiments have demonstrated a linear relationship between serum nitromethane and the elevation in Jaffe assay creatinine. This case report demonstrates an elevation of creatinine measured by Jaffe assay with normal creatinine measurement by enzymatic assay after exposure to nitromethane. Case report: A 21-month-old girl ingested an unmeasured quantity of a hobby fuel, a fuel containing methanol, nitromethane (20%), and lubricants used in miniature internal combustion engines, such as remote-controlled cars. She was initially evaluated at a community hospital, treated empirically for methanol toxicity with fomepizole and folic acid, and transferred to a university hospital for further management. By 19 hours after ingestion, methanol was below detection, but a serum creatinine of 2.63 mg/dl raised concern for kidney injury. Toxicology consultation recognized that the creatinine had been measured using a Jaffe assay and recommended a repeat creatinine using an enzymatic assay, which was within normal limits. The patient remained an inpatient for further evaluation, which permitted trending of her Jaffe assay creatinine over a 3-day period. The Jaffe assay creatinine demonstrated a gradual decline; repeat enzymatic assay creatinine remained within normal limits. Discussion: The decline in this pediatric patient's Jaffe assay creatinine is consistent with first-order clearance of nitromethane, which has been previously described in adult exposures. This case demonstrates how Jaffe assay-derived serum creatinine may be useful in the pediatric population to establish, quantify, and trend nitromethane exposure with essential concurrent use of an enzymatic assay to determine actual creatinine.

Failure of Computed Tomography (CT) in Detecting an Aspirin Pharmacobezoar: A Case Report.

BACKGROUND Prior studies suggest CT can identify bezoars under certain circumstances. Endoscopy provides diagnostic and therapeutic benefit in the setting of suspected aspirin bezoar. Does the absence of findings on CT scan exclude the presence of an aspirin bezoar? CASE REPORT A 64-year-old woman called the police and stated she ingested a bottle of aspirin to harm herself. Upon arrival to the Emergency Department, she was tachypneic with a GCS of 15. Initial laboratory results were: salicylate level of 1143 mcg/mL, respiratory alkalosis, bicarbonate of 9 meq/L, anion gap of 23, and normal renal function. Initial therapeutic intervention included infusions of glucose and bicarbonate, multiple doses of activated charcoal, intubation, and emergent hemodialysis. After hemodialysis, the salicylate level rebounded, and a Gastroenterology (GI) consultation was requested to rule out bezoar. On day 2, GI requested an abdominal CT scan with Gastrografin in place of endoscopy due to hemodynamic instability. A CT scan was negative for bezoar. After multiple hemodialysis sessions and whole-bowel irrigation with rebounding salicylate levels, GI was consulted again for reevaluation for endoscopy. On day 5, an endoscopy discovered a concretion containing pill fragments. Another endoscopy performed on day 7 removed further fragments. Salicylate levels began to consistently decline. Unfortunately, the patient's neurologic status did not improve, and on day 11 she was switched to palliative care and died. CONCLUSIONS Endoscopy with direct visualization is diagnostic and therapeutic in the setting of a possible bezoar. The absence of pharmacobezoar on imaging should not delay endoscopy in a clinical setting suggesting bezoar.

A localizing circumferential compression device increases survival after coral snake envenomation to the torso of an animal model.

BACKGROUND: Pressure immobilization bandages have been shown to delay onset of systemic toxicity after Eastern coral snake (Micrurus fulvius) envenomation to the distal extremity. OBJECTIVES: To assess the efficacy of a novel compression device in delaying onset of systemic toxicity after truncal envenomations with Eastern coral snake (Micrurus fulvius) venom in a porcine model. METHODS: With University approval, nine juvenile pigs (11 kg to 22 kg) were sedated, anesthetized, and intubated but not paralyzed to ensure continuous spontaneous respirations in a university animal laboratory. Each animal was injected subcutaneously with 10 mg of M. fulvius venom in a pre-selected area of the trunk. After 1 min, six animals had the application of a novel, localizing circumferential compression (LoCC) device applied to the bite site (treatment group) and three animals had no treatment (control group). The device was composed of a rigid polymer clay form molded into a hollow fusiform shape with an internal dimension of 8 × 5 × 3 cm and an elastic belt wrapped around the animal securing the device in place. Vital signs were recorded at 30-min intervals. End points included a respiratory rate below 3 breaths/min, oxygen saturation < 80%, or survival to 8 h. Survival to 8 h was analyzed using Fisher's exact test, with p < 0.05 indicating significance. Survival analysis was performed using the Mantel-Cox test to assess time to death with outcomes represented in a Kaplan-Meier Cumulative survival plot. RESULTS: Five of the six pigs in the treatment group survived 8 h (293-480 min). None of the control pigs survived to 8 h (Fisher's exact p = 0.04), with mean time of respiratory failure 322 min (272-382 min). Survival analysis showed a significant delay in time to event in the treatment group compared to the control group (p = 0.04). CONCLUSIONS: The LoCC device used in this study delayed the onset of systemic toxicity and significantly increased survival time after artificial truncal envenomation by Eastern coral snake venom.

Epidemics of mold poisoning past and present.

Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

First Aid and Pre-Hospital Management of Venomous Snakebites.

BACKGROUND: Antivenom is the definitive treatment for venomous snakebites, but is expensive and not available in many rural and poorly developed regions. Timely transportation to facilities that stock and administer antivenom may not be available in rural areas with poorly developed emergency medical services. These factors have led to consideration of measures to delay onset of toxicity or alternatives to antivenom therapy. METHODS: PubMed searches were conducted for articles on snakebite treatment, or that contained first aid, emergency medical services, tourniquets, pressure immobilization bandages, suction devices, and lymphatic flow inhibitors. RESULTS: The reviewed articles describe how venoms spread after a venomous snakebite on an extremity, list the proposed first aid measures for delaying the spread of venoms, and evaluate the scientific studies that support or refute methods of snakebite first aid. The recommendations for field treatment of venomous snakebites will be discussed. CONCLUSIONS: The evidence suggests that pressure immobilization bandages and related strategies are the best interventions to delay onset of systemic toxicity from venomous snakebites but may increase local toxicity for venoms that destroy tissue at the site of the bite, so their use should be individualized to the circumstances and nature of the venom.

Heparin reverses anaphylactoid shock in a porcine model.

STUDY OBJECTIVE: Heparin binds histamine and has been advocated as a therapy for anaphylactic and anaphylactoid shock. The efficacy of heparin in treating anaphylactoid shock is compared with therapy with diphenhydramine and epinephrine, as well as sham treatment with saline. METHODS: This controlled study of 9 anesthetized, intubated pigs induced shock with intravenous calcium ionophore A23187 (5 mg/kg), which is known to degranulate mast cells in vitro. Serum histamine levels were measured using an enzyme-linked immunosorbent assay. Shock, defined as a greater than 20% decrease in mean arterial blood pressure, was treated with intravenous saline, epinephrine with diphenhydramine, or heparin. Data were analyzed using Wilcoxon rank sum and analysis of variance, as appropriate. RESULTS: All pigs developed anaphylactoid shock after injection with A23187, as evidenced by hypotension, flushing, and an increase in plasma histamine. Mean arterial blood pressure fell from a mean of 73 (SD 10) mm Hg to 28 (SD 16) mm Hg after injection (P<.001; 95% confidence interval [CI] of the difference in pressures 34 to 57 mm Hg). Mean serum histamine levels increased from 712 micromol/dL (SD 731) to 1,154 micromol/dL (SD 799) after injection (Z value -2.201; P=.0277; 95% CI of the difference -610 to -99). Both epinephrine with diphenhydramine and heparin but not saline reversed shock. CONCLUSION: A23187 induced anaphylactoid shock in all subjects. Therapy with intravenous epinephrine combined with diphenhydramine reversed shock. Heparin also rapidly reversed shock.

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment.

Veterans of Operation Desert Storm/Desert Shield - the 1991 Gulf War (GW) - are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25-32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities. Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out. This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008). We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called "toxic wounds" by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses.

Pressure-immobilization bandages delay toxicity in a porcine model of eastern coral snake (Micrurus fulvius fulvius) envenomation.

STUDY OBJECTIVES: Pressure-immobilization bandages are used in countries where neurotoxic snake envenomations are common. They impede lymphatic egress from the bite site and delay systemic venom toxicity. The effectiveness of these devices has not been evaluated in coral snake envenomations. We investigated the efficacy of pressure-immobilization bandages in delaying the onset of systemic toxicity in a porcine model of coral snake envenomation. METHODS: A randomized controlled trial of pressure-immobilization bandages was conducted in a university animal care center. Subjects were 12 anesthetized, spontaneously breathing pigs, ranging from 9.1 to 11.4 kg. After injection with 10 mg of Micrurus fulvius fulvius venom in the subcutaneous tissue of the distal foreleg, subjects were randomized to receive no treatment or application of a pressure-immobilization bandage at 1 minute after injection. Treated animals had elastic bandages applied to the extremity and splinting for immobilization. Vital signs and quality of respirations were recorded. Outcome was the onset of respiratory failure or survival to 8 hours. Necropsies and histologic analysis of the envenomation site was performed. RESULTS: One animal from each group was removed because of the discovery of pre-existing respiratory pathology. Four of 5 pigs in the treatment group survived to 8 hours, but none in the control group survived. Mean time to onset of respiratory compromise was 170.4 +/- 33.3 minutes in the control group. None of the pigs had histologic changes at the envenomation site consistent with ischemia or pressure-related injury. CONCLUSION: Pressure-immobilization bandages delayed the onset of systemic toxicity in our porcine model of M fulvius envenomation.

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime.

Humans and rats poisoned with sarin develop chronic neurological disabilities that are not prevented with standardized antidotal therapy. We hypothesized that rats poisoned with the sarin analogue diisopropylfluorophosphate (DFP) and resuscitated with atropine and pralidoxime would have long-term memory deficits that were preventable with naltrexone treatment. Long Evans rats (250-275 g) were randomized to: DFP (N = 8): single subcutaneous (SC) injection of DFP (5 mg/kg). Treatment (N = 9): DFP (5 mg/kg) followed by chronic naltrexone (5 mg/kg/day × 12 weeks). Control (N = 12): single SC injection of isopropyl alcohol, (DFP vehicle) followed by chronic naltrexone (5 mg/kg/day). If toxicity developed after injection, antidotal therapy was initiated with atropine (2 mg/kg) and pralidoxime (25 mg/kg) and repeated as needed. After 12 weeks, rats underwent testing for place learning (acquisition) across 5 days of training using the Morris Water Maze. On day 6 a memory retention test was performed. Statistical analysis was performed using IBM SPSS Statistics. Rats receiving DFP rapidly developed toxicity requiring antidotal rescue. No differences in acquisition were seen between the DFP vs. DFP + naltrexone rats. During memory testing, DFP-poisoned rats spent significantly less time (29.4 ± 2.11 versus 38.5 ± 2.5 s, p < 0.05) and traveled less distance (267 ± 24.6 versus 370 ± 27.5 cm, p < 0.05) in the target quadrant compared to the treatment group. Treatment rats performed as well as control rats (p > 0.05) on the test for memory retention. Poisoning with DFP induced impaired memory retention. Deficits were not prevented by acute rescue with atropine and pralidoxime. Chronic naltrexone treatment led to preserved memory after DFP poisoning.

Efficacy of Trypsin in Treating Coral Snake Envenomation in the Porcine Model.

Antivenom is the definitive treatment for venomous snakebites. Alternative treatments warrant investigation because antivenom is sometimes unavailable, expensive, and can have deleterious side effects. This study assesses the efficacy of trypsin to treat coral snake envenomation in an in vivo porcine model. A randomized, blinded study was conducted. Subjects were 13 pigs injected subcutaneously with 1 mL of eastern coral snake venom (10 mg/mL) in the right distal hind limb. After 1 min, subjects were randomized to have the envenomation site injected with either 1 mL of saline or 1 mL of trypsin (100 mg/mL) by a blinded investigator. Clinical endpoint was survival for 72 h or respiratory depression defined as respiratory rate <15 breaths per minute, falling pulse oximetry, or agonal respirations. Fisher's exact t test was used for between group comparisons. Average time to toxicity for the saline control was 263 min (191-305 min). The development of respiratory depression occurred more frequently in control pigs than treated pigs (p = 0.009). Four of the six pigs that received trypsin survived to the end of the 3-day study. No control pigs survived. Two of the trypsin treatment pigs died with times to toxicity of 718 and 971 min. Survival to 12 and 24 h was significantly greater in the trypsin treatment group (p = 0.002, p = 0.009, respectively). Local injection of trypsin, a proteolytic enzyme, at the site of envenomation decreased the toxicity of eastern coral snake venom and increased survival significantly. Further investigation is required before these results can be extended to human snakebites.

Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial.

BACKGROUND: Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. METHODS: We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. RESULTS: 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. CONCLUSIONS: In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Oral treatment of organophosphate poisoning in mice.

OBJECTIVE: Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition to supportive care. This study determined the efficacy of oral agents in preventing death from organophosphate poisoning. METHODS: The organophosphate paraoxon (8 mg/kg) was used in a murine model with lethality at four and 24 hours as an end point. For oral treatment, 15 male Balbc mice were given either atropine sulfate (4 mg/kg), or a combination of atropine sulfate (4 mg/kg) with pralidoxime (100 mg/kg), by oral gavage. A control group of 22 mice received water by oral gavage. Chi-square analysis was used to compare results in the different groups. RESULTS: Of the control group, six of 22 survived to four hours after paraoxon exposure. Of the exposed animals treated with oral atropine, eight of 15 survived to four hours. Of the exposed animals treated with a combination of atropine and pralidoxime, 13 of 15 survived to four hours. All animals surviving to four hours survived to 24 hours. The increased survival of animals in the atropine group relative to the control group was not significant (p = 0.09). Survival was significant in the group treated with atropine and pralidoxime relative to atropine alone (p = 0.02) and to the control group (p = 0.0002). All treated mice surviving at four hours were alive at 24 hours. CONCLUSIONS: Both oral atropine and a combination of oral atropine and pralidoxime improved survival, and combination therapy achieved statistical significance. Generalization of this result to other organophosphate pesticides, other doses of paraoxon, and other species cannot be made without further investigations.

A randomized controlled trial of trypsin to treat brown recluse spider bites in Guinea pigs.

Brown recluse spider bites result in necrotic skin lesions for which there is no known antidote. Since venom toxins are proteins, a proteolytic enzyme like trypsin might be effective in reducing toxicity. The aim of this study was to conduct a randomized controlled trial of trypsin to treat brown recluse spider bites in guinea pigs. Subjects were 18 female guinea pigs. Anesthesia for injections was inhaled isoflurane. Analgesia was 0.05 mg/kg of buprenorphine twice a day as needed. Intervention was intradermal injection of 30 µg of brown recluse venom (Spider Pharm, Yarnell, AZ). Immediately after envenomation, subjects were randomized to two groups of nine: trypsin 10 µg in 1 mL normal saline and 1 mL of normal saline. The primary outcome was lesion area over a 10-day time period. Statistical analysis was performed with repeated measures ANOVA. Mean lesion area was smaller but not statistically different in the placebo group. Maximum lesion size occurred at day 4 in both groups, when lesion area was 76.1 ± 108.2 mm(2) in the placebo group and 149.7 ± 127.3 mm(2) in the treatment group. P value was 0.15 for placebo vs. treatment. This study did not establish a role for trypsin as a treatment for brown recluse spider bites in a guinea pig model.