Donna Seger

Clinical Presentation and Outcome of Brown Recluse Spider Bite

STUDY OBJECTIVE To examine the clinical presentation and outcome of patients treated in the ED or toxicology clinic for suspected brown recluse spider bites. METHODS We assembled a retrospective case of patients at a southeastern US university hospital. Our study group comprised 111 patients with suspected brown recluse spider bites treated during a 30-month period. Our main outcome measures were the need for skin grafting and the development of other complications. RESULTS The mean age of our subjects was 34 +/- 17 years. Thirteen patients (12%) brought the spider to the hospital, 22 (20%) saw a spider at the time of the bite, and an exclusively clinical diagnosis was made in the remaining 76 (68%). Most wounds (59%) involved the leg. At the time of presentation, 81% had central discoloration and 37% necrosis. Sixteen patients (14%) were systemically ill, and 6 (5%) were admitted to the hospital. Most (86%) were treated with antibiotics. Dapsone was infrequently used (9%) and had usually been prescribed before the patients presentation to our ED. Only three patients (3%; 95% confidence interval, 1% to 8%) required grafting. Mild hemolytic anemia developed in one patient, and another had mild hemolysis and a mild coagulopathy; neither patient was taking dapsone. No deaths or serious complications occurred in our study group. CONCLUSION In our series, long-term outcome after brown recluse spider bite was good. Serious complications were rare, as was the need for skin grafting. Because the vast majority of bites heal with supportive care alone, aggressive medical therapy does not appear warranted.

Carbon Monoxide Controversies: Neuropsychologic Testing, Mechanism of Toxicity, and Hyperbaric Oxygen

Recent animal and clinical data require a reevaluation of the traditional approach to the patient exposed to carbon monoxide. Unfortunately, these new data are inconclusive and generate controversies regarding the indications and value of neuropsychologic testing, cause of carbon monoxide toxicity, and indications (if any) for hyperbaric oxygen therapy. These controversies and their implications for the emergency physician are discussed.

Flumazenil—Treatment or Toxin

Flumazenil is frequently administered to the poisoned patient. Seizures may be precipitated and resedation may occur in patients who awakened following flumazenil administration. Seizures may increase morbidity and mortality of the overdose. Benefit: Risk ratio of administering flumazenil should be determined in each overdose patient. Indications for flumazenil are limited.

Clonidine toxicity revisited.

The incidence of clonidine overdose is increasing, yet there is a paucity of new information regarding treatment options for clonidine toxicity. Reported treatment approaches vary widely, demonstrating the lack of science on which current treatment is based. Available research needs to be reassessed. Neurotransmitters, receptors, endogenous opioids, and baseline sympathetic tone determine the clinical response to clonidine as well as the potential response to drug therapy following clonidine overdose. This article reviews aspects of clonidine toxicity that need to be further investigated. Multicenter research trials will be required to evaluate new treatment options.

Topiramate Overdose: Clinical and Laboratory Features

Limited data exist on overdose with new antiepileptic drugs. We reviewed the medical records of two patients who took a topiramate overdose as a suicide attempt. We recorded their medical and seizure histories, concomitant antiepileptic medications, neurologic examination, and laboratory findings at the time of presentation following the overdose. We also recorded their progress and the evolution of laboratory abnormalities. Both patients progressed to coma and had generalized convulsive status epilepticus, requiring intubation and treatment with benzodiazepines. Both patients recovered within 2 days but had a non-anion-gap metabolic acidosis that persisted for 5-6 days. Physicians should carefully monitor patients treated with topiramate who develop signs of clinical depression. The non-anion-gap metabolic acidosis observed may be due to inhibition of renal cortical carbonic anhydrase.

Cocaine, metamfetamine, and MDMA abuse: the role and clinical importance of neuroadaptation

Introduction. This article reviews the role and clinical importance of specific neuroadaptations that may occur following use of cocaine, metamfetamine, and 3,4,methylenedioxymetamfetamine (MDMA). Methods. A literature search was performed using OVID MEDLINE and PubMed for all years to the present date, which identified 250 papers of which 154 were considered relevant. Mechanisms of action of cocaine and metamfetamine. Cocaine and metamfetamine increase central nervous system synaptic dopamine primarily by increasing the release of dopamine into the synapse and binding to the dopamine reuptake transporter, which prevents the reuptake of dopamine from the synapse back into the nerve cell. Synaptic dopamine then stimulates post synaptic receptors. The continued release of dopamine and prevention of reuptake results in a supraphysiological concentration of dopamine, which causes euphoria or a “high.” The greater the concentration of dopamine, the greater the high. Continued supraphysiological concentrations of dopamine and postsynaptic receptor stimulation may cause physiological and anatomical changes (neuroadaptations) in the central nervous system (CNS) synapse that attempt to maintain homeostasis. An example of a dopaminergic neuroadaptation is the decrease in number of post synaptic D2 receptors that occurs when synaptic dopamine concentrations remain supraphysiological. This neuroadaptation attempts to maintain homeostasis, that is, the decreased number of D2 receptors provides fewer receptors to be constantly stimulated by increased synaptic dopamine. Although metamfetamine also increases synaptic dopamine similarly to cocaine, metamfetamine also increases cytoplasmic dopamine, which causes CNS oxidative stress and neurotoxicity. The clinical impact of the oxidative stress is unknown. Mechanisms of action of MDMA. MDMA increases concentrations of synaptic serotonin by increasing the release of serotonin and binding to the serotonin reuptake transporter, preventing the reuptake of serotonin from the synapse back into the nerve cell. An example of a serotonergic neuroadaptation is a decrease in the number of serotonin presynaptic autoreceptors (one of the regulators of synaptic serotonin concentration) to maintain homeostasis. MDMA also causes a decrease in serotonergic biochemical markers and neuronal axotomy in rats and nonhuman primates. Abstinence may allow reinnervation, but the axonal regrowth pattern is abnormal. Whether axotomy and reinnervation also occur in humans is unknown. Pharmacogenomics may play a role in the varied response of the individual to MDMA. Conclusions. Neuroadaptations may be transient or permanent. The duration of drug use or drug concentration needed to cause neuroadaptations is unknown, but some neuroadaptations begin shortly after initiation of drug use and are dependent on variables such as genetics and age at the initiation of use. Understanding the concept of neuroadaptation and some specific neuroadaptations that occur will allow clinicians to better understand the interindividual variability in response to drugs of abuse.

Hemolytic anemia following a presumptive brown recluse spider bite

This case report describes a systemic reaction occurring in a 12-year-old female following presumed envenomation by a brown recluse spider (Loxosceles reclusa). The systemic reaction included self-limited hemolysis necessitating blood transfusion. The clinical course and management are described and compared with those of previously reported cases of systemic loxoscelism.

Single‐Dose Activated Charcoal‐Backup and Reassess

Single‐dose activated charcoal (SDAC) is frequently administered to poisoned patients. The assumption is that toxin absorption is prevented and that toxicity (as defined by morbidity and mortality) of the poisoning is decreased. Yet there is no evidence that SDAC improves outcome. Risks of this procedure have not been determined. The reported adverse events following SDAC administration are reviewed and risk:benefit ratio for this procedure is discussed.

Hyperbaric oxygen for carbon monoxide poisoning: does it really work?

See related article, p 474. [Olson KR, Seger D: Hyperbaric oxygen for carbon monoxide poisoning: Does it really work? Ann Emerg Med April 1995;25:535-537.]

A Critical Reconsideration of the Clinical Effects and Treatment Recommendations for Sodium Channel Blocking Drug Cardiotoxicity

The cardiac sodium channel is comprised of proteins that span the cardiac cell membrane and form the channel pore. Depolarisation causes the proteins to move and open the sodium channel. Once the channel is open (active conformation), sodium ions move into the cell. The channel then changes from the active conformation to an inactive conformation — the channel remains open, but influx of sodium ions ceases. Recovery occurs as the channel moves from the inactive conformation back to the closed conformation and is then ready to open following the next depolarisation. Sodium channel blocking drugs (NCBDs) occupy receptors in the channel during the active and inactive conformations. The drug dissociates from most of the channel receptors during recovery, but the time it takes the drug to dissociate slows recovery. The slowed recovery prolongs conduction time, the main toxicity of NCBD overdose. Conduction time is further prolonged if heart rate increases as there are more available active and inactive conformations/unit time, which increases channel receptor binding sites for the NCBD. In addition to prolonging conduction time, NCBDs also decrease inotropy.Treatment of NCBD cardiotoxicity has been based on in vitro and animal experiments, and case reports. Assumptions based on this evidence must now be reassessed. For example, canines consistently develop ventricular tachycardia (VT) when tricyclic antidepressants (TCAs) are administered. Much of the literature discussing NCBD cardiotoxicity assumes that TCA poisoning induces VT in humans with the same regularity that occurs in canines. Seemingly, in support of this assumption was the finding that patients with remote myocardial infarction developed VT when therapeutically ingesting a NCBD. However, conduction is prolonged in myocardium that is or has been ischaemic. NCBD prolong conduction more in previously ischaemic myocardium than in normal myocardium, which causes nonuniform conduction and allows the development of re-entrant arrhythmias such as VT. Although some nonuniform conduction may occur in the healthy heart following a NCBD overdose, there is no evidence that nonuniform conduction occurs to the extent that it will cause re-entrant arrhythmias in this setting. Using various animal models and a variety of NCBDs, sodium ions, bicarbonate ions and alkalosis have been compared for the treatment of ventricular arrhythmias, hypotension and mortality. The results of these experiments have been extrapolated to NCBD overdose in humans.Animal models and single treatment approaches may have narrowed our scope. More recent evidence indicates that properties of each individual NCBD may require unique treatment. There is limited evidence that glucagon, which increases initial sodium ion influx into the cardiac cell, should be considered early in the treatment of cardiotoxicity. Another consideration may be treatment of NCBD with faster kinetics. Conduction time is decreased if a NCBD occupying the receptor is replaced by a NCBD that moves off and on the receptor more quickly. There is less evidence for this treatment, as risk may be greater. With greater understanding of the sodium channel and NCBDs, we must reassess our approach to the treatment of patients with healthy hearts who overdose on NCBD.