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.

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).

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.

Diagnostic use of physicians' detection of urine fluorescence in a simulated ingestion of sodium fluorescein-containing antifreeze.

STUDY OBJECTIVE: We sought to assess physicians' ability to accurately determine the presence or absence of sodium fluorescein (SF) in urine at a concentration corresponding to that present after ingestion of a toxic amount of commercial automotive antifreeze. METHODS: We studied 2 different urine specimen evaluation formats--one presenting isolated specimens, and the other presenting specimens grouped for comparison--to determine whether the visual clues afforded by grouped comparison aided the accuracy of the evaluation. On each study day, 3 urine specimens (1 control specimen obtained before SF administration and 2 specimens obtained after SF administration) were obtained from each of 9 or 10 volunteers. Each of these 27 or 30 urine specimens were presented sequentially and in random order to 2 emergency physicians during separate evaluation time periods. Each physician was asked to classify each specimen as fluorescent or nonfluorescent (sequential format). After a rest period, each physician, again separately, was asked to look at the same 27 or 30 urine specimens, this time all together in a test tube rack so that grouped comparisons were possible. The physicians again classified each sample as either fluorescent or nonfluorescent (grouped format). We assessed sensitivity, specificity, and accuracy of the evaluation by each presentation format (sequential or grouped). RESULTS: Mean examiner sensitivity, specificity, and accuracy for detecting the presence of SF in urine using the sequential presentation format were 35%, 75%, and 48%, respectively, whereas the same test performance indices were 42%, 66%, and 50%, respectively, when the grouped format was used. CONCLUSION: Wood's lamp determination of urine fluorescence is of limited diagnostic utility in the detection of SF ingestion in an amount equivalent to toxic ingestion of some ethylene glycol--containing automotive antifreeze products.

Intravenous pyridoxine-induced metabolic acidosis.

STUDY OBJECTIVE: Pyridoxine hydrochloride, the antidote for isonicotinic acid hydrazide (INH)--induced seizures, is available in solution at a concentration of 100 mg/mL at a pH of less than 3. Pyridoxine is often infused rapidly in large doses for INH-induced seizures. Effects of pyridoxine infusion on base deficit in amounts given for INH poisoning have not been studied in human subjects. We hypothesized that this infusion would result in transient worsening of acidosis. METHODS: We conducted a randomized, controlled crossover trial in human volunteers. Five healthy volunteers (mean age, 35 years; range, 29 to 43 years) were randomized to receive intravenous placebo (50 mL of normal saline solution) or 5 g of pyridoxine (50 mL) over 5 minutes. A peripheral intravenous catheter was established in each arm, and a heparinized venous blood sample was obtained for base deficit at baseline and 3, 6, 10, 20, and 30 minutes after infusion. After at least a 1-week washout period, the volunteers were assigned to the alternate arms of the experiments, thus acting as their own control subjects. Data were analyzed by using the 2-tailed paired t test, controlling for multiple comparisons. RESULTS: No difference was noted between groups at baseline. A statistically significant increased base deficit was noted after the pyridoxine infusion versus control at 3 to 20 minutes but not at 30 minutes (P =.1). Maximal mean increase in base deficit (2.74 mEq/L) was noted at 3 minutes. CONCLUSION: A transient increase in base deficit occurs after the infusion of 5 g of pyridoxine in normal volunteers.

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.

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.

Hypertonic sodium bicarbonate is effective in the acute management of verapamil toxicity in a swine model.

STUDY OBJECTIVE: This study was conducted to determine whether hypertonic sodium bicarbonate would improve the hypotension associated with severe verapamil toxicity compared with volume expansion. METHODS: The study design used a nonblinded acute animal preparation. Twenty-four anesthetized and instrumented swine were poisoned with verapamil delivered at a rate of 1 mg/kg per hour for 10 minutes followed by incremental increases of 1 mg/kg per hour every 10 minutes until the endpoint of a mean arterial blood pressure of 45% of baseline was achieved. Animals alternately received either 4 mEq/kg of hypertonic sodium bicarbonate intravenously over 4 minutes or similar volumes of 0.6% sodium chloride in 10% mannitol (control). The main outcome parameter followed was mean arterial pressure. In addition, physiologic parameters including cardiac output, heart rate, pH, PCO (2), PO (2), plasma ionized calcium, sodium, and potassium were monitored. RESULTS: Verapamil toxicity, as defined by a mean arterial pressure of 45% of baseline, was produced in all animals following an average verapamil infusion dose of 0.6+/-0.12 mg/kg. This dose produced an average plasma verapamil concentration of 728.1+/-155.4 microgram/L, with no significant difference between groups. Swine treated with hypertonic sodium bicarbonate experienced a significant increase in mean arterial pressure (>50%) and cardiac output (>30%) over the first 20 minutes that slowly equilibrated with the control group over the remainder of the experiment. As expected, plasma sodium concentrations were elevated significantly in the sodium bicarbonate group while plasma potassium concentrations were decreased significantly. Finally, there was a significant decrease in plasma ionized calcium concentration in the sodium bicarbonate-treated group compared with controls. CONCLUSION: Hypertonic sodium bicarbonate reversed the hypotension and cardiac output depression of severe verapamil toxicity in a swine model.

Failure of intravenous N-acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial.

STUDY OBJECTIVE: To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in human volunteers. METHODS: We conducted a randomized, control crossover trial with each subject serving as his own control. Methemoglobinemia was induced with intravenous sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0. At time 30 minutes, subjects were randomly assigned to treatment with intravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg per hour for 40 minutes) or administration of an equal volume of 5% dextrose in water. Each subject received the alternative treatment after an interval of at least 1 week. Blood methemoglobin concentrations were measured by multiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minutes. Area under the methemoglobin concentration-time curve (AUC) between 30 and 130 minutes was compared between groups using a 2-tailed, paired t test. RESULTS: There were no statistically significant differences in the control and treatment groups with respect to baseline hemoglobin or methemoglobin concentrations, as well as nitrite-induced methemoglobin concentrations at the initiation of treatment (0.85+/-0.06 g/dL, 0.88+/-0.04 g/dL; mean+/-SEM; P =.31). Mean AUC for the control group (77.1+/-5.7 g x min/dL) was significantly lower than the mean AUC for the treatment group (84.5+/-4.7 g x min/dL); P =.01). CONCLUSION: Intravenous NAC failed to enhance methemoglobin reduction in this model.

Crack cocaine ingestion with prolonged toxicity requiring electrical pacing.

CASE REPORT: We report a 38-year-old man who experienced prolonged toxicity lasting over 16 hours from the time of ingestion of 1/4 ounce of crack cocaine. His illness included status epilepticus, wide and narrow complex bradyarrhythmias, ventricular arrhythmias, and delayed hyperthermia. His bradyarrhythmias were refractory to medicinal intervention and responsive to application of an external pacemaker. The patient recovered to his baseline state over the ensuing 48 hours.

The lack of transplacental movement of the cyanide antidote thiosulfate in gravid ewes.

UNLABELLED: A previous study reported that the co-infusion of IV sodium thiosulfate (STS) with sodium nitroprusside (SNP) to near-term gravid ewes prevented both maternal and fetal cyanide toxicity. We questioned whether maternally administered STS crossed the ovine placenta to enhance fetal transulfuration of cyanide, or whether the fetus was dependent on maternal detoxification of cyanide after diffusion of cyanide into the maternal circulation. Ten anesthetized, near-term gravid ewes underwent hysterotomies with delivery of fetal heads for venous catheterization. Five control ewes received IV isotonic sodium chloride solution, whereas five experimental ewes received IV STS (50 mg/kg over 15 min). Serial plasma thiosulfate concentrations in ewes and fetuses were measured over 135 min. Areas under the time-plasma thiosulfate concentration curves were calculated for experimental and control ewes at 2758+/-197 and 508+/-74 min x mg(-1) x L(-1), respectively (P < 0.008). Mean areas under the curve for experimental and control fetuses were 236+/-34 and 265+/-23 min x mg(-1) x L(-1), respectively (P > 0.5). Maternally administered STS may prevent fetal cyanide poisoning from SNP administration without relying on STS crossing the placenta into the fetal circulation. Fetal cyanide may cross down a concentration gradient from fetal to maternal circulation, to be transulfurated to thiocyanate in maternal tissues. IMPLICATIONS: We evaluated the mechanism of action of sodium thiosulfide (STS) in sodium nitroprusside-induced cyanide toxicity in the ewe. Fetal cyanide poisoning is alleviated by maternal administration of STS, although this cyanide antidote apparently does not cross the placenta.

Incidence of immediate and delayed hypersensitivity to Centruroides antivenom.

STUDY OBJECTIVE: To assess the incidence and course of immediate and delayed hypersensitivity to Centruroides antivenom. METHODS: We performed a 12-month prospective observation study, with telephone follow-up, evaluating the incidence of anaphylaxis or anaphylactoid reactions and serum sickness after Centruroides antivenom administration. The setting for the study was a poison control center and tertiary care toxicology treatment center. Participants included all patients who received Centruroides antivenom, and no interventions were performed. RESULTS: For immediate hypersensitivity reactions, 116 patients with grade III or IV envenomation received Centruroides antivenom; 77 of these patients were younger than 13 years. Three patients completed the infusion despite development of rash. A fourth patient with a history of atopy and asthma received epinephrine infusion and an inhaled beta-agonist for transient wheezing that quickly resolved; she was admitted for observation. Nine patients without hypersensitivity reactions were admitted for social reasons, for inappropriate sedation from drugs used before antivenom, or to rule out aspiration; all were discharged within 24 hours. The remaining 106 patients were discharged from the emergency department after resolution of symptoms. Thus 4 of 116 patients had immediate reactions. For patients with delayed reactions, 17 patients were lost to follow-up. Of 99 remaining patients, serum sickness developed in 61% (n=60), as defined by using liberal criteria. Serum sickness responded to oral steroids, antihistamines, or both; mean duration of symptoms with medication was 2.8 days. CONCLUSION: Anaphylactic reactions are uncommon after Centruroides antivenom infusion. Self-limited serum sickness that is easily controlled with corticosteroids and antihistamines commonly follows the use of Centruroides antivenom.

Renal failure and corrosive airway and gastrointestinal injury after ingestion of diluted diquat solution.

A 66-year-old man ingested 200 mL of Dexol Industries Weed and Grass Killer Concentrate (Torrance, CA), which contains 1.84% diquat dibromide, a herbicide structurally similar to paraquat. He remained asymptomatic for 8 hours, and then a sore throat and vomiting developed. Twenty hours after ingestion, esophagitis, mucositis, epiglottitis, and acute renal failure developed, from which he slowly recovered. This is the first report of systemic diquat toxicity from ingestion of a diluted diquat solution.

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.

Dexfenfluramine overdose.

Dexfenfluramine (Redux), the dextro-rotatory (+) steroisomer of fenfluramine, was previously approved for the treatment of weight control in the United States. We report a case of acute dexfenfluramine ingestion characterized by coma, clonus, and respiratory failure.