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Introduction Acetaminophen (paracetamol, APAP) poisoning is a prominent global cause of drug-induced liver injury. While N-acetylcysteine (NAC) is an effective antidote, it has therapeutic limitations in massive overdose or delayed presentation. The objective is to comprehensively review the literature on fomepizole as a potential adjunct antidote for acetaminophen toxicity. Methods A scoping review was performed using standardized search terms from inception through July 2021. Results Reports on fomepizole as a therapeutic adjunct for APAP toxicity span heterogeneous types of evidence. Eleven preclinical studies (in vitro and animal), fourteen case reports/series, and one human volunteer study were included. Fomepizole's action is mediated by inhibition of CYP2E1 to prevent oxidant stress generation, and inhibition of c-Jun N-terminal kinase (JNK) to decrease amplification of oxidant stress signaling to mitochondria. Studies have shown a reduction in oxidative metabolites likely by shunting metabolism away from CYP2E1 and a resultant decrease in liver injury in animals, independent of CYP2E1 interactions. Fomepizole has been linked to few adverse effects. Conclusion Based on in vitro and animal studies, and bolstered by case reports, fomepizole likely offers benefit as an adjunct antidote for APAP toxicity, however this remains to be shown in a human trial. NAC remains the standard of care antidote, but given that fomepizole is approved and generally safe, it may be considered for APAP toxicity as off-label use by experienced clinicians, in rare circumstances associated with increased risk of hepatotoxicity despite standard NAC dosing. The marginal clinical benefit of fomepizole adjunct therapy beyond NAC monotherapy remains to be clearly defined, and routine use for APAP overdose is premature based on current evidence.

Anavip (F(ab’)2AV) is a lyophilized F(ab’)2 immunoglobulin fragment derived from horses immunized with venom from Bothrops asper and Crotalus durissus. It was approved by the FDA in 2015 for treatm...

Utilization of marijuana as a medicinal agent is becoming increasingly popular, and so far, 25 states have legalized it for medical purposes. However, there is emerging evidence that marijuana use can result in cardiovascular side effects, such as rhythm abnormalities, syncope/dizziness, and myocardial infarction, among others. Further, there are currently no stringent national standards or approval processes, like Food and Drug Administration (FDA) evaluation, in place to assess medical marijuana products. This review includes the largest up-to-date pooled population of patients with exposure to marijuana and reported cardiovascular effects. Although purported as benign by many seeking to advance the use of marijuana as an adjunctive medical therapy across the country, marijuana is associated with its own set of cardiovascular risks and deserves further definitive study and the same level of scrutiny we apply in research of all other types of medications. When used as a medicinal agent, marijuana should be regarded accordingly, and both clinical providers and patients must be aware of potential adverse effects associated with its use for early recognition and management.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.

The aim of this study was to evaluate the blood levels of folic acid, vitamin B12, and 25-hydroxyvitamin D (25-OHD) in patients with lead poisoning compared with control subjects in Eastern Iran. This analytical case-control study was conducted on 40 lead-poisoned patients who were referred to Imam Reza Hospital in Birjand from 2018 to 2019. Blood samples were collected from an additional 40 individuals without lead poisoning as a control group. The results indicated that the mean vitamin B12, vitamin D, and folic acid levels for the case group were 356.5 ± 200.1 pg/ml, 24.38 ± 9.5 ng/ml, and 7.4 ± 3.7 ng/ml, respectively. Mean folic acid level in the case group was significantly lower than control group (7.4 ng/ml vs. 12.70 pg/ml, P = 0.001), whereas the mean of the vitamin D levels at the case group was significantly higher than that of the control group (24.3 ng/ml vs. 20.1 ng/ml, P = 0.03). Moreover, mean vitamin B12 levels were significantly lower in the case group in comparison with the control group (356.5 pg/ml vs. 500.8 pg/ml) (P

Abrin is a toxin of public health concern due to its lethality, lack of antidote, and potential for use as a bioterrorism agent. Possible routes of exposure include ingestion, inhalation, and injection. Onset of symptoms is often delayed, even in severe cases. In fatal cases, death occurs from multi-organ failure. We describe the clinical course, laboratory, and pathologic findings in a case of fatal human poisoning associated with abrin injection. The Abrus precatorius seeds in this case were obtained via the internet. The Centers for Disease Control and Prevention's Laboratory Response Network detected abrine in the urine confirming abrin exposure in this fatal poisoning.

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.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.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.

The Na+/K+-ATPase pump plays an essential role in the membrane potential. This pump is electrogenic as it transports three sodium ions out of the cell for every two potassium ions entering the cell...

Studies comprehensively summarizing the impact of tramadol use on glucose homeostasis are very sparse. Thus, the present study was performed to collect and summarize the latest information about this issue in a systematic way.An exhaustive literature search was carried out using relevant keywords. Web of Sciences, PubMed, Scopus, and Google scholar were interrogated until 30 June 2019. Case-control, cohort, cross-sectional, clinical trial, case report, and animal studies that focused on the objective of the study were retrieved. This review summarizes the results of 761 papers on glycemic changes due to tramadol exposure. Thirty-six publications reported hypoglycemia and 17 hyperglycemia during tramadol use. Twenty-two studies either reported normal blood glucose concentrations, or did not observe any difference in the blood glucose levels following tramadol use. Finally, hypoglycemia was reported in diabetic individuals exposed to tramadol in 12 studies.The data suggest that primarily hypoglycemia but some degree of hyperglycemia has been reported with tramadol use. Importantly, all studies on tramadol use in diabetes reported hypoglycemia. Tramadol-induced hypoglycemia may be severe in some cases. The risk of alterations in glucose homeostasis accompanying tramadol exposure indicates time importance of careful blood glucose monitoring during tramadol use.

This case report describes the effects of an envenomation from one of the most infrequently encountered species of rattlesnake in the United States, Crotalus willardi willardi (C. w. willardi), the Arizona Ridge-nosed Rattlesnake. A previously healthy 57-year-old male sustained a bite to his non-dominant hand from a C. w. willardi. The most pronounced effect from the envenomation was edema and progression of edema that extended from his hand to the mid bicep. He also experienced erythema and tenderness to palpation in the affected limb, and some diminished range of motion in the hand. He expressed only minimal pain. Other than a mildly positive D-Dimer and leukocytosis, he had no significant hematologic effects and no systemic effects. He was treated with standard doses of Crotalidae Polyvalent Immune Fab (Ovine). He reported complete recovery from the envenomation within three days of the bite. Although envenomation from rattlesnakes is somewhat common in Arizona, knowing the exact species of snake is not. Confirmed documentation is exceedingly rare as most people do not recognize the different rattlesnake species. In addition, some species of rattlesnake (such as C. w. willardi) are especially reclusive and found only in isolated mountainous regions. Being able to confirm an envenomation by C. w. willardi would require not only someone knowledgeable in herpetology, but also, preferably, photographic evidence. This case has both.

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management.

What is known and objective The interaction between valproic acid (VPA) and carbapenem antibiotics is well described with previous reports suggesting a reduction in VPA half-life between 47% and 90%. As described in this case, this interaction might be beneficial in the setting of toxic VPA ingestion. Case description An intubated, unresponsive patient arrived via emergency medical services after toxic VPA ingestion. Meropenem was prescribed for a suspected pneumonia and to take advantage of the VPA interaction. We observed a 56% decline in half-life with short-term meropenem dosing and an improvement in mental status shortly after administration. What is new and conclusion Our findings suggest a potential role for short-term carbapenem therapy for VPA overdose.

Background Behavioral health (BH)-related visits to the emergency department (ED) by older adults are increasing. This population has unique challenges to providing quality, timely care. Objective To characterize older adults with BH-related ED visits and determine risk factors associated with prolonged length of stay (LOS) and adverse events (AEs). Methods We performed a retrospective electronic health record review of all patients ≥65 years who presented to our ED from September 2011 to August 2012 for BH-related complaints. Sociodemographic, clinical, and utilization data were tested for association with LOS and AE. Results The 213 elder BH patients represented 4% of the 5267 total elder visits during the study period. Median age was 75 (interquartile range [IQR] 70−82); largely white (84.5%), female (58.7%), and non-Hispanic (69.5%). There was a median of two comorbidities (IQR 1−3), and 46.9% were cognitively impaired. Most (71.5%) were being evaluated on an involuntary basis. Median LOS was 16.2 h (IQR 9.7−29.7). Increased LOS was associated with involuntary status (12.4 h, 95% confidence interval [95% CI] 6.4−18.4); use of restraints (11.9 h, 95% CI 5.7−18.2); and failed discharge (28.8 h, 95% CI 21.2−36.6). For every 10 additional hours in the ED, the risk for an AEs (p = .002) or potential AEs (p = .01) increased 20%. Conclusion Elderly ED patients with BH complaints had high rates of cognitive impairment and multiple comorbidities. LOS was prolonged, and there were multiple contributing factors including involuntary status, chemical or physical restraint, and failed discharge. Patients with longer LOS were at increased risk of an AE or potentially AEs.

A 17-month-old child presented with hypertension, fussiness, constipation, and arthralgia due to mercury toxicity from a skin-lightening cosmetic used by her mother and grandmother. Blood mercury level was 26 mcg/L and urine level was 243 mcg/g creatinine. She was chelated with succimer. The home was contaminated and needed remediation.

Context Methamphetamine (MA) toxicity is a major health concern causing agitation, hyperkinesia, hyperthermia, and even death, affecting 24.7 million people worldwide. It has been observed that MA generates movement disorders in children similar to that of scorpion envenomation. Four cases have been reported where MA intoxication in children were both subjectively and objectively improved as indicated by the reversal of nystagmus and movement disorders following administration of Centruroides antivenom (AV) therapy. Objective Here, we aimed to demonstrate the reversal of MA induced movement disorders and hyperthermia by scorpion AV equine immune F(ab')2 in rats. Materials and methods Baseline core temperature and locomotor activity in adult male Sprague-Dawley rats (200-220 g) were evaluated prior to acute administration of AV (20 mg/kg, intraperitoneally, i.p.) + MA (10 mg/kg, i.p.) or control. Core body temperature was reassessed 10, 50, and 80 min post injection while locomotor activity was reassessed 20-35 and 60-75 min post injection. Results At 20-35 min, Saline + MA and BSA + MA groups showed a significant increase in the number of fine events compared to their respective control groups Saline + Saline and BSA + Saline, which indicates an increase in paw movements of animals in situ (p = 0.008, p = 0.006, respectively). In contrast, AV + MA demonstrated a non-significant increase in fine activity compared to the control group AV + Saline). At 60-75 min, the AV + MA treatment group were less likely to engage in locomotor activity indicated by the significant decrease in exploratory events compared to BSA + MA control group (p = 0.041). No significant percent change in core body temperature was observed in the AV + MA treatment group compared to the control groups, AV + Saline and BSA + MA. Discussion Here, we provide evidence for some aspects of MA-induced hyperkinesia but not hyperthermia reversed by scorpion AV. Further preclinical studies involving adolescent rodents may be necessary to completely mimic the reversal of MA toxicity seen in children in the clinic.

The authors present a case report of a 17-month-old female child who ingested a large amount of methamphetamine that looked very similar clinically to a scorpion envenomation specific to the southwestern United States by the speciesCentruroides sculpturatus. The child was initially treated with 3 vials of antivenom specific for that scorpion species and showed a transient, though clinically relevant neurologic improvement. Her clinical course of sympathomimetic toxicity resumed and she was treated with intravenous fluids and benzodiazepines after blood analysis showed significant levels of d-methamphetamine. This case report is to specifically underline the clinical confusion in discerning between these two conditions and the realization of limited and/or expensive resources that may be used in the process.

ACADEMIC EMERGENCY MEDICINE 2010; 17:824–833 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives: The objective was to evaluate the use of a payer-based electronic health record (P-EHR), which is a clinical summary of a patient’s medical and pharmacy claims history, in an emergency department (ED) on length of stay (LOS) and plan payments. Methods: A large urban ED partnered with the dominant health plan in the region and implemented P-EHR technology in September 2005 for widespread use for health plan members presenting to the ED. A retrospective observational study design was used to evaluate this previously implemented P-EHR. Health plan and electronic hospital data were used to identify 2,288 ED encounters. Encounters with P-EHR use (n = 779) were identified between September 1, 2005, and February 17, 2006; encounters from the same health plan (n = 1,509) between November 1, 2004, and March 31, 2005, were compared. Outcomes were ED LOS and plan payment for the ED encounter. Analyses evaluated the effect of using the P-EHR in the ED setting on study outcomes using multivariate regressions and the nonparametric bootstrap. Results: After covariate adjustment, among visits resulting in discharge (ED-only), P-EHR visits were 19 minutes shorter (95% confidence interval [CI] = 5 to 33 minutes) than non-P-EHR visits. Among visits resulting in hospitalization, the P-EHR was associated with an average 77-minute shorter ED LOS (95% CI = 28 to 126 minutes), compared to non–P-EHR visits. The P-EHR was associated with an average of $1,560 (95% CI = $43 to $2,910) lower total plan expenditures for hospitalized visits. No significant difference in total payments was observed among discharged visits. Conclusions: In the study ED, the P-EHR was associated with a significant reduction in ED LOS overall and was associated with lower plan payments for visits that resulted in hospitalization.

The only U.S. Food and Drug Administration-approved coral snake antivenom was officially discontinued in 2007, causing ever-diminishing supplies. This study describes the severity of U.S. coral snakebites during the last 25 years to determine trends in annual rates of these bites' medical outcomes.This study retrospectively analyzed all human coral snakebites voluntarily reported by the public and/or health care professionals to poison centers that were subsequently published in the Annual Reports of the American Association of Poison Control Centers (AAPCC) from 1983 through 2007. Annual rates of medical outcomes from coral snakebites were calculated by dividing the annual number of people bitten by coral snakes who developed fatal, major, moderate, minor, or no effect outcomes by the total annual number of people bitten by coral snakes. Negative binomial regression was used to examine trends in annual rates.From 1983 through 2007, the incidence rate of coral snakebites producing no effects significantly decreased by 4.7% per year [incidence rate ratio (IRR) = 0.953; 95% confidence interval (CI) = 0.920-0.987]. From 1985 through 2007, the incidence rates of minor and major outcomes did not significantly change; however, moderate outcomes significantly increased by 3.4% per year (IRR = 1.034; 95% CI = 1.004-1.064). No fatalities were reported from 1983 through 2007.Annual rates of coral snakebites producing no effects significantly decreased and those producing moderate outcomes significantly increased in our analyses of data from the last 25 years of published AAPCC Annual Reports. This study has important limitations that must be considered when interpreting these conclusions.

No study has focused on the nationwide epidemiology of severe and fatal rattlesnake bites during the last 25 years. We examined rates and temporal trends of severe and fatal rattlesnake bites across the United States. Our hypothesis was that nationwide annual rates of both severe and fatal outcomes from rattlesnake bites have remained unchanged over time.This study retrospectively analyzed all human rattlesnake bites published in the Annual Reports of the American Association of Poison Control Centers from 1983 through 2007. Annual rates of severe (major) and fatal rattlesnake bites were calculated using the annual number of major outcomes and fatalities as respective numerators and the total annual number of single rattlesnake bites (exposures) as denominators. Negative binomial and Poisson regressions were used to examine trends of severe and fatal rattlesnake bites over time.Annually, from 1985 to 2007, the incidence rate of major outcomes decreased by 2% per year (incidence rate ratio = 0.980; CI = 0.967-0.993), corresponding to an absolute annual rate decrease of two major outcomes per 1,000 bites per year. Annual rates of fatalities showed no statistically significant change from 1983 through 2007.This is the first study to examine rates and trends of published severe and fatal rattlesnake bites across the United States over the past 25 years. Annual rates of severe rattlesnake bites, derived from the published Annual Reports of the American Association of Poison Control Centers, have significantly decreased over time, whereas rates of fatal rattlesnake bites have remained unchanged.

Introduction Hazmat emergency preparedness is critical, especially as Hong Kong prepares for major international events, such as the 2008 Olympic Equestrian Games. No published medical study has described the identities and quantities of dangerous goods (DG) in the Kowloon area and listed what antidotes are needed for these DG. This study describes what hazardous materials are most common in Kowloon to prioritise emergency preparedness and training. Materials & methods Design A descriptive, cross-sectional study. Setting The Hong Kong Special Administrative Region, specifically Kowloon. Sample The Hong Kong Fire Services Department (HKFSD) Dangerous Goods Database (DGD). Interventions Descriptive statistical analyses with Stata 9.2. Chief outcome Identifying and quantifying dangerous goods in the HKFSD DGD. Results Most DG do not have antidotes. The most common DG with recognised antidotes are carbon monoxide, methylene chloride, fluorine, fluorides, fluoroboric acid, cyanides, nitriles, methanol, nitrobenzene, nitrites, and nitrates. The most common categories of DG are substances giving off inflammable vapours, compressed gases, and corrosive and poisonous substances. Conclusions Hazmat emergency preparedness and training should emphasize these most common categories of DG. Disaster planning should ensure adequate antidotes for DG with recognised antidotes, i.e., oxygen for carbon monoxide and methylene chloride; calcium gluconate or calcium chloride for fluorine, fluorides, and fluoroboric acid; hydroxocobalamin for cyanides and nitriles; ethanol for methanol; and methylene blue for methaemoglobinaemia produced by nitrobenzene, nitrites, and nitrates. Supportive care is essential for patients exposed to hazardous materials because most dangerous goods do not have antidotes.

We recently reported on a breastfed infant who succumbed to opioid toxicity following exposure to morphine, the active metabolite of codeine, which was prescribed to his mother who was a cytochrome P450 2D6 (CYP2D6) ultrarapid metabolizer. This report is believed to be the first case of neonatal fatality as a direct result of maternal drug excretion into breast milk and, therefore, it is critical to corroborate the causative relationship between maternal codeine use during breastfeeding and neonatal opioid toxicity with other existing evidence.To establish whether maternal use of codeine can be a cause of CNS depression in breastfed infants.A systematic review of the medical literature using several databases was conducted. The Naranjo Adverse Drug Reaction Probability Scale (NADRPS) was used to examine causality.In addition to our case report, three abstracts and two full-length studies reported adverse drug reactions (ADRs) in infants exposed to codeine in breast milk. In total, 35 infants were identified. Specifically, ADRs were described as unexplained episodes of drowsiness, apnea, bradycardia, and cyanosis in suckling infants. Using the NADRPS, codeine was found to be a definite cause of CNS depression in breastfed infants.The use of codeine by breastfeeding mothers can cause adverse CNS events in breastfed infants. Physicians should recognize codeine use during breastfeeding as a cause of CNS depression in infants, and breastfeeding mothers should be educated on these adverse events before receiving codeine.

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 effi cacy endpoint was coagulopathy (platelet count 150 K/mm 3 , fi brinogen 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.

The Gila monster (Heloderma suspectum) is a venomous lizard native to the deserts of southwestern United States (US) and northern Mexico. The purpose of this study was to describe human exposures to Gila monsters reported to US poison control centers (PCCs) with a focus on Arizona cases.The American Association of Poison Control Centers' National Poison Data System (NPDS) was used to access and retrospectively review all calls to US PCCs, concerning Gila monsters between January 1, 2000 and October 31, 2011. In addition, detailed records from the two Arizona PCCs were reviewed for the same time period.A total of 319 calls regarding Gila monsters were identified in the NPDS. Of these, 105 (33%) were human exposures; most (79%) occurred in males. A total of 71 (68%) of these 105 cases were referred to a health care facility (HCF); 30 (29%) were managed on-site. Of the 71 HCF referrals, 36 (51%) were discharged home and 17 (24%) were admitted. Most (65%) admissions were to an intensive care unit (ICU). Arizona's PCCs received 70 unique reports of Gila monster bite. Most (77%) of the bites in Arizona involved an upper extremity. Eight (11%) involved patients under the age of 18 years. Eleven (16%) Arizona cases were work-related. Twenty-eight (40%) of the 70 bites in Arizona were evaluated in a HCF, but not admitted. Eleven (16%) were admitted, of which five were to an ICU. Six patients had edema of airway structures; three required emergent airway management, one by cricothyrotomy. There were no deaths.Gila monster bites are uncommon. Many cases did not require hospitalization. Edema of airway structures is an infrequent, but life-threatening complication.

Dabigatran (Pradaxa) is a new oral anticoagulant approved by the Food and Drug Administration (FDA), available internationally and indicated as an alternative to warfarin for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Dabigatran does not require laboratory monitoring and its kinetics allow for a more rapid onset of action with a time to peak concentration of 1.25-1.5 h. We are reporting a fatality resulting from gastrointestinal bleeding after the ingestion of a single dose of dabigatran 150 mg.A 92-year-old man with a medical history of chronic obstructive pulmonary disease, hypothyroidism, and atrial flutter presented to the emergency department with complaints of weakness and rectal bleeding. He was seen by his Cardiologist the day before and was found to be in new atrial fibrillation. He was prescribed dabigatran 150 mg twice daily for anticoagulation therapy. He took one dose of dabigatran 150 mg at 2200 and woke up the following morning before 0900 with profuse rectal bleeding. The initial vital signs in the emergency department, approximately 11 h after ingestion, were heart rate 72 beats/min, blood pressure 62/30 mmHg, and lab work showed hemoglobin 9.9 g/dL, international normalization ratio (INR) 1.99, blood urea nitrogen (BUN) 66 mg/dL, and creatinine (SCr) 1.4 mg/dL (creatinine clearance (CrCl) 24.2 mL/min). He was resuscitated with intravenous fluids, two units of packed red blood cells, two units of fresh frozen plasma, platelets, and vitamin K 10 mg intravenously. He was also given an unknown dose of erythromycin early in his hospital stay. An actively bleeding gastric ulcer was discovered and treated with local epinephrine injections. Approximately 48 h after his exposure, he received an additional two units of blood to treat his decreasing blood pressure (98/41 mmHg). On day three, his hemoglobin and hematocrit were stable at 10 g/dL and 30%, INR 1.6, he was extubated and off vasoactive medications. Day six of hospitalization, he began having maroon stools, his hemoglobin decreased to 8.1 g/dL and his platelets to 81 × 1000/mcL. On day seven, the hemoglobin decreased to 6.4 mg/dL. Despite aggressive resuscitative efforts and supportive care, he died.This case demonstrates the potential of a single dose of dabigatran 150 mg to result in a fatal gastrointestinal hemorrhage. This patient was started on the maximum dose with a CrCl 33.9 mL/min and on admission CrCl 24.2 mL/min, suggesting underlying renal insufficiency.

OBJECTIVE: The goal of this study was to analyze trends in the annual rates of reported medical outcomes of cottonmouth (Agkistrodon piscivorus) snakebites in the United States, published in the annual reports of the American Association of Poison Control Centers in the course of 29 years. METHODS: This was a retrospective analysis of medical outcomes for cottonmouth snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by cottonmouths. Negative binomial regression was used to examine trends in annual rates. RESULTS: From 1985 through 2011, after controlling for the availability of CroFab, the annual incidence rate of cottonmouth snakebites causing no effect decreased significantly by 7.3%/year (incidence rate ratio [IRR] 0.927, 95% confidence interval [CI] 0.885-0.970), the incidence rate of minor outcomes did not change significantly (IRR 0.989, CI 0.974-1.006), the incidence rate of moderate outcomes increased significantly by 2.3%/year (IRR 1.023, CI 1.004-1.042), and the incidence rate of major outcomes did not change significantly (IRR 0.987, CI 0.935-1.041). One fatality was reported in 2011. CONCLUSIONS: Annual rates of cottonmouth snakebites producing no effects decreased significantly, those producing minor outcomes did not change significantly, those producing moderate outcomes increased significantly, and those producing major outcomes did not change significantly, from 1985 through 2011. Language: en

Introduction. 4-Aminopyridine (4-AP) is a potassium channel blocker used to increase muscle strength in the treatment of demyelinating diseases such as multiple sclerosis. We describe a case of ingestion by an 8-month-old child that resulted in severe but transient symptoms. Case Report. An 8-month-old boy was found with greenish saliva, and a capsule with green 4-AP powder was missing. On arrival to an emergency department, he was jittery, tachycardic, and tachypneic. Activated char- coal, a cathartic, and midazolam (0.5 mg/kg) were admin- istered before transfer to a tertiary pediatric hospital. On arrival, the infant remained tachycardic and tachypneic. His eyes deviated upward and he was noted to have 3 deep tendon reflexes bilaterally. He was administered 0.9% normal saline (20 mL/kg) for a wide pulse pressure with low diastolic blood pressure. The patient developed dramatic opisthotonic posturing and vermiform tongue fasciculations. The symptoms responded well to repeated intravenous doses of benzodiazepines. In this case, we used 2 doses of lorazepam (0.05 mg/kg each). During opisthotonic posturing, an electroencephalogram per- formed in the intensive care unit revealed no evidence of seizure activity. Within 20 hours after admission, the patient became asymptomatic. Conclusion. This case is, to our knowledge, the first documented pediatric 4-AP ingestion. Clinical signs and symptoms are described as well as the response to ther- apy with benzodiazepines. The electroencephalogram performed while the patient was symptomatic was neg- ative for seizures. Pediatrics 2003;111:e82-e84. URL: http: //www.pediatrics.org/cgi/content/full/111/1/e82; opistho- tonus, 4-aminopyridine, 4-AP, toxicology.

OBJECTIVE: The goal of this study was to analyze trends in the annual rates of reported medical outcomes of US copperhead (Agkistrodon contortrix) snakebites published in the annual reports of the American Association of Poison Control Centers in the course of 26 years. METHODS: This was a retrospective analysis of medical outcomes for copperhead snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by copperheads. Poisson and negative binomial regression were used to examine trends in annual rates. RESULTS: From 1983 through 2008, the incidence rate of copperhead snakebites causing no effect significantly decreased by 12.1%/year (incidence rate ratio [IRR] 0.879; 95% confidence interval [CI] 0.848-0.911]. From 1985 through 2008, the incidence rate of minor outcomes significantly decreased by 2.3%/year (IRR 0.977; 95% CI 0.972-0.981), whereas the rate of moderate outcomes significantly increased by 2.8%/year (IRR 1.028; 95% CI 1.024-1.033). The rate of major outcomes did not significantly change. One fatality was reported in 2001. CONCLUSIONS: Annual rates of copperhead snakebites producing no effects and minor outcomes significantly decreased, those producing moderate outcomes significantly increased, and those producing major outcomes did not significantly change in a 26-year period. Language: en

Background Emergency Department (ED) overcrowding is a national problem. Initiating orders in triage has been shown to decrease length of stay (LOS), however, nurse, physician assistant, and attending physician advanced triage have all been criticized. Study Objectives Our primary objective was to show that Emergency Medicine resident-initiated advanced triage shortens patient LOS. Our secondary objective was to evaluate whether or not resident triage decreases the number of patients who left prior to medical screening (LPTMS). Methods This prospective interventional study was performed in a 42-bed, Level III trauma center, academic ED in the United States, with an annual census of approximately 41,000 patients. A junior or senior Emergency Medicine resident initiated orders on 16 weekdays for 6 h daily on patients presenting to triage. Patients evaluated during the 6-h period on other weekdays served as the control. The study was powered to detect a reduction in LOS of 45 min. Multivariable median regression was used to compare length of stay and Fisher's exact test to compare proportions. Results There were 1346 patients evaluated in the ED during the intervention time. Regression analysis showed a 37-min decrease in median LOS for patients on intervention days as compared to control days ( p = 0.02). The proportion of patients who LPTMS was not statistically different ( p = 0.7) for intervention days (96/1346, 7.13%) compared to control days (136/1810, 7.51%). Conclusions Resident-initiated advanced triage is an effective method to decrease patient LOS, however, our effect size is smaller than predicted and did not significantly affect the percent of patients leaving before medical screening.

In the past 3 decades, lead levels in North American children have been declining. Despite the decline in lead exposure, lead toxicity remains a significant childhood environmental health hazard. The usual route of lead exposure is through ingestion, but lead toxicity secondary to retained bullet fragments has been well documented in the adult literature. The diagnosis of lead toxicity is often difficult and delayed secondary to vague and transient symptoms. Recognizing high-risk characteristics of bullet fragments can improve clinician awareness to the possibility of lead toxicity. The primary management of patients with continued lead exposure is to remove the source of exposure. However, in the case of retained bullet fragments, initiation of chelation therapy before surgical removal may be essential in preventing systemic toxicity. We present the case of a 14-year-old female with lead toxicity who presented with an 18-month course of chronic abdominal pain, vomiting, and anorexia 2 years after sustaining a gunshot wound to the right leg. The patient was treated with oral succimer and operative removal of bullet fragments.

BACKGROUNDInappropriate medication use in patients with heart failure (HF) presents challenges in providing optimal, evidence-based care.OBJECTIVETo evaluate the incremental differences of concurrent and persistent use of angiotensin-converting enzyme (ACE) inhibitors, β-blockers, loop diuretics, and digoxin on the one-year, all-cause risk of hospitalization and total healthcare costs associated with treatment of HF in patients enrolled in a managed care organization within the US.METHODSA retrospective database analysis was conducted spanning from January 1, 1997, to December 31, 1999. Multivariate regression methods were used to examine the association between treatment regimens and hospitalizations or costs after controlling for patient demographics and risk factors.RESULTSOf the 1903 patients meeting inclusion criteria, 32.3% (n = 615) received none of the 4 HF agents studied and were associated with a 2.5 times greater risk (p ≤ 0.001) of hospitalization and 43.6% higher (p ≤ 0.001) total costs compared with all other patients with HF. Comparatively, 13.9% (n = 264) utilized the HF medications investigated for at least 6 months. Of those with persistent use of ≥3 agents, approximate decreases in hospitalizations were noted of 80% (p ≤ 0.001) and total costs of 70% (p ≤ 0.001) relative to patients receiving no HF therapy.CONCLUSIONSA substantial portion of patients with HF may be receiving suboptimal pharmacotherapeutic care in real-world practice settings, potentially incurring large increases in hospitalizations and total costs. Quality improvement initiatives should seek to identify and manage those not being treated according to guideline recommendations.

Noninvasive stroke volume determination by Doppler echocardiography has traditionally required estimation both of mean flow rate during ejection by Doppler methods and of flow area by cross-sectional or M-mode echocardiography. 1 Spodick and Koito 2 recently reported a method for estimating stroke volume from Doppler echocardiographic tracings alone, which they term non-geometric because no area measurement is used. Instead, mean left ventricular ejection rate is estimated from mean Doppler velocity and is then multiplied by Doppler ejection time to yield stroke volume. We reasoned that if there is a physiologic relation between ejection rate and Doppler velocity, truly independent of aortic size, the nongeometric method should also accurately estimate stroke volume in infants and children, who have a wide range of aortic size.

Accurate assessment of pulmonary artery pressure and pulmonary vascular resistance are essential in children who may be candidates for Fontan's operation.1,2 In many such children, pulmonary blood flow is supplied primarily or entirely by systemic pulmonary arterial shunts. Because such shunts are frequently