Nathan B. Menke

Complications Following Antidotal Use of Intravenous Lipid Emulsion Therapy

The primary objective is to identify and describe the complications associated with the use of intravenous lipid emulsion (ILE) therapy as an antidote for lipophilic drug toxicity. This study is a retrospective chart review of patients treated with ILE at two academic medical centers between 2005 and 2012. Based on previously reported complications, we hypothesized that pancreatitis, ARDS, and lipemia-induced laboratory interference might occur. Clinical definitions of these complications were defined a priori. Subjects treated with ILE who did not develop at least one complication were excluded. A total of nine patients were treated with ILE during the study period, six of whom experienced potential complications as a result of the ILE. Two patients developed pancreatitis, and four patients had lipemia-induced interference of interpretation of laboratory studies, despite ultracentrifugation. Laboratory interference precluded one patient from being an organ donor. Three patients developed ARDS; although temporally associated, a causal relationship between ILE and the development of ARDS cannot be clearly established. As ILE is increasingly used for less severe cases of drug toxicity, clinicians should be aware of potential complications associated with its use. A risk–benefit assessment for the use of ILE should be implemented on a case-by-case basis.

Prosthetic Hip-Associated Cobalt Toxicity

Prosthetic hip-associated cobalt toxicity (PHACT) is gaining recognition due to the use of metal-on-metal total hip replacements. Identifying true toxicity from merely elevated cobalt levels can be extremely difficult due to the lack of available data. An extensive review of the medical literature was undertaken to characterize cobalt toxicity from prosthetic hips. As an objective approach to making the diagnosis of PHACT, we suggest the following criteria: (1) elevated serum or whole blood cobalt levels due to a prosthetic hip, (2) at least two test-confirmed findings consistent with cobalt toxicity, and (3) exclusion of other etiologies. Adhering to objective diagnostic data for PHACT is a realistic and prudent method by which to eliminate the subjectivity of vague or difficult to identify complaints. These diagnostic criteria are not meant to evaluate prosthetic hardware failure, but as a means to identify systemic cobalt toxicity. Finally, assessment of cobalt toxicity from prosthetic hips should be done in conjunction with a medical toxicologist.

A retrospective analysis of the utility of an artificial neural network to predict ED volume.

OBJECTIVE The objectives of this study are to design an artificial neural network (ANN) and to test it retrospectively to determine if it may be used to predict emergency department (ED) volume. METHODS We conducted a retrospective review of patient registry data from February 4, 2007, to December 31, 2009, from an inner city, tertiary care hospital. We harvested data regarding weather, days of week, air quality, and special events to train the ANN. The ANN belongs to a class of neural networks called multilayer perceptrons. We designed an ANN composed of 37 input neurons, 22 hidden neurons, and 1 output neuron designed to predict the daily number of ED visits. The training method is a supervised backpropagation algorithm that uses mean squared error to minimize the average squared error between the ANNs output and the number of ED visits over all the example pairs. RESULTS A linear regression between the predicted and actual ED visits demonstrated an R2 of 0.957 with a slope of 0.997. Ninety-five percent of the time, the ANN was within 20 visits. CONCLUSION The results of this study show that a properly designed ANN is an effective tool that may be used to predict ED volume. The scatterplot demonstrates that the ANN is least predictive at the extreme ends of the spectrum suggesting that the ANN may be missing important variables. A properly calibrated ANN may have the potential to allow ED administrators to staff their units more appropriately in an effort to reduce patient wait times, decrease ED physician burnout rates, and increase the ability of caregivers to provide quality patient care. A prospective is needed to validate the utility of the ANN.

Re-Evaluating the Diagnostic Accuracy of the Tongue Blade Test: Still Useful as a Screening Tool for Mandibular Fractures?

BACKGROUND Mandibular fractures are one of the most frequently seen injuries in trauma. In terms of facial trauma, mandible fractures constitute 40%-62% of all facial bone fractures. The tongue blade test (TBT) has been shown to be a sensitive screening tool when compared with plain films. However, recent studies have demonstrated that computed tomography (CT) scan is more sensitive for determining mandible fractures than the traditionally used plain films. OBJECTIVE The purpose of the study was to determine the sensitivity and specificity of the TBT as compared with the new gold standard of radiologic imaging, CT scan. METHODS Any patient suffering from facial trauma was prospectively enrolled during the study period (August 1, 2010 to April 11, 2012) at a single urban, academic Emergency Department. A TBT was performed by the resident physician and confirmed by the supervising attending. CT facial bones were then obtained for the ultimate diagnosis. Inter-rater reliability (κ) was calculated, along with sensitivity, specificity, negative predictive value, and likelihood ratio (-) based on a 2 × 2 contingency table generated. RESULTS During the study period, 190 patients were enrolled. Inter-rater reliability was κ = 0.96 (95% confidence interval [CI] 0.93-0.99). The following parameters were then calculated based on the contingency table: sensitivity 0.95 (95% CI 0.88-0.98), specificity 0.68 (95% CI 0.57-0.77), negative predictive value 0.92 (95% CI 0.82-0.97), and likelihood ratio (-) 0.07 (95% CI 0.03-0.18). CONCLUSIONS Based on the test characteristics calculated (negative predictive value 0.92, sensitivity 0.95, likelihood ratio -0.07), the TBT is a useful screening tool to determine the need for radiologic imaging.

Nonfatal tramadol overdose may cause false-positive phencyclidine on Emit-II assay

False-positive results are a common finding with qualitative urine drug screens. This report describes 2 patients with positive phencyclidine (PCP) screens using the Emit II Plus Drugs-of-Abuse Test (Siemens Healthcare Diagnostics, Inc, Tarrytown, NY) after tramadol ingestion. Our first case was a 43-year-old woman with a history of bipolar disorder who presented to the emergency department(ED) for medical clearance after ingesting an unknown amount of tramadol. Her urine drugs-of-abuse screen was positive for PCP. A comprehensive gas chromatography/mass spectrometry qualitative urine drug screen demonstrated valproic acid metabolites, nicotine, gabapentin, benztropine, and a large peak of tramadol. Our second case was a 3-year-old boy with a medical history of previous ingestions presented to the ED for altered mental status and suspected ingestion. His urine drugs-of-abuse screen was positive for PCP. A comprehensive gas chromatography/mass spectrometry qualitative urine drug screen demonstrated a large peak of tramadol. Molecular similarity analysis can predict cross-reactivity of drug of abuse and therapeutic drug monitoring assays. This computational analysis demonstrated that tramadol and its metabolite possess enough similarity to PCP to produce positives due to interaction with the assay antibody (or antibodies). Tramadol and its metabolites can cause a false-positive Emit II+ PCP screen, and clinicians should use caution when interpreting urine drugs-of-abuse screens that use immunoassays.

A Patient With Alcoholic Ketoacidosis and Profound Lactemia

BACKGROUND Alcoholic ketoacidosis (AKA) is a complex syndrome that results from disrupted metabolism in the setting of excessive alcohol use and poor oral intake. Dehydration, glycogen depletion, high redox state, and release of stress hormones are the primary factors producing the characteristic anion gap metabolic acidosis with an elevated β-hydroxybutyrate (β-OH) and lactate. CASE REPORT We present the case of a 47-year-old man who presented to the emergency department with metabolic acidosis and profoundly elevated lactate levels who had AKA. He recovered completely with intravenous fluids and parenteral glucose administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should always consider the immediately life-threatening causes of a severe anion gap metabolic acidosis and treat aggressively based on the situation. This case highlights the fact that AKA can present with an impressively elevated lactate levels. Emergency physicians should keep AKA in the differential diagnosis of patients who present with a similar clinical picture.

Cardiotoxicodynamics: Toxicity of Cardiovascular Xenobiotics

Maintaining adequate tissue perfusion depends on a variety of factors, all of which can be influenced by xenobiotics (substances foreign to the body, including pharmaceuticals, chemicals, and natural compounds). Volume status, systemic vascular resistance, myocardial contractility, and cardiac rhythm all play a significant role in ensuring hemodynamic stability and proper cardiovascular function. Direct effects on the nervous system, the vasculature, or the heart itself as well as indirect metabolic effects may play a significant role in the development of cardiotoxicity. This article is dedicated to discussion of the disruption of cardiovascular physiology by xenobiotics.

Carbon Monoxide Poisoning Due to “Mud Bogging”

Mud bogging is a sport in which motor vehicles may become trapped in mud that clogs exhaust pipes. Four cases of carbon monoxide poisoning related to mud bogging are described.

Pygmy rattlesnake envenomation treated with Crotalidae Polyvalent Immune Fab Antivenom

UNLABELLED Documented envenomations by the pygmy rattlesnake (Sistrurus miliarius barbouri) are rare. While there have been no documented fatalities, several older case reports describe significant morbidity. We describe the first known case of pygmy rattlesnake envenomation that was treated with Crotalidae Polyvalent Immune Fab Antivenom (CroFab®). CASE A 28-year-old man with no significant past medical history presented after being envenomated on the right hand by his friends pet pygmy rattlesnake. He developed swelling and pain in his hand and forearm. He responded well to a ten vial loading dose and a 18 h maintenance protocol of CroFab and was discharged the following day without developing any hematological or electrolyte derangements. CONCLUSION This is the first documented use of CroFab for S. m. barbouri envenomation. The outcome of this case suggests that CroFab is a safe treatment modality in this setting.

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Background: Cyclodextrins (CD) are hydrophilic oligosaccharides that are widely used as excipients to increase drug solubility and stability but may also have utility in enhancing elimination and decreasing xenobiotic toxicity. Much like one of the proposed mechanisms of intralipid use, CD has the potential to create an intravascular sink. Sugammadex, a CD that effectively reverses the effects of rocuronium, exemplifies this mechanism of “detoxification.” A previous study undertaken by the same authors demonstrated worse survival times with administration of a sulfobutyether-beta-cyclodextrin (SBE-CD) to verapamil-poisoned rats. The authors attributed this effect to the cyclodextrin’s hyperosmolar load. Research Question: Does SBE-CD decrease time to death in a verapamil-poisoned rat model? Methods: This was a prospective, unblinded randomized, controlled study. After induction, male Wistar rats were infused with verapamil (32 mg/kg/h) and varying concentrations of SBE-CD premixed in the same infusion bag. A control group and four treatment groups were administered verapamil and SBE-CD with molar ratios of 1:1, 1:2, 1:4, and 1:8. Osmolarity varied between 300 and 352 mOsm/L. The primary endpoint was time to asystole. Results: Time to asystole was prolonged in the 1:4 ratio group when compared to control (21.2 vs. 17.6 minutes, p=0.05). No other intervention group demonstrated a statistically significant difference in time to asystole. There were no differences in time to apnea, but apnea preceeded arrest by several minutes in all groups. Conclusion: At a molar ratio of 1:4, a verapamil–SBE-CD infusion demonstrated statistically significantly increased time to asystole. Critique: Overall, this is an interesting but negative study. The lack of a dose response suggests that the SBE-CD was unlikely to be responsible for the increased time to asystole in the 1:4 group. As no power calculation was provided, the lack of efficacy may also be due to an inadequate number of subjects per group. Limitations include the premixing of verapamil and SBE-CD and co-infusion (an artificial model of human poisonings), lack of invasive hemodynamic monitoring, and apnea preceding cardiac arrest in all groups. Finally, as with all animal studies, the applicability to human physiology is unclear. Implication for Toxicologists: Intravascular sequestration of toxic xenobiotics is an intriguing mechanism for the potential treatment of many xenobiotics. Although mechanistically plausible, little weight can be placed on this potential intervention until further investigation supports improved outcomes.