Medical Outcomes of Acute Aspirin Single Substance Poisoning in Pediatric Patients.

BACKGROUND: A consensus guideline on salicylate poisoning recommends referring patients to the emergency department if they ingested 150 mg/kg of aspirin. The dose of aspirin associated with severe poisoning in pediatric patients has not been investigated. OBJECTIVE: This study aims to associate medical outcomes with aspirin overdoses in patients 5 years old and younger. METHODS: A retrospective review of data on pediatric patients with single substance aspirin exposures reported from poison centers across the country was conducted. The primary endpoint was to associate aspirin doses with medical outcomes. Secondary endpoints included evaluation of the signs, symptoms, and treatments of ingestion and their association with medical outcomes. RESULTS: There were 26 488 included exposures with aspirin exposures resulting in no effect (92.5%), minor effect (6.0%), moderate effect (1.4%), major effect (0.2%), and death (0.02%). There were 8921 cases with available weight-based dosing information. Median doses associated with no effect, minor effects, moderate effects, major effects, and death ranged between 28.4 and 40.9 mg/kg, 52.5 and 82.3 mg/kg, 132.1 and 182.3 mg/kg, 132.3 and 172.8 mg/kg, and 142.2 and 284.4 mg/kg, respectively. Minor effect and moderate effect exposures were more likely to have alkalinization documented compared to no effect exposures (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.41-2.17; OR = 1.79, 95% CI = 1.12-2.86). There was no difference in rates of alkalinization between minor and moderate exposures (OR = 1.02, 95% CI: 0.61-1.7). CONCLUSIONS AND RELEVANCE: Reevaluation of the current recommendation of 150 mg/kg for referral to a healthcare facility is necessary for pediatric acute salicylate overdoses.

In vitro analysis of n-acetylcysteine (NAC) interference with the international normalized ratio (INR).

BACKGROUND: Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early publications focused on this interaction in the setting of an acetaminophen overdose and evaluated the INR of patients receiving intravenous NAC. However, there is limited literature describing the concentration-effect relationship of NAC to INR measurement in the absence of acetaminophen-induced hepatotoxicity at therapeutic NAC concentrations. The purpose of the study is to quantify the degree of interference of NAC on INR values at therapeutic concentrations correlating to each infusion of the regimen (ex. bag 1: 550 mcg/mL, bag 2: 200 mcg/mL, bag 3: 35 mcg/mL, double bag 3: 70 mcg/mL) and at supratherapeutic concentrations in vitro. METHODS: Blood samples were obtained from study volunteers. Each blood sample was transferred into vials containing 0.3 mL buffered sodium citrate 3.2% and spiked with various concentrations of NAC for final concentrations of 0, 35, 70, 200, 550, 1000, 2000, and 4000 mcg/mL. The samples were centrifuged and tested to determine PT and INR on two separate machines: Siemens CS-2500 and Stago SN1114559. We would require a sample size of 6 to achieve a power of 80% and a level of significance of 1.7% (two-sided). Differences between INRs at varying concentrations were determined by Friedman's test. For multiple comparisons, post hoc analysis was performed using Wilcoxon signed-rank test with Bonferroni adjustment. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Participants included 11 healthy subjects: 8 males, 3 females, median age 30 years (range 25 - 58). Median and interquartile ranges (IQR) INR for the baseline samples were 1.09 (IQR 1.05, 1.16) for Siemens and 1.03 (IQR 0.99, 1.11) for Stago analyzers. There was a significant difference in INR between the therapeutic concentrations (baseline, 35, 70,200, or 550 µg/mL) (Siemens p = .0008, Stago p < .0001). The 550 µg/mL concentration with the Siemens analyzer was the only one compared separately and found to be significantly greater than the baseline (1.07 vs 1.22, p = .02). For the Stago analyzer the 200 µg/mL and 500 µg/mL were compared and found to be significantly different from baseline (1.00 vs 1.07 and 1.19, adjusted p = .02 and p = .03, respectively). The largest INR increase seen was in one subject from a baseline of 1.07-1.32 with the 550 µg/mL concentration. Increases in concentrations to supratherapeutic levels resulted in a statistically significant non-linear increase in INR for all concentrations (Siemens p < .0001, Stago p < .0001). All of these concentrations were found to be significantly different from baseline (all adjusted p < .05). CONCLUSION: Although it was found that at therapeutic concentrations the in vitro presence of NAC affects INR measurements on two different machines, the change is of little clinical relevance. Supratherapeutic concentrations of NAC affect INR significantly, but the clinical utility of those results is limited by the rarity of those concentrations being measured.

Establishing Validity for a Vaginal Hysterectomy Simulation Model for Surgical Skills Assessment.

OBJECTIVE: To use the Messick validity framework for a simulation-based assessment of vaginal hysterectomy skills. METHODS: Video recordings of physicians at different levels of training and experience performing vaginal hysterectomy on a high-fidelity vaginal surgery model were objectively assessed using a modified 10-item Vaginal Surgical Skills Index, a one-item global scale of overall performance, and a pass-fail criterion. Participants included obstetrics and gynecology trainees and faculty from five institutions. Video recordings were independently assessed by expert surgeons blinded to the identities of the study participants. RESULTS: Fifty surgeons (11 faculty, 39 trainees) were assessed. Experience level correlated strongly with both the modified Vaginal Surgical Skills Index and global scale score, with more experienced participants receiving higher scores (Pearson r=0.81, P<.001; Pearson r=0.74, P<.001). Likewise, surgical experience was also moderately correlated with the modified Vaginal Surgical Skills Index and global scale score (Pearson r=0.55, P<.001; Pearson r=0.58, P<.001). The internal consistency of the modified Vaginal Surgical Skills Index was excellent (Cronbach's alpha=0.97). Interrater reliability of the modified Vaginal Surgical Skills Index and global scale score, as measured by the intraclass correlation coefficient, was moderate to good (0.49-0.95; 0.50-0.87). Using the receiver operating characteristic curve and the pass-fail criterion, a modified Vaginal Surgical Skills Index cutoff score of 27 was found to most accurately (area under the curve 0.951, 95% CI 0.917-0.983) differentiate competent from noncompetent surgeons. CONCLUSION: We demonstrated validity evidence for using a high-fidelity vaginal surgery model with the modified Vaginal Surgical Skills Index or global scale score to assess vaginal hysterectomy skills.

Outcomes of acute exploratory pediatric lithium ingestions.

Objectives: To date, very little literature describes the outcomes of acute unintentional ingestions of lithium in young children. This study aimed to describe the clinical effects and outcomes reported in these patients reported to the National Poison Data System (NPDS).Methods: This is a retrospective observational study of acute unintentional lithium ingestions in children <6 years of age. The primary intent of the study was to characterize acute unintentional exposures to lithium in children in this age group. As a secondary outcome, we sought to identify a weight-based threshold to empirically refer patients into a healthcare facility for symptoms consistent with moderate effect or worse. The American Association of Poison Control Centers' NPDS was queried for all acute ingestions of lithium salts in children <6 years of age from 2000 to 2018. Inclusion criteria were single substance ingestions, unintentional-general exposure (i.e., exploratory ingestion), and followed to a known outcome or coded as potentially toxic exposure unable to follow and the patient was experiencing symptoms.Results: A total of 3045 single-substance exploratory ingestions of lithium were reported to poison centers that showed a decrease over time, consistent with decreasing use of lithium and decreasing calls to poison centers. Of the 3045 cases, we excluded 1178 leaving 1863 cases for analysis. Median age was 2 years (IQR: 1.5, 2) with 51% male cases. Management site was primarily non-health care facility (n = 808; 43.4%) with 569 (30.5%) already in a healthcare facility (HCF) when the Poison Control Center (PCC) was called and 477 (25.6%) referred to a HCF. The route of exposure was most commonly ingestion (n = 1853; 99.5%) and site of exposure was primarily home (1743; 93.6%). Medical outcomes were predominantly no effect and minor effect. There were 262 related clinical effects were reported in 184 patients (10%). The most frequently reported were vomiting (n = 76), drowsiness/lethargy (n = 58), other (n = 22), and ataxia (n = 20). Clinical effects lasted ≤2 h for 65 (33%), 2-8 h for 57 (28.9%), 8-24 h for 51 (25.9%), 1-3 days for 11 (5.6%), and >3 days to ≤1 week for 1 (0.5%); no cases resulted in clinical effects thought to be permanent and no deaths were reported. There were 1173 treatments provided to 857 patients. The most common treatments were basic and are readily performed at home; dilution (n = 492) and food/snack (n = 180). A smaller subset of patients received care that could likely only be provided in a healthcare facility including IV fluids (n = 173), other (n = 120), whole bowel irrigation (n = 46), single dose activated charcoal (n = 41), syrup of ipecac (n = 34), and lavage (n = 31). No patients received hemodialysis. A total of 425 of the exposures were referred to a healthcare facility by the PCC which had a dose coded. There was no difference in dose that resulted to referral to a healthcare facility over time (p = 0.2747). Due to the small number of moderate/major effect cases with dose information, we were unable to identify a dose-based threshold for referral to HCF.Conclusions: Severe outcomes after unintentional ingestion of lithium in pediatric patients are rare. It is likely that most asymptomatic pediatric patients <6 years do not need to be referred to the hospital after ingestion of lithium.

Prime eligible poisons: identification of extremely hazardous substances available on Amazon.com®.

Background: Widespread use of the Internet has increased availability of numerous products. Multiple published cases highlight that toxic xenobiotics are available for purchase online. Most cases describe purchase from the deep web. We sought to identify extremely hazardous substances available from an online retailer.Methods: Over a 10-month period, the online retailer Amazon.com® was searched for each of the products listed by the Environmental Protection Agency's "List of Extremely Hazardous Substances." Product names, availability on Amazon Prime®, need for a business account, price, and quantity were collated.Results: We identified 79/340 (23.2%) of these substances were available on Amazon.com®. Almost one-third of the available substances were eligible for Amazon Prime®. Approximately one-third of the products were available in an amount that could be toxic by purchasing a single unit (31/79). Of these 31 products, only four required a business account, 18 were eligible for Amazon Prime®, and nine were neither eligible for Prime nor required a business account. Notable products include sodium azide, acrylamide, mercuric acetate, and hydrazine.Conclusions: The ease of purchase and ready availability of such highly toxic substances is concerning. Online retailers like Amazon.com® should consult with toxicologists or other qualified experts and governmental agencies to identify which products should be removed or restricted to business accounts.

Trends in types of calls managed by U.S. poison centers 2000-2015.

AIM: The number of cases reported to poison centers has decreased since 2008 but there is evidence that the complexity of calls is increasing. OBJECTIVES: The objectives are to evaluate national poison center data for trends in reason and how these changes effect management site, medical outcomes, and poison center workload. METHODS: Data regarding reason, age, management site, and medical outcome were extracted from annual reports of the National Poison Data System from 2000 to 2015. The proportion of cases by year were determined for unintentional and intentional exposures. Analysis of data from a single poison center from 2005 to 2015 compared the number of interactions between poison center staff and callers for unintentional versus intentional reasons. RESULTS: Trend analyses found that from 2000 to 2015 the percent of unintentional cases decreased (from 85.9 to 78.4%, p < .0001) and the percent of intentional cases increased (from 11.3 to 17.6%, p < .0001). Age distribution changed with a decrease in children <13 years of age and increase in adolescents and adults. In these latter two age groups, the proportion due to intentional exposure increased while unintentional declined. The distribution of management sites changed over the 16-year period, with a decrease in non-HCF cases and significant increase in percent of cases treated in a HCF. The frequencies of moderate effect, major effect, and death were significantly higher for intentional exposures than for unintentional exposures. Analysis of data entry notes from a single center showed that the mean number of notes per unintentional case (1.61 ± 0.08) was significantly different from the mean number of notes per intentional case (9.23 ± 0.68) (p < .0001). DISCUSSION: Poison centers are managing more intentional exposures and fewer unintentional exposures. Intentional exposures require more poison center staff expertise and time. CONCLUSION: Looking only at poison center total call volume may not be an adequate method to gauge productivity.

A Fluorescence Quenching Analysis of the Binding of Fluoroquinolones to Humic Acid.

Fluorescence quenching was used to investigate the interaction of six fluoroquinolones with humic acid. Static quenching was observed for the binding of ciprofloxacin, enoxacin, fleroxacin, levofloxacin, norfloxacin, and ofloxacin to humic acid. The equilibrium binding constants were found from Stern-Volmer plots of the data. The quenching experiments were repeated over a temperature range of 25-45 ℃ and van't Hoff plots were generated. From these linear plots, thermodynamic values were calculated for Δ H, Δ G, and Δ S for each of the fluoroquinolones. The equilibrium binding constants were found to be <1 for all the antibiotics studied. The calculated ΔH values were all negative and ranged from -9.5 to -27.6 kJ/mol. The high water solubility of the antibiotics and low ΔH of binding suggests that the antibiotics will be transported easily through the environment. Finally, whether the fluoroquinolones are in a protonated, deprotonated, or partially protonated state is found to correlate to the strength of binding to humic acid.

Toxalbumin exposures: 12 years' experience of U.S. poison centers.

BACKGROUND: Toxalbumins are natural plant toxins purported to be highly toxic. The purpose was to evaluate toxalbumin exposures reported to U.S. poison centers to determine plants involved and their toxicities. METHODS: A retrospective review of National Poison Data System data on acute toxalbumin exposures with known outcomes from 2000 through 2011 was performed. RESULTS: There were 1164 exposures. The majority involved one route (1135; 97.5%), mostly ingestions (904; 79.7%) or dermal (166; 14.3%). Most patients developed no effects (694; 59.6%) or minor effects (374; 32.1%). Moderate or major effects occurred in 8.3% with 66.6% ingestions and 23.9% dermal. There were no deaths. Exposures to the plants Ricinus communis and Robinia pseudoacacia were most common (33.8% and 32.9%, respectively), with gastrointestinal effects from R. communis (vomiting 19.6%, diarrhea 8.9%, nausea 7.9%) and dermal effects from R. pseudoacacia (puncture 28.7%, dermal irritation/pain 27.9%, and edema 13.3%). CONCLUSIONS: While toxalbumin plant exposures were generally well-tolerated, continued evaluation of risk is warranted since plants were primarily identified by the public. Major effects occurred in under 1% of cases overall, and not at all following unintentional ingestions. These findings should help allay concerns that unintentional ingestions of toxalbumin plants by young children will cause serious toxicity and possibly death.

Abuse and Intentional Misuse of Promethazine Reported to US Poison Centers: 2002 to 2012.

OBJECTIVE: Promethazine abuse has been reported. The objective was to investigate promethazine abuse/misuse in the United States. METHODS: An 11-year retrospective review was conducted of promethazine abuse and intentional misuse cases without co-ingestants in persons 10 years and older reported to the National Poison Data System. Data were stratified by product (promethazine-alone [PA] or co-formulation [PC]) and evaluated for demographics, toxicity, management sites, and outcomes. RESULTS: There were 354 single product abuse or misuse exposures-95 PA and 259 PC. Over the 11-year timeframe, the annual exposure rate per 100,000 population doubled. Exposures were most prevalent among 10 to 19 years old and young adults (20s), accounting for 69.5% of PA and 57.5% of PC cases. Clinical effects due to PA included drowsiness (43.2%), tachycardia (7.4%), agitation (13.7%), confusion (13.7%), slurred speech (12.6%), hallucinations (7.4%), dizziness (7.4%), and hypertension (5.3%). Drowsiness (53.4%) and tachycardia (20.8%) were more frequent with PC. There were significant differences between PA and PC in management site (P = 0.0078). Management sites for PA and PC, respectively, were emergency department (37.9%, 55.6%), non-health care facility (33.7%, 14.7%), critical care unit (8.4%, 11.2%), non-critical care unit (7.4%, 7.3%), psychiatry (2.1%, 4.2%), and other/unknown (10.5%, 7.0%). Outcomes for PA and PC, respectively, were no effect (21.0%, 12.4%), minor (58.9%, 53.7%), moderate (17.9%, 32.0%), and major effects (2.1%, 1.9%). CONCLUSIONS: Promethazine-alone abuse/misuse most frequently resulted in minor outcomes, and less than 20% required medical admission. Abuse/misuse of PC resulted in a higher frequency of health care facility treatment and a trend toward more moderate outcomes. These differences are most likely attributed to the co-formulate.

Evaluation of quetiapine abuse and misuse reported to poison centers.

OBJECTIVE: There are case reports of abuse of quetiapine, but no studies address quetiapine abuse or misuse. Most literature on the population that abuses quetiapine describes an older age group with previous substance abuse history, many of whom are in jail. The objective of this study was to evaluate national poison center data on misuse/abuse of quetiapine. METHODS: A retrospective study of American Association of Poison Control Centers National Poison Data System data from 2005 to 2011 on single substance quetiapine exposures coded as intentional misuse or abuse and followed to known outcome was performed. Data were evaluated for age, toxicity, management sites, treatments, and medical outcomes. RESULTS: There were 3116 cases meeting inclusion criteria; reason was misuse in 1948 cases and abuse in 1168 cases. The median age was 23 years. Misuse was reported most often in adults, whereas abuse occurred most frequently in adolescents. The male-to-female ratio was 1.7 for abuse and 1.0 for misuse. There were no deaths. Moderate or major toxicity occurred in 23.7% and 27.1% of misuse and abuse cases, respectively. Seventy-six percent were treated in the emergency department and/or received medical admission. CONCLUSIONS: Misuse was more common than abuse, except in adolescents for whom abuse was more frequent. Although outcomes were generally good, significant toxicity occurred in 25% of cases and more than 75% of the patients were treated in the emergency department and/or received medical admission. The consequences of nonmedical use of quetiapine are serious in some patients.

Investigating the binding of acridine, acridine orange, and acridine yellow G to humic acid through fluorescence quenching.

A fluorescence quenching method was used to determine the equilibrium binding constants for the association of acridine, acridine orange, and acridine yellow G to humic acid. The fluorescence of each polycyclic aromatic nitrogen heterocycle (PANH) was monitored as aliquots of humic acid were added, and a Stern-Volmer plot was produced in which the slope is the equilibrium constant of the binding reaction. The quenching experiments were performed at temperatures of 30, 35, 40, and 45 °C. A van't Hoff plot generated from the equilibrium binding constants as a function of temperature for a given PANH resulted in a linear plot. Calculation of the ΔHbinding, ΔGbinding, and ΔSbinding for each PANH leads to the conclusion that the equilibrium binding constant, and ΔGbinding, may be predictors of bioavailability. The other thermodynamic quantities, ΔHbinding and ΔSbinding, are helpful in understanding the relative binding of the compounds. For example, acridine yellow G appears to be the least bioavailable of the three PANHs studied because of its strong ΔHbinding = -29.8 kJ/mol, which leads to ΔGbinding = -0.71 kJ/mol. While acridine orange and acridine have similar ΔHbinding values, acridine orange is more likely to bind to humic acid because the ΔSbinding for the process is less negative. Thermodynamic values and equilibrium binding constants for all three compounds are reported.

Integrated lower extremity trauma simulator.

Severe limb trauma is prevalent in deployed U.S. Military forces since the advent of body armor. To improve outcomes, improved pre-deployment training is urgently needed. To meet this need, Simuluition Inc. and Melerit Medical AB are expanding the capabilities of the TraumaVision Simulator, originally designed for training surgeons in internal fixation procedures, to include training in battlefield relevant trauma care for fractured femurs and compartment syndrome. Simulations are being implemented for fractured femur reduction, external fixation, measuring intercompartment pressure (ICP), and performing fasciotomies. Preliminary validation work has begun to demonstrate content and construct validity of the TraumaVision simulator. Future work will include developing a SCORMs-compliant curriculum and completing the validation studies.

Acute, unintentional pediatric brodifacoum ingestions.

BACKGROUND: Brodifacoum is the major rodenticide used in the United States today. It is similar to warfarin but has more potent and prolonged effects. Large overdoses and chronic intoxication have been associated with significant coagulopathies and death. Currently, the management of acute unintentional ingestions by young children is controversial. METHODS: American Association of Poison Control Centers (AAPCC) data from 1993 to 1996 were retrospectively searched for acute, unintentional brodifacoum exposures without coingestions followed-up to a known outcome in children aged 6 years and younger. The cases were analyzed by management site, symptoms, therapy, and outcome. Cases coded as having clinical or laboratory evidence of coagulopathy were further evaluated for severity. RESULTS: Our study reviewed 10,762 cases that involved single, acute, unintentional ingestions of brodifacoum. All of the patients were followed-up to a known outcome as defined by AAPCC data collection standards. In this cohort, there were no deaths or major effects reported. Although 67 patients reported evidence of coagulopathy, no major effects or deaths were reported. Minor and moderate effects were reported in 38 and 54 children, respectively. Management occurred outside of a healthcare facility in 5404 (50.2 %) cases. Approximately half of all the children received some form of gastrointestinal decontamination. Decontamination had no effect on the distribution of outcomes. Adverse effects from decontamination therapy were reported in 42 patients. CONCLUSION: Acute pediatric ingestions of brodifacoum rarely caused clinical effects and were not associated with life-threatening symptoms or death in young children. It seems reasonable that acute unintentional ingestions of small quantities of brodifacoum by young children can be adequately managed with home observation and parent education.

Accidental injection of epinephrine from an autoinjector: invasive treatment not always required.

BACKGROUND: Individual case reports of accidental injection with epinephrine appear in the literature and seem to represent the worst case scenarios. We present a case series of 28 exposures to epinephrine via autoinjector. METHOD: All accidental parenteral injections of epinephrine by autoinjector reported to two regional poison information centers over a 2-year period were included. RESULTS: Injection sites included digits (23 cases), palm (4 cases), and thigh (1 case). Symptoms included swelling, pallor, pain, and erythema. Four patients reported no effect, and 9 required no treatment. Ten patients obtained relief with warm soaks, 1 patient had massage only, and 2 patients were lost to follow-up. Fourteen were examined in the emergency department, and 14 were treated at home. CONCLUSION: Although some injection injuries must be treated in an emergency facility, many can be treated at home. Immediate referral to a health care facility is not needed in all cases and at times is unwarranted.