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Critical Care Medicine Jun 2015
Topics: Antidotes; Humans; Methanol; Renal Dialysis
PubMed: 25978175
DOI: 10.1097/CCM.0000000000001006 -
Clinical Toxicology (Philadelphia, Pa.) Jul 2022Thiocyanate can cause gastrointestinal, neurologic, and cardiovascular toxicity. Additionally, it interferes with multiple laboratory assays. We present a case of acute...
Thiocyanate can cause gastrointestinal, neurologic, and cardiovascular toxicity. Additionally, it interferes with multiple laboratory assays. We present a case of acute thiocyanate toxicity. A 17-year-old female presented with an intentional thiocyanate ingestion. Her course was notable for delirium, wide complex tachycardia, and presumed seizure activity with concurrent lactatemia, acidemia, and narrowing of her arterio-venous oxygen gradient. She received lipid emulsion therapy (LET). While hemodialysis was considered, she recovered without additional treatment. After resolution of her critical illness, a serum cyanide concentration was 0.21 mcg/mL. She had laboratory testing notable for hyperchloremia, hypocalcemia, hypokalemia, and an elevated salicylate concentration attributed to interference by thiocyanate. The thiocyanate was eliminated via first-order kinetics with a half-life of 61.6 hours. Thiocyanate poisoning may cause cardiac and neurologic toxicity. Laboratory evidence of impaired cellular respiration in this case suggests possible in vivo conversion to cyanide, however this is not proven. Cyanide antidotal treatment was not administered for this patient, however LET was given based on thiocyanate's lipophilicity. Hemodialysis is known to effectively remove thiocyanate from the blood, however the patient improved without it. The patient's laboratory derangements were due to thiocyanate interference with ion selective electrode and colorimetric analyzer technology. Thiocyanate can cause cardiac and neurologic toxicity, and interferes with several laboratory assays. Theoretically, LET and cyanide antidotal treatment may be useful, but this requires further investigation. Thiocyanate toxicity should be managed supportively, and hemodialysis may be used in severe cases.
Topics: Acidosis; Adolescent; Antidotes; Cyanides; Female; Humans; Thiocyanates
PubMed: 35240906
DOI: 10.1080/15563650.2022.2042012 -
Thrombosis Research May 2024Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or... (Review)
Review
Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.
Topics: Humans; Antidotes; Anticoagulants; Administration, Oral; Factor Xa Inhibitors; Drug Monitoring; Recombinant Proteins; Factor Xa; Antibodies, Monoclonal, Humanized
PubMed: 38626592
DOI: 10.1016/j.thromres.2024.04.005 -
British Journal of Anaesthesia Feb 2024This study in vitro comprehensively assessed reversal of the anticoagulant effects of rivaroxaban, an oral factor Xa inhibitor, using andexanet alfa and various...
This study in vitro comprehensively assessed reversal of the anticoagulant effects of rivaroxaban, an oral factor Xa inhibitor, using andexanet alfa and various prothrombin complex concentrate (PCC) products in a battery of tests. In static coagulation assays, andexanet alpha outperformed PCCs except for activated PCC being more effective in standard coagulation times. However, in a flow chamber model mimicking arterial shear, both andexanet alpha and high-concentration PCC restored fibrin formation, but not platelet adhesion. In the Russell's viper venom test and anti-Xa assay, only andexanet alpha could be tested for efficacy. The antidote effects of andexanet alpha and PCCs in restoring coagulation can be qualitatively or selectively demonstrated using in vitro coagulation tests.
Topics: Humans; Factor Xa Inhibitors; Antidotes; Blood Coagulation Factors; Rivaroxaban; Factor IX; Recombinant Proteins; Anticoagulants; Factor Xa
PubMed: 38071150
DOI: 10.1016/j.bja.2023.11.028 -
Science Translational Medicine Jun 2015The number of intoxications from xenobiotics--natural or synthetic foreign chemicals, or substances given in higher doses than typically present in humans--has risen... (Review)
Review
The number of intoxications from xenobiotics--natural or synthetic foreign chemicals, or substances given in higher doses than typically present in humans--has risen tremendously in the last decade, placing poisoning as the leading external cause of death in the United States. This epidemic has fostered the development of antidotal nanomedicines, which we call "nano-antidotes," capable of efficiently neutralizing offending compounds in situ. Although prototype nano-antidotes have shown efficacy in proof-of-concept studies, the gap to clinical translation can only be filled if issues such as the clinical relevance of intoxication models and the safety profile of nano-antidotes are properly addressed. As the unmet medical needs in resuscitative care call for better treatments, this Perspective critically reviews the recent progress in antidotal medicine and emerging nanotechnologies.
Topics: Antidotes; Drug Overdose; Humans; Nanotechnology; Poisoning
PubMed: 26041703
DOI: 10.1126/scitranslmed.3008736 -
Emergency Medicine Australasia : EMA Feb 2021Poisoned patients commonly present to EDs. The optimal management of these patients is constantly evolving as new evidence emerges. Textbooks cannot be updated regularly... (Review)
Review
Poisoned patients commonly present to EDs. The optimal management of these patients is constantly evolving as new evidence emerges. Textbooks cannot be updated regularly enough to incorporate these changes, and their advice may not reflect the current practice of experts. Clinicians treating poisoned patients need an up-to-date accessible resource to aid their management decisions. The updated eTG complete, Toxicology and Toxinology guideline represents a consensus of contemporary evidence and expert views from across Australia. Important key changes include: updated advice on decontamination, particularly use of activated charcoal; stepwise escalation in supportive care, including guidance on the most appropriate inotropes for each agent and antidote recommendations for specific poisoning scenarios. Toxicology and Toxinology covers more than 100 poisoning topics and offers more detailed risk assessment, management and disposition advice. It is a valuable evidence-based resource for the management of poisoned patients.
Topics: Antidotes; Australia; Charcoal; Evidence-Based Medicine; Humans; Poisoning; Risk Assessment; Toxicology
PubMed: 33124195
DOI: 10.1111/1742-6723.13663 -
PloS One 2022Antidote stocking represents a major challenge to hospitals all over the world, including Kuwait. In order to assist hospitals to reduce costs and improve patient care,...
Antidote stocking represents a major challenge to hospitals all over the world, including Kuwait. In order to assist hospitals to reduce costs and improve patient care, an essential antidote list can be used as an initial foundation for securing sufficient antidote availability at healthcare institutions. The aim of our study is to generate a nationally relevant essential antidote list for emergency care hospitals in Kuwait using the e-Delphi method by establishing consensus through a multidisciplinary expert group of healthcare providers. An electronic survey with 47 essential antidotes was developed. The e-Delphi method was used, with three rounds of voting, to determine expert consensus on an essential antidote list for hospitals in Kuwait. A purposive sample of healthcare professionals from governmental and private hospitals were selected for this study (n = 30). Consensus was gained if ≥75% of the expert panel agreed on the inclusion of the antidote, without any strong disagreements. Round 1 of the e-Delphi resulted in 41 antidotes reaching consensus and seven new antidotes suggested by the expert panel. Round 2 had two antidotes (out of seven newly suggested ones) reaching consensus. Round 3 was a confirmatory round, where the expert group agreed on their previous rounds' opinions. This resulted in the development of an essential antidote list with 43 antidotes. The optimal approach for ensuring adequate availability of antidotes is continuous monitoring of local poisoning incidence and antidote requirements through collaborations between academic researchers and emergency care clinicians. The development of an essential antidote list, with expert consensus, is one of the initial steps in securing a foundation for appropriate provision of antidotes at all healthcare institutions. This is the first study that the authors are aware of that demonstrates that the e-Delphi technique can consolidate recommendations of experts in emergency medicine to provide a list of essential antidotes.
Topics: Antidotes; Consensus; Delphi Technique; Emergency Medical Services; Humans; Pharmacy Service, Hospital
PubMed: 35709136
DOI: 10.1371/journal.pone.0269456 -
Clinical Toxicology (Philadelphia, Pa.) Feb 2018Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed. (Review)
Review
BACKGROUND
Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed.
OBJECTIVES
To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium.
METHODS
A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI's), and p values.
RESULTS
Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non-diphenhydramine antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n = 3) had 100% response to physostigmine, whereas anticholinergic plants (n = 46/67; 68.7%, OR: 0.70; CI: 0.36-1.35), diphenhydramine (n = 43/56; 64.2%, OR: 1.30; CI: 0.63-2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30-7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED).
DISCUSSION
Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6 h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED.
CONCLUSIONS
In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2 mg.
Topics: Antidotes; Cholinergic Antagonists; Cholinesterase Inhibitors; Delirium; Humans; Physostigmine; Retrospective Studies
PubMed: 28703024
DOI: 10.1080/15563650.2017.1342828 -
Journal of Biochemical and Molecular... May 2017Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without... (Review)
Review
Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without immediate medical intervention. Current therapies mitigate the cholinergic crisis caused by nerve agents but do not fully prevent long-term health concerns, for example, brain damage following seizures. Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger being investigated as an antidote for OP nerve agent poisoning. HuBChE sequesters OP nerve agent in the bloodstream preventing the nerve agent from reaching critical target organ systems. HuBChE was effective when used as both a pre-treatment and as a post-exposure therapy. HuBChE has potential for use in both military settings and to protect civilian first responders in situations where nerve agent usage is suspected. We reviewed various animal models studies evaluating the efficacy of HuBChE against nerve agent exposure, pursuant to its submission for approval under the FDA Animal Rule.
Topics: Animals; Antidotes; Butyrylcholinesterase; Humans; Nerve Agents
PubMed: 28225154
DOI: 10.1002/jbt.21886 -
Toxicology Nov 2014Potent cholinesterase inhibitors such as sarin, induce an array of harmful effects including hypersecretion, convulsions and ultimately death. Surviving subjects... (Review)
Review
Potent cholinesterase inhibitors such as sarin, induce an array of harmful effects including hypersecretion, convulsions and ultimately death. Surviving subjects demonstrate damage in specific brain regions that lead to cognitive and neurological dysfunctions. An early accumulation of acetylcholine in the synaptic clefts was suggested as the trigger of a sequence of neurochemical events such as an excessive outpour of glutamate and activation of its receptors. Indeed, alterations in NMDA and AMPA central receptors' densities were detected in brains of poisoned animals. Attempts to improve the current cholinergic-based treatment by adding potent anticonvulsants or antiglutamatergic drugs produced unsatisfactory results. In light of recent events in Syria and the probability of various scenarios of military or terrorist attacks involving organophosphate (OP) nerve agent, research should focus on finding markedly improved countermeasures. Caramiphen, an antimuscarinic drug with antiglutamatergic and GABAergic facilitating properties, was evaluated in a wide range of animals and experimental protocols against OP poisoning. Its remarkable efficacy against OP exposure was established both in prophylactic and post-exposure therapies in both small and large animals. The present review will highlight the outstanding neuroprotective effect of caramiphen as the optimal candidate for the treatment of OP-exposed subjects.
Topics: Acetylcholine; Animals; Antidotes; Brain; Chemical Warfare Agents; Cholinesterase Inhibitors; Cyclopentanes; Humans; Neuroprotective Agents; Organophosphate Poisoning
PubMed: 25201353
DOI: 10.1016/j.tox.2014.09.005