Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series.

INTRODUCTION: Acetaminophen (N-acetyl-para-aminophenol or APAP) is the leading cause of acute liver failure worldwide. Standard therapy for APAP overdose is with IV N-acetylcysteine (NAC). However, overdose patients treated with NAC can still incur hepatotoxicity in some circumstances. Fomepizole has proven safety in methanol and ethylene glycol poisoning and is a potent CYP2E1 and c-Jun-N-terminal Kinase (JNK) inhibitor that is effective even in the metabolic phase. METHODS: We present a prospective case series of 14 consecutive, high-risk patients who had elevated APAP levels after overdose who were treated with fomepizole as an adjunct to standard IV-NAC. The attending toxicologist utilized clinical judgement to determine the use of fomepizole, especially if APAP levels persisted due to altered half-life or risk factors for toxicity. RESULTS: There were no unfavorable outcomes in any patient, which were better than expected. CONCLUSIONS: This case series has demonstrated the safety of fomepizole in high-risk APAP overdose. The efficacy of fomepizole needs to be further elucidated through controlled clinical trials on a larger scale. In massive APAP overdoses, fomepizole should be considered as an adjunct due to the known failure rate of NAC and the safety profile of fomepizole.

Gabapentin prevalence: clinical and forensic experience in St. Louis, Missouri, USA.

Gabapentin (Neurontin) is an anti-epileptic drug that has had wide off-label prescription use since market release due to presumed negligible abuse potential. However, trends in drug misuse have demonstrated that gabapentin misuse is occurring, particularly in those with a history of opioid misuse. This is concerning, because although gabapentin has no direct ligand activity at opioid receptors, it does potentiate the analgesic effect of opioids, and concurrent use of gabapentin and opioids may increase the risk of respiratory depressive effects of opioids. This study investigates the incidence of gabapentin detected in urine samples collected for clinical drug screening purposes in a local hospital emergency department and in postmortem samples submitted by medical examiners in the St. Louis metropolitan area. The prevalence of gabapentin and co-detected drugs in both populations is contrasted, compared, and discussed. This study found that 30% of urine samples collected from patients with suspected drug intoxication presenting to SSM Health Saint Louis University Hospital, a quaternary care medical center, were positive for gabapentin, and nearly two thirds of those were also positive for oxycodone. Over a 6-month period, the incidence of gabapentin positive postmortem cases increased from 18% to 20%. Nearly all gabapentin positive postmortem cases were also positive for an opioid, the most significant being fentanyl, suggesting that gabapentin misuse may be due to its potentiating effect of opioid drug action. This study also highlights the limited utility of immunoassay-based urine drug screens.

Heightened Immune Response to Presumed Loxosceles reclusa Envenomation.

Loxoscelism is a systemic inflammatory reaction in response to a brown recluse spider bite (BRSB). In this case we describe a patient with a heightened inflammatory response to a presumed BRSB, with Coomb's positive hemolysis, cytoplasmic antineutrophil cytoplasmic antibody (cANCA) vasculitis, and features of hemophagocytic lymphohistiocytosis (HLH). A 24-y-old female presented with sudden pain and swelling to her lower back, nausea, fever, and tachycardia after a presumed BRSB. Hemolysis began on hospital day 3 (15.9 g·dL-1) with a nadir on hospital day 5 (6.3 g·dL-1). She had an lactate dehydrogenase of 1415 U·L-1, ferritin of 15534 ng·mL-1, persistent fever, and signs of bone marrow suppression despite hemolysis, with thrombocytopenia (100,000 µL-1) and an inadequate reticulocyte response (1.7%) suggestive of HLH. The patient's blood was Coomb's and cANCA/antiproteinase 3 positive. She had signs of toxin-induced vasculitis, with respiratory failure requiring bilevel positive airway pressure, radiographs with bilateral pulmonary infiltrates, and a desquamating rash. She received 6 U of packed red blood cells, furosemide for pleural and pericardial effusions, antibiotics, and symptomatic treatment during the acute phase of her illness. Hemolysis improved without glucocorticoids by hospital day 6. The patient demonstrated a dysregulated immunologic and complement-mediated response to the presumed BRSB. The triad of Coomb's positive hemolysis, cANCA vasculitis, and HLH-like reaction associated with a presumed BRSB is described for the first time in the literature and brings up questions for future research regarding the role of immune modulators and complement inhibitors in the treatment of severe loxoscelism as well as the genetic factors that predispose certain individuals to such reactions.

Poisoning, Overdoses, Toxic Exposures.

The national poison center movement originated in the Midwest with actions of the American Academy of Pediatrics in Chicago, Illinois, in 1972. The Missouri Poison Center (MPC) was established in 1974. The MPC and other regional poison centers are essential to the public health locally and nationally. Trends in serious poisoning outbreaks such as the release of synthetic cannabinoids have been detected by real-time electronic surveillance by specialists in poison information and medical toxicologists.

Validity Evidence for a Serious Game to Assess Performance on Critical Pediatric Emergency Medicine Scenarios.

INTRODUCTION: We developed a first-person serious game, PediatricSim, to teach and assess performances on seven critical pediatric scenarios (anaphylaxis, bronchiolitis, diabetic ketoacidosis, respiratory failure, seizure, septic shock, and supraventricular tachycardia). In the game, players are placed in the role of a code leader and direct patient management by selecting from various assessment and treatment options. The objective of this study was to obtain supportive validity evidence for the PediatricSim game scores. METHODS: Game content was developed by 11 subject matter experts and followed the American Heart Association's 2011 Pediatric Advanced Life Support Provider Manual and other authoritative references. Sixty subjects with three different levels of experience were enrolled to play the game. Before game play, subjects completed a 40-item written pretest of knowledge. Game scores were compared between subject groups using scoring rubrics developed for the scenarios. Validity evidence was established and interpreted according to Messick's framework. RESULTS: Content validity was supported by a game development process that involved expert experience, focused literature review, and pilot testing. Subjects rated the game favorably for engagement, realism, and educational value. Interrater agreement on game scoring was excellent (intraclass correlation coefficient = 0.91, 95% confidence interval = 0.89-0.9). Game scores were higher for attendings followed by residents then medical students (Pc < 0.01) with large effect sizes (1.6-4.4) for each comparison. There was a very strong, positive correlation between game and written test scores (r = 0.84, P < 0.01). CONCLUSIONS: These findings contribute validity evidence for PediatricSim game scores to assess knowledge of pediatric emergency medicine resuscitation.

Can Residents Assess Other Providers' Infant Lumbar Puncture Skills?: Validity Evidence for a Global Rating Scale and Subcomponent Skills Checklist.

OBJECTIVES: The aims of this study were to provide validity evidence for infant lumbar puncture (ILP) checklist and global rating scale (GRS) instruments when used by residents to assess simulated ILP performances and to compare these metrics to previously obtained attending rater data. METHODS: In 2009, the International Network for Simulation-based Pediatric Innovation, Research, and Education (INSPIRE) developed checklist and GRS scoring instruments, which were previously validated among attending raters when used to assess simulated ILP performances. Video recordings of 60 subjects performing an LP on an infant simulator were collected; 20 performed by subjects in 3 categories (beginner, intermediate, and expert). Six blinded pediatric residents independently scored each performance (3 via the GRS, 3 via the checklist). Four of the 5 domains of validity evidence were collected: content, response process, internal structure (reliability and discriminant validity), and relations to other variables. RESULTS: Evidence for content and response process validity is presented. When used by residents, the checklist performed similarly to what was found for attending raters demonstrating good internal consistency (Cronbach α = 0.77) and moderate interrater agreement (intraclass correlation coefficient = 0.47). Residents successfully discerned beginners (P < 0.01, effect size = 2.1) but failed to discriminate between expert and intermediate subjects (P = 0.68, effect size = 0.34). Residents, however, gave significantly higher GRS scores than attending raters across all subject groups (P < 0.001). Moderate correlation was found between GRS and total checklist scores (P = 0.49, P < 0.01). CONCLUSIONS: This study provides validity evidence for the checklist instrument when used by pediatric residents to assess ILP performances. Compared with attending raters, residents appeared to over-score subjects on the GRS instrument.

Modafinil Moderates the Relationship Between Cancer-Related Fatigue and Depression in 541 Patients Receiving Chemotherapy.

OBJECTIVE: The aim of this study was to examine the effect of modafinil on depression via a secondary data analysis of a randomized clinical trial of modafinil for fatigue in cancer patients. The primary aim is to elucidate factors that contributed to the effectiveness of modafinil in the parent trial. METHODS: Five hundred forty-one cancer patients receiving chemotherapy and experiencing fatigue (Brief Fatigue Inventory [BFI] item 3 of ≥3) were randomized to receive 200 mg modafinil (n = 260) or placebo (n = 281) daily from baseline (cycle 2) to posttest (cycle 4). Patients completed the Center for Epidemiological Studies-Depression Scale (CES-D) and Profile of Mood States depression-dejection subscale at baseline and posttest. We used linear regression to address the hypothesis that modafinil would be associated with reduced depression, particularly in those experiencing severe fatigue (BFI ≥7). RESULTS: Modafinil did not have a significant effect on depression, even for those patients with severe fatigue. However, for subjects with severe fatigue (BFI ≥7), those receiving modafinil had lower depression scores than did control subjects. Modafinil significantly moderated the relationship between baseline fatigue and CES-D total scores (P = 0.04) and was marginally significant as a moderator for the relationship between baseline fatigue and Profile of Mood States depression-dejection subscale scores (P = 0.07). Modafinil also significantly moderated the relationship between baseline fatigue and CES-D positive affect subscale scores (P = 0.003), but not CES-D somatic, negative affect, or interpersonal subscale scores. CONCLUSIONS: Modafinil differentially impacts depression based on a patient's level of fatigue and reduced depressive symptoms only in those with extreme fatigue. This effect may be driven by increases in positive affective symptoms. These results have significant implications for intervention; in patients with high levels of fatigue, modafinil might also reduce depression. Future randomized clinical trials are needed to confirm these results.

Simulation training for pediatric residents on central venous catheter placement: a pilot study.

OBJECTIVE: To assess the effect of simulation training on pediatric residents' acquisition and retention of central venous catheter insertion skills. A secondary objective was to assess the effect of simulation training on self-confidence to perform the procedure. DESIGN: Prospective observational pilot study. SETTING: Single university clinical simulation center. SUBJECTS: Pediatric residents, postgraduate years 1-3. INTERVENTIONS: Residents participated in a 60- to 90-minute ultrasound-guided central venous catheter simulation training session. Video recordings of residents performing simulated femoral central venous catheter insertions were made before (baseline), after, and at 3-month following training. Three blinded expert raters independently scored the performances using a 24-item checklist and 100-mm global rating scale. At each time point, residents rated their confidence to perform the procedure on a 100-mm scale. MEASUREMENTS AND MAIN RESULTS: Twenty-six residents completed the study. Compared with baseline, immediately following training, median checklist score (54.2% [interquartile range, 40.8-68.8%] vs 83.3% [interquartile range, 70.0-91.7%]), global rating score (8.0 mm [interquartile range, 0.0-64.3 mm] vs 79.5 mm [interquartile range, 16.3-91.7 mm]), success rate (38.5% vs 80.8%), and self-confidence (8.0 mm [interquartile range, 3.8-19.0 mm] vs 52.0 mm [interquartile range, 43.5-66.5 mm]) all improved (p < 0.05 for all variables). Compared with baseline, median checklist score (54.2% [interquartile range, 40.8-68.8%] vs 54.2% [interquartile range, 45.8-80.4%], p = 0.47), global rating score (8.0 mm [interquartile range, 0.0-64.3 mm] vs 35.5 mm [interquartile range, 5.3-77.0], p = 0.62), and success rate (38.5% vs 65.4%, p = 0.35) were similar at 3-month follow-up. Self-confidence, however, remained above baseline at 3-month follow-up (8.0 mm [interquartile range, 3.8-19.0 mm] vs 61.0 mm [interquartile range, 31.5-71.8 mm], p < 0.01). CONCLUSIONS: Simulation training improved pediatric residents' central venous catheter insertion procedural skills. Decay in skills was found at 3-month follow-up. This suggests that simulation training for this procedure should occur in close temporal proximity to times when these skills would most likely be used clinically and that frequent refresher training might be beneficial to prevent skills decay.

Validation of global rating scale and checklist instruments for the infant lumbar puncture procedure.

INTRODUCTION: The Patient Outcomes in Simulation Education network has developed tools for the assessment of competency to perform the infant lumbar puncture (ILP) procedure. The objective of this study was to evaluate the validity and reliability of these tools in a simulated setting. METHODS: We developed a 4-point anchored global rating scale (GRS) and 15-item dichotomous checklist instrument to assess ILP performance in a simulated environment. Video recordings of 60 subjects performing an unsupervised lumbar puncture on an infant bench top simulator were collected prospectively; 20 performed by subjects in each of 3 categories (beginner, intermediate experienced, or expert). Three blinded, expert raters independently scored each subject's video recording using the GRS and checklist instruments. RESULTS: The final version of the scoring instruments is presented. Across all subject groups, higher GRS scores were found with advancing level of experience (P < 0.01). Total checklist scores were similar between the expert and intermediate experienced groups (P = 0.54). Both groups scored higher than the beginner group on the checklist instrument (P < 0.01). For each rater, a significant positive correlation was found between GRS scores and total checklist scores (median ρ = 0.75, P < 0.01). Cronbach α coefficient for the checklist was 0.77. The intraclass correlation coefficients between raters for the GRS and total checklist scores were 0.71 and 0.52, respectively. CONCLUSIONS: This study provides some initial evidence to support the validity and reliability of the ILP-anchored GRS. Acceptable internal consistency was found for the checklist instrument. The GRS instrument outperformed the checklist in its discriminant ability and interrater agreement.

The effect of simulation training on PALS skills among family medicine residents.

BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education requires that family medicine residents receive structured skills training on pediatric advanced life support (PALS) and should learn procedures for medical emergencies in patients of all ages. Traditional methods of training family medicine residents in PALS is challenging given their limited clinical exposure to critically ill patients. The primary objective of this study was to assess the effect of a 2-hour PALS training session utilizing high-fidelity mannequins on residents' psychomotor skills performances. METHODS: Between February and June 2009, residents from two urban family medicine residency programs received training on four PALS procedures (bag-mask ventilation, tracheal intubation, intraosseous line placement, and cardiac rhythm assessment/defibrillation) at a university simulation center. Residents completed questionnaires to provide data on previous resuscitation training and experience. We collected self-confidence data and video recordings of residents performing the procedures before and after training. To assess retention at 6 months, we collected self-confidence data and video recordings of PGY-1 and PGY-2 residents performing the procedures. A blinded reviewer scored the video recordings. RESULTS: Forty-seven residents completed the study. The majority of residents (53.2%) had never performed any of the procedures on a real patient. Immediately following skills training, mean overall performance improved from 39.5% (± 11.5%) to 76.5% (± 10.4%), difference 37.0% (95% CI, 33.5%--40.6%). Bag-mask ventilation and intraosseous insertion skills remained above baseline at 6-month follow-up. CONCLUSIONS: Simulation training is beneficial for teaching PALS procedures to family medicine residents.

Detection of elemental mercury in abdominal wall soft tissue.

CASE REPORT: A 19-year-old male with an unremarkable medical history presented with his father, who requested an evaluation of a pathology specimen from a reported "lump" under the skin in the middle of the son's lower abdomen. The lump had been excised by a surgeon approximately 3 months prior, per parental request. Upon gross inspection, the specimen appeared to contain small metallic droplets. The patient denied self-injection of any metals, including mercury, despite the results of a 24-hour urine heavy-metal screen (without chelation) that revealed an elevated concentration of mercury (87.6 microg/g creatinine; reference range for nonexposed adults: <4 microg/g creatinine). Confirmatory analysis of the tissue sample included gross and microscopic examination, electron microscopy using secondary and backscattered electron imaging modes, and energy dispersive x-ray spectrum analysis of isolated tissue particles. Grossly, the tissue had small silver spherules suggestive of elemental mercury; these droplets were identified histologically with associated foreign body reaction. Numerous smooth, round-to-oval particles scattered randomly throughout the tissue were identified ultrastructurally, which produced an x-ray energy spectrum corresponding to mercury. DISCUSSION: Elemental mercury is liquid at room temperature and may be injected into the body for recreational, psychiatric, and other purposes. Isolated cases of mercury injection following accidents with broken thermometers have been reported, as well as cases of elevated metallothionein concentration following human gingival amalgam tattoos. CONCLUSION: In cases of surreptitious injection, histology and ultrastructural evidence may be used to confirm the presence of mercury.

Evaluation of a novel Web-based pediatric advanced life support course.

OBJECTIVE: To assess the educational efficacy of a Web-based pediatric advanced life support course (Web-PALS). DESIGN: Nonrandomized, prospective, cohort study. SETTING: University medical center. PARTICIPANTS: Health care providers (includes physicians, nurses, paramedics, and respiratory therapists) taking either the Web-PALS or a traditional PALS course (Trad-PALS). MAIN EXPOSURE: Web-PALS. MAIN OUTCOME MEASURES: Postcourse written examination scores and scored videotapes of students performing 5 PALS procedures were compared between study groups. Students completed precourse and postcourse questionnaires, rating on a 5-point Likert scale their self-confidence to perform PALS assessments and procedures. A structured, course satisfaction survey was given after students had taken the Web-PALS course. RESULTS: Eighty-six students completed the study (44 Web-PALS and 42 Trad-PALS). All students achieved a passing score on the written examination on their first attempt. Compared with students in the Trad-PALS group, students in the Web-PALS group scored slightly lower (97.1% vs 95.4%; difference, 1.7%; 95% confidence interval, 0.1-3.2). Mean overall videotape scores were similar among the Web-PALS and Trad-PALS groups (75.0% vs 73.0%; difference, 2.0%; 95% confidence interval, -2.0 to 6.0). After completing the Web-PALS course, the mean level of confidence improved from 3.77 to 4.28 (difference, 0.51; 95% confidence interval, 0.33-0.69). Ninety-six percent of respondents indicated that Web-PALS met all of the stated objectives of the PALS course. All respondents indicated that they would recommend Web-PALS to a colleague. CONCLUSIONS: Students perceive Web-PALS as a positive educational experience. Though not identical to students taking the Trad-PALS course, they performed well on postcourse cognitive and psychomotor testing. These findings support Web-PALS as an acceptable format for administering the PALS course.

Amanita bisporigera ingestion: mistaken identity, dose-related toxicity, and improvement despite severe hepatotoxicity.

Ingestion of wild mushrooms has led to unintentional poisonings caused by mistaken identity. We report 3 cases of exposure to Amanita bisporigera, demonstrating dose-related toxicity. The use of nasobiliary drainage as a novel approach to interrupting the enterohepatic circulation of amatoxins is illustrated. Pathophysiology and treatment of Amanita poisoning are reviewed.

Unusual presentation of iatrogenic phenytoin toxicity in a newborn.

BACKGROUND: Medication errors may produce severe toxicity resulting in hospitalization. This can be compounded if the physician obtains the wrong concentration from a reference manual and a pharmacy miscalculates the conversion. We report a child presenting with ileus, hypothermia and lethargy after receiving supratherapeutic dosing of phenytoin after a concentration miscalculation. CASE REPORT: A one-month-old infant presented to the Emergency Department with progressive worsening of abdominal distension, diminished activity, and a one day history of difficulty feeding secondary to a decreased level of consciousness. The past medical history was significant for neonatal Group B Strep meningitis with seizures. Among the child's discharge medications was a prescription for phenytoin (30 mg/5 mL) 2.5 cc by mouth three times daily. On exam, the child was hypothermic with pink mottled skin, poor responsiveness, prolonged capillary refill, abdominal distension with hypoactive bowel sounds, and a dysconjugate gaze. The Initial phenytoin serum concentration was 91.8 mcg/mL. She was admitted to the PICU and was started on ampicillin and cefotaxime for R/O sepsis. Phenytoin was withheld and subsequent serum concentrations revealed an extremely slow elimination (mcg/mL vs. time pair coordinates were 78.2/13.3h; 74.3/62.3h; 43.7/109.6h; 10.8/160.9h) reflecting zero-order kinetics. Post discontinuing antibiotics, phenytoin levels decreased at rates expected. She was discharged after resolution of symptoms. The MD who had written the phenytoin prescription had based it on the Harriet Lane Handbook, 2000 Ed. The 30 mg/5 mL formulation has been unavailable in the US for several years. A community pharmacy substituted the 125 mg/5 mL formulation, but miscalculated the dosage to be 1.6 cc (40 mg) tid. CONCLUSIONS: Abdominal distension and ileus may be presenting symptoms in children at toxic phenytoin levels. Ampicillin and cefotaxime may effect the elimination rate of phenytoin at such levels. We report one of the highest phenytoin levels recorded after therapeutic misadventure. Physicians must be aware of inaccuracies in reference manuals that may result in dosing errors.

Pediatric orogastric and nasogastric tubes: a new formula evaluated.

STUDY OBJECTIVE: We sought to compare the traditional method of determining depth of gastric tube insertion, by measuring from the external landmarks of the nose or mouth, to the earlobe, to the xiphoid process (NEX method), with a graph for determining depth of gastric tube insertion that is based on patient height (graphic method). METHODS: A prospective, randomized, double-blinded study comparing NEX and graphic methods for gastric tube depth of insertion was undertaken. This study included a convenience sample of pediatric emergency department patients in need of gastric intubation. Patients were block randomized, and their gastric tubes were placed to the depth derived from the particular method employed. Alternate depth of insertion was measured on all patients. Abdominal radiographs were used to determine the distance that the end of the tube was from the center of the stomach. RESULTS: Forty-four patients each were in the NEX and graphic groups. The mean distance from the center of the stomach was -1.12 cm (SD 1.36) for the graphic group, compared with 1.31 cm (SD 3.39) for the NEX method. The difference between the 2 methods was 2.43 cm (95% confidence interval [CI] 1.33 to 3.54). Using absolute values, the mean distance from the center of the stomach was 1.26 cm (SD 1.23) for the graphic group compared with 2.60 cm (SD 2.51) for the NEX method. Using these values, the difference between the groups is 1.34 cm (95% CI 0.50 to 2.18). CONCLUSION: When compared with the NEX method, the graphic method demonstrates a significant ability to more consistently and accurately determine the depth of pediatric gastric tube insertion.