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Current Reviews in Clinical and... 2021Poisoning is one of the leading causes of childhood morbidity and mortality worldwide. Despite the advancement of poison detection by modern investigation methods, the... (Review)
Review
BACKGROUND
Poisoning is one of the leading causes of childhood morbidity and mortality worldwide. Despite the advancement of poison detection by modern investigation methods, the clinical skill of toxidrome recognition by combining the findings from a detailed history, thorough physical examination, and the results of basic investigations is still indispensable for the management of children with suspected poisoning.
OBJECTIVE
The aim was to review pediatric toxidromes and poisoning management.
METHODS
A literature search was conducted on PubMed (between February 1 and 15, 2020) with keywords "toxidrome" "poisoning" "intoxication" "children" and "pediatric". The search was customized by applying the appropriate filters so as to get the most relevant articles to meet the objective of this review article.
RESULTS
Toxidrome recognition may offer a quick guide to possible toxicology diagnosis so that specific antidote can be administered in a timely manner. This article discusses a few commonly encountered toxidromes in pediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are also discussed. Although most patients with intoxication can be managed with close observation, supportive measures and antidote treatment, it is unfortunate that antidotes are only available for a limited number of poisons responsible for intoxication. Extracorporeal toxin removal is being increasingly recognized as a mode of treatment for patients with rapid deterioration who are unresponsive to conventional management. The decision to apply such technique and the choice of modality are frequently individualized due to the paucity of high-level evidence. The various patient and toxin/medication factors involved in the decision- making process are discussed.
CONCLUSION
Poisoning is a common cause of pediatric accidents and injuries. Physicians should be familiar with common toxidromes and poisoning management.
Topics: Antidotes; Child; Humans; Physical Examination; Poisons
PubMed: 33261543
DOI: 10.2174/1574884715666201201090210 -
Journal of Infusion Nursing : the... 2020To prepare clinicians to treat extravasation of noncytotoxic vesicants with antidotes and thermal compresses, a literature review was performed to identify noncytotoxic... (Review)
Review
To prepare clinicians to treat extravasation of noncytotoxic vesicants with antidotes and thermal compresses, a literature review was performed to identify noncytotoxic vesicants and to create evidence and consensus-based recommendations. The stage of injury and vesicant's mechanism of tissue injury dictate treatment. For a vasopressor extravasation, warm compresses and administration of a vasodilator are recommended. For osmolarity, pH, absorption refractory, and cytotoxic concentration-dependent vesicants, warm compresses and administration of hyaluronidase are recommended. Compared with potentially catastrophic costs of undertreatment, the cost of overtreatment is minimal.
Topics: Antidotes; Antineoplastic Agents; Extravasation of Diagnostic and Therapeutic Materials; Humans; Irritants
PubMed: 33141794
DOI: 10.1097/NAN.0000000000000392 -
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 -
Clinical and Applied... Jul 2017Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability,... (Review)
Review
Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4.5 to 10 in patients with other risk factors for bleeding. Fresh frozen plasma or prothrombin complex concentrate (PCC) may be necessary in major bleeding related to warfarin. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors. The PCC may reverse the effect of rivaroxaban to some extent, but no data are available regarding reversal of apixaban and edoxaban. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Blood Coagulation Factors; Blood Coagulation Tests; Hemorrhage; Humans; International Normalized Ratio; Plasma; Protamines
PubMed: 27789605
DOI: 10.1177/1076029616675970 -
Toxicology Letters Feb 2022Acetaminophen (paracetamol, APAP) poisoning is a prominent global cause of drug-induced liver injury. While N-acetylcysteine (NAC) is an effective antidote, it has... (Review)
Review
INTRODUCTION
Acetaminophen (paracetamol, APAP) poisoning is a prominent global cause of drug-induced liver injury. While N-acetylcysteine (NAC) is an effective antidote, it has therapeutic limitations in massive overdose or delayed presentation. The objective is to comprehensively review the literature on fomepizole as a potential adjunct antidote for acetaminophen toxicity.
METHODS
A scoping review was performed using standardized search terms from inception through July 2021.
RESULTS
Reports on fomepizole as a therapeutic adjunct for APAP toxicity span heterogeneous types of evidence. Eleven preclinical studies (in vitro and animal), fourteen case reports/series, and one human volunteer study were included. Fomepizole's action is mediated by inhibition of CYP2E1 to prevent oxidant stress generation, and inhibition of c-Jun N-terminal kinase (JNK) to decrease amplification of oxidant stress signaling to mitochondria. Studies have shown a reduction in oxidative metabolites likely by shunting metabolism away from CYP2E1 and a resultant decrease in liver injury in animals, independent of CYP2E1 interactions. Fomepizole has been linked to few adverse effects.
CONCLUSION
Based on in vitro and animal studies, and bolstered by case reports, fomepizole likely offers benefit as an adjunct antidote for APAP toxicity, however this remains to be shown in a human trial. NAC remains the standard of care antidote, but given that fomepizole is approved and generally safe, it may be considered for APAP toxicity as off-label use by experienced clinicians, in rare circumstances associated with increased risk of hepatotoxicity despite standard NAC dosing. The marginal clinical benefit of fomepizole adjunct therapy beyond NAC monotherapy remains to be clearly defined, and routine use for APAP overdose is premature based on current evidence.
Topics: Acetaminophen; Antidotes; Chemical and Drug Induced Liver Injury; Fomepizole; Humans
PubMed: 34785186
DOI: 10.1016/j.toxlet.2021.11.005 -
Annals of Emergency Medicine Mar 2018We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology,... (Review)
Review
We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for both the quantity of antidote that should be stocked and the acceptable timeframe for its delivery. The panel recommended consideration of 45 antidotes; 44 were recommended for stocking, of which 23 should be immediately available. In most hospitals, this timeframe requires that the antidote be stocked in a location that allows immediate availability. Another 14 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine its specific need for antidote stocking. Antidote administration is an important part of emergency care. These expert recommendations provide a tool for hospitals that offer emergency care to provide appropriate care of poisoned patients.
Topics: Antidotes; Consensus; Emergency Medical Services; Guidelines as Topic; Hospitals; Humans; Pharmacy Service, Hospital; Poisoning; Surveys and Questionnaires
PubMed: 28669553
DOI: 10.1016/j.annemergmed.2017.05.021 -
Journal of Medical Toxicology :... Apr 2019Cyanide, a metabolic poison, is a rising chemial threat and ingestion is the most common route of exposure. Terrorist organizations have threatened to attack the USA and... (Review)
Review
Cyanide, a metabolic poison, is a rising chemial threat and ingestion is the most common route of exposure. Terrorist organizations have threatened to attack the USA and international food and water supplies. The toxicokinetics and toxicodynamics of oral cyanide are unique, resulting in high-dose exposures, severe symptoms, and slower onset of symptoms. There are no FDA-approved therapies tested for oral cyanide ingestions and no approved intramuscular or oral therapies, which would be valuable in mass casualty settings. The aim of this review is to evaluate the risks of oral cyanide and its unique toxicokinetics, as well as address the lack of available rapid diagnostics and treatments for mass casualty events. We will also review current strategies for developing new therapies. A review of the literature using the PRISMA checklist detected 7284 articles, screened 1091, and included 59 articles or other reports. Articles referenced in this review were specific to risk, clinical presentation, diagnostics, current treatments, and developing therapies. Current diagnostics of cyanide exposure can take hours or days, which can delay treatment. Moreover, current therapies for cyanide poisoning are administered intravenously and are not specifically tested for oral exposures, which can result in higher cyanide doses and unique toxicodynamics. New therapies developed for oral cyanide exposures that are easily delivered, safe, and can be administered quickly by first responders in a mass casualty event are needed. Current research is aimed at identifying an antidote that is safe, effective, easy to administer, and has a rapid onset of action.
Topics: Administration, Oral; Antidotes; Cyanides; Humans; Mass Casualty Incidents; Poisoning; Risk; Terrorism; Toxicokinetics
PubMed: 30539383
DOI: 10.1007/s13181-018-0688-y -
Critical Care Nursing QuarterlyPoisoning, drug overdose, and adverse drug effects continue to be a common encounter, especially in the intensive care unit (ICU). Patients are often critically ill or...
Poisoning, drug overdose, and adverse drug effects continue to be a common encounter, especially in the intensive care unit (ICU). Patients are often critically ill or have a potential to rapidly deteriorate and warrant ICU admission. Adults suffering from overdoses rarely give a complete and accurate description of the quantity or type of medications ingested. In most adult cases, multiple substances are involved. A tentative diagnosis in most overdose and poisoning cases can be made by physical examination and simple laboratory tests (electrolyte panel, creatinine, serum osmolarity, urinalysis, etc). Supportive care, with particular attention to airway management, oxygenation, and circulation, is the mainstay of treatment. Basic treatment principles include limiting the amount of toxin absorbed, enhancing the elimination of ingested toxin, and preventing the conversion of non-toxic compounds to toxic metabolites. Drugs or poisons, where specific antidotes or effective therapies exist (especially acetaminophen, salicylates, methanol, ethylene glycol, and digitalis), should be aggressively sought and treated after initial stabilization has been accomplished. For those drugs or poisons where specific quantitative tests are available, levels should be obtained before treatment and may be repeated as clinically indicated.
Topics: Adult; Humans; Emergencies; Antidotes; Ethylene Glycol; Methanol; Poisons
PubMed: 36415069
DOI: 10.1097/CNQ.0000000000000439 -
Basic & Clinical Pharmacology &... Jan 2016Flumazenil is used for the reversal of benzodiazepine overdose. Serious adverse events (SAEs) including seizures and cardiac arrhythmias have been reported in patients... (Meta-Analysis)
Meta-Analysis Review
Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication--A Systematic Review with Meta-Analyses of Randomised Trials.
Flumazenil is used for the reversal of benzodiazepine overdose. Serious adverse events (SAEs) including seizures and cardiac arrhythmias have been reported in patients treated with flumazenil, and the clinical advantage of flumazenil treatment has been questioned. The objective was to assess the risk of (S)AEs associated with the use of flumazenil in patients with impaired consciousness due to known or suspected benzodiazepine overdose. Studies included in the meta-analyses were identified by literature search in Medline, Cochrane Library and Embase using combinations of the words flumazenil, benzodiazepines, anti-anxiety agents, poisoning, toxicity and overdose. Randomised clinical trials (RCTs) in verified or suspected benzodiazepine overdose patients comparing treatment with flumazenil versus placebo were included. Pre-defined outcome measures were AEs, SAEs and mortality. Thirteen trials with a total of 994 randomised (990 evaluable) patients were included. AEs were significantly more common in the flumazenil group (138/498) compared with the placebo group (47/492) (risk ratio: 2.85; 95% confidence interval: 2.11-3.84; p < 0.00001). SAEs were also significantly more common in the flumazenil group compared with the placebo group (12/498 versus 2/492; risk ratio: 3.81; 95% CI: 1.28-11.39; p = 0.02). The most common AEs in the flumazenil group were agitation and gastrointestinal symptoms, whereas the most common SAEs were supraventricular arrhythmia and convulsions. No patients died during the blinded phase of the RCTs. The use of flumazenil in a population admitted at the emergency department with known or suspected benzodiazepine intoxication is associated with a significantly increased risk of (S)AEs compared with placebo. Flumazenil should not be used routinely, and the harms and benefits should be considered carefully in every patient.
Topics: Antidotes; Benzodiazepines; Drug Overdose; Flumazenil; Humans; Randomized Controlled Trials as Topic; Receptors, GABA-A
PubMed: 26096314
DOI: 10.1111/bcpt.12434 -
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