2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Patients with Altered Mental Status May Benefit from Medical Toxicology Consultation.

BACKGROUND: Presentation of intoxicated patients to hospitals is frequent, varied, and increasing. Medical toxicology expertise could lead to important changes in diagnosis and treatment, especially in patients presenting with altered mental status. OBJECTIVES: To describe and analyze clinical scenarios during a 1-year period after the establishment of a medical toxicology consultation service (MTCS). METHODS: Cases of 10 patients with altered mental status at presentation were evaluated. Medical toxicology consultation suggested major and significant changes in diagnosis and management. RESULTS: Of 973 toxicology consultations performed during the study period, bedside consultation was provided for 413 (42%) patients. Of these 413, 88 (21%) presented with some level of altered mental status. We described 10 patients in whom medical toxicology consultation brought about major and significant changes in diagnosis and management. CONCLUSIONS: Benefits may be derived from medical toxicology consultations, especially in patients with altered mental status. Medical toxicology specialists are well positioned to provide high value and expedited patient care.

Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity.

BACKGROUND: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs). OBJECTIVES: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population. METHODS: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death). RESULTS: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death. CONCLUSION AND RELEVANCE: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.

Using a decision tree algorithm to distinguish between repeated supra-therapeutic and acute acetaminophen exposures.

BACKGROUND: This study aimed to compare clinical and laboratory characteristics of supra-therapeutic (RSTI) and acute acetaminophen exposures using a predictive decision tree (DT) algorithm. METHODS: We conducted a retrospective cohort study using the National Poison Data System (NPDS). All patients with RSTI acetaminophen exposure (n = 4,522) between January 2012 and December 2017 were included. Additionally, 4,522 randomly selected acute acetaminophen ingestion cases were included. After that, the DT machine learning algorithm was applied to differentiate acute acetaminophen exposure from supratherapeutic exposures. RESULTS: The DT model had accuracy, precision, recall, and F1-scores of 0.75, respectively. Age was the most relevant variable in predicting the type of acetaminophen exposure, whether RSTI or acute. Serum aminotransferase concentrations, abdominal pain, drowsiness/lethargy, and nausea/vomiting were the other most important factors distinguishing between RST and acute acetaminophen exposure. CONCLUSION: DT models can potentially aid in distinguishing between acute and RSTI of acetaminophen. Further validation is needed to assess the clinical utility of this model.

Comparison of decision tree with common machine learning models for prediction of biguanide and sulfonylurea poisoning in the United States: an analysis of the National Poison Data System.

BACKGROUND: Biguanides and sulfonylurea are two classes of anti-diabetic medications that have commonly been prescribed all around the world. Diagnosis of biguanide and sulfonylurea exposures is based on history taking and physical examination; thus, physicians might misdiagnose these two different clinical settings. We aimed to conduct a study to develop a model based on decision tree analysis to help physicians better diagnose these poisoning cases. METHODS: The National Poison Data System was used for this six-year retrospective cohort study.The decision tree model, common machine learning models multi layers perceptron, stochastic gradient descent (SGD), Adaboosting classiefier, linear support vector machine and ensembling methods including bagging, voting and stacking methods were used. The confusion matrix, precision, recall, specificity, f1-score, and accuracy were reported to evaluate the model's performance. RESULTS: Of 6183 participants, 3336 patients (54.0%) were identified as biguanides exposures, and the remaining were those with sulfonylureas exposures. The decision tree model showed that the most important clinical findings defining biguanide and sulfonylurea exposures were hypoglycemia, abdominal pain, acidosis, diaphoresis, tremor, vomiting, diarrhea, age, and reasons for exposure. The specificity, precision, recall, f1-score, and accuracy of all models were greater than 86%, 89%, 88%, and 88%, respectively. The lowest values belong to SGD model. The decision tree model has a sensitivity (recall) of 93.3%, specificity of 92.8%, precision of 93.4%, f1_score of 93.3%, and accuracy of 93.3%. CONCLUSION: Our results indicated that machine learning methods including decision tree and ensembling methods provide a precise prediction model to diagnose biguanides and sulfonylureas exposure.

Outcome prediction of methadone poisoning in the United States: implications of machine learning in the National Poison Data System (NPDS).

Methadone is an opioid receptor agonist with a high potential for abuse. The current study aimed to compare different machine learning models to predict the outcomes following methadone poisoning. This six-year retrospective longitudinal study utilizes National Poison Data System (NPDS) data. The severity of outcomes was derived from the NPDS Coding Manual. Our database was divided into training (70%) and test (30%) sets. We used a light gradient boosting machine (LGBM), extreme gradient boosting (XGBoost), random forest (RF), and logistic regression (LR) to predict the outcomes of methadone poisoning. A total of 3847 patients with methadone exposures were included. Our results demonstrated that machine learning models conferred high accuracy and reliability in determining the outcomes of methadone poisoning cases. The performance evaluation showed all models had high accuracy, precision, specificity, recall, and F1-score values. All models could reach high specificity (more than 96%) and high precision (80% or more) for predicting major outcomes. The models could also achieve a high sensitivity to predict minor outcomes. Finally, the accuracy of all models was about 75%. However, XGBoost and LGBM models achieved the best performance among all models. This study showcased the accuracy and reliability of machine learning models in the outcome prediction of methadone poisoning.

Decision tree algorithm can determine the outcome of repeated supratherapeutic ingestion (RSTI) exposure to acetaminophen: review of 4500 national poison data system cases.

This study is aimed at establishing the outcome of RSTI exposure to acetaminophen based on a decision tree algorithm for the first time. This study used the National Poison Data System (NPDS) to conduct a six-year retrospective cohort analysis, which included 4522 individuals. The patients had a mean age of 26.75 ± 16.3 years (1-89). 3160 patients (70%) were females. Most patients had intentional exposure to acetaminophen. Almost all the patients had acetaminophen exposure via ingestion. In addition, 400 (8.8%) experienced major outcomes, 1500 (33.2%) experienced moderate outcomes, and 2622 (58%) of the patients experienced mild ones. The decision tree model performed well in the training and test groups. In the test group, the accuracy was 0.813, precision of 0.827, recall being 0.798, specificity 0.898, and an F1 score 0.80. In the training group, accuracy was 0.831, recall was 0.825, precision was 0.837, specificity was 0.90, and F1 score was 0.829. Our results showed that serum liver enzymes being present at elevated levels (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) greater than 1000 U/L followed by ALT, AST between 100 and 1000 U/L), prothrombin time (PT) prolongation, bilirubin increase, renal failure, confusion, age, hypotension, other coagulopathy (such as partial thromboplastin time (PTT) prolongation), acidosis, and electrolyte abnormality were the effective factors in determining the outcomes in these patients. The decision tree algorithm is a dependable method for establishing the prognosis of patients who have been exposed to RSTI acetaminophen and can be used throughout the patients' hospitalization period.

A Case Report of Venezuelan Suntiger Tarantula (Psalmopoeus Irminia) Envenomation and Review of Tarantula Exposures.

BACKGROUND: Tarantula envenomations are encountered infrequently but may increase with increased exotic animal ownership. This case report presents the first documented toxicity from a Venezuelan suntiger tarantula (VST), Psalmopoeus irminia, and provides a general framework for approaching patients with tarantula exposures. CASE REPORT: A 35-year-old man presented to an emergency department 4 h after experiencing a bite from his pet VST. He developed erythema, pain, and edema to the bite site on the left thenar eminence that extended proximally. Within 4 h, he developed abdominal pain, nausea, vomiting, throat itching, and tightness. The patient had a blood pressure of 131/105 mm Hg, heart rate of 102 beats/min, 36.6°C, respiratory rate of 20 breaths/min, and SpO2 of 94%. Laboratory evaluations were within normal limits (other than chronically elevated but improved transaminases). The patient received 0.5 mg epinephrine intramuscularly, 50 mg diphenhydramine IV, 20 mg famotidine IV, 0.4 mg ondansetron IV, and 1 L of normal saline for a suspected anaphylactic reaction. Shortly after epinephrine administration, his gastrointestinal and upper airway symptoms resolved. All symptoms resolved within 1 week. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Little is known about VST toxicity. Therefore, providers should rely on a general framework for approaching patients with tarantula exposures. Morbidity from tarantula exposures is mediated by mechanical injury, venom effects, and hypersensitivity reactions. Typical clinical findings include local pain, pruritis, edema, erythema, and burning. Muscle cramping, ophthalmia nodosa, and hypersensitivity reactions may occur. Treatment is primarily supportive and includes decontamination, cool compresses, analgesia, treatment of anaphylaxis, and ophthalmology evaluation if ocular exposure.

Distinguishing characteristics of exposure to biguanide and sulfonylurea anti-diabetic medications in the United States.

OBJECTIVES: Biguanides and sulfonylureas are anti-hyperglycemic drugs commonly used in the United States. Poisoning with these drugs may lead to serious consequences. The diagnosis of biguanide and sulfonylurea poisoning is based on history, clinical manifestations, and laboratory studies. METHODS: This study is a six-year retrospective cohort analysis based on the National Poison Data System. Clinical effects of 6183 biguanide and sulfonylurea exposures were identified using binary logistic regression. RESULTS: The mean age of patients with biguanide and sulfonylurea exposure was 39.27 ± 28.91 and 28.91 ± 30.41 years, respectively. Sulfonylurea exposure is most commonly seen via unintentional exposure, while biguanide exposure frequently occurs as a result of intentional ingestion. Minor and moderate outcomes commonly developed following biguanide and sulfonylurea exposure, respectively. Sulfonylurea exposure was less likely to develop clinical effects abdominal pain, metabolic acidosis, diarrhea, nausea, vomiting, and elevated creatinine than patients ingesting biguanides. However, sulfonylurea exposure was more likely to cause dizziness or vertigo, tremor, drowsiness or lethargy, agitation, diaphoresis, and hypoglycemia. CONCLUSIONS: Our study is the first to use a wide range of national data to describe the clinical characteristics that differentiate the toxicologic exposure to biguanides and sulfonylureas. Sulfonylurea exposure is commonly seen via unintentional exposure, while metformin exposure is frequently seen via intentional exposure. Sulfonylurea toxicity is more likely to cause agitation, dizziness or vertigo, tremor, diaphoresis, and hypoglycemia, while metformin exposure induces abdominal pain, acidosis, diarrhea, nausea, vomiting, and elevated creatinine.

Levocarnitine for the Treatment of Valproic Acid-Induced Hyperammonemic Encephalopathy in Children: The Experience of a Large, Tertiary Care Pediatric Hospital and a Poison Center.

BACKGROUND: Although rare, symptomatic hyperammonemia is sometimes associated with valproic acid (VPA), especially in children. L-carnitine (levocarnitine), sometimes classified as an essential amino acid, is vital to mitochondrial utilization of fatty acids and can be helpful in treating this condition. The data supporting this, however, are limited. STUDY QUESTION: The aim of the study was to illustrate the role of L-carnitine in the treatment of patients with VPA-induced hyperammonemic encephalopathy (VPE) at 2 different institutions. METHODS: Medical records of affected patients were reviewed; data collected included exposure history, clinical manifestations, physical examination, and laboratory values. RESULTS: There were 13 cases of VPE; 12 were associated with therapeutic dosing and 1 with an overdose. The maximum ammonia concentration was 557 µmol/L, and blood concentrations of VPA ranged from 68 to 600 µg/mL (therapeutic range 50-100 µg/mL). In all cases, liver function tests were normal or only mildly increased. In this study, 12 patients received a daily dose of L-carnitine 100 mg/kg, and 1 received 200 mg/kg (intravenous infusion over 30 minutes) divided every 8 hours until clinical improvement. All patients made a full recovery. None developed adverse effects or reactions, and no cases of toxicity were reported. CONCLUSION: Our series suggests that intravenous L-carnitine, at a dose of 100 mg·kg·d in 3 divided doses each over 30 minutes until clinical improvement occurs, is a safe and effective treatment in the management of VPE in children.

Review of Biguanide (Metformin) Toxicity.

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.

Novel Drugs of Abuse.

Novel drugs of abuse are synthetic illicit drugs, or analogues of known illicit drugs, that can be more potent. Novel drugs of abuse are often labeled as designer drugs, research chemicals, legal highs, or psychoactive substances. They are often sold as designated legal or nondrug products, such as incense, plant food, or bath salts, with labeling such as "Not for Human Consumption" or "For Use in Research Only." The prevalence of use of novel drugs of abuse is difficult to determine because specific drugs, compounds, and availability of these drugs are constantly evolving. Changes in chemical structures lead to heterogeneity in physiologic response and clinical symptoms, even within the same category of drug. Pediatricians and emergency medicine physicians should be knowledgeable about novel drugs of abuse and their resulting symptoms for prevention and identification of their use.

Treatment of pediatric black widow spider envenomation: A national poison center's experience.

BACKGROUND: Black widow species (Latrodectus species) envenomation can produce a syndrome characterized by painful muscle rigidity and autonomic disturbances. Symptoms tend to be more severe in young children and adults. We describe black widow spider exposures and treatment in the pediatric age group, and investigate reasons for not using antivenom in severe cases. METHODS: All black widow exposures reported to the Rocky Mountain Poison Center between January 1, 2012, and December 31, 2015, were reviewed. Demographic data were recorded. Patients were divided into 2 groups. Group 1: contact through families from their place of residence, public schools and/or cases where patients were not referred to healthcare facilities. Group 2: patient contact through healthcare facilities. RESULTS: 93 patients were included. Forty (43%) calls were in Group 1 and 53 (57%) in Group 2. Symptoms were evident in all victims; 43 (46.2%) were grade 1, 16 (17.2%) grade 2 and 34 (36.5%) grade 3, but only 14 patients (41.1%) of this group received antivenom. Antivenom use was associated with improvement of symptoms within minutes, and all treated patients were discharged within hours, without an analgesic requirement or any complications. Reasons for not receiving antivenom included: skin test positive (2/20), strong history of asthma or allergies (2/20), physician preference (2/20), non-availability of the antivenom at the health care facility (14/20). CONCLUSION: In our study, most symptomatic black widow envenomations were minor. Relatively few patients received antivenom, but antivenom use was associated with shorter symptom duration among moderate and major outcome groups.

Common Substances of Abuse.

Adolescent substance abuse remains common, with almost a third of adolescents admitting to ethanol use, and a quarter admitting to illicit drug use. It is essential for pediatricians to regularly screen adolescent patients for substance use, because early initiation of drug use has been associated with physical, behavioral, and social health risks. Adolescents abuse what is common and readily available; this includes ethanol, over-the-counter products, marijuana, and inhalants. The most common and effective clinical treatments for significant toxicity from substances of abuse is symptomatic and supportive care including hemodynamic support, respiratory support, and sedation to control psychomotor agitation.

The role of QRS complex prolongation in predicting severe toxicity in single-xenobiotic overdose.

OBJECTIVE: The QRS complex duration is commonly used to prognosticate severity, predict outcomes, and indicate treatment in overdose. However, literature to support this practice is mixed in tricyclic antidepressant overdoses and absent in non-tricyclic antidepressant overdoses. Our objective was to assess the validity of QRS complex duration as a prognostic marker in overdose. METHODS: This was a secondary analysis of cases reported to the Toxicology Investigators Consortium between January 1, 2010, and December 31, 2022. Cases were assessed to determine the six xenobiotics most associated with QRS complex prolongation. All cases involving these six xenobiotics, regardless of QRS complex duration, constituted the study cohort. Inclusion criteria were cases of patients older than 12 years old with single-xenobiotic exposures. Clinical outcomes evaluated were seizure, ventricular dysrhythmia, metabolic acidosis, and death. RESULTS: Of 94,939 total cases, diphenhydramine, amitriptyline, bupropion, quetiapine, nortriptyline, and cocaine were most associated with QRS complex prolongation. Inclusion criteria were met by 4,655 cases of exposure to these xenobiotics. QRS complex prolongation was associated with increased odds ratio of seizure in all included xenobiotics, of ventricular dysrhythmia in all included xenobiotics except nortriptyline, and of metabolic acidosis or death in all included xenobiotics except nortriptyline and quetiapine. A normal QRS complex duration had a negative predictive value of greater than or equal to 93.0 percent of developing metabolic acidosis and 98.0 percent of developing a ventricular dysrhythmia or death from the xenobiotics studied. DISCUSSION: This study demonstrates that patients with QRS complex prolongation from all six xenobiotics studied had an increased prevalence and odds of developing severe outcomes. Furthermore, patients who did not develop QRS complex prolongation were unlikely to develop a ventricular dysrhythmia, metabolic acidosis, or death. These findings were noted in six xenobiotics that mechanistically can cause QRS complex prolongation through sodium channel or gap junction inhibition. CONCLUSION: Identification of patients at risk for severe outcomes after overdose can be aided by measuring the QRS complex duration. If prospectively validated, these outcomes have implications on risk stratification, disposition level of care, and appropriateness of treatments.

Use of large language models to optimize poison center charting.

INTRODUCTION: Efficient and complete medical charting is essential for patient care and research purposes. In this study, we sought to determine if Chat Generative Pre-Trained Transformer could generate cogent, suitable charts from recorded, real-world poison center calls and abstract and tabulate data. METHODS: De-identified transcripts of real-world hospital-initiated poison center consults were summarized by Chat Generative Pre-Trained Transformer 4.0. Additionally, Chat Generative Pre-Trained Transformer organized tables for data points, including vital signs, test results, therapies, and recommendations. Seven trained reviewers, including certified specialists in poison information and board-certified medical toxicologists, graded summaries using a 1 to 5 scale to determine appropriateness for entry into the medical record. Intra-rater reliability was calculated. Tabulated data was quantitatively evaluated for accuracy. Finally, reviewers selected preferred documentation: original or Chat Generative Pre-Trained Transformer organized. RESULTS: Eighty percent of summaries had a median score high enough to be deemed appropriate for entry into the medical record. In three duplicate cases, reviewers did change scores, leading to moderate intra-rater reliability (kappa = 0.6). Among all cases, 91 percent of data points were correctly abstracted into table format. DISCUSSION: By utilizing a large language model with a unified prompt, charts can be generated directly from conversations in seconds without the need for additional training. Charts generated by Chat Generative Pre-Trained Transformer were preferred over extant charts, even when they were deemed unacceptable for entry into the medical record prior to the correction of errors. However, there were several limitations to our study, including poor intra-rater-reliability and a limited number of cases examined. CONCLUSIONS: In this study, we demonstrate that large language models can generate coherent summaries of real-world poison center calls that are often acceptable for entry to the medical record as is. When errors were present, these were often fixed with the addition or deletion of a word or phrase, presenting an enormous opportunity for efficiency gains. Our future work will focus on implementing this process in a prospective fashion.

Acute exposure to hydrazine reported to four United States regional poison centers: reconsidering a paradigm.

INTRODUCTION: Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have been taken due to concern for severe toxicity. This study seeks to better understand manifestations of acute occupational exposures to hydrazine to guide recommendations for management. MATERIALS AND METHODS: A retrospective database review of records from four United States regional poison centers was conducted of all human exposures to hydrazine, monomethylhydrazine, or 1,1-dimethylhydrazine over two decades. Following case abstraction, descriptive statistics were performed to characterize demographics, manifestations, treatments, and outcomes. RESULTS: One hundred and thirty-five cases were identified, and most were adult males exposed to inhaled hydrazine propellant vapors. Fifty-seven percent of patients were asymptomatic following exposure; otherwise, common symptoms were dyspnea, throat irritation, cough, ocular irritation, and headache. All patients were evacuated or received decontamination, with a few reports of symptomatic treatments, including oxygen supplementation and salbutamol (albuterol). Patients usually recovered quickly and were released after a brief healthcare facility evaluation or observed locally. No patients developed delayed symptoms. Symptoms of severe toxicity were not observed, and there were no deaths. DISCUSSION: Acute exposures to hydrazines during operations within the aerospace industry appear to be limited primarily to mucosal and mild pulmonary irritation without significant neurologic, hepatic, or hematologic toxicity. These findings are contrary to previously established expectations and may be related to low-level exposures or possibly due to current emergency countermeasures. CONCLUSIONS: Care in occupational hydrazine exposure will focus on evacuation, decontamination, and symptomatic management of chemical irritant properties of hydrazines. It is reasonable to manage mild cases outside of a healthcare facility. Continued endeavors in human space exploration and habitation will increase the risk of these exposures, making it imperative that clinicians be comfortable with the care and management of these patients.

The Clinical Toxicology Recommendations Collaborative: purpose, organization, and methodology.

INTRODUCTION: Scientific societies aim to provide a collective voice and unified stance on important issues. The Clinical Toxicology Recommendations Collaborative was formed in 2016 to develop evidence- and consensus-based recommendations for the management of patients exposed to common and/or serious poisonings for which the management is unclear or controversial. ORGANIZATION: The Clinical Toxicology Recommendations Collaborative is led jointly by the American Academy of Clinical Toxicology, the Asia Pacific Association of Medical Toxicology, and the European Association of Poison Centres and Clinical Toxicologists. The Governance Committee is chaired by a Past-President of one of these Societies and comprised of the six Presidents and Immediate Past-Presidents of the three Societies. A Steering Committee oversees the process of each project workgroup. METHODOLOGY: The overall process is guided by standards set forth by the Institute of Medicine for developing trustworthy guidelines and the Appraisal of Guidelines for Research and Evaluation Instrument. Systematic reviews are produced using the framework set in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Workgroup members jointly review the evidence and prepare statements on which they vote anonymously using a 9-point Likert scale. A two-round modified Delphi method is used to reach a consensus on clinical recommendations using the RAND/UCLA Appropriateness Method. Final recommendations are approved by unanimous consent of the workgroup and are expressed as both levels of evidence and strength of recommendations. LIMITATIONS: The major limitations of the Clinical Toxicology Recommendations Collaborative process centre around the amount and quality of evidence, the assessment of that evidence, and the voting of the panel. CONCLUSIONS: By using a transparent evidence- and consensus-based approach to produce systematic reviews and clinical recommendations, the Clinical Toxicology Recommendations Collaborative aims to create an international framework for clinical toxicology education and decision-making and foster positive change for the benefit of poisoned patients.