Sean Patrick Nordt

Midazolam: A review of therapeutic uses and toxicity

Midazolam is a familiar agent commonly used in the emergency department to provide sedation prior to procedures such as laceration repair and reduction of dislocations. Midazolam is also effective in the treatment of generalized seizures, status epilepticus, and behavioral emergencies, particularly when intravenous access is not available. Midazolam is often employed as an induction agent for rapid sequence endotracheal intubation. Midazolam has a rapid onset of action following intravenous, intramuscular, oral, nasal, and rectal administration. Only 50% of an orally administered dose reaches the systemic circulation due to extensive first-pass metabolism. Midazolam is metabolized by the cytochrome P450 enzyme system to several metabolites including an active metabolite, alpha-hydroxymidazolam. Cytochrome P450 inhibitors such as cimetidine can profoundly reduce the metabolism of midazolam. Midazolam has a half-life of approximately 1 h, but this half-life may be prolonged in patients with renal or hepatic dysfunction. Midazolam has been associated with respiratory depression and cardiac arrest when used in combination with an opioid, particularly in the elderly, although all ages are at risk for respiratory depression. Midazolam is relatively free of side effects when used alone and offers several advantages over traditional pharmacological agents such as chloral hydrate and the combination of meperidine, chlorpromazine, and promethazine. Hiccups, cough, nausea, and vomiting are the most commonly reported adverse effects. Many of the adverse effects associated with midazolam can be reversed rapidly by the administration of flumazenil, a competitive benzodiazepine receptor antagonist. Midazolam is a safe and effective agent for providing sedation in the emergency department.

Prospective Evaluation of Mild to Moderate Pediatric Acetaminophen Exposures

STUDY OBJECTIVE To determine whether pediatric patients with acute, mild to moderate acetaminophen exposures, treated with home monitoring alone, develop systemic signs of hepatic injury. METHODS A prospective, observational study of calls to a regional poison center over a 25-month period was performed. Patients were eligible for the study if they were younger than 7 years and had an acute maximum possible acetaminophen exposure of up to 200 mg/kg. Exclusion criteria included previous decontamination measures, possibility of ingestion of an extended-release preparation, health or medication issues that could increase susceptibility to hepatotoxicity, current symptoms of hepatotoxicity, and indeterminable ingestions. Study protocol included reviewing the signs and symptoms of early and late acetaminophen toxicity, a 4- to 6-hour follow-up call, and a 72-hour follow-up call. Outcome measures were defined as a verbal report by the patients parent or guardian of the presence or absence of signs or symptoms of hepatotoxicity. RESULTS A total of 1,039 patients were enrolled in the study, including 519 girls and 520 boys, with exposures ranging from 20 to 200 mg/kg. Eighteen patients were lost to follow-up; data were incomplete for 2 patients. At 72-hour follow-up, the remaining 1,019 patients were all doing well, without signs or symptoms of hepatotoxicity. CONCLUSION On the basis of these data, pediatric patients with acute acetaminophen exposures of up to 200 mg/kg, treated with home monitoring alone, do not develop signs or symptoms of hepatic injury.

Successful Treatment of Crotalid-Induced Neurotoxicity With a New Polyspecific Crotalid Fab Antivenom

STUDY OBJECTIVE To report the effectiveness of a new polyvalent crotalid antivenom on neurotoxicity associated with North American rattlesnake envenomation. Two syndromes of crotalid-induced neurotoxicity have been reported. In severe envenomation by Crotalus scutulatus scutulatus (Mojave rattlesnake), weakness and fasciculations of various muscle groups, including those innervated by cranial nerves, may develop. Occasionally respiratory insufficiency develops. The second neurotoxic effects is myokymia, a type of fasciculation most frequently reported after bites by Crotalus horridus horridus (timber rattlesnake) and Crotalus atrox (Western diamondback rattlesnake). Conventional polyvalent antivenom is often ineffective in the treatment of venom-induced neurotoxicity. METHODS We report a case series of three patients envenomated by North American rattlesnakes, one of which was identified as C scutulatus scutulatus. All three patients experienced neurotoxicity with weakness, paresthesias, and dramatic fasciculations, along with other signs and symptoms of crotalid venom poisoning. RESULTS The administration of new polyspecific crotalid antivenom made of ovine Fab was successful in immediately and completely reversing neurotoxicity in each of these patients. CONCLUSION We report the use of a new antivenom for North American crotalid envenomation that seems to have efficacy in reversing neurotoxicity associated with these bites.

Clarithromycin-induced ventricular tachycardia

Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug.

ACUTE LINDANE POISONING IN THREE CHILDREN

Lindane has been reported to cause central nervous system (CNS) toxicity including seizures after prolonged dermal contact and also after acute ingestions. Despite safer alternatives, lindane still remains a commonly used agent in the treatment of scabies and pediculosis. We present three cases of acute toxicity after the inadvertent oral administration of lindane in three siblings. A 17-month-old female suffered a single seizure. A 3-year-old male was listless, nauseated, pale, and had decreased responsiveness to verbal and tactile stimulation. A 4-year-old female became nauseated and required bag-valve-mask ventilation for hypoventilation. The three patients all recovered without sequelae.

Association of rattlesnake bite location with severity of clinical manifestations.

STUDY OBJECTIVE To examine an association between bite location in cases of North American crotalid envenomation and the severity of clinical manifestations. METHODS We conducted a retrospective review of prospectively collected data for an experimental trial of crotalid antivenom. Our subjects were otherwise healthy individuals with minimal to moderate North American crotalid envenomation. We compared the severity of envenomation for patients with digit bites distal to the proximal interphalangeal joint and bites more proximal using a previously developed and validated snakebite severity score. RESULTS Thirteen subjects were classified as having distal bites and 24 as having proximal bites. At baseline (before antivenom administration), the distal group had a mean severity score of 2.9 +/- 1.1, whereas the proximal group had a mean severity score of 5.0 +/- 2.2 (P = .0024). Patients in the proximal group tended to demonstrate a more rapid initial decline in severity score after receiving antivenom than did the distal group. CONCLUSION In minimal to moderate North America crotalid envenomation, patients who sustained bites on distal aspects the digits tended to experience less severe clinical manifestations of envenomation. It is possible that an isolated bite to the distal aspect of a finger is an early marker of minimal envenomation.

Hypermagnesemia Following an Acute Ingestion of Epsom Salt in a Patient with Normal Renal Function

CASE REPORT Hypermagnesemia is a rare condition that commonly follows excessive therapeutic administration of magnesium sulfate to treat eclampsia of pregnancy. Signs and symptoms of this condition include extreme muscle weakness, loss of deep tendon reflexes, mental status depression, and cardiac dysrhythmias. Clinically significant hypermagnesemia following oral or rectal administration of magnesium containing products in patients with normal renal function is rare. We report a case of hypermagnesemia following massive Epsom salt ingestion that resulted in extreme musculoskeletal weakness and altered mentation.

Resource-Use Analysis of a Medical Toxicology Consultation Service

STUDY OBJECTIVE To evaluate the impact of a medical toxicology consulting service (MTCS) on resource use and efficiency of care in patients hospitalized with a diagnosis of tricyclic antidepressant (TCA) poisoning. METHODS We conducted a retrospective, case-controlled medical-records review at two urban tertiary care teaching hospitals. The study population comprised patients who presented to the emergency department with a diagnosis of TCA poisoning, in two phases. The first phase was longitudinal; we evaluated cases over 4 years before and after inception of an MTCS at one institution. In the second phase we compared consecutive cases of TCA poisoning treated at two urban teaching hospitals located within a mile of each other with similar patient populations, one with and one without MTCS backup. Inclusion criteria consisted of complete medical records, ingestion of first- and second-generation TCAs, and age greater than 16 years. Patients were excluded if history, physical examination, or laboratory analysis suggested that multiple substances had been ingested. Extensive demographic data were collected in each case. Clinical information obtained from each patient included admission vital signs, pupil size, QRS and corrected QT duration, and the presence of markers of severe TCA toxicity such as hypotension, seizures, pulmonary edema, respiratory insufficiency necessitating intubation, and the occurrence of antimuscarinic signs and symptoms. Information regarding treatment was also collected from each case, including laboratory tests, decontamination procedures, administration of sodium bicarbonate, and use of other medications and therapies. RESULTS We identified a total of 88 patients in both phases of the study. Comparison groups were similar with respect to age, sex, presenting vital signs, presenting QRS and corrected QT duration, and incidence of recorded antimuscarinic signs, hypotension, seizures, and respiratory insufficiency requiring intubation. Total length of stay in a monitored hospital bed was also similar between groups. One fatality was recorded, but all other patients were discharged home or to a psychiatric facility. Patients seen by the MTCS consumed fewer health care resources in the form of less decontamination and fewer laboratory tests. CONCLUSION The MTCS may provide a resource-efficient means of treating patients with TCA poisoning. A larger, multicenter study of a variety of poisoned patients should be undertaken to further investigate this issue.

Comparison of Three Aspirin Formulations in Human Volunteers

Introduction The treatment of acute coronary syndrome (ACS) includes the administration of aspirin. Current guidelines recommend chewing aspirin tablets to increase absorption. While this is intuitive, there are scant data supporting this recommendation. The purpose of this study is to assess which of 3 different aspirin formulations is most rapidly absorbed after ingestion. Methods A prospective, open-label, 3-way crossover volunteer study at a tertiary university medical center with human subjects 18 years or older. Fasted subjects were randomly assigned to receive aspirin 1,950 mg as (1) solid aspirin tablets swallowed whole, (2) solid aspirin tablet chewed then swallowed, or (3) a chewable aspirin formulation chewed and swallowed. Serum salicylate measurements were obtained over a period of 180 minutes. Pharmacokinetic parameters were determined. Results Thirteen males and 1 female completed all 3 arms of study. Peak serum salicylate concentrations were seen at 180 minutes in all groups. Mean peaks were 10.4, 11.3, and 12.2 mg/dL in groups 1, 2, and 3, respectively. Mean area under the time concentration was 1,153, 1,401, and 1,743 mg-min/dL in groups 1, 2, and 3, respectively. No measurable salicylate concentrations were seen in 6 subjects in group 1 at 60 minutes as compared to 1 subject in group 2. All subjects in group 3 had measurable levels at 45 minutes. There were no adverse effects in any of the subjects during the study period. Conclusion Our data demonstrate that the chewable aspirin formulation achieved the most rapid rate of absorption. In addition, the chewable formulation absorption was more complete than the other formulations at 180 minutes. These data suggest that in the treatment of ACS, a chewable aspirin formulation may be preferable to solid tablet aspirin, either chewed or swallowed.

Death on the doorstep of a border community – intentional self-poisoning with veterinary pentobarbital

Introduction. “Suicide tourism,” the practice of traveling to a foreign destination to commit suicide, has been described in the medical literature. Additionally, committing suicide by self-administering veterinary medications has been previously described. Case Descriptions. We report two successful and one unsuccessful suicide attempts involving border-town travelers utilizing self-administered veterinary pentobarbital over a 1-year period. Discussion/Conclusion. Health care practitioners should be aware of and informed about this phenomenon.