Acute exposure to hydrazine reported to four United States regional poison centers: reconsidering a paradigm.

INTRODUCTION: Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have been taken due to concern for severe toxicity. This study seeks to better understand manifestations of acute occupational exposures to hydrazine to guide recommendations for management. MATERIALS AND METHODS: A retrospective database review of records from four United States regional poison centers was conducted of all human exposures to hydrazine, monomethylhydrazine, or 1,1-dimethylhydrazine over two decades. Following case abstraction, descriptive statistics were performed to characterize demographics, manifestations, treatments, and outcomes. RESULTS: One hundred and thirty-five cases were identified, and most were adult males exposed to inhaled hydrazine propellant vapors. Fifty-seven percent of patients were asymptomatic following exposure; otherwise, common symptoms were dyspnea, throat irritation, cough, ocular irritation, and headache. All patients were evacuated or received decontamination, with a few reports of symptomatic treatments, including oxygen supplementation and salbutamol (albuterol). Patients usually recovered quickly and were released after a brief healthcare facility evaluation or observed locally. No patients developed delayed symptoms. Symptoms of severe toxicity were not observed, and there were no deaths. DISCUSSION: Acute exposures to hydrazines during operations within the aerospace industry appear to be limited primarily to mucosal and mild pulmonary irritation without significant neurologic, hepatic, or hematologic toxicity. These findings are contrary to previously established expectations and may be related to low-level exposures or possibly due to current emergency countermeasures. CONCLUSIONS: Care in occupational hydrazine exposure will focus on evacuation, decontamination, and symptomatic management of chemical irritant properties of hydrazines. It is reasonable to manage mild cases outside of a healthcare facility. Continued endeavors in human space exploration and habitation will increase the risk of these exposures, making it imperative that clinicians be comfortable with the care and management of these patients.

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.

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.

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.

Initial Experience with F(ab')2 Antivenom Compared with Fab Antivenom for Rattlesnake Envenomations Reported to a single poison center during 2019.

BACKGROUND: There are two Food and Drug Administration (FDA)-approved antivenoms available for rattlesnake envenomations in the United States: the equine-derived F (ab')2 product sold with the brand name Anavip (F (ab')2 AV) and the ovine-derived Fab product sold with the brand name Crofab (FabAV). OBJECTIVE: To compare the clinical outcomes of rattlesnake envenomation patients treated either with FabAV or F (ab')2AV or a combination of these. METHODS: This is a retrospective chart review of all human rattlesnake envenomations requiring antivenom reported to one regional poison control center in 2019. Patients were categorized as receiving F (ab')2 AV, FabAV, or a combination of both. Baseline characteristics included demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation. RESULTS: There were a total of 123 patients requiring antivenom. Of these, 57 (46.3%) received FabAV, 53 (43.1%) received F (ab')2 AV, and 13 (10.6%) received a combination of these. Those receiving F (ab')2 AV were younger, with an average age of 40.8 (±25.0) years versus 51.3 (±19.9) years (p = 0.0161) for those receiving FabAV. Time between envenomation and antivenom administration, ASSS, and the percentage of those with coagulopathy at presentation were otherwise similar. Patients treated with F (ab')2 AV or FabAV received a similar total number of vials [16.0 vials (±6.1) vs 14.5 vials (±5.4), p = 0.189], but patients treated with F (ab')2 AV were more frequently given additional doses [31 patients (58.5%) vs. 22 FabAV patients (38.6%), p = 0.0051]. In patients with outpatient follow-up for 2 weeks, fewer patients treated with F (ab')2 AV developed late coagulopathy [5 patients (11.1%) vs 22 FabAV patients (48.9%), p = 0.0004]. Adverse events were generally mild and uncommon with no difference in frequency between patients who received either antivenom (2 F (ab')2 AV patients vs 4 FabAV patients, p = 0.6637). CONCLUSIONS: Other than patient age, we found no significant difference in the baseline demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation between patients receiving F (ab')2 AV or FabAV. Patients receiving F (ab')2 AV were more likely to be given an additional dose beyond the minimum typical treatment course, but less likely to develop late coagulopathy. Adverse events were uncommon and generally mild whether patients received either antivenom.

Comparison of two guideline-concordant antimicrobial combinations in elderly patients hospitalized with severe community-acquired pneumonia.

OBJECTIVE: Two of the guideline-concordant therapies for severe community-acquired pneumonia are either a beta-lactam and fluoroquinolone or beta-lactam and macrolide. However it is unclear if there is a benefit for one vs. the other for elderly patients with severe community-acquired pneumonia. DESIGN: A retrospective population-based cohort study of patients with community-acquired pneumonia. SETTING: Patients admitted to an intensive care unit of any Department of Veterans Affairs hospital during 5-yr period. PATIENTS: We included only those patients>65 yrs of age admitted to the intensive care unit with community-acquired pneumonia who received either beta-lactam+fluoroquinolone or beta-lactam+macrolide antibiotic therapy for pneumonia. INTERVENTION: Not applicable. MEASUREMENTS: We used multilevel regression models to examine the effect of beta-lactam+fluoroquinolone vs. beta-lactam+macrolide on each of the outcomes after adjusting for potential confounders using propensity scores. MAIN RESULTS: The cohort consisted of 1,989 patients: 98.5% male and a mean age of 74 yrs. For treatment, 44% of subjects received beta-lactam+fluoroquinolone and 56% received beta-lactam+macrolide. Unadjusted 30-day mortality was 27% for beta-lactam+fluoroquinolone and 24% for beta-lactam+macrolide (p=.11). In the multilevel models, the use of beta-lactam+fluoroquinolone was not significantly associated with 30-day mortality (odds ratio 1.05, 95% confidence interval 0.85-1.30). However, the use of beta-lactam+fluoroquinolone was significantly associated with increased mean length of stay (incidence rate ratio 1.30, 95% confidence interval 1.27-1.33). CONCLUSIONS: We found no significant difference for 30-day mortality but did demonstrate an association with increase in length of stay associated with the use of beta-lactam + fluoroquinolone. Randomized controlled trials are needed to determine the most effective antibiotics regimes for patients with severe pneumonia.