Toxicological Emergencies Research Articles

The Case Files

The Case Files

Toxicologic Emergencies in the Intensive Care Unit

To review the most common drugs implicated in overdoses admitted to the intensive care unit focusing on antidotes and reversal agents used in their management. Poisonings and overdoses due to pharmaceutical agents result in more than 100 000 critical care unit admissions each year. Ingestion of toxic alcohols, calcium channel blockers, beta-adrenergic antagonists, benzodiazepines, opioids, acetaminophen, tricyclic antidepressants, and salicylates are associated with a high rate of morbidity and mortality. Reviewing the mechanism of toxicity due to specific agents along with the mechanism of action, dosing, and adverse effects of appropriate antidotes is important for the successful management of these patients within the critical care unit. Understanding the most prevalent overdoses and their management using reversal agents and antidotes is essential to the overall treatment of these critically ill patients.

Direct Deposition of Gas Phase Generated Aerosol Gold Nanoparticles into Biological Fluids - Corona Formation and Particle Size Shifts

An ongoing discussion whether traditional toxicological methods are sufficient to evaluate the risks associated with nanoparticle inhalation has led to the emergence of Air-Liquid interface toxicology. As a step in this process, this study explores the evolution of particle characteristics as they move from the airborne state into physiological solution. Airborne gold nanoparticles (AuNP) are generated using an evaporation-condensation technique. Spherical and agglomerate AuNPs are deposited into physiological solutions of increasing biological complexity. The AuNP size is characterized in air as mobility diameter and in liquid as hydrodynamic diameter. AuNP:Protein aggregation in physiological solutions is determined using dynamic light scattering, particle tracking analysis, and UV absorption spectroscopy. AuNPs deposited into homocysteine buffer form large gold-aggregates. Spherical AuNPs deposited in solutions of albumin were trapped at the Air-Liquid interface but was readily suspended in the solutions with a size close to that of the airborne particles, indicating that AuNP:Protein complex formation is promoted. Deposition into serum and lung fluid resulted in larger complexes, reflecting the formation of a more complex protein corona. UV absorption spectroscopy indicated no further aggregation of the AuNPs after deposition in solution. The corona of the deposited AuNPs shows differences compared to AuNPs generated in suspension. Deposition of AuNPs from the aerosol phase into biological fluids offers a method to study the protein corona formed, upon inhalation and deposition in the lungs in a more realistic way compared to particle liquid suspensions. This is important since the protein corona together with key particle properties (e.g. size, shape and surface reactivity) to a large extent may determine the nanoparticle effects and possible translocation to other organs.

The Correlation of Lactate and Carboxyhemoglobin Levels in Carbon Monoxide Poisonings

Carbon monoxide (CO) poisoning is the most common, and perhaps the most serious toxicological emergency in the United States today. Current recommendations suggest that CO levels greater than 25 should be treated with hyperbaric oxygen therapy (HBOT). Lactic acid is produced during periods of tissue hypoxia/ischemia, and has been shown to serve as an independent indicator of disease severity in a number of critical illnesses. The objective of this study is to determine if serum lactate levels on emergency department (ED) presentation have utility as a markers of severity of carbon monoxide poisoning.

Teaching Toxicology With Simulation: A Model Curriculum for Emergency Medicine

Abstract This simulation toxicology curriculum consists of 8-1 hour simulation sessions with effort to teach diagnosis and management of toxicological emergencies to Emergency Medicine Residents in...

The role of chest and abdominal computed tomography in assessing the severity of acute corrosive ingestion

Context. Corrosive substance ingestion is a toxicological emergency with relatively high mortality requiring rational surgical decisions. Objective. Evaluate the role of chest and abdominal computed tomography (CT) in assessing the severity of acute corrosive ingestion. Methods. A retrospective study of adults admitted due to corrosive ingestion, who underwent gastrointestinal endoscopy and CT within 48 h of admission. Endoscopy findings were graded as 0, 1, 2a, 2b, 3a, and 3b (Zargar's criteria), CT findings were graded as 0, 1, 2, and 3. For each patient endoscopy and CT grades were compared, and sensitivity and specificity for predicting mortality or emergency laparotomy were calculated. Results. Twenty-three patients were included, aged 18–87 years; seven underwent emergency laparotomy, five died. Endoscopy grading was higher than CT grading in 14 patients (66%). The sensitivities of endoscopy grades 2b and 3 to predict mortality and emergency laparotomy were 1 and 0.8, respectively; the specificities were 0.38 and 0.37, respectively. The sensitivities of CT grade 3 to predict mortality and emergency laparotomy were 0.4 and 0.28, respectively; the specificities were 0.94 and 0.93, respectively. Three patients had pulmonary infiltrates on CT but not on chest X-ray. Discussion. CT tends to underestimate the severity of corrosive ingestion compared with endoscopy. It has lower sensitivity and higher specificity than endoscopy in predicting major outcome. CT can provide important information on lung injury, and when endoscopy cannot be completed. Conclusion. CT should not be the only basis for surgical decisions during the initial phase of acute corrosive ingestions.

The Feasibility of Evidence- based Decision Making in a Toxicology Emergency Case

Evidence- Based Medicine (EBM) aims to bring the best available evidence into clinical practice. Different clinical methods of education such as in-patient rounds, follow up rounds, out-patients rounds, group sessions, grand rounds, lectures, and journal clubs could be held by EBM approach. The current text presents two interrelated case reports; a case report of EBM decision making in an emergency condition which incorporates a case report of surviving an Aluminum Phosphide poisoned patient by placing Intra Aortic Balloon Pump.

CRISIS: A System for Risk Management

In a situation of an unexpected catastrophe, uncertainty and demand for information are constant. In such a disaster scenario, the CRISIS system arises as a tool to contribute to previous coordination, procedure validation, exercise execution, a good and frequent communication among organizations, and weakness and threat assessment for an appropriate risk management. It offers a wide variety of tools for online communication, consultation and collaboration that, up to this day, includes cartography, tasks, resources, news, forums, instant messaging and chat. As a complement, mathematical models for training and emergency management are being researched and developed. For Argentinean society, it is a necessity to switch from the current handcrafted, bureaucratic emergency management method to a decision-making management model. Previous coordination, exercise execution, a fluid communication among institutions, and threats and weaknesses assessment are required for a proper risk management. With that goal in mind, it is important to reduce confusion, avoid the duplication of efforts to fulfill the same tasks, and have access to a complete vision of the situation, generated from the data of all the organizations taking part. The CRISIS system is a secure web application, accessible to every node in a network formed by the organizations which have complementary responsibilities during prevention and response. It offers a wide variety of tools for online communication, consultation and collaboration that, up to this day, includes cartography, tasks, media (organization and resources), news, forums, instant messaging and chat. As a complement, mathematical models for training and emergency management are being researched and developed. Currently, there are toxicological and epidemiological emergency models available. The present paper analyses, from the perspectives related to risk management for emergencies and disasters, the strengths and weaknesses of the CRISIS system to be used for prevention, response and recoveries in the case of a catastrophe.

Pharmacotherapy of Pediatric Advanced Life Support and Toxicological Emergencies

Guidelines for pediatric advanced life support have been available for nearly a quarter of a century. Recommendations for the pharmacological management of pediatric cardiac arrest have changed over these years. Several important differences have been observed between adult advanced cardiac life support and pediatric advanced life support that must be recognized when children require resuscitation, such as the cause of the arrest, age-specific monitoring parameters, weight-based medication dosing, and obstacles in obtaining venous access. To make matters more complicated, differences also exist across neonatal and pediatric age spectrums. In addition, some toxicological emergencies commonly occurring in children require pharmacological management with agents that have a unique mechanism of action for cardiac support.

Mercury vapor inhalation and poisoning of a family

Acute mercury vapor poisoning is a rare but fatal toxicological emergency. People are exposed to mercury in daily life by the way of foods, vaccines, antiseptics, ointments, amalgam or occupation. We present here, the clinical picture and management of four members of the same family who were exposed to elemental mercury. Three of the family members were seen in another hospital with malaise, fever, eritematous rash and pulmonary problems. Their questioning revealed the mercury exposure. Having a suspicion of heavy metal intoxication, blood and urine mercury levels were measured and mercury intoxication was diagnosed. On admission to our hospital, two patients already had chelation therapy. In three of them we found three distinct abnormalities: encephalopathy, nephrotic syndrome and polyneuropathy. The fourth family member had minor symptoms. This family is an example for the inhalation exposure resulting from inappropriate handling of liquid mercury. During the first days, flu like illness ensues. Then, severe pulmonary, neurological, renal, hepatic, hematological and dermatological dysfunctions develop. Blood and urine mercury levels should be tested on suspicion, but it must be kept in mind that blood level is unreliable in predicting the severity of mercury toxicity. The priority in the treatment should be removing the patient from the source of exposure. Then British anti-Lewisite, edetate calcium disodium, penicillamine, Sodium 2,3-dimercaptopropane-1-sulfhonate and 2,3-dimercaptosuccinic acid can be used for binding the mercury. We conclude that since mercury-containing devices are present in daily life, physicians must be able to recognize the clinical manifestations and treatment of mercury poisoning.

Antidote program in British Columbia

Thanks to Marraffa et al.[1][1] for their interesting article about antidotes for toxicological emergencies. I would like to draw readers’ attention to some of the interesting work being done in British Columbia to assist hospital pharmacists with antidote procurement and use. The British Columbia

Antidotes for toxicological emergencies: A practical review

Appropriate therapies for commonly encountered poisonings, medication overdoses, and other toxicological emergencies are reviewed, with discussion of pharmacists' role in ensuring their ready availability and proper use. Poisoning is the second leading cause of injury-related morbidity and mortality in the United States, with more than 2.4 million toxic exposures reported each year. Recently published national consensus guidelines recommend that hospitals providing emergency care routinely stock 24 antidotes for a wide range of toxicities, including toxic-alcohol poisoning, exposure to cyanide and other industrial agents, and intentional or unintentional overdoses of prescription medications (e.g., calcium-channel blockers, β-blockers, digoxin, isoniazid). Pharmacists can help reduce morbidity and mortality due to poisonings and overdoses by (1) recognizing the signs and symptoms of various types of toxic exposure, (2) guiding emergency room staff on the appropriate use of antidotes and supportive therapies, (3) helping to ensure appropriate monitoring of patients for antidote response and adverse effects, and (4) managing the procurement and stocking of antidotes to ensure their timely availability. Pharmacists can play a key role in reducing poisoning and overdose injuries and deaths by assisting in the early recognition of toxic exposures and guiding emergency personnel on the proper storage, selection, and use of antidotal therapies.

Pharmacotherapy of Pediatric Advanced Life Support and Toxicological Emergencies

Pharmacotherapy of Pediatric Advanced Life Support and Toxicological Emergencies

Pharmacotherapy of Pediatric Advanced Life Support and Toxicological Emergencies

Guidelines for pediatric advanced life support have been available for nearly a quarter of a century. Recommendations for the pharmacological management of pediatric cardiac arrest have changed over these years. Several important differences have been observed between adult advanced cardiac life support and pediatric advanced life support that must be recognized when children require resuscitation, such as the cause of the arrest, age-specific monitoring parameters, weight-based medication dosing, and obstacles in obtaining venous access. To make matters more complicated, differences also exist across neonatal and pediatric age spectrums. In addition, some toxicological emergencies commonly occurring in children require pharmacological management with agents that have a unique mechanism of action for cardiac support.

Nalidixic acid and diabetic ketoacidosis

Sir, Nalidixic acid as the first quinolone was isolated as a by-product of the synthesis of chloroquine. It has been available for the treatment of urinary tract infections for many years.[1] We present here the report of a 13-year-old girl who was referred to the toxicologic emergency department of Baharloo Hospital by a general physician from his office because of seizure and decrease in consciousness. Her seizure was tonic clonic and did not repeat more than one time during hospitalization. There was no history of previous disease. She was diagnosed as diabetic ketoacidosis (DKA) based on her laboratory test results on admission to the hospital, and thus the treatment was started. She was completely cured without any signs and symptoms of diabetes and DKA, 24 h after admission. Her drug history showed nalidixic acid overdosage. Her first complaints were agitation, jerking, and spasm in her upper limbs, along with low consciousness that was diagnosed as seizure by a general physician and cured by administration of diazepam in his office (her seizure might be due to nalidixic acid, but the other etiologic factors such as severe acidosis and electrolyte disturbances might not be ruled out). Her initial vital signs and lab tests on hospital admission are shown in Table 1. Neurological examination was intact except mild agitation and confusion. Fever was not detected. In urine analysis, ketones were large and glucose was 1+. Urine culture was sterile. Arterial blood gas (ABG) was reported as severe acidosis. Chest X-ray was normal. By taking history and performing lab tests, the other etiologies of metabolic acidosis, like renal failure, alcohol drinking, starvation and consumption of other toxins, were ruled out. Table 1 Initial vital signs and lab tests on hospital admission She was diagnosed as DKA and treatment was given with insulin (10 U regular status + 5 U/h), normal saline (2000 mL for 3 h), and potassium (10 mL KCl 15% in 1 L of serum). After continuation of treatment, her blood sugar finally reached 111 mg/dL and ABG became normal [Table 2]. She had a family history of diabetes mellitus as her brother was a diabetic, but there was no history of atopic or epilepsy. Ten empty packets of nalidixic acid (ingested with a suicidal intention) were found near her bed, which was confirmed by history taking after the patient showed clinical improvement. Twenty-four hours after treatment, the patient was completely cured without any symptoms and signs of diabetes and DKA. Table 2 Arterial blood gas and arterial blood glucose data and treatment There are reports of glycosuria[2–4] and hyperglycemia, convulsions, in overdosage of nalidixic acidor even therapeutic dose of nalidixic acid.[5] There are also reports of metabolic acidosis in overdosage[6–9] or therapeutic dose of nalidixic acid.[1,10] To our knowledge, till date there has been no report of DKA following overdosage of nalidixic acid. DKA may be the initial symptom complex that leads to a diagnosis of type 1 DM, but more frequently it occurs in individuals with established diabetes. Nausea and vomiting are often prominent, and their presence in an individual with diabetes warrants laboratory evaluation for DKA[11] Drugs can also be a precipitating factor. There are reports of hyperglycemia, convulsions,[1] and glycosuria in overdosage of nalidixic acid.[2–4] As far as our patient is concerned, she had a positive family history of diabetes mellitus and this presentation may be due to the window period of diabetes mellitus. So, there is a need to follow-up the patient as she could develop overt diabetes mellitus. However, more precautions need to be taken while prescribing nalidixic acid for high-risk patients for diabetes mellitus. As this communication is the first report of its kind, it should encourage aggressive pharmacovigilance in future.

Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies

Context. Lipid infusion is useful in reversing cardiac toxicity of local anesthetics, and recent reports indicate it may be useful in resuscitation from toxicity induced by a variety of other drugs. While the mechanism behind the utility of lipid rescue remains to be fully elucidated, the predominant effect appears to be creation of a “lipid sink”. Objective. Determine whether the extraction of drugs by lipid, and hence the clinical efficacy of lipid rescue in toxicological emergencies can be predicted by specific drug properties. Materials and methods. Each drug investigated was added individually to human drug-free serum. Intralipid® was added to this drug-containing serum, shaken and then incubated at 37°C. The lipid was removed by ultracentrifugation and the concentration of drug remaining in the serum was measured by high-pressure liquid chromatography. Results. In this in vitro model, the ability of lipid emulsion to bind a drug was largely dependent upon the drug's lipid partition constant. Additionally, using a multiple linear regression model, the prediction of binding could be improved by combining the lipid partition constant with the volume of distribution together accounting for approximately 88% of the variation in the decrease in serum drug concentration with the administration of lipid emulsion. Conclusions. The lipid partition constant and volume of distribution can likely be used to predict the efficacy of lipid infusion in reversing the cardiac toxicity induced by anesthetics or other medications.

Goldfrank’s Toxicologic Emergencies

Goldfrank’s Toxicologic Emergencies . By Nelson, L.S., Lewin, N.A., Howland, M.A., Hoffman, R.S., Goldfrank, L.R., Flomenbaum, N.E. . New York : McGraw-Hill Professional , 2010 ; 1968 pp ; 9th ed. ; $259.00 (hardcover ). Goldfrank’s Toxicologic Emergencies is a comprehensive text with relevant and insightful information for any physician in need of assistance in managing the poisoned patient or in need of in-depth analysis of the field. The text has an organized approach with easy-to-navigate contents and colored tables and figures to illustrate the specifics discussed within the text. The text is divided into general sections covering the approach, fundamental principles, and clinical basis of medical toxicology. Each of these general sections is divided into chapters that provide a comprehensive review of the basic principles, utility, and controversies that exist regarding the topic at hand. The first major section covers the general approach to medical toxicology with discussions of principles, diagnostic tests and imaging, decontamination and elimination, pharmacokinetic principles, and resource utilization regarding intensive care unit admissions. Tables, flow charts, and images illustrate these principles throughout this section and act as useful resources for quick review. The next major section discusses fundamental principles, separated into biochemical, molecular, and physiologic bases for toxic exposures. This section helps clarify toxicologic concepts as they relate to both the cellular and organ system levels. It neatly discusses each organ system and its response to toxins, as well as the variety of manifestations seen with different toxins. Again, the colored figures and images supplement the text to better communicate the principles and concepts. This section finishes with discussions of unique populations and their influence on toxicologic processes. From the pediatric to the elderly, from the newborn to the pregnant, this section discusses particular ingestions, exposures, and processes to consider when treating these patients. The next and largest section discusses each class of toxin in depth, paired with its antidotes. The antidote section is particularly useful and, with the color scheme that was absent in the previous edition, these chapters are easy to find and reference. The final section deals with poison centers and epidemiology. This part of the book explores the role of prevention and education, research design, adverse drug events, and postmarketing surveillance. A useful chapter on risk management and legal principles helps complete this text as a comprehensive and thorough discussion of all things related to toxicology. Besides updated information, including new data and references, this book functions better than its predecessor with the addition of colored figures and diagrams that help to more succinctly depict concepts and ideas. The colored contents also aid in easy and quick navigation throughout the text. Overall, Goldfrank’s Toxicologic Emergencies continues to deliver the same high-quality, comprehensive discussion seen in previous editions, with added improvements in readability, flow, images, and figures. Medical toxicology can be complex and overwhelming, but this text helps to deliver the information in an understandable, yet complete format.

Preparedness for the evaluation and management of mass casualty incidents involving anticholinesterase compounds: A survey of emergency department directors in the 12 largest cities in the United States

Anticholinesterases include carbamate and organophosphorus (OP) insecticides and nerve agents. Release of these compounds can flood emergency departments (EDs) with large numbers of poisoned victims and worried individuals. It was hypothesized that despite the focus of disaster preparedness on large metropolitan areas, EDs in these cities would still report self-perceptions of deficiencies in preparedness for mass casualty incidents (MCIs) involving these chemicals. A secure and anonymous online survey was prepared and piloted, and E-mail invitations were sent to the physician directors of the 220 continuously staffed EDs in the 12 most populous incorporated cities in the United States. Forty-six ED directors could not be contacted despite repeated attempts. Of the remaining 174 directors, eight declined and 89 took the survey, for a response rate of 51.1 percent. Fewer than 20 percent were very confident in the effectiveness of their training, and only 4.9 percent were very confident that drills had given them the preparation that they needed. Only 45. 7 percent of reporting hospitals had a board-certified medical toxicologist to help in such an emergency. Almost two-thirds (73.6 percent) of those familiar with the online Radiation Event Medical Management (REMM) module from the National Library of Medicine and the National Institutes of Health thought that a chemical counterpart to REMM would be either moderately or very helpful for MCIs involving anticholinesterases. This study demonstrates that physician ED directors perceived marked deficiencies in their abilities to respond to this kind of toxicological emergency and suggests critical directions for remediation of these deficiencies.

Feline toxicological emergencies: when to suspect and what to do.

Confirmed or suspected intoxications with a wide variety of agents represent a small but important group of feline emergency cases. Generally it is thought that toxicities are less common in cats compared with dogs, with a higher proportion relating to dermal as opposed to oral exposure. Once toxicity is suspected or diagnosed, it must be recognised that treatment regimes may need modification compared with those established for dogs. Different drugs or different dosages may be warranted and the choice of available drugs may be reduced. This review draws on published studies, case reports and clinical experience to summarise key features of the general management of the intoxicated feline patient before describing some of the more serious and common intoxications in more detail. The focus throughout the review is on the peculiarities of feline metabolism and how they may impact on presentation and treatment. The aim is to assist companion animal and feline practitioners, who are in the frontline when it comes to managing these emergency cases.

Toxicological Emergencies and Their Management at Different Health Care Levels in Northern India-An Overview*

Toxicological Emergencies and Their Management at Different Health Care Levels in Northern India-An Overview*