Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

A national analysis of ED presentations for early pregnancy and complications: Implications for post-Roe America.

BACKGROUND: Most obstetric emergencies are initially managed in the emergency department (ED). The Supreme Court decision of Dobbs v. Jackson Women's Health Organization, overturning Roe v. Wade, in June 2022, eliminated constitutional protection of abortion rights, allowing states to swiftly enact laws that can greatly change reproductive medicine. In this post-Roe landscape, the ambiguity and uncertainty being imposed on clinicians regarding the legality of certain interventions may have catastrophic effects. To understand and plan for the changes that will come and attempt to mitigate adverse outcomes, the authors first assessed the current state of pregnancy-related complication care in the ED setting. This study utilized data obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) to evaluate trends in pregnancy-related ED visits from 2016 to 2020 that could be impacted by restricted abortion access and trigger laws. The authors subsequently analyzed the legislative changes and translated the pertinent ones to dispel misunderstandings and provide a framework for appropriate medical practice. METHODS: The retrospective study utilized data from the NHAMCS database from 2016 to 2020, encompassing an estimated total of 4,556,778 pregnancy-related ED visits. NHAMCS is a multi-stage probabilistic sample collected by the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention (CDC) using an annual survey of EDs in the United States. All data were summarized using descriptive statistics such as proportions and 95% confidence intervals Furthermore, the supreme court decision was analyzed in addition to multiple state laws and legal texts. The findings were summarized and discussed. RESULTS: The majority (79.4%) of all studied visits were for patients between the ages of 18-34 years, capturing those in peak reproductive years. This age group also comprised of the bulk (76.4%) of visits for pathologic pregnancies, including ectopic and molar pregnancies, and 79.8% of visits for a spontaneous miscarriage or threatened miscarriage in early pregnancy. Black patients accounted for 25.7%, white patients 70.1%. Regarding ethnicity, patients were separated into Hispanic and non-Hispanic, with Hispanic patients comprising 27% of all ED visits for included diagnoses between 2016 and 2020. Most visits for complications following an induced abortion occurred in the south (70.8%) and were nearly twice as likely to occur in non-metropolitan areas. Approximately 18% patients presenting with a pathologic pregnancy required admission to the hospital and approximately 50% of those visits for pathologic pregnancies and visits for bleeding in pregnancy had a procedure in the ED (49.8% and 49.5%). There were 111,264 estimated visits in which methotrexate was administered, amounting to approximately 1 in 7 visits for ectopic or molar pregnancy. In this data set, approximately 14,000 miscarriage and early bleeding patients received misoprostol. CONCLUSION: Pregnancy-related ED visits comprise of a significant proportion of emergency care. As it relates to many of the trends previously elucidated on, the true extent of the burden cannot be predicted. It must be emphasized that contrary to popular belief, Dobbs v. Jackson does not prohibit termination of pregnancy in the setting of life-threatening conditions to the mother, including ectopic pregnancy, preeclampsia, and others, but the resultant uncertainty and ambiguity surrounding the constitutional change is leading to an over-compliance of the law, necessarily obstructing reproductive health care. The authors recommend that physicians be mindful of the rapidly-evolving laws in their particular state, and to also practice in accordance with Emergency Medical Treatment and Active Labor Act (EMTALA). Patient safety must be prioritized.

Opioid Overdose Deaths with Buprenorphine Detected in Postmortem Toxicology: a Retrospective Analysis.

BACKGROUND: Buprenorphine is a unique µ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.

Opioid Prescriptions by Specialty in Ohio, 2010-2014.

Background: The current US opioid epidemic is attributed to the large volume of prescribed opioids. This study analyzed the contribution of different medical specialties to overall opioids by evaluating the pill counts and morphine milligram equivalents (MMEs) of opioid prescriptions, stratified by provider specialty, and determined temporal trends. Methods: This was an analysis of the Ohio prescription drug monitoring program database, which captures scheduled medication prescriptions filled in the state as well as prescriber specialty. We extracted prescriptions for pill versions of opioids written in the calendar years 2010 to 2014. The main outcomes were the number of filled prescriptions, pill counts, MMEs, and extended-released opioids written by physicians in each specialty, and annual prescribing trends. Results: There were 56,873,719 prescriptions for the studied opioids dispensed, for which 41,959,581 (73.8%) had prescriber specialty type available. Mean number of pills per prescription and MMEs were highest for physical medicine/rehabilitation (PM&R; 91.2 pills, 1,532 mg, N = 1,680,579), anesthesiology/pain (89.3 pills, 1,484 mg, N = 3,261,449), hematology/oncology (88.2 pills, 1,534 mg, N = 516,596), and neurology (84.4 pills, 1,230 mg, N = 573,389). Family medicine (21.8%) and internal medicine (17.6%) wrote the most opioid prescriptions overall. Time trends in the average number of pills and MMEs per prescription also varied depending on specialty. Conclusions: The numbers of pills and MMEs per opioid prescription vary markedly by prescriber specialty, as do trends in prescribing characteristics. Pill count and MME values define each specialty's contribution to overall opioid prescribing more accurately than the number of prescriptions alone.

Something for pain: Responsible opioid use in emergency medicine.

The United States is currently experiencing a public health crisis of opioid addiction, which has its genesis in an industry marketing effort that successfully encouraged clinicians to prescribe opioids liberally, and asserted the safety of prescribing opioids for chronic non-cancer pain, despite a preponderance of evidence demonstrating the risks of dependence and misuse. The resulting rise in opioid use has pushed drug overdose deaths in front of motor vehicle collisions to become the leading cause of accidental death in the country. Emergency providers frequently treat patients for complications of opioid abuse, and also manage patients with acute and chronic pain, for which opioids are routinely prescribed. Emergency providers are therefore well positioned to both prevent new cases of opioid misuse and initiate appropriate treatment of existing opioid addicts. In opioid-naive patients, this is accomplished by a careful consideration of the likelihood of benefit and harm of an opioid prescription for acute pain. If opioids are prescribed, the chance of harm is reduced by matching the number of pills prescribed to the expected duration of pain and selecting an opioid preparation with low abuse liability. Patients who present to acute care with exacerbations of chronic pain or painful conditions associated with opioid misuse are best managed by treating symptoms with opioid alternatives and encouraging treatment for opioid addiction.

Opioid Prescribing in a Cross Section of US Emergency Departments.

STUDY OBJECTIVE: Opioid pain reliever prescribing at emergency department (ED) discharge has increased in the past decade but specific prescription details are lacking. Previous ED opioid pain reliever prescribing estimates relied on national survey extrapolation or prescription databases. The main goal of this study is to use a research consortium to analyze the characteristics of patients and opioid prescriptions, using a national sample of ED patients. We also aim to examine the indications for opioid pain reliever prescribing, characteristics of opioids prescribed both in the ED and at discharge, and characteristics of patients who received opioid pain relievers compared with those who did not. METHODS: This observational, multicenter, retrospective, cohort study assessed opioid pain reliever prescribing to consecutive patients presenting to the consortium EDs during 1 week in October 2012. The consortium study sites consisted of 19 EDs representing 1.4 million annual visits, varied geographically, and were predominantly academic centers. Medical records of all patients aged 18 to 90 years and discharged with an opioid pain reliever (excluding tramadol) were individually abstracted by standardized chart review by investigators for detailed analysis. Descriptive statistics were generated. RESULTS: During the study week, 27,516 patient visits were evaluated in the consortium EDs; 19,321 patients (70.2%) were discharged and 3,284 (11.9% of all patients and 17.0% of discharged patients) received an opioid pain reliever prescription. For patients prescribed an opioid pain reliever, mean age was 41 years (SD 14 years) and 1,694 (51.6%) were women. Mean initial pain score was 7.7 (SD 2.4). The most common diagnoses associated with opioid pain reliever prescribing were back pain (10.2%), abdominal pain (10.1%), and extremity fracture (7.1%) or sprain (6.5%). The most common opioid pain relievers prescribed were oxycodone (52.3%), hydrocodone (40.9%), and codeine (4.8%). Greater than 99% of pain relievers were immediate release and 90.0% were combination preparations, and the mean and median number of pills was 16.6 (SD 7.6) and 15 (interquartile range 12 to 20), respectively. CONCLUSION: In a study of ED patients treated during a single week across the country, 17% of discharged patients were prescribed opioid pain relievers. The majority of the prescriptions had small pill counts and almost exclusively immediate-release formulations.

Methotrexate toxicity treated with continuous venovenous hemofiltration, leucovorin and glucarpidase.

High-dose methotrexate (MTX) can produce acute kidney injury, impairing MTX elimination. Continuous venovenous hemofiltration (CVVH) may enhance elimination in this setting, although its use is largely unstudied. A 79-year-old man received IV MTX for central nervous system lymphoma, and over a 34-h period his serum creatinine increased from 1.09 to 2.24 mg/dL. His serum MTX concentration (sMTX) at the end of this time period was 59.05 µmol/L. After urinary alkalinization and leucovorin and glucarpidase (CPDG2) treatment, sMTX decreased. Fluid overload ensued and CVVH was initiated. The initial MTX extraction ratio and clearance were 0.22 and 47.0 mL/min, respectively. No MTX extraction occurred at an sMTX of 0.15 µmol/L. Continuous venovenous hemodialysis was initiated, and sMTX further declined. CVVH may help eliminate MTX and provide renal replacement at moderate sMTX.

A case of near-fatal flecainide overdose in a neonate successfully treated with sodium bicarbonate.

BACKGROUND: Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate. CASE REPORT: An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high heart rates (220-240 beats/min) and electrocardiographic changes consistent with SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a transthoracic echocardiogram showed no underlying structural abnormality. The patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40 beats/min with no palpable pulse. The patient was given 0.1 mg of atropine intravenously, with an increase of the heart rate to 160 beats/min. The child's cardiac monitor revealed a wide-complex tachycardia with left bundle branch morphology, with associated pallor and poor capillary refill. Sodium bicarbonate was administered intravenously due to suspected flecainide toxicity. Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum flecainide concentration was 1360 µg/L (therapeutic, 200-1000 µg/L) drawn 1 h before the cardiac arrest. It was later discovered that a twofold dosing error occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses. CONCLUSION: Flecainide toxicity in children is rare, especially in neonates. It is important for clinicians to be able to identify and treat this uncommon poisoning.

Fatal aluminum phosphide poisoning in Tehran-Iran from 2007 to 2010.

BACKGROUND: Aluminum phosphide (AlP) is also known as "rice tablet" in Iran. Due to the high incidence of acute AlP poisoning and its associated mortality in Iran, the authorities banned AlP-containing tablets in 2007. The aim of this study is to evaluate the trend of acute fatal AlP poisoning subsequent to this restriction. MATERIALS AND METHODS: 0 This is a retrospective chart review of patients with acute "rice tablet" poisoning who were admitted to Loghman Hakim Hospital Poison Center, Tehran, Iran, from 2007 to 2010. Collected information included gender, age, type of poisoning, marital status, duration of hospitalization, and outcome. RESULTS: There were 956 cases with a mortality rate of 24.06%. The incidence of fatal AlP poisoning was 2.1 and 5.81 per one million populations of Tehran in 2007 and 2010, respectively. In 223 of the fatal cases (97%) and 697 of the non-fatal cases (96%), the poisoning was intentional. The male to female ratio in the fatal and non-fatal cases was 1.04:1 and 1:1.3, respectively. Most of the fatal cases (n = 122, 53%) were unmarried. The mean age was 27.32 ± 11.31 and 24.5 ± 8.19 years in fatal and non-fatal cases, respectively. In 196 (85.2%) of the fatal cases and in 577 (79%) of non-fatal cases, the duration of hospitalization was less than 24 hours and between 48-72 hours, respectively. CONCLUSION: The results of this study showed the incidence of "rice tablet" poisoning, and its mortality increased since 2007 in spite of the ban. It seems that legislative means alone without other interventions, such as suicide prevention and public education, will not always be able to control or prevent acute intentional poisonings.

Life-threatening bupropion ingestion: is there a role for intravenous fat emulsion?

Intravenous fat emulsion (IFE) is emerging as a novel antidote in clinical toxicology. Its current usage is extending beyond local anaesthetic toxicity into management of severe toxicity from some lipophilic drugs. We present a 51-year-old woman with severe bupropion toxicity whose haemodynamic status transiently improved after IFE. Serum analysis demonstrated an increase in serum concentration of hydroxybupropion, an active metabolite of bupropion, after IFE administration, lending support to one of the proposed mechanisms of IFE. A 51-year-old woman presented to the emergency department with generalised tonic-clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium bicarbonate therapy, the patient developed profound hypotension refractory to high-dose norepinephrine. IFE was administered with haemodynamic improvement over the course of 30 min., followed by a significant decrease in norepinephrine requirement. The patient had an episode of ventricular tachycardia 24 hr after presentation, and received a second infusion of IFE. Analysis of serum for a panel of myocardial sodium channel blocking drugs revealed that significant bupropion ingestion had occurred. Bupropion poisoning may produce life-threatening clinical effects, and IFE may be considered in cases of severe haemodynamic instability. Further studies would be instrumental in determining the optimal clinical situations for utilisation of IFE.

Attempted suicide, by mail order: Abrus precatorius.

OBJECTIVE: Abrus precatorius is cultivated in many subtropical areas. The seeds exist in a variety of colors such as black, orange, and most commonly, glossy red. A black band is found at the end of the seed. The plant contains multiple pods which typically contain three to five Abrus seeds. The seeds contain abrin, which inhibits ribosomal function, halting protein synthesis and leading to cellular death. A unique aspect of this case is the use of the internet to order a potentially lethal poison as well as transmission of a picture to identify the seed. CASE REPORT: A 20-year-old man presented to the emergency department complaining of vomiting and watery diarrhea for 6-8 h prior to arrival. He denied any medication use, recent illness, travel, or changes in his diet. Initial vital signs were normal. The patient was diagnosed with viral gastroenteritis. During his evaluation, the patient admitted to feeling suicidal. While awaiting psychiatry evaluation, the patient's father arrived with a box of small hard red seeds, which he believed that his son ingested in a suicide attempt. The seeds could not be identified by the staff. A picture of the seeds was transmitted by e-mail to the New York City Poison Control Center, allowing their identification as A. precatorius. The patient was reinterviewed and admitted to chewing and swallowing 10 seeds. Given the potential toxicity of abrin, the patient was admitted to the intensive care unit. He continued to have frequent episodes of emesis as well as diarrhea. He gradually improved over 2 days. He admitted to ordering a box of Abrus seeds online from Asia after reading on the Internet about their use in suicide. He was eventually discharged for outpatient follow-up with no permanent sequelae. CONCLUSION: Abrin has an estimated human fatal dose of 0.1-1 µg/kg. Most cases of Abrus seed ingestions are unintentional and occur in children. Ingesting the intact seeds typically results in no clinical findings, as they pass through the gastrointestinal tract due to their hard shell. Abrin released during chewing is poorly absorbed systemically from the gastrointestinal tract. This causes the vomiting and diarrhea with resultant hypovolemia and electrolyte disturbances, which can be severe and life threatening, particularly in areas with less advanced health care systems. Management is primarily supportive.

Relationship between serum glycolate and falsely elevated lactate in severe ethylene glycol poisoning.

In the setting of ethylene glycol (EG) poisoning, a falsely elevated serum lactate concentration is suggested to be an assay cross-reaction with glycolate, but a concentration-dependent relationship has never been identified. We correlate serum lactate and glycolate concentrations in a case of severe EG poisoning. Serial EG [by gas chromatography (GC)], glycolate (derivatized to methyl glycolate, analysis by GC), and lactate (both enzymatic spectrophotometry and GC) concentrations were correlated at five time points. False-positive lactate was confirmed by absence of lactate on GC analysis. The correlation coefficient (Pearson's r) between lactate (by enzymatic spectrophotometry) and glycolate was 0.984 and was statistically significant (p < 0.01). The mean lactate/glycolate conversion factor was 2.58 +/- 0.95. We demonstrate the linear correlation between falsely elevated serum lactate and glycolate concentrations in a case of severe EG poisoning. Our data provide further support to the belief that the lactate assay may cross-react with glycolate in EG poisoning.

Multisystem organ failure after large volume injection of castor oil.

We report a case of multisystem organ failure after large volume subcutaneous injection of castor oil for cosmetic enhancement. An unlicensed practitioner injected 500 mL of castor oil bilaterally to the hips and buttocks of a 28-year-old male to female transsexual. Immediate local pain and erythema were followed by abdominal and chest pain, emesis, headache, hematuria, jaundice, and tinnitus. She presented to an emergency department 12 hours postinjection. Persistently hemolyzed blood samples complicated preliminary laboratory analysis. She rapidly deteriorated despite treatment and developed fever, tachycardia, hemolysis, thrombocytopenia, hepatitis, respiratory distress, and anuric renal failure. An infectious diseases evaluation was negative. After intensive supportive care, including mechanical ventilation and hemodialysis, she was discharged 11 days later, requiring dialysis for an additional 1.5 months. Castor oil absorption was inferred from recovery of the Ricinus communis biomarker, ricinine, in the patient's urine (41 ng/mL). Clinicians should anticipate multiple complications after unapproved methods of cosmetic enhancement.

A rapid qualitative test for suspected ethylene glycol poisoning.

OBJECTIVES: Many hospitals must send out ethylene glycol (EG) samples to a reference laboratory, and delays in diagnosis and treatment may occur. A qualitative colorimetric test (ethylene glycol test [EGT] kit), already in use by veterinarians, gives results in 30 minutes with little expertise or cost. The EGT reliably detects the presence of EG in spiked human serum samples. The objective of this study was to prospectively assess the sensitivity and specificity of the EGT kit in actual clinical samples submitted for EG testing by the criterion standard gas chromatography (GC). METHODS: Blood samples from patients with suspected toxic alcohol poisoning submitted to a reference laboratory were tested by GC. An investigator blinded to the GC results tested the same sample with the EGT kit following the manufacturer's instructions and using the internal control. Three physicians also blinded to the GC results categorized the sample as positive for EG, negative, or inconclusive. Interrater reliability was assessed with a kappa statistic (kappa). Results of the EGT kit testing were then compared to those from GC testing. RESULTS: Data are reported on 24 samples submitted. By GC, 15 samples were confirmed for EG (range 27-281 mg/dL), 5 were confirmed for methanol (ME; range 64-101 mg/dL), and 4 were negative for both alcohols. The EGT was unanimously positive in all confirmed EG samples and negative in all ME samples. In one of the negative samples, an ambiguous result occurred and was counted as a false-positive. Interobserver agreement with the EGT was high (kappa = 0.909; 95% confidence interval [CI] = 0.735 to 1.0). Sensitivity and specificity were 100% (95% CI = 70% to 100%) and 88.8% (95% CI = 52% to 100%), respectively. CONCLUSIONS: The EGT appears to be a reliable qualitative test in cases of suspected human EG poisoning.