A computerized scoring system to improve assessment of heparin-induced thrombocytopenia risk.

Essentials Current risk scores for heparin-induced thrombocytopenia (HIT) are not computer-friendly. We compared a new computerized risk score with the 4Ts score in a large healthcare system. The computerized risk score agrees with the 4Ts score 85% of the time. The new score could potentially improve HIT diagnosis via incorporation into decision support. SUMMARY: Background (HIT) is an immune-mediated adverse drug event associated with life-threatening thrombotic complications. The 4Ts score is widely used to estimate the risk for HIT and guide diagnostic testing, but it is not easily amenable to computerized clinical decision support (CDS) implementation. Objectives Our main objective was to develop an HIT computerized risk (HIT-CR) scoring system that provides platelet count surveillance for timing and degree of thrombocytopenia to identify those for whom diagnostic testing should be considered. Our secondary objective was to evaluate clinical management and subsequent outcomes in those identified as being at risk for HIT. Methods We retrospectively analyzed data from a stratified sample of 150 inpatients treated with heparin to compare the performance of the HIT-CR scoring system with that of a clinically calculated 4Ts score. We took a 4Ts score of ≥ 4 as the gold standard to determine whether HIT diagnostic testing should be performed. Results The best cutoff point of the HIT-CR score was a score of 3, which yielded 85% raw agreement with the 4Ts score and a kappa of 0.69 (95% confidence interval 0.57-0.81). Ninety per cent of patients with 4Ts score of ≥ 4 failed to undergo conventionally recommended diagnostic testing; 38% of these experienced persistent, unexplained thrombocytopenia, and 4% suffered life-threatening thrombotic complications suggestive of undiagnosed HIT. Conclusion The HIT-CR scoring system is practical for computerized CDS, agrees well with the 4Ts score, and should be prospectively evaluated for its ability to identify patients who should be tested for HIT.

Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia.

Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated 'four Ts' (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93-1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95-99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48-0.98), specificity 0.99 (95% CI, 0.97-1.00), PPV 0.90 (95% CI, 0.56-0.99) and NPV 0.99 (95% CI, 0.96-1.00). Conclusions An algorithm incorporating 4Ts scoring and a stratified interpretation of the anti-PF4/H ELISA has good operating characteristics and the potential to improve management of suspected HIT patients.

Refractory hypoglycemia secondary to topical salicylate intoxication.

We describe a case of severe refractory hypoglycemia secondary to topical salicylate intoxication. A 72-year-old man with psoriasis and end-stage renal disease was treated with a topical cream containing 10% salicylic acid. The patient presented with encephalopathy and subsequently developed hypoglycemia refractory to infusions of large amounts of glucose. A serum salicylate concentration was elevated at 3.2 mmol/L. Emergent hemodialysis was accompanied by rapid lowering of serum salicylate concentration and resolution of refractory hypoglycemia. Salicylate is well absorbed across normal and diseased skin. Salicylate markedly impairs gluconeogenesis and increases glucose utilization, resulting in hypoglycemia. To our knowledge, this is the first article on hypoglycemia due to the application of topical salicylate.

Rattlesnake envenomations: unusual case presentations.

Rattlesnake envenomations are common in some areas of the United States. Although fatal rattlesnake envenomations are rare and usually preventable, morbidity may be significant. Patients may present with localized edema, hypotension, coagulopathy, or thrombocytopenia. Patients with progressive swelling or severe coagulopathy are typically treated with Crotalidae polyvalent antivenin. We present a series of 4 patients with unusual complications of rattlesnake envenomation to illustrate the wide spectrum of disease that may be encountered. These case presentations include anaphylaxis to rattlesnake venom, an acute airway emergency, progressive and marked edema with a large pleural fluid collection, and death.

Acute lead poisoning in nursing home and psychiatric patients from the ingestion of lead-based ceramic glazes.

To our knowledge, acute inorganic lead poisoning from single ingestions of lead compounds has been only rarely reported. During a 14-month period, we were contacted regarding eight instances of acute ingestions of liquid lead-based ceramic glazes by mentally impaired residents of nursing homes or psychiatric facilities participating in ceramic arts programs. While some ingestions did not cause toxic effects, some patients developed acute lead poisoning characterized by abdominal pain, anemia, and basophilic stippling of red blood cells. In the blood of several patients, lead concentrations were far above normal (4 to 9.5 mumol/L). Urinary lead excretions were tremendously elevated during chelation therapy, with one patient excreting 535.9 mumol/L of lead during a 6-day period, the largest lead excretion ever reported in a patient suffering from acute lead poisoning, to our knowledge. All patients recovered following supportive care and appropriate use of chelating agents. Lead-based glazes are commonly found in nursing homes and psychiatric facilities. We suspect that acute or chronic lead poisoning from the ingestion(s) of lead-based ceramic glazes may be an unrecognized but not uncommon problem among such residents. We urge physicians to take ingestions of lead-based glazes seriously and to consider the diagnosis of lead poisoning in nursing home and psychiatric patients who have participated in ceramic crafts programs.

A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States.

BACKGROUND: Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). METHODS: A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. RESULTS: The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P<.001); there was no difference between scheduled and PRN groups. No patient in the scheduled group received unplanned Fab AV doses, but 8 of 16 patients in the PRN group received unplanned doses (P =.002). Acute reactions occurred in 6 patients (19%), and serum sickness occurred in 6 (23%) of 26 patients who returned for follow-up. CONCLUSIONS: In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

Pool cue chalk: a source of environmental lead.

Lead compounds are used as coloring agents for numerous products. Two cases of children with elevated blood lead concentrations encountered by the authors suggested that pool cue chalk may serve as a source of environmental lead. The objective of this study was to determine lead content of various brands and colors of pool cue chalk. Atomic absorption analyses were conducted of 23 different types of pool cue chalk for lead content. Three of 23 types of pool cue chalk contained more than 7000 ppm (mg/kg) lead: one manufacturer's green and tangerine chalk and another manufacturer's green chalk. It was concluded that some brands of pool cue chalk contain relatively large amounts of lead and could contribute to childhood lead poisoning.

Effect of magnesium hydroxide on iron absorption following simulated mild iron overdose in human subjects.

OBJECTIVE: To determine the effect of oral magnesium hydroxide [Mg(OH)2] on iron absorption after simulated iron overdose in human subjects. METHODS: A randomized, controlled crossover study was conducted in healthy adult male human volunteers taking no medications. Subjects received an average of 5.0 mg/kg elemental iron orally followed 1 hour later by either oral administration of 4.5 g of Mg(OH)2 per g ingested elemental iron or no treatment. Serial serum specimens were obtained over the 12 hours following iron ingestion and stored at -60 degrees C until standard serum iron assay was performed. After a 2-week washout period, the subjects were enrolled in the alternative trial arm. Individual baseline diurnal variation in serum iron levels was determined over a 12-hour period on the day prior to each trial. Area under time-concentration curves (AUCs) were calculated, and the AUC due to experimental iron ingestion (deltaAUC) was determined by subtracting the baseline diurnal AUC from the experimental AUC for each subject. RESULTS: Thirteen healthy adult male subjects were enrolled. Mean +/- SEM for deltaAUC due to experimental iron ingestion followed by treatment with Mg(OH)2, 78 +/- 23 micromol(hr)/L, was significantly less than that followed by no treatment, 144 +/- 33 micromol(hr)/L (p = 0.03 by signed rank test). CONCLUSIONS: Magnesium hydroxide, administered 1 hour post-iron ingestion at an oral dose of 4.5 g per g elemental iron ingested, significantly reduced iron absorption during a 12-hour period following simulated mild iron overdose in healthy adult human volunteers.

Toxic effects of drugs used in the ICU. Nitroprusside, nitroglycerin, and angiotensin-converting enzyme inhibitors.

Sodium nitroprusside causes cyanide poisoning at currently recommended infusion rates. Serum thiocyanate concentrations are of no value in detecting cyanide poisoning caused by nitroprusside. Methemoglobinemia in those patients receiving intravenous nitroglycerin may seriously impair oxygen delivery and is not always accompanied by cyanosis in anemic patients. Angiotensin-converting enzyme inhibitors are responsible for a plethora of adverse effects, including renal insufficiency, hypotension, angioedema, cough, and increased insulin sensitivity.

Poisoning by sodium channel blocking agents.

Poisoning by drugs that block voltage-gated sodium channels produces intraventricular conduction defects, myocardial depression, bradycardia, and ventricular arrhythmias. Human and animal reports suggest that hypertonic sodium bicarbonate may be effective therapy for numerous agents possessing sodium channel blocking properties, including cocaine, quinidine, procainamide, flecainide, mexiletine, bupivacaine, and others.

Crotalid snake envenomation.

Over 5000 Americans suffer from snake bites annually, and of these, nearly one quarter are from poisonous species. Although these cases are undeniably reported, death appears to occur in only a few cases each year, and often reflects delay in obtaining medical care. Two families of venomous snake indigenous to the United States account for most envenomations: Crotalidae (pit vipers or new world vipers) and Elapidae. This article focuses on the snakes of the Crotalidae family.

Acute iron poisoning.

Acute iron poisoning continues to be one of the most common and deadly poisonings seen by emergency physicians. There are many potential pitfalls in the assessment, diagnosis, and treatment of iron-poisoned patients. This article reviews the pathophysiology of acute iron poisoning and describes a comprehensive management plan that will enable emergency physicians to provide appropriate emergency care to patients ingesting iron preparations. This article also addresses the common problems encountered by clinicians who care for iron-poisoned patients once they are admitted to the hospital.

Marijuana.

Marijuana remains a complex, poorly understood drug with many effects. Although its acute psychological effects are well described, data linking cannabis use to chronic psychiatric or social problems and decreased driving or workplace safety are much less clear. Current laboratory procedures have not yet been shown useful to demonstrate acute intoxication, so they remain screening instruments for those interested in detecting cannabis use for other reasons. Although both acute and chronic effects of marijuana use have been described, they appear to be less than other commonly abused substances, including tobacco and alcohol. The rare acute complications that present to the Emergency Department can be managed with conservative measures.

Clinical toxicology of ethylene glycol monoalkyl ethers.

The glycol ethers constitute a family of organic solvents commonly found in industrial and household products. Because of their widespread availability and potential for serious toxicity, physicians should be aware of the clinical toxicology of these compounds. Until recently, knowledge of the toxic effects of glycol ethers has been derived from animal studies and a limited number of case reports and small case series. A growing body of data from epidemiological studies, controlled human studies, and studies using human tissue now allows for advancement in the understanding of the acute and chronic toxicity of these compounds. This review summarizes and evaluates human and pertinent animal literature on the clinical toxicology of glycol ethers, with a focus on the commonly encountered monoalkyl ethers of ethylene glycol. Management options for acute poisoning, as well as measures for the control of workplace exposures, are discussed.

Effect of glycol ethers on plasma osmolality.

1. Glycol ethers and their alkoxyacetic acid metabolites produce a linear increase in plasma osmolality with increasing plasma concentration. 2. This change in osmolality may be too small to be clinically useful at concentrations expected in cases of acute human glycol ether poisoning.

Outcomes following abuse of methanol-containing carburetor cleaners.

INTRODUCTION: Carbureter cleaners may contain methanol and are abused via inhalation. Toxicity resulting from the methanol component of these products is poorly described. METHODS: We conducted a retrospective poison center chart review over a four-year period (3/98-3/02) of outcomes following methanol-containing carbureter cleaners (MCC) exposure. Inclusion criteria were: (1) use of MCC, (2) evaluation in health care facility (HCF), (3) no known co-ingestion exposure and (4) at least 12 hour follow-up. RESULTS: 33 cases were reviewed with 11 cases excluded because of significant co-ingestions. Of the remaining 22 cases the mean age was 17 [range: 14-41] years old with 90% of cases between 14 and 17 years old. Six women and 16 men were in the study. Six of 22 cases had acidosis (serum bicarbonate < or =22 mmol/L or pH < or =7.35), 100% of patients had neurological symptoms (ataxia, etc.) and 14/22 had vomiting on presentation. Three patients received treatment with ethanol (1) and fomepizole (2). All others received intravenous fluids (15) or no treatment (4). Mean serum methanol concentration was 28mg/dl [range: 0-341 with 17/22 developing acidosis. Serum methanol was obtained at a mean of 3.5 hours [range 1-7 hours] post use. All metabolic disturbances resolved within 24 hours except in one patient (41 years old) in which her disturbances resolved within 72 hours. No patient developed visual disturbances or neurological sequealae. CONCLUSIONS: Significant toxicity following inhalation of MCC was rare with symptoms improving without aggressive care (dialysis, alcohol dehydrogenase blockade).

Combined ingestion and subcutaneous injection of elemental mercury.

A 40-year-old man with a history of schizophrenia and inflammatory soft tissue lesions after self-injection of elemental mercury presented to the Emergency Department. Multiple skin abscesses associated with fever required operative debridement. An incidental finding of oral mercury ingestion was followed clinically and did not result in complications. Exposure to elemental mercury through injection or ingestion is an uncommon event, but one the Emergency Physician may encounter. Subcutaneous mercury injection should be managed with local wound debridement, whereas ingestions are rarely of clinical significance.

Lack of evidence for a percent saturation gap in cyanide poisoning.

STUDY OBJECTIVES: To determine if toxic concentrations of cyanide in blood result in a difference between calculated and measured percent hemoglobin oxygen saturation (percent saturation gap). DESIGN: An in vitro laboratory study. SETTING: Hospital laboratory. TYPE OF PARTICIPANTS: Arterial blood from five stable patients residing in a tertiary hospital ICU. Venous blood samples obtained from five healthy volunteers. INTERVENTIONS: Two-mL aliquots from each blood sample were placed into four test tubes and mixed with phosphate buffer. Cyanide was added to three of the tubes so that the four tubes contained 0, 6, 12, and 25 mg/L cyanide. MEASUREMENTS AND MAIN RESULTS: The percent saturation gap was calculated by subtracting the percent oxyhemoglobin measured on an oximeter from the percent saturation calculated by a blood gas analyzer. Using two-tailed, paired t tests, we could not demonstrate a difference in mean percent saturation gaps between arterial samples or venous samples with and without cyanide. All blood samples had a normal percent saturation gap (P greater than .99 by Fisher's exact test). We had greater than a 95% chance of demonstrating a difference in mean percent saturation gaps of only 0.46% in arterial blood and of 3.3% in venous blood if such a difference existed. CONCLUSIONS: Our results, as well as a review of the literature, indicate that there are no data supporting the suggestion that a percent saturation gap should imply the diagnosis of poisoning by inorganic cyanide.

Seizure after isolated fluoxetine overdose.

Previous case reports of seizures following fluoxetine overdose have not adequately ruled out ingestion of other substances and have lacked documentation of increased serum drug levels. We present a case of seizure following fluoxetine overdose in a previously well patient with a clear history of sole ingestion. We ruled out the presence of other substances with comprehensive drug screening and documented increased serum levels of fluoxetine and its active metabolite.