Effect of antidotes of the acute toxicity of methacrylonitrile

Summary When rats were exposed for 30 min to methacrylonitrile at concentrations between 3180 and 5700 ppm, the clinical symptoms observed suggested a toxic activity of metabolically formed cyanide. This is in contrast to the signs of toxicity observed in the same species after inhalation of acrylonitrile where metabolic cyanide formation plays only a minor role. The acute toxicity of methacrylonitrile could be antagonized with cyanide antidotes (4-dimethylaminophenol plus sodium thiosulfate) as well as with N-acetyl-cysteine which directly reacts with ,-unsaturated nitriles.     

Antagonistic effects against single lethal doses of Amanita phalloides

Summary Agents with antagonistic effects against phalloidin or -amanitin were tested in mice against lethal doses of an extract from the whole mushroom amanita phalloides. The following categories of agents reduced lethality after the extract. First, agents protecting only against phalloidin such as rifampicin, phenylbutazone and antamanide. Second, silymarin and prednisolone which display both antiamatoxic and marked (silymarin) or moderate (prednisolone) antiphallotoxic activity. Thioctic acid displayed some activity when tested against mid-lethal doses of the extract. Cytochrome c, a chemical with curative potencies against -amanitin did not reduce the lethality of the extract. All of the effective agents acted only when applied prior to the poisoning. The pattern or protective activity would indicate that in mice death after single doses of Amanita phalloides may follow a qualitatively particular course which is difficult to ascribe to phallo- or amatoxic effects alone.     

Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report

Introduction

The purpose of this study is to describe a case where methylene blue improved hemodynamics in a poisoned patient.

Case Report

This is a single case report where a poisoned patient developed vasodilatory shock following ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple therapies including vasopressors, high-dose insulin, hemodialysis, and 20% intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was administered in the ICU with temporal improvement as measured by pulmonary artery catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h of methylene blue administration, systemic vascular resistance improved (240 dyn s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with maintenance of mean arterial pressure 60 mmHg.

Discussion

Methylene blue may improve hemodynamics in drug-induced vasodilatory shock and should be considered in critically ill patients poisoned with vasodilatory medications refractory to standard therapies.     

False-Positive Amphetamine Screen Following a Trazodone Overdose

An 80-year-old diabetic patient was admitted to the hospital because of sudden unconsciousness and severe metabolic acidosis. His son reported the possibility of cyanide poisoning. Clinical data and the detection of cyanide in blood and gastric material confirmed this possibility. Supportive therapy and the following antidotes—sodium nitrite two doses 300 mg IV, sodium thiosulfate 3 g IV, and hydroxocobalamin 4 g in 24 hours—were administered immediately and the patient completely recovered in 48 hours. Our observations suggest that timely and appropriate use of antidotes for cyanide intoxication may prevent death, even in aged diabetic patients.     

Acute poisoning with gold cyanide

A case of deliberate ingestion of an electroplating solution containing gold cyanide is described. Despite the use of an antidote, and supportive treatment for cyanide poisoning, the patient died after 13 hours. Sublethal cyanide and high red blood cell gold levels suggest acute gold toxicity as the most likely cause of death. Evidence for this is discussed and recommendations are made for the treatment of cyanide poisoning.     

Attenuation of soman-induced lesions of skeletal muscle by acetylcholinesterase reactivating and non-reactivating antidotes

Summary It has been reported recently that some oximes reactivating acetylcholinesterase (AChE) exhibit concomitant ganglion-blocking effects which presumably could contribute independently to their powerfull antidotal action in organophosphate inhibitor (OPI) poisoning, thus mimicking some unrelated substances which are effective antidotes without reactivating AChE. This raises the question whether OPI-induced muscle lesions, like some other sympfoms could also be attenuated by oximes and other antidotes in the absence of AChE reactivation. To test this possibility, the oxime HI-6 was applied at increasing time intervals after the injection of soman until and beyond the point when soman-AchE complex becomes completely aged and not capable of reactivation. As the examples of OPI antidotes which do not reactivate AChE, the muscarinic antagonist atropine and the ganglion-blocking agent hexamethonium were also tested on possible attenuation of muscle lesions. The proportions of fibers with lesions, AChE inhibition and muscle fasciculations in expertmental groups relative to the controls treated with soman only were evaluated. The results show that HI-6 can attenuate lesions only if AChE is partially reactivated and muscle fasciculations are permanently climinated. However, atropine does not affect either AChE inhibition or muscle fasciculations and is also ineffective in counteracting the lesions in spite of its potency as an effective general antidote. Hexamethonium also does not affect AChE inhibition, but abolishes fasciculations and effectively attenuates muscle lesions. The latter findings reveal the existence of lesion-protecting mechanisms unrelated to AChE reactivation, which if further elucidated might become potentially relevant for additional treatment in OPI poisoning.Supported by a grant from the Research Community of Slovenia     

Prolonged Laboratory Interference After Administration of Intravenous Lipid Emulsion Therapy

Background

Pancreatitis and laboratory interference are rarely reported complications of intravenous lipid emulsion (ILE) therapy. We report a case of significant laboratory interference after ILE administration.

Case Report

A 43-year-old female was admitted to the hospital after an unwitnessed ingestion of propranolol, tramadol, zolpidem, and alprazolam. She was intubated and treated with intravenous normal saline, insulin/glucose, and norepinephrine infusions due to hypotension. Two bolus doses and one maintenance dose of 20 % ILE were administered. Beginning approximately 2 h after ILE administration, laboratory assays were unable to be performed due to the presence of lipemia. The patient developed refractory hypotension and was transferred to a tertiary care center. Upon admission to the ICU, the patient received one additional bolus of 20 % ILE. Laboratory assays were again attempted but were unable to be adequately performed due to a pinkish-white discoloration of the patient’s blood. Percutaneous femoral extracorporeal membrane oxygenation (ECMO) was initiated, but laboratory interference noted with the arterial blood gas analyzer prevented the analysis of oxygenation. The patient’s hemodynamic condition did not improve; she expired 31 h after initial admission.

Case Discussion

In one previous report, centrifugation was effective in removing more than 90 % of glycerol-banked triglycerides, thus minimizing lipid interference with laboratory assays. We noted persistent laboratory interference for more than 20 h after ILE administration, despite ultracentrifugation of specimens.

Conclusion

Clinicians should be aware that ILE administration may cause significant and prolonged interference with laboratory assays, which may affect the monitoring of critically ill patients.     

Cholestatic liver injury as a side-effect of dabigatran and the use of coagulation tests in dabigatran intoxication and after reversal by idarucizumab in bleeding and sepsis

Idarucizumab, an antidote specific for dabigatran, became available recently. Dabigatran is not associated with increased risk of hepatotoxicity in comparison with warfarin, but it is seen as a rare side-effect. Cases of cholestatic liver injury due to dabigatran have not been reported previously. We present a case of severe gastro-intestinal bleeding with underlying dabigatran intoxication in a patient with renal failure and the effect of reversal of dabigatran using idaruzicumab on coagulation assays. International normalized ratio (INR) and activated partial thromboplastin time (APTT) results were elevated in a setting of sepsis, possibly due to liver failure. INR and APTT can be elevated if sepsis is complicated by disseminated intravascular coagulation (DIC) or liver failure, making it challenging to determine dabigatrans contribution to their prolongation. A rebound effect after administration of idarucizumab and slow elimination of dabigatran due to reduced kidney function could be detected using the Hemoclot^® diluted thrombin time (dTT) in this situation, in contrast to with non-dilutional assays. Before admission, cholestatic liver injury started shortly after initiation of dabigatran etexilate therapy. As no other cause was found, this liver injury was likely to be drug-induced. Bleeding cessated promptly after administration of idarucizumab in dabigatran intoxication. In conclusion, the anticoagulant effect of dabigatran can be measured by Hemoclot^® dTT in sepsis and cholestatic liver injury was seen as a possible rare side-effect of dabigatran treatment.