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.

Poison control center experience with tianeptine: an unregulated pharmaceutical product with potential for abuse.

Background: Interest in tianeptine as a potential drug of abuse is increasing in the United States. We performed a retrospective study of calls to the New York State Poison Control Centers (PCCs) designed to characterize one state's experience with tianeptine. Methods: Data were gathered from existing records utilizing the poison center data collection system, Toxicall® entered between 1 January 2000 through 1 April 2017. Information regarding patient demographics, reported dose and formulation of tianeptine, reported coingestants, brief narrative description of the case, disposition, and case outcome was collected. Results: There were nine reported cases of tianeptine exposure. Seven were male with a mean age of 27. Three reported therapeutic use of tianeptine and five reported intentional abuse. One case was an unintentional pediatric exposure. Doses were reported in three cases; 12.5 mg in a pediatric unintentional exposure, and 5 and 10 g daily in the two reports of intentional abuse. Of note, five patients complained of symptoms consistent with opioid withdrawal. In one of two cases in which naloxone was administered, an improvement in mental status and the respiratory drive was noted. Outcomes reported in Toxicall® were minor in two cases, moderate in five cases, major in one case, and not reported in one case. Conclusions: These cases, reported to the New York State PCCs should alert readers to the potential for tianeptine abuse, dependence, and withdrawal.

Notes from the Field: Cardiac Dysrhythmias After Loperamide Abuse - New York, 2008-2016.

Loperamide is an over-the-counter antidiarrheal with opioid-receptor agonist properties. Recommended over-the-counter doses (range = 2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for self-treatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.

Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

BACKGROUND: Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. METHODS: Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. RESULTS: For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence. CONCLUSION: Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity.

BACKGROUND: The use of intravenous lipid emulsion (ILE) therapy for the treatment of lipophilic drug toxicity is increasing. Despite this, the evidence for its effect in non-local anesthetic toxicity remains sparse. Furthermore, many case reports describe ILE use for substances in which no clear efficacy data exists. The American Academy of Clinical Toxicology established a lipid emulsion workgroup. The aim of this group is to review the available evidence regarding the effect of ILE in non-LA drug poisoning and develop consensus-based recommendations on the use of this therapy. METHODS: A systematic review of the literature was performed to capture articles through 15 December 2014. Relevant articles were determined based upon a predefined methodology. Articles involving pre-treatment experiments, pharmacokinetic studies not involving toxicity, and studies not addressing antidotal use of ILE met pre-defined exclusion criteria. Agreement of at least two members of the subgroup was required before an article could be excluded. RESULTS: The final analysis included 203 articles: 141 for humans and 62 for animals. These include 40 animal experiments and 22 case reports involving animal toxicity. There were three human randomized control trials (RCT): one RCT examined ILE in TCA overdose, one RCT examined ILE in various overdoses, and one study examined ILE in reversal of sedation after therapeutic administration of inhaled anesthesia. One observational study examined ILE in glyphosate overdose. In addition, 137 human case reports or case series were identified. Intravenous lipid emulsion therapy was used in the management of overdose with 65 unique substances. CONCLUSIONS: Despite the use of ILE for multiple substances in the treatment of patients with poisoning and overdose, the effect of ILE in various non-local anesthetic poisonings is heterogenous, and the quality of evidence remains low to very low.

Sodium channel blockade with QRS widening after an escitalopram overdose.

INTRODUCTION: Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose. CASE: A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen. Laboratory results were significant for 4-hour acetaminophen 21.1 µg/mL. Serum electrolytes including potassium, magnesium, and calcium were all normal. Initial electrocardiogram (ECG) revealed a widened QRS with an incomplete right bundle branch pattern. After administration of 100-mEq sodium bicarbonate, a repeat ECG revealed narrowing of the QRS complex and a prolonged QTc interval. Magnesium sulfate 2 g intravenous and sodium bicarbonate drip were initiated. A repeat ECG, 1 hour after the second, revealed normalization of the QRS complex and QTc interval. DISCUSSION: Prolongation of the QTc interval is an expected effect of escitalopram. Both escitalopram and citalopram are metabolized to the cardiotoxic metabolite S-didesmethylcitalopram and didesmethylcitalopram, respectively, which have been implicated in numerous cardiac abnormalities including widening of the QRS complex. Although never previously described with escitalopram, this mechanism provides a reasonable explanation for the QRS complex widening and incomplete right bundle branch block that occurred in our patient. CONCLUSIONS: Both QRS complex widening and QTc interval prolongation should be monitored in cases of escitalopram and citalopram overdoses.

Elevated International Normalized Ratio associated with long-term azithromycin therapy in a child with cerebral palsy.

PURPOSE: A case of coagulopathy in a pre-adolescent with cerebral palsy that developed after chronic prophylactic antibiotic use is reported. SUMMARY: An 11-year-old boy with cerebral palsy was brought to the emergency department experiencing restlessness and decreased oxygen saturation. Evaluation of the patient revealed gallstone-related pancreatitis, with elevated serum amylase and lipase concentrations and abnormal liver function test results. At the time of the initial evaluation, the International Normalized Ratio (INR) was 6.54 (normal range, 0.8-1.2), and the activated partial thromboplastin time was 53.8 seconds (normal range, 24.4-34.8 seconds). The boy's medication history included use of azithromycin 200 mg every other day for about two years for antiinflammatory therapy. On confirmation of the elevated INR 2 hours after the initial evaluation, azithromycin was discontinued, and a single dose of phytonadione 2 mg was administered. About 14 hours after phytonadione administration, the INR had declined to 0.94; 43 hours later, the INR remained within the normal range without further phytonadione therapy. Using the probability scale of Naranjo and colleagues, this case was rated as a probable drug-related adverse event. Previous reports have linked the development of vitamin K deficiency and impaired coagulation to long-term antibiotic use, but not specifically to use of azithromycin or other macrolide antibiotics. CONCLUSION: An elevated INR in a child with cerebral palsy was evidently related to long-term therapy with azithromycin. The abnormal INR normalized after discontinuation of azithromycin and administration of one dose of phytonadione.

Diethylene glycol: widely used solvent presents serious poisoning potential.

OBJECTIVE: To describe the serious toxicity of a readily available solvent, diethylene glycol (DEG). We describe a case of intentional ingestion of a wallpaper stripper containing DEG resulting in severe multi-system organ failure. CASE REPORT: A 27-year-old male presented to the Emergency Department (ED) one day after ingesting wallpaper stripper containing DEG. He developed acidosis, renal cortical necrosis, hepatocellular injury, and severe neurologic sequelae, including cranial neuropathies and peripheral demyelinating sensori-motor polyneuropathy. His neurologic function improved over 5 months. DISCUSSION: Our case demonstrates the severe toxicity of DEG. DEG is present in numerous formulations, often without proper protective packaging. DEG has been associated with severe epidemic poisonings in the past and with the availability of safer alternatives, DEG in consumer products should be eliminated. CONCLUSION: DEG is found in numerous products. Delays in treatment can have devastating results, resulting in death or permanent disability. The pervasive use of this compound makes further human exposures likely.

Profound metabolic acidosis and oxoprolinuria in an adult.

INTRODUCTION: Profound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation. CASE REPORT: A 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was only modestly elevated. There was no evidence of ketoacids, salicylate, methanol, or ethylene glycol. A urine sample submitted on day 1 of hospitalization revealed a markedly elevated level of 5-oxoproline. DISCUSSION: Originally described in children with an inherited defect of glutathione synthetase, 5-oxoproline is an unusual cause of metabolic acidosis. More recently this disturbance has been recognized in critically ill adults without a recognized inherited metabolic disorder. In most of these cases there has been the concomitant use of acetaminophen. Any causal relationship between acetaminophen and this disturbance is speculative. CONCLUSION: In critically ill adults with unexplained metabolic acidosis, 5-Oxoproline should be considered in the differential.

The use of vasopressin in the setting of recalcitrant hypotension due to calcium channel blocker overdose.

Treatment of hypotension caused by calcium channel blocker overdose (CCB) remains a challenge. We describe the successful use of vasopressin in two patients with massive CCB overdoses in whom hypotension was unresponsive to calcium, glucagon, insulin, and conventional vasopressor therapies. While various modes of treatments have been used to treat the hypotension of CCB overdose, this is the first report to our knowledge of the successful use of vasopressin in this clinical setting.

Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

OBJECTIVES: To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. METHODS: This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p < 0.05 considered significant. RESULTS: A total of 166 subjects were enrolled; data for analysis were available for 44 NS-treated patients, 46 ondansetron-treated patients, and 47 dexamethasone-treated patients. Hospital admission occurred in nine patients (20.5%) receiving placebo (NS alone), two patients (4.4%) receiving ondansetron, and seven patients (14.9%) receiving dexamethasone, with ondansetron significantly different from placebo (p = 0.02). Similarly, at two hours, more ondansetron-treated patients (39 [86.6%]) tolerated oral hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. CONCLUSIONS: In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

Hospital pharmacology: An alternative model for practice and training in clinical pharmacology.

External pressures continue to be exerted on hospitals to prioritize programs that minimize costs and improve the safety of medication use. Clinical pharmacologists are in an ideal position to provide leadership for such programs. At academic health centers, an added dimension is the exposure of physicians-in-training to the practical application of clinical pharmacology principles. At SUNY Upstate Medical University, the approach is led by a physician with clinical pharmacists and pharmacy practice residents. To align the clinical pharmacists with the overall goals of the program, a faculty promotions track system designed specifically for them has been enacted within the college of medicine. This report summarizes the "hospital pharmacology" program that provides funding for an academic physician-clinical pharmacologist. With this report, the authors hope to outline an alternative practice and training paradigm to potentially address the decline in physicians being trained in and practicing clinical pharmacology since the late 1970s.

Severe hyperphosphatemia and hypocalcemia following the rectal administration of a phosphate-containing Fleet pediatric enema.

BACKGROUND: Toxicity secondary to rectally administered hypertonic phosphate solution in patients with normal renal function is rarely reported in the literature. We report a case of electrolyte disturbance and seizure secondary to the rectal administration of 2 Fleet pediatric enemas. CASE REPORT: A 4-year-old white female with spinal muscular atrophy and chronic constipation was brought to the emergency department with complaints of lethargy and difficulty breathing following the administration of 2 Fleet pediatric enemas. In the emergency department, physical examination was significant for a depressed level of consciousness and shallow respirations. A basic metabolic profile was significant for a calcium of 3.3 mg/dL, phosphate of 23 mg/dL, and sodium of 153 mEq/L. Arterial blood gases revealed a pH of 7.24, Pco2 of 38 mm Hg, Po2 of 220 mm Hg. Electrocardiogram revealed a prolonged QT interval of 340 milliseconds with a corrected QT interval of 498 milliseconds. Sixteen hours postexposure, she experienced a generalized seizure unresponsive to multiple doses of lorazepam and responsive only to 100 mg of intravenous calcium chloride. Two days after presentation, the patient experienced complete resolution of symptoms. CONCLUSION: Osmotically acting hypertonic phosphate enemas can result in severe toxicity if retained. This is true even in patients without predisposing risk factors.

A rare ingestion of the Black Locust tree.

BACKGROUND: The Black Locust (Robinia Pseudoacacia) tree contain toxalbumins, robin and phasin, that exert their toxic effects by inhibition of protein synthesis. Despite the potential dangers of Black Locust intoxication, reports of human toxicity after ingestion are rare. We report the first human intoxication of Black Locust bark in North America in over one hundred years. CASE REPORT: An eight-year-old male was brought to the emergency department 6 hours after chewing and expelling the Black Locust bark. He presented with emesis, which began approximately 2.5 hours after exposure. His vital signs were as follows: oral temperature, 97.5 degrees F; blood pressure, 128/75 mmHg; heart rate, 114 beats per minute; respiratory rate, 15 breaths per minute. Initial treatment included 4 mg i.v. ondansetron, which resolved the vomiting, one dose of activated charcoal, and intravenous fluids. He was then admitted to the intensive care unit (ICU) for observation of signs of toxicity. Laboratory findings were unremarkable except for a white blood cell of 18.4 K/uL and an elevated alkaline phosphatase of 183 U/L. The patient remained asymptomatic throughout his stay in the ICU and was discharged on the fifth day of admission with a normal white blood cell of 4.1 K/uL and an alkaline phosphatase of 251 U/L. CONCLUSION: Patients with clinical toxicity following the ingestion of Black Locust are expected to do well with supportive care and observation.

Pediatric toxicologic concerns.

Pediatric poisonings account for significant morbidity in the United States each year. Clinicians must keep current with advances in toxicology to be familiar with the latest recommended treatment regimens and antidotes. They also must be familiar in identifying toxidromes and important physical examination findings. Having these skills can enable the clinician to determine who is at risk for significant morbidity or mortality and to provide the appropriate medical care.