A Narrative Review of Aconite Poisoning and Management.

Aconite poisoning refers to toxicity resulting from plants belonging to the Aconitum genus, which comprises over 350 different species of perennial flowering plants that grow in temperate mountainous areas of the northern hemisphere (North America, Europe, Asia). These plants contain a group of toxins known as aconite alkaloids, which encompass numerous closely related toxic compounds. Conventional teaching from toxicology textbooks has broadly classified these alkaloids based on their mechanism of action, often simplifying them as substances that prevent sodium channel inactivation. However, this is an oversimplified and sometimes inaccurate description, as some aconite alkaloids can act as sodium channel blockers. Aconite alkaloids have a long history of use as poisonous substances and have been historically employed for hunting, assassinations, traditional medicine, and self-inflicted harm. Toxicity can occur due to the consumption of traditional medicines derived from aconitum plants or the ingestion of aconite plants and their derivatives. The clinical manifestations of aconite poisoning may encompass gastrointestinal symptoms, sensory alterations, seizures, and life-threatening dysrhythmias that may not respond to standard treatments. Treatment is primarily supportive however evaluation and management of these patients should be personalized and carried out in collaboration with a toxicologist.

The incidence of self-harm ingestions in adolescents and young adults at a tertiary care center.

BACKGROUND: There has been an increasing incidence of self-harm attempts in recent years in the United States. Particularly concerning, there has been a growing trend of self-harm in the adolescent and young adult population. In order to inform initiatives to address this trend, risk factors and substances used for self-harm need to be clarified. METHODS: This is a descriptive retrospective observational study on all cases of self-harm poisoning in patients between the ages of 12 and 25 years reported at the state's only tertiary care center from January 2019 through March 2022. RESULTS: There was an increased incidence of 69% for self-harm poisonings for all ages and a 90% increase in ages 12-17 years between the years 2019 and 2021. Fifty percent of all cases occurred in patients aged 14-17 years, 69% were female, and 22% required an intensive care unit. The top three most common substances used are available without a prescription. DISCUSSION: There was a persistent increase in self-harm attempts via poisoning throughout the study period with a particularly vulnerable period in the adolescent age group.

Severe chronic Carboxyhemoglobinemia and polycythemia due to smoking hookah.

Acute carbon monoxide (CO) poisoning due to smoking hookah has been reported and may present similarly to other causes of acute carbon monoxide poisoning with nausea, headache, and loss of consciousness [1]. In the acute poisoned patient, immediate removal from the carbon monoxide source is paramount in addition to administration of oxygen and possible hyperbaric oxygen therapy (HBO) in certain situations. However, cases of chronic CO poisoning, treatment options, and long-term adverse health effects are far less reported but may include atherosclerosis and vague neurologic symptoms [2]. We present a case of a patient who chronically smoked hookah creating a condition of chronic carboxyhemoglobinemia which was discovered during work up for unexplained polycythemia. While being seen in the hematology clinic, he was found to have a blood carboxyhemoglobin of level 33.6% despite being asymptomatic. This is the highest recorded hookah-related carboxyhemoglobin concentration in the medical literature; and the significant chronic carboxyhemoglobinemia explained his polycythemia. This case illustrates that a social history is crucial when assessing the patient with severe carboxyhemoglobinemia as HBO is not indicated in chronic CO poisoning in an asymptomatic patient.

Disposition, outcomes, and lengths of stay due to bupropion overdose at a tertiary care center with a medical toxicology service.

INTRODUCTION: Bupropion is an antidepressant with unique mechanisms of action leading to a narrow therapeutic window. Parallel to increasing indications, there is an increasing number of overdoses and fatalities attributable to bupropion overdose. Due to the serious effects of a bupropion overdose including arrhythmias and early or delayed seizures, these patients necessitate prolonged monitoring with high levels of medical care. In the setting of a tertiary care center with a medical toxicology consult service, our institution is heavily relied upon to manage these patients. This study was performed to provide clarity on the resources used, lengths-of-stay, and treatments provided for these patients. METHODS: All patients at a tertiary care center with an oral bupropion overdose and a medical toxicology consult less than 24 h after the ingestion were included between July 15, 2017 and October 14, 2021. Chart review was performed to determine lengths-of-stay, the unit of disposition, treatments provided, and outcomes. RESULTS: A total of 73 cases were identified with 36 bupropion-only ingestions. Most cases were transferred from outside facilities, developed seizures, had QRS prolongation; and almost a third required intubation. The vast majority were admitted to an ICU and received GABA-A agonists. A median of 1.47 days per case was spent in the ED or ICU. There was an average of 41.9 ED or ICU bed-days per year and 68.5 non-psychiatric bed-days per year occupied by a patient after a bupropion overdose at a single center. CONCLUSIONS: Bupropion overdose necessitates high resource utilization which we believe will increase with the expanding indications for its use.

Flecainide poisoning and prolongation of elimination due to alkalinization.

BACKGROUND: Flecainide is a 1C antidysrhythmic that is primarily used for ventricular tachycardia or premature ventricular contractions when other treatment is ineffective. It has a very narrow therapeutic window which may cause death in a double dose and requires inpatient initiation for cardiac monitoring. Despite established pharmacokinetic data from flecainide in therapeutic dosing, there is negligible data on flecainide toxicokinetics after an intentional overdose. Due to the inherent differences in pharmacokinetic and toxicokinetic principles, rarely can the peak effect or elimination half-life accurately be applied to the poisoned patient after an overdose. In overdose, flecainide can cause a variety of fatal dysrhythmias which may require sodium bicarbonate for stabilization but also may reduce the renal elimination of flecainide, meaning the life-saving treatment may prolong the time of toxicity. CASE REPORT: We present a case of an acute ingestion of flecainide with a known time of ingestion and known amount of ingestion who experienced subsequent life-threatening effects which required endotracheal intubation, sodium bicarbonate, aggressive electrolyte repletion, and multiple days in an intensive care unit. RESULTS: Serial serum and urine samples revealed a prolonged toxic serum concentration of flecainide. CONCLUSION: These results demonstrate the change in elimination kinetics of flecainide in the setting of urinary alkalization which is evident through prolonged morphologic changes present on serial electrocardiograms.

The Timing of Clinical Effects of Bupropion Misuse Via Insufflation Reported to a Regional Poison Center.

BACKGROUND: Bupropion is an antidepressant medication with expanding indications including smoking cessation, weight loss, attention-deficit/hyperactivity disorder, seasonal affective disorder, and amphetamine dependence. Despite its increasing popularity among providers, it has a well-known narrow therapeutic window that can lead to delayed onset of symptoms with extended-release formulations and devastating consequences in overdose. We have noticed some patients misusing bupropion via insufflation, which added a layer of complexity with regards to the therapeutic application of the drug. This route of use created difficult decisions regarding clinical monitoring in these patients. OBJECTIVES: To determine if prolonged observation is required after insufflation of bupropion and to further describe effects from this route of use. METHODS: This is a retrospective observational study reviewing all the cases of insufflated bupropion use reported to a single poison center without any other coingestants. RESULTS: The majority (85.7%) of patients had mild or moderate effects, and seizures occurred in 19.6% of cases; and the vast majority of patients were symptomatic by the time of the initial call to the poison center. We did not encounter any delayed effects after this route of use. CONCLUSIONS: This report describes the clinical effects reported, and the timing of these effects, after insufflation of bupropion.

A Fatal Colchicine Ingestion With Antemortem Blood Concentration.

ABSTRACT: Although there are multiple therapeutic uses for colchicine, it is particularly dangerous in the setting of overdose due to an irreversible mechanism of action combined with a narrow therapeutic window. Colchicine is an antimitotic agent that binds tubulin and inhibits microtubule polymerization. This produces a predictable sequence of toxicity beginning with gastrointestinal effects with progression to multiorgan system dysfunction. Unfortunately, there are no specific antidotes for colchicine toxicity after organ injury has occurred, which can lead to tragic consequences. Despite the recognized toxicity, it is exceedingly rare to find a case in the medical literature with a confirmed time of ingestion, amount ingested, data from longitudinal examinations, and laboratory assessments, with a quantitative blood colchicine concentration. We present a case of acute colchicine overdose of 18 mg (approximately 0.25 mg/kg) with subsequent multiorgan failure and death with an antemortem blood colchicine concentration of 14 ng/mL at 18.5 hours after ingestion.

Clinical effects of intravenous bupropion misuse reported to a regional poison center.

Bupropion is an antidepressant medication with expanding indications including smoking cessation, weight loss, attention-deficit/hyperactivity disorder, seasonal affective disorder, and amphetamine dependence. Despite its increasing popularity among providers, it has a well-known narrow therapeutic window which can lead to delayed onset of symptoms with extended-release formulations and devastating consequences in overdose. We have noticed some patients misusing bupropion via intravenous use and had difficulty guiding decisions regarding clinical monitoring in these patients. As this route entirely changes the kinetics of bupropion, this has caused concern within our group. We reviewed all the cases of intravenous bupropion use reported to a single poison center without any other coingestants. The majority (66.7%) of patients had moderate effects and one patient had a seizure. No deaths were reported. All patients were symptomatic by the time of initial call to the poison center if they had any reported symptoms due to bupropion. This case series describes the clinical effects reported, and the timing of these effects, after intravenous bupropion use.

Development of severe serotonin syndrome from acute ingestion of vilazodone without co-ingestion.

Vilazodone is a selective serotonin reuptake inhibitor (SSRI) that was introduced to the market in 2011. It has a novel mechanism combining serotonin reuptake and partial agonism of 5HT-1 receptors. It has gained popularity in treating first generation SSRI-resistant depression. There has been little description in the literature of adult overdose. We are describing a 21-year-old female with an intentional overdose of 400 mg of vilazodone. This patient progressively developed worsening serotonin syndrome, which was resistant to aggressive benzodiazepine administration. The patient required sedation with propofol and phenobarbital to control serotonin syndrome. Patient required continued sedation for 36 h post-ingestion, with subsequent extubation and return to normal mental status. We detail an atypical case of a novel SSRI overdose with the treatment regimen used.

Phenibut exposures and clinical effects reported to a regional poison center.

BACKGROUND: Phenibut is a synthetically produced central nervous system (CNS) depressant that is structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Phenibut has been identified as a drug of abuse with numerous clinical effects in overdose and a withdrawal syndrome with chronic use. The purpose of this study is to report the incidence of exposure calls regarding phenibut to a poison center, describe the reasons for its use and clinical effects. METHODS: Study subjects were identified using Toxicall®, the electronic medical record utilized by the Minnesota Poison Control System. All phenibut exposure calls from January 2000 through December 2018 were included. Analysis was performed on incidence of exposure calls, reported reasons for use, signs and symptoms, coingestants, and outcome. RESULTS: There were 56 exposure calls over 19 years with 48 (85.7%) calls within the past five years. Over 50% of patients had CNS effects and 10.7% had withdrawal concerns. Twenty-seven patients (48%) had abuse as the reason for use and 13 (23%) used phenibut to treat anxiety. There were documented coingestants in 35.7% of patients. No patients died due to reported phenibut use, though 11 patients (19.6%) were intubated. CONCLUSION: Exposure calls to a regional poison center regarding phenibut have increased over the past five years. CNS depression was common, and associated with significant clinical outcomes including respiratory failure requiring intubation. As phenibut is easily attainable and exposures appear to be increasing, physicians should be aware of phenibut-associated CNS and respiratory depression and be prepared to manage airways appropriately.

Hemodialysis in metformin-associated lactic acidosis due to acute overdose in a metformin-naïve patient.

Metformin is a common and generally well-tolerated medication in the treatment of diabetes but rarely has been implicated as the cause for metformin-associated lactate acidosis. This is usually caused by decreased elimination from renal dysfunction but is rarely described after an acute ingestion. We present a case of an acute intentional overdose of metformin in a metformin-naïve patient without renal dysfunction. The patient gradually developed altered mental status, tachypnea, hypotension, hyperglycemia, hypoglycemia, hypothermia, and vasoplegic shock unresponsive to vasopressor support. Despite attempts at alkalinization, the patient developed a lactic acidosis with a pH of 6.9 and lactate of 33 mmol/L. Hemodialysis was performed with rapid improvement of clinical status. This case provides a clinical context in the acute setting and illustrates the rare need for extracorporeal support in this setting, which may be lifesaving.

The association of hemodialysis and survival in intubated salicylate-poisoned patients.

INTRODUCTION: Salicylate poisonings are common due to their multiple uses and wide availability. The variation of presenting symptoms contributes to inconsistent treatments in the emergency department. Patients with severe salicylate overdose require a high minute ventilation. Early in the course of an overdose, a patient will require hyperventilation. If they become too fatigued to compensate, mechanical ventilation may be needed. It can be impossible to recreate such a high minute ventilation with mechanical ventilation. This places patients at a high risk for decompensation and death. Hemodialysis is an effective elimination technique for salicylate overdose and should be considered early. METHODS: All salicylate cases reported to the Illinois Poison Center were reviewed from 2003-2014. All intubated patients with a salicylate level >50mg/dl were included for analysis. Survival was compared to measured serum salicylate level and the administration of hemodialysis. RESULTS: 56 Cases were identified with an overall survival rate of 73.2% in patients with a serum salicylate level >50mg/dl. When patients did not receive hemodialysis, a peak salicylate level >50mg/dl had a 56% survival rate and 0% survival when the level was >80mg/dl. In the patients who received hemodialysis, a peak salicylate level >50mg/dl had a 83.9% survival rate and 83.3% survival when the level was >80mg/dl. CONCLUSION: Survival was decreased in these patients if hemodialysis was not performed. Mortality increases with the measured serum salicylate level. Timely hemodialysis for intubated salicylate overdose patients decreases mortality.

Chondrogenic progenitor cells respond to cartilage injury.

OBJECTIVE: Hypocellularity resulting from chondrocyte death in the aftermath of mechanical injury is thought to contribute to posttraumatic osteoarthritis. However, we observed that nonviable areas in cartilage injured by blunt impact were repopulated within 7-14 days by cells that appeared to migrate from the surrounding matrix. The aim of this study was to assess our hypothesis that the migrating cell population included chondrogenic progenitor cells that were drawn to injured cartilage by alarmins. METHODS: Osteochondral explants obtained from mature cattle were injured by blunt impact or scratching, resulting in localized chondrocyte death. Injured sites were serially imaged by confocal microscopy, and migrating cells were evaluated for chondrogenic progenitor characteristics. Chemotaxis assays were used to measure the responses to chemokines, injury-conditioned medium, dead cell debris, and high mobility group box chromosomal protein 1 (HMGB-1). RESULTS: Migrating cells were highly clonogenic and multipotent and expressed markers associated with chondrogenic progenitor cells. Compared with chondrocytes, these cells overexpressed genes involved in proliferation and migration and underexpressed cartilage matrix genes. They were more active than chondrocytes in chemotaxis assays and responded to cell lysates, conditioned medium, and HMGB-1. Glycyrrhizin, a chelator of HMGB-1 and a blocking antibody to receptor for advanced glycation end products (RAGE), inhibited responses to cell debris and conditioned medium and reduced the numbers of migrating cells on injured explants. CONCLUSION: Injuries that caused chondrocyte death stimulated the emergence and homing of chondrogenic progenitor cells, in part via HMGB-1 release and RAGE-mediated chemotaxis. Their repopulation of the matrix could promote the repair of chondral damage that might otherwise contribute to progressive cartilage loss.

Laryngeal hypersensitivity in the World Trade Center-exposed population: the role for respiratory retraining.

Upper airway symptoms among responders to the terrorist attack on 9/11 are progressive and multifactorial. For those symptoms that are laryngeal in origin, we are using a multidisciplinary approach that includes respiratory retraining and laryngeal desensitization through a speech pathologist trained in airway disorders. Our treatment paradigm and laryngeal hypersensitivity are discussed in this essay.

Tacrolimus Drug-Drug Interaction with Nirmatrelvir/Ritonavir (Paxlovid™) Managed with Phenytoin.

INTRODUCTION: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) pandemic has had a significant impact on communities and health systems. The Federal Drug Administration (FDA) authorized Pfizer's nirmatrelvir/ritonavir (Paxlovid™) through an EUA for the treatment of mild to moderate cases of COVID-19 at high risk for progression to severe disease. Patients with a history of transplant who test positive for COVID-19 are considered high risk because of their immunosuppression and are therefore candidates for nirmatrelvir/ritonavir. CASE REPORT: This is a case of a 67-year-old female with a past medical history of orthotopic heart transplant who received tacrolimus as part of her immunosuppressive regimen. She originally presented with complaints of dyspnea and cough for several days in the setting of COVID-19. The patient was started on nirmatrelvir/ritonavir due to her high risk for progression to severe disease. Four days after starting nirmatrelvir/ritonavir, she presented to the ED for slowed speech, fatigue, weakness, and loss of appetite. Upon admission she was found to have a supratherapeutic tacrolimus level of 176.4 ng/mL and an acute kidney injury. In this case, phenytoin was used as a CYP3A4 inducer to quickly decrease the tacrolimus level to within therapeutic range. CONCLUSION: This case highlights the strong and important drug-drug interaction between tacrolimus and nirmatrelvir/ritonavir leading to toxic levels of tacrolimus. It also demonstrates the utility and effectiveness of phenytoin as a "rescue" medication for tacrolimus toxicity.

The impact of fellowship-trained medical toxicology faculty on emergency medicine resident in-training examination scores.

Background: The American Board of Emergency Medicine (ABEM) In Training Exam (ITE) gauges residents' medical knowledge and has been shown to correlate with subsequent performance on the ABEM board qualifying examination. It is common for emergency medicine (EM) residencies to employ subspecialty-trained faculty members with the expectation of improved resident education and subspecialty knowledge. We hypothesized that the presence of subspecialty faculty in toxicology would increase residents' scores on the toxicology portion of the ITE. Methods: We assessed ABEM ITE scores at our institution from 2013-2022 and compared these to national data. The exposure of interest was the absence or presence of fellowship-trained toxicology faculty. The primary outcome was performance on the toxicology portion of the ITE, and secondary outcome was overall performance on the exam. Results: Residents who had ≥1 toxicology faculty were 37% (95% CI: 1.01-1.87) more likely to surpass the national average for toxicology scores, and those who had ≥2 toxicology faculty were 77% (95% CI: 1.28-2.44) more likely to surpass the national average for toxicology scores on the ABEM ITE. With the presence of ≥2 toxicology faculty, there was also an increase in toxicology score by years in training, with residents being 63% (95% CI: 1.01-2.64), 68% (95% CI: 1.08-2.61), and 92% (95% CI: 1.01-3.63) more likely to surpass the national average for toxicology score in first, second, and third years of residency, respectively. There was no significant relationship between the presence of toxicology faculty and the overall ABEM ITE scores. Conclusions: The presence of fellowship-trained toxicology faculty positively impacted residents' performance on the toxicology portion of the ABEM ITE but did not significantly impact the overall score. With the presence of ≥2 toxicology faculty we noted an improvement in toxicology scores throughout the 3 years of training, indicating that an individual rotation or educational block is probably less important than spaced repetition through a longitudinal curriculum.

Applying Project ECHO (Extension for Community Health Care Outcomes) to improve addiction care in rural emergency departments.

Background: Advancements in research and legislation have improved emergency provider ability to treat opioid use disorder (OUD), but dissemination into rural emergency departments (EDs) is limited. Project Extension for Community Healthcare Outcomes (ECHO) allows community generalists to learn from specialists through telementoring. We aimed to use ECHO to facilitate knowledge translation, increase confidence, and change behavior of rural ED providers treating patients with OUD. Methods: Stakeholder interviews were conducted with rural ED providers. A group of ED addiction experts created an ECHO curriculum with eight OUD topics. ED health professionals were recruited and completed pre/post surveys centered around knowledge and comfort with treating OUD in the ED, with focus on clinical practice and stigma. Following the ECHO model, sessions included a 20-min didactic followed by two cases presented by participants, with discussion facilitated by faculty. Results: Twenty-seven participants registered; seven attended ≥75% of sessions and completed both surveys. Of the seven, three were physicians, two advanced practice providers, one nurse, and one clinical pharmacist. Eight 1-hour sessions were conducted in two cohorts between January and December 2021. On a 5-point Likert scale, respondents on average agreed with questions evaluating acceptability (mean ± SD 3.96 ± 0.64), appropriateness (mean ± SD 4.18 ± 1.18), and feasibility (mean ± SD 4.00 ± 1.17). Participants had a 1.09-point increase (paired t-test = 2.43, p = 0.05) on 7-point Likert-scale questions measuring self-efficacy and a 0.13-point change (paired t-test = 2.64, p = 0.04) on 4-point Likert scale questions measuring stigmatizing attitudes (reduction of attitudes). A total of 71% (5/7) reported changes in clinical practice and 57% (4/7) in departmental protocols after participation. Conclusions: Our ED OUD ECHO course successfully created a model for rural ED providers to learn from ED addiction experts. It was well received and impacted self-reported provider stigmatizing attitudes, patient-facing behavior, and departmental initiatives. Recruitment was challenging and participation was limited. Future efforts will target maximizing recruitment.

E-Cigarette, or Vaping, Product Use Associated Lung Injury (EVALI) with Acute Respiratory Failure in Three Adolescent Patients: a Clinical Timeline, Treatment, and Product Analysis.

INTRODUCTION: E-cigarette, or vaping, product use associated lung injury (EVALI) has become a recent concern among public health officials. Factors that contribute to the concern include an increasing number of cases over time, the severity of the illness, and an unknown understanding of the pathophysiology and etiology of the illness. CASE SERIES: We cared for three adolescent patients with acute respiratory failure secondary to EVALI. All three patients were treated with high-dose steroids in addition to antimicrobials, which resulted in clinical improvement and resolution of their respiratory failure. Pulmonary function testing was performed on these previously healthy patients both acutely and subacutely. Additionally, we report the results from the laboratory analysis of one vaping device fluid which revealed previously unpublished components within these products. DISCUSSION: EVALI is a recent public health concern without a known etiology which can cause life-threatening lung injury in patients without prior lung pathology. We hope these cases will highlight the importance of return precautions in adolescents with vague respiratory symptoms and provide a cautionary tale to providers while they counsel patients regarding the use of these products.

Long-term Voice Outcome Following Radiation Versus Laser Microsurgery in Early Glottic Cancer.

OBJECTIVES: Long-term voice outcome (LTVO) after radiation (XRT) or trans-oral laser microsurgery (TLM) is unclear. This study is a multi-modality analysis of LTVO following XRT or TLM in patients with early glottic cancer. We hypothesize that as compared with TLM, LTVO is worse in the XRT group because of progressive fibrosis in the glottic tissue MATERIAL AND METHODS: One hundred and two patients with early glottic carcinoma (carcinoma in situ, T1, T2) were included. Multi-modality voice analyses were performed with self-perception using Voice Handicap Index-10, objective analysis using Analysis of Dysphonia in Speech and Voice Software (Cepstral Spectral Index of Dysphonia score for Consensus Auditory-Perceptual Evaluation of Voice sentences), and perceptual rating by two blinded speech language pathologists (GRBAS scale). RESULTS: Fifty-five patients received TLM (mean follow-up = 52 months) and 47 patients had XRT (mean follow-up = 65 months). There is no difference between the two groups in sex, age, stage, and follow-up time. Intraclass correlation coefficient between raters was high at 0.94. Controlling for age and stage, XRT increases total GRBAS score by 1.38 points (P = 0.006) and increases Cepstral Spectral Index of Dysphonia score by 13.7 points (P < 0.001) when compared with the TLM group. No significant differences were found in the Voice Handicap Index score between the XRT and the TLM groups. CONCLUSIONS: This is the first multi-modality voice analysis to suggest TLM results in better LTVO than XRT in GRBAS score and objective voice analysis but not in self-perception. These differences may reflect the progressive effects of XRT on glottic tissue. A randomized controlled study is required to confirm our findings.