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Introduction: The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis., Methods: This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted., Results: Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40., Discussion: The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap., Conclusions: In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 27. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

We report a case of Western Gaboon viper (Bitis rhinoceros) envenomation in which the patient's symptoms progressed despite treatment with North American crotalid antivenom but improved after receiving South African Institute for Medical Research (SAIMR) polyvalent antivenom. A 59-year-old man was hospitalized after reportedly being bitten by a Gaboon viper (Bitis gabonica). On arrival, he had normal vital signs, two puncture wounds on his left hand, and edema distal to the wrist. The hospital contacted the local poison center who conveyed that crotalid antivenom would be ineffective and recommended transfer to a snakebite center for species-appropriate antivenom. However, this recommendation was disregarded. Initial laboratory tests 2 hours after envenomation revealed a platelet count of 77 x 10 9 /L; other parameters were normal. He received six vials of crotalid antivenom (CroFab®) followed by three maintenance doses (total 12 vials). The next morning, swelling had progressed proximal to the elbow and platelets decreased to 37 x 10 9 /L. He was subsequently transferred and received SAIMR polyvalent antivenom. Six hours later, his platelets were 130 x 10 9 /L. The next morning, his swelling had significantly improved. He was discharged the following day. After discharge, it was discovered that the snake was a Bitis rhinoceros. Bitis gabonica and Bitis rhinoceros are popular captive snakes in the United States. Bitis rhinoceros was formerly a sub-species of B. gabonica, and they are often referred to interchangeably. Their venoms cause tissue edema, coagulopathy, and in severe cases, hemorrhage, dysrhythmias, and death. Antivenom is not widely available in the United States often necessitating patient transfer or antivenom delivery. This case addresses the question of whether crotalid antivenom, which is ubiquitous in the United States, can treat B. gabonica and B. rhinoceros envenomations and highlights the need for consultation with a poison center to facilitate administration of species-appropriate antivenom., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Aberrant right subclavian artery (ARSA) is the most common of the aortic arch anomalies, occurring in .5% to 1% of the population. There is no standardized follow up protocol, especially in the asymptomatic cases. The purpose of the present study was to evaluate the natural history of ARSA and the role of serial CT scans. Methods: This is a single-center retrospective study of patients with ARSA depicted on chest computed tomography (CT) scans between February 2013 and July 2022. Data were collected from their medical records. Measurements of the aorta at different segments including the aortic diameter at the orifice of ARSA, and ARSA at ostium followed by 1 cm intervals were collected, as well as for follow-up CT scans. Results: 65 patients were diagnosed with ARSA, 70.8% of whom were women. The average age for the cohort was 58.569 ± 16.99 years. The median follow up time was 4 years (range 0-10 years), KM estimated survival after ARSA diagnosis at 1 and 5 years as 97% and 93%, respectively. Nineteen patients had a second CT scan and were included in the morphological CT dynamic analysis, on average of 29 ± 27 months apart (range 7-108). The mean ARSA diameter at origin was larger in the second scan 16.91 ± 4.31 mm compared to the initial scan 16.31 ± 4.96 mm, ( P = .04).The mean aortic arch diameter in the first and second CT were 28.54 ± 4.24 and 29.64 ± 5.14 ( P = .10), respectively. All other measurements did not disclose any significant enlargement over time. Conclusions: Our cohort demonstrate a benign natural history of ARSA with slow growth rates. However, due to our small sample size we can't draw a clinically sound recommendation on the need for imaging follow up, and further larger cohort with longer follow up interval are required., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Many hospitals are unable to determine toxic alcohol concentrations in a clinically meaningful time frame. Thus, clinicians use surrogate markers when evaluating potentially poisoned patients., Index Case: A patient presented after an intentional antifreeze (ethylene glycol) ingestion with an osmol gap of -10.6 that remained stable one hour later. Further investigation revealed that the serum osmolality was calculated and not measured. The true osmol gap was 16.4, which correlated to a measured ethylene glycol concentration of 808 mg/L (80.8 mg/dL, 13.0 mmol/L)., Survey: A telephone survey of hospital laboratories in our catchment area was performed to investigate the potential for similar events., Results: Thirty-eight (47 percent) hospitals responded. No laboratories were able to test for toxic alcohols. One hospital (2.6 percent) reported routinely calculating osmolality based on chemistries, while two hospitals (5.3 percent) reported scenarios in which this might occur. Thirty-five (92.1 percent) hospitals could directly measure osmolality. Two hospitals (5.3 percent) were reliant on outside laboratories for osmolality measurement., Limitations: The 47 percent response rate and one geographic area are significant limitations., Discussion: Over 10 percent of hospitals that responded could have significant difficulty assessing patients with toxic alcohol ingestion., Conclusions: Until the standard of rapidly obtaining toxic alcohol concentrations is broadly implemented, we recommend that policies and procedures be put in place to minimize errors associated with the determination of the osmol gap.

Introduction: Changes in the commercialization of nonprescription drugs have made large quantities of paracetamol available to individuals, resulting in larger overdoses than previously observed. Although most patients with paracetamol overdose can be managed with acetylcysteine, patients with a massive overdose may become critically ill earlier and fail standard antidotal therapy. Several strategies are proposed for the management of these patients, including using increased doses of acetylcysteine, extracorporeal removal, and fomepizole. However, the benefits of these strategies remain largely theoretical, with sparse evidence for efficacy in humans., Methods: This cross-sectional study surveys international practice patterns of medical toxicology providers regarding the management of a hypothetical patient with a massive paracetamol overdose., Results: A total of 342 responses from 31 different nations were obtained during the study period. Sixty-one percent of providers would have increased their acetylcysteine dosing when treating the hypothetical massive overdose. Thirty percent of respondents recommended an indefinite infusion of acetylcysteine at 12.5 mg/kg/hour after the bolus dose, whereas 20 percent recommended following the "Hendrickson" protocol, which advocates for a stepwise increase in acetylcysteine dosing to match high paracetamol concentrations at the 300 mg/L, 400 mg/L, and 600 mg/L lines on the Rumack-Matthew nomogram. Ten percent of respondents stated they would have given "double dose acetylcysteine" but did not specify what that entailed. Forty-seven percent of respondents indicated that they would have given fomepizole, and 28 percent of respondents recommended extracorporeal removal., Discussion: Our survey study assessed the approach to a hypothetical patient with a massive paracetamol overdose and demonstrated that, at minimum, most respondents would increase the dose of acetylcysteine. Additionally, almost half would also include fomepizole, and nearly one-third would include extracorporeal removal., Conclusions: There is considerable international variation for the treatment of both non-massive and massive paracetamol overdoses. Future research is needed to identify and standardize the most effective treatment for both non-massive and massive paracetamol overdoses.

Introduction: Chronic nitrous oxide use can lead to neurological findings that are clinically and radiographically identical to those found in patients with pernicious anemia, specifically subacute combined degeneration of the spinal cord and peripheral neuropathy., Case Summary: A 22-year-old man presented with lower extremity weakness and ataxia in the setting of inhaling 250 nitrous oxide cartridges two to three times weekly for two years., Images: Magnetic resonance imaging showed T2 hyperenhancement of the dorsal columns of the cervical spine from the first to the sixth vertebrae, which helped to establish a diagnosis of nitrous oxide-induced subacute combined degeneration of the spinal cord., Conclusions: Chronic nitrous oxide use should be included in the differential diagnosis of any patient with otherwise unexplained neurological complaints that localize to the dorsal columns and has the changes on magnetic resonance imaging described here.

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, β-adrenergic receptor antagonists (also known as β-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.

Introduction: High-dose insulin therapy is used in patients with calcium channel blocker and beta-adrenergic antagonist overdoses. The pharmacokinetics of insulin are scantly reported following high-dose insulin therapy. We present two cases of persistently elevated insulin concentrations following high-dose insulin therapy., Case Reports: A 50-year-old woman and a 45-year-old man experienced hypotension after overdosing on amlodipine and atenolol. They were treated with high-dose insulin therapy for 54 hours at 2 units/kilogram/hour and 48 hours at 10 units/kilogram/hour, respectively. Following termination, serum insulin elimination was studied. Insulin concentrations remained greater than 1,000 µU/mL (fasting reference 2.6-24.9 µU/mL) for longer than 4 hours (case 1) and 11 hours (case 2) and greater than 300 µU/mL for longer than 8 hours and 21 hours, respectively. Insulin concentrations decreased with apparent first-order elimination half-lives of 13.0 hours and 6.0 hours., Discussion: Following high-dose insulin therapy, insulin concentrations remained elevated for longer than expected based on normal pharmacokinetics in therapeutic dosing. Three previous cases reported insulin half-lives of between 2.2 hours and 18.7 hours. The current cases add to the existing data that insulin has a variable but prolonged half-life following high-dose insulin therapy., Conclusions: These findings suggest that patients are at prolonged risk of hypoglycemia following cessation of high-dose insulin infusions.

Introduction: Colchicine is commonly used to treat diseases like acute gouty arthritis. However, colchicine has a very narrow therapeutic index, and ingestions of > 0.5mg/kg can be deadly. We report a fatal acute colchicine overdose in an adolescent. Blood and postmortem bile colchicine concentrations were obtained to better understand the degree of enterohepatic circulation of colchicine., Case Report: A 13-year-old boy presented to the emergency department after acute colchicine poisoning. A single dose of activated charcoal was administered early but no other doses were attempted. Despite aggressive interventions such as exchange transfusion and veno-arterial extracorporeal membrane oxygenation (VA-ECMO), the patient died 8 days later. Postmortem histology was notable for centrilobular necrosis of the liver and a cardiac septal microinfarct. The patient's blood colchicine concentration on hospital days 1 (~30 hours post-ingestion), 5, and 7 was 12ng/mL, 11ng/mL, and 9.5ng/mL, respectively. A postmortem bile concentration obtained during autopsy was 27ng/mL., Discussion: Humans produce approximately 600mL of bile daily. Assuming that activated charcoal would be able to adsorb 100% of biliary colchicine, using the bile concentration obtained above, only 0.0162mg of colchicine per day would be able to be adsorbed and eliminated by activated charcoal in this patient., Conclusion: Despite supportive care, activated charcoal, VA-ECMO, and exchange transfusion, modern medicine may not be enough to prevent death in severely poisoned colchicine patients. Although targeting enterohepatic circulation with activated charcoal to enhance elimination of colchicine sounds attractive, the patient's low postmortem bile concentration of colchicine suggests a limited role of activated charcoal in enhancing elimination of a consequential amount of colchicine., (© 2023. American College of Medical Toxicology.)

Introduction: The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup defined criteria for extracorporeal toxin removal in patients with metformin poisoning. The primary objective of this study was to determine the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria. The secondary objective was to determine the performance characteristics of the EXTRIP criteria., Methods: This was a single-center retrospective analysis of metformin poisoned patients. Inclusion criteria were: suspicion of metformin poisoning with at least one of the following present: lactate concentration >5 mmol/L; pH < 7.35; or impaired kidney function. Patient data were extracted by reviewers who were unaware of the study hypothesis. Cases were analyzed based on EXTRIP criteria, whether extracorporeal toxin removal was performed, and survival. Sensitivity, specificity, negative predictive value and positive predictive value were calculated with respect to the EXTRIP criteria and survival., Results: Of 201 patients studied, 145 patients met recommended EXTRIP criteria (EXTRIP positive) and 56 patients did not (EXTRIP negative). Among patients who met recommended EXTRIP criteria, 96 received extracorporeal toxin removal and 49 did not. There was no difference in survival between these groups: 75.0% versus 73.5%, respectively ( P >0.05). All 56 patients who did not meet EXTRIP criteria, survived (negative predictive value = 100%)., Discussion: The study did not demonstrate a survival benefit for extracorporeal toxin removal in those meeting EXTRIP criteria., Conclusion: In this retrospective analysis, the recommended EXTRIP criteria had a negative predictive value for death of 100%. Further study is needed to evaluate the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria for metformin poisoning.

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR., (© 2023. The Author(s).)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Human grayanotoxin poisoning is distinctly uncommon in North America, as the predominant source of human exposure is honey made by bees pollinating rhododendron species in the Mediterranean. We present a case of confirmed grayanotoxin poisoning from honey imported from Turkey., Case Report: A 61-year-old man developed nausea, lightheadedness, and lost consciousness. Onset was 30 min after the ingestion of honey that was brought to the United States from Turkey. Emergency medical services found him bradycardic, hypotensive, and unresponsive. He was treated with atropine, saline, and oxygen, at which point his heart rate and blood pressure improved, and he regained consciousness. A similar episode several days earlier was followed by a brief unrevealing hospitalization. He was again hospitalized, and had a normal echocardiogram, telemetric monitoring, and complete laboratory studies. Grayanotoxins I and III were subsequently identified in the patient's blood, urine, and honey. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Grayanotoxins are diterpenoids found in rhododendron species, whose clinical effects span multiple organ systems including gastrointestinal, cardiac, and neurologic. Treatment is largely supportive, and a good response to atropine and intravenous fluids has been described. Laboratory confirmation of grayanotoxins is not available in a short enough turnaround time to be clinically useful during immediate management, but confirmatory testing may obviate further unnecessary evaluation. Grayanotoxins are likely to remain a rare source of poisoning in North America, but recurrent bradycardia without alternative etiology should prompt a thorough exposure history, which may reveal, as in this case, a treatable toxicologic etiology., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Context: Ethylene glycol poisoning manifests as metabolic acidemia, acute kidney injury and death. The diagnosis and treatment depend on history and biochemical tests. Glycolate is a key toxic metabolite that impacts prognosis, but assay results are not widely available in a clinically useful timeframe. We quantitated the impact of serum glycolate concentration for prognostication and evaluated whether more readily available biochemical tests are acceptable surrogates for the glycolate concentration., Objectives: The objectives of this study are to 1) assess the prognostic value of the initial glycolate concentration on the occurrence of AKI or mortality in patients with ethylene glycol exposure ( prognostic study ); 2) identify surrogate markers that correlate best with glycolate concentrations (surrogate study )., Methods: A systematic review of the literature was performed using Medline/PubMed, EMBASE, Cochrane library, conference proceedings and reference lists. Human studies reporting measured glycolate concentrations were eligible. Glycolate concentrations were related to categorical clinical outcomes (acute kidney injury, mortality), and correlated with continuous surrogate biochemical measurements (anion gap, base excess, bicarbonate concentration and pH). Receiver operating characteristic curves were constructed to calculate the positive predictive values and the negative predictive values of the threshold glycolate concentrations that predict acute kidney injury and mortality. Further, glycolate concentrations corresponding to 100% negative predictive value for mortality and 95% negative predictive value for acute kidney injury were determined., Results: Of 1,531 articles identified, 655 were potentially eligible and 32 were included, reflecting 137 cases from 133 patients for the prognostic study and 154 cases from 150 patients for the surrogate study. The median glycolate concentration was 11.2 mmol/L (85.1 mg/dL, range 0-38.0 mmol/L, 0-288.8 mg/dL), 93% of patients were treated with antidotes, 80% received extracorporeal treatments, 49% developed acute kidney injury and 13% died. The glycolate concentration best predicting acute kidney injury was 12.9 mmol/L (98.0 mg/dL, sensitivity 78.5%, specificity 88.1%, positive predictive value 86.4%, negative predictive value 80.9%). The glycolate concentration threshold for a 95% negative predictive value for acute kidney injury was 6.6 mmol/L (50.2 mg/dL, sensitivity 96.9%, specificity 62.7%). The glycolate concentration best predicting mortality was 19.6 mmol/L (149.0 mg/dL, sensitivity 61.1%, specificity 81.4%, positive predictive value 33.3%, negative predictive value 93.2%). The glycolate concentration threshold for a 100% negative predictive value for mortality was 8.3 mmol/L (63.1 mg/dL, sensitivity 100.0%, specificity 35.6%). The glycolate concentration correlated best with the anion gap ( R 2  = 0.73), followed by bicarbonate ( R 2  = 0.57), pH ( R 2  = 0.50) and then base excess ( R 2  = 0.25), while there was no correlation between the glycolate and ethylene glycol concentration ( R 2  = 0.00). These data can assist clinicians in planning treatments such as extracorporeal treatments and prognostication. Potentially, they may also provide some reassurance regarding when extracorporeal treatments can be delayed while awaiting the results of further testing in patients in whom ethylene glycol poisoning is suspected but not yet confirmed., Conclusions: This systematic review demonstrates that the glycolate concentration predicts mortality (unlikely if <8 mmol/L [61 mg/dL]). The anion gap is a reasonable surrogate measurement for glycolate concentration in the context of ethylene glycol poisoning. The findings are mainly based on published retrospective data which have various limitations. Further prospective validation studies are of interest.

Context: Ethylene glycol is metabolized to toxic metabolites that cause acute kidney injury, metabolic acidemia, and death. The treatment of patients with ethylene glycol poisoning includes competitively inhibiting alcohol dehydrogenase with ethanol or fomepizole to prevent the formation of toxic metabolites, and extracorporeal treatments such as hemodialysis to remove ethylene glycol and its metabolites. In the absence of significant metabolic acidemia or kidney injury, it is hypothesized that extracorporeal treatments may be obviated without adverse outcomes to the patient if alcohol dehydrogenase inhibitors are used., Objectives: The objectives of this study are to: (1) identify indicators predicting ADH inhibitor failure in patients with ethylene glycol poisoning treated with either ethanol or fomepizole for whom extracorporeal treatment was not performed (aside from rescue therapy, see below) ( prognostic study ), and (2) validate if the anion gap, shown in a previous study to be the best surrogate for the glycolate concentration, is associated with acute kidney injury and mortality ( anion gap study )., Methods: We conducted a systematic review to identify all reported patients with ethylene glycol poisoning treated without extracorporeal treatments but with either fomepizole ( fomepizole monotherapy ) or ethanol ( ethanol monotherapy ). Analyses were performed using both one case per patient and all cases (if multiple events were reported for a single patient). Data were compiled regarding poisoning, biochemistry, and outcomes. Treatment failure was defined as mortality, worsening of acid-base status, extracorporeal treatments used as rescue, or a worsening of kidney or neurological function after alcohol dehydrogenase inhibition was initiated. Also, we performed an analysis of previously described anion gap thresholds to determine if they were associated with outcomes such as acute kidney injury and mortality., Results: Of 115 publications identified, 96 contained case-level data. A total of 180 cases were identified with ethanol monotherapy, and 231 with fomepizole monotherapy. Therapy failure was noted mostly when marked acidemia and/or acute kidney injury were present prior to therapy, although there were cases of failed ethanol monotherapy with minimal acidemia (suggesting that ethanol dosing and/or monitoring may not have been optimal). Ethylene glycol dose and ethylene glycol concentration were predictive of monotherapy failure for ethanol, but not for fomepizole. In the anion gap study (207 cases), death and progression of acute kidney injury were almost nonexistent when the anion gap was less than 24 mmol/L and mostly observed when the anion gap was greater than 28 mmol/L., Conclusion: This review suggests that in patients with minimal metabolic acidemia (anion gap <28 mmol/L), fomepizole monotherapy without extracorporeal treatments is safe and effective regardless of the ethylene glycol concentration. Treatment failures were observed with ethanol monotherapy which may relate to transient subtherapeutic ethanol concentrations or very high ethylene glycol concentrations. The results are limited by the retrospective nature of the case reports and series reviewed in this study and require prospective validation.

Taking care of patients with agitated toxidromes can be challenging. While many will be able to be discharged from the emergency department or transferred to psychiatry following brief and simple interventions others will have life-threatening toxicity. Health care providers must develop an organized approach to the assessment and management of these patients that includes foremost the protection of the patient and staff from physical harm, prompt pharmacologic control to allow rapid assessment for life-threatening abnormalities such as hypoglycemia and hyperthermia and optimal cooling of patients with extreme temperature elevations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either "strong" or "weak/conditional") were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m 2 ]: 91 patients; low-dose [≤0.5 g/m 2 ]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate-related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: ( 1 ) suggested against extracorporeal treatments when glucarpidase is not administered; ( 2 ) recommended against extracorporeal treatments when glucarpidase is administered; and ( 3 ) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: ( 1 ) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; ( 2 ) extracorporeal treatments remove folinic acid; ( 3 ) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and ( 4 ) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity., (Copyright © 2022 by the American Society of Nephrology.)

Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as "dialyzable" for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence)., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations., Objectives: The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal?  Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal., Methods: A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase ( via Ovid), CINAHL ( via EBSCO), BIOSIS Previews ( via Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations.  One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study., Results: From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 in vitro studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% ( n  = 1006 individuals), beyond two hours in 36% ( n  = 491 individuals), and beyond 12 h in 4% ( n  = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% ( n  = 2359 individuals) and beyond two hours in 36% ( n  = 484) of individuals., Conclusions: This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death.  Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.

Baclofen toxicity results from intentional self-poisoning (acute baclofen poisoning) or accumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Use of extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Aims: Two guidelines for haemodialysis in lithium poisoning, one from the Extracorporeal TReatments in Poisoning (EXTRIP) workgroup and a single centre retrospective one (Paris) differ. We compared outcomes in lithium poisoning based on these criteria with a primary outcome of worsening neurological symptoms in patients for whom EXTRIP and Paris criteria were discordant., Methods: Poison centre data were queried for lithium poisoned patients for whom haemodialysis was either recommended or performed. Patients were categorized according to EXTRIP and Paris criteria and excluded if the peak lithium concentration was <1.2 mmol/L or if neurological follow-up was unavailable. Comparative analyses were only performed when both criteria could be assessed., Results: In total, 219 patients were analysed. Paris criteria were met in 70 and EXTRIP criteria in 178. Forty two patients were excluded because Paris criteria could not be evaluated. When Paris and EXTRIP both supported haemodialysis, 50/57 (88%) of patients who received haemodialysis improved, as did all 3 who did not receive haemodialysis. When Paris and EXTRIP did not support haemodialysis, all nondialysed patients did well. Among the 86 patients for whom EXTRIP supported haemodialysis but Paris did not, 4/19 (21%) patients not dialysed deteriorated (P = .02; odds ratio = 8.7, 95% confidence interval = 1.5-51.8), 1 of whom died. All 8 patients for whom Paris criteria supported haemodialysis but EXTRIP did not were dialysed and improved., Conclusions: When the EXTRIP and Paris criteria are discordant, EXTRIP criteria outperforms the Paris criteria at identifying potentially ill patients who might benefit from haemodialysis., (© 2021 British Pharmacological Society.)

Context: Anion gap metabolic acidosis (AGMA) is common in patients presenting for emergency care. While some disease processes and ingestions are easily excluded, diagnosing toxic alcohol (TA) ingestion can be challenging. This is especially true if drug concentrations are not readily available, which forces clinicians to rely on surrogate markers. Like TA ingestion, alcoholic ketoacidosis (AKA) produces an elevated osmol gap and an AGMA. The aim of this study was to identify risk factors suggestive of AKA when TA ingestion was the primary alternative differential diagnosis. We hypothesized that the odds of an AKA diagnosis would increase as ethanol concentration increased., Methods: This was a retrospective analysis of data from 2000 through 2019 from a single US Poison Control Center. Records were reviewed to identify cases coded as "methanol" or "ethylene glycol"; or coded as "alcohol" or "ethanol with acidosis." The case definition for AKA required: (1) documented alcohol use disorder; (2) urine or serum ketones or elevated blood beta-hydroxybutyrate concentration; (3) anion gap ≥ 14 mmol/L. The inclusion criterion for TAs was a detectable methanol or ethylene glycol concentration., Results: Of 699 patients screened, 86 were diagnosed with AKA and 36 were diagnosed with TA ingestion. As ethanol concentration increased, the odds of an AKA diagnosis significantly increased (OR = 1.016, 95% CI 1.002-1.031, p  = .03)., Conclusions: In this retrospective analysis, the odds of diagnosing AKA instead of TA ingestion increased as ethanol concentration increased. The limited ability of common clinical factors to differentiate these diagnoses highlights the need to obtain quantitative TA concentrations in real time. Until prospective validation, interpretation of ketone concentrations and toxic alcohol concentrations (when available) will continue to guide decision making.

Background: β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning., Methods: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods., Results: A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations., Conclusions: BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.

Background: Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning., Methods: We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods., Results: A total of 83 publications (6 in vitro and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR., Conclusions: Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence = C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABA A receptor agonists (weak recommendation, very low quality of evidence)., (© 2021 Pharmacotherapy Publications, Inc.)

Introduction: The term "lactic acidosis" reinforces the misconception that lactate contributes to acidemia. Although it is common to discover an anion gap acidosis with a concomitant elevated lactate concentration, the two are not mutually dependent., Case Report: Here we describe two patients exhibiting high lactate concentrations in the setting of metabolic alkalemia., Conclusion: Lactate is not necessarily the direct cause of acid-base disturbances, and there is no fixed relationship between lactate and the anion gap or between lactate and pH. The term "metabolic acidosis with hyperlactatemia" is more specific than "lactic acidosis" and thus more appropriate.

Introduction: Severe baclofen toxicity can result in respiratory failure, hemodynamic instability, bradycardia, hypothermia, seizures, coma, and death. While hemodialysis (HD) is well-described in treating acute baclofen toxicity in patients with end-stage kidney disease or acute kidney injury, the utility of HD for patients with normal kidney function is uncertain. Implementing HD to speed recovery after a large acute baclofen ingestion is appealing, considering: (a) potential for prolonged coma and ventilator-associated morbidity, and (b) baclofen's low protein-binding, low molecular-weight, and moderate volume of distribution., Methods: We report a 51 kg, 14-year-old girl who presented to the emergency department (ED) with hypotension, obtundation, and status epilepticus after an intentional ingestion of 1200 mg baclofen. Her post-intubation neurologic examination was concerning for coma. A 14-hour post-ingestion baclofen concentration was 882 ng/mL (therapeutic range 80-400 ng/mL). Three urgent-HD sessions were performed to reduce her time on the ventilator., Results: The total baclofen removed in the first three-hour HD session was 3.05 mg. The total urinary elimination of baclofen 42 mg over 24-hours on day one. She was discharged without neurologic deficits to psychiatry on day-14., Conclusion: In this case, the amount of baclofen recovered during HD is negligible in comparison to the amount cleared by kidney elimination in this patient with normal kidney function.

Objective: This study was designed to determine the fatality rate of suspected cyclopeptide-containing mushroom ingestions reported to the National Poison Data System (NPDS)., Background: Although silibinin reportedly improves survival in suspected cyclopeptide-containing mushroom ingestions, the greater than 20% untreated fatality rate that is often cited is based on decades-old data. An ongoing open-label silibinin trial will likely use historical cases as comparators. A recent single poison control center (PCC) study showed a fatality rate of 8.3%. This study was designed to validate those findings in the NPDS., Methods: This study was an 11-year (1/1/2008-12/31/2018) retrospective review of suspected cyclopeptide-containing mushroom ingestions reported to NPDS. Inclusion and exclusion criteria were the same as the ongoing silibinin trial: Age >2-years-old; history of eating foraged mushrooms; gastrointestinal symptoms within 48 h of mushroom ingestion; and aminotransferases above the upper limit of normal within 48 h after ingestion. Each original participating PCC confirmed eligibility, diagnosis, treatment, and outcome on included cases., Results: During the study period, 8,953 mushroom exposures were reported to NPDS, of which 296 met inclusion criteria. The PCC survey response rate was 60% (28/47 PCCs), and the individual case response rate was 59% (174/296). Twenty-six cases were subsequently excluded leaving 148 included cases. The overall mortality rate was 8.8% (13/148). Mortality in silibinin/silymarin-treated vs untreated cases was 9.5% (4/42), vs 8.5% (9/106), respectively. A mycologist identified mushrooms in 16.9% of cases (25/148), of which 80% (20/25) were cyclopeptide-containing. Among these confirmed cases, the mortality rate was 10% (1/10) in both silibinin/silymarin-treated and untreated cases., Conclusions: The contemporary mortality rate of patients with presumed cyclopeptide-mushroom poisoning is only 8.8%. This likely represents improved supportive care for patients with acute liver injury and should be considered the current standard for historical controls in the United States.