Acute inflammatory response to contrast agent aspiration and its mechanisms in the rat lung.

OBJECTIVES/HYPOTHESIS: Contrast agent (CA) aspiration is an established complication of upper gastrointestinal and videofluoroscopic swallow studies. The underlying molecular biological mechanisms of acute response to CA aspiration in the respiratory organs remain unclear. The aims of this study were to elucidate the histological and biological influences of three kinds of CAs on the lung and to clarify the differences in acute responses. STUDY DESIGN: Animal model. METHODS: Eight-week-old male Sprague Dawley rats were divided into five groups (n = 6 in each group). Three groups underwent tracheal instillation of one of three different CAs: barium (Ba) sulfate, nonionic contrast agents (NICAs), and ionic contrast agents (ICAs). A control group was instilled with saline and a sham group was instilled with air. All animals were euthanized on day 2 after treatment and histological and gene analysis was performed. RESULTS: No animal died after CA or control/sham aspiration. Ba caused severe histopathologic changes and more prominent inflammatory cell infiltration in the lungs compared with the two other iodinated contrast agents. Increases in expressions of inflammatory cytokines (tumor necrosis factor [Tnf], interleukin-1ß [Il1b], and interferon-γ [Ifng]) were observed in Ba aspiration rats, and upregulation of Il1b was seen in ICA aspiration rats. NICA did not cause obvious histologic changes or expressions of inflammatory cytokines and fibrosis-related genes in the lungs. CONCLUSIONS: Ba caused significantly more acute lung inflammation in a rodent model than did ioinic and nonionic iodinated CAs. Nonionic contrast did not cause any discernible inflammatory response in the lungs, suggesting that it may be the safest contrast for videofluoroscopic swallow studies. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1533-1538, 2019.

Fatal zolpidem poisoning due to its intravenous self-injection: Postmortem distribution/redistribution of zolpidem and its predominant metabolite zolpidem phenyl-4-carboxylic acid in body fluids and solid tissues in an autopsy case.

We experienced a curious fatal case, in which a male in his 20s self-administered zolpidem intravenously. The victim was found dead lying on floor of his apartment room, with a tourniquet band and new injection marks on his right forearm. Nearby the body, a medical disposal syringe containing small-volume solution dissolving crushed zolpidem tablets was found. The postmortem interval was estimated at about two days. The direct cause of his death was judged as asphyxia due to the aspiration of stomach contents into the trachea and bronchi. The specimens dealt with were body fluids and solid tissues including femoral vein blood, right and left heart blood, pericardial fluid, urine, bile, stomach contents, the brain, lung, heart muscle, liver, spleen, kidney, pancreas and skeletal muscle. For the extractions of zolpidem, zolpidem phenyl-4-carboxylic acid, deuterated internal standards zolpidem-d7 and zolpidem phenyl-4-carboxylic acid-d4, a modified QuEChERS method was used, followed by the analysis by liquid chromatography-tandem mass spectrometry. Because this study included various kinds of human matrices with quite different properties, the standard addition method was most preferable to overcome the matrix effects and recovery rates, and also did not need to use blank human matrices for validation experiments. The concentration of zolpidem and its phenyl-4-carboxylic acid metabolite in various specimens tested were generally extreme higher than those of reported fatal cases, supporting that the victim had died of intravenous zolpidem injection. The concentrations of zolpidem in femoral vein blood and right and left heart blood specimens in the present case were 9.55, 28.5 and 46.9µg/mL, respectively, which far exceeded estimated fatal levels. The present study also showed the postmortem distribution/redistribution of zolpidem and its phenyl-4-carboxylic acid metabolite in 15 body fluid and solid tissue specimens including stomach contents. Although a number of published literatures dealt with zolpidem poisoning cases due to oral ingestion of the drug, this is the first report on fatal intravenous zolpidem injection case and postmortem distribution of zolpidem and its predominant metabolite.

The effect of preparative solid food status on the occurrence of nausea, vomiting and aspiration symptoms in enhanced CT examination: prospective observational study.

OBJECTIVE:: To evaluate the correlation between preparative solid food status and the incidence of nausea, vomiting and aspiration symptoms in contrast-enhanced CT examination, and to provide direction for standardizing the preparative dietary policies. METHODS:: Patients who underwent routine enhanced CT examination at our hospital between June 2015 and June 2017 (110,836 cases) were enrolled and allocated into solid food fasting group (51,807 cases) and solid food non-fasting group (59,029 cases). Fluids ingestion was not restricted for any case. The differences in the incidence of nausea, vomiting and aspiration symptoms between the two groups of patients with various basic data were compared. The risk factors for the occurrence of nausea, vomiting and aspiration symptoms were analyzed. RESULTS:: The total incidence of nausea and vomiting was extremely low (0.071%), and no aspiration developed. There was no significant difference in the incidence of nausea and vomiting between the two groups in all respects (p > 0.05). The incidence of nausea and vomiting in patients with an iodine adverse drug reaction (ADR) history was higher than those with other ADR history (p = 0.008) and those without ADR history (p = 0.001). CONCLUSION:: The occurrence of nausea and vomiting has no correlation with the preparative solid food status. Unless compulsory in clinical needs and constraints and gastrointestinal examination, solid food fasting is not a must in other examinations. Particular attention should be paid to the patients with an iodine ADR history in an effort to prevent possible ADRs. ADVANCES IN KNOWLEDGE:: The correlation between preparative solid food status and the incidence of nausea, vomiting and aspiration symptoms in contrast-enhanced CT examination were comprehensively analyzed in a large-scale population.

A case report and literature review of barium sulphate aspiration during upper gastrointestinal examination.

RATIONALE: Even though barium sulphate aspiration during upper gastrointestinal examination is a well-known phenomenon, complication such as long-term lung injury and death may still occur. This may depend upon the concentration, amount, anatomy, or certain predisposing factors. PATIENT CONCERNS: A 47-year-old woman who had a barium swallow to screen for foreign body in esophagus. DIAGNOSES: Chest radiographs demonstrated massive barium sulphate depositions in her trachea and inferior lobe of right lung. INTERVENTIONS: A chest x-ray was done that revealed massive barium sulphate depositions in her trachea and lower lobe of right lung. As the patient did not have further complaints, she requested a transfer to West China Hospital of Sichuan University, the hospital being near her residence, for further treatment. She eventually recovered and was discharged after 1 week. OUTCOMES: There were 23 articles (22 English and 1 Chinese with 17 men and 11 women) included in the study. The risk factors of barium sulphate aspiration are dysphagia (10/28, 35.71%) followed by esophageal obstruction caused by tumor (5/28, 17.86%) and foreign body in esophagus (3/28, 10.71%). Infants (5/28, 17.86%) are also one of the high-risk population. Both the lungs were affected in most of the patients (21/28, 75%). Majority of the presentation in patients (21/28, 75%) were dyspnea, hypoxemia, acute respiratory distress syndrome (ARDS), or respiratory failure. Few patients (7/28, 25%) showed no symptoms or mild symptoms such as cough and fever. Barium sulphate aspiration can be life-threatening with a high risk of death (nearly 40%). LESSONS: When performing an upper gastrointestinal examination with barium sulphate, careful consideration of concentration and amount of barium sulphate and that of risk factors should be undertaken so as to avoid life-threatening aspiration.

Safety of Target-Controlled Propofol Infusion by Gastroenterologists in Patients Undergoing Endoscopic Resection.

BACKGROUND: A target-controlled infusion (TCI) of a propofol system uses a pharmacokinetic model to achieve and maintain a selected target blood propofol concentration. The aim of this study was to assess whether the propofol TCI system could be safely used by gastroenterologists in patients undergoing endoscopic resection including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) compared with a manually controlled infusion (MCI) system. METHODS: A total of 431 patients undergoing therapeutic endoscopy (178 ESD and 253 EMR) were consecutively included from November 2011 to August 2014. The patients were divided into the MCI (271) and TCI (160) propofol infusion groups. We compared adverse event rates in MCI and TCI groups and assessed independent risk factors for adverse events. RESULTS: The total sedation-related adverse event rate was 5.8 % (25/431). Most of the events were minor, and the rate of major events was 0.5 % (2/431). There was no significant difference in adverse event rate between the MCI and TCI groups [5.5 % (15/271) vs. 6.3 % (10/160); P = 0.759]. In univariate analysis, the propofol infusion time was significantly associated with adverse events (94.88 vs. 59.45 min, P = 0.017). In the multivariate analysis, there were no significant factors associated with adverse events. TCI was not an independent risk factor for adverse events despite the fact that the TCI had a longer duration of infusion and higher total infusion dose (95 % CI, 0.343-2.216; P = 0.773). CONCLUSIONS: TCI of propofol by gastroenterologists may provide safe sedation in patients undergoing ESD and EMR under careful respiratory monitoring.

Oropharyngeal aspiration of bleomycin: An alternative experimental model of pulmonary fibrosis developed in Swiss mice.

OBJECTIVE: Pulmonary fibrosis (PF) is a progressive and predominantly lethal form of several interstitial lung diseases with limited current therapeutics; it is, therefore, essential to develop a simple, homogeneous, and noninvasive disease model to investigate possible anti-fibrotic approaches. The present study is designed to develop oropharyngeal aspiration (OPA) model of bleomycin (BLM)-induced PF as a simple and alternative to intratracheal (IT) administration of BLM in Swiss mice strain. MATERIALS AND METHODS: Mice were divided into two groups, BLM-treated and normal control. BLM via OPA (2 IU/kg) was used to induce PF. Water for injection was used as a vehicle in control animals. Body weights were measured once in a week, and the study was continued for 21 days. At the end of the study, animals were euthanized and bronchoalveolar lavage fluid was collected and subjected to lymphocytes count, estimation of albumin and protein levels. Lung tissues were collected, and various biochemical assays (malondialdehyde, glutathione, nitric oxide, hydroxyproline) and molecular techniques including ELISA and Western blot were performed to investigate the effect of OPA-BLM. Further, histopathology and Masson's trichrome staining techniques were performed in lung sections. RESULTS: OPA administration of BLM in Swiss mice significantly induced PF, evident from lung index and morphology. Several oxidative stress parameters and hydroxyproline assay revealed the significant (P < 0.05) induction of PF. Further results obtained from histopathology, Masson's trichrome staining, ELISA, and Western blot confirmed the significant induction of PF via OPA-BLM. CONCLUSION: BLM administration by OPA route in Swiss mice can be used as a simple, homogeneous, and noninvasive model of inducing PF and to investigate the effect of various anti-fibrotic agents as an alternative to IT-BLM.

Metal rich particulate matter impairs acetylcholine-mediated vasorelaxation of microvessels in mice.

BACKGROUND: Exposure to PM2.5 (particulate matter<2.5 µm) has been associated with changes in endothelial function. PM2.5 was collected from two Chinese cities, Jinchang (JC) and Zhangye (ZH), both with similar PM2.5 concentrations. However, JC had levels of nickel (Ni), selenium (Se), copper (Cu), and arsenic (As) that were 76, 25, 17, and 7 fold higher than that measured in ZH, respectively. We used this unique PM sample to delineate the chemical components that drive pulmonary and systemic effects and explore the mechanism(s) by which vascular dysfunction is caused. METHODS: Male FVB/N mice received oropharyngeal aspiration of water or PM2.5 from JC, ZH or ZH spiked with one of the following elements at the same concentrations found in the JC PM (Ni=4.76; As=2.36; Se=0.24; Cu=2.43 µg/mg) followed by evaluation of markers of pulmonary and systemic inflammation. Mesenteric arteries were isolated for gene expression or functional response to various agonists (Phenylephrine, Acetylcholine, and Sodium Nitroprusside) and inhibitors (L-NAME, Apocynin, and VAS2870) ex vivo. RESULTS: Protein and total cell counts from lung lavage revealed significant pulmonary inflammation from ZH (p<0.01) and JC and ZH+NiSO4 (p<0.001) as compared to control and a significant decrease in mesenteric artery relaxation (p<0.001) and this decrease is blunted in the presence of NADPH oxidase inhibitors. Significant increases in gene expression (TNF-α, IL-6, Nos3; p<0.01; NOX4; p<0.05) were observed in JC and ZH+NiSO4, as well as significantly higher concentrations of VEGF and IL-10 (p<0.01, p<0.001; respectively). CONCLUSIONS: Our results indicate that the specific toxicity observed in PM from JC is likely due to the nickel component in the PM. Further, since VAS2870 was the most successful inhibitor to return vessels to baseline relaxation values, NADPH Oxidase is implicated as the primary source of PM-induced O2•-.

The Role of Phosphorylated Cx43 on PKC Mediated Ser368 in Lung Injury Induced by Seawater Inhalation.

Seawater aspiration may result in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which is characterized by pulmonary inflammation and lung edema that closely related to pulmonary barrier dysfunction and intracellular communication. The aim of the present research was to explore the role of connexion 43 (Cx43) in seawater aspiration-induced ALI/ARDS. The results from in vivo experiments showed that seawater inhalation led to increased expression of p-PKC and phosphorylated Cx43 (p-Cx43), which were followed by protein rich fluid leakage and TNF-α and IL-1ß secretion. Besides, the results from in vitro tests proved that the expression of p-PKC directly influenced phosphorylation state of Cx43 and its function, which could further affect the inflammatory factors secretion and intercellular communication. In conclusion, seawater aspiration causes p-Cx43 expression by PKC pathway, which is involved in the on come and development of pulmonary inflammation and lung edema.

Analysis of carbonated thin liquids in pediatric neurogenic dysphagia.

BACKGROUND: Aspiration of liquids is a serious complication of neurological impairments such as traumatic brain injury or stroke. Carbonated liquids have been examined as a possible alternative to thickened liquids to help reduce aspiration in cases of dysphagia in adults, but no published literature to the best of our knowledge has evaluated this technique in children. If carbonated liquids result in safer swallowing in children, they could provide a preferred alternative to thickened liquids. OBJECTIVE: This pilot study examined whether carbonated thin liquids (CARB) improved swallowing compared to non-carbonated thin liquids (NOCARB) for children with neurogenic dysphagia. MATERIALS AND METHODS: Twenty-four children admitted to a level I trauma center for acute neurological injury/disease were evaluated via videofluoroscopic swallow studies. Four descriptive outcome measures were contrasted. RESULTS: CARB significantly decreased pooling (P = 0.0006), laryngeal penetration/aspiration (P = 0.0044) and Penetration-Aspiration Scale scores (P = 0.0127) when compared to NOCARB. On average, CARB improved scores on the Penetration-Aspiration Scale by 3.7 points for participants who aspirated NOCARB. There was no significant difference in pharyngeal residue noted between CARB and NOCARB (P = 0.0625). CONCLUSION: These findings support the hypothesis that carbonated thin liquids may provide an alternative to thickened liquids for children with neurogenic dysphagia. Implications for future research and clinical practice are discussed.

Characterizing risk factors for pediatric lamp oil product exposures.

UNLABELLED: Poisonings from lamp oil ingestion continue to occur worldwide among the pediatric population despite preventive measures such as restricted sale of colored and scented lamp oils. This suggests that optimal prevention practices for unintentional pediatric exposures to lamp oil have yet to be identified and/or properly implemented. OBJECTIVE: To characterize demographic, health data, and potential risk factors associated with reported exposures to lamp oil by callers to poison centers (PCs) in the US and discuss their public health implications. STUDY DESIGN: This was a two part study in which the first part included characterizing all exposures to a lamp oil product reported to the National Poison Data System (NPDS) with regard to demographics, exposure, health, and outcome data from 1/1/2000 to 12/31/2010. Regional penetrance was calculated using NPDS data by grouping states into four regions and dividing the number of exposure calls by pediatric population per region (from the 2000 US census). Temporal analyses were performed on NPDS data by comparing number of exposures by season and around the July 4th holiday. Poisson regression was used to model the count of exposures for these analyses. In the second part of this project, in order to identify risk factors we conducted a telephone-based survey to the parents of children from five PCs in five different states. The 10 most recent lamp oil product exposure calls for each poison center were systematically selected for inclusion. Calls in which a parent or guardian witnessed a pediatric lamp oil product ingestion were eligible for inclusion. Data on demographics, exposure information, behavioral traits, and health were collected. A descriptive analysis was performed and Fisher's exact test was used to evaluate associations between variables. All analyses were conducted using SAS v9.3. RESULTS: Among NPDS data, 2 years was the most common patient age reported and states in the Midwestern region had the highest numbers of exposure calls compared to other regions. Exposure calls differed by season (p < 0.0001) and were higher around the July 4th holiday compared to the rest of the days in July (2.09 vs. 1.89 calls/day, p < 0.002). Most exposures occurred inside a house, were managed on-site and also had a "no effect" medical outcome. Of the 50 PC-administered surveys to parents or guardians, 39 (78%) met inclusion criteria for analysis. The majority of ingestions occurred in children that were 2 years of age, that were not alone, involved tiki torch fuel products located on a table or shelf, and occurred inside the home. The amount of lamp oil ingested did not appear to be associated with either the smell (p = 0.19) or the color of the oil (p = 1.00) in this small sample. Approximately half were asymptomatic (n = 18; 46%), and of those that reported symptoms, cough was the most common (n = 20, 95%) complaint. CONCLUSIONS: Lamp oil product exposures are most common among young children (around 2 years of age) while at home, not alone and likely as a result of the product being in a child-accessible location. Increasing parental awareness about potential health risks to children from these products and teaching safe storage and handling practices may help prevent both exposures and associated illness. These activities may be of greater benefit in Midwestern states and during summer months (including the period around the July 4th holiday).

Elemental mercury toxicity due to aspiration following intentional massive ingestion.

Deliberate poisoning with intentional ingestion of elemental mercury is reported not to result in systemic toxicity due to minimal absorption from the gastrointestinal tract. We report a case of a 43 year old male who intentionally ingested 200 ml elemental mercury which resulted in abdominal pain and vomiting. The patient subsequently aspirated globules of mercury which was confirmed on chest x-ray and his blood mercury levels were markedly raised. He was treated with chelating agents and managed in a negative pressure room to reduce the risk of staff being exposed to exhaled mercury vapour from the patient.

Can we safely avoid fasting before abortions with low-dose procedural sedation? A retrospective cohort chart review of anesthesia-related complications in 47,748 abortions.

BACKGROUND: Some licensing authorities require fasting before abortions under intravenous sedation to avoid aspiration of gastric contents. This study was conducted to estimate the incidence of anesthesia-related complications in women undergoing abortions without preprocedure fasting. STUDY DESIGN: This is a retrospective cohort chart review of patients having abortions with both fentanyl and midazolam at two urban free-standing abortion clinics with routine policy of advising women to eat a light meal before the procedure. RESULTS: There were no reports of anesthesia-related complications in the 47,748 charts reviewed from 1998 to 2010. Applying Hanley's formula for rare events that have not occurred, the upper 95% confidence interval for the true incidence of anesthesia-related complications for women having abortion under low-dose procedural sedation without fasting was estimated to be 0.00006%. CONCLUSIONS: This large retrospective cohort chart review identified no complications related to low-dose procedural sedation in over 47,000 consecutive nonfasting patients having abortions through 18 weeks' gestation. Eliminating the requirement to fast would decrease unnecessary stress and unpleasant symptoms without increase in the anesthesia-related complications for women having abortions.

Emergency physician-administered propofol sedation: a report on 25,433 sedations from the pediatric sedation research consortium.

STUDY OBJECTIVE: We describe the adverse events observed in a large sample of children sedated with propofol by emergency physicians and identify patient and procedure characteristics predictive of more serious adverse events. METHODS: We identified sedations performed by emergency physicians using propofol as the primary sedative, included in the Pediatric Sedation Research Consortium database from July 2004 to September 2008. We describe the characteristics of the patients, procedures, location, adjunctive medications, and adverse events. We use a multivariable logistic regression model to identify predictors of more serious adverse events. RESULTS: Of 25,433 propofol sedations performed by emergency physicians, most (76%) were performed in a radiology department. More serious adverse events occurred in 581 sedations (2.28%; 95% confidence interval 2.1% to 2.5%). There were 2 instances of aspiration, 1 unplanned intubation, and 1 cardiac arrest. Significant predictors of serious adverse events were weight less than or equal to 5 kg, American Society of Anesthesiologists classification greater than 2, adjunctive medications (benzodiazepines, ketamine, opioids, or anticholinergics), nonpainful procedures, and primary diagnoses of upper respiratory illness or prematurity. CONCLUSION: We observed a low adverse event prevalence in this largest series of propofol sedations by emergency physicians. Factors indicating greater risk of more serious adverse events are detailed.

Accidental death from hydromorphone ingestion.

A 15-year-old male orally consumed an unknown but fatal amount of sustained release hydromorphone. He was naïve to opioid use. No other drugs or alcohol were involved. The cause of death was acute aspiration-related bronchopneumonia, secondary to hydromorphone ingestion; the manner of death was accidental. Hydromorphone and hydromorphone-3-glucuronide were quantified in postmortem fluids by tandem liquid chromatography-mass spectrometry. The hydromorphone concentrations in the peripheral blood, urine, and vitreous humor were 57, 4460, and 31 ng/mL, respectively. The hydromorphone-3-glucuronide concentrations in the corresponding three fluids were 459, 36,400, and 40 ng/mL. Hydromorphone-3-glucuronide accumulation probably did not contribute significantly to the opiate toxicity. The proposed minimum lethal hydromorphone blood concentration in the nontolerant user is in the vicinity of 60 ng/mL.