Characterizing Utilization and Outcomes of Digoxin Immune Fab for Digoxin Toxicity.

BACKGROUND: Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily. Digoxin immune fab (DIF) is an effective treatment for toxicity, however there are limited studies characterizing its impact on clinical outcomes in real-world clinical practice. OBJECTIVES: The aim of this study was to identify factors and healthcare outcomes associated with digoxin immune fab (DIF) treatment in patients with confirmed/suspected digoxin toxicity. METHODS: An IRB-approved retrospective chart review of digoxin toxic patients (2011-2020) presenting at an academic healthcare system was conducted. Demographic and clinical data were collected. Patients were stratified by DIF treatment versus non-DIF treatment. DIF utilization patterns (appropriate, use when not indicated, or underutilized) were determined using pre-defined criteria. Severe digoxin toxicity was defined as having one or more of the following: mental status disturbances, antiarrhythmic therapy, acute renal impairment or dehydration, serum digoxin concentration (SDC) > 4 ng/mL, or serum K+ > 5 mEq/mL. Logistic multivariable regression analysis evaluated factors associated with DIF use. All statistical analyses were performed in R version 4.1. RESULTS: Data from 96 patients (non-DIF treated group = 49; DIF treated group = 47) were analyzed. DIF was used appropriately in 70 patients (73%), underutilized in 19 (20%), and administered to 7 (7%) patients when it was not indicated. Several clinical parameters differentiated the DIF from the non-DIF group (p < 0.05) including higher mean SDC (3.41 ± 1.63 vs 2.87 ± 1.17), higher mean potassium (5.33 ± 1.48 vs 4.55 ± 0.87), more toxicity severity (85% vs 49%), and more likely to require cardiac pacing (26% vs 4%). Digoxin toxicity resolved sooner in the DIF group (coefficient - 0.702, 95% CI - 1.137 to - 0.267) (p < 0.01) and they had shorter intensive care unit lengths of stay (12.4 ± 20.3 vs 24.4 ± 28.7 days; p = 0.018). The all-cause mortality rate in patients appropriately managed with DIF therapy versus those patients where DIF was underutilized was 11% and 21%, respectively. CONCLUSIONS: Based on our study population, DIF therapy appears to be beneficial in limiting duration of toxicity and intensive care unit lengths of stay in digoxin toxic patients. Although DIF was appropriately utilized in most cases, there was a relatively high proportion of cases in which DIF treatment was either underutilized or not indicated.

Emergency department management of North American snake envenomations.

There are approximately 10,000 emergency department visits in the United States for snakebites every year, and one-third of those involve venomous species. Venomous North American indigenous snakes include species from the Crotalinae (pit vipers) and Elapidae (coral snakes) subfamilies. Treatment relies on supportive care, plus antivenom for select cases. While certain principles of management are widely accepted, controversies exist with regard to prehospital use of pressure immobilization, antivenom use, coagulation testing after copperhead envenomation, and fasciotomy. An evidence-based approach to management of North American venomous snakebites will be discussed, along with a review of the current controversies.

Harmful Algal Bloom Exposures Self-reported to Poison Centers in the United States, May-October 2019.

The National Poison Data System (NPDS) comprises self-reported information from people who call US poison center hotlines. NPDS data have proven to be important in identifying emerging public health threats. We used NPDS to examine records of people who had self-reported exposure to harmful algal blooms (HABs). Participating poison centers then contacted people who had called their centers from May through October 2019 about their HAB exposure to ask about exposure route, symptoms, health care follow-up, and awareness of possible risks of exposure. Of 55 callers who agreed to participate, 47 (85%) reported exposure to HABs while swimming or bathing in HAB-contaminated water. Nine callers reported health symptoms from being near waters contaminated with HABs, suggesting potential exposure via aerosolized toxins. Symptoms varied by the reported routes of exposure; the most commonly reported symptoms were gastrointestinal and respiratory. More public and health care provider education and outreach are needed to improve the understanding of HAB-related risks, to address ways to prevent HAB-related illnesses, and to describe appropriate support when exposures occur.

Pediatric guanfacine exposures reported to the National Poison Data System, 2000-2016.

Introduction: The purpose of this study was to characterize the frequency, reasons for exposure, clinical manifestations, treatments, duration of effects, and medical outcomes of pediatric guanfacine exposures reported to the National Poison Data System (NPDS) from 2000 to 2016.Methods: Data extracted from poison control center call records for pediatric (0-5 years, 6-12 years, and 13-19 years), single-substance guanfacine ingestions reported to NPDS between 2000 and 2016 was retrospectively analyzed.Results: A total of 10927 cases were identified for analysis. Pediatric single-substance guanfacine exposures reported to NPDS increased significantly during the study period, with a marked increase among 6-12-year-olds. The most commonly documented clinical effects across age groups were drowsiness (n = 4262, 39%), bradycardia (n = 1696, 15.5%), and hypotension (n = 1127, 10.3%). The duration of effect for most cases was >8 hours but ≤24 hours (n = 2395, 44.2%). The median documented quantity of guanfacine ingested was 0.11 mg/kg (range: 0.004-7.8 mg/kg). The difference between mg/kg ingested in no effect and minor effect groups compared to moderate and major effect groups was statistically significant in all three age groups.Conclusions: Pediatric guanfacine exposures reported to U.S. poison centers have increased significantly in the last fifteen years. The most common clinical findings secondary to guanfacine exposure were bradycardia, hypotension, and CNS depression. There was a statistically significant difference between the mg/kg of guanfacine ingested in the groups experiencing no effect or mild effect compared to moderate or major effects. However, the maximum ingested dose reported among 0-5-year-olds in the no effect group was 2.72 mg/kg, while the minimum dose eliciting a major effect in both 0-5 and 6-12-year-olds was 0.05 mg/kg. The overall incidence of major effects was very low, with the vast majority of patients experiencing minor symptoms or less. Based on this data, we agree with current recommendations that any symptomatic pediatric patient exposed to guanfacine should be observed in a health care facility for at least 24 hours.

Thromboelastography in the management of snakebite-induced coagulopathy: a case series and literature review.

: North American crotaline envenomations are a significant source of morbidity annually. Envenomation is marked by a constellation of effects that can include severe tissue damage, systemic effects such as anaphylaxis, and coagulopathy with bleeding. Traditionally, static plasma-derived tests such as protime and PTT are used to assess coagulation status. However, other tests are available that provide a whole blood assessment of all portions of coagulation including initiation, propagation, and clot maintenance. One such analytical test is TEG. Minimal data is available regarding the effect of snake venom on TEG results. We report on three cases of North American crotaline envenomation with subsequent TEG analysis. Our results show that TEG analysis does relate the same information as traditional monitoring parameters. Although only in an isolated case, the TEG analysis potentially revealed a fibrinolytic process prior to the same process being apparent with traditional monitoring. Future research is necessary to identify the role of TEG in crotaline snakebite management.

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.

Validation of a pre-existing formula to calculate the contribution of ethanol to the osmolar gap.

PURPOSE: The aim of this study was to validate the formula derived by Purssell et al. that relates blood ethanol concentration to the osmolar gap and determine the best coefficient for use in the formula. The osmolar gap is often used to help diagnose toxic alcohol poisoning when direct measurements are not available. METHODOLOGY: Part I of the study consisted of a retrospective review of 603 emergency department patients who had a concurrent ethanol, basic metabolic panel and a serum osmolality results available. Estimated osmolarity (excluding ethanol) was calculated using a standard formula. The osmolar gap was determined by subtracting estimated osmolarity from the actual osmolality measured by freezing point depression. The relationship between the osmolar gap and the measured ethanol concentration was assessed by linear regression analysis. In Part II of this study, predetermined amounts of ethanol were added to aliquots of plasma and the estimated and calculated osmolarities were subjected to linear regression analysis. RESULTS: In the cases of 603 patients included in Part I of the study, the median ethanol concentration in these patients was 166 mg/dL (Q1: 90, Q3: 254) and the range ethanol concentrations was 10-644 mg/dL. The mean serum osmolality was 338 mOsm/kg (SD: 30) and a range of 244-450 mOsm/kg. The mean osmolar gap was 47 (SD: 29) and a range of - 15 to 55. There was a significant proportional relationship between ethanol concentration and osmolar gap (r(2) = 0.9882). The slope of the linear regression line was 0.2498 (95% CI: 0.2472-0.2524). The slope of the linear regression line derived from the data in Part II of the study was 0.2445 (95% CI: 0.2410-0.2480). CONCLUSIONS: The results of our study are in fairly close agreement with previous studies that used smaller samples and suggest that an accurate conversion factor for estimating the contribution of ethanol to the osmolar gap is [Ethanol (mg/dL)]/4.0.

Refractory hypotension due to Rogaine® (minoxidil) ingestion managed with midodrine.

BACKGROUND: Minoxidil (Rogaine®) is a direct vasodilator that can cause significant toxicity when ingested. We report a case of ingestion of topical minoxidil [Rogaine® (Johnson & Johnson Healthcare Products, Division of McNeil-PPC, Inc)] resulting in refractory hypotension that was successfully managed with the oral α (1) agonist midodrine. CASE REPORT: A 48-year-old male who ingested an eight ounce bottle of Rogaine® presented to the emergency department. The patient presented with a blood pressure of 57/45 mmHg and a pulse of 84 beats per minute. The patient received IV fluids and multiple vasopressors to maintain an adequate mean arterial pressure. Midodrine, an oral α (1) vasopressor, was added 10 hours post ingestion and was able to maintain an adequate mean arterial pressure. Over the next two days, midodrine was titrated down as his blood pressure returned to baseline. CONCLUSION: Midodrine may serve as an additional option to treat toxicant induced hypotension.

Acute ethanol poisoning in a 6-year-old girl following ingestion of alcohol-based hand sanitizer at school.

BACKGROUND: Alcohol-based hand sanitizers (ABHSs) have been widely used in homes, workplaces and schools to prevent the spread of infectious diseases. We report a young child unintentionally ingested ABHS at a school, resulting in intoxication. METHODS: The child was a 6-year-old girl who had been brought to the emergency department (ED) for hypothermia, altered mental status (AMS), periods of hypoventilation, hypothermia and vomiting. Computed tomography of her head revealed nothing abnormal in intracranial pathology. Urine drug screening was negative. Alcohol level was 205 mg/dL on admission. Other abnormal values included potassium of 2.8 mEq/L, osmolality of 340 mOsm/kg and no hypoglycemia. Further investigation revealed that the patient had gone frequently to the class restroom for ingestion of unknown quantities of ABHSs during the day. The patient was admitted for one day for intravenous fluid hydration and close observation of her mental status. RESULTS: The patient was discharged from the hospital the next day without any complications. CONCLUSION: Despite the large safety margin of ABHSs, emergency physicians need to be aware of the potential risk of ingestion of a large amount of such products in children and consider it in the assessment and management of school-age children with acute AMS.

Diphenhydramine dose-response: a novel approach to determine triage thresholds.

CONTEXT: It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies have had conflicting results. Objective. We sought to evaluate DPH dose-response using a unique method that utilizes acetaminophen (APAP) serum concentrations to estimate DPH doses in patients ingesting APAP/DPH in a fixed-combination product. METHODS: We retrospectively analyzed APAP/DPH-only exposures in patients 2-80 years of age using case data from 15 U.S. poison centers. DPH dose was extrapolated from measured serum APAP concentrations. A clinically significant response (CSR) was predefined in terms of eight specific manifestations (e.g., coma) that would warrant emergency department intervention. Nominal logistic regression was used to model the probability of each recorded manifestation across DPH dose ranges examining fits for mg, mg/kg, log10 mg, and log10 mg/kg DPH doses. The threshold value where patients reliably became symptomatic was determined by further examining receiver operating characteristic curves. RESULTS: There were 509 cases that met inclusion criteria. Forty-five patients (9%) developed CSRs. A higher percentage of patients developed CSR at ≥ 7.5 mg/kg DPH and ≥1 g total DPH cutoff points (p < 0.05, Fisher's exact test). The best model for predicting the probability of CSR was a logistic fit of log(10) mg/kg dose (p < 0.05). By this model, for every 1 log(10) unit increase of mg/kg DPH dose, the odds of developing a CSR increased 47-fold (95% CI 17, 154). Receiver operating characteristic analyses showed a dose-related progression of symptoms. The cut-point with greatest sensitivity (98%) versus 1-specificity (57%) corresponded to an extrapolated mg/kg DPH dose of 8.2 mg/kg (95% CI 5.6, 10.5). CONCLUSION: Our findings support the current American Association of Poison Control Centers' guideline recommendation to refer patients to the hospital for evaluation if they have ingested greater than or equal to 7.5 mg/kg of DPH.

Toxicity from modafinil ingestion.

INTRODUCTION: Modafanil, a non-amphetamine stimulant, is used for narcolepsy, sleep apnea, and shift work sleep disorder. There is little available information on the toxicity of modafinil overdose. METHOD: We performed a retrospective multi-poison center chart review of patients from 11 states who had a single substance ingestion of modafanil with follow up to a known outcome for the years 2000-2007. Data collected included age, gender, dose ingested, clinical effects, length of hospital stay, and medical outcome. RESULTS: There were 137 patients, of whom 85 (63%) were female. Ages ranged from 1 to 82 years with a mean and median of 22 years (+18) and 20 years, respectively, with 43 patients (31%) aged <6 years. Most frequently reported clinical effects were tachycardia (n = 38), insomnia (n = 33), agitation (n = 27), dizziness (n = 25), and anxiety (n = 24). Forty-five patients were managed at home and 92 in a health-care setting, with only 23 (17%) requiring a medical admission. Therapies included benzodiazepines (n = 14), diphenhydramine (n = 5), beta-blockers (n = 3), haloperidol (n = 2), IV fluid hydration (n = 2), and one each of nitroglycerin, epinephrine, benztropine, and promethazine. CONCLUSIONS: In this case series, clinical effects of modafinil overdoses were generally mild with predominantly tachycardia and CNS toxicity. However, clinically significant effects warranting specific therapy occurred in a minority of patients.