Analysis of rising cases of adolescent opioid use presentations to the emergency department and their management.

OBJECTIVE: We sought to answer the question of how adolescents (ages 12-17 years old) with opioid-related presentations are currently managed in the ED. The two main outcomes were the proportion of visits where naloxone and buprenorphine were both used and prescribed, and the rate of revisits to the emergency department in the six months following ED presentation. METHODS: This was a multi-center retrospective cross-sectional study. We studied patients presenting to the ED who were 12-17 years old with an opioid-related presentation. RESULTS: Two-hundred and thirty-one patients were identified out of 571 encounters screened. Of these presentations, 77/231 (33%) were girls and 154/231 (67%) were boys. The majority of patients were Latino (64%; n=147); 26% were white (n=59), 6% were middle eastern or Arab (14), and 4% were black (10). Incidence of opioid use disorder per 100,000 presentations increased by 2800% from 2014 to 2022 (21/100,000 +/- 10 [2014] to 600/100,000 +/- 50 [2022]). A plurality of cases was related to opioid withdrawal (42%; 97). On discharge from the ED, 29% of patients received naloxone. For patients in withdrawal, 4% received a prescription for buprenorphine. Twenty-nine percent of patients had a return to the ED in the six months following initial visit. CONCLUSIONS: Adolescent opioid-related presentations to the ED are rapidly increasing. Increasing ED presentations, compounded by a high 6-month revisit rate, pose a management challenge amid limited outpatient resources for this population. Opioid agonist therapy and naloxone are not routinely provided. Increasing the use of both are two ways to improve the quality of care for this population.

Hyperammonemia in acetaminophen toxicity.

INTRODUCTION: Acetaminophen-induced hepatotoxicity can result in hyperammonemia, but it is not clear if elevated ammonia concentrations predict encephalopathy. METHODS: We retrospectively studied patients with acetaminophen toxicity at a liver transplant center over 8 years (January 1, 2010-December 31, 2017), who developed hepatotoxicity (AST and/or ALT >1000 IU/L) or hyperammonemia (ammonia > 40 µmol/L). We recorded baseline characteristics, laboratory data, documented grade of encephalopathy, and treatments administered. Sensitivity and specificity values were calculated for varying ammonia concentrations. RESULTS: A total of 102 patient encounters were included with 75 having ammonia concentrations. On presentation, 40% (30/75) of patients had concentrations greater than 100 µmol/L. However, an [ammonia] > 100 µmol/L was neither sensitive (46 % [95% CI: 26-67%]) nor specific (63% [48 - 76%]) for encephalopathy. Only an increasing ammonia concentration had a significant, but small (1.53 (95% CI: 1.06 - 2.20)) positive likelihood ratio for the development of hepatic encephalopathy. DISCUSSION: Animal models have suggested that in acetaminophen toxicity, encephalopathy may be secondary to an alternative mechanism other than hyperammonemia which may explain the lack of correlation between initial hyperammonemia and encephalopathy in this cohort. Additionally, a lack of empiric treatment for hyperammonemia did not appear to alter the course of any of the patients. None of these patients developed encephalopathy. CONCLUSION: In cases of acetaminophen-induced hepatotoxicity, ammonia concentrations do not correlate with encephalopathy and empiric treatment for hyperammonemia does not appear to be beneficial.

Single versus continued dosing of fomepizole during hemodialysis in ethylene glycol toxicity.

BACKGROUND: In cases of ethylene glycol (EG) toxicity requiring hemodialysis (HD), fomepizole is dosed every four hours. HD efficiently clears EG and its toxic metabolites, and it's unclear if multiple doses (MD) of fomepizole improve patient outcomes or whether a single dose (SD) prior to initiation of HD is sufficient. METHODS: We reviewed cases of EG toxicity at a toxicology referral center from 2008 to 2018. Patients treated with HD with EG levels greater than 20 mg/dL were included. Duration of dialysis, creatinine at discharge, hospital length of stay (LOS), and complications were analyzed. We compared patients who received a single dose of fomepizole prior to HD to those who received continued dosing during and after HD. RESULTS: Twenty-five patient encounters were identified (MD: 20; SD: 5). Initial bicarbonate (11 [SD] vs. 9 mg/dL [MD]) and pH (7.1 vs. 7.1) were similar between the groups; however, there was a trend toward a greater proportion of patients with renal dysfunction in the MD group: 11 (55%) vs. 1 (20%). HD was initiated a median interval of 5.2 h [SD] vs. 5.7 h [MD] after a dose of fomepizole. There was one death in the MD group and none in the SD group. Median creatinine on the day of discharge was 0.7 mg/dL (IQR: 0.57-3.8) in the SD group and 2.0 mg/dL (0.90-7.0) in the MD group. LOS was similar (5.8 days [95% CI 3.6-8.0] vs. 7.6 days [5.3-9.9]) (p = .61). CONCLUSION: Patients with moderately severe EG toxicity (acidosis and no initial renal dysfunction) treated with a single dose of fomepizole prior to HD had similar outcomes to those receiving continued dosing of fomepizole during or after HD. This raises the possibility that a single dose of fomepizole may be sufficient if HD is initiated quickly.

Fentanyl panic goes viral: The spread of misinformation about overdose risk from casual contact with fentanyl in mainstream and social media.

BACKGROUND: Fueled by misinformation, fentanyl panic has harmed public health through complicating overdose rescue while rationalizing hyper-punitive criminal laws, wasteful expenditures, and proposals to curtail vital access to pain pharmacotherapy. To assess misinformation about health risk from casual contact with fentanyl, we characterize its diffusion and excess visibility in mainstream and social media. METHODS: We used Media Cloud to compile and characterize mainstream and social media content published between January 2015 and September 2019 on overdose risk from casual fentanyl exposure. RESULTS: Relevant content appeared in 551 news articles spanning 48 states. Misinformed media reports received approximately 450,000 Facebook shares, potentially reaching nearly 70,000,000 users from 2015-2019. Amplified by erroneous government statements, misinformation received excess social media visibility by a factor of 15 compared to corrective content, which garnered fewer than 30,000 shares with potential reach of 4,600,000 Facebook users. CONCLUSION: Health-related misinformation continues to proliferate online, hampering responses to public health crises. More evidence-informed tools are needed to effectively challenge misinformed narratives in mainstream and social media.

Feasibility of Intermittent Hemodialysis in Metformin Toxicity With Shock.

BACKGROUND: Metformin toxicity can lead to profound shock and has a high mortality rate. Supportive care and enhanced elimination are the mainstays of therapy. Intermittent hemodialysis (HD) produces a higher clearance of metformin than continuous veno-venous hemofiltration or hemodiafiltration (CVVH/HDF). Nevertheless, CVVH/HDF has been proposed as an alternative in critically ill patients with the suggestion that hypotension may limit the use of HD. OBJECTIVE: This study sought to analyze the feasibility of performing hemodialysis in patients with persistent shock from metformin toxicity. METHODS: We performed a 6-year (2012-2017) retrospective chart review of patients with metformin toxicity managed at a large academic institution with a toxicology service. We included patients with persistent shock on vasopressor support who were treated with HD. Baseline characteristics, complications from treatment, timing of dialysis, and differences between mean arterial pressures before, during, and at the end of dialysis were recorded and analyzed. RESULTS: Despite critical mean peak lactate (23.9 mMol/L [range 17.6-27.9]), pH (6.91 [range 6.78-7.01]), and metformin levels (range 25-58 µg/mL], 6 of 7 patients recovered. All patients required prolonged HD (mean 19 h). Upon completion of HD, hemodynamics had improved (45 mm Hg [95% confidence interval 35-55 mm Hg] vs. 80 mm Hg [95% confidence interval 74-86 mm Hg]) and vasopressor support decreased. Mortality in this patient cohort was 14.3% (1/7). CONCLUSION: Intermittent HD is feasible in metformin toxicity despite persistent shock and high-dose vasopressor support. Mean arterial pressures improved during the course of HD and high blood flow rates were tolerated.

Serotonin toxicity from isolated bupropion overdoses.

Background: Bupropion is a synthetic cathinone, which acts therapeutically through norepinephrine and dopamine reuptake inhibition. Recent evidence suggests that serotonin receptor activation occurs with high doses of bupropion and severe serotonin toxicity can occur after isolated bupropion overdoses. Prior observational studies may therefore underestimate the incidence of serotonin toxicity.Methods: A retrospective study of patients with bupropion toxicity at a toxicology referral center from 2015-2017 was performed. Patients who overdosed on other serotonergic medications were excluded. Serotonin toxicity was diagnosed retrospectively using Hunter Criteria.Results: Overall, 96 patients were identified with bupropion toxicity. Of these, 18 patients ingested bupropion in the absence of other serotonergic drugs. The incidence of serotonin toxicity was 33% in this population. Serotonin toxicity was more likely after a suicide attempt than those with an accidental ingestion or after recreational drug use. The median dose of bupropion ingested was 2,250 mg in the cohort diagnosed with serotonin syndrome.Conclusion: The incidence of bupropion induced serotonin toxicity is higher than reported. Clinicians should monitor for serotonergic toxicity when evaluating patients after bupropion overdose.

Do electronic health record prompts increase take-home naloxone administration for emergency department patients after an opioid overdose?

BACKGROUND AND AIMS: Distribution of take-home naloxone (THN) to emergency department (ED) patients who have survived an opioid overdose (OD) could reduce future opioid mortality, but is not commonly performed. We examined whether electronic health record (EHR) prompts provided to ED physicians when discharging a patient after an OD could improve THN distribution. DESIGN: Interrupted time-series analysis to compare the percentage of OD patients who received THN during the 11 months before and after implementation of an EHR prompt on 18 June 2017. SETTING AND PARTICIPANTS: A total of 3492 adult patients with diagnoses of OD discharged from nine EDs in a single health system in Western Pennsylvania from July 2016 to April 2018. INTERVENTION AND COMPARATOR: The EHR prompt was triggered by the presence of specific terms in the nurse's initial assessment note. The EHR displayed a pop-up window during the ED physician discharge process asking the physician to consider prescribing or providing naloxone to the patient. The comparator was 'no EHR prompt'. MEASUREMENTS: Measurements were based on standard criteria from ICD diagnostic codes and chief complaint keywords. FINDINGS: In July 2016, 16.3% [95% confidence interval (CI) = 14.0, 18.5] of OD patients received THN, which decreased every month through June 2017 by 1.2% (P < 0.0001, 95% CI = 0.8,1.7). For each month post-EHR prompt there was an increase of 2.8% of OD patients receiving THN (P < 0.001, 95% CI = 2.0, 3.5). No increases occurred in the ED with the highest pre-EHR prompt THN distribution. Rates of THN distribution varied by patient age and race prior to, but not after, implementation of EHR prompts. CONCLUSIONS: Electronic health record prompts are associated with increased take-home naloxone distribution for emergency department patients discharged after opioid overdoses.

Neurotoxic envenomation by the South African coral snake (Aspidelaps lubricus): A case report.

The South African coral snake (Aspidelaps lubricus, Elapidae) has not previously been reported to cause any neurotoxic envenomations in humans. We recently treated a 44-year-old man who was bitten twice, once in each hand, by a captive South African coral snake (Aspidelaps lubricus) while feeding the female snake who had recently laid eggs. Approximately one hour after receiving the bite, he developed vomiting, respiratory failure requiring mechanical ventilation, and paralysis of the bulbar and upper extremity muscles, with retention of voluntary motor control in the lower extremities. Supportive care was provided, and paralysis and respiratory failure resolved spontaneously 12 hours after onset. No antivenom for this species is available. To our knowledge, this is the first published case report of significant human envenomation by Aspidelaps lubricus. Physicians, first responders, and herpetologists should be aware of the potential for neurotoxicity in humans.

Multimodal analgesia in crotalid snakebite envenomation: A novel use of femoral nerve block.

Snakebite envenomations occur throughout the United States, with most envenomations resulting from Crotalid bites. These envenomations can result in severe pain despite aggressive analgesia due to effects of venom toxins. We report a case in which we treated a 44- year-old man who sustained a Copperhead (Agkistrodon contortrix) bite to his left hallux with progressive local toxicity, including severe pain radiating into his upper leg, without evidence of compartment syndrome or coagulopathy. His pain was unresponsive to multiple doses of opioids. We performed a fascia iliaca compartment femoral nerve block under dynamic ultrasound guidance with 20 mL of 0.25% bupivacaine, which provided substantial pain relief in his upper leg. To our knowledge, this is a novel application of regional anesthesia with peripheral nerve block. We demonstrate fascia iliaca compartment femoral nerve block may be a safe, beneficial technique for emergency physicians to utilize in providing multimodal analgesia in Crotalid envenomation.

Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis.

Factors regulating the proliferation and apoptosis of intestinal stem cells (ISCs) remain incompletely understood. Because ISCs exist among microbial ligands, immune receptors such as toll-like receptor 4 (TLR4) could play a role. We now hypothesize that ISCs express TLR4 and that the activation of TLR4 directly on the intestinal stem cells regulates their ability to proliferate or to undergo apoptosis. Using flow cytometry and fluorescent in situ hybridization for the intestinal stem cell marker Lgr5, we demonstrate that TLR4 is expressed on the Lgr5-positive intestinal stem cells. TLR4 activation reduced proliferation and increased apoptosis in ISCs both in vivo and in ISC organoids, a finding not observed in mice lacking TLR4 in the Lgr5-positive ISCs, confirming the in vivo significance of this effect. To define molecular mechanisms involved, TLR4 inhibited ISC proliferation and increased apoptosis via the p53-up-regulated modulator of apoptosis (PUMA), as TLR4 did not affect crypt proliferation or apoptosis in organoids or mice lacking PUMA. In vivo effects of TLR4 on ISCs required TIR-domain-containing adapter-inducing interferon-ß (TRIF) but were independent of myeloid-differentiation primary response-gene 88 (MYD88) and TNFα. Physiological relevance was suggested, as TLR4 activation in necrotizing enterocolitis led to reduced proliferation and increased apoptosis of the intestinal crypts in a manner that could be reversed by inhibition of PUMA, both globally or restricted to the intestinal epithelium. These findings illustrate that TLR4 is expressed on ISCs where it regulates their proliferation and apoptosis through activation of PUMA and that TLR4 regulation of ISCs contributes to the pathogenesis of necrotizing enterocolitis.

Massive transfusion: an evidence-based review of recent developments.

The design and implementation of massive transfusion protocols with ratio-based transfusion of blood and blood products are important and active areas of investigation. A significant yet controversial body of literature exists to support the use of hemostatic resuscitation in massive transfusion and new data to support the use of adjuncts, such as recombinant factor VIIa and tranexamic acid. We review the developments in massive transfusion research during the past 5 years, including protocol implementation, hemostatic resuscitation, the use of tranexamic acid, and goal-directed therapy for coagulopathy. Furthermore, we provide a level of evidence analysis of the data surrounding the use of component therapy and recombinant factor VIIa in massive transfusion, summary recommendations for the various agents of resuscitation, and new methods of goal-directed therapy.