Comparing Intubation Rates in Patients Receiving Parenteral Olanzapine With and Without a Parenteral Benzodiazepine in the Emergency Department.

STUDY OBJECTIVE: United States prescribing information recommends against coadministration of injectable olanzapine with injectable benzodiazepines due to a risk of cardiorespiratory depression, whereas European prescribing information recommends the 2 drugs not be administered within 60 minutes of each other. In contrast, a recently published American College of Emergency Physicians clinical policy recommends injectable olanzapine and benzodiazepines be coadministered for treating severe agitation. We sought to compare injectable olanzapine with and without injectable benzodiazepines for evidence of cardiorespiratory depression. METHODS: We performed a retrospective study of patients in an urban emergency department from January 2017 through November 2019 who received parenteral olanzapine with or without parenteral benzodiazepines. We included patients receiving 2 total medication doses, either olanzapine+benzodiazepine or 2 doses of olanzapine, coadministered within 60 minutes. The primary outcome was tracheal intubation in the emergency department. Secondary outcomes included hypotension (systolic blood pressure less than 90 mmHg) and hypoxemia (SpO2 less than 90%). RESULTS: We identified 693 patients (median [alcohol]=210 mg/dL, median age=37 years [IQR 29 to 49]). In total, 549 received 2 doses of olanzapine, and 144 patients received olanzapine and a benzodiazepine. We found no difference in intubation rates between the olanzapine-only group (21/549, 3.8%) and the olanzapine+benzodiazepine group (5/144, 3.5%; difference=0.3%, 95% confidence interval -3.0% to 3.7%). Rates of hypoxemia (2% olanzapine-only and 3% olanzapine+benzodiazepine) and hypotension (9% both groups) also were not different between groups. CONCLUSION: We found no difference in cardiorespiratory depression between patients receiving only olanzapine versus olanzapine plus a benzodiazepine.

Feasibility and Safety of Oral Risperidone to Treat Prehospital Agitation.

OBJECTIVE: Agitation is a common prehospital problem and frequently presents without a clear etiology. Given the dynamic environment of the prehospital setting, there has historically been a varied approach to treating agitation with a heavy reliance on parenteral medications. Newer best practice guidelines recommend the incorporation of oral medications to treat patients experiencing agitation. Therefore, we evaluated the use of oral risperidone in a single system after a change in protocol occurred. METHODS: This was conducted as a retrospective chart review of an urban/suburban Emergency Medical Services system over the period of 8 months. The first day this medication was implemented throughout the service was included. Charts were included for selection if they included risperidone oral dissolving tablet (ODT) as a charted medication. The primary outcome was administration of additional medications to treat agitation. Exploratory outcome measures included acceptance of medication, documented injury to paramedics, documented injuries to patients, scene times, and adverse events that could possibly be linked to the medication. RESULTS: A total of 552 records were screened for inclusion. Risperidone was offered to 530 patients and accepted by 512 (96.6%). Of these 512 patients, the median age of included patients was 39 years old (IQR 29-52 years old) with a range of 18-89 years old. Rescue or additional medications for agitation were required in 9 (1.8%) cases. There were a total of 4 (0.8%) potential complications following administration of risperidone. There were no reported assaults with subsequent injuries to prehospital personnel or injuries sustained by patients reported in this study. CONCLUSIONS: Risperidone ODT was found to be a safe and effective medication to treat mild agitation in a large urban and suburban EMS system. The need for additional medications to treat agitation was rare, and there were no documented injuries to either patients or paramedics.

Massive Sodium Nitrite Overdose: A Case for Prehospital Methylene Blue.

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

Factors Associated With Physical Restraint in an Urban Emergency Department.

STUDY OBJECTIVE: To determine what patient characteristics were associated with the application of physical restraints in our emergency department (ED). METHODS: This was a retrospective analysis of encounters in the ED of an urban, Level I academic trauma center. We included ED encounters of adult patients (aged ≥18 years) during a 5-year period starting in 2017. We evaluated the independent association of restraint application during an encounter using a generalized estimating equation model. RESULTS: There were 464,031 ED encounters during the time period from 162,244 unique patients, including 34,798 (7.5%) with restraint application, comprising 18,166 unique patients. Several variables were associated with an increased likelihood of restraint use during an encounter. The variable with the highest odds ratio was intoxication with drugs or alcohol (adjusted odds ratio [aOR] 8.29; 95% confidence interval (CI) 7.94 to 8.65). American Indian race was associated with increased odds of restraint application (aOR 1.42; 95% CI 1.31 to 1.54) compared to the reference value of White race. Black race (aOR 0.58; 95% CI 0.55 to 0.61) and Hispanic ethnicity (aOR 0.42; 95% CI 0.37 to 0.48) were associated with lower odds of restraint application. CONCLUSIONS: Drug and alcohol intoxication were most closely associated with restraint. Encounters in which the patient was American Indian had higher odds of restraint, but this study does not replicate prior findings regarding other racial disparities in restraint.

American College of Medical Toxicology and the American Academy of Clinical Toxicology position statement: nalmefene should not replace naloxone as the primary opioid antidote at this time.

BACKGROUND: Nalmefene is a potent opioid antagonist that has recently been reintroduced in the United States to treat known or suspected opioid overdose. NALMEFENE CLINICAL TRIAL DATA: The injection formulation, which had been withdrawn in 2008, was reintroduced in 2022, and in 2023 the United States Food and Drug Administration approved a new intranasal formulation of nalmefene. Because nalmefene had been previously approved for use in 1995 via injection, the new intranasal formulation did not require new clinical data as it was approved under an Abbreviated New Drug Application. Inherent to this abbreviated approval process, intranasal nalmefene was not studied in patients currently suffering opioid overdose. NALOXONE AND NALMEFENE: Nalmefene also has unique characteristics compared with naloxone, the current standard opioid antidote. Nalmefene has a higher affinity for opioid receptors and a longer duration of action than naloxone. Comparative effectiveness data regarding naloxone and nalmefene are sparse, and it is unclear if the inherent properties of nalmefene are beneficial in opioid overdose. We have decades of experience using naloxone safely and effectively as the primary opioid antidote, even in cases of fentanyl and fentanyl analog overdoses. There is, however, evidence to suggest nalmefene may result in more prolonged and severe opioid withdrawal than naloxone, which could be harmful to patients. POSITION: As nalmefene is untested in the current clinical environment of synthetic opioid overdoses and has the potential to cause harm via prolonged withdrawal, it is the opinion of the American College of Medical Toxicology and the American Academy of Clinical Toxicology that nalmefene should not replace naloxone as the primary opioid antidote at this time. RECOMMENDATIONS: We recommend additional clinical studies of nalmefene, administered via all approved routes, be conducted in a comparative fashion with naloxone, and that safety and effectiveness outcomes be evaluated before nalmefene is recommended as a primary opioid antidote.

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.

QT prolongation, torsades des pointes, and cardiac arrest after 4 mg of IV ondansetron.

Ondansetron is a commonly used antiemetic in the emergency department despite a 2011 FDA warning regarding dose-related QTc prolongation and torsades des pointes (TdP). Cases of TdP from small ondansetron doses administered in the emergency department are lacking. A 41-year-old-woman with alcohol use disorder on no medications or supplements presented to an emergency department with one day of nausea, vomiting, and epigastric pain. Examination revealed a pulse of 77 beats/min and epigastric tenderness. The patient received 4 mg IV ondansetron, 30 mg IV ketorolac, and was placed on cardiac monitoring. ECG obtained one minute after ondansetron demonstrated premature ventricular contractions with QTc = 653 ms. Thirteen minutes after receiving ondansetron she suffered TdP and cardiac arrest. She received immediate CPR and IV epinephrine with successful defibrillation at one minute. She then received IV magnesium. Post-arrest ECGs demonstrated persistent QTc prolongation immediately and at three hours post-arrest. Laboratory studies, drawn prior to arrest, demonstrated hypokalemia (3.2 mEq/L), hypomagnesemia (1.3 mg/dL), and elevated lipase (4918 IU/L). She received no additional QT-prolonging agents. Transthoracic echocardiogram and troponins were normal; ECG intervals completely normalized within 12 h and she was discharged neurologically intact. The patient returned 18 months later with recurrent pancreatitis and similar electrolyte abnormalities; QT-prolonging drugs were avoided at that time and her course was uncomplicated. QT prolongation with subsequent torsades des pointes and cardiac arrest may occur in high-risk patients receiving small doses of ondansetron. Further studies are warranted to determine the safest antiemetic for use in the emergency department.

Comparison of efficacy and frequency of akathisia and dystonia between olanzapine, metoclopramide and prochlorperazine in ED headache patients.

STUDY OBJECTIVE: To compare the efficacy and frequency of akathisia and dystonia between the dopamine antagonist headache medications olanzapine, metoclopramide and prochlorperazine. METHODS: This was a retrospective observational cohort study of patients presenting to a large urban level one trauma center between 2010 and 2018. Inclusion criteria was age ≥ 18 who presented to the emergency department with a chief complaint of headache who received either olanzapine, metoclopramide or prochlorperazine. The primary outcome was need for rescue medication. Secondary outcomes were receiving medication for either akathisia or dystonia. Logistic regression was used to identify differences between the three cohorts up to 72 h from initial presentation. RESULTS: There were 5643 patients who met inclusion criteria. Olanzapine was the most commonly used drug (n = 2994, 53%) followed by prochlorperazine (n = 2100, 37%) and metoclopramide (n = 549, 10%). After adjusting for age and gender, there were no differences in risk for receiving rescue therapy or developing akathisia or dystonia. CONCLUSION: During initial ED visit and up to 72 h after receiving olanzapine, metoclopramide or prochlorperazine, we found no difference in risk for requiring rescue medication or developing akathisia or dystonia.

Recall of Awareness During Paralysis Among ED Patients Undergoing Tracheal Intubation.

BACKGROUND: Critically ill patients sometimes remember periods of neuromuscular blockade. RESEARCH QUESTION: What is the prevalence of recalled awareness during paralysis in patients who underwent emergency tracheal intubation and mechanical ventilation, and what clinical variables are associated with this outcome? STUDY DESIGN AND METHODS: This study analyzed data from a prospectively collected continuous quality improvement database of emergency tracheal intubation in an urban, county hospital. Patients who received a neuromuscular blocking agent to facilitate emergency tracheal intubation in the ED were included. The database contained details of intubation management, including medications received and patient mental status prior to intubation. Patient recall of awareness of paralysis was assessed by trained staff during an in-person interview following extubation using a modified Brice questionnaire. For this analysis, three expert reviewers used these data to adjudicate whether patients may have had awareness of paralysis, the primary outcome. A logistic regression model was constructed to determine whether clinical variables were associated with the primary outcome. RESULTS: A total of 886 patients were analyzed. There were 66 patients (7.4%; 95% CI, 5.8-9.4) determined to possibly (61 patients) or definitely (5 patients) have experienced and recalled awareness of paralysis. A logistic regression model revealed that a decreased level of consciousness prior to intubation was associated with lower odds of awareness (adjusted OR, 0.39; 95% CI, 0.22-0.69), whereas the class of neuromuscular blocking agent used, sedative used, preintubation shock index, and postintubation sedation were not significantly associated with recall of this outcome. INTERPRETATION: Among patients intubated emergently using a neuromuscular blocking agent, 7.4% of patients recalled awareness without being able to move, which was more likely when patients had a normal level of consciousness prior to intubation.

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.

Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines.

Background: High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning.Methods: This was a retrospective study from a single poison center. Cases were identified via the generic code "Calcium Antagonists" in which the therapy "High Dose Insulin/Glucose" was "performed, whether or not recommended" from 2019-2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia.Results: Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil n = 10, diltiazem n = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2-5; range 0-6) and 2 in the non-DHP group (IQR: 1-3; range 0-5; p = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0-2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min; p = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0; p = 0.009).Conclusions: Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.

Cardiotoxic Medication Poisoning.

Beta-blockers and calcium channel blockers result in a disproportionate number of fatalities from cardiac medication overdoses, and share similar characteristics. High-dose insulin is a superior therapy for both overdoses, but is likely synergistic with vasopressors; therefore we recommend starting vasopressors and high-dose insulin simultaneously. Digoxin remains an important cardiac poison and can likely be safely treated with smaller doses of fab fragments than in the past, except for patients in extremis. Extracorporeal membrane oxygenation is an invasive but promising nonspecific therapy for refractory shock from cardiotoxic overdose and should be considered primarily in cases of refractory cardiogenic shock.