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Clinical Journal of the American... Sep 2023Poisoning occurs after exposure to any of a number of substances, including medicines, which can result in severe toxicity including death. The nephrologist may be...
Poisoning occurs after exposure to any of a number of substances, including medicines, which can result in severe toxicity including death. The nephrologist may be involved in poisonings that cause kidney disease and for targeted treatments. The overall approach to the poisoned patient involves the initial acute resuscitation and performing a risk assessment, whereby the exposure is considered in terms of the anticipated severity and in the context of the patient's status and treatments that may be required. Time-critical interventions such as gastrointestinal decontamination ( e.g. , activated charcoal) and antidotes are administered when indicated. The nephrologist is usually involved when elimination enhancement techniques are required, such as urine alkalinization or extracorporeal treatments. There is increasing data to guide decision making for the use of extracorporeal treatments in the poisoned patient. Principles to consider are clinical indications such as whether severe toxicity is present, anticipated, and/or will persist and whether the poison will be significantly removed by the extracorporeal treatment. Extracorporeal clearance is maximized for low-molecular weight drugs that are water soluble with minimal protein binding (<80%) and low endogenous clearance and volume of distribution. The dosage of some antidotes ( e.g. , N-acetylcysteine, ethanol, fomepizole) should be increased to maintain therapeutic concentrations once the extracorporeal treatment is initiated. To maximize the effect of an extracorporeal treatment, blood and effluent flows should be optimized, the filter with the largest surface area selected, and duration tailored to remove enough poison to reduce toxicity. Intermittent hemodialysis is recommended in most cases when an extracorporeal treatment is required because it is the most efficient, and continuous kidney replacement therapy is prescribed in some circumstances, particularly if intermittent hemodialysis is not readily available.
Topics: Humans; Antidotes; Charcoal; Acetylcysteine; Ethanol; Poisons; Poisoning
PubMed: 37097121
DOI: 10.2215/CJN.0000000000000057 -
Chemistry (Weinheim An Der Bergstrasse,... Jul 2023Intoxication is one of the most common causes of accidental death globally. Although some antidotes capable of neutralizing the toxicity of certain xenobiotics have...
Intoxication is one of the most common causes of accidental death globally. Although some antidotes capable of neutralizing the toxicity of certain xenobiotics have become well established, the current reality is that clinicians primarily rely on nonspecific extracorporeal techniques to remove toxins. Nano-intervention strategies in which nanoantidotes neutralize toxicity in situ via physical interaction, chemical bonding, or biomimetic clearance have begun to show clinical potential. However, most nanoantidotes remain in the proof-of-concept stage, and the difficulty of constructing clinical relevance models and the unclear pharmacokinetics of nanoantidotes hinder their translation to clinic. This Concept reviews the detoxification mechanisms of polymer nanoantidotes and predicts the opportunities and challenges associated with their clinical application.
Topics: Polymers; Antidotes; Toxins, Biological; Biomimetics
PubMed: 37335074
DOI: 10.1002/chem.202301107 -
European Journal of Emergency Medicine... Oct 2023An increasing number of patients presenting to the emergency department (ED) with life-threatening bleeding are using oral anticoagulants, such as warfarin, Factor IIa...
An increasing number of patients presenting to the emergency department (ED) with life-threatening bleeding are using oral anticoagulants, such as warfarin, Factor IIa and Factor Xa inhibitors. Achieving rapid and controlled haemostasis is critically important to save the patient's life. This multidisciplinary consensus paper provides a systematic and pragmatic approach to the management of anticoagulated patients with severe bleeding at the ED. Repletion and reversal management of the specific anticoagulants is described in detail. For patients on vitamin K antagonists, the administration of vitamin K and repletion of clotting factors with four-factor prothrombin complex concentrate provides real-time ability to stop the bleeding. For patients using a direct oral anticoagulant, specific antidotes are necessary to reverse the anticoagulative effect. For patients receiving the thrombin inhibitor dabigatran, treatment with idarucizamab has been demonstrated to reverse the hypocoagulable state. For patients receiving a factor Xa inhibitor (apixaban or rivaroxaban), andexanet alfa is the indicated antidote in patients with major bleeding. Lastly, specific treatment strategies are discussed in patients using anticoagulants with major traumatic bleeding, intracranial haemorrhage or gastrointestinal bleeding.
Topics: Humans; Hemorrhage; Anticoagulants; Blood Coagulation; Rivaroxaban; Factor Xa Inhibitors; Emergency Service, Hospital; Vitamin K; Administration, Oral; Recombinant Proteins; Antidotes
PubMed: 37427548
DOI: 10.1097/MEJ.0000000000001049