Specific Antidotal Therapy Research Articles

The use of CytoSorb in acute oral mercuric chloride poisoning at a potentially lethal dose.

The study aims to present a case of acute mercuric chloride poisoning treated successfully with continuous renal replacement therapy using the CytoSorb filter. A 21-year-old female patient after a suicide attempt by intentional ingestion of mercuric chloride, was admitted to the hospital with features of multiple organ damage for specific treatment. The performed laboratory tests confirmed high levels of mercury in the blood (1051 μg/L) and urine (22,960 μg/L). Due to acute renal failure, continuous renal replacement therapy (CRRT) CVVHD Ci-Ca was initiated; the procedure was then converted to CVVHDF Ci-Ca with ultrafiltration to optimise therapy, and CytoSorb was added to the artificial kidney system on day 3. Specific antidote therapy (DMPS) was administered concurrently. The ongoing treatment resulted in a reduction in subjective complaints, a decrease in blood mercury levels to 580 μg/L, and an improvement in parenchymal organ function. In the event of poisoning with inorganic mercury compounds (mercuric chloride), continuous renal replacement therapy using the CytoSorb filter as an extracorporeal blood purification method may be considered.

Modern possibilities and prospects in evaluating the anticoagulant effect of direct oral anticoagulants

Currently, direct oral anticoagulants (DOACs) should be preferred when prescribing anticoagulant therapy to atrial fibrillation patients because of their lower potential for interactions and risk of bleeding than warfarin. However, in the absence of standardized laboratory tests and a specific antidote (except dabigatran), prescribing and monitoring DOAC therapy remains a challenge for clinicians and patients. The present review focuses on the problems of DOAC laboratory evaluation, indications, and prospects for its use. Routine coagulation tests including activated partial thromboplastin time, prothrombin time and thrombin time are not recommended for DOAC therapy. Currently, there are specific coagulation tests (anti-Xa activity factor determination for apixaban/ rivaroxaban and diluted thrombin time for dabigatran) that allow judging the presence of the drug in the blood. According to current recommendations, these tests should be used only to assess anticoagulant concentrations and not to adjust doses and decide on the timing of withdrawal before invasive intervention. Nevertheless, the issue of determining DOAC concentration during invasive interventions, the need for which only increases with age, is most relevant. Also a possible additional factor that may alter the bioavailability and pharmacokinetics of DOAC and be taken into account in the evaluation of laboratory activity is the presence of chronic renal disease, hepatic insufficiency, low or excess body weight. The use of specific coagulation tests for patients undergoing elective and urgent surgery among special categories of patients (with chronic kidney disease, low or excess body weight, renal failure) is promising.

Management of bleeding in patients on antithrombotic therapy

Severe bleeding under antithrombotic therapy is common and challenging in intensive care medicine; on the one hand, rapid bleeding control must be achieved and, on the other hand, thromboembolic complications must be avoided. The paper will provide abrief overview of direct oral anticoagulants, therapeutic options and precise instructions for dealing with severe bleeding. In addition to general measures in direct oral anticoagulant (DOAC)-associated major bleeding, prothrombin complex concentrate (PCC), idarucizumab and andexanet alfa are available as specific antidote therapy. In case of bleeding under heparin therapy, protamine sulfate is available as apossible antidote. In particular, the importance of andexanet alfa in the treatment of factor Xa inhibitor-associated bleeding requires further investigation.

Specific antidote therapy in dogs: modern aspects

Current laws of the Russian Federation provide for responsible treatment of animals. Nevertheless, there is an acute problem of the growing number of uncared for dogs. The article addresses issues of dog protection focused on the prevention of dog poisoning by medications illegally used by dog hunters, as well as on dog training aspects and methods of specific antidote therapy. Cytoprotective activity of ubiquinone is studied in view of biochemical profile in dogs.

Favorable Outcome of Severe Poisoning by Snake Green Mamba (<i>Dendroaspis viridis</i>) Clinical Case

This clinical case of acute poisoning due to bite of snake Dendroaspis viridis seems interesting to share because of its rare incidence inRussiaand management peculiarities: the critical care was conducted without specific antidote therapy due to absence of the antidote.The prevailing clinical presentation included signs of toxic myopathy combined with paresis of skeletal and breathing muscles that led to development of acute respiratory failure and metabolic disorders. The processes described were induced by the action of snake poison dendrotoxins featuring the activities of potassium channel blockers and acetyl cholinesterase inhibitors.The proper critical care included conduct of syndrome therapy aimed at maintaining life support systems adequately to condition (replacement of the breathing and circulation functions), antibiotic therapy and desensitizing treatment and metabolic care by administration of drugs characterized by antihypoxant/antioxidant mechanism of action.The comprehensive therapy applied has resulted in a favorable outcome of acute poisoning by snake green mamba without development of possible complications even when the specific antidote drug has not been included into the treatment protocol.

The Toxicology Investigators Consortium Case Registry-the 2017 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. The objective of this eighth annual report is to summarize the Registry's 2017 data and activity with its additional 7577 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2017. Detailed data was collected from these cases and aggregated to provide information which includes demographics (e.g., age, gender, race, ethnicity), reason for medical toxicology evaluation (e.g., intentional pharmaceutical exposure, envenomation, withdrawal from a substance), agent and agent class, clinical signs and symptoms (e.g., vital sign abnormalities, organ system dysfunction), treatments and antidotes administered, fatality, and life support withdrawal data. Females were involved in 50.4% of cases. Transgender demographic information collection was initiated in 2017 to better represent the population and there were 36 cases involving transgender patients. Adults aged 19-65 were the most commonly reported age group. Non-opioid analgesics were the most commonly reported agent class, with acetaminophen again the most common agent reported. There were 93 fatalities reported in 2017. Treatment interventions were frequently reported with 30.6% receiving specific antidotal therapy. Major trends in demographics and exposure characteristics remained similar to past years' reports. While treatment interventions were commonly required, fatalities were rare.

Successful management of bupropion poisoning: possible benefit of acidosis treatment

Bupropion is used as an antidepressant and smoking cessation aid. It has been described in the literature as a norepinephrine - dopamine reuptake inhibitor and is also a nicotinic antagonist. Bupropion itself is not a common cause of intoxication cases seen in Emergency Department (ED). The most important side effect is an increase in risk for epileptic seizures. We aimed to present the management of a 29-year-old female patient in ED with epileptic seizures and acidosis due to bupropion intoxication,who had taken 30 bupropion 150 mg tablets and 16 fluoksetin 20 mg tablets for suicidal purpose. According to her blood gas counts sodium bicarbonate therapy was begun in ED and after having response to the treatment was continued in intensive care unit. She was discharged three days later without any other seizures and complications. Although bupropion intoxication is rare it can cause severe metabolic acidosis and epileptic seizures. There is no specific antidote therapy to bupropion so symptomatic therapy still have benefit.

The Toxicology Investigators Consortium Case Registry-the 2015 Experience.

The American College of Medical Toxicology established the Toxicology Investigators Consortium (ToxIC) Case Registry in 2010. The Registry contains all medical toxicology consultations performed at participating sites. The Registry has continued to grow since its inception, and as of December 31, 2015, contains 43,099 cases. This is the sixth annual report of the ToxIC Registry, summarizing the additional 8115 cases entered in 2015. Cases were identified by a query of the Registry for all cases entered between January 1 and December 31, 2015. Specific data reviewed for analysis included demographics (age, race, gender), source of consultation, reason for consultation, agents and agent classes involved in exposures, signs, symptoms, clinical findings, fatalities, and treatment. By the end of 2015, there were 50 active sites, consisting of 101 separate health-care facilities; 51.2% of cases involved females. Adults between the ages of 19 and 65 made up the majority (64.2%) of Registry cases. Caucasian race was the most commonly reported (55.6%); 9.6% of cases were identified as Hispanic ethnicity. Inpatient and emergency department referrals were by far the most common referral sources (92.9%). Intentional pharmaceutical exposures remained the most frequent reason for consultation, making up 52.3% of cases. Of these intentional pharmaceutical exposures, 69% represented an attempt at self-harm, and 85.6% of these were a suicide attempt. Nonopioid analgesics, sedative-hypnotics, and antidepressant agents were the most commonly reported agent classes in 2015. Almost one-third of Registry cases involved a diagnosed toxidrome (32.8%), with a sedative-hypnotic toxidrome being the most frequently described. Significant vital sign abnormalities were recorded in 25.3% of cases. There were 98 fatalities reported in the Registry (1.2%). Adverse drug reactions were reported in 4.3 % of cases. Toxicological treatment was given in 65.3% of cases, with 33.0% receiving specific antidotal therapy. Exposure characteristics and trends overall were similar to prior years. While treatment interventions were required in the majority of cases, fatalities were rare.

Emergency management of intoxications in the dog and cat

Intoxications may lead to life-threatening emergencies. While stabilising the patient, therapy should focus on a rapid and effective elimination of the toxin. General measures for decontamination (gastrointestinal, dermal, ocular) aim to effectively decrease the absorption of the poisonous substance. Further classification of the substance and its properties can assist with the choice of specific treatment options, including dialysis and specific antidotal therapy. In recent years, treatment with lipid emulsions for enhanced elimination of lipophilic substances has become an important therapeutic option. In affected patients, it can rapidly improve clinical signs while side effects and complications are rarely encountered with this form of therapy.

Patterns of Acute Poisoning in Childhood in Zagazig, Egypt: An Epidemiological Study.

Background. Acute poisoning represents one of the most common medical emergencies in childhood. In view of paucity of literature on accidental poisoning among children in Egypt, this study was designed to describe the pattern of childhood poisoning in Zagazig University Hospitals. Patients and Methods. This retrospective study included 300 children up to 12 years with acute poisoning admitted to the Pediatric Department and Poisoning Treatment Unit, Zagazig University Hospitals, from January 2011 to August 2012. Complete epidemiological and clinical data were recorded and analyzed. Results. Three hundred of poisoned children were enrolled in this study. Children from 1 to 6 years were more liable to poisoning (81%). More boys than girls were poisoned at all age groups. The majority of all cases (99%) were due to accidental poisoning. Overall, 32% of the poisoned cases were living in Zagazig city while 68% were living in the rural areas. The presenting symptoms were classic in 60% of the cases. Pesticides, therapeutic drugs, and cleaning and disinfectant agents were the most frequent poisoning agents (28.7%, 22.7%, and 17.0%, resp.). In 86.0% of cases, observation with or without supportive measures together with decontamination and specific antidote therapy whenever needed was sufficient. Conclusion. Most of the poisonings were due to accidental ingestions by infants and young children. Pesticides and medications were the most commonly involved agents.

Intrathecal Methotrexate-Induced Posterior Reversible Encephalopathy Syndrome (PRES).

Posterior reversible encephalopathy syndrome (PRES) is an acute neuroradiological diagnosis presenting with headache, vomiting, seizure, abnormalities of the mental status, and visual disturbances associated with a breakdown in cerebral vasculature regulation. It has a unique neuroradiological pattern of symmetrical parietooccipital vasogenic edema [1]. The most common causes of this syndrome are sudden arterial hypertension, preeclampsia, eclampsia, uremia, immunosuppressive drugs, and cancer chemotherapies such as cyclosporine, tacrolimus, L-asparaginase, vincristine, gemcitabine, cytarabine, and cisplatin, typically used in cases of hematopoietic malignancies [2,3,4,5,6,7]. Intrathecal methotrexate-induced PRES in an adult is exceedingly rare [8]. A 43-year-old woman was admitted to gynecology with metrorrhagia. Cervical cancer was diagnosed and radical hysterectomy with lymph node dissection was performed. Final pathology and immunohistochemical analyses revealed B-cell phenotype malign lymphoma, which is consistent with Burkitt lymphoma. A chemotherapy treatment protocol with R-Hyper CVAD, consisting of rituximab, cyclophosphamide, vincristine, adriamycin, and dexamethasone plus 12 mg of intrathecal methotrexate without preservative, was then started. Twelve days after chemotherapy she had severe analgesic-irresponsive headache, nausea, motor agitation, and cooperation failure. Her vital signs and laboratory findings were normal. Cranial computed tomography revealed hypodense areas due to edema in the bilateral cerebral hemispheres, predominantly in the posterior regions. Magnetic resonance imaging (MRI) of the brain showed multiple confluent hyperintense lesions in T2-weighted and fluid-attenuated inverse recovery (FLAIR) sequences (Figure 1a), with no contrast enhancement in T1-weighted sequences. PRES was diagnosed and she was admitted to the intensive care unit (ICU) because of decreased alertness and agitation. Intrathecal methotrexate treatment was discontinued. On the second day in the ICU her blood pressure rose and was then normalized by diltiazem infusion. On the third day in the ICU, myoclonic jerks were seen in all extremities. Levetiracetam was started. Myoclonic symptoms were no longer observed. After treatment she had no neurological symptoms. Three weeks later, cranial MRI showed significantly improved brain lesions (Figure 1b). The 6-month follow-up was uneventful. Informed consent was obtained. Figure 1a MRI FLAIR images show bilateral multiple subcortical and cortical hyperintense lesions. Figure 1b MRI images 3 weeks after developing PRES revealed significant improvement. During chemotherapy for hematopoietic malignancies, possible causes of neurological symptoms (cerebrovascular disease, metabolic disturbances, neoplasia, and infections) must be excluded by clinical, biological, and imaging findings. During chemotherapy, various types of anticancer drugs are administered, and it is difficult to identify which drug induces PRES. In our case, intrathecal methotrexate treatment was stopped, and the patient’s symptoms were relieved and did not reoccur while her treatment was continued with other anticancer drugs. In treatment, the causal factor must be discontinued. The treatment of overdose of intrathecal methotrexate is dilution and removal from the cerebrospinal fluid with specific antidotal therapy. Leucovorin and anti-inflammatory agents are useful [9]. Although PRES is usually reversible with patient recovery and resolution of the imaging findings, it might be recurrent or result in permanent damage [10,11].

A rare case of multiple rattlesnake bites

The rattlesnake (Crotalus adamanteus) is a venomous viper inhabiting the southeastern parts of the United States. It is not found in the Balkans and Europe habitats. Subjects of the species are grown and seen in museums, exhibitions and terrariums, and sometimes in private collections. This may generate potentially toxic exposures to the venom in accidental contact. Acute poisoning with rattlesnake poison in Bulgaria is exotic, rare and even casuistic. The venom of the rattlesnake exhibits neuropathic, proteolytic and hemolytic activities. Antivenom is not currently easily available in Bulgaria--it is not usually stored in hospitals because it is very rarely used and therefore rather expensive. We present a case of multiple envenomation (two different occasions) of one and the same person who kept rattlesnakes in a private terrarium. Local toxic syndrome was observed with burning and stinging pain at bite site combined with limited hemorrhage and necrosis. The hemolytic reaction and the local toxic results were successfully managed without resorting to any specific antidotal therapy.

Successful treatment of polymedicamentous poisoning with metoprolol, diltiazem and cilazapril

Poisoning caused by drugs with cardiodepressive effects is an urgent condition in medicine which is associated with high mortality rate regardless of modern therapeutic methods. Accidental or intentional poisoning whit these drugs produces heart activity depression and cardiovascular collapse as consequences. Current therapy for severe poisoning caused by beta-blockers and calcium channel blockers includes both unspecific and specific antidote therapy whit glucagon, as well as application of adrenergic drugs, calcium, phosphodiesterase inhibitors and hyperinsulinemia/euglycemia therapy. However, even whit the application of these drugs, prompt measures of unspecific detoxication therapy and cardiopulmonary reanimation are crucial for survival of patients with severe poisoning. A 28-year-old female patient was hospitalized for cardiogenic shock and altered state of conscioussnes (Glasgow coma score = 4), caused by acute poisoning with 2 g of metoprolol (Presolol), 1.8 g of diltiazem (Cortiazem) and 50 mg of cilazapril (Zobox). Prolonged cardiopulmonary resuscitation was applied during the first 16 hours of hospitalization, including administration of crystaline solutions (8 L), 17 mg of adrenaline, 4 mg of atropine, 4 mg of glucagone and 1.6 g of dopamine, with electro-stimulation by temporary pacemaker and mechanical ventilation. In a defined time period, normalized state of consciousness was registered, mechanical ventilation was stopped and normal heart activity and hemodynamic stability were accomplished. During hospitalization the patient was treated for mild pneumonia and after ten days, completely recovered, was released and sent to home treatment. Prompt measures of cardiopulmonary resuscitation and multidisciplinary treatment in intensive care units significantly increase the chances of complete recovery of a patient with severe poisoning caused by drugs with cardiodepressive efects.

Adjuncts and Alternatives to Oxime Therapy in Organophosphate Poisoning—is There Evidence of Benefit in Human Poisoning? A Review

Organophosphate poisoning is common in developing countries. The morbidity and mortality with organophosphate poisoning is relatively high despite the use of atropine as specific antidotal therapy and oximes to reactivate acetylcholinesterase. Several adjunct and alternative therapies have been explored in animal and human studies. We reviewed the literature to ascertain if there was evidence of benefit of such therapies. Adjunct and alternative therapies included treatments to reduce poison absorption by topical application of creams, enhance toxin elimination by haemoperfusion or bioremediation and neutralise the poison by scavenging free organophosphate with cholinesterase-rich human plasma. In addition, magnesium, clonidine, diazepam, N-acetyl cysteine and adenosine receptor agonists have also been used to counteract poison effects. Detailed assessment was limited by the paucity of trials on adjunct/alternative therapies. The limited evidence from the review process suggested potential benefit from the use of human plasma infusion, early initiation of haemoperfusion and intravenous magnesium, in addition to standard therapy with atropine and pralidoxime. There appeared to be no additional benefit with alkalinisation or use of glycopyrrolate instead of atropine in human trials. Diazepam administration has been advocated by military authorities if symptoms developed following exposure to organophosphate. Bioremediation, clonidine, N-acetyl cysteine and adenosine receptor agonists have been evaluated only in animal models. The impact of adjunct and alternate therapies on outcomes in human poisoning needs to be further explored before implementation as standard treatment.

Intrathecal methotrexate neurotoxicity: clinical correlates and antidotal treatment

The neurotoxicity of methotrexate (MTX) is more severe when administered intrathecally (IT) than by the oral and intravenous (IV) routes, and has been reported even with a single administration of therapeutic doses of 12 or 15 mg. Prompt recognition and treatment are essential to improve the outcome after massive IT-MTX overdose. Treatment options include CSF drainage or CSF exchange, ventriculolumbar perfusion, IT corticosteroids to reduce CSF inflammation and IV leucovorin to reduce systemic toxicity. Toxicity resulting from IT injection of leucovorin is controversial. CSF drainage and exchange are particularly effective if performed soon after the overdose. In this paper we describe a protocol of treatment for severe cases of IT-MTX overdose in excess of 100 mg. The mainstay of treatment is dilution and removal from CSF of excessive methotrexate alongside with specific antidotal therapy.

Newer antidotal therapies for pediatric poisonings

Specific antidotal therapy is essential for the successful management of a limited number of intoxications. Newer antidotes have emerged in the last 10 years that target specific life-threatening poisonings. These newer therapies, including hormones, drug antagonists, enzyme inhibitors, and antibodies against drugs and venoms, illustrate the spectrum of mechanisms by which an antidote can reverse toxicity of a poison. This report focuses on seven newer antidotes: glucagon (β-blocker and calcium channel blocker toxicity), insulin/glucose (calcium-channel blocker toxicity), octreotide (sulfonylurea toxicity), new crotalid antivenom (crotalid snake bit envenomation), antibody therapy for tricyclic antidepressants, fomepizole (ethylene glycol toxicity), and nalmefene (opiod toxicity). The antidotes' mechanisms of action, expected therapeutic actions, indications for use, adverse effects, dosing, and limitations are discussed.

Acute Ocular Effects of Mustard Gas: Anatomic Pathology and Immunohistopathology of Exposed Cornea

Sulfur mustard gas (HD), a synthetic vesicating agent used effectively as a major chemical warfare agent during World War 1, continues to be a modern day threat agent. Unfortunately there is no specific pretreatment or antidotal therapy for those who may become exposed. Whole body exposure results in cutaneous, respiratory and ocular effects. of these, eye impairment leads to the most immediate incapacitation. However HD-induced eye lesions remain to be fully characterized. In the present study we explore histological, ultrastructural and immunopathological effects of a vesicating dose of HD in rabbit cornea occurring during the first 24 hours following exposure.A 0.4μl drop of liquid HD was placed on the left cornea of anesthetized rabbits. The right cornea served as an unexposed control. Following exposure animals were returned to their cages and given appropriate care by an attending veterinarian. Eye injury was evaluated by clinical observations and given scores of severity from simple conjunctival redness to apparent corneal damage.

The Poisoned Child: Evolving Concepts in Care

More than 1 million children in the United States ingest poisons each year. The vast majority of these exposures result in no harm to the child. The task of the emergency physician is to discern which children are at risk and treat those children with appropriately aggressive therapy while minimizing intervention for the rest. In pediatric exposure cases, the toxin is usually identified. A careful toxic differential diagnosis will lead to a list of likely poisons in symptomatic patients without an identified exposure. The cornerstone of treatment remains the evaluation of the ingestion episode, careful assessment of the patient, and the application of basic supportive medical care. In the ED, when it has been determined that gastrointestinal decontamination is indicated on the basis of the substance and quantity ingested, activated charcoal is the decontamination agent of choice if the substance ingested is absorbed by activated charcoal. Gastric emptying should be restricted to those circumstances when the substance ingested is not bound to activated charcoal or the rare event when a child presents to the ED within 1 hour of ingestion with significant CNS depression. Whole bowel irrigation is a recently described technique to enhance the passage of drugs already beyond the pylorus. The indications for its use are poorly defined. Laboratory tests are generally overordered after pediatric ingestions. Appropriate use of the laboratory includes an assessment of basic serum chemistry studies in symptomatic patients, confirmation of suspected toxins, and the determination of the need for specific antidotal therapy. General "drug screens" are expensive and rarely contribute to patient care. Use of specific therapies, including antidotes and enhanced elimination techniques, should be limited to those cases when expectation that a defined benefit outweighs the risk of the procedure is reasonable. The indications for the use of these interventions in children may be different from those for adults.

Use of Hemoperfusion in Experimental Intoxication with Nerve Agents

The aim of this study was to evaluate the efficiency of hemoperfusion (HP) through coated resin adsorbent Synachrom E-5 in animal intoxications with organophosphate inhibitors of cholinesterases type of nerve agents. Five anesthetized dogs were intoxicated with 2 to 6 LD50 of VX substance and another 4 with 2 to 3 LD50 sarine. Both nerve agents were given i.m. after starting 5 h HP. The clinical and laboratory tests were monitored during each HP. HP therapy prevented the development of serious signs of intoxication provided that the administered quantity of both sarine and the VX substance was only 2 doses of LD50. Specific antidote therapy was necessary to prevent cardiorespiratory failure in animals intoxicated with a higher dose of poison. The results obtained show that HP through Synachrom E-5 in intoxication with nerve agents sarine and the VX type is only partially successful.

Cyanide overdose: Survival with fatal blood concentration without antidotal therapy

Cyanide poisoning is an uncommon emergency department problem. It has a high mortality, and specific antidotal therapy can be lifesaving. We describe a 23-year-old man who ingested potassium cyanide and survived without antidotal therapy. His blood cyanide concentration was 4.65 mg/L, which is within the lethal range. The arterial venous oxygen saturation gradient was considered in the decision regarding antidote administration. Our experience underscores the importance of supportive care.