Acute Ingestions Research Articles

Utility of iron concentration two to four hours post ingestion in predicting toxicity

IntroductionIron products are widely available over the counter and have the potential to cause serious toxicity. Iron concentrations can be used to prognosticate and guide treatment during acute ingestions. Traditionally, a concentration of 350 μg/dL with symptoms, or 500 μg/dL without symptoms, is considered toxic and will likely need treatment to prevent decompensation. It is generally recommended that an iron concentration is obtained at least 4 h after exposure to provide adequate absorption time and avoid falsely low iron concentrations. Despite this, many iron overdoses have concentrations drawn immediately upon patient presentation. The utility of an iron concentration drawn before 4 h in assessing exposure risk is not clear. The purpose of this study is to determine if patients' symptoms and iron concentrations obtained between 2 and 4 h can predict the development of iron concentrations after 4 h. MethodsThis is a single-center, retrospective study of patient cases with a primary ingestion of oral iron reported to a Regional Poison Center from January 1, 2015 to January 1, 2020. The primary outcome is the incidence of an iron concentration of 350 μg/dL or greater at or beyond 4 h. Secondary outcomes include the incidence of antidotal deferoxamine administration, incidence of iron concentration > 500 μg/dL, incidence of positive findings on abdominal radiography, and time to highest reported iron concentration. ResultA total of 75 patients were included in this study. No patients who developed at most minor symptoms (abdominal discomfort, nausea, vomiting, or diarrhea without evidence of systemic toxicity) and had a 2-to-4-h concentration ≤ 300 μg/dL symptoms had a subsequent concentration > 350 μg/dL (negative predictive value [NPV] 100 %). Deferoxamine was used to treat five patients, all reached concentrations of >300 μg/dL 2–4-h post-ingestion. ConclusionPatients with only minor GI symptoms and an iron concentration of ≤300 μg/dL between 2 and 4-h post ingestion are unlikely to develop further toxicity. In this case series, a concentration of 300 μg/dL or less between 2 and 4 h was the ideal cutoff to predicting subsequent potentially toxic concentrations, with a sensitivity of 100 % and a specificity of 54 %.

Demographics and Clinical Characteristics Assessment of Severe Acute Toxic Ingestions in Pediatric Patients: A Single-Center Study in Jilin Province of China.

This study aimed to describe the demographic and clinical characteristics of severe acute toxic ingestions in children in Jilin Province and provide a reference for seeking effective measures to prevent poisoning accidents. The clinical data of patients diagnosed with acute toxic ingestions and who presented with severe life-threatening symptoms or organ dysfunction at the Pediatric Intensive Care Unit of the First Hospital of Jilin University were retrospectively analyzed. Patients with incomplete clinical medical records, unclear toxic substance, and loss to follow-up within 6 months of discharge are excluded. We sorted out these children's demographic characteristics, types of poisoning, clinical manifestations, treatment process, and follow-up, etc. This study enrolled 141 cases with no significant differences in sex and region; adolescents accounted for 44.68%. The most common poisons were pesticides and insecticides for rural areas and internal medication for urban areas. With poisoning details as a grouping variable, there was no statistical difference between sex groupings (χ2 = 6.018, P = 0.198) and no difference between region groups (χ2 = 3.775, P = 0.289). However, there were statistical differences between age groups (χ2 = 28.22, P = 0.001). In this research, patients younger than 6 years are mainly unintentionally poisoned, whereas the suicide rate of the urban group (P < 0.05), adolescents (P < 0.01), and girls (P < 0.01) has increased significantly; moreover, the suicide group is more likely to take more overdose medication or pesticides and insecticides (P < 0.01). In addition, there was a statistical difference between suicide and length of intensive care unit stay (r = 0.268, P < 0.01). A total of 90.78% of the patients were successfully discharged after comprehensive treatment. Children aged younger than 12 years had good psychological and intellectual development during the follow-up period, whereas adolescents diagnosed with depression often required long-term psychological and medication intervention. This study identified poisoning details in different ages, regions, and sex of acute severe oral poisoning in children from Jilin Province. The results presentation of different prevention priorities should vary among children of different ages and emphasize adolescent suicide being a reality in Jilin Province. There is an urgent need for further culture-specific research in this area.

Strychnine Poisoning: Literature Review

Strychnine poisoning is an quite unusual but a serious poisoning in which convulsions are the major threat to life. Convulsions are predominantly noted at the spinal level, and the key to recognizing this poison is observation of convulsive activity in the awake patient without a postictal phase. Successful treatment requires aggressive airway control and treatment of seizures with benzodiazepines or barbiturates. Neuromuscular blockade may be required. Gastrointestinal decontamination is usually indicated in recent acute ingestions but may precipitate convulsions. Recovery from strychnine poisoning is usually complete and rapid if treatment is aggressive.

Oral Capecitabine Exposures and Use of Uridine Triacetate: A 20-Year Retrospective Analysis.

Capecitabine is an oral prodrug of 5-fluorouracil. Toxicity can occur during therapy as well as acutely with overdose and particular genetic susceptibilities. Uridine triacetate is an effective antidote if given within 96h of exposure. This study seeks to characterize accidental and intentional capecitabine exposures and uridine triacetate use, about which little has been published. A retrospective review of capecitabine exposures from 30 April 2001 to 31 December 2021 reported to a statewide poison control center was performed. All single-substance oral exposures were included. In total, 81 of 128 reviewed cases were included, with a median age of 63years. In total, 49 were acute-on-chronic exposures and 32 were acute exposures in capecitabine-naïve patients, 29 of which were accidental. Fifty-six (69%) were managed at home. Of these, none later recontacted the poison control center to report symptoms or were known to have later had healthcare facility evaluations. Of the 25 cases presenting for healthcare facility evaluation, 4 were acutely symptomatic. Thirteen were eligible for uridine triacetate, and six received it; no new or progressive toxicity was reported after. Three developed mild latent toxicity; otherwise, no morbidity or mortality was reported. Accidental acute-on-chronic and acute ingestions of capecitabine appear to be well tolerated; most cases were managed at home. Unfortunately, little is known regarding the threshold at which toxicity may present following exposures. The threshold may vary individually given genetic susceptibilities. Management was heterogeneous, likely reflecting inadequate guidelines. Further research is needed to better delineate at-risk populations and treatment strategies.

Performance of computed tomography and its reliability for the diagnosis of transmural gastrointestional necrosis in a setting of acute ingestion of predominantly strong acid substances in adults

Objectives Computed tomography has become a critical component in evaluating adult patients with acute caustic ingestions and an alternative to endoscopy for detecting transmural gastrointestinal necrosis. This study assessed the performance and reliability of computed tomography findings of transmural gastrointestinal necrosis, given that the presence of the disease potentially signifies the need for surgery. Methods A retrospective database search was performed to identify consecutive adult patients with acute caustic ingestions who had computed tomography with endoscopy or surgery within 72 h of admission. Eight physicians reinterpreted computed tomography in two separate rounds. Diagnostic performance utilized eight rounds of radiologists' reinterpretations against reference endoscopic or surgical grades. Intra- and interobserver agreements were calculated. Results Seventeen patients (mean age, 45.6 years; 9 men; 46 esophageal and 34 gastric segments; 16 ingested strong acid substances) met the inclusion criteria. Eight patients (10 esophageal and 13 gastric segments) had transmural gastrointestinal necrosis. The highly differentiating findings between those with and without transmural gastrointestinal necrosis were esophageal wall thickening (100% vs. 42%, P = 0.001; 100% sensitive), gastric abnormal wall enhancement and fat stranding (100% vs. 57%, P = 0.006; 100% sensitive), and gastric absent wall enhancement (46% vs. 5%, P = 0.007; 100% specific). The intra- and interobserver percentage agreements were 47–100%, and 54–100%, which increased to 53–100%, and 60–100%, respectively, when considering only radiologists’ reinterpretations. Conclusions In a very small sample of adults who primarily ingested acid, contrast-enhanced computed tomography performed well when interpreted by a panel of radiologists.

Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19

Background US poison control centers reported increased cases of ivermectin toxicity during the COVID-19 pandemic. Previous descriptions of ivermectin toxicity have evaluated heterogeneous groups with a variety of ivermectin sources and dosage patterns. We sought to compare the clinical effects of ivermectin toxicity in patients taking human- vs. veterinary-formulations and acute- vs. chronic-ingestion patterns. Methods We performed a retrospective analysis of cases from the Oregon Poison Center of ivermectin exposures for the prevention or treatment of COVID-19 that resulted in a healthcare visit over a 24-week period (14 August 2021 − 31 January 2022). Results We identified 37 cases of ivermectin toxicity. The median age of patients was 64 years, and most patients were male. The majority of patients were hospitalized (21) or treated in an emergency department (13). A minority were treated in an outpatient setting (3) and one patient died. Seventeen ingested veterinary formulations and fifteen ingested prescription tablets. Patients reported taking ivermectin for treatment (23) and prevention (14) of COVID-19. Clinical effects included neurotoxicity (30), gastrointestinal symptoms (14), and musculoskeletal complaints (7). Patients taking veterinary products took higher doses of ivermectin and had higher rates of altered mental status than those taking prescription tablets. Patients taking ivermectin chronically took smaller doses (daily dose of 13.5 mg) over a prolonged period (median 3.8 weeks) and developed toxicity that was milder than those with acute ingestions. Conclusion Ivermectin toxicity developed in predominantly male patients >60 years old who ingested higher than recommended doses and developed neurologic symptoms. Patients who took a veterinary formulation of ivermectin ingested large single doses or large daily doses for several days and developed rapid onset of neurotoxicity. Patients with chronic toxicity developed milder symptoms and tended to take typical therapeutic doses, but continued therapy for weeks rather than days.

QTc Prolongation in Poison Center Exposures to CredibleMeds List of Substances with "Known Risk of Torsades de Pointes".

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.

2020 Annual Report of the Kansas Poison Control Center at The University of Kansas Health System.

IntroductionThis is the 2020 Annual Report of the Kansas Poison Control Center (KSPCC) at The University of Kansas Health System. The KSPCC receives calls from the public, law enforcement, healthcare professionals, and public health agencies.MethodsEncounters reported to the KSPCC from January 1, 2020 through December 31, 2020 were analyzed for caller location, demographics, exposure substance, nature of exposure, route of exposure, interventions, medical outcome, and location of care. Encounters were classified as human or animal exposure, confirmed non-exposure, or information call (no exposure).ResultsThere were 19,780 total encounters, including 18,492 human exposure cases. These cases were primarily female (53.6%, n = 9,911) and pediatric (19 years of age or less; 59.5%, n = 10,995). Acute cases (82.7%, n = 15,294), unintentional exposures (73.8%, n = 13,643), and ingestions (85.9%, n = 15,901) were most common. The most common reported substance was household cleaning products (n = 937) in pediatric (children ≤ 5) and analgesics (n = 1,335) in adults. An increase in exposures to disinfectants and household cleaning products was seen. Moderate (n = 1,812) or major (n = 482) clinical outcomes were seen in 12.4% of cases. There were 18 deaths in 2020 reported to the KSPCC.ConclusionsOver 18,400 exposures were managed by the KSPCC in 2020. Pediatric exposures remained the most common encounter. An increase in exposures to disinfectants and other household cleaning products was seen. This report supported the continued value of the KSPCC to both public and acute healthcare in the state of Kansas.

Activated Charcoal and Bicarbonate for Aspirin Toxicity: a Retrospective Series.

Aspirin overdose causes acid-base disturbances and organ dysfunction. Management is guided by research reported over 50years ago when chronic aspirin toxicity was common and accounted for significant morbidity. We investigate our experience of aspirin overdose and the effectiveness of charcoal and bicarbonate administration over 20years. This is a retrospective series of acute aspirin overdosefrom two toxicology units from January 2000 to September 2019. Acute aspirin ingestions > 3000mg were identified in each unit's database. Excluded were cases of chronic exposure, hospital presentation > 24 hours after ingestion, and cases without a salicylate concentration. Included in our analysis wasdemographic data, clinical effects, investigations, complications, and treatment. There were 132 presentations in 108 patients (79 females (73%)). The median age was 28years (range: 13-93years). The median dose ingested was 7750mg (IQR: 6000-14,400mg). There were 44 aspirin-only ingestions. Mild toxicity (nausea, vomiting, tinnitus or hyperventilation) occurred in 22 with a median dose of 160mg/kg. Moderate toxicity (acid-base disturbance, confusion) occurred in 16 with a median ingested dose of 297mg/kg. There were no cases of severe toxicity (coma or seizures) due to aspirin alone. The median peak salicylate concentration was 276mg/L (IQR: 175-400mg/L, range: 14-814mg/L). There was a moderate association between dose ingested and peak concentration (Pearson r = 0.58; 95% CI 0.45-0.68). Activated charcoal was administered in 36 (27%) cases, which decreased the median peak salicylate concentration (34.2 to 24.8mg/L/g (difference: 9.4, 95% CI: 1.0-13.1)). Bicarbonate was administered in 34 (26%) presentations, decreasing the median apparent elimination half-life from 13.4 to 9.3h (difference: 4.2h, 95% CI: 1.0-6.5h). Acute aspirin overdose caused only mild to moderate effects in this series. Early administration of activated charcoal decreased absorption and use ofbicarbonate enhancedelimination.

Single bag high dose intravenous N-acetylcysteine associated with decreased hepatotoxicity compared to triple bag intravenous N-acetylcysteine in high-risk acetaminophen ingestions

Introduction There is controversy that the triple bag intravenous (IV) N-acetylcysteine (NAC) regimen may be underdosing the sickest patients in its current, common usage. We hypothesize that a higher dose IV NAC regimen improves some outcomes. Methods We conducted a poison center based retrospective observational study from January 1, 2016 to December 31, 2017 comparing a single bag higher dose IV NAC regimen (150 mg/kg over 1 h, 15 mg/kg/hour) to the triple bag IV NAC regimen (150 mg/kg over 1 h, 12.5 mg/kg/hour for 4 h, 6.25 mg/kg/hour). In a high-risk population of patients with acetaminophen ingestion (defined as multiplication product ≥ 10,000 mg/L IU/L, not acute ingestions receiving NAC within 8 h, and not hepatotoxic on first contact), we evaluated the rate of hepatotoxicity, peak transaminase, and rate of laboratory coagulopathy. Results 89 patients met the inclusion criteria. 12 of the 23 patients (52%) who received triple bag NAC became hepatotoxic and 10 (43%) became coagulopathic, while only 19 of 66 patients (29%) who received single bag NAC became hepatotoxic and 15 (23%) became coagulopathic; p = .043 and .057, resp. Mean peak transaminase was 4481 IU/L vs 2143 IU/L in those receiving triple bag NAC vs single bag NAC, difference of means 2338 IU/L; p = .026. Conclusion In this exploratory study of a high-risk population of patients with acetaminophen ingestions, the single bag IV NAC regimen was associated with lower peak transaminase and fewer patients becoming hepatotoxic as compared to the triple bag IV NAC regimen.

Calcium Carbonate for Elemental Lead Ingestions: Effect of Alkalinization on Elemental Lead Solubility in a Simulated Gastric Environment.

Acute ingestion of elemental lead foreign bodies has resulted in multiple pediatric deaths. Elemental lead is relatively insoluble at alkaline pH. Furthermore, calcium decreases lead absorption by interfering with the lead absorptive receptor. We hypothesize that alkalinization of gastric fluid with an oral calcium-containing agent, such as calcium carbonate, will decrease lead solubility, thus reducing the potential for systemic lead absorption and toxicity. This was an in vitro controlled study. One lead sphere (00 buckshot, cast 30 days prior) was randomly placed in each of ten tubes containing 20 mL simulated gastric fluid, with five tubes having 500 mg calcium carbonate added at 20 min and 140 min. We measured the fluid pH and the lead concentrations hourly for 4 h. We compared the median amount of total lead liberated after 4 h between the two groups using the Mann-Whitney U test. The pH of the gastric fluid only tubes remained 1 at every measurement, and the pH of the gastric fluid + calcium carbonate tubes was 6 at every measurement. At hour 4, the total amount of lead liberated in the soluble fraction in the control group vs the calcium carbonate group was 850 vs 12.4 mcg (95% CI for absolute difference: 605-964 mcg; p = 0.0079). Calcium carbonate antacid alkalinizes gastric fluid pH and dramatically decreases the total amount of solubilized lead by 60-fold. This project lends foundational evidence to a low-cost, widely available, pre-hospital strategy to decrease lead absorption after acute elemental lead ingestions.

Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose (2NAC study)

BackgroundPrevious studies of paracetamol overdose treatment show that a 2-bag, 20-h intravenous (IV) acetylcysteine regimen decreased the incidence of non-allergic anaphylactic reactions compared to the 3-bag, 21 h IV regimen, but have not examined efficacy of the 20-h 2 bag regimen. MethodsThis was a multi-centre observational study of paracetamol overdose presentations treated with a 2-bag IV acetylcysteine regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) compared to a 3-bag regimen, performed from 2009 to 2019. Patients were referred from the emergency department to the inpatient toxicology units for continued management. For the primary non-inferiority analysis: subjects had single, acute ingestions, a serum paracetamol-concentration performed 4 to 8-h post-ingestion. The primary outcome was development of acute liver injury (ALI), defined as peak ALT>150 U/L; and > double admission baseline ALT (for presentations within 24 h post-overdose). Secondary outcomes included adverse reactions to acetylcysteine (cutaneous and systemic). FindingOut of 6419 paracetamol overdoses, 2763 received acetylcysteine. For the primary analysis, 1003 received the 2-bag and 783 the 3-bag acetylcysteine regimen. When presentation bloods were performed 4 to 8-h post-overdose, 21 (3.1%) developed ALI with the 2-bag regimen vs 16 (2.9%) with the 3-bag regimen (Difference: 0.2%, 95%CI:-1.6 to 2.2). The incidence of hepatotoxicity was: 1.2% (n = 8) with the two-bag regimen and 1.6% (n = 9) with the three-bag regimen (Difference -0.4%, 95%CI -1.75, 0.91). When presentation bloods were performed 8 to 24-h post-overdose, 70 (21%) developed ALI with the 2-bag regimen vs 46 (23%) with the 3-bag regimen (Difference: -2%, 95%CI -9.12 to 5.36). There were significantly less cutaneous and systemic non-allergic anaphylactic reactions recorded after treatment with the two-bag than the three-bag regimen (1.3% [n = 17] and 7.1% [n = 65], Difference: -5.8%, 95%CI -7.6 to -4.0, p < 0.0001), respectively. InterpretationA two-bag intravenous acetylcysteine regimen was found to be non-inferior to the three-bag regimen with regards to efficacy in preventing acute liver injury for early presentations of paracetamol overdose. No important differences were seen for any other presentations. The two-bag regimen also decreased the incidence of both non-allergic anaphylactic reactions and gastrointestinal adverse events from acetylcysteine treatment. FundingAW is funded by a National Health and Medical Research Council (NHMRC) Early Career Fellowship ID 1159907. GI is funded by a NHMRC Senior Research Fellowship ID 1061041. The NHMRC had no role in the design, writing of this manuscript. The corresponding author (AW) had full access to all the data in the study and final responsibility for the decision to submit the manuscript for publication.

Outcomes of acute exploratory pediatric lithium ingestions

Objectives: To date, very little literature describes the outcomes of acute unintentional ingestions of lithium in young children. This study aimed to describe the clinical effects and outcomes reported in these patients reported to the National Poison Data System (NPDS).Methods: This is a retrospective observational study of acute unintentional lithium ingestions in children <6 years of age. The primary intent of the study was to characterize acute unintentional exposures to lithium in children in this age group. As a secondary outcome, we sought to identify a weight-based threshold to empirically refer patients into a healthcare facility for symptoms consistent with moderate effect or worse. The American Association of Poison Control Centers’ NPDS was queried for all acute ingestions of lithium salts in children <6 years of age from 2000 to 2018. Inclusion criteria were single substance ingestions, unintentional-general exposure (i.e., exploratory ingestion), and followed to a known outcome or coded as potentially toxic exposure unable to follow and the patient was experiencing symptoms.Results: A total of 3045 single-substance exploratory ingestions of lithium were reported to poison centers that showed a decrease over time, consistent with decreasing use of lithium and decreasing calls to poison centers. Of the 3045 cases, we excluded 1178 leaving 1863 cases for analysis. Median age was 2 years (IQR: 1.5, 2) with 51% male cases. Management site was primarily non-health care facility (n = 808; 43.4%) with 569 (30.5%) already in a healthcare facility (HCF) when the Poison Control Center (PCC) was called and 477 (25.6%) referred to a HCF. The route of exposure was most commonly ingestion (n = 1853; 99.5%) and site of exposure was primarily home (1743; 93.6%). Medical outcomes were predominantly no effect and minor effect. There were 262 related clinical effects were reported in 184 patients (10%). The most frequently reported were vomiting (n = 76), drowsiness/lethargy (n = 58), other (n = 22), and ataxia (n = 20). Clinical effects lasted ≤2 h for 65 (33%), 2-8 h for 57 (28.9%), 8-24 h for 51 (25.9%), 1–3 days for 11 (5.6%), and >3 days to ≤1 week for 1 (0.5%); no cases resulted in clinical effects thought to be permanent and no deaths were reported. There were 1173 treatments provided to 857 patients. The most common treatments were basic and are readily performed at home; dilution (n = 492) and food/snack (n = 180). A smaller subset of patients received care that could likely only be provided in a healthcare facility including IV fluids (n = 173), other (n = 120), whole bowel irrigation (n = 46), single dose activated charcoal (n = 41), syrup of ipecac (n = 34), and lavage (n = 31). No patients received hemodialysis. A total of 425 of the exposures were referred to a healthcare facility by the PCC which had a dose coded. There was no difference in dose that resulted to referral to a healthcare facility over time (p = 0.2747). Due to the small number of moderate/major effect cases with dose information, we were unable to identify a dose-based threshold for referral to HCF.Conclusions: Severe outcomes after unintentional ingestion of lithium in pediatric patients are rare. It is likely that most asymptomatic pediatric patients <6 years do not need to be referred to the hospital after ingestion of lithium.

Analysis of 207,543 children with acute opioid poisonings from the United States National Poison Data System

Introduction: Previous studies using administrative data have demonstrated that the United States opioid epidemic is harming both adults and children, and is straining health care systems. Our objective is to describe the outcomes and trends in resource use among children with acute opioid ingestions using patient-level case report data.Materials and Methods: This study was a retrospective analysis of prospectively collected data from the 55 poison control centers in the United States which comprise the National Poison Data System (NPDS). Children under 19 years of age with a primary opioid ingestion between 1 January 2005 and 31 December 2018 were included in the analysis. Trends over three eras (2005–2009, 2010–2014, 2015–2018) were assessed using a Cochran-Armitage Trend Test. Yearly trends in the proportion of cases were calculated using generalized linear models. Multi-variable logistic regression analysis was used to calculate the adjusted odds of variables associated with having at least one Pediatric Intensive Care Unit (PICU) level intervention.Results: Children were involved in 207,543 (27.54%) of a total of 1,002,947 primary exposure-related opioid poisoning cases reported to US poison centers. The percentage of patients admitted to a critical care unit from these exposures increased in each era (6.6%, 8.5%, 9.6%). Suicidal intent increased in each era (14.0%, 15.3%, 21.2%), and was associated with increased adjusted odds of receiving a PICU procedure (OR 9.68, CI 7.97–11.76). Fentanyl (OR 12, CI 9.2–15.7), heroin (OR 11.1, CI 9.4–13.1), and methadone (OR 15, CI 13–17.3) were the opioids most associated with having a PICU procedure.Discussion and Conclusions: The severity of admissions for acute opioid ingestions, especially following attempted suicide, has increased over the studied time frame. Efforts focused on reducing access, especially to synthetic and illicit opioids, and addressing adolescent suicidality are needed to reduce these serious consequences of the opioid epidemic on children in the United States.

Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand.

Paracetamol is a common agent taken in deliberate self-poisoning and in accidental overdose in adults and children. Paracetamol poisoning is the commonest cause of severe acute liver injury. Since the publication of the previous guidelines in 2015, several studies have changed practice. A working group of experts in the area, with representation from all Poisons Information Centres of Australia and New Zealand, were brought together to produce an updated evidence-based guidance. The optimal management of most patients with paracetamol overdose is usually straightforward. Patients who present early should be given activated charcoal. Patients at risk of hepatotoxicity should receive intravenous acetylcysteine. The paracetamol nomogram is used to assess the need for treatment in acute immediate release paracetamol ingestions with a known time of ingestion. Cases that require different management include modified release paracetamol overdoses, large or massive overdoses, accidental liquid ingestion in children, and repeated supratherapeutic ingestions. The new guidelines recommend a two-bag acetylcysteine infusion regimen (200mg/kg over 4h, then 100mg/kg over 16h). This has similar efficacy but significantly reduced adverse reactions compared with the previous three-bag regimen. Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine. All potentially toxic modified release paracetamol ingestions (≥10g or ≥200mg/kg, whichever is less) should receive a full course of acetylcysteine. Patients ingesting ≥30g or ≥500mg/kg should receive increased doses of acetylcysteine.

Early acetaminophen-protein adducts predict hepatotoxicity following overdose (ATOM-5)

Acetaminophen-protein adducts are specific biomarkers of toxic acetaminophen (paracetamol) metabolite exposure. In patients with hepatotoxicity (alanine aminotransferase [ALT] >1,000 U/L), an adduct concentration ≥1.0 nmol/ml is sensitive and specific for identifying cases secondary to acetaminophen. Our aim was to characterise acetaminophen-protein adduct concentrations in patients following acetaminophen overdose and determine if they predict toxicity. We performed a multicentre prospective observational study, recruiting patients 14 years of age or older with acetaminophen overdose regardless of intent or formulation. Three serum samples were obtained within the first 24 h of presentation and analysed for acetaminophen-protein adducts. Acetaminophen-protein adduct concentrations were compared to ALT and other indicators of toxicity. Of the 240 patients who participated, 204 (85%) presented following acute ingestions, with a median ingested dose of 20 g (IQR 10-40), and 228 (95%) were treated with intravenous acetylcysteine at a median time of 6 h (IQR 3.5-10.5) post-ingestion. Thirty-six (15%) patients developed hepatotoxicity, of whom 22 had an ALT ≤1,000 U/L at the time of initial acetaminophen-protein adduct measurement. Those who developed hepatotoxicity had a higher initial acetaminophen-protein adduct concentration compared to those who did not, 1.63 nmol/ml (IQR 0.76-2.02, n= 22) vs. 0.26 nmol/ml (IQR 0.15-0.41; n= 204; p <0.0001), respectively. The AUROC for hepatotoxicity was 0.98 (95% CI 0.96-1.00; n= 226; p <0.0001) with acetaminophen-protein adduct concentration and 0.89 (95% CI 0.82-0.96; n= 219; p <0.0001) with ALT. An acetaminophen-protein adduct concentration of 0.58 nmol/ml was 100% sensitive and 91% specific for identifying patients with an initial ALT ≤1,000 U/L who would develop hepatotoxicity. Adding acetaminophen-protein adduct concentrations to risk prediction models improved prediction of hepatotoxicity to a level similar to that obtained by more complex models. Acetaminophen-protein adduct concentration on presentation predicted which patients with acetaminophen overdose subsequently developed hepatotoxicity, regardless of time of ingestion. An adduct threshold of 0.58 nmol/L was required for optimal prediction. Acetaminophen poisoning is one of the most common causes of liver injury. This study examined a new biomarker of acetaminophen toxicity, which measures the amount of toxic metabolite exposure called acetaminophen-protein adduct. We found that those who developed liver injury had a higher initial level of acetaminophen-protein adducts than those who did not. Australian Toxicology Monitoring (ATOM) Study-Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.

Polyethylene glycol electrolyte lavage solution increases tablet dissolution of acetaminophen in an in vitro model mimicking acute poisoning

IntroductionPolyethylene glycol electrolyte lavage solution (PEG-ELS) is similar to pharmaceutical solvent propylene glycol and used following acute poisonings for whole bowel irrigation (e.g., “body stuffing”). This raises concern of PEG-ELS increasing solubility following acute ingestions of non-sustained release xenobiotics in the stomach. We theorized PEG-ELS increases solubility of acetaminophen in an in vitro stomach model. Material and methodsAn in vitro artificial stomach with 500 mL simulated gastric fluid and either 500 mL of sodium chloride 0.9% (group A) or 500 mL of PEG-ELS (group B). Ten non-sustained release acetaminophen tablets added with concentrations 0, 15, 45 and 90 min in triplicate. Mean concentrations and mean area under the curve (AUC) (mg-min/L to 90 min). ResultsIn control group A (normal saline + simulated gastric fluid) mean acetaminophen concentrations 0, 3, 13 and 36 mg/L at 0, 15, 45 and 90 min, respectively. In group B (PEG-ELS + simulated gastric fluid) mean acetaminophen concentrations 0, 34, 109 and 136 mg/L at 0, 15, 45 and 90 min, respectively (p < 0.05). Mean AUC 0-90 1385 [95% C.I. 990.5–1779] mg-min/L in control group A compared to mean AUC 0-90 in group B (PEG-ELS) 7673 mg-min/L [95% C.I. 4832–10513] (p < 0.05). DiscussionGroup B (PEG-ELS) with significantly higher mean acetaminophen concentrations and greater mean AUC compared to control group A (normal saline). ConclusionWe demonstrated increased mean acetaminophen concentrations and increased mean AUC of following exposure of PEG-ELS in an artificial stomach model.

Prospective evaluation of a clinical decision tool to reduce childhood admissions to PICUs for poisoning: ReCAP2

Aim: To prospectively validate a pediatric clinical prediction model to identify children at low risk of clinically significant ingestions to prevent unnecessary pediatric intensive care unit (PICU) admissions.Methods: Calls received by the Georgia Poison Center about children for acute ingestions between May 25, 2017 and May 17, 2018 were scored in real time using the full, age-stratified, and simplified clinical scoring tool to reduce childhood admissions to PICUs for poisoning (RECAP2). Clinically significant ingestions with a poison center recommendation of PICU admission are defined in the simple RECAP2 model as ingestion of clonidine, ethanol, an oral anti-hyperglycemic agent, or exposure to carbon monoxide, as well as the presence of symptoms occurring within 2 h for an immediate release, or 4 h for an extended release, medication exposure. Model statistics and percent reduction in PICU admissions were computed.Results: There were 886 children admitted after ingestions, of which 454 (51.2%) children were admitted to intensive care. At the time of the initial poison center call to report the ingestion, 44 cases (5%) were incomplete using the full, age-stratified model compared to the complete scoring using the simple scoring model. Seventy-two children (8.1%) required monitoring or interventions performed only in a PICU. Real-time application of the full model compared with the simple model would have reduced PICU admissions by 33.3 and 31.7%, respectively.Conclusions: The simple RECAP2 clinical scoring model is a sensitive prediction tool to identify children at very low risk for clinically significant ingestions for whom PICU admission can be avoided. Clinical implementation of the simple RECAP2 model and recommendation for admission to an inpatient unit versus PICU should be further evaluated, to reduce unnecessary PICU admissions following acute ingestions.

An 11-year retrospective review of cyproheptadine use in serotonin syndrome cases reported to the California Poison Control System.

Cyproheptadine is a serotonin and histamine antagonist that has been suggested as a treatment for serotonin syndrome in case reports. We sought to examine the differences between outcomes and treatment recommendations in patients who received and did not receive cyproheptadine for a probable serotonin syndrome. A retrospective review of cases reported to the California Poison Control System between 2006 and 2017 involving cyproheptadine administration or consideration for treatment of a probable serotonin syndrome. A total of 1420 cases were identified and 288 cases met the inclusion criteria. Of these, 68 (23.1%) patients received cyproheptadine treatment and were significantly older (mean age 49.7 vs 33.5years, P<0.00001), intubated (n=35, 51% vs n=62, 28%, P<0.05) and, although not statistically significant, were more frequently admitted to a critical care unit (n=56, 82.3% vs n=154, 70.0%, P=0.09). There were no significant differences in serious outcomes (moderate or worse effects) or hospitalization rates (OR, 1.09, 95% CI, 0.49-2.64 and OR, 1.99, 95% CI, 0.86-4.58). There were eight fatalities, of which two patients received cyproheptadine. All fatalities were acute polypharmacy ingestions and had manifested severe symptoms (seizures, hypotension or hyperthermia) either prior to the administration or consideration of cyproheptadine therapy. Cyproheptadine was not administered in 138 (48%) cases primarily due to minimal clinical severity and patient improvement (43%), and not recommended in 82 (28%) cases for reasons from waiting for response to other supportive measures (30%), limited evidence of efficacy (28%) and undetermined diagnosis (14.6%). The benefits of and indications for cyproheptadine are uncertain and questionable for the management of a serotonin syndrome. Future recommendations on its use should be based on diagnostic criteria, severity of symptoms and management in conjunction with other supportive measures.

Acute bone marrow suppression and gastrointestinal toxicity following acute oral methotrexate overdose

Objective: Acute methotrexate overdose rarely causes systemic toxicity due to saturable absorption and rapid renal elimination. We present a case of methotrexate toxicity following acute overdose.Case Report: A 56-year-old female presented soon after an overdose of 1250 mg of methotrexate, zopiclone and tramadol. The methotrexate was initially under-reported (500 mg) and folinic acid was not provided. Despite normal renal function, the patient developed toxicity. She represented 5 days following the overdose with mucositis, bone marrow suppression and prolonged febrile neutropenia. Treatment included folinic acid, broad-spectrum antibiotics, filgrastim, red cell and platelet transfusion. Her bone marrow began to recover 12 days following the overdose. She was discharged home on Day 17.Discussion: Severe toxicity following an acute ingestion of a large amount of methotrexate is rarely reported. The development of toxicity was unexpected in this case given methotrexate’s pharmacokinetics and the patient’s normal renal function. The serum methotrexate concentrations were below the treatment threshold of the folinic acid rescue therapy nomogram suggesting that the nomogram should not be relied on in acute ingestions. Large acute oral methotrexate poisoning can result in systemic toxicity and folinic acid therapy should be provided in ingestions >1000 mg.