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.

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.

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.

Naloxone-associated pulmonary edema following recreational opioid overdose.

OBJECTIVE: Describe a series of patients who developed naloxone-associated pulmonary edema after recreational opioid use. DESIGN: Single center retrospective case series of patients who developed pulmonary edema following the prehospital administration of naloxone. SETTING: Academic, urban safety-net hospital. PATIENTS: Adults with recreational opioid overdose who developed naloxone-associated pulmonary edema, defined as the acute onset of respiratory distress, hypoxemia, and radiographic pulmonary edema after naloxone administration for opioid intoxication, provided that gas exchange and chest imaging rapidly improved and pulmonary aspiration of gastric contents was not clinically suspected. MEASUREMENTS AND MAIN RESULTS: Ten adults (median age 23 years, 90% male) met our case definition for naloxone-associated pulmonary edema. Implicated opioids were heroin in 8 patients and methadone and oxycodone in 1 patient each. The median total dose of naloxone was 4.25 mg (interquartile range [IQR] 3.3-9.8) prior to the onset of clinically-apparent pulmonary edema. Seven patients received invasive mechanical ventilation for a median of two days (IQR 0.8-5), one of whom received veno-venous extracorporeal membrane oxygenation support, and all survived to hospital discharge. CONCLUSIONS: Severe acute pulmonary edema may follow naloxone administration after recreational opioid overdose. Acute care clinicians should be aware of this potentially life-threatening adverse effect of naloxone.

Characterization of Regional Poison Center Utilization Through Geospatial Mapping.

INTRODUCTION: Penetrance is the annual rate of human exposure calls per 1000 persons, a measure that historically describes poison center (PC) utilization. Penetrance varies by sociodemographic characteristics and by geography. Our goal in this study was to characterize the geospatial distribution of PC calls and describe the contribution of geospatial mapping to the understanding of PC utilization. METHODS: This was a single-center, retrospective study of closed, human, non-healthcare facility exposure calls to a regional PC over a five-year period. Exposure substance, gender, age, and zone improvement plan (ZIP) Code were geocoded to 2010 US Census data (household income, educational attainment, age, primary language) and spatially apportioned to US census tracts, and then analyzed with linear regression. Penetrance was geospatially mapped and qualitatively analyzed. RESULTS: From a total of 304,458 exposure calls during the study period, we identified 168,630 non-healthcare exposure calls. Of those records, 159,794 included ZIP Codes. After exclusions, we analyzed 156,805 records. Penetrance ranged from 0.081 - 38.47 calls/1000 population/year (median 5.74 calls/1000 persons/year). Regression revealed positive associations between >eighth-grade educational attainment (ß = 5.05, p = 0.008), non-Hispanic Black (ß = 1.18, p = 0.032) and American Indian (ß = 3.10, p = 0.000) populations, suggesting that regions with higher proportions of these groups would display greater PC penetrance. Variability explained by regression modelling was low (R2 = 0.054), as anticipated. Geospatial mapping identified previously undocumented penetrance variability that was not evident in regression modeling. CONCLUSION: PC calls vary substantially across sociodemographic strata. Higher proportions of non-Hispanic Black or American Indian residents and >eighth-grade educational attainment were associated with higher PC call penetrance. Geospatial mapping identified novel variations in penetrance that were not identified by regression modelling. Coupled with sociodemographic correlates, geospatial mapping may reveal disparities in PC access, identifying communities at which PC resources may be appropriately directed. Although the use of penetrance to describe PC utilization has fallen away, it may yet provide an important measure of disparity in healthcare access when coupled with geospatial mapping.

Persistent Hyperinsulinemia Following High-Dose Insulin Therapy: A Case Report.

INTRODUCTION: Overdoses of beta-adrenergic antagonists and calcium channel antagonists represent an uncommonly encountered but highly morbid clinical presentation. Potential therapies include fluids, calcium salts, vasopressors, intravenous lipid emulsion, methylene blue, and high-dose insulin. Although high-dose insulin is commonly used, the kinetics of insulin under these conditions are unknown. CASE REPORT: We present a case of a 51-year-old male who sustained a life-threatening overdose after ingesting approximately 40 tablets of a mixture of amlodipine 5 mg and metoprolol tartrate 25 mg. Due to severe bradycardia and hypotension, he was started on high-dose insulin (HDI) therapy; this was augmented with epinephrine. Despite the degree of his initial shock state, he ultimately recovered, and HDI was discontinued. Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter. CONCLUSION: The kinetics of insulin following discontinuation of high-dose insulin therapy are largely unknown, but supraphysiologic insulin levels persist for some time following therapy; this may allow for simple discontinuation rather than titration of insulin at the end of therapy. Dextrose replacement is frequently needed; although the duration is often difficult to predict, prolonged infusions may not be necessary.

Extracorporeal Membrane Oxygenation for Poisonings Reported to U.S. Poison Centers from 2000 to 2018: An Analysis of the National Poison Data System.

OBJECTIVES: To assess trends in the use of extracorporeal membrane oxygenation for poisoning in the United States. DESIGN: Retrospective cohort study. SETTING: The National Poison Data System, the databased owned and managed by the American Association of Poison Control Centers, the organization that supports and accredits all 55 U.S. Poison Centers, 2000-2018. PATIENTS: All patients reported to National Poison Data System treated with extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 407 patients met final inclusion criteria (332 adults, 75 children). Median age was 27 years (interquartile range, 15-39 yr); 52.5% were male. Median number of ingested substances was three (interquartile range, 2-4); 51.5% were single-substance exposures. Extracorporeal membrane oxygenation use in poisoned patients in the United States has significantly increased over time (z = 3.18; p = 0.001) in both adults (age > 12 yr) and children (age ≤ 12 yr), increasing by 9-100% per year since 2008. Increase in use occurred more commonly in adults. We found substantial geographical variation in extracorporeal membrane oxygenation use by geospatially mapping the ZIP code associated with the initial call, with large, primarily rural areas of the United States reporting no cases. Overall survival was 70% and did not vary significantly over the study period for children or adults. Patients with metabolic and hematologic poisonings were less likely to survive following extracorporeal membrane oxygenation than those with other poisonings (49% vs 72%; p = 0.004). CONCLUSIONS: The use of extracorporeal membrane oxygenation to support critically ill, poisoned patients in the United States is increasing, driven primarily by increased use in patients greater than 12 years old. We observed no trends in survival over time. Mortality was higher when extracorporeal membrane oxygenation was used for metabolic or hematologic poisonings. Large, predominantly rural regions of the United States reported no cases of extracorporeal membrane oxygenation for poisoning. Further research should focus on refining criteria for the use of extracorporeal membrane oxygenation in poisoning.

The Hennepin Ketamine Study Investigators' Reply.

We read with interest the recent editorial, "The Hennepin Ketamine Study," by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton's editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton's editorial, and to the lay media stories on which it appears to be based.Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators' reply. Prehosp Disaster Med. 2019;34(2):111-113.

Ten Years of Robotripping: Evidence of Tolerance to Dextromethorphan Hydrobromide in a Long-Term User.

INTRODUCTION: Dextromethorphan hydrobromide is widely available as an over-the-counter cough suppressant. A semi-synthetic opioid displaying N-methyl-D-aspartate receptor antagonism, it is commonly abused for recreational purposes. Spuriously elevated serum chloride concentrations are a well-described phenomenon in the setting of dextromethorphan hydrobromide toxicity, but evidence to suggest the development of tolerance is limited to case reports. CASE: A 32-year-old male known to chronically ingest dextromethorphan hydrobromide for recreational purposes presented to regional hospitals on 179 occasions over 110 months and was treated for dextromethorphan toxicity on 163/174 (93.7%) of these visits. He reported a subjective need to increase his dosing over time to achieve the same degree of intoxication. Measured serum chloride over this period (n = 217) ranged from 98 to 138 mEq/L (median 115 mEq/L, IQR 110-123 mEq/L). Measured concentrations over the 110-month period progressively rose, with a fitted plot of 111.15 + 0.00232x describing the rise in measured chloride. Though not formally assessed, anion gaps tended to become progressively more negative over the observed period. DISCUSSION: We report a patient with persistent dextromethorphan hydrobromide abuse at escalating doses whose mean serum chloride concentration increased, on average, by 0.00232 mEq/L every day over a 110-month period. This case demonstrates progressive spurious hyperchloremia secondary to bromide interference in hospital-based chloride assays, supporting the patient's reported need to dose escalate to the same desired effect. Although this artefactual laboratory finding is a well-documented result of bromide ingestion, it may be useful in identifying patterns of dextromethorphan hydrobromide use that suggest tolerance.

Physostigmine is superior to non-antidote therapy in the management of antimuscarinic delirium: a prospective study from a regional poison center.

CONTEXT: Poison centers (PCs) frequently manage patients with antimuscarinic delirium. However, controversy surrounds the antidotal use of physostigmine for its treatment. The aim of this study was to prospectively investigate physostigmine versus non-antidote therapy for the management of antimuscarinic delirium in a single regional PC. METHODS: This was a prospective observational analysis of patients diagnosed with antimuscarinic delirium and treated in consultation with a regional PC. Certified Specialists in Poison Information (CSPIs) use a clinical guideline to recommend the use of physostigmine. Using a previously derived altered mental status score, we quantified the rate of delirium improvement with physostigmine compared to non-antidote therapy two hours after initial patient identification. We also recorded adverse events (defined a priori as bradycardia, vomiting, seizures) and resource utilization (intubation and physical restraint). RESULTS: We identified 245 patients and included 154 in the analysis. The most common exposure classes were antihistamines (68%), analgesics (19%), and antipsychotics (19%). CSPIs recommended physostigmine in 81% (125) of cases and the treatment team administered it in 37% (57) of these. We observed delirium control in 79% of patients who received physostigmine versus 36% of those who did not. The odds of delirium control were six times greater for patients receiving physostigmine than for patients treated with non-antidote therapy (OR 6.6). Adverse events were rare and did not differ significantly between the groups. Physostigmine was not associated with changes in the incidence of intubation or restraint. CONCLUSIONS: This study provides further evidence of both the safety and efficacy of physostigmine in the treatment of antimuscarinic delirium.

High dose insulin for beta-blocker and calcium channel-blocker poisoning.

BACKGROUND/OBJECTIVES: High dose insulin (HDI) is a standard therapy for beta-blocker (BB) and calcium channel-blocker (CCB) poisoning, however human case experience is rare. Our poison center routinely recommends HDI for shock from BBs or CCBs started at 1U/kg/h and titrated to 10U/kg/h. The study objective was to describe clinical characteristics and adverse events associated with HDI. METHODS: This was a structured chart review of patients receiving HDI for BB or CCB poisoning with HDI defined as insulin infusion of ≥0.5U/kg/h. RESULTS: In total 199 patients met final inclusion criteria. Median age was 48years (range 14-89); 50% were male. Eighty-eight patients (44%) were poisoned by BBs, 66 (33%) by CCBs, and 45 (23%) by both. Median nadir pulse was 54 beats/min (range 12-121); median nadir systolic blood pressure was 70mmHg (range, 30-167). Forty-one patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus was 1U/kg (range, 0.5-10). Median starting insulin infusion was 1U/kg/h (range 0.22-10); median peak infusion was 8U/kg/h (range 0.5-18). Hypokalemia occurred in 29% of patients. Hypoglycemia occurred in 31% of patients; 50% (29/50) experienced hypoglycemia when dextrose infusion concentration ≤10%, and 30% (31/105) experienced hypoglycemia when dextrose infusion concentration ≥20%. CONCLUSIONS: HDI, initiated by emergency physicians in consultation with a poison center, was feasible and safe in this large series. Metabolic abnormalities were common, highlighting the need for close monitoring. Hypoglycemia was more common when less concentrated dextrose maintenance infusions were utilized.

The Association of Emergency Department Treatments for Hyperglycemia with Glucose Reduction and Emergency Department Length of Stay.

BACKGROUND: Hyperglycemia is frequently encountered in the emergency department (ED), and insulin and intravenous fluid are commonly administered to reduce glucose prior to discharge. OBJECTIVES: We sought to determine the magnitude of the association between glucose-lowering therapies and 1) actual glucose reduction and 2) ED length of stay (LOS). METHODS: We performed a retrospective chart review study of patients with any glucose level ≥ 400 mg/dL who were discharged from the ED between January 2010 and December 2011. Generalized estimating equation models were created for the ED outcomes of glucose reduction and ED LOS with primary predictors of insulin and intravenous fluids administered. RESULTS: The cohort consisted of 422 patients with 566 encounters. Median arrival and discharge glucose were 473 mg/dL and 326 mg/dL, respectively, with median glucose reduction of 144 mg/dL. Median length of stay was 253 min. After adjustment, 10 units of subcutaneous insulin and 1 liter of intravenous fluid were associated with 33 mg/dL and 27 mg/dL glucose reduction, respectively. Every liter of intravenous fluid administered was associated with a 45-min increase in ED LOS; insulin administration was not associated with ED LOS. CONCLUSION: In patients with type 2 diabetes who present with moderate to severe hyperglycemia, both insulin and intravenous fluids are associated with a modest glucose reduction. Intravenous fluids were associated with a significant increase in ED LOS, but insulin was not. These results should be considered when determining whether to administer therapies that reduce glucose in the ED.

Unexpected Complication of Cocaine-Associated Anti-Neutrophil Cytoplasmic Antibody Vasculitis Related to Persistent In-Hospital Cocaine Use.

INTRODUCTION: Levamisole-adulterated cocaine has been implicated in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. We present a case of spontaneous intraperitoneal hemorrhage, an unexpectedly severe complication of cocaine-related ANCA vasculitis, developing late during hospitalization. CASE REPORT: An adult male with a history of hepatitis C, distant cocaine use, and limited health care presented to a local emergency department (ED) with volume overload, renal failure, hyperkalemia and non-anion gap metabolic acidosis. An extensive workup ensued, followed by pulse-dose methylprednisolone and plasma exchange for ANCA vasculitis with crescentic glomerulonephritis. Tachycardia and hypertension persisted throughout hospitalization despite treatment. On hospital day (HD) 13, his abdomen became distended and tender. Mental status and blood pressure declined, and he was emergently intubated. Paracentesis revealed frank blood; hemoglobin declined from 10.6 to 4.6 g/dL during 10 hours. Laparotomy revealed 3.5 L of intraperitoneal blood and a bleeding omental vessel. Histopathology revealed necrotic aneurysmal dilatation diagnostic of systemic vasculitis. Urine cocaine metabolite was positive on HD #13, consistent with the patient's report of in-hospital cocaine use. He was discharged on HD #28 without further complications with plans for outpatient hemodialysis. DISCUSSION: ANCA vasculitis is widely reported following levamisole-adulterated cocaine use. Catastrophic in-hospital hemorrhage due to ANCA vasculitis and vascular necrosis, though previously unreported, may occur with ongoing cocaine use.