Intravenous pyridoxine-induced metabolic acidosis.

STUDY OBJECTIVE: Pyridoxine hydrochloride, the antidote for isonicotinic acid hydrazide (INH)--induced seizures, is available in solution at a concentration of 100 mg/mL at a pH of less than 3. Pyridoxine is often infused rapidly in large doses for INH-induced seizures. Effects of pyridoxine infusion on base deficit in amounts given for INH poisoning have not been studied in human subjects. We hypothesized that this infusion would result in transient worsening of acidosis. METHODS: We conducted a randomized, controlled crossover trial in human volunteers. Five healthy volunteers (mean age, 35 years; range, 29 to 43 years) were randomized to receive intravenous placebo (50 mL of normal saline solution) or 5 g of pyridoxine (50 mL) over 5 minutes. A peripheral intravenous catheter was established in each arm, and a heparinized venous blood sample was obtained for base deficit at baseline and 3, 6, 10, 20, and 30 minutes after infusion. After at least a 1-week washout period, the volunteers were assigned to the alternate arms of the experiments, thus acting as their own control subjects. Data were analyzed by using the 2-tailed paired t test, controlling for multiple comparisons. RESULTS: No difference was noted between groups at baseline. A statistically significant increased base deficit was noted after the pyridoxine infusion versus control at 3 to 20 minutes but not at 30 minutes (P =.1). Maximal mean increase in base deficit (2.74 mEq/L) was noted at 3 minutes. CONCLUSION: A transient increase in base deficit occurs after the infusion of 5 g of pyridoxine in normal volunteers.

Rattlesnake envenomations: unusual case presentations.

Rattlesnake envenomations are common in some areas of the United States. Although fatal rattlesnake envenomations are rare and usually preventable, morbidity may be significant. Patients may present with localized edema, hypotension, coagulopathy, or thrombocytopenia. Patients with progressive swelling or severe coagulopathy are typically treated with Crotalidae polyvalent antivenin. We present a series of 4 patients with unusual complications of rattlesnake envenomation to illustrate the wide spectrum of disease that may be encountered. These case presentations include anaphylaxis to rattlesnake venom, an acute airway emergency, progressive and marked edema with a large pleural fluid collection, and death.

Hypertonic sodium bicarbonate is effective in the acute management of verapamil toxicity in a swine model.

STUDY OBJECTIVE: This study was conducted to determine whether hypertonic sodium bicarbonate would improve the hypotension associated with severe verapamil toxicity compared with volume expansion. METHODS: The study design used a nonblinded acute animal preparation. Twenty-four anesthetized and instrumented swine were poisoned with verapamil delivered at a rate of 1 mg/kg per hour for 10 minutes followed by incremental increases of 1 mg/kg per hour every 10 minutes until the endpoint of a mean arterial blood pressure of 45% of baseline was achieved. Animals alternately received either 4 mEq/kg of hypertonic sodium bicarbonate intravenously over 4 minutes or similar volumes of 0.6% sodium chloride in 10% mannitol (control). The main outcome parameter followed was mean arterial pressure. In addition, physiologic parameters including cardiac output, heart rate, pH, PCO (2), PO (2), plasma ionized calcium, sodium, and potassium were monitored. RESULTS: Verapamil toxicity, as defined by a mean arterial pressure of 45% of baseline, was produced in all animals following an average verapamil infusion dose of 0.6+/-0.12 mg/kg. This dose produced an average plasma verapamil concentration of 728.1+/-155.4 microgram/L, with no significant difference between groups. Swine treated with hypertonic sodium bicarbonate experienced a significant increase in mean arterial pressure (>50%) and cardiac output (>30%) over the first 20 minutes that slowly equilibrated with the control group over the remainder of the experiment. As expected, plasma sodium concentrations were elevated significantly in the sodium bicarbonate group while plasma potassium concentrations were decreased significantly. Finally, there was a significant decrease in plasma ionized calcium concentration in the sodium bicarbonate-treated group compared with controls. CONCLUSION: Hypertonic sodium bicarbonate reversed the hypotension and cardiac output depression of severe verapamil toxicity in a swine model.

New drugs of abuse.

Newer drugs of abuse, such as MDMA, GHB, GBL, 1,4-BD and ketamine, are frequently used in the settings of raves and are often promoted on the internet. The popularity of these agents is increasing; therefore, emergency physicians should become familiar with the clinical presentations and management of the toxicity induced by these agents.

Crack cocaine ingestion with prolonged toxicity requiring electrical pacing.

CASE REPORT: We report a 38-year-old man who experienced prolonged toxicity lasting over 16 hours from the time of ingestion of 1/4 ounce of crack cocaine. His illness included status epilepticus, wide and narrow complex bradyarrhythmias, ventricular arrhythmias, and delayed hyperthermia. His bradyarrhythmias were refractory to medicinal intervention and responsive to application of an external pacemaker. The patient recovered to his baseline state over the ensuing 48 hours.

The lack of transplacental movement of the cyanide antidote thiosulfate in gravid ewes.

UNLABELLED: A previous study reported that the co-infusion of IV sodium thiosulfate (STS) with sodium nitroprusside (SNP) to near-term gravid ewes prevented both maternal and fetal cyanide toxicity. We questioned whether maternally administered STS crossed the ovine placenta to enhance fetal transulfuration of cyanide, or whether the fetus was dependent on maternal detoxification of cyanide after diffusion of cyanide into the maternal circulation. Ten anesthetized, near-term gravid ewes underwent hysterotomies with delivery of fetal heads for venous catheterization. Five control ewes received IV isotonic sodium chloride solution, whereas five experimental ewes received IV STS (50 mg/kg over 15 min). Serial plasma thiosulfate concentrations in ewes and fetuses were measured over 135 min. Areas under the time-plasma thiosulfate concentration curves were calculated for experimental and control ewes at 2758+/-197 and 508+/-74 min x mg(-1) x L(-1), respectively (P < 0.008). Mean areas under the curve for experimental and control fetuses were 236+/-34 and 265+/-23 min x mg(-1) x L(-1), respectively (P > 0.5). Maternally administered STS may prevent fetal cyanide poisoning from SNP administration without relying on STS crossing the placenta into the fetal circulation. Fetal cyanide may cross down a concentration gradient from fetal to maternal circulation, to be transulfurated to thiocyanate in maternal tissues. IMPLICATIONS: We evaluated the mechanism of action of sodium thiosulfide (STS) in sodium nitroprusside-induced cyanide toxicity in the ewe. Fetal cyanide poisoning is alleviated by maternal administration of STS, although this cyanide antidote apparently does not cross the placenta.

Heavy metal toxicity, part II: lead and metal fume fever.

This review is the second of a two-part review of heavy metal toxicity. This part will identify the salient features of the toxicopathophysiology, clinical presentation, and emergency department management of lead toxicity and metal fume fever.

Heavy metal toxicity, Part I: arsenic and mercury.

This review is Part I of a two-part series focusing on heavy metal toxicity. Part I will cover arsenic and mercury toxicity. Acute and chronic arsenic toxicity, as well as arsine gas toxicity, will be reviewed. The clinical presentation, with focus on the nervous, cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematopoietic, and dermatologic systems, is delineated. Mercury exposure, including exposure to short chain alkyl mercury, elemental mercury, and acute inorganic salt, is reviewed. The discussion of clinical toxicity focuses on the nervous, cardiovascular, pulmonary, gastrointestinal, and renal systems, as well as on the teratogenic effects of mercury. Recommendations for diagnostic tests and management plans are discussed, including chelation regimens.

The extremities and spine.

A variety of pearls, pitfalls, and updates related to the extremities and spine are discussed. Tricks of the trade regarding shoulder dislocations, easily missed fractures, radial head subluxation, and the approach to deep lacerations are discussed. In the pitfall section, potential difficulties in the evaluation of suspected nonaccidental trauma, compartment syndromes, partial cord syndromes, and hip pain in children are discussed. Finally, new information regarding cost-effective evaluation of knee and ankle injuries, as well as advances in ultrasound evaluation of shoulder and extremity injuries, is presented in the clinical updates section.

Antibiotic use in the emergency department. II The aminoglycosides, macrolides, tetracyclines, sulfa drugs, and urinary antiseptics.

The aminoglycoside, macrolide, tetracycline, and sulfa classes of antibiotics provide antimicrobial coverage pertinent to many infectious diseases diagnosed in the emergency department (ED). The aminoglycosides are parenteral agents that are useful in Gram-negative infections and as synergistic drugs in the management of some Gram-positive infections. The macrolides, of which erythromycin is the prototype, are used for a number of Gram-positive and atypical bacterial infections, while the tetracyclines are appropriate for ED treatment of a diverse group of infections such as chlamydiae, spirochetes, and rickettsiae. The sulfa agents are appropriate for many urinary and respiratory tract infections, and also have particular utility in some infections encountered primarily in patients with AIDS. The urinary antiseptics are a group of antimicrobials that may be effective for cystitis but have no systemic efficacy. This article, which is the second in a four-part series on antibiotic use in the ED, reviews the pharmacology and clinical utility of these diverse agents for the emergency physician.

Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells.

High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant approximately equal to 1.0 nM) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells. Of the steroids tested, only testosterone exhibited significant cross-reactivity with estrogen binding. RNA blot analysis with a complementary DNA probe to the human estrogen receptor revealed putative receptor transcripts of 6 to 6.2 kilobases in both rat and human osteosarcoma cells. Type I procollagen and transforming growth factor-beta messenger RNA levels were enhanced in cultured human osteoblast-like cells treated with 1 nM estradiol. Thus, estrogen can act directly on osteoblasts by a receptor-mediated mechanism and thereby modulate the extracellular matrix and other proteins involved in the maintenance of skeletal mineralization and remodeling.