Fentanyl Deaths in Infants and Children: A Case Series and Literature Review.

ABSTRACT: Death due to fentanyl and its various analogs has resulted in an exponential rise in deaths throughout the United States, overwhelming many medical examiner offices for over a decade. Its potency and prevalence have caused fentanyl to become the most reported substance in overdose fatalities, with an accompanying increase in exposure of the most vulnerable, infants and children. This report provides information about fentanyl in the pediatric population, including case examples, proposed investigative practices, published therapeutic and lethal blood concentrations, and available resources for future cases. Nine cases of pediatric death between 2013 and 2023 due to fentanyl were reviewed. Five case summaries are presented that highlight classic features of fentanyl deaths in infants, children, and teenagers. Deaths due to fentanyl have continued to rise year after year. Infants and children, most of whom are opioid naive, are at ever increased risk for exposure to high levels of fentanyl. The legal ramifications of a positive fentanyl level in a child increase the need for caution on the part of the forensic pathologist. Understanding what can and cannot be proven by autopsy as well as what resources are available to strengthen one's justification for fentanyl being the primary cause of death is critical.

Sudden death after being in a bounce house: a late complication of congenital diaphragmatic hernia.

A 3-year-old white female with no significant past medical history was found unresponsive and apneic after several hours of vomiting. The patient had reportedly felt unwell since jumping in a bounce house at a festival earlier in the day. After one hour of attempted resuscitation by EMS and hospital staff, the patient was pronounced deceased. On autopsy there was a 3 cm opening in the left posterolateral hemidiaphragm with the spleen, the stomach, and portions of the small and large bowel displaced into the left chest cavity, resulting in compression of both lungs and the heart to the right side of the chest. The right lung weighed 295 g while the left lung weighed 73 g. Histologic examination revealed atelectasis in the left lung and congestion in the right lung, the spleen, the stomach, and the bowel. The cause of death was ultimately ruled to be respiratory compromise and associated gastrointestinal complications due to diaphragmatic herniation of abdominal contents into the chest cavity. It is hypothesized that herniation occurred in this case secondary to increased intra-abdominal pressure from jumping in a bounce house, an etiology that we were unable to find elsewhere despite a thorough literature search.

Spontaneous iliac vein rupture in the setting of a long dwelling intravenous vena cava filter.

Venous thromboembolism impacts as many as 600,000 individuals each year in the United States, leading to significant morbidity and mortality. While typically treated with anticoagulants, retrievable inferior vena cava (IVC) filters may also be used for acute prevention of pulmonary embolism. The FDA recommends removing IVC filters within 29-54 days because long dwelling filters are associated with serious complications from the filter itself, such as perforation of adjacent structures and filter fracture. We report an unusual case in which a patient had an inferior venous cava filter in place for two years before experiencing spontaneous rupture of the left iliac vein. There was no evidence of filter migration or inferior venous cava perforation. Spontaneous iliac vein ruptures are rare, with fewer than 50 reported cases, and are not typically seen with a long-dwelling IVC. This case describes a unique complication of retrievable filters and highlights the importance of retrieving filters as soon as the acute danger of pulmonary embolism has resolved.

A complicated case of bowel obstruction with sepsis and methamphetamine toxicity in a child with pica.

In this report, a pediatric case of bowel obstruction with sepsis complicated by methamphetamine toxicity is described. The decedent, an eleven-year-old female with a clinical history of pica, was found unresponsive in her home and pronounced dead following unsuccessful resuscitative efforts. Radiologic imaging showed multiple radio-opaque foreign objects in the stomach and bowel. Autopsy revealed a green leafy substance, coins and other metallic items, folded paper, and plastic in her stomach and bowels. Postmortem iliac blood and urine tested positive for amphetamine and methamphetamine. While the decedent's medical history and autopsy findings provided evidence consistent with bowel obstruction with sepsis due to the ingestion of foreign materials, the high methamphetamine concentration was suggestive of concurrent methamphetamine toxicity. Unique complications associated with this case include the phenomenon that methamphetamine toxicity and bowel obstruction can present similarly in children and the reported opinion that accidental drug ingestion is uncommon in children over the age of five. This case emphasizes that the age range for suspected accidental drug ingestion should be expanded for those with pica, as these patients, despite being older, may not be able to differentiate between what they should and should not ingest. Furthermore, when treating a pediatric patient with pica that appears to present with bowel obstruction, unintentional drug ingestion should also be considered, particularly if there is a suspicion that the child lives in a household where drugs are abused, given the prospect that drug toxicity can present similarly.

Involving a real patient in the design and implementation of case-based learning to engage learners.

Real patients offer unique opportunities to develop authentic, engaging, and transformative learning experiences for students. Patients are widely employed to teach clinical and interpersonal skills in the clerkship phase of their medical education (M3-M4), but have not been extensively included in the preclinical curriculum (M1-M2) when students are focused on acquiring foundational biomedical science knowledge. To maximize learning and help students connect foundational and clinical science concepts to real-world clinical problems, we involved a real patient in the creation and implementation of a case-based learning (CBL) activity in our preclinical curriculum. Using the patient's narrative as a framework, the CBL addressed relevant aspects of physiology, pathophysiology, anatomy, pharmacology, and nutrition, as well as clinical care decisions, health literacy, and medical ethics. The intervention was implemented with the 2019 and 2020 graduating medical school classes during the Gastrointestinal Systems course in the second year of our curriculum. The results of a survey revealed that, overall, a majority of the students agreed or strongly agreed that the activity increased engagement in class, increased the depth of discussion within their teams, increased the depth of discussion between teams, helped students to apply basic science concepts to the clinical material in the case, helped students better understand the disease processes described in the case, enhanced awareness of the complexity of patient care, provided an authentic learning experience, and elicited a feeling of empathy.

A case of cardiac tamponade due to an isolated abscess in the ascending aorta of a pregnant woman with a history of intravenous substance abuse.

We describe the case of a 23-year-old white female, 10-12 weeks pregnant, with a history of intravenous drug use and a recently diagnosed pneumonia, who was found deceased in her bed after a night of sleep. Although postmortem serum toxicology tested positive for alprazolam, tetrahydrocannabinol, and morphine, the ultimate cause of death was determined to be cardiac tamponade secondary to an isolated abscess in the ascending aorta. The patient had several risk factors for aortic rupture and cardiac tamponade including intravenous drug use, pneumonia, and pregnancy. However, an autopsy of the patient showed an isolated abscess of the ascending aorta without evidence of infective endocarditis, coronary artery rupture, aortic aneurysm, or aortic dissection making this an unusual case of cardiac tamponade. The aim of this case report is to encourage providers to obtain a tissue culture of any aortic abscesses so that the organisms involved can be identified. The identification of such organisms may help guide antimicrobial treatment in similar presentations in the future.

An unusual blunt force trauma pattern and mechanism to the cranial vault: Investigation of an atypical infant homicide.

This case report presents an unusual fracture pattern in the cranium of a four-month-old infant indicative of child abuse. Upon postmortem examination, the infant presented with numerous bilateral linear cranial fractures running perpendicular to the sagittal suture with depressed and curvilinear fractures apparent on the supra-auricular surfaces of the cranium. Histological evidence indicates multiple traumatic events to the cranium. In addition, the stair-step pattern of a parietal fracture may represent multiple contiguous fractures from repeated loading of the head at different times with variation of the focal points of compressive force. Additionally, the left humerus, left radius, and left ulna have healing metaphyseal fractures, and the left ulna also has an antemortem diaphyseal fracture which resulted in the distal metaphysis being rotated 45 degrees medially. Integration of autopsy, anthropological, and neuropathological reports for this case suggest multiple inflicted injury episodes with a repeated atypical mechanism(s) to the cranial vault of the infant. During investigative interviews, the caretaker admitted to squeezing the infant's head and neck on multiple occasions to quiet the child. This reported abusive mechanism is consistent with the pattern of symmetric cranial fractures and soft tissue injuries indicating asphyxiation. This case report provides forensic investigators with a potential trauma mechanism to explore in cases when a similar pattern of cranial trauma is observed and highlights the need for greater research on fracture propagation and fracture healing in the infant cranium.

A comparison of three decalcification agents for assessments of cranial fracture histomorphology.

The extraction of mineral calcium from bone by decalcification is a critical step in the preparation of histological samples for light microscopy. This study assessed the time required for complete decalcification and the resultant histomorphological preservation of bone histomorphology by three decalcification agents: 7% hydrochloric acid (HCl), 5% nitric acid, and 10% ethylenediaminetetraacetic acid (EDTA). The goal of this study was to identify which decalcification agent provides the optimal combination of expedient processing and quality histological outcomes of cranial fracture samples. HCl provided the most rapid decalcification ( X ¯  = 3.57 days), nitric acid followed closely ( X ¯  = 10.35 days), while EDTA took significantly longer on average ( X ¯  = 78.97 days) but encompassed a broader range of times. Decalcification agent, sample thickness, sample width, and decedent age are significant predictors of decalcification time. Sample visualization quality, measured for tissues, cells, and nuclei on a five-point Likert scale, was highest for samples decalcified in 10% EDTA, second highest using 5% nitric acid, and lowest for 7% HCl. The quality difference between EDTA and nitric acid was not highly significant for any of the three features. For basic assessments of bone histomorphology, the study results indicate 5% nitric acid is suitable for the decalcification of adult specimens and samples thicker than 3 mm. EDTA is a suitable agent for thin samples of the cranial vault (<3 mm) from infants and young children less than three years old, decalcifying samples in a timeframe comparable to nitric acid while providing the best quality and clarity of samples.

A Case of Lethal Abdominal Compartment Syndrome due to Rapidly Expanding Ovarian Small Cell Carcinoma Pulmonary Type.

A 53-year-old woman presented with a rapidly growing pelvic mass suspected to be endometrial cancer due to endometrial biopsy showing grade 1 endometrioid adenocarcinoma. Due to severe aortic valve stenosis, she underwent a transcatheter aortic valve replacement (TAVR) for surgical optimization for a planned total abdominal hysterectomy, bilateral salpingo-oophorectomy, and tumor debulking. She was discharged on dual antiplatelet therapy with plans for future surgery, but was readmitted with abdominal distension, constipation, and urinary retention. The pelvic mass seen on prior imaging studies had increased in size. Unanticipated asystole cardiac arrest occurred two days after readmission, which on autopsy was found to be secondary to abdominal compartment syndrome from a rapidly enlarging ovarian small cell carcinoma pulmonary type.

Homicides Disguised as Staged Suicides.

Determining the correct cause and manner of death are among the chief responsibilities of the forensic pathologist. When confronted with a case having a questionable manner of death, it is important for scene evidence, witness statements, and forensic autopsy findings to be thoroughly reviewed before certifying the manner of death. Herein three gunshot wound cases are presented which initially were suspected to be suicides but were instead determined to be homicides through full investigations with correlation to autopsy findings.

Case of polycythemia vera concurrent with FIP1L1-PDGFRA-positive myeloproliferative neoplasm with eosinophilia.

We report an unusual case of a symptomatic patient who initially had high hemoglobin and low serum erythropoietin levels, fitting a clinical diagnosis of polycythemia vera. However, after treatment with hydroxyurea and serial phlebotomies had been started, the patient developed hypereosinophilia, fitting the category of a myeloproliferative neoplasm with eosinophilia associated with the FIP1L1-PDGFRA gene fusion, as confirmed by molecular analysis. We discuss the clinical presentation, evolution, response to treatment, and pathogenetic implications of this case.