Development of direct oral anticoagulants and their antidotes has led to the need to reconsider the eligibility of acute stroke patients who have been taking oral anticoagulants for intravenous thrombolysis. Officially authorized Japanese guidelines on this issue were revised twice at the time of approval for clinical use of direct oral anticoagulants and idarucizumab, a specific reversal agent for dabigatran. A unique recommendation in the latest Japanese clinical guides was that thrombolysis can be recommended if the time of the last dose of direct oral anticoagulants exceeds 4 hours and if commonly available anticoagulation markers are normal or subnormal, i.e., international normalized ratio of prothrombin time < 1.7 and activated partial thromboplastin time < 1.5 times the baseline value (≤40 seconds only as a guide). These criteria are partly supported by the findings of domestic multicenter and single-center surveys that symptomatic or asymptomatic intracranial hemorrhage following thrombolysis was rare under the conditions of the criteria. Even for dabigatran users, stroke thrombolysis can be considered without pretreatment by idarucizumab if patients meet the above criteria. If not, direct mechanical thrombectomy can be considered without pretreatment by idarucizumab or thrombolysis, and use of idarucizumab, followed immediately by thrombolysis, can be considered only when thrombectomy cannot be quickly performed. These clinical guides are practical and to some extent economical, but they have some limitations, including lack of corroborating information from sufficient numbers of relevant cases. The guides will be further modified based on the results of future research.
Anticoagulants ; Antidotes ; Asian Continental Ancestry Group ; Atrial Fibrillation ; Consensus* ; Dabigatran ; Humans ; International Normalized Ratio ; Intracranial Hemorrhages ; Japan* ; Partial Thromboplastin Time ; Prothrombin Time ; Stroke* ; Thrombectomy

PURPOSE: Glehnia littoralis has been reported to have several pharmacological properties but no in vivo reports describing the protective effects of this plant on α-amanitin-induced hepatotoxicity have been published. α-Amanitin is a peptide found in several mushroom species that accounts for the majority of severe mushroom poisonings leading to severe hepatonecrosis. In our previous in vitro study, we found that α-amanitin induced oxidative stress, which may contribute to its severe hepatotoxicity. The aim of this study was to investigate whether Glehnia littoralis acetate extract (GLEA) has protective antioxidant effects on α-amanitin-induced hepatotoxicity in a murine model. METHODS: Swiss mice (n=40 in all groups) were divided into four groups (n=10/group). Three hours after giving α-amanitin (0.6 mg/kg, i.p.) to the mice, they were administered silibinin (50 mg/kg/d, i.p.) or Glehnia littoralis ethyl acetate extract (100 mg/kg/d, oral) therapies once a day for 3 days. After 72 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurement, and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was assessed by a pathologist blinded to the treatment group and divided into 4 categories according to the grade of hepatonecrosis. RESULTS: GLEA significantly improved the beneficial functional parameters in α-amanitin-induced hepatotoxicity. In the histopathological evaluation, the toxicity that was generated with α-amanitin was significantly reduced by GLEA, showing a possible hepatoprotective effect. CONCLUSION: In this murine model, Glehnia littoralis was effective in limiting hepatic injury after α-amanitin poisoning. Increases of aminotransferases and degrees of hepatonecrosis were attenuated by this antidotal therapy.
Agaricales ; Alpha-Amanitin* ; Animals ; Antidotes ; Antioxidants ; Apiaceae* ; In Vitro Techniques ; Liver ; Mice ; Models, Animal ; Mushroom Poisoning ; Oxidative Stress ; Plants ; Poisoning ; Transaminases

PURPOSE: Cardiovascular or respiratory complications of acute intoxication are the most common causes of mortality. Advanced cardiac life support (ACLS) or specific antidotes help manage these cardiac or respiratory complications in acute intoxication. On the other hand, some cases do not respond to ACLS or antidotes and they require some special treatment, such as extracorporeal life support (ECLS). ECLS will provide the chance of recovery from acute intoxication. This study examined the optimal timing of ECLS in acute intoxication cases. METHODS: This paper is a brief report of a case series about ECLS in acute poisoning. The cases of ECLS were reviewed and the effects of ECLS on the blood pressure and serum lactate level of the patients were analyzed. RESULTS: A total of four cases were reviewed; three of them were antihypertensive agent-induced shock, and one was respiratory failure after the inhalation of acid. The time range of ECLS application was 4.8-23.5 hours after toxic exposure. The causes of ECLS implementation were one for recurrent cardiac arrest, two for shock that did not respond to ACLS, and one for respiratory failure that did not respond to mechanical ventilator support. Three patients showed an improvement in blood pressure and serum lactate level and were discharged alive. In case 1, ECLS was stared at 23.5 hours post toxic exposure; the patient died due to refractory shock and multiple organ failure. CONCLUSION: The specific management of ECLS should be considered when a patient with acute intoxication does not recovery from shock or respiratory failure despite ACLS, antidote therapies, or mechanical ventilator support. ECLS improved the hemodynamic and ventilator condition in complicated poisoned patients. The early application of ECLS may improve the tissue perfusion state and outcomes of these patients before the toxic damage becomes irreversible.
Advanced Cardiac Life Support ; Antidotes ; Blood Pressure ; Hand ; Heart Arrest ; Hemodynamics ; Humans ; Inhalation ; Lactic Acid ; Mortality ; Multiple Organ Failure ; Perfusion ; Poisoning* ; Respiratory Insufficiency ; Shock ; Ventilators, Mechanical

PURPOSE: The National Emergency Medical Center has been running a project for the storage and delivery of antidotes for acute poisoning patients of the Department of Health and Welfare, Korea. This study analyzed the results of this project over the past two years. METHODS: The requests received by the National Emergency Medical Center and the data on the delivery process were analyzed. RESULTS: This study analyzed a total of 121 patients with acute poisoning, who were requested to receive an antidote reserved at 20 key hospitals in 2015–2017, and whose age was 52.3±23.5 years; old; 54 were women. Intentional poisoning were 58.7%, and the home was the most common place of exposure (66.9%). The toxic substances were chemicals (32.2%), pesticides (27.3%), medicines (24.8%), and snake venom (4.1%). The patient's poison severity score was 2.4±0.7 (median 3) indicating moderate-to-severe toxicity. Antidote administration was the cases treated in key hospitals 67.8% (82/121), in which transferred patients accounted for 57.3% (47/82). After receiving an antidote request from a hospital other than the key hospitals, the median was 75.5 minutes (range 10 to 242 minutes) until the antidote reached the patient, and an average of 81.5 minutes was required. The results of emergency care were intensive care unit (70.3%), general wards (13.2%), death (10.7%), and discharge from emergency department (5.0%). CONCLUSION: This study showed that the characteristics of acute poisoning patients treated with an antidote were different from previous reports of poisoned patients in the emergency department, and basic data on the time required for delivery from key hospitals was different.
Antidotes* ; Drug Overdose ; Emergencies* ; Emergency Medical Services ; Emergency Service, Hospital* ; Female ; Humans ; Intensive Care Units ; Korea* ; Patients' Rooms ; Pesticides ; Poisoning* ; Running ; Snake Venoms

Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase. The mortality and complication rates of OAC-ICH are high and therefore they are the most feared complication of OAT. Immediate normalization of coagulation is the main goal and therefore knowledge of pharmacodynamics and coagulation status is essential. Laboratory measurements of anticoagulant activity in NOAC patients is challenging as specific tests are not widely available. More accessible tests such as the prothrombin time and activated partial thromboplastin time have important limitations. In dabigatran-associated ICH 5 g Idarucizumab should be administered. In rivaroxaban and apixaban-associated ICHs administration of andexanet alpha should be considered. Prothrombin complex concentrate may be considered if andexanet alpha is not available or in case of an ICH associated with edoxaban.
Anticoagulants* ; Antidotes* ; Avena ; Cerebral Hemorrhage ; Dabigatran ; Hemorrhage* ; Humans ; Mortality ; Partial Thromboplastin Time ; Prothrombin ; Prothrombin Time ; Rivaroxaban ; Vitamin K

Rivaroxaban is a new oral anticoagulant used for the prevention of stroke in patients with atrial fibrillation. Hemorrhagic pericarditis is known to occur with rivaroxaban; however, only a few case reports in the literature describe such events. Recently, we experienced hemorrhagic pericarditis that treated with rivaroxaban for anticoagulation of newly diagnosed, non valvular AF patients with pacemaker. An 83 year old male with permanent pacemaker receiving rivaroxaban 20 mg daily once for 3 months presented at our emergency department complaining of exertional dyspnea. ECG showed intermittent atrial pacing failure and echocardiography showed large amount of pericardial effusion. After urgent pericardiocentesis, which resulted in removal of 500cc bloody fluid, there was an immediate and dramatic improvement in the patient's clinical state. He was discharged without anticoagulation therapy due to concern for further bleeding. This case highlight the potential for bleeding complications associated with novel anticoagulants. Rivaroxaban is being used with increasing frequently in outpatient care. However, no available laboratory test specifically measures the anticoagulant effect of rivaroxaban. Also, in the events of serious bleeding, no specific antidotes, reversal agents were available. Clinicians should be aware of the possibility of hemopericardium in patients treated with anticoagulants, including rivaroxaban who presented with cardiomegaly.
Ambulatory Care ; Anticoagulants ; Antidotes ; Atrial Fibrillation* ; Cardiomegaly ; Dyspnea ; Echocardiography ; Electrocardiography ; Emergency Service, Hospital ; Hemorrhage ; Humans ; Male ; Pericardial Effusion ; Pericardiocentesis ; Pericarditis* ; Rivaroxaban* ; Stroke

Pneumatosis cystoides intestinalis and portomesenteric venous gas are uncommon radiological findings, but are found commonly in cases of bowel ischemia, or as a result of various non-ischemic conditions. A 72-year-old man visited an emergency center with altered mental status 2 hours after ingestion of an unknown pesticide. On physical examination, he showed the characteristic hydrocarbon or garlic-like odor, miotic pupils with no response to light, rhinorrhea, shallow respiration, bronchorrhea, and sweating over his face, chest and abdomen. Laboratory results revealed decreased serum cholinesterase, as well as elevated amylase and lipase level. We made the clinical diagnosis of organophosphate poisoning in this patient based on the clinical features, duration of symptoms and signs, and level of serum cholinesterase. Activated charcoal, fluid, and antidotes were administered after gastric lavage. A computerized tomography scan of the abdomen with intravenous contrast showed acute pancreatitis, poor enhancement of the small bowel, pneumatosis cystoides intestinalis, portomesenteric venous gas and ascites. Emergent laparotomy could not be performed because of his poor physical condition and refusal of treatment by his family. The possible mechanisms were believed to be direct intestinal mucosal damage by pancreatic enzymes and secondary mucosal disruption due to bowel ischemia caused by shock and the use of inotropics. Physicians should be warned about the possibility of pneumatosis cystoides intestinalis and portomesenteric venous gas as a complication of pancreatitis following anticholinesterase poisoning.
Abdomen ; Aged ; Amylases ; Antidotes ; Ascites ; Charcoal ; Cholinesterases ; Diagnosis ; Eating ; Emergencies ; Gastric Lavage ; Humans ; Ischemia ; Laparotomy ; Lipase ; Odors ; Organophosphate Poisoning ; Pancreatitis ; Physical Examination ; Pneumatosis Cystoides Intestinalis ; Poisoning* ; Pupil ; Respiration ; Shock ; Sweat ; Sweating ; Thorax ; Treatment Refusal

Poisoning may result from self-injection. Previous reports have described acute cholinergic crisis, intermediate syndrome, and delayed toxicity resulting from parenteral organophosphate administration. These complications have been managed with antidotal and conservative treatment. Acute kidney injury was not listed among the complications. We report a case of acute kidney injury after intravenous injection with an unknown liquid. After chemical composition analysis, organophosphate dichlorvos has been identified as the injected liquid substance. A 50-year-old man injected this into his left arm. He visited the emergency department with a mental change accompanied by seizure. During admission, there were no typical cholinergic symptoms or intermediate syndrome; however, there was a development of acute oliguric kidney injury. The patient was treated successfully with a combination of hemodialysis, hemoperfusion, and conservative management. The manifested seizure, altered mental state, and acute kidney injury could have been caused by several types of poisoning. Based on patient history, which was obtained during the early treatment period, there was no information of what the injected material may have been, and there were no signs of a typical organophosphate toxidrome. However, the patient was successfully treated with rapid initiation of renal replacement treatment, without the use of antidotes. Poisoning by unknown causative substances poses a diagnostic challenge to emergency physicians. In many cases, treatment may be delayed while the physician tries to identify the toxin. However, the basic toxicology principle of focusing on the patient treatment rather than the poisonous substance should not be forgotten.
Acute Kidney Injury* ; Antidotes ; Arm ; Dichlorvos ; Emergencies ; Emergency Service, Hospital ; Hemoperfusion ; Humans ; Injections, Intravenous* ; Kidney ; Middle Aged ; Organophosphates ; Poisoning ; Renal Dialysis ; Seizures ; Toxicology

Aconitum is a genus of various species of flowering plants that belongs to the Family Ranunculaceae. Most Aconitum sp. have extremely toxic alkaloid substances such as aconitine, mesaconitine and hypaconitine. Among these substances, aconitine can cause fatal cardiotoxicity by activating sodium channels followed by calcium channels in myocardial cells. Even though there have been various therapeutic plans suggested comprising antidotes based on diverse case reports and studies, there is no confirmatory treatment protocol for aconite poisoning. Here, we report an aconite poisoning patient who had refractory ventricular tachyarrhythmia that did not respond to intravenous amiodarone therapies even though they were sustained for over 2 hours, but showed successful recovery following intravenous fat emulsions (IFE) therapy.
Aconitine ; Aconitum* ; Amiodarone ; Antidotes ; Calcium Channels ; Cardiotoxicity ; Clinical Protocols ; Fat Emulsions, Intravenous ; Flowers ; Humans ; Poisoning* ; Ranunculaceae ; Sodium Channels ; Tachycardia

Aconitum is a genus of various species of flowering plants that belongs to the Family Ranunculaceae. Most Aconitum sp. have extremely toxic alkaloid substances such as aconitine, mesaconitine and hypaconitine. Among these substances, aconitine can cause fatal cardiotoxicity by activating sodium channels followed by calcium channels in myocardial cells. Even though there have been various therapeutic plans suggested comprising antidotes based on diverse case reports and studies, there is no confirmatory treatment protocol for aconite poisoning. Here, we report an aconite poisoning patient who had refractory ventricular tachyarrhythmia that did not respond to intravenous amiodarone therapies even though they were sustained for over 2 hours, but showed successful recovery following intravenous fat emulsions (IFE) therapy.
Aconitine ; Aconitum* ; Amiodarone ; Antidotes ; Calcium Channels ; Cardiotoxicity ; Clinical Protocols ; Fat Emulsions, Intravenous ; Flowers ; Humans ; Poisoning* ; Ranunculaceae ; Sodium Channels ; Tachycardia