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.

Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning.

Introduction: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC. Methods: We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration. Results: Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC. Conclusion: For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.

Risk of peri-intubation adverse events during emergency department intubation of overdose patients: a national emergency airway registry (near) analysis.

BACKGROUND: More than 20,000 emergency department (ED) patients undergo intubation for overdose each year. While the characteristics of patients intubated for overdose and poisoning are well described, little is known about the intubation outcomes of overdose patients in the ED. OBJECTIVES: We quantify the frequency of peri-intubation adverse events for patients intubated in the ED for overdose, and determine whether first attempt success without adverse events differs between patients intubated for overdose and patients intubated for other reasons. METHODS: We analyzed data from the National Emergency Airway Registry (NEAR), a prospective multicenter registry of ED intubations collected from an international network of 22 academic and community hospitals. We included patients 14 years and older whose first attempt was oral intubation, with data entered into NEAR between 1 January 2016 and 31 December 2018. The primary outcome was successful intubation on the first attempt. We used multivariable logistic regression to determine whether indication was independently associated with successful intubation on the first attempt after adjusting for age, gender, obesity, initial impression of difficult airway, presence of difficult airway characteristics, and use of video laryngoscopy. Secondary outcomes included successful intubation on the first attempt without adverse events, the occurrence of rescue surgical airways, and the occurrence of adverse events. Adverse events included hypoxemia, hypotension, peri-intubation cardiac arrest, bradycardia, mechanical injury to oral or airway structures, vomiting, tachydysrhythmia, esophageal intubation, laryngospasm, and pneumothorax. RESULTS: We analyzed 17,984 patients, including 1,983 (11%) intubated for overdose, and 16,001 (89%) intubated for other indications. Patients intubated for overdose were younger (median age 38 vs 55 years), were less frequently obese (26% vs 34%), and fewer had difficult airway characteristics (38% vs 53%). Overdose patients were more likely to have preoxygenation performed (45% vs 35%), more likely to have apenic oxygenation (39% vs 31%), and more likely to have bougie used (33% vs 17%). First attempt success was 90.5% in patients intubated for overdose and 87.5% in patients intubated for other reasons (absolute difference 3.0%; 95% CI: -1.3 to 7.3). First attempt success without adverse events was higher in overdose patients (85.0%) compared to other patients (78.7%) (absolute difference, 6.3%; 95% CI 1.0 to 11.7%). Overdose patients experienced significantly less hypotension (1.5% vs 4.1%), and tended to have fewer adverse events overall. Multivariable model results were consistent with the unadjusted results including no difference in first pass success (adjusted odd ratio 1.02 [95% CI 0.86-1.23]). There was a higher first pass success without complication in patients intubated for overdose (adjusted odds ratio 1.23; 95% CI 1.07 to1.43). CONCLUSION: For patients in whom the primary indication for intubation is overdose there is an increased chance of first attempt success without adverse event.

Utility of plain abdominal radiography in adult ED patients with suspected constipation.

BACKGROUND: Abdominal radiographs are often obtained in ED patients with suspected constipation, although their utility in adults is not well understood. We sought to compare ED management when an abdominal radiograph is and is not obtained. METHODS: We performed a retrospective chart review study of adult ED patients with a chief complaint of constipation from 2010 through 2016. Trained abstractors recorded radiologic tests ordered, treatments received, and final diagnosis. We determined the physician interpretation of the abdominal radiograph and its use in clinical decision making. RESULTS: Of 1142 eligible patients, 481 (42%) patients underwent abdominal radiography. Stool burden rated moderate or large was observed in 271 patients (46%). Sixteen patients (3%) were diagnosed with small bowel obstruction; 15/16 of these patients had high risk features such as old age, complex surgical history, history of small bowel obstruction, abdominal malignancy, or presented with vomiting or inability to pass flatus. Of the 197 patients with no or mild stool burden or normal radiograph, 109 (55%) were diagnosed with constipation and 89 (45%) received constipation treatment in the ED. Conversely, of the 271 patients with moderate or greater stool burden, 114 (42%) received no treatment for constipation in the ED and 104 (38%) were prescribed no discharge medications for constipation; 77 of these 271 patients (28%) were diagnosed with something other than constipation. CONCLUSION: Plain abdominal radiography did not appear to significantly affect the ED management of patients presenting with constipation; it was common for patients to receive treatment that was in direct opposition to radiographic findings. Though a small number of patients had concerning diagnoses identified on plain radiography, the history and physical examination should have sufficiently excluded simple constipation, prompting an alternate diagnostic approach. Fecal loading on radiography does not preclude a more serious diagnosis. In conclusion, abdominal radiography appears to have low value in patients with constipation.

Dose-Dependent Pulmonary Injury Following Nitrogen Dioxide Inhalation From Kinepak™ Detonation.

BACKGROUND: Nitrogen dioxide (NO2) is a pulmonary irritant produced as a byproduct of bacterial anaerobic metabolism of organic materials, and is also produced as a byproduct of explosive detonations. Significant NO2 exposure results in free-radical-induced pulmonary injury that may be delayed up to 3-30 h after exposure and can progress to acute respiratory distress syndrome (ARDS) and death. Here we present a case series of 3 patients with dose-dependent pulmonary injury consistent with NO2 inhalation following exposure to fumes from detonation of an ammonium nitrate/nitromethane (ANNM) explosive device. CASE REPORTS: Three individuals presented to the emergency department over the course of 16 h, beginning approximately 16 h after exposure to fumes from an ANNM explosive device. Patient 1, with the most significant exposure, developed ARDS necessitating intubation and mechanical ventilation. Patient 2 exhibited hypoxia and findings concerning for diffuse airway inflammation, but ultimately required only supplemental oxygen. Patient 3, with the least exposure, had imaging abnormalities but required no intervention. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Respiratory distress is a common presenting complaint to the emergency department. Because of the delayed presentation and the potential for progressive worsening of symptoms associated with NO2 exposure, it is important that emergency physicians be aware of the multiple potential means of exposure and consider this diagnosis in the proper clinical context. Patients with suspicion of NO2-related lung injury should undergo more extended observation than their initial clinical presentation may suggest.

Physostigmine Reversal of Dysarthria and Delirium After Iatrogenic Atropine Overdose From a Dental Procedure.

BACKGROUND: Sublingual atropine, dosed at 0.4-0.8 mg, is used by dentists as an antisialogogue to facilitate and increase the speed of procedures. Concentrated ophthalmic atropine drops (10 mg/mL) are commonly used off-label for this purpose. These highly concentrated drops may result in medication errors, atropine toxicity, and the antimuscarinic toxidrome. We report a case of a man who suffered acute delirium and dysarthria (from dry mouth) after an iatrogenic overdose from a dental procedure. His symptoms were initially interpreted as a stroke, but they completely resolved with physostigmine. CASE REPORT: A 57-year-old man presented with acute dysarthria and delirium after a dental procedure; 4 hours earlier he was fitted for a temporary replacement of some premolar/molar teeth. He received sublingual atropine to assist in gingival drying for molding of his prosthesis, but a calculation error resulted in the administration of approximately 113 mg. A stroke evaluation was initially planned; however, 2.5 mg of intravenous physostigmine completely reversed his symptoms. His symptoms reoccurred and were successfully treated twice more with physostigmine; the patient was observed overnight with no additional symptoms and safely discharged the next morning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ophthalmic atropine drops are highly concentrated and may cause an overdose after ingestion of small amounts. This novel case highlights the importance of considering antimuscarinic poisoning in cases of acute delirium or dysarthria after dental procedures and stands as a reminder to inquire about the use of atropine drops in such cases. Timely recognition of the antimuscarinic toxidrome and appropriate use of physostigmine may prevent unnecessary testing while providing an effective therapy. This case also highlights the need for observation after resolution of delirium treated with physostigmine.

Clevidipine versus sodium nitroprusside in acute aortic dissection: A retrospective chart review.

AIM: Intravenous vasodilators are often added to beta-blocking agents to reach blood pressure (BP) goals in aortic dissection. Control of BP using clevidipine has been described in hypertensive emergencies and cardiac surgery but not in aortic dissection. The aim of this study was to compare clevidipine versus sodium nitroprusside (SNP) as adjunct agents to esmolol for BP management in aortic dissection. METHODS: A single-center retrospective chart review evaluated patients diagnosed with aortic dissection. The primary outcome measure was time to reach patient specific systolic blood pressure (SBPPT) goals after initiation of esmolol infusion. Efficacy of clevidipine and SNP was assessed using area under the curve analysis of positive and negative excursions outside of SBPPT goals (AUCSBPe). Cost data was calculated using average wholesale price in U.S. dollars. RESULTS: Fourteen patients were included in final analyses. Median systolic BP immediately prior to initiation of esmolol was 162mm Hg vs 161mm Hg for clevidipine and SNP groups, respectively (p=0.99). Median time to reach SBPPT goal was similar between clevidipine and SNP (1.68 versus 1.03h [p=0.99]). Median AUCSBPe was similar for clevidipine and SNP (206.9 versus 538.9 mm Hg∗min∗hr-1 [p=0.11]). Cost was significantly reduced using clevidipine versus SNP ($1223.28/day versus $7674.24/day [p<0.001]). CONCLUSIONS: Clevidipine administration during initial medical management of aortic dissection showed similar efficacy compared to SNP when used as adjunct therapy to esmolol. These data suggest clevidipine is a less costly, reasonable alternative to SNP in acute aortic dissection as adjunct therapy to esmolol. Further studies are needed to validate these results.

Randomized clinical trial of propofol versus alfentanil for moderate procedural sedation in the emergency department.

STUDY OBJECTIVE: To compare the frequency of airway and respiratory adverse events leading to an intervention between moderate sedation using alfentanil or propofol. METHODS: We performed a randomized clinical trial in which adults undergoing moderate sedation in the ED received either alfentanil or propofol. Our primary outcome was the frequency of airway and respiratory adverse events leading to an intervention. Other outcomes included sedation depth, efficacy, sedation time, patient satisfaction, pain, and satisfaction. RESULTS: 108 subjects completed the trial: 52 receiving alfentanil and 56 receiving propofol. Airway or respiratory adverse events leading to an intervention were similar between the two groups: 23% for alfentanil and 20% for propofol (p=0.657). There were no serious adverse events in any group. Secondary outcomes were notably different in the rate of reported pain (48% for alfentanil, 13% for propofol) and recall (75% for alfentanil, 23% for propofol) and similar in the rate of satisfaction with the procedure (87% for alfentanil, 84% for propofol). CONCLUSION: We found a similar frequency of airway and respiratory adverse events leading to intervention between alfentanil and propofol used for moderate procedural sedation. Both agents appear safe for moderate procedural sedation.

Hyperbaric oxygen therapy for the prevention of arterial gas embolism in food grade hydrogen peroxide ingestion.

Food grade hydrogen peroxide ingestion is a relatively rare presentation to the emergency department. There are no defined guidelines at this time regarding the treatment of such exposures, and providers may not be familiar with the potential complications associated with high concentration hydrogen peroxide ingestions. In this case series, we describe four patients who consumed 35% hydrogen peroxide, presented to the emergency department, and were treated with hyperbaric oxygen therapy. Two of the four patients were critically ill requiring intubation. All four patients had evidence on CT or ultrasound of venous gas emboli and intubated patients were treated as if they had an arterial gas embolism since an exam could not be followed. After hyperbaric oxygen therapy each patient was discharged from the hospital neurologically intact with no other associated organ injuries related to vascular gas emboli. Hyperbaric oxygen therapy is an effective treatment for patients with vascular gas emboli after high concentration hydrogen peroxide ingestion. It is the treatment of choice for any impending, suspected, or diagnosed arterial gas embolism. Further research is needed to determine which patients with portal venous gas emboli should be treated with hyperbaric oxygen therapy.

Butyrfentanyl overdose resulting in diffuse alveolar hemorrhage.

Butyrfentanyl is a potent short-acting opioid and a fentanyl analog with uncertain clinical effects. A review of the literature reveals no human case reports of butyrfentanyl overdose. As the use of analog and synthetic drugs continues to increase, clinicians are often faced with tremendous uncertainty when they encounter patients exposed to these synthetic drugs. We describe, to our knowledge, the first case of a butyrfentanyl overdose that resulted in clinically significant hemoptysis, acute lung injury, hypoxic respiratory failure, and diffuse alveolar hemorrhage. Complicating this case was a false-positive urine drug screen for fentanyl. Clinicians who encounter fentanyl exposures should be aware they may in fact be dealing with butyrfentanyl. As little is known of butyrfentanyl and our patient suffered a significant pulmonary hemorrhage, those who encounter butyrfentanyl exposures should monitor for hemorrhagic complications.

Asystole immediately following intravenous fat emulsion for overdose.

Use of intravenous fat emulsion (IFE) for the treatment of poisoned patients in extremis is increasing. Little literature exists describing failures and complications of IFE. We describe two cardiac arrests temporally associated with IFE. A 50-year-old woman presented after ingesting 80 total tablets of metoprolol 25 mg and bupropion 150 mg. Bradycardia and hypotension were refractory to calcium salts, catecholamines, and high dose insulin (HDI). With a pulse of 40/min and mean arterial pressure (MAP) of 30 mmHg, 100 mL of 20 % IFE was given; within 30 s, brady-asystolic arrest occurred. Pulses returned after 3 min of CPR. The patient died on hospital day 4 of multisystem organ failure (MSOF). A 53-year-old man presented after ingesting of 3,600 mg of diltiazem and 1,200 mg of propranolol. Bradycardia and hypotension were refractory to calcium salts, catecholamines, HDI, bicarbonate, and atropine. With a pulse of 30/min and a MAP of 40 mmHg, 150 mL of 20 % IFE was given; within 1 min, a brady-asystolic arrest occurred. Pulses returned after 6 min of CPR. The patient died on hospital day 7 of MSOF. Reported cases of IFE failures or potential complications are sparse. This report adds only case experience, not clarity. We report two cardiac arrests that were temporally associated with IFE.

What toxicity may result from the xenobiotic responsible for the finding on this plain film? Answer: reduced iron, found in heating pads and instant hand warmers, may result in elevated serum iron concentrations and subsequent iron toxicity.

Disposable heating pads are commonly used products, with reduced iron as their active ingredient. Reduced iron is not expected to cause significant toxicity when ingested orally. We report a case of accidental heating pad ingestion seen on abdominal plain films that resulted in significantly elevated serum iron concentrations.