Clinical toxicology : the official journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists
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Clin Toxicol (Phila) · Apr 2020
Incomplete responses to the recommended dose of idarucizumab: a systematic review and pharmacokinetic analysis.
Introduction: Dabigatran, a direct thrombin inhibitor, is 80% renally eliminated and demonstrates multi-compartmental pharmacokinetics. Idarucizumab is a monoclonal antibody that reverses dabigatran-induced anticoagulation and displays single compartment pharmacokinetics, with a smaller volume of distribution and shorter elimination half-life than dabigatran. These differences in pharmacokinetics mean that redistribution of dabigatran from peripheral compartments can occur after idarucizumab has been eliminated, resulting in rebound in the dabigatran plasma concentration and treatment failure. ⋯ If a rebound in dabigatran is noted, then repeat administration of idarucizumab 5 g can be considered for reversal of recurrent coagulopathy if clinically indicated. Conclusion: The use of idarucizumab for reversal of dabigatran is complex and requires consideration of clinical circumstances and laboratory investigations. Monitoring post-idarucizumab may be required in acute or chronic kidney disease to detect a rebound in dabigatran concentration and the need for additional doses of idarucizumab.
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Clin Toxicol (Phila) · Apr 2020
Case ReportsRebound metabolic acidosis following intentional amygdalin supplement overdose.
Introduction: Amygdalin, marketed misleadingly as supplement "Vitamin B17," is a cyanogenic glycoside. When swallowed, it is hydrolyzed into cyanide in the small intestine, which causes histotoxic hypoxia via inhibition of cytochrome c oxidase. It remains available for purchase online despite a ban from the US Food and Drug Administration. ⋯ Discussion: Our case demonstrates rebound metabolic acidosis after massive amygdalin overdose. Toxicity was associated with prolonged QTc, which warrants further investigation into clinical significance. Redosing of combination antidotal therapy suggested efficacy without adverse effects.
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Clin Toxicol (Phila) · Apr 2020
Reduced-dose intramuscular ketamine for severe agitation in an academic emergency department.
Introduction: Rapid sedation of severely agitated patients is often necessary to ensure the safety of patients and healthcare workers. Intramuscular (IM) ketamine 4-6 mg/kg was previously studied but may carry an increased risk of intubation and other adverse effects. Therefore, the purpose of this case series was to describe the efficacy and safety of a reduced-dose (2 mg/kg) IM ketamine guideline. ⋯ The median total dose administered was 157.5 mg and the median weight-based dose was 2 mg/kg. In 11 of the 15 cases, reduced-dose ketamine was used as a second-line agent. Conclusion: Reduced-dose IM ketamine may be effective for severe agitation, particularly when used as a second-line agent.