William Banner

Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds.

The usefulness of N-acetylcysteine (NAC) as a chelating agent was studied for the toxin potassium dichromate, lead tetraacetate, and boric acid. Mature Sprague-Dawley rats were intoxicated with these substances and placed in metabolic cages. Urinary excretion rates of intoxicant and total urine volume were determined during treatment with N-acetylcysteine, calcium EDTA, and/or dimercaptosuccinic acid, N-acetylcysteine proved to be the most effective agent at increasing the excretion of chromium and boron and was also able to reverse the oliguria associated with these toxins. Dimercaptosuccinic acid was most effective at the chelation of lead. NAC did not increase the excretion of lead. We conclude that NAC may be useful in intoxications due to chromate and borate and is effective at reversing the oliguria associated with these intoxicants.

Treatment of acute methylmercury ingestion by hemodialysis with N-acetylcysteine (Mucomyst) infusion and 2,3-dimercaptopropane sulfonate.

A case of acute methylmercury ingestion was treated sequentially with oral D-penicillamine, hemodialysis during N-acetylcysteine (NAC) infusion, and 2,3-dimercaptopropane sulfonate (DMPS) an experimental oral agent. Urinary organic mercury elimination rate increased almost 40-fold during and 84-fold after hemodialysis with NAC infusion, compared with elimination during initial D-penicillamine therapy. Mean clearance during hemodialysis was only 13 ml/min with an extraction rate of 3.7 mcg/min. Although whole blood mercury concentrations decreased from 568 to 265 ng/ml during dialysis, a rebound to 525 ng/ml occurred. A total of 1.6 mg mercury was renally eliminated during hemodialysis and in the following 24 hours. A total of 3.3 mg of predominantly organic mercury was renally eliminated during 18 days of combined therapies. Since renal elimination of inorganic mercury is seen with chronic methylmercury poisoning, the high ratio of organic to inorganic mercury in urine supports the acute nature of this exposure. DMPS was begun on day 4 and during the two weeks of administration whole blood concentrations fell by 15% to 355 ng/ml. An expected decrease in elimination half-life to 10 days was not observed during DMPS therapy, possibly due to concurrent administration of vitamins containing zinc and copper. The amount of methylmercury ingested was estimated as 45 mg, based on a post-distribution blood concentration of approximately 450 ng/ml. The patient developed no symptoms of methylmercury poisoning during the one year after the episode. We conclude that NAC may be useful to enhance renal elimination of methylmercury and merits further investigation as a potential binding agent to reduce the body burden of methylmercury.

Anticholinergic Poisonings Associated with Commercial Burdock Root Tea

AbstractA case of anticholinergic poisoning associated with the consumption of a commerical burdock root tea preparation and confirmed by laboratory analysis in Arizona is reported.A second case of burdock root tea poisoning, confirmed by laboratory determination, has been described. The patient experienced mild anticholinergic symptoms which were caused by an atropine contaminant in the commercial preparation. The estimated dose of atropine involved in this case is 2.28 mg; the usual adult oral dose for antispasmodic activity is 0.3 to 1.2 mg.5 The importance of this finding is evident in the differential diagnosis of any anticholinergic poisoning. Common sources of such toxic symptoms from acute poisoning include phenothiazines, tricyclic antidepressants, and antihistamines. We have been unable to unequivocally ascertain whether the source of atropine in this preparation was the result of contamination from root or vegetable material of some other plant. This discovery of atropine in a commercially avai...

Failure of dialysis therapy in potassium dichromate poisoning

A fatal case of oral ingestion of potassium dichromate is presented. Following an initial presentation of abdominal pain and vomiting, the patient had a rapid progression to coma with the development of methemoglobinemia, coagulopathy, gastrointestinal hemorrhage, and respiratory distress syndrome. A blood concentration of chromium on admission was 5,800 mcg/dL, 80% of which was found to be in the intracellular fraction. Supportive treatment was also initiated as a four-hour period of hemodialysis followed by a one-hour period of charcoal hemoperfusion. Neither of these treatment modalities was found to significantly remove chromium from whole blood and neither seemed to affect the progression or outcome of this intoxication. We conclude that the ingestion of potassium dichromate is highly toxic and may rapidly lead to death. Hemodialysis and charcoal hemoperfusion appear to have little role in the management of chromium intoxication.

Systemic toxicity following gasoline aspiration

The major cause of mortality and morbidity associated with the ingestion of aliphatic hydrocarbon products is related to pulmonary aspiration. Despite the high frequency of the ingestions, there is little documentation of nonpulmonary toxic effects of petroleum distillates. Two cases of gasoline aspiration/ingestion that resulted in probable intravascular hemolysis are reported. In one of these cases, the patient also manifested a consumptive coagulopathy, acute renal failure and elevation of transaminase enzymes. With modern intensive pulmonary care, the outlook for patients with petroleum distillate aspiration is good, but any documented extrapulmonary manifestations of this condition may be important in the overall management of these patients.

Risks of Extracorporeal Membrane Oxygenation: Is there a Role for Use in the Management of the Acutely Poisoned Patient?

OBJECTIVE To review the use of extracorporeal membrane oxygenation in the support of poisoned patients and provide a basis for comparison to other methods of respiratory support for these patients. METHODS The medical literature was reviewed and selected cases of poisoning supported by extracorporeal membrane oxygenation and mechanical ventilation highlighted. Data from published outcome studies were reviewed. All cases found were included in the database. Case experiences were critiqued based on available clinical literature. Outcome studies were critiqued with respect to relevancy and bias. Many cases do not provide strong evidence of direct patient benefit. There are no data to support an improvement in outcome among poisoned patients. CONCLUSION The use of extracorporeal membrane oxygenation for respiratory failure following ingestion has the same limited indications as for other patients with respiratory failure. Data supporting an improvement in outcome are not available. Extracorporeal membrane oxygenation support for reversible cardiac toxicity has a sound basis but clinical experience is limited. Good supportive care for the poisoned patient is essential before considering extracorporeal membrane oxygenation.

The Effects of Esmolol on the Hemodynamics of Acute Theophylline Toxicity

The effects of esmolol, a beta 1-selective adrenergic receptor antagonist with a short duration of action, were studied in a canine model of the hemodynamics of theophylline toxicity. Animals were anesthetized, then given 50 mg/kg aminophylline IV over 20 minutes followed by a continuous infusion of 1.75 mg/kg/hr. Hemodynamic parameters, including heart rate, cardiac output, systemic blood pressure, pulmonary arterial pressure, and pulmonary artery wedge pressure, were measured every 30 minutes along with plasma catecholamines and theophylline levels. Marked tachycardia was seen in the intoxicated state, with heart rate rising from a baseline of 128.0 +/- 8.3 beats per minute (BPM) to 179.0 +/- 7.4 BPM (P = .012). This was associated with increases in catecholamines (baseline norepinephrine .04 +/- .04 ng/mL plasma rose to .42 +/- .21 ng/mL plasma after intoxication, P = .048). The average serum theophylline level during the experiment was 44.0 +/- 1.1 micrograms/mL serum. Esmolol then was given by IV infusion in these animals in doses of 25, 50, and 100 micrograms/kg/min. It returned the heart rate to the preintoxication baseline in a dose-related manner. Esmolol did not decrease cardiac output or lower blood pressure.

Clinical Toxicology in the Neonatal Intensive Care Unit

SummaryThe role of the clinical toxicologist in the neonatal nursery may be an extremely important one in the evaluation of epidemic-like toxic reactions occurring from: (a) the inappropriate use of medications; (b) the accidental contamination of parenterals; and (c) the introduction of relatively new products into the nursery environment.The newborn with high respiratory demands, thin epidermis with a large surface area to body mass ratio, and nutritional support being derived completely from parenteral sources provides a great number of routes of entry for the introduction of toxins. In approaching these problems, the clinician needs a structured approach in considering the impact of the route of administration, the contents of the product and the ability of the newborn to eliminate the toxin in question.In addition, some knowledge of the specialised structures and diseases of the newborn is required to adequately analyse the impact of a potential toxin on newborn disease processes. What we normally consider as adverse drug reactions are extremely rare in the neonate. Hypersensitivity phenomenon and the classic non-dose-related side effects described in adults are rare occurrences. This makes it a challenge for the clinical toxicologist to analyse and attempt to identify a toxic substance in the nursery.Having identified a toxin in the newborn, treatment may be complicated by the inability to use many of the standard forms of therapy, e.g. activated charcoal, diuresis, and extracorporeal removal The lack of practicality of these procedures increases the necessity for good supportive care. Exchange transfusion, rarely considered in older children and adults, may offer the only viable option for rapid removal of a drug.

Effects of single large doses of phenytoin on glucose homeostasis--a preliminary report.

Abstract: The effects of a loading dose of 15 mg/kg phenytoin by iv infusion on the serum levels of insulin, glucagon, and glucose were investigated in five fasting healthy male volunteers between the ages of 23 and 35 years. Serum glucose concentrations rose immediately after the infusion of phenytoin followed by a significant increase in serum insulin values (P < 0.05). A slight elevation in mean glucagon concentrations after the infusion was not statistically significant. Further studies are indicated to determine whether phenytoin as used in the treatment of status epilepticus may aggravate the hyperglycemia associated with seizures.

Lack of specific (3H) prazosin binding sites in dog and rabbit cerebral arteries

In order to explore the characteristics of alpha adrenergic receptors on cerebrovascular smooth muscle, specific binding sites for the alpha 1 adrenergic ligand, (3H) prazosin, were studied in blood vessel homogenates. No specific (3H) prazosin binding was found in either rabbit or dog cerebral arteries, but specific binding was demonstrated in the rabbit saphenous and ear arteries. In the ear artery 3H-prazosin binding was saturable with a Kd of 0.51 +/- 0.20 nM and a Bmax of 89 +/- 29 fmoles/mg protein. To confirm the adequacy of our membrane preparation, homogenates of both dog and rabbit cerebral arteries showed saturable specific binding with two different ligands: one for muscarinic receptors, [3H](-) quinuclidinyl benzilate (QNB) and one for alpha 2 adrenergic receptors, (3H) yohimbine. The results of these studies demonstrate a lack of alpha 1 adrenergic receptors on cerebral blood vessels, confirming functional studies showing only a weak contractile response to norepinephrine.