Chlorfenapyr poisoning: a systematic review.

INTRODUCTION: Chlorfenapyr, a N-substituted halogenated pyrrole, is a broad-spectrum insecticide. The insecticidal activity of chlorfenapyr depends on its biotransformation by hepatic cytochrome P450 monooxygenases to tralopyril, which uncouples mitochondrial oxidative phosphorylation and disrupts adenosine triphosphate production. Neither the metabolism of chlorfenapyr nor the mechanism of tralopyril is completely elucidated. Acute human chlorfenapyr poisoning is not well characterized, and best practice in management following acute exposure is unclear. The purpose of this review is to characterize acute human chlorfenapyr poisoning by its clinical course, laboratory investigations, and imaging findings and propose a management plan for acute human chlorfenapyr exposure. METHODS: We systematically searched PubMed, Web of Science, Google Scholar, and EMBASE from inception to April 2024 across all languages for human chlorfenapyr and tralopyril cases, with descriptions of exposure, clinical manifestations, and clinical course included. Only manuscripts and abstracts from scientific conferences with sufficient clinical data following acute human exposures were included. In vitro studies, animal studies, agricultural studies, environmental impact studies, and non-clinical human studies were excluded. We then reviewed citations of included studies for additional eligible publications. Non-English publications were translated using Google Translate or primarily translated by our authors. The study adhered to Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. RESULTS: We identified 3,376 publications of which 48 met study inclusion criteria, describing 75 unique cases of human poisoning from ingestion, inhalation, dermal exposure, and intra-abdominal injection of chlorfenapyr. No cases of tralopyril exposure were identified. The median time from exposure to symptom onset was six hours (interquartile range 1-48 hours). The most frequent initial or presenting signs/symptoms included diaphoresis, nausea and/or vomiting, and altered mental status. While hyperthermia (≥38 degrees centigrade) was less common at presentation, hyperthermia developed in 61 percent of all patients and was temporally associated with clinical deterioration and death. Most common laboratory abnormalities included elevated blood creatine kinase activity, hepatic aminotransferase activities, and lactate concentration. Imaging studies of the central nervous system often showed extensive symmetrical white matter abnormalities with swelling. Case fatality was 76 percent, and survivors commonly experienced sustained neurological sequelae. Management strategies were highly varied, and the effectiveness of specific medical interventions was unclear. DISCUSSION: Acute human chlorfenapyr poisoning is characterized by a latent period as long as 14 days, deterioration over hours to days, and can result in serious morbidity and mortality. Development of hyperthermia, likely driven by oxidative phosphorylation uncoupling by tralopyril, is an ominous clinical sign and is temporally associated with clinical decompensation and death. Laboratory abnormalities, particularly elevated creatine kinase activity, hepatic aminotransferase activities, and lactate concentration, were common, but only creatine kinase activity differed amongst survivors and fatalities. Best clinical practice in the management of patients exposed to chlorfenapyr is unclear, and we opine that a conservative approach with close clinical monitoring and supportive care is prudent. LIMITATIONS: The limitations of all reviews include their inherent retrospective and observational nature as well as publication bias that emphasizes severe outcomes, thus impacting the spectrum of illness and skewing mortality percentage. In addition, we interrogated a finite number of databases for publications on human chlorfenapyr exposure and there were limited cases with laboratory testing to confirm chlorfenapyr poisoning. Analysis of our systematic review was not powered to detect differences between groups, comparative statistics were not performed, and significance is not reported. CONCLUSIONS: Acute human chlorfenapyr toxicity is characterized by a latent period following exposure, development of new or progression of established signs/symptoms, potential for critical illness, rapid deterioration, serious morbidity, and mortality. A conservative approach to patient management is prudent.

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.

Spaceflight Recovery Considerations for Acute Inhalational Exposure to Hydrazines.

INTRODUCTION: Inhalation of hydrazine or hydrazine-derivative (for example, monomethylhydrazine) vapors during spaceflight operations remains a risk to crew and ground support personnel. Here we sought to provide an evidence-based approach to inform acute clinical treatment guidelines for inhalational exposures during a noncatastrophic contingency spaceflight recovery scenario.METHODS: A review of published literature was conducted concerning hydrazine/hydrazine-derivative exposure and clinical sequelae. Priority was given to studies that described inhalation though studies of alternative routes of exposure were additionally reviewed. Where possible, human clinical presentations were prioritized over animal studies.RESULTS: Rare human case reports of inhalational exposure and multiple animal studies provide evidence of varied clinical sequelae, including mucosal irritation, respiratory concerns, neurotoxicity, hepatotoxicity, hemotoxicity (including Heinz body development and methemoglobinemia), and longitudinal risks. In an acute timeframe (minutes to hours), clinical sequelae are likely to be limited to mucosal and respiratory risk; neurological, hepatotoxic, and hemotoxic sequelae are unlikely without recurrent, longitudinal, or noninhalational exposure.CONCLUSIONS: Acute clinical management should focus on likely clinical concerns as supported by existing data; recovery medical personnel should be prepared to manage mucosal irritation and respiratory concerns, including the potential need for advanced airway management. There is little evidence supporting the need for acute interventions for neurotoxicity and there is no evidence that acute hemotoxic sequelae would drive the need for on-scene management of methemoglobinemia, Heinz body development, or hemolytic anemia. Training that overemphasizes neurotoxic or hemotoxic sequelae or specific treatments for such conditions potentially raises the risk for inappropriate treatment or operational fixation.Hanshaw BC, Ryder VE, Johansen BD, Pattarini JM, Nguyen HN, Nowadly CD, Blue RS. Spaceflight recovery considerations for acute inhalational exposure to hydrazines. Aerosp Med Hum Perform. 2023; 94(7):532-543.

Failure of Risk Assessment After Paracetamol Overdose-A Short Communication.

BACKGROUND: The accepted treatment for patients with acetaminophen/paracetamol overdose includes risk assessment based on the Rumack-Matthew (R-M) nomogram. An inaccurate use of the nomogram may result in improper treatment. Clinicians were surveyed to determine their understanding and proper use of this risk assessment tool in practice. METHODS: Differences between visual risk assessment using the same depiction of the R-M nomogram and calculated risk assessment were determined using an online calculator developed based on the Rumack equation. An online survey was administered in French between August 25, 2021, and November 25, 2021, as a Google Form with 14 questions (the paracetamol concentration and time postingestion were stated). A total of 147 respondents with an average age of 32 years (range 23-61 years) performed risk assessment (low/possible/probable/not assessable). The mean assessment accuracy was 66.2 ± 26.7% (12.3-99.3). The sensitivity, specificity, positive predictive value, and negative predictive value were 93%, 55%, 71%, and 89%, respectively. A subcohort of n = 31 senior clinicians showed the same trends (91%, 52%, 69%, and 84%). RESULTS: Approximately 7% of patients who are at risk of hepatotoxicity based on the R-M nomogram would not be treated. By contrast, N-acetylcysteine was not recommended by the R-M nomogram but would be administered to approximately 50% of patients. A concern for the latter group is that anaphylactoid reactions occur in up to 25% of patients with low paracetamol concentrations. CONCLUSIONS: Some patients may be undertreated, resulting in possible hepatotoxicity, and many patients may be overtreated, resulting in a high percentage of anaphylaxis. Rather than relying on visual risk assessment, physicians should use an online calculator ( www.hopitox.com/?lang=en ) or consult with a toxicologist or poison center to substantially improve patient care after acetaminophen/paracetamol overdose.

The Toxicology Investigators Consortium Case Registry-the 2021 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure.

The Toxicity, Pathophysiology, and Treatment of Acute Hydrazine Propellant Exposure: A Systematic Review.

INTRODUCTION: Hydrazines are highly toxic inorganic liquids that are used as propellants in military and aviation industries, such as the U.S. Air Force F-16 Emergency Power Unit and SpaceX SuperDraco Rockets. The most commonly used derivatives include hydrazine, monomethylhydrazine, and 1,1-dimethylhydrazine (unsymmetrical dimethylhydrazine). Industrial workers in close contact with hydrazines during routine maintenance tasks can be exposed to levels well above the National Institute for Occupational Safety and Health relative exposure limits. MATERIALS AND METHODS: A systematic review was performed using PubMed, Web of Science, Google Scholar, National Aeronautics and Space Administration Technical Server, and Defense Technical Information Center, and data related to hydrazine exposures were searched from inception to April 2020. Publications or reports addressing hydrazine toxicity, pathophysiology, and treatment of hydrazine fuel exposure were selected. RESULTS: Acute toxic exposures to hydrazine and its derivatives are rare. There are few case reports of acute toxic exposure in humans, and data are largely based on animal studies. The initial search identified 741 articles, manuscripts, and government reports. After screening for eligibility, 51 were included in this review. Eight articles reported acute exposures to hydrazine propellant in humans, and an additional 14 articles reported relevant animal data. CONCLUSIONS: Exposure to small amounts of hydrazine and its derivatives can cause significant soft tissue injury, pulmonary injury, seizures, coma, and death. Neurologic presentations can vary based on exposure compound and dose. Decontamination is critical as treatment is mainly supportive. High-dose intravenous pyridoxine has been suggested as treatment for hydrazine-related neurologic toxicity, but this recommendation is based on limited human data. Despite recent research efforts to generate less toxic alternatives to hydrazine fuel, it will likely continue to have a role in military and aviation industries. Aerospace and military physicians should be aware of the toxicity associated with hydrazine exposure and be prepared to treat hydrazine toxicity in at-risk populations.

Acute and Chronic Carbon Monoxide Toxicity from Tobacco Smoking.

INTRODUCTION: Carbon monoxide (CO) is produced from incomplete combustion of hydrocarbons and is a by-product of tobacco smoking. Chronic cigarette smokers often have carboxyhemoglobin (COHb) concentrations as high as 10%. We report a case of severely elevated COHb and polycythemia because of tobacco smoking and provide a review of the literature regarding elevated COHb in smokers. MATERIALS AND METHODS: A comprehensive search of PubMed and Google Scholar was performed looking for articles on tobacco smoking and CO, COHb, CO poisoning, cigarettes, pipes, cigars and water pipes/hookah smokers. RESULT: COHb levels in frequent cigarette smokers generally range from 4.2% presmoking to 8.6% postsmoking. A heavy cigarette smoker presented twice with symptoms of CO toxicity and was found to have levels 21.8 to 24.2%. Cigar smokers have been found to have COHb ranging as high as 13.0 to 38.6% in case reports. Waterpipe or "hookah" smokers generally have COHb levels 10.1% +/-2.5% and case reports, and series of even higher levels associated with CO toxicity symptoms are common. Waterpipe smokers have been found to have COHb levels as high as 39.2% after smoking. CONCLUSIONS: Many active duty military and military veterans are tobacco smokers and these patients and their health care providers should be aware of the adverse effects of CO toxicity from tobacco smoking. Patients may have symptoms such as headaches, syncope, and ataxia in the setting of acute CO toxicity; however, the chronic effects of CO may not be completely understood. Future work could explore chronic CO toxicity and its effects on strength and exercise tolerance in military personnel and provide education to service members, veterans, and health care providers.

Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization.

PURPOSE: To noninvasively image retinal pericytes in the living eye and characterize NG2-positive cell topography and morphology in the adult mouse retina. METHODS: Transgenic mice expressing fluorescent pericytes (NG2, DsRed) were imaged using a two-channel, adaptive optics scanning laser ophthalmoscope (AOSLO). One channel imaged vascular perfusion with near infrared light. A second channel simultaneously imaged fluorescent retinal pericytes. Mice were also imaged using wide-field ophthalmoscopy. To confirm in vivo imaging, five eyes were enucleated and imaged in flat mount with conventional fluorescent microscopy. Cell topography was quantified relative to the optic disc. RESULTS: We observed strong DsRed fluorescence from NG2-positive cells. AOSLO revealed fluorescent vascular mural cells enveloping all vessels in the living retina. Cells were stellate on larger venules, and showed banded morphology on arterioles. NG2-positive cells indicative of pericytes were found on the smallest capillaries of the retinal circulation. Wide-field SLO enabled quick assessment of NG2-positive distribution, but provided insufficient resolution for cell counts. Ex vivo microscopy showed relatively even topography of NG2-positive capillary pericytes at eccentricities more than 0.3 mm from the optic disc (515 ± 94 cells/mm(2) of retinal area). CONCLUSIONS: We provide the first high-resolution images of retinal pericytes in the living animal. Subcellular resolution enabled morphological identification of NG2-positive cells on capillaries showing classic features and topography of retinal pericytes. This report provides foundational basis for future studies that will track and quantify pericyte topography, morphology, and function in the living retina over time, especially in the progression of microvascular disease.

Anterior exposure of the spine for removal of lumbar interbody devices and implants.

STUDY DESIGN: A retrospective review of a consecutive series of 14 patients operated on between March 1998 and April 2005. OBJECTIVES: To report on patients having undergone revision lumbar surgery anteriorly to remove interbody devices placed anteriorly or posteriorly and to determine the incidence of associated complications. SUMMARY OF BACKGROUND DATA: The popularity of interbody lumbar surgery has grown in recent years. Consequently, the number of anterior revision procedures has increased. The risks associated with anterior approach for revision procedures and interbody device removal, in particular, have not been reported. METHODS: The results of 13 consecutive patients who had removal of interbody devices through an anterior approach and 1 patient with removal of anterior fixation (7 males, 7 females; mean age 43 years) were reviewed. The procedure during which the original implant was placed was a posterior lumbar interbody fusion in 4, transforaminal lumbar interbody fusion in 5, and anterior lumbar interbody fusion in 5 patients. Four attending spine surgeons performed the procedures with the assistance of 4 experienced access surgeons. RESULTS: Ten of 14 (71%) patients had complications associated with anterior exposure of revision surgery. Vascular injury is the most common complication (57%). Vascular complications occurred in 100% (4/4) of the revisions of previous posterior lumbar interbody fusions and 80% (4/5) of previous anterior lumbar interbody fusions. The complication rate at L4-5 and L5-S1 was 89% and 40%, respectively. There was 1 postoperative mortality. CONCLUSIONS: Anterior removal of lumbar interbody devices placed anteriorly or posteriorly has a high incidence of complication. Average blood loss and hospital stay are increased with revision anterior surgery. The vascular complication rate is 2-fold higher at L4-L5 level compared to L5-S1.

Transforaminal lumbar interbody fusion: an independent assessment of outcomes in a difficult patient population.

BACKGROUND: Transforaminal lumbar interbody fusion is becoming increasingly popular for the surgical treatment of lumbar degenerative conditions. However, the outcomes following the procedure have only begun to be evaluated. MATERIAL/METHODS: The authors reviewed all patients previously treated by TLIF at our tertiary center with minimum two year follow-up. Between 1997 and 2001, twenty-seven patients underwent the procedure. They were evaluated clinically and radiographically at regular intervals for a minimum two years following surgery and longer term follow-up was carried out by telephone interview. Long-term follow-up was undertaken by an independent assessor (a spine surgeon not directly involved in the patient's care) and outcomes were assessed using the measure designed by Macnab/McCulloch/An. Follow-up averaged 30 months and ranged from 24 to 42 months. RESULTS: All but two patients obtained a solid radiographic arthrodesis and complications were few. However, only eleven patients obtained excellent or good clinical results, while 16 had fair or poor outcomes. CONCLUSIONS: TLIF is a technically demanding procedure which can be done with relatively few complications and offers excellent rates of arthrodesis. However, the outcomes of the procedure and indications for the procedure in difficult patient populations clearly require further study.

Osteoporotic vertebral burst fractures with neurologic compromise.

A retrospective study was performed on the operative results following osteoporotic burst fractures with neurologic compromise. We sought to investigate the results of operative decompression and stabilization in patients with neurologic deficit as a result of an osteoporotic burst fractures. We examined the postoperative radiographic outcomes, level of disability, functional outcomes, and complications. Compression fractures of the anterior vertebral column secondary to osteoporosis and minimal trauma are a common clinical entity. These fractures are often effectively treated by nonoperative means. However, compressive failure of the middle vertebral column can lead to retropulsion of vertebral body fragments with significant canal compromise and neurologic injury. Treatment of these more severe injuries becomes more difficult and is less well established. Functional outcomes and disability from pain have not been examined. Previous reports on this subject have documented generally good results but have given few specific data regarding outcomes. We retrospectively report on a series of 10 patients, from 1995 to 1998, with osteoporotic burst fractures, which led to varying degrees of neurologic compromise. There were nine female and one male patient with a mean age of 76 years. Nine of the 10 patients presented more than 1 month following the onset of neurologic symptoms; 70% of the fractures occurred at the thoracolumbar junction (T11-L2). Mean loss of anterior column height was 59%, with significant kyphosis (mean 28 degrees) in nine of the 10 fractures. Mean canal compromise was 41%. At presentation, seven patients were Frankel grade D and three were Frankel grade C. All patients were treated operatively with decompression and arthrodesis. Mean time to follow-up was 16 months. Six of the 10 patients had improvement of their Frankel grade postoperatively and one deteriorated neurologically. Seven of the eight surviving patients completed the Oswestry questionnaire with a mean score of 44%, representing severe disability secondary to low back pain. The Physical Component score of the SF-36 was at or below the national mean for each patient. Complications were present in six of the eight surviving patients. Osteoporotic fractures are not benign. Careful evaluation for neurologic deterioration is warranted. Neurologic recovery occurred in six of the 10 patients; however, significant disability secondary to pain was common.

Intermediate term follow-up of calcaneal osteotomy and flexor digitorum longus transfer for treatment of posterior tibial tendon dysfunction.

Twenty-three patients with stage II posterior tibial tendon dysfunction who had failed non-surgical therapy were treated with flexor digitorum longus transfer and calcaneal osteotomy. At latest follow-up averaging 35 +/- 7 months (range, 24 to 51 months), 22 patients (96%) were subjectively "better" or "much better." No patient had difficulty with shoe wear; however, four patients (17%) required routine orthotic use consisting of a molded shoe insert. AOFAS scores were available on 21 patients and improved from a preoperative mean of 50 +/- 14 (range, 27 to 85) to a postoperative mean of 89 +/- 10 (range, 70 to 100). Our experience, at an intermediate date follow-up is that calcaneal osteotomy and flexor digitorum longus transfer is a safe and effective form of treatment for stage II posterior tibial tendon dysfunction.